Difficulty: Intermediate to Advanced | Prerequisites: Alkene and alkyne reactions (Chapters 6–8), stereochemistry
Big Picture: Haloalkanes (alkyl halides) are the central hub of the reaction roadmap. They connect to almost every other functional group: alcohols, ethers, thiols, thioethers, nitriles, amines, alkyl azides, and back to alkenes and alkynes. The key challenge is predicting whether a haloalkane undergoes substitution (SN1 or SN2) or elimination (E1 or E2), and that decision depends on the substrate, the nucleophile/base, the solvent, and the temperature.
Haloalkanes react with nucleophiles (substitution) or bases (elimination) to form a wide range of products. Whether you get SN1, SN2, E1, or E2 depends on four variables: substrate structure (methyl/1°/2°/3°), nucleophile strength, solvent polarity, and temperature. This decision framework is the single most tested concept in Chapters 8-9.
Nucleophile
A species that donates an electron pair to an electrophilic carbon. Think of it as an electron-rich attacker. Common nucleophiles from the roadmap: NaCN, NaSH, NaSR, NaNR2, NaN3, NaOR, ROH, H2O, NaOH.
Leaving group
The group that departs with the bonding electrons during substitution or elimination. Good leaving groups are weak bases: halides (I- > Br- > Cl- >> F-), tosylate (OTs), water (after protonation of OH).
SN2 (bimolecular nucleophilic substitution)
A one-step mechanism: the nucleophile attacks the electrophilic carbon from the back side while the leaving group departs simultaneously. Rate = k[substrate][nucleophile]. In simple terms, one bond forms as the other breaks, in a single concerted step.
SN1 (unimolecular nucleophilic substitution)
A two-step mechanism: the leaving group departs first to form a carbocation, then the nucleophile attacks. Rate = k[substrate]. The carbocation intermediate means racemisation occurs (attack from both faces).
E2 (bimolecular elimination)
A one-step mechanism: a strong base removes a beta-hydrogen while the leaving group departs, forming a double bond. Requires anti-periplanar geometry (the H and the leaving group must be on opposite sides). Rate = k[substrate][base].
E1 (unimolecular elimination)
A two-step mechanism: the leaving group departs first (forming a carbocation), then a base removes a beta-hydrogen to form the double bond. Rate = k[substrate]. Often competes with SN1.
Zaitsev's rule
In elimination reactions, the more substituted alkene is the major product (the thermodynamically more stable one). This is the default for E1 and most E2 reactions.
Williamson ether synthesis
Formation of an ether by reacting an alkoxide (NaOR) with a primary haloalkane via SN2. The alkoxide is the nucleophile; the haloalkane provides the carbon electrophile.
Inversion of configuration
In SN2, the nucleophile attacks from the back side of the leaving group, flipping the stereochemistry at the carbon. Like an umbrella inverting in the wind.
This is the most important conceptual tool in Chapters 8-9. Work through the variables in this order:
Step 1: Look at the substrate
Methyl or primary: favours SN2 (or E2 with a strong, bulky base)
Secondary: borderline; depends on the nucleophile/base and solvent
Tertiary: SN2 is impossible (too sterically hindered); favours E2 (strong base) or SN1/E1 (weak nucleophile, polar protic solvent)
Step 2: Look at the nucleophile/base
Strong nucleophile (e.g. NaCN, NaSH, NaOR, NaN3): favours SN2
Strong, bulky base (e.g. tert-butoxide): favours E2
Weak nucleophile/base (e.g. H2O, ROH): favours SN1/E1
Step 3: Look at the solvent
Polar aprotic (DMSO, DMF, acetone): favours SN2 (nucleophile is "naked," not solvated)
Polar protic (water, alcohols): favours SN1/E1 (stabilises carbocation and leaving group)
Step 4: Temperature
Higher temperature favours elimination over substitution (entropy factor)
NaOH or H2O (E or J)
NaOH: strong nucleophile/base; with primary substrates gives SN2 (alcohol); with tertiary, E2 dominates
H2O: weak nucleophile; with tertiary substrates gives SN1 (alcohol) alongside E1 (alkene)
NaOR (E or J)
Alkoxide ion attacks a primary haloalkane via SN2
The alkoxide provides the oxygen; the haloalkane provides the carbon
Always use the less hindered haloalkane as the electrophile
ROH (an alcohol) as nucleophile gives ethers via SN1 with tertiary substrates
NaSH (I)
SN2 reaction, works best with primary and methyl substrates
Produces a thiol (R-SH), the sulphur analogue of an alcohol
NaSR (I)
SN2 reaction; sulphur nucleophiles are excellent because S is large and polarisable
Produces a thioether (R-S-R')
NaCN (I)
SN2 reaction; cyanide is a good nucleophile
Forms a new C-C bond (the carbon chain grows by one carbon)
Product is a nitrile (R-CN), which can be further converted to carboxylic acids or amines
NaNR2 or excess NH3 (I)
Nitrogen nucleophiles attack via SN2
Caution: over-alkylation is a problem (the product amine is also a nucleophile)
Gabriel synthesis or azide reduction are better routes for making primary amines cleanly
NaN3 (I)
SN2 reaction; azide is an excellent nucleophile
Produces an alkyl azide (R-N3)
Azides can be reduced to primary amines (a cleaner route than direct alkylation)
NaOR (strong base) or heat (K)
E2 with strong base: concerted, anti-periplanar geometry required
E1 with weak base/high temperature: goes through carbocation
Zaitsev's rule: more substituted alkene is the major product (usually)
Two successive eliminations from a vicinal or geminal dihalide
First elimination gives a vinyl halide; second elimination (with excess NaNH2) gives the alkyne
Requires a strong base like NaNH2
Students often think SN1 and SN2 are just "fast" and "slow" versions of the same reaction. They are fundamentally different mechanisms: SN2 is concerted (one step, backside attack, inversion); SN1 is stepwise (carbocation intermediate, racemisation).
A common mistake is trying to run SN2 on a tertiary substrate. This never works. The three bulky groups around the carbon block the nucleophile's approach entirely.
Students confuse nucleophilicity with basicity. A good nucleophile is not always a strong base. For example, I- is an excellent nucleophile but a weak base. tert-Butoxide is a strong base but a poor nucleophile (too bulky).
Many students forget that E2 requires anti-periplanar geometry. If the H and the leaving group cannot achieve a 180° dihedral angle, E2 cannot proceed from that conformation. This is especially relevant in cyclohexane systems where the H and X must both be axial.
⚠️ The SN1/SN2/E1/E2 decision framework is the most heavily tested topic in these chapters. Every exam will include at least one problem where you must predict the mechanism and products from a haloalkane + nucleophile/base combination.
⚠️ Stereochemistry of SN2: expect questions asking you to draw the product with correct stereochemistry (inversion at the carbon). Newman projections or wedge-dash drawings may be required.
⚠️ Williamson ether synthesis is a synthesis favourite. Know which component should be the alkoxide and which should be the haloalkane (the haloalkane must be primary or methyl for SN2).
⚠️ NaCN reactions form C-C bonds, making them valuable in synthesis problems where the product has more carbons than the starting material.
⚠️ Competing substitution and elimination: secondary substrates are the classic exam trap. The answer depends on the specific nucleophile/base and solvent.
True or False: SN2 reactions proceed with retention of configuration.
Fill in the blank: A tertiary haloalkane treated with a strong base will primarily undergo ______ (SN1/SN2/E1/E2).
True or False: NaN3 reacting with a primary haloalkane is an SN2 reaction.
Fill in the blank: In Williamson ether synthesis, the ______ should be primary or methyl to avoid elimination.
True or False: SN1 and E1 reactions both proceed through a carbocation intermediate.
Answers: 1. False (inversion of configuration). 2. E2. 3. True. 4. Haloalkane (the electrophile). 5. True.
Q: Predict the major product and mechanism when (R)-2-bromobutane is treated with NaCN in DMSO.
A: The product is (S)-2-methylbutanenitrile via SN2. NaCN is a strong nucleophile, DMSO is a polar aprotic solvent (favours SN2), and the substrate is secondary but not too hindered for cyanide. Inversion of configuration gives the S enantiomer.
Q: What happens when 2-bromo-2-methylpropane (tert-butyl bromide) is treated with NaOCH3 in ethanol?
A: E2 elimination to give 2-methylpropene (isobutylene). The substrate is tertiary (SN2 is impossible), and NaOCH3 is a strong base, so E2 dominates over SN1/E1.
Q: Show how to synthesise ethyl propyl ether using Williamson ether synthesis.
A: React sodium ethoxide (NaOCH2CH3) with 1-bromopropane. The ethoxide is the nucleophile; the primary haloalkane is the electrophile. Do not reverse these roles, because sodium propoxide + bromoethane also works, but if either component were secondary or tertiary, elimination would dominate.
Q: Predict the products when 1-bromobutane is treated with NaN3.
A: 1-azidobutane via SN2. Azide is an excellent nucleophile, and the primary substrate is ideal for SN2.
Q: Why does treating (R)-2-bromobutane with water in a polar protic solvent give a racemic mixture of 2-butanol?
A: Water is a weak nucleophile, and the secondary substrate can form a carbocation (SN1 pathway). The planar carbocation is attacked from both faces equally, giving a 50:50 mixture of R and S alcohols.
Haloalkanes sit at the centre of the reaction roadmap. Every arrow leaving the haloalkane box connects to a different functional group, and every arrow arriving at it comes from an alkene or alkane halogenation. If you can master haloalkane reactivity, you can navigate most of the synthesis problems in the first-year course.
The SN2 mechanism reappears in acetylide alkylation (Chapter 7-8) and later in enolate chemistry (Chapters 21-22). The E2 mechanism connects directly to alkene formation, tying back to alkene reactions in Chapters 6-7.
Alcohol chemistry (Chapter 10-11) extends these ideas: converting alcohols to haloalkanes reverses the direction, and many of the same nucleophiles and mechanisms apply.
Haloalkane reactions, alkyl halide, nucleophilic substitution, SN1, SN2, elimination, E1, E2, Williamson ether synthesis, leaving group, nucleophile, carbocation, inversion of configuration, racemisation, Zaitsev rule, anti-periplanar, NaCN nitrile synthesis, NaN3 azide synthesis, NaSH thiol synthesis, polar aprotic solvent, polar protic solvent, organic chemistry chapter 8 9, Purdue organic chemistry, reaction roadmap