CS253312B1 - Process for preparing (Z) -3- (hydroxymethylene) - dihydro-2 (3H) -furanone sulfonates and carboxylates - Google Patents

Abstract

The subject of the solution is a method for preparing sulfonates and carboxylates of (Z)-3-(hydroxymethylene)dihydro-2(3H)-furanone of the general formula X where X denotes a substituent. Compounds of the general formula I are prepared by treating the sodium salt of (Z)-3-(hydroxymethylene(dihydro)-2(3H)-furanone with chlorides or bromides or anhydrides of the corresponding sulfonic or carboxylic acids at temperatures of -40 to -80 °C. Sulfonates and carboxylates of (Z)-3-(hydroxymethylene)dihydro-2-(3H)-furanone are reactive compounds with extensive synthetic use; some of them have antitumor effects.

Description

The present invention relates to the preparation of (Z) -3- (hydroxymethylene) dihydro-2 (3H) -furanone sulfonates and carboxylates.

(Z) -3- (hydroxymethylene) dihydro-2 (3H) -furanone sulfonates and carboxylates (Jonas J .: Coll. Czech. Chem. Commun. 49, 1 907 (1984)) are reactive compounds with extensive synthetic use (Mazal C., Jurka J., Jonas J .: Coll. Czech. Chem. Commun.), Including substances with antitumor activity (Stang PJ, Treptow WK: J. Med. Chem. 24, 468 (1981)).

Direct preparation of these compounds in pure form is not described in the literature. The disclosed (Z) -3- (hydroxymethylene) dihydro-2 (3H) -furanone sulfonates are obtained by laborious separation of mixtures of (E) and (Z) -isomers (Stang PJ, Treptow WLi J. Med. Chem. 24, 468 (1981) )).

According to the invention, a process for the preparation of (Z) -3- (hydroxymethylene) dihydro-2 (3H) -furanone sulfonates and carboxylates of the formula I has been found,

H

ΌΧ wherein X represents acetyl, mono- to trichloroacetyl, mono- to tribromoacetyl, trifluoroacetyl, propionyl, butyroyl, isobutyroyl, cyclohexanecarbonyl, 1-adamantancarbonyl, benzoyl, 4-nitrobenzoyl, 4-fluorobenzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-bromobenzoyl, 4-bromobenzoyl, methanesulfonyl, trifluoromethanesulfonyl, benzenesulfonyl, 4-toluenesulfonyl, 4-bromobenzenesulfonyl, 1-naphthalenesulfonyl or 2-naphthalenesulfonyl, which provides high yields of configuration-pure products. Compounds of formula I may be prepared by reacting the sodium salt of (Z) -3- (hydroxymethylene) dihydro-2 (3H) -furanone with the chlorides or bromides or anhydrides of the corresponding sulfonic or carboxylic acids at temperatures of -40 to -80 ° C.

He did

To a suspension of 3.5 g of sodium in 50 ml of diethyl ether was added 0.3 ml of ethanol, and then, while stirring and cooling to -10 to -30 ° C, a solution of 13 g of gamma-butyrolactone and 12 g of ethyl formate in 40 ml of diethyl ether was gradually added. for 6 hours. The mixture in which the precipitate of the (Z) -3- (hydroxymethylene) dihydro-2 (3H) -furanone sodium salt was gradually precipitated, was then cooled to -75 ° C, was poured into the previously cooled solution 0 ° C. 15 mole of acetyl bromide in 400 ml of acetone and after stirring and cooling for 90 minutes the mixture was left without cooling until room temperature was reached. The acetone was distilled off under reduced pressure and aspirated to give 65% of (Z) -3- (acetoxymethylene) dihydro-2 (3H) -furanone (compound of formula I wherein X is CH ₃ CO), m.p. 92-93.5 Deň: 32 ° C.

Example 2

To a freshly prepared suspension of 0.15 mol of (Z) -3- (hydroxymethylene) dihydro-2 (3H) -furanone sodium salt in 90 ml of diethyl ether at -75 ° C was poured a pre-cooled solution of 0.15 mol at -75 ° C. of benzoyl chloride in 400 ml of acetone and the mixture was stirred and cooled for 90 minutes. Upon reaching room temperature, 90% of (Z) -3- (benzoyloxymethylene) dihydro-2 (3H) -furanone (compound of formula I wherein X is C ^H ^CO CO) was isolated from the mixture, m.p. 142-143 °. C.

Example 3

A freshly prepared suspension of 0.15 mole of (Z) -3- (hydroxymethylene) dihydro-2 (3H) -furanone sodium salt in 90 ml of diethyl ether was mixed at -75 ° C with a solution of 0.15 mole of phenylacetyl chloride in 40 ml of acetone. was pre-cooled to -75 ° C, and the mixture was stirred and cooled for 90 minutes. Upon reaching room temperature, 88% of (Z) -3- (phenylacetoxymethylene) dihydro-2 (3H) -furanone (compound of formula X wherein X is C 8 H 8 CH 3 CO) was isolated from the mixture, mp 119-120 ° C.

Example 4

A freshly prepared suspension of 0.15 mol of (Z) -3- (hydroxymethylene) dihydro-2 (3H) -furanone sodium salt in 90 ml of diethyl ether was mixed with a pre-cooled solution of 0.15 mol at -75 ° C at -75 ° C. of methanesulfonyl chloride in 400 ml of acetone and the mixture was stirred and cooled for 90 minutes. After reaching room temperature, 87% of (Z) -3- (methanesulfonyloxymethylene) dihydro-2 (3H) -furanone (compound of formula I wherein X is CH 2 SO 4) was isolated, m.p. 93-94 ° C. .

Example 5

A solution of 0.15 mol trifluoromethanesulfonylanhydride in 400 ml acetone was cooled to -75 ° C and poured into a freshly prepared suspension of 0.15 mol of (Z) -3- (hydroxymethylene) dihydro-2 (3H) -furanone sodium salt in 90 ml diethyl ether with cooling to -75 ° C. The mixture was cooled and stirred for 90 minutes, then allowed to reach room temperature. The acetone was distilled off under reduced pressure, the precipitated oil was extracted into chloroform, from which 76% of (Z) -3- (trifluoromethanesulfonyloxymethylene) dihydro-2 (3H) -furanone (compound of formula I wherein X is CF ₃ SO ₂₎ ¹ H NMR = CH, 6.97 (CDCl 3), J = 2.5 Hz.

Example 6

A freshly prepared suspension of 0.15 mol of (Z) -3- (hydroxymethylene) dihydro-2 (3H) -furanone sodium salt in 90 ml of diethyl ether was stirred at -75 ° C with a solution of 0.15 mol of benzenesulfonyl chloride in 400 ml of acetone of the same The mixture was stirred and cooled for 90 minutes. Upon reaching room temperature, 65% of (Z) -3- (benzenesulfonyloxymethylene) dihydro-2 (3H) -furanone (compound of formula I wherein X is C ^H ^SC ^) was isolated from the mixture, mp 133-134 ° C C.

Example 7

A solution of 4-bromobenzoyl chloride (0.15 mol) in acetone (400 ml) was cooled to -75 ° C and poured into a freshly prepared suspension of (Z) -3- (hydroxymethylene) dihydro-2 (3H) -furanone sodium salt (0.15 mol) in 90 ml. ml of diethyl ether at -75 ° C. The mixture was cooled and stirred for 90 minutes and after reaching room temperature, 94% of (Z) -3- (bromobenzoyloxymethylene) dihydro-2 (3H) -furanone (compound of formula I wherein X is 4-BrCgH 4 CO) was isolated therefrom. mp 102-103.5 ° C.

Example 8

A freshly prepared suspension of 0.15 mol of (Z) -3- (hydroxymethylene) dihydro-2 (3H) -furanone sodium salt in 90 ml of diethyl ether was cooled to -75 ° C and mixed, with a pre-cooled solution of -75 ° C. 0.15 mol of 4-toluenesulfonyl chloride in 400 ml of acetone. The mixture was stirred and cooled for 90 minutes, and after reaching room temperature, 90% of (z) -3- (toluenesulfonyloxymethylene) dihydro-2 (3H) -furanone (compound of formula I wherein X is 4-CH ₃ CgH ₄₎ SO _2), mp 145.5 to 146.5 ° C.

Example 9 '

A solution of 0.15 mol of 2-naphthalenesulfonyl chloride in 400 ml of acetone, cooled to -75 ° C, was poured into a freshly prepared suspension of 0.15 mol of (Z) -3- (hydroxymethylene) dihydro-2 (3H) -furanone sodium salt in 90 ml of diethyl ether at -75 ° C. The mixture was stirred and cooled for 90 minutes, allowed to reach room temperature and concentrated in vacuo. 87% of (Z) -3- (naphthalenesulfonyloxymethylene) dihydro-2 (3H) -furanone (compound of formula I wherein X is 2-C ₁₀ H ₇ SC ₂ ) were obtained, m.p. 137-138.5 ° C. .

Claims (1)

OBJECT OF THE INVENTION A process for the preparation of (Z) -3- (hydroxymethylene) dihydro-2 (3H) -furanone sulfonates and carboxylates of formula I, ΌΧ wherein X represents acetyl, mono- to trichloroacetyl, mono- to tribromoacetyl, trifluoroacetyl, propionyl, butyroyl, isobutyroyl, cyclohexanecarbonyl, 1-adamantancarbonyl, benzoyl, 4-nitrobenzoyl, 4-fluorobenzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-bromobenzoyl, 4-bromobenzoyl , methanesulfonyl, trifluoromethanesulfonyl, benzenesulfonyl, 4-toluenesulfonyl, 4-bromobenzenesulfonyl, 1-naphthalenesulfonyl or 2-naphthalenesulfonyl, characterized in that (Z) -3- (hydroxymethylene) dihydro-2 (3H) -furanone sodium salt is present. act with the chlorides or bromides or anhydrides of the corresponding sulfonic or carboxylic acids at temperatures of -40 to -80 ° C. Severography, n. P., MOST Price 2,40 Kčs