Unit 4

Nomenclature and Properties of Alkyl Halides

Synthesis of Alkyl Halides

Reactions of Alkyl Halides

Mechanisms of SN1, SN2, E1, and E2 Reactions

Substrate, Nucleophilicity, and Leaving Group Effects

Alkyl Halides

Alkyl halide: a compound with a halogen atom bonded to

one of the sp3 hybrid carbon atoms of an alkyl group

Two types of names: IUPAC system Common names

Nomenclature

IUPAC System: Alkyl halides are named as an alkane with a

halo-substituent: Review the rules for naming alkanes

covered in Unit 2

CH3CH2CH2Cl

BrCH3CH2CH2Cl

Br

1-chloropropane bromocyclohexane

Nomenclature

Common Names: alkyl group name + halide

CH3CH2CH2Cl

Br

CH3CH2CH2Cl

Br

n-propyl chloride Cyclohexyl bromide

Nomenclature

Special common names: CH2X2 = methylene halide CHX3 = haloform CX4 = carbon tetrahalide

CH2Cl2 CHCl3

CCl4

chloroformtrichloromethane

Methylene chloridedichloromethane

Carbon tetrachloridetetrachloromethane

Types of Alkyl Halides

Alkyl halides can be classified by the type of carbon atom the halogen is bonded to: primary halide (1o):

halogen attached to a 1o carbon

secondary halide (2o): halogen attached to a 2o carbon

tertiary halide (3o): halogen attached to a 3o carbon

CH3CH2CH2Cl

Br

CH3CH2CH2Cl

CH3CHBr

Br

CH3

CH3CH2CH2Cl

(CH3)3CBr

Br

Types of Alkyl Halides

Geminal dihalide: 2 halogens bonded to the same carbon

atom

Vicinal dihalide: 2 halogens bonded to adjacent carbon

atoms

CH3CH2CH2Cl

(CH3)3CBr

H

Br

C

Cl

Cl

H

CH3CH2CH2Cl

(CH3)3CBr

HCH3CHCH2

Cl

Br

C

Cl

Cl

H

ClCl

Cl

Other Organic Halides Aryl halide:

halogen is attached directly to an aromatic ring

Benzylic halide halogen is attached to a carbon that is

attached to a benzene ring

C

C

CF

F

F

F

CCl

H

H

H

HO

I

I

I

I

CH2

CH

NH2

CO2H

thyroxine

CH2Cl

benzylic carbon

benzylic chloride

C

C

CF

F

F

F

CH

H

H

HO

I

I

I

I

CH2

CH

NH2

CO2H

CH2Cl

Other Organic Halides

Allylic halide: halogen is attached to a carbon that is

attached to a C=C

Allylic carbon

Allylic chloride

Other Organic Halides

Vinyl Halide: halogen attached to a carbon that is part of

a C=C

C

C

CF

F

F

F

CCl

H

H

H

HO

I

I

I

I

CH2

CH

NH2

CO2H

C

C

CF

F

F

F

CCl

H

H

H

HO

I

I

I

I

CH2

CH

NH2

CO2H

Monomer for PVC Monomer for teflon

Uses of Alkyl Halides

Anesthetics: Chloroform (CHCl3)

toxic carcinogenic (causes cancer)

Solvents: CCl4

formerly used in dry cleaning CH2Cl2

formerly used to decaffeinate coffee liquid CO2 used now

Uses of Alkyl Halides

Freons: Freon-12: CF2Cl2

Freon-22: CHClF2

Freon-134a:

Pesticides:

Cl C

Cl

Cl

C

H

Cl

Cl

DDT

Cl C

Cl

Cl

C

H

Cl

Cl

Cl Cl

Cl

ClCl

Cl

Cl ClChlordane (termites)

C CF

F

F

F

H

H

Physical Properties

Boiling Point: Compounds with higher MW’s and greater

surface area (more linear) tend to have higher BP.

BP increases as size of halogen increases F < Cl < Br < I

BP decreases as branching increases

Physical Properties

Density: Alkyl chlorides are common solvents for

organic reactions.

CH2Cl2

CHCl3

CCl4

More dense than water

Preparation of Alkyl Halides

Alkyl halides can be prepared from a variety of starting materials including alkanes, alkenes, alkynes, alcohols, and other alkyl halides.

You are responsible for knowing and applying the synthesis of R-X by: free radical halogenation reactions free radical allylic bromination reactions

Preparation of Alkyl Halides

Free Radical Halogenation of Alkanes

alkane + X2 alkyl halide(s) + HX

Limited utility due to generally poor selectivity and yield. Useful when only one type of reactive hydrogen

is present

Bromination is more selective and gives the product formed from the most stable free radical.

hor

Preparation of Alkyl Halides

Useful Examples:

+ Cl2 + HCl

CH3 CH3+ Br2

Cl

C

CH3

CH3

H C

CH3

CH3

Br

h

h

50 %

90 %

+ Cl2 + HCl

CH3 CH3+ Br2+ HBr

Cl

C

CH3

CH3

H C

CH3

CH3

Br

Preparation of Alkyl Halides

Free Radical Allylic Bromination:

where NBS = N-bromosuccinimide

C + NBS CCC

H

CC

Br

h

+ HBr N

O

O

Br N

O

O

H + Br2

NBS

Preparation of Alkyl Halides

Allylic bromination more selective

allylic free radical is resonance stabilized

Addition of Br2 to the double bond is a competing reaction

use low levels of Br2 by generating it “in situ” using NBS

HH

H

HH

H

HH

H

HH

H

Preparation of Alkyl Halides

Examples:

+ NBS

Br

h

+ NBS

+ NBS

+ NBS

Br

Br

Br

h

Reactions of RX

Most reactions of alkyl halides involve breaking the C-X bond. Nucleophilic substitution Elimination

The halogen serves as a leaving group in these reactions: nucleophile can attack the carbon bearing

the +

the halogen can leave as X-, taking the bonding electrons with it

C X+ -

Reactions of RX

Nucleophilic substitution: reaction in which a nucleophile replaces a

leaving group

Nucleophile: electron pair donor

Leaving group: an atom or group of atoms that are lost during

a substitution or elimination reaction retains both electrons from the original bond

Reactions of RX

General Equation for Nucleophilic Substitution

Example:

C

C + X

+ CH3O

C

H

X + Nuc C Nuc

Br OCH3-+ Br-

-C C + X

CH2Cl

C X + Nuc C Nuc-

Reactions of RX

Elimination Reaction: two substituents are lost from adjacent

(usually) carbons, forming a new bond

Dehydrohalogenation: an elimination reaction in which H+ and X-

are lost, forming an alkene

C CC CH3

H

H

H CH3

Br

CH

H

CH3

CH3

C CC CH3

H

H

H CH3

Br

CH

H

CH3

CH3

CH3O-

Reactions of RX There are two common types of nucleophilic

substitution reactions: SN1 reactions

substitution, nucleophilic, unimolecular 3o, allylic, benzylic halides weak nucleophiles

SN2 reactions substitution, nucleophilic, bimolecular

methyl and 1o halides strong nucleophiles

Reactions of RX

Reactions of RX

Common strong nucleophiles: hydroxide ion alkoxide ions many amines iodide and bromide ions cyanide ion

Common weak nucleophiles: water alcohols fluoride ion

SN2 Reactions

The reaction between methyl iodide and hydroxide ion is a concerted reaction that takes places via an SN2 mechanism

HO + H HOC

H

H

I C

H

H

H + I- -

nucleophile

substrate product Leaving group

Substrate: the compound attacked by a reagent

(nucleophile)

SN2 Reactions

Concerted reaction: a reaction that takes place in a single step

with bonds breaking and forming simultaneously

SN2: substitution, nucleophilic, bimolecular transition state of rate-determining step

involves collision of 2 molecules 2nd order overall rate law

Rate = k[RX][Nuc]

SN2 Reactions

SN2 Mechanism: Nucleophile attacks the back side of the

electrophilic carbon, donating an e- pair to form a new bond

Since carbon can only have 8 valence electrons, the C-X bond begins to break as the C-Nuc bond begins to form

Nuc C Nuc C X

Nuc + X

H

HH X

H

HH

CH

HH

Nuc C Nuc C X

Nuc + X

H

HH X

H

HH

CH

HH

---

SN2 Reactions SN2 Mechanism for the reaction of methyl iodide and

hydroxide ion:

HO C

HO

HOI

H

HH

C I

HH

H

CH

HH

HO C

HO

HOI

H

HH

C I

HH

H

CH

HH

-

HO C HO

C HO C I

I

H

HH

H

CH

HH

HH

-

HO C

HO

HOI

H

HH

C I

HH

H

CH

HH

+ I -

SN2 Reactions

Reaction Energy Diagram: large Ea due to 5-coordinate carbon atom in

transition state no intermediates

exothermic

SN2 Reactions

SN2 reactions occur with inversion of configuration at the electrophilic carbon. The nucleophile attacks from the back side

(the side opposite the leaving group). Back-side attack turns the tetrahedron of

the carbon atom inside out.

SN2 Reactions

Inversion of configuration: a process in which the groups bonded to a

chiral carbon are changed to the opposite spatial configuration:

R S or S R

SN2 Reactions

Example: Predict the product formed by the SN2 reaction between (S)-2-bromobutane and hydroxide ion. Draw the mechanism for the reaction.

SN2 Reactions

The SN2 displacement reaction is a stereospecific reaction a reaction in which a specific stereoisomer

reacts to give a specific diastereomer of the product

H

CH3

Br

H

H

CH3

H

Br

H H

BrCH3

H

CH3

Br

H

H

CH3

H

Br

H

HCH3

OH+ OH-

Br

OH

H

CH3

Br

H

H

CH3

H

Br

HH

CH3

+ Br -

SN2 Reactions

SN2 reactions occur under the following conditions Nucleophile:

strong, unhindered nucleophile OH- not H2O CH3O- not CH3OH CH3CH2O- not (CH3)3CO-

Substrate: 1o or methyl alkyl halide (most favored) 2o alkyl halide (sometimes) 3o alkyl halides NEVER react via SN2

SN2 Reactions

The relative rate of reactivity of simple alkyl halides in SN2 reactions is:

methyl > 1o > 2o >>>3o

3o alkyl halides do not react at all via an SN2 mechanism due to steric hinderance. The back side of the electrophilic carbon

becomes increasingly hindered as the number or size of its substituents increases

SN2 Reactions

Steric hinderance at the electrophilic carbon:

SN2 Reactions

SN2 reactions can be used to convert alkyl halides to other functional groups: RX + I - R-I RX + OH- R-OH RX + R’O- R-OR’ RX + NH3 R-NH3

+ X-

RX + xs NH3 R-NH2

RX + CN- R-CN RX + HS- R-SH RX + R’S- R-SR’ RX + R’COO- R’CO2R

KNOW THESE!

Be able to apply these!

SN2 Reactions

Example: Predict the product of the following reactions:

(CH3)

2CHCH

2CH

2Cl + NH

3 (xs)

CH3CH

2CH

2CH

2Cl + NaCN

(CH3)

2CHCH

2CH

2Cl + NH

3 (xs)

CH3CH

2CH

2CH

2Cl + NaCN

SN2 Reactions

Example: What reagent would you use to do the following reactions:

(CH3)

2CHCH

2CH

2Cl + NH

3 (xs)

CH3CH

2CH

2CH

2Cl + NaCN

CH3CH2CH2Br + CH3CH2CH2OCH2CH3?

(CH3)

2CHCH

2CH

2Cl + NH

3 (xs)

CH3CH

2CH

2CH

2Cl + NaCN

CH3CH2CH2Br + CH3CH2CH2OCH2CH3

CH3CH2I + CH3CH2C CH?