Synthesis and Pharmacological Activity of 4-Aryl-1,5-benzo[b]diazepine-2-carboxylic Acid Arylamides
It was reported that 1,5-benzodiazepine derivatives possess antiinflammatory [1] and analgesic [2, 3] activity. This study was aimed at developing pathways for the synthesis of 1,5-benzo[b]diazepine derivatives and characterization of their pharmacological activity. The traditional method of synthesis of 1,5-benzo[b]diazepine derivatives is based on the reaction of o-phenylenediamine with -dicarbonyl compounds. However, 4-aryl2,4-dioxobutanoic acids and their esters interact with o-phenylenediamine in inert solvents only with the formation of 3-phenacylidene-3,4-dihydro-2-quinoxalones [4 – 6]. According to [6], 4-aryl-2,4-dioxobutanoic acid arylamides (I) do not react with o-phenylenediamine in solvents but interact with this agent in the melt with the formation of both quinoxalones and 4-aryl-1,5-benzo[b]diazepin-2-carboxylic acid arylamides (II). Analogous dual reactivity of arylamides I was observed in [7]. The kinetics of reactrions between arylamides (I) and o-phenylenediamine with the formation of only 2-quinoxalones was studied in [8]. In this context, we have studied the reactions of arylamides Ia – If with o-phenylenediamine in aqueous ethanol solutions (see scheme) in a broad range of pH. It was established that these reactions (Method A) at pH 5.8 lead to the formation of the corresponding 4-aryl-1,5-benzo[b]diazepine-2-carboxylic acid arylamides (IIa – IIf) with yields from 82 to 90% (Table 1). The UV spectra of arylamides IIa – IIf exhbit intense bands with max = 260 – 270 nm (log = 4.75 – 4.90). The IR spectra of compounds IIa – IIf (Table 1) contain absorption bands due to NH groups in the region of 3311 – 3348 cm – , the bands of amide carbonyl groups in the region of 1682 – 1691 cm – , and (for compounds IIb, IId – IIf) the bands of ester carbonyls at 1710 – 1718 cm – . The H NMR spectra of compounds IIa, IIc – IIf (Table 1) display the signals from protons of methylene groups at = 3.69 and 3.82 ppm), representing singlets broadened due to inversion of the seven-member cycle. This inversion is analogous to that observed for 1,4-benzodiazepines [9] and 4-methyl-1,2-dihydro-3H-1,5-benzodiazepin-2-one [10]. The presence of an electron-acceptor substituted in ortho position of aromatic ring of the amide fragment (compound IIe) leads to a shift of the amide proton singlet by 2.10 – 2.16 ppm to weaker fields as compared to the case of para-substituted amides (IId, IIf). In contrast to the data of [7], our syntheses using method A showed no influence of the character of substituents in the aroyl or arylamide fragments on the yield of compounds II. It should be noted that the synthesis of benzo [b]diazepines by method A requires strict observation of the time schedule, since an increase in the reaction time leads to accumulation of 2-quinoxalone derivatives in the reaction mixture. Compounds IId and IIf were also obtained via interaction of the corresponding arylamides, Id and If, with o-phenylene-bis-triphenylphosphinimine on heating in toluene (method B). The product yields in this case are reduced to 15 and 27% yields, respectively, because the process of isolation and purification of the target compounds is accompanied by the formation of 2-quinoxalones.
The 1,4-addition of singlet oxygen to 2,6-dimethoxy-1-(2-methoxyethenyl) benzene and 2-methoxy-1-(2-methoxyethenyl)naphthalene. The 1,4-endoperoxides as equivalents of 6-oxo-2,4-cyclohexadienylidenacetates.
Abstract The sensitized photooxygenation of vinylarenes 1 and 2 gave the corresponding 1,4-endoperoxides which were decomposed under mild conditions into quinone methides bearing ester function at the exocyclic carbon.
Design of a novel optical sensor for determination of trace gadolinium.
In this work, a highly selective and sensitive gadolinium (Gd) optical sensor based on immobilization of bis(thiophenal) pyridine-2,6-diamine (BPD), on a triacetylcellulose membrane has been reported. This optode exhibits a linear range of the Gd(III) ion concentration of 2.5 x 10(-6)M with a detection limit of 0.93 x 10(-8) M. Response time of the newly designed optode was within 1-2 min, depending on the Gd(III) ion concentration. Response of the sensor is independent of solution pH in the range of 2.0-9.0. It manifests advantages of: low detection limit, fast response time, and most significantly, very good selectivity with respect to a number of lanthanide ions (La, Ce, Sm, Tm, Ho, and Eu ions). The sensor was successfully regenerated with thiourea solutions and its response was reversible and reproducible (R.S.D. less than 1.4%). This optode was applied to determine Gd(III) in synthetic and water samples, and validated with certified reference materials (CRMs).