CS247563B1 - Process for preparing (Z) -3- (hydroxymethylene) -hexahydro-2 (3H) -benzofuranone sulfonates and carboxylates - Google Patents

Abstract

A method for preparing carboxylates and sulfonates of (Z)-3-(hydroxymethylene)hexahydro-2(3H)-benzofuranone of formula I where X denotes acetyl, benzoyl, 4-toluenesulfonyl, which are prepared by treating the sodium salt of (Z)-3-(hydroxymethylene)hexahydro-2(3H)-benzofuranone in an organic solvent, such as acetone, diethyl ether or tetrahydrofuran, at a temperature of -10 to -25 °C, with chlorides or bromides or anhydrides of carboxylic or sulfonic acids of the general formula XC1 or XBr or XOX, where X has the meaning given above and ». Sulfonates and carboxylates of (Z)-3-(hydroxymethylene)hexahydro-2(3H)-benzofuranone are reactive compounds with extensive synthetic use, which can be considered as substances with potential antitumor activity and as starting substrates for the preparation of other substances with this activity.

Description

The present invention relates to a process for the preparation of (Z) -hydroxymethylene) hexahydro-2 (3H) -benzofuranone sulfonates and carboxylates. Sulfonates and carboxylates of (Z) -3- (hydroxymethylene) hexahydro-2- (3H) -benzofuranone are reactive compounds with extensive synthetic uses (Jona J., Mazal C.: Coll.Czech.Chem.Commun.). Based on structural details, 3- (hydroxymethylene) dihydro-2 (3H) -furanone sulfonates and cyrboxylates have been shown to have antitumor activity (Stang PJ, Trepow WL: J. Med. Chem. 24, 469 (1981)). The preparation processes described so far in the literature lead to mixtures of (E) and (Z) isomers of 4-toluenesulfonate (Howie GA: Stamos IK, Cassady J. Med. Chem. 19,

309 (1976) or mixtures of (E) and (Z) isomers of methanesulfonate and trifluoromethanesulfonate (Stang P.J., Treptow W.L .: J. Med. Chem. 24, 468 (1981)) which were separated by crystallization or by chromatography.

We have now found a process for the preparation of (Z) -3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sulfonates and carboxylates of formula I

OX (i) wherein X represents acetyl, benzoyl, methanesulfonyl, trifluoromethanesulfonyl, benzenesulfonyl, 4-toluenesulfonyl. This process is simple and provides satisfactory yields of pure (Z) -isomers. The compounds of formula (I) according to the invention can be prepared by reacting a suspension of (Z) -3 (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sodium salt in an organic solvent such as diethyl ether, acetone or tetrahydrofuran with 1 to 1.3 times the molar amount of of a carboxylic or sulfonic acid chloride or bromide or anhydride of the formula XCl or XBr or XOX, wherein X is as defined above, at -10 to -25 ° C.

Example 1

To a suspension of 1 g of (Z) -3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sodium salt in 80 ml of -12 ° C diethyl ether was added 0.5 ml of acetyl bromide with stirring. The mixture was stirred with cooling for 24 hours. After filtering and evaporating the ether, 0.62 g of (604) (Z) -3- (acetyloxymethylene) hexahydro-2 (3H) -benzofuranone (compound of formula I where X is CHgCO) is obtained, m.p. C.

Example 2

To a suspension of 1 g of (Z) -3- (hydroxymethylethylene) hexahydro-2 (3H) -benzofuranone sodium salt in 100 ml of -18 ° C diethyl ether was added 0.6 ml of benzoyl chloride with stirring.

The mixture was stirred with cooling for 20 hours. Working up the reaction mixture after reaching room temperature gave 1.01 g of (72%) (Z) -3- (benzoyloxymethylene) -hexahydro-2,3H) -benzofuranone (a compound of formula X wherein Y is C8H3CO), m.p. 139 [deg.] C.

Example 3

To a suspension of 1 g of (Z) -3- (hydroxymethylene) hexahydro-2 (3H) -benzoruranone sodium salt in 100 mL of -15 ° C diethyl ether was added with stirring 1.1 mL of trifluoromethanesulfonic anhydride. The mixture was stirred under cooling for 24 hours and then worked up at room temperature.

1.2 g of (754) (Z) -3- (trifluoromethanesulfonyloxymethylene) hexahydro-2 (3H) -benzofuranone (compound of formula I wherein X is CF-SO2) were obtained, m.p. 121-124 ° C.

Example 4

To a suspension of 1 g of (Z) -3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sodium in 100 ml of -12 ° C acetone was added 0.5 ml of methanesulfonyl chloride with stirring, and the mixture was stirred at this temperature. hours. Treatment of the reaction mixture at room temperature gave 0.75 g (60%) of (Z) -3- (methanesulfonyloxymethylene) hexahydro-2- (3H) -benzofuranone (compound of formula I wherein X is CH3SO2), m.p. 118 ° C.

Example 5

To a suspension of 1 g of (Z) -3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sodium in 60 ml of -15 ° C tetrahydrofuran was added a solution of 1.2 g of 4-toluenesulfonyl chloride in 40 ml of tetrahydrofuran with stirring. the same temperature. The mixture was further stirred under cooling and worked up at room temperature after 24 hours. 1.2 g (73%) of (Z) -3- (4-toluenesulfonyloxymethyl) hexahydro-2 (3H-benzofuranone) (compound of formula I wherein X is CH CHCgH ^SC ^) were obtained, m.p. 157-159 Deň: 32 ° C.

Example6

To a suspension of 1 g of (Z) -3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sodium in 100 ml of diethyl ether at -10 ° C was added 0.75 ml of benzosulfonyl chloride with stirring. Stirring was continued at the same temperature for 20 hours and then the reaction mixture was worked up at room temperature. Yield 0.95 g (70%) of (Z) -3- (benzensulfonyloxymetylen) hexahydro-2 (3H) -benzofuranonu (compound of formula I, wherein X stands CgHgSO _2), mp 115-118 ° C.

Claims (1)

SUBJECT OF THE INVENTION A process for the preparation of (Z) -3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sulfonates and carboxylates of the formula (I) O wherein X is acetyl, benzoyl, methanesulfonyl, trifluoromethanesulfonyl, benzosulfonyl, 4-toluenesulfonyl, (Z) -3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sodium is treated at -10 to -25 ° C in an organic solvent such as diethyl ether, acetone or tetrahydrofuranone with 1 to 1.3 times molar amount or a sulfonic or carboxylic acid chloride or bromide or anhydride of formula XCl or XBr or XOX, wherein X is as defined above.