Isomerisation of aldoses in pyridine in the presence of aluminium oxide Dag Ekeberg, Svein Morgenlie * and Yngve Stenstrøm Department of Chemistry, Biotechnology and Food Science, Section Chemistry, Agricultural University of Norway, PO Box 5003, N-1432 A ˚ s, Norway Received 17 September 2004; accepted 3 December 2004 Available online 13 January 2005 Abstract—Addition of aluminium oxide to boiling pyridine solutions of D-xylose, L-arabinose, D-mannose and D-glucose strongly increased the reaction rate of the aldose–ketose transformation. The maximum content of 2-ketose was reached after less than 2 h forthealdopentosesand3hforthealdohexoses. D-threo-2-Pentulose (xylulose) was prepared from D-xylose,andisolatedasits O- isopropylidenederivative,theyieldwasnearlytwicethatcomparedtothatusuallyobtainedintheclassicalLobrydeBruyn–Alberda van Ekenstein transformation in pyridine. Ó 2004 Elsevier Ltd. All rights reserved. Keywords: Aldoses; 2-Ketoses; D-threo-2-Pentulose; Isomerisation; Pyridine; Aluminium oxide 1.Introduction The introduction in 1927 of pyridine both as a solvent and a base represented an important improvement of the Lobry de Bruyn–Alberda van Ekenstein aldose–ke- tose transformations. 1 When these reactions are carried out in alkali hydroxide solution, extensive isomerisation and retro aldol reactions occur, 2 and in addition, acids are formed. After prolonged reaction time, more than 50 compounds have been observed in the product mix- ture from D-glucose and aqueous calcium hydroxide. 3 Review articles of the Lobry de Bruyn–Alberda van Ekenstein reaction have been published by Speck 4 and Angyal. 5 Inpyridine,thereactionsoccurringarelimited to aldose–ketose transformations and epimerisations, and some rare or otherwise unavailable ketoses have been prepared from aldoses by isomerisation in boiling pyridine. The yields in these reactions are generally low, but much of the unreacted starting material may in several cases be recovered by crystallisation, 6–8 and yields are therefore often calculated from the amount of aldose consumed. One reason for the low yields is that the equilibrium seldom is reached due to sluggish reaction, typical reaction times reported, ranging from about4–20h,areoftenfarfromenough,butprolonged reaction is avoided in order to prevent extensive forma- tion of side products. For the pentoses, an additional reason for the low yields is that the ketose:aldose ratios atequilibriumarewellbelowone.Thisisduetothelower stabilityofthepentulosescomparedtothealdopentoses, since the former cannot exist in pyranose form. 5 In continuation of a previously reported work on aldol reactions, 9 we required D-threo-2-pentulose (xylu- lose) as a starting material. The pentulose may be pre- pared by several microbial and enzymatic methods, and it is, for example, formed by isomerisation of D-xy- lose. 4,10,11 Theyieldsarelowalsointheseenzymecatal- ysed isomerisation reactions, but despite the fact that theymaybeimprovedthroughstabilisationoftheprod- uctthroughcomplexformation, 12 amoresimple,chemi- cal method was preferable in our case. We have some experiences with aluminium oxide in wanted, as well as in unwanted isomerisation reactions, and it has found use as a catalyst, especially in hydrocarbon isomerisa- tions. 13,14 We therefore hoped to improve the aldose– ketose transformation in boiling pyridine of D-xylose 0008-6215/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.carres.2004.12.006 * Corresponding author. Tel.: +47 64 94 77 14; fax: +47 64 94 77 20; e-mail: svein.morgenlie@nlh.no Carbohydrate RESEARCH Carbohydrate Research 340 (2005) 373–377