Amidines phosphorylated

The third step is hydrolysis of the N-phosphorylated amidines which is carried out by either acid or alkali depending on the substrate. 

The first dibenz[/>,e]azepine 23 was prepared by cyclization of amidine 22 with phosphoryl chloride in refluxing nitrobenzene.103... 

Azines have been prepared by initial condensation of diethoxyphosphinyIhydrazine anions with aldehydes or ketones (Scheme 9). Phosphoryl azides undergo 1,3-dipolar cycloaddition to 2-tetralone enamines to give triazolines, possibly en route to amidines. A full paper on the addition of diethyl dibromophosphoramidate to alkenes(leading to the synthesis of 2-bromoalkylamines) has appeared. ... 

Other vinylphosphonates, e.g. (148), undergo reactions with hydrazines, hydroxyl-amines, or amidines to yield C-phosphorylated 1,2-diazoles, 1,2-oxazoles, or 1,3-... 

Several variations of this synthetic route have been developed. For example, condensation of the methyltriazole (21) with thiourea gives the thiol derivative (22), and reaction with phosphoryl chloride in dimethylformamide converts the amino-amide to a cyano-amidine, which can be reduced to the 4-amino-5-aminomethyl derivative (Scheme 47). ... 

Cusack el al,86 have synthesized 5-aminoimidazoles by ring closure of formylglycine amidines (11) induced by heating or with phosphoryl chloride. 

Ring closure of formylglycine amidines, induced by heating alone or in the presence of phosphoryl chloride, bears similarities to the general method... 

If DAMN is mono-N-alkylated before reaction with the carbonyl reagent the method gives 1-alkylimidazoles [15]. For example, 4,5-dicyano-l-(2, 3, 5 -tri-0-benzoyl-)S-D-ribofuranosyl)imidazole (57%) has been made by treatment of the ribosylamino-DAMN with triethyl orthoformate at 90°C in anisole under nitrogen for 5h. The intermediate enamine is not isolated in this case [42]. When DAMN is treated with AyV-dialkylamides in the presence of phosphoryl chloride, the Schiff base (14) (R = NR R ) cyclizes to give 2-dialkylaminoimidazoles (15) (R = NR R ), including 4,5-dicyanoimidazole (15) (R = H) when DMF is used [15], Imidazoles (15) (R = OR, NR R ) can be made in one step when DAMN reacts with orthoesters or iminoether hydrochlorides. Under mild reaction conditions the intermediate alkoxyimines (14) (R = OR" ) or amidines (14) (R = NR R ) can be isolated before oxidation to (15) [46, 47, 49], Table 2.1.4 lists some examples. 

Another reaction which proceeds through an intermediate amidine is that in which 4-foimylimidazoles are made from 5-aminopyrimidine and an N-substituted imidoyl chloride in the presence of phosphoryl chloride. Once the intermediate amidine has formed, the pyrimidine ring opens up. Yields, however, are rather low ( 25%) [45]. 

The inner amide group is activated by phosphorylation and then converted into an amidine by the addition of ammonia derived from glutamine,... 

Amidine synthesis. Alkynes, amines, and suUbnylazides (or phosphoryl azides) are combined to generate amidines. The alkynes and/or the amines can he functionahzed, and their use leads to amidines containing an a-amino group or a phosphoranylalkyl group, when starting from ynamides and imidophosphoranes, respectively. 

In the still more 7t-deficient 1,2,3-triazole series (see 20), several 4-amino-5-formyl derivatives resisted both direct acylation and acetal formation. A successful alternative was to form intermediates with side chains conjugated to the nucleus. For example, 1- and 2-methyl-, as well as 3-benzyl-4-amino-l,2,3-triazole-5-aldehydes reacted with a cold mixture of dimethylformamide and phosphoryl chloride to give excellent yields of, e.g., 3-benzyl-4-dimethyl-aminomethyleneamino-l,2,3-triazole-5-aldehyde (84). This was converted to 9-benzyl-8-azapurine (see 21) in excellent yield by refluxing in methanolic ammonium acetate.87 In a variation of this reaction, an imidate (85) replaced the amidine (84) as intermediate. Thus, 4-amino-l-methyl-l,2,3-triazole-5-aldehyde and triethyl orthoacetate, refluxed for 2 hr, gave an excellent yield of 4-ethoxyethylideneamino-l,2,3-triazole-5-aldehyde (85), cyclized, by stirring in cold ethanolic ammonia, to 2,7-dimethyl-8-azapurine (good yield).87... 

Ashfeld and coworkers proposed that the initial phosphinylation of oxime 2 and subsequent Staudinger-like reduction of the tosyl azide forms iminophosphorane 171 (Scheme 5.42k The formation of the phosphoryl bond upon rearrangement is a likely driving force behind the regioselective migration of the trans-oxime substituent (R in 171) to afford the nitriliumion 5. The corresponding anionic phosphoramide is released and then adds to the nitrilium ion amidine 17. A subsequent 1,3-phosphoryl shift leads to the final amidine product 173. 

---