Pyrazole

From Wikipedia, the free encyclopedia
  (Redirected from Pechmann pyrazole synthesis)
Jump to: navigation, search
Pyrazole
Full structural formula
Skeletal formula with numbers
Ball-and-stick model
Space-filling model
Names
Preferred IUPAC name
1H-Pyrazole
Other names
1,2-Diazole
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
DrugBank
ECHA InfoCard 100.005.471
KEGG
Properties
C3H4N2
Molar mass 68.08 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
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
YesY verify (what is YesYN ?)
Infobox references

Pyrazole is an organic compound with the formula C3H3N2H. It is a heterocycle characterized by a 5-membered ring of three carbon atoms and two adjacent nitrogen atoms. Pyrazole is a weak base, with pKb 11.5 (pKa of the conjugated acid 2.49 at 25 °C).[1] Pyrazoles are also a class of compounds that have the ring C3N2 with adjacent nitrogen atoms.[2] Notable drugs containing a pyrazole ring are celecoxib (Celebrex) and the anabolic steroid stanozolol.

Preparation and reactions[edit]

Pyrazoles are synthesized by the reaction of α,β-unsaturated aldehydes with hydrazine and subsequent dehydrogenation:[3]

Pyrazoles synthesis.png

Substituted pyrazoles are prepared by condensation of 1,3-diketones with hydrazine. For example, acetylacetone and hydrazine gives 3,5-dimethylpyrazole:[4]

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

History[edit]

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

Conversion to scorpionates[edit]

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:

Potassium scorpionate.png

3,5-Diphenyl-1H-pyrazole[edit]

3,5-Diphenyl-1H-pyrazole is produced when (E)-1,3-diphenylprop-2-en-1-one is reacted with hydrazine hydrate in the presence of elemental sulfur[6] or sodium persulfate,[7] or by using a hydrazone in which case an azine is produced as a by-product.[8]

Scheme1jpg.jpg

Occurrence and uses[edit]

Celecoxib, a pyrazole derivative used as an analgesic

In 1959, the first natural pyrazole, 1-pyrazolyl-alanine, was isolated from seeds of watermelons.[9][10]

In medicine, derivatives of pyrazoles are used for their analgesic, antinociceptive, anti-inflammatory, antipyretic, antiarrhythmic, tranquilizing, muscle relaxing, analeptic, anticonvulsant, monoamineoxidase inhibiting, antidiabetic, antifungal, and antibacterial activities.[citation needed]

The pyrazole ring is found within a variety of pesticides as fungicides, insecticides and herbicides, including chlorfenapyr, fenpyroximate, fipronil, tebufenpyrad, tolfenpyrad, and tralopyril. [11]

Related heterocycles[edit]

Imidazole is an analog of pyrazole with two non-adjacent nitrogen atoms. In isoxazole, another analog, the nitrogen atom in position 1 replaced by oxygen.

References[edit]

  1. ^ Dissociation constants of organic acids and bases
  2. ^ Eicher, T.; Hauptmann, S. (2003). The Chemistry of Heterocycles: Structure, Reactions, Syntheses, and Applications (2nd ed.). Wiley-VCH. ISBN 3-527-30720-6. 
  3. ^ 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. 
  4. ^ Johnson, William S.; Highet, Robert J. (1963). "3,5-Dimethylpyrazole". Org. Synth. ; Coll. Vol., 4, p. 351 
  5. ^ 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. 
  6. ^ Outirite, Moha; Lebrini, Mounim; Lagrenée, Michel; Bentiss, Fouad (2008). "New one step synthesis of 3,5-disubstituted pyrazoles under microwave irradiation and classical heating". Journal of Heterocyclic Chemistry. 45 (2): 503–505. doi:10.1002/jhet.5570450231. 
  7. ^ Zhang, Ze; Tan, Ya-Jun; Wang, Chun-Shan; Wu, Hao-Hao (2014). "One-pot synthesis of 3,5-diphenyl-1H-pyrazoles from chalcones and hydrazine under mechanochemical ball milling". Heterocycles. 89 (1): 103–112. doi:10.3987/COM-13-12867. 
  8. ^ Lasri, Jamal; Ismail, Ali I. (2017, in press). "Metal-free and FeCl3-catalyzed synthesis of azines and 3,5-diphenyl-1H-pyrazole from hydrazones and/or ketones monitored by high resolution ESI+-MS". Indian Journal of Chemistry B.  Check date values in: |date= (help)
  9. ^ Fowden; Noe; Ridd; White (1959). Proc. Chem. Soc.: 131.  Missing or empty |title= (help)
  10. ^ 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. 
  11. ^ Chemical Class Pyrazole PAN Pesticides Database - Chemicals, retrieved 3 August 2017

Further reading[edit]

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.