定义Definition
亲核取代反应是富电子的亲核试剂进攻缺电子碳（或其他原子），取代其上的离去基团的反应，主要有 SN1 和 SN2 两种极限机理。
Nucleophilic substitution is the attack of an electron-rich nucleophile on an electron-poor carbon (or other atom), displacing a leaving group; its two limiting mechanisms are SN1 and SN2.
SN1 与 SN2 对比SN1 versus SN2
SN2：一步协同，背面进攻，构型翻转，速率 = k[底物][Nu]，甲基 > 伯 > 仲（叔不行），偏好强亲核试剂和极性非质子溶剂（DMSO、丙酮）。SN1：两步，经碳正离子，产物部分消旋，速率 = k[底物]，叔 > 仲（伯、甲基极难），偏好极性质子溶剂（水、醇）和弱亲核试剂，可能重排。
SN2: one concerted step, backside attack, inversion, rate = k[substrate][Nu], methyl > 1° > 2° (not 3°), strong nucleophiles and polar aprotic solvents (DMSO, acetone). SN1: two steps via a carbocation, partial racemisation, rate = k[substrate], 3° > 2° (1° and methyl rarely), polar protic solvents and weak nucleophiles, possible rearrangement.
离去基团与亲核性Leaving groups and nucleophilicity
好的离去基团是弱碱：I⁻ > Br⁻ > Cl⁻ ≫ F⁻；TsO⁻、TfO⁻ 极好；–OH 需质子化或转化为磺酸酯。质子溶剂中亲核性 I⁻ > Br⁻ > Cl⁻ > F⁻（溶剂化），非质子溶剂中顺序可反转。
Good leaving groups are weak bases: I⁻ > Br⁻ > Cl⁻ ≫ F⁻, with TsO⁻ and TfO⁻ excellent; –OH must be protonated or sulfonated. Nucleophilicity in protic solvents is I⁻ > Br⁻ > Cl⁻ > F⁻ (solvation) and can reverse in aprotic solvents.
由来Origin
休斯与英戈尔德（1930 年代，伦敦大学学院）系统研究溶剂解动力学与立体化学，提出 SN1/SN2 分类与符号。
Hughes and Ingold (1930s, University College London) studied solvolysis kinetics and stereochemistry and introduced the SN1/SN2 classification.
反应Reactions
视机理与底物而定
Depends on mechanism and substrate
SN2：亲核试剂背面进攻，离去基团同时离去。
SN2: backside attack with simultaneous departure.
SN1：离去基团先离去形成碳正离子，亲核试剂再从两面进攻。
SN1: ionisation to a carbocation, then attack from either face.
伯卤代烃水解。
Hydrolysis of a primary halide.
叔丁基溴溶剂解。
Solvolysis of tert-butyl bromide.
反应机理图Mechanism
红色弯箭头表示一对电子的移动方向：从电子来源（孤对电子或化学键）指向电子去向。Red curly arrows show where an electron pair moves: from its source (lone pair or bond) to its destination.
亲核试剂从离去基团背面进攻，C–O 键形成与 C–Br 键断裂同步
Backside attack: the C–O bond forms as the C–Br bond breaks, in one step
构型翻转（瓦尔登翻转）
Inversion of configuration (Walden inversion)
年表Timeline
- 1896
瓦尔登翻转
Walden inversion
- 1935
休斯与英戈尔德提出 SN1/SN2
Hughes and Ingold propose SN1/SN2