Chemistry 332 Lecture Notes

Unit 4 Alcohols, ethers and epoxides

Introduction These lecture notes examine a variety of alcohol, ether and epoxide reactions. Overview Study
1 2 3 4 5 6 7 8 9 10 11 12 13 Nomenclature of alcohols and ethers Carbocation rearrangements Conversion of alcohols to alkyl halides (Route 1) Conversion of alcohols to alkyl halides (Route 2) Conversion of alcohols to sulfonate esters Dehydration of alcohols Redox reactions in organic chemistry Oxidation of alcohols Substitution reactions of ethers Substitution reactions of epoxides (acidic conditions) Crown ethers Thiols and sulfides 10.5 10.6 10.7 10.10 10.11 11.5 11.6 11.7 11.7 11.7 11.11

Bruice 6th sections

2.5, 2.6 4.7 (from CH 331) 10.1 10.2 10.3 10.4

Bruice 7th sections

3.5, 3.6 6.7 (from CH 331) 11.1 11.2 11.3 11.4

Substitution reactions of epoxides (neutral or basic conditions) 10.7

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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 well 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 (CH 2Cl2) yields formaldehyde

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e) f) g) h) i) a) b) c) d) a) b) c) d) a) b) c) d)

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state that the treatment of a primary alcohol with PCC in anhydrous dichloromethane (CH2Cl2) yields an aldehyde state that the treatment of a secondary alcohol with PCC in anhydrous dichloromethane (CH2Cl2) yields a ketone give the various combinations of reagents that give aqueous chromic acid (aq H2CrO4) predict the organic product(s) that arise from the reaction between an alcohol and chromic acid predict the organic product(s) that arise from the reaction between an alcohol and PCC in anhydrous dichloromethane give the organic product(s) that arise from the reaction* between an ether and HCl, HBr or HI predict the distribution of organic product(s) that arise from the reaction* between an ether and HCl, HBr or HI explain the distribution of organic product(s) that arise from the reaction* between an ether and HCl, HBr or HI give the mechanism (using curved arrow notation) for the reaction* between an ether and HCl, HBr or HI give the organic product(s) that arise from the substitution reactions of epoxides under acidic conditions predict the distribution of organic product(s) that arise from the substitution reactions of epoxides under acidic conditions explain the distribution of organic product(s) that arise from the substitution reactions of epoxides under acidic conditions give the mechanism (using curved arrow notation) for the substitution reactions of epoxides under acidic conditions give the organic product(s) that arise from the substitution reactions of epoxides under neutral or basic conditions predict the distribution of organic product(s) that arise from the substitution reactions of epoxides under neutral or basic conditions explain the distribution of organic product(s) that arise from the substitution reactions of epoxides under neutral or basic conditions 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

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Study 1
Introduction

Independent study of nomenclature of alcohols and ethers

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
Introduction

Carbocation rearrangements
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

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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 CH3 C H C H H 1,2-hydride shift C CH2CH2CH2CH3 CH3 C H C H C CH2CH2CH2CH3 H H

CH2CH2CH2CH3

ALLOWED

CH2CH2CH2CH3

a secondary (2o) carbocation

a tertiary (3o) carbocation

H CH3 C H C H

CH3 1,2-metthyl shift C CH2CH2CH2CH3 CH3

H C H

CH3 C H C CH2CH2CH2CH3

CH2CH2CH2CH3

ALLOWED

CH2CH2CH2CH3

a secondary (2o) carbocation

a tertiary (3o) carbocation

H CH3 C H C H

CH3 1,2-butyl shift C CH2CH2CH2CH3 CH3

H C H

CH2CH2CH2CH3 C H C CH3

CH2CH2CH2CH3

ALLOWED

CH2CH2CH2CH3

a secondary (2o) carbocation

a tertiary (3o) carbocation

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.
H H C H C H H C CH2CH2CH2CH3

OW ED

H H C H C H

H C CH2CH2CH2CH3

1,2-hydride shift

a secondary (2o) carbocation

NO

CH2CH2CH2CH3

AL L

CH2CH2CH2CH3

a primary (1o) carbocation

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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 CH3 C H

H C

H C CH2CH2CH2CH3

OW ED

H CH3 C H

H C

H C CH2CH2CH2CH3

1,2-butyl shift

a secondary (2o) carbocation

NO

CH2CH2CH2CH3

(a type of 1,2-alkyl shift)

AL L

CH2CH2CH2CH3

a secondary (2o) carbocation

1,2-hydride shift

CH2CH2CH2CH3

NO T

AL

CH3

CH2CH2CH2CH3

LO

ED

H CH3 C H C H

H C CH2CH2CH2CH3

CH2CH2CH2CH3

a secondary (2o) carbocation

a secondary (2o) carbocation

Rule 4 Rules 2 and 3 are overridden whenever the carbocation rearrangement leads to a reduction in ring strain e.g.
H H b c d CH3 a secondary (2o) carbocation highly strained four-membered ring a e H 1,2-alkyl shift b (Cd migrates from Ca to Ce) c a e d H CH3 1,2-hydride shift b c a e d CH3 H H

ALLOWED

a secondary (2o) carbocation much less strained five-membered ring

ALLOWED

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Study 3
Introduction

Conversion of alcohols to alkyl halides (Route 1)

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 OH HX C C C H X

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)

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Overview of Route 1

OH

hydroxide is a poor leaving group

HCl, HBr, HI

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)

H R O H X water is a good leaving group

SN2 pathway, if alcohol is .

SN1 pathway, if alcohol is .

carbocation invoke appropriate rearrangements

Lets take a look at a few worked examples

HO HI

OH

HBr

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HCl

OH

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OH HBr C CH3 CH3

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MAKING CONNECTIONS
O HBr CH3OH CH3Br Mg in dry diethyl ether 1 CH3MgBr in diethyl ether 2. H3O+ no direct path CH3CH2CH2OH

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Study 4
Introduction

Conversion of alcohols to alkyl halides (Route 2)

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 OH PBr3, PCl3 or PI3 C and pyridine (as solvent and as proton scavenger) C C H X

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

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Overview of Route 2
R OH hydroxide is a poor leaving group 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

PX3 a phosphorus trihalide in pyridine (solvent and proton scavenger)

X R O P X X a halophosphite group which is a good leaving group

Reaction occurs if alcohol is X .

Reaction does not occur if alcohol is .

Lets take a look at a few worked examples

OH C CH3 CH3 PCl3, pyridine

PBr3, pyridine

OH

OH

PCl3, pyridine

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MAKING CONNECTIONS
OH PBr3, pyridine Br Li in dry hexane Li 1 O OH

in diethyl ether 2. H3O+

no direct path

Study 5
Introduction

Conversion of alcohols to alkyl sulfonate esters

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 OH C Cl O S O R1 pyridine C (as solvent and as proton scavenger) C H OSO2R'

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

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Overview of alkyl sulfonate ester formation

OH

hydroxide is a poor leaving group

O Cl S O in pyridine (solvent and proton scavenger) R1 a sulfonyl chloride

Types of 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

O R O S O an alkyl sulfonate ester R1 excellent leaving group (100 times better than chloride ion!!)

Typical sulfonyl chlorides (R1SO2Cl)

O CH3 S O para-toluenesulfonyl chloride (aka tosyl chloride) (aka TsCl) Cl CH3 O S O methanesulfonyl chloride (aka mesyl chloride) (MsCl) Cl CF3 O S O trifluoromethanesulfonyl chloride (aka triflyl chloride) (aka TfCl) Cl

Typical sulfonate esters (R1SO2OR)

O CH3 S O a para-toluenesulfonate ester (a tosylate) (aka ROTs) OR CH3

O S O a methanesulfonate ester (a mesylate) (aka ROMs) OR CF3

O S O a trifluoromethanesulfonate ester (a triflate) (aka ROTf) OR

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Lets take a look at a few worked examples

MsCl, pyridine OH

OH

TsCl (1 mole), pyridine

OH 1 mole

Alkyl sulfonate esters in synthesis

MAKING CONNECTIONS
CH3CH2OH MsCl, in pyridine CH3CH2OMs NaCN, DMSO, heat from CH 331 CH3CH2CN

no direct path

MAKING CONNECTIONS
CH3CH2OH TsCl, in pyridine CH3CH2OTs NaSCH3, DMSO, heat from CH 331 CH3CH2SCH3

no direct path

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Study 6
Introduction

Dehydration of alcohols
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?
H C OH H2SO4 (or H3PO4) C heat

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, state that the dehydration of a primary alcohol proceeds via the E2 pathway state that the dehydration* of a secondary alcohol proceeds via the E1 pathway state that the dehydration* of a tertiary alcohol proceeds via the E1 pathway give the organic product(s) that arise from the dehydration* of an alcohol explain why acid (either sulfuric acid or phosphoric acid) is required 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
a) b) c) d) e) f)

* carbocations involved, therefore one or more carbocation rearrangements may occur (following the rules in Study 2)

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Overview of alcohol dehydration

hydroxide is a poor leaving group

OH

H2SO4 (or H3PO4)

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)

H R O H OSO3H water is a good leaving group

E2 pathway, if alcohol is .

E1 pathway, if alcohol is .

carbocation invoke appropriate rearrangements

Conditions employed to effect the complete dehydration of an alcohol

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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.
Hhydrogenation = -28.0 kcal/mole Hhydrogenation = -26.9 kcal/mole

e.g.
Hhydrogenation = -28.0 kcal/mole Hhydrogenation = -26.5 kcal/mole

energy

energy

R H H

>
R R R H

>
R H

>
R H

>
H H

>
H H

tetrasubstituted alkenes most stable alkene

trisubstituted alkenes

disubstituted alkenes

disubstituted alkenes

monosubstituted alkenes

ethylene least stable alkene

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Lets take a look at a few worked examples

OH

H2SO4, heat

OH

H2SO4, heat

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OH H2SO4, heat

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Study 7
Introduction

Redox reactions in organic chemistry

This unit examines the method for determining whether an organic compound has been oxidized, reduced or neither, in a given reaction N/A

Bruice section(s)

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 Oxidation level = # CA bonds - # CH bonds - # CB bonds -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 Lets look at a few examples
Oxidation level of reactant a)
O

product

Net change in oxidation level

Reactant has been Oxidized Reduced Neither oxidized nor reduced Oxidized Reduced Neither oxidized nor reduced Oxidized Reduced Neither oxidized nor reduced

b)

c)

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Study 8
Introduction

Oxidation of alcohols
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?
O R C H

an aldehyde R CH2OH O a primary alcohol R C OH

a carboxylic acid

O R C a ketone R CH R a secondary alcohol R C R a ketone OH O R

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) b) c) d) e) f) g) h) i)

state that the treatment of methanol with aqueous chromic acid yields formic acid state that the treatment of a primary alcohol with aqueous chromic acid yields a carboxylic acid state that the treatment of a secondary alcohol with aqueous chromic acid yields a ketone state that the treatment of methanol with PCC in anhydrous dichloromethane (CH2Cl2) yields formaldehyde state that the treatment of a primary alcohol with PCC in anhydrous dichloromethane (CH2Cl2) yields an aldehyde state that the treatment of a secondary alcohol with PCC in anhydrous dichloromethane (CH2Cl2) yields a ketone give the various combinations of reagents that give aqueous chromic acid (aq H2CrO4) predict the organic product(s) that arise from the reaction between an alcohol and chromic acid predict the organic product(s) that arise from the reaction between an alcohol and PCC in anhydrous dichloromethane

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How to prepare aqueous chromic acid

Recipe #1 H2O Na2Cr2O7 sodium dichromate + H2SO4 sulfuric acid H2CrO4 chromic acid

Recipe #2 H2O CrO3 chromium trioxide + H2SO4 sulfuric acid H2CrO4 chromic acid

Lets take a look at a few worked examples

OH aqueous H2CrO4

OH

aqueous H2CrO4

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aqueous H2CrO4

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OH

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Cut off for the Midterm Exam

Study 9
Introduction

Substitution reactions of ethers

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 HX R 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, 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)

* carbocations may be involved, therefore one or more carbocation rearrangements may occur (following the rules in Study 2)

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An overview
alkoxides are poor leaving groups

OR

2 HX (HCl, HBr or HI)

H R O R X alcohols are good leaving groups

SN2 pathway, if the R group is .

SN1 pathway, if the R group is .

carbocation invoke appropriate rearrangements

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Lets take a look at a few examples

O HI

O HBr

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Study 10
Introduction

Substitution reactions of epoxides under acidic conditions

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, 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)

Lets take a look at a few examples

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Study 11
Introduction

Substitution reactions of epoxides under neutral or basic conditions

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, 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
a)

Lets take a look at a few examples i)

formed in equal amounts (as a racemic mixture) H O a b H 1. NaN3 2. H3O+ Na+ as counter ion N3 as nucleophile N3 H OH

OH H Ca is a secondary center and thus suited to SN2 attack Cb is a secondary center and thus suited to SN2 attack

N3 Ca and Cb are equally likely to be attacked. This leads to equal amounts of the products shown.

Reaction mechanism for the formation of first product Na+ N3 The nucleophile attacks from the side opposite the epoxide ring (note the inversion of configuration at Ca) OH b H H

H O a b H

N3

H
+ O Na

N3 H3O+

a b

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ii)
O a b Na+ as counter ion OCH3 as nucleophile 1. NaOCH3 2. H3O+ OH Ca is a tertiary center and thus not suited to SN2 attack Cb is a primary center and thus suited to SN2 attack CH2OCH3 sole organic product product arises solely from attack at Cb

Reaction mechanism

O a b a

Na+

OH H3O+ a CH2OCH3 b

CH2OCH3 b

Na+

OCH3

iii)
Li+ as counter ion CH3 as nucleophile H CH3Li, dry ether O b 2. H3O+ CH2CH3 major organic product Reaction mechanism for the formation of first product H a O b
+ CH3 Li

H a

Ca is a secondary center and thus suited to SN2 attack OH CH3 H 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 CH2OH minor organic product

H O a b CH2CH3 Li+

H3O+ a

H OH

b CH2CH3

Reaction mechanism for the formation of second product H a a O b

+ CH3 Li

CH3 H

H3O+ a

CH3 H

b CH2O

Li+

b CH2OH

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Study 12
Introduction

Crown ethers
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 Li

O Li

[12]-crown-4

Li bound in [12]-crown-4

For an interesting discussion of the link between nonactins ability to act like a crown ether and its antibiotic behavior please see Bruice page 440.

Study 13
Introduction

Thiols and sulfides

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

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The amino acid cysteine (shown below) contains a thiol

O H3N CH CH2 SH C OH

Thiols (pKa ~ 10) are stronger acids than alcohols (pka ~ 15) since thiolate ions are more stable than alkoxide ions.
NaH SH S Na

a thiol

a thiolate ion

Thiolate ions are good nucleophiles

CH3Br, S DMSO, heat a thiolate ion a sulfide SCH3

Sulfides Sulfides are also known as thioethers Sulfides are sulfur analogues of ethers Sulfides are good nucleophiles
CH2CH3 SCH3 a sulfide CH3CH2Br, DMSO, heat a sulfonium salt SCH3 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 2.18a 3.20a 2.20 3.22 10.5 11.5(a,b,c,f) 10.7 11.10 10.10 11.13 10.12(a,b) 11.14 Bruice 6th Bruice 7th 10.12c 11.15a 10.13b 11.15b 10.14 11.18 10.17 11.21 10.20 11.24 10.21 11.25 Bruice 6th Bruice 7th 10.33(all but g) 11.48(all but g) 10.38(a,b,c,d,e,f,g) 11.54(a,b,c,d,e,f,g) 10.48 11.69 10.52 11.72 10.55 11.75

Additional assigned questions

Solutions are available on Blackboard
1.

Deduce the structures of compounds A, B and C. Dont forget to use wedge/dash notation where appropriate.
HO OH 1 mole NaH (1 mole), DMF A BnBr (1 mole), DMF, heat B dry CH2Cl2 PCC C

Br

BnBr

2.

Deduce the structures of compound D and E. Dont forget to use wedge/dash notation where appropriate.
OH OH TsCl (1 mole), pyridine D HO H OCH3 (1 mole) NaCN, DMSO, heat E

3.

Deduce the structures of compounds F, G, and H. Dont forget to use wedge/dash notation where appropriate.

Li, hexane Br F

1. F, dry ether G 2. H3O+

PCC, dry CH2Cl2