Tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), and 3-methyltetrahydrofuran (3-MeTHF) sit at the heart of one of organic chemistry's most consequential ether-solvent decisions. They look almost identical on paper - five-membered cyclic ethers, similar molecular weights, similar polarities - but a single methyl group's position changes water miscibility, peroxide stability, cost, and supply availability. This guide compares all three side by side and provides a decision framework for choosing the right one.

1. Structural Differences: Where the Methyl Group Sits

All three solvents share the same backbone: a saturated five-membered ring containing four carbon atoms and one oxygen atom - the tetrahydrofuran (oxolane) framework. The difference lies in the position and presence of a methyl substituent.

2-MeTHF and 3-MeTHF are structural isomers - same molecular formula (C₅H₁₀O), same molecular weight (86.13 g/mol), but different connectivity. The methyl group on 2-MeTHF sits at the carbon directly bonded to oxygen, where it sterically shields the ether oxygen from solvent and reactive species. On 3-MeTHF, the methyl group sits one carbon further away, leaving the oxygen more exposed and behaving electronically more like THF.

2. Side-by-Side Property Comparison

The table below collects the most decision-relevant properties of all three solvents. For deeper engineering interpretation of each value, see our 2-MeTHF physical & chemical properties article.

A few patterns jump out from this table. Boiling points climb in the order THF < 2-MeTHF < 3-MeTHF, reflecting the contribution of the methyl substituent to molecular weight and van der Waals attraction. Density tracks the opposite direction: THF is densest, 2-MeTHF lowest, with 3-MeTHF in between. Water miscibility is the largest qualitative break - THF is fully miscible while both methylated isomers separate.

3. Water Miscibility Behavior

For most industrial process chemistry, water miscibility is the single most consequential difference between the three solvents.

3.1 THF: fully miscible

THF is miscible with water in all proportions. This is occasionally useful - for example, in homogeneous reaction systems that require water as a reagent or for hydrogen-bonding interactions with substrate. More often, full miscibility is a liability: aqueous workup of a THF reaction requires either salt addition to break miscibility, multiple extractions to recover product, or evaporative removal of dissolved THF from the aqueous waste.

3.2 2-MeTHF: limited miscibility

2-MeTHF dissolves about 14 grams of water per 100 mL, with a similar reverse solubility. The methyl group adjacent to oxygen sterically blocks deeper hydrogen-bonding penetration, creating a clean phase boundary above this concentration limit. The result is single-pass aqueous workup, simpler waste handling, and faster overall process throughput.

3.3 3-MeTHF: similar to 2-MeTHF but less data

3-MeTHF likewise has limited water miscibility, similar in magnitude to 2-MeTHF. Less published data exists because 3-MeTHF is a specialty solvent rather than a high-volume industrial chemical, but the practical extraction behavior is comparable.

4. Peroxide Formation Comparison

All three cyclic ethers can form organic peroxides on prolonged exposure to air, light, and trace metal contaminants. The rate of peroxide accumulation depends on the chemistry of hydrogen abstraction at the carbon adjacent to oxygen - the alpha-C-H bond.

In THF, both alpha carbons are unsubstituted and equally susceptible to autoxidation. In 2-MeTHF, one alpha carbon carries a methyl group, sterically and electronically slowing peroxide formation at that position. In 3-MeTHF, the methyl group is on the beta carbon and does not directly shield either alpha position, giving 3-MeTHF a peroxide tendency closer to THF than to 2-MeTHF.

In practical terms, 2-MeTHF stored under recommended conditions (BHT-stabilized, sealed, dark, cool) accumulates measurable peroxides more slowly than THF under the same conditions. This translates into longer shelf life and lower handling risk - particularly important for users who run intermittent or low-volume processes where solvent inventory may sit for months between uses. See our handling, storage & safety article for testing protocols and storage best practices.

5. Cost & Supply Availability

Cost and supply availability differ dramatically across the three solvents, in ways that often surprise specifiers approaching the choice for the first time.

5.1 THF: commodity

THF is a true commodity chemical, with millions of metric tons of global capacity, multiple integrated producers, and pricing that tracks closely with petroleum-derived 1,4-butanediol feedstock. Lead times are short and supply is generally reliable.

5.2 2-MeTHF: scaled specialty

2-MeTHF has scaled dramatically over the past decade as bio-based production routes have matured, particularly in China where furfural feedstock is plentiful. Per-kilogram cost is moderately higher than THF but well within the range that pharmaceutical and specialty users can absorb when workup efficiency or sustainability positioning justifies the premium. For market dynamics and pricing trends, see our market trends 2026 article.

5.3 3-MeTHF: specialty/research

3-MeTHF (CAS 13423-15-9) sits firmly in specialty-chemical territory. It is supplied by a small number of fine-chemical and research-chemical houses, typically in laboratory pack sizes (100 g to a few kilograms), at prices considerably higher per gram than 2-MeTHF or THF. Bulk industrial supply is essentially unavailable, which is why production-scale processes virtually always pivot to 2-MeTHF when an isomeric methyl-THF solvent is needed.

6. Decision Matrix: Which Solvent to Choose

The pattern that emerges from this matrix: 2-MeTHF is the right choice for most applications where THF was historically used, with the exceptions being commodity-cost-sensitive bulk processes (where THF still wins) and a narrow set of specialty research applications where 3-MeTHF's specific isomer matters. For practical Grignard chemistry, see our dedicated Grignard reactions article; for green chemistry positioning, see our green solvent & biomass article.

7. Frequently Asked Questions

Q1. Is the CAS number for 3-methyltetrahydrofuran 3188-00-9 or 13423-15-9?

The correct CAS for 3-methyltetrahydrofuran (3 methyl tetrahydrofuran) is 13423-15-9. The number 3188-00-9 sometimes appears in old catalogs or procurement systems, but it actually identifies a different compound entirely. Always confirm CAS numbers against the supplier's COA before placing an order, as a mismatch can result in delivery of the wrong material.

Q2. Can 3-MeTHF be used as a drop-in replacement for 2-MeTHF?

Chemically, the two isomers behave similarly in most reactions, but 3-MeTHF is essentially a research-scale specialty chemical. Bulk industrial supply is not realistic for production processes. If a specifier wants the methylated-tetrahydrofuran behavior, the practical choice for any scale beyond grams is 2-MeTHF.

Q3. Why is 2-MeTHF more peroxide-resistant than THF?

Peroxide formation begins with hydrogen abstraction at the carbon next to the ether oxygen. In 2-MeTHF, one of those positions carries a methyl group, which sterically and electronically hinders the abstraction step. THF has no such substitution, so both alpha positions are fully exposed to attack.

Q4. Are there reactions where THF outperforms 2-MeTHF?

Yes. Reactions that benefit from full water miscibility (some homogeneous catalysis, certain workup protocols), unit-cost-driven bulk chemistry, and a few polymer initiations sensitive to ring substitution can favor THF. The detailed cases are discussed in our Grignard & organometallic article, Section 6.

Q5. How do I source small quantities of 3-MeTHF for research?

Specialty research chemical suppliers and a small number of fine-chemical houses sell 3-MeTHF in laboratory pack sizes. Expect prices considerably higher per gram than 2-MeTHF and lead times of several weeks. For larger batches (kilogram scale or above), custom synthesis becomes the practical option, and few producers will quote it.