2-Bromo-3-substituted-5-nitrothiophenes

Selected substituted thiophene derivatives may also react with nucleophiles. Primary and secondary amines react with 2-bromo-3-substituted-5-nitrothiophenes to produce 11 <95T5403>. Vicarious nucleophilic substitution of hydrogen (VNS) works generally for both 2-nitro- and 3-... 

In most cases, nitrothiophenes or bromo-substituted nitrothiophenes have been used as the substrates for aromatic nucleophilic substitutiOTi. Both bromo and nitro groups can be substituted by oxygen, nitrogen or sulfur nucleophiles [156]. 

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>. 

Similarly, the kinetics of the reaction of 5-substituted 3-bromo-2-nitrothiophenes (463) with thiophenoxide have been studied (70JHC1333) and a good Hammett correlation obtained... 

Kinetic studies have been reported of the reactions of a series of 2-substituted-5-nitrothiophenes (substituent = Br, OMe, OPh, OC6H4-4-NO2) with secondary amines in room-temperature ionic liquids. The kinetic behaviour is similar to that of the corresponding reactions in methanol so that most reactions do not show base catalysis. The observation that reactivity is higher in the ionic liquids than in methanol (or benzene) is attributed to relatively poor solvation of the reagents by the ionic liquids. As in conventional solvents, 2-bromo-3-nitrothiophene shows higher reactivity than 2-bromo-5-nitrothiophene.42 Solvent effects on the kinetics of the alkaline hydrolysis of 2-phenylthio-3,5-dinitropyridine in aqueous organic solvents have been analysed.43... 

Nucleophilic and Radicaloid Substitution Reactions of Monocyclic Thio-phens. - The rate constants for the reaction of 5-substituted 2-bromo-3-nitrothiophens, in methanol, with various substituted anilines to give 5-substituted iV-(3-nitro-2-thienyl)anilines have been measured at various temperatures, It was found that the sensitivity parameters that were obtained from Hammett and Bronsted correlations were practically independent of the starting system. The kinetics of piperidino-substitution of methyl 2-methoxy-3-nitrothiophen-5-carboxylate and 5-acetyl-2-methoxy-3-nitrothio-phen, in which the methoxy-group is the leaving group, have been investigated and the mechanism has been discussed. 

Nucleophilic Substitution Reactions of Monocyclic Thiophens.—The kinetics of methoxy- and phenylthio-debromination of 3-bromo-2-nitrothiophen and 3-bromo-4-methyl-2-nitrothiophen in methanol have been studied. No primary steric effect was observed. The reactivities of 2-L-3,5-dinitro-4-isopropylthiophens (L = Br or S02Ph) with aniline, piperidine, and X-methyl-aniline have been measured in methanol and compared with those previously observed for the corresponding 2-L-3,5-dinitrothiophens. 

Nucleophilic Substitutions.— The rates of nucleophilic substitution of bromine in 3-bromo>2-nitrothiophen with o-, m-, and p-substituted thiophenoxide ions in methanol are faster than those of 2-bromo-3-nitro-thiophen with the same nucleophiles." Somewhat unexpectedly, 2,3-di-bromo-4-methyl-5-nitrothiophen reacts faster with nucleophiles such as piperidine and phenylthiolate at position 2 than does 2,3-dibromo-S-nitro-thiophen." 4-Cyano-2-nitrothiophen reacts with sodium methoxide in methanol to give the Meisenheimer adduct (107), whereas 2-cyano-4-nitro-thiophen gives the sodium salt of the carboxyimidate (108), from which methyl 4-nitrothiophen-2-carboxyiimdate can be isolated upon acidification."" If, however, 2-cyano-4-nitrothiophCT is treated with sodium methoxide in [ He]DMSO, formation of the Meisenheimer complex (109) is... 

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. 

Base catalysis of piperidino-demethoxylation of 2-methoxy-3-nitrothiophene was discussed in CHEC-I <84CHEC-I(4)74i>. The study has been extended to the reaction of 2-methoxy-5-methyl-3-nitrothiophene with pyrrolidine and piperidine <93JCR(S)440>. The push-pull nature inherent in the 2-methoxy-3-nitrothiophene system apparently makes the methoxy group a sluggish nucleofuge hence the need for catalysis. The displacement of bromine in 2-bromo-3,5-dinitrothiophene by various meta- and przra-substituted anilines also appears to be base-catalyzed <90JCS(P2)2153>. 

The bromination of 2-cyanothiophen with one equivalent of bromine in the presence of an excess of AICI3 gives 2-cyano-, 4-bromo-2-cyano-, 5-bromo-2-cyano-, and 4,5-dibromo-2-cyano-thiophen in the proportions 16 70 2 12, from which pure 4-bromo-2-cyanothiophen can easily be obtained. Nitration of 2-cyanothiophen in concentrated sulphuric acid led to mixtures of almost equal amounts of 4- and 5-nitrothiophen-2-carboxylic acid. The chloromethyl-ation of 2-acetylthiophen and 2-formylthiophen with ota -bis(chloromethyl) ether in 60—100% sulphuric acid has been studied. An increase in the acidity of the medium promoted the formation of 4-substituted products. From these products some otherwise difficultly obtainable 2,4-disubstituted thiophens were prepared. ... 

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