Imide amidine

Although the mechanism of the cyclotrimerization of substituted amidines resembles that of imidates, amidines are only of limited use in the synthesis of 1,3,5-triazines. 

Carboxylic acids in the order -COOH, logues, then sulf(onic, inic)-, phosph(onic, ink)-, ars(onic inic)-acids Acid derivatives in the order anhydrides, esters, halides, amides, hydrazides, imides, amidines etc. 

Amidines are best made in two stages a nitrile reacts with dry HCl and anhydrous alcohols to give an imidic ester (imino-ether) which yields an amidine with NH3. 

Reactions. Although carbapenems are extremely sensitive to many reaction conditions, a wide variety of chemical modifications have been carried out. Many derivatives of the amino, hydroxy, and carboxy group of thienamycin (2) have been prepared primarily to study stmcture—activity relationships (24). The most interesting class of A/-derivatives are the amidines which are usually obtained in good yield by reaction of thienamycin with an imidate ester at pH 8.3. Introduction of this basic but less nucleophilic moiety maintains or improves the potency of the natural material while greatiy increasing the chemical stabiUty. Thus /V-formimidoyl thienamycin [64221-86-9] (MK 0787) (18), C 2H yN204S, (25) was chosen for clinical evaluation and... 

Cyanopyridazines add ammonia, primary and secondary amines and hydroxylamine to give amidines or amidoximes. Substituted amides, thioamides and carboximidates can be also prepared. With hydrazine, 3-pyridazinylcarbohydrazide imide is formed and addition of methylmagnesium iodide with subsequent hydrolysis of the imine affords the corresponding pyridazinyl methyl ketone. 

Peifluorinated nitriles are highly electrophihc compounds because of the adjacent electron-accepting substituent Therefore, the addition of amines, alcohols, and mer-captans forming amidines, imidates, and thiobnidates is well-documented [63]. 

Theoretically, valence isomerization of 3//-azepincs can give rise to 2-azabicyclo[3.2.0]hepta-2,6-dienes 20 and/or the isomeric fused azetines, 6-azabicycIo[3.2.0]hepta-2,6-dienes 21. Practically, however, 2-alkoxy- and 2-amino-3//-azepincs 19, on photolysis, yield the 2-azabicyclic systems 20 exclusively, since such structures are stabilized by imidate or amidine resonance.238... 

The amidines 10, prepared by condensation of the corresponding imidates with aminoacetal-dehyde dimethyl acetal, undergo cyclization with a variety of acids to l//-3-benzazcpin-2-amines 11 45 Method A has proved to be successful on an industrial scale. 

The chemistry of amidines and imidates The chemistry of cyanates and their thio derivatives (2 parts)... 

Carbonsaure-imid-ester Oder deren Salze werden durch Natriumboranat in neutralem Medium zu 0,N-Acetalen (s. S. 436 f.) (bzw. Aldehyden) Oder Aminen reduziert. Amidine und Imid-chloride gehen in Amine iiber, Formazane in Amid-hydrazone. 

Titanium imido complexes supported by amidinate ligands form an interesting and well-investigated class of early transition metal amidinato complexes. Metathetical reactions between the readily accessible titanium imide precursors Ti( = NR)Cl2(py)3 with lithium amidinates according to Scheme 84 afforded either terminal or bridging imido complexes depending on the steiic bulk of the amidinate anion. In solution, the mononuclear bis(pyridine) adducts exist in temperature-dependent, dynamic equilibrium with their mono(pyiidine) homologs and free pyridine. 

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. 

A. Gautier, M. Miocque, C.C. Farnoux, 1975, Chapter 7 in The Chemistry of Amidines and Imidates , Editor S. Patai, J. Wiley and Sons, New York... 

N-Trimethylsilylamides or lactams 344 react with sodium trimethylsilanolate 96 to generate the anhydrous N-sodium salts 345 and hexamethyldisiloxane 7 in practically quantitative yield [125]. Likewise, silylated succinimide 201 is converted by sodium trimethylsilanolate 96 into hexamethyldisiloxane 7 and the anhydrous sodium salt 346, which reacts with aldehydes RCHO (R=C2H5, n-C Hy), in the presence of catalytic amounts of 96 to give, via 346, the silylated adducts 347 in 43-62% yield [125]. The imide chloride 348 gives, analogously, sodium chloride and 7 and the N-sodium salt 349, which condenses in situ with unreacted imide chloride 348 to give 91% of the amidine 350 [126] (Scheme 4.46). 

The amidine bond formed is quite stable at acid pH however, it is susceptible to hydrolysis and cleavage at high pH. A typical reaction condition for using imidate crosslinkers is a buffer system consisting of 0.2 M triethanolamine in 0.1 M sodium borate, pH 8.2. After conjugating two proteins with a bifunctional imidoester crosslinker, excess imidoester functional groups may be blocked with ethanolamine. 

J. Oszczapowicz, in The Chemistry of Amidines and Imidates (Eds. S. Patai and Z. Rappoport), Vol. 2, Chap. 12, Wiley, Chichester, 1991 and references cited therein. 

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