JP2002541101A5 - - Google Patents

Description

(E) -Styryl and benzylsulfones are prepared by Knebena gel condensation of aromatic aldehydes with active methylene molecules such as aryl, benzyl, styrylsulfonylacetates, phenacylarylsulfones and sulfonylacetoacetate. The procedure is described in Reddy et al. [Lady et al . , Acta. Chim. Hung. 115: 269 (1984); Lady et al., Sulfur Letters 13:83 (1991); Lady et al., Synthesis 322 (1984); Sulfur Letters 7:43 (1987)]. The entire disclosures of which are incorporated herein by reference. (Z) -benzyl and (Z) -styryl sulfones are synthesized by nucleophilic addition of aromatic and aliphatic thiols to phenylacetylene, followed by oxidation of the product with 30% hydrogen peroxide.

Preparation of benzylsulfonyl and arylsulfonylacetic acids Aryl and benzylsulfonylacetic acids are starting compounds for the synthesis of (E) -styrylaryl and (E) -styrylbenzylsulfones. Arylsulfonylacetic acids can be prepared by the condensation of sodium arylsulfinate and chloroacetic acid at alkaline pH. An alternative method of synthesizing these compounds involves oxidizing the product obtained by condensation of sodium arylthiolate with chloroacetic acid.

Synthesis of (E) -styrylaryl and (E) -benzylsulfones To prepare (E) -styrylbenzyl and (E) -styrylbenzylsulfones, a suitable sulfonylacetic acid (for example, 10 mmol), an aromatic aldehyde A mixture of (eg, 10 mmol) and a catalytic amount of benzylamine (eg, 15 ml) in acetic acid was refluxed for 2-3 hours. After cooling, dehydrated ether (dry ether) was added and the reaction mixture was cooled overnight. The ether solution is washed successively with sodium bicarbonate, a saturated solution of sodium bisulfite (bisulfite), dilute hydrochloric acid and finally with water. Evaporation of the sodium sulfate dehydrated ether solution gives a solid product of (E) -styrylaryl or benzylsulfones, which can be recrystallized with 2-propanol or 95% ethanol.

Synthesis of (Z) -styrylaryl and (Z) -styrylbenzylsulfones (Z) -styrylaryl and (Z) -styrylbenzylsulfones are prepared from a suitable thiol (eg, 10 mmol) and sodium hydroxide (eg, 20 mmol). The prepared sodium aryl thiolate or benzyl thiolate can be prepared by adding to freshly distilled phenylacetylene in methanol. The mixture is refluxed for 24 hours and poured on crushed ice. The (Z) -styrylaryl and (Z) -styrylbenzyl sulfides are oxidized with 30% hydrogen peroxide to give (Z) -styrylaryl and (Z) -styrylbenzylsulfones, respectively.

Step 1
General Procedure for the Synthesis of Styryl and Benzyl Aryl Sulfones To a solution of sodium hydroxide (8 g, 0.2 mol) in methanol (200 ml) is added slowly the appropriate thiophenol or benzyl mercaptan (0.1 mol). Thereafter, chloroacetic acid (0.1 mol) is added to each portion and the reaction mixture is refluxed for 2-3 hours. The cooled contents are poured on crushed ice and neutralized with dilute hydrochloric acid (200 ml). The resulting aryl and benzylthioacetic acids (0.1 mol) are oxidized with 30% hydrogen peroxide (0.12 mol) in glacial acetic acid (25 ml) by refluxing for 1-2 hours. After cooling the contents, pour onto crushed ice. The separated solid is recrystallized from hot (hot) water to give pure aryl and benzylsulfonylacetic acids.

  Reflux the appropriate aryl or benzylsulfonylacetic acid (0.001 mol), aromatic aldehyde (0.001 mol) and benzylamine (1 ml) in glacial acetic acid (15 ml) for 2-3 hours. Cool the contents and treat with dry ether (50 ml). Any separated product is collected by filtration. The filtrate is diluted with further ether and washed successively with sodium bicarbonate (20 ml), a saturated solution of sodium bisulfite (bisulfite) (20 ml), dilute hydrochloric acid (20 ml) and finally with water (35 ml). Evaporation of the dehydrated ether layer often gives a solid. However, in some cases, it may give a syrupy substance isolate, which solidifies upon treatment with 2-propanol. The purity of these compounds was confirmed by TLC (silica gel BDH, hexane / ethyl acetate 3: 1).

Step 3
General Procedure for the Synthesis of 2- (arylsulfonyl) -1-phenyl-3-aryl-2-propen-1-ones These compounds are prepared by two methods employing different reaction conditions, solvents and catalysts. Synthesized.

  Method 1: Phenacyl aryl sulfones are made by refluxing α-bromoacetophenones (0.05 mol) and sodium arylsulfinates (0.05 mol) in absolute ethanol (200 ml) for 6-8 hours. . The product separated by cooling is filtered and washed several times with water to remove sodium bromide. Thereafter, the product is recrystallized from ethanol: phenacyl-phenylsulfone, m.p. p. 90-91 ° C; phenacyl-p-fluorophenylsulfone, m.p. p. 148-149 ° C; phenacyl-p-bromophenylsulfone, m.p. p. 121-122 ° C; phenacyl-p-methoxyphenylsulfone, m.p. p. 104-105 ° C; p-nitrophenacyl-phenylsulfone, m.p. p. 136-137 ° C.

A solution of phenacylarylsulfone (0.01 mol) in acetic acid (10 ml) is mixed with alaldehyde (0.01 mol) and benzylamine (0.02 ml) and refluxed for 3 hours. The solution is cooled and dry ether (50 ml) is added. The ether solution is washed successively with dilute hydrochloric acid, aqueous 10% NaOH, saturated NaHSO ₃ solution and water. Evaporation of the dehydrated ether layer gives a solid product, which is purified by recrystallization.

  Method 2: Dehydrated tetrahydrofuran (200 ml) is placed in a 500 ml conical flask flushed with nitrogen. To this is added dropwise titanium (IV) chloride (11 ml, 0.01 mol) in anhydrous carbon tetrachloride with continuous stirring. The contents of the flask are maintained at −20 ° C. throughout this addition process. A mixture of phenacyl aryl sulfone (0.01 mol) and aromatic aldehyde (0.01 mol) is added to the reaction mixture, and pyridine (4 ml, 0.04 mol) in tetrahydrofuran (8 ml) is slowly added over 1 hour. Stir the contents for 10-12 hours, treat with water (50 ml), then add ether (50 ml). The ether layer is separated and washed with 15 ml of a saturated solution of 10% sodium hydroxide, sodium bisulfite (bisulfite) and brine (brine). The dehydrated ether layer is evaporated to give 2- (arylsulfonyl) -1-phenyl-3-aryl-2-propen-1-ones.