Salicylic acid

Structural formula
General
Surname	Salicylic acid
other names	2-hydroxybenzenecarboxylic acid ( IUPAC ) 2-hydroxybenzoic acid SALICYLIC ACID ( INCI ) ortho- hydroxybenzoic acid o -hydroxybenzoic acid Spiric acid Spiroylic acid
Molecular formula	C 7 H 6 O 3
Brief description	colorless, odorless, scratchy, sweet-sour tasting crystals with an unpleasant aftertaste
External identifiers / databases
CAS number 69-72-7 EC number 200-712-3 ECHA InfoCard 100,000,648 PubChem 338 ChemSpider 331 DrugBank DB00936 Wikidata Q193572
Drug information
ATC code	D01 AE12 S01 BC08
properties
Molar mass	138.12 g mol −1
Physical state	firmly
density	1.44 g cm −3
Melting point	159  ° C
boiling point	211 ° C (27 hPa )
pK s value	pK s COOH = 2.75 pK s OH = 12.38
solubility	good in ethanol (496 g l −1 at 15 ° C) bad in cold water (2 g l −1 at 20 ° C)
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS hazard labeling from  Regulation (EC) No. 1272/2008 (CLP) , expanded if necessary danger H and P phrases H: 302-318-361d P: 280-301 + 330 + 331-305 + 351 + 338-310
Toxicological data	400 mg kg −1 ( LD 50 ,  cat ,  oral ) 480 mg kg −1 ( LD 50 ,  mouse ,  oral ) 1300 mg kg −1 ( LD 50 ,  rabbit ,  oral ) 891 mg kg −1 ( LD 50 ,  rat ,  oral ) > 2000 mg kg −1 ( LD 50 ,  rat ,  transdermal ) 57 mg kg −1 ( TD Lo ,  male ,  transdermal ) 111 mg kg −1 ( TD Lo ,  woman ,  transdermal , 10 days)
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Salicylic acid ( o -hydroxybenzoic acid ) is a chemical substance with antipyretic and analgesic effects. Salicylic acid occurs in the form of its methyl ester in essential oils and as a plant hormone in the leaves , flowers and roots of various plants and is important for the plant's defense against pathogens . It got its name because it used to be obtained mainly through the oxidative processing of salicin , which is contained in the bark of various willows (scientifically Salix spec. ).

It is also known under the name of spiric acid because it can be obtained from the juice of the sparrow bush ( meadowsweet ). From the name Spirsäure also the brand name derives aspirin for acetylsalicylic acid from: A cetyl spir acid. The salts of salicylic acid are called salicylates .

Raffaele Piria first isolated salicylic acid from salicin (1838).

Occurrence and extraction

biosynthesis

Salicylic acid is found in a variety of plants and acts there as a phytohormone . There are two compartmentalized routes of biosynthesis: the phenylpropanoid route in the cytoplasm starting from phenylalanine and the isochorismate route in the chloroplasts. Most salicylic acid is methylated as liquid methyl salicylate in order to be effective as a volatile derivative for long-distance transport. In tobacco plants and Arabidopsis thaliana it was shown that this form is important for systemically acquired resistance. In addition, the salicylic acid can be glycosylated and stored as an inactive form in the vacuoles.

Technical manufacturing

Technically, it is produced from carbon dioxide and sodium phenolate using the Kolbe-Schmitt reaction (also referred to simply as salicylic acid synthesis) . This artificial production has largely replaced the extraction from willow bark.

As early as 1874, based on an idea by Hermann Kolbe , the synthesis of salicylic acid was transferred from the laboratory to factory production, with the Schmitt student Friedrich von Heyden running the salicylic acid factory Dr. F. von Heyden in Dresden, which moved to Radebeul a year later . From there, salicylic acid was marketed as the world's first industrially produced and “packaged” drug. Friedrich von Heyden is considered to be the founder of industrial salicylic acid production in the pharmaceutical industry.

Chemical-physical properties

Salicylic acid crystals

Salicylic acid is one of the aromatics due to the benzene ring it contains . Since it contains a carboxy and a hydroxyl group , it belongs to the hydroxycarboxylic acids . Because of the β-stability of the carboxy to the hydroxyl group, it can also be referred to as β-hydroxycarboxylic acid. Since the hydroxyl group is bound directly to the aromatic benzene ring, it also belongs to the phenols and thus also to the phenolic acids .

On rapid, intense heating, salicylic acid decarboxylates to form phenol . Above 76 ° C, the substance partially sublimes , and the cooling vapors form needle-shaped crystals .

The  high acidity - compared to other hydroxybenzoic acids - is due to the stabilization of the salicylate anion through a hydrogen bond with the neighboring hydroxy group.

Analytical evidence: Since salicylic acid is formally the enol (in this case a phenol ) of a β-ketocarboxylic acid, it forms a purple-colored complex with iron (III) chloride solution, the tris-salicylate iron (III) complex:

This detection is not specific as compounds similar to acetoacetic esters have the same reaction. The flash point is 157 ° C and the ignition temperature is 570 ° C.

Biological function

As a phytohormone, salicylic acid plays an important role as a regulatory signal in the event of abiotic stress such as dryness and heat, cold or osmotic pressure. In addition, it is important for the plant in defense against pathogens, is expressed both locally and systemically in the event of an attack, and is able to modulate gene expression. There is also evidence that salicylic acid plays a role in the growth and development of the plant.

use

"Salicylic ointment" of the German Red Cross from the 1930s

Salicylic acid is used in the production of dyes and fragrances and acetylsalicylic acid (ASA, also known under the brand name aspirin ), which is used as a pain reliever, anti-inflammatory and anti-coagulant drug . In the form of the insoluble salt bismuth subsalicylate , it is used against diarrhea and disorders of the gastrointestinal tract.

Furthermore, salicylic acid is used as a flux in soft soldering .

Salicylic acid has an antimicrobial effect, but its use as a preservative in food is prohibited. In cosmetics, salicylic acid is approved in accordance with Regulation (EC) No. 1223/2009 on cosmetic agents as an anti-dandruff agent in hair washing agents up to a maximum of 3%, for other agents up to a concentration of 2% and when used as a preservative up to a maximum of 0.5% . In medicinal products , salicylic acid from 5% solution shows a kerato - and thus also comedolytic effect which is sufficient for acne therapy . In a 10% solution it is used to treat corns , warts and skin fungi .

unwanted effects

Side effects of pharmacotherapy

Salicylic acid is a metabolite of acetylsalicylic acid, which is rapidly hydrolyzed in the body . Side effects are mainly allergic reactions , a tendency to bleed, bronchoconstriction ( bronchial asthma ), gastric mucosal damage with bleeding, in individual cases liver damage. Uric acid retention, hyperuricemia, and kidney damage were also observed. An important metabolic pathway in the liver is conversion into salicyluric acid .

toxicity

On the skin, mucous membranes and eyes, salicylic acid is acutely irritating to tissue damaging. Furthermore, when taken orally or otherwise, the acid causes a dampening of the respiratory center and a disruption of important metabolic processes and the central nervous system . With chronic exposure, disorders of the gastrointestinal tract appear. In animal experiments, oral and dermal administration of salicylic acid showed a wide variety of effects on animals (cats, mice, rabbits and rats) such as drowsiness, muscle weakness and organ damage to the liver and kidneys. The acute toxicity LD ₅₀ was orally between 400 and 1300 mg / kg, dermally in rats at 2 g / kg. In humans, TD _Lo values ​​of 57 to 111 mg / kg were determined after dermal administration . The plasma half-life of salicylic acid is approximately 2-3 hours.

safety instructions

At the suggestion of Novacyl, the chemical classification of salicylic acid was revised in 2015 and 2016. The Committee for Risk Assessment (RAC) of the European Chemicals Agency (ECHA) changed the classification for salicylic acid as follows on March 10, 2016: Salicylic acid is classified as reproductive toxic Repr 2 as well as Acut Tox 4 and Eye Dam 1. The warnings have been set to H361d, H302 and H318. This classification of the RAC still has to be implemented by the EU Commission into applicable law, but with the publication it represents the state of knowledge that must be taken into account by companies and authorities.

Salicylic acid derivatives

Salts

Salicylic acid reacts with caustic soda to form sodium salicylate .

Ester

If salicylic acid reacts with an alcohol , a carboxylic acid ester or a salicylic acid ester is formed with elimination of water . It can also form esters with organic acids , in which case it then functions as an alcohol in the reaction. Salicylic acid esters are mainly used in the cosmetics and perfume industry as anti-rheumatic agents in bath additives, ointments or creams, as well as fragrances and UV filters in sunscreens. The best-known ester of salicylic acid is acetylsalicylic acid . Here the hydroxyl group of salicylic acid has been esterified with the carboxy group of acetic acid. Other relevant salicylic acid esters are methyl salicylate , ethyl salicylate , benzyl salicylate , isobutyl salicylate , isopentyl salicylate , phenyl salicylate and hydroxyethyl salicylate .

Halogen derivatives

By bromination with elemental bromine in glacial acetic acid , 3,5-dibromosalicylic acid is produced , the copper salt of which is used as a fungicide and bactericide .

The biochemically relevant 3,5-diiodosalicylic acid is obtained by iodination with iodine chloride . Salicylic acid derivatives halogenated at the 4-position, such as 4-iodosalicylic acid, cannot be obtained directly.

literature

• F. von Heyden: Salicylic acid . In: The Gazebo . Issue 10, 1863, pp. 172 ( full text [ Wikisource ]).
• Beilstein's manual . Volume 10, Textarchiv - Internet Archive (on salicylic acid and its derivatives, literature recorded up to 1910).

Web links

Wiktionary: Salicylic acid  - explanations of meanings, word origins, synonyms, translations

Individual evidence

1. ↑ entry to Salicylic Acid in CosIng database of the European Commission, accessed on 14 January 2020th
2. ↑ Entry on salicylic acid. In: Römpp Online . Georg Thieme Verlag, accessed on June 1, 2014.
3. ↑ ^{a b c d e f g h i} Entry on salicylic acid in the GESTIS substance database of the IFA , accessed on January 14, 2020(JavaScript required) .
4. ↑ ^{a b} CRC Handbook of Tables for Organic Compound Identification . Third Edition, 1984, ISBN 0-8493-0303-6 .
5. ↑ Claudia Synowietz, Klaus Schäfer (Ed.): Chemist Calendar. 3. Edition. Springer, Berlin / Heidelberg / New York / Tokyo 1984, ISBN 3-540-12652-X .
6. ↑ Entry on Salicylic acid in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on December 30, 2019. Manufacturers or distributors can expand the harmonized classification and labeling .
7. ↑ ^{a b c} Handbook of Toxicology. 4 volumes, WB Saunders Co., Philadelphia 1956-1959; Volume 5, 1959, p. 148.
8. ↑ ^{a b} Drugs in Japan. Volume 6, 1982, p. 291.
9. ↑ ^{a b} BIOFAX. Industrial Bio-Test Laboratories Inc., Data Sheets. Volume 21-3 / 1971.
10. ↑ ^{a b} Acute Toxicity Data. Journal of the American College of Toxicology, Part B. Volume 15 (Suppl.)
11. ↑ ^{a b} P. A. Soyka, LF Soyka: Absorption of salicylic acid . In: Journal of the American Medical Association . tape 244 , no. 7 , 1980, pp. 660-661 , PMID 7392165 (English, pmj.bmj.com [PDF]).
12. ^ ^{A b} C. M. Dwyer, RH McCloskey, RE Kerr: Poisoning from topical salicylic acid. In: Postgraduate Medical Journal . tape 70 , no. 820 , 1994, pp. 146 , PMID 8170891 , PMC 2397637 (free full text).
13. ^ Doris Schwarzmann-Schafhauser: Salicylic acid. In: Werner E. Gerabek u. a. (Ed.): Encyclopedia of medical history. De Gruyter, Berlin / New York 2005, ISBN 3-11-015714-4 , p. 1282.
14. ↑ For example Salix alba , Filipendula (Spirea) ulmaria and tea berries (Gautheria procumbens).
15. ↑ ^{a b} M. Rivas-San Vicente, J. Plasencia: Salicylic acid beyond defense: its role in plant growth and development . In: Journal of Experimental Botany . tape 62 , no. 10 , June 1, 2011, p. 3321-3338 , doi : 10.1093 / jxb / err031 .
16. ↑ Patent specification (German Patent DE4415527) on the use of salicylic acid or acetylsalicylic acid in soft soldering.
17. ^ AA Hartmann: The influence of various factors on the human resident skin flora . In: Seminars in Dermatology . tape 9 , no. 4 , 1990, pp. 305-308 , PMID 2285575 .
18. ↑ Salicylic acid as a preservative for consumer articles. Their worth, utility and harmlessness, justified by the judgment of competent authorities and judicial knowledge. Chemical factory von Heyden, Radebeul-Dresden 1896 urn : nbn: de: hbz: 061: 2-11219 .
19. ↑ Doris Fanta, Christine Messeritsch-Fanta: Acne 1999. Do we still need a dermatologist? In: The dermatologist . tape 50 , no. December 12 , 1999, pp. 900-911 , doi : 10.1007 / s001050051009 .
20. ↑ AW Frahm, HHJ Hager, F. v. Bruchhausen, M. Albinus, H. Hager: Hager's Handbook of Pharmaceutical Practice: Volume 4: Substances AK. Birkhäuser, 1999, ISBN 978-3-540-52688-9 , p. 42.
21. ↑ Specialist information Aspirin® 100 mg tablets (PDF) ( Memento of April 29, 2006 in the Internet Archive ).
22. ^ RAC decision of March 10, 2016
23. ↑ US Patent 399034: Biocidal 3,5-dibromosalicylic acid salts .

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !