Heteroadamantanes and their derivatives. 7. Synthesis and mass-spectrometric study of functional derivatives of 5-mono- and 5,7-disubstituted 1,3-diazaadamantanes

The chemical behavior of the carbonyl group of 5-mono and 5,7-disubstituted 6-oxo-1,3-diazaadamantanes was studied. The structures of the functional derivatives obtained were confirmed by IR and ¹H and ¹³C NMR spectral data. The behavior of the compounds under the influence of electron impact was studied, and the principal pathways of fragmentation of their molecules were ascertained.See [1] for Communication 6.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 647–653, May, 1989.     

Benzoid-quinoid tautomerism of Schiff bases and their structural analogs: LV. Crown-containing N-phenylimines derived from ortho-hydroxycarbaldehydes of the coumarin series

Schiff bases were synthesized from 3-hydroxy-6-oxo-6H-benzo[c]chromene-4-carbaldehyde, 5-hydroxy-4,7-dimethyl-2-oxo-2H-chromene-6-carbaldehyde, 6,7-dihydroxy-4-methyl-2-oxo-2H-chromene-8-carbaldehyde, 5,7-dihydroxy-4-methyl-2-oxo-2H-chromene-6,8-dicarbaldehyde, and 5-hydroxy-4,7-dimethyl-2-oxo-2H-chromene-6,8-dicarbaldehyde and (¹⁵N)aniline or aminobenzo-15-crown-5 (2,3,5,6,8,9,11,12-octahydrobenzo[b][1,4,7,10,13]pentaoxacyclopentadecin-15-amine), and tautomeric equilibrium between the hydroxy enimino and keto enamino forms of the 4- and 8-iminomethyl derivatives in solution was revealed by 1H NMR and electronic spectroscopy. Addition of alkaline earth cations to their solutions in acetonitrile displaced the tautomeric equilibrium toward the hydroxy enimino structure due to complex formation with the crown ether fragment.     

Heteroadamantanes and their derivatives. 6. Synthesis and mass-spectrometric investigation of 5-mono- and 5,6-disubtituted 6-oxo-1,3-diazaadamantanes

The corresponding 5-mono- and 5,7-disubstituted 6-oxo-1,3-diazaadamantanes were obtained with high yields by the condensation of mono- and ,'-disubstituted acetones with hexamethylenetetramine in the presence of glacial acetic acid, and their structures were confirmed by IR and PMR spectra. The behavior of the compounds under electron impact was studied, and the main fragmentation paths of their molecules were determined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1679–1685, December, 1985.     

Synthesis and conversions of polyhedral compounds. 28. Synthesis of 2-(naphthyl-1′) and 2-(2′-hydroxynaphthyl-1′) derivatives of 5,7-dialkyl-1,3-diazaadamantanes

2-Naphthyl and 2-(2′-hydroxynaphthyl) derivatives of 5,7-dialkyl-1,3-diazaadamantanes were synthesized by the reaction of the corresponding 5,7-dialkyl-3,7-diazabicyclo[3.3.1]nonanes with naphthaldehyde or 2-hydroxynaphthaldehyde. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, 1548–1555, October, 2007.     

Synthesis, Structure, and Alkylation of N-Methylmorpholinium 5-[2-Cyanoethyl-1-(4-hydroxy-3-methoxyphenyl)-2-thiocarbamoyl]-2,2-dimethyl-6-oxo-1,3-dioxa-4-cyclohexen-4-olate

N-Methylmorpholinium 5-[2-cyanoethyl-1-(4-hydroxy-3-methoxyphenyl)-2-thiocarbamoyl]-2,2-dimethyl-6-oxo-1,3-dioxa-4-cyclohexen-4-olate was obtained from the reaction of 4-hydroxy-3-methoxybenzaldehyde with cyanothioacetamide and Meldrum's acid in the presence of N-methylmorpholine. The molecular and crystal structure of the title compound have been established and its alkylation has been studied.     

Synthesis of Some New Thiazoles and Pyrazolo[1,5-a]pyrimidines Containing an Antipyrine Moiety

Ethyl 2-{2-[4-(2,3-dimethyl-5-oxo-1-phenyl-3-(pyrazolin-4-yl)]-2-cyano-1-(phenylamino)vinylthio}-acetate, 2-[4-(2,3-dimethyl-5-oxo-1-phenyl-(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]2-(4-oxo-3-phenyl-(1,3-thiazoilidin-2-ylidene))ethanenitrile, 2-[4-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]-2-(4-methyl-3-phenyl(1,3-thiazolin-2-ylidene))ethanenitrile, 2-(5-acetyl-4-methyl-3-phenyl(1,3-thiazolin-2-ylidene))-2-[4-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]ethanenitrile, and ethyl 2-(cyano(4-(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)thiazol-2-yl)methylene)-2,3-dihydro-4-methyl-3-phenylthiazole-5-carboxylate were synthesized by treatment of 2-(4-(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)thiazol-2-yl)-3-mercapto-3-(phenylamino)-acrylonitrile with appropriate halo ketones or halo esters. Also, 4-{2-[5,7-dimethyl-2-(phenylamino)(7a-hydropyrazolo[1,5-a]pyrimidin-3-yl](1,-thiazol-4-yl)}-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one derivatives were synthesized via reaction of 4-{2-[5-amino-3-(phenylamino)pyrazolin-4-yl](1,3-thiazol-2-yl)}-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one with β-diketone or β-keto ester. All synthesized compound were established by elemental analysis, spectral data, and alternative synthesis whenever possible.     

Proton magnetic resonance spectra of substituted adamantane-2,4-diones. Determination of the C-6 and C-9 stereochemistry

The 220 MHz ¹H NMR spectra of 6-hydroxy-7-methyl-6-phenyladamantane-2,4-dione, 6-hydroxy-5,7-dimethyl-6-phenyladamantane-2,4-dione, and 6-hydroxy-7,9-dimethyl-6-phenyladamantane-2,4-dione have been determined and complete proton assignments carried out with the aid of multiple irradiation. The stereochemistry of the C-6 and C-9 chiral centres have been determined and some of the factors affecting the magnitude of the geminal, vicinal and W coupling constants are discussed.     

Heteroadamantanes and their derivatives. 9. Synthesis of 1,5-dinitro-3,7-diazabicyclo[3.3.1]nonane and derived 2,2-disubstituted 5,7-dinitro-1,3-diazaadamantanes

Heating 1,5-dinitro-3,7-di(tert-butyl)-3,7-diazabicyclo[3.3.1]-nonane with concentrated hydrobromic acid gives 1,5-dinitro-3,7-diazabicyclo[3.3.1]nonane. Cyclization of the latter with various aldehydes and ketones gave a series of 2,2-disubstituted 5,7-dinitro-1,3-diazaadamantanes. The behavior of the synthesized compounds under electron impact has been studied.For Communication 8 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 538–542, April, 1990.     

New,convenient synthesis of 2-alkyl- and 2-vinylpyrazolo[3,4-d]-pyrimidine derivatives

Treatment of 1,3-dimethyl-6-hydrazinouracil with the appropriate dimethylformamide dialkylacetal afforded the, corresponding 2-alkyl-5,7-dimethylpyrazolo[3,4-d]pyrimidine-4,6-(5H,7H)diones. The reaction of 1,3-dimethyl-6-(α-methylbenzylidenehydrazino)uracils with dimethylformamide dimethylacetal or triethyl orthoformate gave the corresponding 5,7-dimethyl-2-vinylpyrazolo[3,4-d]pyrimidine-4,6(5H,7H)diones, respectively. Similarly, treatment of 1,3-dimethyl-6-(α-methylbenzylidenehydrazino)uraeils with triethyl orthopropionate yielded the corresponding 5,7-dimethyl-3-ethyl-2-vinylpyrazolo[3,4-d]pyrimidine-4,6(5H,7H)diones.     

Reactions of 1,3-Dialkyl-5-amino-1,3-dihydro-2<Emphasis Type="Italic">H</Emphasis>-imidazo-[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-2-ones with acetylacetone and ethyl acetoacetate

1,3-Dialkyl-5-amino-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones reacted with acetylacetone to give the corresponding 4-(1,3-dialkyl-2-oxo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-5-ylamino)pent-3-en-2-ones which underwent intramolecular cyclization to 1,3-dialkyl-5,7-dimethyl-1,3-dihydro-2H-imidazo[4,5-b]-[1,8]naphthyridin-2-ones on heating in polyphosphoric acid or diphenyl ether. Analogous reaction of 1,3-dialkyl-5-amino-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones with ethyl acetoacetate led to the formation of ethyl 3-(1,3-dialkyl-2-oxo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-5-ylamino)but-2-enoates whose cyclization afforded 1,3-dialkyl-8-hydroxy-7-methyl-1,3-dihydro-2H-imidazo[5,4-b][1,8]naphthyridin-2-ones.     

Building libraries of skeletally diverse scaffolds from novel heterocyclic active methylene compound through multi-component reactions

Libraries of skeletally diverse potential bioactive polycyclic/spirocyclic heterocyclic compounds; 2-amino-7,9-dimethyl-5-oxo-4-aryl-4,5,6,7-tetrahydropyrano[2,3-d]pyrazolo[3,4-b]pyridine-3-carbonitrile, 2′-amino-7′,9′-dimethyl-2,5′-dioxo-6′,7′-dihydro-5′H-spiro[indoline-3,4′-pyrano[2,3-d]pyrazolo[3,4-b]pyridine]-3′-carbonitrile, and 5,5′-(arylmethylene)bis(4-hydroxy-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one) have been synthesized through a multi-component reaction using novel heterocyclic active methylene compound 4-hydroxy-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-6(7H)-one as one of the building blocks. This protocol can be considered to be an efficient and eco-friendly strategy for diversity oriented synthesis.     

Unexpected course of rearrangement of substituted S-(1(3H)-isobenzofuranone-3-yl)isothiuronium bromides

Three series of S-(1(3H)-isobenzofuranone-3-yl)isothiuronium bromides differing in substitution at the isothiuronium moiety (none, one or two methyl groups) and at the benzene ring were prepared and characterized. These salts were then treated with various bases (acetate, triethylamine, Na₂CO₃) to give either 1-hydroxy-3-oxo-1,3-dihydro-2H-isoindol-2-carbothioamides or the product of S to N isobenzofuranone-3-yl migration, i.e., 1,3-dimethyl-1-(3-oxo-1,3-dihydro-2-benzofuran-1-yl)thioureas. If ammonia was used in reaction with N,N′-dimethyl isothiuronium salts then 3-hydroxy-2,3-dihydro-1H-isoindol-1-ones were formed together with 1,3-dimethyl-1-(3-oxo-1,3-dihydro-2-benzofuran-1-yl)thioureas in parallel reaction with the yields increasing with ammonia concentration. The formation of isoindolones takes place in two steps with an aldehyde intermediate, which can be trapped with N,N-dimethylhydrazine.     

Investigations in the series of heterocycles. 55. Synthesis and some reactions of 2-aryl-4-halo-6-oxo-1,3-thiazines

The reaction of 2-aryl-4-hydroxy-6-oxo-1,3-thiazines with Vilsmeier's reagent results in the formation of a mixture of 2-aryl-6-oxo-4-chloro-1,3-thiazines and their 5-formyl analogs. Reactions involving the nucleophilic replacement of the halogen and nucleophilic addition to an aldehydic group have been studied. The intramolecular cyclization of the oxime and phenylhydrazone of 6-oxo-2-phenyl-5-formyl-4-chloro-1,3-thiazine gives new heteroaromatic systems, viz., isoxazolo-[4,5-d]-1,3-thiazine and pyrazolo]4,5-d]-1,3-thiazine, respectively.For report 54 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1328–1334, October, 1984.     

Molecular Diversity from the L-Proline-Catalyzed,Three-Component Reactions of 4-Hydroxycoumarin,Aldehyde, and 3-Aminopyrazole or 1,3-Dimethyl-6-aminouracil

The three-component reaction of 4-hydroxycoumarin, aldehyde, and aminopyrazole in the presence of a catalytic amount of L-proline in ethanol under reflux conditions provided the cyclized product (dihydrochromeno[4,3-b]pyrazolo[4,3-e]pyridine-6(7H)-one), whereas under similar reaction conditions, replacing aminopyrazole by 1,3-dimethyl-6-aminouracil provided the acyclic three-component product (6-amino-5-((4-hydroxy-2-oxo-2H-chromen-3-yl)methyl)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione). This method is metal free and atom economical, and avoids column chromatographic purification as all the products can be purified by recrystallization.     

A novel redox reaction between 8-Aza-5,7-dimethyl-2-trifluoromethylchromone and alkyl mercaptoacetates. Facile synthesis of CF3-containing 2-pyridone derivatives

8-Aza-5,7-dimethyl-2-trifluoromethylchromone reacts with alkyl mercaptoacetates in the presence of triethylamine to give pyrido derivatives of 2-oxa-7-thiabicyclo[3.2.1]octane, which undergo the reductive ring opening to alkyl 2-[[3-(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)-3-oxo-1-(trifluoromethyl)propyl]sulfanyl]acetates.The latter can be also obtained directly from 8-aza-5,7-dimethyl-2-trifluoromethylchromone and behave as the masked alpha,beta-unsaturated ketone, 4,6-dimethyl-3-(4,4,4-trifluorobut-2-enoyl)pyridin-2(1H)-one. This compound was independently synthesized from 3-acetyl-4,6-dimethyl-2-pyridone, and its synthetic potential was studied. A wide variety of 2-pyridone derivatives containing the CF(3) group have been prepared in good to moderate yields.     

巴戟天内生真菌Trichoderma spirale A725中两个新的聚酮类化合物(英文)

综合运用硅胶柱色谱、反相硅胶柱色谱、Sephadex LH-20凝胶柱色谱以及制备型高效液相色谱技术对药用植物巴戟天内生真菌Trichoderma spirale A725的次生代谢产物进行分离纯化,得到6个聚酮类化合物,采用多种现代波谱技术确定其结构,分别为:6-羟基-4-异丙基-1,8-二甲基螺环[4.5]癸-1,8-二烯-7-酮(1),2-羟基-2,5-二甲基-7-氧代-5,7-二氢-2H-呋喃[3,4-b]吡喃-4-羧酸(2), 3-乙基-4-羟基-6-甲基-二氢-吡喃-2-酮(3),苯乙内酯A (4), 3-羟基-5-(4-羟基苄基)二氢呋喃-2(3H)-酮(5), 4-乙酰-3-羟基-6-甲基吡喃-2-酮(6).其中化合物1和2为新化合物,化合物3为新天然产物.此外,利用四株肿瘤细胞株(Hep G-2、MCF-7、SF-268及A549)对化合物1~6细胞毒活性进行评估,结果表明化合物1~6对上述肿瘤细胞均无明显的细胞毒活性.     

Quantum chemical study of mechanisms of organic reactions: V. Addition of ethane-1,2-dithiol to 4-hydroxy-4-methylpent-2-ynenitrile

The mechanism of nucleophilic addition of ethane-1,2-dithiol to 4-hydroxy-4-methylpent-2-ynenitrile has been studied at the DFT B3LYP/6-311++G(d,p) level of theory. The base-catalyzed reaction involves nucleophilic attack by deprotonated ethane-1,2-dithiol on the ß-carbon atom of the nitrile with formation of intermediate Z-vinylic carbanion which undergoes intramolecular cyclization with closure of 1,3-dithiolane ring. Further transformation of 2-[2-(2-hydroxypropan-2-yl)-1,3-dithiolan-2-yl]acetonitrile to 6,6-dimethyl-7-oxo-1,4-dithiaspiro[4.4]nonan-8-imine has also been studied.     

Synthesis of 4,6-diaryl-1-benzyl-6-hydroxy-5,5-dimethyl-2-oxopiperidine-3-carbonitriles and their analogs via a modified Reformatsky reaction

Organozinc compounds obtained from 1-aryl-2-bromo-2-methylpropanone and zinc react with N-benzyl-3-aryl-2-cyanoacrylamides or N-[6-(2-cyano-1-oxo-3-phenylprop-2-enylamino)hexyl]-2-cyano-3-phenylacrylamide to give 4,6-diaryl-1-benzyl-6-hydroxy-5,5-dimethyl-2-oxopiperidine-3-carbonitriles or 1,6-bis(6-aryl-3-cyano-6-hydroxy-5,5-dimethyl-2-oxo-4-phenylpiperidyl)hexanes as a single isomer with trans-located piperidine hydrogen atoms.     

Four component tandem Knoevenagel–Michael strategy for the assembly of arylaldehydes,N,N'-dimethylbarbituric acid, 4-hydroxy-6-methyl-2H-pyran-2-one and morpholine into unsymmetrical scaffold with three different heterocyclic rings

A new type of four component tandem Knoevenagel–Michael reaction has been found consisting in the assembly of benzaldehydes, N,N'-dimethylbarbituric acid, 4-hydroxy-6-methyl-2H-pyran-2-one and morpholine in alcohols, other organic solvents or water at room temperature without catalyst or any other additives, which results in the selective formation of unsymmetrical scaffold with three different heterocyclic rings in 63–98% yields. The crystal structure of morpholinium 5-[(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)(4-nitrophenyl)methyl]-1,3-dimethyl-2,6-dioxo-1,2,3,4-tetrahydropyrimidin-6-olate has been confirmed by X-ray diffraction.     

Synthesis of fluorinated 2,6-heptanediones and 2-oxa-6- azabicyclo[2.2.2]octanes from 1,4-dihydropyridines

Electrophilic fluorination of Hantzsch-type 1,4-dihydropyridines with Selectfluor^® led to the formation of new fluorinated 2,6-heptanediones - dialkyl 2,4-diacetyl-2,4-difluoro-3-phenylpentanedioates. Novel 2,6-heptanedione derivatives in reaction with hydrazine hydrate easily form 6-amino-4,7-difluoro-3-hydroxy-1,3-dimethyl-5-oxo-8-phenyl-2-oxa-6-azabicyclo[2.2.2]octanes instead of the corresponding diazepine derivatives. The obtained 2-оxa-6-azabicyclo[2,2,2]octanes are thermally stable at the temperatures below 50°С. At higher temperatures rearrangement of 2-oxa-6-azabicyclo[2,2,2]octanes offers new fluorine-containing pyrazolinone derivatives - alkyl esters of 2-fluoro-2-((4-fluoro-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)(phenyl)methyl)-3-oxobutanoates.