Thiophene Beckmann rearrangement

The Beckmann rearrangement of oximes of the thiophene series has been applied (besides the preparation of 2-acetamidothiophene ) to thiophenocycloalkenones (192) which gave the cyclic amide (193) hydrolyzable to the amine (194). The Beckmann rearrangement was... 

This is the first example of a direct coupling of a diazo compound in a / position of the thiophene nucleus. The Beckmann rearrangement with the ketoxime of 2-thienylketone was found to give poor yields of the aceto-2-thiopheneamide. Furthermore, the Schmidt reaction using hydrazoic and sulphuric acids was investigated and did give rise to aceto-2-thiopheneamide but probably as an eutectic with the isomeric 2-thenoylmethylamide. 

Thieno[3,2-c][l]benzazodnes 179 and 180 have been obtained by Beckmann rearrangement of benzo[4,3]cyclohepta[l,2- 7]thiophen-4-one oxime 178 (71HCA283 Scheme 49). 

Several different reaction conditions were tested to perform the Beckmann rearrangement of the substituted thiophene 323 (equation 118). The reaction of the tosyl oxime derivative was found to be the best available method, and 324 was obtained in high yield °. ... 

Beckmann rearrangement (SOClj/McjCO) of the oximes of 2-acetyl-thieno[2,3-6] and [3,2-6]thiophene leads to the formation of 2-acetamidothienothiophenes identical with those obtained by reductive acetylation (Hj/Ni/AcjO) of the 2-nitro compound. ... 

Acetaminothiophene has been prepared by a Hofmann rearrangement of thiophene-3-carboxamide (equation 49), or by a Beckmann rearrangement of the 3-acetylthiophene oxime (Section 3.14.3.4). Dimethyl 4-amino-2,3-thiophenedicarboxylate was formed in excellent yield from the oxime of the 4-ketotetrahydrothiophene diester, which is readily available by addition of thioglycolate to dimethyl fumarate, followed by a Dieckmann cyclization (equation 50 Section 3.15.2.2.2). 

These derivatives may be obtained by reduction of the appropriate nitro derivative catalytically or with a metal-acid system, or by Beckmann or Hofmann rearrangements of suitable acyl or carboxamido derivatives. 4-Aminobenzo[6]thiophene has also been prepared by means of a Bucherer reaction with 4-hydroxybenzo[6 Jthiophene. Several 5-aminobenzo[6]thiophenes have been prepared by cyclization reactions of p-acetamino-phenylthio derivatives. 6-Acetaminobenzo[6 Jthiophenes may be obtained from the corresponding 6-acetyl derivative by Schmidt or Beckmann rearrangements. 7-Aminobenzo[6 ]thiophene can also be prepared from 7-hydroxybenzo[6 ]thiophene by a Bucherer reaction (70AHC(ll)l77). 

The oximes of 4,5,6,7-tetrahydrobenzo[6]thiophen-4-one and -7-one undergo the Beckmann rearrangement to give 146 354 451 and 147 (R = H),362 respectively. Compound 147 (R=C1) may be prepared similarly and by treating 2-chloro-4,5,6,7-tetrahydrobenzo[ ]thio-phen-7-one with ammonia in the presence of PPA.356 The oxime of 4,5,6,7 -tetrahydrobenzo [6]thiophene- 4-one affords 4-aminobenzo [6]-thiophene in a modified Leuckart reaction.241,355 The same oxime may be converted into 4-amino-4,5,6,7-tetrahydrobenzo[ ]thiophene by reduction with aluminum amalgam in methanol.452 The parent ketone also affords 4-amino-4,5,6,7-tetrahydrobenzo[6]thiophene on reaction with formamide at 165°, followed by acidic hydrolysis of the resulting 4-formylamino compound.355... 

Beckmann rearrangement, 4, 809 reactions, 4, 809 toxicity, 1, 136 Thiophene, 2-acyl-alkylation, 4, 777 synthesis, 4, 917 transacylations, 4, 760 Thiophene, 3-acyl-synthesis, 4, 918... 

A -Butylpyridinium tetrafluoroborate, containing dissolved phosphorus pentachloride, allows catalytic Beckmann rearrangement of cyclohexanone oxime giving e-caprolactam with good conversion and selectivity <2001TL403>. The same ionic liquid containing dissolved ytterbium(m) trifluoromethanesulfonate was used to perform Friedel-Crafts acylation of furan and thiophene <2005JIG398>. 

Just as in benzene chemistry, Wolff-Kischner or Clemmensen reduction of ketones is a much-used route to alkyl-thiophenes, hypochlorite oxidation of acetyl-thiophenes a good route to thiophene acids, Beckmann rearrangement of thiophene oximes is a useful route to acylamino-thiophenes and hence amino-thiophenes, and esters and acids are interconvertible without complications. 

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. " ... 

Here, the parallels with benzenoid counterparts continue, for these compounds have no special properties - their reactivities are those typical of benzenoid aldehydes, ketones, acids, and esters. For example, in contrast to the easy decarboxylation of a-acids observed for pyrrole and furan, thiophene-2-acids do not easily decarboxylate. Just as in benzene chemistry, Wolff-Kischner or Clemmensen reduction of ketones is a much-used route to alkylthiophenes, hypochlorite oxidation of acetylthiophenes a good route to thiophene acids, Beckmann rearrangement of thiophene oximes is a useful route to acylaminoth-iophenes and hence aminothiophenes, and esters and acids are interconvertible with no complications. 

The indeno[l,2-Z)]thiophene 27 was converted to 2-phenyl-4F7-indeno[l,2- )]thiophene-4-one oxime 28 by reaction with hydroxylamine in the presence of sodium acetate, which underwent the Beckmann rearrangement upon treatment with polyphosphoric acid to give 2-phenylthieno[3,2-c]quinoline-4(5/f)one 29. ... 

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