Synthesis of fluorosubstituted 10,11-dihydrodibenz[b,f][1,4]oxazepines

The synthesis of a series of polyfluorinated derivatives of 10,11-dihydrodibenz[b,f][1,4]oxazepine and dibenz[b,f][1,4]oxazepine-11(10 H)-one has been effected.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1679–1682, December, 1990.     

Phase transfer catalysis in N-alkylations of the pharmaceutical intermediates 5H-dibenz[b,f]azepine and 5H-10,11-dihydrodibenz[b,f]azepine

The two title compounds were alkylated under very mild phase-transfer-catalysis conditions. Differences in reactivities of the two heterocyclic nucleophiles, and in the reactivities of various alkyl halides are discussed.     

Synthesis and properties of some tetracyclic derivatives of 9H-carbazole, 10,11-dihydro-5H-dibenz[b,f]azepine,and 5,11-dihydrodibenz[b,e] [1,4]oxazepine

The behavior of 5,6-dihydro-4H-pyrido[3,2,1-jk]carbazol-4-one (10) , 1,2,7,8-tetrahydro-3H-quino[1,8-ab][1]benzazepin-3-one (11) , 1,2-dihydro-9H-[1]benzazepino[1,9-ab] [4,1]benzoxazepin-4 (3H)one (13) , and 1,2-dihydro-8H-[1]benzazepino[1,9-cd] [1,5]benzoxazepin-4(3H)one (14) towards the Schmidt reaction has been determined in polyphosphoric acid and in benzeneor chloroform-sulfuric acid. Evidence for the structure of the new heterocyclic systems obtained from these four compounds is presented.     

Nucleophilic replacement of fluorine in tetrafluorodibenz[b,f]-[1,4] oxazepines

Tetrafluorodibenz[b,f][1,4]oxazepines react with piperidine, ammonia, and sodium methoxide with replacement of the fluorine atom in the para-position to the azomethine group.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 668–671, May, 1989.     

Electrophilic substitution of dibenz[b,f]oxepin

Dibenz[b,f]oxepin undergoes nitration and acid-catalyzed deuteration at the 10-position and adds bromine across the 10,11 bond. These reactions contradict predictions made by the SCFMO method. Chemical reactions and NMR spectroscopy suggest that dibenz[b,f]oxepin is only weakly aromatic.     

Nucleophilic substitution in dibenz[b,d]iodolium and 11,12-dihydro-10H-dibenz[b,g]iodocinium cations

Treatment of dibenz[b,d]iodolium tetrafluoroborate with NO₂ ^–, Br^–, and N₃ ^– ions gave, along with nucleophilic substitution products, 2-nitro-, 2-bromo-, and 2-azido-2-iodiphenyls, diphenyl, 2-iododiphenyl, and 2,2-diiododiphenyl (products of one electron reduction), whereas 11,12-dihydro-10H-dibenz[b,g]iodocinium tetrafluoroborate underwent nucleophilic substitution with all three nucleophiles to give a single product in each case: 1-(2-nitrophenyl)-, 1-(2-bromophenyl)-, or 1-(2-azidophenyl)-3-(2-iodophenyl)propane.M. V. Lomonosov Moscow State University, Moscow 119899. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 405–412, March, 1998.     

Synthesis and chemistry of enantiomerically pure 10,11-dihydrodibenzo[b,f]thiepines

Several chiral thiepines were efficiently constructed using sulfur diimidazole in combination with a variety of bislithiated carbon fragments. The sulfur atom in these thiepines is found to be unusually unreactive compared to diphenylsulfide.     

Metallations of 5 H-dibenz [b,f] azepine and 10,11-dihydro-5H-dibenz [b,f] azepine. Synthesis of 4-substituted derivatives

The synthesis of 4-substituted 5 H-dibenz [b, f] azepines and 10, 11-dihydro-5 H-dibenz [b, f] azepine resulting from the reaction of the corresponding 4, 5-dilithio derivatives and different N, N-dimethylamides is reported. The total assignment of the pmr spectra of the prepared formyl derivatives based on decoupling experiments is also described.     

SYNTHESIS,REACTIVITY AND CONFORMATION OF 10,11-DIHYDRODIBENZO-[b,f]PHOSPHEPIN AND DIBENZO[b,f]PHOSPHEPIN DERIVATIVES. PHOSPHORUS ANALOGUES OF IMINOBIBENZYL ANTIDEPRESSANTS

Abstract

Derivatives of the novel dibenzo[b,f]phosphepin system are prepared from 10,11-dihydro-5-phenyl-5H-bibenzo[b,f]phosphepin 5-oxide (2). New members in the 10,11-dihydro-5H-dibenzo[b,f]phosphepin series, including phosphorus analogues (7, 10) of the andidepressant drug imipramine (30), are also reported. Products of nucleophilic substitution at tetrahedral phosphorus in 2 appear to be determined by the relative apicophilicity of the nucleophile. Conformational analysis based on ¹H NMR data suggests folded (“butterfly”) conformation for the tricyclic compounds. The twisted boat conformation of the central ring in the 10,11-dihydro compounds bears a pseudo-equatorial P[dbnd]O oxygen or a P[dbnd]S sulfur, in solution. Symmetric AA‘BB’ spin systems are found in 4,5 and 7, and their solution conformations appear to be similar to those of analogous 10,11-dihydrodibenzo[b,f]azepine derivatives. The interaction of some compounds with NMR shift reagents and their mass spectral fragmentations are discussed.     

The assignment of the 1H-NMR and 13C-NMR spectra of 5H-dibenz[b,f]azepine and 10,11-dihydro-5H-dibenz[b,f]azepine

The total assignments of the ¹H-nmr and ¹³C-nmr spectra of 5H-dibenz[b,f]azepine [1] and 10,11-dihydro-5H-dibenz[b,f]azepine ( 2 ) have been made based on comparison with the corresponding 4,6-dideuterated derivatives 3 , and 4 . These compounds were prepared via repeated lithiations and subsequent deuterations of 1 and 2 .     

Synthesis of trans-10,11-Dihydro-10,11-dihydroxy-5H-dibenz[b,f]azepine-5-carboxamide,a Major Metabolite of Carbamazepine

The stereoselectivity of the reduction of 5-carbamoyl-10,11-dihydro-11-oxo-5H-dibenz[b,f]azepine-10-yl acetate ( 6 ), prepared in two steps from 10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide ( 4 ), has been studied. Among the reagents used, diisobutylaluminum hydride (DIBAH) was found to give the highest trans/cis diol ratio. This allowed the preparation of the important trans-diol metabolite 3 of carbamazepine ( 1 ).     

Conformational studies of 5-acetyl-10-cyano-10,11-dihydro-5H-dibenz[b,f]azepine

5 - Acetyl - 10 - cyano - 10,11 - dihydro - 5H - dibenz[b,f]azepine, 3, has been synthesized and its conformations in solution have been studied by variable temperature NMR. At ?55° in CDCl₃ solution, 3 shows the signals due to four different conformational isomers. At 55°, signals due to only two conformers can be seen. The ABX pattern of each of the four conformers was analyzed using double resonance experiments and the LAOCN3 computer program. The relative abundances of the isomers in the mixtures were estimated by computer additions of different proportions of the spectra calculated for the separate isomers. These spectral observations are discussed in detail and interpreted in terms of slow inversion of the seven-membered ring by torsion of the 4a55a bonds and restricted twisting of the C10C11 ethylene bridge.     

Neurotrope und psychotrope Substanzen, 5. Mitt.: Synthese neuer Aminoderivate von 10,11-Dihydrodibenzo-[a,d]cyclohepten und 10,11-Dihydrodibenzo[b,f]thiepin

Zusammenfassung Im Rahmen der Suche nach neuen neurotropen und psychotropen Substanzen, besonders nach antidepressiv wirkenden Psychopharmaka, wurde eine systematische präparative Arbeit in den Gruppen der 10-substituierten Derivate des 10,11-Dihydrodibenzo[a,d]cycloheptens (I) und des 10,11-Dihydrodibenzo[b,f]-thiepins (II) unternommen. Im ersten Fall war die Ausgangssubstanz das Keton XIV, das mit üblichen Methoden zum basischen Äther XVI, zu Aminen und Derivaten XVIII–XXII und schließlich in dieMannich-Base XXVI übergeführt wurde. DieBeckmannsche Umlagerung des Oxims XVII eröffnete den Weg zu Derivaten eines neuen Systems, des 5,6,7,12-Tetrahydrodibenz[b,e]azocins (Verbindungen XXVIII, XXX und XXXI). Auch im zweiten Fall bildete das entsprechende Keton (XXXVIII) die Schlüsselsubstanz, die einerseits zu Aminen mit der Aminogruppe in der Seitenkette (XXXIX, XL, XLII, LV, LVI), anderseits zu Aminen mit der direkt am Skelett haftenden Aminogruppe (XLIV–LIII) umgesetzt wurde. Außer den angeführten Aminen wurde in allen drei Gruppen eine Reihe von neutralen Verbindungen hergestellt (Zwischenprodukte und Nebenprodukte), deren Struktur meistens mit Hilfe der Spektren geklärt wurde. Die vorläufigen Ergebnisse der pharmakologischen Prüfung einiger Produkte deuten interessante Wirksamkeit an, besonders vom Standpunkt der erwarteten neurotropen und psychotropen Eigenschaften aus.

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In the effort to find new neurotropic and psychotropic substances a systematic chemical study was undertaken in the groups of the 10-substituted derivatives of 10,11-dihydrodibenzo[a,d]-cycloheptene (I) and 10,11-dihydrodibenzo[b,f]thiepine (II). In the first case the ketone XIV was transformed by usual methods into the basic ether XVI, to the amines and derivatives XVIII–XXII, and to theMannich base XXVI. TheBeckmann rearrangement of the oxime XVII opened the way to derivatives of a new system — 5,6,7,12-tetrahydrodibenz[b,e]azocine (compounds XXVIII, XXX and XXXI). In the second case (derivatives of II) the syntheses started from the ketone XXXVIII and two series of amines were prepared: with the amino group in the side chain (XXXIX, XL, XLII, LV, LVI) and with the amino group attached directly to the skeleton (XLIV–LIII). In addition to the amines several neutral compounds in either group were synthesized (intermediates and byproducts), the structure of which was elucidated mainly by means of the spectra. Preliminary results of the pharmacological testing show a rather important degree of activity of some substances, especially in the line of the expected neurotropic and psychotropic properties.

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mit technischer Hilfe von

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Herrn Professor Dr.Hermann Bretschneider zum 60. Geburtstag gewidmet

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4. Mitt.:J. O. Jílek, K. Pelz, D. Pavlíková undM. Protiva, Coll. Czechoslov. Chem. Commun.30, im Druck (1965).     

Nucleophilic substitution of alkylchlorodihydro[60]fullerenes: thermodynamic stabilities of alkylated C60 cation intermediates

Thermodynamic stabilities of alkylated C60 cations (RC60+) were determined based on the activation free energies of SN1 solvolysis of the title compounds, indicating that these cations have stabilities comparable to that of the tert-butyl cation.     

Nucleophilic addition to benzo[b]thieno[2,3-b]benzo[b]thiophene S,S,S′,S′-tetroxide

The reaction of benzo[b]thieno[2,3-b]benzo[b]thiophene S,S,S′,S′-tetroxide with primary and secondary amines and with alcohols gave 10 b-amino- and 10 b-alkoxy-5a, 10b-dihydro-benzo[b]thieno[2,3-b]benzo[b]thiophene S,S,S′,S′-tetroxides. These nucleophilic reagents do not add to benzo[b]thieno[2,3-b]benzo[b]thiophene S,S-dioxide.