Formose reaction induction period

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. 

A remarkably selective conversion of formaldehyde into glucose was reported by Weiss and co-workers.The reaction, carried out at 98°, was initiated by adding aqueous sodium hydroxide to a calcium chloride-formaldehyde solution. Under these conditions the induction period was IS seconds, and at 18% formaldehyde conversion level hexoses were formed with 84.3% selectivity. Analysis by glc of the products [in the form of trimethyl silyl (TMS) derivatives] revealed that no branched sugars were formed and glucose constituted about 90% of the reaction mixture. It should be noted that analysis—gas chromatography-mass spectrometry (gc-ms) of the corresponding alditol acetates—of the mixtures obtained in the formose reaction carried out under normal conditions revealed the presence of 33-37 components. ... 

A mixture of 2-C-hydroxymethylglycerol, 2,4-bis-C-hydroxymethylpentitol, and 3-C-hydroxymethylpentitol has been isolated from a calcium hydroxide-catalysed formose reaction from which most of the calcium ions were removed as sparingly soluble salts or chelates at the end of the induction period/... 

A set of modified conditions has allowed some control over the complex formose reaction so that the branched-chain alditols (6)—(8) represented the major products formed initial catalysis was effected with calcium hydroxide, which was removed at the end of the induction period with oxalate, and the reaction was then adjusted to pH 12 with potassium hydroxide. ... 

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