guanidine

Absorption

Rapidly absorbed and distributed

Toxicity

LD50 = 475 mg/kg (oral, rat). Can cause severe gastrointestinal symptoms (nausea, vomiting and diarrhea), bone marrow suppression, renal insufficiency and other hematologic abnormalities (anemia, leucopenia). Severe guanidine intoxication is characterized by nervous hyperirritability, fibrillary tremors and convulsive contractions of muscle, salivation, vomiting, diarrhea, hypoglycemia, and circulatory disturbances.

Description

Guanidine is a small, nitrogen-rich organic compound found in nature in plants (e.g., rice hulls and turnip juice) and animals (e.g., mussels and earthworms). Unlike its oxygen analogue, carbonic acid, it exists at ambient conditions (i.e., not in solution nor at cryogenic temperatures). Guanidine should not be confused with guanine, a purine derivative that is found in bat and bird feces.
Many literature sources state that guanine is very soluble in water; but, as shown in the fast facts table, it is only slightly soluble. It is, however, very hygroscopic. Its hydrochloride salt is highly water-soluble and is the usual article of commerce. The free base is extremely toxic, as shown in the hazard information table.?
Guanidine was discovered in nature in the late 19th century. In 1907, a German patent was awarded to Italian chemist Celso Ulpiani for the reaction of dicyanamide with strong acid to produce guanidine (actually, guanidinium) nitrate. Twenty-four years later, G.B.L. Smith, V. J. Sabetta, and O. F. Steinbach, Jr., at the Polytechnic Institute of Brooklyn (now New York University Tandon School of Engineering) published a comprehensive study of the conversion of dicyandiamide (aka 2-cyanoguanidine) to guanidinium nitrate and then to nitroguanidine, a powerful explosive.
Guanidine’s hydrothiocyanate salt has an interesting connection to the current COVID-19 pandemic. This past June, the US Food and Drug Administration warned laboratories not to use media that contain the thiocyanate salt or other guanidine-based chemicals to transport COVID-19 samples. The reason: Guanidine compounds can decompose to highly toxic hydrogen cyanide (HCN) gas. The FDA also advised that when personnel do not know the ingredients of a transport medium, they should handle it as though it contained a guanidine product. As of the date of FDA’s warning, no HCN-related injuries had been reported to the agency.

Chemical properties

Colorless crystals. Soluble inwater and alcohol. Combustible. Guanidine is a strong monobasic Bronsted base, which absorbs water and carbon dioxide from the air and forms strongly alkaline solutions with water and alcohols; the pH of a 20 wt % aqueous solution is ca. 13.5 (25 ℃). In aqueous solution at elevated temperature guanidine is hydrolyzed to urea; airtight alcohol solutions are stable. Guanidine is infinitely soluble in water, ethanol, methanol, and dimethylformamide.

The Uses of guanidine

Guanidine is an intermediate in synthesizing N-Formylguanidine (F700505), which is used in the preparation of Amiloride (A578700), a sodium channel blocker used as a diuretic drug.

The Uses of guanidine

Organic synthesis

Indications

For the reduction of the symptoms of muscle weakness and easy fatigability associated with the myasthenic syndrome of Eaton-Lambert. It is not indicated for treating myasthenia gravis.

Background

A strong organic base existing primarily as guanidium ions at physiological pH. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC.

Production Methods

Guanidine is formed (1) by heating ammonium thiocyanate to 180 °C, (2) by ammonolysis of orthocarbonates, C(OC2H5)4 + 3NH3 → (NH2)2C=NH + 4C2H5OH, (3) by ammonolysis of chloropicrin, Cl3CNO2 + 7NH3 → NH2)2 C=NH + 3NH4Cl + N2 + 3H2O, (4) by ammonolysis of cyanogen chloride, ClCN + NH3 → ClC(NH2)=NH → HN=C=NH → (NH2)2 C=NH.
Guanidine forms salts with acids, e.g., guanidine nitrate, HNC(NH2)2 · HNO3. By heating at 120 °C for several hours, a mixture of ammonium thiocyanate and dicyanodiamide, guanidine thiocyanate solution is obtained by extracting with water. Treating guanidine with a mixture of nitric and sulfuric acids forms nitroguanidine which is reduced by zinc and acetic acid to aminoguanidine.
By treating aminoguanidine (1) with dilute acid or alkali, there is obtained, first, semicarbazide, finally hydrazine; (2) with nitrous acid, diazoguanidine which is decomposed by alkali into alkali azide (e.g., NaN3) plus cyanamide (H2N·CN) plus water.

Definition

ChEBI: Guanidine is an aminocarboxamidine, the parent compound of the guanidines. It is a one-carbon compound, a member of guanidines and a carboxamidine. It is a conjugate base of a guanidinium.

Agricultural Uses

Carbamidine is another name for guanidine. It is a crystalline basic compound related to urea. It forms a number of salts which are used as fertilizers. Guanidine phosphate is an example.

Pharmacokinetics

Guanidine apparently acts by enhancing the release of acetylcholine following a nerve impulse. It also appears to slow the rates of depolarization and repolarization of muscle cell membranes.

Metabolism

Not metabolized.

Purification Methods

Crystallise it from water/EtOH under nitrogen. It is very deliquescent and absorbs CO2 from the air readily. [Jones Trans Faraday Soc 55 524 1959, Beilstein 3 H 82, 3 I 39, 3 II 69, 3 III 154, 3 IV 148.]