Table 1 Investigation into the catalytic performance of amine 1a
| |||
|---|---|---|---|
Entry | Product | Notes | Product observed? |
1 |
| 1a produced and purified according to ref. 3; 16 h reaction time | Yes: 57% (1H NMR spectroscopy)a |
2 |
| 1a produced and purified according to ref. 3; 4 h reaction time | Yes: product peak observed by LC–MS |
3 |
| 1a produced and purified according to ref. 3; 16 h reaction time | Yes: >99% (1H NMR spectroscopy)a |
4 |
| 1a produced and purified according to ref. 3 and provided as a blind sample; 18 h, 90 °C | Yes: 98% isolated yield |
5 |
| 1a produced and purified according to ref. 3; 16 h reaction time. | Yes: 55% (1H NMR spectroscopy)a |
6 |
| 1a produced and purified according to ref. 3; 16 h reaction time | Yes: 49% (1H NMR spectroscopy)a |
7 |
| 1a produced and purified according to ref. 3; 16 h reaction time | Yes: 27% (1H NMR spectroscopy)a |
8 |
| 1a produced and purified according to ref. 3; 2 h reaction time. | Yes: GC–MS shows substantial (> 50%) product formation |
9 |
| As per entry 8, but solvent = o-xylene:H2O 4:1 | Yes: GC–MS shows almost quantitative product formation |
10 |
| 5 g of 4-bromoaniline scale, o-xylene:H2O (50:12), overnight | Yes: 98% isolated yield |
11 |
| 1a produced and purified according to ref. 3; 2 h reaction time | Yes: 1H NMR spectroscopyb 48% |
12 |
| As for entry 11, but with 1a further purified by a second round of column chromatography | Reduced: 1H NMR spectroscopyb 42% |
13 |
| Crude 1a reacted with PhB(OH)2 and K2CO3 before purificationc; catalytic conditions as per entry 3 | No: NMR spectroscopy and GC–MS show no product |
14 |
| Crude 1a reacted with PhB(OH)2 and K2CO3 before purificationc; catalytic conditions as per entry 5 | Minimal: 1H NMR spectroscopya shows 4% product |
15 |
| Crude 1a reacted with PhB(OH)2 and K2CO3 before purificationc; catalytic conditions as per entry 6 | No: NMR spectroscopy and GC–MS show no product |
16 |
| Crude 1a reacted with PhB(OH)2 and K2CO3 before purificationc; catalytic conditions as per entry 7 | Reduced: 1H NMR spectroscopya shows 16% product |
17 |
| 1a recycled from a large-scale reaction for entry 10 | No: product peak absent in GC–MS |
18 |
| 1a produced by Cu-catalysed Chan–Lam coupling; conditions identical to those of entry 3 | No: 1H NMR spectroscopy and GC–MS show no product |
19 |
| 1a produced by Cu-catalysed Chan–Lam and provided as a blind sample; conditions identical to those of entry 4 | No: 1H NMR spectroscopy shows no product |
20 |
| 1a produced by Cu-catalysed Chan–Lam coupling; conditions identical to those of entry 5 | No: 1H NMR spectroscopy and GC–MS show no product |
21 |
| 1a produced by Cu-catalysed Chan–Lam coupling; conditions identical to those of entry 6 | No: 1H NMR spectroscopy and GC–MS show no product |
22 |
| 1a produced by Cu-catalysed Chan–Lam coupling; conditions identical to those of entry 7 | No: 1H NMR spectroscopy and GC–MS show no product |
23 |
| 1a produced by Cu-catalysed Chan–Lam coupling; conditions identical to those of entry 2 | No: product peak absent in LC–MS |
24 |
| 1a produced by Fe-mediated reductive amination, conditions as per those of entry 9 | No: product peak absent in GC–MS |
25 |
| 1a produced using [Pd(PtBu3)2] as catalyst, conditions as per those of entry 9 | No: product peak absent in GC–MS |
26 |
| 1a produced and purified according to ref. 3; then further purified by recrystallization from ethyl acetate/hexane | No: 1H NMR spectroscopy shows no product |
