Dr. Manal Fawzy Abou Taleb Organic Chemistry, 7 th Edition L. G. Wade, Jr. Alkyl Halides: Nucleophilic Substitution and Elimination

Alkyl Halides Introduction Nomenclature of Alkyl Halides Physical Properties of Alkyl Halides Preparation of Alkyl Halides Reactions of Alkyl Halides Nucleophilic Substitution Reactions Elimination Reactions Uses 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: RCH 2 F < RCH 2 Cl < RCH 2 Br < RCH 2 I ∵ 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

Solubility 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 Why Alkyl halides have higher melting point than the corresponding alkanes, alkenes, and alkynes because: 1. Polarity 2. Molecular weight

Preparation of Halogeno-compounds Preparation of Haloalkanes Prepared by substituting –OH group of alcohols with halogen atoms Common reagents used: HCl, HBr, HI, PCl 3 or PBr 3 The ease of substitution of alcohols: 3° alcohol > 2° alcohol > 1° alcohol > CH 3 OH This is related to the stability of the reaction intermediate (i.e. stability of carbocations) Substitution of Alcohols

Preparation of Halogeno-compounds Dry HCl is bubbled through alcohols in the presence of ZnCl 2 catalyst Reaction with Hydrogen Halides (HX) For the preparation of bromo- and iodoalkanes, no catalyst is required

Preparation of Halogeno-compounds The reactivity of hydrogen halides: HI > HBr > HCl e.g.

Preparation of Halogeno-compounds Haloalkanes can be prepared from the vigorous reaction between cold alcohols and phosphorus(III) halides Reaction with Phosphorus Halides

Addition of Thionyl Chloride to Alcohols

20 Preparing Alkyl Halides from Alkanes: Radical Halogenation Alkane + Cl 2 or Br 2, 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

Preparation of Halogeno-compounds Addition of Alkenes and Alkynes Alkyl dihalides are prepared from anti addition of bromine (Br 2 ) or chlorine (Cl 2 ) (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.

Preparation of Halogeno-compounds Preparation of Halobenzenes Benzene reacts readily with chlorine and bromine in the presence of catalysts (e.g. FeCl 3, FeBr 3, AlCl 3 ) Halogenation of Benzene

Check Point 32-2 State the major products of the following reactions: (a)CH 3 CHOHCH 2 CH 3 + PBr 3  (b)CH 3 CH = CH 2 + HBr  (c)CH 3 C  CH + 2HBr  Answer Preparation of Halogeno-compounds (a)CH 3 CHBrCH 2 CH 3 (b)CH 3 CHBrCH 3 (c)CH 3 CBr 2 CH 3

Reactions of Halogeno-compounds Carbon-halogen bond is polar Carbon atom bears a partial positive charge Halogen atom bears a partial negative charge

Reactions of Halogeno-compounds Characteristic reaction: Nucleophilic substitution reaction Alcohols, ethers, esters, nitriles and amines can be formed by substituting – OH, – OR, RCOO –, – CN and – NH 2 groups respectively Nu= OH, OR, OCOR, NH 2, RNH, SH, SR, RC=C, CN, X ’

Reactions of Halogeno-compounds 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 HaloalkaneBaseAlkene

a- Formation of Grignard reagent Reaction of Grignared reagent b- Reaction of Grignard reagent

Nucleophilic Substitution Reactions The reactions proceed in 2 different reaction mechanisms: bimolecular nucleophilic substitution (S N 2) unimolecular nucleophilic substitution (S N 1) Reaction with Sodium Hydroxide

Rate = k[CH 3 Cl][OH – ] Nucleophilic Substitution Reactions Example: CH 3 – Cl + OH –  CH 3 OH + Cl – Bimolecular Nucleophilic Substitution (S N 2) 4.9  10 –7 9.8  10 –  10 – Initial rate (mol dm –3 s –1 ) Initial [OH – ] (mol dm –3 ) Initial [CH 3 Cl] (mol dm –3 ) Experiment number Results of kinetic study of reaction of CH 3 Cl with OH – Order of reaction = 2  both species are involved in rate determining step

Nucleophilic Substitution Reactions Reaction mechanism of the S N 2 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

Nucleophilic Substitution Reactions Energy profile of the reaction of CH 3 Cl and OH - by S N 2 mechanism Transition state involve both the nucleophile and substrate  second order kinetics of the reaction

Nucleophilic Substitution Reactions The nucleophile attacks from the backside of the electropositive carbon centre The configuration of the carbon atom under attack inverts Stereochemistry of S N 2 Reactions

Nucleophilic Substitution Reactions Example: Unimolecular Nucleophilic Substitution (S N 1) The rate is independent of [OH – ] Order of reaction = 1  only 1 species is involved in the rate determining step Rate = k[(CH 3 ) 3 CCl] Kinetic study shows that:

Nucleophilic Substitution Reactions Reaction mechanism of S N 1 reaction involves 2 steps and 1 intermediate formed Step 1: Slowest step (i.e. rate determining step) Formation of carbocation and halide ion

Nucleophilic Substitution Reactions 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 (CH 3 ) 3 CCl and OH - by S N 1 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

32.6 Nucleophilic Substitution Reactions (SB p.184) The carbocation formed has a trigonal planar structure The nucleophile may either attack from the frontside or the backside Stereochemistry of S N 1 Reactions

Nucleophilic Substitution Reactions For some cations, different products may be formed by either mode of attack e.g. The reaction is called racemization

Nucleophilic Substitution Reactions The above S N 1 reaction leads to racemization ∵ formation of trigonal planar carbocation intermediate

Nucleophilic Substitution Reactions 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

Nucleophilic Substitution Reactions 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

Nucleophilic Substitution Reactions Delocalized electrons repel any approaching nucleophiles  unreactive towards S N 2 reactions Benzene cations are highly unstable because of loss of aromaticity  unreactive towards S N 1 reactions

Reaction with Potassium Cyanide e.g. Nucleophilic Substitution Reactions 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 32.6 Nucleophilic Substitution Reactions (SB p.194) 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 Ammonia 32.6 Nucleophilic Substitution Reactions (SB p.195) 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