Novel synthesis of 3‐phenylazo‐1,5‐benzothiazepines, ‐1,5‐benzoxazepines and ‐1,5‐benzodiazepines via a one‐pot reaction

Novel polysubstituted ‐1,5‐benzothiazepine, ‐1,5‐benzoxazepine, and ‐1,5‐benzodiazepine were prepared in good yields by the reaction of hydrazono derivatives with o‐thioaminophenol, o‐aminophenol and o‐phenylenediamine via a one‐pot reaction.     

Tetrahydro‐1,5‐benzoxazepines and tetrahydro‐1H‐1,5‐benzodiazepines by a tandem reduction‐reductive amination reaction

A tandem reduction‐reductive amination reaction has been applied to the synthesis of (±)‐4‐alkyl‐2,3,4,5‐tetrahydro‐1,5‐benzoxazepines and (±)‐4‐alkyl‐1‐benzoyl‐2,3,4,5‐tetrahydro‐1H‐1,5‐benzodiazepines. The nitro aldehydes and ketones required for 1,5‐benzoxazepine ring closures were prepared by nucleophilic aromatic substitution of the alkoxides from several 3‐buten‐1‐ol derivatives with 2‐fluoro‐1‐nitrobenzene followed by ozonolysis. Precursors for the 1,5‐benzodiazepines were prepared by similar addition of N‐(3‐butenyl)benzamide anions to 2‐fluoro‐1‐nitrobenzene followed by ozonolysis. Catalytic hydrogenation of the nitro carbonyl compounds using 5% palladium‐on‐carbon in methanol then gave the target heterocycles by a tandem reduction‐reductive amination sequence. The 1,5‐benzoxazepines were isolated in high yield following chromatographic purification; the 1,5‐benzodiazepines were isolated as solids directly from the hydrogenation mixture and possessed differentiated functionality on the two nitrogen atoms.     

Hetaryl‐1,5 Benzodiazepines—Part I: Synthesis of 3‐pyrimidinyl‐ and Imidazolyl‐1,5‐benzodiazepines

Nucleophilic substitution of 3‐bromo‐4‐phenyl‐1H‐[1,5]benzodiazepin‐2‐one ( 1 ) with thiourea or guanidine in presence of potassium carbonate afforded 1,5‐benzodiazepin‐3‐ylimidothiocarbamate 2 or 1,5‐benzodiazepin‐3‐ylguanidine 3 , respectively. Pyrimidylthiobenzodiazepines 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 were obtained via the reaction of compound 2 with malononitrile dimer, diethyl malonate, methylenemalononitriles, or a mixture of an aldehyde and β‐keto esters or acetylacetone, catalyzed using ceric ammonium nitrate. Reaction of compound 2 or 3 with α‐halo esters, nitriles, and/or ketones afforded imidazoles 14 , 15 , 16 , 17 , 18 , 19 , 20 , respectively.     

New Route for the Synthesis of Hetaryl‐1,5‐benzodiazepines: Part 2

1,2,4‐Triazin‐3‐ylthio‐, 1,2,4‐triazepin‐3‐ylthio‐, 1,2,4‐triazol‐3‐ylthio‐, and 1,2,4,3‐triazaphosphol‐5‐ylthio‐1,5‐benzodiazepines 4 – 20 were prepared via the reaction of 2‐oxo‐4‐phenyl‐2,3‐dihydro‐1H‐1,5‐benzodiazepin‐3‐ylhydrazonothiocarbamate ( 2 ) with halocompounds, dicarbonyl compounds, enaminones, 4‐chlorobenzaldehyde, 4‐chlorobenzylidenemalononitriles, N,N‐dimethylformamide dimethylacetal, carbon disulfide, and 2,4‐bis(4‐methoxyphenyl)‐1,3,2,4‐dithiadiphosphetane‐2,4‐disulfide (Lawesson's reagent).     

Studies with enaminones: reactivity of 1,5‐disubstituted‐1,4‐pentadien‐3‐ones toward electrophilic reagents. a novel route to azolylazines,benzofuranals, pyranones

Several new enaminodienones prepared from substituted acetone and dimethylformamide dimethylacetal were used as precursors for synthesis of pyridines, pyranones and benzofurans.     

Studies with 2‐arylhydrazononitriles: Further investigations on reactivity of 2‐arylhydrazononitriles towards hydroxylamine

The utilization of arylhydrazononitriles ( 6‐9 ) for synthesis of azoles is demonstrated. Thus, arylazomalononitriles ( 6 ) reacted with hydroxylamine hydrochloride to afford isoxazol‐5‐imine ( 10 ), amidoxime ( 12 ) and bis‐amidoxime ( 13 ) derivatives depending upon both the reaction conditions and molar ratio employed. 2‐Thiazolyl‐2‐arylhydrazononitriles ( 7 ) and cyanoformazans ( 8 ) gave 1,2,3‐triazole derivatives ( 15 ) and ( 17 ) respectively upon treatment with hydroxylamine hydrochloride and concomitant loss of water molecule. Formation of novel 1,2,4‐triazin‐5(4H)‐one derivatives ( 21 ) has efficiently been carried out by treatment of amidoximes ( 18 ) with acetic anhydride in acetic acid.     

Ab initio conformational analysis of 1,5‐dithiacyclooctane, 1,5‐diselenacyclooctane,and 1,5‐ditelluracyclooctane

Energy‐minimum structures of 1,5‐dithiacyclooctane (1,5‐DTCO), 1,5‐diselenacyclooctane (1,5‐DSeCO), and 1,5‐ditelluracyclooctane (1,5‐DTeCO) were calculated by the ab initio molecular orbital method. Nine energy‐minimum structures were obtained for each compound. A twist‐boat–chair (TBC) structure is the most stable for 1,5‐DTCO and 1,5‐DSeCO, whereas a boat–boat (BB) structure is the most stable in 1,5‐DTeCO. The TBC conformer of 1,5‐DTCO has received little attention so far. The energy gap between HOMO and NHOMO in the TBC conformer of 1,5‐DTCO is in good agreement with the experimental data (photoelectron spectrum). For 1,5‐DTCO and 1,5‐DSeCO, the boat–chair (BC) conformer in which two chalcogen atoms face each other has the highest HOMO energy among the nine conformers, and the energy barriers between the TBC and BC conformers were calculated to be relatively low for these compounds. Therefore, a conformational change from the TBC to the BC is predicted to occur before these compounds are oxidized in solution. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 159–166, 1999     

Studies on enaminonitriles: A new synthesis of 1,3‐substituted pyrazole‐4‐carbonitrile

3‐Diethylaminoacrylonitrile ( 1 ) reacts with hydrazonyl halides ( 2a‐d ) to yield 1,3‐disubstituted pyrazole‐4‐carbonitriles 5a‐d. The acetyl 1‐p‐chlorophenylpyrazole‐4‐carbonitrile ( 5a ) condensed with hydrazine hydrate to yield the bishydrazone 10 and with dimethylformamide dimethylacetal to yield 1‐aryl‐3‐(3‐dimethylamino)acryloyl pyrazole‐4‐carbonitrile ( 11 ). This enamine reacts with hydrazine hydrate to yield the pyrazolylpyrazole ( 12 ) and with naphthoquinone to yield the 3‐naphthofuranoyl pyrazole 13. The pyra‐zolyl pyridine derivative 14 was obtained upon treatment of 11 with acetylacetone in the presence of ammonium acetate. Compound 11 was coupled with p‐chlorobenzene diazonium chloride to yield the hydrazone 16 that was coupled further with p‐chlorobenzenediazonium chloride to yield the formazane 18.     

Platinum‐Catalyzed Cascade Rearrangement Reaction of 1,5‐Diynyl Esters: Unusual Regioselective 1,5‐Hydride Migration

A highly regioselective sequential 1,3‐acyloxy migration/pentannulation/1,5‐hydride migration reaction is disclosed which provides an efficient access to (E)‐2‐vinyl‐3‐oxo‐1‐methyleneindenes under neutral and mild reaction conditions. The migrated hydrogen atom was derived from an unactivated alkyl group, and the long‐range 1,5‐H shift was confirmed through related deuterium experiments.     

Asymmetric Ruthenium‐Catalyzed Hydrogenation of 2,6‐Disubstituted 1,5‐Naphthyridines: Access to Chiral 1,5‐Diaza‐cis‐Decalins

The first asymmetric hydrogenation (AH) of 2,6‐disubstituted and 2,3,6‐trisubstituted 1,5‐naphthyridines, catalyzed by chiral cationic ruthenium diamine complexes, has been developed. A wide range of 1,5‐naphthyridine derivatives were efficiently hydrogenated to give 1,2,3,4‐tetrahydro‐1,5‐naphthyridines with up to 99 % ee and full conversions. This facile and green protocol is applicable to the scaled‐up synthesis of optically pure 1,5‐diaza‐cis‐decalins, which have been used as rigid chelating diamine ligands for asymmetric synthesis.     

Synthesis of new 3,3′‐(1,4‐phenylene)bis(1,5‐diones) derivatives

Several 3,3′‐(1,4‐phenylene)bis(1,5‐diones) and their chalcone precursors have been prepared in good to excellent yield via aldol addition and Michael addition starting from 3‐acetyl‐2,5‐dimethylfuran or 3‐acetyl‐2,5‐dimethyl‐thiophene with terephthalaldehyde in the presence of appropriate base NaOH or lithium diisopropylamide. The kind and amount of alkali played a critical role in improving the reaction rates and yields of the products. J. Heterocyclic Chem., (2011).     

An Expedient Method for the Synthesis of 1,2,4‐Triazolo‐fused 1,5‐Benzodiazepine, 1,5‐Benzoxazepine,and 1,5‐Benzothiazepine Scaffolds: A Novel Seven‐membered Ring System of Biological Interest

New heterocyclic compounds 1‐(3‐methyl‐9H‐dibenzo[b,f][1,2,4]triazolo[4,3‐d][1,4]diazepin‐6‐yl)ethanone 8a , 1‐(3‐methyldibenzo[b,f][1,2,4]triazolo[4,3‐d][1,4]oxazepin‐6‐yl)ethanone 8b , and 1‐(3‐methyldibenzo[b,f][1,2,4]triazolo[4,3‐d][1,4]thiazepin‐6‐yl)ethanone 8c are synthesized from benzodiazepinone, benzoxazepinone, and benzothiazepinone derivatives. These heterocyclic scaffolds have wide medicinal importance. Best results were obtained in antibacterial screening against Escherichia coli, Enterobacter cloacae, and Staphylococcus aureus and antifungal screening against Candida albicans and Fusarium oxysporum. 1,1‐Diphenyl‐2‐picrylhydrazyl radical scavenging activities of compounds 6c , 7c , and 8c were tested in doses 10, 20, 30, 40, and 50 μg/mL and were expressed as IC₅₀ values and percent of inhibition with means ± standard deviation of three different concentrations of synthesized compounds. The assignment of the structures of synthesized compounds was made by thin‐layer chromatography, elemental analysis, IR, ¹H‐NMR, ¹³C‐NMR, and liquid chromatography–mass spectrometry.     

Pentane‐1,5‐diaminium dibromide

The crystal structure of the title salt, C₅H₁₆N₂²⁺·2Br⁻, with Z = 12 and more unusually Z′ = 3, forms part of a small group of crystal structures in the Cambridge Structural Database that are ammonium bromide salts. One of the diaminium cation chains in the asymmetric unit exhibits positional disorder, which was modelled using a suitable disorder model. This compound also exhibits organic–inorganic layering in its packing arrangement that is typical of this class of compound. An extensive complex three‐dimensional hydrogen‐bonding network is also identified. The hydrogen bonds evident in this crystal structure were identified as being most likely strong charge‐assisted hydrogen bonds.