REAKSI ALKIL HALIDA: SUBSTITUSI DAN ELIMINASI NUKLEOFILIK
REAKSI ALKIL HALIDA:
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. Nukleofil
Basa Lewis yang netral atau bermuatan negatif
Perubahan muatan pada reaksi nukleofil
Nukleofil netral menjadi bermuatan positif
Nukleofil bermuatan negatif menjadi netral 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.
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
“Super” Leaving Groups 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.CH 3 CH 3 NaOH + CH C Br 3 NaBr + CH C OH 3 CH 3 CH 3 v = k[C H Br] 4 9 NaOH + CH Br NaBr + 3 CH OH 3 v = k[CH Br][NaOH] 3
1
N N
2 The S and S 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% S N
2 Process
The reaction involves a transition state in which both reactants are together
“Walden” Inversion Keadaan Transisi S N
2
Keadaan transisi reaksi S N 2 adalah planar, karbon mengikat tiga gugus. Urutan Kereaktifan Reaksi S N
2
Semakin banyak gugus alkil terikat reaksi semakin lambat Pengaruh sterik pada Reaksi S
2 N The carbon atom in (a) bromomethane is readily accessible resulting in a fast S 2 reaction. The carbon atoms in (b) bromoethane N
(primary), (c) 2-bromopropane (secondary), and (d) 2-bromo-2-methylpropane
(tertiary) are successively more hindered, resulting in successively slower S N
2 reactions. Steric Hindrance Raises Transition State Energy Very hindered
Steric effects destabilize transition states
Severe steric effects can also destabilize ground state
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
Tertiary are unreactive by this path
No reaction at C=C (vinyl halides)
N
1 The S 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
N
1 Called an S reaction – occurs in two distinct
2
steps while S occurs with both events in same N step
1 Stereochemistry of S Reaction N
The planar intermediate leads to loss of chirality
A free carbocation is achiral
Product is racemic or has some inversion
1dalam Kenyataannya S N
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 S N
1 Energy Diagram
Rate-determining step is formation of carbocation
Step through highest energy point is rate-limiting (k 1 in forward direction) k 1 k 2 k
- -1
V = k[RX]
1
11.9 Characteristics of the S
N Reaction
Tertiary alkyl halide is most reactive by this mechanism
Controlled 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
S N
1
Dua tahap dengan hasil antara karbokation
Terjadi pada 3°, allil, benzil
S N
2
Satu tahap tanpa hasil antara
Terjadi pada alkil halida primer dan sekunder Effect of Leaving Group on S
1 N
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 H O, which is still less reactive than halide 2
- -
p-Toluensulfonate (TosO ) is excellent leaving group 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 S N 2 mechanism
The Solvent
Solvents that can donate hydrogen bonds (-OH or –NH) slow S 2 reactions by associating with reactants N
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 reactionPolar Solvents Promote Ionization
Polar, protic and unreactive Lewis base solvents facilitate formation of R
- +
Solvent polarity is measured as dielectric
polarization (P)
1 Solvent Is Critical in S N
Stabilizing carbocation also stabilizes
associated transition state and controls
rateSolvation 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 - CH CH 3 P 3 CH CH 3 CH N N N CH 3 3
3
CH 3 3 O P CH CH 3 3 hexamethylphosphoramide (HMPA)
N N N CH CH 3 3 CH CH 3 3 O C CH 3 H N N,N-dimethylformamide (DMF) CH 3 sulfolane
S O O
Polar aprotic solvents solvate cations well, anions poorly
Na
- Cl
good fit! bad fit! S 1: Carbocation not very N encumbered, but needs to be solvated in rate determining step
(slow) Polar protic solvents are good because they solvate both the leaving group and the carbocation in the rate determining step k ! 1 The rate k is somewhat reduced if the nucleophile is highly solvated, 2 but this doesn’t matter since k is inherently fast and not rate 2 S 2: Things get tight if highly N
solvated nucleophile tries to form
pentacoordiante transition statePolar aprotic solvents favored! There is no carbocation to be solvated.
1 Nucleophiles in S N
Since nucleophilic addition occurs after
formation of carbocation, reaction rate is
not affected normally affected by nature or concentration of nucleophileREAKSI ELIMINASI ALKIL HALIDA
Eliminasi merupakan salah satu jalan alternatif dari suatu reaksi substitusi
Lawan dari reaksi adisi
Menghasilkan alkena
Menurunkan produk substitusi terutama S N
1 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 S N 1 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
1
11.15 Summary of Reactivity: S ,
N
N
1
2
2 S , E , E
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 S 1 and S
2 N N blocked (or exceedingly slow) Br Carbocation highly unstable, attack from behind blocked
2 Carbocation can’t flatten out as required by sp hybridization, attack from behind blocked Br Also: elimination not possible, can’t place double bond at bridgehead in small cages (“Bredt’s rule”) Br Carbocation highly unstable, attack from behind blocked
CH 3 CH Br CH 3 2 Carbocation would be primary, attack from behind difficult due to steric blockage Kinetic Isotope Effect
Substitute deuterium for hydrogen at position
Effect on rate is kinetic isotope effect (k H /k D = 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