SE415970B - NEW PROCEDURE FOR THE PREPARATION OF N- (TRANS-4-HYDROXICYCLOHEXYL) - (2-AMINO-3,5-DIBROMO-BENZYL) -AMINE - Google Patents

Description

730548912 the compound N- (trans-4-Hydroxy-cyclohexyl) - (2-amino-3,5-dibromobenzyl) -amine and its acid addition salt.

However, this compound can be prepared only in moderate yield according to the procedures described in the above-mentioned German disclosure document. They are obtained according to Example 1 of this disclosure document by bromination of the corresponding halogen-free compound only in a yield of 36% of the theoretical value. It has surprisingly been found that the above compound in a yield of over 90% of the theoretical value and with excellent purity can be prepared by 2-amino-3,5-dibromobenzaldehyde, in the presence of a catalytic amount of an acid , is reacted with trans-4-amino-cyclohexanol to give N- (2-amino-3,5-dibromobenzylidene) -trans-4-aminocyclohexanol of the general formula 'Br Q CH == N ÜH .- (II) Br which in a solvent, at temperatures up to the boiling temperature of the solvent used is reduced with a complex metal hydride.

The reduction takes place with catalytically activated hydrogen, for example with hydrogen in the presence of Raney nickel or cobalt as catalyst, with hydrogen 1 atomic state, e.g. with activated, metallic aluminum, with sodium amalgam and ethanol or with zinc and hydrochloric acid, or particularly advantageously with a complex metal hydride such as lithium aluminum hydride or sodium borohydride in a suitable solvent such as ethanol, ethanol / water, tetrahydrofuran, dioxane, dioxane / water or ether and at temperatures above the boiling temperature of the solvent used. The free bases which may be obtained can, if desired, preferably without prior isolation, be transferred with a physiologically acceptable inorganic or organic acid into an acid addition salt.

The new starting compound of the general formula II is obtained in high yields by reacting the 2-amino-3,5-dibromobenzaldehyde known from the literature with trans-4-amino-cyclohexanol.

The reaction preferably takes place in a solvent such as ethanol or benzene, preferably in the presence of a catalytic amount of an acid, e.g. p-toluenesulfonic acid and at temperatures up to the boiling temperature of the solvent used, the reaction is particularly advantageously carried out in a water separation device. The invention is further illustrated by the following examples, in which the temperatures refer to degrees Celsius.

Example A N- (2-amino-3,5-dibromobenzylidene) -trans-4-amino-cyclohexanol 500 g of trans-4-amino-cyclohexanol hydrochloride were added with a solution of 190 g of potassium hydroxide in 4 l of absolute ethanol. , was heated with stirring to boiling and cooled again to room temperature. The precipitated potassium chloride was filtered off with suction, the filtrate was added with 893 g of 4-amino-3,5-dibromobenzenedehyde and refluxed with stirring; after about 20 minutes the aldehyde was completely dissolved. The reaction solution was evaporated after boiling for 4 hours in a water-jet vacuum, the residue was taken up in 1.8 l of hot benzene, filtered off from insoluble precipitate, and the filtrate was allowed to stand at + 5 ° for crystallization. The yellow precipitate was filtered off with suction. and 200 ml of cyclohexane and dried in air. Melting point 124-125.5 ° C.

Example 1 N- (trans-4-hydroxy-cyclohexyl) - (2-amino-3,5-dibromobenzyl) -amine hydrochloride 1,000 g of N- (2-amino-3,5-dibromobenzylidene) -trans- 4-Amino-cyclohexanol was added with 6 l of absolute ethanol and 100 g of sodium borohydride and stirred for 8 hours. After about 2 hours, everything was resolved. The reaction temperature rose slowly within 3 hours from 14 ° to 290, remained at this temperature for 3 hours and then slowly dropped again. The reaction solution was allowed to stand overnight, and then an excess of sodium borohydride with 0.8 l of concentrated hydrochloric acid was carefully added. There was precipitated N- (trans-4-hydroxy-cyclohexyl) - (2-amino-3,5-dibromobenzyl) -amine hydrochloride. The mixture was diluted with 12 L of water, added alkaline with 0.8 L of concentrated ammonia and extracted twice with about 3.1 chloroform. The organic phase was added with activated carbon and sodium sulfate, filtered and evaporated in a water jet vacuum. The residue was dissolved in 1.8 l of hot absolute ethanol, filtered and charged with absolute ethanolic hydrochloric acid. This crystallized out of N- (trans-4-hydroxy-cyclohexyl) - (2-amino-5,5-dibromo-benzyl) -amine hydrochloride, which was filtered off with suction after standing for 20 hours, washed with absorbent. vv .... ._. ~ .- "~ '-"' '".l 7305489-2 in lye ethanol and acetone and then dried.

Yield: 1 003 g (91% of theory).

Melting point of the hydrochloride: 233 - 2340 (decomposition) In the same way, other acid addition salts with physiologically acceptable inorganic or organic acids can be prepared.

Claims (2)

'73051489-2 PATENTK RAV 1. A process for the preparation of N- (trans-4-hydroxy-cyclohexyl) - (2-amino-3,5-dibromobenzyl) -amine and its acid addition salts, characterized in that 2-amino-3 , 5-dibromobenzaldehyde in the presence of a catalytic amount of an acid is reacted with trans-4-amino-cyclohexanol and the formed N- (2-amino-3,5-dibromobenzylidene-trans-4-aminocyclohexanol in a solvent, at temperatures up to the boiling temperature of the solvent used, it is reduced with a complex metal hydride and the base obtained, if desired, is transferred into its physiologically tolerable salt with an inorganic or organic acid. 2. A process according to claim 1, characterized in that lithium aluminum hydride or sodium borohydride is used as the complex metal hydride. MENTIONED PUBLICATIONS: