1 Chapter 12 Oxidation and Reduction

2 Oxidation Oxidation results in an increase in the number of C—Z bonds; or Oxidation results in a decrease in the number of C—H bonds. Reduction results in a decrease in the number of C—Z bonds; or Reduction results in an increase in the number of C—H bonds. Chapter 4

3 Oxidation and Reduction Sometimes two carbon atoms are involved in a single oxidation or reduction reaction, and the net change in the number of C—H or C—Z bonds at both atoms must be taken into account. Introduction XX

4 Oxidation and Reduction Addition of molecular hydrogen: with a metal catalyst. Addition of two protons and two electrons: H 2 = 2H + + 2e -. dissolving metal reductions. Addition of a hydride (H - ) and a proton (H + ): sodium borohydride (NaBH 4 ) lithium aluminum hydride (LiAlH 4 ). Reducing Agent: one that is oxidized

5 Oxidation and Reduction catalytic hydrogenation : metal catalyst is required catalyst : Pd, Pt, or Ni, adsorbed onto a finely divided inert solid, such as charcoal. H 2 adds in a syn fashion. Reduction of Alkenes—Catalytic Hydrogenation heterogeneous reaction

6 Oxidation and Reduction Reduction of Alkenes—Catalytic Hydrogenation When hydrogenation of two alkenes gives the same alkane, the more stable alkene has the smaller heat of hydrogenation.

7 Oxidation and Reduction Catalytic Hydrogenation : reversible !

8 Oxidation and Reduction The mechanism explains two facts about hydrogenation: Reduction of Alkenes—Catalytic Hydrogenation

9 Application : Structural Determination

10 Oxidation and Reduction Reduction of other double bonds Inert except with stronger catalyst like Raney-Ni Slow

11 Oxidation and Reduction Reduction of Alkynes

12 Oxidation and Reduction Alkane formation: Reduction of an Alkyne to an Alkane

13 Oxidation and Reduction To stop at a cis alkene, a less active Pd catalyst is used— Pd adsorbed onto CaCO 3 with added lead(II) acetate and quinoline. This is called Lindlar’s catalyst. Reduction of an Alkyne to a Cis Alkene

14 Oxidation and Reduction Reduction of an alkyne to a cis alkene is a stereoselective reaction, because only one stereoisomer is formed. Reduction of an Alkyne to a Cis Alkene

15 Oxidation and Reduction dissolving metal reduction (such as Na in NH 3 ), forms a trans alkene. adding electrons one at a time. Reduction of an Alkyne to a Trans Alkene

16 Reduction of an Alkyne to a Trans Alkene: Mechanism

17 Oxidation and Reduction Summary of Alkyne Reductions

18 Oxidation and Reduction Alkyl halides can be reduced to alkanes with LiAlH 4. Epoxide rings can be opened with LiAlH 4 to form alcohols. Reduction of Polar C—X  Bonds

19 Oxidation and Reduction Reduction of Polar C—X  Bonds This reaction follows an S N 2 mechanism. Unhindered CH 3 X and 1 ° alkyl halides are more easily reduced than more substituted 2 ° and 3 ° halides. In unsymmetrical epoxides, nucleophilic attack of H ¯ (from LiAlH 4 ) occurs at the less substituted carbon atom.

20 Summary of Reductions

21 Oxidation and Reduction Oxidizing Reactions

22 Oxidation and Reduction There are two main categories of oxidizing agents: 1.Reagents that contain an oxygen-oxygen bond 2.Reagents that contain metal-oxygen bonds Oxidizing agents containing an O—O bond include O 2, O 3 (ozone), H 2 O 2 (hydrogen peroxide), (CH 3 )COOH (tert-butyl hydroperoxide), and peroxyacids. Peroxyacids (or peracids) have the general formula RCO 3 H. Oxidizing Agents (that deliver oxygen atom or take hydrogen atom)

23 Oxidation and Reduction Mostly chromium +6 (six Cr—O bonds) or manganese +7 (seven Mn—O bonds). Common Cr 6 + reagents include CrO 3 and sodium or potassium dichromate (Na 2 Cr 2 O 7 and K 2 Cr 2 O 7 ). Pyridinium chlorochromate (PCC) is a more selective Cr 6+ oxidant. Oxidizing Agents KMnO 4 (potassium permanganate), MnO 2. OsO 4 (osmium tetroxide) and Ag 2 O [silver(I) oxide].

24 Oxidation and Reduction Alcohols are oxidized to a variety of carbonyl compounds. Oxidation of Alcohols

25 Oxidation and Reduction CrO 3, Na 2 Cr 2 O 7, and K 2 Cr 2 O 7 are strong, nonselective oxidants used in aqueous acid (H 2 SO 4 + H 2 O). PCC is soluble in CH 2 Cl 2 (dichloromethane) and can be used without strong acid present, making it a more selective, milder oxidant. Oxidation of Alcohols: mostly chromium reagents

26 Oxidation and Reduction Any of the Cr 6+ oxidants effectively oxidize 2° alcohols to ketones. Oxidation of 2 ° Alcohols

27 Oxidation and Reduction 1° Alcohols are oxidized to either aldehydes or carboxylic acids, depending on the reagent. Oxidation of 1 ° Alcohols

28 Oxidation and Reduction Oxidation of 1 ° Alcohols

29 Oxidation and Reduction Epoxidation is the addition of a single oxygen atom to an alkene to form an epoxide. Epoxidation is typically carried out with a peroxyacid. Epoxidation

30 Oxidation and Reduction a cis alkene gives an epoxide with cis substituents. A trans alkene gives an epoxide with trans substituents. Epoxidation This reaction is stereospecific because cis and trans alkenes yield different stereoisomers as products. more substituted, electron rich alkenes react faster.

Epoxidation

32 Oxidation and Reduction Disparlure, the sex pheromone of the gypsy moth. Carterpillars of gypsy moth eats leaves of broadleaf trees Use: attract and trap male moths. Retrosynthetic analysis of disparlure illustrates three key operations: The Synthesis of Disparlure

33 Oxidation and Reduction The Synthesis of Disparlure

34 Oxidation and Reduction Dihydroxylation is the addition of two hydroxy groups to a double bond, forming a 1,2-diol or glycol. Dihydroxylation

35 Oxidation and Reduction Anti dihydroxylation : two steps—epoxidation, followed by ring opening with ¯ OH or H 3 O +. Dihydroxylation

36 Oxidation and Reduction Syn hydroxylation : with either KMnO 4 or OsO 4. Dihydroxylation Insoluble in organic solvent

37 Oxidation and Reduction Each reagent adds two oxygen atoms in a syn fashion. Dihydroxylation

38 Oxidation and Reduction Dihydroxylation with a catalytic amount of OsO 4 : the oxidant N- methylmorpholine N-oxide (NMO) Dihydroxylation : catalytic version

39 Oxidation and Reduction Oxidative cleavage forms two carbonyl compounds. Cleavage with ozone (O 3 ) is called ozonolysis. Oxidative Cleavage of Alkenes

40 Oxidative Cleavage of Alkenes : mechanism

41 Oxidation and Reduction Ozonolysis of dienes or other polyenes results in oxidative cleavage of all C=C bonds. It is important to note that when oxidative cleavage involves a double bond that is part of a ring, the ring opens up affording a single chain with two carbonyls at the carbons where the double bonds were originally. Oxidative Cleavage of Alkenes

42 Oxidation and Reduction Alkynes undergo oxidative cleavage of the  and both  bonds. Internal alkynes are oxidized to carboxylic acids (RCOOH). Oxidative Cleavage of Alkynes

43 Oxidation and Reduction Green chemistry : use of environmentally benign methods to synthesize compounds i.e. to use safer reagents and less solvent, and develop reactions that form fewer by-products and generate less waste. many oxidation methods use toxic reagents (such as OsO 4 and O 3 ) and corrosive acids such as H 2 SO 4, or generate carcinogenic by-products (such as Cr 3+ ). One methods uses a polymer supported Cr 3+ reagent— Amberlyte A-26 resin-HCrO 4 —that avoids the use of strong acid, and forms a Cr 3+ by-product that can easily be removed from the product by filtration. Green Chemistry

44 Oxidation and Reduction With Amberlyst A-26 resin-HCrO 4 ¯, 1° alcohols are oxidized to aldehydes and 2° alcohols are oxidized to ketones. Green Chemistry

45 In the body, ingested ethanol is oxidized in the liver first to CH 3 CHO (acetaldehyde), and then to CH 3 COO ¯ (the acetate anion). This oxidation is catalyzed by alcohol dehydrogenase. If more ethanol is ingested than can be metabolized, the concentration of acetaldehyde increases. Acetaldehyde, which is toxic, is responsible for the feelings associated with a hangover. If methanol is ingested, it is metabolized by the same enzyme to formaldehyde and formic acid. These compounds are extremely toxic since they cannot be used by the body. Blood pH decreases, and blindness and death can follow. The Oxidation of Ethanol

, 12.42, 12.43, 12.50, 12.51, 12.52, 12.58, 12.60, Homework

47 Preview of Chapter 13 and 14 Organic Structural Identification : NMR, IR, UV, MS What information can you obtain from MS? What does IR spectroscopy measure? What does 1 H-NMR provide to determine the molecular structure?