Kinetics of hydrolysis of 4-methoxy-2-[2-hydroxy-3(4-phenyl-1-piperazinyl)]propyl-2,3-dihydro-6-methyl-1,3-dioxo-1H-pyrrolo[3,4-c]pyridine in aqueous solutions.
The kinetics of hydrolysis of 4-methoxy-2-[2-hydroxy-3(4-phenyl-1-piperazinyl)]propyl-2,3-dihydro-6-methyl-1,3-dioxo-1H-pyrrolo[3,4-c]pyridine (I) in aqueous solutions at 333, 343, 353 and 363 K over the pH range 0.4-4.8 was investigated. The decomposition was observed with the HPLC method (LiChrosorb) 100 RP-18 column 250 x 4.0 mm ID, dp = 5 microm; mobile phase: acetonitrile--0.01 M phosphate buffer (H3PO4 + KH2PO4; pH 3) (50:50, v/v-phase A) or (30:70, v/v-phase B). The pH-rate profile indicated specific acid- and base-catalyzed reactions as well as spontaneous water-catalyzed decomposition of both dissociated and undissociated molecules of I. Various buffer substances exhibited general acid and base catalysis of the degradation. The ionic strength effect, the pKa value (4.2), the pHmin value (2.0) and thermodynamic parameters of the reaction (energy and enthalpy of activation and the frequency coefficient for the specific rate constants) were determined.
Muszalska
Izabela
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Department of Pharmaceutical Chemistry, Puznan University of Medical Sciences, Grunwaldzka 6, Poznań 60 780, Poland. imuszals@amp.edu.pl
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000378:metabolism*; D002021:Buffers; D002384:Catalysis; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007477:Ions; D015394:Molecular Structure; D011044:Poland; D011809:Quinones / Q000737:chemistry / Q000378:metabolism*; D012996:Solutions; D013696:Temperature; D013816:Thermodynamics
C478822:4-methoxy-2-(2-hydroxy-3-(4-phenyl-1-piperazinyl))propyl-2,3-dihydro-6-methyl-1,3-dioxo-1H-pyrrolo(3,4-c)pyridine; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002021:Buffers; D007477:Ions; D011809:Quinones; D012996:Solutions