Table 1. Optimization of the Synthesis of 2-Methyl-1,8-naphthyridineab (10).
| entry | cat. (mol %) | solvent | temp. (°C) | time (h) | yield (%) |
| 1 | 50 | 10 | NR | ||
| 2 | H2O | 50 | 12 | NR | |
| 3 | acetone | 50 | 10 | NR | |
| 4 | ChOH(1) | acetone | 50 | 24 | 52 |
| 5 | ChOH(1) | H2O | 50 | 6 | 99 |
| 6 | ChOH (1) | H2O | rt | 22 | 90 |
| 7 | ChOH (0.5) | H2O | 50 | 12 | 95 |
| 8 | ChOH (0.5) | H2O | rt | 24 | 57 |
| 9 | NaOH | H2O | 50 | 6 | 88 |
| 10 | KOH | H2O | 50 | 6 | 84 |
| 11 | Et3N | H2O | 50 | 6 | NR |
| 12 | Et3N·(CH2OH)2c | H2O | 50 | 6 | NR |
Reaction condition: 2-aminonicotinaldehyde, 8 (0.5 mmol), and acetone, 9 (0.5 mmol) were stirred with ChOH (1 mol %) in H2O (1 mL).
Isolated yield, rt: room temperature NR: no reaction,.
1:1 mixture.
