A Preview of Carbonyl Compounds

Unit Preview

So far, in our survey of the oxygen-containing organic compounds, we have studied the chemistry of ethers and alcohols. Now we turn our attention to a much larger group of compounds—those containing a carbonyl group: C=O The variety of carbonyl compounds is so wide, and their chemistry is so extensive, that we shall need the next five units to discuss them thoroughly. One advantage of Organic Chemistry, 8th ed., as a textbook is that the author has divided up his discussion of carbonyl compounds so that this large amount of factual material can be studied in small, readily digestible blocks. The purpose of this unit is to provide a general outline of what is to follow in the next five units: the various types of carbonyl compounds are introduced, the nature of the carbonyl group is explained, and the four most common mechanisms by which carbonyl groups react are described in general terms.

Unit Objectives

When you have completed this unit, you should be able to
1. fulfill all of the detailed objectives listed under each individual section.
2. identify the various types of carbonyl compounds.
3. write the mechanism of each of the four general types of reactions discussed in the unit.
4. define, and use in context, the key terms introduced in this unit.

Introduction

Objectives

After completing this section, you should be able to give examples of the wide variety of biologically important, pharmaceutical and industrial compounds that contain one or more carbonyl groups.

Key Terms

carbonyl group (see the “Study Notes,” below) Study Notes A “carbonyl group” consists of an sp2-hybridized carbon atom that is joined to an oxygen atom by a double bond.

I Kinds of Carbonyl Compounds

Objectives

After completing this section, you should be able to
1. identify the following types of compounds as containing carbonyl groups: aldehydes, ketones, carboxylic acids, acid chlorides, acid anhydrides, esters, lactones, amides and lactams.
2. identify the important difference between aldehydes and ketones, and the other types of compounds listed under Objective 1, above.

Key Terms

acyl fragment or acyl group (see the “Study Notes,” below)

Study Notes

The idea of an “acyl group” is not really new. Recall that in Unit 16 of Chemistry 350 we discussed the introduction of acyl groups into benzene rings by means of the Friedel-Crafts acylation reaction. Note the use of the word “moiety” as an alternative to “group” or “fragment.” Study the different types of carbonyl compounds listed in Table 1 (Organic Chemistry, 8th ed., page 713) so that you can immediately recognize to which type a given compound belongs. Note that these compounds can be divided into two broad categories: aldehydes and ketones, and carboxylic acids and their derivatives. Look for differences between these two categories, as well as for differences and similarities among the individual compound types.

II Nature of the Carbonyl Group

Objectives

After completing this section, you should be able to describe the electronic structure, polarity, and geometry of the carbonyl group.

Study Notes

The most important point for you to keep in mind as you study the reactions of carbonyl compounds is the way in which the carbonyl group is polarized:

III General Reactions of Carbonyl Compounds

Objectives

After completing this section, you should be able to
1. list the four general reaction mechanisms that dominate the chemistry of carbonyl compounds.
2. discuss nucleophilic addition reactions of aldehydes and ketones (Chapter 19).
a. write a general mechanism for nucleophilic addition to a carbonyl compound.
b. write a detailed mechanism for the addition of a given nucleophile (e.g., a Grignard reagent) to an aldehyde or ketone.
c. write a general mechanism to illustrate reactions in which the addition of a nucleophile to the carbonyl group of an aldehyde or
ketone is followed by the elimination of water.
d. write the detailed mechanism for a reaction in which the addition of a given nucleophile to the carbonyl group of an aldehyde or ketone is followed by the elimination of water.
3. discuss nucleophilic acyl substitution reactions of carboxylic acid derivatives (Chapter 21).
a. write a general mechanism to illustrate nucleophilic acyl substitution reactions.
b. write a detailed mechanism for the reaction of a given carbonyl-containing compound with a given nucleophile through a
nucleophilic acyl substitution.
4. discuss alpha substitution reactions (Chapter 22).
a. write a general mechanism to illustrate alpha-substitution of a carbonyl compound through the formation of an enol or enolate
anion.
b. explain the stability and ease of formation of enolate anions.
c. write the detailed mechanism for the formation of an alpha-substituted carbonyl compound from the overall reaction of a
carbonyl compound with a primary alkyl halide.
5. discuss carbonyl condensation reactions (Chapter 23). a. write a general mechanism to illustrate the condensation reaction that can occur between two molecules of a carbonyl compound; for example, the reaction of two molecules of acetaldehyde to form one molecule of aldol.

Key Terms

Note: All of these terms are defined in the “Study Notes,” below.

aldol reaction
alkylation
alpha substitution
carbonyl condensation
enol
enolate anion
nucleophilic acyl substitution
nucleophilic addition reaction

Study Notes

A “nucleophilic addition reaction” (of a carbonyl compound) involves the initial attack of a nucleophile on the slightly positive carbonyl-carbon atom to form a tetrahedral intermediate. Notice that of the two routes shown in Figure 2 (Organic Chemistry, 8th ed.,
page 715), only the first one is a true addition reaction; the second one gives overall substitution, and might better be described as an addition-elimination. This latter point is made more apparent in the mechanism of imine formation shown in Figure 3 on page 716. In a “nucleophilic acyl substitution reaction,” a nucleophile attacks the carbonyl carbon of a carboxylic acid derivative

and initially produces a tetrahedral intermediate. The intermediate then reacts by expelling the leaving group, X, thereby forming a new carboxylic acid derivative. In an “alpha substitution reaction” of a carbonyl compound, one of the hydrogen atoms attached to a carbon atom adjacent to the carbonyl group is removed and replaced by some other group. Alpha substitution reactions of carbonyl compounds involve the “enol” form of the compound. Keto-enol tautomerism was briefly introduced in Section 9.4, page 319 of the textbook. Review this section if necessary.

As you can see from the above diagram, the enol form has a hydroxyl group attached to one of the sp2-hybridized carbon atoms of a carbon-carbon double bond. Removal of the proton from the hydroxyl group produces a resonance-stabilized “enolate anion”:

A “carbonyl condensation reaction” is one in which two carbonylcontaining molecules condense together (i.e., join together), often with the elimination of water. The reaction involves the formation of an enolate anion from one carbonyl-containing molecule, followed by the subsequent nucleophilic attack by this enolate anion on the carbonyl carbon atom of the second molecule.

IV Summary

The purpose of this unit has been to introduce you to the various types of carbonyl compounds, and to give you a general overview of four different reaction mechanisms that dominate carbonyl-group chemistry.

Exercises

Do Problems 2 and 3 on page 721 of Organic Chemistry, 8th ed.