2014.11.13 alkyl halides

32
04/12/2014 1 Alkyl Halides: Nucleophilic Organic Chemistry Substitution and Elimination Lecture November 13, 2014 Dr. Edi Munawar Edi Munawar Jurusan Teknik Kimia - Fakultas Teknik Universitas Syiah Kuala contact: [email protected] Classes of Halides Alkyl halides: Halogen, C H H C H Br X, is directly bonded to sp 3 carbon. Vinyl halides: X is bonded to sp 2 carbon of alkene. C C H H H Cl vinyl halide C H H C H Br alkyl halide Edi Munawar 2 Aryl halides: X is bonded to sp 2 carbon on benzene ring. vinyl halide I aryl halide

Upload: syarifah-humaira-almudhir

Post on 03-Dec-2015

267 views

Category:

Documents


1 download

DESCRIPTION

m

TRANSCRIPT

04/12/2014

1

Alkyl Halides: Nucleophilic

Organic Chemistry

y pSubstitution and Elimination

Lecture November 13, 2014

Dr. Edi Munawar

Edi Munawar

Jurusan Teknik Kimia - Fakultas TeknikUniversitas Syiah Kuala

contact: [email protected]

Classes of Halides

• Alkyl halides: Halogen, C

H

H C

H

Bry gX, is directly bonded to sp3 carbon.

• Vinyl halides: X is bonded to sp2 carbon of alkene.

C CH

H

H

Cl

vinyl halide

CH

H

C

H

Br

alkyl halide

Edi Munawar 2

• Aryl halides: X is bonded to sp2 carbon on benzene ring.

vinyl halideI

aryl halide

04/12/2014

2

Polarity and Reactivity

• Halogens are more electronegative than C.

Edi Munawar

• Carbon—halogen bond is polar, so carbon has partial positive charge.

• Carbon can be attacked by a nucleophile.

• Halogen can leave with the electron pair. 3

IUPAC Nomenclature

• Name as haloalkaneName as haloalkane.

• Choose the longest carbon chain, even if the halogen is not bonded to any of those C’s.

• Use lowest possible numbers for position.

CH CH CH CHCH CH CH

CH2CH2F1 2

CH CHCH CH

Cl

Edi Munawar 4

CH3CH2CH2CHCH2CH2CH331 2 4

2-chlorobutane 4-(2-fluoroethyl)heptane

1CH3CHCH2CH3

2 3 4 5 6 7

04/12/2014

3

Examples

BrCH3

CH3CHCH2CH2CH2CHCH2CH2CH3

Br

H

1

6-bromo-2-methylnonane 1

3

2 3 4 5 6 7 8 9

Edi Munawar 5

F H3

cis-1-bromo-3-fluorocyclohexane

Systematic Common Names

• The alkyl groups is a substituent on halide.

• Useful only for small alkyl groups.

CH3CHCH2

CH3

Br CH3CH2CH

CH3

Br CH3C

CH3

Br

Edi Munawar 6

CH3

iso-butyl bromide sec-butyl bromide tert-butyl bromide

04/12/2014

4

Common Names of Halides

• CH2X2 called methylene halideCH2X2 called methylene halide.• CHX3 is a haloform.• CX4 is carbon tetrahalide.• Common halogenated solvents:

CH2Cl2 is methylene chlorideCHCl is chloroform

Edi Munawar 7

CHCl3 is chloroform CCl4 is carbon tetrachloride.

Alkyl Halides Classification

• Methyl halides: halide is attached to a methyl groupgroup.

• Primary alkyl halide: carbon to which halogen is bonded is attached to only one other carbon.

• Secondary alkyl halide : carbon to which halogen is bonded is attached to two other carbons.

• Tertiary alkyl halide : carbon to which

Edi Munawar 8

Tertiary alkyl halide : carbon to which halogen is bonded is attached to three other carbon.

04/12/2014

5

Primary, Secondary, Tertiary Alkyl Halides

CH3 CH3

primary alkyl halide secondary alkyl halide

CH3CHCH2

CH3

Br CH3CH2CH

CH3

Br

CH3C

CH3

Br*

**

Edi Munawar 9

tertiary alkyl halide

CH3C Br

CH3

Types of Dihalides

• Geminal dihalide: Brtwo halogen atoms are bonded to the same carbon.

• Vicinal dihalide: two halogen atoms

b d d t

CH3 CH Br

CH2CH2Br Br

geminal dihalide

Edi Munawar 10

are bonded to adjacent carbons.

2 2

vicinal dihalide

04/12/2014

6

Uses of Alkyl Halides

• Industrial and household cleaners.• Anesthetics:

CHCl d i i ll l th ti b t it• CHCl3 used originally as general anesthetic but it is toxic and carcinogenic.

• CF3CHClBr is a mixed halide sold as Halothane® • Freons are used as refrigerants and foaming agents.

• Freons can harm the ozone layer so they have been replaced by low-boiling hydrocarbons or carbon dioxide.

P i id h DDT l i

Edi Munawar 11

• Pesticides such as DDT are extremely toxic to insects but not as toxic to mammals. • Haloalkanes can not be destroyed by bacteria so

they accumulate in the soil to a level which can be toxic to mammals, especially, humans.

Dipole Moments

• Electronegativities of the halides:F > Cl > B > IF > Cl > Br > I

• Bond lengths increase as the size of the halogen increases:

C—F < C—Cl < C—Br < C—I• Bond dipoles:

C—Cl > C—F > C—Br > C—I1.56 D 1.51 D 1.48 D 1.29 D

Edi Munawar 12

1.56 D 1.51 D 1.48 D 1.29 D

• Molecular dipoles depend on the geometry of the molecule.

04/12/2014

7

Boiling Points

• Greater intermolecular forces, higher b.p.• dipole-dipole attractions not significantly different

for different halides

• London forces greater for larger atoms

• Greater mass, higher b.p.

• Spherical shape decreases b.p.

Edi Munawar 13

(CH3)3CBr CH3(CH2)3Br

73C 102C

Densities

• Alkyl fluorides and chlorides less dense• Alkyl fluorides and chlorides less dense than water.

• Alkyl dichlorides, bromides, and iodides more dense than water.

Edi Munawar 14

04/12/2014

8

Preparation of Alkyl Halides

• Free radical halogenation (Chapter 4)• Chlorination produces a mixtures of

products. This reaction is not a good lab synthesis, except in alkanes where all hydrogens are equivalent.

• Bromination is highly selective.

Edi Munawar 15

• Free radical allylic halogenation• Halogen is placed on a carbon directly

attached to the double bond (allylic).

Halogenation of Alkanes

• Bromination is highly selective:

Edi Munawar 16

3º carbons > 2º carbons > 1º carbons

04/12/2014

9

Allylic Halogenation

• Allylic radical is resonance stabilized.

Edi Munawar 17

Allylic radical is resonance stabilized.

• Bromination occurs with good yield at the allylic position (sp3 C next to C C).

N-bromosuccinimide

• N-bromosuccinimide (NBS) is an allylic

Edi Munawar 18

brominating agent.

• Keeps the concentration of Br2 low.

04/12/2014

10

Reaction Mechanism

• The mechanism involves an allylic radical stabilized by resonance

Edi Munawar 19

stabilized by resonance.

• Both allylic radicals can react with bromine.

Substitution Reactions

• The halogen atom on the alkyl halide is replaced with a nucleophile (Nuc-)

Edi Munawar 20

a nucleophile (Nuc ).• Since the halogen is more electronegative than

carbon, the C—X bond breaks heterolytically and X-

leaves.

04/12/2014

11

Elimination Reactions

• Elimination reactions produce double bonds.

Edi Munawar 21

• The alkyl halides loses a hydrogen and the halide.

• Also called dehydrohalogenation (-HX).

SN2 Mechanism

• Bimolecular nucleophilic substitution.

Edi Munawar 22

• Concerted reaction: new bond forming and old bond breaking at same time.• Rate is first order in each reactant.• Walden inversion.

04/12/2014

12

SN2 Energy Diagram

Edi Munawar

• The SN2 reaction is a one-step reaction.

• Transition state is highest in energy. 23

Uses for SN2 Reactions

Edi Munawar 24

04/12/2014

13

SN2: Nucleophilic Strength

• Stronger nucleophiles react faster.• Strong bases are strong nucleophiles, but not

all strong nucleophiles are basic.

Edi Munawar 25

Basicity versus Nucleophilicity

B i it i d fi d b th ilib i t t

Edi Munawar

• Basicity is defined by the equilibrium constant for abstracting a proton.

• Nucleophilicity is defined by the rate of attack on the electrophilic carbon atom

26

04/12/2014

14

Trends in Nucleophilicity

• A negatively charged nucleophile is stronger th it t l t tthan its neutral counterpart:

OH- > H2O HS-> H2S NH2- > NH3

• Nucleophilicity decreases from left to right : OH- > F- NH3 > H2O

Edi Munawar 27

• Increases down Periodic Table, as size and polarizability increase:

I- > Br- > Cl-

Polarizability Effect

Edi Munawar

Bigger atoms have a soft shell which can start to overlap the carbon atom from a farther distance.

28

04/12/2014

15

Solvent Effects: ProticSolvents

Edi Munawar

• Polar protic solvents have acidic hydrogens (O—H or N—H) which can solvate the nucleophile reducing their nucleophilicity.

• Nucleophilicity in protic solvents increases as the size of the atom increases.

29

Solvent Effects: AproticSolvents

• Polar aprotic solvents do not have acidic protons and

Edi Munawar

• Polar aprotic solvents do not have acidic protons and therefore cannot hydrogen bond.

• Some aprotic solvents are acetonitrile, DMF, acetone, and DMSO.

30

04/12/2014

16

Crown Ethers

• Crown ethers solvate the cation, so the nucleophilicstrength of the anion increases.

• Fluoride becomes a d l hil

Edi Munawar 31

good nucleophile.

Leaving Group AbilityThe best leaving groups are:• Electron-withdrawing, to polarize the carbon atom.• Stable (not a strong base) once it has left.• Polarizable, to stabilize the transition state.

Edi Munawar 32

04/12/2014

17

Structure of Substrate on SN2 Reactions

• Relative rates for SN2: N

CH3X > 1° > 2° >> 3°

• Tertiary halides do not react via the SN2 mechanism, due to steric hindrance.

Edi Munawar 33

Steric Effects of the Substrate on SN2 Reactions

• Nucleophile approaches from the back side.

• It must overlap the back lobe of the C—X sp3

orbital.

Edi Munawar 34

04/12/2014

18

Stereochemistry of SN2

SN2 reactions will result in an inversion of configuration also called a Walden inversion.

Edi Munawar 35

The SN1 Reaction

• The SN1 reaction is a unimolecular N

nucleophilic substitution.

• It is a two step reaction with a carbocation intermediate.

• Rate is first order in the alkyl halide, d i th l hil

Edi Munawar 36

zero order in the nucleophile.

• Racemization occurs.

04/12/2014

19

SN1 Mechanism: Step 1

Edi Munawar

Formation of carbocation (rate determining step)

37

SN1 Mechanism: Step 2

• The nucleophile attacks the carbocation, f i th d t

Edi Munawar

forming the product.• If the nucleophile was neutral, a third step

(deprotonation) will be needed.

38

04/12/2014

20

SN1 Energy Diagram

• Forming the carbocation is an endothermic step.

• Step 2 is fast with a low activation energy

Edi Munawar

energy.

39

Rates of SN1 Reactions

• Order of reactivity follows stability of carbocations (opposite to SN2)• 3° > 2° > 1° >> CH3X

• More stable carbocation requires less energy to form.

• A better leaving group will increase the

Edi Munawar 40

• A better leaving group will increase the rate of the reaction.

04/12/2014

21

Solvation Effect

• Polar protic solvent best because it can solvate both ions strongly through hydrogen bonding.

Edi Munawar 41

Structure of the Carbocation

• Carbocations are sp2 hybridized and trigonal planar.

Edi Munawar

p y g pThe lobes of the empty p orbital are on both sides of the trigonal plane.

• Nucleophilic attack can occur from either side producing mixtures of retention and inversion of configuration if the carbon is chiral.

42

04/12/2014

22

Stereochemistry of SN1

Edi Munawar

The SN1 reaction produces mixtures of enantiomers.There is usually more inversion than retention ofconfiguration

43

Rearrangements

• Carbocations can rearrange to form a more stable carbocation.

• Hydride shift: H- on adjacent carbon bonds with C+.

• Methyl shift: CH3- moves from adjacent

b if h d il bl

Edi Munawar 44

carbon if no hydrogens are available.

04/12/2014

23

Hydride and Methyl Shifts

• Since a primary carbocation cannot form, the methyl

Edi Munawar

group on the adjacent carbon will move (along with both bonding electrons) to the primary carbon displacing the bromide and forming a tertiary carbocation.

• The smallest groups on the adjacent carbon will move: if there is a hydrogen it will give a hydride shift.45

SN1 or SN2 Mechanism?

SN2 SN1

CH3X > 1º > 2º 3º > 2º

Strong nucleophile Weak nucleophile (may also be solvent)

Polar aprotic solvent Polar protic solvent.

Rate = k[alkyl halide][Nuc] Rate = k[alkyl halide]

Edi Munawar

Rate k[alkyl halide][Nuc] Rate k[alkyl halide]

Inversion at chiral carbon Racemization

No rearrangements Rearranged products

46

04/12/2014

24

The E1 Reaction

• Unimolecular elimination.• Two groups lost: a hydrogen and the

halide.• Nucleophile acts as base.• The E1 and SN1 reactions have the

same conditions so a mixture of

Edi Munawar 47

same conditions so a mixture of products will be obtained.

E1 Mechanism

Step 1: halide ion leaves forming a carbocation

Edi Munawar

• Step 1: halide ion leaves, forming a carbocation.• Step 2: Base abstracts H+ from adjacent carbon

forming the double bond.

48

04/12/2014

25

A Closer Look

Edi Munawar 49

E1 Energy Diagram

Edi Munawar

• The E1 and the SN1 reactions have the same first step: carbocation formation is the rate determining step for both mechanisms.

50

04/12/2014

26

Double Bond Substitution Patterns

• The more substituted double bond is more stable.

tetrasubstituted trisubstituted disubstituted monosubstituted

Edi Munawar 51

• In elimination reactions, the major product of the reaction is the more substituted double bond: Zaitsev’s Rule.

Zaitsev’s Rule

• If more than one elimination product is possible, the most-substituted alkene is the major product (most stable).

Edi Munawar 52

major product(trisubstituted)

04/12/2014

27

The E2 Reaction

• Elimination, bimolecular

• Requires a strong base

• This is a concerted reaction: the proton is abstracted, the double bond forms and the leaving group leaves, all in one t

Edi Munawar 53

step.

The E2 Mechanism

Edi Munawar

• Order of reactivity for alkyl halides: 3° > 2 ° > 1°

• Mixture may form, but Zaitsev productpredominates.

54

04/12/2014

28

E2 Stereochemistry

• The halide and the proton to be abstracted must be anti-coplanar (=180º) to each other for the elimination to occur.

• The orbitals of the hydrogen atom and the halide must be aligned so they can begin to form a pi bond in the transition state.

Edi Munawar 55

• The anti-coplanar arrangement minimizes any steric hindrance between the base and the leaving group.

E2 Stereochemistry

Edi Munawar 56

04/12/2014

29

E1 or E2 Mechanism?

• Tertiary > Secondary • Tertiary > Secondary

• Base strength unimportant (usually weak)

• Good ionizing solvent

• Rate = k[alkyl halide]

• Zaitsev product

• Strong base required

• Solvent polarity not important.

• Rate =k[alkylhalide][base]

• Zaitsev product

Edi Munawar

Zaitsev product

• No required geometry

• Rearranged products

p

• Coplanar leaving groups (usually anti)

• No rearrangements

57

Substitution or Elimination?

• Strength of the nucleophile determines order: Strong nucleophiles or bases promote bimolecular reactions.

• Primary halide usually undergo SN2.

• Tertiary halide mixture of SN1, E1 or E2. Th t d S 2

Edi Munawar 58

They cannot undergo SN2.

• High temperature favors elimination.

• Bulky bases favor elimination.

04/12/2014

30

Secondary Alkyl Halides

• Secondary alkyl halides are more challenging:• Strong nucleophiles will promote S 2/E2• Strong nucleophiles will promote SN2/E2• Weak nucleophiles promote SN1/E1

• Strong nucleophiles with limited basicity favor SN2. Bromide and iodide are good examples of these.

Edi Munawar 59

Problem 1

Predict the mechanisms and products of the following reaction:

Edi Munawar

04/12/2014

31

Solution Problem 1

There is no strong base or nucleophile present, so thisti t b fi t d ith i i ti f threaction must be first order, with an ionization of the

alkyl halide as the slow step. Deprotonation of thecarbocation gives either of two elimination products,and nucleophilic attack gives a substitution product.

Edi Munawar 61

Problem 2

Predict the mechanisms and products of the following reaction:

Edi Munawar

04/12/2014

32

Solution Problem 2

This reaction takes place with a strong base, so it isd d Thi d h lid d b thsecond order. This secondary halide can undergo both

SN2 substitution and E2 elimination. Both products willbe formed, with the relative proportions of substitutionand elimination depending on the reaction conditions.

Edi Munawar