Methyl phenyl sulfone, preparation from

The dipolarophile was prepared in a short (three-step) sequence from methyl phenyl sulfone (38% overall yield) and ethyl trifluoroacetate. Desulfonation, followed by reductive N-0 cleavage afforded the syn aminoalcohols [246]. Conjugate additions to the sulfone were described some years earlier [247] more recently, trifluoromethyl pyrroles have been synthesised from the nitro-propene [248]. 

The presence of an NH group is essential, since the Boc-p-amino sulfone derived from Pro could only be coupled with lower yields (-20%). This method is also suitable for the preparation of pseudodipeptides having functionalized side chains such as those of Ser and AsnJ72l The p-oxo sulfone 51, which was obtained by reacting Boc-pAla-OMe with the dilithium anion of methyl phenyl sulfone, cleanly reacted with ethyl bromoacetate to give the p-oxo sulfone 52 (86%). The latter was reduced using LLAIH4, which on reductive elimination produced the over-reduced Boc-Alai)i(CH2—CH2]Gly-OMe isostere (80%). 

Mixed homocuprates.7 Mixed cuprates (1) in which the nontransferable ligand is an a-sulfonyl carbanion are easily prepared from dimethyl sulfone or methyl phenyl sulfone (equation I), and are effective for conjugate addition to enones and for a synthesis of ketones from acid chlorides. 

After the mixture is cooled to 75°, 200 ml. of benzene is added (Note 5). The mixture is stirred briefly, and the liquid is decanted from the solid into a 5-1. separatory funnel. The aqueous layer is separated and extracted again with 200 ml. of benzene. The aqueous layer is then returned to the separatory funnel, and the solid in the reaction flask is washed in with it by means of 2 1. of water. The mixture is shaken with 200-ml. portions of benzene until all solid has dissolved (usually three portions of benzene suffice). All the benzene extracts are combined and dried with 20 g. of anhydrous calcium chloride. The drying agent is removed by filtration and washed with two 20-ml. portions of benzene. Benzene is removed from the filtrate by distillation under reduced pressure (Note 6), and the solid which separates is dried further at about 10 mm. and room temperature to constant weight. The yield (Note 2) of methyl -tolyl sulfone is 298-317 g. (69-73%), m.p. 83-87.5°. Further purification is generally unnecessary, but, if desired, the product may be recrystallized from carbon tetrachloride or ethanol-water (1 1). The submitters state that the method may be extended to the preparation of methyl phenyl sulfone and, presumably, of methyl aryl sulfones generally (Note 7). 

Treatment of the epoxy sulfones obtained thus with MgBr2 produces a-bromo ketones or a-bromo al-dehyde. This conversion can be applied to stereoselective preparations of a-bromo methyl ketones from cyclohexanone derivatives. Thus, treatment of 17-P-hydroxy-5-a-androstan-3-one (134) with 1-chloroethyl phenyl sulfone provides an epoxy sulfone (135), which is cleaved by MgBr2 to give a 99 1 mixture of 3-acetyl-3-bromoandrostanes (136 and 137 equation 33), whereas similar treatment of 17-p-hydroxy-5-B-androstan-3-one (138) gives a 4 96 mixture of 3-acetyl-3-bromoandrostanes (139 and 140 equation 34). These facts may reflect the steric course of the initial attack of the a-sulfonyl carbanion on the carbonyl face. 

A-Alkylpyridinium salts 20 with alkyl chains from 14 to 22 carbon atoms andp substituents such as methyl, phenyl, and styryl groups (stilbazolium salts) with Cl", Br", I", BPh ", and C H SOj" counteranions were prepared by Ster et al. [27]. The stability of the SmA phase increased with the size of the anion, but no mesophase was observed with heptyl sulfonate. 

One Sanofi synthesis of enantiomerically pure (-i-)-clopidogrel (2) utilized optically pure (R)-(2-chloro-phenyl)-hydroxy-acetic acid (20), a mandelic acid derivative, available from a chiral pool. After formation of methyl ester 21, tosylation of (/ )-21 using toluene sulfonyl chloride led to a-tolenesulfonate ester 22. Subsequently, the Sn2 displacement of 22 with thieno[3,2-c]pyridine (8) then constructed (-i-)-clopidogrel (2). Another Sanofi synthesis of enantiomerically pure (-i-)-clopidogrel (2) took advantage of resolution of racemic a-amino acid 23 to access (S)-23. The methyl ester 24 was prepared by treatment of (S)-23 with thionyl chloride and methanol. Subsequent Sn2 displacement of (2-thienyl)-ethyl para-toluene-sulfonate (25) assembled amine 26. 

Dimethyl-2-phenyl-3,4-pyrazolidinedione and its 1,5-diphenyI-2-methyl analog are the only compounds of their class known. The former has been synthesized by treatment of l-(2,3-dioxobutyryl)-l-phenyl-2-methyl-2-nitrosohydrazine hydrate with sodium bisulfite" and by methylation of 4-hydroxy-3-methyl-l-phenyl-2-pyrazolin-5-one.820 The latter compound has been prepared in the same way.1243 The dimethyl phenyl compound has also been isolated from urine as a metabolic product of 4-dimethylamino-2,3-dimethyl-l-phenyl-3-pyra-zolin-5-one617 and it is formed by treatment of the same compound with sulfuric acid.618 The 4-thiono analog is also known. Reduction of 2-3-dimethyl-l-phenyl-5-oxo-3-pyrazolin-4-sulfonic acid using zinc in acid gives l,5-dimethyl-2-phenyl-4-thiono-3-pyrazolidinone.1249... 

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