A new route to α-hetero β-enamino esters using a mild and convenient solvent-free process assisted by focused microwave irradiation

A practical multi-step synthesis of ethyl N-functionalized $$\varvec{\upbeta }$$ β -amino benzimidazole acrylate derivatives as promising cytotoxic agents

“…As seen from the results in Table 2, we obtained a library of 16 new !-amino benzimidazole acrylate derivatives 12 in low yields (10-38%) for 12(b, c), 12(f-i), 12k and 12(m, n); in moderate yields (42-63%) for 12e, 12j and 12l, and in good yields (61-93%) for 12a, 12d and 12(o, p). of the identities of these compounds 12(a-p) were confirmed by 1 H, 13 C NMR and HRMS analyses. All the N-functionalized !-amino benzimidazole acrylates derivatives 12(a-p) adopted a characteristic (2E)-s-cis/trans conformation (Scheme 1), which is stabilized by an intramolecular hydrogen bond, as indicated by the strong downfield shifted resonance of the NH group on C-3 (12a, # NH = 11.78 ppm in 1 H NMR spectrum using DMSO-d 6 ).…”

“…This salt underwent facile heterocyclocondensation with commercially available ortho-phenylenediamine 3 in refluxed methylene chloride during 48 hours to give ethyl 2-(1H-benzimidazol-2-yl)acetate 4 (27% yield) [12]. Finally, the desired buildingblock 5 was easily prepared according to a previous method developed in our laboratory [13]. This solvent-free protocol consisted in reacting compound 4 with N,N-dimethylformamide diethyl acetal (DMF-DEA) at 90°C for 30 min.…”

“…under microwave irradiation conditions [14]. After purification by recrystallization from AcOEt (82% yield), the structure of ethyl 3-dimethylamino-2-(1Hbenzimidazol-2-yl)acrylate 5 was ascertained by HRMS, 1 H and 13 C NMR. Building-block 5 was prepared with an overall yield of 13% in multi-gram quantities.…”

“…With the hydrochloride salts of mono N-substituted diamines 11(a-p) in hand, our focus was the transformation of ethyl 3-dimethylamino-2-(1H-benzimidazol-2-yl)acrylate 5 into desired compounds 12 by transamination. Typically, the mechanism of this reaction is an additionelimination [18] after the loss of dimethylamine via an aminal intermediate, which could not be isolated [13]. In previous work, we used 5 as an ambident synthon in a regioselective azaannulation with isocyanate for the preparation of 1-oxo-1,2-dihydropyrimido[1,6-a]benzimidazole-4-carboxylates using solvent-free conditions under microwave irradiation [19].…”

Microwave Assisted Reactions in Organic Chemistry: A Review of Recent Advances

“…Some reactions under each of the above mentioned conditions are identified below. (Seijas et al, 1999;Dahmani et al, 1998) Aromatic nucleophilic substitutions are carried out using sodium phenoxide and 1,3,5-richlorotriazine under microwave irradiation.…”