Synthesis of 2,5-Diiodopyrazine by Deprotonative Dimetalation of Pyrazine

International audienceThe deproto-metalation reactions of pyrimidine and pyrazine were regioselectively carried out using lithium tri(2,2,6,6-tetramethylpiperidino)cadmate in tetrahydrofuran at room temperature. This result was demonstrated by subsequent trapping with iodine to afford 4-iodopyrimidine and iodopyrazine in 71 and 63% yields, respectively. The same reaction performed on pyri-dazine afforded a mixture of the 3- and 4-iodo derivatives (55 and 41% yields, respectively). From pyrazine, the access to the 2,5-diiodo derivative (40% on a 25 mmol scale) proved possible using a larger amount of base (1 equiv instead of 1/3)

Catalytic behavior of surfactant-containing-MCM-41 mesoporous materials for cycloaddition of 4-nitrophenyl azide

International audienceSi-MCM-41, Ga-MCM-41 and Al-MCM-41 mesoporous catalysts (with Si/Al = 80 and Si/Ga = 80) were prepared by direct synthesis under hydrothermal crystallization method using sodium aluminate or gallium sulfate and tetraethyl orthosilicate (TEOS) as aluminum or gallium and silica sources, respectively. The structural features of the materials were determined by various physico-chemical techniques such as X-ray diffraction (XRD), nitrogen sorption at 77 K, Fourier transform infrared spectroscopy (FTIR), scanning and transmission electronic microscopy (SEM, TEM) and thermogravimetric analysis ATG. The catalytic activity of the calcined and as-synthesized catalyst was evaluated through the cycloaddition reaction of 4-nitrophenyl azide with activated alkenes at room temperature under liquid-phase conditions. High yields of 1,2,3-triazole were obtained. For comparison purpose, mixtures of homogeneous and heterogeneous catalyst Et3N/M-MCM-41 (M = Al or Ga) are also tested. The catalyst was used in five consecutive experiments without important loss of activity, confirming its stability. Finally, a new method for preparing triazoles in short reaction times was developed

Deprotonative Cadmation of Functionalized Aromatics

International audienceThis communication describes the deproto-metalation of a large range of aromatics including heterocycles using a newly developed lithium-cadmium base. The reaction proceeds at room temperature with an excellent chemoselectivity and efficiency, and proved to be regioselective in most cases

Direct metalation of heteroaromatic esters and nitriles using a mixed lithium-cadmium base. Subsequent conversion to dipyridopyrimidinones.

International audienceAll pyridine nitriles and esters were metalated at the position next to the directing group using (TMP)(3)CdLi in tetrahydrofuran at room temperature. The 2-, 3-, and 4-cyanopyridines were treated with 0.5 equiv of base for 2 h to afford, after subsequent trapping with iodine, the corresponding 3-iodo, 2-iodo, and 3-iodo derivatives, respectively, in yields ranging from 30 to 61%. Cyanopyrazine was similarly functionalized at the 3 position in 43% yield. Ethyl 3-iodopicolinate and -isonicotinate were synthesized from the corresponding pyridine esters in 58 and 65% yield. Less stable ethyl 4-iodonicotinate also formed under the same conditions and was directly converted to ethyl 4-(pyrazol-1-yl)nicotinate in a two-step 38% yield. All three ethyl iodopyridinecarboxylates were involved in a one-pot palladium-catalyzed cross-coupling reaction/cyclization using 2-aminopyridine to afford new dipyrido[1,2-a:3',2'-d]pyrimidin-11-one, dipyrido[1,2-a:4',3'-d]pyrimidin-11-one, and dipyrido[1,2-a:3',4'-d]pyrimidin-5-one in yields ranging from 50 to 62%. A similar cross-coupling/cyclization sequence was applied to methyl 2-chloronicotinate using 2-aminopyridine, 2-amino-5-methylpyridine, and 1-aminoisoquinoline to give the corresponding tricyclic or tetracyclic compounds in 43-79% yield. Dipyrido[1,2-a:4',3'-d]pyrimidin-11-one and dipyrido[1,2-a:3',4'-d]pyrimidin-5-one showed a good bactericidal activity against Pseudomonas aeroginosa . Dipyrido[1,2-a:2',3'-d]pyrimidin-5-one and pyrido[2',3':4,5]pyrimidino[2,1-a]isoquinolin-8-one showed a fungicidal activity against Fusarium and dipyrido[1,2-a:4',3'-d]pyrimidin-11-one against Candida albicans . Ethyl 4-(pyrazol-1-yl)nicotinate and dipyrido[1,2-a:2',3'-d]pyrimidin-5-one have promising cytotoxic activities, the former toward a liver carcinoma cell line (HEPG2) and the latter toward a human breast carcinoma cell line (MCF7

Direct metallation of thienopyrimidines using a mixed lithium-cadmium base and antitumor activity of functionalized derivatives

International audienceA series of thieno[2,3-d]- and thieno[3,2-d]pyrimidines have been easily synthesized using as key step a deproto-cadmiation-trapping sequence. Some of the compounds thus synthesized were screened for anti-cancer (cytotoxic) activities, and (S)-2-(6-iodo-2-phenylthieno[2,3-d]pyrimidin- 4-ylamino)-3-phenylpropanoic acid proved to have a significant activity towards liver, human breast and cervix carcinoma cell lines

A combined experimental and theoretical study of the thermal cycloaddition of aryl azides with activated alkenes.

International audienceReactions were performed from aryl azides on the one hand, and activated alkenes coming from β-dicarbonyl compounds or malonodinitrile on the other hand, either with recourse to conventional heating or to microwave activation, to afford 1-aryl-1H-1,2,3-triazoles. The mechanism and the regioselectivity of the reactions involving β-dicarbonyl compounds have been theoretically studied using DFT methods at the B3LYP/6-31G* level: they are domino processes comprising a tautomeric equilibrium of the β-dicarbonyl compounds with their enol forms, a 1,3-dipolar cycloaddition of the enol forms with the aryl azides (high activation energy), and a dehydration process (lower activation energy). The effect of non-conventional activation methods on the degradation of 1,2,3-triazolines was next studied experimentally. Finally, some of the 1,2,3-triazoles such synthesized were evaluated for their bactericidal and cytotoxic activities

Réaction de substitution nucléophile aromatique des acides naphtoïques ortho-fluorés/méthoxylés avec les réactifs de Grignards et les organolithiens (SNArAB)

Dans ce travail, il est montré que les alkyl/vinyl/aryl lithiens et magnésiens réagissentavec les acides C-1(F/OMe) naphtoïques en l'absence de catalyseur métallique. Cette nouvelleréaction de substitution nucléophile aromatique permet potentiellement de préparer n importequel biaryle tout en s'affranchissant des étapes de protection et de déprotection de la fonctionacide (CO2H). Les alkyllithiens linéaires et ramifiés réagissent avec la même efficacité que lesalkylmagnésiens même à basse température ( 78 C). Le déplacement d'un fluor ou d'unméthoxy s'effectue avec la même facilité. L'absence d'ortho-lithiation est confirmée par lepiégeage du milieu réactionnel en fin de réaction par l'iodométhane (après addition de n-BuLi,s-BuLi et t-BuLi). Le bromure de vinylmagnésium requiert un chauffage au reflux du THF.La méthode étudiée permet de préparer extrêmement facilement des 1- et 2-phénylnaphtalènes, 1,1 -binaphtalènes et 2,2 -binaphtalènes. Dans les exemples où lesaryllithiens donnent des rendements moyens-faibles en produits de couplage, les réactifs deGrignard sont beaucoup plus efficaces. Le o-tolyllithium, le bromure de o-tolylmagnésium, lebromure de (4-méthoxyphényl)magnésium, le bromure de (2,5-diméthylphényl)magnésium etle bromure de benzo[d][1,3]dioxol-5-ylmagnésium déplacent facilement le groupefluoro/méthoxy en ortho du groupe CO2M pour donner les produits de substitutioncorrespondants alors que la réaction du bromure de (2,6-diméthoxyphényl)magnésium estmoins efficace sans doute en raison de l'encombrement stérique causé par les deux groupesortho-méthoxy. L'acide 1-(2-méthoxyphényl)-2-naphtoïque est un produit particulièrementintéressant. La déprotection du groupe méthoxy suivie d'une cyclisation est réalisée par BBr3pour donner la 6H-naphtho[2,1-c]chromén-6-one qui est isolée avec un rendement de 97 %.Cette lactone est utile pour la préparation de composés atropoisomères optiquement actifsaprès ouverture énantiosélective du cycle lactone selon la technique mise au point parBringmann.Alkyl as well as aryl substitution can be readily accomplished in generally excellentyields via a nucleophilic mode by displacement of an ortho-fluoro or methoxy group inunprotected naphthoic acids with lithium and Grignard reagents in the absence of a metalcatalyst.Alkyllithium reagents typically gave good-to-excellent yields, whether primary,secondary, or tertiary at 78 C. Displacement of a fluoro or a methoxy group occurs withequal efficacy. The absence of ortho-lithiation was confirmed by quenching the reactionproduct with MeI after addition of n-BuLi, s-BuLi and t-BuLi. Alkyl Grignard reagentsEtMgBr and n-BuMgBr proved to be very reactive at 78 C while vinyl magnesium bromiderequired refluxing in THF.The method provides excellent latitude with respect to the synthesis of 1- and 2-phenylnaphthalenes, 1,1 -binaphthalenes, and 2,2 -binaphthalenes. In those instances wherethe aryllithium reagents gave poor yields of coupling products, the corresponding Grignardreagents proved to be much more effective. o-Tolyllithium, o-tolylmagnesium bromide, (4-methoxyphenyl)magnesium bromide, (2,5-dimethylphenyl)magnesium bromide andbenzo[d][1,3]dioxol-5-ylmagnesium bromide smoothly displaced the fluoro/methoxy grouportho to the CO2M group to give the corresponding substitution products while reaction of(2,6-dimethoxyphenyl)magnesium bromide proceeded with less efficiency presumably due tosteric effects imparted by the two ortho-methoxy groups. Particularly useful is 1-(2-methoxyphenyl)-2-naphthoic acid which allows for further elaboration after the coupling isperformed. Deprotection of the methoxy group followed by cyclization was realized withBBr3 to afford 6H-naphtho[2,1-c]chromen-6-one which was isolated in 97% yield. Thislactone is the starting building block for the preparation of optically active atropisomers byenantioselective ring opening.LE MANS-BU Sciences (721812109) / SudocSudocFranceF

Antibacterial Activity of Quaternary Ammonium Salt from Diethylaminoethyl Methacrylate

A quaternary ammonium salt was synthesized from diethylaminoethyl methacrylate (DEAEMA) by quaternization with hexadecyl bromide. The resultant compound (Am-h) was characterized by FTIR and NMR spectroscopy. Its bactericidal activity was evaluated by determining minimum inhibitory concentration (MIC) values and inhibitory zone diameter against gram positive bacteria (Streptococcus sp.) and gram negative bacteria such as Acenito baumannii, Klebsiella pneumoniae and Proteus sp. respectively. The results showed that the MIC values of the synthesised compound (Am-h) were 2 μg/mL against Acenito baumannii, Klebsiella pneumoniae, Proteus sp. and Streptococcus sp

Magnetic Nanoadsorbents for Metal Remediation

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Novel polymerizable surfactants: synthesis and application in the emulsion polymerization of styrene

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