Aryl carbodiimides

Rzepa, H. S., Molina, P., Alajarin, M., Vidal, A. An AMI and PM3 molecular orbital study of the pericyclic reactivity of aryl carbodiimides. Tetrahedron 1992, 48, 7425-7434. 

Versions of carbodiimides patented up to the present time include polycarbodiimides [109, 117, 118, 120], aryl carbodiimides [110-115], alicyclic carbodiimides [110, 111, 119, 121] and blends of carbodiimides and polycarbodiimides [122]. Various additives of this class are commercially available. 

The intramolecular 3 + 2-cycloaddition of iV-(2-azidomethyl)phenyl ketenimines (48) and iV-(2-azidomethyl)phenyl-iV -alkyl(aryl) carbodiimides (49) produced cycloadducts (50) and (51), which underwent dinitrogen extrusion to form indolo[l,2-fljquinazolines and tetrazolo[5,l-fe]quinazolines, respectively, under mild thermal conditions (Scheme 15). ... 

Alkyl- and aryl carbodiimides can be prepared under mild conditions from thioureas with diethyl azodicarboxylate/triphenylphosphine (Mitsunobu reagent), typically in yields of around 80% the by-products are triphenylphosphine sulfide and diethyl hydrazodicarboxylate [1278]. The active intermediate in this system is the betaine 1739, which is formed from diethyl azodicarboxylate (DEAD) and triphenylphosphine. Driven by its charge distribution and its chalcogenophilicity, 1739 reacts with the thiourea 1740 to form the P,S bond in 1741. This energy-rich molecule stabilizes by decomposition into three molecules, namely the two byproducts, triphenylphosphine sulfide and diethyl hydrazodicarboxylate, and the desired carbodiimide 1699. Diphenylcarbodiimide 1699 (R = R = Ph) was prepared from N,N -diphenylthiourea 1740 (R = R = Ph) with DEAD and triphenylphosphine in 65% yield [1278]. 

Dimerization of Carbodiimides. Treatment of alkyl carbodi-imides with anhydrous HBF4-OEt2 in CH2CI2 results in rapid dimerization to tetrafluoroborate salts in 95% yield (eq 13). Basi-fication converts the salts to diazetidines. In the same work, aryl carbodiimides undergo a similar reaction, but substituted quina-zolines are obtained. 

Carbodiimides (cyanamides) —N=C=N— 2140-2125 (s) 2150-2100 (vs) 1460 1150-1140 (vs) Asymmetric stretching of aliphatics Asymmetric stretching of aromatics two bands Symmetrical stretching of aliphatics Symmetric stretching of aryls... 

This method may be applied to the synthesis of a variety of aryl and alkyl carbodiimides. Other catalysts may also be used,10 but the especially active one described here is the one most easily obtained. The method is superior to other methods... 

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). ... 

A useful method to synthesize ten and fourteen-membered ring imides 346 involved an initial condensation of macrocyclic -ketoestes 343 with alkyl or aryl isocyanates and carbodiimides, respectively, in the presence of a base [68]. After a nucleophilic attack of the enolate on the isocyanate C, the resultant amide N anion 344 induced a ring closure by addition to the keto group. Then, the intermediately formed four-membered ring 345 underwent a fragmentation... 

Reaction of 2-cyanomethylpyridine with iV-(l-aryl-l-chloro-2,2,2-trifluoroethyl)-iV -(4-methylphenyl)carbodiimides, and with (1,1,2,2,2-pentachloro- and l,l-dichloro-2,2,2-trifluoroethyl)isocyanates or A-methoxycarbonyl-l,2,2,2-tetrachloro-, — l-chloro-2,2-trifluoroacetaldehyde imines afforded 3-aryl-4-cyano-l-(4-methylphenyl)imino-3-trifluoromethyl-2,3-dihydro-17/-pyrido[l,2-f]pyrimidines and 4-cyano-3-trichloro-, 4-cyano-3-trifluoro-17/-pyrido[l,2-4pyrimidin-l-ones, respectively <2004CHE47>. Refluxing 2-cyanomethylpyridine and iV-(l-aryl-l-chloro-2,2,2-trifluoroethyl)isocyanates in benzene furnished l-aryl-4-cyano-l-trifluoromethyl-l,2-dihydro-3//-pyrido[l,2-4pyrimidin-3-ones. However, when the solution of the isocyanate was added dropwise to the solution of 2-cyanomethylpyridine, and the reaction mixture was then treated with NEt at room temperature, the isomeric 3-aryl-4-cyano-3-trifluoromethyl-2,3-dihydro-l//-pyr-ido[l,2-dpyrimidin-l-ones were obtained. Reaction of l-(acetyl- and benzoylmethylene)-6,7-dimethoxy-l,2,3,4-tetra-hydroisoquinolines with PhCONCS yielded 1-acetyl-, 1 -benzoyl-9,10-dime thoxy-3-pheny 1-6,7-dihydro-2//-pyrimido[6,l- ]isoquinoline-2-thiones <2003SL2369>. 

An alternative strategy for the synthesis of these tricyclic compounds involves the reaction of the azidoalkenyl-functionalized furo[3,2-A]pyrrole 30, which reacts with triphenylphosphine to give the corresponding iminophos-phoranes 31 these upon reaction with aryl isocyanates give the pyrrolo[2, 3 4,5]furo[3,2-r-]pyridines 32, via the corresponding carbodiimides which are not isolated < 1994H(37) 1695, 1992M807> (Scheme 9). 

V-(Ethoxycarbonylmethyl)carbodiimides, obtained from the reaction of iminophos-phoranes with aryl isocyanates, undergo cyclization when treated with an excess of tetra-n-butylammonium fluoride at room temperature to yield l,3-oxazlin-5-ones [75] (Scheme 3.9). The ammonium fluoride probably enhances the electrophilic character... 

This is a modification of the new general method for the preparation of carbodiimides by the thermolysis of 5-substituted 4-aryl-l,2,3,5-thiaoxadiazole-l-oxides described recently by Rajagopalan and Advani, whereby the 4,5-diphenyl-l,2,3,5-thiaoxadiazole-l-oxide, which is formed in this reaction, is not isolated but decomposed in situ. 

Finally, the synthesis of 4//-3,l-benzoxazines 239 via a tandem aza-Wittig reaction (Scheme 89) should be mentioned. Carbodiimide 238 or isocyanate generated by an intramolecular aza-Wittig reaction bears an o-hydroxymethyl group on the A(-aryl substituent this OH attacks the carbodiimide C intramolecularly with cyclization to give a 3,1-benzoxazine (91S21). 

Scheme 65) <60G1290>. Oxadiazolines (156) are produced by cycloaddition of cyanamides and nitrile oxides aryl (Scheme 66) <66JPR22l>. Thus, for un- and monosubstituted cyanamides, cycloaddition occurs to the C=N double bond of a tautomeric carbodiimide form rather than to a nitrile triple bond. On the other hand, dicyandiamide (157) and benzonitrile oxide furnish (158) (Scheme 67). 

A successful method for preparing 1,3-thiazetidines is the cycloaddition of carbodiimides with isocyanates. The cycloadduct 151 was derived by the interaction of carbodiimide 152 and tosyl isothiocyanate . Reaction of 152 with methyl or phenyl isothiocyanate preferentially leads to iminotriazine-thiones. Cycloaddition between aryl isothiocyanates and dicyclohexylcar-bodiimide produced 153. ... 

The addition of C-4 or C-6 is not a common route to pyrimidines, although in an example of this approach, 4-aryl-2-chloropyrimidines 622 were prepared from acetophenone cyanoimines 621, where the C-6 carbon came from DMF via the Vilsmeier reagent <2002SC3011>. The starting acetophenone cyanoimines were readily prepared from the analogous acetophenones by successive treatment with titanium tetrachloride and bis(trimethylsilyl)carbodiimide <2002SC3011>. 

Cyclocarbonylation of o-iodophenols 503 with isocyanates or carbodiimides and carbon monoxide in the presence of a catalytic amount of a palladium catalyst (tris(dibenzylideneacetone)dipalladium(O) Pd2(DBA)3) and l,4-bis(di-phenylphosphino)butane (dppb) resulted in formation of l,3-benzoxazine-2,4-diones 504 or 2-imino-l,3-benzoxazin-4-ones 505 (Scheme 94). The product yields were dependent on the nature of the substrate, the catalyst, the solvent, the base, and the phosphine ligand. The reactions of o-iodophenols with unsymmetrical carbodiimides bearing an alkyl and an aryl substituent afforded 2-alkylimino-3-aryl-l,3-benzoxazin-4-ones 505 in a completely regioselective manner <1999JOC9194>. On the palladium-catalyzed cyclocarbonylation of o-iodoanilines with acyl chlorides and carbon monoxide, 2-substituted-4f/-3,l-benzoxazin-4-ones were obtained <19990L1619>. 

The palladium-phosphine-catalyzed cycloaddition reactions of vinyloxetanes 530 with aryl isocyanates or diaryl-carbodiimides led to 4-vinyl-l,3-oxazin-2-ones 531 or l,3-oxazin-2-imines 532, respectively (Scheme 101). In the absence of phosphine ligands (PPhs, bis(diphenylphosphino)ethane (DPPE), l,3-bis(diphenylphosphino)propane (dppp), no conversion of heterocumulenes was observed. Starting from fused-bicyclic vinyloxetanes, both types of cycloadditions proceeded in a highly stereoselective fashion, affording only the r-isomers of alicycle-condensed 1,3-oxazine derivatives <1999JOC4152>. 

Iminophosphoranes derived from readily available ot-azidocinnamates react with aroyl chlorides to give the corresponding 2-aryl-4-arylidene-5(4//)-oxazolones 37 2 500,501 AjteiTjatively, these iminophosphoranes are converted to the corresponding 2-arylamino-4-arylidene-5(4//)-oxazolones 373 via heterocyclization of an intermediate carbodiimide as shown in Scheme 7.119 (Table 7.32, Fig. 7.43). ° ... 

Diketene is of course a masked form of acetoacetic ester, and as such reacts in much the expected manner with a variety of mono- and di-nucleophiles. Aromatic and heteroaromatic amines, and phenols, for example, give acetoacetanilides and aryl acetoacetates the latter can be cyclized in excellent yield to coumarins while reaction of the former with excess of diketene followed by cyclization gives dioxopyridines (e.g. equation 164). Amidines, ureas, thioureas, S- alkylthioureas and carbodiimides also react with diketene to give pyrimidines e.g. equation 165), although in the case of amidines, S- alkylthioureas and carbodiimides the initially formed products are 1,3-oxazines which are converted into pyrimidines on subsequent treatment with acid or base. 

Addiert man Aryl-isocyanate an Triphenyl-phosphan-(2-benzimidazolyl-methylimin) (I), so erhalt man 2-Aminocarbony 1-1 -arylimino-2,3-dihydro-lH-benz-imidazole)(IlI). Die Entstehung der Produkte wird iiber ein Carbodiimid-Zwischenprodukt II interpretiert520. 

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