DE2035905A1 - Imidazole compounds and their manufacturing process - Google Patents

Description

203590S

CHEMICAL FACTORY STOCKHAUSEN & CIE. KREFELD

Chemical factory Stockhausen & Cie. 415 Krefeld P.O. Box 570

"Imidazole compounds and their manufacturing process"

PATENT DEPARTMENT

Your reference Your message from our reference T-telephone extension date

Kl / Da 338- 459 July 6, 1970

1,2-disubstituted 5-nitro-imidazoles show both bactericidal and fungicidal effects (Niederl.P. 6 503 442 (1965) 5 Science 162 , 1146 (1968); Ind.PP 74 212 and 72 522; DP (DDR) 42 882).

The preparation of the corresponding derivatives is therefore of interest on the one hand, but on the other hand encounters considerable preparative difficulties: the known syntheses for preparation Such nitroimidazole derivatives are time-consuming and usually run with moderate yields.

In the German Offenlegungsschrift 1 470 079 are now l-Alkyl-2- (ß-aryl-vinyl) -5-nitroimidazoles described, which from | the condensation of 1-alkyl-2-raethyl-5- »itro-imidazole with aromatic aldehydes in the presence of an alkaline condensing agent. Since the procedure described because of the severe reaction conditions resinification and decomposition of the Causes reaction partner, the number of aromatic aldehydes is limited to benzaldehyde, furfural, halobenzaldehyde and methylbenzaldehyde.

This creates connections that are completely in water insoluble or, if a hydroxyalkyl group is present in the! -position, are only extremely minimally soluble. When converting aromatic aldehydes with hydrophilic substituents such as hydroxyl and Amino groups, on the other hand, do not condense. Acid functions would intercept the basic reaction catalyst

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CHEMICAL FACTORY STOCKHAÜSEN & CIE. - 2 - KREFELD, July 16, 1970 sheet

Imidazole compounds and their manufacturing process

and make implementation impossible from this side.

It has now been found that compounds with better water solubility are obtained if! -Substituted 2-methyl-5-nitro-imidazole is reacted with heterocyclic five- and six-membered aromatic aldehydes, with nitrogen being used as Ring heteroatom the strongest hydrophilicity is achieved. Isocyclic ^ aromatic aldehydes are also reactants suitable, provided they carry at least one substituent which has a hydrophilic function or can be converted into one.

The course of the reaction can be shown by the following form

K-tert-butoxide

where mean:

R ₁ aliphatic, iso-raid heterocycloaliphatic, araliphatic, iso- and feeteroeyelic aromatic radical

R ₄ m isocyclic aromatic radical With at least one sub-2

substituent, which is converted into a hydrophil® function become »can or heterocyclic®:! · aromatic Heat © tea / with the same type of substituent »

The invention is illustrated in more detail by the naeltf®lg "d" ii example, but does not experience any limitation.

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CHEMICAL FACTORY STOCKHAUSEN & CIE. -3- KREFELD, July 16, 1970 -J * rtt.

Imidazo! Compounds and their production method

Example 1;

1- (1-methyl-5-nitro-2-imidazolyl) -2- (3-methoxyphenyl) -ethylent It will

2.35 g of 1,2-dimethyl-5-nitro-imidazole, 5j 50 g of potassium 1-tert.-butylate and

2.28 g of 3-methoxy-benzaldehyde in 30 ml of abs. Dissolved ethanol and stirred for 7 hours at room temperature. The yellow precipitate is then filtered off and recrystallized from methanol. After drying, 1.0 g of 1- (1-methyl-5-nitro-2-imidazolyl) -2- (3- «ethoxyphenyl) -ethylene with a melting point of 155.degree. C. are obtained received (23, O # d.TlW),

Example 2:

1- (l-Methyl-5-nitro-2-inidazblyl) -2- (4-cyano-phenyl) -ethylene: 2.35 g of 1,2-dinethyl-5-nitro-ifflidazole and 5 »50 g of potassium tert-butoxide are added together 2.19 g of p-cyanobenzaldehyde in 30 ml of abs. Dissolved ethanol and stirred for 7 hours at room temperature. The yellow precipitate is then filtered off with suction and washed with water. There are 3 «2g 1- (1-methyl-5-nitro-2-inidazolyl) -2- (4-cyano-phenyl) -ethylene nit obtained a melting point of 291 ° C (75 «5 # of theory).

Example 3ι

1- (1-methyl-5-nitro-2-inidazolyl) -2- (2 ^ thienyl) -8thylene.

2.35 g of 1,2-dinethyl-5-nitro-> inidazole, 5.50 g of potassium tert-butoxide and

1.90 g of 2-fomyl-thiophene (thiophene-2-aldehyde) are in 30 nl abs. Dissolved ethanol and stirred for 7 hours at room temperature. The mixture is then cooled to 0 °, the precipitate is filtered off and washed with water. 2.5 g are obtained 1- (1- methyl-5-nitro-2-inidazolyl) -2- (2-thienyl) -ethylene nit a melting point of 196 ° C (63.7 Ji of theory).

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CHEMICAL FACTORY STOCKHAUSEN & CIE. KREI = ELD, July 16, 1970 Β '"«

«* If-- Imidasolverbindungen rand their

production method

Example kl

1- (1 -Methyl - ^ - nitro - ^ - imidazoly-1) «2- (2-pyridyl) ethylene. There are 30 ml of abs. With ethanol one after the other 2.35 g of 1,2-dimethyl-5- »itro-iniidazole, 5.00 g of potassium tert-butoxide and

1.80 g of picoline aldehyde added «

After stirring for 7 hours, the mixture is cooled to 0 and the gray-green precipitate is filtered off. For cleaning, the mass is in methanol dissolved and again precipitated with water. 1.0 g is obtained 1- (1-methyl-5-nitro-2-imidazolyl) -2- (2- pyridyl) -ethylene. with a melting point of 210-212 ° C (25.9% of theory).

Example 5;

3.00 g of l- (l-methyl-5-nitro-2-imidazolyl-2- (4-cyano-phenyl) -ethylene are mixed with 3 »5 ml of concentrated sulfuric acid, to which 2.1 ml of water have been added, 30 Heated to boiling minutes, then cooled and poured into water. The precipitate is filtered off, dried and extracted with hot dioxane. The residue consists of practically pure 1- (1-methyl-5-nitro-S1-imidazolyl) -2- (4 -carboxy-phenyl) -ethylene with a melting point of 308-309 ⁰ C (yield 97% of theory).

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Claims (2)

CHEMISCHE PABRIK STOGKHAUSEN & CIE, - 5 - KREFELD, July 16, I97O bU Patents claims 1) Hydrophilic 1,2-disubstituted 5-nitro-imidazole der general. formula wherein R ₁ means! aliphatic, iso- and heterocycloaliphatic, araiiphatic, iso- and heterocyclic aromatic radical, characterized in that R_ is an isocyclischeii aroniati see remainder with water-solubilizing substances or a heterocyclic aromatic radical with or without water-soluble represents making substituents. 2) Process for the preparation of compounds according to claim i, characterized in that i-substituted 2-methyl-5- »itro-imidazo.l with an aldehyde which carries at least one substituent which can be transformed into a hydrophilic form, in a strongly basic reaction medium to react en an ± i _{2 is converted} into a water-solubilizing function. and then the substituent or substituents on R "in one 109886/1820