CS240932B1 - Preparation method of 1,2:3,4:5,6-tri-isopropylidenmannitol - Google Patents

Abstract

The aim of the solution is to increase the yield 1,2: 3,4: 5,6-tri-O-isopropylidene-mannitol in the reaction of mannitol with acetone sulfuric acid catalysis. This purpose is achieved by the fact that the mixture is cooled to From 0 ° C to -60 ° C and leave at this temperature 10 h to 170 h. Chemical equilibrium with reduction temperature shifts in favor of the above said substances.

Description

The invention relates to a process for the preparation of 1,2: 3,4: 5,6-tri-O-isopropylidene-mannitol.

The synthesis of rnannitol with acetone under catalysis of conc. sulfuric acid with a yield of 75% of theory (Wiggins LF: J. Chem. Soc. 1946, 13) · In a series of experiments to reproduce this process (raw materials: D-mannitol with less than 0.1% water; acetone dried with calcium chloride content However, yields ranged around 55% of theory on average (see also, for example, the description of the invention for the auto-enlightenment 194386, in which the authors give a yield of 54%) ·

A study of the reaction mixture composition versus time and temperature was conducted. Gas chromatography analysis showed that

a) Reaction of rnannitol with acetone according to Wiggins produces a mixture of five

O-isopropylidene derivatives of mannannitol (1,2. * 3,4: 5,6-tri-O-,

1,2: 3,4-di-O-, 1,2: 5,6-di-O-, 1,2-O- and 3,4-O-isopropylidene-mannitol)

b) this mixture with increasing reaction time leading to chemical equilibrium

c) at a reaction temperature of 23 ° C and a reaction time of 6.75 hours at which complete dissolution of rnannitol occurred, the conversion of rnannitol to 1,2: 3,4: 5,6-tri-O-isopropylidene-annitol was 67%; it dropped to 64% at 79h and remained at this value for 384h.

From this it is clear that by extending the reaction time nothing is gained, quite the contrary.

(d) the equilibrium composition of the reaction mixture appears to be highly temperature dependent. The results are given in the order of temperature, time of leaving the reaction mixture at this temperature, conversion of mannitol to 1.2: 3.4:

5,6-tri-O-isopropylidene-mannitol: 45 ° C, 6h, 54%; 23 ° C, 384h, 64% and 5 ° C, 169h, 70%; -22 ° C, 169h, 84%. -22®C occurs

240 932

- 2 to favorably influence the chemical equilibrium due to the elimination of crystalline 1,2: 3,4: 5,6-tri-O-isopropylidenemannitol from the solution.

It is an object of the present invention to utilize the dependence of the equilibrium composition of the reaction mixture on temperature.

The process according to the invention consists in reacting mannitol with acetone according to Wiggins, preferably at room temperature, and after dissolving mannitol, the reaction mixture is cooled and left at a reduced temperature until a chemical equilibrium is established or reacted to it. the system zooms in sufficiently. The most suitable temperature is below -20 ° C, with a reaction time of several days. Thereafter, the reaction mixture is diluted with water or an aqueous solution of a neutralizing agent (e.g. an alkali carbonate) and the precipitated 1,2: 3,4: 5,6-tri-O-isopropylidene-mannitol is filtered off with suction or recrystallized. A further fraction is obtained from the mother liquors after concentration.

The product obtained according to the invention has a sharper and higher melting point than the product obtained previously according to the Yiggins method after the first isolation, the yield increased from 55% to 78%.

The invention is explained in more detail in the following example.

Example

To a suspension of 8.00 g of D-mannitol in 100 ml of acetone (dried with calcium chloride) was added with stirring 0.8 ml of 98% sulfuric acid, and the mixture was stirred at room temperature. at 4 h at which time mannitol was completely dissolved. Slight turbidity was removed by filtration and the mixture was left at -45-5 ° C for 95 h. Then it was diluted with a solution of 2.11 g of sodium carbonate in 100 ml of water and allowed to crystallize. After suctioning off the crystals, washing with 20 ml of water and drying, 10.66 g of the substance having a melting point of 69-70 [deg.] C., which contained 9.96% of salt, were obtained. Dissolution in acetone, suction of the undissolved salt and evaporation of the solvent gave 9.60 g of product (72.3%), mp 69-70 ° C; gives for the L-isomer mp 69-70 ° C, [α] _D -12.6 ° (c 11, ethanol) / Baer E., Fischer H.

L. L. J. Amer. Chem. Soc. 61, 761, 764 (1939). The mother liquors from the reaction mixture were concentrated under reduced pressure to about half the volume. The precipitate was filtered off with suction, washed with 15 ml of water

Μ 3 ^M

240 932 and dried. An additional 0.74 g (5.6%) of the product with m.p. 67-69 ° C, + 12.8 ° (c 4, ethanol). The total yield was

10.34 g (77.8%).

The invention can be used in the synthesis of 2,3-O-isopropylidene-D-threitol (see ref. No. 194386), which is a starting material for the synthesis of phosphine ligands whose transition metal complexes of the periodic group, in particular rhodium. , serves as homogeneous catalysts for asymmetric syntheses (Caplar V, Comisso G., Sunjic V .: Synthesis 1981, 85) ·

Claims (1)

SUBJECT OF THE INVENTION A process for the preparation of 1,2: 3,4: 5,6-tri-O-isopropylidene-mannitol by the reaction of mannitol with acetone under sulfuric acid catalysis, characterized in that the reaction mixture is left at 0 ° C to -60 for 10 to 170 hours before isolating the product. ° C, preferably at -25 ° C.