Amidine, resistance

Surprisingly, acetylation in hot pyridine yields the pyridinium salt 10. The amino group has amidine character and is resistant to diazotization, and condenses only with reactive aldehydes such as formaldehyde and trichloroacetaldehyde.41... 

Increasing numbers, world-wide, of nosocomical (hospital-acquired) infections are caused by MRSA strains [255], Such strains particularly affect patients in intensive-care units [246], In the UK, gentamicin resistance suddenly appeared in 1976 and MGRSA strains caused severe major hospital outbreaks. It has been proposed [186, 227, 229] that, since resistance to nucleic acid-binding (NAB) compounds, such as chlorhexidine, amidines,... 

The preparation and reactions of the azine, phenylhydrazone, and phenyl-semicarbazone of 4-amino-5-formyl-2-methyltriazole proceeded normally. One acetal has been prepared as follows. 4-Amino-3-benzyl-5-formyltriazole and boron trifluoride (as diethyl ether complex), stirred in methanol, gave 4-amino-3-benzyl-5-dimethoxymethyltriazole (20°C, 6 hr, 53%) and a dimeric by-product, 4-amino-3-benzyl-5-(3-benzyl-5-dimethoxytriazol-4-ylimino-methyl)triazole [73JCS(P1)2037]. The amino group in 4-aminotriazole-5-carbaldehydes lends itself readily to the formation of amidines and imidates (Section III,B,1), but it resists acylation. 

These include amitraz (110), prepared from 54, a member of the form amidine class, active against mites and ticks, that have replaced organophosphorus compounds. Notably, amitraz is active against newer strains of pyrethroid-resistant ticks. The reaction of diphenylamine (8) with sulfur in the presence of iodine as catalyst yields the anthelmintic (worming agent) phenothiazone (phenothiazine) (111) (Scheme 24). It is too toxic for human use, though it is an intermediate in the production of antipsychotic drugs. 

A carboxylic acid derivative which also contains an activated neighbouring halo atom may be cyclized by warming with an amidine (or guanidine) or 2-aminopyridine (a cyclic amidine). In some reactions of this type, it is advantageous to add a base such as TEA. The chlorine atom of the thienopyridine (6[Pg.422]

Both 1,2,3,5- and 1,3,2,4-dithiadiazolylium salts are susceptible to hydrolysis, although the ease of hydrolysis is affected by the solid-state structure and hence the counter-ion. Layered structures (Types B-D) with strong secondary interactions are remarkably resistant to hydrolysis [90JCS(D)2793], with some samples retaining their luster even after standing in water for 20 minutes. Class A salts tend to be more susceptible to hydrolysis, eventually yielding the amidine (IR spectrum), sulfur, and S02. 

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... 

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