Acetamidine hydrochloride is an organic compound with the formula CH3C(NH)NH2·HCl, used in the synthesis of many nitrogen-bearing compounds. It is the hydrochloride of acetamidine, one of the simplest amidines.
| Names | |
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| IUPAC name
Ethanimidamide;hydrochloride
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| Other names
Acetamidinium chloride
Ethanimidamide monohydrochloride | |
| Identifiers | |
3D model (JSmol)
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| ChemSpider | |
| ECHA InfoCard | 100.004.274 |
| EC Number |
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PubChem CID
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| UNII | |
CompTox Dashboard (EPA)
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| Properties | |
| C2H7ClN2 | |
| Molar mass | 94.54 g·mol−1 |
| Structure | |
| Monoclinic | |
| C2/c | |
a = 11.673, b = 9.862, c = 9.601 α = 90°, β = 111.71°, γ = 90°[1]
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| Hazards[2] | |
| GHS labelling: | |
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| Warning | |
| H315, H319, H335 | |
| P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P362+P364, P403+P233, P501 | |
| NFPA 704 (fire diamond) | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Properties
editAcetamidine hydrochloride is a hygroscopic solid which forms colourless monoclinic crystals.[1] It is soluble in water and alcohol.
It releases ammonium chloride upon heating. Dry acetamidine hydrochloride releases acetonitrile, while in aqueous solution, it instead undergoes hydrolysis to acetic acid and ammonia.[3]
- CH3C(NH)NH2·HCl → CH3CN + NH4Cl
- CH3C(NH)NH2·HCl + 2 H2O → CH3COOH + NH3 + NH4Cl
As free base amidines are strong Lewis bases, acetamidine hydrochloride is a weak Lewis acid. Treatment with strong base gives free base acetamidine:
- CH3C(NH)NH2·HCl + KOH → CH3C(NH)NH2 + KCl + H2O
Synthesis
editAcetamidine hydrochloride is synthesised in a two-step process that begins with a solution of acetonitrile in ethanol at close to 0 °C.[4] First, the mixture is treated with anhydrous hydrogen chloride in a Pinner reaction, producing crystals of acetimido ethyl ether hydrochloride:
- H3C−C≡N + C2H5OH + HCl → H3C−C(=NH·HCl)−OC2H5
The imino ether salt is then treated with an excess of ammonia in dry ethanol, converting the ether to the amidine:
- H3C−C(=NH·HCl)−OC2H5 + NH3 → H3C−C(=NH)−NH2·HCl + C2H5OH
All reagents must be thoroughly dried using a strong desiccant such as phosphorus pentoxide, as the intermediate imido ether is susceptible to hydrolysis, yielding ammonium chloride and ethyl formate. Layers of ammonium chloride can form on the imido ether salt, limiting the formation of amidine.[4]
Applications
editAs a source of amidine, acetamidine hydrochloride is a precursor to the industrial and laboratory synthesis of many nitrogen compounds. It reacts with β-dicarbonyls to produce substituted pyrimidines,[5] with acetaldehydes to form substituted imidazoles,[6] and with imidates to form substituted triazines.[7]
In particular, its reaction with a dicarbonyl intermediate is an early step in the synthesis of thyamine (vitamin B1) and many of its derivatives.[8]
References
edit- ^ a b Cannon, Jack R.; White, Allan H.; Willis, Anthony C. (1976). "Crystal structure of acetamidinium chloride". Journal of the Chemical Society, Perkin Transactions 2 (3): 271. doi:10.1039/P29760000271.
- ^ Fisher Scientific, acetamidine hydrochloride 98+%
- ^ Shriner, R. L.; Neumann, Fred W. (1944). "The Chemistry of the Amidines". Chemical Reviews. 35 (3): 351–425. doi:10.1021/cr60112a002.
- ^ a b Dox, A. W. (1928). "Acetamidine hydrochloride". Organic Syntheses. doi:10.15227/orgsyn.008.0001.
- ^ Chu, Xue-Qiang; Cao, Wen-Bin; Xu, Xiao-Ping; Ji, Shun-Jun (2017). "Iron Catalysis for Modular Pyrimidine Synthesis through β-Ammoniation/Cyclization of Saturated Carbonyl Compounds with Amidines". The Journal of Organic Chemistry. 82 (2): 1145–1154. doi:10.1021/acs.joc.6b02767.
- ^ Wang, Jing; Zhang, Fang-Dong; Tang, Dong; Wu, Ping; Zhang, Xue-Guo; Chen, Bao-Hua (2017). "I2/TBPB mediated oxidative reaction of aryl acetaldehydes with amidines: Synthesis of 1,2,5-triaryl-1H-imidazoles". RSC Advances. 7 (40): 24594–24597. Bibcode:2017RSCAd...724594W. doi:10.1039/C7RA01966A.
- ^ US patent 3203550A, Frederic Charles Schaefer, "Method for the preparation of substituted s-triazine compounds", issued 1965-08-31, assigned to American Cyanamid Company
- ^ Tylicki, Adam; Łotowski, Zenon; Siemieniuk, Magdalena; Ratkiewicz, Artur (2018). "Thiamine and selected thiamine antivitamins — biological activity and methods of synthesis". Bioscience Reports. 38. doi:10.1042/BSR20171148. PMID 29208764.