Alpha-aryl-alpha-phenylethyl-1H-1,2,4-triazole-1-propanenitriles.
10 claims: 4 independent, 6 dependent
- 1REIVINDICAÇÕES l.~ Processo para a preparação de composições fungicidas contendo S^-aril-^-feniletil-lH-l,2,4-triazolo-l-propanonitrilos caracterizado pelo facto de se misturar infimamente uma quan :'4 tidade efectiva, compreendida entre cerca de 0,1% e cerca de 98%, de um composto fungicida que e um triazol substituído de formula geral ÇN Ar(X )ZCCHR-N X m ι \ Ar(Y n ) N N na qual ' o símbolo Z representa um grupo etileno, um grupo etenileno, !...... um grupo etinileno ou um grupo isopropileno, grupos etileno, etenilenp ou isopropileno esses que podem ser opcionalmente halogenados, ι·;-/··' E.· - : / '',· ·ΐ os símbolos Ar(X) e Ar(Y) representam estruturas de anéis m n aromáticos em ^θ-C^Q substituídos ou não substituídos ou o símbolo Ar(Y) n pode representar um anel pentagonal tendo 4 átomos de carbono e um átomo de azoto, oxigénio ou enxofre ' i: ou um anel hexagonal tendo 1 átomo de azoto e 5 átomos de car bono ou 2 átomos de azoto e 4 átomos de carbono;os símbolos X e Y são iguais ou diferentes e podem representar átomos de halogéneo ou radicais alquilo C^-Cg opcionalmente substituídos por até três ãtomos de halogéneo, alcenilo C2” C 6 opcionalmente substituído por até três átomos de halogéneo, ' ,4 . hidroxi, alcoxi C^-Οθ, alcenoxi C2~Cg, fenilo opcionalmente substituído por um ou dois átomos de halogéneo, ciano, amino, monoalquil(C^-Cg)-amino ou dialquilamino tendo independentemente 1 até 6 átomos de carbono em cada grupo alquilo, -G(0)H, SO^Z na Qual o símbolo Z representa um radical alquilo C-^-Cg ou arilo e o símbolo a representa 0, 1 ou 2, e -C(0)NR R„ na — J- z ί· Qual os símbolos R^.e R 2 , independentemente um do outro, representam átomos de hidrogénio ou radicais alquilo C -Cg;o símbolo R representa um átomo de hidrogénio ou um radical '' fenilo opcionalmente substituído por atê três átomos de halogéneo, um radical trifluorometilo ou um grupo alquilo C^-C g ;e os símbolos m e n representam, independentemente um do outro, numeros de 0 atê 3;um seu enantiomorfo, sal de adição de ácido ou complexo de sal metálico aceitável em agricultura, com um diluente ou um veículo , : . ' . i. aceitável do ponto de vista agronómico. '1
- 2“ Processo de acordo com a reivindicação 1, caracteriza :: -.Η do pelo facto de, na fórmula do composto, o símbolo Z representar um grupo de fórmula -CF^CF^-, g· símbolo AffíX^) representar um radical fenilo ou naftilo opcionalmente substituído, · - í O símbolo Ar(Y n ) representar um radical fenilo opcionalmente subs_ tituído, OS símbolos X e Y serem iguais ou diferentes e representarem átomos de halogéneo ou radicais trifluorometilo, hidroxi, metoxi, etoxi, propoxi, metilo, etilo, fenilo ou naftilo;e os símbolos m e n serem iguais ou diferentes e representarem os números 0, 1 ou 2.
- 33, - Processo de acordo com a reivindicação 1, caracterizadó pelo fac#o de, na fórmula do composto, o símbolo Z representar um grupo de fórmula -CH=CH- e os símbolos Ar(X m ) } Ar(Y ) χ γ, *-102- m e n terem os significados definidos na reivindicação 2.
- 44, - processo de acordo com a reivindicação 1, caracteriza do pelo facto de o composto ser como se definiu na reivindicação 3 em que o símbolo Z representa o isómero trans (E).
- 55, - Processo de acordo com as reivindicações 1 ou 2, caracterizado pelo facto de, na formula do composto, o símbolo X m representar hidrogénio, 2-halogéneo, 3-halogéneo, 4-halogéneo, 3-trifluorometilo, 4-trifluorometilo, 4-metoxi- 4-metilo, 4-etilo • 3,4-halogéneo;e o símbolo Y representar hidrogénio, 2-halogéneo, 3-halogeneo, 4-halogéneo, 2,6-halogéneo, 3-trifluorometilo, 2-metoxi e 2-etoxi.
- 66, - processo de acordo com a reivindicação 1, caracterizado pelo facto de o composto ser como se definiu na reivindicação 2 em que a) o símbolo X^ representa um átomo de hidrogénio e o símbolo Y R representa 4-halogeneo ou b) o símbolo representa 4-halogeneo e o símbolo Y n represen ta um atomo de hidrogénio ou 4-halogéneo ou 2-halogéneo ou 2-meto xi ou 2-etoxi ou c) o símbolo representa 2-halogéneo e o símbolo Y^ representa um átomo de hidrogéneo ou 4-halogéneo ou d) o símbolo X^ representa 3-halogéneo ou 4-halogêneo e o sím bolo Y^ representa 3-halogéneo ou e) o símbolo X^ representa 3-halogéneo e o símbolo Y n represen ta hidrogénio, 3-halogeneo, 4-halogéneo, 2-metoxi, 2-etoxi ou hidrogénio ou 4-halogéneo ou f) o símbolo X representa 4-trifluorometilo e o símbolo Y re- m n presenta hidrogénio, 4-halogéneo, 2-metoxi ou 2-etoxi ou g) o triazol substituído é um triazol designado 2-(4-clo- Ip' rofehiD-etíl -fenil-lH-1,2,4-triazol-l-propanonitrilo ou $úF 1 -C4-bromofehil)-^í’ 2-(4-clorofenil)-etil /-1H-1,2,4-triazol-l- ';/propanonitrilo ou -(2-clorofenil)-^ 2-(4-clorofenil)-etil_
- 77~ ί'-ii ,l -1H-1,2,4-triazol-l-propanonitrilo ou -£ 2-(4-clorofenil)-etil J?ÍÍJ) ·. -¾-(2-metoxifenil)-lH-l,2,4-triazol-l-propanonitrilo ou -£ 2'íi/' ' 1 T - bi?omofenil)-etil 22-^4-fenil-lH-1,2,4-triazolpropanonitrilo ou énil- X2-(4-trifluorometilfenil)-etil J-1H-1,2,4-triazolfc ”l-propanonitrilo. •7,- Método para se controlar a presença de fungos fitopatofacto de se aplicar a uma planta, ãs pelo a um habitat de plantas, uma quantidade fungicida, compreendida entre cerca $ génicos, caracterizado . sementes de plantas ou eficaz sob o ponto de vista w 1F de 3,13 g e cerca de 2242 Kg, de um composto como se definiu em Ml . uma qualquer das reivindicações 1 a 6, opcionalmente numa composi ção preparada por um processo de acordo com uma qualquer das reivindicações anteriores.
- 88,- fb?ocesso mecânico para melhorar o valor comercial e/ou L a.rentabilidade de culturas comerciáveis de plantas cujo crescifel 1 |1' ~ mento ê afectado ou ê susceptível de ser afectado por fungos, caΝ'! .:racterizado pelo facto de compreender li i BBum dispositivo de disseminação mecânica, que inclui o composto fungicida descrito .carregar para um recipiente, um dispositivo de fumigação ou uma composição fungicida de fumigação ou de disse 2. utilizar o recipiente, dispositivo * minação mecânica para aplicar a composição fungicida, sob a forma ir de grânulos, pó, fumo, vapor ou preparação líquida contendo agen‘ tes |, : tas ¢..--.1 fc·:'··. cer íi:··': fcl ϋΙ:Ί,· isiíl·ΐ;tensioactivos, a plantas em crescimento, a sementes de planou a um.,meio de desenvolvimento em que as. plantas estão a cre£ ou ao próprio fungo, ^/-1043. controlar a dose do ingrediente activo durante esta opera” .w um efeito inaceitavelmente adverso sobre as em desenvolvimento ou’a serem desenvolvidas se des fazer CN I Ar(X )ZCH ção de aplicação de modo que a taxa de aplicação do composto fun suficiente para combater o fungo mas insufigicida activo seja ciente para causar plantas de cultura na área tratada.
- 9- Processo para a preparação de um composto como creveu na reagir um .... reivindicação 1, caracterizado pelo facto de se cómposto de formula geral ρ· COin um composto de formula geral ·? em' .que :í o símbolo Z representa um grupo etileno, etenileno, ou isopropileno, o Símbolo Hal representa um átomo de halogéneo, o símbolo: X, representa um átomo de halogéneo e os símbolos Ar, X^ e Y n têm os significados definidos na reivindicaçSo 1.
- 10- Processo para a preparação de um composto que compor Uffl átomo de carbono quaternário que está ligado a um grupo ... . :arilo, a um grupo ciano e a um grupo metiltriazol, caracterizado pelo facto de se fazer reagir um composto que comporta um átomo de carbono terciário que está ligado a um grupo arilo, a um grupo ciano e a u® átomo de hidrogénio, com um halogenometiltriazol. O Agente Oficial da Propriedade Industrial
Independent claims10
1,516 paragraphs in 68 sections, as filed
DESCRIPTIVE LEMORY
The present invention relates to α-aryl-Î ± -X-phenyl-ethyl-1H-1,2,4-triaz®-1-propanenitriles, the preparation of compositions containing them and their use in the control of phytopathogenic fungi. In the compounds of the present invention the phenethyl and aryl radicals may be substituted or unsubstituted.
U.S. Patent No. 4,363,165 to Miller et al. Relates to 1-aryl-cyanoalkyl-1,2,4-triazoles and 4-aryl-cyanoalkyl-1,2,4-triazoles. triazoles and their use against phytopathogenic fungi. However, neither the phenethyl triazoles of the present invention nor the benzyl triazoles were prepared by Miller et al. Therefore, the prior art fails to recognize the particular class of compounds to which the present invention is limited and also does not mention that this class of compounds has a surprisingly high degree of fungicidal activity. Phenethyl triazoles, preferably
<img file="PT85239B_D0001.tif" />
not only effective against wheat powdery mildew, wheat stalk rust and wheat leaf rust, but are significantly superior to benzyl triazoles and phenyl triazoles in their activity against barley helminthospory, rice rust and early peanut leaf spot.
European Patent Application No. 52,424, issued May 26, 1982, generically describes a class of compounds comprising the compounds of the present invention. However, none of the present compounds have been prepared or specifically reported. In fact, none of the examples of European Patent Application No. 52,424 have a cyano group attached to the quaternary carbon atom, but include either a hydroxy, methoxy, butoxy or allyloxy group. The three phenethyl triazole compounds which have been prepared and referred to in said European Patent Application Number 52,424 are 4,4-dimethyl-3-hydroxy-3- (1,2,4-triazol-1-yl) - methyl-1- (halogen substituted phenyl) pentanes.
Published German Patent Application No. 3,216,301 discloses the fungicidal activity of alkoxytriazole propynonitriles.
European Patent Application No. 63,099 relates to the use of chloromethyltriazole to prepare a 1H-1,2,4-triazol-1-ylmethylphosphonium salt.
British Published Patent Application No. 2,119,374 relates to a process for the preparation of C 1- (alkoxy, alkenoxy, alkyoxy or phenylalkoxy) o-aryl triazolylmethyl acetonitrile compounds.
We have just discovered a novel triazole propanenitrile septum in surprising fungicidal activities. This class of compounds comprises the c-aryl-β-phenylethyl-1H-1,2-triazolo-1-propanenitrile of the general formula.
Ar (X) -Z 'm'
<img file="PT85239B_D0002.tif" />
-C-CHR — N l<sub>r (Yn)</sub> \ n = J (I) wherein Z is ethylene (-CHgCHg-), ethenylene (-CH = CH-), ethinylene (-CH = CH-)
ÇK<sub>3</sub> or an isopropylene group (-CH-CHg-), the ethylene, ethenylene or isopropylene groups may optionally be halogenated;
the Ar symbol (X<sub>m</sub>) represents a substituted or unsubstituted ring ring structure;
the symbol Ar (Y<sub>no</sub>) represents a substituted or unsubstituted aryl radical;
X and Y may be the same or different and are SOaZ, wherein Z is (C 1 to C 6) alkyl or aryl and a is 0, 1 or 2; a halogen atom, a (C1 -C6) alkyl group optionally substituted by one to three halogen, (C6 -C6) alkenyl optionally substituted by one to three
- three halogen atoms, hydroxy, (C1 -C6) alkoxy, (Cg to C6) alkenoxy, phenyl optionally substituted by one or two halogen, cyano, amino, monoalkylamino atoms having up to six carbon atoms, dialkylamino having up to six carbon atoms in each alkyl group, -C (O) H or a group of the formula wherein R 2 and R 6 independently of one another are hydrogen or alkyl;
R represents a hydrogen atom or a phenyl radical optionally substituted by one to three halogen atoms, a trifluoromethyl or (C1 -C6) alkyl group;
and the symbols m and n represent independently of each other a number from 0 to 3 ·
The new class of triazolo propanenitriles also includes the enantiomorphs, acid addition salts and metal complexes of agronomically acceptable compounds of formula (I).
The term aryl is intended to include C 6 -C 4 aromatic ring structures, a pentagonal aromatic ring having four carbon atoms and one nitrogen, oxygen or sulfur atom or a hexagonal aromatic ring having one or two nitrogen atoms and five or four carbon atoms, all optionally substituted by one to three halogen atoms, a trifluoromethyl group or a C1 -C4 alkyl group<sub>6</sub>).
alkyl term is intended to include
<img file="PT85239B_D0003.tif" />
both branched and straight chain alkyl groups, preferably C1 -C6. Typical alkyl groups which are encompassed by the use of this term include methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, pentyl, neo-pentyl, isopropyl radicals. pentyl, hexyl, heptyl and isooctyl.
The term alkoxy as used herein is intended to include alkenoxy as well as the radical consisting of an alkyl group attached to an oxygen atom. Preferred groups include (C1 -C6) alkoxy. Typical alkoxy groups that are encompassed by the term include methoxy, ethoxy, propoxy, n-butoxy, iso-butoxy, pentoxy, hexoxy and allyloxy radicals.
Acids which may be used in the preparation of acid addition salts according to the present invention include, for example, hydrochloric, hydrobromic, nitric, sulfuric, phosphoric, hydroiodic, hydrochloric, perchloric, p-toluenesulfonic acid, methanesulfonic, acetic, citric, tartaric, malic, maleic, oxalic, fumaric and italic.
Also included within the scope of the present invention are the metal salt complexes of formula
<img file="PT85239B_D0004.tif" />
Ar (Y<sub>no</sub>)
<img file="PT85239B_D0005.tif" />
in which the symbols Z, Ar (Y<sub>no</sub>), X, Y, nor have the meanings defined in general formula I and IJ represents a cation of a metal chosen in Groups os, ιβ, IIB, VIB, VIIB and VIII of Table. Periodic, and X 4 represents an anion chosen such that the sum of the valence charges of the cation M and the anion is zero.
Typical cations within the scope of the present invention are magnesium, manganese, copper, nickel, zinc, iron, cobalt, calcium, tin, cadmium, mercury, chromium, lead and barium.
Typical anions within the scope of the present invention are chloride, bromide, iodide, fluoride, sulfate, bisulfate, perchlorate, nitrate, nitrite, phosphate, carbonate, bicarbonate, acetate, citrate, oxalate, tartrate, malate, maleate, fumarate, p-toluenesulfonate, methanesulfonate, C1 -C4 monoalkyl dithiocarbamate, C1 -C4 dialkyl dithiocarbamate and C1 -C4 alkylene bisditiocarbamate.
According to a preferred aspect, the present invention comprises the compounds of formula (I) and of formula (II), their enantiomorphs, agronomically acceptable salts and complexes, wherein Z is a group. ethylene, Ar is phenyl and X and Y are hydrogen or halogen atoms or trifluoromethyl groups. In an even more preferred embodiment, the symbol Y<sub>no</sub> represents a hydrogen atom, a 2-alkoxy, 4-halogenomethyl or 3-trifluoromethyl group and X is a hydrogen atom, a 4-halogen methyl group or a
4-trifluoromethyl. Still according to another form of reaction
Preferred embodiment Y is a 2-halogen atom and X is a 4-halogen atom or Y is a 4-halogen atom and X is a 2-halogen atom . According to a further preferred embodiment X is 3-halogen and Y is hydrogen.
According to another preferred embodiment, Z represents an ethenylene group, Ar represents a phenyl group and X and Y represent hydrogen or halogen atoms or a trifluoromethyl group. According to an even more preferred embodiment Z represents an ethenylene group and Ar (X<sub>no</sub>) represents a phenyl radical substituted by a halogen atom.
Typical compounds within the scope of the present invention which have been prepared are as follows:
1. o - (4-chlorophenyl) - o - (2-phenylethyl) -1H-1,2,4-triazolo-1-one
propanenitrile;
2. -phenyl-α- (2-phenylethyl) -1H-1,2,4-triazolo-1-propanenitrile;
3 - (2-methoxyphenyl) - << - (2-phenylethyl) -1H-1,2,4-triazolo-1-propanenitrile;
4 C <- (4-Fluorphenyl) -c <- (2-phenylethyl) -1H-1,2,4-triazole
-1-propanenitrile;
5 << - (2,4-dicyiorophenyl) - - (2-phenylethyl) -1H-1,2,4-triazolo-1-propanenitrile;
6 L - (4-chlorophenyl) -1- (2- (4-chlorophenyl) ethyl) -1H-1,2,4triazolo-1-propanenitrile;
7 ° - - (4-chlorophenyl) - - / 2- (4-fluorophenyl) ethyl / -1H-1,2,4-
-triazolo-1-propanenitrile;
8 K - (4-chlorophenyl) - - / 2- (4-methylphenyl) ethyl / -1H-1,2,4-
-triazolo-1-propanenitrile:
9 C <(4-chlorophenyl) - - / 2- (4-methoxyphenyl) ethyl / -1H-1,2,4-
-triazolo-1-propanenitrile;
10 [2- (4-chlorophenyl) ethyl] -7-phenyl-1H-1,2,4-triazolo-1-propanenitrile;
11 o / [2- (4-fluorophenyl) ethyl] -1-phenyl-1H-1,2,4-triazolo-1-propanenitrile;
12 (2-phenylethyl) - X - (4-phenylphenyl) -1H-1,2,4-triazolo-1-propanenitrile;
13 N-phenyl-X- [2- (2-trifluoromethylphenyl) ethyl] -1H-1,2,4-triazol-1-propanenitrile;
14 phenyl-X- [2- (3-trifluoromethylphenyl) ethyl] -1H-1,2,4-triazolo-1-propanenitrile;
15 X- [2- (2,4-dichlorophenyl) ethyl] -X-phenyl-1H-1,2,4-triazolo-1-propanenitrile;
16 -? 2- (4-bromophenyl) ethyl? -? -Phenyl-1H-1,2,4-triazolo-1-propanenitrile;
17 - [2- (2-chlorophenyl) ethyl] - [phenyl] -1H-1,2,4-triazolo-1-propanenitrile;
18 [1- [2- (3-chlorophenyl) ethyl] -CO-phenyl-1H-1,2,4-triazolo-1-propanenitrile;
19 X-phenyl-7- [2- (4-trifluoromethylphenyl) ethyl] -1H-1,2,4-triazolo-1-propanenitrile;
<img file="PT85239B_D0006.tif" />
20 X- (4-chlorophenyl) - η 2 - (2- (3-trifluoromethylphenyl) ethyl) -1H-1,2,4-triazol-1-propanenitrile;
21 X - (4-fluorophenyl) - X - / 2- (3-trifluoromethylphenyl) ethyl / -1H-1,2,4-triazolo-1-propanenitrile;
22 - [2- (4-bromophenyl) ethyl] - X- (4-chlorophenyl) -1H-1,2,4-triazol-1-propanenitrile;
23 - (4-chlorophenyl) - [1- [2- (4-trifluoromethylphenyl) ethyl] -1H-1,2,4-triazol-1-propanenitrile;
24 - (4-fluorophenyl) - X- / 2- (4-trifluoromethylphenyl) ethyl / -1H-1,2,4-triazolo-1-propanenitrile;
25 X- [2- (4-bromophenyl) ethyl] X- (4-fluorophenyl) -1H-1,2,4'-triazol-1-propanenitrile;
26 X- [2- (4-chlorophenyl) ethyl] X- (4-fluorophenyl) -1H-1,2,4-triazol-1-propanenitrile;
27 X- [2- (3-bromophenyl) ethyl] -X-phenyl-1H-1,2,4-triazolo-1-propanenitrile;
28 X- (4-fluorophenyl) - X- [4- (4-fluorophenyl) ethyl] -1H-1,2,4-triazol-1-propanenitrile;
29 X- (2-methoxyphenyl) - X- [2- (4-fluorophenylphenyl) ethyl] -1H-1,2,4-triazolo-1-propanenitrile;
30 X- [2- (3-chlorophenyl) ethyl] - X- (4-fluorophenyl) -1H-1,2,4-triazol-1-propanenitrile;
31 X- (4-chlorophenyl) -1- (2- (3-chlorophenyl) ethyl) -1H-1,2,4-triazolo-1-propanenitrile;
32 X- (4-bromophenyl) X- (2-phenylethyl) -1H-1,2,4-triazolo-1-propanenitrile;
33 - (4-bromophenyl) -C1 - [2- (4-fluorophenyl) ethoxy] -1H-1,2,4-triazolo-1-propanenitrile;
34 - (3-chlorophenyl) - - (2-phenylethyl) -1H-1,2,4-triazole
-1-propanenitrile;
35  € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒâ € ƒX-X- (3-chlorophenyl) -? -? - 2- (4-chlorophenyl) -et 17-1H-1,2,4-triazol-1-propanenitrile;
36 C 1- (3-chlorophenyl) -1- [2- (4-fluorophenyl) ethyl] -1H-1,2,4-triazolo-1-propanenitrile;
37 - (4-bromophenyl) -4- [2- (4-chlorophenyl) ethyl] -1H-1,2,4-triazolo-1-propanenitrile;
38 - / 2- (3-bromophenyl) ethyl / - - (4-fluorophenyl) -1H-1,2,4-triazolo-1-propanenitrile;
39 4- [2- (3-bromophenyl) ethyl] -4- (4-chlorophenyl) -1H-1,2,4-triazolo-1-propanenitrile;
40 oC- (2-chlorophenyl) -4- [2- (4-chlorophenyl) ethyl] -1H-1,2,4-triazolo-1-propanenitrile;
41 - / 2- (4-chlorophenyl) ethyl], 4- (2-fluorophenyl) -1H-1,2,4-triazolo-1-propanenitrile;
42. - (4-chlorophenyl) - [1- [2- (2-fluorophenyl) ethyl] -1H-1,2,4-triazolo-1-propanenitrile;
43 X- (4-fluorophenyl) - X - / 2- (2-fluorophenyl) ethyl [1H-1,2,4-triazol-1-propanenitrile;
44. X- (2-chlorophenyl) -1- (2- (4-fluorophenyl) ethyl) -1H-1,2,4-triazol-1-propanenitrile;
45 - (2-fluorophenyl) -4- [2- (4-fluorophenyl) ethyl] -1H-1,2,4-triazolo-1-propanenitrile;
Ζ
---
46 Cz - [2- (4-chlorophenyl) ethyl] 7- (3-trifluorphenyl) -1H-1,2,4-triazol-1-propanitron;
47 - / 2- (4-chlorophenyl) ethyl] - (3-fluorophenyl) -1H-1,2,4-
triazolo-1-oropanenitrile;
48 cZ. - (2-bromophenyl) -<sup>ç</sup>Z- [2- (4-chlorophenyl) ethyl] -1H-1,2,4-triazolo-1-propanenitrile;
49 Z - / 2- (4-chlorophenyl) -ethoxy- (2-methoxyphenyl) -1H-1,2,4-triazolo-1-propanenitrile;
50 CZ- (2-phenylethyl) -CZ- (3-trifluoromethylphenyl) -1H-1,2,4-triazolo-1-propanenitrile;
51 α - (3-trifluoromethylphenyl) -CZ - [2- (3-trifluoromethylphenyl) ethyl] -1H-1,2,4-triazolo-1-propanenitrile;
52 (- (3-fluorophenyl) - [X- (2-phenylethyl) -1H-1,2,4-triazolo-1-propanenitrile;
53 Z - (3-chlorophenyl) - - / 2- (3-trifluoromethylphenyl) ethyl] -1H-1,2,4-triazolo-1-nopanenitrile;
54 - (2-bromophenyl) - - (2-phenylethyl) -1H-1,2,4-triazolo-1-propanenitrile;
55 - (2-bromophenyl) -CZ - [2- (3-trifluoromethylphenyl) ethyl] -1H-1,2,4-triazol-1-propanenitrile;
56 - (3-Fluorphenyl) -CZ - [2- (3-trifluoromethylphenyl) ethyl] -1H-1,2,4-triazolo-1-propanenitrile;
57 - (2-chlorophenyl) - - / 2- (3-trifluoromethylphenyl) ethyl / -1H-1,2,4-triazol-1-propanenitrile;
58 << - / 2- (2-methoxyphenyl) ethyl / - X. phenyl-1H-1,2,4-triazolo-1-propanenitrile;
-12 - ς
59. L- / 2- (3-methoxyphenyl) ethyl-7-phenyl-1H-1,2,4-triazole-2-one
-1-propanenitrile;
60 - / 2- (3,4-dimethoxyphenyl) ethyl / phenyl-1H-1,2,4-triazolo-1-propanenitrile;
61. << - / 2- (4-chlorophenyl) ethyl] - (4-methoxyphenyl) -1H-1,2,4-triazol-1-propanenitrile;
62. - (4-methoxyphenyl) - - (2-phenylethyl) -1H-1,2,4-triazolo-1-propanenitrile;
63 - (2-chloro-6-fluorophenyl) -? - (2-phenylethyl) -1H-1,2,4-triazolo-1-propanenitrile;
64. 6- (2-chloro-6-fluorophenyl) - - 2- (4-chlorophenyl) ethyl} -1H-1,2,4-triazol-1-propanenitrile;
65 - / 2- (4-chlorophenyl) ethyl7- (2,6-dichlorophenyl) -1H-
-1,2,4-triazol-1-propanenitrile;
66 - / 2- (3-bromophenyl) ethyl7- (3-chlorophenyl) -1H-1,2,4-
-thiazol-1-propanenitrile;
67 - / 2- (4-bromophenyl) ethyl / - - (3-chlorophenyl) -1H-1,2,4-
-triazolo-1-propanenitrile;
68 - / 2- (3-bromophenyl) ethyl / - - (3-fluorophenyl) -1H-1,2,4-
-triazolo-1-propanenitrile;
69 - / 2- (4-bromophenyl) ethyl7- (3-fluorophenyl) -1H-1,2,4-
-triazolo-1-propanenitrile;
70 -phenyl- (2-phenyl) -propyl-1H-1,2,4-triazolo-1-
propanenitrile;
71 - (3-fluorophenyl) - [2- (4-fluorophenyl) ethyl] -1H-1,2,4-triazol-1-propanenitrile;
-<sup>13</sup> - (ί
72 ¢ / - / 2- (4-Fluorphenyl) ethyl / - - (3-trifluoromethyl-phenyl) -
-1H-1,2,4-triazolo-1-propanenitrile;
73 - / 2- (1-naphthyl) ethyl-7-phenyl-1H-1,2,4-triazolo-1-propanenitrile;
74 - / 2- (4-bromophenyl) ethyl-C 4- (2-ethoxyphenyl) -1H-1,2,4-triazolo-1-propanenitrile;
75 γ - / 2- (4-bronchophenyl) ethyl] - (3-trifluorfliethylphenyl) -
-1H-1,2,4-triazolo-1-propanenitrile;
76. - (2-ethoxyphenyl) - - / 2- (3-trifluoromethylphenyl) ethyl7-
-1H-1,2,4-triazolo-1-propanenitrile;
77 - (2-ethoxyphenyl) - - (2-phenylethyl) -1H-1,2,4-triazole
-1-propanenitrile;
78 - / 2- (4-chlorophenyl) ethyl / - - (2-ethoxyphenyl) -1H-1,2,4-triazolo-1-propanenitrile;
79. - (2-ethoxyphenyl) -1- (2- (4-fluorophenyl) ethyl) -1H-1,2,4-triazol-1-propanenitrile;
80 - / 2- (3,4-dichlorophenyl) ethyl / "phenyl-1H-1,2,4-
-triazolo-1-propanenitrile;
81 - (3-chlorophenyl) - - / 2- (3-chlorophenyl) ethylZ-1H-1,2,4-
-triazolo-1-propanenitrile;
82. - (3-chlorophenyl) - - / 2- (3-fluorophenyl) -ethi / -1H-1,2,4-
-triazolo-1-propanenitrile;
83 CZ- / 2- (3-Fluorphenyl) ethyl / phenyl-1H-1,2,4-triazole
-1-propanenitrile;
84. - / 2- (3-chlorophenyl) ethyl7- (2-methoxyphenyl) -1H-1,2,4-triazolo-1-propanenitrile;
/ /
/
- 14 - k .......
<sub>(</sub>r J *
85 - (4-bromophenyl) -1,2- (2- (3-chlorophenyl) ethyl) -1H-1,2,4-
-triazolo-1-propanenitrile;
86 - (4-chlorophenyl) - - [2- (3-fluorophenyl) ethyl] -1H-1,2,4-
-triazolo-1-propanenitrile;
87. - (3-bromophenyl) - - (2-phenylethyl) -1H-1,2,4-triazole
-1-propanenitrile;
88 N - / 2- (3-bromophenyl) ethyl / - X - (2-ethoxyphenyl) -1H-1,2,4-
-triazolo-1-propanenitrile;
89 - (3-fluorophenyl) - - / 2- (3-fluorophenyl) ethyl / -1H-1,2,4-
-triazolo-1-propanenitrile;
90 - (4-bromophenyl) - - / 2- (3-bromophenyl) ethyl (-1H-1,2,4-
-thiazol-1-propanenitrile;
91. X- / 2- (3-chlorophenyl) ethyl / - X- (3-fluorophenyl) -111-1,2,4-
-triazolo-1-propanenitrile;
92 X- / 2- (3,3-S-dichlorophenyl] ethyl] -X-phenyl-1H-1,2,4-
-triazolo-1-propanenitrile;
93 - / 2- (4-methoxyphenyl) ethyl] -X-phenyl-1H-1,2,4-triazole-2-one
-1-propanenitrile;
94. · X - / 2- (4-chlorophenyl) ethyl7-phenyl-phenyl-1H-1,2,4-
-thiazol-1-propanoritrile;
(an isomer in the beta position).
95 - / 2- (4-chlorophenyl) ethyl] - X - (2-thienyl) -1H-1,2,4-
-triazolo-1-propanenitrile;
96 X- [2- (4-chlorophenyl) ethyl] 7- (2-pyridyl) -1H-1,2,4-triazol-1-propanenitrile;
~ 15 -
97 CZ-phenyl-Î ± - (e) (2-phenylethyl) -1H-1,2,4-triazolo-1-propanenitrile; and
98 -phenyl- (e) -2- (4-chlorophenyl) ethenyl-1H-1,2,4-triazolo-1-propanenitrile.
The structures of compounds 1-96 are shown in Table 1 below.
<img file="PT85239B_D0007.tif" />
<img file="PT85239B_D0008.tif" />
Compound
<img file="PT85239B_D0009.tif" />
H
<img file="PT85239B_D0010.tif" />
4C1
H
H
H
H
4G1
<img file="PT85239B_D0011.tif" />
<sup>4CH</sup>3 40CH-.
401 4F
H 2CF-. 3CF<sub>3</sub>
2.4C1
H
20CH-J
4F
2.4C1
4C1
4C1
4C1
4C1
H
H
Compound
<td> 16</td><td>4Br</td><td>H</td>
<td> 17</td><td>2C1</td><td>H</td>
<td> 18</td><td> 301</td><td>H</td>
<td> 19</td><td>4CF3</td><td>H</td>
<td> 20</td><td>3CF.</td><td> 401</td>
<td> 21</td><td>3CF.</td><td>4F</td>
<td> 22</td><td>4Br</td><td> 401</td>
<td> 23</td><td>4CFg</td><td> 401</td>
<td> 24</td><td>4CFg</td><td>4F</td>
<td> 25</td><td>4Br</td><td>4F</td>
<td> 26</td><td> 401</td><td>4F</td>
<td> 27</td><td>3Br</td><td>H</td>
<td> 28</td><td>4F</td><td>4F</td>
<td> 29</td><td>40F,</td><td>20CH</td>
<td> 30</td><td> 301</td><td>4F</td>
<td> 31</td><td> 301</td><td> 401</td>
<td> 32</td><td>H</td><td>4Br</td>
<td> 33</td><td>4F</td><td>4Br</td>
<td> 34</td><td>H</td><td> 301</td>
<td> 35</td><td> 401</td><td> 301</td>
<td> 36</td><td>4F</td><td> 301</td>
<td> 37</td><td> 401</td><td>4Br</td>
<td> 38</td><td>3Br</td><td>4F</td>
<td> 39</td><td>3Br</td><td> 401</td>
<td> 40</td><td> 401</td><td> 201</td>
<td> 41</td><td> 401</td><td>2F</td>
<td> 42</td><td>2F</td><td> 401</td>
<td> 43</td><td>2F</td><td>4F</td>
<td> 44</td><td>4F</td><td> 201</td>
<td> 45</td><td>4F</td><td>2F</td>
<td> 46</td><td> 401</td><td>3CF<sub>3</sub></td>
<td> 47</td><td> 401</td><td>3P</td>
<td> 48</td><td> 401</td><td>2Br</td>
<td> 49</td><td> 401</td><td>20CH</td>
<td> 50</td><td>H</td><td>3CF<sub>3</sub></td>
<td> 51</td><td>3CF<sub>3</sub></td><td>3OF<sub>3</sub></td>
<td> 52</td><td>H</td><td>3F</td>
<img file="PT85239B_D0012.tif" />
<img file="PT85239B_D0013.tif" />
Compound
<img file="PT85239B_D0014.tif" />
3CF<sub>3</sub>
H
3CF<sub>3</sub>
3CF<sub>3</sub>
3CF<sub>3</sub>
20CH3
3OCH<sub>3</sub>
3.40CH<sub>3</sub>
4C1
H
H
4C1
4C1
3Br
4Br
3Br
4Br
See general formula (III) below.
4F
3C1 2Br 2Br 3F 2C1
H
HH 40GH<sub>3 </sub>40CH<sub>3 </sub>201.61 * 2C1.6F 2.6C1 3Cl1C1 3F3?
3?
4F 3GF<sub>3</sub>
See general formula (IV) below.
4Br
4Br
3CF<sub>3</sub>
H 4C1 4F »401
3C1
3F
3F
3C1
301 3F H
3Br 3?
20Et
3CF<sub>3</sub>
20Et
20Et
20Et
20Et
H
3C1
3C1
H
20CH<sub>3</sub>
4Br
4C1
3Br
20Et
3F
- 18 /
Ç
Compound X<sub>m</sub> Y<sub>no</sub>
<td> 90</td><td>3Br</td><td>4Br</td>
<td> 91</td><td> 301</td><td>3F</td>
<td> 92</td><td> 3,501</td><td>H</td>
<td> 93</td><td>40CH<sub>3</sub></td><td>H</td>
<td> 94</td><td>See general formula (V) below.</td><td></td>
<td> 95</td><td>See general formula (VI) below.</td><td></td>
<td> 96</td><td>See general formula (VII) below.</td><td></td>
<img file="PT85239B_D0015.tif" />
(iii)
<img file="PT85239B_D0016.tif" />
(IV)
<img file="PT85239B_D0017.tif" />
<img file="PT85239B_D0018.tif" />
(V)
- 19 - / / / I
<img file="PT85239B_D0019.tif" />
<img file="PT85239B_D0020.tif" />
97.
<img file="PT85239B_D0021.tif" />
<img file="PT85239B_D0022.tif" />
(Compounds 97 and 93 are the isines Ξ)
<img file="PT85239B_D0023.tif" />
Other examples within the scope of the present invention are the compounds referred to in Table 2.
TABLE 2
<img file="PT85239B_D0024.tif" />
<img file="PT85239B_D0025.tif" />
Compound
Ar (Y<sub>no</sub>)
<td> 99</td><td>-ch<sub>2</sub>ch<sub>2</sub>-</td><td>-H</td><td>-0 (4CH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>C1)</td>
<td> 100</td><td>-ch<sub>2</sub>ch<sub>2</sub>-</td><td>4CH = CHF</td><td> -0</td>
<td> 101</td><td>-ch<sub>2</sub>ch<sub>2</sub>-</td><td> -0(2,401)</td><td> ~0</td>
<td> 102</td><td>-ch<sub>2</sub>ch<sub>2</sub>-</td><td>4CN</td><td>-0 (3CN)</td>
<td> 103</td><td>-ch<sub>2</sub>ch<sub>2</sub>-</td><td>4C (0) H</td><td> -0</td>
<td> 104</td><td>-ch<sub>2</sub>ch<sub>2</sub>-</td><td>4NHCH<sub>3</sub></td><td> -0</td>
<td> 105</td><td>-ch<sub>2</sub>ch<sub>2</sub>-</td><td>2SCH<sub>3</sub></td><td>-0 (4SO<sub>2</sub>CH<sub>3</sub>)</td>
<td> 106</td><td>-CH = CH-</td><td>-H</td><td>-0 (3C1)</td>
<td> 107</td><td> -0=0-</td><td>-H</td><td> -0(401)</td>
<td> 108</td><td>-CH<sub>2</sub>CH<sub>2</sub>-</td><td>4S (O) CH<sub>2</sub>CH<sub>3</sub></td><td> -0</td>
<td> 109</td><td>-chcich<sub>2</sub>-</td><td>4C1</td><td> -0</td>
<td> 110</td><td>-CHC1CHC1-</td><td>4F</td><td> -0</td>
<td> 111</td><td>-CHBrCH<sub>2</sub>-</td><td>4Br</td><td> -0</td>
<td></td><td></td><td></td><td>/ ZZrN</td>
<td> 112</td><td>-ch<sub>2</sub>ch<sub>2</sub>-</td><td>4C1</td><td>Ά \ //</td>
- 21 TABLE 2 (continued)
<img file="PT85239B_D0026.tif" />
Comparative compounds that have been prepared and tested include ·
C2a. α, α-diphenyl-1H-1,2,4-triazolo-1-propanenitrile;
C2b. -benzyl-phenyl-1H-1,2,4-triazolo-1-propanenitrile;
C6. C 1- (4-chlorobenzyl) -4- (4-chlorophenyl) -1H-1,2,4-triazolo-1-propanenitrile;
CIO - (4-chlorobenzyl) phenyl-1H-1,2,4-triazolo-1-propanenitrile.
The structures of the compounds and the comparison are as follows:
<img file="PT85239B_D0027.tif" />
CN
<img file="PT85239B_D0028.tif" />
<img file="PT85239B_D0029.tif" />
The triazoles prepared according to the present invention may be prepared by conventional general methods of synthesis. For example, triazoles may be prepared by nucleophilic displacement of o - (bromomethyl) - x - (2-phenylethyl) phenylacetonitrile (VIII) caused by a salt, preferably a salt of a triazole alkali metal, generally about 1 and about 3 equivalents. This reaction may be carried out only with the reagents or, preferably, in a suitable solvent such as dimethyl sulfoxide (DITSO), β, β-dimethylforraamide (DMF), toluene or xylene, at a temperature of about 0 ° C. to about 150 ° C, preferably from about 25 ° C to about 100 ° C.
The compound of formula VIII is prepared by bromomethylation of α-2-phenylethylphenylacetonitrile (IX) with methylene bromide (generally from about 1.1 to about 2 equivalents) under alkaline conditions, for example in the presence of sodium or potassium hydroxide, sodium hydride or potassium hydride, potassium methoxide and potassium t-butoxide (generally about 1.1 to about 2 equivalents), preferably with
<img file="PT85239B_D0030.tif" />
f use of a solvent such as DUSO in the case of sodium hydroxide or DMF in the case of hydrides and oxides at a temperature of from about 0 ° C to about 150 ° C, preferably from about 25 ° C. to about 100 ° C.
The compound of formula IX may be prepared by phase-transfer alkylation of the appropriately substituted benzyl cyanides (X), with generally about 1 to about 2 equivalents of a 2-phenylethyl methanesulfonate (mesylate) or a 2-phenylethyl-toluenesulfonate (toailate) in the presence of a strong base, eg 50% (by weight / weight) sodium hydroxide and a catalyst, for example tetrabutyl ammonium bromide (BrTBA).
The compound of formula IX may also be prepared by alkylating the appropriately substituted benzyl cyanide with about 1 to 2 equivalents of a 2-phenylethyl halide in the presence of a strong base such as metal hydrides, for example sodium hydride. or potassium hydride, using DMF / toluene as solvent. Both benzyl cyanides and alkyl halides can be readily prepared by techniques known in the literature. 0 The scheme of this synthesis is shown below.
<img file="PT85239B_D0031.tif" />
<img file="PT85239B_D0032.tif" />
Phenethyl triazole of formula (I) may be prepared directly from phenylethyl-phenylacetitrile of formula (IX) in a single. in the middle of the reaction with a halogenomethyltrysole of formula (XI) in a solvent such as DM.
<img file="PT85239B_D0033.tif" />
strong base such as sodium hydride or potassium hydride. This synthesis scheme is represented as follows:
<img file="PT85239B_D0034.tif" />
(ix)
<img file="PT85239B_D0035.tif" />
Hal-CH<sub>O</sub>-N <sup>2</sup>\ _n
NaH ------>
DMF
This of the triazoles according to may also be used for (XI) £
<img file="PT85239B_D0036.tif" />
The present invention is to prepare compounds having a quaternary carbon atom attached to an aryl group, a cyano group and a triazole group as described in U.S. Patent No. 4,366,165 θ in British Patent Application No. 2 119 374. 0 The method described in the prior art requires the additional step of preparing an arylene compound (halogenomethyl, alkylsulfonyloxymethyl or arylsulfonyloxymethyl) which is reacted with a triazole or an alkali metal triazole derivative. This extra operation is eliminated using a process according to the present invention.
The triazole acid addition salts according to the present invention may be prepared by conventional techniques well known in the art. For example, the triazole of formula (I) may be dissolved in a suitable solvent, such as diethyl ether, tetrahydrofuran, ethanol, methanol and similar solvents or combinations thereof and treated with an equivalent or an excess amount of a inorganic or organic acid which may or may not be dissolved in a suitable solvent, the mixture being then cooled or evaporated, to obtain the salt which may either be used as is or recrystallized from an appropriate solvent or a combination of suitable solvents.
The above-mentioned triazole metal salt complexes of the present invention may be prepared by adding dropwise with stirring a stoichiometric amount of a metal salt dissolved in an appropriate solvent or a combination of suitable solvents to obtain a triazole solution of formula (I) dissolved in a similarly suitable solvent or a combination of solvents. The reaction mixture is stirred for a short time and the solvent is evaporated off under reduced pressure to obtain the metal salt complex of the respective triazoles.
<img file="PT85239B_D0037.tif" />
of general formula (II).
The metal salt complexes may also be prepared by mixing stoichiometric amounts or an excess of the metal salt and a triazole of formula (I) in the desired amount of solvent containing the agents.
<img file="PT85239B_D0038.tif" />
suitable auxiliaries just before spraying ad plants. Auxiliary agents which may be included in this preparation in situ may be detergent, emulsifier, granulating, spreading, dispersing, thickening, adhesive and similar adjuvants which are used in agricultural applications.
The solvents that may be used in these methods include any polar solvents, for example water, methanol, ethanol, isopropanol or ethylene glycol and any aprotic dipolar solvents, for example dimethyl sulfoxide, acetonitrile, dimethylformamide, nitromethane or acetone.
The metal salt cations that may be used in these procedures may be selected from the group calcium, magnesium, manganese, copper, nickel, zinc, iron, cobalt, tin, cadmium, mercury, chromium, lead, barium and the like.
As a counterpoint to the metal salt, any suitable anion may be used, for example chloride, bromide, iodide, sulfate, bisulfate, phosphate, nitrate.
perchlorate, carbonate, bicarbonate, sulfhydrate, hydroxide, acetate, oxalate, malate, citrate and similar anions.
The compounds prepared according to the present invention have an asymmetric carbon atom and,
THE-
<img file="PT85239B_D0039.tif" />
28 thus * exist in the form of racemic mixtures. The enantiomorphs of these racemic mixtures may be separated by conventional techniques such as fractional crystallization with d-tartaric acid, 1-tartaric acid, 1-quinic acid and similar acids, followed by alkalinization and free base extraction of the enantiomorph d or 1 ,
Enantiomorphs, the addition salts of ►
Acid and metal salt complexes prepared in accordance with the present invention are useful as fungicidal agents for agricultural purposes and as such can be applied to various locations such as seeds, soil or foliage. For this purpose these compounds may be used in technical or pure form as they are prepared, as solutions or as formulations. The compounds are generally incorporated into a carrier and are formulated to make them suitable for subsequent dissemination as fungicides, for example, these chemical agents may be formulated as wettable powders, emulsifiable concentrates, dusting powders, granular formulations. , slippery aerosols or emulsion concentrates. In these formulations the compounds are diluted with a liquid or solid carrier and, if desired, appropriate surfactants are incorporated.
It is generally desirable, particularly in the case of foliar spray formulations, to include auxiliary agents such as wetting agents, spreading agents, dispersing agents, thickening agents, adhesives and similar adjuvants in accordance with agricultural practice. Such commonly used auxiliary agents do not.
Η /. 'in the art can be found in the John V publication.
cheon, Inc., Detergent and Emulsifiers, Annual<sup>H</sup>.
In general, compounds prepared from
<img file="PT85239B_D0040.tif" />
according to the present invention may be dissolved in certain solvents such as acetone, methanol, ethanol, dimethylformamide or dimethyl sulfoxide and such solutions may be diluted with water. Solution concentrations may range from about 1% to about 90%, with the preferred range being from about 5% to about 50%.
hi ·.
For the preparation of emulsifiable concentrates, the compound may be dissolved in appropriate organic solvents or a mixture of solvents together with an emulsifying agent which allows the fungicide to be dispersed in water. The concentration of the active ingredient in the emulsifiable concentrates is generally from about 10% to about 90% and in emulsion slippable concentrates can be as high as about 75%.
Suitable sprayable wettable powders may be prepared by mixing the compound with a dispersing agent and a finely divided solid, such as inorganic and silica clays, silicates and carbonates and optionally incorporating wetting and thickening agents into such mixtures. The concentration of active ingredients in these formulations is generally within the range of from about 20% to about 98%, preferably from about 40% to about 75%. A typical wettable powder is prepared by mixing 50 parts of O- / 2- (4-chlorophenyl) ethyl /<sup>7</sup>- oC - (2-methoxyphenyl) -1H-1,2,4-triazolo-1-propanenitrile, 45 parts of pre-hydrated silicon dioxide
<img file="PT85239B_D0041.tif" />
synthetic precipitate sold under the tradename Hi-Sil, part sodium lauryl sulphate and 5 parts sodium lignosulphonate. In another preparation, a kaolin-like clay (Barden) is used instead of Hi-Sil in the aforementioned collapsible powder and in another such preparation 25% of Hi-Sil is replaced by a synthetic sodium silica aluminate sold under the registered trademark Zeolex 7.
Dusting powders are prepared by mixing the triazoles, their enantiomorphs, their salts and complexes with finely divided inert solids which may be of an organic or inorganic nature. Materials useful for this purpose include botanical flours, silicas, silicates, carbonates and clays. A convenient method for preparing a dusting powder is to dilute a wettable powder with a finely divided carrier. Powdered concentrates containing from about 20% to about 80% active ingredient are commonly prepared and subsequently diluted to a concentration of use of from about 1 to about 10%.
The enantiomorphs, salts and complexes of the compounds prepared according to the present invention may be applied as fungicide sprays by commonly employed methods such as large volume hydraulic sprays, small volume sprays, air jet sprays. , aerial sprays and dusting powders. Dilution and application rate can be readily determined by any person skilled in the art, depending on the type of equipment used, the intended method, the timing and frequency of applications, the plants to be treated, and the diseases to be controlled. Generally, however, the fungicidal compounds prepared according to the present invention are applied in an amount of from about 1.12 kg to about 2242 kg (0.01 to 20 pounds) of active ingredient per square kilometer (per acre). when applied to the leaves or to the ground.
As a seed protective agent, the amount of compound applied to the seeds is generally from about 3.13 to about 250 grams (0.05 to 4 ounces) of active ingredient per 100 kilograms (per 100 pounds) of seed and preferably provided
6.25 to about 62.5 grams (0.1 to 1 ounce) per 100 kilograms (per 100 pounds) of seed.
As field applied fungicidal agents, the compounds may be incorporated into the field or applied to their surface generally at a dosage of from about 5.6 to about 2242 kg (0.05 to 200 pounds), preferably from about 2, 24 kg to about 1121 kg (0.02 to 10 pounds) and more preferably from about 11.21 kg to about 336.3 kg (0.1 to 3 pounds) active ingredient per square kilometer (per acre) .
As foliar fungicidal agents, the compounds are generally applied to growing plants at a dosage of from about 1.12 kg to about 1121 kg (0.01 to 10 pounds), preferably from about 2.24 kg to about 560.5 kg (0.02 to 5 pounds) and preferably from about 3.36 kg to about 112.1 kg (0.03 to 1 pound) of active ingredient per square kilometer (per acre).
The fungicides that can be combined
<img file="PT85239B_D0042.tif" />
The fungicides according to the present invention include:
<img file="PT85239B_D0043.tif" />
í | im m |.<sub>S;!</sub> g dithiocarbamates and their derivatives such as ferric dimethyl alithiocarbamate (ferbam), zinc dimethyl dithiocarbamate (manganese), ethylene bis bis dithioearbamate (maneb) and its coordination product with zinc iao zinc (mancozeb), ethylene bis bis dithiocarbamate zinc (zineb), zinc propylene bis-dithiocarbaaate (propineb), sodium methyl dithiocarbamate (aetham), tetramethyl thio urama disulphide (thiram), zineb complex and polyethylene thio urama disulphide, 3,5-dimethyl-1,2,5-2H-tetrahydrothiadiazine-2-thione (dazomet); and mixtures of these compounds with each other and copper salts thereof;
nitrophenol derivatives such as:
dinitro- (1-methylheptyl) - (dinocap), 2-sec-butyl-4,6-dinitrophenyl (binapacryl) 3,3-dimethylacrylate and 2-sec-butyl-4 isopropyl carbonate, 6-dinitrophenyl;
heterocyclic structures such as: Systhane (Rohm and Hass trademark for myclobutanyl), tridemifon, N-trichloromethylthio tetrahydro-phthalimide (caotan), N-trichloromethylthiophthalimide (folpet), 2-heptadecyl-2-imidazole acetate (glypdine), 2-octylisol -3-one, 2,4-dichloro-6- (o-chloroaniline) -s-triazine, diethyl phthalimidophosphorothioate, 4-butyl-1,2,4-triazolo, 5-amino-1- (dimethylamino) -phosphinyl] -3-phenyl-1,2,4-triazole, 5-ethoxy-3-trichloromethyl-1,2,4-triazolo, 2,3-dicyano-1,4-dithia-anthrachycin; 33 ninth (dithianon), 2-thio-1,3-dithio- / 4,5-b / quinoxaline (thioquinox), 1- (butylcarbamoyl) -2-benzimidazole (benomyl) methyl 2- (4'-thiazolyl) benzimidazole ( thiabendazole), 4- (2-chlorophenylhydrazono) -3-methyl-5-ieoxazolone, pyridine-2-thiol 1-oxide, 8-cyclooxyquinoline sulfate and its metal salts; 2,3-dihydro-5-carboxanilido-6-methyl-1,4-oxathiino, 2,3-dihydro-5-carboxanylido-6-methyl-1,4-oxathiino 4,4-dioxide, - ( phenyl) - o - (2,4-dichlorophenyl) -5-pyrimidinyl methanol (triarimol), cis-N - / (1,1,2-tetrachloroethyl) thio7-4-cyclohexene-1, 2-dicarboxyimide, 3- / 2- (3,5-dimethyl-2 *<sup>></sup>oxycyclohexyl) -2-hydroxy-7-glutarimide (cycloheximide), dehydroacetic acid, N- (1,1,2-tetrachloroethylthio) -3a, 4,7,7a-tetrahydrophthalimide (captofol),
5-1> util-2-ethylamino-4-hydroxy-6-methylpyrimidine (ethirimol), 4-cyclododecyl-2,6-dimethylmorpholine acetate (dodemorph) and 6-methyl-2-oxo-1,3 -ditiolo / 4,5-b /<sup>_ </sup>quinoxaline (quinomethionate);
<) miscellaneous »halogenated fungicides such as: tetrachlor-p-benzoquinone (chioranyl), 2,3-dichloro-1,4-naphthoquinone (dichlone), 1,4-dichloro-2,5-dimethoxybenzene (chloroneb), acid 3 , 5,6-trichloro-o-anisic (tricamba), 2,4,5,6-tetraeloro-ieophthalonitrile (TCPN), 2,6-dichloro-4-nitro-aniline (dichloran), 2-chloro-1-one nitropropane;
onitrobenzene polisher such as: pejatachloronitrobenzene (PCNB) and tetrafluordichloroacetone;
'i
e) fungicidal antibiotics such as griseofulvin, kasugamycin and eetreptomycin;
f) copper-based fungicides such as:
cuprous oxide, basic cupric chloride, basic copper carbonate, copper naphthenate and Bordeaux mixture;
e) other rice fungicides such as:
tricylazole, iso-protiolane, probenazole, propicanazole, edifenphos, 0,0-diisopropyl benzyl thiophosphate, iprodione, procimidone, vinclozolin, benomyl, methyl thiophanate, mepronil, tencycuron and validamycin A;
and
h) various fungicides such as:
diphenyl, dodecylguanidine acetate (dodine), phenylmercury acetate, N-ethyl-ercuri-1,2,3,6-tetrahydro-3,6-endoaethane-3<sub>í</sub>4,5,6,7,7-hexachlorophthalimide, phenyl mercury-amonoethanol-ammonium lactate, sodium p-dimethylain-benzenediazosulfonate, methyl isothiocyanate, 1-thiocyan-2,4-dinitrobenzene, 1-phenylthio -semicarbazide, compounds containing nickel, calcium cyanamide, lime sulfur, sulfur el, 2-bis- (3-methoxycarbonyl-2-thio ureido) -benzene (thiophanatemethyl),
Enantiomorphs, acid addition salts and metal salt complexes prepared in accordance with the present invention may be advantageously used in various ways. Because these compounds have a broad spectrum of fungicidal activity, they can be used as fungicides in lawns, orchards, plant crops, crops.<sub>J5</sub>Z ζ · grain, golf course and grain grain storage applications. Other applications of the present invention will be apparent to those skilled in the art of agriculture and horticulture.
EXAMPLES
Briefly, the substituted benzyl cyanide was converted to c-phenyl-o / (2-phenylethyl) -1H-1,2,4-triazolo-1-propanenitrile in three phases. In the first phase, benzyl cyanide was alkylated by adopting one of six<sub>r</sub> methods. In the second phase, the alkylated phenyl acetonitrile thus obtained was bromomethylated using one of four methods. Alkylated triazolo propanenitrile was synthesized from alkylated phenyl acetonitrile bromide by nucleophilic displacement with triazole potassium salt in the third phase. In the third phase, the triazole potassium salt was pre-prepared and added to the bromide, or equal parts potassium hydroxide, triazole DMSO were added to an equivalent amount of toluene, heated to 100-120 ° C for two hours. hours to distill toluene and azotropically remove water and bromide added to freshly prepared triazole potassium salt. In a third method, the triazole potassium salt was prepared in situ by the reaction of potassium triazole carbonate in a MEK or DMSO solvent.
To prepare α-phenyl-1- (2-phenylethyl) -1H-1,2,4-triazolo-1-propanenitrile, a two-step procedure can be used. The first phase is the same as the three phase procedure. However, the phase 1 product
0 '· ll
<img file="PT85239B_D0044.tif" />
It is coupled with trichloromethyltriazole.HCl in DMF via base. At least 2 equivalents of base is used. The anion is released at room temperature after
W 'WW-xx'War- “s: p>;<sup>;</sup>f ”the solid HCl salt has been added. The second equivalent releases the free base salt chloromethyl triazole which reacts with the anion. The free base may be hydroxide, alkoxide or hydride. NaOH or ΕΌΗ may be employed; however, NaH is preferred over the experimental scale. In the case of less acidic intermediate products and the anion is more difficult to form, KH is preferred.
A similar way of proceeding using chloroethyl triazole.HCl is to release the free base salt before addition. This can be done with NaOH in CH2 Cl2, then removing the solvent and adding with DMF using NaH as base or DMSO with NaOH as base.
Halogenated phenethyl triazoles may be prepared from the corresponding phenethyl triazols by reaction with n-chlorosuccinimide (NOS) or n-broaosuccinimide (NBS) in the presence of a catalyst or an initiator such as benzoyl peroxide. Phenethyl triazole is dissolved in an inert solvent, such as carbon tetrachloride, and 1 or 2 equivalents of the halogenating agent is used.
Halogenated triazoles can be transformed into ethenyl derivatives by elimination of the base using a hydroxide or a metal alkoxide. Typical bases include sodium hydroxide, sodium methoxide and potassium tert-butoxide.
<img file="PT85239B_D0045.tif" />
<img file="PT85239B_D0046.tif" />
ff
A summary of the steps and preparation process for compounds 1-96 is given in Tables 3 and 4. TABLE 3 Phase 1 Phase 2 Phase 3
<td>βί · ' </td><td>1. 50% NaOH in DMSO</td><td> 1.</td><td>50% NaOH in DMSO</td><td> 1.</td><td>KTriazolo</td>
<td>ίί ¥; ¥</td><td>or DMSO / toluene</td><td></td><td>(50% NaOH)</td><td></td><td>previamen</td>
<td></td><td>(50% NaOH)</td><td></td><td></td><td></td><td>prepare you</td>
<td> |1</td><td></td><td> 2.</td><td>60% NaH in DMF</td><td></td><td>(KTr)</td>
<td> 1</td><td>2. 60% WaH in DMF</td><td></td><td>(NaH / DMF)</td><td></td><td></td>
<td> |1</td><td>(NaH / DMF)</td><td></td><td></td><td> 2.</td><td>KOHTriazole</td>
<td> 1</td><td></td><td> 3.</td><td>60% NaH / 35% KH</td><td></td><td>(KOHTr)</td>
<td> 1'</td><td>3. 60% NaH in DMF,</td><td></td><td>in DMF (NaH / KH)</td><td></td><td></td>
<td></td><td>toluene</td><td></td><td></td><td> 3.</td><td>I<sub>2</sub>C0 / Tri-a</td>
<td> ¥.</td><td>(N & H / DMFT = 1: 2</td><td> 4.</td><td>35% KH in DMF</td><td></td><td>(K<sub>2</sub>coyTr)</td>
<td></td><td>DM-stoluene</td><td></td><td>(KH / DMF)</td><td></td><td></td>
<td></td><td>NaH / DMFt = 2.1</td><td></td><td></td><td></td><td></td>
<td> *</td><td>DMF: toluene)</td><td></td><td></td><td></td><td></td>
<td></td><td>4. 60% NaH in DMF,</td><td></td><td>Phase 2-3</td><td></td><td></td>
<td>¥<sup>:</sup>: 'i · -</td><td>benzene</td><td></td><td colspan="2">CICHgTriazolo</td><td></td>
<td>P'</td><td>(NaH / DMFB)</td><td></td><td>(CICHgTr)</td><td></td><td></td>
<td></td><td>5. 60% NaH / 35% KH</td><td></td><td></td><td></td><td></td>
<td>p ¥ ·· '. .</td><td>in DMF</td><td></td><td></td><td></td><td></td>
<td></td><td>(NaH, KH / DMF)</td><td></td><td></td><td></td><td></td>
<td>faith-;·..:'</td><td>6. 60% NaH / 35% O</td><td></td><td></td><td></td><td></td>
<td>P<sup>:</sup>¥ <sup>? </sup>l ¥ · </td><td>in SMF, toluene</td><td></td><td></td><td></td><td></td>
<td> |¥··</td><td>(NaH, KH / DMFT)</td><td></td><td></td><td></td><td></td>
<img file="PT85239B_D0047.tif" />
TABLE 4
Agreed Phase 1 Phase 2 Phase 3 Melting Point ro
<td> 1</td><td>50% NaOH</td><td>50% NaOH</td><td>KTr</td><td> 113-114</td>
<td> 2</td><td>NaH / DMF</td><td>NaH / DMF</td><td>KTr</td><td> 118-119</td>
<td> 3</td><td>NaH / DMF</td><td>50% NaOH</td><td>KTr</td><td> 105-106</td>
<td> 4</td><td>NaH / DMF</td><td>50% NaOH</td><td>KTr</td><td> 100-102</td>
<td> 5</td><td>NaH / DMF</td><td>NaH / THF</td><td>KTr</td><td> 128-129</td>
<td> 6</td><td>NaH / DMFt</td><td>50% NaOH</td><td>KOHTr</td><td> 139-140</td>
<td> 7</td><td>NaH / DMF</td><td>NaH / DMF</td><td>KTr</td><td> 144-146</td>
<td> 8</td><td>NaH / DMF</td><td>NaH / DMF</td><td>KTr</td><td> 147-148</td>
<td> 9</td><td>NaH / DMF</td><td>NaH / DMF</td><td>KTr</td><td> 124-126</td>
<td> 10</td><td>NaH / DMF</td><td>50% NaOH</td><td>KTr</td><td> 122-124</td>
<td> 11</td><td>NaH / DMF</td><td>50% NaOH</td><td>KTr</td><td> 108-111</td>
<td> 12</td><td>NAH / DMFt</td><td>50% NaOH</td><td>KTr</td><td> 168-169</td>
<td> 13</td><td>NaH / DMFt</td><td>50% NaOH</td><td>KTr</td><td> 130-131</td>
<td> 14</td><td>NaH / DMFt</td><td>50% NaOH</td><td>KOHTr</td><td> 127-128</td>
<td> 15</td><td>NaH / DMFt</td><td>50% NaOH</td><td>KOHTr</td><td> 154-155</td>
<td> 16</td><td>NaH / DMF</td><td>50% NaOH</td><td>KTr</td><td> 115-117</td>
<td> 17</td><td>NaH / DMFt</td><td>50% NaOH</td><td>KOHTr</td><td> 113-114</td>
<td> 18</td><td>NaH / DMFt</td><td>50% NaOH</td><td>KOHTr</td><td> 99-102</td>
<td> 19</td><td>NaH / DMFt</td><td>NaH / DMF</td><td>KOHTr</td><td> 133-134</td>
<td> 20</td><td>NaH / DMFB</td><td>50% NaOH</td><td>KTr</td><td> 118-121</td>
<td> 21</td><td>NaH / DMFB</td><td>50% NaOH</td><td>KTr</td><td> 85-88</td>
<td> 22</td><td>NaH / DMF</td><td>50% NaOH</td><td>KTr</td><td> 142-143</td>
<td> 23</td><td>NaH / DMFT</td><td>50% NaOH</td><td>KTr</td><td> 116-119</td>
<td> 24</td><td>NaH / DMFT</td><td>50% NaOH</td><td>KTr</td><td> 119-121</td>
<td> 25</td><td>NaH / DMF</td><td>50% NaOH</td><td>KTr</td><td> 135-137</td>
<td> 26</td><td>NaH / DMF</td><td>NaH / DMF</td><td>KTr</td><td> 121-122</td>
<td>Compound</td><td>Phase 1</td><td>Level 2</td>
<td> 27</td><td>NaH / DMFT</td><td>50 $ NaOH</td>
<td> 26</td><td>NaH / DMF</td><td>50 $ NaOH</td>
<td> 29</td><td>NaH / DMFT</td><td>50 $ NaOH</td>
<td> 30</td><td>NaH / DMF</td><td>50 $ NaOH</td>
<td> 31</td><td>NaH / DMF</td><td>50 $ NaOH</td>
<td> 32</td><td>NaH / DMF</td><td>NaH / DMF</td>
<td> 33</td><td>NaH / DMF</td><td>NaH / DMF</td>
<td> 34</td><td>NaH / DMF</td><td>NaH / DMF</td>
<td> 35</td><td>NaH / DMF</td><td>NaH / DMF</td>
<td> 36</td><td>NaH / DMF</td><td>NaH / DMF</td>
<td> 37</td><td>NaH / DMF</td><td>NaH / DMF</td>
<td> 38</td><td>NaH / DMFT</td><td>50 $ NaOH</td>
<td> 39</td><td>NaH / DMFT</td><td>50 $ NaOH</td>
<td> 40</td><td>NaH / DMF</td><td>ClCH<sub>2</sub>Tr</td>
<td> 41</td><td>NaH / DMF</td><td>ClCH<sub>2</sub>Tr</td>
<td> 42</td><td>NaH / DMF</td><td>CICHgTr</td>
<td> 43</td><td>NaH / DMF</td><td>CICHgTr</td>
<td> 44</td><td>NaH / DMF</td><td>CICHgTr</td>
<td> 45</td><td>NaH / DMF</td><td>CICHgTr</td>
<td> 46</td><td>NaH / DMF</td><td>CICHgTr</td>
<td> 47</td><td>NaH / DMF</td><td>CICHgTr</td>
<td> 48</td><td>NaH / DMF</td><td>ClCH<sub>2</sub>Tr</td>
<td> 49</td><td>NaH / DMF</td><td>CICHgTr</td>
<td> 50</td><td>NaH / DMF</td><td>CICHgTr</td>
<td> 51</td><td>NaH / DMF</td><td>CICHgTr</td>
<td> 52</td><td>NaH / DMF</td><td>CICHgTr</td>
<td> 53</td><td>NaH / DMF</td><td>ClCH<sub>2</sub>Tr</td>
* w
Phase 3 Melting Point (° O
<td>KTr</td><td> 107-108</td>
<td>KTr</td><td>oil</td>
<td>KTr</td><td>(51th</td>
<td>KOHTr</td><td>113-H4</td>
<td>KOHTr</td><td> 88-90</td>
<td>KTr</td><td> 119-120</td>
<td>KTr</td><td> 145-146</td>
<td>KTr</td><td> 95-97</td>
<td>KTr</td><td> 119-120</td>
<td>KTr</td><td> 119-120</td>
<td>KTr</td><td> 136-137</td>
<td>K<sub>2</sub>CO<sub>3</sub>/ Tr</td><td> 110-113</td>
<td>K<sub>2</sub>CO<sub>3</sub>/ Tr</td><td>oil 102-103 (ileum 122-124 102-103 110-112 oil 79-80 115-117 121-122 134-135 Glass 80-81 112-113 72-73</td>
- 40 ·£
<img file="PT85239B_D0048.tif" />
Phase 1 Compound
Phase 2 Phase 3 Melting Point (° C)
Γ:
: ί
<img file="PT85239B_D0049.tif" />
<td> 54</td><td>NaH / DMF</td><td colspan="2">CICHgTr</td><td> 118-119</td>
<td> 55</td><td>NaH / DMF</td><td>CICHgTr</td><td></td><td> 96-97</td>
<td> 56</td><td>NaH / DMF</td><td>CICHgTr</td><td></td><td> 109-110</td>
<td> 57</td><td>NaH / DMF</td><td>CICHgTr</td><td></td><td> 93-94</td>
<td> 58</td><td>NaH / DMF</td><td>CICHgTr</td><td></td><td>(51 and</td>
<td> 59</td><td>NaH / DMFT</td><td>ClCHgTr</td><td></td><td> 86-87</td>
<td> 60</td><td>NaH / DMFT</td><td>CICHgTr</td><td></td><td>oil</td>
<td> 61</td><td>NaH / DMF</td><td>NaH / DMF</td><td>KTr</td><td> 111-113</td>
<td> 62</td><td>NaH / DMF</td><td>NaH / DMF</td><td>KTr</td><td> 95-97</td>
<td> 63</td><td>NaH / DMF</td><td>NaH / DMF</td><td>KTr</td><td>Oil</td>
<td> 64</td><td>NaH / DMFT</td><td>NaH / DMF</td><td>KTr</td><td> 98-99</td>
<td> 65</td><td>NaH / DMFT</td><td>NaH / DMF</td><td>KTr</td><td> 108-109</td>
<td> 66</td><td>NaH / DMFT</td><td>NaH / DMF</td><td>KTr</td><td> 108-109</td>
<td> 67</td><td>NaH / DMFT</td><td>NaH / DMF</td><td>KTr</td><td> 112-113</td>
<td> 68</td><td>NaH / DMFT</td><td>NaH / DMF</td><td>KTr</td><td> 112-114</td>
<td> 69</td><td>NaH / DMFT</td><td>NaH / DMF</td><td>KTr</td><td> 115-117</td>
<td> 70</td><td>NaH / DMFT</td><td>CICHgTr</td><td></td><td>Oil</td>
<td> 71</td><td>NaH / DMFT</td><td>NaH / DMF</td><td>KTr</td><td> 115-116</td>
<td> 72</td><td>NaH / DMFT</td><td>NaH / DMF</td><td>KTr</td><td> 82-83</td>
<td> 73</td><td>NaH / DMFT</td><td>NaH / DMF</td><td>KTr</td><td> 108-110</td>
<td> 74</td><td>NaH, KH / DMM</td><td>KH / DMF</td><td>KTr</td><td> 130-132</td>
<td> 75</td><td>NaH / DMFT</td><td>NaH / DMF</td><td>KTr</td><td>Oil</td>
<td> 76</td><td>NaH / DMF</td><td>KH / DMF</td><td>KTr</td><td> 96-98</td>
<td></td><td>NaH / DMF</td><td>NaH / KH</td><td>KTr</td><td> 80</td>
<td> 78</td><td>NaH / DMF</td><td>NaH / KH</td><td>KTr</td><td> 126-128</td>
<td> 79</td><td>NaH / DMF</td><td>NaH / KH</td><td>KTr</td><td> 97-98</td>
- 41 Match Phase 1 Phase 2
<td colspan="2"> 80</td><td>NaH / DMFT</td><td>NaH / DMF</td>
<td></td><td> 81</td><td>NaH / DMFT</td><td>NaH / DMF</td>
<td></td><td> 82</td><td>NaH / DMFT</td><td>NaH / DMF</td>
<td></td><td> 83</td><td>NaH / DMPT</td><td>CICHgTr</td>
<td></td><td> 84</td><td>NaH / DMPT</td><td>CICHgTr</td>
<td></td><td> 85</td><td>NaH / DMFT</td><td>CICHgTr</td>
<td> 1-</td><td> 86</td><td>NaH / DMPT</td><td>CICHgTr</td>
<td></td><td> 87</td><td>NaH / DMFT</td><td>CICHgTr</td>
<td> .</td><td> 88</td><td>NaH, KH / DMF</td><td>CICHgTr</td>
<td>B.</td><td> 89</td><td>NaH / DMFT</td><td>CICHgTr</td>
<td>THE·</td><td> 90</td><td>NaH / DMPT</td><td>CICHgTr</td>
<td>í:</td><td> 91</td><td>NaH / DMPT</td><td>CICHgTr</td>
<td>fc:.,: ·</td><td> 92</td><td>NaH / DMPT</td><td>CICHgTr</td>
<td></td><td> 93</td><td>50% NaOH</td><td>50% NaOH</td>
<td></td><td> 94</td><td>50% NaOH</td><td>NaH / DMF</td>
<td>Ν ': ·'</td><td> 95</td><td>NaH / DMFT</td><td>NaH / DMF</td>
<td>r- ·· W '</td><td> 96</td><td>NaH / DMF</td><td>CICHgTr</td>
<td>- r- ·· r ..</td><td></td><td></td><td></td>
<td>Phase 3</td><td>Melting Point (° o)</td>
<td>KTr</td><td> 144-146</td>
<td>KTr</td><td> 104-106</td>
<td>KTr</td><td>98-100 100-101 103-104 96-98 126-128 (51th Oil 115-117 Oil 108-110 130-131</td>
<td>K<sub>2</sub>CO<sub>3</sub>/ Tr</td><td> 91-94</td>
<td>KTr</td><td> 244-248</td>
<td>KTr</td><td>Oil Oil</td>
ii
..
<img file="PT85239B_D0050.tif" />
Οβ melting points and elemental analysis for compounds 1 - 96 are gathered in Tables 4 and 5. The amount of chlorine, fluorine and oxygen was not determined in all examples. Nuclear magnetic resonance spectra of compounds 70, 95 and 96 are found in Table 5.
43*
<img file="PT85239B_D0051.tif" />
<td>Γ-</td><td>CM</td>
<td>ΟΟ</td><td>m</td>
<td> «*</td><td> ·*</td>
<td>ΙΑ</td><td>m</td>
<td>cn</td><td>Η</td>
<td>σχ</td><td>η</td>
<td> *</td><td></td>
<td>m</td><td>1ΓΧ</td>
η σχ xo -tf to m σχ b- οθ Ο σχ Η
<img file="PT85239B_D0052.tif" />
<td></td><td colspan="6">T -tf • k -4 ·</td>
<td>η</td><td>οο</td><td>CM</td><td>σχ</td><td>-tf</td><td>σχ</td><td>σχ</td>
<td>co</td><td>σχ</td><td></td><td>t-</td><td>cn</td><td>CM</td><td>CM</td>
<td> *</td><td> *</td><td> «*</td><td> ·»</td><td>• t</td><td>• k</td><td>• k</td>
<td>χο</td><td>-tf</td><td>cn</td><td>m</td><td>xo</td><td>lb</td><td>XO</td>
<td>Η</td><td>Η</td><td>H</td><td>H</td><td>H</td><td>H</td><td>H</td>
<td>σχ</td><td>Γ-</td><td>σχ</td><td> 00</td><td>B-</td><td>O</td><td>-tf</td>
<td>-tf</td><td>ο</td><td> 00</td><td>"THE</td><td>ox</td><td>cn</td><td>XO</td>
<td> *</td><td>• k</td><td></td><td>• k</td><td>• k</td><td>• k</td><td>• k</td>
<td>Γ-</td><td>ία</td><td>m</td><td>m</td><td>m</td><td>m</td><td>XO</td>
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<td>kk</td><td>'i'.4b</td><td> ·»</td><td></td><td>k »</td><td>• k</td><td>• k</td><td>w</td><td>k *</td><td> ·.</td><td>"B</td><td> *</td><td>Ο-</td><td> ·»</td><td>•B</td>
<td> •4<sup>1</sup></td><td> *</td><td>-tf</td><td>THE</td><td> -4</td><td>THE</td><td>THE</td><td> -4</td><td> -4</td><td>THE</td><td>-tf</td><td> -4</td><td>Χ ©</td><td>THE</td><td>xo</td>
<td>O\</td><td>THE</td><td>to</td><td>CV</td><td>THE</td><td> 00</td><td>THE</td><td>THE</td><td>ch</td><td>Ch</td><td></td><td>Ox</td><td>B-</td><td>b></td><td>CM</td>
<td>Ch</td><td>THE</td><td>to</td><td>CM</td><td>xo</td><td>xo</td><td>THE</td><td>r-4</td><td>j-</td><td>THE</td><td>r-4</td><td>Ch</td><td> 0</td><td>O</td><td>r4</td>
<td>kk</td><td>•B</td><td>• k</td><td> ·.</td><td> *</td><td>• k</td><td>Also</td><td> 9»</td><td> *</td><td> *</td><td>"B</td><td> ♦*</td><td>k »</td><td></td><td>k *</td>
<td>THE</td><td>Jt</td><td>THE</td><td>THE</td><td> -4</td><td>THE</td><td>THE</td><td> -4</td><td> -4</td><td>THE</td><td>-tf</td><td>THE</td><td>X ©</td><td>X ©</td><td>x ©</td>
<td>to</td><td>CV</td><td>O</td><td> •4</td><td>CM</td><td>THE</td><td>XO</td><td>THE</td><td>CM</td><td>THE</td><td>CM</td><td> 00</td><td>r4</td><td>THE</td><td>THE</td>
<td>THE</td><td>H</td><td>to</td><td>THE</td><td> 0</td><td>THE</td><td>Ch</td><td>XO</td><td>ch</td><td>O</td><td>σχ</td><td>Ό</td><td>CM</td><td>THE</td><td>Ch</td>
<td> «</td><td> '$·*</td><td> •</td><td> »></td><td></td><td></td><td> *</td><td> «></td><td>k »</td><td> —</td><td>Also</td><td>«X</td><td>• k</td><td>t »</td><td>•B</td>
<td>Ch</td><td>4t</td><td> -4</td><td>THE</td><td>THE</td><td>B-</td><td>O</td><td>Ch</td><td>Ch</td><td>THE</td><td>H</td><td>Ch</td><td>CM</td><td>CM</td><td> 00</td>
<td>THE</td><td>X ©</td><td>THE</td><td>XO</td><td>X ©</td><td>THE</td><td>B-</td><td>THE</td><td>THE</td><td>THE</td><td>XD</td><td>THE</td><td>B-</td><td>B-</td><td>XO</td>
<td>H</td><td>THE</td><td>B-</td><td>XO</td><td>THE</td><td>CM</td><td>H</td><td>H</td><td>THE</td><td>THE</td><td>ΓΊ</td><td>r4</td><td>THE</td><td>THE</td><td>B-</td>
<td>THE</td><td>«I</td><td>to</td><td> -4</td><td>to</td><td>THE</td><td>CM</td><td>THE</td><td> 00</td><td> -4</td><td> 00</td><td>THE</td><td>CM</td><td>CM</td><td>THE</td>
<td> —</td><td></td><td> ·></td><td></td><td> ·.</td><td>•B</td><td>•B</td><td> «*></td><td>4b</td><td>k *</td><td>"H</td><td></td><td>Vb</td><td>flb</td><td>• k</td>
<td>crx</td><td> .4</td><td> -4</td><td>THE</td><td> .4</td><td>B</td><td>H</td><td>OX</td><td>Ch</td><td>THE</td><td>H</td><td>Ch</td><td>CM</td><td>CM</td><td>Ch</td>
<td>THE</td><td>X ©</td><td>THE</td><td>XO</td><td>xo</td><td></td><td>B-</td><td>THE</td><td>THE</td><td>THE</td><td>XO</td><td>THE</td><td>b ~</td><td>B-</td><td>X ©</td>
<img file="PT85239B_D0058.tif" />
66,09 66,31 5,26 5,37 13,76 13,73 4,64 4,21 10,00 9,92
<img file="PT85239B_D0059.tif" />
<img file="PT85239B_D0060.tif" />
<td>S0</td><td>σχ</td><td>«Η</td><td> -4</td><td>Η</td>
<td>Α</td><td>Οχ</td><td>THE</td><td>χχ</td><td>ΓΛ</td>
<td> ·»</td><td>«K</td><td> ·*</td><td>• k</td><td> ·*</td>
<td>m</td><td>m</td><td>m</td><td>Η</td><td></td>
Η
<td>ΧΟ</td><td>σχ</td><td>X ©</td><td> -4*</td><td>x ©</td>
<td>σχ</td><td>σχ</td><td>σχ</td><td>CM</td><td>σχ</td>
<td> ··</td><td></td><td>• k</td><td> «»</td><td>«Κ</td>
<td>χχ</td><td>XX</td><td>in</td><td>THE</td><td>χχ</td>
Η
<td colspan="2"></td><td colspan="3">the σχ ·> 00 ι — 1</td><td>Η σχ * »Ο CM</td>
<td></td><td></td><td></td><td>σχ</td><td></td><td>χο</td>
<td></td><td></td><td></td><td>CM</td><td></td><td>σχ</td>
<td></td><td></td><td></td><td></td><td></td><td>• k</td>
<td></td><td></td><td></td><td>σχ</td><td></td><td>ο</td>
<td></td><td></td><td></td><td>Η</td><td></td><td>CM</td>
<td></td><td></td><td rowspan="3">,. CM ./. w</td><td>ο</td><td>σχ</td><td></td>
<td>xo</td><td>σχ</td><td>Ο</td><td>οχ</td><td></td>
<td>σχ</td><td>cm</td><td></td><td> *</td><td></td>
<td>· * 'The</td><td>• O</td><td><sup>r</sup>'- «Γ OX</td><td> 00</td><td>σχ</td><td></td>
<td>THE</td><td>H</td><td></td><td></td><td></td><td></td>
<td>A r4</td><td> 8</td><td>t- '0'</td><td>σχ ΜΓΧ • k</td><td>ο ο *</td><td></td>
<td> ·></td><td></td><td rowspan="2"><sup>X</sup> ch <.! .</td><td>αο</td><td>ο</td><td></td>
<td>O\</td><td>O</td><td></td><td>Η</td><td></td>
<td>H</td><td>THE</td><td></td><td></td><td></td><td></td>
ΓΧ *
<td></td><td colspan="2"> Ç·-· -W</td><td colspan="4">χο σχ • k -4</td>
<td>οο</td><td>CM</td><td>J ·</td><td>σχ</td><td> -4</td><td> .4</td><td>χο</td>
<td>Η</td><td>Ο</td><td></td><td>CXI</td><td>σχ</td><td>χο</td><td>XX</td>
<td> ·«</td><td>• ι</td><td> »</td><td></td><td> ·»</td><td> ·»</td><td></td>
<td>XX</td><td>χ ©</td><td>Γ-</td><td>χχ</td><td>σχ</td><td>XX</td><td>σχ</td>
<td>Η</td><td>Η</td><td>Η</td><td>Η</td><td>Η</td><td>Η</td><td>Η</td>
<td>Ο</td><td>Ο</td><td>Ο</td><td>οο</td><td> 00</td><td>Ο</td><td>Ο</td>
<td>Η</td><td>Λ</td><td>χχ</td><td>CXi</td><td> -4</td><td>αθ</td><td>Γ-</td>
<td> ·></td><td>• k</td><td> ·></td><td></td><td></td><td> ·»</td><td> *</td>
<td>χχ</td><td>χχ</td><td>Γ-</td><td>XX</td><td>σχ</td><td>XX</td><td> -4</td>
<td>Η</td><td>Η</td><td>Η</td><td>Η</td><td>Η</td><td>Η</td><td>Η</td>
<td>Γ-</td><td>χχ</td><td>ΧΟ</td><td>XX</td><td> 00</td><td>χχ</td><td>Η</td>
<td>Η</td><td>Η</td><td>σχ</td><td>CXi</td><td>Γ—</td><td>οο</td><td>XX</td>
<td> *</td><td> ·.</td><td> ·></td><td></td><td></td><td> ·.</td><td></td>
<td> -4</td><td>J *</td><td>XX</td><td>XX</td><td>σχ</td><td> .4</td><td> -4</td>
<td></td><td>XX</td><td>XX</td><td>CM</td><td>αο</td><td>XX</td><td>Ο</td>
<td>σχ</td><td>χχ</td><td>σχ</td><td>CM</td><td> 00</td><td>XX</td><td>XX</td>
<td> •</td><td> ·></td><td> ·></td><td> *</td><td></td><td> ·></td><td></td>
<td></td><td> -4</td><td>XX</td><td>XX</td><td>σχ</td><td> -4</td><td> -4</td>
<td>ΧΟ</td><td>CM</td><td>Ο</td><td>σχ</td><td>Η</td><td>χχ</td><td>ΧΟ</td>
<td>Η</td><td>σχ</td><td>CM</td><td>χχ</td><td> 00</td><td>σχ</td><td>XX</td>
<td></td><td></td><td></td><td>• k</td><td></td><td></td><td></td>
<td>Η</td><td></td><td>f — 1</td><td>XX</td><td> -4</td><td> -4</td><td>αο</td>
<td>X ©</td><td>χο</td><td>Γ-</td><td>ΧΟ</td><td>XX</td><td>χο</td><td>XX</td>
<td> -4</td><td>ο</td><td>Η</td><td>χο</td><td>Γ-</td><td>Ο</td><td>σχ</td>
<td></td><td>σχ</td><td>(Μ</td><td> -4</td><td>ΟΟ</td><td>σχ</td><td>αο</td>
<td></td><td></td><td>• k</td><td>• k</td><td></td><td> ·»</td><td> *»</td>
<td>Η</td><td> •4</td><td>Α</td><td>XX</td><td> -4</td><td> -4</td><td>σχ</td>
<td>ΧΟ</td><td>χο</td><td>r-</td><td>χο</td><td>χχ</td><td>χο</td><td>XX</td>
<td>σχ</td><td colspan="4">Η</td>
<td>χο</td><td>ΧΟ</td><td></td><td></td><td></td>
<td>• k</td><td>• k</td><td></td><td></td><td></td>
<td>Γ-</td><td> -4</td><td></td><td></td><td></td>
<td>Η</td><td>σχ</td><td></td><td></td><td></td>
<td>Q</td><td> -4</td><td></td><td></td><td></td>
<td>αδ</td><td>Γ—</td><td></td><td></td><td></td>
<td> ·»</td><td>• k</td><td></td><td></td><td></td>
<td> 00</td><td></td><td></td><td></td><td></td>
<td>Η</td><td>cn</td><td></td><td></td><td></td>
<td></td><td></td><td>χο</td><td>C0</td><td>CM</td>
<td></td><td></td><td>σχ</td><td>ο</td><td>Γ—</td>
<td></td><td></td><td>• k</td><td>• k</td><td>• k</td>
<td></td><td></td><td>σ \</td><td>Ctx</td><td> 00</td>
<td></td><td></td><td></td><td>Η</td><td></td>
<td></td><td></td><td>Η</td><td> -4</td><td>Η</td>
<td></td><td></td><td>Ο</td><td>Α</td><td>χο</td>
<td></td><td></td><td> *></td><td> ·»</td><td></td>
<td></td><td></td><td>Ο</td><td>σ \</td><td> 00</td>
<td></td><td></td><td>Α</td><td>Α</td><td></td>
Η
CM χχ
<td></td><td colspan="7"></td><td></td>
<td>χο</td><td></td><td></td><td></td><td></td><td>CXi</td><td></td><td> 4</td><td>d</td>
<td>Γ—</td><td></td><td></td><td></td><td></td><td> 00</td><td></td><td>φ</td><td>φ</td>
<td> ·></td><td></td><td></td><td></td><td></td><td> ·></td><td></td><td>H</td><td>H</td>
<td>σχ</td><td></td><td></td><td></td><td></td><td> -4*</td><td></td><td>Q</td><td>O</td>
<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td> 5</td><td> 3</td>
<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>G</td><td>Ç</td>
<td>χο</td><td>χο</td><td>t-</td><td>CM</td><td>xo</td><td>σχ</td><td>H</td><td></td><td></td>
<td>XX</td><td> -4</td><td>σχ</td><td>XX</td><td>O</td><td>O</td><td>σχ</td><td>QC</td><td>all</td>
<td></td><td>• k</td><td>• k</td><td></td><td> ·></td><td>• k</td><td>* k</td><td>O</td><td>υ</td>
<td>Η</td><td>χο</td><td>THE</td><td>XX</td><td>XX</td><td>xo</td><td>CM</td><td>H</td><td>H</td>
<td>Η</td><td>Η</td><td>THE</td><td>H</td><td>H</td><td>H</td><td>H</td><td> +></td><td>-P</td>
<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>'Φ</td><td>'Φ</td>
<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>Ç</td><td>Ç</td>
<td> 00</td><td>σχ</td><td> 00</td><td>O</td><td>σχ</td><td>Γ-</td><td> 00</td><td>t <0</td><td>t * D</td>
<td>Η</td><td>XX</td><td>THE</td><td> 00</td><td>O</td><td>ΟΟ</td><td>XX</td><td>all</td><td><d</td>
<td></td><td>• k</td><td>• k</td><td></td><td>• k</td><td>• k</td><td></td><td>ε</td><td>AND</td>
<td>σχ</td><td>ΧΟ</td><td>CM</td><td>XX</td><td>XX</td><td>XO</td><td>σχ</td><td></td><td></td>
<td>Η</td><td>Η</td><td>THE</td><td>H</td><td>H</td><td>H</td><td>H</td><td>ed</td><td>CD</td>
<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>laugh</td><td>you</td>
<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>O</td><td>O</td>
<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>Ç</td><td> ©</td>
<td>σχ</td><td>σχ</td><td>THE</td><td>CXi</td><td>CXi</td><td>Ox</td><td>CM</td><td><cd</td><td><cd</td>
<td> -4</td><td> 00</td><td>C *></td><td>XO</td><td>XX</td><td>σχ</td><td>H</td><td> ©</td><td>β</td>
<td> ·></td><td>• k</td><td>• k</td><td></td><td> ·></td><td></td><td> ·></td><td> 0</td><td>O</td>
<td>XX</td><td> -4-</td><td>cn</td><td> -4</td><td> -4</td><td>xo</td><td>XX</td><td><n</td><td>no</td>
<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td> ®</td><td>no</td>
<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>φ</td><td>φ</td>
<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>L</td><td></td>
<td>οο</td><td>B-</td><td>THE</td><td>H</td><td>H</td><td>XO</td><td>σχ</td><td></td><td></td>
<td>σχ</td><td>t-</td><td></td><td>XX</td><td>σχ</td><td>O</td><td>O</td><td>φ</td><td>φ</td>
<td>• k</td><td>• k</td><td>• k</td><td> ·*</td><td> ·»</td><td></td><td>• k</td><td>Ό</td><td>Ό</td>
<td> -4</td><td> -4</td><td>σχ</td><td> 4</td><td> -4</td><td>xo</td><td>XX</td><td></td><td></td>
<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>O</td><td> 0</td>
<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>G</td><td></td>
<td>Ο</td><td>t ***</td><td>σχ</td><td>O</td><td> -4</td><td>XX</td><td>σχ</td><td> +></td><td> +></td>
<td> -4</td><td> 00</td><td>χο</td><td>H</td><td>XX</td><td>XX</td><td>O</td><td> 0</td><td>O</td>
<td></td><td>• k</td><td>• k</td><td></td><td></td><td> »</td><td>• k</td><td>Φ</td><td>Φ</td>
<td> 00</td><td>Γ-</td><td>σχ</td><td> -4</td><td>H</td><td>CXi</td><td>CM</td><td>ft</td><td>The</td>
<td>XX</td><td>ΧΟ</td><td> -4</td><td>χο</td><td>X ©</td><td>AND-</td><td>AND-</td><td>no</td><td>no</td>
<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>φ</td><td>φ</td>
<td>οο</td><td>σχ</td><td>Γ—</td><td>H</td><td>XX</td><td> -4</td><td>σχ</td><td> 0</td><td> 0</td>
<td>CM</td><td> -4</td><td>χχ</td><td>σχ</td><td> -4</td><td>hp</td><td>r—</td><td></td><td></td>
<td></td><td></td><td>• k</td><td></td><td>• k</td><td> *</td><td>• k</td><td>OH</td><td>k</td>
<td>σχ</td><td>Γ-</td><td>σχ</td><td> -4</td><td>THE</td><td>CXi</td><td>CM</td><td>φ</td><td>φ</td>
<td>XX</td><td>χο</td><td> -4</td><td>XO</td><td>XO</td><td>Γ-</td><td>t-</td><td> ></td><td> ></td>
σχ ο αο σχ
Η CM σχ -4 XX ΧΟ σχ σ \ σχ σχ σχ σ \ 'The nuclear magnetic resonance spectrum of compounds 70 * 95 and 96 was plotted. The results obtained were as follows:
Compound 70: nuclear magnetic resonance spectrum (90 MHz) (mixture of diastereoisomers)
1.2 - 1.6 (two doublets, JH), 2.4 - 2.8 (m, 3H), 4 * 6 - 4.9 (two overlapping ABq, 2H), 7.0 - 7.8 ( a, 10H), 7.90 (s, 1H) and 8.0 (s, 1H).
Camposto 95: nuclear magnetic resonance spectrum (90 MHz): 2.0 - 2.4 (m, 4H), 4.8 (ABq, 2H), <sup>?</sup> 6.9 - 7.4 (m, 7H), 7.8 (s, 1H) and 7.9 (s, 1H).
Camposto96: nuclear magnetic resonance spectrum (90 MHz) δ 2.2 - 2.9 (m, 4H), 4.7 - 5.0 (ABq, 2H), 7.0 - 7.4 (ABq, 4H) , 7.4 - 7.8 (m, 3H) and 8.6 - 8.7 (broad d, 1H).
The following examples are examples of preparation of typical compounds according to the present invention.
<img file="PT85239B_D0061.tif" />
III.J jj | COMPOSITION OF THE COMPOUND 14-O-phenyl- << -Z2- (3-trifluoromethylphenyl) -et117-1,2,4-triazoIs-1-propanenitrile
Step 1 - Preparation of - / 2- (3-trifluoromethylphenyl) ethyl / phenyl acetonitrile
A round bottom flask was charged with
500 Four-necked ml with 11.0 grams of 60% NH (0.275 mole, 1.1 equivalents) was washed twice with
xane, in the street-free DMF. The reaction mixture was cooled to 0 ° C and a solution of 29.4 grams of benzyl cyanide (0.25 mol, 1.0 equivalent) in 50 ml of toluene was added dropwise. The reaction mixture was allowed to warm to room temperature and then cooled to -20 ° C and 52 grams (0.25 mol, 1.0 equivalent) of sodium chloride was added dropwise. 3-trifluoromethylphenethyl in 50 ml DMF. The reaction mixture was stirred at -20 ° C for three hours, after which gas-liquid chromatography showed 60% monoalkylation and 40% dialkylation. The reaction was quenched with water and extracted with ether. After drying and concentrating, the crude product was chromatographed by high performance liquid chromatography, taken with hexane: ethyl acetate (95: 5) and afforded.
19.2 grams of 97% pure product pipeline (26.3% yield). The mixture was used directly in the next step.
Nuclear magnetic resonance spectrum (60 1.1 Hz);
Δ 2.0 - 2.4 (m, 2H), 2.7 - 3.0 (m, 2H),
3.6 - 3.9 (t, 1H) and 7.2 - 7.4 (d, 9H).
Step 2 - Preparation of 1-Bromo-2-cyano-2-phenyl-4- (3-trifluoromethyl-phenyl) -butane.
To a 500 ml four-necked round bottom flask was introduced 19.0 grams of o - - / 2- (3-trifluoromethylphenyl) ethyl / phenyl acetonitrile (0.064 mol, 1.0 equivalent) and 17 grams of (0.097 mol, 1.5 equi.
valves) in 50 ml DMSO. The reaction mixture was stirred at room temperature and 10.3 was added dropwise.
- 51 - <
/ grams 50% NaOH (0.128 mole, 2.0 equivalents). The reaction mixture was warmed to 50 ° C and stirred for two hours. The reaction mixture was treated with water and ether and after drying and concentrating gave 25 grams of product which was used directly in the triazole coupling (96.9% yield).
Nuclear magnetic resonance spectrum (60 MHz):
2.2 - 2.8 (m, 4H), 3.7 (s, 2H) and
7.2 - 7.6 (m, 9H).
►
Step 3 - Preparation of α-phenyl-X- [2- (3-trifluoromethylphenyl) ethyl] -1,2,4-triazolo-1-propanenitrile.
In a 250 ml four neck roundwashing flask, 4.05 grams of 87% KOH (0.062 mol, 1.25 equivalents) and 4.8 grams (0.068 mol,
2.2 equivalents) triazole in 25 ml DMSO. The reaction mixture was heated to 90 ° C until homogeneous and 25 ml of toluene was added and azeotropically distilled for four hours. Toluene was distilled off at 165 ° C, the reaction mixture was cooled to 100 ° C and 12.5 grams of 1-bromo-2-cyano-2-phenyl-4- (3-trifluoromethylphenyl) was added. ) -butane (0.031 mole, 1.0 equivalent). The reaction mixture was heated at 125 ° C for one hour and then treated with water and ethyl acetate, dried and concentrated. Purification by high pressure liquid chromatography with hexane: ethyl acetate (1 · 1) yielded 8.8 grams of a white solid with a melting point of 127 ° - 128 ° C (76.7% yield) .
<img file="PT85239B_D0062.tif" />
Infrared Spectrum (nujol, cra<sup>-</sup>^) ·
<td> 2980</td><td>(s),</td><td> 2240</td><td>(w),</td><td> 1430</td><td>(s),</td><td>I38O</td><td>(s),</td>
<td> 1330</td><td>(s),</td><td> 1280</td><td>(m)</td><td> 1200</td><td>(m)</td><td> 1160</td><td>(s),</td>
<td> 1140</td><td>(s),</td><td> 1130</td><td> (6),</td><td> 1120</td><td>(s),</td><td> 1075</td><td>(m)</td>
1025 (w), 800 (m), 710 (s) and 670 (s).
Nuclear magnetic resonance spectrum (60 MHz)?
δ 2.4 - 2.9 (m, 4H), 4.6 (s, 2H),
7.3 - 7.5 (s, 4H), 7.7 (s, 1H) and
7.9 (s, 1H).
Elemental Analysis: θ20 ^ 17<sup>Ν</sup>4^3
Theoretical values (0): C 64.83; H 4.63; N, 15.14; F 15.39
Determined values (%): 0 65.13; H 4.52; N 15.09; F 15.22.
PREPARATION COMPOUND 20 <x- (4-chlorophenyl) - / 2- (3-trifluoromethylphenyl) ethyl / -1,2,4-triazolo-1-propanenitrile
Step 1 - Preparation of 1- [2- (3-Trifluoromethylphenyl) ethyl] -4-chlorophenylacetonitrile.
In a 500 ml one neck round bottom flask, 4.4 grams of 600 NaH (0.11 mole, 1.0 equivalent), washed three times with 25 ml hexanes, in 100 ml were charged. 2: 1 benzene / DMF ratio. Then 15.1 grams (0.10 mole, 1.0 equivalent) of 4-chlorobenzyl cyanide was added and stirred at room temperature for two hours. While stirring at room temperature, it was added dropwise
20.8 grams (0.1 mole, 1.0 equivalent) of 3- (4'-fluoromethyl) -phenyl chloride for a few hours and then stirred at room temperature overnight. The product was treated with water and ether and distilled after concentrating to give 16.2 grams of product (50.1% yield).
Nuclear magnetic resonance spectrum (60 TIHz)?
δ 2.0 - 3.0 (m, 4H), 3.5 - 3.8 (t, 1H),
7.3 (s, 4H) and 7.5 (s, 4H).
Step 2 - 1-Bromo-2-cyano-2- (4-chlorophenyl) -4 '- (3-trifluoromethylphenyl) -butane pre-preparation.
16.2 grams (0.05 mole, 1.0 equivalent) of << - / 2- (3-trifluoromethylphenyl) ethyl / -4- was charged to a 300 ml round necked single necked flask. chlorophenylacetonitrile and 17.4 grams of C13 Brg (0.10 mol, 2.0 equivalents) in 50 ml DMSO. The reaction mixture was stirred at room temperature and 10 grams of 50% NaOH was added dropwise, observing an exothermic reaction. The reaction mixture was stirred for forty-five minutes and gas-liquid chromatography showed that the reaction was complete. The product was treated with ether and water. Drying and elimination of solvent gave 20.8 grams of yellow oil (100% yield).
Nuclear magnetic resonance spectrum (60 MHz):
δ 2.0 - 3.2 (m, 4H), 3.8 (s, 2H)
7.5 - 7.6 (d, 10H).
Step 3 - Preparation of o - (4-chlorophenyl) - / 2- (3-trifluoromethylphenyl) ethyl [1,2,4-triazolo-1-oropanonitrile].
In a 500 ml round necked single-necked flask, 10.7 grams of triazole potassium salt (0.10 mol, 4.0 equivalents), 75 ml DIISO and 1-bromo-2-cyano were charged. -2- (4-chlorophenyl) -4- (3-trifluoromethylphenyl) butane (10.4 grams, 0.025 mol, 1.0 equivalent). The reaction mixture was heated at 80 ° C overnight and then cooled by adding 1 liter HgO and extracted three times with 200 ml ether, the ethereal extracts were washed after combining with water and water. brine, then dried and evaporated on a rotary evaporator to give a crude orifice which was suspended in ether-hexane (1-1). A solid was washed with hexane to give 5.0 grams of a light yellow solid having a melting point of 118 ° - 121 ° C (47% yield).
Nuclear magnetic resonance spectrum (60 MHz)
2.4 - 3.2 (m, 4H), 5.0 - 5.2 (broad s, 2H),
7.6 - 7.9 (broad s, 8H) 8.1 (s, 1H) and
8.4 (s, 1H).
Elemental Analysis
Theoretical values (%): C 59.32; H 3.99; N 13.85; 01 8.76;
F 14.09
Determined values (%): 0 59.46; H 4.20; N 13.25; Cl 9.48;
F 13.36.
Preparation of COMPOUND 44- (2-Chlorophenyl) - - / 2- (4-fluorophenyl) ethyl7,2,4,4-triazolo-1-propanenitrile
Step 1 - Preparation of 2- (4-Fluorphenyl) ethyl methanesulfonate. Mesylation of 2- (4-fluorphenyl) -ethanol.
In a 500 ml three-neck round bottom flask under stirring under nitrogen, equipped with condenser and funnel, 42.04 grams of 2- (4-fluorophenyl) -ethanol (0.3 1.0 eauiv-Try) in 100 ml of tetrahydrofuran (THF). The reaction mixture was cooled to 10 ° C and 60.7 grams (0.60 mole, 2.0 equivalents) of triethylamine was added directly. This was followed by the dropwise addition of 68.73 grams (0.6 mole, 2.0 equivalents) of methanesulfonyl chloride in 30 mL of THF, keeping the temperature below 30 ° C. An additional 150 ml of THF was added and the reaction mixture was stirred for six hours. The reaction mixture was cooled with water (200 mL) and ether (300 mL) was added. The ether was washed with 75 ml 10% HCl, twice with 50 ml saturated NaHCO3 and twice with 50 ml water. It was dried and concentrated to give 58.0 grams of a brown liquid (88.7% yield).
Nuclear magnetic resonance spectrum (90 MHz):
S 2.9 (s, 3H), 2.9 - 3.2 (m, 2H), 4.2 - 4.4 (t, 2H) and 6.9 - 7.4 (m, 4H).
/ »
Step 2 - Preparation of C 1- [2- (4-Fluorphenyl) ethyl] -2-chloro-phenylacetonitrile.
In a four neck 300 ml round bottom flask, 4.26 grams of 60% NaH (0.105 mole, 1.05 equivalents), washed three times with ml of hexane, in 60 ml of DMF. Then 15.16 grams (0.10 mol, 1.0 equivalent) of 2-chlorophenyl acetonitrile was added in 40 ml DMF and stirred for one hour at 10 ° C. Then methanesulfonate of
I 2- (4-fluorophenyl) ethyl (22.2 grams, 0.102 mol) in 50 ml of
DMF, drop by drop. The reaction was completed within two hours and cooled with 10 ml of 10% HCl. Then 60 ml of water was added and extracted with 200 ml of ether which was then washed twice with 50 ml of 10% HCl, dried and concentrated. 27.15 grams of the crude product was distilled off under reduced pressure to give 17.46 grams of an oil with a boiling point of 180 ° - 188 ° C at 1 mm Hg (63%). 5% yield).
Nuclear magnetic resonance spectrum (90 MHz) δ 2.2 - 2.4 (t, 2H), 2.8 - 3.0 (m, 2H),
3.8 - 3.9 (t, 2H) and 6.9 - 7.5 (m, 8H).
Step 3 ** Preparation of oC - (2-chlorophenyl) - CZ - [2- (4-fluorophenyl) ethyl] -1,2,4-triazolo-1-propanenitrile.
In a 200 ml three-neck round-bottom flask, 2.3 grams of βθΑ NaH (0.055 mole, 2.75 equivalents) washed twice with 25 ml of hexane in 40 ml of D were charged. .'F. The mixture was cooled
- 57 <sup>!</sup>v .....
The reaction mixture was cooled to 10 ° C and 5.46 grams (0.02 mole, 1.0 equivalent) of '- - (2- (4-fluorophenyl) ethyl / -2-) was added dropwise. chlorophenyl acetonitrile in 40 ml DLH ™ for 10 minutes. After twenty minutes, 3.12 grams (0.0204 mole, 1.02 equivalents) of chloromethyltriazole.HCl were added directly in two portions. After one hour, the gas-liquid chromatography assay indicated that the reaction was complete and the reaction was stopped by slowly adding 20 ml of water. The product was extracted with 200 mL of CH2 Cl2 and washed twice with 50 mL of water. After drying and concentrating, an orange oil was obtained which crystallized from ethyl ether. The product was filtered and 2.5 grams of a light brown solid melting at 110 ° - 112 ° C (35% yield) was obtained.
Infrared Spectrum (nujol, cm<sup>-</sup>”<sup>1</sup>) í
1505 (m), 1440 (s), 1370 (m), 1270 (m), 1220 (m), 1130 (m) and 750 (m).
Nuclear magnetic resonance spectrum (90 MHz) δ 2.2 - 3.0 (m, 4H), 3.6 - 4.2 (ABq, 2H),
6.9 - 7.4 (m, 7H), 7.8 (s, 1H) and
7.9 (s, 1H).
Elemental Analysis C C ^HH gNNFGl
Theoretical Values ($): 064.30; H 4.55; N15.0; F5.36; 0.10.00
Determined values (%) 613.82; H 4.56; N15.84; F5.30; Cl 9.87.
- 58 - i /
PREPARATION OF COMPOUND 64 <X .- (2-chloro-6-fluorophenyl) - <X. - / 2- (4-chlorophenyl) ethyl / -1,2,4-triazolo-1-propanenitrile
Step 1 - Preparation of X- / 2- (4-chlorophenyl) ethyl / 2-chloro-6-fluorophenylacetonitrile.
In a 200 ml, three neck round bottom flask, 7.5 grams of NaH a was charged. 60% (0.187 mole, 1.5 equivalents), washed three times with 25 ml hexane in 60 ml toluene: DMF 2; 1. To this solution was added dropwise over 0.5 hours 21.2 grams (0.125 mol, 1.0 equivalent) of 2-chloro-6-fluorophenylacetonitrile in 40 ml of toluene: D? ÍF, 2: 1. The reaction mixture was stirred for twenty minutes at. 10 ° C and then at room temperature for one hour after which time 32.1 grams of 2- (4-chlorophenyl) ethyl methanesulfonate (0.137 mol, 1.1 equivalents) was added dropwise. in 60 ml of toluene: DMF, in the proportion of 2? 1. Approximately 70 ml of 2: 1 toluene: DMF was added and the reaction mixture was stirred for a further 3.5 hours, after which gas-liquid chromatography indicated that the reaction was complete. 50 ml of water were then added followed by 10 ml of 10% HCl and 300 ml of ether. The ether was washed with water (100 ml) and extracted twice with ether (50 ml) and then washed with water. The combined ethereal solutions were dried and concentrated to give 40.0 grams of crude product, which was distilled off under reduced pressure. Obtained
26.6 grams (69.8%) of product having a boiling point of 175 ° - 185 ° C at 1 mm Hg.
Nuclear magnetic resonance spectrum (90 ί., Ήζ):
(2.2 - 2.9 (m, 4H), 4.2 - 4.4 (t, 1H) and 7.0 - 7.4 (6n, 7H).
Step 2 - 1-Bromo-2-cyano-2- (2-chloro-6-fluorophenyl) -4- (4-chlorophenyl) butane
In a 200 ml three neck round bottom flask was charged 2.4 grams of 60% NaH (0.048 mol, 1.2 equivalents), washed twice with 25 ml hexane in 40 ml. from DI.T. At room temperature, 12.28 grams (0.04 mole, 1.0 equivalent) of X- / 2- (4-chlorOphenyl) ethyl] -2-chlorohydrochloride was added dropwise over 0.5 hours at room temperature. 6-Fluorphenyl acetonitrile in 30 ml of Di-IF. Then, 10.43 grams of CHgBrg (0.60 mole, 1.5 equivalents) in 20 ml DLIP was added dropwise and the reaction mixture was stirred at room temperature for 0.5 hours, then than gas-liquid chromatography indicated that the reaction was complete. The reaction mixture was cooled after one hour by adding 20 ml of water and 200 ml of separated ether. After washing with water, drying and concentrating, 14.84 grams (92.9% yield) were obtained and used directly in the coupling reaction with triazole.
Nuclear magnetic resonance spectrum (90 i-Hz) 5
S 2.4 - 2.8 (m, 4H), 3.8 - 4.2 (ABq, 2H) and 6.9 - 7.3 (m, 7H).
/
- 60 -(
.......
ί.<sup>1</sup>¾
Step 3 - Preparation of N - (2-Chloro-6-fluorophenyl) -7- / 2- (4-chlorophenyl) -et11 / -1,2,4-triazol-1-propanenitrile.
In a one-neck 200 ml round bottom flask, 14.84 grams (0.03θ mole, 1.0 equivalent) of 1-bromo-2-cyano-2- (2-chloro-6-fluorophenyl) was charged. ) -4- (4-chlorophenyl) butane in 50 ml B.-SO. To the reaction mixture was added 4.89 grams (0.0457 mole) of triazole potassium salt in 30 ml of D<sup>T</sup>SO and the flask was heated to 120 ° C. After
1.5 hours at 120 ° C, gas-liquid chromatography indicated that the reaction was complete and quenched by cooling to room temperature and adding 50 ml of water and 250 ml of ethyl acetate. After separation, the organic phase was washed twice with 100 ml of water, concentrated and triturated with ether. The solid was filtered and the filtrate concentrated and triturated with ether. The additional solid was filtered and a total of 8.06 grams was obtained, mp 98 ° - 99 ° C (54.6% yield).
Infrared Electro (nujol, cm ")
I
3020 (m), 1600 (s), 1570 (m), 1500 (s), 1450 (s), 1275 (s), 1240 (m), 1205 (m), 1135 (m), 910 (m), 890 (s) and 790 (s).
Nuclear magnetic resonance spectrum (90 1Hz):
S 2.4 - 3.2 (m, 4H), 4.8 - 5.2 (ABq, 2H),
6.9 - 7.4 (m, 7H), 7.9 (s, 1H) and
8.2 (s, 1H).
Elemental analysis ΐ ^ 19 ^ 15 ^ 4 ^^ 2
<img file="PT85239B_D0063.tif" />
Theoretical values ($);
C 58.60; H 3.89; N 14.40; F 4.88; Cl 18.22
Determined Amounts ($):
C 58.43; H 3.91; N 14.43; F 4.78; Cl 17.89
FIRST PREPARATION 74
X.-Z-2- (4-bromophenyl) ethyl7- (2-ethoxyphenyl) -1,2,4-triazolo-1-propanenitrile
Step 1 - Preparation of 2- [2- (4-Bromophenyl) ethyl] -2-2-ethoxyphenyl acetonitrile.
5.6 grams of 60% NaH (0.14 mol, 1.4 equivalents), washed three times with 25 ml of hexane, was charged to a four-neck, 1-neck round bottom flask with 25 ml of hexane. 100 ml of 2: 1 tolueneifDUF. Then 16.1 grams (0.10 mole, 1.0 equivalent) of 2-ethoxybenzyl cyanide in 200 ml of toluene: DMF were added. 2 ? 1 and stirred at room temperature for two hours. After this time, 5.7 grams of KH (0.05 mole, 0.5 equivalent) washed with 25 ml of hexane in 50 ml of toluene: DMF was added in a 2: 1 ratio. At this time, 31 grams (0.11 mol, 1.1 equivalents) of 4-bromophenethyl methanesulfonate in 100 ml of toluene, DMF, in a ratio of 2 · 1, were added dropwise over ten minutes. The reaction mixture was stirred overnight at room temperature. The reaction mixture was 81% monoalkylated product as indicated by gas-liquid chromatography. The reaction was quenched with 10% HCl and 400 ml of ether was added and washed four times with 150 ml of water. The dissolution was dried and magnesium sulfate, then concentrated to give 7%.<sup>r <u, aB</sup> € ƒâ € ƒâ € ƒOrange orange oil in a solid was filtered off and filtered and washed with cold toluene. 14.8 grams of a white solid * (43.7% yield) was obtained.
nuclear magnetic resonance imaging (90 MHz):
<sup>!</sup>gi
Ρ:
1.3 - 1.5 (*, 3H), 2.0 - 2.3 (m, 2H),
2.2 - 2.9 (?, 2H), 3.9 - 4.2 (m, 3H), and 6.8 - 7.5 (m, 8H).
- Preparation of 1-Bromo-2-cyano-2- (2-ethoxyphenyl) -4- (4-bromophenyl) butane
77 'W
In a 500 ml, three necked round bottom flask, 3.5 grams of 100% KH (0.087 mole, 2.0 equivalents), washed twice with 25 ml of hexane in 25 ml ml of DMF. At room temperature> 2 ° C, 14.8 grams (0.044 mole of (- / 2- (4-bromophenyl) ethyl / 2'-ethoxyphenyl acetonitrile) in 60 ml was added dropwise. DMF. After one hour, CHgBrg (0.066 mole, 1.5 equivalents) in 40 ml was added dropwise to the exothermic reaction. The temperature was raised to 45 ° C. It was stirred at room temperature for three hours.
Íg |, ....................
after which gas-liquid chromatography indicated that reI η / · · 2 | ·.
was 85% complete. The reaction mixture was stirred.
Ι ^ Ιΐ, ΙΙί ^ νη 85% complete. The reaction mixture was stirred overnight at room temperature and 0.8 to 100% (0.022 mole, 0.5 equivalent) in 20 ml was added.<sup>;</sup>||| ^ · \: ^ <ηίάθ8 per 1.2 grams of CH<sub>2</sub>Br<sub>2</sub> in 5 ml DMP.
<img file="PT85239B_D0064.tif" />
<img file="PT85239B_D0065.tif" />
After one hour, the reaction was complete. The reaction was quenched by adding 75 ml 10% HCl followed by the addition of 300 ml ether. After washing with 4.100 ml of water, the product was dried and removed by rotary evaporation. 18.3 yellow-orange oil (96.8% yield) was obtained.
: <1;
1 'times with the dissolrams of
Nuclear magnetic resonance Bspeetro. (60 MHz):
1.3 - 1.6 (t, 3H), 2.2 - 2.8 (', 4H),
3.7 - 4.2 (δ, 4H) and 6.8 - 7.6 (δ, 8h).
J - Preparation of (N - (4-bromophenyl) ethyl) - [α-2-ethoxyphenyl) - * 1,2<sub>f</sub>4-triazolo-1-propanenitrile.
1|·|
In a 300 ml three neck round bottom flask was charged 18.3 grams of 1-bromo-2-cyano-2- (2-ethoxyphenyl) -4- (4-bromophenyl) butane (0, 43 mol, 1.0 equivalent) in 100 ml DMSO. The reaction mixture was added at room temperature with 5.4 grams of trlazole potassium salt (0.050 mol) and the reaction mixture was stirred at 100 ° C for twenty hours. Gas-liquid chromatography indicated that the reaction was complete and the reaction was quenched by adding 10% HCl and ether. 0 The product was crystallized out during extraction and the volume of solvent was reduced and the product was filtered off. 11.3 grams · was isolated. - '.! | it of a light brown solid with a melting point of 130 ° f ··
132 ° C (63% yield).
| l |
Infrared Spectrum (nujol, cm<sup>-1</sup>) :
1590 (w), 1265 (m), 1245 (m), (1135 (m), 1030 () and 750 (m).
- 64 .....
/ μ Nuclear magnetic resonance spectrum (60 MHz) t
1.4 - 1.6 (t, 3H), 1.9 - 2.9 (m, 4H),
4.0 - 4.4 (q, 2H), 4.9 (s, 2H), 6.8 - 7.4 (m, 8H) and 7.8 (s, 2H).
Elemental Analysis
N ^ BrO
Theoretical Values ($):
C 59.28; H 4.98; N 13.18; 0 3.76; Br 13.80.
Determined Amounts ($):
C 59.42; H 5.06; N 13.12; 0 3.99; Br 18.60.
COCKTAIL PREPARATION 83
- / 2- (3-Fluorphenyl) ethyl-7-phenyl-1,2,4-triazolo-1-propanitrile
Step 1 - 1- (Hydroxymethyl) -1,2,4-triazole pre-preparation.
In a 500 ml three neck round bottom flask equipped with condenser and mechanical stirrer, 69.1 grams of triazole (1 mole), 30.1 grams of paraformaldehyde and 1 ml of triethylamine in 250 ml of THF were charged. . The reaction mixture was stirred under refluxing nitrogen for eighteen hours, after which time the mixture was concentrated by rotary evaporation. A white solid was obtained which was filtered off and washed with ether to give 96.8 grams of product (97.6% yield) with a melting point of 67 ° - 70 ° C. The product may be further purified by dissolving it in hot acetone, cooling to room temperature, filtering the solid and washing with ether.
<img file="PT85239B_D0066.tif" />
? asc 2 - Preparation of 1- (chloromethyl) -1,2,1-triazole hydrochloride
In a 1-neck, four-necked flask equipped with condenser, hopper and mechanical stirrer, 45 1- (hydroxymethyl) -1,2,4-triazole (0.464 mole) pellets were loaded in 500 ml THP and it was heated to 40 ° C with vigorous stirring. Then SOG1 was added dropwise<sub>2 </sub>(61 ml, 0.84 mol) while maintaining the temperature at 45 ° C. During the addition, a precipitate formed and the mixture was stirred for a further two hours. The product was filtered, washed three times with ethyl acetate and dried in vacuo at room temperature. 67.3 grams of product with a melting point of 118-130 ° C (94.2% yield) were obtained.
Step 3 - Preparation of 2- (3-chlorophenyl) -ethanol. S-Fluorphenylacetic acid reduction with diborane.
In a 2-neck, four-necked flask equipped with condenser and funnel under a nitrogen atmosphere, 75 grams of 3-fluorophenylacetic acid (0.48 mole) was charged in 100 ml of THE. Then, 500 ml of a 1 molar diborane-THP (0.50 mole) complex was added dropwise. After the addition, gases were released and the reaction mixture was cooled to maintain a temperature below 10 ° C. After the addition was complete, the reaction mixture was stirred at room temperature until thin layer chromatography was found to be complete. The reaction was quenched by adding ice and water, the product was extracted with ether and washed with 5% NaOH, 5% HCl and water and dried over magnesium sulfate.
really. After concentrating, 77.3 grams of a brown oil were obtained.
Nuclear magnetic resonance spectrum (R) (90 MHz):
Δ 2.6 (2, 1H), 2.7 - 2.9 (t, 2H),
3.7 - 3.9 (t, 2H) and 6.9 - 7.4 (m, 4H).
Step 4 - 2- (3-Fluorphenyl) -ethylchloride braking. 2- (3-Fluorphenyl) -ethanol chlorination.
In a 500 ml four neck round bottom flask equipped with a condenser and funnel, stirred under a nitrogen atmosphere, 14.0 grams of 2- (3-fluorophenyl) -ethanol (0.1 mol) was charged. 1.0 equivalent) in 60 ml of toluene. Then 22 ml SOC1 was added dropwise<sub>2</sub> (35.9 grams, 0.30 mole, 3.0 equivalents) while holding? temperature below 15 ° C with external cooling. Pyridine (8.7 grams, 1.1 equivalents) in 10 ml of toluene was added dropwise. The reaction mixture was stirred overnight at room temperature, whereupon chromatography. A thin layer indicated that the reaction was complete. The reaction mixture was concentrated and the pipeline was isolated after water was added, extracted with ether and washed with water. After drying and concentrating, 10.2 grams of an orange oil (64.5% yield) was obtained.
Nuclear magnetic resonance spectrum (60 I.lHz)
2.9 - 3.2 (m, 2H), 3.5 - 3.8 (m, 2H) and 6.8 - 7.4 (m, 4H).
/
Step 5 - X - / 2- (3-Fluorphenyl) ethyl / phenyl acetonitrile prenaration.
5.6 grams of 60% NaH (0.140 mole, 1.4 equivalents) was charged to a 1 liter three-neck round-bottomed flask, washed three times with 25 ml hexane in 100 ml of toluene: Di'F in a ratio of 2 · 1. Then 11.7 grams (0.10 mole, 1.0 equivalent) of benzyl cyanide in 150 ml of toluene: DMF was added in the proportion of 2; 1, and stirred for two hours. Then 2- (3-fluorophenyl) ethyl chloride (20 grams, 0.126 mole) in 100 ml of a 2 · 1 toluene · DMF mixture was added. The reaction was complete after three hours. hours and then quenched with 10 ml of 10% HCl. Water was added and extracted with 300 ml ether which was washed four times with 100 ml water then dried and concentrated. 22.5 grams of crude product was obtained, which was distilled off under reduced pressure. 11.2 grams of product were obtained, boiling at 160 ° - 163 ° C at 1 mm Hg (46.9% yield).
Nuclear magnetic resonance spectrum (90; δ) · δ 2.0 - 2.3 (m, 2H), 2.6 - 2.8 (m, 2H),
3.6 - 3.8 (t, 1H) and 6.8 - 7.5 (m, 9H).
Step 6 - Preparation of X - / 2- (3-Fluorphenyl) ethyl / - X-phenyl-1,2,4-triazolo-1-nropanenitrile.
In a 500 ml four neck round bottom flask, 0.3 gram of NaH a was charged. 60% (0.075 mol, 3.0 equivalents), washed twice with ml of hexane in 50 ml of DKF. To the reaction mixture, 6.0 grams of - / 2- (3-fluorophenyl) ethyl] was added dropwise.<sup>and</sup>nyl aeetonitrile (0.025 mol, 1.0 equivalent) in 200 ml D7F. After one hour, 6.0 grams of chloromethyltritzol.HCl (0.038 mol, 1.5 equivalents) were added directly in two portions. After one hour, the gas-liquid chromatography assay indicated that the reaction was incomplete and an additional 1.5 grams (1.5 equivalents) of 60% NaH was added to 25 ml of D ,F, then After washing with 25 ml hexane, the reaction was complete after one hour and then quenched by adding ether containing methanol. Then 25 ml of 10% HCl was added, followed by 300 ml of ether. This was followed by a four-time wash with water (150 ml). It was dried and concentrated to dryness to give 5 grams of a yellow oil. The desired product crystallized from ether and yielded 2.3 grams of pipeline with a melting point of 100 ° - 101 ° C (29% yield),
Infrared Spectrum (nujol, cm “<sup>x</sup>) :
158 ° (w), 1265 (m) and 1140 (m).
Nuclear magnetic resonance spectrum (90 1 Hz)
Elemental Analysis: <sup>Ç</sup>19<sup>H</sup>17<sup>N</sup>4<sup>P</sup>
Theoretical values ($): C 71.21; H 5.35; N 5.94;
17,50
Determined values ($): C 71.20; H 5.36; N 5.93; F 17.44.
<img file="PT85239B_D0067.tif" />
— 69
- / 2- (3-bromophenyl) -6Ϊΐ17 · ~ - (2-ethoxyphenyl) -1,2,4-triazole COMPOSITE PREPARATION
-1-propanenitrile
Step 1 - Preparation of 2- (3-bromophenyl) ethanol. Writing 3-bromophenyl-acetic acid with diborane.
In a 2-liter four-necked flask under agitation and under a nitrogen atmosphere, equipped with condenser and funnel, 75 grams of 3-bromophenylacetic acid (0.34 mole) was introduced into 100 ml of THF. . Then, 350 ml of 1 molar diborane-THF complex (0.35 mol) was added dropwise. After addition, a gas was released and the reaction mixture was cooled to maintain a temperature below 10 ° C. After the addition was complete, the reaction mixture was stirred at room temperature until the reaction was complete by thin layer chromatography. The reaction mixture was cooled by adding water and ice and the product was extracted with ether and then washed with 5% NaOH, 5% HCl and water. Dried over magnesium sulfate. After concentrating, 77.4 were obtained. grams of product and chlorinated directly.
Nuclear magnetic resonance spectrum (90 Nfz):
2.7 - 2.9 (α, 3D), 3.7 - 3.9 (t, 2H) and 7.1 - 7.4 (λ, 4H).
Step 2 - Preparation of 2- (3-bromophenyl) ethyl chloride. Chlorination of 2- (3-bromophenyl) ethanol.
In a 500 ml three-neck round-bottom flask equipped with a condenser and a funnel,
- 70 / /
Under stirring and under a nitrogen atmosphere, 20.0 grams of 2- (3-bromophenyl) -ethanol (0.1 mol, 1.0 equivalent) was charged in 60 ml of toluene. Then it was added dropwise. 22 ml SOClg (35.9 grams, 0.30 mole, 3.0 equivalents) while maintaining the temperature below 15 ° C with external cooling. Pyridine (8.7 grams, 1.1 equivalents) in 10 ml of toluene was added dropwise. The reaction mixture was stirred overnight at room temperature, after which time thin layer chromatography indicated that the reaction was complete. The mixture was concentrated and the product was isolated after adding water, extracting with ether and washing with water. After drying and concentrating, 14.2 grams of an orange oil (64.2% yield) was obtained.
Nuclear magnetic resonance electron (60 MHz)?
S 2, J = 3.1 (m, 2H), 3.5 - 3.8 (m, 2H) and 7.0 - 7.3 (m, 4H).
Step 3 - Preparation of tα- / 2- (3-Bromophenyl) ethyl / -2-ethoxyphenyl acetonitrile.
To a 1 liter four-neck round-bottomed flask, 3.5 grams of 60% NsII (0.083 mole, 1.4 equivalents), washed three times with 25 ml of hexane, was added to the flask. 100 ml of toluene? 2: 1 BMF. Then 9.5 grams (0.059 mole, 1.0 equivalent) of 2-ethoxybenzyl cyanide in 200 ml of toluene: DMF was added at 2 r 1 and stirred. for two hours. Then 2- (3-bromophenyl) ethyl chloride (13 grams, 0.059 mol) in 100 ml of toluene was added.
<img file="PT85239B_D0068.tif" />
DMF, 2: 1 ratio. After twenty hours, the reaction was incomplete and 2.0 grams of 100% KH (0.05 mole) in 25 ml DI was added.<sup>, T</sup>F. After four hours, the reaction was complete and then quenched with 10% HCl, extracted with ether, washed with water, dried and concentrated to 20 grams of an oil. crude (97% pure). The product was distilled off under reduced pressure and 12.3 grams of product were obtained, boiling 195 ° - 210 ° C at 1 mm Hg (58.9% yield).
Nuclear magnetic resonance spectrum (90 MHz)?
1.2-2.4 (t, 3H), 2.0-2.3 (t, 2H),
2.6 - 2.9 (t, 2H), 3.8 - 4.2 (m, 3H) and 6.7 - 7.4 (m, OH).
Stage 4 - Â · - / 2- (3-Bromophenyl) ethyl / - (2-ethoxyphenyl) -1,2,4-triazole-1-ronanenitrile.
In a 500 ml four neck round bottom flask, 2.8 grams of 100% KH (0.07 mole, 3.0 equivalents), washed twice with 25 ml of hexane, was charged with 50 ml D ·! ·<sup>1</sup>. To the reaction mixture was added dropwise 3.0 grams of <= is - / 2- (3-bromophenyl) ethyl / -2-ethoxyphenyl acetonitrile (0.023 mol, 1.0 equivalent) in 100 ml of DMF. After one hour, 5.7 grams of chloromethyltriazole.HCl (0.037 mol, 1.6 equivalents) were added directly in two portions. After one hour, gas-liquid chromatography indicated the reaction was incomplete and an additional 2.8 grams (3.0 equivalents) of KH was added, followed by 1.8 grams (0.5 equivalent) of chloromethyltriazole. After stirring overnight the temnera
-72-, τ
Hey
X., _______ -. At room temperature, the reaction was complete and was quenched by the addition of a small amount of MeOH in 100 mL of ether, followed by the addition of 10% HCl (10 mL). Then 200 ml of ether was added, then washed four times with 100 ml of water, dried and concentrated to give 7 grams of a crude oil. The product was purified by flash chromatography with ethyl acetate? hexane in a 1: 1 ratio and 2.3 grams (24% yield) of a viscous oil were obtained.
Nuclear magnetic resonance spectrum (60 MHz) ·
1.4 - 1.7 (t, 3H), 2.1 - 3.0 (m, 4H),
4.0 - 4.3 (m, 2H), 5.0 (s, 2H), 6.9 - 7.4 (m, 8H) and 7.8 (s, 2H).
<td>Analyze</td><td>elementary f θ21 ^ 21 ^ 4®<sup>Γ</sup>θ</td>
<td>Values</td><td>theoretical ($);</td>
<td>Ç</td><td>59.28; H 4.98; N 13.18; 0 3.76; Br 18.80</td>
<td>Values</td><td>determined (%)</td>
<td>Ç</td><td>58.40; H 5.43; N 11.56; 0 6.30; Br 17.69</td>
PREPARATION OF THE COMPOUND 93 c- [2- (4-methoxyphenyl) ethyl] phenyl-1,2,4-triazolo-1-propanenitrile
Step 1 - Preparation of = - - / 2- (4-Methoxyphenyl) ethyl / phenylacetonitrile.
In a 2-neck four-neck round bottom flask equipped with a thermometer,
7-% /
7<sup>?</sup> > charge and mechanical stirrer, 117 grams (1.0 mole, 2.0 equivalents) of benzyl cyanide and 115 grams (0.5 mole, 1.0 equivalent) of 2- (4-methoxyphenyl) methanesulfonate were introduced. -ethyl in 400 ml DMSO and 200 ml toluene. The reaction mixture was cooled to 10 ° C and 5 grams (0.63 mole, 0.63 mol) was added dropwise over thirty minutes.
1.2 equivalents) 50% NaOH. Is the reaction exothermic? the temperature rose to 35 ° C and then the reaction mixture was cooled to 10 ° C. The reaction mixture was stirred at room temperature for forty eight hours and gas-liquid chromatography indicated 60% product and 40% benzyl cyanide. The reaction was quenched by adding 2 liters of water and then extracted twice with ether (1 liter), washed twice with water (1 liter) and brine (1 liter). Drying over MgSO4 and concentration afforded 171 grams of a crude oil (67% product). The product was distilled under vacuum and 104 grams of a yellow oil (82.5% yield based on mesylate) was obtained which had a boiling point of 165 ° - 170 ° C at 2 mm Hg.
Nuclear magnetic resonance spectrum (60 MHz) · & 1.9 - 2.4 (m, 2H), 2.5 - 2.7 (m, 2H),
3.7 (s, 4H), 6.8 - 7.2 (ABq, 4H) and
7.5 (s, 5K).
Step 2 - Preparation of 1-Bromo-2-cyano-2-phenyl-4- (4-methoxyphenyl) butane.
In a 1-liter four-neck round bottom flask, 100 grams (0.40 mole,
- 1.0 equivalent) of X- / 2- (4-methoxyphenyl) ethyl / phenyl acetonitrile and 139.1 grams of dibromomethane in 200 ml DMSO. To the reaction mixture was added dropwise 79.6 grams of 50% NaOH (0.99 mole, 2.5 equivalents) over fifteen minutes. The reaction was exothermic and the reaction mixture warmed to 95 ° C. It was then cooled to 50 ° C and stirred for one hour at 50 ° C. Gas-liquid chromatography assay indicated that the reaction was complete. The reaction mixture was poured into 2 liters of water, extracted by three. times with ether (500 ml), washed with water (1 liter) and brine and dried over magnesium sulfate. Obtained
130 grams (94% yield) of product as an amber oil after concentrating. The product was directly used in the coupling reaction with 0 triazole.
Nuclear magnetic resonance spectrum (60 THz): δ 2.4 - 2.8 (m, 4H), 3.7 (s, 2H), 3.8 (s, 3H),
6.8 - 7.3 (ABq, 4H) and 7.5 - 7.8 (br s, 5H).
>
Step 3 - Preparation of X- / 2- (4-Methoxyphenyl) ethyl / ““
-phenyl-1,2,4-triazolo-1-propanenitrile.
In a 1 liter three necked flask, 57 grams of triazole (0.74 mole, 2.0 equivalents) was charged in 300 ml D?<sup>r</sup>SO and 102 grams of KgCO3 (0.74 mole, 4.0 equivalents). The reaction mixture was stirred at 135 ° C for one hour, after which 127 grams of 1-bromo-2-cyano-2-phenyl-4- (4-methoxyphenyl) butane (0.37 mol, 1 ml) was added. , 0 equivalent) in 200 ml DMSO. The temperature dropped to 115 ° C and was heated to 135 ° C for two hours and then at 80 ° C for eighteen hours. The reaction mixture was discarded in water (3 liters), extracted five times with ethyl acetate (500 ml), washed twice with water (500 ml) and brine (500 ml). After drying over magnesium sulfate, it was filtered and concentrated. A yellow oil was obtained which was suspended in hexane. A yellow solid was filtered which was filtered with 10% diethyl ether / 90% hexane. Drying gave 95 grams of a product with the melting point of 91-9A ° C (77.4% yield).
Nuclear magnetic resonance electron (60 Ι, Ήζ) í
<td></td><td>δ 2.4-2.9 (m, HA), 3.9 (s, 3H), 5.1 (s, 2H), 6.8 - 7.4 (ABq, 4H), 7.7 - 7.9 (broad s, 57), 8.2 (s, 1H) and 8.4 (s, 1H).</td>
<td>Analyze</td><td>elementary * <sup>Ç</sup>20<sup>H</sup>20<sup>N</sup>4°</td>
<td>Values</td><td>theoretical (%)?</td>
<td>Ç</td><td>72.24; H 6.06; N 16.87; 0 4.32.</td>
<td>Values</td><td>determined (/):</td>
<td>Ç</td><td>72.55; H 6.39; N 16.09; 0 5.21.</td>
The compounds prepared from. In accordance with the present invention, they have been tested for their activity against a number of plant diseases. Test compounds were dissolved in acetone, methanol and water to form a series of dilutions from 300 µm to 5 µm. Depending on the time the assays were performed, various dilution series were used, for example 300, 75, 19, 5 or 100, 25, 6. Unless otherwise indicated, the plants were sprayed until
1 .. ya run off with a mechanical spray on the same day or the day before inoculation. The test protocol for wheat stem rust (WSR), wheat leaf rust (WLR), wheat powdery mildew (Λ ;. :) and rice rust (RB) were as follows:
CAUIE RUST DO .. WHEAT ÇTSR) - Puccina gra minis
Cultivate TYLER wheat seedlings were grown on ready-made soil and used to study the active compounds about seven days after sowing. Wheat plants were fertilized with LIQUID-T fertilizer prior to use to maintain vigorous plants throughout the test period.
Depending on the time the assay was performed, one of three methods was used to prepare urediospore suspensions.
K Water Atomizer / Devilbiss
A <7SR spore suspension was prepared by harvesting infected leaves from three to four week old crop plants and vigorously shaking the leaves with water containing the TWEEN 80 surfactant. The spore suspension was filtered through a cloth. large meshes to separate the debris and adjusted to three to five spores by a wide square on a hemocytometer. Plants were inoculated using a Pevilbiss atomizer. While the plants were still damp, they placed themselves in a damp cabin.
2. Qleo / Devilbiss Atomizer
Suspension of ffSR spores in oil was preferred by harvesting fresh spores from two to three week infected plants, a vacuum pump or a rust collector or dehydrating frozen spores (deep freezing) and addition to SOLTROL spray oil. , with a concentration of 5 ng spores per 1 ml of oil. Plants were inoculated with a Devilbiss atomizer by passing over the plants on all sides. The plants were allowed to dry for about twenty minutes and then placed in a humidity cabinet.
3 Special small oil atomizer
The spore suspension was preferred as described in method number 2, except that 4 mg of spores per 1 ml of oil was used. The inoculum was then distributed into gelatin capsules and applied with a vacuum pump. Four passages were made on both sides of the plant for the sake of uniformity. The plants were allowed to dry for about twenty minutes and then placed in a humidity cabinet.
The humidity cabinet provided 100% free water and was maintained at a constant temperature of 21.1 ° C (70 ° F). Inoculated plants were subjected to twelve hours of darkness, followed by three to four hours of fluorescent light. The plants were then transferred to a greenhouse and analyzed for thirteen days.
<img file="PT85239B_D0069.tif" />
- 78 WHEEL LEAF RUST (MLR) - Puccina recondita
For the ZLR assay the same procedure was used as for WSR, except that light exposure was not used in the WLR case.
PULVERULENT WHEAT MEDIUM (.YPN) - Erysiihe graminis
Wheat seedlings were developed to cultivate VICTORY 283 ftm ready earth. Plants were six to seven days old and were fertilized with LIQUID-M fertilizer prior to testing to promote vigorous development during the testing period.
The plants were inoculated by fanning sporulating crop plants on them, spreading the mildew spores. The inoculated plants were placed on sub-irrigation trays in a temperature controlled room providing a temperature of 21.1 ° C (70 ° F) for disease development.
As the development of ATL · · is greatly affected by the presence of volatile chemical products, the vessels were as far apart as possible and the trays separated by dose by elastic sheets. Disease development was rated seven to ten days after inoculation on a percentage basis relative to control.
RICE RICE (RB) - Piricularia or ^ zas
Rice plants of the cultivar M-201 were grown in a 5 cm (2 oolegaclas) glass greenhouse at 20-30 ° C containing unsterilized soil / peat / fertilizer for fourteen days. Rice plants were not cut down before being used
The inoculum was produced in vitro on nutritive agar (50 grams Gerber oatmeal, 20 grams bacto agar, 10 grams dextrose bacto, 100 ml deionized water). The plates were inoculated with a mycelium (aged 7 - 14 days) from Piricularia oryzae. In the transfer, the outer margin of the dark region was used. Inoculated plates were kept at room temperature under constant fluorescent light.
P. oryzae plates aged 10 - 14 days were dipped in a solution containing 0.25 g of sodium oleate, 2 grams of gelatin and 1000 ml of deionized water. The plates were scraped with rubber police to release the conidia, filtered through a double layer of wide mesh fabric and the suspension adjusted to 25,000 - 30,000 spores / ml using a hemacytometer.
Suspensions on opposite sides of a dune row of rice plants were sprayed using a hand sprayer. Sufficient inoculum has been blended to achieve even distribution from the ground to the mat of the rice leaves on opposite sides of the pot (approximately 50 ml / 50 pots). The hand spray was shaken after each pass to preserve the suspension solution.
The inoculated plants were immediately placed in a humidity cabinet at 25 ° C for sixty-six hours before being placed in a greenhouse under a plastic tent. The plants were under-irrigated but not left in water for more than two hours. The plastic sides of the tent were lifted during working hours and closed at the end of the day.
After being maintained for seventy-six hours under greenhouse conditions, the plants used in the biological assay were observed and disease control was determined in percent (compared to the inoculated control).
The compounds were tested at different dosages, depending on when the assays were performed. Test results are shown in Table 6 for a dosage per compound. If the compound has been tested more than once at the stated dosage, the mean is given.
TABLE 6
FUNGICIDE ACTIVITY
Control Percentage at 300 opm
<td></td><td>WSR</td><td>.VLR</td><td>rfla ''</td><td>RB</td>
<td> 1</td><td> 100</td><td> 95</td><td> 99</td><td> 66</td>
<td> 2</td><td> 97</td><td> 100</td><td> 93</td><td> 83</td>
<td> 3</td><td> 100</td><td> 100</td><td> 99</td><td> 98</td>
<td> 4-</td><td> 100</td><td> 100</td><td> 100</td><td> 91</td>
<td> 5</td><td> 92</td><td> 80*</td><td> 99</td><td> 15</td>
<td> 6</td><td> 100</td><td> 100</td><td> 96</td><td> 12</td>
<td> 7</td><td> 100</td><td>9C *</td><td> 100</td><td> 88</td>
<td> 8</td><td> 100</td><td> 80*</td><td> 90</td><td> 95</td>
<td> 9</td><td> 100</td><td> 50»</td><td> 97</td><td> 50</td>
<td> 10</td><td> 100</td><td> 100»»</td><td> 98</td><td> 97</td>
<td> 11</td><td> 100</td><td> 100»»</td><td> 99</td><td> 100</td>
<td> 12</td><td> 100</td><td> 90»</td><td> 90</td><td> 88</td>
- 61 Percent Control at 300 ppm
<td></td><td>7 / SR</td><td>> / LR</td><td>.tlV</td><td>RB</td>
<td> 13</td><td> 94</td><td> 90*</td><td> 99</td><td></td>
<td> 14</td><td> 100</td><td> 95*</td><td> 100</td><td> 10</td>
<td> 15</td><td> 92</td><td> 50*</td><td> 70</td><td>uO</td>
<td> 16</td><td> 100</td><td> 100**</td><td> 99</td><td> 100</td>
<td> 17</td><td> 98</td><td> 80*</td><td> 100</td><td> 93</td>
<td> 18</td><td> 100</td><td> 95*</td><td> 100</td><td> 100</td>
<td> 19</td><td> 99</td><td> 100**</td><td> 100</td><td> 97</td>
<td> 20</td><td> 95</td><td> 90*</td><td> 100</td><td> 35</td>
<td> 21</td><td> 100</td><td> 90*</td><td> 100</td><td> 63</td>
<td> 22</td><td> 100</td><td> —.</td><td> 100</td><td> 50</td>
»At 100 ppm
At 150 ppm
Control Percentage at 200 oom
<td></td><td>./SR</td><td>.VLR</td><td>• rtPi.</td><td>RB</td>
<td> 23</td><td> 100</td><td> 95*</td><td> 90</td><td></td>
<td> 24</td><td> 100</td><td> 100***</td><td> 100</td><td> 40**</td>
<td> 25</td><td> 100</td><td> 100***</td><td> 100</td><td> 50**</td>
<td> 26</td><td> 100</td><td> 100***</td><td> 90</td><td> 33**</td>
<td> 27</td><td> 100</td><td> —</td><td> 90</td><td> 100</td>
<td> 28</td><td> 100</td><td> —</td><td> 100</td><td> 0**</td>
<td> 29</td><td> 100</td><td> 95**</td><td> 100</td><td> 90**</td>
<td> 30</td><td> 100</td><td> 98***</td><td> 100</td><td> 60</td>
<td> 31</td><td> 100</td><td> 95*</td><td> 100</td><td> 0</td>
Control Percentage at 200 ppm
<td></td><td>WSR</td><td>WLR</td><td></td><td>RB</td>
<td> 32</td><td> 100</td><td></td><td> 100</td><td> 80</td>
<td> 33</td><td> 100</td><td> 91***</td><td> 100</td><td> 0</td>
<td> 34</td><td> 100</td><td> 80*</td><td> —</td><td> 100</td>
<td> 35</td><td> 100</td><td> —</td><td> —</td><td> 100</td>
<td> 36</td><td> 100</td><td> 80*</td><td> 100*</td><td> 87</td>
<td> 37</td><td> 100</td><td>yl</td><td> 100</td><td> 80</td>
<td>33</td><td> 100</td><td> 90*</td><td> 100</td><td> 0</td>
<td> 39</td><td> 100</td><td> 90*</td><td> 100</td><td> 0</td>
<td> 40</td><td> —</td><td> 100</td><td> 100</td><td> 80</td>
<td> 41</td><td> —</td><td> 100</td><td> 100</td><td> 0</td>
<td> 42</td><td> 99**</td><td> 95</td><td> 100</td><td> 0</td>
<td> 43</td><td> —</td><td> 100</td><td> 100</td><td> 0</td>
<td> 44</td><td> 100**</td><td> 99</td><td> 100</td><td> 95</td>
<td> 45</td><td> —</td><td> 99</td><td> 100</td><td> 50</td>
<td> 46</td><td> —‘</td><td> 75</td><td> 75</td><td> 50</td>
<td> 47</td><td> 100**</td><td> 75</td><td> 95</td><td> 50</td>
<td> 48</td><td> —</td><td> 75</td><td> 75</td><td> 0</td>
<td> 49</td><td> 100**</td><td> 95</td><td> 99</td><td> 0</td>
<td> 50</td><td> 100**</td><td> 75</td><td> 100</td><td> 0</td>
<td> 51</td><td> —</td><td> 75</td><td> 100</td><td> 50</td>
<td> 52</td><td> —</td><td> 50</td><td> —</td><td> 90</td>
<td> 53</td><td> —</td><td> 95</td><td> 95</td><td> 90</td>
<td> 54</td><td> —</td><td> 95</td><td> 95</td><td> 80</td>
<td> 55</td><td> —</td><td> 95</td><td> 100</td><td> 80</td>
<td> 56</td><td> —</td><td> 99</td><td> 99</td><td> 100</td>
<td> 57</td><td></td><td> 50</td><td> 50</td><td> 0</td>
- 83 χ Α 100 npm
At 150 ppm At 75 ppm.
100 pom Control P a rt
<td></td><td>WSR</td><td>WLR</td><td>WPIÍ</td><td>RB</td>
<td> 58</td><td> ——</td><td> 0</td><td> 75</td><td> 0</td>
<td> 59</td><td> —</td><td> 75</td><td> 95</td><td> 80</td>
<td> | 60</td><td> —</td><td> 0</td><td> 75</td><td> 0</td>
<td> 61</td><td> —</td><td> 0</td><td> 85</td><td> 40</td>
<td> 62</td><td> —</td><td> 75</td><td> 95</td><td> 0</td>
<td> 63</td><td> —</td><td> 50</td><td> 75</td><td> 0</td>
<td> 64</td><td> 100</td><td> 99</td><td> 87</td><td> 50</td>
<td> 65</td><td> 100</td><td> 95</td><td> 97</td><td> 90</td>
<td> 66</td><td> —</td><td> 75</td><td> 95</td><td> 90</td>
<td> 67</td><td> 95</td><td> 99</td><td> 85</td><td> 85</td>
<td> 68</td><td> 95</td><td> 95</td><td> 99</td><td> 85</td>
<td> 69</td><td> 100</td><td> 99</td><td> 100</td><td> 87</td>
<td> 70</td><td>MMK ·</td><td> 50</td><td> 95</td><td> 80</td>
<td> 71</td><td> 91</td><td> 50</td><td> 99</td><td> 90</td>
<td> 72</td><td> 97</td><td> 0</td><td> 97</td><td> 92</td>
<td> 73</td><td> —</td><td> 0</td><td> 85</td><td> 50</td>
<td> 74</td><td> 100</td><td> 92</td><td> 100</td><td> 0</td>
<td> 75</td><td> 100</td><td> 90</td><td> 100</td><td> 0</td>
<td> 76</td><td> 100</td><td> 95</td><td> 100</td><td> 0</td>
<td> 77</td><td> 100</td><td> 50</td><td> 98</td><td> 93</td>
<td> 78</td><td> 99</td><td> 75</td><td> 99</td><td> 100</td>
<td> 79</td><td> 95</td><td> 75</td><td> 85</td><td> 95</td>
Control Percentage at 100 ppm
<td></td><td>tfSR</td><td>WLR</td><td>WPtf</td><td>RB</td>
<td> 80</td><td> 100</td><td> 99</td><td> 99</td><td> 0</td>
<td> 81</td><td> 100</td><td> 75</td><td> 99</td><td> 0</td>
<td> 82</td><td> 100</td><td> 0</td><td> 95</td><td> 50</td>
<td> 83</td><td> —</td><td> 75</td><td> 99</td><td> 98</td>
<td> 84</td><td> 100</td><td> 99</td><td> 99</td><td> 90</td>
<td> 85</td><td> 100</td><td> 99</td><td> 97</td><td> 0</td>
<td> 86</td><td> 100</td><td> 90</td><td> 99</td><td> 85</td>
<td> 87</td><td> 100</td><td> 0</td><td> 100</td><td> 100</td>
<td> 88</td><td> —</td><td> 90</td><td> 95</td><td> 0</td>
<td> 89</td><td> 99</td><td> 75</td><td> 99</td><td> 40</td>
<td> 90</td><td> —</td><td> 95</td><td> 95</td><td> 0</td>
<td> 91</td><td> 100</td><td> 85</td><td> 95</td><td> 90</td>
<td> 92</td><td> —</td><td> 95</td><td> 99</td><td> 0</td>
<td> 93</td><td> 50</td><td> 0</td><td> 99</td><td> 100</td>
<td> 94</td><td> —</td><td> 50</td><td> 90</td><td> —</td>
<td> 95</td><td> 100</td><td> 97</td><td> 99</td><td> 95</td>
<td> 96</td><td> —</td><td> 95</td><td> 97</td><td> —</td>
<td> 97</td><td> 99</td><td> 5<sub>0</sub>**«*</td><td></td><td></td>
<td> 98</td><td> 99</td><td> 95</td><td></td><td> 90</td>
<td> **** ;</td><td>at 200 pom</td><td></td><td></td><td></td>
<td></td><td>3. 25 Pm,</td><td></td><td></td><td></td>
The compounds were tested at different dosages depending on the time the assays were performed. Test results for the best compounds that were tested are shown in Table 7 for three dosages. If the compound was tested at the same dose more than once, the mean value is given.
- 85 --
<img file="PT85239B_D0070.tif" />
TABLE 7
FUNGICIDE ACTIVITY
Wheat Stalk Rust
Compound / Dosage (in ppm)
<td></td><td> 300</td><td> 200</td><td> 100</td><td> 75</td><td> 33</td><td> 25</td><td> 6</td><td> 5</td>
<td> 1</td><td> 100</td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td> 98</td>
<td> 4</td><td> 100</td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td> 99</td>
<td> 6</td><td> 100</td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td> 100</td>
<td> 10</td><td> 100</td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td> 99</td>
<td> 16</td><td> 100</td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td> 99</td>
<td> 22</td><td> 100</td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td> 95</td>
<td> 23</td><td></td><td> 100</td><td></td><td></td><td> 100</td><td></td><td> 100</td><td></td>
<td> 24</td><td></td><td> 100</td><td></td><td></td><td> 100</td><td></td><td> 90</td><td></td>
<td> 25</td><td></td><td> 100</td><td></td><td></td><td> 100</td><td></td><td> 100</td><td></td>
<td> 26</td><td></td><td> 100</td><td></td><td></td><td> 100</td><td></td><td> 100</td><td></td>
<td> 27</td><td></td><td> 100</td><td></td><td></td><td> 100</td><td></td><td> 100</td><td></td>
<td> 33</td><td></td><td> 100</td><td></td><td></td><td> 100</td><td></td><td> 100</td><td></td>
<td> 37</td><td></td><td> 100</td><td></td><td></td><td> 100</td><td></td><td> 100</td><td></td>
<td> 78</td><td></td><td></td><td> 99</td><td></td><td></td><td> 100</td><td> 100</td><td></td>
<td> 85</td><td></td><td></td><td> 100</td><td></td><td></td><td> 100</td><td> 100</td><td></td>
<td> 86</td><td></td><td></td><td> 100</td><td></td><td></td><td> 100</td><td> 100</td><td></td>
<td> 95</td><td></td><td></td><td> 100</td><td></td><td></td><td> 100</td><td> 99</td><td></td>
<td> 98</td><td></td><td></td><td> 99</td><td></td><td></td><td> 99</td><td> 90</td><td></td>
<img file="PT85239B_D0071.tif" />
Wheat Leaf Rust
Compound / Dosage (in mn)
<td> 7</td><td> 150</td><td> 100 90</td><td> 75</td><td> 38</td><td> 25 80</td><td> 19</td><td> 6 80</td><td> 5</td>
<td> 10</td><td> 100</td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td> 96</td>
<td> 11</td><td> 100</td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td> 94</td>
<td> 12</td><td></td><td> 90</td><td></td><td></td><td> 95</td><td></td><td> 80</td><td></td>
<td> 16</td><td> 100</td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td> 100</td>
<td> 19</td><td> 100</td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td> 100</td>
<td> 21</td><td></td><td> 90</td><td></td><td></td><td> 80</td><td></td><td> 80</td><td></td>
<td> 23</td><td></td><td> 95</td><td></td><td></td><td> 90</td><td></td><td> 90</td><td></td>
<td> 24</td><td></td><td></td><td> 100</td><td></td><td></td><td> 99</td><td></td><td> 97</td>
<td> 25</td><td></td><td></td><td> 100</td><td></td><td></td><td> 99</td><td></td><td> 93</td>
<td> 26</td><td></td><td></td><td> 100</td><td></td><td></td><td> 99</td><td></td><td> 90</td>
<td> 28</td><td></td><td></td><td></td><td></td><td> 99(20)</td><td></td><td></td><td> 95</td>
<td> 41</td><td></td><td></td><td> 95</td><td></td><td></td><td> 97</td><td></td><td> 80</td>
<td> 49</td><td></td><td> 95</td><td></td><td></td><td> 95</td><td></td><td> 75</td><td></td>
<td> 69</td><td></td><td> 99</td><td></td><td></td><td> 95</td><td></td><td> 85</td><td></td>
<td> 80</td><td></td><td> 99</td><td></td><td></td><td> 97</td><td></td><td> 95</td><td></td>
<td> 98</td><td></td><td> 95</td><td></td><td></td><td> 90</td><td></td><td> 90</td><td></td>
<td colspan="2">0 Compound 28</td><td colspan="2">has been rehearsed</td><td>20 oom.</td><td></td><td></td><td></td><td></td>
<img file="PT85239B_D0072.tif" />
Pulverulent Wheat
Must / Dosing (in opm)
<td></td><td> 300</td><td> 200</td><td> 100</td><td> 50</td><td> 36</td><td> 33</td><td> 25</td><td> 12</td><td> 6</td><td> 5</td>
<td> 1</td><td> 99</td><td></td><td></td><td></td><td> 99</td><td></td><td></td><td></td><td></td><td> 98</td>
<td> 2</td><td> 100</td><td></td><td></td><td></td><td> 99</td><td></td><td></td><td></td><td></td><td> 98</td>
<td> 4</td><td> 100</td><td></td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td></td><td> 97</td>
<td> 10</td><td> 98</td><td></td><td></td><td></td><td> 97</td><td></td><td></td><td></td><td></td><td> 95</td>
<td> 19</td><td> 100</td><td></td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td></td><td> 96</td>
<td> 28</td><td></td><td> 100</td><td></td><td></td><td></td><td> 100</td><td></td><td></td><td> 90</td><td></td>
<td> 29</td><td></td><td> 100</td><td></td><td></td><td></td><td> 100</td><td></td><td></td><td> 95</td><td></td>
<td> 30</td><td></td><td> 100</td><td></td><td></td><td></td><td> 100</td><td></td><td></td><td> 100</td><td></td>
<td> 31</td><td></td><td> 100</td><td></td><td></td><td></td><td> 100</td><td></td><td></td><td> 95</td><td></td>
<td> 36</td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td> 100</td><td></td><td> 95</td><td></td>
<td> 41</td><td></td><td> 100</td><td></td><td></td><td></td><td> 95</td><td></td><td></td><td> 95</td><td></td>
<td> 49</td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td> 100</td><td></td><td> 75</td><td></td>
<td> 76</td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td> 99</td><td></td><td> 97</td><td></td>
<td> 81</td><td></td><td></td><td> 99</td><td></td><td></td><td></td><td> 92</td><td></td><td> 92</td><td></td>
<td> 82</td><td></td><td></td><td> 95</td><td></td><td></td><td></td><td> 97</td><td></td><td> 90</td><td></td>
<td> 83</td><td></td><td></td><td> 99</td><td></td><td></td><td></td><td> 97</td><td></td><td> 97</td><td></td>
<td> 85</td><td></td><td></td><td> 97</td><td></td><td></td><td></td><td> 95</td><td></td><td> 95</td><td></td>
<td> 86</td><td></td><td></td><td> 99</td><td></td><td></td><td></td><td> 99</td><td></td><td> 96</td><td></td>
<td> 87</td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td> 95</td><td></td><td> 97</td><td></td>
<td> 88</td><td></td><td></td><td> 95</td><td></td><td></td><td></td><td> 95</td><td></td><td> 95</td><td></td>
<td> 94</td><td></td><td></td><td> 90</td><td></td><td></td><td></td><td> 95</td><td></td><td> 90</td><td></td>
<td> 95</td><td></td><td></td><td> 99</td><td></td><td></td><td></td><td> 94</td><td></td><td> 96</td><td></td>
<td> 97</td><td></td><td> 100</td><td></td><td> 99</td><td></td><td></td><td></td><td> 100</td><td></td><td></td>
<td> 98</td><td></td><td></td><td></td><td></td><td></td><td></td><td> 99</td><td></td><td> 95</td><td></td>
<td colspan="2">Rust</td><td>of rice</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>
<td colspan="3">Compound / Dosage</td><td>(in !</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>
<td></td><td> 300</td><td> 200</td><td> 100</td><td> 75</td><td> 50</td><td> 25</td><td> 12</td><td> 6</td><td> 5</td><td></td>
<td> 7</td><td> 88</td><td></td><td></td><td> 85</td><td></td><td></td><td></td><td></td><td> 30</td><td></td>
<td> 17</td><td> 93</td><td></td><td></td><td> 99</td><td></td><td></td><td></td><td></td><td> 78</td><td></td>
<td> 18</td><td> 100</td><td></td><td></td><td> 100</td><td></td><td></td><td></td><td></td><td> 85</td><td></td>
<td> 97</td><td></td><td> 99</td><td></td><td></td><td> 90</td><td></td><td> 0</td><td></td><td></td><td></td>
<td> 98</td><td></td><td></td><td> 90</td><td></td><td></td><td> 90</td><td></td><td> 75</td><td></td><td></td>
- doh '/ w
The activity of a number of astes prepared according to. The present invention was tested against Cercosgora peanut (PC) plants, against Helminthosporium on peanut plants. barley (B'í) and against Septoris nodorum in wheat (SNW). The procedure used in these tests was as follows:
PURSUANT DQ PEANUT OR SNACK OF EARLY LEAVES. DO WDOIM (PC) - Cercos poro ara.chidicola
Cercospora arahidicola was grown on peanut and oatmeal agar (POA) in petri dishes for fourteen days under fluorescent light that was placed 20 cm above the cultures. Petri dishes were inoculated with 0.5 ml of a spore suspension prepared in sterile water containing a few drops of Twenn 80. The spore suspension was then spread over the surface of the placa plate by means of a sterile glass rod with the tip folded and spread to the shape of a hockey stick. Plate spores were harvested by adding deionized water containing a small amount of Tween 80 to the POA plates. The agar surface was scratched with a rubber policeman or similar object. The spore suspension was filtered through a wide mesh cloth to separate mycelium and agar fragments and then adjusted to a concentration of 2-4 x 1010 spores per ml.
Fourteen day old peanut plants of TAMNUT 74 were inoculated by spraying the leaves with inoculum until one formed. Uniform inoculum film ο π over the plant. Inoculated plants were incubated in a humid environment at 29.5 ° - 32.2 ° G (85 - 90 ° F) for seventy two hours. Plants were removed from the humid environment, allowed to dry and placed in a greenhouse. Comparisons of treatment results were made 10 - 14 days after inoculation.
HELALNTHOSPORIlTl OF THE BARLE OR TEST OF THE BARLE ANCHES (BH) - Helminthosoorium sativum
Barley plants of the variety
HENREY at the age of seven days growing in 5 cm (2 ”) pots twenty four hours prior to application of chemicals to achieve uniform plant height and to facilitate uniform inoculation. The plants were sprayed with the test compound or intermediate from a nesting tower (1.1 ml at the desired concentration per spray). The spray liquid was allowed to settle on the tower for one minute before removing the plants from the tower. After spraying, the plants were allowed to dry for at least two hours in a drying chimney before inoculation.
The culture of Helminthosporium sativum used for the inoculum was about three weeks old and dark black and sporulant. 5 ml of deionized water was added to each culture Petri dish and the spores were spun into water with a rubber cop. After passing into water, the water was filtered through wide cloth to separate the mycelia and agar pieces. To each 100 ml spore suspension was added one drop of surfactant ΤΪΕΕΝ80.
- 90 centimeter of spores of way; be equal to. 25 spores / ml. The inoculum was applied using a hand sprayer. Inoculated plants were placed in a greenhouse after remaining in a humidity cabinet at about 21.1 ° C (70 ° F) for twenty-four hours. The plants were allowed to stay in the greenhouse for six days before performing the assay evaluation. The disease was classified according to Clive James (Key No. 1, 1.6).
WHEAT Feather Stain (3Ntf) - Sentoria nodorum
The inoculum was prepared by placing three-week-old, swelling mycelium sections on Cza.pek-Dox V-8 plates or by placing a piece of sporulant mycelium in a test tube containing 20 ml sterile deionized water, shaking well. and placing a sufficient amount of liquid spore mixture on a fresh plate after five minutes to make a thin film on the plate. The flaps were incubated for forty-eight hours at 20 ° C in the dark until a. formation of mycelium earring. The plates were then incubated at 21 ° C under continuous fluorescent light for 15-20 days. Mycelium was pink at the end of the incubation period.
The sporulating plates were flooded with deionized water. The spores were passed to the water with a rubber policeman. Flooding and passage to water was repeated 2-3 times with each plate. The spore suspension was then filtered with wide mesh fabric. The final spore concentration was adjusted to be 150 - 300 spores / ml. Two drops of Τ7ΕΕΠ 80 were added per
<img file="PT85239B_D0073.tif" />
500 ml of spore suspension.
LEN wheat plants were inoculated by spraying the leaves with the spore suspension and T.ffiEN 30, using a hand-held sprayer after optionally lightly spraying the plants with a light mineral oil and waiting five minutes. The inoculated plants were incubated for seventy-two hours in a humid cabin at 20 ° C with an illumination period of sixteen hours of light / eight hours of darkness. The plants were then placed in a growth chamber for 7-9 days at 20Â ° C with a sixteen hour / eight hour dark period and then evaluated for percent control.
The composites were tested at different dosages depending on when the tests were performed. Test results for the best compounds that were tested are shown in Table 8 for three dosages. If the compound has been tested at the same dosage more than once, the average is given.
TABLE.A 8
FUNGICIDE ACTIVITY
Cercosporate Peanut
<td colspan="2">Like / Dosage</td><td rowspan="2">(in the 75</td><td rowspan="2">pm) 5th</td>
<td></td><td> 300</td>
<td> 4</td><td> 100</td><td> 100</td><td> 97</td>
<td> 6</td><td> 100</td><td> 100</td><td> 100</td>
<td> 7</td><td> 100</td><td> 100</td><td> 85</td>
<td> 8</td><td> 98</td><td> 100</td><td> 85</td>
<td> 11</td><td> 100</td><td> 100</td><td> 100</td>
TABLE 8 (continued)
FUNGICIDE ACTIVITY
Helminthos porium cLa Barley
Compound / Dosage (in ppm)
<td></td><td> 300</td><td> 75</td><td> 5</td>
<td> 3</td><td> 100</td><td> 99</td><td> 87</td>
<td> 10</td><td> 99</td><td> 99</td><td> 84</td>
<td> 11</td><td> 100</td><td> 99</td><td> 76</td>
<td> 16</td><td> 100</td><td> 100</td><td> 96</td>
<td> 19</td><td>Cj</td><td> -</td><td> 100</td>
<td> 25</td><td> 94</td><td> 94</td><td> 94</td>
<td> 26</td><td> 94</td><td> 97</td><td> 86</td>
Wheat Septoria nodorum
Must / Dosing (in ppm)
<td></td><td> 80</td><td> 20</td><td> 5</td>
<td> 10</td><td> 100</td><td> 100</td><td> 90</td>
<td> 49</td><td> 100</td><td> 100</td><td> 90</td>
COMPARATIVE TESTS
Compounds 2 and 10 Compared to Asarative Compounds
W — I— »IIIH« M »<nii,« i <, - ^ h »H> <mi» 'i'ii r τ -nu—- - .. ιιι ·· ιιιι -i η —.- «ι 11111 -1BIIIJ-II..MÍIII1I- iuiiiiihÍu —— Tr-Bim— · - m ·· rtl r ·: - · -Tflrr MM * C2a, C2b and C1Q
Side-by-side in vitro comparative assays of compounds 2, 10, C2a, C2b and IOC were performed for P, herpotrichoides and Septoria tritici. Assays were performed with routine PDA poison agar as follows. ?
AG AR TEST,. POISON
39 grams of potato dextrose ag-cr (PDA), purchased from Difco, is suspended in 1 liter of water. The middle was heated me one. autoclave at 1.05 kg / cm 2 (15 nsi) for fifteen minutes. After autoclaving, the medium was allowed to cool for fifteen minutes. A series of dilutions were then prepared by adding a known amount of fungicide to the molten agar. The fungicide was dissolved in methanol, acetone or DKSO before mixing with agar. Fungi were rated for growth after the following incubation periods!
Pseudpcercosporella herpotrichoides - 12 days at room temperature.
Seotoria tritici - 14 days to temperature
... .Ràr. ...............................
environment.
The results were expressed in millimeters of culture radius and the value of CEy4 was calculated. CEytj values in ppm were as follows:
<img file="PT85239B_D0074.tif" />
Pseudocercosporella
<td></td><td>G2 » (phenyl)</td><td>C2b (benzyl)</td><td>2 (phenethyl)</td>
<td></td><td> 20</td><td> 12</td><td> 0,6</td>
<td></td><td></td><td>CIO</td><td> 10</td>
<td></td><td></td><td>(benzyl)</td><td>(phenethyl)</td>
<td></td><td></td><td> 20</td><td> 0,2</td>
<td>Septoria tritici</td><td></td><td></td><td></td>
<td></td><td>C2a</td><td>C2b</td><td> 2</td>
<td></td><td> 8</td><td> 10</td><td> 0,2</td>
<td></td><td></td><td>CIO</td><td> 10</td>
<td></td><td></td><td> 4</td><td> 0,02</td>
<td>Therefore,</td><td>0 compound</td><td>according</td><td>with her</td>
invention has a ΟΕγ ^ '-'θ ·' -<sup>0 me</sup>- Twenty times smaller than the corresponding phenyl or benzyl compounds.
Compound 6 in 0-Comparative Comaration C — n——— -— | -η— * 1 *: ~ ir —imir .r ί; No comparative side-by-side in vivo testing of Compound 6 and Comparative Compound 06 was also carried out.
Barley Spot Control
High volume sprays in acetone · methanol in water were applied to a mechanical spray at.
Pennrad Barley Plants in 7.5cm Pots (3<sup>no</sup>).
- 95 44 54-7 7 < 4·<sup>:</sup> 4 · 4
The ECj CE values were calculated and pooled in Table 9. As the table shows, the compounds prepared according to the present invention have an EC CE valor value of more than twenty times lower than the corresponding benzyl compounds when The plants are treated on the day of inoculation.
SX í
Sprayed Wheat Leaf Rust Cantrol
......— ' “
47.7 74 '.' · Ν.4'7 ·> '7f4'7 · 4'47'. · '4 4 =: methanol draining,
Pennol
1-4115:- - ' .- '
-and plants with aqueous suspensions of urediospores (20,000 ml) of recondite Pttccinia and incubated for twenty <sup>s</sup>7th - '-Ri ** “* four hours at 21.1 ° C (70 ° F) in a humid environment and for an additional seven days in a greenhouse. The Î »c values were calculated and pooled in Table 9 below.
-74'4
Β / Εέ'ϊ ·? · R
common
The compounds were suspended in acetone and sprayed until the plants were mechanically sprayed on wheat plants.
Sown in 7.5 cm pots (3). Rele) Inocularag of Pulverulent Wheat Powdery Mildew
<img file="PT85239B_D0075.tif" />
Leaf spraying tests were performed
Retinfection values were calculated with Pennolum wheat plants
/' . .
ϊ ... .4. ;
!.!. ··, ··.
... :.
i ··
'.λII. 4
! ..
The.· .
li ';' Ç . ;
;...
CEyç in ppm and gathered in Table 9
- 96 Compound C6
IA γ ·. |<sub>1ψ</sub> on the day of treatment)
<img file="PT85239B_D0076.tif" />
VERULENT slightly go than
BUBBLE
I tive (inoculated from Iraq)
TABLE 9
Compound 6 (phenethyl) (benzyl)
350 can see from the data referred to in
Tabadente that the compound prepared according to then controls the barley stain better than the comparison. Although compound 6 prepared with the present invention is not one of the compounds against wheat leaf rust or against wheat mildew and the great intensity of the action of the enzyme is that against wheat fungi, the weaker compound 6 in rust control gives the comparative benzyl compound and the
4th
<img file="PT85239B_D0077.tif" />
- Compound 6 is better against the powdery mildew of wheat inoculated on the day of treatment.
Compound 10 compared to comparative compound CIO
Control of wheat powdery mildew and wheat leaf rust ~ ίρφρ · Hl g ΠΒ
The comparative test of compound [710 and comparative compound C10 was performed on two occasions, in vivo, i; Rf;
side by side using the procedure shown in Table 6. The results of both tests are as follows:
JL WPM
Compost / Dosing in ppm of ·, .ΐ !! ·;; ·.! Ί
WLR Active Ingredient
Í; '
<td></td><td> 100</td><td> 22</td><td> 6</td><td> 100</td><td> 25</td><td> 6</td>
<td> 10</td><td> 99</td><td> 95</td><td> 95</td><td> 100</td><td> 100</td><td> 99</td>
<td>CIO</td><td> 95</td><td> 95</td><td> 85</td><td> 95</td><td> 85</td><td> 85</td>
<td> 10</td><td> 100</td><td> 95</td><td> 95</td><td> 100</td><td> 100</td><td> 99</td>
<td>CIO</td><td> 100</td><td> 95</td><td> 95</td><td> 95</td><td> 85</td><td> 0</td>
and.
Kr
K. „
I *., Comparative stand against wheat leaf rust and so
Λ
Compound 10 is superior to that compared to the good compound or better than the comparative compound against wheat powdery mildew.
l ·<sup>1</sup> 4 ·., · .. liir
Based on the above comparative assays, phenethyl compounds are overall higher than corresponding benzyl and phenyl compounds. The ones with * '! H
........
<img file="PT85239B_D0078.tif" />
Stations prepared in accordance with the present invention are more than twice as good against wheat foot rot (faeudoctrcosporella). wheat leaf spot (Septoria tritici) and barley leaf (Hel 'inthosporiu' sativum) and above against wheat leaf ferruge
Bry (Bryeiphe gra «inis).
. The distinct advantage of the phenethyl triazoles prepared according to the present invention is their superior overall efficiency against a number of fungi. Preferred compounds according to the present invention have "good fungicidal activity".<sub>k</sub> barley, the 'early rice hake' is as the rust of the JitiA recondita stem) and against the powdery mildew of the leaf tricontra against the peanut stain rust and the rust of the wheat leaf wheat
According to its mechanical aspects, there is provided a process for improving the commercial value and / or profitability of salable crop crops whose orescence is affected or likely to be affected by fuhgos comprising:
i-IF .fk
In a container, a fumigation device or a mechanical spreading device, the fungicidal composition according to the present invention as described above
I<sup>1</sup>A container, fumigant or mechanical spreading device is used to apply the fungicidal composition in the form of granules, sprinkling powders, smoke, steam or liquid preparation containing a surfactant, the growing plant, 3) plant growth or a growth medium in which plants are growing or will be growing or the fungus itself; and controlling the dose of the active ingredient during the application operation so that the application dose of the active fungicidal compound is sufficient to combat the fungus but not sufficient to cause an increase in fungal activity. unacceptably adverse effect on plants d | crops that are developed or thought to develop in the treated area.
• '• I
The following words are registered trademarks that may be registered in some or all of the designated states: Hisil, Zeolex, Systhane, Liquid-M, Tween, Soltrol, Gerber, Turf-Builder.
Contents68
78 sheets
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47 members in 25 offices
Priority claims4
| Document | Office | Kind | Date |
|---|---|---|---|
| 88099086 | United States of America | A | |
| 88099086 | United States of America | A | |
| 880990 | – | – | – |
| US19860880990 | – | – | – |
Members47
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| DK336587D0 | Denmark | D0 | |
| IT8767565D0 | Italy | D0 | |
| PT85239A | Portugal | A | |
| GB8715388D0 | United Kingdom | D0 | |
| GB8723388D0 | United Kingdom | D0 | |
| IL83034A0 | Israel | A0 | |
| IL83034D0 | Israel | D0 | |
| IE871699L | Ireland | L | |
| DK336587A | Denmark | A | |
| ZA874751B | South Africa | B | |
| GB2192184A | United Kingdom | A | |
| AU7504887A | Australia | A | |
| DE3721786A1 | Germany | A1 | |
| EP0251775A2 | European Patent Office (EPO) | A2 | |
| JPS6322569A | Japan | A | |
| BR8703376A | Brazil | A | |
| HUT44415A | Hungary | A | |
| KR880001617A | Republic of Korea | A | |
| GB2197311A | United Kingdom | A | |
| FR2612741A1 | France | A1 | |
| EP0251775A3 | European Patent Office (EPO) | A3 | |
| IT1211468B | Italy | B | |
| IT8767565A0 | Italy | A0 | |
| TR23322A | Türkiye | A | |
| BE1001485A4 | Belgium | A4 | |
| PT85239BThis record | Portugal | B | |
| GB2192184B | United Kingdom | B | |
| GB2197311B | United Kingdom | B | |
| NZ220916A | New Zealand | A | |
| AU607425B2 | Australia | B2 | |
| HU203452B | Hungary | B | |
| US5087635A | United States of America | A | |
| IL83034A | Israel | A | |
| EP0251775B1 | European Patent Office (EPO) | B1 | |
| AT84789T | Austria | T | |
| ATE84789T1 | Austria | T1 | |
| DE3783669D1 | Germany | D1 | |
| GR3006830T3 | Greece | T3 | |
| DE3783669T2 | Germany | T2 | |
| CA1321588C | Canada | C | |
| AR245448A1 | Argentina | A1 | |
| EG18875A | Egypt | A | |
| IE60314B1 | Ireland | B1 | |
| JPH0655729B2 | Japan | B2 | |
| ES2053542T3 | Spain | T3 | |
| KR950003999B1 | Republic of Korea | B1 | |
| DK171399B1 | Denmark | B1 |
1 legal event, as the office reported them to INPADOC
Events
| Event | Code | |
|---|---|---|
| Annulment or lapseLapsedLAPSE DUE TO NON-PAYMENT OF FEESMM3A | MM3A |
Numbers
- Publication, DOCDB
- 85239
- Publication, EPODOC
- PT85239
- Application
- 85239
- Application, DOCDB
- 8523987
- Application, EPODOC
- PT19870085239
Titles2
- Portuguese
- PROCESSO PARA A PREPARACAO DE COMPOSICOES FUNGICIDAS CONTENDO ALFA-ARIL-ALFA-FENILETIL-1H-1,2,4-TRIAZOLO-1-PROPANONITRILOS
- English
- Process for preparing fungicidal compositions containing alpha-aryl-alpha-phenylethyl-1H-1,2,4-triazole-1-PROPANONITRILOS
Classification
- CPC, 4
- C07D231/12
- C07D249/08
- A01N43/653
- C07D233/56
- IPC, 10
- A01N43 00
- E21D9 00
- A01N43 653
- C07D249 00
- C07D249 08
- C07D401 06
- C07D403 06
- C07D405 06
- C07D409 06
- C07D521 00
