2- Chloro-4-phenyl thiophene

Radicaloid substitution has not been extensively studied in the thiophene series. Molecular orbital calculations indicate that substitution should occur in the a-position. This has been found to be the case in the Gomberg-Bachmann coupling of diazohydroxides with thiophenes which has been used for the preparation of 2-(o-nitro-phenyl) thiophene, 2-(p-toluyl) thiophene, " " and 2-(p-chloro-phenyl)thiophene. " Coupling in the /8-position has been used for the preparation of 1,3-dimethyl-4,5-benzisothionaphthene (148) from 2-amino-tt-(2,5-dimethyl-3-thienyl)cinnamic acid (149). A recent investigation describes the homolytic phenylation of 2- and 3-phenyl-... 

There is an early report that thiophene reacts at the 3-position in phenylation with benzenediazonium chloride and aluminum trichloride, but in the Gomberg reaction thiophene has been found to substitute mainly at the 2-position both with p-tolyl and with p-chloro-phenyl radicals.Bcnzothiazole is phenylated at the 2-position in low yield by dibenzoyl peroxide a small quantity of the 4-isomcr is also obtained. ... 

During the development of rivaroxaban 1, Pleiss et al. at Bayer Health Care prepared [14C]-radiolabeled rivaroxaban,22 which was required for clinical studies of drug absorption, distribution, metabolism, and excretion (ADME studies). The approach taken for the synthesis of l4C labeled rivaroxaban 38 relies on the previously reported synthesis. In the presence of EDC HCl and HOBT, 4- 4-[5S)-5-(aminomethyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl -morpholin-3-one 22 was coupled with 5-chloro-2-thiophene [14C]-carboxylic acid 37 and was purified using chiral HPLC to afford the [l4C]-radiolabelled rivaroxaban 38 in 85% yield with high chemical and radiochemical purity and with an enantiomeric excess of > 99% ee (Scheme 5). Meanwhile, the metabolite M-4 of rivaroxaban (compound 39) was prepared from 5-chlorothiophenecarboxylic acid chloride 23 and [14C]glycine in 77% yield (Scheme 6). 

Benzo[b]thiophene, 3-chloro-2-phenyl-synthesis, 4, 116 Benzo[6]thiophene, 2-cyano-synthesis, 4, 921 Benzo[6]thiophene, 3-cyano-synthesis, 4, 922... 

Further research on the substitution of the thiophene 3-position with phenyl groups containing electron-withdrawing or electron-donating groups (such as methyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, sulfoxy) in the para position have lead to polymers with unique features [57]. The electron-withdraw-ing groups allow the formation of a radical anion and thus stabilize the n-doped state. As a result, such conducting polymers can be reversibly oxidized and reduced and electrochromic devices can be built with identical anode and cathode materials [58]. 

Treatment of 3-chloro-2-phenylbenzo[ ]thiophene with -butyllithium, followed by quenching with NH4C1, gave a 71% yield of the l-phenyl-2-(2- -butylthiophenyl)acetylene, which is obviously the result of nucleophilic attack at the sulfur with cleavage of the ring and elimination of chloride. 

Preparation of thiophene-2-carboxylic acid (2- 3-[3-(4-chloro-phenoxy)-pyrrolidin-l-yl]-2-hydroxy-propoxy -phenyl)-amide... 

Preparation of Acid l-(2-Methyl-5-Chloro-Thiophen-3-yl)-2-(2-Methyl-5-Hydroxycarboxy-Thiophen-3-yl)Cyclopentyl-3,6-Epoxy-4-Cyclohexene-l,2-Dicarboximide exo-A-(4-Phenylate)... 

During the preparation of l-chloro-l-(2-furyl)cyclopropanes a small amount (up to 12%) of 5-tert-butoxy-2-chloromethylene-2,5-dihydrofuran, the addition product of potassium tert-butoxide to the bipolar structure of chloro(2-furyl)carbene, was formed.Cyclopropanes substituted at C 3 in the thiophene ring are sometimes unstable to column chromatography. The sterically more crowded chloro(3-phenyl-2-thienyl)carbene failed to undergo addition to 2,3-dimethylbut-2-ene. ... 

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