The Kiliani reaction, i.e. the elongation of the carbon chain by means of cyanide addition to the carbonyl group of carbohydrate derivatives, is studied on lower C3-, C4- and C6-ketoses under continuous flow conditions. Depending on the process parameters, the corresponding cyanohydrins or α-hydroxycarboxylic acids are obtained. A simple on-line purification of the effluent is studied using cation exchange resins. Reactions provide high yields and selectivity within short residence times, emphasizing the assets of the continuous flow process versus the batch process.
1. Yu, H.; Ballard, C.E.; Boyle, P.D.; Wang, B. 2002 Tetrahedron 58 7663–7679.
2. (a) Kiliani, H. Ber. Dtsch. Chem. Ges. 1885, 18, 3066–3072; (b) Kiliani, H. Ber. Dtsch. Chem. Ges. 1886, 19, 221–227.
3. http://www.orgsyn.org/orgsyn/prep.asp?prep=cv4p0506. Accessed 4.10.2010.
4. (a) Hotchkiss, D.J.; Soengas, R.; Simone, M.I.; van Ameijde, J.; Hunter, S.; Cowley, A.R.; Fleet, G.W.J. Tetrahedron Lett. 2004, 45, 9461–9464; (b) Soengas, R.; Izumori, K.; Simone, M.I.; Watkin, D.J.; Skytte, U.P.; Soetaert, W.; Fleet, G.W.J. Tetrahedron Lett. 2004, 46, 5755–5759.
5. Wiles, C ; Watts., P. Micro Reaction Technology in Organic Synthesis; CRC Press Taylor & Francis: Boca Raton, FL 2011; pp xxii+432.
6. (a) Acke, D.R.J. Evaluation of Microreactor Technology for Multicomponent Reactions. Ph.D. thesis, Faculty of Bioscience Engineering, Ghent University, Ghent, 2007; (b) Acke, D.R.J.; Orru, R.V.A.; Stevens, C.V. QSAR Comb. Sci. 2006, 25, 474–483; (c) Acke, D.R.J.; Stevens, C.V. Green Chem. 2007, 9, 386–390; (d) Acke, D.R.J.; Stevens, C.V.; Roman, B.I. Org. Process Res. Dev. 2008, 12, 921–928; (e) Heugebaert, T.S.A.; Roman, B.I.; De Blieck, A.; Stevens, C.V. Tetrahedron Lett. 2010, 51, 4189–4191.
7. (a) Monbaliu, J.C.M.R.; Cukalovic, A.; Marchand-Brynaert, J.; Stevens, C.V. Tetrahedron Lett. 2010, 51, 5830–5833; (b) Monbaliu, J.C.M.R.; Winter, M.; Chevalier, B.; Schmidt, F.; Jiang, Y.; Hoogendoorn, R.; Kousemaker, M.A.; Stevens, C.V. Bioresource Technol. 2011, 102, 9304–9307.
8. Schwalbe, T.; Golbig K. et al. Eur. Pat. Appl. EP 1123734, 2001. Chem. Abstr. 2001, 135, 154468b.
9. http://www.thalesnano.com/products/x-cube. Accessed 21.10.2011.
10. http://www.cyanidecode.org/cyanide_environmental.php;Cummings, T.F. Occup. Med.-C 2004, 54, 82–85 (Safety measures). Accessed 21.10.2011.
11. Serianni, A.S.; Nunez, H.A.; Barker, R. 1980 J.Org. Chem. 45 3329–3341.
12. Sukata, K. 1987 Bull. Chem. Soc. Jpn. 60 3820–3822.
13. http://www.lancevalves.com/pdfs/corrosiondata.pdf. Accessed 2.10.2010.
14. Blazer, R.M.; Whaley, T.W.; Teller, E. 1980 J. Am. Chem. Soc 102 5082–5085.