Urea cycle enzymes
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Urea, also known as carbamide, 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 metabolism of nitrogen-containing compounds by animals and is the main nitrogen-containing substance in the urine of
mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
s. It is a colorless, odorless solid, highly soluble in water, and practically non-toxic ( is 15 g/kg for rats). Dissolved in water, it is neither
acid In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...
ic nor
alkaline In chemistry, an alkali (; from ar, القلوي, al-qaly, lit=ashes of the saltwort) is a base (chemistry), basic, ionic compound, ionic salt (chemistry), salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as ...
. The body uses it in many processes, most notably nitrogen excretion. The liver forms it by combining two ammonia molecules () with a carbon dioxide () molecule in the urea cycle. Urea is widely used in fertilizers as a source of nitrogen (N) and is an important
raw material A raw material, also known as a feedstock, unprocessed material, or primary commodity, is a basic material that is used to produce goods, finished goods, energy, or intermediate materials that are feedstock for future finished products. As feedst ...
for the
chemical industry The chemical industry comprises the companies that produce industrial chemicals. Central to the modern world economy, it converts raw materials (oil, natural gas, air, water, metals, and minerals) into more than 70,000 different products. The ...
. In 1828
Friedrich Wöhler Friedrich Wöhler () FRS(For) HonFRSE (31 July 180023 September 1882) was a German chemist known for his work in inorganic chemistry, being the first to isolate the chemical elements beryllium and yttrium in pure metallic form. He was the firs ...
discovered that urea can be produced from inorganic starting materials, which was 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 without biological starting materials, thereby contradicting the widely held doctrine of
vitalism Vitalism is a belief that starts from the premise that "living organisms are fundamentally different from non-living entities because they contain some non-physical element or are governed by different principles than are inanimate things." Wher ...
, which stated that only living organisms could produce the chemicals of life.


Uses


Agriculture

More than 90% of world industrial production of urea is destined 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 A nutrient is a substance used by an organism to survive, grow, and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi, and protists. Nutrients can be incorporated into cells for metabolic purposes or excret ...
. The most common impurity of synthetic urea is
biuret Biuret is a chemical compound with the chemical formula . It is a white solid that is soluble in hot water. A variety of organic derivatives are known. The term "biuret" also describes a family of organic compounds with the chemical formula , where ...
, which impairs plant growth. Urea breaks down in the soil to give ammonium. The ammonium is taken up by the plant. In some soils, the ammonium is oxidized by bacteria to give nitrate, which is also a plant nutrient. The loss of nitrogenous compounds to the atmosphere and runoff is both wasteful and environmentally damaging. For this reason, urea is sometimes pretreated or modified to enhance the efficiency of its agricultural use. One such technology is controlled-release fertilizers, which contain urea encapsulated in an inert sealant. Another technology is the conversion of urea into derivatives, such as formaldehyde, which degrades into ammonia at a pace matching plants' nutritional requirements.


Resins

Urea is a raw material for the manufacture of two main classes of materials:
urea-formaldehyde resin Urea-formaldehyde (UF), also known as urea-methanal, so named for its common synthesis pathway and overall structure, is a nontransparent thermosetting resin or polymer. It is produced from urea and formaldehyde. These resins are used in adhesive ...
s and urea-melamine-formaldehyde used in marine
plywood Plywood is a material manufactured from thin layers or "plies" of wood veneer that are glued together with adjacent layers having their wood grain rotated up to 90 degrees to one another. It is an engineered wood from the family of manufactured ...
.


Explosives

Urea can be used to make
urea nitrate Urea nitrate is a fertilizer-based high explosive that has been used in improvised explosive devices in Afghanistan, Pakistan, Iraq, and various terrorist acts elsewhere in the world such as in the 1993 World Trade Center bombings. It has a des ...
, 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 combustion from
diesel Diesel may refer to: * Diesel engine, an internal combustion engine where ignition is caused by compression * Diesel fuel, a liquid fuel used in diesel engines * Diesel locomotive, a railway locomotive in which the prime mover is a diesel engin ...
, dual fuel, and lean-burn natural gas engines. The BlueTec system, for example, injects a water-based urea solution into the exhaust system. Ammonia () first 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 (545 g/L at 25 °C), urea is much easier and safer to handle and store than the more irritant,
caustic Caustic most commonly refers to: * Causticity, a property of various corrosive substances ** Sodium hydroxide, sometimes called ''caustic soda'' ** Potassium hydroxide, sometimes called ''caustic potash'' ** Calcium oxide, sometimes called ''caus ...
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 Diesel exhaust fluid (DEF; also known as AUS 32 and marketed as AdBlue) is a liquid used to reduce the amount of air pollution created by a diesel engine. Specifically, DEF is an aqueous urea solution made with 32.5% urea and 67.5% deionized w ...
, a solution of urea in water.


Laboratory uses

Urea in concentrations up to 10 M is a powerful 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 Choline chloride is an organic compound with the formula CH3)3NCH2CH2OHl. It is bifunctional, containing both quaternary ammonium salt and an alcohol. The cation is choline, which occurs naturally. It is a white, water-soluble salt (chemistry ...
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 can in principle serve as a hydrogen source for subsequent power generation in
fuel cell A fuel cell is an electrochemical cell that converts the chemical energy of a fuel (often hydrogen) and an oxidizing agent (often oxygen) into electricity through a pair of redox reactions. Fuel cells are different from most batteries in requ ...
s. Urea present in urine/wastewater can be used directly (though bacteria normally quickly degrade urea). Producing hydrogen by electrolysis of urea solution occurs at a lower voltage () and thus consumes less energy than the electrolysis of water (). 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 An occlusive dressing is an air- and water-tight trauma medical dressing used in first aid. These dressings are generally made with a waxy coating so as to provide a total seal, and as a result do not have the absorbent properties of gauze pads. Th ...
, 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. This drug (as
carbamide peroxide Hydrogen peroxide - urea (also called Hyperol, artizone, urea hydrogen peroxide, and UHP) is a solid composed of equal amounts of hydrogen peroxide and urea. This compound is a white crystalline solid which dissolves in water to give free hydrogen ...
) is also used as an earwax removal aid. Urea has also 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 Saline may refer to: * Saline (medicine), a liquid with salt content to match the human body * Saline water, non-medicinal salt water * Saline, a historical term (especially US) for a salt works or saltern Places * Saline, Calvados, a commune in ...
, urea has been injected into the uterus to induce abortion, although this method is no longer in widespread use. The
blood urea nitrogen Blood urea nitrogen (BUN) is a medical test that measures the amount of urea nitrogen found in blood. The liver produces urea in the urea cycle as a waste product of the digestion of protein. Normal human adult blood should contain 6 to 20 mg/dL ...
(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 Assessment of kidney function occurs in different ways, using the presence of symptoms and signs, as well as measurements using urine tests, blood tests, and medical imaging. Functions of a healthy kidney include maintaining a person's fluid ...
, 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 formulation to enhance local drug delivery to stenotic blood vessels. Urea, when used as an excipient in small doses (~3 μg/mm2) 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 Carbon-14, C-14, or radiocarbon, is a radioactive isotope of carbon with an atomic nucleus containing 6 protons and 8 neutrons. Its presence in organic materials is the basis of the radiocarbon dating method pioneered by Willard Libby and coll ...
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 The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms anterior intestine or proximal intestine m ...
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 uses

* 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 Emission may refer to: Chemical products * Emission of air pollutants, notably: **Flue gas, gas exiting to the atmosphere via a flue ** Exhaust gas, flue gas generated by fuel combustion ** Emission of greenhouse gases, which absorb and emit rad ...
into harmless nitrogen and water. *A component of
animal feed Animal feed is food given to domestic animals, especially livestock, in the course of animal husbandry. There are two basic types: fodder and forage. Used alone, the word ''feed'' more often refers to fodder. Animal feed is an important input to ...
, providing a relatively cheap source of 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
pretzel A pretzel (), from German pronunciation, standard german: Breze(l) ( and French / Alsatian: ''Bretzel'') is a type of baked bread made from dough that is commonly shaped into a knot. The traditional pretzel shape is a distinctive symmetrical ...
s * An ingredient in some skin cream, moisturizers,
hair conditioner Hair conditioner is a hair care cosmetic product used to improve the feel, texture, appearance, and manageability of hair. Its main purpose is to reduce friction between strands of hair to allow smoother brushing or combing, which might otherwise ...
s, and shampoos * A
cloud seeding Cloud seeding is a type of weather modification that aims to change the amount or type of precipitation that falls from clouds by dispersing substances into the air that serve as cloud condensation or ice nuclei, which alter the microphysical p ...
agent, along with other salts * A
flame-proofing agent Fireproofing is rendering something (structures, materials, etc.) resistant to fire, or incombustible; or material for use in making anything fire-proof. It is a passive fire protection measure. "Fireproof" or "fireproofing" can be used as a n ...
, commonly used in dry chemical fire extinguisher charges such as the urea- potassium bicarbonate mixture * An ingredient in many tooth whitening products * An ingredient in dish soap * Along with diammonium phosphate, as a yeast nutrient, for fermentation of
sugar Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. Compound sugars, also called disaccharides or double ...
s into ethanol * A nutrient used by plankton in
ocean nourishment Ocean fertilization or ocean nourishment is a type of technology for carbon dioxide removal from the ocean based on the purposeful introduction of plant nutrients to the upper ocean to increase marine food production and to remove carbon dioxid ...
experiments for
geoengineering Climate engineering (also called geoengineering) is a term used for both carbon dioxide removal (CDR) and solar radiation management (SRM), also called solar geoengineering, when applied at a planetary scale.IPCC (2022Chapter 1: Introduction and F ...
purposes * As an additive to extend the working temperature and open time of
hide glue Animal glue is an adhesive that is created by prolonged boiling of animal connective tissue in a process called rendering. In addition to being used as an adhesive it is used for coating and sizing, in decorative composition ornaments, and as a ...
* As a solubility-enhancing and moisture-retaining additive to
dye A dye is a colored substance that chemically bonds to the substrate to which it is being applied. This distinguishes dyes from pigments which do not chemically bind to the material they color. Dye is generally applied in an aqueous solution an ...
baths for textile dyeing or printing * As an optical parametric oscillator in nonlinear optics


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.
camel A camel (from: la, camelus and grc-gre, κάμηλος (''kamēlos'') from Hebrew or Phoenician: גָמָל ''gāmāl''.) is an even-toed ungulate in the genus ''Camelus'' that bears distinctive fatty deposits known as "humps" on its back. C ...
s, 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.


Physiology

Amino acids from ingested food that are used for the synthesis of proteins and other biological substances — or produced from catabolism of muscle protein — are 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 from protein into
metabolic waste Metabolic wastes or excrements are substances left over from metabolic processes (such as cellular respiration) which cannot be used by the organism (they are surplus or toxic), and must therefore be excreted. This includes nitrogen compounds, ...
in the liver is removal of the alpha-amino nitrogen, which results in 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 Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...
are converted to urea, while - ornithine, citrulline, -
argininosuccinate Argininosuccinic acid is a non-proteinogenic amino acid that is an important intermediate in the urea cycle. It is a basic amino acid. Reactions Some cells synthesize argininosuccinic acid from citrulline and aspartic acid and use it as a precur ...
, and -
arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...
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 Sodium chloride , commonly known as salt (although sea salt also contains other chemical salts), is an ionic compound with the chemical formula NaCl, representing a 1:1 ratio of sodium and chloride ions. With molar masses of 22.99 and 35.45 g ...
and water) in sweat. In water, the amine groups undergo slow displacement by water molecules, producing ammonia,
ammonium ion The ammonium cation is a positively-charged polyatomic ion with the chemical formula or . It is formed by the protonation of ammonia (). Ammonium is also a general name for positively charged or protonated substituted amines and quaternary a ...
, and
bicarbonate ion In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula . Bicarbonate serves a crucial biochemica ...
. 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 Countercurrent exchange is a mechanism occurring in nature and mimicked in industry and engineering, in which there is a crossover of some property, usually heat or some chemical, between two flowing bodies flowing in opposite directions to each ...
of the nephrons, that allows for reabsorption of water and critical ions from the excreted urine. Urea is reabsorbed in the
inner medullary collecting duct The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct system is the last part of nephron and participates in elect ...
s of the nephrons, Page 837 thus raising the osmolarity in the
medullary interstitium The renal medulla is the innermost part of the kidney. The renal medulla is split up into a number of sections, known as the renal pyramids. Blood enters into the kidney via the renal artery, which then splits up to form the segmental arteries whi ...
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 Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travel ...
, 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 Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...
, and maintain a suitable concentration of sodium ions in the blood plasma. The equivalent nitrogen content (in grams) of urea (in
mmol The mole, symbol mol, is the unit of amount of substance in the International System of Units (SI). The quantity amount of substance is a measure of how many elementary entities of a given substance are in an object or sample. The mole is define ...
) can be estimated by the conversion factor 0.028 g/mmol. Furthermore, 1 gram of nitrogen is roughly equivalent to 6.25 grams of protein, and 1 gram of protein is roughly equivalent to 5 grams of
muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
tissue. In situations such as muscle wasting, 1 mmol 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 0.67 gram.


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
mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
s and
amphibian Amphibians are tetrapod, four-limbed and ectothermic vertebrates of the Class (biology), class Amphibia. All living amphibians belong to the group Lissamphibia. They inhabit a wide variety of habitats, with most species living within terres ...
s, as well as some fish. Birds and
saurian Sauria is the clade containing the most recent common ancestor of archosaurs (such as crocodilians, dinosaurs, etc.) and lepidosaurs ( lizards and kin), and all its descendants. Since most molecular phylogenies recover turtles as more closel ...
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 Metamorphosis is a biological process by which an animal physically develops including birth or hatching, involving a conspicuous and relatively abrupt change in the animal's body structure through cell growth and differentiation. Some inse ...
. 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.


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

Ureas describes a ''class'' of chemical compounds that share the same functional group, a carbonyl group attached to two organic amine residues: , where groups are hydrogen (–H),
organyl In organic and organometallic chemistry, an organyl group is an organic substituent with one (sometimes more) free valence(-s) at a carbon atom.. The term is often used in chemical patent literature to protect claims over a broad scope. Examples ...
or other groups. Examples include
carbamide peroxide Hydrogen peroxide - urea (also called Hyperol, artizone, urea hydrogen peroxide, and UHP) is a solid composed of equal amounts of hydrogen peroxide and urea. This compound is a white crystalline solid which dissolves in water to give free hydrogen ...
, allantoin, and
hydantoin Hydantoin, or glycolylurea, is a heterocyclic organic compound with the formula CH2C(O)NHC(O)NH. It is a colorless solid that arises from the reaction of glycolic acid and urea. It is an oxidized derivative of imidazolidine. In a more general sen ...
. Ureas are closely related to
biuret Biuret is a chemical compound with the chemical formula . It is a white solid that is soluble in hot water. A variety of organic derivatives are known. The term "biuret" also describes a family of organic compounds with the chemical formula , where ...
s and related in structure to amides,
carbamate In organic chemistry, a carbamate is a category of organic compounds with the general formula and structure , which are formally derived from carbamic acid (). The term includes organic compounds (e.g., the ester ethyl carbamate), formally o ...
s, carbodiimides, and
thiocarbamide Thiourea () is an organosulfur compound with the formula and the structure . It is structurally similar to urea (), except that the oxygen atom is replaced by a sulfur atom (as implied by the ''thio-'' prefix); however, the properties of urea a ...
s.


History

Urea was first discovered in urine in 1727 by the Dutch scientist Herman Boerhaave, although this discovery is often attributed to the
French French (french: français(e), link=no) may refer to: * Something of, from, or related to France ** French language, which originated in France, and its various dialects and accents ** French people, a nation and ethnic group identified with Franc ...
chemist
Hilaire Rouelle Hilaire Marin Rouelle (15 February 1718 – 7 April 1779) was an 18th-century French chemist. Commonly cited as the 1773 discoverer of urea, he was not the first to do so. Dutch scientist Herman Boerhaave had discovered this chemical A chem ...
as well as William Cruickshank. Boerhaave used the following steps to isolate urea: #Boiled off water, resulting in a substance similar to fresh cream #Used filter paper to squeeze out remaining liquid #Waited a year for solid to form under an oily liquid #Removed the oily liquid #Dissolved the solid in water #Used recrystallization to tease out the urea In 1828, the
German German(s) may refer to: * Germany (of or related to) **Germania (historical use) * Germans, citizens of Germany, people of German ancestry, or native speakers of the German language ** For citizens of Germany, see also German nationality law **Ger ...
chemist
Friedrich Wöhler Friedrich Wöhler () FRS(For) HonFRSE (31 July 180023 September 1882) was a German chemist known for his work in inorganic chemistry, being the first to isolate the chemical elements beryllium and yttrium in pure metallic form. He was the firs ...
obtained urea artificially by treating silver cyanate with ammonium chloride. : This was the first time an organic compound was artificially synthesized from inorganic starting materials, without the involvement of living organisms. The results of this experiment implicitly discredited
vitalism Vitalism is a belief that starts from the premise that "living organisms are fundamentally different from non-living entities because they contain some non-physical element or are governed by different principles than are inanimate things." Wher ...
, 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: :"''I must tell you that I can make urea without the use of kidneys, either man or dog. Ammonium cyanate is urea.''" In fact, 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. Regardless, with his discovery, Wöhler secured a place among the pioneers of organic chemistry.


Production

Urea is produced on an industrial scale: In 2012, worldwide production capacity was approximately 184 million tonnes.


Industrial methods

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 from hydrocarbons (predominantly natural gas, less often petroleum derivatives), or occasionally from coal (
water shift reaction Water (chemical formula ) is an Inorganic compound, inorganic, transparent, tasteless, odorless, and Color of water, nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living ...
), urea production plants are almost always located adjacent to the site where the ammonia is manufactured. Although natural gas is both the most economical and the most widely available ammonia plant feedstock, plants using it do not produce quite as much carbon dioxide from the process as is needed to convert their entire ammonia output into urea. In recent years new technologies such as the KM-CDR process have been developed to recover supplementary carbon dioxide from the combustion exhaust gases produced in the fired reforming furnace of the ammonia synthesis gas plant, allowing operators of stand-alone nitrogen fertilizer complexes to avoid the need to handle and market ammonia as a separate product and also to reduce their greenhouse gas emissions to the atmosphere.


Synthesis

The basic process, developed in 1922, is also called the Bosch–Meiser urea process after its discoverers. Various commercial urea processes are characterized by the conditions under which urea forms and the way that unconverted reactants are further processed. The process consists of two main equilibrium reactions, with incomplete conversion of the reactants. The first is carbamate formation: the fast
exothermic In thermodynamics, an exothermic process () is a thermodynamic process or reaction that releases energy from the system to its surroundings, usually in the form of heat, but also in a form of light (e.g. a spark, flame, or flash), electricity (e ...
reaction of liquid ammonia with gaseous carbon dioxide () at high temperature and pressure to form
ammonium carbamate Ammonium carbamate is a chemical compound with the formula consisting of ammonium cation and carbamate anion . It is a white solid that is extremely soluble in water, less so in alcohol. Ammonium carbamate can be formed by the reaction of ammo ...
(): : (Δ''H'' = −117 kJ/mol at 110 atm and 160 °C) The second is urea conversion: the slower endothermic decomposition of ammonium carbamate into urea and water: : (Δ''H'' = +15.5 kJ/mol at 160–180 °C) The overall conversion of and to urea is exothermic, the reaction heat from the first reaction driving the second. Like all chemical equilibria, these reactions behave according to
Le Chatelier's principle Le Chatelier's principle (pronounced or ), also called Chatelier's principle (or the Equilibrium Law), is a principle of chemistry used to predict the effect of a change in conditions on chemical equilibria. The principle is named after French c ...
, and the conditions that most favour carbamate formation have an unfavourable effect on the urea conversion equilibrium. The process conditions are, therefore, a compromise: the ill-effect on the first reaction of the high temperature (around 190 °C) needed for the second is compensated for by conducting the process under high pressure (140–175 bar), which favours the first reaction. Although it is necessary to compress gaseous carbon dioxide to this pressure, the ammonia is available from the ammonia plant in liquid form, which can be pumped into the system much more economically. To allow the slow urea formation reaction time to reach equilibrium a large reaction space is needed, so the synthesis reactor in a large urea plant tends to be a massive pressure vessel. Because the urea conversion is incomplete, the product must be separated from unchanged ammonium carbamate. In early "straight-through" urea plants this was done by letting down the system pressure to atmospheric to let the carbamate decompose back to ammonia and carbon dioxide. Originally, because it was not economic to recompress the ammonia and carbon dioxide for recycle, the ammonia at least would be used for the manufacture of other products, for example ammonium nitrate or sulfate. (The carbon dioxide was usually wasted.) Later process schemes made recycling unused ammonia and carbon dioxide practical. This was accomplished by depressurizing the reaction solution in stages (first to 18 – 25 bar and then to 2 – 5 bar) and passing it at each stage through a steam-heated ''carbamate decomposer'', then recombining the resultant carbon dioxide and ammonia in a falling-film ''carbamate condenser'' and pumping the carbamate solution into the previous stage.


= Stripping concept

= The "total recycle" concept has two main disadvantages. The first is the complexity of the flow scheme and, consequently, the amount of process equipment needed. The second is the amount of water recycled in the carbamate solution, which has an adverse effect on the equilibrium in the urea conversion reaction and thus on overall plant efficiency. The stripping concept, developed in the early 1960s by
Stamicarbon Stamicarbon is the licensing and IP center of Maire Tecnimont SpA which licenses technology for manufacturing urea as well as provide follow-up services designed to ensure the best possible operation of the urea plant throughout its working life. ...
in The Netherlands, addressed both problems. It also improved heat recovery and reuse in the process. The position of the equilibrium in the carbamate formation/decomposition depends on the product of the
partial pressure In a mixture of gases, each constituent gas has a partial pressure which is the notional pressure of that constituent gas as if it alone occupied the entire volume of the original mixture at the same temperature. The total pressure of an ideal gas ...
s of the reactants. In the total recycle processes, carbamate decomposition is promoted by reducing the overall pressure, which reduces the partial pressure of both ammonia and carbon dioxide. It is possible, however, to achieve a similar effect without lowering the overall pressure—by suppressing the partial pressure of just one of the reactants. Instead of feeding carbon dioxide gas directly to the reactor with the ammonia, as in the total recycle process, the stripping process first routes the carbon dioxide through a stripper (a carbamate decomposer that operates under full system pressure and is configured to provide maximum 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 passes directly to the reactor. That eliminates the medium-pressure stage of the total recycle process altogether. The stripping concept was such a major advance that competitors such as Snamprogetti — now Saipem — (Italy), the former
Montedison Edison S.p.A. is an Italian electric utility company headquartered in Milan. The company was established in 1884 and acquired by Electricité de France in 2012. Edison employs more than 5,000 people in Europe, North Africa and the Middle East. C ...
(Italy), Toyo Engineering Corporation (Japan), and
Urea Casale Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two Amine, amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an impor ...
(Switzerland) all developed versions of it. Today, effectively all new urea plants use the principle, and many total recycle urea plants have converted to a stripping process. No one has proposed a radical alternative to the approach. The main thrust of technological development today, in response to industry demands for ever larger individual plants, is directed at re-configuring and re-orientating major items in the plant to reduce size and overall height of the plant, and at meeting challenging environmental performance targets.


= Side reactions

= It is fortunate that the urea conversion reaction is slow. If it were not it would go into reverse in the stripper. As it is, succeeding stages of the process must be designed to minimize residence times, at least until the temperature reduces to the point where the reversion reaction is very slow. Two reactions produce impurities.
Biuret Biuret is a chemical compound with the chemical formula . It is a white solid that is soluble in hot water. A variety of organic derivatives are known. The term "biuret" also describes a family of organic compounds with the chemical formula , where ...
is formed when two molecules of urea combine with the loss of a molecule of ammonia. : Normally this reaction is suppressed in the synthesis reactor by maintaining an excess of ammonia, but after the stripper, it occurs until the temperature is reduced. Biuret is undesirable in fertilizer urea because it is toxic to crop plants, although to what extent depends on the nature of the crop and the method of application of the urea. (Biuret is actually welcome in urea when is used as a cattle feed supplement).
Isocyanic acid Isocyanic acid is a chemical compound with the structural formula HNCO, which is often written as . It is a colourless, volatile and poisonous substance, with a boiling point of 23.5 °C. It is the predominant tautomer of cyanic acid (). ...
HNCO and ammonia results from the thermal decomposition of ammonium cyanate , which is in chemical equilibrium with urea: : This reaction 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.


= Corrosion

=
Ammonium carbamate Ammonium carbamate is a chemical compound with the formula consisting of ammonium cation and carbamate anion . It is a white solid that is extremely soluble in water, less so in alcohol. Ammonium carbamate can be formed by the reaction of ammo ...
solutions are notoriously corrosive to metallic construction materials, even more resistant forms of
stainless steel Stainless steel is an alloy of iron that is resistant to rusting and corrosion. It contains at least 11% chromium and may contain elements such as carbon, other nonmetals and metals to obtain other desired properties. Stainless steel's corros ...
– especially in the hottest parts of the plant such as the stripper. Historically corrosion has been minimized (although not eliminated) by continuous injection of a small amount of oxygen (as air) into the plant to establish and maintain a passive oxide layer on exposed stainless steel surfaces. Because the carbon dioxide feed is recovered from ammonia synthesis gas, it contains traces of hydrogen that can mingle with passivation air to form an
explosive An explosive (or explosive material) is a reactive substance that contains a great amount of potential energy that can produce an explosion if released suddenly, usually accompanied by the production of light, heat, sound, and pressure. An expl ...
mixture if allowed to accumulate. In the mid 1990s two duplex (ferritic-austenitic) stainless steels were introduced (DP28W, jointly developed by
Toyo Engineering is a Japanese engineering, procurement and construction company serving mainly the hydrocarbons (oil and natural gas) and petrochemical sectors worldwide. It was established in 1961. Its various business include R&D collaboration, design, engine ...
and
Sumitomo Metals Industries was a steel manufacturer based in Osaka, Japan until it merged with Nippon Steel in 2012 to form Nippon Steel & Sumitomo Metal Corporation, the third largest steel manufacturer in the world as of 2015. Its origins as a modern company date from 189 ...
and Safurex, jointly developed by
Stamicarbon Stamicarbon is the licensing and IP center of Maire Tecnimont SpA which licenses technology for manufacturing urea as well as provide follow-up services designed to ensure the best possible operation of the urea plant throughout its working life. ...
and Sandvik Materials Technology (Sweden).) These let manufactures drastically reduce the amount of passivation oxygen. In theory, they could operate with no oxygen. Saipem now uses either zirconium stripper tubes, or bimetallic tubes with a titanium body (cheaper but less erosion-resistant) and a metallurgically bonded internal zirconium lining. These tubes are fabricated by
ATI Wah Chang Wah Chang Corporation was an American manufacturing company in the metal or alloy industry based in Albany, Oregon in the United States. Since 2014, it is a business unit of ATI. History In 1916 (some sources say 1914), Chinese American mining ...
(USA) using its Omegabond technique.


Finishing

Urea can be produced as prills, granules, pellets, crystals, and solutions.


= Solid forms

= For its main use as a fertilizer urea is mostly marketed in solid form, either as prills or granules. The advantage of prills is that, in general, they can be produced more cheaply than granules and that the technique was firmly established in industrial practice long before a satisfactory urea granulation process was commercialized. However, on account of the limited size of particles that can be produced with the desired degree of sphericity and their low crushing and impact strength, the performance of prills during bulk storage, handling and use is generally (with some exceptions) considered inferior to that of granules. High-quality compound fertilizers containing nitrogen co-granulated with other components such as phosphates have been produced routinely since the beginnings of the modern fertilizer industry, but on account of the low melting point and hygroscopic nature of urea it took courage to apply the same kind of technology to granulate urea on its own. But at the end of the 1970s three companies began to develop
fluidized-bed A fluidized bed is a physical phenomenon that occurs when a solid particulate substance (usually present in a holding vessel) is under the right conditions so that it behaves like a fluid. The usual way to achieve a fluidize bed is to pump pressu ...
granulation.


= UAN solutions

= In admixture, the combined solubility of ammonium nitrate and urea is so much higher than that of either component alone that it is possible to obtain a stable solution (known as UAN) with a total nitrogen content (32%) approaching that of solid ammonium nitrate (33.5%), though not, of course, that of urea itself (46%). Given the ongoing safety and security concerns surrounding fertilizer-grade solid ammonium nitrate, UAN provides a considerably safer alternative without entirely sacrificing the agronomic properties that make ammonium nitrate more attractive than urea as a fertilizer in areas with short growing seasons. It is also more convenient to store and handle than a solid product and easier to apply accurately to the land by mechanical means.


Laboratory preparation

Ureas in the more general sense can be accessed in the laboratory by reaction of
phosgene Phosgene is the organic chemical compound with the formula COCl2. It is a toxic, colorless gas; in low concentrations, its musty odor resembles that of freshly cut hay or grass. Phosgene is a valued and important industrial building block, espe ...
with primary or secondary amines: : These reactions proceed through an isocyanate intermediate. Non-symmetric ureas can be accessed by the reaction of primary or secondary amines with an isocyanate. Urea can also be produced by heating ammonium cyanate to 60 °C. :


Historical process

Urea was first noticed by Herman Boerhaave in the early 18th century from evaporates of urine. In 1773,
Hilaire Rouelle Hilaire Marin Rouelle (15 February 1718 – 7 April 1779) was an 18th-century French chemist. Commonly cited as the 1773 discoverer of urea, he was not the first to do so. Dutch scientist Herman Boerhaave had discovered this chemical A chem ...
obtained crystals containing urea from human urine by evaporating it and treating it with alcohol in successive filtrations. This method was aided by Carl Wilhelm Scheele's discovery that urine treated by concentrated nitric acid precipitated crystals.
Antoine François, comte de Fourcroy Antoine is a French given name (from the Latin ''Antonius'' meaning 'highly praise-worthy') that is a variant of Danton, Titouan, D'Anton and Antonin. The name is used in France, Switzerland, Belgium, Canada, West Greenland, Haiti, French Guiana ...
and Louis Nicolas Vauquelin discovered in 1799 that the nitrated crystals were identical to Rouelle's substance and invented the term "urea." Berzelius made further improvements to its purification and finally William Prout, in 1817, succeeded in obtaining and determining the chemical composition of the pure substance. 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.


Properties


Molecular and crystal structure

The urea molecule is planar. In solid urea, the oxygen center is engaged in two N–H–O
hydrogen bond In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...
s. The resulting dense and energetically favourable 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 sp2 hybridized, the C-N bonds have significant double bond character, and the carbonyl oxygen is basic compared to, say, formaldehyde. 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. This behaviour can be used to separate mixtures, e.g., in the production of
aviation fuel Aviation fuels are petroleum-based fuels, or petroleum and synthetic fuel blends, used to power aircraft. They have more stringent requirements than fuels used for ground use, such as heating and road transport, and contain additives to enhanc ...
and
lubricating oil A lubricant (sometimes shortened to lube) is a substance that helps to reduce friction between surfaces in mutual contact, which ultimately reduces the heat generated when the surfaces move. It may also have the function of transmitting forces, t ...
s, and in the separation of hydrocarbons. As the
helices A helix () is a shape like a corkscrew or spiral staircase. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is formed as two intertwined helices, ...
are interconnected, all helices in a crystal must have the same molecular handedness. This is determined when the crystal is nucleated and can thus be forced by seeding. The resulting crystals have been used to separate
racemic mixture In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...
s.


Reactions

Urea is basic. As such it is protonates readily. It is also a
Lewis base A Lewis acid (named for the American physical chemist Gilbert N. Lewis) is a chemical species that contains an empty orbital which is capable of accepting an electron pair from a Lewis base to form a Lewis adduct. A Lewis base, then, is any sp ...
forming complexes of the type . Molten urea decomposes into ammonia gas and
isocyanic acid Isocyanic acid is a chemical compound with the structural formula HNCO, which is often written as . It is a colourless, volatile and poisonous substance, with a boiling point of 23.5 °C. It is the predominant tautomer of cyanic acid (). ...
: : Via isocyanic acid, heating urea converts to a range of condensation products including
biuret Biuret is a chemical compound with the chemical formula . It is a white solid that is soluble in hot water. A variety of organic derivatives are known. The term "biuret" also describes a family of organic compounds with the chemical formula , where ...
,
triuret Triuret is an organic compound with the formula (H2NC(O)NH)2CO. It is a product from the pyrolysis of urea. Triuret is a colorless, crystalline, hygroscopic solid, slightly soluble in cold water or ether, and more soluble in hot water. It is a p ...
, guanidine , and melamine: : : In aqueous solution, urea slowly equilibrates with ammonium cyanate. This hydrolysis cogenerates
isocyanic acid Isocyanic acid is a chemical compound with the structural formula HNCO, which is often written as . It is a colourless, volatile and poisonous substance, with a boiling point of 23.5 °C. It is the predominant tautomer of cyanic acid (). ...
, which can carbamylate proteins. Urea reacts with malonic esters to make barbituric acids. Urea may be use for obtaining deep eutectic solvents with sulfamic acidKazachenko, Aleksandr S.; Issaoui, Noureddine; Medimagh, Mouna ; Yu. Fetisova, Olga; Berezhnaya, Yaroslava D.; Elsuf'ev, Evgeniy V.; Al-Dossary, Omar M.; Wojcik, Marek J.; Xiang, Zhouyang; Bousiakou, Leda G. Experimental and theoretical study of the sulfamic acid-urea deep eutectic solvent. (2022) Journal of Molecular Liquids, 363, art. no. 119859. DOI: 10.1016/j.molliq.2022.119859


Etymology

''Urea'' is New Latin, from French , from Ancient Greek (''ouron'', "urine"), itself from Proto-Indo-European ''*h₂worsom''.


See also

* Wöhler urea synthesis * Thiourea


References


External links

* {{Authority control Nitrogen cycle Functional groups Excretion Soil improvers Fertilizers Urea cycle Lymph fluid Commodity chemicals Household chemicals E-number additives Organic compounds with 1 carbon atom