GENERAL STEPS: The general procedure for the synthesis of methyl 3,5-diketohexanoate from methyl chloroformate and acetylacetone is as follows:
Step A. 3-Acylation of 2,4-pentanedione
Acetylacetone (1.00 g, 10 mmol) was added to a suspension of magnesium chloride (1.35 g, 1.2 eq.) in 20 mL of dichloromethane followed by pyridine (2.13 mL, 2.5 eq.). The mixture was stirred at 0 °C for 1 hour, then alkyl chloroformate or phenyl isocyanate (1.0 eq.) was slowly added dropwise at 0 °C. The reaction mixture was gradually warmed to room temperature over 8 hours, after which it was poured into aqueous 3N HCl (10 mL) and extracted with dichloromethane (20 mL). The organic layer was washed with brine (20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. Depending on the physical state of the product, distillation or recrystallization was chosen to purify it from the appropriate solvent.
Product Characterization:
1. 3-(Methoxycarbonyl)acetylacetone: colorless liquid, yield 68.1%. Distillation conditions: 45°C, 0.5 mmHg. ESI (-ve) MS m/z 157.1 [M-H]-. 1H NMR (DMSO-d6, 300MHz): δ 2.999 (s, 6H), 3.730 (s, 3H), 17.760 (s, 1H).
2. 3-(Ethoxycarbonyl)acetylacetone: colorless liquid, yield 60.5%. Distillation conditions: 60°C, 1.4 mmHg. ESI (-ve) MS m/z 171.2 [M-H]-. 1H NMR (DMSO-d6, 300MHz): δ 1.253 (t, 3H), 2.303 (s, 6H), 4.164-4.236 (m, 2H), 17.747 (s, 1H).
3. 3-(phenylaminocarbonyl)acetylacetone: white solid, yield 72.0%, melting point 118-119°C. ESI (-ve) MS m/z 218.1 [M-H]-. 1H NMR (DMSO-d6, 300MHz): δ 2.154 (s, 6H), 7.084 (t, 1H), 7.324 (t, 2H), 7.640 (d, J = 8.1Hz, 2H), 10.355 (s, 1H), 16.463 (s, 1H).
