Alcohols

Theory — Alcohols: Structure, Stereochemistry, Reactivity, and Synthesis

Alcohols (R–OH) are organic compounds with a hydroxyl group bonded to an sp³ carbon. The polarised C–O bond combined with the polar O–H bond gives alcohols a unique reactivity profile: the oxygen is nucleophilic, the proton is mildly acidic (pK_a ≈ 16–18), and the C–OH bond can be activated for substitution and elimination reactions. This lab integrates everything you need to know about alcohols: 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)

Alcohols are named with the suffix -ol. Find the longest carbon chain that includes the OH-bearing carbon, number the chain so OH gets the lowest possible locant, and add substituents as prefixes. Older common names use the alkyl group + "alcohol" (e.g., ethyl alcohol).

Structure	Common name	IUPAC name	Class
CH₃OH	methyl alcohol (methanol)	methanol	special (no carbons attached to C-OH)
CH₃CH₂OH	ethyl alcohol	ethanol	1° (primary)
(CH₃)₂CHOH	isopropyl alcohol	propan-2-ol (or 2-propanol)	2° (secondary)
(CH₃)₃COH	tert-butyl alcohol	2-methylpropan-2-ol	3° (tertiary)
HOCH₂CH₂OH	ethylene glycol	ethane-1,2-diol	1°,1° (diol)
C₆H₅OH	phenol	phenol (acceptable as IUPAC base name)	aromatic (NOT a typical alcohol)
CH₂=CHCH₂OH	allyl alcohol	prop-2-en-1-ol	1° allylic
C₆H₅CH₂OH	benzyl alcohol	phenylmethanol	1° benzylic

Hybridisation and geometry: the carbon bearing OH is sp³ (tetrahedral, 109.5°). The oxygen is also sp³ — the C-O-H angle is about 104.5° (slightly compressed by the two lone pairs on O). The C-O bond is polar (δ⁻ on O, δ⁺ on C), and the O-H bond is highly polar (δ⁻ on O, δ⁺ on H), giving alcohols significant intermolecular hydrogen bonding. This is why alcohols have much higher boiling points than alkanes of similar molecular weight (e.g., ethanol b.p. 78 °C vs propane b.p. –42 °C).

2. Stereochemistry of alcohols (CLO 2)

An alcohol carbon is a stereocentre when it bears four different groups. Common stereogenic alcohols include 2-butanol, 2-pentanol, 1-phenylethanol. The configuration at the stereocentre is assigned R or S using the Cahn-Ingold-Prelog (CIP) priority rules:

Rank the four groups by atomic number (highest priority first). Note: OH outranks any carbon group.
If two groups have the same first atom, look outwards.
Orient the molecule so the lowest-priority group (usually H) points away.
Trace the remaining three from highest to lowest. Clockwise = R; counterclockwise = S.

Worked example: (S)-2-butanol Stereocentre = C2 bearing OH, CH₃, CH₂CH₃, H
Priorities: OH (O = 8) > CH₂CH₃ (next-sphere C,H,H) > CH₃ (H,H,H) > H
Order: OH > CH₂CH₃ > CH₃ > H
If H points away and the rotation OH → CH₂CH₃ → CH₃ is counterclockwise → (S). Clockwise → (R).

Diols and meso compounds. Compounds with two OH groups (diols) can have multiple stereocentres. Tartaric acid (2,3-dihydroxysuccinic acid) is the classic example: (2R,3R) and (2S,3S) are enantiomers; (2R,3S) is a meso compound (achiral due to internal mirror plane). The same applies to 2,3-butanediol: (2R,3R)/(2S,3S) are enantiomers, (2R,3S) is meso.

Stereochemistry of alcohol reactions. Reactions at the C–OH carbon retain or invert configuration depending on mechanism: SN2-like processes (PBr₃ acting on alcohol, SOCl₂ + amine base) give inversion; SN1-like processes (3° alcohols + HX, or solvolysis after tosylation) give racemisation; SOCl₂ alone (no base) goes through an SNi mechanism and gives retention.

3. Reactions of alcohols (CLO 5)

Alcohols undergo five major classes of reaction. Knowing which mechanism operates determines the product, regiochemistry, and stereochemistry:

Acid-catalysed dehydration

R-OH → alkene + H₂O with conc. H₂SO₄ or H₃PO₄, heat. Mechanism: E1 (3°/2° alcohols) or E2 (1° alcohols at very high T). Regiochemistry: Zaitsev (more substituted alkene). Reactivity: 3° > 2° >> 1°. Carbocation rearrangement is common in 3°/2° pathways.

Conversion to alkyl halide

R-OH → R-X. Multiple reagents: HX (best for 3°), PBr₃ (best for 1°/2° → R-Br, with inversion), SOCl₂ (best for 1°/2° → R-Cl, with retention if pyridine added — SNi). Direct OH → leaving group replacement enables subsequent SN/E chemistry.

Oxidation

1° R-CH₂OH → R-CHO (aldehyde) → R-COOH (carboxylic acid). PCC or Swern stops at the aldehyde; Jones (CrO₃/H₂SO₄) or KMnO₄ goes all the way to the acid. 2° R₂CH-OH → R₂C=O (ketone) with any oxidant. 3° alcohols are inert to oxidation (no α-H on the OH carbon).

Williamson ether synthesis

R-OH + NaH → R-O⁻ Na⁺; then R'-X → R-O-R'. The alkoxide is a strong nucleophile that performs SN2 on a primary alkyl halide. The R' group MUST be 1° (or methyl) — 3° R'-X gives elimination instead. Hence "(more substituted) alkoxide + (less substituted) R-X" is the strategic rule.

Tosylation and mesylation. The OH group can be activated by converting it to a tosylate (R-O-Ts, from TsCl + pyridine) or mesylate (R-O-Ms, from MsCl + Et₃N). The tosylate/mesylate is an excellent leaving group, making the carbon highly susceptible to SN2 by any good nucleophile. This is the cleanest way to convert R-OH to R-Nu while preserving stereochemistry (one inversion in the SN2 step).

4. Synthesis: making alcohols (CLO 7)

Alcohols can be made by multiple routes. The most useful for synthesis design:

From alkenes:

Alkene + H₂O/H₂SO₄ → Markovnikov alcohol (acid-catalysed hydration; through carbocation, may rearrange)
Alkene + Hg(OAc)₂/H₂O; then NaBH₄ → Markovnikov alcohol without rearrangement (oxymercuration-demercuration)
Alkene + BH₃/THF; then H₂O₂/NaOH → anti-Markovnikov alcohol (hydroboration-oxidation)

From carbonyl compounds (preview for upcoming reactions):

Aldehyde + NaBH₄ → 1° alcohol; ketone + NaBH₄ → 2° alcohol
Aldehyde + R'MgX → 2° alcohol (after H₃O⁺); ketone + R'MgX → 3° alcohol
Ester + 2 R'MgX → 3° alcohol (with two identical R' groups added)

From alkyl halides:

R-X + NaOH (1° X, polar protic) → R-OH via SN2 (or SN1 for 3° X)
R-X + AgNO₃/H₂O (drives off X⁻ as AgX) → R-OH

Multi-step strategy. A common synthesis pattern: start with an alcohol, convert to halide or tosylate, run SN2 with a nucleophile, then continue. Example: 1-pentanol → 1-bromopentane (PBr₃) → pentanenitrile (NaCN) → pentanoic acid (H₃O⁺/H₂O hydrolysis) — three carbon-functional transformations all initiated from an alcohol.

5. Microscale operations and SDS for alcohol chemistry (CLO 8)

Alcohols are generally less hazardous than alkyl halides, but the reagents used to react them are often dangerous. Special hazards include conc. H₂SO₄ (extremely corrosive), PCC and Cr(VI) reagents (carcinogenic), sodium metal (reacts violently with water), and tosyl chloride (lachrymator). The following microscale techniques apply:

Boiling point determination

Alcohols have characteristic high b.p. due to H-bonding (e.g., ethanol 78 °C, 1-propanol 97 °C, 1-butanol 117 °C). Microscale b.p. on a Thiele tube confirms identity.

Refractive index n_D²⁰

Alcohol n_D values increase modestly with chain length (ethanol 1.3614, 1-butanol 1.3993). Measured on Abbé refractometer to ±0.001.

Density and water solubility

Lower alcohols (≤ C4) are fully water-soluble; longer-chain alcohols are sparingly soluble or insoluble. Density of pure alcohols increases from ~0.79 (ethanol) towards 1.0 g/mL with chain length (1-decanol = 0.829).

Recrystallisation of solid alcohols

Solid alcohols (e.g., long-chain or aromatic) are recrystallised from polar protic solvents like ethanol-water mixtures. Purity confirmed by sharp m.p. The melting range should be no more than ~2 °C wide.

Disposal: alcohols themselves go to the non-halogenated organic solvent waste container. Acid waste from dehydrations must be neutralised first. Cr(VI)-containing oxidation waste is hazardous and must be reduced to Cr(III) before disposal as a heavy-metal aqueous waste.

Instructions

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

Section I — Structure & Naming (CLO 1, 2). Eight alcohol 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 — Reactions Bench (CLO 5). Twelve reactions covering dehydration, halogenation (HX, PBr₃, SOCl₂), oxidation (PCC, Jones), and Williamson ether synthesis. Predict the operative mechanism and the major product.

Section III — Synthesis Design (CLO 7). Six retrosynthesis problems involving alcohol formation and conversion. Choose reagent sequences that achieve the required regiochemistry and stereochemistry.

Section IV — SDS & Microscale Workbench (CLO 8). SDS interpretation for four reagents (PCC, conc. H₂SO₄, sodium metal, TsCl); microscale data matching for five alcohols; theoretical and percent yield calculations for two complete experiments.

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

Safety note: Conc. H₂SO₄ is a strong dehydrating acid that causes severe burns. PCC and other Cr(VI) reagents are suspected carcinogens. Sodium metal reacts violently with water and air moisture. Tosyl chloride is a strong lachrymator. In a real lab, work in the fume hood with PPE. 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°), and (c) R/S configuration if a stereocentre is present.

Score: 0 / 24

For each reaction, predict (a) the major product type and (b) the specific product. Apply your knowledge of dehydration, halogenation, and oxidation chemistry.

Score: 0 / 24

Six retrosynthesis problems. 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 alcohol chemistry. Answer the four questions per reagent.

SDS score: 0 / 16

Round 2 — Microscale data matching

Five microscale records — match each to the correct alcohol.

Candidate compounds (each used exactly once):

Methanol — colourless liquid, b.p. 65 °C, n_D²⁰ = 1.3284, density 0.792 g/mL
Ethanol — colourless liquid, b.p. 78 °C, n_D²⁰ = 1.3614, density 0.789 g/mL
1-Butanol — colourless liquid, b.p. 117 °C, n_D²⁰ = 1.3993, density 0.810 g/mL
2-Methyl-2-propanol (t-butanol) — colourless solid below 25 °C, m.p. 25–26 °C, b.p. 82 °C, n_D²⁰ = 1.3878
Cyclohexanol — colourless viscous liquid, m.p. 25 °C, b.p. 161 °C, n_D²⁰ = 1.4641, density 0.962 g/mL

Microscale score: 0 / 5

Round 3 — Theoretical and percent yield

Calculate yields for three alcohol-related 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). Give the IUPAC name of (CH₃)₂CHCH(OH)CH₃ and identify the class (1°/2°/3°). What is the hybridisation and bond angle at the carbon bearing OH?

Question 2 — CLO 2 (stereochemistry). 2,3-Butanediol has three stereoisomers. Two are enantiomers, one is meso. Identify which configuration is meso and explain why it is achiral.

Question 3 — CLO 5 (mechanism). 2-Methyl-2-butanol is heated with conc. H₂SO₄. What is the major product, and by what mechanism? Why is rearrangement not an issue here?

Question 4 — CLO 5 (oxidation). 1-Butanol is treated with (a) PCC and (b) Jones reagent (CrO₃/H₂SO₄). Predict the product in each case and explain why they differ.

Question 5 — CLO 7 (synthesis). Propose a synthesis of butyl ethyl ether (CH₃CH₂CH₂CH₂-O-CH₂CH₃) from 1-butanol and ethanol. Use the Williamson method.

Question 6 — CLO 8 (lab skills). A student dehydrates 3.70 g of 2-butanol (M.W. 74.12) with conc. H₂SO₄ and isolates 1.85 g of 2-butene (M.W. 56.11). Calculate the percent yield. (Hint: 1:1 stoichiometry.)

Example Lab Report

Sample report demonstrating the expected ACS-style format.

Alcohols: Structure, Stereochemistry, Mechanism, and Synthesis

Submitted by: [Student Name]

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

Abstract

This comprehensive lab examined alcohol chemistry through structure, stereochemistry, mechanism, and synthesis. Eight alcohols were named using IUPAC conventions and classified by substrate type. Twelve reactions were analysed to predict products of dehydration, halogenation, oxidation, and Williamson ether synthesis. Six retrosynthesis problems combined alcohol-forming reactions (hydration of alkenes, hydroboration-oxidation) with alcohol-using reactions (oxidation, conversion to halide, ether synthesis). SDSs for PCC, conc. H₂SO₄, sodium metal, and tosyl chloride were interpreted for hazards, PPE, and disposal. Microscale physical-property data for five alcohols were matched to literature values. Theoretical and percent yields were calculated for the dehydration of 2-butanol (achieved 66% yield) and the PCC oxidation of 1-pentanol to pentanal (achieved 81%).

Introduction

Alcohols are pivotal organic functional groups: their O-H proton is mildly acidic (pK_a ≈ 16), their oxygen is nucleophilic, and their C-O bond can be activated for substitution and elimination. This combination enables alcohols to serve as both nucleophiles (in Williamson ether synthesis or with acid chlorides) and as electrophiles after suitable activation (HX → R-X; PBr₃ → R-Br; SOCl₂ → R-Cl; TsCl/MsCl → tosylate/mesylate). Predicting reactivity requires knowing the substrate class, the reagent type, and any potential for carbocation rearrangement. This lab tested all four areas through structural drawing, stereochemical assignment, mechanism prediction, multi-step synthesis design, and microscale handling.

Reagents and Hazards (drawn from SDS)

Reagent	Major hazard	PPE	Key §9 data	Disposal
Conc. H₂SO₄	Severe burns; H290, H314	Goggles, gloves, lab coat, fume hood	Colourless oily liquid; density 1.84 g/mL	Dilute slowly into water (NEVER reverse), neutralise with NaHCO₃, then aqueous waste
PCC (pyridinium chlorochromate)	Suspected carcinogen (Cr VI); H350, H314	Goggles, double gloves, lab coat, fume hood	Orange crystalline solid	Reduce Cr(VI) to Cr(III) with FeSO₄, then heavy-metal hazardous waste
Sodium metal (Na)	Reacts violently with water (H260); pyrophoric	Goggles, gloves, fume hood, NO water near	Soft silvery metal; stored under mineral oil; m.p. 98 °C	Quench small amounts with isopropanol (slow), then water, then aqueous waste
Tosyl chloride (TsCl)	Lachrymator; H315, H318, H335	Goggles, gloves, lab coat, fume hood mandatory	White crystalline solid; m.p. 65–69 °C	Hydrolyse in aqueous NaOH (slow), then aqueous waste
PBr₃	Reacts violently with water; corrosive (H314, H330)	Goggles, gloves, fume hood; dry conditions	Colourless fuming liquid; density 2.85	Quench dropwise with cold water in fume hood, then aqueous waste
NaH (60% in mineral oil)	Reacts violently with water (H260); flammable	Goggles, gloves, fume hood; dry, inert atmosphere	Grey oil suspension	Quench cautiously with isopropanol, then water, aqueous waste

Results — Section I: Structure and Naming

Cmpd	IUPAC name	Class	Stereocentre
A	methanol	special (no C neighbours)	None
B	ethanol	1°	None
C	propan-2-ol (isopropanol)	2°	None (two CH₃ identical)
D	2-methylpropan-2-ol (t-butanol)	3°	None (three CH₃ identical)
E	(R)-butan-2-ol	2°	R at C2
F	3-methylbutan-2-ol	2°	R or S at C2 (2D drawing ambiguous)
G	cyclohexanol	2°	None (mirror plane through ring)
H	(R)-1-phenylethanol	1° benzylic / 2° depending on count	R at C1

Results — Section II: Reaction Predictions

#	Substrate	Reagent	Mechanism	Product
1	2-methyl-2-butanol	conc. H₂SO₄, heat	E1	2-methyl-2-butene (Zaitsev)
2	1-butanol	conc. H₂SO₄, heat	E1/E2 (high T)	1-butene (with some 2-butene from carbocation rearrangement)
3	(R)-2-butanol	PBr₃	SN2-like	(S)-2-bromobutane (inversion)
4	(R)-2-butanol	SOCl₂ + pyridine	SN2 (with pyridine)	(S)-2-chlorobutane (inversion)
5	(R)-2-butanol	SOCl₂ alone (no base)	SNi	(R)-2-chlorobutane (retention)
6	1-pentanol	PCC, CH₂Cl₂	Two-electron oxidation	pentanal (1° → aldehyde, no overoxidation)
7	1-pentanol	Jones reagent (CrO₃/H₂SO₄)	Successive oxidations	pentanoic acid (1° → carboxylic acid)
8	2-butanol	PCC	Two-electron oxidation	2-butanone (2° → ketone)
9	t-butanol	PCC or Jones	None (no α-H on OH carbon)	No reaction
10	1-butanol	NaH; then CH₃I	Williamson ether synthesis (SN2)	1-methoxybutane (butyl methyl ether)
11	1-pentanol	TsCl, pyridine	Substitution at S (no C inversion yet)	1-pentyl tosylate (then ready for SN2 by any Nu)
12	2-methyl-2-butanol	HCl, conc.	SN1 (3° alcohol)	2-chloro-2-methylbutane

Theoretical and Percent Yield

Experiment 1 — 2-butanol → 2-butene (E1 dehydration):

3.70 g of 2-butanol (M.W. 74.12) = 0.0499 mol. Stoichiometry 1:1. Theoretical mass 2-butene (M.W. 56.11) = 0.0499 × 56.11 = 2.80 g. Mass isolated = 1.85 g. Percent yield = 66.0%. Losses are typical for E1 dehydrations (carbocation can also undergo nucleophilic attack by water, giving back the starting alcohol; volatile alkene can escape during distillation).

Experiment 2 — 1-pentanol → pentanal (PCC oxidation):

2.00 g of 1-pentanol (M.W. 88.15) = 0.0227 mol. Theoretical mass pentanal (M.W. 86.13) = 0.0227 × 86.13 = 1.955 g. Mass isolated = 1.58 g. Percent yield = 80.8%. Excellent yield; PCC stops cleanly at the aldehyde without overoxidation to the acid.

Discussion

PCC vs Jones for 1° alcohol oxidation. The most striking comparison in this lab is entries 6 and 7 of Section II: 1-pentanol with PCC gives the aldehyde (pentanal), but with Jones reagent gives the carboxylic acid (pentanoic acid). The mechanistic basis: aqueous Jones generates an aldehyde hydrate (geminal diol) that is itself a kind of "alcohol" and is further oxidised. PCC operates in dichloromethane (anhydrous), so the aldehyde hydrate cannot form, and oxidation stops at the aldehyde. Choosing the right oxidant is essential for a clean synthesis.

3° alcohols are inert to oxidation. Entry 9 (t-butanol + PCC or Jones) gives no reaction because there is no α-H on the OH-bearing carbon. Without an α-H to remove, the standard chromium-based mechanism (proton abstraction from the alkoxychromate ester) cannot proceed.

SOCl₂ stereochemistry depends on conditions. Entries 4 and 5 illustrate a beautiful subtlety: SOCl₂ + pyridine gives clean SN2 with inversion at the alcohol carbon (pyridine deprotonates the chlorosulfite intermediate and traps Cl⁻, which then attacks from the back). SOCl₂ alone goes through SNi (concerted intramolecular substitution): Cl⁻ ends up on the same face as the original O–H, giving retention. The student can choose which stereochemistry to obtain by adding or omitting pyridine.

Williamson ether synthesis strategy. Entry 10 shows the right way to make an unsymmetrical ether: the more substituted side becomes the alkoxide (NaH on 1-butanol → 1-butoxide), and the less substituted side becomes the alkyl halide (CH₃I). The opposite combination would fail because attempting SN2 with a 3° alkyl halide gives elimination instead.

Yield analysis. The 66% yield for the 2-butanol dehydration is consistent with literature values; competition with reverse hydration and volatility of the alkene product limit the achievable yield. The 81% PCC oxidation yield is excellent for an aldehyde synthesis — losses were primarily mechanical (transfers, residual solvent).

Conclusions

All five CLOs covered in this lab were addressed. CLO 1 was demonstrated through correct IUPAC names and class assignments for all eight alcohols. CLO 2 was demonstrated through R/S assignments and the recognition of meso compounds. CLO 5 was demonstrated through correct mechanism predictions for all twelve reactions. CLO 7 was demonstrated through six successful retrosynthesis solutions. CLO 8 was demonstrated through correct interpretation of four SDSs, accurate matching of microscale data to literature values, and successful yield calculations.

References

1. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed., Oxford University Press, 2012, Ch. 17, 28.
2. Smith, M. B. March's Advanced Organic Chemistry, 8th ed., Wiley, 2020, Ch. 16, 17.
3. Sigma-Aldrich Safety Data Sheets, accessed online March 2026.

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 (CH₃CH₂)₂C(OH)CH₃. Identify hybridisation and bond angle at C-OH.

Hint: 3-methylpentan-3-ol; 3° (the OH-bearing C has three C neighbours); sp³, ~109.5°.

Practice 2 — CLO 1 + 2

2-Pentanol has how many stereocentres? Are (R)- and (S)-2-pentanol enantiomers, diastereomers, or constitutional isomers? Will their boiling points differ?

Hint: One stereocentre (C2). They are enantiomers; identical b.p. and most physical properties; opposite optical rotation.

Practice 3 — CLO 5 (dehydration)

3-Methyl-2-butanol is heated with conc. H₂SO₄. The major product is 2-methyl-2-butene, NOT 3-methyl-1-butene. Explain in terms of mechanism and rearrangement.

Hint: The initial 2° carbocation (at C2) undergoes a 1,2-hydride shift from C3 to give the more stable 3° carbocation (at C3). E1 deprotonation then gives the more substituted alkene (Zaitsev) — 2-methyl-2-butene. The "no rearrangement" product 3-methyl-1-butene is minor.

Practice 4 — CLO 5 (oxidation)

Predict the product of: (a) 2-pentanol + PCC; (b) 2-pentanol + Jones; (c) cyclohexanol + PCC; (d) 2-methyl-2-pentanol + PCC.

Hint: (a) 2-pentanone (PCC oxidises 2° to ketone, no further change). (b) 2-pentanone (Jones also stops at ketone for 2° alcohols — only 1° goes further). (c) cyclohexanone. (d) No reaction (3° alcohol, no α-H on OH carbon).

Practice 5 — CLO 5 (stereochemistry)

(R)-2-pentanol is treated with: (a) HCl; (b) PBr₃; (c) SOCl₂ + pyridine; (d) TsCl, then NaCN. Predict the stereochemistry of the major product in each case.

Hint: (a) HCl on 2° alcohol → mostly SN1 → racemic 2-chloropentane. (b) PBr₃ → SN2-like inversion → (S)-2-bromopentane. (c) SOCl₂ + pyridine → SN2 inversion → (S)-2-chloropentane. (d) TsCl makes the tosylate (no inversion at carbon); then NaCN does SN2 with one inversion → (S)-2-cyanopentane.

Practice 6 — CLO 7 (synthesis)

Design a synthesis of methyl propyl ether (CH₃-O-CH₂CH₂CH₃) from methanol and 1-propanol. State the operative mechanism in each step.

Hint: Williamson — pick the smaller alkyl halide (CH₃I from methanol) and the bigger alkoxide (1-propoxide from 1-propanol). Step 1: 1-propanol + NaH → sodium 1-propoxide. Step 2: + CH₃I → methyl propyl ether (SN2 at methyl is unhindered). The opposite pairing (methoxide + 1-bromopropane) also works but is slightly less favourable because the methyl is so small.

Practice 7 — CLO 7 (multi-step)

Starting from 1-butanol, propose a synthesis of pentanoic acid (one extra carbon). Use SN2 chemistry to add the carbon.

Hint: Three steps. (1) 1-butanol + PBr₃ → 1-bromobutane. (2) + NaCN/DMSO → pentanenitrile (SN2 adds the cyanide carbon). (3) + H₃O⁺/H₂O, heat (or NaOH/H₂O then H₃O⁺) → pentanoic acid (nitrile hydrolysis).

Practice 8 — CLO 8 (SDS)

A student plans to use sodium metal (Na) for a Williamson synthesis. Before opening the bottle, the student reads the SDS. State (a) the most serious hazard, (b) the required PPE, (c) why it is stored under mineral oil, (d) the proper way to dispose of leftover Na.

Hint: (a) Reacts violently with water (H260) — explosive H₂ release; pyrophoric on moist air. (b) Goggles, gloves, lab coat, fume hood, NO water nearby. (c) Mineral oil isolates Na from atmospheric moisture; without it, Na reacts with water vapour and oxygen, forming NaOH and Na₂O. (d) Quench cautiously with isopropanol (slow reaction with the bulky 2° alcohol), then dilute with water, then dispose as aqueous waste.

Practice 9 — CLO 8 (microscale)

A student isolates a colourless liquid product. The b.p. observed is 78.5 °C and the refractive index n_D²⁰ measured on an Abbé refractometer is 1.3618. The candidates from the synthesis are ethanol (b.p. 78.4 °C, n_D²⁰ = 1.3614) and methanol (b.p. 65 °C, n_D²⁰ = 1.3284). Which is the product?

Hint: Ethanol — both measurements match within microscale precision (b.p. ±0.5 °C, n_D ±0.001). Methanol is excluded by both (b.p. off by 13 °C, n_D off by 0.033).

Practice 10 — CLO 8 (yield)

A student converts 4.50 g of 1-butanol (M.W. 74.12) to 1-bromobutane (M.W. 137.02) using PBr₃. The PBr₃ → R-Br reaction is 1:1. After workup, 6.85 g of 1-bromobutane is isolated. Calculate the percent yield.

Hint: moles 1-butanol = 4.50 / 74.12 = 0.0607 mol; theoretical mass 1-bromobutane = 0.0607 × 137.02 = 8.32 g; % yield = 6.85 / 8.32 × 100 = 82.3%.