Efficient Regioselective Opening of Epoxides by Nucleophiles in Water under Simultaneous Ultrasound/Microwave Irradiation

Giovanni Palmisano; Silvia Tagliapietra; Alessandro Barge; Arianna Binello; Luisa Boffa; Giancarlo Cravotto

doi:10.1055/s-2007-984891

LETTER

Efficient Regioselective Opening of Epoxides by Nucleophiles in Water under Simultaneous Ultrasound/Microwave Irradiation

Giovanni Palmisano^a, Silvia Tagliapietra^b, Alessandro Barge^b, Arianna Binello^b, Luisa Boffa^b, Giancarlo Cravotto*^b
^a Dipartimento di Scienze Chimiche e Ambientali, Università degli Studi dell’Insubria, Via Valleggio 11, 22100 Como, Italy
^b Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via Giuria 9, 10235 Torino, Italy
Fax: +39(011)6707687; e-Mail: giancarlo.cravotto@unito.it;

Abstract

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Abstract

Epoxide cleavage by nucleophiles in aqueous media may suffer from competition by water itself, yielding the diol as byproduct. However, when the reaction was carried out under high-intensity ultrasound or microwaves, attack by the nucleophile was strongly promoted and water no longer reacted. Best results were achieved under simultaneous ultrasound/microwave irradiation: a series of mono-, di- and trisubstituted oxiranes reacted rapidly with sodium azide or 1-(3-chlorophenyl)piperazine, usually leading to the corresponding more substituted alcohols in acceptable to high yields. This catalyst-free, greener protocol achieves a much faster cleavage of epoxides with a high regioselectivity.

Key words

epoxide opening - ultrasound - microwave - reaction in water - one-pot reaction

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Referenzen

References and Notes

1 Kolb HC. Finn MG. Sharpless KB. Angew. Chem. Int. Ed. 2001, 40: 2004

2 Sekar G. Singh VK. J. Org. Chem. 1999, 64: 287

3a Ollevier T. Lavie-Compin G. Tetrahedron Lett. 2004, 45: 49

3b Chakraborti AK. Kondaskar A. Tetrahedron Lett. 2003, 44: 8315

3c Fringuelli F. Pizzo F. Tortoioli S. Vaccaro L. J. Org. Chem. 2004, 69: 7745

3d Sekar G. Singh VK. J. Org. Chem. 1999, 64: 287

4 Fringuelli F. Piermatti O. Pizzo F. Vaccaio L. J. Org. Chem. 1999, 64: 6094

5a Mojtahedi MM. Saidi MR. Bolourtchian M. J. Chem. Res., Synop. 1999, 128

5b Eshghi H. Rahimizadeh M. Shoryabi A. Synth. Commun. 2005, 35: 791

5c Rodríguez-Escrich S. Popa D. Jimeno C. Vidal-Ferran A. Pericàs MA. Org. Lett. 2005, 7: 3829

6 Cravotto G. Cintas P. Chem. Eur. J. 2007, 13: 1902

7 The use of 1-(3-chlorophenyl)piperazine refers to the work of: Narayan N. Muldoon J. Finn MG. Fikin VV. Kolb HC. Sharpless KB. Angew. Chem. Int. Ed. 2005, 44: 3275

8 Cravotto G. Omiccioli G. Stevanato L. Ultrason. Sonochem. 2005, 12: 213

9 Cravotto G. Boffa L. Bia M. Bonrath W. Curini M. Heropoulos GA. Synlett 2006, 2605

10 Cravotto G, Buffa C, and Omiccioli G. inventors; TO patent application A000766.

11 HSAB theory: Huyskens P. Sobczyk L. Majerz I. J. Mol. Struct. 2002, 615: 61

12 Azizi N. Saidi MR. Org. Lett. 2005, 7: 3649

13a Newhall WF. J. Org. Chem. 1964, 29: 185

13b Steiner D. Ivison L. Goralski CT. Appell RB. Gojkovic JR. Singaram B. Tetrahedron: Asymmetry 2002, 13: 2359

13c Davis CE. Bailey JL. Lockner JW. Coates RM. J. Org. Chem. 2003, 68: 75

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General Procedure
In a 50 mL two-necked round-bottomed flask (equipped with an optical-fiber thermometer for reactions under MW or combined US/MW) the epoxide (2.5 mmol), the amine (or NaN₃, 2.5 mmol), and H₂O (15 mL) were mixed and subjected to procedures 1-4.

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2-[4-(3-Chlorophenyl)piperazin-1-yl]-2-phenylethanol (1Aα): pale yellow oil; R _f = 0.56 (CHCl₃-MeOH, 19:1). IR (film): 3584, 1595, 1452, 1238, 1028, 954, 765 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.37-7.22 (m, 5 H, H-2′, -3′, -4′, -5′, -6′), 7.14 (t, J = 8.1 Hz, 1 H, H-5′′′), 6.83-6.72 (m, 3 H, H-2′′′, -4′′′, -6′′′), 4.03 (m, 1 H, H-2), 3.74 (m, 2 H, H-2, -3), 3.20 (m, 4 H, H-3′′a,b, H-5′′a,b), 2.74-2.54 (m, 4 H, H-2′′a,b, H-6′′a,b). MS (CI, isobutane): m/z = 317 [MH]⁺.

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2-[4-(3-Chlorophenyl)piperazin-1-yl]-1-phenylethanol (1Aβ): pale yellow oil; R _f = 0.43 (CHCl₃-MeOH, 19:1). IR (film): 3400, 1595, 1566, 1481, 1244, 1057, 947, 777 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.46-7.38 (m, 5 H, H-2′, -3′, -4′, -5′, -6′), 7.22 (t, J = 8.1 Hz, 1 H, H-5′′′), 6.94-6.83 (m, 2 H, H-2′′′, -4′′′, -6′′′), 4.86 (m, 1 H, H-1), 3.31 (m, 4 H, H-3′′a,b, H-5′′a,b), 2.95-2.92 (m, 2 H, H-2′′a,b), 2.70-2.56 (m, 4 H, H-2, -3, H-6′′a,b). MS (CI, isobutane): m/z = 317 [MH]⁺.

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2-{3-[4-(3-Chlorophenyl)piperazin-1-yl]-2-hydroxypropyl} isoindoline-1,3-dione (2Aβ): pale yellow oil; R _f = 0.39 (CHCl₃-MeOH, 19:1). IR (film): 3327, 1626, 1576, 1437, 1244, 893 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.87-7.81 (m, 4 H, H-3, -4, -5, -6,), 7.17 (m, 1 H, H-5′′′), 6.80-6.65 (m, 3 H, H-2′′′, -4′′′, -6′′′), 4.21 (m, 1 H, H-2′), 3.50 (m, 2 H, H-1′a,b), 2.57 (m, 2 H, H-3′a,b), 2.90-2.40 (m, 8 H, H-2′′a,b, H-3′′a,b, H-5′′a,b, H-6′′a,b). MS (CI, isobutane): m/z = 400 [MH]⁺.

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1-[4-(3-Chlorophenyl)piperazin-1-yl]octan-2-ol (3Aβ): pale yellow oil; R _f = 0.40 (hexane-EtOAc, 7:3). IR (film): 3460, 1595, 1487, 1234, 1153, 987, 837, 769 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.10 (t, J = 8.1 Hz, 1 H, H-2′′), 6.85-6.50 (m, 3 H, H-4′′, -5′′, -6′′), 3.70 (m, 1 H, H-2), 3.10 (m, 4 H, H-3′a,b, H-5′a,b), 2.75 (m, 2 H, H-2′a,b), 2.50 (m, 2 H, H-6′a,b), 2.30 (m, 2 H, H-1a,b), 1.50-1.00 (m, 10 H, H-3a,b, H-4a,b, H-5a,b, H-6a,b, H-7a,b), 0.95 (br s, 3 H, CH₃). MS (CI, isobutane): m/z = 325 [MH]⁺.

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trans-2-[4-(3-Chlorophenyl)piperazin-1-yl]cyclohexanol (4A): pale yellow oil; R _f = 0.13 (PE-EtOAc, 8:2). IR (film): 3462, 1597, 1495, 1263, 1105, 1014, 954, 771, 681 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.02-6.77 (m, 4 H, H-2′′, -4′′, -5′′, -6′′), 4.16 (m, 1 H, H-1), 3.43 (m, 1 H, H-2), 3.23-3.19 (m, 4 H, H-3′a,b, H-5′a,b), 2.88 (m, 2 H, H-2′a,b), 2.58 (m, 2 H, H-5′a,b), 2.40-1.15 (m, 8 H, H-3,a,b, H-4a,b, H-5a,b, H-6a,b). MS (CI, isobutane): m/z = 295 [MH]⁺.

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(1R,2R)-2-[4-(3-Chlorophenyl)piperazin-1-yl]-1-methyl-4-(prop-1-en-2-yl)cyclohexanol (5Aβ): pale yellow oil; R _f = 0.62 (hexane-EtOAc, 7:3). IR (film): 3462, 2361, 1595, 1450, 1238, 1126, 987, 767 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.17 (t, J = 8.1 Hz, 1 H, H-2′′′), 6.87 (m, 3 H, H-4, -5, -6), 4.96 (m, 1 H, H-9a), 4.87 (m, 1 H, H-9b), 3.47 (m, 1 H, H-2), 3.22 (m, 4 H, H-3′′a,b, H-5′′a,b), 2.90 (m, 2 H, H-2′′a,b), 2.68 (m, 2 H, H6′′a,b), 2.5 (br s, 1 H, OH). MS (CI, isobutane): m/z = 349 [MH]⁺.

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(1R,2R,4R)-2-Azido-1-methyl-4-(prop-1-en-2-yl)cyclo-hexanol (5Bβ): colorless oil; R _f = 0.24 (CHCl₃-MeOH, 19:1). IR (film): 3450, 2094, 1645, 1454, 1261, 1032, 891 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 4.8 (m, 2 H, H-9a,b), 3.55 (br s, 1 H, H-2), 2.20 (m, 1 H, H-4), 2.00 (m, 1 H, H-3a), 1.85 (m, 1 H, H-3b), 1.73 (m, 3 H, H-10, CH₃), 1.45 (br s, 1 H, OH), 1.40 (m, 3 H, H-7, CH₃). MS (CI, isobutane): m/z = 196 [MH]⁺.