5//-Benz azepine Compound

Treatment of the /-butyl formamidine (72) with /-butyllithium followed by an electrophile produces the tetrahydroazepine derivatives (73) <85JOC10I9>. Typical electrophiles are n-propyl iodide, trimethylsilyl chloride, and benzyl bromide. 2,3,4,6-tetrahydro-17/-benz((>]azepines <93JOC6538> afford the corresponding 2-alkyl-dihydro derivatives together with the product from o-alkylation in the aromatic ring. iV-Boc derivatives give an even better yield of the 2-alkyl derivative, which is in marked contrast to the five- and six-membered compounds, where the sole product from the iV-Boc... 

A detailed study of the dehydrogenation of 10.1 l-dihydro-5//-benz[6,/]azcpinc (47) over metal oxides at 550 C revealed that cobalt(II) oxide, iron(III) oxide and manganese(III) oxide are effective catalysts (yields 30-40%), but formation of 5//-dibenz[7),/]azepinc (48) is accompanied by ring contraction of the dihydro compound to 9-methylacridine and acridine in 3-20 % yield.111 In contrast, tin(IV) oxide, zinc(II) oxide. chromium(III) oxide, cerium(IV) oxide and magnesium oxide arc less-effective catalysts (7-14% yield) but provide pure 5H-dibenz[b,/]azepine. On the basis of these results, optimum conditions (83 88% selectivity 94-98 % yield) for the formation of the dibenzazepine are proposed which employ a K2CO,/ Mn203/Sn02/Mg0 catalyst (1 7 3 10) at 550 C. 

Examples of electrophilic substitution (other than protonation) at the heterocyclic ring of benz- and dibenz-azepines appear to be confined to a few Vilsmeier reactions. 8-Chloro-l//-l-benzazepin-2-one with a mixture of DMF and POCl3 yields the 2,8-dichloro aldehyde (106) (72CPB1325). Under similar conditions Ar-mesyl-4,5-dihydro-3//-3-benzazepine formylates at the 1-position (107 R1 = CHO, R2 = H) (71BSF3985). In contrast, (V-mesyl-1,2,4,5-tetrahydro-3/7-3 -benzazepin-1 -one yields a mixture of the 1-chloro dihydro compound (107 R1 = Cl, R2 = H) and the chloro aldehyde (107 R1 = Cl, R2 = CHO). 

The alkaloids of the narcotine type can also be synthesized from benz[d]indeno(l,2-f ]azepine (133a) (698) (Scheme 45). Moreover, compound 133a forms a key substance for the synthesis of the tetrahydro-protoberberine (58), protopine (101), rhoeadane (154), and spiroben-zylisoquinoline (191) ring skeletons. The compounds 133a and 133b arise also by rearrangement from the spirobenzylisoquinoline, protoberberine, and 1-benzoylisoquinoline skeletons. Therefore, it is assumed that even in the plants it plays a key role in the formation and interconversion of the benzylisoquinoline alkaloids with 17 carbon atoms in the skeleton (Scheme 45). 

Condensation of 57 with homoveratraldehyde (60) in the presence of molecular sieves, followed by sodium borohydride reduction, affords the chromium tricarbonyl complex 61 in moderate overall yield. The acid-promoted cyclization of 61 proceeds with retention of configuration to afford, after air decomplexation, optically pure (/ )-( + )- -phenyl- 3-methyl-l,2,4,5-tetrahydrobenz[d]azepine (62) (Scheme 12) [14]. The l,2,4,5-tetrahydro-3//-benz-[benzazepine alkaloids . Moreover, the dopaminergic activity possessed by this class of compounds resides mostly in the (i )-enantiomer [15,16]. 

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