Synthesis and characterization of unsaturated diacyl and alkyl-acyl piperazinederivatives

Sait Sari,Seda Ünalan,Mehmet Yilmaz

doi:10.3906/kim-1907-16

Abstract

The aim of this study is to obtain new unsaturated piperazine compounds by the reactions of piperazine (1a) and piperazine derivatives (1b-1d) with acylation reactive groups (a-2j). Methacryloyl piperazine (1b) was synthesized from the reaction of methacrylic anhydride with piperazine (1a). Acyl chlorides (2b-2d) were prepared from the reaction of thionyl chloride with carboxylic acids (3a-3c) obtained as a result of the reaction with malonic acid and suitable aldehyde (5-methylfuran-2-carbaldehyde for 3a, cinnamaldehyde for 3b, and thiophene-2-carbaldehyde for 3c), respectively, by literature methods. Acyl chlorides 2ed and 2f }were obtained from the reaction of commercially purchased carboxylic acids 3d and 3e with thionyl chloride. Acyl chlorides (2g-2j) were synthesized from the reaction of thionyl chloride with carboxylic acids (3d-3g) transformed from hydrolyzation of esters (4a-4d}) obtained as a result of the reaction of triethyl phosphonoacetate with a suitable ketone (acetophenone for 4a, benzophenone for 4b, 1-(5-methylfuran-2-yl)ethan-1-one for 4c, and 1-(thiophen-2-yl)ethan-1-one for 4d), respectively, by literature methods. Unsaturated piperazine derivatives 5a and 5b were obtained from the reaction of 1bwith 2b and 2e, respectively. In addition, from the reaction of 1b and acyl chlorides (2b-2j), unsaturated piperazines (5c-5k) were synthesized in medium to good yields (63%-84%). Also, 5l-5g-and 5r-5w were obtained from the reaction of allyl piperazine (2c) and cinnamyl piperazine (2d) with acyl chlorides (2a-2f).

Highlights

Heterocycles are organic molecules that have great importance both biologically and industrially
In medicinal chemistry the piperazine scaffold is considered a privileged structure for its capability of binding to multiple receptors with high affinity [6] and it can be found in drugs such as imatinib [7], sildenafil [8], indinavir [9], and gatifloxacin [10] (Figure 1)
5f, 81 a) Isolated yields are based on piperazine derivative (1a or 1b)

Summary

Introduction

Heterocycles are organic molecules that have great importance both biologically and industrially. Piperazine compounds 5l (63%) and 5m (70%) were obtained from the reaction of 1c with 2b and 2d, respectively. Treatments of 1c with 2f and 2a gave piperazine derivatives 5n (90%) and 5o (76%) in high yields, respectively.

Objectives

Results

Conclusion