Para-Hydroxybenzyl

The absence of methylol (-CH2OH) groups in all six lower molecular weight resorcinol-formaldehyde condensates which have been isolated [119] reflects the high reactivity of resorcinol under acid or alkaline conditions. It also shows the instability of its para-hydroxybenzyl alcohol groups and their rapid conversion to jpara-hydroxybenzyl carbonium ions or quinone methides. This explains how identical condensation products are obtained under acid or alkaline reaction conditions [119]. In acid reaction conditions methylene ether-linked condensates are also formed, but they are highly unstable and decompose to form stable methylene links in 0.25 to 1 h at ambient temperature [121,122]. 

In one model reaction where tris(para-hydroxybenzyl)amine was heated to 205°C in the presence of 2,4-xylenol (1 1 ratio), the ortho-ortho, ortho-para,... 

Sodium metabisulfite reacts with sympathomimetics and other drugs that are ortho- or para-hydroxybenzyl alcohol deriva-... 

Further investigation of the complex fragmentation behaviour of the steroid [M — H] ions led to the study of simpler model systems, viz. fatty acid esters containing a para-hydroxybenzyl (cf. 138, Scheme 37) or /3-(para-hydroxy)phenethyl moiety . Again, the formation of intermediate anion/molecule complexes was demonstrated by the course of collision-induced dissociation of various deuterium-labelled [M — ions, where... 

Figure 5 Log of reaction rate constant versus jT T in kelvins) for the reaction of ortho and para hydroxybenzyl alcohol with urea, detailing the relative rates of condensation with urea of ortho and... 

Scheme 8.44. The reaction of formaldehyde with the phenoxide anion to produce ortho- and para-hydroxybenzyl alcohols. Acidification leads to benzyhc carbocations (an El elimination), which react with more formaldehyde, phenols, and substituted phenols to produce a formaldehyde-phenol resin-type polymer.

Yield.—Including both compounds, 80% theoretical (32 gms.). o-Hydroxybenzyl alcohol (saligenin) forms colourless crystals M.P. 82° the para-compound melts at 112°. (B., 27, 2411.)... 

The reactivity of the hydrocarbons increases in the order ortho < meta < para in the liquid-phase catalytic oxidation of methyl derivatives of biphenyl into acids by air. The mechanism of the oxidation of hydroxymethylbiphenyls and hydroxymethyl-benzenes involves the formation of an unstable cation radical, which is then stabilized by emitting a proton, giving hydroxybenzyl radical.243... 

In contrast to aliphatic alcohols, which are mostly less acidic than phenol, phenol forms salts with aqueous alkali hydroxide solutions. At room temperature, phenol can be liberated from the salts even with carbon dioxide. At temperatures near the boiling point of phenol, it can displace carboxylic acids, e.g. acetic acid, from their salts, and then phenolates are formed. The contribution of ortho- and -quinonoid resonance structures allows electrophilic substitution reactions such as chlorination, sulphonation, nitration, nitrosation and mercuration. The introduction of two or three nitro groups into the benzene ring can only be achieved indirectly because of the sensitivity of phenol towards oxidation. Nitrosation in the para position can be carried out even at ice bath temperature. Phenol readily reacts with carbonyl compounds in the presence of acid or basic catalysts. Formaldehyde reacts with phenol to yield hydroxybenzyl alcohols, and synthetic resins on further reaction. Reaction of acetone with phenol yields bisphenol A [2,2-bis(4-hydroxyphenyl)propane]. 

The first two prodrugs we prepared using this concept 13 and 14, associated a-D-galactose as specifier with a para- or ortho-hydroxybenzyl spacer linked to daunorubicin through a carbamate group (54-55). 

Another spiro compound has been obtained from the oxazolidine illustrated by the use of essentially the same reagent (ref.78). N-3-trichloroethoxycarbonyl-(2R)-4-hydroxybenzyl-(5S)-3,4-dimethoxyphenyloxazolidineindichloromethane upon treatment with vanadium oxyfluoride in trifluoroacetic/trifluoroacetic anhydride at -78 to-10 C afforded the para-para coupling product. 

In the light of the ease of dealkylation of di-fcr butyl esters of quinquevalent phosphorus acids, either thermally or under acid catalysis, the reaction between di- er -butyl hydro-genphosphonate and 4-(diethoxymethyl)benzaldehyde has been employed to yield, after deprotection of the para substituent, the (a-hydroxybenzyl)phosphonic diester 169, useful for classical development at the aldehyde group ... 

When phenol is carefully treated under basic conditions with formaldehyde (H2CO), substitution occurs at positions ortho and para to the phenolic hydroxyl (-OH). In this way, hydroxybenzyl alcohols (Scheme 8.44) can be produced. Acidification results in the generation of the respective stabilized benzylic carboca-tions (an El reaction, Chapter 7), which can then react with unreacted phenol and/... 

A series of oligomeis based upon 2,6-fused diphenylmethane units is derived from the acid-catalyzed condensation of 2-hydroxybenzyl alcohols (or closely related compounds). Halogens can be usefully employed to protect the position para (and thus direct condensation ortho) to the hydroxyl group and to act as end stoppers or to bring about controlled chain elongation e.g. Fig. 1.26. 

The reaction mechanism for the basic catalysis of phenolics is not completely understood. However, the reaction kinetics are known to be first order in methylene glycol and in phenol. A complete comparison of the relative reaction rates of producing the seven possible methylol phenols is given by Knop and Pizzi. Table 3 shows the rate constants,the relative rate constants compared to 4-hydroxymethyl phenol (4-HMP) and the relative rate constants after allowing for the statistical weighting of the two ortho positions in both phenol and 4-hydroxy-methylphenol. Comparison of kinetic rate constants for formaldehyde addition in the ortho positions relative to the kinetic rate constant for the addition of formaldehyde to phenol in the para position shows that the formation of 2-hydroxybenzyl alcohol is favored over 4-hy-droxybenzyl alcohol 1.7 1. The formation of the 2,4-dihydroxymethylphenol (2,4-HMP) is 1.2 1 compared to the formation of 2,6-dihydroxy methylphenol at 1.40 1. Interestingly, the 2,4,6-trihydroxy methylphenol (2,4,6-... 

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