Source: LT5 Worksheet, Brown textbook Ch. 6, 10, 11
Tags: oxidation, alcohol oxidation, alkene oxidation, Jones, PCC, Dess-Martin, Swern, ozonolysis, epoxidation, mCPBA
Difficulty: Intermediate | Prerequisites: Redox Fundamentals (Part 1 of these notes), functional groups, alcohol classification (1°, 2°, 3°), alkene structure, stereochemistry basics (cis/trans, syn/anti addition).
Oxidation reactions convert lower-oxidation-state functional groups into higher ones: alcohols become aldehydes, ketones, or carboxylic acids; alkenes are cleaved or converted to epoxides. These transformations are central to organic synthesis because they let you build up the oxygen-containing functional groups found in pharmaceuticals, natural products, and industrial chemicals. Reagent choice controls selectivity: the wrong oxidiser over-oxidises a primary alcohol to a carboxylic acid when you wanted the aldehyde. This section covers the five major oxidation methods in CHEM 212: Jones oxidation, PCC, Dess-Martin, Swern, ozonolysis, and epoxidation.
Chromium reagents (Jones) oxidise primary alcohols all the way to carboxylic acids; PCC, Dess-Martin, and Swern stop at the aldehyde. Secondary alcohols give ketones with any of these reagents. Tertiary alcohols cannot be oxidised (no alpha hydrogen). Ozonolysis cleaves C=C double bonds to give two carbonyl fragments. Epoxidation with a peroxyacid (mCPBA) converts alkenes to epoxides with retained stereochemistry (syn addition).
Jones oxidation
Oxidation of an alcohol using chromic acid (H₂CrO₄), prepared in situ from potassium dichromate (K₂Cr₂O₇) and sulfuric acid in water. Oxidises 1° alcohols to carboxylic acids and 2° alcohols to ketones.
Think of it as: the "strong" chromium oxidation that goes all the way because water is present.
PCC (pyridinium chlorochromate)
A milder chromium-based oxidising agent used in anhydrous dichloromethane (DCM, CH₂Cl₂). Oxidises 1° alcohols to aldehydes only (no further) and 2° alcohols to ketones.
Think of it as: the "gentle" chromium oxidant that stops at the aldehyde because there is no water to form a hydrate.
Dess-Martin periodinane (DMP)
A hypervalent iodine reagent that oxidises 1° alcohols to aldehydes and 2° alcohols to ketones. A "green" alternative to chromium reagents (no toxic heavy metals).
In simple terms: a non-toxic replacement for PCC that does the same job.
Swern oxidation
Oxidation using oxalyl chloride and dimethyl sulfoxide (DMSO), followed by triethylamine (Et₃N). Oxidises 1° alcohols to aldehydes and 2° alcohols to ketones.
In simple terms: another chromium-free option. The active species is a chlorosulfonium salt.
Ozonolysis
Cleavage of a C=C double bond using ozone (O₃), followed by a reductive workup with dimethyl sulfide (DMS) or zinc (Zn). The double bond is cut and each carbon gets an oxygen, producing aldehydes and/or ketones.
Think of it as: molecular scissors that snip a double bond and cap each end with =O.
Epoxidation
Conversion of an alkene to an epoxide (a three-membered ring containing oxygen) using a peroxyacid. The reaction is a syn addition, and stereochemistry is conserved.
In simple terms: the double bond picks up an oxygen atom to form a small, strained ring.
Peroxyacid
A carboxylic acid with an extra oxygen in the O–O–H group (R–CO₃H). The weak O–O bond is the source of the oxygen atom transferred to the alkene.
mCPBA (meta-chloroperoxybenzoic acid)
The most commonly used peroxyacid in the lab for epoxidation. Also written as m-CPBA.
Chromate ester
The intermediate formed when an alcohol reacts with chromic acid. The alcohol's oxygen bonds to chromium, forming an ester-like species. An elimination step then removes the alpha hydrogen and chromium leaves as Cr(IV), producing the carbonyl.
Chromic acid (H₂CrO₄) oxidises alcohols via a two-step process: substitution to form a chromate ester, then elimination to produce the carbonyl.
How the mechanism works (overview only, not required to reproduce):
The alcohol oxygen attacks chromium, displacing a leaving group (substitution). This produces the chromate ester intermediate.
A base removes the alpha hydrogen while the C–O bond to chromium breaks (elimination, similar to an E2 with a good leaving group). The result is a C=O bond.
Why Jones oxidation over-oxidises primary alcohols:
The reaction is run in aqueous acid. When a 1° alcohol is oxidised to an aldehyde, the aldehyde equilibrates with its hydrate (gem-diol) in water. The hydrate has a C–OH bond that chromic acid can oxidise again, pushing the product further to the carboxylic acid.
1° alcohol → aldehyde → (hydrate in water) → carboxylic acid
Secondary alcohols give ketones:
A 2° alcohol is oxidised to a ketone. Ketones do not have the same over-oxidation problem because the hydrate of a ketone is less readily formed, and there is no C–H bond on the carbonyl carbon to lose.
Tertiary alcohols cannot be oxidised:
The elimination step requires an alpha hydrogen (the H on the carbon bearing the OH). Tertiary alcohols have no such hydrogen, so the chromate ester forms but the elimination cannot proceed. No reaction.
Real-world application: Breathalysers use chromic acid to oxidise ethanol in breath to acetic acid. The colour change from orange Cr⁶⁺ to green Cr⁴⁺ is proportional to blood-alcohol content.
PCC (pyridinium chlorochromate) is used in dichloromethane (DCM, CH₂Cl₂), which is anhydrous (no water). Because there is no water, the aldehyde product cannot form a hydrate. Without a hydrate, there is nothing for the oxidant to attack a second time.
1° alcohol + PCC/DCM → aldehyde (stops here)
2° alcohol + PCC/DCM → ketone
3° alcohol + PCC/DCM → no reaction
The key insight is the solvent. Jones uses aqueous acid (water present, over-oxidation occurs). PCC uses dry DCM (no water, oxidation stops at the aldehyde). Same chromium chemistry, different outcome because of the medium.
Chromium reagents are toxic and produce hazardous waste. Two widely used alternatives avoid heavy metals entirely.
Dess-Martin periodinane (DMP)
A hypervalent iodine(V) compound. The alcohol displaces one of the acetate groups on iodine, forming a diacetoxyalkoxy periodinane intermediate. Elimination then gives the carbonyl product plus acetic acid (HOAc) as a by-product.
1° alcohol + DMP → aldehyde
2° alcohol + DMP → ketone
Swern oxidation
Uses oxalyl chloride (COCl)₂ and DMSO to generate a chlorosulfonium salt, which reacts with the alcohol. Treatment with triethylamine (Et₃N) triggers elimination to give the carbonyl.
1° alcohol + Swern conditions → aldehyde
2° alcohol + Swern conditions → ketone
Both DMP and Swern behave like PCC in terms of selectivity: they stop at the aldehyde for primary alcohols. Neither can oxidise tertiary alcohols (same alpha-hydrogen requirement).
Ozonolysis is one of the few organic reactions that breaks C–C bonds. Ozone (O₃) attacks the alkene, and after a reductive workup with dimethyl sulfide (DMS) or zinc, the double bond is cleaved and each carbon receives an oxygen (=O).
The method:
Treat the alkene with O₃.
Work up with (CH₃)₂S (DMS) or Zn.
What you get:
Imagine cutting the double bond with scissors and capping each end with =O.
A disubstituted end of the double bond → ketone
A monosubstituted or unsubstituted end → aldehyde
Examples from the worksheet:
A trisubstituted alkene treated with O₃/DMS gives one ketone fragment and one aldehyde fragment.
A cyclohexene ring treated with O₃/DMS gives a single linear dialdehyde (the ring opens when the C=C is cut).
Retrosynthesis (working backwards):
If you are given the ozonolysis products and asked to find the starting alkene, mentally remove the =O from each fragment and join the two carbons with a double bond.
For example, if the product is a keto-aldehyde chain, the starting material was a cyclic alkene whose ring contained the double bond.
Real-world application: Ozone is used as an air and water sanitiser. Ozone generators are common in auto detailing to disinfect car interiors, exploiting ozone's power as an oxidising agent that destroys bacteria and viruses.
Epoxidation converts an alkene into an epoxide (oxirane), a strained three-membered ring with one oxygen atom. The reagent is a peroxyacid, most commonly mCPBA (meta-chloroperoxybenzoic acid) or peracetic acid (CH₃CO₃H).
Key features:
Syn addition: The oxygen is delivered to one face of the double bond. Both new C–O bonds form on the same side.
Stereospecific: The stereochemistry of the alkene is conserved in the product. A trans alkene gives a trans-epoxide. A cis alkene gives a cis-epoxide.
Concerted mechanism: The peroxyacid transfers its oxygen to the alkene in a single step (no intermediates, no carbocation).
Stereochemistry examples from the worksheet:
trans-2-butene + mCPBA → trans-epoxide (H and CH₃ groups remain trans to each other across the ring).
cis-2-butene + mCPBA → cis-epoxide (H and CH₃ groups remain cis).
Reactivity of epoxides:
Epoxides are good electrophiles because of ring strain (the 60° bond angles are far from the ideal 109.5° for sp³ carbon). Nucleophiles attack the less-substituted carbon of the epoxide in an SN2 fashion, opening the ring with inversion at the attacked carbon.
Real-world application: Ethylene oxide (the simplest epoxide, also called oxirane) is an industrial precursor to ethylene glycol (antifreeze) and is a building block for polyethylene glycol (PEG) polymers.
Students often think PCC and Jones give the same product. They do not for primary alcohols. Jones (aqueous) over-oxidises to carboxylic acid; PCC (anhydrous DCM) stops at aldehyde.
Students assume that ozonolysis always gives two separate molecules. When the alkene is in a ring, ozonolysis opens the ring and produces a single dicarbonyl chain instead.
Students confuse epoxidation with dihydroxylation. Epoxidation gives a three-membered ring with one oxygen; dihydroxylation (e.g. OsO₄) gives a diol with two OH groups. Different reagent, different product.
Students forget that tertiary alcohols are inert to all these oxidation reagents. The mechanism requires an alpha hydrogen for the elimination step.
⚠️ Know the reagent-product table cold: Jones → carboxylic acid (1°) or ketone (2°); PCC/DMP/Swern → aldehyde (1°) or ketone (2°); all → no reaction (3°).
⚠️ Ozonolysis retrosynthesis questions are common: given the products, reconstruct the starting alkene by joining the carbonyl carbons with a C=C.
⚠️ Epoxidation stereochemistry will be tested. Know that trans-alkene → trans-epoxide and cis-alkene → cis-epoxide (stereospecific syn addition).
⚠️ Be able to explain why PCC stops at the aldehyde (anhydrous conditions, no hydrate formation) and why Jones goes further (aqueous conditions, hydrate forms and is re-oxidised).
Fill in the blank: PCC in DCM oxidises a primary alcohol to an ______. (aldehyde)
True or false: Jones oxidation of a secondary alcohol gives a carboxylic acid. (False, it gives a ketone.)
Fill in the blank: Ozonolysis of a trisubstituted alkene gives a ______ and an ______. (ketone, aldehyde)
True or false: Epoxidation with mCPBA is an anti addition. (False, it is a syn addition.)
Fill in the blank: Tertiary alcohols cannot be oxidised because they lack an ______ hydrogen. (alpha)
Q: You treat 1-butanol with H₂CrO₄ / H₂SO₄ / H₂O. What is the product?
A: Butanoic acid (a carboxylic acid). Jones conditions oxidise primary alcohols all the way because the aldehyde intermediate forms a hydrate in water, which is oxidised again.
Q: You treat 1-butanol with PCC in DCM. What is the product?
A: Butanal (an aldehyde). PCC in anhydrous DCM stops at the aldehyde because no hydrate forms.
Q: Draw the products of ozonolysis (O₃, then DMS) of cyclohexene.
A: A single linear six-carbon dialdehyde, OHC–(CH₂)₄–CHO. The ring opens when the double bond is cleaved, and each end of the former C=C receives a =O.
Q: cis-2-butene is treated with mCPBA. Draw the product and specify the stereochemistry.
A: cis-2,3-epoxybutane. The H and CH₃ groups that were cis in the alkene remain cis in the epoxide (stereochemistry is conserved, syn addition).
Q: Why can Dess-Martin periodinane replace PCC in most synthetic routes?
A: DMP gives the same products (aldehyde from 1° alcohol, ketone from 2° alcohol) without using toxic chromium. It is milder, works at room temperature, and produces only acetic acid as a by-product.
Alcohol oxidation connects to LT7/LT8 (nucleophilic addition to carbonyls), since the aldehydes and ketones you make here are the starting materials for those reactions. Ozonolysis is a key retrosynthetic tool: if you see a dicarbonyl in a target molecule, consider whether the starting material was an alkene. Epoxidation links to ring-opening reactions (SN2) and to dihydroxylation (a different syn addition that gives diols instead of epoxides).
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