Synthesis and antimicrobial activity of new derivatives of pyrano[4',3':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidine and new heterocyclic systems

Taking into account previously obtained biological results on some polyheterocyclic compounds (containing different heteroatoms) and in particular on several 8-amino-5-isopropyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4’’,3’’:4’,5’]pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidines Ia-v we have carried out the synthesis of twentyone 8-amino-5-isobutyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4’’,3’’:4’,5’]pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidines 6. Therefore we have slightly modified the structure of the previously studied I introducing at C-5 an isobutyl group instead of the previously examined isopropyl ones in order to see if this variation (changing a little the lipophilicity) will affect the biological activity. Furthermore thieno[3,2-d]pyrimidine-8-thione 7 and their S-alkylated 8 were synthesized. Finally by alkylation of 5-isobutyl-2,2-dimethyl-10-thioxo-1,4,10,11-tetrahydro-2H-pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-8(9H)-one 3 with alkyl dichlorides (bifunctional reagents) we realized the cyclization of a thiazole or thiazine ring on the [b] side of the pyrimidine ring with formation of the new condensed pentaheterocyclic systems: pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d][1,3]thiazolo[3,2-a]pyrimidin-8-one 11 and pyrano[4''',3''':4'',5'']pyrido[3'',2'':4',5']thieno[3',2':4,5]pyrimido[2,1-b][1,3]thiazin-8-one 12. It was found that some of the synthesized compounds showed interesting antimicrobial activity (by agar diffusion method) against some gram-positive and gram-negative bacilli strains.     

2-[3-(Trifluoromethyl)phenyl]furo[3,2-b]pyrroles: synthesis and reactions

The synthesis and reactions of methyl 2-[3-(trifluoromethyl)phenyl]-4H-furo[3,2-b]pyrrole-5-carboxylate (1a) are described. Upon reaction with methyl iodide, benzyl chloride, or acetic anhydride, this compound gave N-substituted products 1b-d. By hydrolysis of compounds 1a-c, the corresponding acids 2a-c were formed, or by reaction with hydrazine-hydrate, the corresponding carbohydrazides 3a-c were formed. By heating 2-[3-(trifluoromethyl)phenly]-4H-furo[3,2-b]pyrrole-5-carboxylic acid (2a) in acetic anhydride, 4-acetyl-2-[3-(trifluoromethyl)phenyl]furo[3,2-b]pyrrole (4) was formed. By hydrolysis of 4, 2-[3-(trifluoromethyl)phenyl]-4H-furo[3,2-b]pyrrole (5a) was formed, and reactions with methyl iodide or benzyl chloride gave N-substituted products 5b-c. The reaction of 4 with dimethyl butynedioate gave substituted benzo[b]furan 6. Compound 3a reacted with triethyl orthoesters giving 7a-c, which afforded with phosphorus (V) sulphide the corresponding thiones 8a-c. The thiones 8a-c reacted with hydrazine hydrate to form hydrazine derivatives 9a-c. The reaction of triethyl orthoformiate with compounds 9a-c led to furo[2′,3′: 4,5]pyrrolo[1,2-d][1,2,4]triazolo[3,4-f][1,2,4]triazines 10a-c. Hydrazones 11a-c were formed from 3a-c and 5-[3-(trifluoromethyl)phenyl]furan-2-carboxaldehyde. The effect of microwave irradiation on some condensation reactions was compared with “classical” conditions. The results showed that microwave irradiation shortens the reaction time while affording comparable yields.     

Convenient synthesis of linear 2H,6H-pyrano[3,2-g] chromenes from natural occurring compound; visnagin

Abstract

A simple and convenient rout for the synthesis of linear 2-imino-2H,6H-pyrano[3,2-g] chromen-6-ones and 2H,6H-pyrano[3,2-g]chromene-2,6-diones has been described starting from natural occurring furochromone; visnagin (1). Ring opening of 1 yielded 6-formyl-7-hydroxy-5-methoxy-2-methylchromone (2), which underwent reaction with different acetonitrile derivatives furnished 2-imino-2H,6H-pyrano[3,2-g] chromen-6-ones (5a–h). Acid hydrolysis of 5a–h led to the formation of 2H,6H-pyrano[3,2-g]chromene-2,6-diones (6a–h). Structures of the synthesized compounds were clarified based on their elemental analyses and spectral data. The entire target compounds were selected for in vitro anticancer activity against 60 human cancer cell lines at a single dose (10^?5 M) by the National Cancer Institute (NCI, Bethesda, USA).     

Intramolecular 6-endo-dig-Cyclization of Ethyl 5-Aminomethyl-4-(1,2,3-thiadiazol-4-yl)furan-2-carboxylate

The reaction of 5-aminomethyl-4-(1,2,3-thiadiazol-4-yl)furan-2-carboxylic acid ethyl ester with bases has given ethyl 5-sulfanylidene-4,5,6,7-tetrahydrofuro[2,3-c]pyridine-2-carboxylate as a result of intramolecular 6-endo-dig-cyclization of thioketene generated in situ with an internal CH₂NH₂ nucleophile. The obtained ester has been alkylated with iodomethane at the sulfur atom to form ethyl 5-methylsulfanyl-4,7-dihydrofuro[2,3-c] pyridine-2-carboxylate. The Hantzsch reaction with ω-bromoacetophenone has resulted in the formation of 7-ethoxycarbonyl-3-phenylfuro[3,2-d[1,3]thiazolo[3,2-a]pyridin-4-ium bromide.

     

Pyrido[2,3-d]pyrimidines,II. One step synthesis of pyrido[2,3-d]pyrimidines and pyrimido[4,5-b]quinolines from 6-amino uracils

Summary Reduction of 6-azidouracils2 with hydrogen palladium or sodium dithionite afforded the corresponding 6-aminouracils5 which could also be obtained by reaction of2 with triphenylphosphanevia phosphazenes and subsequent hydrolysis (Staudinger reaction). The use of trimethylphosphite instead of phosphanes yields with2b the expected trimethoxyphosphazene3c, whereas2a reacts to the phosphonoaminopyrimidine4. The syntheses of 5-hydroxy pyrido[2,3-d]pryimidine-2,4,7-triones6, pyrido[2,3-d]pyrimidine-2,4,5-triones8, cyclopenta[e]pyrido[2,3-d]pyrimidin-2,4,5-triones7a,c, and tetrahydro-pyrimido[4,5-b]quinolin-2,4,5-triones7b,d by condensation of 6-aminouracils5 with malonates, ethylaceto/benzoylacetate, ethyl 2-oxocyclopentanecarboxylate and ethyl 2-oxocyclohexanecarboxylate, respectively, are described.

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Pyrido[2,3-d]pyrimidine, 2. Mitt. Einstufige Synthese von Pyrido[2,3-d]pyrimidinen und Pyrimido[4,5-b]chinolinen aus 6-Aminouracilen

Zusammenfassung Reduktion der 6-Azidouracile2 mit Wasserstoff/Palladium oder Natriumdithionit ergibt die entsprechenden 6-Aminouracile5, die auch durch Reaktion von2 mit Triphenylphosphin und anschließende Hydrolyse erhalten werden können (Staudinger-Reaktion). Die Verwendung von Trimethylphosphit anstelle von von Trimethylphosphin ergibt mit2b das erwartete Trimethoxyphosphazin3c, während2a zum Phosphonoaminopyrimidin4 reagiert. Die Synthesen der 5-Hydroxy-pyrido[2,3-d]pyrimidin-2,4,7-trione6, der Pyrido[2,3-d]pyrimidin-2,4,5-trione8, der Cyclopenta[e]pyrido[2,3-d]pyrimidin-2,4,5-trione7a,c und der Tetrahydro-pyrimido[4,5-b]chinolin-2,4,5-trione7b,d durch Kondensation der 6-Aminouracile5 mit Malonat, Acetat, Ethyl-2-oxocyclopentancarboxylat und Ethylcyclohexancarboxylat werden beschrieben.

     

Synthesis of 5,7-disubstituted-4-β-D-ribofuranosylpyrazolo[4,3-d]-pyrimidines and 2,4-disubstituted-1-β-D-ribofuranosylpyrrolo[3,2-d]-pyrimidines as congeners of uridine and cytidine

The synthesis of the congeners of uridine and cytidine in the pyrazolo[4,3-d]pyrimidine and pyrrolo[3,2-d]-pyrimidine ring system is described. Glycosylation of the trimethylsilyl (TMS) derivative of pyrazolo[4,3-d)pyrimidine-5,7(1H,4H,6H)-dione (4) with either 1-bromo- or 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose 5 and 6 , respectively in the presence of a Lewis acid catalyst gave the protected nucleoside 7 , which on debenzoylation afforded the uridine analogue 4-β-D-ribofuranosylpyrazolo[4,3-d]pyrimidine-5,7(1H,6H)-dione (8). Thiation of 7 gave 13 , which on deprotection yielded 4-β-D-ribofuranosyl-5-oxopyrazolo[4,3-d]pyrimidine-7(1H,-6H)-thione (14). Ammonolysis of 13 gave a low yield of the cytidine analogue 15. A chlorination of 7 , followed by amination furnished an alternative route to 15. A similar glycosylation of TMS-4 with 2,3,5-tri-O-benzyl-α-D-arabinofuranosyl chloride (16) gave mainly the N4 glycosylated product 17 , which on debenzylation furnished 4-β-D-arabinofuranosylpyrazolo[4,3-d]pyrimidine-5,7(1H,6H)-dione (18). 7-Amino-4-β-D-arabinofuranosylpyrazolo[4,3-d]pyrimidin-5(1H)-one (23) was prepared from 17 via the pyridinium chloride intermediate 21. Condensation of the TMS derivative of pyrrolo[3,2-d]pyrimidine-2,4(1H,3H,5H)-dione (24) with 6 , followed by deprotection of the reaction product gave 1-β-D-ribofuranosylpyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione (26). Similarly, TMS-24 was reacted with 16 to give a mixture of the blocked nucleosides 31 and 32 , which on debenzylation afforded a mixture of two isomeric compounds 34 and 35. 1-β-D-Arabinofuranosylpyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione (34) was converted to the ara-C analogue 38 via the 3-nitrotriazolyl intermediate 36. The structure of 38 was confirmed by single crystal X-ray diffraction studies.     

Studies on the chemistry of 5-propynyloxy- and 5-propynylthiopyrimidines: New syntheses of furo- and thieno[3,2-d]pyrimidines

The utility of certain 5-alkynyloxy-, 5-alkynylthio, and 5-alkynylsulfinyl-pyrimidines as precursors of 7-substituted furo[3,2-d]- and thieno[3,2-d]pyrimidines has been examined. When treated with sodium methoxide in warm methyl sulfoxide, 1,3-dimethyl-5-(2-propynyloxy)uracil ( 6 ) cyclizes to afford 1,3,7-tri-methylfuro[3,2-d]pyrimidine-2,4-(1H,3H)-dione ( 12 ) in 52% yield, possibly via the allenic ether 9 (R = H). The corresponding 5-(2-butynyloxy)pyrimidine ( 7 ), obtained in good yield by treating 6 with methyl iodide and sodium hydride in methyl sulfoxide, fails to undergo an analogous cyclization. However, compound 7 does undergo a normal alkynyl Claisen rearrangement and cyclization when heated at 130°, giving the 8-methylpyrano[3,2-d]pyrimidine 8 in methyl sulfoxide and the 6,7-dimethylfuro[3,2-d]pyrimidme 11 in dimethylformamide. The 5-(2-propynylthio)pyrimidine 15 affords the allene 19 and the 1-propyne 22 when treated with various bases, but none of the 7-methylthieno[3,2-d]pyrimidine 16. At 145° in methyl sulfoxide, 15 undergoes a thio-Claisen rearrangement process to afford the 6-methylthieno[3,2-d]pyrimidine 17 together with substantial amounts of a product 20 that bears a 7-thiomethoxymethyl substituent derived from the solvent. Heating the 5-(2-propynylsulfinyl)pyriniidine 23 at 105° in methyl sulfoxide, followed by acidification of the reaction mixture, affords 1,3-dimethyl-7-formylthieno[3,2-d]pyrimidine-2,4-(1H,3H)-dione ( 29 ) in 47% yield. Deuterium labelling studies established that the aldehyde proton of 29 is derived from the 3′-proton of 23 . This finding is consistent with a mechanism that involves sequential [2,3] and [3,3] sigma-tropic rearrangements, and the intermediacy of a dihydrothieno[3,2-d]pyrimidine such as compound 30.     

[1]Benzothienopyrimidines. I. Etude de la 3H-benzothieno[3,2-d]pyrimidone-4

3H-benzothieno[3,2-d]pyrimidin-4-one (3) was synthesized by bimolecular cyclising the 3-amino-2-carbethoxybenzothiophene (1) with formamide. The electrophilic substituion of 3 afforded N-methylated lactam derivavtives, the structure of which was assigned by 'H nmr and unequivocal synthesis. The sysnthesis of benzothieno[3,2-d]pyrimidine (7) was achieved by desulphurization of the 3H-benzothieno[3,2-d]-[3,2-d]pyrimisine-4-thione (6) or by oxydation of the 4-hydrazinobenzothieno[3,2-d]primidine (5).     

Synthesis and Reactions of 4-Oxiranylmethylfuro[3,2-b]pyrroles and Their Benzo Derivatives

Methyl 4-oxiranylmethyl-4H-furo[3,2-b]pyrrole-5-carboxylates 2a-c and methyl 1-oxiranylmethyl-1H-benzo[4,5]furo[3,2-b]pyrrole-2-carboxylate (2d) were prepared by reaction of the appropriate starting compounds 1a-d with excess chloromethyloxirane. The compounds 2a-d undergo oxirane ring opening by heterocyclic amines (morpholine, pyrrolidine, piperidine or 4-methylpiperazine) giving N-2-hydroxy-3-heteroaminopropyl-substituted compounds 3a-f or substituted 4,5-dihydrofuro[2',3':4,5]pyrrolo[2,1-c][1,4]oxazin-8-ones 4a-e.     

Synthesis and reactions of 2,3-dimethylfuro[3,2-c]pyridines

Summary A number of substituted 2,3-dimethylfuro[3,2-c]pyridines was synthesized. 3-(4,5-Dimethyl-2-furyl)propenoic acid (1) was converted to the acid azide2, which in turn was cyclized to give 2,3-dimethyl-5H-furo[3,2-c]pyridine-4-one (3) by heating at 240°C in Dowtherm. The pyridone3 was chlorinated with phosphorus oxychloride to give4, which was reduced with zinc and acetic acid to 2,3-dimethylfuro[3,2-c]pyridine (5). Treatment of4 with several secondary heterocyclic amines led to compounds6a–6c. Reaction of pyridone3 with phosphorus pentasulfide rendered the thione7, which was methylated to8a. The 4-methoxy derivative8b was obtained from4 with sodium methoxide. 2,3,5-Trimethylfuro[3,2-c]pyridine-4-one (9) was obtained by reaction of3 with methyl iodide.Dedicated to Professor Dr.Fritz Sauter on the occasion of his 65th birthday     

Synthesis of 5H-Triazolo[1,5-d]- and 5H- Tetrazolo- [1,5-d]thieno[3,2-f]-1,4-diazepin-6(7H)-ones

5H-Triazolo[1,5-d]- and 5H-tetrazolo[1,5-d]thieno[3,2-f]-1,4-diazepin-6(7H)-ones have been obtained by the base catalysed ring expansion reaction of 5-chloromethyl-1,2,4-triazolo[1,5-c]- and 5-chloromethyltetrazolo- [1,5-c]thieno[3,2-e]pyrimidines. The required thienopyrimidine derivatives were synthesized from 2-amino-3-triazolyl- and 2-amino-3-tetrazolylthiophenes by acylation, followed by dehydrative cyclization.     

New heterocyclic structures. [1,3]Thiazino[3,2-a]purine and [1,2,3]triazolo[4,5-d][1,3]thiazino[3,2-a]pyrimidine

Derivatives of two new molecular structures, namely, [1,3]thiazino[3,2-a]purine and [1,2,3]triazolo[4,5-d]-[1,3]thiazino[3,2-a]pyrimidine, were synthesized together with other heterocyclic compounds. Retrosynthetic analysis of their molecular skeletons suggested a simple way of obtaining 3,4-dihydro-7,8-diamino-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-one, which is a useful intermediate for their synthesis. This intermediate and the thiazole homologue were obtained directly by reaction of 5,6-diamino-2,3-dihydro-2-thioxo-4(lH)-pyrimidi-none with 1,3- or 1,2-dibromoalkane, respectively.     

A new synthesis of pyrimido[5,4-e]-as-triazine 4-oxides and their ring transformation to pyrrolo[3,2-d]pyrimidines

A new synthesis of certain pyrimido[5,4-e]-as-triazine 4-oxides and their ring transformation to pyrrolo-[3,2-d]pyrimidines by the 1,3-dipolar cycloaddition reaction is described. Thus, reaction of 6-hydrazino-1,3-dimethyluracil ( 1 ) with triethyl orthoformate gave 6-ethoxymethylenehydrazino-1,3-dimethyluracil ( 2 ). Treatment of 2 with arylamines gave 6-arylaminomethylenehydrazino-1,3-dimethyluracils ( 3a-e ). Nitrosative cyclization of 3a-e with sodium nitrite afforded 3-arylaminofervenulin 4-oxides ( 6a-e ). Reaction of 6a-e with acetylenic esters yielded 7-alkoxycarbonyl-6-arylamino-1,3-dimethylpyrrolo[3,2-d]pyrimidine-2,4(1H,3H-diones ( 15a-e and 16 ).     

9-deazapurine nucleosides. The synthesis of certain N-5-2′-deoxy-β-D-erythropentofuranosyl and N-5-β-D-arabinofuranosylpyrrolo[3,2-d]pyrimidines

A number of 2,4-disubstituted pyrrolo[3,2-d]pyrimidine N-5 nucleosides were prepared by the direct glycosylation of the sodium salt of 2,4-dichloro-5H-pyrrolo[3,2-d]pyrimidine (3) using 1-chloro-2-deoxy-3,5-di-O-(p-toluoyl)-α-D -erythropentofuranose (1) and 1-chloro-2,3,5-tri-O-benzyl-α-D-arabinofuranose (11) . The resulting N-5 glycosides, 2,4-dichloro-5-(2-deoxy-3,5-di-O-(p-toluoyl) -β-D-erythropentofuranosyl)-5H-pyrrolo-[3,2-d]pyrimidine (4) and 2,4-dichloro-5-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl-5H -pyrrolo [3,2-d)pyrimidine (12) , served as versatile key intermediates from which the N-7 glycosyl analogs of the naturally occurring purine nucleosides adenosine, inosine and guanosine were synthesized. Thus, treatment of 4 with methanolic ammonia followed by dehalogenation provided the adenosine analog, 4-amino-5-(2-deoxyerythropentofuranosyl) -5H-pyrrolo[3,2-d]pyrimidine (6) . Reaction of 4 with sodium hydroxide followed by dehalogenation afforded the inosine analog, 5-(2-deoxy-β-D-erythropentofuranosyl) -5H-pyrrolo[3,2-d]pyrimidin-4(3H)-one (9) . Treatment of 4 with sodium hydroxide followed by methanolic ammonia gave the guanosine analog, 2-amino-5-(2-deoxy-β-D-erythropentofuranosyl) -5H-pyrrolo[3,2-d]pyrimidin-4(3H)-one (10) . The preparation of the same analogs in the β-D-arabinonucleoside series was achieved by the same general procedures as those employed for the corresponding 2′-deoxy-β-D-ribonucleoside analogs except that, in all but one case, debenzylation of the sugar protecting groups was accomplished with cyclohexene-palladium hydroxide on carbon, providing 4-amino-5-β-D-arabinofuranosyl-5H-pyrrolo [3,2-d]pyrimidin-4(3H)-one (18) . Structural characterization of the 2′-deoxyribonucleoside analogs was based on uv and proton nmr while that of the arabinonucleosides was confirmed by single-crystal X-ray analysis of 15a . The stereospecific attachment of the 2-deoxy-β-D-ribofuranosyl and β-D-arabinofuranosyl moieties appears to be due to a Walden inversion at the C₁ carbon by the anionic heterocyclic nitrogen (S_N2 mechanism).     

New syntheses of pyrido[3,2-d]pyrimidines

New synthetic routes to pyrido[3,2-d]pyrimidines starting with 5-amino-1,3,6-trimethyluracil (I) or 1,3,6-trimethyl-5-nitrouracil (X) are described. Thus, condensation of I with arylaldehydes gave 5-arylideneamino-1,3,6-trimethyluracils (IIa-h), which upon heating with dimethylformamide dimethylacetal afforded 6-aryl-1,3-dimethylpyrido[3,2-d]pyrimidine-2,4(1H,3H)-diones (Va-h) via 5-arylideneamino-1,3-dimethyl-6-(2-dimethylaminovinyl)uracils (IIIa-h). On the other hand, reaction of X with phenylacetaldehyde in the presence of base yielded Va and its 5-oxide (XI).     

[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.     

Synthesis and antimicrobial testing of 2-amino-6-hydroxymethyl-4-(3H)pyrido[3,2-d]pyrimidinone

Synthesis of 2-amino-6-hydroxymethyl-4-(3H)pyrido[3,2-d]pyrimidinone ( 5 ) from 2-amino-6-methyl-4-(3H)-pyrido[3,2-d]pyrimidinone ( 2 ) was accomplished by selenium dioxide oxidation of 2 to the aldehyde 4 followed by sodium borohydride reduction. Compound 2 was available in four steps from 5-aminouracil or in two steps from 5-nitroisocytosine ( 3a ). Catalytic reduction of 4 or 5 gave a mixture of 2-amino-6-methyl-5,6,7,8-tetrahydro-4-(3H)pyrido[3,2-d]pyrimidinone ( 6a ) and the 6-hydroxymethyl compound 6b . These compounds showed only weak inhibitory activity in the coupled reactions catalyzed by 7,8-dihydro-6-hydroxymethylpterin pyrophosphokinase and 7,8-dihydropteroate synthetase from E. Coli. No significant antibacterial activity was observed.     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones. XIII. Synthesis of 2H-pyrano[3,2-d]-1-benzoxepin derivatives

Cycloaddition of dichloroketone to N,N-disubstituted (E)-4-aminomethylene-3,4-dihydro-1-benzoxepin-5(2H)-ones gave N,N-disubstituted 4-amino-3,3-dichloro-3,4,5,6-tetrahydro-2H-pyrano[3,2-d]-1-benzoxepin-2-ones II, which are derivatives of the new heterocyclic system 2H-pyrano[3,2-d]-1-benzoxepin. Dehydrochlorination with triethylamine of II afforded N,N-disubstituted 4-amino-3-chloro-5,6-dihydro-2H-pyrano-[3,2-d]-1-benzoxepin-2-ones III in good to moderate yields. In the triethylamine treatment of IIh (NR₂ = diphenylamino), 3-chloro-5,6-dihydro-2H-pyrano[3,2-d]-1-benzoxepin-2-one was isolated in low yield near to IIIh, whereas IIc (NR² = diisopropylamino) gave in low yield 4-diisopropylamino-5,6-dihydro-2H-pyrano(3,2-d)-1-benzoxepin-2-one.     

4,6-Diacetylresorcinol in Heterocyclic Synthesis,Part I: Synthesis and Biological Evaluation of Some New Linearly and Angularly Substituted Pyrano[3,2-g] Chromenes via Vilsmeier–Haack Formylation of 4,6-Diacetylresorcinol,Its Schiff Bases,and Hydrazones

Application of Vilsmeier–Haack reaction on 4,6-diacetylresorcinol (1) led to the formation of 4,6-dioxo-4H,6H-pyrano[3,2-g]chromene-3,7-dicarboxaldehyde (2) in good yield. The dicarboxaldehyde 2 was condensed with some carbon and nitrogen nucleophiles. Some aliphatic and aromatic Schiff bases of 4,6-diacetylresorcinol (1) were subjected to Vilsmeier–Haack formylation reaction to afford 4,6-bis(alkyl/arylimino)-4H,6H-pyrano[3,2-g]chromene-3,7-dicarbaldehydes 10, 14, and 15. Also, treatment of some bis-hydrazones of 4,6-diacetylresorcinol 16–19 with Vilsmeier–Haack reagent afforded the corresponding 4,6-bis(4-formylpyrazol-3-yl)resorcinols 20 and 21, which underwent oxidation with iodine to yield the pyrano[3,2-g]chromeno[4,3-c:7,6-c]dipyrazole-4,8-diones 22 and 23, respectively. Most of the synthesized compounds revealed weak antimicrobial activities. It was noticed that the dicarboxaldehydes 2, 10, 14, and 15 exhibited moderate antibacterial activity against Gram-positive bacteria, yeast, and fungus.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

The reaction of 2-amino-7-methyl-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]-pyrimidine with carbon disulfide and alkylation of its products

In the reaction with carbon disulfide, 2-amino-7-methyl-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine (1) forms the alkaline salts of substituted dithiocarbamic or iminodithiocarbonic acids depending on the molar ratio between1, CS₂, and the alkali. The alkylation of these salts leads to the esters ofN-(7-methyl-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-2-yl)dithiocarbamic (2) and diesters of (7-methyl-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-2-yl)iminodithiocarbonic acids (3). The synthesis of asymmetric diesters3 may be fulfilled based on monoesters2.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 14–14, August, 1994.