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Nitrogen-extrusion rearrangement family

Schmidt reaction

How the Schmidt reaction works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.

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In short. A 3-step mechanism. Typical reagents: HN₃ (or NaN₃), H₂SO₄ or polyphosphoric acid. Conditions: Strong acid, 25–80 °C; HN₃ is toxic and explosive. Bonds formed: R–N; N=C=O; N₂; bonds broken: C–OH; C–R (migrates); N–N₂. Stereochemistry: Migrating group retains configuration. Rate and selectivity: N₂ loss and R-shift are concerted and irreversible.

At a glance

ReagentsHN₃ (or NaN₃), H₂SO₄ or polyphosphoric acid
Solvent / conditionsStrong acid, 25–80 °C; HN₃ is toxic and explosive
Bonds formedR–N; N=C=O; N₂
Bonds brokenC–OH; C–R (migrates); N–N₂
StereochemistryMigrating group retains configuration
Rate / selectivityN₂ loss and R-shift are concerted and irreversible

Step 1: HN₃ adds, water leaves

+H⁺H⁺, −H₂O+ROOHNHNNROHOHNNNROHOHNNNROHNNNOH₂1 · HN₃ ADDS, WATER LEAVEScarboxylic acidSUBSTRATEhydrazoic acidHN₃NUCLEOPHILEtetrahedral intermediateINTERMEDIATEtetrahedral intermediateINTERMEDIATEprotonated acyl azideCATIONwaterH₂OBYPRODUCTAcid-promoted addition–elimination converts C–OH into C–N₃.

A carboxylic acid is protonated by acid, then attacked by hydrazoic acid (HN₃), forming a tetrahedral intermediate that loses water to give an azidoacylium-type species.

Step 2: Loss of N₂, 1,2-shift

−N₂, −H⁺+ROHNNNRNONN2 · LOSS OF N₂, 1,2-SHIFTprotonated acyl azideCATIONisocyanateINTERMEDIATEdinitrogenN₂BYPRODUCTR shiftsSame migration as Curtius, with the acyl azide made in situ.

Loss of N₂ triggers the same concerted 1,2-migration seen throughout this family: the R group shifts from carbon to the adjacent nitrogen, forming an isocyanate.

Step 3: Hydrolysis and decarboxylation

+−CO₂+RNOOHHRNHOOHRNHOOHRNH₃OO3 · HYDROLYSIS AND DECARBOXYLATIONisocyanateELECTROPHILEwaterH₂ONUCLEOPHILEcarbamic acidINTERMEDIATEcarbamic acidINTERMEDIATEammonium (amine·H⁺)PRODUCTcarbon dioxideCO₂BYPRODUCTIn acid the amine is isolated as its ammonium salt.

Hydrolysis and loss of CO₂ deliver a primary amine — the fourth member of the Hofmann/Curtius/Lossen/Schmidt family, all converging on identical isocyanate chemistry from four completely different starting functional groups.

Abbreviations and terms

R
R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
H2
Hydrogen gas. Reductant for catalytic hydrogenation.
H2SO4
Sulfuric acid. Strong acid and dehydrating agent.
Hofmann
Hofmann product/rule. Elimination giving the less substituted alkene (bulky base or leaving group).

How it compares with related reactions

Schmidt reactionHofmann rearrangementLossen rearrangement
ReagentsHN₃ (or NaN₃), H₂SO₄ or polyphosphoric acidBr₂, NaOH (or NaOBr), H₂OHydroxamic acid, activator (Ac₂O, TsCl), base
ConditionsStrong acid, 25–80 °C; HN₃ is toxic and explosive0 °C then 50–70 °CMild base, 25–100 °C, then H₂O
StereochemistryMigrating group retains configurationMigrating group retains configurationMigrating group retains configuration
Rate / selectivityN₂ loss and R-shift are concerted and irreversibleConcerted 1,2-shift is rate-determining; amine has one carbon fewerRate set by leaving-group ability of the O-acyl/O-sulfonyl group

Test yourself

Try to answer each question before opening it.

Which reagents and conditions are typical for the Schmidt reaction?

HN₃ (or NaN₃), H₂SO₄ or polyphosphoric acid. Conditions: Strong acid, 25–80 °C; HN₃ is toxic and explosive.

Which bonds are formed and which are broken?

Formed: R–N; N=C=O; N₂. Broken: C–OH; C–R (migrates); N–N₂.

What is the stereochemical outcome?

Migrating group retains configuration

What controls the rate or the selectivity?

N₂ loss and R-shift are concerted and irreversible

Study guides that help with this reaction

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