Thiophenes, acylation nitration

Friedel-Crafts acylation, nitration, sulfonation, and bromination of benzo[ )naphtho[l,2-d]thio-phene take place at the position shown in (369) <84PJCI243>. Nitration as well as Friedel-Crafts acetylation of phenanthro[4,5-Z>c. 

It is thus apparent that the selectivity of a reagent toward thiophene and benzene can differ appreciably, and this difference in selectivity is also strongly noticeable in the proportions of 2- and 3-isomers formed. Although in certain reactions no 3-isomer has been detected, appreciable amounts have been found in other reactions. Thus 0.3% of the 3-isomer has been found in the chlorination of thiophene.- Earlier results indicated that 5-10% 3-nitrothiophene is formed in the nitration of thiophene and a recent gas-chromatographic analysis by Ostman shows that the mononitrothiophene fraction contains as much as 16% of the 3-isomer. It appears that gas-chromatographic analysis should be very useful for the detection of small amounts of 3-isomers in other substitution reactions. However, from routine analyses of IR spectra, it appears to the present author that the amount of 3-isomers formed in acylation, formylation, and bromina-tion of thiophene are certainly less than a few per cent. 

Friedel-Crafts acylation of fluorobenzene with thiophene-l-carboxylic acid gives the ketone 7. Nitration proceeds ortho to the fluoro group to give the intermediate Nucleophilic displacement by means of... 

Disubstituted Benzo[b]thiophenes 2,3-I)ibromobenzo[6]thiophene undergoes Friedel-Crafts acylation in the 6-position,77 but gives a mixture of the 4- and 6-nitro isomer on nitration.101 Similarly, 2,3-dimethylbenzo[b]thiophene undergoes Friedel-Crafts acetylation82,136,418 and bromination81 mainly in... 

Electrophilic substitution reactions of halobenzo[6]thiophenes are considered in Sections VI,E,1 (nitration) and VI, L, 2 (Friedel-Crafts acylation). 

Benzo[ ]thienoquinones 230 are synthesized by the reaction of 2-acyl-l,4-benzoquinones with thioglycolic acid esters followed by protection of 228 with 1-trimethylsilylimidazole and oxidation of 229 with ceric ammonium nitrate (CAN) (Scheme 43) <2001H(55)2423>. Similar reaction of 4,7-dioxo-dihydrobenzothiophenes 231 affords 4,7-dioxo-dihydrobenzodithiophenes 232 <2003H(60)1689>. Synthesis of thiophenes 233 <2005H(65)2973> and 234 <2006H(68)1709> has also been reported. 

The first three reactions are all electrophilic substitution a bromination of a pyrrole, the nitration quinoline, and a Friedel-Crafts acylation of thiophene. Bromination occurs on the pyrrole at only remaining site. Nitration of quinoline occurs on the benzene rather than the quinoline r-fi (actually giving a mixture of 5- and 8-nitroquinolines, but don t worry if you didn t see t- Mi p. 1174), and the acylation would occur next to sulfur. 

Instead, these heterocycles and their derivatives most commonly undergo electrophilic substitution nitration, sulfonation, halogenation. Friedel-Crafts acylation, even the Reimer-Tiemann reaction and coupling with diazonium salts. Heats of combustion indicate resonance stabilization to the extent of 22-28 kcal/ mole somewhat less than the resonance energy of benzene (36 kcal/mde), but much greater than that of most conjugateci dienes (about Tlccal/mole). On the basis of these properties, pyrrole, furan, and thiophene must be considered aromatic. Clearly, formulas I, II, and III do not adequately represent the structures of these compounds. 

Thiophene is chlorinated by CI2 or SO2CI2. Bromination occurs by Br2 in acetic acid or with N-bromosuccinimide. Nitration is effected by concentrated nitric acid in acetic acid at 10°C. Further substitution predominantly yields 2,4-dinitrothiophene. Sulfonation with 96% H2SO4 occurs at 30°C within minutes. Benzene reacts extremely slowly under these conditions. This provides the basis for a method to remove thiophene from coal tar benzene (see p 77). Alkylation of thiophenes often gives only poor yields. However, more efficient procedures are the Vilsmeier-Haack formylation, which yields thiophene-2-carbaldehyde, and acylation with acyl chlorides in the presence of tin tetrachloride, to give 2-acylthiophenes. Like furan, thiophene is mercurated with mercury(II) chloride. 

Benzo[Z ]thiophene is somewhat less reactive in electrophilic substitutions than thiophene, and also less reactive than benzo[Z ]furan. Moreover, regioselectivity is poor, giving rise to mixtures. Frequently, the 3-position is attacked preferentially over the 2-position, e.g. in halogenation, nitration and acylation. Only the reaction with n-butyllithium is regioselective, giving 2-lithiated benzo[6]-thiophene. 

Thiophen Analogues of Phenanthrene.— Electrophilic substitutions of naphtho[2,l-6]thiophen (434) such as nitration, formylation, and acylation occur, in contrast to those in benzo[6]thiophen, in the thiophenic a-position (2-position). Bromination gives a mixture of the 2-bromo- and 2,5-dibromo-derivatives. That the 5-position is the second most reactive... 

Skraup and Conrad-Limpach reactions to appropriate benzo[6]thiophen derivatives. Substitution reactions of thieno[3,2-/]quinoline (559), which was prepared by a Skraup synthesis from 5-aminobenzo[6]thiophen, have been studied. The same method has also been used earlier for the synthesis of the 7- and 9-methyl derivatives of (559). Nitration, bromina-tion, and acylation of (559) occur in the 2-position. Some reactions of... 

Scheme 90 Use of ionic liquid EtNH3 T402 promoted by Tf20 for nitration of 2-acyl thiophenes [138]...

Alkylthio-5-alkylthiophens are chloromethylated at position 3 by chloromethyl methyl ether. 3-Methylthiothiophen has been nitrated at position 2. The influence of the reaction conditions on the isomer distribution in the acylation of 2-methoxy-, 2-methylthio-, and 2-dimethyl-amino-thiophen has been studied. Azo-coupling and aminomethylation occur at position 3 of some 4,5-disubstituted 2-acylaminothiophens. 3-Acetylamino-2-benzoylthiophen yields the 4,5-dichloro-derivative with sulphuryl chloride, while 3-acetylamino- or 3-benzoylamino-4-carbonyl-thiophen derivatives are chlorinated at position 2. ... 

Contrary to benzo[b]thiophen, benzo[b]selenophen is acylated at position 2. 2-Bromobenzo[b]selenophen, prepared from the 2-lithium derivative and bromine, is acylated at position 3, and from this derivative the 3-isomers could be synthesized. A large number of 2- and 3-aroylbenzo[b]seleno-phens were synthesized, either by Friedel-Crafts reaction of benzo-[bjselenophencarboxylic acid chlorides and benzenes or from benzol bjselenophens and benzoic acid chlorides. Also the reaction between Grignard reagents and nitriles was used for the synthesis of aroylbenzo[b]selenophens. 4,S-Diaminobenzo[b]selenophen has been synthesized via nitration of 5-aminobenzo[b]selenophen or via the reaction of the diazonium salt derived from the S-amino-derivative with p-sulphanilic acid. From the diamino-derivative, several fused benzo[b]selenophens, e.g. (525), (526), and (527), were prepared. Reaction of the phenyl-... 

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