Azine Explained

Azine should not be confused with azene.

Azines are a functional class of organic compounds with the connectivity RR'C=N-N=CRR'. These compounds are the product of the condensation of hydrazine with ketones and aldehydes, although in practice they are often made by alternative routes. Ketazines are azines derived from ketones. For example, acetone azine is the simplest ketazine. Aldazines are azines derived from aldehydes.

Preparation

The usual method of industrial production is the peroxide process, starting from the ketone, ammonia, and hydrogen peroxide.

In the laboratory, azines are typically prepared by condensation of hydrazine with two equivalents of a carbonyl.

Azines are also produced when chalcone reacts with a hydrazone to produce 3,5-diphenyl-1H-pyrazole,^[1] in a conversion also carried out with hydrazine hydrate.^{[2] [3]}

Reactions

Azines characteristically undergo hydrolysis to hydrazines. The reaction proceeds by the intermediacy of a hydrazone:

R₂C=N-N=CR₂ + H₂O → R₂C=N-NH₂ + R₂C=O

R₂C=N-NH₂ + H₂O → N₂H₄ + R₂C=O

Azines have been used as precursors to hydrazones:^[4]

R₂C=N-N=CR₂ + N₂H₄ → 2 R₂C=N-NH₂

They are also precursors to diazo compounds.^{[5] [4] [6]}

The coordination chemistry of azines (as ligands) has also been studied.^{[7] [8] [9]}

Acetone is used to derivatize hydrazine into acetone azine for analysis by gas chromatography. This method is used to determine trace levels of hydrazine in drinking water^[10] and pharmaceuticals.^[11]

Applications

Ketazines are also important intermediates in the industrial production of hydrazine hydrate by the peroxide process.^[12] In the presence of an oxidant, ammonia and ketones react to give hydrazine via ketazine:

2 Me(Et)C=O + 2 NH₃ + H₂O₂ → Me(Et)C=NN=C(Et)Me + 2 H₂OThe ketazine can be hydrolyzed to the hydrazine and regenerate the ketone:

Me(Et)C=NN=C(Et)Me + 2 H₂O → 2 Me(Et)C=O + N₂H₄

Ketazines have been also used as sources of hydrazine produced in situ, for example in the production of herbicide precursor 1,2,4-triazole.^[13]

Further reading

• E. C. . Gilbert . Studies on Hydrazine. The Hydrolysis of Dimethylketazine and the Equilibrium between Hydrazine and Acetone . . 1929 . 51 . 11 . 3394–3409 . 10.1021/ja01386a032.
• Eichenhofer . Kurt-Wilhelm . Schliebs . Reinhard . . Production of ketazines . US . 3965097 . 1976-06-22. .
• Jean-Pierre . Schirmann . Jean . Combroux . Serge Yvon . Delavarenne . Produits Chimiques Ugine Kuhlmann . US . 3972878 . Method for preparing azines and hydrazones . 1976-08-03. .
• Jean-Pierre . Schirmann . Pierre . Tellier . Henri . Mathais . Francis . Weiss . Produits Chimiques Ugine Kuhlmann . US . 3978049 . Process for the preparation of hydrazine compounds . 1976-08-31. .
• Jean-Pierre . Schirmann . Jean . Combroux . Serge Yvon . Delavarenne . Produits Chimiques Ugine Kuhlmann . US . 4093656 . Method for making azines . 1978-06-06. .
• Jean-Pierre . Schirmann . Jean . Combroux . Serge Y. . Delavarenne . . US . 4724133 . Preparation of a concentrated aqueous solution of hydrazine hydrate . 1988-02-09. .

Notes and References

1. 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. 2018. Indian Journal of Chemistry, Section B. 57B. 3. 362–373. Jamal. Lasri. Ali I.. Ismail.
2. New one step synthesis of 3,5-disubstituted pyrazoles under microwave irradiation and classical heating. 2008. Journal of Heterocyclic Chemistry. 45. 2. 503–505. 10.1002/jhet.5570450231. Moha. Outirite. Mounim. Lebrini. Michel. Lagrenée. Fouad. Bentiss.
3. One-pot synthesis of 3,5-diphenyl-1H-pyrazoles from chalcones and hydrazine under mechanochemical ball milling. 2014. Heterocycles. 89. 1. 103–112. 10.3987/COM-13-12867. Ze. Zhang. Ya-Jun. Tan. Chun-Shan. Wang. Hao-Hao. Wu. 2024-02-17 . free.
4. Staudinger. H.. Hermann Staudinger. Gaule. Alice. Vergleich der Stickstoff-Abspaltung bei verschiedenen aliphatischen Diazoverbindungen. Berichte der Deutschen Chemischen Gesellschaft. July 1916. 49. 2. 1897–1918. 10.1002/cber.19160490245.
5. Day. A. C.. Raymond. P.. Southam. R. M.. Whiting. M. C.. The preparation of secondary aliphatic diazo-compounds from hydrazones. Journal of the Chemical Society C: Organic. 1966. 467. 10.1039/J39660000467.
6. .
7. Gudkova. A. S.. Reutov. O. A.. Aleinikova. M. Ya.. Reactions of hydrazones and azines with metal salts. Bulletin of the Academy of Sciences of the USSR Division of Chemical Science. August 1962. 11. 8. 1298–1302. 10.1007/BF00907973.
8. Gudkova. A. S.. Aleinikova. M. Ya.. Reutov. O. A.. Reactions of hydrazones and azines with metal salts Communication 5. Reactions of hydrazones and azines with mercuric halides. Bulletin of the Academy of Sciences, USSR Division of Chemical Science. May 1966. 15. 5. 807–811. 10.1007/BF00849376.
9. King. Fiona. Nicholls. David. Complex of titanium halides with acetone azine and its isomer 3, 5, 5-trimethyl-pyrazoline. Inorganica Chimica Acta. January 1978. 28. 55–58. 10.1016/S0020-1693(00)87413-7.
10. Davis, II. William E.. Li. Yongtao. Analysis of Hydrazine in Drinking Water by Isotope Dilution Gas Chromatography/Tandem Mass Spectrometry with Derivatization and Liquid−Liquid Extraction. Analytical Chemistry. July 2008. 80. 14. 5449–5453. 10.1021/ac702536d. 18564853.
11. Sun. Mingjiang. Bai. Lin. Liu. David Q.. A generic approach for the determination of trace hydrazine in drug substances using in situ derivatization-headspace GC–MS. Journal of Pharmaceutical and Biomedical Analysis. February 2009. 49. 2. 529–533. 10.1016/j.jpba.2008.11.009. 19097722.
12. Jean-Pierre Schirmann, Paul Bourdauducq "Hydrazine" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2002. .
13. Nagata . Nobuhiro . Nishizawa . Chiharu . Kurai . Toshikiyo . Mitsubishi Gas Chemical Co. . Method of producing 1,2,4-triazole . US . 6002015 . 1999-12-14. .