华南师范大学：《有机化学》精品课程电子教案（双语版）第九章 卤代烃

附件2 粒大浮 教 案 2003~~2004学年第Ⅰ学期 院(系、所、部)化学与环境学院有机化学研究所 教研室有机化学 课程名称有机化学(双语教学) 授课对象化学教育 授课教师杨定乔 职称职务教授 教材名称 Organic Chemistry 2003年09月01日

附件 2 教 案 2003~~ 2004 学年 第 I 学期 院（系、所、部）化学与环境学院有机化学研究所 教 研 室 有机化学 课 程 名 称 有机化学（双语教学） 授 课 对 象 化学教育 授 课 教 师 杨定乔 职 称 职 务 教授 教 材 名 称 Organic Chemistry 2003 年 09 月 01 日

有机化学(双语教学)课程教案 授课题目(教学章节或主题):第九章.卤代烃授课类型理论课 Haloalkanes or Alkyl Halides 第13周第43-46 授课时间 教学目标或要求:了解卤代烃分类,命名及同分异构现象。了解卤代烃的亲核取代反 应历程及其制备。重点掌握卤代烃的亲核取代反应历程(SN1和SN2) 教学内容(包括基本内容、重点、难点) 基本内容包括了解卤代烃分类,命名及同分异构现象。了解卤代烃的亲核取代反应历 程及其制备。重点掌握卤代烃的亲核取代反应历程(SN1和SN2 Nomenclature of Alkyl Halides Simple alkyl halides are named as substituents on the parent alkane, using chioro, bromo, iodo or fluoro to denote the nature of the halogen. 1. First, se lect the longest continuous carbon chain; if the molecule conta ins a double or triple bond, the parent cha in must contain it 2. Num ber the carbon chain in the direction to produce the lowest number for the first substituent encountered, or to give the lowest num ber sequence at the first point of difference 3. Num ber the substituents and write the name, listing substituents alphabetically Several simple examples are shown below: H3C CH3 In the first example, the parent chain is a hexane and a bromine is attached

有机化学(双语教学) 课程教案 授课题目（教学章节或主题）：第九章．卤代烃 （Haloalkanes or Alkyl Halides） 授课类型 理论课 授课时间 第 13 周第 43-46 节 教学目标或要求：了解卤代烃分类，命名及同分异构现象。了解卤代烃的亲核取代反 应历程及其制备。重点掌握卤代烃的亲核取代反应历程（SN1 和 SN2） 教学内容（包括基本内容、重点、难点）： 基本内容包括了解卤代烃分类，命名及同分异构现象。了解卤代烃的亲核取代反应历 程及其制备。重点掌握卤代烃的亲核取代反应历程（SN1 和 SN2）。 Nomenclature of Alkyl Halides Simple alkyl halides are named as substituents on the parent alkane, using chloro, bromo, iodo or fluoro to denote the nature of the halogen. 1. First, select the longest continuous carbon chain; if the molecule contains a double or triple bo nd, the parent chain must contain it. 2. Number the carbon chain in the direction to produce the lowest number for the first substituent encountered, or to give the lowest number sequence at the first point of difference. 3. Number the substituents and write the name, listing substituents alphabetically. Several simple examples are shown below: In the first example, the parent chain is a hexane and a bromine is attached

to carbon #3. If we had started numbering at the other end, the bromine would be in position #4; hence the name, 3-bromohexane In the second example, there are two potential five-carbon chains; in this case the chain with the most substituents is selected as parent, (a pentane Attached to the pentane at carbon #2 is a bromo group and at carbon #3, an ethyl group; hence the name 2-bromo-3-ethy pentane In the third example, the iodine is attached to a cyclohexane ring and wil therefore be named as a halocycloalkane; the name is iodocyclohexane (no number required) In the last example, the chlorine and two methyl groups are attached to a cyclopentane ring. The numbering must begin at the carbon bearing the methy l groups since the sequence [1, 1, 2] is lower at the first point of difference than the sequence [1, 2, 2], which you would have if the chlorine was attached to carbon #l; the name is therefore 2-chloro-1, 1-dimethy l cyclopentane Nucleophilic Substitution Reactions As described previously, the carbon-halogen bond in alkyl halides is polarized placing a partial positive charge on the carbon, and a partial negative charge on the halogen. The partially positive carbon is therefore electrophilic and will be susceptible to attack by nucleophiles. When a suitable nucleophile attacks an alkyl halide, it can displace the halogen in a substitution reaction to release the halide anion and form a new bond to the carbon as shown below Leaving gro CH3 Nucleophile With simple primary alky l halides reacting with simple nucleophiles, the rate at which this substitution reaction proceeds is proportional to both the concentration of the nucleophile and the concentration of the reac tant alkyl halide, making the reaction second order. This type of second-order nucleophilic displacement reaction is therefore termed an S,2 reaction (substitution, nucleophilic, bimolecular). The mechanism for this reaction is best described as concerted with the reaction coordinate passing through a single energy maximum with no distinct intermediate. The transition state for

to carbon #3. If we had started numbering at the other end, the bromine would be in position #4; hence the name, 3-bromohexane. In the second example, there are two potential five-carbon chains; in this case, the chain with the most substituents is selected as parent, (a pentane). Attached to the pentane at carbon #2 is a bromo group and at carbon #3, an ethyl group; hence the name 2-bromo-3-ethylpentane. In the third example, the iodine is attached to a cyclohexane ring and will therefore be named as a halocycloalkane; the name is iodocyclohexane (no number required). In the last example, the chlorine and two methyl groups are attached to a cyclopentane ring. The numbering must begin at the carbon bearing the methyl groups since the sequence [1,1,2] is lower at the first point of difference than the sequence [1,2,2], which you would have if the chlorine was attached to carbon #1; the name is therefore 2-chloro-1,1-dimethylcyclopentane. Nucleophilic Substitution Reactions As described previously, the carbon-halogen bond in alkyl halides is polarized, placing a partial positive charge on the carbon, and a partial negative charge on the halogen. The partially positive carbon is therefore electrophilic and will be susceptible to attack by nucleophiles. When a suitable nucleophile attacks an alkyl halide, it can displace the halogen in a substitution reaction to release the halide anion and form a new bond to the carbon, as shown below. With simple primary alkyl halides reacting with simple nucleophiles, the rate at which this substitution reaction proceeds is proportional to both the concentration of the nucleophile and the concentration of the reactant alkyl halide, making the reaction second order. This type of second-order, nucleophilic displacement reaction is therefore termed an "SN2" reaction (substitution, nucleophilic, bimolecular). The mechanism for this reaction is best described as concerted with the reaction coordinate passing through a single energy maximum with no distinct intermediate. The transition state for

this reaction is described by the structure shown below in which partial bond exist between the central carbon and the attacking nucleophile and departing halogen. An animation of S2 Reaction Rate-Limiting this process also appears Br Se R-X Nu R-Nu +X The geometry of this transition state, with the pl anar carbon in the center, requires that the central carbon undergo a stereochemical i nvers ion therefore if the central carbon is chiral, the ab so lute configurat ion of the central carbon must change. In the example shown below, R-2-bromobutane reacts with br om i de anion to form the enant i omer s-2-bromobutane R-2-bromobutane HCH S-2-bromobutane Predicting the product from these types of substitution reactions simply requires that the bond to the halogen leaving group be broken and a new bond be made between the nucleophilic atom and the central carbon, inverting the absolute configuration if appropriate

this reaction is described by the structure shown below in which partial bonds exist between the central carbon and the attacking nucleophile and departing halogen. An animation of this process also appears below. The geometry of this transition state, with the planar carbon in the center, requires that the central carbon undergo a s t ereochemical i nversion; therefore if the central carbon is chiral, the absolute configuration of the central carbon must change. In the example shown below, R-2-bromobutane reacts with bromide anion to form the enantiomer, S -2-bromobutane. Predicting the product from these types of substitution reactions simply requires that the bond to the halogen leaving group be broken and a new bond be made between the nucleophilic atom and the central carbon, inverting the absolute configuration if appropriate

°,RH S,2 reaction mechanisms are also involved in two common procedures which can be utilized to prepare alky l halides from alcohols; that is reaction with PBr and with SoClz In the reaction with PBr,, an intermediate phosphite ester is formed, which undergoes S,2 displacement with bromide anion to give the alkyl bromide with inversion of configuration Br3 a phosphite ester Thiony l chloride reacts by a similar mechanism involving a sulfite ester in polar solvents (i.e, pyridine), but can undergo an unusual S i mechanism in non-polar solvents (benzene) to give the alkyl chloride with retention of configuration (this involves an unusual frontside attack, but is worth remembering since the pair of reactions gives you stereochemical control over the generation of an alkyl chloride)

SN2 reaction mechanisms are also involved in two common procedures which can be utilized to prepare alkyl halides from alcohols; that is reaction with PBr3 and with SOCl2. In the reaction with PBr3, an intermediate phosphite ester is formed, which undergoes SN2 displacement with bromide anion to give the alkyl bromide with inversion of configuration. Thionyl chloride reacts by a similar mechanism involving a sulfite ester in polar solvents (i.e., pyridine), but can undergo an unusual SNi mechanism in non-polar solvents (benzene) to give the alkyl chloride with retention of configuration (this involves an unusual frontside attack, but is worth remembering since the pair of reactions gives you stereochemical control over the generation of an alkyl chloride)

SN2 Displacement SNi Displacement Cl/ with Inversion with retention rAdde alme a sulfite ester a sufite ester Unlike primary alky l halides, when most tertiary alkyl halides react with simple nucleophiles, the rate at which the substitution reaction proceeds is proportional only to the concentration of the alky I halide, making the reaction first order. This type of first-order, nucleophilic displacement reaction is therefore termed an"S, 1"reaction(substitution, nucleophilic, unimolecular The mechanism for this reaction is best described as stepwise with the involvement of a carbocation intermediate. The rate limiting step for this reaction is the spontaneous breaking of the carbon-halogen bond to form the carbocation, and the reaction with the nucleophile is generally fast. Since only the alky l halide is present in the rate-limiting transition state, only alky l halide concentration will effect the rate SHI Reaction Rate-Limiting Since only one reactant is present in the rate- R-X +Nu limiting transition state the rate ll be R-Nu +independent of the rate of Since carbocations are involved, the reaction is prone to rearrangement, which may involve hydride shifts, alkyl group shifts or skeletal rearrangements

Unlike primary alkyl halides, when most tertiary alkyl halides react with simple nucleophiles, the rate at which the substitution reaction proceeds is proportional only to the concentration of the alkyl halide, making the reaction first order. This type of first-order, nucleophilic displacement reaction is therefore termed an "SN1" reaction (substitution, nucleophilic, unimolecular). The mechanism for this reaction is best described as stepwise with the involvement of a carbocation intermediate. The rate limiting step for this reaction is the spontaneous breaking of the carbon-halogen bond to form the carbocation, and the reaction with the nucleophile is generally fast. Since only the alkyl halide is present in the rate-limiting transition state, only alkyl halide concentration will effect the rate. Since carbocations are involved, the reaction is prone to rearrangement, which may involve hydride shifts, alkyl group shifts or skeletal rearrangements

Step 1: Ionization to form 1 H Step 2: 1-2 Hydride shift Step 3: Attack of the brm the more stable3° Nucleophile The most significant factor in determining whether a given substitution reaction will follow an S,I or an S, 2 mechanism is the nature of the reactant the more stable the potential carbocation, the more likely an s,I mechanism becomes. Therefore, primary alkyl halides will generally follow pure pathways, tertiary alky l halides will generally follow S,1 pathways, and secondary alky l halides may follow either, depending on the exact nature of the compound Br一 Reactivity in S2 Reaction 教学手段与方法:课堂讲授,幻灯投影谱图。 思考题、讨论题、作业:第254面. Additional problems;612-6.30 参考资料(含参考书、文献等) 1. Solomons, Organic Chemistry, fifth adition 2. Oxford: Organic Chemistry 3.北京大学,有机化学 4.南京大学,有机化学,(上,下) 5.邢其毅,有机化学,(上,下) 注:1、每项页面大小可自行添减;2一次课为一个教案;3、“重点"、“难点”、“教学手段

The most significant factor in determining whether a given substitution reaction will follow an SN1 or an SN2 mechanism is the nature of the reactant; the more stable the potential carbocation, the more likely an SN1 mechanism becomes. Therefore, primary alkyl halides will generally follow "pure" SN2 pathways, tertiary alkyl halides will generally follow SN1 pathways, and secondary alkyl halides may follow either, depending on the exact nature of the compound. 教学手段与方法：课堂讲授，幻灯投影谱图。 思考题、讨论题、作业：第 254 面. Additional Problems; 6.12-6.30) 参考资料（含参考书、文献等）： 1. Solomons, Organic Chemistry, fifth adition 2. Oxford; Organic Chemistry 3. 北京大学， 有机化学 4．南京大学， 有机化学，（上，下） 5．邢其毅，有机化学， （上，下） 注：1、每项页面大小可自行添减；2 一次课为一个教案；3、“重点”、“难点”、“教学手段

与方法”部分要尽量具体;4、授课类型指:理论课、讨论课、实验或实习课、练习或习题 课等

与方法”部分要尽量具体；4、授课类型指：理论课、讨论课、实验或实习课、练习或习题 课等