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22.0: Chapter Objectives and Introduction to Carbonyl Alpha-Substitution Reactions

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  • When you have completed Chapter 22, you should be able to

    1. fulfill all of the detailed objectives listed under each individual section.
    2. design multi‑step syntheses in which the reactions introduced in this unit are used in conjunction with any of the reactions described in previous units.
    3. solve road‑map problems that require a knowledge of carbonyl alpha‑substitution reactions.
    4. define, and use in context, the key terms introduced.

    After completing this section, you should be able to write a general mechanism for an alpha‑substitution reaction of a carbonyl compound.

    Key Terms

    Make certain that you can define, and use in context, the key terms below.

    • alpha (α) position
    • alpha‑substitution reaction
    Study Notes

    An “alpha‑substitution reaction” of a carbonyl compound is a reaction in which one of the hydrogen atoms on the carbon adjacent to the carbonyl group is substituted by some other atom or group. Attack by the electrophile (E+) can occur on the enol or enolate intermediate.

    alpha substitution reaction through enol and enolate intermdediates

    There are four common types of reactions involving molecules containing a carbonyl bond. The first two, nucleophilic addition and nucleophilic acyl substitution have been discussed in previous chapters.

    Nucleophilic addition occurs due to the electrophilic nature of the carbonyl carbon. After addition of a nucleophile, the carbonyl becomes a tetrahedral alkoxide intermediate which is usually protonated to become an -OH group.

    Nucleophilic Addition to a Carbonyl

    Nucleophilic acyl substitution is similar in that a tetrahedral alkoxide intermediate is formed after nucleophilic addition to the carbonyl. However, subsequent removal of the leaving group allows for the C=O (carbonyl) bond to reform. Overall, there is a substitution of the leaving group with the incoming nucleophile.


    Nucleophilic Acyl Substitution Involving a CarbonylEdit section

    Reactions at The Alpha Carbon

    The remaining common carbonyl reaction types are α substitutions and carbonyl condensations. Both utilize the special properties of carbons directly adjacent to carbonyls which are called α carbons. These reactions, which can be regarded as the backbone of much synthetic organic chemistry, usually result in the replacement of a hydrogen attached to an α carbon with some type of electrophile. These reactions involve two new neucleophilic species called the enol and the enolate.


    This chapter will focus on α substitutions reactions. Although there are many carbonyl containing functional groups, the initial investigation in this chapter will focus on α substitutions reactions with aldehydes and ketones. Important examples considered in this chapter include α-halogenation and α-alkylation.

    Contributors and Attributions

    Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)

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