N-acetyl -3,4 - Dimethoxy-phenylalanine On The Synthesis Of,

In this paper, the subject we mainly discuss is the syntheses of N-acetyl-3, 4-dimethoxyphenylalanine (namely. N-acetyl- DL-veratrylglycine), which can be further used to manufacture L-DOPA (it is well known for its usefulness in treating the symptoms of Parkinson's disease). The synthesis route is as follows:Veratrylidene-hydantoin is obtained by condensation of veratryldehyde with hydantoin in the presence of ammonia: veratrylidene-hydantoin is hydrogenated to produce veratryl-hydantoin;veratryl-hydantoin is hydrolyzed with sodium hydroxide to obtain 3, 4-dimethoxyphenylalanine;then 3, 4-dimethoxyphenylalanine is acetylated and acidified with acetic anhydride and hydrogen chloride respectively to get the target compound. N-acetyl- 3. 4-dimethoxyphenylalanine.Experiment of this paper consists of four parts, the general procedure are as follows:The synthesis of veratrylidene-hydantoinAmmonia is used as the new inexpensive catalyst, the Aldol-Condensation reaction is performed between veratryldehyde and hydantoin, and then one molecule of water is removed, to produce veratrylidene-hydantoin. yellow solid substance.Veratryldehyde and hydantoin are mixed with water at 50℃. the mixture is agitated and the ammonia is added. Heating of the resulting mixture is continued at a reaction temperatures between 90 and 100℃. and at atmospheric pressures. The reaction is usually completed in a period of 8-10 hours.Veratryldehyde and hydantoin can be employed in various ratio, but for reason of economy are usually equimolecular or substantially equimolecular proportions, e.g. from 1.0 to 1.2 moles of hydantoin per mole of veratryldehyde. In this paper we adopt the proportion of 1.2 moles of hydantoin per mole of the veratryldehyde.The synthesis of veratryl-hydantoinVeratrylidene-hydantoin is reduced to the veratryl-hydantoin using the inexpensive Raney Nickel as the catalyst in the presence of the alkali.The reaction is carried out with sufficient amount of Ranev Nickel ranaina fromabout 10 to about 40 percent by weight of veratrylidene-hydantoin. In this paper, we adopt 25-30% by weight of veratrylidene-hydantoin.Veratrylidene-hydantoin is mixed with water, and then Raney Nickel catalyst is added;finally sufficient amount of liquid alkali is added to the reaction mixture.Hydrogen is bubbled in with vigorous stirring;the reaction is performed at elevated pressures, i.e. between 0.4 and 0.6MPa, the reaction temperature is maintained between 40 and 50°C (hot water bath). Reaction is generally completed in about 4 hours.? The synthesis of 3, 4-dimethoxyphenylalanineVeratryl-hydantoin is hydrolyzed at definite temperature and definite pressure in the presence of alkali to give 3,4-dimethoxyphenylalanine, red brown liquid substance.Alkali is added to the reaction mixture of veratryl-hydantoin and water, then the mixture is heated between 115 and 125 °C, at same time, the reaction pressure is maintained between 0.15 and-0.25 MPa, the reaction is completed in 4 hours.Alkali must be used in an amount sufficient to provide about 1 molar equivalent for the reaction and 1-2 molar equivalent to neutralize the products of reaction, e.g., amino acid and carbon dioxide. Preferably, to obtain maximum hydrolysis in a minimum period of time, considering the whole syntheses route, it is preferred that the molar equivalency of the alkali range from about 2 to about 6. In this paper, we adopt 4, i.e. the molar ratio of the veratryl-hydantoin to the alkali is 1 to 4.? The synthesis of N-acetyl-3, 4-dimethoxyphenylalanine3, 4-diethoxyphenylalanine is acetylated with acetic anhydride, and then further acidified with HC1, to give the target compound, N-acetyl-3, 4-dimethoxyphenylalanine, gray solid substance.The reaction mixture of 3, 4-dimethoxyphenylalanine and water is cooled in the range 20 to 25 °C, acetic anhydride is added at a rate such that the temperature of the reaction mixture is maintained below 25°C, until a pH of 8.0-9.0 is reached to obtain the N-acetyl-3, 4-dimethoxyphenylalanine (sodium salt).After the acetylation reaction, the reaction mixture is cooled to 20 °C, then is acidified with hydrogen chloride to a pH in the range of about 0.5 to 1.0. Adjust the adding speed to maintain the temperature in the range 20 °C to 25 °C. The targetcompound, N-acetyl-3, 4-dimethoxyphenyialanine, is obtainedThe amount used of the acetic anhydride and hydrogen chloride is based on required pH value and reaction terminals. ? Brief summaryThrough above description, the synthesis route in this paper is simpler and lower-cost, which can be easily performed in industry scale.