General Papers
ARKIVOC 2015 (v) 230-241
approaches. Both of theses processes, described in detail in Scheme 1, are industrial procedures for the development of oxcarbazepine 5 at Novartis. COOH Cl
NH2
+ 7
HOOC
i
N H
8
N H
N H
10
11 iv
OCH3
vii
N H
15
iii
9
OCH3
O
14
O
13
(Me)2NOC
v
N
OCH3
O
OCH3
O
vi
N
viii
(Me)2NOC
ClOC
ii
OCH3
N O
OCH3
12
ix N
N O
NH2
O
16
NH2
5
Scheme 1. Reagents and conditions: (i) CuO/K2CO3, 170 C, 10h, (ii) SOCl2, 80 C, 2h, (iii) aq. Me2NH, 1h, reflux, (iv) n-BuLi, ClCOOCH3, (v) LDA, THF, 4h, (vi) HC(OCH3)3/ TsOH, MeOH, 5h, reflux, (vii) KOH, H2O/PEG, 8h, reflux, (viii) a. NaOCN; b. AcOH/H2O, 3h, (ix) HCl, 7h, reflux. Further synthetic approaches to compound 5 involved intramolecular Friedel-Crafts acylation of 2-carboxymethyldiarylamine intermediate to give 10-methoxyiminostilbene which upon carbamoylation and hydrolysis furnished 5.17 Recently, a palladium-catalyzed sequential Narylations reactions of substituted 2-(2-bromophenyl)-1-(2-(tosylamino)phenyl)ethanone was recently reported.18 This strategy was applied to the synthesis of not only of oxcarbazepine 5 but also of several structural analogs which incorporate arene or heteroarene rings. In recent communications we have demonstrated a very simple procedure for the synthesis of series of tricyclic keto derivatives of 10,11-dihydro-5H-dibenz[b,f]azepines 19,20 5,6-dihydro-11H-benz[f]pyrido[2,3-b]azepines20, 5,6,11,12-tetrahydro-5H(iminodibenzyls), dibenz[b,f]azocines and 5,6,11,12-tetrahydro-6H-benz[g]pyrido[2,3-c]azocines, via cyclialkylations of suitably synthesized nitrogen-containing alkanols and carboxylic acids. The results sustain the broad significance and utility of Friedel-Crafts cyclialkylations chemistry21 applied to the routine synthesis of difficult heterocyclic skeletons with the advantages of shorter reaction times and higher yields. In view of the above reports and in continuation of our interest in Friedel-Crafts ring closures22 as expedient alternative synthetic routes of novel and known heterocyclic systems, herein, we report the synthesis of 10,11-dihydro-10-oxo-5Hdibenz[b,f]azepine 3 by three different facile synthetic routes starting with easily prepared precursors.
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