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Lotfipour, Farideh ; Nematollahi, Davood ; Mohamadighader, Niloofar , et al. Green Synth. Catal.,2024. DOI: 10.1016/j.gresc.2024.10.007
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Abstract: This work is focused on the electrochemical late-stage modification of hydralazine (1-hydrazinylphthalazine) (HYD), a common antihypertensive drug, and the synthesis of its new sulfonylhydrazine derivatives. The synthesis of HYD derivatives has been easily accomplished in one-pot via electrochemical oxidation of HYD in the presence of arylsulfinic acid derivatives (ASA) in a water/ethanol mixture at constant current conditions. The electrochemical results show that anodically generated 1-diazenylphthalazine (HYDox) reacts with arylsulfinic acids and converts into the corresponding sulfonylhydrazine derivatives (SHD) with high yield and purity in an undivided cell equipped with graphite anode and stainless steel cathode. The main feature of this work is the synthesis of some new HYD derivatives in water/ethanol mixture as a “Green” reaction medium, using electrodes instead of toxic oxidants, having a high atom economy, having good energy efficiency and working at room temperature. These features are in accordance with the principles of green chemistry. Another advantage of this approach is that this method has led to the synthesis of sulfonylhydrazine derivatives in nano dimensions. Also, in this work, the electrochemical behavior of HYD and synthesized compounds (SHD) by different electrochemical methods were fully investigated and the results were reported. Furthermore, docking studies suggest that the products interact well with arylamine N-acetyltransferase (NAT) and show promising activity.
Keywords: Hydralazine ; Sulfonylhydrazine ; Late-stage modification ; Electrochemical synthesis ; Cyclic voltammetry ; Docking studies ; Nano-structured
Purchased from AmBeed: 824-80-6
CAS No. : | 824-80-6 | MDL No. : | MFCD03093775 |
Formula : | C6H4FNaO2S | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | VDDUCRSPMBZLMH-UHFFFAOYSA-M |
M.W : | 182.15 | Pubchem ID : | 23666220 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | General procedure: An oven-dried Schlenk tube equipped with a magnetic stir bar was charged with formamide 1 (2.0 mmol), KO-t-Bu (2.0 mmol) and CH3CN (2.0 mL). The mixture was stirred at 50 C for 30 min and then a CH3CN (2.0 mL) solution containing sodium sulfinates 2 (0.5 mmol) and NIS (1.0 mmol) was slowly added dropwise. The resulting solution stirred at 50 C for 12 h under air. The mixture was then cooled to room temperature, diluted with 30 mL of H2O, and extracted with EtOAc (3×20 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated under vacuum. The residue was purified by column chromatography on silica gel to give the products. |
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