2-Furaldehyde formation, mechanism

Kinetic evidence from the DL-glycerose-1,3-dihydroxy-2-propanone isomerization has indicated that aldose-ketose isomerization and formation of a 3-deoxyosone proceed through a common intermediate. Ashmarin and coworkers and Petuely s observations, which indicate general acid and base catalysis of 2-furaldehyde formation, tend to support such a mechanism, since 2-furaldehyde and its derivatives may indeed be formed from 3-deoxyosones. 

The resinification of 2-furaldehyde promoted by acidic substances or by heat has been known to chemists since the end of last century, and attempts to explain the mechanism leading to the formation of black, insoluble resins have been published... 

The reaction mechanism postulated by Wolfrom, Schuetz and Cavalieri87 for the formation of 5-(hydroxymethyl)-2-furaldehyde from D-glucose involves the enol (XXXV) of 3-deoxy-D-glucosone as an intermediate an alternative pathway proposed by these same workers included the enol... 

Neher and Lewis177 obtained 2-furaldehyde from 2,3,4-tri-O-methyl-L-arabinose by heating with dilute acid after preliminary enolization with alkali. Isbell83 proposed a mechanism for this conversion similar to that for the conversion of tetra-0-methyl-(2-hydroxy-D-glucal) into 5-(hydroxymethyl)-2-furaldehyde XLIV was suggested as an intermediate. In Hurd and Isenhour s178 scheme for the formation of 2-furaldehyde from free pentose, the enol (XLV) of a 3-deoxypentosone was regarded as an inter-... 

The mechanism of pentose dehydration has been a matter of study for several years. The accepted pathway (see Scheme 1) to 2-furaldehyde from a pentose, in this case D-xylose (1), involves the reversible formation of a 1,2-enediol (2) followed by dehydration to the enolic form (3) of a 3-deoxypentosulose, which is further dehydrated to the 3,4-dideoxypent-3-enos-2-ulose (4) prior to cyclization to afford 2-furaldehyde 5. This mechanism, initially suggested by Isbell,has been substantiated by later work. This confirmation required incorporation of deuterium or tri-tium into the furaldehyde at various ring positions. However, when... 

Decarboxylation of L-ascorbic acid in acid solutions has been proposed to involve one of two possible mechanisms. One pathway required dehydration, decarboxylation, and formation of 2-furaldehyde. The second pathway involved a rearrangement to the 3-keto form followed by a... 

General aspects of the mechanisms of sugar dehydration have been discussed in Section II, and by Anet8 in an earlier Volume of this Series. Anet s scheme for formation of 2-furaldehyde, shown in the following scheme, was based on experimental evidence then avail-... 

The formation of such chromones as 3,8-dihydroxy-2-methyl-chromone by treating uronic acids or pentoses with dilute acid was reported by Aso,119 and studied by Popoff and Theander,120 who obtained a number of these compounds in 3.5% yield, as well as some catechols. Although nothing is yet known about the mechanism of formation of these compounds, the fact that the chromones contain 10 carbon atoms and are produced both from pentoses and uronic acids suggests that they may be derived from 2-furaldehyde or re-ductic acid, or produced from a decarboxylated intermediate. 

Aso98 first proposed 5-hydroxy-2-oxo-3-pentenal (94) as an intermediate in the conversion of uronic acids to reductic acid,190 191 but this proposal does not appear to have been experimentally tested, although the intermediate was prepared.190 Isbell121 suggested a mechanism in which the formation of reductic acid and 2-furaldehyde from pentoses and uronic acids results from the reaction of different tautomers of 94. Although other mechanisms have been suggested,100 102 115 Isbell s original scheme seems adequate to explain the experimental facts. 

Obviously, a similar mechanism can be presented for the formation of carbocyclic compounds from the hexoses, but less is known about the products and the variation in their distribution within the group. Most of the work with the hexoses has been conducted with D-glucose and D-fructose. It is known that D-mannose and D-galactose give significantly lower yields of 5-(hydroxymethyl)-2-furaldehyde than either D-glucose or D-fructose when treated in concentrated sulfuric acid,52 but no homolog of 75 has been reported. 

The mechanism of acid-catalyzed decarboxylation of hexuronic acids has been the subject of many investigations.231,232 The formation of carbon dioxide is accompanied by the formation of 2-furaldehyde, C5H402 (82) as the main product, along with considerable amounts of humins however, both 5-formyl-2-furoic acid (83) and reductic acid (84) have been isolated as end products from treatment of hexuronic acids with strong acid. 

The 2-hydroxyglycals provide additional source material for the study of dismutation reactions, the reaction of the acyl derivatives of the hexoses climaxing in di-O-acetylkojic acid or di-O-benzoylkojic acid through loss of acetic or benzoic acid and of the O-methyl derivatives in 5-(methoxymethyl)-2-furaldehyde through loss of methanol. The formation of the 2-hydroxyglycals as intermediates in the reaction of some alkalis on sugars has been proposed by Kusin8 in an effort to explain the cationic dependence exhibited by the products. His mechanism has not, however, been established. 

Antal, M. J., Leesomboon, T., Mok, W. S., and Richards, G. N., Kinetic-studies of the reactions of ketoses and aldoses in water at high-temperature. 3. Mechanism of formation of 2-furaldehyde from D-xylose. Carbohydrate Res 1991, 217,71-85. 

Two pyrolysis products that are formed during pectin pyrolysis are furfural (2-furancarboxaldehyde, 2-furaldehyde) and 4-(hydroxymethyl)-1,4-butyrolactone. The proportion of the butyrolactone compared to that of furaldehyde in the pyrolysis products of pectin was found to correlate with the methylation degree of pectin [6]. The formation of 2-furaldehyde from the galacturonic unit probably takes place with the following mechanism (hydrogens are shown with shorter bonds) ... 

The formation of deoxyosones, such as, for example, the 3-deoxyosones, appears to be the most important of the dehydration reactions which may take place during Lobry de Bruyn-Alberda van Ekenstein transformations. This type of reaction, which NeP first proposed in suggesting mechanisms for saccharinic acid formation, is difficult to study because the products are seldom stable in the reaction mixtures in which they are formed. Nevertheless, several different lines of evidence now indicate that reducing sugars undergo primary dehydrations of this kind, and that deoxyosones do indeed mediate in saccharinic acid formation in basic solutions, as well as in production of 2-furaldehyde and its derivatives in acidic media. 

Furaldehyde and reductic acid are formed by acidic treatment of hexuronic acids. Under special conditions, reductic acid is obtained as the major product. These reactions have been studied by Stutz and Deuel, who discussed a mechanism for the formation of the two compounds that involved splitting between C-5 and C-6 by decarboxylation. There is, at present, insufficient evidence to permit formulation of any mechanism for the degradation of the keto-n-glucosides. However, it is the writer s opinion that a ring closure between C-6 and C-2 in the common enediol derived from either the 2-keto or 3-keto compounds is po ible. In a pre-... 

A wide range of carbohydrates is degraded by acids to furan compounds. For example, pentoses give 2-furaldehyde, and hexoses, 5-(hydroxymethyl)-2-furaldehyde (58), which may react further to yield levulinic acid. In 1910, Nef suggested the first mechanism, (55) to (58), for the formation of 5-(hydroxymethyl)-2-furaldehyde. His proposal was made at the end of his classical paper on the saccharinic acids, and was overlooked by subsequent workers and reviewers. In 1944, Haworth and Jones advanced an identical mechanism for the formation of 5-(hydroxymethyl)-2-furaldehyde from D-fructose. 

Nef assumed that, since n-glucose and o-mannose give smaller yields of 5-(hydroxymethyl)-2-furaldehyde than does D-fructose, aldoses are first enolized and then converted into ketoses. He then proposed that D-fructose reacts in the furanose form (55) to give (56), the enol form of chitose (2,5-anhydro-D-mannose). His mechanism is based on the formation of 5-(hydroxymethyl)-2-furaldehyde from chitose. 

Nef s mechanism was recently modified by Mednick and by Moye and Krzeminski. Instead of the formation of (57) from (56), they proposed, in effect, a /3-hydroxy-carbonyl elimination to yield the a, 8-unsaturated aldehyde (59). Although, with this alteration, the steps from (56) to (59) and to 5-(hydroxymethyl)-2-furaldehyde are quite plausible, no evidence has been presented for the formation of (56), nor have any of the above... 

The other mechanisms for the formation of 5-(hydroxymethyl)-2-furaldehyde involve the aldehyde form of aldoses or the keto form of ketoses, in contrast to Nef s mechanism, which required the furanose form of a ketose. Hurd and Isenhour, Isbell, and Wolfrom and coworkers all based their suggestions on the well-known elimination of a hydroxyl group in a position /3 to a carbonyl group. They applied their mechanisms to aldoses only. However, Isbell proposed that the /3-elimination proceeds by a consecutive electron-displacement involving an enediol intermediate (63), the enolic form of the aldose (62). Later, Wolfrom and coworkers also proposed the enediol as a possible intermediate. 

Isbell, and also Wolfrom and coworkers, favored 3,4-dideoxypentosulos-3-enes (66) as intermediates. The only experimental evidence which had been obtained at this stage was the isolation of the hexosulos-3-ene (32) in the formation of 5-(methox5Tnethyl)-2-furaldehyde (see Section IV,2 p. 193). The isolation of more intermediates has complicated the mechanism, which will now be dealt with in more detail. 

Table II presents the quantitative results of those components volatile enough for GC analysis. At low pH the furan compounds predominate when both glucose and xylose are exposed to 300 C. This is not unexpected since all pentoses form 2-furaldehyde(2) in high yield when exposed to aqueous acid solution( ). However, the presence of 2 in the glucose reaction mixture is of interest. The major product obtained from hexoses at elevated temperatures and aqueous acid is 5-hydroxymethyl-2-furaldehyde(1) with minor amounts of 2-(hydroxyacetyl)furan(15). The 2-furaldehyde has been detected after acidic treatment of fructose(1 ), glucose(15,17), and is a major component after the thermolysis of cellulose in distilled water( ). One plausible explanation for the formation of 2 may involve loss of formaldehyde(18) from glucose with consequent pentose formation. It should be noted that the pyrolysis of 1 does produce a small amount of 2( ). However, the reaction conditions are sufficiently different to suggest a different mechanism for hydrothermolysis.

The formation of 2-furaldehyde on acid-catalysed dehydration, etc., of 1-benzyl-amino-l-deoxy-D-f/ireo-pentulose and l-benzylamino-l-deoxy-o-fructuronic acid has been studied in isotopically labelled water (either acidified deuterium oxide or tritiated water).The pattern of labelling of the 2-furaldehyde derived from the latter compound is consistent with a mechanism involving the decarboxylation of a Py-unsaturated carboxylic acid intermediate (see also p. 136). 

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