Class Summary and Notes from 10/17/00

Class Summary and Notes from 10/17/00 - CHEM3312

Topic: Alkylations of Carbonyl Compounds at the alpha position

Summary

During the previous class we discussed that the hydrogens at the alpha position of carbonyl compounds are acidic and can be removed with strong bases. These alpha positions then are nucleophilic, and react with electrophiles. (We discussed their reaction with Br₂ in the last class) Today's class focuses on the use of carbon electrophiles in order to add alkyl groups to the alpha position of carbonyl compounds. Following is the general scheme for such reactions.

Electrophilic alkyl groups that can be used in this reaction were the topic of the first in-class problem. Section 22.8 discusses reactions that use alkyl halides as the electrophiles. Chapter 23 focuses on reactions that use carbonyl groups or a,b-unsaturated carbonyl compounds as the electrophile. Two special starting materials were introduced for use as the enolate component in an a-alkylation reaction. These two compounds are acetoacetic ester and malonic ester.

These starting materials can be used as enolates in the following manner:

A summary of the previous reactions without the mechanism:

Acetoacetic ester is generally useful for preparing substituted acetones, whereas malonic ester is generally useful for preparing substituted acetic acids.

Problems Discussed In Class

What types of carbon electrophiles have we used in previous reactions?

Results of Class Discussion

Alkyl halides (R-Br)
Carbonyl groups (C=O)
a,b-unsaturated carbonyl compounds

How can 2-hexanone be prepared using an enolate and a compound with an electrophilic carbon?

Results of Class Discussion

Note: See the example of the acetoacetic ester synthesis above for an alternative preparation of this same compound. The advantage to using acetoacetic ester is the ability to use a milder base.

Since NaOH does not completely convert acetone to its enolate, but rather results in a minor conversion to enolate (~0.1%), is there any reaction that acetone and its enolate will do?

Results of Class Discussion

Note: This reaction is called the Aldol reaction, and the equilibrium tends to favor starting material rather than product unless unhindered aldehydes are used. So the reaction in the example above does not occur extensively.

What is the aldol product produced when treating butanal with NaOH?

Results of Class Discussion

2-ethyl-3-hydroxyhexanal (and this product IS favored in the equilibrium as the starting material is an aldehyde without many substituents on the a carbon)

The Claisen reaction was introduced as the aldol-type of reaction for esters. The difference between this reaction and the aldol, is the same difference introduced for nucleophilic attack on aldehydes vs. carboxylic acid derivatives (including esters). The carboxylic acid derivatives have substituents on the carbonyl group that can serve as leaving groups. Following is the mechanism of a Claisen reaction, note the point of difference from the aldol.

Special Notes

Last modified 10/19/00

Dr. Abby Parrill
Department of Chemistry
University of Memphis

These pages may be downloaded and linked from other pages freely for academic and educational purposes. Questions, problems, and errors should be sent to aparrill@memphis.edu.