Resorcinol

Structural formula
General
Surname	Resorcinol
other names	1,3-dihydroxybenzene m -dihydroxybenzene Resorcinol
Molecular formula	C 6 H 6 O 2
Brief description	large, colorless, sweet-tasting needles
External identifiers / databases
CAS number 108-46-3 EC number 203-585-2 ECHA InfoCard 100.003.260 PubChem 5054 ChemSpider 4878 DrugBank DB11085 Wikidata Q408865
Drug information
ATC code	D10 AX02
properties
Molar mass	110.11 g mol −1
Physical state	firmly
density	1.28 g cm −3
Melting point	110.7 ° C
boiling point	277 ° C
Vapor pressure	1 Pa (20 ° C)
pK s value	pK s 1 = 9.48 pK s 2 = 12.08
solubility	very good in water (1400 g l −1 at 20 ° C), ethanol , diethyl ether and glycerine bad in chloroform and carbon disulfide
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 Caution H and P phrases H: 302-315-319-400 P: 273-302 + 352-305 + 351 + 338
MAK	not yet classified Switzerland: 10 ml m −3
Toxicological data	301 mg kg −1 ( LD 50 ,  rat ,  oral ) 3360 mg kg −1 ( LD 50 ,  rabbit ,  transdermal )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Resorcinol (1,3-dihydroxybenzene, 1,3-benzenediol) is formally derived from benzene . The benzene nucleus has two hydroxyl groups in the meta position. It belongs to the group of phenols (diphenols) and is isomeric to catechol (1,2-dihydroxybenzene) and hydroquinone (1,4-dihydroxybenzene).

Extraction and presentation

Resorcinol may be obtained by distillation of natural resins (Latin resina win).

Technically, it is produced by melting m -benzenesulfonic acid with sodium hydroxide (alkali melt). It is noticeable sodium sulfite as a by-product.

Today, the alkali melt process is obsolete because of the high salt loads associated with it and has been replaced in industrial practice by the cumene hydroperoxide process developed by Heinrich Hock and adapted by the Japanese companies Sumitomo Chemical and Mitsui Chemicals . In this case, 1,3-diisopropylbenzene in the liquid phase at temperatures of 80 to 100 ° C with atmospheric oxygen to give 1,3-diisopropylbenzene dihydroperoxide (m-DHP) was oxidized and, after removal of by-products in the homogeneous phase with sulfuric acid or heterogeneous acidic alumino-silicates with practically quantitative yields rearranged to resorcinol and acetone .

properties

Resorcinol on a ceramic bowl: colorless to pale gray-pink crystals

Physical Properties

Resorcinol easily dissolves in water, ethanol and ether. At 20 ° C, 1400 grams of resorcinol dissolve in 1 liter of water. The good solubility in water is mainly caused by hydrogen bonds between the two phenolic hydroxyl groups and the solvent molecules .

Chemical properties

Resorcinol enters into a color reaction characteristic of phenols with iron (III) chloride solution; a deep purple solution forms.

Like all phenols, resorcinol has a weakly acidic effect, since the phenolic hydroxyl groups are more easily deprotonated than alcoholic ones; The acidity constant for the first protolysis stage is pK _s  = 9.48.

In contrast to catechol and hydroquinone, resorcinol has only a weak reducing effect and no elemental silver precipitates from ammoniacal silver nitrate solution . Only in the heat does black silver deposit.

Even an alkaline solution turns yellow only very slowly in air. Alkaline solutions of catechol and hydroquinone, on the other hand, quickly turn brown when exposed to oxygen .

Resorcinol can also be used to differentiate between fructose and glucose . If you mix fructose, resorcinol and concentrated hydrochloric acid together, the result is a striking red color ( Seliwanow sample ). This proof is extremely helpful, since fructose, as ketohexose , provides a positive Fehling test , due to the easy conversion of fructose to glucose, or also forms semi-acetal OH groups.

Reactions

Sodium amalgam reduces the resorcinol to dihydroresorcinol ( 1,3-cyclohexanedione ), which is converted into 4-acetylbutyric acid ( 5-oxohexanoic acid , CAS number: 3128-06-1) when heated to 150–160 ° C with a concentrated barium hydroxide solution .

2,4,6-tribromoresorcinol is formed with bromine water . If bromine is used in excess, the 2,4,6-tribromoresorcinol reacts further to form 2,4,4,6,6-pentabromo-1-cyclohexene-3,5-dione. This reaction can be reversed by adding potassium iodide .

Acylation takes place with acids and acid chlorides in the presence of dehydrating agents , so the reaction with glacial acetic acid with zinc chloride as a catalyst at 145 ° C produces resacetophenone .

With the anhydrides of dibasic acids fluoresceins are formed, e.g. B. Phthalic anhydride produces fluorescein :

A water-soluble, blue substance forms with sodium nitrite , which turns red when acid is added. This substance is called lacmoid or resorcinol blue and is used as an indicator .

Resorcinol condenses with aldehydes , so methylenediresorcinol is formed with formaldehyde in the presence of hydrochloric acid as a catalyst. With chloral hydrate in the presence of potassium bisulfate as a catalyst, the lactone of tetraoxydiphenylmethane carboxylic acid is formed.

In an alcoholic solution, resorcinol condenses with sodium acetylacetate to form methylumbelliferone.

Trinitroresorcinol ( styphnic acid ) is formed when reacting with concentrated nitric acid and cold concentrated sulfuric acid . Styphnic acid and especially its lead salt are used as explosives.

2,4-Dihydroxybenzoic acid can be produced in a Kolbe-Schmitt reaction by carboxylation with potassium hydrogen carbonate .

Resorcinol can condense with aldehydes under Brønstedt acid catalysis to resorcinarenes .

Metabolism and toxicity

In studies, resorcinol mainly forms glucoroid conjugates in rats. In general, like other dihydroxybenzenes, resorcinol is also considered to be more toxic than phenol. Compared to other dihydroxybenzenes, however, it is considered to be less toxic.

use

Resorcinol is used in the production of dyes , especially triphenylmethane dyes ( fluorescein , eosin Y ), and plastics ( phenoplasts ). The main use of resorcinol and resorcinol resins is to promote adhesion between fabric inserts or steel cord and rubber compounds in tire construction (RFL dip). Resorcinol -formaldehyde resins ( phenol-resorcinol-formaldehyde glue ) are used as an adhesive in the manufacture of plywood and other wood constructions. More recent applications are flame retardants based on phosphoric acid esters and light-resistant, transparent polymers .

Pharmacological effect

Resorcinol is poisonous in high doses; in diluted solutions it has an antiseptic effect and is therefore used in dermatology to heal eczema in ointments or hair lotions , as well as a keratolytic in dermatoses of the hairy scalp.

Taking too high doses of resorcinol leads to severe symptoms of intoxication such as hypothermia , hypotension , difficulty breathing and, in children, hemoglobinuria . Even after use in the ointments described above, it can lead to intoxication. In rare cases, resorcinol causes skin irritation or even contact dermatitis.

In animal studies on rats mg / kg body weight was affected at a dose of 260 a day increased mortality. At lower doses, studies showed no increased mortality among rats even over a longer observation period.

Hazard assessment

Resorcinol was included by the EU in 2012 in accordance with Regulation (EC) No. 1907/2006 (REACH) in the context of substance evaluation in the Community's ongoing action plan ( CoRAP ). The effects of the substance on human health and the environment are re-evaluated and, if necessary, follow-up measures are initiated. Resorcinol inclusion was driven by concerns about consumer use , high (aggregated) tonnage and widespread use, and as a potential endocrine disruptor . The reassessment started in 2016 and was carried out by Finland . A final report was then published.

In 2019 resorcinol was again added to the CoRAP list. This continued to be caused by concerns about high (aggregated) tonnage and a potential endocrine disruptor . The re-evaluation has been running since 2019 and is carried out by France .

Web links

Commons : Resorcinol  - collection of images, videos and audio files

Individual evidence

1. ↑ ^{a b c} Entry on resorcinol. In: Römpp Online . Georg Thieme Verlag, accessed on March 3, 2014.
2. ↑ ^{a b c d e f g h i j} Entry on resorcinol in the GESTIS substance database of the IFA , accessed on January 8, 2020(JavaScript required) .
3. ↑ ^{a b c} CRC Handbook of Tables for Organic Compound Identification , Third Edition, 1984, ISBN 0-8493-0303-6 .
4. ↑ Entry on resorcinol in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .
5. ↑ Swiss Accident Insurance Fund (Suva): Limit values ​​- current MAK and BAT values (search for 108-46-3 or resorcinol ), accessed on November 2, 2015.
6. ↑ Hans-Jürgen Arpe: Industrial Organic Chemistry: Important preliminary and intermediate products, 6th edition. Wiley-VCH Verlag, Weinheim 2007, ISBN 978-3-527-31540-6 , p. 404-405 .
7. ↑ Patent US3923908 : Process for the preparation of hydroquinone and / or resorcinol by the cleavage of dihydroperoxides. Filed on October 31, 1973 , published on December 2, 1975 , Applicant: Sumitomo Chemical Co., Ltd., Inventor: H. Suda et al
8. ↑ Patent US4229597 : Process for the preparation of resorcinol. Applied on October 3, 1978 , published October 21, 1980 , Applicant: Mitsui Petrochemical Industries, Ltd., Inventor: T. Taguchi, T. Ago, I. Hashimoto. ‌
9. ↑ G. Merling: About Dihydroresorcinol . In: Justus Liebig's Annals of Chemistry . tape 278 , no. 1 , January 1894, p. 20-57 , doi : 10.1002 / jlac.18942780103 .
10. ↑ Ralf Krelaus: Synthesis of bicyclic lactams by Ugi reaction and ring-closing metathesis . Paderborn 2003, DNB  968549772 , urn : nbn: de: hbz: 466-20030101177 (dissertation, University of Paderborn).
11. ↑ Timo Liebig: Concave N-heterocyclic catalyst systems . Kiel 2006, DNB  980883172 , urn : nbn: de: gbv: 8-diss-17594 (dissertation, University of Kiel).
12. ↑ Michael Abbass: Concave 1,10-phenanthrolines with additional functionality in the 4'-position . Kiel 2002, DNB  971656959 , urn : nbn: de: gbv: 8-diss-5710 (dissertation, University of Kiel).
13. ↑ HP Latscha, HA Klein, GW Linti: Analytical Chemistry ( limited preview in the Google book search).
14. ↑ M. Nencki, N. Sieber: About the compounds of mono- and dibasic fatty acids with phenols . In: Journal for Practical Chemistry . tape 23 , no. 1 , 1880, p. 147–156 ( digitized on Gallica ).
15. ↑ Working instructions on www.oc-praktikum.de (PDF; 117 kB).
16. ↑ Reaction mechanism for the formation of fluorescein ( Memento from April 15, 2010 in the Internet Archive ) ( MS Word ; 52 kB).
17. ↑ MC Traub, C. Hock: About a Lakmoid . In: Reports of the German Chemical Society . tape 17 , no. 2 , July 1884, p. 2615-2617 , doi : 10.1002 / cber.188401702192 .
18. ^ JT Hewitt, FG Pope The condensation of chloral with resorcinol . In: Journal of the Chemical Society, Transactions . No. 75, 1897, pp. 1084-1090, doi: 10.1039 / CT8977101084 .
19. ↑ Arthur Michael: About the behavior of sodium malonic ether against resorcinol . In: Journal for Practical Chemistry . tape 37 , no. 1 , 1888, p. 469-471 ( digitized on Gallica ).
20. ↑ M. Kidney Stone, DA Clibbens: β-Resorcylic Acid In: Organic Syntheses . 10, 1930, p. 94, doi : 10.15227 / orgsyn.010.0094 ; Coll. Vol. 2, 1943, p. 557 ( PDF ).
21. ↑ PC Merker, D. Yeung, D. Doughty, S. Nacht: Pharmacokinetics of resorcinol in the rat . In: Research Communications in Chemical Pathology and Pharmacology . tape 38 , no. 3 , December 1982, ISSN  0034-5164 , pp. 367-388 , PMID 7163635 .
22. ↑ S. Suresh, Vimal Chandra Srivastava, Indra Mani Mishra: Study of Catechol and Resorcinol Adsorption Mechanism through Granular Activated Carbon Characterization, pH and Kinetic Study . In: Separation Science and Technology . tape 46 , no. 11 , July 1, 2011, ISSN  0149-6395 , p. 1750–1766 , doi : 10.1080 / 01496395.2011.570284 .
23. ↑ Kroschwitz, Jacqueline I., Seidel, Arza: Kirk-Othmer encyclopedia of chemical technology. 5th ed. No. 11 . Hoboken, NJ, ISBN 978-0-471-48494-3 , pp. 462 .
24. ^ World Health Organization Staff, International Agency for Research on Cancer (IARC): Some Fumigants, the Herbicides 2, 4-D and 2, 4, 5-T, Chlorinated Dibenzodioxins and Miscellaneous Industrial Chemicals. World Health Organization, Geneva 1977, ISBN 92-832-1215-0 .
25. ↑ International Agency for Research on Cancer: Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide. World Health Organization, International Agency for Research on Cancer, [Lyon, France] 1999, ISBN 978-92-832-1271-3 .
26. ↑ J. Vilaplana, C. Romaguera, F. Grimalt: Contact dermatitis from resorcinol in a hair dye . In: Contact Dermatitis . tape 24 , no. 2 , February 1991, p. 151–152 , doi : 10.1111 / j.1600-0536.1991.tb01682.x .
27. ↑ Luigi Massone, Antonio Anonide, Susanna Borghi, David Usiglio: Contact dermatitis of the eyelids from resorcinol in an ophthalmic ointment . In: Contact Dermatitis . tape 29 , no. 1 , July 1993, p. 49-49 , doi : 10.1111 / j.1600-0536.1993.tb04545.x .
28. ↑ National Toxicology Program: Toxicology and Carcinogenesis Studies of Resorcinol (CAS No. 108-46-3) in F344 Rats and B6C3F1 Mice (Gavage Studies) . In: National Toxicology Program Technical Report Series . tape 403 , July 1992, ISSN  0888-8051 , p. 1-234 , PMID 12621515 .
29. ↑ European Chemicals Agency (ECHA): Substance Evaluation Conclusion and Evaluation Report .
30. ↑ ^{a b} Community rolling action plan ( CoRAP ) of the European Chemicals Agency (ECHA): Resorcinol , accessed on March 26, 2019.