1,3,5-Trimethoxybenzene (621-23-8) Physical and Chemical Properties
1,3,5-Trimethoxybenzene
A trimethoxy-substituted aromatic ether employed as a reagent and intermediate in fragrance ingredient synthesis, fine-chemical research, and analytical standard preparation.
| CAS Number | 621-23-8 |
| Family | Trimethoxybenzenes (aromatic ethers) |
| Typical Form | White crystalline solid |
| Common Grades | EP, JP, Reagent Grade |
1,3,5-Trimethoxybenzene is an aromatic ether of the trimethoxybenzene family: a benzene core symmetrically substituted at the 1, 3 and 5 positions with methoxy groups. Its molecular formula is \(\ce{C9H12O3}\), giving a molecular weight of 168.19. The three methoxy substituents confer an electron-rich aromatic ring (strongly activating, ortho/para directing for electrophilic aromatic substitution at the 2,4,6 positions) and impart moderate polarity relative to unsubstituted benzene while maintaining overall lipophilicity acceptable for organic-solvent solubility.
Structurally the compound is C3-symmetric (1,3,5-substitution pattern) with three ether linkages that act as weak hydrogen-bond acceptors (hydrogen-bond donor count = 0; hydrogen-bond acceptor count = 3). The low topological polar surface area (TPSA = 27.7) together with an XLogP3 value of 2 indicates limited aqueous solubility and appreciable partitioning into organic phases. The ether functions are generally stable under neutral conditions but can be cleaved under strong acidic or reductive/demethylating conditions; the electron-rich ring is susceptible to electrophilic oxidation under vigorous oxidative conditions.
The substance is encountered in fragrance and flavor contexts and also appears as a biological metabolite and analytical marker in biological studies. It is supplied commercially in several pharmacopoeial and reagent grades. Common commercial grades reported for this substance include: EP, JP, Reagent Grade.
Basic Physical Properties
1,3,5-Trimethoxybenzene is a solid under ambient laboratory conditions and is described as a white crystalline solid.
Density
No experimentally established value for this property is available in the current data context.
Melting Point
No experimentally established value for this property is available in the current data context.
Boiling Point
No experimentally established value for this property is available in the current data context.
Vapor Pressure
No experimentally established value for this property is available in the current data context.
Flash Point
No experimentally established value for this property is available in the current data context.
Chemical Properties
Solubility and Phase Behavior
As an aromatic trimethyl ether, 1,3,5-trimethoxybenzene is poorly soluble in water and readily soluble in common organic solvents (e.g., ethers, dichloromethane, chloroform, ethanol). The combination of moderate lipophilicity (XLogP3 = 2) and low TPSA (27.7) drives partitioning into nonpolar and moderately polar organic phases; solid-state handling will predominate in bulk and analytical contexts where it is used as a crystalline reagent or standard.
Reactivity and Stability
The three methoxy groups are electron-donating and stabilize positive charge in the aromatic system; they make the ring more reactive toward electrophilic aromatic substitution and more vulnerable to oxidative attack under harsh conditions. The methoxy O–CH3 bonds are relatively stable to neutral hydrolysis but can undergo demethylation under strong acidic, nucleophilic or oxidative conditions (e.g., strong Lewis/Brønsted acids or catalytic oxidative demethylation). Under normal storage and handling (cool, dry, inert or ambient air), the compound is chemically stable; exposures to strong oxidants, strong acids or elevated temperatures should be minimized to avoid degradation.
Thermodynamic Data
No experimentally established value for this property is available in the current data context.
Standard Enthalpies and Heat Capacity
No experimentally established value for this property is available in the current data context.
Molecular Parameters
Molecular Weight and Formula
- Molecular formula: \(\ce{C9H12O3}\)
- Molecular weight: 168.19
- Exact mass / Monoisotopic mass: 168.078644241
LogP and Polarity
- XLogP3: 2
- Topological polar surface area (TPSA): 27.7
- Hydrogen-bond donor count: 0
- Hydrogen-bond acceptor count: 3
- Rotatable bond count: 3
These parameters indicate a molecule with low polar surface area and moderate lipophilicity, consistent with low aqueous solubility and good solubility in organic media.
Structural Features
The structure consists of a benzene ring bearing three methoxy substituents in the 1,3,5 positions (symmetrical arrangement). The methoxy groups are electron-donating through resonance and inductive effects, increasing electron density on the ring and modifying reactivity: enhanced rates of electrophilic substitution at the remaining ring positions and increased susceptibility to oxidative pathways. The absence of hydrogen-bond donors and the three ether oxygens create modest polarity limited to acceptor interactions; steric hindrance around the ring is low, and the molecule is conformationally simple.
Identifiers and Synonyms
Registry Numbers and Codes
- CAS number: 621-23-8
- EC number: 210-673-4
- UNII: 00VJI3VG3D
- ChEBI: CHEBI:31038
- ChEMBL: CHEMBL1605492
- DrugBank: DB15875
- DSSTox Substance ID: DTXSID0045963
- HMDB: HMDB0059963
- KEGG ID: D01792
- NSC Number: 90060
- InChI:
InChI=1S/C9H12O3/c1-10-7-4-8(11-2)6-9(5-7)12-3/h4-6H,1-3H3 - InChIKey:
LKUDPHPHKOZXCD-UHFFFAOYSA-N - SMILES:
COC1=CC(=CC(=C1)OC)OC
Synonyms and Structural Names
Reported synonyms include (selected from supplier and depositor names):
- 1,3,5-trimethoxybenzene
- trimethylphloroglucinol
- Phloroglucinol trimethyl ether
- Benzene, 1,3,5-trimethoxy-
- O,O,O-1,3,5-Trimethylresorcinol
(Additional alternative names and vendor descriptors are recorded in supplier specifications.)
Industrial and Commercial Applications
Representative Uses and Industry Sectors
1,3,5-Trimethoxybenzene is used as a fragrance ingredient and flavor/fragrance intermediate in olfactory formulations, consistent with its inclusion in fragrance-ingredient listings. It is also encountered as a standard in analytical chemistry (e.g., GC-MS reference; quantitative NMR standards) and as a reagent or building block in organic synthesis. The compound has been detected as a biomarker and human xenobiotic metabolite in biological studies, indicating occurrence in metabolomic contexts.
The substance is noted as commercially active in chemical inventories and is supplied in multiple analytical and reagent grades suitable for laboratory and industrial use.
Role in Synthesis or Formulations
Functionally, 1,3,5-trimethoxybenzene serves as an electron-rich aromatic substrate in electrophilic aromatic substitution, cross-coupling transformations, and as an intermediate in multi-step syntheses where protected phenolic motifs are required. In formulation work it contributes olfactory characteristics and can act as a solvent-soluble aromatic component for fragrance blends. Selection for synthetic or formulation work is driven by its symmetry, reactivity profile, and solvent compatibility.
Safety and Handling Overview
Acute and Occupational Toxicity
Available hazard classification information indicates acute oral toxicity and eye irritation potential: hazard codes reported include H302 (harmful if swallowed) and H319 (causes serious eye irritation). Aggregated classification summaries cite Acute Tox. 4 and Eye Irrit. 2A categories in notified classifications. As an irritant, contact with eyes and ingestion should be avoided; standard industrial hygiene controls apply.
Storage and Handling Considerations
Store in a cool, dry, well‑ventilated area away from strong oxidizers and strong acids. Use appropriate personal protective equipment (chemical-resistant gloves, safety goggles, lab coat) and local exhaust ventilation for dust or powder handling. Avoid ingestion and minimize generation of dust; handle under inert atmosphere if prolonged high-temperature or strongly oxidative operations are performed. For detailed hazard, transport and regulatory information, users should refer to the product-specific Safety Data Sheet (SDS) and local legislation.
Acceptable commercial supply grades include EP, JP and Reagent Grade; grade selection should be based on intended use (analytical standard, synthesis reagent, formulation ingredient) and required purity/traceability attributes.
