Carbodiimides reaction with, phosgene

Cyclic carbodiimides also undergo a rapid reaction with phosgene in methylenechloride to form the expected adducts 55, which on hydrolysis give cyclic allophanoyl chlorides 56.22... 

Isothioureas can be prepared on insoluble supports by S-alkylation or S-arylation of thioureas (Entry 7, Table 14.6). Further methods for the preparation of isothioureas on insoluble supports include the N-alkylation of polystyrene-bound, A/,/V -di(alkoxy-carbonyl)isothioureas with aliphatic alcohols by Mitsunobu reaction (Entry 7, Table 14.6) and the addition of thiols to resin-bound carbodiimides [7]. Resin-bound dithio-carbamates, which can easily be prepared from Merrifield resin, carbon disulfide, and amines [76], react with phosgene to yield chlorothioformamidines, which can be converted into isothioureas by treatment with amines (Entry 8, Table 14.6). The conversion of support-bound a-amino acids into thioureas can be accompanied by the release of thiohydantoins into solution (see Section 15.9). The rate of this cyclization depends, however, on the type of linker used and on the nucleophilicity of the intermediate thiourea. 

The reaction of N,N -disubstituted thioureas 15 with phosgene (carbonyl chloride) affords aliphatic and aromatic carbodiimides 16 in good yields. For example, addition of phosgene... 

In peptide chemistry two methods are used frequently. The reaction of phosgene with protected amino acids leads to symmetric anhydrides (equation 4), after disproportionation and release of carbon dioxide, which can be readily used to build up a growing peptide chain. - More recently, symmetrical amino acid anhydrides have been generated by carbodiimides like water soluble carbodiimide and... 

Using this method, the complex [Fe(cp)(CO) j C(0)NHMe ] has been converted into [Fe(cp)(CO) j(CNMe)]Cl, and cis-[Pt(PPh3)j C(0)NHMe Cl] has been used to prepare cj s-[Pt(PPh3)(CNMe)CIj] [635]. In an interesting variation on this procedure, the reaction of phosgene with unsymmetrical carbodiimide adducts of iron has been used to prepare iron(II) complexes containing two different isonitrile ligands at a now chiral centre [636] ... 

Dithiocarbamic salts are suitable starting materials for the preparation of isothiocyanic esters (mustard oils), their reactions with heavy-metal salts,771 chloroformic esters,772 phosgene,768 carbodiimides,805 phosphorus oxychloride,806 aryl cyanates,732 or sodium hypochlorite807 usually giving good yields. Reaction of amines 808,809 or their hydrochlorides with thiophosgene810 is also generally applicable. 

Primary cycloaliphatic amines react with phosgene to form isocyanates. Reaction of isocyanates with primary and secondary amines forms ureas. Dehydration of ureas or dehydrosulfiirization of thioureas results in carbodiimides. The nudeophihcity that determines rapid amine reactivity with acid chlorides and isocyanates also promotes epoxide ting opening to form hydroxyalkji- and dihydroxyalkjiamines. Michael addition to acrylonitrQe yields stable cyanoethylcycloalkylamines. 

Indole-1-carboxylic acid can be converted by treatment with a carbodiimide to the anhydride (413), which can undergo reaction with amines or the sodium salts of phenols, thiophenols, pyrroles, and indoles. For example, it reacts with the sodium salt of pyrrole-2-carbaldehyde to give the product (414) (Scheme 143) <87JOC3934>. V-Chloroformylcarbazole (415), prepared by the reaction of carbazole with phosgene, has been used effectively for the fluorogenic labeling of amino acids (Equation (118)) <90TL1455>. 

Acidic reagents seem to offer milder conditions. Dehydration reactions forming cyanides can be performed with phosgene [1049-1052], diphosgene [1053-1055], triphosgene [1056], phenyl chloroformate [1057], oxalyl chloride [1058, 1059], tri-chloroacetyl chloride [1060-1062], acetic anhydride [1063-1074], TFAA [1075-1082], phosphorus oxides [1083-1088], phosphorus oxychloride [1089-1098], phosphorus pentachloride [1099], triphenylphosphine/haloalkanes [1100-1103], thionyl chloride [1104-1118], p-tosyl chloride [1119-1124], triflic anhydride [1125-1127], chlorosulfonyl isocyanate [1128], the Burgess reagent [1129], phenyl chloro-thionoformate [1130], cyanuric chloride [1131-1134], carbodiimides [1135, 1136], CDC [1137], PyBOP [1138], AlCU/Nal [1139], and acetonitrile/aldehyde [1140], and by pyrolysis [1141]. 

The above processes are only selected examples of a vast number of process options. In the case of carbonylation, the formation of by-products, primarily isocyanate oligomers, allophanates, and carbodiimides, is difficult to control and is found to greatly reduce the yield of the desired isocyanate. Thus a number of nonphosgene processes have been extensively evaluated in pilot-plant operations, but none have been scaled up to commercial production of diisocyanates primarily due to process economics with respect to the existing amine—phosgene route. Key factors preventing large-scale commercialization include the overall reaction rates and the problems associated with catalyst recovery and recycle. 

Carbonyl dichloride (phosgene) phosphoryl chloride/ phosphorus trichloride thiophosgene, thionyl chloride/ sulfur dichloride and cyanuric chloride react with carbodiimides to give the expected chloroformamidine derivatives. In the reaction of carbodiimides with two equivalents of carbonyl chloride N,N -disubstituted chloroformamidine N-carbonyl chlorides 703 are obtained. 

Homophthalic anhydrides can be prepared by the dehydration of homoph-thalic acid with add chloride, acid anhydride, phosgene, thionyl chloride, benzene sulfonyl chloride, ketene, phosphorous pentoxide, dicyclohexyl-carbodiimide, or J -carbonyldiimidazole. However, these methods are not always effective for the acid-sensitive and/or unreactive homophthaUc acid derivatives. We developed a very mild and efficient method for obtaining homophthaUc anhydrides using (trimethylsilyl)ethoxyacetylene [9] (Scheme 1). Thus the treatment of homophthaUc acid 1 with (trimethylsi-lyl)ethoxyacetylene 2 in inert solvents such as methylene chloride, 1,2-di-chloroethane, and acetonitrile gave the homophthaUc anhydride 3 in a quantitative yield accompanied by ethyl trimethylsilyl acetate as the only side product. The high purity homophthaUc anhydride 3 could be obtained for the next cycloaddition reaction just by evaporation to remove the reaction solvent and the formed ethyl trimethylsilyl acetate. The method is quite useful, and was also applicable to the syntheses of hetero-homophthalic anhydrides 4. 

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