Salicylic acid from phenol

Figure 4.1 Synthesis of salicylic acid from phenol salt.

The manufacture of aspirin is based on the synthesis of salicylic acid from phenol. Reaction of carbon dioxide with sodium phenoxide is an electrophilic aromatic substitution on the ortho, para-directing phenoxy ring. The ortho isomer is steam distilled away from the para isomer. 

When it comes to choosing between ortho and para positions we need to consider steric effects as well. You will have noticed that we have seen one ortho selective reaction—the formation of salicylic acid from phenol—and several para selective reactions such as the bromination of an amide just discussed. 

Iijima and Yamaguchi published an efficient and regioselective carboxylation of phenol in supercritical carbon dioxide in the presence of aluminum bromide to form salicylic acid (Equation 4.31) [59]. They also reported the K2C03-catalyzed direct synthesis of salicylic acid from phenol and scC02 [60]. 

A reaction of this kind might be involved in the Barbier-Grignard reaction with the formation of salicylic acid from phenol, etc., without considering the intermediate products, but only the compositions and structures of the initial and final substances. The change involves the reduction of the carbon of the carbon dioxide and the oxidation of one of the carbon atoms of the benzene. It is exactly the same change as was shown in reaction (116) in the formation of methane and carbon dioxide from acetic acid which was shown to be an oxidation-reduction reaction. 

German organic chemist. Kolbe made many important contributions to the development of organic chemistry. These included the synthesis of ethanoic acid from completely inorganic materials, the formation and hydrolysis of nitriles, the electrolysis of solutions of fatty acid salts and the synthesis of salicylic acid from phenol and carbon dioxide. In his later years his influence had a negative effect on the development of chemistry because he opposed concepts such as structure. 

The effect of the surface area is far from being a simple one. It was shown for titania that when the surface area changes from 110 to 12 m2/g, the average time required for a complete mineralization of organic substrates increased from 40 to 75 and 50 to 75 min for salicylic acid and phenol, respectively [135], These results clearly show that textural properties, particularly the surface area, strongly affect the photoreactivity, although a high-temperature treatment improved their crystallinity [18], Therefore, this phenomenon may be explained only in connection with the catalyst surface dehydroxylation. 

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). 

In the last column of the following table, A represents the difference between the indicator constant in alcohol and in water (pAoiss. Aio. — pAdus. Water). We See from the table that, in changing from the yellow to the acid color, the dissociation constants of the sulfonephthaleins in alcohol are 10 -10 times smaller than in water. This is of the same order of magnitude as the difference exhibited by benzoic acid, salicylic acid, and phenol. 

Salicylic acid (from the Latin Sahx meaning willow tree) is a biosynthesized, organic, beta hydroxy acid that is often used. Sodium salicylate is converted by treating sodium phenolate (the sodium salt of phenol) with carbon dioxide at high pressure and temperature. Acidification of the product with sulfuric acid gives salicylic acid. Alternatively, it can be prepared by the hydrolysis of Aspirin (acetylsahcyhc acid) or Oil of Wintergreen (methyl salicylate) with a strong acid or base. 

Salicylates are derivatives of 2-hydroxybenzoic acid (salicylic acid). They were discovered in 1838, following the extraction of salicylic acid from willow bark. Salicylic acid was used medicinally as the sodium salt but replaced therapeutically in the late 1800s by the acetylated derivative, acetylsalicylic acid (ASA), or aspirin (Figure 13.2). Therapeutie utility is enhanced by esterification of the phenolic (hydroxyl) group as in aspirin, and by substitution of a hydrophobic/lipophilic group at C-5 as in diflimisal. 

The key compound in the synthesis of aspir in, salicylic acid, is prepared from phenol by a process discovered in the nineteenth century by the German chemist Hermann Kolbe. In the Kolbe synthesis, also known as the Kolbe—Schmitt reaction, sodium phen-oxide is heated with carbon dioxide under pressure, and the reaction mixture is subsequently acidified to yield salicylic acid ... 

Important chemicals derived from phenol are salicylic acid acetylsali-cyclic acid (aspirin) 2,4-dichlorophenoxy acetic acid (2,4-D), and 2,4,5-triphenoxy acetic acid (2,4,5-T), which are selective herbicides and pentachlorophenol, a wood preservative ... 

Perhaps the most widely known compound prepared from phenol is aspirin. If phenol, sodium hydroxide, and carbon dioxide are heated together under pressure, salicylic acid is formed (as the sodium salt) ... 

An additional useful test is to distil the acid or its sodium salt with soda lime. Heat 0.5 g. of the acid or its sodium salt with 0 2 g. of soda lime in an ignition tube to make certain that there is no explosion. Then grind together 0 5 g. of the acid with 3 g. of soda lime, place the mixture in a Pyrex test-tube and cover it with an equal bulk of soda hme. Fit a wide dehvery tube dipping into an empty test-tube. Clamp the tube near the mouth. Heat the soda lime first and then the mixture gradually to a dull-red heat. Examine the product this may consist of aromatic hydrocarbons or derivatives, e.g., phenol from salicylic acid, anisole firom anisic acid, toluene from toluic acid, etc. 

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