Table 1 Summary of the reagents and conditions tested for the superacid-mediated Friedel–Crafts methylation of acetanilide

From: Leveraging long-lived arenium ions in superacid for meta-selective methylation

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Entry

Methylating reagent

T (°C)

t (h)

Yield (%)a

Isomer ratio (%)b

para

meta

1

MeOTf (1 equiv.)

−40

2

61

43

57

2

MeOTf (1 equiv.)

−20

2

79

25

75

3

MeOTf (1 equiv.)

0

2

83

<5

>95

4

Me3PO4 (0.33 equiv.)

0

2

81

<5

>95

5

Me2SO4 (1 equiv.)

0

2

90

<5

>95

  1. Key experiments for the optimization of the title reaction (full description of methylating reagents and conditions screening in SI). Reactions performed in an equivolumetric mixture of HF/SbF5.
  2. aYield of 1 determined by 1H NMR analysis using p-anisaldehyde as internal standard.
  3. bDetermined by 1H NMR analysis of crude product.
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