Synthesis and Characterization of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4-Propoxybenzoates and Their Hydrochloride Salts

Abstract

Abstract:Five new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates were designed and synthesized as potential dual antihypertensive agents. The compounds were prepared as free bases and subsequently transformed to hydrochloride salts. The position of protonation of nitrogen atoms in the piperazine ring of hydrochloride salts was determined by means of 13 C-CP/MAS and 15 N-CP/MAS NMR and IR spectroscopy. Using these solid-state analytical techniques, it was found that both nitrogen atoms were protonated when excess hydrogen chloride was used for preparation of salts. On the other hand, when the equimolar amount of hydrogen chloride was used, piperazine nitrogen substituted by aryl was protonated.

Development of Pelubiprofen Tromethamine with Improved Gastrointestinal Safety and Absorption

“…The O–H bond in the PEL-T was confirmed at 3270 cm −1 , which was not observed for PEL. This intense O–H bond signal derives from the THAM absorption peak shift at 3346 and 3287 cm −1 [ 21 , 22 ]. In addition, the disappearance of the sharp peak of the O-H stretch at 2936 cm −1 in PEL and a strong asymmetric −COO − stretching vibration at 1670 cm −1 for the carboxyl salts in PEL-T were identified, showing a shift of the PEL absorption peak at 1729 cm −1 for the C=O stretch of a carboxylic acid group [ 23 ].…”

“…In addition, the disappearance of the sharp peak of the O-H stretch at 2936 cm −1 in PEL and a strong asymmetric −COO − stretching vibration at 1670 cm −1 for the carboxyl salts in PEL-T were identified, showing a shift of the PEL absorption peak at 1729 cm −1 for the C=O stretch of a carboxylic acid group [ 23 ]. Furthermore, a number of strong bands presented in the range of 3046–2000 cm −1 in the spectrum of PEL-T are expected to be generated from overtones of protonated amine groups and the combination of stretching vibrations, whereas the N-H stretching vibration in the THAM absorption peak was observed at 3400–3100 cm −1 [ 17 , 22 ]. Furthermore, the FT-IR spectrum of PEL-T showed additional IR bands at 1000 cm −1 , which corresponds to the C-O stretching vibrations, again confirming the presence of alcohol functional group of THAM moiety in the molecule.…”

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“…Chlorides of these acids formed by thionyl chloride treatment gave desired epoxides 7a–9a and 13a after reaction with 2,3-epoxypropan-1-ol [53]. In the last step final compounds 7–9 were prepared by a reaction of the epoxides with 1-(4-phenyl)piperazine and then converted to the hydrochloride salts using ethereal HCl to enhance their solubility in water [55]. …”

Synthesis and Determination of Physicochemical Properties of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4-Alkoxyethoxybenzoates

“…The hydrolysis was then performed by using a 2 M solution of sodium hydroxide and the desired acids 4 – 6 were obtained by displacing with HCl, extracting to chloroform and evaporating. The final products, hydrochloride salts 7a – c , 8a – c , 9a – c , were prepared according to the already published synthesis [24]. Briefly, the appropriate acids 1–3 were transformed into the potassium salt using potassium hydroxide in a mixture of methanol and propan-2-ol (ratio 1:3).…”

“…The obtained bases were finally converted to their dihydrochloride salts by extend of hydrochloric acid to enhance the solubility of the compounds in water. The protonation of the phenylpiperazine nitrogens was not experimentally determined for the discussed final compounds but the hypothesis is based on the measurement carried out for similar structures [24].…”