Formaldehyde formose reaction

The formation of sugars from the reaction of formaldehyde under alkaline conditions was discovered in 1861 and is known as the formose reaction , although it is not understood fully (Figure 8.7). It requires the presence of suitable inorganic catalysts such as Ca(OH)2 or CaCOr, either of which may be found on a prebiotic Earth. The reaction is autocatalytic and produces over 40 different types of sugars, some rings, some long chains. 

Are there other types of self-replication in nature, possibly based on a quite different mechanism There are not many, but there is a famous case the formose reaction, described in 1861, and based on a reaction cycle of formaldehyde. This reaction has already been mentioned in Chapter 3, on the subject of prebiotic... 

Figure 7.4 Schemae of the formose reaction (a) spontaneous, slow formation of glycolaldehyde from formaldehyde (b) after one cycle, one new molecule of glycolaldehyde is produced. The structural isomers of sugars are specified by the carbon skeleton and by the position of the carbonyl group (open circle). (Adapted, with some modifications, from Maynard Smith and SzathmSry, 1995.)...

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... 

One experimental approach would be to generate heterogeneous vesicles in broths containing the constituents of the formose reaction, initially limiting the concentration of formaldehyde. After leaving the system for a while, formaldehyde would be added to the solution. Those vesicles that grew and divided fastest would be selected for. There may be rare conditions under which the constituents of the formose reaction are permeable to the membrane. They enter the vesicle and become trapped as soon as those conditions change. Formaldehyde could then enter the vesicles and allow the autocatalytic cycle to run. 

Under UV irradiation, aqueous solutions of formaldehyde and ammonium salts produce imidazoles (Scheme 85). It is conceivable that the irradiation has catalyzed a formose reaction, yielding trioses and glycolaldehyde, and that reaction of these species with ammonia could account for the products isolated. Such a reaction might be classed as a primitive-life synthesis, as might the observation that hydrogen cyanide and liquid ammonia react to form 4,5-dicyanoimidazole and adenine (70AHC(12)103). 

In the presence of formaldehyde (0.5 mol equiv.), sugar phosphates were formed in up to 45% yield, with pentose-2,4-diphosphates dominating over hexose triphosphates by a ratio of 3 1 (Scheme 13.2, Route B). The major component was found to be D,L-ribose-2,4-diphosphate with the ratios of ribose-, arabinose-, lyxose-, and xylose-2,4-diphosphates being 52 14 23 11, respectively. The aldomerization of 2 in the presence of H2CO is a variant of the formose reaction. It avoids the formation of complex product mixtures as a consequence of the fact that aldoses, which are phosphorylated at the C(2) position, cannot undergo aldose-ketose tautomerization. The preference for ribose-2,4-diphosphate 5 and allose-2,4,6-triphosphate formation might be relevant to a discussion of the origin of ribonucleic acids. 

There is a debate over whether the classical formose reaction [3-5] might have played a role in the prebiotic synthesis of carbohydrates. When a slurry of carbonate-apatite is boiled with 0.5 M formaldehyde at pH 8.5 a yield lower then 40% in sugars is reached after a few hours. 

The classical formose reaction gives a very large number of carbohydrates including branched-chain isomers [17,18,19]. Straight-chain carbohydrates such as trioses, tetroses, pentoses, and hexoses are readily obtained in good yield by a reaction of formaldehyde with syngas in the presence of RhCl(CO)(PPh3)2 and tertiary amines [37]. 

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. 

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 is principally an aldol reaction (anionic mechanism) of formaldehyde in an aqueous solution. By a complex repetition of the reaction, the carbon chain grows, to yield a variety of monosaccharides from C2 to Cs. 

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... 

Pfeil and coworkers presented a model for the synthetic pathway of formose, shown in Scheme 5. A similar, but more detailed, model was given by Mizuno and coworkers, who investigated the intermediates in the reaction by chromatographic fractionation of alditol acetate derivatives by g.l.c. (see Table IV). Weiss and coworkers conceptualized the formose reaction as a consecutive-parallel scheme (see Scheme 6) proceeding to the C level, and reported a series of experiments in the continuously stirred tank-reactor previously mentioned to determine the effect of various concentrations of formaldehyde and calcium hydroxide on the reaction rate. The advantage of the tank reactor is that conversions in the autocatalytic system can be controlled, and reaction rates can be measured directly. When the formaldehyde feed-rate was kept constant, and the feed rate for calcium hydroxide varied, products were obtained... 

Scheme 6.—Approximation of the Formose Reaction as a Network of Simultaneous and Consecutive Reactions. [A is species of carbon number n. Formaldehyde path shown by heavy arrows. " ]...

In order to eliminate Cannizzaro effects from the data for the formaldehyde reaction-rate, the formose reaction-rate, Tf was defined [total... 

Figure 7 shows the formose reaction-rate as a function of molarity of calcium hydroxide in the product. One line, independent of the concentration of formaldehyde in the reactor, fits data at intermediate conversion-levels this line passes through the origin. In a study of the selfaddition of formaldehyde catalyzed by magnesium oxide, Schmalfusz and Kalle observed similar behavior, almost independent of concentrations of formaldehyde and first-order in magnesium oxide that had not been consumed in the Cannizzaro reaction. A zero-order rate-constant... 

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