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1) The reaction of 10-methoxy-5H-dibenz[b,f]azepine (I) with phosgene in hot toluene gives 10-methoxy-5H-dibenz[b,f]azepine-5-carbonyl chloride (II), which is treated with NH3 in refluxing ethanol to afford 10-methoxy-5H-dibenz[b,f]azepine-5-carboxamide (III). Finally, this compound is hydrolyzed with refluxing 2N HCl.

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2) The nitration of 5-cyano 5H-dibenz[f,b]azepine (IV) with NaNO2 in acetic anhydride - acetic acid gives 5-cyano 10-nitro-5H-dibenz[b, f]azepine (V), which is then treated with BrF3 and powdered Fe in hot acetic acid.

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Syntheses of intermediate (V), 5-benzyl-10,11-dihydro-5H-dibenz[b,f]azepin-10-one: Cyclization of either 2-[N-benzyl-N-(2-methylphenyl)amino]-N,N-dimethylbenzamide (I), 2-[N-benzyl-N-(2-methylphenyl)amino]-N,N-diethylbenzamide (II), 2-[N-benzyl-N-(2-methylphenyl)amino]-N,N-diisopropylbenzamide (III) or the morpholine derivative (IV) by means of LDA and TMEDA in THF.

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Syntheses of intermediate (VIII), 5-(4-methoxybenzyl)-10,11-dihydro-5H-dibenz[b,f]azepin-10-one: Cyclization of 2-[N-(4-methoxybenzyl)-N-(2-methylphenyl)amino]-N,N-dimethylbenzamide (VI) or 2-[N-(4-methoxybenzyl)-N-(2-methylphenyl)amino]-N,N-diethylbenzamide (VII)) by means of LDA and TMEDA in THF.

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Syntheses of intermediate (XI), 5-allyl-10,11-dihydro-5H-dibenz[b,f]azepin-10-one: Cyclization of 2-[N-allyl-N-(2-methylphenyl)amino]-N,N-dimethylbenzamide (IX) or 2-[N-allyl-N-(2-methylphenyl)amino]-N,N-diethylbenzamide (X) by means of LDA and TMEDA in THF.

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Finally, deprotection of either intermediate (V) with TMS-Cl and NaI, intermediate (VIII) with TiCl4 or intermediate (XI) with Rh(PPh3)3Cl give, in all cases, 10,11-dihydro-5H-dibenz[b,f]azepin-10-one (XII), which is finally treated with chlorosulfonyl isocyanate to afford oxcarbazepine.

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This compound has been obtained by two related ways: 1. The hydrolysis of 10-methoxy-5H-dibenzo[b,f]azepine (I) with refluxing 2N HCl gives 10,11-dihydro-5H-dibenzo[b,f]azepin-5-one (II), which is then treated with chlorosulfonyl isocyanate in chloroform to yield the target carboxamide. 2. The reaction of 10-methoxy-5H-dibenzo[b,f]azepine (I) with potassium cyanate in hot sulfuric acid also gives the target carboxamide. In this reaction sodium cyanate can also be used instead of the potassium salt. Other strong acids such as trichloroacetic acid or anhydrous HCl in acetic acid can be used instead of sulfuric acid.

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A new process for the preparation of oxcarbamazepine has been reported: Reaction of 1-phenyl-2,3-dihydro-1H-indol-2-one (I) with NaOH in refluxing THF gives 2-[2-(phenylamino)phenyl]acetic acid (II), which is condensed with dimethyl carbonate (III) by means of butyl lithium in the same solvent to yield 2-[2-[N-(methoxycarbonyl)-N-phenylamino]phenyl]acetic acid (IV). Cyclization of compound (IV) by means of polyphosphoric acid (PPA) at 100 C, followed by treatment of the reaction mixture with hot methanol (65 C) affords 10-methoxy-5H-dibenzo[b,f]azepine-5-carboxylic acid methyl ester (V), which is treated with NaOH in polyethyleneglycol at 100 C to provide 10-methoxy-5H-dibenzo[b,f]azepine (VI). Reaction of (VI) with sodium cyanate in acetic acid gives 10-methoxy-5H-dibenzo[b,f]azepine-5-carboxamide (VII), which is finally treated with H2SO4.

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