Diethylamine
Properties
| State | Liquid (colorless with strong fishy/ammoniacal odor) |
| Color | Colorless |
| Solubility | Miscible with water; miscible with ethanol, ether, and most organic solvents |
| Melting Point | -50°C |
| Boiling Point | 55°C |
About Diethylamine
Diethylamine is a low-molecular-weight secondary amine that hits a useful sweet spot in basicity: pKaH of the conjugate acid is 10.93, so in water it is fully protonated below pH ~9 and free base above pH ~12. That makes it a reliable proton sink for HCl-generating reactions like acyl chloride couplings and sulfonylations, where it is strong enough to deprotonate and absorb HCl but small enough to wash out cleanly during workup. The N-H bond gives it a reactivity that triethylamine lacks: diethylamine attacks acyl chlorides to give N,N-diethylamides (DEET being the best-known example, made by reacting m-toluoyl chloride with Et2NH), it forms N-nitrosamines on contact with nitrous acid (a known carcinogen issue in industrial water and rubber chemistry), and it makes carbamates with isocyanates. In peptide synthesis, diethylamine is the standard reagent for Fmoc deprotection — 20% Et2NH in DMF cleaves the Fmoc carbamate within minutes via the dibenzofulvene mechanism. In HPLC, sub-percent diethylamine is a common mobile-phase modifier for basic compounds on silica or C18, where it caps residual silanols and gives sharper peaks for amines and alkaloids. The smell is unpleasantly fishy at low ppb and unmistakably ammoniacal at higher concentrations — it is one of those reagents you can detect in a stockroom from across the room.
Where you'll encounter it
If you have ever run an Fmoc-strategy peptide synthesis on a Wang or Rink-amide resin, you have washed the column with a 20% diethylamine in DMF solution to take off the Fmoc group between residues. The same bottle of diethylamine goes back into use as a base in coupling reactions where you are not worried about the N-H reactivity. In HPLC method development for tertiary amine drugs (lidocaine, propranolol, and the like), 0.1% diethylamine in the aqueous phase is a textbook tail-suppression trick.
Common Uses
- Standard reagent for Fmoc deprotection in solid-phase peptide synthesis (typically 20% in DMF)
- Acid scavenger in acyl chloride and sulfonyl chloride couplings on small-molecule scale
- Precursor for DEET (N,N-diethyl-meta-toluamide) synthesis by reaction with m-toluoyl chloride
- Mobile-phase silanol-capping additive at 0.05-0.1% for basic-drug HPLC on C18 columns
- Pharmaceutical and agrochemical intermediate for tertiary-amide and ammonium-salt building blocks
- Rubber vulcanization accelerator precursor in the manufacture of dithiocarbamates and thiurams
- Corrosion inhibitor in steam-system water treatment via volatile-amine pH adjustment
- Fingermark visualization and chromatographic visualization reagent in forensic and analytical labs
Safety Information
Highly flammable — flash point -28 °C, vapor density 2.5, autoignition 312 °C. ACGIH TLV is 5 ppm 8-hour TWA with a 15 ppm STEL; OSHA PEL is 25 ppm 8-hour TWA. Corrosive to skin and eyes. The bigger sneaky hazard is N-nitrosodiethylamine formation on contact with nitrites or nitrosating agents — NDEA is an IARC Group 2A carcinogen and was the contaminant behind the 2018 worldwide valsartan and ranitidine recalls. GHS: H225 (highly flammable), H302+H332 (harmful if swallowed/inhaled), H311 (toxic in skin contact), H314 (severe skin burns and eye damage). Handle in a well-ventilated fume hood with nitrile gloves and chemical splash goggles. Keep separate from acids, oxidizers, and any source of nitrite or nitrous acid.
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.