A general route to the synthesis of 1,5-methano- and 1,5-ethano- 2,3,4,5-tetrahydro-1H-3-benzazepines

A general approach to preparing 1,5-methano- (1) and 1,5-ethano-2,3,4,5-tetrahydro-1H-3-benzazepine (2) is discussed. This strategy involves converting an indanone or tetralone (4) to a cyanohydrin (3) which is subjected to hydrogenolysis followed by lactamization and reduction to provide bicyclic aryl piperidine (1) and bicyclic aryl homopiperidine (2).     

2,3,4,5-四氢-1,5-甲桥-1H-3-苯并氮杂(艹卓)的合成

以1,4-二氢-1,4-甲桥萘为起始原料,经臭氧化、还原性胺化及还原反应合成了新型戒烟药伐仑克林的重要中间体2,3,4,5-四氢-1,5-甲桥-1H-3-苯并氮杂(艹卓),其结构经1H NMR和MS确证.     

Synthesis and dynamic stereochemistry of 1,5-disubstituted 2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-2-ones

The 1-isopropyl and 1-benzyl derivatives of 1,5-tetrahydrobenzodiazepin-2-one were synthesized by alkylation under the conditions of phase-transfer catalysis. The inversion of the heterocycle was studied by PMR spectroscopy, and the free energies of activation were determined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 254–258, February, 1986.     

Synthesis of 3-alkyl-8-substituted- and 4-hydroxy-8-substituted-2,3,4,5-tetrahydro-1H-2-benzazepines

Based on the Schmidt reaction and an iodolactone ring expansion reaction, two different synthetic routes to substituted 2,3,4,5-tetrahydro-1H-2-benzazepines were developed. The Schmidt reaction on 2,3-dihydro-2H-1-naphthalenone ( 1 ) gave 3 , the product resulting from the alkyl group migration, as the major product instead of the tetrazole 2. This prompted the investigation of the Schmidt reaction on aromatic ketones 8 and 12. The product 9 due to alkyl group migration was the major product of the Schmidt reaction on 2-methyl-3,4-dihydro-2H-1-naphthalenone ( 8 ). The β-keto diester 12 gave a mixture of decarb-oxylated lactams after the Schmidt reaction. In this case, the lactam 13 resulting from the migration of the aromatic ring dominated over the other lactam 14. When lactam 14 was subjected to nitration, a single regioisomer was produced and transformed to the bromo alcohol 19. The other approach was based on the single pot ring expansion of the iodolactone 22 to the lactam 23 in the presence of methanolic ammonia. The iodolactone 22 was readily prepared from 2-allylbenzoic acid.     

Two general routes to 1,4-disubstituted-2,3,4,5-tetrahydro- 1H-3-benzazepines

[structure] Two general routes to 1,4-disubstituted-2,3,4, 5-tetrahydro-1H-3-benzazepines are described. Both routes utilize an appropriately functionalized phenethylamino alcohol as the penultimate intermediate: the first route makes use of the reductive amination of a benzyl alkyl ketone with alpha-(aminomethyl)benzyl alcohol, while the second route utilizes the addition of a Grignard reagent to the oxazolidine derived from a substitued phenylacetaldehyde and alpha-(methylaminomethyl)benzyl alcohol. In all cases studied, the cis-1,4-disubstituted-2,3,4, 5-tetrahydro-1H-3-benzazepine was obtained as the major product.     

Synthesis of nitro-substituted 4-methyl-2,3-dihydro- and 2,3,4,5-tetrahydro-1H-1,5-benzo-2-diazepinones

The nitration of 4-methyl-2,3-dihydro-1H-1,5-benzo-2-diazepinone gives the 7 nitro derivative. The 8-nitro isomer was obtained from 4-nitro-1,2-phenylenediamine. The catalytic hydrogenation of the nitrobenzodiazepinones gives the 7- and 8-amino derivatives. The nitrobenzodiazepinones exist in the enol form in alkaline media.     

The synthesis of some 7- and 7,8-substituted 2,3,4,5-tetrahydro-1H-3-benzazepines

The nitration of 2,3,4,5-tetrahydro-1H-3-benzazepine and its 3-methyl and 3-acetyl derivatives yields the corresponding 7-nitro derivatives which can be further transformed by classical procedures. The preparation of the ether cleavage products of the known 2,3,4,5-tetrahydro-7,8-dimethoxy-1H-3-benzazepine is also reported.     

A novel synthesis of aromatic methoxy and methylenedioxy substituted 2,3,4,5-tetrahydro-1H-3-benzazepines

A new synthesis of aromatic methoxy and methylenedioxy substituted 2,3,4,5-tetrahydro-1H-3-benzazepines is described. Suitably substituted phenethylamines and their α-methyl homologs in the form of their N-acetyl derivatives are chloromethylated, the resulting benzyl chlorides are reacted with cyanide and hydrolysis of the latter yields 2-(2-aminoethyl)phenylacetic acid derivatives. Thermal cyclization yields the corresponding lactams. Hydride reduction of these lactams furnishes the substituted 2,3,4,5-tetrahydro-1H-3-benzazepines which may be methylated on nitrogen by formaldehyde and hydrogen. By this sequence a number of previously unde-scribed compounds have been prepared.     

Syntheses of the opioid substructures 1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocine and 2,3,4,5-tetrahydro-1,5-methano-1H-2-benzazepine

Concise syntheses of 1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocine (12) and 2,3,4,5-tetrahydro-1,5-methano-1H-2-benzazepine (18) are described and involve an intramolecular Friedel-Crafts alkylation and an intramolecular Heck cyclization as their respective key ring-forming steps.     

Preparation of 1,5-methano-2,3,4,5- tetrahydro-1H-3-benzazepine via Pd-catalyzed cyclization

[reaction: see text] A new approach to prepare 1,5-methano-2,3,4,5-tetrahydro-1H-3-benzanepine (1) is discussed. This strategy utilized a tandem Michael addition and Pd-catalyzed cyclization to afford cyanobenzofulvene acetal 13. This indene intermediate (13) was subjected to hydrogenolysis to provide an amino ester (12) and was cyclized with base to afford lactam 5. The lactam (5) was reduced with borane to afford the desired benzazepine (1).     

An efficient three-component one-pot approach to the synthesis of 2,3,4,5-tetrahydro-1H-2-benzazepines by means of rhodium-catalyzed hydroaminomethylation

We have developed a novel and efficient three-component one-pot, catalytic approach for the synthesis of 2,3,4,5-tetrahydro-1H-2-benzazepines, using a rhodium catalyst that does not require phosphine. The isolated yields are excellent and the protocol tolerates anilines of diverse basicity.     

Synthesis of 2-substituted 1-benzyl-2,3,4,5-tetrahydro-1-benzazepines by palladium catalysis. Observation of a competitive β-hydride elimination pathway

A synthetic route to 1-benzyl-tetrahydro-1-benzazepine is reported, which also permits access to analogous structures with alkyl and aryl substituents at position-2 of the aliphatic ring. Palladium catalysis is utilized in two of the three steps, constructing the seven-membered rings effectively from 2-bromoiodobenzene. Competitive β-hydride elimination was observed in the attempted carbonnitrogen bond formation with a sterically bulky substrate (when R=tert-butyl).     

Substituted 2,3,4,5-tetrahydro-1H-3-benzazepine and 2,3,4,5-tetrahydro-1H-naphth[1,2-d] azepine derivatives

The multi-step synthetic procedures to prepare a number of 2,3,4,5-tetrahydro-1H-benzazepine derivatives 1 through a series of intermediates are described. The condensation of arylaldehydes 2 with 2-nitropropanes 3 gave nitroalcohols 4 which were reduced to alcohol amines 5 . The condensation of 5 with arylacetaldehydes 6 gave imino derivatives 7 which on reduction with borohydride gave secondary amines 8 . By employing different methods, alcohol amines 5 were condensed with arylacetic acids 9 to give amides 10 which were then reduced to amines 8 . On treatment with mineral acids, amines 8 were cyclized to the target compounds 1 . Biological activities of 1 are also briefly discussed.     

Synthesis and study of structure of 5-formyl-substituted 2,3,4,5-tetrahydro-1H-1, 5-benzodiazepin-2-ones

A series of 5-formyl derivatives was synthesized by formylation of 2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-2-ones with a mixture of formic acid and acetic anhydride. The structure of their rotation isomers was studied by PMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 957–961, July, 1988.     

A 13C-NMR assignment study of a series of 2,3,4,5-tetrahydro-1-methyl-1H-1,5-benzodiazepine-2,4-diones

The natural abundance ¹³C-nmr spectra of a series of 2,3,4,5-tetrahydro-1-methyl-1H-1,5-benzodiazepine-2,4-diones have been recorded: two of these compounds, clobazam and triflubazam, are clinically used as psychotherapeutic agents. The assignments of the various resonances have been made by chemical shift arguments, by the analysis of the fine splittings caused by one bond and long range couplings, and also by comparison with model compounds.     

Complete 1H and 13C NMR spectral assignment of N-aralkylsulfonamides, N-sulfonyl-1,2,3,4-tetrahydroisoquinolines and N-sulfonyl-2,3,4,5-tetrahydro-1H-2-benzazepines. Conformational analysis of N-[((3',4'-dichlorophenyl)methyl)sulfonyl]-3-methyl-2,3,4,5-tetrahydro-1H-2-benzazepin

The complete and unambiguous assignment of the 1H NMR and 13C NMR spectra of 26 N-aralkylsulfonamides, N-sulfonyl-1,2,3,4-tetrahydroisoquinolines and N-sulfonylbenz[c]azepines was performed on the basis of APT, DEPT, homonuclear (gs-COSY) and 1H-detected heteronuclear one-bond (gs-HMQC) and long-range (gs-HMBC) correlation experiments. The methylated 2,3,4,5-tetrahydro-1H-2-benzazepine derivative 26 adopts a chair conformation as determined by 1H-1H coupling analysis and gamma-gauche effects. This is supported by a single-crystal X-ray structure analysis.