Potential antidepressants: 2-(Phenylthio)aralkylamines

1989 ◽  
Vol 54 (7) ◽  
pp. 1995-2008 ◽  
Author(s):  
Jiří Jílek ◽  
Jiří Urban ◽  
Petr Taufmann ◽  
Jiří Holubek ◽  
Antonín Dlabač ◽  
...  
Keyword(s):  
Nmr Spectra ◽  
Benzyl Chloride ◽  
Lithium Aluminium Hydride ◽  
Pharmacological Profile ◽  
H Nmr ◽  
Lithium Aluminium ◽  
Alternative Approach ◽  
Phenyl Acetonitrile ◽  
Claisen Reaction ◽  
Pharmacological Testing

Reactions of 2-(phenylthio)benzyl chloride with dimethylamine, diethylamine, pyrrolidine, piperidine, morpholine, and 1-methylpiperazine afforded the title compounds VI-XI. Reaction of 2-(phenylthio)benzaldehyde with nitromethane gave the nitrostyrene XIV which was reduced with lithium aluminium hydride to 2-(2-(phenylthio)phenyl)ethylamine (XVI). This was transformed to the N-methyl and N,N-dimethyl derivatives XVIII and XIX. The Claisen reaction of (2-(phenylthio)phenyl)acetonitrile with ethyl acetate afforded compound XXI which was cleaved by phosphoric acid to (2-(phenylthio)phenyl)acetone (XX). The Leuckart-Wallach reaction afforded the formamide XXIII which was used as starting material for preparing the amines XXIV-XXVI. The alternative approach to these compounds starting by reaction of the aldehyde XII with nitroethane was complicated by the fact that in addition to the nitropropene XV 2-(phenylthio)benzonitrile was also formed. The synthetic use of the inhomogeneous XV resulted then in mixtures of amines XXIV-XXVI with IV-VI which was followed by means of mass and 1H NMR spectra. The amines XXIV-XXVI were oxidized to the sulfoxides XXVII-XXIX. The oily bases were transformed to crystalline salts and spectra of all homogeneous bases were recorded. Pharmacological testing showed the amine VI (VÚFB-15 370) to be a promising potential antidepressant. The amines XI and XXV showed also pharmacological profile of potential antidepressants.

Preparation of 12,20-disubstituted lupane derivatives

1979 ◽  
Vol 44 (1) ◽  
pp. 194-210 ◽  
Author(s):  
Vladimír Pouzar ◽  
Alois Vystrčil
Keyword(s):  
Hydroxy Group ◽  
Sodium Borohydride ◽  
Nmr Spectra ◽  
Unsaturated Ketone ◽  
Lithium Aluminium Hydride ◽  
H Nmr ◽  
Unsaturated Alcohols ◽  
Lithium Aluminium ◽  
Primary Hydroxy Group ◽  
Derivatives Of

Ketoester I was reduced to diol VI. The higher reactivity of its primary hydroxy group was made use of for the preparation of 12α-hydroxy derivatives VII, VIII and X the oxidation of which led to oxo derivatives XII, XIII and XIV. The reduction of the 12-oxo group in compounds XII and XIV with lithium aluminium hydride takes place stereospecifically under formation of 12α-hydroxy derivatives VII and X, while on reduction with sodium in 1-propanol corresponding 12β-hydroxy derivatives XV and XVI are also formed. Reduction of the unsaturated ketone XVII with sodium borohydride gave unsaturated alcohols XVIII and XX. As acetoxy ketone XXIV was obtained from olefin XIX in a 12% yield only, its alternative preparation was carried out from acetoxy ketone XXXIV via the intermediates XXXII, XXXV, XXVIII and XXXI in an overall yield of 27%. The structures of the derivatives of 12-lupene (III, V, XVII, XIX and XXI), 12-lupanol (II, VII, X, XV, XXXI and XXVII) and 12-lupanone (I, XII, XIII, XIV, XXIII, XXIV, XXXIII and XXXIV) were confirmed by the analysis of their 1H NMR spectra.

Atropodiastereoisomerism and pseudoassymetry with axial chirality of ligands in bis(2-methyl-1-naphthyl)methanols

1979 ◽  
Vol 44 (10) ◽  
pp. 2946-2969 ◽  
Author(s):  
Otakar Červinka ◽  
Karel Bláha ◽  
Anna Fábryová ◽  
R. Fink ◽  
Dick Van der Helm ◽  
...  
Keyword(s):  
Nmr Spectra ◽  
Lithium Aluminium Hydride ◽  
X Ray Diffraction ◽  
X Ray ◽  
Axial Chirality ◽  
H Nmr ◽  
Lithium Aluminium

On reduction of bis(2-methyl-1-naphthyl) ketone (I) with lithium aluminium hydride alcohol VI was formed which isomerized into alcohol VII. Both alcohols, the configuration of which were proved using 1H-NMR spectra and X-ray diffraction, represent the first example of compounds having a centrum of pseudoassymetry and axial chirality of ligands.

Reaction of 3,4a-disubstituted 4,4-dimethyl-5,6β-epoxy-A-homo-5β-cholestane derivatives with reducing agents

1985 ◽  
Vol 50 (11) ◽  
pp. 2457-2470 ◽  
Author(s):  
Helena Velgová ◽  
Jaroslav Zajíček
Keyword(s):  
Sodium Borohydride ◽  
Reducing Agents ◽  
Epoxide Ring ◽  
Lithium Aluminium Hydride ◽  
H Nmr ◽  
Lithium Aluminium ◽  
Nmr Data ◽  
Epoxy Alcohols

Reaction of all stereoisomeric 3-acetoxy-4,4-dimethyl-5,6β-epoxy-A-homo-5β-cholestan-4a-ols I-IV with lithium aluminium hydride and reduction of 3-acetoxy-4,4-dimethyl-5,6β-epoxy-A-homo-5β-cholestan-4a-ones XXII and XXIII with sodium borohydride were studied. It was found that reductive opening of the 5β,6β-epoxide ring occured only in the case of the derivatives III and IV due to 5(O)n participation of the 3α-oxygen-containing substituent under formation of the transannular 3α,5α-epoxides VIII and IX, resp. On reduction of the 4a-keto epoxides XXII and XXIII with sodium borohydride the trans-epoxy alcohols III and I were formed. On the basis of 1H NMR data the conformation of the A-ring in the epoxides I-IV, XXII, and XXIII is also discussed.

Preparation of secondary alcohols of high optical purity

1986 ◽  
Vol 51 (2) ◽  
pp. 401-403 ◽  
Author(s):  
Otakar Červinka ◽  
Anna Fábryová ◽  
Irina Sablukova
Keyword(s):  
Nmr Spectroscopy ◽  
Optical Purity ◽  
Optically Active ◽  
Secondary Alcohols ◽  
Lithium Aluminium Hydride ◽  
Enantioselective Reduction ◽  
H Nmr ◽  
Lithium Aluminium ◽  
High Optical Purity ◽  
Optically Pure

Partially resolved enantiomers of optically active alcohols I-V, obtained by enantioselective reduction of the corresponding ketones with lithium aluminium hydride in the presence of (-)-quinine, were converted into crystalline 3,5-dinitrobenzoates or phenylcarbamates. The esters of the nearly optically pure enantiomers were separated by crystallization from the generally more soluble esters of the racemates. Optical purity of the hydrolytically liberated alcohols was determined by 1H NMR spectroscopy in the presence of chiral shifting agents.

Potential antidepressants: 1-(2-(Methoxy- and hydroxyphenylthio)phenyl)-2-propylamines

1990 ◽  
Vol 55 (4) ◽  
pp. 1077-1098 ◽  
Author(s):  
Jiří Urban ◽  
Zdeněk Šedivý ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Miroslav Ryska ◽  
...  
Keyword(s):  
Ethyl Formate ◽  
Secondary Amines ◽  
Primary Amines ◽  
Alternative Route ◽  
Lithium Aluminium Hydride ◽  
Tertiary Amines ◽  
Lithium Aluminium ◽  
Boron Tribromide ◽  
Pharmacological Testing ◽  
By Products

2-(Methoxyphenylthio)benzaldehydes Xa-Xd were reacted with nitroethane in boiling acetic acid to give the corresponding 1-aryl-2-nitropropenes XIIa-XIId; benzonitriles XIIIa and XIIIc and benzaldoximes XXIc and XXId were isolated as by-products. Chromatographed compounds XIIa-XIId were reduced with lithium aluminium hydride to the primary amines VIIa-VIId, and formylated by heating with ethyl formate to the formamides XIVa, XIVc, and XIVd. Reduction of the formamides with lithium aluminium hydride afforded the secondary amines VIIIa, VIIIc, and VIIId, and methylation of the primary amines with formic acid and formaldehyde gave the tertiary amines IXa, IXc, and IXd. Compound VIIIa was prepared also by an alternative route starting from the nitrile XIIIa and proceeding via XIXa and XIVa. Some of the methoxylated amines were demethylated either by heating with pyridine hydrochloride or by treatment with boron tribromide to the title compounds IVa, IVc, Vc, Vd, VIa, and VIc. The amines prepared were transformed to salts for characterization and for pharmacological testing. Compound VIIIa (hydrogen oxalate V⁄FB-15 475) showed clearly the character of a potential antidepressant.

Bicyclo[2.2.2]octane-2-spirocyclohexanes, Part 2[1]. Reduction Products of Spirodiisophora-3′,6-dione

1991 ◽  
Vol 46 (11) ◽  
pp. 1557-1567 ◽  
Author(s):  
Frederick Kurzer ◽  
Zakir Kapadia
Keyword(s):  
Catalytic Hydrogenation ◽  
Nmr Spectra ◽  
Cyclohexane Ring ◽  
Lithium Aluminium Hydride ◽  
Lithium Aluminium ◽  
Functional Derivatives ◽  
The Individual ◽  
C Nmr

The reduction of spirodiisophora-3′,6-dione under various conditions occurs exclusively at its 3′-keto-function in the cyclohexane ring. The action of lithium aluminium hydride yields the 3′-eq-hydroxyketone, while catalytic hydrogenation, hydroboration and the action of metal borohydride produces the 3′-ax-epimer. The conformers give rise to pairs of distinct epimeric functional derivatives. Anhydrous hydrazine removes the 3′-oxygen function of the 3′,6-dione entirely, with formation of spirodiisophor-6-one. Catalytic hydrogenation of the 3′-oximino-6-ketone yields the corresponding 3′-amine. The 13C NMR spectra of the individual products are assigned and correlated with their structures.

Bicyclo[2.2.2]octane-2-spirocyclohexanes, Part 3. Synthesis and Reactions of Mono- and Dibromospirodiisophoranes

1992 ◽  
Vol 47 (1) ◽  
pp. 126-138 ◽  
Author(s):  
Frederick Kurzer ◽  
Zakir Kapadia
Keyword(s):  
Nmr Spectra ◽  
Ring System ◽  
Lithium Aluminium Hydride ◽  
Ring Contraction ◽  
Lithium Aluminium ◽  
The Individual ◽  
C Nmr

Halogenation by the appropriate amounts of bromine or N-bromosuccinimide converts spirodiisophora-3',6-dione successively into the 4'-ax-mono- and 2',4'-diax-dibromo-3',6-dione. The latter is reduced by lithium aluminium hydride to the corresponding 6,3'-ketol. with retention of one or both bromo-substituents, depending on conditions. The bromoketones undergo the Favorski ring-contraction under the influence of alkalis to compounds of the bicyclo[2.2.2]octane-2-spirocyclopentane ring-system . The 13C NMR spectra of the individual products are assigned and correlated with their structures.

The internal rotational potential in benzyl chloride

1986 ◽  
Vol 64 (7) ◽  
pp. 1322-1325
Author(s):  
Ted Schaefer ◽  
Rudy Sebastian ◽  
Glenn H. Penner
Keyword(s):  
Internal Rotation ◽  
Long Range ◽  
Nmr Spectra ◽  
Benzyl Chloride ◽  
Polar Solvent ◽  
Low Energy ◽  
Coupling Constants ◽  
Molecular Orbital Theory ◽  
Orbital Theory ◽  
H Nmr

The 1H nmr spectra of benzyl chloride in dilute CS2 and acetone-d6 solutions are analyzed. The long-range coupling constants are consistent only with a low-energy conformation in which the C—Cl bond lies in a plane perpendicular to the benzene plane. Geometry optimized computations at the STO 3G level of molecular orbital theory agree with this conclusion and yield a nearly pure twofold barrier to internal rotation of 8.6 kJ/mol. In CS2 solution the long-range couplings yield 8.8 kJ/mol, rising to 11.2 kJ/mol in acetone solution. This increase in the internal barrier in a polar solvent is similar to that found for benzyl fluoride, but in the latter the barrier itself is very much smaller than in benzyl chloride.

1-(4-Cyclopentylphenyl)piperazine and its 4-substituted derivatives; Synthesis and biological screening

1987 ◽  
Vol 52 (7) ◽  
pp. 1834-1840 ◽  
Author(s):  
Zdeněk Vejdělek ◽  
Miroslav Protiva
Keyword(s):  
Antimicrobial Activity ◽  
Benzyl Chloride ◽  
Addition Reaction ◽  
Anthelmintic Activity ◽  
Ethyl Formate ◽  
Lithium Aluminium Hydride ◽  
Biological Screening ◽  
Acyl Chlorides ◽  
Lithium Aluminium

Heating the hydrochlorides of 4-cyclopentylaniline and diethanolamine to 250 °C gave 1-(4-cyclopentylphenyl)piperazine (I). Acylation of I with ethyl formate and the corresponding acyl chlorides gave the amides II, VI, and VII which were reduced with lithium aluminium hydride to the piperazines III, VIII, and IX. Treatment of I with benzyl chloride and with 4-chloro-1-(4-fluorophenyl)butan-1-one under different conditions led to compounds IX and XI. Addition reaction of I to 1,2-epoxybutane resulted in the amino alcohol V. The products showed marginal tranquillizing activity (especially compound VIII), some antimicrobial activity in vitro and some anthelmintic activity.

Potential antidepressants: 10-Amino-2-chloro-10,11-dihydrodibenzo[b,f]thiepins

1989 ◽  
Vol 54 (7) ◽  
pp. 1979-1994 ◽  
Author(s):  
Vladimír Valenta ◽  
Marie Vlková ◽  
Jiří Holubek ◽  
Jiřina Metyšová ◽  
Miroslav Protiva
Keyword(s):  
Formic Acid ◽  
Secondary Amines ◽  
Lithium Aluminium Hydride ◽  
Pharmacological Profile ◽  
Substitution Reactions ◽  
Lithium Aluminium ◽  
Primary And Secondary Amines ◽  
Aqueous Formaldehyde

Reduction of N-(2-chloro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)formamide with lithium aluminium hydride resulted in the methylamino compound IV. The dimethylamino compound V was obtained by methylation of 10-amino-2-chloro-10,11-dihydrodibenzo[b,f]thiepin with formic acid and aqueous formaldehyde. Substitution reactions of 2,10-dichloro-10,11-dihydrodibenzo[b,f]thiepin with a series of primary and secondary amines afforded the title compounds VI to XXVIII. The bases were transformed to salts and pharmacologically tested. Only the pyrrolidino compound IX (hydrogen succinate VÚFB-15 551) showed a clear pharmacological profile of a potential antidepressant.

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