A Practical and Cost-Effective Method for the Synthesis of Bicyclo[2.2.2]octane-1,4-dicarboxylic Acid

Abstract

A short and efficient synthesis of bicyclo[2.2.2]octane-1,4-dicarboxylic acid involving the formation of a semicarbazone is developed, and a reproducible protocol for the reduction of this semicarbazone is described. The use of microwaves significantly shortens the duration of the sequence to the diacid compared to the previously described synthetic method. In addition, by shifting from the use of large amounts of Raney nickel to a solid-phase process, both the safety and cost are improved notably.

Key words

bicyclo[2.2.2]octane-1,4-dicarboxylic acid - safe - semicarbazone - microwave irradiation - rigid backbone - solid-phase

• References

• 1 Baker FW, Parish RC, Stock LM. J. Am. Chem. Soc. 1967; 89: 5677
• 2 Ermer O, Dunitz JD. Chem. Commun. 1968; 567
• 3 Goldsmith RH, Vura-Weis J, Scott AM, Borkar S, Sen A, Ratner MA, Wasielewski MR. J. Am. Chem. Soc. 2008; 130: 7659
• 4 Honegger E, Heilbronner E, Hess N, Martin HD. Chem. Ber. 1987; 120: 187
• 5 Kaszynski P, Januszko A, Ohta K, Nagamine T, Potaczek P, Young VG, Endo Y. Liq. Cryst. 2008; 35: 1169
• 6 Lemouchi C, Mézière C, Zorina L, Simonov S, Rodríguez-Fortea A, Canadell E, Wzietek P, Auban-Senzier P, Pasquier C, Giamarchi T, Garcia-Garibay MA, Batail P. J. Am. Chem. Soc. 2012; 134: 7880
• 7 Li K, Lee J, Olson DH, Emge TJ, Bi W, Eibling MJ, Li J. Chem. Commun. 2008; 6123
• 8 Liu Y, Turner SR. J. Polym. Sci., Part A: Polym. Chem. 2010; 48: 2162
• 9 Ritchie CD, Lewis ES. J. Am. Chem. Soc. 1962; 84: 591
• 10 Ritchie CD, Megerle GH. J. Am. Chem. Soc. 1967; 89: 1452
• 11 Taimr L, Smith JG. J. Polym. Sci., Part A: Polym. Chem. 1971; 9: 1203
• 12 Von Gersdorff J, Kirste B, Niethammer D, Harrer W, Kurreck H. Magn. Reson. Chem. 1988; 26: 416
• 13 Yuen T, Danilovic D, Li K, Li J. J. Appl. Phys. 2008; 103: 07B725
• 14 Roberts JD, Moreland WT. Jr, Frazer W. J. Am. Chem. Soc. 1953; 75: 637
• 15 Wang Y. CN101709034A, 2010
• 16 Holtz HD, Stock LM. J. Am. Chem. Soc. 1964; 86: 5183
• 17 Wood G, Woo EP. Can. J. Chem. 1968; 46: 3713