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Resorcinol
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Resorcinol
Skeletal formula
Skeletal formula
Ball-and-stick model
Ball-and-stick model
Names
Preferred IUPAC name
Benzene-1,3-diol[1]
Other names
Resorcinol[1]
Resorcin
m-Dihydroxybenzene
1,3-Benzenediol
1,3-Dihydroxybenzene
3-Hydroxyphenol
m-Benzenediol
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.003.260 Edit this at Wikidata
KEGG
UNII
UN number 2876
  • InChI=1S/C6H6O2/c7-5-2-1-3-6(8)4-5/h1-4,7-8H checkY
    Key: GHMLBKRAJCXXBS-UHFFFAOYSA-N checkY
  • InChI=1/C6H6O2/c7-5-2-1-3-6(8)4-5/h1-4,7-8H
    Key: GHMLBKRAJCXXBS-UHFFFAOYAB
  • c1cc(cc(c1)O)O
Properties
C6H6O2
Molar mass 110.111 g/mol
Appearance White solid[2]
Odor Faint[2]
Density 1.28 g/cm3, solid
Melting point 110 °C (230 °F; 383 K)
Boiling point 277 °C (531 °F; 550 K)
110 g/100 mL at 20 °C
Vapor pressure 0.0002 mmHg (25 °C)[2]
Acidity (pKa) 9.15[3]
−67.26×10−6 cm3/mol
1.578[4]
2.07±0.02 D[5]
Thermochemistry
−368.0 kJ·mol−1[4]
Enthalpy of fusion (ΔfH⦵fus)
 20.4 kJ·mol−1[4]
Pharmacology
D10AX02 (WHO) S01AX06 (WHO)
Hazards
GHS labelling:
GHS05: CorrosiveGHS07: Exclamation markGHS09: Environmental hazard
H302, H313, H315, H318, H400
P273, P280, P305+P351+P338
Flash point 127 °C; 261 °F; 400 K[2]
608 °C (1,126 °F; 881 K)[4]
Explosive limits 1.4%-?[2]
NIOSH (US health exposure limits):
PEL (Permissible)
 none[2]
REL (Recommended)
 TWA 10 ppm (45 mg/m3) ST 20 ppm (90 mg/m3)[2]
IDLH (Immediate danger)
 N.D.[2]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Resorcinol (or resorcin) is a phenolic compound. It is an organic compound with the formula C6H4(OH)2. It is one of three isomeric benzenediols, the 1,3-isomer (or meta-isomer). Resorcinol crystallizes from benzene as colorless needles that are readily soluble in water, alcohol, and ether, but insoluble in chloroform and carbon disulfide.[6]

Production

[edit]

Resorcinol is produced in several steps from benzene, starting with dialkylation with propylene to give 1,3-diisopropylbenzene. Oxidation and Hock rearrangement of this disubstituted arene gives acetone and resorcinol.[6]

Production of resorcinol via Hock Rearrangement

Resorcinol is a relatively inexpensive chemical.[7] It is produced in only a very few locations around the world (as of 2010 only four commercial plants were known to be operative: in the United States, Germany, China, and Japan), and is the determining factor in the cost of PRF adhesives.[8] Production in the United States ended in 2017 with the closure of Indspec Chemical's plant in Petrolia, Pennsylvania.[9]

Many additional routes exist for resorcinol. It was formerly produced by disulfonation of benzene followed by hydrolysis of the 1,3-disulfonate. This method has been discarded because it cogenerates so much sulfur-containing waste. Resorcinol can also be produced when any of a large number of resins (such as galbanum and asafoetida) are melted with potassium hydroxide, or by the distillation of Brazilwood extract. It may be synthesized by melting 3-iodophenol, phenol-3-sulfonic acid with potassium carbonate. Diazotization of 3-aminophenol or on 1,3-diaminobenzene followed by hydrolysis provides yet another route.[10] Many ortho- and para-compounds of the aromatic series (for example, the bromophenols, benzene-para-disulfonic acid) also yield resorcinol on fusion with potassium hydroxide.

Reactions

[edit]

Partial hydrogenation of resorcinol gives dihydroresorcinol, also known as 1,3-cyclohexanedione.[11][12]

It reduces Fehling's solution and ammoniacal silver solutions. It does not form a precipitate with lead acetate solution, as does the isomeric pyrocatechol. Iron(III) chloride colors its aqueous solution a dark-violet, and bromine water precipitates tribromoresorcinol. These properties are what give it its use as a colouring agent for certain chromatography experiments.

Sodium amalgam reduces it to dihydroresorcin, which when heated to 150 to 160 °C with concentrated barium hydroxide solution gives γ-acetylbutyric acid.[citation needed]

When fused with potassium hydroxide, resorcinol yields phloroglucin, pyrocatechol, and diresorcinol. It condenses with acids or acid chlorides, in the presence of dehydrating agents, to oxyketones, for example, with zinc chloride and glacial acetic acid at 145 °C it yields resacetophenone (HO)2C6H3COCH3.[13] With the anhydrides of dibasic acids, it yields fluoresceins. When heated with calcium chloride—ammonia to 200 °C it yields meta-dioxydiphenylamine.[14]

With sodium nitrite it forms a water-soluble blue dye, which is turned red by acids, and is used as a pH indicator under the name of lacmoid.[15] It condenses readily with aldehydes, yielding with formaldehyde, on the addition of catalytic hydrochloric acid, methylene diresorcin [(HO)C6H3(O)]2CH2. Reaction with chloral hydrate in the presence of potassium bisulfate yields the lactone of tetra-oxydiphenyl methane carboxylic acid.[16] In alcoholic solution it condenses with sodium acetoacetate to form 4-methylumbelliferone.[17]

In addition to electrophilic aromatic addition, resorcinol (and other polyols) undergo nucleophilic substitution via the enone tautomer.

Nitration with concentrated nitric acid in the presence of cold concentrated sulfuric acid yields trinitroresorcin (styphnic acid), an explosive.

Occurrence and use

[edit]

Derivatives of resorcinol are found in different natural sources. Alkylresorcinols are found in rye.[18] Polyresorcinols are found as pseudotannins in plants.[19]

Adhesives

[edit]
Main article: Resorcinol glue

Resorcinol is mainly used in the production of resins. As a mixture with phenol, it condenses with formaldehyde to afford adhesives. Such resins are used as adhesives in the rubber industry and others are used for wood glue.[6] In relation to its conversion resins with formaldehyde, resorcinol is the starting material for resorcinarene rings.

Medical uses

[edit]

It is present in over-the-counter topical acne treatments at 2% or less concentration, and in prescription treatments at higher concentrations.[20] Monoacetylresorcinol, C6H4(OH)(O–COCH3), is used under the name of Euresol.[21] It is used in hidradenitis suppurativa with limited evidence showing it can help with resolution of the lesions.[22] Resorcinol is one of the active ingredients in products such as Resinol, Vagisil, and Clearasil.

In the 1950s and early 1960s the British Army used it, in the form of a paste applied directly to the skin. One such place where this treatment was given to soldiers with chronic acne was the Cambridge Military Hospital, Aldershot, England. It was not always successful.

A resorcinol derivative, 4-hexylresorcinol, is an anesthetic found in throat lozenges.

Chemical uses

[edit]

Resorcinol is used as a chemical intermediate for the synthesis of pharmaceuticals and other organic compounds. It is used in the production of diazo dyes and plasticizers and as a UV absorber in resins.

It is an analytical reagent for the qualitative determination of ketoses (Seliwanoff's test).

It is the starting material for the initiating explosive lead styphnate.[23]

[edit]

Resazurin, C12H7NO4, obtained by the action of nitrous acid on resorcinol,[24] forms small dark red crystals possessing a greenish metallic glance. When dissolved in concentrated sulfuric acid and warmed to 210 °C, the solution on pouring into water yields a precipitate of resorufin, C12H7NO3, an oxyphenoxazone, which is insoluble in water but is readily soluble in hot concentrated hydrochloric acid, and in solutions of caustic alkalis. The alkaline solutions are of a rose-red color and show a cinnabar-red fluorescence. A tetrabromresorufin is used as a dyestuff under the name of Fluorescent Resorcin Blue.

Thioresorcinol is obtained by the action of zinc and hydrochloric acid on meta-benzenedisulfonyl chloride. It melts at 27 °C and boils at 243 °C. Resorcinol disulfonic acid, (HO)2C6H2(HSO3)2, is a deliquescent mass obtained by the action of sulfuric acid on resorcin.[25] It is readily soluble in water and ethanol.

Resorcinol is also a common scaffold that is found in a class of anticancer agents, some of which (luminespib, ganetespib, KW-2478, and onalespib) were in clinical trials as of 2014.[26][27] Part of the resorcinol structure binds to inhibits the N-terminal domain of heat shock protein 90, which is a drug target for anticancer treatments.[26]

History, etymology, and nomenclature

[edit]

Austrian chemist Heinrich Hlasiwetz (1825–1875) is remembered for his chemical analysis of resorcinol and for his part in the first preparation of resorcinol, along with Ludwig Barth, which was published in 1864.[28]: 10 [29]

Benzene-1,3-diol is the name recommended by the International Union of Pure and Applied Chemistry (IUPAC) in its 1993 Recommendations for the Nomenclature of Organic Chemistry.[30]

Resorcinol is so named because of its derivation from ammoniated resin gum, and for its relation to the chemical orcinol.[31]

Toxicity

[edit]

Resorcinol has low toxicity, with an LD50 (rats, oral) > 300 mg/kg. It is less toxic than phenol.[6]

Resorcinol was named a substance of very high concern under European Union REACH in 2022 because of its endocrine disrupting properties.[32]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Resorcinol

View on Grokipedia
from Grokipedia
Resorcinol, also known as 1,3-benzenediol or meta-dihydroxybenzene, is an with the molecular formula C₆H₆O₂ and the structure of a ring with hydroxyl groups at the 1 and 3 positions. It exists as a white to light gray crystalline solid at , with a of 110–111 °C and high in , , and . First isolated in the from natural sources like resin, resorcinol is now primarily produced industrially through the sulfonation of to form benzenedisulfonic acid, followed by fusion with . Resorcinol serves as a key intermediate in the manufacture of numerous products, including phenolic resins, adhesives for wood and rubber (such as tire cord bonding), and UV stabilizers for polymers. In pharmaceuticals and , it functions as an , keratolytic agent for treating , eczema, and by promoting exfoliation of hardened skin, and as a component in hair dyes and topical treatments. Its role in dye production, particularly diazo dyes, and as a in underscores its versatility in industrial chemistry. Despite its utility, resorcinol exhibits notable , causing and eye irritation upon contact, and is , potentially leading to , central nervous system effects, and organ damage. It poses environmental risks as a very toxic substance to aquatic life and is classified under for corrosivity, (irritant), and environmental hazard. Global production exceeds tens of thousands of tonnes annually, primarily in countries like , , and the , reflecting its essential industrial status balanced against health and ecological precautions.

Properties

Physical properties

Resorcinol is a white crystalline solid with the molecular formula C₆H₆O₂ and of 110.11 g/mol. It appears as colorless or white needles, plates, or powder, though impure samples may turn pink upon exposure to air and light. The compound is hygroscopic, readily absorbing moisture from the atmosphere. Resorcinol melts at 110 °C and boils at 280 °C under standard pressure. Its density is 1.28 g/cm³ at room temperature. The vapor pressure is low, measuring 0.065 Pa at 20 °C, indicating limited volatility.
PropertyValue
Solubility in water140 g/100 mL at 20 °C
Solubility in ethanolMiscible
Solubility in etherSoluble
Resorcinol exhibits high solubility in water and polar organic solvents such as alcohols and ethers, but limited solubility in nonpolar solvents. It remains stable under standard storage conditions, though protection from light and moisture is recommended to prevent discoloration.

Chemical properties

Resorcinol, systematically named 1,3-benzenediol, exhibits weak acidity characteristic of , with the two hydroxyl groups dissociating sequentially. The first corresponds to a pKa of 9.32, while the second has a pKa of 11.1, enabling formation of mono- and dianionic species upon reaction with strong bases such as . These values reflect stabilization of the phenolate anions through resonance delocalization of the negative charge into the aromatic ring, more pronounced than in aliphatic alcohols but less so than in carboxylic acids. The meta positioning of the hydroxyl groups precludes strong intramolecular hydrogen bonding, distinguishing resorcinol from its 1,2-isomer (), where such bonding stabilizes the ortho configuration. Instead, resorcinol primarily forms intermolecular hydrogen bonds, contributing to its solid-state packing and solubility in polar solvents. The phenolic protons participate in hydrogen bonding as donors, while the oxygen atoms act as acceptors, influencing and acid-base equilibria in aqueous media. Resorcinol demonstrates keto-enol tautomerism, with the enol form overwhelmingly predominant due to the aromatic stabilization of the ring; the keto tautomer, involving migration of a to a ring carbon and carbonyl formation, is energetically unfavorable under standard conditions. This preference underscores the compound's inherent and integrity. The electron-donating effect of the hydroxyl groups increases ring electron density, particularly at positions ortho and para to them, rendering the aromatic system more nucleophilic than that of or monophenols, though the meta arrangement modulates activation relative to vicinal dihydroxybenzenes.

Synthesis and Production

Industrial methods

The primary industrial method for resorcinol production is the sulfonation-alkali fusion process, involving the sequential sulfonation of to benzene-1,3-disulfonic acid followed by fusion with . is first treated with concentrated at approximately 100 °C to form benzenesulfonic acid, which is then further sulfonated using 65% at 80-85 °C to yield the meta-disulfonic acid selectively. The disulfonic acid is subsequently fused with molten caustic soda at temperatures around 300 °C, displacing the sulfonic acid groups with hydroxyl groups to form sodium resorcinolate, which is isolated by acidification with such as hydrochloric or . This process, the oldest commercial route dating back to the early , achieves overall yields of approximately 90% in optimized modern variants, with product purity exceeding 99% through purification steps like under . An alternative industrial route utilizes the acid-catalyzed of m-phenylenediamine (m-PD), sourced from the reduction of m-dinitrobenzene derived via meta-selective of . m-PD is hydrolyzed in the presence of strong mineral acids such as at elevated temperatures (typically 150-200 °C), promoting to resorcinol with high selectivity and yields often surpassing 90%, facilitated by catalysts like zeolites in some proprietary processes to minimize byproducts such as resins. This method has gained prominence for its efficiency in avoiding sulfonation byproducts and enabling integration with nitroaromatic production streams, though it requires careful control to manage corrosive conditions and impurity formation. Global resorcinol production, exceeding tens of thousands of tons annually, is dominated by a few key producers including , the world's largest manufacturer with ISO-certified facilities emphasizing environmental controls, alongside Mitsui Chemicals and INDSPEC Chemical Corporation. Economic viability of these processes hinges on raw material costs ( and acids), energy-intensive fusion or steps, and demand-driven scaling, with modern optimizations focusing on waste minimization and higher throughput to achieve purity levels above 99.5% for and intermediates.

Laboratory preparation

One laboratory method for preparing resorcinol involves the selective extraction and fusion of natural resins such as or , where the compound is isolated through or treatment, a technique historically used since the mid-19th century for small-scale production. A standard synthetic route starts with the reduction of 3-nitrophenol to 3-aminophenol using reagents like iron and or catalytic , followed by diazotization of the group with in acidic medium at 0-5°C, and then of the resulting diazonium salt under aqueous conditions at 80-100°C to introduce the second hydroxy group, affording resorcinol in yields typically ranging from 70% to 80% after . Purification of the crude product is achieved via (boiling point approximately 276°C at , lower under reduced pressure to avoid decomposition) or recrystallization from hot or , ensuring removal of byproducts like or amines. An alternative approach employs the acid-catalyzed of m-phenylenediamine, where sulfuric or facilitates the replacement of one amino group with a at temperatures of 200-250°C under pressure, delivering resorcinol in yields up to 75% with molar acid-to-substrate ratios of 1.6-1.8, suitable for bench-scale reactions due to its simplicity despite corrosive conditions.

Chemical Reactions

Electrophilic aromatic substitution

Resorcinol exhibits markedly enhanced reactivity toward relative to phenol, attributable to the dual activation by its two hydroxy groups, which donate to the ring via . These groups, located at the 1 and 3 positions, impose strong ortho/para directing effects, favoring substitution at the 2-position (ortho to both) and the equivalent 4- and 6-positions (ortho to one and para to the other). This arises because the sigma complex intermediates at these sites benefit from stabilization by both oxygen lone pairs, lowering the compared to other positions. Halogenation proceeds rapidly under mild conditions; for instance, treatment with in aqueous media yields 2,4,6-tribromoresorcinol as the predominant product due to successive substitutions at the activated sites, often without need for catalysts. Monosubstitution, such as at the 4-position, requires of one (e.g., as a benzoate ester) to mitigate over-halogenation. similarly targets the 4-position initially with dilute , but progresses to polynitration under forcing conditions, reflecting the ring's propensity for multiple electrophilic attacks. Sulfonation occurs analogously, with fuming affording 2,4,6-trisulfoderivatives. Reaction rates for resorcinol in such processes exceed those of phenol by significant margins, as evidenced in acid-catalyzed hydrogen-deuterium exchange and condensation kinetics, where resorcinol's rate constants are substantially higher under comparable conditions.

Oxidation and other reactions

Resorcinol undergoes auto-oxidation upon exposure to air and light, resulting in discoloration due to the formation of polymeric or quinone-like products. This process occurs at ambient temperatures around 25°C and is incompatible with certain metal salts, such as iron, which may accelerate oxidation. In biological systems, enzymatic oxidation by resorcinol hydroxylase in denitrifying bacteria like Azoarcus anaerobius converts resorcinol to hydroxyhydroquinone (1,2,4-trihydroxybenzene) under anaerobic conditions, using nitrate or ferricyanide as electron acceptors, as an initial step in degradation pathways. Electrochemical oxidation of resorcinol in aqueous media proceeds via one-electron or proton-coupled electron transfer to generate radicals, which dimerize or form further oxidized species, though meta-benzoquinone intermediates are thermodynamically unstable. Resorcinol forms ethers through with alkyl halides, typically via the Williamson synthesis involving to the phenoxide ion, allowing mono- or dialkylation depending on conditions; selective monotherification requires controlled or protecting groups to avoid symmetrical products. Esterification occurs with carboxylic acids or their derivatives, such as in the reaction with hindered benzoic acids to yield resorcinol esters, often catalyzed by acids or via acylium intermediates, though resorcinol's phenolic hydroxyls limit yields under standard conditions without activation. A prominent miscellaneous reaction is the polycondensation with under acidic or basic , forming resorcinol-formaldehyde resins with methylene bridges primarily at the 4- and 6-positions relative to the hydroxyls, yielding water-soluble adhesives or ion-exchange materials with high reactivity due to resorcinol's activated ring. Reductive transformations are uncommon but include catalytic to 1,3-cyclohexanedione derivatives under specific conditions. Resorcinol exhibits limited stability toward strong oxidants, reacting explosively with concentrated or other vigorous agents to produce hazardous byproducts.

Natural Occurrence

Biological sources

Resorcinol derivatives, particularly alkylresorcinols, are biosynthesized in , , fungi, and via type III enzymes that condense fatty acid-derived chains with units to form the resorcinol core. These phenolic lipids accumulate in tissues such as bran (e.g., and , where they constitute up to 0.1-0.3% of dry weight) and root exudates, functioning as defense compounds against pathogens. In fungi, resorcinol-based metabolites like chaetorcinol have been isolated from species such as aureum, typically at trace levels below 1% of extractable compounds. Cyanobacteria produce halogenated alkylresorcinols, such as those in the bartoloside family, through similar pathways, often as part of complex polyketide-natural product assemblies with roles in chemical and UV protection. Bacterial follows analogous routes, yielding dialkylresorcinols with chain lengths of 15-21 carbons, confirmed by genomic and enzymatic studies in genera like . Empirical isolation of these compounds dates to the late , with early reports from plant-derived resins and microbial cultures validating their endogenous production rather than artifactual formation. Overall, free resorcinol occurs in minute quantities (<0.01% in most cases), primarily as a biosynthetic intermediate or degradation product within these organisms, underscoring its evolutionary conservation for stress response rather than bulk accumulation.

Environmental presence

Resorcinol enters aquatic environments primarily through industrial effluents from dye manufacturing, adhesive production, and resin synthesis facilities. It has been detected as a pollutant in wastewater and filtered groundwater near waste treatment plants associated with these operations. Concentrations in such effluents typically remain at trace levels due to treatment processes, though specific measurements in parts per billion have been reported in contaminated industrial discharges. In water, resorcinol exhibits rapid biodegradation under aerobic conditions, with half-lives ranging from 0.16 to 0.24 days in activated sludge tests and approximately 0.5 days in aerobic soil environments. This short persistence limits long-term accumulation in surface waters, facilitated by its high water solubility (miscible at 20°C) and susceptibility to microbial degradation. Anaerobic degradation is also feasible, though slower than aerobic pathways. Accumulation in soils and sediments is minimal, as resorcinol's polarity and solubility favor partitioning into aqueous phases over sorption to solids, combined with complete degradation observed within 8 days in silt loam soils inoculated with mineral salts medium. Atmospheric presence is negligible owing to its low vapor pressure (4.9 × 10^{-4} mm Hg at 25°C), which restricts volatilization; any airborne releases degrade rapidly via reaction with hydroxyl radicals, with a half-life of about 2 hours in the upper atmosphere. Global emissions from production and use are estimated at 22.4 tonnes per year, with European contributions at 6.75 tonnes annually, reflecting low-release practices by manufacturers. Environmental monitoring occurs under frameworks like EU REACH, employing methods such as high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) for detection in effluents and receiving waters.

Applications

Industrial applications

Resorcinol serves as a key monomer in the production of resorcinol-formaldehyde (RF) and phenol-resorcinol-formaldehyde (PRF) resins, which are employed as adhesives in industrial manufacturing. These resins are particularly valued for their ability to form waterproof, high-strength bonds in applications such as plywood production and structural wood laminates, where they provide durability under wet conditions superior to many phenolic alternatives. In tire and mechanical rubber goods manufacturing, resorcinol-based adhesives, often in the form of resorcinol-formaldehyde-latex (RFL) systems, enhance adhesion between rubber compounds and reinforcing cords like nylon or polyester, improving overall tire performance and longevity. As a chemical intermediate, resorcinol is utilized in the synthesis of azo dyes, including mordant and diazo variants, where its phenolic structure facilitates coupling reactions to produce colorants for textiles and other materials. It also contributes to UV stabilizers incorporated into polymers, protecting materials from photodegradation by absorbing ultraviolet radiation effectively due to its conjugated system. In leather processing, resorcinol functions as a tanning agent, often through complexes with metals or in combination with formaldehyde for retanning mineral-tanned hides, yielding leathers with improved flexibility and water resistance. Additionally, resorcinol derivatives serve as flame retardants and antioxidants in rubber formulations, mitigating oxidative degradation and enhancing fire resistance in industrial rubber products. In 1977 U.S. consumption data, approximately 65% of resorcinol went to rubber products, underscoring its prominence in these sectors.

Medical and pharmaceutical applications

Resorcinol serves as a topical keratolytic agent for treating acne vulgaris and hyperkeratosis, typically formulated at concentrations up to 2% in anti-acne preparations to promote desquamation of the stratum corneum. Its mechanism involves loosening intercellular bonds in the epidermal layer, aiding removal of hyperkeratotic scales and clogged pores through mild cytotoxic effects on keratinocytes. In antiseptic applications, resorcinol has been incorporated into wound dressings and dermatological ointments since the late 19th century, leveraging its disinfectant properties against skin pathogens. Contemporary over-the-counter formulations continue this role, often combined with sulfur for enhanced efficacy in reducing inflammatory lesions associated with acne and seborrheic dermatitis. Clinical evidence supports resorcinol's therapeutic value in hidradenitis suppurativa, a condition involving hyperkeratotic and infectious elements; 15% topical resorcinol achieved significant improvements in Hurley stage and clinical response scores, with over 80% lesion resolution reported in treated patients after one month. Similarly, 10% resorcinol demonstrated superior lesion reduction compared to 1% clindamycin in mild cases, with favorable tolerability and reduced need for antibiotics. Resorcinol exhibits tyrosinase inhibitory activity by binding to the enzyme's dicopper center, potentially mitigating hyperpigmentation via reduced melanin production, though clinical applications remain topical due to negligible systemic absorption and aversion to oral routes from documented gastrointestinal irritation. No systemic pharmaceutical approvals exist for resorcinol.

Consumer products

Resorcinol serves as a coupling agent in oxidative hair dyes, facilitating color development when mixed with primary intermediates and hydrogen peroxide. In the European Union, the Scientific Committee on Consumer Safety (SCCS) has established a maximum concentration of 1.25% (as free base) in such products intended for hair and eyelashes after 1:1 mixing under oxidative conditions. It is also permitted in hair lotions and shampoos at up to 0.5%, where it contributes to formulation stability or mild coloring effects. In over-the-counter acne treatments, resorcinol is formulated at concentrations up to 2% to keratolytically remove scaly or rough skin associated with mild acne. These consumer products are applied topically, often combined with sulfur for enhanced efficacy against pimples and comedones. Consumer exposure to resorcinol from these products is predominantly dermal. For hair dyes, systemic exposure is estimated at 0.03 mg/kg body weight per treatment, assuming 100 ml applied for 30 minutes monthly with low absorption rates around 0.076%. Acne creams may yield higher daily exposures of up to 0.4 mg/kg body weight, based on 800 mg applied daily and 2.87% dermal absorption. Shampoo use contributes minimally due to rinse-off application and lower concentrations.

Safety, Toxicology, and Environmental Impact

Human health effects

Resorcinol causes skin and eye irritation upon acute exposure, with concentrations above 1% leading to moderate to severe dermal erythema and ocular damage in human subjects. Oral acute toxicity in rats yields an LD50 of approximately 300 mg/kg, manifesting as convulsions, ataxia, and methemoglobinemia at higher doses. In humans, methemoglobinemia has been reported following topical application of high-concentration formulations (e.g., 3% in creams) or excessive oral ingestion exceeding 1 g/kg, particularly in infants due to immature methemoglobin reductase activity, resulting in cyanosis and hemolytic anemia treatable with methylene blue. Chronic oral exposure in rodents at doses exceeding 200 mg/kg/day inhibits thyroid peroxidase and iodide uptake, causing reversible goiter and hypothyroidism without progression to neoplasia or permanent gland damage upon cessation. No adverse reproductive or developmental effects occur at exposure levels relevant to human dermal or incidental ingestion scenarios, with studies showing no teratogenicity in rats up to 200 mg/kg/day. Resorcinol exhibits moderate dermal sensitization potential in animal models but low incidence in human patch tests, with positive reactions below 1% across clinical cohorts tested at 0.1-1% concentrations. Genotoxicity assays, including the Ames bacterial reverse mutation test and in vitro micronucleus evaluation, demonstrate negative results, indicating no mutagenic or clastogenic activity.

Regulatory assessments

The Scientific Committee on Consumer Safety (SCCS) of the European Union assessed resorcinol in 2021 and concluded it is safe for use as an oxidative hair dye ingredient in cosmetic products applied to hair and eyelashes at concentrations up to 1.25%, despite evaluating potential endocrine disrupting properties; the committee found insufficient evidence of thyroid hormone disruption or other adverse effects at human exposure levels from such uses. The International Agency for Research on Cancer (IARC) classifies resorcinol in Group 3, not classifiable as to its carcinogenicity to humans, based on inadequate evidence in humans and animals as of its 1999 evaluation. In the United States, the Environmental Protection Agency (EPA) derived a reference dose of 0.2 mg/kg/day for chronic oral exposure to resorcinol, using a no-observed-adverse-effect level (NOAEL) of 34 mg/kg/day for thyroid effects observed in a 91-day rat study, with an uncertainty factor of 100 to account for interspecies and intraspecies variability; this value provides a margin exceeding typical consumer exposures by orders of magnitude. Reviews of endocrine disruption claims highlight that thyroid and related effects manifest only at doses substantially higher than environmental or consumer levels—often >100-fold greater—with no causal links demonstrated in human epidemiology for low-dose scenarios or ancillary concerns like central nervous system impacts. Under the EU's REACH regulation, resorcinol is registered for industrial, cosmetic, and other uses with tonnage-based reporting and substance evaluation requirements, including amphibian developmental testing; proposals to designate it as a for endocrine disruption were rejected by the Member State Committee in 2022, citing inadequate evidence of serious effects in humans at relevant exposures, allowing continued authorized applications subject to monitoring.

Ecological and environmental effects

Resorcinol exhibits moderate toward aquatic biota, with 96-hour LC50 values for fish (e.g., mykiss) ranging from 31 to 56 mg/L and values for algae (Pseudokirchneriella subcapitata) around 97 mg/L. Chronic exposure impacts invertebrate reproduction, with NOEC for at 10 mg/L in 21-day tests, leading to classification as harmful to aquatic life with long-lasting effects (H412). These metrics indicate potential short-term disruption in high-exposure scenarios but limited broad risk at environmental concentrations. Resorcinol undergoes rapid aerobic , achieving over 70% BOD removal in 5 days via river water die-away assays and complete degradation within 8 days under MITI conditions at 30 mg/L. Its low (log Kow = 0.80) correlates with negligible , evidenced by a factor (BCF) of 3.16 in . Resorcinol lacks persistence as a potential organic and shows no ozone-depleting activity, facilitating natural attenuation in oxic environments. Wastewater treatment via processes removes over 90% of resorcinol through microbial degradation, as demonstrated in sequential batch reactors and constructed wetlands achieving 94% efficiency at influent levels of 10 mg/L. Field observations from industrial effluents, including rubber and dye production sites, reveal minimal long-term or community-level disruptions, attributable to its favorable fate properties and dilution in receiving waters.

History and Nomenclature

Discovery and early isolation

Resorcinol, or benzene-1,3-diol, was first isolated in 1864 by Austrian chemists Heinrich Hlasiwetz and Ludwig Barth through the of resin, a gum obtained from the plant. Hlasiwetz, working at the , heated the resin to produce a phenolic distillate, which upon purification yielded resorcinol as white crystals with characteristic properties such as solubility in water and formation of colored derivatives with ferric chloride. This isolation followed earlier experiments by Hlasiwetz in 1851 on similar resins, marking resorcinol as the third isomeric dihydroxybenzene identified after (1843) and (1861). The of resorcinol as 1,3-dihydroxy was confirmed through synthetic routes and degradation studies in the ensuing decades. Early characterizations involved its conversion to known derivatives, distinguishing it from ortho- and para-isomers via (110 °C) and reactivity patterns, such as preferential sulfonation at the 4-position. By the 1870s, synthesis via fusion of meta-benzenedisulfonic acid—prepared by sulfonation of with fuming followed by alkaline melting—provided a laboratory-scale route, enabling structural verification independent of natural sources. Industrial interest in resorcinol grew in the early alongside the expansion of the synthetic sector, where it served as a agent in production, prompting scaled-up sulfonation-fusion methods. Production spiked during due to demand for resorcinol-formaldehyde resins in weather-resistant adhesives for wooden aircraft, notably the , whose plywood laminates relied on resorcinol glues for structural integrity under combat stresses. By the 1940s, refinements in the sulfonation process, including catalyst-assisted sulfonation and optimized fusion conditions, facilitated commercial viability, with patents detailing yields exceeding 70% from feedstock.

Etymology and naming conventions

The name resorcinol derives from "resin," alluding to its original isolation from ammoniated resin gums such as those of tropical trees, combined with "orcinol," a structurally similar compound obtained from orcin (a dye extracted from lichens of the Rocella genus). This portmanteau was coined in the 19th century to reflect both the source material and chemical kinship, with the suffix "-ol" denoting its phenolic nature. The is benzene-1,3-diol, emphasizing the positions of the hydroxyl groups on the ring. Alternative designations include 1,3-benzenediol, m-dihydroxybenzene (indicating the meta substitution pattern), and occasionally resorcin in early chemical texts. Older literature may reference variants like pyroresorcinol, tied to pyrolytic preparation methods from organic resins. In contrast to its dihydroxybenzene isomers—catechol (benzene-1,2-diol, named after extraction from gum) and hydroquinone (benzene-1,4-diol, from its reduction of )—the trivial name resorcinol uniquely highlights derivation from resinous natural products rather than dye or tanning sources. This nomenclature convention underscores the historical emphasis on isolation origins in early , prior to widespread adoption of systematic naming.

Isomeric dihydroxybenzenes

(1,2-dihydroxybenzene), resorcinol (1,3-dihydroxybenzene), and (1,4-dihydroxybenzene) constitute the three positional isomers of dihydroxy, differing in the relative placement of hydroxyl groups on the ring, which influences their electronic distribution, reactivity, and applications. These structural variations lead to distinct behaviors in oxidation, where and readily undergo conversion to ortho- and para-quinones, respectively, due to favorable tautomerization, whereas resorcinol resists such oxidation owing to the meta configuration impeding stabilization. The meta arrangement in resorcinol enhances (EAS) reactivity, as both hydroxyl groups ortho-para direct to shared positions (e.g., carbons 4 and 6), promoting rapid polysubstitution without the intramolecular hydrogen bonding that moderates reactivity in or the symmetry-constrained activation in . In contrast, 's adjacent hydroxyls facilitate stronger with metal ions via five-membered ring formation, a capability diminished in the meta and para isomers due to suboptimal for bidentate coordination. Toxicity profiles vary empirically, with resorcinol exhibiting milder acute effects than in models across oral, dermal, and routes, attributed to lower systemic absorption and metabolic interference; shows intermediate dermal irritancy but higher potential. Solubilities in at 20°C reflect bonding efficiency: resorcinol exceeds 100 g/100 mL, approximately 35 g/100 mL, and around 7 g/100 mL, influencing their handling in aqueous processes. Industrial selections leverage these traits: catechol's oxidation propensity and suit synthesis for processing, while hydroquinone's cycling supports its role as a ; resorcinol's elevated EAS reactivity favors in precursors over the alternatives' tendencies toward oxidation or reduced substitution rates.
PropertyCatechol (1,2-)Resorcinol (1,3-)Hydroquinone (1,4-)
Oxidation pronenessHigh (o-quinone formation)Low (no stable quinone)High (p-quinone formation)
EAS reactivityModerate (H-bonding hindrance)High (cooperative activation)Moderate (symmetry effects)
Chelation abilityStrong (adjacent OH)Weak (meta spacing)Moderate (para spacing)
Acute toxicity (relative)Higher than resorcinolMilderIntermediate
Water solubility (g/100 mL, 20°C)~35>100~7

Derivatives and analogs

Orcinol, also known as 5-methylresorcinol, is an alkyl-substituted derivative of resorcinol featuring a at the 5-position, which occurs naturally as a in certain species and in lichens such as those from the genus Lecanora. This compound retains the 1,3-dihydroxybenzene core but exhibits modified solubility and reactivity due to the alkyl substitution, influencing its role in and potential applications in and research. 4-Hexylresorcinol represents a longer-chain alkyl with a hexyl group at the 4-position, synthesized through of resorcinol, and demonstrates enhanced efficacy compared to unsubstituted resorcinol, as bactericidal activity increases with alkyl chain length, a relationship established in syntheses dating to 1921. It possesses local anesthetic and properties attributable to the lipophilic alkyl extension, which improves interaction while preserving the phenolic hydroxyl groups essential for bioactivity. Alkylresorcinols, encompassing both natural and semi-synthetic variants with varying chain lengths at the 4- or 5-position, are lipophilic polyphenols produced by , fungi, and , where the alkyl chain modulates antimicrobial potency; for instance, retention of phenolic hydrogens is critical for bactericidal effects, with dialkyl derivatives showing reduced activity upon their modification. In structure-activity studies, the meta-positioning of hydroxyl groups in these resorcinol-based scaffolds enhances selectivity for like inhibition or bacterial enzymes, distinct from ortho- or para-dihydroxybenzene analogs, while alkyl extensions at C4 or C5 improve and antimycobacterial potential against strains such as species through disrupted cell envelope integrity. Orcinol-type structures appear in certain plant-derived and resorcinol derivatives, such as those isolated from Ononis , where the alkyl-substituted resorcinol unit contributes to inhibitory activity and potential therapeutic effects, though synthetic analogs often outperform natural isolates in potency due to optimized chain lengths.

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