Imidazole carboxylic acids and derivatives thereof

Benzhydryl-imidazole derivatives having carboxyl functions in the imidazole ring have valuable properties in plant protection and growth regulation in agriculture and horticulture. They are also effective as antimycotis, fungicides and herbicides and can be used for combating plant-pathogenic bacteria.

German Offenlegungsschrift No. 2,130,673 describes benzhydrylimidazole 
derivatives carrying alkyl substituents in the imidazole ring. 1-Benzyl- 
and 1-tetrahydronaphthyl-imidazole (5)-carboxylic acids and their esters 
are also known (J. Med. Chem. 15, 336-337 (1972)). Benzhydryl-imidazole 
derivatives having carboxyl functions in the imidazole ring have not yet 
become known. 
It has now been found that compounds of this type have valuable properties 
in plant protection and growth regulation. 
The present invention therefore provides compounds of the formulae 
##STR1## 
in which m is zero, 1 or 2, 
n is 1 or 2, and 
m+n is equal to or smaller than 3; 
R is halogen, (C.sub.1 -C.sub.6)alkyl, allyl, hydroxy(C.sub.1 
-C.sub.6)alkyl, halo(C.sub.1 -C.sub.6)alkyl, thiol, (C.sub.1 
-C.sub.6)alkylthio, cyano, phenyl or phenyl(C.sub.1 -C.sub.2)alkyl; 
R.sub.1 is hydroxy, (C.sub.1 -C.sub.6)alkoxy, hydroxy(C.sub.2 
-C.sub.6)alkoxy, (C.sub.2 -C.sub.6)alkoxyalkoxy, di(C.sub.1 
-C.sub.3)alkylphosphinyl-(C.sub.1 -C.sub.3)alkoxy, di(C.sub.1 
-C.sub.3)alkylphosphinyl-(C.sub.2 -C.sub.3)hydroxyalkoxy, amino, (C.sub.1 
-C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 
-C.sub.3)alkylamino(C.sub.1 -C.sub.3)alkylamino, hydroxyamino, (C.sub.1 
-C.sub.3)alkoxyamino; N-(C.sub.1 -C.sub.3)-alkyl-N-(C.sub.1 
-C.sub.3)-alkoxyamino, anilino, N-pyrrolidino, N-piperidino, N-morpholino, 
hydrazino, N'-(C.sub.1 -C.sub.3)-alkylhydrazino, N',N'-dimethylhydrazino 
or N'-phenylhydrazino, 
R.sub.2 and R.sub.3, which may be identical or different, are hydrogen, 
halogen, (C.sub.1 -C.sub.3)alkyl, trifluoromethyl, hydroxy, (C.sub.1 
-C.sub.3)alkoxy, halo (C.sub.1 -C.sub.3)alkoxy, (C.sub.1 
-C.sub.3)alkylthio, cyano, nitro or acetamino, and 
R.sub.4 is hydrogen or phenyl, 
and the non-toxic salts thereof with acids or bases. 
In the compounds of formulae I and II preferred halogens are chlorine or 
bromine. The salts of the compounds are preferably the acid salts with 
mineral acids such as nitric acid, hydrochloric acid, sulfuric acid, or 
phosphoric acid, or alkali metal (Na, K) or ammonium salts. Alkaline earth 
metal salts or salts with organic bases such as triethylamine are also 
effective. 
The compounds according to the invention can be prepared by a great variety 
of processes, for example by (a) reacting a compound of the formula 
##STR2## 
in which R.sub.5 is formyl or acetyl 
R.sub.6 is (C.sub.1 -C.sub.6)alkyl 
R.sub.7 is hydrogen or (C.sub.1 -C.sub.6)alkoxycarbonyl and Cat is an 
alkali metal cation, with thiocyanic acid and, if desired, in the 
2-thio-imidazole of the formula 
##STR3## 
(a.sub.1) dehydrating the SH group in 2-position of the imidazole ring to 
form a --S--S--(disulfide) bridge or 
(a.sub.2) eliminating the SH-group in 2-position of the imidazole ring by 
desulfurization, optionally followed by halogenation or 
hydroxy-methylation in 2-position, or 
(b) reacting a compound of the formula 
##STR4## 
in which R.sub.8 is hydrogen or (C.sub.1 -C.sub.3)alkyl and R' has the 
meaning of R except that R' is not a --SH group, with a compound of the 
formula 
##STR5## 
in which X is halogen or an alkyl or arylsulfonyl group and then splitting 
off the group --CO--R.sub.8 in known manner, or 
(c) reacting a compound of the formula 
##STR6## 
in which Y is hydrogen, an alkali metal or a silver atom with a compound 
of the formula VI, or 
(d) reacting a compound of the formula 
##STR7## 
with a compound of the formula 
##STR8## 
or 
(e) reacting a compound of the formula 
##STR9## 
in which A is a trimethylsilyl or halomagnesium group, with a compound of 
the formula 
##STR10## 
in which B is halogen or hydroxy, or 
(f) oxidizing a compound of the formula 
##STR11## 
in which R" has the same meaning as R except that it is not --SH-- or 
(C.sub.1 -C.sub.6)alkylthio, and R.sub.9 is --CH.sub.2 OH or --CHO, or 
(g) hydrolizing in a compound of the formula 
##STR12## 
the --CN--group(s) to yield carboxyl group(s) or acide amide group(s) and, 
if desired, in the compounds obtained by reactions (a) to (g) 
transesterifying or saponifying the ester groups and/or transforming the 
free acids obtained into non-phytotoxic salts, esters, thioesters, amides, 
anilides, or hydrazides and, in the case of several ester groups being 
present, thermally splitting off one of them. 
In the following the manufacturing processes are described in further 
detail. 
(a) The starting compounds of formula III can be prepared by reacting 
benzhydryl amine with chloroacetic acid ester to yield 
N-benzhydryl-glycine ester, formylating or acetylating the latter at the 
nitrogen atom and further reacting the N-acyl compound obtained with 
formic acid ester (R.sub.7 =H) or oxalic acid ester (J. Am. Chem. Soc. 71, 
644 (1949)). The cyclization with thiocyanic acid takes place smoothly in 
an inert aqueous system, for example water or a mixture of water and 
tetrahydrofurane, at temperatures between about 50.degree. C. and the 
boiling point of the solvent. 
In this manner compounds of formula I are obtained which contain hydrogen 
or a carbalkoxy group in 4-position of the imidazole ring and a 
--SH--group in 2-position. The latter can be dehydrogenated in known 
manner, for example by means of iodine, oxygen, hydrogen peroxide or 
sulfuryl chloride, whereby disulfides of the formula III are obtained. 
Alternatively, the SH group can be removed by desulfurization from the 
compounds obtained in the first place, for example with 15% nitric acid at 
30.degree. to 35.degree. C. or with nickel at 50.degree. to 100.degree. C. 
The desulfurized compounds can then be halogenated or hydroxymethylated in 
known manner. The hydroxymethyl group can be introduced, for example, by 
using a formaldehyde solution in methanol or water at elevated 
temperatures, preferably at 130.degree. to 140.degree. C., in an 
autoclave. 
(b) In this reaction the --CO--R.sub.8 group has the function of a 
protective group to prevent a double reaction at both nitrogen atoms of 
the imidazole ring. The starting compounds of formula V can be prepared by 
acylating compounds of the formula VIII at the nitrogen atom 1. The 
reaction of a compound of the formula V with a compound of the formula VI 
results in a quaternization at the nitrogen atom 3. The subsequent 
splitting off of the acyl group by hydrolysis, alcoholysis or aminolysis, 
which takes place very readily, yields in known manner the desired 
compounds of the formula I (Rec. Trav. Chim. Pays-Bas 93 (1974), page 56). 
In formula VI X stands for a group which makes possible the quaternization 
of the imidazole ring. A preferred group of this type is halogen (Cl, Br), 
or an alkyl or arylsulfonyl group (mesyl, tosyl). 
The reaction of compound V with compound VI is generally carried out at a 
temperature of from 60.degree. to 100.degree. C. in a suitable solvent 
such as acetonitrile or propionitrile. 
(c) This reaction corresponds to process (b) with the exception that the 
second nitrogen atom of the imidazole ring is not protected. In order to 
avoid a double reaction (especially when Y is hydrogen) it is advantageous 
to carry out the reaction in the presence of a tertiary amine, for example 
triethyl amine or N-ethyldiisopropyl amine in a solvent such as 
acetonitrile, dimethyl formamide, dimethyl sulfoxide, chloroform, carbon 
tetrachloride, at a temperature of from 20.degree. to 85.degree. C. 
(d) Water is split off according to process (d) preferably at a temperature 
of from 130.degree. to 150.degree. C. in an inert solvent such as xylene 
or mesitylene, optionally in the presence of catalytic amounts of 
aluminium oxide. 
(e) The reaction according to (e) takes place at low temperatures in the 
range of from 0.degree. C. to room temperature or a little thereabove. 
Preferred solvents are anhydrous benzene, toluene, tetrahydrofurane, or 
dioxane. 
(f) The starting compounds of the formula XII can be prepared according to 
the process described in J. Am. Chem. Soc. 71 (1949), pages 2801-03, from 
correspondingly substituted starting compounds. The oxidation is carried 
out in known manner with a usual oxidation agent, for example potassium 
permanganate, hydrogen peroxide, chromium trioxide, tert. butyl chromate, 
nickel peroxide, silver oxide, or manganese dioxide, at a temperature of 
from 0.degree. to 35.degree. C. Suitable solvents are ketons such as 
acetone or methyl ethyl ketone, acetic acid, dimethyl sulfoxide and water. 
(g) The addition of water to nitrile groups yields either carbonamides or 
carboxylic acids, depending on the reaction conditions. To obtain 
carbonamides the components are allowed to react at 20.degree. to 
50.degree. C. in about 1 N sodium hydroxide solution, optionally in the 
presence of catalytic amounts of hydrogen peroxide. Carboxylic acids are 
obtained by saponifying the nitrile group(s) with about 6 N sodium 
hydroxide solution at 70.degree. to 100.degree. C. The starting compounds 
of formula XIII are obtained, for example, according to the process 
described in Bull. Chem. Soc. Japan 41 (1968), pages 1237-40, from 
correspondingly substituted starting compounds. 
The compounds obtained according to processes (a) to (g) can be modified in 
many ways at the --CO--R.sub.1 group(s). Thus, esters can be saponified in 
known manner to give the free acids or the salts thereof. The free acids 
as obtained according to processes (a) to (f) by saponification of ester 
groups or according to process (g) by hydrolysis of cyano groups can be 
transformed, optionally via the acid chlorides, into other esters, 
thioesters, amides, anilides, or hydrazides of the formula --CO--R.sub.1. 
In compounds containing two ester groups one of them can be saponified and 
decarboxylated. Processes of this type are known to the expert and need 
not be described in further detail.

The following examples illustrate the invention. 
EXAMPLE 1 
(a) 1-Benzhydryl-2-mercapto-5-methoxycarbonyl-imidazole 
31.3 g (0.1 mol) of 2-benzhydrylformyl)-amino-3-oxopropionic acid methyl 
ester (prepared by formylation of (benzhydrylformyl)-aminoacetic acid 
methyl ester according to J. Am. Chem. Soc. 71, (1949), page 644, and 18 g 
of potassium thiocyanate were introduced into a mixture of 200 cc of 
tetrahydrofurane, 200 cc of water and 16.5 cc of 36% aqueous hydrochloric 
acid while stirring. Stirring was continued for 31/2 hours at 40.degree. 
C.; then the organic phase was separated and the solvent removed under 
reduced pressure. The residue was taken up in methylene chloride and freed 
from acid residues by shaking twice with water. After washing with 
methanol, 29.8 g (92% of the theory) of 
1-benzhydryl-2-mercapto-5-methoxy-imidazole melting at 194.degree. C. were 
obtained. 
In analogous manner the following compounds were prepared: 
(1b) 1-(4'-chlorodiphenylmethyl)-2-mercapto-5-methoxycarbonyl-imidazole, 
m.p. 184.degree. C.; 
(1c) 1-(4'.methyldiphenylmethyl)-2-mercapto-5-methoxycarbonyl-imidazole, 
m.p. 186.degree. C. 
EXAMPLE 2 
(a) 1-Benzhydryl-2-mercapto-5-imidazole-carboxylic acid 
3.2 g (0.01 mol) of 1-benzhydryl-2-mercapto-5-methoxycarbonyl-imidazole 
(Example 1a) and 20 cc of 1 N sodium hydroxide solution were heated for 3 
hours to 80.degree. C. whereby the disodium salt of 
1-benzhydryl-2-mercapto-5-imidazole-carboxylic acid was obtained in 
practically quantitative yield (3.5 g). The salt decomposed at a 
temperature above 255.degree. C. Crystalline 
1-benzhydryl-2-mercapto-5-imidazole-carboxylic acid, m.p. 158.degree. C., 
was obtained by dissolving the salt in water and acidifying the solution 
with 2 N hydrochloric acid. 
In an analogous manner the following compounds were prepared: 
(2b) 1-(4'-chlorodiphenylmethyl)-2-mercapto-5-imidazolecarboxylic acid, 
m.p. 153.degree. C.; 
(2c) 1-(4'-methyldiphenylmethyl)-2-mercapto-5-imidazolecarboxylic acid, 
m.p. 140.degree. C. 
EXAMPLE 3 
(a) 1-Benzhydryl-2-mercapto-5-propoxycarbonyl-imidazole 
3.1 g (0.01 mol) of 1-benzhydryl-2-mercapto-5-imidazole carboxylic acid 
(Example 2a) and 100 cc of 1-propanol were heated to 97.degree. C. while 
introducing gaseous hydrogen chloride until esterification was completed. 
Working up in a basic medium yielded 3.3 g (94% of the theory) of 
1-benzhydryl-2-mercapto-5-propoxycarbonyl-imidazole, m.p. 133.degree. C. 
In analogous manner the following compound was prepared: 
(3b) 1-benzhydryl-2-mercapto-5-ethoxycarbonyl-imidazole, m.p. 194.degree. 
C. 
EXAMPLE 4 
1-Benzhydryl-5-methoxycarbonyl-2-methylthio-imidazole 
3.2 g (0.01 mol) of 1-benzhydryl-2-mercapto-5-methoxycarbonyl-imidazole 
(Example 1a) were introduced into a mixture of 30 cc of water, 15 cc of 
methanol, 15 cc of methylene chloride, 10 cc of 2 N sodium hydroxide 
solution and 1.3 cc of methyl iodide. Stirring was continued for 30 
minutes. During this time the temperature of the reaction mixture rose to 
39.degree. C. After cooling, 3 g (90% of the theory) of 
1-benzhydryl-5-methoxycarbonyl-2-methylthio-imidazole, m.p. 118.degree. C. 
were isolated from the organic phase. 
EXAMPLE 5 
1-Benzhydryl-2-mercapto-5-imidazole-carboxylic acid pyrrolidide 
In a nitrogen atmosphere 3.2 g (0.01 mol) of 
1-benzhydryl-2-mercapto-5-methoxycarbonyl-imidazole (Example 1a) and 60 cc 
of pyrrolidine were refluxed for 3 days. Excess pyrrolidine was then 
removed in vacuo and the 1-benzhydryl-2-mercapto-5-imidazole-carboxylic 
acid pyrrolidine obtained was recrystallized from methanol (m.p. 
263.degree. C.). The yield was 3.3 g (91% of the theory). 
EXAMPLE 6 
Bis(1-benzhydryl-5-methoxycarbonyl-imidazolyl(2))-disulfide 
A 10% aqueous potassium iodide-iodine solution was added to a solution of 
3.2 g (0.01 mol) of 1-benzhydryl-2-mercapto-5-methoxycarbonyl-imidazole 
(Example 1a) in 60 cc of 2 N sodium hydroxide solution until the 
precipitate formation was completed. The precipitate was isolated, washed 
with water and transferred into a separating funnel containing 250 cc of 
carbon tetrachloride and 50 cc of a 5% aqueous sodium hydrogen sulfite 
solution. The organic phase was separated, dried and concentrated, 
yielding 3.0 g (95% of the theory) of 
bis(1-benzhydryl-5-methoxycarbonyl-imidazolyl(2))-disulfide in crystalline 
form, m.p. 154.degree. C. 
EXAMPLE 7 
Bis(1-benzhydryl-5-carboxyl-imidazolyl(2))-disulfide 
3.2 g (0.005 mol) of 
bis(1-benzhydryl-5-methoxycarbonyl-imidazolyl(2))-disulfide (Example 6) 
were saponified at 80.degree. C. with the equivalent amount of 2 N sodium 
hydroxide solution. The cooled reaction mixture was acidified with 
hydrochloric acid, 3.0 g (96% of the theory) of 
bis(1-benzhydryl-5-carboxyl-imidazolyl(2))-disulfide, m.p. 180.degree. C. 
with decomposition were obtained. 
EXAMPLE 8 
(a) 1-Benzhydryl-5-methoxycarbonyl-imidazole 
325 cc of 15% nitric acid and 1.6 g of sodium nitrite were added while 
stirring to 325 cc of methylene chloride. 32.5 g (0.1 mol) of 
1-benzhydryl-2-mercapto-5-methoxycarbonyl-imidazole (Example 1a) were then 
added in portions at 35.degree. C. while stirring. Stirring at 35.degree. 
C. was continued for a further 30 minutes, the reaction mixture was cooled 
to 10.degree. C. and the crystallized 
1-benzhydryl-5-methoxycarbonyl-imidazole nitrate was filtered off with 
suction. The crystals were freed from acid residues by means of ice water 
and dried under reduced pressure at 30.degree. C., m.p. 175.degree. C. 
with decomposition. 
From the washed and neutralized methylene chloride phase 9.2 g (32% of the 
theory) of 1-benzhydryl-5-methoxycarbonyl-imidazole, melting at 
129.degree. C., were obtained. 
For transformation into the free base the nitrate was suspended in 100 cc 
of chloroform and the total amount of the nitrate was dissolved by adding 
about 60 cc of 1 N sodium hydroxide solution. From the chloroform solution 
17.8 g (61% of the theory) of 1-benzhydryl-5-methoxycarbonyl-imidazole 
were isolated. 
In analogous manner the following compounds were prepared from 
1-(4-chlorodiphenylmethyl)-2-mercapto-5-methoxycarbonyl imidazole (Example 
1b): 
(8b) 1-(4'-chlorodiphenylmethyl)-5-methoxycarbonyl-imidazole, m.p. 
94.degree. C.; 
(8c) 1-(4'-methyldiphenylmethyl)-5-methoxycarbonyl-imidazole, m.p. 
85.degree. C. 
EXAMPLE 9 
1-Benzhydryl-5-methoxycarbonyl-imidazole hydrochloride 
1 g of 1-benzhydryl-5-methoxycarbonyl-imidazole (Example 8) was dissolved 
in 45 cc of diethyl ether. The 1-benzhydryl-5-methoxycarbonyl-imidazole 
hydrochloride was obtained by adding ethereal hydrochloric acid. The 
compound melted at 136.degree. C. 
EXAMPLE 10 
1-Benzhydryl-2-hydroxymethyl-5-methoxycarbonyl-imidazole 
2.9 g (0.01 mol) of 1-benzhydryl-5-methoxycarbonyl-imidazole (Example 8) 
and 25 cc of 50% methanolic formaldehyde solution were heated for 36 hours 
to 135.degree. C. 3.15 g of 
1-benzhydryl-2-hydroxymethyl-5-methoxycarbonyl-imidazole, m.p. 160.degree. 
C., were obtained from the reaction mixture in an almost quantitative 
yield. 
EXAMPLE 11 
(a) 1-Benzhydryl-5-imidazole-carboxylic acid 
2.9 g (0.01 mol) of 1-benzhydryl-5-methoxycarbonyl-imidazole (Example 8) 
were saponified at 80.degree. C. with an equivalent amount of 1 N sodium 
hydroxide solution. The sodium salt of 1-benzhydryl-5-imidazole-carboxylic 
acid obtained melted at 176.degree. C. The desired 
1-benzhydryl-5-imidazole-carboxylic acid, m.p. 216.degree. C., was 
obtained by acidifying the aqueous solution of the sodium salt with 
hydrochloric acid. Yield 2.64 g (95% of the theory). 
The following compounds were prepared in an analogous manner from 
1-(4'-chlorodiphenylmethyl)-5-methoxycarbonyl-imidazole (according to 
Example 6b): 
(11b) 1-(4'-chlorodiphenylmethyl)-5-imidazole-carboxylic acid, m.p. 
135.degree. C.; 
(11c) 1-(4'-methyldiphenylmethyl)-5-imidazole-carboxylic acid, m.p. 
202.degree. C. 
The following compounds were prepared from the dried sodium salt of 
1-benzhydryl-5-imidazole-carboxylic acid (Example 11a): 
(11d) 1-benzhydryl-5-n-butoxycarbonyl-imidazole, m.p. 53.degree. C. by 
reaction with n-butyl bromide; 
(11e) 1-benzhydryl-5-benzyloxycarbonyl-imidazole, m.p. 104.degree. C. by 
reaction with benzyl chloride. 
EXAMPLE 12 
(a) 1-Benzhydryl-5-propoxycarbonyl-imidazole 
Gaseous hydrochloric acid was introduced into 2.8 g (0.01 mol) of 
1-benzhydryl-5-imidazole carboxylic acid (according to Example 11) in 140 
cc of 1-propanol while refluxing the mixture until the esterification was 
completed. The hydrochloride formed was neutralized and yielded 3.1 g (96% 
of the theory) of 1-benzhydryl-5-propoxycarbonyl-imidazole, m.p. 
81.degree. C. 
The following compounds were prepared in analogous manner: 
(12b) 1-benzhydryl-5-ethoxycarbonyl-imidazole, m.p. 92.degree. C.; 
(12c) 1-benzhydryl-5-butoxycarbonyl-imidazole, m.p. 53.degree. C.; 
(12d) 1-benzhydryl-5-benzoyloxycarbonyl-imidazole, m.p. 104.degree. C. 
EXAMPLE 13 
1-Benzhydryl-5-propoxycarbonyl-imidazole 
The compound was prepared by transesterification of 2.9 g (0.01 mol) of 
1-benzhydryl-5-methoxycarbonyl-imidazole of Example 8. To this end it was 
refluxed for some time in 100 cc of propanol and in the presence of 
catalytic amounts of toluene sulfonic acid. The colorless crystals 
obtained had a melting point of 81.degree. C. 
EXAMPLE 14 
(a) 1-benzhydryl-5-(dimethylphosphinylmethoxycarbonyl)-imidazole 
3.0 g (0.01 mol) of the sodium salt of 1-benzhydryl-5-imidazole-carboxylic 
acid (Example 11) and 1.8 g of chloromethyl dimethyl phosphine oxide were 
heated with 40 cc of dimethyl formamide to 120.degree. C. under a nitrogen 
atmosphere until the reaction was completed. The solvent was removed under 
reduced presure and insoluble sodium chloride was separated by taking up 
the residue in acetone. Crystallization yielded colorless crystals melting 
at 174.degree. C., Yield 3.2 g (88% of the theory). 
The following compounds were prepared in analogous manner: 
(14b) 1-benzhydryl-5-(3-(dimethylphosphinyl)-propoxycarbonyl)-imidazole, 
m.p. 78.degree. C., with the use of 3-chloropropyl dimethyl phosphine 
oxide; 
(14c) 
1-benzhydryl-5-(2-dimethylphosphinyl-2-hydroxyethoxycarbonyl)-imidazole, 
m.p. 197.degree. C., with the use of 1-dimethylphosphinyl 2-chloroethanol; 
and 
(14d) 
1-benzhydryl-5-(2-dimethylphosphinyl-2-hydroxypropoxy-carbonyl)-imidazole, 
m.p. 89.degree. C., with the use of 2-dimethylphosphinyl 
1-chloropropanol(2). 
EXAMPLE 15 
(a) 1-Benzhydryl-5-hydrazinocarbonyl-imidazole 
2.9 g (0.01 mol) of 1-benzhydryl-5-methoxycarbonyl-imidazole (Example 8) in 
10 cc of methanol and 0.8 cc of hydrazine hydrate were refluxed for some 
time. After cooling, 2.9 g of benzhydryl-5-hydrazinocarbonyl-imidazole, 
melting at 152.degree. C. were isolated. 
The following compounds were prepared in analogous manner: 
(15b) 1-benzhydryl-5-(N',N'-dimethylhydrazinocarbonyl)-imidazole, m.p. 
211.degree. C.; 
(15c) 1-benzhydryl-5-(N'-methylhydrazinocarbonyl)-imidazole, m.p. 
123.degree. C.; 
(15d) 1-benzhydryl-5-hydrazinocarbonyl-2-mercapto-imidazole, m.p. 
222.degree. C. 
EXAMPLE 16 
(a) Benzhydryl-5-imidazole-carboxylic acid pyrrolidide 
2.9 g (0.01 mol) of 1-benzhydryl-5-methoxycarbonyl-imidazole (Example 8) in 
15 cc of pyrrolidine were refluxed for 6 hours. Excess pyrrolidine was 
removed in vacuo and the residue dissolved in methylene chloride. By means 
of a silica gel column the 1-benzhydryl-5-imidazol-carboxylic acid 
pyrrolidide was freed from colored impurities. Yield 2.8 g (86% of the 
theory), m.p. 117.degree. C. 
The following compound was obtained in analogous manner: 
(16b) 1-benzhydryl-5-(2'-diethylaminoethylaminocarbonyl)-imidazole 
monohydrate, m.p. 60.degree. C. 
EXAMPLE 17 
(a) 1-Benzhydryl-5-imidazole carboxylic acid amide 
In an autoclave 2.9 g (0.01 mol) of 
1-benzhydryl-5-methoxy-carbonyl-imidazole and 300 cc of methanolic ammonia 
solution, saturated at 20.degree. C., were heated for 8 hours to 
120.degree. C. 2.7 g (96% of the theory) of 
1-benzhydryl-5-imidazole-carboxylic acid amide, m.p. 153.degree. C., were 
obtained. 
The following compound was prepared in analogous manner: 
(17b) 1-benzhydryl-2-mercapto-5-imidazole-carboxylic acid amide, m.p. 
131.degree. C. 
EXAMPLE 18 
1-Benzhydryl-2-mercapto-4,5-dimethoxycarbonyl-imidazole 
In the manner described in Example (1a) 36.9 g (0.01 mol) of 
2-(benzhydrylformyl)-amino-3-oxo-succinic acid dimethyl ester (prepared by 
reacting (benzhydrylformyl)-aminoacetic acid methyl ester with oxalic acid 
dimethyl ester in the presence of sodium methylate) were reacted with 18 g 
of potassium thiocyanate for 48 hours at 50.degree. C. The 
1-benzhydryl-2-mercapto-4,5-dimethoxycarbonyl-imidazole formed 
crystallized on adding hexane. Yield 33.2 g (87% of the theory), m.p. 
154.degree. C. 
EXAMPLE 19 
1-Benzhydryl-4,5-dimethoxycarbonyl-imidazole 
3.8 g (0.01 mol) of 
1-benzhydryl-2-mercapto-4,5-dimethoxy-carbonyl-imidazole (Example 17) in 
50 cc of methanol were refluxed for 4 hours in the presence of 400 mg of 
Raney nickel. The catalyst was separated and thoroughly washed with 
methanol. The combined filtrate were concentrated and 3.1 g (90% of the 
theory) of 1-benzhydryl-4,5-dimethoxy-carbonyl-imidazole, m.p. 93.degree. 
C., were obtained. 
EXAMPLE 20 
(a) 1-Benzhydryl-4,5-dimethoxycarbonyl-imidazole 
20.3 g of benzhydryl chloride were added dropwise to a suspension of 18.4 g 
(0.1 mol) of 4,5-dimethoxycarbonyl-imidazole in 60 cc of acetonitrile and 
14 cc of triethylamine and the reaction mixture was heated for 8 hours at 
80.degree. C. The solvent was then removed under reduced pressure and 
triethylammonium chloride was separated by washing with water. 30 g (85% 
of the theory) of 1-benzhydryl-4,5-dimethoxycarbonyl-imidazole, m.p. 
93.degree. C., were obtained. 
The following compound was obtained in analogous manner with the use of 
2-chlorotrityl chloride (=2-chlorotriphenylmethyl chloride): 
(20b) 1-(2'-chlorotrityl)-4,5-dimethoxycarbonyl-imidazole, m.p. 202.degree. 
C. 
EXAMPLE 21 
Potassium salt of 1-benzhydryl-2-imidazole-carboxylic acid 
2.64 g (0.01 mol) of 1-benzhydryl-2-hydroxymethyl-imidazole, m.p. 
174.degree. C. (prepared from 1-benzhydryl-imidazole and formaldehyde), 
were dissolved in 150 ml of acetone. While stirring at 5.degree. C. a 
solution of 1.7 g of potassium permanganate in 120 cc of acetone was added 
dropwise. After 2 hours the solvent was removed under reduced pressure, 
the residue was stirred with 150 cc of chloroform and 150 cc of water and 
the separated manganese dioxide was filtered off. Crystalline potassium 
salt of 1-benzhydryl-2-imidazole-carboxylic acid was obtained from the 
chloroform phase. The salt decomposed at a temperature above 280.degree. 
C. 
1-Benzhydryl-2-imidazole-carboxylic acid 
The potassium salt obtained according to Example 20 was stirred with 0.1 N 
hydrochloric acid yielding fine needles of 
1-benzhydryl-2-imidazole-carboxylic acid, m.p. 191.degree. C. (about 70% 
of the theory). 
EXAMPLE 22 
1-Benzhydryl-5-methoxycarbonyl-imidazole 
1.7 g (0.01 mol) of 1-acetyl-4-methoxycarbonyl-imidazole in 5 cc of 
acetonitrile and 2 g of benzhydryl-chloride were refluxed for 4 hours, the 
solvent was removed under reduced pressure and the residue was stirred 
with 15 cc of 0.5 N sodium acetate solution to split off the acetyl group. 
The 1-benzhydryl-5-methoxycarbonyl-imidazole, m.p. 129.degree. C., was 
recrystallized from chloroform. 
EXAMPLE 23 
(a) 1-Benzhydryl-4,5-imidazole-dicarboxylic acid 
2.9 g (0.01 mol) of 1-benzhydryl-4,5-imidazole-dinitrile were thoroughly 
saponified with an equivalent amount of 3 N sodium hydroxide solution. On 
acidification of the solution 2.7 g (85% of the theory) of 
1-benzhydryl-4,5-imidazole-dicarboxylic acid, m.p. 194.degree. C., were 
obtained. 
(23b) In an analogous manner 1-(2'-chlorotrityl)-4,5-imidazole-dinitrile, 
m.p. 270.degree. C. (with decomposition), was obtained from 
1-(2'-chlorotrityl)-4,5-imidazole-dicarboxylic acid. 
EXAMPLE 24 
1-Benzhydryl-5-methylthiocarbonyl-imidazole 
2.8 g (0.01 mol) of 1-benzhydryl-5-imidazole-carboxylic acid were 
transformed at 40.degree. C. with 4.5 cc of thionyl chloride into the 
hydrochloride of 1-benzhydryl-5-imidazole-carboxylic acid chloride, which 
was freed from residual thionyl chloride with the aid of methylene 
chloride. The crystalline hydrochloride was dissolved in 20 cc of 
tetrahydrofurane and was reacted overnight at 25.degree. C. with 1.4 g 
(0.02 mol) of sodium methylmercaptide while stirring. The solvent was 
removed under reduced pressure and replaced by 50 cc of methylene 
chloride. The solution of the thiomethyl ester was separated from the 
insoluble sodium chloride. When worked up with pentane the ester obtained 
from the solution in the form of an oily residue separated in crystal 
form. The 1-benzhydryl-5-methylthiocarbonyl-imidazole was obtained in a 
yield of 85% and had a melting point of 98.degree. C. 
The following compounds were obtained in analogous manner from 
1-benzhydryl-5-imidazole-carboxylic acid chloride hydrochloride: 
(24b) by reaction with sodium 2-methoxyethylate and subsequent 
acidification with HCl: 
1-benzhydryl-5-(2-methoxyethoxy)-carbonyl-imidazole hydrochloride, m.p. 
125.degree. C.; 
(24c) by reaction with hydroxyl amine hydrochloride and triethyl amine: 
1-benzhydryl-5-hydroxyaminocarbonyl-imidazole, m.p. 93.degree. C.; 
(24d) by reaction with diethylamino-ethylamino hydrochloride and 
triethylamine: 
1-benzhydryl-5-(2-diethylamino-ethylamino)-carbonyl-imidazole monohydrate, 
m.p. 60.degree. C.; 
(24e) by reaction with sodium propyl mercaptide and acidification with HCl: 
1-benzhydryl-5-n-propylthiocarbonyl-imidazole-hydrochloride, m.p. 
140.degree. C. 
EXAMPLE 25 
1-Benzhydryl-2-(4)-bromo-5-methoxycarbonyl-imidazole 
A solution of 1.6 g of bromine in 5 cc of carbon tetrachloride was added 
while stirring to 2.9 g (0.01 mol) of 
1-benzhydryl-5-methoxycarbonyl-imidazole and 1.4 g of finely pulverized 
potassium carbonate in 60 cc of carbon tetrachloride. The reaction mixture 
was refluxed for 6 hours, allowed to cool and the solution was decanted 
from the separated potassium bromide. The solvent was then replaced by 15 
cc of diisopropyl ether and the 
1-benzhydryl-2-(4)-bromo-5-methoxycarbonyl-imidazole was isolated in the 
form of slightly yellow crystals, m.p. 78.degree. C. Yield 3.0 g (82% of 
the theory). 
The compounds according to the invention can be used for various purposes 
in agriculture and horticulture. They are effective growth regulators, 
herbicides and fungicides. They can also be used for the control of moss, 
of plant-pathogenic bacteria and as antimycotics. 
The invention, therefore, also provides compositions to be used in 
agriculture and horticulture and as antimycotics, plant growth regulators 
and herbicides as well as for combating fungi and plant-pathogenic 
bacteria. 
For the manufacture of the compositions the active compounds of the 
invention are formulated in usual manner, either alone or in combination 
with other active compounds or fertilizers, to give powders, dusts, 
pastes, granules, solutions, foams, emulsions, and suspensions. For 
blending and diluting the active compounds solvents, liquefied gases, 
emulsifiers, dispersants, foam producing agents and solid carrier 
materials as known in the production of plant protecting agents can be 
used. 
The compounds of the invention can be applied in a wide concentration range 
of from about 0.00005 to 2%. In special cases they can be used in a higher 
concentration and even in the pure state, for example ground to microfine 
particles. When used as herbicides or growth regulators the concentration 
of active substance generally ranges from 0.01 to 5 kg per hectare. The 
active compounds of the invention are preferably used in the form of 20 to 
50% wettable powders containing the usual proportions of inert substances, 
dispersing agents, wetting agents and optionally adhesives; 15 to 30% 
emulsion concentrates, and 5% granules as well as dusts of varying 
concentration of active compound. Compositions for the treatment of 
mycoses of the skin generally contain from 0.5 to 2% of active compound. 
When used as growth regulators the compounds of the invention exhibit an 
excellent growth-retarding efficiency, for example in cereals, horse beans 
and lawns and in the germination test of linseed and oat. 
With the use of growth regulators the harvest can be facilitated and the 
crop yield increased while simultaneously the quality of the harvested 
crops is improved. By shortening and strengthening the stems of cereals 
the nutrient supply of the spikes is improved and storage losses can be 
reduced. Moreover, by the use of growth regulators the protein content in 
cereals and soybeans and the sugar content in sugar beets and sugar cane 
can be increased. Further fields of application are, for example, the 
optimization of the propagation by cuttings and of the leaf growth of 
tobacco plants. The growth of grass, herbs and bushes can be controlled so 
that the cultivation costs can be reduced. In special cases the use of 
mechanical harvest aids becomes possible by the use of growth regulators 
or the costs thereof are at least reduced. In the cultivation of 
ornamental plants the growth can be adpated to the qualitative and 
seasonal demands of the market. 
The compounds of the invention are further characterized by very good 
herbicidal properties, especially in pre-emergence application, against a 
large number of economically important weed grasses and dicotyledonous 
weeds. On the other hand, they are tolerated by some crop cultures such as 
cotton, maize, rape, and beans, and hence can be used in selective weed 
control. 
Still further, the compounds of the invention have an excellent and in some 
cases even systemic effect against phytopathogenic fungi and, hence are 
suitable for plant protection. They exhibit e.g. a good fungicidal effect 
against rust fungi, Phytophthora infestans, Plasmopara viticola, Venturia 
inaequalis, Phoma betae and Botrytis cinerea and also against skin fungi 
such as Trichophyton mentagrophytes and Microsporium canis. Particularly 
good is the fungicidal effect of the compounds against Piricularia oryzae 
and genuine types of mildew in cucumber, cereals (wheat and barley), 
apples and ornamental plants, and more especially against 
benzimidazole-resistant types of mildew. 
The fungicidal compositions can be formulated in usual manner, for example 
as dusts, wettable powders, dispersions, and emulsifiable concentrates. 
They preferably contain from 10 to 90% by weight of active matter in 
addition to the usual adhesives, wetting agents, dispersants, fillers, and 
carrier materials. 
EXAMPLE I (growth inhibition) 
Young plants of cereals in the three-leaf stage were sprayed to the drip 
off with preparations of active compounds. When the untreated control 
plants had grown to a height of about 55 cm, the growth increase of all 
plants was measured and the inhibition of growth was calculated in percent 
of the increase in length of the control plants. The results are listed in 
the following Table I. 100% means total stagnation of growth and 0% 
indicates a growth corresponding to that of the untreated control plants, 
i.e. no inhibition. 
TABLE I 
______________________________________ 
Inhibition of growth in cereals 
compound of 
concentration 
inhibition of growth in % 
Example (kg/ha) wheat barley rye 
______________________________________ 
6 2.5 25 28 40 
1.25 20 15 31 
8 a 2.5 41 36 42 
1.25 32 31 37 
comparison (2- 
2.5 31 10 10 
chloroethyl)-tri- 
methyl-ammonium 
1.25 28 0 0 
chloride 
______________________________________ 
EXAMPLE II (herbicidal effect) 
Weeds of several botanic families were sown in pots and treated in the 
pre-emergence process with compounds of the invention. The weeds were 
allowed to germinate and grow in the greenhouse. About 4 weeks after 
treatment the result was evaluated visually by the scheme according to 
Bolle (Table II). It can be seen that the tested compounds had a vey good 
effect against numerous weeds. 
TABLE II 
______________________________________ 
Evaluation scheme according to Bolle (Nachrichtenblatt des 
Deutschen Pflanzenschutzdienstes 16, 1964, 92-94) 
Damage in % in 
evaluation number 
weeds crop plants 
______________________________________ 
1 100 0 
2 97.5 to 100 0 to 2.5 
3 95 " 97.5 2.5 " 5 
4 90 " 95 10 " 15 
5 85 " 90 15 " 25 
6 75 " 85 15 " 25 
7 65 " 75 25 " 35 
8 32.5 " 65 35 " 67.5 
9 0 " 32.5 67.5 " 100 
______________________________________ 
The results of the visual evaluation are summarized in the following Tables 
III and IV. 
TABLE III 
______________________________________ 
Biological effect against important monocotyledonous 
and dicotyledonous weeds in a pre-emergence trial 
Com- 
pound dose 
of (kg type of plant 
Ex. AS/ha) 1 2 3 4 5 6 7 8 9 10 
11 
______________________________________ 
2.5 -- 3 1 1 1 1 1 1 3 1 
1 
1 a 0.6 -- 4 1 1 2 1 1 1 4 1 1 
2.5 4 2 1 1 1 2 1 1 3 1 1 
8 a 0.6 4 2 1 1 1 2 1 1 3 1 1 
2.5 -- 2 1 1 2 2 1 1 -- 1 1 
6 0.6 -- 3 1 1 3 5 1 1 -- 4 1 
______________________________________ 
legend: 
1 Avena 
2 Alopecurus 
3 Setaria 
4 Poa 
5 Cyperus 
6 Lolium 
7 Digitaria 
8 Echinochloa 
9 Chrysanthemum 
10 Stellaria 
11 Amaranthus 
AS = active substance 
EXAMPLE III (fungicidal effect) 
In the following examples the letters A to E indicate the following 
comparative compounds: 
A: methyl-1-(butylcarbamoyl)-2-benzimidazole carbamate (Benomyl) 
B: N-tridecyl-2,6-dimethyl-morpholine (Tridemorph) 
C: 2,4-dinitro-6-sec. butyl-phenyl-3,3-dimethyl-acrylate (Binapacryl) 
D: O-ethyl-S,S-diphenyl-dithio-phosphate (Edifenfos) 
E: Polyoxine 
Wheat plants in the three-leaf stage were strongly infested with conidia of 
wheat mildew (Erysiphe graminis) and kept in a greenhouse at 20.degree. C. 
and a relative humidity of 90 to 95%. In the same manner cucumber plants 
in the two-leaf stage and rice plants in the four-leaf stage were infested 
with conidia of Erysiphe cichoracearum (cucumber mildew) and Piricularia 
oryzae, respectively. 3 Days after infestation, the plants were sprayed to 
the drip off with compounds of the invention in different concentrations. 
As comparative agents compounds A and B were used in the same 
concentrations. After a time of incubation of 10 to 14 days, the plants 
were examined as to their infestation with fungi. The degree of 
infestation is expressed in the following table IV in % of infested leaf 
surface, calculated on untreated and infested control plants (=100%). 
TABLE IV 
______________________________________ 
Effect against phytopathogenic fungi 
infested leaf surface in % 
when applied against 
concentration Erysiphe 
(mg of AS per 
Erysiphe cichor- 
Piricularia 
Compound of 
liter of spray 
graminis acearum 
oryzae 
Example liquor) (wheat) (cucumber) 
(rice) 
______________________________________ 
250 0 0 -- 
1 a 125 0 0 -- 
250 -- 0 -- 
2 a 
(Na-salt) 
125 -- 0 -- 
250 0-3 0 -- 
6 125 3 0 -- 
250 0-3 0 0-3 
8 a 125 3 0 3 
A 250 5 5 -- 
125 10 10 -- 
B 250 5 -- -- 
125 10 -- -- 
C 250 -- 5 -- 
125 -- 15 -- 
D 250 -- -- phytotoxic 
125 -- -- burnings 
E 250 -- -- 15 
125 -- -- 25 
untreated 
infested 100 100 100 
plants 
______________________________________ 
EXAMPLE IV (bactericidal effect) 
In Petri dishes 0.02 cc each of a bacterium suspension of Xanthomonas 
malvacearum and Corynebacterium michiganense was dropped on the center of 
a culture agar for bacteria, which culture had previously been admixed 
while still liquid with the compounds listed in Table V in different 
concentrations. The inoculated agar plates were evaluated after 4 days and 
the growth inhibition was determined in % in comparison with control 
plates (infested agar without addition of active substance (0% 
inhibition). 
TABLE V 
______________________________________ 
Bactericidal effect 
Xanthomonas Corynebacterium 
Compound of 
concentration 
malvacearum michinanense 
Example ppm (gram-negative) 
(gram-positive) 
______________________________________ 
11 a 250 97 95 
(Na-salt) 
125 70 50 
12 a 250 97 -- 
125 80 -- 
1 a 250 -- 100 
125 -- 100 
11 a 250 -- 100 
(acid) 
125 -- 100 
______________________________________