Hydroxy aldehydes from formaldehyde

The old Maquenne synthesis of imidazoles [64] is seldom used nowadays. It was originally used to make imidazole-4,5-dicarboxylic acids from tartaric acid dinitrate and either an aliphatic aldehyde or formaldehyde precursor in the presence of ammonium ions at pH 3.5-6.5. The procedure is not an entirely pleasant experience, and has been happily superseded by other approaches, but it may be useful on occasion to make compounds such as vinyl-, hydroxy-and methoxy-substituted 2-arylimidazole-4,5-dicarboxylic acids [65]. Use of dialkyltartrate dinitrates gives the corresponding imidazole-4,5-dicarboxylates in 45-65% yields [31]. 

Formaldehyde dimethyl dithioacetal 5-oxide (FAMSO 113) and its ethyl analog are widely used as synthetic carbonyl equivalents. - Addition of the lithio derivative of (113) to aldehydes and ketones followed by acidic hydrolysis is a preparative method for a-hydroxy aldehyde derivatives (equation 27). A chiral analog of (113), (5)-formaldehyde di-p-tolyl dithioacetal 5-oxide (114), can be synthesized from (-)-mentyl (/ )-p-toluenesulfinate. °° The reaction of the lithio derivative of (5)-(114)... 

Like hydration, these addition reactions are governed by equilibria that usually favor the starting carbonyl compound. Hemiacetals, like hydrates, are therefore usually not isolable. Exceptions are those formed from reactive carbonyl compounds such as formaldehyde or 2,2,2-trichloroacetaldehyde. Hemiacetals are also isolable from hydroxy aldehydes and ketones when cyclization leads to the formation of relatively strain-free five- and six-membered rings. 

This reaction is based on the formation of a color in a mixture of an aqueous sodium nitroprusside solution with carbonyl compounds in an alkaline medium. A positive test is obtained with aliphatic and certain aromatic aldehydes and aromatic and aliphatic ketones. The literature data on this reaction are conflicting and no general rule can be expressed about which carbonyl compounds give the reaction and which do not. For example, the color is not produced with formaldehyde, glyoxal, benzaldehyde, o-hydroxy-benzaldehyde, chloral, vanillin, benzophenone, naphthyl phenyl ketone, trihydroxybenzophenone, benzil, acetophenones substituted on the aromatic nucleus with hydroxyl, etc. The reaction can therefore be used for the differentiation of certain types of aldehydes and ketones, as, for example, acetaldehyde from formaldehyde, and acetophenone from benzophenone or hydroxyacetophenone, etc. Further, various colors formed in alkaline media or after the subsequent acidification of the reaction mixture can also be used for differentiation. Sodium hydroxide can be replaced by ammonia, piperidine... 

Henry reactions have been extensively exploited for the synthesis of nitrate ester explosives. The condensation of nitroalkanes with aldehydes, followed by esterification of the hydroxy groups with nitric acid, leads to a number of nitrate ester explosives (see Chapter 3). The two examples given above (166 and 167) are synthesized from the C-nitration of the polyols obtained from the condensation of formaldehyde with nitromethane and nitroethane respectively. 

Hydroxy-l-nitrohydrazones (809) react with primary amines and formaldehyde to give 2,3,4,5-tetrahydro-l,2,4-triazines (810) (64MI21901), and similar compounds (812) can be obtained from the reaction of aldehyde hydrazones (811) with primary amines and aldehydes (74KGS425, 75KGS1290, 74UKZ1220). 

Many other compounds have been identified as products of the sugar-amino acid reaction. Amongst these are 2,3-butanedione,195 formaldehyde,196 pyruvaldehyde,20,195, 247, 248 3-hydroxy-2-butanone,248 hydroxy-2-propanone,248 and acetaldehyde.73 Imidazoles,196, 249-251 especially 4(5)-methylimidazole, have also been isolated from the reaction under mild conditions, and could have been formed from a-hydroxy ketones or aldehydes plus amino compounds. Following the early identification247 of pyru-valdehyde as a product of the Maillard reaction, much work was done in an attempt to show that this reactive compound plays a major role in the reaction,249 262 254 but, that this is so is by no means certain.7... 

The furanic aldehydes 5-(hydroxy-methyl)furfural and 2-furaldehyde, systematically present in the toasted wood, can be formed by the thermal degradation of 3-deoxyosone during sugar pyrolysis or Maillard reactions (27). They could also be formed from glyceraldehyde, coming from degradation of DDMP, by condensation with subsequent elimination of water or formaldehyde (24). 

Among hydroxybenzaldehydes, the o- and p- hydroxy isomers are the most important for commercial applications in agricultural, flavor and fragance, pharmaceutical or polymer fields (ref. 1). The two main processes for the manufacture of hydroxybenzaldehydes are both based on phenol. The most widely used process is the saligenin process. Hydroxybenzyl alcohols (o- and p- isomers) are produced from base - catalyzed reaction of formaldehyde with phenol (ref. 2). Air oxidation of these alcohols over a suitable catalyst (based on palladium or preferentially on platinum) produces hydroxybenzaldehydes (ref. 3). The Reimer -Tiemann process allows the coproduction of o- and p- hydroxybenzaldehydes (ref. 4). Treatment of phenol with aqueous chloroform and sodium hydroxide leads to benzal chlorides which are rapidly hydrolyzed by alkaline medium to aldehydes. The previous processes need two chemical steps and produce salt effluents. 

Early examples, due to Grewe, dealt with the formation of hydroisoquinolines from the reaction of aldehydes with cyclohexenylethylamine and its derivatives. The cis stereochemistry of the 10-hydroxy-decahydroisoquinoline (M) produced from treatment of (59) with formaldehyde and formic acid demonstrates that the alkene participant undergoes trans addition. ... 

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