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Mesitylene
Mesitylene
Mesitylene
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Mesitylene
Mesitylene
Mesitylene
Mesitylene
Mesitylene
Names
Preferred IUPAC name
1,3,5-Trimethylbenzene[1]
Other names
Mesitylene[1]
sym-Trimethylbenzene
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.003.278 Edit this at Wikidata
EC Number
  • 203-604-4
KEGG
UNII
UN number 2325
  • InChI=1S/C9H12/c1-7-4-8(2)6-9(3)5-7/h4-6H,1-3H3 checkY
    Key: AUHZEENZYGFFBQ-UHFFFAOYSA-N checkY
  • InChI=1/C9H12/c1-7-4-8(2)6-9(3)5-7/h4-6H,1-3H3
    Key: AUHZEENZYGFFBQ-UHFFFAOYAK
  • Cc1cc(cc(c1)C)C
Properties
C9H12
Molar mass 120.19 g/mol
Appearance Colorless liquid[2]
Odor Distinctive, aromatic[2]
Density 0.8637 g/cm3 at 20 °C
Melting point −44.8 °C (−48.6 °F; 228.3 K)
Boiling point 164.7 °C (328.5 °F; 437.8 K)
0.002% (20°C)[2]
Vapor pressure 2 mmHg (20°C)[2]
−92.32·10−6 cm3/mol
Structure
0.047 D[3]
Hazards
Flash point 50 °C; 122 °F; 323 K[2]
NIOSH (US health exposure limits):
PEL (Permissible)
 none[2]
REL (Recommended)
 TWA 25 ppm (125 mg/m3)[2]
IDLH (Immediate danger)
 N.D.[2]
Safety data sheet (SDS) [1]
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 ?)

Mesitylene or 1,3,5-trimethylbenzene is a derivative of benzene with three methyl substituents positioned symmetrically around the ring. The other two isomeric trimethylbenzenes are 1,2,4-trimethylbenzene (pseudocumene) and 1,2,3-trimethylbenzene (hemimellitene). All three compounds have the formula C6H3(CH3)3, which is commonly abbreviated C6H3Me3. Mesitylene is a colorless liquid with sweet aromatic odor. It is a component of coal tar, which is its traditional source. It is a precursor to diverse fine chemicals. The mesityl group (Mes) is a substituent with the formula C6H2Me3 and is found in various other compounds.[4]

Preparation

[edit]

Mesitylene is prepared by transalkylation of xylene over solid acid catalyst:[4]

2 C6H4(CH3)2 ⇌ C6H3(CH3)3 + C6H5CH3
C6H4(CH3)2 + CH3OH → C6H3(CH3)3 + H2O

Although impractical, it could be prepared by trimerization of propyne, also requiring an acid catalyst, which yields a mixture of 1,3,5- and 1,2,4-trimethylbenzenes.

Trimerization of acetone via aldol condensation, which is catalyzed and dehydrated by sulfuric acid is another method of synthesizing mesitylene.[5]

Reactions

[edit]

Oxidation of mesitylene with nitric acid yields trimesic acid, C6H3(COOH)3. Using manganese dioxide, a milder oxidising agent, 3,5-dimethylbenzaldehyde is formed. Mesitylene is oxidised by trifluoroperacetic acid to produce mesitol (2,4,6-trimethylphenol).[6] Bromination occurs readily, giving mesityl bromide:[7]

(CH3)3C6H3 + Br2 → (CH3)3C6H2Br + HBr

Mesitylene is a ligand in organometallic chemistry, one example being the organomolybdenum complex [(η6-C6H3Me3)Mo(CO)3][8] which can be prepared from molybdenum hexacarbonyl.

Applications

[edit]

Mesitylene is mainly used as a precursor to 2,4,6-trimethylaniline, a precursor to colorants. This derivative is prepared by selective mononitration of mesitylene, avoiding oxidation of the methyl groups.[9]

Niche uses

[edit]
Structure of (mesitylene)molybdenum tricarbonyl, [(η6-C6H3Me3)Mo(CO)3]

Mesitylene is used in the laboratory as a specialty solvent. In the electronics industry, mesitylene has been used as a developer for photopatternable silicones due to its solvent properties.

The three aromatic hydrogen atoms of mesitylene are in identical chemical shift environments. Therefore, they only give a single peak near 6.8 ppm in the 1H NMR spectrum; the same is also true for the nine methyl protons, which give a singlet near 2.3 ppm. For this reason, mesitylene is sometimes used as an internal standard in NMR samples that contain aromatic protons.[10]

Uvitic acid is obtained by oxidizing mesitylene or by condensing pyruvic acid with baryta water.[11]

The Gattermann reaction can be simplified by replacing the HCN/AlCl3 combination with zinc cyanide (Zn(CN)2).[12] Although it is highly toxic, Zn(CN)2 is a solid, making it safer to work with than gaseous hydrogen cyanide (HCN).[13] The Zn(CN)2 reacts with the HCl to form the key HCN reactant and ZnCl2 that serves as the Lewis-acid catalyst in-situ. An example of the Zn(CN)2 method is the synthesis of mesitaldehyde from mesitylene.[14]

History

[edit]

Mesitylene was first prepared in 1837 by Robert Kane, an Irish chemist, by heating acetone with concentrated sulfuric acid.[15] He named his new substance "mesitylene" because the German chemist Carl Reichenbach had named acetone "mesit" (from the Greek μεσίτης, the mediator),[16] and Kane believed that his reaction had dehydrated mesit, converting it to an alkene, "mesitylene".[17] However, Kane's determination of the chemical composition ("empirical formula") of mesitylene was incorrect. The correct empirical formula was provided by August W. von Hofmann in 1849.[18] In 1866 Adolf von Baeyer gave a correct mesitylene's empirical formula; however, with a wrong structure of tetracyclo[3.1.1.11,3.13,5]nonane.[19] A conclusive proof that mesitylene was trimethylbenzene was provided by Albert Ladenburg in 1874; however, assuming wrong benzene structure of prismane.[20]

  • Historical mesitylene structures
  • Mesitylene by Adolf von Baeyer (tetracyclo[3.1.1.11,3.13,5]nonane)
    Mesitylene by Adolf von Baeyer (tetracyclo[3.1.1.11,3.13,5]nonane)
  • Mesitylene by Albert Ladenburg (1,2,6-trimethylprismane)
    Mesitylene by Albert Ladenburg (1,2,6-trimethylprismane)

Mesityl group

[edit]
See also: Tetramesityl compounds

The group (CH3)3C6H2- is called mesityl (organic group symbol: Mes). Mesityl derivatives, e.g. tetramesityldiiron, are typically prepared from the Grignard reagent (CH3)3C6H2MgBr.[21] Due to its large steric demand, the mesityl group is used as a large blocking group in asymmetric catalysis (to enhance diastereo- or enantioselectivity) and organometallic chemistry (to stabilize low oxidation state or low coordination number metal centers). Larger analogues with even greater steric demand, for example 2,6-diisopropylphenyl (Dipp) and the analogously named Tripp ((iPr)3C6H2, Is) and supermesityl ((tBu)3C6H2, Mes*) groups, may be even more effective toward achieving these goals.

Safety and the environment

[edit]

Mesitylene is also a major urban volatile organic compound (VOC) which results from combustion. It plays a significant role in aerosol and tropospheric ozone formation as well as other reactions in atmospheric chemistry.[citation needed]

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Mesitylene

View on Grokipedia
from Grokipedia
Mesitylene, systematically named 1,3,5-trimethylbenzene, is a colorless, flammable liquid with the molecular C₉H₁₂, serving as one of three isomers distinguished by its symmetric arrangement of three methyl groups on a ring. It exhibits a of -44.8 °C, a of 164.7 °C, a of 0.8637 g/cm³ at 20 °C, and low in (48.2 mg/L at 25 °C), rendering it insoluble and less dense than , with a of 50 °C. This compound is notable for its stability and aromatic properties, making it a versatile intermediate in . Mesitylene is primarily produced through , where it emerges as a component of C9 aromatic fractions during the and reforming of crude oil, often comprising a portion of mixed streams. High-purity mesitylene can also be synthesized via the and of acetone in the presence of or obtained from distillates, allowing for tailored production to meet industrial specifications; recent advancements include renewable production from biomass-derived acetone for applications like additives. Historically, it has been isolated from natural sources like , with commercial separation involving and extraction techniques to purify it from other isomers such as . In industrial applications, mesitylene functions as a key building block for manufacturing plastics, dyes, and resins, as well as UV stabilizers and antioxidants to enhance material durability. It serves as a in paints, thinners, and coatings, and is incorporated into automobile fuels and rubber production for its solvency and stabilizing effects. In research and specialized uses, mesitylene acts as a in organometallic reactions, a developer in , and an intermediate for plasticizers, adhesives, and the synthesis of . Due to its flammability and potential , mesitylene poses risks including to the skin, eyes, and upon exposure, with or potentially causing ; the NIOSH recommended exposure limit is 25 ppm as a 10-hour time-weighted average. Environmentally, it is harmful to aquatic life and can bioaccumulate, necessitating careful handling and regulatory oversight in production and use.

Chemical Identity

Nomenclature

The for mesitylene is 1,3,5-trimethylbenzene (CAS 108-67-8). This compound is commonly referred to as mesitylene, a name coined by Irish chemist Robert Kane upon its first synthesis (prepared in 1837, published 1838) from acetone and . The term derives from "mesityl," itself stemming from the early name "mesit" for acetone, which originates from mesitēs (μεσίτης), meaning "," reflecting the compound's perceived intermediate role in chemical transformations and its symmetrical positioning it as a "middle" entity among aromatic hydrocarbons. It is also known as sym-trimethylbenzene, emphasizing the symmetric placement of its three methyl groups. Other synonyms include the abbreviation 1,3,5-TMB. Mesitylene must be distinguished from the other trimethylbenzene isomers: 1,2,3-trimethylbenzene (hemimellitene) and (pseudocumene).

Molecular Structure

Mesitylene has the C₉H₁₂ and consists of a ring with three methyl groups attached at the 1, 3, and 5 positions, creating a highly symmetric structure. This arrangement imparts D_{3h} point group to the molecule, arising from its planar geometry, a principal C₃ rotation axis perpendicular to the ring, and horizontal mirror planes that include the molecular plane and bisect the ring. Typical bond lengths in the structure include approximately 1.39 for the aromatic C-C bonds within the ring and about 1.50 for the bonds connecting the ring carbons to the methyl groups, as determined from computational models. The high results in a very small dipole moment of 0.10 D, rendering the molecule nearly nonpolar. The positioning of the methyl groups introduces significant steric hindrance at the 2, 4, and 6 positions of the ring, where the ortho hydrogens relative to each methyl are effectively shielded, influencing reactivity patterns.

Physical and Thermodynamic

Appearance and Basic

Mesitylene appears as a colorless at standard and pressure, exhibiting a distinctive sweet and aromatic that is characteristic of many alkylbenzenes. This physical form stems from its relatively low , allowing it to remain under ambient conditions. The compound's low polarity, arising from its highly symmetric molecular structure with three methyl groups symmetrically substituted on the ring, contributes to its limited interaction with polar solvents like while favoring with nonpolar organic media. Key physical properties of mesitylene are summarized in the following table:
PropertyValueConditionsSource
Molecular weight120.19 g/mol-PubChem
Melting point-44.8 °C-PubChem; O'Neil, M.J., ed. The Merck Index, 14th ed. (2006)
Boiling point164.7 °C1 atm (760 mmHg)PubChem; O'Neil, M.J., ed. The Merck Index, 14th ed. (2006)
Density0.8637 g/cm³20 °CPubChem; O'Neil, M.J., ed. The Merck Index, 14th ed. (2006)
Vapor pressure2 mmHg20 °CPubChem; NIOSH Pocket Guide to Chemical Hazards (2024)
Vapor density4.1vs. air = 1PubChem; NIOSH Pocket Guide to Chemical Hazards (2024)
Solubility in water0.002 g/100 mL20 °CPubChem; O'Neil, M.J., ed. The Merck Index, 14th ed. (2006)
Solubility in organic solventsMisciblee.g., ethanol, etherPubChem
Flash point50 °Cclosed cupPubChem; NIOSH Pocket Guide to Chemical Hazards (2024)
These properties indicate mesitylene's utility as a nonpolar , with its volatility and flammability necessitating careful handling in laboratory and industrial settings.

Spectroscopic and Other Properties

Mesitylene exhibits characteristic spectroscopic features due to its symmetric 1,3,5-trisubstituted structure. In ¹H NMR spectroscopy, the three equivalent aromatic protons appear as a singlet at 6.78 ppm (3H), while the nine equivalent methyl protons resonate as a singlet at 2.26 ppm (9H) in CDCl₃ . This high symmetry results in only two distinct signals, simplifying the spectrum and making mesitylene a useful in NMR analyses of samples containing aromatic protons, as its sharp, non-overlapping peaks allow accurate quantification. The (IR) spectrum of mesitylene displays key absorptions indicative of its functional groups. Aromatic C-H vibrations occur in the 3000–3100 cm⁻¹ region, typical for sp²-hybridized C-H bonds in derivatives. Additionally, the symmetric deformation of the methyl groups (C-CH₃) is observed around 1370 cm⁻¹, reflecting the aliphatic substituents on the ring. In ultraviolet-visible (UV-Vis) , mesitylene shows absorption maxima near 258 nm, 263 nm, 267 nm (log ε = 2.2), and 273 nm (log ε = 2.3) in alcohol solvent, attributed to π-π* transitions in the aromatic system. The bathochromic shift relative to arises from the electron-donating methyl groups, which increase the electron density in the π-system. Thermodynamic properties of mesitylene include a heat of vaporization of approximately 43.5 kJ/mol at its of 164.7 °C. The of the phase is 200.5 J/mol·K at 25 °C, reflecting its molecular complexity compared to simpler hydrocarbons. Optical and transport properties further characterize mesitylene as a . Its is 1.499 at 20 °C (n_D), consistent with its nonpolar aromatic nature. The dynamic is 0.66 mPa·s at 25 °C, indicating low resistance to flow suitable for applications.

Synthesis

Industrial Methods

Mesitylene is primarily produced on an industrial scale through the transalkylation of C₈ aromatics, such as mixed or , over zeolite-based catalysts at temperatures ranging from 300 to 400 °C. This process involves the redistribution of alkyl groups to form 1,3,5-trimethylbenzene (mesitylene) alongside other from the C₈ feedstream, often integrated into operations for BTX (, , ) production to maximize yield from heavy aromatic fractions. Zeolites like H-ZSM-5 or mordenite provide selectivity and acidity essential for high conversion rates and selectivity toward the symmetric mesitylene . Historically, mesitylene has been isolated from via of the middle oil fraction, where it comprises approximately 0.5-2% of the distillate alongside other isomers and naphthalenes. However, this source has declined significantly with the global shift from coal-based to petroleum-derived feedstocks, as modern refineries favor integrated aromatic complexes over traditional processing. An alternative industrial route involves the trimerization of acetone in the presence of as a catalyst, proceeding via acid-catalyzed aldol condensations and dehydrations to yield mesitylene, though this method is now less prevalent due to higher costs and environmental concerns compared to routes. The is projected to reach approximately USD 245 million by 2032, reflecting a (CAGR) of 4.5%, with significant contributions from applications in solvents and resins. Purification of crude mesitylene streams typically employs to achieve >99% purity suitable for industrial applications, supplemented by adsorption processes using molecular sieves or clays to remove impurities like other isomers and olefins.

Laboratory Methods

One of the classic laboratory methods for synthesizing mesitylene involves the acid-catalyzed trimerization of acetone using concentrated . In this procedure, technical acetone (4600 g, 79 moles) is placed in a large vessel and cooled to 0–10 °C using an ice-salt bath, while commercial concentrated (4160 cc) is added slowly over 5–10 hours with vigorous stirring to control the . The mixture is then stirred for an additional 3–4 hours at the same temperature and allowed to stand at for 18–24 hours, during which the temperature rises to 40–50 °C. The product is isolated by , yielding 430–600 g of mesitylene (13–15% theoretical yield, average 510 g). Mesitylene can also be obtained from mesityl oxide, the aldol condensation dimer of acetone, through further acid-catalyzed condensation with additional acetone or alternative alkylation routes in bench-scale setups. For example, mesityl oxide undergoes subsequent dehydration and cyclization steps under acidic conditions to form the aromatic ring, often as part of one-pot processes from acetone. Reduction pathways, such as hydrogenolysis over metal catalysts, have been explored but typically require high pressures and are less common for direct conversion to mesitylene. A modern laboratory approach employs catalytic of with over solid acid catalysts like HZSM-5 , enabling selective addition of a at the 5-position to yield mesitylene. This method operates under controlled gas-phase conditions at elevated temperatures (around 300–400 °C) and , offering improved selectivity in small-scale reactors compared to traditional routes. Regardless of the synthesis route, purification of mesitylene typically involves washing the crude distillate with solution and to remove acidic impurities, followed by drying and at reduced pressure (e.g., 10–20 mmHg) to collect the fraction boiling at 163–167 °C, achieving purity greater than 99%. Laboratory syntheses of mesitylene, particularly the sulfuric acid-mediated trimerization, are highly exothermic and generate significant fumes; reactions must be performed in a well-ventilated fume hood with appropriate cooling to prevent runaway conditions. Detailed safety protocols, including handling of corrosive acids, are outlined in the dedicated Safety section.

Chemical Reactivity

Electrophilic Aromatic Substitution

Mesitylene, or 1,3,5-trimethylbenzene, displays significantly enhanced reactivity toward electrophilic aromatic substitution (EAS) compared to benzene owing to its three methyl substituents, which act as strong electron-donating groups that increase the electron density across the aromatic ring. These groups are ortho-para directors, facilitating electrophilic attack at the available ring positions. The overall rate of EAS reactions for mesitylene is approximately 300 times faster than for benzene in nitration, reflecting the cumulative activating effect of the methyl groups. Despite this activation, the steric bulk of the s at the 1, 3, and 5 positions creates significant hindrance, impeding direct approach of the to these sites and often leading to ipso substitution—where attack occurs at a carbon bearing a , potentially resulting in rearrangement—or diversion to side-chain attack under milder conditions. This steric effect modulates the otherwise high reactivity, making certain EAS reactions more challenging than expected for a trialkyl-substituted arene. Under some conditions, competing oxidation of the s can occur alongside ring substitution. Halogenation exemplifies these dynamics: bromination with in carbon tetrachloride at 10–15°C affords mesityl bromide (1-bromo-2,4,6-trimethylbenzene, \ceC6H2(CH3)3Br\ce{C6H2(CH3)3Br}) in 79–82% yield, proceeding via electrophilic attack at one of the equivalent ring hydrogens. Chlorination follows a comparable pathway, yielding the chloro analog under similar mild conditions with gas or hypochlorite sources. Nitration typically introduces one nitro group under standard conditions with in acetic anhydride, but achieving trinitration requires forcing conditions, such as concentrated sulfuric and nitric acids at elevated temperatures, to yield 2,4,6-trinitromesitylene due to deactivation by the initial nitro substituent. Friedel-Crafts acylation is constrained by steric hindrance, rendering traditional alkylation ineffective, but acylation succeeds with acyl chlorides or anhydrides and Lewis acids like \ceAlCl3\ce{AlCl3}, or alternatively with carboxylic acids and triflate catalysts in solventless setups, producing mesityl ketones such as 2,4,6-trimethylacetophenone.

Oxidation and Other Reactions

Mesitylene undergoes vigorous oxidation under strong conditions, such as treatment with aqueous (KMnO₄), to afford (1,3,5-benzenetricarboxylic acid) in good yields. This reaction cleaves all three methyl side chains to groups, leveraging the stability of the aromatic ring. Similarly, can effect complete side-chain oxidation to the same product, though it is less commonly employed due to environmental concerns associated with waste. Industrial variants often use air as the oxidant in the presence of cobalt-manganese-bromide catalysts in acetic acid, achieving high selectivity to under controlled temperatures and pressures. Under milder conditions, mesitylene can be selectively oxidized to mesitol (2,4,6-trimethylphenol), where one is converted to a hydroxyl functionality. This transformation is achieved using in a mixture of acetic acid, , and , yielding mesitol with 57–69% selectivity based on converted mesitylene. Catalytic air oxidation systems, typically involving metal salts, have also been explored for this phenol formation, though they require precise control to avoid over-oxidation to quinones or further degradation products. Selective side-chain oxidation of mesitylene targets the benzylic positions to produce aldehydes, such as 3,5-dimethylbenzaldehyde, without affecting the ring or other methyl groups. (SeO₂) serves as a classic reagent for this benzylic dehydrogenation, promoting mono-oxidation due to the steric hindrance of the ortho methyl substituents. Modern catalytic approaches enhance selectivity and sustainability; for instance, (III) complexes with Phebox ligands, using as a terminal oxidant, convert mesitylene to 3,5-dimethylbenzaldehyde at 130 °C. N-bromosuccinimide (NBS) can facilitate benzylic bromination as a precursor step, which upon or further treatment yields the , though direct oxidation protocols are preferred for efficiency. Hydrogenation of mesitylene reduces the aromatic ring to 1,3,5-trimethylcyclohexane, typically employing (Pd/C) as the catalyst under gas at elevated temperatures and pressures. This reaction proceeds stereoselectively, favoring the cis due to the symmetric substitution pattern. Alternative catalysts like on alumina achieve similar outcomes in gas-phase processes at 418–523 , with kinetics influenced by partial . Photochemical reactions of mesitylene under UV enable C–H , often leading to oxidative dimerization or coupling products via radical intermediates. In the presence of photosensitizers or initiators like O(³P) atoms, UV light promotes selective benzylic oxidation or addition pathways. Recent advancements include photo-catalytic systems using , which facilitate the conversion of mesitylene to 3,5-dimethylbenzaldehyde under visible/UV light, offering a sustainable route for synthesis with high and minimal waste. These methods address environmental concerns by avoiding stoichiometric oxidants, aligning with principles for post-2020 applications in pharmaceutical intermediates.

Applications

Solvent and Industrial Uses

Mesitylene serves as a versatile in industrial applications, particularly in the formulation of resins, paints, and polymers, owing to its high of 165 °C and strong solvency for non-polar compounds. Its chemical stability and low reactivity enable effective dissolution of gums, , and other materials, facilitating smooth application and durability in coatings and varnishes. This makes it a preferred choice over more volatile alternatives in processes requiring controlled rates. In addition to its solvent role, mesitylene acts as a critical precursor in the synthesis of 2,4,6-trimethylaniline (mesidine), which is further utilized in producing dyes and pigments for various industrial colorants. A significant portion of global mesitylene consumption is allocated to solvent uses across these sectors. Market growth for mesitylene from 2020 to 2025 has been propelled by rising demand in electronics manufacturing, where high-purity grades support advanced polymer formulations, and by advancements in sustainable chemistry that favor its eco-friendly profile relative to more hazardous solvents. In regions like India, expanding resin production for paints and coatings has further driven adoption, with the local market valued at approximately USD 699 million in 2025 and projected to grow at a 3% CAGR through 2031. Mesitylene's relatively low toxicity, with an LD50 greater than 5,000 mg/kg in rats, supports its preference in these applications.

Niche and Specialized Applications

Mesitylene serves as an in () due to its distinct, sharp singlet peaks at approximately 6.8 ppm for the aromatic protons and 2.3 ppm for the methyl protons, which rarely overlap with signals from other organic compounds. This property makes it particularly useful for quantitative analysis in reaction monitoring and product yield determination in synthetic chemistry. In manufacturing, it functions as a in strippers, facilitating the removal of cured isoprene-based resists in patterning without damaging underlying layers. As a precursor in , mesitylene coordinates to transition metals such as , , and in complexes like (η⁶-mesitylene)M(CO)₃, which catalyze the polymerization of substituted acetylenes to yield polyacetylenes with molecular weights up to 12,000. These catalysts enable controlled polymer synthesis under mild conditions, contributing to for and . Mesitylene also finds niche roles as a calibration standard in for analyzing volatile organic compounds, particularly aromatic hydrocarbons in environmental and fuel samples, due to its well-defined retention time and stability. In fragrance synthesis, it is employed as a and for fragrance agents, aiding in the formulation of stable, aromatic compositions without altering scent profiles.

Mesityl Group

Definition

The mesityl group, abbreviated as Mes, is the aryl substituent known as 2,4,6-trimethylphenyl, with the molecular formula C₆H₂(CH₃)₃⁻. This group features a ring substituted with methyl groups at the 2, 4, and 6 positions relative to the point of attachment. It is commonly notated as Mes or (2,4,6-Me₃C₆H₂)⁻ in chemical literature. The mesityl group is derived from mesitylene (1,3,5-trimethylbenzene) through or substitution at the 1-position of the aromatic ring. Its three ortho-methyl substituents create substantial steric bulk, enabling the group to shield reactive sites and provide steric protection in molecular constructs. The name mesityl originates from mesitylene, a frequently used in .

Applications in Synthesis

The mesityl group, with its bulky ortho-methyl substituents, imparts significant steric hindrance that is particularly valuable in ligand design for catalysts, enhancing selectivity and stability in cross-coupling reactions. For instance, mesityl-substituted phosphines, such as 2-mesitylindenyl dicyclohexylphosphine, serve as effective s in -catalyzed Buchwald-Hartwig aminations of aryl chlorides, where the steric bulk promotes while suppressing unwanted side reactions. Similarly, N-mesityl groups in N-heterocyclic carbenes (NHCs) provide remote steric control in systems, accelerating key steps like the formation of Breslow intermediates in related , though their role extends to Pd-mediated couplings by tuning the catalyst's . In synthesis, the mesityl group functions as a steric protecting moiety at meso-positions, shielding the from aggregation and facilitating regioselective functionalization without scrambling of substituents. This is exemplified in the preparation of trans-A₂B₂-mesoaryl , where mesityl incorporation during prevents undesired rearrangements and enables high-yield access to intermediates for further derivatization, such as hydroxyl or methoxy groups. The bulky nature of mesityl also stabilizes the core during oxidative cyclization, allowing for the synthesis of otherwise labile structures used in optoelectronic applications. Frustrated Lewis pairs (FLPs) incorporating mesityl groups have emerged as metal-free catalysts for , leveraging the steric encumbrance to prevent classical formation and enable cooperative of H₂. Early examples include Mes₃P/B(C₆F₅)₃ and Mes₂BH/P(tBu)₃ systems, which heterolytically cleave dihydrogen to form active hydridoborate or species capable of reducing imines, alkenes, and carbonyls under mild conditions. The mesityl substituents on or enhance the FLP's lifetime and selectivity, as seen in enantioselective variants for of ketones by tuning the chiral environment around the reactive sites. Recent advancements (2020–2025) highlight mesityl ligands in sustainable for CO₂ reduction, particularly in bioinspired porphyrin-based systems where mesityl groups on the provide steric protection to the metal center. Iron porphyrins bearing mesityl substituents, such as Py₂XPFe, facilitate electrochemical CO₂ reduction to CO with high turnover frequencies (up to 2.1 × 10⁸ s⁻¹) by stabilizing key intermediates like CO-bound species, while the bulk mitigates dimerization side products. In 2024, mesityl groups were employed in the synthesis of dibenzo-fused perioctacene to provide steric protection at radical sites, preventing aggregation in advanced . These designs draw from natural enzymes, emphasizing mesityl's role in promoting bimetallic cooperation for efficient, low-overpotential conversion. Exemplary applications include Mes₃B as a tunable Lewis acid in FLP chemistry, where its steric profile supports reversible H₂ activation and small-molecule binding, such as in the formation of sandwich complexes that enhance anion recognition for sensing applications. In cross-coupling, mesityl-palladium complexes, derived from mesitylcopper reagents, enable efficient arylation of aryl iodides with electron-withdrawing or donating groups, proceeding via under phase-transfer conditions to yield biaryls in good yields. These examples underscore the mesityl group's versatility in promoting sterically controlled reactivity across synthetic methodologies.

History

Early Discovery

Mesitylene was first prepared in 1837 by Irish chemist Robert Kane through the acid-catalyzed condensation of acetone with concentrated , resulting in a distillate that he named "mesitylene," derived from the Greek word for mediator, as he believed it represented a polymeric form of acetone. Kane detailed this synthesis in his publication on combinations derived from pyroacetic spirit (acetone), marking the initial isolation of the compound as a distinct . In the mid-19th century, subsequent investigations by chemists contributed to understanding mesitylene's properties and its relation to aromatic hydrocarbons, building on Kane's work amid growing interest in . These early studies helped establish mesitylene's stability and characteristics, distinguishing it from aliphatic compounds. Mesitylene was also identified among the components of distillates during the 1860s, as chemists analyzed the complex mixtures from industrial coal processing, recognizing it as a naturally occurring . A key advancement came in 1874 when German chemist Albert Ladenburg elucidated mesitylene's structure as 1,3,5-trimethylbenzene through oxidative degradation to trimesic acid (1,3,5-benzenetricarboxylic acid), providing conclusive evidence of its symmetric aromatic framework despite initial assumptions of alternative ring geometries like prismane.

Development and Commercialization

Following World War I, the production of mesitylene shifted from traditional coal tar sources to petrochemical feedstocks derived from petroleum refining, driven by advancements in catalytic processes and the growing availability of crude oil derivatives. This transition allowed for more scalable and cost-effective synthesis through methods like catalytic reforming of naphtha, replacing labor-intensive coal coking operations. In the and , industrial transalkylation processes emerged as a key method for mesitylene production, converting C9+ aromatic fractions from streams into valuable trimethylbenzenes. Companies such as Universal Oil Products (UOP) and Exxon pioneered these technologies, integrating transalkylation units into aromatic complexes to enhance yields from and heavier aromatics, particularly to meet demands for high-octane fuels and solvents during postwar economic expansion. Building on early laboratory methods like Kane's, these processes emphasized acid-catalyzed alkyl group transfers under controlled conditions. A significant milestone in the 1980s was the adoption of zeolite-based catalysts, such as , which improved selectivity and yields in transalkylation and reactions for mesitylene. These shape-selective catalysts minimized side products and operated at lower temperatures, boosting efficiency in plants and addressing limitations of earlier alumina-based systems. Since 2000, mesitylene production has seen robust growth in , fueled by rapid industrialization in and , where new refinery capacities and aromatic complexes have expanded output to support regional chemical . The global market, driven by demand in for high-purity solvents and emerging routes using renewable feedstocks, was valued at approximately USD 163 million in 2023 and is projected to reach USD 245 million by 2032, reflecting a (CAGR) of 4.5% (as of 2024 estimates). Recent developments as of 2025 include exploratory bio-based production methods from and waste via and catalytic processes, promoting . accounts for a significant portion of production and consumption due to sector growth and sustainable production initiatives.

Safety and Environmental Impact

Health Hazards and Toxicity

Mesitylene (1,3,5-trimethylbenzene) acts primarily as an irritant upon acute exposure, affecting the skin, eyes, and , with symptoms including redness, tearing, and coughing at concentrations above 25 ppm. High-level can lead to (CNS) depression, manifesting as dizziness, headache, nausea, and drowsiness, particularly at levels exceeding 1,000 ppm in animal models where narcosis and were observed. Human studies report no or CNS effects at 25-30 ppm over 2-8 hours, but vertigo and have been noted occupationally at 10-60 ppm. Oral is low in , with an LD50 greater than 8,400 mg/kg in rats, though it may cause gastrointestinal and aspiration risk due to its low viscosity. Chronic exposure to mesitylene poses risks of liver and damage, as evidenced by increased organ weights and altered serum levels (e.g., elevated and ) in rats administered 600 mg/kg-day orally for 90 days. Neurobehavioral effects, such as learning and memory deficits, occur in rats at concentrations of 25 ppm or higher over subchronic periods. Developmental includes reduced fetal weight and increased resorptions in rats exposed to 6.9 ppm via during , though no maternal was seen at 100 ppm. Hematological changes like hyperchromic and respiratory issues resembling chronic have been reported in humans with prolonged low-level exposure. As a , mesitylene contributes to indoor , potentially exacerbating these effects in occupational settings. Occupational exposure limits for mesitylene are established to prevent these effects: the NIOSH (REL) is a time-weighted average () of 25 ppm (125 mg/m³) over 10 hours, based on CNS and hematological risks. OSHA has no specific (PEL) for mesitylene, though mixed isomers are regulated at 25 ppm in construction and maritime sectors; analogous aromatic hydrocarbons like have a PEL of 100 ppm. The immediately dangerous to life or health (IDLH) value is not defined by NIOSH. LC50 in rats is 18,000 mg/m³ (approximately 3,000 ppm) over 4 hours, indicating relatively low acute lethality compared to more toxic solvents. Safe handling requires (PPE), including gloves, goggles, and respirators in poorly ventilated areas, due to mesitylene's flammability ( 50°C) and irritant properties. Consumption of alcoholic beverages can enhance its harmful CNS effects, as seen with similar alkylbenzenes, necessitating avoidance of alcohol during exposure. like local exhaust ventilation are recommended to maintain levels below 25 ppm.

Ecological Effects

Mesitylene, or 1,3,5-trimethylbenzene, is emitted as a (VOC) primarily from industrial solvent use, vehicle evaporation, and incomplete combustion processes in urban areas. These emissions contribute significantly to the formation of and secondary organic aerosols through photochemical reactions with hydroxyl radicals and oxides in the atmosphere. As a major urban air pollutant, mesitylene's reactivity enhances tropospheric production, exacerbating formation in populated regions. In aquatic environments, mesitylene exhibits high to , with an LC50 of 3.48 mg/L for fathead minnows (Pimephales promelas) over 96 hours. It is classified under the EU CLP regulation as Aquatic Chronic 2 (H411), indicating toxic effects with long-lasting consequences for aquatic ecosystems. Freshwater species, such as and , show heightened sensitivity compared to marine organisms, with EC50 values around 3 mg/L for algal growth inhibition. Mesitylene demonstrates moderate bioaccumulation potential in , with a bioconcentration factor (BCF) of approximately 161 in fathead minnows. It undergoes degradation primarily through microbial oxidation in , limiting long-term accumulation in biota. In and atmospheric compartments, mesitylene evaporates rapidly due to its high (1.2 mmHg at 20°C), reducing persistence in surface layers. Atmospheric photodegradation via reaction with hydroxyl radicals occurs with a of 11-12 hours, preventing widespread aerial transport. Its low solubility (48.2 mg/L at 25 °C) and strong adsorption to (Koc ≈ 1,800) limit leaching into , though spills can cause localized contamination. Regulatory measures address mesitylene's ecological risks through the EU REACH framework, where it is registered and classified for environmental hazards, with emissions controlled under the VOC Directive (2010/75/EU) to mitigate air quality impacts. In the United States, the EPA regulates mesitylene as a VOC under the Clean Air Act, imposing controls on industrial emissions to reduce contributions to ozone non-attainment areas.

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