Guanidines from carbodiimides

Homoleptic lanthanide(III) tris(amidinates) and guanidinates are among the longest known lanthanide complexes containing these chelating ligands. In this area the carbodiimide insertion route is usually not applicable, as simple, well-defined lanthanide tris(alkyls) and tris(dialkylamides) are not readily available. A notable exception is the formation of homoleptic lanthanide guanidinates from... 

The synthesis, structures, and reactivity of neutral and cationic mono- and bis(guanidinato)zirconium(rV) complexes have been studied in detail. Either salt-metathesis using preformed lithium guanidinates or carbodiimide insertion of zirconium amides can be employed. Typical examples for these two main synthetic routes are illustrated in Schemes 73 and 74. Various cr-alkyl complexes and cationic species derived from these precursors have been prepared and structurally characterized. 

Biguanides, which are even stronger bases, open new perspectives but they require special preparations. Novel syntheses of poly-N-alkylated biguanides have been devised from carbodiimides, and recent examples of catalyses with soluble and immobilised guanidines and biguanides are presented with emphasis on the transesterification of triglycerides from vegetable oils. 

Barvian, M. R., Showalter, H. D. H., Doherty, A. M. Preparation of N,N -bis(aryl)guanidines from electron deficient amines via masked carbodiimides. Tetrahedron Lett. 1997, 38, 6799-6802. 

Guanidines are also obtained from carbodiimides (which are isomeric with cyanamides) since these react extremely readily with ammonia or amines. Thus, for instance, 7V,7V/,7V//-triphenylguanidine is formed exothermally when diphenylcarbodiimide is mixed with aniline.47 The analogous addition of phenylhydrazine to diphenylcarbodiimide, giving A,A -diphenyl-A"-(phenyl-amino)guanidine, forms the first step in the synthesis of nitrone.48... 

Thus, reaction of carbonimidoyl dihalides with a wide variety of nitrogen-containing substrates can be achieved, and the products obtained range from linear chloroformamidines, guanidines, and carbodiimides to five- and six-membered heterocycles. 

Based on this reactivity, the reaction has been proposed to proceed via the insertion of the carbodiimide into the M-N IxMid of a transient amide complex formed from o-bond metathesis of the precatalyst with the aniline. Turnover occurs via a similar o-bond metathesis of the guanidinate complex with a further equivalent of amine, a reaction that is most likely endothermic based upon pA"a considerations but occurs readily under catalytic conditions [100]. The potential for reversible insertion of the carbodiimide into M-N bonds has been probed by crossover experiments and studies on the current systems do not suggest a reversible insertion step (although this is likely to be a function of the stabihty of the metal-amide generated from carbodiimide extrusion). The molecularity or kinetic competence of... 

The growth centers from carbodiimides are formed through the reaction with an alkali salt, and have the guanidine structure (Equation 7.20). These systems are a part of hquid single-component initiation systems of anionic polymerization of lactams [47]. 

A (pentamethylcyclopentadienyl)iridium chelating guanidinate complex has been conveniently prepared by treatment of [Cp IrCl2]2 with N,N, N"-th-p-tolylguanidine and base in THF at room temperature followed by recrystallization of the green product from toluene and pentane (Scheme 154). Insertion reactions of the product with heterocumulenes (diaryl carbodiimides, aryl isocyanates) have been investigated. It was found that the complex serves as highly active catalyst for the metathesis of diaryl carbodiimides with each other and for the more difficult metathesis of diaryl carbodiimides with aryl isocyanates (cf. Section V.C). ... 

Reaction is terminated at the desired monoaddition-stage by using free guanidine (base), and acetone as solvent (376, 377). Guanidine salts and carbodiimides in dimethylformamide, in spite of the presence of excess of the former, yield 1,2,6-trisubstituted isomelamines (XLIII), presmnably by loss of arylamine from the intermediate labile triguanide (XLII) (375). 

Semicarbazides react in a similar manner. The reaction of carbodiimides with N-methylhydroxylamine affords the expected guanidine derivative resulting from the reaction of the - NH group.555... 

When the less hindered 2,4-tolylene diisocyanate is reacted with a phospholene oxide catalyst linear oligomeric carbodiimides are obtained which have been reacted with a variety of nucleophiles to give poly(ureas), poly(acyl ureas), poly(formamidines) and poly-(guanidines) by addition across the N=C=N group. Also, reaction of the oligomeric carbodiimides with acrylic or methacrylic acid affords linear polymers, which can be further polymerized by free-radical type processes. Also, reaction of the carbodiimide oligomers obtained from 2,4-TDI with adipic acid in DMF produces a polyureid. ... 

Permanently optically active poly(guanidines) 23 (R = Me, n-Hexyl or Ph) are obtained from an achiral carbodiimide monomer 22 using an optically active titanium catalyst. ... 

From 2-Aminophenyl Ketones and Nitriles, Carbodiimides, or Guanidine-1-carbonitrile... 

Carbodiimides react with dicarbonyl compounds (or their sulfur analogues) to give imidazoles [48, 49]. When diimmonium salts (19) are treated with guanidines or O-methylisoureas the initial products are 4,5-dihydroimidazoles, but these are readily aromatized by heating in the presence of triethylamine hydrochloride (Scheme 4.3.10). The mildly acidic conditions result in the loss of one of the amino functions from the intermediate [50]. Yields of 2,5-diaminoimidazoles are usually 60-80% overall. 

Diaminothienopyrimidines 87 were also prepared from thiophenes 30 with cyan-amides under acidic conditions (1990JHC119) or by cyclization of guanidines 88 derived from the corresponding carbodiimides 90 (1991JHC1857). 

Scheme 60 illustrates the proposed catalytic cycles for a samarium(II) silylamide precursor. The first step in both reactions is supposed to be the formation of a bimetallic samarium bis(amidinate) species originating from the reductive coupling of carbodiimide promoted by the Ln(II) complex. The active species is proposed to be a samarium guanidinate and a lanthanide amidinate [70]. 

A series of new l//-pyrazolo[3,4- /]pyrimidin-4(5/f)-ones 84a-l has been regioselectively synthesized in four steps, via a tandem aza-Wittig reaction. The iminophosphorane 81, prepared from 5-aminopyrazole 80, reacted with phenyl isocyanate to give carbodiimide 82, which by reaction with primary or secondary alkylamines, afforded intermediate guanidines 83 that cyclized to the corresponding pyrazolopyrimidinones <04JHC393>. 

The Wittig-type reactions of iminophosphoranes with isocyanates and related compounds have also been extensively used in heterocyclic synthesis. Examples include the preparations of the mesoionic [l,3,4]thiadiazolo[2,3-c][l,2,4]triazines (210) from (209), 0 bicyclic guanidines, e.g. (212), from (211), naphthypyridines (215), (216), and (217) from (213) and (214), 2 pyrido[l,2-f]pyrimido-[4,5-d)pyrimidines (218), 7H-pyrido-[4,3-c]- (219) and 10H-pyrido[3,4-b]- (220) carbazoles, tricyclic fused 2,4-diimino-l,3-diazetidines (222) from the bisiminophosphorane (221), benzotriazepines (225) from (223) and (224), 6 and mesoionic thiazolo-[2,3-b]-1,3,4-thiadiazoles (227) and N,N-bisheteroarylamines from the iminophosphorane (226), derived from 3-amino-4-phenylthiazole-2(3H)-thione. The carbodiimides (229), prepared from the iminophosphorane (228), can be converted into quinolines or a-carboline derivatives depending on the nature of the isocyanate used in the reaction with (228) and the reactions of iminophosphoranes (230) and (231) with aryl and styryl isocyanates provide one-pot syntheses of quinoline, a-carboline, and quinindoline derivatives. 9... 

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