Synthesis of Tetrahydrobenzazepinesulfonamides and Their Rearrangement to Diarylsulfones

A new class of diarylsulfones, in which tetrahydrobenzazepine comprises one of the aromatic moieties, has been synthesized via the acid‐catalyzed rearrangement of several substituted benzazepinesulfonamides. The rearrangement is normally ortho but in at least one case a para isomer is also formed. Sulfones of this type have been shown to possess potent anti‐HIV activity.     

A practical and efficient synthesis of 6-carboalkoxy-13-cycloalkyl-5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid derivatives

A convenient and practical synthesis of 6-carboalkoxy-13-cycloalkyl-5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid derivatives (6) has been developed. The key step in the synthesis utilizes an intramolecular tandem reaction sequence of a Michael addition followed by a Horner–Wadsworth–Emmons (HWE) olefination reaction between hemi-aminal 11 and methyl 2-(dimethoxyphosphoryl)acrylate 12. The ring construction occurred efficiently and purification of the products 6 was straightforward. The C-10 methyl ester of 6a was hydrolyzed selectively to the carboxylic acid 13 while the olefin of 6d was converted to the cyclopropane 14 using trimethylsulfoxonium iodide in DMSO in the presence of NaH.     

Four related benzazepine derivatives in a reaction pathway leading to a benzazepine carboxylic acid: hydrogen‐bonded assembly in zero,one, two and three dimensions

(2R*,4S*)‐Methyl 2,3,4,5‐tetrahydro‐1,4‐epoxy‐1H‐benz[b]azepine‐2‐carboxylate, C₁₂H₁₃NO₃, (I), and its reduction product (2R*,4S*)‐methyl 4‐hydroxy‐2,3,4,5‐tetrahydro‐1H‐benz[b]azepine‐2‐carboxylate, C₁₂H₁₅NO₃, (II), both crystallize as single enantiomers in the space group P2₁2₁2₁, while the hydrolysis product (2RS,4SR)‐4‐hydroxy‐2,3,4,5‐tetrahydro‐1H‐benz[b]azepine‐2‐carboxylic acid, C₁₁H₁₃NO₃, (III), and the lactone (2RS,5SR)‐8‐(trifluoromethoxy)‐5,6‐dihydro‐1H‐2,5‐methanobenz[e][1,4]oxazocin‐3(2H)‐one, C₁₂H₁₀F₃NO₃, (IV), both crystallize as racemic mixtures in the space group P2₁/c. The molecules of compound (IV) are linked into centrosymmetric R₂²(10) dimers by N—H...O hydrogen bonds, and those of compound (I) are linked into chains by C—H...π(arene) hydrogen bonds. A combination of O—H...O and O—H...N hydrogen bonds links the molecules of compound (III) into sheets containing equal numbers of R₄⁴(14) and R₄⁴(26) rings, and a combination of C—H...π(arene) hydrogen bonds and three‐centre O—H...(N,O) hydrogen bonds links the molecules of compound (II) into a three‐dimensional framework structure. Comparisons are made with some related compounds.     

An Efficient Approach for the Construction of Benzazepine and Benzoxepine Derivatives

A novel and facile synthetic protocol for the construction of benzazepine and benzoxepine derivatives through a copper(I)‐catalyzed reaction of 2‐(2‐ethynylphenyl)‐1‐tosylaziridine or 2‐(2‐ethynylphenyl)oxirane with sulfonyl azides is disclosed. A ketenimine is the key intermediate during the reaction process.     

新型三环系稠杂环［1,2,4］-三唑并［1,5-a］［1］-苯并氮杂及［1,2,4］-三唑并［1,5-a］-喹啉的合成

α-四氢萘酮的乙氧羰基腙(1)经LTA氧化, 得到α-偶氮-α-乙酰氧基化合物2. 在AlCl3作用下, 化合物2脱去乙酰氧基产生重氮正离子中间体3, 再经与腈的1,3-偶极环加成、 ［1,2］-迁移扩环、 碱性水解和与苦味酸作用, 得到新型［1,2,4］-三唑并［1,5 a］［1］苯并氮杂苦味酸盐6a~6c. 以2,3-二氢-1-茚酮为底物, 采用相同的合成路线, 合成了1,2,4-三唑并［1,5-a］-二氢喹啉苦味酸盐12a~12c.     

FeCl3·6H2O-promoted skeleton-rearrangement of 1-substituted-3-benzazepines: substrate extension and product utilization

FeCl₃·6H₂O-promoted skeleton-rearrangement of 1-substituted-3-benzazepines was further exploited. Both 1-aryl- and 1-alkyl- or 1-alkenyl-benzazepines underwent this reaction smoothly. The rearrangement products were used to prepare a series of novel derivatives containing both tetrahydroisoquinoline (THIQ) and tetrahydropyrimidin-4(1H)-one scaffolds through a Mannich-type process.     

Galanthamine analogs: 6H-benzofuro[3a,3,2,-e,f][1]benzazepine and 6H-benzofuro[3a,3,2-e,f][3]benzazepine

The known cholinesterase inhibitory capability of the Amarylidaceae alkaloid galanthamine prompted preparation of analogs in which the position of the nitrogen within the azepine ring is altered. The analogs 6H-benzofuro[3a,3,2-e,f][1]benzazepine and 6H-benzofuro[3a,3,2-e,f][3]benzazepine were prepared in 19 and 2.5%, respectively, following Kametani and Shimizu approaches, respectively. The aniline derivative 6H-benzofuro[3a,3,2-e,f][1]benzazepine failed to undergo most of the reactions typical for galanthamine. Thus, it neither oxidized to the analogous narwedine, nor epimerized to the analogous epigalanthamine, nor reduced to the lycoramine analog, under the conditions used for galanthamine.     

Synthesis and properties of new functionalized 2-benzazepines

2-Aryl-4-hydroxy-2,3-dihydro-1H-2-benzazepine-5-carbonitriles were obtained by the cyclization of methyl esters of N-aryl-N-(2-cyanomethylbenzyl)aminoacetic acids by the action of sodium methylate. The keto—enol tautomerism of these compounds and their reactions with hydrazines were studied. Previous communication, see ref. [1]. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1026–1031, July, 2006.     

High‐performance liquid chromatographic and subcritical fluid chromatographic separation of α‐arylated ß‐carboline,N‐alkylated tetrahydroisoquinolines and their bioisosteres on polysaccharide‐based chiral stationary phases

New, pharmacologically interesting chiral amino compounds, namely, stereoisomers of α‐hydroxynaphthyl‐ß‐carboline, benz[d]azepine and benz[c]azepine analogs as well as N‐α‐hydroxynaphthylbenzyl‐substituted isoquinolines were enantioseparated by high‐performance liquid chromatographic and subcritical fluid chromatographic methods on polysaccharide‐based chiral stationary phases. Separation of the stereoisomers was optimized in both subcritical fluid chromatography and normal phase liquid chromatographic modes by investigating the effects of the composition of the bulk solvent, temperature, and the structures of the analytes and selectors. Both normal phase liquid chromatography and subcritical fluid chromatography exhibited satisfactory performance, albeit with somewhat different effectiveness in the separation of the stereoisomers studied. The optimized methods offer the possibility to apply preparative‐scale separations thereby enabling further pharmacological investigations of the enantiomers.