第 七 章 卤代烃 Halohydrocarbon

1. 第七章 卤代烃Halohydrocarbon 有机化学 Organic Chemistry 教材:徐寿昌 主编 高等教育出版社

2. Teaching contents • Classification of Halogen-Substituted Hydrocarbons (TO) • Nomenclature of Halogen-Substituted Hydrocarbons (TO) • Preparation of Halogen-Substituted Hydrocarbons (TO) • Structure of Halogen-Substituted Hydrocarbons (TO) • Chemical Properties of Halogen-Substituted Hydrocarbons (TO)

3. Classification of Halogen-Substituted Hydrocarbons • The compound that one (or more) hydrogen atom in a hydro-carbon is substituted by halogen atom is called halogen-substituted hydrocarbon. • According to the hydrocarbon, halogen-substituted hydrocarbon can be classified into: • Alkyl halogen, alkenyl halogen, alkynyl halogen, aryl halogen. • According to the degree of carbon, halogen-substituted hydro-carbon can be classified into: primary secondary tertiary halide halide halide

4. Nomenclature of Halogen-Substituted Hydrocarbons(1) • Alkyl halides are named in the same way as alkanes, by treating the halogen as a substituent on a parent alkane chain. There are three rules: • Rule 1 Find the longest carbon chain and name it as the parent. If a double or triple bond is present, the parent chain must contain it. • Rule 2 Number the carbon atoms of the parent chain, beginning at the end nearer the first substituent, regardless of whether it is alkyl or halo. Assign each substituent a number to its position on the chain. • Rule 3 If the parent chain can be properly numbered from either end by rule 2, begin at the end nearer the substituent (either alkyl or halo) that has alphabetical precedence.

5. Preparation of Halogen-Substituted Hydrocarbons • For example: • 2－甲基－5－氯己烷 BACK

6. Preparation of Halogen-Substituted Hydrocarbons (1) • Free radical substitution of alkane • Additions of small cycloalkanes • Addition of Halogens to Alkenes • Hydrohalogenation of Alkenes

7. Preparation of Halogen-Substituted Hydrocarbons (2) • Hydrohalogenation of Alkynes • Free Radical Substitution of Alkenes • Aromatic Halogenation • Bromination of Alkylbenzene Side Chains

8. Preparation of Halogen-Substituted Hydrocarbons (3) • Preparing Alkyl Halides from Alcohols • The most general method for preparing alkyl halides is to make them from alcohols. The simplest method for converting an alcohol to an alkyl halide involves treating the alcohol with HCl, HBr, or HI. • Primary and secondary alcohols are best converted into alkly halides by treatment with such reagents as thionyl chloride (SOCl2) or phosphorus tribromide (PBr3). • BACK

9. Structure of Halogen-Substituted Hydrocarbons (1) • The structure of alkyl halides • The carbon-halogen bond in an alkyl halide results from the overlap of a carbon sp3 orbital with a halogen orbital. Thus, alkyl halides carbon atoms have an approximately tetrahedral geometry. Since halogens are more electro-negative than carbon. The C-X bond is therefore polar, with the carbon atom bearing a slight positive charge (δ+) and the halogen a slight negative charge (δ-).

10. Structure of Halogen-Substituted Hydrocarbons (2) • The structure of vinylic halides and aryl halides • p, π-conjugated system in vinylic halides and aryl halides BACK

11. Chemical Properties of Halogen-Substituted Hydrocarbons (1) • Nucleophilic Substitutions of Alkyl Halides (TO) • TheSN2Reaction and SN1 Reaction (TO) • Elimination Reactions of Alkyl Halides (TO) • Reactions of Halides: Grignard Reagents (TO) • Organometallic Coupling Reactions (TO) • Nucleophilic Aromatic Substitutions (TO) • Benzyne---Elemination/Addition mechanism (TO) • Reactions of Allyl Halides and Benzyl Halides (TO)

12. Chemical Properties of Halogen-Substituted Hydrocarbons (2) • Nucleophilic Substitutions of Alkyl Halides • Alkyl halides can undergo substitution of the X group by the nucleophile (Nu):

13. Chemical Properties of Halogen-Substituted Hydrocarbons (3) For example: NEXT

14. Chemical Properties of Halogen-Substituted Hydrocarbons (4) • TheSN2Reaction • In every chemical reaction, there is a direct relationship between reaction rate and reactant concentrations. When we measure this relationship, wemeasure thekinetics(动力学）of the reaction. For example, let’s look at the kinetics of a simple nucleophilic substitution of CH3Br with OH- to yield CH3OH plus Br -. • This equation says that the rate of disappearance of reactant is equal to a constant of k times the alkyl halide concentration times the hydroxide ion concentration. So the rate of this reaction is dependent on the concentrations of two species, and the reaction issecond-orderreaction.

15. Chemical Properties of Halogen-Substituted Hydrocarbons (5) • TheSN2Reaction • The essential feature of theSN2mechanism is that the reaction takes place in a single step without intermediates. For example: • This reaction occurs through a transition state in which the new HO-C bond is partially forming at the same time that the old C-Br is partially breaking. The transition state for this inversion has the remaining three bonds to carbon in a planar arrangement. The stereochemistry at carbon is inverted. ( Walden Inversion, 沃尔顿翻转)

16. Chemical Properties of Halogen-Substituted Hydrocarbons (6) • TheSN1 Reaction • We might expect that the reaction of a tertiary substrate (hindered) with water to be the slowest of substitution reactions. Remarkably, however, the opposite is true. • What happened? Clearly, these reactions can’t be taking place by theSN2mechanism we have been discussing. This alternative mechanism is called theSN1reaction.

17. Chemical Properties of Halogen-Substituted Hydrocarbons (7) • The reaction of (CH3)3CBr with H2O looks analogous to the reaction of CH3Br with OH-, and we might therefore expect to observe second-order kinetics. In fact, we do not. • We find instead that the reaction rate is dependent only on the alkyl halide concentration and is independent of the H2O concentration. In other words, the reaction is a first-order process.

18. Chemical Properties of Halogen-Substituted Hydrocarbons (8) The mechanism of the reaction of 2-bromo-2-methylpropane with H2O:

19. Chemical Properties of Halogen-Substituted Hydrocarbons (9) • Stereochemistry of the SN1 Reaction: • Since an SN1 reaction occurs through a carbocation intermediate, its stereochemical outcome should be different from that for an SN2 reaction. Since carbocations are planar and are achiral. The carbocation intermediate can be attacked by a nucleophile equally well from either side, leading to a 50:50 mixture of enantiomers – a racemic mixture. For example:

20. Chemical Properties of Halogen-Substituted Hydrocarbons (10) • The factors that effect theSN1 and SN2 reactions NEXT

21. Chemical Properties of Halogen-Substituted Hydrocarbons (11) • Elimination Reactions of Alkyl Halides • When a nucleophile/Lewis base reacts with an alkyl halide, the nucleophile can attack at a neighboring hydrogen and cause elimination of HX to form an alkene.

22. Chemical Properties of Halogen-Substituted Hydrocarbons (12) • Regiochemistry of Elimination of Alkyl Halides- Zaitsev’s Rule • What products result from loss of HX from an unsymmetrical halide? According to a rule of formulated in 1875 by the Russian chemist Alexander Zaitsev, base-induced elimination reactions generallygive the more highly substituted (more stable) alkene product. For example: • The reaction gives mixtures of butene products because elimination reactions can take place through two different mechanistic pathways: the E1and E2 reactions.

23. Chemical Properties of Halogen-Substituted Hydrocarbons (13) • The E2Reaction • The E2 reaction (for elimination, bimolecular) occurs when an alkyl halide is treated with a strong base, such as hydroxide ion or alkoxide ion (RO-). It is the most commonly occurring pathway for elimination and can be formulated as shown below: • Like the SN2 reaction, the E2 reaction takes place in one step without intermediate. As the attacking base begins to abstract H+ from a carbon next the leaving group, the C-H bond begins to break, a C=C bond begins to form, and the leaving group begins to depart, taking with it the electron pair from the C-X bond.

24. Chemical Properties of Halogen-Substituted Hydrocarbons (14) • The stereochemistry of E2 reaction • As shown by a large number of experiments, E2 reactions always occur with a periplanargeometry, meaning that all four reacting atoms-the hydrogen, the two carbons, and the leaving group- lie in the same plane. Two such geometries are possible: syn periplanar geometry, in which the H and X are on the same side of the molecule, and anti periplanargeometry, in which the H and the X are on opposite sides of the molecule. Of the two choices, anti periplanar geometry is energetically preferredbecause it allows the substituents on the two carbons to adopt a staggered relationship, whereas syn geometry requires that the substituents on carbon be eclipsed. For example:

25. Chemical Properties of Halogen-Substituted Hydrocarbons (15) • The E1 Reaction • Just as the E2 Reaction is analogous to the SN2 reaction, there is a close analog to the SN1 reaction called the E1 reaction (for elimination, unimolecular). The E1 reaction can be formulated as shown below:

26. Chemical Properties of Halogen-Substituted Hydrocarbons (16) The factors that effect theE1 andthe E2 reactions NEXT

27. Chemical Properties of Halogen-Substituted Hydrocarbons (17) • Reactions of Halides: Grignard Reagents • Organohalides, RX, react with magnesium metal in dry ether or tetrahydrofuran (THF) solvent to yield organo-magnesium halides, RMgX. The products, called Grignard reagents after their discoverer, Victor Grignard (1912 Nobel Prize winner), are examples of organo-metallic compounds because they contain a carbon-metal bond.

28. Chemical Properties of Halogen-Substituted Hydrocarbons (18) • The reactions of Ethylmagnesium bromide:

29. Chemical Properties of Halogen-Substituted Hydrocarbons (19) • Organometallic Coupling Reactions • Many other kinds of organometallic compounds can be prepared in a manner similar to that of Grignard reagents. For example, alkyllithium reagents, RLi, can be prepared by the reaction of an alkyl halides with lithium metal. For example: • One of the most valuable reactions of alkyllithiums is their use in making lithium diorganocopper compounds, R2CuLi, called Gilman reagents. For example: • Gilman reagents are useful because they undergo organometallic coupling reactions with alkyl halides to yield hydrocarbon product.

30. Chemical Properties of Halogen-Substituted Hydrocarbons (20) • Nucleophilic Aromatic Substitutions • Aromatic substitution reactions usually occur by an electrophilic mechanism. Aryl halides that have electron-withdrawing substituents, however, can also undergo nucleophilic aromatic substitution. For example: • Nucleophilic substitutions on an aromatic ring proceed by the addition /elimination mechanism shown below:

31. Chemical Properties of Halogen-Substituted Hydrocarbons (21) • Benzyne---Elimination/Addition mechanism • Halobenzenes without electron-withdrawing substituents do not react with nucleophiles under most conditions. At high temperature and pressure, however, even chlorobenzene can be forced to react. • Mechanism of reaction:

32. Chemical Properties of Halogen-Substituted Hydrocarbons (22) • Reactions of Allyl Halides and Benzyl Halides