Hydroamination of 2,2'-methylenebiscyclohexanone with aniline and formic acid

10-Phenyl-sym-octahydroacridinium salts and stereoisomeric 10-phenylperhydroacridines were obtained by the action of aniline and formic acid on 2,2'-methylenebiscyclohexanone.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 376–377, March, 1971.     

SYNTHESIS OF SOME DITHIOCARBAMATE DERIVATIVES AND THEIR ANTIMICROBIAL ACTIVITY

Some new, 2-[(N-substituted aminothiocarbonylthio)acetyl]aminothiazole, N-substituted aminothiocarbonylthioacetylaminodiphenylmethane and 9-[(N-substituted aminothiocarbonylthio)acetyl]aminofluorene derivatives were synthesized by reacting 2-(chloroacetyl) aminothiazole, chloroacetylaminodiphenylmethane, and 9-(chloroacetyl)aminofluorene with secondary amine dithiocarbamate derivatives in acetone respectively. The structure elucidation of the compounds was performed by IR, ¹H-NMR, and FAB⁺-MS spectral data. The substances were tested for their antimicrobial activity.     

Studies on organophosphorus compounds 101. A facile synthetic route to trifluoromethylated aminophosphonic acids and phosphonopeptides

A series of dialkyl 1-(N-substituted amino)-2,2,2-trifluoroethylphosphonates was synthesized by Arbuzov-type reactions involving an N-substituted trifluoromethylimidoyl chloride and the appropriate trialkyl phosphite. The resulting C=N bond was successfully hydrogenated by NaBH₄CN treatment. The subsequent deprotection of the amino group was conducted either by hydrogenolysis with Pd black or by use of cerium ammonium nitrate, depending on the structure of the substituent on the amino function. The free amino group thus obtained underwent a coupling reaction with an aminoacyl chloride in the usual manner. © 1998 John Wiley & Sons, Inc. Heteroatom Chem 9:139–146, 1998     

Reaction of organozine reagents derived from dialkyl 2,2-dibromomalonates and methyl 4,4-dibromo-3-oxoalkanoates with 2-oxochromene-3-carboxamides

Organozinc compounds obtained by treatment of dialkyl 2,2-dibromomalonates with zinc reacted with N-substituted 2-oxochromene-3-carboxamides to give dialkyl 1a-R-carbamoyl-2-oxo-1a,7b-dihydro-2H-cyclopropa[c]chromene-1,1-dicarboxylates or alkyl 2-R-1,3,4-trioxo-2,3-dihydro-1H,9bH-chromeno[3′,4′:1,3]-cyclopropa[1,2-c]pyrrole-9c-carboxylates. Reactions of N-substituted 2-oxochromene-3-carboxamides with zinc enolates derived from methyl 4,4-dibromo-3-oxoalkanoates led to the formation of the corresponding 9c-alkyl-2-R-2,3-dihydrochromeno[3′,4′:1,3]cyclopropa[1,2-c]pyrrole-1,3,4-triones.     

Heteroatomic derivatives of aziridine. 13. New macroheterocyclic compounds containing arylalkyl and functional groups attached to the endocyclic nitrogen atoms

The reaction of N-substituted aziridines with 1,2-ethanedithiol and 1,2-bis(mercap tomethyl)-4,5-dimethylbenzene leads to N-substituted diamines. The reaction of the latter with adipic and phthalic acid dichlorides gives N-substituted macroheterocycles.See [I] for Communication 12.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1228–1230, September, 1981.     

Acylation and bromination of some 2-mercaptothieno[2,3-d]pyrimidinones and synthesis of their 2-amino derivatives

The acylation of 2-thio-3-R-4-oxo-3,4-dihydrothieno[2,3-d]-pyrimidines by means of benzoyl chloride was studied. Depending on the reaction conditions, it may take place with the formation of S-substituted and N-substituted derivatives. The bromination of the sodium salts of thienopyrimidines and their S- and N-substituted derivatives is accompanied by the formation of disulfides, which do not react with electrophilic reagents but react with amines to give 2-amino derivatives of thienopyrimidines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1333–1336, October, 1985.     

Cyclopropanation of N-substituted 3-aryl-2-cyanoprop-2-enamides and derivatives of 5,5-Dimethyl-2-oxo-2,5-dihydrofuran-3-carboxylic acid and 2-oxochromene-3-carboxylic acid with bromine-containing zinc enolates

Zinc enolates derived from 1-aryl-2,2-dibromoalkanones react with N-substituted 3-aryl-2-cyanoprop-2-enamides and 5,5-dimethyl-2-oxo-2,5-dihydrofuran-3-carboxylic and 2-oxochromene-3-carboxylic acid derivatives to give, respectively, N-substituted 2-alkyl-3-aryl-2-aroyl-1-cyanocyclopropane-1-carboxamides, 6-(4-bromobenzoyl)-4,4,6-trimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylic acid ethyl ester and morpholide, and 1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropla[c]chromene-1a-carboxylic acids as a single geometric isomer. Treatment of 1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxylic acids with carboxylic acid anhydrides leads to the formation of the corresponding 9c-alkyl-1-aryl-3,4-dioxo-9b,9c-dihydro-2,5-dioxacyclopenta[2,3]cyclopropa[1,2-a]naphthalen-1-yl carboxylates.     

Preparation and root growth-inhibitory activity of N-substituted 2-(2-chloroacetamido)-3-(furan-2-yl)propanamides

A series of N-substituted 2-(2-chloroacetamido)-3-(furan-2-yl)propanamides (16--18) was prepared through the reaction of chloroacetyl chloride with N-substituted 2-amino-3-(furan-2-yl)propanamides (15), which were obtained via condensation of 2-(tert-butoxycarbonylamido)-3-(furan-2-yl)propanoic acid (Boc-furylalanine) (8) with amines (9, 11, 13), followed by hydrolysis of the resultant N-substituted Boc-furylalanine acid amides (10, 12, 14) in the presence of HCl/dioxane. The biological activity of the prepared 16, 17 and 18 as root growth inhibitors was examined by germination assay using rape seed. At the concentration of 5.0 x10 (-5) M, the most active compound, 2-(2-chloroacetamido)-N-(2,6-diethylphenyl)-3-(furan-2-yl)propanamide (16 n), showed potent root growth-inhibitory activity of 76% towards rape seedlings.     

Peculiarities of formation of decahydroacridine-1,8-diones on the basis of 1,3-dioxocyclohexane compounds in various media

The conditions for the formation of N-substituted decahydroacridine-1,8-diones from -R-methylenebiscyclohexane-1,3-diones and 5,5-dimethyl-3-(N-methylamino)-2-cyclohexen-1-one in ethanol, isopropanol, and DMSO have been studied. Methods have been developed for preparation of 1,8-dioxo-10-methyldecahydroacridines which contain furyl and 5-nitrofuryl substituents at the 9 position.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 475–481, April, 2000.     

Synthesis of alkylated aminofluorenes by palladium-catalyzed substitution at halofluorenes

New N-substituted 2-amino-9,9-dialkylfluorenes optionally bearing electron-withdrawing substituents such as nitro or cyano in position 7 can be synthesized starting from 2-halo-9,9-dialkylfluorenes by Pd-catalyzed substitution with amines. Chiral amino groups can be introduced by this method too. 2-N,N-Dimethylamino-7-nitro-9H-fluorene was obtained in a convenient way by reductive amination. The N-substituted 2-amino-7-nitro-9H-fluorenes are promising candidates for fluorescence probes for femtosecond solvation dynamics.     

Synthesis of N′-substituted 4-amino piperidines with a shielded nitrogen atom

A method was developed for the synthesis of N-substituted 2,2,6,6-tetramethyl- and 1,2,-2.6,6-pentamethyl-4-aminopiperidines starting from triacetoneamine cyanohydrin through the corresponding aminonitriles with subsequent reductive decyanation. The peculiarities of salt formation from N-substituted 4-aminopiperidines with a shielded nitrogen atom are examined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1672–1678, December, 1971.     

Synthesis and cyclization of N-(9-alkylcarbazol-3-yl)-β-alanines

The reaction of 3-amino-9-alkylcarbazoles with acrylic and itaconic acids yields N-substituted amino acids, which were converted into derivatives of 4-carboxy-2-pyrrolidinone and dihydropyrimidinedione.Kaunas Technological University 3028 Kaunas, LithuaniaTranslated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1637–1640, November–December, 1999.     

Synthesis of 1-Acyl-5-amino-4-ethoxycarbonylpyrazoles from Monohydrazides of Cyclohexenedicarboxylic Acids and Ethyl Ethoxymethylenecyanoacetate

Heating monohydrazides of cyclohexenedicarboxylic acids with ethyl ethoxymethylenecyanoacetate at reflux gives the corresponding N-substituted hydrazides. This reaction carried out in pyridine gives 1-acyl-5-amino-4-ethoxycarbonylpyrazoles. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1332–1335, September, 2005.     

Five-membered 2,3-dioxo heterocycles: C. Reaction of methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carbocylates with acyclic enamines

Methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carbocylates react with N-substituted ethyl 3-amino-3-phenylprop-2-enoates, ethyl 3-aminobut-2-enoates, 3-amino-1,3-diphenylprop-2-en-1-ones, and dimethyl 2-arylaminofumarates to give 9-ethoxycarbonyl-, 9-benzoyl-, and 8,9-bis(methoxycarbonyl)-4-cinnamoyl-1,7-diazaspiro[4.4]nona-3,8-dienes.     

Synthesis and Intramolecular Cyclization of N-Substituted 2-Amino-4-aryl-4-oxo-2-butenoic Acids

Treating 4-aryl-2,4-dioxobutanoic acids with aromatic amines, 4-aminoantipyrine, and benzophenone hydrazone furnished N-substituted 2-amino-4-aryl-4-oxo-2-butenoic acids that existed in solutions in enaminoketone and iminoketone forms. The acids obtained underwent in the presence of acetic anhydride cyclization into N-substituted 5-aryl-3-imino-3H-furan-2-ones.     

A Novel Synthesis of 1-Aryl-9-alkyl-2, 3, 3a, 4, 9, 9a-hexahydro-1H-pyrrolo[2, 3-b] quinoxalines by lithium aluminium hydride reduction of N-phenyl-1-benzimidazolyl-succinimides

The N-substituted 1-benzimidazolyl-succinimides 6a – v (Scheme 1, Table 1 and 2) have been prepared by the reaction of benzimidazole and its derivatives with maleimides. Reduction of the N-cyclohexyl and N-cyclo-octyl substituted 1-benzimidazolyl-succinimides 6i – k with lithium aluminium hydride gives the normally expected substituted (N-alkyl-3-pyrrolidinyl)benzimidazoles 14i – k . However by LiAlH₄-reduction of the N-phenyl substituted 1-benzimidazolylsuccinimides 6a – h mainly the 1-aryl-9-alkyl-2, 3, 3a, 4, 9, 9a-hexahydro-1H-pyrrolo[2, 3-b]quinoxalines 7a – h are obtained. The mechanism of this unusual reduction has been elucidated.     

Reaction of methyl thiocarbamate with nonsubstituted malonyl dichloride. Effect of conditions on reaction direction

The reaction of methyl thiocarbamate with malonyl dichloride at low temperatures provides an N-substituted thiocarbamate, whereas prolonged boiling in high-boiling solvents gives rise to 4-hydroxy-2-(methylsulfanyl)-6H-1,3-oxazin-6-one that was also prepared by treatment of the N-substituted thiocarbamate with malonyl chloride in toluene and chlorobenzene.     

Syntheses of 3-substituted 2,3-dihydrobenzofuranes, 1,2-dihydronaphtho(2,1-b)furanes,and 2,3-dihydro-1H-indoles by tandem ring closure-S(RN)1 reactions

3-Substituted 2,3-dihydrobenzofuranes (7a-c), 1,2-dihydronaphtho(2,1-b)furanes (10a-c), and N-substituted 2,3-dihydro-1H-indoles (8a-c, 9a,b) are obtained in very good yields by S(RN)1 photostimulated reactions in liquid ammonia from adequate haloaromatic compounds ortho-substituted with a suitable double bond (3a,b; 4a,b; 5a; 6a,b) and Me3Sn-, Ph2P-, and -CH2NO2 anions. The novelty of the work involves the versatile application of a 5-exo ring closure process during the propagation cycle of the S(RN)1 reaction; the alkyl radical intermediates formed react with the nucleophiles to afford the ring closure-substituted heterocycles. The factors governing the observed product distribution are discussed.     

Characterization and Inhibitor Screening of Plateau Zokor Lactate Dehydrogenase C4

Lactate dehydrogenase C4 (LDH-C4) is considered to be a target protein for the development of contraceptives. In this work, the characterization of plateau zokor LDH-C4 and the screening of a series of N-substituted oxamic acids as inhibitors against zokor LDH-C4 were reported. The cDNA of zokor LDH-C gene was cloned and expressed in Escherichia coli, from which the protein was purified and further characterized. The protein was a tetramer (LDH-C4) and thermally stable up to 62 °C with a K _m of 63.9 μM for pyruvate and with optimal pH values of 7.95 and 10.1 for the forward and backward reactions respectively. Virtual and in vitro screening against zokor LDH-C4 revealed eight N-substituted oxamic acids with IC50s ranging from 198 to 2513 μM, higher than that of oxamic acid (150 μM) and (ethylamino)(oxo)acetic acid (59 μM). The inhibition potencies of N-substituted oxamic acids tested are in the micromolar range, and the increase in the length of substituting chain seems not to increase inhibition potency.     

One-Pot Synthesis of N-Substituted 4-Aryl-1,4-dihydropyridines Under Solvent-Free Conditions and Microwave Irradiation

 The three-component condensation of benzaldehyde derivatives, alkyl propiolates, and primary amines catalyzed by silica gel, zeolite HY, montmorillonite K-10, and acidic alumina under microwave irradiation gave N-substituted 4-aryl-1,4-dihydropyridines in short reaction times and high yields. The best results were obtained with silica gel.