Tsuji Yutaka, Toteva Maria M, Garth Heather A, Richard John P
Department of Biochemistry and Applied Chemistry, Kurume National College of Technology, Komorinomachi, Kurume 830-8555, Japan.
J Am Chem Soc. 2003 Dec 17;125(50):15455-65. doi: 10.1021/ja037328n.
Rate constant ratios for addition of the three nucleophilic sites of phenol to the 1-(4-methoxyphenyl)ethyl carbocation (1+) in 50/50 (v/v) trifluoroethanol/water were determined from the relative yields of the three phenol adducts, and absolute rate constants were determined from product rate constant ratios for addition of phenol and azide ion to 1+ using k(az) = 5 x 10(9) M(-1) s(-1) for the diffusion-limited reaction of azide ion. A selectivity of 230:20:1 was determined for alkylation of phenol at oxygen, C-4 and C-2 to form 1-OPh and biphenyls 1-(4-C6H4OH) and 1-(2-C6H4OH), respectively, and of 2:2:1 for alkylation of the corresponding nucleophilic sites of phenoxide ion in diffusion-limited reactions. The Mayr nucleophilicity parameter for C-4 of phenol is N = 2.0. Encounter-limited addition of phenoxide ion to 1+ to form 1-OPh is faster than encounter-limited addition of oxygen anions that are either more or less basic than phenoxide ion. Only the products of solvolysis are observed from acid-catalyzed cleavage of 1-OPh in 50/50 (v/v) trifluoroethanol/water, but a 50% yield of biphenyls 1-(4-C6H4OH) and 1-(2-C6H4OH) are observed from spontaneous cleavage of 1-OPh, where the leaving group is phenoxide ion, because of the very low kinetic barriers to collapse of the ion pair intermediate 1+.PhO-. The 230-fold larger rate constant for O-compared to C-2-alkylation of phenol is due primarily to the larger thermodynamic driving force for oxygen addition. There are similar Marcus intrinsic barriers for these two reactions.
根据三种苯酚加合物的相对产率，测定了在50/50（v/v）三氟乙醇/水中苯酚的三个亲核位点与1-（4-甲氧基苯基）乙基碳正离子（1+）加成的速率常数比，并使用叠氮离子扩散限制反应的k(az)=5×10⁹ M⁻¹ s⁻¹，根据苯酚和叠氮离子与1+加成的产物速率常数比确定了绝对速率常数。对于苯酚在氧、C-4和C-2处烷基化分别形成1-OPh和联苯1-（4-C₆H₄OH）和1-（2-C₆H₄OH），测定的选择性为230:20:1，对于扩散限制反应中酚盐离子相应亲核位点的烷基化，选择性为2:2:1。苯酚C-4的迈尔亲核性参数为N = 2.0。酚盐离子与1+的遭遇限制加成形成1-OPh比碱性比酚盐离子更强或更弱的氧阴离子的遭遇限制加成更快。在50/50（v/v）三氟乙醇/水中，酸催化1-OPh裂解仅观察到溶剂解产物，但从1-OPh自发裂解中观察到50%产率的联苯1-（4-C₆H₄OH）和1-（2-C₆H₄OH），其中离去基团是酚盐离子，因为离子对中间体1⁺.PhO⁻崩溃的动力学障碍非常低。与苯酚的C-2烷基化相比，O-烷基化的速率常数大230倍主要是由于氧加成的热力学驱动力更大。这两个反应有相似的马库斯内在势垒。
