The use of optically active O-alkyl ester hydrochlorides of L-phenylalanine and L-tyrosine as chiral micellar media for the catalysis of diels-alder reactions

Bull. Chem. Soc. Ethiop. 2017, 31(3), 509-518.  2017 Chemical Society of Ethiopia and The Authors DOI: http://dx.doi.org/10.4314/bcse.v31i3.15 ISSN 1011-3924 Printed in Ethiopia THE USE OF OPTICALLY ACTIVE O-ALKYL ESTER HYDROCHLORIDES OF LPHENYLALANINE AND L-TYROSINE AS CHIRAL MICELLAR MEDIA FOR THE CATALYSIS OF DIELS-ALDER REACTIONS P. Caumul*, P. Koonja, N. Namooya, A. Prayag, N. Joondan and S. Jhaumeer-Laulloo Department of Chemistry, Faculty of Science, University of Mauritius, Réduit, Mauritius (Received March 7, 2017; Revised December 15, 2017; Accepted December 18, 2017) ABSTRACT. The effect of a range of O-alkyl ester hydrochloride surfactants derived from L-phenylalanine and L-tyrosine as catalysts on the Diels-Alder reaction between cyclopentadiene and methyl acrylate was studied. Both chain lengths (C8-C14) and head groups of the surfactants were found to influence the yield and selectivity of the Diels-Alder product. The C10 derivatives of both phenylalanine and tyrosine surfactants gave the highest yields and selectivity. Phenylalanine ester hydrochlorides showed better catalytic activity than the tyrosine derivatives. Adduct optimum yield was obtained at a concentration relating to their critical micelle concentration (CMC) values. The Diels-Alder reaction was also found to be favored in acidic condition (pH 3) as well as in the presence of lithium chloride (LiCl) as salting out agent. KEY WORDS: Diels-Alder, Chiral catalysts, Phenylalanine, Tyrosine, Micelle, CMC INTRODUCTION The Diels-Alder reaction is one of the most important carbon-carbon bond forming reactions and has been involved in key steps in the making of important intermediates that leads to the synthesis of anti-cancer and anti-viral drugs such as Taxol and Tamiflu, respectively [1, 2]. Since then, Diels-Alder reactions have formed an important part of the synthetic repertoire of making intermolecular and intramolecular cyclic compounds. Different strategies of enhancing asymmetric Diels-Alder reactions have been reported [3, 4]. With this view, the choice of catalyst to enhance the yield and selectivity of Diels-Alder reactions has also been an important issue that needs to be addressed [5, 6]. Catalysts such as Lewis acids [7, 8] have been known to enhance Diels-Alder reactions but their use has been restricted since they decompose in the presence of a small amount of water and cannot be reused [9]. The use of surfactants in assisting a variety of organic reactions is highly promising for basic and applied research [10, 11]. Micelle forming surfactants have been widely used as reaction medium for many important organic reactions since micelles form organized assemblies that affect the rates of chemical reactions and the position of chemical equilibrium [12, 13]. The use of surfactants in micellar medium offers the possibilities for reaction control due to special properties such as solubilization, pre-orientation, microviscosity, polarity and charge effects that surfactants can confer [14]. These effects influence the organic reactions by affecting the yield, regio and stereochemistry of the products. The idea of micellization for the rate-enhancement of Diels-Alder reactions dates back to the 1980s, where higher yields were obtained when using water as solvent compared to other nonpolar solvents [15-18]. Hence, surfactants offer the possibility for organic reactions to occur in aqueous media, and from the viewpoint of green chemistry, water is safer, harmless and environmentally benign [19]. However, there has been limited work on the use of chiral micellar media to catalyze DielsAlder reactions. Amino acids are useful synthons from the chiral pool that help to provide a cost __________ *Corresponding author. E-mail: This work is licensed under the Creative Commons Attribution 4.0 International License 510 P. Caumul et al. effective way of synthesizing surfactants as chiral catalysts. Optically active surfactants derived from S-leucine and phenylalanine have been reported to be effective catalysts for the reaction between nonyl acrylate and cyclopentadiene [20]. In continuation for the search of effective chiral micellar catalysts for Diels-Alder reactions, a range of pre-synthesized ester hydrochloride surfactants derived from L-phenylalanine and Ltyrosine [21] were used as novel chiral micellar-based catalysts for the reaction between methyl acrylate and cyclopentadiene. The effect of chain length and head groups of the surfactants on the reaction yields and selectivity were investigated. The reaction conditions such as concentration of surfactants, temperature, time and solvent variation were also studied in view of investigating the optimum conditions for which these surfactants can act as effective catalysts for the Diels-Alder reaction. EXPERIMENTAL L-Phenylalanine was obtained from HiMedia Laboratories (India). L-Tyrosine, octan-1-ol, decan-1-ol, dodecan-1ol, tetradecan-1-ol, dicyclopentadiene and thionyl chloride were purchased from Sigma-Aldrich (USA). p-Toluene sulfonic acid (PTSA) was obtained from Merck (Germany). Silica gel (60–120 Mesh) used for column chromatography was obtained from Alpha Chemika (India). Cetyltrimethyl ammonium bromide (CTAB) was obtained from BDH Laboratory Supplies (England). Sodium dodecyl sulfate was obtained from Loba Chemie (India). 1 H and 13C NMR spectra were recorded at 250 MHz and 62.9 MHz, respectively, on a Bruker electro spin NMR spectrometer using CDCl3, D2O and DMSO-d6 as solvents. GC-MS analysis was carried out on a Clarus 500 GC-Clarus 560S Mass Spectrometer using an SGE BPX5 capillary column (30 m × 0.32 mm × 0.5 µm), helium gas as carrier with a flow rate of 1.50 mL/min, injector temperature of 240 oC, detector temperature of 270 oC and oven temperature program 100 oC (hold for 2 min), ramp rate of 15 oC/min to 280 oC (hold for 15 min), flow rate 1.50 mL/min. The cycloadduct isomers were identified by matching their mass spectra with those in the NIST library. The order of product retention time of the isomers was determined from literature data [22]. General method for the Diels-Alder reaction Cyclopentadiene was obtained by thermal cracking of dicyclopentadiene at 160 oC. Cyclopentadiene (0.32 mL, 3.80 mmol) and methyl acrylate (0.17 mL, 1.90 mmol) were added to an aqueous solution of the surfactant and the reaction mixture was stirred at room temperature for 72 hours. The mixture was extracted with diethylether (3 × 20 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and the excess solvent was removed under vacuo to yield the crude Diels-Alder adduct which was purified by column chromatography using hexane/ethyl acetate in a ratio of 2:1. The pure product was obtained in 95% yield and was analyzed using GC/MS. Methyl bicyclo [2.2.1] hept-5-ene-2-carboxylate. 1H NMR (CDCl3) δ (ppm): 1.23 (1H, m), 1.39 (2H, m), 1.84 (1H, m), 2.90 (2H, m), 3.61 (3H, s), 5.90 (1H, m), 6.15-6.19 (1H, m).13C NMR (CDCl3) δ (...truncated)