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Buchwald–Hartwig amination: p-Toluidine → 4-ethyl-N-(4-methylphenyl)aniline

84% yield, run at 60 °C for 16 hours, as recorded by experimental reaction archive. The written procedure is below. One of 861 recorded runs making this product; all of them are compared below.

verified record, 84% 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

CCCCCCNCCCCCCCCCI
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—
Reactant1-Ethyl-4-iodobenzeneC₈H₉I—
Reagent2-tert-Butyl-1,1,3,3-tetramethylguanidineC₉H₂₁N₃—
Reagent3-MethylisoxazoleC₄H₅NO—
CatalystAdBrettPhosC₅₆H₇₁F₃NO₅PPdS—
SolventDimethyl SulfoxideC₂H₆OS—
SolventDimethyl SulfoxideC₂H₆OS—
SolventDimethyl SulfoxideC₂H₆OS—
SolventDimethyl SulfoxideC₂H₆OS—
SolventDimethyl SulfoxideC₂H₆OS—
Product4-ethyl-N-(4-methylphenyl)anilineC₁₅H₁₇N83.94%

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

  • 84% of 4-ethyl-N-(4-methylphenyl)aniline.

Every recorded run making this product

861 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; 1-Bromo-4-ethylbenzenet-BuXPhosMTBD 25; 3-Methylisoxazole-5-carboxylic acid ethyl ester5 × Dimethyl Sulfoxide60 °C16 hours87%
p-Toluidine; 1-Ethyl-4-iodobenzeneAdBrettPhosMTBD 25; 3-Methylisoxazole-5-carboxylic acid ethyl ester5 × Dimethyl Sulfoxide60 °C16 hours86%
p-Toluidine; 1-Bromo-4-ethylbenzeneAdBrettPhosMTBD 255 × Dimethyl Sulfoxide60 °C16 hours85%
p-Toluidine; 1-Ethyl-4-iodobenzenet-BuXPhosMTBD 25; 3-Methylisoxazole-5-carboxylic acid ethyl ester5 × Dimethyl Sulfoxide60 °C16 hours85%
p-Toluidine; 1-Ethyl-4-iodobenzenet-BuBrettPhosMTBD 255 × Dimethyl Sulfoxide60 °C16 hours84%
p-Toluidine; 1-Ethyl-4-iodobenzeneAdBrettPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours84% (this run)
p-Toluidine; 1-Bromo-4-ethylbenzenet-BuXPhosMTBD 255 × Dimethyl Sulfoxide60 °C16 hours84%
p-Toluidine; 1-Bromo-4-ethylbenzenet-BuXPhos2,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-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours83%
p-Toluidine; 1-Ethyl-4-iodobenzenet-BuBrettPhosMTBD 25; 4-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours83%
p-Toluidine; 1-Bromo-4-ethylbenzeneAdBrettPhos2,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 hours83%
p-Toluidine; 1-Bromo-4-ethylbenzenet-BuXPhosMTBD 25; 3-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours83%
p-Toluidine; 1-Ethyl-4-iodobenzeneAdBrettPhosMTBD 25; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours83%
p-Toluidine; 1-Ethyl-4-iodobenzeneAdBrettPhos2,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 hours83%
p-Toluidine; 1-Ethyl-4-iodobenzenet-BuBrettPhosMTBD 25; 3-Methylisoxazole-5-carboxylic acid ethyl ester5 × Dimethyl Sulfoxide60 °C16 hours83%
p-Toluidine; 1-Ethyl-4-iodobenzeneAdBrettPhosMTBD 25; 3-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours83%
p-Toluidine; 1-Bromo-4-ethylbenzeneAdBrettPhos2,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-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours82%
p-Toluidine; 1-Ethyl-4-iodobenzenet-BuXPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; Ethyl 5-methylisoxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours82%
p-Toluidine; 1-Bromo-4-ethylbenzenet-BuBrettPhosMTBD 255 × Dimethyl Sulfoxide60 °C16 hours82%
p-Toluidine; 1-Bromo-4-ethylbenzenet-BuXPhosMTBD 25; Isoxazole, 5-phenyl-5 × Dimethyl Sulfoxide60 °C16 hours82%
p-Toluidine; 1-Ethyl-4-iodobenzeneAdBrettPhosMTBD 255 × Dimethyl Sulfoxide60 °C16 hours81%
p-Toluidine; 1-Ethyl-4-iodobenzenet-BuBrettPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours81%
p-Toluidine; 1-Bromo-4-ethylbenzeneAdBrettPhosMTBD 25; Ethyl 5-methylisoxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours81%
p-Toluidine; 1-Ethyl-4-iodobenzenet-BuXPhosMTBD 25; 4-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours81%
p-Toluidine; 1-Ethyl-4-iodobenzenet-BuXPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours81%
p-Toluidine; 1-Ethyl-4-iodobenzeneAdBrettPhosMTBD 25; Isoxazole, 5-phenyl-5 × Dimethyl Sulfoxide60 °C16 hours81%
p-Toluidine; 1-Ethyl-4-iodobenzenet-BuXPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; 3-Methylisoxazole-5-carboxylic acid ethyl ester5 × Dimethyl Sulfoxide60 °C16 hours81%
p-Toluidine; 1-Ethyl-4-iodobenzenet-BuBrettPhosMTBD 25; Ethyl 5-methylisoxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours81%
p-Toluidine; 1-Ethyl-4-iodobenzeneAdBrettPhosMTBD 25; Ethyl 5-methylisoxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours81%
p-Toluidine; 1-Bromo-4-ethylbenzeneAdBrettPhosMTBD 25; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours81%
p-Toluidine; 1-Bromo-4-ethylbenzenet-BuXPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours81%
p-Toluidine; 1-Ethyl-4-iodobenzenet-BuBrettPhosMTBD 25; Ethyl 1,2-oxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours81%
p-Toluidine; 1-Bromo-4-ethylbenzeneAdBrettPhosMTBD 25; 3-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours80%
p-Toluidine; 1-Ethyl-4-iodobenzenet-BuXPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; 3-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours80%
p-Toluidine; 1-Bromo-4-ethylbenzenet-BuBrettPhosMTBD 25; Ethyl 1,2-oxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours80%
p-Toluidine; 1-Bromo-4-ethylbenzenet-BuXPhosMTBD 25; 4-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours80%
p-Toluidine; 1-Ethyl-4-iodobenzenet-BuBrettPhosMTBD 25; 3,5-Dimethylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours80%
p-Toluidine; 1-Bromo-4-ethylbenzeneAdBrettPhos2,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-tetramine5 × Dimethyl Sulfoxide60 °C16 hours80%
p-Toluidine; 1-Bromo-4-ethylbenzenet-BuBrettPhosMTBD 25; Ethyl 5-methylisoxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours80%
p-Toluidine; 1-Ethyl-4-iodobenzenet-BuXPhosMTBD 25; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours80%
p-Toluidine; 1-Bromo-4-ethylbenzenet-BuBrettPhosMTBD 25; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours79%

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-f91db80d077d4f88a5c7ef12a5e08433). Open the source and check it against what is on this page.

  • experimental reaction archive record ord-f91db80d077d4f88a5c7ef12a5e08433 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.

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