Interaction of 4,5,7-Trimethyl-4,5,6,7-tetrahydropyrrolo[3,2-<Emphasis Type="Italic">c</Emphasis>]pyridines with Acetic and Trifluoroacetic Anhydrides

The reactions of NH- and N-vinyl-4,5,7-trimethyl-4,5,6,7-tetrahydropyrrolo-[3,2-c]pyridines and their 2-substituted derivatives with acetic and trifluoroacetic anhydrides have been studied. Trifluoroacetylation of tetrahydropyrrolo-[3,2-c]pyridines occurs at the α-position of the pyrrole ring, whereas cleavage of the tetrahydropyridine ring with formation of 3-vinylpyrroles occurs with acetic anhydride. 2-Acetyl-4,5,7-trimethyl-1-vinyl-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridine was synthesized by the Vilsmeier-Haack reaction.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, 751–760. May, 2005.     

Five new peltogynoids from underground parts of Iris bungei: a Mongolian medicinal plant

Five new peltogynoids, irisoids A-E (1-5), have been isolated from the underground parts of Iris bungei. The structures of the new compounds were established on the basis of spectroscopic methods and were found to be 1,8,10-trihydroxy-9-methoxy-[1]benzopyrano-[3,2-c][2]-benzopyran-7(5H)-one (1), 1,8-dihydroxy-9,10-dimethoxy-[1]benzopyrano-[3,2-c][2]-benzopyran-7(5H)-one (2), 1,10-dihydroxy-8,9-dimethoxy-[1]benzopyrano-13,2-c][2]-benzopyran-7(5H)-one (3), 1,8-dihydroxy-9,10-methylenedioxy-[1]benzopyrano-[3,2-c][2]-benzopyran-7(5H)-one (4), and 1,8,11-trihydroxy-9,10-methylenedioxy-[1]benzopyrano-[3,2-c][2]-benzopyran-7(5H)-one (5). The structure of irisoid B (2) was established unambiguously by X-ray diffraction study.     

Thermal properties of solid complexes with biologically important heterocyclic ligands

The stoichiometry of thermal decomposition of the complexes Co(NCS)₂(fpy)₄ (I), Co(NCS)₂(Mefpy)₄ (II) and Co(NCS)₂(bfpy)₄ (III) (where fpy = furo[3,2-c]pyridine, Mefpy = methylfuro[3,2-c]pyridine, bfpy = benzo-[2, 3]furo[3,2-c]pyridine) have been investigated in nitrogen atmosphere from room temperature (RT) to 800 °C by means of TG and DTA. The results revealed that release of heterocyclic ligands occurs in one step. Infrared data suggested that fpy, Mefpy and bfpy were coordinated to Co(II) through the nitrogen atom of the respective heterocyclic ring and anionic ligands through nitrogen atom of the NCS groups.     

Nouvelles voies d'accès à des aryl-4 thiéno[2,3-c]pyridines et à des aryl-7 thiéno[3,2-c]pyridines

4-Arylthieno[2,3-c]pyridines and 7-arylthieno[3,2-c]pyridines have been prepared by heating in polyphosphoric acid 2-(2-thenylamino>l-arylethanols or propanols and 2- 3-thenylamino>l-arylethanols or propanols, respectively.) Under the Beckmann rearrangement conditions, oximes of 4-aryl-4,5-dihydro-6H-cyclopenta[b]thiophen-6-one lead to 4-aryl-4,5- dihydro-6H-thieno[2,3-c]pyridin-7-one.     

Sesquiterpenoid derivatives from Ferula ferulaeoides [correction of ferulioides]. V

Nine novel prenyl-dihydrofurocoumarin-type sesquiterpenoid derivatives, 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadien-6-onyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4-methyl-5-(4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4-methyl-5- (4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadien-6-onyl]-furo-[3,2-c]coumarin, and 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4-methyl-5-(4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, were isolated from the roots of Ferula ferulaeoides [corrected]. The structures were established by comprehensive spectral analysis. The biosynthetic pathway leading to these prenyl-furocoumarin-type sesquiterpenoids is proposed based on their structures.     

Acetals of lactams and acid amides. 35. Synthesis of condensed two- and three-ring pyridine systems on the basis of enamino amides

The synthesis of 2,3,5,6-tetrahydropyrrolo[3,2-c]pyrid-6-one was accomplished by rearrangement of 8H,1-cyano-8-dimethylaminomethylene-2,5,6,7-tetrahydropyrrolo[1, 2-c]pyrimidine. Pyrrolo[3,2-c]pyrimidine, 1,6-naphthyridine, and pyrimido[4,3-b]-azepine derivatives were synthesized on the basis of enamino dinitriles. The hydrolysis of 8H,1-cyano-8-dimethylaminomethylene-2,5,6,7-tetrahydropyrrolo[1,2-c]-pyrimidine in 50% CH₃COOH leads to a pyrrolo[1,2-c]pyrido[4,3-d]pyrimidine derivative. A similar dipyrido[4,3-d-1,2-c]pyrimidine derivative was obtained from 1-cyano-9-dimethylaminomethylene-2,5,6,7,8,9-hexahydropyrido[1,2-c]pyrimidine under these conditions, and 3,4-dioxo-3,4,7,8,9,10-hexahydropyrido[1,2-c]pyrano[4,3-d]-pyrimidine was synthesized bytreatment with a 1 N solution of HCl.See [1] for Communication 34.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 518–522, April, 1982.     

Heterocyclic quinones. XIV. Pharmacomodulation in a series of 11H-indolo[3,2-c]quinolinediones: synthesis and cytotoxicity of 8-substituted 11H-indolo[3,2-c]quinoline-7,10-diones

4-Chloro-8-methoxy-11H-indolo[3,2-c]quinoline could be obtained from 8-chloro-2,3-dihydro-1H-quinolin-4-one and 4-methoxyphenylhydrazine by applying Fischer's indole synthesis. Its nitration led to the 7-nitro derivative which was reduced to 7-amino-4-chloro-8-methoxy-11H-indolo[3,2-c]quinoline when Raney nickel was employed as a catalyst and to 7-amino-8-methoxy-11H-indolo[3,2-c]quinoline when palladium charcoal was used. Oxidation of the amines by potassium nitrosodisulfonate produced the corresponding 11H-indolo[3,2-c]quinoline-7,10-diones. Displacement of the methoxy group by (N,N-diethylamino)ethylamine or by N-methylpiperazine afforded the 8-aminoquinones. The quinones unsubstituted at the 4-position were more cytotoxic than the previously described 2-methoxy-11H-indolo[3,2-c]quinoline-1,4-diones.     

Two efficient cascade reactions to synthesize substituted furocoumarins

We have developed two efficient one-pot reactions to generate furo[3,2-c]coumarins and chlorofuro[3,2-c]coumarins through addition/cyclization/oxidation and chlorination. One cascade addition/cyclization/oxidation sequence of 1 with H(2)O in the presence of 20% CuCl as Lewis acid under an air atmosphere generated the 2-substituted-4 H-furo[3,2-c]chromen-4-one 2. Another sequence in the presence of 10% CuBr and excess CuCl(2) as the oxidant afforded the 3-chloro-2-substituted-4 H-furo[3,2- c]chromen-4-one 3.     

Synthesis and pharmacological evaluation of 5-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine derivatives as platelet aggregation inhibitors

One pot synthesis and characterization of new 5-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridines (3a–k) using amides (2a–k) were reported. The prepared 5-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine (3a) is a bioisostere of 4′-(6,7-dihydro-4H-thieno [3,2-c]pyridin-5-ylmethyl)-biphenyl-2-carboxylic acid (1), having good in vivo antithrombotic activity compared with Clopidogrel. The new tetrazole derivatives (3a–k) were screened for their in vitro activity as platelet aggregation inhibitors.     

Studies on Quinazolines. Part III. Synthesis of Some Fused-Ring Cationic and Mesoionic Derivatives of the 1,3-Thiazolo[3,2-c]quinazoline Ring System

4-Allylthio-2-arylquinazolines 4a–c undergo cyclization by action of bromine to furnish 5-aryl-3-bromomethyl-2,3-dihydrothiazolo[3,2-c]quinazolin-4-ium bromide 5a–c. Compounds 5a–c undergo ring opening by action of water under acid catalysis to afford the corresponding dibromide derivatives 6a–c. Bromination of 3-allyl-2-aryl-4(3H)quinazolinethiones 7a–c leads to 5-aryl-2-bromomethyl-2,3-dihydrothiazolo[3,2-c]quinazolin-4-ium bromides 8a–c. However, 5-aryl-1,3-thiazolo[3,2-c]quinazolinium-3-olate 10a–c were prepared by the cyclodehydration of the corresponding thioglycolic acids 9a–c with Ac₂O.     

A Convenient Synthesis of Novel Functionalized Pyrimido[5′,4′:4,5]thieno[3,2-c]pyridazines and Related Fused Systems

Possible approaches to the synthesis of functionalized, pyrimido[5′,4′:4,5]thieno [3,2-c]pyridazines 2-18 , pyridazino[3′,4′:4,5]thieno[2,3-d]triazines 19, 20a,b and pyrido[3′,2′:4,5]thieno[3,2-c]pyridazines 22a,b are described. The sequence involves the heterocyclization of 6-amino-1,3-diphenyl-1,4-dihydrothieno[3,2-c]pyridazine-7-carboxamide (1) with appropriate reagents. The antimicrobial activity of some the newly synthesized compounds was examined. All tested compounds proved to be active as antibacterial and antifungal agents.     

Crystal structure, spectroscopic and magnetic properties, and antimicrobial activities of cobalt(II) 2-methylthionicotinate complexes with N-heterocyclic ligands

Synthesis and characterization of 10 new 2-methylthionicotinate (2-MeSnic) Co(II) complexes, namely, [Co(2-MeSnic)₂L₂(H₂O)₂] · nH₂O (L is N,N-diethylnicotinamide—Et₂nia, ethylnicotinate—Etnic, nicotinamide—nia, isonicotinamide—isonia, N-methylnicotinamide—N-Menia, furo[3,2-c]pyridine—fpy, 2,3-dimethylfuro[3,2-c]pyridine—Me₂fpy or benzo[4,5]furo[3,2-c]pyridine—Bfp; n is 0, 1 or 2) as well as [Co(2-MeSnic)₂L₂] (L is ronicol—ron or 2-methylfuro[3,2-c]pyridine—Mefpy), are reported. The characterizations were based on physico-chemical and spectroscopic methods. The crystal structure of one of the complexes has been determined. In the molecular complex [Co(2-MeSnic)₂(Me₂fpy)₂(H₂O)₂], the Co(II) central atom, located at a symmetry centre, is octahedrally coordinated by an oxygen atom of the unidentate 2-MeSnic carboxyl group, the nitrogen atom of the pyridine ring of Me₂fpy, a water molecule and the corresponding centrosymmetrically located atoms. Also, biological activity of the complexes against various strains of bacteria and filamentous fungi has been investigated. It is concluded that by complexation of these nicotinate derivatives their biological activities are elevated. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Derivatives of the androstane series

Conclusions 1. The synthesis of 17-hydroxyandrostano[3,2-c]pyrazole and of cholestano[3,2-c]pyrazole has been effected by the reaction of the corresponding 2-hydroxymethylene-3-oxosteroids with hydrazine hydrate.2. The mechanism of the formation of these pyrazoles has been studied. It has been shown that the reaction takes place in two stages, regardless of the substituent at C₁₇ of the steroid molecule, with the formation of the 2-hydroxymethylene-3-hydrazone and its dehydration to form the pyrazole derivative.Khimiya Prirodnykh Soedinenii, Vol. 6, No. 1, pp. 31–33, 1970     

[1]Benzofuro[3,2-<Emphasis Type="Italic">c</Emphasis>]pyridine synthesis and coordination reactions

(E)-3-(1-Benzofuran-2-yl)propenoic acid (1) was prepared from 1-benzofuran-2-carbaldehyde under the Doebner’s conditions. The obtained acid was converted to the corresponding azide 2, which was cyclized by heating in diphenyl ether to [1]benzofuro[3,2-c]pyridine-1(2H)-one (3). This compound was aromatized with phosphorus oxychloride to chloroderivative 4 which was reduced with zinc and acetic acid to the title compound 5. [1]Benzofuro[3,2-c]pyridine-2-oxide (6) was synthesized by reaction of 5 with 3-chloroperoxybenzoic acid in dichloromethane. Treatment of 6 with benzoyl chloride and potassium cyanide (Reissert-Henze reaction) was shown to produce the corresponding [1]benzofuro[3,2-c]pyridine-1-carbonitrile (7). The title compound was used for preparation of complexes Cu₂(ac)₄(bfp)₂ (8) and CoCl₂(bfp)₂ (9), where ac=CH₃CO₂⁻ and bfp=[1]benzofuro[3,2-c]pyridine. Both oxygen atom of carboxylate ions is used in the coordination to Cu(II). Thermal properties of the complexes 8 and 9 have been studied by TG and DTA and both complexes exhibited high thermal stability while complex 9 are thermally more stable than complex 8.     

Some reactions of 3-halogenocinnolines catalysed by palladium compounds

3-Bromo- or 3-iodo-cinnoline (and 4-substituted analogues) are condensed with terminal alkynes in the presence of Pd and Cu compounds as catalysts to give the 3-alkynyl-derivatives. When 4-chloro- or 4-phenoxy-compounds are used, the products react with amines, in the presence of copper(I) iodide, to form pyrrolo[3,2-c]cinnolines and with hydrazines to give either the same ring system or a pyrazolo[4,3-c]cinnoline. Hydrolysis of 3-alkynyl-4-phenoxycinnoline to 3-alkynyl-4(1H)-cinnoline, followed by cyclisation, yields the furo[3,2-c]cinnoline. Attempts to condense 3-halogenocinnolines with alkenes gave variable results: 3-phenyl ethenyl- and 3(2-pyridylethenyl)-4-(1H)-cinnolinones were obtained but 3-bromocinnoline gave the 3,3′-bicinnolinyl. Action of palladium acetate in the presence of ethyl acrylate converted 3-bromo-4-phenoxycinnoline into benzofuro[3,2-c]cinnoline and 3-bromo-4-phenylaminocinnoline into indolo[3,2-c]cinnoline.     

Reactions of 5-[3-(trifluoromethyl)-phenyl]furan-2-carbaldehyde

The Knoevenagel condensations of 5-[3-(trifluoromethyl)phenyl]furan-2-carbaldehyde with seven compounds containing an active methyl or methylene group have been studied. The compounds used were: methyl 2-cyanoacetate, malononitrile, 2-furylacetonitrile, acetophenone, 2-thioxo-1,3-thiazolidin-4-one (rhodanine), 5,5-dimethylcyclohexane-1,3-dione (dimedone), and methyl 2-azidoacetate. The effect of microwave irradiation on the condensation reactions was studied and compared with “’classical”’ conditions. Thermolysis of methyl 2-azido-3-{5-[3-(trifluoromethyl)phenyl]-2-furyl}propenoate afforded methyl 2-[3-(trifluoromethyl)phenyl)]-4H-furo[3,2-b]pyrrole-5-carboxylate. (2E)-3-{ 5-[3-(Trifluoromethyl)phenyl]-2-furyl}propenoic acid was converted to the corresponding azide, which was cyclized on heating into 2-[3-(trifluoromethyl)phenyl)]-4,5-dihydrofuro[3,2-c]pyridin-4-one. The latter after successive action of POCl₃ and NH₂NH₂-Pd/C gave 2-[3-(trifluoromethyl)-phenyl]furo[3,2-c]pyridine. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 825–831, June, 2006.     

2-Dichloromethyl-4-methyl-2,3-dihydrofuro[3,2-c]-quinoline derivatives

Substituted 2-dichloromethyl-4-methyl-2,3-dihydrofuro[3,2-c]quinolines were obtained by cyclization of substituted 2-methyl-3-(3,3-dichloroallyl)-4-hydroxquinolines, and 2-dichloromethyl-2,4-dimethyl-2,3-dihydrofuro[3,2-c]quinolines were isolated from 2-methyl-3-(2-methyl-3,3,dichloroallyl)-4-hydroxyquinolines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 84–86, January, 1973.     

Sesquiterpenoid derivatives from Ferula ferulaeoides [correction of ferulioides]. IV

Four novel prenyl-furocoumarin type sesquiterpenoid derivatives, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-3-[4,8-dimethyl-3(E),7-nonadie nyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-3-[4,8-dimethyl-3(E),7-nonadie nyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-3-[4-methyl-5-(4-methyl-2-furyl)- 3(E)-pentenyl]-furo[3,2-c]coumarin, and 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-3-[4,8-dimethyl-3(E),7-nonadie nyl]-furo]3,2-c]coumarin were isolated from the roots of Ferula ferulaeoides [corrected]. Their structures were established by detailed spectral analysis and the biosynthetic pathway leading to these prenyl-furocoumarin type sesquiterpenoids is proposed based on these structures.     

Nouvelle méthode d'accès aux benzo[h]furo[3,2-c]quinoléines,analogues isostériques des benzo[c]phénanthridines

A convenient synthesis of the benzo[h]furo[3,2-c]quinoline ring is reported. Hydrogenation of dienic adducts 5 gives comppounds 6. Successive pyrolysis and alcaline hydrolysis of 6 provide diacids 9 which in the presence of anhydrous ammonium acetate and acetic acid undergoes intramolecular cyclisation to give benzo[h]furo[3,2-c]quinolone derivatives 12. The modulation of the 7-carboxy group and introduction of amino groups in the 6 position are then realized.     

Synthesis and nitration of NH- and N-vinyl-4,5,7-trimethyl-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridines

It has been shown that the most efficient catalysts for the synthesis of 4,5,7-trimethyl-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridine from 1,2,5-trimethylpyridin-4-one and acetylene under Trofimov conditions are rubidium and potassium hydroxides. Use of Triton B or a mixture of trimethylbenzylammonium chloride with rubidium hydroxide as catalyst gives O-alkylated oxime. Their configurations and conformations were established through separation of the individual isomers of 1-vinyl-4,5,7-trimethyl-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridines. Acetyl nitrate nitration of the cis isomer of this compound gave the 2- and 3-nitro derivatives. Similar nitration of 4,5,7-trimethyl-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridine gave the 2-nitro-7-hydroxy derivative.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1375–1380, October, 1991.