DE641598C - Process for the preparation of heterocyclic compounds - Google Patents

Description

It would be found to be new

heterocyclic compounds can be obtained if you have a-Amiiioimidazole, whose imidazole ring with 'an aromatic, heterocyclic or aromatic-heterocyclic ring system is condensed, with 1, 3-Dicarbonylverbindungen ο which converts its descendants under heating. For example, the Condensation of α-aminobenzimidazole with acetylacetone according to the following equation;

CH ₃

-NH

C • NH ₂ + CH ₃ .

in'

CO • CH ₂ • CO • CH ₃ J-CH ₃ + 2H ₂ O

the DimethylabkÖmmKng- a ring system., called the Benzirni'dpyrimidin and its Ringsystäem was numbered in the following way:

The above conversion equation shows that the three on the aminobenzimidazole grouping existing hydrogen atoms bound to nitrogen during condensation consumed for 'dehydration will. This presumably forms initially through conversion of the primary amino group Connections in the manner of the Schiff's bases, which are already in proportion condensed further directly to the compounds with the new ring system by gentle heating will. In the already known reaction between 2-aminobenzothiazole and AcetesBigester only have 2 hydrogen atoms available for condensation Disposal. Ice aoetoacetylaminobenzothiazoles are formed first, their aliphatic side chain, only at higher temperatures. Enters condensation with ring formation.

As starting materials for the present

Methods used α-aminobenzimidazole compounds of the type indicated are condensable due to the action of cyanogen bromide Orthodiamines. the aro-

*) The inventor has been indicated by the patent seeker;

Dr. Hans Henecka in Wuppertal-Elberfeld.

very easy to obtain heterocyclic or aromatic heterocyclic series; They can contain any substituents, β The condensation of the marked ^ i "a-aminobenzimidazole compounds easily and smoothly with all ι compounds, such as acetylacetone, benzoylaoeton, acetoacetic ester, malonic ester and with their alkali compounds, also with derivatives, z. B. the enol forms of the i, 3-dicarbonyl compounds, such as the oxygen alkyl derivatives of the 1,3-dicarbonylyer bonds or those derivatives of these compounds in which the oxygen atom of a carbonyl group is replaced by a double-bonded nitrogen group.

example 1

10 g of a-aminobenzimidazole are heated to the boil with 100 ecm of acetylacetone S for up to 6 hours. On cooling, colorless crystals of 2,4-Dimethylbenzimidpyrimidins separate out, melting after recrystallization from alcohol at 231-232 ^0th

If equimolecular amounts of α-aminobenzimidazole and acetylacetone are heated in an alcoholic solution, a compound with a melting point of 242 to 243 ⁰ , which is sparingly soluble in alcohol, separates out after a short time. It is a molecular compound of 1 mole of 2,4-dimethylbenzimidopyrimidine and 2 moles of a-ammobenzimidazole.

The 2,4-dimethylbenzimidopyrimidine is soluble in the usual organic solvents; it is easily soluble in dilute acids with which it forms mono-acidic salts.

Example 2

10 g of 6-nitro-a-aminobenzimidazole (obtained from 4-nitro-i, 2-phenylenediamine, and cyanogen bromide, F. 240 ⁰⁾ are heated with 100 cc of acetylacetone S to 6 hours to boiling. During the heating process, the 7-nitro-2,4-dimethylbenzimide pyrimidine separates out in light yellow, fine crystals. They are only sparingly soluble in the usual organic solvents. When heated to temperatures above 260 °, they gradually decompose, turning dark, without melting.

Example 3

10 g of 6-methoxy-a-aminobenzimidazole (obtained from 4-methoxy-i, 2-phenylenediamine and cyanogen bromide, ^{mp 202 0} ) are heated to boiling with 100 ecm of acetylacetone for 6 hours.

Fine, almost colorless crystals separate from the hot solution when it cools.

After recrystallization from benzene with the addition of a little alcohol, the 7-methoxy-2,4-dimethylbenzimidopyrimidine thus obtained melts at 197 ^° .

The 7-ethoxy-2,4-dirnethylbenzimidopyrimidine obtained in a corresponding manner from 6-ethoxy- 'a-aminobenzimidazole (mp 211 to 21 2 °) forms, after recrystallization from benzene, pale yellow, green-tinged leaflets from

F. 204 ⁰ .

Example 4 _7C

10 g of the obtained from 5,6-diaminoquinoline by the action of cyanogen bromide α-Aminoimidazolverbindung mp 265 ⁰ are heated with 100 cc of acetyl acetone for 8 hours boiling. Even in the heat, fine, white crystals separate out, which, after recrystallization from alcohol, melt at 285 to 286 ° and have the following composition:

From the group consisting of 7, 8-diaminoquinoline (F. 102 ^0; yellow needles) obtained by the action of cyanogen bromide a-Aminoimidazolverbindung mp 17 5 ⁰ is obtained in the reaction with acetylacetone in the manner described above a Chinolylimidpyrimidinverbindung, which at 245 decomposes to 250 ⁰ with a dark color and probably has the following composition:

CH ₃

Example 5

10 g of a-aminobenzimidazole are heated to 150 ° to 160 ° for 5 hours in an amount of benzoylacetone which is often the same. After cooling, it is dissolved in ether and the solution is extracted with about 3 to 50% hydrochloric acid. A light yellow-green precipitate separates out of the acidic solution with dilute sodium hydroxide solution. After recrystallization from alcohol yellow crystals is obtained from 2-methyl-4-phenylbenzimidpyrimidin, melting at 173 ^0th

If equimolecular amounts of α-aminobenzimidazole and benzoylacetone are heated in alcoholic Solution, after 3 hours of boiling a light yellow-green precipitate (mp 243 °) of the molecular compound is obtained from 1 mole of 2-methyl-4-phenylbenzimidopyrimidine and 2 moles of a-aminobenzimidazole.

Example 6

To a solution of 51 g of α-aminobenzimidazole hydrochloride in 200 ecm of alcohol, a solution of 40 g of oxyethylene acetoimodium in 700 ecm of alcohol is added dropwise at room temperature with stirring within 3 to 4 hours. After standing for 12 hours, the precipitated sodium chloride is filtered off with suction, the alcoholic solution is evaporated under reduced pressure, the crystalline residue is dissolved in dilute acetic acid and precipitated by stirring into dilute sodium hydroxide solution. The thus obtained 2-Methylbenzimidpyrimidin forms by recrystallizing twice from alcohol yellow crystals, melting at 229 ^0th

Example 7

10 g of a-aminobenzimidazo], are heated ^{to 120 to 130 0 in 75 ecm acetoacetic ester for 8 hours.} Small, glittering, white crystals soon separate from the solution that is initially formed, and these rapidly multiply during heating. After cooling, the crystal mass is filtered off with suction and washed thoroughly with alcohol. The white crystal flour thus obtained is 2-methyl-4-oxybenzimidopyrimidine. It is easily soluble in dilute sodium hydroxide solution and does not yet ^{melt when heated up to 280 °.} . .

The same connection can also be reached if, for example, instead of acetoacetic ester equal parts of ß-Ajninocrotonsäureester (or ß-Iminobuttersäureester) or ß-Äthoxycrotonsäureester applies.

Example 8

ro g of a-Ammobenzirnidazole are heated in 100 ecm malonic acid diethyl ester for 6 hours to 150 to 160 °. With vigorous boiling occurs fairly violent. Implementation with the deposition of a light brown, finely crystalline powder. After cooling, the precipitate is filtered off with suction, washed with ether, dissolved in dilute sodium hydroxide solution and reprecipitated with dilute acetic acid. The white, slightly yellowish powder obtained after suctioning off, washing out and drying is 2,4-D1-oxybenzimidopyrimidine. It does not yet melt when heated up to 280 ^°.

Claims (1)

Claim: Process for the preparation of heterocyclic Compounds, characterized in that a-Aminoimidazolei their Imidazole ring with an "aromatic, heterocyclic or aromatic-heterocyclic ring system is condensed with i, 3-dicarbonyl compounds or their Offspring condensed with heating.