A structural study of 4‐aminoantipyrine and six of its Schiff base derivatives

Six derivatives of 4‐amino‐1,5‐dimethyl‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐3‐one (4‐aminoantipyrine), C₁₁H₁₃N₃O, (I), have been synthesized and structurally characterized to investigate the changes in the observed hydrogen‐bonding motifs compared to the original 4‐aminoantipyrine. The derivatives were synthesized from the reactions of 4‐aminoantipyrine with various aldehyde‐, ketone‐ and ester‐containing molecules, producing (Z)‐methyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]but‐2‐enoate, C₁₆H₁₉N₃O₃, (II), (Z)‐ethyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]but‐2‐enoate, C₁₇H₂₁N₃O₃, (III), ethyl 2‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]cyclohex‐1‐enecarboxylate, C₂₀H₂₅N₃O₃, (IV), (Z)‐ethyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]‐3‐phenylacrylate, C₂₂H₂₃N₃O₃, (V), 2‐cyano‐N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)acetamide, C₁₄H₁₄N₄O₂, (VI), and (E)‐methyl 4‐{[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]methyl}benzoate, C₂₀H₁₉N₃O₃, (VII). The asymmetric units of all these compounds have one molecule on a general position. The hydrogen bonding in (I) forms chains of molecules via intermolecular N—H...O hydrogen bonds around a crystallographic sixfold screw axis. In contrast, the formation of enamines for all derived compounds except (VII) favours the formation of a six‐membered intramolecular N—H...O hydrogen‐bonded ring in (II)–(V) and an intermolecular N—H...O hydrogen bond in (VI), whereas there is an intramolecular C—H...O hydrogen bond in the structure of imine (VII). All the reported compounds, except for (II), feature π–π interactions, while C—H...π interactions are observed in (II), C—H...O interactions are observed in (I), (III), (V) and (VI), and a C—O...π interaction is observed in (II).     

A convenient route to pyridones,pyrazolo[2,3‐a]pyrimidines and pyrazolo[5,1‐c]triazines incorporating antipyrine moiety

Condensation of 4‐aminoantipyrine with ethyl acetoacetate, ethyl benzoylacetate, and ethyl cyanoacetate furnished the corresponding ethyl 3‐(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)aminoacrylate and 2‐cyano‐N‐[(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)]acetamide derivatives. The aminoacrylates derivatives react with acetonitrile and sodium hydride to give 2‐amino‐6‐methyl‐1‐(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)‐4‐pyridone. Reaction of the cyanoacetamide derivative with dimethylformamide‐dimethylacetal (DMF‐DMA) afforded 2‐cyano‐N‐[1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐pyrazol‐4‐yl]‐2‐(N,N‐dimethylamino)methylene acetamide in high yield. Treatment of the latter with 5‐aminopyrazole derivatives afforded the corresponding pyrazolo[2,3‐a]pyrimidines. 2‐cyano‐N‐[(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)]acetamide also reacts with heterocyclic diazonium salts to give the corresponding pyrazolo[5,1‐c]‐1,2,4‐triazine derivatives. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:508–514, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20046     

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).     

Facile Synthesis of Pyrazolo[3,4‐c]pyrazoles Bearing Coumarine Ring as Anticancer Agents

In the present study, 2‐(2‐oxo‐2H‐chromene‐3‐carbonyl)‐5‐phenyl‐2,4‐dihydro‐3H‐pyrazol‐3‐one was prepared and reacted with various hydrazonoyl halides to give a series of 2‐(2‐oxo‐2H‐chromene‐3‐carbonyl)‐5‐phenyl‐4‐((2‐phenylhydrazono)methyl)‐2,4‐dihydro‐3H‐pyrazol‐3‐one in good yield. Cyclization of the latter hydrazone with POCl₃ yielded the respective 3‐(3‐phenyl‐ 4,6‐disubstituted‐1,6‐dihydropyrazolo[3,4‐c]pyrazole‐1‐carbonyl)‐2H‐chromen‐2‐ones. The structures of the newly synthesized compounds were established on the basis of spectroscopic evidences and their alternative syntheses. The newly synthesized compounds were evaluated for their antitumor activities against hepatocellular carcinoma (HepG2) cell line and the results revealed promising activities of compounds 4e , 4c , and 4d with IC₅₀ equal 0.92 ± 0.22, 1.43 ± 0.19, and 2.17 ± 0.21 μM, respectively.     

Synthesis of Some Heterocyclic Compounds from 1H‐Indole‐2,3‐Dione: A Direct One‐Pot Synthesis of Spiro Indolone Derivatives

Some spiro indolone derivatives 5_a,b and 6 were synthesized through one‐pot synthesis via the ternary condensation of 1H‐indole‐2,3‐dione 1 , 3‐methyl‐1‐phenyl‐2‐pyrazolin‐5‐one 2 and active methylenes, namely malononitrile, ethyl cyanoacetate 4_a,b and pyrazolone 2 , respectively. The same derivatives can be obtained via other methods, through reactions of 3‐[3‐methyl‐5‐oxo‐1‐phenyl‐1,5‐dihydro‐pyrazol‐(4Z)‐ylidene]‐1,3‐dihydro‐indol‐2‐one 3 with the corresponding active methylenes. Reaction of 3 with amines and with ethyl vinyl ether was studied.     

A Novel Diastereoselective Synthesis of 6‐Aryl‐5‐hydroxy‐2,3‐dihydropyrano[2,3‐c]pyrazol‐4(1H)‐ones

A novel one‐pot diastereoselective synthesis of trans‐6‐aryl‐5‐hydroxy‐2,3‐dihydro[2,3‐c]pyrazol‐4(1H)‐ones 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h is described via the Darzens condensation reaction of 2‐chloro‐1‐(5‐hydroxy‐3‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)ethanone ( 2 ) with different aromatic aldehydes in aqueous basic medium. The structures of the compounds prepared were determined by analytical and spectral analyses.     

Pyridine‐2(1H)‐thiones: Versatile Precursors for Novel Pyrazolo[3,4‐b]pyridine,Thieno[2,3‐b]pyridines,and Their Fused Azines

Pyridine‐2(1H)‐thiones were prepared and reacted with several active halogenated reagents to afford novel thieno[2,3‐b]pyridines in excellent yields. Thieno[2,3‐b]pyridine‐2‐carbohydrazide derivative was prepared by the reaction of either ethyl 2‐((3‐cyanopyridin‐2‐yl)thio)acetate derivative or thieno[2,3‐b]pyridine‐2‐carboxylate derivative with hydrazine hydrate. On the other hand, the reaction of either pyridine‐2(1H)‐thione or ethyl 2‐((pyridin‐2‐yl)thio)acetate derivative with hydrazine hydrate afforded the corresponding 1H‐pyrazolo[3,4‐b]pyridine derivative. Thieno[2,3‐b]pyridine derivatives reacted with several reagents to afford the corresponding pyrimidine‐4(3H)‐ones and [1,2,3]triazin‐4‐(3H)‐one. Moreover, 2‐carbohydrazide derivative reacted with β‐dicarbonyl reagents to give 2‐((3‐methyl‐1H‐pyrazol‐1‐yl)carbonyl)thienopyridines. The structure of the target molecules is elucidated using elemental analyses and spectral data.     

Conventional and Microwave‐Assisted Synthesis and Biological Activity Study of Novel Heterocycles Containing Pyran Moiety

Under both conventional and microwave methods, 2‐amino‐4H‐pyran‐3‐carbonitrile derivative 1 was synthesized and reacted with different reagents. Thus, 2‐amino‐4H‐pyran‐3‐carbonitrile derivative was treated with chloroacetyl chloride, phenyl isocyanate, cyanoacetic acid, benzoyl chloride, triethyl orthoformate, acetic anhydride/H₂SO₄, arylidene malononitrile, urea, and/or p‐aminosulphaguanidine producing chloroacetamide, 3‐phenylurea, cyanoacetamide, N‐benzoylpyran, ethylformimidate, pyranopyrimidin‐4‐one, pyranopyridine, pyranopyrimidin‐2‐one, and pyranopyrimidin‐2‐imine derivatives, respectively. Meanwhile, compound 1 was reacted with ethyl bromoacetate, phenacyl bromide, phthalic anhydride, different aromatic amines, and/or acetic acid/H₂SO₄ to produce 5‐aminopyrano[2,3‐b]pyrrole‐6‐carboxylate, dihydropyrano[2,3‐b]pyrrole‐6‐yl‐(phenyl)methanone, 1,3‐dioxoisoindolinyl pyran, 1,4‐dihydropyridine, and 2‐hydroxy‐1,4‐dihydropyridine derivatives, respectively. On the other hand, when compound 1 was allowed to react with maleic anhydride and/or hydrazine hydrate, pyran‐4‐oxobut‐2‐enoic acid and 3‐aminopyranopyrazole derivatives were obtained, respectively. Reaction of pyran‐4‐oxobut‐2‐enoic acid with malononitrile under different conditions gave 2‐(furan‐2‐yl)‐4H‐pyran and 2‐(4H‐pyran‐2‐yl)‐1H‐pyrrole derivatives, while condensation of 3‐aminopyranopyrazole with benzaldehyde gave 1,4‐dihydropyrano[2,3‐c]pyrazol‐3‐yl‐1‐phenylmethanimine derivative. The newly synthesized compounds were characterized by the spectroscopic tools IR, ¹H‐NMR, ¹³C‐NMR, MS, and elemental analysis. Some of these compounds have been screened in vitro for antimicrobial activity against different strains of bacteria and fungi and also were tested against two cancer cell lines: mammary gland breast cancer (MCF‐7) and colon cancer (HCT‐118).     

Different molecular conformations co‐exist in each of three 2‐aryl‐N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)acetamides: hydrogen bonding in zero,one and two dimensions

4‐Antipyrine [4‐amino‐1,5‐dimethyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐one] and its derivatives exhibit a range of biological activities, including analgesic, antibacterial and anti‐inflammatory, and new examples are always of potential interest and value. 2‐(4‐Chlorophenyl)‐N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)acetamide, C₁₉H₁₈ClN₃O₂, (I), crystallizes with Z′ = 2 in the space group P, whereas its positional isomer 2‐(2‐chlorophenyl)‐N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)acetamide, (II), crystallizes with Z′ = 1 in the space group C2/c; the molecules of (II) are disordered over two sets of atomic sites having occupancies of 0.6020 (18) and 0.3980 (18). The two independent molecules of (I) adopt different molecular conformations, as do the two disorder components in (II), where the 2‐chlorophenyl substituents adopt different orientations. The molecules of (I) are linked by a combination of N—H…O and C—H…O hydrogen bonds to form centrosymmetric four‐molecule aggregates, while those of (II) are linked by the same types of hydrogen bonds forming sheets. The related compound N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)‐2‐(3‐methoxyphenyl)acetamide, C₂₀H₂₁N₃O₃, (III), is isomorphous with (I) but not strictly isostructural; again the two independent molecules adopt different molecular conformations, and the molecules are linked by N—H…O and C—H…O hydrogen bonds to form ribbons. Comparisons are made with some related structures, indicating that a hydrogen‐bonded R₂²(10) ring is the common structural motif.     

Synthesis of new thienotriazolopyrimidine and thienopyrimidotetrazine derivatives from bifunctional intermediates

New compounds containing the thienotriazolopyrimidine and thienopyrimidotetrazine skeleton are prepared from the bifunctional intermediates 2,3‐diamino‐5,6‐dimethylthieno[2,3‐d]pyrimidin‐4(3H)‐one derivatives 13–17 . The 2,3‐dihydro‐3‐substituted‐5,6‐dimethylthieno[2,3‐d]pyrimidin‐4(1H)‐one derivatives 8–12 are also prepared.     

Attempted synthesis of ethyl 3,4‐dihydro‐2H‐1,4‐benzoxazine‐3‐carboxylate and 3‐acetate derivatives

Ethyl 3,4‐dihydro‐2H‐1,4‐benzoxazine‐3‐carboxylate derivatives 2 were obtained and isolated in low yields from the condensation of 2‐aminophenol and ethyl 2,3‐dibromopropanoate. They can be obtained by hydrogenation of ethyl 2H‐1,4‐benzoxazine‐3‐carboxylate in satisfactory yield. Using 2‐iminophenol did not direct the condensation with ethyl 2,3‐dibromopropanoate towards 2 but was fruitfull for the preparation of ethyl 2‐(4‐benzyl‐3,4‐dihydro‐2H‐1,4‐benzoxazin‐3‐yl)acetate from ethyl bromocrotonate.     

Synthesis and Characterization of New Heterocyclic Compounds Containing Thienylbenzo[h]Quinoline Moiety

In this paper the reaction of 2‐(2′‐thienylmethylene)‐3,4‐dihydronaphthalen‐2(1H)‐one ( 1 ) with cyanothioacetamide gave a mixture of 3‐cyano‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]quinolin‐2(1H)‐thione ( 2 ) and the related disulfide 3 . Compound 2 was reacted with some halo compounds namely; ethyl chloroacetate, chloroacetamide, chloro(N‐(p‐chlorophenyl))acetamide, N¹‐chloroacetylsulfanilamide, and 2‐chloromethyl‐1H‐benzimidazole to produce a series of 2‐(substituted)methylthio‐3‐cyano‐5,6‐dihydro‐4‐(2′‐thienyl)benzo[h]quinolines 4a , 4b , 4c , 4d , 4e and 11 . Upon heating the latter compounds with sodium ethoxide, they underwent intramolecular Thorpe–Zeigler cyclization to furnish the corresponding 2‐(substituted)‐3‐amino‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]thieno[2,3‐b]quinolines 5a , 5b , 5c , 5d , 5e and 12 . (3‐Cyano‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]quinolin‐2‐ylthio)acethydrazide ( 8 ) and the related isomer, 3‐amino‐5,6‐dihydro‐4‐(2′‐thienyl)thieno[2,3‐b]benzo[h]quinoline‐2‐carbohydrazide ( 9 ), were also synthesized. Most of the aforementioned compounds were used as key intermediates for synthesizing other benzo[h]quinolines, benzo[h]thieno[2,3‐b]quinolines as well as benzo[h]pyrimido[4′,5′:4,5] thieno[2,3‐b]quinolines. The structure of all synthesized compounds was confirmed by spectroscopic measurements and analytical analyses.     

Synthesis of Functionalized H‐[1]Benzopyrano[2,3‐b]pyridines by the Friedländer Approach: Antimycobacterial and Antimicrobial Profile

A series of functionalized H‐[1]benzopyrano[2,3‐b]pyridine derivatives were synthesized by the Friedländer reaction of 2‐amino‐4‐oxo‐4H‐chromene‐3‐carbonitriles 1 with malononitrile, ethyl cyanoacetate, or acetophenone (Scheme). The synthesized compounds 2 – 4 were screened for their in vitro activity against antitubercular, antibacterial, and antifungal species (Fig., Table). Among the synthesized compounds, 3c and 4f were the most active with 99% inhibition against Mycobacterium tuberculosis H₃₇Rv, while compounds 2f, 3f , and 4d exhibited 69%, 63%, and 61% inhibition, respectively. The 4‐amino‐7,9‐dibromo‐1,5‐dihydro‐2,5‐dioxo‐2H‐chromeno[2,3‐b]pyridine‐3‐carbonitrile ( 3b ) showed the most potent antibacterial activity against Escherichia coli and Pseudomonas aeruginosa. Several chromeno[2,3‐b]pyridine derivatives showed equal or more potency against Staphylococcus aureus and Candida albicans.     

Reduction of 3‐Aminoquinoline‐2,4(1H,3H)‐diones and Deamination of the Reaction Products

3‐Aminoquinoline‐2,4‐diones were stereoselectively reduced with NaBH₄ to give cis‐3‐amino‐3,4‐dihydro‐4‐hydroxyquinolin‐2(1H)‐ones. Using triphosgene (=bis(trichloromethyl) carbonate), these compounds were converted to 3,3a‐dihydrooxazolo[4,5‐c]quinoline‐2,4(5H,9bH)‐diones. The deamination of the reduction products using HNO₂ afforded mixtures of several compounds, from which 3‐alkyl/aryl‐2,3‐dihydro‐1H‐indol‐2‐ones and their 3‐hydroxy and 3‐nitro derivatives were isolated as the products of the molecular rearrangement.     

Synthesis of Some New Polyfunctionalized Pyridines

5‐Methyl‐2,4‐dihydro‐3H‐pyrazol‐3‐one and/or 5‐methyl‐2‐phenyl‐2,4‐dihydro‐3H‐pyrazol‐3‐one was reacted with arylidenemalononitrile in the presence of sodium alkoxide to give 2‐amino‐6‐alkoxy‐4‐arylpyridine‐3,5‐dicarbonitrile 4a–e instead of the reported pyrazolo[3,4‐b]pyridine‐5‐carbonitriles. The same products 4a–e were prepared via reaction of arylidenemalononitrile with sodium alkoxide in an appropriative alcohol. However, the new synthetic route for preparation of their positional isomer 4‐amino‐6‐alkoxy‐2‐arylpyridine‐3,5‐dicarbonitrile 7a–j has been achieved via reaction of 2‐aminoprop‐1‐ene‐1,1,3‐tricarbonitrile with different aromatic aldehydes under the same conditions.     

Synthesis and properties of new macrocyclic compounds: Utilization of bond character of hypervalent sulfur in tetraazathiapentalene derivatives

2,3‐Bis[(p‐isothiocyanatomethylphenyl)methyl]‐6,7‐dihydro‐5H‐2a‐thia(2a‐S_IV)‐2,3,4a,7a‐tetraaza‐cyclopent[cd]indene‐1,4(2H,3H)‐dithione ( 3 ), prepared by the reaction of 2,3‐dimethyl‐6,7‐dihydro‐5H‐2a‐thia(2a‐S^IV)‐2,3,4a,7a‐tetraazacyclopent‐[cd]indene‐1,4(2H,3H)‐dithione ( 1 ) with p‐xylylene diisothio‐cyanate, reacted with N,N′‐dialkyl substituted diamines to give macrocyclic compounds bearing hypervalent sulfur by a ring closure reaction in good yields. These macrocyclic compounds were converted into ring‐expanded macrocyclic compounds with release of the hypervalent sulfur by treating with NaBH₄ and CF₃COOH.     

Synthesis,Antioxidant, Antituomer Activities of Some New Thiazolopyrimidines,Pyrrolothiazolopyrimidines and Triazolopyrrolothiazolopyrimidines Derivatives

Reaction of 6‐amino‐2‐thiouracil 1 with ethyl bromoacetate yielded ethyl 2‐(7‐amino‐2,5‐dioxo‐3,5‐dihydro‐2H‐thiazolo[3,2‐a]pyrimidin‐6‐yl)acetate 2 . Reaction of 2 with sodium ethoxide afforded the pyrrolothiazolopyrimidine derivative 3 . Compound 2 reacted with hydrazine hydrate to give 7‐amino‐thiazolopyrimidine‐carbohydrazide 4 . The latter compound 4 reacted with carbon disulphide to form 7‐amino‐6‐(oxadiazolylmethyl) thiazolopyrimidine 5 . Compound 5 was heated in methanol to yield 9‐thioxotriazolopyrrolothiazolopyrimidine 6 . Also, the reaction of 3 with aromatic aldehydes afforded the diarylmethylenepyrrolothiazolopyrimidine derivatives 7a‐c . The latter compounds 7a‐c underwent cyclocondensation with hydroxylamine to give diaryldioxazolopyrrolothiazolopyrimidine derivatives 8a‐c . The new prepared compounds were subjected for antioxidant and antituomer studies, some of these compounds exhibited promising activity.     

Synthesis of New Pyrrolo Heterocycles (I): Novel Synthesis of Pyrano[2,3‐c]pyrrole,Isoindoline, Pyrrolo[3,4‐b]pyridine,and Pyrrolo[3,4‐d]pyrimidine Derivatives

Michael addition of 1,5‐diaryl‐2,3‐dioxopyrrolidine derivatives with α‐cyanocinnamonitriles and ethyl α‐cyanocinnamates afforded 4H‐pyrano[2,3‐c]pyrrole derivatives in the presence of sodium ethoxide. Under the same reaction condition, the ylidenes of 1,5‐diaryl‐2,3‐dioxopyrrolidine were reacted with malononitrile or ethyl cyanoacetate to give isoindole derivatives; however, pyrrolo[3,4‐b]pyridine derivatives were formed when cyanoacetamide was used. Moreover, pyrrolo[3,4‐d]pyrimidine derivatives were synthesized by treating 4‐benzylidene‐1,5‐diphenyl‐2,3‐dioxopyrrolidine with urea and/or thiourea under basic conditions. The structures of all the new synthesized compounds were confirmed by elemental analysis, IR and NMR spectra.     

Sydnones as Masked Hydrazines for the Synthesis of 4‐Arylazo‐1,2‐dihydro‐pyrazol‐3‐one Derivatives

A simple and convenient one‐pot synthesis of 4‐(4‐chlorophenylazo)‐5‐methyl‐2‐aryl‐1,2‐dihydro‐pyrazol‐3‐ones (4a–j) has been carried out from 3‐arylsydnones (3a–j) by reaction with 2‐(4‐chlorophenyl)‐hydrazono‐3‐oxo‐butyric acid ethyl ester (2b). The 3‐arylsydnones are used as masked hydrazines in this reaction. Similarly, the 4‐arylazo‐2‐(7‐hydroxy‐4‐methyl‐2‐oxo‐2H‐chromen‐8‐ylmethyl)‐5‐methyl‐1,2‐dihydro‐pyrazol‐3‐ones (7a–j) were synthesized from 3‐[(7‐acetoxy‐4‐methyl‐8‐methylene)coumaryl]sydnone (5). All the newly synthesized compounds exhibited antimicrobial activity greater than the reference drugs used.     

Syntheses,Characterization, and Antibacterial Activities of Four New Schiff Base Compounds Derived from 1‐Phenyl‐3‐methyl‐4‐benzoyl‐2‐pyrazolin‐5‐one

Four new Schiff bases were designed and synthesized. 5‐Methyl‐4‐(4‐aminophenylamino‐phenyl‐methylene)‐2‐phenyl‐2,4‐dihydro‐pyrazol‐3‐one (compound 1 ) and 5‐methyl‐4‐(2‐aminophenylamino‐phenyl‐methylene)‐2‐phenyl‐2,4‐dihydro‐pyrazol‐3‐one (compound 2 ) were synthesized by interaction of 1‐phenyl‐3‐methyl‐4‐benzoyl‐2‐pyrazolin‐5‐one (PMBP) with o‐ and p‐phenylenediamine, respectively; 4,4′‐(1,2‐phenylenebis(azanediyl)bis(phenylmethanylylidene))bis(3‐methyl‐1‐phenyl‐1H‐pyrazol‐5(4H)‐one) (compound 3 ) and 5‐methyl‐4‐(phenyl(2‐((3‐phenylallylidene)amino)phenylamino)methylene)‐2‐phenyl‐2,4‐dihydro‐pyrazol‐3‐one (compound 4 ) were synthesized by interaction of compound 2 with PMBP and cinnamaldehyde in an ethanolic medium, respectively. The molecular structures of the title compounds were first characterized by single‐crystal X‐ray diffraction, mass spectrometry, and elemental analysis. The title compounds were tested for antibacterial activity (Escherichia coli, Staphylococcus aureus, and Bacillus subtilis) by disk diffusion method.