Amines with carbodiimides

Illustrative examples of the acylation of support-bound amines with carbodiimides as coupling agents are listed in Table 13.3. Difficulties are usually encountered in the acylation of a-alkylamino acid derivatives (which are significantly less nucleophilic than simple secondary amines Entries 3 and 4) and Al-alkyl (Entries 5 and 6) or iV-aryl anilines. Acylations with haloacetic or related acids containing a leaving group prone to nucleophilic displacement should not be performed with the aid of HOBt and bases because O-alkylation of HOBt by the product occurs readily. 

Imines react similarly to amines with carbodiimides. ... 

Mechanism of amide formation by reaction of a carboxylic acid and an amine with dicyclohexyl-carbodiimide (DCC). 

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).

The general chemistry used in this approach involves the combination of a limited amount of an amine-terminated dendrimer core reagent with an excess of carboxylic acid terminated dendrimer shell reagent [31]. These two charge differentiated species are allowed to self-assemble into the electrostatically driven supramolecular core-shell tecto(dendrimer) architecture. After equilibration, covalent bond formation at these charge neutralized dendrimer contact sites is induced with carbodiimide reagents (Scheme 1). 

NL Benoiton, FMF Chen. Reaction of A-t-butoxycarbonylamino acid anhydrides with tertiary amines and carbodiimides. New precursors for 2-f-butoxyoxazol-5(4//)-one and IV-acylureas. J Chem Soc Chem Commun 1225, 1981. 

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>. 

Guanidines may also be formed by reaction of amines with carbodi-imides. This reaction is limited by the availability of carbodiimides, which are usually formed by several methods,24 including dehydration of ureas with the Edward Burgess reagent 11 (Scheme 9).25-27... 

Table 13.3. Acylation of support-bound amines with carboxylic acids and carbodiimides.

Table 13.4. Acylation of amines with support-bound carboxylic acids and carbodiimides.

The separation of this dicyclohexylurea urea is relatively laborious, that is, it has to be conducted by chromatography or crystallization. After the activation of carboxylic acid with carbodiimide B and subsequent acylation of a heteroatom nucleophile, one certainly obtains a urea as a side product, too. It has the structure C and thus is an amine, the separation of which can, however, be accomplished easily by extraction with aqueous hydrochloric acid. 

How an unsymmetrical urea can be prepared from a primary amine with a (diethyl-amino )propyl substituent (A) and ethyl isocyanate is illustrated using the example of compound C. This urea is the starting material for preparing a carbodiimide (see Figure 8.9), which activates carboxylic acids towards heteroatom nucleophiles. 

Dealkylation of tertiary amines with dibenzoyl peroxide, 44, 74 Decarboxylation, intermolecular, of isocyanates to carbodiimides, 43,32 Decker synthesis of amines, 44, 7t, 75 Dehalogenation of l,l,2-trichloro-2,3,3-trifluorocydobutane, 42,45 Dehydration, of formamides with phosphorus oxychloride to isocy-anides, 41, 13, 101 of 4- 2-hydroxyethyl)piperidine to quinuclidine, 44, 90 Dehydrohalogenation of 2-chloroallyl-amines to propargylamines, 44,55 Delepine reaction, to prepare 2-bromo-allylamine, 43, 6 Deoxyanisoin, 40,16 Deoxybenzoin, 40, IT Deoxypiperoin, 40, IT Deaylamine, 41, 8T... 

Dithiocarbamic acids 557, generated in situ from aliphatic amines and carbon disulfide, react with carbodiimides to give isothiocyanates 558 in 70-99 % yield. ... 

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. 

Half-sandwich lanthanide alkyl complexes and, subsequently oranolanthanide amides were found to be highly efficient catalysts for the cross-coupling reactions of carbodiimides with alkynes and amines, respectively [136, 137]. Although the half-sandwich lanthanide alkyl complexes can also catalyze the dimerization of alkynes, no homodimerization product is observed in the reaction of alkynes with carbodiimides. These reactions offer a wide scope for the substrates of terminal alkynes and amines, respectively [138]. 

C-Lithiations can be easily effected on A -1-protected 1,2,4-triazoles, the resulting 5-lithio derivatives being much more stable than C-hthiated 1,2,3-triazoles 5-Silylation can even be achieved using triethyl-amine with trimethylsilyl bromide - deprotonation of an iV -trimethylsilyl triazolium cation is presumably involved Exactly comparable silylations can be achieved with 2-aryl-l,3,4-oxa- and -thia-diazoles application of this regime to 1-phenyltetrazole produced phenyl trimethylsilyl carbodiimide in 90% yield ... 

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