Alkyl halides can react with Lewis bases by Alkyl halides can react with Lewis bases by nucleophilic substitution and/or elimination.nucleophilic substitution and/or elimination.

CC CC

HH

XX

++ YY::––

CC CC

YY

HH

XX::––

++

CC CC ++ HH YY XX::––

++

-elimination-elimination

nucleophilic substitutionnucleophilic substitution

Substitution and EliminationSubstitution and Eliminationas Competing Reactionsas Competing Reactions

NucleophilicNucleophiliciity vs. Basicityty vs. Basicity

All Nucleophiles act like Bases and All Nucleophiles act like Bases and vice-versavice-versa..

BaseBase; Ability to accept proton; Ability to accept proton

measured by thermodynamicsmeasured by thermodynamics

NucleophilicityNucleophilicity; ability to cause substitution ; ability to cause substitution reaction (depends on reaction conditions)reaction (depends on reaction conditions)

measured by kineticsmeasured by kinetics

Guidelines for Determining Basicity Guidelines for Determining Basicity and Nucleophilicityand Nucleophilicity

1.1. When the same nucleophilic atom is When the same nucleophilic atom is compared; the anion is both more basic and compared; the anion is both more basic and nucleophilic with respect to the neutral nucleophilic with respect to the neutral molecule.molecule.

OHOH-- More Basic & Nucleophilic More Basic & NucleophilicThan HThan H22OO

RankRank NucleophileNucleophile RelativeRelativerate rate

good good HOHO––, RO, RO–– 101044

fairfair RCORCO22–– 101033

weakweak HH22O, ROHO, ROH 11

When the attacking atom is the same (oxygenWhen the attacking atom is the same (oxygenin this case), nucleophilicity increases with in this case), nucleophilicity increases with increasing basicity.increasing basicity.

Table 8.4 NucleophilicityTable 8.4 Nucleophilicity

Guidelines for Determining Guidelines for Determining Basicity and NucleophilicityBasicity and Nucleophilicity

2.2. If the comparison is made in the same If the comparison is made in the same period; both nucleophilicity and basicity period; both nucleophilicity and basicity increase going to the left.increase going to the left.

NHNH22-- > OH > OH-- >F >F--

More Basic and NucleophilicMore Basic and Nucleophilic

Guidelines for Determining Guidelines for Determining Basicity and NucleophilicityBasicity and Nucleophilicity

3.3. If the comparison is made going down a If the comparison is made going down a group; basicity increases going up while group; basicity increases going up while nucleophilicity increases going down.nucleophilicity increases going down.

FF-- Cl Cl-- Br Br-- I I--

Increasing BasicityIncreasing Basicity

Increasing NucleophilicityIncreasing Nucleophilicity

Basicity Trend Down a GroupBasicity Trend Down a Group

AcidAcid Conjugate BaseConjugate Base

HF; weak acidHF; weak acid FF--; strong conj; strong conj.. base base

HCl; strong acidHCl; strong acid ClCl--; weak conj; weak conj.. base base

HBr; strong acidHBr; strong acid BrBr--; weak conj; weak conj.. base base

HI; strong acidHI; strong acid II--; weak conj; weak conj.. base base

Nucleophilicity Trend Down a GroupNucleophilicity Trend Down a Group

SolvationSolvation

– small negative ions are highly small negative ions are highly solvated in protic solventssolvated in protic solvents

– large negative ions are less large negative ions are less solvatedsolvated

– As solvation increases; As solvation increases; nucleophile nucleophile

strength decreasesstrength decreases

RankRank NucleophileNucleophile RelativeRelativeraterate

strongstrong II-- >10>1055

good good BrBr-- 101044

fairfair ClCl--, F, F-- 101033

A tight solvent shell around an ion makes itA tight solvent shell around an ion makes itless reactive. Larger ions are less solvated thanless reactive. Larger ions are less solvated thansmaller ones and are more nucleophilic.smaller ones and are more nucleophilic.

Table 8.4 NucleophilicityTable 8.4 Nucleophilicity

Guidelines for Determining Basicity Guidelines for Determining Basicity and Nucleophilicityand Nucleophilicity

4.4. Steric hinderance decreases nucleophile strength Steric hinderance decreases nucleophile strength and increases base strength.and increases base strength.

OC

-

H

H

H

OC

-C

C

C

H

H

HH

H

H

HH

H

Alkyl halides can react with Lewis bases by Alkyl halides can react with Lewis bases by nucleophilic substitution and/or elimination.nucleophilic substitution and/or elimination.

CC CC

HH

XX

++ YY::––

CC CC

YY

HH

XX::––

++

CC CC ++ HH YY XX::––

++

-elimination-elimination

nucleophilic substitutionnucleophilic substitution

Substitution and EliminationSubstitution and Eliminationas Competing Reactionsas Competing Reactions

Substitution vs. Elimination Substitution vs. Elimination Effect of Alkyl HalideEffect of Alkyl Halide

1° RX1° RX

Formation of carbocation will not happen; rules Formation of carbocation will not happen; rules out E1 or Sout E1 or SNN11

• Since primary alky halides are Since primary alky halides are notnot sterically sterically hindered; substitution likelyhindered; substitution likely

• Bulky Base favors elimination over Bulky Base favors elimination over substitutionsubstitution

Decreased crowding at carbon that bears the leaving Decreased crowding at carbon that bears the leaving group group increases substitution increases substitution relative to elimination. relative to elimination.

primary alkyl halideprimary alkyl halide

CHCH33CHCH22CHCH22BrBr

NaNaOOCHCH22CHCH33

ethanol, 55°Cethanol, 55°C

CHCH33CH=CHCH=CH22++CHCH33CHCH22CHCH22OOCHCH22CHCH33

(9%)(9%)(91%)(91%)

Uncrowded Alkyl HalidesUncrowded Alkyl Halides

primary alkyl halide + bulky baseprimary alkyl halide + bulky base

CHCH33(CH(CH22))1515CHCH22CHCH22BrBr

KKOOC(CHC(CH33))33

tert-tert-butyl alcohol, 40°Cbutyl alcohol, 40°C

++CHCH33(CH(CH22))1515CHCH22CHCH22OOC(CHC(CH33))33 CHCH33(CH(CH22))1515CH=CHCH=CH22

(87%)(87%)(13%)(13%)

But a crowded alkoxide base can favor elimination But a crowded alkoxide base can favor elimination even with a primary alkyl halide.even with a primary alkyl halide.

Substitution vs. Elimination Substitution vs. Elimination Effect of Alkyl HalideEffect of Alkyl Halide

3° RX3° RX

• SSNN2 is unlikely due to steric hinderance2 is unlikely due to steric hinderance

• Weak Nucleophile/ Polar Protic Solvent -> Weak Nucleophile/ Polar Protic Solvent -> E1/SE1/SNN11

– Steric hinderance of 3° RX make Steric hinderance of 3° RX make substitution unlikely except in solvolysis substitution unlikely except in solvolysis reactionsreactions

• Strong Base/ Bulky Base -> E2Strong Base/ Bulky Base -> E2

(CH(CH33))22CCHCCH22CHCH33

BrBr

++CHCH33CCHCCH22CHCH33

OOCHCH22CHCH33

CHCH33

CHCH22=CCH=CCH22CHCH33

CHCH33

CHCH33C=CHCHC=CHCH33

CHCH33

++

ethanol, 25°Cethanol, 25°C

64%64% 36%36%

22MM sodium ethoxide in ethanol, 25°C sodium ethoxide in ethanol, 25°C

1%1% 99%99%

ExampleExample

Substitution vs. Elimination Substitution vs. Elimination Effect of Alkyl HalideEffect of Alkyl Halide

2° RX2° RX

All mechanisms are possibleAll mechanisms are possible

• Strong Nucleophile but Weak Base -> SStrong Nucleophile but Weak Base -> SNN22

• Weak Nucleophile/Weak Base -> SWeak Nucleophile/Weak Base -> SNN1/E11/E1

• Strong Base/ Bulky Base -> E2Strong Base/ Bulky Base -> E2

Elimination vs. SubstitutionElimination vs. SubstitutionNucleophilicity vs. BasicityNucleophilicity vs. Basicity

Strong NucleophilesStrong Nucleophiles SSNN22

Strong BasesStrong Bases E2E2

Weak Nucleophiles/ Weak Weak Nucleophiles/ Weak BaseBase

E1 or SE1 or SNN11

Sterically Hindered Base or Sterically Hindered Base or NucleophileNucleophile

Elimination over Elimination over SubstitutionSubstitution

Substitution vs. EliminationSubstitution vs. Elimination

• Protic Polar -> E1, SProtic Polar -> E1, SNN11

• Aprotic Polar -> E2 / SAprotic Polar -> E2 / SNN22

• High Concentration -> SHigh Concentration -> SNN2/ E22/ E2

• Low Concentration -> SLow Concentration -> SNN1/E11/E1

Solvent EffectSolvent Effect

Effect of Nucleophile/Base ConcentrationEffect of Nucleophile/Base Concentration