《有机化学》课程教学课件（Organic Chemistry, Alex Jonathan Roche lecture notes Rutgers The State University NJ, wade 8th）Chapter 06 Alkyl Halides

Alkyl Halides Alkyl halides are a class of compounds where a halogen atom or atoms are bound to an sp'orbital of an alkyl group. CHCl (Chloroform:organic solvent) CF,Cl2 (Freon-12:refrigerant CFC) CF,CHCIBr(Halothane:anesthetic) Halogen atoms are more electronegative than carbon atoms,and so the C-Hal bond is polarized. A 6+6 HC一C H The C-X bond is polarized in such a way that there is partial positive charge on the carbon and partial negative charge on the halogen. Ch06 Alkyl Halides (landscape) Page I

Ch06 Alkyl Halides (landscape) Page 1 Alkyl Halides Alkyl halides are a class of compounds where a halogen atom or atoms are bound to an sp3 orbital of an alkyl group. CHCl3 (Chloroform: organic solvent) CF2Cl2 (Freon-12: refrigerant CFC) CF3CHClBr (Halothane: anesthetic) Halogen atoms are more electronegative than carbon atoms, and so the C-Hal bond is polarized. The C-X bond is polarized in such a way that there is partial positive charge on the carbon and partial negative charge on the halogen

Dipole moment 夕 The dipole moment(u)is given in debyes(D): H7* μ=4.8×6×d where 6 is the amount of charge separation, and d is the bond length. Electronegativities decrease in the order of: F>Cl>Br>I Carbon-halogen bond lengths increase in the order of: C-F<C-CI<C-Br<C-I Bond Dipole Moments decrease in the order of: C-CI C-F C-Br C-I μ=1.56D 1.51D1.48D 1.29D Typically the chemistry of alkyl halides is dominated by this effect,and usually results in the C-X bond being broken (either in a substitution or elimination process). This reactivity makes alkyl halides useful chemical reagents Ch06 Alkyl Halides (landscape) Page 2

Ch06 Alkyl Halides (landscape) Page 2 Dipole moment Electronegativities decrease in the order of: F > Cl > Br > I Carbon-halogen bond lengths increase in the order of: C-F C-F > C-Br > C-I  = 1.56D 1.51D 1.48D 1.29D Typically the chemistry of alkyl halides is dominated by this effect, and usually results in the C-X bond being broken (either in a substitution or elimination process). This reactivity makes alkyl halides useful chemical reagents

Nomenclature According to IUPAC,alkyl halides are treated as alkanes with a halogen substituent. The halogen prefixes are Fluoro-,Chloro-,Bromo-and lodo-. Examples: F-CH2CH3 H 、CHs ci H fluoroethane trans-1-chloro-3-methylcyclopentane Often compounds of CH2X2 type are called methylene halides.(CH2Cl2 is methylene chloride). CHX,type compounds are called haloforms.(CHI,is iodoform). CX type compounds are called carbon tetrahalides.(CF is carbon tetrafluoride). Alkyl halides can be primary (1),secondary(2)or tertiary (3). H R R-X R- -X R- H H R 10 20 Other types: A geminal(gem)dihalide has two halogens on the same carbon. A vicinal dihalide has halogens on adjacent carbon atoms. BrBr CI CI RR R-R RR gem-dibromide vicinal dichloride Ch06 Alkyl Halides (landscape) Page 3

Ch06 Alkyl Halides (landscape) Page 3 Nomenclature According to IUPAC, alkyl halides are treated as alkanes with a halogen substituent. The halogen prefixes are Fluoro-, Chloro-, Bromo- and Iodo-. Examples: Often compounds of CH2X2 type are called methylene halides. (CH2Cl2 is methylene chloride). CHX3 type compounds are called haloforms. (CHI3 is iodoform). CX4 type compounds are called carbon tetrahalides. (CF4 is carbon tetrafluoride). Alkyl halides can be primary (1°), secondary (2°) or tertiary (3°). Other types: A geminal (gem) dihalide has two halogens on the same carbon. A vicinal dihalide has halogens on adjacent carbon atoms. F CH2CH3 Cl H H CH3 fluoroethane trans-1-chloro-3-methylcyclopentane R H H X 1 o R R H X 2 o R R R X 3 o R Br Br R gem-dibromide R R Cl R Cl R vicinal dichloride

Preparation of Alkyl Halides Numerous ways to make alkyl halides (la)Free Radical Halogenation Usually this method gives mixtures of mono-,di-,tri-etc halogenated compounds,which is considered an inefficient method for the synthesis of a desired compound. Consider propane: 入+ch2hvCH-Ct-C比Cl+_CHgCHCL-CHa CH3-CH2-CHCl2 +CH3-CCl2-CH3 and others Sometimes if there can be control over the selectivity of halogenation this is a useful route. 以 Cl hv Chlorocyclohexane (50%) CH3 CH3 H3C- H +Br2 hv H3C Br CH3 CH3 t-Butylbromide (90%) Ch06 Alkyl Halides (landscape) Page 4

Ch06 Alkyl Halides (landscape) Page 4 Preparation of Alkyl Halides Numerous ways to make alkyl halides. (1a) Free Radical Halogenation Usually this method gives mixtures of mono-, di-, tri- etc halogenated compounds, which is considered an inefficient method for the synthesis of a desired compound. Consider propane: Sometimes if there can be control over the selectivity of halogenation this is a useful route. + Cl2 h CH3 -CH2 -CH2Cl + CH3 -CHCl-CH3 CH3 -CH2 -CHCl2 +CH3 -CCl2 -CH3 and others H Cl + Cl2 h Chlorocyclohexane (50%) H H CH3 H3C CH3 H + Br2 h CH3 H3C CH3 Br t-Butylbromide (90%)

(1b)Allylic Bromination (Allylic means adjacent to a C=C double bond) The bromination of cyclohexene produces a high yield of 3-bromocyclohexene. allylie positions allylic hydrogens HH H Br HBr cyclohexene 3-bromocyclohexene (80%) An allylic hydrogen has been substituted for a bromine. The bromine atom abstracts an allylic hydrogen because the allylic radical is resonance stabilized abstraction of allylic H cyclohexene allylic radica allylic bromide 620 The radical then reacts with a bromine molecule to continue the chain. Ch06 Alkyl Halides (landscape) Page 5

Ch06 Alkyl Halides (landscape) Page 5 (1b) Allylic Bromination (Allylic means adjacent to a C=C double bond) The bromination of cyclohexene produces a high yield of 3-bromocyclohexene. An allylic hydrogen has been substituted for a bromine. The bromine atom abstracts an allylic hydrogen because the allylic radical is resonance stabilized. The radical then reacts with a bromine molecule to continue the chain

A common reagent for these allylic brominations is N-bromosuccinamide (NBS)because it continually generates small amounts of Br2 through reaction with HBr. H-Br I-H +Br-Br Other methods for Preparation (These will be covered in detail in appropriate later chapters). From alkenes and alkynes: X-x -C=C- 2H-X_ 一C=C一 2X-X Ch06 Alkyl Halides (landscape) Page 6

Ch06 Alkyl Halides (landscape) Page 6 A common reagent for these allylic brominations is N-bromosuccinamide (NBS) because it continually generates small amounts of Br2 through reaction with HBr. Other methods for Preparation (These will be covered in detail in appropriate later chapters). From alkenes and alkynes: N-Br O O + H-Br N-H O O + Br-Br C C C C C H C X H-X C C C X C X X-X C H H C X X 2 H-X C C C X X C X X 2 X-X

From alcohols: R-OH HX.R-X From other halides R-X +X →R-X+X Reactions of Alkyl Halides The alkyl halides are chemically versatile. The halogen atom may leave with its bonding pair of electrons to give a halide ion which is stable-a halide is called a good leaving group If an atom replaces the halide the overall reaction is a substitution. If the halide loss is accompanied by the loss of another atom,the overall reaction is called an elimination Very often the other atom lost is a hydrogen(as H).The elimination of H-X is common,and is called a dehydrohalogenation. Often substitution and elimination reactions will occur in competition with each other. Ch06 Alkyl Halides (landscape) Page 7

Ch06 Alkyl Halides (landscape) Page 7 From alcohols: From other halides: Reactions of Alkyl Halides The alkyl halides are chemically versatile. The halogen atom may leave with its bonding pair of electrons to give a halide ion which is stable – a halide is called a good leaving group. If an atom replaces the halide the overall reaction is a substitution. If the halide loss is accompanied by the loss of another atom, the overall reaction is called an elimination. Very often the other atom lost is a hydrogen (as H+ ). The elimination of H-X is common, and is called a dehydrohalogenation. Often substitution and elimination reactions will occur in competition with each other. R OH H-X R X R X' + X R X - + 'X -

Nucleophilic Substitution H:X: Nuc The nucleophile Nuc:displaces the leaving group X from the carbon atom by using its lone pair to form a new bond to the carbon atom. Elimination A new nt bond is formed by the elimination of halide ion and another atom(usually H) -C-+B:→ B-H +C=C H:X: In a dehydrohalogenation,the base(B:)abstracts a proton from the alkyl halide Most nucleophiles can also act as bases,therefore the preference for elimination or substitution depends on the reaction conditions and the alkyl halide used. Ch06 Alkyl Halides (landscape) Page 8

Ch06 Alkyl Halides (landscape) Page 8 Nucleophilic Substitution The nucleophile Nuc:- displaces the leaving group X￾from the carbon atom by using its lone pair to form a new bond to the carbon atom. Elimination A new  bond is formed by the elimination of halide ion and another atom (usually H+ ). In a dehydrohalogenation, the base (B:- ) abstracts a proton from the alkyl halide. Most nucleophiles can also act as bases, therefore the preference for elimination or substitution depends on the reaction conditions and the alkyl halide used

The SN2 reaction SN2 means substitution nucleophilic bimolecular. Consider the reaction of hydroxide ion with methyl iodide,to yield methanol. H H H0:+ H H一O一C—H+ H H hydroxide iodomethane methanol iodide (nucleophile) (substrate) (product) (leaving group) The hydroxide ion is a good nucleophile since the oxygen atom has a negative charge and a pair of unshared electrons The carbon atom is electrophilic since it is bound to a(more electronegative)halogen,which pulls electron density away from the carbon,thus polarizing the bond with carbon bearing partial positive charge and the halogen bearing partial negative charge. The nucleophile is attracted to the electrophile by electrostatic charges The nucleophile attacks the electrophilic carbon through donation of 2 electrons. Carbon can only have a maximum of 8 valence electrons,so as the carbon-nucleophile bond is forming,then the carbon-leaving group bond must be breaking. lodide is the leaving group since it leaves with the pair of electrons that once bound it to carbon. Ch06 Alkyl Halides (landscape) Page 9

Ch06 Alkyl Halides (landscape) Page 9 The SN2 reaction SN2 means substitution nucleophilic bimolecular. Consider the reaction of hydroxide ion with methyl iodide, to yield methanol. The hydroxide ion is a good nucleophile since the oxygen atom has a negative charge and a pair of unshared electrons. The carbon atom is electrophilic since it is bound to a (more electronegative) halogen, which pulls electron density away from the carbon, thus polarizing the bond with carbon bearing partial positive charge and the halogen bearing partial negative charge. The nucleophile is attracted to the electrophile by electrostatic charges. The nucleophile attacks the electrophilic carbon through donation of 2 electrons. Carbon can only have a maximum of 8 valence electrons, so as the carbon-nucleophile bond is forming, then the carbon-leaving group bond must be breaking. Iodide is the leaving group since it leaves with the pair of electrons that once bound it to carbon

H H0: H0-C- H HH H H nucleophile electrophile transition state product leaving (substrate) group The reaction is said to be concerted,taking place in a single step with the new bond forming as the old bond is breaking. The transition state is a point of highest energy(not an intermediate). H HO- HH 」transition state HO H H reaction coordinate→ Ch06 Alkyl Halides (landscape) Page 10

Ch06 Alkyl Halides (landscape) Page 10 The reaction is said to be concerted, taking place in a single step with the new bond forming as the old bond is breaking. The transition state is a point of highest energy (not an intermediate)