Pyrazole

Pyrazole

Names
Preferred IUPAC name 1H-Pyrazole [1]
Systematic IUPAC name 1,2-Diazacyclopenta-2,4-diene
Other names 1,2-Diazole
Identifiers
CAS Number	288-13-1  Y
3D model (JSmol)	Interactive image
Beilstein Reference	103775
ChEBI	CHEBI:17241  Y
ChEMBL	ChEMBL15967  Y
ChemSpider	1019  Y
DrugBank	DB02757  Y
ECHA InfoCard	100.005.471
EC Number	206-017-1
Gmelin Reference	1360
KEGG	C00481  Y
PubChem CID	1048
UNII	3QD5KJZ7ZJ  Y
CompTox Dashboard (EPA)	DTXSID2059774
InChI InChI=1S/C3H4N2/c1-2-4-5-3-1/h1-3H,(H,4,5) Y Key: WTKZEGDFNFYCGP-UHFFFAOYSA-N Y InChI=1/C3H4N2/c1-2-4-5-3-1/h1-3H,(H,4,5) Key: WTKZEGDFNFYCGP-UHFFFAOYAW
SMILES c1cn[nH]c1
Properties
Chemical formula	C3H4N2
Molar mass	68.079 g·mol−1
Melting point	66 to 70 °C (151 to 158 °F; 339 to 343 K)
Boiling point	186 to 188 °C (367 to 370 °F; 459 to 461 K)
Basicity (pKb)	11.5
Hazards
GHS labelling: [2]
Pictograms
Signal word	Danger
Hazard statements	H302, H311, H315, H318, H319, H335, H372, H412
Precautionary statements	P260, P261, P262, P264, P264+P265, P270, P271, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P305+P354+P338, P316, P317, P319, P321, P330, P332+P317, P337+P317, P361+P364, P362+P364, P403+P233, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y  verify  (what is  YN ?) Infobox references

Pyrazole is an organic compound with the formula (CH)₃N₂H. It is a heterocycle characterized as an azole with a 5-membered ring of three carbon 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 (celebrex) and the anabolic steroid stanozolol.

Properties

Pyrazole is a weak base, with pK_b 11.5 (pK_a of the conjugate acid 2.49 at 25 °C). ^[3] According to X-ray crystallography, the compound is planar. The two C-N distances are similar, both near 1.33 Å ^[4]

History

The term pyrazole was given to this class of compounds by German Chemist Ludwig Knorr in 1883. ^[5] In a classical method developed by German chemist Hans von Pechmann in 1898, pyrazole was synthesized from acetylene and diazomethane. ^[6]

Preparation

Pyrazoles are synthesized by the reaction of α,β-unsaturated aldehydes with hydrazine and subsequent dehydrogenation: ^[7]

Substituted pyrazoles are prepared by condensation of 1,3-diketones with hydrazine (Knorr-type reactions). ^{[8] [9]} For example, acetylacetone and hydrazine gives 3,5-dimethylpyrazole: ^[10]

CH₃C(O)CH₂C(O)CH₃  +   N₂H₄  →   (CH₃)₂C₃HN₂H   +   2 H₂O

A wide variety of pyrazoles can be made so: ^[8]

Occurrence and uses

Celecoxib, a pyrazole-derived analgesic

In 1959, the first natural pyrazole, 1-pyrazolyl-alanine, was isolated from seeds of watermelons. ^{[11] [12]}

In medicine, derivatives of pyrazole are widely used, ^[13] including celecoxib and similar COX-2 inhibitors, zaleplon, betazole, and CDPPB. ^[14] The pyrazole ring is found within a variety of pesticides as fungicides, insecticides and herbicides, ^[13] including fenpyroximate, fipronil, tebufenpyrad and tolfenpyrad. ^[15] Pyrazole moieties are listed among the highly used ring systems for small molecule drugs by the US FDA ^[16]

3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid is used in the manufacture of six commercial fungicides which are inhibitors of succinate dehydrogenase. ^{[17] [18]}

Pyrazole is an inhibitor of the alcohol dehydrogenase enzyme, and, as such, is used as an adjuvant with ethanol, to induce alcohol dependency in experimental laboratory mice. ^[19]

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 known as Tp ligand:

See also

• 3,5-dimethylpyrazole
• Pyrazolidine, fully saturated analogue
• imidazole, structural analogue of pyrazole with two non-adjacent nitrogen atoms.
• isoxazole, another analogue, the nitrogen atom in position 1 replaced by oxygen.

References

1. "Front Matter". Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 141. doi:10.1039/9781849733069-FP001. ISBN   978-0-85404-182-4.
2. "Pyrazole". pubchem.ncbi.nlm.nih.gov. Retrieved 17 February 2024.
3. "Dissociation constants of organic acids and bases" (PDF). Archived (PDF) from the original on 12 July 2017.
4. La Cour, Troels; Rasmussen, Svend Erik; Hopf, Henning; Waisvisz, Jacques M.; Van Der Hoeven, Marcel G.; Swahn, Carl-Gunnar (1973). "The Structure of Pyrazole, C3H4N2, at 295 K and 108 K as determined by X-Ray Diffraction". Acta Chemica Scandinavica. 27: 1845–1854. doi:10.3891/acta.chem.scand.27-1845.
5. Knorr, L. (1883). "Action of ethyl acetoacetate on phenylhydrazine. I". Chemische Berichte. 16: 2597–2599. doi:10.1002/cber.188301602194.
6. von Pechmann, Hans (1898). "Pyrazol aus Acetylen und Diazomethan". Berichte der deutschen chemischen Gesellschaft (in German). 31 (3): 2950–2951. doi:10.1002/cber.18980310363.
7. Schmidt, Andreas; Dreger, Andrij (2011). "Recent Advances in the Chemistry of Pyrazoles. Properties, Biological Activities, and Syntheses". Curr. Org. Chem. 15 (9): 1423–1463. doi:10.2174/138527211795378263.
8. Nozari, Mohammad; Addison, Anthony W.; Reeves, Gordan T.; Zeller, Matthias; Jasinski, Jerry P.; Kaur, Manpreet; Gilbert, Jayakumar G.; Hamilton, Clifton R.; Popovitch, Jonathan M.; Wolf, Lawrence M.; Crist, Lindsay E.; Bastida, Natalia (2018). "New Pyrazole- and Benzimidazole-derived Ligand Systems". Journal of Heterocyclic Chemistry. 55 (6): 1291–1307. doi:10.1002/jhet.3155.
9. Eicher, T.; Hauptmann, S. (2003). The Chemistry of Heterocycles: Structure, Reactions, Syntheses, and Applications (2nd ed.). Wiley-VCH. ISBN   3-527-30720-6.
10. Johnson, William S.; Highet, Robert J. (1951). "3,5-Dimethylpyrazole". Organic Syntheses. 31: 43. doi:10.15227/orgsyn.031.0043.
11. Fowden; Noe; Ridd; White (1959). Proc. Chem. Soc. : 131.{{cite journal}}: Missing or empty |title= (help)
12. Noe, F. F.; Fowden, L.; Richmond, P. T. (1959). "alpha-Amino-beta-(pyrazolyl-N) propionic acid: a new amino-acid from Citrullus vulgaris (water melon)". Nature . 184 (4688): 69–70. Bibcode:1959Natur.184...69B. doi: 10.1038/184069a0 . PMID   13804343. S2CID   37499048.
13. Kabi, Arup K.; Sravani, Sattu; Gujjarappa, Raghuram; et al. (2022). "Overview on Biological Activities of Pyrazole Derivatives". Nanostructured Biomaterials. Materials Horizons: From Nature to Nanomaterials. pp. 229–306. doi:10.1007/978-981-16-8399-2_7. ISBN   978-981-16-8398-5.
14. Faria, Jéssica Venância; Vegi, Percilene Fazolin; Miguita, Ana Gabriella Carvalho; dos Santos, Maurício Silva; Boechat, Nubia; Bernardino, Alice Maria Rolim (1 November 2017). "Recently reported biological activities of pyrazole compounds". Bioorganic & Medicinal Chemistry. 25 (21): 5891–5903. doi:10.1016/j.bmc.2017.09.035. ISSN   0968-0896. PMID   28988624.
15. FAO
16. Taylor, R. D.; MacCoss, M.; Lawson, A. D. G. J Med Chem 2014, 57, 5845.
17. Walter, Harald (2016). "Fungicidal Succinate-Dehydrogenase-Inhibiting Carboxamides". In Lamberth, Clemens; Dinges, Jürgen (eds.). Bioactive Carboxylic Compound Classes: Pharmaceuticals and Agrochemicals. Wiley. pp. 405–425. doi:10.1002/9783527693931.ch31. ISBN   9783527339471.
18. Jeschke, Peter (2021). "Current Trends in the Design of Fluorine-Containing Agrochemicals". In Szabó, Kálmán; Selander, Nicklas (eds.). Organofluorine Chemistry. Wiley. pp. 363–395. doi:10.1002/9783527825158.ch11. ISBN   9783527347117. S2CID   234149806.
19. Xiao, T.; Chen, Y.; Boisvert, A.; Cole, M.; Kimbrough, A. (2023). "Chronic Intermittent Ethanol Vapor Exposure Paired with Two-Bottle Choice to Model Alcohol Use Disorder". Journal of Visualized Experiments (196). doi:10.3791/65320. PMC   11164185 . PMID   37427930.

Further reading

A. Schmidt; A. Dreger (2011). "Recent Advances in the Chemistry of Pyrazoles. Part 2. Reactions and N-Heterocyclic Carbenes of Pyrazole". Curr. Org. Chem. 15 (16): 2897–2970. doi:10.2174/138527211796378497.