Synthesis and Antibacterial Evaluation of Some New Thiazole‐Based Polyheterocyclic Ring Systems

2‐Cyanoacetamido‐thiazole ( 1 ) was employed as a key for the construction of 6‐cyano‐7‐oxo‐7H‐thiazolo[3,2‐a]pyrimidine ( 4 ) which underwent reaction with hydrazine, malononitrile, ethyl cyanoacetate, and/or various 1,3‐bi‐nuclophilic reagents furnished the corresponding tri‐heterocyclic and tetra‐heterocyclic ring systems 5 – 12 . In addition, the reactions of 1 with various types of arylidene‐malononitriles and/or ethyl 3‐aryl‐2‐cyanoacrylates yielded the corresponding 1‐thiazolyl‐pyridine derivatives 16 and 20 , respectively. Furthermore, treatment of the precursor 1 with carbon disulfide and methyl iodide afforded the ketene dithioacetal derivative 21 which cyclized upon heating with hydrazine and/or 2‐aminobenzimidazole into the corresponding derivatives of N‐(thiazol‐2‐yl)‐1H‐pyrazole‐4‐carboxamide 22 and N‐(thiazol‐2‐yl)benzimidazo[1,2‐a]‐pyrimidine‐3‐carboxamide 23 . The antibacterial properties of these thiazole‐based heterocycles were examined against panel of two bacterial strains.     

Determination of metoprolol enantiomers in human plasma and saliva samples utilizing microextraction by packed sorbent and liquid chromatography–tandem mass spectrometry

A sensitive, accurate and reliable bioanalytical method for the enantioselective determination of metoprolol in plasma and saliva samples utilizing liquid chromatography–electrospray ionization tandem mass spectrometry was developed and validated. Human plasma and saliva samples were pretreated by microextraction by packed sorbent (MEPS) prior to analysis. A new MEPS syringe form with two inputs was used. Metoprolol enantiomers and internal standard pentycaine (IS) were eluted from MEPS sorbent using isopropanol after removal of matrix interferences using aliquots of 5% methanol in water. Complete separation of metoprolol enantiomers was achieved on a Cellulose‐SB column (150 × 4.6 mm, 5 μm) using isocratic elution with mobile phase 0.1% ammonium hydroxide in hexane–isopropanol (80:20, v/v) with a flow rate of 0.8 mL/min. A post‐column solvent‐assisted ionization was applied to enhance metoprolol ionization signal in positive mode monitoring (+ES) using 0.5% formic acid in isopropanol at a flow rate of 0.2 mL/min. The total chromatographic run time was 10 min for each injection. The detection of metoprolol in plasma and saliva samples was performed using triple quadrupole tandem mass spectrometer in +ES under the following mass transitions: m/z 268.08 → 72.09 for metoprolol and m/z 303.3 → 154.3 for IS. The linearity range was 2.5–500 ng/mL for both R‐ and S‐metoprolol in plasma and saliva. The limits of detection and quantitation for both enantiomers were 0.5 and 2.5 ng/mL respectively, in both matrices (plasma and saliva). The intra‐ and inter‐day precisions were presented in terms of RSD values for replicate analysis of quality control samples and were <5%; the accuracy of determinations varied from 96 to 99%. The method was able to determine the therapeutic levels of metoprolol enantiomers in both human plasma and saliva samples successfully, which can aid in therapeutic drug monitoring in clinical laboratories. Copyright © 2016 John Wiley & Sons, Ltd.     

Separation of fission produced 106Ru and 137Cs from aged uranium targets by sequential distillation and precipitation in nitrate media

Summary Ruthenium-106 and ¹³⁷Cs have been separated from thermal-neutron irradiated UO₃ targets aged for ~2.5 years by distillation and surface interactions in nitrate media of controlled chemical composition. After digestion of the aged targets with their aluminum wrapper in 2M NaOH solution, nitric acid was added to complete dissolution of the formed residue. The prepared fission product solution was separated from ¹²⁹I and 91.8% ¹⁰⁶Ru by sequential distillation from 20% and 40% HNO₃ solutions containing H₂O₂ and KMnO₄, as oxidants, and by boiling for 4 and 2.5 hours, respectively. The recovery yield of ¹⁰⁶Ru collected in 0.1M NaOH solution was ~68.2% with a radionuclidic purity of 399.99%. Thereafter, the fission product solution was brought to pH 9.5 by addition of NaOH solution to precipitate Al(OH)₃, MnO₂, and Na₂U₂O₇ which selectively retained the remaining fission products leaving, mainly, ¹³⁷Cs in the supernatant solution. The recovery yield of ¹³⁷Cs was ≥97.3% with ~99.75% radionuclidic purity. The gamma-ray emitter contaminants which could be detected and identified in the recovered ¹³⁷Cs solution, were ~0.25% ¹³⁴Cs and ~1.4 ^. 10^-3% ^152,155Eu.     

Selective Determination of Nicorandil with a Single Planar Solid-state Potentiometric Ion Selective Electrode

Novel screen-printed electrodes (SPEs) were constructed for the quantitation of nicorandil (NIC) in its pharmaceutical formulations. Different ion-exchangers and plasticizers were investigated, but the optimal potentiometric response was obtained using nicorandil-phosphotungstate (NIC-PTA) ion associate and tricresyl phosphate as a plasticizer. A Nernstian response of 58.80±1 mV/decade was obtained over a concentration range of (1×10⁻⁶–1×10⁻²) M with 1×10⁻⁵ M as a detection limit. Sensor morphology was characterized using scanning electron microscopy (SEM). The method was validated for the assay of NIC with high selectivity, accuracy (average recovery=100.54 %), and precision (%RSD≤2).     

Studies with polyfunctionally substituted heteroaromatics: A facile route for the synthesis of polyfunctionally substituted N-aminopyridines, 1,2,4-triazolo[1,5-a]pyridines and isoquinolines

The reactions of formaldehyde and acetaldehyde with active methylene compounds, followed by reaction with cyanoacetic acid hydrazide 2, afforded N-aminopyridine-2-one derivatives 5a-f. In contrast, the reactions of cyanoacetic acid hydrazide 2 with aliphatic aldehydes and cyanothioacetamide afforded pyridinethione derivatives 11a-b. Also, the reactions of active methylene compounds with formaldehyde and cyanoacetamide afforded pyridin(1H)-2-one derivatives 12a-c. The reactions of 5b with aldehydes and ketones afforded compounds 13a, b, 14, and 15, respectively. The reactions of 5b with arylidinemalononitriles 16a,b afforded isoquinoline derivatives 19a,b. Compound 19b by hydrolysis gave the final product 20. Compound 20 could also be formed by hydrolysis of 5b to give 21, followed by the reaction with 16b. © 1997 John Wiley & Sons, Inc.     

Studies with polyfunctionally substituted heteroaromatics: New routes for the synthesis of polyfunctionally substituted pyridines and 1,2,4-triazolo[1,5-a]pyridines

The 1-substituted ethylidenemalononitriles 1a–c condensed with triethyl orthoformate in refluxing acetic anhydride to yield the dienes 2a–c . On the other hand, a mixture of N,N-dimethylformamide and triethyl orthoformate condensed with 1a–d to yield the N,N-dimethylaminopentadienonitriles 2d–g . The pentadienonitriles 2d–g were also formed from the reaction of 1a–d with dimethylformamide dimethylacetal in refluxing acetic acid. When compounds 1a–c were treated with dimethylformamide dimethylacetal in refluxing p-xylene, a mixture of 3 , 4 and 2e–g was formed. The reaction of 2a , b with hydrazine hydrate afforded the N-amino-2-iminopyridines 5a , b . These were converted into the triazolo[1,5-a]pyridines 8a–d on treatment with benzoyl chloride and with dimethylformamide dimethylacetal. On the other hand, the reaction of 2c with hydrazine hydrate afforded the pyrazolo[3,4-b]pyridine 7c . Treatment of 2a , c or 2e , g with cyanoethanoic hydrazide afforded the N-(cyanoacetamido)pyridines 9a , b . The dienes 2d , f , g afforded the pyridones 11a–c on treatment with acetic acid and hydrochloric acid mixture. Compounds 11b , c were also formed on treatment of 2b , c with acetic acid hydrochloric acid mixture. The reaction of 2d , g with ethanolic sodium ethoxide gave the ethoxypyridines 13a , b .     

Functionally substituted alkylbenzotriazoles: Reactivity of alkylbenzotriazoles toward electrophilic and nucleophilic reagents

The reactivity of benzotriazolylacetone toward a variety of carbon and nitrogen electrophiles is reported. Several novel azolylbenzotriazoles as well as benzotriazolyl‐cinnolines have been synthesized. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:141–145, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10009