Salicylic Acid in Organic Chemistry

Salicylic acid is an inorganic compound that is a type of beta-hydroxy acid (BHA) and phenolic acid with a chemical formula \[C_{7}H_{6}O_{3}\]. Salicylic acid is also known as ortho- hydroxybenzoic acid which is a white colour crystalline solid that is used for the preparation of many pharmaceutical products and one of its major products is aspirin. It is considered a free acid that occurs in small quantities in many plants and has been majorly isolated from the bark of willow trees (Salix spp.), from which it gets its name. It is considered as a plant hormone and is being listed as  EPA Toxic Substances Control Act (TSCA). 

Methyl ether which is the chief constituent of the oil of wintergreen also occurs widely in nature. An Italian chemist named Raffaele Piria developed salicylic acid from salicylaldehyde in the year 1838. Later on the German chemists Hermann Kolbe and Eduard Lautemann discovered synthetic salicylic acid-based on phenol and carbon dioxide. Today the compound is basically developed from disodium phenoxide which is also known as sodium phenolate and carbon dioxide by treating it with an acid.

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Salicylic Acid is a small aromatic acid whose chemical name is monohydroxybenzoic acid. It is lipophilic in nature. It was first derived from the bark of the Willow Tree. It derives its common name from a variety of sources related to it with a similar name, e.g., it is derived as a metabolic product of salicin (an alcoholic β-glycoside obtained from plants) and also it is an active metabolite produced from acetylsalicylic acid (aspirin). In nature, it occurs as clear and colorless crystals of an organic acid. The salt and ester derivatives of this compound are also widely used in organic chemistry and are known as salicylates. In plants, it occurs naturally as a growth hormone.

Structure of Salicylic Acid

Its structural formula is \[C_{6}H_{4}(OH)COOH,\] which can also be written as \[C_{7}H_{6}O_{3}\] in the condensed form. Its IUPAC name is 2-hydroxybenzoic acid. It contains a hydroxyl group (–OH group) attached at the ortho position with respect to the carboxylic acid functional group(–COOH group) present on the benzene ring. The molecular weight (or molar mass) of Salicylic Acid is 138.12 g/mol. The various forms in which the molecular structure of Salicylic Acid can be represented are given below:

All carbon atoms present in the benzene ring of Salicylic Acid are \[sp^{2}\] hybridized. Salicylic Acid forms an intramolecular hydrogen bond. In an aqueous solution, Salicylic Acid, being an organic acid, dissociates to lose a proton from the carboxylic acid functional group. The resulting carboxylate ion (\[–COO^{-}\]) undergoes intermolecular interaction with the hydrogen atom of the hydroxyl group (–OH), thereby leading to the formation of an intramolecular hydrogen bond.

Properties of Salicylic Acid 

Physical Properties of Salicylic Acid

• Salicylic Acid exist as clear white or colourless and odourless needle-shaped crystals at room temperature

• The taste of Salicylic Acid is acrid

• The boiling point and a melting point of Salicylic Acid are 211 °C and 315 °C, respectively

• Salicylic Acid contains two hydrogen bond donors and three hydrogen bond acceptors in its molecule

• The flashpoint of Salicylic Acid is 157 °C

• Due to its lipophilic nature, its solubility in water is very poor 

• Salicylic Acid is soluble in organic solvents such as carbon tetrachloride, benzene, propanol, ethanol, and acetone

• The density of Salicylic Acid is 1.44 at 20 °C

• Its vapor pressure is 8.2 x 10^-5 mm Hg at 25 °C

• Its LogP is 2.26

• It is a tendency to undergo discoloration when exposed to direct sunlight due to its photochemical degradation

• Upon degradation, it emits irritating fumes and acrid smelling smoke

• Its heat of combustion is 3.026mj/mole at 25 °C

• The pH of a saturated solution of Salicylic Acid is 2.4

• Its pKa (dissociation constant) is 2.97

Chemical Properties of Salicylic Acid (Reactions of Salicylic Acid)

• Formation of Aspirin: In the pharmaceutical industry, the most important reaction associated with the use of salicylic acid is the production of aspirin (acetylsalicylic acid), one of the most commonly used analgesics and blood-thinning agents. In this reaction, salicylic acid is reacted with acetic anhydride in an acidic medium which leads to the acetylation of the hydroxyl group present in the salicylic acid, thereby resulting in the production of acetylsalicylic acid (aspirin). Acetic acid is produced as a by-product of this reaction, which is also present as one of the impurities during large-scale production of aspirin and has to be removed from the resulting product mixture by several refining processes.

• Esterification Reaction: Since salicylic acid is an organic acid, it can undergo a reaction with organic alcohol groups to produce a new organic chemical class, named ester. When salicylic acid is reacted with methanol in an acidic medium (preferably sulphuric acid) in the presence of heat, a dehydration reaction occurs with the loss of water (–OH^- ion is lost from the carboxylic acid functional group present in the salicylic acid molecule and H⁺ ion is lost from the deprotonation of the methanol molecule), resulting in the formation of methyl salicylate (an ester).

Few of the Properties of Salicylic Acid is as Follows

Methods of Preparation of Salicylic Acid

There are two most commonly used methods for the preparation of salicylic acid. These methods are discussed below:

• From Phenol: When phenol is reacted with sodium hydroxide, it forms sodium phenoxide which is then further allowed to undergo distillation and dehydration. It is followed by a carboxylation reaction with carbon dioxide, which results in the formation of sodium salicylate (salt of salicylic acid). This salt form is then further reacted with an acid (or hydronium ion or any species which denotes a proton) to obtain the salicylic acid.

• From methyl salicylate: Methyl salicylate (oil of wintergreen) is also a commonly known analgesic in the pharmaceutical industry. It can be used for the preparation of salicylic acid. In this reaction, methyl salicylate is reacted with sodium hydroxide to lead to the formation of a sodium salt intermediate of salicylic acid, named disodium salicylate, which upon undergoing further reaction with sulphuric acid leads to the formation of salicylic acid.

Uses of Salicylic Acid

• Salicylic acid finds a lot of applications, particularly in the pharmaceutical industry. The most common and famous use of salicylic acid is in the preparation of an analgesic, named aspirin, which is an acetylated derivative of salicylic acid. Another analgesic formed from salicylic acid is methyl salicylate (also commonly known as the oil of wintergreen), an esterified product of salicylic acid. Both of these analgesics are widely used to treat headaches and other body aches.

• Salicylic acid is also used as a keratolytic agent. These agents are used in the form of chemical skin peeling masks to treat various types of skin lesions and outgrowths from the uppermost layer of the skin called the epidermis. It is used as an outer skin shedding agent. However, it should only be used as advised by your dermatologist as it may cause severe skin irritation in some people leading to redness, itching, and skin rashes.

• Salicylic acid also finds its use in the treatment of acne and psoriasis. The mechanism by which salicylic acid is used in the treatment of these conditions is that it loosens the keratin content in the skin by breaking the intermolecular bonds between two keratin molecules. This leads to softening of the stratum corneum layer of the skin by causing a reduction in its pH. In acne, it helps in opening the clogged pores and helps retain more moisture in the skin, thereby making skin feel better and healthier.

• Salicylic acid is used in the treatment of wart infections. The mechanism by which it treats warts infection is quite similar to its keratolytic action. It dehydrates the skin cells affected by warts when applied to it and thereby gradually leads to its shedding off from the body. Besides, it also activated the immune reaction of the body towards the viral wart infection by initiating a mild inflammatory reaction. However, it is advised by the health agencies to not use salicylic acid medications on genital warts or warts containing hair growths.

• Salicylic acid is one of the components used in anti-dandruff shampoos. It is because salicylic acid prevents the deposition of sebum in the skin pores and around hair follicles. It helps in clearing away the dead and flaky skin cells from your scalp, thereby preventing the occurrence of dandruff.

• Salicylic acid also exhibits a mild antiseptic effect since it is a known bacteriostatic agent. It does not kill the existing bacteria (and hence not an antibacterial agent) but prevents the growth of bacteria wherever applied.

• Salicylic acid also helps in the removal of blackheads and whiteheads. This is done by salicylic acid by the same mechanisms as that of acne prevention. It does not let the skin pores clog and the ones that are already clogged can be opened by the application of salicylic acid over that particular area. Skin pores basically become clogged when keratin combines with the natural oil secreted by our skin and becomes deposited in the open follicles. Salicylic acid, due to its keratolytic property, helps in the breakdown of keratin content, thereby loosening the skin’s blocked follicles which can then be easily cleaned with water. However, too much salicylic acid should not be used on the skin as it may cause hyperpigmentation in people with dark skin tones.

• Salicylic acid is also used to treat some ringworm infections and the wet form of tinea pedis infection (also known as the athlete’s foot). Salicylic acid is also used to treat a very rare genetic skin disorder, named Ichthyosis, in which skin becomes dry, scaly, and thick. The same mechanism of action (exhibited by salicylic acid) of keratolysis and skin shedding is helpful in treating all these conditions.