β-Dicéto énamines hététrocycliques: 1. Indanediones-1,3 substituées en 2 par un hétérocycle azoté

The condensation of methylated N-heterocycles and espically monomethyl- and polymethylpyridinets on phthalic enhydrides leads to 2-ary1-1,3-indanediones. The 3alklidenylphthalides formed in an intermediary state have been isloated. The influence of solvents and temperature on the velocity and yeild of formation of 2-(2- and 4-pyridyl)-1,3-indandiobnes has been studies. The ir and nmr spectra confirm taht these compunds exist under a β-diketoenamine form resonating witj a betaine form.     

Réaction d'énamines dérivées de la cyclohexanone avec le tétracyanoéthylène

Reaction with Tetracyanoethylene of Enamines derived from Cyclohexanone At room temperature enamines of cyclohexanone react with tetracyanoethylene (TCNE) to give substituted tetrahydroindenes 5 . The structures are assigned on the basis of ¹³C-NMR. data and confirmed by hydrolysis. Spectroscopic studies (IR., UV., ESR.) at different temperatures indicate that the reaction can follow two routes: classical zwitterion formation, or a concurrent electron transfer between the enamines and TCNE leading to the derivates 5 . These are the first reported examples of the γ-carbon reactivity of an enamine.     

Etude expérimentale et théorique de la substitution de N-méthyl-halogéno-triazoles-1,2,4 par les réactifs nucléophiles

Kinetic studies of the substitution of isomeric N-methyl-halogeno-1,2,4-triazoles with piperidine or the methoxide ion have been carried out. The experimental results show that the 1-mcthyl-5-halogcno isomer is more reactive than the 4-methvl-3-halogeno isomer. Various theoretical treatments of the reaction have been applied. The calculations show that the “frontier charge” and “delocalised bond” models give (he best results.     

Pipérazinediones-2,5. 2. Les acides dioxothiazolidino pipérazine carboxyliques et leurs dérivés désulfurés

We have recently described a new synthetic route which has been used in our laboratory for the preparation of several novel heterocyclic systems comprising, the I,l-dimethylthiazolidino[3,4-o)piperazine-5,8- dione-3-carboxylic acid and the 2,2-dimethylthiazolidino[3,2-a]piper- azine-5,8-dione-3-carboxylic acid (8). The former was obtained with quan- titative yield and the latter with 71% yield. As a development of our studies on novel 2,5-piperazinedione systems, we describe in this report, the synthesis of the (2,5-dioxopiperazinyl)2-isobutyric acid (9), then-butyl(2-isopropyl)3,6-dioxopiperazinyl-l) acetate (1 l), and another synthetic route, illustrated in Scheme I, by which the compound 8 was obtained with quantitative yield. Spectrometric data were obtained and their interpretation confirms the proposed structure of the new compounds.     

Nouveaux exemples de radicaux libres stables de dérivés hétérocycliques de sucres. Communication préliminaire

Some more examples of stable free radicals of carbohydrate heterocyclic derivatives 2-Glycosyl-4,4,5,5-tetramethylimidazoline- 3-oxide-1-oxyls and 2-glycosyl-4,4,5,5-tetramethylimidazoline 1-oxyls have been prepared in nine carbohydrate series, which proves the generality of the method. The hyperfine coupling constant between the free electron and the α-proton of the glycosyl group is never very large (0-2.3 G) but a correlation between its value and the structure of the aglycone has been noted. Free radicals of that type, stable in aqueous solutions, are potentially interesting for biological studies.     

Tautoméric entre structures α-aleoxy énaminocétone et β-céto iminoéther présentée par les pipéridéines résultant de la semihydrogénation d'alcoxy-2 acyl-3 pyridines

The palladium or platinium-catalyzed partial hydrogenation of some 2-alkoxy-3-acylpyridines has been performed in order to study the tautomerism of the resulting tetrahydropyridines. Reduction of the pyridine ring to tetrahydropyridine occurs selectively for the bicyclic compounds 2 and 3, while predominant reduction of the keto group takes place in the case of the derivative 1 carrying the acyl group in an open chain; this different behaviour towards partial hydrogenation is tentatively explained as a consequence of “I-strain” effect. Whereas the bicyclotetrahydropyridine 6 and 7 present exclusively an α-alkoxy enaminoketone structure, the open chain substituted tetrahydro-pyridine 5 exists only as a β-keto iminoether as shown by ir and proton nmr studies. Total displacement of tautomerism towards one of these two structures is interpreted as the result of the unfavourable interaction of nitrogen and oxygen lone pairs which would occur in a bicyclic iminoether, as compared to the stabilizing interaction of an oxygen lone pair and the N-H bond of the enaminoketone structure, which can be realized without increase of steric crowding in the bicyclic case.     

Étude spectrophotométrique UV. de solutions diluées de chromate dans l'acide sulfurique concentré

Dilute solutions ( < 1· 10^?4M ) of CrO₄K₂ in concentrated sulfuric acid, were investigated spectrophotometrically. Spectral, kinetic and equilibrium studies confirm the instability of Cr^VI species and their conversion to Cr^V complexes, as proposed by MISHRA & SYMONS . Reaction mechanisms are proposed.     

Etude Comparée de la Fragmentation de Trois Composés Médicamenteux a Structure Hétérocyclique: la Primaclone,le Glutethimide et le Phenobarbital

Mass spectra obtained from the three title compounds were compared. High resolution studies and deuterium labelling allowed a proposal for an original cracking pattern, typical of the structure. The postulated mechanism involves a six-centred cyclic electron transfer, generating an aromatic radical ion. Cracking patterns characteristic of barbiturates could also be observed.     

Nouveaux hétérocycles à partir d'esters cyaniques. Arylimino-2 et arylamino-2 4H-benzoxazin-1,3 ones-4, leur tautomérie et étude de leur alkylation régiosélective

New 2-substituted benzoxazinones have been prepared by reaction of primary aromatic amines with aryl cyanates having an ethoxycarbonyl group in the ortho position By ir and nmr studies, a 2-arylimino-4H-1,3-benzoxazin-4-one structure is assigned to their predominant tautomers. The regioselective synthesis of their alkylated derivatives on the cyclic and exocyclic nitrogens by alkylation in ethanol, dimethylformamide and under sloid-liquid phase transfer conditions has been achieved     

Dérivés de désoxy-hydroxylamino-sucres et radicaux libres diglycosylnitroxydes correspondants. Communication préliminaire

Deoxy-hydroxylamino-sugar Derivatives and Corresponding Diglycosylnitroxides Radicals A number of sugar aldonitrones, including C,N-diglycosylnitrones, and ketonitrones have been treated with Grignard reagents or cyanide anion leading to the corresponding deoxy-hydroxylamino-sugars. On oxidation (air, H₅IO₆ or PbO₂), these compounds gave the corresponding nitroxide radicals whose ESR. spectra are reported. Analogues of disaccharides, in which the interglycosidic O-bridge is replaced by a hydroxyimino group, have been obtained by reacting a partially blocked sugar bearing a free hemiacetal group either with a deoxy-hydroxylaminosugar or with hydroxylamine, followed by reaction with an aldehydosugar and a reducing agent (NaBH₄). These reactions represents the key synthetic steps for the oligosaccharide-type synthesis of deoxy-hydroxyimino-oligosaccharides. Their oxidation yielded the corresponding nitroxide radicals whose ESR. spectra gave information on the conformation about the ‘interglycosidic’ bridge. This type of compounds should constitute useful spin markers for biological studies.     

β-Dicéto énamines hétérocycliques: 2. (Pyridyl-4)-2 indanediones-1,3 C-et N-substituées

The authors have studies the regulation of the position of substitution in 2-(4-pyridy)-1-,3-indandiones and the precise methods for introducing functionalised substitutents on teh dihydropyridine nitrogen. These N-substituted compounds can also be synthetised by (a) condensation of momo- or polymethlated pyridines on dialkyl and monoalkyl phthalates and (b) by the oxidative condensation of Nalkylpyridinium btomides on 1,3-indandione. The negative solvatochromy observed in the electronic spectra of the N-substituted 2-(1,4-dihydrp-4-pyridylidèene)-1,3-indandiones leads us to propose a betaïne structure for these compounds.     

Dérivés C-glycosyliques VIII. Synthèse de C-glycosyl-3-pyrazoles à partir d'une nitrilimine dérivée de l'anhydro-2,5-D-ribose. Compétition entre cyclo-additions dipolaires-1,3 et cyclisations non concertés

Several 3-(2,5-anhydro-ribosyl)-pyrazoles of potential medicinal interest have been synthesized by reacting alkynes or alkynylmagnesium bromides with the p-nitrophenylhydrazone of 2,5-anhydro-ribonyl bromide. From a mechanistic standpoint, it has been shown that the sugar-nitrilimine used in these studies reacts more readily as an electrophile than as a dipole. Thus, the hydrazonyl bromide gave exclusively the corresponding phenylethynylhydrazone when treated with phenylethynylmagnesium bromide and led to a 1:1 mixture of phenylethynylhydrazone and pyrazole when reacted with phenylacetylene. This proves that nucleophilic additions onto nitrilimines are much faster than Huisgen's 1,3-dipolar cycloadditions.     

Étude structurale et vibrationnelle de solides moléculaires paramètres cristallins''et spectre d''absorption infrarouge en lumiére polarisée de

X-ray studies indicate that indanone-1 crystals belong to a monoclinic system, space group P2₁/c (C⁵_2h), with the following parameters: a = 7.90±0.01 Å; b = 12.38±0.01 Å; c = 7.39±0.01 Å; β = 99°±30' and Z = 4. A vibrational assignment of fundamental bands observed in the polarized infrared spectrum between 4000 cm⁻¹ and 250 cm⁻¹ is proposed. The band fine structure analysis at 77 °K shows a doublet structure, which agrees with X-ray data.     

Processus de rotation empêchée autour de plusieurs liaisons dans les sels de (N,N-diméthylamino-1 propényl-1-ylidène-3) diméthylammonium

The structural identification of some N,N-dimethyl-aminopropenylylidene-dimethylammonium salts has been achieved by NMR and UV spectrographic studies. Several processes of hindered rotation around C? N and C? C bonds are demonstrated. Free activation enthalpies are determined and discussed in terms of effects of the substituent, anion and solvent.     

Synthèse d'une sonde biotinylée à bras clivable allongé pour l'isolement des récepteurs de l'angiotensine II

Synthesis of a Biotinylated Probe with an Extended Cleavable Arm for Angiotensin II Receptors Purification We have synthesized a new biotinylated probe for angiotensin II receptors studies: biotinyl-NH(CH₂)₂? SS? (CH₂)₂? CO-Gly-? Ahx-[Ala¹, Phe(4N₃)⁸]angiotensin II ( 5 ). This molecule can be photoactivated through an arylazido group. ¹H-NMR studies suggest that it adopts an extended conformation which should allow a simultaneous recognition of both streptavidin and hormone receptor. It has a good affinity for receptors (K_d = 1 nM) and hence is a promising tool in their detection (autoradiography, gold-, ferritin-, enzyme-, or fluorescent streptavidin derivatives) and separation (cell sorting, affinity chromatography). It can be monoiodinated (°6) at its tyrosine residue without a significant loss of affinity. Its extended cleavable arm allows an easy recovery of the ‘probe-receptor’ complex from streptavidin. An HPLC monitoring of the synthesis is described, particularly of the segment coupling 1 + 2 in presence of (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP). This method can be used as well for synthesis of the D -Phe⁸ derivative that has antagonist properties.     

Etude théorique des cycloadditions à partir dM'ylures d'azinium ou de composés homologues

Using a perturbation model the theoretical studies of the title reactions have been carried out and the results compared with experimental data.     

Hétérocyclisations intramoléculaires par réaction d'oxymercuration III. Régiosélectivité et stéréosélectivité de l'oxymercuration intramoléculaire de phénols orthoallyliques

The intramolecular heterocylization of ortho-allylic phenols by oxymercuration has been realized with compounds having different substituents on the allylic chain. In all cases, only the corresponding benzofuran is formed. However, with a substituent at the terminal carbon of the double bond, we also observed the formation of benzopyran. The influence of the solvent and the mercuric salt on the orientation of this reaction has been examined. There is evidence of a molecular rearrangement during the reduction.     

Sur les dérivés de la fluorénone VIII. Difluorénonyl-cétones,difluorényl-cétones et difluorényl-méthanes

By condensation of the chlorides of the four isomeric fluorenecarboxylic acids, respectively of the three 1-, 3- and 4-fluorenonecarboxylic acids with fluorene, followed by reduction of the obtained mono-respectively diketones, the four difluorenylmethanes I, II, III and IV are synthesized. The oxydation of the diketones gives the corresponding triketones. Starting from the chloride of 4-fluorenecarboxylic acid and 1-methylfluorene, a methyl derivative of IV is analogically obtained.     

Stéréosélectivité et régiosélectivité de la réduction des cyclopropènes-2,3 et méthylène-2 cyclopropanes fonctionalisés en position 1

Reduction of 2 cyclopropenyl esters and alcohols with lithium aluminium hydride is selective; at low temperatures (0°) the double bond is not reduced, but at higher temperatures (65°) the reduction is complete and only the cyclopropylmethanol is obtained. The reduction of the double bond is regioselective (the most stable carbanion is formed) and stereospecific (the hydride attack on the double bond occurs cis to the functional group). This stereospecificity can be explained through the initial formation of an alkoxylaluminium hydride followed by an intramolecular reduction of the double bond. Similar results have been obtained in the reduction of functionalised methylenecyclopropanes.     

Dérivés de sucres à groupement gem-dihalogénoéthényle

Carbohydrate Derivatives Bearing a gem-Dihalogenoethenyl Group Treated with the appropriate Wittig reagent, aldehydosugar derivatives ( 1–13 ) led in good to excellent yields to the expected gem-difluoro, gem-chlorofluoro-and/or gem-dichloroenoses ( 14–29 ). Examples of their dibromo analogues had been previously described (see e.g. [1]) but the diiodo derivatives could not be isolated, The influence of the conditions on the yields is reported as well as spectroscopic properties (particularly the long-range ¹³C, ¹⁹F- and ¹H, ¹⁹F-coupling constants) of these new enoses.