The Synthesis And Asymmetric Phase-transfer Catalytic Alkylation Of Schiff Bases Of L-Dopa

The dopamine is an important medicine in medical science , L-dopa separated from natural Macuna bean in Guangxi is taken as a starting material to develop following research work :First, five kinds of dopamine Schiff base were synthesized by the reaction of L-Dopa and diverse aromatic aldehydes and ketones , the four among those Schiff bases are new compounds that were not reported by literature . The result showes that the L-dopamine Schiff base of benzophenone was transferred into the dextrortatory compound. However, benzaldehyde, p-chlorobenzaldehyde, p-nitrobenzaldehyde ,3- methoxy-4-hydroxybenzaldehyde are still kept levorotatory and optical purity is dicreased in order, the result may be associated with steric hinder and electronic factor .Second, the methylation of five kinds of Schiff bases was researched under the condition of tetrabutyl ammonium bromide as a phase transfer catalyst and the influences of different temperature, solvent, reaction time and different inorganic alkali on methylation were investigated. The result see below : 1) The reaction speed is increased according to the sequence of p-nitrobenzaldehyde, p-chloro- benzaldehyde, benzaldehyde, 3-methoxy-4-hydroxybenzaldehyde, benzophenone Schiff bases. The result was in accordance with the influence of electronic factor and steric hinder.2) The optical activity of methyldopa synthesized is decised mainly by the optical activity of L-dopamine Schiff base. When the L-dopamine Schiff bases were levorotatory, the methyldopa obtained by the reaction is levorotatory also ([α]25D = -22.6o,e.e.%=75.3; [α]25D = -20.2o,e.e.%=67.3; [α]25D = -17.6o,e.e.%=58.6; [α]25D = -10.6o, e.e.%=35.3), vice versa.The optical purity is decreased gradually in order according to benzaldehyde, p-chlorobenzaldehyde, 3-methoxy-4-hydroxybenzaldehyde Schiff bases. 3) The lower the reaction temperature is, the higher the chemical yield is, the higher the optical purity of methyldopa is .At the same time, the influence of different phase-transfer catalysts on methylation of benzaldehyde L-dopamine Schiff base was investigated.When tetrabutylammonium bromide was used as a phase-transfer catalyst, the optical purity of methyldopa was 75.3%. However , when N-benzylquinium chloride and N- benzylcinchonium chloride with optical activity were used as catalyst , the optical purity of methyldopa was 76.3% and 78.6%. All methylating products were levorotatory , the result showed that double asymmetric induction had not appeared during the reaction and the optical rotation of methyldopa is decided by the asymmetry of Schiff base, the optical activity of the catalyst has no influence to methylation .Moreover, the ethylation and benzylation of benzaldehyde and p-chlorobenzaldehyde L-dopamine Schiff bases were studied also.The result showed that the chemical yield of alkylation is much lower, which may be resulted by steric hinder. Product obtained by benzylation of L-dopamine Schiff base was changed into dextrorotaory, this result may be produced by change of configuration of the compound. Contrary, the ethylating product was kept a high levorotatory. When p-chlorobenzaldehyde Schiff base was used, the similar result is obtained with the ethylation and benzylation of benzaldehyde Schiff base, the different result in optical activity may be associated with steric hinder and electronic factor .