Insecticide and process for preparing active component

(54) An insecticidal composition and a process for the manufacture of an active ingredient

An insecticidal composition, characterized in that it contains at least one heterocyclic compound of the formula I as active ingredient, in which n is 12 3 4, the number 0 or 1, R, R, R and R are independently hydrogen or methyl, R is hydrogen or methyl, X is sulfur, or -NR? or -СН_Э'Y'² 9 represents a nitrogen atom or a -CR group and Z represents a 5- to 6-membered heterocyclic group containing 1 to 3 heteroatoms selected from oxygen, sulfur and nitrogen, at least one of which is nitrogen and which is optionally substituted. The active compounds of formula (I) are prepared by reacting compounds of formula (VII) with compounds of formula (VIII) in the optional presence of inert solvents and in the presence of acid binding agents.

<img file="CS255867B2_D0001.tif" />

(VII)

The present invention relates to an insecticidal composition comprising the novel heterocyclic compound as an active ingredient. The invention further relates to a process for the preparation of these novel heterocyclic compounds.

It is already known that certain nitromethylenderivatives such as 1-benzyl-2-nitromethylenetetrahydropyrimidine (cf. DE-OS 2 514 402) have an insecticidal effect. It is further known that certain thiazolidine derivatives have an antitumor effect against tumors of the gastrointestinal tract (cf. Japanese Patent Application Publication No. 196 877/1984).

In addition, in Can. J. Chem., Vol. 39, pp. 1787-1796, discloses 1-benzyl-2-nitroiminoimidazolidine.

It has now been found that the novel heterocyclic compounds of formula (I)

<img file="CS255867B2_D0002.tif" />

(I) in which

<img file="CS255867B2_D0003.tif" />

means 0 or 1,

3 4

R, R, R and R are each independently hydrogen or methyl, is hydrogen or methyl, is sulfur, oxygen or

I -NR

I or -CH₂, whereas

-t

R represents a hydrogen atom, a C 1 -C 3 alkyl group, an allyl group, an acetyl group, a methylsulfonyl group, a dimethylaminocarbonyl group, a phenoxycarbonyl group, a benzoyl group optionally substituted with a chlorine atom; an ethoxycarbonyl group, a benzyl group optionally substituted by chlorine, -O-ethyl-S. -n-propylthiolophosphono or -CH₂-W or -CO-W where.

W represents a 5- to 6-membered heterocyclic radical containing 1 or 2 heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, at least one of which is a nitrogen atom optionally substituted by a chlorine atom and / or a methyl group,

Y represents an atom in which q

R is atoms

1 g of nitrogen or = CR, hydrogen, halogen, C 1 -C 1 alkylcarbonyl, benzoyl optionally substituted by methyl; ethoxycarbonyl, phenylsulfonyl, phenoxycarbonyl, phenylthio or phenylsulfonylaminocarbonyl, and

Z is a 5- to 6-membered heterocyclic group containing 1 to 3 heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, at least one of which is a nitrogen atom and optionally substituted with at least one substituent selected from the group consisting of: it consists of a fluorine atom, a chlorine atom, a bromine atom, a trifluoromethyl group, a methyl group, an ethyl group, a cyano group, a methoxy group, a methylthio group and a trifluoroethoxy group, that when, R @ 1, R @ 2 and simultaneously represent hydrogen atoms, X is -NH and Y is = CH, then Z is not a pyridyl group, they exhibit significant insecticidal properties.

Accordingly, the present invention provides an insecticidal composition characterized in that it contains at least one compound of the formula I as active ingredient.

<img file="CS255867B2_D0004.tif" />

(I) in which the number is 0 or 1,

R¹, R, R^J and R^q each independently represents a hydrogen atom or a methyl group,

R is

X is wherein

R is hydrogen, C 1 -C 3 alkyl, allyl, acetyl, methylsulfonyl, dimethylaminocarbonyl, phenoxycarbonyl, benzoyl optionally substituted with chloro; an ethoxycarbonyl group, a benzyl group optionally substituted by chlorine, -O-ethyl-Sn-propylthiolophosphono or -CH₂“W or -CO-W, where

W is a 5- to 6-membered heterocyclic radical containing 1 or 2 heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, at least one of which is optionally substituted by chlorine and / or methyl, atom atom hydrogen or methyl, sulfur, oxygen or -NR⁷ or a group -CH3-9

Y represents a nitrogen atom or a group = CR, in which g

R represents a hydrogen atom, a halogen atom, an alkylcarbonyl group having 1 to 3 carbon atoms in the alkyl portion, a benzoyl group optionally substituted by a methyl group; ethoxycarbonyl, phenylsulfonyl, phenoxycarbonyl, phenylthio or phenylsulfonylaminocarbonyl means a 5- to 6-membered heterocyclic group containing 1 to 3 heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, at least one of which is and optionally substituted with at least one substituent selected from the group consisting of fluorine, chlorine, bromine, trifluoromethyl, methyl, ethyl, cyano, methoxy, methylthio and trifluoroethoxy, provided that when R, R, R and R are both hydrogen, X is -NH and Y is = CH then Z it is not a pyridyl group.

Included within the scope of the compounds of Formula I are compounds of Formula Ia (Ia) wherein n, R 1 is a compound of formula Ia¹, R², R², R⁴, R, R⁹ and Z are as defined above,

X is a sulfur atom, an oxygen atom, or an -N-R6 group, wherein

R¹⁰ has the same meaning as R⁷ with the exception of the acetyl group, the methylsulfonyl group and the -O-ethyl-Sn-propylthiolophosphono group.

The novel compounds of the general formula (Ia) are prepared by reacting

(a) to compounds of formula II

<img file="CS255867B2_D0005.tif" />

(II) wherein n, R¹, R², R², R⁴, R, χΐ and Z are as defined above, with compounds of formula III

R'- SR⁹^WITHС = C - NO - (III),

R in which

R 'is lower alkyl or benzyl or R' optionally forms a ring together with the two sulfur atoms to which they are attached,

Q

R is as defined above, optionally in the presence of inert solvents;

b) treating compounds of formula II with compounds of formula IV

R (Hal)₂C

C - no₂ (IV) in which:

Hal is a halogen atom and

R represents a hydrogen atom, a halogen atom or a lower alkyl group, optionally in the presence of inert solvents and in the presence of acid-binding agents, or

c) treating compounds of formula II with compounds of formula V

R

I (Hal)₃C-CH-NO₂ (V) in which

Hal and R have the meanings given above, optionally in the presence of inert solvents and in the presence of acid binding agents.

The compounds of formula (I) are also within the scope of the compounds of formula (Ib)

<img file="CS255867B2_D0006.tif" />

n-no₂ (Ib) wherein n, R¹, R², R³, R1, R2, x¹ and Z are as defined above.

Compounds of formula (Ib) are prepared by:

d) treating the compounds of the above formula II with nitroguanidines of the formula

<img file="CS255867B2_D0007.tif" />

N °₂ optionally in the presence of an inert solvent.

The compounds of formula (I) are also within the scope of the compounds of formula (I)

<img file="CS255867B2_D0008.tif" />

(Ic) wherein n, R¹, R², R³, R⁴X, R and Z are as defined above.

Compounds of formula Ic are prepared by:

e) compounds of formula VI

<img file="CS255867B2_D0009.tif" />

(VI), in which n, R¹, R², R³, R⁴x, R and Z are as defined above, in reaction with fuming nitric acid, optionally in the presence of an inert solvent.

The compounds of formula (I) according to the invention are prepared by the formation of compounds of formula (VII)

П⁴ .R³ \ / _R2

HN ^ X

Ϊ y-no₂ wherein n, R¹, R², R³, R⁴X and Y are as defined above, with compounds of formula VIII

R

Z - CH - M (VIII), in which:

R and Z are as defined above, and

M represents a halogen atom or a group of formula -OSC 4 T, wherein

T represents an alkyl group, a phenyl group or a tolyl group, optionally in the presence of inert solvents and in the presence of acid binding agents.

This process will also be referred to as process f).

. As already mentioned, the novel heterocyclic compounds have significant insecticidal properties.

Surprisingly, the novel heterocyclic compounds of the present invention exhibit substantially higher and much superior insecticidal activity than the prior art compounds.

In addition, the heterocyclic compounds of the present invention exhibit a remarkable insecticidal activity against harmful insects, particularly sucking insects, represented by insects of the order Hemoptera, such as aphids, lamps and crisps, resistant to insecticides based on organic phosphates and carbamates due to prolonged use.

Particularly preferred compounds of formula I are the following:

3- (2-chloro-5-pyridylmethyl) -2- (nitromethylene) tetrahydro-2H-1,3-thiazine,

3- (2-chloro-5-pyridylmethyl) -2- (nitromethylene) thiazolidine,

3- (2-fluoro-5-pyridylmethyl) -2- (nitromethylene) tetrahydro-2H-1,3-thiazine;

3- (2-fluoro-5-pyridylmethyl) -2- (nitromethylene) thiazolidine,

3- (2-bromo-5-pyridylmethyl) -2- (nitromethylene) tetrahydro-2H-1,3-thiazine,

3- (2-bromo-5-pyridylmethyl) -2- (nitromethylene) thiazolidine,

3f (2-Methyl-5-pyridylmethyl) -2- (nitromethylene) thiazolidine

3- (2-methyl-5-pyridylmethyl) -2- (nitromethylene) tetrahydro-2H-1,3-thiazine,

3- (2-Trifluoromethyl-5-pyridylmethyl) -2- (nitromethylene) tetrahydro-2H-1,3-thiazine,

3- (3-pyridylmethyl) -2- (nitromethylene) thiazolidine,

3- (3-pyridylmethyl) -2- (nitromethylene) tetrahydro-2H-1,3-thiazine,

3- (2-Trifluoromethyl-5-pyridylmethyl) -2- (nitromethylene) thiazolidine

1- (5-pyrazolylmethyl) -2- (nitromethylene) imidazolidine,

1- (5-chloro-1-methyl-3-pyrazolylmethyl) -2- (nitromethylene) imidazolidine,

1- (1-methyl-4-pyrazolylmethyl) -2- (nitromethylene) tetrahydropyrimidine,

1- (1-methyl-4-pyrazolylmethyl) -2- (nitromethylene) imidazolidine

1- (3-Trifluoromethyl-5-isoxazolylmethyl) -2- (nitromethylene) tetrahydropyrimidine

1- (3-methyl-5-isoxazolylmethyl) -2- (nitromethylene) imidazolidine

1- (3-methyl-5-isoxazolyl-ethyl) -2- (nitromethylene) tetrahydropyrimidine,

1- (5-Isoxazolylmethyl) -2- (nitromethylene) imidazolidine

1- (2-methyl-5-thiazolylmethyl) -2- (nitromethylene) imidazolidine

1- (2-chloro-5-thiazolylmethyl) -2- (nitroniethylene) tetrahydropyrimidine,

1- (2-Trifluoromethyl-5-thiazolylmethyl) -2- (nitromethylene) imidazolidine

1- (1,2,5-thiadiazol-3-ylmethyl) -2- (nitromethylene) tetrahydropyrimidine,

1- (1,2,3-thiadiazol-5-ylmethyl) -2- (nitromethylene) tetrahydropyrimidine,

1- (2-methyl-5-thiazolylmethyl) -2- (nitromethylene) tetrahydropyrimidine,

1- (2-chloro-5-thiazolylmethyl) -2- (nitromethylene) imidazolidine,

1- (1,2,5-thiadiazol-3-ylmethyl) -2- (nitromethylene) imidazolidine,

1- (5-thiazolylmethyl) -2- (nitromethylene) tetrahydropyrimidine,

1- (5-pyrimidinyl) -2- (nitromethylene) imidazolidine

1- (2-methyl-5-pyrimidinylmethyl) -2- (nitromethylene) imidazolidine,

1- (2-pyrazinylmethyl) -2- (nitromethylene) imidazolidine,

1- (2-methyl-5-pyrazinylmethyl) -2- (nitromethylene) imidazolidine,

1- (2-chloro-5-pyrimidinylmethyl) -2- (nitromethylene) tetrahydropyrimidine,

1- (2-chloro-5-pyrimidinylmethyl) -2- (nitromethylene) imidazolidine,

1- (2-fluoro-5-pyrimidinylmethyl) -2- (nitromethylene) imidazolidine,

1- (2-Trifluoromethyl-5-pyrimidinylmethyl) -2- (nitromethylene) imidazolidine

1- (2-chloro-5-pyrazinylmethyl) -2- (nitromethylene) imidazolidine,

1- [1- (2-fluoro-5-pyrimidinyl) ethyl] -2- (nitromethylene) imidazolidine,

1- (2-chloro-5-pyridylmethyl) -2- (nitroimino) tetrahydropyrimidine,

1- (2-chloro-5-pyridylmethyl) -2- (nitroimino) imidazolidine

1- (2-Trifluoromethyl-5-pyridylmethyl) -2- (nitroimino) tetrahydropyrimidine

1- (2-Trifluoromethyl-5-pyridylmethyl) -2- (nitroimino) imidazolidine

1- (2-fluoro-5-pyridylmethyl) -2- (nitroimino) imidazolidine,

1- (2-bromo-5-pyridylmethyl) -2- (nitroimino) imidazolidine,

1- (2-methyl-5-pyridyimethyl) -2- (nitroimino) imidazolidine,

1- (2-chloro-5-pyridylmethyl) -2- (nitromethylene) pyrrolidine,

1- (2-chloro-5-thiazolylmethyl) -2- (nitroimino) tetrahydropyrimidine,

1- (2-chloro-5-pyrimidinylmethyl) -2- (nitroimino) imidazolidine,

1- (2-chloro-5-pyridylmethyl) -4-methyl-2- (nitromethylene) imidazolidine

1- (2-chloro-5-pyridylmethyl) -3- (3-pyridylmethyl) -2- (nitromethylene) imidazolidine, 1- (2-chloro-5-pyridylmethyl) -2- (bromonitromethylene) imidazolidine,

1- (2-chloro-5-pyridylmethyl) -2- (1-nitro-2-oxopentylidene) imidazolidine, ethyl-nitro [α- (2-chloro-5-pyridylmethyl) thiazolidin-2-ylidene] acetate; ;

1-acetyl-3- (2-chloro-5-pyridylmethyl) -2- (nitroimino) imidazolidine; . .

3- (2-ethyl-5-pyridylmethyl) -2- (nitromethylene) thiazolidine,

1- (2-methoxy-5-pyridylmethyl) -2- (nitroimino) imidazolidine a

N-phenylsulfonyl-nitro- [1- (2-chloro-5-pyridylmethyl) -imidazolidin-2-ylidene] -acetamide.

When variant (a) uses N- (1-methyl-4-pyrazolylmethyl) trimethylenediamine and 1-nitro-2,2-bis (methylthio) ethylene as the starting materials, the reaction of this variant can be illustrated by the following reaction. by the scheme:

h₂n- (ch₂)₃-nh-ch₂

<img file="CS255867B2_D0010.tif" />

(ch₃with)₂c = chno₂

<img file="CS255867B2_D0011.tif" />

<img file="CS255867B2_D0012.tif" />

chno₂ ch₃

<img file="CS255867B2_D0013.tif" />

ch₃

If, for example, 2- (2-methyl-5-pyrazinylmethylamino) ethanethiol and 2, 2-dichloronitroethane are used as starting materials in process variant (b), the reaction scheme can be illustrated as follows:

<img file="CS255867B2_D0014.tif" />

CH₂—NH - CH₂ —CH₂ - SH

-h CI₂C = CH-NO₂

<img file="CS255867B2_D0015.tif" />

<img file="CS255867B2_D0016.tif" />

If, for example, 2- (2-chloro-5-thiazolylmethylamino) ethanethiol and 1,2,2,2-tetrachloro-1-nitroethane are used as starting materials in process variant (c), the reaction scheme can be illustrated as follows:

<img file="CS255867B2_D0017.tif" />

4- ci₃c— chci_no₂

<img file="CS255867B2_D0018.tif" />

Cl

If, for example, N- (2-chloro-5-pyridylmethyl) trimethylenediamine and nitroguanidine are used as starting materials in process variant d), the following reaction scheme illustrates the reaction sequence:

Cl

<img file="CS255867B2_D0019.tif" />

ch₂nh- (CH₂)₃-nh₂

<img file="CS255867B2_D0020.tif" />

<img file="CS255867B2_D0021.tif" />

<img file="CS255867B2_D0022.tif" />

If, for example, 1- (2-chloro-5-pyridylmethyl) -2-iminoimidazolidine and fuming nitric acid are used as starting materials in process variant (e), the reaction scheme can be illustrated as follows:

<img file="CS255867B2_D0023.tif" />

HNO3

<img file="CS255867B2_D0024.tif" />

If, for example, 2-nitromethylenthiazolidine and 2-chloro-5-pyridylmethyl chloride are used as starting materials in the process according to the invention (according to variant f), the reaction scheme can be illustrated as follows:

<img file="CS255867B2_D0025.tif" />

Formula II includes generally defined compounds that are used as starting materials in the process of variant a), wherein n, R, R, RR, R, Z and

X¹ are as defined above.

The compounds of formula (II) used in the process of the invention include both known and novel compounds.

Known compounds are described, for example, in Japanese published patent application

Nos. 26 020/1984, 72 966/1984 and 132 943/1984, in Z. Anorg. allgem. Chem., Vol. 312, pp. 282-286, in Chim. Geterocykl. Soedin., 1974, No. 1, pp. 122-123, Methods Poluch. Khim. Reactivon Prep., No. 17, pp. 172-173, Issled. Obl. Geterocycl. Soedin., 1971, pp. 39-44, U.S. Patent No. 4,018,931, Arch. Pharm., 1982, Vol. 315, pp. 212-221, Methods Poluch. Khim. Reactivon Prep., 1967, pp. 133-134 and Ref. obščij Chimii, sv. 33, pp. 1,130-1,135.

Examples are:

N- (2-chloro-5-pyridylmethyl) -2-aminoethanethiol,

N- (2-chloro-5-pyridylmethyl) -3-aminopropanethiol,

N- (2-bromo-5-pyridylmethyl) -2-aminoethanethiol,.

N- (2-bromo-5-pyridylmethyl) -3-aminopropanethiol,

N- (2-fluoro-5-pyridylmethyl) -2-aminoethanethiol,

N- (2-fluoro-5-pyridylmethyl) -3-aminopropanethiol,

N- (1j) (2-chloro-5-pyridyl) ethyl] -2-aminoethanethiol,

N- (2,3-dichloro-5-pyridylmethyl) -2-aminoethanethiol,

N- (3-chloro-2-fluoro-5-pyridylmethyl) -2-aminoethanethiol,

N- (2-chloro-4-pyridylmethyl) -2-aminoethanethiol,

N- (3-chloro-2-pyridylmethyl) -2-aminoethanethiol,

N- (5-chloro-2-pyridylmethyl) -3-aminopropanethiol,

N- (3,5-dichloro-2-pyridylmethyl) -2-aminoethanethiol,

N- (5-fluoro-2-pyridylmethyl) -3-aminopropanethiol,

N- (6-bromo-2-pyridylmethyl) -2-aminoethanethiol,

N- (2-chloro-3-pyridylmethyl) -3-aminopropanethiol,

N- (5-chloro-3-pyridylmethyl) -3-aminopropanethiol,

N- (5-bromo-3-pyridylmethyl) -2-aminoethanethiol,

N- (5-fluoro-3-pyridylmethyl) -2-aminoethanethiol,

N- [1- (2-fluoro-5-pyridyl) ethyl] -2-aminoethanthiol,

N- (2,4-dichloro-5-pyridylmethyl) -3-aminopropanethiol,

N- (2,4-dibromo-5-pyridylmethyl) -2-aminoethanethiol,

N- (2,6-difluoro-4-pyridylmethyl) -2-aminoethanethiol,

N- (2-fluoro-4-pyridylmethyl) -3-aminopropanethiol,

N- (2,6-dibromo-4-pyridylmethyl) -2-aminoethanethiol,

N- (3-bromo-2-fluoro-5-pyridylmethyl) -2-aminoethanethiol,

N- (2-chloro-3-fluoro-5-pyridylmethyl) -2-aminoethanethiol, m.p.

N-pL- (2-chloro-5-pyridyl) propyl-2-aminoethanethiol,

N- (3-pyridylmethyl) 2-aminomethanethiol,

N- (3-pyridylmethyl) -3-aminopropanethiol,

N- (4-pyridylmethyl) -2-aminoethanethiol,

N- (4-pyridylmethyl) -3-aminopropanethiol,

N- (2-methyl-5-pyridylmethyl) -2-aminoethanthiol

N- (2-methyl-5-pyridylmethyl) -3-aminopropanethiol,

N- (2-chloro-3-methyl-5-pyridylmethyl) -2-aminoethanethiol,

N- [1- (3-pyridyl) ethyl] -3-aminopropanethiol,

N- (2-Trifluoromethyl-5-pyridylmethyl) -2-aminoethanthiol

N- (2-trifluoromethyl-5-pyridylmethyl) -3-aminopropanediol,

N- (2-trichloromethyl-5-pyridylmethyl) -2-aminoethanethiol,

N- (2-difluoromethyl-5-pyridylmethyl) -2-aminoethanethiol,

N- (4-pyrimidinylethyl) ethylenediamine,

N- (2-methyl-4-pyrimidinylmethyl) ethylenediamine,

N- (5-pyrimidinylmethyl) ethylenediamine,

N- (2-methyl-5-pyrimidinylmethyl) ethylenediamine,

N- (2,4,6-trichloro-5-pyrimidinylmethyl) ethylenediamine,

N- (pyrazinylmethyl) ethylenediamine,

N- [1- (pyrazinyl) ethyl] ethylenediamine,

N- (2-methyl-5-pyrazinylmethyl) ethylenediamine,

N- (3-pyridazinylmethyl) ethylenediamine,

N- (2-chloro-4-pyrimidinylmethyl) ethylenediamine,

N- (4-chloro-6-pyrimidinylmethyl) ethylenediamine,

N- (4-methyl-6-pyrimidinylmethyl) trimethylenediamine,

N- (2-fluoro-5-pyrimidinylmethyl) ethylenediamine,

N- (1- (2-chloro-5-pyrimidinyl) ethyl) ethylenediamine,

N- (2-chloro-5-pyrimidinylmethyl) ethylenediamine,

N- (2-chloro-5-pyrimidinylmethyl) trimethylenediamine,

N- (2-chlorodifluoromethyl-5-pyridinylmethyl) ethylenediamine,

N- (2-Trifluoromethyl-5-pyrimidinylmethyl) ethylenediamine

N- (2-bromodifluoromethyl-5-pyrimidinylmethyl) ethylenediamine,

N- (2-chloro-5-pyrazinylmethyl) ethylenediamine,

N- (2-Trifluoromethyl-5-pyrazinylmethyl) ethylenediamine

N- (3-fluoro-6-pyridazinylmethyl) ethylenediamine,

N- (3-methyl-6-pyridazinylmethyl) trimethylenediamine,

N- (4-pyridazinylmethyl) ethylenediamine,

N- (3-chloro-6-pyridazinylmethyl) ethylenediamine,

N- (4-pyridazinylmethyl) trimethylenediamine,

N- (3-trifluoromethyl-6-pyridazinylmethyl) ethylenediamine,

N- (1,3,5-triazin-2-ylmethyl) ethylenediamine,

N- (3-chloro-1,2,4-triazin-6-ylmethyl) ethylenediamine,

N- (3,5-dichloro-1,2,4-triazin-6-ylmethyl) ethylenediamine,

N- (3-chloro-1,2,4,5-tetrazin-6-ylmethyl) ethylenediamine,

N- (3-furylmethyl) ethylene (or -trimethylene) diamine,

N- (furfuryl) ethylene (or -trimethylene) diamine,

N- (5-methylfurfuryl) ethylene) or -trimethylene) diamine_r

N- (2-thienylmethyl) ethylene (or -trimethylene) diamine,

N- (4-imidazolylmethyl) ethylene (or -trimethylene) diamine,

N- (4-methyl-5-imidazolylmethyl) ethylene (or -trimethylene) diamine,

N- (tetrahydrofurfuryl) ethylene (or -trimethylene) diamine,

N- (5-methyltetrahydrofurfuryl) ethylene (or trimethylene) diamine,

N- (3-thienylmethyl) ethylene (or -trimethylene) diamine,

N- (2-pyrrolylmethyl) ethylene (or -trimethylene) diamine,

N- (1-methyl-2-pyrrolylmethyl) ethylene (or -trimethylene) diamine,

N- (5-methyl-2-thienylmethyl) ethylene (or -trimethylene) diamine,

N- (5-bromo-2-thienylmethyl) ethylene (or -trimethylene) diamine,

N- (5-trifluoromethylthio-2-thienylmethyl) ethylene (or -trimethylene) diamine,

<img file="CS255867B2_D0026.tif" />

ethylene (or -trimethylene) diamine,

N- (5-methyl-3-isoxazolylmethyl) ethylene (or -trimethylene) diamine,

N- (5-isoxazolylmethyl) ethylene (or -trimethylene) diamine,

N- (4-isoxazolylmethyl) ethylene (or -trimethylene) diamine,

N- (3-methyl-5-isoxazolylmethyl) ethylene (or -trimethylene) diamine,

N- (3-methyl-5-isoxazolylmethyl) ethylene (or -trimethylene) diamine,

N- (3-trifluoromethyl-5-isoazazol-1-yl) ethylene (or-trimethylene) diamine,

N- (3-chloro-5-isoxazolyl) ethyl_? ') &lt;t by .1 h; (i-p-trimethylene) diamine,

N- (5-isothiazolomethyl) ethylene (or tri-mellene) diamine,

N- (5-pyrazole-1-meth-1) ethylene (or trimethyl-1-ene) diamine,

N- (4-pyrazolylmethyl) ethylene (or -trimethylene) diamine,

N- (1-Methyl-4-pyrazolomethyl) ethylene (or-trimethylene) diamine

N- [1- (1-methyl-4-pyrazclyl) ethyl] ethylene (or -trimethylene) diamine,

N- [1- (2,2,2-trifluroethyl) -5-pyrazolylmethyl] ethylene (or -trimethylene) diamine,

N- (3-methyl-5-pyrazolylmethyl) ethylene (or -trimethylene) diamine,

N- (3-chloro-2-methyl-5-pyrazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2,3,5-trimethyl-4-pyrazolylmethyl) ethylene (or -trimethylene) diamine,

N- (5-oxazolymethyl) ethylene (or -trimethylene) diamine,

N- (4-methyl-5-oxazolylmethyl) ethylene (or -trimethylene) diamine,

N- (4-thiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (5-thiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2-methyl-5-thiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2-chloro-4-thiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2-chloro-5-thiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2-trifluoromethyl-5-thiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2-bromo-5-thiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2,4-dichloro-5-thiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (4-imidazolylmethyl) ethylene (or -trimethylene) diamine,

N- (1-methyl-2-imidazolylmethyl) ethylene (or -trimethylene) diamine,

N- (1,2,4-triazol-5-ylmethyl) ethylene (or -trimethylene) diamine,

N- (1-methyl-1,2,4-triazol-3-ylmethyl) ethylene (or-trimethylene) diamine,

Ν- (1,2,5-thiadiazol-4-ylmethyl) ethylene (or -trimethylene) diamine,

N- (1,2,3-thiadiazol-5-ylmethyl) ethylene (or -trimethylene) diamine,

N- (3-methyl-1,2,4-oxadiazol-5-ylmethyl) ethylene (or trimethylene) diamine,

N- (1,3-dioxolan-2-ylmethyl) ethylene (or -trimethylene) diamine,

N- (2,2-dimethyl-1,3-dioxolan-4-ylmethyl) ethylene (or-trimethylene) diamine,

N- (2-methyl-2-oxazolin-5-ylmethyl) ethylene (or -trimethylene) diamine,

N- (2-trifluoromethyl + 2-oxazolin-5-ylmethyl) ethylene (or -trimethylene) diamine,

N- (3-pyrrolylmethyl) ethylene (or -trimethylene) diamine,

N- (1-methyl-3-pyrrolylmethyl) ethylene (or -trimethylene) diamine,

N- (5-methyl-3-thienyl) ethylene (or-trimethylene) diamine,

N- (1-methyl-3-pyrrolylmethyl) ethylene (or -trimethylene) diamine,

N- (5-methyl-3-thienyl) ethylene (or-trimethylene) diamine,

N- (5-methyl-3-pyrrolylmethyl) ethylene (or -trimethylene) diamine,

N- (1,5-dimethyl-3-pyrrolyrmethyl) ethylene (or -trimethylene) diamine,

N- (2,5-dimethyl-3-furylmethyl) ethylene (or -trimethylene) diamine,

N- (2,5-dimethyl-3-thienylmethyl) ethylene (or-trimethylene) diamine,

N- (5-fluoro-3-furylmethyl) ethylene (or -trimethylene) diamine,

N- (4-chlorofurfuryl) ethylene (or -trimethylene) diamine,

N- (5-chlorofurfuryl) ethylene (or -trimethylene) diamine,

N- (5-chloro-3-furylmethyl) ethylene (or -trimethylene) diamine,

N- (5-chloro-3-thienylmethyl) ethylene (or -trimethylene) diamine,

N- (5-chloro-1-methyl-3-pyrrolylmethyl) ethylene (or -trimethylene) diamine, N- (5-bromo-3-furylmethyl) ethylene (or -trimethylene) diamine,

N- (5-trifluoromethylfurfuryl) ethylene (or -trimethylene) diamine,

N- (5-difluoromethylfurfuryl) ethylene (or -trimethylene) diamine,

N- (5-trifluoromethyl-3-thienylmethyl) ethylene (or -trimethylene) diamine,

N- (1-methyl-5-trifluoromethyl-3-pyrrolylmethyl) ethylene (or-trimethylene) diamine,

N- (3-isoxazolylmethyl) ethylene (or -trimethylene) diamine,

N- (4-isoxazolylmethyl) ethylene (or -trimethylene) diamine,

N- (3-fluoro-5-isoxazolylmethyl) ethylene (or -trimethylene) diamine,

N- (3-bromo-5-isoxazolylmethyl) ethylene (or -trimethylene) diamine,

N- (3-difluoromethyl-5-isoxazolyl) ethylene (or -trimethylene) diamine,

N- (3-chloromethyl-5-isoxazolylmethyl) ethylene (or -trimethylene) gives the amine,

N- (3-trichloromethyl-5-isoxazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2,5-dimethyl-4-isoxazolylmethyl) ethylene (or -trimethylene) diamine,

N- (3-isothiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (4-isothiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (3-pyrazolylmethyl) ethylene (or -trimethylene) diamine,

N- (1-methyl-3-pyrazolylmethyl) ethylene (or -trimethylene) diamine,

N- (1-methyl-5-pyrazolylmethyl) ethylene (or -trimethylene) diamine,

N- (3-chloro-1-methyl-2-pyrazolylmethyl) ethylene (or -trimethylene) diamine,

N- (5-trifluoromethyl-3-pyrazolylmethyl) ethylene (or -trimethylene) diamine,

N- (1-methyl-5-trifluoromethyl-3-pyrazolylmethyl) -ethylene (or -trimethylene) diamine,

N- (1-methyl-3-trifluoromethyl-5-pyrazolylmethyl) -ethylene (or -trimethylene) diamine,

N- (4-oxazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2-methyl-4-oxazolylmethyl) ethylene) or -trimethylene) diamine,

N- (2-methyl-5-oxazolylmethyl) -ethylene (or -trimethylene) diamine,

N- (2-fluoro-5-oxazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2-chloro-5-oxazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2-trifluoromethyl-5-oxazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2,4-dimethyl-5-oxazolylmethyl) ethylene (or -trimethylene) diamine,

N- [1- (5-thiazolyl) ethyl] ethylene (or -trimethylene) diamine,

N- (2-methyl-4-thiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (4-methyl-5-thiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2-fluoro-4-thiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2-fluoro-5-thiazolylmethyl) ethylene (or -trimethylene) diamine,

Nf 1- (2-chloro-5-thiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2-chloromethyl-5-thiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2-difluoromethyl-5-thiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2-trifluoromethyl-5-thiazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2-imidazolylmethyl) ethylene (or -trimethylene) diamine,

N- (1-methyl-5-imidazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2-fluoro-4-imidazolylmethyl) ethylene (or -trimethylene) diamine,

N- (2-chloro-4-imidazolylmethyl) ethylene (or -trimethylene) diamine,

N- (1,2-dimethyl-4-imidazol-2-ylmethyl) ethylene (or-trimethylene) diamine,

N- (1-methyl-2-trifluoromethyl-4-imidazolylmethyl) ethylene (or -trimethylene) diamine,

N- (1-methyl-1,2,3-triazol-4-ylmethyl) ethylene (or-trimethylene) diamine,

N - [(1-methyl-1,2,3-triazol-4-yl) ethyl-ethylene (or-trimethylene) diamine,

N- (3-methyl-1,2,4-triazol-5-ylmethyl) ethylene (or trimethylene) diamine,

N- (3-trifluoromethyl-1,2,4-triazol-5-ylmethyl) ethylene (or -trimethylene) diamine,

N- (1,2,4-oxadiazol-5-ylmethyl) ethylene (or-trimethylene) diamine,

N- (1,3,4-oxadiazol-2-ylmethyl) ethylene (or -trimethylene) diamine,

N- (1,2,3-oxadiazol-5-ylmethyl) ethylene (or -trimethylene) diamine,

N- (3-trifluoromethyl-1,2,4-oxadiazol-5-ylmethyl) ethylene (or -trimethylene) diamine,

N- (2-methyl-1,3,4-oxadiazol-5-ylmethyl) ethylene (or-trimethylene) diamine,

N- (2-trifluoromethyl-1,3,4-oxadiazol-5-ylmethyl) ethylene (or -trimethylene) diamine,

N- [2- (2,2,2-trifluoromethyl) -1,3,4-oxadiazol-5-ylmethyl] ethylene (or -trimethylene diamine,

N- (1,2,4-thiadiazol-5-ylmethyl) ethylene (or -trimethylene) diamine,

N- (1,2,3-thiadiazol-4-ylmethyl) ethylene (or -trimethylene) diamine,

N- [1- (1,2,3-thiadiazol-5-yl) ethyl] ethylene (or-trimethylene) diamine,

N- (1,3,4-thiadiazol-2-yl) ethylene (or -trimethylene) diamine,

N- (1,2,5-thiadiazol-3-ylmethyl) ethylene (or -trimethylene) diamine,

N- (3-methyl-1,2,4-thiadiazol-5-yl) ethylene (or trimethylene) diamine,

N- (4-methyl-1,2,3-thiadiazol-5-ylmethyl) ethylene (or-trimethylene) diamine,

N- (2-methyl-1,3,4-thiadiazol-5-ylmethyl) ethylene (or-trimethylene) diamine,

N- (2-trifluoromethyl-1,3,4-thiadiazol-5-ylmethyl) ethylene (or -trimethylene) diamine,

N- (2-fluoro-1,3,4-thiadiazol-5-ylmethyl) ethylene (or-trimethylene) diamine,

N- (2-chloro-1,3,4-thiadiazol-5-ylmethyl) ethylene (or-trimethylene) diamine,

N- (3-chloro-1,2,5-thiadiazol-4-ylmethyl) ethylene (or-trimethylene) diamine,

N- (3-tetrahydrothienylmethyl) ethylene (or -trimethylene) diamine,

N - [1- (3-tetrahydrothienyl) ethyl-ethylene (or-trimethylene) diamine,

N- (1-methyl-3-pyrrolidinylmethyl) ethylene (or -trimethylene) diamine,

N- (1,3-oxathiolan-2-ylmethyl) ethylene (or -trimethylene) diamine,

N- (1,3-dioxolan-4-ylmethyl) ethylene (or trimethylene) diamine.

N- (1,3-oxothiolan-4-ylmethyl) ethylene (or -trimethylene) diamine,

N- (1,3-dithiolan-4-ylmethyl) ethylene (or -trimethylene) diamine,

N- (thiazolidin-5-ylmethyl) ethylene (or -trimethylene) diamine,

N- (4-methyl-1,3-dioxolan-2-ylmethyl) ethylene (or-trimethylene) diamine,

N- (2-methyl-1,3-oxathiolan-4-ylmethyl) ethylene (or-trimethylene) diamine,

N- (2-chloromethyl-1,3-dioxolan-4-ylmethyl) ethylene (or-trimethylene) diamine,

N- (2-trifluoromethyl-1,3-dioxolan-4-ylmethyl) ethylene (or -trimethylene) diamine,

N- (3-thiolan-2-ylmethyl) ethylene (or -trimethylene) diamine,

N- (2-isoxazolin-5-ylmethyl) ethylene (or-trimethylene) diamine,

N- (3-methyl-2-oxazolin-5-ylmethyl) ethylene (or -trimethylene) diamine,

N- (3-trifluoromethyl-2-isoxazolin-5-ylmethyl) ethylene (or-trimethylene) diamine,

N - 3- (2,2,2-trifluoroethyl) -2-isoxazolin-5-ylmethyl] ethylene (or-trimethylene) diamine,

N- (2,4-dimethyl-2-oxazolin-4-ylmethyl) ethylene (or -trimethylene) diamine,

N- (2-methyl-2-thiazolin-4-ylmethyl) ethylene (or -trimethylene) diamine,

N- (2-oxazolidinon-5-ylmethyl) ethylene (or trimethylene) diamine;

N- (3-methyl-2-thioxothiazolidin-5-ylmethyl) ethylene (or-trimethylene) diamine,

N- (3-chloro-1,2,4-oxadiazol-5-ylmethyl) ethylene (or -trimethylene) diamine

N- (5-chloro-2-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2-fluoro-5-pyridylmethyl) ethylene (or -trimethylene) diamine, *

N- (2-chloro-5-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2-chloro-3-methyl-5-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2-difluoromethyl-5-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (5-trifluoromethyl-2-pyridylmethyl) ethylene (or -trimethylene) diamine,

256867

N- (2-trifluoromethyl-5-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2-bromodifluoromethyl-5-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2-chlorodifluoromethyl-5-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (5-trifluoromethyl-2-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (5-methyl-2-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (6-methyl-2-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (4-methyl-2-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (3-chloro-2-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (3,5-Dichloro-2-pyridylmethyl) ethylene (or-trimethylene) diamine,

N- (5-fluoro-2-pyridylmethyl) ethylene (or -trimethylene) diamine;

N- (6-bromo-2-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (6-chloro-4-methyl-2-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (5-methyl-2-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2-methyl-5-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2-chloro-3-pyridylmethyl) ethylene (or -trimethylene) diamine,

N-5-chloro-3-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (5-bromo-3-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2-bromo-5-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (5-fluoro-3-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2-fluoro-5-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- [2-methyl-1- (2-fluoro-5-pyridyl) propyl] ethylene (or-trimethylene) diamine,

N- (2-chloro-6-methyl-3-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2,4-dichloro-5-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2,6-dichloro-3-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2,4-dibromo-5-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2,4-difluoro-5-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (4-chloro-2-fluoro-5-pyridylmethyl) ethylene (or trimethylene) diamine,

N- (6-chloro-2-methyl-3-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2-chloro-4-methyl-5-pyridylmethyl) ethylene (or -trimethylene) diamine,

О

N- (2,3-Dichloro-5-pyridylmethyl) &amp; lt; tb &amp; gt; (гНю - t г i methylene) diamine,

N- (2-chloro-4-pyridylmethyl) ethylene terebromethylene) diamine,

N- (2-fluoro-4-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2,6-dichloro-4-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2-methyl-4-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- [1- (2-chloro-4-pyridyl) ethyl [ethylene (or-trimethylene) diamine,

N- (2-chloro-6-methyl-4-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2,6-dimethyl-4-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2-bromo-4-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2,6-dibromo-4-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2,6-dichloro-4-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (3-chloro-2-fluoro-5-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (3-bromo-2-fluoro-5-pyridylmethyl) ethylene (or -trimethylene) diamine,

N- (2-chloro-3-fluoro-5-pyridylmethyl) ethylene (or -trimethylene) diamine,

2-amino-1- (4-pyridylmethylamino) propane,

2-amino-2-methyl- (3-pyridylmethylamino) propane,

N- (4-pyridylmethyl) -2,2-dimethyltrimethylenediamine,

2-amino-1- (2-chloro-5-pyridylmethylamino) propane,

N- (2-chloro-5-pyridylmethyl) -2-methyltrimethylenediamine,

N- (3-pyridylmethyl) -N'-methylethylenediamine,

N- (2-chloro-5-pyridylmethyl) -N'-methylethylene (or -trimethylene) diamine,

N- (2-fluoro-5-pyridylmethyl) -N'-isopropylethylenediamine,

N- (2-chloro-5-pyridylmethyl) -N'-benzylethylenediamine,

N- (2-chloro-5-pyridylmethyl) -1 '- (3-pyridylmethyl) ethylenediamine,

N- (2-chloro-5-pyridylmethyl) -1 '- (1-methyl-4-pyrazolylmethyl) ethylenediamine,

2-methyl-2- (2-methyl-5-pyridylmethylamino) ethanethiol, 1-methyl-2- (2-chloro-5-pyridylmethylamino) ethanethiol,

2- (4-pyridylmethylamino) ethanol,

2- (3-pyridylmethylamino) ethanol,

3- (2-Methyl-3-pyridylmethyl) propanol

2- (2-methyl-5-pyridylmethyl) ethanol,

2- (2-chloro-5-pyridylmethyl) ethanol

3- (2-Trifluoromethyl-5-pyridylmethyl) propanol

N- (1-methyl-4-pyrazolylmethyl) -2,2-dimethyltrimethylenediamine,

Ν, Ν'-bis- (5-methyl-2-furfuryl) ethylenediamine,

N- (3-methyl-5-isoxazolylmethyl) -1 '- (1-methyl-4-pyrazolylmethyl) ethylene (or-trimethylene) diamine,

2- (3-methyl-5-isoxazolylmethylmethylamino) ethanethiol,

3- (1-Isopropyl-4-pyrazolylmethylamino) propanethiol

2- (1,2,5-thiadiazol-3-ylmethylamino) ethanethiol,

2-) 2-trifluoromethyl-5-thiazolylmethylamino) ethanethiol,

2- (3-methyl-5-isoxazolylmethylamino) ethanol,

2- (4-isothiazolylmethylamino) ethanol,

2- (5-oxazolylmethylamino) ethanol,

2- (3-Trifluoromethyl-5-isoxazolylmethylamino) ethanol

2- (5-pyridinylmethylamino) ethanethiol,

2- (3-Trifluoromethyl-6-pyridazinylmethylamino) ethanethiol

2- (2-methyl-5-pyrazinylmethylamino) ethanethiol, L.

2- (3-pyrazinylmethylamino) ethanol,

2- (3-chloro-6-pyridazinylmethylamino) ethanol,

2-amino-1- (2-pyridinylmethyl) aminopropane,

N- (5-pyrimidinylmethyl) -1 '- (1-methyl-4-pyrazolylmethyl) ethylenediamine and

N- (3-chloro-6-pyridazinylmethyl) -N'-methylethylenediamine.

As mentioned above, formula II also includes the novel compounds.

Thus, the compounds of formula IIa are included in formula II.

Z - CH - NH - CH₂

<img file="CS255867B2_D0027.tif" />

(Ha) in which

<td>n,</td><td>12 3 4 R, R, R, R, R and Z are as defined above,</td>

<td>X²</td><td>represents an oxygen atom or an -NR group¹®, whereas . R¹⁰ has the above meaning,</td>

<td>whereas</td><td>these compounds of formula (II) and can be obtained by:</td>

g) treating the compounds of formula VIII above and defined with compounds of formula IX

H₂N -CH₂¹ 2 (C)_n ------ C -X '₃'1

R^JR (IX), wherein n, R¹, R², R³, R⁴ а X² are as defined above, optionally in the presence of inert solvents and in the presence of acid binding agents.

If, for example, pyrazinylmethyl chloride and ethylenediamine are used as starting materials in process g), the reaction can be illustrated as follows:

<img file="CS255867B2_D0028.tif" />

H₂N- (CH₂)₂-NH₂

<img file="CS255867B2_D0029.tif" />

The compounds of formula (II) may be obtained by:

h) to compounds of formula X.

Z - C - R (X) where

Z and R are as defined above, with compounds of formula XI

H, N - CH, ---- - (C)_n ----- С -X^XH (XI),

II

R^J R · in which

R¹, R², R³, R⁴, n а X¹ are as defined above, whereby the resulting compounds are reduced, optionally in the presence of inert solvents.

If, for example, 6-chloronicotinaldehyde and 3-aminopropanethiol are used as starting materials in process h), the reaction scheme can be illustrated as follows:

<td>Cl —— CH</td><td>H + h₂n- (ch₂)₃-sh -&gt; Cl —— CH ^ - ^Η·&gt;</td>

<img file="CS255867B2_D0030.tif" />

If, in addition, for example, 5-pyrimidinocarbone is used as starting material in process h); and ethylenediamine, the reaction can be illustrated by the following reaction scheme:

<img file="CS255867B2_D0031.tif" />

<img file="CS255867B2_D0032.tif" />

<img file="CS255867B2_D0033.tif" />

ch = n- (ch₂)₂—Nh₂ + (H)

<img file="CS255867B2_D0034.tif" />

ch₂-nh- (CH₂)₂-nh₂

Compounds of formula IIIa which are used as starting materials in the process

g) are the same as the starting materials used in process f) as described above.

Compounds of formula IX that include both known and novel compounds can be readily prepared by known methods.

Examples of compounds of formula IX include:

ethylenediamine and trimethylenediamine (cf. German Published Publication No. 2,732,660 and French Patent Publication No. 1,499,785).

Here it can also be mentioned

2-aminoethanol and 3-aminopropanol, which are well known organic chemistry compounds.

In addition, examples of compounds of Formula IX include

N-benzylethylene (or -trimethylene) diamine (cf. Japanese Published Patent Application No. 78 971/1985, German Published Patent No. 2,514,402, German Published Publication No. 2,732,660 and Japanese Published Patent Application No. 68,551) 1985);

N-substituted alkylethylene (or -trimethylene) diamines which correspond to ethylenediamines or trimethylenediamines of formula II above.

In the practice of process (g), the desired compounds of formula (II) are readily obtained by reacting compounds of formula (VII) with compounds of formula (IX) in inert solvents as described in process (a), which will be described in more detail below.

Process g) can be easily carried out using more than 1 mol, for example about 5 mol, of the compounds of formula IX per 1 mol of the compounds of formula VIII, at a reaction temperature in the range - for example 0 to 50 ° C.

Compounds of formula (X) which are used as starting materials in process (h) include, for the most part, the known compounds.

Examples are:

6-chloronicotiraldehyde,

6-bromonicotinaldehyde,

6-fluoronicotinaldehyde,

5,6-dichloronicotinaldehyde,

5-chloro-6-fluoronicotinaldehyde,

2-chloro-4-pyridylcarbaldehyde,

3-Chloro-2-pyridinecarbba dehyd,

3,5-dichloro-2-pyridinaldehyde,

5-fluoro-2-pyridinecarbaldehyde,

6-bromo-2-pyridinecarbaldehyde,

2-chloronicotinaldehyde,

5-chloronicotinaldehyde,

5-bromonicotinaldehyde,

5-fluoronicotinaldehyde,

4.6- dichlornicotinaldehyde,

4.6- dibromnicotinaldehyde,

2,6-difluoro-4-pyridinecarbaldehyde,

2-fluoro-4-pyridinecarbaldehyde,

2,6-dibromo-4-pyridinecarbaldehyde,.

5-bromo-6-fluoronicotinaldehyde,

6-chloro-5-fluoronicotinaldehyde,

2-chloro-5-propionylpyridine, nicotinaldehyde,

4-pyridinecarbaldehyde,

6-methylnicotinaldehyde,

6-chloro-4-methylnicotinaldehyde,

6-trifluoromethylthionicotinaldehyde,

4-pyrimidinecarbaldehyde,

2-methyl-4-pyrimidinecarbaldehyde,

5-pyrimidinecarbaldehyde,

2-methyl-5-pyridinecarbaldehyde,

2.4.6- trichloro-5-pyrimidinecarbaldehyde, pyrazylcarbaldehyde,

2-methyl-5-pyrazinecarbaldehyde,

3-pyridazinecarbaldehyde,

2-chloro-4-pyrimidinecarbaldehyde,

4-chloro-6-pyrimidinecarbaldehyde,

4-methyl-6-pyrimidinecarbaldehyde,

2-fluoro-5-pyrimidinecarbaldehyde,

2-chloro-5-pyrimidinecarbaldehyde,

2-Trifluoromethyl-5-pyrimidinecarbaldehyde,

2-chloro-5-pyrazinecarbaldehyde,

2-Trifluoromethyl-5-pyrazinecarbaldehyde

3-fluoro-6-pyridazinecarbaldehyde,

3-Methyl-6-pyridazinecarbaldehyde

4-pyridazinecarbaldehyde,

3-chloro-6-pyridazinecarbaldehyde,

3-Trifluoromethyl-6-pyridazinecarbaldehyde,

1.3.5-triazine-2-carbaldehyde,

3-chloro-1,2,4-triazine-6-carbaldehyde,

3,5-dichloro-1,2,4-triazine-6-carbaldehyde a

3-chloro-1,2,4,5-tetrazine-6-carbaldehyde.

The compounds of formula (X) may be prepared by various conventional methods. These methods will be described in particular below.

For example, pyridine carbaldehydes of formula (X) can be prepared by reacting the corresponding vinyl pyridines with agents used for ozonolysis (cf. J. org. Chem., Vol. 26, 4 912-4 914) and then converting according to British Patent Specification 2,004,368. 2-chloro-5-pyridylcarbonitrile to 6-chloronicotinaldehyde.

In addition, the compounds of formula (X) can generally be prepared without difficulty by the conventional method of reducing the corresponding carboxylic acids and their esters or by Vilsmeyer reaction.

For example, pyridine carbaldehydes can also be prepared by reducing the corresponding pyridine carboxylic acids and their esters (see Org. React., Vol. 8, 218-257).

Compounds of formula (X) may also be directly prepared by cyclization. For example, for 4-pyrimidinecarbaldehydes, the corresponding 2-methylthio-4-methyl-6-pyrimidinecarbaldehyde acetal is obtained by reacting diethoxyacetyl acetone with S-methylisothiourea. Subsequent reduction and treatment with hydrochloric acid gave 4-methyl-6-pyrimidinecarbaldehyde. The use of diethoxyacetylacetone derivatives in this reaction may lead to the synthesis of similar compounds such as 4-pyrimidinecarbaldehyde, 2-methyl-4-pyrimidinecarbaldehyde and 2-trifluoromethyl-4-pyrimidinecarbaldehyde (see Chem. Ber., Vol. 97, pp. 3 407-3). 417). Many known methods for the synthesis of 5-pyrimidinecarbaldehydes are known in the field of organic chemistry.

For example, 5-pyrimidinecarbaldehydes can be synthesized by introducing a 5-hydroxy-6-oxodihydropyrimidine formyl group via a Vilsmeyer reaction, halogenating the product to give 4,6-dichloro-5-formylpyrimidine, and then dehalogenating the title compound (cf. Liebigs Ann. Chem., Vol. 766, pp. 73-83, and Monatsh. Chem., Vol. 96, pp. 1567-1722). By applying this reaction, 2-alkylsubstituted and 2-haloalkylsubstituted 5-pyrimidinecarbaldehydes can be prepared. 5-pyrimidinecarbaldehydes which contain other substituents at the 2-position are described in Japanese Patent Application Publication No. 59 669/1984.

For example, 5-pyrimidinecarbaldehydes which contain, for example, an alkyl, alkoxy, alkylthio or alkylamino group at the 2-position, are obtained by reaction of (2-dimethylamino) methylene-propanediylidene (-bis-dimethylaminoperchlorate) (described in Collect. Czech. Chem. Comm., Vol. 30, page 2 125) with suitable amidine hydrochlorides.

With respect to 5-pyrimidinecarbaldehydes containing a halogen atom at the 2-position, for example, 2-chloro-5-pyrimidinecarbaldehyde can be prepared by chlorination of ethyl 2-oxo-1,2-dihydro-5-pyrimidinecarboxylate with phosphorus oxychloride to give ethyl- 2-chloro-5-pyrimidinecarboxylate (Chem. Pharm. Bull., Vol. 12, pp. 804-808; a similar example is given in J. Org. Chem., Vol. 29, pp. 1 740-1 743), and reducing the resulting compound in a conventional manner. When the chlorine atom in the 2-position is active, it can be converted to another substituent, such as

2-fluoro using potassium fluoride.

As regards pyridazinecarbaldehydes, 3- and 4-pyridazinecarbaldehydes are described on page 213 of Monatsh. Chem., Vol. 108, and methyl-substituted pyridazinecarbaldehydes are described in Heterocycl. Chem., Vol. 17, page 1 501.

In addition, as regards 5-membered heterocyclic carbaldehydes, the compounds are described separately below.

Fural is a known compound and can be easily produced by introducing a halogen atom into a furan ring. For example, 5-chlorofural and 4,5-dichlorofural can be prepared from fural (J. org. Chem., Vol. 11, pp. 1955-1958). 5-nitrofural is also an easy-to-use compound. 5-cyanfural is described in Tetrahedron, Vol. 39, p. 3881, and 5-phenoxyfural are described in Chem. Pharm. Bull., Vol. 28, No. 9, page 2,846. Other furanecarbaldehydes other than fural, especially methyl-substituted furals and other furanecarbaldehydes are also known compounds and can be readily prepared.

Thiophenecarbonylaldehyde is a known compound and a halogen atom can easily be introduced into the thiophene ring. For example, 2,3-dichloro-4-thiophenecarbaldehyde can be prepared from 3-thiophenecarbaldehyde (cf. Tetrahedron, Vol. 1, p. 403-1406). 2,3-dibromo-5-thiophenecarbaldehyde can be prepared from 2-thiocarbaldehyde (J. Org. Chem., Vol. 41, p. 2,835). Alkyl-substituted, especially methyl-substituted thiophenecarbaldehydes are also known compounds.

Pyrrolecarbaldehydes are known compounds, 1-methyl-2-pyrrolecarbaldehyde can be prepared from 1-methylpyrrole by Vilsmeyer reaction or methylation of 2-pyrrolecarbaldehyde (Beilstein, Vol. 21, I, p. 279). '

4-isothiazolecarbaldehydes can be prepared from 4-isothiazolylcarboxylic acid (cf.

J. Medicin. Chem., Vol. 13, p.112 (1818-1122), and 5-isothiazolecarbaldehyde can be prepared from 5-isothiazolyllithium (cf. J. Chem. Soc. 1964, pp. 446-451).

5-Pyrazolecarbaldehyde and 3-methyl-5-pyrazolecarbaldehyde can be prepared directly in cyclization (cf. Chem. Ber., Vol. 97, pp. 3 407-3 417). A similar method can be used to prepare 3-trifluoromethyl-5-pyrazolecarbaldehyde.

4-Methyl-5-imidazolecarbaldehyde and 1-methyl-5-imidazolecarbaldehyde are known compounds (J. Pharm. Soc. Japan, Vol. 60, pp. 184-188; JA_ CS, Vol. 71, pp. 2 444-2). 448).

Many substituted thiazolecarbaldehydes are known compounds (cf. Japanese Published Application No. 206370/1984; Chem. Ab., Vol. 62, 764d; Chem. Ber., Vol. 101, p. 3872). For example, 2-chlorothiazole-5-carbaldehyde can be prepared by lithiation with butyllithium and subsequent formylation; Substituted 1,3,4-thiadiazolecarbaldehydes are also known compounds (cf. Japanese Patent Application Publication No. 206 370/1984).

1,2,3-thiadiazole-5-carbaldehyde is also a known compound (cf.

No. 1,113,705) which are used as starting materials in the process

Compounds of Formula XI

h) include compounds of formula IX above.

In addition, 2-aminoethanethiol and 3-aminopropanethiol are cited as examples (cf. J. Org. Chem., Vol. 27, pp. 4 712-4 713) and^;may also include aminoalkanothiols. J.

. ‘ :....... 3 · ·

For example, in the case where X is:. carried out in the same manner as described: vJ 4 712-4 713; &lt;&lt;: &lt;

a sulfur atom; the above process h)

Óřg^:&lt;Chem. , Vol; 27, str. 2,452-2. 457 a

In process c), in the first step, thiazolidine or tetrahedrothiazines can be prepared in the form of intermediates by reaction of compounds of formula X with compounds of formula XI in the presence of an inert solvent such as benzene, and in a subsequent step with an agent such as sodium borohydride, lithium aluminum hydride, aluminum borohydride, potassium borohydride, etc. to give compounds of formula IIb. '

In the practice of process (h), thiazolidine or tetrahydrothiazines can be obtained not only as intermediates by distilling off the volatile fraction and following the first step reaction under reduced pressure, for example at a pressure of 133.3 Pa at 50-80 ° C, but also by direct reduction without isolation. .

When X 1 is -NR¹®, then in process h) the desired compound of formula IIb can be obtained by refluxing the starting materials in an inert solvent (such as benzene) and directly reducing the reaction mixture in a conventional manner without separating the Schiff base or imine intermediate as described below in the examples below.

In process h), preferably more than 1 mol, for example about 5 mol, of the compounds of formula XI is used per 1 mol of the compound of formula X, and the reaction is preferably carried out at atmospheric pressure, usually at 0 to 100 ° C.

In addition, as an alternative process for the preparation of compounds of formula II wherein X * is sulfur, a halogenation of compounds of formula II wherein X is¹ means an oxygen atom with halogenating agents such as thionyl chloride and subsequent reaction of the obtained compounds with potassium hydrogen sulphide.

The compounds of formula III which are used as starting materials in process (a) include both known and novel compounds.

Examples of known compounds include (cf., for example, Chem. Ber., Vol. 100, 591-604):

1-nitro-2,2-bis (methylthio) ethylene, 1-nitro-2,2-bis (ethylthio) ethylene,

1-nitro-2,2-bis (benzylthio) ethylene a

2-nitromethylene-1,3-dithiolane.

The above compounds can be prepared in a conventional manner by reacting nitromethane with carbon disulfide in the presence of a base and alkylating the resulting product.

If other nitroalkanes are used in place of nitromethane in the process, similar compounds of formula III can be readily prepared.

If, in addition to the nitromethane, acyl-substituted nitromethane is used instead of nitromethane, the desired compounds of formula III can be prepared.

If, for example, benzoylnitromethane is used, then 1-benzoyl-1-nitro-2,2-bis-methylthioethylene, i.e. the novel compound, is prepared, and if acetylnitromethane is used, 1-acetyl-1-nitro-2 is readily prepared. 2-bis (methylthio) ethylene, ie also a novel compound. ·

Compounds of formula (IV) which are used as starting materials in the process

b), are known compounds (cf. Chem. Abstr., Vol. 44, 1011F, Japanese Patent Application Laid-open No. 137 473/1984).

Examples of such compounds include:

2.2- dichloronitroethylene,

1.2.2- trichloronitroethylene,

1-fluoro-2,2-dichloronitroethylene, 1-methyl-2,2-dichloronitriethylene.

The compounds of formula V which are used as starting materials in process c) are known compounds (cf. J. Org. Chem., Vol. 25, 1312, ibid., Vol. 28, 1281- to 1283, Chem.). Ber., 75B, 1 323-1 330, Japanese Patent Application Publication No. 48 978/1985).

Examples of such compounds include:

2.2.2- trichloro-1-nitroethane,

1.2.2.2- tetrachloro-1-nitroethane,

2.2.2-trifluoro-1-nitroethane.

Compounds of formula (VI) are a general definition of compounds that are required as starting materials in process (e), wherein R¹, R², R³, R, X, R, Z and n are as defined above.

Compounds of formula VI include both known and novel compounds. For example

2-Imino-3- (4-pyridylmethyl) thiazolidine is described in J. Med. Chem., Vol. 22, 237-247.

Other compounds corresponding to formula VI can also be prepared in the same manner as described in the above-cited publication.

Compounds of formula (VI) may be prepared, for example, by reacting the above compounds of formula (II) with halogens.

Said reaction can be carried out easily by mixing the reactants with stirring in inert solvents, whereby the resulting products can be obtained in the form of hydrohalides.

Typical examples of compounds of formula VI (in the form of hydrohalides) include:

hydrobromides or hydrochlorides,

1- (2-chloro-5-pyridylmethyl) -2-iminoimidazolidine,

1- (2-chloro-5-pyridylmethyl) -2-iminotetrahydropyrimidine,

1- (2-fluoro-5-pyridylmethyl) -2-iminoimidazolidine,

1- (2-bromo-5-pyridylmethyl) -2-iminoimidazolidine,

1- (2-Trifluoromethyl-5-pyridylmethyl) -2-iminoimidazolidine.

1- (2-Methyl-5-pyridylmethyl) -2-iminoimidazolidine

1- (3-pyridylmethyl) -2-iminoimidazolidine a

1- (3-pyridylmethyl) -2-tetrahydropyrimidine.

Compounds of formula (VII) are a general definition of compounds that are required as starting materials in process (f), wherein n, R 1, R 2², R³, R1, X and Y are as defined above.

The compounds of formula VII are for the most part known compounds.

Examples of such compounds include:.

2-nitromethylenimidazolidine,

2-nitromethylenetetrahydropyrimidine,

4,4-dimethyl-2-nitromethylenimidazolidine,

3-Methyl-2-nitromethylenimidazolidine

2-nitromethylenthiazolidine,

2-nitromethylenetetrahydro-2H-1,3-thiazine,

2-nitromethylene-5-methylthiazolidine,

2-nitromethyleneoxazolidine,

2-nitromethylene-4-methyloxazolidine,

2-nitromethylenetetrahydro-2H-1,3-oxazine,

2-nitromethylenopyrrolidine,

2-nitromethylenepiperidine, ethyl-nitro (imidazolidin-2-ylidene) acetate,

2- (acetylnitromethylene) imidazolidine,

2- (benzoylnitromethylene) imidazolidine, ethyl-nitro (1-ethoxycarbonylimidazolidin-2-ylidene) acetate,

2- (2-dimethylamino-1-nitroethylidene) thiazolidine, ethyl nitro (tetrahydro-2H-1,3-thiazin-2-ylidene) acetate, phenyl nitro (tetrahydro-2H-1,3-thiazin-2-ylidene) )acetate,

2-acetylnitromethylenetetrahydro-2H-1,3-thiazine,

2-benzoylnitromethylenetetrahydro-2H-1,3-thiazine,

2-phenylthionithromethylenetetrahydro-2H-1,3-thiazine, ethyl nitro (oxazolidin-2-ylidene) acetate, ethyl nitro (tetrahydro-2H-1,3-oxazin-2-ylidene) acetate,

3-methyl-2-nitromethylenopyrrolidine, methyl-nitro (pyrrolidin-2-ylidene) acetate, ethyl-nitro (thiazolidin-2-ylidene) acetate,

2-nitroiminoimidazolidine,

4,4-dimethyl-2-nitroiminoimidazolidine,

2-nitroiminotetrahydropyrimidine,

3-Methyl-2-nitroiminoimidazolidine

2-nitroiminothiazolidine, ¹

2-nitroiminotetrahydro-2H-1,3-thiazine,

2-nitroiminoxazolidine,

4-methyl-2-nitroiminooxazolidine,.

2-nitroiminopyrrolidine,

2-nitroiminopiperidine,

3-Methyl-2-nitroiminopyrrolidine a

2-nitroiminotetrahydro-2H-1,3-oxazine.

The 2-nitromethylenimidazolidines (or tetrahydropyrimidines) of the above formula (VII) are well-known compounds (cf., for example, Chem. Ber., Vol. 100, 591-604, Belgian Patent No. 821,281, US Patent No. 3,971,774).

In addition, N-acyl derivatives can be prepared from 2-nitromethylenimidazolidines (or tetrahydropyrimidines) by known methods (cf. Japanese Published Patent Application Nos. 67 473/1985 and 61 575/1985).

In addition, for a group other than the nitro group which is bound to the methylene group of the 2-nitromethylenimidazolidines (or tetrahydropyrimidines), the compounds of formula (VII) may be prepared according to the known procedure described in U.S. Patent Nos. 3,996,372, 4,002,765 Nos. 4,042,696, 4,052,411, 4,053,619, 4,053,622 and 4,053,623, and Japanese Patent Application Publication No. 151,727 / 1977 and Belgian Patent Specification No. 821,282.

The 2-nitromethylenthiazolidines (or tetrahydro-2H-1,3-triazines) are also largely known compounds, which can be readily prepared, for example, by reaction of aminoalkanethioles with the aforementioned compounds of formula III, which can be replaced by the above compounds of formula IV or of formula V.

In addition, the 2-nitromethylenthiazolidines (or tetrahydro-2H-1,3-thiazines) position 2 can be substituted by various known methods to give starting materials of formula VII (cf. U.S. Patent Nos. 3,962,234, 4,022,775, No. 4,024,254, 4,044,128, 4,045,434, and 4,076,813 and Japanese Patent Application Publication No. 151,882 / 1975).

2-Nitromethylene oxazolidines (or -tetrahydro-2H-1,3-oxazines) are also known compounds that can be prepared by reacting aminoalkanols with the above compounds of formula III, which can be replaced by the above compounds of formula IV or V. (cf. Adv. Pestic Sci., Plenary Lect. Symp. Pap Int., Congr. Pestic. Chem., 4, 1978, 206-217 (referenced in Chem. Abstr., Vol. 91, 103 654), U.S. Pat. No. 3,907,790; 151 882/1975 and 151 727/1977).

2-Nitromethylene pyrrolidines (or piperidines) are also known compounds which can be prepared, for example, by reaction of 2-methoxypyrrolidines and nitroalkanes (cf. Dutch Patent Nos. 7,306,020 and 7,306,145).

The 2-nitroimino derivatives of the compounds of formula VII are also known compounds.

For example, 2-nitroiminooxazolidines are described in J. Am. Chem. Soc., Vol. 73, 2,213-2,216.

2-nitroiminoimidazolidines, 2-nitroiminotetrahydropyrimidines and their N-acetylderivatives are described in J. Am. Chem. Soc., Vol. 73, 2101-2205 and British Patent Specification No. 2,055,796.

N-acyl derivatives, with the exception of N-acetylderivatives, N-sulfonylderivatives, and N-phosphonoderivatives, are novel compounds which can be prepared in the same manner as described in British Patent Specification No. 2,055,796.

The 2-nitroiminothiazolidines (or tetrahydro-2H-1,3-thiazines, 2-nitroiminopyrrolidines or -piperidines), which can be prepared by reacting nitroguanidine with diamines, aminoalkanols or aminoalkanthiols, or by reacting the 2-imino derivative with nitric acid in the presence of sulfuric acid, disclose in the aforementioned British patent specification.

The compounds of formula (VIII) represent a general definition of the compounds required as starting materials in process (f), wherein Z and R are as defined above.

In formula VIII, Z and R preferably have the above-mentioned preferred meanings.

The compounds of formula VIII which are used as starting materials in the process of the invention include known compounds, for example those already described in J. Org. Chem., Vol. 34, 3547, J. Medicin. Chem., Vol. 14, 211-213 and 557-558, 1971, U.S. Pat. No. 4,332,944, MJ Heterocycl. Chem., 1979, Vol. 16, 333-337.

Examples of such compounds include:

3-Picolyl chloride

1- (3-pyridyl) ethyl chloride

4-picolyl chloride,

5-chloro-2-pyridylmethyl chloride,

2-fluoro-5-pyridylmethyl chloride,

2-chloro-5-pyridylmethyl chloride,

1- (2-chloro-5-pyridyl) ethyl chloride

2-chloro-3-methyl-5-pyridylmethyl chloride,

5-trifluoromethyl-2-pyridylmethyl chloride,

5-trifluoromethyl-2-pyridylmethyl chloride,

5-Methyl-2-pyridylmethyl chloride

6-methyl-2-pyridylmethyl chloride,

4-Methyl-2-pyridylmethyl chloride

5-ethyl-2-pyridylmethyl chloride,

4,6-dimethyl-2-pyridylmethyl chloride,

3-Chloro-2-pyridylmethyl chloride

3,5-dichloro-2-pyridylmethyl chloride,. 5-fluoro-2-pyridylmethyl chloride,

6-bromo-2-pyridylmethyl chloride,

6-chloro-4-methyl-2-pyridylmethyl chloride,

5-methyl-3-pyridylmethylmethylene chloride,

2-methyl-5-pyridylmethyl chloride,

2-chloro-3-pyridylmethyl chloride,

5-chloro-3-pyridylmethyl chloride,

5-bromo-3-pyridylmethyl chloride,

2-bromo-5-pyridylmethyl chloride,

5-fluoro-3-pyridylmethyl chloride,

2-fluoro-5-pyridylmethyl chloride,

1- (2-fluoro-5-pyridyl) ethyl chloride,

2-chloro-6-methyl-3-pyridylmethyl chloride,

2,4-dichloro-5-pyridylmethyl chloride,

2,6-dichloro-5-pyridylmethyl chloride,

2,4-dibromo-5-pyridylmethyl chloride,

2,4-difluoro-5-pyridylmethyl chloride,

4-chloro-2-fluoro-5-pyridylmethyl chloride,

6-chloro-2-methyl-3-pyridylmethyl chloride, 2-chloro-4-methyl-5-pyridylmethyl chloride,

2,3-dichloro-5-pyridylmethyl chloride, 2-chloro-4-pyridylmethyl chloride, 2-fluoro-4-pyridylmethylchloride, 2₁6-dichloro-4-pyridylmethyl chloride,

2,6-difluoro-4-pyridylmethyl chloride,

2-methyl-4-pyridylmethyl chloride,

1- (2-chloro-4-pyridyl) ethyl chloride

2-chloro-6-methyl-4-pyridylmethyl chloride,

2,6-dimethyl-4-pyridylmethyl chloride,

2-bromo-4-pyridylmethyl chloride,

2,6-dibromo-4-pyridylmethyl chloride,

3-Chloro-2-fluoro-pyridylmethyl chloride

3-bromo-2-fluoro-pyridylmethyl chloride,

2-chloro-3-fluoro-5-pyridylmethyl chloride,

3-furylmethyl chloride, furfuryl chloride,

5-Methylfurfuryl chloride

2-thienylmethyl chloride,

4-imidazolylmethyl chloride,

4-methyl-5-imidazolylmethyl chloride, tetrahydrofurfuryl chloride,

5-methyltetrahydrofurfuryl chloride,

3-thienylmethyl chloride,

2-pyrrolylmethyl chloride, 1-methyl-2-pyrrolylmethyl chloride,

5-methyl-2-thienylmethyl chloride, 5-bromo-2-thienylmethyl chloride,

1- (2-thienyl) ethyl chloride, 5-methyl-3-isoxazolylmethyl chloride, 5-isoxazolylmethyl chloride,

4-isoxazolylmethyl chloride,

3-methyl-5-isoxazolylmethyl chloride,

3-Trifluoromethyl-5-isoxazolylmethyl chloride,

3-chloro-5-isoxazolylmethyl chloride,

5-isothiazolylmethyl chloride, 5-pyrazolylmethyl chloride,

4-pyrazolylmethyl chloride, 1-methyl-4-pyrazolylmethyl chloride,

1- (1-methyl-4-pyrazolyl) ethyl chloride

3-methyl-5-pyrazolylmethyl chloride,

3-chloro-2-methyl-5-pyrazolylmethyl chloride, 2,3,5-trimethyl-4-pyrazolylmethyl chloride,

5-Oxazolylmethyl chloride

4-Methyl-5-oxazolylmethyl chloride

4-thiazolylmethyl chloride,

5-thiazolylmethyl chloride,

2-methyl-5-thiazolylmethyl chloride, 2-chloro-4-thiazolylmethyl chloride,

2-chloro-5-thiazolylmethyl chloride,

2-Trifluromethyl-5-thiazolylmethyl chloride

2-bromo-5-thiazolylmethyl chloride,

2,4-dichloro-5-thiazolylmethyl chloride,

4-imidazolylmethyl chloride,

1-methyl-2-imidazollymethyl chloride,

1,2.4-triazol-5-ylmethyl chloride,

1-Methyl-1,2,4-triazol-3-ylmethyl chloride

1,2.5-thiadiazol-4-ylmethyl chloride,

1,2.3-thiadiazol-5-ylmethyl chloride,

3-Methyl-1,2,4-oxadiazol-5-ylmethyl chloride

1,3-dioxolan-2-ylmethyl chloride,

2,2-dimethyl-1,3-dioxolan-4-ylmethyl chloride,

2-Methyl-2-oxazolin-5-ylmethyl chloride

2-Trifluoromethyl-2-oxazolin-5-ylmethyl chloride

3-pyrrolylmethyl chloride,

1-methyl-3-pyrrolylmethyl chloride,

5-Methyl-3-thienyl chloride

5-methyl-3-pyrrolylmethyl chloride,

1,5-dimethyl-3-pyrrolylmethyl chloride,

2,5-dimethyl-3-furylmethyl chloride,

2,5-dimethyl-3-thienylmethyl chloride,

5-fluoro-3-furyrylmethyl chloride,

4-chlorofurfuryl chloride,

5-chlorfurfuryl chloride,

5-chloro-3-furylmethyl chloride,

5-chloro-3-thienylmethyl chloride,

5-chloro-1-methyl-3-pyrrolylmethyl chloride,

5-bromo-3-furylmethyl chloride,

5-Trifluoromethylfurfuryl chloride,

5-trifluoromethyl-3-thienylmethyl chloride, 1-methyl-5-trifluoromethyl-3-pyrrolylmethyl chloride, 5-methylfurfuryl chloride,

3-Isoxazolylmethyl chloride

4-isoxazolylmethyl chloride,

3-fluoro-5-isoxazolylmethyl chloride,

3-bromo-5-isoxazolylmethyl chloride,

2,5-dimethyl-4-isoxazolylmethyl chloride,

3-isothiazolylmethyl chloride,

4-isothiazolomethyl chloride,

3-pyrazolylmethyl chloride,

1- (4-pyrazolyl) ethyl chloride

1-methyl-3-pyrazolylmethyl chloride,

1-methyl-5-pyrazolylmethyl chloride,

1-propyl-4-pyrazolylmethyl chloride,

3-chloro-1-methyl-5-pyrazolylmethyl chloride,

5-Trifluoromethyl-3-pyrazolylmethyl chloride

1-methyl-3-trifluoromethyl-3-pyrazolylmethyl chloride,

1-methyl-3-trifluoromethyl-5-pyrazolylmethyl chloride,

4-Oxazolylmethyl chloride

2-Methyl-4-oxazolylmethyl chloride

2-methyl-5-oxazolylmethyl chloride,

2-fluoro-5-oxazolylmethyl chloride,

2-chloro-5-oxazolylmethyl chloride,

2-trifluoromethyl-5-oxazolylmethyl chloride,

2,4-dimethyl-5-oxazolylmethyl chloride,

1- (5-thiazolyl) ethyl chloride,

2-methyl-4-thiazolylmethyl chloride,

1- (2-Methyl-5-thiazolyl) ethyl chloride

4-methyl-5-thiazolylmethyl chloride,

2-fluoro-4-thiazolylmethyl chloride,

2-fluoro-5-thiazolylmethyl chloride,

1- (2-chloro-5-thiazolyl) ethyl chloride,

2-Trifluoromethyl-5-thiazolylmethyl chloride

2-imidazolylmethyl chloride,

1-Methyl-5-imidazolylmethyl chloride

2-fluoro-4-imidazolylmethyl chloride,

2-chloro-4-imidazolylmethyl chloride, 1-methyl-2-trifluoromethyl-4-imidazolylmethyl chloride, 1-methyl-1,2,3-triazol-4-ylmethyl chloride,

1- (1-Methyl-1,2,3-triazol-4-yl) ethyl chloride

3-Methyl-1,2,4-triazol-5-ylmethyl chloride

3-Trifluoromethyl-1,2,4-triazol-5-ylmethyl chloride

1,2.4-Oxadiazol-5-ylmethyl chloride

1.3.4-Oxadiazol-2-ylmethyl chloride

T, 2,3-oxadiazol-5-ylmethyl chloride,

3-Trifluoromethyl-1,2,4-oxadiazol-5-ylmethyl chloride

2-Methyl-1,3,4-oxadiazol-5-ylmethyl chloride

2-Trifluoromethyl-1,3,4-oxadiazol-5-ylmethyl chloride

1,2.4-thiadiazol-5-ylmethyl chloride,

1,2.3-thiadiazol-4-ylmethyl chloride,

1- (1,2,3-thiadiazol-5-yl) ethyl chloride,

1.3.4-thiadiazol-2-ylmethyl chloride,

1- (1,3,4-Thiadiazol-2-yl) ethyl chloride

1,2.5-thiadiazol-3-ylmethyl chloride,

3-Methyl-1,2,4-thiadiazol-5-ylmethyl chloride

4-Methyl-1,2,3-thiadiazol-5-ylmethyl chloride

2-methyl-1,3,4-thiadiazol-5-ylmethyl chloride, 2-trifluoromethyl-1,3,4-thiadiazol-5-ylmethyl chloride,

2-fluoro-1,3,4-thiadiazol-5-ylmethyl chloride,

2-chloro-1,3,4-thiadiazol-5-ylmethyl chloride,

3-chloro-1,2,5-thiadiazol-4-ylmethyl chloride, 1- (3-tetrahydrofuryl) ethyl chloride,

3-tetrahydrothienylmethyl chloride,

1- (3-tetrahydrothienyl) ethyl chloride

1-Methyl-3-pyrrolydinylmethyl chloride

1,3-oxathiolan-2-ylmethyl chloride,

1,3-dioxolan-4-ylmethyl chloride,

1,3-oxathiolan-4-ylmethyl chloride,

1,3-dithiolan-4-ylmethyl chloride, thiazolidin-5-ylmethyl chloride,

4-Methyl-1,3-dioxolan-2-ylmethyl chloride

2-Methyl-1,3-oxathiolan-4-ylmethyl chloride

2-Trifluoromethyl-1,3-dioxolan-4-ylmethyl chloride

3-Thiolen-5-ylmethyl chloride

2- isoxazolin-5-ylmethyl chloride,

3-methyl-2-isoxazol-5-ylmethyl chloride, 3-trifluoromethyl-2-isoxazolin-5-ylmethyl chloride,

2,4-dimethyl-2-oxazolin-4-ylmethyl chloride, 2-methyl-1,3-thiazolin-4-ylmethyl chloride,

2-Oxazoilidon-5-ylmethyl chloride

3-Methyl-2-thiazolidinon-5-ylmethyl chloride,

3-methyl-2-thioxothiazolidin-5-ylmethyl chloride, 3-chloro-1,2,4-oxadiazol-5-ylmethyl chloride,

4-pyrimidinylmethyl chloride,

2-methyl-4-pyrimidinylmethyl chloride,

5-pyrimidinylmethyl chloride,.

2-methyl-5-pyrimidinylmethyl chloride,

2,4,6-trichloro-5-pyrimidinylmethyl chloride, pyrazinylmethyl chloride,

1- (pyrazinyl) ethyl chloride

2-methyl-5-pyrazinylmethyl chloride,.

3-pyridazinylmethyl chloride,

2-chloro-4-pyrimidinylmethyl chloride,

4-chloro-6-pyrimidinylmethyl chloride,

4-methyl-6-pyrimidinylmethyl chloride,

2-fluoro-5-pyrimidinylmethyl chloride,

1- (2-fluoro-5-pyrimidinyl) ethyl chloride,

2-chloro-5-pyrimidinylmethyl chloride,

2-trifluoromethyl-5-pyrimidinylmethyl chloride,

2-chloro-5-pyrazinylmethyl chloride,

2-Trifluoromethyl-5-pyrazinylmethyl chloride

3-fluoro-6-pyridazinylmethyl chloride,

3-Methyl-6-pyridazinylmethyl chloride

4-pyridazinylmethyl chloride,

3-chloro-6-pyridazinylmethyl chloride,

4-pyridazinylmethyl chloride,

3-Trifluoromethyl-6-pyridazinylmethyl chloride

1.3.5-triazin-2-ylmethyl chloride,

3-chloro-1,2,4-triazin-6-ylmethyl chloride,

3,5-dichloro-1,2,4-triazin-6-ylmethyl chloride; and 3-chloro-1,2,4,5-tetrazin-6-ylmethyl chloride.

Instead of the above chlorides, the corresponding bromides or p-toluenesulfonates can also be exemplified. These compounds will be described in more detail below.

The above halogens, for example chlorides, can easily be prepared by chlorination of the corresponding alcohols with thlonyl chloride.

For example, 2-chloro-5-pyridylmethyl chloride can be obtained by chlorination of 2-chloro-5-pyridylmethylalcohol with thionyl chloride (cf. J. Org. Chem., Vol. 34, 3547).

Bromides can also be prepared by bromination of a methyl group in the side chain with N-bromosuccinimide. ·

Some trifluoromethyl-substituted pyridyl alcohols are described in J. Med. Chem., Vol. Using these synthesis methods, 2-methyl-5-trifluoromethylpyridine, obtained by reacting 6-methyl-nicotinic acid with hydrofluoric acid and sulfur hexafluoride, is converted to the N-oxide and the N- rearrangement. The 5-trifluoromethyl-2-pyridylmethyl alcohol can be obtained.

This reaction can also be used to synthesize 5-methyl-2-trifluoromethylpyridine from 5-methyl-picolinic acid. The 2-trifluoromethyl-5-pyridylmethyl bromide (or chloride) required as starting material can be prepared by monohalogenating the above 5-methyl-2-trifluoromethylpyridine with N-bromosuccinimide or N-chlorosuccinimide.

The reaction of thiourea instead of thioacylamide can lead to 2-amino-4-chloromethyl- or 2-amino-5-chloromethylthiazole, and through the diazotization further halogen atom can be introduced etc. This halogen is active and can be converted to 2-alkoxy by sodium alkoxide (cf. Japanese Published Patent Application No. 5972/1979 and J. Chem. Soc., Perkin I, 1982, pp. 159-164).

2-Halo-4- or -5-bromomethylthiazole can be prepared by bromination of 2-halo-4- or 5-methylthiazoles with N-bromosuccinimide.

Use of ammonium dithiocarbamate (Org. Synthesis, Coll. Vol. 0 III, p. 763) in place of tb.acetamide in the above reaction may result in 4- or 5-halomethyl-2-me; 1.úptothiazoles. Alkylation or haloalkylation may then afford 2-alkylthio-4- or

5-halo-methylthiazoles, or 2-substituted alkylthio-4- or 5-halomethylthiazoles (JACS, Vol. 75, pp. 102-103).

Halomethylimidazoles, for example chloromethylimidazole, can be obtained by hydroxymethylation of N-alkylimidazole with formaldehyde, optionally by dealkylation of this compound to give hydroxymethylimidazole, and chlorination of this compound with thionyl chloride, etc. in a conventional manner (cf. J.

ACS, Vol. 71, pp. 383-386). The 4-hydroxymethylimidazole exemplified by hydroxymethylimidazole is readily prepared from fructose formaldehyde and ammonia (cf. Org. Synthesis Coll., Vol. III, p. 460).

Hydroxymethyltriazole can be prepared, for example, as described in JACS, Vol. 77, pp. 1,538-1,540, and chlorination of this compound yields chloromethyl triazole.

Halomethyl-oxadiazoles and halomethylthiazoles can be prepared by bromination of methyl-substituted oxazole and methyl-substituted thiazole with N-bromosuccinimide. 3-Bromomethyl-1,2,5-thiadiazole is disclosed in Japanese Published Application No. 24,963 / 1974 and 3-bromomethyl-4-chloro-1,2,5-thiadiazole is exemplified. Halomethyloxadiazoles and halomethylthiadiazoles can be prepared by direct cyclization. For example, 5-chloro-3-chloromethyl-1,2,4-thiadiazole is described in J. Org. Chem., Vol. 27, p. 2 589-2 592, 3-chloro-5-chloromethyl-1,2,4-oxadiazole is disclosed in German Offenlegungsschrift 2,054,342, and

5-Chloromethyl-3-methyl-1,2,4-oxadiazole is described in Bull. Soc. Chim. Belges., Vol. 73, pp. 793-798 as typical examples of these compounds. 5-chloromethyl-1,3,4-oxa (or thia) diazole which is substituted in the 2-position is described in French Patent No. 1,373,290 as another typical example. .

Chloromethyl-substituted heterocyclic compounds can be prepared by reducing the carboxylic acids or ester derivatives of these acids with lithium aluminum hydride, etc., converting said compounds to alcohol derivatives, and chlorinating the alcohol derivatives with thionyl chloride, etc. Examples of such compounds are disclosed in Japanese Patent Application No. 89633/1984. - chloromethyl-1,2,3-thiadiazole, 4-chloromethyl-1-methyl-1,2,3,5-tetrazole and 4-chloromethyl-1-methyl-1,2,3-triazole.

Haloalkyl-substituted, saturated or partially unsaturated heterocyclic compounds can be converted to chloromethyl-substituted compounds, for example by chlorination of their corresponding alcohol derivatives in a conventional manner.

Bromomethyldioxolane and bromomethyloxothiolane can be prepared by reacting dimethyl bromoacetal with ethylene glycol or by reacting dimethyl bromoacetal with 2-mercaptoethanol or by reacting an aldehyde or ketone with epibromohydride. For example, 2-bromomethyl-1,3-dioxolane is described in Beilstein, Vol. 19, II, p. 8.

For chloromethyl-substituted oxazoline derivatives, for example, 5-chloromethyl-3-methyl-2-isoxazoline can be prepared according to the data in Pak. J. Sci. pers., Vol.

30, pp. 91-94. 5-Chloromethyl-3-trifluoromethyl-2-isoxazoline can be prepared by chlorination

3-Trifluoromethyl-5-hydroxymethyl-2-isoxazoline_/ which is described in Bull. Chem. Soc. Japan, Vol. 57, pp. 2 184-2 187 in the usual manner. 5-chloromethyl-2-methyloxazoline is described in Tetrahedron, Vol. 34, pp. 3,537-3,544.

4-Chloromethyl-2-methyl-2-thiazoline can be prepared by chlorination of 4-hydroxymethyl-2-methyl-2-thiazoline described in Hetercycles, Vol. 4, pp. 1 687-1 692. 5-Chloromethyl-3-methyloxazo-255867 lidin-2-one is a compound disclosed in German Patent Publication No. 1,933,219. 3-Bromomethyl-1,1-dioxo-3-thiolene is a compound No. 4,561,764 and can be prepared by bromination with N-bromosuccinimide.

5-pyrimidinylmethyl alcohol is obtained from 5-pyrimidinecarbaldehyde and 2-chloro-5-pyrimidinylmethyl alcohol is obtained from 2-chloro-5-pyrimidinecarbaldehyde.

3-Pyridazinylmethyl alcohol was prepared from furfurylacetate (Acta Chem. Scand., Vol. 1, p. 619). Pyrazinylalkyl halides, methylpyrazines or dimethylpyrazines can be used to convert to chloromethylpyrazine using N-chlorosuccinimide (Synthesis, 1984, pp. 676-679). This reaction is applicable to methylpyrazines having other substituents and halo-substituted methylpyridazines such as 3-chloro-6-methylpyridazine (described in J. Chem. Soc., 1947, p. 6). 242), and 3-chloro-6-pyridazinylmethyl chloride can be prepared by this reaction. 2-Chloro-5-pyrimidinylmethyl bromide can be obtained from 2-chloro-5-methylpyrimidine (cf. Reacts. Identity. Org. Soedin., Vol. 5, pp. 824-837) and N-bromosuccinimide.

Ethyl 2-chloropyrazine-5-carboxylate can be prepared as described in J. Heterocycl. Chem., Vol. 19, p. 407 and Chem. Pharm. Bull · Vol. 28, pp. 3,057 and 3,063. The compound obtained can then be reduced to the corresponding methanol derivative.

For triazinylalkyl halides, for example, 2,5-triazin-2-ylmethyl chloride can be obtained by reacting 2-methyl-1,3,5-triazine with N-chlorosuccinimide (J. Org. Chem., Vol. 29, p. 1) 527 to 1537). 3,5-dichloro-6-methyl-1,2,4-triazine (described in J. Med. Chem., Vol. 10, pages 883-887) and 3-chloro-6-methyl-1,2, 4,5-Tetrazine (J. Org. Chem., Vol. 46, pp. 5,102 to 5,109) can be chlorinated in a similar manner by reaction with N-chlorosuccinimide.

i '

In the compounds of formula I wherein X is -NH or Y is -CH and obtainable by processes a), b), c), d), e) or f) as described above, each hydrogen atom may be the -NH groups and = CH groups of these compounds to substitute or add to other groups.

By way of example, some compounds containing an active olefinic bond, such as methyl vinyl ketone, ethyl acrylate and acrylonitrile, can be added to the hydrogen atom of the group = CH-Michaol reaction (cf. Japanese Patent Application Publication No. 151 882/1975).

In addition, a dialkylaminomethyl group can be introduced onto the carbon atom at the alpha position of the nitromethylene group by the Mannich reaction and the like, and active aldehydes such as formaldehyde and chloral can also be well added (cf. Japanese Patent Application Publication No. 151 882/1975).

Further, each hydrogen atom of the above-mentioned -NH and = CH groups can also be halogenated by a halogenating agent such as N-chlorosuccinimide, N-bromosuccinimide, perchlorofluoride and halogen itself (cf. U.S. Patent Nos. 3,933,809 and 3,962,233). Japanese Patent Application Publication No. 54532/1974).

In the above cases, the compounds of formula I correspond to the following formula

<img file="CS255867B2_D0035.tif" />

L - C - NO₂

Hal in which

3 4 n, R, R, R, R, R, Z, and Hal have the above meanings and

L is halogen, phenylthio or alkoxycarbonyl.

Glyoxylic acid and dimethylformaldehyde dimethylacetal may also react with a carbon atom in the alpha position of the nitromethylene group, the compounds of formula I corresponding to the following formula

<img file="CS255867B2_D0036.tif" />

HOOC-HC

<img file="CS255867B2_D0037.tif" />

wherein n, R, R, R, R, R a and R 2 are as defined above.

The nitrogen atom of the aforementioned -NH group and the carbon atom in the alpha position of the nitromethylene group can independently be acylated, sulfenylated or sulfonylated (cf. Dutch Patent Publication No. 7,306,145, U.S. Patent Nos. 3,985,736, 3,996,372, 4,020,061, 4,022,775, 4,052,411, 4,053,662 and 4,076,813).

Acyl isocyanates and sulfonyl isocyanates can also react with a carbon atom in the alpha position of the nitromethylene group (cf. U.S. Patent Nos. 4,013,766, 4,025,634, 4,029,791 and 4,034,091).

The nitrogen atom of the above nitro group can also be alkylated (cf. Belgian Patent No. 821,282) and the reaction can be alkylated at the 3-position of imidazolidines or tetrahydropyrimidines to give the corresponding compounds of formula I.

In carrying out process (a), all inert organic solvents may be suitable as diluents.

Examples of such diluents include water, aliphatic, alicyclic or aromatic hydrocarbons (which are optionally chlorinated) such as hexane, cyclohexyne, petroleum ether, ligroin, benzene, toluene, xylene, methylene chloride, chloroform, carbon tetrachloride, ethylene chloride, trichlorethylene and chlorobenzene; ethers such as diethyl ether, methylethyl ether, diisopropyl ether, dibutyl ether, propylene oxide, dioxane and tetrahydrofuran, nitriles such as acetonitrile, propionitrile and acrylonitrile, alcohols, such as methanol, ethanol, isopropyl alcohol, butanol and ethylene glycol, acid amides such as dimethylformamide and dimethylacetamide, sulfones and sulfoxides such as dimethylsulfoxide and sulfolane, as well as bases such as pyridine.

Process a) can be carried out over a wide temperature range. Generally, the process is carried out at temperatures between about -20 ° C and the boiling point of the reaction mixture, especially at temperatures between about 50 ° C and about 120 ° C. The reaction is usually carried out at atmospheric pressure, but if necessary, it can be carried out at elevated or reduced pressure.

In process (a), the desired novel compounds of the formula I can be obtained, for example, by reacting compounds of the formula II with one to about 1.2 mol, in particular 1 to about 1.1 mol, to 1 mol of the compounds of formula II in an inert solvent such as an alcohol, for example methanol or ethanol until the evolution of mercaptan ceases.

In carrying out processes (b) and (c), suitable diluents may be the abovementioned solvents exemplified for process (a). As the base, for example, alkali metal hydroxides, carbonates, bicarbonates and alkoxides, as well as tertiary amines such as triethylamine, diethylamine and pyridine can be used.

Processes b) and c) can be carried out over a wide range of temperatures, generally at temperatures between about -20 ° C and the boiling point of the reaction mixture, especially at temperatures between about 0 ° C and about 50 ° C.

The reaction is preferably carried out at atmospheric pressure, but can also be carried out at elevated or reduced pressure.

In the above processes b) and c), for example, about 1 to about 5 moles, preferably about 2 to about 4 moles of base and about 0.9 to about 4 moles, especially about 1 to about 3 moles of a compound of formula V or IV can be used. per mole of the compound of formula II.

In carrying out process (d), suitable diluents may be the aforementioned inert solvents exemplified for process (a).

According to process d), the desired compounds of the formula I can be easily obtained, for example, by reacting 1 mol of the compound of the formula II with 1 to about 1.2 mol, in particular 1 to about 1.1 mol, of nitroguanidine with heating in an aqueous solvent.

Process d) can be carried out at a temperature of, for example, about 0 ° C to about 100 ° C, in particular at about 30 ° C to about 80 ° C. This reaction is preferably carried out at atmospheric pressure, but can also be carried out at elevated or reduced pressure.

In the practice of process e), the compounds of the general formula VI are usually dissolved in an acid, such as sulfuric acid, before the actual reaction begins.

In the process, the compounds of formula VI and fuming nitric acid (at least 98% pure) are reacted at low temperatures, in particular at about 0 ° C or below, to give the desired compounds of formula I (using the method described in UK application). No. 2,055,796).

The compounds of formula (VI) are used in the above-described process generally in the form of the hydrohalide as formed in the above-described synthesis, and are generally neutralized in a conventional manner prior to use in process (e).

In the practice of the process of the invention (process f)), suitable diluents may be inert organic solvents exemplified above for process a). As bases, for example, hydrides such as sodium hydride and potassium hydride, alkali metal hydroxides and carbonates can be used.

Process f) can be carried out over a wide range of temperatures, generally at temperatures between about 0 ° C and about 100 ° C, preferably between about 10 ° C and about 80 ° C.

The reaction according to process f) is carried out, in particular, at atmospheric pressure but can also be carried out at elevated or reduced pressure.

In process f), the desired compounds of the formula I can be obtained, for example, by reacting compounds of the formula VII in the presence of about 1.1 to 1.2 moles per 1 mol of the compound of formula VII, sodium hydride as a base, in 1 to about 1.2 moles. in particular 1 to about 1.1 mol, per 1 mol of the compound of formula VII, the compound of formula VIII in an inert solvent such as dimethylformamide. In process f) it is preferred to convert the compound of formula VII to its sodium salt using sodium hydride prior to the reaction itself. Due to the properties of sodium hydride, it is desirable to carry out this reaction under a nitrogen gas atmosphere.

The compounds of formula (I) produced by the process of the present invention also include tautomeric compounds as shown in the following scheme.

Where X is NH and Y is CH, this can be represented by the following formulas:

<img file="CS255867B2_D0038.tif" />

chno₂

<img file="CS255867B2_D0039.tif" />

O

OH

Where X is NH and Y is N, this can be represented by the following formulas:

<img file="CS255867B2_D0040.tif" />

<img file="CS255867B2_D0041.tif" />

NH-NO3

Q

When Y is CR, the compounds of formula I may additionally include the E, Z-isomer.

The compounds of formula I may also be present in the form of a salt. Examples of such salts include salts with inorganic acids, salts with organic acids and salts with metals.

The active compounds according to the invention have significant insecticidal effects.

Said compounds can be used as insecticides. The active ingredients can be used to combat a wide range of pests, including absorbent insects, biting insects and other plant pests, cereal stock pests and sanitary pests.

Examples of such pests are:

from the order of beetles (Coleoptera)

Callosobruchus chinensis, Weevil (Sitophilus zeamais), Darkworm (Tribolium castaneus), Epllachna vigostomaculata, Agriotes fuscicollis, Foliage (Anomala rufocuprea), Colorado potato beetle (Leptinotarsa ​​decemlineata), Diabrotica spec.

Lissorhoptrus oryzophilus and boar (Lyctus brunneus);

from the order of the Lepidoptera, Lymantria dispar, Malacosoma neustria, Pieris rapae,

Spodoptera litura, Cabbage moth (Mamestra brassicae),

Chilo suppressalis,

Pyrausta nubilalis, Ephestia cautella,

Adoxophyes orana,

Carpocapsa pomonella, Agrostis fucosa, Galleria mellonella, Plutella maculipennis and Phyllocnistis citrella;

of the order Homoptera

Nephotettix cincticeps,

Nilaparvata lugens,

Pseudococcus cometocki,

Unaspis yanonensis, Peach Aphid (Myzus persicae), Aphis pomi,

Aphis gossypii, Aphid (Rhopalosiphum pseudobrassicae),

Stephanitis nashi,

Nazara spec.,

Cimex lectularius, Greenfin whitefly (Trialeurodes vaporariorum) and Mera (sylla spec.);

from the order of the Orthoptera, the cockroach (Blatella germanica), the cockroach (Periplaneta americana), the mole cricket (Gryllotalpa africana) and the locust; and migratoria migratoriodes;

⁴¹ Isoptera

Deucotermes speratus a

Coptotermes formosanus;

from the order of the diptera (House flies) (Musea domestica), mosquito (Aedes aegypti), flower (Hylemyia platura), mosquito (Culex pipiens), anofeles (Anopheles sinensis) and mosquito (Culex tritaeniorhynchus).

In the field of veterinary medicine, the novel compounds of the formula I according to the invention are active against various harmful parasites of animals (endo- and ectoparasites), such as against insects and nematodes. Examples of such parasides are given below:

Insect:

(Hamstrell spec.), Stomoxys spec., Trichodectes spec.

Rhodnium spec, and dog flea (Ctenocephalides canis).

Substances having pesticidal activity against these pest species are sometimes referred to simply as insecticides in the specification.

The active compounds may be converted into the customary formulations, such as solutions, emulsions, suspensions, powders, foams, pastes, granulates, aerosols, natural and synthetic substances impregnated with the active compounds, encapsulated in polymeric substances and seed coatings, flammable additives such as smoke cartridges, smoke jars, smoke spirals and the like, as well as ULV formulations applied in the form of cold and warm fog. . . .

. These compositions are prepared in a manner known per se, for example by mixing the active compounds with fillers, i.e. liquid solvents, with gases which are under pressure in the liquefied state and / or with solid carriers, optionally with surfactants, i.e. emulsifiers and / or and dispersants and / or foaming agents. If water is used as a filler, for example, organic solvents can also be used as co-solvents.

Basically suitable liquid solvents are: aromatic hydrocarbons, such as xylene, toluene, or alkynaphthalenes, chlorinated aromatics or chlorinated aliphatic hydrocarbons, such as chlorobenzenes, chlorohydrenes or methylene chloride, aliphatic hydrocarbons, such as cyclohexane or paraffinic hydrocarbons. for example, petroleum fractions, alcohols such as butanol or glycol, and esters and ethers thereof, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, strongly polar solvents such as dimethylformamide and dimethylsulfoxide, and water.

Liquefied gaseous carriers or fillers are liquids which are gaseous substances at ordinary temperature and at atmospheric pressure, such as aerosol propellants such as halogenated hydrocarbons, as well as butane, propane, nitrogen and carbon dioxide.

Suitable solid carriers are, for example, natural stone meal, such as kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite or diatomite, and synthetic stone meal, such as highly dispersed silicic acid, alumina and silicates; suitable solid carriers for the granules are, for example, crushed and fractionated natural minerals, such as limestone, marble, pumice, sepiolite, dolomite, as well as synthetic granules of inorganic and organic flours, as well as granules of organic material such as sawdust, shells coconuts, corn cobs and tobacco stems.

Suitable emulsifiers and / or foaming agents are, for example: nonionic and anionic emulsifiers, such as polyoxyethylene fatty acid esters, fatty alcohol polyoxyethylene ethers, for example alkylaryl polyglycol ethers, alkylsulfonates, alkylsulfates, arylsulfonates as well as protein hydrolysates; suitable dispersants are, for example, lignin from sulphite waste liquors and methylcellulose.

Adhesives such as carboxymethylcellulose, natural and synthetic powdered, granular or latex polymers such as acacia, polyvinyl alcohol, polyvinyl acetate may also be used in these compositions.

Additionally, dyes such as inorganic pigments such as iron oxide, ferrocyanide blue, titanium dioxide and organic dyes such as alizarin dyes, azo dyes, metal phthalocyanine dyes and trace elements such as iron, manganese, boron, copper, cobalt salts can be added to said compositions , molybdenum and zinc.

The compositions generally contain between 0.1 and 95% by weight of active ingredient, preferably between 0.5 and 90% by weight of active ingredient.

The active compounds according to the invention may be present in the corresponding commercial preparations and in the application formulations prepared therefrom in the form of a mixture with other active compounds, such as insecticides, baits, sterilizing agents, acaricides, nematicides, fungicides, growth regulators or herbicides. As insecticides, for example, phosphates, carbamates, carboxylates, chlorinated hydrocarbons, phenylureas, substances produced by microorganisms can be used.

Further, the active compounds of the present invention may be present in the formulations of the present invention in the formulations to be marketed and in the formulations prepared from these formulations as a mixture with synergistically active substances. The synergistic active ingredient is a compound that enhances the effect of the active compounds without having to be active as such.

The concentration of the active ingredient in the application formulations which are prepared from formulations intended for the market may vary within wide limits. Thus, the concentration of active compound in the dosage forms can be from 0.000.000 l to 100% by weight, in particular 0.000 * 1 to 1% by weight.

The compounds of the invention are used in conventional manner in accordance with the respective dosage forms.

When used against hygiene pests and against storage pests, the active compounds according to the invention are distinguished by an excellent residual effect on wood and clay and good stability to alkalis on lime substrates.

The following examples illustrate the invention in more detail. However, these examples do not limit the scope of the invention in any way.

Examples illustrating a process for the preparation of active substances

<img file="CS255867B2_D0042.tif" />

Examples illustrating a process for the preparation of active substances

Example 1 (Compound No. 1)

A mixture of 4.3 g of N- (2-chloro-5-pyridylmethyl) -3-aminopropanethiol, 3.3 g of 1-nitro-2,2-bis (methylthio) ethylene and 40 ml of ethanol is heated to reflux for 30 minutes. for 10 hours in a stream of nitrogen. After the reaction, about 2/3 of ethanol was distilled off under reduced pressure. Then ether is slowly added to the reaction mixture to precipitate crystals. The crystals were filtered off and washed with a mixture of ethanol and ether. 1.3 g of 3- (2-chloro-5-pyridylmethyl) -2-nitromethylenetetrahydro-2H-1,3-thiazine, m.p. 164 DEG-166 DEG C., are obtained in the form of yellow crystals.

Example 2

<img file="CS255867B2_D0043.tif" />

(Compound # 2)

2.9 g of 2-nitromethylenthiazolidine are dissolved in 30 ml of absolute acetonitrile and 0.9 g of 60% sodium hydride are added at room temperature under a nitrogen atmosphere. The reaction mixture was then stirred at room temperature until evolution of hydrogen ceased. A solution of 3.2 g of 2-chloro-5-pyridylmethyl chloride in 5 ml of absolute acetonitrile was then added at room temperature and the reaction mixture was stirred at room temperature for 1 day. The acetonitrile is then distilled off under reduced pressure and dichloromethane is added to the residue. The mixture was then washed with water. The dichloromethane was distilled off from the dichloromethane layer. The residual oil was purified by silica gel column chromatography to obtain 1.6 g of the desired 3- (2-chloro-5-pyridylmethyl) -2-nitromethylenthiazolidine. Melting point: 177-179 ° C. .

Example3

C \ = chno₂

N

<img file="CS255867B2_D0044.tif" />

(Compound # 3)

A mixture of 1.8 g of N- (3-pyridylmethyl) -3-aminopropanethiol, 1.7 g of 1-nitro-2,2-bis (methylthio) ethylene and 40 ml of ethanol is heated under reflux for 5 hours under nitrogen atmosphere. After completion of the reaction, about 2/3 of the volume of ethanol is distilled off under reduced pressure. Then ether is added slowly to the reaction mixture to precipitate crystals. The crystals were filtered off and washed with a mixture of ethanol and ether. 1.2 g of the desired 3- (3-pyridylmethyl) -2-nitromethylenetetrahydro-2H-1,3-thiazine are obtained. M.p. 143-146 ° C.

<img file="CS255867B2_D0045.tif" />

Example 4 (Compound No. 4)

2.9 g of 2-nitromethylenthiazolidine are suspended in 30 ml of absolute acetonitrile and 0.9 g of 60% sodium hydride are added under a stream of nitrogen. The reaction mixture was then stirred at room temperature until evolution of hydrogen ceased. Then 3.2 g of 3-picolyl chloride dissolved in 5 ml of absolute acetonitrile are added. The reaction mixture was stirred for 3 hours at room temperature. The acetonitrile is then distilled off under reduced pressure. Dichloromethane was added to the residue and the mixture was washed with water. The dichloromethane was distilled off from the dichloromethane phase and the residual oily product was purified by column chromatography to give 0.5 g of the desired 3- (3-pyridylmethyl) -2-nitromethylethylenthiazolidine. Melting point 96-100 ° C.

Example 5

H

СУ = СН1МО₂

N

<img file="CS255867B2_D0046.tif" />

(Compound No. 5)

A mixture of 16.8 g of N- (1-methyl-4-pyrazolylmethyl) trimethylenediamine, 16.5 g of 1-nitro-2,2-bis (methylthio) ethylene and 200 ml of ethanol is heated to reflux until evolution is complete. methylmercaptan. The reaction mixture was then cooled and the precipitated crystals were filtered off. Washing with methanol gave 16.6 of the desired 1- (1-methyl-4-pyrazolylmethyl) -2-nitromethylenetetrahydropyrimidine as pale yellow crystals. Melting point 186-190 ° C.

Example 6 (Compound No. 6)

<img file="CS255867B2_D0047.tif" />

A mixture of 15.5 g of N- (3-methyl-5-isoxazolylmethyl) ethylenediamine, 16.5 g of 1-nitro-2,2-bis (methylthio) ethylene and 200 ml of ethanol is heated to reflux until evolution ceases. methylmercaptan. This time is around 3 hours. The reaction mixture is then cooled to room temperature, whereby the desired product precipitates as crystals. The crystals were filtered off and washed with ethanol. 12.5 g of 1- (3-methyl-5-isoxazolylmethyl) -2-nitromethylenimidazolidine are obtained in the form of yellow crystals. Melting point 168-170 ° C.

Example 7

H

<img file="CS255867B2_D0048.tif" />

chno₂

<img file="CS255867B2_D0049.tif" />

(Compound No. 7)

12.9 g of 2-nitromethylenimidazolidine are dissolved in 60 ml of absolute dimethylformamide and 4.4 g of 60% sodium hydride are added slowly under a stream of nitrogen at room temperature and the reaction mixture is stirred at room temperature with gentle heating up to 30 ° C. for 3 hours to give the sodium salt of imidazolidine derivatives. The reaction mixture was then added

11.8 g of 5-isoxazolylmethyl chloride at room temperature and the mixture is stirred for 24 hours. The reaction mixture was then carefully poured into 10 ml of ice water and extracted twice with dichloromethane. The dichloromethane was distilled off from the dichloromethane layer to give 12 g of the desired 1- (5-isoxazolylmethyl) -2- (nitromethylene) imidazolidine as brown crystals. M.p. 156-158 ° C.

Example 8

<img file="CS255867B2_D0050.tif" />

(Compound No. 8)

18.5 g of N- (2-methyl-5-thiazolylmethyl) trimethylenediamine are dissolved in 100 ml of acetonitrile and 16.5 g of 1-nitro-2,2-bis (methylthio) ethylene are added. The reaction mixture was then heated to reflux with stirring for 6 hours. After the reaction was completed, the reaction mixture was cooled to room temperature. The precipitated crystals were filtered off and washed with methanol. 10.2 g of the desired 1- (2-methyl-5-thiazolylmethyl) -2- (nitromethylene) tetrahydropyrimidine are obtained. Mp 204-207 ° C.

Example 9

<img file="CS255867B2_D0051.tif" />

n-no₂

<img file="CS255867B2_D0052.tif" />

(Compound No. 9)

A mixture of 9.5 g of 2-fluoro-5-pyridylmethyl bromide, 6.5 g of 2- (nitroimino) imidazolidine, 7.6 g of potassium carbonate and 100 ml of acetonitrile is stirred and heated to reflux for 2 hours. After the reaction was completed, the reaction mixture was cooled to room temperature and 100 mL of cold water was added. The precipitated crystals are filtered off and washed with ether. 6.0 g of light colored 1- (2-fluoro-5-pyridylmethyl) -2- (nitroimino) imidazolidine are obtained. Melting point 121-124 ° C.

Example 10

<img file="CS255867B2_D0053.tif" />

(Compound No. 10)

A solution of 10 g of N- (2-chloro-5-pyridylmethyl) trimethylenediamine, 5.7 g of nitroguanidine in 80 ml of water is heated at 80 ° C for 3 hours. The reaction mixture was cooled to room temperature and then extracted twice with 50 ml of dichloromethane. Dichloromethane is distilled off from the organic phase and the tar residue is purified by silica gel chromatography to give

6.1 g of nearly colorless 1- (2-chloro-5-pyridylmethyl) -2- (nitroimino) tetrahydropyrimidine. Melting point 113-117 ° C.

Example 11-i

<img file="CS255867B2_D0054.tif" />

A solution of 18.6 g of N- (2-chloro-5-pyridylmethyl) ethylenediamine in 200 ml of toluene is stirred at room temperature and then 10.6 g of cyanogen bromide are added portionwise. The reaction mixture is then further stirred. If the desired 1- (2-chloro-5-pyridylmethyl) -2-iminoimidazolidine precipitates as the hydrobromide, the reaction mixture is filtered and the residue on the filter is washed with ether. Melting point 202-205 ° C.

Example 11-ii

<img file="CS255867B2_D0055.tif" />

(Compound No. 11)

5.8 g of hydrobromide prepared as described in Example 11-i were added to 98% sulfuric acid (30 ml) at 0 ° C. Then 2 ml of fuming nitric acid are added dropwise to the mixture at 0 ° C with stirring. After the addition, the reaction mixture was stirred at 0 ° C for 2 hours. The reaction mixture was then poured into 100 g of ice water and extracted with dichloromethane. The dichloromethane was distilled off from the dichloromethane phase under reduced pressure to give pale yellow crystals. The crystals were washed with ether to give 1.5 g of 1- (2-chloro-5-pyridylmethyl) -2- (nitroimino) imidazolidine. M.p. 136-139 ° C.

Example 11-iii

<img file="CS255867B2_D0056.tif" />

(Compound 12)

0.48 g of sodium hydride was added to a solution of 2.4 g of 2,2,2-trifluoroethanol in 30 ml of toluene and the reaction mixture was stirred until the evolution of hydrogen ceased. Thus, the sodium salt of 2,2,2-trifluoroethanol is prepared. 5.1 g of 1- (2-chloro-5-pyridylmethyl) -2- (nitroimino) imidazolidine, prepared as described in Example 3, and a catalytic amount were added to the obtained product.

4-dimethylaminopyridine. The reaction mixture was heated to 80 ° C for 10 hours with stirring. After cooling the reaction mixture, the precipitated crystals were filtered off, washed with water and ether and then purified by silica gel chromatography. 1.5 g of 1- [2- (2,2,2-trifluoroethoxy) -5-pyridylmethyl] -2- (nitroimino) imidazolidine are obtained. M.p. 109-112 ° C.

<img file="CS255867B2_D0057.tif" />

Example 12 (Compound No. 13)

A mixture of 15.2 g of N- (5-pyrimidinylmethyl) ethylenediamine, 14.9 g of 1-nitro-2,2-bis (methylthio) ethylene and 100 g of ethanol is heated to reflux with stirring until the evolution of methylmercaptan is complete ( i.e. for about 3 hours). The reaction mixture was cooled to room temperature and the precipitated crystals were filtered off. The crystals were then washed with ethanol and dried. 12.7 g of 1- (5-pyrimidinylroethyl) -2- (nitromethylene) imidazolidine are obtained in the form of pale yellow crystals. These crystals decompose at 236 ° C.

Example 13

<img file="CS255867B2_D0058.tif" />

CHMO₂

<img file="CS255867B2_D0059.tif" />

(Compound No. 14)

12.9 g of 2-nitromethylenimidazolidine are dissolved in 100 ml of absolute dimethylformamide and then 4.4 g of 60% oily sodium hydride are added at room temperature. The reaction mixture was stirred at room temperature until evolution of hydrogen ceased. 14.3 g of 2-methyl-5-pyrazinylmethyl chloride are then added at room temperature and the mixture is stirred for 8 hours at 40 ° C. After cooling to room temperature, 200 ml of water are added to the reaction mixture and extraction is performed with dichloromethane. Distillation of the dichloromethane from the organic phase under reduced pressure gave 5.4 g of 1- (2-methyl-5-pyrazinylmethyl) -2- (nitromethylene) imidazolidine as yellow crystals, m.p. 163-166 ° C.

Example 14

<img file="CS255867B2_D0060.tif" />

(Compound No. 15)

A mixture of 2 g of 2-amino-1- (2-chloro-5-pyridylmethylamino) propane, 1.6 g of 1-nitro-2,2-bis (methylthio) ethylene and 1 ml of methanol is heated for 5 hours at room temperature. stirring to reflux. Upon standing at room temperature, a crystalline product precipitates. The product was filtered off, washed with methanol and dried in vacuo. 1.9 g of 1- (2-chloro-5-pyridylmethyl) -4-methyl-2- (nitromethylene) imidazolidine are obtained in the form of pale yellow crystals. Melting point 170-174 ° C.

Example 15

<img file="CS255867B2_D0061.tif" />

ch-no₂ (Compound No. 16)

A mixture of 2.6 g of N- (3-methyl-5-isoxazolylmethyl) -1 '- (1-methyl-4-pyrazolylmethyl) trimethylenediamine, 1.6 g of 1-nitro-2,2-bis (methylthio) ethylene and 10 ml of ethanol is heated to reflux with stirring for 15 hours. After the reaction, ethanol is removed by distillation in vacuo. The tar residue was purified by silica gel column chromatography. 0.7 g is obtained

1- (3-methyl-5-isoxazolylmethyl) -3- (1-methyl-4-pyrazolylmethyl) -2- (nitromethylene) tetrahydro-

20 pyrimidine in the form of a viscous oil;

Example 16

<img file="CS255867B2_D0062.tif" />

(Compound No. 17)

6.6 g of finely divided 1-nitro-2,2-bis (methylthio) ethylene are mixed well with 7.5 g of 2- (2-chloro-5-pyridylmethylamino) ethanol. Heat the mixture at 110 to 120 ° C for 30 minutes until the methylmercaptan evolution ceases. The resulting oil was cooled to room temperature and purified by silica gel column chromatography. 1.7 g of 3- (2-chloro-5-pyridylmethyl) -2- (nitromethylene) oxazolidine are obtained. Melting point 123-124 ° C.

Example 1

<img file="CS255867B2_D0063.tif" />

(Compound No. 18)

Dissolve 2.6 g of potassium hydroxide in 20 ml of anhydrous ethanol. 3.7 g of 2- (2-methyl-5-pyrazinylmethylamino) ethanethiol are added to the solution obtained under a nitrogen atmosphere. The solution is cooled to 0 ° C and 3.0 g of 2,2-dichloro-1-nitroethylene is added dropwise at 0-10 ° C. After the addition, the mixture was stirred at 10 ° C for 1 hour. The ethanol was removed by distillation in vacuo, chloroform was added to the residue, and the chloroform layer was washed with 1% sodium hydroxide solution and water. The chloroform layer was then worked up in the usual manner to give 2.0 g of light yellow crystals of 3- (2-methyl-5-pyrazinylmethyl) -2- (nitromethylene) thiazolidine. Melting point 147-150 ° C. .

Example 18

<img file="CS255867B2_D0064.tif" />

(Compound No. 19)

A mixture of 4.7 g of N- (1,2,5-thiadiazol-3-ylmethyl) ethylenediamine, 3.4 g of nitroguanidine and 20 ml of water is stirred at 50-60 ° C for 1 hour and then at 70 ° C for 20 minutes. The resulting solution is then cooled slowly to 5 ° C to precipitate the desired product. The crystalline product is filtered off, washed with water and methanol and dried. 2.9 g of 1- (1,2,5-thiadiazol-3-ylmethyl) -2- (nitroimino) imidazolidine are obtained. Melting point 162-165 ° C.

Example 19

<img file="CS255867B2_D0065.tif" />

(Compound No. 20)

A mixture of 2.9 g of 2-nitroiminothiazolidine, 2.9 g of anhydrous potassium carbonate, 3.2 g

Of 2-chloro-5-pyridyl chloride and 50 ml of acetonitrile are heated to reflux for 5 hours with vigorous stirring. After the reaction, most of the acetonitrile was distilled off and water was added to the residue. The solid residue is filtered off and the crude product is recrystallized from ethanol. 3.8 g of the desired 3- (2-chloro-5-pyridylmethyl) -2- (nitroimino) thiazolidine are obtained. Mp 137-138 ° C.

Example 20

<img file="CS255867B2_D0066.tif" />

n-no₂

<img file="CS255867B2_D0067.tif" />

(Compound No. 21)

To a mixture of 1.3 g of finely divided 2-nitroiminoimidazolidine and 30 ml of absolute acetonitrile was added portionwise 0.4 g of sodium hydride (60% in oil) at room temperature, and the reaction mixture was stirred until hydrogen evolution ceased. A solution of 1.7 g of 2-chloro-5-thiazolylmethyl chloride in 10 ml of acetonitrile is then added dropwise at room temperature. After addition, the mixture was stirred at room temperature for 3 hours and then poured into ice water. The organic layer was extracted with dichloromethane and the dichloromethane extract was washed with 1% sodium hydroxide solution and water. After evaporation of the dichloromethane, the solid residue was washed with ether and dried. 1.4 g of the desired 1- (2-chloro-5-thiazolylmethyl) -2- (nitroimino) imidazolidine of melting point 147 DEG-150 DEG C. is obtained.

Example 21

<img file="CS255867B2_D0068.tif" />

(Compound No. 22)

Following the procedure described in Example 7, a gummy product was obtained from 2.3 g of ethyl nitro (t-tetrahydro-2H-1,3-thiazin-2-ylidene) acetate and 1.6 g of 2-chloro-5-pyridylmethyl chloride. This product was triturated in ethanol and the insoluble material was washed with hexane and then purified by silica gel column chromatography. 0.2 g of the desired ethyl 3- (2-chloro-5-pyridylmethyl) -tetrahydro-2H-1,3-thiazin-2-ylidene} acetate is obtained. Melting point 180-184 ° C.

Example 22

<img file="CS255867B2_D0069.tif" />

n-no₂

<img file="CS255867B2_D0070.tif" />

(Compound No. 23)

5.8 g of 2-imino-3- (4-pyridylmethyl) thiazolidine are added to 20 ml of concentrated sulfuric acid at a temperature of -5 to about 0 ° C. 6 ml of fuming nitric acid are then added dropwise to the solution at the same temperature. The reaction mixture is then stirred at a temperature between about 0 to 5 ° C for 30 minutes, and then the reaction mixture is poured into crushed ice. The mixture is extracted twice with dichloromethane and after usual work-up, 1.4 g of the desired 2-nitroimino-3- (4-pyridylmethyl) thiazolidine are obtained. Melting point 151-152 ° C.

Example 23

<img file="CS255867B2_D0071.tif" />

(Compound No. 27)

2.5 g of 1- (2-chloro-5-pyridylmethyl) -2- (nitromethylene) imidazolidine are dissolved in 40 ml of absolute dichloromethane and 10 ml of water are added. Subsequently, 1.6 g of bromine in 10 ml of dichloromethane are added to the reaction mixture over 10 minutes at 0-5 ° C with good stirring. The reaction mixture is then stirred for 10 minutes at 0-5 ° C, the crystalline product is filtered off, washed with cold water and a small amount of dichloromethane and dried. 2.5 g of 1- (2-chloro-5-pyridylmethyl) -2- (bromonitromethylene) iimidazolidine are obtained. Melting point 110-115 ° C (decomposition).

1- ϊ λ 1 ad 2 4

<img file="CS255867B2_D0072.tif" />

(£ L, No. 2'4

To a solution of 1,1'-methylimidazole in 50 ml of dichloromethane at a temperature below 0 ° C was added 3.1 g of phenol chlorine. The reaction mixture was stirred for 30 minutes at the same temperature and then 2.5 g of 1- (2-chloro-5-pyridylmethyl) - (2-nitromethylene) imidazolidine was added to the mixture, followed by stirring at room temperature for 24 hours, after which the reaction mixture was washed with water, 1% hydrochloric acid solution. acid and 1% sodium hydroxide solution. Distillation of dichloromethane gave glassy phenyl nitro [1- (2-chloro-5-pyridylmethyl) -3-phenoxycarbonylimidazolidin-2-ylidene] acetate. Yield 3.2 g. This product was then dissolved in 20 ml of dimethylformamide, 1.7 g of sodium carbonate was added to the solution, and the mixture was stirred for 3 days at room temperature. Water was then added and the organic layer was extracted with dichloromethane. The dichloromethane extract was washed with 1% sodium hydroxide solution and water. After evaporation of the dichloromethane, the residue is purified by chromatography on a silica gel column. 0.2 g of the desired phenylnitro- (2-chloro-5-pyridylmethyl) imidazolidin-2-ylidene] acetate is obtained. Mp 224-228 ° C (dec.).

Example 25

<img file="CS255867B2_D0073.tif" />

(Compound No. 31)

0.2 g of 60% sodium hydride in oil was added to a solution of 1.3 g of 1- (2-chloro-5-pyridylmethyl) -2-nitromethylenimidazolidine in 15 ml of absolute dimethylformamide, and the mixture was stirred at room temperature until completion. evolution of hydrogen. Then 0.9 g of 4-chlorobenzenesulfenyl chloride was added dropwise at 0 ° C. The reaction mixture was stirred at room temperature for 1 hour and then poured into ice water. The precipitated crystals are filtered off and recrystallized from ethyl acetate. 1.3 g of 1- (2-chloro-5-pyridylmethyl) -2-l are obtained (4-chlorophenylthio) nitromethyleneimidazolidine. M.p. 159-161 ° C.

Example 26

<img file="CS255867B2_D0074.tif" />

(Compound No. 32)

A solution of 0.9 g of benzenesulfonyl isocyanate in 10 ml of absolute dichloromethane is added dropwise to a solution of 1.3 g of 1- (2-chloro-5-pyridylmethyl) -2-nitromethylenimidazolidine in 25 ml of absolute dichloromethane at room temperature. The solution was then stirred at the same temperature for 2 hours and then evaporated under reduced pressure to about half the original volume of dichloromethane. The crystallized product is filtered off and washed with ether. 1 g of the desired N-benzene 52 is obtained

sulfonyl-2- [1- (2-chloro-5-pyridylmethyl) imidazolidin-2-ylidene] -2-nitroacetamide. Melting point 95-100 ° C.

Example 27

<img file="CS255867B2_D0075.tif" />

n-no₂ (Compound No. 33)

A mixture of 2.2 g of 2-nitroimino-1- (3-pyridylmethyl) imidazolidine, 1.6 g of 2-chloro-5-chloromethylpyridine, 1.4 g of anhydrous potassium carbonate in 30 ml of acetonitrile is heated under stirring for 16 hours under reflux. reflux condenser. The acetonitrile is then removed under reduced pressure, dichloromethane is added to the residue and the mixture is washed with water and 1% sodium hydroxide solution. The residue after removal of the dichloromethane under reduced pressure was purified by silica gel column chromatography. 2.1 g of 1- (2-chloro-5-pyridylmethyl-2-nitroimino-3- (3-pyridylmethyl) imidazolidine) is obtained, m.p.

Example 28

<img file="CS255867B2_D0076.tif" />

<img file="CS255867B2_D0077.tif" />

-iso (Compound # 34)

0.4 g of 60% sodium hydride in oil was added portionwise to a solution of 2.6 g of 1- (2-chloro-5-pyridylmethyl) -2-nitroiminoimidazolidine in 20 ml of absolute dimethylformamide. The reaction mixture was stirred at room temperature until evolution of hydrogen ceased. A solution of 1.5 g of isopropyl bromide in 5 ml of absolute dimethylformamide is then added dropwise at room temperature and the reaction mixture is stirred for 3 hours at room temperature. The reaction mixture was then poured into ice water and the precipitated crystals were filtered off. 1.5 g of 1- (2-chloro-5-pyridylmethyl) -3-isopropyl-2-nitroiminoimidazolidine are obtained. Melting point after recrystallization from ethanol 138-142 ° C.

Example 29

<img file="CS255867B2_D0078.tif" />

(Compound No. 35)

A mixture of 2.7 g of 3- (2-chloro-5-pyridylmethyl) -2-nitromethylenthiazolidine and 8 ml of butyric anhydride was stirred at 60 ° C for 8 hours under a nitrogen atmosphere. The volatiles were then removed by distillation under vacuum at 133.3 Pa while keeping the bath temperature below 60 ° C. The residue was dissolved in dichloromethane and the solution was washed with 1% sodium hydroxide solution. The dichloromethane layer was then purified by silica gel column chromatography. 0.15 g of a viscous oily 1- [3- (2-chloro-5-pyridylmethyl) thaisolidin-2-ylidene] -1-nitro-2-pentanone is obtained. η ^ θ = 1.6342.

In the same manner as described in the preceding examples, the compounds of formula (I) are obtained, which are listed in the following tables.

A sign in the columns in the columns ** _and means that n = 0 and in this case the corresponding ring structure represents a five-membered heterocyclic ring.

The following Table 1 summarizes the compounds in which X represents a sulfur atom, i.e. the formula I corresponds to the formula below

<img file="CS255867B2_D0079.tif" />

Table 1

<img file="CS255867B2_D0080.tif" />

<td>Compound</td><td></td><td></td><td>Binding position</td><td rowspan="2">Qi</td>

<td>č js 1 o</td><td>m</td><td>R</td><td>pyridine</td>

circle

<td> 36</td><td> 2</td><td>H</td><td> 5</td><td>2-F</td>

<td> 37</td><td> 3</td><td>H</td><td> 5</td><td>2-F</td>

<td> 38</td><td> 2</td><td>^CH3</td><td> 5</td><td>2-C1</td>

<td> 39</td><td> 2</td><td>H</td><td> 5</td><td>2-Br</td>

<td> 40</td><td> 2</td><td>H</td><td> 5</td><td>2,3-Cl₂</td>

<td> 41</td><td> 2</td><td>H</td><td> 5</td><td>2,3,4,6-F₄</td>

<td> 42</td><td> 2</td><td>H</td><td> 4</td><td>2-C1</td>

<td> 43</td><td> 3</td><td>H</td><td> 5</td><td>2-Br</td>

<td> 44</td><td> 2</td><td>H</td><td> 5</td><td>2-F, 3-C1</td>

<td> 45</td><td> 2</td><td>H</td><td> 2</td><td>3-C1</td>

<td> 46</td><td> 3</td><td>H</td><td> 2</td><td>5-C1</td>

<td> 47</td><td> 2</td><td>H</td><td> 2</td><td>3,5-Cl₂</td>

continuation of Table 1

Compound Binding position

<td>number</td><td>Л1</td><td>R</td><td>of the pyridine ring</td><td>^C1</td>

<td> 48</td><td> 3</td><td>H</td><td> 2</td><td>5-F</td>

<td> 49</td><td> 2</td><td>H</td><td> 2</td><td>6-Br</td>

<td> 50</td><td> 3</td><td>H</td><td> 3</td><td>2-C1</td>

<td> 51</td><td> 3</td><td>H</td><td> 3</td><td>5-Cl</td>

<td> 52</td><td> 2</td><td>H</td><td> 3</td><td>5-Br</td>

<td> 53</td><td> 2</td><td>H</td><td> 3</td><td>5-F</td>

<td> 54</td><td> 2</td><td> “^CH3</td><td> 5</td><td>2-F</td>

<td> 55</td><td> 3</td><td>H</td><td> 5</td><td>2.4 ~ CI₂</td>

<td> 56</td><td> 2</td><td>H</td><td> 5</td><td>2,4-Br₂</td>

<td> 57</td><td> 2</td><td>H</td><td> 4</td><td>2,6-F₂</td>

<td> 58</td><td> 3</td><td>H</td><td> 4</td><td>2-F</td>

<td> 59</td><td> 2</td><td>H</td><td> 4</td><td>2,6-Br₂</td>

<td> 60</td><td> 2</td><td>H</td><td> 5</td><td>2-F, 3-Br</td>

<td> 61</td><td> 2</td><td>H</td><td> 5</td><td>2-Cl, 3-F</td>

<td> 63</td><td> 2</td><td>H</td><td> 4</td><td> -</td>

<td> 64</td><td> 3</td><td>H</td><td> 4</td><td> -</td>

<td> 65</td><td> 2</td><td>H</td><td> 5</td><td>2-CH₃</td>

<td> 66</td><td> 2</td><td>H</td><td> 5</td><td>2-CH₃</td>

<td> 67</td><td> 2</td><td>H</td><td> 5</td><td> , ²-^C2^H5</td>

<td> 70</td><td> 3</td><td>H</td><td> 5</td><td>2-OCH₃</td>

<td> 71</td><td> 2</td><td>H</td><td> 5</td><td>²“^CH3</td>

<td> 73</td><td> 2</td><td>H</td><td> 5</td><td>2-Cl, 3-CH₃</td>

<td> 74</td><td> 2</td><td>-CH₃</td><td> 3</td><td> -</td>

<td> 75</td><td> 2</td><td>H</td><td> 5</td><td>2-CF₃</td>

<td> 76</td><td> 3</td><td>H</td><td> 5</td><td>²-CF₃</td>

<td colspan="2">continued Table 1 Compound</td><td rowspan="2">R</td><td rowspan="2">The bond position of the pyridine ring</td><td rowspan="2">^Q1</td>

<td>number</td><td>m</td>

<td> 79</td><td> 2</td><td>H</td><td> 5</td><td>2-CN</td>

<td> 80</td><td> 3</td><td>H</td><td> 5</td><td>2-CN</td>

<td> 90</td><td> 2</td><td>H</td><td> 5</td><td>2-OCH₂CF₃</td>

Compounds containing a sulfur atom in the meaning of the symbol X include, in addition to Table 1, the following Table 2.

Table 2

<img file="CS255867B2_D0081.tif" />

y-no₂

<td>Compound number</td><td>OF</td><td>R</td><td>R¹</td>

<td> 97</td><td></td><td>H</td><td>H</td>

<td> 98</td><td>F — pu</td><td>H</td><td>H</td>

<td> 99</td><td>in-</td><td>H</td><td>H</td>

<td> 101</td><td>cr</td><td>H</td><td>H</td>

<td> 102</td><td>HoC Q— N == Z</td><td>H</td><td>H</td>

<td> 103</td><td>^H3&lt;&lt; ^N--5</td><td>H</td><td>H</td>

<td> 105</td><td>^iCnrv N-0</td><td>H</td><td>H</td>

<td>R²</td><td>R³</td><td>R⁴</td><td>n</td><td>Y</td><td>Physical constants</td>

<td>H</td><td> -</td><td> -</td><td> 0</td><td>N</td><td></td>

<td>H</td><td> -</td><td> -</td><td> 0</td><td>N</td><td></td>

<td>H</td><td> -</td><td> -</td><td> 0</td><td>N</td><td></td>

<td> 0</td><td></td><td></td><td></td><td></td><td></td>

<td>H</td><td></td><td></td><td> 0</td><td>N</td><td></td>

<td>H</td><td> -</td><td> -</td><td> 0</td><td>N</td><td></td>

<td>H</td><td>H</td><td>H</td><td> 1</td><td>N</td><td></td>

<td>H</td><td></td><td></td><td> 0</td><td>N</td><td>mp 143-145 ° C</td>

continuation of Table 2

<img file="CS255867B2_D0082.tif" />

<img file="CS255867B2_D0083.tif" />

<td>R</td><td>R¹</td><td>R²</td><td>R³</td><td>R⁴</td><td>n</td><td>Y</td><td>Physical constants</td>

<td>H</td><td>H</td><td>H</td><td> -</td><td> -</td><td> 0</td><td>N</td><td></td>

<td>H</td><td>H</td><td>H</td><td>H</td><td>H</td><td> 1</td><td>N</td><td></td>

<td>H</td><td>H</td><td>H</td><td> -</td><td> -</td><td> 0</td><td>N</td><td></td>

<td>H</td><td>H</td><td>H</td><td> -</td><td> -</td><td> 0</td><td>N</td><td></td>

<td>H</td><td>H</td><td>H</td><td>H</td><td>H</td><td> 1</td><td>N</td><td></td>

<td>H</td><td>H</td><td>H</td><td> -</td><td> -</td><td> 0</td><td>N</td><td></td>

<td>H</td><td>H •</td><td>H</td><td> -</td><td> -</td><td> 0</td><td>CH</td><td></td>

<td>H</td><td>H</td><td>H</td><td> -</td><td> -</td><td> 0</td><td>CH</td><td></td>

<td>H</td><td>H</td><td>H</td><td>H</td><td>H</td><td> 1</td><td>CH</td><td></td>

<td>H</td><td>H</td><td>H</td><td></td><td></td><td> 0</td><td>CH</td><td></td>

continuation of Table 2

Compound number

116

<img file="CS255867B2_D0084.tif" />

117

<img file="CS255867B2_D0085.tif" />

118

<img file="CS255867B2_D0086.tif" />

119

<img file="CS255867B2_D0087.tif" />

131

<img file="CS255867B2_D0088.tif" />

134

<img file="CS255867B2_D0089.tif" />

137

<img file="CS255867B2_D0090.tif" />

138

<img file="CS255867B2_D0091.tif" />

141

<img file="CS255867B2_D0092.tif" />

R¹

R²^CH3

R³

R⁴

Physical constants

C-COCH₃ n ^⁵= 1,635 c-co

<img file="CS255867B2_D0093.tif" />

C-COOC₂H₅

C-COOC₂H₅

<img file="CS255867B2_D0094.tif" />

<img file="CS255867B2_D0095.tif" />

144 continuation of Table 2

Compound Physical;

ZRR number¹ R ^ R³ R⁴ η у constants

<td> 145</td><td>In P. N «= a /</td><td>H</td><td>H</td><td>H</td><td> -</td><td> -</td><td> 0</td><td>c-coo -</td>

<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 146</td><td>^НзСчу_. N — 0</td><td>H</td><td>H</td><td>H</td><td>H</td><td>H</td><td> 1</td><td>C-COOC₂H₅ n £⁴= = 1. 5978</td>

<td> 147</td><td>^нзс“О”</td><td>H</td><td>H</td><td>H</td><td> -</td><td> -</td><td> 0</td><td>C-COCH₃</td>

<td> 150</td><td>D- H₃CN— '</td><td>H</td><td>H</td><td>H</td><td> -</td><td> -</td><td> 0</td><td>CH</td>

<td> 151</td><td></td><td>H</td><td>H</td><td>H</td><td>H</td><td>H</td><td> 1</td><td>CH</td>

<td> 152</td><td>N = /</td><td>H</td><td>H</td><td>H</td><td>H</td><td>H</td><td> 1</td><td>CH</td>

<td> 154</td><td>'TV N — 0</td><td>H</td><td>H</td><td>H</td><td>H</td><td>H</td><td> 1</td><td>CH</td>

<td> 155</td><td></td><td>H</td><td>H</td><td>H</td><td>H</td><td>H</td><td> 1</td><td>CH</td>

<td> 156</td><td></td><td>H</td><td>H</td><td>H</td><td>H</td><td>H</td><td> 1</td><td>CH</td>

<td> 158</td><td> &gt;&gt;</td><td>H</td><td>H</td><td>H</td><td> -</td><td> -</td><td> 0</td><td>CH</td>

continuation of Table 2

<td>Compound number</td><td>OF</td><td>RR¹ R² R³ R⁴ η Y</td><td>Physical constants</td>

<td> 159 •</td><td>^N=\</td><td>HHH 0 CH</td><td></td>

<img file="CS255867B2_D0096.tif" />

N— S

<td colspan="2">Compounds containing</td><td>in meaning</td><td colspan="2">X is CH</td><td>2 sums up</td><td>following</td><td>Table 3:</td>

<td>T abu 1 к</td><td>and 3</td><td></td><td></td><td></td><td></td><td></td><td></td>

<td></td><td></td><td>OF</td><td colspan="2">R * П³ir⁽4&lt;_Rand - CH — N CH₂^H</td><td></td><td></td><td></td>

<td></td><td></td><td></td><td></td><td>y-no₂</td><td></td><td></td><td></td>

<td>Compound number</td><td>OF</td><td>R</td><td>R¹</td><td>2 3 R^OF R^J</td><td>R⁴ n</td><td>Y</td><td>Physical constants</td>

<td> 161</td><td>O-</td><td>CH</td><td> 3 ^H</td><td>H -</td><td> - 0</td><td>CH</td><td></td>

<td> 162</td><td>O^-</td><td>H</td><td>H</td><td>HH</td><td>H 1</td><td>CH</td><td></td>

<td> 163</td><td>^F-O^- '_N=/</td><td>H</td><td>H</td><td>H -</td><td> - 0</td><td>CH</td><td></td>

<td> 164</td><td></td><td>H</td><td>H</td><td>H -</td><td> - 0</td><td>CH</td><td></td>

<td> 166</td><td></td><td>H</td><td>H</td><td>H -</td><td> - 0</td><td>CH</td><td></td>

Table 3

Physical constants of continuation

Compound

Number

168

169

170

171 .

172

173

174

176

178

179

3 4

RR · * · R^OF R^J к η Y

<img file="CS255867B2_D0097.tif" />

continuation of Table 3

Compound No. Z

Physical constants

RR¹ R² R³ R⁴ η Y

180

<img file="CS255867B2_D0098.tif" />

<img file="CS255867B2_D0099.tif" />

<img file="CS255867B2_D0100.tif" />

<img file="CS255867B2_D0101.tif" />

<img file="CS255867B2_D0102.tif" />

<img file="CS255867B2_D0103.tif" />

182

<img file="CS255867B2_D0104.tif" />

<img file="CS255867B2_D0105.tif" />

<img file="CS255867B2_D0106.tif" />

<img file="CS255867B2_D0107.tif" />

<img file="CS255867B2_D0108.tif" />

<img file="CS255867B2_D0109.tif" />

184

<img file="CS255867B2_D0110.tif" />

<img file="CS255867B2_D0111.tif" />

<img file="CS255867B2_D0112.tif" />

<img file="CS255867B2_D0113.tif" />

<img file="CS255867B2_D0114.tif" />

<img file="CS255867B2_D0115.tif" />

185

<img file="CS255867B2_D0116.tif" />

<img file="CS255867B2_D0117.tif" />

<img file="CS255867B2_D0118.tif" />

<img file="CS255867B2_D0119.tif" />

<img file="CS255867B2_D0120.tif" />

<img file="CS255867B2_D0121.tif" />

<img file="CS255867B2_D0122.tif" />

<img file="CS255867B2_D0123.tif" />

186

<img file="CS255867B2_D0124.tif" />

<img file="CS255867B2_D0125.tif" />

<img file="CS255867B2_D0126.tif" />

<img file="CS255867B2_D0127.tif" />

<img file="CS255867B2_D0128.tif" />

<img file="CS255867B2_D0129.tif" />

188

<img file="CS255867B2_D0130.tif" />

<img file="CS255867B2_D0131.tif" />

<img file="CS255867B2_D0132.tif" />

<img file="CS255867B2_D0133.tif" />

<img file="CS255867B2_D0134.tif" />

<img file="CS255867B2_D0135.tif" />

189

<img file="CS255867B2_D0136.tif" />

<img file="CS255867B2_D0137.tif" />

<img file="CS255867B2_D0138.tif" />

<img file="CS255867B2_D0139.tif" />

<img file="CS255867B2_D0140.tif" />

<img file="CS255867B2_D0141.tif" />

<img file="CS255867B2_D0142.tif" />

<img file="CS255867B2_D0143.tif" />

<img file="CS255867B2_D0144.tif" />

<img file="CS255867B2_D0145.tif" />

<img file="CS255867B2_D0146.tif" />

<img file="CS255867B2_D0147.tif" />

<img file="CS255867B2_D0148.tif" />

191

<img file="CS255867B2_D0149.tif" />

<img file="CS255867B2_D0150.tif" />

<img file="CS255867B2_D0151.tif" />

<img file="CS255867B2_D0152.tif" />

<img file="CS255867B2_D0153.tif" />

<img file="CS255867B2_D0154.tif" />

<img file="CS255867B2_D0155.tif" />

<img file="CS255867B2_D0156.tif" />

<img file="CS255867B2_D0157.tif" />

<img file="CS255867B2_D0158.tif" />

<img file="CS255867B2_D0159.tif" />

192 continuation of Table 3

Physical constants

OF

RR¹ R² R³ R⁴ η Y

Compound number

<img file="CS255867B2_D0160.tif" />

η η h - - c-cooc₂h₅

<img file="CS255867B2_D0161.tif" />

196

<img file="CS255867B2_D0162.tif" />

<img file="CS255867B2_D0163.tif" />

<img file="CS255867B2_D0164.tif" />

<img file="CS255867B2_D0165.tif" />

<img file="CS255867B2_D0166.tif" />

<img file="CS255867B2_D0167.tif" />

Compounds in which X represents an oxygen atom are summarized in the following Table 4:

Table 4

OF

<img file="CS255867B2_D0168.tif" />

y-no₂

Compound No. Z

Physical

RR¹ R² R³ R⁴ η Y constants

199

200

<img file="CS255867B2_D0169.tif" />

201 continuation of Table 3

Compound No. Z

3 4

RR¹ R^of R^J R η Y

Physical constants

<td> 202</td><td></td><td>H</td>

<td> 203</td><td>^F3^C-/IN-</td><td>H</td>

<td> 204</td><td>N = /</td><td>H</td>

<td> 205</td><td>^C,- € r-</td><td>H</td>

<td> 207</td><td>^H1C~ O</td><td>H</td>

<td> 208</td><td>in</td><td>H</td>

Η H - - 0 CH

HH - - 0 CH

Η H - - 0 N

Η H - - ON

Η H - - ON

HH - - CH

<img file="CS255867B2_D0170.tif" />

N — 0

HH - - CH

HH - - 0 CH

<img file="CS255867B2_D0171.tif" />

HH - - CH

214 | Π_ ^H

SW

HH - - CH CH continued Table 4

Physical constants

Compound

<img file="CS255867B2_D0172.tif" />

RR¹ R² R³ R⁴ η Y

CH

CH

CH

CH

CH c-coo

<img file="CS255867B2_D0173.tif" />

c-what- (ch₂)₂ch₃

Table 5 summarizes the compounds of formula I of the following formula:

<img file="CS255867B2_D0174.tif" />

Г 65

Table 5

Η

<img file="CS255867B2_D0175.tif" />

<td>Compound number</td><td>m</td><td>R</td><td>The bond position of the pyridine ring</td><td>^Q1</td><td colspan="2">Physical constants</td>

<td> 225</td><td> 2</td><td>H</td><td> 3</td><td> -</td><td>tt</td><td>90-94 ° C (decomposition)</td>

<td> 226</td><td> 3</td><td>H</td><td> 3</td><td> -</td><td></td><td></td>

<td> 227</td><td> 2</td><td> “^CH3</td><td> 3</td><td> -</td><td></td><td></td>

<td> 230</td><td> 2</td><td>H</td><td> 4</td><td> -</td><td>tt</td><td>. Mp 154-157 ° C</td>

<td> 231</td><td> 3</td><td>H</td><td> . 4</td><td> -</td><td>tt</td><td>Mp 163-165 ° C</td>

<td> 232</td><td> 2</td><td>H</td><td> 2</td><td>5-C1</td><td></td><td></td>

<td> 233</td><td> 3</td><td>H</td><td> 5</td><td>2-F</td><td></td><td></td>

<td> 234</td><td> 2</td><td> “^CH3</td><td> 5</td><td>2-C1</td><td></td><td></td>

<td> 235</td><td> 2</td><td>H</td><td> 5</td><td>2-Br</td><td></td><td></td>

<td> 236</td><td> 2</td><td>H</td><td> 5</td><td>2-CH₃</td><td>tt</td><td>Mp 157-160 ° C</td>

<td> 237</td><td> 3</td><td>H</td><td> 5</td><td>^2_CH3</td><td>tt</td><td>155.5-158.5 ° C</td>

<td> 238</td><td> 2</td><td>H</td><td> 5</td><td>²“^C2^H5</td><td></td><td></td>

<td> 239</td><td> 2</td><td>H</td><td> 5</td><td>2-OCH₃</td><td></td><td></td>

<td> 241</td><td> 2</td><td>H</td><td> 5</td><td>2-SCH₃</td><td></td><td></td>

<td> 243</td><td> 2</td><td>H</td><td> 5</td><td>2-CN</td><td></td><td></td>

<td> 252</td><td> 2</td><td>H</td><td> 5</td><td> 2“^CF₃</td><td>tt</td><td>134-146 ° C</td>

<td> 253</td><td> 3</td><td>H</td><td> 5</td><td>2-CF₃</td><td></td><td></td>

<td> 261</td><td> 3</td><td>H</td><td> 5</td><td>2-OCH₂CF₃</td><td></td><td></td>

<td> 264</td><td> 2</td><td>H</td><td> 5</td><td>3-Br</td><td>tt</td><td>Mp 198-201 ° C</td>

<td> 265</td><td> 2</td><td>H</td><td> 2</td><td>⁵^CF3</td><td></td><td></td>

<td> 269</td><td> 2</td><td>H</td><td> 5</td><td>²,3-^C1₂</td><td></td><td></td>

<td> 270</td><td> 2</td><td>H</td><td> 5</td><td>2-Cl, 3-CH₃</td><td></td><td></td>

<td> 271</td><td> 2</td><td>H</td><td> 4</td><td>2,3,5,6-F₄</td><td></td><td></td>

Compounds in which Z is an optionally substituted pyridyl group and X 7 is an NR group are summarized in Table 6 below.

In this case, formula I is represented by the following general formula:

<img file="CS255867B2_D0176.tif" />

y-no₂

In Table 6, in column Q1, the pyridine ring is not substituted.

Table 6

<img file="CS255867B2_D0177.tif" />

Y-'WO₂

<img file="CS255867B2_D0178.tif" />

<img file="CS255867B2_D0179.tif" />

<img file="CS255867B2_D0180.tif" />

<img file="CS255867B2_D0181.tif" />

<img file="CS255867B2_D0182.tif" />

<img file="CS255867B2_D0183.tif" />

<img file="CS255867B2_D0184.tif" />

<td>О</td><td>О</td><td>no</td><td>no</td>

<td> 0</td><td> 0</td><td> 0</td><td> 0</td>

<td>Γ-</td><td>о</td><td>гЧ</td><td> 04</td>

<td>ΟΟ</td><td>со</td><td>СП</td><td></td>

<td>t — 4</td><td> 1—4</td><td>гЧ</td><td> 04</td>

<td>'З ·</td><td>О-</td><td>О</td><td>СП</td>

<td> 00</td><td>г- ·</td><td>&lt;т&gt;</td><td>О</td>

<td>гЧ</td><td>гЧ</td><td>гЧ</td><td> 04</td>

<td> 4-&gt;</td><td>«Р</td><td>-Р</td><td>«Р</td>

<td></td><td>Р</td><td>4J</td><td>Р</td>

<td>X</td><td> №</td><td></td><td>д</td><td>д.</td><td>х</td>

<td>υ</td><td>no</td><td>о</td><td>о</td><td>о</td><td>о</td>

<img file="CS255867B2_D0185.tif" />

<img file="CS255867B2_D0186.tif" />

<img file="CS255867B2_D0187.tif" />

<img file="CS255867B2_D0188.tif" />

<img file="CS255867B2_D0189.tif" />

<img file="CS255867B2_D0190.tif" />

<img file="CS255867B2_D0191.tif" />

<img file="CS255867B2_D0192.tif" />

<img file="CS255867B2_D0193.tif" />

<img file="CS255867B2_D0194.tif" />

<img file="CS255867B2_D0195.tif" />

<img file="CS255867B2_D0196.tif" />

<img file="CS255867B2_D0197.tif" />

<img file="CS255867B2_D0198.tif" />

<img file="CS255867B2_D0199.tif" />

<img file="CS255867B2_D0200.tif" />

<img file="CS255867B2_D0201.tif" />

<img file="CS255867B2_D0202.tif" />

<img file="CS255867B2_D0203.tif" />

<img file="CS255867B2_D0204.tif" />

<img file="CS255867B2_D0205.tif" />

<img file="CS255867B2_D0206.tif" />

<img file="CS255867B2_D0207.tif" />

<img file="CS255867B2_D0208.tif" />

<img file="CS255867B2_D0209.tif" />

<img file="CS255867B2_D0210.tif" />

<td rowspan="2">ΟΙ</td><td rowspan="2">СП д о</td><td rowspan="2">СП д о</td><td colspan="3">сп</td><td rowspan="2">сп Д О</td><td rowspan="2">д</td><td rowspan="2">СП д и</td><td rowspan="2">СП д о</td><td rowspan="2">СП д и</td><td rowspan="2">СП л и</td><td rowspan="2">СП л и</td><td rowspan="2">л</td><td rowspan="2">X</td><td rowspan="2">X</td><td rowspan="2">X</td>

<td>д и</td><td>д</td><td>д</td>

<td>гЧ</td><td>д</td><td>д</td><td>сп X О</td><td>д</td><td>д</td><td>д</td><td>д</td><td>д</td><td>д</td><td>д</td><td>д</td><td>л</td><td>X</td><td>X</td><td>X</td><td>X</td>

<td></td><td>д</td><td>со д о</td><td>д</td><td>д</td><td>д</td><td>д</td><td>д</td><td>д</td><td>д</td><td>д</td><td>д</td><td>л</td><td>л</td><td>X</td><td>X</td><td>X</td>

<img file="CS255867B2_D0211.tif" />

<td> ·*</td><td>сп</td><td>СП</td><td>м ·</td><td>м ·</td><td>ιη</td><td>ш</td><td>Ш</td><td>Ш</td><td>1Л</td><td>Ш</td><td>Ш</td><td>СП</td><td>ιη</td><td>ш</td><td>ш</td>

<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>сП</td><td>СП</td><td>СП</td><td></td><td></td><td></td><td></td>

<td></td><td></td><td></td><td></td><td></td><td></td><td> &lt;—1</td><td> ·—1</td><td>Р</td><td>Рч</td><td>X</td><td>ь</td><td></td><td></td><td>г-4</td><td> 1-4</td>

<td></td><td></td><td></td><td></td><td></td><td>Рч AND</td><td>О</td><td>no</td><td>X</td><td>О</td><td>ω</td><td>no</td><td></td><td>Рч</td><td>no</td><td>no</td>

<td> 1</td><td> 1</td><td> 1</td><td> 1</td><td> 1</td><td>ΟΙ</td><td> 04</td><td>OJ</td><td> 04</td><td> 04</td><td> 04</td><td> 04</td><td> 1</td><td> 04</td><td>ΟΙ</td><td>1 О1</td>

2-11 5 Η Η Н - - О СН_ОСН = СН

ТГш

Г-Г04О) &lt;огГ * · Г (Мо »οοσ&gt;)

О'г0404

О О)

Ой сч

СП ST со

OJ ю &lt;о со со

04 / σ \ со

СХ) о гЧ

СП СП οι

<img file="CS255867B2_D0212.tif" />

<img file="CS255867B2_D0213.tif" />

<img file="CS255867B2_D0214.tif" />

<img file="CS255867B2_D0215.tif" />

<img file="CS255867B2_D0216.tif" />

<img file="CS255867B2_D0217.tif" />

o oo

I CD ГX »

X³

<img file="CS255867B2_D0218.tif" />

<img file="CS255867B2_D0219.tif" />

о со оо ш

М¹СО • м

О см Q

С

<img file="CS255867B2_D0220.tif" />

<img file="CS255867B2_D0221.tif" />

<img file="CS255867B2_D0222.tif" />

<img file="CS255867B2_D0223.tif" />

Compound Binding position о х: 4L)&gt; о с • н Ό х:

□

0)

1/4

<img file="CS255867B2_D0224.tif" />

<img file="CS255867B2_D0225.tif" />

(й I см о I гм

О I см

О I см

О 'г-н СМ о о о

04 04

04-М *

ОО

0404

Г '

О

308 2-11 5 Η Η Н - - О СН₉ Cl CH tt 154-156 continued Table 6

Compound Binding position number. pyridine RR² R³ R⁴ n R⁷ Y Physical circle constant

<img file="CS255867B2_D0226.tif" />

tt 102-105

<img file="CS255867B2_D0227.tif" />

<img file="CS255867B2_D0228.tif" />

Г

I os r ~ «c:

Pí cn X

<img file="CS255867B2_D0229.tif" />

continuation of Table 6

Compound Binding position

<img file="CS255867B2_D0230.tif" />

-μ +&gt;

<img file="CS255867B2_D0231.tif" />

<img file="CS255867B2_D0232.tif" />

<img file="CS255867B2_D0233.tif" />

<img file="CS255867B2_D0234.tif" />

<img file="CS255867B2_D0235.tif" />

rСП СП

<img file="CS255867B2_D0236.tif" />

<img file="CS255867B2_D0237.tif" />

<img file="CS255867B2_D0238.tif" />

1Л

<img file="CS255867B2_D0239.tif" />

о

ТГ

СП

<img file="CS255867B2_D0240.tif" />

<img file="CS255867B2_D0241.tif" />

<img file="CS255867B2_D0242.tif" />

in

<img file="CS255867B2_D0243.tif" />

ГЧ СП

<img file="CS255867B2_D0244.tif" />

<img file="CS255867B2_D0245.tif" />

<img file="CS255867B2_D0246.tif" />

<img file="CS255867B2_D0247.tif" />

СП ч ·

СО о о rl

<img file="CS255867B2_D0248.tif" />

<img file="CS255867B2_D0249.tif" />

<img file="CS255867B2_D0250.tif" />

tn

<img file="CS255867B2_D0251.tif" />

<img file="CS255867B2_D0252.tif" />

<img file="CS255867B2_D0253.tif" />

<img file="CS255867B2_D0254.tif" />

in

<img file="CS255867B2_D0255.tif" />

1Л сП

XIX

<img file="CS255867B2_D0256.tif" />

<img file="CS255867B2_D0257.tif" />

<img file="CS255867B2_D0258.tif" />

<img file="CS255867B2_D0259.tif" />

<img file="CS255867B2_D0260.tif" />

<img file="CS255867B2_D0261.tif" />

<img file="CS255867B2_D0262.tif" />

<img file="CS255867B2_D0263.tif" />

<img file="CS255867B2_D0264.tif" />

СП in cn

<img file="CS255867B2_D0265.tif" />

СП ш сП ш сп continued Table 6

Compound Binding position number Q_r pyridine RR¹ R² R³ R⁴ n R⁷ γ Physical ^circle constants

Ш 00 1L

<img file="CS255867B2_D0266.tif" />

<img file="CS255867B2_D0267.tif" />

<img file="CS255867B2_D0268.tif" />

386 2-C1

<img file="CS255867B2_D0269.tif" />

<img file="CS255867B2_D0270.tif" />

<td> &gt;·</td><td colspan="2">о</td>

<td>л</td><td>л</td><td></td>

<td>N</td><td>М1)</td><td></td>

<td>Л</td><td> &gt;</td><td></td>

<td> &gt;</td><td> 0</td><td>д</td>

<td></td><td>д</td><td>л</td>

<td>it</td><td>• г4</td><td>Й</td>

<td>л</td><td>Ό</td><td>μ</td>

<td> 0</td><td>• н</td><td> 34</td>

<td>н</td><td></td><td></td>

<td> 0</td><td> &gt;1</td><td></td>

<td>Л</td><td>сь</td><td></td>

<td colspan="3">ко</td>

<td colspan="2">&gt; 1 34 «—1 5 to л</td><td>«-Ч сх</td>

<td>М</td><td></td><td></td>

<td>Д</td><td> (0</td><td></td>

<td>мО</td><td>д</td><td></td>

<td> &gt;</td><td>• н</td><td></td>

<td> 0</td><td>д</td><td> 0*</td>

<td>ю</td><td> (1)</td><td>Г-Н</td>

<td> (0</td><td>ю</td><td>(Л</td>

<td>ц</td><td>д</td><td>Ή</td>

<td> 34</td><td> 0</td><td>ю</td>

<td> 0</td><td>н</td><td></td>

<td>CU</td><td>ω</td><td></td>

in lD

<img file="CS255867B2_D0271.tif" />

oo σχ со со со сп

<td>ш</td><td>СП</td><td>1Л</td><td>ш</td>

<td>сп</td><td></td><td></td><td></td>

<td>щ</td><td></td><td>н</td><td>Н</td>

<td>no</td><td></td><td>о</td><td>О</td>

<td>см</td><td> 1</td><td>см</td><td>см</td>

о м · σχ со ко гσχ σχ сп сп

СП

UI

СМ

I см и. I см

КО о

О0 о &lt;зх о

<img file="CS255867B2_D0272.tif" />

<img file="CS255867B2_D0273.tif" />

<img file="CS255867B2_D0274.tif" />

oj οι гЧ

AND

<img file="CS255867B2_D0275.tif" />

<img file="CS255867B2_D0276.tif" />

circle of constant

In addition to Table 5, Table 7 summarizes the compounds of formula I corresponding to the formula

<img file="CS255867B2_D0277.tif" />

Table 8 then summarizes the compounds of formula I corresponding to the formula

<img file="CS255867B2_D0278.tif" />

Table 9 then summarizes the compounds of formula I that correspond to the formula

<img file="CS255867B2_D0279.tif" />

and Table 10 summarizes the compounds of formula I that correspond to the formula

<img file="CS255867B2_D0280.tif" />

Table 7

<img file="CS255867B2_D0281.tif" />

Compound Binding position. Het heterocycle

4Б4 N 2 l-i

Physical constants

mp 201-205 ° C

465

1-H

mp 183-185 ° C continued Table 7

<td>Compound C.</td><td>Het</td><td>The position of the heterocycle bond</td><td>Qi</td><td>R</td><td>m</td><td>Physical constants</td>

<td> 466</td><td>N</td><td> 3</td><td>1-H</td><td>H</td><td> 3</td><td></td>

<td> 467</td><td>N</td><td> 2</td><td>¹^CH3</td><td>H</td><td> 2</td><td></td>

<td> 468</td><td>N</td><td> 2</td><td>^1_CH3</td><td>H</td><td> 3</td><td>mp 207-213 ° C</td>

<td> 469</td><td>N</td><td> 2</td><td>¹“^C2^H5</td><td>H</td><td> 2</td><td></td>

<td> 470</td><td>N</td><td> 3</td><td> 1-^CH3</td><td>H</td><td> 3</td><td></td>

<td> 476</td><td>N</td><td> 3</td><td>1-H, 5-CH₃</td><td>H</td><td> 3</td><td></td>

<td> 477</td><td>N</td><td> 3</td><td>1-H, 5-CH₃</td><td>H</td><td> 2</td><td></td>

<td> 485</td><td>N</td><td> 3</td><td>1-CH₃, 5-C1</td><td>H</td><td> 3</td><td></td>

<td> 498</td><td>N</td><td> 3</td><td>1-CH₃, 5-CN</td><td>H</td><td> 2</td><td></td>

<td> 502</td><td>N</td><td> 3</td><td>1-CH₃.5-CF₃</td><td>H</td><td> 2</td><td></td>

Table 8

<img file="CS255867B2_D0282.tif" />

Compound Binding Position Physical

<td>C.</td><td>Het</td><td>heterocycle</td><td></td><td>R</td><td>m</td><td>constants</td>

<td> 513</td><td> 0</td><td> 3</td><td> -</td><td>H</td><td> 3</td><td></td>

<td> 514</td><td> 0</td><td> 4</td><td> -</td><td>H</td><td> 2</td><td></td>

<td> 515</td><td> 0</td><td> 4</td><td> -</td><td>H</td><td> 3</td><td></td>

<td> 516</td><td> 0</td><td> 4</td><td> -</td><td>^CH3</td><td> 2</td><td></td>

<td> 517</td><td> 0</td><td> 5</td><td> -</td><td>H</td><td> 3</td><td></td>

<td> 518</td><td> 0</td><td> 3</td><td> 5-^CH₃</td><td>H</td><td> 3</td><td>tt 186-188</td>

<td> 519</td><td> 0</td><td> 5</td><td>з-сн₃</td><td>H</td><td> 3</td><td>tt 200-201</td>

<td> 520 .</td><td> 0</td><td> 5</td><td>³“^C2^H5</td><td>H</td><td> 2</td><td></td>

continuation of Table 8

<td>Compound</td><td></td><td>Binding position</td><td></td><td></td><td></td><td>Physical</td>

<td>C.</td><td>Het</td><td>heterocycle</td><td>^C1</td><td>R</td><td>m</td><td>constants</td>

<td> 522</td><td> 0</td><td> 5</td><td>3-F</td><td>H</td><td> 3</td><td></td>

<td> 523</td><td> 0</td><td> 5</td><td>3-C1</td><td>H</td><td> 2</td><td></td>

<td> 524</td><td> 0</td><td> 5</td><td>3-Br</td><td>H</td><td> 2</td><td></td>

<td> 527</td><td> 0</td><td> 5</td><td>3-CN</td><td>H</td><td> 3·:</td><td></td>

<td> 528</td><td> 0</td><td> 5</td><td>³’^CF3</td><td>H</td><td> 2</td><td></td>

<td> 529</td><td> 0</td><td> 5</td><td> 3“^CF₃</td><td>H</td><td> 3</td><td>mp 177-180 ° C</td>

<td> 536</td><td> 0</td><td> 5</td><td>3-OCH₃</td><td>H</td><td> 3</td><td></td>

<td> 538</td><td> 0</td><td> 4</td><td>2,5- (CH₃)₂</td><td>H</td><td> 2</td><td></td>

<td> 539</td><td>WITH</td><td> 3</td><td> -</td><td>H</td><td> 3</td><td></td>

<td> 540</td><td>WITH</td><td> 4</td><td> -</td><td>H</td><td> 2</td><td></td>

<td> 541</td><td>WITH</td><td> 5</td><td> -</td><td>H</td><td> 2</td><td></td>

<td> 542</td><td>WITH</td><td> 3</td><td>⁵“^CII3</td><td>H</td><td> 3</td><td></td>

<td> 543</td><td>WITH</td><td> 5</td><td>^3_CH3</td><td>H</td><td> 2</td><td></td>

<td> 544</td><td>with</td><td> 5</td><td>3-F</td><td>H</td><td> 2</td><td></td>

<td> 545</td><td>with</td><td> 3</td><td>5-C1</td><td>H</td><td> 2</td><td></td>

<td> 546</td><td>with</td><td> 5</td><td>3-C1</td><td>H</td><td> 2</td><td></td>

<td> 547</td><td>with</td><td> 3</td><td>5-Br</td><td>H</td><td> 2</td><td></td>

<td> 550</td><td>N</td><td> 5</td><td>1-H</td><td>H</td><td> 2</td><td>mp 190-193 ° C</td>

<td> 551</td><td>N</td><td> 5</td><td>1-H</td><td>H</td><td> 3</td><td></td>

<td> 552</td><td>N</td><td> 4</td><td>1-H</td><td>H</td><td> 2</td><td>mp 196-198 ° C</td>

<td> 553</td><td>N</td><td> 4</td><td>1-H</td><td>^_CH3</td><td> 2</td><td></td>

<td> 554</td><td>N</td><td> 4</td><td>1-H</td><td>H</td><td> 3</td><td>mp 222-225 ° C</td>

<td> 555</td><td>N</td><td> 3</td><td>i-ch₃</td><td>H</td><td> 2</td><td>mp 212-215 ° C</td>

<td> 556</td><td>N</td><td> 4</td><td>1-Cg</td><td>H</td><td> 2</td><td>mp 179-180 ° C</td>

<td> 557</td><td>N</td><td> 4</td><td>^1_CH3</td><td>-CH₃</td><td> 3</td><td></td>

<td> 558</td><td>N</td><td> 5</td><td>¹^CH3</td><td>H</td><td> 2</td><td></td>

continuation of Table 8

<td>Compound</td><td></td><td>Binding position</td><td></td><td></td><td></td><td colspan="2">Physical</td>

<td>C.</td><td>Het</td><td>heterocycle</td><td> °1</td><td>R</td><td>m</td><td colspan="2">constants</td>

<td> 559</td><td>N</td><td> 4</td><td> 1-^C₂H₅</td><td>H</td><td> 2</td><td></td><td></td>

<td> 560</td><td>N</td><td> 4 · *</td><td>^1_C2^H5</td><td>H</td><td> 3</td><td>tt</td><td>145-148 [deg.] C</td>

<td> 572</td><td>N</td><td> 4</td><td>1-CF₃</td><td>H</td><td> 2</td><td></td><td></td>

<td> 573</td><td>N</td><td> 3*</td><td>i-ch₂cf₃</td><td>H</td><td> 2</td><td></td><td></td>

<td> 574</td><td>N</td><td> 4</td><td>i-ch₂cf₃</td><td>H</td><td> 2</td><td></td><td></td>

<td> 575</td><td>N</td><td> 5</td><td>ih, з-сн₃</td><td>H</td><td> 2</td><td>tt</td><td>183-185 ° C</td>

<td> 576</td><td>N</td><td> 5</td><td>ι-,, з-сн₃</td><td>H</td><td> 3</td><td></td><td></td>

<td> 577</td><td>N</td><td> 3</td><td>1-H, 5-Cl</td><td>H</td><td> 2</td><td></td><td></td>

<td> 578</td><td>N</td><td> 3</td><td>1-CH₃, 5-F</td><td>H</td><td> 2</td><td></td><td></td>

<td> 579</td><td>N</td><td> 3</td><td>1-СН₃, 5-C1</td><td>H</td><td> 2</td><td>tt</td><td>Mp 195-198 ° C</td>

<td> 580</td><td>N</td><td> 3</td><td>1-CH₃, 5-C1</td><td>H</td><td> 3</td><td>tt</td><td>Mp 222-224 ° C</td>

<td> 581</td><td>N</td><td> 3</td><td>1 “C₂H₅, 5-C1</td><td>H</td><td> 2</td><td></td><td></td>

<td> 583</td><td>N</td><td> 5</td><td>1-CH₃, 5-C1</td><td>H</td><td> 2</td><td></td><td></td>

<td> 584</td><td>N</td><td> 3</td><td>1-H, 5-CF₃</td><td>H</td><td> 2</td><td></td><td></td>

<td> 585</td><td>N</td><td> 3</td><td>1-CH₃.5-CF₃</td><td>H</td><td> 2</td><td></td><td></td>

<td> 586</td><td>N</td><td> 5</td><td>1-CH₃.5-CF₃</td><td>Й</td><td> 2</td><td></td><td></td>

<td> 587</td><td>N</td><td> 4</td><td>1,3,5- (CH₃)₃</td><td>H</td><td> .3</td><td>tt</td><td>Mp 192-194 ° C</td>

<td> 588</td><td>N</td><td> 5</td><td>1-CH₂CF₃</td><td>H</td><td> 2</td><td>tt</td><td>Mp 165-168 ° C</td>

Table 9

<img file="CS255867B2_D0283.tif" />

<td>Compound C.</td><td>Het</td><td>The position of the heterocycle bond</td><td>^Q1</td><td>R</td><td>m</td><td>Physical constants</td>

<td> 589</td><td> 0</td><td> . 4</td><td> -</td><td>H</td><td> 2</td><td></td>

<td> 590</td><td> 0</td><td> 5</td><td></td><td> 11</td><td> 2</td><td></td>

<td>continuation</td><td>Table 9</td><td></td><td></td><td></td><td></td><td></td>

<td>Compound</td><td></td><td>Binding position</td><td></td><td></td><td></td><td>Physical</td>

<td>C.</td><td>Het</td><td>heterocycle</td><td>^Q1</td><td>R</td><td>m</td><td>constants</td>

<td> 591</td><td> 0</td><td> 5</td><td> -</td><td>H</td><td> 3</td><td></td>

<td> 592</td><td> 0</td><td> 4</td><td>2-CH₃</td><td>H</td><td> 2</td><td></td>

<td> 593</td><td> 0</td><td> 5</td><td> 2-_CH₃</td><td>H</td><td> 2</td><td></td>

<td> 594</td><td> 0</td><td> 5</td><td> 2~^CH₃</td><td>H</td><td> 3</td><td></td>

<td> 595</td><td> 0</td><td> 5</td><td>⁴“^CH3</td><td>H</td><td> 2</td><td>mp 200-202 ° C</td>

<td> 596</td><td> 0</td><td> 5</td><td>⁴”^CH3</td><td>H</td><td> 3</td><td>mp 221-224 ° C</td>

<td> 597</td><td> 0</td><td> 5</td><td>2-F</td><td>H</td><td> 2</td><td></td>

<td> 598</td><td> 0</td><td> . 5</td><td>2-C1</td><td>H</td><td> 2</td><td></td>

<td> 599</td><td> 0</td><td> 5</td><td>2-C1</td><td>H</td><td> 3</td><td></td>

<td> 600</td><td> 0</td><td> 5</td><td> 2-^CF₃</td><td>H</td><td> 2</td><td></td>

<td> 603</td><td> 0</td><td> 5</td><td>2,4- (CH₃)₂</td><td>H</td><td> 2</td><td></td>

<td> 605</td><td>WITH</td><td> 4</td><td> -</td><td>H</td><td> 2</td><td>mp 213-216 ° C</td>

<td> 606</td><td>WITH</td><td> 4</td><td> -</td><td>H</td><td> 3</td><td>mp 181-183 ° C</td>

<td> 607</td><td>WITH</td><td> 5</td><td> -</td><td>H</td><td> 2</td><td>mp 169-174 ° C</td>

<td> 608</td><td>with</td><td> 5</td><td> -</td><td> “^CH3</td><td> 2</td><td></td>

<td> 610</td><td>with</td><td> 5</td><td> -</td><td>H</td><td> 3</td><td></td>

<td> 611</td><td>with</td><td> 4</td><td> 2-^CH₃</td><td>H</td><td> 2</td><td>mp 170-172 ° C</td>

<td> 612</td><td>with</td><td> 4</td><td>2-CH₃</td><td>H</td><td> 3</td><td>mp 203-206 ° C</td>

<td> 613</td><td>with</td><td> 5</td><td> 2-_CH₃</td><td>H</td><td> 2</td><td>mp 162-166 ° C</td>

<td> 614</td><td>with</td><td> 5</td><td>^2_CH3</td><td>-CH₃</td><td> 2</td><td></td>

<td> 615</td><td>with</td><td> 5</td><td> 2-^CH₃</td><td>-CH₃</td><td> 3</td><td></td>

<td> 618</td><td>with</td><td> 5</td><td> 4-_CH₃</td><td>H</td><td> 2</td><td></td>

<td> 619</td><td>with</td><td> 4</td><td>2-F</td><td>H</td><td> 2</td><td></td>

<td> 620</td><td>with</td><td> 4</td><td>2-C1</td><td>H</td><td> 2</td><td>mp 162-165 ° C</td>

<td> 621</td><td>with</td><td> 4</td><td>2-C1</td><td>H</td><td> 3</td><td>mp 190-194 ° C</td>

continuation of Table 9

<td>Compound C.</td><td>Het</td><td>The position of the heterocycle bond</td><td> 01</td><td>R</td><td>m</td><td>Physical constants</td><td></td>

<td> 622</td><td>WITH</td><td> 5</td><td>2-F</td><td>H</td><td> 3</td><td></td><td></td>

<td> 623</td><td>WITH</td><td> 5</td><td>2-Cl</td><td>H</td><td> 2</td><td>tt 191-192</td><td>° c</td>

<td> 624</td><td>WITH</td><td> 5</td><td>2-Cl</td><td>H</td><td> 3</td><td>tt 203-205</td><td>° c</td>

<td> 625</td><td>WITH</td><td> 5</td><td>2-Cl</td><td>-ch₃</td><td> 3</td><td></td><td></td>

<td> 627</td><td>WITH</td><td> 5</td><td>2,4-Cl₂</td><td>H</td><td> 2</td><td>tt 179-181</td><td>° c</td>

<td> 630</td><td>WITH</td><td> 4</td><td>2-CN</td><td>H</td><td> 2</td><td></td><td></td>

<td> 631</td><td>WITH</td><td> 5</td><td>2-CN</td><td>H</td><td> 2</td><td></td><td></td>

<td> 649</td><td>WITH</td><td> 5</td><td>2-CF₃</td><td>H</td><td> 2</td><td></td><td></td>

<td> 643</td><td>WITH</td><td> 4</td><td>2-OCH₃</td><td>H</td><td> 3</td><td></td><td></td>

<td> 644</td><td>WITH</td><td> 5</td><td>2-OCH₃</td><td>H</td><td> 3</td><td></td><td></td>

<td> 650</td><td>WITH</td><td> 5</td><td>2-CF₃</td><td>H</td><td> • 3</td><td></td><td></td>

<td> 655</td><td>N</td><td> 2</td><td>1-H</td><td>H</td><td> 2</td><td>tt 239-240</td><td>° c</td>

<td> 656</td><td>N</td><td> 4</td><td>1-H</td><td>H</td><td> .2</td><td></td><td></td>

<td> 657</td><td>N</td><td> 4</td><td>1-H</td><td>H</td><td> 3</td><td>tt 169-173</td><td>° c</td>

<td> 658</td><td>N</td><td> 2</td><td>i-ch₃</td><td>H</td><td> 2</td><td>tt 248-252</td><td>° c</td>

<td> 659</td><td>N</td><td> 5</td><td>1-CH₃</td><td>H</td><td> 2</td><td></td><td></td>

<td> 661</td><td>N</td><td> 5</td><td>1-H, 4-CH₃</td><td>H</td><td> 2</td><td></td><td></td>

<td> 662</td><td>N</td><td> 4</td><td>1-H, 2-F</td><td>H</td><td> 3</td><td></td><td></td>

<td> 663</td><td>N</td><td> 4</td><td>1-H, 2-Cl</td><td>H</td><td> 2</td><td></td><td></td>

<td> 666</td><td>N</td><td> 4</td><td>1,2- (CH₃)-₂</td><td>H</td><td> 2</td><td></td><td></td>

<td> 667</td><td>N</td><td> 4</td><td>1-CH₃, 2-CF₃</td><td>H</td><td> 2</td><td></td><td></td>

<td> 672</td><td>WITH</td><td> 5</td><td>2-CH₃</td><td>H</td><td> 4</td><td></td><td></td>

<td> 680</td><td>WITH</td><td> 5</td><td>2-Br</td><td>H</td><td> 3</td><td></td><td></td>

Table 10

<img file="CS255867B2_D0284.tif" />

Compound

C.

m Physical constant

681

682

<img file="CS255867B2_D0285.tif" />

<td>H</td><td> 2</td><td>mp 206-210 ° C</td>

<td>H</td><td> 3</td><td></td>

683

684

<img file="CS255867B2_D0286.tif" />

685

<img file="CS255867B2_D0287.tif" />

<td>H</td><td> 2</td><td>mp 265-267 ° C</td>

<td>H</td><td> 2</td><td></td>

<td>H</td><td> 3</td><td></td>

686

<img file="CS255867B2_D0288.tif" />

<img file="CS255867B2_D0289.tif" />

<img file="CS255867B2_D0290.tif" />

687

<img file="CS255867B2_D0291.tif" />

<img file="CS255867B2_D0292.tif" />

688 continued Table 10 Compound

<td>C.</td><td>OF</td><td>R</td><td>m</td><td>Physical constant</td>

<td> 689</td><td></td><td>H</td><td> 2</td><td></td>

<td> 690</td><td>at</td><td>H</td><td> 3</td><td></td>

<td> 691</td><td>With her</td><td>H</td><td> 2</td><td></td>

<td> 692</td><td>N — 0</td><td>H</td><td> 2</td><td>mp 221-225 ° C</td>

<td> 693</td><td>^F3^C. Y in N — 0</td><td>H</td><td> 2</td><td></td>

<td> 694</td><td>N - N ЛЛ H₃C</td><td>H</td><td> 2</td><td>mp 178-180 ° C</td>

<td> 695</td><td>N - N If H₃C</td><td>H</td><td> 3</td><td></td>

<td> 696</td><td>N - N Док F₃C</td><td>H</td><td> 2</td><td></td>

<td> 698</td><td>ГУ N— S</td><td>H</td><td> 2</td><td></td>

continuation of Table 10

Compound

No. ZR m Physical constants

<td colspan="5">5Г-1Г-</td>

<td> 699</td><td></td><td>H</td><td> 2</td><td></td>

<td> 700</td><td>IN.</td><td>H</td><td> 2</td><td></td>

<td> 701</td><td></td><td>H</td><td> 3</td><td></td>

<td> 702</td><td>n il</td><td>-CH₃</td><td> 2</td><td></td>

<td> 703</td><td>N - N ЧА</td><td>H</td><td> 2</td><td></td>

<td> 704</td><td>S — N lA</td><td> “^CH3</td><td> 3</td><td></td>

<td> 705</td><td>s — N in.</td><td>H</td><td> 2</td><td>mp 188-190 ° C</td>

<td> 706</td><td>S — N кА</td><td>H</td><td> 3</td><td>mp 207-210 ° C</td>

<td> 707</td><td>H₃C NS&gt; NS</td><td>H</td><td> 2</td><td></td>

<td> 708</td><td> ^/^CH3 N - &lt; &lt;A</td><td>H</td><td> 2</td><td></td>

R m

Physical constants of Table 10 continuation

Compound

C.

709

710

711

712

713

714

724

725

732

743

<img file="CS255867B2_D0293.tif" />

continuation of Table 10

Compound No.

Physical constants

744

<img file="CS255867B2_D0294.tif" />

mp 212-215 ° C

<img file="CS255867B2_D0295.tif" />

<img file="CS255867B2_D0296.tif" />

750

<img file="CS255867B2_D0297.tif" />

755

756

<img file="CS255867B2_D0298.tif" />

<img file="CS255867B2_D0299.tif" />

<img file="CS255867B2_D0300.tif" />

<img file="CS255867B2_D0301.tif" />

<img file="CS255867B2_D0302.tif" />

<img file="CS255867B2_D0303.tif" />

<img file="CS255867B2_D0304.tif" />

<img file="CS255867B2_D0305.tif" />

<img file="CS255867B2_D0306.tif" />

<img file="CS255867B2_D0307.tif" />

<td>H</td><td> 3</td><td></td>

<td>H</td><td> 2</td><td></td>

<td>H</td><td> 2</td><td></td>

<td>H</td><td> 2</td><td></td>

<td>H</td><td> 2</td><td>mp 185-187 ° C</td>

<td>H</td><td> 2</td><td>mp 216-217 ° C</td>

<td>H</td><td> 2</td><td>mp 188-189 ° C</td>

<img file="CS255867B2_D0308.tif" />

758 continuation of Table 10

Compound

<td>C.</td><td>OF</td><td>R</td><td>m</td><td colspan="2">Physical constants</td>

<td> 761</td><td>IN^е' Cl - &lt;/ Л_^N \</td><td>H</td><td> 2</td><td></td><td></td>

<td></td><td>ΌΙ</td><td></td><td></td><td></td><td></td>

<td> 762</td><td>O- Vn /</td><td>H</td><td> 2</td><td>tt 259-260</td><td>° C '</td>

<td> 763</td><td>O- \ = ^ N</td><td> -^CII3</td><td> 2</td><td>tt 173-174</td><td>° c</td>

<td> 764</td><td></td><td>if</td><td> 2</td><td>tt 216-218</td><td>° c</td>

765

766

<img file="CS255867B2_D0309.tif" />

768

9

<img file="CS255867B2_D0310.tif" />

770 continuation of Table 10

With a bite

C.

in

Physical constants

771

<img file="CS255867B2_D0311.tif" />

773

<img file="CS255867B2_D0312.tif" />

777

<img file="CS255867B2_D0313.tif" />

784

<img file="CS255867B2_D0314.tif" />

ři

785

<img file="CS255867B2_D0315.tif" />

786

<img file="CS255867B2_D0316.tif" />

<img file="CS255867B2_D0317.tif" />

788

<img file="CS255867B2_D0318.tif" />

H

789

<img file="CS255867B2_D0319.tif" />

tt i 7

<img file="CS255867B2_D0320.tif" />

790

R m

Physical constants of Table 10 continuation

Compound

No. Z.

<img file="CS255867B2_D0321.tif" />

792

793

<img file="CS255867B2_D0322.tif" />

NN

<img file="CS255867B2_D0323.tif" />

794 №N

Cl --- (/ Ъ-In addition to Tables 5 to 10 s) ι1 η υ, Table 11 of the compound of formula (I) in which X is N4 &lt;

га X я л • и ь

<img file="CS255867B2_D0324.tif" />

<img file="CS255867B2_D0325.tif" />

I со

О ш о 00

<img file="CS255867B2_D0326.tif" />

о со

<img file="CS255867B2_D0327.tif" />

807

<img file="CS255867B2_D0328.tif" />

<img file="CS255867B2_D0329.tif" />

&gt; 1 + JQ

P ω G 0 Λ4 continuation of Table 11

<img file="CS255867B2_D0330.tif" />

824

<img file="CS255867B2_D0331.tif" />

<img file="CS255867B2_D0332.tif" />

<img file="CS255867B2_D0333.tif" />

<img file="CS255867B2_D0334.tif" />

со г- &lt;

I сю

<img file="CS255867B2_D0335.tif" />

<img file="CS255867B2_D0336.tif" />

<img file="CS255867B2_D0337.tif" />

<img file="CS255867B2_D0338.tif" />

<img file="CS255867B2_D0339.tif" />

<img file="CS255867B2_D0340.tif" />

<img file="CS255867B2_D0341.tif" />

<img file="CS255867B2_D0342.tif" />

<img file="CS255867B2_D0343.tif" />

<img file="CS255867B2_D0344.tif" />

<img file="CS255867B2_D0345.tif" />

<img file="CS255867B2_D0346.tif" />

<img file="CS255867B2_D0347.tif" />

<img file="CS255867B2_D0348.tif" />

0) ю а о г— &lt;ω

<img file="CS255867B2_D0349.tif" />

<img file="CS255867B2_D0350.tif" />

<img file="CS255867B2_D0351.tif" />

1Л

CXJ

Г '00 ст »

СЧ | rj СХ | со 00

830 и о

М¹ м ·

Ή&gt; ч С Л д мп d 34 Л • и ω N q&gt; ι О Рч 34 см ч *

<img file="CS255867B2_D0352.tif" />

<td></td><td colspan="2"></td>

<td>СП</td><td></td><td></td>

<td> « :</td><td> 1</td><td> 1</td>

<td>см</td><td></td><td></td>

<td>X</td><td>X</td><td>X</td>

<img file="CS255867B2_D0353.tif" />

<img file="CS255867B2_D0354.tif" />

<img file="CS255867B2_D0355.tif" />

<img file="CS255867B2_D0356.tif" />

<img file="CS255867B2_D0357.tif" />

о О

СП гЧ см

AND

КО см

<img file="CS255867B2_D0358.tif" />

<img file="CS255867B2_D0359.tif" />

continued table

СП оо

<img file="CS255867B2_D0360.tif" />

<img file="CS255867B2_D0361.tif" />

<img file="CS255867B2_D0362.tif" />

<img file="CS255867B2_D0363.tif" />

<img file="CS255867B2_D0364.tif" />

СП

<img file="CS255867B2_D0365.tif" />

<img file="CS255867B2_D0366.tif" />

R С ri VQ д: • н&gt; 1 μ с + j tn co л:

continuation of Table 11

<img file="CS255867B2_D0367.tif" />

<img file="CS255867B2_D0368.tif" />

<img file="CS255867B2_D0369.tif" />

o &lt;nin

4040 co00

<img file="CS255867B2_D0370.tif" />

<img file="CS255867B2_D0371.tif" />

oo

Ю rH

AND

1Л

- Continuation of Table 11

<img file="CS255867B2_D0372.tif" />

The following are typical examples illustrating the preparation of the starting compounds of formula (II).

Example 30

<img file="CS255867B2_D0373.tif" />

CH₂-NH (CH₂)₃NH 2 g of trimethylenediamine is dissolved in 120 ml of acetonitrile and a solution of 14.8 g of 5-chloromethyl-2-methylthiazole in 30 ml of acetonitrile is added dropwise at 10 to 15 ° C. After the addition, the mixture is stirred for some time at 30-40 ° C and then 8 g of 50% aqueous sodium hydroxide solution are added. The volatiles were then removed in vacuo at a bath temperature of less than 50 ° C at 666.6 Pa. The inorganic fractions were removed from the residue by filtration. 16.7 g of N- (2-methyl-5-thiazolylmethyl) trimethylenediamine (about 90% pure) are obtained in the form of a colorless oil.²² = 1,5126.

Example 31

<img file="CS255867B2_D0374.tif" />

ch₂-nh (ch₂)₂nh g of ethylenediamine is dissolved in 120 g of acetonitrile and a solution of 17.6 g of 5-bromomethyl-3-methylisoxazole in 30 ml of acetonitrile is added dropwise at 5-10 ° C. After addition, the mixture was stirred for 1 hour while maintaining the temperature of the reaction system at about 20 ° C. Thereafter, the maximum proportion of volatile components is evaporated in vacuo (less than 2 mm Hg) while maintaining the bath temperature at 20 ° C. Ice water was added to the residue and the mixture was extracted with dichloromethane. The dichloromethane layer was dried and the dichloromethane was distilled off under reduced pressure. 10.0 g of N- (3-methyl-5-isoxazolylmethyl) ethylenediamine (purity about 95%) are obtained as a colorless oil.

NMR spectrum (delta in chloroform):

NH, NH₂ : 1.47 (ppm) - CH₂CH₂-: 2.23 -CH₃ : 2,7

-CH₂-: 5.8 hetero-H: 5.9

Example 32

<img file="CS255867B2_D0375.tif" />

ch₂-nh (ch₂)₃nh₂

At room temperature, 11 g of 1-methyl-4-pyrazolecarbaldehyde is slowly added to 37 g of ethylenediamine in 150 ml of absolute acetonitrile. A molecular sieve having a pore size of 4x10 m is then added to the reaction mixture and a dehydrating agent is added to the solution. The mixture was stirred at room temperature for 2 hours and then filtered. The acetonitrile was distilled off from the filtrate under reduced pressure. 100 ml of ethanol and then 4 g of sodium borohydride are added in portions at room temperature. The reaction mixture was then stirred at room temperature for 2 hours and ethanol was distilled off under reduced pressure. Water was added to the residue and the mixture was extracted with dichloromethane. The solvent was distilled off from the dichloromethane layer and the residue was distilled under vacuum. 10 g of N- (1-methyl-4-pyrazollymethyl) trimethylenediamine are obtained in the form of a colorless oil. Boiling point 120 to 125 ° C / 106.7 Pa.

Table 12 summarizes the novel compounds of formula (II) obtained in the same manner as described in Examples 30 to 32.

Table 12

R

H₂N- (CH₂) -nh-ch-z

Physical constants

<img file="CS255867B2_D0376.tif" />

<img file="CS255867B2_D0377.tif" />

1,5523

<img file="CS255867B2_D0378.tif" />

Cl n = 1.5495

3. n "^at = 1.4683 continuation of Table 12 of R

Physical constants

<img file="CS255867B2_D0379.tif" />

H

<img file="CS255867B2_D0380.tif" />

1,5335

<img file="CS255867B2_D0381.tif" />

<img file="CS255867B2_D0382.tif" />

= 1,5230

<img file="CS255867B2_D0383.tif" />

mp 125-127 ° C / 133 Pa

H₃C

<img file="CS255867B2_D0384.tif" />

^_CH3

tv 133-135 ° C / 160 Pa

<img file="CS255867B2_D0385.tif" />

<td> 3</td><td>n^{20 May n}D</td><td> = 1,5251</td>

<td> 2</td><td></td><td></td>

<td> 2</td><td> 20 ⁿD</td><td> = 1,4940</td>

<td> 3</td><td> „20 ⁿD</td><td> = 1,4904</td>

100 ALIGN! continuation of Table 12

R m Physical constants

<td>H₃CC^H3</td><td>H</td><td> 3</td><td></td>

<td>CH₃</td><td></td><td></td><td></td>

<td>Vk '</td><td>H</td><td> 2</td><td>Пр³ - 1,5003</td>

<td>Okay</td><td>H</td><td> 3</td><td></td>

<td>vc</td><td>H</td><td> 2</td><td>n³⁷ = 1,5160</td>

<td>/ CH₃at</td><td>H</td><td> 3</td><td>n³⁷ = 1,5130</td>

<td>rf</td><td>H</td><td> 2</td><td>n³⁰ » 1,5722</td>

<td>Vx</td><td>H</td><td> 2</td><td></td>

<td>Uk</td><td>H</td><td> 3</td><td></td>

<img file="CS255867B2_D0386.tif" />

<img file="CS255867B2_D0387.tif" />

<img file="CS255867B2_D0388.tif" />

<td>H</td><td> 2</td><td>n³⁴ = 1,5205</td>

<td>H</td><td> 2</td><td>n³⁴ = 1,5691</td>

<td>H</td><td> 3</td><td></td>

continuation of Table 12

101

<td>OF</td><td>R</td><td>m</td><td>Physical constants</td>

<td>Ix</td><td>H</td><td> 2</td><td></td>

<td>F₃&lt;Z ^{S 4}</td><td>* H</td><td> 2</td><td></td>

<td>Ж</td><td>. H</td><td> 2</td><td>n²⁰ = 1,5788</td>

<td>at</td><td>H</td><td> 3</td><td></td>

<td>CH₃ 1</td><td>H</td><td> 2</td><td></td>

<td>»-Й and/- </td><td>H</td><td> 2</td><td></td>

<td>HoC SN Lb I =_N</td><td>H</td><td> 2</td><td></td>

<td>at</td><td>H ·</td><td> 2</td><td>n²⁰ = 1,5457</td>

<td></td><td>H</td><td> 2</td><td></td>

<td></td><td>H</td><td> 3</td><td></td>

<td>HnC in</td><td>H</td><td> 2</td><td></td>

102 continuation of Table 12

ZR m

Physical constants

<img file="CS255867B2_D0389.tif" />

<img file="CS255867B2_D0390.tif" />

Example 33

<img file="CS255867B2_D0391.tif" />

<img file="CS255867B2_D0392.tif" />

ch₂nh- (ch₂)₃-sn

A solution of 14.2 g of 6-chloronicotinaldehyde, 7.7 g of 2-aminoethanthiol and 80 ml of benzene is heated with stirring for 5 hours to remove water as an azeotropic mixture. After the reaction, benzene was distilled off under reduced pressure, and further volatiles were removed at 1 mm Hg and 70 ° C, yielding 18 g of 2- (2-chloro-5-pyridyl) thiazolidine as a residue. 10 g of 2- (2-chloro-5-pyridyl) thiazolidine are dissolved in 100 ml of ethanol and sodium borohydride is added. The reaction mixture was gradually heated to reflux with stirring and then refluxed for 1 hour. Ethanol was then distilled off under reduced pressure and chloroform was added to the residue. The insolubles were filtered off and the chloroform layer was washed with water and dried. The chloroform was then distilled off under reduced pressure. 8.3 g of the desired N- (2-chloro-5-pyridylmethyl) -2-aminoethanethiol are obtained. n + - 1.5917.

Example 34

<img file="CS255867B2_D0393.tif" />

CH₂NH- (CH₂)₃-SH

A solution consisting of 12.1 g of 6-methylnicotinaldehyde, 4.1 g of 3-aminopropanethiol and 120 m -1.

of benzene is heated to reflux for 5 hours with stirring, the resulting water being removed as an azeotropic mixture. After completion of the reaction, benzene is distilled off under reduced pressure, and then the remaining volatiles are distilled off at 133 Pa and at 70 ° C. 16.5 g of 3-pyridyltetrahydrothiazine are obtained in the form of a residue. Then, 10 g of 3-pyridyltetrahydrothiazine is dissolved in 100 ml of ethanol and sodium borohydride is added to the solution. The mixture was gradually heated under stirring to reflux and then refluxed for 1 hour. Ethanol was distilled off under reduced pressure, chloroform was added to the residue, and insolubles were removed by filtration. The chloroform layer was washed with water and dried. By distilling off the chloroform under reduced pressure, 6.2 g of the desired compound, i.e. N- (3-pyridyl) -3-aminopentanethiol, were obtained. n = 1.5733.

In the same manner as described in Examples 33 and 34, compounds of the following formula were also prepared

<img file="CS255867B2_D0394.tif" />

(No II)

N- (2-chloro-5-pyridylmethyl) -3-aminopropanethiol (η_β = 1,5890)

103

<img file="CS255867B2_D0395.tif" />

ch₂-nh- (ch₂)₃-sh η * = 1.5748 (No. II-4)

<img file="CS255867B2_D0396.tif" />

сн₂-nh (ch₂)₂-sh

<img file="CS255867B2_D0397.tif" />

1.5817 (s. II-5)

Example 35

<img file="CS255867B2_D0398.tif" />

CH₂NH- ÍCH₂) 2-NH₂ g of ethylenediamine is dissolved in 200 ml of benzene and 21.6 g of 5-formylpyrimidine are added at room temperature. The reaction mixture was then heated to reflux and maintained at reflux for 3 hours while removing the water formed as an azeotrope. After the reaction, benzene and excess ethylenediamine are distilled off under reduced pressure. The residue was dissolved in 200 ml of ethanol. 8.4 g of sodium borohydride were added portionwise to the solution at room temperature, followed by stirring at room temperature for 5 hours. Ethanol was distilled off under reduced pressure and 100 ml of dichloromethane were added to the residue. The dichloromethane solution was separated, the dichloromethane was distilled off and, after distillation, N- (5-pyrimidinylmethyl) ethylenediamine (25.8 g) was obtained as a colorless oil; Distillation is carried out under reduced pressure. n_D = 1,5532.

Example 36

<img file="CS255867B2_D0399.tif" />

g of ethylenediamine is dissolved in 200 ml of acetonitrile and 12.9 g of pyrazinylmethyl chloride are added thereto at a temperature of 5 to 10 ° C. After addition, the mixture was stirred at room temperature for 1 hour. 8 g of a 50% aqueous sodium hydroxide solution are then added and the volatiles are removed at a bath temperature of 60 [deg.] C. and at 1 mmHg. The inorganic salt is filtered off.

14.1 g of N- (pyrazinylmethyl) ethylenediamine are obtained in the form of a colorless oil. ηθ = 1.5359.

Example 37

<img file="CS255867B2_D0400.tif" />

ch₂ch₂- (ch₂)₃-nh₂

3.5 g of 5-trifluoromethylpicolinaldehyde is added dropwise at room temperature to a solution of 7.4 g of trimethylenediamine in 70 ml of benzene. After the addition, the reaction mixture is gradually heated to reflux with stirring and refluxed for 2 hours with azeotropic removal of water. Then benzene is distilled off under reduced pressure and the residue is then dissolved in 100 ml of ethanol. 0.9 g of sodium borohydride is slowly added with stirring at 10 to 15 ° C. The reaction mixture was stirred at room temperature for 2 hours. Ethanol is distilled off at a temperature not exceeding 30 ° C. Dichloromethane was added to the residue and the dichloromethane soluble portion was separated. The dichloromethane was distilled off under reduced pressure and the volatiles were removed at 133.3 Pa at a temperature below 60 ° C. 3.5 g of N- (5-trifluoromethyl-2-pyridylmethyl) trimethylenediamine are obtained in the form of a colorless oil. η²θ = 1.4651

104

CH₃

AND ³ ch₂nhch₂chnh₂

<img file="CS255867B2_D0401.tif" />

Example 38

A solution of 8.1 g of 2-chloro-5-chloromethylpyridine in 30 ml of acetonitrile was added dropwise to the mixture.

14.8 g of 1,2-diaminopropane, 5 g of 40% sodium hydroxide solution and 100 ml of acetonitrile over 2 hours at 0 ° C with vigorous stirring. After stirring for a short time at room temperature, acetonitrile, water and excess 1,2-diaminopropane are removed under reduced pressure. The inorganic salt is filtered off and the filtrate is the desired product, i.e. 9.3 g of 2-amino-1- (217 g).

(chloro-5-pyridylmethylamino) propane. η_β = 1,5450.

In the same manner as described in Example 38, the following compounds were prepared:

N-methyl-N'-3-pyridylmethylethylenediamine, boiling point 140 ° C / 333.3 Pa;

2-amino-2-methyl-1- (3-pyridylmethylamino) propane, bp 115 ° C / 200 Pa;

2-Aminomethyl-2-methyl-1- (1-methyl-4-pyrazolylmethyl) propane;_D « 1,5109.

Example 39 _/___XCH₂NHCH₂CH₃NHCH₂—V | χτ^NCl · ^N

A solution of 18.6 g of N- (2-chloro-5-pyridylmethyl) ethylenediamine, 11 g of 1-methylpyrazole-4-carbaldehyde in 150 ml of benzene is stirred on a warm water bath. After a short time, water is separated from the solution and this means that the Schiff base has formed. The benzene and water are then removed under reduced pressure and 100 ml of ethanol are added to the residue. A solution of 3.8 g of sodium borohydride was added portionwise at room temperature and the reaction mixture was stirred for 1 day. After removal of the ethanol under reduced pressure, the residue was dissolved in dichloromethane and the dichloromethane solution was washed with water. Treatment of the dichloromethane solution in the usual manner affords the desired intermediate, i.e. N- (2-chloro-5-pyridylmethyl) -1 '- (1-methyl-4-pyrazolyl-20-methyl) ethylenediamine as a viscous oil. Yield 23.5 g. N * = 1.5655.

In the same manner as described in Example 39, the following compounds were prepared:

N- (3-pyridylmethyl) -1 '- (2-chloro-5-pyridylmethyl) ethylenediamine, n_D « 1,5846;

N- (3-methyl-5-isoxazolylmethyl) -1 '- (1-methyl-4-pyrazolylmethyl) trimethylenediamine, n³⁰ = 1,5224.

Example 40

<img file="CS255867B2_D0402.tif" />

ch₂nhch₂ch₂oh

105

A solution of 7 g of 5-bromomethyl-3-methylisoxazole in 20 ml of acetonitrile is added dropwise to the solution.

12.2 g of 2-aminoethanol in 100 ml of acetonitrile at a temperature below 10 ° C. The reaction mixture was stirred at room temperature and then acetonitrile and excess 2-aminoethanol were removed under reduced pressure. Chloroform was added to the residue, and the chloroform solution was washed with a small amount of water. Treatment of the chloroform solution in the usual manner affords the desired 2- (3-methyl-5-isoxazolylmethylamine) ethanol. Yield 4.4 g. Η²θ = 1.5130.

In the same way as described in Example 40 of Nina:

3- (2-chloro-5-pyridylmethylamino) propanol, n_D for example, the following compounds are obtained = 1.5391;

N- (4-pyridylmethyl) ethanolamine, bp 148-150 ° C / 400 Pa.

Example 41

<img file="CS255867B2_D0403.tif" />

To a solution of 15.6 g of 2- (3-methyl-5-isoxazolylmethylamino) ethanol in 100 ml of chloroform was added a catalytic amount of pyridine and then at room temperature 15 g of thionyl chloride. After the addition, the mixture was heated under reflux for 30 minutes and then the volatiles were removed in vacuo. 136 DEG-139 DEG C., as the hydrochloride salt.

An ethanolic solution of potassium hydrogen sulphide is prepared by saturating a solution of 13.4 g of potassium hydroxide in 120 ml of ethanol with hydrogen sulfide gas. The above hydrochloride was added portionwise to the resulting solution at 25-30 ° C with stirring. The reaction mixture was slowly warmed and then stirred at 60 ° C for 2 hours. After cooling to room temperature, the inorganic salt is rapidly aspirated and the solvent is removed under reduced pressure.

12.9 g of 2- (3-methyl-5-isoxazolylamino) ethanethiol are obtained as an oil. η_β = 1,5490.

For example, the following compound is obtained in the same manner as described in Example 41:

2- (2-methyl-5-pyrazinylamino) ethyl mercaptan, n²⁸ = 1,5581.

Example 42 / N NO₂

N

<img file="CS255867B2_D0404.tif" />

2.5 g of sodium hydride (60%) in oil was added in small portions to a solution of 3.9 g of 2-nitroiminoimidazolidine in absolute dimethylformamide. After the addition, the mixture is stirred until the evolution of hydrogen ceases. The reaction mixture was cooled to -5 ° C and 4.7 g of phenyl chloroformate was added dropwise at a temperature below 0 ° C. The reaction mixture was then stirred for 1 hour at room temperature, then poured into ice water, adjusted to pH 7 and extracted with dichloromethane. Removal of the dichloromethane and washing with ether gave white crystals of the title compound. 5.1 g of 1- (phenoxycarbonyl) -2-nitroiminoimidazolidine are obtained. Melting point 171-175 ° C.

106

In the same manner as described in Example 42, for example, the following compound is prepared:

1-(2_/184 DEG-186 DEG C. 4-dichlorobenzoyl) -2- (nitroimino) imidazolidine.

Examples illustrating biological activity:

In the following:

the biological activity tests were as reference compounds

Comparative compound

Al

<img file="CS255867B2_D0405.tif" />

i-ch₂

<img file="CS255867B2_D0406.tif" />

chno₂ (the compound described in German patent specification no.

514 402).

Comparative compound

A-2

<img file="CS255867B2_D0407.tif" />

(a compound disclosed in Japanese Published Patent Application No. 196,877 / 1984).

Comparative compound

A-3

<img file="CS255867B2_D0408.tif" />

CH₂

<img file="CS255867B2_D0409.tif" />

chno₂ (a compound disclosed in Japanese Published Patent Application No. 196,877 / 1984).

Comparative compound

A-4 (compound described in

Can. J. Chem.

<img file="CS255867B2_D0410.tif" />

Example 43

Test for Nephotettix cincticeps (strain resistant to organic phosphorus compounds)

Solvent: Emulsifier:

parts by weight of xylene part by weight of polyoxyethylene alkylphenyl ether

A suitable active ingredient is prepared by mixing 1 part by weight of the active ingredient with the abovementioned amount of solvent containing the abovementioned amount of emulsifier. The mixture is diluted with water to a predetermined concentration.

107

Rice plants of about 10 cm height grown in pots of 12 cm diameter are sprayed with 10 ml / pot per preparation of the individual active compounds tested, diluted with water to the desired concentration. The spraying layer is allowed to dry and each pot is covered with a protective wire mesh in the form of a cylinder 7 cm in diameter and 14 cm high. 30 female Nephotettix concticeps female imagues which are resistant to organic phosphorus compounds are then placed inside. Each pot was placed in a constant temperature room, and two days later the number of killed insects was counted and the percent mortality was calculated.

In this test, for example, compounds No. 1, 2, 3, 4, 5, 6, 8, 9, 10, 11, 13, 14, 15, 16, 17, 19, 20, 22, 27, 31, 32, 33, 34, 35, 36, 39, 65, 66, 75, 76, 105, 164, 290, 304, 336, 340, 396, 409, 431, 444, 453, 518, 556, 612, 623, 624, 705, 706, 755, 762, 813, 827 and 831 at a concentration of 8 ppm active ingredient 100% mortality.

In contrast, the comparative means have the following efficiency:

Al has a mortality rate of 65% at a concentration of 40 ppm of active ingredient,

A-2 has a mortality of 40% at a concentration of 200 ppm active ingredient and 0% mortality at a concentration of 40 ppm active ingredient,

A-3 shows 0% mortality at 200 ppm active ingredient,

A-4 shows a mortality rate of 30% at a concentration of 200 ppm active ingredient.

Example 44

Test for Nilaparvala lugens, Sogatella furcifera and Laodelphax striatellus

The drug preparation diluted with water to a predetermined concentration is applied as in Example 43 by spraying on rice plants of about 10 cm high, which grow in pots with a diameter of 12 cm. The active preparation is applied in an amount of 10 ml / pot. The spraying layer is allowed to dry and each pot is covered with a protective wire mesh in the form of a cylinder 7 cm in diameter and 14 cm high. 30 female imago Nilaparvata lugens (Stal) strains that are resistant to organic phosphorus compounds are then placed inside. The pots were then kept in a constant temperature room and after 2 days the number of killed insects was determined. The percent mortality is then calculated from this number.

In the same manner as described above, the percent mortality is calculated for Sogatella furcifera (Horvath) and Laodelphax striatellus (Fallen), a strain that is resistant to organic phosphorus compounds.

and

In this test, for example, compounds No. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 29, 35, 37, 39, 43, 65, 70, 75, 79, 146, 164, 230, 303, 308, 350, 396, 409, 424, 453, 518, 529, 550, 556, 579, 612, 623, 624, 649, 701, 705, 706, 755, 758, 648 at an active compound concentration of 40 ppm 100% mortality (against all three pests tested).

In contrast, the comparative means have the following efficiency:

Al exhibits a mortality rate of 40 ppm at 50 ppm of Nilaparvata lugens, a mortality rate of 40% at Sogatella furcifera and Laodelphax striastellus,

A-2 exhibits 30% mortality against Nilaparvata lugens, 20% mortality against Laodelphax striatellus and 50% mortality against Sogatella furcifera at an active substance concentration of 200 ppm, and 0% mortality against all three pests tested at a concentration of 40 ppm active substance,

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A-3 exhibits a 0% mortality at all three species of pests tested at a concentration of 200 ppm active ingredient;

A-4 exhibits 100% mortality to Nilaparvata lugens, 0% mortality to Laodelphax striatellus and Sogatella furcifera at 200 ppm active ingredient.

Example -45

Test for peach aphids (Myzus persicae) (strain resistant to organic phosphorus compounds and carbamates)

Using peach aphids (Myzus persicae) resistant to organic phosphorus compounds and carbamates, the eggplants of about 20 cm in height are grown, which are grown in 15 cm diameter potted pots (about 200 aphids per seedling). After 1 day after contamination, the plants are sprayed with a dilute active preparation of each of the test compounds at a predetermined concentration in sufficient quantity with a sprayer. After spraying, the pots were placed in a greenhouse and kept at 28 ° C. 24 hours after spraying, the number of killed aphids was counted and the percent mortality was calculated. The test is repeated twice for each compound. ·

In this test, for example, compounds No. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 27, 29, 31, 32, 33, 35, 71, 74, 75, 98, 105, 164, 230, 231, 396, 409, 518, 529, 550, 556, 579, 612, 623, 624, 649, 705, 706, 755, 756, 758, 763, 831, 100% mortality at a concentration of 200 ppm active ingredient.

In contrast, the comparative compounds exhibit the following activity:

Arl has a mortality rate of 80% at an active substance concentration of 1000 ppm and a mortality rate of 30% at an active substance concentration of 200 ppm,

A-3 exhibits a mortality rate of 60% at 1,000 ppm and 0% at 200 ppm, and

A-4 exhibits 60% mortality at 1000 ppm drug concentration and 0% mortality at 200 ppm drug concentration.

Examples 43, 44 and 45 above are typical examples illustrating insecticidal activity and are also exemplary examples of the test compound of the invention. In the present case, however, these are only examples and the scope of the invention is not limited in any way by these examples.