Urea, also called carbamide (because it is a diamide of carbonic acid), is an organic compound with chemical formula . This amide has two amino groups (−) joined by a carbonyl functional group (−C(=O)−). It is thus the simplest amide of carbamic acid.
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 showed 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°. In solid urea, the oxygen center is engaged in two hydrogen bonds. The resulting hydrogen-bond network is probably established at the cost of efficient molecular packing: The structure is quite open, the ribbons forming tunnels with square cross-section. The carbon in urea is described as sp hybridized, the bonds have significant double bond character, and the carbonyl oxygen is relatively basic. Urea's high aqueous solubility reflects its ability to engage in extensive hydrogen bonding with water.
By virtue of its tendency to form porous frameworks, urea has the ability to trap many organic compounds. In these so-called clathrates, the organic "guest" molecules are held in channels formed by interpenetrating helices composed of hydrogen-bonded urea molecules. In this way, urea-clathrates have been well investigated for separations.
Reactions
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:
At higher temperatures it converts to a range of condensation products, including cyanuric acid , guanidine , and melamine.
Hydrolysis In aqueous solution, urea slowly equilibrates with ammonium cyanate. This elimination reaction 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. For this reason, pure urea solutions should be freshly prepared and used, as aged solutions may develop a significant concentration of cyanate ( in urea). Dissolving urea in ultrapure water followed by removing ions (i.e. cyanate) with a mixed-bed ion-exchange resin and storing that solution at is a recommended preparation procedure. However, cyanate will build back up to significant levels within a few days. Alternatively, adding ammonium chloride to a concentrated urea solution decreases formation of cyanate because of the common ion effect.
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.
Related compounds
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
More than 90% of world industrial production of urea is for use as a nitrogen-release fertilizer. Urea has the highest nitrogen content of all solid nitrogenous fertilizers in common use. Therefore, it has a low transportation cost per unit of nitrogen nutrient. Urea breaks down in the soil to give ammonium ions (). The ammonium is taken up by the plant through its roots. In some soils, the ammonium is oxidized by bacteria to give nitrate (), which is also a nitrogen-rich plant nutrient. The loss of nitrogenous compounds to the atmosphere and runoff is wasteful and environmentally damaging so urea is sometimes modified to enhance the efficiency of its agricultural use. Techniques to make controlled-release fertilizers that slow the release of nitrogen include the encapsulation of urea in an inert sealant, and conversion of urea into derivatives such as urea-formaldehyde compounds, which degrade into ammonia at a pace matching plants' nutritional requirements. The most common impurity of synthetic urea is biuret, which impairs plant growth.
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 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 is much easier and safer to handle and store than the more irritant, caustic and hazardous ammonia, so it is the reactant of choice. Trucks and cars using these catalytic converters need to carry a supply of diesel exhaust fluid, also sold as AdBlue, a solution of urea in water.
Laboratory uses Urea in concentrations up to 10 M is a protein denaturant as it disrupts the noncovalent bonds in the proteins. This property can be exploited to increase the solubility of some proteins. A mixture of urea and choline chloride is used as a deep eutectic solvent (DES), a substance similar to ionic liquid. When used in a deep eutectic solvent, urea gradually denatures the proteins that are solubilized..
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.