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 reaction

  Polar 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

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 - CH CH 3 P 3 CH CH 3 CH N N N CH 3 3

3

Common polar aprotic solvents O S dimethylsulfoxide (DMSO) CH

  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 state

  Polar 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 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 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