REAKSI ALKIL HALIDA: SUBSTITUSI DAN ELIMINASI NUKLEOFILIK

Nukleofil dan gugus pergi:

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

dapat menghasilkan produk eliminasi.

Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

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

Nukleofil netral menjadi bermuatan positif Nukleofil bermuatan negatif menjadi netral

Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

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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. Anion biasanya lebih reaktif dari yang netral.

Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

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Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

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Gugus Pergi A good leaving group reduces the barrier to a reaction Stable anions that are weak bases are usually excellent

leaving groups and can delocalize charge

Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

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“Super” Leaving Groups

Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

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Poor Leaving Groups

If a group is very basic or very small, it is prevents reaction

Reaction Kinetics The study of rates of reactions is called kinetics The order of a reaction is sum of the exponents

of the concentrations in the rate law – the first example is first order, the second one second order.

NaOH + C

CH3

CH3

CH3 Br NaBr + C

CH3

CH3

CH3 OH

v = k[C4H9Br]

NaOH + NaBr +

v = k[CH3Br][NaOH]

CH3Br CH3OH

The SN1 and SN2 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

characteristic step (bimolecular)

Stereochemical Modes of Substitution

Substitution with inversion:

Substitution with retention:

Substitution with racemization: 50% - 50%

SN2 Process

The reaction involves a transition state in which both reactants are together

“Walden” Inversion

Keadaan Transisi SN2 Keadaan transisi reaksi SN2 adalah planar,

karbon mengikat tiga gugus.

Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

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Urutan Kereaktifan Reaksi SN2

Semakin banyak gugus alkil terikat reaksi semakin lambat

Pengaruh sterik pada Reaksi SN2

The carbon atom in (a) bromomethane is readily accessibleresulting in a fast SN2 reaction. The carbon atoms in (b) bromoethane (primary), (c) 2-bromopropane (secondary), and (d) 2-bromo-2-methylpropane (tertiary) are successively more hindered, resulting in successively slower SN2 reactions.

Steric Hindrance Raises Transition State Energy

Steric effects destabilize transition states Severe steric effects can also destabilize

ground state

Very hindered

11.5 Characteristics of the SN2 Reaction

Sensitive to steric effects Methyl halides are most reactive Primary are next most reactive Secondary might react Tertiary are unreactive by this path No reaction at C=C (vinyl halides)

The SN1 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 SN1 reaction – occurs in two distinct steps while SN2 occurs with both events in same step

Stereochemistry of SN1 Reaction

The planar intermediate leads to loss of chirality A free

carbocation is achiral

Product is racemic or has some inversion

SN1dalam Kenyataannya Karbokation cenderung bereaksi pada sisi

yang berlawanan dari gugus pergi lepas Suggests reaction occurs with carbocation

loosely associated with leaving group during nucleophilic addition

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 ion pair

SN1 Energy Diagram

Rate-determining step is formation of carbocation

Step through highest energy point is rate-limiting (k1 in forward direction)

k1 k2k-1

V = k[RX]

11.9 Characteristics of the SN1 Reaction Tertiary alkyl halide is most reactive

by this mechanismControlled by stability of carbocation

Delocalized Carbocations

Delocalization of cationic charge enhances stability

Primary allyl is more stable than primary alkyl Primary benzyl is more stable than allyl

Perbandingan : Mekanisme Substitusi

SN1Dua tahap dengan hasil antara karbokationTerjadi pada 3°, allil, benzil

SN2Satu tahap tanpa hasil antaraTerjadi pada alkil halida primer dan sekunder

Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

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Effect of Leaving Group on SN1 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

p-Toluensulfonate (TosO-) is excellent leaving group

Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

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Allylic and Benzylic Halides

Allylic and benzylic intermediates stabilized by delocalization of charge (See Figure 11-13) Primary allylic and benzylic are also more

reactive in the SN2 mechanism

Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

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Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

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

slow SN2 reactions by associating with reactants Energy is required to break interactions between

reactant and solvent Polar aprotic solvents (no NH, OH, SH) form weaker

interactions with substrate and permit faster reaction

Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

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Polar Solvents Promote Ionization Polar, protic and unreactive Lewis base solvents

facilitate formation of R+ Solvent polarity is measured as dielectric

polarization (P)

Solvent Is Critical in SN1

Stabilizing carbocation also stabilizes associated transition state and controls rate

Solvation of a carbocation by water

Effects of Solvent on Energies

Polar solvent stabilizes transition state and intermediate more than reactant and product

Polar aprotic solvents Form dipoles that have well localized

negative sides, poorly defined positive sides.

Examples: DMSO, HMPA (shown here)

+

-

++

O

PN N NCH3

CH3CH3 CH3

CH3CH3

Common polar aprotic solventsCH3

S

O

CH3

O

PN N NCH3

CH3CH3 CH3

CH3CH3

CH

O

NCH3

CH3

SO O

dimethylsulfoxide (DMSO)

hexamethylphosphoramide (HMPA)

N,N-dimethylformamide (DMF)

sulfolane

+

-

+++

-

++

+-

++

+ -++

Na+

+

-

++

+

-

++

+-

++

+ -

++Cl-

Polar aprotic solvents solvate cations well, anions poorly

good fit! bad fit!

SN1: 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.

(slow)

SN2: Things get tight if highly solvated nucleophile tries to form pentacoordiante transition state

Polar aprotic solvents favored! There is no carbocation to be solvated.

Nucleophiles in SN1

Since nucleophilic addition occurs after formation of carbocation, reaction rate is not affected normally affected by nature or concentration of nucleophile

REAKSI ELIMINASI ALKIL HALIDA Eliminasi merupakan salah satu jalan alternatif

dari suatu reaksi substitusi Lawan dari reaksi adisi Menghasilkan alkena Menurunkan produk substitusi terutama SN1

Aturan Zaitsev’s untuk Reaksi Eliminasi (1875)

Pada eliminasi HX dari suatu alkil halida, produk tersubstitusi lebih dominan

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

departure of leaving group

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

Product alkene forms stereospecifically

Geometry of Elimination – E2

Antiperiplanar allows orbital overlap and minimizes steric interactions

E2 Stereochemistry

Overlap of the developing orbital in the transition state requires periplanar geometry, anti arrangement

Allows orbital overlap

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

(E)-1bromo-1,2-diphenylethene

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)

Equatorial groups are not in proper alignment

11.14 The E1 Reaction Competes with SN1 and E2 at 3° centers V = k [RX]

Stereochemistry of E1 Reactions E1 is not stereospecific and there is no

requirement for alignment Product has Zaitsev orientation because step

that controls product is loss of proton after formation of carbocation

Comparing E1 and E2

Strong base is needed for E2 but not for E1 E2 is stereospecifc, E1 is not E1 gives Zaitsev orientation

11.15 Summary of Reactivity: SN1, SN2, E1, E2

Alkyl halides undergo different reactions in competition, depending on the reacting molecule and the conditions

Based on patterns, we can predict likely outcomes

Special cases, both SN1 and SN2 blocked (or exceedingly slow)

Br

Br

Br

CH3

CH3CH3

CH2Br

Carbocation highly unstable, attack from behind blocked

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 blockedAlso: elimination not possible, can’t place double bond at bridgehead in small cages (“Bredt’s rule”)

Kinetic Isotope Effect Substitute deuterium for hydrogen at position Effect on rate is kinetic isotope effect (kH/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 rate-

limiting step