3-Methyl thiophene-2-carboxylic acid first turned up in research circles in the early decades of sulfur-containing heterocyclic chemistry. Back in the post-war years, chemists explored thiophene rings as building blocks for dyes, drugs, and agricultural chemicals. Growing interest in thiophene derivatives took off during the 1960s, thanks to new synthetic routes and the promise of diverse biological activity. Scientists recognized that modifying the thiophene scaffold—specifically, introducing a methyl and a carboxy group—could open doors to novel pharmaceuticals and crop protection agents. It often appeared in patent filings through the 1980s and beyond, as every tweak in structure meant the difference between an inactive compound and a blockbuster candidate. The story of this molecule sits within a wider tale: chemists always chasing that balance of function, feasibility, and fresh chemistry.
3-Methyl thiophene-2-carboxylic acid fits into an expanding library of heterocyclic acids used for downstream synthesis. With a methyl group attached to the third carbon of the thiophene ring and a carboxylic acid at the second, it carries unique reactivity thanks to the interplay between those positions. This arrangement lets it serve as a versatile intermediate—often used in constructing active pharmaceutical ingredients, agrochemicals, and organic electronic materials. It’s not the flashiest compound on a bench, but its structure opens up a toolbox of transformations. Research labs and industrial platforms alike often keep this carboxylic acid in stock for building complex molecules, exploiting its handle for both further derivatization and conjugation.
At room temperature, 3-methyl thiophene-2-carboxylic acid tends to appear as a white or off-white crystalline powder, although slight yellowing isn't rare due to minor oxidation. It doesn't dissolve well in water but dissolves readily in many polar organic solvents, including ethanol, acetone, and dimethyl sulfoxide. Its melting point typically falls between 90°C and 120°C, reflecting strong crystal lattice forces typical for carboxylic acids. The molecule weighs in at about 142 g/mol, with a noticeable sulfur odor—a hallmark of thiophene compounds that still catches people off guard in the lab. The aromatic thiophene ring shows significant stability, fairly resistant to reduction but eager for a range of substitution reactions. Acid dissociation constants (pKa) match what you’d expect from a benzoic acid derivative, making it suitable for use in pH-sensitive syntheses.
Specifications for 3-methyl thiophene-2-carboxylic acid target purity above 98%, often confirmed by high-performance liquid chromatography and NMR analysis. Small traces of related thiophene derivatives or minor organic acids appear as impurities in off-spec lots. Manufacturers label containers with standard chemical names, hazard pictograms, and QR codes to track batch history. Labels include UN numbers and recommendations for storage—typically sealed in dry, cool conditions out of sunlight. Experienced chemists and handlers appreciate clear labeling, since the smell alone doesn’t always reveal what’s inside a flask. Knowing the grade—analytical, technical, or high-purity—matters a lot depending on downstream use, especially when the next steps move toward regulated applications like pharmaceuticals.
Several routes lead to 3-methyl thiophene-2-carboxylic acid, but the most common starts with the thiophene ring itself. Chemists often employ Friedel–Crafts acylation, introducing a methyl group at the 3-position with methyl halides and Lewis acid catalysts. Carboxylation typically follows, sometimes utilizing metal-catalyzed carbonylation or transition metal-promoted direct functionalization. Another reliable path runs through Vilsmeier–Haack formylation, introducing a formyl group, followed by methylation and subsequent oxidation to the carboxylic acid. Each step requires strict control of temperature, solvents, and reaction times, as over-alkylation or ring degradation can lure the impatient. Scale-up in industry brings its own tweaks, such as flow chemistry adaptations and greener solvents, but the core logic remains: control the position, control the product.
The molecule’s carboxylic acid group offers easy access to esters, amides, and acid chlorides, making it a favorite for coupling reactions. Standard peptide synthesis methods attach this acid to amines or alcohols with carbodiimide or coupling agents. The methyl group, set at the 3-position, steers electrophilic aromatic substitution toward remaining open carbons, guiding functionalizations away from unwanted side products. Oxidation of the methyl can yield the corresponding aldehyde or alcohol, providing even more variety for organic synthesis. On the thiophene ring, halogenation, nitration, and sulfonation open the door to further utility in medicinal or polymer chemistry. These modification pathways supply both researchers and manufacturers with a range of derivatives, many of which display unique behavior in the body, in plants, or in electronic materials.
Catalogs and journals call 3-methyl thiophene-2-carboxylic acid by several names, with “2-carboxy-3-methylthiophene” often top of the list. Older literature sometimes refers to it as “β-carboxy-3-methylthiophene,” reflecting historical nomenclature conventions. Product listings show it under “3-Methyl-2-thiophenecarboxylic acid” or, more rarely, “3-MT-2-CA.” These variations stem from the standardization efforts of IUPAC through the 20th century. Recognizing synonyms prevents mix-ups when ordering or interpreting older research: more than one chemist has ordered the wrong acid because a vendor used local labeling standards. CAS numbers provide a consistent anchor—one code to rule out ambiguity in purchasing, inventory, or regulatory compliance.
Handling thiophene derivatives means you work with volatile organic compounds, some of which bring moderate inhalation risks and skin irritancy. 3-Methyl thiophene-2-carboxylic acid falls into the “caution, but not high alert” category. Users wear gloves, eye protection, and work in well-ventilated spaces or fume hoods. Safety data sheets stress the importance of avoiding prolonged skin contact or accidental ingestion, as metabolic pathways for thiophene compounds sometimes yield reactive metabolites. Storage in airtight containers slows degradation and reduces the chance for moisture-induced hydrolysis or mold growth. Disposal methods stick to licensed solvent waste handling, with local permits and documentation needed for large-scale streams. Major chemical suppliers conduct extensive hazard assessments, and many university labs adopt institutional protocols above the regulatory minimum.
This compound shows up most in organic synthesis and pharmaceutical R&D, acting as both a building block and a test substrate. Its tailored reactivity and spatial orientation on the thiophene ring help medicinal chemists fine-tune lead compounds for drug discovery. Agrochemical firms use it in screening programs, looking for new herbicides and fungicides. Materials scientists investigate its role as a monomer or additive for organic conductors, OLEDs, and sensory polymers, seeking high-performance properties for electronics. While it doesn’t headline many commercial products directly, it underpins research pipelines — giving both industry and academia the tools to go after tougher scientific and practical problems.
University and industry labs continue to draw on 3-methyl thiophene-2-carboxylic acid for exploratory research, linking it with new compounds that show promise as clinical candidates or advanced materials. Research articles track its reactivity across cross-coupling, late-stage functionalization, and bioisosteric replacement strategies. Funding often supports screening programs that convert this acid into larger libraries for biological assays. In the last decade, green chemistry innovations have shifted attention to cleaner synthesis methods—minimizing hazardous reagents, reducing energy use, and recycling solvents. Collaborative projects between chemical suppliers and research teams work toward more sustainable supply chains and broader regulatory approval, clearing roadblocks on the path from bench to large-scale application.
Animal and cell studies of thiophene and its derivatives make up much of the toxicity literature. 3-Methyl thiophene-2-carboxylic acid itself hasn’t shown the acute toxicity common to more reactive sulfur-containing aromatics; it generally features low to moderate oral and dermal toxicity in lab animals. Chronic exposure data remain limited. Some studies indicate mild mutagenicity at high concentrations, prompting an emphasis on PPE and exposure controls. Researchers continue to investigate its metabolic fate—especially in mammals—since oxidation may produce electrophilic intermediates that could stress liver enzymes and induce oxidative damage. Experience in the research lab has shown that, treated with respect and correct safety practices, this molecule presents manageable risks compared to many organic synthons with greater volatility or bioactivity.
As organic synthesis moves into the era of precise molecular construction, 3-methyl thiophene-2-carboxylic acid will remain a go-to starting point for new pharmaceuticals and specialty polymers. With the demand for sustainable and efficient synthetic methods rising, interest in streamlining its production grows. Researchers focus on catalysis, flow chemistry, and bio-based starting materials to reduce environmental impact. As medicinal chemistry projects demand new scaffolds for treating diseases that resist existing drugs, the unique combination of thiophene and carboxylic functionality allows rapid expansion of compound libraries. Advances in computational chemistry enable tight prediction of its reactivity, accelerating the design of new derivatives. In the landscape of future chemical manufacturing, this compound stands to play an outsized role, supporting a shift to molecules that hit precise therapeutic, agronomic, and materials targets—and shaping the next chapters of chemical innovation.
