Table 1. Optimization of Reaction Conditions for Iodination of Arylhydrazines with Iodinea.
| entry | I2 (mmol) | additive (mmol) | solvent (mL) | yieldb (%) |
|---|---|---|---|---|
| 1g | 0.5 | Cs2CO3 (0.5) | DMSO (1.5) | 63, 43c, 57d |
| 2 | 0.5 | Cs2CO3 (0.5) | DMF (1.5) | 50 |
| 3 | 0.5 | Cs2CO3 (0.5) | DMA (1.5) | 38 |
| 4 | 0.5 | Cs2CO3 (0.5) | CH3CN (1.5) | 35 |
| 5 | 0.5 | Cs2CO3 (0.5) | acetone (1.5) | 29 |
| 6 | 0.5 | Cs2CO3 (0.5) | MeOH (1.5) | 28 |
| 7 | 0.5 | Cs2CO3 (0.5) | CHCl3 (1.5) | 13 |
| 8 | 0.5 | Cs2CO3 (0.5) | toluene (1.5) | 14 |
| 9 | 1.0 | Cs2CO3 (0.5) | DMSO (1.5) | 61 |
| 10 | 0.5 | Cs2CO3 (0.5) | DMSO (0.5) | 68 |
| 11 | 0.5 | Cs2CO3 (0.5) | DMSO (0.25) | 58 |
| 12 | 0.5 | Cs2CO3 (0.75) | DMSO (0.5) | 36 |
| 13 | 0.5 | none | DMSO (0.5) | 54 |
| 14h | 1.0 | none | DMSO (0.5) | 84, 83e, 78f |
| 15 | 1.0 | none | DMSO (0.1) | 92 |
| 16 | 0.5 | none | DMSO (0.1) | 92 (87) |
| 17 | 0.3 | none | DMSO (0.1) | 82 |
a
Conditions: 1a, I2, additive, and solvent were stirred at 60 °C for 6 h in the air.
b
Determined by 1H NMR using an internal standard 1,3,5-trioxane (isolated yield).
c
Reaction temperature was 40 °C.
d
Reaction temperature was 80 °C.
e
Reaction time was 4 h.
f
Reaction time was 8 h.
g
In this reaction, azide and aniline, besides aryl iodide, were generated as byproducts. After the reaction, arylhydrazine was already consumed but I2 was not consumed. Most probably, air acted as an oxidant for this iodination.
h
Iodine not only acts as iodination reagent but also oxidizes phenylhydrazines to diazonium salt, and therefore excessive iodine is more beneficial to the iodination.