CS238791B1 - Process for preparing (Z) -3- (hydroxymethylene) -5-methyldihydro-2- (3H) -furanone sulfonates and carboxylates - Google Patents

Abstract

A method for preparing sulfonates and carboxylates of (Z)-3-(hydroxymethylene)-5-methyldihydro-2(3H)-furanone of the general formula I, H (I) h3c Ό where X denotes a substituent, which are prepared by treating the sodium salt of (Z)-3-(hydroxymethylene)-5-methyldihydro-2(3H)-furanone with chlorides or bromides or anhydrides of carboxylic or sulfonic acids at low temperatures. Sulfonates and carboxylates of (Z)-3-(hydroxymethylene)-5-methyldihydro-2(3H)-furanone are configurationally stable reactive compounds with extensive synthetic use, which can be considered as substances with potential antitumor activity and as starting substrates for the preparation of substances with potential antitumor activity.

Description

The present invention relates to a process for the preparation of (Z) -3- (hydroxymethylene) -5-methylidhydro-2 (3H) -furanone sulfonates and carboxylates.

Sulfonates and carboxylates of (Z) -3- (hydroxymethylene) -5-methyl-dihydro-2 (3H) -furanone are configurationally stable, reactive compounds with extensive synthetic use (Jonas J., Mazal C .: Coll.Czech. Chem. Commun.). In particular, they can be used to prepare a wide variety of 3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone derivatives having a Z configuration. Based on structural similarity to 3- (hydroxymethylene) dihydro-2 (3H) sulfonates and carboxylates T-furanone for which antitumor activity has been demonstrated (Stang. PJ, Treptéw WL:

J. Med. Chem. 24, 468 (1981)), may be considered to have potential antitumor effects.

They are not yet described in the literature; in the work (Vaidya AR, Gogte VN, Tilak BD Indian J. Chem. 15B. 403 (1977)) described 4-toluenesulfonate, which the authors have assigned to the Z configuration, has the structure (E) -3- (4-toluenesulfonyloxymethylene) -5- methyldihydro-2 (3H) -furanone, as evidenced by Mazal C., Roth V. and Jonas J. (Coli. Czech. Chem. Commun. 50 (1985)).

Now we found a method of preparation of sulfonates and carboxylates (Z) -3- (hydroxymethylene) -5-metyldihydro-2 (3H) -furanone of the formula I H ₃ C - ^<X ° and _about OX (I) wherein X is acetyl, mono- to trichloroacetyl, mono- to tribromoacetyl, trifluoroacetyl, propionyl, butyroyl, isobutyroyl, cyclohexanecarbonyl, 1-adamantanecarbonyl, benzoyl, 4-nitrobenzoyl, 4-fluorobenzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, phenylacetyl ,. methanesulfonyl, trifluoromethanesulfonyl, benzenesulfonyl, 4-toluenesulfonyl, 4-bromobenzenesulfonyl, 1-naphthalenesulfonyl or 2-naphthalenesulfonyl, which is simple and provides very good yields.

The compounds of the formula I according to the invention can be prepared by reacting the (Z) -3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone sodium salt with the corresponding carboxylic or sulfonic acid chloride of the formula II,

X-Cl (II) wherein X is as defined above for carboxylic or sulfonic acids of formula

I, or the corresponding bromide III,

X-Br (III) wherein X is as defined for xylic or sulfonic acid of formula IV,

I, or the corresponding carbohydrate (X ₂ ) o (IV) wherein X has the same meaning as the compounds of formula I, in molar ratios of 1: 1 to 3 at -50 _µ to -80 ° C.

He did

To a suspension of 1 g of sodium in 30 ml of diethyl ether was added 0.1 ml of ethanol, followed by dropwise addition of 4.5 g of β-valerolactone and 3.5 g of ethyl formate in 30 ml with stirring and cooling to -15 to -25 ° C. diethyl ether for 4 hours. The mixture in which the (Z) -3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone sodium salt precipitated gradually, then was cooled to -75 ° C, was poured into it beforehand at -75 ° C a cooled solution of 0.045 mol of trifluoromethanesulfonic anhydride (a compound of formula IV wherein X is trifluoromethanesulfonyl) in 125 mL of acetone and stirring and cooling was continued for 5 hours. Upon reaching room temperature, 58% of (Z) -3- (trifluoromethanesulfonyloxymethylene) -5-methyldihydro-2 (3H) -furanone (compound of formula I where X is F-IC 50) is isolated from the mixture, m.p. 43-44 ° C.

Example 2

To a suspension of 1 g of sodium in 30 ml of diethyl ether was added 0.1 ml of ethanol, and then, while stirring and cooling to -15 to -25 ° C, a solution of 4.5 g of β-valerolactone and 3.5 g of ethyl formate in 30 ml was added dropwise. diethyl ether for 4 hours. The mixture was then cooled to -75 ° C and poured into a previously -75 ° C cooled solution of 0.045 moles of benzenesulfonyl chloride, (a compound of formula II where X is C 8 H 8 SO 8) in 125 ml of acetone and continued cooling and stirring. hours. Upon reaching room temperature, pure (Z) -3- (benzenesulfonyloxymethylene) -5-methyldihydro-2 (3H) -furanone (compound of formula I wherein X is C 8 H 8 SO 8) was isolated from 3 mixture, m.p. 70-72 ° C. yield 65%.

Example 3

To a suspension of 1 g of sodium in 30 ml of diethyl ether was added 0.1 ml of ethanol, and then, with stirring and cooling to -15 to -25 ° C, a solution of 4.5 g of β-valerolactone and 3.5 g of ethyl formate in 30 ml was added dropwise. diethyl ether for 4 hours. The mixture was then cooled to -75 ° C, a pre-cooled solution of 0.045 mol of 4-toluenesulfonyl chloride (of the formula II wherein X is 4-CH 3 Cl ₂ H ₂ SO ₂ ) in 125 ml of acetone was poured into it. in cooling and stirring for 7 hours. Upon reaching room temperature, pure (Z) -3- (4-toluenesulfonyloxymethylene) -5-methyldihydro-2 (3H) -furanone (compound of formula I wherein X is 4-CH 2 C 8 H 4 SO ₂ ) was isolated from the mixture, m.p. 125-227 ° C, yield 58%. Example 4

To a suspension of 1 g of sodium in 30 ml of diethyl ether was added 0.1 ml of ethanol, and then, while stirring and cooling to -15 to -25 ° C, a solution of 4.5 g of f-valerolactone and 3.5 g was added dropwise. Ethyl formate in 30 ml diethyl ether for 4 hours. The mixture was cooled to -75 ° C, poured into a pre-cooled solution of 0.045 mol of 2-naphthalenesulfonyl chloride (a compound of formula II wherein X is 2-C, qH ₂ SO ₂ ) in 150 mL of acetone and cooling and stirring was continued for 8 hours.

Upon reaching room temperature, 65% of (Z) -3- (2-naphthalenesulfonyloxymethylene) -5-methyldihydro-2 (3H) -furanone (compound of formula I where X is 2-C _{) O} HySO ₂ was isolated from the mixture, mp 107-107.5 ° C.

Example 5

To a suspension of 1 g of sodium in 30 ml of diethyl ether, 0.1 ml of ethanol was added, followed by the dropwise addition of 4.5 g of? -Valerolactone and 3.5 g of ethyl formate in 30 ml of diethyl ether while stirring and cooling to -15 to 24 ° C. for 4 hours. The mixture was cooled to -75 ° C, a pre-cooled solution of 0.045 mole of acetyl bromide (of the formula III where X is CH 2 CO) in 25 ml of acetone was poured into it, and cooling and stirring was continued for 10 minutes. hours.

After reaching room temperature, 40% of (Z) -3- (ecetoxymethylene) -5 was isolated from the mixture

methyldihydro-2 (3H) -furanone (compound of formula 1 wherein X is CH 2 CO), m.p. 62-65 ° C.

Example 6

To a suspension of 1 g of sodium in 30 ml of diethyl ether, 0.1 ml of ethanol was added, followed by the dropwise addition of 4.5 g of β-valerolactone and 3.5 g of ethyl formate in 30 ml with stirring and cooling to -15 to -25 ° C. diethyl ether for 4 hours. The mixture was cooled to

-75 ° C, was poured into a pre-cooled solution of 0.045 mol of henzoyl chloride (a compound of formula II where X is C 1 H 4 CO) in 125 ml of acetone and continued to cool and stir for 5 hours. Upon reaching room temperature, 64% of (Z) -3- (benzoyloxymethylene) -5-methyldihydro-2 (3H) -furanone (compound of formula I, where

X is CH (100), mp 127-129 ° C.

?

Example 7

To a suspension of 0.66 g of sodium in 20 ml of diethyl ether, 0.1 ml of ethanol was added, and then a solution of 3.0 g of -valerolactone and 2.4 g of ethyl formate in 20 ml was added dropwise with stirring and cooling to -15 to -25 ° C. ml of diethyl ether for 4 hours. The mixture was then cooled to -75 ° C, poured into a pre-cooled solution of 0.060 mol of phenylacetyl chloride (a compound of formula II where X is G 8 H 3 CH 2 CO) in 150 ml of acetone and cooled and stirred for 8 hours. Upon reaching room temperature, pure (Z) -3- (phenylacetoxymethylene) -5-methyldihydro-2 (3H) -furenone (compound of formula I wherein X is C 8 H 6 CH 2 CO) was isolated from the mixture, mp 112-114 ° C , in 68% yield.

Other compounds of the formula I can be prepared in the same manner using the compounds II to IV.

Claims (1)

SUBJECT OF THE INVENTION A process for the preparation of (Z) -3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone sulfonates and carboxylates of the formula I, H ₃ C ox Ό (I) wherein X represents acetyl, mono- to trichloroacetyl, mono- to tribromoacetyl, trifluoroacetyl, propionyl, butyroyl, isobutyroyl, cyclohexanecarbonyl, 1-adamantanecarbonyl, benzoyl, 4-nitrobenzoyl, 4-fluorobenzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-bromobenzoyl , phenylacetyl, methanesulfonyl, trifluoromethanesulfonyl, benzenesulfonyl, 4-toluenesulfonyl, 4-bromobenzenesulfonyl, 1-naphthalenesulfonyl or 2-naphthalenesulfonyl, characterized in that the sodium salt of (Z) -3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone is treated with the corresponding carboxylic or sulfonic acid chloride of the formula II, X-Cl (II) wherein X is as defined for compounds of formula I, or the corresponding carboxylic or sulfonic acid bromide of formula III, X-Br (III) wherein X has the same meaning as in the compounds of formula I, or a corresponding anhydride, carboxylic or sulfonic acid of formula IV (X ₂₎ 0 (IV) wherein X has the same meaning as in compounds of general formula I, molar ratios of 1: 1 to 3 at -50 to -80 ° C.