Substituted sulfonyl aminomethyl benzoic acid (derivatives) and method for the production thereof

Substituted derivatives of sulfonyl aminomethyl benzoic acid and their preparation method

Full description

Background of the invention

The invention relates to the technical field of intermediate materials for the preparation of active substances, in particular sulfonylureas compounds that are effective in killing weeds.

It is known that aromatic amines can be reacted to give derivatives of sulfonic acid such as sulfochlorides and also to give sulfonamides, which, in turn, can be used in the preparation of sulfonylureas that are effective in killing weeds (574418 - Meerwein et al., Chem Berichte 90,841 - 852 (1957). ) and EP-A. There is anthranilic acid, which is known from the Journal of Pharmaceutical Chemistry, published in 1986, Part 29, No. 4, page 585, as an intermediate material for preparing certain anhydrates that are suitable for removing the activity of trypsin-like enzymes.

General description of the invention

The goal of the invention is to provide new chemical compounds that are suitable for preparing sulfonylureas that are effective in eliminating weeds. Surprisingly, this goal is achieved by compounds of formula (I):

<img file="SA1528B1_D0001.tif" />

And with it

R1 is H, or C1-C8 alkyl, C3-C8 alkenyl, or C3-C8 alkynyl, where at least the last three radicals are unsubstituted or substituted, for example by one or more radicals. Radicals selected from the group consisting of a halogen, C1 - C4 alkoxy, C1 - C4 alkylthio, carbonyl (C1 - C4) or alkyl. carbonyl [(C1-C4) alkoxy]

R2 and R3 are independent of each other and are H or acyl, preferably H.

And R4 and R5 are H

R6 is an H or C1 - C8 (alkyl) which is unsubstituted or substituted, for example by one or more radicals selected from the group consisting of a halogen, or C1 - C4 (alkoxy), or C1 - C4 (alkylthio). ; Or C1-C4) alkylsulfinyl), or C1-C4) alkylsulfonyl), or [carbonyl [(C1-C4) alkyl or CN, preferably H. R7 is a C1-C8 alkyl, C3-C8 alkenyl, or C3-C8 alkynyl which is either unsubstituted or substituted, for example by one or more radicals selected from the halogen group, or Cl - C4) alkoxy) or Cl - C4) alkylthio),

or R7 is an aryl (C6-C14) (e.g. phenyl) which is unsubstituted or substituted, e.g. with one or more moieties of the halogen, N52, CN, or C1-C4 alkyl group, or Cl - C4 (haloalkyl), or Cl - C4 (alkoxy)' or R7 form mono - or Cl - C8 (alkylamino - di) which is unsubstituted or substituted, for example by one or more moieties of the halogen group, or Cl - ) alkoxy C4), or C1-C4 (alkylthio), or Cl - C4) alkylsulfinyl)' or Cl - ) alkylsulfonyl C4), Or [C1-C4) alkyl)[ carbonyl, or [carbonyl [(C1-C4) alkoxy, or CN. Or R6 and R7 together form a chain with the formula -1 CH2)m Bm) — which is unsubstituted or substituted, for example by one or more Cl - C4 (alkyl radicals), where m = 2, 3, or 4, and m1 = zero or 1, and CO = B or SO2. And the R8 moieties can be the same or different and are Cl - C4 alkyl, Cl - C4 alkoxy, carbonyl [(C1-C4) alkyl, or carbonyl [(C1-C4) alkoxy, which are unsubstituted or substituted. For example, by cleaving one or more radicals selected from the group consisting of a halogen, a C1-C4 alkoxy, a Cl-C4 alkylthio, or a carbonyl [(C1-C4) alkyl] or [(C1-C4) Alkoxy]carbonyl, or R8 is a halogen or NH2.

And n can be 0, 1, 2, or 3, preferably zero. The preferred compounds that have the formula (I) are those with:

R1 is H or C1-C4 (alkyl), preferably C1-C4 (alkyl). And R2 and R3 are H. And r4 and R5 are H.

And R6 is H.

And R7 is C1-C4 alkyl.

And n is zero.

The compounds of formula (I), which are of special importance, are those in which the group CR4R5 - NR6 - SO2 - R7 is in the para position with respect to the group CO-OR1 -. If they are R6 and R7 together, they form a series of the formula. (CH2)m Bm1 - and m1 = 1, it is preferable for B to attach to the nitrogen atom to which R6 is attached. Examples of compounds of formula (I) are listed in the following Table 1:

<img file="SA1528B1_D0002.tif" />

<img file="SA1528B1_D0003.tif" />

<img file="SA1528B1_D0004.tif" />

In Table 1, methyl = Me, ethyl = Et, n-propyl = nPr, isopropyl = iPr, n-butyl = nBu, and phenyl = Phe.

If the expression acyl is used in the present description, it denotes a form of an organic acid that is originally obtained by deleting the OH group from the organic acid, for example the carboxylic acid moiety and the radioactive acid moieties thereof, such as thiocarboxylic acids, and optionally iminocarboxylic acids. N-substituted carbonic monoesters, and optionally N-substituted carbamic acids, sulfonic acids, sulfinic acids, phosphonic acids, and... phosphinic acids

Preferably, any acyl radical should be a formyl or an acyl from the group consisting of CO - Rx. or cs - Rx, or CO- ORx, or CS - ORx, or cs - SRx, or CRx - NRy, or SORy, or SO2Ry, where both Rx and Ry are a hydrocarbon moiety - Cl- C10 such as Cl - C10 alkyl or aryl - C6 - C10, each unsubstituted or substituted, for example with one or more substituents selected from the group consisting of a halogen such as F, Cl, Bn or I, an alkoxy, haloalkoxy or hydroxyl, or amino, cyano, nitro, or alkylthio; Or the acyl is carbonyl amino, or aminosulfonyl, and the two parts mentioned are Finally, they are unsubstituted, or have one substitution at N, or two substituents at N, N, for example with substituents from the alkyl or aryl group. The acyl is, for example, formyl or haloalkylcarbonyl, or an alkylcarbonyl as (C1-C4)

alkylcarbonyl, or carbonyl phenyl, and the phenyl ring can be substituted, or alkyloxycarbonyl, such as Cl - C4 (alkyloxycarbonyl) or phenyloxycarbonyl, or

benzyloxycarbonyl, or alkylsulfonyl, such as Cl-C4 (alkylsulfonyl), alkylsulfinyl such as alkylsulfinyl (C1-C4), and N-alkyl-l-iminoalkyl, such as: N-(C1-C4)-l-imino-(C1-C4) alkyl, radicals, and organic acids

The other.

In formula (I) and the general formulas used hereinafter, we can be alkyl, alkoxy, haloalkoxy, haloalkyl, and alkylthio radicals, and the corresponding substituted radicals, in each case a straight or branched chain, i.e. the carbon skeleton. Unless otherwise specified, low carbon structures, for example those with 1 to 4 carbon atoms, are preferred among radicals. Alkyl moieties, i.e. also structural connotations such as haloalkyl, alkoxy, and the like, are, for example, methyl, ethyl, n- or i-propyl, n-or i-, t-or 2-butyl, and compounds pentyls, hexyls such as n-hexyl, i-hexyl, and l,3-dimethylbutyl, heptyls such as n-heptyls, l-methylhexyl, and l,4-dimethylpentyl, and alkenyl and alkynyl radicals that have the meaning of non-radicals. Possible saturated molecules that correspond to alkyl radicals, for example an alkyl is an allyl, and

1-methylprop-2-en-1- yl, 2-methylprop-2-en-l-yl, but-2-en-l-yl, but-3-en-l-yl, 1-

methylbut-3-en-1-yl and l-methylbut-2-en-l-yl; alkynyl

The alkynyl is, for example, -1,propargyl, but-2-yn-1-ylbut-3-yn-l-yl, 1-

methylbut-3-yn-l-yl.

And alkenyl, which is, for example, any form (C3 - C8) alkenyl) &amp;, it is preferable that the alkenyl radical has from 3 to 8 carbon atoms and in which the double bond is not located at the carbon atom linked to the remaining part of the compound (I) (position &amp;yl&amp;). This also applies in a similar way to alkynyl moieties.

The halogen is, for example, fluorine, chlorine, bromine, or iodine. And haloalkyl and haloalkenyl and haloalkenyl are alkyl, or alkenyl; or alkynyl, each of which is partially or completely substituted for a halogen, preferably with fluorine, chlorine and/or bromine, and particularly with fluorine or chlorine, for example CF3, CHF2, CH2F, CF3CF2, CH2FCHCl2, And CCl3, and CHCl2, and CH2CH2Cl, and the haloalkoxy is, for example, OCF3, and OCHF2, and OCH2F, and CF3CF2O, and OCH2CF3, and OCH2CH2Cl, and this also applies. Likewise on haloalkenyloxy moieties and other substituted halogen moieties.

Substituted radicals such as substituted hydrocarbon radicals, for example, alkyl, alkenyl, alkynyl, and substituted aryl radicals, for example, phenyl, are, for example, a substituted radical which is derived from the unsubstituted structure, and substituents are, for example, a radical One or more, preferably 1, 2, or 3, radicals selected from the group consisting of haloalkoxy, alkoxy, halogen, hydroxyl, alkylthio, nitro, amino, carboxyl, cyano, azido, and alkoxycarbonyl, and alkylcarbonyl, formyl, carbamoyl, carbonyl alkylamino, di-mono, and substituted amino such as amino acyl, mono-di alkylamino, alkylsulfmyl, and

haloalkylsulflnyl and alkylsulfonyl, and haloalkylsulfonyl, and in the case of cyclic radicals also alkyl and haloalkyl, and unsaturated aliphatic radicals which correspond to the saturated radicals containing the aforementioned hydrocarbon, such as alkenyl, alkenyloxy, alkynyl, alkynyloxy and the like. In the case of cracks, radicals with atoms

Carbon, preferably those with 1 to 4 carbon atoms, especially 1 to 2 carbon atoms.

As a rule, substituents selected from the group consisting of halogen are preferred, for example fluorine and chlorine, Cl - C4) alkyl, preferably methyl or ethyl, haloalkyl (C1 - C4), preferably trifluoromethyl and methyl, C1 - C4) alkoxy. ), preferably methoxy or ethoxy, nitro, (C1-C4) haloalkoxy and cyano. Particularly preferred substituents in this context are methoxy, methyl, and. chlorine and optionally preferably phenyl or phenoxy. The substituted is phenyl or phenoxy, each of which is unsubstituted or has one or several substitutions, preferably up to three substitutions, with identical or different radicals selected from the group consisting of halogen, and (C1 - C4) alkyl. And C1-C4) alkoxy), C1-C4) haloalkyl, C1-C4) haloalkoxy and nitro, for example 0-, m- and p-tolyl, and the compounds dimethylphenyls, 2-, 3-, and 4-chlorophenyl and phenyl, and 2-, 3-, and 4-trifluoro and trichlorophenyl, and , 2,4-, and 3-,2-5, 5-, 2,3-dichlorophenyl, and 0-, m- and p-methoxyphenyl. If the substituents are distinguished by one or more radicals from among the group of radicals, this suffices for both the substitution with one or more identical radicals and the single substitution or Multiple with different cracks.

The subject matter of the invention is also all the solids included in formula (I) and their mixtures. These compounds of formula (I) contain one or more asymmetric carbon atoms that are not shown separately in formula (I). Possible enantiomers distinguished by their distinct stereoisomers, such as enantiomers or dimers, are all contained in formula (I) and can be obtained from mixtures of enantiomers in familiar ways or otherwise through stereoselective reactions in combination with the use of starting materials consisting of a single enantiomer. Formula (I) also includes the aforementioned atomistic compounds, to the extent that they are formed by proton transfer and are chemically stable. Compounds of formula (I) may be salts with an acidic hydrogen atom replaced by a suitable cation. These salts are, for example, mineral salts, preferably salts of alkali metals or salts of alkali earth metals, especially sodium salts and potassium salts, or other ammonium salts or organic amines. Likewise, salt formation can occur when an acid reacts additionally with basic groups, such as amino. Suitable acids used for this purpose are strong inorganic and organic acids, for example, HCl, Hr, H2SO4, HNO3, or formic acid.

Formula (I) compounds are successfully synthesized with very high products and purity levels, starting with the formula (II) compounds mentioned here later.

The object of the present invention is therefore a process for preparing formula (I) compounds that includes the following steps:

(1a) Reaction of the compound of formula (II):

<img file="SA1528B1_D0005.tif" />

By catalytic hydrogenation in the absence of acid to give the compound of formula (III) or by catalytic hydrogenation in the presence of acid, eg -H+X, where Br, or -1, or 0 HSO4, and -2 1/2SO4, and -H2PO4, and -1/2HPO42, and -1/3PO43, or OCOR- (where R = H or C1 - C8) alkyl) to be given Compound of the formula (Illa), where - And - 1/2HPO42, and 1/3 PO43- or OCOR - (where H = R or alkyl).(Cl-C8)

<img file="SA1528B1_D0006.tif" />

<img file="SA1528B1_D0007.tif" />

This is followed by:

(1b) The reaction of the compound of formula (III) and (IIIa) with a derivative of sulfonic acid to give the compound of formula (I), where r2, r3, and H = R6,

or

(2a) 1-The reaction of the compound of formula (II)

<img file="SA1528B1_D0008.tif" />

By familiar reduction methods for nitro compounds to give the compound of the formula (IV)

<img file="SA1528B1_D0009.tif" />

This follows

2- The reaction of the compound of formula (IV) either by catalytic hydrogenation or by familiar reduction methods for nitrites to give the compound of formula (III) or (IIia). This is followed by:

(2b) The reaction of the compound of formula (III) or (IIIa) with the sulfonic acid derivative to give the compound of formula (I), where R2, R3, and H = R6, or

(3a) 1- Reaction of the compound of formula (II)

<img file="SA1528B1_D0010.tif" />

By familiar reduction methods for nitrites to give a compound of the formula (V) or (Va), where (-)X is as defined by the formula (IIIa).

<img file="SA1528B1_D0011.tif" />

<img file="SA1528B1_D0012.tif" />

This is followed by:

2- Reacting the compound of the formula (V) or (Va) with reduction methods familiar to nitro compounds or by catalytic hydrogenation to give the compound of the formula (III) or (IIIa). This is followed by:

(3b) The reaction of the compound of formula (III) or (IIIa) with a derivative of sulfonic acid to give the compound of formula (I), where R2, R3, and H = R6, or

(4a) 1-The reaction of the compound of formula (II)

<img file="SA1528B1_D0013.tif" />

By known reduction methods for nitrites to give a compound of the formula (V) or (Va), where -X is as defined in formula (IIIa)

<img file="SA1528B1_D0014.tif" />

<img file="SA1528B1_D0015.tif" />

2 This is followed by the reaction of the compound of the formula (V) or (Va) with a derivative of sulfonic acid to give the compound of the formula (VI).

<img file="SA1528B1_D0016.tif" />

This is followed by:

(4b) The reaction of the compound of formula (VI) by reduction methods familiar to nitro compounds or by cataljdic hydrogenation to give the compound of formula (I), where r2, R3, and R6 = H.

The compounds of formulas (III), (IIIa), (V), (Va), and (VI) are new and are also the subject of the present invention.

Compounds of formula (I) where R2 and/or acyl = R3 can be obtained by acylating (inserting an acyl group). Compounds of formula (I) where r2 and H = r3 can be obtained with acylating agents such as sulfonyl halides, carbonyl halides, and carbamoyl halides. ; carboxylic anhydrides, sulfonic anhydrides, haloformic esters or isocyanates by customary methods (see, for example,

L.-F. Tietze. Th. Eicher Reaktionen and Synthesis in Organisch - Chemischen Praktikum [Reactions and syntheses in the Organochemical Laboratory Practical] , Thieme Verlag Stuttgart/New York, 1981, pp.131,316,318,345; RC Larock,

979,981.. Comprehensive Organic Transformations (1989), pp. Examples of suitable solvents are non-proton donor solvents such as dichloromethane, or acetonitrile; Or dioxane, or tetrahydrofuran, or toluene and chlorobenzene, preferably at temperatures from 0 C to the boiling point of the solvent.

Compounds of formula (I) where C1 - C8 alkyl = R6 unsubstituted or substituted can be obtained, for example for alkylating compounds of formula (I) where H = R6 with alkylating agents such as alkyl halides, and alkyl sulfates such as dimethyl sulfate or alkyl tosylates by methods The familiar. Examples of suitable solvents are acetone and

dimethylformamide

(cf., for example, R. C. Larock, Comprehensive Organic Transformation (1989), p. 398; L.-F. Tiettze, Th. Eicher, Reaktionen and Synthesen in organisch-chemischen Praktikum, Thieme Verlag Stuttgart / New York, 1981, P.75;

1981 (Chemistry) VEB, Berlin

Alkylating can be done in the presence of bases such as K2CO3, NaH, or alkoxides such as sodium alkoxide. It is preferable that the starting material be compounds of formula (I) in which R2 and R3 are acyl.

Compounds of the formula (I) can also be obtained where R6 = Cl - C8 alkyl unsubstituted, or substituted, for example by reductive amination, for example by aldehydes and ketones in the presence of reducing agents such as H2/catalyst, or formic acid, Or zinc/HCl, or sodium borohydride, or sodium cyanoborohydride. An example is the Leuckard–Wallach reaction using formaldehyde. formic acid. The preferred processes are those in which the nitro and nitrile group in compounds of formula (II) are reduced together in a one-step process by catalytic hydrogenation according to the process variable (1a) to give compounds of formula (III) or (IIIa).

The amino compounds of the formula (III) and (V), which are obtained as intermediates in the process according to the invention, can also appear in the form of their salts (IIIa) and (Va) and can then react when the reaction or operation occurs in the acidic medium. The symbols given in Formulas (II), (III), (IIIa), (IV), (V), (Va) and (VI) have the same meaning as in Formula (I), including the preferred variations given here. . The preferred compounds for formulas (II), (III), (IIIa), (IV), (V), (Va) and (VI) are those in which the groups form CN- (formulas (II) and (IV)), And - CH2 NR - (formulas (III) and (V)), and CH2 - NH3 + X- - (formulas (Va) and (IIIa))

And SO2 - R7 - NR6 - CH2- (formulas (VI)), in the para position with respect to the group

- CO - OR1

Furthermore, the sub-steps of the process according to the invention are also the subject of the invention. Compounds of formula (II) are known, compare, for example, German Patent No. C3 39799 22 or Journal of the American Chemical Society No. 99, 6721 (1977). The catalytic hydrogenation of the compound of formula (II) with the process variant (1a), or of the compound of formula (IV) with the process variant (2a2), or of the compound of formula (V) or (Va) with the process variant (3a2), or of the compound of formula (VI) is successfully accomplished. With the process variable (4b) using familiar hydrogenation methods. Examples of hydrogen sources that can be used are hydrogen gas, hydrazine, or NH = NH. Particularly suitable hydrogenation catalysts are noble metal catalysts, for example, Pd, Pt, Rh, Ir, Ni, or Co catalysts.

Noble metals can be used in elemental form or as oxides or halides. Noble-metal catalysts can be used as needed without or, preferably, with carrier materials such as active charcoal, diatomaceous earth, or

silicates.

Hydrogenation can be carried out at atmospheric pressure and using hydrogen pressure above atmospheric pressure, as a rule between 1 and 100 bar, preferably from 1 to 0.5 bar. In general, the appropriate temperature is in the range from -20 to 0.51°C, preferably between 0 and 120°C. Examples of solvents suitable for hydrogenation are solvents from groups such as water, and alcohols such as methanol or ethanol; and ethers such as diethyl ether, tetrahydrofuran, or dioxane, amides such as dimethylformamide or dimethylformamide, esters such as ethyl acetate, organic carboxylic acids such as formic acid, or acetic acid, and aromatic hydrocarbons such as toluene, xylene, chlorobenzene, or Halogenated aliphatic hydrocarbons, such as CH2CI2, and it is possible to use solvents in pure form or as mixtures.

It is preferable to carry out the catalytic hydrogenation of compounds of formula (II) with the process variant (1a) or for compounds of formula (IV) with the process variant (2a2) in the presence of 1-10 molar equivalent of acid. The preferred solvents to use are alcohols such as methanol or ethanol, or water. Examples of suitable acids are inorganic acids or carboxylic acids. The preferred ones are acids with the formula - H + X, where - X is the equivalent of the acid radical, such as halogen, for example.

Example - Cl, or -Br' or -1,or -4 HSO, or -2 1/2SO4, or -H2PO4, or 1/2 -HPO42, or -1/3PO43, or OCOR (where H = R or Cl - c8) alkyl), for example hydrohalic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, or acetic acid. If, for example, the last two acids mentioned are used, the acids may completely act as a solvent. Catalytic hydrogenation of formula (IV) compounds can also be carried out using 1-10 molar equivalents of ammonia, nickel, or cobalt catalysts, such as Raney nickel or Raney cobalt, which is preferred. The preferred solvents to use in this context are alcohols such as methanol or... ethanol

The reduction of the nitro group can be carried out in compounds of formula (II) by means of the process variable (2a1), or compounds of formulas (V) and (Va) by means of the process variable (3a2), or compounds of formula (VI) by means of the process variable (4b) with reduction agents. Familiar with aromatic nitro compounds. These reducing agents and reaction conditions are described, for example, in the comprehensive organic transformations of R. c. Larock, (1989), pp. 1 1 4 - 5 1 4, VC H Publishers and the articles cited here. Examples of preferred reducing agents are Fe, Zn, Sn or their salts such as FeSO4 or Sn-II salts such as SnCl2. Examples of suitable solvents are organic carboxylic acids, alcohols and/or mineral acids. In general, the reaction temperature is between 0 C and the boiling point of the solvent.

The reaction of the nitrile group can be carried out in compounds of formula (IV) by means of the process variable (2a2) and compounds of formula (II) by means of process variables (3a1) and (4a1) using reducing agents familiar to nitrites. These reducing agents and reaction conditions are described, for example, in R. C. Larock's Comprehensive Organic Transformation, (1989) pp. 437-438, VCH Publishers Inc. and the articles cited here. Examples of preferred reducing agents are boron hydride compounds or aluminum hydride compounds such as BH3 / THF, BH2 / DMS and their salts such as NaBH4. Examples of suitable solvents are ethers such as dioxane or tetrahydrofuran. The reaction temperature is generally between 0 C and the boiling point of the solvent. If the reaction product is then run in an acidic medium, for example methanol/HCl, the compound of formula (III) (process variant 2a2) or the compound of formula (V) (process variants 3a1 and 4a1) can be obtained in the form of a salt of formula (IIIa). ) or ( Va ), respectively, which can then react in a corresponding manner to compound ( III ) or compound ( V ), respectively. Acylating agents can be carried out: compounds of formula (III) or (IIIa) by the process variable (1b), (2b), or (3b) or compounds of formula (V) or (Va) by the process variable.

(4A2) using a sulfonic acid suspension, under conditions familiar to acylation reactions, to give compounds of formula (VI) in the case of compounds of formula (V) or (Va), or to give compounds of formula (I) according to the invention in the case of compounds of formula (III) or ( IIIa). For example, compounds of formula (III), (IIIa), (V) or (Va) are reacted in appropriate solvents with sulfonic acid moieties in the presence of bases as acid acceptors to give compounds of formula (I) or (VI), respectively. Examples of solvents suitable for acylation processes are:

Solvents of groups such as water, alcohols such as methanol or ethanol, halogenated aliphatic hydrocarbons such as CH2CI2, aromatic hydrocarbons such as toluene', chlorobenzene, or xylene, others such as diethyl ether, tetrahydrofuran, or dioxane, and ketones such as acetone or isobutyl ketone esters such as ethyl acetate, and non-proton donor solvents such as acetonitrile or dimethylformamide; Or dimethylformamide, and it is possible to use the solvents in pure form, or as mixtures. Preferable is water and mixtures of water and water-soluble organic solvents from the groups mentioned above.

Suitable bases are inorganic and organic bases, for example carbonates such as K2CO3, Na2CO3, or NaHCO3, alkaline metal hydroxides, alkaline earth metal hydroxides such as NaOH, KOH, 2(Ca(OH), or amines. Such as triethylamine. In general, bases are used in quantities of 1-01 molar equivalent, and preferably 1-5 molar equivalent, for each compound of formula (III) or (V), and when using compounds of formula (IIIa) or (Va), the smallest amount of the base It is used to be at least 2 molar equivalent.

Examples of suitable sulfonic acid derivatives are sulfonyl halides, fluorides, chlorides, bromides, iodides, and sulfonic anhydrides. Preferred are sulfonic acid derivatives with the formula R7 - SO2 - Z where R7 is defined as the formula (I), and Z is a leaving group such as a halogen (for example, fluorine, chlorine, bromine, or iodine) or O - SO2 - Rz, where Rz is defined with respect to R7 in formula (I).

For example, acylation is carried out in such a way that compounds of the formula (Ill), (IIIa), (V), or (Va) react with sulfonic acid derivatives in suitable solvents in the presence of a suitable base, generally at temperatures ranging from -0 To 100 m. The preferred temperatures are from -10 to 50 C. The amounts of sulfonic acid derivatives are generally 1-01 molar equivalent, and preferably 1-5 molar equivalent, for each compound of formula (III), (IIIa), (V), or (Va).

In addition to the compounds of formula (I) and their preparation, the present invention also relates to their subsequent reaction to give the compounds of formula (VII) and (VIII). Perhaps, compounds of formula (I) where r2 and/or acyl = R3 must first be converted in familiar ways to compounds of formula (I)

Where H = R3 = R2, then react on these compounds after that to give the compounds of formulas (VII) and (VIII). The symbols used in formulas (VII) and (VIII) have the same meanings as they were mentioned for formula (I), including The preferred ranges mentioned here, and Y in formula VII) are a halogen such as fluorine, chlorine, bromine, or iodine. The preferred compounds for formulas (VII) and (VIII) are those in which the group CH2 - NR6 - SO2 - R7 is in the position next to the group CO - OR1.

<img file="SA1528B1_D0017.tif" />

As described in (European Patent No. 534,723-A), the compounds of formulas (VII) and (VIII) are suitable product materials for the preparation of sulfonylureas active in weedicides, and the preparation of the compounds of formulas (VII) and (VIII) is particularly effective. In the current process according to the invention, compounds of formulas (VII) and (VIII) can be obtained with very good products and high degrees of purity.

The methods for converting (6) anilines into sulfonyl halides are known (see, for example, Chem. Berichte Part 90, pages 481-592 (1957) by the inventor H. Meerwein and others). Surprisingly, compounds of formula (I) where R2 and H = R3 react successfully to give compounds of formula (VII) based on the procedures described in Ref. Thus, compounds of formula (I) where r2 and H = r3 can be diazo grouped under appropriate conditions and then coupled with suitable SO2 sources, such as SO2 gas, Na2S2O5, or NaHSO3 in the presence of acids such as carboxylic acids, on eg acetic acid, or inorganic acids, eg HY hydrohalic acids such as HCl or

Hr, and catalysts, for example copper catalysts based on Cu(I) and/or Cu(II) salts to give sulfonyl halides of the formula (VII).

The diazotization group can be introduced by suitable diazotizing agents such as NaNO2 in the presence of acids such as inorganic acids, preferably HY hydrohalic acids, such as HCl or HBr. The solvent used should preferably be a water/acid mixture, especially a mixture of water/carboxylic acid (eg acetic acid) or water/mineral acid (eg HY hydrohalic acid such as HCl or HBr). In general, the reaction temperature ranges from -20 to 50 C, and preferably from -10 to 0 C. The following are examples that can be used as solvents for the following coupling reaction: water, carboxylic acids such as acetic acid, carboxylic esters such as ethyl acetate, ethers such as diethyl ether, tetrahydrofuran, or dioxane, halogenated aliphatic hydrocarbons such as CH2CI2 or dichloroethane, and aromatic acids. Hydrocarbons such as toluene, chlorobenzene, or xylene, or ketones such as acetone or methyl isobutyl ketone. Furthermore, the reaction mixture contains acids, for example carboxylic acids such as acetic acid or mineral acids such as HY hydrohalic acids, for example HCl or HBr, which are still present from the double nitration reaction and/or added when the coupling reaction is carried out. . Examples of SO2 sources that can be used are, for example, SO2 gas (1-10 equiv), Na2S2O5 (1-10 equiv), or NaHSO3 (1-10 equiv), in the presence of catalysts, for example copper catalysts Such as CuCl (10 - 20% mol), or CuCl2 (1 - 02% mol), or CuBr (1 - 02% mol), or CuBr2 (1 - 02% mol).

Starting from sulfonyl halides of formula (VII), the aminolysis (7), which produces sulfonic amides of formula (VIII), is carried out, surprisingly, successfully with high efficiency and high yields by reacting the products of formula (VII), for example, in suitable solvents with... ammonia Aminolysis can be carried out with suitable reactants, for example 2-10 M equivalent of an aqueous ammonia solution or NH3 gas in the presence of a solvent, for example ketones such as acetone or methyl isobutyl ketone, halogenated aliphatic hydrocarbons such as CH2CI2, and aromatic hydrocarbons such as xylene. , or toluene, or chlorobenzene 4 and ethers such as diethyl ether, or tetrahydrofuran, or dioxane, and esters such as ethyl acetate, and non-proton-donating solvents such as dimethylformamide, or dimethylformamide or acetonitrile, or mixtures of these solvents. In general, the reaction temperature is from -10°C to 100°C, preferably from -10°C to 40°C, and particularly from -10°C to

20 pm.

Compounds of formulas (VII) and (VIII) can then be reacted in different ways to give sulfonylureas, preferably sulfonylureas with formula (XIII) and/or their salts, for example by:

(8) The reaction of the sulfonyl halide of formula (VII) with the cyanate MOCN, in which M is an ammonium ion or an alkali metal ion such as Li, Na, or K, and with an amino heterocycle of formula (XII) in the presence of a base. To give a compound, sulfonylureas

or

<img file="SA1528B1_D0018.tif" />

(9) The reaction of the compound of formula (VIII) with a heterocyclic carbamate of formula (IX), at which the pH is unsubstituted or substituted phenyl to give the compound sulfonylureas,

or

<img file="SA1528B1_D0019.tif" />

(0 1) (a) First, the reaction of a heterocyclic amino of the formula (XII) in the presence of a base such as, for example, triethylamine, with phosgene to give a heterocyclyl isocyanate group of the formula (X), and (b) the reaction of the heterocyclic isocyanate The heterocyclyl isocyanate formed, of formula (X), is combined with phenylsulfonamide of formula (VIII) to give the compound sulfonylureas, or

<img file="SA1528B1_D0020.tif" />

<img file="SA1528B1_D0021.tif" />

(11) (a) The reaction of the compound of the formula (VIII) with an alkyl isocyanate, for example RNCO, with C1 - C10 alkyl = R - and with phosgene to give sulfonyl isocyanate with the formula (XI), and (b) the reaction of the sulfonyl isocyanate formed, with the formula ( XI), with a heterocyclic amino group of the formula (XII) to give a sulfonylureas compound, or

<img file="SA1528B1_D0022.tif" />

(12) (a) The reaction of the compound of the formula (VIII) with a derivative of carbonic acid such as - R - CO OPh, in which phenyl = unsubstituted or substituted Ph and halogen = R or unsubstituted or substituted phenoxy to give phenylsulfonyl carbamate with the formula (XIV), And (b) the reaction of the formed phenylsulfonyl carbamate, with the formula (XIV), in which Ph = unsubstituted or substituted phenyl, with a heterogeneous amino ring with the formula (XII) to give a compound. sulfonylureas

<img file="SA1528B1_D0023.tif" />

The symbols used in formulas IX, In addition, the following meanings are also used:

Rx and Ry, independent of one another, are hydrogen atom, halogen, C1 - alkyl C4, C1 - C4 alkoxy, or C1 - C4 alkylthio, where each of the three has moieties.

The last mentioned is unsubstituted or replaced by one or more radicals selected from the group consisting of halogen, C1-C4) alkoxy, and C1-C4) alkylthio), or is mono or amino [(C1-C4) alkyl] di, Or C2 - C6) alkenyl), or alkynyl (C2-C6), or alkenyloxy (C3 - C6), or (C3 - C6). alkynyloxy and X is CN or N.

Y is a halogen such as fluorine, or chlorine, and bromine or iodine, preferably chlorine.

The preferred compounds of the formula (XI), (XIII) and (XIV) are those in which the group CH2 - NR6 - SO2 - R7 - is in the bar position with respect to the group COOR1 -. Sulfonylureas, such as compounds of formula (XIII), can be salts in which the hydrogen group - SO2 - NH - is replaced with a cation suitable for agricultural uses. Examples of these salts are mineral salts, especially salts of alkali metals or salts of alkaline earth metals, especially sodium salts and potassium salts, or other ammonium salts, or salts with organic amines. Likewise, salt formation can be carried out by the addition reaction of an acid with basic groups, such as, for example, amino and alkylamino. Acids suitable for this purpose are strong inorganic and organic acids, for example, HC1, HBr, H2SO4, or HNO3. If the current description mentions sulfonylureas, such as compounds of formula (XIII), then this must also be understood to include their salts in each case as well.

In a variant of the process (8), the reaction of VII (sulfonyl halides) with heterogeneous amino rings of the formula (XII) and MOCN cyanates is carried out preferably by catalytic analysis of a base in inert, non-proton-donating organic solvents such as ethyl acetate, tetrahydrofuran, toluene, or acetonitrile. Between zero and the boiling point of the solvent. Examples of suitable bases are organic amine bases, especially pyridines such as pyridine or 3-methylpyridine. In a variant of the process (9), it is preferable to carry out the reaction of compounds of formulas (VIII) and (IX) with a basic catalyst in an inert organic solvent such as dichloromethane, or acetonitrile; Or dioxane, or tetrahydrofuran, or ethyl acetate between zero and the boiling point of the solvent. Examples of bases used are K2CO3 or organic amine bases, such as:

(l,8-diazabicyclo[5.4.0]undec-7-ene(DBU) In a variant of process (10), the reaction of a compound of formula (XII) with phosgene is carried out to give a heterocyclic isocyanate group of formula (X), for example In inert organic solvents such as ethyl acetate, dioxane, or aromatic solvents such as chlorobenzene, and if appropriate with the addition of an organic amine base such as triethylamine, generally between 0 C and the boiling point of the solvent. The following reaction between the compound of formula (X) with the compound of formula (XIII) is carried out, for example, in inert solvents such as ethyl acetate, dioxane, or aromatic solvents such as chlorobenzene, preferably in the presence of bases such as K2CO3 or trialkylamines such as triethylamine or tributylamine. Generally at temperatures from -20°C to the boiling point of the solvent (compare for example European Patents 232067-A and 166516-A).

In a variant of process (11), a compound of formula (VIII) is reacted with alkyl isocyanate phosgene to give phenylsulfonyl isocyanates of formula (XI), for example in inert solvents such as dichloromethane, acetonitrile, dioxane, tetrahydrofuran, toluene, or chlorobenzene. In general, at temperatures between 20°C and the boiling point of the solvent. The following reaction of a compound of formula (XI) and heterocyclic amino groups of formula (XII) is carried out, for example, in inert solvents such as dichloromethane, acetonitrile, dioxane, tetrahydrofuran, toluene, or chlorobenzene, generally at temperatures from 0 to Boiling point of the solvent (compare, for example, US Patent No. 4,481, 029).

In the process variant (12), the reaction of the compound of formula (VIII) is carried out with a derivative of carbonic acid, for example phenyl di carbonate, or phenyl chloroformate, to give phenylsulfonyl carbamate of formula (XIV), for example in inert solvents such as xylene, or dichloromethane, or acetonitrile; or dioxane, or tetrahydrofuran, or toluene, or chlorobenzene, preferably in the presence of dilute base K2CO3 or organic amine bases such as triethylamine, preferably at temperatures from 20°C to the boiling point of the solvent (compare, e.g. US Patent Nos. 4,684,393 and 4,743,290). The subsequent reaction of the compound of formula (XIV) with the amino heterocycles of formula (XII) is carried out, for example, in inert solvents such as xylene, dichloromethane, acetonitrile, dioxane, tetrahydrofirran, or toluene; or chlorobenzene, generally at temperatures between 20°C and the boiling point of the solvent.

Thus, the compounds of Formula (I) according to the invention enable the effective preparation of herbicidal sulfonylureas and other active substances.

Detailed description

Examples: Example 1:

A) 3-Amino-4-methoxycarbonylbenzylammonium chloride: After adding 365 ml of concentrated hydrochloric acid (4.37 mol) and 9 g of PtO2, a suspension of 900 g (4.37 mol) of methyl 4- is first hydrogenated. cyano-2-nitrobenzoate in 13.5 liters of methanol at room temperature at a hydrogen pressure of 1 bar. After hydrogen absorption decreases, the pressure is increased to 17 bar, and hydrogenation continues until hydrogen absorption is complete. To advance the process, the atmospheric pressure is reduced, the catalyst is removed by filtration through silica gel and the filtrate is completely concentrated under vacuum. The remainder is extracted from digestion by:

Ethyl acetate yields 3-amino-4-methoxycarbonylbenzylammonium chloride, yielding 757 g (80%), and melting point 185 - 190 C (decomposition). B) Methyl 2-amino-4-methanesulfonylaminomethylbenzoate:

3 g of 3-amino4-methoxycarbonylbenzylammonium chloride (1.8 mmol) is dissolved in 5.0 ml of dimethylformamide, and triethylamine (2.8 g, 27.7 mmol) is added, and the mixture is then reacted to zero. - 10 M with a solution of methanesulfony chloride (1.6 g, 13.8 mmol) in 20 ml of

dimethylformamide. After an hour, the solvent is removed under vacuum and the remainder is extracted by water/dichloromethane extraction. The collected organic extracts are washed with water, dried (Na2SO4), and then evaporated in a rotary evaporator. The remainder obtained from water is crystallized, whereby 3 g (4 8%) of: methyl 2-amino4-methanesulfonylaminomethylbenzoate is obtained with a melting point of 120 - 121 C. C): Methyl 2-chlorosulfonyl-4-methanesulfonylaminomethylbenzoate After adding 5 ml of ice acetic acid, a solution of 3 g (1.1 6 mmol) methyl 2-amino-4-methanesulfonylaminomethylbenzoate in 2 0 ml of hydrochloric acid is treated. concentrated acid at 0-5°C over a period of 0.5 hours with an aqueous NaNO2 solution (81,. g, 1.7 1 mmol, 10 ml of water), and stirring continues for 5.0 hours at 5 °C. In parallel, 34.0 g (3.5 mmol) of CuCl are suspended in 30 ml of Glacial acetic acid is pre-saturated with SO2 gas, and the mixture is then treated with 0.3 ml of toluene. The previously prepared diazonium salt solution is added drop by drop to this mixture at 35°C over a period of 0.5 hours, with the spontaneous gas emission starting. After an hour, the mixture is treated with water, the phases are separated, and the aqueous dichloromethane phase is extracted again.

The collected organic phases are washed, dried (Na2SO4) and concentrated under vacuum. Extracting the remainder by stirring with toluene produces a product of 2.5 grams (63%) of Methyl 2-chlorosulfonyl-4-methanesulfonylaminomethylbenzoate with a melting point of 93-94 C. D): Methyl 2-sulfamoyl-4-methanesulfonylaminomethylbenzoate is processed as a solution of 1 1 g (32 mmol):

methyl 2-chlorosulfonyl-4-methanesulfonylaminomethylbenzoate in 0.02 ml of THF at 0 C by 1.1 g (64 mmol) of NH3 gas. To continue the process, the mixture is concentrated under vacuum. Extracting the remainder by stirring with water, then filtering and drying under vacuum gives 8.3 g (80%) of:

Methyl 2-sulfamoyl-4-methanesulfonylaminomethylbenzoate with a melting point of 85 1 - 87 1 M e)

Methyl 2-[3-(4,6-dimethoxypyrimidin-2-yl)ureidosulfonyl]-4-methanesulfonaminom

ethylbenzoate

87.15 g (2677.0 moles) are suspended from:

Methyl 2-sulfamoyl-4-methanesulfonylaminomethylbenzoate and 74.42 g (2677.0 mol) of N-(4,6-dimethoxypyrimidin-2-yl)phenylcarbamate in 0.6 ml of acetonitrile, cooled with ice at 5°C. The mixture is processed at 4.0 4 ml 9

(2677, 0 mol) l,8-diazabicyclo[5.4.0]undec-7-ene over 0.5 hours. After two hours at room temperature, approximately two-thirds of the solvent was removed under vacuum and the remainder was stirred vigorously with 0.06 ml of 2NHC1 and 400 ml of diisopropyl ether. The precipitated product is filtered by vacuum, washed successively with diisopropyl ether (twice each time) and dried under vacuum. This gives 125 grams:

methyl 2-[3-(4,6-dimethoxypyrimidin-2-yl)ureidosulfonyl]-4-methanesulfonaminom ethylbenzoate

(92%) with a melting point of 191-193 C (decomposition). Example 2:

3-Amino-4-methoxycarbonylbenzylammonium Chloride 18.5 g (0.09 mol) of methyl 4-cyano-2-nitrobenzoate and 0.93 g of palladium hydroxide (20% on charcoal) are suspended in a mixture of 8 ml of concentrated hydrochlorine acid (30% strength) and 315 ml of water in a Hastelloy autoclave with a stirrer. Then, the mixture is hydrogenated at a hydrogen pressure of 17 bar until hydrogen absorption is complete. After the pressure in the autoclave is relieved, and the catalyst is filtered, the filter is completely fine. This gives 19.5 g (97% strength) of:

3-amino-4-methoxycarbonylbenzylammonium Chloride with a melting point of .20 - 05 2 C.

Example 3:

3-Amino-4-methoxycarbonylbenzylammonium chloride:

In a stainless steel autoclave, 8 g of palladium hydroxide (20% on charcoal) and 100 ml of acetic acid are rendered inert with a gas. Then the effect is carried out with a hydrogen pressure of 17 bar. Then a solution of 0.30 g (1.455 mol) of methyl 2-nitro-4-cyanobenzoate is titrated in 2.6 L of acetic acid in a vigorously stirred mixture over

Range: 3 hours at +20°C with cooling; Using a metering pump. The pressure H is maintained at 17 bar. The pressure in the autoclave is reduced and the contents are made inert by N2. The catalyst is filtered and the filtered materials are evaporated. Output: (Acetate from the product): 91% of the theoretical amount is in the form of sticky residue. By dissolving the remainder in toluene and passing it through HCl gas (1 equivalent) at 0 to + 10 C, a quantitative precipitate of: 3-amino-4-methoxycarbonylbenzylammonium chloride is obtained, which is filtered out in the form of white crystals and dried (91% yield, melting point 204-260 AD). Example 4:

A) 3-Nitro-4-methoxycarbonylbenzylammonium chloride: 0 0 7 ml of a 1 M solution of BH3 in THF (7.0 mol) is titrated over the course of one hour at 40-50 C in a solution of 144 g (7.0 mol). from :

methyl 4-cyano-2-nitrobenzoate in 250 ml of THF and then heated with reflux for another 1.5 hours. Then the reaction mixture is treated with 600 ml of methanol saturated with hydrogen chloride gas, ice-cold, and heated with reflux for one hour. The mixture is concentrated under atmospheric pressure and re-filtered with 0.0 7 ml of methanol. The remainder that remains is stirred with 0.05 ml of ethyl acetate and filtered, and the product is dried. This gives 115 g (67%) of -3-nitro-4-methoxycarbonylbenzyl ammonium chloride with a melting point of 248-247 C. B) Methyl 4-methanesulfonylaminomethyl-2-nitrobenzoate. 9.4 ml (244.0 mol) of methanesulfonyl chloride is titrated over a period of 30 minutes with cooling on ice to a solution of 1.0 3 g (122.0 mol) of 3-nitro- 4-methoxycarbonyl-

benzylammonium chloride and 34 milliliters (244.0 mol) of triethylamine in 300 milliliters of dichloromethane, and the mixture continues to be stirred for one hour. To continue the process, the reaction mixture is treated with ice water, the phases are separated, and the aqueous phase is extracted twice more with dichloromethane. After drying (Na2SO4), filtration and concentration,

31.3 g (89%) of methyl 4-methanesulfonylaminomethyl-2-nitrobenzoate remains in the form of oil in the form of syrup.

C) methyl 2-amino-4-methanesulfonylaminomethylbenzoate: 13.25 g (46 mmol) of -2-methyl 4-methanesulfonylaminomethyl nitrobenzoate is dissolved in 0.2 milliliters of methanol. After adding 1.4 ml (4.6 ml

1 mole) of concentrated hydrochloric acid and 1 g of Pd catalyst (10% on activated charcoal). The mixture is hydrogenated with hydrogen under atmospheric pressure until hydrogen absorption is complete. The mixture is removed from the catalyst by filtration and the filtrate is completely concentrated. Crystallization of the remaining water results in 4.10 g (80%) of:

methyl 2-amino4-methanesulfonylaminomethylbenzoate with a melting point of 121-122 C.