DE805523C - Process for the production of histamines - Google Patents

Description

Process for the production of histamines The previously known Syntheses for the histamine (@ -Amilioäthylimidazol) go from Schvver accessible Substances run off or run with very little yield.

It has now been found that histamine and its substitution products can be used obtained in good yield if one, 4-butanediol-one- (2) or its r, 4-substitution products with aldehydes and ammonia in the presence of milder (@ x @ dationsmittel and converted into the resulting oxethylimidazole replaced the oxy group by the amino group.

The butanediolones required as starting materials are easily accessible by hydrating fully 2-butynediol- (i, 4) and its i, 4-substitution products, in particular the r, 4-alkyl derivatives. The reaction proceeds, shown using the example of the butanediolone itself, in the sense of the following equations where R denotes hydrogen or the radical connected to the carbonyl group in the aldehyde used. The products obtained are imidazoles oxyethylated in the 4- or 5-position.

Copper (I1) salts have proven to be particularly effective as oxidizing agents, which are converted into copper (1) compounds during the implementation. You get that Imidazole in the form of its copper compound as a precipitate; in this form it leaves separate well. By decomposing the copper compound, e.g. B. with hydrogen sulfide, one obtains the free imidazole.

The reaction is expediently carried out in an aqueous medium at moderately elevated temperatures Temperature carried out. The replacement of the hydroxyl group by the amino group you can either directly by treatment with ammonia or in the usual way by converting the ß-oxyethyl compound into the ß-haloalkyl compound and reacting with ammonia.

The parts given in the example below are parts by weight.

Example In a solution of 500 parts of copper (11) sulfate in 2ooo Parts of water and 2,000 parts of 20 percent aqueous ammonia are left at 7o 8o "104 parts of 1, 4 butanediol-one (2) and zoo parts of 3% aqueous formaldehyde solution come in. The copper (I) salt of 4 (5) -ß-oxyethylimidazole is formed in the form a chocolate-brown precipitate. After another hour of heating to 7o The mixture is cooled to 85 ° and the precipitate is filtered off. One slurries put it in water and saturate it with hydrogen sulfide. After filtering off the The precipitated copper sulfide becomes the aqueous solution of the imidazole obtained in this way evaporated in vacuo and the residue distilled in vacuo (Kpi = Uo to 175 °). A yellow-colored syrupy mass is obtained which, after standing for a while, forms crystals solidified (picrat F = i44 °). Yield: 59 parts of oxyethylimidazole.

10 8 parts of the Oxyätliylimidazol are with excess hydrochloric acid added and evaporated to dryness in vacuo. The resulting chlorohydrate sets one with 300 parts of thionyl chloride hot 10 to 20 °. Excess thionyl chloride is evaporated in vacuo and the residue dissolved in 600 parts of alcohol.

The alcoholic solution of the hydrochloric acid chlorine, ithylimidazole is saturated with ammonia while cooling with ice and then placed in an autoclave for t2 hours heated to 100 °.

After the ammonium chloride which has separated out has been filtered off, the alcoholic chloride becomes The solution was evaporated in vacuo and the histamine was distilled (bp2 = 160 to 65 °). Yield: 45 parts of histamine.

Claims (1)

PATENT .aNSI'riLCH: Process for the production of histamine and its Substitution products, characterized in that 1, 4-butanediol-one (2) or its 1,4-substitution products in the presence of a mild oxidizing agent with Ammonia and an aldehyde converts and in the resulting ß-Oxyäthylimidazol the Oxy group replaced by the amino group in a known manner.