Planning a synthesis

A synthesis question is a maze. Work backwards from the target, asking "what could have made this group?"

The core map:

• alkene → halogenoalkane — HBr
• alkene → alcohol — steam, H₃PO₄ catalyst
• halogenoalkane → alcohol — NaOH(aq), reflux
• halogenoalkane → alkene — NaOH in ethanol, reflux (elimination)
• halogenoalkane → nitrile — KCN in ethanol, reflux (+1 carbon)
• halogenoalkane → amine — excess ethanolic NH₃, sealed tube
• nitrile → amine — LiAlH₄ (or H₂/Ni)
• nitrile → carboxylic acid — dilute HCl(aq), reflux (hydrolysis)
• 1° alcohol → aldehyde → carboxylic acid — acidified K₂Cr₂O₇ (distil, then reflux)
• carbonyl → hydroxynitrile — HCN/KCN (+1 carbon)
• acid + alcohol → ester — conc H₂SO₄ catalyst

Chain length is the giveaway. If the target has one more carbon than the starting material, your route must pass through a nitrile (KCN) or a hydroxynitrile (HCN). Nothing else adds a carbon at this level.

Conversions and reagents

Tap a conversion on the left, then the reagents and conditions that achieve it.

Plan the route

Mass spectrometry

The peak at the highest m/z (ignoring isotope peaks) is the molecular ion, M⁺ — it gives the relative molecular mass directly.

Fragmentation gives the structure. Common fragment ions:

• m/z 15 = CH₃⁺ · m/z 29 = C₂H₅⁺ or CHO⁺ · m/z 43 = CH₃CO⁺ or C₃H₇⁺ · m/z 77 = C₆H₅⁺ (a phenyl group)
• A loss of 15 from M⁺ means a methyl group was lost; a loss of 29 means an ethyl or a CHO.

Isotope peaks are a gift:

• M+2 peak the same height as M (a 1 : 1 ratio) → bromine present (⁷⁹Br and ⁸¹Br are roughly equally abundant).
• M+2 peak one third the height of M (a 3 : 1 ratio) → chlorine present (³⁵Cl : ³⁷Cl ≈ 3 : 1).
• A small M+1 peak comes from the 1.1% of ¹³C.

Your turn — the molecular ion

Your turn — the fragment

Read the isotope pattern

Infrared spectroscopy

A bond absorbs IR radiation at a wavenumber that depends on the bond strength and the masses of the atoms — so each functional group has a characteristic absorption.

• O–H (alcohol) — broad, 3200–3600 cm⁻¹
• O–H (carboxylic acid) — very broad, 2500–3300 cm⁻¹ (it often swamps the C–H peaks)
• N–H (amine or amide) — 3300–3500 cm⁻¹ (often a sharp double peak for a primary amine)
• C=O — strong and sharp, 1680–1750 cm⁻¹
• C≡N (nitrile) — 2200–2250 cm⁻¹ · C=C — 1620–1680 cm⁻¹

Argue from absence as well as presence. "A C=O at 1715 cm⁻¹ and no broad O–H below 3300" rules out the carboxylic acid and points to an aldehyde or ketone. The fingerprint region below 1500 cm⁻¹ is unique to each compound and is matched against a database.

Which functional group?

Tap a piece of spectroscopic evidence, then the functional group it points to.

Nuclear magnetic resonance

NMR detects nuclei with spin — ¹H and ¹³C. Chemical shifts (δ, in ppm) are measured against TMS (tetramethylsilane), set at δ = 0. TMS is used because it is inert, volatile, non-toxic and gives a single sharp peak well clear of everything else. Samples are dissolved in a solvent with no ¹H, such as CDCl₃.

¹³C NMR is the easy one: the number of peaks = the number of carbon environments. No splitting.

¹H NMR gives you three pieces of information:

• Chemical shift — where the peak is, telling you the environment. Roughly: alkyl δ 0.7–1.6 · next to a C=O δ ≈ 2.1 · next to an O δ 3.3–4.3 · aromatic δ 6.5–8.0 · aldehyde δ 9.3–10.5 · carboxylic acid δ 10–12.
• Integration — the relative area under each peak gives the ratio of protons in each environment.
• Splitting (the n + 1 rule) — a peak is split into n + 1 lines by the n equivalent protons on the adjacent carbon.

D₂O shake: the –OH and –NH protons exchange with deuterium, so their peak disappears from the spectrum. They also do not obey the n + 1 rule, appearing as broad singlets.

Your turn — ¹³C environments

Your turn — ¹H environments

Apply the n + 1 rule

Your turn — the n + 1 rule

Chromatography

All chromatography separates a mixture by the balance between a stationary phase and a mobile phase. A component that is more strongly adsorbed onto the stationary phase moves slowly; one that is more soluble in the mobile phase races ahead.

• TLC — stationary phase: silica or alumina on a plate. Measure the R_f value:

• Gas chromatography (GC) — a volatile sample is carried by an inert gas over a liquid stationary phase in a long column. Each component has a characteristic retention time. The area under each peak is proportional to the amount present.
• HPLC — a liquid mobile phase under high pressure; used for compounds that are non-volatile or heat-sensitive, such as drugs and proteins.
• GC-MS — the columns feed straight into a mass spectrometer, so each separated component is identified as well as separated. This is the workhorse of forensic and drugs testing.

Your turn — Rf value

Retention time

Put it all together

The big ideas to know

That is the whole of OA4. Press Finish to see your score.