Synthèse et réactions SRN1 en série 5-nitrothiazole

Synthesis and Promising in Vitro Antiproliferative Activity of Sulfones of a 5-Nitrothiazole Series

“…The required starting material, 4-chloromethyl-2-methyl-5-nitro-1,3-thiazole ( 1 ), was prepared in 62% overall yield by sequential condensation between 1,3-dichloroacetone with thioacetamide [ 31 ], cyclization using ZnCl 2 in refluxing methanol, and nitration of 2-methyl-4-chloromethyl-1,3-thiazole hydrochloride [ 32 ] ( Scheme 1 ).…”

“…The synthesis of 2-methyl-5-nitro-4-phenylsulfonylmethyl-1,3-thiazole ( 2a ) by reaction of 1 with sodium phenylsulfinate in anhydrous methanol, under S RN 1 conditions [ 33 , 34 ] (inert atmosphere (Ar) and 60 W lamp irradiation), at room temperature (rt) for 24 h [ 32 ] has already been described. Based on a number of reports suggesting that chemical reactions using water as a solvent in conjunction with microwave heating [ 35 , 36 , 37 ] were more eco-friendly, we adapted this alternative method to the synthesis of 2a .…”

Regioselective Suzuki-Miyaura Reaction: Application to the Microwave-promoted Synthesis of 4,7-Diarylquinazolines

“…The first step is the condensation between 2-amino-4-chlorobenzonitrile and chloroacetyl chloride, followed by intramolecular cyclisation, to give product 2 in 67% yield [31]. Then, nitration at the 6 position gave the expected product 3 (74% yield), followed by a S RN 1 reaction with the lithium salt of 2-nitropropane [32,33] leading to the ethylenic derivative 4 (76% yield). Finally, a microwave-assisted chlorination reaction using phosphorus oxychloride in the presence of N,N-diethylaniline gave product 5, bearing two chlorine atoms in positions 4 and 7 (87% yield).…”

2,4‐Disubstituted 5‐Nitroimidazoles Potent against Clostridium difficile

“…[14,15] Previously,w es ynthesized a2 -substituted5 -nitroimidazole by unimolecular radical nucleophilic substitution (S RN 1), RP 57967, which was shown to be fivefold more active than metronidazole against Clostridium perfringens with higherm utagenicity ( Figure 1). [16][17][18][19] Extendingo ur research program, [20,21] we obtained a4-substituted5-nitroimidazole with achlorophenylmethylsulfone moiety by vicarious nucleophilic substitution of hydrogen (VNS). [22] This compound was characterized by lower mutagenicity and highera ntiparasitica ctivity than metronidazole ( Figure 1).…”