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 4,5,6,7‐Tetrabromo‐1H‐benzimidazole Derivatives

A convenient and simple method for the preparation of polybrominated benzimidazole derivatives has been described. Reaction of 4,5,6,7‐tetrabromo‐1‐(3‐chloropropyl)‐1H‐benzimidazole, obtained by alkylation of 4,5,6,7‐tetrabromo‐1H‐benzimidazole (TBBi) with 1‐bromo‐3‐chloropropane in the presence of KOH, with morpholine, aniline, benzylamine, N‐methyl piperazine, and 2‐arylpyrrolidines afforded new TBBi derivatives.     

2‐(4‐methylpyridin‐2‐yl)‐1H‐benzimidazole derivatives. Part II,lH nmr characterization

A selected series of 2‐(4‐methylpyridin‐2‐yl)‐1H‐benzimidazole derivatives, bases and cyclic mono‐ and bis‐salts, were synthesized. Complete ^'1H nmr characterization is reported. Ambiguous assignments were solved using ¹H‐¹H NOESY analysis. Significant ir and ¹H nmr data are presented concerning: i) tautomeric equilibrium of imidazole hydrogen; ii) hydrogen bonds; iii) conformational inversion of partially saturated rings.     

Synthesis and fungicidal activity of novel 1,3‐disubstituted 1H‐diazirine derivatives

A convenient method for synthesis of novel 1‐[pyrimidinyl], 1‐[1,3,5‐triazin‐2‐carbonyl], and 1‐[thiazol‐5‐carbonyl] derivatives of 3‐thioxo‐diaziridine 1 , 3 , 5 , and 7 from corresponding hydrazides, CS2, and KOH is elaborated. The highest reaction yield was observed when these initial reagents were taken in molar ratio of 1:1.7:2.0, respectively. By alkylation of compounds 1 , 3 , 5 , and 7 that proceeds exclusively at sulfur atom, the 3‐sulfanyl derivatives of 1‐[pyrimidinyl]‐, 1‐[1,3,5‐triazin‐2‐carbonyl]‐, and 1‐[thiazol‐5‐carbonyl]‐diazirines 2 , 4 , 6 , and 8 were formed. The structures of synthesized compounds were confirmed by proton and carbon nuclear magnetic resonance (NMR), mass spectra (MS), and elemental analysis. The fungicidal activities of S‐substituted derivatives were studied. Data of preliminary biological tests testify that these compounds can be of interest in search for new fungicides. J. Heterocyclic Chem., (2010).     

Synthesis and structural characterisation of 4H‐1,3‐benzothiazine derivatives

The ring‐closure reactions of N‐arylthiomethylaroylamide derivatives ( 1a‐g ) in the presence of phospho ‐rus oxychloride gave 2‐aryl‐4H‐1,3‐benzo‐thiazines (2a‐g). 2‐(3‐Chlorophenyl)‐6‐methyl‐4H‐1,3‐benzoth‐iazine ( 2b ) was reduced with Zn to obtain the corresponding 2,3‐dihydro derivative ( 3b ). Potassium permanganate oxidation of 2‐(4‐chlorophenyl)‐2,3‐diethoxy‐4H‐ ( 2e ) and 2‐(2‐fluorophenyl)‐6,7‐diefhoxy‐4H‐1,3‐benzo‐thiazines ( 2g ) gave the corresponding 4‐ones ( 4e,g ). The reactions of 2‐(4‐chlorophenyl)‐6‐mefhyl‐4H‐1,3‐benzofhiazine ( 2c ) with substituted acetyl chlorides led to linearly condensed ß‐lactams ( 5a,b ). The structures of the compounds studied were confirmed by ¹H and ¹³C NMR and by their characteristic mass spectrometric fragmentations.     

Synthesis of Novel Tetrazole Containing Quinoline and 2,3,4,9‐Tetrahydro‐1H‐β‐Carboline Derivatives

This presentation describes the successful synthesis of novel tetrazole‐based quinoline and tetrahydro‐1H‐β‐carboline derivatives via one‐pot multicomponent reactions in moderate to good yields. These reactions have presumably proceeded through Ugi‐azide or Ugi‐azide/Pictet–Spengler processes, respectively.     

A convenient synthesis of 2‐(1H‐1,2,4‐triazol‐1‐yl)‐2H‐1,4‐benzothiazine derivatives

A series of 2‐(1H‐1,2,4‐triazol‐1‐yl)‐2H‐1,4‐benzothiazines were designed and synthesized by condensation of 1,2,4‐triazole‐substituted ω‐bromoacetophenones and o‐aminothiophenols with the aid of K₂CO₃ under mild conditions with moderate to high yields. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:332–336, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20434     

A study concerning the synthesis,basicity and hydrolysis of 4‐amino‐2‐(N,N‐diethylamino)quinazoline derivatives

A group of 2‐(N,N‐diethylamino)‐4‐aminoquinazoline derivatives have been synthesized in the reaction of N¹,N¹‐diethyl‐N²‐arylchlorocarboxyamidines with cyanamide in the presence of T1Cl₄ as a catalyst. Such quinazolines decompose into the corresponding quinazolones in dilute aqueous HC1 solutions at higher temperature. Hydrolysis rates of 2‐(N,N‐diethylamino)‐4‐aminoquinazoline and 2‐(N,N‐diethylamino)‐4‐(N,N‐dimethylamino)‐quinazoline have been determined to observe the influence of substituents at the 4‐amino group upon the hydrolysis. pK_a values have been also determined for these compounds and analyzed in conjunction with the Hammett σ constants.     

Synthesis of novel 1,3‐substituted 1H‐[1,2,4]‐triazole‐3‐thiol derivatives

By means of regioselective S‐alkylation of 1H‐1,2,4‐triazole‐3‐thiol ( 1 ), a series of S‐substituted derivatives 2a‐j were synthesized. In certain conditions, the reaction of 2 with arylsulfochlorides, arylisocyanates, and quaternary ammonium salts of azines corresponding compounds were obtained 1‐arylsulfonyl‐ (3a‐d) , 1‐arylcarbonamido‐ ( 4a,b ), and 1‐azinyl‐1,2,4‐ ( 6a‐p ) triazoles. Structures of compounds were confirmed by ¹H NMR and elemental analyses. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 20:405–410, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20565     

1H‐Indazole and 2H‐indazole derivatives of androsta‐5,16‐dien‐3β‐ol

The title compounds, 17‐(1H‐indazol‐1‐yl)androsta‐5,16‐dien‐3β‐ol, (I), and 17‐(2H‐indazol‐2‐yl)androsta‐5,16‐dien‐3β‐ol, (II), both C₂₆H₃₂N₂O, have an indazole substituent at the C17 position. The six‐membered B ring of each compound assumes a half‐chair conformation. A twist of the steroid skeleton is observed and reproduced in quantum‐mechanical ab initio calculations of the isolated molecule using a molecular orbital Hartree–Fock method. In the 1H‐indazole derivative, (I), the molecules are joined in a head‐to‐head fashion via O—H...O hydrogen bonds, forming chains along the a axis. In the 2H‐indazole derivative, (II), the molecules are joined in a head‐to‐tail fashion with one of the N atoms of the indazole ring system acting as the acceptor. The hydrogen‐bond pattern consists of zigzag chains running along the b axis. Substituted steroids have proven to be effective in inhibiting androgen biosynthesis through coordination of the Fe atoms of some enzymes, and this study shows that indazole‐substituted steroids adopt twisted conformations that restrict their intermolecular interactions.     

Oxidative Dearomatization of 4,5,6,7‐Tetrahydro‐1H‐indoles Obtained by Metal‐ and Solvent‐Free Thermal 5‐endo‐dig Cyclization: The Route to Erythrina and Lycorine Alkaloids

A facile one‐pot approach based on a thermally induced metal‐ and solvent‐free 5‐endo‐dig cyclization reaction of the amino propargylic alcohols in combination with Dess–Martin periodinane‐promoted oxidative dearomatization of 4,5,6,7‐tetrahydroindole intermediates provides an efficient and robust access to 5,6‐dihydro‐1H‐indol‐2(4H)ones. Green, relatively mild and operationally simple characteristics of the synthetic sequence are the major advantages, which greatly amplify the developed methodology. The utility of obtained indolones as unified key precursors is demonstrated by the application of these products to the formal total syntheses of a whole pleiad of Erythrina‐ and Lycorine‐type alkaloids, namely (±)‐erysotramidine, (±)‐erysotrine, (±)‐erythravine, (±)‐γ‐lycorane, and abnormal erythrinanes (±)‐coccoline and (±)‐coccuvinine.     

Synthesis of new 4,5,6,7‐tetrahydro‐3H‐imidazo[4,5‐c]pyridine derivatives

The synthesis of new ligands for the H₃ histamine receptor is described. These new compounds are spinacine derivatives obtained by alkylation or Michael reaction at C6 position.     

Synthesis of 1‐H‐1,5‐benzodiazepines derivatives using SiO2/ZnCl2

A general and easy method for the synthesis of several 1‐H‐1,5‐benzodiazepines using SiO₂/ZnCl₂ under solvent‐free conditions is described. This efficient and improved method furnishes selectively and in good yields the corresponding 1‐H‐1,5‐benzodiazepines derivatives starting from o‐phenylenediamine and cyclic or acyclic ketones. The catalytic system was reused up four times, and the use of focused microwaves accelerates the reaction. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:180–185, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20674     

Syntheses of 2‐Unsubstituted 1H‐1,3‐Benzazaphospholes from N‐Formyl‐2‐bromoanilides

The phosphonylation of 2‐bromo‐formylanilides 1 with triethyl phosphite in the presence of preformed Pd(0)(triethyl phosphite)_n catalyst furnished 2‐phosphono‐formanilides 2 in good yields. Reduction with excess LiAlH₄ provided mainly N‐methyl‐2‐phosphinoanilines 3 and minor amounts of 1,2‐unsubstituted benzazaphospholes 4 . N‐Methyl‐1,3‐benzazaphospholes 5 were synthesized by the cyclocondensation of 3 with dimethylformamide dimethylacetal (DMFA). A more convenient route to 5 , avoiding the chromatographic separation of 4 , is the reduction of 1 to 2‐bromo‐N‐methylaniline 6 , followed by phosphonylation to 7 , LiAlH₄ reduction, and cyclization with DMFA. The coordination properties at σ²P of benzazaphospholes are characterized by structural data obtained by the crystal structure analysis of ( 5b )W(CO)₅.     

Synthesis and fluorescent properties of 2‐(1H‐benzimidazol‐2‐yl)‐phenol derivatives

A high yield one pot synthesis of 2‐(2‐hydroxyaryl)‐1H‐benzirrndazole derivatives by 2‐hydroxy aromatic aldehydes with aromatic 1,2‐diamines in the presence of manganese(III) acetate at room temperature was developed. Nine fluorescencers 2‐(2‐hydroxyaryl)‐1H‐benzirrndazoles with substituent(s) X (X = H, CH₃, CH₃O, Cl) and two fluorescencers 2‐(2‐hydroxyaryl)‐1H‐naphth[2,3‐d]imidazoles with substituent of H or Cl were prepared in 38–87% yield and the ultraviolet absorption and fluorescent spectra of the eleven compounds synthesized were measured in methanol. The fluorescent characteristics of the 2‐(2‐hydroxyaryl)benzimidazole derivatives prepared were investigated on the basis of excited‐state intramolecular proton transfer mechanism, Stokes' shift, quantum yield, and the relationship between fluorescent intensity and the substituents were derived.     

Synthesis of 1,3,4‐Oxadiazoles and 1,3‐Thiazolidinones Containing 1,4,5,6‐Tetrahydro‐6‐pyridazinone

The reaction of 1,4,5,6‐tetrahydro‐6‐pyridazinone‐3‐carboxylic acid hydrazides ( 1 ) with aromatic aldehydes afforded 1,4,5,6‐tetrahydro‐6‐pyridazinone‐3‐carbonyl aromatic aldehyde hydrazones ( 2a‐2g ). Heterocyclic derivatives linked 1,3,4‐oxadiazole obtained by cyclocondensation of 2a‐2g with acetic anhydride in absolute ethanol, and 2a‐2g cyclized with mercaptoacetic acid in DMF in the presence of anhydrous ZnCl₂ afforded the 1,3‐thiazolidinone derivatives. The structures of the new compounds were established by elemental analyses, IR, ¹H NMR and MS spectral data.     

Efficient One‐pot Synthesis,Antimicrobial and Docking Studies of Some Newer Tetrahydro‐4H‐benzo [1,3‐e]oxazines and Related β‐Acylamino Ketone Derivatives

A concise one‐step procedure was developed for the synthesis of some newer tetrahydro‐4H‐benzo[1,3‐e ]oxazines and β‐acylamino ketone derivatives via condensation of cyclohexanone derivative with different aromatic aldehydes and nitriles in the presence of tetrachlorosilane/zinc chloride (TCS/ZnCl₂) reagent mixture under ambient conditions. Docking studies for the synthesized benzo‐oxazine derivatives were designed and a model of highly active derivatives was mapped for the antimicrobial screening.     

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.