1

10-03 lecture
Slides are posted. The lecture will be taped tomorrow (Thurs) and posted thereafter. The lecture will complete c16 I will proceed with c17.

Chapter 17: Oxidation

A general class of reactions involves the gain or loss of two electrons, but the structural changes in the product are often measured by whether hydrogen or oxygen is gained or lost. Such reactions are known as oxidation and reduction reactions. Several functional group exchange reactions are classified as oxidations, including the conversion of alcohols to ketones or aldehydes (an oxidation).

To begin, you should know: The structure and basic rules of nomenclature for alcohols, aldehydes, ketones, diols, ethers and carboxylic acids. (chapter 5, sections 5.6, 5.9 and chapter 16, sections 16.2, 16.5) The CIP rules for prioritizing substituents, groups and atoms. (chapter 9, section 9.3) Understand polarized bonds. (chapter 3, section 3.7) Understand !-covalent bonds. (chapter 3, section 3.3) Understand "-bonds. (chapter 5, section 5.1, 5.2) Brnsted-Lowry acids and bases. (chapter 6, section 6.2, 6.3, 6.4) Lewis bases and Lewis acids. (chapter 6, section 6.5) The acid-base properties of alcohols, alkenes, aldehydes and ketones. (chapter 6, sections 6.3, 6.4, 6.5) The fundamental reactions known for alkenes. (chapter 10, sections 102, 10.3, 10.4) Alkenes are converted to epoxides and to diols. (chapter 10, sections 10.5 and 10.7.A) Alkenes undergo oxidative cleavage with ozone. (chapter 10, section 10.7.B) The general reactions of carbonyl compounds. (chapter 16, sections 16.3 and 16.8) E2 type reactions. (chapter 12, sections 12.3 and 12.7)

When completed, you should know:

Oxidation is defined as loss of electrons or gain of a heteroatom such as oxygen

or loss of hydrogen atoms. Oxidation number is a convenient method to track the gain or loss of electrons in a reaction. Chromium (VI) reagents are powerful oxidants. The reaction of a secondary alcohol with chromium trioxide and acid in aqueous acetone is called Jones lc oxidation, and the product is a ketone. Chromium oxidation of an alcohol proceeds by formation of a chromate ester, followed by loss of the !-hydrogen to form the C=O unit. Jones oxidation of a primary alcohol leads to a carboxylic acid in most cases. A mixture of chromium trioxide and pyridine gives a reagent that can oxidize a primary alcohol to an aldehyde. This is called Collins oxidation. The reaction of chromium trioxide and pyridine in aqueous HCl leads to pyridinium chlorochromate, called PCC. The reaction of chromium trioxide and pyridine in water leads to pyridinium dichromate, PDC. Both PCC and PDC can oxidize a secondary alcohol to a ketone, or a primary alcohol to an aldehyde. The oxidation of a secondary alcohol to a ketone or a primary alcohol to an aldehyde using dimethyl sulfoxide (DMSO) with oxalyl chloride at low temperature is called the Swern oxidation.

When completed, you should know:

Oxidation of an alkene with osmium tetroxide or potassium permanganate gives a cis-1,2-diol. Oxidation of an alkene with a peroxyacid leads to an epoxide, with a carboxylic acid as the by-product. Oxidative cleavage of an alkene with ozone leads to an ozonide. Reductive lc workup with dimethyl sulfoxide or zinc and acetic acid gives ketones and/or aldehydes. Oxidative workup with hydrogen peroxide gives ketones and/or carboxylic acids. Oxidative cleavage of 1,2-diols with periodic acid or with lead tetraacetate give aldehydes or ketones.

Oxidation

An oxidation is formally defined as the loss of one or more electrons from an atom or a group. If there are structural changes in the product relative to the starting material, it is possible to associate electron transfer with bond-making and bond-breaking reactions. The structural changes usually include either loss of hydrogen atoms or the replacement of a hydrogen atom bonded to carbon with a more electronegative atom, usually a heteroatom. Such heteroatoms include oxygen, halogen, nitrogen, sulfur, etc. but the most common is oxygen.

Oxidation Number

There is a method that identifies the so-called oxidation state of atoms that is useful for identifying whether electrons are gained or lost during the transformation. Oxidation state is a number is assigned to the carbon atoms involved in the transformation, and the formal rules for determining oxidation state are: (1) The oxidation state of a carbon is taken to be zero. (2) Every hydrogen atom attached to a carbon is given a value of 1. (3) Every heteroatom attached to a carbon is assigned a value of +1.
OH
(0)

CrO3 , H+

O
(+2)

(-1)

KMnO4 , aq. NaOH

(0) (0)

OH OH

H3C

H 1

CH3

H2 O

H3C 2

CH3 3

(-1)

Oxidation Number

In alcohol 1, C2 is attached to two carbon atoms, one hydrogen atom, and one oxygen. The oxidation state of C2 = 0 + 0 1 + 1 = 0 (zero for each carbon, 1 for the hydrogen, and +1 for the oxygen). In the final product, 2, C2 is bonded to two carbon atoms, and it has two bonds to oxygen. The oxidation state of C2 in 2 is calculated by 0 + 0 + 1 + 1 = +2. A comparison of the oxidation state of the pertinent carbon atoms in 1 and in 2 reveals that conversion of 1 to 2 involves a transfer of two electrons. To go from zero to +2 requires that two electrons be lost, since electrons are negatively charged particles. The conversion of 1 to 2 involves the loss of two electrons, and it is an oxidation.

OH
(0)

CrO3 , H+

O
(+2)

H3C

H 1

CH3

H2O

H3C 2

CH3

Oxidation of Alcohols with Chromium (VI): Chromium trioxide

Chromium(VI) is a powerful oxidizing agent and there are several inorganic reagents characterized by the presence of chromium(VI). The most common is chromium trioxide (CrO3), which probably exits in a polymeric form [(CrO3)n], where the n is an integer signifying the number of repeating CrO3 units. Chromium trioxide is usually written as the monomer (the single unit) CrO3, with the structure shown for 5. There are several other reagents that also involve chromium(VI), including chromic acid (HCrO4, 6), sodium dichromate Na2Cr2O7, 7) and potassium dichromate (K2Cr2O7, 8). When chromium trioxide is dissolved in water, a complex equilibrium is established that includes not only 5, but also chromic acid (6) and the protonated form of the dichromate ion (Cr2O7-2).
O O Cr 5 HO O O Cr O 6 O Na O O Cr O 7 O Cr O O Na O KO O Cr O 8 O Cr O OK O

Oxidation of Alcohols with Chromium (VI): Jones Oxidation Alcohols are oxidized by a solution of chromium trioxide in aqueous acetone (2), in the presence of an acid such as H2SO4. This is called the Jones reagent, and the reaction of this mixture with an alcohol is called Jones oxidation. The acetone moderates the reaction and helps to solubilize the various reactions found in this oxidation. In a typical experiment using Na2Cr2O7 in sulfuric acid, 3-pentanol (9) is converted to 3-pentanone (12) in 57% yield. Recognition that in aqueous solution CrO3 is in equilibrium with Cr3O72, allows the use CrO3 as the active oxidizing agent to look at a simplified mechanism.

10

OH 9

Na2Cr2O7 , acetone H+ , water 12

Oxidation of Alcohols with Chromium (VI): Jones Oxidation

11

The oxygen of the alcohol (a Lewis base) donates two electrons to chromium (Cr is a Lewis acid) to form oxonium salt 10. Transfer of the acidic proton of the oxonium salt in 10 to the chromate oxygen (the base) leads to a so-called chromate ester, 11. Formation of the chromate ester makes the hydrogen atom on the !-carbon acidic (marked in red in 11). Removal of that hydrogen by water is an acid-base reaction that leads to loss of the chromium(III) leaving group, which is an elimination reaction that forms a new "-bond; a carbonyl (C=O). If the chromium unit is viewed as a leaving group, then the hydrogen !- to the oxygen is lost to water and the leaving group is CrO3H. This mechanism predicts that the secondary alcohol (9) will be converted to 3-pentanone (12), which is an oxidation. Note the similarity of the oxidation of an alcohol to the elimination reaction of 11 via an E2 reaction (shown in the box) for conversion of an alkyl halide to an alkene. O O H Cr OH O O H Cr O O O CrO3 O - HCrO3 O - H3O+ H H H H O 12 9 10 11 H HO H E2 reaction + HO H + Br

Br

Oxidation of Alcohols with Chromium (VI): Aldehydes

12

Jones oxidation is such a powerful oxidizing medium that unwanted products are possible due to over-oxidation. When a primary alcohol such as 1-pentanol (15) reacts with chromium trioxide and aqueous sulfuric acid, it follows the same mechanistic pathway as 9, with formation of chromate ester 16. Experiments show that the yields of aldehyde from primary alcohols can be very low. 1-Propanol is oxidized to propanal, for example, in only 49% yield, and to obtain the product requires a short reaction time. Very often, a carboxylic acid is formed as a second product or even the major oxidation product rather than the aldehyde. It is known that aldehydes are easily oxidized to carboxylic acids, even by oxygen in the air.

Oxidation of Alcohols with Chromium (VI): Aldehydes

13

Formation of an aldehyde such as 17 in the presence of a powerful oxidizing agent such as chromium(VI), is usually followed by rapid oxidation of 17 to the corresponding carboxylic acid, pentanoic acid (18). In general, Jones oxidation of simple aldehydes usually gives the carboxylic acid as the major product. If the reaction mixture is heated, over-oxidation to the carboxylic acid is even more rapid.

OH

CrO3 , aq. H2 O

H+

OCrO3H

- HCrO3 - H3 O+

H O

CrO3 , aq. H+ H2O heat

OH O 18

15

16

17

Oxidation of Alcohols with Chromium (VI): Aldehydes

14

When acetone is used as a solvent the rate of oxidation of aldehyde to acid is relatively slow. Acetic acid (ethanoic acid) serves a similar role in many oxidations. This means that cold temperatures and short reaction times favor the aldehyde, but long reaction times and heat favor formation of the acid. The reaction of 19 with CrO3 in sulfuric acid and aqueous acetic acid for several hours and then heated to 100C gives carboxylic acid 20 was isolated in 82% yield. If the number molar equivalents of oxidizing agent is diminished, and the temperature is keep low with a short reaction time, aldehyde 21 is isolated in 59% yield.3 In general, assume that oxidation of a secondary alcohol with chromium (VI) leads to a ketone and oxidation of a primary alcohol leads to an aldehyde if temperature and time are controlled.
CHO OH
1.3 CrO3 , H2SO4 2.1 CrO3 , H2SO4 aq. CH3COOH 25C (overnight) 100C (1 h)

COOH

59%

21

aq. CH3COOH 0-5C heat (10 minutes)

82% 20

19

Oxidation of Alcohols with Chromium (VI): Steric Effects

15

Alcohol 22 (2-methyl-3-pentanol) is oxidized faster than alcohol 24 (2,2,4,4-tetramethyl-3-pentanol). If both alcohols are converted to the corresponding chromate ester (23 and 25 respectively), the !-hydrogen (marked in red) must be removed in each case to give the ketone. The surrounding methyl groups in 25 create significant steric hindrance around the !-hydrogen, so it is more difficult for the base (water) to approach that hydrogen. The !-hydrogen in 23 is relatively unhindered and is easily removed by the base, so the rate of oxidation is relatively fast for 23 but slower for 25 due to steric hindrance in the chromate ester. The steric hindrance in the chromate ester makes it more difficult for the water to react with the !proton. Note that the chromate ester is formed in both cases, and the steric hindrance to oxidation occurs in the chromate ester and not in the alcohol.
OH OCrO3H FAST H 22 OH H 23 OH2 OCrO3H SLOW H 24 H 25 OH2 very sterically hindered so
it is difficult for OH2 to collide with H

Oxidation of Alcohols with Chromium (VI): PCC & PDC

16

The reaction of chromium trioxide (5) with pyridine, in aqueous HCl generates a specific compound known as pyridinium chlorochromate (PCC, 31) that is isolated and purified. The CrO3 forms HCrO4 (6) in dilute aqueous acid, which reacts with HCl to form HCrClO3. Pyridine then reacts as a base with this acidic proton to form PCC. If the reaction conditions are modified to increase the amount of pyridine in the water solution. and the HCl is omitted, the reaction generates pyridinium dichromate (PDC, 32), presumably by reaction of an excess of pyridine with H2Cr2O7. In dilute solution, CrO3 is in equilibrium with H2Cr2O7, and pyridine reacts with both acidic hydrogen atoms to produce PDC.

CrO3Cl N H 31 N H 32 2

Cr2O7

-2