Nitrobenzo thiophenes

The synthesis and chemistry of iodonium thiophene derivatives have been studied <00AM133, 00TL5393>, for example, the preparation of 46 involved the ipso substitution of 2-stannylthiophene 45 <00CC649>. A similar ipso substitution of 2-stannylbenzo[b]thiophene 47 with tetranitromethane gave 2-nitrobenzo[ >]thiophene (48) . 

On the basis of labelling studies it has been concluded70 that an intermediate of the type (53) must be involved in the reaction of 3-bromo-2-nitrobenzo[ ]thiophene (52) with 3-(trifluoromethyl)aniline in order to account for the observed labelling patterns in the products (54) and (55). 

The C NMR data of 2-nitro- 75 and 3-nitrobenzo[3]thiophenes 76 in DMSO-r4 solutions have shown <2003T7189> the occurrence of an alternate polarization, which can involve carbons C-3, C-2, C-3a, C-7a, C-4, and C-5 of the 2-nitrobenzo[/)]thiophen-3-yl moiety. A dual-substituent-parameter treatment of the C SCS indicates a large and a low resonance contribution for aryl para- and t / -substituents, respectively, while the inductive component remains constant throughout <1995MRC883>. 

The ring-opening reactions of nitrothiophenes and nitrobenzo[/ ]thiophenes are discussed in Section 3.10.4.2.1. Another interesting ring opening is initiated by a nucleophilic attack on sulfur this is discussed in Section 3.10.2.5.4. 

In contrast, reaction of 2-nitrobenzo[. ]thiophene with -butylamine under the same conditions did not lead to any ring-opened product. Instead, the substrate underwent an oxidative nucleophilic substitution reaction. 

Reaction conditions have been systematically varied in order to maximize the yield of the ring-opened products from 3-nitrothiophene and 3-nitrobenzo[. ]thiophene <2001T8159>. The scope of the reaction has been enlarged to include 2-substituted-4-nitrothiophenes as substrates (Equation 90). Yields range from 50% to 80%. 

Likewise, both 2-nitrobenzo[3]furan 427 and 3-nitrobenzo[4]thiophene 428 give rise to the novel fused heterocycles 429 and 430, respectively (Scheme 48). 

Such [2 + 2] cycloadditions have also been observed when the alkyne is electron-rich and the benzo[6 ]thiophene electron-poor. Thus 3-nitrobenzo[6]thiophene reacts with ynamines to form the cycloadduct (285) the addition is regioselective and the product shows no tendency to isomerize to the corresponding benzothiepin (74TL2503). 

Aminothiophenes (isolated as acyl derivatives) result from reduction of nitrothiophenes (63AHC(l)l). Catalytic reduction of 2- or 3-nitrobenzo[7>]thiophene followed by immediate acylation gives acylaminobenzo[6]thiophene (70AHC(11)177). Reduction of 2-nitrobenzo[6]-thiophene with ethanolic ammonium sulfide gives thiooxindole. 

The nitrene may also attack a suitable adjacent aromatic ring. Thus 2-phenyl-3-nitrobenzo[7> jthiophene gives the condensed indole (253) on treatment with triethyl phosphite. The yield in this reaction is predictably lower than the yield of the same product obtained from the precursor (252) with the nitrene located on the phenyl ring (see Section 3.14.2.9) the reason is that in the latter case the electrophilic nitrene attacks a more electron-rich centre on the thiophene ring (72JCS(Pl)2023>. 

Mononitration of benzo[6]thiophene gives a complex mixture in which the 3-isomer predominates (73% in acetic anhydride at 25 °C) and can be separated from other isomers, which may include 4-, 5-, 6- and 7-nitro derivatives. However, benzo[6]thiophenes with electron-donating groups at the 3-position, e.g. 3-methyl-, 3-acetamido- or 3-bromo-benzo[6]thiophene, are nitrated almost exclusively in the 2-position. 2-Nitro-benzo[6] thiophene may be prepared by debromination of 3-bromo-2-nitro-benzo[6 ]thiophene, or by decarboxylation of 2-nitrobenzo[6]thiophene-3-carboxylic acid (70AHC(11)177). 

Benzo[6 jthiophenes with nitro groups at the 4-, 5-, 6- or 7-positions may be synthesized by ring closure reactions of appropriately substituted benzene derivatives. Nitration of 5-acetaminobenzo[6]thiophene gives the 4-nitro derivative, which can be hydrolyzed and deaminated to yield 4-nitrobenzo[6]thiophene (equation 44). 5-Nitrobenzo[6]thiophene is conveniently available by decarboxylation of 5-nitrobenzo[6]thiophene-2-carboxylic acid, which in turn is available by a Perkin reaction of 4-nitro-2-formylphenylthioglycoIic ester (equation 45 Section 3.15.2.3). The 7-nitro isomer may be obtained similarly. 

IR spectroscopy has been used to show that 2-aminobenzo[6]thio-phenes normally exist solely as the amino tautomer,112-114 and that 2 ii2,ii3 an(j 3-hydroxybenzo[6]thiophenes117,147 exist solely as the keto tautomers, except that compounds with an adjacent carbonyl-containing group exist mainly as the enols.109,116,147> 148 3-Hydroxy-2-nitrobenzo[6]thiophene-l,1-dioxide exists as a mixture of the keto and enol forms.149... 

The inductive and mesomeric effect of the nitro group causes considerable shifts in the spectra of nitrobenzo[6]thiophenes. The zone-A bands are shifted to lower wavelength and may not be observed at all the zone-C bands are shifted strongly toward the red and appear as an... 

Treatment of the aldehyde (86 R = H) with ethyl thioglycolate and sodium ethoxide provides an elegant single-stage synthesis of the otherwise rather inaccessible ethyl 5-nitrobenzo[6]thiophene-2-... 

The Hunsdiecker reaction has been used only twice as a potential source of bromobenzo[6]thiophenes with 3-bromo-5-nitrobenzo[6]-thiophene-2-carboxylic acid it proceeds normally to give 2,3-dibromo-5-nitrobenzo[6]thiophene,152 but with 5-nitrobenzo[6]thiophene-2-carboxylic acid the main product is 3-bromo-5-nitrobenzo[6]thio-phene-2-carboxylic acid, accompanied by smaller amounts of 2,3-dibromo-5-nitrobenzo[6]thiophene.152 497... 

Nitration of 2,3-dimethylbenzo [ijthiophene unexpectedly gives 3-methyl-2-nitromethylbenzo[ ]thiophene as the major product (33%), together with 2,3-dimethyl-6-nitrobenzo[6]thiophene (10%),... 

Nitrobenzo[6]thiophene may be prepared by reaction of the 3,4-dinitro compound with alcoholic ammonium sulfide422-538 other workers have claimed that this method yields only traces of the desired product.84 It may also be prepared by deamination of 5-amino-4-nitrobenzo[6]thiophene,162,422 or by decomposition of 4-benzo[6]-thiophene diazonium cobaltinitrite with aqueous sodium nitrite in the presence of cuprous oxide and cupric sulfate.84 7-Nitrobenzo[6]-thiophene may be obtained by the latter method (15% yield) from the corresponding amine.84... 

Nitrobenzo[6]thiophene is obtained in 10% yield by the cycliza-tion of (p-nitrophenylthio)acetaldehyde dimethyl acetal (Section IV,B) 7-nitrobenzo[6]thiophene cannot be prepared by this method.488 5-Nitrobenzo[6]thiophene84,218,338,422,538,543-545 and its 3-phenyl,333 3-methyl,298 3,6-dimethyl,330 and 7-nitro-3-phenyl334 derivatives may be obtained most conveniently by decarboxylation of the readily available (Section IV, D) 2-carboxylic acids. 5- 4 J4.54e 0. 494,548 an(j 7.494 nitro-3-acetoxybenzo[6]thiophene may be prepared almost quantitatively by cyclization reactions (Section IV, D). 

Nitrobenzo[6]thiophene undergoes bromination152 and Friedel-Crafts acetylation423 in the 3-position. 

V-Substituted 3-aminobenzo[6]thiophenes are readily obtained by heating thioindoxyl with the appropriate primary or secondary aromatic amine,539 541,553,554 or primary aliphatic amine541 (Section VI, 1,2). 3-A7,jV-I)ialkylaminobemo[ ]thiophenes are best obtained by reaction of 3-bromobenzo[6]thiophene-1,1 -dioxide with a secondary aliphatic amine, followed by reduction of the product with lithium aluminum hydride (Section VI,P,2,/).541 3-Amino-2-nitrobenzo[6]-thiophene and its A-substituted derivatives are conveniently obtained... 

Aminobenzo[6]thiophene is prepared from 7-hydroxybenzo[6]-thiophene by means of the Bucherer reaction it may be converted into 7-nitrobenzo[6]thiophene via the diazonium salt.84 5,7-Diamino-3-phenylbenzo[6]thiophene and its 2-carboxylic acid are prepared by reduction of the corresponding dinitro compound.334 Partial reduction of o,7-dinitro-3-phenylbenzo[6]thiophene-2-carboxylic acid with ethanolic ammonium sulfide affords 7-amino-5-nitro-3-phenylbenzo-[6]thiophene-2-carboxylic acid, the amino group of which may be replaced by hydrogen or iodine via the diazonium salt.334 7-Amino-4-methoxybenzo[6]thiophene is mentioned in the patent literature.560... 

Nitration of 2-acetoxymethylbenzo[6]thiophene, followed by acidic hydrolysis of the product, affords 2-hydroxymethyl-3-nitrobenzo[6]-thiophene.518... 

The usual procedure for the preparation of benzo[6]thiophene- 2,3-quinones, which involves acidic hydrolysis of an anil obtained from a thioindoxyl and an aromatic nitroso compound (usually p-nitroso-iV,iV-dimethylaniline), has been used to prepare 5-methyl-,625 5-chloro-,117 and 5- and 6-nitrobenzo[h]thiophene-2,3-quinone.626... 

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