DBU as a catalyst for the synthesis of amides via aminolysis of methyl esters

Abstract

Benzoato de metila e p-clorofenil acetato de metila reagem com benzilamina e pirrolidina levando às correspondentes amidas. Estas reações são mais rápidas na presença de 20 mol% de DBU, fornecendo os produtos com rendimentos levemente superiores. Quando um diéster derivado do ácido L-aspártico foi usado como substrato, a reação com benzilamina e pirrolidina foi quimiosseletiva para o éster metílico, levando às correspondentes amidas em bons rendimentos. Reação do monoéster metílico do ácido aspártico com estas aminas conduziu a amidas com um grupo ácido livre em C1. Anilina, menos básica e menos nucleofílica, não formou os produtos esperados tanto na ausência quanto na presença de DBU. Através do monitoramento da reação por ESI-MS, foi possível interceptar os intermediários-chave catiônicos formados nas reações entre o benzoato de metila e o p-clorofenil acetato de metila com a benzilamina, os quais foram caracterizados por ESI-MS/MS.Methyl benzoate and methyl p-chlorophenyl acetate react with neat benzylamine and pyrrolidine to form the corresponding amides. These reactions are faster in the presence of 20 mol% of DBU providing slight better yields. When a diester derived from L-aspartic acid was used as substrate, the reaction with benzylamine and pyrrolidine in the presence of DBU was chemoselective and led to the corresponding amides in good yields. Reaction of aspartic acid monomethyl ester with these amines led to amides having a free carboxy group (at C1). Less nucleophilic and less basic aniline failed to form the expected products in both absence and presence of DBU. By monitoring the course of reaction by ESI-MS, key charged intermediates formed by the reactions of methyl benzoate and methyl p-chlorophenyl acetate with benzylamine were intercepted and further characterized by ESI-MS/MS. Keywords: DBU, catalysis, aminolysis, esters, amides, ESI-MS IntroductionThe amide is one of the most important functional groups in organic molecules. Life depends on this group and its properties since proteins and peptides are essentially polyamides. Many natural and synthetic bioactive molecules are also amides of low molecular weight.1 The preparation of amides from amines and carboxylic acids or its derivatives is therefore one of the most important and commonly employed reactions in organic synthesis. 1,2 Amides are usually prepared by transforming carboxylic acids into the corresponding acyl chlorides or by in situ activation of the carboxyl group followed by reaction of the resulting intermediates with amines.3 Aminolysis of esters has also been employed to form amides and has been considered as a model reaction to form peptide bonds. 2,4 In a molecular modelling study Schaefer III and co-workers 5 showed that the more stable pathway in the aminolysis of ethylformate by ammonia is a self catalyzed Lima et al. 2187 Vol. 22, No. 11, 2011 mechanism in which a second molecule of ammonia is involved in the transition state, facilitating the proton transfer process. The transition state (TS) for this pathway wa...

Weak functional group interactions revealed through metal-free active template rotaxane synthesis

“…of triethylamine (Et 3 N) led to the formation of rotaxane 4 in 68% yield after 1 h and 92% yield after 24 h. Under these conditions the ratio of rotaxane 4 to non-interlocked axle improved from 8:1 to 17:1 after 24 h, indicating that Et 3 N does not promote aminolysis of the building blocks in the absence of the crown ether. In contrast, the use of a stronger base, 1,8diazabicyclo[5.4.0]undec-7-ene (DBU), significantly reduced the formation of 4 (10% yield after 1 h) while increasing the amount of non-interlocked axle formed, suggesting that DBU accelerates the reaction of 2 and 3 at the expense of the active template reaction [46][47][48] . We next investigated the efficacy of rotaxane formation with less nucleophilic benzylic amines (Supplementary Table 2).…”

Light‐driven topochemical polymerization under organogel conditions of a symmetrical dipeptide–diacetylene system

“…The chemical structures of the functionalized peptide molecules reported in this work are presented in Scheme . Briefly, the ester 1 was first converted to 2 via a nucleophilic substitution with propargylamine in the presence of catalytic DBU . Then, the corresponding peptide‐DA conjugate 3 was prepared via the Ni‐catalyzed oxidative homo‐coupling reaction of terminal alkynes (Scheme ) .…”

Straightforward conversion of decoquinate into inexpensive tractable new derivatives with significant antimalarial activities

“…The proposed steps involve conversion of the ethyl ester into the less readily metabolized amide 24 27 attracts because of its economy. Although the reactions may be conducted with the neat reactants and reagents, the most expeditious involved the heating of DQ and excess of primary or secondary amine with DBU in a solvent.…”

“…Figure 2 below). Whilst this problem may be countered by the use of Lewis acidic reagents, 26 base-catalyzed aminolysis with an amine and 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU) 27 attracts because of its economy. Although the reactions may be conducted with the neat reactants and reagents, the most expeditious involved the heating of DQ and excess of primary or secondary amine with DBU in a solvent.…”