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.
Untersuchungen über Schiffsche Basen, III: Thermische Valenzisomerisierung doppelter Schiffscher Basen von 1.2-Diaminen
Doppelte Aldimine von 1.2-Diamino-cyclopropanen gehen durch thermische Valenzisomerisierung in hervorragenden Ausbeuten in 2.3-Dihydro-1.4-diazepine uber. Versuche zur Valenzisomerisierung anderer doppelter Schiffscher Basen von 1.2-Diaminen werden mitgeteilt. — Uber Protonenresonanz-Untersuchungen zur Struktur der 2.3-Dihydro-1.4-diazepine, des 5.7-Dimethyl-2.3-benzo-1.4-diazepins und ihrer Kationen wird berichtet.