Guanidine

Key takeaways

Guanidine belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Guanidine to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Guanidine from memory before moving on to harder problems.

Reference excerpt

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. A guanidine moiety also appears in larger organic molecules, including on the side chain of arginine.

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 NH2 group. A detailed crystallographic analysis of guanidine was elucidated 148 years after its first synthesis, despite the simplicity of the molecule. In 2013, the positions of the hydrogen atoms and their displacement parameters were accurately determined using single-crystal neutron diffraction.

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. 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. Isothiouronium salts (S-alkylated thioureas) react with amines to give guanidinium salts:

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 Bernhard Rathke.

Chemistry

Guanidinium cation The conjugate acid is called the guanidinium cation, (C(NH2)+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 pKa is 13.6 (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 Guanidine can be selectively detected using sodium 1,2-naphthoquinone-4-sulfonic acid (Folin's reagent) and acidified urea.

Uses

Industry The main salt of commercial interest is the nitrate [C(NH2)3]NO3. 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. Guanidinium chloride 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.

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. 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.

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

Guanidine derivatives

Guanidines are a group of organic compounds sharing a common functional group with the general structure (R1R2N)(R3R4N)C=N−R5. 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. One technique for persubstituted guanidine synthesis converts a urea to the diaminodichloride with phosgene and then uses the product to alkylate another amine. Galegine is an isoamylene guanidine.

See also Sakaguchi test Y-aromaticity Amidine

References

Illustrations

Worked examples

Example 1 — a first encounter with Guanidine

Start with the simplest possible case. Write down what Guanidine claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Guanidine before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Guanidine ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Guanidine

In research: Guanidine appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Guanidine in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Guanidine is common in secondary-school and first-year university syllabi. It links to neighbouring topics Bases (chemistry), Guanidines, Organic compounds with 1 carbon atom, so understanding it makes those chapters shorter.
In everyday life: Look for Guanidine outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Guanidine in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Guanidine means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Guanidine out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Guanidine in simple terms?

Guanidine is the compound with the formula HNC(NH2)2. It is a colourless solid that dissolves in polar solvents.

Why does Guanidine matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Guanidine?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Guanidine.