23.6 Intramolecular Aldol Reactions

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Objectives

After completing this section, you should be able to

write an equation to illustrate an intramolecular aldol reaction.
identify the product formed when a given dicarbonyl compound undergoes an intramolecular aldol condensation.
identify the dicarbonyl compound which, when treated with a suitable base, could be used to prepare a given cyclic enone by an intramolecular aldol condensation.

Study Notes

“Intramolecular ” means “within the same molecule.” You have already seen some examples of intramolecular reactions in previous chapters. Another term for intramolecular aldol reaction is “internal aldol reaction.”

Intramolecular aldol reaction

Molecules which contain two carbonyl functionalities have the possibility of forming a ring through an intramolecular aldol reaction. In most cases two sets of \(\alpha\) hydrogens need to be considered. As with most ring forming reaction five and six membered rings are preferred (less ring strain).

As with other aldol reaction the addition of heat causes an aldol condensation to occur.

Worked Example 23.6.1

Please draw the expected product of an intramolecular aldol condensation with the following molecule:

Answer

Analysis: 6-Oxoheptanal has three unique sets of alpha-hydrogens which could be deprotonated to form an enolate. Selecting the correct set involves analyzing the carbonyl reactivity’s along with the possible ring sizes of the products.

Solution: Once the preferred alpha-hydrogens are determined go through the steps discussed in the previous sections to determine the aldol condensation product. Remember to form the aldol intermediate first.

Exercises

Exercise 23.6.1

Briefly explain why the molecule, 2,4-pentanedione, when reacted with a base would mostly likely not produce an intramolecular aldol condensation product.

Answer

2,4-Pentanedione like other 1,3-Diketones have particularly acidic alpha-hydrogens between the two carbonyl. When base is applied these will be the first to deprotonate and form an enolate. For an intramolecular aldol condensation to occur an alpha-hydrogen one of the methyl groups would have to be removed which would be difficult.

Exercise 23.6.2

Draw the product of the following aldol condensation:

Answer

Contributors and Attributions

Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)
Prof. Steven Farmer (Sonoma State University)