Organic Chemistry at Penn State: Reactions

Here is just a list of the reactions that we discussed in detail in class. We plan to add mechanistic schemes and other "goodies" slowly over the next few semesters. For now, just to help you keep track of the transformations we offer some limited "highlights". Please note that no stereochemistry is implied in the reaction schemes.

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 Markovnikov's 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-Markovnikov's 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 Markovnikov's 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 Markovnikov's 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 Markovnikov's 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 Markovnikov's 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 Markovnikov's 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) Markovnikov's 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 R'₂BH (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 halonium ion intermediate 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 (Zaitsev's 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 AlCl₃for 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.

Reagents and conditions	Mechanistic details
KMnO₄ or Na₂Cr₂O₇	complex oxidation mechanism requires at least one benzylic hydrogen

Reaction 28. Hydrogenation of aromatic compounds.

Reagents and conditions	Mechanistic details
H₂ (several hundred atm) over Pd H₂ (1 atm) over Rh	heterogeneous catalysis with a complex mechanism no partial reduction possible

Reaction 29. Reduction of carbonyl compounds to alcohols.

Reagents and conditions	Mechanistic details
NaBH₄ (or LiAlH₄) for aldehydes and ketones LiAlH₄ for carboxylic acids and esters BH₃-THF for carboxylic acids	the hydrides deliver H⁻ to the carbonyl-group carbon (nucleophilic addition to C-O double bond) for carboxylic acids and their derivatives, the tetrahedral intermediate formed loses R'O⁻ group, and the newly formed carbonyl group is reduced again

Reaction 30. Addition of Grignard reagents to carbonyl compounds to yield alcohols.

Reagents and conditions	Mechanistic details
Grignard reagents are prepared by reacting organic halides with metallic magnesium in ether solvents usually carried out in ether solvents (ether, THF) organolithium compounds (RLi) can be used instead of Grignard reagents	nucleophilic addition of electron-rich (carbanion-like) carbon from the organometallic reagent to the electrophilic carbon of the carbonyl group the addition to esters takes place twice; the initially formed tetrahedral intermediate expels RO⁻, regenerating the carbonyl group which reacts with the second molecule of the organometallic reagent

Reaction 31. Dehydration of alcohols.

Reagents and conditions	Mechanistic details
acid with a non-nucleophilic counterion (H₂SO₄) for tertiary substrates POCl₃/pyridine for 2^o and 1^o alcohols	E1 mechanism for tertiary alcohols E2 mechanism for POCl₃/pyridine (POCl₃ converts -OH into a good leaving group: -OPOCl₂) usually Zaitsev's rule followed (see Reaction 25)

Reaction 32. Oxidation of alcohols.

Reagents and conditions	Mechanistic details
PCC (pyridinium chlorochromate) or periodinane for oxidation of 1^o alcohols to aldehydes (2^o alcohols are oxidized to ketones) Jones' reagent (CrO₃/H₂SO₄/H₂O/acetone) or dichromate (Na₂Cr₂O₇) for oxidation of 1^o alcohols to carboxylic acids and 2^o alcohols to ketones	E2-like elimination on chromate or periodinane intermediates

Reaction 33. The Williamson ether synthesis.

Reagents and conditions	Mechanistic details
alkoxides are prepared by reaction of alcohols with bases or alkali metals reaction of alkoxides with primary alkyl halides intramolecular reaction yields cyclic ethers	S_N2 substitution reaction with oxygen serving as nucleophile

Reaction 34. Acidic cleavage of ethers.

Reagents and conditions	Mechanistic details
HI or HBr for 1^o and 2^o ethers HI, HBr and HCl for 3^oethers	S_N2 for primary ethers (after protonation on oxygen, attack by X⁻ on the least substituted of the two carbons) S_N1 for tertiary, benzylic or allylic ethers (after protonation on oxygen)

Reaction 35. Synthesis of epoxides with peroxyacids.

Reagents and conditions	Mechanistic details
peroxyacids (RCOOOH, for example m-chloroperoxybenzoic acid, MCPBA)	direct oxygen transfer from the peroxyacid to the alkene (syn stereochemistry)

Reaction 36. Ring-opening reactions of epoxides.

Reagents and conditions	Mechanistic details
acid catalysis (H₂O, Cl⁻, Br⁻, I⁻ as nucleophiles) direct nucleophile addition (HO⁻, RO⁻, RNH₂, R₂N⁻, RMgX)	under acid catalyzed conditions the protonated epoxide can be attacked by the nucleophile at the more (usually the major site of attack), or the less substituted site, depending on substitution patterns (anti stereochemistry results) direct nucleophilic attack (S_N2) takes place at the least substituted carbon (anti stereochemistry results)

Reactions

Last updated 08/07/12

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