Chapter 6

Halohydrocarbons
B. Nucleophilic Substitution reaction Mechanisms

(a) CH3Br + OH- CH3OH + Br-

υ= k[CH3Br][OH-] Second order

SN2 Nucleophilic Substitution Bimolecular

(b) (CH3)3CBr + OH-/H2O (CH3)3COH + Br-

υ= k[(CH3)3CBr] First order

SN1 Nucleophilic Substitution Unimolecular

Chapter 6 2
1. The SN2 Mechanism

H H H
-
H O C Br HO C Br HO C + Br
H H
H H H H

Five-centered transition state

• One-step process
• Concerted reaction: new bond forming
and old bond breaking at same time.

Chapter 6 3
 SN2 Energy Diagram

• Transition state is highest in energy.

Chapter 6 4
 Stereochemistry of SN2
Walden inversion

CH3 CH3 CH3

 
OH HO C Br + Br
H H
Br HO
H3CH2C H CH2CH3
CH2CH3

(R)-2-Bromobutane (S)-2-Butanol

Chapter 6 5
 2. The SN1 Mechanism

• Two step reaction with carbocation intermediate.

Step 1: Formation of carbocation (slow)

+ -
(CH3)3C Br (CH3)3C + Br
Carbocation
Step 2: Nucleophilic attack (fast)

Chapter 6 6
 SN1 Energy Diagram

• Two-step reaction.
• Two transition states and a carbocation
intermediate
Chapter 6 7
 Stereochemistry of SN1
Racemization:
inversion and retention

Chapter 6 8
 C. Factors influencing the reaction
Mechanism -- SN1 versus SN2

1.Structure of reactant

SN1: Order of carbocation stability

R H H H
R C+ > R C+ > H C+ > H C+
R R R H
Carbocation 3° > 2° > 1° > Methyl
stability:
Most stable Least stable

Chapter 6 9
 SN2: Steric Effect (Steric hindrance)

Hindrance increases, SN1 increases

Alkyl halides: 3¡ã 2¡ã 1¡ã CH3X
Hindrance decreases, SN2 increases
Chapter 6 10
 Propensity for SN1 or SN2 mechanism:

R3C Cl R2CH Cl RCH2 Cl CH3 Cl

3° 2° 1° Methyl
Alkyl SN 1 Mixed SN2 SN2
halides:
SN1 and SN2

Chapter 6 11
 2. Strength of Nucleophile

Strong nucleophiles favor SN2 processes

Reactivity: RO- > HO- >> RCOO- > ROH > H2O

3. Nature of Leaving Group

leaving group: I- > Br- > Cl- >> F-

R I > R Br > R Cl ( R F reacts so slowly that they

are seldom used in SN reactions.)
4. Solvent Polar
Polar solvent promote SN1 processes
Chapter 6 12
 SN 2 or SN1?
• One-step • Two-step
• Bimolecular; • Unimolecular;
Rate = k[halide][Nuc] Rate = k[halide]
• Inversion at chiral • Racemization of optically
carbon active compound
• Primary or methyl • Tertiary
• Strong nucleophile • Polar solvent

Chapter 6 13
6.4.2 Elimination Reactions

- -
C C + B: C C + X: + HB
H X

• The alkyl halide loses halogen as a halide ion,

and also loses H+ on the adjacent carbon to a
base.
• A π bond is formed. Product is alkene.
• Also called dehydrohalogenation (-HX).

Chapter 6 14
   CH3CH2OH
R – CH – CH2 + NaOH △ R – CH=CH2
H Br + NaBr + H2O

Elimination occurs only on a bromine atom

and a hydrogen atom attached on β carbon.
The premise is there must have hydrogen atom
attach to the β carbon atom.

Chapter 6 15
Zaitsev’s rule
CH3
   KOH EtOH
CH3 CH2 C CH3
Br
CH3 CH3
CH3CH C CH3 CH3CH2 C CH2
71% 29%
Eliminate H from the -C which have fewer
hydrogen atoms and give the more highly
substituted alkene products. “ the poor get
poorer”.
Chapter 6 16
 E2 Mechanism
H Br CH3
H -
H C C CH3 C C + H2O + Br
H H CH3
H CH3
O

• One-step mechanism
• Bimolecular elimination
• Requires a strong base
• Halide leaving and proton abstraction
happens simultaneously - no
intermediate.
Chapter 6 17
 E1 Mechanism
H Br H
H C C CH3 H C C CH3
H CH3 H CH3
H

H O H H CH3
+
C C + H 3O
H C C CH3
H CH3
H CH3
• Two-step mechanism
• Unimolecular elimination
• Halide ion leaves, forming carbocation.
• Base removes H+ from adjacent carbon.
• π bond forms.
Chapter 6 18
 Substitution or Elimination?
• Strong nuc. will go SN2 or E2.
• Primary halide usually SN2.
• Tertiary halide produce mixture of SN1, E1 or E2.
• Bulky bases favor elimination.
• Good nucleophiles, but weak bases, favor
substitution.
• High temperature favors elimination.
• SN2 reaction occurs in polar solvents like water.
• E2 reaction always take place in solvents with
lower polarity such as ethanol etc..

Chapter 6 19
 Example:
H2O
CH3CH2CH2OH
CH3 – CH – CH2 + NaOH C2H5OH
CH3CH=CH2
H Br

NaOC2H5
CH3CHCHCH2CH3 CH3C CHCH2CH3
C2H5OH
H3C Cl CH3

Chapter 6 20
 6.4.3 Reaction with Metals
produce Grignard reagent
Anhydrous ether
R X + Mg RMgX (Grignard reagent)

Nobel Prize
R= 1°,2°,3° alkyl, or aryl, or benzyl; （ 1912 ）

X=Cl, Br, or I.

Victor Grignard
(1871 ~ 1935)

Chapter 6 21
  
C MgX

H OH MgX(OH)

H OR' MgX(OR')
R MgX + O R H + O
H OCR' MgX(OCR')

H NR'(H)2 XMg NR'(H)2

R X RMgX R H

Chapter 6 22
 H+,H2O
RMgX + CO2 RCOOMgX RCOOH + Mg(OH)X

Grignard reagent can react with carbon dioxide

to prepare a carboxylic acid that has one more
carbon in the chain than in the R group Grignard
reagent offered.

End of Chapter 6 23
 Chapter 7

Alcohols, Phenols and Ethers

 Summary
R—OH CH3CH2OH
alcohol

Ar—OH OH
phenol

(Ar)R—O—R(Ar) CH3CH2OCH2CH3
ether
 7.1 Alcohols

3-8 % 10-15 % 30-60 %

% Ethanol by volume
1.1 Classification

CH3—OH Methyl (C has 3 H's)

RCH2—OH Primary(1°) (C has two H's, one R)

R2CH—OH Secondary (2°) (C has one H, two R's)

R3C—OH Tertiary (3°) (C has no H, 3 R's)

1.2 Nomenclature
Like other compounds, alcohols may have both
common and systematic names.
Common nomenclature:

CH3OH CH3CH2OH

Methyl alcohol Ethyl alcohol

Alcohols are called alkyl alcohol

1.2 Nomenclature
IUPAC systematic nomenclature:
Step 1 Determine and give the name of the
longest carbon chain containing the hydroxyl
group, replace the -e with -ol.
Step 2 Number the parent chain to give the
carbon bearing the hydroxyl group the
lowest possible number.
Step 3 Name and number all substituents as
prefixes to the alkanol name.
 1.2 Nomenclature

Formula IUPAC Common Name

CH4 methane
CH3─OH methanol methyl alcohol
CH3─CH3 ethane
1
CH3CH
─CH 2─OH
3─CH
ethanol
2─CH2─OH
ethyl alcohol
1-propanol
 2
CH3 CH2 CH OH
2—Butanol
1CH3

5 CH3
4 CH2
2 1
CH CH CH3
3
OH
3—Phenyl—2—pentanol
 Learning Check
Name the following alcohols according to IUPAC system

CH3 OH
CH3CHCH2CH2CHCH3

5-Methyl-2-hexanol
CHCH2CHCH2OH
CH3 CH3

2-Methyl-4-phenyl-1-pentanol
1.3 Physical Properties
Boiling point:
Alcohols
• contain polar OH
groups.
• can form hydrogen
bonds with other
alcohol or water
molecules.
• have higher boiling
points than alkanes
of similar mass.
• are more soluble in
water than alkanes.
1.4 Chemical Properties
A. Acidity of alcohols
1. Relative acidity

Acid H2O CH3OH CH3CH2OH (CH3)2CHOH

pKa 15.7 15.5 15.9 17.1

• Simple alcohols are about as acidic as water

• Alkyl groups make an alcohol a weaker acid
A. Acidity of alcohols
2. Reaction with Na
In the absence of water
R—OH + Na R—ONa + H2
When meet with water
R—ONa + H2O R—OH + NaOH
Reaction ability ：

Methyl ＞ Primary ＞ Secondary ＞ Tertiary

B. Dehydration of Alcohols (elimination)
Alcohols undergo
• dehydration when heated with an acid
catalyst.
• the loss of —H and —OH from adjacent
carbon atoms.
H OH
| | H+, heat
H—C—C—H H—C=C—H + H2O
| | | |
H H H H
alcohol alkene
B. Dehydration of Alcohols

CH3 – CH – CH2CH3 H2SO4

OH

CH3–CH=CH–CH3 + CH2=CH–CH2–CH3
2-Butene 1-Butene
Major product Minor product

Zaitsev’s rule:
the double bond is more highly substituted,
forming double bond with less H attached carbon
 Learning Check
Write the main product for the reaction of
2-Methyl-2-butanol when it undergoes
1. reaction with Na.
CH3 CH3
CH3CCH2CH3 + Na CH3CCH2CH3
OH ONa

2. dehydration.
CH3 CH3
CH3CCH2CH3 H2SO4
CH3C=CHCH3
OH
 C. Halogenation of Alcohols
(nucleophilic substitution reaction)
H+
R—OH + HBr R—Br + H2O
Reaction rates ：
Tertiary ＞ Secondary ＞ Primary
Lucas test:
Lucas reagent (HCl in ZnCl2 solution), used for
distinguishing alcohols. When alcohols react with
Lucas reagent, the produced alkyl halide is not
soluble and the solution becomes cloudy.
 ZnCl2 + HCl
(CH3)3C - OH (CH3)3C - Cl
R.T.
Tertiary Instantly

CH3CH2CHCH3 ZnCl2 + HCl CH3CH2CHCH3

OH heat Cl
Secondary 10 minutes

ZnCl2 + HCl
CH3(CH2)3OH CH3(CH2)3Cl
Primary heat No change
(Several hours)
 Learning Check
Distinguish the following compounds by simple
chemical test.
(1) 2,3-dimethyl-2-pentanol
(2) 3,3-dimethyl-1-pentanol
(3) 3-methyl-2-pentanol

1 cloudy immediately
Lucas reagent
2 no change
3 cloudy after heat 10 min
D. Oxidation of Alcohols

1. Oxidation and Reduction

• In an oxidation, there is an increase in the
number of C-O bonds. There is a loss of H.
• In a reduction, there is an decrease in the
number of C-O bonds. There is a gain of H.
 D. Oxidation of Alcohols
2. Oxidation of different alcohols

K2Cr2O7/H+ Overoxidation
RCH2OH RCHO RCOOH
aldehyde carboxylic acid
R – CH – R K2Cr2O7/H+
R2C=O ketone
OH
R
K2Cr2O7/H+
R–C–OH no product
R
 D. Oxidation of Alcohols
3. Oxidation of ethanol in the body
In the body,
• enzymes in the liver oxidize ethanol.
• aldehyde product impairs coordination.
• blood alcohol over 0.4% can be fatal.
O O
║ ║
• CH3CH2OH CH3CH CH3COH 2CO2 + H2O

ethanol acetaldehyde acetic acid

Effects of Alcohol on the Body
 Learning Check
Under K2Cr2O7/H+ condition, write the main
oxidation products of the following alcohols:
H CH3 O CH3
K2Cr2O7/H+
(1) CH3C CHCH3 CH3C CHCH3
OH
K2Cr2O7/H+
(2) CH3CH2CH2OH CH3CH2COOH

K2Cr2O7/H+
(3) OH O