Cyanamide

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Cyanamide
Cyanamide.svg
Cyanamide (nitrile) 3D spacefill.png
Cyanamide (diimide) 3D spacefill.png
Names
IUPAC name
Cyanamide
Other names
Amidocyanogen, carbamonitrile, carbimide, carbodiimide, cyanoamine, cyanoazane, N-cyanoamine, cyanogenamide, cyanogen amide, cyanogen nitride, diiminomethane, hydrogen cyanamide, methanediimine
Identifiers
3D model (JSmol)
3DMet
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.006.358 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 206-992-3
784
KEGG
PubChem CID
RTECS number
  • GS5950000
UNII
UN number 2811
  • InChI=1S/CH2N2/c2-1-3/h2H2 Yes check.svgY
    Key: XZMCDFZZKTWFGF-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/CH2N2/c2-1-3/h2H2
    Key: XZMCDFZZKTWFGF-UHFFFAOYAW
Properties
CH2N2
Molar mass 42.040 g/mol
AppearanceCrystalline solid
Density 1.28 g/cm3
Melting point 44 °C (111 °F; 317 K)
Boiling point 260 °C (500 °F; 533 K) (decomposes)
83 °C at 6.7 Pa
140 °C at 2.5 kPa
85 g/100 ml (25 °C)
Solubility in organic solventssoluble
log P -0.82
Acidity (pKa)10.3 [1]
Hazards
GHS labelling:
GHS-pictogram-acid.svg GHS-pictogram-skull.svg GHS-pictogram-exclam.svg GHS-pictogram-silhouette.svg
Danger
H301, H311, H314, H317, H351, H361, H373, H412
P201, P202, P260, P261, P264, P270, P272, P273, P280, P281, P301+P310, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P308+P313, P310, P312, P314, P321, P322, P330, P333+P313, P361, P363, P405, P501
NFPA 704 (fire diamond)
NFPA 704.svgHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 2: Undergoes violent chemical change at elevated temperatures and pressures, reacts violently with water, or may form explosive mixtures with water. E.g. white phosphorusSpecial hazards (white): no code
2
1
2
Flash point 141 °C (286 °F; 414 K)
NIOSH (US health exposure limits):
PEL (Permissible)
none [2]
REL (Recommended)
TWA 2 mg/m3
IDLH (Immediate danger)
N.D. [2]
Safety data sheet (SDS) ICSC 0424
Related compounds
Related compounds
 Calcium cyanamide
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Cyanamide is an organic compound with the formula C N 2 H 2. This white solid is widely used in agriculture and the production of pharmaceuticals and other organic compounds. It is also used as an alcohol-deterrent drug. The molecule features a nitrile group attached to an amino group. Derivatives of this compound are also referred to as cyanamides, the most common being calcium cyanamide (CaCN2). [3]

Contents

Tautomers and self-condensations

Containing both a nucleophilic and electrophilic site within the same molecule, cyanamide undergoes various reactions with itself. Cyanamide exists as two tautomers, one with the connectivity N≡C–NH2 and the other with the formula HN=C=NH ("carbodiimide" tautomer). The N≡C–NH2 form dominates, but in a few reactions (e.g. silylation) the diimide form appears to be important. [3]

Cyanamide dimerizes to give 2-cyanoguanidine (dicyandiamide). This dimerization is hindered or reversed by acids and is inhibited by low temperatures. The cyclic trimer is called melamine. [3]

Production

Cyanamide is produced by hydrolysis of calcium cyanamide, which in turn is prepared from calcium carbide via the Frank-Caro process. [4]

CaCN2 + H2O + CO2 → CaCO3 + H2NCN

The conversion is conducted on slurries.

Reactions and uses

Cyanamide can be regarded as a functional single carbon fragment which can react as an electrophile or nucleophile. The main reaction exhibited by cyanamide involves additions of compounds containing an acidic proton. Water, hydrogen sulfide, and hydrogen selenide react with cyanamide to give urea, thiourea, and selenourea, respectively:

H2NCN + H2E → H2NC(E)NH2 (E = O, S, Se)

In this way, cyanamide behaves as a dehydration agent and thus can induce condensation reactions. Alcohols, thiols, and amines react analogously to give alkylisoureas, isothioureas, and guanidines. The anti-ulcer drug cimetidine is generated using such reactivity. Related reactions exploit the bifunctionality of cyanamide to give heterocycles, and this latter reactivity is the basis of several pharmaceutical syntheses such as the aminopyrimidine imatinib, and agrichemicals Amitrol and hexazinone. The hair-loss treatment minoxidil and the anthelmintics albendazole, flubendazole, and mebendazole feature 2-aminoimidazole substructures derived from cyanamide. [3] Cyanamide is also used in the synthesis of other pharmaceutical drugs including tirapazamine, etravirine, revaprazan, and dasantafil.

The cyanamide anion has the character of a pseudo chalcogen, cyanamide can therefore be regarded as analogue to water or hydrogen sulfide.

A convenient method for the preparation of secondary amines which are not contaminated with primary or tertiary amines is the reaction of cyanamide with alkyl halides to N,N-dialkylcyanamides which can easily be hydrolyzed to dialkylamines and then decarboxylated. [5] Cyanamide adds itself in the presence of N-bromosuccinimide to olefinic double bonds. The addition product is converted by bases to N-Cyanaziridine, [6] cyclized in the presence of acids to imidazolines, which can be further reacted to vicinal diamines by alkaline cleavage. [7]

Cyanamide is also a versatile synthetic building block for heterocycles: it forms 2-aminobenzimidazole with 1,2-diaminobenzene [8] and it forms with the readily available cyclic enamine 4-(1-cyclohexenyl)morpholine [9] and with elemental sulfur a 2-aminothiazole in good yields. [10]

Sodium dicyanamide is available in good yield and high purity from cyanamid and cyanogen chloride, [11] [12] which is suitable as an intermediate for the synthesis of active pharmaceutical ingredients. [13] A guanidino group is introduced by reaction of cyanamide with sarcosine In the industrial synthesis of creatine: [14] .

reaction equation Creatine synthesis.svg
reaction equation

This synthesis route mostly avoids problematic impurities like chloroacetic acid, iminodiacetic acid, or dihydrotriazine that occur in other routes. The physiological precursor guanidinoacetic is obtained analogously by reacting cyanamide with glycine.

Methods to stabilize cyanamidefmel make it available on an industrial scale. Due to the strong affinity towards self-condensation in alkaline media (see above) solutions of cyanamide are stabilized by the addition of 0.5 wt% of monosodium phosphate as buffer. Solid cyanamide is produced by careful evaporation of the solvent and subsequent addition of a hydrolysis-labile ester of formic acid. The ester absorbs traces of moisture (suppression of urea formation), neutralizes alkalinity (ammonia) and continually releases small amounts of formic acid. [15]

Agricultural use

Cyanamide, under the trade name Dormex, is a common agricultural rest-breaking agent applied in spring to stimulate uniform opening of buds, early foliation and bloom. Cyanamide can effectively compensate for the moderate lack of chilling units accumulated in the previous autumn and save the harvest that would otherwise be lost. It is particularly effective for woody plants such as blueberries, grapes, apples, peaches and kiwifruit. Most recently the product was approved for use on almonds and pistachios in the USA. Overdosage, high concentration and error in timing of application can damage the buds (especially of peach trees). [16] Growers may avoid damage by applying 30 days prior to bud break according to the label.

A 50% aqueous solution of cyanamide is also used as a biocide (disinfectant) particularly in pig farming, because it effectively kills salmonella and shigella and fights flies in all stages of development. [17]

Environmental aspects

Cyanamide degrades via hydrolysis to urea, an excellent fertilizer. Fungi, like Myrothecium verrucaria , accelerate this process utilizing the enzyme cyanamide hydratase. [18]

Cyanamide functional group

Cyanamide is the name for a functional group with the formula R1R2N−C≡N where R1 and R2 can be a variety of groups. These compounds are called cyanamides. One example is naphthylcyanamide, C10H7N(CH3)CN, which has been produced by the von Braun reaction, [19] a general method for the conversion of tertiary amines to cyanamides using cyanogen bromide as reagent. [20] Some cyanamides where R1 and R2 are identical alkyl groups are prepared directly by alkylation of a salt of the parent cyanamide. [11]

Cyanamide in space

Due to its high permanent dipole moment (i.e., 4.32 ± 0.08 D), [21] cyanamide was detected in spectral emissions coming from the Sgr B2 molecular cloud (T < 100 K) through its microwave transitions as the first known interstellar molecule containing the NCN frame. [22]

Safety

It is used as an alcohol-deterrent drug in Canada, Europe, and Japan. [3]

Cyanamide has a modest toxicity in humans. [23] Workplace exposure to hydrogen cyanamide sprays or exposure in people living in the vicinity of spraying have been reported as causing respiratory irritation, contact dermatitis, headache, and gastrointestinal symptoms of nausea, vomiting, or diarrhea. [23]

Related Research Articles

<span class="mw-page-title-main">Amide</span> Organic compounds of the form RC(=O)NR′R″

In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula R−C(=O)−NR′R″, where R, R', and R″ represent any group, typically organyl groups or hydrogen atoms. The amide group is called a peptide bond when it is part of the main chain of a protein, and an isopeptide bond when it occurs in a side chain, as in asparagine and glutamine. It can be viewed as a derivative of a carboxylic acid with the hydroxyl group replaced by an amine group ; or, equivalently, an acyl (alkanoyl) group joined to an amine group.

<span class="mw-page-title-main">Ketone</span> Organic compounds of the form >C=O

In organic chemistry, a ketone is an organic compound with the structure R−C(=O)−R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group −C(=O)−. The simplest ketone is acetone, with the formula (CH3)2CO. Many ketones are of great importance in biology and in industry. Examples include many sugars (ketoses), many steroids, and the solvent acetone.

<span class="mw-page-title-main">Hydrazone</span> Organic compounds - Hydrazones

Hydrazones are a class of organic compounds with the structure R1R2C=N−NH2. They are related to ketones and aldehydes by the replacement of the oxygen =O with the =N−NH2 functional group. They are formed usually by the action of hydrazine on ketones or aldehydes.

<span class="mw-page-title-main">Imine</span> Organic compound or functional group containing a C=N bond

In organic chemistry, an imine is a functional group or organic compound containing a carbon–nitrogen double bond. The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bonds. Imines are common in synthetic and naturally occurring compounds and they participate in many reactions.

In organic chemistry, a nitrile is any organic compound that has a −C≡N functional group. The name of the compound is composed of a base, which includes the carbon of the −C≡N, suffixed with "nitrile", so for example CH3CH2C≡N is called "propionitrile". The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, including methyl cyanoacrylate, used in super glue, and nitrile rubber, a nitrile-containing polymer used in latex-free laboratory and medical gloves. Nitrile rubber is also widely used as automotive and other seals since it is resistant to fuels and oils. Organic compounds containing multiple nitrile groups are known as cyanocarbons.

<span class="mw-page-title-main">Acyl halide</span> Oxoacid compound with an –OH group replaced by a halogen

In organic chemistry, an acyl halide is a chemical compound derived from an oxoacid by replacing a hydroxyl group with a halide group.

<span class="mw-page-title-main">Diazomethane</span> Simplest diazo compound and methylating agent

Diazomethane is an organic chemical compound with the formula CH2N2, discovered by German chemist Hans von Pechmann in 1894. It is the simplest diazo compound. In the pure form at room temperature, it is an extremely sensitive explosive yellow gas; thus, it is almost universally used as a solution in diethyl ether. The compound is a popular methylating agent in the laboratory, but it is too hazardous to be employed on an industrial scale without special precautions. Use of diazomethane has been significantly reduced by the introduction of the safer and equivalent reagent trimethylsilyldiazomethane.

Hydantoin, or glycolylurea, is a heterocyclic organic compound with the formula CH2C(O)NHC(O)NH. It is a colorless solid that arises from the reaction of glycolic acid and urea. It is an oxidized derivative of imidazolidine. In a more general sense, hydantoins can refer to groups or a class of compounds with the same ring structure as the parent compound. For example, phenytoin (mentioned below) has two phenyl groups substituted onto the number 5 carbon in a hydantoin molecule.

<span class="mw-page-title-main">Thiourea</span> Organosulfur compound (S=C(NH2)2)

Thiourea is an organosulfur compound with the formula SC(NH2)2 and the structure H2N−C(=S)−NH2. It is structurally similar to urea, except that the oxygen atom is replaced by a sulfur atom ; however, the properties of urea and thiourea differ significantly. Thiourea is a reagent in organic synthesis. Thioureas are a broad class of compounds with the general structure R2N−C(=S)−NR2.

<span class="mw-page-title-main">Amidine</span> Organic compounds

Amidines are organic compounds with the functional group RC(NR)NR2, where the R groups can be the same or different. They are the imine derivatives of amides (RC(O)NR2). The simplest amidine is formamidine, HC(=NH)NH2.

<i>N</i>,<i>N</i>-Dicyclohexylcarbodiimide Chemical compound

N,N′-Dicyclohexylcarbodiimide (DCC or DCCD) is an organic compound with the chemical formula (C6H11N)2C. It is a waxy white solid with a sweet odor. Its primary use is to couple amino acids during artificial peptide synthesis. The low melting point of this material allows it to be melted for easy handling. It is highly soluble in dichloromethane, tetrahydrofuran, acetonitrile and dimethylformamide, but insoluble in water.

<span class="mw-page-title-main">Carbodiimide</span> Class of organic compounds with general structure RN=C=NR

In organic chemistry, a carbodiimide is a functional group with the formula RN=C=NR. On Earth they are exclusively synthetic, but in interstellar space the parent compound HN=C=NH has been detected by its maser emissions.

α-Halo ketone

In organic chemistry, an α-halo ketone is a functional group consisting of a ketone group or more generally a carbonyl group with an α-halogen substituent. α-Halo ketones are alkylating agents. Prominent α-halo ketones include phenacyl bromide and chloroacetone.

<span class="mw-page-title-main">Ethylamine</span> Chemical compound

Ethylamine, also known as ethanamine, is an organic compound with the formula CH3CH2NH2. This colourless gas has a strong ammonia-like odor. It condenses just below room temperature to a liquid miscible with virtually all solvents. It is a nucleophilic base, as is typical for amines. Ethylamine is widely used in chemical industry and organic synthesis.

<span class="mw-page-title-main">Diethylamine</span> Chemical compound

Diethylamine is an organic compound with the formula (CH3CH2)2NH. It is a secondary amine. It is a flammable, weakly alkaline liquid that is miscible with most solvents. It is a colorless liquid, but commercial samples often appear brown due to impurities. It has a strong ammonia-like odor.

<span class="mw-page-title-main">Thioureas</span> Organosulfur compounds with an >NC(=S)N< structure

In organic chemistry, thioureas are members of a family of organosulfur compounds with the formula S=C(NR2)2 and structure R2N−C(=S)−NR2. The parent member of this class of compounds is thiourea. Substituted thioureas are found in several commercial chemicals.

Stephen aldehyde synthesis, a named reaction in chemistry, was invented by Henry Stephen (OBE/MBE). This reaction involves the preparation of aldehydes (R-CHO) from nitriles (R-CN) using tin(II) chloride (SnCl2), hydrochloric acid (HCl) and quenching the resulting iminium salt ([R-CH=NH2]+Cl−) with water (H2O). During the synthesis, ammonium chloride is also produced.

<span class="mw-page-title-main">4-Nitroaniline</span> Chemical compound

4-Nitroaniline, p-nitroaniline or 1-amino-4-nitrobenzene is an organic compound with the formula C6H6N2O2. A yellow solid, it is one of three isomers of nitroaniline. It is an intermediate in the production of dyes, antioxidants, pharmaceuticals, gasoline, gum inhibitors, poultry medicines, and as a corrosion inhibitor.

<span class="mw-page-title-main">Imidoyl chloride</span>

Imidoyl chlorides are organic compounds that contain the functional group RC(NR')Cl. A double bond exist between the R'N and the carbon centre. These compounds are analogues of acyl chloride. Imidoyl chlorides tend to be highly reactive and are more commonly found as intermediates in a wide variety of synthetic procedures. Such procedures include Gattermann aldehyde synthesis, Houben-Hoesch ketone synthesis, and the Beckmann rearrangement. Their chemistry is related to that of enamines and their tautomers when the α hydrogen is next to the C=N bond. Many chlorinated N-heterocycles are formally imidoyl chlorides, e.g. 2-chloropyridine, 2, 4, and 6-chloropyrimidines.

<span class="mw-page-title-main">Isatoic anhydride</span> Chemical compound

Isatoic anhydride is an organic compound derived from anthranilic acid. A white solid, it is prepared by reaction of anthranilic acid with phosgene.

References

  1. ↑ "Cyanamide_msds".
  2. 1 2 NIOSH Pocket Guide to Chemical Hazards. "#0160". National Institute for Occupational Safety and Health (NIOSH).
  3. 1 2 3 4 5 Thomas Güthner; Bernd Mertschenk (2006). Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a08_139.pub2. ISBN   978-3527306732.
  4. ↑ Kurzer, Frederick; Lawson, Alexander (1954). "Methylisourea Hydrochloride". Organic Syntheses. 34: 67. doi:10.15227/orgsyn.034.0067.
  5. ↑ Jonczyk A, Ochal Z, Makosza M (1978). "Reactions of Organic Anions; LXXXV1. Catalytic Two-Phase Alkylation of Cyanamide". Synthesis . 1978 (12): 882–883. doi:10.1055/s-1978-24922.
  6. ↑ Ponsold K, Ihn W (1970). "Die Addition von cyanamid und Halogen an Olefine ein neues Verfahren zur Darstellung von vic.-Halogencyanaminen und Aziridinen". Tetrahedron Lett. 11 (13): 1125–1128. doi:10.1016/S0040-4039(01)97925-0. PMID   5439242.
  7. ↑ Kohn, Harold; Jung, Sang Hun (1983). "New stereoselective method for the preparation of vicinal diamines from olefins and cyanamide". Journal of the American Chemical Society. 105 (12): 4106–4108. doi:10.1021/ja00350a068..
  8. ↑ Weiss, Stefan; Michaud, Horst; Prietzel, Horst; Krommer, Helmut (1973). "A New, Simple Synthesis of 2-Aminobenzimidazole". Angewandte Chemie International Edition in English. 12 (10): 841. doi:10.1002/anie.197308411..
  9. ↑ S. Hünig, E. Lücke, and W. Brenninger (1961). "1-Morpholino-1-Cyclohexene". Organic Syntheses : 65. doi:10.15227/orgsyn.041.0065 {{cite journal}}: CS1 maint: multiple names: authors list (link).
  10. ↑ Gewald, K.; Spies, H.; Mayer, R. (1970). "Zur Reaktion von Enaminen mit Schwefel und Cyanamid" [On the Reaction of Enamines with Sulfur and Cyanamide]. Journal für Praktische Chemie. 312 (5): 776–779. doi:10.1002/prac.19703120507..
  11. 1 2 E. B. Vliet (1925). "Diallylcyanamide". Organic Syntheses. 5: 45. doi:10.15227/orgsyn.005.0045.
  12. ↑ Verfahren zur Herstellung von Natrium-Dicyanamid, veröffentlicht am 10. August 2000, Anmelder: SKW Trostberg AG.
  13. ↑ "Sodium dicyanamide (Na-dicyanamide)". lonza.com. Archived from the original on 2013-05-23. Retrieved 2019-07-01.
  14. ↑ Deutsche Offenlegungsschrift DE-OS 10 2006 016 227 A1, Offenlegungsdatum: 11. Oktober 2007, Anmelder: Degussa GmbH
  15. ↑ Wehrstedt, Klaus-Dieter; Wildner, Werner; Güthner, Thomas; Holzrichter, Klaus; Mertschenk, Bernd; Ulrich, Armin (2009-10-30). "Safe transport of cyanamide". Journal of Hazardous Materials. 170 (2–3): 829–835. doi:10.1016/j.jhazmat.2009.05.043. ISSN   0304-3894. PMID   19505756.
  16. ↑ Powell, A. (1999). "Action Program for Dormex Application on Peaches". Auburn University. Archived from the original on 2018-06-20.
  17. ↑ "ALZOGUR®". AlzChem (in German). Retrieved 2019-07-01.
  18. ↑ Stransky H, Amberger A (1973). "Isolierung und eigenschaften einer Cyanamid-hydratase (E.C.-Gruppe 4. 2.1.) aus Myrothecium verrucaria Alb. u. Schw" [Isolation and properties of a cyanamide hydratase (EC 4.2.1) from Myrothecium verrucaria]. Z. Pflanzenphysiol. 70: 74–87. doi:10.1016/S0044-328X(73)80049-2.
  19. ↑ Homer W. J. Cressman (1947). "N-Methyl-1-Naphthylcyanamide". Organic Syntheses. 27: 56. doi:10.15227/orgsyn.027.0056.
  20. ↑ March, Jerry (1992), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (4th ed.), New York: Wiley, p. 436–7, ISBN   0-471-60180-2
  21. ↑ Tyler, J.K.; Sheridan, J.; Costain, C.C. (August 1972). "The microwave spectra of cyanamide". Journal of Molecular Spectroscopy. 43 (2): 248–261. doi:10.1016/0022-2852(72)90021-5.
  22. ↑ Turner, B. E.; Liszt, H. S.; Kaifu, N.; Kisliakov, A. G. (November 1975). "Microwave detection of interstellar cyanamide". The Astrophysical Journal. 201: L149. Bibcode:1975ApJ...201L.149T. doi:10.1086/181963.
  23. 1 2 Schep L, Temple W, Beasley M (January 2009). "The adverse effects of hydrogen cyanamide on human health: an evaluation of inquiries to the New Zealand National Poisons Centre". Clinical Toxicology . 47 (1). Philadelphia, PA: 58–60. doi:10.1080/15563650802459254. PMID   18951270. S2CID   6961576.
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