Syntheses from Amides

The Willgerodt reaction allows amide synthesis from aromatic aldehydes or ketones, using a secondary amine and a thiating agent. The mechanism of the more convenient Kindler modification, employing sulfur and morpholine, has been reviewed.281... 

The rates of nucleophilic addition to carbonyl groups that you met in Chapter 6 depend on the basicity of nucleophiles. As nitrogen bases are much stronger than oxygen bases (or, if you prefer, ammonium ions are much weaker acids than H3O ), amines are also much better nucleophiles than water or alcohols. This is dramatically illustrated in an amide synthesis from aniline and acetic anhydride in aqueous solution. 

Clearly, the partition of the unionized reagents between the two phases affects the extent of ionization of the acid and the amine and the equilibrium of amide synthesis from the nonionic forms of the reactants. Next we give the set of equations needed for calculating A biphasic ... 

Synthesis of amides from the coupling reactions of esters and amines is a potentially attractive method however, stoichiometric amounts of promoters or metal mediators are normally required [52], Complex 8 also catalyzes the amide synthesis from esters and amines and the reaction is general and efficient, and proceeds under neutral conditions, thus providing an environmentally benign method [15]. As demonstrated in the alcohol acylation process (Section 1.3.3, Table 1.6), when symmetrical esters are used, acylation of amines occurs by both acyl and alkoxo parts of the esters and they are incorporated in the products, and the only byproduct generated from this reaction is H2. 

Kang B, Fu Z, Hong SH (2013) Ruthenium-catalyzed redox-neutral and single-step amide synthesis from alcohol and nitrile with complete atom economy. J Am Chem Soc 135(32) 11704-11707... 

Scheme 1 Fatty amides synthesis from soybean oil...

Shimizu Kl, Ohshima K, Satsuma A (2009) Direct dehydrogoiative amide synthesis from alcohols and amines catalyzed by y-alumina supported silver cluster. Chem Eur J 15 9977... 

Nordstrpm LU, Vogt H, Madsen R (2008) Amide synthesis from alcohols and amines by the extrusion of dihydrogen. J Am Chem Soc 130 17672... 

Ghosh SC, Muthaiah S, Zhang Y, Xu X, Hruig SH (2009) Direct amide synthesis from alcohols and amines by phosphine-ftee ruthenium catalyst systems. Adv Synth Catal 351 2643... 

Ghosh SC, Hong SH (2010) Simple RuCl3-catalyzed amide synthesis from alcohols and amines. Eur J Org Chem 4266... 

Dam JH, Osztrovszky G, Nordstrpm LU, Madsen R (2010) Amide synthesis from alcohols and amines catalyzed by ruthenium V-heterocyclic carbene complexes. Chem Eur J 16 6820... 

Muthaiah S, Ghosh SC, Jee JE, Chen C, Zhang J, Hong SH (2010) Direct amides synthesis from either alcohols or aldehydes with amines activity of Ru(II) hydride and Ru(0) complexes. J Org Chem 75 3002... 

Chen C, Zhang Y, Hongs H (2011) V-heterocyclic carbene based ruthenium-catalyzed direct amide synthesis from alcohols and secondary amines involvement of esters. J Org Chem... 

Cook, G.R. (2005) Amides synthesis from amines by carbonylation. Science of Synthesis, 21, 114—130. 

Moreover, they also developed a transition-metal-ftee system for amides synthesis from styrenes using ammonia as nitrogen source [24] (Scheme 3.6). The amount of 10.8 equivalents of TBHP was necessary for this transformation. Various primary aryl amides were obtained in moderate to good yields (25-81 %). Benzaldehydes should be the key intermediates which are generated from styrenes via C-C double bond cleavage under oxidation conditions. Finally, the intermediates reacted with ammonia to give the desired amides. 

Scheme 3.9 The proposed mechanism for primary amides synthesis from terminal afkynes with aqueous ammonia...

Table 3.1 Amide synthesis from alcohols and aldehydes using ammonia as nitrogen source...

Scheme 3.19 Amides synthesis from secondary alcohols using trimethylsilyl azide as a nitrogen...

Scheme 3.27 Mn02-promoted amides synthesis from methylarenes...

Soule J-F, Miyamura H, Kobayashi S (2011) Powerful amide synthesis from alcohols and amines under aerobic conditions catalyzed by gold or gold/iron, -nickel or -cobalt nanoparticles. J Am Chem Soc 133(46) 18550-18553... 

Nie R, Shi J, Xia S, Shen L, Chen P, Hou Z, Xiao F-S (2012) Mn02/giaphene oxide a highly active catalyst for amide synthesis from alcohols and ammonia in aqueous media. J Mater Chem 22(35) 18115-18118... 

Scheme 40 Weinreb amide synthesis from backbone amide linker (BAL)...

In 2007, Milstein reported an approach for the transition metal catalysed intermolecular formation of amides from alcohols and amines in the absence of a hydrogen acceptor (Scheme 12.19). In contrast with conventional amide synthesis from activated carboxylic acid derivatives which produces chemical waste, this environmentally benign approach produces hydrogen gas as the only byproduct. The catalyst used for this reaction is a dearomatised Ru(PNN)pincer complex which serves as a bifunctional catalyst. The ligands, as well as the metal centre, play a role in bond making or bond breaking steps of the catalytic cycle. 

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