Nitro-debromination

Nitration in 80% sulfuric acid of 4-bromopyrazoles gives rise to considerable nitro-debromination (formation of 4-nitropyrazoles) (79AJC1727). The reaction takes place on the protonated pyrazolium ion (Section 4.04.2.1.4(ii)). 

Similar results were then found for piperidino-debromination of various nitro-activated five-membered ring heterocycles103. The existence of such linear Hammett plots for ortho-substituted substrates was interpreted as a peculiar feature of five-membered ring heterocycles, where steric effects of substituents ortho to the site of the nucleophilic attack are minimized13. 

Viologen salts act as one-electron phase-transfer agents and, in conjunction with sodium dithionite which regenerates the bipyridinium radical cation, they have been used for the debromination of 1,2-dibromoalkanes to yield alkenes in variable yields [13-15]. Nitroarenes are reduced to anilines in high yield (>90%) under similar conditions [16], whereas conjugated nitroalkenes are converted into the oximes of the saturated ketones [17] saturated aliphatic nitro compounds are not reduced by this process. 

Related homoberbine derivative 427, when debrominated, provides a second access to target 160 (69JC874). Finally, inhibitor precursor 84a on nitration gives 9- and 11-nitro derivatives 428 (27 and 64%, respectively) after esterification, deprotection, and amidation (analogously to the formation of 82a from 81a), reduction (H2, Pd-C) affords the respective amino or sulfonylamino compounds (92EPP492369, 94WO28901, respectively). 

The activated halogenothiophene is more reactive than a similarly activated halogeno-benzene. A quantitative study of the rate of piperidino-debromination of six isomeric bromonitrothiophenes reveals that these substrates react considerably faster than the corresponding bromonitrobenzenes. As in electrophilic substitution, the 2,3-, 2,4- and 2,5-relationships have been equated to ortho, meta and para substitution in benzene derivatives. Although there is some validity in this, a few inexplicable results have been encountered in the above study thus 2-bromo-4-nitrothiophene reacts much faster than either 2-bromo-3-nitro- or 2-bromo-5-nitro-thiophene (64AHC(3)285>. 

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). 

Orthanilic acid was first made by the reduction of nitro-benzenesulfonic acid by ammonium sulfide.2 This reduction has also been carried out electrolyticallv, and by the use of iron or zinc.3 The acid has also been made by the rearrangement of phenylsulfamic acid,4 by the action of sodium hypobromite upon potassium o-carbaminebenzenesulfonate,5 by the reduction of the mixed nitrobenzenesulfonic acids followed by separation of the isomers,6 by the action of methyl alcohol upon o-nitro-phenylsulfurchloride,7 by the action of acid upon diacetyl diphenylsulfamide,8 by the debromination of />-bromoaniline-e-sulfonic acid,9 by the reduction of 1,2,6-aminothiophenolsulfonic acid,10 and by the hydrolysis and reduction of e-nitrobenzene-sulfonyl chloride, which was obtained from di-o-nitrophenyl-disulfide.11... 

Selenophene compounds are also more reactive in nucleophilic substitutions. Thus, 3-nitro- and 5-nitro-2-bromoselenophenes90 react with piperidine faster than do the corresponding thiophenes.91 The effect of electron-accepting substituents on the nucleophilic substitution of bromine located at the 2-position of 3,5-disubstituted selenophenes has been studied, as also has the applicability of the Hammett equation to this piperidino-debromination.92... 

In A,A-dimethylformamide, antz-debromination of erjt/ ro-l,2-dibromo-l-(4-nitrophenyl)-2-phenylethane with (zz-C4H9)4N CN gives 99 emol/mol 4-nitro-trazr>s-stilbene. As the solvent composition approaches pure ethanol, the proportion of a-bromo-4-nitro-czs -stilbene, the product of azztz-dehydrobromination, increases to 90 emol/mol. The E2C reaetion involves a looser activated eomplex, better solvated by protie solvents than its tighter E2Br-like eounterpart [396]. 

Two DHPs were obtained from tetramethoxystilbene [279]. Substitution by a nitro group in the meta or para position reduces distinctly [82], Saltiel et al. have questioned whether the values may be erroneous [105], On the basis of quenching measurements with azulene they proposed additional routes for bromostilbenes from c via excited states of DHP which may relax back to 3c or c. A consequence of a higher value of for the mechanism of cis -> tram isomerization is that the ratio of c decaying to the trans isomer may have to be reexamined. For trans-ct-bromostilbene and the / -phenyl substituted derivatives several photoreactions (e.g., debromination) compete with photocyclization [475]. Interestingly, no evidence for photocyclization could be found for several fluorinated stilbenes [481]. Rotamers can be distinguished in the cyclization of c/s-2,2 -DNE [482],... 

Spinelli and co-workers have shown that linear free-energy or/Ao-correlations can be successfully established for the nucleophilic displacement reactions on activated halogenothiophenes. This has been validated on the benzenethiolate debromination of 2-bromo-3-A -5-nitrothiophenes (557) <91JCR(S)270>, the chlorine-isotopic exchange between ClLi, and some 2-chloro-3-3T-5-nitro-thiophenes (558) <88JCR(S)198>, and the piperidino-debromination of some 2-bromo-3-A -4-methyl-5-nitrothiophenes (559) <85JCS(P2)519>. 

Taxol analogs labeled at the 2-position have been prepared by Kingston and by Georg. The tritiated 2-(m-azidobenzoyl) analog 11.2.10 was prepared by reductive debromination of the corresponding 3-nitro-4-bromobenzoyl derivative with sodium [ H]-borohydride (393), and the corresponding non-radioactive analogs 11.2.11 and 11.2.12 were prepared by standard methods (388). 

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