Arylthio cyclization

The cyclization of 5-hydrazine-6-arylthio[l,2,4[triazin-3(2//)-ones 849 was effected by formic acid to give 950 (74MIP1). They are potentially useful as antibacterial, antiviral, and antimetabolic agents. Cyclization of... 

Dibenzo[/>,/]thiepin derivative (39) has been obtained by cyclization of 2-arylthio-5-nitrophenylpyruvic acid (38) in the presence of polyphosphoric acid 33>. The use of this Friedel-Crafts type reaction is restricted to the synthesis of the stable di- and tri-annelated thiepins such as 40 33), 41 7), and 42 34). 

The 1-benzothiopyrylium salts are best prepared from the easily accessible thiochroman-4-one [Eq. (35)].6,51,52,302-304 The common dehydrating agents include potassium hydrogen sulfate8 and phosphorus pentoxide51,302-304while sulfuryl chloride/perchloric acid51,302-304 and trityl perchlorate 6 have been useful as hydride extractors. Another method involves the cyclization of /1-ketosulfides (e.g., 81) or j8-arylthio-acroleins (82) with perchloric acid [Eq. (36)].305,306... 

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). 

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). 

A variety of substituted 3-aminobenzo[6]thiophenes have been obtained by ring closure reactions of nitriles (equation 57). Various o -cyanophenylthioacetyl derivatives, when treated with base, yield the 3-amino derivatives (Section 3.15.2.2.3). The benzonitriles may be obtained by displacement of the o-nitro group from o -nitrobenzonitriles (74JOC3440). 2-Arylthio-l-chloroenamines are cyclized to 3 -dialkylaminobenzo[6]thiophenes in the presence of Lewis acid catalysts (equation 58). The 1 -chloroenamines may be prepared from t-amides or ynamines <8lH(15)l 179>. 

The synthesis of benzo[6]thiophenes by the PPA-promoted cyclization of (arylthio)acetaldehyde dimethyl or diethyl acetals [Eq. (4)] was introduced by Tilak287, 288 in 1950 and improved in 1951.289 The acetals are readily prepared from aryl mercaptans and bromo-acetaldehyde dimethyl (or diethyl) acetal in the presence of sodium ethoxide, or by reaction of an aryllithium compound with [(MeO)2CHCH2S]2.290 Diethyl acetal as starting material sometimes gives better yields of product than the corresponding dimethyl acetal.291 Optimum yields of benzo[6]thiophenes are obtained when cyclization of the acetals is carried out under reduced pressure so that the lower boiling benzo[6]thiophenes distill as soon as they are formed. Experimental conditions for obtaining optimum yields vary from case... 

Stannic chloride has been used successfully to cyclize a few (arylthio)acetaldehyde diethyl acetals.291... 

C. Cyclization op (Arylthio)acetones and Aryl Phenacyl Sulfides... 

Cyclodehydrations of ortho- or para-substituted (arylthio)acetones afford 7- and 5-substituted 3-methylbenzo[6]thiophenes,respectively mete-substituted (arylthio)acetones afford mixtures of 4- and 6-substituted 3-methylbenzo[6]thiophenes (see, e.g., Matsuki and Ito105). However, in these cases a partial migration of the 3-methyl group to the 2-position may be an added complication.297,306 Such isomerizations occur during the preparation of 3-methylbenzo[6]thio-phene and its 5-alkyl,297 306 but not its 5-halo 297 derivatives. A mixture of 3-methylbenzo[6]thiophene and its 5- (the expected product) and 6-JerJ-butyl derivatives is obtained on cyclization of (p-terf-butyl-... 

Cyclization of the (arylthio)acetaldehydes PhSCHRCHO (R = Me, Et, or Ph) with phosphorus pentoxide gives the corresponding 2-substituted benzo[6]thiophene in 65-80% yield.314... 

The second example is photochemical reaction of 2-benzoylbenzothioesters 57 in the chiral crystalline environment. Solid-state photoreactions of, S -(o-tolyl),. S -phcnyl, and S-(ff)-tolyl) 2-benzoylbenzothioates 57a-c, which formed chiral crystals by spontaneous resolution, underwent an intramolecular cyclization involving phenyl migration to afford the corresponding optically active 3-phenyl-3-(arylthio)phthalide 58a-c in good chemo- and enantio-selectivities. (Scheme 11). [34]... 

Sulfoxide elimination of the arylthio group of 5, deprotection of the silylacetylene (KF), acetal hydrolysis (CSA in CH3CN-H20), and silylation of the free hydroxyl group provides the aldehyde 6 in 80% overall yield from 5. On treatment with LiN[Si(CH3)3]2 and CeCl3 (3 equiv.) in THF at 0°, 6 cyclizes to 7, obtained as a... 

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