Oxidation Reactions – Detailed Study Notes

Definition & General Principles of Oxidation

Traditional definition
• Addition of an electronegative element (usually O) to, or removal of an electropositive element (usually H) from, an organic substrate.
• $\text{Oxidation Level} \uparrow \Longleftrightarrow \text{O content} \uparrow \text{ or } \text{H content} \downarrow$
Modern organic-chemistry view
• Any transformation that increases the proportion of an element more electronegative than C (O, Cl, Br, N, etc.).
• Example: step-wise chlorination of toluene $\text{Ar–CH}3 \;\xrightarrow[]{\text{Cl}2} \;\text{Ar–CH}2\text{Cl} \;\xrightarrow[]{\text{Cl}2} \;\text{Ar–CHCl}2 \;\xrightarrow[]{\text{Cl}2} \;\text{Ar–CCl}_3$
Redox reciprocity
• When the organic compound is oxidised, the oxidant is reduced and vice-versa.

Oxidation of Alkanes

General inertness toward ordinary oxidants (KMnO₄, K₂Cr₂O₇), except when a tertiary C–H is present.
• $\text{(CH}3)3\text{CH} \xrightarrow[523\,\text{K},\,10^3\,\text{atm}]{\text{Cu}} \text{(CH}3)3\text{COH}$ (tert-butyl alcohol)
Selected catalytic/partial oxidations of methane & ethane
• $2\,\text{CH}4 + \text{O}2 \;\xrightarrow[9:1]{\text{Mo}2\text{O}3} \; 2\,\text{CH}3\text{OH}$ • $\text{CH}4 + \tfrac12\,\text{O}2 \;\xrightarrow[]{\text{Mo}2\text{O}3} \; \text{HCHO}+\text{H}2\text{O}$
• $2\,\text{C}2\text{H}6 + 3\,\text{O}2 \;\xrightarrow[\Delta]{(\text{CH}3\text{COO})2\text{Mn}} \; 2\,\text{CH}3\text{COOH}+2\,\text{H}2\text{O}$ • $\text{CH}4+\text{limited }\text{O}2 \xrightarrow[\text{burn}]{\Delta} \text{C} (\text{black})+2\,\text{H}2\text{O}$

Oxidation of Alkenes & Alkynes

Baeyer reagent (cold, dilute, alkaline $\text{KMnO}4$ ) • Converts $C=C$ to a cis-vicinal diol (syn addition). • Mechanistic stereochemistry: both \ce{–OH} enter from the same face. • Generic: >C=C< \;\xrightarrow[\text{OH}^-]{\text{KMnO}4} \; >C(OH)–C(OH)<
• Cyclohexene ⇒ cis-1,2-cyclohexanediol.
$\text{OsO}4/\text{NaHSO}3$
• Same outcome (cis-diol) but milder, higher chemoselectivity; catalytic $\text{OsO}4$ with $\text{H}2\text{O}_2$ as stoichiometric re-oxidant.
Peroxyacids (mCPBA, peroxyacetic, peroxyformic)
• Stage 1: epoxidation (concerted, stereospecific retention of geometry).
>C=C< + \text{RCO}3\text{H} \;\longrightarrow\; \text{epoxide}+\text{RCO}2\text{H}
• Stage 2 (acidic hydrolysis): anti-diol (trans when starting alkene is cis, meso when starting alkene is trans).
Oxidative cleavage with acidic/warm $\text{KMnO}4$ (or $\text{O}3$ fmt not included)
• Terminal $=!CH2$ → $\text{CO}2$ .
• $=!CHR$ → $\text{RCOOH}$ + $\text{CO}2$ . • $=!CR1R2$ → $\text{R}1\text{C=O}+\text{R}2\text{C=O}$ (further oxidation of aldehydic fragments → acids). • Examples – $\text{RCH=CH}2 \xrightarrow[\text{warm}]{\text{KMnO}4/H^+} \text{RCOOH}+\text{CO}2+\text{H}2\text{O}$ – $\text{RC≡CH} \xrightarrow[]{\text{KMnO}4/H^+} \text{RCOOH}+\text{CO}2+\text{H}2\text{O}$
– Internal alkyne $\text{RC≡CR}$ → two carboxylic acids.
• Illustrative cleavages
– $\text{CH}3–C≡C–CH2CH3 \xrightarrow[1]{\text{KMnO}4,\text{OH}^-}\xrightarrow[2]{H^+} \text{CH}3\text{COOH}+\text{CH}3\text{CH}2\text{COOH}$ – $\text{CH}3CH2CH2–C≡CH \rightarrow \text{CH}3CH2CH2\text{COOH}+\text{CO}2+\text{H}_2\text{O}$

Oxidation of Alcohols

Oxidant hierarchy
• Weak: PCC, PDC, anhydrous $\text{CrO}3/pyridine$ , Collins, MnO₂ (selective allylic/benzylic). • Moderate: aqueous $\text{CrO}3$ , Jones reagent, $\text{H}2\text{CrO}4$ .
• Strong: $\text{KMnO}4/H^+/\Delta$ , boiling $\text{K}2\text{Cr}2\text{O}7/H^+$ .
Outcome summary
• 1° alcohol
– Weak → aldehyde.
– Strong → carboxylic acid.
• 2° alcohol
– Any Cr(VI) or Mn(VII) reagent → ketone.
• 3° alcohol
– Resistant; only very vigorous oxidants effect cleavage → mixture of acids/ketones.
Special transformations
• Copper at $\approx 573\,\text{K}$ (dehydrogenation) $\Rightarrow$ aldehyde or ketone; if dehydration dominates, yields alkene.
• Oppenauer oxidation
– $\text{R}2\text{CHOH}+\text{(CH}3)2\text{CO} \xrightarrow[]{\text{Al}(\text{O}^t\text{Bu})3} \text{R}2\text{C=O}+\text{(CH}3)2\text{CH–OH}$ – Reagent base: aluminium tert-butoxide. • Relative ease: \text{RCH}2\text{OH} > \text{R}2\text{CHOH} \gg \text{R}3\text{COH}.
MnO₂ (activated) — chemoselective for allylic & benzylic alcohols ⇒ corresponding carbonyl without affecting other functions.

Carbonyl-Level Oxidations

Aldehydes
• Readily oxidised to same-carbon-count acids by $\text{KMnO}4/H^+$ , $\text{K}2\text{Cr}2\text{O}7/H^+$ .
• Weak oxidants (Ag⁺, Cu²⁺ tests) also suffice.
Ketones
• Oxidation only under harsh conditions; governed by Popoff’s rule—carbonyl stays with smaller alkyl fragment.
– Example: $\text{CH}3\text{COCH}2\text{CH}3 \xrightarrow[\Delta]{\text{KMnO}4/H^+} 2\,\text{CH}3\text{COOH}$ – $\text{CH}3\text{COCH}2\text{CH}2\text{CH}3 \rightarrow \text{CH}3\text{COOH}+\text{CH}3\text{CH}2\text{COOH}$
• Complete oxidation of acetone: $\text{Me–C=O–Me} \rightarrow \text{MeCOOH}+\text{CO}2+\text{H}2\text{O}$ .
Baeyer–Villiger oxidation
• Ketone + peracid → ester; cyclic ketone → lactone.
– $\text{PhCOCH}3 \xrightarrow[]{\text{mCPBA}} \text{PhCOOCH}3$ (67 %).
– $\text{Cyclohexanone} \xrightarrow[\text{BF}3]{\text{H}2\text{O}_2} \text{ε-Caprolactone}$ (62 %).
SeO₂ (allylic oxidation / α-carbonyl oxidation)
• Converts $–CH_2–$ next to >C=O → >C=O (forming 1,2-diketone or α-aldehyde).

Diagnostic Oxidation Tests for Aldehydes

Tollen’s (ammoniacal $\text{Ag}^+$ )
• $\text{RCHO}+2[\text{Ag(NH}3)2]^++3\,\text{OH}^- \rightarrow \text{RCOO}^-+2\,\text{Ag}↓+4\,\text{NH}3+2\,\text{H}2\text{O}$ ⇒ silver mirror.
Fehling’s (alkaline Cu²⁺–tartrate)
• $\text{RCHO}+2\,\text{Cu}^{2+}+3\,\text{OH}^- \rightarrow \text{RCOO}^-+\text{Cu}2\text{O}(\text{red})+2\,\text{H}2\text{O}$
• Benzaldehyde negative.
Benedict’s (Cu²⁺–citrate) – same red Cu₂O precipitate.
Schiff’s reagent (decolourised magenta p-rosaniline)
• Aldehyde restores pink; ketones no colour change.
$\text{HgCl}2$ test (Maquenne) – aldehyde reduces mercuric → mercurous $\text{Hg}2\text{Cl}_2$ (white) or Hg° (grey).

Oxidation of Vicinal Diols (Diol Cleavage)

Periodic acid $\text{HIO}4$ or $\text{NaIO}4/\text{Pb(OAc)}4$ • Forms cyclic periodate ester then cleaves C–C bond, giving carbonyl fragments. • Requires syn–vicinal placement (cis in cyclic systems). • General: $\text{R–CH(OH)–CH(OH)–R'} \xrightarrow[]{\text{HIO}4} \text{R–C=O}+\text{R'–C=O}+\text{HCOOH (if R or R' = H)}$ .
• Trans-diols in rings are inert because ester cannot form.
• Also oxidises α-hydroxy carbonyls, α-dicarbonyls, α-hydroxy acids.

Key Reagents Cheat-Sheet

$\text{KMnO}_4$
• Cold, dilute, basic → syn-diol.
• Warm/acidic → oxidative cleavage.
$\text{OsO}4/\text{NaHSO}3$ – gentle cis-diol.
Peroxyacids – epoxide → trans-diol (after acid).
$\text{CrO}_3$ families
• Jones (aq.), Collins (acetone), PCC (Cl⁻), PDC – tune selectivity for alcohols.
$\text{MnO}_2$ (activated) – allylic/benzylic alcohol → carbonyl.
$\text{SeO}_2$ – allylic CH oxidation or α-carbonyl oxidation.
$\text{HIO}_4$ – vicinal diol cleavage.
Peracids/ $\text{H}2\text{O}2+\text{Lewis acid}$ – Baeyer–Villiger.

Comparative Reactivity & Conceptual Mnemonics

Electron-rich alkenes oxidise faster (give diols/epoxides easier) because the oxidant is electrophilic.
Order of oxidisability
\text{Allylic CH} > 3° CH > 2° CH > 1° CH > CH_4 (for KMnO₄ type reagents).
In cleavage, remember:
• “Carboxylic acids hold onto the carbon that already had O.”
• Terminal C (with ≥2 H) often exits the molecule as $\text{CO}_2$ .

Embedded Worked Examples (from transcript)

$2\,\text{CH}4 + \text{O}2 \rightarrow 2\,\text{CH}_3\text{OH}$ (partial oxidation ratio $9:1$ CH₄:O₂)
$\text{CH}3\text{CH}=\text{CH}–\text{CH(OH)}–\text{CH}2\text{CH}2\text{OH} \xrightarrow[\text{step }1]{\text{K}2\text{Cr}2\text{O}7/H^+} \text{CH}_3\text{CH}=\text{CH}–\text{C(O)OH}+\text{HOOC}–\dots$ (cleavage shown in original problems)
Oppenauer: given allylic alcohol → corresponding conjugated aldehyde.

Ethical & Practical Asides

Strong oxidants (Cr(VI), Mn(VII)) are carcinogenic & environmentally problematic; greener alternatives (IBX, TEMPO, electrochemical) increasingly preferred.
Silver waste from Tollen’s must be retrieved; otherwise forms explosive silver nitride on drying.

Quick-Reference Equations

Syn dihydroxylation: >C=C< \;\xrightarrow[]{\text{KMnO}_4/\text{OH}^-} \; >C(OH)–C(OH)<.
Epoxidation: >C=C< + \text{RCO}3\text{H} \rightarrow \text{epoxide}+\text{RCO}2\text{H}.
Aldehyde test (Tollen): $\text{RCHO}+2[\text{Ag(NH}3)2]^+ +3\,\text{OH}^- \rightarrow \text{RCOO}^- +2\,\text{Ag}+4\,\text{NH}3 +2\,\text{H}2\text{O}$ .
Periodic acid cleavage: $\text{RCH(OH)}–\text{CH(OH)R'}+\text{HIO}_4 \rightarrow \text{RCHO}+\text{R'CHO}+\text{HCOOH}$ (if one side is –CH(OH)).