Synthesis and Properties of 1,3-Diaryl-5,6-dihydro-8H-imidazo[2,1-c]-1,4-oxazinium Bromides

It has been established that the condensation of 3-(4-methoxyphenylamino)-5,6-dihydro-2H-1,4-oxazine with substituted phenacyl bromides occurs at the exocyclic nitrogen atom with formation of 3-aryl-3-hydroxy-1-(4-methoxyphenyl)-2,5,6,8-tetrahydro-3H-imidazo[2,1-c]-1,4-oxazinium bromides. By treatment of the latter with acetic anhydride 3-aryl-1-(4-methoxyphenyl)-5,6-dihydro-8H-imidazo[2,1-c]-1,4-oxazinium bromides are formed. The structures of the compounds synthesized were determined via ¹H NMR spectroscopy and X-ray diffraction.     

Synthesis of 5H-imidazo[2,1-c]pyrrolo[1,2-a][1,4]benzodiazepine

We have synthesized 5H-imidazo[2,1-c]pyrrolo[1,2-a][1,4]benzodiazepine 1 in five steps from 1-(2-amino-methylphenyl) pyrrole 4 . Amidino derivatives 11-12 have also been prepared.     

The synthesis of 4H-imidazo[5,1-c][1,4]benzothiazine derivatives

A facile synthesis of the 4H-imidazo[5,1-c][1,4]benzothiazine ring system is described. The synthesis utilized the annulation of an imidazole ring onto a 2H-1,4-benzothiazin-3(4H)-one via the addition of the anion of ethyl isocyanoacetate. Methods for the functionalization of the 1-, 3-, 4-, and 5-positions of the ring system are presented.     

Synthesis of 5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepine and 10,11-dihydro-5H,12H-pyrrolo[2,1-c][1,4]benzodiazocine derivatives via cyclization of 2-aminomethylpyrroles

We have synthesized pyrrolo[1,2-α][1,4]benzodiazepine 6 and pyrrolo[2,1-c][1,4]benzodiazocines 12 and 13 from the corresponding 1-arylpyrrole 1d and 1-benzylpyrroles 7a and 7b by routes involving four and five steps, respectively.     

Synthesis of novel imidazo[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines and pyrimido[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines

Several 1 1-amino-5H-pyrrolo[2,1-c][1,4]benzodiazepines have been used as starting material to prepare a number of derivatives of 9H-imidazo[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines and 10H-pyrimido[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines. The imidazole nucleus was built by reaction of amidines with ethyl bromopyruvate or aminoacetaldehyde dimethylacetal. Several derivatives of imidazo[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepine have been prepared by formylation of the pyrrole ring followed by formation of thioamides. Condensation of 11-amino-5H-pyrrolo[2,1-c][1,4]benzodiazepines with diethyl ethoxymethylenemalonate afforded intermediate diesters which were transformed into the corresponding 10H-pyrimido[1,2-a]pyrrolo[2,1-c]-benzodiazepines.     

Synthesis of 5,6-dihydro-4H-pyrrolo[1,2-a]thieno[2,3-f][1,4]diazepines

The reduction of 1-[3-(thienyl-2-carbonitrile)]pyrrole, formed by condensation of 3-aminothiophene-2-carbonitrile with 2,5-dimethoxytetrahydrofuran, gave 1-[3-(thienyl-2-aminomethyl)]pyrrole. This compound was found to be a convenient intermediate for the preparation of 4-aryl-5,6-dihydro-4H-pyrrolo[1,2-a]thieno-[2,3-f][1,4]diazepines which was accomplished by two different synthetic routes.     

Novel heterocycles. 9. Synthesis of the benzofuro[2,3-c][1,2]thiazine ring system

The treatment of 2-coumaranone with the Vilsmeier reagent affords three products: 2-chloro-3-benzofurancarboxaldehyde ( 3 ), 3-dimethylaminomethylene-2-(3H)benzofuranone ( 4 ), and 3-dimethylaminomethylene-2,3-dihydro-2-oxo-6-benzofurancarboxaldehyde ( 5 ). Both 4 and 5 are isolated as a mixture of E and Z isomers. The reaction of 3 with the anion of N-methylmethanesulfonamide affords the title compound 1-methyl-1H-benzofuro[2,3-c][1,2]-thiazine 2,2-dioxide ( 6 ). Spectral data is also discussed.     

First synthesis of 5,6-dihydro-4H-furo[3,2-f]pyrrolo- [1,2-a][1,4]diazepines

The synthetic pathway leading to 5,6-dihydro-4H-furo[3,2-f]pyrrolo[1,2-a][1,4]diazepines is described in four steps starting from α-bromophenones via 2-amino-3-furonitriles.     

Five-membered 2,3-dioxo heterocycles: CI. Reaction of 3-aroylpyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones with arylhydrazines. Crystal and molecular structure of substituted 2-hydrazonopyrrolo[2,1-c][1,4]benzoxazine

A new direction of nucleophilic attack was revealed in the reactions of 3-aroylpyrrolo[2,1-c][1,4]-benzoxazine-1,2,4-triones with o-tolylhydrazine and 2-hydrazinylbenzoic acid hydrochloride, which afforded the corresponding hydrazones at the C²=O carbonyl group, substituted 2-(2-o-tolylhydrazono)pyrrolo[2,1-c]-[1,4]benzoxazine-1,4(2H)-diones and pyrrolo[2,1-c][1,4]benzoxazin-2(4H)-ylidenehydrazinylbenzoic acids. The structure of (Z)-2-{2-[3-benzoyl-1,4-dioxo-1H-pyrrolo[2,1-c][1,4]benzoxazin-2(4H)-ylidene]hydrazinyl}-benzoic acid was determined by X-ray analysis.     

Synthesis of Sequence-Selective C8-Linked Pyrrolo[2,1-c][1,4]benzodiazepine DNA Interstrand Cross-Linking Agents

An efficient convergent synthesis of a homologous series of C8-linked pyrrolobenzodiazepine dimers with remarkable DNA interstrand cross-linking activity and potent in vitro cytotoxicity is reported. The "amino thioacetal" cyclization procedure was used to produce the electrophilic DNA-interactive N10-C11 imine moiety during the final synthetic step. In order to construct the key A-ring fragments (9a-d), a versatile convergent approach has been developed to join two units of vanillic acid with alpha,omega-dihaloalkanes of varying length to provide the required bis(4-carboxy-2-methoxyphenoxy)alkanes while avoiding the formation of mixtures of monoalkylated and bisalkylated products.     

A facile synthesis and structure determination from 13c-nmr spectroscopy of a novel heterocycle 1,1′-ethylenebis[2,3,8,8a-tetrahydro-5,8a-dimethyl-1H-imidazo[2,1-c][1,4]thiazine], a case of transannular stabilization

The condensation of 4-thiaheptane-2,6-dione with triethylenetetramine does not produce the macrocycle 1-thia-3,14-dimethyl-4,7,10-13-tetrazacyclopentadeca-3,13-diene; instead two molecules of the dione condense with one of the amine to give the title compound.     

Novel synthesis of spirocyclic-3,4-dihydro-2H-benzo[b][1,4]oxazine derivatives

A two-step procedure involving acid catalyzed ring opening of spirocyclic epoxides with 2-haloanilines and subsequent palladium-catalyzed intramolecular C–O bond formation to provide spirocyclic-3,4-dihydro-2H-benzo[b][1,4]oxazine derivatives is described.     

Kinetics of Addition of Alcohols to 3-Aroyl-2,4-dihydro-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones

The kinetics of the reaction of 3-aroyl-2,4-dihydro-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones with aliphatic alcohols in toluene at 25°C were studied by spectrophotometry. The effects of electronic and steric factors in the nucleophile and substrate were estimated by treatment of the kinetic results by the Hammett and Taft equations.     

Synthesis of novel imidazo[1,2-a][3,1]benzothiazines 4, imidazo[1,2-a]-[1,2,4]benzotriazines 5, and 4H-imidazo[2,3-c]pyrido[2,3-e][1,4]oxazines 6

Starting from the readily available 2-aminobenzhydrols ( 7 ), 3-amino-1,2,4-benzotriazine ( 11 ) and 2-amino-3-pyridinol ( 12 ), novel derivatives of 5-phenyl-5H-imidazo[1,2-a][3,1]benzothiazine-2-carboxylic acid, ethyl ester ( 4 ), imidazo[2,1-c][1,2,4]benzotriazine-2-carboxylic acid, ethyl ester ( 5 ) and 4H-imidazo[2,3-c]pyrido-[2,3-e][1,4]oxazine ( 6 ) were prepared.     

Pyrrolo[1,4]benzodiazepines. III. synthesis of 5,11-dioxo-1,10,11,11a-tetrahydro-2-vinyl-5H-pyrrolo[2,1-c][1,4]benzodiazepine

Some pyrrolo[2,1-c][1,4]benzodiazepines having a chain of two carbon atoms, as it is found in antibiotic tomaymycin, were prepared. The first reaction was the C-acetylation of 1-(2-nitrobenzoyl)-Δ⁴-pyrroline-2,2-dicarboxylic acid diethyl ester; successive transformations of the acetyl group and cyclization gave the proposed structures.     

Synthesis and Photochromism of Novel Spiro(indoline-2,3'-naphtho[2,1-b][1,4]oxazine)

A series of novel spirooxazine(SPO) derivatives containing nitrogen heterocycles was synthesized and characterized by ¹H NMR spectra, Fourier transform infrared(FTIR) spectra, mass spectra(MS) and elemental analysis, and their photochromic behaviors were fully investigated in solvents and polymer media. In solvents, they displayed excellent photochromism properties such as high photochromic response and fast thermal bleaching rate. Especially, compounds 1 and 4 exhibited strong fluorescence intensities in dichloromethane solution. It was additionally found that compound 4 showed high fatigue resistence in poly(methyl methacrylate)(PMMA) film, and the thermal decay curves were fitted with biexponential function in PMMA film.