Dicyclohexylcarbodiimide , amide

FIGURE 27 13 The mechanism of amide bond formation by W W dicyclohexylcarbodiimide promoted condensation of a carboxylic acid and an amine... 

Dicyclohexylcarbodiimide is a solid material, the Lewis structure for which resembles that of ketene. The molecule is a widely used catalyst for amide synthesis and other dehydration reactions. 

A half-sandwich titanacarborane guanidinate complex is formed on treatment of the corresponding amide precursor with 1,3-dicyclohexylcarbodiimide (Scheme 106). The compounds have been employed as catalysts for the guanylation of amines (cf. Section V.C). ... 

Thus unsubstituted (R=H) and substituted (R = alkyl) non-stabilized diyiides 1 react with phenylisocyanate and dicyclohexylcarbodiimide (R NCX), leading to the formation of new monoylide type intermediates. These last ones react in situ with carbonyl compounds through a Wittig type reaction leading respectively to a,)8-unsaturated amides 2 and amidines 3, with a high E stereoselectivity, the double bond being di- or tri-substituted [48,49]. By a similar reactional pathway, diyiides also react with carbonic acid derivatives, with the synthesis as final products of -a,/l-unsaturated esters 4 and acids 5 [50]. 

The reaction of 5a-bromo-a-tocopherol (46) with amines was further elaborated into a procedure to use this compound as a protecting group Toe for amines and amino acids (Fig. 6.35).62 The protection effect was due to a steric blocking of the amino function by the bulky tocopheryl moiety rather than due to conversion into a non-nucleophilic amide derivative, and the Toc-protected amino acids were employed in the synthesis of dipeptides according to the dicyclohexylcarbodiimide (DCC) coupling method.64 The overall yield of the reaction sequence was reported to be largely dependent on the coupling reaction, since both installation and removal of the... 

Use of the relatively small cyclopropane ring drastically reduces the potential for deleterious steric bulk effects and adds only a relatively small lipophilic increment to the partition coefficient of the drug. One of the clever elements of the rolicyprine synthesis itself is the reaction of d,l tranylcypromine (67) with L-5-pyrrolidone-2-carboxylic acid (derived from glutamic acid) to form a highly crystalline diastereomeric salt, thereby effecting resolution. Addition of dicyclohexylcarbodiimide activates the carboxyl group to nucleophilic attack by the primary amine thus forming the amide rolicyprine (68). 

DV Kashelikar, C Ressler. An oxygen-18 study of the dehydration of asparagine amide by N,N -dicyclohexylcarbodiimide and p-toluenesulfonyl chloride. J Am Chem Soc 86, 2467, 1964. 

FIGURE 8.3 Synthesis of amides by aminolysis of unisolated activated esters obtained using carbodiimide by (A) ammonium hydroxide,12 (B) diaminomethane dihydrochloride neutralized with Et3N,15 and (C) the amine of crystalline salts of additives, R = H, Me, Et.13 DCC = dicyclohexylcarbodiimide HOBt = 1-hydroxybenzotriazole HONSu = A-hydroxysuccin-imide HONp = p-nitrophcnol HODhbt = 3-hydroxy-4-oxo-3,4-dihydrobenzotriazine. 

With the carboxylic acid 123, dicyclohexylcarbodiimide (DCC) mediated esterification and amidation reactions can be carried out (Scheme 4. 27) [113]. For example, the reaction of 123 with EtOH in the presence of DCC and IH-benzotriazol (BtOH) in bromobenzene with a catalytic amount of 4-(dimefhylamino)pyridine (DMAP)... 

Die Reaktion von Carbonsaure-amid-hydroximiden mit Carbodiimiden wurde am Beispiel der Umsetzung von Benzoesaure-amid-hydroximid mit Dicyclohexylcarbodiimid eingehend un-tersucht114. 

The ethynyl terminated imide oligomers are very attractive because their cured polymers are thermally stable (131). However, improvements are required in processability. An interesting approach to this problem was the synthesis and use of ethynyl-terminated isoimide (132). If the cyclodehydration of the amide acid intermediate is performed chemically with dicyclohexylcarbodiimide, isoimide is formed in almost quantitative yield. (Fig. 46). It is claimed that the isoimide provides better flow and solubility compared with the corresponding imide. At elevated temperatures, during cure, the isoimide rearranges into the... 

The most frequently used carboxyl derivatives in amide coupling are azides, RCO—N3, mixed anhydrides, RCO—O—COR, and esters of moderately acidic phenols, RCO—OAr (see Table 24-1). It also is possible to couple free acid with an amine group using a diimide, R—N=C=N—R, most frequently N,N -dicyclohexylcarbodiimide. 

Cyclization of N-alkyloxygly collie acid amides. These amides, e.g. 172 are readily obtainable from O-methylhydroxylamine and the appropriate acid with dicyclohexylcarbodiimide, and on refluxing in carbon tetrachloride with the same reagent, cyclization occurs to 173 [85ZN(B)398]. A similar cyclization is effected by thionyl chloride in the presence of l,l -thionyldiimidazole (86AP1084). 

Another in situ procedure for activating carboxylic acids utilizes earbodiimides, such as dicyclohexylcarbodiimide (DCC). DCC (19) plays an important role in peptide synthesis. Addition of a carboxylic acid to the C-N double bond leads to the activated species, an acyl isourea 20, which upon attack by a nucleophile (and alcohol or an amine) releases the corresponding ester or amide along with 21 (for the mechanism, see Chapter 5). However, in the conversion of 5 to 7 the DCC procedure gives poor results. 

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