Salicylic acid

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Salicylic acid
Skeletal formula of salicylic acid
Skeletal formula of salicylic acid
Ball-and-stick model of salicylic acid
Ball-and-stick model of salicylic acid
Salicylic acid
Names
Preferred IUPAC name
2-Hydroxybenzoic acid[1]
Identifiers
3D model (
JSmol
)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard
 100.000.648 Edit this at Wikidata
EC Number
  • 200-712-3
IUPHAR/BPS
KEGG
RTECS number
  • VO0525000
UNII
  • InChI=1S/C7H6O3/c8-6-4-2-1-3-5(6)7(9)10/h1-4,8H,(H,9,10) checkY
    Key: YGSDEFSMJLZEOE-UHFFFAOYSA-N checkY
  • InChI=1/C7H6O3/c8-6-4-2-1-3-5(6)7(9)10/h1-4,8H,(H,9,10)
    Key: YGSDEFSMJLZEOE-UHFFFAOYAQ
  • O=C(O)c1ccccc1O
Properties
C7H6O3
Molar mass 138.122 g/mol
Appearance Colorless to white crystals
Odor Odorless
Density 1.443 g/cm3 (20 °C)[2]
Melting point 158.6 °C (317.5 °F; 431.8 K)
Boiling point 211 °C (412 °F; 484 K)
at 20 mmHg[2][3]
Sublimes at 76 °C[3]
  • 1.24 g/L (0 °C)
  • 2.48 g/L (25 °C)
  • 4.14 g/L (40 °C)
  • 17.41 g/L (75 °C)[3]
  • 77.79 g/L (100 °C)[4]
Solubility Soluble in
oil of turpentine, toluene
Solubility in benzene
  • 0.46 g/100 g (11.7 °C)
  • 0.775 g/100 g (25 °C)
  • 0.991 g/100 g (30.5 °C)
  • 2.38 g/100 g (49.4 °C)
  • 4.4 g/100 g (64.2 °C)[3][4]
Solubility in chloroform
  • 2.22 g/100 mL (25 °C)[4]
  • 2.31 g/100 mL (30.5 °C)[3]
Solubility in methanol
  • 40.67 g/100 g (−3 °C)
  • 62.48 g/100 g (21 °C)[3]
Solubility in olive oil 2.43 g/100 g (23 °C)[3]
Solubility in acetone 39.6 g/100 g (23 °C)[3]
log P 2.26
Vapor pressure 10.93 mPa[3]
Acidity (pKa)
  1. 2.97 (25 °C)[5]
  2. 13.82 (20 °C)[3]
UV-vis (λmax) 210 nm, 234 nm, 303 nm (4 mg/dL in ethanol)[3]
−72.23·10−6 cm3/mol
1.565 (20 °C)[2]
2.65 D
Thermochemistry
Std enthalpy of
formation
(ΔfH⦵298)
 −589.9 kJ/mol
Std enthalpy of
combustion
(ΔcH⦵298)
 -3.025 MJ/mol[6]
Pharmacology
A01AD05 (WHO) B01AC06 (WHO) D01AE12 (WHO) N02BA01 (WHO) S01BC08 (WHO)
Hazards
Occupational safety and health (OHS/OSH):
Eye hazards
 Severe irritation
Skin hazards
 Mild irritation
GHS labelling:[7]
GHS05: Corrosive GHS07: Exclamation mark
Danger
H302, H318
P280, P305+P351+P338
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
1
0
Flash point 157 °C (315 °F; 430 K)
closed cup[3]
540 °C (1,004 °F; 813 K)[3]
Lethal dose or concentration (LD, LC):
480 mg/kg (mice, oral)
Safety data sheet (SDS) MSDS[dead link]
Related compounds
Related compounds
Sulfosalicylic acid,
Salicylate synthase
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Salicylic acid is an organic compound with the formula HOC6H4COOH.[3] A colorless (or, white), bitter-tasting solid, it is a precursor to and a

willow tree, from which it was initially identified and derived. It is an ingredient in some anti-acne products. Salts and esters of salicylic acid are known as salicylates.[3]

Uses

Medicine

Main article: Medical uses of salicylic acid
Cotton pads soaked in salicylic acid can be used to chemically exfoliate skin.

Salicylic acid as a medication is commonly used to remove the outer layer of the

ringworm, dandruff, and ichthyosis.[3][10][11]

Similar to other hydroxy acids, salicylic acid is an ingredient in many

corns, keratosis pilaris, acanthosis nigricans, ichthyosis, and warts.[12]

Uses in manufacturing

Salicylic acid is used as a

food preservative, a bactericide, and an antiseptic.[13][14]

Salicylic acid is used in the production of other pharmaceuticals, including

4-aminosalicylic acid, sandulpiride, and landetimide (via salethamide).[15]

Salicylic acid has long been a key starting material for making

NSAIDs) are compared. In veterinary medicine, this group of drugs is mainly used for treatment of inflammatory musculoskeletal disorders.[17]

Pepto-Bismol and some formulations of Kaopectate
.

Other derivatives include

antitubercular agent often administered in association with isoniazid.[20]

vacuum ultraviolet spectral range, with nearly flat quantum efficiency for wavelengths between 10 and 100 nm.[21] It fluoresces in the blue at 420 nm. It is easily prepared on a clean surface by spraying a saturated solution of the salt in methanol followed by evaporation.[citation needed
]

Mechanism of action

Salicylic acid modulates

COX-1 enzymatic activity to decrease the formation of pro-inflammatory prostaglandins. Salicylate may competitively inhibit prostaglandin formation. Salicylate's antirheumatic (nonsteroidal anti-inflammatory) actions are a result of its analgesic and anti-inflammatory mechanisms.[citation needed
]

Salicylic acid, when applied to the skin surface, works by causing the cells of the epidermis to slough off more readily, preventing pores from clogging up, and allowing room for new cell growth. Salicylic acid inhibits the oxidation of uridine-5-diphosphoglucose (UDPG) competitively with NADH and noncompetitively with UDPG. It also competitively inhibits the transferring of glucuronyl group of uridine-5-phosphoglucuronic acid to the phenolic acceptor.[22]

The wound-healing retardation action of salicylates is probably due mainly to its inhibitory action on mucopolysaccharide synthesis.[5]

Safety

Main article: Salicylate poisoning

If high concentrations of salicylic ointment are used topically, high levels of salicylic acid can enter the blood, requiring hemodialysis to avoid further complications.[23]

Cosmetic applications of the drug pose no significant risk.[24] Even in a worst-case use scenario in which one was using multiple salicylic acid containing topical products, the aggregate plasma concentration of salicylic acid was well below what was permissible for acetylsalicylic acid (aspirin).[24] Since oral aspirin (which produces much higher salicylic acid plasma concentrations than dermal salicylic acid applications) poses no significant adverse pregnancy outcomes in terms of frequency of stillbirth, birth defects or developmental delay, use of salicylic acid containing cosmetics is safe for pregnant women.[24] Salicylic acid is present in most fruits and vegetables as for example in greatest quantities in berries and in beverages like tea.

Production and chemical reactions

Biosynthesis

Salicylic acid is biosynthesized from the amino acid phenylalanine. In Arabidopsis thaliana, it can be synthesized via a phenylalanine-independent pathway.

Chemical synthesis

Commercial vendors prepare

Kolbe-Schmitt reaction. Acidifying the product with sulfuric acid
gives salicylic acid:

At the laboratory scale, it can also be prepared by the hydrolysis of aspirin (acetylsalicylic acid)[25] or methyl salicylate (oil of wintergreen) with a strong acid or base; these reactions reverse those chemicals' commercial syntheses.

Reactions

Upon heating, salicylic acid converts to phenyl salicylate:[26][8]

2 HOC6H4CO2H → C6H5O2C6H4OH + CO2 + H2O

Further heating gives xanthone.[8]

Salicylic acid as its conjugate base is a chelating agent, with an affinity for iron(III).[27]

Salicylic acid slowly degrades to phenol and carbon dioxide at 200–230 °C:[28]

C6H4OH(CO2H) → C6H5OH + CO2

All isomers of

chlorination of salicylic acid.[8]

History

Main article: History of aspirin
White willow (Salix alba) is a natural source of salicylic acid.

Willow has long been used for medicinal purposes. Dioscorides, whose writings were highly influential for more than 1,500 years,[29] used 'Itea' (which was possibly a species of willow) as a treatment for 'painful intestinal obstructions,' birth control, for 'those who spit blood,' to remove calluses and corns and, externally, as a 'warm pack for gout.' William Turner, in 1597, repeated this, saying that willow bark, 'being burnt to ashes, and steeped in vinegar, takes away corns and other like risings in the feet and toes.'[30] Some of these cures may describe the action of salicylic acid, which can be derived from the salicin present in willow. It is, however, a modern myth that Hippocrates used willow as a painkiller.[31]

Hippocrates, Galen, Pliny the Elder, and others knew that decoctions containing salicylate could ease pain and reduce fevers.[32][33]

It was used in Europe and China to treat these conditions.[34] This remedy is mentioned in texts from Ancient Egypt, Sumer, and Assyria.[35]

The Cherokee and other Native Americans use an infusion of the bark for fever and other medicinal purposes.[36] In 2014, archaeologists identified traces of salicylic acid on seventh-century pottery fragments found in east-central Colorado.[37]

The

Chipping Norton, Oxfordshire, England, reported in 1763 that the bark of the willow was effective in reducing a fever.[38]

An extract of willow bark, called salicin, after the Latin name for the white willow (Salix alba), was isolated and named by German chemist Johann Andreas Buchner in 1828.[39] A larger amount of the substance was isolated in 1829 by Henri Leroux, a French pharmacist.[40] Raffaele Piria, an Italian chemist, was able to convert the substance into a sugar and a second component, which on oxidation becomes salicylic acid.[41][42] Salicylic acid was also isolated from the herb meadowsweet (

gastric irritation, bleeding, diarrhea
, and even death when consumed in high doses.

In 1874 the Scottish physician Thomas MacLagan experimented with salicin as a treatment for acute rheumatism, with considerable success, as he reported in The Lancet in 1876.[44] Meanwhile, German scientists tried sodium salicylate with less success and more severe side effects.[45][46]

In 1979, salicylates were found to be involved in induced defenses of

Sauromatum guttatum, to produce heat.[48]

Dietary sources

Salicylic acid occurs in plants as free salicylic acid and its carboxylated esters and phenolic glycosides. Several studies suggest that humans metabolize salicylic acid in measurable quantities from these plants.

nuts, and olive oil.[18] Meat, poultry, fish, eggs, dairy products, sugar, breads and cereals have low salicylate content.[18][50]

Some people with sensitivity to dietary salicylates may have symptoms of

gastrointestinal disorders, or diarrhea, so may need to adopt a low-salicylate diet.[18]

Plant hormone

Salicylic acid is a

salicylate hydroxylase. Pathogen inoculation did not produce the customarily high SA levels, SAR was not produced, and no PR genes were expressed in systemic leaves. Indeed, the subjects were more susceptible to virulent – and even normally avirulent – pathogens.[51]

Exogenously, salicylic acid can aid plant development via enhanced seed germination, bud flowering, and fruit ripening, though too high of a concentration of salicylic acid can negatively regulate these developmental processes.[54]

The volatile methyl ester of salicylic acid,

stomata of the nearby plant, where it can induce an immune response after being converted back to salicylic acid.[56]

Signal transduction

A number of proteins have been identified that interact with SA in plants, especially salicylic acid binding proteins (SABPs) and the NPR genes (nonexpressor of pathogenesis-related genes), which are putative receptors.[57]

See also

References

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  3. ^ a b c d e f g h i j k l m n o p q r s "Salicylic acid". PubChem, US National Library of Medicine. 19 Nov 2023. Retrieved 19 Nov 2023.
  4. ^ a b c Atherton Seidell, William F. Linke (1952). Solubilities of Inorganic and Organic Compounds: A Compilation of Solubility Data from the Periodical Literature. Supplement to the third edition containing data published during the years 1939-1949.
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  17. ^ "ACETYLSALICYLIC ACID, SODIUM ACETYLSALICYLATE, ACETYLSALICYLIC ACID DL-LYSINE AND CARBASALATE CALCIUM SUMMARY REPORT" (PDF). No. EMEA/MRL/695/99–FINAL. COMMITTEE FOR VETERINARY MEDICINAL PRODUCTS. The European Agency for the Evaluation of Medicinal Products Veterinary Medicines and Inspections. November 1999.
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  40. ^ See:
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  57. ^ Kumar, D. 2014. Salicylic acid signaling in disease resistance. Plant Science 228:127–134.

Further reading

External links

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