天冬氨酸单体及其聚合物的制备研究
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摘要
天冬氨酸是构成蛋白质的20种基本氨基酸之一，它在生化试剂和临床医学方面具有广泛的应用。聚天冬氨酸则是近年来人们发现的一种新型水处理剂和农作物营养吸收强化剂，由于它可以完全生物降解，属绿色化学品。有关天冬氨酸和聚天冬氨酸的研究在国外已经成为热点。美国、德国等国家已相继建成较大规模的生产装置并成功运转。而国内只有一些少量的报道。本文工作成功地开发出了顺丁烯二酸酐的氨化法合成天冬氨酸单体，并且对单体合成工艺中有较大污染的酸化结晶步骤进行了改进，提出了采用顺丁烯二酸进行酸化的循环回收工艺。以顺丁烯二酸酐和浓氨水为原料采用直接液相聚合的方法合成了聚天冬氨酸。研究了聚琥珀酰亚胺水解的动力学，并对聚天冬氨酸产品的阻垢性能作了测试。
研究了顺丁烯二酸酐的氨化法合成天冬氨酸单体的新工艺。与传统工艺相比，这一工艺具有原料易得，过程简单，反应条件温和，产物易分离等特点。最优工艺条件为：顺丁烯二酸酐41.8g，反应温度135℃；加入的水量为80ml；反应液的pH值调节为9.5；打压压力为1.2MPa；保温反应时间为4.5～5.0h；当采用盐酸酸化时，调节pH值至2.5结晶；当采用顺丁烯二酸酸化时，调节pH值至3.8结晶。在该最优工艺条件下，DL-天冬氨酸的收率可以达到70％以上，超过文献报道的最高63％，纯度达到95％以上。
研究了以顺丁烯二酸酐和浓氨水为原料合成了聚天冬氨酸的聚合反应工艺。通过控制工艺条件，直接液相聚合得到了聚琥珀酰亚胺。最优工艺条件为：加料中氨比为1.1，在165℃的温度下加热4分钟左右，再自然冷却(升温过程也是逐步的)得到较纯的聚琥珀酰亚胺(PSI)。将聚琥珀酰亚胺在碱性条件下水解后即可得较纯的PASP的钠盐产品。将该钠盐产品再酸化即可得到PASP。
聚天冬氨酸产品的的阻垢性能测试表明，在pH值为8.0的条件下，当水中CaCO_3浓度为：450mg／l时，聚天冬氨酸的投加量为：2.22mg／l即可达到94.7％的阻垢效率。
对聚琥珀酰亚胺水解动力学研究结果表明，水解过程符合缩核模型。活化能数据为：DL-聚琥珀酰亚胺与NaOH反应的活化能为75.1kJ／mol。
Aspartic acid is one of the twenty kinds of basic aminos which make up the protein, it has been used in biochemical reagents and clinical medicine . Poly(aspartic acid) has been found to be able inhibit scale in water and promote the ability for crops to absorb nutrition. Since it is completely biodegradable it belongs to green chemical. Research on aspartic acid and poly(aspartic acid) has become a central issue abroad while there is few reports about it in China until now. In this article, some novel technologies has been developed for the synthesis of aspartic acid and poly(aspartic acid). These technologies can be described as below: Aspartic acid is synthesized by the reaction of maleic anhydride and ammonia in water in a autoclave and the mother liquid is acidified by maleic acid for reduction the waste. Poly(succinimide) is synthesized by the directly reaction of maleic anhydride and ammonia in water. The hydrolysis kinetics of Poly(succinimide) was investigated. In addition, the performance of the product of poly(aspartic acid) to inhibit scale was investigated.
The present aspartic acid synthesis method has many advantages over the traditional technologies. The optimal reaction conditions are: 41.8 g maleic anhydrde, 135 ?, 80 ml H2O, pH=9.5, 1.2 MPa, reaction time 4.5 ~ 5.0 h. acidified by hydrochloric acid, pH=2.5, acidified by maleic acid, pH=3.5 ~ 4.0. Under these conditions, the yield of aspartic acid was above 70% which much higher than those reported in the literature and the purity more than 95%.
Poly(aspartic acid) can be obtained from maleic anhydride and ammonia. Poly(succinimide) is synthesized by the directly reaction of maleic anhydride and ammonia in water by controlling the process conditions. The optimal reaction conditions are: the ratio of ammonia and maleic anhydride is 1.1, 165?, reaction time 4 min. After hydrolysis of Poly(succinimide) with base, poly(aspartic acid) is obtained.
The performance of poly(aspartic acid) in scale inhibition shows that the scale inhibition efficiency of poly(aspartic acid) can reach to 94.7% when pH value was 8.0.
Kinetic studies of poly(succinimide) shows that the hydrolysis of poly(succinimide) obeys the shrinking core model. The active energy of the reaction between poly(succinimide) and NaOH was 75.1 kJ/mol.
研究了顺丁烯二酸酐的氨化法合成天冬氨酸单体的新工艺。与传统工艺相比，这一工艺具有原料易得，过程简单，反应条件温和，产物易分离等特点。最优工艺条件为：顺丁烯二酸酐41.8g，反应温度135℃；加入的水量为80ml；反应液的pH值调节为9.5；打压压力为1.2MPa；保温反应时间为4.5～5.0h；当采用盐酸酸化时，调节pH值至2.5结晶；当采用顺丁烯二酸酸化时，调节pH值至3.8结晶。在该最优工艺条件下，DL-天冬氨酸的收率可以达到70％以上，超过文献报道的最高63％，纯度达到95％以上。
研究了以顺丁烯二酸酐和浓氨水为原料合成了聚天冬氨酸的聚合反应工艺。通过控制工艺条件，直接液相聚合得到了聚琥珀酰亚胺。最优工艺条件为：加料中氨比为1.1，在165℃的温度下加热4分钟左右，再自然冷却(升温过程也是逐步的)得到较纯的聚琥珀酰亚胺(PSI)。将聚琥珀酰亚胺在碱性条件下水解后即可得较纯的PASP的钠盐产品。将该钠盐产品再酸化即可得到PASP。
聚天冬氨酸产品的的阻垢性能测试表明，在pH值为8.0的条件下，当水中CaCO_3浓度为：450mg／l时，聚天冬氨酸的投加量为：2.22mg／l即可达到94.7％的阻垢效率。
对聚琥珀酰亚胺水解动力学研究结果表明，水解过程符合缩核模型。活化能数据为：DL-聚琥珀酰亚胺与NaOH反应的活化能为75.1kJ／mol。
Aspartic acid is one of the twenty kinds of basic aminos which make up the protein, it has been used in biochemical reagents and clinical medicine . Poly(aspartic acid) has been found to be able inhibit scale in water and promote the ability for crops to absorb nutrition. Since it is completely biodegradable it belongs to green chemical. Research on aspartic acid and poly(aspartic acid) has become a central issue abroad while there is few reports about it in China until now. In this article, some novel technologies has been developed for the synthesis of aspartic acid and poly(aspartic acid). These technologies can be described as below: Aspartic acid is synthesized by the reaction of maleic anhydride and ammonia in water in a autoclave and the mother liquid is acidified by maleic acid for reduction the waste. Poly(succinimide) is synthesized by the directly reaction of maleic anhydride and ammonia in water. The hydrolysis kinetics of Poly(succinimide) was investigated. In addition, the performance of the product of poly(aspartic acid) to inhibit scale was investigated.
The present aspartic acid synthesis method has many advantages over the traditional technologies. The optimal reaction conditions are: 41.8 g maleic anhydrde, 135 ?, 80 ml H2O, pH=9.5, 1.2 MPa, reaction time 4.5 ~ 5.0 h. acidified by hydrochloric acid, pH=2.5, acidified by maleic acid, pH=3.5 ~ 4.0. Under these conditions, the yield of aspartic acid was above 70% which much higher than those reported in the literature and the purity more than 95%.
Poly(aspartic acid) can be obtained from maleic anhydride and ammonia. Poly(succinimide) is synthesized by the directly reaction of maleic anhydride and ammonia in water by controlling the process conditions. The optimal reaction conditions are: the ratio of ammonia and maleic anhydride is 1.1, 165?, reaction time 4 min. After hydrolysis of Poly(succinimide) with base, poly(aspartic acid) is obtained.
The performance of poly(aspartic acid) in scale inhibition shows that the scale inhibition efficiency of poly(aspartic acid) can reach to 94.7% when pH value was 8.0.
Kinetic studies of poly(succinimide) shows that the hydrolysis of poly(succinimide) obeys the shrinking core model. The active energy of the reaction between poly(succinimide) and NaOH was 75.1 kJ/mol.
引文
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[6] 吕正荣，于加会，卓仁僖等．聚(L-天冬氨酸)衍生物-顺铂结合物的制备及体外细胞毒性研究．高等学校化学学报．1998，19(5)：817～820．
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[12] Kinnersley AM, Koskan LP, Strom DJ, etc., Inventors Donlar Cor., Assignee. US 5,350,735. 1994-09-27.
[13] Boehmke G, Inventor. Bayer Aktiengesellschaft, Assignee. US 4,839,461.1989-06-13.
[14] Mannich bases of acylaminomalonates and a synthesis of DL-aspartic acid. R. O.Atkinson (Brit. Drug Houses Ltd., London). J. Chem. Soc. 1952, 3317-18..
[15] Synthesis of DL-aspartic acid-4-C~(14). M. I. Lerman and V. I. Mainind (Med. Inst.,Moscow). Voprosy Med. Khim. 6, No. 2, 203-5 (1960).
[16] Giovanni Ferrari and Rolando Cultrera (Univ. Padua, Italy). Gazz. Chim. Ital. 90,1637-44(1960); cf. G. Ferrari, ibid., No. 11,1522.
[17] Krishna Bahadur and Krishna Murari Lal Agrawal (Univ. Allahabad, India). J.Chem. U.A.R. 9(1), 67-72(1966).
[18] 生物有机化学／古练权 马林．-北京：高等教育出版社：德国：施普林格出版社．1998：41～50．
[19] 化工百科全书．化工百科全书编委会：第一卷，北京：化学工业出版社．1990．84．
[20] 邓润华，宓爱巧，蒋耀忠．微波快烷基化合成a-氨基酸．应用化学，1993，10(5)：108～109
[21] 谭佩章，陶宗晋，祁国荣．现代化学试剂，第三册(一)．北京：化学工业出版社．1986．15．
[22] Frankel, M., Liwscbitz, Y. and. Amiel, Y.: J. Am. Chem. Soc., 1953,75,330.
[23] The mechanism of synthesis of amino acids by electric discharges. Stanley L.Miller, Biochimi. Biophys. Acta 23.480 (1957)
[24] Amino acid synthesis form an amorphous substance composed of carbon, nitrogen,and oxygen. Shin Miyakawa, Hideki Tamura and Akira B. Sawaoka. Appl. Phys.Lett., Vol. 72, No. 8, 23 February 1998.
[25] Amino acid synthesis from CO_2-N_2 and CO_2-N_2-H_2 gas mixtures via complex organic compounds. S. Miyakawa, K. Kobayashi and A.B.Sawaoka. Adv. Space Res. Vol.24,No.4,pp.465～468,1999.
[26] Amination of ester enolates with O-(2,4-Dinitrophenyl)hydroxylamine. Arakali S.Radhakrishna and G. Marc Loudon. J. Org. Chem., Vol.44,No.26,1979 4836～4841
[27] 蒋耀忠，陈代谟，立广年．固-液相转移催化合成(Ⅰ．通过醛亚胺的烷基化合成a-氨基酸．)．化学学报，1985，43，275～277．
[28] Ruthenium tetroxide oxidation of amines. New general synthesis of amino acids. David C. Ayres. J. Chem. Soc., Chem. Commun. 1975, (11), 440-1 (Eng).
[29] Synthesis of amino acids. Naseem H. Khan, Amin A. Srddiqui and A.R.Krdwai.Indian J. Chem., Sect. B 1977, 15 B(6), 573-4.
[30] Machowski S, Twardowski J, Tichek P, Inventors. Spoldzielnia Pracy Chemikow 'Xenon',Assignee. 1986-08-30,PL 133 691.
[31] Korner M, Inventor. BASF A-G., Assignee. DE 4,427,631.1996-02-08.
[32] Kratz D, Witzel T, Boezner R, etc., Inventors. BASF A-G., Assignee. DE 4,034,172.1996-03-28.
[33] Larry P. Koskan, Orland Park, Abdul R.Y. Meah, Inventors. Donlar Cor. Assignee.US 5,219,952. 1993-07-15.
[34] Fujii CT, Nishibayashi H, Hideyuki, Inventors. Nippon Catalytic Chem. Ind.,Assignee. JP 08,143,679. 1996-06-04.
[35] Kroner M, Schornick G, Baur R, Potthoff B, Inventors. BASF A.-G., Assignee. DE 4,427,278. 1996-12-15.
[36] Harada K, Shimoyama A, Mizumoto H, Inventors. Fuyo Kagakn Kogyo K.,Assignee. JP 61,218,634. 1986-09-29.
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