Acetamidine hydrochloride

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.

Properties
Acetamidine hydrochloride is a hygroscopic solid which forms colourless monoclinic crystals. 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.


 * 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
Acetamidine hydrochloride is synthesised in a two-step process that begins with a solution of acetonitrile in ethanol at close to $0 degC$. First, the mixture is treated with anhydrous hydrogen chloride in a Pinner reaction, producing crystals of acetimido ethyl ether hydrochloride:


 * H3C\sC\tN + C2H5OH + HCl -> H3C\sC(\dNH*HCl)\sOC2H5

The imino ether salt is then treated with an excess of ammonia in dry ethanol, converting the ether to the amidine:


 * H3C\sC(\dNH*HCl)\sOC2H5 + NH3 -> H3C\sC(\dNH)\sNH2*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.

Applications
As 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, with acetaldehydes to form substituted imidazoles, and with imidates to form substituted triazines.

In particular, its reaction with a dicarbonyl intermediate is an early step in the synthesis of thyamine (vitamin B1) and many of its derivatives.