Reaction of the water-soluble reagent N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide with nucleophiles: participation of the tautomeric cyclic ammonioamidine as a kinetically important intermediate
Reaction of the water-soluble reagent N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide with nucleophiles: participation of the tautomeric cyclic ammonioamidine as a kinetically important intermediate
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水溶性试剂 N-乙基-N-(3-二甲基氨基丙基)碳二亚胺与亲核试剂的反应：互变异构环氨脒作为动力学上重要的中间体的参与
DOI：
10.1021/ja00491a053
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发表时间：
1978
影响因子：
15
通讯作者：
A. Williams
中科院分区：
文献类型：
--
作者：
I. T. Ibrahim;A. Williams
根据方案I，使用类似于等式1的等式; 5 b，使用K2、K2和K4的已知值，我们可以估计K2和K2分别为< 10 - 11和> 1。脒（K2）的电离pAla相对较低，可能是由于强吸电子的氨基团。假设平衡的物种II-VI和限速质子催化水解的游离碳化二亚胺VI，我们可以估计的酸平台速率常数（pH 0-4）从质子攻击的三甲铵模型（&h= 3 × 102 M-1 s-1）。试剂I的总速率常数在酸平台区变为Kt 1 K1 K2 K2/Kh 5 q，其给出3 × 10- 2s-1，代入平衡常数和k的值。估计值远大于观察到的值（10 - 3s-1），表明步骤之一是碳二亚胺机理的速率限制。VI的分解速率常数随着pH的降低而增加，并且K2可能成为限速步骤，因为这是pH独立的，并且其他步骤涉及质子转移到电负性原子和从电负性原子转移。生产V的总速率常数是氢氧离子依赖性的，因此，在酸性区域观察到的低的pH独立的速率常数与不同的机制一致，即水对铵脒二价阳离子（II）的攻击。I在碱性pH区的水解遵循中性模型A/N ′-二-w-丙基碳二亚胺的水解。假设物种II-VI处于平衡状态，并使用上面推导出的平衡常数值，我们估计在碱性区域中以V存在的试剂I的分数为50%;另外50%为IV。因此，我们应该预期在相应pH下观察到的速率常数比模型的速率常数小约50%。（图1）证实碱性水解通过中性碳二亚胺V进行。在pH 5.4下乙酸盐（1 M）缓冲液对三甲基铵基碳二亚胺的攻击具有1.6 × 10 - 3s-1的速率常数;在pH5.4时，用上述测定的平衡常数计算质子化碳二亚胺VI的比例为0.091。I与1的预测速率常数
Communications to the Editor 7421 rium from Scheme I with an equation similar to eq 1; 5b using the known values for K2K2 and K4 we may estimate K2 and K2 to be< 10 “11 and> 1, respectively. The ionization pAla for the amidine {K2) is relatively low presumably owing to the pow-erfully electron-withdrawingammonio group. Assuming equilibrium of the species II—VI and rate-limiting proton-catalyzed hydrolysis of the free carbodiimide VI, we may estimate the acid plateau rate constant (pH 0-4) from proton attack on the trimethylammonio model (&h= 3 X 102 M-1 s_1). The overall rate constant for reagent I becomes kt\K\K2K2/Kh5q in the acid plateau region which gives 3 X 10-2 s_l on substituting values for the equilibrium constants and &· The estimated value is much larger than that observed (10~ 3 s_1) indicating that one of the steps]-is rate limiting for the carbodiimide mechanism. The decomposition rate constant for VI increases with decrease in pH and it is likely that K2 becomes the rate-limiting step because this is pH independent and the other steps involve proton transfer to and from electronegative atoms. The overall rate constant for production of V is hydroxide ion dependent and the observation of the low, pH independentrate constant in the acid region is therefore consistent with a different mechanism, namely water attack on the ammonioamidinium dication (II). Hydrolysis of I in the alkaline pH region follows the hy-drolysis of the neutral model A/TV'-di-w-propylcarbodiimide. Assuming that species II—VI are in equilibrium and using values of the equilibrium constants deduced above, we estimate that the fraction of reagent I present as V is 50% in the alkaline region; the other 50% is IV. Thus we should expect an observed rate constant some 50% less than that of the model at the corresponding pH. The close proximity of the data (Figure 1) confirms that the alkaline hydrolysis proceeds via the neutral carbodiimide V.Attack of acetate (1 M) buffer on the trimethylammoniocarbodiimide at pH 5.4 has the rateconstant 1.6 X10-3 s_ 1; at pH 5.4 the proportion of protonated carbodiimide VI is calculated to be 0.091 usingthe equilibrium constants determined above. The predicted rateconstant for I with 1