Formose reaction addition

Fig. 7.—Rate of Formose Reaction (Addition Reactions Only) Showing Kinetics of Zero Order in Organic Compounds and First Order in Ca(OH)2 at 60° at Intermediate Levels of Conversion. [Rate of feed of HCHO (mole.liter" .min ) 0—, 0.94 —0.86 —, 0.78 (CHjOH stabilized) —A—, 0.35 —V—, 0.15.]...

Fig. 10.—Rate of Formose Reaction (Addition Reaction Only) versus Total Ca(OH)2 Present in System [Values of HCHO Feed Rate (mole.liter .min" ) and Temperature Noted] Showing Instabilities at Both Low and High Concentrations of Catalyst." Temperature —, 60° ----, 40° -----, 30°.

The formose reaction leads to the production of many sugars with the exception of ribose, which occurs in very low concentrations and it is hard to see how this could be increased. A variation on the formose reaction starting at the phospho-rylated glycoaldehyde intermediate, with the addition of base or in the presence of mineral substrate, produced a surprisingly large amount of ribose but this still... 

Additional advantages of the formamide condensation protocol were observed performing the reaction in the presence of catalysts which decompose formamide to formaldehyde. Formaldeyde is the most important pre-biotic precursor of sugars through a series of enolization and aldol-like condensation processes catalyzed under acidic or basic conditions, known as the formose reaction [100]. When formamide was heated at 160 °C in the presence of titanium dioxide (a catalyst able to degrade amides to aldehydes) [101] a complex mixture of nucleobase derivatives was obtained including adenine 1, purine 12, cytosine 17, N9-formylpurine 28, N9, N6-diformyladenine 29, 5-hydroxymethyluracil 30, thymine 31 and three novel... 

Butlerov found out that in alkaline medium (calcium hydroxide), formaldehyde HCHO polymerizes to form about 20 different sugars as racemic mixtures, Butlerov 1861. The reaction requires a divalent metal ion. Breslow found a detailed mechanism of reaction that explains the reaction products, (Breslow 1959). He found that glycol-aldehyde is the first product that is subsequently converted into glyceral-dehyde (a triose), di-hydroxy-acetone, and then into various other sugars, tetrose, pentose, and hexose. The formose reaction advances in an autocatalytic way in which the reaction product is itself the catalyst for that reaction with a long induction period. The intermediary steps proceed via aldol and retro-aldol condensations and, in addition, keto-enol tautomerizations. It remains unexplained how the phosphorylation of 3-glyceraldehyde leads to glycral-3-phosphate (Fig. 3.6). Future work should study whether or not ribozymes exist that can carry out this reaction in a stereo-specific way. 

When L-amino acids (with the exception of proline) catalyzed the formose reaction, an excess of D-glyceraldehyde formed. In contrast, without any special catalyst, an equal mixture of the d- and L-glyceraldehyde formed. The reaction conditions were prebiotic. Furthermore, addition of small amounts of water increased the enantiomeric excess to more than 90% (Breslow et al. 2010). An intriguing mechanism of chiral induction takes place when chiral L-amino acids (such as the ones found in the Murchison meteorite) were used as basic catalysts in the formose reaction induced about 10% ee of D-threose (Pizzarello and Weber 2004). Stereo-selective syntheses of pentose sugars occur under realistic prebiotic conditions when LL-dipeptides catalyzed the formose reaction (Pizzarello and Weber 2010). 

Formose is a general term applied to the mixture of monosaccharides formed by self-addition of formaldehyde in aqueous alkaline solution. The present article briefly describes the history of research on formose, and discusses the formose reaction and the nature of the formose sugars. 

The formose reaction in detail, however, consists of a series of reactions primary self-addition of formaldehyde followed by aldol reaction of products with each odier and with formaldehyde. Cannizzaro and cross-Cannizzaro reactions occur, as well as Lobry de Bruyn-Alberda van Ekenstein rearrangements. Product decomposition (for example, to chromophores) occurs if the reaction conditions are unduly severe. The monosaccharides formed are all dl (racemic), with no optical rotatory... 

The conversion of formaldehyde by the Cannizzaro reaction into formic acid and methanol lessens the yield of formose sugars. Addition of... 

The Cannizzaro reaction of formaldehyde is far from a simple kinetic process that could be characterized by first- or second-order kinetics, and that would be a single reaction in which methanol and formate are produced. Rather, it proceeds in alkaline medium in conjunction with the formose reaction, the autocatalytic self-addition of formaldehyde to produce glycolaldehyde, which is then followed by aldol reaction to afford higher aldoses and ketoses. Mono-, di-, tri-, and tetra-valent bases, as well as nitrogenous bases, have been reported to catalyze both reactions homo-... 

The formose reaction continues to attract attention. Detailed product analysis has been carried out on the autocatalytic condensation of formaldehyde using capillary g.l.c.-mass spectrometry. In addition to the previously reported sugars, pent-2-uloses, hex-3-uloses, DL-apiose and other branched hexoses were found. 

In 1961 and 1965, a stepwise-addition model was presented by Pfeil and coworkers for the formation of the sugar molecules in formose. The first addition product of formaldehyde was glycolaldehyde (C2) which, in the next step, underwent further reaction with formaldehyde to afford two C3 products, namely, glyceraldehyde and l,3-dihydroxy-2-propanone. The repetition of such reactions, coupled with keto-enol tautomerization and epimerization, was presumed to lead to the formation of C4, Cb, and Ce aldoses and ketoses, and even to C and Ca ketoses to some extent. 

In 1952, Pfeil and Schroth reported that, in formose formation, the Cannizzaro reaction takes part, simultaneously and competitively, with the addition reaction. Whereas alcohols of low molecular weight, 1,4-dioxane, tetrahydrofuran, and other compounds repress the Cannizzaro reaction, the hydroxides of alkaline-earth and alkali metals activate the reaction, with only one exception, namely, thallium hydroxide, which catalyzes the addition reaction specifically. In 1971, the two reactions, namely, the addition reaction and the Cannizzaro reaction, were quantitatively and differentially measured by Fujino. When measured for the... 

The main reactions for formose-sugar formation are the primary addition and then a secondary, crossed-aldol reaction. The former is the... 

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