Amides from alcohols and amines

The first example of the ruthenium-catalyzed synthesis of amides from alcohols and amines was reported by Murahashi et al. in 1991 [82aj. The contrast results were obtained from the RuH2(PPh3)4-catalyzed reaction of 5-aminopentanol. Thus, piperidine was obtained in 79% yield, while similar treatment in the presence of a hydrogen acceptor of l-phenyl-l-buten-3-one gave piperidone in 65% yield (Eq. (7.36)). Recently, Williams reported the intermolecular amidation reaction of benzyl alcohols with amines in the presence of [Ru(p-cymene)Cl2]2 and 3-methyl-2-butanone [82bj. 

Scheme 21 Acceptorless-protocol to generate secondary amides from alcohols and amines...

Gunanathan C, Ben-David Y, Milstein D (2007) Direct synthesis of amides from alcohols and amines with liberation of H2. Science 317 790... 

Cho D, Ko KC, Lee JY (2013) Catalytic mechanism for the ruthenium-complex-catalyzed synthesis of amides from alcohols and amines a DFT study. Organometallics 32 4571... 

Soule J-F, Miyamura H, Kobayashi S (2013) Direct amidation from alcohols and amines through a tandem oxidation process eatalyzed by heterogeneous-polymer-incarcerated gold nanopartieles under aerobic conditions. Chem Asian J 8(ll) 2614—2626... 

Direct Synthesis of Amides from Alcohols and Amines.60... 

Fig. 5 Possible catalytic cycle for the direct synthesis of amides from alcohols and amines, catalyzed by the PNN ruthenium pincer complex 5...

As mentioned above, hydrogen atoms, removed from the alcohol substrate, can return to form the product however, if the final hydrogenation step could not occur, a product that is more oxidized than the starting material is obtained. The formation of esters from alcohols and of amides from alcohols and amines concern the most representative and studied reactions of this type. In these cases, aldehydes, formed on the first oxidation stage from alcohols, undergo Tishchenko- and Cannizzaro-type reactions, where esters or carboxylates and alcohols are formed upon fusion or disproportionation of aldehydes, respectively. 

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. 

The mechanism of formation of amide from alcohol and amine catalysed by a Ru-NHC complex (Scheme 4) has been thoroughly explored by joint experimental and theoretical studies." It proceeds through oxidation of the alcohol to an aldehyde followed by addition of the amine to give a ruthenium-complexed hemiaminal, which is further oxidized to form the amide and regenerate the catalytic species. 

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... 

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... 

Tertiary amides derived from pyrrole, indole and carbazole were hydro-genolyzed to alcohols and amines by refluxing in ether with a 75% excess (0.88 mol) of lithiwn aluminum hydride. Benzoyl derivatives of the above heterocycles afforded 80-92.5% yields of benzyl alcohol and 86-90% yields of the amines [7704]. 

The dicarbonyl [12539-66-1] available from 1,10-(N2)2B10H8 is another important species because of the scope ofits chemistry. Carbonyls of P 12 -12] can be formed from CO and the conjugate acid of [B12H12]2 . The B10- and B12-carbonyls exhibit very similar reactivity (99). The carbonyls can be considered anhydrides of carboxylic acids and accordingly react with alcohols and amines-to give esters and amides ... 

Both Siegel et al. (122) and Lawrence et al. (123) have described automated systems for the purification of small arrays of amines and amides. A 48-member array of P-amino alcohols prepared from epoxides and amines was purified using SPE by Shuker et al. (124). Blackburn et al. (125) have described the purification of a 60-member 3-aminoimidazo[l,2-fl]pyridine array obtained from a multiple-component condensation, and Bussolari et al. (126) purified a small array of phenylpropyl amines obtained from dihydrocoumarins and amines. A few applications where ion-exchange resins have been substituted with other solid phases have also recently appeared. For example, the purification of several carbohydrate arrays tagged as hydrophobic O-laurates using Ci8 silica producing up to 10-30 mg of >90% pure individuals was described by Nilsson et al. (127), and Curran et al. purified fluorous-... 

Cyanuric chloride has been used for the preparation of acyl chlorides, amides, and peptides. Conversion of cyanuric chloride into 2-chloro-4,6-dimethoxy-l,3,5-triazine (CDMT, 6) leads to a reagent that upon reaction with carboxylic acids produces the highly reactive 2-acyloxy-4,6-dimethoxy-l,3,5-triazines.P l The resulting active ester is a powerful acylating agent for alcohols and amines. The activation is performed in presence of a base, preferentially NMM, which leads to intermediate formation of 4-(4,6-dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM, 7)P l (Scheme 5). This addition product is readily prepared from the commercially available CDMT (6) and NMM in THF and can be stored as solid compound in the cold.P P l It offers the advantage that it can be used in a one-... 

Apart from lubricants, spin finishes contain antistatic and spreading and emulsifying agents. These are generally alkyl sulfates, alkylbenzene sulfonates, sulfonated fats and oils and poly(ethylene glycol)-modified fatty acids, fatty acid amides, fatty alcohols, and fatty amines. Potassium alkyl phosphates are extensively used in the production of polyester staple fibers. 

Isomerizations. A convenient method for the conversion of alkynes to conjugated dienes is by treatment with Ph P. The synthetic application is shown in the preparation of 2,4-alkadienols from 2-alkynoic acids involving esterification with pentafluorophenol, isomerization with PhjP (PhMe, 50°), and reduction with DIBAL-H. Even propargyl bromide can be isomerized to give 1-bromopropadiene, albeit in 29% yield. Conjugated alkadienoic esters and amides are obtained in one step from the pentafluorophenyl alkynoates on reaction with alcohols and amines, respectively, after treatment with catalytic amount of PhjP. 

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