Alkyl Halides

Theory — Alkyl Halides: Structure, Stereochemistry, Reactivity, and Synthesis

Alkyl halides (R–X, where X = F, Cl, Br, or I) are among the most versatile substrates in organic chemistry. The polarised C–X bond makes the carbon electrophilic and the halide an excellent leaving group, opening pathways to substitution and elimination products. This lab integrates everything you need to know about alkyl halides: how to draw and name them, how to assign their stereochemistry, how to predict their reactions, how to use them in synthesis, and how to handle them safely in a microscale laboratory.

1. Structure and IUPAC nomenclature (CLO 1)

Alkyl halides are named as substituted alkanes: the halogen is treated as a substituent (fluoro, chloro, bromo, iodo) on the longest carbon chain that contains it. Number the chain so the halogen receives the lowest possible locant. List substituents alphabetically. Common-name versus IUPAC-name conventions:

Structure	Common name	IUPAC name	Class
CH₃CH₂Br	ethyl bromide	bromoethane	1° (primary)
(CH₃)₂CHCl	isopropyl chloride	2-chloropropane	2° (secondary)
(CH₃)₃CBr	tert-butyl bromide	2-bromo-2-methylpropane	3° (tertiary)
CH₂=CH-CH₂Cl	allyl chloride	3-chloro-1-propene	allylic 1°
C₆H₅-CH₂Br	benzyl bromide	(bromomethyl)benzene	benzylic 1°

Hybridisation and geometry: the carbon bearing the halogen is sp³, with tetrahedral geometry (109.5° bond angles). The C–X bond is polar (δ⁻ on X, δ⁺ on C); the C–F bond is the strongest of the C–X bonds but the most reluctant leaving group, while C–I is the weakest bond and the best leaving group. This trend is critical for predicting reactivity in SN/E reactions.

2. Stereochemistry of alkyl halides (CLO 2)

An alkyl halide carbon is a stereocentre when it bears four different groups. Common stereogenic alkyl halides include 2-bromobutane, 2-chloropentane, and 1-bromo-1-phenylethane. The two non-superimposable mirror images of such a halide are enantiomers. The configuration at the stereocentre is assigned R or S using the Cahn-Ingold-Prelog (CIP) priority rules:

Rank the four groups bonded to the stereocentre by atomic number (highest priority = highest atomic number). For halides: I > Br > Cl > F.
If two groups have the same first atom, look at the next atoms outwards until a difference is found.
Orient the molecule so the lowest-priority group points away from you.
Trace the remaining three groups from highest to lowest priority. Clockwise = R; counterclockwise = S.

Worked example: (S)-2-bromobutane Stereocentre = C2 bearing Br, CH₃, CH₂CH₃, H
Priorities: Br (35) > CH₂CH₃ (next-sphere C,H,H) > CH₃ (H,H,H) > H
Wait — re-evaluate: CH₂CH₃ has substituents (C,H,H); CH₃ has (H,H,H). So CH₂CH₃ outranks CH₃.
Order: Br > CH₂CH₃ > CH₃ > H
If H points away and the rotation Br → CH₂CH₃ → CH₃ is counterclockwise → (S). Clockwise → (R).

Diastereomers and meso compounds. When a molecule has two or more stereocentres, multiple diastereomers exist. For a compound with two stereocentres, four stereoisomers are possible (RR, SS, RS, SR), unless internal symmetry makes one pair (RS = SR) the same achiral molecule — a meso compound. Example: (2R,3S)-2,3-dibromobutane is meso because the molecule has an internal mirror plane.

3. SN1, SN2, E1, E2 reactions (CLO 5)

Alkyl halides participate in four key reaction types. Knowing which mechanism operates lets you predict product, regiochemistry, and stereochemistry:

SN2 — bimolecular substitution

One step, concerted. Nucleophile attacks the C-X carbon from the back; X leaves simultaneously. Stereochemistry: inversion at the carbon (Walden inversion). Kinetics: rate = k[R-X][Nu⁻]. Best for 1° halides; 3° halides do not undergo SN2 (too crowded).

SN1 — unimolecular substitution

Two steps: X leaves first, generating a carbocation; nucleophile then attacks the planar cation from either face → racemisation at the original stereocentre. Kinetics: rate = k[R-X]. Best for 3° halides; 1° halides do not undergo SN1 (1° cation too unstable).

E2 — bimolecular elimination

One step, concerted. Strong base removes a β-H while X leaves and the C=C π bond forms. Stereochemistry: anti-periplanar arrangement of H and X required. Regiochemistry: Zaitsev (more substituted alkene) is normally favoured; Hofmann (less substituted) is favoured with bulky bases.

E1 — unimolecular elimination

Two steps: X leaves first (cation forms), then β-H is lost to a weak base. Kinetics: rate = k[R-X]. Stereochemistry: Zaitsev favoured (thermodynamic control). Best for 3° halides under solvolysis conditions; competes with SN1.

Carbocation rearrangements. In SN1 and E1 reactions, the carbocation intermediate may rearrange via 1,2-hydride or 1,2-methyl shifts to a more stable cation. Always check whether a more stable cation is one shift away — the rearranged product is often the major product.

4. Substitution vs. elimination — predicting the outcome

Whether an alkyl halide gives SN, E, or a mixture depends on five factors. The most useful decision matrix:

Factor	Favours SN2	Favours SN1/E1	Favours E2
Substrate	1° > 2° >> 3° (none)	3° > 2° (no 1°)	3° > 2° > 1°
Nucleophile/base	Strong nucleophile, weak base (CN⁻, I⁻, RS⁻)	Weak nucleophile (H₂O, ROH)	Strong, hindered base (t-BuO⁻, LDA)
Solvent	Polar aprotic (DMSO, DMF, acetone)	Polar protic (H₂O, ROH)	Polar aprotic; or alcoholic KOH
Temperature	Lower (room temp OK)	Higher	Higher (heat drives elimination)
Leaving group	I⁻ > Br⁻ > Cl⁻ >> F⁻	Same trend	Same trend

Quick decision rules for a problem set:

1° halide + strong nucleophile (CN⁻, RS⁻, NaN₃) → SN2
1° halide + bulky strong base (t-BuO⁻) → E2 (Hofmann product)
3° halide + weak nucleophile in protic solvent (H₂O, ROH) → SN1/E1 mixture
3° halide + strong base (NaOH, NaOEt) → E2 (Zaitsev product)
2° halide — most ambiguous; examine all conditions carefully
Vinyl or aryl halide (X on sp² carbon) → unreactive in SN/E (no special activation)

5. Synthesis: making and using alkyl halides (CLO 7)

Alkyl halides are central to synthetic strategy because they can be made from many sources and they can be converted into many functional groups. The two most useful synthetic operations:

Making alkyl halides from alcohols:

R–OH + HX → R–X + H₂O (works best for 3° alcohols; 1°/2° alcohols may need PBr₃ or SOCl₂)
R–OH + PBr₃ → R–Br + HOPBr₂ (clean conversion of 1°/2° alcohols to bromides; SN2-like, with inversion)
R–OH + SOCl₂ → R–Cl + SO₂ + HCl (clean conversion; with pyridine, retention of configuration via SNi)

Making alkyl halides from alkenes:

Alkene + HX → alkyl halide (Markovnikov; via carbocation)
Alkene + HBr/peroxides → 1° alkyl bromide (anti-Markovnikov; radical chain)
Alkene + Br₂ → vicinal dibromide (anti addition)

Converting alkyl halides into other functional groups:

R–X + NaCN → R–CN (nitrile; useful precursor to carboxylic acids and amines)
R–X + NaSR' → R–S–R' (thioether)
R–X + NaOR' → R–O–R' (ether — Williamson synthesis; needs 1° halide for SN2)
R–X + NaN₃ → R–N₃ → R–NH₂ (after reduction)
R–X + Mg → R–MgX (Grignard reagent — converts halide into a nucleophilic carbon for C–C bond formation)
R–X + strong base → alkene (E2)

A multi-step synthesis often uses an alkyl halide as a connector — convert an alcohol or alkene to a halide, then SN2 or Grignard to install a new group.

6. Microscale operations and SDS for halide reagents (CLO 8)

Working with alkyl halides safely requires understanding the hazards of both the halides themselves and the reagents used to convert them. Most alkyl halides are volatile, lipophilic, and have varying degrees of toxicity — many are suspected carcinogens. The following microscale techniques are essential:

Boiling point determination

Most alkyl halides are liquids at room temperature with characteristic boiling points (e.g. 2-bromobutane: 91 °C; 1-chlorobutane: 78 °C). Microscale b.p. on a Thiele tube confirms identity. Always work in a fume hood — alkyl halide vapours are toxic.

Refractive index n_D²⁰

Highly characteristic for halides because the heavy halogen substantially raises n_D (e.g. 1-bromobutane: n_D²⁰ = 1.4400; 1-iodobutane: 1.5001). Measured on Abbé refractometer.

Density and partition

Most alkyl halides (Br, I) are denser than water — they sink in extraction. This influences the position of the organic layer in a separatory funnel (water layer on top for Br/I halides; on bottom for Cl halides typically).

SDS hazards

Common hazards: highly flammable (most alkyl halides except CCl₄); toxic by inhalation; suspected carcinogen (CCl₄, CHCl₃, CH₂Cl₂); skin/eye irritant. PPE: nitrile gloves, goggles, fume hood mandatory.

Disposal: alkyl halides go into the halogenated organic waste container, never down the drain. Keep separate from non-halogenated solvents.

Instructions

This lab's Simulation section has four parts. Complete them in order.

Section I — Structure & Naming (CLO 1, 2). Eight alkyl halide structures are presented. For each, identify the IUPAC name, the substrate class (1°/2°/3°), and (where applicable) the R/S configuration of the stereocentre.

Section II — Reaction Predictor (CLO 5). Twelve reactions are presented, each combining an alkyl halide with a nucleophile/base and conditions. Predict the operative mechanism (SN1/SN2/E1/E2) and the major product. Track score live.

Section III — Synthesis Design (CLO 7). Six retrosynthesis problems: starting from a defined precursor (alkene, alcohol, or simple alkyl halide), design a multi-step route to a target compound. Choose reagent sequences that achieve the required regiochemistry and stereochemistry.

Section IV — SDS & Microscale Workbench (CLO 8). SDS interpretation for four halide reagents (HBr, PBr₃, SOCl₂, CH₂Cl₂); microscale data matching for five alkyl halide compounds; theoretical and percent yield calculations for two complete experiments.

Prepare your lab report. Use the Example Report as your template. Your report must include a reagent table with hazard data, all stereochemical assignments, mechanistic justifications for each predicted product, and at least one yield calculation.

Safety note: Many alkyl halides and the reagents used to make them are toxic and/or suspected carcinogens. CCl₄, CHCl₃, CH₂Cl₂, and 1,2-dichloroethane are particularly hazardous. PBr₃ and SOCl₂ react violently with water. In a real lab, work in the fume hood with gloves, goggles, and lab coat. In this virtual lab you're safe — but the goal is to learn to recognise and respect these hazards.

Simulation

Four interactive parts — work through them in order.

For each structure, answer three questions: (a) IUPAC name, (b) substrate class (1°/2°/3°/methyl), and (c) R/S configuration if a stereocentre is present. Click each answer; live feedback explains the reasoning.

Score: 0 / 24 (3 questions × 8 compounds)

For each reaction, predict (a) the operative mechanism and (b) the major product. Match reaction conditions to the SN1/SN2/E1/E2 decision matrix in the Theory section.

Score: 0 / 24 (2 questions × 12 reactions)

Six retrosynthesis problems. For each, choose the correct reagent or reagent sequence.

Score: 0 / 6

Round 1 — SDS interpretation

Each card shows an SDS extract for a reagent commonly used in alkyl halide synthesis. Answer the four questions about hazards, PPE, disposal, and first aid.

SDS score: 0 / 16 (4 questions × 4 reagents)

Round 2 — Microscale data matching

Five microscale measurement records — match each to the correct alkyl halide based on b.p., n_D²⁰, and density.

Candidate compounds (each used exactly once):

1-Chlorobutane — colourless liquid, b.p. 78 °C, n_D²⁰ = 1.4021, density 0.886 g/mL
1-Bromobutane — colourless liquid, b.p. 102 °C, n_D²⁰ = 1.4400, density 1.276 g/mL
2-Bromobutane — colourless liquid, b.p. 91 °C, n_D²⁰ = 1.4358, density 1.258 g/mL
1-Iodobutane — colourless liquid (yellows on standing), b.p. 130 °C, n_D²⁰ = 1.5001, density 1.617 g/mL
tert-Butyl chloride — colourless liquid, b.p. 51 °C, n_D²⁰ = 1.3857, density 0.842 g/mL

Microscale score: 0 / 5

Round 3 — Theoretical and percent yield

Calculate yields for two alkyl halide syntheses. ±5% tolerance.

Yield score: 0 / 3

Team Questions

Discuss with your team. Each question targets one of the CLOs covered in this lab.

Question 1 — CLO 1 (structure & naming). Draw the bond-line structure of (R)-2-bromo-3-methylpentane and assign the IUPAC name to the structure CH₃CH(Br)CH(CH₃)CH₂CH₃ — verify they match. What is the hybridisation and geometry of the carbon bearing the bromide?

Question 2 — CLO 2 (stereochemistry). 2,3-Dibromobutane has three stereoisomers: (2R,3R), (2S,3S), and (2R,3S). The (2R,3S) form is achiral. Why? Use the term "meso" in your answer. Hint: look for an internal mirror plane.

Question 3 — CLO 5 (mechanism). 2-Bromo-2-methylbutane is heated in aqueous ethanol with no added base. Predict the major mechanism (SN1, SN2, E1, or E2) and the major product. Justify with one sentence about substrate, nucleophile, and solvent.

Question 4 — CLO 5 (stereochemistry of mechanism). (R)-2-bromobutane reacts with NaCN in DMSO. What stereochemistry does the product have, and what is the operative mechanism? Why?

Question 5 — CLO 7 (synthesis). Propose a two-step synthesis of pentanenitrile (CH₃CH₂CH₂CH₂CN) from 1-pentanol. Name each reagent and the operative mechanism in each step.

Question 6 — CLO 8 (lab skills). A student is converting 2.50 g of 2-methyl-2-propanol (M.W. 74.12) into 2-bromo-2-methylpropane (M.W. 137.02) using HBr. After workup, 3.20 g of product is isolated. Calculate the percent yield. (Hint: 1:1 stoichiometry.)

Example Lab Report

Sample report demonstrating the expected ACS-style format. Use as a template for your own submission.

Alkyl Halides: Structure, Stereochemistry, Mechanism, and Synthesis

Submitted by: [Student Name]

Course: Organic Chemistry · Section: 221-A · Date: April 24, 2026

Abstract

This comprehensive lab examined the structural, stereochemical, mechanistic, and synthetic aspects of alkyl halide chemistry. Eight alkyl halides were named using IUPAC conventions and classified by substrate type; six contained stereocentres assigned R or S using CIP priority rules. Twelve reaction conditions were analysed to predict the operative mechanism (SN1/SN2/E1/E2) and the major product. Six retrosynthesis problems were solved, requiring multi-step routes that combined alcohol-to-halide conversions with subsequent SN/E reactions. Safety data sheets for HBr, PBr₃, SOCl₂, and dichloromethane were interpreted to extract hazard, PPE, and disposal data. Microscale physical-property data for five common alkyl halides were matched to literature values to confirm identity. Theoretical and percent yields were calculated for the conversion of 1-butanol to 1-bromobutane (achieved 79% yield) and for the SN2 conversion of 2-bromobutane to 2-cyanobutane (88% yield).

Introduction

Alkyl halides occupy a central position in organic synthesis because the polarised C–X bond combines an electrophilic carbon with a competent leaving group. This dual nature enables alkyl halides to participate in two fundamentally different reaction families — nucleophilic substitution (SN) and elimination (E) — each with two limiting mechanisms (SN1/SN2 and E1/E2). Predicting which of these four pathways predominates requires reasoning about substrate class, nucleophile and base strength, leaving group, solvent, and temperature. The same alkyl halide may give entirely different products under different conditions, making mechanistic mastery essential for both forward prediction and retrosynthetic design. This lab tests these abilities through structural drawing, stereochemical assignment, mechanism prediction, multi-step synthesis design, and safe microscale handling.

Reagents and Hazards (drawn from SDS)

Before each experiment, the SDS for every reagent was consulted. Section 2 (Hazards), Section 8 (PPE), Section 9 (Properties), and Section 13 (Disposal) of each SDS provided the data summarised below.

Reagent	Major hazard	PPE	Key §9 data	Disposal
HBr (48% aq)	Corrosive (H314); evolves HBr vapour	Goggles, nitrile gloves, lab coat, fume hood	Pale yellow liquid; b.p. 124 °C; density 1.49 g/mL	Neutralise with NaHCO₃, aqueous waste
PBr₃	Reacts violently with water; corrosive (H314); H290	Goggles, nitrile gloves, lab coat, fume hood; dry conditions	Colourless fuming liquid; b.p. 173 °C; density 2.85 g/mL	Quench cautiously with cold water in fume hood, then aqueous waste
SOCl₂ (thionyl chloride)	Reacts violently with water; corrosive; toxic (H314, H331)	Goggles, nitrile gloves, lab coat, fume hood; dry conditions	Pale yellow fuming liquid; b.p. 76 °C; density 1.64 g/mL	Quench with ice in fume hood; collect as halogenated waste
NaCN	Acutely toxic (H300, H310, H330); evolves HCN if acidified	Goggles, nitrile gloves, lab coat, fume hood; never acidify	White hygroscopic solid; M.W. 49.01	Strict cyanide waste container; never mix with acid
CH₂Cl₂ (DCM)	Suspected carcinogen (H351); H315, H319, H336	Goggles, nitrile gloves, lab coat, fume hood	Colourless volatile liquid; b.p. 40 °C; density 1.33 g/mL	Halogenated organic waste
NaOEt / EtOH	Flammable (EtOH); strongly basic; corrosive	Goggles, gloves, lab coat; no flames nearby	Clear ethanolic solution	Neutralise then organic solvent waste

All reactions were run microscale: 0.5–1.0 mmol substrate in 1.0–3.0 mL solvent. PBr₃ and SOCl₂ reactions were strictly anhydrous (oven-dried glassware, dry solvents).

Results — Section I: Structure and Naming

Cmpd	IUPAC name	Class	Stereocentre	Configuration
A	1-bromobutane	1°	None	—
B	2-bromobutane	2°	C2	R or S (drawn as R)
C	2-bromo-2-methylpropane	3°	None (no 4 different groups)	—
D	(2R,3R)-2,3-dibromobutane	2°,2°	C2 and C3	R, R
E	(2R,3S)-2,3-dibromobutane (meso)	2°,2°	C2 and C3	R, S — meso
F	(R)-1-chloro-1-phenylethane	1° benzylic (or 2° depending on definition)	C1	R
G	3-chloro-1-propene (allyl chloride)	1° allylic	None	—
H	iodocyclohexane	2°	None (chiral centre present but mirror plane through ring)	—

Results — Section II: Reaction Mechanism Predictions

#	Substrate	Conditions	Mechanism	Major product
1	1-bromobutane	NaCN, DMSO	SN2	pentanenitrile
2	2-bromo-2-methylpropane	EtOH, heat	SN1/E1	tert-butyl ethyl ether + 2-methylpropene
3	(R)-2-bromobutane	NaI, acetone	SN2	(S)-2-iodobutane (Walden inversion)
4	2-bromo-2-methylbutane	NaOEt, EtOH, heat	E2	2-methyl-2-butene (Zaitsev)
5	2-bromo-2-methylbutane	KOtBu, t-BuOH, heat	E2 (Hofmann)	2-methyl-1-butene (Hofmann)
6	3-bromopentane	NaCN, DMF	SN2 (some E2 possible)	3-cyanopentane
7	2-chloro-2-methylpropane	H₂O	SN1/E1	2-methyl-2-propanol + 2-methylpropene
8	chloromethane	NaSR, DMSO	SN2	methyl thioether
9	1-chloropropane	NaOMe, MeOH	SN2 (mostly), some E2	1-methoxypropane
10	(R)-2-iodobutane	aq EtOH, no base, heat	SN1/E1	racemic 2-butanol + 2-butene
11	2-bromo-3-methylbutane	NaOEt, EtOH, heat	E2 (from anti-periplanar β-H)	2-methyl-2-butene (Zaitsev)
12	vinyl bromide	NaCN, DMSO	No reaction	vinyl halides do not undergo SN/E at sp² C

Results — Section III: Multi-step Syntheses

Six retrosynthesis problems were solved. Two representative cases:

Target: pentanenitrile from 1-pentanol. Step 1: 1-pentanol + PBr₃ → 1-bromopentane (SN2 at the carbon, with inversion at any stereocentre). Step 2: 1-bromopentane + NaCN in DMSO → pentanenitrile (SN2; cyanide is a strong nucleophile and a poor base).

Target: 2-methyl-2-butene from 2-methyl-2-butanol. Step 1: 2-methyl-2-butanol + HCl → 2-chloro-2-methylbutane (SN1; tertiary alcohol). Step 2: 2-chloro-2-methylbutane + NaOEt, EtOH, heat → 2-methyl-2-butene (E2, Zaitsev).

Alternative for the elimination: direct dehydration of the tertiary alcohol with conc. H₂SO₄/heat gives the same alkene by E1 in one step.

Results — Section IV: Microscale Verification

The product of the 1-butanol → 1-bromobutane synthesis (using HBr/H₂SO₄) was characterised by three independent microscale measurements and compared to literature values (SDS Section 9):

Measurement	Method	Observed	Literature	Conclusion
Boiling point	Microscale b.p. (Thiele tube)	101.5–102.5 °C	102 °C	Match within ±0.5 °C
Refractive index n_D²⁰	Abbé refractometer	1.4398	1.4400	Match within ±0.001
Density	Microscale pipette + balance	1.275 g/mL	1.276 g/mL	Match — pure

Theoretical and Percent Yield

Experiment 1 — 1-butanol → 1-bromobutane (HBr/H₂SO₄):

Quantity	Value
Starting material: 1-butanol (M.W. 74.12)	1.50 g (0.02024 mol)
Stoichiometry	1:1 (1 mol alcohol → 1 mol R–Br)
Theoretical mass: 1-bromobutane (M.W. 137.02)	0.02024 × 137.02 = 2.773 g
Mass isolated	2.20 g
Percent yield	2.20 / 2.773 × 100 = 79.3%

Experiment 2 — 2-bromobutane → 2-cyanobutane (NaCN/DMSO):

0.685 g of 2-bromobutane (M.W. 137.02) = 5.00 mmol. SN2 with NaCN gives 2-cyanobutane (M.W. 83.13) at 1:1 stoichiometry. Theoretical mass = 5.00 × 10⁻³ × 83.13 = 0.4157 g. Mass isolated = 0.366 g. Percent yield = 88.0%.

Discussion

Stereochemistry of mechanism. The (R)-2-bromobutane → (S)-2-iodobutane conversion (entry 3 of Section II) confirms the SN2 mechanism through Walden inversion. In contrast, when (R)-2-iodobutane is solvolysed in aqueous ethanol (entry 10), the product is racemic 2-butanol — consistent with the SN1 mechanism, where the planar carbocation is attacked from either face with equal probability.

Substrate effect on mechanism choice. Comparing entries 1 (1° + strong nucleophile → SN2) and 2 (3° + weak nucleophile → SN1/E1) illustrates how substrate class drives mechanism. The 1° carbocation that would form in SN1 is too unstable to be accessed, so 1° halides default to SN2 with strong nucleophiles. The 3° SN2 transition state is too sterically crowded, so 3° halides default to SN1 (when nucleophile is weak) or E2 (when base is strong).

Hofmann versus Zaitsev. Entries 4 and 5 use the same substrate (2-bromo-2-methylbutane) but different bases. NaOEt (small) gives the Zaitsev product (2-methyl-2-butene, more substituted alkene, thermodynamically favoured). KOtBu (bulky) cannot easily reach the more-hindered β-H and instead removes the less-hindered β-H, giving the Hofmann product (2-methyl-1-butene). This is a clean illustration of base size controlling regiochemistry in E2.

Microscale data confirm identity. The product of the 1-butanol → 1-bromobutane synthesis matched all three literature values within ±0.5 °C (b.p.), ±0.001 (n_D), and ±0.001 g/mL (density). This combination of three independent measurements is more diagnostic than any single one: a sample that matches all three is essentially certain to be the proposed compound.

Yield analysis. The 79.3% yield from 1-butanol → 1-bromobutane is consistent with literature values for HBr/H₂SO₄ on a 1° alcohol. The 88.0% yield for the SN2 with cyanide is excellent and reflects the favourable substrate (1° → 2° SN2 with a strong nucleophile in DMSO). Losses in both cases were primarily mechanical (transfers, evaporation of volatile bromide) plus some unreacted starting material recovered after workup.

Conclusions

All four CLOs targeted in this lab were addressed. CLO 1 (structure and naming) was demonstrated through correct IUPAC names and class assignments for all eight compounds. CLO 2 (stereochemistry) was demonstrated through R/S assignments and the recognition of the meso compound. CLO 5 (mechanism) was demonstrated through correct mechanism prediction for all twelve reactions. CLO 7 (synthesis) was demonstrated through six successful retrosynthesis solutions. CLO 8 (lab skills) was demonstrated through correct interpretation of four SDSs, accurate matching of microscale data to literature values, and successful yield calculations for two complete experiments.

References

1. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed., Oxford University Press, 2012, Ch. 17, 19, 22.
2. Smith, M. B. March's Advanced Organic Chemistry, 8th ed., Wiley, 2020, Ch. 10, 17.
3. Sigma-Aldrich Safety Data Sheets, accessed via online catalogue, March 2026.
4. Pavia, D. L.; Lampman, G. M.; Kriz, G. S.; Engel, R. G. A Microscale Approach to Organic Laboratory Techniques, 6th ed., Cengage, 2018.

Practice Questions

Test your understanding. Try each one before peeking at the hint.

Practice 1 — CLO 1

Give the IUPAC name and the class (1°/2°/3°) of (CH₃)₂CHCH(Cl)CH₂CH₃. Identify the hybridisation and approximate bond angle at the carbon bearing chlorine.

Hint: 3-chloro-2-methylpentane; 2° (the Cl-bearing C has two carbon neighbours plus an H and a Cl); sp³, ~109.5°.

Practice 2 — CLO 1 + 2

For (R)-2-bromobutane and (S)-2-bromobutane: are these constitutional isomers, geometric isomers, enantiomers, or diastereomers? Are their physical properties (m.p., b.p., density) identical or different? What about their interaction with plane-polarised light?

Hint: enantiomers; identical b.p./m.p./density and most other physical properties; opposite specific rotations (one rotates light clockwise, the other counterclockwise by the same magnitude).

Practice 3 — CLO 2

2,3-dichloropentane has how many possible stereoisomers? List them by configuration (e.g. (2R,3R), etc.) and identify any that are achiral (meso).

Hint: Four stereoisomers: (2R,3R), (2S,3S), (2R,3S), (2S,3R). The (2R,3S) and (2S,3R) are NOT meso here because the two ends are different (CH₃ vs CH₂CH₃). All four are chiral; (R,R)/(S,S) are one pair of enantiomers; (R,S)/(S,R) are the other pair (diastereomeric to the first pair). Compare to 2,3-dichlorobutane, where the (R,S) form IS meso.

Practice 4 — CLO 5

Predict the major product and the mechanism for: (a) (R)-2-bromopentane + NaSCH₃ in DMSO; (b) 2-bromo-2-methylpentane + KOtBu in t-BuOH, heat; (c) 1-bromohexane + NaOH in 50% aqueous ethanol, heat.

Hint: (a) (S)-2-(methylthio)pentane via SN2 with inversion (1° class is wrong — this is 2° with a strong soft nucleophile + polar aprotic solvent → SN2). (b) 4-methylpent-1-ene (Hofmann product) via E2 with bulky base. (c) 1-hexanol via SN2 (some E2 possible at high T) — primary halide with strong nucleophile in protic solvent.

Practice 5 — CLO 5 (rearrangement)

3-Bromo-2,2-dimethylbutane is heated in aqueous ethanol. Two products are possible: 2,2-dimethyl-3-butanol (no rearrangement) and 2,3-dimethyl-2-butanol (rearranged). Which is the major product, and why?

Hint: 2,3-dimethyl-2-butanol is the major product. The initial 2° carbocation rearranges by a 1,2-methyl shift (from the adjacent quaternary carbon) to a much more stable 3° carbocation. Water then attacks the 3° cation. Always check whether a 1,2-shift gives a more-stable cation — if yes, the rearranged product dominates.

Practice 6 — CLO 7 (synthesis)

Design a synthesis of 1-butanethiol (CH₃CH₂CH₂CH₂SH) from 1-butanol. State each reagent and the operative mechanism. (Hint: use thiourea / NaOH as one route, or NaSH directly via the bromide.)

Hint: Two-step route: Step 1: 1-butanol + PBr₃ → 1-bromobutane (clean SN2 at the alcohol C). Step 2: 1-bromobutane + NaSH (or thiourea then NaOH) in DMF or DMSO → 1-butanethiol via SN2. Alternative: 1-bromobutane + thiourea → S-alkylisothiouronium salt; then NaOH hydrolysis releases the thiol. Avoid direct R-OH → R-SH attempts; thiols are not usually made directly from alcohols.

Practice 7 — CLO 7 (multi-step)

Propose a synthesis of 2-methylbutan-2-ol from 2-bromo-2-methylbutane that uses an SN1 mechanism and a synthesis of (S)-2-pentanol from (R)-2-bromopentane that goes through SN2.

Hint: SN1 on 2-bromo-2-methylbutane: just heat in water (3° halide, weak nucleophile, polar protic solvent → SN1 → 2-methyl-2-butanol). For the SN2: (R)-2-bromopentane + NaOH in DMSO (2° halide, strong nucleophile, polar aprotic solvent → SN2 with Walden inversion → (S)-2-pentanol).

Practice 8 — CLO 8 (SDS)

A student needs to use phosphorus tribromide (PBr₃). Before opening the bottle, the student reads the SDS. State (a) why the reagent must NOT contact water, (b) the required PPE, (c) the disposal route, (d) the first-aid response if PBr₃ contacts skin.

Hint: (a) PBr₃ + 3 H₂O → H₃PO₃ + 3 HBr — violent exotherm with HBr fume evolution. (b) goggles, gloves, lab coat, fume hood mandatory; dry glassware. (c) Quench cautiously with cold water in fume hood, neutralise the resulting acidic solution with NaHCO₃, then dispose as aqueous waste. (d) Brush off solid first if any, then rinse 15 min with water; remove contaminated clothing; medical attention.

Practice 9 — CLO 8 (microscale)

A student isolates a colourless liquid and measures b.p. = 91 °C, n_D²⁰ = 1.4358, density = 1.258 g/mL. Two candidates were proposed from the synthesis: 2-bromobutane (b.p. 91 °C, n_D²⁰ = 1.4358, density 1.258) and 1-chloropentane (b.p. 108 °C, n_D²⁰ = 1.4127, density 0.882). Which is the product? How precise are the measurements?

Hint: 2-bromobutane — every observed value matches the literature within microscale precision (±0.5 °C for b.p., ±0.001 for n_D, ±0.001 g/mL for density). 1-chloropentane is excluded by all three measurements (b.p. off by 17 °C, n_D off by 0.023, density off by 0.376 g/mL).

Practice 10 — CLO 8 (yield)

Synthesis of 1-iodobutane from 1-butanol via two steps: (1) 1-butanol + PBr₃ → 1-bromobutane (yield in this step: 75%); (2) 1-bromobutane + NaI in acetone → 1-iodobutane (Finkelstein; yield 90%). Starting from 5.00 g of 1-butanol (M.W. 74.12), calculate the expected mass of 1-iodobutane (M.W. 184.02) at the end of the two-step sequence.

Hint: moles 1-butanol = 5.00 / 74.12 = 0.06746 mol. Theoretical 1-bromobutane (1:1) = 0.06746 mol; actual after step 1 = 0.06746 × 0.75 = 0.05060 mol. Theoretical 1-iodobutane (1:1) = 0.05060 mol; actual after step 2 = 0.05060 × 0.90 = 0.04554 mol. Expected mass = 0.04554 × 184.02 = 8.38 g. Overall yield = 0.75 × 0.90 = 67.5%.