定义Definition
SN2 是亲核试剂从离去基团背面进攻饱和碳原子、旧键断裂与新键形成同步完成的一步取代反应。反应速率同时取决于底物和亲核试剂的浓度,手性碳的构型发生翻转。
SN2 is a one-step substitution in which a nucleophile attacks a saturated carbon from the side opposite the leaving group, so that bond breaking and bond making happen together. The rate depends on both substrate and nucleophile concentrations, and a stereocentre is inverted.
机理与原理Mechanism and principle
亲核试剂的孤对电子进入 C–X 键的 σ* 反键轨道,因此只能从背面接近。过渡态中碳为五配位、三角双锥构型,三个取代基处于同一平面;离去后取代基像被风吹翻的雨伞一样翻转。速率方程 v = k[RX][Nu⁻],为二级反应。
The nucleophile's lone pair feeds into the σ* orbital of the C–X bond, so it can only approach from the back. The transition state has a five-coordinate, trigonal-bipyramidal carbon with three substituents in one plane; as the leaving group departs they flip over like an umbrella in the wind. The rate law v = k[RX][Nu⁻] is second order.
发现与由来Discovery and origin
1896 年瓦尔登发现,通过一系列取代反应可把 (−)-苹果酸转变为其对映体,即“瓦尔登翻转”。1935 年休斯与英戈尔德通过动力学与立体化学研究,提出 SN1 / SN2 命名,并把翻转归因于背面进攻。
In 1896 Walden found that a sequence of substitutions could turn (−)-malic acid into its enantiomer, the Walden inversion. In 1935 Hughes and Ingold, from kinetic and stereochemical studies, introduced the SN1 / SN2 labels and attributed inversion to backside attack.
影响因素Controlling factors
位阻顺序为甲基 > 伯 > 仲 ≫ 叔,叔卤代烃基本不发生 SN2。好的离去基团(I⁻ > Br⁻ > Cl⁻ ≫ F⁻)和强亲核试剂有利于反应。极性非质子溶剂(DMSO、DMF、丙酮)不溶剂化阴离子,可使速率提高几个数量级。
The steric order is methyl > primary > secondary ≫ tertiary; tertiary halides essentially do not react by SN2. Good leaving groups (I⁻ > Br⁻ > Cl⁻ ≫ F⁻) and strong nucleophiles favour it. Polar aprotic solvents (DMSO, DMF, acetone) leave anions unsolvated and can raise the rate by orders of magnitude.
与 SN1 和 E2 的竞争Competition with SN1 and E2
仲碳底物常在 SN2、SN1、E2 之间竞争:强碱、高温和位阻大的碱倾向 E2;质子性溶剂和能生成稳定碳正离子的底物倾向 SN1。合成中常用伯卤代烃配合弱碱性强亲核试剂(如 N₃⁻、CN⁻、I⁻)获得高选择性的 SN2。
Secondary substrates often compete among SN2, SN1 and E2: strong, bulky bases and heat favour E2, while protic solvents and substrates that form stable carbocations favour SN1. Synthetic chemists get clean SN2 by pairing primary halides with nucleophiles that are strong but weakly basic, such as N₃⁻, CN⁻ or I⁻.
反应Reactions
底物位阻小、离去基团好、亲核试剂强、极性非质子溶剂。
Unhindered substrate, a good leaving group, a strong nucleophile and a polar aprotic solvent.
亲核试剂从离去基团的背面(180°)接近碳原子。
The nucleophile approaches carbon from the back, 180° from the leaving group.
形成五配位三角双锥过渡态,Nu–C 键部分形成、C–X 键部分断裂。
A five-coordinate trigonal-bipyramidal transition state forms, with Nu–C partly made and C–X partly broken.
离去基团带着电子对离开,碳的构型翻转。
The leaving group departs with its electron pair and the carbon's configuration is inverted.
溴甲烷水解
Hydrolysis of bromomethane
芬克尔斯坦反应,伴随构型翻转
Finkelstein reaction with inversion
制备腈,碳链增长一个碳
Nitrile synthesis, adding one carbon to the chain
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
瓦尔登发现构型翻转
Walden discovers inversion of configuration
- 1935
休斯与英戈尔德提出 SN2 概念
Hughes and Ingold define SN2
- 1937
英戈尔德等以放射性碘交换实验证实每次取代伴随一次翻转
Ingold and co-workers use radio-iodide exchange to show each substitution causes one inversion