Amines, reactions with carbodiimides

Reactions with Ammonia, Amines, Amine Derivatives and Azides. Ammonia, primary and secondary amines react with carbodiimides to give guanidine derivatives. For example, firom primary amines the guanidine derivative 559 is obtained. 

Polymers with pendant carbodiimide groups 27 are also synthesized from crossUnked polystyrene. In this synthetic route crossUnked polystyrene beads are chloromethylated and converted to the amines. Reaction with isopropyl isocyanate gives the corresponding ureas, which are treated with tosyl chloride and triethylamine to produce the crossUnked polycarbodiimides. This polymer is used in the polymer supported Moffatt oxidation of alcohols into aldehydes or ketones using benzene/DMSO. ... 

Reaction with carbodiimides 805 A primary aliphatic amine (0.1 mole) is added to a solution of dicyclohexylcarbodiimide (0.1 mole) and carbon disulfide (40 ml) in ether or tetrahydrofuran (100-200 ml) stirred at —10°. The temperature is allowed to rise to 20° during 3 h. The mixture is then set aside at room temperature for 12 h, after which the di-cyclohexylurea, is filtered off and washed with a little ether, the filtrate is evaporated, and the residual isothiocyanate is distilled in a vacuum or recrystallized. Yields are about 80%. 

Figure 15 Conjugation of a carboxylic add and an amine using the carbodiimide method. The carbodiimide activates the carboxyhc acid to speed up the reaction to the amine. Carbodiimides can be used with nonpolar or polar solvents, including water. Undesirable urea complexes may form as by-products. Details of the reaction are given in Table 3...

Figure 9 A synthetic mixture of water-soluble carboxylic acids separated by anion-exchange chromatography. Column 0.3 cm x 300 cm Diaoion CA 08, 16-20 p (Mitsubishi Kasei Kogyo). Eluant 200 mM HC1. Detection reaction with Fe3-benzohy-droxamic acid-dicyclohexy carbodiimide-hydroxylamine perchlorate-triethyl amine with absorbance at 536 nm. Analytes (1) aspartate, (2) gluconate, (3) glucuronate, (4) pyroglutamate, (5) lactate, (6) acetate, (7) tartrate, (8) malate, (9) citrate, (10) succinate, (11) isocitrate, (12) w-butyrate, (13) a-ketoglutarate. (Reprinted with permission from Kasai, Y., Tanimura, T., and Tamura, Z., Anal. Chem., 49, 655, 1977. 1977 Analytical Chemistry).

Figure 1.88 The maleimide group of BMPA reacts with a thiol-containing molecule to result in a modification having a terminal carboxylate group. Amine-containing molecules then can be conjugated to the carboxylate using a carbodiimide reaction with EDC.

Molecules containing phosphate groups, such as the 5 phosphate of oligonucleotides, also may be conjugated to amine-containing molecules by using a carbodiimide-mediated reaction (Chapter 27, Section 2.1). The carbodiimide activates the phosphate to an intermediate phosphate ester similar to its reaction with carboxylates (Chapter 3, Section 1). In the presence of an amine, the ester reacts to form a stable phosphoramidate bond (Reaction 13). 

Carboxylated silica particles may be coupled with amine-containing ligands, such as proteins, using a carbodiimide reaction with EDC. A similar protocol to that previously described for coupling to carboxylate polymer particles may be used. The following protocol is based on the method of Zhao et al. (2004), which was used for immobilizing monoclonal antibodies to E. coli 0157. 

Underivatized PE in liposomal membranes contains an amine group that can participate in the carbodiimide reaction with carboxylate groups on proteins or other molecules (Dunnick et al.,... 

Selenoureas are prepared by reaction of isoselenocyanates with amines, or by reaction of carbodiimides with a mixture of LiAlH4/Se and by reaction of cyanamides with LiAlH4/Se.267 272 The tyrosinase inhibitory activity and superoxide radical scavenger effect of selenoamides and selenoureas have been investigated (Scheme 84).273 275... 

A useful method for the synthesis of 5-chloro-l,2,4-thiadiazoles (206) is the reaction of amidines with trichloromethylsulfenyl chloride (see Equation (30)). 3-Halo derivatives (349) (X = Cl, Br, I) (Equation (57)) have been obtained in moderate yields from the corresponding amines (348) via the Sandmeyer-Gatterman reaction <84CHEC-I(6)463>. 3-Chloro-l,2,4-thiadiazolin-5-ones (350) and (351) can be prepared by reacting chlorocarbonylsulfenyl chloride with carbodiimides or cyanamides respectively (Scheme 79) <84CHEC-I(6)463>. 

Ethyl 5-aminopyrazole -carboxylates are converted into pyrazolo[3,4- / pyrimidines via condensation with Ph3P/Bt2 subsequent reaction with an arylazocyanate and further reacting two carbodiimide with amines. Yields ranged from 13 to 65% dependant on the substituent <2006MI1584, 2007BMCL2203>. A similar approach was used for synthesis of triazolo[4,5- / pyrimidine-7(6)ones from ethyl 4-aminothiazolo-5-carboxylates <2007MIxx>. 

Figure 220 AMCA may be linked to amine-containing molecules through its carboxylate group using a carbodiimide reaction with EDC.

Amine-reactive biotinylation reagents contain functional groups off biotin s valeric acid side chain that are able to form covalent bonds with primary amines in proteins and other molecules. Two basic types are commonly available NHS esters and car-boxylates. NHS esters spontaneously react with amines to form amide linkages (Chapter 2, Section 1.4). Carboxylate-containing biotin compounds can be coupled to amines via a carbodiimide-mediated reaction using EDC (Chapter 3, Section 1.1). 

---