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Biuret

Biuret is an organic chemical compound with the molecular C₂H₅N₃O₂, systematically named as imidodicarbonic diamide or more commonly as carbamoyl, formed by the condensation of two molecules with the loss of . It appears as a white, crystalline solid that is slightly soluble in (2 g/100 mL at 25 °C) and more soluble in hot , and decomposes upon heating at 185–190°C without . Chemically stable but hygroscopic, biuret exhibits a of about 10.17 and is incompatible with strong oxidizing agents or bases. The compound is best known for its role in the , a colorimetric used to detect and quantify proteins and in solutions by forming a violet-colored complex with (II) ions in alkaline conditions, due to its structural similarity to s. In this test, the intensity of the purple color, measured at 540 nm , correlates with concentration, making it suitable for analyzing proteins (typically 1–10 g/dL) or solubilized cell fractions, though it requires at least 1 mg/mL for detection and can be interfered with by substances like hemoproteins. Beyond analytical applications, biuret serves as a safer alternative to in feed additives, providing a slow-release source to enhance protein without the toxicity risks of high urea levels (biuret content should be limited to under 2% in fertilizers to avoid plant damage). It is also utilized as a pharmaceutical intermediate, regulator, in plastics, and component in paints and adhesives.

Chemical Characteristics

Molecular Structure and Formula

Biuret has the molecular C₂H₅N₃O₂ and can also be represented as HN(CONH₂)₂, which arises from the condensation of two molecules with the elimination of . The features a linear chain consisting of two ureido groups (-NHCONH₂) connected via a central carbonyl linkage, forming a symmetric structure with two functional groups and a urea-like -CO-NH-CO-NH- moiety. In its , the is nearly planar, with the largest torsion measuring only 3°. Key bond distances include C=O lengths of 1.23–1.24 , imide C–N bonds at 1.38 , and C–N bonds at 1.32–1.33 ; notable bond angles are N–C–N at 114–119°, C–N–C at 128°, N–C–O at 123–124°, and imide N–C–O at 118–122°. The IUPAC name for biuret is carbamoylurea, and its molecular weight is 103.09 g/mol. In the solid state, biuret crystallizes in the monoclinic system with C2/c (No. 15) and Z = 8 molecules per ; the lattice parameters are a = 15.4135(8) , b = 6.6042(3) , c = 9.3055(4) , and β = 91.463(3)°. studies reveal a bonding network featuring one intramolecular O⋯H–N at 1.92 and two intermolecular bonds, which collectively form skew ribbon motifs stabilizing the crystal packing.

Physical Properties

Biuret is a white, hygroscopic crystalline solid, often appearing as an odorless powder, pellets, or large crystals; it forms elongated plates when crystallized from and needles from aqueous solutions. The compound has a melting point of 190 °C, at which it begins to decompose. Its density is 1.467 g/cm³, measured at -5 °C. Biuret exhibits moderate solubility in water, increasing with temperature: 2.01 g/100 g at 25 °C, 7 g/100 g at 50 °C, 20 g/100 g at 75 °C, and up to 53.5 g/100 g at 105.5 °C. It is freely soluble in hot alcohol but only slightly soluble in ether. Under normal conditions, biuret is chemically stable but hygroscopic, readily absorbing moisture from the air. At elevated temperatures above approximately 193 °C, it undergoes thermal decomposition, releasing ammonia and other gaseous products such as isocyanic acid.

Chemical Properties and Reactivity

Biuret exhibits notable reactivity in forming coordination complexes with metal ions, particularly producing a violet-colored complex with ions in alkaline conditions, which is the basis for its use in qualitative analysis. This complexation arises from the deprotonated atoms coordinating to the copper center. Additionally, biuret undergoes under acidic or basic conditions, breaking down to and , a process that can be accelerated by heating under pressure. The compound demonstrates thermal instability, decomposing above 193 °C and yielding upon , which limits its handling at high temperatures. During urea production, biuret forms as an unwanted due to sensitivity to prolonged heating, often requiring controls to minimize its concentration. Biuret displays low , with an oral LD50 exceeding 14,000 mg/kg in rats, indicating minimal risk at typical exposure levels. However, biuret can be phytotoxic at concentrations exceeding approximately 1.5-2% in fertilizers, potentially causing damage to foliage and impaired growth in sensitive and seedlings, especially when applied near germinating . It is safe for digestion owing to slow microbial in the , reducing toxicity risks compared to , but can induce toxicity in non-ruminants if overdosed due to limited degradation capacity. The pKa for deprotonation of its imino groups is approximately 10.2, reflecting weak acidity. Spectroscopically, biuret is identified by infrared absorption peaks at around 1700 cm⁻¹ corresponding to the C=O stretch and 3300 cm⁻¹ for the N-H stretch, characteristic of its urea-like functional groups. These features aid in confirming its presence in mixtures.

Production

Laboratory Synthesis

The classic laboratory synthesis of biuret is achieved by heating urea to 150–160 °C for 30–60 minutes, resulting in the condensation reaction where two molecules of urea combine to form biuret and ammonia:
$2 \ \ce{NH2CONH2} \rightarrow \ce{HN(CONH2)2} + \ce{NH3}
This process requires an inert atmosphere or reduced pressure (typically 50–75 mm Hg) to remove the evolved ammonia gas and limit the formation of side products such as cyanuric acid.
Following the reaction, the crude product is purified by dissolving it in hot (or a dilute alkaline at 50–70 °C), filtering to remove insoluble impurities, and cooling the filtrate to induce of biuret as white needles or crystals, which are then filtered, washed with ice-cold , and dried at around 110 °C. An alternative laboratory route involves the reaction of with (COCl₂) or urea with cyanic acid (HNCO) to yield biuret, though the phosgene-based method is less commonly employed due to the of and is typically reserved for specialized syntheses. Under optimized conditions, this synthesis provides conversion yields of around 40% biuret (with up to 85% recovery of pure product after purification), with the primary byproduct being ammonia. Due to the release of ammonia gas during the heating step, the procedure must be conducted in a well-ventilated fume hood to ensure safety.

Industrial Production

Biuret is primarily produced as an unintended byproduct during the industrial synthesis of urea, which involves the reaction of ammonia and carbon dioxide under high pressure and temperature conditions. The standard urea manufacturing process, known as the Bosch-Meiser process, operates at pressures of 150–250 bar and temperatures of 180–210 °C, where biuret forms through the secondary condensation of urea molecules. In commercial urea production, biuret content typically ranges from 0.3% to 1.0% by weight, though it can reach up to 1.5% depending on process conditions. For applications requiring higher biuret concentrations, such as additives, it is intentionally manufactured by controlled of . This involves heating melt or employing staged heating in specialized reactors to promote , achieving biuret levels of at least 55% with residual not exceeding 15%. Feed-grade biuret is produced via or similar heat-based methods, ensuring a minimum content equivalent to 38.5% for nutrition. To meet quality standards, particularly for fertilizer-grade , biuret content is controlled and minimized through purification techniques such as under vacuum or adsorption using anion exchange resins. International specifications limit biuret to a maximum of 1.5% in prilled or granular to prevent in sensitive crops, with removal processes integrated downstream of synthesis to recycle or separate the byproduct. For high-biuret products, selective cools the urea solution to isolate biuret-rich fractions. Global production of biuret as a feed additive is tied to manufacturing capacity, with major output from facilities in the United States and , where integrated urea plants facilitate byproduct utilization. The feed non-protein nitrogen market, including biuret, was valued at approximately USD 1.32 billion in 2015 and reached USD 1.73 billion in 2024, reflecting its niche but steady demand in . Environmental management in biuret-inclusive urea production focuses on mitigating ammonia emissions from synthesis and prilling stages, primarily through scrubbers and process upgrades that capture and recycle unreacted ammonia. Best available techniques, including wet scrubbing systems, have reduced ammonia releases by up to 72% in modernized plants.

Applications

Biuret Test

The is a colorimetric employed to detect and qualitatively assess proteins in biological and chemical samples through the formation of a chelate complex between Cu²⁺ ions and the unprotonated bonds in an alkaline medium. The reaction involves the coordination of ions with the nitrogen atoms of at least two adjacent bonds (-CO-NH-), requiring compounds with a minimum of three residues for a positive response, and exhibits sensitivity for protein concentrations exceeding 5 mg/mL. The standard procedure involves adding 1–2 mL of 0.1 N NaOH to the sample to alkalinize it, followed by 1–2 mL of Biuret reagent (typically 0.95% CuSO₄ in 0.1 N NaOH stabilized with to prevent Cu(OH)₂ precipitation), mixing thoroughly, and observing the color change after 5–10 minutes of incubation at . A or coloration confirms the presence of proteins, while the solution retains its original blue hue in negative controls; can be performed by measuring at 540 against a protein standard curve. The test demonstrates specificity for and proteins due to the requirement for multiple peptide bonds to form the stable Cu²⁺ complex, distinguishing it from single or dipeptides that do not react significantly. However, potential false positives may arise from other nitrogenous compounds capable of chelating , such as EDTA or certain short peptides, though these are typically minimized by using blank controls and sample dilution. In applications, the Biuret test serves for protein detection and rough quantification in biochemistry laboratories, food analysis to evaluate nutritional content and quality, and clinical diagnostics such as assessing total serum protein levels or identifying in urine samples. Key limitations include its relatively low , which precludes detection of proteins below 5 mg/mL, and susceptibility to interference from reducing agents like ascorbic acid or detergents that alter Cu²⁺ availability; enhanced variants, such as the micro-biuret method measuring at 270 nm, address sensitivity issues for lower concentrations. The simplified reaction equation is: \text{Protein-NHCONH-} + \text{Cu}^{2+} \rightarrow [\text{Cu-Protein}] \text{ complex (violet)}

Animal Feed Additive

Biuret serves as a non-protein nitrogen (NPN) source in ruminant nutrition, particularly for cattle and sheep, where it supplies nitrogen for microbial protein synthesis in the rumen. In ruminants, rumen microbes hydrolyze biuret via biuretase enzymes to allophanate, which further breaks down to ammonia and carbon dioxide; this ammonia is then incorporated into microbial protein that passes to the lower gut for animal utilization. Feed-grade biuret provides a minimum of 35% nitrogen, equivalent to approximately 219% crude protein, though commercial formulations guarantee at least 38.5% nitrogen with up to 15% residual urea. Biuret is typically incorporated into feeds at 1–2% of the total diet, often as prilled forms for slow-release properties that mimic the gradual availability of natural proteins like . For on low-quality forages, inclusion rates of 0.1–0.2 lb per head daily support efficient delivery when blended with energy sources, while similar levels apply to sheep and on roughage diets. products, such as feed-grade biuret prills, ensure and without hygroscopic issues, facilitating mixing in range cubes or minerals up to 8–30%. As a cost-effective alternative to , biuret enhances performance by providing sustained release, reducing peak toxicity risks compared to faster-hydrolyzing NPN like . In cows, adapted feeding of biuret has improved production, with trials showing yields of 33.1 lb/day versus 29.3 lb/day on diets after periods. Overall, it supports and on low-protein forages without compromising feed efficiency. Safety profiles affirm biuret's suitability for ruminants, with U.S. FDA approval under 21 CFR 573.220 for use in all ruminant feeds, including lactating since 2003, provided nonprotein nitrogen does not exceed one-third of total crude protein and diets are balanced with carbohydrates. It offers a toxicity threshold over 20 times higher than due to slower . However, biuret is toxic to monogastrics like pigs, which lack microbes and biuretase enzymes for , potentially leading to adverse effects. Research, including 1980s trials, has established optimal inclusion rates and confirmed efficacy without toxicity in adapted ruminants; for instance, studies on sheep and demonstrated full adaptation within 15–71 days, supporting utilization comparable to true proteins while maintaining and productivity. Earlier foundational work in the 1960s–1970s, such as those evaluating biuret in low-energy diets, further validated its slow-release benefits for maintenance and .

Other Uses

Biuret serves as an impurity in urea-based fertilizers, where its concentration is strictly controlled to below 1% to prevent . Standard urea fertilizers typically contain 0.8–1.0% biuret, while low-biuret formulations limit it to 0.25% or less for sensitive applications such as or seedling establishment. Excess biuret levels above these thresholds can cause significant crop damage, including , stunted growth, and reduced yields in sensitive species like and corn; for instance, foliar applications exceeding 0.2–0.5 kg/ha have been linked to corn yield losses of up to 30%. In , biuret functions as a versatile intermediate for producing herbicides, pharmaceuticals, and polymers. Derivatives of biuret have been developed as active components in herbicidal compositions, leveraging their nitrogen-rich structure to target weed growth. In pharmaceutical applications, biuret acts as a precursor in the synthesis of certain nitrogen-containing compounds used in . For , biuret is incorporated into oligomers and resins, such as biuret-urea-formaldehyde polymers and polybiurets formed via reaction with diisocyanates, enhancing material properties like thermal stability and mechanical strength. Biuret plays a role in biochemical research, particularly in investigations of nitrogen metabolism and enzymatic processes. It is utilized in studies of purine degradation pathways, where it appears as an intermediate related to urea formation, aiding understanding of non-protein nitrogen utilization. As a substrate for biuret hydrolase enzymes, it helps elucidate mechanisms of enzyme inhibition and activity in microbial systems. In recent research from the 2020s, biuret has been central to exploring biodegradation pathways of s-triazine compounds, such as cyanuric acid, revealing insights into microbial enzymes and protein contexts that facilitate nitrogen release from pollutants. Niche applications of biuret exploit its high nitrogen content for specialized materials. In polymer-based adhesives and coatings, biuret-derived structures contribute to formulations requiring enhanced cross-linking and durability. Its nitrogen functionality also supports minor roles in flame-retardant systems, where it promotes char formation during combustion. The market for biuret remains niche, focused on specialty chemicals with production volumes far smaller than those of primary fertilizers. Primarily generated as a byproduct during urea manufacturing, its distribution is tied to fertilizer quality control, with excess amounts posing environmental risks through runoff that can exacerbate water pollution and algal blooms in agricultural watersheds.

Background

History

Biuret was first prepared and studied in 1847 by German physicist and chemist Gustav Heinrich Wiedemann (1826–1899) as part of his doctoral dissertation at the University of Berlin, where he obtained the compound by heating at high temperatures. The name "biuret" derives from the Latin prefix "bi-" (meaning two) combined with "urea," reflecting its formation from two molecules of , also known as bis-urea. Early investigations into biuret's chemical properties included observations of a characteristic color reaction with copper salts in alkaline solutions, first described in 1833 by Heinrich Rose while studying reactions of metallic salts with proteinaceous materials. This reaction was later formalized as a test for proteins by physiologist Gustaw Piotrowski in 1857, earning it the alternative name Piotrowski's test in some regions. In the 20th century, biuret gained recognition as an unintended byproduct in the industrial production of urea-based fertilizers, with concerns about its phytotoxicity emerging in the 1940s as synthetic nitrogen fertilizers proliferated post-World War II. During the 1950s and 1960s, amid global protein shortages for livestock feed, research intensified on biuret as a slow-release non-protein nitrogen source for ruminants, with key studies demonstrating its efficacy in beef cattle and sheep diets compared to urea. Significant milestones included U.S. Food and Drug Administration (FDA) approval in 1976 for biuret use in feeds for non-lactating ruminants, expanding its application in animal nutrition. More recently, in 2020, the crystal structure of biuret was refined using X-ray diffraction (XRD) analysis of single crystals grown from ethanol solution, providing deeper insights into its molecular arrangement and reactivity. Biuret is structurally derived from , the simplest member of the biuret group of compounds, with the formula \ce{(NH2)2CO} or \ce{NH2CONH2}, where biuret forms as a linear dimer through of two molecules, releasing . Triuret serves as a higher homolog of biuret, resulting from further of or biuret, and possesses the formula \ce{HN(CONH2)CONHCONH2}, extending the linear urea chain by an additional carbonyl-linked urea unit. Cyanuric acid, a cyclic trimer of with the formula \ce{(NH2CO)3} or \ce{C3H3N3O3}, often appears as a side product during biuret synthesis from or , differing from biuret's open-chain structure by forming a stable six-membered ring. Biuret also forms coordination complexes, such as the square-planar (II) biuret complex, where the metal ion binds to the nitrogen atoms of the biuret , exhibiting tetradentate coordination. Biuret is incorporated into urea-formaldehyde resins as a co-monomer, forming tripolymers that enhance resin stability and reduce formaldehyde emissions during curing, achieved by initial acid-catalyzed reaction of biuret with before urea addition. In terms of comparative properties, triuret is hygroscopic and has low in (approximately 60 mg/L at 20°C), less than biuret, while is notably insoluble in and common organic solvents, contributing to its role in flame-retardant applications through and char formation.

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    Cyanuric acid | C3N3(OH)3 | CID 7956 - PubChem
    Cyanuric acid is the enol tautomer of isocyanuric acid. It has a role as a xenobiotic. It is a member of 1,3,5-triazines and a heteroaryl hydroxy compound.