Investigation of the stereochemistry of N-substituted 2,5-dimethyl-4-piperidinones by NMR spectroscopy

The conformations of the cis and trans isomers of N-substituted 2,5-dimethyl-4-piperidinones were studied by means of the¹H and¹³C NMR parameters. It was established that in the case of bulky and electron-acceptor substituents attached to the N atom the cis isomers are virtually completely represented by the chair (2a,5e) conformation, while the trans isomers are characterized by the chair (2e,5e) twistboat (2a,5e) chair (2a,5a) conformational equilibrium. It is demonstrated that 1-tert-butyltrans-2,5-dimethyl-4-piperidinone hydrochloride has the twist (2a,5e) conformation.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, pp. 1760–1768, August, 1990.     

Effects of N substituents on structure in 2-N-substituted 8-oxyquinolines: Conjugation between the unshared electron pair on the nitrogen atom and the aromatic ring

All-Union Reagents and Especial-Purity Substances Research Institute. Translated from Zhurnal Strukturnoi Khimii, Vol. 30, No 2, pp. 152–177, March–April, 1989.     

Mass spectroscopic study of 2,5-dimethyl-4-benzoyl- and 2,5-dimethyl-4-benzylpyridine derivatives

The dissociative ionization of sixteen 4-benzoyl- and 4-benzylpyridine derivatives and their deuteroanalogs has been studied. An ortho effect, due to the benzoyl and benzyl radicals in the methyl group in the 5-position of the pyridine ring, has been detected. It has also been established that fragmentation of 4-benzoylpyridines substituted with a nitro group in the benzene ring leads to [M-OH]⁺ ions, due to the ortho effect, whereas fragmentation of 4-benzylpyridines leads to [M-C₆H₅R]⁺ ions. The probability of a given process depends on the position and nature of any substituent in the benzene ring; this makes it possible to identify different isomers in a given series of compounds.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 810–816, June, 1987.     

Stereochemistry of nitrogen heterocycles. 68. Stereochemistry of 2,5-dimethyl-4-piperidone, 2,5-dimethyl-4-piperidol,and their N-benzoyl derivatives

The isomers of 1-benzoyl-2,5-dimethyl-4-piperidone were obtained and equilibrated (89.8% cis 10.2% trans isomer, preferred conformations 2a, 5e, and 2a, 5a). The position of the equilibrium between the isomers of 2,5-dimethyl-4-piperidone was determined by two independent methods (89.5% trans 10.5% cis isomer). The differences in the free energies of the isomers, the conformational energy of the -CH₃ group, and the energy of syn-axial 1,3-interaction between the CH and the unshared electron pair were calculated; the decrease in the conformational energy of the -methyl group in the series of piperidine (1.6), 4-piperidone (1.47), and N-acyl-4-piperidone (1.28 kcal/mole) was explained by the successive weakening of the repulsive interaction between the -CH₃ group and the n-pair of the nitrogen as a result of the flattening of the ring and of the conjugation between the free electron pair of the nitrogen and the electrons of the acyl carbonyl group. The last previously unknown fourth isomer of 2,5-dimethyl-4-piperidol, which exists in the 2e,4a,5a conformation, was obtained by the reduction of cis-1-benzoyl-2,5-dimethyl-4-piperidone followed by debenzoylation. In contrast to the secondary amine, its N-benzoyl- and N-benzyl-substituted derivatives exist in the alternative 2a,4e,5e conformation. The configurations and conformations of the isomers were determined by means of the IR and NMR spectra.For Communication 67, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 953–961, July, 1989.     

Arylation of 2,5-dimethyl-4-phenylpyridine

The position of the pyridine ring is arylated by reaction of 2,5-dimethyl-4-phenylpyridine with phenyllithium and p-tolyllithium. Destructive oxidation of the diaryl-substituted pyridines primarily affects the pyridine ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1359–1361, October, 1970.     

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.     

PMR studies of N-substituted-2,5-dimethyl-4-piperidones

PMR characteristics of some isomeric 1-substituted-2,5-dimethyl-4-piperidones are reported and major isomers shown to have a trans 2,5-dimethyl configuration. Differences between benzylic methylene signals of isomeric 1-benzyl analogs provide evidence of the preferred conformation of the cis derivative. Evidence of the D/H exchange of α-protons in 1,2,5-trimethyl-4-piperidone base and of addition of D₂O to the carbonyl group of the corresponding hydrochloride and methiodide salts is also demonstrated. The effect of a 2-methyl substituent upon the chemical shifts of N-methyl groups in some piperidine methiodides is discussed.     

Synthesis of 2,5-dimethyl- and 1,2,5-trimethyl-4-dimethoxyphosphinylpiperid-4-ols

Dimethyl phosphite is condensed with 2,5-dimethyl- and 1,2,5-trimethylpiperid-4-ones in the presence of alkali metal alkoxides. It is shown that 2,5-dimethyl- and 1,2,5-trimethyl-4-dimethoxyphosphinyl-piperid-4-ols are formed in both cases in the same stereoisomeric forms and in high yields. Methylation of the piperidol isomer which was not substituted at the nitrogen atom indicated that the two piperidols formed had the same configuration.     

Mass spectrometric investigation of stereosomeric 1,2-dimethyl-4-substituted decahydroquinol-4-ol N-oxides. Concerning the configuration of the asymmetric nitrogen atom

The main fragmentation pathways of the N-1, C-2 and C-4 stereoisomers of the 1,2-dimethyl-4-R-transdecahydroquinoline-4-ol N-oxides (R=C?CH, CH?CH₂ and C₂H₅) under electron impact are discussed. The correlation between the mass spectrometric chromatographic behaviour and the configuration of polar groups in the N-oxides examined is discussed. The mass spectra of the N-1 stereoisomers may be subdivided into two groups, depending only on the orientation of N→O group and not of the 4-OH group. The spectra of N-oxides with the axial N-oxide group reveal less intense ions and much more intense [M? CH₃]⁺, [M? O]⁺, [M? OH]⁺ and ions, whereas in the spectra of their equatorial epimers the abundance of the ions exceeds the intensities of the latter ions.     

Reductive N-alkylation of 2,5-dimethyl-4-triphenylsilylpyridine over metal sulfides

Conclusions The Re₂S₇ catalyst was proposed, and optimum conditions were established, for the selective hydrogénation of the pyridine ring in 2,5-dimethyl-4-triphenylsilylpyridine and its subsequent N-ethylation with ethanol, without involving the phenyl radicals attached to silicon. The Pt and Pd sulfides are less active under analogous conditions.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, pp. 1901–1902, August, 1973.     

Benzylation of 2,5-dimethyl-4-phenyl(p-alkylbenzyl) pyridines

New substituted 4-phenyl-2-benzyl- and 2,4-dibenzylpyridines were obtained, and some of their transformations were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 91–94, January, 1972.     

2,6-Di-tert-butylphenylvinyl ether: Effect of the unshared oxygen electron pair on the13C-13C spin-spin interaction constant

Conclusions The proximity of sp²-hybridized unshared pair of oxygen atoms result in a secondary, positive contribution in the constant of spin-spin interaction between neighboring carbon nuclei in the aromatic ring.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 82–85, January, 1987.We would like to thank V. D. Ryabov for kindly supplying the sample of 2,6-di-tert-butylphenol.     

Structures involving unshared electron pair. The Crystal Structures of As(OCOCH3)3 and As2O(OCOCH3)4

As₂O(OCOCH₃)₄, reported now for the first time, was obtained, besides As(OCOCH₃)₃ by dissolving As₂O₃ in acetic anhydride. The crystals of As(OCOCH₃)₃ (A) (monoclinic, space group Cc, Z = 4, a = 9.970(2), b = 13.203(2), c = 8.272(1) Å, β = 117.01(2)°) and of As₂O(OCOCH₃)₄ (B) (monoclinic, space group P2₁/n, Z = 4, a = 13.966(5), b = 8.127(4), c = 12.706(4) Å, β = 95.14(1)°) are built up from discrete molecules defined by chemical formulae As(OCOCH₃)₃ and (CH₃OCO)₂As? O? As(OCOCH₃)₂, respectively. The molecular structure of both compounds is based on the AsO₃ pyramid: in (A) with the As? O bonds of 1.841(6) Å and the O? As? O angle of 89.9(3)° as a mean, in (B) with slightly different values and with the As? O? As angle of 127.7(4)° at the bridging oxygen atom. The additional weak chelating contacts are at the distances As…O from 2.625(9) to 2.745(10) Å in (A) and from 2.72(1) to 2.84(2) in (B). The actual arsenic coordination can be described as very distorted octahedral in (A) and square-pyramidal in (B).     

Synthesis of 4-substituted 1-methyl(benzyl)-2,5-dimethyl-4-R-aminopiperidines

Schiff base derivatives of 1-methyl(benzyl)-2,5-dimethylpiperidin-4-ones with phenyl, -pyridyl, benzyl, and -hydroxyethyl substituents attached to the imine nitrogen atom react with organometallic compounds to give analogously substituted piperidine bases with methyl, allyl, phenyl, and benzyl substituents in the 4-position. Pure individual geometric isomers of these newly synthesized compounds have been isolated and their structures determined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 954–958, July, 1987.     

Synthesis of benzoates of 1,4-bis(2,5-dimethyl-4-hydroxypiperidino)-2-butene and 1,4-bis-(2,5-dimethyl-4-hydroxypiperidino)-2-butyne

1,4-Bis(2,5-dimethyl-4-hydroxypiperidino)-2-butene and 1,4-bis(2,5-dimethyl-4-hydroxypiperidino)-2-butyne (II and III) were obtained by the action of 1,4-dibromo-2-butene and 1,4-dibromo-2-butyne on the form of 2,5-dimethyl-4-piperidol (I). The benzoates (IV and V) were obtained by acylation of II and III with benzoyl chloride.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 352–353, March, 1971.     

Quantum-chemical characteristics of the unshared pair of electrons in molecules of pyridine and its derivatives

Theoretical and Experimental Chemistry -     

Analysis of the long-range effect of the nitrogen unshared pair on the direct13C-1H coupling constants in the vinyl group of N-vinylazoles

Conclusions A long-range effect of the nitrogen unshared pair on the direct¹³C-¹H coupling constants is seen in the case of approximation of the corresponding proton and heteroatom to a distance on the order of their Van der Waals radii. The magnitude of this effect decreases with increasing averaged ionization potential of the nitrogen unshared electron pair.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 872–876, April, 1988.