Basic Organic Chemistry

2302202 Aldehydes and Ketones: Oxidation-Reduction Reactions Dr Christopher Smith Office: MHMK 905/2

J. G. Smith, Organic Chemistry, Chapters 12, 20, 21

Lecture Outline •Oxidation and Reduction of Organic Molecules •Oxidation Reactions •Reduction Reactions

Oxidation and Reduction of Organic Molecules • Oxidation results in an increase in the number of C–Z bonds (usually C–O bonds) or a decrease in the number of C–H bonds. • Reduction results in a decrease in the number of C–Z bonds (usually C–O bonds) or an increase in the number of C–H bonds.


Oxidation Reactions


Preparation of Aldehydes


Preparation of Ketones


Oxidation of Alcohols • Alcohols are oxidized to a variety of carbonyl compounds.


Oxidation of 1° Alcohols • Primary alcohols are oxidized to either aldehydes or carboxylic acids, depending on the reagent.


Oxidizing Agents with Metal Oxygen Bonds • The most common oxidizing agents with metal–oxygen bonds contain either chromium +6 or manganese +7. • Common Cr6+ reagents include CrO3 and sodium or potassium dichromate (Na2Cr2O7 and K2Cr2O7). • Pyridinium chlorochromate (PCC) is a more selective Cr6+ oxidant.

• The most common Mn7+ reagent is KMnO4 (potassium permanganate). • Other oxidizing agents that contain metals include OsO4 (osmium tetroxide) and Ag2O [silver(I) oxide].


Chromium Oxidizing Reagents • Oxidation of alcohols to carbonyl compounds is typically carried out with Cr6+ oxidants, which are reduced to Cr3+ products. • CrO3, Na2Cr2O7, and K2Cr2O7 are strong, nonselective oxidants used in aqueous acid (H2SO4 + H2O). • PCC is soluble in CH2Cl2 (dichloromethane) and can be used without strong acid present, making it a more selective, milder oxidant.


Mechanism of CrO3 Oxidation


Mechanism of Oxidation of 1° Alcohols


Oxidation of 2° Alcohols • Any of the Cr6+ oxidants effectively oxidize 2° alcohols to ketones.


Oxidation of Alcohols-Summary • Alcohols are oxidized to a variety of carbonyl compounds.


Oxidation and Reduction of Carbonyl Compounds • The three most useful oxidation and reduction reactions of carbonyl starting materials can be summarized as follows:


Oxidation of Aldehydes • A variety of oxidizing agents can be used, including CrO3, Na2Cr2O7, K2Cr2O7, and KMnO4. • Aldehydes can also be oxidized selectively in the presence of other functional groups using silver(I) oxide in aqueous ammonium hydroxide (Tollen’s reagent). • Since ketones have no H on the carbonyl carbon, they do not undergo this oxidation reaction.


Reductions of Organic Molecules • There are three types of reductions differing in how H2 is added. • The simplest reducing agent is H2. Reductions using H2 are carried out with a metal catalyst. • A second way is to add two protons and two electrons to a substrate—that is, H2 = 2H+ + 2e−. • Reductions of this sort use alkali metals as a source of electrons and liquid ammonia as a source of protons. • These are called dissolving metal reductions.


Catalytic Hydrogenation of Carbonyls • Catalytic hydrogenation also reduces aldehydes and ketones to 1° and 2° alcohols, respectively, using H2 and a catalyst

• When a compound contains both a carbonyl group and a carbon–carbon double bond, selective reduction of one functional group can be achieved by proper choice of the reagent • A C=C is reduced faster than a C=O with H2 (Pd–C) • A C=O is readily reduced with NaBH4 and LiAlH4, but a C=C is inert 18

Comparison of Carbonyl ReductionsSummary • For example, 2-cyclohexenone, which contains both a C=C and a C=O, can be reduced to three different compounds depending upon the reagent used


Hydride Reduction • Addition of H2 through adding hydride (H¯) and a proton (H+) • The most common hydride reducing agents contain a hydrogen atom bonded to boron or aluminum. • Simple examples include sodium borohydride (NaBH4) and lithium aluminum hydride (LiAlH4). • NaBH4 and LiAlH4 deliver H¯ to the substrate, and then a proton is added from H2O or an alcohol.


Nucleophilic Addition Reactions


Reduction of Aldehydes and Ketones • The most useful reagents for reducing aldehydes and ketones are the metal hydride reagents

• Treating an aldehyde or ketone with NaBH4 or LiAlH4, followed by H2O or some other proton source affords an alcohol


Nucleophilic Addition of Hydride • Treatment of an aldehyde or ketone with either NaBH4 or LiAlH4 followed by protonation forms a 1° or 2° alcohol.

• Hydride reduction occurs via a two-step mechanism.


Metal Hydride Reduction of Carbonyls

• The net result of adding H:− (from NaBH4 or LiAlH4) and H+ (from H2O) is the addition of the elements of H2 to the carbonyl  bond 24

Sodium Borohydride Reductions in Synthesis


Stereochemistry of Carbonyl Reduction • Hydride converts a planar sp2 hybridized carbonyl carbon to a tetrahedral sp3 hybridized carbon