2-arylthio-ketones

Alkyl- or aryl-dibenzothiophenes are conveniently prepared from the 2-arylthio-cyclohexanones, which are readily cyclized and dehydrogenated to yield the respective 1-, 2-, 3- or 4-substituted dibenzothiophenes (382 equation 9 Section 3.15.2.3.2). More complex polycyclic systems are available, using suitable aryenethiols, such as naph-thalenethiols, and 2-bromo-l-tetralone to synthesize the appropriate 2-arylthio ketones. Diaryl sulfides can be converted to dibenzothiophene derivatives in satisfactory yields by photolysis in the presence of iodine (equation 10) (75S532). Several alkyldibenzothiophenes with substituents in the 2- and/or 3-positions were prepared in satisfactory yield by the condensation of dichloromethyl methyl ether with substituted allylbenzo[6]thiophenes (equation 11) (74JCS(P1)1744). 

Benzothiophenes are biologically important molecules that exhibit anti allergenic, and ocular hypotensive properties, and prevent osteoporosis. Kim and coworkers have shown that BE3 OEt2 is efficient in mediating the Eriedel-Craft type cyclization of 2-arylthio-ketones (43) at ambient temperature to give the 3-aryl-substituted benzothiophenes (44) in good yields (Equation 29) [31]. 

S-Alkylation of thiols by carbene complexes can be a useful approach to a-(alkylthio)- or a-(arylthio)ketones, although few examples of intramolecular [975,1193] or intermolecular [497,1043,1230-1233] S-H bond insertion reactions of electrophilic carbene complexes have been reported. Yields are sometimes low, probably because of the poisoning of the catalyst by the thiol. Examples are given in Table 4.15. 

Comparable acid- (or Lewis acid) -catalysed ring closures of 2-arylthio- and 2-aryloxy- -ketones, and -2-arylthio- and 2-aryloxyacetyl- chlorides lead to 3-substituted heterocycles and 3-oxygenated heterocycles, respectively. It is possible to combine the preparation of the arylthio-ketone and the ring closure steps utilising two solid-supported reagents in a one-pot procedure, as illustrated. Formation of 3-aryl-benzothiophenes by this route can be complicated by partial or complete isomerisation to the 2-aryl-heterocycle,however using boron trifluoride as the Lewis acid produces only the 3-aryl-isomer. 3-Tosylamino-benzofurans can be prepared from aryl glyoxal hydrates. ... 

In 1951-1953 Rabindran and Tilak51,52 introduced a new dibenzo-thiophene synthesis and extended it to tetracyclic and pentacyclic systems. This method involves a two-step process of condensing a thioarenol with an a-halo ketone or a-haloacetal to form an a-(arylthio) ketone or a-(arylthio)-acetal intermediate, which is subsequently cyclized intramolecularly. The three principal variations introduced by Tilak and co-workers are presented in Schemes 3, 5, and 6 and were summarized in I960.528... 

Quinine-molybdenyl acetoacetonate p-(Arylthio)ketones from p-aminoketones Kinetic resolution... 

The Takemoto s catalyst (9) was extensively employed for the enantioselective addition of arylthiols to a,P-unsaturated carbonyl compounds and P-arylthio ketones were obtained in good ees [90]. Conjugate addition of thioacetic acid to nitroalkene and to enone have been also reported by Wang [91]. 

The nature of the arylthio substituent at C-4 of a 5(277)-oxazolone dictates which of two different synthetic strategies can be used. The first involves the use of sodium cyanodithioformate and the corresponding ketone as starting materials. The reaction occurs through a thiazolone 45 that must be alkylated on the sulfur atom followed by treatment with Hg(OAc)2 to afford the corresponding 4-(alkylthio)-5(2//)-oxazolone 47. The second strategy involves the addition of thiophenol to... 

TABLE 7.6 SYNTHESIS OF 4-(ARYLTHIO)-5(2H)-OXAZOLONES FROM ETHYLCYANOFOR-MATE, KETONES AND ARYLTHIOLS, 141... 

Disubstituted furans (130) can be obtained by treatment of j8-alkoxy- and j8-arylthio-a,j8-unsaturated ketones, for example 3-methoxy-l-phenyI-2-buten-l-one (128) or 3-ethylthio-l-phenyl-2-buten-l-one (129), with dimethylsulfonium methylide (79JHC815, 69TL679). The possible reaction pathway (Scheme 27) shows the initially formed epoxides as rearranging by ring opening at the tertiary epoxide carbon atom. 

While ortho- or para -substituted arylthio methyl ketones form 7- or 5-substituted benzo[6 ]thiophenes, respectively, meta -substituted arylthio methyl ketones give mixtures of 4- and 6-substituted benzo[6 ]thiophenes. The relative amounts of these isomers depend on the nature of the substituent to some extent. Cyclization of the pyruvic acid derivative... 

Ring-closure techniques are more commonly used to obtain 3-alkylbenzo[6]thiophenes. Thus, acid-catalyzed cyclization of arylthio methyl ketones gives the 3-alkylbenzo[6]thio-phenes in good yield, with little rearrangement (equation 3). Formation of the 3-aryl-benzo[6]thiophenes by this approach is complicated, however, by rearrangement to the 2-isomer (Section 3.15.2.3.2). 3-Methylbenzo[f> Jthiophene is also obtained by decarboxylation of the corresponding 2-carboxylic acid (equation 4), readily available from ar-mer-captocinnamic acids (Section 3.15.2.1.1). 

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