CS248916B1 - Process for preparing (E) -3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sulfonates and carboxylates \ t - Google Patents

Abstract

A method for preparing sulfonates and carboxylates of (E)-3- (hydroxymethylene) hexahydro-2 (3H)-benzofuranone of formula I OX (1), where X is acetyl, benzoyl, methanesulfonyl, trifluoromethanesulfonyl, benzenesulfonyl, 4-toluenesulfonyl, which are prepared by treating a 1% to saturated solution of the sodium salt of 3- (hydroxymethylene) hexahydro-2 (3H)-benzofuranone in a polar solvent, such as aqueous acetone, aqueous tetrahydrofuran and water, in the presence of a nitrogenous base, with chlorides or bromides or anhydrides of sulfonic or carboxylic acids of the general formula XC1 or XBr or XOX, where X has the meaning given above. Sulfonates and carboxylates of (E)-3-(hydroxymethylene)-hexahydro-2('3H)-benzofuran are reactive compounds with extensive synthetic use, which can be considered as substances with potential antitumor effects and as starting substrates for the preparation of other substances with these effects.

Description

The present invention relates to a process for the preparation of (E) -3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sulfonates and carboxylates.

The sulfonates and carboxylates of (E) -3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone are reactive compounds with extensive synthetic use (Jonas J., Mazal C .: Coll. Chem. Commun./. Based on structural similarity to the sulfonates and carboxylates of 3- (hydroxymethylene) dihydro-2 (3H) -furanone for which antitumor activity has been demonstrated (Stang P.J.,

Treptow, W.L .: J. Med. Chem. 24, 469 (1981)], may be considered to have potential antitumor effects.

The preparation methods described so far in the literature lead to mixtures of (E) and (Z) 4-toluenesulfonate isomers (Howie, G.A., Stamos, I.K., Cassady, JM, J. Med. Chem. 19, 309 (1976)] or to mixtures (E) and (Z) of isomers of the methanesulfonate and trifluoromethanesulfonate (Stang, P.J., Treptow, W.L .: J. Med. Chem. 24, 469 (1981)], which were separated by crystallization or by chromatography.

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

OX

wherein X is acetyl, benzoyl, ethanesulfonyl, trifluoromethanesulfonyl, benzenesulfonyl, 4-toluenesulfonyl. This process is simple and provides satisfactory yields of the pure (E) -isomers. The compounds of formula (I) may be prepared by reacting a solution of 1% to saturated, 3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sodium salt with 1 to 1.3 times the molar amount of the corresponding sulfonic or carboxylic acid chloride or bromide or anhydride of the formula XC1 or XBr or XOX, wherein X is as defined above, in the presence of a nitrogenous base such as trlethylamine, tributylamine or pyridine.

Example 1

1 g of 3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sodium salt was dissolved in a mixture of 100 ml of aqueous acetone and 0.8 ml of triethylamine. While stirring at room temperature, 0.5 mL of acetyl bromide was added. After stirring for 5 hours, the reaction mixture was worked up to give 0.76 g (72%) of (E) - (acetyloxymethylene) hexahydro-2 (3H) -benzofuranone (compound of formula I wherein X is CH 2 CO), boiling point. 160-165 ° C at 1.46 kPa.

Example 2

1 g of 3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sodium salt was dissolved in a mixture of 100 ml of aqueous tetrahydrofuran and 0.9 ml of triethylamine. While stirring at room temperature, 0.6 ml of benzoyl chloride was added. After stirring for 4 hours, the reaction mixture was worked up to give 0.9 g (63%) of (E) -3- (benzoyloxymethylene) hexahydro-2 (3H) benzofuranone (compound of formula I wherein X is C8 HgCO), m.p. 163 to 165 ° C.

Example 3

1 g of 3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sodium salt was dissolved in a mixture of 100 ml of aqueous tetrahydrofuran and 1.3 ml of tributylamine. While stirring at room temperature, 1.1 mL of trifluoromethanesulfonic anhydride was added. After stirring for 6 hours, the reaction mixture was worked up to give 1.05 g (68%) of (E) -3- (trifluoromethanesulfonyloxymethylene) hexahydro-2 (3H) -benzofuranone (compound of formula I wherein X is CF ₃ SO ₂ ) mp 84-87 ° C.

Example 4

1 g of 3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sodium salt was dissolved in a mixture of 100 ml of aqueous acetone and 1.3 ml of tributylamine. While stirring at room temperature, 0.5 mL of methanesulfonyl chloride was added. After stirring for 5 hours, the reaction mixture was worked up to give 0.72 g (58%) of (E) -3- (methanesulfonyloxymethylene) -hexaliydro-2 (3H) -benzofuranone) compound of formula I wherein X is CH ₃ SO ₂ mp 103-106 ° C.

Example 5

1 g of 3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sodium salt was dissolved in a mixture of 100 ml of aqueous acetone and 0.5 ml of pyridine. While stirring at room temperature, 0.75 ml of benzenesulfonyl chloride was added. After stirring for 4 hours, the reaction mixture was worked up to give 0.85 g (54%) of (E) -3- benzenesulfonyloxymethylene (hexahydro-2 (3H) -benzofuranone) of the compound of formula I wherein X is C8 H5 SO3. mp 62-65 ° C.

Example 6

1 g of 3- (hydroxymethylene) hexahydro-2 (3H) -benzofuranone sodium salt was dissolved in a mixture of 100 ml of aqueous acetone and 0.5 ml of pyridine. While stirring at room temperature, a solution of 1.2 g of 4-toluenesulfonyl chloride in 50 ml of aqueous acetone was added. After stirring for 6 hours, the reaction mixture was worked up to give 1.05 g (63%) of (E) -3- (4-toluenesulfonyloxymethylene) hexahydro-2 (3H) -benzofuranone) compound of formula I wherein X is CH ₃ CgH ? SO ₂ /, mp 87-89 ° C.

Claims (1)

Process for the preparation of sulfonates and carboxylates of (E) -3- (hydroxymethylene) -hexahydro-2 (3H) -benzofuranone of the formula I OX wherein X is acetyl, benzoyl, methanesulfonyl, trifluoromethanesulfonyl, benzenesulfonyl, 4-toluenesulfonyl, suppressed by the addition of a 1 to a saturated solution of 3- (hydroxymethylene) -hexahydro-2 (3H) -benzofuranone sodium in a polar solvent such as aqueous acetone, aqueous tetrahydrofuranone and water are treated in the presence of a nitrogenous base with a 1 to 1.3 fold molar amount of sulfonic acid chloride or bromide or anhydride of formula XCl or XBr or XOX, wherein X is as defined above.