Guanidine

Last updated
Guanidine
Skeletal formula of guanidine Guanidin.svg
Skeletal formula of guanidine
Skeletal formula of guanidine with the implicit carbon shown, and all explicit hydrogens added. Guanidine-2D.png
Skeletal formula of guanidine with the implicit carbon shown, and all explicit hydrogens added.
Ball and stick model of guanidine Guanidine-3D-balls.png
Ball and stick model of guanidine
Spacefill model of guanidine Guanidine-3D-vdW.png
Spacefill model of guanidine
Names
Preferred IUPAC name
Guanidine [1]
Other names
Iminomethanediamine
Identifiers
3D model (JSmol)
506044
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.003.656 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 204-021-8
100679
MeSH Guanidine
PubChem CID
UNII
  • InChI=1S/CH5N3/c2-1(3)4/h(H5,2,3,4) Yes check.svgY
    Key: ZRALSGWEFCBTJO-UHFFFAOYSA-N Yes check.svgY
  • NC(N)=N
Properties
CH5N3
Molar mass 59.072 g·mol−1
Melting point 50 °C (122 °F; 323 K)
log P −1.251
Basicity (pKb)0.4 [2]
Conjugate acid Guanidinium
Thermochemistry
−57 – −55 kJ mol−1
−1.0511 – −1.0531 MJ mol−1
Pharmacology
Pharmacokinetics:
7–8 hours
Hazards
Lethal dose or concentration (LD, LC):
475 mg/kg (oral, rat) [3]
Related compounds
Related compounds
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 ?)

Guanidine is the compound with the formula HNC(NH2)2. It is a colourless solid that dissolves in polar solvents. It is a strong base that is used in the production of plastics and explosives. It is found in urine predominantly in patients experiencing renal failure. [4] A guanidine moiety also appears in larger organic molecules, including on the side chain of arginine.

Contents

Structure

Guanidine can be thought of as a nitrogenous analogue of carbonic acid. That is, the C=O group in carbonic acid is replaced by a C=NH group, and each OH is replaced by a NH
2
group. [5] Isobutene can be seen as the carbon analogue in much the same way. A detailed crystallographic analysis of guanidine was elucidated 148 years after its first synthesis, despite the simplicity of the molecule. [6] In 2013, the positions of the hydrogen atoms and their displacement parameters were accurately determined using single-crystal neutron diffraction. [7]

Production

Guanidine can be obtained from natural sources, being first isolated in 1861 by Adolph Strecker via the oxidative degradation of an aromatic natural product, guanine, isolated from Peruvian guano. [8] [9]

A laboratory method of producing guanidine is gentle (180-190 °C) thermal decomposition of dry ammonium thiocyanate in anhydrous conditions:

3 NH4SCN → 2 CH5N3 + H2S + CS2

The commercial route involves a two step process starting with the reaction of dicyandiamide with ammonium salts. Via the intermediacy of biguanidine, this ammonolysis step affords salts of the guanidinium cation (see below). In the second step, the salt is treated with base, such as sodium methoxide. [8]

Isothiouronium salts (S-alkylated thioureas) react with amines to give guanidinium salts: [10]

RNH2 + [CH3SC(NH2)2]+X → [RN(H)C(NH2)2]+X + CH3SH

The resulting guanidinium ions can often be deprotonated to give the guanidine. This approach is sometimes called the Rathke synthesis, in honor of its discoverer. after Bernhard Rathke [11] [12]

Chemistry

Guanidinium cation

The conjugate acid is called the guanidinium cation, (C(NH
2
)+
3
). This planar, symmetric ion consists of three amino groups each bonded to the central carbon atom with a covalent bond of order 4/3. It is a highly stable +1 cation in aqueous solution due to the efficient resonance stabilization of the charge and efficient solvation by water molecules. As a result, its pKaH is 13.6 [2] (pKb of 0.4) meaning that guanidine is a very strong base in water; in neutral water, it exists almost exclusively as guanidinium. Due to this, most guanidine derivatives are salts containing the conjugate acid.

Testing for guanidine

Guanidine can be selectively detected using sodium 1,2-naphthoquinone-4-sulfonic acid (Folin's reagent) and acidified urea. [13]

Uses

Industry

The main salt of commercial interest is the nitrate [C(NH
2
)3]NO
3
. It is used as a propellant, for example in air bags.

Medicine

Since the Middle Ages in Europe, guanidine has been used to treat diabetes as the active antihyperglycemic ingredient in French lilac. Due to its long-term hepatotoxicity, further research for blood sugar control was suspended at first after the discovery of insulin. Later development of nontoxic, safe biguanides led to the long-used first-line diabetes control medicine metformin, introduced to Europe in the 1950s & United States in 1995 and now prescribed to over 17 million patients per year in the US. [14] [15]

Guanidinium chloride [14] is a now-controversial adjuvant in treatment of botulism. Recent studies have shown some significant subsets of patients who see no improvement after the administration of this drug. [16]

Biochemistry

Guanidine exists protonated, as guanidinium, in solution at physiological pH.

Guanidinium chloride (also known as guanidine hydrochloride) has chaotropic properties and is used to denature proteins. Guanidinium chloride is known to denature proteins with a linear relationship between concentration and free energy of unfolding. In aqueous solutions containing 6  M guanidinium chloride, almost all proteins lose their entire secondary structure and become randomly coiled peptide chains. Guanidinium thiocyanate is also used for its denaturing effect on various biological samples.

Recent studies suggest that guanidinium is produced by bacteria as a toxic byproduct. To alleviate the toxicity of guanidinium, bacteria have developed a class of transporters known as guanidinium exporters or Gdx proteins to expel the extra amounts of this ion to the outside of the cell. [17] Gdx proteins, are highly selective for guanidinium and mono-substituted guanidinyl compounds and share an overlapping set of non-canonical substrates with drug exporter EmrE. [18]

Other

Guanidinium hydroxide is the active ingredient in some non-lye hair relaxers.

Guanidine derivatives

The general structure of a guanidine Guanidine-group-2D-skeletal.png
The general structure of a guanidine

Guanidines are a group of organic compounds sharing a common functional group with the general structure (R
1
R
2
N)(R
3
R
4
N)C=N−R
5
. The central bond within this group is that of an imine, and the group is related structurally to amidines and ureas. Examples of guanidines are arginine, triazabicyclodecene, saxitoxin, and creatine.

Galegine is an isoamylene guanidine. [19]

See also

Related Research Articles

<span class="mw-page-title-main">Amine</span> Chemical compounds and groups containing nitrogen with a lone pair (:N)

In chemistry, amines are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Formally, amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines, trimethylamine, and aniline. Inorganic derivatives of ammonia are also called amines, such as monochloramine.

Urea, also called carbamide, is an organic compound with chemical formula CO(NH2)2. This amide has two amino groups joined by a carbonyl functional group. It is thus the simplest amide of carbamic acid.

<span class="mw-page-title-main">Hydroxylamine</span> Inorganic compound

Hydroxylamine is an inorganic compound with the chemical formula NH2OH. The compound is in a form of a white hygroscopic crystals. Hydroxylamine is almost always provided and used as an aqueous solution. It is consumed almost exclusively to produce Nylon-6. The oxidation of NH3 to hydroxylamine is a step in biological nitrification.

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">Carbamate</span> Chemical group (>N–C(=O)–O–)

In organic chemistry, a carbamate is a category of organic compounds with the general formula R2NC(O)OR and structure >N−C(=O)−O−, which are formally derived from carbamic acid. The term includes organic compounds, formally obtained by replacing one or more of the hydrogen atoms by other organic functional groups; as well as salts with the carbamate anion H2NCOO.

A chaotropic agent is a molecule in water solution that can disrupt the hydrogen bonding network between water molecules. This has an effect on the stability of the native state of other molecules in the solution, mainly macromolecules by weakening the hydrophobic effect. For example, a chaotropic agent reduces the amount of order in the structure of a protein formed by water molecules, both in the bulk and the hydration shells around hydrophobic amino acids, and may cause its denaturation.

In chemistry, a trimer is a molecule or polyatomic anion formed by combination or association of three molecules or ions of the same substance. In technical jargon, a trimer is a kind of oligomer derived from three identical precursors often in competition with polymerization.

<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.

<span class="mw-page-title-main">Diazonium compound</span> Group of organonitrogen compounds

Diazonium compounds or diazonium salts are a group of organic compounds sharing a common functional group [R−N+≡N]X where R can be any organic group, such as an alkyl or an aryl, and X is an inorganic or organic anion, such as a halide. The parent compound where R is hydrogen, is diazenylium.

The Reformatsky reaction is an organic reaction which condenses aldehydes or ketones with α-halo esters using metallic zinc to form β-hydroxy-esters:

<span class="mw-page-title-main">Isocyanic acid</span> Chemical compound (H–N=C=O)

Isocyanic acid is a chemical compound with the structural formula HNCO, which is often written as H−N=C=O. It is a colourless, volatile and poisonous substance, with a boiling point of 23.5 °C. It is the predominant tautomer and an isomer of cyanic acid (aka. cyanol).

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

Guanidinium thiocyanate(GTC) or guanidinium isothiocyanate (GITC) is a chemical compound used as a general protein denaturant, being a chaotropic agent, although it is most commonly used as a nucleic acid protector in the extraction of DNA and RNA from cells.

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

Biguanide is the organic compound with the formula HN(C(NH)NH2)2. It is a colorless solid that dissolves in water to give a highly basic solution. These solutions slowly hydrolyse to ammonia and urea.

<span class="mw-page-title-main">Ortho ester</span> Chemical group with the structure RC(OR)3

In organic chemistry, an ortho ester is a functional group containing three alkoxy groups attached to one carbon atom, i.e. with the general formula RC(OR′)3. Orthoesters may be considered as products of exhaustive alkylation of unstable orthocarboxylic acids and it is from these that the name 'ortho ester' is derived. An example is ethyl orthoacetate, CH3C(OCH2CH3)3, more correctly known as 1,1,1-triethoxyethane.

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

Guanidinium chloride or guanidine hydrochloride, usually abbreviated GdmCl and sometimes GdnHCl or GuHCl, is the hydrochloride salt of guanidine.

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

Acetylenedicarboxylic acid or butynedioic acid is an organic compound with the formula H2C4O4 or HO−C(=O)−C≡C−C(=O)−OH. It is a crystalline solid that is soluble in diethyl ether.

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

In organic chemistry, isothiouronium is a functional group with the formula [RSC(NH2)2]+ (R = alkyl, aryl) and is the acid salt of isothiourea. The H centres can also be replaced by alkyl and aryl. Structurally, these cations resemble guanidinium cations. The CN2S core is planar and the C–N bonds are short.

<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">Diamidophosphate</span> Chemical compound

Diamidophosphate (DAP) is the simplest phosphorodiamidate ion, with formula PO2(NH2)2. It is a phosphorylating ion and was first used for the phosphorylation of sugars in aqueous medium. DAP has attracted interest in the area of primordial chemistry.

Acetamidine hydrochloride is an organic compound with the formula CH3C(NH)NH2·HCl, used in the synthesis of many nitrogen-bearing compounds. It is the hydrochloride of acetamidine, one of the simplest amidines.

References

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