Pyrazole is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

with the

formula In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwe ...

. It is a

heterocycle A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, proper ...

characterized as an

azole Azoles are a class of five-membered heterocyclic compounds containing a nitrogen atom and at least one other non-carbon atom (i.e. nitrogen, sulfur, or oxygen) as part of the ring. Their names originate from the Hantzsch–Widman nomenclature. Th ...

with a 5-membered ring of three

carbon Carbon () is a chemical element; it has chemical symbol, symbol C and atomic number 6. It is nonmetallic and tetravalence, tetravalent—meaning that its atoms are able to form up to four covalent bonds due to its valence shell exhibiting 4 ...

atoms and two adjacent nitrogen atoms, which are in ortho-substitution. Pyrazoles are also a class of compounds that have the ring C₃N₂ with adjacent nitrogen atoms. Pyrazole itself has few applications but many substituted pyrazoles are of commercial interest. Notable drugs containing a pyrazole ring are

celecoxib Celecoxib, sold under the brand name Celebrex among others, is a COX-2 inhibitor and nonsteroidal anti-inflammatory drug (NSAID). It is used to treat the pain and inflammation in osteoarthritis, acute pain in adults, rheumatoid arthritis, psor ...

(celebrex) and the anabolic steroid

stanozolol Stanozolol (Abbreviation, abbrev. Stz), sold under many brand names, is a synthetic androgen and anabolic steroid (AAS) medication derived from dihydrotestosterone (DHT). It is used to treat hereditary angioedema. It was developed by American ph ...

Properties

Pyrazole is a weak base, with p''K''_b 11.5 (p''K''_a of the conjugate acid 2.49 at 25 °C). According to

X-ray crystallography X-ray crystallography is the experimental science of determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to Diffraction, diffract in specific directions. By measuring th ...

, the compound is planar. The two C-N distances are similar, both near 1.33 Å

History

The term pyrazole was given to this class of compounds by German Chemist

Ludwig Knorr Ludwig Knorr (2 December 1859 – 4 June 1921) was a German chemist. Together with Carl Paal, he discovered the Paal–Knorr synthesis, and the Knorr quinoline synthesis and Knorr pyrrole synthesis are also named after him. The synthesis in 1883 ...

in 1883. In a classical method developed by German chemist Hans von Pechmann in 1898, pyrazole was synthesized from

acetylene Acetylene (Chemical nomenclature, systematic name: ethyne) is a chemical compound with the formula and structure . It is a hydrocarbon and the simplest alkyne. This colorless gas is widely used as a fuel and a chemical building block. It is u ...

and

diazomethane 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 ga ...

Preparation

Pyrazoles are synthesized by the reaction of α,β-unsaturated

aldehyde In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...

s with

hydrazine Hydrazine is an inorganic compound with the chemical formula . It is a simple pnictogen hydride, and is a colourless flammable liquid with an ammonia-like odour. Hydrazine is highly hazardous unless handled in solution as, for example, hydraz ...

and subsequent

dehydrogenation In chemistry, dehydrogenation is a chemical reaction that involves the removal of hydrogen, usually from an organic molecule. It is the reverse of hydrogenation. Dehydrogenation is important, both as a useful reaction and a serious problem. At ...

: :

Substituted pyrazoles are prepared by condensation of 1,3- diketones with hydrazine ( Knorr-type reactions). For example,

acetylacetone Acetylacetone is an organic compound with the chemical formula . It is classified as a 1,3-diketone. It exists in equilibrium with a tautomer . The mixture is a colorless liquid. These tautomers interconvert so rapidly under most conditions that ...

and

gives 3,5-dimethylpyrazole: :CH₃C(O)CH₂C(O)CH₃ + N₂H₄ → (CH₃)₂C₃HN₂H + 2 H₂O A wide variety of pyrazoles can be made so: : Aryl camphor-fused pyrazole synth

Occurrence and uses

In 1959, the first natural pyrazole, 1-pyrazolyl-alanine, was isolated from seeds of

watermelons The watermelon (''Citrullus lanatus'') is a species of flowering plant in the family Cucurbitaceae, that has a large, edible fruit. It is a scrambling and trailing vine-like plant, and is widely cultivated worldwide, with more than 1,000 ...

. In medicine, derivatives of pyrazole are widely used, including

and similar

COX-2 inhibitors Cyclooxygenase-2 inhibitors (COX-2 inhibitors), also known as coxibs, are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly target cyclooxygenase-2 ( COX-2), an enzyme responsible for inflammation and pain. Targeting selectivit ...

zaleplon Zaleplon, sold under the brand name Sonata among others, is a sedative and hypnotic which is used to treat insomnia. It is a nonbenzodiazepine or Z-drug of the pyrazolopyrimidine class. It was developed by King Pharmaceuticals and approved fo ...

, betazole, and CDPPB. The pyrazole ring is found within a variety of pesticides as fungicides, insecticides and herbicides, including fenpyroximate,

fipronil Fipronil is a broad-spectrum insecticide that belongs to the phenylpyrazole insecticide class. Fipronil disrupts the insect central nervous system by blocking the ligand-gated ion channel of the GABAA receptor ( IRAC group 2B) and glutamate-g ...

, tebufenpyrad and tolfenpyrad. Pyrazole moieties are listed among the highly used ring systems for small molecule drugs by the US FDA : Pyrazole SDHI intermediate

3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid is used in the manufacture of six commercial fungicides which are inhibitors of

succinate dehydrogenase Succinate dehydrogenase (SDH) or succinate-coenzyme Q reductase (SQR) or respiratory complex II is an enzyme complex, found in many bacterial cells and in the inner mitochondrial membrane of eukaryotes. It is the only enzyme that participates ...

. Pyrazole is an inhibitor of the

alcohol dehydrogenase Alcohol dehydrogenases (ADH) () are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to N ...

enzyme, and, as such, is used as an adjuvant with ethanol, to induce alcohol dependency in experimental laboratory mice.

Conversion to scorpionates

Pyrazoles react with potassium borohydride to form a class of ligands known as scorpionate. Pyrazole itself reacts with potassium borohydride at high temperatures (~200 °C) to form a

tridentate ligand A tridentate ligand (or terdentate ligand) is a ligand that has three atoms that can function as donor atoms in a coordination complex. Well-known tridentate ligands include diethylenetriamine with three nitrogen donor atoms, and the iminodiaceti ...

known as Tp ligand: : Potassium scorpionate

Properties

History

Preparation

Occurrence and uses

Conversion to scorpionates

See also

References

Further reading