Aldehydes hydroxymethylation

Under acidic conditions, furfuryl alcohol polymerizes to black polymers, which eventually become crosslinked and insoluble in the reaction medium. The reaction can be very violent and extreme care must be taken when furfuryl alcohol is mixed with any strong Lewis acid or Brn nstad acid. Copolymer resins are formed with phenoHc compounds, formaldehyde and/or other aldehydes. In dilute aqueous acid, the predominant reaction is a ring opening hydrolysis to form levulinic acid [123-76-2] (52). In acidic alcohoHc media, levulinic esters are formed. The mechanism for this unusual reaction in which the hydroxymethyl group of furfuryl alcohol is converted to the terminal methyl group of levulinic acid has recendy been elucidated (53). 

Aldehydes form addition products with sulfamic acid salts. These are stable ia neutral or slightly alkaline solutions but are hydroly2ed ia acid and strongly alkaline solutions. With formaldehyde, the calcium salt of the methylol (hydroxymethyl) derivative [82770-57-8], Ca(02SNHCH20H)2, is obtained as a crystalline soHd. 

The phenomenon of 5-hydroxymethylation is a standard case of electrophilic attack. Thus uracil (83 R = H) and paraformaldehyde in aqueous alkali furnish 5-hydroj(ymethyl-pyrimidine-2,4(l//,3//)-dione (83 R = CH20H) in good yield (59JA2521). Aromatic aldehydes react differentiy to yield 5-benzylidene derivatives of, for example, 1-methylbar-bituric acid (78CC764). 

Pyrazolones show a great variety of reactions with carbonyl compounds (B-76MI40402). For instance, antipyrine is 4-hydroxymethylated by formaldehyde and it also undergoes the Mannich reaction. Tautomerizable 2-pyrazolin-5-ones react with aldehydes to yield compound (324) and with acetone to form 4-isopropylidene derivatives or dimers (Scheme 8 Section 4.02.1.4.10). 

In general, the reaction between a phenol and an aldehyde is classified as an electrophilic aromatic substitution, though some researchers have classed it as a nucleophilic substitution (Sn2) on aldehyde [84]. These mechanisms are probably indistinguishable on the basis of kinetics, though the charge-dispersed sp carbon structure of phenate does not fit our normal concept of a good nucleophile. In phenol-formaldehyde resins, the observed hydroxymethylation kinetics are second-order, first-order in phenol and first-order in formaldehyde. 

The second phase in resole formation is reaction of the activated phenol with the aldehyde to form the phenol alcohol derivative. When the aldehyde is formaldehyde, the derivative is a hydroxymethyl phenol and the process is known as methylolation. Scheme 2 illustrates this reaction. Since resoles are usually made with excess aldehyde, more than one substitution may be made on the ring. When the reactants are phenol and formaldehyde, up to three methylol groups may be substituted. This reaction has been extensively studied and the rates of... 

The methyl group m 3-methyl-4,5,6,7-tetrafluoroindoles is oxidized to an aldehydic or a hydroxymethyl group with high selectivity by selenium dioxide [90] (equation 83)... 

Aliphatic and aromatic aldehydes condensed with 2-amino-(62BRP898414), 5-amino- (80AJC1147), or 8-amino-l,2,4-triazolo[l,5-cjpyrimidines (68JOC530) to give the related Schiff bases. Treatment of the 2-amino-5-methyl-l,2,4-triazolo[l,5-c]quinazoline 11 with formaldehyde and piperidine in the presence of acetic acid gave the 2-hydroxymethyl-amino-5-(2-piperidinoethyl) derivative 172. Utilization of aromatic aldehydes and piperidine in this reaction gave the 2-arylideneamino-5-styryl derivatives 173 (68CB2106) (Scheme 67). 

Further, isoxazole derivatives were subjected to two related reactions. 3,5-Dimethylisoxazole was found to react in the presence of dry hydrogen chloride with aromatic aldehydes (chlorobenzylation, 72- 71),and with formaldehyde in the presence of sulfuric acid it undergoes hydroxymethylation (72- 73). ... 

A subclass of lyases, involved in amino acid metabolism, utilizes pyridoxal 5-phosphate (PLP, 3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinecarbaldehyde) as a cofactor for imine/ enamine-type activation. These enzymes are not only an alternative to standard fermentation technology, but also offer a potential entry to nonnatural amino acids. Serine hydroxymethyl-tansferase (SHMT EC 2.1.2.1.) combines glycine as the donor with (tetrahydrofolate activated) formaldehyde to L-serine in an economic yield40, but will also accept a range of other aldehydes to provide /i-hydroxy-a-amino acids with a high degree of both absolute and relative stereochemical control in favor of the L-erythro isomers41. 

Metriol (Pentaglycerol, 2-(Hydroxymethyl)-2-me thy 1-1,3 -p rop ane diol, Methyltrime thylol-methane). H3C.C(CH2OH)3 mw 120.15 white needles from abs ale mp 199° (sublimes without decompn). Was first prepd by Hosaeus (Ref 2) by condensing formaldehyde and propionic aldehyde in cold aq soln in the presence of lime. Metriol is v sol in w, ale and acet ac is insol in eth. It may be nitrated to an expl trinitrate, and acetylated to a nonexpl triacetate Refs 1) Beil 1, 520 2) H. Hosaeus, Ann... 

Symmetrical 1,4-diketones (249) can be prepared by the reaction of phenyl vinyl sulfones (53) or divinyl sulfone with aldehydes in the presence of 3-benzyl-5-(2-hydroxymethyl)-4-methylthiazolium chloride as a catalyst (equations 148 and 149)142. 

Besitzen Aldehyd und Keton a-H-Atome, so werden diese zunachst durch Hydroxy-methyl-Gruppen ersetzt. Auf diese Weise erhalt man z. B. aus Acetaldehyd und vier Molen Formaldehyd Pentaerythrit (73% d.Th.)4 bzw. aus Cyclohexanon mit fiinf Molen Formaldehyd 2-Hydroxy-1,1,3,3-tetrakis-[hydroxymethyl]-cyclohexan (73-85% d.Th.). Da es sich hierbei zunachst um eine Aufbaureaktion handelt, wird diese Umsetzung in Bd. VI/la/2, S. 1314f. geschlossen abgehandelt (vgl. auch Lit.s). 

The biotransformation of gylcerol trinitrate by strains of Bacillus thuringiensis/cereus or Enterobacter agglomerans (Meng et al. 1995), by strains of Pseudomonas sp., and some Entero-bacteriaceae (Blehert et al. 1997) involves the expected successive loss of nitrite with the formation of glycerol. The biotransformation of pentaerythritol tetranitrate by Enterobacter cloacae proceeds comparably with metabolism of two hydroxymethyl groups produced by loss of nitrite to the aldehyde (Binks et al. 1996). 

The kinetics of deuterium isotope exchange between diphenyl phosphine and t-butylthiol have been studied by H n.m.r. spectroscopy.274 A negative temperature coefficient was observed for the reaction of a perf1uoroalky1 phosphite with a fluorinated aldehyde.275 The kinetics for the reaction of alcohols with phosphoryl trichloride bore strong similarities to those of carboxylic acid derivatives.276 An interesting report desribed the solvolysis of ary 1 hydroxymethyl-phosphonates. It was shown that a phosphoryl group does not prevent carbocation formation on an immediately adjacent carbon atom.277... 

Polar polyoxyethylene-polyoxypropylene (POEPOP) resin, deriva-tized with a 4-hydroxymethyl phenoxy linker, was used as a solid support for lanthanide triflate-catalyzed Mukaiyama-type solid-phase aldol reactions.282 The use of an aqueous solvent was found to be crucial. The reactions on an N-terminal peptide aldehyde substrate proceeded in very high yields. 

Hydroxymethylation (formaldehyde) of nitro-imidazole 76 affords 77, which is oxidized to aldehyde 78. To prepare the other fragment for this convergent synthesis, reaction of epichlorohydrin with morpholine leads to the aminoepoxide 79, which is reacted with hydrazine to afford 80. Reaction of this substituted hydrazine with dimethyl carbonate affords oxazolinone 81 by sequential ester interchange reactions. Condensation of 81 with aldehyde 78 affords the antitricho-... 

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