Substitution and Elimination Reaction of Alkyl Halides Organic

Substitution and Elimination Reaction of Alkyl Halides

Organic compounds with an electronegative atom or an electron-withdrawing group bonded to a sp 3 carbon undergo substitution or elimination reactions st b u S n io tut i Elim ina tio n Halide ions are good leaving groups. Substitution reaction on these compounds are easy and are used to get a wide variety of compounds alkyl fluoride alkyl chloride alkyl bromide alkyl iodide

Alkyl Halides in Nature Synthesized by red algae Synthesized by sea hare a sea hare

sea hare

Alkyl Halides in Nature • Several marine organisms, including sponges, corals, and algae, synthesize organohalides (halogen-containing organic compounds) that they use to deterpredators. For example, red algae synthesize a toxic, foultastingorganohalide that keeps predators from eating them. One predator, however, that is not deterred is a mollusk called a sea hare.

Alkyl Halides in Nature • After consuming red algae, a sea hare converts the original organohalide into a structurally similar compound it uses for its own defense. Unlike other mollusks, a sea hare doesnot have a shell. Its method of defense is to surround itself with a slimy material that contains the organohalide, thereby protecting itself from carnivorous fish.

Substitution Reaction with Halides (1) bromomethane If concentration of (1) is doubled, the rate of the reaction is doubled. If concentration of (2) is doubled, the rate of the reaction is doubled. (2) methanol If concentration of (1) and (2) is doubled, the rate of the reaction quadruples.

Substitution Reaction with Halides (1) (2) bromomethane methanol Rate law: rate = k [bromoethane][OH-] this reaction is an example of a SN 2 reaction. S stands for substitution N stands for nucleophilic 2 stands for bimolecular

Mechanism of SN 2 Reactions Alkyl halide The rate of reaction depends on the concentrations of both reactants. When the hydrogens of bromomethane are replaced with methyl groups the reaction rate slow down. The reaction of an alkyl halide in which the halogen is bonded to an asymetric center leads to the formation of only one stereoisomer Relative rate 1200 40 1 ≈0

Mechanism of SN 2 Reactions Hughes and Ingold proposed the following mechanism: Transition state Increasing the concentration of either of the reactant makes their collision more probable.

Mechanism of SN 2 Reactions Steric effect Energy activation energy: DG 2 activation energy: DG 1 reaction coordinate Inversion of configuration (R)-2 -bromobutane (S)-2 -butanol

Factor Affecting SN 2 Reactions The leaving group - + RCH I 2 HO HO + RCH 2 Br + RCH 2 Cl + RCH 2 F - RCH 2 OH + I RCH 2 OH + Br RCH 2 OH + Cl RCH 2 OH + F relative rates of reaction 30 000 10 000 200 1 p. Ka HX -10 -9 -7 3. 2 The nucleophile In general, for halogen substitution the strongest the base the better the nucleophile. p. Ka Nuclephilicity

SN 2 Reactions With Alkyl Halides an alcohol a thiol an ether a thioether an amine an alkyne a nitrile

Substitution Reactions With Halides 1 -bromo-1, 1 -dimethylethane If concentration of (1) is doubled, the rate of the reaction is doubled. If concentration of (2) is doubled, the rate of the reaction is not doubled. 1, 1 -dimethylethanol Rate law: rate = k [1 -bromo-1, 1 -dimethylethane] this reaction is an example of a SN 1 reaction. S stands for substitution N stands for nucleophilic 1 stands for unimolecular

Mechanism of SN 1 Reactions Alkyl halide Relative rate The rate of reaction depends on the concentrations of the alkyl halide only. ≈0* When the methyl groups of 1 -bromo-1, 1 -dimethylethane are replaced with hydrogens the reaction rate slow down. ≈0* The reaction of an alkyl halide in which the halogen is bonded to an asymetric center leads to the formation of two stereoisomers 12 1 200 000 * a small rate is actually observed as a result of a SN 2

Mechanism of SN 1 Reactions nucleophile attacks the carbocation slow C-Br bond breaks fast Proton dissociation

Mechanism of SN 1 Reactions Rate determining step DG Carbocation intermediate R++ X+ R-OH 2 R-OH

Mechanism of SN 1 Reactions Inverted configuration relative the alkyl halide Same configuration as the alkyl halide

Factor Affecting SN 1 reaction Two factors affect the rate of a SN 1 reaction: • The ease with which the leaving group dissociate from the carbon • The stability of the carbocation The more the substituted the carbocation is, the more stable it is and therefore the easier it is to form. As in the case of SN 2, the weaker base is the leaving group, the less tightly it is bonded to the carbon and the easier it is to break the bond The reactivity of the nucleophile has no effect on the rate of a SN 1 reaction

Comparison SN 1 – SN 2 SN 1 SN 2 A two-step mechanism A one-step mechanism A unimolecular rate-determining step A bimolecular rate-determining step Products have both retained and inverted configuration relative to the reactant Product has inverted configuration relative to the reactant Reactivity order: 3 o > 2 o > 1 o > methyl Reactivity order: methyl > 1 o > 2 o > 3 o

Elimination Reactions 1 -bromo-1, 1 -dimethylethane 2 -methylpropene Rate law: rate = k [1 -bromo-1, 1 -dimethylethane][OH-] this reaction is an example of a E 2 reaction. E stands for elimination 2 stands for bimolecular

The E 2 Reaction A proton is removed Br- is eliminated The mechanism shows that an E 2 reaction is a one-step reaction

Elimination Reactions 1 -bromo-1, 1 -dimethylethane If concentration of (1) is doubled, the rate of the reaction is doubled. If concentration of (2) is doubled, the rate of the reaction is not doubled. 2 -methylpropene Rate law: rate = k [1 -bromo-1, 1 -dimethylethane] this reaction is an example of a E 1 reaction. E stands for elimination 1 stands for unimolecular

The E 1 Reaction The base removes a proton The alkyl halide dissociate, forming a carbocation The mechanism shows that an E 1 reaction is a two-step reaction

Products of Elimination Reaction 30% 2 -bromobutane 50% 80% 2 -butene 20% 1 -butene The most stable alkene is the major product of the reaction for both E 1 and E 2 reaction For both E 1 and E 2 reactions, tertiary alkyl halides are the most reactive and primary alkyl halides are the least reactive The greater the number of alkyl substituent the more stable is the alkene

Competition Between SN 2/E 2 and SN 1/E 1 SN 2 E 1 E 2 rate = k 1[alkyl halide] + k 2[alkyl halide][nucleo. ] + k 3[alkyl halide] + k 2[alkyl halide][base] • SN 2 and E 2 are favoured by a high concentration of a good nucleophile/strong base • SN 1 and E 1 are favoured by a poor nucleophile/weak base, because a poor nucleophile/weak base disfavours SN 2 and E 2 reactions

Competition Between Substitution and Elimination • SN 2/E 2 conditions: In a SN 2 reaction: 1 o > 2 o > 3 o In a E 2 reaction: 3 o > 2 o > 1 o 10% 90% 75% 25% 100%

Competition Between Substitution and Elimination • SN 1/E 1 conditions: All alkyl halides that react under SN 1/E 1 conditions will give both substitution and elimination products (≈50%/50%)

Summary • Alkyl halides undergo two kinds of nucleophilic subtitutions: SN 1 and SN 2, and two kinds of elimination: E 1 and E 2. • SN 2 and E 2 are bimolecular one-step reactions • SN 1 and E 1 are unimolecular two step reactions • SN 1 lead to a mixture of stereoisomers • SN 2 inverts the configuration od an asymmetric carbon • The major product of a elimination is the most stable alkene • SN 2 are E 2 are favoured by strong nucleophile/strong base • SN 2 reactions are favoured by primary alkyl halides • E 2 reactions are favoured by tertiary alkyl halides