Reaction with saligenin

Reactions. Saligenin [90-01-7] undergoes the typical reactions of phenols and benzyl alcohol. When heated above 100°C, it transforms into a pale yellow resinous material. Amorphous condensation products are obtained when saligenin reacts with acetic anhydride, phosphoms pentachloride, or mineral acids. Upon boiling with dilute acids, saligenin is converted into a resinous body, saliretin, a condensed form of saligenin. Condensation reactions of saligenin with itself in the absence of any catalysts and in the presence of bases have also been studied. 

Reactions with Model Compounds. To test whether carbohydrates were actually reacting with the phenolic resin, the reaction of methyl xyloside (III) and saligenin (V) under neutral conditions was studied. This reaction system was used as a model for the curing reaction. 

Figure 5. TLC on Whatman K5F silica gel of (1) the reaction mixture of saligenin and methyl xyloside heated at 140 °C for 80 minutes and (2) the reaction of saligenin with itself when heated at 140 °C for 60 minutes. The TLC plate was developed in 8% methanol in chloroform and visualized by spraying with 50% concentrated sulfuric acid in ethanol and heating at 140 °C.

The main processes for the manufacture of hydroxybenzaldehydes are based on phenol. The most widely used process is the saligenin process. Saligenin (2-hydroxybenzyl alcohol [90-01-7]) and 4-hydroxybenzyl alcohol [623-05-2] are produced from base-catalyzed reaction of formaldehyde with phenol (35). Air oxidation of saligenin over a suitable catalyst such as platinium or palladium produces sahcylaldehyde (62). 

Although 4-hydroxybenzaldehyde can be made by the saligenin route, it has been made historically by the Reimer-Tiemann process, which also produces sahcylaldehyde (64). Treatment of phenol with chloroform and aqueous sodium hydroxide results in the formation of benzal chlorides, which are rapidly hydrolyzed by the alkaline medium into aldehydes. Acidification of the phenoxides results in the formation of the final products, sahcylaldehyde and 4-hydroxybenzaldehyde. The ratio of ortho and para isomers is flexible and can be controlled within certain limits. The overall reaction scheme is shown in Figure 1. Product separation is accomphshed by distillation, but this process leads to environmental problems because of the quantities of sodium chloride produced. 

The 1H-NMR and 13C-NMR spectra were obtained for each of the three components. The spectra of the components are compared with those of methyl xyloside and saligenin in Tables I and II. The spectra are consistent with the three components having been formed by the reaction of one hydroxyl substituent on methyl xyloside with the methylol group of saligenin to form an ether linkage. Formation of similar compounds has been reported on reacting carbohydrates with vanillyl alcohol (12). 

Saligenin (76) is photochemically reactive (254 nm) when irradiated in basic media (MeOH/HeO). The reaction affords phenol/formaldehyde type resins in reasonable yield. The route to the condensation process involves the formation of the enone (77) by photochemically induced expulsion of hydroxide from the phenolic anion generated from (76). This enone then reacts with another anion ultimately to build up oligomers. Evidence for this process comes from the minor products formed during the reaction. These are the ether (78) which is produced by the addition of methanol (the solvent) to the enone (77). Furthermore the diphenylmethane derivatives (79) and (80) are also formed by the condensation of two substrate molecules either with or without the addition of solvent. Products of this type are considered as good evidence for the condensation reaction proposed. ... 

Among hydroxybenzaldehydes, the o- and p- hydroxy isomers are the most important for commercial applications in agricultural, flavor and fragance, pharmaceutical or polymer fields (ref. 1). The two main processes for the manufacture of hydroxybenzaldehydes are both based on phenol. The most widely used process is the saligenin process. Hydroxybenzyl alcohols (o- and p- isomers) are produced from base - catalyzed reaction of formaldehyde with phenol (ref. 2). Air oxidation of these alcohols over a suitable catalyst (based on palladium or preferentially on platinum) produces hydroxybenzaldehydes (ref. 3). The Reimer -Tiemann process allows the coproduction of o- and p- hydroxybenzaldehydes (ref. 4). Treatment of phenol with aqueous chloroform and sodium hydroxide leads to benzal chlorides which are rapidly hydrolyzed by alkaline medium to aldehydes. The previous processes need two chemical steps and produce salt effluents. 

Unfortunatly, oxidation of 2-methylphenol with the previous catalysts (Pd-Sn/C and Pd/C) only gives small amounts of 2-hydroxybenzoic acid and heavies (table 2, entry 10). These heavies are polyethers probably obtained by reaction of o-cresol itself with 2-hydroxybenzylacetate or 2-hydroxybenzylalcohol. Apparently, palladium catalysts activate the benzylic C-H bond of o-cresol, but the oxidation of the intermediates seems less rapid than side reactions. On the other hand, we have check that platinum catalysts, which are known to be excellent catalysts for the oxidation of 2-hydroxybenzylalcohol into 2-hydroxybenzaldehyde in basic aqueous medium (ref. 3), is unable to activate efficiently the benzylic C-H bond of cresols. We synthesized bimetallic catalysts, Pd-Pt / C, with the hope that palladium would activate benzylic C-H bond and platinum would accelerate the oxidation of intermediate alcohols. Effectively, this new catalyst allows to recover 2-hydroxybenzaldehyde with 14 % selectivity at 70% conversion (Table 2, entries 11-12). Addition of bismuth salts are known to improve the aldehyde yield in the saligenin process. With such additives, the selectivity of the aldehyde can reached 60% for a total cresol conversion. Of course Pd-Pt / C can also oxidize 4-methylphenol but it does not bring significant improvement compared to initial catalysts. 

The use of these intermediates to produce shikimates is shown in Figure 6.32. In principle, anethole (53) and estragole (methyl chavicol) (52) are available from phenol, but in practice, the demand is met by extraction from turpentine. Carboxylation of phenol gives salicylic acid (38) and hence serves as a source for the various salicylate esters. Formylation of phenol by formaldehyde, in the presence of a suitable catalyst, has now replaced the Reimer-Tiemann reaction as a route to hydroxybenzaldehydes. The initial products are saligenin (189) and p-hydroxybenzyl alcohol (190), which can be oxidized to salicylaldehyde (191) and p-hydroxybenzaldehyde (192), respectively. Condensation of salicylaldehyde with acetic acid/acetic anhydride gives coumarin (50) and 0-alkylation ofp-hydroxybenzaldehyde gives anisaldehyde (44). As mentioned earlier, oxidation of phenol provides a route to catechol (184) and guaiacol (188). The latter is a precursor for vanillin, and catechol also provides a route to heliotropin (61) via methylenedioxybenzene (193). 

A two-stage reaction has been used by Higginbottom to obtain higher molecular weight resoles by treating an acid-catalyzed novolac with more formaldehyde and a basic catalyst.A comprehensive description of the earlier work on self-condensation of saligenin can be found in books by Megson " and Martin. ... 

In 1843, Pira [1] reported that phenol alcohols are converted to resins (called saliretins) on heating. Baeyer [2] in 1872 reported that the reaction of phenols with acetaldehyde in the presence of acid catalysts also gives resinous products. Kleeberg [3] in 1891 reported that formaldehyde undergoes similar reactions. However, Dianin [4, 5] found that acetone reacts with phenol to give a crystalline bisphenol (now known as bisphenol A). In 1874 Lederer [6] and Manasse [7] independently synthesized o-hydroxybenzyl alcohol (saligenin) by the low-temperature alkaline-catalyzed formaldehyde reaction. 

Saligenin, the parent of the ortho-substituted hydroxymethyl phenols, is prepared by the low-temperature reaction of equimolar amounts of phenol and formaldehyde using calcium hydroxide catalyst [94]. Zinc acetate can be used with excess phenol to give a 53 7o yield of saligenin, m.p. 86 C, after precipitation from carbon tetrachloride [95]. The product is not stable for long periods of time at room temperature and must be kept refrigerated. Exposure of saligenin to air will cause the sample to resinify, possibly because of contamination by acidic impurities. 

Salicylaldehyde and Raney alloy added alternately during 30 min. with stirring to ice-cooled aq. NaOH at such a rate that the temp, is kept below 20, stirring continued for 30 min. saligenin. Y 77%.—Similarly at 90° (s. a. Synth. Meth. 4, 102) -> o-cresol. Y 76%.—Reduction either to alcohol or hydrocarbon groups can be achieved by proper choice of the reaction temp. F. e. s. P. L. Cook, J. Org. Chem. 27, 3873 (1962). 

Carletti, E., Schopfer, L.M., Colletier, J.P., et al., 2011. Reaction of cresyl saligenin phosphate, the organophosphorus agent implicated in aerotoxic syndrome, with human cholinesterases mechanistic studies employing kinetics, mass spectrometry, and X-ray structure analysis. Chem. Res. Toxicol. 24, 797-808. 

A widely used industrial process for the production of salicylaldehyde is the Saligenin process that produces hydroxybenzyl alcohols (o- and p-isomers) from the base-catalyzed reaction of formaldehyde with phenol, followed by oxidation using a palladium or platinum catalyst to produce the hydroxybenzaldehyde (Eq 1 44) 129,130.131... 

This reaction is effected by heating a suspension of beta-naphthol in water vitli equivalent quantities of formaldehyde and sodium bisulfite. The sulfo acid is reported to ciystallize from solution on cooling after acidifica tion with acetic acid. The formation of this sulfonate of a naphthol analogue of saligenin is of particular interest, since monomethylolnaphthols haw never been isolated. 

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