10-03 lecture1

• Slides are posted.• The lecture will be taped tomorrow (Thurs) andposted thereafter.• The lecture will complete c16• I will proceed with c17.

Chapter 17: Oxidation2

• A general class of reactions involves the gain orloss of two electrons, but the structural changes inthe product are often measured by whether hydrogenor oxygen is gained or lost.• Such reactions are known as oxidation andreduction reactions.• Several functional group exchange reactions areclassified as oxidations, including the conversion ofalcohols to ketones or aldehydes (an oxidation).

To begin, you should know: 3

• The structure and basic rules of nomenclature for alcohols, aldehydes,ketones, diols, ethers and carboxylic acids. (chapter 5, sections 5.6, 5.9 andchapter 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 σ-covalent bonds. (chapter 3, section 3.3)• Understand π-bonds. (chapter 5, section 5.1, 5.2)• Brønsted-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. (chapter6, 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 and10.7.A)• Alkenes undergo oxidative cleavage with ozone. (chapter 10, section 10.7.B)• The general reactions of carbonyl compounds. (chapter 16, sections 16.3 and16.8)• E2 type reactions. (chapter 12, sections 12.3 and 12.7)

When completed, you should know: 4

• Oxidation is defined as loss of electrons or gain of a heteroatom such as oxygenor loss of hydrogen atoms. Oxidation number is a convenient method to trackthe gain or loss of electrons in a reaction.• Chromium (VI) reagents are powerful oxidants. The reaction of a secondaryalcohol with chromium trioxide and acid in aqueous acetone is called Jonesoxidation, and the product is a ketone. Chromium oxidation of an alcoholproceeds by formation of a chromate ester, followed by loss of the α-hydrogen toform 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 aprimary alcohol to an aldehyde. This is called Collins oxidation. The reaction ofchromium trioxide and pyridine in aqueous HCl leads to pyridiniumchlorochromate, called PCC. The reaction of chromium trioxide and pyridine inwater leads to pyridinium dichromate, PDC. Both PCC and PDC can oxidize asecondary 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 analdehyde using dimethyl sulfoxide (DMSO) with oxalyl chloride at lowtemperature is called the Swern oxidation.

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When completed, you should know: 5

• Oxidation of an alkene with osmium tetroxide or potassium permanganategives a cis-1,2-diol.• Oxidation of an alkene with a peroxyacid leads to an epoxide, with a carboxylicacid as the by-product.• Oxidative cleavage of an alkene with ozone leads to an ozonide. Reductiveworkup with dimethyl sulfoxide or zinc and acetic acid gives ketones and/oraldehydes. Oxidative workup with hydrogen peroxide gives ketones and/orcarboxylic acids.• Oxidative cleavage of 1,2-diols with periodic acid or with lead tetraacetate givealdehydes or ketones.

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Oxidation 6

• An oxidation is formally defined as the loss of one or more electronsfrom an atom or a group.• If there are structural changes in the product relative to the startingmaterial, it is possible to associate electron transfer with bond-makingand bond-breaking reactions.• The structural changes usually include either loss of hydrogen atoms orthe replacement of a hydrogen atom bonded to carbon with a moreelectronegative atom, usually a heteroatom.• Such heteroatoms include oxygen, halogen, nitrogen, sulfur, etc. butthe most common is oxygen.

Oxidation Number 7

• There is a method that identifies the so-called oxidation state of atomsthat is useful for identifying whether electrons are gained or lost duringthe transformation.• Oxidation state is a number is assigned to the carbon atoms involved inthe transformation, and the formal rules for determining oxidation stateare:

(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.

H3C

OH

CH3H OH

OH

H3C

O

CH3

CrO3 , H+ KMnO4 , aq. NaOH

1 2 3 4

(0)(-1)

(+2)(0)

(0)(-1)H2O

Oxidation Number 8

• 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 thehydrogen, and +1 for the oxygen).• In the final product, 2, C2 is bonded to two carbon atoms, and it has two bonds tooxygen. 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 revealsthat 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 arenegatively charged particles.• The conversion of 1 to 2 involves the loss of two electrons, and it is an oxidation.

H3C

OH

CH3H H3C

O

CH3

CrO3 , H+

1 2

(0)(+2)H2O

Oxidation of Alcohols with Chromium (VI):Chromium trioxide

9

• Chromium(VI) is a powerful oxidizing agent and there are several inorganicreagents characterized by the presence of chromium(VI).• The most common is chromium trioxide (CrO3), which probably exits in apolymeric form [(CrO3)n], where the “n” is an integer signifying the number ofrepeating CrO3 units.• Chromium trioxide is usually written as the monomer (the single unit) CrO3, withthe structure shown for 5.• There are several other reagents that also involve chromium(VI), including chromicacid (HCrO4, 6), sodium dichromate Na2Cr2O7, 7) and potassium dichromate(K2Cr2O7, 8).• When chromium trioxide is dissolved in water, a complex equilibrium is establishedthat includes not only 5, but also chromic acid (6) and the protonated form of thedichromate ion (Cr2O7

-2).

OCr

O

OHO Cr

O

O

O

Cr

O

O

O OCr

O

O

O

Cr

O

O

O OCr

O

O

O5 6 7 8

Na K

KNa

Oxidation of Alcohols with Chromium (VI): Jones Oxidation10

• Alcohols are oxidized by a solution of chromium trioxide in aqueous acetone (2), inthe presence of an acid such as H2SO4.• This is called the Jones reagent, and the reaction of this mixture with an alcohol iscalled Jones oxidation.• The acetone moderates the reaction and helps to solubilize the various reactionsfound in this oxidation.• In a typical experiment using Na2Cr2O7 in sulfuric acid, 3-pentanol (9) is convertedto 3-pentanone (12) in 57% yield.• Recognition that in aqueous solution CrO3 is in equilibrium with Cr3O7

–2, allowsthe use CrO3 as the active oxidizing agent to look at a simplified mechanism.

O

12

OH

9

Na2Cr2O7 , acetone

H+ , water

Oxidation of Alcohols with Chromium (VI): Jones Oxidation11

• The oxygen of the alcohol (a Lewis base) donates two electrons to chromium (Cr is a Lewis acid) to formoxonium salt 10.• Transfer of the acidic proton of the oxonium salt in 10 to the chromate oxygen (the base) leads to a so-calledchromate ester, 11.• Formation of the chromate ester makes the hydrogen atom on the α-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) leavinggroup, which is an elimination reaction that forms a new π-bond; a carbonyl (C=O). If the chromium unit isviewed as a leaving group, then the hydrogen α- to the oxygen is lost to water and the leaving group isCrO3H.• This mechanism predicts that the secondary alcohol (9) will be converted to 3-pentanone (12), which is anoxidation. Note the similarity of the oxidation of an alcohol to the elimination reaction of 11 via an E2reaction (shown in the box) for conversion of an alkyl halide to an alkene.

OH

H

OCr

H

O

O

OH OCr

H

O

O

OH

9 10 11

O

12OH

H

- HCrO3CrO3

- H3O+

Br

H E2 reaction+ HO H Br–+

HO–

Oxidation of Alcohols with Chromium (VI): Aldehydes12

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

Oxidation of Alcohols with Chromium (VI): Aldehydes13

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

OH OCrO3H

15 16O

17

H

O18

OHCrO3 , aq. H+ - HCrO3 CrO3 , aq. H+

heatH2O - H3O+ H2O

Oxidation of Alcohols with Chromium (VI): Aldehydes14

• 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 longreaction 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 thenheated to 100°C gives carboxylic acid 20 was isolated in 82% yield.• If the number molar equivalents of oxidizing agent is diminished, and the temperature is keeplow 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 aketone and oxidation of a primary alcohol leads to an aldehyde if temperature and time arecontrolled.

OH COOHCHO2.1 CrO3 , H2SO4

aq. CH3COOH25°C (overnight)100°C (1 h)

82%

1.3 CrO3 , H2SO4

aq. CH3COOH0-5°C heat (10 minutes)

59% 19 2021

Oxidation of Alcohols with Chromium (VI): Steric Effects15

• 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 α-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 α-hydrogen, so it is moredifficult for the base (water) to approach that hydrogen.• The α-hydrogen in 23 is relatively unhindered and is easily removed by the base, so the rate of oxidation isrelatively 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 α-proton.• Note that the chromate ester is formed in both cases, and the steric hindrance to oxidation occurs in thechromate ester and not in the alcohol.

OH

H

H

OH

22

24

OCrO3H

H

H

OCrO3H

23

25

O

very sterically hindered so it is difficult for OH2 to collide with H

OSLOW

OH2

OH2

FAST

Oxidation of Alcohols with Chromium (VI): PCC & PDC16

• The reaction of chromium trioxide (5) with pyridine, in aqueous HCl generates aspecific compound known as pyridinium chlorochromate (PCC, 31) that is isolatedand purified.• The CrO3 forms HCrO4 (6) in dilute aqueous acid, which reacts with HCl to formHCrClO3. 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 thewater 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 withboth acidic hydrogen atoms to produce PDC.

N

H

N

H2

-2

31 32

CrO3ClCr2O7