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.     

Sur les dérivés de la fluorénone VI Les acides bromo-3-fluorénonecarboxylique-2 et bromo-2-fluorénonecarboxylique-3 et la bromo-3-méthyl-4-fluorénone

Starting from 2-amino-3-bromo-9-oxofluorene and from 3-methylfluorene respectively the preparation of 3-bromo-9-oxofluorene-2-carboxylic acid and of 2-bromo-9-oxofluorene-3-carboxylic acid is described. A synthesis of 3-bromo-4-methyl-9-oxofluorene is also given.     

Synthèse énantiospécifique de la (+)-(R)-éthyl-6-dihydro-2,3-méthyl-2-4H-pyranone-4, phéromone de la mite Hepialus hecta L

Enantiospecific Synthesis of (+)-(R)-6-Ethyl-2,3-dihydro-2-methyl-4H-pyran-4-one, Sex-pheromonal Component of the Male Swift Moth Hepialus hecta L . A new synthesis of (+)?(R)-6-ethyl-2,3-dihydro-2-methyl-4H-pyran-4-one ((R)- 8 ), sex-pheromonal component of the male swift moth Hepialus hecta L., has been performed from (?)-(R)-1-(1,3-dithian-2-yl)propan-2-ol with an enantiomeric excess of ? 97%.     

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.     

Quantum chemical study of the transformation of 2-(N-alkylamino)-3-(indol-1-yl)-and 2-(N-alkylamino)-3-(indol-3-yl)maleimides by protic acids: Tandem hydride transfer/cyclization mechanism

The geometric parameters, the charge distribution, and the energetics of N-methyl-2-(N-ethylanilino)-3-(indol-1-yl)-and N-methyl-2-(N-ethylanilino)-3-(indol-3-yl)maleimides and their conjugated acids were studied by density functional theory calculations at the B3LYP/6-31G(d) level. The mechanism of the tandem hydride transfer/cyclization sequence, which occurs after protonation of N-methyl-2-(N-ethylanilino)-3-(indol-1-yl)-and N-methyl-2-(N-ethylanilino)-3-(indol-3-yl)maleimides, was analyzed. The investigation of the potential energy surface for the tandem hydride transfer/cyclization of the iminium cation that formed upon protonation revealed that the hydride transfer followed by intramolecular cyclization at position 7 of the indole fragment in N-methyl-2-(N-ethylanilino)-3-(indol-1-yl)maleimide is the preferable process, unlike alternative intramolecular cyclization involving the cationic center at the C(2) atom of the indole fragment and the benzene ring of the N-ethylaniline fragment of the indoleninium cation in N-methyl-2-(N-ethylanilino)-3-(indol-3-yl)maleimide. A study of the key intermediates of the assumed reaction mechanism demonstrated that these intermediates are actually stationary points on the potential energy surface (minima and transition states). Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2069–2073, December, 2006.     

Synthèse énantiospécifique des acides (+)-(2R)- et (−)-(2S)-éthyl-6-dihydro-3,4-méthyl-2-oxo-4–2H pyranecarboxylique-5

Enantiospecific Synthesis of (+)-(2R)- and (?)-(2S)-6-Ethyl-3,4-dihydro-2-methyl-4-oxo-2H-pyran-5-carboxylic Acid The two enantiomers (?)-(2S)- and (+)-(2R)-6-ethyl-3,4-dihydro-2-methyl-4-oxo-2H-pyran-5-carboxylic acid ((S)- and (R)- 7 ) have been synthesized from (+)-(3S) and (?)-(3R)-3-hydroxybutanoates, respectively (Scheme 1). By reduction and decarboxylation, the tetrahydro-2H-pyranols (2R, 4R, 6S)- and (2S, 4S, 6R)- 13 , respectively, were obtained with an enantiomeric excess of ≥ 93%.     

Isomerès optiques du naftidrofuryl ( = 2-[(naphth-1-yl)méthyl]-3-(tétrahydrofur-2-yl)propanoate de 2-(diéthylamino) éthyle)

Optical Isomers of Naftidrofuryl( = 2-(Diethylamino)ethyl 2-[(Naphth-1-yl)methyl]-3-(tetrahydrofur-2-yl)propanoate) The four optical isomers of naftidrofuryl ( 1 ) were prepared in two ways, by separation and resolution of the two diastereoisomeric racemates and by synthesis from the enantiomers of tetrahydrofuran-2-methanol ( 6 ); see Scheme}. The absolute configuration of one of the isomer as a tartrate monohydrate was established by X-ray crystallography thus allowing the deduction of the absolute configurations of the other three optical isomers.     

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.     

Sur l'acylation des méthylfluorènes III [1]: Benzoylation et acétylation du méthyl-3-fluorène

Benzoylation and acétylation of 3-methyl-fluorene according to Friedel-Crafts in carbon disulfide with aluminium chloride yielded the corresponding 2-acyl derivatives. By oxidation the benzoyl derivative gave 2-benzoyl-9-oxo-fluorene-3-carboxylic acid, cychsable into the known 2,3-phthalyl-fluorenone. By Clemmensen reduction, the acetyl derivative gave 3-methyl-2-ethyl-fluorene.     

Products from furans. VI. Synthesis of dihydro-2-disubstituted-2H-pyran-3(4H)-ones,tetrahydro-3-(aminomethyl)-2-(p-methoxyphenyl)-2-methyl-2H-pyran-3-ol derivatives and 6-(p-methoxyphenyl -6-methyl-7-oxa-1,3-diazaspiro[4,5]decane-2,4-dione

Hydrogenolysis of 5,6-dihydro-6-(p-methoxyphenyl)-6-methyl-5-oxo-2H-pyran-2-yl ethyl carbonate yielded dihydro-2-(p-methoxyphenyl)-2-methyl-2H-pyran-3(4H)-one, 3 . Subsequently cyanohydrin 4 , derived from 3 , on reduction afforded 3-(aminomethyl)tetrahydro-2-(p-methoxyphenyl)-2-methyl-2H-pyran-3-ol, 5 . The synthesis of N-dimethyl,N-isopropyl,N-imidazolyl as well as N-oxazolinyl derivatives of 5 is presented. The synthesis of 6-(p-methoxyphenyl)-6-methyl-7-oxa-1,3-diazaspiro[4,5]decane-2,4-dione 10 , a spiro hydantoin prepared from ketone 3 is also reported.     

Amine-induced rearrangements of 2-bromo-1-(1H-indol-3-yl)-2-methyl-1-propanones: A new route to α-substituted indole-3-acetamides, β-substituted tryptamines, α-substituted indole-3-acetic acids and indole β-aminoketones

The reaction of 2-bromo-1-(1H-indol-3-yl)-2-methyl-1-propanone ( 1 ) and 2-bromo-1-(1-methyl-1H-indol-3-yl)-2-methyl-1-propanone ( 2 ) with primary amines proceeds in good yields to produce rearranged amides by a proposed pseudo-Favorskii mechanism. These amides in turn can either be reduced to produce β-substituted tryptamines or hydrolyzed to produce substituted indole-3-acetic acids. When the reaction is carried out using bulky primary or secondary amines, β-aminoketones are produced by elimination of hydrogen bromide followed by Michael addition. When hindered secondary amines or tertiary amines are used, elimination to the α,β-unsaturated ketones occurs.     

Synthesis of lithium,sodium, cesium,and calcium salts of (E)-4- or (E,S)-3-methyl-2-(5-arylisoxazol-3-yl)-methyleneaminobutanoic, (E,S)-4-methyl-2- or (E,2S,3S)-3-methyl-2-(5-arylisoxazol-3-yl)methyleneaminopentanoic,and (E)-6-(5-arylisoxazol-3-yl)methyleneaminohexanoic acids

Preparative method for the synthesis of lithium, sodium, cesium, and calcium salts of (E)-4-(5-arylisoxazol-3-yl)methyleneaminobutanoic, (E)-6-(5-arylisoxazol-3-yl)methyleneaminohexanoic, (E,S)-3-methyl-2-(5-arylisoxazol-3-yl)methyleneaminobutanoic, (E,S)-4-methyl-2-(5-arylisoxazol-3-yl)methyleneaminopentanoic and (E,2S,3S)-3-methyl-2-(5-arylisoxazol-3-yl)methyleneaminopentanoic acids was developed by reacting 5-phenyl(4-tolyl)isoxazole-3-carbaldehydes with amino acids like 4-aminobutyric and 6-aminocaproic acids, L-valine, L-leucine or L-isoleucine in the presence of lithium hydride, sodium methoxide, cesium carbonate or calcium hydride in boiling methanol.     

Reaction of 2-(phenylamino)benzoic and 2-(phenylamino)- and 2-methyl-6-phenylpyridine-3-carboxylic acid hydrazides with succininc anhydride

Reactions of 2-(phenylamino)benzoic and 2-(phenylamino)- and 2-methyl-6-phenylpyridine-3-carboxylic acid hydrazides with succinic anhydride in organic solvents at room temperature gave the corresponding 4-(2-aroylhydrazinyl)-4-oxobutanoic acids. The reactions in boiling acetic acid afforded N-(2,5-dioxopyrrolidin-1-yl)benzamide or N-(2,5-dioxopyrrolidin-1-yl)pyridine-3-carboxamide.     

Synthesis of 1-[3-methyl-2(3H)-benzazolon-5- or 6-yl]-4-{4-[cis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl-methyl)-1,3-dioxolan-4-yl]methyleneoxyphenyl}piperazines

Reactions of 3-methyl-6-[4-(4-hydroxyphenyl)-1-piperazinyl]-2(3H)-benzoxazolone, 3-methyl-6-[4-(4-hydroxy-phenyl)-1-piperazinyl]-2(3H)-benzothiazolone and 1,3-dimethyl-5-[4-(4-hydroxyphenyl)-1-piperazinyl]-2(3H)-benzimidazolone with cis-{[2-(2,4-dichlorophenyl) -2-(1H-imidazol-1-ylmethyl)]-1,3-dioxolan-4-yl}methyl meth-anesulfonate in the presence of sodium hydride furnish the title compounds.     

Synthesis of Derivatives of 4-Hydroxy-2-methyl-3-[2-(5-mercapto-1H-1,2,4-triazol-3-yl)ethyl]quinoline and 2-[2-(4-Hydroxy-2-methyl-3-quinolyl)ethyl]-4H-3,1-benzoxazin-4-one

From 4-hydroxy-2-methylquinoline-3-propionyl chlorides hydrochlorides the corresponding thiosemicarbazides were synthesized. The cyclization of the latter both in alkaline and acidic media furnished 4-hydroxy-2-methyl-3-[2-(5-mercapto-1H-1,2,4-triazol-3-yl)ethyl]quinolines. The reaction of the above propionyl chlorides with anthranilic acid afforded the corresponding 2-[2-(4-hydroxy-2-methyl-3-quinolyl)ethyl]-4H-3,1-benzoxazin-4-ones.     

Synthesis and tuberculocidic activity of some 4-arylaminomethylene-3-methyl-1-(pyrimidin-2-yl)pyrazol-5(4H)-ones

4-Arylaminomethylene-3-methyl-1-(6-methyl-4-oxo-1,4-dihydropyrimidin-2-yl)pyrazol-5(4H)-ones were synthesized by a three-component reaction between the 6-methyl-2-(3-methyl-5-oxo-2,5-dihydropyrazol-1-yl)pyrimidin-4(1H)-one, triethoxymethane, and an aromatic amine. These compounds were found to exist as aminomethyleneketones regardless of the electronic effects of substituents in the aromatic fragments. The resulting compounds showed pronounced tuberculocidic activity.     

Stereospezifität der neuroleptischen Wirkung und Chiralität von (+)-3-{2-[4-(8-Fluor-2-methyl-10,11-dihydrodibenzo[b,f]thiepin-10-yl)-1-piperazinyl]-äthyl}-2-oxazolidinon (16). 4. Mitteilung über tricyclische Antidepressiva und Neuroleptica

Stereospecifity of the neuroleptic activity and chirality of (+)-3-{2-[4-(8-fluoro-2-methyl-10, 11-dihydrodibenzo[b,f]thiepin-10-yl)-1-piperazinyl]ethyl}-2-oxazolidinone (16). The synthesis and stereospecific neuroleptic action in animals of the (+)-enantiomer of 3-{2-[4-(8-fluoro-2-methyl-10,11-dihydrodibenzo [b,f]thiepin-10-yl)-1-piperazinyl]ethyl}-2-oxazolidinone ( 16 ) are briefly described. The (10S)-configuration of this compound was determined by X-ray diffraction.     

Transformations of 2-(3-Hydroxy-3-methyl-1-butynyl)adamantan-2-ol >Catalyzed by Acids

Reaction of 2-(3-hydroxy-3-methyl-1-butynyl)adamantan-2-ol with acetonitrile under Ritter reaction conditions is accompanied by isomerization and partial hydration where the water addition to the triple bond occurs nonselectively. As a result of reaction carried out in the presence of 8 equiv of sulfuric acid a mixture was obtained of N ²-[4-(1-acetylamino-2-adamantyl)-2-methyl-3-butyn-2-yl]acetamide, N ³-[1-(1-acetylamino-2-adamantyl)-3-methyl-2-oxo-3-butyl]-acetamide, and N ³-[1-(1-acetylamino-2-adamantyl)-3-methyl-1-oxo-3-butyl]acetamide in ~10:3:2 ratio. In the presence of 2 equiv of the acid the mixture obtained consisted of N ²-[4-(1-acetylamino-2-adamantyl)-2-methyl-3-butyn-2-yl]acetamide, N ³-[1-(1-acetylamino-2-adamantyl)-3-methyl-2-oxo-3-butyl]acetamide, and 1-(1-acetylamino-2-adamantyl)-3-methyl-2-buten-1-one in the same ratio. In Rupe reaction conditions we obtained instead of the expected ,-unsaturated ketones a mixture of 1-(1-hydroxy-2-adamantyl)-3-hydroxy-3-methylbutan-1-one and 1-(1-hydroxy-2-adamantyl)-3-hydroxy-3-methylbutan-2-one in a 5:3 ratio.     

5-(α-Fluorovinyl)tryptamines and 5-(α-Fluorovinyl)-3-(N-methyl-1′,2′,5′,6′,-tetrahydropyridin-3′- and -4′-yl)indoles—5-(α-Fluorovinyl)tryptamines

5-(α-Fluorovinyl)tryptamines 4a, 4b and 5-(α-fluorovinyl)-3-(N-methyl-1′,2′,5′,6′-tetrahydropyridin-3′- and -4′-yl) indoles 5a, 5b were synthesized using 5-(α-fluorovinyl)indole ( 7 ). The target compounds are bioisosteres of 5-carboxyamido substituted tryptamines and their tetrahydropyridyl analogs.     

Enantioselektive α-Alkylierung von Asparagin- und Glutaminsäure über die Dilithium-enolatocarboxylate von 2-[3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]essigsäure und 3-[3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]propionsäure

Overall Enantioselective α-Alkylation of Aspartic and Glutamic Acid through Dilithium Enolatocarboxylates of 2- [3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]acetic and 3-[3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]propionic Acid, respectively The pure methyl esters 10 of the heterocyclic carboxylic acids specified in the title were prepared in several steps by known methods from aspartic and glutamic acid, with overall yields of ca. 20%. The corresponding heterocyclic acids 11 were doubly deprotonated by LiNEt₂/BuLi or LiN(i-Pr)₂/BuLi to give enolatocarboxylates ( 3 ). The latter were reacted with electrophiles (MeOD, Mel, C₆H₅CH₂Br) to give the crystalline products 14 – 21 diastereoselectively. Hydrolysis of the imidazolidinone ring of three such products gave the corresponding α-branched aspartic and glutamic acids 22 – 24 of known absolute configuration, thus establishing the stereochemical course of the overall enantioselective alkylations.