Phenol o-hydroxymethyl

Prior to 1890, formaldehyde was not commercially available [2]. Thus the first phenol-formaldehyde resins were made using formaldehyde equivalents such as methylene diacetate or methylal [2,20]. The first true phenol-formaldehyde resin was made by Kleeberg at the direction of Emil Fisher in 1891 [2,21]. Saliginen (o-hydroxymethyl phenol) was recognized as a condensation product of phenol and formaldehyde in 1894 and was the subject of United States patents in 1894 and 1896 [22,23]. 

Calix[4]arenes 97 with inherent C4 symmetry could be obtained by condensation of o-hydroxymethylated 3,4-disubstituted phenols as illustrated in Figure 17.184... 

Little is known about the overall mechanism of cyclic oligomer formation, although the mechanism of the initial stages of the sequence seems fairly clear. The first chemical event is the reaction of formaldehyde (formed in the Petrolite procedures by depolymerization of paraformaldehyde) with phenol to form 2-hydroxy-methyl- and 2,6-6w(hydroxymethyl)phenols in a base-catalyzed process, as shown in Fig. 3. Such compounds were characterized many years ago50), obtained from the action of aqueous formaldehyde on phenol in basic solution at room temperature. Subsequent condensation between the hydroxymethylphenols and the starting phenol occurs to form linear dimers, trimers, tetramers, etc. via a pathway that might involve o-quinonemethide intermediates which react with phenolate ions in a Michael-like reaction, as portrayed in Fig. 4. The condensation of hydroxymethyl-... 

A regular incorporation of the phenolic units into calix[4]arenes has been observed, if 2-or 6-hydroxymethyl derivatives of 3,4-disubstituted phenols (including cyclic compounds like S-naphthol) are condensed under these conditions (Scheme 5). The resulting calix[4]arenes 8 assume an inherently chiral, C4-symmetrical cone conformation which can be fixed by O-alkylation (see below). In an analogous manner a 2-hydroxymethyl phenol substituted at the 4-position with a porphyrin moiety has been converted to the corresponding calix[4]arene 9 in 60% yield by treatment with NaOH in refluxing diphenyl ether. ... 

Addition of formaldehyde to phenol normally produces a resin. However, under controlled, catalytic conditions, it is possible to obtain the hydroxymethyl derivatives in high yield. o-Hydroxymethyl-... 

The simplest phenolic n-glucoside is arbutin (p-hydroxyphenyl /3-d-glucopyranoside), which occurs in a number of plant species, including the pear Pyrus communis. Arbutin is usually accompanied in plant tissues by methylarbutin (p-methoxyphenyl S-D-glucopyranoside)Salix and Populus spp. contain the D-glucoside salicin, o-(hydroxymethyl)-phenyl /S-D-glucopyranoside, and certain species of poplar contain also a... 

Cross-Linker. It is well known that polyfunctional benzylic alcohols act as good crosslinkers for poly(4-hydroxystyrene) (11). This acid-catalyzed cross-linking reaction was studied in detail, and the reaction was proposed to proceed via a direct C-alkylation as well as an initial O-alkylation, followed by a subsequent acid-catalyzed rearrangement to the final alkylated product. Furthermore, both a thermal cross-linking and an acid-catalyzed cross-linking process were proposed for this alkylation (72). Thus we decided to use 4,4 -methylenebis[2,6-bis(hydroxymethyl)phenol] (MBHP) and 2,6-bis(hydroxy-methyl)phenol (BHP) in conjunction with 1 and 2, respectively, on the basis of its avail-... 

McGrath and coworkers used 2,4-bis(hydroxymethyl)phenol 19 as the adaptor unit for their dendrimer (Scheme 13). Removal of the trigger group from the 2,4-bis-(hydroxymethyl)phenol-based dendrimer subunit 14 results in a 1,6-elimination and the formation of the quinone-methide (16). The latter is trapped by an appropriate nucleophile under the reaction conditions, consistent with the electrophilic nature of quinone methides. The resulting phenol 17 (or phenoxide under basic conditions) undergoes 1,4-elimination to liberate a second equivalent of alkoxide and o-quinone methide 18 which, in turn is trapped by a nucleophile to yield the fully cleaved phenol 19. 

Cyclopropanols 72 are obtained in amazingly good yields (up to 70%) when air (or oxygen) is bubbled into ethereal solutions of cyclopropyllithiums (Scheme 1-50). or / o-Lithiated jV.A-diethylbenzamides, O-lithio benzylalcoholate, and 4-(4,4-dimethyl-2-oxazolin-2-yl)pyridine afford 2-hydroxy-benzamides 73 (Scheme 1-50), 2-(hydroxymethyl)phenol, and 3-hydroxypyridine in moderate yields (25 50%). 

Several syntheses exist for vanillin. A process recently developed by Rhodia seems to be superior [11]. The process (Scheme 5.2) involves four catalytic steps starting from phenol aromatic ring hydroxylation, O-methylation, hydroxymethyl-ation, and oxidation. The process combines elegance and precision in organic synthesis. 

AT-[(Acyloxy)methyl] derivatives of active amines and amides have the general formula RK N-CHR O-COR " where R" = H or Me (or an even larger substituent) and COR" is the acyl group. Activation of these derivatives occurs in two steps as depicted in Fig. 8.20, by analogy with the biotransformation of 0-[(acyloxy)methyl] derivatives of phenols (Sect. 8.5.6) [62], The first step is enzymatic or nonenzymatic cleavage of the ester bridge (Fig. 8.20,a), followed by chemical breakdown of the A-(hydroxymethyl) intermediate (see also Chapt. 5 in [81]). Here, again, liberation of toxic formaldehyde, i. e., where R" = H, should be avoided whenever possible by substitution of, e.g., Me at R"... 

Cyclizations of o-(a -haloalk oxy)phenols have been widely studied and were used to afford an expedient synthesis of 5-alkyl-2,3-dihydro-l,4-benzodioxins <2004SC2487>. This approach via a nucleophilic substitution was used for the synthesis of 8-substituted-2-hydroxymethyl-l,4-benzodioxane derivatives 164 in an enantiopure form. Use of CsF instead of more basic conditions allowed higher yields and enantiomeric excess (Equation 28) <2001ASC95>. Dry tetrabutylammonium fluoride (TBAF) in THF was required and was basic enough to initiate an intramolecular Sn substitution from the protected phenol 165 to the fluoro-l,4-benzodioxane 166 <1996T6187>. 

In addition to acting as a crosslinking site, the hydroxymethyl group and unsubslituled o and p positions may be used as reactive sites to join numerous other compounds to the phenolic polymer, These modified resins often possess many properties normally not attributable tn phenolics in the unaltered slate. 

Benzylic cations have also been implicated in the formation of phenol-formaldehyde polymers. The synthesis of phenol-formaldehyde polymers, including the involvement of carbocations, has been reviewed [39], The involvement of benzylic cations in this reaction sequence is shown in Fig. 14. The first step of the acid-catalyzed reaction is the formation of a hydroxymethyl carbocation. Electrophilic substitution of phenol produces an o- or p-hydroxymethylphenol 91. Rapid protonation of the hydroxymethyl, followed by loss of H20, results in the formation of benzylic... 

An unusual extension of hydroboration involves remote C H activation. Aryl alkenes are treated with borane and then oxidized in the usual manner. The product is a phenol and a hydroxymethyl group (Ph C=C CH3 o-Ph-CH-CH-CH20H. ... 

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