| Solvent1=acetonitrile

| Solubility1=

| Solvent2 = ethanol

| Solubility2 =

| Solvent3 = glycerol

| Solubility3 =

| MeltingPtC = 132.4

| MeltingPt_ref =

| VaporPressure =

| pKa = 0.1

Urea serves an important role in the cellular metabolism of nitrogen-containing compounds by animals and is the main nitrogen-containing substance in the urine of mammals. The word urea is Neo-Latin, , .

It is a colorless, odorless solid, highly soluble in water, and practically non-toxic. Dissolved in water, it is neither acidic nor alkaline. The body uses it in many processes, most notably nitrogen excretion. In the liver, it forms by the condensation of ammonia () and carbon dioxide () in the urea cycle. Urea is widely used in fertilizers as a source of nitrogen (N).

In 1828, Friedrich Wöhler discovered that urea can be produced from inorganic starting materials, an important conceptual milestone in chemistry. This showed for the first time that a substance previously known only as a byproduct of life could be synthesized in the laboratory from non-biological starting materials, thereby contradicting the widely held doctrine of vitalism, which stated that organic compounds could only be derived from living organisms.

Molecular and crystal structure

The structure of the molecule of urea is . The urea molecule is planar when in a solid crystal because of sp hybridization of the N orbitals. It is non-planar with C symmetry when in the gas phase or in aqueous solution, with and bond angles that are intermediate between the trigonal planar angle of 120° and the tetrahedral angle of 109.5°.

Reactions

thumb|right|Structure of showing intramolecular hydrogen bonds. Color code: blue = N, red = O.

Basicity

Urea is a weak base, with a pK of 13.9. When combined with strong acids, it undergoes protonation at oxygen to form uronium salts. It is a Lewis base, forming metal complexes of the type .

N-functionalization

As an electron-rich amide, urea readily undergoes N-functionalization by electrophilic reagents. This property gives rise to several reagents. Nitration occurs at the amine to give N-nitrourea. Chlorination similarly gives N-chlorourea.

Transamination

Urea undergoes transamination. For example, treatment with anilinium gives both N-phenylurea and N,N'-diphenylurea. N-Methylurea can be prepared by a similar acid-catalyzed pathway.

Heterocyclization

Urea, being a multifunctional, is a versatile precursor to heterocycles. It reacts with malonic esters to make barbituric acids. With hydroxyketones, urea condenses to give glyoxalones. It is a precursor to pyrimidines.

Thermolysis

Molten urea decomposes into ammonium cyanate at about , and into ammonia and isocyanic acid above :

:

Heating above yields biuret and triuret via reaction with isocyanic acid: cogenerates isocyanic acid, which can carbamylate proteins, in particular the N-terminal amino group, the side chain amino of lysine, and to a lesser extent the side chains of arginine and cysteine. Each carbamylation event adds to the mass of the protein, which can be observed in protein mass spectrometry. However, cyanate will build back up to significant levels within a few days.

Analysis

Urea is readily quantified by a number of different methods, such as the diacetyl monoxime colorimetric method, and the Berthelot reaction (after initial conversion of urea to ammonia via urease). These methods are amenable to high throughput instrumentation, such as automated flow injection analyzers and 96-well micro-plate spectrophotometers.

Urea is the parent for a class of chemical compounds that share the same functional group. Namely, such compounds have a carbonyl group attached to two organic amine residues: , where groups are hydrogen (–H), organyl or other groups. Examples include carbamide peroxide, allantoin, and hydantoin. Ureas are closely related to biurets and related in structure to amides, carbamates, carbodiimides, and thiocarbamides.

Uses

Agriculture

left|thumb|A plant in [[Bangladesh that produces urea fertilizer]]

More than 90% of world industrial production of urea is for use as a nitrogen-release fertilizer.

Resins

Urea is a raw material for the manufacture of formaldehyde based resins, such as UF, MUF, and MUPF, used mainly in wood-based panels, for instance, particleboard, fiberboard, OSB, and plywood.

Explosives

Urea can be used in a reaction with nitric acid to make urea nitrate, a high explosive that is used industrially and as part of some improvised explosive devices.

Automobile systems

Urea is used in Selective Non-Catalytic Reduction (SNCR) and Selective Catalytic Reduction (SCR) reactions to reduce the nitrogen oxide| pollutants in exhaust gases from diesel, dual fuel, and lean-burn natural gas engines. The BlueTec system, for example, injects a water-based urea solution into the exhaust system. Ammonia () produced by the hydrolysis of urea reacts with nitrogen oxides () and is converted into nitrogen gas () and water within the catalytic converter. The conversion of noxious to innocuous is described by the following simplified global equation:

:

When urea is used, a pre-reaction (hydrolysis) occurs to first convert it to ammonia:

:

Being a solid highly soluble in water ( at ),

Urea in concentrations up to 8 M can be used to make fixed brain tissue transparent to visible light while still preserving fluorescent signals from labeled cells. This allows for much deeper imaging of neuronal processes than previously obtainable using conventional one photon or two photon confocal microscopes.

Medical use

Urea-containing creams are used as topical dermatological products to promote rehydration of the skin. Urea 40% is indicated for psoriasis, xerosis, onychomycosis, ichthyosis, eczema, keratosis, keratoderma, corns, and calluses. If covered by an occlusive dressing, 40% urea preparations may also be used for nonsurgical debridement of nails. Urea 40% "dissolves the intercellular matrix" of the nail plate. Only diseased or dystrophic nails are removed, as there is no effect on healthy portions of the nail.

Urea has been studied as a diuretic. It was first used by Dr. W. Friedrich in 1892. In a 2010 study of ICU patients, urea was used to treat euvolemic hyponatremia and was found safe, inexpensive, and simple.

Like saline, urea has been injected into the uterus to induce abortion, although this method is no longer in widespread use.

The blood urea nitrogen (BUN) test is a measure of the amount of nitrogen in the blood that comes from urea. It is used as a marker of renal function, though it is inferior to other markers such as creatinine because blood urea levels are influenced by other factors such as diet, dehydration, and liver function.

Urea has also been studied as an excipient in drug-coated balloon (DCB) coating formulations to enhance local drug delivery to stenotic blood vessels. Urea, when used as an excipient in small doses () to coat DCB surface was found to form crystals that increase drug transfer without adverse toxic effects on vascular endothelial cells.

Urea labeled with carbon-14 or carbon-13 is used in the urea breath test, which is used to detect the presence of the bacterium Helicobacter pylori (H. pylori) in the stomach and duodenum of humans, associated with peptic ulcers. The test detects the characteristic enzyme urease, produced by H. pylori, by a reaction that produces ammonia from urea. This increases the pH (reduces the acidity) of the stomach environment around the bacteria. Similar bacteria species to H. pylori can be identified by the same test in animals such as apes, dogs, and cats (including big cats).

Miscellaneous

  • An ingredient in diesel exhaust fluid (DEF), which is 32.5% urea and 67.5% de-ionized water. DEF is sprayed into the exhaust stream of diesel vehicles to break down dangerous emissions into harmless nitrogen and water.
  • A component of animal feed, providing a relatively cheap source of non-protein nitrogen to promote growth.
  • A non-corroding alternative to rock salt for road de-icing. It is often the main ingredient of pet friendly salt substitutes although it is less effective than traditional rock salt or calcium chloride.
  • A main ingredient in hair removers such as Nair and Veet.
  • A browning agent in factory-produced pretzels.
  • An ingredient in some skin cream, moisturizers, hair conditioners, and shampoos.
  • A cloud seeding agent, along with other salts.
  • A flame-proofing agent, commonly used in dry chemical fire extinguisher charges such as the urea-potassium bicarbonate mixture.
  • Along with diammonium phosphate, as a yeast nutrient, for fermentation of sugars into ethanol.
  • A nutrient used by plankton in ocean nourishment experiments for climate engineering purposes.
  • As an additive to extend the working temperature and open time of hide glue.
  • As a solubility-enhancing and moisture-retaining additive to dye baths for textile dyeing or printing.
  • As an optical parametric oscillator in nonlinear optics.
  • To help prepare an alpine skiing course by hardening the snow into a icier surface to maintain the integrity of the course.

Physiology

Amino acids, e.g. from ingested food, can be oxidized by the body as an alternative source of energy, yielding urea and carbon dioxide. The oxidation pathway starts with the removal of the amino group by a transaminase; the amino group is then fed into the urea cycle. The first step in the conversion of amino acids into metabolic waste in the liver is removal of the alpha-amino nitrogen, which produces ammonia. Because ammonia is toxic, it is excreted immediately by fish, converted into uric acid by birds, and converted into urea by mammals.

Ammonia () is a common byproduct of the metabolism of nitrogenous compounds. Ammonia is smaller, more volatile, and more mobile than urea. If allowed to accumulate, ammonia would raise the pH in cells to toxic levels. Therefore, many organisms convert ammonia to urea, even though this synthesis has a net energy cost. Being practically neutral and highly soluble in water, urea is a safe vehicle for the body to transport and excrete excess nitrogen.

Urea is synthesized in the body of many organisms as part of the urea cycle, either from the oxidation of amino acids or from ammonia. In this cycle, amino groups donated by ammonia and -aspartate are converted to urea, while -ornithine, citrulline, -argininosuccinate, and -arginine act as intermediates. Urea production occurs in the liver and is regulated by N-acetylglutamate. Urea is then dissolved into the blood (in the reference range of 2.5 to 6.7 mmol/L) and further transported and excreted by the kidney as a component of urine. In addition, a small amount of urea is excreted (along with sodium chloride and water) in sweat.

In water, the amine groups undergo slow displacement by water molecules, producing ammonia, ammonium ions, and bicarbonate ions. For this reason, old, stale urine has a stronger odor than fresh urine.

Humans

The cycling of and excretion of urea by the kidneys is a vital part of mammalian metabolism. Besides its role as carrier of waste nitrogen, urea also plays a role in the countercurrent exchange system of the nephrons, that allows for reabsorption of water and critical ions from the excreted urine. Urea is reabsorbed in the inner medullary collecting ducts of the nephrons, thus raising the osmolarity in the medullary interstitium surrounding the thin descending limb of the loop of Henle, which makes the water reabsorb.

By action of the urea transporter 2, some of this reabsorbed urea eventually flows back into the thin descending limb of the tubule, through the collecting ducts, and into the excreted urine. The body uses this mechanism, which is controlled by the antidiuretic hormone, to create hyperosmotic urine — i.e., urine with a higher concentration of dissolved substances than the blood plasma. This mechanism is important to prevent the loss of water, maintain blood pressure, and maintain a suitable concentration of sodium ions in the blood plasma.

The equivalent nitrogen content (in grams) of urea (in mmol) can be estimated by the conversion factor . Furthermore, of nitrogen is roughly equivalent to of protein, and of protein is roughly equivalent to of muscle tissue. In situations such as muscle wasting, of excessive urea in the urine (as measured by urine volume in litres multiplied by urea concentration in mmol/L) roughly corresponds to a muscle loss of .

Other species

In aquatic organisms the most common form of nitrogen waste is ammonia, whereas land-dwelling organisms convert the toxic ammonia to either urea or uric acid. Urea is found in the urine of mammals and amphibians, as well as some fish. Birds and saurian reptiles have a different form of nitrogen metabolism that requires less water, and leads to nitrogen excretion in the form of uric acid. Tadpoles excrete ammonia, but shift to urea production during metamorphosis. Despite the generalization above, the urea pathway has been documented not only in mammals and amphibians, but in many other organisms as well, including birds, invertebrates, insects, plants, yeast, fungi, and even microorganisms.

Adverse effects

Urea can be irritating to skin, eyes, and the respiratory tract. Repeated or prolonged contact with urea in fertilizer form on the skin may cause dermatitis.

High concentrations in the blood can be damaging. Ingestion of low concentrations of urea, such as are found in typical human urine, are not dangerous with additional water ingestion within a reasonable time-frame. Many animals (e.g. camels, rodents or dogs) have a much more concentrated urine which may contain a higher urea amount than normal human urine.

Urea can cause algal blooms to produce toxins, and its presence in the runoff from fertilized land may play a role in the increase of toxic blooms.

The substance decomposes on heating above melting point, producing toxic gases, and reacts violently with strong oxidants, nitrites, inorganic chlorides, chlorites and perchlorates, causing fire and explosion.

History

Urea was first obtained by Herman Boerhaave in 1727 from evaporates of urine. The discovery is also attributed to the French chemist Hilaire Rouelle as well as William Cruickshank. In 1773, Hilaire Rouelle obtained crystals containing urea by evaporating human urine and treating the concentrate with alcohol. This method was aided by Carl Wilhelm Scheele's discovery that crystals precipitated when urine was treated by concentrated nitric acid.

Uremic frost was first described in 1856 by the Austrian physician Anton Drasche. Uremic frost has become rare since the advent of dialysis. It is the classical pre-dialysis era description of crystallized urea deposits over the skin of patients with prolonged kidney failure and severe uremia.

Historical preparation

Antoine François, comte de Fourcroy and Louis Nicolas Vauquelin discovered in 1799 that the nitrated crystals were identical to Rouelle's substance and invented the term "urea."

Berzelius further improved the purification of urea. In 1817 William Prout determining the chemical composition. In the evolved procedure, urea was precipitated as urea nitrate by adding strong nitric acid to urine. To purify the resulting crystals, they were dissolved in boiling water with charcoal and filtered. After cooling, pure crystals of urea nitrate form. To reconstitute the urea from the nitrate, the crystals are dissolved in warm water, and barium carbonate added. The water is then evaporated and anhydrous alcohol added to extract the urea. This solution is drained off and evaporated, leaving pure urea.

Wöhler's experiments

In 1828, the German chemist Friedrich Wöhler prepared urea by treating silver cyanate with ammonium chloride.

:

This was one of the first artificial syntheses of biological compounds from inorganic starting materials, without the involvement of living organisms. The results of this experiment implicitly discredited vitalism, the theory that the chemicals of living organisms are fundamentally different from those of inanimate matter. This insight was important for the development of organic chemistry. His discovery prompted Wöhler to write triumphantly to Jöns Jakob Berzelius:

His second sentence was incorrect. Ammonium cyanate and urea are two different chemicals with the same empirical formula , which are in chemical equilibrium heavily favoring urea under standard conditions.

Laboratory preparation

Urea can be produced by heating ammonium cyanate to .

:

Industrial production

In 2020, worldwide production capacity was approximately 180 million tonnes.

For use in industry, urea is produced from synthetic ammonia and carbon dioxide. As large quantities of carbon dioxide are produced during the ammonia manufacturing process as a byproduct of burning hydrocarbons to generate heat (predominantly natural gas, and less often petroleum derivatives or coal), urea production plants are almost always located adjacent to the site where the ammonia is manufactured.

Synthesis

thumb|right | Urea plant using ammonium carbamate briquettes, Fixed Nitrogen Research Laboratory, ca. 1930

The basic process, patented in 1922, is called the Bosch–Meiser urea process after its discoverers Carl Bosch and Wilhelm Meiser. The process consists of two main equilibrium reactions, with incomplete conversion of the reactants. The first is carbamate formation: the fast exothermic reaction of liquid ammonia with gaseous carbon dioxide () at high temperature and pressure to form ammonium carbamate ():

:( at and )

The second is urea conversion: the slower endothermic decomposition of ammonium carbamate into urea and water:

In the conventional recycle processes, carbamate decomposition is promoted by reducing the overall pressure, which reduces the partial pressure of both ammonia and carbon dioxide, allowing these gasses to be separated from the urea product solution. The stripping process achieves a similar effect without lowering the overall pressure, by suppressing the partial pressure of just one of the reactants in order to promote carbamate decomposition. Instead of feeding carbon dioxide gas directly to the urea synthesis reactor with the ammonia, as in the conventional process, the stripping process first routes the carbon dioxide through the stripper. The stripper is a carbamate decomposer that provides a large amount of gas-liquid contact. This flushes out free ammonia, reducing its partial pressure over the liquid surface and carrying it directly to a carbamate condenser (also under full system pressure). From there, reconstituted ammonium carbamate liquor is passed to the urea production reactor. That eliminates the medium-pressure stage of the conventional recycle process. but it is sometimes desirable as a nitrogen source when used in animal feed.

Isocyanic acid HNCO and ammonia results from the thermal decomposition of ammonium cyanate , which is in chemical equilibrium with urea:

:

This decomposition is at its worst when the urea solution is heated at low pressure, which happens when the solution is concentrated for prilling or granulation (see below). The reaction products mostly volatilize into the overhead vapours, and recombine when these condense to form urea again, which contaminates the process condensate.

See also

  • Wöhler urea synthesis
  • Thiourea

Footnotes

References