Hydroxy acids Formaldehyde

P-Hydroxy acids lose water, especially in the presence of an acid catalyst, to give a,P-unsaturated acids, and frequendy P,y-unsaturated acids. P-Hydroxy acids do not form lactones readily because of the difficulty of four-membered ring formation. The simplest P-lactone, P-propiolactone, can be made from ketene and formaldehyde in the presence of methyl borate but not from P-hydroxypropionic acid. P-Propiolactone [57-57-8] is a usehil intermediate for organic synthesis but caution should be exercised when handling this lactone because it is a known carcinogen. 

Reaction of cyanohydrins with absolute ethanol in the presence of HCl yields the ethyl esters of a-hydroxy acids (3). A/-substituted amides can be synthesized by heating a cyanohydrin and an amine in water. Thus formaldehyde cyanohydrin and P-hydroxyethylamine lead to A/- (P-hydroxyethyl)hydroxyacetamide (4). 

RCH2OH + Co2(CO)7 (72) A known reaction of cobalt hydrocarbonyl suggests that the cobalt-carbon bond may be preferred. It has been reported that, under rather vigorous conditions, acetaldehyde or formaldehyde react with CO and a cobalt catalyst to give o -hydroxy acids or esters in alcohol solution (7). The intermediate with the carbon-cobalt bond probably is undergoing a CO insertion reaction, folllwed by a hydrolysis or... 

There are two new approaches to the 9-carboxylic acid 613, R = H. One consists in the reaction of dichlorocarbene with 4-methylacetophenone. The initially formed dichloroepoxide reacted with sodium hydroxide, and the main product from the reaction was the hydroxy acid 614, which underwent dehydration to 613 (R = H). The latter formed dimers in boiling water. Methyl (4-methylphenyl)acetate (615) reacted with formaldehyde, and the product 616 was dehydrated to 613 (R = Me). Hydrogenation over rhodium then gave the ester 617, which is also the product of hydroformylation of 615. " ... 

Calcium carbonate in suspension in glycerol and hydrogen peroxide causes a considerable structural alteration, with the appearance of formaldehyde, formic acid, glyceric acid, and hydroxymalonic acid. Under identical conditions, D-glucose gives formaldehyde, formic acid, acetic acid, oxalic acid, D-glucaric acid, and other, unidentified, hydroxy acids. ... 

Amino-hydroxy-acids are easily converted into oxazolidine-4- or -5-carboxylic acids or tetrahydro-oxazine-4-carboxylic acids, depending on structure, by reaction with formaldehyde. Scheme 108 illustrates the reaction for threonine the product is isolated as a benzoate. 

Not all polyoxyethylene association complexes form by one-to-one complexation. The polyoxyethylene/p-hydroxy-benzoic acid-formaldehyde copolymer complex in methanol has been reported to form by stepwise complexation (120,121). Uncertainty regarding the type of complexation may be due to changes in molecular weight distribution via partial fractionation that occurs during the complexation process (122). 

Under the influence of warm concentrated sulfuric acid a-hydroxy acids are cleaved to corresponding lower aldehydes or ketones and formic acid (CO + H2O). The aldehydes, or ketones, react with simultaneously added reagents, usually with some phenol (p. 213), as for example, 2,7-dihydroxynaphthalene or chromotropic acid in the case of formaldehyde, or guaiacol, carbazole, or p-hydroxydiphenyl in the case of acetaldehyde (115-117). 

Using a similar system, Johnson et al. have been able to effect the overall result of the Wittig reaction but using sulphur ylides. Thus, an alkylphenyl sulphoxide was converted into the sulphoximine with sodium azide, the imine group was methylated with formic acid-formaldehyde, and the N-methylimine was converted into the ylide (157) with n-butyl-lithium in THF. The ylide reacted with aldehydes or ketones by adding to the carbonyl group to produce the hydroxy sulphoximine (158). The sulphur group could... 

The reaction conditions can be varied so that only one of those monomers is formed. 1-Hydroxy-methylurea and l,3-bis(hydroxymethyl)urea condense in the presence of an acid catalyst to produce urea formaldehyde resins. A wide variety of resins can be obtained by careful selection of the pH, reaction temperature, reactant ratio, amino monomer, and degree of polymerization. If the reaction is carried far enough, an infusible polymer network is produced. 

Formaldehyde condenses with itself in an aldol-type reaction to yield lower hydroxy aldehydes, hydroxy ketones, and other hydroxy compounds the reaction is autocatalytic and is favored by alkaline conditions. Condensation with various compounds gives methylol (—CH2OH) and methylene (=CH2) derivatives. The former are usually produced under alkaline or neutral conditions, the latter under acidic conditions or in the vapor phase. In the presence of alkahes, aldehydes and ketones containing a-hydrogen atoms undergo aldol reactions with formaldehyde to form mono- and polymethylol derivatives. Acetaldehyde and 4 moles of formaldehyde give pentaerythritol (PE) ... 

Biacetyl is produced by the dehydrogenation of 2,3-butanediol with a copper catalyst (290,291). Prior to the availabiUty of 2,3-butanediol, biacetyl was prepared by the nitrosation of methyl ethyl ketone and the hydrolysis of the resultant oxime. Other commercial routes include passing vinylacetylene into a solution of mercuric sulfate in sulfuric acid and decomposing the insoluble product with dilute hydrochloric acid (292), by the reaction of acetal with formaldehyde (293), by the acid-cataly2ed condensation of 1-hydroxyacetone with formaldehyde (294), and by fermentation of lactic acid bacterium (295—297). Acetoin [513-86-0] (3-hydroxy-2-butanone) is also coproduced in lactic acid fermentation. 

The addition of P—H bonds across a carbonyl function leads to the formation of a-hydroxy-substituted phosphines. The reaction is acid-cataly2ed and appears to be quite general with complete reaction of each P—H bond if linear aUphatic aldehydes are used. Steric considerations may limit the product to primary or secondary phosphines. In the case of formaldehyde, the quaternary phosphonium salt [124-64-1] is obtained. 

Racemic pantolactone is prepared easily by reacting isobutyraldehyde (15) with formaldehyde ia the presence of a base to yield the iatermediate hydroxyaldehyde (16). Hydrogen cyanide addition affords the hydroxy cyanohydria (17). Acid-cataly2ed hydrolysis and cyclization of the cyanohydria (17) gives (R,3)-pantolactone (18) ia 90% yield (18). 

Pyrrole has been condensed under alkaline conditions with formaldehyde to give products of either N- or C-hydroxymethylation (Scheme 22). Although acid-catalyzed hydroxy-methylation is not a practical possibility, by addition of a reducing agent to the reaction mixture overall reductive alkylation can be achieved (Scheme 23). 

Ketones react with formaldehyde and perchloric acid to produce 2-isoxazolines and also with urea in a-methylnaphthalene at 200 °C (75MIP41600, 75ZOB2090, 79MI41612) with N-hydroxyurea they produce 3-hydroxy-2-carbamoylisoxazolidines or, after acid treatment, 2-isoxazolines are formed (Scheme 123) (75TL2337). 

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