Salicylal Saligenin

In the following experiment, salicylic acid is reduced to o-hydroxybenzyl alcohol (or saligenin), which being crystalline is readily isolated the excess of hydride is destroyed by the addition of undried ether, and the aluminium hydroxide then brought into solution by the addition of sulphuric acid. 

Salicylic alcohol glucosides, natural, 22 7 Salicyloyl chloride, 22 3 Salicylsalicylic acid, 22 16-17 physical properties of, 22 15t Saligenin, 22 23, 24 Salina salt, 5 788 Saline hydrides, 13 771 Saline solutions... 

Salicyl alcohol [90-01-7] (saligenin, 0-hydroxybenzyl alcohol) crystallizes from water in the form of needles or white rhombic crystals. It occurs in nature as the bitter glycoside, salicin [138-52-3], which is isolated from the bark of Salix helix, S.pentandra, S.praecos, some other species of willow trees, and the bark of a number of species of poplar trees such as Polpulus balsamifera, P. candicans, and P. nigra. 

Oxidation of saligenin with chromic acid or silver oxide yields salicyladehyde as the first product. Further oxidation results in the formation of salicylic acid, which is also obtained when saligenin is heated with sodium hydroxide at 200—240°C. Chlorination of an aqueous solution of the alcohol gives 2,4,6-trichlorophenol, and bromination in an alkaline medium yields 2,4,6-tribromophenol and tribromosaligenin. When saligenin is heated with one mole of resorcinol in the presence of anhydrous zinc chloride, 3-hydroxyxanthene forms. 

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). 

For many decades the pain relieving properties of willow bark extracts have been used in folk medicine (Fig. 1). Glycoside cleavage and oxidation is necessary for the biosynthesis of salicylic acid from the plant precursor p-D-glucopyranoside, the so-called saligenins. 

Salicin.—It derives its name from the glucoside salicin which is present in the bark of willow trees, the generic name of which is Salix, When the glucoside is hydrolyzed it yields glucose and a compound known as saligenin, which is salicylic alcohol or ortho-hydroxy benzyl alcohol, and which on oxidation yields salicylic acid. This is one of the natural sources of the acid. 

FIGURE 1. Salicin, saligenin, salicylic acid, and aspirin... 

The onset of the antiinflammatory effect of willow bark constituents is delayed in comparison with that saligenin (salicyl alcohol), sodium salicylate and acetylsalicylic acid, indicating that metabolites of willow constituents may be the active principles. 

Salicin—Saliciruim C. S,)——2SG—occurs in the bark of the willow (saZio ). It is a white, crystalline Substance insoluble in ether, soluble in water and in alcohol very bitter, its solutions are dextrogyrous, + 55. 8, Dilute acids decompose it into glucose and saligenin (q. u). Concentrated H.,SO colora it red, the color being discharged on the adch-tion of water. When taken into the economy it is converted into salicylic aldehyde and acid, which are eliminated in the urine. 

Improvements in the regiospecific synthesis of salicyl aldehyde have been made by the same group who earlier (ref.1) devised a novel route to saligenin. Salicylaldehyde can be obtained in 99% yield by the reaction of phenol in... 

No gastric injury was observed after administration of a single dose of 5 mmol/kg salicin to rats. In the same study, saligenin and sodium salicylate induced severe gastric lesions (Akao et al. 2002). 

Salicyl alcohol (saligenin, 2-hydroxybenzyl alcohol). C7H8O2, Mr 124.14, needles (from water) or plates (from ether) with a burning taste, mp. 86 °C, subl. 100 °C occurs in nature in the form of glycosides, see table. 

So, how does willow baik compare to acetyl salicylic acid The baric contains 1-2 % of salicyl derivatives, most of them as glycosides. The main ingredient is salicin (Fig. 3.42), which is also responsible for the bitter taste. In the intestine, sali-cin is solely hydrolyzed to give saligenin (salicyl alcohol), which turns into salicylic acid in the blood stream. The actual anti-inflammatoiy effect belongs to salicylic acid. 

Fig. 3.42 Chemical structures of salicin, saligenin and salicylic acid. (Authors own work)...

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