Three-component condensation of 3-aminothiophene-2-carboxylic acid derivatives with aldehydes and Meldrum’s acid

A convenient method was developed for the synthesis of the previously unknown substituted 6,7-dihydro-4H-thieno[3,2-b]pyridin-5-ones based on the three-component condensation of 3-aminothiophenes, Meldrum’s acid, and aromatic aldehydes. 3-Aminothiophenes are easily formed in situ by decarboxylation of 3-aminothiophene-2-carboxylic acids in an acidic medium. Sodium salts of the latter acids were prepared by alkaline hydrolysis of the corresponding available esters.     

Three-component condensation of 2-aminothiophene-3-carboxylic acid derivatives with aldehydes and Meldrum’s acid

New approach to the synthesis of 4,7-dihydro-5H-thieno[2,3-b]pyridin-6-ones using 2-aminothiophenes unsubstituted at position 3 of the thiophene ring has been developed. Labile 2-aminothiophenes have been obtained by the in situ decarboxylation of unstable 2-amino-3-thiophenecarboxylic acids. The three-component condensation of 2-aminothiophenes with aromatic aldehydes and the Meldrum’s acid is the key step of the process.     

Three-component condensation of 5-aminoimidazole derivatives with aldehydes and Meldrum’s acid. Synthesis of 3,4,6,7-tetrahydroimidazo[4,5-b]pyridin-5-ones

A convenient method for the synthesis of the earlier unknown substituted 3,4,6,7-tetrahydroimidazo[4,5-b]pyridin-5-ones was developed based on a three-component condensation of 5-aminoimidazole derivatives, aldehydes, and Meldrum’s acid. Unstable aminoimidazole derivatives were readily formed in situ by decarboxylation of 5-amino-4-imidazolecarboxylic acids in acidic medium at room temperature, whose sodium salts were obtained by the alkaline hydrolysis of the corresponding, readily available esters.     

One-Pot Synthesis of Thieno[2,3-b]pyridine and Pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine Derivatives

Russian Journal of Organic Chemistry - 2-Acyl-4,5,6-trialkyl-3-aminothieno[2,3-b]pyridines,...     

Three-component condensation of 5-aminopyrazole derivatives with isatins and Meldrum’s acid. Synthesis of 1,7-dihydrospiro[pyrazolo[3,4-b]-pyridine-4,3′-indole]-2′,6(1′H,5H)-diones

A new method for the synthesis of hitherto unknown substituted 1,7-dihydrospiro-[pyrazolo[3,4-b]pyridine-4,3′-indole]-2′,6(1′H,5H)-diones based on three-component condensation of 5-aminopyrazoles with Meldrum’s acid and isatins is developed.     

Synthesis of derivatives of pyrido[3′,2′:4,5]furo[3,2-c]isoquinoline heterocyclic system

An approach to the synthesis of derivatives of new heterocyclic system, pyrido[3′,2′:4,5]-furo[3,2-c]isoquinoline, was suggested. A condensation reaction of substituted 3-cyanopyridin-2(1H)-ones with methyl 2-(chloromethyl)benzoate and subsequent treatment of the condensation product with potassium tert-butoxide leads to substituted pyrido[3′,2′:4,5]furo[3,2-c]-isoquinolin-5(6H)-ones. Similarly, a condensation reaction of substituted 3-cyanopyridin-2(1H)-ones with 2-(chloromethyl)benzonitrile and subsequent treatment of the condensation product with potassium tert-butoxide gives substituted 5-aminopyrido[3′,2′:4,5]furo[3,2-c]-isoquinolines.     

Synthesis of new pyridazino[4′,3′:4,5]-thieno[3,2-d]-1,2,3-triazine and pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine derivatives

Summary 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-one (2), 3-substituted 8,9-diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-ones (3a–c), 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-one (4), 8-chloro-3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazine (5), 8-substituted 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazines (6a–h) and 7-substituted 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-ones(7a–c) were synthesized from 5-amino-3,4-diphenylthieno[2,3-c]pyridazine-6-carboxamide (1).

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Synthese neuer Pyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-und Pyrimido[4,5:4,5]thieno[2,3-c]pyridazin-Derivate

Zusammenfassung Folgende Verbindungen wurden ausgehend von 5-Amino-3,4-diphenylthieno[2,3-c]pyridazin-6-carboxamid (1) synthetisiert: 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-on (2), 3-substituierte 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-one (3a–c), 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8[7H]-on (4), 8-Chlor-3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin (5), 8-substituierte 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazine (6a–h) und 7-substituierte 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-one (7a–c).

     

An expeditious access of 2,5′-dioxo-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carboxylate by reaction of isatin,ethyl cyanoacetate and enaminone in water

We have demonstrated three component reaction of isatin, enaminone and ethyl cyanoacetate leading to sprirooxindole scaffold without catalyst in water. The synthetic protocol has several advantages like wide substrate scope, atom-economy and operationally simple experimental procedures which provides rapid access to library of compounds. The mechanistic details of the reaction has been investigated during the course of study.     

Alkylation of pyrimido[5′,4′:5,6]pyrido[3,2-b]indol-4-one derivatives

Alkylation of 11-benzyl-3,11-dihydro-4H-pyrimido[5′,4′:5,6]pyrido[3,2-b]indol-4-one with methyl iodide and methyl bromoacetate in DMF gave 3-alkylpyrimidopyridoindolones as the corresponding salts. The reaction in acetone in the presence of K₂CO₃ yielded 3,6-disubstitution products. Alkylation with DMF dimethyl acetal gave a mixture of the 3- and 6-alkylpyrimidopyridoindol-4-one bases. The structure of 4-oxo-4,6-dihydro-3H-pyrimido-[5′,4′:5,6]pyrido[3,2-b]indol-11-ium chloride (3b) was proved by X-ray diffraction analysis.     

Thieno[2,3-b]pyridine-2-carbohydrazide in Polyheterocyclic Synthesis: The Synthesis of Pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine,Pyrido[3′,2′:4,5]thieno[3,2-d][1,2,3]triazine,and Pyrazolyl,Oxadiazolylthieno[2,3-b]pyridine Derivatives

Pyrdine-2(1H)-thione 1 reacted with ethyl chloroacetate 2 to give 2-S-ethoxy-carbonylmethylpyridine derivative 3, which could be cyclized into thieno[2,3-b]-pyridine-2-carbohydrazide derivative 5 by boiling with hydrazine hydrate. The latter compound reacted with cinnamonitrile derivatives 6a, b, triethylorthoformate, formic acid, dimethylformamide-dimethylacetal, and diethyl carbonate to give the corresponding shiff base 7a, b and pyrido[3′,2′;-4,5]thieno[3,2-d]pyrimidine derivatives 10–13 in respective manner. On the other hand, compound 5 also reacted with carbondisulphide and phenyl isothiocyanate to afford the corresponding 2-(1,3,4-oxadiazolo-2-yl)thieno[2,3-b]pyridine derivatives 18 and 22. Finally, compound 5 reacted with some β-dicarbonyl compounds, such as ethyl acetoacetate, acetylacetone and ethyl β-arylazoacetoacetate, to yield the corresponding 2-(pyrazol-1-yl-carbonyl)thieno[2,3-b]pyridine derivatives 24, 25, and 27 respectively.     

Synthesis and photophysical properties of dinaphtho[2,3-b:2′,3′-i]dihydrophenazine derivatives

A dinaphtho[2,3-b:2′,3′-i]dihydrophenazine (DNP) derivative was synthesized by Buchwald-Hartwig cross-coupling, and its electronic spectrum was compared with that of dinaphtho[b,i]dihydrophenazine-5,18-dione (DNP-dione) as an anthraquinone analog. An absorption band of DNP is attributed to extension of π-conjugation over the entire molecule via the N atom. DNP-dione showed a broad absorption band in the range 450–490?nm due to intramolecular charge-transfer interactions. Additionally, the absolute fluorescence quantum yield of DNP was larger than that of DNP-dione. DNP-dione exhibited reversible oxidation peaks and a similar oxidation potential to DNP, since there are very weak electronic interactions between the anthracene and anthraquinone units across the N atoms with the 4-octyloxyphenyl substituent.     

Three-component synthesis of 1-substituted 6′,7′-dimethoxy-4′H-spiro[adamantane-2,3′-isoquinolines]

Russian Journal of Organic Chemistry -     

Synthesis and antitumor evaluation of novel tetrahydrobenzo[4′,5′]thieno[3′,2′:5,6]pyrimido[1,2-b]isoquinoline derivatives

In the present study, a novel 8,9,10,11-tetrahydro-7H,14H-benzo[4′,5′] thieno[2′,3′:4,5]-1,3-oxazino[3,2-b]isoquinoline-7,14-dione 5 was prepared by condensation of 2-amino-3-carbethoxy-4,5,6,7-tetrahydrobenzothiophene with homophthalic anhydride under microwave irradiation, followed by alkaline hydrolysis and cyclization using acetyl chloride. Compound 5 was further allowed to react with different nitrogen nucleophiles to get new tetrahydrobenzothienopyrimido isoquinolinone derivatives. The structures of the prepared compounds were elucidated by IR, ¹H-NMR, ¹³C-NMR, and mass spectroscopy. The newly prepared compounds were tested in vitro against a panel of two human tumor cell lines, namely, hepatocellular carcinoma (liver) HepG2, and mammary gland breast MCF-7. Almost all the tested compounds showed satisfactory activity.     

Synthesis and Crystal Structure of 3′-Ethyl 5′-Methyl 1-Benzyl-4′-methyl-2-oxo-3′,4′-dihydrospiro-[indoline-3,2′-pyrrole]-3′,5′-dicarboxylate

The crystal structure of the title compound(C24H24N2O5, Mr = 420.45) has been determined by single-crystal X-ray diffraction. The crystal is of triclinic, space group P1 with a = 8.991(1), b = 11.166(1), c = 11.169(1) , α = 91.413(2), β = 105.887(2), γ = 90.992(2)°, V = 1077.8(2) 3, Z = 2, Dc = 1.296 g/cm3, F(000) = 444, μ(MoKα) = 0.091 mm-1, the final R = 0.0466 and wR = 0.1507 for 4185 observed reflections(I 2σ(I)). The single-crystal X-ray diffraction data indicated intermolecular C(17)–H(17)O(4), C(5)–H(5)… O(4) hydrogen bonds and C–H…π interaction in the structure.     

Condensed isoquinolines 32. Synthesis of 4H-thieno-[3′,2′:5,6]-and-[2′,3′: 5,6]pyrimido-[1,2-b]isoquinolines and 6,12-dihydro-5H-isoquino-[2,3-a]quinazoline-5,12-dione derivatives

Treatment of 2-(4-oxo-3,4-dihydrothieno[2,3-d]-and-[3,2-d]pyrimidin-2-ylmethyl)benzoic acids and 2-(4-oxo-3,4-dihydro-2-quinazolinylmethyl)benzoic acid with acetic anhydride gave thieno[3′,2′:5,6]-and-[2′,3′:5,6]pyrimido[1,2-b]isoquinoline-4,11-diones and isoquino[2,3-a]quinazoline-5,12-dione respectively. NMR spectroscopy showed that an intramolecular acylation of the above acids occurs at the atom N-1 of the pyrimidinone part of the bicycle. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1053–1061, July, 2008.     

Vibrational spectra of the dithieno[3,2-b: 2′,3′-d] thiophene crystal

A normal mode analysis of dithieno[3,2-b:2′,3′-d]thiophene crystal was carried out using an intramolecular force field refined for the isolated molecule and an intermolecular potential described in terms of interactions among non-bonded atoms. Infrared and Raman data for internal and lattice vibrations are reported, including those for a deuterated isotopomer, which are satisfactorily accounted for by frequency calculations. Cartesian displacements for each normal mode of the isolated molecule are presented and frequency splittings and shifts analysed through calculations at k = 0 which include all crystal vibrational degrees of freedom.     

New convenient synthesis of substituted 6,9-dihydropyrido[3′,2′:4,5]thieno[3,2-b]pyridines and 6,9-dihydropyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines

1,4-Dihydro-3-cyano-2-pyridinethiolates react with 2-bromo-l-(4-bromophenyl)ethylidenemalononitrile or N-cyanochloracetanudine to give 6, 9-dihydropyrido[3, 2': 4, 5]thieno[3. 2-b]pyridines or 6, 9-dihydropyrido-[3.2:4.5Jthieno(3,2-d]pyrimidines, respectively.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 553–556, April, 1996.     

Synthesis of Dispiro[indoline-3,3′-pyrrolo[2,1-a]isoquinoline-1′,2′′-thiazolo[3,2-a]pyrimidine] Derivatives via Cycloaddition Reactions

Russian Journal of General Chemistry - The 1,3-dipolar cycloaddition reaction of ethyl (Z)-2-(2-methoxy-2-oxoethylidene)-7-methyl-3-oxo-5-aryl-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate...     

Photochromic and electrochromic properties of 1′,3′,3′-trimethyl-6-piperidino- and -morpholinospiro[indoline-2′,3-3H-naphtho[2,1-b][1,4]-oxazines]

Electrochromic properties of 1,3,3-trimethyl-6-piperidino- and-morpholinospiro[indoline-2,3-3H-naphtho[2,1-b][1,4]-oxazines] resulting from their ionization and the formation of intermediate products were studied. The characteristic features of the photochromic behavior of these compounds are positive solvatochromism for absorption spectra of a colored form and an increase in the rate constant for thermobleaching with increasing solvent polarity.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 836–838, May, 1994.