Abbes Boukhari

Fadhel Ismail

Rafika Blida

Comptes Rendus Chimie

C. R. Chimie 13 (2010) 1440–1442Full paper/MémoireRegiospecific synthesis of 1,2-aminoalcohol by ring-opening of racemicstyrene oxide in presence of Lewis acidsAbbes Boukhari a,*, Rafika Blida a, Fadhel Ismail ba Department of Chemistry, Laboratory of synthesis and Biocatalysis Organic, University Badji-Mokhtar Annaba, Algeriab Department of Chemical and Process Engineering University Badji-Mokhtar Annaba, AlgeriaA R T I C L E I N F OArticle history:Received 27 March 2010Accepted after revision 9 July 2010Available online 15 September 2010Keywords:1,2-aminoalcoholsRegiospecificDiastereoisomerStyrene oxideSilicaLewis acidA B S T R A C TThe 1,2-aminoalcohol moiety is widely present in compounds possessing pharmaceuti-cally and biologically interesting properties During this work, we targeted the ringopening of the racemic styrene oxide by a chiral amine. In aqueous medium, a mixture ofdiastereoismers consisting largely of 2-N [1-phenylethyl] amino-1-phenylethanol 1 wasobtained. The use of silica in the reaction permits the formation of mixture ofdiastereoisomers, but, contrary to aqueous solution, the diastereoisomer 2-N [1-phenylethyl] amino-2- phenylethanol 2 was majority. On the other hand, the reactionof ring opening under acidic conditions led to a regiospecific compound, particularly in thepresence of Lewis acids, which only leads to the diastereoisomer 2. 2010 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.Contents lists available at ScienceDirectComptes Rendus Chimiewww.sc iencedi rec t .com1. IntroductionThe importance of vicinal amino alcohols as compoundspossessing pharmaceutical and biological properties iswell recognized. Indeed, the 1,2-aminoalcohol’s function ispresent in the widely consumed drug propanolol, a b-blocking agent and in the structure of serine proteaseinhibitors [1–3]. Optically active 1,2-aminoalcohols havean interesting role in asymmetric synthesis and are usefulas chiral ligands for catalysts or as chiral auxiliaries [4–5].Numerous synthetic methods exist for the preparation ofthese compounds [6–8]. Racemic epoxides, which areeasily available, can be readily transformed by reactionswith various nucleophiles into 1,2-substituted derivativesand especially into 1,2-amino alcohol [9]. In an ongoingproject in our laboratory; we were interested in thesynthesis of 1,2-aminoalcohols derivatives from reactionof (S)-a-methyl-benzyl-amine with racemic styrene oxidein presence of different solvents (Scheme 1). This* Corresponding author.E-mail address: boukhari_a2003@yahoo.fr (A. Boukhari).1631-0748/$ – see front matter  2010 Académie des sciences. Published by Edoi:10.1016/j.crci.2010.07.007enantioselective ring opening of epoxides by amines ismore attractive. The main objective of this work was toreport a short and practical sequence to obtain tworegioisomers after an attack of the (S)-a- methyl-benzyl-amine on the (R,S)-styrene oxide. In this article we willdescribe their synthesis and their characterizations.2. Results and discussion2.1. In aqueous mediumMost of the 1,2-aminoalcohols often have been derivedfrom natural compounds such as amino acids [10–11].Their structural motifs have proven a high efficiency inother asymmetric transformation. The method we used forthe synthesis of 1,2-Amino alcohols, involved the openingof the racemic styrene oxide by the (S)-benzyl-methyl-amine in water .We obtained two regioisomers (Scheme 1).The infrared spectra show the presence of an absorptionband around 3250–3500 cm1, which corresponds to thehydroxyl and amine groups.The analysis of 1H NMR and 13C NMR spectra revealedthe following characteristics.lsevier Masson SAS. All rights reserved.[(Scheme_1)TD$FIG]Scheme 1. Reaction of ring opening of racemic styrene oxide by (S)-methyl-benzylamine in aqueous medium.Table 11H NMR chemical shifts of methylene and methine of amino alcohols.Compound Group Chemical shift (ppm) SignalAmino alcohol 1 CH2NH 2.60–2.80 MCH-OH 4.70 DdAmino alcohols 2 CH2OH 3.55 MCH-NH 4.10 MTable 3Effects of different catalysts on the reaction yields.Catalyst Solvent 1 (%) 2 (%) Global yield (%)SiO2 CH2Cl2 19 81 60AlCl3 CH2Cl2 0 100 73ZnCl2 CH2Cl2 0 100 90[(Scheme_2)TD$FIG]Scheme 2. The mechanism for obtaining regioisomer 2 alone during theuse of a Lewis acid.A. Boukhari et al. / C. R. Chimie 13 (2010) 1440–1442 1441In the proton NMR, the distinction of 1,2-aminoalcohols 1/2 is observed easily by considering the protonchemical shift of H carried by the tertiary carbon C1. Thisproton is less shielded in the ethanolamine-1 (around4.70 ppm) than in the ethanolamine-2 (around 4.10 ppm)due to the proximity of oxygen (Table 1). For the samereasons, in regioisomers 1, the methylene protons (-CH2-)are significantly more shielded.The identification of regioisomers 1 and 2 is even easierby 13C NMR. Indeed, the tertiary carbon C1 is influencedeither a nitrogen or an oxygen and appears to 72 ppm and66 ppm for ethanol amines 1 and 2, respectively (Table 2).According to the 1H NMR spectrum of substitutedamino alcohol 1 whose data are given in Table 1 themultiplet (it should be in the form of a doublet of doubletsat higher resolution) of the methylene radical CH2-NHappears at 2.75 ppm. On the other hand, the 1H NMRspectrum of the isomer 2 shows that the methylene radicalCH2-OH appears at 3.55 ppm. This is probably due to thedifference in electronegativity of heteroatoms (N and O)situated at the immediate vicinity. For similar reasons, themethine proton of the CH-OH of amino alcohol 1and themethine proton of CH-NH the isomer 2, appear at 4.70 ppmand at 4.10 ppm, respectively.The identification of regioisomers 1 and 2 is even easierby 13C NMR. Indeed, the secondary carbon atoms areinfluenced by the presence of nitrogen and oxygen vicinalatoms. Their chemical shifts are presented in Table 2.Table 213 C NMR spectra of amino alcohols.Compound Group Chemical shift (ppm) SignalAmino alcohol 1 CH2-CH–OH 72.0 DCH2–NH - 54.8 TAmino alcohols 2 CH2–OH 54.7 TCH2-CH–NH- 66.0 D2.2. In acid mediumThe ONAKA’s method [12] was applied using silica inthe reaction medium. It was found that not only thepercentage of regioisomer 2 had increased but this isomerbecame majority comparatively to the aqueous mediumseen previously.The opening of the racemic epoxide in the presence ofsilica, which is considered as a slight acid had yieldedmajority the regioisomer 2. Thus Lewis acids that are acidsrelatively more strong should be interesting. Indeed, underthese last conditions a total absence of the regioisomer 1was noted. The experimental results are listed in Table 3.It is known that silica is sometimes used as Lewis acid inthe reactions of heterogeneous catalysis [13–14]. Indeed,the silicon atoms have a vacant 3d orbital willing to form adative bond with the oxygen atoms of carbonyl groups.Thus, the lone pair of oxygen of the oxide could interactwith a vacant 3d orbital of an atom of silicon from thesurface of silica gel. The breaking of bond O-C2 of theintermediate oxonium resulted after departure of the silicaat the corresponding ylide of oxamethine. The attack of theamine on the aliphatic carbocation leads to the aminoal-cohol 2 only. The mechanism is the same if one uses aLewis acid instead of silica (Scheme 2). The aminoalcohol 2derives from the nucleophilic attack of amine on carbon C2most hindered.3. ConclusionThe action of a primary chiral and aliphatic aminealways leads majority to the opening of the styrene oxideon the less hindered side with obtaining almost quantita-tive ethanolamine 1. The use of silica, in the reactionmedium, permits it to form mostly the other diastereo-isomer (compound 2). The reaction became regiospecific(obtaining a single regioisomer 2) when a Lewis acid isused in place of silica. The yield of the reaction forA. Boukhari et al. / C. R. Chimie 13 (2010) 1440–14421442obtaining the aminoalcohol 2 was evolved from a minorityin an aqueous medium to a majority state in the presenceof silica and to 100% in the case of Lewis acid (AlCl3 andZnCl2).4. Experimental4.1. General methodsMelting points were measured on a Kofler apparatus.Infrared spectra were recorded on a Shimadzu FTIR 8400 Sinstrument; the NMR spectra were measured on a BrukerAC 200 instrument in CDCl3 as solvent. Chemical shifts arein ppm from TMS as internal standard and couplingconstants are in hertz. Merck silica gel 60H was used toprepare short-column chromatography.4.2. Procedures for the preparation of 1,2-aminoalcohol4.2.1. In aqueous middleA mixture of 9.26 ml (72 mmol) of the (S)-methyl-benzyl-amine (dissolved in 5 ml of dichloromethane) and10 ml of water were added at 2.73 ml (24 mmol) of racemicstyrene oxide (dissolved in 5 ml of dichloromethane). Themixture was heated to reflux and stirred overnight. Afterextraction of the aqueous phase with twice 40 ml ofchloroform the organic phase was dried over sodiumsulphate. After evaporating solvent under reduced pres-sure and adding 50 ml of heptane to precipitate the solid,the product was separated, purified by recrystallizationand identified as the diastereoisomer 1 and the diastereo-isomer 2 is liquid.4.2.2. In presence of silicaAn equimolar quantity of racemic styrene oxide and(S)-methyl-benzyl amine (10 mmol) are mixed. It adds6 g of silica gel dissolved in 20 ml of dichloromethane.The suspension is stirred at reflux of solvent. Theevolution of the reaction is followed by TLC. At the endof the reaction (approximately 6 h), add 20 ml of distilledwater to the solution. The reaction mixture is returned toreflux for one hour to recover the organic productsadsorbed by the silica. After filtering the solid, the organicproducts are extracted two once 40 ml of dichloro-methane then purified by recrystallization in heptane andidentified as the diastereoisomer 1 and the diastereo-isomer 2 is liquid.4.2.3. In presence of Lewis acidsAn equimolar quantityof racemic styrene oxide and (S)-methyl-benzyl amine (10 mmol) are mixed. It adds 3equivalents of aluminum chloride dissolved in 20 ml ofdichloromethane. The suspension is stirred at reflux ofsolvent. The evolution of the reaction is followed by TLC.After filtering the solid, the organic products are extractedtwo once 40 ml of dichloromethane then purified byrecrystallization in heptane and identified only thediastereoisomer 2 as liquid.4.3. 2-N[1-phenylethyl] amino-1-phenylethanol 1This compound was obtained as a solid, mpt: 84–86 8C.IR (KBr, cm1): 3300; 1600; 1490; 1450; 1000, 960.1HNMR: (CDCl3, 250 MHz) 1.40 (d, J = 6.6 Hz, 3H), 2.60(dd, J = 6.8 Hz, 1H), 2.80 (dd, J = 6.8 Hz, 1H), 3.10 (s, 2H, OHand NH); 3.80 (q, J = 6.6 Hz, 1H), 4.70 (dd, J = 6.4 Hz, 1H),7.20–7.40 (m, 10H, aromatics).13C NMR: (CDCl3): 24.2 (q), 54.8(t); 57.7 (d); 72.0 (d);126.3(d); 127.5 (d); 128.2(d); 130.2(d); 144.1 (s); 146.8 (s).4.4. 2-N[1-phenylethyl] amino-2-phenylethanol 2This compound was obtained as oil.IR (Film): 3400; 1600; 1490.1HNMR: (CDCl3, 250 MHz) 1.30 (d, J = 6.6 Hz, 3H), 2.90(s, 2H, OH and NH); 3.55 (m, 2H), 3.80 (q, 1H), 4.10 (m, 1H),7.15–7.30 (m, 10H, aromatics).13C NMR: (CDCl3): 24.0 (q), 54.7(t); 61.5 (d); 66.0 (d);126.1(d); 127.2 (d); 128.0(d); 130.1(d); 141.0 (s); 145.0 (s).References[1] M. Genow, V. Dimitrov, V. Ivanova, Tetrahedron Asymmetry 22 (1997)3703.[2] Y. Hayashi, J.J. Rohde, E.J.J. Corey, Am. Chem. Soc. 118 (1996) 5502.[3] D.J. Ager, I. Prakash, D.R. Schaad, Chem. Rev. 96 (1996) 835.[4] A. Ganesan, C.H. Heathcock, Chemtracts Org. Chem. 1 (1988) 317.[5] C.A. Martin, K.B. Sharpless, Chemtracts Org. Chem. 1 (1988) 165.[6] A.G.M. Barrett, M.A. Seefeld, D.J.J. Williams, Chem. Soc. Chem. Commun(1994) 1053.[7] L.R. Krepski, K.M. Jensen, S.M. Heilmann, J.K. Rasmussen, Synthesis(1986) 301.[8] W.R. Jackson, H.A. Jacobs, B.R. Matthews, G.S. Jayatilake, TetrahedronLett. 31 (1990) 1447.[9] P. Barbaro, C. Bianchini, V. Sernau, Tetrahedron Asymmetry 7 (1996) 843.[10] T.V. RajanBabu, T.A. Ayers, G.A. Halliday, K.K. You, J.C. Calabrese, J. Org.Chem. 62 (1997) 6012.[11] T. Arantani, Y. Yoneyoshi, T. Nagase, Tetrahedron Lett. (1982) 685.[12] Y.M. Izumi, J. Onaka, Molecular Catalysis 74 (1992) 35.[13] K.C. Wilson, J.H. Pure, Appl. Chem. 72 (2000) 1313.[14] N. Besbes, H. Jellali, P. Pale, E.Srasra, M. L. Efrit C. R. Chimie 13 (2010) 358.

Regiospecific synthesis of 1,2-aminoalcohol by ring-opening of racemic styrene oxide in presence of Lewis acids

https://comptes-rendus.academie-sciences.fr/chimie/item/10.1016/j.crci.2010.07.007.pdf

Regiospecific synthesis of 1,2-aminoalcohol by ring-opening of racemic styrene oxide in presence of Lewis acids

Abstract

Similar works

Full text

Available Versions

Comptes Rendus Chimie