New azo-decorated N-pyrrolidinylthiazoles: synthesis, properties and an unexpected remote substituent effect transmission

Abstract

New 5-azo substituted thiazole derivatives have been obtained, under mild conditions and in good yields, by the reaction between 2-N-pyrrolidinylthiazole and a series of aryldiazonium salts bearing, mainly in the para position, groups with different electronic effects. The NMR spectra of the products show broad signals of the methylene groups in the alpha position to the pyrrolidinyl nitrogen, suggesting a hindered rotation around the C2-N bond, of which a double bond character was also evidenced by X-ray diffraction analyses. The free energies of activation for the rotational processes have been obtained from (1)H NMR experiments and computer simulations at different temperatures and provided good correlation with the σ constants of the substituents on the 'remote' benzene ring. This represents an unexpected and peculiar result since the restricted rotation around the C2-N bond was shown to be influenced by a substituent situated very far away. 2,4-Di-N-pyrrolidinylthiazole showed a much greater reactivity than 2-N-pyrrolidinylthiazole with aryldiazonium salts.

Nucleophilic Cyclization/Electrophilic Substitution of (2,2-Dialkoxyethyl)ureas: Highly Regioselective Access to Novel 4-(Het)arylimidazolidinones and Benzo[d][1,3]diazepinones

“…The six-membered cyclic urea moiety is also found in a number of drugs, such as well-known barbiturates, the anti-HIV drug lopinavir, 12 the antibiotic sparsomycin, 13 and the actively studied anticancer agent troxacitabine. 14 Other examples of cyclic ureas of biological importance include 1,3-diazepinone derivatives, which possess anti-HIV [15][16][17][18][19][20][21][22] and anticancer [23][24][25][26] activity and were proposed for the treatment of Alzheimer's and Parkinson's disease. 27 The conventional approach to cyclic ureas involves carbonylation of variously substituted diamines with phosgene.…”

Intriguing enigma of nitrobenzofuroxan's ‘Sphinx’: Boulton–Katritzky rearrangement or unusual evidence of the N-1/N-3-oxide rearrangement?

“…Thus, only the products 5a-c derived from the nucleophilic attack at C-5 were expected to be formed (Scheme 5), as previously found for aryldiazonium salts. 39 As soon as the reaction between 3a-c and 7-chloro-4,6dinitrobenzofuroxan (4, or ClDNBF), run at room temperature in acetonitrile with 2 : 1 molar ratio, started, the color of the mixture turned from pale yellow to deep blue.…”

“…38 On the other hand, 2,4-dipyrrolidinyl thiazole is such an activated nucleophile that gives a very complicated mixture of products when reacted with electrophiles such as aryldiazonium salts. 39 On the contrary, when 2-pyrrolidinylthiazole reacted with aryldiazonium salts, the corresponding azo derivatives bound in position 5 (ref. 39) of the thiazole ring were formed in good yields.…”

“…39 On the contrary, when 2-pyrrolidinylthiazole reacted with aryldiazonium salts, the corresponding azo derivatives bound in position 5 (ref. 39) of the thiazole ring were formed in good yields.…”

Synthesis, Reactivity and Applications of Aryl Azothiazoles Derivative.

“…Res. 5 (7), 2426-2496 2438 Treatment of 2,4-dipyrrolidinylthiazole 109 with arenediazonium salts 110a-c afforded 5-(4-Nitrophenyl)diazenyl-2,4-dipyrrolidin-1-yl-1,3-thiazole 111a and 5-(4-Bromophenyl)diazenyl-2,4-dipyrrolidin-1yl-1,3-thiazole 111b and 5-(4-methoxyphenyl)diazenyl-2,4-dipyrrolidin-1-yl-1,3-thiazole 111c (Boga, Cino et al 2016) Coupling of 4-aryl-1,3-thiazol-2-amine 113 with diazonium salt solution 112 afford 4-(substituted)-5-(phenyldiazenyl)-1,3-thiazol-2-amine 114, then the product reacted with methacryloyl chloride 115 or condensed with methacrylic acid 116 in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI) to afford 2methyl-N-[4-aryl-5-(aryldiazenyl)-1,3-thiazol-2-yl]acrylamides 117. Copolymers (119) produced from the reaction of 2-methyl-N-…”