CS239409B1 - Preparation method of sulphonates andcarboxylates /e/-3-hydroxymethylene /-5-methyldihydro-2/3h/-furanone - Google Patents

Abstract

Process for preparing sulfonates and carboxylates (E) -3- (hydroxymethylene) -5-methyldihydro- -2 (3N) -furanone of formula (I) OX (I) -Λ-ο h3c o wherein X is acetyl, mono- to trichloroacetyl, mono- to tribromoacetyl, trifluoroacetyl, propionyl, butyroyl, isobutyroyl, cyclohexanecarbonyl, 1-adamantanecarbonyl, benzoyl, 4-nitrobenzoyl, 4-fluorocarbonyl, 4-chlorophenyl benzoyl, 4-bromenzyl, phenylacetyl, methanesulfenyl, trifluoromethanesulfenyl, bonzenaulfonyl, 4-teluensulphenyl, 4-brembonsonsulphonyl, , -naphthalonsulfonyl or 2-Naphthalenesulfonyl, characterized in that to sodium 3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone chlorides, sulfonic bromides or enhydrides; \ tor. \ t carboxylic acids in solution under catalysis nitrogen base. Sulfonates and carboxylates (E) -3- (hydroxymethylene) -5-methyldihydro- -2 (3 R) -furanone are reactive compounds with a potential antitumor effect. They are also starting substrates for preparation potential anticancer agents effect.

Description

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

Sulfonates and carboxylates of (E) -3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone are reactive, configuration-stable compounds with extensive synthetic utilization (Vaidya AR, Oogte VN, Tilak BD: Indian J. Chem. 15B. 403-407 (1977); Jonas J., Mazal C .: Coll. Czech. Chem. Commun.). Based on significant structural similarity to 3- (hydroxymethylene) dihydro-2 (3H) -furanone sulfonates and carboxylates for which antitumor activity has been demonstrated (Stang PJ, Treptow WL: J. Med. Chem. 24. 468 (1981)), they can be considered as substances with potential antitumor effects and as starting compounds for the preparation of substances with potential antitumor effects. In the literature (Vaidya, A.R. et al., Supra), the preparation of so far the only compound of this series, 4-toluenesulfonate, whose incorrectly attributed configuration has been corrected (Mazal C., Roth V., Jonas J .: Coll.

Czech. Chem. Commun. 50 (1985)) is lengthy and unsatisfactory in terms of yield.

A process for preparing sulfonates and carboxylates of (E) -3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone of general formula I has now been found.

OX (I) h ₃ c wherein X represents acetyl, mono-trichloroacetyl, mono- to tribromoacetyl, trifluoroacetyl, propionyl, butyroyl, isobutyroyl, cyclohexanecarbonyl, 1-edamentanecarbonyl, 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 of compounds of formula I in a short time. The compounds of formula (I) may be prepared by reacting the sodium salt of 3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone with the corresponding carboxylic or sulfonic acid chloride of formula (II),

X-Cl (II) wherein X is as defined for compounds of formula I, or the corresponding carboxylic acid or sulfonic acid bromide of formula III,

X-Br (III) wherein X has the same meaning as in sloučeninObecného formula I, or a corresponding anhydride of a carboxylic or sulfonic acid of formula 17 (X ₂₎ 0 (IV) wherein X has the same meaning as in the compounds of formula I in solution catalysing a nitrogen base, such as triethylamine, trimethylamine, pyridine or quinoline, at room temperature using equimolar amounts of starting materials or a 1.1 to 3-fold excess of any of the compounds of formula II or III or IV used, respectively. nitrogenous base.

He did

3- (Hydroxymethylene) -5-methyldihydro-2 (3H) -furanone sodium (1.5 g) was dissolved in 10 ml of water, 20 ml of acetone and 1 ml of triethylamine were added thereto, followed by 0.01 mol with stirring trifluoromethanesulfonic anhydride (a compound of formula IV wherein

X is CF (SO 2). After stirring at room temperature for 30 minutes, 63% of (E) -3- (trifluoromethanesulfonyloxymethylene) -5-methyldihydro-2 (3H) -furanone (compound of formula I wherein X is CF 3 SO ₂ ) was isolated, m.p. Deň: 29 ° C.

Example 2

Sodium salt of 3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone (1.5 g) was dissolved in 10 ml of water, 25 ml of acetone and 2.5 ml of a 25% aqueous trimethylamine solution were added thereto, followed by with stirring, 0.01 mol of methanesulfonyl chloride (a compound of formula II wherein X is CH-SO2). After stirring at room temperature for 30 minutes, 75% of (E) -3- (methanesulfonyloxymethylene) -5-methyldihydro-2 (3H) -furanone (compound of formula I wherein X is CH ₃ SO ₂ ) was isolated, m.p. Mp 71-72 ° C.

Example 3

A solution of 1.5 g of 3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone sodium in 10 ml of water was diluted with 20 ml of acetone, 1.15 ml of quinoline was added, followed by 0.01 mol of benzerisulfonyl chloride of formula (II) wherein X is C (H (SO 2)). After stirring at room temperature for 30 minutes, 69% of (E) -3- (benzenesulfonyloxymethylene) -5-methyldihydro-2 (3H) -furanone (compound of formula I wherein X is C 8 H 8 SO 8) was isolated, oil, 1 H NMR in CDCl 3: chemical shift = CH 7.65 (ppm), J = 3/0 (Hz).

He attaches

To a solution of 1.5 g of 3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone sodium salt in 10 ml of water was added 20 ml of acetone and 0.8 ml of pyridine, followed by a solution of 0.01 mol of 4- toluenesulfonyl chloride (II, wherein X is 4-CH ₃ C 9 H 4 SO ₂ ) in 25 mL of acetone-water (2: 1). After stirring at room temperature for 30 minutes, 70% of (E) -3- (4-toluene) -phonyloxymethylene) -5-methyldihydro-2 (3H) -furanone (compound of formula I wherein X is? -CH3CH) is isolated from the mixture. Mp 61-62 ° C.

Example 5

3- (Hydroxymethylene) -5-methyldihydro-2 (3H) -furanone sodium (1.5 g) was dissolved in 10 ml of water, 20 ml of acetone and 1 ml of triethylamine were added thereto, followed by 0.01 mol with stirring Of 2-naphthalenesulfonyl chloride (compound of formula II wherein X is 2-O-302) dissolved in 25 mL of acetone-water (2: 1). After stirring at room temperature for 30 minutes, 56% of (E) -3- (2-naphthalenesulfonyloxymethylene) -5-methyldihydro-2 (3H) -furanone (compound of formula I wherein X is 2-C -H ^H ^) was isolated from the mixture. M.p. 83-84 ° C. Example 6

To a solution of 3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone sodium salt (1.5 g) in 10 ml of water was added 20 ml of acetone and 1 ml of triethylamine, and then with stirring 0.01 mol of acetyl bromide ( of formula III wherein X is CH 2 CO 2. After stirring at room temperature for 30 minutes, 48% of (E) -3- (acetoxywethylene) -5-methyldihydro-2 (3H) -furanone (compound of formula I wherein X is βΗΗΟΟ), an oil, 1 H NMR in CDCl 3: chemical shift = CH 8.27 (ppm), J = 3.0 (Hz).

Example 7

A solution of 1.5 g of 3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone sodium in 10 ml of water was mixed with 20 ml of acetone and 1 ml of triethylamine and 0.01 mol of benzoyl chloride (substance) was added. of formula (II) wherein X is C 8 H 4 CO 2. After stirring at room temperature for 30 minutes, 68% of (E) -3- (benzoyloxymethylene) -5-methyldihydro-2 (3H) -furanone (compound of formula I wherein X is C8H4CO) was isolated from the mixture, mp 113 Mp 5-114 ° C.

Example

A solution of 1.5 g of 3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone sodium salt in a mixture of 10 ml of water, 20 ml of acetone and 1 ml of triethylamine was stirred and 0.01 moles was added thereto at room temperature. phenylacetyl chloride (a compound of formula II wherein X is C8H4CH2CO). After 30 minutes, 58% of (E) -3- (phenylecetoxymethylene) -5-methyldihydro-2 (3H) -furanone (compound of formula I wherein X is C8H4CHgCO) was isolated, m.p. 98-99 ° C. .

Claims (1)

SUBJECT OF THE INVENTION A process for the preparation of sulfonates and carboxylates of (E) -3- (hydroxymethyl) -5-methyldihydro-2 (3H). -furanone of formula I, OX where X represents acetyl, mono- to trichloroacetyl, mono- to tribromoacetyl, trifluoroacetyl, propionyl, butyroyl, isobutyroyl, cyclohexanecarbonyl, 1-adamantanecarbonyl, benzoyl ', 4-nitrobenzoyl, 4-fluorobenzoyl, 4-chlorobenzyl, 4-bromobenzoyl, 4-bromobenzenzyl , methanesulfonyl, trifluoromethanesulfonyl, benzenesulfonyl, 4-toluenesulfonyl, 4-bromobenzenesulfonyl, 1-naphthalenesulfonyl or 2-naphthalenesulfonyl, characterized in that the sodium salt of 3- (hydroxymethylene) -5-methyldihydro-2 (3H) -furanone is treated with carboxylic chloride or the sulfonic acids of formula II, X-Cl (II) wherein X is as defined for compounds of formula I, or a carboxylic acid or sulfonic acid bromide of formula III, X-Br. (III) wherein X is as defined for compounds of formula (I), or a carboxylic or sulfonic anhydride of formula (IV), (X ₂ JO (IV)) wherein X is as defined for compounds of formula (I) , such as triethylamine, trimethylamine, pyridine or quinoline, at room temperature.