本篇論文藉由羰基化合物（carboxylic compounds）水解反應的理論研究（結構、能量、天然鍵性軌域），來探討羰基化合物的水解能力。我們以X-CO-Y來代表羰基化合物本身，其中：X = H、CH3、n-C3H7、C6H5等4種取代基，Y = F、Cl、Br、NH2、NHCH3、N(CH3)2、OCH3、OC2H5、OC3H7、SH、SCH3、C6H5等12種離去基。
根據水解反應能，當X = CH3、n-C3H7、C6H5時我們可以將其水解能力大致區分成三個部分：C6H5、Cl、SH、Br、SCH3＞＞NH2、N(CH3)2、F、NHCH3＞OC3H7、OC2H5、OCH3；而當X = H時，後兩個部分的排列順序則變成OC2H5、OC3H7、F、NH2＞NHCH3、OCH3、N(CH3)2。根據計算結果，發現水解能力比較強的羰基化合物會有以下幾個特點：C－Y鍵能比較低，C－Y鍵長比較長，C＝O電荷差比較小，斷鍵反應的△E(2)值比較低，水解反應的△E(2)值比較高，lp2(O) →*C-Y的E(2)值比較大；而水解能力比較弱的則正好相反。由於Cl、SH、Br、SCH3擁有比較大的原子，以及C6H5擁有的*軌域，因此使得lp2(O) →*C-Y的E(2)值比較大，所以弱化C－Y鍵而導致水解反應容易進行。F原子因陰電性大使鍵能較大，根據計算結果其E(2)值比較大弱化C－Y鍵亦導致水解反應容易進行。其他的離去基可能的原因為所擁有的原子比較小，再加上本身並不含有利lp2(O) →*C-Y進行的因素，所以水解反應不容易進行。

Effects of the leaving group (Y = F, Cl, Br, NH2, NHCH3, N(CH3)2, OCH3, OC2H5, OC3H7, SH, SCH3, C6H5) on the hydrolysis of carboxylic compounds, X-CO-Y, have been studies by molecular orbital calculations. When X = CH3, n-C3H7 and C6H5, capabilities of X-CO-Y in undergoing hydrolysis are in the trend C6H5, Cl, SH, Br, SCH3 >> NH2, N(CH3)2, F, NHCH3 > OC3H7, OC2H5, OCH3. In the H-CO-Y series, a slight change for F and OR groups: C6H5, Cl, SH, Br, SCH3 >> OC2H5, OC3H7, F, NH2 > NHCH3, OCH3, N(CH3)2. The trend is generally understood based on the conjugation along Y-C=O fragments: a better mesomeric effect: Leaving groups that better in conjugation with carbonyl group will reduce the extents of hydrolysis of carboxylic compound.
For Y = F, the high tendency for hydrolysis can be explained by delocalization of the oxygen’s lone-pair electron(s) to the C-Y sigma antibonding. This is found by second-order perturbation energy analysis within the Natural Bond Orbital approach, which indicates the larger hyperconjugative interactions, lp2(O) → *C-Y, weakens the C-F bond more pronouncedly. This is ascribed to the low-lying energy of the *C-Y.

1. 陳岳鴻碩士編著，許延年博士校訂，有機化學，東華書局，臺灣台北，311頁，1988年9月初版。

2. 林經綸、陳昭雄主編，普通化學，文京圖書有限公司，臺灣台北，157頁，2001年5月10日第二版。

3. 李敏達著，物理化學，三民書局，臺灣台北，220頁，1985年再版。

4. F. A. Cotton, and G. Wilkinson著，彭育才譯，高等無機化學，國立編譯館出版，維新書局印行，臺灣台北，61頁，1965年。

5. D. G. Drueckhammer, and W. Yang; J. Am. Chem. Soc. 2001, 123, 11004.

6. A. Koch, B. Kallies, E. Kleinpeter, and R. Mitzner; J. Mol. Struct. 1997, 435, 123.

7. A. E. Reed, F. Weinhold, and L. A. Curtiss; Chem. Rev. 1988, 88, 899.

8. D. W. Landry, E. C. Sherer, G. Yang, G. C. Shields, and G. M. Turner; J.Phys.Chem.A.1997, 101, 8526.

9. F. Haurowitz著，程崇道譯，生物化學，教育部出版，臺灣台北，37頁，1959年。

10. C. G. Zhan , D. W. Landry, and R. L. Ornstein.; J. Am. Chem. Soc. 2000, 122, 2621.
11. B. L. Silver, and D. Samuel; Adv.Phys.Org.Chem.1965, 3, 123.

12. E. K. Fukuda, and R. T. Jr. Mclver; J. Am. Chem. Soc.1979, 101, 2498.

13. C. L. Johlman, and C. L. Wilkins; J. Am. Chem. Soc.1985, 107, 327.

14. J. P. Guthrie; J. Am. Chem. Soc.1991, 113, 3941.

15. A. Hengge; J. Am. Chem. Soc.1992, 114, 6575.

16. J. F. Marlier; J. Am. Chem. Soc.1993, 115, 5953.

17. C. G. Zhan, D. W. Landry, and R. L. Ornstein; J. Am. Chem. Soc.2000, 122, 1522.

18. D. Spangler, D. A. Femec, G. M. Maggiora, I. H. Williams, and R. L. Schowen; J. Am. Chem. Soc.1980, 102, 6621.

19. D. Spangler, D. A. Femec, G. M. Maggiora, I. H. Williams, and R. L. Schowen; J. Am. Chem. Soc.1983, 105, 31.

20. L. Berder; J. Am. Chem. Soc. 1951, 73, 1626.

21. A. Effio, and M. Cocivera; J. Am. Chem. Soc. 1976, 98, 1573.

22. I. Asubiojo, and I. Brauman; J. Am. Chem. Soc. 1979, 101, 3715.

23. E. H Chen, and T. C. Chang; J. Mol. Struct. (Theochem) 1998, 429, 153.

24. I. N. Levine; Quantum Chemistry, fifth edition, Prentice-Hall,Inc 2000.

25. A. D. Becke; Phys. Rev. A 1998, 38, 3098.

26. C. Lee, R. G. Parr, and W. Yang; Phys. Rev. B 1988, 37, 785.

27. CRC Handbook of chem & physics 85th Ed 2004~2005, 9-75.