Study On Synthesis And Technology Of 2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl) Benzylamine

2-Amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl) benzylamine as hydrochloride salt is a pharmaceutical intermediates used for expectorant drug, which prepared from the reductive amination of 2-amino-3,5-dibromobenzaldehyde with trans-4-aminocyclohexanol in methanol by using NaBH4 as reducing agent. The precursor 2-amino-3,5--dibromobenzaldehyde was produced by bromination of o-aminobenzaldehyde which originated from o-nitrobenzaldehyde.The reduction of the ingredient o-nitrobenzaldehyde using Fe powder was discussed in the presence of acids and electrolytes. The results showed that 95% yield of o-aminobenzaldehyde was gained under the refluxing temperature by using catalytic amounts of concentrated hydrochloric acid, an ethanol-water solvent system of 4:1 (v/v), and the reactants amounts ratio of 10:1.0 in Fe to o-nitrobenzaldehyde.Meanwhile the bromination of o-aminobenzaldehyde could be conducted in molecular bromine, and aq. KBr and 30%H2O2 could obviously improve the utilization of bromine. The yield of 2-amino-3,5-dibromobenzaldehyde was 93.3% when the ratio of KBr, bromine and o-aminobenzaldehyde was 9.50:1.93:1.00 by adding dropwise aq. KBr and bromine at 20℃. Otherwise the yield of 2-amino-3,5-dibromobenzaldehyde was 73.1% when the ratio of bromine and o-aminobenzaldehyde was 1.06:1.00 by the dropwise of 30%H2O2 and bromine at 20℃.The 72.3% yield of 2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl) benzylamine was achieved by the amination of 2-amino-3,5-dibromobenzaldehyde with 4-trans--aminocyclohexanol under refluxing temperature with the molar ratio of 1.0:1.9 with NaBH4 reductive agents.