Table 1. Optimization of N,O-Acetal-Forming Reaction between Salicylaldehyde and THIQ.
| entry | 7, mmol | THIQ, mmol | additive (equiv) | solvent (M) | T, °C | t, h | yield of 2f, % | yield of 12, % |
|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 1 | − | PhMe (0.25) | rt | 48a | 35 | 36 |
| 2 | 2 | 1 | PhCO2H (0.2) | PhMe (0.25) | rt | 18 | 38 | 48 |
| 3 | 1.1 | 1 | PhCO2H (0.2) | PhMe (0.25) | rt | 24 | 54 | 25 |
| 4 | 1.1 | 1 | 2-EHAb (0.2) | PhMe (0.25) | rt | 24 | 62 | 21 |
| 5 | 1 | 1.1 | 2-EHA (0.2) | PhMe (0.25) | rt | 48a | 38 | trace |
| 6 | 1 | 1.1 | 2-EHA (0.2) | DMF (0.25) | rt | 48a | 23 | trace |
| 7 | 1 | 1.1 | 2-EHA (0.2) | EtOH (0.25) | rt | 48a | 22 | 31 |
| 8 | 1 | 1.1 | 2-EHA (0.2) | MeCN (0.25) | rt | 48a | 62 | 32 |
| 9 | 1 | 1.1 | 2-EHA (1.3) | PhMe (0.25) | rt | 48a | 75 | trace |
| 10 | 1 | 1.3 | 2-EHA (1.3) | PhMe (0.25) | rt | 48 | 94 | trace |
| 11 | 1 | 1.3 | 2-EHA (1.3) | PhMe (0.25) | 60 | 1.5 | 95 | trace |
| 12 | 1 | 1.3 | 2-EHA (1.3) | PhMe (0.1) | 60 | 3 | 97 | − |
| 13c | 1 | 1.3 | 2-EHA (1.3) | PhMe (0.1) | 60 | 6a | 64 | − |
| 14 | 1 | 1.3 | AcOH (1.3) | PhMe (0.1) | 60 | 3 | 98 | − |
| 15 | 1 | 1.3 | AcOH (0.2) | PhMe (0.1) | 60 | 3 | 59 | − |
| 16 | 1 | 1.3 | AcOH (1.0) | PhMe (0.1) | 60 | 3 | 98 | − |
a
Reaction incomplete.
b
2-EHA = 2-ethylhexanoic acid.
c
No molecular sieves.