DE1957259A1 - Process for propg 4-and 5-aminoindanes from - isomeric mixtures - Google Patents

Abstract

In Ger. Pat. appl. 1950219, pure 4- and 5-aminoindanes are prped from an isomeric mixture obtd by hydrogenation of the isomeric mixture of the 4- and 5-nitroindanes by dissolving the mixture in a lower alcohol adding succinic acid whereby the 5-isomer is pptd. as the succinate and converted to the free bas by treatment with alkali. The 4-isomer remaining in the soln is then obtd. as the succinate by evaporating the soln. and liberating the free base with alkali after extracting the evaporation residue with a non-polar solvent. In the present invention the succinic acid is replaced by the cheaper malic and esp. fumaric acid.

Description

Process for the production of pure 4-amino- and 5-aminoindane additive for patent application P 19 50 219.3 is the subject of patent application P 19 50 219.3 a process for the production of 4-amino- and 5-aminoindane, in particular for its extraction of 4-aminoindane, which was previously difficult to access; which as an intermediate, e.g. for the production of pharmaceuticals, is required.

It is known [cf. Chem. Ber. 60, 435 (1927)] that the Nitration of indane isomer mixture of -40 1J 4-nitroindane and%% 5-nitroindane by multiple fractional distillation and crystallization in can split the components.

The pure nitroindanes can then easily be converted into the corresponding ones by reduction Aminoindane are converted. The disadvantage of this method is that it is extraordinary difficult and lossy separation of the nitroindanes; especially 4-nitroindane, which is contained in the mixture in a smaller amount, can only be represented poorly in this way.

Following the procedure of the main application P 19 50 219: 3 one obtains on simple way and in good yields of pure 4- and 5-atninoindanes, if you can during the nitration of indane resulting mixture is reduced, and the aminoindanes obtained treated with succinic acid. Surprisingly, only 5-aminoindane is formed a sparingly soluble, crystalline succinate, while the 4-aminoindane remains in solution.

In an embodiment of the method of patent application P 19 50 219.3 it has now been found that instead of the succinic acid used for selective precipitation Also use malic acid and above all bunaric acid, their low price the procedure is considerably cheaper.

The reduction of the nitroindane mixture, the production and processing of the salts, as well as the recovery of the acids used for salt formation carried out according to the procedure described in the main application.

In the following examples are. the other embodiments of the described in more detail in the parent application claimed process.

Example 1 A mixture of isomers of 4-aminoindane and 5-aminoindane, produced by catalytic hydrogenation of 16.3 g of a mixture of isomers, consisting of -from 39.0% 4-nitroindane, 55.6% 5-nitroindane and 5.4% non-definable by-products, is dissolved in 150 ml of methanol, mixed with 6; i g of fumaric acid and kept at 60 ° C stirred until a clear solution forms. The mixture then becomes several Left to stand for hours at OOC, 5-aminoindane fumarate crystallizing out.

After filtering off and washing with cold methanol, one obtains 10 g of pure 5-aminoindane fumarate (m.p. 175-178 ° C). The filtrate is with the methanolic Wash filtrate combined and evaporated to dryness. The residue thus obtained is stirred well with 100 ml of a mixture of ether and ligroin (1: 1), short Left to stand for time at 0 ° C. and filtered off. The residue is mixed with ether / ligroin (1: 1) washed. The combined ether / ligroin filtrates are then concentrated and left to stand for some time at OOC and filtered.

The small amount of separated crystals is again mixed with ether / Ligroin (1: 1) washed, whereupon all ether / ligroin filtrates are combined and used for Dry to be evaporated. 4.5 g of isomerically pure 4-aminoindane are obtained as residue in 86% yield; the melting point is -5 to -3 ° C and corresponds to that in values given in the literature.

To convert the 5-aminoindan fumarate into the free base, one proceeds as follows before 10 g of rones 5-aminoindan fumarate are in 75 ml of concentrated soda solution and 30 ml of chloroform stirred for 1/2 hour; it is then filtered and the chloroform phase separated in the separating funnel.

the aqueous phase is extracted once more with chloroform.

Finally, the combined chloroform phases are dried over sodium sulfate dried and evaporated to dryness. MEn receives 5-aminoindane as a pale yellow-brown, chromatographically pure oil which crystallizes out on standing (5.3 g). To Recrystallization from ligroin melts the compound at 33-34 ° C.

B e i s p i e 1 2 A mixture of isomers prepared according to Example 1 of 4-aminoindan and 5-aminoindan is dissolved in 150 ml of methanol with 7.1 g of malic acid added and stirred at 600C until a clear solution forms. Afterward the 5-aminoindan malate (melting point 130-132 °) is crystallized out as described in Example 1, filtered off and purified by washing with cold methanol. The combined filtrates are evaporated and according to Example 1, but using a mixture worked up by ether / carbon tetrachloride 1: 1. 4.5 g of 4-aminoindar are obtained in 80 5% yield; M.p. -5 to -30C.

The conversion of the 5-Aminoidan-malats in the free base takes place in the manner described in Example 1.

Claims (1)

P a t e n t a n s p r u c h Process for the preparation of pure 4-amino- and 5-aminoindan according to the method of patent application P 19 50 219.3, in which a mixture of 4- and 5-Aminoindan dissolves in a lower alcohol, with Bernateinsäure the 5-Aminoindan precipitates as succinate and converted into the free base by treatment with alkali, whereupon the 4-aminoindane is obtained from the filtrate obtained in the precipitation by evaporation and extracting the residue with non-polar solvents isoiterj, thereby characterized in that fumaric acid or malic acid is used instead of the stinic acid and the 5-aminoindane precipitates as fumarate or malate.