PYRIDINE: STRUCTURE, PROPERTIES, USES, TOXICITY, SYNTHESIS - CHEMISTRY - 2025

The pyridine is an aromatic amine having the chemical formula C ₅ H ₅ N is the version of nitrogenous benzene, as a -CH has been replaced by a nitrogen atom (N). Together with pyrrole, pyridine makes up the group of the simplest aromatic amines of all.

Pyridine was initially produced from coal tar, but it was a low yield method. This led to the creation of several methods for its chemical synthesis, prevailing that in which the reaction of formaldehyde, acetaldehyde and ammonia is used.

Structural formula of pyridine. Source: Calvero. / Public domain

Pyridine was first obtained by Thomas Anderson (1843), a Scottish chemist, who by heating animal meat and bones produced an oil from which pyridine was purified.

Thomas Anderson (July 1819)

Pyridine is used as a raw material for the synthesis of compounds that eliminate and control the proliferation of insects, fungi, herbs, etc. It is also used in the manufacture of numerous medicines and vitamins, as well as being used as a solvent.

Pyridine is a toxic compound that can chronically damage the liver, kidneys, and central nervous system function. Pyridine can enter the body by ingestion, inhalation, and diffusion through the skin. It is known in the chemical field for being a substance capable of causing impotence in men.

Structure of pyridine

Molecular

Molecular structure of pyridine. Source: Benjah-bmm27 / Public domain

The upper image shows the molecular structure of pyridine represented by a spheres and bars model. As can be seen, its molecule is very similar to that of benzene, with the only difference that it has one of its carbons (black spheres) replaced by nitrogen (blue sphere).

Nitrogen, being more electronegative, attracts electron density towards itself, which creates a permanent dipole moment in pyridine. Therefore, pyridine molecules interact through dipole-dipole forces.

Hydrogen atoms are the electron-poor regions, so they will be oriented in the direction of the nitrogen atom of a neighboring molecule.

Crystalline

Crystal structure of pyridine. Source: Orci / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0)

Pyridine molecules have not only the dipole-dipole forces, but also the interactions of the aromatic rings. Thus, these molecules manage to position themselves in an orderly manner to produce a crystal with an orthorhombic structure (upper image) at a temperature of -41.6 ° C.

Pyridine Properties

Pyridine sample. LHcheM / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0)

Physical appearance

Colorless liquid with a pungent odor, similar to fish.

Molar mass

79.1 g / mol

Density

0.9819 g / mL

Melting point

-41.6 ºC

Boiling point

115.2 ºC

Solubility

It is miscible with water, and also with alcohol, ether, petroleum ether, oils and many organic liquids in general.

Vapor pressure

16 mmHg at 20 ° C.

Vapor density

2.72 relative to water = 1

Refractive index (n

1,5093

Viscosity

0.88 cP

Dipole moment

2.2 D

ignition point

21 ºC

Auto-ignition temperature

482 ºC

Decomposition

When heated to decomposition it emits cyanide smoke.

Corrosion

Pyridine in liquid form attacks some forms of plastics, rubbers, and coatings.

pH

8.5 (0.2 M solution in water)

Basicity and reactivity

Pyridine is a weak base. It is a tertiary amine whose 0.2 M solution in water produces a pH of 8.5. It has low affinity for electrons due to the electronegativity of nitrogen, so its carbons do not usually undergo electrophilic substitution.

Pyridine undergoes nucleophilic substitution, preferably at the C ₄ and C _{2 positions} of the ring. Due to its ability to donate electrons, pyridine is more resistant to oxidation than benzene and reacts violently with sulfuric acid, nitric acid, and maleic anhydride.

Uses of pyridine

Pesticides

Pyridine is a precursor to the herbicides Paraquat and Diquat. In the same way, it is used for the synthesis of the insecticide Chlorpyrifos, whose initial step is the chlorination of pyridine. It is also the initial raw material for obtaining the fungicide based on pyrithione.

Solvent

Pyridine is a polar solvent, used for dehalogenation reactions and the extraction of antibiotics. Pyridine is used as a solvent in the paint and rubber industries, and also in research laboratories as a solvent in the extraction of plant hormones.

Medicine

Pyridine serves as the starting point in the synthesis of cetylpyridinium and laurylpyridinium, compounds that are used as antiseptics in oral and dental care products. The pyridine molecule is part of the chemical structure of many drugs.

For example, esmeprazole, used to treat gastroesophageal reflux. Loratidine is another medicine prepared based on pyridine, known by the name of Claritin, which is used as a treatment for allergic processes.

Pyridine tablets (phenazopyridine) are used in the symptomatic treatment of an irritation of the urinary tract, which is accompanied, in some cases, by pain, burning and the urge to urinate. Phenazopyridine is a dye that acts as an analgesic in the urinary tract.

Diacylhydrazine is a derivative of pyridine that has an antibacterial activity that exerts on gram negative bacteria, such as E. coli, and gram positive bacteria, such as S. albus.

Pyridine serves as the basis for thiazolo pyridine, a compound with antiviral activity, especially against the influenza β-Mass virus. 2-Acetylpyridine, a derivative of pyridine, has great antitumor activity and is an inhibitor of leukemia.

Others

Pyridine is used in the manufacture of vitamins, rubber products, adhesives, paints, and insecticides. It is also used in the denaturation of alcohol and in the dyeing of some textiles.

20% of pyridine is used in the preparation of piperidine. Piperidine is involved in vulcanization and agriculture.

Pyridine is also used in the synthesis of polycarbonate resins, as a food flavoring and as a reagent for the detection of cyanide.

Toxicity

- Pyridine enters the body mainly by inhalation and diffusion through the skin. Acute exposure to pyridine can cause eye and skin irritation and burns on contact.

- Pyridine can cause dermatitis and allergies on the skin. The development of allergy may be accompanied in addition to itching and a rash.

- Inhalation of pyridine can cause irritation of the nose and throat, accompanied by coughing and wheezing asthmatic breathing.

- By ingestion, pyridine can cause nausea, vomiting, diarrhea and abdominal pain. Likewise, incorporating a high dose of pyridine into the body can cause: headache, fatigue, fainting, lightheadedness, dizziness, confusion, and eventually coma and death.

- The organs most affected by the action of pyridine are the liver, kidneys, male genitalia and the central nervous system. It can also act on the bone marrow, inducing the production of blood platelets. A carcinogenic action of pyridine has not been evidenced in animal experiments.

OSHA set an airborne exposure limit of 5 ppm per 8-hour work shift.

Synthesis

The first methods of obtaining pyridine were based on its extraction from organic materials. Thomas Anderson (1843) first obtained pyridine by heating animal meat and bones. In a first stage, Anderson produced an oil from which he managed to distill the pyridine.

Traditionally, pyridine was obtained from coal tar or from the gasification of coal. These procedures were cumbersome and of little yield, since the pyridine concentration in these raw materials was very low. So a method of synthesis was needed.

Chichibabin method

Although there are many methods for the synthesis of pyridine, the Chichibabin procedure introduced in 1923 is still mainly used. In this method pyridine is synthesized from the reaction of formaldehyde, acetaldehyde and ammonia, which are cheap reagents.

In the first stage, formaldehyde and acetaldehyde react to form the acrolein compound, in a Knoevenagel condensation reaction, also forming water.

Pyridine condensation from acrolein and acetaldehyde

Finally, in a second stage, acrolein reacts with formaldehyde and ammonia to form dihydropyridine. Subsequently, the dihydropyridine is oxidized to pyridine in a reaction at 350-550 ° C in the presence of a solid catalyst, for example, silica-alumina.

Reactions

Electrophilic substitutions

These substitutions do not usually occur due to the low electron density of pyridine.

Sulfanation is more difficult than nitration. But bromination and chlorination occur more easily.

Pyridine-N-oxide

The site of oxidation in pyridine is the nitrogen atom, the oxidation being produced by peracids (acids that have an OOH group). Nitrogen oxidation promotes electrophilic substitution at carbons 2 and 4 of pyridine.

Nucleophilic substitutions

Pyridine can undergo various nucleophilic substitutions due to the low electron density of the pyridine ring carbons. These substitutions occur more easily in the pyridine molecule modified by bromine, chlorine, fluorine, or sulfonic acid.

The compounds that carry out the nucleophilic attacks on pyridine are usually: alkoxides, thiolates, amines and ammonia.

Radical reactions

Pyridine can be dimerized by radical reactions. The radical dimerization of pyridine is carried out with elemental sodium or Raney nickel, being able to produce 4,4'-biperidine or 2,2'-biperidine.

Reaction on the nitrogen atom

Acids, according to Lewis, easily add to the nitrogen atom of pyridine, forming pyridinium salts. Pyridine is a Lewis base that donates a pair of electrons.

Hydrogenation and reduction reaction

Piperidine is produced by hydrogenating pyridine with nickel, cobalt, or ruthenium. This reaction is carried out at high temperatures accompanied by the use of a catalyst.

References

1. Graham Solomons TW, Craig B. Fryhle. (2011). Organic Chemistry. (10 ^th edition.). Wiley Plus.
2. Carey F. (2008). Organic Chemistry. (Sixth edition). Mc Graw Hill.
3. Morrison and Boyd. (1987). Organic chemistry. (Fifth edition). Addison-Wesley Iberoamericana.
4. Wikipedia. (2020). Pyridine. Recovered from: en.wikipedia.org
5. National Center for Biotechnology Information. (2020). Pyridine. PubChem Database., CID = 1049. Recovered from: pubchem.ncbi.nlm.nih.gov
6. Laura Foist. (2020). Pyridine: Structure, Formula & Physical Properties. Study. Recovered from: study.com
7. Ataf Ali Altaf, Adnan Shahzad, Zarif Gul, Nasir Rasool, Amin Badshah, Bhajan Lal, Ezzat Khan. (2015). A Review on the Medicinal Importance of Pyridine Derivatives. Journal of Drug Design and Medicinal Chemistry. Vol. 1, No. 1, pp. 1-11. doi: 10.11648 / j.jddmc.20150101.11
8. WebMD. (2020). Pyridin Tablet. Recovered from: webmd.com
9. New Jersey Department of Health and Senior Services. (2002). Pyridine.. Recovered from: nj.gov