Imidazole

Structural formula
General
Surname	Imidazole
other names	1 H -imidazole ( IUPAC ) 1,3-diazole 1,3-diaza-2,4-cyclopentadiene Glyoxaline Imutex
Molecular formula	C 3 H 4 N 2
Brief description	colorless crystals, often light yellow due to contamination
External identifiers / databases
CAS number 288-32-4 EC number 206-019-2 ECHA InfoCard 100.005.473 PubChem 795 Wikidata Q328692
properties
Molar mass	68.08 g mol −1
Physical state	firmly
density	1.03 g cm −3
Melting point	90-91 ° C
boiling point	257 ° C
pK s value	6.95 (pK b , 25 ° C)
solubility	Easily soluble in water (633 g l −1 at 20 ° C), ethanol , chloroform , diethyl ether and pyridine
Refractive index	1.4801 (101 ° C)
safety instructions
GHS hazard labeling from  Regulation (EC) No. 1272/2008 (CLP) , expanded if necessary danger H and P phrases H: 360D-302-314 P: 201-280-301 + 330 + 331-305 + 351 + 338-308 + 310
Toxicological data	760 mg · kg -1 ( LD 50 ,  guinea pigs ,  oral ) 880 mg kg −1 ( LD 50 ,  mouse ,  oral ) 220 mg kg −1 ( LD 50 ,  rat ,  oral )
Thermodynamic properties
ΔH f 0	49.8 kJ / mol
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

Imidazole is a basic , organic compound from the group of five-membered, heterocyclic , aromatic amines . With two nitrogen atoms in the ring system, imidazole is the characteristic component in the side chain of the basic amino acid histidine .

Extraction and presentation

Heinrich Debus first produced imidazole in 1858 by reacting glyoxal ( ethanedial ) with ammonia NH ₃ , hence the outdated name glyoxaline .

In the Debus synthesis , suitably substituted 1,2- diketones , amines and aldehydes can be varied to produce appropriately substituted imidazoles.

More recently, other routes for the synthesis of imidazoles and benzimidazoles have been described.

Properties and toxicology

Imidazole forms colorless crystals that dissolve well in water. The heterocycle has both basic and acidic properties and is therefore an ampholyte . On warm-blooded animal acts imidazole with LD ₅₀ values between 220 (rat) and 880 mg / kg body weight (mouse) moderately toxic; in lower animals, as an antimetabolite of histidine and nicotinic acid, it has a significantly higher toxicity and is therefore used as a pesticide .

use

Imidazole is mainly used as a starting material for the manufacture of various drugs , especially fungicides of the azole type, e.g. B. Clotrimazole . It is also used to harden certain plastics .

Also using imidazole as buffer substance at the Karl Fischer titration for water determination. Eugen Scholz developed the pyridine-free Karl Fischer reagent with imidazole as the base in 1984. This reagent not only replaces the poisonous and malodorous pyridine , it also enables faster and more accurate titration , since imidazole buffers in a more favorable pH range than pyridine. Scholz's studies on stoichiometry also showed that methanol (solvent and at the same time involved in the reaction) can be replaced by other alcohols , e.g. B. ethanol , 2-propanol or methoxyethanol , which improved the titer stability of the reagent. Based on these findings, the following reaction equation for the Karl Fischer reaction resulted:

${\displaystyle \mathrm {\ ROH+SO_{2}+RN\longrightarrow (RNH)\cdot (SO_{3}R)} }$

${\displaystyle \mathrm {\ (RNH)\cdot (SO_{3}R)+I_{2}+H_{2}O+2\ RN\longrightarrow } \ }$ ${\displaystyle \mathrm {\ (RNH)\cdot (SO_{4}R)+2\ (RNH)\cdot I} }$

In the biochemistry imidazole is the elution of proteins used with a histidine tag (a plurality of consecutive histidines) are provided. The proteins are attached to a metal ion chelate matrix (IMAC) such as B. Ni ²⁺ - NTA bound and washed out of the column again by high concentrations of imidazole. Since imidazole also inhibits some alkaline phosphatases, it is a component of phosphatase inhibitor cocktails used in biochemistry.

Risk assessment

In 2012, imidazole was included in the EU's ongoing action plan ( CoRAP ) in accordance with Regulation (EC) No. 1907/2006 (REACH) as part of substance evaluation . The effects of the substance on human health and the environment are re-evaluated and, if necessary, follow-up measures are initiated. The reasons for the inclusion of imidazole were concerns about its classification as a CMR substance, high (aggregated) tonnage and widespread use. The reassessment took place from 2012 and was carried out by the United Kingdom . A final report was then published.

See also

• Pyrazole

Individual evidence

1. ↑ ^{a b c d e} Entry on imidazole. In: Römpp Online . Georg Thieme Verlag, accessed on June 20, 2014.
2. ↑ Entry on imidazole in the ChemIDplus database of the United States National Library of Medicine (NLM)
3. ↑ David R. Lide (Ed.): CRC Handbook of Chemistry and Physics . 90th edition. (Internet version: 2010), CRC Press / Taylor and Francis, Boca Raton, FL, Physical Constants of Organic Compounds, pp. 3-300.
4. ↑ ^{a b} Entry on imidazole in the GESTIS substance database of the IFA , accessed on January 10, 2017(JavaScript required) .
5. ↑ entry to imidazoles in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers and distributors harmonized classification and labeling may expand .
6. ↑ ^{a b c} Przeglad Epidemiologiczny. Vol. 67, p. 295, 1993.
7. ↑ ^{a b} German patent publication. Vol. # 3046325
8. ↑ David R. Lide (Ed.): CRC Handbook of Chemistry and Physics . 90th edition. (Internet version: 2010), CRC Press / Taylor and Francis, Boca Raton, FL, Standard Thermodynamic Properties of Chemical Substances, pp. 5-23.
9. ^ ^{A b} Albert Gossauer: Structure and Reactivity of Biomolecules , Verlag Helvetica Chimica Acta , 2006, ISBN 3-906390-29-2 , p. 483.
10. ↑ Imidazole Synthesis .
11. ↑ Claude Brunel, Guy Cathala: Imidazole: An inhibitor of l-phenylalanine-insensitive alkaline phosphatases of tissues other than intestine and placenta. In: Biochimica et Biophysica Acta (BBA) - Enzymology. 268, 1972, p. 415, doi : 10.1016 / 0005-2744 (72) 90337-3 .
12. ↑ Sigma Phosphatase Inhibitor Cocktail (PDF file)
13. ↑ European Chemicals Agency (ECHA): Substance Evaluation Conclusion and Evaluation Report .
14. ↑ Community rolling action plan ( CoRAP ) of the European Chemicals Agency (ECHA): Imidazole , accessed on May 20, 2019.