Carbodiimide from ureas

Carbodiimide, diphenyl, 49, 70 Carbodiimides from ureas with tolu-enesulfonyl chloride and tri-ethylamine, 48, 86... 

General procedure. Carbodiimides from ureas or thioureas [1262] Equimolar amounts of urea or thiourea, tetrachloromethane, triethylamine, and triphenylphosphine (in... 

Pyrolysis of amidino dichlorides (from urea and phosgene) to carbodiimide [67],... 

The alkyl-, alky laryl- and diarylcarbodiimides are the diimides derived from carbon dioxide, however, no direct formation of carbodiimides from amines and carbon dioxide is known. Interestingly, carbodiimides can be obtained from amines and carbon dioxide via a switteri-onic titanium complex (see Section 2.2.8). The major starting materials for the synthesis of carbodiimides are isocyanates, 1,3-disubstituted ureas or 1,3-disubstituted thioureas. The synthesis of isocyanates requires the use of the toxic carbonyl chloride or its oligomers. A book on the synthesis and reactions of isocyanates appeared in 1996. ... 

Reviews on the synthesis and chemistry of carbodiimides are given in [1248-1250]. Carbodiimides are mainly synthesized in one of three ways from ureas or thioureas, from isocyanates, or from isocyanides. Several reagents have been employed in carbodiimide synthesis phosgene [1252, 1253], dimethylphosgenimi-nium chloride [1254], tiiphosgene [561, 562], phosphorus pentoxide [1255], phos-phoryl chloride [1256], triphenylphosphine dibromide [758, 1257-1261], triphenylphosphine/tetrahalomethanes [1262, 1263], iminophosphoranes [1264-1277], Mitsunobu reagent [1278, 1279], p-tosyl chloride [1280, 1281], and CDC [1137] oxidative additions have also been used [1282-1284]. 

General procedure. Carbodiimides 1699 from ureas 1696 [1254] To a suspension of the urea 1696 (1 equiv.) and dimethylphosgeniminium salt 1697 (1 equiv.) in di-chloromethane (0.3 m) at 0 °C under argon atmosphere was added a solution of... 

Grassie and co-workers a.l23, a.l24] found that under inert conditions at temperatures above about 210 °C the polyurethane linkage disappears without any volatile products being formed, and the initial degradation step is seemingly a simple depolymerisation reaction. The two monomers are the primary products, and all the other products, which include carbon dioxide, butadiene, tetrahydrofuran, dihydrofuran and water as volatile products and carbodiimide and urea amide in the condensed phase, are formed from the monomers in a complex set of secondary reactions while they are diffusing from the hot polymer. This is unlike under oxidative conditions, whereby the first step involves the scission of the polyurethane molecule into primary amine, carbon dioxide and propenyl ether species, the latter leading to propene formation. The mechanism is reduced to a... 

Ionic polymers are also formulated from TDI and MDI (43). Poly(urethane urea) and polyurea ionomers are obtained from divalent metal salts of /)-aminohen2oic acid, MPA, dialkylene glycol, and 2,4-TDI (44). In the case of polyureas, the glycol extender is omitted. If TDI is used in coatings apphcations, it is usually converted to a derivative to lower the vapor pressure. A typical TDI prepolymer is the adduct of TDI with trimethyl olpropane (Desmodur L). Carbodiimide-modified MDI offers advantages in polyester-based systems because of improved hydrolytic stabihty (45). Moisture cure systems based on aromatic isocyanates are also available. 

Carbodiimides are, in general, useful compounds for effecting certain dehydrative condensations, e.g., in the formation of amides, esters, and anhydrides. These two crystalline water-soluble carbodiimides are especially useful in the synthesis of peptides and in the modification of proteins. The excess of reagent and the co-product (the corresponding urea) are easily separated from products with limited solubility in water. The hydrochloride is best employed in nonaqueous solvents (methylene chloride, acetonitrile, dimethylformamide). The methiodide is relatively stable in neutral aqueous systems, and thus is recommended for those media. 

A carbodiimide is added to the two reacting species. The urea generated from dicyclohexylcarbodiimide is insoluble and voluminous, so it is often replaced by diisopropylcarbodiimide, which generates a soluble urea. The soluble carbodiimide ethyl-(3-dimethylaminopropyl)-carbodiimide hydrochloride (see Section 1.16) is suitable but expensive. Efficiency of coupling is greater in dichloromethane than in dimethylformamide. There is also the option of adding 1-hydroxybenzotriazole to minimize the side reactions of A-acylurca (see Section 2.12), cyano (see Section 6.15), and aspartimide (see Section 6.13) formation. 

A very special example is shown in Scheme 35 with the formation of bisglucosylcarbodiimides (61) from 2-azidoglucose via an aza-Wittig reaction with CO2 or CS2. Subsequent addition of water affords bisglucosyl ureas (62) (64AG227). Further examples for the syntheses of carbodiimides are presented in Section VI. 

Exercise 15-25 The equilibrium for the formation of urea compounds from the hydrolysis of substances called carbodiimides is a thermodynamically favorable reaction ... 

A related series of 5-substituted-2-amino-oxadiazole compounds have also been prepared in a one-pot procedure using a microwave-assisted cyclisation procedure (Scheme 6.26)164. Rapid preparation of the pre-requisite ureas from the mono acyl hydrazines and various isocyanates (or the isothiocyanate) was easily achieved by simple mixing. The resulting products were then cyclo dehydrated by one of the two procedures either by the addition of polymer-supported DMAP and tosyl chloride or alternatively with an immobilised carbodiimide and catalytic sulphonic acid. Purity in most cases was excellent after only filtration through a small plug of silica but an SCX-2 cartridge (sulphonic acid functionalised - catch and release) could be used in the cases where reactions required additional purification. 

The solvent is removed at the rotary evaporator, and the resulting residue is purified by chromatography. It can be advisable to filter the precipitate of N, iV -dicyclohexylurea8—formed when DCC is used—before removing the solvent. In order to avoid interferences from unreacting carbodii-mide, it can be advisable to transform it in the corresponding urea by careful addition of oxalic acid either solid or in a solution in methanol—to the stirred reaction mixture. Addition of oxalic acid produces a copious evolution of gas that signals the duration of the hydrolysis of the carbodiimide. 

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