DE1300111B - Process for the preparation of optically active cyanohydrins - Google Patents

Description

The invention relates to a method for the production of optically active ones Cyanohydrins by reacting aldehydes with hydrocyanic acid in the presence of highly active asymmetric oxynitrilase.

The discovery of oxynitrilase in 1908 was an incentive to use this enzyme, which can be obtained from vegetable raw materials, for the production of cyanohydrins. Experiments which extended exclusively to mandelonitrile yielded dark brown colored oils of undefined purity with very little specific rotation. A certain improvement of the process was achieved only after the purification of the enzyme was succeeded (W. B ec k it, thesis, Marburg 1964).

In the first attempts with the pure enzyme, however, the optical ones were The purity of the reaction products and the yields are unsatisfactory. Besides, it was because of that during the reaction and the immediately following work-up of the products taking place irreversible damage to the relatively unstable catalyst for every new turnover requires the use of fresh enzyme.

The object of the present invention is to provide a method for representation of optically active cyanohydrins of high optical purity, which without great effort can be carried out and gives high yields and where the Catalyst can be used repeatedly.

According to the invention, this object is achieved by using the oxynitrilase in the form of their connection with an organic ion exchanger which is insoluble in the reaction mixture begins.

The inventive method offers the advantage that the oxynitrilase, which is attached to the inactive carrier material, is stable over time and at the reaction is not destroyed. It can be repeated without any noticeable reduction in activity can be used. The use of milligram amounts of the enzyme is permitted the production of optically active cyanohydrins on a kilogram scale. That on the carrier The enzyme present can in heterogeneous catalysis at room temperature the substrates implement without contaminating them. This makes working up the reaction products much easier.

Another major advantage of the method according to the invention is that the cyanohydrins are obtained in high optical purity and that the yields are very high. There is also a major advantage of the present invention Invention is that its applicability in terms of the type of to be implemented Aldehyde is not subject to any restrictions; it can be aliphatic, aromatic and heteroeyclische aldehydes are implemented.

It is particularly advantageous to use ECTEOLA cellulose as an ion exchanger (Reaction product of epichlorohydrin, triethanolamine and sodium cellulose) or DEAE cellulose (diethylaminoethyl cellulose) should be used.

The process according to the invention can be carried out in a flow-through process. It can also be carried out continuously in the customary manner.

The invention is explained in more detail below using exemplary embodiments.

Example 1 In water pre-swollen, loaded with chloride ions ECTEOLA cellulose is slurried in a column and charged with about 1 to 100 mg oxynitrilase in solution. The catalyst zone is formed in the upper part of the column. A mixture of 8.2 ml (8.5 g = 0.08 mol) of benzaldehyde in 100 ml of 0.05 molar 50 percent alcoholic acetate buffer of pH 5.4 and 3.85 ml (2.7 g = 0.1 mol) of anhydrous hydrocyanic acid in 100 ml of the same solvent are passed through the column. The optically active cyanohydrin can be extracted on loading known manner from the aqueous-alcoholic phase. After drying and evaporation of the extractant in vacuo, 10.3 g of a clear, slightly yellow-colored oil remain, which solidify in the refrigerator to form almost colorless crystals which melt at 23 ° C. In chloroform, the dextrorotatory mandelonitrile shows a specific rotation HD of +39 ° C (lit .: +48.71 C for optically pure product). The total yield, based on the benzaldehyde used, is 97 % of theory; The product contains about 90 1% right-handed and 10 1 / o left-handed mandelonitrile. Example 2 On a catalyst column prepared according to Example 1 , 6.6 ml (5.6 g = 0.08 mol) of crotonaldehyde in 100 ml of 0.05 molar aqueous acetate buffer of pH 5.4 and 3.85 ml of anhydrous hydrocyanic acid in 100 ml of the same buffer converted to optically active crotonaldehyde cyanohydrin. 5.8 g of a clear, slightly yellow-colored oil of the specific rotation [IXID = -23.51 ° C. (in chloroform) can be isolated from the aqueous phase. The yield, based on the crotonaldehyde used, is 75 % of theory. EXAMPLE 3 5.7 ml (4.65 g = 0.08 mol) of propionaldehyde and 3.85 ml of anhydrous hydrocyanic acid, dissolved in 200 ml of the buffer according to Example 2, yield 3.1 after running through the catalyst column prepared according to Example 1 and isolation from the buffer phase g of a pale yellow oil of specific rotation [IXID + 140 C (in chloroform). The yield is 45% of theory. Example 4 7.4 ml (8.95 g = 0.08 mol) of thiophene-2-aldehyde and 3.85 ml of anhydrous hydrocyanic acid in 200 ml of the buffer according to Example 1 yield 9.6 g of optically active thiophene after passing through the catalyst acid prepared according to Example 1 -2-aldehyde anhydrin of specific rotation ICCID = + 27.2 'C (in chloroform). The yield is 86.5% of theory.

Claims (2)

1. A process for the preparation of optically active cyanohydrins by reacting aldehydes with hydrocyanic acid in the presence of highly active, asymmetry render oxynitrilase, d a d u rch g e -kennz eichnet in that the Oxynitrüase in the form of their connection ion exchanger with an insoluble in the reaction mixture organic begins. 2. The method according to claim 1, characterized in that it is carried out as a flow process.