dr. manal fawzy abou taleb organic chemistry, 7 th edition l. g. wade, jr. alkyl halides:...

Dr. Manal Fawzy Abou Taleb

Organic Chemistry, 7th EditionL. G. Wade, Jr.

Alkyl Halides: Nucleophilic Substitution and Elimination

Alkyl HalidesIntroductionIntroduction

Nomenclature of Alkyl HalidesNomenclature of Alkyl Halides

Physical Properties of Alkyl HalidesPhysical Properties of Alkyl Halides

Preparation of Alkyl HalidesPreparation of Alkyl Halides

Reactions of Alkyl HalidesReactions of Alkyl Halides

Nucleophilic Substitution ReactionsNucleophilic Substitution Reactions

Elimination ReactionsElimination Reactions

Uses of Alkyl HalidesUses of Alkyl Halides

Introduction

• Alkyl Halides are organic compounds having one or more halogen atoms bonded to a carbon atom.

What Is an Alkyl Halide

• Identify the longest continuous carbon chain

– It must contain any double or triple bond if present

– Number from end nearest any substituent (alkyl or halogen)

– If any multiple bonds are present, number from end closest to these.

– The halogens are written as prefixes: fluoro- (F), chloro- (Cl), bromo- (Br) and iodo- (I)

IUPAC Nomenclature• Name as haloalkane.

Naming with Multiple Halides

• If more than one of the same kind of halogen is present, use prefix di, tri, tetra

• If there are several different halogens, number them and list them in alphabetical order

Naming if Two Halides or Alkyl Are Equally Distant from Ends of Chain

• Begin at the end nearer the substituent whose name comes first in the alphabet

In case of halobenzenes, the benzene ring is numbered so as to give the lowest possible numbers to the substituents e.g.

7

Systematic Common Names

iso-butyl bromide sec-butyl bromide

Common names are often used for simple alkyl halides. To assign a common name:

Name all the carbon atoms of the molecule as a single alkyl group.

Name the halogen bonded to the alkyl group.

Combine the names of the alkyl group and halide, separating the words with a space.

Many Alkyl Halides That Are Widely Used Have Common Names

• Chloroform

• Carbon tetrachloride

• Methylene chloride

• Methyl iodide

• Trichloroethylene

• A halogen attached to a carbon next to a doubly bonded carbon is an Allylic Halide

A halogen is attached directly to a doubly bonded carbon is called: Vinylic halides

• A halogen one carbon away from an aromatic ring is Benzylic Halide

A halogen attached directly to a benzene ring is an Aryl halide

Halobenzenes are organic compounds in which the halogen atom is directly attached to a benzene ring

e.g.

not a halobenzene, because the chlorine atom is not directly attached to the benzene ring

Classes of alkyl halides• Haloalkanes are classified into primary, secondary and

tertiary, based on the number of alkyl groups attached to the carbon atom which is bonded to the halogen atom

• The boiling points increases with increasing in molecular weights.

m.p. and b.p. increase in the order:

RCH2F < RCH2Cl < RCH2Br < RCH2I

larger, more polarizable halogen atoms increase the ∵

dipole-dipole interactions between the molecules

No. of carbon m.p. and b.p.

Haloalkanes have higher b.p. and m.p. than alkanes∵ dipole-dipole interactions are present between haloalkane molecules

SolubilitySolubility

Although C — X bond is polar, it is not polar enough to have

a significant effect on the solubility of haloalkanes and

halobenzenes

Immiscible with water

Soluble in organic solvents

Explain WhyAlkyl halides have higher melting point than the corresponding alkanes, alkenes, and alkynes because:

1. Polarity 2. Molecular weight

Preparation of Halogeno-compounds

Preparation of HaloalkanesPreparation of Haloalkanes

• Prepared by substituting –OH group of alcohols with halogen atoms

• Common reagents used: HCl, HBr, HI, PCl3 or PBr3

• The ease of substitution of alcohols:3° alcohol > 2° alcohol > 1° alcohol > CH3OH

• This is related to the stability of the reaction intermediate (i.e. stability of carbocations)

Substitution of Alcohols


• Dry HCl is bubbled through alcohols in the presence of ZnCl2 catalyst

Reaction with Hydrogen Halides (HX)

• For the preparation of bromo- and iodoalkanes, no catalyst is required


• The reactivity of hydrogen halides: HI > HBr > HCl

• e.g.


Haloalkanes can be prepared from the vigorous reaction

between cold alcohols and phosphorus(III) halides

Reaction with Phosphorus Halides

R-OH + PX5 or PCl5 R-X

CH3CH2OH + PCl5 2 CH3CH2-Cl + POCl3 + H2O

3 CH3CH2OH + PBr3 3 CH3CH2Br + H3PO3

Reaction with Phosphorus Halides

Addition of Thionyl Chloride to Alcohols

R-OH + SOCl2Pyridine

R-Cl + SO2 + HCl

CH3CH2OH + SOCl2Pyridine

CH3CH2Cl + SO2 + HCl

20

Preparing Alkyl Halides from Alkanes: Radical Halogenation

• Alkane + Cl2 or Br2, heat or light replaces C-H with C-X but gives mixtures– Hard to control– Via free radical mechanism

• It is usually not a good idea to plan a synthesis that uses this method—multiple products


Addition of Alkenes and Alkynes

•Alkyl dihalides are prepared from anti addition of bromine (Br2) or chlorine (Cl2) (addition of halogen)

Addition of Alkenes and Alkynes

The most effective means of preparing an alkyl halide is from addition of HCl, HBr, HI to alkenes or alkyne to give Markovnikov product Anti-Markinikoff’s rule.

CH2 CH2

R-CH CH-R R-CH CH2-R

X

CH3-CH CH2 CH3CH3

Br

CH3-CH CH2 CH3 CH2-CH2-Br

+ HI

+ HX

CH3CH2I

+ HBr CH (Markinikoff rule)

+ HBr (Anti-Markinikoff rule)peroxide


Preparation of HalobenzenesPreparation of Halobenzenes

Benzene reacts readily with chlorine and bromine in the

presence of catalysts (e.g. FeCl3, FeBr3, AlCl3)

Halogenation of Benzene

Check Point 32-2 Check Point 32-2

State the major products of the following reactions:

(a) CH3CHOHCH2CH3 + PBr3

(b) CH3CH = CH2 + HBr

(c) CH3C CH + 2HBr Answer


(a) CH3CHBrCH2CH3

(b) CH3CHBrCH3

(c) CH3CBr2CH3

Reactions of Halogeno-compounds

• Carbon-halogen bond is polar

• Carbon atom bears a partial positive charge

• Halogen atom bears a partial negative charge


• Characteristic reaction:

Nucleophilic substitution reaction

• Alcohols, ethers, esters, nitriles and amines can be

formed by substituting – OH, – OR, RCOO –, – CN

and – NH2 groups respectively

Nu= OH, OR, OCOR, NH2, RNH, SH, SR, RC=C, CN, X’


• Another characteristic reaction:

Elimination reaction

• Bases and nucleophiles are the same kind of reagents

• Nucleophilic substitution and elimination reactions

always occur together and compete each other

Haloalkane Base Alkene

a- Formation of Grignard reagent

R X + Mg Dry ether

R MgX (X=Cl, Br, I)

Ar X Mg Dry ether

Ar MgX (X=Cl, Br, I)+

R MgX

OH2R H + Mg(OH)X

R'OHR H + Mg(OR')X

CH CHR H + Mg(HCC)X

Reaction of Grignared reagent

b- Reaction of Grignard reagent

Nucleophilic Substitution Reactions

The reactions proceed in 2 different reaction

mechanisms:

bimolecular nucleophilic substitution (SN2)

unimolecular nucleophilic substitution (SN1)

Reaction with Sodium HydroxideReaction with Sodium Hydroxide

Rate = k[CH3Cl][OH–]


Example: CH3 – Cl + OH– CH3OH + Cl–

Bimolecular Nucleophilic Substitution (SN2)

4.9 10–7

9.8 10–7

9.8 10–7

19.6 10–7

1.0

1.0

2.0

2.0

0.001

0.002

0.001

0.002

1

2

3

4

Initial rate (mol dm–3 s–1)

Initial [OH–]

(mol dm–3)

Initial [CH3Cl]

(mol dm–3)

Experiment number

Results of kinetic study of reaction of CH3Cl with OH–

Order of reaction = 2 both species are involved in rate determining step


Reaction mechanism of the SN2 reaction:

• The nucleophile attacks from the backside of the electropositive carbon centre

• In the transition state, the bond between C and O is partially formed, while the bond between C and Cl is partially broken


Energy profile of the reaction of CH3Cl and OH- by SN2 mechanism

Transition state involve both the nucleophile and substrate second order kinetics of the reaction


• The nucleophile attacks from the backside of the electropositive carbon centre

• The configuration of the carbon atom under attack inverts

Stereochemistry of SN2 Reactions


Example:

Unimolecular Nucleophilic Substitution (SN1)

• The rate is independent of [OH–]

• Order of reaction = 1 only 1 species is involved in the rate

determining step

Rate = k[(CH3)3CCl]

• Kinetic study shows that:


Reaction mechanism of SN1 reaction involves 2 steps

and 1 intermediate formed

Step 1:

• Slowest step (i.e. rate determining step)

• Formation of carbocation and halide ion


Step 2:

• Fast step

• Attacked by a nucleophile to form the product

32.6 Nucleophilic Substitution Reactions (SB p.183)

Energy profile of the reaction of (CH3)3CCl and OH- by SN1 mechanism

• Rate determining step involves the breaking of the C – Cl bond to form carbocation

• Only 1 molecule is involved in the rate determining step first order kinetics of the reaction


• The carbocation formed has a trigonal planar structure

• The nucleophile may either attack from the frontside or the backside

Stereochemistry of SN1 Reactions


For some cations, different products may be formed by either mode of attack

e.g.

The reaction is called racemization


The above SN1 reaction leads to racemization

∵ formation of trigonal planar carbocation intermediate


The attack of the nucleophile from either side of the planar carbocation occurs at equal rates and results in the formation of the enantiomers of butan-2-ol in equal amounts


• Halobenzenes are comparatively unreactive to nucleophilic substitution reactions

∵ the p orbital on the carbon atom of the benzene ring and that on the halogen atom overlap side-by-side to form a delocalized bonding system

Unreactivity of Halobenzene


• Delocalized electrons repel any approaching

nucleophiles

unreactive towards SN2 reactions

• Benzene cations are highly unstable because of loss

of aromaticity

unreactive towards SN1 reactions

Reaction with Potassium CyanideReaction with Potassium Cyanide

e.g.


A nitrile is formed when a haloalkane is heated under reflux

with an aqueous alcoholic solution of potassium cyanide

• Cyanide ion (CN–) acts as a nucleophile


• Halobenzenes do not react with potassium cyanide

• The reaction is very useful because the nitrile can be hydrolyzed to carboxylic acids which can be reduced to alcohols

• A useful way of introducing a carbon atom into an organic molecule, so that the length of the carbon chain can be increased

Reaction with AmmoniaReaction with Ammonia


When a haloalkane is heated with an aqueous alcoholic solution of ammonia under a high pressure, an amine is formed

e.g.

• Ammonia is a nucleophile because the presence of a

lone pair of electrons on the nitrogen atom

The END

dr. manal fawzy abou taleb organic chemistry, 7 th edition l. g. wade, jr. alkyl halides:...

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