Thiazoles, phenyl-, nitration

Dihydroimidazo[2,l-6]thiazole reacts with concentrated nitric acid at 70-80°C to form what is believed to be the 5-nitro derivative [77IJC(B)629], whereas the 6-phenyl derivative of 2,3,5,6-tetrahydroimi-dazo[2,l-fo]thiazole (as nitrate salt) gives the 4-nitrophenyl product (60%) (66JMC545). 

The nitration of 2-, 4- and 5-phenylthiazole with 1 mole of HN03 in concentrated H2S04 occurs at para-position of the phenyl ring, but not to thiazole cycle [203, 247]. It can be explained then that these compounds react in so-called conjugated acid form (protonated form), but not in base form. Analogically, 2-substituted 4-(2-furyl)thiazole is nitrated into furyl cycle 5 position however, further nitration with two moles HN03 leads to 2-substituted 5-nitro-4-(5-nitro-2-furyl)-thiazoles along with other products [234] (Scheme 27). 

Acetamidothiazole is nitrated in the same way (58, 378, 379). 2-Acetamido-4-phenylthiazole is reported to be nitrated on C-5 (380) as opposed to 2-amino-4-phenylthiazole, where nitration occurs on the phenyl ring (381). This latter result is not consistent with the other data on electrophilic reactivity in most cases 2-amino-4-arylthiazole derivatives react with electrophilic reagents at the C-5 position (see Sections rV.l.B and D). Furthermore, N-pyridy]-(2)-thiazolyl-2-amine (178) is exclusively nitrated on the thiazole ring (Scheme 113) (132, 382). 

The products of the thermolysis of 3-phenyl-5-(arylamino)-l,2,4-oxadiazoles and thiazoles have been accounted for by a radical mechanism.266 Flash vacuum pyrolysis of 1,3-dithiolane-1-oxides has led to thiocarbonyl compounds, but the transformation is not general.267 hi an ongoing study of silacyclobutane pyrolysis, CASSF(4,4), MR-CI and CASSCF(4,4)+MP2 calculations using the 3-21G and 6-31G basis sets have modelled the reaction between silenes and ethylene, suggesting a cyclic transition state from which silacyclobutane or a trcins-biradical are formed.268 An AMI study of the thermolysis of 1,3,3-trinitroazacyclobutane and its derivatives has identified gem-dinitro C—N bond homolysis as the initial reaction.269 Similar AMI analysis has determined the activation energy of die formation of NCh from methyl nitrate.270 Thermal decomposition of nitromethane in a shock tube (1050-1400 K, 0.2-40 atm) was studied spectrophotometrically, allowing determination of rate constants.271... 

A quantitative study has been carried out by Ridd and co-workers126 on the nitration of imidazole and pyrazole in 98% sulfuric acid the partial rate factors for the 4-positions of imidazolium and pyrazolium cations are 3.0 xlO-9 and 2.1 x 10-10, respectively. Thiazole and isoxazole cations are also far less reactive than benzene. As a consequence, phenyl derivatives give products substituted in the benzene ring, on sulfonation or nitration.208-210... 

Acetamido-4-phenylthiazole is nitrated at position 5 of the thiazole ring [232], in contrast to 2-amino-4-phenylthiazole, which is nitrated in the phenyl ring [233], This agrees with existing data on the reactivity of thiazoles during electrophilic substitution. N-(2-Thiazolyl)-2-aminopyridine is nitrated exclusively in the thiazole ring [222],... 

In cases where there is no free position on the azapentalene ring (e.g., 424, Scheme 19) nitration occurs in the benzene ring. For 417 and 423197 where both types of position are available, nitration occurs in the para position of the benzene ring (Scheme 19). Nitration in both positions is seen in imidazo[2,l-6]thiazoles. " The 6-phenyl derivative 418 gives a nitrate salt, which, on treatment with sulfuric acid is transformed into the p-nitrophenyl derivative. Further nitration yields a dinitro compound 437 (cf. Scheme 18, attack at a on 400), which can also be obtained directly from 418. Nitration at C-5... 

Electrophilic Substitution.—The nitration of a series of phenyl-, benzyl-, and phenethyl-thiazoles has been studied under standard conditions suitable for the mono-nitration of the most reactive example, viz. 4,5-dimethyl-2-phen-ethylthiazole. The results show that the heterocyclic ring exerts a strong... 

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