Synthesis and Characterization of Novel 1‐Methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazole Derivatives

A series of novel 1‐methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles was synthesized in three steps from 5‐(1‐methyl‐1H‐indazol‐3‐yl)‐4‐phenyl‐2H‐1,2,4‐triazole‐3(4H)‐thiones. 5‐(1‐Methyl‐1H‐indazol‐3‐yl)‐4‐phenyl‐2H‐1,2,4‐triazole‐3(4H)‐thiones were converted into 1‐methyl‐3‐(5‐(methylsulfonyl)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles upon methylation followed by treatment with aq. KMnO₄. The reaction of 1‐methyl‐3‐(5‐(methylsulfonyl)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles with Raney nickel resulted in desulphonylation to afford corresponding 1‐methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles. All the new synthesized compounds were characterized by spectral techniques.     

Synthesis of 3‐Acetyl‐4‐hydroxy‐1‐phenylpyridin‐2(1H)‐one Derivatives

The cyclization of aryl ketone anilides 3 with diethyl malonate to affords 4‐hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c]‐pyridin‐2,5‐diones 4 in good yields. 3‐Acetyl‐4‐hydroxy‐1‐phenylpyridin‐2(1H)‐ones 5 are obtained by ring‐opening reaction of 4‐hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c]‐pyridin‐2,5‐diones 4 in the presence of 1,2‐diethylene glycol. The reaction of 3‐acetyl‐4‐hydroxy‐1‐phenylpyridin‐2(1H)‐ones 5 with hydroxylamine hydrochloride produces 4‐hydroxy‐3‐[N‐hydroxyethanimidoyl]‐1‐phenylpyridin‐2(1H)‐ones 6 from which 3‐alkyloxyiminoacetyl‐4‐hydroxy‐1‐phenylpyridin‐2(1H)‐ones 7 are obtained by reacting with alkyl bromides or iodides in the presence of anhydrous potassium carbonate with moderate yields. The similar compounds can be synthesized on refluxing 3‐acetyl‐4‐hydroxy‐1‐phenylpyridin‐2(1H)‐ones 5 with substituted hydroxylamine hydrochloride in the presence of sodium bicarbonate with good yields. Most of the synthesized compounds are characterized by IR and NMR spectroscopic methods.     

Synthesis of Acetyl and Iodo Derivatives of 4‐Hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c]pyridine‐2,5‐diones and 4‐Hydroxy‐1‐phenylpyridin‐2(1H)‐ones

A simple and efficient method has been described for the synthesis of acetyl and iodo derivatives of 4‐hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c ]pyridine‐2,5‐diones 1 and 4‐hydroxy‐1‐phenylpyridin‐2(1H )‐ones 5 . Compounds 1 with phenyl and alkyl substituent at C(7) and C(8), respectively, can be easily acetylated by refluxing in a mixture of acetic acid and polyphosphoric acid to give 3‐acetyl‐4‐hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c ]pyridine‐2,5‐diones 2 in excellent yields. Compounds 1 and 5 can be iodinated with iodine and anhydrous sodium carbonate in boiling dioxane to give 4‐hydroxy‐3‐iodo‐6‐phenyl‐6H‐pyrano[3,2‐c ]pyridine‐2,5‐diones 3 and 4‐hydroxy‐3‐iodo‐1‐phenylpyridin‐2(1H )‐ones 6 , respectively, in good yields. The structures were confirmed using infrared, nuclear magnetic resonance , and elemental analysis.     

Heterocyclic synthesis: A convenient route to some 2‐mercepto 1,3,4‐oxadiazole and green chemistry microwave‐induced one‐pot synthesis of 2‐aryl 1,3,4‐oxadiazole in quinazolone and their antibacterial and antifungal activity

Several 6‐substituted‐3‐[(5‐mercepto‐1,3,4‐oxadiazol‐2‐yl)methyl]‐2‐substituted quinazolin‐4(3H)‐one or 6‐substituted‐3‐[4‐(5‐mercepto‐1,3,4‐oxadiazol‐2‐yl)phenyl]‐2‐substituedquinazolin‐4(3H)‐one 2(a‐l) and 6‐substituted‐3‐[(5‐phenyl‐1,3,4‐oxadiazol‐2‐yl)methyl]‐2‐substitutedquinazolin‐4(3H)‐one or 6‐substi‐tuted‐3‐[4‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐yl) phenyl]‐2‐substitutedquinazolin‐4(3H)‐one 3(a‐l) were synthesized using conventional and microwave techniques respectively and were screened for antibacterial and antifungal activity.     

Synthesis of Some New Heterocycles Derived from Ethyl 7‐Amino‐3‐(3‐methyl‐5‐oxo‐1‐phenyl‐2‐pyrazolin‐4‐yl)‐5‐aryl‐5H‐thiazolo[3,2‐a]pyrimidine‐6‐carboxylate of Biological Importance

Ethyl 7‐amino‐3‐(3‐methyl‐5‐oxo‐1‐phenyl‐2‐pyrazolin‐4‐yl)‐5‐aryl‐5H‐thiazolo[3,2‐a]pyrimidine‐6‐carboxylate was synthesized by the reaction of 4‐(2‐aminothiazol‐4‐yl)‐3‐methyl‐5‐oxo‐1‐phenyl‐2‐pyrazoline with arylidene ethyl cyanoacetate and it transformed to related fused heterocyclic systems via reaction with various reagents. The biological activities of these compounds were evaluated.     

Investigation the chemical reactivity of positions N‐3, C‐5 and C6‐methyl group in biginelli type compounds and synthesis of new dihydropyrimidine derivatives

The compounds 5‐ethoxycarbonyl‐1,6‐dimethyl‐4‐(3‐nitrophenyl)‐3,4‐dihydropyrimidin‐2(lH)‐one (5) and 5‐ethoxycarbonyl‐1‐phenyl‐6‐methyl‐4‐(3‐nitrophenyl)‐3,4‐dihydropyrimidin‐2(lH)‐one (1) were prepared by the Biginelli condensation method and they converted to eight N‐3 substituted dihydropyrimidines using NaH and various electrophiles (ClCO₂Et, TsCl, Ac₂O, AcCl and PhCOCl). Compound (1) was mono‐brominated at the C₆‐methyl group using bromine solution. Reaction of the bromo derivative with amino nucleophiles such as methyl amine and cyclohexyl amine produced two pyrrolo‐pyrimidine derivatives. All the compounds except 5‐ethoxycarbonyl‐1‐phenyl‐6‐methyl‐4‐(3‐nitrophenyl)‐3,4‐dihydropyrimidin‐2(l_H)‐one ( 4 ) were purified by recrystallization methods. The structure of all the new compounds was confirmed using FT‐ir,¹H nmr, ¹³C nmr spectral and elemental analyses methods.     

Generation and reactivity of 3‐carbethoxy‐5‐phenyl‐5H,7H‐thiazolo[3,4‐c]oxazol‐4‐ium‐1‐olate

3‐Carbethoxy‐5‐phenyl‐5H,7H‐thiazolo[3,4‐c]oxazol‐4‐ium‐1‐olate was generated from (2R,4R)‐N‐ethoxyoxalyl‐2‐phenylthiazolidine‐4‐carboxylic acid and its reactivity studied. This münchnone showed low reactivity as dipole although from the reaction with dimethyl acetylenedicarboxylate the corresponding (3R)‐3‐phenyl‐17H,3H‐pyrrolo[1,2‐c]thiazole‐5,6,7‐tricarboxylate could be isolated. The thermolysis of (2R,4R)‐N‐ethoxyoxalyl‐2‐phenylthiazolidine‐4‐carboxylic acid in refluxing acetic anhydride led to the synthesis of N‐(1‐ethoxycarbonyl‐2‐phenylvinyl)‐2‐phenyl‐4‐thioxo‐1,3‐thiazolidine. The structure of methyl (2R,4R)‐N‐ethoxyoxalyl‐2‐phenylthiazoliddine‐4‐carboxylate was determined by X‐ray crystallography.     

Synthesis and Characterization of Some Novel Phosphorylated 4‐Oxo‐2‐phenylquinazolines

Some novel phosphines, aminophosphines and their oxides, and derived phosphorus acids bearing 4‐oxo ‐ 2‐phenylquinazolin‐3‐yl moiety were synthesized. The methodology depended on the reaction of each 2‐phenylquinazolin‐4(3H)‐one ( 1 ) and 3‐amino‐2‐phenyl‐quinazolin‐4(3H)‐one ( 2 ) with (Ph)₂PCl, PhPCl₂, and PhP (O)Cl₂ in different ratios. The synthesized compounds were characterized by elemental analysis and spectral tools.     

Studies on the Reactivity of Amino‐1‐(6‐phenyl‐pyridazin‐3‐yl)‐1H‐pyrazole‐4‐carboxylic Acid Hydrazide Towards Some Reagents for Biological Evaluation

Novel 5‐amino‐1‐(6‐phenyl‐pyridazin‐3‐yl)‐1H‐pyrazole‐4‐carboxylic acid ethyl ester ( 2 ) was formed using (6‐phenyl‐pyridazin‐3‐yl)‐hydrazine ( 1 ) and ethyl(ethoxymethylene)cyanoacetate. The β‐enaminoester derivative 2 was in turn used as precursor for the preparation of 1‐(6‐phenyl‐pyridazin‐3‐yl)‐pyrazoles ( 3 , 4 , 7 , 8 , 9 , 10 , 11 , 12 , 15 , 16 ), 1‐(6‐phenyl‐pyridazin‐3‐yl)‐pyrazolo[3,4‐d]pyrimidines ( 5 , 6 , 14 ) and 1‐(6‐phenyl‐pyridazin‐3‐yl)‐pyrazolo[3,4‐d][1,2,3]triazine ( 13 ). The in vitro antimicrobial activity of the synthesized compounds was evaluated by measuring the inhibition zone diameters where some of them showed potent antimicrobial activity in compared with well‐known drugs (standards).     

1,3‐Dipolar Cycloaddition Reactions of Organic Azides with Morpholinobuta‐1,3‐dienes and with an α‐Ethynyl‐enamine

The cycloaddition of organic azides with some conjugated enamines of the 2‐amino‐1,3‐diene, 1‐amino‐1,3‐diene, and 2‐aminobut‐1‐en‐3‐yne type is investigated. The 2‐morpholinobuta‐1,3‐diene 1 undergoes regioselective [3+2] cycloaddition with several electrophilic azides RN₃ 2 ( a , R=4‐nitrophenyl; b , R=ethoxycarbonyl; c , R=tosyl; d , R=phenyl) to form 5‐alkenyl‐4,5‐dihydro‐5‐morpholino‐1H‐1,2,3‐triazoles 3 which are transformed into 1,5‐disubstituted 1H‐triazoles 4a , d or α,β‐unsaturated carboximidamide 5 (Scheme 1). The cycloaddition reaction of 4‐[(1E,3Z)‐3‐morpholino‐4‐phenylbuta‐1,3‐dienyl]morpholine ( 7 ) with azide 2a occurs at the less‐substituted enamine function and yields the 4‐(1‐morpholino‐2‐phenylethenyl)‐1H‐1,2,3‐triazole 8 (Scheme 2). The 1,3‐dipolar cycloaddition reaction of azides 2a – d with 4‐(1‐methylene‐3‐phenylprop‐2‐ynyl)morpholine ( 9 ) is accelerated at high pressure (ca. 7–10 kbar) and gives 1,5‐disubstituted dihydro‐1H‐triazoles 10a , b and 1‐phenyl‐5‐(phenylethynyl)‐1H‐1,2,3‐triazole ( 11d ) in significantly improved yields (Schemes 3 and 4). The formation of 11d is also facilitated in the presence of an equimolar quantity of tBuOH. The three‐component reaction between enamine 9 , phenyl azide, and phenol affords the 5‐(2‐phenoxy‐2‐phenylethenyl)‐1H‐1,2,3‐triazole 14d .     

Pseudopolymorphs of 2,6‐diaminopyrimidin‐4‐one and 2‐amino‐6‐methylpyrimidin‐4‐one: one or two tautomers present in the same crystal

The derivatives of pyrimidin‐4‐one can adopt either a 1H‐ or a 3H‐tautomeric form, which affects the hydrogen‐bonding interactions in cocrystals with compounds containing complementary functional groups. In order to study their tautomeric preferences, we crystallized 2,6‐diaminopyrimidin‐4‐one and 2‐amino‐6‐methylpyrimidin‐4‐one. During various crystallization attempts, four structures of 2,6‐diaminopyrimidin‐4‐one were obtained, namely solvent‐free 2,6‐diaminopyrimidin‐4‐one, C₄H₆N₄O, (I), 2,6‐diaminopyrimidin‐4‐one–dimethylformamide–water (3/4/1), C₄H₆N₄O·1.33C₃H₇NO·0.33H₂O, (Ia), 2,6‐diaminopyrimidin‐4‐one dimethylacetamide monosolvate, C₄H₆N₄O·C₄H₉NO, (Ib), and 2,6‐diaminopyrimidin‐4‐one–N‐methylpyrrolidin‐2‐one (3/2), C₄H₆N₄O·1.5C₅H₉NO, (Ic). The 2,6‐diaminopyrimidin‐4‐one molecules exist only as 3H‐tautomers. They form ribbons characterized by R²₂(8) hydrogen‐bonding interactions, which are further connected to form three‐dimensional networks. An intermolecular N—H...N interaction between amine groups is observed only in (I). This might be the reason for the pyramidalization of the amine group. Crystallization experiments on 2‐amino‐6‐methylpyrimidin‐4‐one yielded two isostructural pseudopolymorphs, namely 2‐amino‐6‐methylpyrimidin‐4(3H)‐one–2‐amino‐6‐methylpyrimidin‐4(1H)‐one–dimethylacetamide (1/1/1), C₅H₇N₃O·C₅H₇N₃O·C₄H₉NO, (IIa), and 2‐amino‐6‐methylpyrimidin‐4(3H)‐one–2‐amino‐6‐methylpyrimidin‐4(1H)‐one–N‐methylpyrrolidin‐2‐one (1/1/1), C₅H₇N₃O·C₅H₇N₃O·C₅H₉NO, (IIb). In both structures, a 1:1 mixture of 1H‐ and 3H‐tautomers is present, which are linked by three hydrogen bonds similar to a Watson–Crick C–G base pair.     

Reactivity of (2‐methylsulfanyl‐4‐oxo‐6‐phenyl‐4h‐pyrimidin‐3‐yl)‐acetic acid methyl ester towards hydrazine hydrate and benzylamine

The title ester 1 reacted with hydrazine hydrate to give hydrazide 2 , which underwent intramolecular cyclization to yield 1‐amino‐7‐phenyl‐1H‐imidazo[1,2‐a]pyrimidine‐2,5‐dione ( 3 ) or took place in a substitution reaction with benzylamine to form N‐benzyl‐2‐(2‐benzylamino‐4‐oxo‐6‐phenyl‐4H‐pyrimidin‐3‐yl)‐acetamide ( 4 ). The reaction of ester 1 with benzylamine gave corresponding amide 7 , disubstituted derivative 4 or 1‐benzyl‐7‐phenyl‐1H‐imidazo[1,2‐a]pyrimidine‐2,5‐dione ( 8 ) depending on the reaction conditions.     

New Chiral and Achiral Imines and Bisimines Derived from 2‐Phenyl‐1H‐imidazole‐4‐carbaldehyde. Synthesis,Structural Studies and Complexation Stability Constants

Synthesis and properties of new imines and bisimines derived from 2‐phenyl‐1H‐imidazole‐4‐carbaldehyde and amines/diamines were studied. (2‐Phenyl‐1H‐imidazole‐4‐yl)methanol was oxidized to 2‐phenyl‐1H‐imidazole‐4‐carbaldehyde with better yield 55% by the modification of literature procedure. This aldehyde was condensed with the following achiral and chiral amines or 1,2‐diamines: ethanamine, propan‐1‐amine, butan‐1‐amine, 2‐methylpropan‐1‐amine, cyclohexanamine, (2R)‐ and (2S)‐3‐methylbutan‐2‐amine, (1R)‐ and (1S)‐1‐cyclohexylethanamine, (S)‐1‐aminopropan‐2‐ol, (S)‐1‐(2‐phenyl‐1H‐imidazol‐4‐yl)ethanamine, (S)‐1‐(2‐phenyl‐1H‐imidazol‐4‐yl)‐2‐methylpropan‐1‐amine, (S)‐1‐(2‐phenyl‐1H‐imidazol‐4‐yl)‐3‐methylbutan‐1‐amine, ethane‐1,2‐diamine, and (1R,2R)‐ and (1S,2S)‐cyclohexane‐1,2‐diamine. Sixteen condensation products, especially chiral imines and bisimines, were prepared by founded procedures in 45–99% of yields and characterized by the ¹H NMR spectroscopy in solution, mass spectrometry, and elemental analyses. The optical rotation values in the case of chiral ones were also observed. Stability constants of Cu(II) complexes of selected prepared imines/bisimines were determined.     

A concise synthesis of a highly substituted 6‐(1H‐benzimidazol‐1‐yl)‐5‐nitrosopyrimidin‐2‐amine: synthetic sequence and the molecular and supramolecular structures of one product and two intermediates

A concise and efficient synthesis of 6‐benzimidazolyl‐5‐nitrosopyrimidines has been developed using Schiff base‐type intermediates derived from N⁴‐(2‐aminophenyl)‐6‐methoxy‐5‐nitrosopyrimidine‐2,4‐diamine. 6‐Methoxy‐N⁴‐{2‐[(4‐methylbenzylidene)amino]phenyl}‐5‐nitrosopyrimidine‐2,4‐diamine, (I), and N⁴‐{2‐[(ethoxymethylidene)amino]phenyl}‐6‐methoxy‐5‐nitrosopyrimidine‐2,4‐diamine, (III), both crystallize from dimethyl sulfoxide solution as the 1:1 solvates C₁₉H₁₈N₆O₂·C₂H₆OS, (Ia), and C₁₄H₁₆N₆O₃·C₂H₆OS, (IIIa), respectively. The interatomic distances in these intermediates indicate significant electronic polarization within the substituted pyrimidine system. In each of (Ia) and (IIIa), intermolecular N—H…O hydrogen bonds generate centrosymmetric four‐molecule aggregates. Oxidative ring closure of intermediate (I), effected using ammonium hexanitratocerate(IV), produced 4‐methoxy‐6‐[2‐(4‐methylphenyl‐1H‐benzimidazol‐1‐yl]‐5‐nitrosopyrimidin‐2‐amine, C₁₉H₁₆N₆O₂, (II) [Cobo et al. (2018). Private communication (CCDC 1830889). CCDC, Cambridge, England], where the extent of electronic polarization is much less than in (Ia) and (IIIa). A combination of N—H…N and C—H…O hydrogen bonds links the molecules of (II) into complex sheets.     

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).     

Design and Synthesis of Novel 3‐(Phenyl)‐2‐(3‐substituted propylthio) Quinazolin‐4‐(3H)‐ones as a New Class of H1‐Antihistaminic Agents

A series of novel 3‐(phenyl)‐2‐(3‐substituted propylthio) quinazolin‐4‐(3H)‐ones were synthesized by the reaction of 2‐(3‐bromopropylthio)‐3‐(phenyl) quinazolin‐4‐(3H)‐one with various amines. The starting material, 2‐(3‐bromopropylthio)‐3‐(phenyl) quinazolin‐4‐(3H)‐one was synthesized from aniline. When tested for their in vivo H₁‐antihistaminic activity on conscious guinea pigs, all the test compounds protected the animals from histamine‐induced bronchospasm significantly. Compound 2‐(3‐(4‐methylpiperazin‐1‐yl) propylthiothio)‐3‐(phenyl) quinazolin‐4(3H)‐one ( Ph5 ) emerged as the most active compound (73.23% protection) of the series when compared with the reference standard chlorpheniramine maleate (70.09% protection). Compound Ph5 shows negligible sedation (5.01 %) compared with chlorpheniramine maleate (29.58%). Therefore, compound Ph5 can serve as the leading molecule for further development into a new class of H₁‐antihistaminic agents.     

The psuedo‐michael reaction of 2‐aminoimidazolines 2. Part 1. Synthesis and structure assignment of isomeric 5(1H)‐Oxo and 7(1H)‐Oxo‐2,3‐dihydroimidazo[1,2‐a]pyrimidine‐6‐carboxylates

The pseudo‐Michael reaction of 1‐aryl‐2‐aminoimidazolines‐2 with diethyl ethoxymethylenemalonate (DEEM) was investigated. Extensive structural studies were performed to confirm the reaction course. For derivatives with N1 aromatic substituents, it was found that the reaction course was temperature dependent. When the reaction temperature was held at ?10 °C only the formation of 1‐aryl‐7(1H)‐oxo‐2,3‐dihydroimi‐dazo[1,2‐a]pyrimidine‐6‐carboxylates ( 4 ) was observed in contrast to earlier suggestions. Under the room temperature conditions, the same reaction yielded mixtures, with varying ratio, of isomeric 1‐aryl‐7(1H)‐oxo‐ ( 4a‐4f ) and 1‐aryl‐5(1H)‐oxo‐2,3‐dihydroimidazo[1,2‐a]pyrimidine‐6‐carboxylates ( 5a‐5f ). The molecular structure of selected isomers, 4b and 5c , was confirmed by X‐ray crystallography. Frontal chro‐matography with delivery from the edge was applied for the separation of the isomeric esters. The isomer ratio of the reaction products depended on the character of the substituents on the phenyl ring. The 1‐aryl‐7(1H)‐oxo‐carboxylates ( 4a‐4f ) were preferably when the phenyl ring contained H, 4‐CH₃, 4‐OCH₃ and 3,4‐Cl₂ substituents. Chloro substitution at either position 3 or 4 in the phenyl ring favored the formation of isomers 5a‐5f . The isomer ratios were confirmed both by ¹H NMR and chromatography. The reaction of the respective hydrobromides of 1‐aryl‐2‐aminoimidazoline‐2 with DEEM, in the presence of triethylamine, gave selectively 5(1H)‐oxo‐esters ( 5a‐5f ).     

Synthesis of 1‐Amino‐5,6‐diaryl‐3‐cyano‐1H‐pyridin‐2‐ones and 6,7‐Diaryl‐4‐cyano‐3‐hydroxy‐1H‐[1,2]diazepines from Isoflavones

The one‐step cyclocondensation of substituted isoflavones (=3‐phenyl‐4H‐1‐benzopyran‐4‐ones) with cyanoacetohydrazide in the presence of KOH afforded a mixture of 1‐amino‐5,6‐diaryl‐3‐cyano‐1H‐2‐pyridin‐2‐ones and 6,7‐diaryl‐4‐cyano‐3‐hydroxy‐1H‐[1,2]diazepines.     

Synthesis of N‐amino‐3‐hydroxy‐2‐phenyl‐4(1H)‐quinolinone

2‐[(Disubstituted‐methylene)‐hydrazino] benzoic acid phenacylesters 2a‐2d , prepared from anthranilic acid phenacylester 1 , were unsuccesfully tried as starting materials for the synthesis of N‐amino‐3‐hydroxy‐2‐phenyl‐4(1H)‐quinolinone 8 . The desired compound 8 was prepared by cyclization of N‐acetyl as well as N‐benzoyl‐hydrazinobenzoic acid phenacylester 6a or 6b in polyphosphoric acid to afford N‐acylamino‐3‐hydroxy‐2‐phenyl‐4(1H)‐quinolinone 7a or 7b , respectively. Surprisingly, the acyl group was resistant to attack by both hydrochloric acid as well as sodium hydroxide solution. It could be removed by boiling the compounds 7a or 7b respectively in 50% sulphuric acid to afford the the target compound 8 .     

Two biologically active thio­phene‐3‐carbox­amide derivatives

The two title compounds, 2‐({(1Z)‐[4‐(di­methyl­amino)phenyl]methylene}amino)‐4,5‐dimethyl‐N‐(2‐methylphenyl)thiophene‐3‐carboxamide, C₂₃H₂₅N₃OS, (I), and 2‐({(1E)‐[4‐(dimethylamino)phenyl]methylene}amino)‐N‐(4‐methylphenyl)‐4,5,6,7‐tetrahydro‐1‐benzothiophene‐3‐carboxamide,C₂₅H₂₇N₃OS, (II), show antibacterial and antifungal activities. The asymmetric unit of (II) contains two crystallographically independent mol­ecules. The o‐toluidine ring in (I) lies gauche with respect to the thio­phene ring. In (II), the p‐toluidine ring is coplanar with the thio­phene ring in one mol­ecule, but is tilted from it in the other mol­ecule. Neither structure exhibits any significant intermolecular interactions, but in both, an intramolecular N—H⋯N hydrogen bond forms a pseudo‐six‐membered ring, thus locking the molecular conformation and removing conformational flexibility.