NO823978L - PROCEDURE FOR THE PREPARATION OF IMIDAZOLS. - Google Patents

Description

The object of the invention is a new method for the preparation of imidazoles with formula

in which R^ as well as at least one of the residues and R^ means an organic residue bonded over a carbon atom, and a different residue Rp or R^ means hydrogen, as non-aromatic residues Rg bonded over saturated carbon atoms and can also be connected with each other, with the precaution that R^ is different from residues of formula -A-O-R., -A-S(O) -R. and -A-Rc»4 n 4j in which A means a divalent hydrocarbon residue, R4, an optionally substituted hydrocarbon residue, n means 0, 1 or 2, and R^ means optionally esterified or amidated carboxy, when R^ and R^

means aromatic residues,

as well as their salts.

Imidazoles of formula I have diverse industrial application possibilities. Thus, the compound of formula I is referred to in which at least two of the residues R^, R^ and R^ independently mean furyl, thienyl, pyridyl, phenyl, lower alkylphenyl, lower alkoxyphenyl, lower alkylthiophenyl, halophenyl, trifluoromethylphenyl, 3,4-dimethoxyphenyl or 2,4 -dichlorophenyl, and a different party therefrom means trifluoromethyl or alkyl,

and their salts, in US Patent No. 3, 707,475 as anti-inflammatory, further it is for J. Chem. Soc. 278 (1941) known that 2-substituted 4,5-diphenylimidazoles, whose 2-substituent is aryl or alkyl, have chemiluminescent properties, and from US patent 1.1 06,599, of 2, 4." 5-triarylimidazoles have phototropic, electro-photographic and xerographic application possibilities.

Furthermore, imidazoles of formula I, in which R 2 means lower alkyl, cycloalkyl or optionally with lower alkyl, lower alkoxy or halogen substituted phenyl and one of the residues. R£ and R^ optionally means with lower alkyl, lower alkoxy, lower alkylthio, lower alkanesulfonyl, hydroxy or halogen substituted phenyl and the other means an optional N-oxidized 6-membered heteroaromatic residue with 1 or 2 nitrogen atoms according to US Patent No. 3" 929-807 anti-inflammatory properties.

The invention consequently also relates to the use of the new process for the preparation of known imidazoles of formula I, for example those in which at least two of the radicals Ry R^ and R^ independently of each other mean furyl, thienyl, pyridyl, phenyl, lower alkylphenyl, lower alkoxyphenyl, lower alkylthiophenyl, halophenyl , trifluoromethylphenyl, 3»4-dimethoxyphenyl resp. 2,4-dichlorophenyl and a residue different from this means trifluoromethyl or alkyl or in which R^ means lower alkyl, cycloalkyl or optionally with lower alkyl, lower alkoxy or halogen substituted phenyl and one of the residues R£ and R^ means optionally with lower alkyl, lower alkoxy , lower alkylthio, lower alkanesulfonyl, hydroxy or halogen substituted phenyl and the other means an optionally N-oxidized 6-membered heteroaromatic residue with 1 or 2 nitrogen atoms.

It is true that some methods are already known for the preparation of imidazoles of formula I, which, however, all have fundamental disadvantages, which limit their possibilities of application, resp. stand in the way of their transfer to an industrial scale.

Thus, imidazoles of formula I are usually prepared by reacting a diketone of formula R^-Gi^)-^.^ (II)

with ammonia or an ammonia-releasing agent and an alde-

hyd of formula R^-CHO (III). This method, which is for example described in detail in Swiss patent 561,202, has the disadvantage that starting substances with formulas II and III are used in a favorable oxidation step. Thus, diketones of formula III must usually first of all be prepared by a preceding oxidation

step during formation of .1,2-dioxoethylene group from 1- or 2-oxoethylene group, 1-hydroxy-2-oxo resp. 2-hydroxy-1-oxoethylene group or vinyl group from more readily available primary products. Thus, diketones of formula III are obtained according to the Swiss patent no. 5^1,202, for example by oxidation of corresponding monoketones of formula R2-CHg-C(=0)-R^ (IV) resp.

styryl compounds with the formula R2-CH=CH-R^(V) using selenium dioxide or by oxidation of corresponding hydroxy ketones with the formula R2-CH(OH )-C(=0 }-R^ (VI) using copper-II salt is. The high toxicity of the selenium dioxide used in the first instance and the reaction products formed is a major safety and environmental risk which, if possible, can only be kept within sustainable limits with a lot of work. in another case, reaction products with formula I are obtained in the form of copper II complexes. These must be released by the desired imidazoles. For this, the reaction is carried out with physiologically dangerous hydrogen sulphide. A further disadvantage is that copper sulphide is formed as an additional reaction product, which considerably pollutes the environment, either must be neutralized, stored for the time being or reprocessed, likewise the aldehydes with formula IV are only - rarely - available in larger quantities.

They must usually first be formed starting from the corresponding carboxylic acids or carboxylic acid halides by reduction.

In a variant of the above method is indicated

in Swiss patent no. 561,202 that one can α-oximate the compounds of formula V, primarily by means of nitric acid, and can use the formed oxime of formula R2~C(=N0H)-C(=0)-R3 (VIII). Thereby, however, 1-N-oxides are obtained

of the compounds of formula I, of which these must be released by subsequent reduction.

Furthermore, it is known and discussed for example in Swiss patent 561,716 to react N-acylated α-amino ketones with the formula R2-CH(NHCOR1)-C(=0)-R2(VIII) with ammonia or ammonia-releasing agents. This method has the disadvantage that the amino ketones can only be obtained by several, on a technical scale, cumbersome syn t es et rin. For example, the amino ketones are obtained by transferring corresponding hydroxy ketones to oximes and then reducing these with hydrogen to amino ketones, which are also known to be not very stable. The N-acylation finally takes place by reaction with reactive acid derivatives which again must first be prepared from carboxylic acids.

If a further procedure is mentioned, e.g.

in Swiss patent 561,717, a reactive pre-esterified α-hydroxyketone with the formula R^-CH(X ) - C(=0 ) -R^ (IX) is condensed,

wherein X means reactive esterified hydroxy, e.g. halogen, especially chlorine or bromine, with an amidine of formula R.| -C ( =NH )-NHg (XII). This avoids the above-mentioned detour over aminoketones, however, the production of the amidines, which are also only stable and can be used in salt form, also requires a multi-step process, usually starting from ecologically unfavorable nitriles, which in turn have to be prepared from other carboxylic acid derivatives. In a modification of this method, according to Chem Ber. 86, 88-93 convert hydroxy- resp. halogen ketones with formamide, and thus arrive at unsubstituted imidazoles. However, as expressly stated in the above quote, the process cannot be transferred to other carboxylic acid amides, and is thus in principle not considered as a production process for the two substituted imidazoles of formula I.

A further seen possibility for imidazoles of formula I can be derived from Swiss patent no. 561,718, in which preparation from oxazoles and ammonia and/or formamide is mentioned. Unlucky here is also the extra necessary multi-step synthesis route for the production of oxazole intermediates.

Thus, for example, hydroxy ketones of formula VII are converted with reactive derivatives of carboxylic acids of formula R^-C00H (X) into the corresponding esters, these are then treated with an ammonia-releasing agent, and thus obtain-

the oxazoles used according to the method.

The invention was therefore based on that task

to provide a process for the production of imidazole compound see with formula I, which is distinguished by a minimum of environmental impact by using inexpensive starting material in a small number of process steps, and by easy-to-handle process management. The task is solved according to the invention by reacting a reactive esterified hydroxyketone with the formula R2-CH(X)-C(=0)-R^(ix), where X means a reactive

efficiently esterified hydroxy group or a salt thereof, with an ammonium salt of formula

R1-C00 9 NH<9>(X)

if necessary in the presence of ammonia or an ammonia releasing agent.

As an ammonia-releasing agent, it comes through

next to an excess of the salt of formula X, for example in consideration ammonium salt is of a weaker acid compared to the acid of formula -C00H (XI), such as ammonium carbonate,

respectively -carbamate.

The invention therefore relates in the same way to the process variants according to which a compound of formula IX is reacted with the smallest double molar amount of an ammonium salt of formula X, or a compound of formula IX with the approximately equimolar amount of an ammonium salt of formula X, and the least equimolar amount, preferably between about 3 to 5 times the molar amount of ammonia, or an ammonia-releasing agent.

A reactive esterified hydroxy group is, for example, a hydroxy group esterified with strong inorganic or organic acids, such as strong mineral acids, e.g. halohydrogen acids, such as hydrochloric or hydrobromic acid, or strong organic sulphonic acids, such as corresponding lower alkane or aryl sulphonic acids, e.g. methane- or an optionally substituted benzene-sulfonic acid, and means e.g. halogen such as chlorine or bromo»lower alkylsulfonyloxy, e.g. methyl or ethylsulfonyloxy, or arylsulfonyloxy, e.g. p-toluene or benzenesulfonyloxy.

The ammonium salt of formula X can also be formed in situ under the reaction conditions, for example by having the acid of formula XI in the reaction mixture and mixing with liquid or gaseous ammonia. In this embodiment, ammonia can also be added in the form of a salt with a

to the acid of formula XI weaker acids, as a salt of carbonic acid, eg as ammonium carbonate or carbamate.

The reaction is carried out in the presence or absence of

a solvent that is inert under the reaction conditions at an elevated temperature, for example . at 60 to 180°C, preferably in the temperature range from 90 to 120°C.

Suitable solvents include e.g.

in terms of optionally halogenated hydrocarbons such as optionally halogenated aliphatic, cycloaliphatic or aromatic hydrocarbons, such as hexane, cyclohexane, toluene, chloroform or chlorobenzene, alkanols such as propanol, isopropanol, butanol, pentanol or octanols, ethers* such as dimethoxyethane, ethylene glycol mono-ethyl ether , dioxane or tetrahydrofuran, lower alkane carboxylic acids such as formic or acetic acid or preferably acids of formula XI, amides such as lower alkane carboxylic acid amides, e.g. formamides or dimethylformamide, or lactams, e.g. N-methylpyrrolidone, sulfoxides, such as dimethyl sulfoxide or water. A preferred embodiment of the preparation according to the invention of the compound of formula I consists in reacting a compound of formula IX, in which X for example means halogen, such as bromine, at a reaction temperature of approx. 100°C with an ammonium salt of formula X. The compound of formula X is thereby added in excess, e.g. in a ratio in relation to esters of formula IX from approx. 4.:1 to approx. 6:1, can be formed in situ, as e.g. reacts the corresponding acid under the reaction conditions i. with liquid ammonia. In a further preferred embodiment of the method according to the invention, the acid of formula XI can be added in excess, as well as serving as a solvent for the reaction. ;The starting substances of formula IX are only partially known. They can be used, for example, by ester condensation of an esterified acid of the formula R^-CHg-COOH with an esterified acid of the formula R^-COOH, preferably in the presence of a base. The resulting armed ylene ketone of formula R2-CH2-C(=0)-R^ (IV) is brominated, for example, and thus transferred into a compound of formula IX, in which X means bromine. The method according to the invention is distinguished in relation to the known methods mentioned in that, when starting from readily available starting materials, several processing steps are saved, and that no, or only to a small extent, ecologically harmful waste substances. Thus, by overcoming a prejudice existing among professionals (Chem. Ber. cited above), that the reaction of α-halo ketones with higher acid amides did not lead to imidazole compounds, a surprisingly successful way to arrive at a simple inexpensive ecologically harmless and an easily transferable process on a technical scale for the preparation of imidazoles of formula I from correspondingly reactive esterified α-hydroxy ketones and ammonium salts of corresponding organic carboxylic acids. The invention relates above all to a process for the preparation of imidazole derivatives of the general formula I, in which R^ means a branched lower alkyl radical with up to and including 4 C atoms, or one optionally substituted with a halogen with up to and including atomic number 35 such as chlorine phenyl radical, and at least one of the radicals R^ and R^ means one with halogen up to and including atomic number 35 lower alkyl up to and including 4 C atoms, lower alkoxy up to and including 4 C atoms or lower alkylthio with up to and including 4 C atoms, which methylthio, p-substituted with lower alkoxy with up to and including 4 C atoms, such as methoxy, m- and p-substituted or with halogen; with atomic number up to and including 35 as chlorine o- and p-substituted phenyl residue, and a residue different therefrom R2 or R^ means pyridine or 1-oxido-pyridyl as 3-pyridyl, furyl, as 2-furyl or thienyl as 2-thienyl, as well as their salts. The invention relates in particular to the methods listed in the examples. The invention also relates to the embodiments of the method according to which one starts from a compound obtained at one or another step of the method, and carries out the missing method step or interrupts the method at one or another step, or where one optionally forms in situ a starting material under the reaction conditions. ;Example 1; 3.57 g of a-bromo-benzyl-3-pyridyl-ketone hydrobromide are stirred with 5.95 g of ammonium pivalate in 50 g of pivalic acid for 5 hours at 100 C. After cooling, the reaction solution is mixed with 50 ml of ethyl acetate and made alkaline with 80 ml 2 5% ammonia. The organic phase is separated and the water phase is extracted again with ethyl acetate. One is .washing with water and drying over sodium sulphate is distilled off and the solvent. The residue is dissolved hot in acetonitrile, and brought to crystallization on cooling. After filtration and subsequent re-dissolution from acetonitrile, 2-tert.-butyl-4(5)-phenyl-5(4)-(3-pyridyl)-imidazole is obtained, m.p. 191-192°C. The starting material can be prepared as follows: To a solution of 66.0 g of nicotinic acid methyl ester, add 35.4 g of sodium methylate to 52 ml of toluene. It is heated to boiling, and then a solution of 80.1 g of phenylacetic acid emethyl ester in 270 ml of toluene is slowly added dropwise over the course of 2 1/2 hours. At the same time, 130 ml of a mixture of methanol and toluene are distilled off on a descending cooler. Distillation is then continued slowly until the reaction mixture reaches a temperature of 108°C. It is cooled to room temperature, and the mixture is allowed to flow while cooling to a mixture of 150 ml conc. hydrochloric acid and 130 ml of water. It is further heated to boiling for 5 hours, then cooled to 10°C and the precipitated product is filtered off. It is washed with 2 x 50 ml of toluene and dried in vacuum at 60°C. Benzyl-3-pyridyl ketone hydrochloride is obtained, m.p. 219-221°C, yield 99.3 g (86% of theory). Example 2: 16.5 g of a-bromo-benzyl-3-pyridyl-ketone hydrobromide is heated with 11.0 g of ammonium pivalate in 70 ml of dimethylformamide at 100°C. It is stirred for 9 hours at this temperature while introducing ammonia gas. The reaction solution is then evaporated in vacuo, the residue is dissolved in each 100 ml of water and ethyl acetate, and adjusted with 10 ml of 25% ammonia to pH 9. The organic phase is separated, and the alkaline water phase is extracted once with ethyl acetate. The combined organic phases are washed with water and evaporated after drying over sodium sulphate. The residue is dissolved hot in acetonitrile, and brought to crystallization while cooling. After filtration and redissolution from acetonitrile, 2-tert.-butyl-4(5)*phenyl-5(4)-(3-pyridyl)-imidazole is obtained, m.p. 190-191°C, yield 6.35 g (49.6 g of the theoretical).

The starting material can be prepared as follows:

To a solution of 84.9 g of benzyl-3-pyridyl ketones in 1200 ml of ethylene chloride, 72.2 g of bromine are added dropwise at 40°C over the course of 5 hours. It is then stirred for a further 3 hours at 40°C, then α-bromo-benzyl-3-pyridyl-ketone-hydro-bromide can be isolated by filtration (m.p. 226-230°C), yield 134.4g ( 87.6

% of the theoretical).

Example 3

17.8 g of α-bromo-benzyl-3-pyridyl ketone hydrobromide and 35.75 g of ammonium pivalate are dissolved in 75 ml of dimethylformamide and stirred for 3 hours at 100°C. Processing takes place as indicated in example 2. You get 2 .-tert. -butyl-4(5)-phenyl-5(4)-(3-pyridyl)-imidazole of m.p. 191-192°C, yield 8.13 g (58.7% of theory).

Example 4

4.09 g of pivalic acid are dissolved in 25 ml of dimethylformamide. After heating to 100°C, 2.9 g of ammonium carbonate are first added and then, after stirring for a few minutes, 2.41 g of α-bromo-benzyl-3-pyridyl ketone hydrobromide. During 9 hours, stirring is carried out at 100°C while a further 4.6 g of ammonium carbonate is simultaneously added in portions. The preparation takes place as described in example 2. 2-tert-butyl-4 (5)-phenyl-5 (4)-(3-pyridyl)-imidazole is obtained. Sm.p. 190.5-192°C.

Example- 5

32.85 g of α-bromo-benzyl-3-pyridyl-ketone hydrobromide is suspended in a solution of 56.4 g of pivalic acid and 100 ml of cellosolve. At;', weather or temperature, the pivalic acid is neutralized by the introduction of ammonia, then stirred for 3 hours at 1Q0°C.

The preparation takes place as described in example 2. 2-tert-butyl-4(5)-phenyl-5(4)-(3-pyridyl)-imidazole is obtained, m.p. 190.5-191°C.

Example- 6

To 23.35 g of benzyl-3-pyridyl-ketone hydrochloride i

210 g of pivalic acid are dripped at 85°C over the course of 4 hours with 17.0 g of bromine. It is then stirred for a further 3 hours at 90°C, then as much pivalic acid is distilled off under vacuum until there is also only 6 times the molar amount (referred to benzyl-3-pyridyl-ketone hydrochloride) in the reaction vessel. The reaction mixture containing α-bromo-benzyl-3-pyridyl-ketone hydrobromide and pivalic acid is diluted with 100 ml of cellosolve. At 10-15°C, the pivalic acid is now neutralized with ammonia gas, and the mixture is then stirred for 3 hours at 100°G. The work-up takes place as described in example 2. 2-tert-butyl-4(5)-phenyl-5(4)-(3-pyridyl)-imidazole of m.p. 1 90-1 90, 5°C, yield 16.33 g (59.0% of theory).

Example 7

23.3 g of benzyl-3-pyridyl ketone hydrochloride are suspended in 230 ml of pivalic acid at 85°C. 17 g of bromine are added dropwise over the course of 6 hours, the excess bromine is then driven off by the addition of 10 ml of acetone, and the reaction mixture is cooled to 6o°C.

Add 90 g of ammonium pivalate, stir

o

half an hour at 60°C, and then increase the temperature for 5 hours to 100°C. After cooling to 40°C, 200 ml of acetic acid ethyl ester and 50 ml of water are added, stirred until complete dissolution and then the mixture is poured into 100 ml of 10% hydrochloric acid. The organic phase is separated and washed twice with each time 50 ml of 10% hydrochloric acid and once with water.

The combined aqueous phases are brought to pH 8-9, then the separated crude product is taken up in acetic acid ethyl ester, and is obtained as an oil from this after washing with water and evaporation, which is brought to crystallization by absorption in 60 ml of acetonitrile. 8.5 g (30.6% of the theoretical) of 2-tert-butyl-4(5)-phenyl-5(4.)-3-pyridyl)imidazole are obtained, m.p. 191-192°C.

The starting material can, for example, be harvested. is prepared as follows: 21.9 g of benzyl-3-pyridyl-ketone hydrochloride (comp. example 1) is dissolved in 295 ml of water. After adding 94 ml of toluene, 14.2 ml of conc. ammonia. After separation of the toluene phase, the water phase is extracted

two more times with 20 ml of toluene each time, and evaporate the combined organic phases to dryness. Benzyl-3-pyridyl ketone is obtained, m.p. 60.2-61.5°C.

Example 8

Chlorine gas is introduced into a solution of 19.73 g of benzyl-3-pyridyl ketone and 200 ml of ethylene chloride at 80°C over the course of 13 hours. The α-chloro-benzyl-3-pyridyl-ketone hydrochloride can then be isolated by filtration fsm.p. 2 07, 4-21 0, 0°C ),

yield 18.3 g (68.2% of theoretical).

Example 1 9

30.0 g (0.084 mol) of α-bromo-benzyl-3-pyridyl-ketone hydrobromide is heated with 60.0 g of ammonium valerianate in 150 ml of cellosolve at 100°C. It is stirred for 3 hours at this temperature, then the reaction mixture is evaporated. The preparation takes place as in example 1. 2-n-butyl-4(5)-phenyl-5(4)-(3-pyridyl)-imidazole is obtained from m.p. 11 7.5-11 9.5°C, yield 12.0 g (51.5% of theory).

Example 10

18.3 g of α-chloro-benzyl-3-pyridyl-ketone hydrochloride id

and 48.6 g of ammonium pivalate are suspended in 120 ml of ethylene glycol monoethyl ether and stirred for 3 hours at 100°C. Processing takes place as in example 2. You get 2-t ert.-4 (5 )-f e nyl-5 (4 ) -

(3-pyridyl)-imidazole of m.p. 190.5-191, 5°Q.

Ex e mp el 1 1

27.5 g of α-bromo-deoxybenzoin is heated with 42.4 g of ammonium acetate in 100 ml of ethylene glycol monoethyl ether for 4 hours at 100UC. One filters from undissolved, evaporates the filtrate in vacuo, and takes up the residue with 100 ml of water and 100 ml of ethyl acetate.

The pH is adjusted with aqueous ammonia at 9-10, separated

the organic phase and washes it with water. After evaporation, a crystalline residue remains which is taken up with a little cold methanol and filtered off.

12.8 g (54.7% of the theoretical) of 2-methyl-4,5-diphenylimidazole are obtained, which can be recrystallized from methanol, m.p. 237-238°C.

Example 12

Analogous to example 11, 23.0 g of ct-chloro-deoxybenzoin is reacted with 42.4 g of ammonium acetate. 12.1 g (51.7% of the theoretical) of 2-methyl-4,5-diphenyl-imidazole are obtained.

Example T3

Analogously to examples 1 to 9, one obtains: 2-(p-chlorophenyl)-4 (5)-(p-methoxyphenyl)-5 (4)-(3-pyridyl)-imidazole, m.p. 200-3°C,

2-tert-butyl-4(5)-(p-methoxyphenyl)-5(4)-(3-pyridyl)-imidazole, m.p. 2Q2-4°C,

2-tert-butyl-4(5)-(p-chlorophenyl)-5(4)-(3-pyridyl)-imidazole, m.p. 205-6°C>>

2-tert-butyl-4(5)-(m-tolyl)-5(4)-(3-pyridyl)-imidazole, m.p. 170-1°C,

2-tert-butyl-4(5)-(p-methylthiophenyl)-5(4)-(3-pyridyl)-imidazole, m.p. 1 99-200°C,

2-tert-butyl-4(5)-(p-methoxyphenyl)-5(4)-(3-pyridyl-1-oxido)-imidazole, m.p. 250-8°C, and

2-trifluoromethyl-4, 5-bis(p-methoxyphenyl)-imidazole, m.p. 1 92-1 94°C, 2-tert,-butyl-4, 5-bis-phenyl-imidazole.

Example 14

Analogous to examples 1-12, you get

2-isobutyl-4, 5-bis-phenyl-imidazole, m.p. 211-214°C, 2-(g-bromophenyl)-4,5-bis-phenyl-imidazole, m.p. 262-264 C and

5-methyl-2,4-bis-phenyl-imidazole, m.p. 214-215°C.

Claims (10)

1. Process for the preparation of imidazoles with formula in which R., as well as at least one of the residues R2 and R^ means an organic residue bonded over a carbon atom, and a different residue R2 or R^ means hydrogen, with non-aromatic residues R2 and R^ bonded over saturated carbon atoms also may be connected to each other, with the precaution that R^ is different from residues of the formula -A-O-R^ , -A-S(0)n -R^ and -A-R^ , in which A means a divalent hydrocarbon residue, R^ means a possibly substituted hydrocarbon residue , n means 0, 1 or 2 and R,- means possibly esterified or amidated carboxy, when R2 and R^ mean aromatic residues, as well as their salts, characterized in that a reactive esterified hydroxyketone with formula in which X means a reactive esterified hydroxy group, or a salt thereof, is reacted with an ammonium salt of the formula if necessary in the presence of ammonia or an ammonia releasing agent. 2. Method according to claim 1, characterized in that the starting point is a compound of formula IX, in which X means hydroxy, esterified with a strong mineral acid or strong organic sulfonic acid, such as hydroxy, esterified with a halogen hydrogen acid, e.g. chloric or hydrobromic acid, or a lower alkane or arylsulphonic acid, such as methanesulphonic acid or an optionally substituted benzenesulphonic acid. 3. Method according to one of the claims: 1 and 2, characterized in that a compound of formula IX is reacted with approximately equimolar amounts of an ammonium salt of formula X, and the least equimolar amount preferably, however, the approx. 3 to 5-fold molar amount of ammonia or a minimum molar excess of the salt of formula X or an ammonium salt a weaker acid compared to the acid of formula -C00H (XI), e.g. with ammonium carbonate or ammonium carbamate, as ammonia releasing agent. 4. Method according to one of claims 1-3" characterized in that a compound of formula IX is reacted with at least twice the amount of an ammonium salt of formula X. 5. Method according to one of claims 1 and 2, characterized in that a compound of formula IX is reacted, in which X means halogen, such as bromine, a reaction temperature of about 100°C with an ammonium salt of formula X in excess, e.g. eg in a ratio to the ester of formula IX from about 4:1 to about 6:1. 6. Method according to one of the claims 1=5, characterized in that ammonium salt with formula X is formed under the reaction conditions as the reaction mixture contains the acid with formula R^ -COOH (XI) is mixed with liquid or gaseous ammonia to form an acid with formula R^ -C00H (XI) is reacted with ammonia or an ammonium salt of a weaker acid in relation to the acid with formula R^ -COOH (XI), such as carbonic acid, e.g. with ammonium carbonate or carbamate. 7. Method according to one of claims 1-6, characterized in that the corresponding acid of formula R 1 -COOH (XI) is used as solvent, possibly in excess. 8. Process according to one of the claims 1-7, characterized in that imidazoles of formula I are prepared, in which R 1 means lower alkyl, cycloalkyl or optionally with lower alkyl, lower alkoxy or halogen substituted phenyl, one of the residues: R 2 and R, optionally means with lower alkyl, lower alkoxy, lower alkylthio, lower alkanesulfonyl," hydroxy or halogen substituted phenyl and on the other means optionally N-oxidized 6-membered heteroaromatic residue with 1 or 2 nitrogen atoms, as well as their salts. 9. Process according to one of the claims 1-7, characterized in that imidazoles of formula I are prepared, in which R^ means a branched lower alkyl radical with up to and including 4 C atoms, or one optionally with halogen up to and including atomic number 3-5, as chlorine, substituted phenyl radical, at least one of the radicals R 2 and R 2 means one with halogen up to and including atomic number 35 lower alkyl up to and including 4 C atoms) lower alkoxy with up to and including 1 C atoms, or lower alkylthio with up to and including 4 C- atoms such as methylthio, p-substituted, with lower alkoxy with up to 4 C atoms such as methoxy, m- and p-substituted or with halogen with atomic number up to and including 35 as chlorine, o- and p-substituted phenyl residue and a different residue R 1 or R 2 means pyridyl or 1-oxido-pyridyl such as 3-pyridyl, furyl, such as 2-furyl or thienyl, such as 2-thienyl, as well as their salts. 10. Method according to one of claims 1 to 12, characterized in that one of the compounds of formula I mentioned from examples 1 to 10 is prepared, especially 2-tert.-butyl-4(5)-phenyl-5(4)- (3-pyridyl)-imidazole or a salt thereof.