Table 3.
Optimization of the synthesis of PZ1 (8). a
| Entry | Reagent 1 (Equiv) | Reagent 2 (Equiv) | T (°C) | Solvent | 8, Yield (%) b |
|---|---|---|---|---|---|
| 1 | NHS (1) | DCC (1) | 25 | DMF | 21 |
| 2 | NHS (1) | DCC (1) | 60 | ChCl/gly | 16 |
| 3 | NHS (1) | DCC (1) | 60 | ChCl/PG | 30 |
| 4 | NHS (1) | DCC (1) | 60 | ChCl/urea | 13 |
| 5 | NHS (1) | DCC (1) | 60 | menthol/LA | NR c |
| 6 | NHS (1) | DCC (1) | 60 | d-fructose/urea | NR c |
| 7 | NHS (1) | DCC (1) | 60 | Bu4NBr/gly | 7 d |
| 8 | NHS (1) | DCC (1) | 60 | Bu4NCl/gly | 19 d |
| 9 | NHS (1) | - | 60 | ChCl/PG | <5 d |
| 10 | - | DCC (1) | 60 | ChCl/PG | NR c |
a Reaction conditions in DES: 1.0 g DES per 0.5 mmol of 4; DES: ChCl/gly (1:2 mol mol−1); ChCl/urea (1:2 mol mol−1); ChCl/PG (1:3 mol mol−1); d-fructose/urea (3:2 w/w); dl-menthol/LA (1:2 mol mol−1); Bu4NBr/gly (1:4 mol mol−1); Bu4NCl/gly (1:4 mol mol−1). b The yields reported are for isolated products. c No reaction. d Calculated via 1H-NMR analysis of the crude reaction mixture using an internal standard technique (NMR internal standard: dibromomethane).