Guanidines reaction with carbodiimides

Amidines and cyclic amidines are also converted into 1,2,4-thiadiazoles by reaction with isothiocyanates, imino-sulfenyl chlorides, di- and trichloromethyl sulfenyl chlorides, and carbon disulfide in the presence of sulfur. Ureas, thioureas, guanidines, carbodiimides, and cyanimides react with chlorocarbonylsulfenyl chloride to produce 1,2,4-thiadiazol-5-one derivatives in another example of a type B synthesis <1996CHEC-II(4)307>. 

Reactions with Ammonia, Amines, Amine Derivatives and Azides. Ammonia, primary and secondary amines react with carbodiimides to give guanidine derivatives. For example, firom primary amines the guanidine derivative 559 is obtained. 

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... 

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... 

While uncatalyzed reaction of sulfonamides and carbodiimides is limited to aliphatic carbodiimides, the CuCl-catalyzed coupling is more general reaction (Scheme 3.73). CuCl-catalyzed coupling of arylsulfonamides 274 with carbodiimides 275 readily proceeded with DCC, DIC, and DPTC obtaining the corresponding guanidines 276 (Table 3.36), but not with sterically hindered carbodiimides... 

Also in Osaka, another former student of Akabori, professor Tetsuo Shiba (Plate 43) and his associates developed a procedure for the preparation of lanthionine-containing peptides and applied it, in 1988, to the synthesis of the antibiotic nisin (p. 223). In Tokyo, at Rikkyo University, professor Ichiro Muramatsu, also from the Akabori school, proposed a rapid method of synthesis and discovered novel side reactions, such as the formation of guanidine derivatives during coupling with carbodiimides. 

The introduction of carbodiimides (Sheehan and Hess 1955), particularly dicy-clohexylcarbodiimide (DCC, DCCI) as reagents for the formation of the peptide bond was a major event in the history of peptide synthesis. The novel feature of coupling reagents was that they could be added to the mixture of the carboxyl component and the amine component. Thus, activation and coupling proceed concurrently. While amines do react with carbodiimides (yielding guanidine derivatives) the rate of this reaction is negligible when compared with the rapid rate observed in the addition of carboxylic acids to one of the double bonds of a carbodiimide ... 

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... 

Wang H, Ye S, Jin H, Liu J, Wu J (2011) An expeditious approach to l-(isoquinolin-l-yl) guanidines via a three-component reaction of 2-alkynylbenzaldehyde, sulfonohydrazide, with carbodiimide. Tetrahedron 67 5871-5877... 

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). ... 

The condensation of biguanide and cyanamide (which, in its diimino-form, may be regarded as the parent compound of carbodiimides (373)) has apparently not been studied. The patent literature (85,109) describes the manufacture of melamine by heating mixtures of biguanide or guanidine or their salts with cyanamide or dicyandiamide to 140—240°. but since each of these compounds alone yields melamine under these conditions, the course of these reactions is not clear. The only valid example appears to be the condensation of p-chlorophenylcyanamide and p-chlorophenylbiguanide to 2.4-di(p-chlorophenyl)melamine (304). 

Guanidines may also be formed by reaction of amines with carbodi-imides. This reaction is limited by the availability of carbodiimides, which are usually formed by several methods,24 including dehydration of ureas with the Edward Burgess reagent 11 (Scheme 9).25-27... 

A carbodiimide-grafted polystyrene resin was reacted with tetramethyl-guanidine to give an interesting biguanide structure (Scheme 13). This was assayed as a catalyst for a transesterification reaction.33 Incidentally, resin-bound guanidines are useful bases for processes involving resin capture.34... 

In the reaction of iridium complexes 54 with two equivalents of carbodiimides, mixtures of cyclic carbamate complexes 55 and organometaUic guanidinates 56 are obtained. ... 

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. ... 

The aza-Wittig reaction is also used to form polymers with pendant carbodiimide groups. For example, reaction of the polymeric azide 31 with benzyl isothiocyanate and triphenylphosphine gives the corresponding carbodiimide 32, a precursor for oligomeric guanidines." ... 

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