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Trimethylamine

C3H9N organic

Properties

StateGas at room temperature (bp 2.9°C); commonly sold as 40% aqueous solution
ColorColorless
SolubilityVery soluble in water (890 g/L at 20°C); soluble in ethanol and diethyl ether
Melting Point-117.1°C
Boiling Point2.9°C

About Trimethylamine

Trimethylamine is the molecule responsible for the smell of dead fish — and that's not a metaphor or an analogy, it's a chemical identification. Marine fish accumulate trimethylamine N-oxide (TMAO) at internal concentrations of 50-300 mM as an osmolyte that counters the protein-destabilizing effect of urea and high pressure (deep-sea fish have proportionally more TMAO than shallow species). Fresh fish has almost no detectable TMA, but within hours of death, bacterial trimethylamine-N-oxide reductase enzymes from species like Shewanella putrefaciens and Photobacterium phosphoreum reduce TMAO to TMA, and the spoilage clock starts ticking. The detection threshold for TMA in air sits around 0.4 ppb — humans can smell rotting fish from across a room because evolution wired our olfactory system specifically to flag this molecule as a food-safety warning. In humans, the metabolic disorder trimethylaminuria (fish odor syndrome) results from loss-of-function mutations in the FMO3 gene, which normally oxidizes dietary TMA back to odorless TMAO in the liver — affected individuals excrete TMA in sweat, breath, and urine, often diagnosed only in adolescence. Industrially, TMA is the highest-volume tertiary amine produced worldwide, made by the Leonard process (methanol + ammonia over Al2O3 at 350 °C), with global production around 200,000 tonnes per year. The largest single use is choline chloride synthesis (TMA + ethylene oxide + HCl) for animal feed supplementation, followed by quaternary ammonium surfactants like benzalkonium chloride and cetyltrimethylammonium bromide (CTAB), and ion-exchange resin manufacture.

Where you'll encounter it

If you've ever opened a refrigerator containing fish that's been there three days too long, taken a deep breath of low tide at a beach with rotting kelp, or squeezed a lemon onto baked cod to cut the smell, you've worked with the chemistry of trimethylamine. The lemon trick is acid-base chemistry in action: TMA (pKa of conjugate acid 9.8) is volatile as the free amine but locks into the non-volatile trimethylammonium cation when protonated by citric acid, so the smell drops immediately even though the molecule is still there. In a chemical plant making choline chloride for poultry feed, TMA arrives by tank truck as a 30-40% aqueous solution and reacts with ethylene oxide in HCl to give the choline product — the same molecule that becomes acetylcholine in animal nervous systems. In a biochemistry lab cloning the human FMO3 gene to study trimethylaminuria, the diagnostic test for affected patients is to dose them with 600 mg of free choline and measure the urinary TMAO/TMA ratio over 8 hours.

Common Uses

  • Feedstock for choline chloride synthesis (animal feed supplement) at hundreds of kt/year scale
  • Quaternary ammonium surfactant precursor: benzalkonium chloride disinfectants and CTAB cationic surfactant
  • Strong-base anion exchange resin synthesis (functionalization of chloromethylated polystyrene beads)
  • Mining flotation reagent and corrosion inhibitor formulations in oilfield service chemistry
  • Specialty organic synthesis base and source of the trimethylammonium leaving group in Hofmann elimination

Safety Information

GHS: H220 (extremely flammable gas), H302 (harmful if swallowed), H312 (harmful in contact with skin), H314 (severe burns and serious eye damage from concentrated solution), H332 (harmful if inhaled), H335 (respiratory irritation). OSHA PEL 10 ppm 8-hour TWA, ACGIH TLV 5 ppm TWA. The pure compressed gas forms explosive mixtures with air across roughly 2-12% v/v. Aqueous 40% solutions are corrosive to skin and eyes and release flammable vapors above 0 °C. Detection threshold (~0.4 ppb in air) is far below the irritant threshold, so an operator who can smell TMA strongly is already dangerously over the TLV. Ventilated cylinders, gas detectors, and full PPE required for any process-scale handling.

This safety summary is for educational reference only and may not be complete. It is not a substitute for Safety Data Sheets (SDS), medical advice, or professional chemical safety guidance. Always consult appropriate SDS and qualified professionals before handling chemicals.

Constituent Elements

Frequently Asked Questions

What is the molar mass of trimethylamine?
Trimethylamine ((CH3)3N) has a molar mass of 59.111 g/mol — three carbons at 12.011 give 36.033, nine hydrogens at 1.008 give 9.072, and one nitrogen contributes 14.007. The 40% aqueous reagent solutions sold by Sigma-Aldrich contain about 6.77 mol of TMA per liter, so a 100 mL bottle holds 0.677 mol — useful when dispensing equivalents into a quaternary ammonium synthesis.
Why does fish smell like trimethylamine?
Marine fish accumulate trimethylamine N-oxide (TMAO) at 50-300 mM internal concentration as an osmolyte that protects proteins against urea denaturation and high pressure (deep-sea species pack more TMAO than shallow ones). After death, spoilage bacteria like Shewanella putrefaciens express trimethylamine-N-oxide reductase that reduces TMAO to volatile, smelly TMA. Fresher fish has less TMA. Acidic marinades work because protonating TMA to its non-volatile trimethylammonium form locks the smell out of the headspace, even though the molecule is still chemically present in the flesh.
What is trimethylaminuria?
Trimethylaminuria — sometimes called fish odor syndrome — is a rare autosomal recessive metabolic disorder caused by loss-of-function mutations in the FMO3 gene. The flavin-containing monooxygenase 3 enzyme normally oxidizes dietary TMA (from choline, lecithin, and seafood) back to odorless TMAO in the liver. When FMO3 is impaired, unmetabolized TMA accumulates and is excreted in sweat, breath, and urine, producing a persistent fishy body odor that often goes undiagnosed until adolescence. Diagnosis uses a choline-loading test followed by urinary TMAO/TMA ratio measurement; management is dietary restriction of choline and supplementation with antibiotics that suppress gut microbial TMA production.