4-Methyl-1,3-benzenediol
[CAS 496-73-1]

Identification

• Classification: Chemical reagent >> Organic reagent >> Phenols
• Name: 4-Methyl-1,3-benzenediol
• Synonyms: 1,3-Dihydroxy-4-methylbenzene; 2,4-Dihydroxyphenylmethane; 2,4-Dihydroxytoluene; 2,4-Toluenediol; 4-Methylresorcinol; 4-Methyl-1,3-dihydroxybenzene
• Molecular Formula: C₇H₈O₂
• Molecular Weight: 124.14
• CAS Registry Number: 496-73-1
• EC Number: 207-827-8
• SMILES: CC1=C(C=C(C=C1)O)O

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Melting point: 104 - 108 °C (Expl.)
• Boiling point: 264.0 °C 760 mmHg (Calc.)^*
• Flash point: 130.1±13.6 °C (Calc.)^*
• Index of refraction: 1.595 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335

chemBlink Chemical Story

4-Methyl-1,3-benzenediol, CAS 496-73-1, is a methyl-substituted derivative of resorcinol and is also known as 4-methylresorcinol or 2,4-dihydroxytoluene. Its molecular formula is C₇H₈O₂ and its molecular weight is 124.14. The molecule contains two phenolic hydroxyl groups in the meta relationship and a methyl group adjacent to one of them.

At first glance, the structure differs only slightly from resorcinol. Resorcinol is benzene-1,3-diol; 4-methylresorcinol simply adds CH₃ to the aromatic ring. Yet substituting even one hydrogen on an aromatic molecule changes its symmetry, electron distribution, steric environment, and the relative reactivity of the remaining ring positions.

The two hydroxyl groups are especially important. Phenolic hydroxyl groups donate electron density into an aromatic ring through resonance and strongly influence electrophilic aromatic substitution. A methyl group is also electron donating, although by a different mechanism. With three substituents already present, the molecule therefore contains several competing electronic and steric influences that determine where additional chemistry can occur.

This makes 4-methylresorcinol a useful organic synthetic building block. New substituents can be introduced onto the electron-rich aromatic framework, while the hydroxyl groups themselves can undergo reactions such as etherification or esterification. The compound has consequently appeared as an intermediate in the preparation of more elaborate aromatic molecules.

One experimentally documented example comes from research on the biomimetic synthesis of natural products involving ortho-quinone methides. Researchers used commercially available 4-methylresorcinol as a starting material and introduced an acetyl group through Friedel-Crafts acylation. Under optimized conditions using acetic acid and boron trifluoride etherate, 2-acetyl-4-methylresorcinol was obtained in a reported 71% yield.

This experiment illustrates how the substitution pattern already present in 4-methylresorcinol directs later molecular construction. The two hydroxyl groups make the aromatic ring electron rich, but the existing methyl group and hydroxyl groups also distinguish the available carbon positions from one another. Synthetic chemists can exploit these differences to build increasingly substituted aromatic systems.

There is another intriguing side to the molecule: biology can also recognize its substitution pattern.

Tyrosinase is a copper-containing enzyme best known for its central role in melanin formation. It catalyzes oxidation reactions involving phenolic substrates and has consequently become an important target in research on pigmentation and enzymatic browning.

Resorcinol derivatives have been investigated in this context, including 4-methylresorcinol. They have sometimes been described as tyrosinase inhibitors, suggesting that they reduce enzyme activity by interfering with catalysis.

Closer mechanistic investigation, however, revealed a more complicated picture. A study examining the action of tyrosinase on resorcinols concluded that compounds including 4-methylresorcinol can behave as alternative substrates of the enzyme rather than functioning only as conventional inhibitors.

This distinction matters. An inhibitor and a substrate interact with an enzyme in fundamentally different ways. An inhibitor reduces catalytic activity, whereas a substrate enters the catalytic process and is chemically transformed. A compound may nevertheless appear to inhibit a normal reaction under some experimental conditions if it competes with the usual substrate for the enzyme.

The example provides a useful lesson in biochemical terminology. Observing that a compound reduces formation of a particular product does not automatically reveal the molecular mechanism responsible. Kinetic experiments and identification of reaction products may be needed to determine whether the compound blocks the enzyme, competes for its active site, or is itself processed by the enzyme.

4-Methylresorcinol is also interesting from the perspective of biocatalysis. Researchers studying toluene-o-xylene monooxygenase from Pseudomonas stutzeri OX1 demonstrated that protein engineering could alter the regioselectivity of this bacterial enzyme system. Mutated forms of the enzyme were able to produce 4-methylresorcinol by hydroxylating cresol substrates.

That experiment reverses the usual way we think about organic synthesis. Instead of choosing reagents to decide where a hydroxyl group should be installed on an aromatic ring, researchers changed amino acids inside an enzyme so that the protein itself favored a different position of oxidation.

Regioselectivity is one of the recurring challenges of aromatic chemistry. Several carbon atoms in an aromatic molecule may appear chemically similar, yet the desired product often requires reaction at only one of them. Enzymes achieve such selectivity by holding substrates in specific orientations inside three-dimensional active sites.

Protein engineering makes that selectivity adjustable. Changing selected amino acids can alter the size, shape, or chemical environment of the active site and therefore change how a substrate approaches the catalytic center. The product distribution can change even though the starting material and overall type of reaction remain the same.

4-Methylresorcinol therefore connects conventional organic chemistry with enzymatic chemistry in an unusually compact molecule. In a laboratory flask, its hydroxyl and methyl substituents control the behavior of an electron-rich aromatic ring. Inside an enzyme, the same molecular shape becomes something that a protein must recognize and orient before reaction occurs.

The compound is a white to light-colored solid under ordinary conditions. Reference suppliers report a melting range around 104-108 °C. Its apparently simple structure conceals the characteristic reactivity of phenols and the subtle positional effects that arise when several substituents occupy the same aromatic ring.

The lesson of 4-methylresorcinol is therefore not simply that it is resorcinol with an extra methyl group. In aromatic chemistry, position matters. Moving or adding even a small substituent changes which carbon atoms are equivalent, which positions are accessible, and how electrons are distributed around the ring.

And in biological chemistry, position can matter even more. An enzyme does not merely count functional groups; it recognizes a three-dimensional arrangement. A methyl group containing only one carbon can therefore help determine how an entire molecule fits into an active site and what chemistry follows.

References

1. NIST Chemistry WebBook. 4-Methylresorcinol, CAS 496-73-1. Molecular formula C₇H₈O₂; molecular weight 124.1372.
https://webbook.nist.gov/cgi/cbook.cgi?ID=C496731

2. PubChem. 1,3-Benzenediol, 4-methyl-, CID 10333.
https://pubchem.ncbi.nlm.nih.gov/compound/10333

3. Garcia-Molina, M. M. et al. (2016). "Characterization of the action of tyrosinase on resorcinols." Bioorganic & Medicinal Chemistry. Study of resorcinol derivatives including 4-methylresorcinol as substrates of tyrosinase.

4. Vardar, G.; Wood, T. K. (2004). "Protein Engineering of Toluene-o-Xylene Monooxygenase from Pseudomonas stutzeri OX1 for Synthesizing 4-Methylresorcinol, Methylhydroquinone, and Pyrogallol." Applied and Environmental Microbiology, 70, 3253-3262.
https://pmc.ncbi.nlm.nih.gov/articles/PMC427803/

5. Studies of 4-methylresorcinol as a starting material for substituted resorcinols and ortho-quinone-methide precursors.