4-Methyl-2-nitrothiophene

Electrophilic Substitution Reactions of Monocyclic Thiophens.— The reaction of thiophen with iV-(methylsulphonyl)hexafluoroacetoneimine gave (34) in 57% yield. Nitration of 3-(diacetoxymethyl)thiophen with acetyl nitrate or cupric nitrate in acetic anhydride gave the 5- and 2-isomers in the ratio 2.3 3.0. The product composition from the nitration of 3-methylthiophen was determined to be 3-methyl-2-nitrothiophen, 78% 3-methyl-4-nitrothiophen, 2.1% and 4-methyl-2-nitrothiophen, 20%. ... 

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. 

However, 4-methyl-2-nitrothiophene under the same reaction conditions, and with various amines, gave only 3-methyl-2-amino-5-nitrothiophenes - products of oxidative nucleophilic substitution of hydrogen (ONSH) at C-5, in good yields with no trace of ring opening (Scheme 128) [183]. 

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. 

Using these assumptions and conventions, Imoto and co-workers have correlated a number of series of reactions of thiophenes and furans. The reactions studied are the acid-base equilibria pK values) and the acid catalyzed methylations (thiophenes only) of thiophene-and furan-carboxylic acids and the alkaline hydrolyses of their ethyl esters the side-chain bromination of the a-acetylthiophenes, and the a-mercuration of thiophenes and the polarographic half-wave potentials of the methyl esters of thiophene- and furan-carboxylic acids and of nitrothiophenes. The pK values were determined and the ester hydrolyses studied for all three substitution orientations in the thiophene series. For the 4-R-2-Y and 5-R-2-Y series, the p-values do not appear significantly different and the data could probably be combined into a single series unfortunately, however, no limits of accuracy are reported for the p-values, and some of the raw data are not readily available so recalculation is not easily possible. For the 5-R-3-Y series the p-values deviate considerably from the other values however, whereas they are higher for the pK values, they are lower for the ester hydrolyses, and it is possible that the differences are neither systematic nor significant. 

The testing of 2-nitrobenzyltriphenylphosphonium bromide and methyl 4-formylbenzoate and four other aldehydes, 3-benzyloxybenzaldehyde, 2-naphthaldehyde, 5-nitrothiophene-2-carboxaldehyde and 4-[3-dimethylamino)propoxy]benzaldehyde, has been reported [13]. 

Cyano-4-nitrothiophene (121 X = H, Y = N02, Z = CN) shows an anomalous behavior in MeOH solution, as illustrated in Scheme 9. Whereas in DMSO-tA this compound shows the behavior common to the series 69 and is converted to adduct 123, in methanol it undergoes attack at the 2-cyano group. 72 The resulting anion 124 exhibits spectral features (Amax = 245, 270(sh) nm 8 8.67, d 8 8.25, d J = 1.5 Hz) similar to those of the starting substrate (A = 237, 262(sh) nm 8 8.87, d 8 8.30, d J = 2 Hz), and mild acidification and evaporation of the solvent yields methyl 4-nitro-2-thio-phenecarboxyimidate (125). It has been shown, by using the stopped-flow... 

With secondary amines such as piperidine or dimethylamine the formal products (372) of cine substitution are obtained with primary amines (e.g. t-butyl amine), in addition to the displacement product (376), a rearranged product (377) is obtained in which the nitrogen-bearing methyl becomes exocyclic (80CC23). Earlier studies on the reaction of 2-nitrothiophene with secondary amines showed that ring-opened products (378) are obtained (74JCS(Pl)2357). 

The thiophene ring is opened and sulfur extruded as hydrogen sulfide when 3,4-dinitrothiophene is reacted with piperidine. The product contains two nitroenamine units coupled to each other (Scheme 140). Other secondary amines react similarly (69CC549). Secondary aliphatic amines also react with 2-nitrothiophene to form the nitrodienamines (426) in 50-80% yield. It is believed that the reaction involves addition of the amine at position 5, followed by proton transfer and ring opening to give the thiol which, in the presence of air, oxidatively dimerizes to (426) (Scheme 141). In one case the thiol has been trapped as the silver salt and methylated (74JCS(P1)2357). 

Treatment of A-[l-(dimethylamino)ethylidene]benzenecarboselenoamide (103) with ethyl bromopyruvate in the presence of triethylamine affords 5-[(ethoxy carbonyl)acetyl]-4-methyl-2-phenyl-l,3-selenazole (104) (Scheme 31) [179], In a similar reaction of morpholino(selenocarbonyl)-amidines with 2-(chloromethyl)-5-nitrothiophene other substituted 1,3-selenazoles were obtained [180],... 

Methoxide addition in basic methanolic solutions has been reported for various mononitro- and dinitrothiophenes and -selenophenes. The presence of C-2 adducts (177) has been established for each of the thiophenes and selenophenes in Table VIII.330-336 2-Nitro-3-methoxythiophene adds methoxide at C-5 in dimethyl sulfoxide to give 178.330 No adduct could be observed for 2-methyl-5-nitrothiophene under the same conditions.330... 

Similarly, treatment of 2-nitroethylene-l,l-dithiolate with a-halocarbonyl compounds results in derivatives of 3-nitrothiophene-2-thiol.29 The products are isolated either by oxidation to the disulfides (33) or by S-methylation (34) (Scheme 7). 

The scope of the above Ag -mediated ring opening of 3-nitrothiophene has been extended to 3-nitrobenzo[3]thio-phene <1997T8531>. Nitroenamines 191 have been obtained after methylation (Equation 89). 

A long-standing analysis of the ESR spectrum of 2-nitrothiophene anion-radical 115 has been confirmed by more recent investigations the earlier paper also presented a treatment of the 3-isomer 116 and various methylated derivatives while one of the latter investigated the influence of... 

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. 

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