Cyanoethylation of some n-substituted 2,5-dimethyl-4-piperidones

1,2,5-Trimetnyl- and 1-(-chlorocrotyl)-2,5-dimethyl-5-(-cyanoethyl)-4-piperidones were synthesized and separated into individual isomers. The corresponding isomeric 5-(-carboxyethyl)-4-piperidones were obtained by hydrolysis. The isomeric 1,2,5-trimethyl-3,5-bis(-cyanoethyl)- and 1,2,5-trimethyl-3,3,5-tris(-cyanoethyl)-4-piperidones were synthesized by subsequent cyanoethylation of the individual 1,2,5-trimethyl-5-(-cyanoethyl)-4-piperidone isomers.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 479–481, April, 1971.     

Synthesis and configuration of diastereomeric 1-(β-dimethylaminoethyl)-2,5-dimethyl-4-plperidols

Diastereomeric 1-(-dimethylaminoethyl)-2,5-dimethyl-4-piperidols were synthesized and their configurations were studied. The spatial orientation of the substituents in the , , and isomers of 2,5-dimethyl-4-piperidol was established, and the stereochemistry of the reduction of 2,5-dimethyl-4-piperidone with sodium in alcohol, with lithium aluminum hydride, and by catalysis on Raney nickel was studied by PMR spectroscopy. A series of transformations at the nitrogen atom of the piperidine ring do not change the configuration of 2,5-dimethyl-4-piperidols, but the stereochemistry of the reduction of the keto group in 2,5-dimethyl-4-piperidones with lithium aluminum hydride depends markedly on the character of the substituent attached to the piperidine nitrogen.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1374–1378, October, 1973.     

Highly enantioselective synthesis of 3,3-disubstituted 4-piperidones by michael alkylation of chiral piperidone imines

A method for the highly enantioselective synthesis of (3S)- and (3R)-3,3-disubstituted 4-piperidones with an optical purity of 98% based on the deracemizing alkylation of 3-substituted 4-piperidones during Michael addition of their chiral imines to electrophilic alkenes was developed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1072–1078, August, 1992.     

Indole derivatives

The Fischer cyclization of arylhydrazones of 1,3-dimethyl-, 1, 3, 5-trimethyl-, and 1, 3, 6-trimethyl-4-piperidones is examined. An unusual duration of the reaction is found, resulting in rearrangement products (1, 2, 3, 4-tetrahydropyrimido[3,4-a]indoles). It is shown that hydrogenation of the latter gives 2-(-dimethylaminoalkyl)-3-methylindoles.For Part XXX, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1219–1224, September, 1970.     

Asymmetric synthesis and absolute configuration of 1-α-phenylethyl-2,5-dimethyl-4-piperidone isomers

Reaction of the methyl iodide of trans-1,2,5-trimethyl-4-piperidone with S--phenylethylamine proceeds asymmetrically and leads in 66% optical yield to the formation of the cis- and trans-diastereomeric pair of 1-(-phenylethyl)-2,5-dimethyl-4-piperidone, in which the new asymmetric centers possess the 2S,5S- and 2S,5R-configurations, respectively. According to x-ray structural analysis, the minor trans-1-(-phenylethyl)-2,5-dimethyl-4-piperidone component possesses the 2R,5S-configuration. The occurrence of asymmetric synthesis accompanying transamination was confirmed via the preparation of enantiomers of trans-2,5- and trans-1,2,5-trimethyl-4-piperidones.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1641–1648, December, 1986.     

Effect of the character of the substitution on the reversible cyclization of 1-alkenyl 2-alkylaminoethyl ketones into 4-piperidones

Summary In aqueous solutions 4-piperidones form labile systems consisting of a cyclic and an open-chain form. In the case of 4-piperidones having a bulky alkyl on the nitrogen and a substituent on C₂ or a medium-sized alkyl on the nitrogen and two 2-substituents (hindered piperidones) equilibrium is displaced toward the open-chain form.The spectrographic part of the investigation was carried out by T. M. Fadeeva, to whom the authors express their thanks.     

Absolute configurations of optically active trans-4-ketoperhydroquinoline and its cis- and trans-N-phenylethyl derivatives

The reduction of optically active N-(-phenylethyl)-4-keto-^9,10-octahydroquinoline with lithium aluminum hydride gives a mixture of cis and trans isomers of N-(-phenylethyl)-4-ketoperhydroquinoline. Only one optically active acetate and the free trans-4-ketoper-hydroquinoline base were isolated in the hydrogenolysis of each of the isomers. The absolute configurations and conformations of the two-ring -piperidones obtained were established by optical rotatory dispersion, circular dichroism, and an examination of three-dimensional models.Communication XXXII from the series Stereochemical Investigations; see [1] for communication XXXI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1656–1663. December, 1972.     

New method of synthesis of 3-alkyl-4-piperidones

A new method is presented for the synthesis of 3-substituted 4-piperidones by alkylation of lithium derivatives of 4-(-phenylethylimino) piperidines using alkyl halides.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 372–374, March, 1986.     

Crystal and Molecular Structure of 1-( p -Tolyl)-4-[4-(N-naphthalimido)butyl]piperazine

An X-ray structure analysis of 1-(p-tolyl)-4-[4-(N-naphthalimido)butyl]piperazine (I) was carried out: a=9.551(3), b=13.775(3), á=8.917(4) , =103.96(3), =101.47(4), =92.60(3)°, V=1110.4(7) ³, Z=2,_calc=1.279 g/cm³, =0.644 mm, space group P 1, 4239 nonzero reflections, R=0.056. The molecule is linear elongated. The p-tolyl and naphthalimide fragments are almost planar, while the piperazine cycle has a chair conformation. The long well-packed molecules form parallel and antiparallel chains with van der Waals interactions between them.     

First asymmetric synthesis of 4-piperidones. Preparation of optically active diastereomers of 1-α-phenylethyl-2-methyl-4-piperidone

The fundamental possibility of carrying out the asymmetric synthesis of 4-piperidones on the basis of the transamination of 1-substituted 2-methyl-4-piperidone methiodides by optically active -phenylethylamine was demonstrated; the optical yield of the asymmetric transamination is 50%. The occurrence of asymmetric synthesis was confirmed by the isolation of enantiomers of 2-methyl-4-piperidol by reduction of the individual diastereomers of 1--phenyl-ethyl-2-methyl-4-piperidone to the corresponding 4-piperidols with subsequent removal of the chiral substituent attached to the nitrogen atom.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1378–1382, October, 1985.     

Synthesis of isomeric 3-phenyl-5-(pyridylmethylene)-2-thiohydantoins and their S-methylated derivatives. Molecular and crystal structures of (5Z)-3-phenyl-5-(pyridin-2-ylmethylene)-2-thiohydantoin and (5Z)-2-methylthio-3-phenyl-5-(pyridin-2-ylmethylene)-3,5-dihydro-4H-imidazol-4-one

Three procedures were used for the synthesis of -, , and -pyridyl-substituted (5Z)-3-phenyl-5-(pyridylmethylene)-2-thiohydantoins: the reaction of 2-thiohydantoin with the corresponding aldehyde in AcOH in the presence of AcONa, the two-step one-pot synthesis with the use of the same starting compounds, and three-component condensation of aryl isothiocyanate, glycine, and aldehyde in AcOH. Alkylation of the resulting thiohydantoins with iodomethane in the presence of a base afforded the corresponding S-methylated derivatives, viz., 2-methylthio-3-phenyl-5-(pyridylmethylene)-3,5-dihydro-4H-imidazol-4-ones. The structures of (5Z)-3-phenyl-5-(pyridin-2-ylmethylene)-2-thioxoimidazolin-4-one and (5Z)-2-methylthio-3-phenyl-5-(pyridin-2-ylmethylene)-3,5-dihydro-4H-imidazol-4-one were established by X-ray diffraction analysis.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2734–2739, December, 2004.     

Some reactions of 2-chloro-3-(β-chloroethyl)-4,6-dihydroxypyridine

The chemical properties of 2-chloro-3-(-chloroethyl)-4,6-dihydroxypyridine (I) have been studied. It has been shown that this compound, which is relatively stable in acids and in neutral and, particularly, in alkaline media, readily splits off hydrogen chloride under mild conditions and is converted into derivatives of 2, 3-dihydro-5-azabenzofuran. The dehalogenation of I in an acid medium yielded 3-(-chloroethyl)-4, 6-dihydroxypyridine, which was converted into 4, 6-dichloro-3-(-chloroethyl)pyridine and into 6-chloro-4-methoxy-3-vinylpyridine.     

Acetylene derivatives

Summary The conditions were found for the hydration of 4-alken-2-ynylamines, and by this means several previously inaccessible -amino ketones were synthesized in high yield; such amino ketones are of interest for the synthesis of 4-piperidones and of some physiologically active compounds, in particular anesthetics.     

Rearrangement of the carbon chain of the para-substituent of 4-(α-methoxy -β-bromoethyl)-2,6-di-tert-butylphenol by the action of sodium methoxide

Conclusions Rearrangement of the carbon chain of the para-substituent to form 4-hydroxy-3,5-di-tert-butylphenyl-acetaldehyde dimethylacetal occurs during the reaction of 4-(-methoxy--bromoethyl)-2,6-di-tert-butyl-phenol with sodium methoxide.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 626–629, March, 1972.     

1-Methyl(benzyl)-2,5-dimethyl-4-N-[aryl(alkyl)amino]piperidines and their acyl derivatives

N-Substituted -aminopiperidines and their benz- and propioamides have been synthesized from -piperidones. The stereoisomeric amines and amides have been separated and identified.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 949–953, July, 1987.     

2-Amino-4-[2-(5-nitro-furyl)vinyl]thiazole and its derivatives

The reactions of 4-bromo-1-(5-nitro-2-furyl)but-1-en-3-one and its 2-methyl and 2-chloro derivatives with thiourea and its N-allyl and N-phenyl derivatives have yielded 2-amino-4-[-5-nitro-2-furyl)-vinyl]thiazole and its - and N-substituted derivatives. 2-Amino-4-[-(5-nitro-2-furyl)vinyl]thiazole and its -methyl derivative have also been prepared by the direct reaction of the corresponding , -unsaturated ketones with bromine and an excess of thiourea in chloroform, as was shown by a comparison of UV spectra. A series of N-acyl derivatives of the aminothiazoles has been obtained. UV and IR spectra are given.     

Synthesis,molecular structure,and absolute configuration of 1-α-pheitylethyl-3-(2-cyanoethyl)-4-piperidone

The Michael addition of acrylonitrile to the pyrrolidine enamine of 1-(S--phenyl-ethyl)-4-piperidone proceeds with the formation of. a 1:1 mixture of l-(S--phenyl ethyl)-3-(2-cyanoethyl)-4-piperidone diastereomers. A diastereomer isolated in pure form was shown by x-ray diffraction structural analysis to have S-configuration of the new chiral center at C₍₃₎ of the piperidone ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp, 1656–1662, December, 1985.     

First Asymmetric Total Synthesis of (R,E)-1-[4-(3-Hydroxyprop-1-enyl)phenoxyl]-3-methylbutane-2,3-diol

A new anti-inflammatory active phenylpropenoid, (R,E)-1-[4-(3-hydroxyprop-1-enyl) phenoxyl]-3-methylbutane-2,3-diol (1), isolated from the stem wood of Zanthoxylum integrifoliolum, has been synthesized for the first time using commercially available 4-hydroxy benzaldehyde (2). The key step involves the Sharpless asymmetric dihydroxylation of olefin (3).

Protolysis of some α-amino-β-(1-pyrimidyl)propionic acids and their analogs

The protolysis constants of -(1-uracilyl)propionitriles and -(1-uracilyl)propionic -amino--(1-pyrimidyl)propionic, and -amino--(1-pyrimidyl)butyric acids (willardiine analogs) were determined. The electronic effect of substituents and of transannular interaction of the groups on the deprotonation constants is discussed. -(1-Uracilyl)--alanine (willardiine) was isolated by Gmelin from the seeds of Acacia willardiana.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 708–712, May, 1972.