LMZ/CHEM109A/ Winter 2010

Chapter 10: Reactions of alcohols, amines, ethers, epoxides and sulfur-containing

compounds
I. Nucleophilic substitution reactions for the conversion of alcohols to other
functional groups
A. Introduction:

4. Reaction of alcohols (especially 1 or 2) with phosphorus halide (Sec. 11.8)

R
R
PCl3, PBr3, or PCl5
(+ HOPX2
R'
R'
H
X
X= Br or Cl)
OH
H
inversion for 1 and 2 C
R' = H or alkyl or aryl
(Note: For the synthesis of alkyl chloride, thionyl chloride generally gives better
yields than PCl3 or PCl5.)
Mechanism (for reaction with PBr3)?

B. Conversion of alcohol to alkyl halide (Reaction at C-O bond) (sec. 11.1): in-situ
converting OH into good leaving groups
1. Conversion of alcohol to alkyl bromide by reaction with HBr (or NaBr, H2SO4)
R* Br + H2O
R* OH + HBr
R* OH + HBr
R* Br + H2O
1
S
N
SN2 inversion
3
racemic
1
mixture
Mechanism?

e.g. 1

OH
C

H3 C

PBr3
CH2CH3

C. Conversion of alcohols to tosylate (Reaction at O-H bond) (Sec. 10.3)

2. Conversion of alcohol to alkyl chloride by reaction with Lucas reagent (HCl,
ZnCl2)
ZnCl2 *
ZnCl2
R* Cl + H2O
R* OH + HCl
R* OH + HCl
R Cl + H2O
1
S
N
SN2 inversion
3
racemic
1
mixture
Mechanism?

R
O
R'
Cl S
CH3
H O
O
O S
tosyl chloride (p-TosCl)
O
tosylate
retension
NEt or pyridine

R
R'
H
OH
R' = H or alkyl
or aryl

e.g. 2
Me

OH
C

CH3 + NEt3HCl
(or pyridinum
chloride)

O
Cl S
O

CH3
pyridine

Et

D. Conversion of alcohol to other functional groups via halides or tosylates:

Stereochemical consequences (sec/ 10.3)
R'

3. Reaction of alcohols (especially 1 or 2) with thionyl chloride (Sec. 11.9)

R
R'

SOCl2

H
OH
R' = H or alkyl or aryl

Mechanism?

H
OH

PCl3or PBr3

X + H2 O
H
inversion
R'

Nu e.g. N3
SN 2

R'

inversion

H
Nu

double inversion : overall retention

R
R'

(+ SO2 + HCl)

X
H
stereochemistry??

O
R
Cl S
R'
H
O
O-H

R
CH3 R'
(p-TosCl)

H + HCl
OTos
retension

Nu e.g. N3
SN2

R
R'

Nu

inversion H

retension + inversion : overall inversion

LMZ/CHEM109A/ Winter 2010

II. Elimination and rearrangement reactions of alcohols

1. Acid catalyzed dehydration of alcohol to alkene (Sec. 10.4)
(3>2>1)

III. Oxidation of alcohols, aldehydes, and thiols

A. Oxidation of alcohols and aldehydes (Sec. 10.5)
a. Oxidation of 1 alcohols to aldehydes or carboxylic acids
[O], oxidation

OH

R C

[O], oxidation

N H
H
CrO3Cl
aldehyde
1 alcohol (CrO , pyridine, HCl)
3

mechanism?

pyridinium
chlorochromate (PCC)

e.g. Na2Cr2O7, H2O,

R
OH
ethanol
carboxylic acid
Or Jone's reagent
(CrO3, H3O+, acetone)
OR KMnO4, H2O

[O] e.g. Na2Cr2O7, H2O, ethanol, OR CrO3, H3O+, acetone, (OR KMnO4, H2O)

b. Oxidation of 2 alcohols to ketones

OH

R C

- carbocation rearrangement may occur

[O], oxidation

H
2 alcohol

e.g. PCC, CH2Cl2

OR Na2Cr2O7, H2O, ethanol
OR CrO3, H3O+, acetone

[O]

R'
R

R'

no further
oxidation

ketone

c. 3 alcohols cannot be oxidized

OH

R C

[O], oxidation
R'

R"
3 alcohol

NO REACTION

- SN2 reaction competes with E2 dehydration

mechanism:

2. Dehydration by POCl3
IV. Amines as organic bases (sec. 10.6)
- amino (NH2- or NR2-) is a very poor leaving group;
- amines does not undergo elimination or substitution reactions on the C-N bond.

- as base

LMZ/CHEM109A/ Winter 2010

V. Nucleophilic substitution reactions of ethers (ROR)

A. RO- is poor leaving groups similar to OH-: need acid activation
- reaction proceeds with neither pure SN2 or SN1.
- regioselectivity:

B. SN1 or SN2 mechanism (PCl3 or TsCl not working)

D. basic conditions:

- regioselectivity controlled by sterics

- stereochemistry: SN2

VI. Epoxide (one kind of ether) ring opening (sec. 10.8)

A. Due to ring strain, much more reactive than normal ethers
VII. Crown ethers
- help dissolve metal cations
- Na+ --- [15]-crown-5
- K+ -----[18]-crown-6
- Li+ ----[12]-crown-4

B. under acidic conditions-- opened by halide, even H2O and ROH

LMZ/CHEM109A/ Winter 2010

IX. Thiols, sulfide (sec. 10.11)

B. Organolithium compounds: prepared in alkanes

- strongly basic (pKa >40), can be nucleophile as well
- C-Li bond: polarized covalent bond (not ionic bond)

A. naming thiols
- as the principle functional group, alkane + thiol (similar to alcohol case)

- naming priority: OH>SH>NH2, when treated as substituent, use 'mercapto'

C. Organomagnesium compounds -- Grignard reagents (in ethereal solvent)

- strongly basic, but less reactive than corresponding lithium compounds.
- C-Mg bond: polarized covalent bond, not ionic bond.

B. naming sulfide: (similar to ether)

C. Strong nucleophiles due to high polarizability (softness)

D. Reactions:

X. Organometallic compounds (sec. 10.12)

A. compare: