3-acyl-1,5-benzodiazepines in the reactions of 5,5-dimethyl-2-formylcyclohexane-1,3-dione with certain 1,2-diaminobenzenes

Abstract

Continuing our study of the synthesis of 3-acyl-l,5-diazepines through reaction of 2-acyicyclane-l,3diones with 1,2-diamines [I, 2] we have examined the reaction of 2-formyl-5,5-dimethylcyclohexane-l,3-diones (I) with 4-methyl-(lib), 4-benzoyi-(IIc), and 1,2-diamino-4-nitrobenzenes (IId). As shown in [2], the formylcyclanedione I and o-phenylenediamine (IIa) react in a molar ratio of 1 : 1 to give enamine IIIa. The presence of two non-equivalent amino groups in the starting diamines IIb-d makes the possible formation of two isomers in these reactions.Under experimental conditions for similar reactions (mixing of hot ethanolic solutions of the starting materials and subsequent recrystallization of the obtained product) only in the reaction of diamine lid is a single isomer formed and this is 2-(2-amino-5-nitrophenylaminomethylene)-5,5-dimethylcyclohexane-l,3-dione (IIId). In the case of diamines lib,c, a mixture is formed consisting of the main product which is enamine IIIb or IIIc and also the product of reaction at the second amino group, i.e., 2-(2-amino-5-methylphenylaminomethylene)-5,5dimethylcyclohexane-l,3-dione and 2-(2-amino-4-benzoylphenylaminomethylene)-5,5-dimethyicyclohexane-l,3dione respectively. The pure isomers IIIb,c could be prepared by treating formylcyclanedione I with diamines IIb,c at -20~ and precipitation of the products by aqueous potassium chloride solution.The structure of the obtained products was established through the analysis of spectral data. As has been shown in [1], in compounds of type III the most informative aspect of their PMR spectra is the chemical shift of the signal assigned to the aromatic proton situated in a meta position relative to the substituent (R or RZ). The shift of this signal depends on the way the amino groups in diamine II takes part in reaction with compound I. If the reacted amino group is situated meta to the substituent (R or R 1) the signal for this proton is shifted to high field relative to the signals of the other aromatic protons and is found in the region 6.84-6.86 ppm. In the opposite case, the signal is shifted to lower field (7.27 ppm) and does not differ significantly from those of the other aromatic protons. The observed shifts for the signals of compounds IIIc,d (6.79 and 6.80 ppm) unambiguously show that the

Efficient, environmentally benign, one-pot procedure for the synthesis of 1,5-benzodiazepine derivatives using N-methyl-2-pyrrolidonium hydrogen sulphate as an ionic liquid catalyst under solvent-free conditions

“…To highlight the advantages of this newly developed method, we have compared the results of the current study with those reported in literature for the same transformation using different conditions [20][21][22][23][24][25] (Table 1) When the reaction was carried out under solvent-free conditions at 60 °C, the product was isolated in 55% yield ( Table 2, entry 9). Furthermore, when the reaction was conducted in the presence of 0.14 g of the [H-NMP][HSO4] catalyst at 100 °C, the desired product 3e was isolated in a 85% yield ( The results of the optimization experiments indicated that the MCR was being catalyzed much more effectively by [H-NMP][HSO4] that any of the other catalysts tested, because the desired product was obtained in much higher yields over shorter reaction times when the reaction was conducted in the presence of this IL catalyst ( Table 2, entries 1-12).…”

“…For example, 1,5-dibenzodiazepine derivatives have been reported to exhibit inhibitory activities towards hepatitis C virus (HCV) NS5B [8] and HIV-1 protease [9,10], as well as finding numerous applications in medicinal chemistry [11], where they have been used as antiinflammatory [12], hypnotic [13], anticoagulant [14], antibacterial [15], antidepressant [16], antiepileptic [17,18] and analgesic [19] agents. Several methods have been reported for the synthesis of 1,5-benzodiazepine derivatives via the condensation of o-phenylenediamine and dimedone with various aldehydes or ketones in the presence of a wide variety of Brӧnsted acid catalysts, including acyl chlorides [8,9] oxalic acid in water [20], acetic acid in refluxing ethanol [21,22], HCl in ethanol [23], acetic acid in toluene [24] and H2SO4 in water [25]. Several other methods have also been developed for the synthesis of 1,5-benzodiazepine derivatives, such as the cycloaddition reaction of 2,2-dihydroxy-1-phenylethanone with an o-phenylenediamine derivative and dimedone [26], the hetero-Cope rearrangement and the condensation of a 2-formyl benzoic acid substrate with an o-phenylenediamine derivative and tetronic acid in water under microwave irradiation conditions [27].…”