CA1133492A - 1-(2-aryl-2-r-ethyl)-1h-1,2,4-triazoles - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE

Compounds are disclosed having the formula and the physiologically acceptable acid addition salts thereof, wherein:

Ar is a member selected from the group consisting of phenyl, mono-, di- and tri-halophenyl, lower alkylphenyl, lower alkyloxy-phenyl, nitrophenyl, cyanophenyl and trifluoromethylphenyl;
and R is a member selected from the group consisting of alkyl having from 1 to 10 carbon atoms, cycloalkyl, cycloalkyl-lower alkyl, lower alkenyl, aryl-lower alkyl, aryloxy-lower alkyl and a radical of the formula -O-R1, wherein R1 is selected from the group consisting of alkyl having from 1 to 10 carbon atoms, lower alkenyl, lower alkynyl and aryl-lower alkyl, said aryl being selected from the group consisting of phenyl, naphthalenyl and substituted phenyl, wherein said substituted phenyl is phenyl having from 1 to 3 substituents independently selected from the group consisting of halo, lower alkyl, lower alkyloxy, cyano, nitro and phenyl provided that when more than 1 substituents are present only 1 thereof may be selected from the group consisting of cyano, nitro and phenyl;

these novel compounds have fungicidal and plant-growth regulating properties.

Description

34,~

BAC~GR OUND OF THE IN~ENTION:
The invention pertains to the field of 1 -(2-aryl-2-R-ethyl)-lH-1, 2, 4-triazoles which demonstrate fungicidal and plant-growth regu-lating properties. In the prior art there may be found a number of fungi_ cidal and plant-growth regulating imidazole and triazole deri~atives.
The compounds of this invention differ f_om the known triazole deriva-tivc~ by tke nature of the ~bstituted ethyl side chain present ~ the 1-position of the triazole nucleus a d from the imidazole desivative~ es-.~j3 , ;33'~

sentially by the replacement of the imidazole group with a 1H-1, 2, 4-tsiazole group.
The prior art may be represented by the following references:
U.S. Pat. No. 3,717,6~5;
U.S. Pat. No. 3,658,813;
U. S. Pat. No. 3, 9Z7, 017;
U . S. Pat. No. 3, 821, 394;
U.S. Pat. No. 3,897,43a; and U. S. Pat. No. 3, 647, 814.

DESCRIPTION OF THE PREFERRED EMBODIMENTS:

The novel 1-(2-aryl-Z-R -ethyl)-lH-l, 2, ~-triazole~ with which thi~ invention i8 concerned may structurally be represented by the formula-" N~ `
CH2-1 H-R (I) Ar wherein:
Ar is a member selected from the group consi~ting of ~henyl, mono-, di- and tri-halophenyl, lower allcylphenyl, lower al-kyloxyphenyl, nitrophenyl, cyanophenyl and trifluoromethyl-phenyl; and R is a member selected from the group consisting of aLkyl ha~nng from 1 to 10 carbon atom~, cycloalkyl, cycloallcyl-lower alkyl, lower alkenyl, aryl-lower alkyl, aryloxy-lower aLkyl and a radical of the formula -O-RI, wherein RI is selected from the group consist~g of aLkyl having from 1 to 10 carbon atoms, lower alkenyl, lower alkynyl and aryl-lower alkyl, said aryl ~13;J~

being selected from the group consisting of phenyl, naphthalenyl and substituted phenyl, wherein said substituted phenyl i9 phenyl having from 1 to 3 substituents independently selected from the group consisting of halo, lower alkyl, lower alkyloxy, cyano, nitro and phenyl, provided that when more than one sub-stituents are present only one thereof may be selected from the group consisting of cyano, nitro and phenyl.

The term "allcyl" as used in the definition of ~ and Rl is meant to in-clude straight and branch chained aliphatic hydrocarbon radicals con-taining from 1 to 10 carbons, such as, for example, methyl, ethyl, 1-methylethyl, 1, l-dimethylethyl, propyl, 1 -methylpropyl, 2-methyl-propyl, butyl, pentyl, hexyl, heptyl, octyl, decyl and the like;
"lower alkyl" as u~ed herein, refers to straight or branch chaine~
alkyl radicals containing from 1 to about 6 carbon atoms, such as, for e~cample, methyl, ethyl, l-methylethyl, propyl, l-methylpropyl, 2-methylpropyl, butyl, pentyl, hexyl and the like; "lower alkenyl" refers to straight and branch chained unsaturated alkenyl radical~ having from 3 to 6 carbon atoms, such as, for example, 2-propenyl, 1-methyl-2-- propenyl, 2-butenyl, 3-butenyl, 2-hexenyl and the lilce; the term "cycloalkyl" refers to cyclic hydrocarbon radicals having rom 3 to 6 carbon atom~, such as cyclopropyl, cyclobutyl, cyclopentyl a~d cyclohexyl; and the term "halo" is generic to halogens of atomic weight less than 127, i. e., chloro, bromo, fluoro and iodo.

The physiologically acceptable acid addition sales of the fore-goi g compounds (I) are also embraced within the scope of this inven-tion.

3~

One preferred group of co~slpounds within the scope of formula (I) may be repre~ented by the for~nula:

N
N` NJ~

2 (~;
Ar' wherein A~' is ~elected from the group consisting of phenyl, mono-and di-halophenyl, and methylphenyl; and R' is selected from the group consisting of alkyl having f:rom 1 to 10 carbon atoms, cycloalkyl, lower alkenyl, aryl-methyl and arylethyl, wherein ~aid aryl is preferably phenyl, halophenyl, methylphenyl or methoxyphenyl.

Especially preferred within the scope of formula (I') are compounds wherein Ar' i~ phenyl, chlorophenyl, fluorophenyl, bromophenyl, di-chlorophenyl, dibromophenyl or methylphenyl, the most preferred being diclLloro- and dibromophenyl; and, wherein R ' is alkyl having from 1 to 8 carbon atoms, cycloa~kyl, or 2-propenyl, the most preferred being alkyl having from 1 to 6 carbon atoms and 2-propenyl.

Typical exampleb of preferred compounds within the scope of formula (I') are the follow~g: .
2-(2, 4-dichlorophenyl)propy~7-IH-1, Z, 4-triazole;

I ~r-(2, 4-dichlorophenyl)buty~-lH-1, Z, 4-triazole;

1-/~-(Z, 4-dichlorophenyl)penty~7-lH-1, 2, 4-triazole;

1-~-(2, 4-dichlorophenyl)-3-methylbuty~7-lH-1, 2, 4-triazole;

1 1;3t~ 'r3~

1 -~-(2, 4-dichlorophenyl)-4-penteny~7-lH-1, 2, 4-triazole;

I - LZ-(2, 4-dichiorophenyl)hexy~ 1H-1, 2, 4-triazole;

l -~-(2, 4-dichlorophenyl)-4-methylpenty~7-lH-1, 2, 4-triazole;

1-~-(2, 4-dichlorophenyl)-3-methylpenty~7-lH-1, 2, 4-triazolei - 5 1-~-(2, 4-dichlorophenyl)hepty~7-lH-1, 2, 4-trlazolei 1 -~-cyclopentyl-2-(2, 4-dichlorophenyl)ethyy-lH-1, 2, 4-triazole;

1 -~-cyclohexyl-2-(2, 4-dichlorophenyl)ethy~7-lH-1, 2, 4-triazole;

1-~-(4-chlorophenyl)-2-(2, 4-dichlorophenyl)propy~-lH-1, 2, 4-tsiazole;

1-~-(2, 4-dibromophenyl)hexy~7-lH-1, 2, 4-triazole;
l -~-(2, 4-dibromophenyl)-4-methylpenty~7-lH-1, 2, 4-tr~azolei l -/~-(2, 4-dibromophenyl)-3-methylbuty~-lH-1, 2, 4-triazole;

1-~-(2~ 4-dibromophenyl)-3-methylpenty~7-lH-1, 2, 4-triazole;

1- ~-(4-nuorophenyl)-4-(4-methylphenyl)buty~7-lH-1, 2, 4-triazole; and i 5 l -~-(4-chlorophenyl)-2 -(4-fluorophenyl)buty~-l H - 1, 2 , 4-triazole .

Another preferred group of compounds of formula (I) are repre~ented by the formula: ~

N~N (I") CH2 -CH -O-R "
Ar' wherein Ar' is as def~ed above and R" i8 selected from the group con~isting of alkyl having from 1 to 10 carbon atom~, lower alkenyl and lower alkynyl.
E6pecially preferred compoundq within the scope of formula (I") are those wherein Ar' is phenyl, chlorophenyl, fluorophe~yl, bromo-phenyl, dichlorophenyl, dibromophenyl or rrethylphenyl; the most preferred being dichloro- and dibromophenyl; and, wherein R" is alkyl having from 1 to 8 carbon atom~, 2-propenyl or 2-propynyl, the most p-eferred alkyl~ having from I to 6 carbon atoms.

Typical preferred compounds of formula (I") are, for example, the following:

1 -~-(2, 4-dichlorophenyl)-2-ethoxyethyl7-lH-1, 2, 4-triazole;

1-~-(2, 4-dichlorophenyl)-2-propoxyethy37-lH-1, 2, 4-triazole;

1-~-(2, 4-dichlorophenyl)-2-(2-propenyloxy)ethy~7-1H-I, 2, 4-triazole;

1-~-butoxy-Z-(2, 4-dichlorophenyl)ethy~-lH-1, 2, 4-triazole;

1-~-(2,4-dichlorophenyl)-2-(pentyloxy)ethy~-lH-1,2,4-tria~ole;

1-~-(2 , 4-dic}~l orophenylj -2 -(hexyloxy)ethy~7- lH - 1, 2 , 4-triazole;

1 -C-(2, 4-dichlorophenyl)-2-(heptyloxy)ethy~7-lH-1, 2, 4-triazole; and 1-~-(2, 4-dichlorophenyl)-2-(2-methylpropoxy)ethy~7-lH-1, 2, 4-triazole.

-The compounds of for~nula ( I ) which may be represented by the formula:

.' ' , ~ z.

Ar ( I-a ) .
wherein Ar is a previously defined and R is selected ~rom the group consisting of alkyl, cycloalkyl, cycloalkyl-lower alkyl, lower alkenyl,-aryl-lower alkyl and aryloxy-lower alkyl, may conveniently be pre-pared by N-alkylating lH-l, 2, 4-triazole ( II ) with an appropriate reac-tive ester of formula (III ) wherein Ar and R2 are as previously defined and X i8 a reactive ester function such as, for example, halo, methyl-sulfonyloxy, ~4-methylphenyl)sulfonyloxy and the like.

lû In carrying out the reaction of ( II ) and (III ) it is appropriate to first convest ( II ) into an alkali metal salt, preferably the sodium salt, by the reaction of ( II ) with an appropriate strong metal base, such as, for example, sodium hydride, sodium methanolate, sodium amide and the like and thereafter stirring and heating said metal salt with (III) in an appropriate polar organic solvent. Suitable solvents for this purpose include amides such as, for example, N,N-dimethylform-amide and N,N-dimethylacetamide, and nitriles such as, for example acetonitrile, benzonitrile and the like.

Alternatively ( II ) and (III ) may be reacted directly with each other w~thout previous salt formation, in which case the reaction is preferably carried out in an appropriate polar organic solvent as defined hereabove, in the presence of an appropriate base to pick up the acid which is liberated during the course of the reaction. Suitable bases which may advantageously be employed include inorganic bas.es such as, for example, sodium and potassium carbonate and hydrogen carbonate and the like, and organic bases such as, for example, N,N-diethylethanamine, pyridine and the like. Somewhat elevated tempera-tures are appropriate to enhance the rate of the reaction and most preferably the reaction is carried out at the reflux temperature of the reaction mixture.

-- The foregoing reactions may be illustrated as follows:

~,¦1 NaOCH3 r( II ) 1 + X-CH2-CH-R2 ~N > Lsodium salt~ lr (II) (III) j_N
>N~JJ
~;H2 - CH -R 2 Ar ( I-a ) ( II ) ~ ( III ) base ( I-a ) solvent The compounds of formula ( I ) which are represented by the formula:

N
~,!J

f r ( I-b )

3~

wheréin Ar and R are as pre~iously deined may be prepared by 0-alkylating a hydroxy compouncl of the formula ( IV ) with an appropriate reactive ester of formula XR ~ wherein R and X are as previously defined following standard procedures of 0-alkylation. In a preferred method of carrying out said 0-a~ylation reaction the hydroxycompound ( IV ) is first converted into an alkali metal salt thereof by treating ~ IV ) with an appropriate metallating agent such as, for example, ~odium hydride, sodium meth~nolate, sodium amide and the like whereafter the resulting metal salt is reacted with XR . Said reaction i8 carried out in an appropriate reaction-inert organic solvent such as, for example, an aromatic hydrocarbon, e. g. benzene, methylbenzene and the like;
a ketone, e. g., 2-propanone, 4-methyl-2-pentanone and the like; an ether, e.g., 1~ l'-oxybisethane, 2,2'-oxybispropane and the like; an amide,- e.g., N,N-dirnethylformamide, N,N-dimethylacetamide; or another common solvent such as, for example, dimethylsulfoxide, nitro-benzene and the like; or in a mixture of such solvents.

N~NJ ~lalt formation ~ + XR ~ (I-b ) CH2-CHOH etal salt r '` (IV) .
It is evident that the compounds of formula (I ) obtained following the procedure6 described hesebefore are isolated from the reaction mixture and, if nece6sary, further pur;fied by the app'ication of methodologies known in the art.

The compounds of formula ( I ), obtained in base form in the foregoing procedures, may be con~rerted to their physiologically accep-table acid addition salts by the reaction with an appropriate acid, as, for example, an inorganic acid such as hydrohalic acid, i. e., hydro-chloric, hydrobromic or hydroiodic acid; sulfuric, nitric or thiocyanic acid; a phosphoric acid; an organic acid such as acetic, propanoic, _9_ hydroxyacetic, 2-hydroxypropanoic, 2-oxopropanoic, ethanedioic, propanedioic, butanedioic, (Z)-2-butenedioic, (E)-2-butenedioic, 2-hydroxybutanedioic, 2,3-dihydro~ybutanedioic, 2-hydroxy-1,2,3_ propanetricarboxylic, benzoic, 3-phenyl-2-propenoic, a-hydroxy--benzeneacetic, methanesulfonic, ethanesulfonic, hydroxyethanesulfonic,

4-methylbenzenesulfonic, 2-hydroxybenzoic, 4-amino-2-hydroxy-benzoic, 2-phenoxybenzoic or 2-acetyloxybenzoic acid. The salts are in turn converted to the corresponding free bases in the usual manner, e. g., by reaction with al~cali such as sodium or potassium hydroxlde.

A number of the reactive ester intermediates of forrnula(III) are known compounds and they may all be prepared according to art-known procedures as described in the literature for the preparation of those known compounds. Such compounds and methods of preparing the same are described, for example, in U. S. Pat. No. 3, 927, 017.

In general said in~ermediates of forml~la ( III ) are prepared by converting the corresponding alcohol ( V ) iuto the desired reacti~re ester according to methodologies generally known in the art. ~or example, methanesulfonates and 4-methylbenzenesulfonates are easily obtained by treating the alcohol with methanesulfonyl chloride or 4-methylbenzenesulfo~yl chloride respectively, in the presence of an appropriate acid acceptor, such as, for example, pyridine. Halides - . may be obtained by treating the alcohol with an appropriate halogenating agent, such as, for example, phosphor pentachloride, phosphorous tribromide, etc HO-CH -CH-R2 reactive ester (III) 2 l formation r ( V ) 113;~

The intermediate alcohols of formula (V ), a number of which are known compounds, may be prepared according to lcnown procedures, such as, for example, the following:

An appropriately substituted arylacetonitrile of formula (VI ) is allcylated with an appropriate reactive ester R2X, (~II ). Said aL'cylation reaction is preferably carried out by contacting first the aryl-acetonitrile with an appropriate strong base, such as, for example, sodium hydride, and thereafter adding the reactive ester to the reaction mixture. Suitable ~olvents for this reaction include amides such as N, N-dimethylformamide, N,N-dimethylacetamide and hexamethylphosphoric triamide, other common polar solvents such as dimethylsulfoxide, or mixtures of such solvents with, for example, an aromatic hydrocar~on, such as, benzene.

The substituted arylacetonitrile (VIII ) obtained in the fore-going step is then converted into an aLkyl ester ( IX ) of the corresponding carboxylic acid. This nitrile-to-ester conversion may be achieved in one step, fos example, by heating the nitrile in an appropriate alcohol, or a mixtuse of an alcohol with an appropriate reaction-inert organic sol-vent, such as, 2,2'-oxybispropane, in the presence of a stsong non-oxidizing mineral acid such as, for example, hydsochloric acid. Alter -natively the nitrile may be first hydrolyzed to the corresponding aryl-acetic acid in the usual manner, e. g., with sodium hydroxide in 1, 2-ethanediol, and said acid may thereafter be converted into the desired ester thereof by classical means.

- 25 The esters ( IX ) may also be obtained by alkylating an appro-priate aLt~yl arylacetate ( X ) with R X according to known procedures .

The alcohols ( V ) are then obtained after reduction of ( IX ) with an appropriate reducing agent such as, for example, lithium-aluminiu;n hydride, lithium borohydride, or sodium borohydride in the presence of a lithium salt, preferably a halide such as, lithiurn iodide or lithium chloride.

1~3;~ 3~

. .

The foregoing reactions are illustrated in the following schematic representation:
.

r C 2 R X R 2 ( VI ) ( VII ) ( VIII ) +
H alkanol O O
Ar-CH2_1C!-O-alkyl ~ R X Ar-CH-~-O-alkyl (X) (VII) (IX) (IX ) 4 > (V ) The starting materials of formula (VI ) and (VII ) herein are generally known and may be prepared following art-h~own procedures.
For example, starting materials of formula (VII) wherein R2 stands for aryloxy-lower alkyl and X stands for halo, are easily prepared by O-alkyl~ting an appropriate hydroxyarene with an appropriate dihalo-lower alkane using, for example~ aqueous alkali as a reaction medium.

Intermediates of formula ( IV ) and a method of preparing them are described in Ger. O. L. S. No. 24. 31. 407. According to said refer-ence the intermediates ( IV ) may be derived from the correspon~;ng ketones (XI ) by reducing the latter with aD appropriate reducing agent such as, for example, aluminium 2-propanolate, complex hydrides -12_ such as, sodium borohydride or by catalytic hydrogenation using an appropriate catalyst such aa, for example, Raney-nic~el.

An other and novel method of preparing the intermediates of formula ( IV ) is by the reaction of 1H-1, 2, 4-triazole ( II ) with an appropriate reactive ester of forrnula ( XII ) wherein X is a reactive ester group as previously defined, following similar procedures as described hereinabove for the preparation of the compounds ( I ) ~tarting from ( II ) and ( III ).

- The foregoing reactions are illustrated in the following schematic representation:
.

~NI~lreduction (IV ) CH2 ~C O
Ar (XI) ( II ) + X-CH2-~HOH ~ IV ) r - (XII) The ultimate starting materials in each of the foregoing procedures are generally known and they may all be prepared following art-lenow~ prodecures.

Due to the presence of an asymmetric carbon in the subject compounds ( I ), it is evident that their existence in the form of stereo-chemical optical isomers (enantiomers) is possible. If desired, she resoiution and isolation or the production of a particular form can be accomplished by application of the general principles known in the art.
Said enantiomers are naturally intended to be included within the scope of this invention.

3 ~ ~ Z

The compounds of formula ( I ) and the acid addition salts thereof are useful agents in combatting fungi. They are especially useful as potent agricultural fungicides, being active against a wide variety of fungi such as, for example, those responsible for the occurrence of powdery mildew on different plant species, e. g., Erysiphe graminis, Erysiphe polygoni, Erysiphe cichoracearum, Erysiphe polyphaga, Podosphaera leucotrichia, Sphaerotheca pannosa, Sphaero-theca mors-uvae and Uncinulla necator; and against other phytopatho-genic fungi such as, for example, Septoria apii and Uromyces phaseoli.

The useful antifungal properties of the compounds of this i~lvention are more clearly illu~trated by the results obtained in the following experiments. The compounds for which experimental data are presented hereafter are not given for the purpose of limiting the invention thereto but only to exemplify the useful antifungal properties of all the compou~ds within the scope of formula (I).

~3;3~

A Prophylactic acti~ity against Erysiphe cichoracearum on gherkins upon foliar treatme~t.

Young gherkin plants, about lO days old, were sp~ayed with an aqueous solution containing 100, lO or l ppm. (parts per million) of the compound to be tested, while controls were kept ~ ntreated. After drying of the plants, artificial infection with spores of Erysiphe cicho-racearum was carried out by slightly rubbing the plants with a heavily infected leaf. At the 15th day after artificial infection the degree of fungal attack was evaluated by estimating the percent of leaf su_~ace attacked by the fungus. Three plants were used per object and mean values were calculated for these 3 plants. The results are presented inTables I asld II according to the following score system:

acore % of leaf surface attacked O O ' - 1 ~.lO
2 ll to50 3 ~50 - TABLE I: Prophylactic acti~ity a~ainst Erysiphe cichoracearum on gherkins (foliar treatment).

Nl ~rNJJ
CH - CH -R
2~1 Bas eScor e s =
Compound R . Salt100 ppm 10 ppm. 1 ppm 1 CH3 bas e O O O
2 C2H5 bas e O O O
3 nC3H7 bas e O O O
4 i C3H 7 HN03 O O O
nC4H9 HN03 O O ' O
6 CH2 -CH(CH3)2 HN03 O O O
7 CH(CH3)-CH2 -CH3 HN03 O O O
8 nC8H 17 HN03 O O 2 9 CH2 -CH =CH2 HN03 O O O
{~ HN03 O O
11 -0 base O . 1 2 12 ~CH2)2{1 base O 1 2 13 CH20 HoN503H2C l 3 3 14 (CH2)2 ~0 base O O 2 l 5 CH2 -(4-Cl-C6H4) HN03 O O 3 l 6 CH2-(2-Br-C6H4) HN03 O O O
l 7 CH2-(4-C6Hs-c6 4) HCl O O 2 18 (CH2)2-0-(4-Br -C6H4) HN03 O O 3 .
_ _ _ _ _ _ _ _ _ _ ( CHz)3- o - ( 3~ 5 -C l2 c 6 3 ) HN0 3 _ _ _ _ _ _ _ . _ _ _ _ _ _ _ - - -3 - ~ .

. . .

_16-4tr~ ' TA3LE I (cont'd) _ _ ___ __ __ _ _____ _ __ _ _ ___ __ __ __ __ _ _ _ Bas ë 1 Scores Compound R . or no. Salt 100 ppm. 10 ppm. ppm . 20 (CH2)3-0 -(3 -CH3-4-Cl-C6H3) HN03 1 3 3 21 (CH2)3 ~0~~ -CH3-4-Cl-C6H3) HN03 1 0 2 22 (CHz)3-O-~ -Br-4-CH3 -C6H3) HN03 0 0 23 (CH2)3-0-(2.4-C12-6-CH3- HN03 2 2 3 C6 2) 24 (CH2)3-0_(2, a,6 Br3 HN03 0 0 C6H2 ) (CH2)3 -0-(2 -Cl-4-C6H5 - HN03 0 1 2 C6H3) 26 (CH2)3 -0-(2 -naph~halenyl) HN03 O O 2 29 0-nG3H7 HN03 0 0 0 0 -nC4H9 HN03 0 0 0 31 0-nC5Hl l HN03 0 0 33 nC7H15 HN03 0 0 34 0-CHz-CH=CH2 HN03 0 0 0 3i ~ C~32 ~ C--CH ba ~I c O O 2 .

TABLE II: Prophylactic activity against Erysiphe cichoracearum on gherkins (foliar treatrne~t).

N
` IN~

Ar Compound Ar R Base Scoses no. Salt 100 ppm 10 ppm. 1 36 ~, 4-Br2-C6H3 nC4H9 HNO3 0 0 0 37 2 -Cl-C6H4(CH2)2 -(4-Br-C6H4) HCl 0 1 2 33 4-~;l^C6H4CH2)2-(4-Cl-C6 4) HCl O 1 2 ~- 39 4-Br-C6H4CH2)2-(4-Cl C6; 4) base 0 2 3 4-Br -C6H4CH2)2 -(2 -OCH3 ~ HCl 0 1 2 41 4-Br-C6H4(CH2)2 -(4-Br-C6H4) HCl 0 3 3 42 4 F`C HCH2)2-(4-Cl-c6H4) HCl _ 0 43 4-F-C6H4 C~ 6H4) HCl 0 0 .44 4-CH3-C6H4CH2)2 ~(4-Cl-C6H4) HCl 0 2 3 B; Prophylactic action against Erysiphe graminis on barley upon foliar tr eatment .

Young barley plants, about 8 cm. high, were sprayed with an aqueous solution containing 100, 10 or 1 ppm. o the compound under investigation while controls were kept untreated. After drying of the plants they were artificially infected by dusting them with conidia of Erysiphe graminis. Fungal attack was evaluated 10 days thereafter in the same manner as described in experiment A The results of this experiment are represented in Table III wherein the compound numbers and the score system are the same as in Tables I and II.

TABLE III: Prophylactic action against Erysiphe graminis on barley upon foliar treatment.

_ Scores Compound no. 100 ppm 10 ppm 1 ppm.

___________-______________ ___________ ____________ _________ 113;~

TABLE II (cont'd) ._____________________________.~___________________________________ Compound no. Scores 100 ppm. I 10 ppm. 1 ppm.

_20 -~13;3~9Z

.

C. Systemic activity against Erysiphe cichoracearum on gherkins.

Young gherkin plants, about 10 days oid, where treated by watering of the soil with an aqueous solution of the test compound.
Per plant 100 ml. were given and the total amount of test compound was 10 or 1 mg. per plant. Controls received the same amount of the solution without active ingredient. 4 Days thereafter the plants were artificially infected with Erysiphe cichoracearum by slightly rubbing the plants with a heavily infected leaf. Evaluation of fungal attack was done 15 days thereafter in the same manner as described in test A.
The results are given in table IV wherein the compound numbers and the score system are the same as in tables I and II.

TABLE IV: Systemic activity against Erysiphe cichoracearum on gherkins.
-_ Score8 Compound no. 10 mg. /plant 1 mg. /plant ___________ __________________ ______________________ . .

3~
~.

.
TABLE IV (cont'd) ____________________. ____________________________________ Scores Compound no.
10 mg ~plant I mg /plant _ ~ Z

I). Prophylactic activity against Uromyces phaseoli on bean~ upo foliar treatment.

Young bean plants, about 15 cm. high, were sprayed with an aqueous solution containing 250, 100 or 10 ppm. of the test compound while controls were kept untreated. After d~ying, the plants were artificially infected by spraying them with a suspension of spores of - Uromyces phaseoli. Subsequently the plants were incubated for 24 hours at 18C and at 95-100% relative humidity. Fungal attaclc was eval~ated 10 days a$er the artiicial infection in the same manrler as in test A.
The results are given in table V wherein the same compound numbers and the same score system as in tables I and II are used.

113~

TABLE V: Prophylactic activity against Uromyces phaseoli on beans upon foliar treatment.

Compound no. Scores 250 ppm. 100 ppm. 10 ppm.

: ~ ~

_23 -~13;~

- Apart from their antifu3~gal effect, the compounds of - formula (I) possess valuable plant growth regulating properties.
Depending on different factors such as the species of the plants under investigation and the dose of active ingredient administered, the observed effect may be growth stimulation or growth inhibition.
As such the compounds of this invention are useful as plant growth regulators and this useful property is naturally intended to be also within the scope of this invention.

In view of the aforementioned antifungal and growth-. egulating activities this invention provides valuable compositions comprising the su~ject triazoles ( I ) or the acid addition salts thereof as the active ingredient in a solvent or a solid, semi-solid or li~uid diluent or ca-_ier, and, in addition, it provides an effective method of combatting fungal growth by use of an effective antifungal amount of such triazoles ( I ) or salts thereof. The ~ubject compounds can be used in suitable solvents or diluents, in the form of esnulsions, suspensions, dispersions or oint-ments, on suitable solid or sem -solid carrier substances, iQ ordinary or synthetic soaps, detergents or dispersion media, if desired, together with other compound~ havi~lg arachnicidal, insecticida~, ovicidal, fungi-cidal and/or bactericidal effects, or together with inactive additives.

Solid carrier substances which are suitable for the prepara-tion of compositions in powder form include various inert, porous and pulverous distributing agents of inorganic or organic nature, SUCQ as, for example, tricalcium phosphate, calcium earbonate in the form of prepared chalk or ground limestone, kaolin, bole, bentonite, talcum, kieselguhr and boric acid; powdered cork, sawdust, and other fine pulverous materials of vegetable origin are also suitable carrier substances .

--24_ .

~13;~

The active ingredient is mixed with these carrier substances, for example, by being ground therewith; alternatively, the inert carrier substance is impregnated with a solution of the active component in a readily volatile solvent and the solvent is thereafter eliminated by hea-ting or by filtering with suction at reduced pressure. By adding wetting and/or dispersing agents, such pulverous preparations can also be made readily wettable with water, so that suspensions are obtained.

Inert solvents uced for the production of liquid preparations should preferably not be readily in1ammable and should be as far as possible odorless and as far as possible non-toxic to warm-blooded animals o, plznts in the relevant surroundings. Solvents suitable for this purpose are high-boiling oils, for example, of vegetable orig.n, and lower-boiling solvents with a flash point of at least 30C, such as, for example, polyethylene glycol, isopropanol, dimethylsulfoxide, hydro-genated naphthalenes and alkylated naphthalenes. It is, of course, also - possible to use mixtures of solvents. Solutions can be prepared in theusual way, if necessary, with assistance of solution promotors. Other liquid forms which can be used consist of emulsions or suspensions of the active compound in water or suitable inert solvents, or also con-centrates for preparing such emulsions, which can be directly adjusted to the required concentration. For this purpose, the active ingredient is, for example, mixed with a dispersing or emulsify~ g agent. The active component can also be dissolved or dispersed in a suitable inert qolvent and mixed simultaneously or subsequently with a dispersing or emulsi-fyina agent.

It is also possible to use semi-solid carrier substances of a cream ointment, paste or waxlike nature, into which the active com-ponent can be incorporated, if necessary, with the aid of solution promo-tors and/or emulsifiers. Vaseline and other cream bases are examples of semi-solid carrier substances.

_25 -.

Furthermore, it is possible for the active component to be used in the form of aerosols. For this purpose, the active component is dissolved or dispersed, if necessary, with the aid of suitable inert solvents as carrier liquids, such as dif~uorodichloromethane~ which at atmospheric pressure boils at a temperature lower than room tem-perature, or in other volatile solvents. .In this way, solutions under pres-sure are obtained which, when sprayed, yield aerosols which are par-ticularly suitable for contrqlling or combatting fungi, e. g., in closed chambers and storage rooms, and for application to vegetation for eradicating or for preventing infections by fungi.

The subject compounds and compositions thereof can be applied by conventional methods. For example, a fungal growth or a material to be treated or to be protected against attack by fungus can be treated with the subject compounds and the compositions thereof by dusting, sprinlcling, spraying, brushing, dipping, smearing, impregnating or other suitable means.

W}~en the subiect compounds are employed in combination with suitable carriers, e. g., in solution, suspension, dust, powder, ointment, - emulsion, and the l~ce forms, a high activity over a very high range of dilution is observed. For example, concentrations of the active ingre-dient ranging from 0.1 - 10 percent by weight, based on the weight of composition employed, have been found effective in combatting fungi.
Of coursej higher concentrations may also be employed as warranted by the particular situation.

Z5 The following examples are intended to illustrate, but not to limit, the scope of the present invention. Unless otherwise stated, all parts are by weight.

34~

- XAMPLE I

To a stirred and refluxing mixture of I22 parts of 4-chloro-3_methylphenol, 214. 1 parts of 1, 3-dibromopropane and 850 parts of water is added dropwise, during a one hour-period, a solution of 34 parts of sodium hydroxide in 213 parts of water. Upon cornpletion, stirring at reflux is continued overnight. The reaction ~ixture is cooled to room temperature and the pToduct is extracted with 765 parts of benzene. The extract is washed with a sodium hyd~oxide solution 10%, dried, filtered and evaporated. The residue is distilled twice, yiel~ing 114 parts of 4-(3-bromopropoxy)-1-chloro-2-methylbenzene; bp. 119~C
at 0 . 6 mm. pres suse.

EXAMPLE II

Following the procedure of Example I and using an equivalent amount of an appropriate substituted phenol in place of the 4-chloro-3-methylphenol used therein the foLlowing intermediate compounds are prepared:

1-(3-bromopropoxy)-4-c}lloro-2-methylbenzene;bp. 1 15-1 16C at 0. 6 mm pressure;

2-(3-bromopropoxy)-1, 5 -dichloro-3-methylbenzene;bp. 118 C at 0. 6 mm. pre~sure;

4-(3-bromopropoxy)-3-chloro-[, 1 '-biphenxi7;

2-bromo-1-(3-bromopropoxy)-4-methylbenzene;bp. 123-126C at 0.8 mm pressure; and 1, 3, 5-tribromo-2 -(3-bromopropoxy)benzene. bp. 160 -177 C .
.

_27 -4q~

EXAMPLE III

To a stirred and cooled (water-bath) suspension of 7 parts of a sodium hydride dispersion 78 % in 75 parts of dimethylsulfoxide is added dropwise, during a 30 minutes-period, a solution of 37 parts of 2,4-dichloroben7eneacet~nitrile in 100 parts of dimethylsulfoxide.
The whole is stirred for 30 minutes while cooling in a water-bath.
Then there is added dropwise, during a 30 ~ninutes-period, a solution of 56 parts of 1-bromo-4-(2-bromoethoxy)benzene in 1~5 parts of di-methylsulfoxide and stirring is continued for another 30 minutes. The reaction mixture is poured onto water and the product is extracted twice with 2, 2'-oxybispropane. The combined extracts are washed twice with water, dried, filtered and e~aporated. The residue is triturated in petroleumether. The product is filtered off and crystallized f om ethanol, yielding 38 parts of -,~-(4-bromophenoxy)ethy~7-2,4-di-chlorobenzeneacetonitrile; mp. 73. 9G.
.;

EXAMPLE IV

A mixture of 18.5 parts of 2,4-dichlorobenzeneacetonitrile and 180 parts of N,N-dimethylformamide is stirred and cooled i~ an ice-bath while nitrogen gas is introduced. 3. 2 Parts of a sodium hydro-xide solution 78 % are added portionwise and the whole is stirred for one hour. Then there are added dropwi~e, during a one hour-period, 17. 8 parts of (bromomethyl)cyclohexane while still cooling and while nitrogen gas is still introduced. Upon completion, stirring is continued for 2 }~ours at room temperature. The reaction mixture is poured onto water. The precipitated product is iltered off and triturated in a mix-ture of methanol aud water. The product is filtered off and dried, yiel-ding 25.5 parts of 2,4-dichloro-a-(cyclohexylmethyl)benzeneacetonitrile;
mp. 58. 8C.

-2~ _ ,3~
.

EXAMPLE V

By repeating the procedure of Example IV and using equi-valent arnounts of the appropriate starting materials, there are prepared:

a-(3-butenyl)-2,4-dichlorobenzeneacetonitrile; bp. 104-108C at 0.1 mm. pressure; and 2, 4-dichloro-a-(2 -cyclopentylethyl)benzeneacetonitrile; bp. 130-135 C
at 0 . 05 mm. pres sure.

EXAMPLE VI

To a stirred and cooled (ice-bath) mixture of 27. 5 parts of 2,4-dibromobenzeneacetonitri~e, 135 parts of N,N-dimethylformamide and 67. 5 parts of benzene are added portionwise 3. 2 parts of sodiu:n hydride dispersion 78% while rlitrogen gas i5 introduced. After stirring or one ~iour, 14 parts of l-bromobutane are added dropwise. Upon completion, stirr~ng is continued for 2 hours at rocm temperature. The reaction mixture is poured onto water and the product is extracted twice with 2, 2'-oxybispropane. The combined extracts aTe washed twice with water, dried, filtered and evaporated. The residue is distilled, yielding 22 parts of 2, 4-dibromo-a-butylbenzeneacetonitTile; bp. 124C at 0.05 mm. pressure.

EXAMPLE VII

By repeating the procedure of Example VI and using an equivalent zmount of respectively an appropriate bromide and an appropriate arylacetonitrile in place of the 1 -bromobutane and the 2, 4-dibromobenzeneacetonitrile used therein the followis~g compounds are prepared:

3~

Z, 4-dichloro-a-~-(4-chlorc>-3-methylphenoxy)propy~benzeneaceto-nitrile; bp. 216-Z19~C at 0. 05 mm. pressure;

2, 4-dichloro-a-~-(3, 5-dichlorophenoxy)propy~7benzeneacetonitrile;
bp. 210-215C at 0. 05 mm. pressure;

2, 4-dichloro--~-(2-naphthalenyloxy)propy~benzeneacetonitrile;
mp. 100C;

a-~-(2-bromophenoxy)propy~7-2,4-dichlorobenzeneacetonitrile; mp.
61. 2C;

2, 4-dichloro-a-r-(4-chloro-2-methylphenoxy)propy~7benzeneaceso-nitrile; mp. 73C;

2, 4-dichloro-a-~-(2, 4-dichloro-6-methylphenoxy)propy~7benzene-acetonitrile; bp. 212-Z16C at 0. 05 mm. pressure;

2,4-dichloro--~-(3-chloro-~ bipheny~7-4-yloxy)propy~7-benzeneacetonitrile; mp. 70 . 3 C;

a-~-(2-bromo-4-methylphenoxy)propy~7-Z, 4-dic lorobenzeneaceto-nitrile; bp. 215-219C at 0.05 mm. pressure; and ~ .
2, 4-dichloro-a-,~-(2, 4, 6-tribromophenoxy)propy~7benzeneaceto-nitrile; mp. 85.2C.

EXAMPLE VIII

To a stirred mixture of 18.5 parts of 2,4-dichlorobenzene-acetonitrile, 90 parts of N,N-dimethylformamide and 67.5 parts of benzene are added portiorwise 3. 2 parts of a sodium hydride dispersion 78 % while nitrogen gas is introduced. After stirring for 1 hour at room temperature, 14. 5 parts of (2-chloroethyl)cyclohæxane are adde~.
_ ~ b~

~3;~
-The whole i9 stirred first for 5 hours at 40-50C and further overnight at room temperature. The reaction mixture is poured onto water and the product is extracted twice with 2, 2'-oxybispropane. The combined ex-tracts are washed twice with water, dried, filtered and evaporated.
The residue is distilled, yielding 16 parts (54~0) of 2,2'-dichloro-a-(2-cyclohexylethyl)benzeneacetonitrile; bp. 145-148C at 0.05 mm.
pres sur e .

EX~MPLE IX

Following the procedure of Example VIII and using equivalent amounts of the appropriate starting materials, there are prepared:

a-(2, 4-dichlorophenyl)-C, 1 ' -bipheny~7-4-propanenitrile; bp. 215-230 C at 0 . 05 mrn. pres sure;

- 2, 4-dichloro--(2, 4-dichlorophenyl)benzenebutanenitrile as an oily- residue;
, 4-chloro--(4-chlorophenyl)benzenebutanenitrile as an oily residue;

4-chloro--(4-methylphenyl)benzenebutanenitrile; bp. 175-178C at - 0.1 mm. pressure;

ot_(4-bromophenyl)-2-methoxybenzenebutanenitrile as an oily res~due;

a-(4-bromophenyl)-4-chlorobenzenebutanenitrile as an oily residue;

4-chloro--(4-fluorophenyl)benzenebutanenitrile; bp. 165-168C at 0.1 mm. pressure;

-(4-1uorophenyl)- -methylbenzenebutanenitrile; bp. 160-165C at - O. 3 mm. pressure;

~3;~

4-bromo--(2-chlorophenyl)benzenebutanenitrile; bp. 176-180C at 0. 1 mm. pressure; and 4-bromo--(4-bromophenyl)benzenebutanenitrile as an oily residue.

EXAMPLE X

120 Parts of methanol are saturated with gaseous hydrogen chloride while cooling in an ice-bath. Then there are added 22 parts of 2, 4-dibromo-a-butylbenzeneacetonitr;le and the whole is stirred and re1uxed overnight. The reaction mixture is cooled and poured onto water. The product is extracted with 2, 2'-oxybispropane. The extract is washed with water, dried, filtered and evaporated. The residue is distilled, yielding 16.S parts (68%) of methyl 2,4-dibromo--butyl-benzeneacetate; bp. 125C at 0.1 mm. pressure.
, EXAMPLE XI

; Follo~ing the procedure of Example X, the following esters are prepared start~ng from the appropriate nitriles:

methyl cc-t3-butenyl)-2,4-dichlorobenzeneacetate as a residue;

methyl 2, 4-dichloro--(cyclohexylmethyl)benzeneacetate as a residue;

methyl 2,4-dichloro--(2-cyclopentylethyl)benzeneacetate as a residue;

methyl 2, 4-dichloro--(2-cyclohexylethyl)benzeneacetate as a residue;

methyl -(2, 4-dichlorophenyl)-~, 1 '-bipheny~7-4-propa~oate as an oily residue;

methyl 2, 4-dichloro--(2 , 4-dichlorophenyl)benzenebutanoate as an oily residue;

._ !

methyl 4-chloro-a-(4-chlorophenyl)benzenebutanoate; bp. 175-178C
at 0.1 mm. pressure;

methyl 2, 4-dichloro-x-~-(2-naphthalenyloxy)propy~7benzeneacetate;
mp. 6 9 . 7 C ;

methyl 4-chloro-a-(4-methylphenyl)benzenebutanoate as an oily residue;

methyl a-(4-bromophenyl)-2-methoxybenzenebutanoate; bp. 178-185C
at 0.1 mm. pressure;

methyl a-(4-bromophenyl)-4-chlorobenzenebutanoate; bp. 177-180C
at 0.1 mm. pressure;

methyl 4-chloro-a-(4-fluoropher~yl)benzenebutanoate as an oily residue;

methyl a-(4-fluorophenyl)-4-methylbenzenebutanoate as a residue;

methyl 4-bromo--(2-chlorophenyl)benzenebutanoate as an oily residue;

me~yl 4-bromo-a-(4-bromophenyl)benzenebuPnoate as an oily residue;

methyl a-~-(4-bsomophenoxy)ethyl7-2, 4-dichlorobe~zeneacetate as a residue;

methyl 2, 4-dichloro-a-~-(3, 5-dichlorophenoxy)propy~benzeneacetate as a residue;

methyl 2, 4-dichloro-a-~-(4-chloro-3-methylphenoxy)propy~7benzene-acetate as a residue;

methyl -~-(2-bromophenoxy)propy~7-2,4-dichlorobenzeneacetate as a residue;

methyl 2, 4-dichloro-a-~-(4-chloro-2-methylphenoxy)propy~7benzene-acetate as an oily residue;

4~

~nethyl 2, 4-dichloro-a-~-(2, 4-dichloro-6-methylphenoxy)propy~7-benzeneacetate as a residue;

methyl o~-~-(2-bromo-4-methylphenoxy)propy~.7-2, 4-dichloroben7ene-acetate as a residue;

methyl 2, 4-dichloro-a-C-(3-chloro-r, 1 '-bipheny~7-4-yloxy)propy~7-benzeneacetate; and methyl 2, 4-dichloro-a-~-(2, 4, 6-tribromophenoxy)propy~7benzene-acetate as an oily residue.

EXAMPLE XII

To a stirred mixture of 2Z parts of methyl 2, 4-dichloro-benzeneacetate and 135 parts of N, N-dimethylformamide are added 3. 1 parts of sodium hydride dispersion 78 % while nitrogen gas is intro-duced. The whole is stirred till foaming has ceased and cooled in an ice-bath. Then there are added dropwise 16 parts of iodomethane. Upon completion, st irring is continued for 3 hours at room temperature. The reaction mixture is poured onto water and the product is extracted with 2, 2'-oxybispropane. The extract is washed with water, dried, filtered and e~raporated, yielding 20 parts (80%) of methyl 2,4-dichloro--methylbenzeneacetate as a residue.

; - ~

To a stirred mixture of 22 parts of methyl 2, 4-dichloro-benzeneacetate and 135 parts -of N, N-dimethylformamide are added 3. 1 parts of a sodium hydride dispersion 78 % while nitrogen gas is intro-- duced. After stirring till foaming has ceased, there are added 15 parts of 2-bromopropane and the whole is stirred for 3 hours at room tempe-rature. The reaction m~xture is poured onto water and the product is ~ 3~-l~L;~

extracted twice with 2, 2'-oxybispropane. The combined extracts are washed with water, dried, filtered and evaporated, yielding 24. 5 parts (94%) of methyl 2, 4-dichloro-a-~I-methylethyl)benzeneacetate as a residue.
.
To 140 parts of I, I '-oxybisethane are added 3 parts of lithium aluminium hydride. Then there is added dropwise a solution of 24.5 parts of methyl Z,4-dichloro--(1-methylethyl)benzeneacetate in 35 parts of 1, l'-oxybisethane while cooling in a water-bath. Upon completion, stirring is continued overnight at room temperature. There are added dropwise successively 3 parts of a sodium hydroxide solution 50% and 1 part of water, and the whole is stirred for one hour at room temperature. The mixture is filtered over hyno and the filter-cake is washed with 2, 2'-oxybispropane. The filtrate is evaporated, yielding 20. 5 parts (93. 5~0 ) of 2, 4-dichloro-,l3-(1-methylethyl)benzeneethanol as a residue.

EXAMPLE XI~

A mixture of 16.5 parts of methyl 2,4-dibromo--butyl-benzeneacetate, 11. 5 parts of lithium iodide dihydrate and 180 parts of acetonitrile is stirred till all solid enters solution. Then there are added portionwise 3. 6 parts of sodium borohydride. Upon completion, the whole is heated to reflux and stirring is continued overnight at reflux temperature. After cooling, the reaction mixture is acidif;ed with a diluted hydrochloric acid solution and poured onto water. The product is extracted with 2, 2'-oxybispropane. The extract is washed with water, dried, filtered and evaporated, yielding 15 parts (100%) of 2, 4-dibromo- 13-butylbenzeneethanol as a residue.

1133'~

EXAMPLE XY

Following the procedure of Example XIV and using an equivalent amount of an appropriate methyl ester as a starting material the following alcohols are obtairned as a residue:

~-(3-butenyl)-Z, 4-dichlorobenzeneethanol;

Z, 4-dichloro-~3-methylbenzeneethanol;

2, 4-dichloro-,B_(cyclohexylmethyl)benzeneethanol;

2, 4-dichloro- ~-(2 -cyclopentylethyl)benæ neethanol;

2, 4-dichloro-~-(Z-cyclohexyletl:lyl)benzeneethanol;

~-(2, 4-dichlorophenyl)-~, 1 '-bipheny~7-4-propanol;

2, 4-dichloso-,3-(2, 4-dichlorophenyl)benzenebutanol;

4-chloro-,3-(4-chlorophenyl)ben~ nebutanol;

4-chloro- ~-(4-methylphenyl)benzenebutanol;

~-(4-bromophenyl) -2 -methoxybenzenebut~nol;

~-(4-bromophenyl)-4-chlorobenzenebutanol;

4-chloro-~-(4-fluorcrphenyl)benzenebutanol;

~-(4-nuorophenyl)-4-methylbenzenebutanol 4-bromo -13-(2 -chlorophenyl)benzenebutanol;

4-bromo - ~-(4-bromophenyl)benz enebutanol;

1~33~9'~

(4-bromophenoxy)ethy.~7-2, 4-dichlorobenzeneethanol;

2,4-dichloro-~-~-(3, 5-dichlorophenoxy)propy~7benzeneethanol;

~-r-(2-bromophenoxy)propy~7-2, 4-dichlorobenzeneethanol;

2, 4-dichloro-~-~-(4-chloro-3-methyl`phenoxy)propy~7benzeneethanol;

Z, 4-dichloro-~-~-(4-chloro-2-methylphenoxy)propy~7benzeneethanol;

2, 4-dichloro-~-~-(2-naphthalenyloxy)propy~7benzeneetharlol;

~-~-(2-bromo-4-methylphenoxy)propyl7-2, 4-dichlorobenzeneethanol;

2, 4-dichloro-l3-~-(2, 4-dichloro-6-methylphenoxy)propy~7benzene-et~a3lol;

2, 4-dichloro-~-~-(3-chloro-~, 1 '-bipheny~7-4-yloxy)p~opy~;7benzene-ethanol; aud 2, 4-dichloro- B_~-(2, 4, 6 -tribromophenoxy)propy.~7benzeneethanol.

.. . . _ . . .. . . . . . .
EXAMPLE XVI

To a stirred and cooled (ice-bath) mixture of 22 parts of 2, 4-dichloro- 13-(cyclohexyln~ethyl)benzeneethanol and 50 parts of pyrid ne are added dropwise 8. 8 parts of methanesulfonyl chloride. Upon com-pletion, stirring is continued for 3 hours at room temperature. The reaction mixture is poured onto water and the product is extracte~l twice with trichloromethane. The combined extracts are washed twice with a diluted hydroc~loric acid solution and once with water, dried, filtered and evaporated. The residue is crystallized from 2, 2'-oxybispropane, yielding 16.5 parts of 3-cyclohexyl-2-(2,4-dichlorophenyl)propyl methanesulfonate; mp. 1 Q5 . 1 C .

_ 3 ~7--EXA~MPLE XVII

Following the procedure of Example X~I the following methanesulfonates are prepared starting from the co-responding alcohols:

2-(2,4-dichlorophenyl)-5-hexenyl methanesulfonate as a residue;

2-(2,4-dichlorophenyl)propyl methanesulfonate as a residue;

2 -(2, 4-dichlorophenyl)- 3 -methylbutyl methanesulfonate as a residuei 2-(2,4-dibromophenyl)hexyl methanesulfonate as a residue;

4-cyclopentyl _2 -(2, 4-dichlorophenyl)butyl methanesulfonate; mp. 6i . 4C;

4-cyclohexyl-2 -(2, 4-dichlorophenyl)butyl methanesulfonate; mp.
44. 4C;

3-(~ -bipheny~7-4-yl)-2-(2, 4-dichlorophenyl)propyl methanesulfonate as an oily residue;

2,4-bis(2,4-dichlorophenyl)butyl methanesulfonate as an oily residu2;

2, 4-pis(4-chlorophenyl)butyl methanesulfonate as a residue;

4-~4-chlorophenyl)-2-(4-methylphenyl)butyl methanesulfonate as an oily residue;

2-(4-bromophenyl)-4-(Z-methoxyphenyl)butyl methanesulfonate as an oily residue;

2-(4-bromophenyl)-4-(4-chlorophenyl)butyl methanesulfonate as an oily residue;

_ 3~-~1334~9'~

- 4-(4-chlorophenyl)-2-(4-fluorophenyl)butyl methanesulfonate as an oily residue;

2-(4-fluorophenyl)-4-(4-methylphenyl)butyl methanesulfonate as an oily residue; and 4-(4-brornophenyl)-2-(2-chlorophenyl)butyl methanesulfonate as an oily residue.

EXAMPLE XVIII

A mixture of 30. 4 parts of ,B_~-(4-bromophenoxy)ethy~7_ 2,4-dichlorobenzeneethanol, 11.5 parts of methanesulfonyl chloride 100 parts of pyridine and 70 parts of 2, 2'-oxybispropane is stirred overnight at room temperature. The reaction mixture is poured onto water and the product is extracted twice with 2, 2'-oxybispropane.
The combined extracts are washed successively with a diluted hydro-chloric acid solution and twice with water, dried, filtered and evapo-rated, yielding 34 parts of 4-(4-bromophenoxy)-2-~2, 4-dichlorophenyl)-butyl methanesulfonate as a residue.

EXAMPLE XIX

Following the procedure of }~;xample X~III the following methanesulfonates are prepared starting from the corresponding alcohols:

5-(3, 5-dichlorophenoxy)-2-(2, 4-dichlorophenyl)pentyl meth nesulfonate as a residue;

5-(2-bromophenoxy) ~2-(2, 4-dichlorophenyl)pentyl methanesulfonate as a residue;

3 9 ~

5-(4-chloro-3-methylphenoxy)-2--(2,4-dichlorophenyl)pentyl methane-sulfonate as a residue;

2-(2, 4-dichlorophenyl)-5-(2-naphthalenyloxy)pentyl methanesulfonate as a residue;

5-(4-chloro-2-methylphenoxy)-2-(2, 4-dichlorophenyl)pentyl methane-sulfonate as a residue;

5 -(2 -bromo-4-methylphenoxy) -2 -(2, 4-dichlorophenyl)pe~tyl methane-sulfonate as an oily residue;

5-(2, 4-dichloro-6-methylphenoxy)-2-(2, 4-dichlorophenyl)pentyl methanesulfonate as a residue;

5-~2-chloro-~, 1 '-bipheny.~7-4-yloxy)-2-(2, 4-dichlorophenyl)pentyl methanesulfonate as a residue;

2,4-bis(4-bromophenyl)butyl methanesulfonate as an oily residue; and 2-(2, 4-dichlorophenyl)-5-(2, 4, 6-tri}iromophenoxy)pentyl methane-sulfonate as a residue.

EXA MPLE XX

To a stirred suspension of 3. 4 parts of a sodium hydride dis-persion ?8 % in 90 parts of N, N-dimethylformamide are added portion-wise, during a 5 minutes-period, 6. 9 parts of lH-l, 2, 4-triazole. After stirring for 10 minutes at room temperature, there are added 19.1 parts of 4-chloro--(chloromethyl)benzeneme~ol. The whole is stirsed and refluxed for 8 hours. The reaction mixture is cooled and poured onto water. The product is extracted with dichloromethane. The extract is washed with water, dried, filtered and evaporated. The r esidue is tri-turated in Z, 2'-oxybispropane. The product is filtered off and crystal-lized fxom methylbenzene, yielding 17. 3 parts (77%) of a-(4-chloro-phenyl)-lH-1,2,4-triazole-1-ethanol; mp. 119C.

.40 -~3~

EXA MPLE XXI

To a stirred mixture of I4 parts of lH-1,2,4-triazole and 225 parts of N, N-dimethylformamide are added 6.2 parts of a sodium hydride dispersion 78 %. When foaming has ceased, there are added 19.5 parts of 2-(2, 4-dichlorophenyl)propyl methanesulfonate and stirring i8 continue~d for 6 hours at reflux. The reaction mixture is cooled, poured onto water and the product is extracted twice with 2,2'-oxybis-propane. The combined extracts are washed with water, dried, filtered and evaporated. The residue is crystallized from petroleumether. The product is filtered off and dried, yielding 10. 2 parts (58 %) of 1-~-(2, 4-dichlorophenyl)propy~- lH - 1; 2, 4-triazole; mp. 79. 5 C

EXAMPLE XXII

To a stirred mixture of 16 parts of lH-1,2,4-triazole in Z25 parts of N, N-dimethylforrr.amide are added 6.8 parts of a sodium hydride dispersion 78 % and the whole is stirred till foaming has ceased.
Then there are added 23. 5 parts of 2-(2, 4-dichlorophenyl)-3-methyl-butyl methane~ulfonate and stirring is continued for 24 hours at reflux temperature. The reaction mixture is cooled and poured onto water. The product i~ extracted twice with 2,2'-oxybispropane. The combined ex-tracts are washed with water, dried, filtered and evaporated. The residue is purified by col~nn-chromatography over silica gel using a mixture of trichloromethane and methanol (98 :2 by volume) as eluent.
The pure ractions are collected and the eluent is evaporated. The residue is converted into the nitrate salt in 2,2'-oxybispropane. The salt is filtered off and crystallized from a mixture of 4-methyl_2_ pentanone and 2,2'-oxybispropane, yielding 18.4 parts (70%) of -(2, 4-dichlorophenyl)-3-methylbuty~7-lH-1,2,4-triazole nitrate;
mp. 147.1~C.

_41 --1~3~

EXAMPLE XXIII

Following the procedure of Example XXII and usingan equi-valent amount of an appropriate methanesulfonate in place of the 2-(2,4-dichlorophenyl)-3-methylbutyl methanesulfonate used therein, the following triazoles and triazole nitrate salts are prepared:

1 -r-(2,4-dichlorophenyl)buty~7-lH-1,2,4-triazole; mp. 70.2C;

-(2,4-dichlorophenyl)penty~7-lH-1,2,4-triazole; mp 62.7C;

1 -~-(2,4-dibromophenyl)hexy~7-lH-1,2,4-triazole nitrate; mp.
141.7C;

1-~-(2,4-dichlorophenyl)-3-methylpenty~7-lH-1,2,4-triazole nitrate;
mp. 116.6C;

2,4-dichlorophenyl)-4-methylpenty~7-lH-1,2,4-triazole nitrate;
mp. 146.8C;

l-~-t2,4-dichlorophenyl)hepty.~7-lH-1,2,4-triazole nitrate; mp.
144.6C;

1-~-(2,4-dichlorophenyl)decy.a7-lH-1,2,4-triazole nitrate; mp. 116.6C;

1 -~-cyclopentyl-2-(2,4-dichlorophenyl)ethy~7-lH-1,2,4-triazole nitrate;
mp. 149.2C;

cycl~hexyl-2-(2,4-dichl~rophenyl)ethy.~.7-lH-1,2,4-triazole;
mp. 79.2C;

I -C-cyclohexyl-2-(2,4-dichlorophenyl)propyl7-lH-1,2,4-triazole nitrate hesnihydrate; mp. 124.3 C;

-cyclohexyl-Z-(2,4-dichlorophenyl)buty~7-lH-1,2,4-triazole;
mp. 96.5C;

1-~-(2, 4-dichlorophenyl)-4-penteny~7-lH-1, 2, 4-triazole nitrate;
mp. 139. 7C; and 1-~-(2, 4-dichlorophenyl)-5-hexeny~-lH-1, 2, 4-triazole mononitrate;
mp. 114. 8C.

To a stirred mixture of 3.8 parts of a sodium hyd.ide dis-persion 78% and 90 parts of N,N-dimethylformamide is added dropwise a solution of 21 parts of 2, 4-bis(4-chlorophenyl)butyl methanesulfonate in 45 parts of N,N-dimethylformamide. Afte. stirring for 15 minutes at room temperature, there is added a solution of 7. 6 parts of lH-1,2,4-triazole in 45 parts of N,N-dimethylformamide. The whole is heated slowly to 100C and stirring is continued for 2 hours at 100C. The reaction mixture is poured onto water and the product i8 extracted with 1, 1 '-oxybisethane. The extract is washed with water, dried, f~ltered and e~aporated. The oily residue is purified by column-chromatography over silica gel using a mixture of tric~loromethane and methanol (97. 5:2. 5 by volume) as eluent. The pure fractions are col-lected and the eluent is e~raporated. The oily residue is converted into the hydrochloride salt in 2, 2'-oxybi~propane. The salt is filtered off and crystallized from a mixture of methanol and 2,2'-oxybispropane, yielding 7 parts (32. 5q'o) of 1-,~, 4-bis(4-chlorophenyl)buty~7-lH-1, 2, 4-triazole hydrochloAde; rrlp. 173 . 4 C .

EXAMPLE XXV

Following the procedure of Example XXIV and using an equi-valent arslount of an appropriate methanesulfonate in place of the 2, 4-bis(4-chlorophenyl)butyl methanesul~onate, the following tTiazoles and triazole hydrochloride salts are prepared:
~ 3 _ ~33~

. 1 '-bipheny~7-4-yl)-2-(2, 4-dichlorophenyl)propy~-1, Z, 4-triazole hydrochloride; mp. I 75 . 5 C;

1 -~-t4-chlorophenyl)-2-(4-methylphenyl)buty~7-lH-I, 2, 4-triazole hydrochloride; mp. 170C;

1-~-(4-bromophenyl)-4-(2-methoxyphenyl)buty~7-lH-1, ~, 4-triazole hydrochloride; mp 15 3 . 2 C;

1 -~-(4-bromophenyl)-4-(4-ch~orophenyl)buty~7-lH-1, 2, 4-triazole;
mp. 87. 6CC;

1 - /~-(4-chlorophenyl) -2 -(4-fluorophenyl)buty~- l H-1, 2, 4-triazole hydrochloride; mp. 171.8C;

1-~-(4-fluorophenyl)-4-(4-methylphenyl)buty~J-lH-1, 2, 4-triazole hydrochloride; mp. 128 . 6 C;

;
1-r-(4-bromophenyl)-2-(2-chlorophenyl)butyi7-lH-1, 2,.4-triazole hydrochloride; mp. 142.6C; and - 15 1-~, 4-bis(4-bromophenyl)buty~7-lH-1, 2, 4-triazole hydrochloride;
mp. 163C.

EXAMPLE XXVI

A mixture of 6.9 parts of lH-1,2,4-triazole, 3.4 parts of a sodit~m hydride dispersion 78 % and 90 parts of N,N-dimethylform_ amide is stirred for 10 minutes at room temperature. Then these is added a solution of 19. 9 parts of 5-(2-bromo-4-methylphenoxy)-2-(2, 4-dichlorophenyl)pentyl methanesulfonate in 45 parts of N, N-dimet hyl-formamide. Stirr~g is continued for 2 hours at 100C. The reactio~
mixture is allowed to cool to room temperature and poured onto water.
The product is extracted twice with 1, 1 '-oxybisethane. The combined extracts are washed with water and acidified with a concentrated nitric _44--1~13;~

acid solution. The for~ned nitrate salt i~ filtered off and crystallized from a mi~cture of acetonitrile and 2,2' -oxybispropane, yielding 13.3 parts (64% ) of 1-~-(2-bromo-4-methylphenoxy)-2-(2,4-dichlorophenyl)-penty~7- 1 H - 1,2,4-triazole nitrate; mp. 119.6 C .

EXAMPLE XXVII

Following the procedure of Example XXVI the following triazole nitrate salts are prepared st rting from lH-1,2,4-triazole and an appropriate methanesulfonate:

1 -~-(3,5-dichlorophenoxy)-2-(2,4-dichlorophenyl)penty~-lH-1,2,4-triazole nitrate; mp. 145.3C;

-(4-bromophenoxy)-2-(2,4-dichlorophenyl)buty~7-lH-1,2,4-triazole nitrate; mp. 144.6 C;

1 -~-(2-bromophenoxy)-2-(Z,4-dichlorophenyl)penty~7-lH-1,2,4-triazole nitrate; mp. 123.2-C;

1 -~-(2,4-dichlorophenyl)-5-(2-naphthalenyloxy)pe~ty~-lH-1,2,4-triazole nitrate; mp. 136.8 C;

1-~-(4-chloro-3-methylphenoxy)-2-(Z,4-dichlorophenyl)penty~7-1H-1,2,4-triazole nitrate; mp. 140 a C;

1 -C-(4-chloro -2 -methylphenoxy) -Z -(2,4 -dichlorophenyl)penty~7- 1 H -- 20 1,2,4-triazole nitrate; mp. 123.1C;

1-~-(2,4_dichloro-6-methylphenoxy)-2-(2,4-dichloropher~yl)penty~
lH-l,2, 4-triazole nitrate; mp. 153. 4C;

(3-chloro-~,1 '-bipheny~7-4-yloxy)-2-(Z,4-dichlorophe~yl)penty~7-l H - 1,2,4-triazole nitrate; mp. 135.3 C; and (2, 4-dichlorophenyl)-5-(2, 4, 6-tribromophenoxy)pentyi7-1H-l, 2, 4-triazole nitrate; mp. 166 . 5 C:

EXA~PLE XXVIII

To a stirred sodium methoxide solution, previously prepared starting from 3. 9 parts of sodium in 40 parts of ~nethanol,is added a mixture of 12 parts of lH-1,2,4-triazole and225 parts of N,N-dimethyl-formamide. The methanol is distilled off till an internal temperature o 150C is reached. After cooling to 100C, there are added 18.5 parts of 2-(2,4-dichlorophenyl)hexyl methanesulfonate and stirring at 100C is continued for 2 hours. The reaction mixture is cooled, poured onto water and the product is extracted three times with 2, 2'-oxybispropane. The combined extracts are ~ashed with water, dried, filtered and evaporated.
The residue is purified by colu~s~n-chromatography over silica gel using trichloromethane as eluent. The pure fractions are collected and the ; 15 eluent i5 evaporated. The residue is converted into the nitrate salt 2, 2'-oxybispropane and petroleumether. The salt is filtered off and crystallized from a mixture of 2-propanone, 2,2'-oxybispropane ar~d petroleumether, yiel~;ng 11.6 parts (56~o) of 1-r-(Z,4-dichlorophenyl)-hexy~7-1H-1, 2, 4-triazole nitrate; mp. 128. 3C.

EXAMPLE XXIX

Following the procedure of Example XX~III there are prepa-red: -1 -~-cyclopentyl-2-(2, 4-dichloropheryl)buty~7-lH-1, 2, 4-triazole;
mp. 71-C, by the reaction of lH-1,2,4-triazole with 4-cyclopentyl-Z-(2,4-dichlorophenyl)butyl methanesulfonate; and 1-~, 4-bis(2, 4-dichlorophenyl)buty~7-lH-1, 2, 4-triazole hydrochloride mp. 158. 7C, by the reaction of lH-l, 2, 4-tTiazole with 2,4-bis(2, 4-dichlorophenyl)butyl methanesul~onate.

EXAMPLE XXX

To a stirred sodium methoxide solution, prepared starting from 1. 6 parts of sodium in 56 parts of methanol, are added 4. 8 parts of lH-1,2,4-triazole. 40 Parts of methanol are distilled off at normal pressure. After the addition of 80 parts of 4-methyl-2-pentanone, an-other 28 parts of solveslt are distilled off. Then there are added 22 parts of 3 -(4-chlorophenyl) -2 -(2, 4-dichlorophenyl)propyl methanesulfonate and 90 parts of N,N-dimethylformamide and the whole is stirred and refluxed overnight. The reaction mixture is allowed to cooi to room temperature and poured onto water. The product is extracted twice with 2, 2'-oxybispropane. The combined extracts are washed twice with water and an excess of a concentrated nitric acid solution i9 added.
The formed nitrate salt is filtered off and crystallized from 4-methyl-2-pentanone, yielding 6. 6 parts (27q'o) of 1 -r-(4-chlorophenyl)-2-(2, 4-dichlorophenyl)propy~7-lH-l, 2, 4-triazole ni~rate; mp. 174. 8 C.

EXA MPLE XXXI

Following the procedure of Example XXX there is prepared1-~-(2-bromophenyl)-2-(2J 4-dichlorophenyl)propy~;7-lH-1, 2, 4-triazole nitrate; mp. 168. 4C, by the reaction of 1H-l, Z, 4-triazole with 3-(2-bromophenyl)-2-(2, 4-dichlorophenyl)propyl methanesulfonate.

~3~

EXAMPLE XXXII

A mixture of 5 . Z parts of t~-(2, 4-dichlorophenyl)- 1 H- 1, 2, 4-triazole-l-ethanol, 45 parts of N,N-dimethylformamide and 45 parts of benzene is stirred till all solid enters solution. After cooling in an ice-bath, there is added portionwise 1 part of a sodium hydride disper-sion 78%and the whole is stirred till gas-evolution has ceased. Then there are added 2. 75 parts of l-bromopropane and stirring is continued first for 2 hours while cooling in an ice-bath and further overnight at room ternperature. The reaction mixture is poured onto ice-water and the product is extracted with 1, 1 '-oxybisethane. The extract is washed with water, dried, filtered and evaporated. The oily residue is purified by column-chromatography over silica gel using a mixture of tri-chloromethane and methanol (95 :5 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The oily residue i8 converted into the nitrate salt in 2, 2'-oxybispropane. The salt is filtered off and crysta~lized from a mixture of 2-propanol and 2, 2'-oxybispropane, yielding 2. 5 parts (34. 4%) of 1-~-(2, 4-dichlorophenyl)-2-propo~yethyy-lH-1, 2, 4-triazole nitrate; mp. 140C.

EXAMPLE XXXLlI

Following the procedure of Example XXXII and using equi-~ralent amounts of the appropriate starting materials, the following compounds are prepared:

l -L---~2, 4-dichlorophenyl)-2-ethoxyethy.~;7-lH-1, 2, 4-triazole nitrate;
mp. 1 36 . 7 C ;

1 -~-butoxy-2 -(2, 4-dichlorophenyl)ethyD-1 H- 1, 2, 4 -triazole nitrate;
mp. 148. 1C;

(2, 4-dichlorophenyl)-2-(hexyloxy)ethy~7-lH-1, 2, 4-triazole nitrate;
mp. 140. 1C;

1~33~

l-C-(2, 4-dichlor,ophe~yl)-2-(heptyloxy)ethy~7-lH-1, 2, 4-triazole nitrate;
- mp. 139.2C; and 1 -C-(2, 4-dichlorophenyl)-2-(Z-propenyloxy)ethy~7-lH-1, 2, 4-triazole nitrate; mp. 1 3Z. 5 C .

EXAMPLE XXXIV

A mixture of 4.5 parts of c~-(4-chlorophenyl)-lH-1,2,4-triazole-l-ethanol, 50 parts of dimethyl suIfoxide and 45 parts of benzene is stirred till all solid enters solution. Then there is added 1 part of a sodium hydride dispersion 78 % and stirring is cont~ued till foaming has ceased. Aftèr stirring and heating for one hour at 40-50C, the mixture is cooled to room temperature and 5. 4 parts of bromoethane are added. The whole is stirred over~ght at room tem-perature, poured onto ice-water and the product is extracted with 1, 1'-oxybisethane. The extract i9 washed with water, dried, filtered and eva-porated. The oily residue i3 purified by column-chromatography over . silica gel using a mixture of trichloromethane and met~nol (95:5 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The oily residue is converted into the nitrate salt in 2, 2' -oxybispropane and hexane (1:5 by voll~me). The salt is filtered off and crystallized from a mixture of 2-propanol and hexane, yielding 3 parts (47. 6 %) of 1 -~-(4-chlorophenyl)-2-ethoxyethy~7-1H-1, 2, 4-triazole mononitrate; mp. 118 . 7 C .

EXAMPLE XXXV

Follo~ing the procedure of Example XXXIV and using equivalent amounts of the appropriate starting mate,ials the following compounds are prepared:

1~3~92 1 -~2-butoxy-2-(4-chlorophenyl)ethy~7-lH-1, 2, 4-triazole mononitrate;
mp. 1 0 7 . 1 C ; - -1-~-(2, 4-dichlorophenyl)-2-(pentyloxy)ethy~7-lH-I, 2, 4-triazole nitrate; mp 149C;

1 -~-(4-chlorophenyl)-2-(pentyloxy)ethy.~7-lH-1, 2, 4-triazole mono-nitrate; mp. 110.5C;

1-~-(4-chlorophenyl)-2-(hexyloxy)ethy~7-lH-I, 2, 4-triazole mono-nitrate; mp. 1 17. 6 C; and 1 - ~-(4-chlorophenyl)-2 -(heptyloxy)ethy~7- I H -1, 2, 4-triazole mono -nitrate; mp. 118.3C.

EXA MPLE XXXVI

A rn~xture of 5. 2 parts of a-(2, 4-dichloroph'enyl)-lH-1, 2, 4-triazole-l-ethanol, 50 parts of dirnethyl sulfoxide and 45 parts of ben-zene is stirred till all solid enters solution. Then there is added 1 part of a sodium hydride dispersion 78 % and stirring is continued till gas-evolution has ceased. After stirring for one hour at 40-50C, there are added 2. 3 parts of 3-chloro-1-prop~e. The whole is stirred overnight at room temperature. The reaction mixture is poured onto ice-water and the product is extracted with 1, 1 '-oxybisethane. The extract is washed with water, dried, filtered and evaporated. The oily residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (95 :5 by volume) as eluent. The pure fractions are collected and the elue~t is evaporated. Upon standing overnight at room temperature, the residue soli~;fies. The product is 2~ filtered off and crystallized from 2, 2'-oxybispropane, yielding 2 parts (33. 8 %) of 1-~-(2, 4-dichlorophenyl)-2-(2-propynyIoxy)ethy~7-lH-1, 2, 4-triazole; mp. 84C.

1~3,~49Z

EXAMPLE XXXVII

A mixture of 5. 2 parts of c~-(2, 4-dichlorophenyl)-1H-1, 2, 4-triazole-l-ethanol, 50 parts of dimethyl sulfoxide and 45 parts o benzene i8 stirred till all solid enters solution. Then there is added one part of a sodium hydride dispersion 78 %. After foaming has ceased, stirring is continued for one hour at 40-50C. 3. 8 Parts of dimethyl sulfate are added and the whole is stirred overnight at room temperature. The reaction mixture is poured onto ice-water and the product is extracted with l,l'-oxybisethane. The extract is washedwithwater, dried, filtered and evaporated. The oily residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (95:
5 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The oily residue is converted into the nitrate salt in 2, 2'-oxybispropane. The salt is filtered off and crystallized from a mixture of 2-propanol and 2, 2'-oxybispropane, yielding 3 part9 (44. 7%) of 1-/~-(2, 4-dichIorophenyl)-2-methoxyethy--~7-lH-1, 2, 4-triazole nitrate;
mp. 145. 7C.

EXAMPLE XXXVIII

A mixture of 3.2 parts of -(2~4-dirhlorophenyl)-lH-l~2~4-triazole-1-ethanol nitrate, 2. 4 parts of 1-chloro-2-(chloromethyl)ben-zene, 1. 5 parts of a sodium hydride dispersion 50%, 70 parts of di-methyl sulfoxide and 63 parts of berLzene is stirred for 2. 50 hours at room tempesature. Water is added and the product is extracted twice with 2, 2'-oxybispropane. The extract is washed twice with water and the solvent is removed in vacuo. The residue is crystallized from 2, 2'-oxybispropane, yiel~ing 3 parts of 1-~.2-~2-chlorophenyl)methox~7_2_ (2, 4-dichlorophenyl)ethyl ~ -lH-1, 2, 4-triazole; mp. 106. 4C

' EXAMPLE XXXIX

Following the procedure of Example XXXVIII and using equi-valent amounts of the appropriate starting materials, the following com-pounds are prepared in free base form or in the form of a nitrate salt after treatment of the free base with nitric acid.

1- ~Z-~4-chlorophenyl)methox~-Z-(2, 4-dichlorophenyl)ethyl~_1H-1, 2, 4-triazole mononitrate; mp. 164, 9C;

2 -(2, 4-dichlorophenyl) -2 - ~2 ,-4-dichlorophenyl)methoxy7ethyl}- lH -1,2,4-triazole mononitrate; mp. 170~C; and 1 - ~ 2 -(2, 4-dichlorophenyl)-2 -~r2, 6 -dichlorophenyl)methoxy7ethyl}- lH-- 1,2,4-triazole; mp. 126.3C.

- ~:~AMPLE XL

Following the proc'edure of Example X there is prepared methyl 2, 4-dibromobenzeneacetate; bp. 105 -110 C at 0 . 1 mm, pressure, starting from 2, 4-dibromobenzeneacetonitrile.

EXAMPLE XLI

Following the procedure of Example XIII and using equi-valent amounts of the appropriate starting materials the following compoLnds are prepared:

2, 4-dibromo-~-(2 _methylpropyl~benzeneethanol as a residue;

2, A -dibromo-~'3-(1-methylethyl)benzeneetha~ol as a residue; and Z,4-dibromo-~3-(I-methylpropyl)benzeneethanol a~ a residue.

4L9~2 XAMPLE XLII
.
Following the procedure of Example XVI and using equi-valent amounts of the appropriate starting materialq there are prepared:

r-(2, 4-dibromophenyl)-4-methylpenty~7methanesulfonate a~ a residue;

C-(2,4-dibromophenyl)-3-methylbuty~methanesulfonate as a residue; asld ~-(Z,4-dibromophenyl)-3-methylpenty~7 methanesulfonate as a 1 0 residue.

EXAMPLE XLIII

Following the procedure of Example XXXII there are prepared:

1 -~-(4-chlorophenyl)-2-(2-methylpropo~z:y)ethy~7~-lH-1, 2, 4-triazole mononitrate; mp. 114. 5 C; and 1-~-(2, 4-dichlorophenyl)-2-(2-methylpropoxy)ethy~7-lH-1, 2, 4-triazole mononitrate; mp. 148 C

by the reaction of (2-methylpropyl) methanesulfonate with respectively c~-(4-chlorophenyl)-IH-I, 2, 4-triazole-I -ethanol and a-(2, 4-dichloro-phenyl)-lH-I, 2, 4-triazole-I -ethanol.

EXAMPLE XLIV

Following the procedure of Example XXXIV there i~ pre-pared 1 -~-(4-chlorophenyl)-Z-(2-propenyloxy)ethy~7-lH-I, 2, 4-tria-zole mononitrate;mp. 100. 4C, by the reaction of cc-(4-chlorophenyl)-~3~g~X

lH-1, 2, 4-triazole-I-ethanol with 3-bromo-1 -propene.

EXAMPLE XLV

Following the procedure of Example XXII and using equivalent amounts of the appropriate starting materialq the following compounds are obtained:

1 -C-(2, 4-dibromophenyl)-4-methylpenty~7-lH-1, 2, 4-triazole mononitrate; mp. 153.6C;

1 -C-(2, 4-dibromophenyl)-3-methylbuty~7-lH-1, Z, 4-triazole mononitrate; mp. 142 . 9 C;

1 - r-(4-chlorophenyl)-2-(1 -methylethoxy)ethy~.7-1H-1, 2, 4-triazole mononitrate; mp. 135 . 3 C;

1-~-(2, 4-dichlorophenyl)-2-(1 -methylethoxy)ethyy-lH-I, 2, 4-tria-zole mononitrate; mp. 146.1C; and 1-~-(2, 4-dibromophenyl)-3-methylpenty~-lH-1, 2, 4-triazole mononitrate; mp. 131. 8C.

_;4_

Claims (23)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

I. A chemical compound selected from the group con-sisting of a 1H-1,2,4-triazole derivative having the formula:

and the physiologically acceptable acid addition salts thereof, wherein:

Ar is a member selected from the group consisting of phenyl, mono-, di- and tri-halophenyl, lower alkylphenyl lower alkyloxy-phenyl, nitrophenyl, cyanophenyl and trifluoromethylphenyl;
and R is a member selected from the group consisting of alkyl having from

1 to 10 carbon atoms, cycloalkyl, cycloalkyl-lower alkyl, lower alkenyl, aryl-lower alkyl, aryloxy-lower alkyl, said aryl being selected from the group consisting of phenyl, naphthalenyl and substituted phenyl, wherein said substituted phenyl is phenyl having from l to 3 substituents independently selected from the group consisting of halo, lower alkyl, lower alkyloxy, cyano, nitro and phenyl: provided that when more than l substituents are present only 1 thereof may be selected from the group consisting of cyano, nitro and phenyl.

2. A compound selected from the group consisting of 1-?2-(2,4-dichlorophenyl)-3-methylbutyl?-1H-1,2,4-triazolee and the physiologically acceptable acid addition salts thereof.

3. A compound selected from the group consisting of 1-?2-(2,4-dichlorophenyl)-3-methylpentyl?-1H-1,2,4-triazole and the physiologically acceptable acid addition salts thereof.

4. A compound selected from the group consisting of 1-?2-(2,4-dichlorophenyl)-4-methylpentyl?-1H-1,2,4-triazole and the physiologically acceptable acid addition salts thereof.

5, A compound selected from the group consisting of 1-?2-(2,4-dichlorophenyl)hexyl?-1H-1,2,4-triazole and the physio-logically acceptable acid addition salts thereof.

6. A compound selected from the group consisting of 1-?4-(4-chlorophenyl)-2-(4-methylphenyl)butyl?-1H-1,2,4-triazole and the physiologically acceptable acid addition salts thereof.

7. A compound selected from the group consisting of 1-[4-(4-chlorophenyl)-2-(4-fluorophenyl)butyl]-1H-1,2,4-triazole and the physiologically acceptable acid addition salts thereof.

8. A compound selected from the group consisting of 1-[2-(2,4-dibromophenyl)hexyl]-1H-1,2 4-triazole and the physio-logically acceptable acid addition salts thereof.

9. A compound selected from the group consisting of 1-[2-(4-fluorophenyl)-4-(4-methylphenyl)butyl]-1H-1,2,4-triazole and the physiologically acceptable acid addition salts thereof.

10. A compound selected from the group consisting of 1-[2-(2,4-dichlorophenyl)heptyl]-1H-1,2,4-triazole and the physiologically acceptable acid addition salts thereof.

11. A compound selected from the group consisting of 1-[2-cyclohexyl-2-(2,4-dichlorophenyl)ethyl]-1H-1,2,4-triazole and the physiologically acceptable acid addition salts thereof.

12. A compound selected from the group consisting sisting of a 1H-1,2,4-triazole derivative having the formula and the physiologically acceptable acid addition salts thereof, wherein:

Ar' is selected from the group consisting of dichlorophenyl and dibromo-phenyl; and R' is selected from the group consisting of alkyl having from 1 to 8 carbon atoms, cycloalkyl and 2-propenyl.

13. A process for preparing a chemical compound selected from the group consisting of a 1H-1,2,4-triazole derivative having the formula:

(I) and the physiologically acceptable acid addition salts thereof, wherein:
Ar is a member selected from the group consisting of phenyl, mono-, di- and tri-halophenyl, lower alkylphenyl, lower alkyloxyphenyl, nitrophenyl, cyanophenyl and trifluoromethylphenyl; and R is a member selected from the group consisting of alkyl having from 1 to 10 carbon atoms, cycloalkyl, cycloalkyl-lower alkyl, lower alkenyl, aryl-lower alkyl, aryloxy-lower alkyl, said aryl being selected from the group consisting of phenyl, naphthalenyl and substituted phenyl, wherein said substituted phenyl is phenyl having from 1 to 3 substituents independently selected from the group consisting of halo, lower alkyl, lower alkyloxy, cyano, nitro and phenyl provided that when more than one substituent is present, only one thereof may be selected from the group consisting of cyano, nitro and phenyl, characterized by (a) heating a compound of the formula or an alkali metal salt thereof with a compound of the formula wherein X is methanesulfonyloxy or 4-methylbenzene sulfonyloxy; in a polar organic solvent, at reflux temperature in order to prepare a compound of the formula (I) and, if desired, preparing physiologically acceptable acid addition salts of the products of steps (a) and further, if desired, resolving and isolating optical isomers of said compounds of formula I.

14. A process for preparing 1-[2-(2,4-dichloro-phenyl)-3-methylbutyl]-1H-1,2,4-triazole or the physiologi-cally acceptable acid addition salts thereof, characterized by reacting the sodium salt of 1H-1,2,4-triazole with 2-(2,4-dichlorophenyl)-3-methyl-butylmethane sulfonate and, if desired, preparing a physiologically acceptable acid addition salt of the product thereof.

15. A process for preparing 1-[2-(2,4-di-chlorophenyl)-3-methylpentyl]-1H-1,2,4-triazole or the physiologically acceptable acid addition salts thereof, characterized by reacting the sodium salt of 1H-1,2,4-triazole with 2-(2,4-dichlorophenyl)-3-methyl-pentyl methanesulfonate and, if desired, preparing a physio-logically acceptable acid addition salt of the product thereof.

16. A process for preparing 1-[2-(2,4-dichloro-phenyl)-4-methylpentyl]-1H-1,2,4-triazole or the physio-logically acceptable acid addition salts thereof, character-ized by reacting the sodium salt of 1H-1,2,4-triazole with 2-(2,4-dichlorophenyl)-4-methylpentyl methanesulfonate and, if desired, preparing a physiologically acceptable acid addition salt of the product thereof.

17. A process for preparing 1-[2-(2,4-dichloro-phenyl)hexyl]-1H-1,2,4-triazole or the physiologically acceptable acid addition salts thereof, characterized by reacting the sodium salt of 1H-1,2,4-triazole with 2-(2,4-dichlorophenyl)hexylmethansulfonate and, if desired, preparing a physiologically acceptable acid addition salt of the product thereof.

18. A process for preparing 1-[4-(4-chloro-phenyl)-2-(4-methylphenyl)butyl]-1H-1,2,4-triazole or the physiologically acceptable acid addition salts thereof, characterized by reacting 4(4-chlorophenyl)-2-(4-methyl-phenyl)butyl methanesulfonate with 1H-1,2,4-triazole and, if desired, preparing a physiologically acceptable acid addition salt of the product thereof.

19 . A process for preparing 1-[4-(4-chloro-phenyl)-2-(4-fluorophenyl)butyl]-1H-1,2,4-triazole or the physiologically acceptable acid addition salts thereof, characterized by reacting 4-(4-chlorophenyl)-2-(4-fluoro-phenyl)butyl methanesulfonate with 1H-1,2,4-triazole and, if desired, preparing a physiologically acceptable acid addition salt of the product thereof.

20. A process for preparing 1-[2-(2,4-dibromo-phenyl)hexyl]-1H-1,2,4-triazole or the physiologically acceptable acid addition salts thereof, characterized by reacting the sodium salt of 1H-1,2,4-triazole with 2-(2,4-dibromophenyl)hexyl methanesulfonate and, if desired, pre-paring a physiologically acceptable acid addition salt of the product thereof.

21. A process for preparing 1-[2-(4-fluorophenyl)-4-(4-methylphenyl)butyl]-1H-1,2,4-triazole or the physio-logically acceptable acid addition salts thereof, charac-terized by reacting 2-(4-fluorophenyl)-4-(4-methylphenyl) butyl methanesulfonate with 1H-1,2,4-triazole and, if desired, preparing a physiologically acceptable acid addition salt of the product thereof.

22. A process for preparing 1-[2-(2,4-dichloro-phenyl)heptyl]-1H-1,2,-triazole or the physiologically acceptable acid addition salts thereof, characterized by reacting the sodium salt of 1H-1,2,4-triazole with 2(2,4-dichlorophenyl)heptyl methanesulfonate and, if desired, preparing a physiologically acceptable acid addition salt of the product thereof.

23. A process for preparing 1-[2-cyclohexyl-2-(2,4-dichlorophenyl)ethyl]-1H-1,2,4-triazole and the physiologically acceptable acid addition salts thereof, characterized by reacting the sodium salt of 1H-1,2,4-triazole with 2-cyclohexyl-2-(2,4-dichlorophenyl)ethyl methanesulfonate and, if desired, preparing a physiological-ly acceptable acid addition salt of the product thereof.