1. Reactions of Alcohols, Amines, Ethers, and Epoxides
Essential Organic Chemistry
Paula Yurkanis Bruice
Chapter 10
Reactions of Alcohols, Amines,
Ethers, and Epoxides

2. 10.1 Nomenclature of Alcohols
Compounds in which a hydrogen is replaced by an OH group.
We distinguish three types:

3. Naming Alcohols
Common names are the name of alkyl group followed by the word “alcohol”

4. Naming 1. Longest carbon chain containing the alcohol.
2. OH suffix gets the lowest possible number.

5. Naming 3. Find also lowest possible number for other substituent.
4. For more than one substituent they are listed in alphabetical order.

9. 10.2 Substitution Reactions of Alcohols
Alcohols are not reactive in nucleophilic substitution
or elimination reactions since hydroxide is a strong base,
poor leaving group.
SN1
SN2
no reaction in
either case
strong
base
poor leaving
group

10. Substitution Reactions of Alcohols
The situation improves under acid conditions. We change the leaving group to water, a neutral group.
neutral
neutral

12. Figure: UN
Title:
Substitution Reactions of Various Alcohols
Caption:
Primary, secondary, and tertiary alcohols all undergo nucleophilic substitution in the presence of such acids as HCl, HBr, and HI to form alkyl halides.
Notes:
Secondary and tertiary alcohols undergo substitution by an SN1 mechanism with these hydrogen halides.

13. Figure: UN
Title:
Mechanism of an SN1 Reaction of an Alcohol
Caption:
The carbocation formed in this mechanism has two fates: either reaction with a nucleophile to produce a substitution product or to form an elimination product.
Notes:
Even if the elimination product forms it reacts with the excess acid to form the alkyl halide.

14. Figure: UN
Title:
Mechanism of an SN2 Reaction of an Alcohol
Caption:
The protonation of the alcohol by the acid is the rate-determining step and it is bimolecular.
Notes:
Primary alcohols undergo SN2 reactions with hydrogen halides.

18. 10.3 Elimination Reactions of Alcohols
Elimination of water, dehydration, is commonly obtained using sulfuric acid (H2SO4) as a catalyst.
The acid is mandatory to convert the poor leaving group OH– into a good leaving group H2O.

19. Elimination First step is protonation of the hydroxyl group.
Loss of water leads to a carbocation.

20. Figure: UN
Title:
Dehydration of an Alcohol
Caption:
Dehydration of an alcohol requires an acid catalyst and heat. The most common catalyst is sulfuric acid. This reaction proceeds by an E1 mechanism.
Notes:
An acid protonates the most basic atom (electron-rich) in a molecule. Secondary and tertiary alcohols undergo dehydration by an E1 mechanism.

21. Elimination
Second, a base removes a proton b to the carbocation center.
Notice that this reaction is an E1 reaction.
Rate-determining step is the formation of the carbocation.

22. Elimination
In case we have a choice between several b-hydrogens, the most stable alkene is formed preferentially.
84 % 16 %

23. Figure: 11-01
Title:
Reaction Coordinate Diagram for Dehydration of an Alcohol
Caption:
The reaction coordinate diagram for the dehydration of a protonated alcohol. The major product is the more substituted alkene because the transition state leading to its formation is more stable, allowing it to be formed more rapidly.
Notes:
The formation of the carbocation is the rate-determining step since it has the highest activation energy.

24. Elimination
As a result of the E1 mechanism, the ease of dehydration follows the order:
That directly reflects the stability of the
intermediate carbocations.

25. Figure: UN
Title:
Relative Ease of Dehydration
Caption:
A tertiary alcohol is more easily dehydrated than a secondary than is a primary. This is because of the stability of the carbocation intermediate that forms during the reaction.
Notes:
Remember that tertiary carbocations are easier to form than are secondary carbocations.

27. Elimination Primary alcohols undergo dehydration by an E2 pathway.
First, however, we generate the good leaving group.
The subsequent steps, removal of water and
deprotonation, take place simultaneously.

29. Figure: UN
Title:
Dehydration of a Secondary Alcohol
Caption:
The products obtained in this acid-catalyzed dehydration are the same as those obtained from the elimination of an alkyl halide. There is formation of the two stereoisomers E and Z, with the E isomer being the favored product.
Notes:
There is also some production of 1-butene.

32. 10.4 Oxidation of Alcohols Dehydrogenation (oxidation) is possible for
1o and 2o leading to aldehydes and ketones, respectively.
aldehyde
ketone

33. Oxidation of Alcohols Aldehydes can be further oxidized to acids.

34. Oxidation of Alcohols
Typical oxidizing agents are chromic acid (H2CrO4)
or pyridinium chlorochromate (PCC).
chromic acid
PCC

35. Examples
cyclopentanol
cyclopentanone
butanol
butanal
butanoic acid

36. Examples PCC is a more selective oxidizing agent.
butanol
butanal
PCC is a more selective oxidizing agent.
Oxidation can be stopped at the aldehyde level.

38. 10.5 Reaction of Amines Amines are less reactive than alcohols.
This can be evaluated by inspection of the pKa values of the leaving group.
Protonation of the amine improves the
situation only slightly.

39. Amines
Amines are the most common organic bases.

41. 10.6 Nomenclature of Ethers
Common Name:
Name of alkyl substituents followed by “ether”

42. Nomenclature of Ethers
IUPAC
Parent alkyl compound with RO substituent. “-yl” is then replaced by “oxy”

44. 10.7 Substitution Reactions of Ethers
The behavior of ethers is comparable to alcohols.
pKa of the leaving group is comparable.
Activation by acid allows substitution.

45. Figure: UN
Title:
General Substitution Reaction of Ether
Caption:
Ethers can be activated by protonation. They can undergo substitution with HBr or HI but the reaction must be heated.
Notes:
This is the same as with alcohols. The OR group is not a good leaving group until it is protonated.

46. Substitution of Ethers
The mechanism involves first a protonation step.
The subsequent steps are determined by the stability of the intermediates.
Stable carbocation  SN1
Unstable carbocation  SN2

47. Substitution of Ethers
Examples
attack of nucleophile
stable carbocation

48. Figure: UN
Title:
Mechanism of Substitution Reaction of Ether
Caption:
The first step is the protonation of the ether by the acid. This makes a better leaving group and a carbocation can be formed.
Notes:
This mechanism is an SN1 mechanism since a stable carbocation is formed.

49. Substitution of Ethers
Primary carbocations are unstable;
thus, reaction proceeds via SN2.
Reaction takes place on the less hindered of the
two alkyl groups.

50. Figure: UN
Title:
Mechanism of a SN2 Reaction of an Ether
Caption:
If the departing group does not form a stable carbocation the leaving group cannot leave. The mechanism becomes SN2.
Notes:
Ethers are frequently used as solvents since the only thing they react with are acids.

51. Ethers Only hydrogen halides react with ethers
Ethers commonly used as solvents
Often used solvents are:

52. Figure: UN.T1
Title:
Table Ethers Used as Solvents
Caption:
Ethers are frequently used as solvents since the only thing they react with are acids.
Notes:
Listed are common ethers such as diethyl ether, THF, DME, and MTBE.