N-(甲酰基吡嗪)-α-氨基酸甲酯的合成

Synthesis of N-(Formyl pyrazine)-α-amino Acid Methyl Esters

以2,3-吡嗪二羧酸和α-氨基酸(甘氨酸、缬氨酸、亮氨酸)为原料,在氯化亚砜的作用下,采取分步法和一步法,得到不同的吡嗪酰胺类衍生物,其结构经1HNMR、13CNMR、IR和HR-MS等方法确定。探讨了不同反应条件对吡嗪酰胺类衍生物合成的影响。结果表明,在氯化亚砜的作用下,采用分步法和一步法,分别得到N-(2-羧基-3-甲酰基吡嗪)-α-氨基酸甲酯和N-(2,3-二甲酰基吡嗪)-α-氨基酸甲酯。其最优反应条件为:在分步法和一步法中,α-氨基酸甲酯盐酸盐与Et3N的摩尔比约为1∶2.1时,氨基释放完全,目标产物的收率最高;分步法2,3-吡嗪二甲酰氯盐酸盐的制备采用直接抽滤为最优方法,收率达75%以上;一步法N-(2,3-二甲酰基吡嗪)-α-氨基酸甲酯的制备中,氯化亚砜的量为6 mL时,收率最高。从整体来看,分步法的收率较高,均50%以上。

Under the action of thionyl chloride, different pyrazinamide derivatives were obtained from 2, 3-pyrazinedicarboxylic acid and α-amino acids （ glycine, valine, leucine） by methods of fractional steps and one step. Its structure was confirmed by ^1 HNMR,^13 CNMR, IR and HR-MS spectral analysis. The effect of different reaction conditions on the synthesis of pyrazinamide derivatives was discussed. The results show that in the presence of thionyl chloride, N-（2-carboxy-3-formyl-pyrazine）-α-amino acid methyl ester and N-（ 2,3-acyl dimethyl pyrazine ）-α-amino acid methyl esters were obtained by methods of fractional steps and one step respectively. The optimal synthesis conditions were determined as follows：the amino group was released completely and the highest yield of the target product was obtained when the material ratio of α-amino acid methyl ester hydroehloride to Et3N was about 1：2. 1 in the one-step and stepwise methods; in the stepwise process, the yield of 2,3-pyrazinedicarboxylic chloride hydrochloride was more than 75%, and the best method was to use direct filtration ;in the one- step process, the yield of N-（ 2,3-pyrazine-dimethyl acyl）-α-amino acid methyl esters was highest when the amount of thionyl chloride was 6 mL. On the whole, the yields of stepwise process were all more than 50%.