Uses
Lactonization of olefins with monomethyl ester of malonic acid and ceric ammonium nitrate was carried out in acetic acid and in acetonitrile under simple mechanical stirring or ultrasound irradiation. Lactonization of olefins with CAN and monomethyl ester of malonic acid under ultrasound irradiation shows an acceleration with respect to the analogous mechanically stirred reaction.
Synthesis
The general procedure for the synthesis of monomethyl malonate from dimethyl malonate is as follows:
1. In a 1 L single neck flask equipped with a magnetic stirrer, 158.33 g (1.2 mol) of dimethyl malonate was added and 10 μL of acetonitrile was added to dissolve the dimethyl malonate.
2. The solution was stirred for 1 minute and then the reaction mixture was cooled to 0°C using an ice water bath.
3. 100 mL of water was added to the mixture and stirring was continued for 30 minutes.
4. 240 mL of a 5M KOH aqueous solution (1.2 mol) was added dropwise while using a dispensing funnel to complete the dropwise addition in 15 minutes (20 mL of 0.5 M oxalic acid was used to titrate the 5M KOH solution; oxalic acid was purchased from Mallinckrodt Company, Hazelwood, MO).
5. After the titration was complete, the reaction mixture continued to be stirred for 60 minutes, during which time the flask was covered with a stopper and kept in an ice water bath.
6. Upon completion of the reaction, the reaction mixture was acidified with 150 mL of aqueous 12M HCl in an ice water bath and subsequently saturated with NaCl.
7. Using a 1L dispensing funnel, the acidified mixture was extracted with five 500mL portions of ethyl acetate.
8. The ethyl acetate extracts were combined and washed with 500mL of saturated aqueous NaCl.
9. The ethyl acetate extract was dried with about 100 g of anhydrous sodium sulfate.
10. After removing the desiccant by gravity filtration, the ethyl acetate solution was concentrated using a rotary evaporator.
11. Distillation was carried out at 2.5 mmHg under reduced pressure and the fraction with a boiling point of 91-92 °C was collected to give monomethyl malonate as a colorless oil.
12. The product was recovered at 45 °C in a yield of 114.77 g (81%) containing 4% dimethyl malonate and 1% malonic acid.
Note: Examples 26-36 were prepared using the same procedure as Example 37, but the reaction conditions were adjusted according to Table 4 below.
References
[1] Tetrahedron Letters, 2008, vol. 49, # 28, p. 4434 - 4436
[2] Chemical and Pharmaceutical Bulletin, 2009, vol. 57, # 5, p. 508 - 510
[3] Patent: WO2008/150487, 2008, A2. Location in patent: Page/Page column 14-17
[4] Patent: WO2008/150487, 2008, A2. Location in patent: Page/Page column 16-17
[5] Patent: WO2008/150487, 2008, A2. Location in patent: Page/Page column 16-17
