Difficulty: Intermediate | Prerequisites: Acids, bases, nucleophiles and carbocation stability (see companion notes).
This set of notes covers the major reaction types you will encounter in Organic Chemistry II: alkene additions, nucleophilic substitutions, eliminations, oxidations, Grignard reactions, esterification and electrophilic aromatic substitution. Each reaction is driven by the stability and reactivity principles from the companion notes on acids, bases and carbocations. Mastering the mechanism of each reaction, rather than memorising products alone, is the fastest route to handling novel exam problems. If terms like "Markovnikov" or "anti-periplanar" are unfamiliar, read through the key terms below before diving into the core content.
Alkenes react with electrophiles through addition mechanisms that follow Markovnikov's rule (unless radicals are involved). Substitution (SN1/SN2) and elimination (E1/E2) compete depending on the nucleophile, base and substrate. Alcohol oxidations, Grignard additions, Fischer esterification and electrophilic aromatic substitution on benzene round out the essential reaction toolkit for the ACS exam.
Markovnikov's rule
In the addition of HX to an alkene, the hydrogen adds to the carbon with more hydrogens (less substituted), and the halide adds to the more substituted carbon. In simple terms, the rich get richer: the carbon that already has more substituents gets the new group, because that path goes through the more stable carbocation.
Anti-Markovnikov addition
The opposite regiochemistry: the hydrogen ends up on the more substituted carbon. This occurs in radical additions (HBr with peroxides, ROOR).
Bromonium ion
A three-membered ring intermediate formed when Br₂ adds across a double bond. The ring blocks one face of the molecule, forcing the nucleophile to attack from the opposite side (anti addition).
Anti addition
The two new groups add to opposite faces of the double bond. Halogenation of alkenes proceeds through anti addition via the bromonium ion.
Backside attack
In SN2, the nucleophile attacks the electrophilic carbon from the side opposite the leaving group, resulting in inversion of stereochemistry (like an umbrella flipping inside out).
Zaitsev's rule
In elimination reactions, the more substituted alkene (more stable) is the major product, unless a bulky base forces the less substituted (Hofmann) product.
Anti-periplanar geometry
In E2 elimination, the leaving group and the proton being removed must be on opposite sides of the C-C bond (180° dihedral angle). This is a strict geometric requirement.
Grignard reagent
An organomagnesium halide (RMgBr or RMgCl) that acts as a strong nucleophilic carbon. It adds to carbonyl compounds to form new C-C bonds.
Electrophilic aromatic substitution (EAS)
A reaction in which an electrophile replaces a hydrogen on an aromatic ring. The ring's aromaticity is preserved because substitution, not addition, occurs.
Addition of HX (HCl, HBr, HI)
Alkene + HX forms a carbocation intermediate, then the halide attacks. Product follows Markovnikov's rule: X ends up on the more substituted carbon.
Mechanism: protonation of the alkene (forming the more stable carbocation), then nucleophilic attack by X⁻.
Carbocation rearrangements can occur if a more stable cation is accessible by a hydride or methyl shift.
Addition of HBr with peroxides (ROOR)
Radical mechanism reverses the regiochemistry: anti-Markovnikov addition. Br ends up on the less substituted carbon.
Only works with HBr (not HCl or HI). The radical chain is: initiation (peroxide homolysis), propagation (Br radical adds to the less substituted carbon to form the more stable radical), termination.
Halogenation (Br₂ or Cl₂)
Alkene + Br₂ forms a bromonium ion intermediate. The second bromide attacks from the opposite face: anti addition, giving a trans-dihalide.
Stereochemistry: anti addition is the key feature. Both halogens add, but from opposite faces.
Halohydrin formation (Br₂/H₂O)
Same bromonium ion intermediate, but water acts as the nucleophile instead of Br⁻. Water attacks the more substituted carbon (the more electrophilic carbon of the bromonium ion). Product: OH on the more substituted carbon, Br on the less substituted carbon. Anti addition.
Acid-catalysed hydration (H₂SO₄/H₂O)
Alkene + H₂SO₄/H₂O forms a carbocation, then water attacks. Product: Markovnikov alcohol. Rearrangements possible.
Hydrogenation (H₂/Pd)
Alkene + H₂ over a metal catalyst (Pd, Pt or Ni) gives an alkane. Syn addition of both hydrogens to the same face. This is a reduction.
SN2 (bimolecular nucleophilic substitution)
One concerted step: the nucleophile attacks as the leaving group departs.
Backside attack leads to inversion of configuration (Walden inversion).
Rate = k[substrate][nucleophile]. Both species are in the rate-determining step.
Favoured at 1° (and methyl) carbons where steric hindrance is low.
Best with strong, unhindered nucleophiles and polar aprotic solvents (DMSO, DMF, acetone).
SN1 (unimolecular nucleophilic substitution)
Two steps: (1) the leaving group departs to form a carbocation, (2) the nucleophile attacks the carbocation.
Rate = k[substrate]. Only the substrate is in the rate-determining step.
Favoured at 3° carbons, where the carbocation is most stable. Benzylic and allylic substrates also work.
Produces a racemic mixture (the nucleophile can attack from either face of the planar carbocation).
Carbocation rearrangements are possible.
Best with weak nucleophiles and polar protic solvents (water, alcohols).
E2 (bimolecular elimination)
One concerted step: a strong base abstracts a proton while the leaving group departs simultaneously.
Requires anti-periplanar geometry: the H and the leaving group must be on opposite sides of the C-C bond (180° dihedral).
Produces the Zaitsev alkene (more substituted, more stable) as the major product, unless a bulky base forces the Hofmann product.
Rate = k[substrate][base].
Favoured by strong, bulky bases (t-BuO⁻, LDA) and higher temperatures.
E1 (unimolecular elimination)
Two steps: (1) the leaving group departs to form a carbocation, (2) a base removes a proton from the carbon adjacent to the cation, forming the alkene.
Same carbocation intermediate as SN1, so E1 and SN1 often compete.
Zaitsev product is the major alkene.
Rate = k[substrate].
Favoured at 3° substrates and at elevated temperatures. Heat generally shifts the SN1/E1 competition towards elimination.
The product of oxidation depends on the alcohol's degree and the reagent used.
PCC (pyridinium chlorochromate) – a mild, selective oxidant.
1° alcohol → aldehyde (stops here, does not over-oxidise to carboxylic acid).
2° alcohol → ketone.
3° alcohol → no reaction (no H on the carbon bearing the OH).
Jones reagent (CrO₃/H₂SO₄/H₂O) – a stronger oxidant in aqueous acidic conditions.
1° alcohol → carboxylic acid (goes all the way through the aldehyde).
2° alcohol → ketone.
3° alcohol → no reaction.
The choice of reagent is how you control whether a primary alcohol stops at the aldehyde or continues to the acid. PCC stops at aldehyde; Jones (or KMnO₄, Na₂Cr₂O₇) pushes to acid.
A Grignard reagent (RMgBr) is a powerful carbon nucleophile. It attacks the electrophilic carbon of a carbonyl group, forming a new C-C bond.
General sequence:
RMgBr attacks the carbonyl carbon of an aldehyde, ketone, ester or CO₂.
The magnesium alkoxide intermediate is formed.
Aqueous acid workup (H₃O⁺) protonates the alkoxide to give the alcohol.
Products by carbonyl type:
Formaldehyde (H₂C=O) + RMgBr → 1° alcohol.
Aldehyde (RCHO) + R'MgBr → 2° alcohol.
Ketone (RCOR') + R''MgBr → 3° alcohol.
CO₂ + RMgBr → carboxylic acid (after H₃O⁺ workup).
Ester + 2 equivalents of RMgBr → 3° alcohol (two additions).
Grignard reagents are extremely sensitive to protic solvents and water. The reaction must be run under anhydrous conditions in an ether solvent (diethyl ether or THF).
Acid + alcohol in the presence of an acid catalyst (H⁺) gives an ester + water.
RCOOH + R'OH ⇌ RCOOR' + H₂O
This is an equilibrium reaction. To push it towards the ester product, use excess alcohol or remove water (Le Chatelier's principle).
The mechanism proceeds through nucleophilic addition of the alcohol to the protonated carboxylic acid, followed by loss of water. It is the reverse of acid-catalysed ester hydrolysis.
Benzene undergoes substitution rather than addition to preserve its aromaticity. An electrophile replaces one hydrogen on the ring.
Common EAS reactions and the electrophile generated:
Bromination: Br₂ + FeBr₃ (Lewis acid catalyst) generates Br⁺. Product: bromobenzene.
Nitration: HNO₃ + H₂SO₄ generates NO₂⁺ (nitronium ion). Product: nitrobenzene.
Friedel-Crafts alkylation: R-Cl + AlCl₃ generates R⁺ (or equivalent complex). Product: alkylbenzene. Susceptible to carbocation rearrangements and polyalkylation.
Friedel-Crafts acylation: RCOCl + AlCl₃ generates RCO⁺ (acylium ion). Product: aryl ketone. No rearrangement, no polyacylation (the product is deactivated).
Directing effects of substituents:
Ortho/para directors – electron-donating groups (OH, NH₂, OR, alkyl) and halogens. They activate the ring (except halogens, which are deactivating but still direct ortho/para).
Meta directors – electron-withdrawing groups (NO₂, CN, COOH, COR, SO₃H). They deactivate the ring and steer incoming electrophiles to the meta position.
Alkene + HX → Markovnikov addition (carbocation intermediate) Alkene + HBr/ROOR → anti-Markovnikov addition (radical intermediate) Alkene + Br₂ → anti addition via bromonium ion → trans-dihalide Alkene + Br₂/H₂O → halohydrin (OH on more substituted C, anti addition) Alkene + H₂SO₄/H₂O → Markovnikov alcohol (carbocation intermediate) Alkene + H₂/Pd → alkane (syn addition)
RX + strong Nu⁻ → SN2 (inversion, 1° favoured) RX (3°) + weak Nu → SN1 (racemisation, carbocation intermediate) RX + strong base → E2 (anti-periplanar, Zaitsev alkene) RX (3°) + heat → E1 (carbocation, Zaitsev alkene)
1° alcohol + PCC → aldehyde 1° alcohol + Jones → carboxylic acid 2° alcohol + PCC or Jones → ketone
RMgBr + carbonyl → alcohol (after H₃O⁺) RCOOH + R'OH + H⁺ ⇌ ester + H₂O
Benzene + E⁺ (via Lewis acid) → substitution product (o/p or meta depending on existing substituents)
Friedel-Crafts acylation is a foundational step in pharmaceutical synthesis: ibuprofen and naproxen are both built on acylated aromatic rings.
Fischer esterification is how flavour and fragrance esters (banana, pineapple, wintergreen) are made industrially, and it is the reverse of the hydrolysis that digests fats in your body.
Grignard reactions remain one of the most widely used methods for forming carbon-carbon bonds in both academic labs and industrial process chemistry.
Students often assume anti-Markovnikov addition happens with all hydrogen halides. It only occurs with HBr in the presence of peroxides (radical conditions). HCl and HI do not undergo useful radical additions.
Students frequently forget the stereochemistry of SN2: it always inverts. If you start with R, you get S (assuming no priority change). Forgetting inversion is one of the most common mistakes on the ACS exam.
Students sometimes confuse which oxidant stops at aldehyde. PCC is the mild one that stops. Jones, KMnO₄ and chromic acid all push primary alcohols to carboxylic acids.
Students often think Friedel-Crafts alkylation is straightforward, but it suffers from two problems: carbocation rearrangements (the electrophile can rearrange before attacking the ring) and polyalkylation (the product is more reactive than benzene). Friedel-Crafts acylation avoids both.
⚠️ The SN1/SN2/E1/E2 decision question appears on virtually every ACS organic exam. Practise: given a substrate, nucleophile/base, solvent and temperature, name the dominant pathway and predict the product with correct stereochemistry.
⚠️ Markovnikov vs anti-Markovnikov regiochemistry is a standard multiple-choice item. Remember: peroxides flip HBr only.
⚠️ Knowing the difference between PCC and Jones oxidation for primary alcohols is tested directly. A question may give you a primary alcohol and two reagents and ask which product forms with each.
⚠️ Directing effects in EAS (ortho/para vs meta) are heavily tested. Be able to predict the major product when a substituted benzene undergoes bromination, nitration or Friedel-Crafts.
True or false: HBr with peroxides adds to an alkene with Markovnikov regiochemistry. (False, it gives anti-Markovnikov.)
Fill in the blank: SN2 reactions proceed with ______ of configuration at the stereocentre. (Inversion)
True or false: E2 elimination requires the H and leaving group to be syn-periplanar. (False, they must be anti-periplanar.)
Fill in the blank: PCC oxidises a primary alcohol to a(n) ______, while Jones reagent oxidises it to a(n) ______. (Aldehyde; carboxylic acid)
True or false: A nitro group (NO₂) on benzene directs incoming electrophiles to the ortho and para positions. (False, NO₂ is a meta director.)
Q: 2-butene is treated with HBr. Draw or name the major product and state the rule that predicts it.
A: 2-bromobutane. Both carbons of the double bond are equally substituted, so both possible carbocations are secondary. The product is still governed by Markovnikov's rule, but in this symmetric case the same product forms either way.
Q: 1-bromopropane is treated with NaOH in DMSO. What is the major product and mechanism?
A: 1-propanol by SN2. NaOH is a strong nucleophile, the substrate is primary, and DMSO is a polar aprotic solvent. Backside attack gives inversion at the carbon bearing the bromine.
Q: 2-bromo-2-methylbutane is heated with ethanol. What products form and by which mechanisms?
A: A mixture of SN1 and E1 products. The substrate is tertiary, and ethanol is a weak nucleophile/base. SN1 gives an ether (ethyl 2-methyl-2-butyl ether); E1 gives the Zaitsev alkene (2-methyl-2-butene as the major alkene). Heat shifts the competition towards elimination.
Q: What product forms when 1-pentanol is treated with PCC? What about with Jones reagent?
A: PCC gives pentanal (the aldehyde). Jones reagent gives pentanoic acid (the carboxylic acid).
Q: Toluene (methylbenzene) is treated with Br₂/FeBr₃. Where does the bromine go?
A: Ortho and para to the methyl group. Methyl is an electron-donating group (alkyl) and an ortho/para director. The para product usually predominates due to steric effects.
The SN1/SN2/E1/E2 framework draws directly on the acid-base and nucleophilicity concepts from the companion study notes. Carbocation stability, covered there, determines whether SN1/E1 pathways are accessible.
Alkene addition reactions produce the starting materials for many later chapters: alcohols (from hydration) feed into oxidation and esterification; alkyl halides (from HX addition) are the substrates for substitution and elimination.
EAS connects forward to multi-step synthesis problems where you need to plan the order of substituent additions to get the correct regiochemistry on a benzene ring.
Markovnikov, anti-Markovnikov, regioselectivity, radical addition, bromonium ion, anti addition, syn addition, hydrohalogenation, hydroboration, oxymercuration, carbocation rearrangement, SN1 mechanism, SN2 mechanism, Walden inversion, racemisation, E1 elimination, E2 elimination, Zaitsev rule, Hofmann product, anti-periplanar, PCC oxidation, Jones oxidation, chromium oxidation, Grignard reagent, organomagnesium, Fischer esterification, acid-catalysed ester, electrophilic aromatic substitution, EAS, Friedel-Crafts alkylation, Friedel-Crafts acylation, ortho para director, meta director, activating group, deactivating group, Lewis acid catalyst, nitronium ion, acylium ion