Thiophene, phosphorus substituted

In this review, synthesis, structure, and redox properties of phosphaquinoid compounds are described, keeping the contribution of thienoquinoid structures in mind in the first part. In the second part, synthesis and structure of phosphorus substituted thiophene and related compounds, especially tetraphosphoryl derivatives, are outlined (Scheme 3). 

Phosphorus pentachloride at 180°C converted benzoxazole, substituted at C-2 by 3,4-dihydroxy-2-(p-nitrophenyl)thiophene, into the 3,4-dichlorinated thiophene derivative only (91JHC1449). 

Reaction of the 2-amino-substituted thiophene 244 with pyrrolidinone in the presence of phosphorus oxychloride led to efficient formation of the central six-membered ring of tricycle 245 in 57% yield (Equation 67)... 

Unsubstituted thienothiophenes 1 and 2 are smoothly formylated in the 2-positions by DMF-phosphorus oxychloride in dchloro-ethane. The site of substitution in thienothiophene 2 was confirmed by preparing the corresponding formyl derivative from 2-lithiothieno-[3,2-6]thiophene and DMF, and in the case of 1, by oxidizing the formyl derivative to thieno[2,3-h]thiophene-2-carboxylic acid, as well as the NMR spectra [Eqs. (66) and (67)]. 

This synthesis of benzo[6]thiophenes is probably the most widely exploited single method for such syntheses since its introduction about 1950 by a variety of workers. It is applicable to a great number of highly substituted benzo[6]thiophenes, and intermediates are generally readily available. In 1949 Werner (49RTC509) reported the synthesis of several 3-alkyl- and 2,3-dialkyl-benzo[( ]thiophenes by cyclodehydration of arylthioacetones (99) with phosphorus pentoxide or anhydrous zinc chloride. Arylthioacetaldehydes (99 R = H, R1=H, R2 = Me, Et or Ph) have been cyclized in 65-80% yields with phosphorus pentoxide. In 1950 Tilak (50PIA(A)(32)390) introduced the polyphosphoric acid-promoted cyclization of... 

Substituted hexynediols such as (309) reacted with sulfur/phosphorus trisulfide to yield thieno[3,2-6]thiophene derivative (310 Scheme 106). The reactions described above, however, are not of practical use (76AHC(19)123). 

In 1949, Werner187 announced the synthesis of several 3-alkyl- and 2,3-dialkylbenzo[6]thiophenes by the cyclodehydration of (arylthio)-acetones with phosphorus pentoxide or zinc chloride [Eq. (5)]. The reaction has since been widely used to synthesize alkyl- and aryl-substituted benzo[6]thiophenes (Table IV). Cyclodehydration proceeds most conveniently with PPA,297 298 but concentrated sulfuric acid,299,300 hydrofluoric acid, 299 aluminum chloride in benzene301 or chlorobenzene,302 zinc chloride and hydrochloric acid,303 a melt of aluminum and sodium chlorides,304 and phosphorus pentoxide in boiling o-dichlorobenzene 305 have been less widely used. 

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... 

Tetrahydrobenzo[ ]thiophene behaves like thiophene in electrophilic substitution reactions. Thus, it is formylated with a mixture of vV-methylformanilide and phosphorus oxychloride,436 iodinated in the presence of mercuric oxide,193 and brominated by V-bromosuccinimide,193 all in the 2-position in Friedel-Crafts reactions with acetyl chloride,194-436 propionyl chloride,436 succinic... 

The azlactone formed from benzo[6]thiophene-2-carboxaldehyde and hippuric acid reacts with hydriodic acid and red phosphorus to give a-amino-/9-(2-benzo[6]tbienyl)propionic acid, and with sodium hydroxide to give a-benzamido-j8-(2-benzo[6]thienyl)acrylic acid.477 A series of a-amino-j8-(5-substituted-3-benzo[6]thienyl)propionic acids (312 R = H) has been prepared by hydrolysis of the product of... 

The Vilsmeier-Haack reaction (herein, Vilsmeier reaction ) provides an effective method for the formylation of aromatic systems. The combination of phosphoryl chloride with V-methylaniline or dimethylformamide generates an iminium phosphorus derivative or chloro-iminium cation that is the active electrophile in an electrophilic substitution reaction. The resulting substitution product is an iminium salt 1, which is hydrolyzed on workup with alkali to give the carbaldehyde product 2 (Scheme l).1,2 The method is particularly useful with activated arenes or electron-rich heterocycles, such as pyrroles, furans, thiophenes, and indoles. We had a special interest in the preparation of indole-7-carbal-dehydes, namely, their properties as isosteres of salicylaldehyde. Thus, we became involved in a wide-ranging investigation of 4,6-dimethoxy-... 

The [4+1] cycloadducts formed from 4,4-bis(trifluoromethyl)-l-oxa-buta-1,3-dienes (92JPR219) and tin(II )-chloride are transformed on heating into 4,4-difluoro-3-trifluoromethylbut-3-en-l-ones, which on treatment with sodium hydride yield 2-fluoro-3-trifluoromethylfurans (92CC348). When heated with phosphorus pentasulfide, l-aryl-4,4-difluoro-3-trifluor-omethylbut-3-en-l-ones give 2-fluoro-3-trifluoromethylthiophenes. The fluorine atom at C—2 of the furans and thiophenes can readily be substituted by a wide variety of nucleophiles (92JPR3II). This reaction sequence represents a preparatively useful method for the selective introduction of biologically relevant substituents into the C—2 position of 3-trifluoro-methyl-substituted furans and thiophenes (Scheme 87). 

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