3 Conversion of alcohols to alkyl halides (Route 1) 10.1 11.1
4 Conversion of alcohols to alkyl halides (Route 2) 10.2 11.2
5 Conversion of alcohols to sulfonate esters 10.3 11.3
6 Dehydration of alcohols 10.4 11.4
7 Redox reactions in organic chemistry
8 Oxidation of alcohols 10.5 11.5
9 Substitution reactions of ethers 10.6 11.6
10 Substitution reactions of epoxides (acidic conditions) 10.7 11.7
11 Substitution reactions of epoxides (neutral or basic conditions) 10.7 11.7
12 Crown ethers 10.10 11.7
13 Thiols and sulfides 10.11 11.11
Unit 4 lecture notes Page 2 of 34
Comprehensive list of learning objectives (Learning objectives form the basis for quiz and exam questions) So that you may assess your progress through the material of these lecture notes I provide the following “checklist” of learning objectives. As we move through the various Studies of these lecture notes we’ll see a re-listing of the corresponding learning objectives. At the conclusion of these lecture notes one should be able to, give the IUPAC names of alcohols and ethers predict whether or not a proposed carbocation rearrangement will occur (if it will you should be able to
give the ensuing carbocation; if it will not you should be able to explain why) give the mechanism (using curved arrow notation) of carbocation rearrangement give an example of, or identify, a 1,2-hydride shift give an example of, or identify, a 1,2-alkyl shift invoke carbocation rearrangements when warranted give the organic product(s) that arise from the reaction* between an alcohol and HCl, HBr or HI predict the distribution of organic product(s) that arise from the reaction* between an alcohol and HCl,
HBr or HI explain the distribution of organic product(s) that arise from the reaction* between an alcohol and HCl,
HBr or HI give the mechanism (using curved arrow notation) for the reaction* between an alcohol and HCl, HBr or
HI give the organic product(s) that arise from the reaction** between an alcohol and PBr3, PCl3 or PI3 predict the distribution of organic product(s) that arise from the reaction** between an alcohol and PBr3,
PCl3 or PI3 explain the distribution of organic product(s) that arise from the reaction** between an alcohol and PBr3,
PCl3 or PI3 give the mechanism (using curved arrow notation) for the reaction** between an alcohol and PBr3, PCl3
or PI3 state the advantages of Route 2 over Route 1 as a method for the conversion of alcohols to alkyl halides give the organic product(s) that arise from the reaction** between an alcohol and a sulfonyl chloride predict the distribution of organic product(s) that arise from the reaction** between an alcohol and a
sulfonyl chloride explain the distribution of organic product(s) that arise from the reaction** between an alcohol and a
sulfonyl chloride give the mechanism (using curved arrow notation) for the reaction** between an alcohol and a sulfonyl
chloride a) state that the dehydration of a primary alcohol proceeds via the E2 pathway b) state that the dehydration* of a secondary alcohol proceeds via the E1 pathway c) state that the dehydration* of a tertiary alcohol proceeds via the E1 pathway d) give the organic product(s) that arise from the dehydration* of an alcohol e) explain why acid (either sulfuric acid or phosphoric acid) is required f) give the reaction conditions one would employ to effect the complete dehydration of an alcohol g) predict the distribution of organic product(s) that arise from the acid-catalyzed dehydration* of an alcohol h) explain the distribution of organic product(s) that arise from the dehydration* of an alcohol i) give the mechanism (using curved arrow notation) for the dehydration* of an alcohol j) recognize whether an organic compound has been oxidized, reduced or neither, in a given reaction a) state that the treatment of methanol with aqueous chromic acid yields formic acid b) state that the treatment of a primary alcohol with aqueous chromic acid yields a carboxylic acid c) state that the treatment of a secondary alcohol with aqueous chromic acid yields a ketone d) state that the treatment of methanol with PCC in anhydrous dichloromethane (CH2Cl2) yields
formaldehyde
Unit 4 lecture notes Page 3 of 34
e) state that the treatment of a primary alcohol with PCC in anhydrous dichloromethane (CH2Cl2) yields an aldehyde
f) state that the treatment of a secondary alcohol with PCC in anhydrous dichloromethane (CH2Cl2) yields a ketone
g) give the various combinations of reagents that give aqueous chromic acid (aq H2CrO4) h) predict the organic product(s) that arise from the reaction between an alcohol and chromic acid i) predict the organic product(s) that arise from the reaction between an alcohol and PCC in anhydrous
dichloromethane a) give the organic product(s) that arise from the reaction* between an ether and HCl, HBr or HI b) predict the distribution of organic product(s) that arise from the reaction* between an ether and HCl, HBr
or HI c) explain the distribution of organic product(s) that arise from the reaction* between an ether and HCl, HBr
or HI d) give the mechanism (using curved arrow notation) for the reaction* between an ether and HCl, HBr or HI a) give the organic product(s) that arise from the substitution reactions of epoxides under acidic conditions b) predict the distribution of organic product(s) that arise from the substitution reactions of epoxides under
acidic conditions c) explain the distribution of organic product(s) that arise from the substitution reactions of epoxides under
acidic conditions d) give the mechanism (using curved arrow notation) for the substitution reactions of epoxides under acidic
conditions a) give the organic product(s) that arise from the substitution reactions of epoxides under neutral or basic
conditions b) predict the distribution of organic product(s) that arise from the substitution reactions of epoxides under
neutral or basic conditions c) explain the distribution of organic product(s) that arise from the substitution reactions of epoxides under
neutral or basic conditions d) give the mechanism (using curved arrow notation) for the substitution reactions of epoxides under
neutral or basic conditions
* carbocations involved, therefore one or more carbocation rearrangements may occur (following the rules in Study 2)
**in the presence of pyridine
Unit 4 lecture notes Page 4 of 34
Study 1 Independent study of nomenclature of alcohols and ethers
Introduction This independent Study examines the IUPAC system for naming alcohols and ethers Bruice 6th section(s) 2.5, 2.6 Bruice 7th section(s) 3.5, 3.6 Learning objective(s) At the conclusion of this independent Study one should be able to give the IUPAC
names of alcohols and ethers.
Study 2 Carbocation rearrangements
Introduction This Study reviews carbocation rearrangements are discussed in Chemistry 331. Carbocation rearrangements occur in certain alcohol reactions.
Bruice 6th section(s) 4.7 Bruice 7th section(s) 6.7 Learning objective(s) At the conclusion of this Study one should be able to,
a) predict whether or not a proposed carbocation rearrangement will occur (if it will you should be able to give the ensuing carbocation; if it will not you should be able to explain why)
b) give the mechanism (using curved arrow notation) of carbocation rearrangement c) give an example of, or identify, a 1,2-hydride shift d) give an example of, or identify, a 1,2-alkyl shift e) invoke carbocation rearrangements when warranted
Whenever a carbocation is involved in an organic reaction, we need to consider the possibility that one or more carbocation rearrangements may occur. Rules governing carbocation rearrangements -as a general rule a 1,2-shift of hydride will occur if it results in a more stable carbocation -as a general rule a 1,2-shift of an alkyl group (e.g. methyl, ethyl, propyl, or any other type of alkyl group for that matter) will occur if it results in a more stable carbocation
Unit 4 lecture notes Page 5 of 34
Rule 1 A carbocation rearrangement that leads to a more stable carbocation will occur -i.e. primary (1°) to secondary (2°); primary (1°) to tertiary (3°); secondary (2°) to tertiary (3°)
e.g.
H
CC CH2CH2CH2CH3
H
C
CH2CH2CH2CH3
H
H
CH3
a secondary (2o) carbocation
CC CH2CH2CH2CH3
H
C
CH2CH2CH2CH3
H
H
CH3
a tertiary (3o) carbocation
H
1,2-hydride shift
ALLOWED
CH3
CC CH2CH2CH2CH3
H
C
CH2CH2CH2CH3
H
H
CH3
a secondary (2o) carbocation
CC CH2CH2CH2CH3
H
C
CH2CH2CH2CH3
H
H
CH3
a tertiary (3o) carbocation
CH3
1,2-metthyl shift
ALLOWED
CH3
CC CH2CH2CH2CH3
H
C
CH2CH2CH2CH3
H
H
CH3
a secondary (2o) carbocation
CC CH3
H
C
CH2CH2CH2CH3
H
H
CH3
a tertiary (3o) carbocation
CH2CH2CH2CH3
1,2-butyl shift
ALLOWED
Rule 2 A carbocation rearrangement that leads to a less stable carbocation will not occur
-i.e. 3° to 1°; 3° to 2°; 2° to 1°
e.g.
1,2-hydride shift
H
CC CH2CH2CH2CH3
H
C
CH2CH2CH2CH3
H
H
H
a secondary (2o) carbocation
H
CC CH2CH2CH2CH3
H
C
CH2CH2CH2CH3H
H
a primary (1o) carbocation
H
NO
T A
LLO
WED
Unit 4 lecture notes Page 6 of 34
Rule 3 A carbocation rearrangement that leads to a different carbocation of the same class will not occur -i.e. 1° to 1°; 2° to 2°; 3° to 3°
e.g.
H
CC CH2CH2CH2CH3
H
C
CH2CH2CH2CH3
H
H
CH3
a secondary (2o) carbocation
CC CH2CH2CH2CH3
CH2CH2CH2CH3
C
H
H
CH3
a secondary (2o) carbocation
H H
1,2-butyl shift
(a type of1,2-alkyl shift)
NO
T A
LLO
WED
NO
T A
LLO
WED
H
CC CH2CH2CH2CH3
H
C
CH2CH2CH2CH3
H
H
CH3
a secondary (2o) carbocation
CC CH2CH2CH2CH3
H
C
CH2CH2CH2CH3H
CH3
a secondary (2o) carbocation
H
1,2-hydride shift
H
Rule 4 Rules 2 and 3 are overridden whenever the carbocation rearrangement leads to a reduction in ring strain e.g.
a secondary (2o) carbocation
H
CH3
H
1,2-alkyl shift
(Cd migrates from
Ca to Ce)
ab
c
d
e ab
cd
eH
H
CH3
ALLOWED a secondary (2o) carbocation
1,2-hydride shift
ALLOWED
ab
cd
e
H
CH3
H
highly strained four-membered ring much less strained five-membered ring
Unit 4 lecture notes Page 7 of 34
Study 3 Conversion of alcohols to alkyl halides (Route 1)
Introduction This Study examines the conversion of an alcohol to an alkyl halide through treatment with HCl, HBr or HI. We will consider a number of important questions. How do these reactions occur? What products are formed? Why are some products the major products while others are the minor products? Is there a discernible pattern to this type of reaction and can it be used as a reliable predictor for reaction outcomes?
H
C C
X
HX
H
C C
OH
Bruice 6th section(s) 10.1 Bruice 7th section(s) 11.1 Learning objective(s) At the conclusion of this Study one should be able to,
a) give the organic product(s) that arise from the reaction* between an alcohol and HCl, HBr or HI
b) predict the distribution of organic product(s) that arise from the reaction* between an alcohol and HCl, HBr or HI
c) explain the distribution of organic product(s) that arise from the reaction* between an alcohol and HCl, HBr or HI
d) give the mechanism (using curved arrow notation) for the reaction* between an alcohol and HCl, HBr or HI * carbocations involved, therefore one or more carbocation rearrangements may occur (following the rules in Study 2)
Unit 4 lecture notes Page 8 of 34
Overview of Route 1
HCl, HBr, HI
R OH
R O
H
H
SN2 pathway, if alcohol is
.
carbocation
invoke appropriate rearrangements
R X
hydroxide is apoor leaving group
water is agood leaving group
SN1 pathway, if alcohol is
.
R X
X
Relevant alcohols
CH3OH, methanol
RCH2OH, a primary (10) alcohol
R2CHOH, a secondary (20) alcohol
R3COH, a tertiary (30) alcohol
Problem solving strategy
1. Identify the type of alcohol
2. Select pathway (SN1 or SN2)
3. Use reaction mechanism to determine product(s)
Let’s take a look at a few worked examples
HI
HO
HBr
OH
Unit 4 lecture notes Page 9 of 34
OH
HCl
H
Unit 4 lecture notes Page 10 of 34
HBrC
OH
CH3
CH3
CH3OHHBr
CH3BrMg in dry
diethyl ether
CH3MgBr
O
1
in diethyl ether
2. H3O+
CH3CH2CH2OH
no direct path
MAKING CONNECTIONS
Unit 4 lecture notes Page 11 of 34
Study 4 Conversion of alcohols to alkyl halides (Route 2)
Introduction This Study examines the conversion of an alcohol to an alkyl halide through treatment with PBr3, PCl3 or PI3 (in the presence of pyridine). We will consider a number of important questions. How do these reactions occur? What products are formed? Is there a discernible pattern to this type of reaction and can it be used as a reliable predictor for reaction outcomes?
H
C C
XH
C C
OH
PBr3, PCl3 or PI3
and pyridine
(as solvent and as
proton scavenger)
Bruice 6th section(s) 10.2 Bruice 7th section(s) 11.2 Learning objective(s) At the conclusion of this Study one should be able to,
a) predict the distribution of organic product(s) that arise from the reaction* between an alcohol and PBr3, PCl3 or PI3
b) explain the distribution of organic product(s) that arise from the reaction* between an alcohol and PBr3, PCl3 or PI3
c) give the mechanism (using curved arrow notation) for the reaction* between an alcohol and PBr3, PCl3 or PI3
d) state the advantages of Route 2 over Route 1 as a method for the conversion of alcohols to alkyl halides
*in the presence of pyridine
Unit 4 lecture notes Page 12 of 34
Overview of Route 2
R OH
R O
Reaction occurs if alcohol is
.
R X
hydroxide is apoor leaving group
a halophosphite group whichis a good leaving group
X
Relevant alcohols
CH3OH, methanol
RCH2OH, a primary (10) alcohol
R2CHOH, a secondary (20) alcohol
R3COH, a tertiary (30) alcohol
Problem solving strategy
1. Identify the type of alcohol
2. Decide if alcohol will react
3. Use reaction mechanism to determine product
a phosphorus trihalidePX3
P
X
X
X
Reaction does not occur if alcohol is
.
in pyridine (solvent and proton scavenger)
Let’s take a look at a few worked examples
PCl3, pyridineC
OH
CH3
CH3
OH
PBr3, pyridine
H
PCl3, pyridine
OH
Unit 4 lecture notes Page 13 of 34
Li in dry
hexane
no direct path
OH
PBr3, pyridine
Br LiO
1
in diethyl ether
2. H3O+
OH
MAKING CONNECTIONS
Study 5 Conversion of alcohols to alkyl sulfonate esters
Introduction This Study examines the conversion of an alcohol to an alkyl sulfonate ester through treatment with a sulfonyl chloride (in the presence of pyridine). We will consider a number of important questions. How do these reactions occur? What products are formed? Is there a discernible pattern to this type of reaction and can it be used as a reliable predictor for reaction outcomes?
H
C C
OSO2R'H
C C
OH
pyridine
(as solvent and asproton scavenger)
Cl S
O
O
R1
Bruice 6th section(s) 10.3 Bruice 7th section(s) 11.3 Learning objective(s) At the conclusion of this Study one should be able to,
a) give the organic product(s) that arise from the reaction* between an alcohol and a sulfonyl chloride
b) predict the distribution of organic product(s) that arise from the reaction* between an alcohol and a sulfonyl chloride
c) explain the distribution of organic product(s) that arise from the reaction* between an alcohol and a sulfonyl chloride
d) give the mechanism (using curved arrow notation) for the reaction* between an alcohol and a sulfonyl chloride *in the presence of pyridine
Unit 4 lecture notes Page 14 of 34
Overview of alkyl sulfonate ester formation
R OHhydroxide is a
poor leaving group
excellent leaving group(100 times better than chloride ion!!)
a para-toluenesulfonate ester(a tosylate)(aka ROTs)
CH3 S
O
O
OR
a methanesulfonate ester(a mesylate)(aka ROMs)
CF3 S
O
O
OR
a trifluoromethanesulfonate ester(a triflate)(aka ROTf)
Unit 4 lecture notes Page 15 of 34
Let’s take a look at a few worked examples
OH
MsCl, pyridine
TsCl (1 mole), pyridine
OH
OH
1 mole
Alkyl sulfonate esters in synthesis
MsCl, in pyridineCH3CH2CN
no direct path
MAKING CONNECTIONSNaCN, DMSO, heat
from CH 331
CH3CH2OH CH3CH2OMs
TsCl, in pyridineCH3CH2SCH3
no direct path
MAKING CONNECTIONSNaSCH3, DMSO, heat
from CH 331
CH3CH2OH CH3CH2OTs
Unit 4 lecture notes Page 16 of 34
Study 6 Dehydration of alcohols
Introduction This Study examines the acid-catalyzed dehydration of alcohols. We will consider a number of important questions. How do these reactions occur? What products are formed? Why are some products the major products while others are the minor products? Is there a discernible pattern to this type of reaction and can it be used as a reliable predictor for reaction outcomes?
H2SO4 (or H3PO4)
heat
H
C C
OH
Bruice 6th section(s) 10.4 Bruice 7th section(s) 11.4 Learning objective(s) At the conclusion of this Study one should be able to,
a) state that the dehydration of a primary alcohol proceeds via the E2 pathway b) state that the dehydration* of a secondary alcohol proceeds via the E1 pathway c) state that the dehydration* of a tertiary alcohol proceeds via the E1 pathway d) give the organic product(s) that arise from the dehydration* of an alcohol e) explain why acid (either sulfuric acid or phosphoric acid) is required f) give the reaction conditions one would employ to effect the complete dehydration
of an alcohol g) predict the distribution of organic product(s) that arise from the acid-catalyzed
dehydration* of an alcohol h) explain the distribution of organic product(s) that arise from the dehydration* of an
alcohol i) give the mechanism (using curved arrow notation) for the dehydration* of an
alcohol * carbocations involved, therefore one or more carbocation rearrangements may occur (following the rules in Study 2)
Unit 4 lecture notes Page 17 of 34
Overview of alcohol dehydration
R OH
R O
H
H
E2 pathway, if alcohol is
.
carbocation
invoke appropriate rearrangements
hydroxide is apoor leaving group
water is agood leaving group
E1 pathway, if alcohol is
.
Relevant alcohols
CH3OH, methanol
RCH2OH, a primary (10) alcohol
R2CHOH, a secondary (20) alcohol
R3COH, a tertiary (30) alcohol
Problem solving strategy
1. Identify the type of alcohol
2. Select pathway (E1 or E2)
3. Use reaction mechanism to determine product(s)
H2SO4 (or H3PO4)
OSO3H
Conditions employed to effect the complete dehydration of an alcohol
Unit 4 lecture notes Page 18 of 34
Predicting the distribution of alkene products
-relative stabilities of a few alkenes (data from: J.D. Rockenfeller, F.D. Rossini Journal of Physical Chemistry, 1961, p267)
e.g. e.g.
Hhydrogenation
= -28.0 kcal/mole
energy
Hhydrogenation
= -26.9 kcal/mole
Hhydrogenation
= -28.0 kcal/mole
energy
Hhydrogenation
= -26.5 kcal/mole
R
R
R
R
>
R
R
R
H
>
R
R
H
H
>
R
H
R
H
H
R
R
H
>
H
H
R
H
>
H
H
H
H
tetra-substituted
alkenes
tri- substituted
alkenes
di- substituted
alkenes
di- substituted
alkenes
mono- substituted
alkenes
ethylene
most stable alkene
least stable alkene
Unit 4 lecture notes Page 19 of 34
Let’s take a look at a few worked examples
OH H2SO4, heat
H2SO4, heat
OH
Unit 4 lecture notes Page 20 of 34
H2SO4, heat
OH
Unit 4 lecture notes Page 21 of 34
Study 7 Redox reactions in organic chemistry Introduction This unit examines the method for determining whether an organic compound has
been oxidized, reduced or neither, in a given reaction Bruice section(s) N/A Learning objective(s) At the conclusion of this Study one should be able to recognize whether an organic
compound has been oxidized, reduced or neither, in a given reaction
How does one decide whether an organic compound has been reduced or oxidized?
Step 1 Begin by calculating oxidation levels for the reactant and product
-where A represents an atom that is more electronegative than carbon; where B represents an atom that is less electronegative than carbon
Step 2 If the net change in oxidation levels is positive then the reactant has been oxidized
If the net change in oxidation levels is negative then the reactant has been reduced
If there is no net change in oxidation levels then the reactant has neither been reduced nor oxidized
Let’s look at a few examples
Oxidation level of Net change in oxidation
level
Reactant has been
reactant product
a)
O
O
O
Oxidized
Reduced
Neither oxidized nor reduced
b)
F
Oxidized
Reduced
Neither oxidized nor reduced
c)
Oxidized
Reduced
Neither oxidized nor reduced
Unit 4 lecture notes Page 22 of 34
Study 8 Oxidation of alcohols
Introduction This Study examines the oxidations of alcohols. We will consider a number of important questions. How do these reactions occur? What products are formed? Is there a discernible pattern to this type of reaction and can it be used as a reliable predictor for reaction outcomes?
R CH2OH
O
CR H
O
CR OH
R CH
O
CR R
O
CR R
R
OH
a primary alcohol
a secondary alcohol
an aldehyde
a carboxylic acid
a ketone
a ketone
Bruice 6th section(s) 10.5 Bruice 7th section(s) 11.5 Learning objective(s) At the conclusion of this Study one should be able to,
a) state that the treatment of methanol with aqueous chromic acid yields formic acid b) state that the treatment of a primary alcohol with aqueous chromic acid yields a
carboxylic acid c) state that the treatment of a secondary alcohol with aqueous chromic acid yields a
ketone d) state that the treatment of methanol with PCC in anhydrous dichloromethane
(CH2Cl2) yields formaldehyde e) state that the treatment of a primary alcohol with PCC in anhydrous
dichloromethane (CH2Cl2) yields an aldehyde f) state that the treatment of a secondary alcohol with PCC in anhydrous
dichloromethane (CH2Cl2) yields a ketone g) give the various combinations of reagents that give aqueous chromic acid (aq
H2CrO4) h) predict the organic product(s) that arise from the reaction between an alcohol and
chromic acid i) predict the organic product(s) that arise from the reaction between an alcohol and
Introduction This Study examines the substitution reactions of ethers. We will consider a number of important questions. How do these reactions occur? What products are formed? Is there a discernible pattern to this type of reaction and can it be used as a reliable predictor for reaction outcomes?
2 HXR O R' R X R' X
Bruice 6th section(s) 10.6 Bruice 7th section(s) 11.6 Learning objective(s) At the conclusion of this Study one should be able to,
a) give the organic product(s) that arise from the reaction* between an ether and HCl, HBr or HI
b) predict the distribution of organic product(s) that arise from the reaction* between an ether and HCl, HBr or HI
c) explain the distribution of organic product(s) that arise from the reaction* between an ether and HCl, HBr or HI
d) give the mechanism (using curved arrow notation) for the reaction* between an ether and HCl, HBr or HI * carbocations may be involved, therefore one or more carbocation rearrangements may occur (following the rules in Study 2)
Unit 4 lecture notes Page 26 of 34
An overview
2 HX (HCl, HBr or HI)
R OR
R O
H
R
SN2 pathway, if the R group is
.
carbocation
invoke appropriate rearrangements
R X
alkoxides arepoor leaving groups
alcohols aregood leaving groupsX
SN1 pathway, if the R group is
.
R X
R X R X
Unit 4 lecture notes Page 27 of 34
Let’s take a look at a few examples
O HI
HBr
O
Unit 4 lecture notes Page 28 of 34
Study 10 Substitution reactions of epoxides under acidic conditions
Introduction This Study examines the substitution reactions of epoxides under acidic conditions. We will consider a number of important questions. How do these reactions occur? What products are formed? Is there a discernible pattern to this type of reaction and can it be used as a reliable predictor for reaction outcomes?
Bruice 6th section(s) 10.7 Bruice 7th section(s) 11.7 Learning objective(s) At the conclusion of this Study one should be able to,
a) give the organic product(s) that arise from the substitution reactions of epoxides under acidic conditions
b) predict the distribution of organic product(s) that arise from the substitution reactions of epoxides under acidic conditions
c) explain the distribution of organic product(s) that arise from the substitution reactions of epoxides under acidic conditions
d) give the mechanism (using curved arrow notation) for the substitution reactions of epoxides under acidic conditions
Let’s take a look at a few examples
Unit 4 lecture notes Page 29 of 34
Unit 4 lecture notes Page 30 of 34
Study 11 Substitution reactions of epoxides under neutral or basic conditions
Introduction This Study examines the substitution reactions of epoxides under neutral or basic conditions. We will consider a number of important questions. How do these reactions occur? What products are formed? Is there a discernible pattern to this type of reaction and can it be used as a reliable predictor for reaction outcomes?
Bruice 6th section(s) 10.7 Bruice 7th section(s) 11.7 Learning objective(s) At the conclusion of this Study one should be able to,
a) give the organic product(s) that arise from the substitution reactions of epoxides under neutral or basic conditions
b) predict the distribution of organic product(s) that arise from the substitution reactions of epoxides under neutral or basic conditions
c) explain the distribution of organic product(s) that arise from the substitution reactions of epoxides under neutral or basic conditions
d) give the mechanism (using curved arrow notation) for the substitution reactions of epoxides under neutral or basic conditions
Let’s take a look at a few examples
i)
O
H
H
1. NaN3
2. H3O+
Na+ as counter ion
N3 as nucleophile
a
b
Ca is a secondary center and thus suited to SN2 attack
Cb is a secondary center and thus suited to SN2 attack
Ca and Cb are equally likely to be attacked. This leads to
equal amounts of the products shown.
OH
H
H
N3
H
OH
N3
H
formed in equal amounts (as a racemic mixture)
Reaction mechanism for the formation of first product
O
H
H
a
b
N3
O
H
H
N3
H3O+ OH
H
H
N3The nucleophile attacks from the side opposite
the epoxide ring (note the inversion of configuration at Ca)
Na+
Na+
a
b
a
b
Unit 4 lecture notes Page 31 of 34
ii)
1. NaOCH3
2. H3O+
Na+ as counter ion
OCH3 as nucleophile
a
b
Ca is a tertiary center and thus not suited to SN2 attack
Cb is a primary center and thus suited to SN2 attack
product arises solely from attack at Cb
Reaction mechanism
H3O+
Na+
O
ab
O
OCH3
CH2OCH3
ONa+
CH2OCH3
OH
CH2OCH3
OH
sole organic product
a
b
a
b
iii)
CH3Li, dry ether
2. H3O+
Li+ as counter ion
CH3 as nucleophile
a
b
Ca is a secondary center and thus suited to SN2 attack
Cb is a primary center and thus suited to SN2 attack
Greater steric hindrance associated with attack at Ca.
Therefore the major organic product arises from attack at Cb
H3O+
O
CH2CH3
OH
HH
CH2OH
H
CH3
major organic product minor organic product
Reaction mechanism for the formation of first product
O
H
CH3
a
b CH2CH3
O
H
Li+
Li+
CH2CH3
OH
H
H3O+
Reaction mechanism for the formation of second product
O
H
CH3
a
b CH2O
H
CH3
Li+
Li+
CH2OH
H
CH3
a
b
a
b
a
b
a
b
Unit 4 lecture notes Page 32 of 34
Study 12 Crown ethers
Introduction This Study is a brief survey of crown ethers. Bruice 6th section(s) 10.10 Bruice 7th section(s) 11.7 Learning objective(s) This Study is included for informational purposes only. You will not be tested on
Study 12 Crown ethers are a class of cyclic compounds that possess an array of ether groups about a central cavity. Certain crown ethers are able to form inclusion compounds.
e.g.
O
O O
O
[12]-crown-4
Li
O
O O
O
Li bound in [12]-crown-4
Li
For an interesting discussion of the link between nonactin’s ability to act like a crown ether and its antibiotic behavior please see Bruice page 440.
Study 13 Thiols and sulfides
Introduction This Study is a brief survey of thiols and sulfides. Bruice 6th section(s) 10.11 Bruice 7th section(s) 11.11 Learning objective(s) This Study is included for informational purposes only. You will not be tested on
Study 13.
Thiols
Thiols are also known as mercaptans Thiols are sulfur analogues of alcohols
e.g.
SH SH
Unit 4 lecture notes Page 33 of 34
The amino acid cysteine (shown below) contains a thiol
H3N CH C
CH2
OH
O
SH Thiols (pKa ~ 10) are stronger acids than alcohols (pka ~ 15) since thiolate ions are more stable than alkoxide ions.
SH S
a thiol a thiolate ion
NaHNa
Thiolate ions are good nucleophiles
S
a thiolate ion
CH3Br,
DMSO, heatSCH3
a sulfide
Sulfides Sulfides are also known as thioethers Sulfides are sulfur analogues of ethers
Sulfides are good nucleophiles
CH3CH2Br,
DMSO, heat
SCH3
a sulfide
SCH3
a sulfonium salt
CH2CH3
Br
Unit 4 lecture notes Page 34 of 34
Although the following assigned questions are not turned in they provide an excellent opportunity for you to assess your progress through the course material. Assigned questions Correlated to Bruice 6th and Bruice 7th
Bruice 6th Bruice 7th
Bruice 6th Bruice 7th
Bruice 6th Bruice 7th 2.18a 3.20a 10.12c 11.15a 10.33(all but g) 11.48(all but g)
