Amidines from imidic esters

As in 10-55 hydrazides and hydroxamic acids can be prepared from carboxylic esters, with hydrazine and hydroxylamine, respectively. Both hydrazine and hydroxylamine react more rapidly than ammonia or primary amines (the alpha effect, p. 445). Imidates, RC(=NH)OR, give amidines, RC(=NH)NH2. Lactones, when treated with ammonia or primary amines, give lactams. Lactams are also produced from y- and 5-amino esters in an internal example of this reaction. 

Amidines of aliphatic acids are generally not reducible in buffered solution. Some amidines derived from aromatic acids are reducible at very negative potentials and only in a narrow pH interval from slightly acid to alkaline solution. The reduction is similar to that of imidic esters [Eq. (10)], and yields the amine [44]. 

Acylation of nitrogen compounds by imidic esters. It was mentioned above that synthesis of amidines from orthoesters proceeds through imidic esters, so that both classes of compound are normally treated together in reviews.819-821 Accordingly, also, it is, of course, possible to use imidic ester hydrochlorides as usually prepared from nitriles and to treat these with ammonia or amines.820 Care must be taken, however, with primary amines lest the imido group be also exchanged for the residue from the amine, particularly at higher temperatures ... 

An approximately 10 % solution or suspension of 0.1 mole of an imidic ester hydrochloride in anhydrous ethanol containing 0.13 mole of ammonia is shaken in a closed vessel for 2 to 3 days at room temperature. The precipitated ammonium chloride is filtered off, the filtrate is diluted with ether, and the precipitated amidine hydrochloride is collected and recrystallized from ethyl methyl ketone and alcohol. 

Abb. 7.14. Imidic acid ester hydrochlorides (F)—to be prepared from nitriles, hydrogen chloride (gas) and methanol acc. to Fig. 7.13—, their trans-formability into orthoester (A) or amidine (I) and the corresponding reaction mechanisms. 

The aldehyde (5) can be made in high yield from the amidine (6) via the unisolated 2-dichloromethylimidazole (Scheme 2.2.3). Dichloroacetonitrile is converted into its imidate with methanolic sodium methoxide, and then into the amidine with aminoacetaldehyde dimcthylacetal. When (6) is heated in formic acid it is converted almost quantitatively into the 2-carbaldehyde the use of trifluoroacctic acid at reflux gives around 60% of (5). Using essentially the same method, imidazole-2-carboxylic acid and its ethyl ester can also be made veiy efficiently when trichloroacctonitrilc and the acetal arc used to prepare the amidine [16],... 

Since the discovery of the synthesis of 1,3,5-triazine-2,4-diamines from biguanide and its derivatives,328-329 a large variety of carboxylic acid derivatives, e.g. acid chlorides,332 342,346 lactones,333 amides,334,335 imides,336,337 ortho esters,338 amidines,338 esters334, 339- 343 and acid anhydrides,332,344,345 have been used as starting materials in the preparation of these triazines (Table 8).330,331 The preferred procedure is the reaction of biguanides 1 with esters 2 in alcoholic solution, sometimes in the presence of a basic catalyst. The reaction mechanism is thought to be as indicated.341... 

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