Réactivité de l'hypochlorite de tertiobutyle dans l'oxydation du benzothiophene

In reaction with benzothiophene, t-butyl hypochlorite acts as an oxidizing reagent and a chlorination reagent. A mixture of 3-ehlorobenzothiophene, three 2,3-dichloro-2,3-dihydrobenzothio-phene 1-oxide isomers (trans-anti: trans-syn; cis-anti) and 2-chlorobenzothiophene 1-oxide was obtained. With a large exces of t-butyl hypochlorite, the reaction leads to 2,3-dichlorobenzothio-phene, 2,3-dichlorobenzothiophene 1-oxide. 2,2,3-trichloro-2,3-(lihydrobenzothiophene 1-oxide and 2,3-dichloro-3-oxobenzothio-phene 1-oxide. In any case, oxidation stops at the level of the sulfoxide.     

Alkylation en catalyse par transfert de phase d'une série d'acridanone-9 substituées: Compétition entre O- et N-alkylation

Substituted acridanones were alkylated under phase transfer catalysis conditions. In so doing, a mixture of O- and N-alkyl derivatives was prepared. Orientation of the reaction products depends upon the alkylating agent but not on the position of the substituent. Hence, HSAB principles can explain this orientation.     

Syntheses and Crystal Structures of 2,7‐Di(trimethylsilyl)thieno[3,2‐e]benzothiophene, 1,2,5,6(5)‐Tetra(trimethylsilyl)‐1,2,5,6(2,3)‐tetrathiophenacyclooctaphan‐3(z),7(z)‐diene,and 2,7‐Di(trimethylsilyl)thieno[3,2‐e]benzothiophene‐4‐ol

With 5,5′‐di(trimethylsilanyl)‐3,3′‐bithiophenyl‐2,2′‐dicarbaldehyde as precusor, 2,7‐di(trimethylsilyl)‐thieno[3,2‐e]benzothiophene was obtained effiently via intramolecular McMurry reaction. At the same time, another two unexpected compounds, 1,2,5,6(5)‐tetra‐(trimethylsilyl)‐1,2,5,6(2,3)‐tetrathiophena‐cyclooctaphan‐3(Z),7(Z)‐diene and 2,7‐di(trimethylsilyl)thieno[3,2‐e]‐benzothiophene‐4‐ol were generated as side products. The crystal structures of all three title compounds are described.     

Synthèse de sucres aminés ramifiés III. Synthèse et réactions de 1′α-amino-nitrile dérivé du di-O-isopropylidène-1,2:5,6-α-D-ribo-hexofurannosul-3-ose

The addition of cyanohydric acid to 1,2:5,6-di-O-isopropylidene-α-D -ribo-hexofurannos-3-ulose can be sterically controlled. Under kinetic conditions, the allo cyanohydrine epimer is formed, under thermodynamic conditions, the gluco epimer is formed. The configuration of these two products is proved by their chemical reactions. Hydration followed by hydrolysis of the nitrile group of the allo epimer (O-acetyl derivative) gives the 3-C-carboxy-1,2-O-isopropyloidene compound. This product forms the corresponding γ or δ-lactone with hydroxyl ( 5 ) or ( 6 ). On the other hand, after hydrolysis of 5,6-isopropylidene, the 3-O-acetyl derivative of the gluco epimer gives an acetyl migration from position 3 to position 5 and finally to position 6. By reaction of the allo epimer with NH₃ and CN^?, an aminonitrile is formed. The allo configuration is deduced from the above mentioned reaction and from IR. and NMR. data. Several acetylated and trifluoracetylated derivatives of these products are described. The oxidation of the nitrile group to the amide group is possible with both epimeric cyanohydrines and the amino-nitrile.     

C-Glycosides,IV. Mise en évidence d'un mécanisme concurrent de la cyclo-addition dipolaire-1,3 concertée lors de la réaction d'une azométhine-imine avec un dipolarophile acétylénique. Communication préliminaire

The reaction of a glycosyl-azomethine imine with an acetylenic dipolarophile in the usual conditions for 1, 3-dipolar cycloaddition led to an α-ethynyl-hydrazone beside the ‘normal’ product of the reaction, i.e. the corresponding pyrazole. Deuteration experiments indicated that the two products are formed by two concurrent independent pathways. It is supposed that the slow step in the formation of the α-acetylenic hydrazone is the ionization of the alcyne whose conjugated base reacts rapidly with the 1, 3-dipole.     

Etudes stéréochimiques XIV. Adduits de Diels-Alder en série résiniques; action des peracides et ouvertures acido-catalysées d'époxydes

Studies in Stereochemistry XIV. Diels-Alder adducts in the resin series; action of peracids and acid-catalysed ring opening of epoxides The synthesis of Diels-Alder compounds of type 2 with a 17-nor-13(14)-atisène skeleton is described (cf. Schemes 1–3). Depending on the nature and configuration of substituents R¹ and R² on the carbon atoms 15 and 16, an epoxide ( 24–33 ) or a ketone ( 35–38 ) or a mixture of epoxide, ketone and lactone is obtained by the action of p-nitroperbenzoic acid on the double bond of these adducts (cf. Scheme 4). A simplified reaction scheme is suggested to explain the formation of the various products. In an acid-catalysed reaction, the epoxides isomerize mainly into ketones. Nevertherless, in some cases, dienes (e.g. 52 ) or hydroxy-γ-lactones of (13R*, 14S*)-configuration (e.g. 50 ) resulting from the opening of the epoxide ring with retention of configuration were obtained.     

Acylation des β-énaminoesters: Regio et stéréoformation des β-énaminoesters N- ou C-acylés

The reaction of acyl chlorides with cyclic five-membered β-enaminoesters gave exclusively N-acylated products while reaction of acyl chlorides with cyclic seven-membered β-enaminoesters gave only C-acylated products. In the case of cyclic six-membered β-enaminoesters, the reaction of acyl chlorides gave a mixture of N-acylated and C-acylated products.     

Recherche d'analogues de nucléosides à activité antivirale

Search for Antiviral Nucleosides Analogues In contrast to the reported impossibility of obtaining the expected products when 1-(2,3-O-isopropylidene-1,5-dialdoribofurannos-1-yl)uracile ( 2 ) was treated with stabilized ylides, we prepared in good to excellent yields the modified nucleosides 4–9 by reaction of 2 respectively with acetylmethylidene-, benzoylmethylidene-, ethoxymethylidene-, methoxymethylidene-, succinimidylidene- or N-phenylsuccinimidylidene-triphenylphosphorane. Compounds 4–10 were tested against the herpes virus type 1 (HF) and influenza virus A₂/Scotland. The modified nucleoside 9 showed a limited but significative activity against the herpes virus.     

Dimethyl Carbonate as a Sacrificial Molecule for the Synthesis of 5‐Memebered N‐ and O‐Heterocycles

In the last twenty years DMC has been employed as an efficient methylating and methoxycarbonylating agent with several monodentate and bidentate nucleophiles, showing great selectivity and unexpected results. In this short review we report on yet another application of DMC chemistry i.e. the synthesis of 5‐membered N‐ and O‐heterocycles. In these reactions DMC acts as a sacrificial molecule since it is not present in the final products, but only in the reaction intermediates as an halogen‐free leaving group. This DMC‐based synthesis of heterocycles resulted of general application, as it is effective for aliphatic and aromatic 1,4‐diols, incorporating several functionalities (primary, secondary, tertiary, allylic, phenolic), as well as, for bifunctional compounds i.e. 4‐amino‐1‐butanol. This synthetic procedure was also employed for industrially relevant compounds such as (‐)‐norlabdane oxide and isosorbide showing to maintain the chiral integrity of the substrate. In one case intramolecular cyclisation of isosorbide was also observed to achieve a strained tricyclic derivative. Comparing this reaction methodology with a chlorine based procedure, the DMC‐mediated pathway is quantitative, occurs in one step, does not require any chlorine‐based chemical or strong acid and does not produce any chlorinated waste material.     

Quelques réactions nuclé ophiles et électrophiles de la thiéno[2,3-b]pyrazine. Comparaison de sa réactivite avec celles de thiéno diazines et de la thiényl-2 pyrazine dans le cas de la nitration

We studied the action of nbutyllithium, the action of chlorine and the action of nitric acid in sulfuric acid medium on thieno-[2,3-b]pyrazine, These reactions led us to comparethe behaviour of thieno[2,3-b]pryazine with that of thieno[2,3-d]pyrimidine and of thieny1-2pyrazine under the same consitions.     

Régiospécificité de la cycloaddition des diarylnitrilimines sur quelques dérivés indoliques

In this paper, we describe the results of a study of the reaction of diaryl nitrilimines with N-ethylindole ( 1 ) and 2-methoxycarbonyl-N-ethylindole ( 2 ). The regioselectiivity of the reaction is reversed when going from 1 to 2 as it has been spectroscopically and chemically demonstrated.     

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.     

Application de la réaction de Wittig à la synthèse de dérivés de bromoénosuloses et d'esters bromoénuroniques. Note de laboratoire

Use of the Wittig reaction for the synthesis of derivatives of bromoenosuloses and bromoenuronic esters Treatment of 3-O-benzyl (or 3-O-methyl)-1, 2-O-isopropylidene-α-D -xylo-pentodialdo-1, 4-furanoses ( 2 or 1 ) with acetylbromomethylidenetriphenylphosphorane ( 3 ), benzoylbromomethylidenetriphenylphosphorane ( 4 ) or bromoethoxycarbonylmethylidenetriphenylphosphorane ( 5 ) gave in good to excellent yields the expected enose ( 6--11 ). In all cases but one ( 8 where some 10% of the E-isomer was formed) the reaction led to the exclusive formation of the Z-isomer whose configuration was established by NMR.     

Diénamines hétérocycliques. III. Réexamen de la réaction de la base de Fischer avec le tétracyanoéthylène

Heterocyclic dienamines III. A re-examination of the reaction of Fischer's base on tetracyanoethylene Depending on the order of addition, Fischer's base 5 (1,3,3-trimethyl-2-methylidene-indoline) reacts 1:1 with tetracyanoethylene to give either the tricyanovinylation product 6 or the spiro compound 7 . A skeletal rearrangement of a zwitterionic intermediate can explain the formation of the spiro compound. The latter undergoes a thermal isomerization yielding by ring expansion the tetrahydroquinoléine 8 . On reaction with LiAlH₄ or CH₃ONa 7 and 8 lead both to triazatetracycles. All structures are assigned on the basis of spectral data.     

Dérivés de sucres benzimidazoliques et benzothiazoliques

Benzimidazole and benzothiazole sugar derivatives Simple aldehydosugars such as 1 or 2 , by reaction with o-phenylenediamine, gave the corresponding benzimidazoles 3 and 4 . Whereas the unperturbed α, β-unsaturated aldehydosugar D gave the benzodiazepine E upon treatment with o-phenylenediamine, the formyl-bearing alkenyl acetals 5 and 8 led, in the same conditions, to the benzimidazoles 6 and 9 respectively or, on reaction with o-aminothiophenol, to the benzothiazoles 7 and 10 respectively. This difference in reactivity is explained by the electrondonor ability of the oxygen atom of the alkenyl acetal function as shown by the ¹³C-RMN. spectra.     

Synthèse par cyclisation nucléophile de dérivés de sucres portant un hétérocycle inséré en spiro. Note de Laboratoire

Synthesis of Sugar Derivatives Bearing a Spiro Heterocycle via Nucleophilic Cyclization Treated with the 1,4-binucleophiles 1,2-diaminoethane, 2-aminoethanol, 2-aminoethanethiol, L -cysteine, o-phenylenediamine, o-aminophenol or o-aminothiophenol the ketosugar derivative 1 gave in good yields the corresponding spiro derivatives 2–8 . In each case, the reaction was stereospecific leading to the isomer bearing the N-atom on the endo face of the bicyclic starting material. Starting from the sugar enone 9 , the aromatic 1,4-binucleophiles led stereospecifically to the spirobenzo [b]-diazepine 10 , -oxazepine 11 or -thiazepine 12 . In one case, an imine (13) was isolated. As 13 cyclized to 6 , the intermediate formation of these kind of derivatives could be considered as a common step for all these reactions.     

RMN 13C de cyclanones halogénées. Détermination et additivité des incréments du chlore en série cyclohexanique

The ¹³C n.m.r. spectra of fourteen chlorocyclohexanones have been recorded to examine the variation of the ¹³C chemical shifts as a function of the position and the number of the chlorine substituents. Additivity relationships were found which enable reasonable prediction of the chemical shifts of chlorinated cyclohexanones. Comparison between the observed and calculated chemical shifts of mono- and dichlorinated flexible molecules shows that the chlorine effects are additive.     

Préparation de phosphonates de sucres ramifiés par addition nucléophile conjuguée. Communication préliminaire

Preparation of unsaturated sugars phosphonates using nucleophilic conjugate addition Different types of phosphorus nucleophiles underwent conjugate addition reaction with one of the branched-chain sugars 4, 5 or 11 the addition taking place either on the endo or the exo face of the furanose ring (or on both faces in the case of 11 ). The configuration at C(3) of these new phosphorus-bearing types of sugars as well as the configuration at the phosphorus atom of the cyclic phosphinates 9 and 10 was established by NMR. (³J_P,H–C(2), ³J_P,C(1)). Small amounts (7%) of the spiro enol phosphonate 16 were formed when 11 reacted with trimethyl phosphite.     

Dérivés C-glycosyliques. VII. Synthèse et réactions de nitrones dérivées de sucres. Communication préliminaire

The syntheses of three types of sugar nitrones (aldonitrone, ketonitrone and α-β unsaturated aldonitrone) are described. On 1,3-dipolar cycloaddition with phenylacetylene, the aldonitrone gave two Δ₄-isoxazolines epimeric at the new asymetric carbon, while the same reaction on the ketonitrone led to a spiro-Δ₄-isoxazoline. The reaction of these nitrones with carbon nucleophiles like phenylethynylmagnesium bromide constitutes a novel chain-extension reaction in carbohydrate chemistry.     

Photochimie d'hétérocycles azotés. IV. Transposition de type photo-fries des N-acétyl benzimidazolones

The photolysis of benzene or alcoholic solutions of N-acetyl-and N,N-diacetylbenzimidazolones gave mixtures of ortho- and para-rearrangements products accompanied to some extent with de-N-acylation. The different products have been identified by means of nmr, mass spectrometry and unambiguous synthesis.