Alkyl Halides

R-X (X = F, Cl, Br, I)

Classification of alkyl halides according to the class of the

carbon that the halogen is attached to.

RCH2-X R2CH-X R3C-X

1o 2o 3o
Nomenclature:
common names: “alkyl halide”
(fluoride, chloride, bromide, iodide)

IUPAC names: use rules for alkanes

halogen = halo (fluoro, chloro, bromo, iodo)
Cl
CH3CH2CH2CH2-Br CH3CHCH3
n-butyl bromide isopropyl chloride
1-bromobutane 2-chloropropane
1o 2o
 CH3 CH3
CH3CHCH2CHCH3 CH3CCH3
Br I
2-bromo-4-methylpentane tert-butyl iodide
2-iodo-2-methylpropane
2o 3o

CH3
Cl-CHCH2CH3

sec-butyl chloride
2-chlorobutane
2o
Physical properties:
polar + no hydrogen bonding
=> moderate boiling/melting points
water insoluble

Uses: pesticides, refrigerants (freons), solvents, synthetic

intermediates.

CH3Br CClF3 CCl4

Synthesis of alkyl halides:
1. From alcohols
a) HX b) PX3
2. Halogenation of certain hydrocarbons

3. (later)

4. (later)

5. Halide exchange for iodide

1. From alcohols. #1 synthesis!

a) With HX
R-OH + HX  R-X + H2O

i) HX = HCl, HBr, HI
ii) may be acid catalyzed (H+)
iii) ROH: 3o > 2o > CH3 > 1o
iv) rearrangements are possible except with most 1o ROH
CH3CH2CH2CH2-OH + NaBr, H2SO4, heat  CH3CH2CH2CH2-Br
n-butyl alcohol (HBr) n-butyl bromide
1-butanol 1-bromobutane

CH3 CH3
CH3CCH3 + HCl  CH3CCH3
OH Cl
tert-butyl alcohol tert-butyl chloride
2-methyl-2-propanol 2-chloro-2-methylpropane

CH3-OH + HI, H+,heat  CH3-I

methyl alcohol methyl iodide
methanol iodomethane
…from alcohols: b) PX3
i) PX3 = PCl3, PBr3, P + I2
ii) ROH: CH3 > 1o > 2o
iii) no rearragements

CH3CH2-OH + P, I2  CH3CH2-I
ethyl alcohol ethyl iodide
ethanol iodoethane

CH3 CH3
CH3CHCH2-OH + PBr3  CH3CHCH2-Br
isobutyl alcohol isobutyl bromide
2-methyl-1-propanol 1-bromo-2-methylpropane
2. Halogenation of certain hydrocarbons.
R-H + X2, Δ or hν  R-X + HX
(requires Δ or hν; Cl2 > Br2 (I2 NR); 3o>2o>1o)
yields mixtures!  In syntheses, limited to those
hydrocarbons that yield only one monohalogenated
product.

CH3 CH3
CH3CCH3 + Cl2, heat  CH3CCH2-Cl
CH3 CH3

neopentane neopentyl chloride

2,2-dimethylpropane 1-chloro-2,2-dimethylpropane
5. Halide exchange for iodide.
R-X + NaI, acetone  R-I + NaX 

i) R-X = R-Cl or R-Br

ii) NaI is soluble in acetone, NaCl/NaBr are insoluble.

CH3CH2CH2-Br + NaI, acetone  CH3CH2CH2-I

n-propyl bromide n-propyl idodide
1-bromopropane 1-idodopropane
 ROH

HX PX3

NaI
RX
acetone

X2, Δ or hν

RH
Outline a possible laboratory synthesis for each of the
following alkyl halides using a different synthesis for each
compound:

1-bromobutane neopentyl chloride

n-propyl iodide tert-butyl bromide

CH3CH2CH2CH2-OH + PBr3  CH3CH2CH2CH2-Br

CH3 CH3
CH3CCH3 + Cl2, heat  CH3CCH2-Cl
CH3 CH3

CH3CH2CH2-Br + NaI, acetone  CH3CH2CH2-I

CH3 CH3
CH3C-OH + HBr  CH3C-Br
CH3 CH3
 R-H R-X

Acids NR NR
Bases NR 
Active Metals NR 
Oxidants NR NR
Reductants NR 
Halogens NR NR
Reactions of alkyl halides:
1. Nucleophilic substitution Best with 1o or CH3!!!!!!
R-X + :Z-  R-Z + :X-
2. (later)
3. Preparation of Grignard Reagent
R-X + Mg  RMgX
4. Reduction
R-X + Mg  RMgX + H2O  R-H
R-X + Sn, HCl  R-H
 nucleophilic substitution

R-W + :Z-  R-Z + :W-

substrate nucleophile substitution leaving
product group

good nucleophile  strong base

good leaving group  weak base
R-X + :OH-  ROH + :X- alcohol
R-X + H2O  ROH + HX alcohol
R-X + :OR´-  R-O-R´ + :X- ether
R-X + -:CCR´  R-CCR´ + :X- alkyne
R-X + :I-  R-I + :X- iodide
R-X + :CN-  R-CN + :X- nitrile
R-X + :NH3  R-NH2 + HX primary amine
R-X + :NH2R´  R-NHR´ + HX secondary amine
R-X + :SH-  R-SH + :X- thiol
R-X + :SR´  R-SR´ + :X- thioether
Etc.
Best when R-X is CH3 or 1o!
CH3CH2CH2-Br + KOH  CH3CH2CH2-OH + KBr

CH3CH2CH2-Br + HOH  CH3CH2CH2-OH + HBr

CH3CH2CH2-Br + NaCN  CH3CH2CH2-CN + NaBr

CH3CH2CH2-Br + NaOCH3  CH3CH2CH2-OCH3 + NaBr

CH3CH2CH2-Br + NH3  CH3CH2CH2-NH2 + HBr

CH3CH2CH2-Br + NaI, acetone  CH3CH2CH2-I + NaBr

Mechanism for nucleophilic substitution:
“substitution, nucleophilic, bimolecular”

SN2
RDS
Z: + C W Z C + :W

“curved arrow formalism” uses arrows to show the movement

of pairs of electrons in a mechanism.
Kinetics – study of the effect of changes in concentration on
rates of reactions.

CH3—Br + NaOH  CH3—OH + NaBr

rate = k [ CH3-Br ] [ OH- ]

Tells us that both CH3-Br and OH- are involved in the rate
determining step of the mechanism. “bimolecular”
Relative rates of R—X

R-I > R-Br > R-Cl

“element effect”  C—X bond is broken in the rate

determining step of the mechanism.
SN2 stereochemistry
CH3 CH3

H Br + NaOH  HO H
(SN2 conditions)
C6H13 C6H13

(S)-(-)-2-bromooctane (R)-(+)-2-octanol
100% optical purity

SN2 proceeds with 100% inversion of configuration! (“backside attack”

by the nucleophile)
SN2 100% backside attack by the nucleophile
Evidence: stereochemistry = 100% inversion of
configuration

Reasonable?
1) incoming nucleophile and negatively charged leaving
group are as far apart as they can get.
2) there is more room on the backside of the carbon for the
incoming nucleophile to begin to bond to the carbon.
 Relative rates for alkyl halides in SN2:
CH3-X > 1o > 2o > 3o
37 : 1.0 : 0.2 : 0.0008

Z C W
 
Z: + C W Z C + :W

The transition state has five groups crowded around the carbon. If the
substrate is CH3X then three of the the five groups are Hydrogens. If the
alkyl halide is 3o then there are three bulky alkyl groups crowded around
the carbon in the transition state. “Steric factors” explain the relative
reactivity of alkyl halides in the SN2 mechanism.
 CH3 CH3
CH3CCH3 + OH-  CH3CCH3 + Br- + alkene
Br OH

rate = k [ tert-butyl bromide ]

The rate of this reaction depends on only the concentration of

the alkyl halide. Therefore the nucleophile is not involved in
the RDS here, cannot be SN2 mechanism!? “unimolecular”
Substitution, nucleophilic, unimolecular (SN1) mechanism:

RDS
1) C W C + :W

carbocation

2) + :Z C Z
C

Kinetics: rate = k [R-W ]; only R-W is involved in the RDS!

SN1 stereochemistry
CH3 CH3 CH3

H Br + NaOH  HO H + H OH
(SN1 conditions)
C6H13 C6H13 C6H13

(-)-2-bromooctane (+)-2-octanol (-)-2-octanol

SN1 proceeds with partial racemization. The intermediate carbocation is

sp2 hybridized. The nucleophile can attack the carbocation from either the
top or the bottom and yield both enantiomeric products.
SN1 reactivity: 3o > 2o > 1o > CH3

R—Br  R+ + Br-

CH3—Br ΔH = 219 Kcal/mole CH3+

CH3CH2—Br ΔH = 184 Kcal/mole 1o
CH3CH—Br ΔH = 164 Kcal/mole 2o
CH3

CH3
CH3C—Br ΔH = 149 Kcal/mole 3o
CH3
SN1 order of reactivity = 3o > 2o > 1o > CH3

Stability of carbocations = 3o > 2o > 1o > CH3+

RDS in SN1: R—W  R+ + :W-

R—X [ R---------X ]  R+ + X-
δ+ δ-
Rearrangement of carbocations.
Carbocations can rearrange by 1,2-hydride or 1,2-methyl shifts:

  [1,2-H]  
--C—C--  --C—C–
+   +
H H


  [1,2-CH3]  
--C—C--  --C—C–
+   +
CH3 CH3
Carbocations can rearrange by 1,2-hydride or 1,2-methyl shifts
but only do so when the resultant carbocation is more stable.
1o carbocation will rearrange to 2o
1o carbocation will rearrange to 3o
2o carbocation will rearrange to 3o
(only goes “down hill”)
 CH3 CH3
CH3CHCHCH3 + NaCN (SN1 conditions)  CH3CCH2CH3 ?????
Br CN

 
CH3 [ 1,2-H shift ] CH3
CH3CHCHCH3  CH3CCH2CH3 + CN-
+ +
2o carbocation 3o carbocation
Competing mechanisms for nucleophilic substitution

SN2
RDS
Z: + C W Z C + :W

SN1
RDS
C W C + :W

C + :Z C Z
 SN2 SN1

stereochemistry 100% inversion Partial racemization

Kinetic order Rate = k[RX][Z-] Rate = k[RX]

Rearrangements None Possible

Rates CH3,1o,2o,3o CH3>1o>2o>3o 3o>2o>1o>CH3

Rates RCl,RBr,RI RI>RBr>RCl RI>RBr>RCl

Rate? temp. Increases rate Increases rate

Rate? 2 x [RX] Doubles rate Doubles rate

Rate? 2 x [Z-] Doubles rate No effect

R-X + Z-  R-Z + X- which mechanism?

 SN2 -

CH3 1o 2o 3o
- SN1 

SN2 “steric factors” CH3 > 1o > 2o > 3o

SN1 carbocation stability 3o > 2o > 1o > CH3

Effect of solvent polarity on SN1/SN2:
water = polar ethanol = less polar
Solvent: mixture of ethanol/water
Add more water = more polar; add more ethanol = less polar.

SN1: R-W  R+ + W-
ionization favored by polar solvents

SN2: Z:- + R-W  Z-R + :X-

solvent polarity does not affect rate
Alkyl halide + base  ????

SN2: best with CH3 or 1o RX, concentrated, strong base

(SN1: 2o or 3o, dilute, weak base, polar solvent;

rearrangements are possible , alkene by-products )
Synthesis of alkyl halides:
1. From alcohols
a) HX b) PX3
2. Halogenation of certain hydrocarbons

3. (later)

4. (later)

5. Halide exchange for iodide

Reactions of alkyl halides:
1. Nucleophilic substitution Best with 1o or CH3!!!!!!
R-X + :Z-  R-Z + :X-
2. (later)
3. Preparation of Grignard Reagent
R-X + Mg  RMgX
4. Reduction
R-X + Mg  RMgX + H2O  R-H
R-X + Sn, HCl  R-H
Mechanisms

SN2
RDS
Z: + C W Z C + :W

SN1
RDS
C W C + :W

C + :Z C Z