Difficulty: Intermediate to Advanced | Prerequisites: Nomenclature and stereochemistry notes, Lewis structures, acid-base concepts.
This is the core of Organic Chemistry I: given a starting material and a set of reagents, what product forms, and why? The final exam tests this from three angles. First, matching reagents to transformations (a 24-point section). Second, predicting products with correct regiochemistry and stereochemistry (30 points). Third, drawing full arrow-pushing mechanisms (26 points). If nomenclature is the language, reactions are the grammar. You need to know the major reaction families (substitution, elimination, addition) and the conditions that favour each pathway.
Learn to recognise what each reagent set does (substitution, elimination, addition, oxidation, reduction, or rearrangement), predict products with correct regio- and stereochemistry, and draw arrow-pushing mechanisms step by step. The exam rewards pattern recognition: if you know the reagent, you know the transformation.
SN2 (bimolecular nucleophilic substitution)
A one-step mechanism where the nucleophile attacks the electrophilic carbon at the same time as the leaving group departs. Rate = k[substrate][nucleophile]. Inversion of configuration at the carbon.
In simple terms, the nucleophile shoves the leaving group out the back door in one concerted motion, flipping the stereocentre like an umbrella in the wind.
SN1 (unimolecular nucleophilic substitution)
A two-step mechanism: the leaving group departs first to form a carbocation, then the nucleophile attacks. Rate = k[substrate]. Produces a racemic mixture (or near-racemic) because the carbocation is planar.
Think of it as the leaving group walking away on its own, leaving a flat, open intermediate that can be attacked from either face.
E2 (bimolecular elimination)
A one-step mechanism where a strong base removes a beta-hydrogen at the same time as the leaving group departs, forming a double bond. Requires anti-periplanar geometry of the H and leaving group.
In simple terms, the base grabs a hydrogen and the leaving group exits simultaneously, zipping the two carbons together into a double bond.
E1 (unimolecular elimination)
A two-step mechanism: the leaving group departs to form a carbocation, then a base removes a beta-hydrogen to form the alkene. Follows Zaitsev's rule (most substituted alkene is the major product).
Markovnikov addition
In the addition of HX to an alkene, the hydrogen adds to the less substituted carbon and the X adds to the more substituted carbon. The rule follows from forming the more stable carbocation intermediate.
In simple terms, "the rich get richer": the carbon with more hydrogens gets the new hydrogen.
Anti-Markovnikov addition
The opposite regiochemistry: X ends up on the less substituted carbon. This happens with HBr in the presence of peroxides (ROOR), which triggers a radical mechanism.
Hydroboration-oxidation
A two-step sequence (BH₃, then H₂O₂/OH⁻) that adds water across a double bond with anti-Markovnikov regiochemistry and syn stereochemistry.
Epoxidation
Treatment of an alkene with a peroxy acid (e.g. mCPBA) to form a three-membered ring containing oxygen (an epoxide). The reaction is stereospecific: a cis alkene gives a cis epoxide.
Diels-Alder reaction
A [4+2] cycloaddition between a conjugated diene (4 pi electrons) and a dienophile (2 pi electrons) to form a six-membered ring. It is concerted, stereospecific (syn addition on both components), and favoured when the dienophile is electron-poor.
Tosylate (OTs)
A leaving group formed by treating an alcohol with TsCl (tosyl chloride) and pyridine. Converts the poor leaving group -OH into the excellent leaving group -OTs without changing the carbon skeleton or stereocentre configuration.
Think of it as giving the alcohol a disguise so it can participate in substitution and elimination reactions.
The practice final lists 17 reagent sets (A through Q). Below is a guide to what each one does and when to use it.
Reagent Set | What It Does |
|---|---|
A) SOCl₂, pyridine | Converts -OH to -Cl (with inversion). A way to turn an alcohol into an alkyl chloride. |
B) H₂, Pt | Catalytic hydrogenation: reduces alkenes and alkynes to alkanes (syn addition of H₂). |
C) Na, NH₃ | Dissolving metal reduction of an alkyne to a trans alkene (anti addition of H₂, Birch-type conditions). |
D) HOOC-C₆ring-COOH (a dicarboxylic acid) | A cis-dihydroxylation equivalent or a Diels-Alder diacid. Context-dependent. |
E) mCPBA | Epoxidation of an alkene to form an epoxide. Stereospecific (syn). |
F) HBr | Markovnikov addition of HBr to an alkene. H goes to the less substituted C, Br to the more substituted C. |
G) NaOCH₃ | Strong base / nucleophile in methanol. Promotes E2 elimination or SN2 substitution with methoxide. |
H) H₂, Lindlar catalyst | Partial reduction of an alkyne to a cis alkene (syn addition, stops at the double bond). |
I) Maleic anhydride (cis-butenedioic anhydride) | A classic Diels-Alder dienophile. |
J) TsCl, pyridine | Converts -OH to -OTs (tosylate). Makes the hydroxyl a good leaving group without changing stereochemistry at carbon. |
K) H₂SO₄, CH₃OH | Acid-catalysed addition of methanol to an alkene (Markovnikov), or Fischer esterification with a carboxylic acid. |
L) Br₂, heat | Allylic or benzylic bromination (radical conditions). |
M) NBS, hv | N-Bromosuccinimide with light: selective allylic or benzylic bromination via radical mechanism. |
N) HBr, ROOR, heat | Anti-Markovnikov addition of HBr via radical mechanism. Br goes to the less substituted carbon. |
O) H₃PO₄ | Acid catalyst for dehydration of alcohols to alkenes. E1 conditions, Zaitsev product. |
P) NaOH, H₂O | Basic aqueous conditions. Hydrolysis or SN2 with hydroxide as nucleophile. |
Q) KOC(CH₃)₃ (potassium tert-butoxide) | Bulky, strong, non-nucleophilic base. Strongly favours E2 elimination (Hofmann product with bulky base, or Zaitsev with less hindered substrates). |
Identify the functional group transformation: what group is present in the starting material, and what group appears in the product?
Classify the transformation type: substitution (one group replaces another), elimination (a double bond forms), addition (a double bond is consumed), oxidation, or reduction.
Match to the reagent set that performs that specific transformation with the correct regiochemistry and stereochemistry.
Each reagent is used only once, so cross off used answers as you go. Start with the ones you are most confident about.
Identify the substrate class: Is it an alcohol, alkyl halide, alkene, alkyne, or aromatic compound?
Identify the reagent type: Nucleophile, base, acid, oxidant, reductant, radical initiator?
Determine the reaction pathway: SN1, SN2, E1, E2, electrophilic addition, radical addition, pericyclic?
Apply regiochemistry rules: Markovnikov vs anti-Markovnikov, Zaitsev vs Hofmann.
Apply stereochemistry rules: Inversion (SN2), racemisation (SN1), syn addition (hydroboration, hydrogenation, epoxidation), anti addition (bromine, opening of bromonium ions), anti-periplanar requirement (E2).
Alcohol to tosylate, then nucleophilic substitution:
Starting material: a secondary alcohol. Step 1: TsCl, pyridine converts -OH to -OTs with retention of configuration. Step 2: NaCN performs an SN2 on the tosylate, displacing OTs with CN⁻ and inverting the stereocentre.
Alkene to anti-Markovnikov product (radical addition):
Starting material: an alkene. Reagent: HBr, ROOR, heat. The peroxide generates radicals. Br adds to the less substituted carbon (anti-Markovnikov). The product is a primary or less substituted bromide.
Dehydration followed by addition:
An alcohol treated with H₂SO₄/H₂O undergoes acid-catalysed dehydration to form the Zaitsev alkene (most substituted). That alkene can then react further if another reagent is present.
Hydroboration-oxidation:
BH₃ adds syn across the double bond with boron going to the less substituted carbon (anti-Markovnikov). 2) H₂O₂/OH⁻ replaces boron with -OH. Net result: anti-Markovnikov, syn addition of water.
Oxymercuration-type hydration:
H₂O, H₂SO₄, HgSO₄ on an alkyne gives Markovnikov addition of water, ultimately forming a ketone (via keto-enol tautomerism). On a terminal alkyne, the product is a methyl ketone.
Diels-Alder:
A conjugated diene reacts with an electron-poor dienophile in a [4+2] cycloaddition. The product is a cyclohexene. To work out diene and dienophile from a product, perform a retro Diels-Alder: break the bond between the two carbons that were newly formed and unfold the ring.
One step, concerted: nucleophile attacks the backside of the electrophilic carbon while the leaving group departs.
Energy diagram: single transition state, no intermediate.
Stereochemistry: complete inversion (Walden inversion).
Favoured by: strong nucleophile, primary or methyl substrate, polar aprotic solvent, good leaving group.
Two steps: (1) leaving group departs to form a carbocation, (2) nucleophile attacks the carbocation.
Energy diagram: two transition states with a carbocation intermediate between them.
Stereochemistry: racemisation (attack from both faces of the planar carbocation), sometimes with slight excess of inversion.
Favoured by: tertiary substrate (stable carbocation), weak nucleophile, polar protic solvent, good leaving group.
One step, concerted: a strong base removes a beta-hydrogen while the leaving group departs, forming a pi bond.
Requires anti-periplanar arrangement of the H and the leaving group.
Zaitsev's rule usually applies (most substituted alkene), but bulky bases (like KOC(CH₃)₃) can give the Hofmann (less substituted) product.
Favoured by: strong base, secondary or tertiary substrate, high temperature.
Two steps: (1) leaving group departs to form a carbocation, (2) base removes a beta-hydrogen to form the alkene.
Zaitsev product is major.
Often competes with SN1 under the same conditions. Higher temperature favours elimination over substitution.
Step 1: the pi electrons of the alkene attack the electrophile (H⁺), forming the more stable carbocation (Markovnikov).
Step 2: the nucleophile (X⁻ or H₂O) attacks the carbocation.
Stereochemistry: typically a mixture of syn and anti addition (the carbocation is planar).
Initiation: peroxide homolyses to give radicals; radical abstracts H from HBr to give Br radical.
Propagation step 1: Br radical adds to the less substituted carbon of the alkene (anti-Markovnikov), forming the more stable carbon radical.
Propagation step 2: carbon radical abstracts H from HBr, regenerating the Br radical.
Net result: anti-Markovnikov addition of HBr.
First equivalent of Br₂ adds across the triple bond via a bromonium-ion-like mechanism (or direct electrophilic addition) to give a dibromoalkene (typically trans for the first addition).
Second equivalent of Br₂ adds across the remaining double bond to give a tetrabromoalkane.
The mechanism proceeds through bromonium ion intermediates, with anti addition at each step.
Step 1: the -OH is protonated by HCl to make it a good leaving group (-OH₂⁺).
Step 2: the leaving group departs to form an allylic carbocation, which is resonance-stabilised (draw both resonance structures).
Step 3: Cl⁻ attacks the carbocation. If the allylic cation has two contributing structures, the product forms at the more substituted position (or the position shown in the product).
This is an SN1-like process. The allylic stabilisation of the carbocation is what makes it feasible.
SN1 vs SN2 decision factors:
Substrate: methyl/primary = SN2; tertiary = SN1; secondary = depends on nucleophile and solvent.
Nucleophile: strong = SN2; weak = SN1.
Solvent: polar aprotic = SN2; polar protic = SN1.
Leaving group: good leaving group needed for both.
E1 vs E2 decision factors:
Base: strong base = E2; weak or no base = E1.
Substrate: tertiary substrates undergo E2 with strong base, E1 with weak base. Primary substrates rarely undergo elimination unless a very strong, bulky base is used.
Temperature: high temperature favours elimination over substitution.
SN1 rate ranking:
Rate depends on carbocation stability: benzylic/allylic tertiary > tertiary > allylic/benzylic secondary > secondary > primary > methyl. The leaving group also matters: I⁻ > Br⁻ > Cl⁻ > F⁻ for alkyl halides.
Substitution and elimination reactions underpin a huge amount of industrial and pharmaceutical chemistry. The synthesis of ibuprofen, for example, involves an SN2 step. Radical reactions are how polyethylene and polypropylene plastics are manufactured. The Diels-Alder reaction is used to construct complex natural products in total synthesis, and it earned Otto Diels and Kurt Alder the Nobel Prize in Chemistry in 1950.
"HBr always gives Markovnikov addition." Only without peroxides. With ROOR (peroxide), HBr adds anti-Markovnikov via a radical pathway. This only works for HBr, not HCl or HI.
"E2 always gives the Zaitsev product." Not with a bulky base like KOC(CH₃)₃ (potassium tert-butoxide), which favours the less substituted (Hofmann) alkene because it cannot easily access the more hindered beta-hydrogen.
"SN1 and E1 cannot happen at the same time." They share the same first step (carbocation formation) and frequently compete. Temperature is the lever: higher temperature favours elimination.
"Carbocation rearrangements are rare." They are common whenever a less stable carbocation can become more stable by a 1,2-hydride or 1,2-methyl shift. Always check for rearrangement when drawing SN1 or E1 mechanisms.
⚠️ The reagent matching section (24 points) is essentially a vocabulary test. If you have memorised what each reagent set does, it is free points. Each reagent set is used only once.
⚠️ "Predict the product" (30 points) is the single largest section. You must show correct regiochemistry and stereochemistry. If enantiomers are formed, write "+ enantiomer."
⚠️ Mechanism questions (26 points) require every curved arrow, every intermediate, and resonance structures where relevant. Partial credit is possible, so draw what you know even if you are unsure about one step.
⚠️ The SN1 rate ranking question (part of the fill-in-the-blanks section) tests carbocation stability. Remember: benzylic and allylic carbocations are stabilised by resonance.
True or false: SN2 reactions proceed with retention of configuration. (False, they proceed with inversion.)
Fill in the blank: HBr + ROOR adds HBr to an alkene with ______ regiochemistry. (anti-Markovnikov)
True or false: E2 elimination requires the H and leaving group to be in a syn-periplanar arrangement. (False, anti-periplanar.)
Fill in the blank: Hydroboration-oxidation gives ______ addition with ______ regiochemistry. (syn, anti-Markovnikov)
True or false: A Diels-Alder reaction requires an electron-rich dienophile. (False, electron-poor dienophile.)
Q: An alcohol is treated with TsCl/pyridine, then NaCN. What is the overall transformation and what happens to the stereochemistry?
A: The alcohol is converted to a tosylate (retention at carbon), then CN⁻ performs an SN2 substitution (inversion). The net result is replacement of -OH with -CN with one inversion (overall inversion relative to the original alcohol).
Q: Draw the major product when 1-methylcyclohexene reacts with HBr.
A: Markovnikov addition. H adds to the less substituted carbon of the double bond (C2), Br adds to the more substituted carbon (C1, the one bearing the methyl). Product: 1-bromo-1-methylcyclohexane.
Q: What reagents convert a terminal alkyne into a cis alkene?
A: H₂ with Lindlar catalyst (poisoned palladium on CaCO₃). This performs a syn partial hydrogenation, stopping at the cis alkene.
Q: What reagents convert a terminal alkyne into a trans alkene?
A: Na, NH₃ (dissolving metal reduction). This gives anti addition of hydrogen, producing the trans alkene.
Q: Rank these substrates in order of increasing SN1 rate: a primary alkyl chloride, a secondary alkyl chloride, a tertiary alkyl chloride, a benzylic chloride.
A: Primary < secondary < tertiary < benzylic (assuming the benzylic is also secondary or tertiary). SN1 rate depends on carbocation stability, and benzylic carbocations are resonance-stabilised.
Q: Draw the complete mechanism for the reaction of an allylic alcohol with HCl to give an allylic chloride with rearrangement.
A: (1) Protonation of -OH by HCl to give -OH₂⁺. (2) Loss of water to form the allylic carbocation. (3) Draw the resonance structures of the allylic cation (the positive charge is delocalised over two carbons). (4) Cl⁻ attacks at the more substituted terminus of the allylic system.
Reaction mechanisms build directly on the hybridisation and stereochemistry covered in the nomenclature notes. The stereochemical outcomes of SN2, SN1, syn addition, and anti addition only make sense if you can assign R/S configurations and visualise three-dimensional molecular geometry. Spectroscopy (covered in the next set of study notes) is often used to confirm reaction products: you may need to interpret IR or NMR data to verify that a reaction produced the expected compound.
SN1, SN2, E1, E2, nucleophilic substitution, elimination reaction, electrophilic addition, Markovnikov, anti-Markovnikov, Zaitsev rule, Hofmann product, hydroboration, oxymercuration, mCPBA, epoxidation, Diels-Alder, cycloaddition, radical addition, NBS, allylic bromination, benzylic bromination, tosylate, TsCl, HBr ROOR, Lindlar catalyst, dissolving metal reduction, carbocation rearrangement, arrow-pushing mechanism, reagent matching, predict the product, CHEM 2301, organic chemistry I, UMN, Salmon