Formaldehyde aldol reactions

Pentaerythritol is produced by reaction of formaldehyde [50-00-0] and acetaldehyde [75-07-0] in the presence of a basic catalyst, generally an alkah or alkaline-earth hydroxide. Reaction proceeds by aldol addition to the carbon adjacent to the hydroxyl on the acetaldehyde. The pentaerythrose [3818-32-4] so produced is converted to pentaerythritol by a crossed Cannizzaro reaction using formaldehyde. All reaction steps are reversible except the last, which allows completion of the reaction and high yield industrial production. 

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) ... 

Neopentyl glycol (2,2-dimethyl-1-propanol [126-30-7]) another important iadustrial derivative of isobutyraldehyde, is obtained from the aldol reaction product of isobutyraldehyde with formaldehyde followed by hydrogenation. 

The dimer of 1-methyl- -pyrroline (39) was obtained by reduction of N-methylpyrrole with zinc and hydrochloric acid (132) and, together with the trimer, by mercuric acetate dehydrogenation of N-methylpyrrolidine (131). J -Pyrroline-N-oxides form dimers in a similar manner (302). Treatment of 1,2-dimethyl-zl -piperideine with formaldehyde, producing l-methyl-3-acetylpiperidine (603), serves as an example of a mixed aldol reaction (Scheme 18). 

I If one of the carbonyl partners contains no or hydrogens, and thus can t form an enolate ion to become a donor, but does contain an unhindered carbonyl group and so is a good acceptor of nucleophiles, then a mixed aldol reaction is likely to be successful. This is the case, for instance, when either benz-aldehyde or formaldehyde is used as one of the carbonyl partners. 

The aldol reaction is a carbonyl condensation that occurs between two aldehyde or ketone molecules. Aldol reactions are reversible, leading first to a /3-hydroxy aldehyde or ketone and then to an cr,/6-unsaturated product. Mixed aldol condensations between two different aldehydes or ketones generally give a mixture of all four possible products. A mixed reaction can be successful, however, if one of the two partners is an unusually good donor (ethyl aceto-acetate, for instance) or if it can act only as an acceptor (formaldehyde and benzaldehyde, for instance). Intramolecular aldol condensations of 1,4- and 1,5-diketones are also successful and provide a good way to make five-and six-inembered rings. 

In ToUens reaction, an aldehyde or ketone containing an a hydrogen is treated with formaldehyde in the presence of Ca(OH)2 or a similar base. The first step is a mixed aldol reaction (16-38). 

Quinone methides formed during, for example, alkaline pulping reactions may have other mechanisms for rearomatization. Most commonly, in 8-0-4-, 8-5-, and 8-8-quinone methides QM1-QM3 (Fig. 12.2), retro-aldol elimination of formaldehyde to give styryl aryl ethers or stilbenes is common.40 Retro-aldol reactions using a strong base, for example, diazabicycloundecene (DBU) in CH2CI2 can also provide these compounds conveniently at room temperatures.41 3... 

Selective retro-aldol has also been reported by using aqueous HC1 in THF.243 Recently, catalytic aldol reactions in aqueous media have generated great interest due to the atom-economy related to the reaction. Reaction of 2-alkyl-1,3-diketones with the aqueous formaldehyde using aqueous 6-10 M potassium carbonate as base afforded aldol reaction products, which are cleaved by the base to give vinyl ketones (Eq. 8.96).244... 

Sc(OTf)3 is effective in aldol reactions in aqueous media (water-THF, Scheme 15).49 Direct treatment of aqueous solutions of water-soluble formaldehyde and chloroacetaldehyde with silyl enol ethers affords the corresponding aldol adducts in good yields. Water-sensitive silicon enolates can be used in aqueous solutions in the presence of a catalytic amount of Sc(OTf)3. 

On the other hand, Ln(OTf)3 compounds, which were found to be effective catalysts for the hydroxy-methylation in aqueous media, also activate aldehydes other than formaldehyde in aldol reactions with silyl enol ethers in aqueous solvents.1121 One feature of the present reactions is that water-soluble... 

Hydroxycoumarin can be considered as an enol tautomer of a 1,3-dicarbonyl compound conjugation with the aromatic ring favours the enol tautomer. This now exposes its potential as a nucleophile. Whilst we may begin to consider enolate anion chemistry, no strong base is required and we may formulate a mechanism in which the enol acts as the nucleophile, in a simple aldol reaction with formaldehyde. Dehydration follows and produces an unsaturated ketone, which then becomes the electrophile in a Michael reaction (see Section 10.10). The nucleophile is a second molecule of 4-hydroxycoumarin. 

In addition, the isolation of 4(5)-ethylimidazole (23) from the reactions of L-rhamnose (see Table VI), L-fucose (6-deoxy-L-galactose), and 3-deoxy-L-glyceraldehyde (see Table IX) with aqueous ammonia, led Komoto and Tsuchida39 to believe that the 2-oxobutanal forming the 4(5)-ethylimidazole (23) arose from an aldol reaction of the 3-deoxy-L-glyceraldehyde (formed by dealdolization in the cases of L-rhamnose and L-fucose) with formaldehyde, with subsequent loss of water from the 4-deoxytetrose so formed. 

Phenyliodine(III) bis(trifluoro-acetate), 241 Potassium hydride, 257 (3-Hydroxy aldehydes and ketones By aldol reactions Bis(2-pyridinethiolato)tin(II), 40 Boron trichloride, 43 Formaldehyde, 136... 

The silatropic ene pathway, that is, direct silyl transfer from an silyl enol ether to an aldehyde, may be involved as a possible mechanism in the Mukaiyama aldol-type reaction. Indeed, ab initio calculations show that the silatropic ene pathway involving the cyclic (boat and chair) transition states for the BH3-promoted aldol reaction of the trihydrosilyl enol ether derived from acetaldehyde with formaldehyde is favored [60], Recently, we have reported the possible intervention of a silatropic ene pathway in the catalytic asymmetric aldol-type reaction of silyl enol ethers of thioesters [61 ]. Chlorine- and amine-containing products thus obtained are useful intermediates for the synthesis of carnitine and GABOB (Scheme 8C.26) [62],... 

Ab initio calculations on the reaction of enoxysilanes with formaldehyde have been used to characterize the electron-donating and -accepting strength of the different functions in the enoxysilane.92 This useful type of aldol reaction is also compared with the corresponding allylsilane version. 

Gung and coworkers42 have located (at the MP2/6-31 G level of theory) the transition state for the silicon-directed aldol reaction between a silyl enol ether and formaldehyde. They found it to be a boatlike six-membered ring 21 with a pentacoordinate silicon (equation 9). 

In other studies, analysis of the products of reaction between formaldehyde and guanosine at moderate pH shows a new adduct—formed by condensing two molecules of each reactant—which has implications for the mechanism of DNA cross-linking by formaldehyde,17 while the kinetics of the mutarotation of N-(/ -chlorophcnyl)-//-D-glucopyranosylamine have been measured in methanolic benzoate buffers.18 For a stereoselective aldol reaction of a ketene acetal, see the next section. 

The classic C—C bond-forming processes of aldehydes and ketones are aldol reactions. In Scheme 8.7, an iron-catalyzed sequential methanol oxidation to formaldehyde and its aldol reaction with [i-oxo ester 24a is shown [30]. The oxidant is 30% aqueous H202. Curiously for an oxidation, the reaction has to be performed under an atmosphere of Ar in order to prevent a-hydroxylation of the [i-oxo ester [31], The role of benzaldehyde (4f) as substoichiometric additive is not completely clear. 

Ab initio calculations indicate that a model uncatalysed Mukaiyama aldol reaction - that of formaldehyde and trihydrosilylenol ether - proceeds via a concerted pathway involving a twist-boat six-membered transition state.138 A wide range of substituents on both reactants have been explored, and some combinations give rise to particularly low barriers, hopefully identifying cases that should work below room temperature. 

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