Sur l'acylation des méthylfluorènes II [1]. Benzoylation et acétylation du méthyl-2-fluorène

Benzoylation and acetylation of 2-methyl-fluorene according of Friedel-Crafts in carbon disulfide with aluminium chloride yielded the corresponding 7-acylderivatives. By oxydation the benzoyl derivative gave 7-benzoyl-9-oxo-fluorene-2-carboxylic acid, which was decarboxylated to the known 2-benzoyl-9-oxo-fluorene. By reduction according to Clemmensen the acetyl derivative gave 2-methyl-7-ethylfluorene.     

Sur l'acylation des métylfuorènes I. Benzoylation et acétylation du méthyl-1-fluorène

Benzoylation and acetylation of 1-methylfluorene according Friedel-Crafts in carbon disulfide with aluminium chloride yielded the corresponding 2-acyl derivatives. By oxydation the benzoyl derivative gave 2-benzoyl-9-oxo-fluorene-1-carboxylic acid, cyclizable into 1,2-phthalyl-fluorenone.     

Sur l'acylation des méthylfluorènes IV. [1] Benzoylation du méthyl-4-fluorène

Benzoylation of 4-methylfluorene according to Friedel-Crafts in carbon disulfide with aluminium chloride yielded two benzoyl derivatives: 5-methyl-2-benzoyl-fluorene (II) (major product), and 4-methyl-2-benzoyl-fluorene (III). By oxidation II and III gave the corresponding 9-oxo-derivatives, the structure of the last compounds being proved by an independent way.     

Étude thermochimique des méthylnaphtalènes

Calorimetric measurements of enthalpies of change of state (sublimation or vaporization) of methylnaphthalenes gave the following results:

1-methylnaphthalene: (ΔH√_vap)_m=(57.32±0.42) kJ mol⁻¹

2-methylnaphthalene: (ΔH√_sub)_m=(65.69±0.84) kJ mol⁻¹

Combination of these values with those obtained by Speros and Rossini¹ for enthalpies of combustion of these compounds makes it possible to determine their energy of isomerization more accurately. This energy is (2.97±2.41) kJ mol⁻¹ and should be attributed to steric hindrance in the 1-methylnaphthalene molecule.

The comparison of energies of conjugation, theoretical as well as experimental, which we have determine for both molecules studied, confirms the present result.     

Sur l'acylation des méthylfluorènes VI. Formylation du méthyl-2-fluorène et du méthyl-3-fluorène selon Rieche

The formylation of 2-methylfluorene and of 3-methylfluorene according Rieche yields 2-methyl-7-fluorene-carbaldehyde and 3-methyl-2-fluorenecarbaldehyde respectively. The constitution of the obtained aldehydes is proved by their conversion into the known 2,7-dimethyl-fluorene and 2,7-dimethyl-9-fluorenone, respectively into the known 2,3-dimethylfluorene and 2,3-dimethyl-9-fluorenone.     

Synthèse de l'évernine

Synthesis of Evernin Two syntheses of the depside evernin 6 are described. Condensation of methyl acetoacetate and methyl crotonate followed by aromatization and reduction with Raney-Ni led to methyl orsellinate (3) . The condensation of everninic acid (4) , obtained by partial methylation of 3 and saponification of the methyl ester, with methyl 2, 4-dihydroxy-3, 6-dimethylbenzoate (methyl β-orcin carboxylate) (5) in presence of cyclohexylcarbodiimide gave evernin ( 6 ). In a second syntheis methyl dihydroorsellinate (1) was regiospecifically converted into its 4-methyl enol ether and aromatized via the benzene selenenyl derivative to yield methyl evernate (7) . Benzylation followed by saponification gave the free acid 8 . Methyl β-orcin carboxylate (5) was synthesized in an analogous way from methyl 3,6-dimethyl-2,4-dioxocyclohexanecarboxylate. Condensation of 8 with the methyl ester 5 by treatment with trifluoroacetic anhydride in toluene yielded 9 , which could be converted into evernin ( 6 ) by hydrogenolysis of the benzyl ether.     

Fluorénacènes et fluorénaphènes synthèses dans la série des indéno-fluorènes,XVII. Dérivés méthylés du cis-fluorénacène,du trans-fluorénacène et du trans-fluorénaphène

By condensation of the chlorides of the three 9-oxo-fluorene-2-, -3-, and -4-carboxylic acids with 4-bromo-1,2-xylene on one side, and of the chlorides of o-bromobenzoic acid, 2-bromo-4-methyl-benzoic acid and 2-bromo-4,5-dimethyl-benzoic acid with fluorene, 2-methylfluorene and 3-methylfluorene on the other side, followed by direct or indirect cyclisation and by final reduction, several new methyl derivatives of the indenofluorenes I, II and IV are synthesized.     

Fluorénacènes et fluorénaphènes Synthèses dans la série des indéno-fluorènes XIV [1] Nouvelle synthèse du trans-fluorénacène

A new synthesis of 6, 12-dihydro-indeno [1,2-b] fluorene (trans-fluorenacene) in 9 steps starting from fluorene (overall yield 24,5%) is recorded. By partial oxidation of the hydrocarbon its 6-oxo derivative is also obtained.     

Action d'organolithiens sur la méthyl-2 quinoxaline. Etude de la réactivité des adduits

The action of organolithium reagents such as phenyllithium or n-bulyllithium on 2-methylquinoxaline gave lithiation of the methyl group which upon reaction with electtropholesphiles produce side chain alkenyl derivatives. On the other hand organolithium reagents react with the quinoxaline azomethine bond to give I-lithio-2-alkyl)or ary-1)-3 methylquinoxalines which can be further loithiated on the methyl group to give 2-alkyl(or aryl)-3-alkenylquinoxaline derivatives. The adducts can be condensed with clectrophiles such as benzonitrile or methlyl benzoate but only methyl benzoate leads to N condensed derivatives. Furthermore substituted 1,2,3,4-terahydroqinoxalines are available via the above lithio intermediates.     

Synthèses dans la série des bis-indéno-fluorènes,IX. Le dihydro-13,15-7H-bis-indéno[2.1-b; 2′.1′-h]fluorène et son dérivé méthylé en position 6

By condensation according Ullmann of 2-iodo-9-oxo-fluorene with 3-bromo-2-cyano-9-oxo-fluorene, followed by cyclisation and reduction, the new linear 13,15-dihydro-7H-diindeno[2.1-b; 2′.1′-h]fluorene (III) is synthesized in 3 steps. The 6-methyl-derivative of II is also obtained in a similar way.     

Hétérocycles à fonction quinone. 10. Synthèse et activité cytotoxique de la (diamino-2,4 pyrimidinyl-5)-6 méthoxy-2 naphtalènedione-1,4

Cycloaddition of guanidine to a α-cyaanoketene-S,S-diacetal gave the pyrimidine ring of the 6-(2,4-diamino-5-pyrimidinyl0-2-methoxy-1, 4-naphthalendeione ( 14 ). The quinonoid function was obtained by oxidation of the corresponding primary amine by potassium nitrosodisulfonate (Fremy's reagent). The cytotoxicity of this quinone is promising.     

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.     

Dérivés C-Glycosyliques XXXII. Synthèse de dérivés spiro-C-glycosylidéniques par cyclisation nucléophile. Communication préliminaire

C -Glycosylic derivatives XXXII. Synthesis of spiro-C -glycosylidenic derivatives via nucleophilic cyclization. On treatment with compounds bearing two nucleophilic groups as ethylenediamine, o-phenylenediamine or their monooxa or monothia analogues, 1,2:5, 6-di-O-isopropylidene-α-D -ribo-hexofuranos-3-ulose gave with excellent yields the corresponding spiro-C-glycosylidenic derivative; for example, when using o-phenylenediamine, a spirobenzimidazoline ( 5 ) was obtained. The latter compound underwent, on oxidation, a ring expansion to a morpholinobenzimidazole ( 8 ). Spirobenzodiazepines, spirobenzooxazepines and spirobenzothiazepines were formed when applying the same type of cyclization reaction to 3-C-acetylmethylene-3-deoxy-1,2:5,6-di-O-isopropylidene-α-D -ribo- and α-D -xylo-hexofuranoses.     

Synthèse de céphalosporine-lactones

Condensation of azetidinones 2a and 2b with mercaptan 3 gave respectively compound 10 or a 1:1 mixture of 17 and 17 ′. Bromination of 10 , afforded cis and trans-bromohydrins 13a and of 17 and 17 ′ cis and trans-bromohydrins 18a . Acetylation and reduction with zinc and acetic acid of these bromohydrins gave cephems 4a or 4b and 4b ′ respectively.     

Synthesis, reactions and antimicrobial activities of 8-ethoxycoumarin derivatives

Condensation of 3-acetyl-8-ethoxycoumarin (3) with thiosemicarbazide gave ethylidenehydrazinecarbothioamide 5, which was transformed into the thiazolidin-4-one derivatives 6,7. Interaction of 3 with DMF/POCl(3) gave b-chloroacroline derivative 8. Treatment of 3 with malononitrile gave benzo[c]chromone and 2-aminobenzonitrile derivatives 9 and 10, respectively with respect to the reaction conditions. Condensation of 3-(2-bromoacetyl)-8-ethoxycoumarin (4) with o-phenylenediamine gave 3-(quioxaline-2-yl)-8-ethoxycoumarin hydrobromide (11), while 4 reacted with 2-aminopyridine to give chromenopyridopyrimidine derivative 12. Condensation of 4 with potassium thio-cyanate/methanol gave an unexpected derivative, 2H-chromeno-3-carboxy(methyl-carbonimidic)thioanhydride 16, which upon treatment with (NH(2))(2)·H(2)O gave 3-ethoxy-2-hydroxybenzaldehyde azine 19. Interaction of 4 with thiourea derivatives gave thiazole derivatives 20a-c. The structures of the newly synthesized compounds were confirmed by their spectra data. The newly synthesized compounds were also screened for their antimicrobial activity.     

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.     

Structure cristalline et moléculaire d'un dérivé méthyl-hexopyranoside à C(4) hybridé sp2

The derivative C₁₃H₁₉NO₅ crystallizes in space group P2₁2₁2₁ with a = 9.371, b = 11.815, c = 13.207 Å and Z = 4. The structure was solved by direct methods and refined by full-matrix least-squares to R = 0.058. The pyranose ring exists in the ³S₁ conformation (or in the equivalent, but here structurally less consistent, ⁰S₄ conformation). The dioxolane ring has an envelope conformation. Strong intramolecular interactions between the bulky substituents suggest that the ensuing strain energy is assumed, for a significant part, by the twisted-boat conformation of the pyranose ring.     

Dérivés d'énose- et d'ynosephosphonates et composés voisins. Communication préliminaire

Derivatives of enose- and ynosephosphonates and related compounds. Preliminary communication The gem-dibromo terminal enoses 1 and 7 are convenient sources of glycosylacetylenes which upon reaction with phosphorus electrophiles gave the phosphorusbearing acetylenic sugars 4, 5 and 8 . Compounds 5 and 8 underwent cycloaddition reactions leading to isoxazolyl-C-glycosides 6 and 9 respectively. The nitroolefinic sugar derivative 11 gave upon bromination-dehydrobromination the first example of a new kind of potentially useful synthetic intermediates, the gem-bromonitroenose 12 . The enosephosphonate 13 was also prepared from 11 . The diglycosylhydroxylamine 18 represents another type of phosphorus-bearing acetylenic sugar derivative. Some ¹H- and ¹³C-NMR. data relative to the new types of phosphorus-containing sugar derivatives synthesized are given.     

Recherches en série triazepine-1,2,4: 1 - détermination de la structure de la triazolotriazépinone obtenue par action de l'acétylacétate d'éthyle sur le diamino-3,4 triazole-1,2,4

The condensation of 3,4-diamino 1,2,4-triazole with ethyl aceloacelate gave 6-methyl-8,9-dihydro(7H)-s-triazolo[4,3-b]-1,2,4-triazepin-8-one ( 2 ); 2 has been caracterized by nmr spectroscopy and by comparison with its methylated derivative prepared in an unambigous manner.     

Etude dans la série des pyrrolidinones. IV. Formation de quelques dérivés de l'acide L méthylène bis N-(oxo-5 pyrrolidine carboxylique-2)

Starting from the readily available 5-oxo-2-carboxypyrrolidine, methylene-bis-(N-5-oxo-2-carboxypyrrolidine) was prepared and transformed into a diamine, then into two isomeric diols, which cyclised into one ether. The meso configuration has been assigned for this ether. The reduction of both diols and ether was complete and gave rise to methylene-bis-N-pyrrolidine.