Amides, with alcohols

EXTENSIONS AND COMMENTARY N-Methyltryptamine (monomethyltryptamine, NMT) is an alkaloid that has been found in the bark, shoots and leaves of several species of Virola, Acacia and Mimosa. However, the major snuffs associated with these plant have been shown to also contain 5-MeO-DMT and are discussed there. NMT has been synthesized in a number of ways. One can react 3-(2-bromoethyl)indole with methylamine. NMT can be isolated as the benzoyl derivative from the methylation of tryptamine with methyl iodide followed by reaction with benzoyl chloride, with the hydrolysis of this amide with alcoholic KOH. It can also be synthesized from indole with oxalyl chloride, with the resulting glyoxyl chloride reacting with methylamine in ether to give indol-3-yl N-methylglyoxalylamide (mp 223-224 °C from IPA) which is obtained in a 68% yield, which is reduced to NMT to give the amine hydrochloride (mp 175-177 °C from ) in a 75% yield. The most simple and direct synthesis is the formamide reduction given above. 

The carboxyl groups in the tricyclic compounds 211 (R or R = COOH), 386 (R = COOH) were transformed with thionyl chloride into chlorocar-bonyl groups, which were converted by amines to the amides, - - - with alcohols to the esters, - - and with hy-droxylamine to the hydroxamic acids. ... 

E. Reactions of Dialkylamides and Bis(trimethylsilyl)amides with Alcohols... 

JCS(D)1649] treatment of bismuth amides with alcohols or thiols gives the corresponding substituted products and secondary amines. 

The most common procedure for preparing bismuth alkoxides is the substitution reaction of bismuth halides with alkali metal alkoxides. The alternative is treatment of bismuth amides with alcohols. Bismuth alkoxides such as trimethoxide, triethoxide and triisopropoxide were first prepared in 80-93% yields by the reaction between BiCl3 and alkali metal alkoxides by Mehrotra et al. in 1966. Bismuth alkoxides are less soluble in organic solvents and the yields after purification by sublimation are generally very low (10-20%) [66IJC537]. Known aliphatic alkoxides include Bi(OEt)3... 

Ester and amide synthesis. Nicotinic anhydride activates carboxyhc acids (by forming mixed anhydrides) to be transformed into esters and amides, with alcohols and amines, respectively (catalytic DMAP). 

RfS02C1 reacted in a similar fashion with most nucleophiles, e.g. to give esters or amides with alcohols or secondary amines. However, in the reaction with a primary amine, such as C2H5NH2, the expected amide was not formed, but a chlorophilic reaction apparently occurred to give the salt RFS02 N + H3R as the sole product in many solvents, and a mixture of the sulfinate and the expected amide, e.g. RFS02NHC2H5 was formed in PO(OCH3)355. 

Summary of Reaction of Acid Chlorides, Anhydrides, Esters, and Amides with Alcohols... 

In addition to the homogeneous and heterogeneous TM catalysts discussed above, other catalysts/methods such as uano catalysts, carbon materials, enzymes, chiral catalysts and continuous flow techuiques have also been developed successfully and applied in /-alkylation reactions of amines/amides with alcohols. 

In 2015, Kobayashi and co-workers reported a PI/CB-Au/Pd (PI/CB, polymer-incarcerated metal nanoparticle catalyst with carbon black as a secondary supporter) complex-catalyzed IV-alkylatiou of amides with alcohols (Eq. 51) [169]. The catalyst could be reused 11 times without appreciable loss of catalytic activity (1st, 99 % lllh, 95 %). 

K-I Fujita, Komatsubara A, Yamaguchi R (2009) iV-alkylation of carbamates and amides with alcohols catalyzed by a Cp Ir complex. Tetrahedron 65(18) 3624-3628... 

Apsunde T, TrudeU M (2014) Solvent-ftee, base-free microwave-mediated iridium-catalyzed N-alkylation of amides with alcohols. Synthesis 46(02) 230-234... 

P Vinylplicnyl carbonyl forming Seiiiff bases with amine-templates) p-Vinylbcnzoic acid (Forming ester and amides with alcohol- and amine-ieniplatcs respectively) M>C... 

Simple palladium(II) salts such as chloride and acetate efficiently catalyse aerobic oxidative A-alkylation of amines and amides with alcohols. This method is suitable for a variety of sulfonamides, amides, aromatic and heteroaromatic amines as well as benzylic and heterobenzylic alcohols with a low loadings of the catalyst (0.5-1 mol%) and the alcohols. A selective carbon-carbon double bond assisted o-C-H olefination is catalysed by palladium(II) acetate. The terminal oxidant is oxygen. Addition of TFA is essential for any meaningful yield. (PdOCOCF3)+ has been proposed as the active catalyst. The observed large difference in the inter- and intra-molecular KIE values implied that the coordination of the C=C bond occurs before C-H palladation in the catalytic cycle consequently, a mechanism involving the initial coordination of allylic C=C bond to (PdOCOCF3)+ followed by selective o-C-H bond metalation has... 

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