Synthesis and reactions of 3‐amino‐2‐methyl‐3H‐[1,2,4]triazolo[5,1‐b]‐quinazolin‐9‐one and 2‐hydrazino‐3‐phenylamino‐3H‐quinazolin‐4‐one

The reaction of 3‐N‐(2‐mercapto‐4‐oxo‐4H‐quinazolin‐3‐yl)acetamide ( 1 ) with hydrazine hydrate yielded 3‐amino‐2‐methyl‐3H‐[1,2,4]triazolo[5,1‐b]quinazolin‐9‐one ( 2 ). The reaction of 2 with o‐chlorobenzaldehyde and 2‐hydroxy‐naphthaldehyde gave the corresponding 3‐arylidene amino derivatives 3 and 4 , respectively. Condensation of 2 with 1‐nitroso‐2‐naphthol afforded the corresponding 3‐(2‐hydroxy‐naphthalen‐1‐yl‐diazenyl)‐2‐methyl‐3H‐[1,2,4]triazolo[5,1‐b]quinazolin‐9‐one ( 5 ), which on subsequent reduction by SnCl₂ and HCl gave the hydrazino derivative 6. Reaction of 2 with phenyl isothiocyanate in refluxing ethanol yielded thiourea derivative 7. Ring closure of 7 subsequently cyclized on refluxing with phencyl bromide, oxalyl dichloride and chloroacetic acid afforded the corresponding thiazolidine derivatives 8, 9 and 10 , respectively. Reaction of 2‐mercapto‐3‐phenylamino‐3H‐quinazolin‐4‐one ( 11 ) with hydrazine hydrate afforded 2‐hydrazino‐3‐phenylamino‐3H‐quinazolin‐4‐one ( 12 ). The reactivity 12 towards carbon disulphide, acetyl acetone and ethyl acetoacetate gave 13, 14 and 15 , respectively. Condensation of 12 with isatin afforded 2‐[N‐(2‐oxo‐1,2‐dihydroindol‐3‐ylidene)hydrazino]‐3‐phenylamino‐3H‐quinazolin‐4‐one ( 16 ). 2‐(4‐Oxo‐3‐phenylamino‐3,4‐dihydroquinazolin‐2‐ylamino)isoindole‐1,3‐dione ( 17 ) was synthesized by the reaction of 12 with phthalic anhydride. All isolated products were confirmed by their ir, ¹H nmr, ¹³C nmr and mass spectra.     

Synthesis of substituted 3‐phenyl‐6h‐pyrazolo[4,3‐d]isoxazoles from corresponding 4‐benzoyl‐5‐hydroxypyrazoles

Treatment of 1,(3)‐(di)substituted 4‐benzoyl‐5‐hydroxypyrazoles with phosphorus oxychloride affords the corresponding 4‐benzoyl‐5‐chloropyrazoles. Reaction of the latter with hydroxylamine leads to oximes, which can be cyclized to novel 3‐phenyl‐6H‐pyrazolo[4,3‐d]isoxazoles by treatment with sodium hydride in dimethyl formamide. Detailed nmr spectroscopic studies (¹H, ¹³C) with all obtained compounds are presented.     

1H‐4,5,6,7‐tetrahydro‐1,3‐diazepines. Part I: Synthesis,spectral and chemical properties of 1,2‐diaryl derivatives

The synthesis of several 1,2‐diaryl‐1H‐4,5,6,7‐tetrahydro‐1,3‐diazepines 1 by cyclization of N‐aryl‐N'‐benzoyltetramethylenediamines 2 is described. Two alternative synthetic routes to obtain precursors 2 are discussed, being that which employes pyrrolidine as starting material the most convenient. Nucleophilic attack of compounds 1 on methyl iodide affords 1,2‐diaryl‐1H‐4,5,6,7‐tetrahydro‐1,3‐diazepinium iodides 3 . ¹H‐nmr spectra of these compounds are unequivocally assigned by means of NOESY experiments, ¹H‐nmr spectra of compounds 1 and 3 are analyzed and compared inter se and with those of compounds 1 run in the presence of trifluoroacetic acid‐d. Reduction of compounds 1 with borane leads regiospecifically to N‐aralkyl‐N'‐aryltetramethylenediamines 7 .     

Synthesis of Some Novel 2‐Anilinothiophene, 2,3′‐Bithienyl and Thienylthiopyridine Derivatives Resistance to Penicillium Digitatum Effect the Fruit

Reaction of benzotriazol‐1‐yl acetone 1 with phenyl isothiocyanate followed with α‐chloroacetone or ethyl‐α‐chloroacetate afforded 2‐anilinothiophenes 3 or 4 , respectively. Treatment of 3 with malononitrile at different reaction conditions afforded 6 or 7 . Reaction of 1 with CS₂ in DMF and phenacylbromide afforded S‐alkylated thiophene 10 . Reactions of the latter compound with different active methylene nitriles afforded thienylthiopyridine derivatives 14 and 15 . Condensation of 10 with hydrazine hydrate afforded hydrazon derivative 16 . Reaction of thiophene 17 with formamide in DMF afforded 19 which converted to N‐thienylpyrimidine 20 when treated with malononitrile. The structure of the newly synthesized compounds has been established on the basis of their analytical and spectral data. The compounds were also investigated for antibacterial and antifungal activities.     

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.     

New routes to the synthesis of pyridazinone,ethoxypyridine, pyrazole and pyrazolo[1,5‐a]pyrimidine derivatives incorporating a benzotriazole moiety

A new approach to the synthesis of pyridazinone, ethoxypyridine, pyrazole and 7‐aminopyrazolo‐[1,5‐a]pyrimidine derivatives. The structure of the newly synthesized compounds was elucidated by elemental analyses, ir, ¹H nmr spectra and in some cases by ¹³C nmr investigations.     

Synthesis and Antimicrobial Evaluation of Some Novel 5‐Phenyl‐5H‐thiazolo[4,3‐b][1,3,4]thiadiazole Systems

Condensation of 2‐amino‐5‐phenyl‐5H‐thiazolo[4,3‐b] [1,3,4] thiadiazoles ( 1 ) with some carboxylic acid derivatives furnished corresponding compounds 2–4 , respectively. Alkylation of 1 with benzoylchloride and 4‐chlorobenzyl chloride afforded thiazolo[4,3‐b][1,3,4]thiadiazole derivatives 5 and 6 , respectively. Similarly, transformation of 1 with chloroacetyl chloride yielded chloroacetamide derivative 7 . The later compound was subjected to react with potassium thiocyanate or piperazine whereby, the binary thiazolidinone derivative 8 and N ¹ ,N⁴‐disubstituted piperazine 9 were produced, respectively. Also, the reactivity of 1 toward various active methylene reagents was investigated. Accordingly, our attempts to synthesize the tricyclic heterocyclic system 10 , 11′ , 12 ^′ by reaction of 1 with chloroacetonitrile, 4‐oxo‐4‐phenylbutanoic acid and/or diethylmalonate in presence of acetyl chloride was furnished 10 , 11 , and 12 . The newly synthesized compounds were screened as antimicrobial agent.     

Synthesis and Reactivity of 3‐oxoprop‐1‐en‐1‐olate Derivative as a Building Block for the Synthesis of Azole and Azine Derivatives

Several new heterocyclic compounds such as 7‐substituted pyrazolo[1,5‐a ]pyrimidine ( 5a–e ) derivatives have been synthesized by the reactions of the versatile unreported sodium 3‐(4‐methyl‐2‐(4‐methylphenylsulfonamido)thiazol‐5‐yl)‐3‐oxoprop‐1‐en‐1‐olate (2) with amino heterocyclic ( 3a–e ) derivatives. Reaction of (2) with hydrazonyl halide ( 7a–d ) and hydroximoyl chloride ( 11a,b ) derivatives followed by reaction with hydrazine hydrate afforded pyrazolo[3,4‐d ]pyridazine and isoxazolo[3,4‐d ]pyridazine derivatives, respectively incorporating a thiazole moiety have been described. All newly synthesized compounds were elucidated by considering the data of both elemental and spectral analysis.     

Efficient synthesis and spectral determination of 11‐[(o‐ m‐ and p‐substituted)‐phenyl]‐8‐chloro‐3,3‐dimethyl‐2,3,4,5,10,11‐hexahydro‐1H‐dibenzo[b,e][1,4]diazepin‐1‐ones

A new synthesis to obtain eleven novel derivatives of 11‐[(o‐ m‐ and p‐substituted)‐phenyl]‐8‐chloro‐3,3‐dimethyl‐2,3,4,5,10,11‐hexahydro‐1H‐dibenzo[b,e][1,4]diazepin‐1‐ones with possible pharmacological activity in the central nervous system in two efficient steps has been developed. The final products were obtained by condensation and cyclization between 3‐[4‐chloro‐1,2‐phenylenediamine]‐5,5‐dimethyl‐2‐cyclohexenone with (o‐ m‐ and p‐substituted)benzaldehyde. The structure of all products was corroborated by ir, ¹H‐nmr, ¹³C‐nmr and high resolution in ms.     

A facile synthesis and antimicrobial activity of 2,10‐dichloro‐6‐(aryloxy/thiophenoxy)‐4,8‐dinitrodibenzol[d,g][1,3,6,2]‐dioxathiaphosphocin‐ 6‐oxides

Novel 6‐substituted 2,10‐dichloro‐4,8‐dinitrodibenzo[d,g][1,3,6,2]dioxathiaphosphocin‐6‐oxides 4 were synthesized by reacting 5,5′‐dichloro‐3,3′‐dinitro‐2,2′‐dihydroxydiphenyl sulfide ( 2 ) with different aryl phosphorodichloridates, trichloromethylphosphonic dichloride and O‐2‐chloroethyl phosphoryldichloride (3) in the presence of triethylamine at 55–60°. Some of these compounds are prepared by reacting the monochloride, 2,6,10‐trichloro‐4,8‐dinitrodibenzo[d,g][1,3,6,2]dioxathiaphosphoein‐6‐oxide ( 5 ) in situ with substituted phenols and thiols. 5 is prepared by condensing 2 with phosphorus oxychloride. The ¹H nmr chemical shifts of the dibenzodioxathiaphosphocin moiety indicates the presence of more than one conformer in solution. However the presence of more than one conformer in each example cannot be entirely eliminated. Interestingly 4d on oxidation to 12‐sulphone by H₂O₂ in acetic acid medium yielded only 12‐sulphoxide 6a . The ir, ¹H, ¹³C, ³¹P nmr and mass spectral data are discussed. Some of these compounds were screened for antifungal activity against Curvularia lunata and Aspergillus niger and antibacterial activity on Bacillus subtilis and Klebsiella pneumoniae. A few of them possess significant activity.     

New One Pot‐synthesis of Functionally Substituted Pyridines from Enaminoketones

Several new pyridine derivatives were prepared via reaction of enaminoketones 1a , 1b , 1c , 1d with active hydrogen reagents. Reaction of the enaminoketones 1a , 1b , 1c with 4‐acetyl‐1,5‐dimethyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐one 2a yielded the pyridines 3a , 3b , 3c . Condensation of the enaminonitrile 1d with compounds 2b , 2c , 2d and compound 8 gave the pyridine derivatives 6a , 6b , 6c and 10 respectively. Also, (3‐(dimethylamino)acryloyl)‐2H‐chromen‐2‐one 1a reacted with active methylenes in diethyl 3‐oxopentanedioate 12 and 4‐methyl‐6‐oxo‐2‐thioxo‐1,2,5,6‐tetrahydropyridine‐3‐carbonitrile 15 to afford the pyridine derivatives 14 and 16 respectively.     

Synthesis and spectral properties of 7‐chloro‐5‐[(o‐ and p‐R1)phenyl]‐1‐R2‐3H‐[1,4]benzodiazepin‐2‐ones

A series of twelve new 7‐chloro‐5‐[(o‐ and p‐R₁)phenyl]‐1‐R₂‐3H‐[1,4] benzo‐diazepin‐2‐ones, which have possible pharmacological properties were synthesized. The synthesis of all the final compounds was carried out by four steps. The structure of all final products was corroborated by ir, ¹H nmr, ¹³C nmr and ms, and have been obtained in 35‐94% yield.     

Microwave‐assisted three‐component synthesis and in vitro antifungal evaluation of 6‐cyano‐5,8‐dihydropyrido[2,3‐d]pyrimidin‐4(3H)‐ones

The reaction of 6‐aminopyrimidin‐4‐ones 1 with benzaldehydes 2 and β‐aminocrotononitrile 3 or benzoylacetonitrile 4 under microwave irradiation in dry media yields the 6‐cyano‐5,8‐dihydropyrido[2,3‐d]‐pyrimidinones 5a‐t . The structure of the synthesized compounds was determined on the basis of nmr measurements, especially by ¹H,¹H?, ¹H,¹³C COSY, DEPT and NOESY experiments. In contrast with other pyrido‐[2,3‐d]pyrimidine derivatives, these compounds did not show any antifungal in vitro activity up to 250 μg/mL.     

New domino‐reaction for the synthesis of N4‐(5‐aryl‐1,3‐oxathiol‐2‐yliden)‐2‐phenylquinazolin‐4‐amines and 4‐[4‐aryl‐5‐(2‐phenylquinazolin‐4‐yl)‐1,3‐thiazol‐2‐yl]morpholine

The model morpholine‐1‐carbothioic acid (2‐phenyl‐3H‐quinazolin‐4‐ylidene) amide (1) reacts with phenacyl bromides to afford N⁴‐(5‐aryl‐1,3‐oxathiol‐2‐yliden)‐2‐phenylquinazolin‐4‐amines (4) or N⁴‐(4,5‐diphenyl‐1,3‐oxathiol‐2‐yliden)‐2‐phenyl‐4‐aminoquinazoline ( 5 ) by a thermodynamically controlled reversible reaction favoring the enolate intermediate, while the 4‐[4‐aryl‐5‐(2‐phenylquinazolin‐4‐yl)‐1,3‐thiazol‐2‐yl]morpholine ( 8 ) was produced by a kinetically controlled reaction favoring the C‐anion intermediate. ¹H nmr, ¹³C nmr, ir, mass spectroscopy and x‐ray identified compounds ( 4 ), ( 5 ) and ( 8 ).     

Synthesis and antimicrobial activity of 2‐substituted‐2,3‐dihydro‐5‐propoxy‐1H‐1,3,2‐benzodiazaphosphole 2‐Oxides

Several 2‐alkylcarbamato/thiocarbamato/aryloxy/trichloromethyl‐2,3‐dihydro‐5‐propoxy‐1H‐1,3,2‐benzodiazaphosphole 2‐oxides ( 4 and 6 ) were synthesised by reacting 4‐propoxy‐o‐phenylenediamine ( 1 ) with various N‐dichlorophosphinyl carbamates ( 3 ), aryl phosphorodichloridates ( 5a‐f ) and trichloromethyl phosphonic dichloride ( 5g ) in the presence of triethylamine at 45‐65 °C. Their ir, ¹H, ¹³C, ³¹P nmr and mass spectral data are discussed. The compounds were screened for antifungal activity against Curvularia lunata and Aspergillus niger and for antibacterial activity against Bacillus subtilis and Escherichia coli. Most of these compounds exhibited moderate activity in the assays.     

Elaboration of 1,8‐naphthyridine‐2,7‐dicarboxaldehyde into novel 2,7‐dimethylimine derivatives

The known 1,8‐naphthyridine‐2,7‐dicarboxaldehyde was prepared by SeO₂ oxidation of 2,7‐dimethyl‐1,8‐naphthyridine. The dimethylated naphthyridine molecule was assembled from an adaptation of the Skraup synthesis using 2‐amino‐6‐methylpyridine and crotonaldehyde to afford a reproducible 37% yield, and constitute a significant advance over the literature of this reaction. The condensation of 1,8‐naph‐thyridine‐2,7‐dicarboxaldehyde with various primary amines (R = ‐C₆H₁₁, ‐CH₂C₆H₅, ‐C(CH₃)₃, ‐C₁₀H₁₅, and CH₂CH₂SCH₂CH₃) in alcohol affords diimines 1(a‐e) . The inherent crystallinity of 1(a‐e) affords pure compounds in reasonable to excellent yields (ca. 70%) after evaporation of solvent and recrystallization. The anticipated spectroscopic features of (N=C‐H) ¹H nmr shift and v(C=N) in the ir spectrum appear around 8.50 δ and 1640 cm^?1, respectively, for the series 1(a‐e) . These novel naph‐thyridines typically display the signature ¹H nmr doublets at ca. 8.15‐8.30 δ ascribed to the 3 and 4 naphthyridine protons, consistent with a mirror plane (through the quaternary carbons) perpendicular to the naphthyridine plane, and syn, syn relationships of the naphthyridine moiety with each imine nitrogen lone pair. Complexation studies of 1(a‐e) with transition metals of biological relevance such as copper(I) and copper(II) will be reported elsewhere.     

Synthese und Reaktivität von 2‐Brom‐1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol Molekülstruktur von Bis(1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol‐2‐yl)

Synthesis and Reactivity of 2‐Bromo‐1,3‐diethyl‐2,3‐dihydro‐1 H ‐1,3,2‐benzodiazaborole Molecular Structure of Bis(1,3‐diethyl‐2,3‐dihydro‐1 H ‐1,3,2‐benzodiazaborol‐2‐yl The reaction of a slurry of calcium hydride in toluene with N,N′‐diethyl‐o‐phenylenediamine ( 1 ) and boron tribromide affords 2‐bromo‐1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol ( 2 ) as a colorless oil. Compound 2 is converted into 2‐cyano‐1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborole ( 3 ) by treatment with silver cyanide in acetonitrile. Reaction of 2 with an equimolar amount of methyllithium affords 1,3‐diethyl‐2‐methyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborole ( 4 ). 1,3,2‐Benzodiazaborole is smoothly reduced by a potassium‐sodium alloy to yield bis(1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol‐2‐yl] ( 7 ), which crystallizes from n‐pentane as colorless needles. Compound 7 is also obtained from the reaction of 2 and LiSnMe₃ instead of the expected 2‐trimethylstannyl‐1,3,2‐benzodiazaborole. N,N′‐Bis(1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol‐2‐ yl)‐1,2‐diamino‐ethane ( 6 ) results from the reaction of 2 with Li(en)C≡CH as the only boron containing product. Compounds 2 – 4 , 6 and 7 are characterized by means of elemental analyses and spectroscopy (IR, ¹H‐, ¹¹B{¹H}‐, ¹³C{¹H}‐NMR, MS). The molecular structure of 7 was elucidated by X‐ray diffraction analysis.     

Two‐step synthesis of new 1,2,4,5‐tetrahydrospiro‐[3H‐2‐benzazepine‐3,4′‐piperidines] from 4‐iminopiperidines

New spiro[3H‐2‐benzazepine‐3,4′‐piperidines] and their precursors, N‐substituted 4‐allyl‐4‐N‐benzyl‐aminopiperidines, have been prepared as potential psychotic agents from readily available 4‐iminopiperidines, by a sequence of reactions that included nucleophilic addition of Grignard reagents and Bronsted acid‐mediated intramolecular cyclisation. Some of the compounds prepared have been tested in albine mice for spontaneous motor activity. All compounds prepared were characterized by ir and ¹H nmr spectroscopies and cg‐ms spectrometry.     

Heterocycles Derived from 5‐(2‐Aminothiazol‐4‐yl)‐8‐hydroxyquinoline: Synthesis and Antimicrobial Activity

5‐(2‐Aminothiazol‐4‐yl)‐8‐hydroxyquinoline 2 has been synthesized by treating thiourea with 5‐chloroacetyl‐8‐hydroxyquinoline 1 . The amine 2 was treated with aromatic aldehydes to furnish schiff bases 6a‐c which on treatment with phenyl isothiocyanate gave the corresponding thiazolo‐s‐triazines 7a‐c . Reaction of 2 with phenyl isothiocyanate gave the corresponding aminocarbothiamide derivative 8 which on reaction with malonic acid in acetyl chloride afforded thiobarbituric acid derivative 9 . Coupling of 9 with diazonium salt gave the phenyl hydrazono derivative 10 . However, reaction of 2 with carbon disulphide and methyl iodide afforded dithiocarbamidate 12 which on treatment with ethylenediamine, o‐aminophenol and/or phenylenediamine gave the aminoazolo derivatives 13–15 , respectively. Other substituted fused thiazolopyrimidines 16–20 have been also prepared by the reaction of 2 with some selected dicarbonyl reagents. The characterisation of synthesized compounds has been done on the basis of elemental analysis, IR, ¹H‐NMR and mass spectral data. All the newly synthesized compounds have been screened for their antimicrobial activities.     

Solvent‐free microwave synthesis of bis‐pyrazolo[3,4‐b:4′,3′‐e]‐pyridines and study of their antifungal properties

The synthesis of a series of bis‐pyrazolo[3,4‐b:4′,3′‐e]pyridines ( 3 ) in the reaction of 5‐amino‐3‐methyl‐1‐phenylpyrazole ( 1 ) with aldehydes ( 2 ) under microwave irradiation and solvent‐free conditions is described. The structure elucidation of the products is based on detailed nmr analysis of experiments such as ¹H‐COSY, NOESY, DEPT, HSQC and HMBC. These compounds showed moderate antifungal in vitro activity against dermatophytes.