Marlier John F, Frey Thomas G, Mallory Jennifer A, Cleland W W
Department of Chemistry and Biochemistry, California Polytechnic State University, San Luis Obispo, California 93407, USA.
J Org Chem. 2005 Mar 4;70(5):1737-44. doi: 10.1021/jo0402733.
Multiple isotope effects have been measured for the acid-catalyzed hydrolysis of methyl formate in 0.5 M HCl at 20 degrees C. The isotope effects in the present investigation include the carbonyl carbon (13k = 1.028 +/- 0.001), the carbonyl oxygen (18k = 0.9945 +/- 0.0009), the nucleophile oxygen (18k = 0.995 +/- 0.001), and the formyl hydrogen ((D)k = 0.81 +/- 0.02). Determination of the carbonyl carbon, carbonyl oxygen, and formyl hydrogen isotope effects was performed via isotopic analysis of residual substrate. However, determination of the oxygen nucleophile isotope effect required analysis of the oxygen atoms of the product (formic acid), which exchange with the solvent (water) under acid conditions. This necessitated measurement of the rate of exchange of these oxygen atoms under the conditions for hydrolysis (k(ex) = 0.0723 min(-1)) and correction of the raw isotope ratios measured during the nucleophile-O isotope effect experiment. These results, along with the previously reported isotope effect for the leaving oxygen (18k = 1.0009) and the ratio of the rate of hydrolysis to that of exchange of the carbonyl oxygen with water (k(h)/k(ex) = 11.3), give a detailed picture of the transition-state structure for the reaction.
在20℃下于0.5 M盐酸中对甲酸甲酯的酸催化水解进行了多种同位素效应的测量。本研究中的同位素效应包括羰基碳（(^{13}k = 1.028 ± 0.001)）、羰基氧（(^{18}k = 0.9945 ± 0.0009)）、亲核氧（(^{18}k = 0.995 ± 0.001)）以及甲酰氢（((D)k = 0.81 ± 0.02)）。羰基碳、羰基氧和甲酰氢同位素效应的测定是通过对残留底物的同位素分析进行的。然而，亲核氧同位素效应的测定需要对产物（甲酸）的氧原子进行分析，这些氧原子在酸性条件下会与溶剂（水）发生交换。这就需要测量在水解条件下这些氧原子的交换速率（(k_{ex} = 0.0723 min^{-1})）并对亲核氧同位素效应实验中测得的原始同位素比率进行校正。这些结果，连同先前报道的离去氧的同位素效应（(^{18}k = 1.0009)）以及水解速率与羰基氧和水交换速率的比率（(k_h/k_{ex} = 11.3)），给出了该反应过渡态结构的详细情况。
