Radical — remote C–H functionalization
Barton nitrite ester reaction
How the Barton nitrite ester 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: Alkyl nitrite R–O–N=O (from ROH + NOCl, pyridine), hν (> 300 nm). Conditions: Benzene or toluene, 0–25 °C, photolysis. Bonds formed: O–H; C–N (nitroso → C=N–OH oxime); bonds broken: O–NO; remote C–H. Stereochemistry: Chair-like six-membered TS: only the δ-carbon on the same face is functionalised. Rate and selectivity: 1,5-HAT is far faster than intermolecular H abstraction.
At a glance
Step 1: Photolysis of the nitrite
Photolysis of an alcohol's nitrite ester homolyzes the weak O–NO bond, generating an alkoxy radical directly on the original alcohol oxygen — a reactive, high-energy radical eager to abstract a hydrogen atom from somewhere nearby.
Step 2: 1,5-Hydrogen atom transfer
Rather than reacting with whatever's closest in solution, the alkoxy radical abstracts a hydrogen specifically through a rigid, six-membered cyclic transition state — a 1,5-hydrogen atom transfer (1,5-HAT) — reaching a carbon four atoms away with remarkable geometric precision, regardless of that carbon's ordinary reactivity.
Step 3: Recombination with NO, then tautomerisation
The resulting carbon radical recombines with NO (released nearby) to form a new C–nitroso group, which tautomerizes to an oxime — this 1,5-HAT relay is a landmark strategy for functionalizing an otherwise completely unreactive C–H bond based purely on its distance from the original oxygen, not on any inherent chemical activation.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- TS
- Transition state. The highest-energy point on the pathway between two minima; it cannot be isolated.
- HAT
- Hydrogen-atom transfer. A radical abstracts H• from a C–H or X–H bond.
- hν
- Light. Photochemical activation.
How it compares with related reactions
| Barton nitrite ester reaction | Hunsdiecker reaction | Sandmeyer reaction | |
|---|---|---|---|
| Reagents | Alkyl nitrite R–O–N=O (from ROH + NOCl, pyridine), hν (> 300 nm) | RCOOAg (dry), Br₂ | ArN₂⁺ Cl⁻, CuCl (cat.) |
| Conditions | Benzene or toluene, 0–25 °C, photolysis | CCl₄, reflux, anhydrous | Aqueous HCl, 0–60 °C |
| Stereochemistry | Chair-like six-membered TS: only the δ-carbon on the same face is functionalised | Radical at carbon: stereochemistry lost | Not applicable (sp² aryl) |
| Rate / selectivity | 1,5-HAT is far faster than intermolecular H abstraction | Radical chain; Ag salt must be dry | Radical-chain / redox cycle; N₂ loss drives it |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Barton nitrite ester reaction?
Alkyl nitrite R–O–N=O (from ROH + NOCl, pyridine), hν (> 300 nm). Conditions: Benzene or toluene, 0–25 °C, photolysis.
Which bonds are formed and which are broken?
Formed: O–H; C–N (nitroso → C=N–OH oxime). Broken: O–NO; remote C–H.
What is the stereochemical outcome?
Chair-like six-membered TS: only the δ-carbon on the same face is functionalised
What controls the rate or the selectivity?
1,5-HAT is far faster than intermolecular H abstraction
Study guides that help with this reaction
- Carbonyl chemistry: addition, acyl substitution and enolates
- Radical chain reactions: initiation, propagation and termination
- Curved-arrow notation: rules and the mistakes students make