Fructose dehydration reactions

Furan Derivatives Catalytic processes used to obtain furan derivatives from carbohydrates and the catalytic routes from furan intermediates to chemicals and polymers have been reviewed by Moreau et al. [27]. Some of the main reactions are summarized in Fig. 3.2. From fructose or carbohydrates based on fructose (sucrose, inulin), the first transformation step is dehydration to 5-hydroxy methylfur-fural (HMF). Fructose dehydration at 165 °C was performed in the presence of... 

D-glucose and D-fructose in acidified deuterium oxide, and acid conversion of D-[2- H]glucose were conducted, in order to determine the importance of 39 as an intermediate from the proportion of deuterium incorporated at C-3 of 5-(hydroxymethyl)-2-furaldehyde. However, the 2-furaldehyde formed in the reactions contained no deuterium. Thus, an essentially irreversible sequence that involves hexose, 36, 38, 40, and 11 best explains the acid-catalyzed, dehydration reaction. 

When allowed to react in an almost anhydrous medium (the only water being that produced during the dehydration reaction), compound 51 was found to form maltol (52) and isomaltol (16) in proportions varying with the reagents.88 In aqueous acidic solution, these products and acetylformoin (53) would all be expected from 50 or 51, dependent on whether or not the ring opened and the manner in which the opening occurred. The presence of 49 accounts for compounds 51, 52, 53, and 16, that are frequently detected as products of the degradation of D-fructose, particularly when amines are present. 

The interest in FDA arises from its possible application as a renewable-derived replacement for terephthalic acid in the manufacture of polyesters. A multitude of oxidation techniques has been applied to the conversion of HMF into FDA but, on account of the green aspect, platinum-catalyzed aerobic oxidation (see Fig. 8.35), which is fast and quantitative [191], is to be preferred over all other options. The deactivation of the platinum catalyst by oxygen, which is a major obstacle in large-scale applications, has been remedied by using a mixed catalyst, such as platinum-lead [192]. Integration of the latter reaction with fructose dehydration would seem attractive in view of the very limited stability of HMF, but has not yet resulted in an improved overall yield [193]. 

In acidic degradation, 1,2-enediol forms from the aldose or ketose after a series of dehydration reactions. If the initial sugar is a hexose, 1,2-enediol is converted to HMF. If it is a pentose, 1,2-enediol is converted to 2-furaldehyde. 3-Deoxyaldose-2-ene, 3-deoxyosulose, and osulos-3-ene are intermediates in the acidic degradation of fructose. The last series of reactions include both fragmentation reactions (flavor production) and polymerization reactions (color production). 

Fructose, one of the most common ketohexoses, readily dehydrates to afford HMF in the presence of Br0nsted acids in polar solvents. A variety of aprotic polar solvents, including DMSO, DMF, N,N-dimethylacetamide (DMA), and sulfolane, are used for these liquid-phase reaction because of the solubility of carbohydrates. A variety of solid acids, such as ion-exchange resins [156], zeolites [157, 158], metal oxides, and heteropoly acid salts, have been examined for HMF production from fructose [159,160]. Niobic acid, niobium phosphate, vanadium phosphate, sulfated zirconia, Amberlyst-15, and acid-functionalized mesoporous silicas are also found to exhibit high catalytic activity for fructose dehydration [161-167]. Moreover, soHd acid catalysts have also been examined in ionic liquids [168-175]. 

Brown DW, Floyd AJ, Kinsman RG, Roshan-Ali Y (1982) Dehydration reactions of fructose in non-aqueous media. J Chem Technol Biotechnol 32 920-924... 

All sugars with free reducing groups are very reactive. In mildly acidic solutions monosaccharides are stable, while disaccharides hydrolyze to yield monosaccharides. Fructose is maximally stable at pH 3.3 glucose at pH 4.0. At lower pH s dehydration reactions prevail, while the Lo-bry de Bruyn-van Ekenstein rearrangement oc-... 

We tested this reaction scheme in meat. Ten percent D-glucose was added to a beef extract and the pH was adjusted widi a 6 N hydrochloric acid or sodium hydroxide solution. Figure 4 shows the pH-dependence of M-1 and M-3 after 15 min heating at 121°C. As expected, 1,2-enolization and M-3 formation predominates below pH 4. Above pH 5 there is little M-3 formation, which explains why we never observed M-3 from heated meats (pH 5.4). There is a sharp decline in the M-1 yield above pH 10. This observation is consistent with the base-catalyzed fructose dehydration Shaw et al. investigated at pH 11.5 (45). They reported that M-1 was not formed at pH 11.5 however, if the alkalinity was not constantly maintained, M-1 was formed as the pH decreased. Similarly, when 1% D-ribose was added to the beef extract, formation of 2-furaldehyde dominated at low pH and M-2 formation became more impotant at pH above 4.5, which again explains why 2-furaldehyde was never observed in heated meats. The general reaction pathways for formation of the markers are summarized in Figure 5. 

In 1983, the first report on the conversion of fructose to 5-HMF in the presence of pyridinium chloride with 70% yield under mild reaction conditions (30 min, 120 °C) was published [30]. This sparked an interest in investigating the dehydration of fructose over molten salts. Twenty years later, in 2003, Lansalot-matras et al. revisited the field and investigated the acid-catalyzed dehydration of fructose in commercially available ionic liquids, ([BMIM][BF4]) and ([BMIM][PF6]) with DMSO as co-solvent in the presence of Amberlyst-15 [31]. They demonstrated the advantages of using ILs as solvents and reported a yield of 80% for 5-HMF in 24 h and at a relatively low temperature of 80°C compared to that employed in the previous method. However, conventional methods require much higher temperatures of 100 to 300°C [31]. In an effort to further improve the dehydration reaction, the following reaction p>arameters were studied extensively with promising results ... 

Sucrose is unstable at temperatures albO C (320T) and thermolyzes to the brown candy that we appreciate as caramel. Caramel contains a myriad of decomposition products formed by simultaneous cleavage of sucrose to glucose and fructose, dehydrations, fragmentations (such as retroaldol additions), isomerizations through enols (apply the last three reactions to glucose and see what you get), and polymerizations. Two of the odorants that have been identified in the mixture are shown below. 

The formation of furfural is an acid-catalyzed dehydration reaction in which 3 moles of water are removed from 1 mole of hexose or pentose. The reactions are shown in Fig. 3.8. A common method for producing 5-(hydroxymethyl) furfural is the reaction of sucrose described by Haworth and Jones [8] in which a 30% solution of sucrose in water is heated to 120-140°C under pressure for 2-3 hr with 0.3% oxalic acid. In this process, the 5-(hydroxymethyl) furfural is formed primarily from the fructose part of sucrose and results in a 57% yield. 

Brown, D.W., Floyd, A.J., Kinsman, R.G., Roshan-Ah, Y., 1982. Dehydration reactions of fructose in nonaqueous media. Journal of Chemical Biotechnology 32, 920—924. 

The dehydration of fructose 40 or glucose into 5-hydroxymethylfurfural 41 is a process which has been exploited to convert biomass into higher value products. The reaction has been achieved using a chromium NHC complex, formed in situ from CrCl and the NHC 42 (Scheme 11.10) [16], The reaction is performed in the ionic liquid BMIM+Cl (l-butyl-3-methylimidazolium chloride). 

Heterogeneous catalysts, particularly zeolites, have been found suitable for performing transformations of biomass carbohydrates for the production of fine and specialty chemicals.123 From these catalytic routes, the hydrolysis of abundant biomass saccharides, such as cellulose or sucrose, is of particular interest. The latter disaccharide constitutes one of the main renewable raw materials employed for the production of biobased products, notably food additives and pharmaceuticals.124 Hydrolysis of sucrose leads to a 1 1 mixture of glucose and fructose, termed invert sugar and, depending on the reaction conditions, the subsequent formation of 5-hydroxymethylfurfural (HMF) as a by-product resulting from dehydration of fructose. HMF is a versatile intermediate used in industry, and can be derivatized to yield a number of polymerizable furanoid monomers. In particular, HMF has been used in the manufacture of special phenolic resins.125... 

Another, industrially relevant foUow-up reaction of isomaltulose comprises its ready conversion into 5-(a-D-glucosyloxymethyl)-furfural ( a-GMF ) by acidic dehydration of its fructose portion under conditions (acidic resin in DMSO, 120°C ) that retain the intersaccharidic linkage (Scheme 2.17). As this process can also be performed in a continuous-flow reactor,a most versatile building block is available from sucrose in two steps, of which the first is already industrially realized, and the second simple enough to be performed on a large scale. 

A prior report proposed that 3-deoxyhexosuloses participate in the formation of 11 (see Scheme 7). The 3-deoxyhexosuloses were isolated from heated, acid reaction mixtures involving D-fructose and L-sorbose. It was suggested that 3-deoxyhexos-2-ulose (39) underwent reversible equilibrium with 38, its cis form, and was further dehydrated at C-3 and C-4, to form 3,4-dideoxyhex-3-enos-2-ulose (40). This intermediate cy-clized to the furaldehyde. Experiments involving treatment of both... 

Thermolysis of D-fructose in acid solution provides 11 and 2-(2-hydrox-yacetyl)furan (44) as major products. Earlier work had established the presence of 44 in the product mixtures obtained after acid-catalyzed dehydrations of D-glucose and sucrose. Eleven other products were identified in the D-fructose reaction-mixture, including formic acid, acetic acid, 2-furaldehyde, levulinic acid, 2-acetyl-3-hydroxyfuran (isomaltol), and 4-hydroxy-2-(hydroxymethyl)-5-methyl-3(2//)-furanone (59). Acetic acid and formic acid can be formed by an acid-catalyzed decomposition of 2-acetyl-3-hydroxyfuran, whereas levulinic acid is a degradation prod-uct of 11. 2,3-Dihydro-3,5-dihydroxy-6-methyl-4//-pyran-4-one has also been isolated after acid treatment of D-fructose.The pyranone is a dehydration product of the pyranose form of l-deoxy-D-eo f o-2,3-hexodiulose. In aqueous acid seems to be the major reaction product of the pyranone. 

HMF has been discovered for the first time in 1895 by Diill and Kiermeyer who independently introduced a method of synthesis of HMF that they named oxy-methylfurfurol [65, 66]. Later, Haworth and Jones studied the mechanism of this reaction and showed that the formation of HMF involved a triple dehydration of hexoses [67]. Other studies performed by Van Dam, Kuster and Antal showed that the dehydration of hexoses (especially fructose and glucose) involved two possible pathways (Scheme 5) [63, 68, 69]. The path 1 involves the dehydration of ring systems (fructopyranose or glucopyranose), while the path 2 is based on acyclic derivatives (glucose and fructose open chain). 

Mixtures of organic solvent and water have also been studied (Scheme 11). hi this context, Watanabe and coworkers studied the catalytic dehydration of fructose to HMF at 150°C in acetone-water mixtures and in the presence of a cation-exchange resin catalyst (Dowex 50wx8-100) [92]. The use of acetone-water (70 30 w/w) as reaction medium resulted in a yield of HMF of 73% at 94% conversion. Moreover, under these conditions, the catalyst was stable for at least five catalytic runs. Assistance of microwave not only increased the selectivity to HMF but also had a beneficial effect on the reaction rate. In this context, Gaset et al. studied the activity of Lewatit SPC-108 (cation-exchange resin) in a mixture of organic solvent (MIBK or diethyl ketone or benzonitrile or butyronitrile or dichlor-oethylether or nitropropane) and water (from 1/7 to 1/12 by volume) at a temperature around 85-90°C Under these conditions, HMF has been obtained with a yield of 70-80% [93, 94]. 

Konig and co-workers also reported that Amberlyst 15 can promote the dehydration of carbohydrates to HMF using safe concentrated low melting mixtures consisting of choline chloride (ChCl) and about 50 wt% of carbohydrates. From fructose, glucose, sucrose, and inulin, HMF was produced with 40, 9, 27, and 54%, respectively within 1 h of reaction at a temperature around 100°C. Montmorillonite has also been used as a solid acid catalyst affording HMF with 49, 7, 35, and 7% yield from fructose, glucose, sucrose, and inulin, respectively [97]. 

Hydrolysis is the process by which a compound is broken down by reaction with water, thus it can be thought of as the opposite reaction of dehydration, where water is of course removed. Hydrolysis is a key reaction type in biomass chemistry, for it is central in the depolymerisation of polysaccharides to simpler monosaccharide building blocks, such as fructose, glucose, and xylose. 

Scheme 6 Fructose can be transformed into 5-hydroxymethyl furfural (HMF) via acid-catalyzed dehydration. Solid acid catalysts applied to facilitate the reaction are zeolites, ion-exchange resins and solid inorganic phosphates. With sporadic success, notably with inorganic phosphates, other carbohydrate sources such as inulin can also be transformed into HMF.

To accommodate these facts, the earliest mechanisms proposed for degradation of D-fructose assumed that it was present in the furanose form, and that the ring remained intact. It was assumed that the initial reaction was the elimination of water, to form the 1,2-enolic form of 2,5-anhydro-D-mannose, and that further dehydration resulted in 2-furaldehyde. The necessity for D-glucose to isomerize to D-fructose was assumed to account for the much lower reaction-rate of D-glucose. This mechanism does not account for the observation that 2,5-anhydro-D-mannose is less reactive than D-fructose, nor is there any evidence that 2,5-anhydro-D-mannose is present in reacting D-fructose solutions. Nevertheless, similar mechanisms have since been proposed.13-16 Because of the ease of mutarotation of D-fructose... 

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