Hydroxymethyl Group

Hydroxymethylpyridazines are easily oxidized with selenium dioxide to the corresponding aldehydes. Oxidation of the corresponding secondary alcohols with chromic acid in aqueous sulfuric acid gives ketones, while oxidation of a hydroxymethyl group with permanganate leads to the pyridazinecarboxylic acids. Hydroxymethyl groups are converted into chloromethyl groups with thionyl chloride or phosphorus oxychloride. 

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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). 

The first step in the formation of resins and plastics from formaldehyde and amino compounds is the addition of formaldehyde to introduce the hydroxymethyl group, known as methylolation or hydroxymethylation ... 

N,]S7-bis(methoxymethyl)uron was first isolated and described in 1936 (41), but was commercialized only in 1960. It is manufactured (42) by the reaction of 4 mol of formaldehyde with 1 mol of urea at 60°C under highly alkaline conditions to form tetramethylolurea [2787-01-1]. After concentration under reduced pressure to remove water, excess methanol is charged and the reaction continued under acidic conditions at ambient temperatures to close the ring and methylate the hydroxymethyl groups. After filtration to remove the precipitated salts, the methanolic solution is concentrated to recover excess methanol. The product (75—85% pure) is then mixed with a methylated melamine—formaldehyde resin to reduce fabric strength losses in the presence of chlorine, and diluted with water to 50—75% soHds. Uron resins do not find significant use today due to the greater amounts of formaldehyde released from fabric treated with these resins. 

The mixture is refluxed until the reaction has proceeded sufficiently. It may then be neutralised and the water formed distilled off, usually under reduced pressure to prevent heat-hardening of the resin. Because of the presence of hydroxymethyl groups the resol has a greater water-tolerance than the novolak. 

Fig. 6. Freeman and Lewis stabilized structure and the likely results of orr/to-polymerization. As polymerization consumes o-hydroxymethyl groups, the hydrogen-bonded species cannot fomi.

Scheme 4b depicts condensation between a hydroxymethyl group and a phenolic ring where the hydroxybenzyl attacks at a ring position that is already hydroxymethylated. In this case, a methylene linkage is produced between the rings with concurrent loss of one mole each of formaldehyde and water. Both Jones and Grenier-Loustalot et al. demonstrated the occurrence of this reaction pathway beyond doubt under basic conditions. 

Kim et al, observed a number of facts gleaned from C-NMR that led to an overall picture of the reactivity of various hydroxymethyl phenols (HMPs) [144, 148], Grenier-Loustalot and co-workers did a number of important experiments that expanded Kim s findings and clearly delineated the reactivity of the various functional groups position-by-position [128], The two studies show excellent agreement. The materials that follow are drawn from these two reports without further citation. As shown in Scheme 5, the condensation of 2-HMP at pH 8 and 60°C resulted in only one product. This product is the result of p-attack on the ring by the hydroxymethyl group. 

Several products resulted when 4-HMP was allowed to condense under the same conditions. These are provided in Scheme 6. These products indicate that a p-hydroxymethyl group can react with either an unsubstituted ortho position or through an ipso-attack on a hydroxymethyl-substituted para position. The two condensation products were formed at approximately equal rates. Since there were two unoccupied orthos, it seems that the specific reaction rate for the ortho site is about half that of the occupied para position in this situation. The condensation rate for 4-HMP was about 5 times the rate for 2-HMP overall. 

Scheme 11. Proposed quinone methide condensation mechanism. Work by Murray (and Lemon unpublished) showed clearly that the quinone methides formed from o-hydroxymethyl and not /7-hydroxymethyl groups in the presenee of ester.

Tomoi, Kihara and Kakiuchi " have prepared a cryptand with a hydroxymethyl group in one of the strands and then utilized this as nucleophile in a reaction with chlo-romethylated polystyrene. The type of compound prepared by this method is illustrated in Eq. (8.16). 

A one-pot conversion of benzyl alcohols to benzyl fluorides by treatment of the alcohols with a combination of methanesulfonyl fluoride, cesium fluoride and 18-crown 6 ether in tetrahydrofuran has been repotted The reaction involves mesylation of the alcohols followed by cleavage of the resultant mesyl esters with a fluoride ion The reaction has been extended also to certain heterocycles bearing the N hydroxymethyl group [43] (equation 31)... 

The hydroxymethyl group m 3-(perfluoro-l,l-dimethylbutyl)propan-l-ol is oxidized to a carboxylic group by potassium permanganate m the presence of a phase-transfer catalyst [3d] (equation 41)... 

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)... 

The 2,7-naphthyridine system 53 (Scheme 8.4.18) was combined with 2,4-dinitrochlorobenzene and 2-amino glycerol for in situ reaction of the resulting Zincke salt. The resulting naphthyridinium 54 was trapped by Bradsher cycloaddition with (Z)-vinyl ether 55, providing tetracycle 56 (X-ray) upon internal addition of one of the diastereotopic hydroxymethyl groups to the resulting iminium. This approach was also extended to the use of chiral 2,7-naphthyridinium salts, prepared via the analogous Zincke process. ... 

Methoxymethyl group of perhydro[l,2]oxazino[3,2-7]quinolin-6-one 21 (R = MOM) was converted to a hydroxymethyl group by treatment with a boiling mixture of cone. HCl and MeOH, and the hydroxymethyl group was benzylated with PhCH Br in the presence of NaH and BU4NI in DMF at room temperature (00JA4583). 

In d sumldf way, a-nitroselenides are prepared via the reacdon of nitronates with phenylse-lenyl bromide, which gives a new synthedc method of 1-nitroalkenes from nitroalkanes The sequence of ct-selenadon, nitro-aldol reacdon, and oxidadon provides a nsefid method for the preparadon of nitroalkenes with a hydroxymethyl group fEq 5 81 ... 

All of these ehimnddon reacdons contain fi-carbonyl groups in the nltro compounds Of course, masked carbonyl groups are also frequently employed for such fi-elimination of HNO, as shown in Eq 7131, Eq 7 133, and Eq 7 133In these cases, the sulfinylmethyl or hydroxymethyl group is converted into the carbonyl group by the Pummerer rearrangement or by simple oxidation... 

Dilute hydrochloric acid reacts with the methoxymethyl derivative 6 to give the hydroxymethyl compound 7. The hydroxymethyl group of the latter can be removed by treatment with ammonia solution to give ethyl 5-oxo-4,5-dihydro-177-1,4-diazepine-l -carboxylatc (8).31... 

Condensation reactions between two hydroxymethyl substituents eliminate water to form ether linkages (Fig. 7.23a) or eliminate both water and formaldehyde to form methylene linkages (Fig. 7.23b). Ether formation is favored under neutral or acidic conditions and up to 130°C above which formaldehyde departs and methylene linkages are generated. The methylene linkage formation reaction, which eliminates water and fortualdehyde, is more prevalent under basic conditions. Condensation reactions between hydroxymethyl groups and reactive... 

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