CS238791B1 - Processing of/z/-3-hydromethylen/-5-methyldihydro-2/3h/furanone sulphonate and carboxylate - Google Patents

Abstract

Process for preparing sulfonates and carboxylates (Z) -3- (Hydroxymethylene) -5-methyldihydro-2 (3H) -furanone formula I, H (I) h3c Ό wherein X represents a substituent to be prepared by treating sodium salt of (Z) -3- (hydroxymethylene) -5-methyldihydro-2,3H) -furanone chlorides or bromides or anhydrides carboxylic or sulfonic acids at low temperatures. Sulfonates a carboxylates of (Z) -3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone are configurable stable reactive compounds with a wide range synthetic use that can be potential anticancer agents and the starting substrates for the preparation of potential antitumor agents effect.

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.