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Buchwald–Hartwig amination: p-Toluidine → 4-Methoxy-4'-methyldiphenylamine

59% yield, run at 60 °C for 16 hours, as recorded by experimental reaction archive. The written procedure is below. One of 864 recorded runs making this product; all of them are compared below.

verified record, 59% 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

COCCCCNCCCCCCCCCBr
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—
Reactant4-BromoanisoleC₇H₇BrO—
Reagent2-tert-Butyl-1,1,3,3-tetramethylguanidineC₉H₂₁N₃—
Reagentc1ccc(CN(Cc2ccccc2)c2ccon2)cc1C₁₇H₁₆N₂O—
CatalystAdBrettPhosC₅₆H₇₁F₃NO₅PPdS—
SolventDimethyl SulfoxideC₂H₆OS—
SolventDimethyl SulfoxideC₂H₆OS—
SolventDimethyl SulfoxideC₂H₆OS—
SolventDimethyl SulfoxideC₂H₆OS—
SolventDimethyl SulfoxideC₂H₆OS—
Product4-Methoxy-4'-methyldiphenylamineC₁₄H₁₅NO59.07%

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

  • 59% of 4-Methoxy-4'-methyldiphenylamine.

Every recorded run making this product

864 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; 4-IodoanisoleAdBrettPhosMTBD 25; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours68%
p-Toluidine; 4-Bromoanisolet-BuBrettPhosMTBD 25; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours68%
p-Toluidine; 4-BromoanisoleAdBrettPhosMTBD 25; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours67%
p-Toluidine; 4-Bromoanisolet-BuXPhosMTBD 25; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours66%
p-Toluidine; 4-IodoanisoleAdBrettPhos2,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; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours66%
p-Toluidine; 4-Iodoanisolet-BuBrettPhosMTBD 25; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours66%
p-Toluidine; 4-Bromoanisolet-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; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours66%
p-Toluidine; 4-BromoanisoleAdBrettPhos2,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; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours65%
p-Toluidine; 4-Iodoanisolet-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; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours64%
p-Toluidine; 4-Iodoanisolet-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; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours61%
p-Toluidine; 4-Iodoanisolet-BuBrettPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours60%
p-Toluidine; 4-IodoanisoleAdBrettPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours60%
p-Toluidine; 4-BromoanisoleAdBrettPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours59% (this run)
p-Toluidine; 4-Iodoanisolet-BuXPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours58%
p-Toluidine; 4-Bromoanisolet-BuXPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours58%
p-Toluidine; 4-Bromoanisolet-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; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours58%
p-Toluidine; 4-IodoanisoleAdBrettPhos2,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 hours58%
p-Toluidine; 4-Iodoanisolet-BuBrettPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours58%
p-Toluidine; 4-IodoanisoleAdBrettPhosMTBD 25; 3-Methylisoxazole-5-carboxylic acid ethyl ester5 × Dimethyl Sulfoxide60 °C16 hours58%
p-Toluidine; 4-Bromoanisolet-BuBrettPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours57%
p-Toluidine; 4-IodoanisoleAdBrettPhos2,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 hours57%
p-Toluidine; 4-Iodoanisolet-BuXPhosMTBD 25; C17H16N2O5 × Dimethyl Sulfoxide60 °C16 hours57%
p-Toluidine; 4-Iodoanisolet-BuXPhosMTBD 25; Ethyl 1,2-oxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours57%
p-Toluidine; 4-Iodoanisolet-BuXPhosMTBD 25; 4-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours56%
p-Toluidine; 4-Iodoanisolet-BuXPhosMTBD 255 × Dimethyl Sulfoxide60 °C16 hours56%
p-Toluidine; 4-Iodoanisolet-BuXPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; 4-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours55%
p-Toluidine; 4-BromoanisoleAdBrettPhosMTBD 25; Ethyl 5-methylisoxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours55%
p-Toluidine; 4-IodoanisoleAdBrettPhosMTBD 25; Ethyl 5-methylisoxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours55%
p-Toluidine; 4-Iodoanisolet-BuBrettPhosMTBD 25; Isoxazole, 5-phenyl-5 × Dimethyl Sulfoxide60 °C16 hours55%
p-Toluidine; 4-Bromoanisolet-BuXPhosMTBD 255 × Dimethyl Sulfoxide60 °C16 hours55%
p-Toluidine; 4-IodoanisoleAdBrettPhos2,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; Ethyl 5-methylisoxazole-3-carboxylate5 × Dimethyl Sulfoxide60 °C16 hours55%
p-Toluidine; 4-IodoanisoleAdBrettPhos2,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 hours55%
p-Toluidine; 4-IodoanisoleAdBrettPhosMTBD 255 × Dimethyl Sulfoxide60 °C16 hours55%
p-Toluidine; 4-Iodoanisolet-BuBrettPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours54%
p-Toluidine; 4-Iodoanisolet-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 hours54%
p-Toluidine; 4-BromoanisoleAdBrettPhosMTBD 25; 3-Phenylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours54%
p-Toluidine; 4-Iodoanisolet-BuXPhosMTBD 25; 3-Methylisoxazole-5-carboxylic acid ethyl ester5 × Dimethyl Sulfoxide60 °C16 hours54%
p-Toluidine; 4-BromoanisoleAdBrettPhosMTBD 255 × Dimethyl Sulfoxide60 °C16 hours53%
p-Toluidine; 4-IodoanisoleAdBrettPhos2-tert-Butyl-1,1,3,3-tetramethylguanidine; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours53%
p-Toluidine; 4-IodoanisoleAdBrettPhosMTBD 25; 3-Methylisoxazole5 × Dimethyl Sulfoxide60 °C16 hours53%

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-51f93556227b45ada0a6d5a5931d3412). Open the source and check it against what is on this page.

  • experimental reaction archive record ord-51f93556227b45ada0a6d5a5931d3412 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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