Buchwald–Hartwig amination: 4-Bromo-2-nitrotoluene → 1-(4-Methyl-3-nitrophenyl)piperazine
39% yield, run at 110 °C, as recorded by experimental reaction archive. The written procedure is below.
The atoms, from reactants to products
What was in the flask
| Role | Species | Formula | Yield |
|---|---|---|---|
| Reactant | 4-Bromo-2-nitrotoluene | C₇H₆BrNO₂ | |
| Reactant | Piperazine | C₄H₁₀N₂ | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | Binap, (A+-)- | C₄₄H₃₂P₂ | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | Toluene | C₇H₈ | |
| Product | 1-(4-Methyl-3-nitrophenyl)piperazine | C₁₁H₁₅N₃O₂ | 39.25% |
Conditions
- Temperature
- 110 °C
Yield
- 39% of 1-(4-Methyl-3-nitrophenyl)piperazine.
Other recorded runs with the same starting material
No other run in the library makes this product. These runs of the same class start from one of the same reactants, which is the nearest company this record has.
- tert-butyl N-[2-chloro-5-(piperazin-1-yl)phenyl]carbamate57%
- 1-(2,2-Difluoro-2H-1,3-benzodioxol-5-YL)piperazine51%
- 4-(2-Fluoro-4-methylphenylamino)-7-(piperazin-1-yl)cinnoline-3-carbonitrile51%
- 1-(2-Chlorophenyl)piperazine44%
- 1-(Pyridin-3-yl)piperazine0%
- 4-Piperazin-1-yl-1-benzofuran-2-carboxamide0%
- 4-Chloro-2-(piperazin-1-yl)benzonitrile0%
- 4-Fluoro-2-(piperazin-1-yl)benzonitrile0%
Procedure
Copied from the source record, unedited
palladium(II) acetate (0.065 g, 0.29 mmol), BINAP (0.144 g, 0.23 mmol) and CS2CO3 (0.943 g, 2.89 mmol) were added to a mixture of 4-bromo-1-methyl-2-nitrobenzene (0.5 g, 2.31 mmol) and piperazine (1.623 g, 18.84 mmol) . The suspension were heated to 110 °C for 24 hours, LCMS showed product mass [M+1]: 222.1 at retension time RT=1.21 min (polar short purity method). Workup reaction by additional of water (10mL), extracted with EtOAc (3x20 mL), washed with brine, dried with Na2SO4, evaporated off solvent to give a residue, which was purified by isco chromatographer, eluting with 0-10% MeOH in DCM to give 1-(4-methyl-3-nitrophenyl)piperazine (0.201 g, 39.3 %) as a yellow solid.
The source
This record comes from experimental reaction archive (ord-7a7d88bb15974f808c2ac9e73fb46a04). Open the source and check it against what is on this page.
experimental reaction archive record ord-7a7d88bb15974f808c2ac9e73fb46a04 from dataset "750 AstraZeneca ELN dataset" (url: https://chemrxiv.org/engage/chemrxiv/article-details/60c9e3f37792a23bfdb2d471). No atom mapping is provided by the source.
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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