Catalyst carbodiimidation

Carbodiimide formation is markedly accelerated when phosphine oxides (R PO) or phosphates are used as catalysts. Intermediates with P—NR bonds have been postulated as iatermediates ia these reactioas (59,60). 

Olefin isomerization can be catalyzed by a number of catalysts such as molybdenum hexacarbonyl [13939-06-5] Mo(CO)g. This compound has also been found to catalyze the photopolymerization of vinyl monomers, the cyclization of olefins, the epoxidation of alkenes and peroxo species, the conversion of isocyanates to carbodiimides, etc. Rhodium carbonylhydrotris(triphenylphosphine) [17185-29-4] RhH(CO)(P(CgH )2)3, is a multifunctional catalyst which accelerates the isomerization and hydroformylation of alkenes. 

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... 

Activating agents, such as trifluoroacetic anhydride 1,1 -carbonyldiimidazolc carbodiimides sulfonyl, tosyl, and picryl chlorides and a range of phosphorus derivatives can promote direct solution reactions between dicarboxylic acids and diols or diphenols in mild conditions. The activating agents are consumed during the reaction and, therefore, do not act as catalysts. These so-called direct polycondensation or activation polycondensation reactions proceed via the in situ transformation of one of the reactants, generally the carboxylic acid, into a more... 

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). ... 

Amidinate complexes of copper(I) and copper(II) have been found to catalyze the polymerization of carbodiimides. The copper catalysts are highly active even under air and oxygen. It was shown that the catalytic activity of an air-stable copper(II) amidinato complex is almost equal to that of reported air-sensitive titanium(IV) amidinate initiators. Scheme 225 illustrates the proposed reaction mechanism. ... 

The treatment of isocyanates with 3-methyl-l-ethyl-3-phosphoIene-l-oxide (59) is a useful method for the synthesis of carbodiimides in good yields. The mechanism does not simply involve the addition of one molecule of isocyanate to another, since the kinetics are first order in isocyanate and first order in catalyst. The following mechanism has been proposed (the catalyst is here represented as... 

Majetich and Hicks <96SL649> have reported on the epoxidation of isolated olefins (e.g., 61) using a combination of 30% aqueous hydrogen peroxide, a carbodiimide (e.g., DCC), and a mildly acidic or basic catalyst. This method works best in hydroxylic solvents and not at all in polar aprotic media. Type and ratios of reagents are substrate dependent, and steric demand about the alkene generally results in decreased yields. 

Iron pentacarbonyl has been shown to be a catalyst for the reaction of organic azides with isocyanides, giving carbodiimides 127) [Eq. (21)]. 

Like the carbodiimide method, the mixed anhydride method results in an amide complex (Table 5, Figure 17). The acid-containing hapten is dissolved in a dry, inert, dipolar, aprotic solvent such as p-dioxane, and isobutyl chloroformate is added with an amine catalyst. The activated mixed anhydride is chemically stable and can be isolated and characterized. The aqueous protein solution is added to the activated acid and the pH is maintained at around 8.5. A low temperature (around 10 °C) is necessary during the reaction to minimize side reactions. 

COOH groups of the PE (PAA or PGA) and the -NH2 moieties of the pre-loaded protein, using l-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) as a catalyst [99]. Negligible enzyme desorption (<0.1 %) is observed from cross-linked lysozyme-loaded MS spheres after exposing the samples to an aqueous solution for 48 h, while about 25 % of the immobilized lysozyme is desorbed under the same conditions when the lysozyme is not cross-linked. 

Thioureas are most commonly prepared from reaction of isothiocyanates with amines. Also there are some reports on reactions of anime or carbodiimides with several thionating reagents. AA -Disubstituted thioureas bearing double NH groups have been developed as sensors, and as catalysts because of their hydrogen bonding ability. A,A -Disubstituted thiourea-linked sugar chains have been prepared by the reaction of isothiocyanate with amine. 

Activated esters (see Section 2.9) with 1-hydroxybenzotriazole as a catalyst are employed — pentafluorophenyl or 4-oxo-3,4-dihydrobenzotriazin-3-yl esters in particular for continuous-flow systems and special cases such as dicarboxylic amino acids. Other activated esters are not reactive enough. An alternative is preparation of benzotriazolyl esters using a carbodiimide followed by addition of the solution to the peptide-resin. 

During their study of the synthesis of Paludrine-analogues, Curd, Rose et al. (58) observed that ammonolysis in ethanol of the S-methylisothio-urea (XVIII R = p-ClCeH4 Alk = isoPr) gave, instead of the expected Paludrine (XIX), the 0-ethylisourea (XXI). Their interpretation of this result (postulating the intermediate formation of a carbodiimide (XX), and subsequent addition of ethanol) appears open to question, however, because carbodiimides are known to react with alcohols only with difficulty except in the presence of catalysts (767, 373). In the absence of ethanol, aminolysis of XVIII by isopropylamine yields 1-p-chloro-phenyl-4,5-diisopropylbiguanide as expected (58). 

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>. 

Hofmann in 1885 [26] reported that heating of isocyanate esters in the absence of catalysts gave products which analyzed correctly for carbodiimides. 

Prolonged heating of free isocyanates in the absence of catalysts has been reported recently to give poor yields of carbodiimides unless a slow stream of nitrogen was passed through the boiling isocyanate [18]. In the presence of phosphorus catalysts [18, 19, 27-39], aromatic carbodiimides are obtained in high yield under mild conditions from isocyanates but not isothiocyanates [18]. Aliphatic isocyanates react more slowly, but improved yields are obtained in... 

Conversion of isocyanates into carbodiimides with isopropyl methyl-phosphonofluoridate as catalyst [77]. 

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... 

Since depsipeptides, in contrast to classical peptides, contain units constructed from amino and hydroxy acid residues, the various methods for their preparation are generally pathways involving the formation of ester bonds. The novel achievements in this area discussed (vide infra) are associated with further developments in the mixed anhydride technique, the application of effective catalysts in the carbodiimide procedure, and adaptation of the known Mitsunobu reaction to the depsipeptide case. A number of significant and efficient esterification procedures utilized for the preparation of depsipeptides are considered. 

These problems were solved by Miller,[104 who developed a direct isourea-mediated 3-elimination process to prepare DHA derivatives. The reaction involves treatment of a Ser (or Thr) peptide 30 with a carbodiimide (1.1 equivalents) in the presence of copper(I) chloride as a catalyst to give a AAla (or AAbu) derivative 31, respectively, in good yield (Scheme 11). 

Support-bound primary or secondary aliphatic alcohols can be acylated under conditions similar to those used in solution, provided that these conditions are compatible with the chosen linker. For instance, acids can be activated with a carbodiimide either as symmetric anhydrides or as O-acylisoureas, which quickly react with alcohols in the presence of a catalyst, such as DMAP or another base, to yield esters (Table 13.12). Further acid derivatives suitable for esterification reactions on solid phase include acyl halides and imidazolides. HOBt esters react only slowly with alcohols, but enable the selective acylation of primary alcohols in the presence of secondary alcohols (Entry 5, Table 13.12). 

---