CH623813A5 - Process for the preparation of novel imidazole derivatives having an antifungal and antimicrobial action - Google Patents

Description

The present invention relates to processes for the preparation of new imidazole derivatives, namely new l- [ß- (R-thio) phenylethyl] imidazoles or new l- [ß- (R-sulfinyl) phenylethyl] - imidazoles and l- [ß- (R-sulfonyl) phenylethyl] imidazoles, their formulas in the formula:

r i i (/ vi ch-ch0-n n r1 - (J> I 2 1 1

xtv1 s (o) Jp j m

R ©

can be summarized, and their acid addition salts, wherein R is alkyl, alkenyl, aralkenyl, substituted aralkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aralkyl, substituted aralkyl, aryl or substituted aryl, the substituted aralkenyl or substituted aralkyl on the aryl radical being at least one of Halogen, lower alkyl, lower alkoxy,

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Trifluoromethyl, nitro and cyano bears selected substituents and the substituted aryl carries at least one substituent selected from halogen, lower alkyl, lower alkoxy, trifluoromethyl, nitro, amino, acylamino and cyano, wherein R1 furthermore represents hydrogen, halogen, lower alkyl, lower alkoxy, trifluoromethyl, nitro , Cyano, thiocyanato or a group of the formula:

-s (0) n

I.

R2

R 2 represents alkyl, cycloalkyl, aralkyl, substituted aralkyl, aryl or substituted aryl, the substituted aralkyl and the substituted aryl on the aryl radical bearing at least one substituent selected from halogen, lower alkyl, lower alkoxy, trifluoromethyl, nitro and cyano, and wherein m , n and p, which may be the same or different, represent 0, 1 or 2, where the value of m can only be greater than the value of n if R2 represents aryl or substituted aryl.

From U.S. Patent No. 3,717,655, compounds of the formula:

ar-ch-ch "-n n

I 2 L = J

x

I.

CfVn ar '

known, where X is -O- or -NH-, Ar u.a. Phenyl or phenyl substituted by at least one substituent selected from halogen, lower alkyl and lower alkoxy, Ar 'and the like. Phenyl or phenyl substituted by at least one substituent selected from halogen, lower alkyl, lower alkoxy, cyano, nitro and amino and n stands for 0.1 or 2. These compounds have an antifungal and antibacterial activity, but this is less than that of the compounds of the formula I.

The alkyl groups in the compounds of the formula I can contain 1 to 20 carbon atoms; Examples of such alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-heptyl, n-octyl, n-nonyl, n-dodecyl, n-octadecyl and the like . The term "lower alkyl" refers to an alkyl group containing 1 to 6 carbon atoms. The term "lower alkoxy" refers to groups of the formula lower alkyl-O-, wherein the lower alkyl substituent is as defined above. The cycloalkyl groups can contain 5 to 8 ring carbon atoms; Examples of such cycloalkyl groups are cyclopentyl, cyclohexyl, cycloheptyl and the like. Suitable cycloalkylalkyl groups are cycloalkyl groups as defined above which are bonded to an alkyl group having 1 to 3 carbon atoms, e.g. Cyclopentylpropyl, cyclohexylmethyl, cyclohexylethyl, cycloheptylmethyl and the like. The alkenyl groups can contain 2 to 12 carbon atoms; Examples of such alkyl groups are allyl, 2-hexenyl, 3-octenyl, 2-octenyl, 2-decenyl and the like. Suitable aralkenyl groups are alkenyl radicals having 2 to 4 carbon atoms to which a hydrocarbon group is attached which consists of one or more aromatic rings and contains 6 to 10 ring carbon atoms, e.g. 3-phenyl-2-propenyl, 4-phenyl-3-butenyl, styryl, 3-naphthyl-2-propenyl and the 3rd

5

in

15

20th

25th

30th

35

40

45

50

55

60

65

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same. The alkynyl groups can contain 2 to 12 carbon atoms; Examples of such alkynyl groups are 2-propynyl, 3-hexynyl, 2-octynyl and the like. Suitable aryl groups are hydrocarbon groups which consist of one or more aromatic rings and contain 6 to 10 ring carbon atoms, e.g. Phenyl or naphthyl. Suitable aralkyl groups are hydrocarbon groups whose alkyl radical contains 1 to 4 carbon atoms and whose aryl radical corresponds to the above definition. Representative examples of aralkyl groups are benzyl, 3-phenylpropyl and the like. Examples of acylamino groups are groups of the formula R-CO-NH- which contain up to 12 carbon atoms and in which R is methyl, ethyl, isopropyl, n-butyl, pen-

tyl, octyl or the like. Examples of halogen atoms are chlorine, fluorine and bromine. Suitable “acid addition salts” are salts which the compounds of the formula I with inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid and phosphoric acid and the like, or organic acids, such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, Malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, io methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like.

All compounds of the formula I have at least one chiral center, namely the carbon atom to which rs (0)

No

-Dog

-ch2-n

LJ

n

30th

are bound. Accordingly, the compounds of formula I can be prepared either in optically active form or as a racemic mixture. Unless otherwise stated, the compounds described in this description are all in the racemic form. However, the invention is not limited to the production of the racemic form, but is also intended to include the production of the individual optical isomers of the compounds of the formula I.

If desired, racemic intermediates or end products produced in the present description can be split into their optical antipodes by conventional methods known per se; such processes are e.g. in U.S. Patent Nos. 3,717,655 and 3,839,574. The splitting into the optical antipodes can, however, also be carried out by separating (e.g. fractional crystallization) the diastereomeric salts which are obtained by reacting e.g. racemic compounds of the formula I are formed with an optically active acid, or the diastereomeric esters which are formed by reacting the racemic alcoholic precursors of the 4Q compounds of the formula II with an optically active acid. Examples of such optically active acids are the optically active forms of camphor-10-sulfonic acid, a-bromocampher-3t-sulfonic acid, camphoric acid, meth-oxyacetic acid, tartaric acid, malic acid, diacetyltartaric acid, pyrrolidone-5-carboxylic acid and the like. The separated pure diastereomeric salts or esters can then be cleaved by conventional methods to obtain the individual optical isomers of the compounds of formula I or the alcoholic precursors. _ (j

A preferred subclass of compounds of the formula I are those of the formula:

ch-ch2-n

n

55

and their acid addition salts, in which R, R1 and p have the meanings given above.

Within the subclass defined above, those compounds are preferred in which R1 is halogen and R is alkyl, alkenyl, aralkenyl, halogen-substituted aralkenyl, aralkyl, halogen-substituted aralkyl, aryl or halogen-substituted aryl.

Of the compounds described in the preceding paragraph, those are particularly preferred in which [R1 ^ denotes one halogen atom or two halogen atoms and R represents alkyl having 1 to 12 carbon atoms, 2-alkenyl, phenyl-2-alkenyl, chlorine-substituted phenyl-2-alkenyl, benzyl, represents chlorine- or fluorine-substituted benzyl, phenyl or chlorine-substituted phenyl. Those compounds in which [R!] P denotes 2,4-dichloro, 2,4-dibromo or 2,4-difluoro are very particularly preferred.

The present compounds of formula I show anti-fungal (i.e. fungistatic or fungicidal) and antibacterial activity. E.g. show the compounds of formula I antifungal activity against human and animal pathogens, such as Microsporum audouini,

Microsporum gypseum,

Microsporum gypseum-canis,

Epidermophyton floccosum,

Trichophyton mentagrophytes,

Trichophyton rubrum,

Trichophyton tonsurans,

Candida albicans and Cryptococcus neoformans.

The compounds of the formula I also show antifungal activity against fungi of mainly agricultural importance, such as Aspergillus flavus,

Cladosporium herbarum,

Fusarium graminearum,

Pénicillium notatum,

Aspergillus niger,

Pénicillium oxalicum,

Pénicillium spinulosum and Pithomyces chartarum.

In addition, the compounds of the formula I have antibacterial activity against human and animal pathogens, such as Staphylococcus aureus,

Streptococcus faecalis,

Corynebacterium acnes,

Erysipelothrix insidiosa,

Escherichia coli,

Proteus vulgaris,

Salmonella choleraesuis,

Pasteurella multocida and Pseudomonas aeruginosa.

For pharmaceutical purposes, the compounds of formula I in the form of solid, semi-solid or liquid preparations, such as tablets, capsules, powders, suppositories, liquid

5,623,813

Compare solutions, suspensions, creams, lotions, ointments and deractive, non-ionic or cationic compounds. The compounds of formula I are used. As soil treatment against fungi or can be administered to humans and animals by conventional methods or the like, the present compounds can be administered as dusts, e.g. topically, orally, parenterally and the like in a mixture with sand, earth or a powdered clay. If the compounds are administered orally, alone or in a solid carrier, such as a mineral silicate, with or without a mixture with a suitable carrier, additional surface-active agents are applied, or dosages of approximately 12.5 to approximately 1000 mg per dose the present compounds can be applied in the form of an aqueous (assuming a human or animal of 70 kg of spray, which may or may not have a surface-active dispersing body weight) once or several times a day via a time average and a powdered solid carrier can be used from several days to many weeks. For the treatment of the leaves, the present. Suppositories can contain approx. 1 to 500 mg of active substance in the form of an aqueous compound on growing plants. sprays containing a surface-active dispersant

In view of the above effects, the or without a powdered solid carrier and hydro-

contains present compounds as useful antimicrobial agents, solvent applied.

proven not only for pharmaceutical but for industrial purposes, the present consumption can be for agricultural and industrial use. fertilize used to fight bacteria and fungi

The present invention thus further relates to being brought into contact with the means for inhibiting the growth of fungi or bacterial compounds in any known manner. Materials that bacteria can carry in plants or products in agriculture or fungi can be protected in industry; these compositions contain the present compounds by contacting them with the present compounds of the formula I in combination with a suitable carrier. brings, mixes or impregnates. To see the effect of the

For agricultural purposes, the compounds can increase the connections, they can be combined with other

of formula I directly on plants (e.g. seeds or leaves) or pesticides, such as fungicides, bactericides, insect

be applied to the ground. E.g. the vericides, miticides and the like can be combined. A compound of formula I can be applied to seeds alone or in a mixture with a particularly important industrial / agricultural application in a powdered solid carrier. Typical for the compounds of formula I is the use for powdered carriers are various mineral silicates, e.g. Preservation of food against bacteria and fun

Mica, talc, pyrophyllite and clays. The present gi, which is an impairment or spoilage of food

Compounds on seeds can also cause a mixture with a mittein.

conventional surfactants with or without 30 The present invention relates to methods of applying additional solid carriers. Any conventional anion-based reaction scheme can be used as the surface preparation of the new compounds of the formula I after the chemical active wetting agent:

(i-a)

à

_ 1

r

-

p chch2n

n so i

r

(i-b)

R

CHCH ^

LJ

so.

i

(i-c) •

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6

wherein R, R1 and p are as defined above and X is a conventional removable substituent such as chlorine, bromine or a reactive ester group, e.g. CH3-S02-0- or p-CH3-C6H4-S02-0-.

The l- [ß- (R-thio) phenylethyl] imidazoles of the formula IA 5 or their acid addition salts are prepared by condensing a compound of the formula II with a thiol of the formula III and optionally a free base of the formula I A is converted into one of its acid addition salts or an acid addition salt obtained is converted into the free base of the formula m IA.

In this condensation, the starting materials and reagents can be brought into contact with one another in any conventional manner and can be kept at a temperature sufficient for complete reaction for a sufficient time. Furthermore, the reaction products can be isolated from the reaction mixture and obtained, using conventional or per se known methods for carrying out such reactions as in the case of the reaction conditions. The type of substituent (X) that can be removed plays no decisive role; its selection is based on the relative reaction rates known for reactions of this type. Chlorine, bromine and the two ester groups given above are only typical examples.

In general, the reaction of compounds of formula II with compounds of formula III, wherein R is alkyl, alkenyl, aralkenyl, substituted aralkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aralkyl or substituted aralkyl, in the presence of an inert organic solvent, e.g. Tetrahydrofuran, ether, methanol and the like, and in 3 (1 presence of sodium hydride or other suitable base at a temperature of 20 to 66 ° C within a period of 30 minutes to 24 hours.

The reaction of compounds of formula II with compounds of formula III, wherein R is aryl or substituted aryl35, is usually carried out in the presence of an inert organic solvent, e.g. Acetone, methanol and the like, and in the presence of potassium carbonate or other suitable base under reflux for a period of 30 minutes to 12 hours.

To produce the l- [ß- (R-sulfinyl) phenylethyl] -bzw. l- [ß- (R-sulfonyl) phenylethyl] imidazoles of the formulas I — B or IC or their acid addition salts are prepared by condensing a compound of the formula II with a compound of the formula III to give an 1- [ß- (R- Thio) -phenylethyl] imidazole of the formula I-A or an acid addition salt thereof and oxidizes it, whereupon one optionally converts a free base of the formula IB or IC obtained into one of its acid addition salts or an acid addition salt obtained into the free base transferred to formula IB or IC. 50

The oxidation can be carried out by methods known to the person skilled in the art using hydrogen peroxide, an organic peracid such as peracetic acid, p-nitroperbenzoic acid or m-chloroperbenzoic acid, or an inorganic acid 55 such as periodic acid. The oxidation reaction is preferably carried out using m-chloroperbenzoic acid in a liquid reaction medium such as a chlorinated hydrocarbon.

In this oxidation, the starting materials and 60 reagents can be brought into contact in any expedient manner and can be kept at a temperature sufficient for complete reaction for a sufficient time. Furthermore, the reaction products can be isolated from the reaction mixture and recovered, and, as in the case of the reaction conditions,, even conventional or known processes for carrying out such reactions or analogous reactions can be used.

40

In general, when the compounds of formula I-A are contacted with at least about 1 equivalent of oxidizing agent, such as m-chloroperbenzoic acid, at a temperature of from about -30 to about + 30 ° C., preferably in an organic one Medium, such as chloroform, and for a period of about 30 minutes to about 6 hours, the corresponding sulfinyl products of formula IB. When the compounds of formula IA are contacted with at least about 2 equivalents of oxidizing agents, such as m-chloroperbenzoic acid, at a temperature of about 0 to about 60 ° C, preferably in an organic medium such as chloroform, and during a Period of about 1 to about 24 hours, the corresponding sulfonyl products of the formula IC are generally obtained.

The compounds of the formula I can be isolated in the form of the free bases; however, since many of the compounds in the form of the base are oils or gums, it is more expedient to isolate and characterize the compounds as acid addition salts. These salts can be prepared in a conventional manner, namely by reacting the base with a suitable inorganic or organic acid. If desired, the salts can easily be converted into the corresponding bases by treatment with alkali, such as potassium carbonate, sodium carbonate, sodium hydroxide or potassium hydroxide.

The starting compounds of formula II, wherein R1 is hydrogen, methyl, methoxy, halogen, nitro or lower alkylsulfonyl, are described in U.S. Patent No. 3,679,697, along with a process for their preparation. Compounds of formula II in which R1 is different from the groups mentioned in said patent, with the exception of groups R2SO-, can be prepared in an analogous manner, i.e. by bromination of the corresponding acetophenone, reaction of the resulting 2-bromoaceto-phenone with imidazole, reduction of the resulting 2- (l-imi-dazolyl) acetophenone with sodium tetrahydroborate and final reaction of the resulting 1-imidazoleethanol with a thionyl halide to give the l- (ß -Halogenphenyl-ethyl) -imidazole of the formula II. Compounds of the formula II, in which R1 denotes the group R2SO—, can be obtained by oxidation of the corresponding compounds of the formula II, in which R1 represents the group R2S-, using conventional methods known per se that have already been described.

If Acetophenone, which is a group of the formula:

-s (0) n

I.

R2

in which R2 has the meaning given above, as reactants for the preparation of starting compounds of the formula II, i.e. Compounds of the formula:

ch-ch.

so)

R

where R2 and X are as defined above, the acetophenones can be prepared by the following processes:

A) Friedel-Crafts acylation of a known alkyl, cycloalkyl, aralkyl or arylphenyl sulfide with acetyl chloride or acetic anhydride in the presence of aluminum chloride

7,623,813

to the corresponding alkylthio, cycloalkylthio, aralkyl 4-tert-butylthioacetophenone,

thio- or arylthioacetophenone, which by oxidation with was- 4-benzylthioacetophenone,

peroxide in acetic acid in the corresponding sulfonylde- 4- (4'-chlorobenzylthio) acetophenone,

can be transferred privately. These processes are described in Journal 4- (4'-methoxybenzylthio) acetophenone,

of the American Chemical Society 74,5475-5481 (1952) and 5 4-phenylthioacetophenone and in U.S. Patent 2,763,692. 4- (4'-chlorophenylthio) acetophenone,

B) Coupling a diazotized aminoacetophenone with replaced gives in a similar manner the following sulfonyl-an arylthiol or a substituted arylthiol, the substituted acetophenone:

substituted arylthiol at least one of halogen, Niederal- 4-tert-butylsulfonylacetophenone,

kyl, lower alkoxy, trifluoromethyl, nitro and cyano selected m 4-benzylsulfonylacetophenone,

Contains substituents to the substituted arylthioacetophe- 4- (4'-chlorobenzylsulfonyl) acetophenone,

non. However, a diazotized arylamino compound 4- (4'-methoxybenzylsulfonyl) acetophenone,

tion which is substituted by at least one of the above substituents 4-phenylsulfonylacetophenone and with a mercaptoacetophenone to give the substi- 4- (4'-chlorophenylsulfonyl) acetophenone.

couple arylthioacetophenone. These processes are in î s The starting compounds of formula II are derived from the

Boll. sci. fac. chim. ind. Bologna 17.33-43 (1959). above sulfonyl-substituted acetophenones according to the in

C) Alkylation of an o-, m- or p-mercaptoacetophenone US Pat. No. 3,679,697 described method prepared with a known alkyl, cycloalkyl, aralkyl or substituted.

tuated aralkyl halide, the substituted aralkyl halo

genid in the aryl radical by at least one from halogen, lower 2 »Example 1

alkyl, lower alkoxy, trifluoromethyl, nitro and cyano selected- A) A mixture of 1 g of l- (2,4, ß-trichlorophenylethyl) -

ten substituents is substituted to the corresponding Al imidazole, 1.8 g of 3,4-dichlorothiophenol and 1.5 g of potassium carbonyl, cycloalkyl, aralkyl or substituted aralkylthioacetate in 50 ml of acetone with stirring for 4 hours long to the tophenon. This procedure is refluxed in the Journal of the American. The solvent is mixed in a vacuum

Chemical Society 78,4792-4797 (1956). 25 evaporates, whereupon the residue is mixed with 20 ml of water.

By oxidation of the products of processes B) and C) in the resulting aqueous mixture is extracted with ether in the manner described in connection with process A) and the ether extract with 50 ml of a saturated sodium chloride, the corresponding R2-sulfonylacetophenones, in which R2 rid solution can be washed . The organic phase will be generated via Magne - which has the above meaning. dried and evaporated sodium sulfate and provides l- [2,4-di-

The following preparations and examples are used for 30 chloro-ß- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole. The oxalic acid salt of the free base is produced by the present invention. etheric oxalic acid is allowed to drip into the free base in ether until the precipitation is complete. The product is isolated by preparation A filtration and on a mixture of acetone and

A mixture of 1.52 g of 4-mercaptoacetophenone, 1.72 g of 35 ethyl acetate was recrystallized, where mal- [2,4-dichloro-β-4-methoxybenzyl chloride and 1.5 g of anhydrous potassium carbo- (3 ', 4' -dichlorophenylthio) -phenylethyl] -imidazole oxalate from the nat is obtained in 50 ml of acetone with stirring in a nitrogen atmosphere melting point 161.5 to 163.5 ° C.

sphere heated to reflux. After 4 hours the Lö- B) If instead of l- (2,4, ß-trichlorophenylethyl) -

solvent and the excess 4-methoxybenzyl chloride in imidazole other starting materials of formula II, e.g. Evaporated in vacuo, whereupon the residue was mixed with water 40 l- (β-chlorophenylethyl) imidazole,

becomes. The resulting aqueous mixture is mixed with ether extra- (β-chloro-4-ethylphenylethyl) imidazole,

and the ether extract is washed with water, over magne- 1 - (ß-chloro-4-tert-butylphenylethyl) imidazole,

dried sodium sulfate and evaporated to dryness. The re- (ß-chloro-4-ethoxyphenylethyl) imidazole,

the resulting residue is recrystallized from cyclohexane and 1 - (ß-chloro-4-n-butoxyphenyläthyI) imidazole,

gives 4- (4'-methoxybenzylthio) acetohpenone. 45 l- (β-chloro-4-tert-butoxyphenylethyl) imidazole,

4- (4, ß-dichlorophenylethyl) imidazole,

If the 4-methoxybenzyl chloride is replaced by other aral-l- (3,4, ß-trichlorophenylethyl) imidazole,

alkyl halides or substituted aralkyl halides based on l- (4-bromo-ß-chlorophenylethyl) imidazole,

Aryl radical at least one of halogen, lower alkyl, lower al- l- (2,4-dibromo-ß-chlorophenylethyl) imidazole,

koxy, trifluoromethyl, nitro and cyano selected substituents 50 i- (ß-chloro-4-fluorophenylethyl) imidazole,

wear, replaced, you get in a similar way the corresponding- 1- (ß-chloro-2,4-difluorophenylethyl) imidazole,

the substituted aralkylthioacetophenones. 1 - (ß-chloro-2-trifluoromethylphenylethyl) imidazole,

The starting compounds of formula II are derived from the 1- (β-chloro-4-trifluoromethylphenylethyl) imidazole substituted aralkylthioacetophenones according to the in the

U.S. Pat. No. 3,679,697 describes the process described - 55 l- (β-chloro-4-cyanophenylethyI) imidazole,

posed. 1- (β-chloro-4-nitrophenylethyI) imidazole and 1- (β-chloro-2-thiocyanatophenylethyl) imidazole,

Using preparation B, the following 1 - [ß-

A mixture of 2 g of 4-methylthioacetophenone, 5 g of vinegar- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole, which, where acid and approximately 3.8 g of 30% hydrogen peroxide is given 60, by treatment in conventional So heated with ent-to 85 to 95 ° C until an exothermic reaction initiated speaking acids is characterized as acid addition salts. When the reaction subsides, give 0.002 g of palladium:

on charcoal and filter the reaction mixture through diatomaceous earth- [ß- (3 ', 4'-dichlorophenylthio) phenyethyl] imidazole. The filtrate is cooled to precipitate the product- l- [4-ethyl-ß- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole, which is isolated by filtration and air dried 65 l- ( 4-tert.-butyl-ß- (3 ', 4'-dichlorophenylthio) phenylethyl] -imi- and 4-methylsulfonylacetophenone provides. Dazol, nitric acid salt: decomposes at 142.5 to 146.5 ° C,

If the 4-methylthioacetophenone is replaced by other l- [4-ethoxy-ß- (3 ', 4'-dichlorophenylthio) -phenylethyl] -imida-

Acetophenones, e.g. zol,

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l- [4-n-butoxy-ß- (3 ', 4'-dichlorophenyIthio) phenylethyI] -imi-dazol,

l- [4-tert-butoxy-β- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

l- [4-chloro-ß- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

l- [3,4-dichloro-β- (3 ', 4'-dichlorophenylthio) phenylethyl] imi-

dazol, nitric acid salt: decomposes at 133 to 137 ° C,

l- [4-bromo-ß- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

l- [2,4-dibromo-ß- (3 ', 4'-dichlorophenyIthio) -phenyIäthyl] -imi-

dazol, nitric acid salt: decomposes at 132.5 to 134.5 ° C,

l- [4-fluoro-ß- (3 ', 4'-dichlorophenylthio) phenylethyI] imidazole,

l- [2,4-DifIuor-ß- (3 ', 4'-dichlorophenylthio) -phenylethyI] -imi-

dazol, oxalic acid salt: decomposes at 172.5 to 175 ° C,

l- [2-trifluoromethyl-ß- (3 ', 4'-dichlorophenylthio) phenylethyl] -

imidazole,

l- [4-trifluoromethyl-β- (3 ', 4'-dichlorophenylthio) phenylethyI] imidazole,

l- [4-cyano-β- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

l- [4-nitro-ß- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole and l- [2-thiocyanato-ß- (3', 4'-dichlorophenylthio) phenylethyl] imidazole.

C) If other starting materials of formula III, e.g. 4-chlorothiophenol and 2,4-dichlorothiophenol, instead of 3,4-dichlorothiophenol and the starting compounds of formula II listed above, are obtained in the same way, the following l- [ß- (R-thio) phenylethyl] imidazoles, which, where indicated, are characterized by treatment in a conventional manner with appropriate acids as acid addition salts: l- [ß- (4'-chlorophenylthio) phenylethyl] imidazole, oxalic acid salt: decomposition at 147.5 to 149 ° C., l- [ß- (2 ', 4'-dichlorophenylthio) phenylethyl] imidazole, l- [4-ethyl-ß- (4'-chirophenylthio) phenyethyl] imidazole, l- [4-ethyl I-ß- (2 ', 4'-dichlorophenylthio) phenylethyl] imidazole, l- [4-tert-butyl-ß- (4'-chlorophenylthio) phenylethyl] imidazole, l- [4-tert-butyl-ß - (2 ', 4'-dichlorophenylthio) phenyethyl] -imi-dazol,

l- [4-ethoxy-ß- (4'-chlorophenylthio) phenylethyl] imidazole,

l- [4-ethoxy-ß- (2 ', 4'-dichlorophenylthio) phenyethyl] imida

zol,

l- [4-n-Butoxy-ß- (4'-chlorophenylthio) phenylethyI] imidazole, l- [4-n-butoxy-ß- (2', 4'-dichlorophenylthio) phenylethyl] -imidol ,

l- [4-tert-butoxy-β- (4'-chlorophenylthio) phenylethyl] imidazole,

l- [4-tert-butoxy-ß- (2 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

l- [4-chloro-ß- (4'-chlorophenylthio) phenylethyl] imidazole, oxalic acid salt: decomposes at 190 to 191 ° C,

l- [4-chloro-ß- (2 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

l- [2,4-dichloro-β- (4'-chlorophenylthio) phenylethyl] imidazole,

nitric salt: mp 169.5 to 170 ° C,

l- [2,4-dichloro-ß- (2 ', 4'-dichlorophenylthio) phenylethyl] imim

dazol, nitric acid salt: mp 150 to 151 ° C,

l- [3,4-dichloro-β- (4'-chlorophenylthio) phenylethyl] imidazole,

nitric salt: decomposes at 123 to 125.5 ° C,

l- [3,4-dichloro-ß- (2 ', 4'-dichlorophenylthio) phenylethyl] imi-

dazol, oxalic acid salt: decomposes at 169 to 171.5 ° C,

l- [4-bromo-ß- (4'-chlorophenylthio) phenylethyl] imidazole,

l- [4-bromo-ß- (2 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

l- [2,4-dibromo-ß- (4'-chlorophenylthio) phenylethyl] imidazole,

l- [2,4-dibromo-ß- (2 ', 4'-dichlorophenylthio) phenylethyI] -imi-

dazol,

l- [4-fluoro-ß- (4'-chlorophenylthio) phenyethyl] imidazole,

l- [4-fluoro-ß- (2 ', 4'-dichlorophenylthio) phenyethyl] imidazole,

l- [2,4-difluoro-β- (4'-chlorophenylthio) phenylethyl] imidazole,

l- [2,4-difluoro-ß- (2 ', 4'-dichlorophenylthio) phenylethyl] -imi-dazole,

l- [2-trifluoromethyl-ß- (4'-chlorophenylthio) phenylethyl] -imi-dazole,

l- [2-trifluoromethyl-β- (2 ', 4'-dichlorophenylthio) phenylethyI] imidazole,

l- [4-trifluoromethyl-ß- (4'-chlorophenylthio) phenylethyl] -imi-dazole,

l- [4-trifluoromethyl-β- (2 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

l- [4-cyano-β- (4'-chlorophenylthio) phenylethyl] imidazole,

l- [4-cyano-ß- (2 ', 4'-dichlorophenylthio) phenylethyl] imida-

zol,

l- [4-nitro-ß- (4'-chlorophenylthio) phenylethyl] imidazole and l- [4-nitro-β- (2 ', 4'-dichlorophenylthio) phenylethyl] imidazole.

Example 2

A) A solution of 1 g of l- (2,4, ß-trichlorophenylethyl) imidazole in 10 ml of tetrahydrofuran is added to a mixture of 1 g of 2,4-dichlorobenzyl mercaptan and 220 mg of a 56% sodium hydride dispersion in 40 ml of tetrahydrofuran. The mixture is stirred at room temperature for 12 hours, the solvent is evaporated in vacuo and the residue is mixed with

10 ml water. The resulting aqueous mixture is extracted with ether and the ether extract is washed with 50 ml of a saturated sodium chloride solution. The organic phase is dried over magnesium sulfate and evaporated to give l- [2,4-dichloro-β- (2 ', 4'-dichlorobenzylthio) phenylethyl] imidazole.

The nitric acid salt of the free base is prepared by dropping nitric acid into the free base in ether until the precipitation is complete. The product is isolated by filtration and recrystallized from ethyl acetate to give l- [2,4-dichloro-β- (2 ', 4'-dichlorobenzylthio) phenylethyI] -imi-dazole nitrate, which is obtained at 133.5 decomposes up to 134.5 ° C.

B) If other starting materials of formula II, i.e. using the compounds listed in paragraph B of Example 1, the following l- [ß- (2 ', 4'-dichlorobenzylthio) phenylethyl] imidazoles are similarly obtained which, where indicated, are treated by treatment in a conventional manner corresponding acids can be characterized as acid addition salts:

l- [ß- (2 ', 4'-dichlorobenzylthio) phenylethyl] imidazole, l- [4-ethyl-ß- (2', 4'-dichlorobenzylthio) phenylethyl] imidazole, l- [4-tert .-Butyl-ß- (2 ', 4'-dichlorobenzylthio) phenylethyl] -imi-dazol,

l- [4-ethoxy-ß- (2 ', 4'-dichlorobenzylthio) phenylethyl] imidazole,

l-4-n-butoxy-ß- (2 ', 4'-dichlorobenzylthio) phenylethyI] imidazole,

l- [4-tert-butoxy-ß- (2 ', 4'-dichlorobenzylthio) phenylethyI] imidazole,

l- [4-chloro-β- (2 ', 4'-dichlorobenzylthio) phenylethyl] imidazole, l- [3,4-dichloro-β- (2', 4'-dichlorobenzylthio) phenylethyl] imidazole, nitric acid salt: decomposes at 107 to 110 ° C, l- [4-bromo-ß- (2 ', 4'-dichlorobenzylthio) phenylethyl] imidazole, l- [2,4-dibromo-ß- (2', 4'-dichlorobenzylthio) phenylethyl] iimazole,

l- [4-fluoro-ß- (2 ', 4'-dichlorobenzylthio) phenylethyl] imidazole,

l- [2,4-difluoro-ß- (2 ', 4'-dichlorobenzylthio) phenylethyl] imi-

dazol,

l- [2-trifluoromethyl-β- (2 ', 4'-dichlorobenzylthio) phenylethyl] imidazole,

l- [4-trifluoromethyl-β- (2 ', 4'-dichlorobenzylthio) phenylethyI] imidazole,

l- [4-cyano-ß- (2 ', 4'-dichlorobenzylthio) phenylethyI] imidazole,

8th

5

10th

IS

20th

25th

30th

35

40

45

50

55

60

(> 5

9

l- [4-nitro-ß- (2 ', 4'-dichlorobenzylthio) phenylethyI] imidazole and l- [2-thiocyanato ß- (2', 4'-dichlorobenzylthio) phenyethyl] imidazole.

C) If other starting materials of formula III, 5 e.g. 4-Chlorobenzyl mercaptan, 3,4-dichlorobenzyl mercaptan or heptyl mercaptan, instead of 2,4-dichlorobenzyl mercapto and the starting materials of formula II listed in paragraph B of Example 1, the following l- [ß- (R -Thio) -phenyIäthyl] -imida- 10 zole, which, where indicated, are characterized by treatment in a conventional manner with appropriate acids as acid addition salts:

l- [ß- (4'-chlorobenzylthio) phenylethyl] imidazole,

l- [ß- (3 ', 4'-dichlorobenzylthio) phenylethyl] imidazole, 15

l- [ß- (n-heptylthio) phenyethyl] imidazole,

l- [4-ethyl-β- (4'-chlorobenzylthio) phenylethyl] imidazole,

l- [4-ethyl-β- (3 ', 4'-dichlorobenzylthio) phenylethyl] imidazole,

l- [4-ethyI-ß- (n-heptyIthio) phenylethyI] imidazole,

1- [4-tert-Butyl-β- (4'-chlorobenzylthio) phenylethyl] imidazole, 20

oxalic acid salt: decomposition 156 to 158.5 ° C,

l- [4-tert-butyl-ß- (3 ', 4'-dichlorobenzylthio) phenyethyI] imi

dazol,

l- [4-tert-butyl-ß- (n-heptylthio) phenylethyl] imidazole, l- [4-ethoxy-ß- (4'-chlorobenzylthio) phenylethyl] imidazole, 25 l- [4- Ethoxy-ß- (3 ', 4'-dichlorobenzylthio) phenylethyl] -imi-dazol,

l- [4-ethoxy-ß- (n-heptylthio) -phenylethyl] -imidazole, l- [4-n-butoxy-ß- (4'-chIorbenzylthio) -phenyIäthyI] -imidazoI, nitric acid salt: decomposes at 113 to 114 ° C, 30

l- [4-n-butoxy-ß- (3 ', 4'-dichIorbzyIthio) -phenyIäthyl] -imi-dazol,

l- [4-n-butoxy-ß- (n-heptylhtio) phenyethyl] imidazole, oxalic acid salt: decomposition at 124.5 to 130 ° C, l- [4-tert-butoxy-ß- (4 ' -chlorbenzyIthio) -phenylethyl] -imida- 35 zol,

1 - [4-tert-butoxy-ß- (3 ', 4'-dichlorobenzylthio) phenylethyl] imidazole,

l- [4-tert-butoxy-ß- (n-heptylthio) -phenylethyl] -imidazole, l- [4-chloro-ß- (4'-chlorobenzyl! thio) -phenylethyl] -imidazole, 40 oxalic acid salt: Decomposition at 148 to 149.5 ° C, nitric acid salt: mp. 103.5 to 105.5 ° C,

l- [4-chloro-ß- (3 ', 4'-dichlorobenzylthio) phenylethyl] imidazole, l- [4-chloro-β- (n-heptylthio) phenylethyl] imidazole, l- [2.4 -DichIor-ß- (4'-ChIorbenzylthio) -phenyIäthyl] -imidazoI, 45 nitric acid salt: decomposition at 130.5 to 132 ° C, l- [2,4-dichloro-ß- (3 ', 4'-dichlorobenzylthio ) -phthyläthyI] -imi-dazol, nitric acid salt: decomposes at 95 to 96.5 ° C, 1 - [2,4-dichloro-ß- (n-heptylthio) -phenylethyl] -imidazole, oxalic acid salt: mp 106 up to 109 ° C, 50 l- [3,4-dichloro-ß- (4'-chlorobenzylthio) phenylethyl] imidazole, oxalic acid salt: decomposition at 174 to 175 ° C,

l- [3,4-dichloro-ß- (3 ', 4'-dichlorobenzylthio) phenylethyl] -imi-azole, oxalic acid salt: decomposition at 176 to 177.5 ° C, 1 - [3,4-dichloro- β- (n-heptylthio) phenylethyl] imidazole, 55

l- [4-bromo-ß- (4'-chlorobenzylthio) phenylethyl] imidazole, l- [4-bromo-ß- (3 ', 4'-dichlorobenzylthio) -phenyIäthyI] imidazole, l- [4- Bromo-ß- (n-heptylthio) -phenyIäthyl] -imidazole, l- [2,4-dibromo-ß- (4'-chlorobenzylthio) -phenyIäthyl] -imidazole, nitric acid salt: decomposes at 126.5 to 128 ° C , 60th

1 - [2,4-dibromo-ß- (3 ', 4'-dichlorobenzylthio) phenylethyl] -imi-dazole,

l- [2,4-dibromo-ß- (n-heptylthio) -phenylethyl] -imidazole, 1 - [4-fluorine-ß- (4'-chlorobenzylthio) -phenylethyl] -imidazole, f, 5 l- [4 -Fluoro-ß- (3 ', 4'-dichlorobenzylthio) -phenylethyl] -imidazoI, l- [4-Fiuor-ß- (n-heptylthio) -phenylethyI] -imidazole, l- [2,4-difluoro-ß - (4'-chlorobenzylthio) phenylethyl] imidazole,

623 813

l- [2,4-difluoro-ß- (3 ', 4'-dichlorobenzylthio) -phenylethyI] -imi-dazole, oxalic acid salt: decomposition at 89.5 to 93.5 ° C, l- [2,4- Difluoro-ß- (n-heptyIthio) -phenylethyl] -imidazole, l- [2-trifluoromethyl-ß- (4'-chlorobenzylthio) -phenylIethyl] -imidazole,

l- [2-Trifluoromethyl-ß- (3 ', 4'-dichlorobenzylthio) phenylethyl] imidazole, nitric acid salt: decomposes at 134.5 to 137 ° C, l- [2-trifluoromethyl-ß- (n-heptylthio ) -phenylethyI] imidazole, l- [4-trifluoromethyl-ß- (4'-chlorobenzylthio) phenyIäthyI] -imi-dazole,

1- [4 ~ trifluoromethyl-ß- (3 ', 4'-dichlorobenzylthio) phenylethyl] imidazole,

l- [4-trifluoromethyl-ß- (n-heptylthio) -phenylethyl] -imidazole, l- [4-cyano-ß- (4'-chlorobenzylthio) -phenylethyl] -imidazole, l- [4-cyano-ß- (3 ', 4'-dichlorobenzylthio) -phenylethyI] -imida-zole,

l- [4-cyano-β- (n-heptylthio) phenylethyl] imidazole,

l- [4-nitro-ß- (4'-chlorobenzylthio) phenylethyl] imidazole,

l- [4-nitro-ß- (3 ', 4'-dichlorobenzylthio) phenylethyI] imidazole,

l- [4-nitro-ß- (n-heptyIthio) phenyethyl] imidazole,

1 - [2-thiocyanato-ß- (4 '-chlorobenzylthio) -phenylethyl] -imida-

zol,

l- [2-Thiocyanato-ß- (3 ', 4'-dichlorobenzylthio) phenylethyl] imidazole and l- [2-thiocyanato ß- (n-heptylthio) phenylethyl] imidazole. Example 3

If you follow the procedure described in paragraph A of Example 1 using l- (2,4, ß-trichlorophenyl-ethyl) imidazole and l- (3,4, ß-trichlorophenylethyl) imidazole as starting materials of formula II and Repeating 4-trifluoromethyl-thiophenol, 4-chloro-3-trifluoromethylthiophenol, 3,4,5-trichloro-thiophenol and pentachlorothiophenol as starting materials of formula III gives the following l- [ß- (R-thio) -phenylethyl) -imidzaoles , which, where indicated, are characterized by treatment in a conventional manner with appropriate acids as acid addition salts: l- [2,4-dichloro-ß- (4'-trifluoromethylphenyIthio) phenyethyl] imidazole, oxalic acid salt: decomposition at 178 to 178 , 5 ° C, l- [2,4-dichloro-ß- (4'-chloro-3'-trifluoromethylphenylthio) phenylethyl] imidazole, oxalic acid salt: decomposes at 186 to 187.5 ° C,

l- [2,4-dichloro-ß- (3 ', 4', 5'-trichlorophenylthio) phenylethyl] imidazole, nitric acid salt: decomposes at 178 to 185.5 ° C, l- [2,4-dichloro -ß- (pentachlorophenylthio) phenylethyl] imidazole, nitric acid salt: decomposition at 201 to 202.5 ° C, l- [3,4-dichloro-β- (4'-trifluoromethylphenylthio) phenylethyl] imidazole, oxalic acid salt: decomposition at 170 to 171 ° C, l- [3,4-dichloro-ß- (4'-chloro-3'-trifluoromethylphenyIthio) -phenylethylj-imidazole, oxalic acid salt: decomposition at 165 to 166 ° C ,

l- [3,4-dichloro-β- (3 ', 4', 5'-trichlorophenylthio) phenylethyl] imidazole and l- [3,4-dichloro-β-pentachlorophenylthio) phenylethyl] imidazole.

Example 4

If the procedure described in paragraph A of Example 2 is repeated, but instead of 2,4-dichlorobenzylmer-captan, other starting materials of the formula III, e.g. Ethyl mercaptan,

Pentyl mercaptan,

Octyl mercaptan,

Nonyl mercaptan,

Dodecyl mercaptan,

Octadecyl mercaptan,

3-pheny ipropyl mercaptan

623 813

Cyclopentylpropyl mercaptan,

Cyclohexyl mercaptan,

Cyclohexylmethyl mercaptan,

Cyclohexylethyl mercaptan,

Cycloheptylmethyl mercaptan,

Allyl mercaptan,

2-octenyl mercaptan,

3-phenyl-2-propenyl mercaptan, 3- (4-chlorophenyl) -2-propenyl mercaptan,

3-hexinyl mercaptan,

2-octynyl mercaptan,

Benzyl mercaptan,

4-methylbenzyl mercaptan,

4-tert-butylbenzyl mercaptan, 4-trifluoromethylbenzyl mercaptan, 4-methoxybenzyl mercaptan, 3,4,5-trimethoxybenzyl mercaptan, 4-n-butoxybenzyl mercaptan,

2,4,5-trichlorobenzyl mercaptan,

4-bromobenzyl mercaptan,

4-fluorobenzyl mercaptan,

4-nitrobenzyl mercaptan and 4-cyanobenzyl mercaptan,

used, the following l- [2,4-dichloro-β- (R-thio) -phenylethyl] -imidazoles are obtained, which, where indicated, are characterized by treatment in a conventional manner with appropriate acids as acid addition salts: l- [2 , 4-dichloro-ß- (ethylthio) phenylethyl] imidazole, l- [2,4-dichloro-ß- (n-pentylthio) phenylethyl] imidazole, oxalic acid salt: flows together at 99 ° C, l- [2,4-dichloro-β- (n-octylthio) phenylethyl] imidazole, oxalic acid salt: mp. 101.5 to 103.5 ° C,

l- [2,4-dichloro-ß- (n-nonylthio) phenylethyl] imidazole, oxalic acid salt: gelled at 82.5 ° C,

l- [2,4-dichloro-ß- (n-dodecy! thio) phenylethyl] imidazole, oxalic acid salt: mp 124.5 ° C,

l- [2,4-dichloro-ß- (octadecylthio) phenylethyl] imidazole, oxalic acid salt: gelled at 91.5 to 150 ° C, l- [2,4-dichloro-ß- (3-phenylpropylthio) - phenylethyl] imidazole, oxalic acid salt: mp. 87.5 to 90 ° C,

l- [2,4-dichloro-β- (cyclopentylpropylthio) phenylethyl] imidazole,

l- [2,4-dichloro-ß- (cyclohexylthio) phenylethyl] imidazole, nitric acid salt: mp. 114.5 to 117.5 ° C, l- [2,4-dichloro-ß- (cyclohexylmethylthio) - phenylethyl] imidazole, oxalic acid salt: decomposition at 122.5 to 140 ° C, l- [2,4-dichloro-ß- (cyclohexylethylthio) phenylethyl] imidazole, oxalic acid salt: decomposition at 104 to 108.5 ° C, l- [2,4-dichloro-β- (cycloheptylmethylthio) phenylethyl] imidazole,

1 - [2,4-dichloro-ß- (allylthio) phenylethyl] imidazole, oxalic acid salt: mp. 84.5 to 123 ° C,

l- [2,4-dichloro-β- (2-octenylthio) phenylethyl] imidazole, oxalic acid salt: mp 112.5 to 116.5 ° C,

l- [2,4-dichloro-ß- (3-phenyl-2-propenylthio) -phenylethyl] -imidazole, oxalic acid salt: decomposition at 151 to 160.5 ° C, l- [2,4-dichloro- ß- (4'-chlorophenyl) -2-propenylthio) -phenyl-ethylj-imidazole, nitric acid salt: decomposes at 123 to 126 ° C,

1 - [2,4-dichloro-β- (3-hexynylthio) phenylethyl] imidazole, oxalic acid salt: mp 90.5 to 95 ° C,

1 - [2,4-dichloro-ß- (2-octynylthio) phenylethyl] imidazole, oxalic acid salt: decomposition at 118 to 119.5 ° C, 1 - [2,4-dichloro-ß- (benzylthio) - phenylethyl] imidazole, nitric acid salt: mp. 110 to 112 ° C,

l- [2,4-dichloro-ß- (4'-methylbenzylthio) phenylethyl] imidazole, nitric acid salt: mp. 110.5 to 112 ° C, l- [2,4-dichloro-ß- ( 4'-tert-butylbenzylthio) phenylethyl] imi-

dazol, nitric acid salt: decomposition at 162.5 to 163 ° C, l- [2,4-dichloro-ß- (4'-trifluoromethylbenzylthio) phenylethyl] imidazole, nitric acid salt: decomposition at 112 to 114 ° C, l - [2,4-dichloro-ß- (4'-methoxybenzylthio) -phenylethyl] -imida-5 zole, nitric acid salt: decomposes at 118 to 119.5 ° C, l- [2,4-dichloro-ß- ( 3 ', 4', 5 '-trimethoxybenzylthio) -phenyI-ethylj-imidazole, oxalic acid salt: gelled at 147 ° C, l- [2,4-dichloro-ß- (4'-n-butoxybenzylthio) -phenyIäthyl] - imida-zol,

io l- [2,4-dichloro-ß- (2 ', 4', 5'-trichlorobenzylthio) phenylethyl] imidazole, nitric acid salt: decomposes at 172.5 to 173.5 ° C,

l- [2,4-dichloro-ß- (4'-bromobenzylthio) phenylethyl] imidazole, nitric acid salt: decomposition at 137 to 138 ° C, 15 l- [2,4-dichloro-ß- (4'- fluorobenzylthio) phenylethyl] imidazole, nitric acid salt: decomposes at 104.5 to 107.5 ° C, l- [2,4-dichloro-ß- (4'-nitrobenzylthio) phenyethyl] imidazole, nitric acid salt: decomposes at 129.5 to 132 ° C, and

1- [2,4-dichloro-ß- (4'-cyanobenzylthio) phenylethyl] imidazoI, 2o nitric acid salt: decomposes at 119.5 to 123 ° C.

Example 5

If you follow the procedure described in paragraph A of Example 1 using l- (4, ß-dichlorophenylethyl) -25 imidazole and l- (2,4, ß-trichlorophenylethyl) imidazole as starting materials of formula II and other starting materials Formula III, e.g.

Thiophenyl,

ß-thionaphthol,

30 4-methylthiophenol,

4-methoxythiophenol,

3-methoxythiophenol,

2-chlorothiophenol,

3-chlorothiophenol,

35 2,5-dichIorthiophenol,

4-bromothiophenol,

4-fluorothiophenol,

4-nitrothiophenol,

4-aminothiophenol,

40 4-acetamidothiophenol and 4-cyanothiophenol,

repeated instead of 3,4-dichlorothiophenol, the following l- [4-chloro-ß- (R-thio) -phenylethyl] -imidazole and l- [2,4-dichloro-ß- (R-thio) - phenylethyl] imidazoles, which, where indicated at-45, are characterized by treatment in a conventional manner with appropriate acids as acid addition salts:

l- [4-chloro-ß- (phenylthio) -phenylethyl-imidazole, oxalic acid salt: decomposition at 166 to 167 ° C, 5 ° l- [4-chloro-ß- (2-naphthylthio) -phenylethyl] -imidazole, oxalic acid salt: mp. 193.5 to 194 ° C, l- [4-chloro-ß- (4'-methylphenylthio) phenyethyl] imidazole, oxalic acid salt: decomposition at 199.5 to 200 ° C, 1 - [ 4-chloro-ß- (4'-methoxyphenylthio) phenylethyl] imidazole, 55 oxalic acid salt: decomposes at 177 to 178 ° C,

l- [4-chloro-ß- (3'-methoxyphenylthio) phenylethyl] imidazole, oxalic acid salt: mp. 164.5 to 165.5 ° C, l- [4-chloro-ß- (2'-chlorophenylthio ) -pheny! ethyl] -imidazole, oxalic acid salt: mp. 177 to 178 ° C,

60 l- [4-chloro-ß- (3 '-chlorophenylthio) phenylethyl] imidazole, oxalic acid salt: mp 169.5 to 171.5 ° C, l- [4-chloro-ß- (2', 5'-dichlorophenylthio) phenylethyl] imidazole, oxalic acid salt: mp. 181.5 to 183.5 ° C, l- [4-chloro-ß- (4'-bromophenylthio) phenylethyl] imidazole, 65 oxalic acid salt : Decomposes at 185 to 186.5 ° C,

l- [4-chloro-ß- (4'-fluorophenylthio) phenylethyl] imidazole, oxalic acid salt: mp. 182.5 to 183 ° C,

11

623 813

1- [4-chloro-β- (4'-nitrophenylthio) phenylethyl] imidazole,

oxalic acid salt: mp. 203 to 204.5 ° C,

l- [4-chloro-ß- (4'-aminophenylthio) phenylethyl] imidazole,

l- [4-chloro-ß- (4'-acetamidophenylthio) phenylethyl] imida

zol, oxalic acid salt: mp. 149.5 to 152 ° C, 5

l- [4-chloro-ß- (4'-cyanophenylthio) phenylethyl] imidazole,

l- [2,4-dichloro-ß- (phenylthio) phenylethyl] imidazole,

l- [2,4-dichloro-ß- (2-naphthylthio) phenyethyl] imidazole,

l- [2,4-dichloro-β- (4'-methylphenylthio) phenylethyl] imida

zol, 10

l- [2,4-dichloro-β- (4'-methoxyphenyIthio) phenylethyI] imida

zol,

l- [2,4-dichloro-β- (3'-methoxyphenylthio) phenylethyl] imidazole,

1 - [2,4-dichloro-ß- (2 '-chlorophenylthio) -phenylethyl] -imidazole, î s 1 - [2,4-dichloro-ß- (3'-chlorophenylthio) -phenylethyl-imidazoI, l- [ 2,4-dichloro-ß- (2 ', 5'-dichlorophenyIthio) phenylethyl] -imi-dazole,

l- [2,4-dichloro-ß- (4'-bromophenylthio) phenylethyl] imidazole, l- [2,4-dichloro-ß- (4'-fluorophenylthio) phenylethyl] imidazole, 20 l- [ 2,4-dichloro-β- (4'-nitrophenylthio) phenylethyl] imidazole, l- [2,4-dichloro-β- (4'-aminophenylthio) phenylethyl] imidazole,

l- [2,4-dichloro-ß- (4'-acetamidophenyIthio) phenyethyl] -imi-dazol and 25

l- [2,4-dichloro-β- (4'-cyanophenylthio) phenylethyl] imidazole.

Example 6

A solution of 400 mg of l- [4-chloro-β- (4'-aminophenylthio) phenylethyl] imidazole oxalate in 20 ml of tetrahydrofuran, 30 containing 1 ml of triethylamine, becomes 0.5 ml of hexanoyl chloride given. The mixture is stirred at room temperature for 30 minutes, the solvent is evaporated off in vacuo and aqueous potassium carbonate is added to the residue. The resulting aqueous mixture is extracted with dichloromethane and the organic phase is acidified with oxalic acid. The product which precipitates is filtered off and recrystallized from a mixture of acetone and ethyl acetate, l- [4-chloro-β- (4'-hexanoylaminophenylthio) phenylethyl] imidazole oxalate having a melting point of 98.5 to 102 ° C receives.

If you use other acid chlorides, e.g. Propionyl chloride, n-valeryl chloride, decanoyl chloride and the like, instead of hexanoyl chloride, the corresponding compounds are obtained in a similar manner:

l- [4-chloro-ß- (4'-propionylaminophenylthio) phenylethyl] - 45 imidazole oxalate,

l- [4-chloro-ß- (4'-valeroylaminophenylthio) phenylethyl] iimazole oxalate,

1- [4-chloro-ß- (4'-decanoylaminophenylthio) phenylethyl] imidazole oxalate etc. 50

Example 7

1 g of l- [4-chloro-β- (4'-chlorophenylthio) phenyethyl] imidazole nitrate is treated with aqueous potassium carbonate until a pH of approximately 11 is reached, whereupon the free base, namely l- [4-chloro-ß- (4'-chlorophenyIthio) phenylethyl] -imi-dazol, which precipitates, is extracted with dichloromethane. The extract is dried over magnesium sulfate and evaporated. A solution of 700 mg of 85% m-chloroperbenzoic acid in 50 ml of chloroform is slowly added to the resulting residue in 50 ml of chloroform 60 at 0 ° C. while stirring. When the addition is complete, stirring is continued at 0 ° C for approximately 3 hours. The reaction mixture is then washed with aqueous potassium carbonate solution and aqueous sodium chloride solution, dried over magnesium sulfate and evaporated. The residue is crystallized from benzene and gives l- [4-chloro-ß- (4'-chlorophenylsulfinyl) phenylethyl] imidazole

40

from melting point 139 to 140 ° C, which is further characterized as an oxalic acid salt from melting point 167 to 167.5 ° C.

If the above procedure is repeated with the l- [ß- (R-thio) -phenylethyl] -imidazole salts obtained in Examples 1 to 6, the corresponding l- [ß- (R-sulfinyl) -phenylethyl is obtained in a similar manner ] -imidazoles, which can be further characterized by converting them in the usual manner into the acid addition salts indicated, for example l- [2,4-dichloro-ß- (n-dodecylsulfinyl) phenyethyl] imidazole, oxalic acid salt: decomposes at 134 to 138 ° C, l- [4-chloro-ß- (4'-chlorobenzylsulfinyl) phenylethyl ] -imidazole, nitric acid salt: decomposes at 161.5 to 162 ° C etc.

Example 8

1 g of l- [4-chloro-ß- (4'-chlorophenylthio) phenylethyl] imidazole nitrate is treated with aqueous potassium carbonate until a pH of approximately 11 is reached, whereupon the free base, namely l - [4-Chloro-ß- (4'-chlorophenylthio) phenylethyl] -imi-dazol, which separates out, is extracted with dichloromethane. The extract is dried over magnesium sulfate and evaporated. A solution of 1.7 g of 85% m-chloroperbenzoic acid in 50 ml of chloroform is slowly added to the resulting residue in 50 ml of chloroform at room temperature with stirring. When the addition is complete, stirring is continued for approximately 24 hours at room temperature. The reaction mixture is then washed with aqueous potassium carbonate solution and aqueous sodium chloride solution, dried over magnesium sulfate and evaporated. The residue is crystallized from benzene and gives l- [4-chloro-β- (4'-chlorophenylsulfonyl) phenylethyl] imidazole with melting point 176 up to 178.5 ° C.

If the above process is repeated with the l- [ß- (R-thio) -phenylethyl] -imidazoles obtained in Examples 1 to 6 or their acid addition salts, the corresponding l- [ß- (R-sulfonyl) -phenylethyl is obtained ] -imidazoles, which can be further characterized by conversion in the usual manner into the acid addition salts indicated, for example

l- [2,4-dichloro-ß- (dodecylsulfonyl) phenylethyl] imidazole, oxalic acid salt: decomposition at 105.5 to 110 ° C, l- [4-chloro-ß- (4'-chlorobenzylsulfonyl) phenylethyl ] -imidazole, nitric salt: decomposes at 181 ° C etc.

Example 9

A solution of 2 g of 85% m-chloroperbenzoic acid in 100 ml of chloroform is converted into a solution of 2.53 g of l- (β-chloro-4-methylthiophenylethyl) imidazole in 150 with stirring at 0 ° C. in the course of one hour ml of chloroform added dropwise. After 6 hours, the resulting solution is washed with aqueous potassium carbonate solution and with water. The organic phase is separated and dried over magnesium sulfate. Evaporation of the solvent gives 1- (ß-chloro-4-methylsulfinylphenylethyl) imidazole.

If the l- (ß-chloro-4-methylthiophenylethyl) -imidazole is replaced by other l- (ß-chlorothiophenylethyl) imidazoles, e.g. 1- (β-chloro-4-tert-butylthiophenylethyl) imidazole, 1- (β-chloro-4-benzylthiophenylethyl) imidazole, 1- [ß-chloro-4- (4'-chlorobenzylthio) phenylethyl] - imidazole, l- [ß-chloro-4- (4'-methoxybenzylthio) phenylethyl] imidazole, l- (ß-chloro-4-phenylthiophenyl) imidazole and l- [ß-chloro-4- (4'-chlorophenylthio ) -phenylethyl] -imidazoI, is obtained in a similar manner: l- (ß-chloro-4-tert-butylsulfinylphenylethyl) -imidazole, l- (ß-chloro-4-benzylsulfinylphenylethyl) -imidazole, l- [ β-chloro-4- (4'-chlorobenzylsulfinyl) phenylethyl] imidazole,

l- [ß-ChIor-4- (4'-methoxybenzylsulifinyl) phenylethyl] imidazole,

623 813

1 - (ß-Chloro-4-phenylisulfinylphenylethyl) imidazole and l- [ß-chloro-4- (4'-chlorophenylsulfinyl) phenylethyl] imidazole.

Example 10

Following the procedure described in paragraph A of Example 1 using 3,4-dichlorothiophenol as the starting material of Formula III and other starting materials of Formula II, e.g. l- (ß-chloro-4-methylthiophenylethyl) imidazole, l- (ß-chloro-4-tert-butylthiophenyethyl) imidazole, l- (ß-chloro-4-benzylthiophenyethyl) imidazole, l- [ß- Chloro-4- (4'-chlorobenzylthio) phenylethyl] imidazole, l- [ß-chloro-4- (4'-methoxybenzylthio) phenylethyl] imidazole, l- (ß-chloro-4-phenylthiophenylethyl) imidazole , sl- [ß-chloro-4- (4'-chlorophenylthio) phenylethyl] imidazole, l- (ß-chloro-4-methylsulfinylphenylethyl) imidazole, l- (ß-chloro-4-tert-butylsulfinylphenylethyl) -imidazole, l- (ß-chloro-4-benzylsulfinylphenylethyl) -imidazoI, l- [ß-chloro-4- (4'-chlorobenzylsulfinyl) -phenylethyl] -imidazoI, l- [ß-chloro-4- (4 ' methoxybenzylsulfinyl) phenylethyl] imidazole,

l- (β-chloro-4-phenylsulfinylphenylethyl) imidazole,

l- [ß-chloro-4- (4'-chlorophenylsulfinyl) phenylethyl] imidazole,

l- (β-chloro-4-methylsulfonylphenylethyl) imidazole,

l- (ß-ChIor-4-tert-butyIsulfonylphenyläthyI) imidazole,

l- (β-chloro-4-benzylisulfonylphenylethyl) imidazole,

l- [ß-chloro-4- (4'-chlorobenzylsulfonyl) phenylethyl] imidazole,

l- [ß-ChIor-4- (4'-methoxybenzylsulfonyl) phenylethyl] imida

zol,

Repeat 1 - (ß-chloro-4-phenylsulfonylphenylethyl) imidazole and l- [ß-chloro-4- (4'-chlorophenylsulfonyl) phenylethyl] imidazole instead of l- (2,4, ß-trichlorophenylethyl) imidazole , the following l- [ß- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazoles are obtained:

l- [4-methylthio-ß- (3 ', 4'-dichlorophenylthio) phenyethyl] -imi-dazole,

l- [4-tert-butylthio-β- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

l- [4-benzylthio-ß- (3 ', 4'-dichlorophenylthio) phenylethyl] -imi-dazole,

1- [4- (4-chlorobenzylthio) -ß- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

1- [4- (4-methoxybenzylthio) -ß- (3 ', 4'-dichlorophenylthio) -phenylethyl] imidazole,

l- [4-phenylthio-ß- (3 ', 4'-dichlorophenylthio) phenylethyl] -imi-dazole,

1- [4- (4-chlorophenylthio) -ß- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

l- [4-methylsulfinyl-β- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

l- [4-tert-butylsulfinyI-ß- (3 ', 4'-dichlorophenylthio) phenylethyl) imidazole,

l- [4-BenzylsulfinyI-ß- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

1- [4- (4-chlorobenzylsulfinyl) -ß- (3 ', 4'-dichlorophenylthio) -phenylethylj-imidazole,

1- [4- (4-methoxybenzylsulfinyl) -ß- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

l- [4-phenylsulfinyl-β- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

1- [4- (4-chlorophenylsulfinyl) -ß- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

l- [4-methylsulfonyl-β- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

l- [4-tert-butylsulfonyl-β- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole,

l- [4-benzylsulfonyl-β- (3 ', 4'-dichlorophenylthio) phenyethyl] imidazole,

1- [4- (4-chlorobenzylsulfonyl) -ß- (3 ', 4'-dichlorophenylthio) phenylethylimidazole,

l- [4- (4-methoxybenzylsulfonyl) -ß- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole, 5 l- [4-phenylsulfonyl-ß- (3', 4'-dichlorophenylthio) phenylethyl] -imidazole and l- [4- (4-chlorophenylsulfonyl) -ß- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole.

Example 11

By following the procedure described in paragraph A of Example 2 using 4-chlorobenzyl mercaptan as the starting material of Formula III and other starting materials of Formula II, namely the compounds of Formula II listed in Example 10, instead of 1- (2 , 4, ß-tri-chlorophenylethyl) imidazole repeated, the following l- [ß- (4'-chlorobenzylthio) -phenylethyl] -imidazoles are obtained: l- [4-methylthio) -ß- (4'-chlorobenzylthio ) -phenylethyl] -imida-zol,

20 l- [4-tert-butylthio-ß- (4'-chlorobenzylthio) phenylethyl] -imi-dazole,

l- [4-Benzylthio-ß- (4'-chlorobenzylthio) -phenylethyl] -imidazole, l- [4- (4-chlorobenzylthio) -ß- (4'-chlorobenzylthio) -phenyl-ethyl] -imidazole, 25 l - [4- (4-methoxybenzylthio) -ß- (4'-chlorobenzylthio) phenyl-ethylj-imidazole,

l- [4-phenylthio-ß- (4'-chlorobenzylthio) phenylethyl] imidazole, l- [4- (4-chlorophenylthio) ß- (4'-chlorobenzylthio) phenylethyl] imidazole,

30 l- [4-methylsulfinyl-ß- (4'-chlorobenzylthio) phenylethyl] iimazole,

l- [4-tert-butylsulfinyl-β- (4'-chlorobenzylthio) phenylethyl] imidazole,

l- [4-benzylsulfinyI-ß- (4'-chlorobenzylthio) phenyethyl] -imi-35 dazol,

1- [4- (4-chlorobenzylsulfinyl) -ß- (4'-chlorobenzylthio) phenylethyl] imidazole,

l- [4- (4-Methoxybenzylsulfinyl) -ß- (4'-chlorobenzylthio) -phenylethyl] imidazole, 40 l- [4-phenylsulfinyl-ß- (4'-chlorobenzylthio) phenylethyl] -imidazole ,

1- [4- (4-qilorphenylsulfinyl) -ß- (4'-chlorobenzylthio) phenylethyl] imidazole,

l- [4-methylsulfonyl-β- (4'-chlorobenzylthio) phenylethyl] -imi-45 dazol,

l- [4-tert-butylsulfonyl-β- (4'-chlorobenzylthio) phenylethyl] imidazole,

l- [4-benzylsulfonyl-ß- (4'-chlorobenzylthio) pheny! ethyl] iimazole,

50 l- [4- (4-chlorobenzylsulfonyl) -ß- (4'-chlorobenzylthio) phenylethyl] imidazole,

1- [4- (4-methoxybenzylsulfonyl) -ß- (4'-chlorobenzylthio) -phenylethyl] imidazole,

l- [4-Phenylsulfonyl-ß- (4'-chlorobenzylthio) phenylethyl] -imi-55 dazol and l- [4- (4-chlorophenylsulfonyl) -ß- (4'-chlorobenzylthio) phenylethyl] imidazole .

Example 12

6 () If the procedure described in Example 7 is repeated using the corresponding amount of m-chloroperbenzoic acid with the products obtained in Examples 10 and 11, the following l- [ß- (R-sulfinyl) -phenylethyl-imidazoles are obtained : (, 5 l- [4-phenylthio-ß- (3 ', 4'-dichlorophenylsulfinyl) phenyI] ~ ethyl] imidazole,

1- [4- (4-chlorophenylthio) -ß- (3 ', 4'-dichlorophenylsulfinyl) -phenylethylj-imidazole,

13

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l- [4-methylsulfinyl-β- (3 ', 4'-dichlorophenyisulfinyl) phenylethyl] imidazole,

l- [4-tert-butylsulfinyl-ß- (3 ', 4'-dichlorophenylsulfylin) -phenylethyl] imidazole,

l- [4-BenzylsulfinyI-ß- (3 ', 4'-dichlorophenylsulfinyI) -phenyI- 5 ethyl] imidazole,

1- [4- (4-chlorobenzylsulfinyl) -ß- (3 ', 4'-dichlorophenylsulfinyl) phenylethylimidazole,

1- [4- (4-Methoxybenzylsulfinyl) -ß- (3 ', 4'-dichlorophenylisulfonyl) phenylethyl] imidazole, io l- [4-phenylsulfinyl-ß- (3', 4'-dich! orphenylsulfinyl ) -phenyl-ethyl] -imidazole,

1- [4- (4-chlorophenylsulfinyl) -ß- (3 ', 4'-dichlorophenylsulfinyl) phenylethyl-imidazole,

1- [4-methylsulfonyl-β- (3 ', 4'-dichlorophenylsulfinyl) phenyl-isethyl] imidazole,

l- [4-tert-butylsulfonyl-β- (3 ', 4'-dichlorophenylsulfinyl) -phenylethyl] imidazole,

1- [4-benzylsulfonyl-β- (3 ', 4'-dichlorophenylsulfinyl) phenylethyl] imidazole, 20

1- [4- (4-chlorobenzylsulonyl) -ß- (3 ', 4'-dichlorophenylsulfinyl) phenylethyl] imidazole,

1- [4- (4-methoxybenzylsulfonyl) -ß- (3 ', 4'-dichlorophenylsulfonyl) phenylethyl] imidazole,

1 - [4-phenylsulfonyl-β- (3 ', 4'-dichlorophenylsulfinyl) phenyl- 25 ethyl] imidazole,

1- [4- (4-chlorophenylsulfonyl-β- (3 ', 4'-dichlorophenylsulfinyl) phenylethyl-imidazole,

1 - [4-Phenylthio-β- (4'-chlorobenzylsulfinyl) phenylethyl] -imi-dazole, 30

1- [4- (4-chlorophenylthio) -ß- (4'-chlorobenzylsulfinyl) phenyl-ethyl-imidazole,

l- [4-methylsulfinyl-β- (4'-chlorobenzylsulfinyl) phenylethyl] imidazole,

l- [4-tert-butylsulfinyl-β- (4'-chlorobenzylsulfinyl) phenyl-35-ethyl] -imidazole,

1- [4 ~ benzylisulfinyl-ß- (4'-chlorobenzylsulfyl) phenylethyl] imidazole,

1- [4- (4-Chlorobenzylsulfinyl) -ß- (4'-chlorobenzylsulfinyl) phenylethyl] imidazole, 40

1- [4- (4-methoxybenzylsulfinyl) -ß- (4'-chlorobenzylsulfinyl) phenylethyl] imidazole,

l- [4-PhenyIsuIfinyI-ß- (4'-chlorobenzylsulfinyl) phenylethyl] imidazole,

1- [4- (4-chlorophenylsulfinyl) -ß- (4'-chlorobenzylsulfinyl) -phe- 45 nylethylj-imidazole,

1- [4-methylsulfonyl-β- (4'-chlorobenzylsulfinyl) phenylethyI] imidazole,

l- [4-tert-butylsulfonyl-β- (4'-chlorobenzylsulfinyl) phenylethyl] imidazole, so l- [4-benzylsulfonyl-β- (4'-chlorobenzylsulfinyl) phenylethyl] imidazole,

1- [4- (4-chlorobenzylsulfonyl) -ß- (4'-chlorobenzylsulfinyl) -phenylethylj-imidazole and l- [4- (4-methoxybenzylsulfinyl) -ß- (4'-chlorobenzylsulfinyl) - 55 phenylethyl] - imidazole,

Example 13

If the process described in Example 8 is repeated with the products obtained in Examples 10 and 11, M the following l- [ß- (R-sulfonyl) phenylethyl] imidazoles are obtained:

l- [4-phenylthio-β- (3 ', 4'-dichlorophenylsulfonyl) phenylethyl] imidazole,

l- [4- (4-chlorophenylthio) -ß- (3 ', 4'-dichlorophenylsulfonyl) - (, j phenylethyl] imidazole,

1- [4-phenylsulfinyl-β- (3 ', 4'-dichlorophenylsulfonyl) phenylethyl] imidazole,

1- [4- (4-chlorophenylsulfinyl) -ß- (3 ', 4'-dichlorophenylsulfonyl) phenylethyl] imidazole,

l- [4-methylsulfonyl-ß- (3 ', 4'-dichlorophenylsulfonyl) phenylethyl] imidazole,

l- [4-tert-butylsulfonyl-β- (3 ', 4'-dichlorophenylsulfonyl) -phenylethylj-imidazole,

l- [4-benzylsulfonyl-ß- (3 ', 4'-dichlorophenylisulfonyl) phenylethyl] imidazole,

1- [4- (4-chlorobenzylsulfonyl) -ß- (3 ', 4'-dichlorophenylsulfonyl) phenylethyl] imidazole,

1- [4- (4-methoxybenzylsulfonyl) -ß- (3 ', 4'-dichlorophenylsulfonyl) phenylethyl] imidazole,

l- [4-PhenyIsulfonyI-ß- (3 ', 4'-dichlorophenylsulfonyl) phenylethyl] imidazole,

1- [4- (4-chlorophenylsulfonyl) -ß- (3 ', 4'-dichlorophenylsulfonyl) phenylethyl] imidazole,

l- [4-phenylthio-ß- (4'-chlorobenzylsulfonyl) phenylethyl] iimazole,

1- [4- (4-chlorophenylthio) -ß- (4'-chlorobenzylsulfonyl) phenylethyl] imidazole,

l- [4-phenylsulfinyl-β- (4'-chlorobenzylsulfonyl) phenylethyl] imidazole,

1- [4- (4-chlorophenylsulfinyl) -ß- (4'-chlorobenzylsulfonyl) phenylethyl] imidazole,

l- [4-methylsulfonyl-β- (4'-chlorobenzylsulfonyl) phenylethyl] imidazole,

1- [4-tert-butylsulfonyl-β- (4'-chlorobenzylsulfonyl) phenylethyl] imidazole,

l- [4-benzylsulfonyl-β- (4'-chlorobenzylsulfonyl) phenylethyl] imidazole,

1- [4- (4 ~ chlorobenzylsulfonyl) -ß- (4'-chlorobenzylsulfonyl) -phenylethyl] imidazole,

1- [4- (4-methoxybenzylsulfonyl) -ß- (4'-chlorobenzylsulfonyl) phenylethyl] imidazole,

l- [4-PhenylsulfonyI-ß- (4'-chlorobenzylsulfonyl) phenylethyl] imidazole and l- [4- (4-chlorophenylsulfonyl) -ß- (4'-chlorobenzylsulfonyl) phenylethyl] imidazole.

Example 14

If the procedure described in Example 1 is repeated using the reactants required for the particular desired l- [ß- (R-thio) phenylethyl] imidazole, the following compounds are obtained, which, where indicated, by treatment in a conventional manner Characterized with appropriate acids as acid addition salts:

l- [2,4-dichloro-ß- (4'-nitro-3'-trifluoromethylphenylthio) phenylethyl] imidazole, nitric acid salt: decomposes at 127.5 to 130.5 ° C,

l- [4-trifluoromethyl-ß- (4'-tert-butylphenylthio) -phenyl-ethylj-imidazole, oxalic acid salt: mp 161 to 162 ° C, l- [2,4-dimethyl-ß- (3 ' , 4'-dichlorophenyIthio) phenylethyl] imidazole, nitric acid salt: decomposition at 165.5 to 166 ° C, l- [4-methoxy-ß- (3 ', 4'-dichlorophenylthio) phenylethyl] -imidol , oxalic acid salt: mp. 145.5 ° C, l- [4-methoxy-ß- (4'-tert-butylphenylthio) -phenylethyl] -imidazole, oxalic acid salt: mp. 139.5 to 141.5 ° C, l- [2,4-dimethoxy-ß- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole, nitric acid salt: decomposes at 155.5 to 158 ° C, l- [4-nitro-ß - (Pentachlorophenylthio) phenylethyl] imidazole, nitric acid salt: decomposes at 163.5 to 165.5 ° C, l- [2,4-dichloro-ß- (n-butoxyphenylthio) phenylethyI] imidazole, oxalic acid salt: Mp 143 to 144 ° C, l- [4-cyano-ß- (pentachlorophenylthio) phenylethyl] imidazole, nitric acid salt: mp 182.5 to 183.5 ° C (foaming), l- [4-n -Butylthio-ß- (4'-chlorophenylthio) -phenyIäthyI] -imida-zol and

{

623 813

14

1 - [4-Methylthio-β- (3 ', 4'-dichlorophenylthio) phenylethyl] -imi-dazole.

Example 15

If the procedure described in Example 2 is repeated using the reactants required for the particular desired l- [β- (R-thio) -phenylethyl-imidazole, the following compounds are obtained which, where indicated, are treated by conventional means can be characterized with appropriate acids as acid addition salts:

1 - [2,4-difluoro-ß- (n-nonylthio) phenylethyl] imidazole, oxalic acid salt: mp 79.5 to 84 ° C,

l- [2,4-Dimethyl-ß- (4'-chlorobenzylthio) phenylethyl] imidazole, oxalic acid salt: decomposes at 80.5 to 83 ° C, l- [4-methoxy-ß- (3- phenylpropylthio) phenylethyl] imidazole, oxalic acid salt: mp. 75 to 83 ° C,

1 - [4-methoxy-ß- (n-dodecylthio) phenylethyl] imidazole, oxalic acid salt: mp 90 to 93 ° C,

l- [2,4-dichloro-ß- (l'-naphthylmethylthio) -phenylethyl] -imi-dazole, oxalic acid salt: flows together at 86 ° C, foams at 86 to 121.5 ° C,

1 - [4-chloro-ß- (ethylthio) phenylethyl] imidazole, oxalic acid salt: mp. 157 to 158 ° C,

l- [2,4-dichloro-ß- (n-undec-10-enyIthio) phenylethyl] imidazole, oxalic acid salt: mp. 82 to 107 ° C, l- {2,4-dichloro-ß- [3- (4'-methylphenyl) prop-2-enylthio] phenylethyl} imidazole, nitric acid salt: mp. 133.5 to 137 ° C.,

l- {2,4-dichloro-β- [3- (4'-tert-butylphenyl) prop-2-enylthio] phenylethyl} imidazole, nitric acid salt: mp. 147 to 153.5 ° C,

l- [2,4-dichloro-β- (4-phenylbut-3-enylthio) phenylethyl] iimazole,

l- {2,4-dichloro-ß- [3- (4'-chlorophenyl) propylthio] phenylethyl} imidazole, oxalic acid salt: mp 111 to 113 ° C, l- [2,4-dichloro -ß- (prop-2-ynylthio) phenylethyl] imidazole, l- [4-methylthio-ß- (3 ', 4'-dichlorobenzylthio) phenylethyl] imiazole,

l- [4-n-butylthio-β- (4'-chlorobenzylthio) phenylethyl] imidazole,

l- [2,4-dichloro-ß- (n-hexylthio) phenylethyl] imidazole, l- [2,4-dibromo-ß- (n-hexylthio) phenylethyl] imidazole, l- [2,4 -Dibromo-ß- (n-octylthio) phenylethyl] imidazole, 1 - [2,4-difluoro-ß- (n-octylthio) phenylethyl] imidazole and l- [2,4-difluoro-ß- ( n-decylthio) phenylethyl] imidazole.

Example 16

1 g of l- [4-chloro-ß- (4'-chlorophenylthio) phenylethyl] imidazole nitrate is shaken in 100 ml of dichloromethane with excess dilute potassium carbonate solution until the salt is completely dissolved. The organic layer is then separated, washed with water and dried over magnesium sulfate. Evaporation of the solvent gives 1 - [4-chloro-ß- (4'-chlorophenylthio) phenylethyl] imidazole as a rubber.

Similarly, the acid addition salts of all compounds of formula I can be converted to the corresponding free bases, e.g.

l- [2,4-dichloro-ß- (3 ', 4'-dichlorophenylthio) phenylethyl] iimazole,

l- [2,4-dichloro-ß- (2 ', 4'-dichlorobenzylthio) phenylethyl] iimazole,

l- [2,4-dichloro-ß- (n-heptylthio) phenylethyl] imidazole, l- [2,4-dichloro-ß- (4'-chlorophenylthio) phenylethyl] imidazole, l- [2, 4-dichloro-ß- (4'-chlorobenzylthio) phenylethyl] imidazole etc.

Example 17

A solution of 2.5 g of l- [4-chloro-β- (4'-ch! Orphenylthio) phenylethyl] imidazole in 40 ml of anhydrous ether is added dropwise with 70% nitric acid (d = 1.42) while stirring ver-5 continues until precipitation is complete. The product is filtered off, washed with ether and dried. Recrystallization from ethyl acetate gives l- [4-chloro-ß- (4'-chlorophenylthio) phenylethyl] imidazole nitrate with a melting point of 136.5 to 137.5 ° C.

Similarly, all free bases of formula I can be converted into their acid addition salts by treatment in a conventional manner with corresponding acids.

Testing the antibacterial effect i5 The antibacterial effect of certain compounds of the formula I and of Keflin, i.e. the sodium salt of 7- (thio-phen-2-acetamido) cephalosporanic acid is explained in the following manner.

Streptococcus feacalis, a gram-positive bacterium, is grown 20 at 37 ° C in brain-heart infusion broth (Difco). After 24 hours, the culture is diluted with the growth medium to a concentration of 1X108 cells per ml. 0.05 ml each of this suspension are added to differently diluted solutions of the test compounds. 25 The test compounds are dissolved in a concentration of 10 mg per ml in dimethyl sulfoxide, ethanol or water and then diluted with sterile water to a stock solution with a concentration of 100 µg / ml. Suitable dilutions are made from this stock solution. Approximately 4 ml of each dilution is placed in a sterile test tube and 0.05 ml of the inoculum prepared above is added to each test tube. The test tubes are incubated for 24 hours, after which the minimum inhibitory concentration, i.e. the concentration at which no visible growth 35 occurs is determined.

Table I compound

Keflin l- [3,4-dichloro-ß- (3 ', 4'-dichlorophenylthio) phenylethyl] imidazole-45 nitrate l- [2,4-dichloro-ß- (4'-chlorobenzyl-

thio) -phenylethyl] -imidazole-

nitrate l- [4-chloro-ß- (4'-chlorophenylthio) -50 phenylethyl] imidazole nitrate

Minimum inhibitory concentration

(Hg / ml)

33

10th

10 3.3

Testing the antifugal effect

The antifungal (i.e. fungistatic or fungicidal) activity of certain compounds according to the invention and of 55 miconazoles, i.e. l- [2,4-dichloro-β- (2 ', 4'-dichlorobenzyloxy) phenylethyl] imidazole nitrate is explained in the following manner.

Trichophyton rubrum is grown on Sabourad dextrose agar (Difco) at room temperature for 14 days. The mushroom w) is then removed from the agar slant culture and homogenized in Sabourad dextrose broth to form a fine suspension. This suspension is diluted to a uniform concentration (optical density 0.1 at 600 nm); 0.05 ml each of the diluted suspension are added to various 65 dilutions of the test compounds.

The test compounds are dissolved in a concentration of 10 mg per ml in dimethyl sulfoxide, ethanol or water and then with sterile water to a concentration of

15

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Diluted 100 [Ag per ml. Suitable dilutions are made from this stock solution. Approximately 4 ml of each dilution is placed in a sterile test tube and 0.05 ml of the inoculum prepared above is added to each test tube. Depending on the growth in the negative comparison test, the incubation is carried out for 7 to 14 days.

Then for each test compound and for Miconazole the minimum inhibitory concentration, i.e. determines the concentration at which no visible growth occurs. The results obtained are summarized in Table II.

Tables connection

Miconazole (U.S. Patent No. 3,717,655) 1- [2,4-dichloro-β- (2 ', 4'-dichlorobenzylthio) phenylethyl] imidazole nitrate 1- [2,4-dichloro-β - (4'-chlorobenzyl-

thio) -phenylethyl] -imidazole-

nitrate l- [2,4-dich! or-ß- (n-heptylthio) phenylethyl] imidazole oxalate

Minimum inhibitory concentration (| xg / ml)

10th

3rd

3 3

C.

Claims (16)

623 813 1 - [2,4-dichloro-ß- (n-heptylthio) phenylethyI] imidazole and its acid addition salts, l- [2,4-dichloro-β- (n-octylthio) phenylethyl] imidazole and its acid addition salts, l- [2,4-dichloro-ß- (n-nonylthio) phenylethyl] imidazole and its acid addition salts, l- [2,4-dichloro-β- (n-hexylthio) phenylethyI] imidazoI and its acid addition salts, l- [2,4-dibromo-ß- (n-hexylthio) phenylethyl] imidazole and its acid addition salts, l- [2,4-dibromo-β- (n-heptylthio) phenylethyI] imidazole and its acid addition salts, l- [2,4-dibromo-ß- (n-octylthio) phenylethyl] imidazole and its acid addition salts, l- [2,4-difluoro-β- (n-octylthio) phenylethyI] imidazole and its acid addition salts, l- [2,4-difluoro-β- (n-nonylthio) phenyethyl] imidazole and its acid addition salts, l- [2,4-difluoro-ß- (n-decylthio) phenylethyl] imidazole and its acid addition salts, l- [2,4-dichloro-ß- (2-octenylthio) phenylethyl] imidazole and its acid addition salts, l- [2,4-dichloro-ß- (3-phenyl-2-propenyIthio) phenyethyl] -imi-azole and its acid addition salts, l- {2,4-dichloro-ß- [3- (4'-chlorophenyl ) -2-propenylthio] -phe-nylethyl} imidazole and its acid addition salts, l- [2,4-dichloro-ß- (4'-chlorobenzylthio) phenylethyl] imidazole and its acid addition salts, l- [2,4-dichloro-ß- (4'-fluorobenzylthio) phenylethyl] imidazole and its acid addition salts, l- [2,4-dichloro-ß- (2 ', 4'-dichlorobenzylthio) phenylethyl] -imi-dazole and its acid addition salts, l- [2,4-dichloro-ß- (3', 4'-dichlorobenzylthio ) -phenylethyl] -imidazole and its acid addition salts, l- [2,4-dibromo-ß- (4'-chlorobenzylthio) phenylethyl] imidazole and its acid addition salts, l- [2,4-dichloro-ß- (4'-chlorophenylthio) phenylethyl] imidazole and its acid addition salts, l- [2,4-dichloro-ß- (3 ', 4'-dichlorophenylthio) phenylethyl] -imidazole and its acid addition salts, l- [2,4-dichloro-ß- (2', 4'-dichlorophenylthio ) -phenylethyl] -imidazole and its acid addition salts, l- [2,4-dichloro-ß- (3 ', 4', 5'-trichlorophenylthio) phenylethyI] imidazole and its acid addition salts or l- [2, 4-dibromo-ß- (3 ', 4'-dichlorophenyIthio) phenylethyl] -imi-dazole and its acid addition salts. 2. The method according to claim 1, characterized in that R1 represents halogen and R represents alkyl, alkenyl, aralkenyl, halogen-substituted aralkenyl, aralkyl, halogen-substituted aralkyl, aryl or halogen-substituted aryl. 2nd PATENT CLAIMS 1. Process for the preparation of new compounds of the formula: ch-ch.-n Ï (I-A) and their acid addition salts, in which R denotes alkyl, alkenyl, aral-kenyl, substituted aralkenyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, aralkyl, substituted aralkyl, aryl or substituted aryl, where the substituted aralkenyl or the substituted aralkyl on the aryl radical comprises at least one Halogen, lower alkyl, lower alkoxy, trifluoromethyl, nitro and cyano bear substituents and the substituted aryl carries at least one substituent selected from halogen, lower alkyl, lower alkoxy, trifluoromethyl, nitro, amino, acylamino and cyano, furthermore R1 represents hydrogen, halogen, lower alkyl, lower alkoxy, Trifluoromethyl, nitro, cyano, thiocyanato or a group of the formula: -s (0) n I R2 R 2 represents alkyl, cycloalkyl, aralkyl, substituted aralkyl, aryl or substituted aryl, the substituted aralkyl or the substituted aryl on the aryl radical carrying at least one substituent selected from halogen, lower alkyl, lower alkoxy, trifluoromethyl, nitro and cyano, and wherein n and p are identical or different and represent 0, 1 or 2, characterized in that a compound of the formula: 25th 30th 35 40 (ii) wherein R1 and p have the meanings given above and X represents a removable group, with a compound of the formula: RSH (DI) 50 wherein R has the above meaning, condensed and optionally converting a free base of formula I-A obtained into one of its acid addition salts or converting an acid addition salt obtained into the free base of formula I-A. 3. The method according to claim 2, characterized in that [R '] p represents 1 or 2 halogen atoms and R alkyl having 1 to 12 carbon atoms, 2-alkenyl, phenyl-2-alkenyl, chlorine-substituted phenyl-2-alkenyl, benzyl, represents chlorine- or fluorine-substituted benzyl, phenyl or chlorine-substituted phenyl. 4. The method according to claim 2 or 3, characterized in that [R '] p means 2,4-dichloro, 2,4-dibromo or 2,4-difluoro. 5. The method according to claim 4 for the preparation of l- [2,4- Dichloro-β- (n-pentylthio) phenylethyI] imidazole and its acid addition salts, 6. The method according to claim 1, characterized in that a compound obtained, in which R is aminophenyl, is acylated with an acid chloride to the corresponding compound in which R is acylaminophenyl. 7. Process for the preparation of new compounds of the formula: 55 ch-ch0n I l s (0) (I — B or I-C) and their acid addition salts, in which R, R1 and p have the meanings given in claim 1 and q is 1 or 2, where the value of q can only be greater than the value of n if R2 is aryl or substituted aryl, characterized in that a compound of the formula IA or an acid addition salt thereof is prepared by the process according to claim 1 and this (s) is oxidized, whereupon optionally a free base of the formula IB or IC obtained is converted into one of its acid addition salts or an acid addition salt obtained is in the free base of formula IB or IC transferred. 8. The method according to claim 7, characterized in that R1 represents halogen and R represents alkyl, alkenyl, aralkenyl, halogen-substituted aralkenyl, aralkyl, halogen-substituted aralkyl, aryl or halogen-substituted aryl. 9. The method according to claim 8, characterized in that [R '] p represents 1 or 2 halogen atoms and R alkyl having 1 to 12 carbon atoms, 2-alkenyl, phenyl-2-alkenyl, chlorine-substituted phenyl-2-alkenyl, benzyl, represents chlorine- or fluorine-substituted benzyl, phenyl or chlorine-substituted phenyl. 10. The method according to claim 8 or 9, characterized in that [R '] p means 2,4-dichloro, 2,4-dibromo or 2,4-difluoro. 11. Agent for the inhibition of the growth of fungi or bacteria in plants or products in agriculture or industry, characterized in that it is a new compound of the formula IA, IB or IC or an acid addition salt thereof as an active ingredient mixed with a carrier. 12. Composition according to claim 11, characterized in that the active ingredient is present in an amount in the range between 0.1 and 10.0% by weight, based on the composition. 13. Composition according to claim 11 or 12, characterized in that q = 0. 14. Composition according to one of claims 11 to 13, characterized in that R1 represents halogen and R represents alkyl, alkenyl, aralkenyl, halogen-substituted aralkenyl, aralkyl, halogen-substituted aralkyl, aryl or halogen-substituted aryl. 15. Composition according to claim 14, characterized in that [R '] p represents 1 or 2 halogen atoms and R alkyl having 1 to 12 carbon atoms, 2-alkenyl, phenyl-2-alkenyl, chlorine-substituted phenyl-2-alkenyl, benzyl, represents chlorine- or fluorine-substituted benzyl, phenyl or chlorine-substituted phenyl. 16. Composition according to subclaim 14 or 15, characterized in that [R!] P denotes 2,4-dichloro, 2,4-dibromo or 2,4-difluoro.