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Buchwald–Hartwig amination: p-Toluidine → 2-Pyridinamine, N-(4-methylphenyl)-

93% yield, run at 60 °C for 16 hours, as recorded by experimental reaction archive. The written procedure is below. One of 862 recorded runs making this product; all of them are compared below.

verified record, 93% yield recorded, Not balanced as written, From experimental reaction archive

Reagents, catalysts and solvents are in the table below.

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The atoms, from reactants to products

CCCCCNCCCCCNCCBr
Reactants · 1/6
breakingformingbond order changesmapped atom that changes

Drawn from the record's atom map: which bonds break and which form between the reactants and products the source listed. It shows a change in connectivity, not a simulated trajectory and not a mechanism.

What was in the flask

RoleSpeciesFormulaYield
Reactantp-ToluidineC₇H₉N—
Reactant2-BromopyridineC₅H₄BrN—
ReagentMTBD 25C₈H₁₅N₃—
ReagentIsoxazole, 5-phenyl-C₉H₇NO—
Catalystt-BuXPhosC₄₂H₅₅F₃NO₃PPdS—
SolventDimethyl SulfoxideC₂H₆OS—
SolventDimethyl SulfoxideC₂H₆OS—
SolventDimethyl SulfoxideC₂H₆OS—
SolventDimethyl SulfoxideC₂H₆OS—
SolventDimethyl SulfoxideC₂H₆OS—
Product2-Pyridinamine, N-(4-methylphenyl)-C₁₂H₁₂N₂92.91%

The equation does not balance as written. That is usual for an experimental record: the source listed what it put in and what it measured, not a stoichiometric equation.

Conditions

Temperature
60 °C
Duration
16 hours

Only the dimensions the source stated are listed. Anything absent here was not recorded, and it is not inferred from what the class usually needs.

Yield

  • 93% of 2-Pyridinamine, N-(4-methylphenyl)-.

Every recorded run making this product

862 runs of this class made the same product. The 40 highest-yielding are listed; this page's run is among them.

ReactantsCatalystReagentsSolventTemp.TimeYield
p-Toluidine; 2-Iodopyridinet-BuXPhosMTBD 25; 4-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours100%
p-Toluidine; 2-Iodopyridinet-BuBrettPhosMTBD 25; 4-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours100%
p-Toluidine; 2-Iodopyridinet-BuXPhosMTBD 25; 3-Methylisoxazole-5-carboxylic acid ethyl ester5 × Dimethyl Sulfoxide60 °C16 hours100%
p-Toluidine; 2-IodopyridineAdBrettPhosMTBD 25; 3-Methylisoxazole-5-carboxylic acid ethyl ester5 × Dimethyl Sulfoxide60 °C16 hours99%
p-Toluidine; 2-Iodopyridinet-BuBrettPhosMTBD 25; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours99%
p-Toluidine; 2-Iodopyridinet-BuBrettPhosMTBD 25; Ethyl 5-methylisoxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours98%
p-Toluidine; 2-Iodopyridinet-BuBrettPhosMTBD 255 × Dimethyl Sulfoxide60 °C16 hours98%
p-Toluidine; 2-Iodopyridinet-BuBrettPhosMTBD 25; 3-Methylisoxazole-5-carboxylic acid ethyl ester5 × Dimethyl Sulfoxide60 °C16 hours98%
p-Toluidine; 2-Iodopyridinet-BuXPhosMTBD 25; Isoxazole, 5-phenyl-5 × Dimethyl Sulfoxide60 °C16 hours98%
p-Toluidine; 2-Bromopyridinet-BuXPhosMTBD 25; 3-Methylisoxazole-5-carboxylic acid ethyl ester5 × Dimethyl Sulfoxide60 °C16 hours97%
p-Toluidine; 2-Bromopyridinet-BuBrettPhosMTBD 25; 3-Methylisoxazole-5-carboxylic acid ethyl ester5 × Dimethyl Sulfoxide60 °C16 hours97%
p-Toluidine; 2-IodopyridineAdBrettPhosMTBD 25; Ethyl 1,2-oxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours96%
p-Toluidine; 2-IodopyridineAdBrettPhosMTBD 25; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours96%
p-Toluidine; 2-IodopyridineAdBrettPhosMTBD 25; Ethyl 5-methylisoxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours96%
p-Toluidine; 2-BromopyridineAdBrettPhosMTBD 25; 3-Methylisoxazole-5-carboxylic acid ethyl ester5 × Dimethyl Sulfoxide60 °C16 hours96%
p-Toluidine; 2-Iodopyridinet-BuXPhosMTBD 255 × Dimethyl Sulfoxide60 °C16 hours95%
p-Toluidine; 2-Iodopyridinet-BuXPhosMTBD 25; 3-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours95%
p-Toluidine; 2-IodopyridineAdBrettPhosMTBD 25; Isoxazole, 5-phenyl-5 × Dimethyl Sulfoxide60 °C16 hours95%
p-Toluidine; 2-Bromopyridinet-BuXPhosMTBD 255 × Dimethyl Sulfoxide60 °C16 hours94%
p-Toluidine; 2-IodopyridineAdBrettPhos2,N'3,N'3,N3,N3,N'5,N'5,N5,N5-nonamethyl-2,4,6-triaza-3lambda5,5lambda5-diphosphaocta-3,5-diene-3,3,5,5-tetramine; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours94%
p-Toluidine; 2-IodopyridineAdBrettPhosMTBD 25; 3-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours94%
p-Toluidine; 2-IodopyridineAdBrettPhosMTBD 25; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours94%
p-Toluidine; 2-Iodopyridinet-BuXPhosMTBD 25; Ethyl 5-methylisoxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours94%
p-Toluidine; 2-Iodopyridinet-BuXPhosMTBD 25; 5-Phenyl-1,2,4-oxadiazole5 × Dimethyl Sulfoxide60 °C16 hours94%
p-Toluidine; 2-BromopyridineAdBrettPhosMTBD 25; Ethyl 1,2-oxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours94%
p-Toluidine; 2-Bromopyridinet-BuXPhosMTBD 25; Ethyl 5-methylisoxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours93%
p-Toluidine; 2-Bromopyridinet-BuXPhosMTBD 25; 4-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours93%
p-Toluidine; 2-Bromopyridinet-BuBrettPhosMTBD 25; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours93%
p-Toluidine; 2-Bromopyridinet-BuBrettPhosMTBD 255 × Dimethyl Sulfoxide60 °C16 hours93%
p-Toluidine; 2-Bromopyridinet-BuXPhosMTBD 25; Isoxazole, 5-phenyl-5 × Dimethyl Sulfoxide60 °C16 hours93% (this run)
p-Toluidine; 2-Iodopyridinet-BuBrettPhos2,N'3,N'3,N3,N3,N'5,N'5,N5,N5-nonamethyl-2,4,6-triaza-3lambda5,5lambda5-diphosphaocta-3,5-diene-3,3,5,5-tetramine; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours93%
p-Toluidine; 2-BromopyridineAdBrettPhosMTBD 25; 3-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours93%
p-Toluidine; 2-Iodopyridinet-BuBrettPhosMTBD 25; 3-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours92%
p-Toluidine; 2-Bromopyridinet-BuXPhosMTBD 25; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours92%
p-Toluidine; 2-IodopyridineAdBrettPhosMTBD 25; 3-Methoxy-5-carbethoxy-isoxazole5 × Dimethyl Sulfoxide60 °C16 hours92%
p-Toluidine; 2-Iodopyridinet-BuBrettPhosMTBD 25; Isoxazole, 5-phenyl-5 × Dimethyl Sulfoxide60 °C16 hours92%
p-Toluidine; 2-Iodopyridinet-BuXPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; 3-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours92%
p-Toluidine; 2-Bromopyridinet-BuBrettPhos2,N'3,N'3,N3,N3,N'5,N'5,N5,N5-nonamethyl-2,4,6-triaza-3lambda5,5lambda5-diphosphaocta-3,5-diene-3,3,5,5-tetramine; 3-Methylisoxazole-5-carboxylic acid ethyl ester5 × Dimethyl Sulfoxide60 °C16 hours92%
p-Toluidine; 2-Iodopyridinet-BuXPhosMTBD 25; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours92%
p-Toluidine; 2-Chloropyridinet-BuXPhosMTBD 25; 3-Methylisoxazole-5-carboxylic acid ethyl ester5 × Dimethyl Sulfoxide60 °C16 hours91%

Every value is as the source recorded it. A run with no yield was reported without one, and nothing here is averaged, modelled or filled in.

Procedure

Copied from the source record, unedited

These solutions were added to a 384- well source plate (80 µL per well). The Mosquito HTS liquid handling robot was used to dose each of these solutions (200 nL each) into a 1536-well plate.

The source

This record comes from experimental reaction archive (ord-da87755b25fc48c99ea22973b3f822c4). Open the source and check it against what is on this page.

  • experimental reaction archive record ord-da87755b25fc48c99ea22973b3f822c4 from dataset "Ahneman" (doi: 10.1126/science.aar5169). No atom mapping is provided by the source.

    experimental record · quality high · source

experimental reaction record.

How to read this record

This is one experiment, not a rule. It says that on one occasion these species were combined under these conditions and this came out. It does not say the reaction will give the same result on your substrate, and nothing on the page has been generalised into a claim that it would.

The pathway is a separate question, kept on separate pages. A mechanism here is the canonical arrow pushing for a class, run on real structures and labelled rule-derived. It is not evidence, and this record is not a mechanism.

Where to next

More Buchwald–Hartwig amination records

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