Pyrazoles
Pyrazoles are a group of heterocyclic chemical compounds . They have a five-membered ring with two neighboring nitrogen atoms and belong to the azoles . They are isomeric to the imidazoles and differ from the isothiazoles and isoxazoles by the formal replacement of a nitrogen atom with a sulfur or oxygen atom. 1 H -pyrazoles among the heteroaromatic , geminally substituted-3 H - or 4 H -pyrazoles are not aromatic . Formal hydrogenation of the double bonds gives pyrazolines and pyrazolidines in stages . The simplest representative of this group of substances is 1 H -pyrazole .
presentation
Pyrazoles can be prepared by a condensation reaction of a 1,3-di ketone with hydrazine .
1 H -pyrazoles are often in a prototropic equilibrium, as described in the reaction equation. The preference for one of the two forms is determined by the properties of the substituents. When designating these mixtures, the isomeric substituent position is put in brackets, e.g. B. 3 (5) -Methyl-5 (3) -phenyl-1 H -pyrazole.
properties
Pyrazoles have an aromatic character. They meet the Hückel criteria by using the free electron pair of the hydrogen- bearing nitrogen atom.
In principle, electrophilic substitutions are possible on them as aromatics . The extent to which these can be carried out on a specific compound depends on the substituents . Like all azoles, pyrazoles are also not stable to Lewis acids , so that Friedel-Crafts acylations, for example, cannot be carried out.
Substituents can be introduced on the nitrogen atom by deprotonating the nitrogen atom with a suitable base and then reacting the resulting anion with an electrophile . Haloalkanes or acyl halides , for example, can serve as electrophiles for this purpose. It produced N alkyls or N -Acyle.
Use of pyrazole derivatives
Industry
Pyrazole derivatives are used in a wide variety of industries, for example as optical brighteners ( blankophor ) for textiles, paper, detergents and plastics. Various dyes contain a pyrazole component ( pyrazolone blue , the azo dye tartrazine , indazole ). In addition, pyrazole derivatives can be used as complexing agents and extractants for metal ions .
Agrochemistry
In agriculture, pyrazole derivatives are used as herbicides ( azimsulfuron , halosulfuron ), acaricides ( fenpyroximate , tebufenpyrad ) and insecticides ( fipronil ). In addition, they have gained importance as nitrification inhibitors ( 3,4-dimethylpyrazole phosphate, DMPP), i.e. they serve as a non-washable nitrogen source.
medicine
Of great pharmaceutical importance are the pyrazolones , a group of analgesics which includes phenazone , aminophenazone , which has been taken out of the market , propyphenazone and metamizole . Related substances are the antirheumatic drugs phenylbutazone , oxyphenbutazone and sulfinpyrazone . The nonsteroidal anti-inflammatory drugs (NSAID) Lonazolac , Bufezolac and Trifezolac also have the pyrazole skeleton as their base, as does the COX-2 inhibitor celecoxib . Medicinal substances with a pyrazole base can also be found in a wide variety of areas: Betazole ( histamine agonist ), sulfaphenazole, sildenafil ( PDE-5 inhibitor ), zaleplon , cortivazole , granisetron ( antiemetic ), fomepizole , stanzolon , rimonabant . As estrogen receptor ligands are also tetrasubstituted pyrazoles in the conversation.
literature
- Houben-Weyl - Methods of Organic Chemistry , Volume E8b, Hetarene III, Part 2, p. 399, 4th edition, Georg Thieme Verlag.
- A. Schmidt, A. Dreger: Recent Advances in the Chemistry of Pyrazoles. Properties, Biological Activities, and Syntheses in Current Organic Chemistry15 (2011) 1423–1463, doi : 10.2174 / 138527211795378263 - Review articles on properties, biological activities and syntheses of pyrazoles.
- DT Davies: Basistexte Chemie: Aromatic Heterocyclen , 1st edition, pp. 28-34, Wiley-VCH, Weinheim 1995, ISBN 3-527-29289-6 .