Acyl-thiophenes

Acyl peroxides Acyl thiophenes Adalat Adamantane Adamantane [281-23-2]... 

Fatty acids are prepared by acylating thiophene with acid chlorides and reducing the ketones (218) to alkylthiophenes according to Wolff-Kishner or Clemmensen. The latter are then acetylated and oxidized by hypochlorite to 5-alkyl-2-thiophenecarboxylic acids, > ... 

In glatter Reaktion werden Formyl- bzw. Acyl-thiophene mit Triathyl-siliciumhydrid in Trifluoressigsaure zu Alkyl-tetrahydro-thiophenen reduziert (s, S. 99). 

Microwave irradiation has been used to accelerate the Gewald reaction for the one-pot synthesis of N-acyl aminothiophenes on solid support [67]. A suspension of cyanoacetic acid Wang resin 35, elemental sulfur, DBU and an aldehyde or ketone 36 in toluene was irradiated for 20 min at 120 °C in a single-mode microwave synthesizer (Scheme 13). Acyl chloride 37 was added, followed by DIPEA, and the mixture was irradiated for 10 min at 100 °C. After cooling to room temperature, the washed resin was treated with a TEA solution to give M-acylated thiophenes 38 in 81-99% yield and purities ranging from 46-99%. 

A similar product, 469, is formed when the acylated thiophene 468 is heated with KSCN in EtOH (Equation 174) <2000H(53)2363>. 

Another interesting multi-component reaction is the Gewald synthesis leading to 2-amino-3-acyl thiophenes (Scheme 7.25), which are of current interest since they are commercially used as dyes, conducting polymers and have shown extensive potential for pharmaceutical purposes. 

The ruthenium-catalyzed addition of C-H bonds in aromatic ketones to olefins can be applied to a variety of ketones, for example acetophenones, naphthyl ketones, and heteroaromatic ketones. Representative examples are shown in the Table 1. Terminal olefins such as vinylsilanes, allylsilanes, styrenes, tert-butylethy-lene, and 1-hexene are applicable to this C-H/olefin coupling reaction. Some internal olefins, for example cyclopentene and norbornene are effective in this alkylation. The reaction of 2-acetonaphthone 1 provides the 1-alkylation product 2 selectively. Alkylations of heteroaromatic ketones such as acyl thiophenes 3, acyl furans, and acyl pyrroles proceed with high yields. In the reaction of di- and tri-substitued aromatic ketones such as 4, which have two different ortho positions, C-C bond formation occurs at the less congested ortho position. Interestingly, in the reaction of m-methoxy- and m-fluoroacetophenones C-C bond formation occurs at the congested ortho position (2 -position). 

Acetylthiophene reacts with synthesis gas to give 2-ethylthiophene. If the reaction is carried to completion, 2-ethylthiacyclopentane is secured. Acylated thiophenes are readily secured by the Friedel-Crafts reaction and their hydrogenation by hydrogen-carbon monoxide mixtures opens up a new synthetic route to the alkylthiophenes. and their tetra-hydro analogs. The evidence seems to indicate that the conversion of a substituted thiophene to the reduced thiacyclopentane is a stepwise process which with 2-thiophenecarboxyaldehyde may be represented as follows ... 

Sodium/ammonia" treatment also causes disruption of the ring in thiophene and simple thiophenes, however thiophene-2-carboxylic acid and 2-acyl-thiophenes can be converted into the 2,5-dihydro derivatives using lithium in ammonia, followed by protonation or trapping with an alkyl halide."" Side-chain reductions can be carried out with metal hydrides, which do not affect the ring. 

Winter M., Gautschi F., Flament I., Stoll M. and Goldman I.M. (Firmenich Cie) (1976b) Flavoring agents acyl thiophenes. US Patent 4000328. 

Dealuminated HY zeolites have been shown to be efficient catalysts for the selective preparation of 2-acyl thiophenes in the reaction nf thiophene with various acyl chlorides. The acylation reaction of thiophene with butyroyl chloride over HY (Si/Al =15) zeolite, in chlorobenzene as solvent, follows a Langmuir-Hinshelwood kinetic law, which involves the adsorption of the two reactants on identical sites of the catalyst surface. ... 

Cantrell has reported the photoaddition reactions of tetramethylethylene and isobutene to 2-acyl-thiophens, -furans, and -pyrroles.42 Products of both [4 + 2]- and [2 + 2]-addition to the ring and oxetan formation are observed in amounts dependent upon the olefin, the particular five-membered heteroaromatic compound, and its acyl substituent, e.g. 2-acetylthiophen with tetramethylethylene yields the [4 + 2]Diels-Alder adduct as the major product, with minor amounts of the [2 + 2]cyclobutane adduct and the oxetan, whereas isobutene gives the two isomers of the [4 + 2]product and the oxetan. 

Hoener et al. [90] investigated a one-pot reaction for Gewald synthesis on solid support (Scheme 11.37). The products 2-amino-3 acyl thiophenes are used commercially as dyes. 

Scheme 78 The reaction of a 1,3-diketone enolate with carbon disulfide leading to a 2-methylthio-3-acyl thiophene [126]...

The addition of the enolate of a 1,3-diketone to carbon disulfide generates a dianion, e.g. 55, which, following two successive S-alkylations, can produce 2-methylthio-3-acyl thiophenes 56. The first alkylation requires a 2-halo-carbonyl compound (a 2-halo-ketone in the example in Scheme 78) to allow the ring closure via an intramolecular aldol condensation and then a second with iodomethane to complete the sequence [126]. 

Scheme 44 Synthesis of 4-chloromethyl dmvatives of 2-acyl thiophenes [62]...

Smutny. The t-butyl ester was used in order to achieve hydrolysis of (30), which required reaction with trifluoroacetic acid at 0 °C for 4—5 h. Treatment of (30) with warm trifluoroacetic acid for 10 min yielded (31). The reaction of (29) with ethyl a-chloroacetate gave (32). A-Phenyl phenylpropynthioamide (33) reacts in a similar manner with active bromomethylene derivatives, such as bromo-acetonitrile, bromonitromethane, and /j-nitrobenzyl bromide, in the presence of triethylamine to give the thiophen (33a). Instead of enamine thioesters such as (29), 2-aminovinyl thioketones (34) react with a-bromo-ketones in the presence of triethylamine to give 2-acyl-thiophens (35). By the ion-pair extraction method, tetrabutylammonium salts of acetylacetone were allowed to react with carbon disulphide to give (36), which upon reaction with chloroacetone gave a 45% yield of the thiol (37), in addition to a thieno[2,3-A]thiophen derivative. ... 

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