ORGANIC CHEMISTRY II (OCH221T)

CHEMICAL ENGINEERING CLASS 2017B

Prescribed textbook: Fundamental of Organic Chemistry, 7th ed (John McMurry)

Alternative recommended textbook: Organic chemistry, 3rd ed (JG Smith)

Dr Matshawe Tukulula: Room 3-626D (TukululaM@tut.ac.za)
SYLLABUS THEME 10: ALDEHYDES AND KETONES
 STUDY UNIT 10.1: STRUCTURE AND NOMENCLATURE

STUDY UNIT THEME 10.1.1: STRUCTURE, NOMENCLATURE AND

PROPERTIES

 STUDY UNIT 10.2: SYNTHESIS OF ALDEHYDES AND KETONES

 STUDY UNIT 10.3: REACTIONS OF ALDEHYDES AND KETONES

STUDY UNIT 10.1: STRUCTURE AND NOMENCLATURE
 STUDY UNIT THEME 10.1.1: STRUCTURE, NOMENCLATURE AND
PROPERTIES

 SPECIFIC OUTCOMES

- Draw an orbital picture of the carbonyl group

- Discuss the differences in the reactivity of carbonyl compounds
- Use IUPAC system to name aldehydes and ketones
- Distinguish between tautomers and isomers (Already covered previously,
remember keto-enol-tautomerism?)
INTRODUCTION TO ALDEHYDES AND KETONES
 In nature aldehydes and ketones are found in living organisms:

 Aldehyde play a major role in a number of important metabolic reactions

 Ketones regulates important biological process such as fat regulations,

proteins and carbohydrate metabolism

 In chemical industry, simple aldehydes and ketones are used as solvents

and starting material in reactions

 Aldehydes and ketones are key intermediates in synthesis of pharmaceuticals

INTRODUCTION TO ALDEHYDES AND KETONES
 Aldehydes and ketones contain a carbonyl group (-C=O)

 An aldehyde contains at least one H atom bonded to the carbonyl C atom

 A ketone has two alkyl or aryl groups bonded to the carbonyl C atom
INTRODUCTION TO ALDEHYDES AND KETONES
 Two structural features determine the chemistry and properties of
aldehydes and ketone:

(i) C=O group is sp2-hybridized and trigonal planar, thus relatively uncrowded

(ii) Electronegative O atom polarizes the C=O group, making the C atom E+

 As a result aldehydes and ketones react with Nu:

INTRODUCTION TO ALDEHYDES AND KETONES
 The relative reactivity of the C=O is determined by the number of the R
groups bonded to it:

 As the number of R groups increases, reactivity of C=O decreases

WORKED EXAMPLE ON CARBONYL COMPOUNDS REACTIVITY
 Rank the following compounds in order of increasing reactivity towards
nucleophilic attack:

-Answer:
As the R groups increases on the C=O, reactivity decreases: In A there are 3-
R groups, B two R groups and C four R groups. Thus, B will be most reactive,
followed by A and then C:
INTRODUCTION TO ALDEHYDES AND KETONES
 As mentioned, the C atom of the C=O group is sp2-hybridized, thus they are
similar to the C=C of alkenes:

 The C=O bond is highly polarised due to electronegativity difference:

NAMING OF ALDEHYDES: IUPAC SYSTEM
 Aldehydes are named by replacing the terminal –e of the corresponding
alkane name with –al:

 The parent chain must contain the –CHO group, and numbering begins at
the –CHO carbon, which is always C1:
NAMING OF ALDEHYDES: IUPAC SYSTEM
 Complex aldehydes in which –CHO group is attached to a ring, the suffix –
carbaldehyde is used:

 Common names for some aldehydes:

NAMING OF KETONES: IUPAC SYSTEM
 Ketones are named by replacing the terminal –e of the corresponding
alkane name with –one:

 The parent chain must also contain the ketone group, and numbering
begins at the end nearer to the C=O group:

 Some common names:

NAMING OF ALDEHYDES AND KETONES: WHAT HAPPENS WHEN
THEY ARE A SUBSTITUENT?
 When –COR group is used as a substituent, the general terms Acyl is used:

 When the doubly-bonded O atom is considered a substituents, the prefix-

oxo is used:
NAMING OF ALDEHYDES AND KETONES: ADDITIONAL
NOMENCLANTURE FACTS
 Compounds containing both a C=C and aldehyde are named as enals:

 Compounds containing both a C=C and ketone are named as enones:

WORKED EXAMPLE ON CARBONYL COMPOUNDS REACTIVITY
 Give the IUPAC Name for each of the following compounds:

-Answer:
SUMMARY ON STRUCTURE AND NOMENCLATURE
 We introduced both aldehydes and ketones, including their importance
both in nature and in industry.

 We looked at structures of both, including reactivity of the C=O group and

its hybridization.
- C=O and C=C are both sp2-hybridized and they are trigonal planar (bond
angle of 120o)

 We looked at naming of both groups and some of the common names and
naming of mixed functional groups.
RECAP ON SPECIFIC OUTCOMES
 Would you now be able to:

- Draw an orbital picture of the carbonyl group?

- Discuss the differences in the reactivity of carbonyl compounds?

- Use IUPAC system to name aldehydes and ketones?

- Distinguish between tautomers and isomers?

STUDY UNIT 10.2: SYNTHESIS OF ALDEHYDES AND KETONES

 SPECIFIC OUTCOMES

- Propose methods to prepare aldehydes from other functional groups

- Propose methods to prepare ketones from other functional groups

SYNTHESIS OF ALDEHYDES AND KETONES
 We already seen the synthesis of aldehydes and ketones from Theme 8 via the
oxidation of R-OH:
- 1o R-OH are oxidized into aldehydes using oxidising agents:

- 2o R-OH are oxidized into ketones:

SYNTHESIS OF ALDEHYDES AND KETONES
 Aldehydes are synthesized also from hydroboration of terminal alkynes (anti-
Markovnikov) in Theme 4 (remember?):

 Ketones are also synthesized from hydroboration of internal alkynes in Theme

4 (remember?):
SYNTHESIS OF ALDEHYDES AND KETONES
 Ketone can also synthesized from hydration of alkynes (Markovnikov) in
Theme 4 (remember?):

 Ketone can also synthesized from KMnO4 facilitated cleavage of alkene in

Theme 3 (remember?):
SYNTHESIS OF ALDEHYDES AND KETONES
 Both aldehydes and ketones can also be synthesized from the ozonolysis of
alkenes in Theme 3 (remember?):

 Ketone are also synthesized from Friedel-Craft acylation in Theme 5

(remember?):
SUMMARY ON THE SYNTHESIS OF ALDEHYDES AND KETONES
 In previous themes, we looked at various ways of synthesizing aldehydes
and ketones:
- In Theme 8, we saw that both can be synthesized from oxidation of R-OH.

- In Theme 4, both can be synthesized from hydroboration of alkynes and in

same theme, ketone were synthesized from hydration of alkynes.

- Ketone can also be synthesized from KMnO4 facilitated cleavage of C=C

(Theme 3) and via Friedel-Craft acylation (Theme 5).

- Both can also be synthesized from ozonolysis of C=C (Theme 3).

RECAP ON SPECIFIC OUTCOMES OF SYNTHESIS OF ALDEHYDES
AND KETONES

 By now, you should be able to use all previously studied reactions to:

- Propose methods to prepare aldehydes from other functional groups

- Propose methods to prepare ketones from other functional groups

STUDY UNIT 10.3: REACTIONS OF ALDEHYDES AND KETONES

 SPECIFIC OUTCOMES

- Predict products from reactions of aldehydes and ketones

- Use simple reactions of aldehydes and ketones (synthesis and

transformation) as part of multi-step syntheses of more elaborate
molecules

- Apply protecting group strategies in the use of the reactions of aldehydes

and ketones in multi-step syntheses.
REACTIONS OF ALDEHYDES AND KETONES: OXIDATION OF
ALDEHYDES
 Aldehydes are easily oxidized to yield carboxylic acids due to the presence
of CHO acidic proton that can be removed during oxidation.

- Ketones are unreactive towards oxidation, due to lack of an acidic proton.

- CrO3 in aqueous acid is the commonly used oxidizing agent for this reaction:
REACTIONS OF ALDEHYDES AND KETONES: OXIDATION OF
ALDEHYDES
 Oxidation by CrO3 occurs via intermediate 1,1-diols (hydrates/germinal
diols), formed by reversible addition of H2O to the C=O:

- Hydrates reacts similar to 1o or 2o R-OH and is rapidly oxidized:

 Silver oxide, Ag2O, in ammonium hydroxide (Tollen’s reagent) also oxidizes

aldehydes to CO2H efficiently:
WORKED EXAMPLE ON OXIDATION OF ALDEHYDES
 Predict the products of the reaction of the following substances with CrO3
in aqueous acid:

-Answer:
This is an oxidation type of a reaction. Among the C=O compounds, only the
aldehyde is able to be oxidized into CO2H: Thus, (a) and (b) are aldehydes
and would be oxidized but (c) is ketone and no reaction will take place:
REACTIONS OF ALDEHYDES AND KETONES: NUCLEOPHILIC
ADDITION REACTIONS
 These are the most common reactions of aldehydes and ketones:

- They occur both in acidic and basic conditions:

- Nu: adds to the electrophilic C atom of the C=O to form an alkoxide ion
which is then neutralised by addition of an acid:
REACTIONS OF ALDEHYDES AND KETONES: NUCLEOPHILIC
ADDITION OF WATER: HYDRATE FORMATION
 Aldehydes and ketones undergo nucleophilic addition reaction with H2O to
form germinal diols (not as an intermediate but product!):

 Increasing number of R groups decreases the amount of germinal diols:

REACTIONS OF ALDEHYDES AND KETONES: NUCLEOPHILIC
ADDITION OF WATER: HYDRATE FORMATION
 Base-catalyzed addition of H2O takes place rapidly because OH is a better
nucleophile than pure water:

 Acid-catalyzed addition of H2O occurs via the following mechanism:

WORKED EXAMPLE ON NUCLEOPHILIC ADDITION OF WATER
 What product would you expect from nucleophilic addition of aqueous
hydroxide ion to acetaldehyde?
-Answer:
First draw the structure so that you can visualize the reaction, noting that
acetaldehyde is ethanal:

-OH is a nucleophile and basic, thus this must be a base-catalyzed nucleophilic

addition reaction:
REACTIONS OF ALDEHYDES AND KETONES: NUCLEOPHILIC
ADDITION OF HYDRIDE AND GRIGNARD REAGENTS
 In Theme 8, we saw that C=O can be reduced to R-OH by the addition of a
reducing agent:

 What is the mechanism of this reaction?

REACTIONS OF ALDEHYDES AND KETONES: NUCLEOPHILIC
ADDITION OF HYDRIDE AND GRIGNARD REAGENTS
 More detailed mechanism for hydride addition:
REACTIONS OF ALDEHYDES AND KETONES: NUCLEOPHILIC
ADDITION OF HYDRIDE AND GRIGNARD REAGENTS
 In Theme 8, we also saw that C=O can be reduced to R-OH by Grignard
reagent:

 What is the mechanism of this reaction?

REACTIONS OF ALDEHYDES AND KETONES: NUCLEOPHILIC
ADDITION OF R-OH: ACETAL FORMATION
 Acetal formation involves acid-catalysed nucleophilic addition of an R-OH
to the C=O group.

 The initial nucleophilic addition step yields a hydroxyl ether called

hemiacetal, which reacts further with the 2nd R-OH to give an acetal.

- Reactions are reversible and acetal can be cleaved by an excess acid later:
REACTIONS OF ALDEHYDES AND KETONES: NUCLEOPHILIC
ADDITION OF R-OH: MECHANISM OF ACETAL FORMATION
REACTIONS OF ALDEHYDES AND KETONES: NUCLEOPHILIC
ADDITION OF R-OH: ACETAL AS PROTECTING GROUPS
 Acetal are valuable because they can serve as protecting groups for both
aldehydes and ketones. BUT how do they do that?

Acetals are valuable due to this

protecting ability
WORKED EXAMPLE ON ACETAL FORMATION REACTION
(a) Predict the product(s) of an acid-catalyzed reaction of 2-
methylcyclopentanone with methanol
-Answer:
A ketone reacts with an alcohol in the presence of an acid to yield an acetal.
To predict the product(s), replace the O atom of ketone with two OCH3 from
alcohol:

(b) Show how you might carry out the following transformation?

-Answer
WORKED EXAMPLE ON ACETAL FORMATION REACTION
(b) Show how you might carry out the following transformation?

-Answer
Looking closely on the product, one notices that there was selective
reduction of the ester to OH and addition of 2 x –CH3 group. Thus, there
must have been some protection step of the ketone C=O and use of Grignard
(remember Theme 8?):
REACTIONS OF ALDEHYDES AND KETONES: NUCLEOPHILIC
ADDITION REACTION: IMINE FORMATION
 Ammonia (NH3) and 1o R-NH2 add to aldehydes and ketones to yield
imines:
- Imines are compounds that have C=N bond:

 Occurs by addition of R-NH2 to the C=O group, followed by loss of H2O

from the intermediate amino alcohol:
REACTIONS OF ALDEHYDES AND KETONES: NUCLEOPHILIC
ADDITION REACTION: IMINE FORMATION
 Imines are NB intermediates in numerous biological pathways such as in
the synthesis and degradation of amino acids in the body:

 Biological degradation of alanine:

WORKED EXAMPLE ON IMINE FORMATION REACTION
 What product would you expect from a reaction of butan-2-one with
hydroxylamine, NH2OH?

-Answer:
First, always draw the structures so that you can visualize the reactions:

When a C=O compound reacts with an amine, the reaction yields an imine
products:
REACTIONS OF α,β-UNSATURATED ALDEHYDES AND KETONES:
CONJUGATED NUCLEOPHILIC ADDITION REACTIONS
 So far we have looked at only nucleophiles that add to the C=O directly
(termed 1,2-addition reactions):

 What happens when a nucleophile reacts with α,β-unsaturated carbonyl

compound?
REACTIONS OF α,β-UNSATURATED ALDEHYDES AND KETONES:
CONJUGATED NUCLEOPHILIC ADDITION REACTIONS
 Conjugate addition occurs due to the electronegative O atom of the α,β-
unsaturated carbonyl compound that withdraws e- from the β-C atom:

- e- withdrawal of makes the β-C atom more e- poor and more electrophilic
than a typical C=C bond:

 Reactions more common in many biological pathways such as food

metabolism:
WORKED EXAMPLE ON α,β-UNSATURATED CONJUGATE ADDITION
REACTION
 The following was prepared by a conjugated addition reaction between an
α,β-unsaturated ketone and an alcohol. Identify the two reactants.

-Answer:
Looking closely at the product, the cyclic part must have contained an α,β-
unsaturated system and the nucleophile must have been the alkoxide. Thus,
the two reactants are as follows:
SUMMARY ON THE SYNTHESIS OF ALDEHYDES AND KETONES
 We looked at the oxidation of aldehydes to CO2H by CrO3 and by
Ag2O/NH4OH.

 We looked at formation of 1,1-diols (germinal diols/hydrates) formed

from nucleophilic addition of water to C=O:
- Base and acid catalyzed addition of water.

 We revisited hydride and Grignard reduction of C=O, 1st seen in Theme 8.

 We looked at acetal formation and use of acetals as protecting groups.

SUMMARY ON THE SYNTHESIS OF ALDEHYDES AND KETONES
 We looked at the formation of imines from reaction of C=O with 1o R-NH2
or NH3:

- We also looked at an important biological process that involves imines (i.e.

synthesis and degradation of amino acids)

 We looked at α,β-unsaturated C=O compound’s 1,4 addition reactions with

nucleophiles.

- We also looked at an important biological process involves α,β-unsaturated

compounds (i.e citric acid cycle food metabolism)
RECAP ON SPECIFIC OUTCOMES OF REACTIONS OF ALDEHYDES
AND KETONES

 Would you now be in a position to:

- Predict products from reactions of aldehydes and ketones?

- Use simple reactions of aldehydes and ketones (synthesis and

transformation) as part of multi-step syntheses of more elaborate
molecules?

- Apply protecting group strategies in the use of the reactions of aldehydes

and ketones in multi-step syntheses?
THEME TEN (10) IS DONE AND DUSTED 