Index
It is a tertiary amine where nitrogen is attached to three ethyl groups.
Triethylamine (TEA) is a very commonly used organic base. Diisopropylethylamine (DIEA) is a closely related organic base.
DIEA is more sterically hindered than TEA, therefore it is less prone to quaternization when used with highly reactive alkylating agents.
TEA has a boiling point of 89 C, making it easier to remove through rotovap distillation. DIEA has a boiling point of 127 C, making it most useful for reactions that exceed 90 C.
In most situations, TEA and DIEA can be used interchangeably. However, for certain situations, one is a better option than the other.
Nature
Triethylamine is a clear colorless to pale yellow liquid with a pungent astringency and a very bitter taste.
It is slightly smoky in air, slightly soluble in water, soluble in ethanol and ether. The aqueous solution is alkaline. It is flammable, its vapor can form an explosive mixture with air.
Preparation
It can be obtained by reacting ethanol and ammonia in the presence of hydrogen in a reactor equipped with a copper-nickel white earth catalyst under heating conditions (190 ± 2ºC and 165 ± 2ºC). The reaction also produces monoethylamine and diethylamine.
The product is condensed and then absorbed in ethanol to obtain crude triethylamine. Finally, it is separated, dehydrated and fractionated to obtain pure triethylamine.
Applications
Mainly used as a base in organic synthesis, catalysts, solvents and starting materials, they are also used as high energy fuel, rubber vulcanization accelerator, tetrafluoroethylene of polymerization inhibitors, surfactants, wetting agents, preservatives and fungicides.
Triethylamine is the simplest trisubstituted tertiary amine that is liquid at room temperature and is therefore widely used as a solvent and base in organic synthesis, generally abbreviated as Et3N, NEt3, or TEA.
It is one of the most commonly used organic bases in organic synthesis, with a boiling point of around 89 degrees Celsius, which is relatively easy to remove by distillation.
Hydrochloride and hydrobromide salts are not very soluble in an organic solvent such as diethyl ether and therefore can be isolated directly by filtration.
The simplest trimethylamine is a colorless gas under normal conditions and should be stored in a gas tank or stored as a 40% aqueous solution, which is not as easy to use as triethylamine.
Pharmacology and biochemistry
Absorption, distribution and excretion
The pharmacokinetics of the industrially important compound triethylamine (TEA) and its metabolite triethylamine-N-oxide (TEAO) were studied in four volunteers after oral and intravenous administration.
TEA was efficiently absorbed from the gastrointestinal (GI) tract, rapidly distributed, and partly metabolized to TEAO. There was no significant first-pass metabolism.
TEAO was also well absorbed from the gastrointestinal tract. Within the GI tract, TEAO was reduced to TEA (19%) and dealkylated to diethylamine (DEA; 10%). The apparent volumes of distribution during the elimination phase were 192 liters for TEA and 103 liters for TEAO.
Gastric intubation showed that there was a close association between TEA levels in plasma and gastric juice, the latter levels being 30 times higher. TEA and TEAO in plasma had half-lives of approximately 3 and 4 hours, respectively.
TEA exhalation was minimal. More than 90% of the dose was recovered in the urine as TEA and TEAO. TEA and TEAO urinary clearances indicated that, in addition to glomerular filtration, tubular secretion occurs.
For TEAO at high levels, the secretion appears saturable. Current data, in combination with previous studies, indicate that the sum of TEA and TEAO in urine can be used for biological monitoring of TEA exposure.
The objectives of the study were to evaluate the exposure to triethylamine (TEA) in the manufacture of cold box cores and to study the applicability of the measurement of urinary TEA in the evaluation of exposure.
Air samples were collected by pumping air through glass tubes filled with activated carbon, and urine samples were collected before and after the switch. TEA concentrations were determined by gas chromatography. TEA was measured in air and urine samples from the same shift.
Breathing zone measurements of 19 workers in 3 foundries were included in the study, and steady and continuous air measurements were also made in the same foundries. Pre- and post-exchange urine samples were analyzed for their TEA and triethylamine-N-oxide (TEAO) concentrations.
The TEA concentration range was 0.3-23 mg / m3 in the core manufacturers breathing zone. The 8-hour time-weighted average exposure levels were 1.3, 4.0, and 13 mg / m3 for the three smelters.
Most of the preset urinary TEA concentrations were below the detection limit, while the post-market urine TEA concentrations ranged from 5.6 to 171 mmol / mol creatinine.
TEAO concentrations were 4-34% (mean 19%) of the summed TEA + TEAO concentrations. The correlation between air and urine measurements was high (r = 0.96, p <0.001).
An airborne TEA concentration of 4.1 mg / m3 (the current time-weighted average cut-off value of 8 hr ACGIH) corresponded to a urinary concentration of 36 mmol / mol creatinine.
In 20 workers studied before, during and after exposure to triethylamine (TEA) in a polyurethane foam-producing plant, the amount of TEA and its metabolite triethylamine-N-oxide (TEAO) excreted in the urine corresponded to an average of 80% of the inhaled amount.
An average of 27% was TEAO, but with a pronounced inter-individual variation. Older subjects excreted more than younger ones; less than 0.3% was excreted as diethylamine.
Metabolism / Metabolites
Few studies have been conducted on the metabolism of industrially important aliphatic amines, such as triethylamine.
In general, amines that are not normally present in the body are assumed to be metabolized by monoamine oxidase and diamine oxidase (histaminase). Monoamine oxidase catalyzes the deamination of primary, secondary, and tertiary amines.
Ultimately, ammonia is formed and will turn into urea. The hydrogen peroxide formed is activated by catalase and it is believed that the aldehyde formed is converted to the corresponding carboxylic acid by the action of the aldehyde oxidase.
Five healthy volunteers were exposed by inhalation to triethylamine (TEA, four or eight hours at approximately 10, 20, 35 and 50 mg / m3), a compound widely used as a curing agent in polyurethane systems.
The analysis of plasma and urine showed that an average of 24% of the TEA is biotransformed into triethylamine-N-oxide (TEAO) but with a wide inter-individual variation (15-36%). The TEA and TEAO were eliminated quantitatively in the urine.
Plasma and urinary concentrations of TEA and TEAO decreased rapidly after the end of exposure (half the mean TEA time was 3.2 h).
In 20 workers studied before, during and after exposure to triethylamine (TEA) in a polyurethane foam-producing plant, the amount of TEA and its metabolite triethylamine-N-oxide (TEAO) excreted in the urine corresponded to an average of 80% of the inhaled amount.
An average of 27% was TEAO, but with a pronounced inter-individual variation. Older subjects excreted more than younger ones; less than 0.3% was excreted as diethylamine.
Biological half-life
Following an oral dose of triethylamine to four men, plasma triethylamine had a half-life of approximately 3 hours (range, 2.4-3.5 hours).
Safety and danger
Health hazard
Vapors irritate the nose, throat, and lungs, causing coughing, choking, and shortness of breath. Contact with the eyes causes severe burns. Chemical-soaked clothing causes skin burns.
Fire danger
May be ignited by heat, sparks, or flames. Vapors may form explosive mixtures with air. Vapors can travel to source of ignition and flash back.
Most vapors are heavier than air. They will spread along the ground and accumulate in low or confined areas (sewers, basements, tanks).
Vapor explosion hazard indoors, outdoors, or in sewers. Those substances designated with a (P) can polymerize explosively when heated or involved in a fire.
Runoff to the sewer can create a fire or explosion hazard. Containers may explode when heated. Many liquids are lighter than water.
Risk Summary
Acute (short-term) exposure of humans to triethylamine vapor causes eye irritation, corneal swelling, and halo vision.
People have complained of seeing “blue haze” or having “smoky vision.” These effects have been reversible when the exposure ceased.
Acute exposure can irritate the skin and mucous membranes in humans. Chronic (long-term) exposure of workers to triethylamine vapor has been shown to cause reversible corneal edema.
Chronic inhalation exposure has produced respiratory and haematological effects and eye damage in rats and rabbits.
No information is available on the reproductive, developmental, or carcinogenic effects of triethylamine in humans. Triethylamine has not been classified by EPA for potential carcinogenicity.
Toxicity
Carcinogen
Not classifiable as a human carcinogen.
Health effects
- Irritation: eyes, nose, throat.
- Marked skin.
- Pulmonary edema.
- Corneal damage.
Exposure routes
The substance can be absorbed into the body by inhalation, through the skin, and by ingestion.
Symptoms
In humans:
- Irritation of eyes, skin, respiratory system.
- Mild headache
- Dizziness
- Soft spot.
- Sickness.
- Tos.
- Throat pain.
- Difficulty breathing.
- Pulmonary edema (may be delayed).
- Redness
- Pain.
- Burns to the skin and eyes.
In animals:
- Damage to the myocardium, kidney, liver.
- Abdominal pain.
- Burning sensation
- Collapse the shock.
Eye symptoms
- Pain.
- Redness
- Blurry vision.
- Loss of vision
- Severe deep burns.
Ingestion symptoms
- Abdominal pain.
- Sensation of burning.
- Shock collapse.
Target organs
- Eyes.
- Skin.
- Respiratory system.
- Cardiovascular system.
- Liver.
- Kidneys.
Acute effects
Acute human exposure to triethylamine vapor causes eye irritation, corneal swelling, and halo vision. People have complained of seeing “blue haze” or having “smoky vision.” These effects have been reversible when the exposure ceased.
Acute exposure can irritate the skin and mucous membranes in humans.
Acute animal tests in rats, mice, and rabbits have shown that triethylamine has moderate acute inhalation toxicity, moderate to high acute toxicity from oral exposure, and high acute toxicity from dermal exposure.
Chronic effects
Chronic exposure of workers to triethylamine vapor has been shown to cause reversible corneal edema.
Chronic inhalation exposure has resulted in inflammation of the nasal passage in rats.
Thickening of the interalveolar walls of the lungs, accumulation of mucosa in the alveolar spaces of the lungs, and haematological effects have also been reported in rats chronically exposed by inhalation.
Chronic inhalation exposure to rabbits has been reported to cause lung irritation, edema, moderate peribronchitis, vascular thickening, eye damage, and, at higher levels, liver, kidney, and heart effects.
The Reference Concentration (RfC) for triethylamine is 0.007 milligrams per cubic meter (mg / m 3 ) based on inflammation of the nasal passages in rats.
The RfC is an estimate (with uncertainty perhaps spanning an order of magnitude) of continuous inhalation exposure to the human population (including sensitive subgroups) that is unlikely to have an appreciable lifetime risk of harmful non-carcinogenic effects.
It is not a direct estimator of risk but rather a benchmark for measuring potential effects.
At exposures increasingly higher than RfC, the possibility of adverse health effects increases. Lifetime exposure above the RfC does not necessarily imply an adverse health effect.
EPA has medium confidence in the studies on which the RfC was based because a concentration-response was evident, although a lower observed adverse effect level (LOAEL) could not be identified and a second species was not used.
Low confidence in the database, as there is only a single reproductive / developmental study, which is oral and therefore not useful for inhalation risk assessment, and there are no chronic studies; and, consequently, low confidence in the RfC.
The EPA has not established a Reference Dose (RfD) for triethylamine
Reproductive and developmental effects
No information is available on the reproductive or developmental effects of triethylamine in humans.
No reproductive or developmental effects were reported in a 3-generation study in rats exposed to triethylamine in drinking water; however, this study had limitations.
