MCAT Organic Chemistry Review

Aldehydes and Ketones I: Electrophilicity and Oxidation—Reduction

Conclusion

In this chapter, we have examined the properties of aldehydes and ketones. Specifically, we have taken a look at the reactivity of the carbonyl carbon in nucleophilic addition reactions and examined how aldehydes and ketones can be oxidized and reduced. Carbonyls are common reaction sites in many biosynthetic processes, which helps explain their importance on the MCAT.

In the following chapter, we will continue our exploration of aldehydes and ketones by looking the chemistry of enolates, which are nucleophilic carbonyl-containing compounds.

Concept Summary

Description and Properties

·        Aldehydes are terminal functional groups containing a carbonyl bound to at least one hydrogen. In nomenclature, they use the suffix –al and the prefix oxo–. In rings, they are indicated by the suffix –carbaldehyde.

·        Ketones are internal functional groups containing a carbonyl bound to two alkyl chains. In nomenclature, they use the suffix –one and the prefix oxo– or keto–.

·        The reactivity of a carbonyl (C=O) is dictated by the polarity of the double bond. The carbon has a partial positive charge and is therefore electrophilic.

·        Carbonyl-containing compounds have higher boiling points than equivalent alkanes because of dipole interactions. Alcohols have higher boiling points than carbonyls because of hydrogen bonding.

·        Aldehydes and ketones are commonly produced by oxidation of primary and secondary alcohols, respectively.

o   Weaker oxidizing agents like pyridinium chlorochromate (PCC) must be used for synthesizing aldehydes, or the reaction will continue oxidizing to the level of the carboxylic acid.

o   Various oxidizing agents can be used for ketones, such as dichromate, chromium trioxide, or PCC because ketones are the most oxidized functional group for secondary carbons.

Nucleophilic Addition Reactions

·        When a nucleophile attacks and forms a bond with a carbonyl carbon, electrons in the π bond are pushed to oxygen.

o   If there is no good leaving group (aldehydes and ketones), the carbonyl will remain open and is protonated to form an alcohol.

o   If there is a good leaving group (carboxylic acids and derivatives), the carbonyl will reform and kick off the leaving group.

·        In hydration reactions, water adds to a carbonyl, forming a geminal diol.

·        When one equivalent of alcohol reacts with an aldehyde, a hemiacetal is formed. When the same reaction occurs with a ketone, a hemiketal is formed.

·        When another equivalent of alcohol reacts with a hemiacetal (via nucleophilic substitution), an acetal is formed. When the same reaction occurs with a hemiketal, a ketal is formed.

·        Nitrogen and nitrogen derivatives react with carbonyls to form imines, oximes, hydrazones, and semicarbazones. Imines can tautomerize to form enamines.

·        Hydrogen cyanide reacts with carbonyls to form cyanohydrins.

Oxidation–Reduction Reactions

·        Aldehydes can be oxidized to carboxylic acids using an oxidizing agent like KMnO4, CrO3, Ag2O, or H2O2. They can be reduced to secondary alcohols via hydride reagents (LiAlH4, NaBH4).

·        Ketones cannot be further oxidized, but can be reduced to secondary alcohols using the same hydride reagents.

Answers to Concept Checks

·        6.1

1.    The suffix for an aldehyde is –al. The suffix for a ketone is –one.

2.    The alkane will have the lowest boiling point, followed by the aldehyde and then the alcohol. The boiling point of the aldehyde is elevated by its dipole, but the boiling point of an alcohol is further elevated by hydrogen bonding.

3.    The carbon in a carbonyl is electrophilic; it is partially positively charged because oxygen is highly electron-withdrawing.

4.    Aldehydes can be formed by the oxidation of primary alcohols, but can only be produced using weaker (and anhydrous) oxidizing agents like PCC—otherwise, they will oxidize fully to carboxylic acids. Ketones can be formed by the oxidation of secondary alcohols. Other methods can be used as well (ozonolysis, Friedel–Crafts acylation), but these are outside the scope of the MCAT.

·        6.2

1.    With one equivalent of alcohol, aldehydes and ketones will form hemiacetals and hemiketals, respectively. With two equivalents of alcohol, the reaction will run to completion, forming acetals and ketals, respectively.

2.    The reaction that occurs is a condensation reaction because a small molecule is lost, and also a nucleophilic substitution reaction. This reaction results in the formation of an imine (or, for nitrogen-containing derivatives: oximes, hydrazones, or semicarbazones).

3.    When HCN reacts with an aldehyde or ketone, a cyanohydrin is produced, which is a stable product.

·        6.3

1.    Oxidizing an aldehyde yields a carboxylic acid. Common oxidizing agents include KMnO4, CrO3, Ag2O, and H2O2.

2.    Reducing an aldehyde or ketone yields an alcohol. Under certain conditions not tested on the MCAT, aldehydes and ketones can be reduced all the way to alkanes. Common reducing agents include LiAlH4 and NaBH4.

Shared Concepts

·        Biochemistry Chapter 4

o   Carbohydrate Structure and Function

·        General Chemistry Chapter 11

o   Oxidation–Reduction Reactions

·        Organic Chemistry Chapter 1

o   Nomenclature

·        Organic Chemistry Chapter 4

o   Analyzing Organic Reactions

·        Organic Chemistry Chapter 7

o   Aldehydes and Ketones II

·        Organic Chemistry Chapter 8

o   Carboxylic Acids