Reaction 1. Electrophilic addition of hydrogen halides (HX) to alkenes.

Reagents and conditions

Mechanistic details

· HCl, HBr in ether

· KI + H₃PO₄

· room temperature

· electrophilic addition

· carbocation intermediates

· Markovnikovs rule apply

· carbocation rearrangements possible

· no relative stereochemical preference

Reaction 2. Radical addition of hydrogen bromide (HBr) to alkenes. (NOT COVERED THIS TIME)

Reagents and conditions

Mechanistic details

· radical initiators (usually peroxides)

· heat or light

· chain reaction

· radical intermediates

· anti-Markovnikovs products

· no relative stereochemical preference

Reaction 3. Electrophilic addition of halogens (X₂) to alkenes.

Reagents and conditions

Mechanistic details

· Br₂, Cl₂ (or I₂) in CH₂Cl₂ or CCl₄

· room temperature

· electrophilic addition

· bromonium or chloronium ion intermediates

· anti addition

Reaction 4. Electrophilic addition of halogens to alkenes in the presence of water.

Reagents and conditions

Mechanistic details

· Br₂ or Cl₂ in H₂O or NBS in H₂O/DMSO

· room temperature

· electrophilic addition of X₂

· bromonium or chloronium ion intercepted by H₂O

· Markovnikovs rule apply (with respect to H₂O)

· anti addition

Reaction 5. Electrophilic addition of water to alkenes.

Reagents and conditions

Mechanistic details

· acid catalyst needed with non-nucleophilic counter ion (H₂SO₄, HClO_4, H₃PO₄)

· high temperature required

· often reversible (rather used to make alkenes from alcohols)

· electrophilic addition

· carbocations intermediates

· Markovnikovs rule applies

· no relative stereochemical preference

Reaction 6. Oxymercuration of alkenes (formal addition of water).

Reagents and conditions

Mechanistic details

· Hg(OAc)₂ in H₂O (or THF/H₂O)

· reduction step required to replace mercury with hydrogen (NaBH₄)

· room temperature

· electrophilic addition of mercury compound

· mercurinium ion as the intermediate intercepted by H₂O

· Markovnikovs rule applies with respect to H₂O

· reduction step with a complicated mechanism

· the addition of H₂O is anti, but reduction scrambles the stereochemistry (i.e. no relative stereochemical preference is observed)

Reaction 7. Hydroboration of alkenes (formal addition of water).

Reagents and conditions

Mechanistic details

· BH₃-THF complex in THF

· tri-fold addition (to borane) is common, giving trialkylboranes (R₃B)

· oxidation step necessary (H₂O₂/⁻OH)

· room temperature or heat

· electrophilic addition of BH₃

· cyclic transition state, putting boron at the least substituted carbon of the double bond

· syn addition, preserved in the oxidation step (stereospecific replacement of BR₂ with OH))

· anti-Markovnikov alcohols

Reaction 8. Hydrogenation of alkenes.

Reagents and conditions

Mechanistic details

· H₂ gas over heterogeneous catalysts (Pd/C, Pt, PtO₂)

· room temperature

· very facile reaction (many other functional groups remain untouched)

· surface reaction

· syn addition from the less crowded face

· mechanism is complicated

· redox reaction

Reaction 9. Hydroxylation of alkenes.

Reagents and conditions

Mechanistic details

· KMnO₄/⁻OH (lower yield)

· OsO₄/pyridine (higher yield but toxic and expensive)

· catalytic OsO₄ with NMO

· cyclic transition state and intermediate resulting in syn addition

· redox reaction

Reaction 10. Ozonolysis of alkenes.

Reagents and conditions

Mechanistic details

· ozone at low temperature followed by reduction with Zn/AcOH

· complicated mechanism with O₃

· oxidation followed by (partial) reduction

Reaction 11. Oxidation of diols.

Reagents and conditions

Mechanistic details

· 1,2-diol treated by HIO₄ in H₂O/THF

· equivalent to ozonolysis of the corresponding alkene

· cyclic intermediate with HIO₄

Reaction 12. Oxidation of alkenes with permanganate under acidic conditions.

Reagents and conditions

Mechanistic details

· potassium permanganate under acidic or neutral conditions

· redox reaction

· oxygen inserts into all former vinylic C-H bonds

Reaction 13. Electrophilic addition of hydrogen halides (HX) to alkynes.

Reagents and conditions

Mechanistic details

· HCl, HBr in acetic acid

· electrophilic addition

· vinyl carbocation as an intermediate

· Markovnikovs rule apply

· first addition usually trans

· second addition often follows

· less reactive than alkenes

Reaction 14. Electrophilic addition of halogens (X₂) to alkynes.

Reagents and conditions

Mechanistic details

· Cl₂, Br₂ in CCl₄

· electrophilic addition

· Markovnikovs rule apply

· first addition usually trans (anti) as if the halonium ion was an intermediate (but most likely it is not)

· second addition often follows

· less reactive than alkenes

Reaction 15. Electrophilic addition of water to alkynes.

Reagents and conditions

Mechanistic details

· HgSO₄/H₂O/H₂SO₄

· no NaBH₄ necessary to replace mercury (Hg) with hydrogen

· electrophilic addition catalyzed by Hg²⁺ (mercurinium ion not involved)

· Markovnikovs rule apply

· the primary product is an enol, a less stable tautomer of a ketone

Reaction 16. Hydroboration of alkynes (formal addition of water).

Reagents and conditions

Mechanistic details

· BH₃/THF gives mixture of regioisomers for disubstituted alkynes, double addition with terminal alkynes

· R₂BH (R = 1,2-dimethylpropyl) may be used for monoaddition to terminal alkynes

· four - membered cyclic transition state for addition

· syn addition

Reaction 17. Hydrogenation of alkynes.

Reagents and conditions

Mechanistic details

· Lindlar catalyst used for cis product (Pd, CaCO₃, Pb(OAc)₂, quinoline)

· lithium metal in ammonia for trans product

· hydrogenation is a heterogeneous reaction

· hydrogenation catalyst is poisoned (deactivated) to prevent further reduction of the double bond

· Li reduction involves electron - transfer process and proceeds via an intermediate vinylic carbanion

Reaction 18. Alkylation of acetylide anion.

Reagents and conditions

Mechanistic details

· KNH₂ or NaNH₂ used as a base (in NH₃ or THF)

· LDA in THF used as a base

· primary electrophiles (alkylating agents) work well

· the increased acidity of the sp hybridized carbon makes carbanion accessible (the lone electron pair in the conjugate base, acetylide anion, has large s character)

· S_N2 substitution mechanism followed (back-side attack on the electrophilic carbon)

Reaction 19. Oxidative cleavage of alkynes.

Reagents and conditions

Mechanistic details

· KMnO₄ or ozone

· often low yields

· complicated oxidation mechanisms

· more difficult to oxidize than alkenes

· substituted "ends" yield the corresponding carboxylic acids, unsubstituted ones give CO₂

Reaction 20. Electrophilic addition of HX to conjugated dienes.

Reagents and conditions

Mechanistic details

· HCl or HBr in ether

· electrophilic addition leading to allyl (resonance stabilized) carbocations

· the allyl cation can be attacked by the bromide anion at two positions

· the 1,2-adduct (A) is kinetically favored (predominates at low temperatures)

· the 1,4-adduct (B) is thermodynamically more stable and it predominates at higher temperatures

Reaction 21. Electrophilic addition of halogens to conjugated dienes.

Reagents and conditions

Mechanistic details

· Br₂ or Cl₂ in CCl₄ or CH₂Cl₂

· electrophilic addition leading to allyl (resonance stabilized) carbocations

· the allyl cation can be attacked by the bromide anion at two positions

· the 1,2-adduct is kinetically favored (predominates at low temperatures)

· the 1,4-adduct is thermodynamically more stable and predominates at higher temperatures

Reaction 22. Radical (chain) halogenation of alkanes.

Reagents and conditions

Mechanistic details

· X₂; the reaction is explosive for F₂ and very sluggish for I₂ (thermodynamic reasons)

· heat or light used to generate radicals in the initiation steps

· mixtures of products are obtained (mono- and poly-halogenated compounds, and different regioisomers)

· NBS in CCl₄ (with light or initiators) used for allylic or benzylic brominations

· radical chain reactions

· the initiation step generates X? radical

· selectivity is established in the hydrogen-abstraction step by X?

· the more reactive X?, the less selective it is

Reaction 23. Conversion of alcohols into alkyl halides.

Reagents and conditions

Mechanistic details

· HX in ether (works best for tertiary alcohols)

· PBr₃ in ether or CH₂Cl₂

· SOCl₂ in pyridine

· TosCl/pyridine followed by X⁻

· S_N1 mechanism for tertiary alcohols

· S_N2 mechanism for primary alcohols

· hydroxyl group is converted to a better leaving group by reaction with the reagent of choice

Reaction 24. Nucleophilic substitution reaction on sp³ hybridized carbons.

Reagents and conditions

Mechanistic details

· variety of conditions and solvents usually polar and protic solvents for SN1 reactions

· usually polar aprotic solvents for SN2 reactions

· S_N1 mechanism for tertiary substrates: the leaving group departs in a unimolecular rate-limiting step, generating the carbocation, which in the second step reacts with the nucleophile; ion pairs may be involved and carbocation rearrangements may compete

· S_N2 mechanism for primary substrates: the nucleophile displaces the leaving group in one-step bimolecular back-side attack leading to inversion of configuration on stereogenic centers

· secondary, allylic or benzylic substrates may react by both mechanisms

· competition with elimination reactions (E1 and E2) often observed

Reaction 25. Elimination reaction to form carbon-carbon double bonds.

Reagents and conditions

Mechanistic details

· variety of conditions and solvents

· usually strong bases favor E2 mechanism

· E1 mechanism for tertiary or secondary allylic or benzylic substrates: the leaving group departs in a unimolecular rate-limiting step, generating the carbocation, which in the second step is deprotonated (with base) on the carbon adjacent to the cationc center, yielding the olefin; carbocation rearrangements may compete

· E2 mechanism favored by strong bases: the base removes a proton from the carbon adjacent to one bearing the leaving group in a one-step bimolecular reaction that requires periplanar orientation of the hydrogen and the leaving group (anti-periplanar preferred)

· competition with substitution reactions (S_N1and S_N2) often observed

· Usually the most substituted olefin is the major product (Zaitsevs rule)

Reaction 26. Aromatic electrophilic substitution.

Reagents and conditions

Mechanistic details

· Br₂ and FeBr₃ (or AlBr₃) for bromination

· Cl₂ and FeCl₃ (or AlCl₃) for chlorination

· I₂ and H₂O₂ (or CuCl₂) for iodination

· HNO₃/H₂SO₄ for nitration

· SO₃/H₂SO₄ for sulfonation

· RX and AlCl₃ for alkylation

· RCOX and AlCl₃ for acylation

· positively charged electrophile adds to the aromatic ring in the rate-limiting step; the resulting carbocation reverts to aromaticity by the loss of proton

· the relative reactivity and regiochemistry of the reaction on substituted benzene derivatives is governed by the nature of the substituent: the substituents that are electron withdrawing by inductive and resonance effects are deactivating and meta-directing; the substituents that are electron withdrawing by inductive effects and electron donating by resonance are ortho- and para-directing and depending on the electron-density balance are deactivating (halides) or activating (O in ethers, N in amines or amides); the substituents that are electron donating by inductive and resonance (hyperconjugation) effects are activating and ortho- and para-directing

Reaction 27. Oxidation of side chains in aromatic compounds.

Reaction 28. Hydrogenation of aromatic compounds.