Thiophenes 3-bromo

Benzo[6]thiophene, 2-(aryloxymethyl)-3-chloromethyl-synthesis, 4, 872 Benzo[6]thiophene, 2-arylthio-synthesis, 4, 931 Benzo[6]thiophene, 2-bromo-reaction with potassamide, 4, 829-830 synthesis, 4, 934 Benzo[6]thiophene, 3-bromo-Grignard reagents, 4, 831 reactions, 4, 830 synthesis, 4, 934 Benzo[6]thiophene, 4-bromo-synthesis, 4, 878, 934 Benzo[6]thiophene, 5-bromo-electrophilic substitution, 4, 797 Benzo[6]thiophene, 6-bromo-synthesis, 4, 878, 934 Benzo[6]thiophene, 5-t-buty 1-3-methyl-synthesis, 4, 880... 

Benzo(6]thiophene halogenation, 57, 294 iodination, 59, 254 resonance energy, 56, 352 Ru, Ir complexes, 58, 150 Benzo[6]thiophene, 3-benzoyl-, reaction with hydrazine, 56, 128 Benzo[l)]thiophene, 3-bromo-, chlorination, 57, 293 Benzo[6]thiophene, 4-fluoro-, 60, 17 Benzo[/>)thiophene, 4,5,6,7-tetrafluoro-2,3-dihydro-2-methyl-, 60, 28 Benzo(e]thiophenes, resonance energy,... 

Methylthiophene is metallated in the 5-position whereas 3-methoxy-, 3-methylthio-, 3-carboxy- and 3-bromo-thiophenes are metallated in the 2-position (80TL5051). Lithiation of tricarbonyl(i7 -N-protected indole)chromium complexes occurs initially at C-2. If this position is trimethylsilylated, subsequent lithiation is at C-7 with minor amounts at C-4 (81CC1260). Tricarbonyl(Tj -l-triisopropylsilylindole)chromium(0) is selectively lithiated at C-4 by n-butyllithium-TMEDA. This offers an attractive intermediate for the preparation of 4-substituted indoles by reaction with electrophiles and deprotection by irradiation (82CC467). 

Benzo[b]thiophene-2-carboxylic acid, 3-bromo-synthesis, 4, 890... 

Thiophene, 2-bromo-3-methyl-synthesis, 4, 933-934 Thiophene, 2-bromo-5-methyl-reactions, 4, 829 Thiophene, 4-bromo-3-methyl-synthesis, 4, 934... 

Thiophene-2-carbaldehyde, 3-bromo-synthesis, 4, 81 Thiophenecarbaldehydes benzothiophene synthesis from, 4, 906 reactions, 4, 807 synthesis, 4, 148 Wittig reactions, 4, 807 Thiophene-2-carb aldehydes bromination, 4, 753 conformation, 4, 33 halogenation, 4, 753 reactions, 4, 72-73 reactivity, 4, 72-73 reduction, 4, 776 Thiophene-3-carb aldehydes conformation, 4, 33 reactivity, 4, 72... 

Thiophene-4-carboxylic acid, 3-bromo-debromination, 4, 78 Thiophenecarboxylic acids acidity, 4, 71... 

The reduction of the C— Br and C—1 group moments from 1.10 and 0.90 in bromo- and iodo-benzene to about 0.80 and 0.50 in 2-bromo- and 2-iodo-thiophene has been ascribed to the larger weight of resonance forms such as (8) and (9) in the thiophene series. The chlorine, nuclear, quadrupole, resonance frequencies of chloro-substituted thiophenes are much higher than those of the corresponding benzene derivatives. This has been ascribed to a relayed inductive effect originating in the polarity of the C—S o-bond in thiophenes. The refractive indices, densities, and surface tension of thiophene, alkyl- and halo-thiophenes, and of some other derivatives have been... 

Substituted thiophenes, such as 2-iodo-, 2-bromo-, 2 chloromethyl-, and 2-acetyl-thiophene have been obtained by reacting crude, coal-tar benzene with the appropriate reagents. ... 

Dichlorothiophene can also be used for the synthesis of 3-substituted thiophenes, since it can be smoothly acylated and chloro-methylated in the 3-position, and the halogens can then be readily removed at the appropriate stage. 3-Thenylsuccinic acid (28) has thus been obtained by treating 2,6-dichloro-3-thenylsuccinic acid with sodium amalgam. 2-Bromo-3-thenylbromide can be utilized in a similar way. ... 

Finally, certain 3-substituted compounds can be prepared by utilizing the - meta) directing powet (cf. Section IV,B) of some groups in the 2-position which afterward can be removed. 3-Nitrothiophene is prepared by nitration of 2-thiophenesulfonyl chloride and by removal of the sulfonic acid group of the 4-nitro-2-sulfonyl chloride formed with superheated steam. Another approach to 3-nitrothio-phene is to nitrate 2-cyanothiophene, separate the 4-nitro-2-cyano-thiophene from the 5-isomer, hydrolyze, and decarboxylate. A final method of preparation of 3-nitrothiophene is by simultaneous de-bromination and decarboxylation of 5-bromo-4-nitro-2-thiophene-carboxylic acid obtained through the nitration of methyl 5-bromo-2-thiophenecarboxylate. 

With weakly directing — I + M-substituents such as the halogens, the a-directing power of the ring sulfur dominates and substitution appears to occur exclusively in the 5-position. 2-Chloro-, 2-bromo-, and 2-iodo-thiophene are sulfonated both with chlorosulfonic aeid and in the 5-position. In the chlorination of chloro-... 

This activation of the ortho position is most strikingly illustrated in the reactivity of 2,5-dimethylthiophene, which competitive experiments have shown to undergo the SnCb-catalyzed Friedel-Crafts reaction more rapidly than thiophene and even 2-methylthiophene. The influence of the reagent on the isomer distribution is evident from the fact that 2-methoxythiophene is formylated and bromi-nated (with A -bromosuccinimide) only in the 5-position. Similarly, although 3-bromo-2-methylthiophene has been detected in the bromi-nation of 2-methylthiophene with bromine, only the 5-isomer (besides some side-chain bromination) is obtained in the bromination of alkylthiophenes with A -bromosuccinimide. ° However, the mechanism of the latter type of bromination is not established. No lines attributable to 2-methyl-3-thiocyanothiophene or 2-methyl-3-chIoro-thiophene could be detected in the NMR spectra of the substitution products (5-isomers) obtained upon thiocyanation with thiocyanogen or chlorination with sulfuryl chloride. 2-Methyl- and 2-ethyl-thiophene give, somewhat unexpectedly, upon alkylation with t-butyl chloride in the presence of Feds, only 5-t-butyl monosubstituted and... 

From resonance structure (12) it is obvious that a —I—M-substit-uent strongly deactivates the 2-position toward electrophilic substitution, and one would thus expect that monosubstitution occurs exclusively in the 5-position. This has also been found to be the case in the chlorination, bromination, and nitration of 3-thiophenecarboxylic acid. Upon chlorination and bromination a second halogen could be introduced in the 2-position, although further nitration of 5-nitro-3-thiopheneearboxylic acid could not be achieved. Similarly, 3-thiophene aldehyde has been nitrated to 5-nitro-3-thiophene aldehyde, and it is further claimed that 5-bromo-3-thiopheneboronic acid is obtained upon bromination of 3-thiopheneboronic acid. ... 

The position of substitution in disubstituted thiophenes can, in most cases, easily be deduced from the directing effect of each substituent. Thus with a - -M-substituent in the 2-position and a —M-substituent in the 5-position, both substituents direct the entering group to the 3-position as is exemplified by the nitration of methyl 2-bromo-5-thiophenecarboxylate to methyl 2-bromo-3-nitro-5-thio-phenecarboxylate (109) or in the chlororaethylation of methyl 2-methyl-5-thiophenecarboxylate to methyl 2-methyl-3-chloromethyl-5-thiophenecarboxylate (110). °... 

In the reactions of 2,5-disubstituted thiophenes elimination of an a-substituent occurs to a much greater extent than in the benzene series. The Friedel-Crafts acetylation of 5-bromo-2-ethylthiophene in the presence of SnCE gives 2-ethyl-5-acetyIthiophene. Elimination of an a-bromine occurs also in the chloromethylation of 2,5-di-bromothiophene, leading to a mixture of 2-bromo-5-chloromethyIthio-phene and 2,5-dibromo-3-chloromethyIthiophene. Bromine atoms at both the and -position are exchanged for chlorine in the... 

Halothiophenes, which are not activated through the presence of —I—M-substituents, undergo substitution smoothly under more forcing conditions with copper salts in pyridine or quinoline. Hence 3-cyanothiophene and 5-methyl-2-cyanothiophene have been obtained from the corresponding bromo compounds. 2-Bromothiophene reacts readily with aliphatic cuprous mercaptides in quinoline at 200°C to give thioethers in high yields. The use of the copper-catalyzed Williamson synthesis of alkoxythiophenes from iodo- or bromo-thiophenes and alcoholate has been mentioned before. The reaction of 2-bromothiophene with acetanilide in nitrobenzene in... 

Many stilbenelike thiophene compounds have been prepared for a study of estrogenic activity, especially by Buu-Hoi et al. Thiophene derivatives of nonhydroxylated stilbene types showed no significant activitywhereas weak estrogenic activity was found in 5-acetyl-, 5-propionyl-, and 5-benzoyl-2-(-stilbenyl)thiophene. 1-Bromo-l,2-diphenyl-2-(5-bromo-2-thienyl)ethylene (258) was found to inhibit body growth and to produce extensive testicular atropy in male rats. A thiophene analog of estrogenic isoflavones (259)... 

The nature of the brominating medium has an influence on reaction products. Although there is no need for strongly acidic reagents, a buffer is frequently added to adsorb HBr [81H(15)1285]. When 2,3-dibromobenzo[f>]thiophene was brominated in sulfuric acid with silver sulfate present, a small amount of the 4-bromo (but none of the expected 5-bromo) derivative was observed [70JCS(C)1949]. 

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