REAKSI ALKIL HALIDA: SUBSTITUSI DAN ELIMINASI NUKLEOFILIK

(1)

REAKSI ALKIL HALIDA

:

(2)

(3)

Reaksi alkil halida dengan nukleofil

 Alkil halida terpolarisasi pada ikatan

karbon-halida, membuat karbon menjadi elektrofil.

 Nukleofil mengganti halida pada ikatan C-X

(sebagai basa Lewis)

 Nukleofil yang memeiliki basa Brønsted kuat

(4)

Based on McMurry, Organic Chemistry,

Nukleofil

 Basa Lewis yang netral atau bermuatan negatif  Perubahan muatan pada reaksi nukleofil

(5)

Reaktifitas Relatif Nukleofil

 Tergantung pada kondisi reaksi

 Nukleofil dengan sifat basa lebih kuat bereaksi lebih

cepat untuk struktur yang sama.

 Nukleofil yang baik terletak lebih bawah dalam SPU.

(6)

(7)

Gugus Pergi

 A good leaving group reduces the barrier to a reaction

 Stable anions that are weak bases are usually excellent

(8)

(9)

Poor Leaving Groups

 If a group is very basic or very small, it is

(10)

Reaction Kinetics

 The study of rates of reactions is called kinetics

 The order of a reaction is sum of the exponents

(11)

The S

_N

1 and S

_N

2 Reactions

 Follow first or second order reaction kinetics  Ingold nomenclature to describe characteristic

step:

 S=substitution

 _{N (subscript) = nucleophilic}

 1 = substrate in characteristic step (unimolecular)  _{2 = both nucleophile and substrate in}

(12)

Stereochemical Modes of

Substitution

 Substitution with inversion:

 Substitution with retention:

(13)

S

_N

2 Process

 The reaction involves a transition state in which

(14)

(15)

Keadaan Transisi S

_N

2

 Keadaan transisi reaksi S_N2 adalah planar,

(16)

Urutan Kereaktifan Reaksi S

_N

2

 Semakin banyak gugus alkil terikat reaksi

(17)

Pengaruh sterik pada Reaksi S

_N

2

The carbon atom in (a) bromomethane is readily accessible

resulting in a fast S_N2 reaction. The carbon atoms in (b) bromoethane

(18)

Steric Hindrance Raises

Transition State Energy

 Steric effects destabilize transition states  Severe steric effects can also destabilize

ground state

(19)

11.5 Characteristics of the S

_N

2 Reaction

 Sensitive to steric effects

 Methyl halides are most reactive  Primary are next most reactive  Secondary might react

(20)

The S

_N1

Reaction

 Tertiary alkyl halides react rapidly in protic

solvents by a mechanism that involves

departure of the leaving group prior to addition of the nucleophile

 Called an S

N1 reaction – occurs in two distinct

steps while S_N2 occurs with both events in same

(21)

Stereochemistry of S

_N

1 Reaction

carbocation is achiral

 Product is

(22)

S

_N

1dalam Kenyataannya



Karbokation cenderung bereaksi pada sisi

yang berlawanan dari gugus pergi lepas



Suggests reaction occurs with carbocation

(23)

Effects of Ion Pair Formation

 If leaving group remains

associated, then product has more

inversion than retention

 Product is only partially

racemic with more

inversion than retention

 Associated carbocation

and leaving group is an

(24)

S

_N

1 Energy Diagram

 Rate-determining step

is formation of carbocation

(25)

11.9 Characteristics of the S

_N

1 Reaction



Tertiary alkyl halide is most reactive

by this mechanism

(26)

Delocalized Carbocations

 Delocalization of cationic charge enhances

stability

(27)

Perbandingan : Mekanisme Substitusi



S

_N

1

Dua tahap dengan hasil antara karbokation Terjadi pada 3°, allil, benzil



S

_N

2

Satu tahap tanpa hasil antara

(28)

Effect of Leaving Group on S

_N

1

 Critically dependent on leaving group

 Reactivity: the larger halides ions are better leaving

groups

 In acid, OH of an alcohol is protonated and leaving group

is H₂O, which is still less reactive than halide

(29)

Allylic and Benzylic Halides

 Allylic and benzylic intermediates stabilized by

delocalization of charge (See Figure 11-13)

 _{Primary allylic and benzylic are also more}

(30)

(31)

The Solvent

 Solvents that can donate hydrogen bonds (-OH or –NH)

slow S_N2 reactions by associating with reactants

 Energy is required to break interactions between

reactant and solvent

 Polar aprotic solvents (no NH, OH, SH) form weaker

(32)

(33)

Polar Solvents Promote

Ionization

 Polar, protic and unreactive Lewis base solvents

facilitate formation of R+

 Solvent polarity is measured as dielectric

(34)

Solvent Is Critical in S

_N

1



Stabilizing carbocation also stabilizes

associated transition state and controls

rate

(35)

Effects of Solvent on Energies

 Polar solvent stabilizes transition state and

(36)

Polar aprotic solvents

 Form dipoles that have well localized

negative sides, poorly defined positive sides.

 Examples: DMSO, HMPA (shown here)

(37)

Common polar aprotic solvents

hexamethylphosphoramide (HMPA)

N,N-dimethylformamide (DMF)

(38)

+

Polar aprotic solvents solvate cations well, anions poorly

(39)

S

_N

1: Carbocation not very

encumbered, but needs to be

solvated in rate determining step

Polar protic solvents are good because they solvate both the leaving group and the carbocation in the rate determining step k₁!

The rate k₂ is somewhat reduced if the nucleophile is highly solvated, but this doesn’t matter since k₂ is inherently fast and not rate

determining.

(40)

S

_N

2: Things get tight if highly

solvated nucleophile tries to form

pentacoordiante transition state

(41)

Nucleophiles in S

_N

1



Since nucleophilic addition occurs

after

(42)

REAKSI ELIMINASI ALKIL HALIDA

 Eliminasi merupakan salah satu jalan alternatif

dari suatu reaksi substitusi

 Lawan dari reaksi adisi  Menghasilkan alkena

(43)

Aturan Zaitsev’s untuk Reaksi Eliminasi (1875)

 Pada eliminasi HX dari suatu alkil halida, produk

(44)

Mechanisms of Elimination

Reactions

 Ingold nomenclature: E – “elimination”

 E1: X- leaves first to generate a carbocation

 a base abstracts a proton from the carbocation

 E2: Concerted transfer of a proton to a base and

(45)

11.11 The E2 Reaction

Mechanism

 A proton is transferred to base as leaving

group begins to depart

 Transition state combines leaving of X and

transfer of H

(46)

Geometry of Elimination – E2

 Antiperiplanar allows orbital overlap and

(47)

E2 Stereochemistry

 Overlap of the developing _ orbital in the

transition state requires periplanar geometry, anti arrangement

(48)

(49)

Predicting Product

 E2 is stereospecific

 Meso-1,2-dibromo-1,2-diphenylethane with base

gives cis 1,2-diphenyl

 RR or SS 1,2-dibromo-1,2-diphenylethane gives

trans 1,2-diphenyl

(50)

(51)

11.12 Elimination From

Cyclohexanes

 Abstracted proton and leaving group should

align trans-diaxial to be anti periplanar (app) in approaching transition state (see Figures 11-19 and 11-20)

(52)

11.14 The E1 Reaction

(53)

Stereochemistry of E1

Reactions

 E1 is not stereospecific and there is no

requirement for alignment

 Product has Zaitsev orientation because step

(54)

Comparing E1 and E2

 Strong base is needed for E2 but not for E1  E2 is stereospecifc, E1 is not

(55)

11.15 Summary of Reactivity: S

_N

1 ,

S

_N

2 , E

₁

, E

₂

 Alkyl halides undergo different reactions in

competition, depending on the reacting molecule and the conditions

 Based on patterns, we can predict likely

(56)

(57)

(58)

Special cases, both S

_N

1 and S

_N

2 blocked (or exceedingly slow)

Br

Carbocation highly unstable, attack from behind blocked

Carbocation would be primary, attack from behind difficult due to steric blockage

Carbocation can’t flatten out as required by sp2

hybridization, attack from behind blocked

(59)

Kinetic Isotope Effect

 Substitute deuterium for hydrogen at _ position  _{Effect on rate is}_{kinetic isotope effect}_(k

H/kD =

deuterium isotope effect)

 Rate is reduced in E2 reaction

 _{Heavier isotope bond is slower to break}

 _{Shows C-H bond is broken in or before}

(60)

(61)

(62)

(63)