Michel P. Crozet

Synthesis of novel functionalized 5-nitroisoquinolines and evaluation of in vitro antimalarial activity

Summary Novel aldimine and hydrazone isoquinoline derivatives were obtained after subjecting 1-formyl-5-nitroisoquinoline to classical reactions. Some of these compounds were found to have activity against a chloroquine-resistant Plasmodium falciparum strain (ACC Niger).

Genotoxicity in oxazolidine derivatives: influence of the nitro group

Abstract Tris-(hydroxymethyl)-aminomethane reacts with various aromatic or heterocyclic aldehydes, leading to new mono- or bicyclic oxazolidine derivatives. The importance of molecular surroundings of the nitro group has been evaluated by the genotoxic study of synthetised compounds using metronidazole and dimetridazole as reference compounds.

SRN1 reactions of a tetrasubstituted-1,4-benzoquinone

Abstract The C-alkylation reaction of 2-chloromethyl-3,5,6-trimethyl-1,4-benzoquinone by 2-nitropropane anion is shown to proceed by the S RN 1 mechanism. This mechanism is confirmed by the inhibitory effects of dioxygen, p-dinitrobenzene, cupric chloride and di-tert-butylnitroxide. The dioxygen-induced formation of nitro and nitrite derivatives is found for the first time.

SRN1 reactions in imidazo [1, 2-a] pyridine series

2-Chloromethyl-3-nitroimidazo[1,2-a]pyridine is shown for the first time to react with 2-nitropropane salts by an SRN1 mechanism to give excellent yield of isopropylidene derivative formed from the C-alkylation product by loss of nitrous acid.

Reactions SRN1 en serie heterocyclique: II. Reactivite du methyl-1 chloromethyl-2 nitro-5 imidazole.☆

Abstract 1-Methyl-2-chloromethyl-5-nitroimidazole reacts with tertiary nitronate anions in excess to afford in high yields the previously unknown 1-methyl-5-nitro-imidazoles bearing a trisubstituted ethylenic double bond in the 2 position. These compounds are ascribed to a C-alkylation reaction according to the SRN1 mechanism followed by base-promoted nitrous acid elimination.

Réactions SRN1 en série hétérocyclique. IV: Réactivité des sels du diméthyl-2,2 nitro-5 dioxanne-1,3

Abstract 2-Alkyl 2-nitro 1,3-propanediol, 2-alkylidene 1,3-propanediol and 2-dialkylidene 1,3-propanediol are prepared via S RN 1 reactions with salts of 2,2-dimethyl 5-nitro 1,3-dioxane and acid-catalyzed cleavage of the resulting acetals.

SYNTHESE ET REACTIONS SRN1 EN SERIE 5-NITROTHIAZOLE

A new heterocyclic reductive alkylating agent, the 2-methyl-4-chloromethyl-5-nitrothiazole, has been synthesized and could react with the 2-nitropropane anion as nucleophile, to give the 2-methyl-4-(2-methylpropenyl)-5-nitrothiazole as the major product. The reaction was shown to proceed by the SRN1 mechanism which was confirmed by the classical criteria for SRN1 reaction: the leaving group effect, the electronwithdrawing group effect and classical inhibition experiments by dioxygen, p-dinitrobenzene, cupric chloride or di-tert-butylnitroxide. This reaction has been extended to nitrocyclopentane and nitrocyclohexane anions with lower yields.

Synthèse et réactions srn1 en série 3-nitroimidazo[1,2-a]pyrimidine

Abstract A new heterocyclic reductive alkylating agent, 2-chloromethyl-3-nitroimidazo[1,2-a] pyrimidine, is synthesized for the first time and shown to react under phase-tranfer catalysis conditions with 2-nitropropane anion to give good yield of the C-alkylated derivative. Elimination of nitrous acid allows to obtain a new class of imidazo[1,2-a]pyrimidine derivatives bearing a trisubstituted ethylenic bond in the 2 position. The SRN1 mechanism of C-alkylation is confirmed by classical inhibition experiments by dioxygen, p-dinitrobenzene or TEMPO.

Electron transfer reactivity in 5-nitrouracil series☆

Abstract The sodium salt of 1,3,6-trimethyl-5-nitrouracil is shown to react with various reductive alkylating agents such as p-nitrobenzyl chloride and dinitropropane by an S RN 1 mechanism to give new potentially bioactive 5-nitrouracil derivatives. 1,3-Dimethyl-5-nitro-6-chloromethyluracil also reacts by an S RN 1 mechanism with 2-nitropropane anion to afford a new uracil derivative bearing a trisubstituted ethylenic double bond at the 6-position.

Synthèse par réaction sRN1 de nouveaux dérivés en série imidazo[1,2-α]pyridine à potentialités pharmacologiques

Abstract The study of S RN 1 reaction between 2-chloromethyl-3-nitroimidazo[1,2-a] pyridine and 2-nitropropane salts has been extended to various aliphatic, cyclic and heterocyclic nitronate anions. From C-alkylation products, base-promoted nitrous acid elimination afforded new potential pharmacological derivatives with a trisubstituted double bond at the 2 position.