DE1957259C3 - Process for the preparation of pure 4-amino- and 5-aminoindane - Google Patents

Description

Methods of making 4-amino- and 5-aminoindan are particularly desirable for recovery of the previously difficult to access 4-Aminoindans, which as an intermediate, z. B. for production of pharmaceuticals, is required.

It is known (see reports of the German Chemical Society, Vol. 60, [1927] p. 435) that one the isomer mixture of ~ 40% 4-nitroindane and ~ 60% 5-nitroindane resulting from the nitration of indane can split into the components by multiple fractional distillation and crystallization. the Pure nitroindanes can then easily be converted into the corresponding aminoindanes by reduction. The disadvantage of this process is the extremely difficult and lossy separation of the nitroindanes; 4-nitroindane, in particular, which is contained in the mixture in a smaller amount, can only be used with difficulty in this way represent.

In DE-PS 4 34 403 (Friedlander, Vol. 15,

P.341; Beilstein, 4th ed., EII, vol. 12, p.655) is described that pure aminoindan can be obtained by doing this in the nitration of indan and following reduction resulting mixture of 4- and 5-aminoindane with half an equivalent of formaldehyde reacted in hydrochloric acid solution, the 4-aminoindane preferably being converted into the N-methylene compound is, and the unchanged remainder of 5-aminoindane is distilled from alkaline solution with steam. the end 4-Aminoindan cannot be added to the residue of 4- and 5-Methylenaminoindan, or only with difficulty win pure, so that this process cannot be used for the industrial production of both isomers is.

The main patent 19 50 219 relates to a process for the production of pure 4-amino and 5-Aminoindane by reducing the isomer mixture of 4- and 5-nitroindane and separation of this reduced mixture, the isomer mixture of 4- and 5-Aminoindan dissolves in a lower alcohol, resulting in 5-Aminoindan as succinate with succinic acid precipitates and converted into the free base by treatment with alkali, while one of the Succinate precipitation, the filtrate obtained by evaporation and extraction of the residue with the 4-aminoindane non-polar solvents isolated.

In an embodiment of the method of the patent 1950 219 it has now been found that one instead of the succinic acid used for selective precipitation, also malic acid or fumaric acid can use and accordingly the 5-aminoindane precipitates as fumarate or malate, as at the beginning claimed The low price of these two acids makes the process considerably cheaper. Fumaric acid will preferably used

The reduction of the nitroindane mixture, the production and work-up 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

Accordingly, the reduction of the nitroindane mixture can after all be used for the reduction of the pure Isomeric known methods are carried out,

z. B. with acids and finely divided metals, such as iron filings, or by catalytic hydrogenation with Raney nickel or palladium as a catalyst. The latter method is preferred because it is less contaminated Products are created.

Methanol is expediently used as the solvent for malate or fumarate formation, but they are in principle other lower alcohols are also suitable.

In addition to the 4-aminoindane, the evaporation residue from the precipitation mainly contains excess acid and still residues of 5-aminoindane malate or fumarate. For the purpose of separation, therefore, all are generally non-polar Solvents can be used which dissolve the 4-aminoindan sufficiently and in which the more polar acid and the corresponding amine salt are insoluble. Proven

J5 mixtures of ether and ligroin or carbon tetrachloride and ligroin have a ratio of about 2: 1 to 1: 5.

The two acids used as auxiliary substances in the precipitation can optionally be obtained from the remainder of the Evaporation residue and from the alkaline solution that remains after the 5-aminoindane has been separated off, to be recovered.

In the following examples the further embodiments are claimed according to the invention Procedure described in more detail.

example 1

A mixture of isomers of 4-aminoindane and 5-aminoindane produced by the catalytic hydrogenation of 16.3 g of an isomer mixture consisting of 39.0% 4-nitroindane, 55.6% 5-nitroindane and 5.4% not definable by-products, is dissolved in 150 ml of methanol, 6.1 g of fumaric acid are added and the mixture is heated to 60.degree Stirred until a clear solution forms. The mixture is then kept at 0 ° C. for several hours left to stand, 5-aminoindane fumarate crystallizing out. After filtering and washing with

10 g of pure 5-aminoindane fumarate (melting point 175-178 ° C.) are obtained with cold methanol. The filtrate is with the methanolic wash filtrate combined and evaporated to dryness. The residue obtained in this way is with 100 ml of a mixture of ether and L.igroin (1: 1)

hi well stirred, allowed to stand for a short time at 0 ⁰ C and filtered. The residue is washed with an ether / ligroin mixture (1: 1). The combined ether / ligroin filtrates are then concentrated and kept at 0 ° C. for some time

left to stand and filtered. The small amount of deposited crystals is in turn with ether / ligroin (1: 1) washed, whereupon all ether / ligroin filtrates combined and evaporated to dryness will. The residue obtained is 4.5 g of isomerically pure 4-aminoindane in 86% yield; the melting point is -5 to -3 ° C and corresponds to the values given in the literature.

To convert the 5-aminoindane fumarate into the free base, proceed as follows:

10 g of crude 5-aminoindan fumarate are dissolved in 75 ml of concentrated soda solution and 30 ml of chloroform '/ 2 Stirred for one hour; it is then filtered and the chloroform phase is separated off in a separating funnel. the aqueous phase is extracted again with chloroform. Finally, the combined are Chloroform phases dried over sodium sulfate and evaporated to dryness. 5-amine indane is obtained 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.

Example 2

A according to Example 1 produced a mixture of isomers of 4-aminoindan and 5-aminoindan is dissolved in 150 ml of methanol with 7.1 g of malic acid were added and as long stirred at 6O ⁰ C until a clear solution forms Subsequently, the 5-aminoindan-malate ( Mp. 130-132 ⁰ C), as described in Example 1, crystallized, filtered off and purified by washing with cold methanol. The combined filtrates are evaporated and worked up according to Example 1, but using a mixture of ether / carbon tetrachloride 1: 1. 4.5 g of 4-aminoindane are obtained in 86% yield; Mp. -5 to -3 ° C.

The conversion of the 5-aminoindan malate into the free base is carried out in the manner described in Example 1 Way.

Claims (1)

Claim: Process for the preparation of pure 4-amino- and 5-arainoindan by reducing the at Nitration of isomeric mixture of 4- and 5-nitroind ui obtained from indane and separation of this reduced mixture, using the method of patent 19 50 219 the isomer mixture from 4- and 5-Aminoindan dissolves in a lower alcohol, from it with succinic acid that 5-Aminoindane precipitates as succinate and converted into the free base by treatment with alkali, while from the filtrate obtained in the precipitation, the 4-aminoindane by evaporation and Extracting the residue with non-polar solvents, characterized in that, that instead of succinic acid, fumaric acid or malic acid is used and 5-aminoindane as fumarate or maiat precipitates.