Carbodiimides compounds using

Figure 5.36 ASBA contains a primary amine group that may be conjugated to carboxylate compounds using the carbodiimide EDC. Subsequent exposure to UV light initiates the photoreaction leading to covalent crosslinks.

Figure 18.21 Biotin-PEG -amine compounds can be used to modify carboxylate- or aldehyde-containing compounds using a carbodiimide reaction.

Cyclization of A-acyl-oc-amino acids under acidic reaction conditions is sometimes problematic due to the difficulty in separation of the desired oxazolone from by-products while avoiding decomposition of the reactive oxazolone. This finding is particularly true in the case of 2-phenyl-5(47i)-oxazolone, an interesting compound that is a very useful intermediate to prepare a variety of novel products. The use of carbodiimides as dehydrating agents has been described as a means to improve the results. In particular, treatment of an A-acyl-a-amino acid with A-cyclohexyl-A -2-(A-methylmorpholinio)ethylcarbodiimide p-toluensulfo-nate (Scheme 7.25) is especially useful as a general synthesis of the desired saturated 5(47i)-oxazolones 101 in excellent yields.This same carbodiimide was used to study the kinetics of the formation of saturated 5(47i)-oxazolones from N-protected dipeptides... 

Other reactive chlorine compounds used in the synthesis of carbodiimides include 2,4-dichloro-5-nitropyrimidine, ° 1-chlorobenzothiazole, 2-chlorobenzothiazole, 2-chloro-... 

An antioxidant used in the S5mthesis of a carbodiimide compound. The antioxidant is added during the synthesis. A suitable... 

The hydrolysis inhibitor is added for preventing the acoustic apparatus housing from easily decomposing due to moisture in air during the period of use. Preferred hydrolysis inhibitors are car-bodiimides. A carbodiimide compound can be melt-kneaded with the biodegradable polymer compound. Examples are N,N -dicy-clohexylcarbodiimide or N,N -diisopropylcarbodiimide (22). For definitely obtaining the required mechanical strength a rubber component is added. 

The formal [2+2+1] cocyclization of alkenes, alkynes and CO by transition metal complexes has been used as a powerM tool for the synthesis of cyclopentenones (Scheme 10.1a) [15]. Other variants of C=C bond like allene, carbonyl or imino moiety can also be used in place of alkene or as a partner of alkene to synthesize 4-or 5-alkylidene cyclopentenones, [16] y-lactones [17] or y-lactams, [18] respectively. Catalytic [2+2+1] cocyclization can also be used with full efficiency to construct heterocyclic compounds using het-erocumulenic compounds such as carbodiimides and/or isocyanates with alkynes and CO (Scheme 10.1c). 

Another method used to remove phosgene substitutes from the desired products is to destroy them with appropriate nucleophiles such as water or alcohols. This method can, of course, only be applied when the product is insensitive to these nucleophiles, as is the case for carbamates, carbonates, ureas, cyanides, isocyanides, and alkyl chlorides. Chloroformates, carbamoyl chlorides, isocyanates, acyl chlorides, N-carboxylic anhydrides, and carbodiimides, on the other hand, cannot be purified by this method. Consequently, a synthesis of these compounds using phosgene is worthy of consideration. 

Bisa2iridine compounds and A/-(2-chloroethyl)carbodiimides have also been prepared using isocyanide dichlorides and ethyleneimine (178,179). The iodide-cataly2ed rearrangement of the formerly mentioned compounds provides a method for preparing the tetrahydroimida2oimida2ole system ... 

A similar approach, i.e., carbodiimide insertion into M-N bonds was used to prepare unusual zirconacarboranes containing guanidinate ligands. In an alternative approach, these compounds were also synthesized by the route outlined in Scheme... 

A full development of the rate law for the bimolecular reaction of MDI to yield carbodiimide and CO indicates that the reaction should truly be 2nd-order in MDI. This would be observed experimentally under conditions in which MDI is at limiting concentrations. This is not the case for these experimements MDI is present in considerable excess (usually 5.5-6 g of MDI (4.7-5.1 ml) are used in an 8.8 ml vessel). So at least at the early stages of reaction, the carbon dioxide evolution would be expected to display pseudo-zero order kinetics. As the amount of MDI is depleted, then 2nd-order kinetics should be observed. In fact, the asymptotic portion of the 225 C Isotherm can be fitted to a 2nd-order rate law. This kinetic analysis is consistent with a more detailed mechanism for the decomposition, in which 2 molecules of MDI form a cyclic intermediate through a thermally allowed [2+2] cycloaddition, which is formed at steady state concentrations and may then decompose to carbodiimide and carbon dioxide. Isocyanates and other related compounds have been reported to participate in [2 + 2] and [4 + 2] cycloaddition reactions (8.91. 

A first terminal imido complex of nickel (121) was prepared according to Equation (3).468 The synthesis goes via the Ni11 amido compound (122) and uses the steric bulk of the arylimido group for stabilization. The Ni11 center in (121) is planar and three-coordinate. Reaction of (121) with CO or benzyl isocyanide leads to formal nitrene transfer with formation of (124) and (125), respectively. Further reaction with CO liberates the isocyanate and carbodiimide (Equation (4)). 69... 

Carboxylic acids may be covalently modified with adipic acid dihydrazide or carbohydrazide to yield stable imide bonds with extending terminal hydrazide groups. Hydrazide functionalities don t spontaneously react with carboxylate groups the way they do with aldehyde groups (Section 4.5, this chapter). In this case, the carboxylic acid first must be activated with another compound that makes it reactive toward nucleophiles. In organic solutions, this may be accomplished by using a water-insoluble carbodiimide (Chapter 3, Section 1.4) or by creating an intermediate active ester, such as an NHS ester (Chapter 2, Section 1.4). 

Hydrazide-containing compounds also can be coupled to carboxylate groups using a carbodiimide-mediated reaction. Using bifunctional hydrazide reagents, carboxylates can be modified to possess terminal hydrazide groups able to conjugate with other carbonyl compounds (Chapter 4, Section 8). 

Figure 3.5 The organic-soluble carbodiimide DCC is often used to create amide bonds, especially between water-insoluble compounds.

Cascade Blue cadaverine and Cascade Blue ethylenediamine both contain a carboxamide-linked diamine spacer off the 8-methoxy group of the pyrene trisulfonic acid backbone. The cadaverine version contains a 5-carbon spacer, while the ethylenediamine compound has only a 2-carbon arm. Both can be coupled to carboxylic acid-containing molecules using a carbodiimide reaction (Chapter 3, Section 1). Since Cascade Blue derivatives are water-soluble, the carbodiimide EDC can be used to couple these fluorophores to proteins and other carboxylate-containing molecules in aqueous solutions at a pH range of 4.5-7.5. The reaction forms amide bond linkages (Figure 9.39). 

---