Hydroxybenzyl alcohol derivatives

A B—0 bond is broken in the case of phenylboron derivatives of o-hydroxybenzyl alcohol (147) where the loss of PhBO is observed,... 

Numerous methods for the synthesis of salicyl alcohol exist. These involve the reduction of salicylaldehyde or of salicylic acid and its derivatives. The alcohol can be prepared in almost theoretical yield by the reduction of salicylaldehyde with sodium amalgam, sodium borohydride, or lithium aluminum hydride by catalytic hydrogenation over platinum black or Raney nickel or by hydrogenation over platinum and ferrous chloride in alcohol. The electrolytic reduction of salicylaldehyde in sodium bicarbonate solution at a mercury cathode with carbon dioxide passed into the mixture also yields saligenin. It is formed by the electrolytic reduction at lead electrodes of salicylic acids in aqueous alcoholic solution or sodium salicylate in the presence of boric acid and sodium sulfate. Salicylamide in aqueous alcohol solution acidified with acetic acid is reduced to salicyl alcohol by sodium amalgam in 63% yield. Salicyl alcohol forms along with -hydroxybenzyl alcohol by the action of formaldehyde on phenol in the presence of sodium hydroxide or calcium oxide. High yields of salicyl alcohol from phenol and formaldehyde in the presence of a molar equivalent of ether additives have been reported (60). Phenyl metaborate prepared from phenol and boric acid yields salicyl alcohol after treatment with formaldehyde and hydrolysis (61). 

The northeast Pacific bryozoans Phidolopora pacifica contained two nitrophenols, desmethylphidolopin (448) and 3-nitro-4-hydroxybenzyl alcohol (449) (365). Desmethylphidolopin (448) showed antimicrobial activity. 2-Amino-6-[(r/ ,2 5)-l, 2 -dihydroxypropyl]-3-methyl pterin-4-one (450) was isolated from the anthozoan Astroides calycularis collected in the Bay of Naples and exhibited cell growth-inhibiting activity (366). The structure of leucettidine, a pteridine derivative found in Leucetta microra-... 

Hydroxyisocoumarins are accessible from 3-hydroxybenzyl ketones using directed lithiation as the key step (95G 111) and isocoumarins have been prepared from 2-iodobenzoic acid and alkynes through a Pd-mediated annulation (95JOC3270, 3711). The cyclisation of tertiary alcohols derived from the reaction of o-cyanobenzyllithium with aldehydes and ketones yields 3,4-dihydroisocoumarins (95S1102). 

Both routes actually use vanilly alcohol 34 (3-methoxy-4-hydroxybenzyl alcohol) as the starting material. Application of method (a) requires that 34 could be trimerized to C3-cyclotriguaiacylene, 5 (Table 1). However, as was said above, this reaction does not work, presumably because the phenolic group makes the molecule too reactive under the strong acidic conditions employed the allyl protected derivative 35 was thus used instead of 34 itself, and, on reaction with perchloric acid in methanol, gave the tris-allyl protected derivative 9 in 55% yield. Palladium catalysed cleavage of the allyl groups then led to the desired racemic triphenol 5. The latter could eventually be resolved by separation of its dia-stereoisomeric esters with co-camphanic acid [13]. 

The formation of the isomers of the quinonemethide (131) by irradiation of the corresponding o-hydroxybenzyl alcohol has been described. A further study on the formation and reactivity of quinone methides has reported the flash photolysis of the phenol derivative (132) in perchloric acid solution. This affords the p-quinone methide (133). Irradiation of the benzene derivative (134) results in the formation of the quinodimethane (135). A two-colour laser method... 

Oxidation of substituted benzyl alcohols to the corresponding aldehydes has been patented [102-107]. Oxidation of 3-hydroxybenzyl alcohol in alkaline solution over Pt- and/or Pd-type catalysts yielded 3-hydroxybenzaldehyde with high selectivity [103]. An alcohol and a tertiary ammonium salt were used to control formation of by-product 3-hydroxybenzoic acid. Oxidation of 2-hydroxybenzyl alcohol in aqueous basic medium in the presence of Pt and B and Bi derivatives (H3BO3 and Bi203) gave 97 % of the corresponding aldehyde (salicylaldehyde)... 

A completely purified halogenating enzyme has not been isolated from marine sources, but the existence of haloperoxidases has been securely established. Pedersen (1976) succeeded in demonstrating the existence of a brominating cind hydroxylating enzyme in the red alga Cystoclonium purpureum, and Manley (1977) has recently illustrated the in vitro bromina-tion of precursor molecules in cell-free extracts of the red alga Odonthalia floccosa. Both enzymes were found to catalyse the bromination of phenolic precursors such as p-hydroxybenzyl alcohol (55) to yield the halo derivatives as in 56. 

Salicylic Acid, HO.C6H4.COOH(l, 2), is the most important hydroxybenzoic acid. It derives its name from salicin, a glucoside obtained from the bark of the willow salix) which yields glucose and o-hydroxybenzyl alcohol on hydrolysis. 

While PEGS can themselves serve as phase-transfer catalysts [86], onium salts are generally more effective as catalysts. Using the chemistry shown in Eq. 18, a methoxy-PEG5ooo derivative 47 was first treated with the Cs salt of 4-hydroxybenzyl alcohol to form the alcohol 48. Conversion of the alcohol to the bromide followed by reaction with tributylamine produced a quaternary ammonium salt 49. This salt was as active as low molecular weight salts in typical phase-transfer catalyzed reactions like those of alkyl halides with KI, KCN, phenol, and pyrrole [88]. Yields were often in the >90% range. Reactions were typically carried out at <40 °C and could be performed either with water or without solvent. Control experiments showed that the ammonium group of 49 was necessary as the simple alcoholic PEG derivative 48 was much less effec-... 

Tadesse and coworkers assumed that pulmonarins and synoxazolidinones share the common biosynthetic route in the organism [15]. Pulmonarin A (19) had been considered as a dibrominated form of />-hydroxybenzoylcholine, which biosynthetically derived from p-hydroxybenzyl alcohol [16, 17]. According to the proposed biosynthesis dibromo hydroxybenzyl alcohol 21 get oxidized and methylated before coupling with choline 24 (Scheme 3). The biosynthesis of pulmonarin B (20) was assumed via the coupling of known metabolites 2-(3,5-dibromo-4-methoxyphenyl)acetic acid 25 [11] and ascophylline 26 [18]. 

No new TV-benzyltetrahydroisoquinolines have been isolated from natural sources in recent years. However, the structure of corgoine has been confirmed by three syntheses. The first involves reduction of the 7V-benzyl quaternary salt derived from isoquinoline 1, whereas the second approach utilizes the Pictet-Spengler reaction to cyclize the substituted phenethylamine 2 (see Scheme 31.1). The third synthesis of corgoine involves heating 6-methoxy-7-hydroxy-tetrahydroisoquinoline with / -hydroxybenzyl alcohol to afford the alkaloid in 44% yield. The A -benzylation probably occurs through the intermediacy of /7-benzoquinone methide which adds to the basic nitrogen of the isoquinoline. ... 

Aromatic and heterocyclic isothiocyanates are unstable and easily hydrolyse to the corresponding alcohols. For example, 4-hydroxybenzyl isothiocyanate (the degradation product of sinal-bin, which occurs in the seeds of white mustard, Leucosinapis album, Brassicaceae) decomposes in normal table mustard to 4-hydroxybenzyl alcohol and thiocyanate ions (Figure 8.68). Isothiocyanates derived from indolyl glucosinolates behave similarly. 

TABLE 1 is a summary of toxicity data for the 15 derivatives which form the initial data set. Toxicity varies over approximately two orders of magnitude. The phenoxy derivative is the most toxic. The 4-hydroxybenzyl alcohol does not elicit an IGC50 at saturation. In all cases, the data fit the probit model extremely well with Pgreater than 0.9000, based on n >20. 

The log BR and molecular descriptor values for the initial data set are presented in TABLE 2. The r ranking of the 16 single independent variables is listed in TABLES. Due to two missing (7p values and one missing value, as well as the lack of toxicity of 4-hydroxybenzyl alcohol, only 11 derivatives of the initial set were included in this analysis. MR is the best single descriptor, followed by log In an effort to increase the data set to 14 derivatives, the (Tp", ap" , R" and R" " electronic descriptors were deleted. The results of the single descriptor re-evaluation of these data are also presented in TABLE 3. 

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. 

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