定义Definition
烷基化是把烷基引入分子（连接到碳、氮、氧或硫上）的反应的总称。常用烷基化试剂有卤代烷、硫酸酯、磺酸酯、烯烃（酸催化）和醇。
Alkylation is the general term for introducing an alkyl group onto carbon, nitrogen, oxygen or sulfur. Common alkylating agents are alkyl halides, sulfates and sulfonates, alkenes (acid-catalysed) and alcohols.
主要类型Main types
C-烷基化：傅–克烷基化（芳环）、烯醇负离子烷基化（如乙酰乙酸乙酯、丙二酸酯合成法）、格氏试剂与卤代烃偶联；N-烷基化：胺与卤代烃（易多重烷基化）、还原胺化；O-烷基化：威廉姆森醚合成；S-烷基化：硫醇盐成硫醚。
C-alkylation: Friedel–Crafts (arenes), enolate alkylation (acetoacetic and malonic ester syntheses), coupling of organometallics; N-alkylation: amines with halides (prone to over-alkylation) or reductive amination; O-alkylation: Williamson ether synthesis; S-alkylation: thiolates to thioethers.
工业烷基化Industrial alkylation
炼油中用 HF 或 H₂SO₄ 催化异丁烷与丁烯反应生成高辛烷值的“烷基化油”（异辛烷）；苯与乙烯在沸石催化下生成乙苯（制苯乙烯），苯与丙烯生成异丙苯（制苯酚和丙酮）。
Refineries react isobutane with butenes over HF or H₂SO₄ to make high-octane alkylate (isooctane); benzene + ethylene over zeolites gives ethylbenzene (for styrene), and benzene + propylene gives cumene (for phenol and acetone).
生物学与毒性Biology and toxicity
S-腺苷甲硫氨酸是生物体内的通用甲基化试剂（DNA 甲基化调控基因表达）。烷基化剂（氮芥、环磷酰胺、替莫唑胺）可使 DNA 碱基烷基化，被用作抗癌药，同时也具有致突变性。
S-Adenosylmethionine is the universal biological methyl donor (DNA methylation regulates genes). Alkylating agents (nitrogen mustards, cyclophosphamide, temozolomide) alkylate DNA bases and are anticancer drugs, but are also mutagenic.
反应Reactions
视亲核试剂与烷基化试剂而定
Depends on nucleophile and alkylating agent
生成亲核试剂（去质子化）或亲电试剂（路易斯酸活化）。
Generate the nucleophile (deprotonation) or electrophile (Lewis-acid activation).
SN2 或亲电芳香取代形成新键。
SN2 or electrophilic aromatic substitution forms the bond.
工业制乙苯。
Industrial ethylbenzene.
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
- 1877
傅里德尔与克拉夫茨报道芳环烷基化
Friedel and Crafts report arene alkylation
- 1938
炼油硫酸烷基化工业化
Sulfuric-acid refinery alkylation is commercialised
- 1942
氮芥首次用于癌症治疗
Nitrogen mustard first used in cancer therapy