Amine dealkylation
Von Braun reaction
How the Von Braun reaction works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: BrCN (cyanogen bromide). Conditions: CH₂Cl₂ or CHCl₃, 0–60 °C; then optional hydrolysis. Bonds formed: N–CN; C–Br (alkyl bromide); bonds broken: C–N (one alkyl); C–Br (of BrCN). Stereochemistry: Inversion at the carbon attacked by Br⁻ (SN2). Rate and selectivity: SN2 step selects Me > Et > other alkyl; benzyl and allyl cleave fastest.
At a glance
Step 1: Amine attacks BrCN
Cyanogen bromide's electrophilic carbon is attacked by a tertiary amine's nitrogen lone pair, forming a quaternary-like ammonium intermediate.
Step 2: Br⁻ attacks an N-alkyl group (SN2)
Bromide, freed in that step, performs a backside SN2 attack on one of the nitrogen's alkyl groups, cleaving that C–N bond and displacing a neutral cyanamide.
Step 3: Alkyl bromide + cyanamide
The result: one alkyl group is removed from the amine as an alkyl bromide, while the rest of the nitrogen is left as a disubstituted cyanamide — a way to selectively demethylate or de-ethylate a tertiary amine.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- Me
- Methyl. –CH₃.
- Et
- Ethyl. –CH₂CH₃.
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- SN2
- Bimolecular nucleophilic substitution. One concerted step with backside attack and inversion; rate = k[RX][Nu].
How it compares with related reactions
| Von Braun reaction | Catalytic reduction of a nitro group to an amine | Cope elimination | |
|---|---|---|---|
| Reagents | BrCN (cyanogen bromide) | ArNO₂, H₂ (1–5 atm), 5–10% Pd/C or PtO₂ | H₂O₂ or mCPBA (oxidation); then heat |
| Conditions | CH₂Cl₂ or CHCl₃, 0–60 °C; then optional hydrolysis | EtOH or EtOAc, 25–60 °C | Oxidation 0–25 °C; elimination 80–160 °C (milder in DMSO/THF) |
| Stereochemistry | Inversion at the carbon attacked by Br⁻ (SN2) | No stereocentre; usually chemoselective for NO₂ over aryl C–Cl only with care | Syn elimination via planar 5-membered TS |
| Rate / selectivity | SN2 step selects Me > Et > other alkyl; benzyl and allyl cleave fastest | Highly exothermic; hydroxylamine can accumulate if catalyst is poisoned | Intramolecular, first order; faster in polar aprotic solvents |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Von Braun reaction?
BrCN (cyanogen bromide). Conditions: CH₂Cl₂ or CHCl₃, 0–60 °C; then optional hydrolysis.
Which bonds are formed and which are broken?
Formed: N–CN; C–Br (alkyl bromide). Broken: C–N (one alkyl); C–Br (of BrCN).
What is the stereochemical outcome?
Inversion at the carbon attacked by Br⁻ (SN2)
What controls the rate or the selectivity?
SN2 step selects Me > Et > other alkyl; benzyl and allyl cleave fastest
Study guides that help with this reaction
- SN1, SN2, E1 or E2? How to decide which mechanism wins
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go