Lee H K, Querijero G
J Pharm Sci. 1985 Mar;74(3):273-6. doi: 10.1002/jps.2600740310.
Thioamide, 1, is shown to exist as two rotameric forms in solution, rotamer A and B. Conformations of the rotamers are defined to be trans for rotamer A and cis for rotamer B. Energy barriers restricting rotation about the C--N bond of the thioamide group are examined as a function of pH, temperature, buffer concentration, ionic strength, and dielectric constant. Kinetic parameters, kobs, k1, k2, Ea, delta S not equal to, delta H not equal to, and Keq are obtained. No significant buffer effect is observed. Ionic strength (0.2-0.8) does not markedly affect the rate of interconversion. The extent of reaction (Keq) is related to dissociation of the carboxylic acid function. The reaction rate decreases with increasing polarity of solvent which retards interconversion. The energy barriers (Ea = 25-26 kcal/mol) are almost invariant with changing pH values. When protected from light, rotamer A is thermodynamically more stable than rotamer B. The rotamer ratio is dependent on pH and temperature. Under 500 foot-candle light exposure, the ratio of rotamer A to B is close to one at 30 degrees C.
硫代酰胺（1）在溶液中以两种旋转异构体形式存在，即旋转异构体A和B。旋转异构体的构象定义为：旋转异构体A为反式，旋转异构体B为顺式。研究了限制硫代酰胺基团C-N键旋转的能垒与pH、温度、缓冲液浓度、离子强度和介电常数的关系。获得了动力学参数kobs、k1、k2、Ea、ΔS≠、ΔH≠和Keq。未观察到明显的缓冲效应。离子强度（0.2 - 0.8）对互变速率没有显著影响。反应程度（Keq）与羧酸官能团的离解有关。反应速率随着溶剂极性的增加而降低，这阻碍了互变。能垒（Ea = 25 - 26 kcal/mol）几乎不受pH值变化的影响。在避光条件下，旋转异构体A在热力学上比旋转异构体B更稳定。旋转异构体比例取决于pH和温度。在500英尺烛光的光照下，30℃时旋转异构体A与B的比例接近1。
