Cyanoacetanilides Intermediates in Heterocyclic Synthesis. Part 5: Preparation of Hitherto Unknown 5‐Aminopyrazole and Pyrazolo[1,5‐a]pyrimidine Derivatives Containing Sulfamoyl Moiety

Novel 5‐aminopyrazole and pyrazolo[1,5‐a]pyrimidine derivatives have been synthesized from the readily accessible cyanoacetanilide derivative ( 2 ).     

Cyanoacetanilides Intermediates in Heterocyclic Synthesis,Part 3: Novel Syntheses of Thiazolinone and Thiazolo[3,2-a]Pyridine Derivatives

Thiazolo[3,2-a]pyridines 6a–c , 10 , 13 , and 14 have been synthesized via simple methods from the readily accessible 2-[N-(4-ethoxyphenyl)-acetamide-2-yl]-4,5-dihydro-4-thiazolinone 2. The structure of the synthesized compounds was established by analytical and spectral data.     

Heterocyclic Synthesis with Nitriles: Synthesis of Pyrazolopyrimidine and Pyrazolopyridine Derivatives

The reaction of N ₁-substituted-5-amino-4-cyanopyrazoles with malononitrile and diethylmalonate occurs with formation of 6-substituted pyrazolo[3,4-d]pyrimidines, and pyrazolo[3,4-b]pyridines respectively. The structures of the products and conceivable mechanisms are discussed.     

Cyanoacetamide Intermediate in Heterocyclic Synthesis: Synthesis and Biological Evaluation of Hitherto New Dioxoisoindoline Heterocyclic Derivatives

Innovative poly‐substituted heterocyclic rings incorporating dioxoisoindoline ( 2 – 25 ) were synthesized through the reaction of dioxoisoindoline derivative 2 as starting compound with various types of reagents. All compounds were characterized by appropriate means of (¹H‐NMR, ¹³C‐NMR, IR, and mass). The prepared compounds were evaluated as antimicrobial agents against Escherichia coli, Staphylococcus aureus, and Candida albicans microorganisms. The tested compounds exhibited low to moderate antibacterial activities and promising results as antifungal agents.     

Studies on Thiazolopyridines. Part 4: Synthesis of Hitherto Unknown 1,4-Bis(thiazolopyridine)benzene Derivatives

2-Cyanomethyl-4-thiazolinone ( 1 ) was condensed with terephthalaldehyde ( 2 ) (2:1 molar ratio) and produced 1,4-bis(2-cyanomethyl-4,5-dihydro-5-methylidene-4-thiazolinone-5-yl) benzene ( 3 ). Treatment of compound ( 3 ) with benzylidenemalononitrile ( 4 ) (1:2 molar ratio) furnished the novel bisthiazolopyridines ( 6a-e ). Condensation of compound ( 1 ) with aromatic aldehyde yielded the benzylidene derivatives ( 7a-f ), which on treatment with compound ( 8 ) (2:1 molar ratio) afforded the novel bisthiazolopyridines ( 10a-f ). Structures of the synthesized compounds have been established by elemental analyses and spectral data.     

Heterocyclic Synthesis Using Nitrilimines:Part 16. Synthesis of Some New Pyrazole and Spiropyrazoline Derivatives

1,3‐Dipolar cycloaddition of the nitrilimines with the 2‐propylidene‐3‐coumaranone afforded the corresponding pyrazole derivatives. Similar reactions of nitrilimines with 3‐ethylidene‐1‐indanone furnished spiropyrazoline derivatives. The spectral data of the synthesized compounds are in full agreement with its molecular structure.     

Pyrazolones as Building Blocks in Heterocyclic Synthesis: Synthesis of New Pyrazolopyran,Pyrazolopyridazine and Pyrazole Derivatives of Expected Antifungicidal Activity

A series of new pyrazolone and pyrazole derivatives with expected antifungicidal activity have been prepared through the reactions 3‐phenyl‐1‐H‐pyrazol‐5(4H)‐one ( 3 ) and 4‐(dimethylaminomethylene)‐3‐phenyl‐1H‐pyrazol‐5(4H)‐one ( 5 ) with a variety of electrophilic reagents and nucleophilic reagents. The newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR and mass spectral studies.     

Cyanothioacetanilide Intermediates in Heterocyclic Synthesis,Part 1: Synthesis and Biological Evaluation of Some Novel Thiazole,Thiophene, Pyrazole,and Pyrazolo[1,5-a]Pyrimidine Derivatives

Some novel thiophenes (4a,b, 5, and 9a,b) were obtained from the cycloalkylation of the thiocarbamoyl group in the cyanothioacetanilide derivative (1) with α-halocarbonyl compounds. Also, the reaction of cyanothioacetanilide derivative with phenyl isothiocyanate in the presence of potassium hydroxide followed by in situ heterocyclization of the resulting adduct with α-halocarbonyl compounds furnished the corresponding thiazole (12, 14, and 15), pyrazole (19), and pyraozlo[1,5-a]pyrimidine (22, 25, and 26) derivatives. Compounds (4b, 5, 9a, 12, 13, 18, 22, 25, and 26) were tested to evaluate their antimicrobial activity.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

β‐Enaminonitriles in Heterocyclic Synthesis: Synthesis of New 1,4‐Dihydropyridine,Tetrahydropyridine, Nicotinonitrile and Aminopyrazole Derivatives

A series of new pyridine, dihydropyridine, tetrahydropyridine, nicotinonitrile and pyrazole derivatives with expected biological activity were prepared through the reactions of 3‐aminopent‐2‐enenitrile 1 with some electrophilic reagents, nucleophilic reagents, and aryl diazonium salts. The newly synthesized compounds were characterized by IR, ¹H‐NMR, ¹³C‐NMR and mass spectral studies.     

Dapson in Heterocyclic Chemistry,Part I: Novel Synthesis of Sulfone Biscompounds for Antimicrobial and Antitumor Activities

This article describes the synthesis of some novel sulfone bis-compounds bearing the biologically active thioether 3–6 ; thioureido 7, 8, 15, 16; triazole 10, 11; thiosemicarbazido 9, 12, 13; and 1,3,4-thiadiazole 14, 17 moieties starting with 4,4′-diisothiocyanato-1,1-diphenylsulfone 2. The structures of newly synthesized compounds were confirmed by elemental analysis, IR, ¹ H-NMR and mass spectral data. Compound 3 was found to be the most active compound against Escherichia coli. Also, compound 15 acted as potent cytotoxic agent.     

Synthesis and Characterization of Some New Benzimidazole Derivatives

Synthesis of nine new benzimidazole derivatives was reported. The products were identified by ¹H NMR, mass spectroscopy, and infrared spectroscopy.     

Acetoacetanilides in Heterocyclic Synthesis,Part 1: An Expeditious Synthesis of Thienopyridines and Other Fused Derivatives

3-Oxo-N-{4-[(pyrimidin-2-ylamino)sulfonyl]phenyl}butanamide 1 reacts with arylidinecyanothioacetamide in refluxing ethanolic TEA to give the pyridinethione 2 rather than thiopyrane 4. Compound 2 reacts with α-haloketones to give the s-alkylated derivatives 7a–e. Compound 7a–e undergoes cyclization into thieno[2,3-b]pyridine derivatives 8a–e. The saponification of 8a gives the amino acid 9, which affords 10 when refluxed in Ac₂O. The treatment of 10 with NH₄OAc/AcOH gives 11. Compound II is also obtained when 8e is refluxed in Ac₂O. The reaction of 8a with hydrazine hydrate gives 12 and with formamide gives 13. Compound 13 also is obtained from the reaction of 8e with triethylorthoformate. The acetylation of 8a with Ac₂O gives the amide derivative 14, which, on treatment with aromatic amines, affords 15a–c. Compounds 15a–c are cyclized with H₂SO₄ to 16a–c. Compound 16 is obtained also from the acetylation of compound 8c, d by Ac₂O. Reactions of compound 8e with CS₂ in refluxing dioxane afford 17. The diazotization and self-coupling of 8e give the pyridothienotriazine 18. Finally, the chloronation of compound 13 with POCl₃ affords the chloride derivative 19.     

Utility of Enaminonitriles in Heterocyclic Synthesis: Synthesis of Some New Pyrazole,Pyridine, and Pyrimidine Derivatives

The starting (1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)carbonohydrazonoyl dicyanide ( 2 ) was used as key intermediate for the synthesis of 3‐amino‐2‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐ylazo)‐[3‐substituted]‐1‐yl‐acrylonitrile derivatives ( 3 – 10 ). In addition, nitrile derivative 2 reacted with hydrazine hydrate or malononitrile to afford the corresponding 3,5‐diaminopyrazole 11 and enaminonitrile derivative 13 , respectively. On the other hand, compound 3 was subjected to react with malononitrile, acetic anhydride, triethylorthoformate, N,N‐dimethylformamide (DMF)‐dimethylacetal, thiourea, and hydroxylamine hydrchloride to afford antipyrine derivatives 16 – 21 . Moreover, the reaction of enaminonitrile 3 with carbon disulfide in pyridine afforded the pyrimidine derivative 22 , whereas, in NaOH/DMF followed by the addition of dimethyl sulphate afforded methyl carbonodithioate 24 . The reaction of enaminonitrile derivatives 3 – 5 with phenylisothiocyanate afforded the thiopyrimidine derivatives 25a – c . Finally, the enaminonitrile 4 reacted with 3‐(4‐chloro‐phenyl)‐1‐phenyl‐propenone to afford the pyridine derivative 27 . The newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹³C‐NMR, ¹H–NMR, and MS).     

Utility of Enaminonitriles in Heterocyclic Synthesis: Synthesis of Some New Azepine,Azocine, and Pyrroldione Derivatives

Reactions of enaminonitrile derivative 3 with a variety of reagents lead to the syntheses of novel 1,2,4‐triazepin 7 , 1,4‐thiazepinone 9 , oxazocines 13 , 14 , oxadiazocines 15 , 16 , and pyrroldiones 17 , 18 , 19 , 20 , 21 22 with the aim to explore the use of this exceptionally reactive enaminonitrile 3 in heterocyclic synthesis. Newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹H‐NMR, ¹³C‐NMR, and MS).