Lactam acetals

The cis-trans isomerization in a number of enamines — 1-methyl-2-(2'-R-2'-R'-methylene)pyrrolidines,-piperidines, and -hexahydroazepines — depends substantially on the nature of the 2'-substituent and the ring size. The energy barrier to this process decreases as the ability of the substituents to delocalize the anionic center in the transition state increases. The free energy of activation of rotation about the C=C bond is appreciably lower for six-membered enamines than for the corresponding seven- and five-membered analogs.     

Lactam acetals

The dependence of pK _a (in nitromethane) and _I of methylene-group-substituted 1-methyl-2-methylenepiperidines is expressed by the equation pK _a =–0.41+11.8 _I. The basicities of tertiary enamines are more than five orders of magnitude greater than the basicities of the corresponding secondary enamines.See [1] for communication VII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 385–388, March, 1974.     

Lactam acetals

Derivatives of pyrrolo-, pyrido-, and azepino[2,3-b]quinolones were synthesized by condensation of N-methylbutyro-, N-methylvalero-, and N-methylcaprolactam diethyl acetals with ethyl anthranilate. The corresponding ethoxy derivatives were obtained by reaction of these compounds with triethyloxonium tetrafluoroborate, and condensed 4-chloroquinolines were synthesized with POCl₃.See [1] for communication IX.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 670–674, May, 1974.     

Lactam acetals

A number of 1-methyl-2-(2′-substituted methylene)pyrrolidines were synthesized, and their ionization constants in nitromethane were measured. The ΔpK values obtained were compared with the corresponding values for their six- and seven-membered analogs. The increased basicity of enamines with six-membered rings is apparently due to the strain that develops in the cations of the five- and seven-membered enamines during the formation of an endocyclic C=N⁺ bond.     

Lactam acetals

The alkylation of O- and N-methyl derivatives of butyrolactam, valerolactam, and caprolactam with dimethyl sulfate has been performed and the synthesis of the corresponding lactam acetals has been effected. It has been shown that the rate of alkylation depends fundamentally on the size of the ring of the initial compound.For Communication VI, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1532–1535, November, 1973.     

Lactam acetals

It is shown in the case of the reaction of N-methylbutyro-, N-methylvalero-, and N-methylcaprolactam diethylacetals with benzyl cyanide that the five-membered acetal is the most reactive in the reaction with compounds having an active methylene link. 1-Methyl-3-(Ωphenyl-Ω-benzoxymethylene)-2-pyrrolidone is primarily formed in the reaction of N-methyl-2-pyrrolidone diethylacetal with C₆H₅COCl. The reaction of N-methylcaprolactam diethylacetal with acrylonitrile gives a mixture of N-methylcaprolactam, 1-methyl-2-ethoxy-3-(Β-cyanoethyl)-4, 5,6,7-tetrahydroazepine, and 2-methyl-1,9-dehydro-9-cyano-2-azabicyclo-[5.2.0] nonane.     

Lactam acetals

The rate of deuteration of 1-methyl-2-aryliminolactams depends on the electronic character of the substituent in the benzene ring and on the size of the lactam ring. Deuterium exchange proceeds at the highest rate in piperidine derivatives that have electron-donor substituents in the benzene ring.     

Lactam and acid amide acetals. 63. Reaction of amide acetals with enaminodicarbonyl compounds

Corresponding dienediaminodicarbonyl compounds were synthesized by the reactions of a series of dimethylaminomethylenedicarbonyl compounds with N,N-dimethylacetamide and N-methylcaprolactam diethylacetals. In the reaction of N-methylvalerolactam diethylacetal, the process is accompanied by a rearrangement with the formation of a 3-methylenepiperidon-2-one derivative. It was found that the introduction of a substituted amino group into the meso-position of the intermediate -alkoxyenamine (in the preparation of dienediaminodicarbonyl compounds) takes place intermolecularly, and a general scheme of the unusual reaction studied has been proposed.For communication 62, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 218–223, February, 1991.     

Lactam and amide acetals. 56. Synthesis of pyrimidines from N-carbamoylamidines

N-Carbamoyl-N,N-dimethylformamidine reacts with ethyl anthranilate to give quinazoline-2,4-dione, and with cyanoacetamide to give 4-amino-5-carbamoylpyrimidin-2-one. The reaction of dimethylacetamide diethyl acetal with urea proceeds via N-carbamoyl-N,N-dimethylacetamidine with the subsequent formation of 4-dimethylamino-6-methyl-pyrimidin-2-one and 4,6-dimethyl-sym-triazin-2-oneFor Communication 55, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 81–84, January, 1990.     

Lactam acetals and acid amides. 32. Lactim-lactam tautomerization of condensed 4-pyridones

The tautomeric properties of a number of condensed 4-pyridone derivatives were investigated. The existence of lactim-lactam tautomerization in this series of compounds was established by IR and UV spectroscopy. It is shown that when α substituents are present in the 4-pyridone molecule, both intramolecular electronic effects and the effect of substituents on solvation of one or another tautomeric form and, consequently, on the position of the equilibrium should be taken into account. See [1] for communication 31. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 349–353, March, 1980.     

Lactam and acid amide acetals. 58. New synthesis of 3-nitro-5-hydroxybenzofurans

Previously unknown 3-nitro-5-hydroxybenzofuran derivatives were obtained by condensation of p-benzoquinones with nitro enamines.See [1] for Communication 57.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 597–600, May, 1990.     

Lactam and acid amide acetals. 71. New synthesis of 3-nitro-6-hydroxyindole derivatives

Previously unknown 3-nitro-6-hydroxyindole derivatives were synthesized by condensation of p-benzoquinone with secondary -nitro enamines.See [1] for Communication 70.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 40–45, January, 1992.     

Lactam acetals and acid amides. 31. Synthesis,protonation, and basicities of some heterocyclic enamino ketones

The protonation of cyclic enamino ketones of the pyrrolidine, piperidine, and hexahydroazepine series, as well as their noncyclic analogs, was studied by PMR spectroscopy. It is shown that the presence of a CH₂ or CH₃ group in the “enamine” position leads to C protonation (in CF₃COOH). In the case of enamino ketones that do not contain substituents in the “enamine” α position N-and O-protonated forms are observed in CF₃COOH. The measured pK_a values (in 10% alcohol) and the ΔpK_a values (in nitromethane) of the enamino ketones show that the compounds for which C protonation is characteristic are two to three orders of magnitude more basic than in the case of compounds that do not contain substituents in the “enamine” α position; this is explained by the different character of protonation. See [1] for communication 30. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 344–348, March, 1980     

Lactam and acid amide acetals 68. 1-Cyanomethyl-2-pyrrolidone diethylacetal in the synthesis of 7,8-trimethylenepurine derivatives

1-Cyanomethyl-2-cyaniminopyrrolidine was synthesized by the reaction of 1-cyanomethyl-2-pyrrolidone diethylacetal with cyanamide. The product undergoes Thorpe—Ziegler cyclization under the influence of sodium ethoxide to give 2-amino-3-cyano-5,6-dihydro-7H-pyrrolo[1,2-a]imidazole, from which 4-amino derivatives of pyrrolo[2,1-f]purine were synthesized.See [1] for Communication 67.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 754–758, June, 1991.     

Lactam and amide acetals. 69. Synthesis and properties of 3-(aminomethylene)-2-indolinone derivatives

Oxindole derivatives reacted with the diethyl acetals of dimethylformamide and dimethylacetamide to give the corresponding derivatives of 3-(aminomethylene)-, (aminoethylidene)-, and (ethoxyethylidene)-2-indolinone. These products were then easily converted to N-aryl- and N-alkylaminomethyleneoxindoles upon treatment with aryl or alkyl amines. The alkylation of N,N-dimethylaminomethylene-2-indolinones by dimethyl sulfate and triethyloxonium tetrafluoroborate, and the reactions of the resulting methyl sulfates and tetrafluoroborates with nucleophilic reagents were studied. The configuration of the 3-(aminomethylene)-2-indolinone derivatives prepared at the enamine C=C double bond was investigated by NMR. The free energies of activation for the cis—trans isomerization were determined in a number of cases.For Communication 68, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1190–1198, September, 1991.     

Lactam and amide acetals. 52. Reaction of dimethylformamide diethylacetal with 2,2-dimethyl-4,6-dioxo-1,3-dioxane (Meldrum's acid)

Depending on the conditions of carrying out the reaction of dimethylformamide diethylacetal with the Meldrum's acid, either 2,2-dimethyl-4,6-dioxo-5-(N,N-dimethyl-aminomethylene)-1,3-dioxane or N,N,N¹N¹-tetramethylformamidinium salt of 2,2-dimethyl-4,6-dioxo-5-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)methylene-1,3-di-oxane are formed. The two compounds can react with primary amines to form N-substituted 2,2-dimethyl-4.,6-dioxo-5-aminomethylene-1,3-dioxanes.For Communication 51, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 184–187, February, 1988.     

Lactam analogues of galiellalactone

A synthetic route to lactam analogues of the fungal STAT3 inhibitor galiellalactone is presented. The synthesis involves a one-pot tosylamide amide coupling/intramolecular Michael addition and an introduction of an α,β-unsaturation, regioselectively directed by the tosyl functionality. An iodolactonization of the octahydroindolizine 9 and a re-opening of the lactone were employed for introducing an iodo substituent, facilitating the preparation of 8-substituted analogues (e.g., 4) using a Suzuki cross-coupling.     

Lactam and acid amide acetals 57. Synthesis,protonation, and acid-base properties of condensed derivatives of 4-oxo-1,4-dihydro-1,8-naphthyridine

A number of 4-oxo-1,4-dihydro-1,8-naphthyridine derivatives that differ with respect to the sizes of the azaand carbocycles were synthesized by the reaction of 3-amino-4-ethoxycarbonyl-5,6-dihydro-7H-pyrindine and 3-amino-4-ethoxycarbonyl-5,6,7,8-tetrahydroisoquinoline with N,N-dimethylacetamide diethylacetal and N-methylbutyrolactam, N-methylvalerolactam, and N-methylcaprolactam diethylacetals and subsequent cyclization of the intermediate amidines. It was established by UV and ¹H and ¹³C NMR spectroscopy that the protonation of these compounds takes place at the exocyclic oxygen atom. The dependence of the ionization constants of the compounds obtained in 70% DMFA on the size of the saturated cyclic fragments of the molecules was established.See [1] for Communication 56.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 643–651, May, 1990.     

Lactam and acid amide acetals 65. Study of the reaction of DMF diethylacetal with 5-carbamoyl(thiocarbamoyl)-6-aminopyrrolizine derivatives

The reaction of DMF diethylacetal with 5-carbamoyl(thiocarbamoyl)-6-aminopyrrolizine derivatives proceeds regioselectively at the amido (thioamido) group without involving the 5-amino group. The synthesized acyl(thioacyl)amidines are starting compounds in the production of pyrimido[5,4-e]pyrrolizine derivatives.See [1] for Communication 64.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 349–354, March, 1991.     

A New Lactam from Cannabis sativa

Chemistry of Natural Compounds - A new lactam, 5-hydroxy-1-[(4-hydroxyphenyl)methyl]-2-pyrrolidinone (1), was isolated from the ethyl acetate extract of Cannabis sativa L. The structure was...