Alkenes – Comprehensive Synthesis & Reaction Notes

Synthesis of Alkenes

• β–Elimination is the dominant strategy for making C=C bonds.
  • Two atoms/groups on adjacent (α / β) carbons are removed → new $\pi$ bond forms.
  • Parent reactions: dehydrohalogenation, dehalogenation, dehydration.

1. Dehydrohalogenation of Alkyl Halides (E2)

• Conditions: strong alcoholic base (e.g.
  • $\mathrm{KOH(alc)}$
  • $\mathrm{C<em>2H</em>5ONa}$).
• Concerted, anti-periplanar transition state; no carbocation.
• Base abstracts β-H → electrons create C=C as leaving group X departs.
• Zaitsev (Saytzeff) rule predominates:
  • Major = most substituted alkene (more stable, lower $\Delta G_{\text{f}}$).
  • Minor (Hofmann) = less substituted/terminal alkene.
• Trans > cis stereochemical outcome because trans is thermodynamically favored.
• Stereochemistry determined by anti-periplanar requirement (E2).

2. Dehalogenation of Vicinal Dihalides

• Reagents/conditions:
  • $\mathrm{NaI/acetone}$ (iodide acts as nucleophile)
  • $\mathrm{Zn/CH<em>3COOH}$ (reductive elimination → $\mathrm{ZnBr</em>2}$ side-product).
• Mechanistic outline:
  • Iodide/Zn inserts, one X leaves, electrons collapse to C=C, second X leaves.
  • Works best for vic-dibromides or vic-dichlorides.

3. Dehydration of Alcohols

• Acidic elimination of \ce{H2O}.
  • Acids: conc \ce{H2SO4}, \ce{H3PO4}.
  • 3° > 2° > 1° ease (carbocation stability).
• Mechanism = E1 (stepwise):
  1. Protonate OH → alkyloxonium.
  2. \ce{H2O} leaves → carbocation.
  3. Base (often \ce{H2O}) removes β-H → alkene + \ce{H3O^+} (catalyst regenerated).
• Rearrangements common:
  • 1,2-alkyl shift or 1,2-hydride shift to form more stable C$^+$.
  • Example: 3,3-dimethyl-2-butanol → tertiary C$^+$ rearranged → major $\text{2,3-dimethyl-2-butene}$ (Zaitsev) & minor $\text{2,3-dimethyl-1-butene}$.

Electrophilic & Other Reactions of Alkenes

• Characteristic reaction = ADDITION (break $\pi$, form two $\sigma$ bonds).
• Alkene acts as nucleophile (e⁻ rich); reagent is electrophile.

1. Hydrohalogenation (HX)

• Two-step electrophilic addition:
  1. $\pi$ electrons → H–X; formation of C$^+$.
  2. X⁻ attacks carbocation.
• On unsymmetrical alkenes, obeys Markovnikov’s rule:
  • H attaches to C bearing more H, X to more substituted C.
  • Restated: pathway proceeds through the more substituted (more stable) carbocation.
• Radical variant (HBr + ROOR): anti-Markovnikov (peroxide effect).
  • Initiation: \ce{ROOR -> 2 RO^.}; chain with Br· radicals; no carbocation.

2. Acid-Catalyzed Hydration (H₂O, \ce{H^+})

• Follows Markovnikov; mechanism parallels HX addition (C$^+$ intermediate).
• Rearrangements possible (1,2-shift) → reliability issue.

3. Halogenation (X₂)

• Inert solvent (CCl₄): anti-addition via cyclic halonium ion.
  • Stereochemistry: trans-dihalide or anti-vicinal positions in acyclic substrates.
• Aqueous solvent → halohydrin formation.
  • H₂O opens halonium at more substituted C (Markovnikov orientation) → $\text{X–CH₂–CH(OH)–R}$.

4. Catalytic Hydrogenation (H₂/Pd-C, PtO₂, Ra-Ni)

• H₋H bonds dissociate on metal; alkene adsorbs; two H add syn to same face → alkane.
• Heterogeneous; useful for stereospecific reductions (cis addition across double bond).

5. Hydroboration–Oxidation

• Step 1 (BH₃·THF): syn, concerted addition; B on less substituted C, H on more substituted C (anti-Markovnikov).
• Step 2: \ce{H2O2/HO^-} → \ce{R–CH2–CH2–OH} + \ce{B(OH)_3}.
• No rearrangements; stereospecific syn addition.

6. Oxymercuration–Demercuration

• Step 1: \ce{Hg(OAc)_2, H2O} (THF) → mercurinium ion; water opens at more substituted C (Markovnikov).
• Step 2: \ce{NaBH4} replaces \ce{Hg^{2+}} with H.
• Produces Markovnikov alcohol without carbocation and rearrangements.

7. Epoxidation (peracids)

• Reagent: $\text{m-chloroperoxybenzoic acid (MCPBA)}$, \ce{RCO_3H}.
• Concerted syn transfer of O → epoxide keeps alkene stereochemistry (cis → cis epoxide, trans → trans epoxide).

Oxidation Reactions of Alkenes

1. Syn-Dihydroxylation

• OsO₄/\ce{NaHSO3,H2O} or cold \ce{KMnO4} (pH > 8).
• Concerted [3+2] cycloaddition → cyclic osmate/manganate ester → syn-vicinal diol (glycol).
• KMnO₄ is harsher; yields often lower due to over-oxidation.

2. Oxidative Cleavage

• Ozonolysis: \ce{O3} (–78 $^\circ$C) → molozonide → ozonide → reductive work-up (Me₂S or \ce{Zn/CH_3COOH}) → carbonyls.
  • General: \ce{R^1CH=CHR^2 -> R^1C(=O) + R^2C(=O)}.
• Hot basic KMnO₄ also cleaves:
  • $\text{\$0\degree\$}$ unsubstituted C → \ce{CO2 + H2O}.
  • Monosubstituted C → carboxylic acid.
  • Disubstituted C → ketone.

3. Epoxidation (see above) – classified as oxidation due to transfer of an O atom.

Radical Addition of HBr (Peroxide Effect)

• Preconditions: HBr + organic peroxide \ce{ROOR}.
• Chain mechanism (radical): Br· adds first → radical most stable at more substituted C → product shows anti-Markovnikov orientation.
• Works only for HBr (HI too slow; HCl endothermic).

Reaction Selectivity & Regio/Stereochemistry Summary

• Zaitsev vs Hofmann: elimination gives more substituted vs less substituted alkene; bases, steric bulk, or leaving-group nature can shift distribution.
• Markovnikov: electrophilic additions involve C$^+$ or bridged ion; nucleophile ends on more substituted carbon.
• Anti-Markovnikov: hydroboration-oxidation (via concerted mechanism) & radical HBr addition.
• Syn additions: catalytic hydrogenation, hydroboration, OsO₄/KMnO₄ dihydroxylation, epoxidation (overall) although epoxide opening can vary later.
• Anti additions: X₂ in inert solvents (trans products), halohydrin formation (X/OH anti), E2 eliminations due to anti-periplanar geometry.

Worked Examples Highlighted in Transcript

• \ce{Br–CH2CH2Br + Zn \xrightarrow{CH3COOH} CH2=CH2 + ZnBr2}
• \ce{(CH3)3C–Br \xrightarrow{t-BuOK/t-BuOH, \Delta} (CH3)2C=CH_2} (major Hoffmann from bulky base)
• \ce{CH3CH2CH=CH2 + HBr -> CH3CH2CHBrCH3} (Markovnikov)
• \ce{CH3CH2CH=CH2 + HBr/ROOR -> CH3CH2CH2CH_2Br} (anti-Markovnikov)
• \ce{Cyclohexene + Br2/CCl4 -> trans-1,2-dibromocyclohexane}
• \ce{Cyclohexene + Br2/H2O -> trans-2-bromocyclohexanol} (halohydrin)
• \ce{CH3CH=CH2 + BH3·THF; H2O2,OH^- -> CH3CH2CH2OH} (anti-Markovnikov alcohol)
• Comparative hydration routes for the same alkene:
  • Acid-catalyzed: risk of rearrangement.
  • Oxymercuration: Markovnikov, no rearrangement.
  • Hydroboration: anti-Markovnikov, syn.

Practical / Conceptual Connections & Implications

• Stability order of alkene: \text{tetra} > \text{tri} > \text{di} > \text{mono} > \text{ethylene} due to hyperconjugation & inductive effects.
• Carbocation rearrangements reflect driving force toward greater stability; safeguard needed (oxymercuration vs direct hydration).
• Diagnostic color tests: cold \ce{KMnO4} (Baeyer test) – disappearance of purple \ce{MnO4^-} → diol formation / green solution.
• Environmental & safety: OsO₄ is highly toxic/volatile; catalytic amounts often used with \ce{NMO} or \ce{tBuOOH} as re-oxidants.
• Industrial hydrogenation (e.g., margarine production) uses Ni catalysts; stereochemical outcome (cis vs trans fats) is nutritionally relevant.
• Synthetic planning: choice of addition/elimination conditions allows precise control of regiochemistry & stereochemistry without protecting groups.

Numerical / Statistical Details

• Relative rates of alcohol dehydration: \text{3° : 2° : 1° \approx 1 : 10^{-1} : 10^{-4}} (order-of-magnitude illustration of carbocation stability effect).
• Reaction temperature guidelines:
  • Cold \ce{KMnO_4} dihydroxylation: $\le 0\,^{\circ}!\text{C}$.
  • Ozonolysis bubbling: $-78\,^{\circ}!\text{C}$ (dry-ice/acetone bath).

Ethical & Safety Notes

• Use of heavy-metal oxidants (OsO₄, Hg(OAc)₂) demands strict handling & disposal protocols due to toxicity.
• Radical initiators (peroxides) are shock-/heat-sensitive; store cold and away from reductants.
• Industrial hydrogenation’s creation of trans-fats poses cardiovascular health concerns, illustrating societal impact of reaction conditions.