DD217224A1 - PROCESS FOR THE PREPARATION OF S-GLUCOSIDES - Google Patents

Abstract

The invention relates to a process for the preparation of S-glucosides. The aim of the invention is to develop a process for the preparation of 6- (b-D-glucopyranosylthio) -4-aryl-2-methylthio-pyridine-3-carbonitriles. These S-glucosides of general formula III, in which R is an optionally alkyl-, halogen- or alkoxy-substituted phenyl radical, can be obtained by reacting the pyridinecarbonitriles of general formula I in which R has the above meaning, with 2,3,4, 6-Tetra-O-acetyl-bD-glucopyranosylmercaptan in the presence of alkalis to the acetylated S-glucosides of general formula II in which R is as defined above and their deacetylation is carried out. These S-glucosides can be used as organic intermediates for further syntheses. They are particularly suitable for the synthesis of condensed heterocycles bearing a Glucopyranosylthiorest.

Description

Process for the preparation of S-glucosides Field of application of the invention

The invention relates to a process for the preparation of 6- (β-D-glucopyranosylthio) -4-aryl-2-methylthio-pyridine-3-carbonitriles.

These S-glucosides can be used as organic intermediates for further syntheses. They are particularly suitable for the synthesis of condensed heterocycles bearing a glucopyranosylthio radical.

Characteristic of the known technical solutions

6- (.beta.-D-glucopyranosylthio) -4-aryl-2-methylthio-pyridine-3-carbonitriles are not yet known.

Object of the invention

The aim of the invention is to provide a process for the production. of 6- (β-D-glucopyranosylthio) -4-aryl-2-methylthio-pyridine-3-carbonitriles.

Explanation of the essence of the invention

The S-glucosides of general formula III in which R is an optionally alkyl-, halogen- or alkoxy-substituted phenyl radical can be prepared by reacting the pyridinecarbonitriles of general formula I in which R has the above meaning,

with 2,2,4,6-tetra-O-acetyl-.beta.-D-glucopyranosylmercaptan in

presently from alkalis to the acetylated S-glucosides of general formula II in which E is as defined above and their Bntacetylierung be prepared.

The reactions of the iyridinecarbonitriles I with the acetylated glucopyranosyl mercaptan to give the acetylated S-glucosides II are carried out in an organic solvent, preferably in dimethylformamide, in the presence of alkalis, preferably potassium carbonate, with stirring. The reaction temperatures are 20-6O ⁰ C, the reaction times range in AtSaängigkeit of the reaction temperatures used from 2 to 12 hours,

Working up the reaction mixtures is carried out by addition of water and acidification with dilute mineral acid, the precipitates are filtered off, washed with water and organic solvents from recrystallized · The Bntacetylierung the acetylated S-Glucoside II is carried out in absolute methanol in the presence of sodium methanolate in Semperaturen 20 ⁰ O ₀ The duration of this Sntacetylierung is 8 to 10 hours. Some of the S-glucosides III precipitate out of the reaction mixture in crystalline form. After filtering off the precipitate and washing with absolute methanol, the mother liquor is treated until neutralization with the activated ion exchanger KPS-2CX) and then concentrated to dryness in vacuo. The residue is recrystallised from methanol.

Implementing Objects'

t- (2,3-j, 4,6-tetra-a-acetyl-.beta.-D-glucopyranosylthio) -2-methylthioiodo-phenyl-pyridine ~ 3-c arbonitrile

0.01 moles of 6-bromo-2-methylthio-4-phenyl-pyridine-3-carbonitrile and 0.01 moles of 2,3,4,6-tetra-0-acetyl-β-D-glucopyranosylmercaptan dissolved in 50 ml of dimethylformamide · After the addition of 2 g of dry potassium carbonate is stirred for 5 hours at 5O ⁰ C The reaction mixture is cooled to 20 ° 0, added with stirring with 100 ml of water and then acidified with dilute hydrochloric acid. The deposited precipitate is filtered off, washed thoroughly with water and crystallized from methanol / acetone.

Yield: 80% of theory M.p. 210-212 ⁰ C

C ₂₇ H ₂₈ N ₂ O ₉ S ₂ (588,6) Ber. C 55.09 H 4.79 N 4.76

Gef. C 55, i1 H 4.71 N 4.80

Embodiment 2

6- (2,3,4,6-tetra-O-acetyl-.beta.-D> -glucopyranosylthio) -4- (p-meth-O3qsr-phenyl) -2-methylthio-pyridine-3-carbo-nitrile 0, 01 raol is 6-bromo-4- (p-methoxyphenyl) -2-ethylthio-pyridine-3-carbonitrile and 0.01 mol is 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosylmercaptan implemented as described in Example 1 ".

Yield: 8% of theory Schrap. 203-205 ⁰ C

C ₂₈ H ₅₀ K ₂ O ₀ ^ S ₂ (618.7) Calcd. C 52.41 H 4.40 N 4.53

üef. C 52.38 H 4.44 N 4.52

Embodiment 3

6- (2,3,4,6-tetra-O-aoetyl-.beta.-D-glucopyranosylthio) -4- (p -chlorophenyl) -2-methylthio-pyridine-3-carbonitrile .01mol 6-bromo-4 - (p-chloro-phenyl) -2-methylthio-pyridine-3-carbonitrile and 0.01 mol of 2,3 »4,6-tetra-O-acetyl-ß-D-glucopyranosylrnercaptan are reacted as described in Example 1 ,

Yield: 33 $ d.Th. From 20O ⁰ C Zers.

C ₂₇ H ₂₇ ClN ₂ O ₉ S ₂ (623.1) Ber. N 4,49

Gef. N 4,83

Embodiment 4

6- (beta-D-Glucopyranosylthio) -2-inethylthio-4-phenyl-pyridine-3-carbonitrile

A mixture of 3 ml of a solution of sodium methoxide in methanol (prepared from 0.5 g of sodium and 100 ml of absolute methanol), 10 ml of absolute methanol and 0.002 mol of 6- (2,3,4, o-tetra-O) is stirred. acetyl-ß-D-glucopyraT iosylthio) -2-methylthio-4-phenyl-pyridine-3-carbonitrile 8 hours at 2O ⁰ ii C. The crystalline precipitate is filtered and washed with a little methanol

washed.

The filtrate is shaken until neutralization with activated ion exchanger (KPS-200) and then concentrated i.Vak. sur dry one. The residue is recrystallised from methanol. "The combined precipitates are recrystallized from methanol for further purification. Yield: 38 $ d * Th _e mp. 201-205 ⁰ C

C ₁₉ H ₂₀ K ₂ O ₅ S ₂ (420.5) Ber. C 54.27 H 5.04 K 6.66 S 15.25

C 54.22 H 5.93 N 6.54 S 14.88 JJV-51.6 (o * O, 85, DMSO)

Ajugf ühru ngsbeispiel 5

6 "- (β-D-glucopyranosylthio) -4- (p -ethoxy-phenyl) -2-methylthio-pyridine-3-carbonitrile ^

0.002 moles of 6- (2,3,4,6-tetra-O-acetyl-.beta.-D-glucopyranosylthio) -4- (p-methoxy-3-phenyl) -2-methylthio-pyridine-3-carbonitrile are deacetylated as described under Example 4 is described. Yield ι 6Ο9 & d.Th. Mp 232-235 ⁰ C

₆ S ₂ (450.5) Ber _e C 50.65 H 4.47 K 6.22

Found. C 50.52 H 4.93 K 6.16 -49.8 (c = 0.85, DMSO) \

Claims (1)

Invention Claim> A process for the preparation of S-HJrlucosiden of the general formula III in which R is an optionally alkyl-, halogen- or alkoxy-substituted phenyl radical, characterized in that Fyridincarbonitrile of the general formula I, in which R has the above meaning, with 2.3 , 4,6-Tetra-O-acetyl-β-D-glucopyranosylmercaptan in the presence of alkalis to give the acetylated S-glucosides of general formula II in which R is as defined above, and these are subsequently deacetylated. For this 1 page formulas