2,2-Dimethyl-1,3-dioxan-5-one

Chemical Properties

clear yellow liquid

Uses

2,2-Dimethyl-1,3-dioxan-5-one is used in the preparation of 2,2-dimethyl-[1,3]dioxan-5-ol by reducing with lithium aluminum hydride. It is also used in the annulation of bete-(hetero)aryl-alfa-nitro-alfa,beta-enals.

Synthesis

The general procedure for the synthesis of 2,2-dimethyl-1,3-dioxan-5-one from 5-amino-2,2-dimethyl-1,3-dioxan-5-methanol was as follows: first, 2,2-dimethoxypropane (21.5 mL, 175 mmol) and p-toluenesulfonic acid monohydrate (1.58 g, 7.93 mmol) were added to a solution of tris(hydroxymethyl)aminomethane ( 25.2 g, 159 mmol) in a solution of N,N-dimethylformamide (DMF, 180 mL). The reaction mixture was stirred at room temperature for 22 hours. After completion of the reaction, the mixture was diluted with ethyl acetate and neutralized with the addition of triethylamine. Subsequently, the solvent was concentrated under reduced pressure to remove the solvent and the crude product obtained was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate, 5:1) to afford 2,2-dimethyl-5-amino-5-hydroxymethyl-1,3-dioxane (20.9 g, 78% yield) as a colorless solid. The structure of this intermediate was confirmed by 1H NMR (400 MHz, CDCl3): δ 3.80 (d, J = 12.0 Hz, 2H), 3.60 (d, J = 12.0 Hz, 2H), 3.53 (s, 2H), 2.61 (s, 2H), 1.45 (s, 3H), 1.41 (s, 3H). Next, the above intermediate (10.2 g, 62.1 mmol) was dissolved in water (60 mL) and potassium dihydrogen phosphate (KH2PO4, 8.51 g, 621 mmol) was added. An aqueous solution of sodium periodate (NaIO4) (0.5 M, 125 mL, 63 mmol) was slowly added dropwise at 0 °C. After completion of the dropwise addition, the reaction mixture was stirred for 1 h at room temperature. After completion of the reaction, the product was extracted with dichloromethane and the organic layer was washed sequentially with 5% aqueous sodium thiosulfate and saturated saline and dried over anhydrous sodium sulfate. Finally, the solvent was removed by concentration under reduced pressure to afford the target compound 2,2-dimethyl-1,3-dioxan-5-one (7.35 g, 91% yield) as a colorless oil. Its structure was confirmed by 1H NMR (400 MHz, CDCl3): δ 4.15 (s, 4H), 1.45 (s, 6H).

References

[1] Australian Journal of Chemistry, 2001, vol. 54, # 12, p. 769 - 776
[2] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 21, p. 5891 - 5901
[3] Helvetica Chimica Acta, 2003, vol. 86, # 7, p. 2458 - 2470
[4] Synthesis, 1998, # 6, p. 879 - 882
[5] Canadian Journal of Chemistry, 1995, vol. 73, # 10, p. 1616 - 1626