57-13-6

Basic information

• Product Name: Urea
• Synonyms: aquacare;Aquacare HP;aquacarehp;Aquadrate;Aqua-drate;Basodexan;Benural 70;B-I-K
• CAS NO: 57-13-6
• Molecular Formula: CH₄N₂O
• Molecular Weight: 60.06
• EINECS: 200-315-5
• Product Categories: Enzymes;Alphabetical Listings;Stable Isotopes;U-Z;Chaotropic Agents;Bioactive Small Molecules;Biochemicals and Reagents;Building Blocks;Carbonyl Compounds;Cell Biology;Chemical Synthesis;Denaturation;Organic Building Blocks;U;Ureas;Protein Electrophoresis;Proteomics;SDS-PAGE;Urea;fertilizer;ACTIGALL;proteinmod;Inhibitors;Industrial Grade;Food Additive
• Mol File: 57-13-6.mol
• Article Data: 168

Chemical Properties

• Melting Point: 132-135 °C(lit.)
• Boiling Point: 332.48°C (estimate)
• Flash Point: 72.708 °C
• Appearance: white/powder
• Density: 1.335 g/mL at 25 °C(lit.)
• Vapor Pressure: <0.1 hPa (20 °C)
• Refractive Index: n20/D 1.40
• Storage Temp.: 2-8°C
• Solubility: H2O: 8 M at 20 °C
• PKA: 0.10(at 25℃)
• Water Solubility: 1080 g/L (20 ºC)
• Stability: Substances to be avoided include strong oxidizing agents. Protect from moisture.
• Merck: 14,9867
• BRN: 635724
• CAS DataBase Reference: Urea(CAS DataBase Reference)
• NIST Chemistry Reference: Urea(57-13-6)
• EPA Substance Registry System: Urea(57-13-6)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 36/37/38-40-38
• Safety Statements: 26-36-24/25-37
• RIDADR: Not regulated
• WGK Germany: 1
• RTECS: YR6250000
• TSCA: Yes
• Hazardous Substances Data: 57-13-6(Hazardous Substances Data)

Usage

Chemical structure

Lewis structure Ball-and-stick diagram Space-filling model Urea, also known as carbamide, is an organic compound with chemical formula CO (NH2)2. This amide has two –NH2 groups joined by a carbonyl (C=O) functional group.

History

Different sources of media describe the History of 57-13-6 differently. You can refer to the following data:
1. Pure urea was first isolated from urine in 1727 by the Dutch scientist Herman Boerhaave, and he extracted urea from urine by working with the concentated-by-boiling residue. But if only not considering the purity of urea, the discovery of urea should be attributed to the French chemist Hilaire Rouelle, and he prepared urea (or its addition compound with sodium chloride) from urine some time before 1727. In 1828, just 55 years after its discovery, urea became the first organic compound to be synthetically formulated, this time by a German chemist named Friedrich W?hler, one of the pioneers of organic chemistry. It was found when Wohler attempted to synthesis ammonium cyanate, to continue a study of cyanates which he had been carrying out for several years. On treating silver cyanate with ammonium chloride solution he obtained a white crystalline material which proved identical to urea obtained from urine. AgNCO + NH4Cl → (NH2)2CO + AgCl Synthetic urea is created from synthetic ammonia and carbon dioxide and can be produced as a liquid or a solid. The process of dehydrating ammonium carbamate under conditions of high heat and pressure to produce urea was first implemented in 1870 and is still in use today. Uses of synthetic urea are numerous and therefore production is high. Approximately one million pounds of urea is manufactured in the United States alone each year, most of it used in fertilizers. Nitrogen in urea makes it water soluble, a highly desired property in this application.
2. Urea has the distinction of being the first synthesized organic compound. Until the mid-18th century, scientists believed organic compounds came only from live plants and animals. The first serious blow to the theory of vitalism, which marked the beginning of modern organic chemistry, occurred when Friedrich W?hler (1800 1882) synthesized urea from the two inorganic substances, lead cyanate and ammonium hydroxide: Pb(OCN)2 + 2NH4OH→2(NH2)2CO + Pb(OH)2. W?hler's discoveries on urea occurred while he was studying cyanates; he was attempting to synthesize ammonium cyanate when he discovered crystals of urea in his samples. He first prepared urea in 1824, but he did not identify this product and report his findings until 1828. W?hler's synthesis of urea signaled the birth of organic chemistry.

Occurrence

Different sources of media describe the Occurrence of 57-13-6 differently. You can refer to the following data:
1. Urea is the chief nitrogenous end product of the metabolic breakdown of proteins in all mammals and some fishes. The material occurs not only in the urine of all mammals but also in their blood, bile, milk, and perspiration. In the course of the breakdown of proteins, amino groups (NH2) are removed from the amino acids that partly comprise proteins. These amino groups are converted to ammonia (NH3), which is toxic to the body and thus must be converted to urea by the liver. The urea then passes to the kidneys and is eventually excreted in the urine. Fig.1 The urea cycle in animals
2. The compound was discovered by Hilaire Rouelle in 1773 as a constituent of urine.

Physical properties

Fig.2 Urea crystal It is a colourless, crystalline substance that melts at 132.7°C (271°F) and decomposes before boiling. Its density is 1.32 g/cm3 and It is highly soluble in water and contains 46.7% nitrogen.

Chemical Properties

Different sources of media describe the Chemical Properties of 57-13-6 differently. You can refer to the following data:
1. The urea molecule is planar in the crystal structure, but the geometry around the nitrogens is pyramidal in the gas-phase minimum-energy structure. In solid urea, the oxygen center is engaged in two N-H-O hydrogen bonds. 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. Urea dissolved in water is in equilibrium with the isomeric ammonium cyanate. The resulting activity of the isocyanic acid ions do result in carbamylation (formation of long-chain carbamides, liberating ammonia molecule as byproduct) of proteins if proteins are present in the solution too. The carbamylation reaction may occurs at elevated temperatures even without catalysts. At room temperature, water solutions of urea are prone to same decomposition reaction in the presence of urease. The isomerization of urea in solution at room temperature without catalysts is a slow process (taking days to reach equilibrium), and freshly prepared, unheated solutions had negligible carbamylation rates.Urea can react with alcohols to form urethanes and react with malonic esters to make barbituric acids.
2. Urea,CO(HN2)2, also known as carbamide, is a white crystalline powder that has a melting point of l32.7 °C (270 °F). It is a natural product of animal protein metabolism and is the chief nitrogen constituent of urine. Commercially, urea is produced by the reaction of ammonia and carbon dioxide. It is soluble in water, alcohol, and benzene.
3. Urea is a white crystalline so lid.

Productions

The primary raw material used to manufacture urea is natural gas, which ties the costs directly to gas prices. Consequently, new plants are only being built in areas with large natural gas reserves where prices are lower. Finished product is transported around the globe in large shipments of 30,000 metric tons. The market price for urea is directly related to the world price of natural gas and the demand for agricultural products. Prices can be very volatile, and at times, unpredictable. TCC is positioned to know the world markets and keep your prices competitive. Annual production of sulfuric acid ▼▲ World 164 million tonnes China 62 million tonnes India 23 million tonnes Middle East 20 million tonnes Rest of Asia 18 million tonnes FSU 12 million tonnes North America 9.5 million tonnes Europe 9.5 million tonnes It is expected that the global annual production will increase to over 200 million tonnes by 2018. 1. Potash Corporation, 2013 2. International Fertilizer Industry Association, 2014

Production methods

Historical process Urea was first noticed by Hermann Boerhaave in the early 18th century from evaporates of urine. In 1773, Hilaire Rouelle 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 Fran?ois, 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 made further improvements to its purificationand 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. Industrial process 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, urea production plants are almost always located adjacent to the site where the ammonia is manufactured. Urea can be produced as prills, granules, pellets, crystals, and solutions. The prills are formed by spraying molten urea down a tower up which air is pumped. They are slightly smaller than urea sold as granules and are particularly useful when the fertilizer is being applied by hand. 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%). Fig.3 Industrial process of urea Fig.4 An aerial view of a large plant in Alberta, Canada, in which ammonia is synthesized and then converted to urea.( By kind permission of Agrium Inc.) Fig.5 Prills(small spheres of urea) Fig.6 UAN(admixture of urea and ammonium nitrate) Laboratory process Ureas in the more general sense can be accessed in the laboratory by reaction of phosgene with primary or secondary amines, proceeding through an isocyanate intermediate. Non-symmetric ureas can be accessed by reaction of primary or secondary amines with an isocyanate. Also, urea is produced when phosgene reacts with ammonia: COCl2 + 4 NH3 → (NH2)2CO + 2 NH4Cl Urea is byproduct of converting alkyl halides to thiols via a S-alkylation of thiourea. Such reactions proceed via the intermediacy of isothiouronium salts: RX + CS(NH2)2 → RSCX(NH2)2X RSCX(NH2)2X + MOH → RSH + (NH2)2CO + MX In this reaction R is alkyl group, X is halogen and M is alkali metal.

Uses

Different sources of media describe the Uses of 57-13-6 differently. You can refer to the following data:
1. Agriculture uses 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 the lowest transportation costs per unit of nitrogen nutrient. In the soil, it hydrolyses back to ammonia and carbon dioxide. The ammonia is oxidized by bacteria in the soil to nitrate, which can be absorbed by the plants. Urea is also used in many multi-component solid fertilizer formulations. Urea is highly soluble in water, therefore, very suitable for use in fertilizer solutions (in combination with ammonium nitrate: UAN), e.g., in ‘foliar feed’ fertilizers. For fertilizer use, granules are preferred because of their narrower particle size distribution, an advantage for mechanical application. The most common impurity of synthetic urea, biuret, must be present at less than 2 percent of the time, as it impairs plant growth. Fig.7 Urea fertilizer and farmer’s fertilization process Pharmacaeutical Urea and malonic acid react to form barbituric acid. This was discovered by Adolf Bayer in 1864. But the barbiturates were not exploited as hypnotics until the early 1900's.Urea is also used in the production of various acylureas and urethanes for use as sedatives and hypnotics. Fig.8 Synthesis of barbituric acid Chemical industry Urea is a raw material for the manufacture of two main classes of materials: urea-formaldehyde resins and urea-melamine-formaldehyde used in marine plywood. They all have very varied uses including adhesives, laminates, moulding compounds, coatings and textile finishes. Urea has the ability to trap many organic compounds in the form of clathrates. The organic compounds are held in channels formed by interpenetrating helices comprising of hydrogen-bonded urea molecules. This behavior can be used to separate mixtures, and has been used in the production of aviation fuel and lubricating oils, and in the separation of paraffin. As the 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 mixtures. 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 is used as a deep eutectic solvent, a type of ionic liquid. Urea can in principle serve as a hydrogen source for subsequent power generation in fuel cells. 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 (0.37 V) and thus consumes less energy than the electrolysis of water (1.2 V). 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. Automobile systems Urea is used in SNCR and SCR reactions to reduce the NOx pollutants in exhaust gases from combustion, for example, from power plants and diesel engines. The BlueTec system, for example, injects water-based urea solution into the exhaust system. The ammonia produced by decomposition of the urea reacts with the nitrogen oxide emissions and is converted into nitrogen and water within the catalytic converter. Fig.9 A line diagram of the car above illustrating five key elements in the design of the exhaust system. 1 The oxidation catalyst is used to remove unwanted hydrocarbons, ensuring that they are oxidised to carbon dioxide and water. The catalyst is usually based on platinum or palladium. 2 Known as an NOx catalytic convertor, it contains aluminium oxide on whose surface, platinum and barium oxide are present. It traps the oxides of nitrogen. When the solid is saturated with the oxides, unburnt hydrocarbons are allowed to flow through, converting much of the mixture to nitrogen, carbon dioxide and water vapour. 3 A filter which traps particulates (small pieces of carbon and other solids). 4 A tank containing the solution of urea. 5 The SCR-catalytic convertor which contains another catalyst, for example an oxide of vanadium (or tungsten) on titanium dioxide, which allows the exhaust gases, still containing some nitrogen oxides, to react with ammonia formed from the urea solution, to produce exhaust gases with only traces of the oxides. By kind permission of Daimler AG Others A stabilizer in nitrocellulose explosive A component of animal feed, providing a relatively cheap source of nitrogen to promote growth A non-corroding alternative to rock salt for road de-icing, and the resurfacing of snowboarding half pipes and terrain parks A flavor-enhancing additive for cigarettes A main ingredient in hair removers such as Nair or Veet A browning agent in factory-produced pretzels An ingredient in some hair conditioners, facial cleansers, bath oils, skin softeners, and lotions A reactant in some ready-to-use cold compresses for first-aid use, due to the endothermic reaction it creates when mixed with water 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. An ingredient in many tooth whitening products An ingredient in dish soap Along with ammonium phosphate, as a yeast nutrient, for fermentation of sugars into ethanol A nutrient used by plankton in ocean nourishment experiments for geoengineering 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
2. The primary use of urea is as a nitrogen source in fertilizers, with about 90% of the urea production being used for this purpose. Urea's high nitrogen content (46%) makes it a concentrated source for adding fixed nitrogen to soils. It can be applied to the soil alone, but its high nitrogen content can stress plants and impact the soil negatively, so it is often blended with other nutrients. Blending also reduces the nitrogen content of the fertilizer. For example, blending with ammonium nitrate, NH4NO3, in different proportions produces fertilizers with various nitrogen contents. Urea in the soil is converted to ammonium nitrogen and taken up by plants. It can be applied in solid granule form or dissolved in water and used as a spray. Urea is also used agriculturally as a supplement in livestock feeds to assist protein synthesis.Another use of urea is for resins, which are used in numerous applications including plastics, adhesives, moldings, laminates, plywood, particleboard, textiles, and coatings. Resins are organic liquid substances exuded from plants that harden on exposure to air. The term now includes numerous synthetically produced resins. Urea resins are thermosetting, which means they harden when heated, often with the aid of a catalyst. The polymerization of urea and formaldehyde produces urea-formaldehyde resins, which is the second most abundant use of urea. Urea is dehydrated to melamine, which, when combined with formaldehyde, produces melamine-formaldehyde resins.
3. urea is incorporated into cosmetics for a variety of purposes, including moisturizing, desquamating, anti-microbial, and buffering. urea is regarded as a “true” moisturizer rather than a humectant because it attracts and retains moisture in the corneum layer. It facilitates the natural exfoliation of keratinocytes given its ability to dissolve intercellular cement in the corneum layer. Through its anti-microbial properties that inhibit the growth of micro-organisms in a product, urea can also be part of a larger preservative system. This ingredient’s buffering action is attributed to its ability to regulate the hydrolipid mantle. In addition, urea is found to enhance the penetration and absorption of other active ingredients, relieve itchiness, and help leave the skin feeling soft and supple. Anti-inflammatory, anti-septic, and deodorizing actions allow it to protect the skin’s surface against negative changes and help maintain healthy skin. Studies show that urea does not induce photoallergy, phototoxicity, or sensitization. The safest concentration of use in skin care preparations is between 2 and 8 percent. High concentrations of urea seem to be unstable when incorporated into skin care preparations and can also cause irritation. Acidic urea solutions can produce burning or stinging sensations.
4. Used for the denaturation of proteins and as a mild solubilization agent for insoluble or denatured proteins. Useful for renaturing proteins from samples already denatured with 6 M guanidine chloride such as inclusion bodies. May be used with guanidine hydrochloride and dithiothreitrol (DTT) in the refolding of denatured proteins into their native or active form.
5. anticholelithogenic; LD50(rat) 890 mg/kg ip
6. Urea is a physiological regulator of nitrogen excretion in mammals; synthesized in the liver as an end-product of protein catabolism and excreted in urine. Also occurs normally in skin. Emollient; diu retic.
7. 1) UREA, FCC is an odorless and colorless solid that is an important nitrogen-containing substance found in mammal urine.2) Urea has little or no nutritional value to monogastric mammals but Urea is used in sugar-free chewing gum to adjust the texture

Hazards

Health hazards Inhalation:? Causes irritation to the respiratory tract. Symptoms may include coughing, shortness of breath. May be absorbed into the bloodstream with symptoms similar to ingestion.? Ingestion:? Causes irritation to the gastrointestinal tract. Symptoms may include nausea, vomiting and diarrhea. May also cause headache, confusion and electrolyte depletion.? Skin Contact:? Causes irritation to skin. Symptoms include redness, itching, and pain.? Eye Contact:? Causes irritation, redness, and pain.? Chronic Exposure:? A study of 67 workers in an environment with high airborne concentrations of urea found a high incidence of protein metabolism disturbances, moderate emphysema, and chronic weight loss.? Aggravation of Pre-existing Conditions:? Supersensitive individuals with skin or eye problems, kidney impairment or asthmatic condition should have physician's approval before exposure to urea dust. Fire Hazards Behavior in Fire: Melting and decomposing to generate ammonia. Not combustible. Gives off irritating or toxic fumes (or gases) in a fire. https://pubchem.ncbi.nlm.nih.gov/compound/urea#section=EPA-Safer-Chemical Handling and Storage Keep in a tightly closed container, stored in a cool, dry, ventilated area. Protect against physical damage. Isolate from incompatible substances. Containers of this material may be hazardous when empty since they retain product residues (dust, solids); observe all warnings and precautions listed for the product.

Reference

https://en.wikipedia.org/wiki/Urea#Explosives https://www.lookchem.com/ProductChemicalPropertiesCB5853861_EN.htm https://chemistry.stackexchange.com/questions/54387/extracting-urea-from-urine/60338#60338 http://www.chm.bris.ac.uk/motm/urea/urea.html? https://thechemco.com/chemical/urea/ ? file:///C:/Users/zl/Desktop/kurzer1956.pdf https://www.britannica.com/science/urea? http://www.expertsmind.com/topic/biochemistry/urea-cycle-96120.aspx http://sesl.com.au/blog/what-is-urea/? http://www.essentialchemicalindustry.org/chemicals/urea.html? http://www.atmos.umd.edu/~russ/MSDS/urea.htm

Description

Urea is a stable highly water-soluble compound of high nitrogen content (47%), with good storage properties that make it the most commonly used nitrogen fertilizer. The synthesis process has remained essentially unchanged since it was first developed by the BASF Corporation in 1922. In this process, liquid ammonia is reacted with carbon dioxide to produce ammonium carbamate, which is then dehydrated to form urea. The reactions are: 2NH3 + CO2 ===? NH2·CO2·NH4 NH2·CO2·NH4 ===? (NH2)2CO + H2O

Definition

Different sources of media describe the Definition of 57-13-6 differently. You can refer to the following data:
1. ChEBI: A carbonyl group with two C-bound amine groups.
2. A white crystalline compound made from ammonia and carbon dioxide. It is used in the manufacture of urea–formaldehyde (methanal) resins. Urea is the end product of metabolism in many animals and is present in urine.

Production Methods

Urea is an important industrial compound. The synthesis of urea was discovered in 1870.Commercial production of urea involves the reaction of carbon dioxide and ammonia at highpressure and temperature to produce ammonium carbamate. Ammonium carbamate is thendehydrated to produce urea (Figure 96.1). The reaction uses a molar ratio of ammonia tocarbon dioxide that is approximately 3:1 and is carried out at pressures of approximately 150atmospheres and temperatures of approximately 180°C.

Indications

Urea-containing preparations have a softening and moisturizing effect on the stratum corneum and, at times, may provide good therapy for dry skin and the pruritus associated with it. They appear to have an antipruritic effect apart from their hydrating qualities. Urea compounds disrupt the normal hydrogen bonds of epidermal proteins; therefore, their effect in dry hyperkeratotic diseases such as ichthyosis vulgaris and psoriasis is not only to make the skin more pliable but also to help remove adherent scales. Lactic acid also has a softening and moisturizing effect on the stratum corneum.Urea 40% ointment may be useful in removing hypertrophic or dystrophic psoriatic nails. Subsequent topical therapy to the denuded nail bed and proximal nail fold may result in regrowth of ‘‘normal’’ nails in half of those treated.

Preparation

All current processes for the manufacture of urea are based on the reaction of ammonia and carbon dioxide to form ammonium carbamate which is simultaneously dehydrated to urea: The dehydration of ammonium carbamate is appreciable only at temperatures above the melting point (about 150°C) and this reaction can only proceed if the combined partial pressure of ammonia and carbon dioxide exceeds the dissociation pressure of the ammonium carbamate (about 10 MPa at 160°C and about 30 MPa at 200°C). Thus commercial processes are operated in the liquid phase at 160-220°C and 18-35 MPa (180-350 atmospheres). Generally, a stoichiometric excess of ammonia is employed, molar ratios of up to 6: 1 being used. The dehydration of ammonium carbamate to urea proceeds to about 50-65% in most processes. The reactor effluent therefore consists of urea, water, ammonium carbamate and the excess of ammonia. Various techniques are used for separating the components. In one process the effluent is let down in pressure and heated at about 155°C to decompose the carbamate into ammonia and carbon dioxide. The gases are removed and cooled. All the carbon dioxide present reacts with the stoichiometric amount of ammonia to re-form carbamate, which is then dissolved in a small quantity of water and returned to the reactor. The remaining ammonia is liquefied and recycled to the reactor. Fresh make-up ammonia and carbon dioxide are also introduced into the reactor. Removal of ammonium carbamate and ammonia from the reactor effluent leaves an aqueous solution of urea. The solution is partially evaporated and then urea is isolated by recrystallization. Ammonium carbamate is very corrosive and at one time it was necessary to use silver-lined equipment but now satisfactory alloy steel plant is available.

Brand name

Ureaphil (Hospira).

Biological Functions

The use of urea (Ureaphil, Urevert) has declined in recent years owing both to its disagreeable taste and to the increasing use of mannitol for the same purposes. When used to reduce cerebrospinal fluid pressure, urea is generally given by intravenous drip. Because of its potential to expand the extracellular fluid volume, urea is contraindicated in patients with severe impairment of renal, hepatic, or cardiac function or active intracranial bleeding.

General Description

Solid odorless white crystals or pellets. Density 1.335 g /cc. Noncombustible.

Air & Water Reactions

Water soluble.

Reactivity Profile

Urea is a weak base. Reacts with hypochlorites to form nitrogen trichloride which explodes spontaneously in air [J. Am. Chem. Soc. 63:3530-32]. Same is true for phosphorus pentachloride. Urea reacts with azo and diazo compounds to generate toxic gases. Reacts with strong reducing agents to form flammable gases (hydrogen). The heating of improper stoichiometric amounts of Urea and sodium nitrite lead to an explosion. Heated mixtures of oxalic acid and Urea yielded rapid evolution of gases, carbon dioxide, carbon monoxide and ammonia (if hot, can be explosive). Titanium tetrachloride and Urea slowly formed a complex during 6 weeks at 80°C., decomposed violently at 90°C., [Chem. Abs., 1966, 64, 9219b]. Urea ignites spontaneously on stirring with nitrosyl perchlorate, (due to the formation of the diazonium perchlorate). Oxalic acid and Urea react at high temperatures to form toxic and flammable ammonia and carbon monoxide gasses, and inert CO2 gas [Von Bentzinger, R. et al., Praxis Naturwiss. Chem., 1987, 36(8), 41-42].

Health Hazard

May irritate eyes.

Fire Hazard

Behavior in Fire: Melts and decomposes, generating ammonia.

Agricultural Uses

Different sources of media describe the Agricultural Uses of 57-13-6 differently. You can refer to the following data:
1. Fertilizer, Fungicide: Used in fertilizers and animal feeds, as a fungicide, in the manufacture of resins and plastics, as a stabilizer in explosives and in medicines, and others. Urea is used to protect against frost and is used in some pesticides as an inert ingredient as a stabilizer, as an inhibitor and as an intensifier for herbicides. Registered for use in EU countries . Registered for use in the U.S.
2. Urea, CO(NH2)2, also referred to as carbamide, is a white, crystalline, organic, water-soluble fertilizer. It contains around 46 % nitrogen, the highest N percentage any solid fertilizer can have. Apart from its major use as a fertilizer, urea is also employed in the manufacture of paints, glues, plastics, paper, textiles, feed and weed control chemicals as well as a source of non-protein nitrogen. Urea is an acceptable fertilizer for rice and preferable to nitrates for flooded rice because of the reduction of nitrates to N,O and/or nitrogen (in anaerobic conditions) which is lost to the atmosphere. Also, rice can utilize the ammonium form of nitrogen efficiently. Hydrolysis and nitrification (in aerobic conditions) are rapid in tropical, sub-tropical and warm climates. Urea can thus be used efficiently but its use requires a better understanding than that required for other inorganic salts. It is applied to flooded soil three times: at the time of planting, tillering and panicle development. Similar to other nitrogenous fertilizers, urea promotes the growth of both weeds and crops. Urea solution after evaporation in vacuum evaporators, can be finally spraydried into pellets or prills. When protected from moisture (to which it is susceptible), urea is non-caking, freeflowing and suitable for storage and handling. However, the benefits of urea outweigh its disadvantages. Insofar as the weed growth is concerned, effective methods should be devised to minimize it to a manageable level. Urea is converted rapidly to ammonia by hydrolysis in the soil via the ammonium carbonate formation route, the latter being unstable (decomposing to ammonia and carbon dioxide). Urea is not as quick acting as ammonium nitrate because the nitrifying bacteria require a few days of warm and moist soil conditions to convert ammonia to the nitrate form. The formation of ammonium ion is slightly acidic in its ultimate reaction with the soil. Urea is decomposed by the enzyme urease and a part of urea is lost as gaseous nitrogen. The time between urea application and the first availability of water to the soil is important, as also the temperature, because the enzyme is less reactive in cold than at high temperature (25 to 30°C). Prevention and retardation of the hydrolytic action of urease is important following the addition of urea to soil. This may help to avoid difficulties associated with ammonia formation and alkalization. Many substances are urease inhibitors, but very few meet the rather specific requirements of being (a) effective at low concentrations, (b) relatively non-toxic to higher forms of life, (c) inexpensive, and (d) compatible with urea. Urea can be sprayed on leaves and can also be mixed with insecticides or herbicides for soil application. A urea-ammonium nitrate mixture with herbicide is also used for weed control. Urea, although an excellent fertilizer, suffers from the following drawbacks: (i) When applied to a bare soil surface, urea hydrolyzes rapidly and loses a significant quantity of ammonia by volatilization. Such losses vary from soil to soil and are greater for urea in a pellet form rather than in a solution form. Burning residues on the field is suggested as a practical means to control the ammonia loss because the burning reduces the concentration of the enzyme urease in plants. (ii) Rapid hydrolysis of urea in soils can cause injury to the seedlings by ammonia, if large quantities of the fertilizer are placed too close to the seeds. (iii) The fertilizer grade urea may contain toxic biuret which is formed during urea manufacture by an excessive temperature rise. A large concentration of biuret in urea ( > 2 %) causes injury to plants. Feed-grade urea is sometimes referred to by the number 262 which is the product of its nitrogen content (42%) multiplied by 6.25, the latter being the factor used by chemists to convert nitrogen to its protein equivalent. Urea is sometimes phytotoxic when placed close to seeds or seedlings. The phytotoxicity is caused by high local concentrations of ammonia during the hydrolysis stage or by accumulation of nitrite during the nitrification step. Another possible cause is the presence of biuret impurity in urea. The whole series of urea-formaldehyde compounds, ranging from soluble to completely water-insoluble, are produced by reacting urea with formaldehyde in different ratios. The fertilizer grade contains a minimum of 35% nitrogen, largely water-insoluble but in a gradually available form. The suitability of these compounds as fertilizers also depends on the quantity and quality of cold-water-insoluble nitrogen. The solubility reflects the rate at which the nitrogen becomes available. Formaldehyde-treated urea seems to be more waterproof and less subject to dissolution by light showers or heavy dew. In addition to the marked improvements in the size, strength and density of granular urea, urea has a number of good characteristics compared to ammonium nitrate. These include its (a) lesser tendency to stick and cake than ammonium nitrate, (b) insensitivity to fire and explosion, and (c) resistance to corrosion during handling and A popular urea-formaldehyde product in the USA contains 38% nitrogen (of which 28 % is water-insoluble) and has an activity index of 50. Urea-formaldehyde products are used to fertilize sod and certain speciality crops. As a result of the slow nitrification pattern, ureaformaldehyde prevents excessive leaching of nitrates. The use of urea-formaldehyde is not popular because it is costlier than the other nitrogenous fertilizers. The condensation product of urea and acetaldehyde is commercially known as urea-z. It is a slow-release nitrogen fertilizer containing around 31 % nitrogen. Urea crotonaldehyde, a derivative of urea (also known as crotonylidene diurea), is also a slow-release nitrogen fertilizer. Urea-sulphur is a relatively new compound containing 40% nitrogen and 10% sulphur. The prilled material has excellent physical properties. Its urea part dissolves after being applied to the soil, leaving elemental sulphur that is converted into sulphate by the oxidizing bacteria. Adding urea slurry to diammonium phosphate slurry (before or during granulation) makes urea-phosphate which has a higher nitrogen-to-phosphorus ratio than the ammonium phosphate does; the product contains 29% nitrogenand 12.7% phosphorus (29.0% P2O5). A new liquid fertilizer material [CO(NH2)2?H3PO4] is made by the reaction of urea, phosphoric acid and water. Depending on the ratio of the reactants, the nitrogen content varies from 10% to 28% and the phosphorus content from 9 to 18%.

Trade name

PRESPERSION, 75 UREA?; SUPERCEL 3000?; UREAPHIL?; UREOPHIL?; UREVERT?; VARIOFORM II?

Biochem/physiol Actions

Urea solution is primarily used for protein denaturation. It also increases solubility of hydrocarbons and reduce micelle formation. Urea solution at high concentration leads to the destabilization of amyloid β16?22 oligomers.

Safety Profile

Moderately toxic by intravenous and subcutaneous routes. Human reproductive effects by intraplacental route: ferthty effects. Experimental reproductive effects. Human mutation data reported. A human skin irritant. Questionable carcinogen with experimental carcinogenic and neoplastigenic data. Reacts with sodium hypochlorite or calcium hypochlorite to form the explosive nitrogen trichloride. Incompatible with NaNO2, P2Cl5, nitrosyl perchlorate. Preparation of the 15N-labeled urea is hazardous. When heated to decomposition it emits toxic fumes of NOx.

Potential Exposure

Urea is used in ceramics, cosmetics, paper processing; resins, adhesives, in animal feeds; in the manufacture of isocyanurates; resins, and plastics; as a stabilizer in explosives; in medicines; anticholelithogenic, and others.

Environmental Fate

Terrestrial Fate Urea is expected to have very high mobility in soil. Urea is not expected to volatilize from dry soil surfaces based on its vapor pressure. Various field and laboratory studies have demonstrated that urea degrades rapidly in most soils. Urea is rapidly hydrolyzed to ammonium ions through soil urease activity, which produces volatile gases, that is, ammonia and carbon dioxide. However, the rate of hydrolysis can be much slower, depending on the soil type, moisture content, and urea formulation. Aquatic Fate Urea is not expected to adsorb to suspended solids and sediments. Volatilization from water surfaces is not expected. Urea is rapidly hydrolyzed to ammonia and carbon dioxide in environmental systems by the extracellular enzyme urease, which originates from microorganisms and plant roots. Atmospheric Fate According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere, urea, which has a vapor pressure of 1.2×10-5mm Hg at 251°C, will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase urea is degraded in the atmosphere by reaction with photochemically produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 9.6 days.

Metabolism

The high analysis and good handling properties of urea have made it the leading nitrogen fertilizer, both as a source of nitrogen alone or when compounded with other materials in mixed fertilizers. Although an excellent source of nitrogen, urea can present problems unless properly managed; due to its rapid hydrolysis to ammonia, significant volatilization loss of this may occur if prilled or granular urea is applied to and left on the soil surface without timely incorporation. Mixtures of urea and ammonium nitrate for use in mixed fertilizers are also more highly hygroscopic than ammonium nitrate itself.

Purification Methods

Crystallise urea twice from conductivity water using centrifugal drainage and keeping the temperature below 60o. The crystals are dried under vacuum at 55o for 6hours. Levy and Margouls [J Am Chem Soc 84 1345 1962] prepared a 9M solution in conductivity water (keeping the temperature below 25o) and, after filtering through a medium-porosity glass sinter, added an equal volume of absolute EtOH. The mixture was set aside at -27o for 2-3 days and filtered cold. The precipitate was washed with a small amount of EtOH and dried in air. Crystallisation from 70% EtOH between 40o and -9o has also been used. Ionic impurities such as ammonium isocyanate have been removed by treating the concentrated aqueous solution at 50o with Amberlite MB-1 cation-and anion-exchange resin, and allowing it to crystallise on evaporation. [Benesch et al. J Biol Chem 216 663 1955.] It can also be crystallised from MeOH or EtOH, and is dried under vacuum at room temperature. [Beilstein 3 H 42, 3 I 19, 3 II 35, 3 III 80.]

Toxicity evaluation

The primary mechanism of toxicity appears to be inhibition of the citric acid cycle. It leads to blockade of electron transport and a decrease in energy production and cellular respiration, which leads to convulsions.

Incompatibilities

Violent reaction with strong oxidizers, chlorine, permanganates, dichromates, nitrites, inorganic chlorides; chlorites, and perchlorates. Contact with hypochlorites can result in the formation of explosive compounds.

Waste Disposal

Controlled incineration in equipment containing a scrubber or thermal unit to reduce nitrogen oxide emissions.

InChI:InChI=1/CH4N2O/c2-1(3)4/h(H4,2,3,4)

Synthetic route

ammonium cyanate (22981-32-4) → urea (57-13-6)

Conditions	Yield
In ethanol at 32°C;	100%
In ethanol at 32°C;	100%
In water Kinetics; izomerization; equil. react.;

S,S-dimethyl dithiocarbonate (868-84-8) → urea (57-13-6)

Conditions	Yield
With ammonia; water at 60℃; for 2h;	100%

carbon monoxide (201230-82-2) + ammonia (7664-41-7) + sulfur (7704-34-9) → hydrogen sulfide (7783-06-4) + urea (57-13-6)

Conditions	Yield
In methanol; water molar ratio of CO:S = 1.36; 35 min; at 110°C; 60% excess of NH3; 75% CH3OH;	A n/a B 96.2%
In methanol; water molar ratio of NH3:S:CO = 1.4 : 1 : 1.36; 35 min; at 110°C; 54% CH3OH;	A n/a B 96.2%
In methanol; water molar ratio of NH3:S:CO = 1.4 : 1 : 1.36; 35 min; at 110°C; 54% CH3OH;	A n/a B 96.3%

thiourea (17356-08-0) → urea (57-13-6)

Conditions	Yield
With bismuth(III) nitrate In acetonitrile for 0.25h; Heating;	96%
With Oxone for 0.0833333h;	96%
With 3-carboxypyridinium chlorochromate In acetonitrile for 0.0333333h; Product distribution; Further Variations:; Reagents; Temperatures; without microwave irradiation; solvent-free; microwave irradiation;	95%

Difluoroacetic acid (381-73-7) + 3,3-diphenylpropan-1-ol (20017-67-8) → difluoroacetic acid, O-(3,3-diphenyl-propyl) ester + urea (57-13-6)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In diethyl ether at 0 - 20℃;	A 96% B n/a

nitrourea (556-89-8) + ammonia (7664-41-7) → urea (57-13-6) + nitramine (7782-94-7)

Conditions	Yield
In ammonia at -33°C;	A 91% B n/a

tetrafluoroboric acid diethyl ether (67969-82-8) + F6P(1-)*C25H43Fe2N2OS2(1+) + acetonitrile (75-05-8) → F6P(1-)*C26H44Fe2N4S2(2+)*BF4(1-) + urea (57-13-6)

Conditions	Yield
In acetone at 20℃; for 2h; Inert atmosphere; Schlenk technique;	A 90% B 90%

sodium methylate (124-41-4) + 4-ureidocarbonylpyrazole (80981-23-3) → methyl pyrazole-4-carboxylate (51105-90-9) + urea (57-13-6)

Conditions	Yield
In methanol for 2h; Heating;	A 89% B n/a

carbon oxide sulfide (463-58-1) + ammonia (7664-41-7) → hydrogen sulfide (7783-06-4) + urea (57-13-6)

Conditions	Yield
1.5-fold molar excess of NH3; at 105°C;	A n/a B 88%
In ethanol at a temp. near the m.p. of urea; using abs. ethanol;	A n/a B 76%
In ammonia at a temp. near the m.p. of urea;	A n/a B 64%

iron pentacarbonyl (13463-40-6) + ammonia (7664-41-7) → 2NH4(1+)*{Fe(CO)4}(2-)=(NH4)2{Fe(CO)4} + urea (57-13-6)

Conditions	Yield
With ammonium chloride In ammonia at exclusion of light, air and moisture; 20°C; 5 d;	A n/a B 85%
In ammonia at exclusion of light, air and moisture; 20°C; 5 d;	A n/a B 77%
In ammonia at exclusion of light, air and moisture; 20°C; 1 d;	A n/a B 31%
In ammonia at exclusion of light, air and moisture; 20°C; 14 d;	A n/a B >99

CYANAMID (420-04-2) → urea (57-13-6)

Conditions	Yield
With [OsCl2(η6-p-cymene)(PMe2OH)]; water at 40℃; for 0.25h; Reagent/catalyst; Inert atmosphere; Sealed tube;	80%
With sulfuric acid

ammonium oxythiocarbamate (16687-42-6) → ammonium cyanate (22981-32-4) + sulfur (7704-34-9) + urea (57-13-6)

Conditions	Yield
In ethanol storing in air; elimination of the ppt.; crystn. S by HgO at low temp.;	A n/a B n/a C 80%
In ethanol storing in air; elimination of the ppt.; crystn. S by HgO at low temp.;	A n/a B n/a C 80%
In ethanol storing in air; elimination of the ppt.; crystn. S by HgO at low temp.;	A n/a B n/a C 80%

carbon dioxide (124-38-9) + ammonia (7664-41-7) → urea (57-13-6)

Conditions	Yield
at molar ratio of NH3:CO2 = 8;	77%
High Pressure; at 175 until 180°C; at a pressure of 175 at; molar ratio of NH3:CO2 = 6; liquid phase;	76%
at molar ratio of NH3:CO2 = 6;	72%

propan-1-ol (71-23-8) + carbon monoxide (201230-82-2) + 1-amino-3-(dimethylamino)propane (109-55-7) → propamocarb (24579-73-5) + urea (57-13-6)

Conditions	Yield
With oxygen; N,N-dimethyl-formamide; sodium iodide; palladium dichloride at 125℃; under 30003 Torr; for 2h; Pressure; Reagent/catalyst; Autoclave; Inert atmosphere;	A 75.6% B 5.7%

nitro-carboxamide → 5-Amino-4-chloro-2-[8'-benzyl-8'-azabicyclo-[3.2.1]octane-3'β-carboxamido]-anisole + urea (57-13-6)

Conditions	Yield
aluminum nickel In ethanol	A 73% B n/a

uric Acid (69-93-2) → pyrimidine-2,4,5,6(1H,3H)-tetraone (61066-33-9, 61066-34-0, 61066-35-1, 61127-23-9) + urea (57-13-6)

Conditions	Yield
With rose bengal; sodium hydroxide In glycerol for 36h; Irradiation;	A 72.18% B n/a

ethyl 4-(4-chlorophenyl)-1,2,3,4-tetrahydro-6-methyl-2-thioxopyrimidine-5-carboxylate (154866-92-9) → (4-chlorobenzylidene)hydrazine (52372-80-2) + thiourea (17356-08-0) + urea (57-13-6) + 5-hydroxy-3-methylpyrazole (132712-71-1, 4344-87-0, 145091-87-8)

Conditions	Yield
With hydrazine hydrate In neat (no solvent) for 6h; Reflux;	A 70% B n/a C n/a D 55%

5-carboethoxy-6-methyl-4-(4-methylphenyl)-1H-pyrimidin-2-thione (185023-34-1) → 4-methylbenzaldehyde hydrazone (52693-87-5) + thiourea (17356-08-0) + urea (57-13-6) + 5-hydroxy-3-methylpyrazole (132712-71-1, 4344-87-0, 145091-87-8)

Conditions	Yield
With hydrazine hydrate In neat (no solvent) for 6h; Reflux;	A 69% B n/a C n/a D 55%

ammonia (7664-41-7) + polycarbonate → BPA (80-05-7) + urea (57-13-6)

Conditions	Yield
In ethanol; water at 80℃; for 12h; Green chemistry;	A n/a B 68%

5-ethoxycarbonyl-4-phenyl-6-methyl-3,4-dihydropyrimidine-2(1H)-thione (123043-88-9, 33458-26-3) → benzaldehyde, hydrazone (5281-18-5) + thiourea (17356-08-0) + urea (57-13-6) + 5-hydroxy-3-methylpyrazole (132712-71-1, 4344-87-0, 145091-87-8)

Conditions	Yield
With hydrazine hydrate In neat (no solvent) for 6h; Reflux;	A 67% B n/a C n/a D 55%

propan-1-ol (71-23-8) + carbon monoxide (201230-82-2) + N-butylamine (109-73-9) → urea (57-13-6) + n-propyl N-n-butyl carbamate (100823-18-5)

Conditions	Yield
With oxygen; triethylamine; sodium iodide; palladium dichloride at 165℃; Reagent/catalyst; Autoclave; Inert atmosphere;	A 66% B 8%

5-(ethoxycarbonyl)-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-thione (113697-57-7) → p-anisaldehyde hydrazone (5953-85-5) + thiourea (17356-08-0) + urea (57-13-6) + 5-hydroxy-3-methylpyrazole (132712-71-1, 4344-87-0, 145091-87-8)

Conditions	Yield
With hydrazine hydrate In neat (no solvent) for 6h; Reflux;	A 66% B n/a C n/a D 55%

4-(4-chlorophenyl)-5-(ethoxycarbonyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (5948-71-0) → (4-chlorobenzylidene)hydrazine (52372-80-2) + thiourea (17356-08-0) + urea (57-13-6) + 5-hydroxy-3-methylpyrazole (132712-71-1, 4344-87-0, 145091-87-8)

Conditions	Yield
With hydrazine hydrate In neat (no solvent) for 6h; Reflux;	A 62% B n/a C n/a D 55%

ethyl 6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one-5-carboxylate (123237-03-6, 5395-36-8) → benzaldehyde, hydrazone (5281-18-5) + thiourea (17356-08-0) + urea (57-13-6) + 5-hydroxy-3-methylpyrazole (132712-71-1, 4344-87-0, 145091-87-8)

Conditions	Yield
With hydrazine hydrate In neat (no solvent) for 6h; Reflux;	A 62% B n/a C n/a D 55%

carbon dioxide (124-38-9) + ammonia (7664-41-7) + water (7732-18-5) → urea (57-13-6)

Conditions	Yield
at 190℃; under 112511 Torr;	61%

ethyl 4-(4-methoxyphenyl)-6-methyl-1,2,3,4-tetrahydropyrimidin-2-one-5-carboxylate (161374-07-8) → p-anisaldehyde hydrazone (5953-85-5) + thiourea (17356-08-0) + urea (57-13-6) + 5-hydroxy-3-methylpyrazole (132712-71-1, 4344-87-0, 145091-87-8)

Conditions	Yield
With hydrazine hydrate In neat (no solvent) for 6h; Reflux;	A 60% B n/a C n/a D 55%

ethyl 6-methyl-2-oxo-4-p-tolyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (299949-24-9) → 4-methylbenzaldehyde hydrazone (52693-87-5) + thiourea (17356-08-0) + urea (57-13-6) + 5-hydroxy-3-methylpyrazole (132712-71-1, 4344-87-0, 145091-87-8)

Conditions	Yield
With hydrazine hydrate In neat (no solvent) for 6h; Reflux;	A 58% B n/a C n/a D 55%

ammonium carbamate → water (7732-18-5) + urea (57-13-6)

Conditions	Yield
Kinetics; at 200°C;	A n/a B 55%
Kinetics; at 200°C;	A n/a B 55%
Kinetics; at 140°C;	A n/a B 43%

uric Acid (69-93-2) → 5,6-dihydroxypyrimidine-2,4(1H,3H)-dione (102636-37-3) + urea (57-13-6)

Conditions	Yield
With rose bengal In acetic acid; glycerol for 38h; Irradiation;	A 45.11% B n/a

maleic anhydride (108-31-6) + urea (57-13-6) → maleuric acid (105-61-3)

Conditions	Yield
With acetic acid at 50℃; for 12h;	100%
With acetic acid
at 80℃;
at 100 - 105℃;
With acetic acid

ethyl acetoacetate (141-97-9) + 4-nitrobenzaldehdye (555-16-8) + urea (57-13-6) → ethyl 6-methyl-4-(4-nitrophenyl)-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate (123371-45-9)

Conditions	Yield
With 1-methylimidazole based ionic liquid terminated dendritic moiety prepared from 2,4,6-trichloro-1,3,5-triazine and 1,3-diaminopropane immobilized on 3-aminopropyltriethoxysilane functionalized bentonite In ethanol; water at 50℃; for 3h; Biginelli Pyrimidone Synthesis; Green chemistry;	100%
With guanidine In neat (no solvent) at 80℃; for 2h; Biginelli Pyrimidone Synthesis;	99%
With 1,4-diazaniumbicyclo[2.2.2]octane diacetate In neat (no solvent) at 80℃; for 0.0833333h; Biginelli Pyrimidone Synthesis; Green chemistry;	99%

ethyl acetoacetate (141-97-9) + benzaldehyde (100-52-7) + urea (57-13-6) → ethyl 6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one-5-carboxylate (123237-03-6, 5395-36-8)

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate) In ethanol at 100℃; for 1h; Biginelli reaction; Microwave irradiation; Inert atmosphere;	100%
With Cl7Fe2(1-)*C6H9N2O2(1+); C8H15N2(1+)*C4H12B(1-) at 80℃; for 2h; Reagent/catalyst; Biginelli Pyrimidone Synthesis;	99%
With guanidine In neat (no solvent) at 80℃; for 2h; Biginelli Pyrimidone Synthesis;	99%

dimethylglyoxal (431-03-8) + urea (57-13-6) → tetrahydro-3a,6a-dimethylimidazo<4,5-d>imidazole-2,5-(1H,3H)-dione (28115-25-5)

Conditions	Yield
With H3PW12O40 In methanol at 20℃; for 5.5h;	100%
With 1-hydroxyethylene-(1,1-diphosphonic acid) In water at 80℃; for 1h; Green chemistry;	95%
With hydrogenchloride In water at 20℃; for 12h;	76%

3-amino-4-hydroxytoluene (95-84-1) + urea (57-13-6) → 5-methylbenzo[d]oxazol-2(3H)-one (22876-15-9)

Conditions	Yield
In N,N-dimethyl-formamide at 145 - 150℃; for 3.5h;	100%
at 144.85 - 149.85℃; for 4h;	59.69%
In N,N-dimethyl-formamide for 5h; Carbonylation; Heating;	55%

urea (57-13-6) + hydroxy-phenyl-acetic acid ethyl ester (774-40-3, 4358-88-7) → 5-phenyloxazolidine-2,4-dione (5841-63-4)

Conditions	Yield
With sodium ethanolate; sodium hydride In ethanol at 0℃; for 2.5h; Reflux;	100%
With sodium ethanolate In ethanol at 0℃; for 4h; Reflux;	17.04%
With sodium methylate Hydrolysieren des Reaktionsprodukts;

urea (57-13-6) + 2-Amino-4-chlorobenzoic acid (89-77-0) → 7-chloroquinazoline-2,4-dione (13165-35-0)

Conditions	Yield
at 200℃; for 1h;	100%
at 200℃; for 2h;	85%
With sodium hydroxide In water for 120h; Heating;	33%

urea (57-13-6) → urea, monosodium salt (29878-39-5)

Conditions	Yield
With sodium hydride; toluene at 25 - 90℃; for 1.5h; Reagent/catalyst;	100%
With sodium methylate In methanol; 5,5-dimethyl-1,3-cyclohexadiene at 120℃;	93%
With sodium methylate In methanol; 5,5-dimethyl-1,3-cyclohexadiene at 120℃;	93%
With ammonia; sodium

ethyl acetoacetate (141-97-9) + 4-methoxy-benzaldehyde (123-11-5) + urea (57-13-6) → ethyl 4-(4-methoxyphenyl)-6-methyl-1,2,3,4-tetrahydropyrimidin-2-one-5-carboxylate (161374-07-8)

Conditions	Yield
With piperidine In ethanol for 4h; Heating;	100%
With copper(II) bis(trifluoromethanesulfonate) In ethanol at 100℃; for 1h; Biginelli reaction; Microwave irradiation; Inert atmosphere;	100%
With CuCl2*2H2O for 0.025h; Biginelli condensation; microwave irradiation;	99%

1-(2-hydroxyphenyl)-3-(4-methoxyphenyl)-2-propen-1-one (3327-24-0) + urea (57-13-6) → 2-oxo-4-(o-hydroxyphenyl)-6-(p-methoxyphenyl)-1,3,6-trihydro-pyrimidine

Conditions	Yield
With sulfuric acid In ethanol for 8h; Heating;	100%

ethyl acetoacetate (141-97-9) + 4-chlorobenzaldehyde (104-88-1) + urea (57-13-6) → 4-(4-chlorophenyl)-5-(ethoxycarbonyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (5948-71-0)

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate) In ethanol at 100℃; for 1h; Biginelli reaction; Microwave irradiation; Inert atmosphere;	100%
With [1-(3-sulfonic acid)]propyl-3-methylimidazolium hydrogen sulfate In ethanol at 80℃; for 3h; Time; Biginelli Pyrimidone Synthesis;	99%
Stage #1: ethyl acetoacetate; 4-chlorobenzaldehyde With secondary amine linked triazine and pyrene containing microporous organic polymer at 40 - 80℃; for 0.5h; Stage #2: urea for 2h; Biginelli Pyrimidone Synthesis; Reflux;	99%

4-methoxy-benzaldehyde (123-11-5) + acetoacetic acid methyl ester (105-45-3) + urea (57-13-6) → 5-methoxycarbonyl-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (205999-87-7)

Conditions	Yield
With sulfuric acid; copper(l) chloride In methanol Biginelli Pyrimidone Synthesis; Reflux; Inert atmosphere;	100%
With ytterbium(III) triflate at 100℃; for 0.333333h; Biginelli reaction;	99%
With calcium chloride In ethanol for 2h; Biginelli reaction; Heating;	98%

4-methoxy-benzaldehyde (123-11-5) + urea (57-13-6) + ethyl propanoylacetate (4949-44-4) → ethyl 6-ethyl-4-(4-methoxyphenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate) In ethanol at 100℃; for 1h; Biginelli reaction; Microwave irradiation; Inert atmosphere;	100%
With Aliquat 336; sodium hydroxide In water at 100℃; for 0.75h; Reagent/catalyst; Solvent; Temperature; Time;	91%
With zinc(II) oxide In water for 0.416667h; Biginelli Pyrimidone Synthesis;	86%

ethyl acetoacetate (141-97-9) + urea (57-13-6) + ortho-bromobenzaldehyde (6630-33-7) → ethyl 4-(2-bromophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate) In ethanol at 100℃; for 1h; Biginelli reaction; Microwave irradiation; Inert atmosphere;	100%
With ytterbium(III) triflate at 100℃; for 0.666667h; Biginelli reaction;	97%
With 2,2,2-trifluoroethanol at 80℃; Biginelli pyrimidine synthesis;	94%

4-methyl-benzaldehyde (104-87-0) + ethyl acetoacetate (141-97-9) + urea (57-13-6) → ethyl 6-methyl-2-oxo-4-p-tolyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (299949-24-9)

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate) In ethanol at 100℃; for 1h; Biginelli reaction; Microwave irradiation; Inert atmosphere;	100%
polystyrene-methylimidazolium(1+)*PF6(1-) In acetic acid at 100℃; for 2h;	99%
With indium(III) bromide In ethanol for 7h; Biginelli condensation; Heating;	98%

2-methyl-benzyl alcohol (89-95-2) + ethyl acetoacetate (141-97-9) + urea (57-13-6) → ethyl 4-(2-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (5948-68-5)

Conditions	Yield
With piperidine In ethanol for 4h; Heating;	100%
With 3-ethoxycarbonylmethyl-1-methylimidazolium hydrogen sulfate at 80℃; for 0.25h; Biginelli reaction;	92%
With In(OSO2CF3)3 for 0.183333h; Biginelli reaction; microwave irradiation;	91%

ethyl acetoacetate (141-97-9) + 1-naphthaldehyde (66-77-3) + urea (57-13-6) → 6-methyl-4-naphthalen-1-yl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester (219814-93-4, 1032574-17-6)

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate) In ethanol at 100℃; for 1h; Biginelli reaction; Microwave irradiation; Inert atmosphere;	100%
With copper doped mesoporous silica MCM-41 supported dual acidic ionic liquid-HSO4 In ethanol at 80℃; for 1h; Biginelli Pyrimidone Synthesis;	97%
Stage #1: 1-naphthaldehyde; urea With hydrogenchloride In tetrahydrofuran; water at 67℃; for 1h; Biginelli Pyrimidone Synthesis; Green chemistry; Stage #2: ethyl acetoacetate With N,N′-(cyclohexane-1,2-diyl)bis(3,6-dichloropicolinamide) In tetrahydrofuran; water at 67℃; for 5h; Biginelli Pyrimidone Synthesis; Green chemistry;	95%

indan-1,2,3-trione hydrate (485-47-2) + urea (57-13-6) → 3a,8a-dihydroxy-1,3,3a,8a-tetrahydroindeno[1,2-d]imidazole-2,8-dione (22431-00-1)

Conditions	Yield
at 80℃; for 1h;	100%
In water at 20℃; for 0.833333h; Green chemistry;	98%
In water at 50 - 60℃;	93%

urea (57-13-6) → nitrourea (556-89-8)

Conditions	Yield
With nitric acid for 2h;	100%
With nitric acid at 20℃; for 2h; Neat (no solvent);	100%
With nitric acid at 20℃; for 2h;	100%

3-(4-nitrophenyl)-2-oxopropanoic acid (38335-24-9) + benzaldehyde (100-52-7) + urea (57-13-6) → 5-(4-nitro-phenyl)-2-oxo-6-phenyl-1,2,3,6-tetrahydro-pyrimidine-4-carboxylic acid

Conditions	Yield
With methanesulfonic acid In ethanol for 24h; Biginelli reaction; Heating;	100%

urea (57-13-6) + Triphenylphosphine oxide (791-28-6) → 2,2,2-triphenyl-1H-1,3,2,λ5-diazaphosphotidin-4-one

Conditions	Yield
at 95 - 100℃; for 4h;	100%

methyl 3-amino-4-formylbenzoate (212322-17-3) + urea (57-13-6) → methyl 2-hydroxy-quinazoline-7-carboxylate (953039-78-6)

Conditions	Yield
at 145℃; for 16h;	100%

1-(2-amino-4-methoxyphenyl)ethanone (42465-53-2) + urea (57-13-6) → 7-methoxy-4-methyl-quinazolin-2-ol (37528-39-5)

Conditions	Yield
With acetic acid at 100℃; for 16h;	100%

1-(2-amino-3-methoxyphenyl)ethanone (42465-54-3) + urea (57-13-6) → 8-methoxy-4-methyl-quinazolin-2-ol (953039-91-3)

Conditions	Yield
With acetic acid at 100℃; for 16h;	100%

ethyl acetoacetate (141-97-9) + urea (57-13-6) + 4-(Methylthio)benzaldehyde (3446-89-7) → ethyl 6-methyl-4-[4-(methylsulfanyl)phenyl]-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate (423737-44-4)

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate) In ethanol at 100℃; for 1h; Biginelli reaction; Microwave irradiation; Inert atmosphere;	100%
Wells-Dawson heteropolyacid catalyst at 80℃; for 1.5h; Biginelli reaction;	92%
With 25,26,27,28-terahydroxycalix[4]arene-5,11,7,23-tetrasulfonic acid In ethanol for 8h; Biginelli reaction; Reflux;	92%

C20H8N2O4 + urea (57-13-6) + zinc(II) chloride (7646-85-7) → C80H32N8O16Zn

Conditions	Yield
With ammonium molibdate; 1,8-diazabicyclo[5.4.0]undec-7-ene at 240℃; for 3h;	100%

(2R)-2-hydroxy-2-(3-methylphenyl)propanoic acid methyl ester (877681-24-8) + urea (57-13-6) → (5R)-5-methyl-5-(3-methylphenyl)oxazolidine-2,4-dione (875542-02-2)

Conditions	Yield
With sodium ethanolate In ethanol at 95℃;	100%
With sodium ethanolate In ethanol Heating / reflux;
With sodium ethanolate In ethanol at 95℃; Heating / reflux;

5-Amino-1-(2-phenylethyl)-1H-pyrazole-4-carboxylic acid (443107-13-9) + urea (57-13-6) → C13H12N4O2 (443107-17-3)

Conditions	Yield
at 180℃;	100%

choline chloride (67-48-1) + urea (57-13-6) → urea/choline chloride eutectic salt

Conditions	Yield
at 70 - 80℃; for 0.333333h;	100%
at 120℃; for 0.333333h; Neat (no solvent);
at 74℃;

Upstream product

• 97-59-6 Allantoin 
• 102-09-0 bis(phenyl) carbonate 
• 61066-33-9 pyrimidine-2,4,5,6(1H,3H)-tetraone 
• 10329-48-3 N-hydroxyoxamide 
• 64-17-5 ethanol 
• 22243-66-9 3-ureido-crotonic acid ethyl ester 
• 110-14-5 butanediamide 
• 638-32-4 succinamic acid 
• 463-00-3 4-guanidinobutyric acid 
• 101970-86-9 methyl 1,1,1-trichloromethyl carbonate 
• 585-05-7 oxaluric acid 
• 98019-46-6 carbonic acid ethyl ester-trichloromethyl ester 
• 58-08-2 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione 
• 64-10-8 phenyl carbamate 

Downstream Products

• 497-25-6 dimethylenecyclourethane 
• 142-27-8 carbamic acid-(2-amino-ethyl ester) 
• 2078-71-9 (2-hydroxyethyl)urea 
• 10581-05-2 piperazine-1,4-dicarboxylic acid diamide 
• 18592-13-7 6-chloromethyluracil 
• 5657-22-7 morpholinomethylurea 
• 626-48-2 6-Methyluracil 
• 6268-43-5 1,3-di-pyridin-2-yl-urea 
• 219539-12-5 1-(thiophen-2-ylmethyl)urea 
• 105-61-3 maleuric acid 
• 98-92-0 nicotinamide 
• 16328-62-4 1,3-dihydro-imidazo[4,5-b]pyridin-2-one 
• 97-59-6 Allantoin 
• 32451-61-9 [8]quinolyl-urea 

Relevant articles and documents

Real-Time in Vivo Detection of H2O2 Using Hyperpolarized 13C-Thiourea

Reactive oxygen species (ROS) are essential cellular metabolites widely implicated in many diseases including cancer, inflammation, and cardiovascular and neurodegenerative disorders. Yet, ROS signaling remains poorly understood, and their measurements are a challenge due to high reactivity and instability. Here, we report the development of 13C-thiourea as a probe to detect and measure H2O2 dynamics with high sensitivity and spatiotemporal resolution using hyperpolarized 13C magnetic resonance spectroscopic imaging. In particular, we show 13C-thiourea to be highly polarizable and to possess a long spin-lattice relaxation time (T1), which enables real-time monitoring of ROS-mediated transformation. We also demonstrate that 13C-thiourea reacts readily with H2O2 to give chemically distinguishable products in vitro and validate their detection in vivo in a mouse liver. This study suggests that 13C-thiourea is a promising agent for noninvasive detection of H2O2 in vivo. More broadly, our findings outline a viable clinical application for H2O2 detection in patients with a range of diseases.

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Evidence for an inhibitory LIM domain in a rat brain agmatinase-like protein

We recently cloned a rat brain agmatinase-like protein (ALP) whose amino acid sequence greatly differs from other agmatinases and exhibits a LIM-like domain close to its carboxyl terminus. The protein was immunohistochemically detected in the hypothalamic region and hippocampal astrocytes and neurons. We now show that truncated species, lacking the LIM-type domain, retains the dimeric structure of the wild-type protein but exhibits a 10-fold increased kcat, a 3-fold decreased Km value for agmatine and altered intrinsic tryptophan fluorescent properties. As expected for a LIM protein, zinc was detected only in the wild-type ALP (～2 Zn2+/monomer). Our proposal is that the LIM domain functions as an autoinhibitory entity and that inhibition is reversed by interaction of the domain with some yet undefined brain protein.

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Aminoguanidinium hydrolysis effected by a hydroxo-bridged Dicobalt(II) complex as a functional model for arginase and catalyzed by mononuclear Cobalt(II) complexes

The dinuclear complex [Co2(μ-OH)(μ-XDK)(bpy)2(EtOH)](NO3), where XDK is the dinucleating dicarboxylate ligand m-xylylenediamine bis(Kemp's triacid imide) and bpy = 2,2'-bipyridine, was prepared as a functional model for arginase. The substrate aminoguanidinium nitrate was hydrolyzed to urea in ethanol by the complex but not by free hydroxide ion under the same conditions. The amino group of the substrate binds to cobalt, as demonstrated by W-vis spectroscopic studies. The syntheses of related dinuclear cobalt(II) complexes [Co2(μ-XDK)(NO3)2(CH3OH)2(H2O)], [Co2(μ-Cl)(μ-XDK)(bpy)2(EtOH)2](NO3), and [Co2(μ-XDK)-(py)3(NO3)2] are described. Mononuclear complexes [Co(XDK)(bpy)(H2O)] and [Zn(XDK)(bpy)(H2O)] were also prepared and characterized. The former catalytically hydrolyzes aminoguanidinium nitrate to urea in basic 1:1 methanol/water solutions, whereas the latter does not promote this reaction. Hydrolysis of aminoguanidinium ion is effected by [Co(CH3COO)2] and [Cu(CH3COO)2] in the presence of bpy, but not by [Zn(CH3COO))2], [Ni(CH3COO)2], or [Mn(CH3COO)2] in the presence of bpy in 1:1 methanol/water solution. In all cases, coordination of the amino group of the substrate to the metal center under the reaction conditions may activate the leaving group and orient the guanidinium moiety close to the attacking nucleophile, metal-bound hydroxide ion, to promote the hydrolysis reaction.

Photocatalytic synthesis of urea from in situ generated ammonia and carbon dioxide

TiO2 and Fe-titanate (different wt%) supported on zeolite were prepared by sol-gel and solid-state dispersion methods. The photocatalysts prepared were characterized by X-ray diffraction, scanning electron microscopy and ultraviolet (UV)-visible diffuse reflectance spectroscopy techniques. Photocatalytic reduction of nitrate in water and isopropanol/oxalic acid as hole scavengers are investigated in a batch reactor under UV illumination. The yield of urea increased notably when the catalysts were supported on zeolite. The Fe-titanate supported catalyst promotes the charge separation that contributes to an increase in selective formation of urea. The product formation is because of the high adsorption of in situ generated CO2 and NH3 over shape-selective property of the zeolite in the composite photocatalyst. The maximum yield of urea is found to be 18 ppm while 1% isopropanol containing solution over 10 wt% Fe-titanate/HZSM-5 photocatalyst was used.

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Oxyhalogen-sulfur chemistry: Kinetics and mechanism of oxidation of formamidine disulfide by acidic bromate

The kinetics and mechanism of the oxidation of formamidine disulfide, FDS, a dimer and major metabolite of thiourea, by bromate have been studied in acidic media. In excess bromate conditions the reaction displays an induction period before formation of bromine. The stoichiometry of the reaction is: 7BrO3- + 3[(H2N(HN=)CS-]2 + 9H 2O → 6NH2CONH2 + 6SO4 2- + 7Br- + 12H- (A). In excess oxidant conditions, however, the bromide formed in reaction A reacts with bromate to give bromine and a final stoichiometry of: 14BrO3- + 5[(H2N(HN=)CS-]2 + 8H2O → 10NH 2CONH2 + 10SO42- + 7Br2 + 6H+ (B). The direct reaction of bromine and FDS was also studied and its stoichiometry is: 7Br2 + [(H2N(HN=)CS-] 2 + 10H2O → 2NH2CONH2 + 2SO42- + 14Br- + 18H+ (C). The overall rate of reaction A, as measured by the rate of consumption of FDS, is second order in acid concentrations, indicating the dominance of oxyhalogen kinetics which control the formation of the reactive species HBrO2 and HOBr. The reaction proceeds through an initial cleavage of the S-S bond to give the unstable sulfenic acids which are then rapidly oxidized through the sulfinic and sulfonic acids to give sulfate. The formation of bromine coincides with formation of sulfate because the cleavage of the C-S bond to give sulfate occurs at the sulfonic acid stage only. The mechanism derived is the same as that derived for the bromate-thiourea reaction, suggesting that FDS is an intermediate in the oxidation of thiourea to its oxo-acids as well as to sulfate.

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Oxyhalogen-Sulfur Chemistry: The Bromate-(Amininoimino)methanesulfinic Acid Reaction in Acidic Medium

The reaction between (amnoimino)methanesulfinic acid, HO2SC(NH)NH2(AIMSA), and bromate has been studied in acidic medium.In excess AIMSA the stoichiometry of the reaction is 2BrO3- + 3AIMSA + 3H2O -> 3SO42- + 3CO(NH2)2 + 2Br- + 6H+, and in excess bromate the stoichiometry is 4BrO3- + 5AIMSA + 3H2O -> 5SO42- + 5CO(NH2)2 + 2Br2 + 6H+.Br2 is produced only when BrO3- is in stoichiometric excess over AIMSA.It is produced from the reaction of the product, Br-, with excess BrO3- after all the AIMSA has been consumed.The reaction has an initial induction period followed by formation of bromine.Although AIMSA is oxidized to SO42-, no SO42- formation is observed until Br2 production commences.The reaction is autocatalyzed by bromide.The reactive oxidizing species in solution are HOBr and Br2.Bromide enhances their formation from bromate.A simple eight-reaction mechanism is used to describe the reaction.The reaction commences through a direct reaction between BrO3- and AIMSA: BrO3+ + HO2SC(NH)NH2 + H+ -> HBrO2 + HO3SC(NH)NH2 with k = 2.5E-2M-2s-1.The rate-determining step is the standard BrO3- - Br- reaction which forms the reactive species HOBr:BrO3- + Br- + 2H+ -> HBrO2 + HOBr.A computer simulation analysis of the proposed mechanism gave good fit to the data.

Spectroscopic study of photo and thermal destruction of riboflavin

Influence of temperature and light irradiation on the spectroscopic properties of aqueous solutions of riboflavin was studied using linear dichroism method, absorption and fluorescence spectroscopy. It was established that in a wide temperature range 290-423 K there is a decline of absorbance and fluorescence ability, which is explained by thermodestruction of riboflavin. It is shown that the proportion of molecules, which have undergone degradation, are in the range of 4-28%, and depends on the concentration and quantity of temperature effects. Introduction of hydrochloric and sulfuric acids, as well as different metal ions leads to an increase in the photostability of riboflavin solutions by 2-2.5 times. The observed phenomena are explained by the formation protonation form of riboflavin and a complex between the metal ions and oxygen atoms of the carbonyl group of riboflavin, respectively.

Formation of adenine from CH3COONH4/NH 4HCO3-the probable prebiotic route for adenine

Adenine was formed when an aqueous solution of CH3COONH 4/NH4HCO3 was subjected to mass spectrometer/refluxed for 72 h/heated in a closed vessel for a long time. Since these salts are sources of CO2 and NH3 and H2O is available from the reaction medium, adenine might get formed by the combination of CO2, H2O and NH3. The occurrence of this reaction in the gas phase as well as in the aqueous phase points towards the possibility of similar reactions during the primitive earth conditions.

Decomposition of Thiourea Dioxide under Aerobic and Anaerobic Conditions in an Aqueous Alkaline Solution

Abstract: The kinetics and mechanism of the decomposition of thiourea dioxide in an aqueous alkaline solution under aerobic and anaerobic conditions are established. It is discovered that along with the decomposition of thiourea dioxide molecules with C–S bond cleavage and the subsequent formation of sulfoxyl acid anions, there is a reversible stage of the formation of thiourea and peroxide anions. The rate constants of the indicated stages are determined via mathematical modeling using the experimental data.

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Degradation of 2-ketoarginine by guanidinobutyrase in arginine aminotransferase pathway of Brevibacterium helvolum.

Guanidinobutyrase (EC 3.5.3.7) involved in the arginine oxygenase pathway of Brevibacterium helvolum IFO 12073 was found to catalyze also the hydrolysis of 2-ketoarginine (2-keto-5-guanidinovalerate) to 2-ketoornithine (2-keto-5-aminovalerate) and urea, the second step of the arginine aminotransferase pathway. No other enzyme that degraded 2-ketoarginine was found in cells grown on L-arginine. The enzyme hydrolyzed 2-ketoarginine with a relative rate of about 0.7% of that toward 4-guanidinobutyrate. The Km for 2-ketoarginine was 33 mM.

Catalytic Urea Synthesis from Ammonium Carbamate Using a Copper(II) Complex: A Combined Experimental and Theoretical Study

The synthesis of urea fertilizer is currently the largest CO2 conversion process by volume in the industry. In this process, ammonium carbamate is an intermediate en route to urea formation. We determined that the tetraammineaquacopper(II) sulfate complex, [Cu(NH3)4(OH2)]SO4, catalyzed the formation of urea from ammonium carbamate in an aqueous solution. A urea yield of up to 18 ± 6% was obtained at 120 °C after 15 h and in a high-pressure metal reactor. No significant urea formed without the catalyst. The urea product was characterized by Fourier transform infrared (FT-IR), powder X-ray diffraction (PXRD), and quantitative 1H{13C} NMR analyses. The [Cu(NH3)4(OH2)]SO4 catalyst was then recovered at the end of the reaction in a 29% recovery yield, as verified by FT-IR, PXRD, and quantitative UV-vis spectroscopy. A precipitation method using CO2 was developed to recover and reuse 66 ± 3% of Cu(II). The catalysis mechanism was investigated by the density functional theory at the B3LYP/6-31G*? level with an SMD continuum solvent model. We determined that the [Cu(NH3)4]2+ complex is likely an effective catalyst structure. The study of the catalysis mechanism suggests that the coordinated carbamate with [Cu(NH3)4]2+ is likely the starting point of the catalyzed reaction, and carbamic acid can be involved as a transient intermediate that facilitates the removal of an OH group. Our work has paved the way for the rational design of catalysts for urea synthesis from the greenhouse gas CO2.

Unveiling Electrochemical Urea Synthesis by Co-Activation of CO2 and N2 with Mott–Schottky Heterostructure Catalysts

Electrocatalytic C?N bond coupling to convert CO2 and N2 molecules into urea under ambient conditions is a promising alternative to harsh industrial processes. However, the adsorption and activation of inert gas molecules and then the driving of the C–N coupling reaction is energetically challenging. Herein, novel Mott–Schottky Bi-BiVO4 heterostructures are described that realize a remarkable urea yield rate of 5.91 mmol h?1 g?1 and a Faradaic efficiency of 12.55 % at ?0.4 V vs. RHE. Comprehensive analysis confirms the emerging space–charge region in the heterostructure interface not only facilitates the targeted adsorption and activation of CO2 and N2 molecules on the generated local nucleophilic and electrophilic regions, but also effectively suppresses CO poisoning and the formation of endothermic *NNH intermediates. This guarantees the desired exothermic coupling of *N=N* intermediates and generated CO to form the urea precursor, *NCON*.

Catalytic hydration of cyanamides with phosphinous acid-based ruthenium(ii) and osmium(ii) complexes: scope and mechanistic insights

The synthesis of a large variety of ureas R1R2NC(O)NH2 (R1 and R2 = alkyl, aryl or H; 26 examples) was successfully accomplished by hydration of the corresponding cyanamides R1R2NCN using the phosphinous acid-based complexes [MCl2(η6-p-cymene)(PMe2OH)] (M = Ru (1), Os (2)) as catalysts. The reactions proceeded cleanly under mild conditions (40-70 °C), in the absence of any additive, employing low metal loadings (1 molpercent) and water as the sole solvent. In almost all the cases, the osmium complex 2 featured a superior reactivity in comparison to that of its ruthenium counterpart 1. In addition, for both catalysts, the reaction rates observed for the hydration of the cyanamide substrates were remarkably faster than those involving classical aliphatic and aromatic nitriles. Computational studies allowed us to rationalize all these trends. Thus, the calculations indicated that the presence of a nitrogen atom directly linked to the CN bond depopulates electronically the nitrile carbon by inductive effect when coordinated to the metal center, thus favouring the intramolecular nucleophilic attack of the OH group of the phosphinous acid ligand to this carbon. On the other hand, the higher reactivity of Os vs. Ru seems to be related with the lower ring strain on the incipient metallacycle that starts to form in the transition state associated with this key step in the catalytic cycle. Indirect experimental evidence of the generation of the metallacyclic intermediates was obtained by studying the reactivity of [RuCl2(η6-p-cymene)(PMe2OH)] (1) towards dimethylcyanamide in methanol and ethanol. The reactions afforded compounds [RuCl(η6-p-cymene)(PMe2OR)(NCNMe2)][SbF6] (R = Me (5a), Et (5b)), resulting from the alcoholysis of the metallacycle, which could be characterized by single-crystal X-ray diffraction. This journal is