Thiophenes, acylation halogenation

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. ... 

Italian authors found the following order of decreasing reactivity in halogenation and acylation a-position in thiophene > S-position in benzo[Zi]thiophene > a-position in benzo[6]thiophene > -position in thiophene. 

The use of modern physical methods (NMR, UV, and IR spectroscopy, mass spectrometry, and gas-liquid (GLC) and thin-layer (TLC) chromatography is becoming increasingly noticeable. By 19522 few systematic studies of the preparation of derivatives of benzo [6]thiophene had been undertaken, no attempt had been made to alkylate benzo[6]thiophene by means of the Friedel-Crafts reaction, and Friedel-Crafts acylation had been little studied. Halogenation of benzo[6]thiophene had only been superficially investigated and... 

Reaction, of aromatics with lead tetracarboxylates leads to substitution of a tri(acyloxy)lead group into the aromatic. This reaction takes place more readily if the acyl group contains electron-withdrawing groups such as halogen. The reaction with thiophene has been examined [58DOK (123)295 74TL853]. 

A wide variety of substituents are tolerated. The group R can be alkyl, halogen, alkoxy, -amido, azi-domethyl, ester, aryl, aryloxy and aryloyl, and at least one ortho substituent is permissible with no loss in yield. TTie aromatic ring can also be 2-naphthyl, 9,10-dihydro-2-phenanthryl, 3-pyridyl, thiophen-2-yl or pyrrol-3-yl. The group R can be hydrogen, yl, acyl or acetic acid. Beyond Ae antiinflammatory targets, successful reaction substrates include the methyl ketones of a binaphthyl crown ether, a morphinane and a polyaromatic hydrocarbon. The preparation of ibuprofen methyl ester (38) is shown in equation (37) as a typical example. ... 

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. 

Here again, these thiophene derivatives are much less stable than their benzenoid counterparts, unless the ring is provided with other substitution. " The unsubstituted amino-thiophenes (thiophenamines) can be obtained by reduction of the nitro-thiophenes, "" but in such a way as to isolate them as salts - usually hexachlorostannates - or via Beckmann rearrangements " or Hofmann degradation, " as acyl-derivatives, which are stable. 3,4-Dinitration of 2,5-dibromothiophene, then reduction, produces 3,4-diaminothio-phene. " " Many substituted amines have been prepared by nucleophilic displacement of halogen in nitro-halo-thiophenes. In so far as it can be studied, in simple cases, and certainly in substituted amino-thiophenes the amino form is the only detectable tautomer. " ... 

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. 

Thiophene-1-oxides Thiophene-1,1 -dioxides. 2.1 Reaction with nucleophiles. 2.2 Cycloaddition reactions. 2.3 Other reactions Thiophene S,N-ylides and S,C-ylides. 3.1 Cycloaddition reactions of S,N-ylides and S,C-ylides. 3.2 Cyclopropanation reactions of S,C-ylides. 3.3 Thermal transformations of thiophene S,N- and S,C-ylides Oxothiophenes Tautomeric with Hydroxythiophenes. 4.1 Tautomerism. 4.2 Alkylation and acylation. 4.3 Condensation reactions at the methylene group. 4.4 Halogenation. 4.5 Oxidative coupling. 4.6 Cycloaddition. 4.7 2,3-Diones 4 Sulfoxides and sulfones. 4.9 Photochemistry. 4.10 Macrocyclic polyethers... 

Acylation and metallation studies on monomers, dimers, trimers, and tetramers containing linked thiophen, pyridine, pyrimidine, furan, benzofuran, benzothiophen, and indole moieties have been published/ Deuteriation, halogenation, and diazo-coupling reactions of 2-oxo- and 2-thioxo-l,2-dihy-dropyrimidinium salts have been studied and compared with results for 2,2-dialkyl-1,2-dihydropyrimidinium and 2,3-dihydro-1,4-diazepinium salts in order to demonstrate the effect of an adjacent 0x0- or thioxo-group on the properties of a 1,5-diazopentadienium system/ Vilsmeier formylation of, and tautomerism in, 2-hydroxypyrazolo[5,l-h]quinazolone and l-phenylpyrazolo[5,l-A]-quinazoline-2,9-dione have been studied/ The pyrazolo[3,4-c]pyrazole (71) has been methylated and acetylated, the major products being (72)/ ... 

---