Pyridine-2(1H)-thione in heterocyclic synthesis: synthesis and antimicrobial activity of some new thio-substituted ethyl nicotinate,thieno[2,3-b]pyridine and pyridothienopyrimidine derivatives

3-(4-Bromophenyl)-2-cyanoprop-2-enethioamide (1) reacted with ethyl 3-oxo-3-phenylpropanoate (2) to give ethyl 4-(4-bromophenyl)-5-cyano-2-phenyl-6-thioxo-1,6-dihydropyridine-3-carboxylate (3). Compound 3 was taken as a starting material for the synthesis of thio-substituted ethyl nicotinate derivatives 5a–d, which underwent cyclization to the corresponding thieno[2,3-b]pyridines 6a–d. Also 3 reacted with hydrazine hydrate to give the pyrazolo[3,4-b]pyridine derivative 7, which upon diazotization gave the diazonium derivative 8. Compound 6a condensed with dimethylformamide–dimethylacetal to afford thieno[2,3-b]pyridine derivative 9, which reacted with different amines 10a–e to afford the pyridothienopyrimidine derivatives 12a–e through the Dimroth rearrangement. Moreover, compound 6a reacted with different reagents to give pyridothienopyrimidine derivatives 14a and b, 17 and pyrazolothienopyridine derivative 18. In addition, acetylating compound 6c with chloroacetylchloride afforded the 3-[(2)-chloroacetylamino]thieno[2,3-b]pyridine derivative 20, which upon cyclization yielded the corresponding 2-chloromethylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine derivative 21. Some of the newly synthesized compounds were screened in vitro for their antimicrobial activities.

     

A novel synthesis of indeno[2',1': 5,6] pyrido[2,3- d ][1,2,4]triazolo[4,3- a ]pyrimidines

Reaction of 5-(4-chlorophenyl)-2-thioxo-2,3-dihydro-1H-indeno[2',1':5,6] pyrido[2,3-d]pyrimidine-4,6-dione with hydrazonoyl chlorides gave 1,2,4-triazolo[4,3-a]pyrimidine derivatives regioselectively in good yields. The structures of the newly synthesized compounds are established on the basis of chemical and spectroscopic evidence as well as their synthesis by alternative methods.     

An efficient microwave-assisted synthesis of thieno[2,3- b ]quinolines under solvent-free conditions

A novel and efficient method for the synthesis of substituted thieno[2,3-b]quinolines has been developed. A simple one-pot reaction of 3-formyl-2-mercaptoquinolines 2a–l with 1-chloroacetone, 2-chloroacetamide, ethyl chloroacetate and 2-chloro-1-phenylethanone in presence of catalytic amount of potassium carbonate under microwave irradiation and solvent-free conditions gave thieno[2,3-b]quinolin-2-ylethanone derivatives 3a–e, thieno[2,3-b]quinoline-2-carboxamide derivatives 4a–e, ethyl thieno[2,3-b]quinoline-2-carboxylate 5a–e and phenyl(thieno[2,3-b]quinolin-2-yl)methanone derivatives 6a–e compounds respectively. The structures of all the newly synthesised compounds were elucidated on the basis of elemental analysis, IR, ¹H NMR and mass spectral data.     

Two-component,one-pot synthesis of pyrimido[1,2-b] [1,2,4,5]tetrazines

Derivatives containing the cyclohepta4′,5′thieno[2′,3′:4,5]pyrimido[1,2-b][1,2,4,5]-tetrazin-6-one system were prepared from the reaction of 3-amino-2-thioxo-1,2,3,5,6,7,8,9-octahydro-4H-cyclohepta[4,5]thieno[2,3-d]pyrimidin-4-one (5) or its 2-methylthio derivative 6 with hydrazonoyl chlorides 9. The mechanism of the studied reactions has been discussed and the biological activity of the isolated products has been evaluated.     

Design,synthesis, and antimicrobial activity of novel spiroisoxazolo[2,3-b][1,2,4]thiadiazole-2,2′-thiazolidine- 4′-ones and spiroisoxazolo[2,3-b][1,2,4]oxadiazole-2, 2′-thiazolidine-4′-ones

A new synthetic strategy for the synthesis of novel 6-methyl-3′-aryl spiro[isoxazolo[2,3-b][1,2,4]thiadiazole-2,2′-thiazolidin]-4′-ones (9a–9e) and 6-methyl-3′-aryl spiro[isoxazolo[2,3-b][1,2,4]oxadiazole- 2,2′-thiazolidin]-4′-ones (12a–12e) analogs is described. These compounds showed significant antimicrobial activity against all the standard strains.     

Synthesis and derivatization of angular 3-chloro-3-chlorosulfenyl naphtho[1,2-b]pyran(4H)-4-ones with evaluation of antiviral activity

Angular 2,3-dihydronaphtho[1,2-b]pyran(4H)-4-ones 1a,b react with an excess of thionyl chloride to give the α-chlorosulfenyl chlorides 2a,b, which are reduced by iodide ion to give the corresponding 1,3,4-oxadithiino derivatives 3a,b. However, the aducts 4a,b and 5a,b were obtained by reduced 2a,b with iodide ion in the presence of 2,3-dimethyl-1,3-butadiene and 1,3-cyclohexadiene, respectively. Direct oxidation of 2a,b afford 3,3-dichloronaphthopyran-4-ones 6a,b, whilst conversion to the sulfenamides 7a,b prior to oxidation provides 3-chloronaphthopyranones 8a,b. While α-chloro β-oxo sulfenyl chlorides 2a,b undergo straight forward substitution with 1-methylpiperazine and with potassium cyanide to give 9a,b and 10a,b, respectively. Some of the prepared products were selected and tested for their antiviral activity against herpes simplex virus type-1 (HSV-1). Plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with test compounds. Compound 5a showed moderate effect against HSV-1.     

2-Mercapto-4,6-disubstituted nicotinonitriles: versatile precursors for novel mono- and bis[thienopyridines]

A series of novel thieno[2,3-b]pyridines were prepared from the reaction of the appropriate bromoacetylbenzofurans or bromoacetylbenzothiazole with the corresponding pyridinethione derivatives in ethanolic sodium ethoxide at reflux. Moreover, new bis(thieno[2,3-b]pyridine) derivatives have also been synthesized by the reaction of the appropriate bis-bromoacetyl derivatives with the corresponding pyridinethiones in the presence of sodium ethoxide. Attempts to synthesize the target bis(thieno[2,3-b]pyridine) derivatives by bis-alkylation of the corresponding (thieno[2,3-b]pyridin-2-yl)(hydroxyphenyl)methanone with the appropriate dihaloalkanes using a mild base were unsuccessful.     

Reaction of hydrazonoyl halides 49 1: Synthesis and antimicrobial activity of some new pyrimido[1,2-b][1,2,4,5]tetrazin-6-one,tetrazino[3,2-b]quinazolin-5-one,pyrimidino[1,2-b]1,2,4,5-tetrazin-5-one and triazolo[4,3-a]pyrimidine derivatives

Pyrimido[1,2-b][1,2,4,5]tetrazin-6-one, tetrazino[3,2-b]quinazolin-5-one, pyrimidino[1,2-b]1,2,4,5-tetrazin-5-one and triazolo[4,3-a]pyrimidine derivatives were synthesized from C-(4-methyl-2-phenyl)thiazol-5-oyl-N-phenyl-hydrazonoyl bromide and different pyrimidine-2-thiones. New compounds had their structures confirmed by elemental and spectral analysis and were screened antimicrobial activity.     

Facile synthesis and characterization of novel bis(2-S-alkylpyridines) and bis(3-aminothieno[2,3-b]pyridines) incorporating 1,3-diarylpyrazole moiety

3-(4-Hydroxyphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (1) is condensed with acetophenone to afford the corresponding unsaturated carbonyl compound 4 whose potassium salt is reacted with 1,4-dibromobutane to afford the bis-unsaturated carbonyl compound 3. Both carbonyl compounds 3 and 4 are reacted with 2-cyanoethanethioamide, through Michael addition reaction followed by cyclocondensation, to prepare the starting materials bis(pyridine-2(1H)-thione) derivative 5 and pyridine-2(1H)-thione derivative 8. Two synthetic routes to synthesize the target materials 7 and 14 are described to get the most efficient method for preparation and maximum yield%. The first route came from the direct alkylation of the bis(pyridine-2(1H)-thione) derivative 5 using iodomethane (6a) and benzyl chloride (6b) to afford the corresponding bis(2-S-alkylpyridine) derivatives 7a,b. The reaction of 5 with halo-containing compounds 10a–d to synthesize the target materials bis(3-aminothieno[2,3-b]pyridine) derivatives 14a–d failed under various reaction conditions. The second route involves the reaction of pyridine-2(1H)-thione derivative 8 with 6a,b and 10a–d to afford the corresponding 2-S-alkylpyridine derivatives 9a,b and 3-aminothieno[2,3-b]pyridine derivatives 13a–d, through the formation of 2-S-alkylpyridine derivatives 12a–d followed by a Thrope-Ziegler reaction, whose potassium salts reacted with 1,4-dibromobutane to afford the corresponding target materials 7a,b and 14a–d, respectively. The structures of target molecules were elucidated using elemental analyses and spectral data.     

Pyrido[2,3-d]pyrimidine-2,7-dithiol in heterocyclic synthesis: Synthesis and characterization of several new fused pyridopyrimidine heterocycles

Pyridine-2(1H)-thione 1 reacted with phenyl isothiocyanate to give pyrido[2,3-d]pyrimidine derivative 3. Compound 3 reacted with halogen containing compounds 4a–d and methyl iodide in dimethylformamide/potassium hydroxide solution at room temperature to give 2,7-bisalkylthiopyrido[2,3-b]pyrimidine derivatives 5a–d and 9, respectively. Compounds 5a–d could be cyclized into thienopyrido[2,3-d]pyrimidine derivatives 6a–d by boiling with ethanolic potassium hydroxide solution. Compound 6a reacted with acetic anhydride or formic acid and gave the corresponding pyrimido[4″,5″:4′,5′]thieno[3′,2′:5,6]pyrido[2,3-d]pyrimidine derivatives 8a,b. Compound 9 reacted with hydrazine hydrate to yield pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidine derivative 11 which could be reacted with nitrous acid and dimethylformamide-dimethylacetal (DMF-DMA) and gave the final isolable products corresponding to the pyrazolo[4′,3′:5,6]pyrido[2,3-d]tetrazolo-[5,1-b]pyrimidine and pyrimido[1″,2″:1′,5′]pyrazolo[4′,3′:5,6]pyrido[2,3-d]1 Abbas, A. A., Elneairy, M. A.A. and Mabkhot, Y. N. 2001. J. Chem. Res.(S), 4: 124[Crossref] , [Google Scholar] 2 Riad, B. Y., Negem, A. M., Abdou, S. E. and Daboun, H. A. 1987. Heterocycles, 26: 205[Crossref], [Web of Science ®] , [Google Scholar] 4 Gad-Elkareem, M. A.M. and Abedelhamid, A. O. 2004. Afinidad, 61(513): 427[Web of Science ®] , [Google Scholar]triazolo-[4,3-b] pyrimidine derivatives 13 and 17, respectively. Compound 11 also reacted with some β-dicarbonyl compounds such as acetylacetone (18) and ethyl acetoacetate (20) to yield the corresponding pyrimido[1″,2″:1′,5′]pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidine derivatives 19 and 21, respectively. Finally, compound 11 reacted with chloroacetyl chloride (22) to give the corresponding imidazo[1″′,2″′:1″,5″]pyrazolo[4″,3″:5′,6′]pyrido[3′,2′:5,6]pyrimido[2,1-c]1 Abbas, A. A., Elneairy, M. A.A. and Mabkhot, Y. N. 2001. J. Chem. Res.(S), 4: 124[Crossref] , [Google Scholar] 2 Riad, B. Y., Negem, A. M., Abdou, S. E. and Daboun, H. A. 1987. Heterocycles, 26: 205[Crossref], [Web of Science ®] , [Google Scholar] 4 Gad-Elkareem, M. A.M. and Abedelhamid, A. O. 2004. Afinidad, 61(513): 427[Web of Science ®] , [Google Scholar]triazine derivative 23.     

A facile synthesis of some novel fused [1,2,4]triazolo[3,4-b][1,3,4]thiadiazol derivatives

A series of novel 3-[6-(4-substituted phenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-ylmethyl]-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one derivatives (7a–7h) have been synthesized from 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (1) through a multi-step reaction sequence. The key intermediate (6) on condensation with various substituted aromatic carboxylic acids in the presence of phosphorus oxychloride afforded the series of title compounds (7a–7h). The structures of all newly synthesized compounds were established on the basis of their IR, ¹H-NMR, ¹³C-NMR and liquid chromatography mass spectrometry spectral data.     

Synthesis of some new 3-mercapto-5-substituted-1,2,4-triazine-s-triazoles for evaluation as antimicrobial agents

The synthesis of several S- and N-substituted derivatives of 5-[(5,6-diphenyl-1,2,4-triazin-3-yl)oxymethyl]-s-triazole-3-thiol, 2-[(5,6-diphenyl-1,2,4-triazin-3-yl)-oxymethyl]-5,6-dihydrothiazolo-[3,2-b]-s-briazole, 2-[(5,6-diphenyl-1, 2,4-triazin-3-yl)oxymethyl]-5H,6,7-dihydro-s-triazolo-[3,2-b]-1,3-thiazine, 2-[(5,6-diphenyl-1,2,4-triazin-3-yl)oxymethyl]-5,6-dihydrothiazolo-[3,2-b]-s-triazol-5-one and 2-[(5,6-diphenyl-1,2,4-triazin-3-yl)oxymethyl]-6-phenylthiazolo-[3,2-b]-s-triazole is reported. All the novel compounds have been screened for antimicrobial activity and one of them showed noteworthy activity.     

Regioselective synthesis and pharmacological activities of spirodibenzo[a,d]cycloheptene-5,2′-[1,3,4]thiadiazole derivatives

Some new 3^′,5^′-substituted-5H,3^′ H-spirodibenzo[a, d]cycloheptene-5,2^′-[1,3,4]thiadiazole and 10,11-dihydro-5H,3^′ H-spirodibenzo[a, d]cycloheptene-5,2^′-[1,3,4]thiadiazole derivatives 3a–n were regioselectively synthesized under 1,3-dipolar cycloaddition of 5-thiooxo-5H-dibenzo[a, d]cyclo-heptene and 5-thiooxo-10,11-dihydro-5H-dibenzo[a, d]cycloheptene with a variety of nitrilimines (generated in situ via dehydrohalogenation of the corresponding hydrazonoyl chlorides in the presence of triethylamine). The new products were tested for antiinflammatory, analgesic, and ulcerogenic score activities comparable to Indomethacin. Compounds 3i–l showed significant activity compared to Indomethacin.     

Reaction of pyridothiouracil with hydrazonoyl halides and the antimicrobial activity of the products,pyrido[2,3-d][1,2,4]triazolo-[4,3-a]pyrimidin-5(1H)-one derivatives

New functionalized pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-one derivatives were synthesized via reaction of the hydrazonoyl halides with 7-(4-nitrophenyl)-5-phenyl-2,3-dihydro-2-thioxopyrido[2,3-d]pyrimidin-4(1H)-one or its 2-methylthio derivative. The biological activity of the products has been evaluated. The mechanism and the regioselectivity of the studied reactions have been discussed.     

Regioselective synthesis of indole-annulated sulfur heterocycles by tri-n-butyltin hydride-mediated aryl radical cyclization

2-[(2-Bromobenzyl)sulfonyl]indoles under Bu₃SnH-mediated aryl radical cyclization furnished exclusively the benzo[c]thiopyrano[2,3-b]indoles in 56–61% yields via 6-endo-trig cyclization whereas 2-[(2-bromobenzyl)sulfanyl]indole 3a gave only the β-scission product.     

Regioselective synthesis of new 5H,10H-dipyrimido[2,1-b:4′,5′-d][1,3]thiazine: a combined experimental and computational study

Several derivatives of the novel tricyclic system ‘dipyrimido[2,1-b:4′,5′-d][1,3]thiazine’ were synthesized via inter- and intramolecular heterocyclization of 2,4-dichloro-5-(chloromethyl)-6-methylpyrimidine and 6-amino-4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile in short reaction times under mild conditions. An x-ray analysis together with computational calculations was performed to gain an in-depth understanding of regioselectivity of the reaction.     

A simple green synthesis of (Z)-5-arylmethylene-4- thioxothiazolidines and thiopyrano[2,3-d]thiazolidine-2-thiones in PEG-400 under catalyst-free conditions

An improved Knoevenagel condensation of various aromatic aldehydes with thiazolidine-2,4-dithione and with 4-thioxothiazolidin-4-one can be achieved at room temperature in polyethylene glycol-400 without catalyst to afford (Z)-5-arylmethylene-4-thioxothiazolidine derivatives 3a–3o. Also, the [4+2] cyloaddition reaction of 3a–3g with N-phenylmaleimide 4 gave the cycloadducts 5a–5g under the same reactions conditions. The structure of all the newly synthesized compounds was established on the basis of the elemental analysis and spectral data. This process is a simple, efficient, economical, and environmentally benign compared to classical reactions.     

A short-cut to 2,7-dihydrothiopyrano[2,3-b]pyrrole

A simple original approach to earlier unknown parent 2,7-dihydrothiopyrano[2,3-b]pyrrole (5) from allyl isothiocyanate and propargyl bromide via one-pot synthesis and thermal rearrangement of 2-(prop-2-ynylsulfanyl)-1H-pyrrole (4) has been developed. The compound 5 in the present study was successfully examined as 2,7-dihydrothiopyrano[2,3-b]pyrrole scaffold in the synthesis of corresponding N- and C-pyrrolecarbodithioates.     

Synthesis and antimicrobial activities of some ethyl 2-arylthio-6-arylimidazo[2,1-b]thiazole-3-carboxylates and their sulfones

A series of new 2-arylthio-3-ethoxycarbonyl-6-arylimidazo[2,1-b]thiazoles (4a–4h) and 2-arenesulfonyl-3-ethoxycarbonyl-6-arylimidazo[2,1-b]thiazoles (5a–5h) have been prepared and characterized by analytical and spectral methods. The title compounds 4a–4h and 5a–5h were obtained by the reaction of 2-amino-4-ethoxycarbonyl-5-arylthiothiazoles (2a and 2b)/2-amino-4-ethoxycarbonyl-5-arenesulphonyl-thiazoles (3a and 3b) with various phenacyl bromides in anhydrous ethanol. These newly synthesized compounds (4a–4h and 5a–5h) were screened for their antibacterial activity against Gram-negative bacterium Escherichia coli, Gram-positive bacterium Staphylococcus aureus, and antifungal properties against Aspergillus niger and Candida albicans.     

The electrocatalytic cascade assembling of isatins, malononitrile and N-alkyl barbiturates: An efficient multicomponent approach to the spiro[indole-3,5′-pyrano[2,3-d]pyrimidine] framework

Electrochemically induced catalytic multicomponent transformation of isatins, barbituric acid or N-alkyl barbiturates and malononitrile in alcohols in an undivided cell results in the formation of substituted 7′-amino-2,2′,4′-trioxo-1,1′,2,2′,3′,4′-hexahydrospiro[indole-3,5′-pyrano[2,3-d]pyrimidine]-6′-carbonitriles in 80–95% yields. The developed efficient electrocatalytic approach to corresponding spiro[indole-3,5′-pyrano[2,3-d]pyrimidine] system is beneficial from the viewpoint of diversity-oriented large-scale processes and represents a new example of the ecologically pure synthetic concept for electrocatalytic multicomponent reactions strategy.