Subsupercritical Water Generated by Inductive Heating Inside Flow Reactors Facilitates the Claisen Rearrangement

Abstract

Claisen rearrangement of electron-deficient O-allylated phenols, including fluorine-modified phenols, is facilitated in aqueous media at high temperatures and pressures under flow conditions, as opposed to organic solvents. The O-allylation of phenols can be coupled with the Claisen rearrangement in an integrated flow system.

Key words

Claisen rearrangement - flow chemistry - fluorobenzenes - inductive heating - supercritical water

• References and Notes

• 1 Claisen L. Ber. Dtsch. Chem. Ges. 1912; 45: 3157
• 2a Bennett GB. Synthesis 1977; 589
• 2b Ziegler FE. Acc. Chem. Res. 1977; 10: 227
• 2c Bartlett PA. Tetrahedron 1980; 36: 2
• 2d Ryan JP, O’Connor PR. J. Am. Chem. Soc. 1952; 74: 5866

Reviews:
• 3a Martín Castro AM. Chem. Rev. 2004; 104: 2939
• 3b The Claisen Rearrangement: Methods and Applications. Hiersemann M, Nubbemeyer U. Wiley-VCH; Weinheim: 2007
• 4 Kincaid JF, Tarbell DS. J. Am. Chem. Soc. 1939; 61: 3085
• 5a Hurd CD, Pollack MA. J. Org. Chem. 1939; 3: 550
• 5b Goering HL, Jacobson RR. J. Am. Chem. Soc. 1958; 80: 3277
• 5c White WN, Gwynn D, Schlitt R, Girard C, Fife W. J. Am Chem. Soc. 1958; 80: 3271
• 6 Li C.-J, Chen L. Chem. Soc. Rev. 2006; 35: 68
• 7 Savage PE. Chem. Rev. 1999; 99: 603
• 8a Narayan S, Muldoon J, Finn MG, Fokin VV, Kolb HC, Sharpless KB. Angew. Chem. Int. Ed. 2005; 44: 3275
• 8b Vogel H, Krammer P. J. Supercrit. Fluids 2000; 16: 189
• 9 Kirschning A, Kupracz L, Hartwig J. Chem. Lett. 2012; 41: 562
• 10 Kirschning A, Solodenko W, Mennecke K. Chem. Eur. J. 2006; 12: 5972
• 11 Wang W, Tuci G, Duong-Viet C, Liu Y, Rossin A, Luconi L, Nhut J.-M, Nguyen-Dinh L, Pham-Huu C, Giambastiani G. ACS Catal. 2019; 9: 7921
• 12a Ceylan S, Friese C, Lammel C, Mazac K, Kirschning A. Angew. Chem. Int. Ed. 2008; 47: 8950; Angew. Chem.; 2008, 120, 9083
• 12b Ceylan S, Coutable L, Wegner J, Kirschning A. Chem. Eur. J. 2011; 17: 1884
• 13 Hartwig J, Kirschning A. Chem. Eur. J. 2016; 22: 3044
• 14a Chemical Synthesis Using Supercritical Fluids . Jessop PG, Leitner W. Wiley-VCH; Weinheim: 1999
• 14b Kruse A, Dinjus E. J. Supercrit. Fluids 2007; 39: 362
• 14c Marre S, Roig Y, Aymonier C. J. Supercrit. Fluids 2012; 66: 251
• 15a Noel T, Hessel V, Shahbazali E, Spapens M, Kobayashi H, Ookawara S. Chem. Eng. J. 2015; 281: 144
• 15b Noel T, Hessel V, Kobayashi H, Driessen B, van Osch DJ. G. P, Talla A, Ookawara S. Tetrahedron 2013; 69: 2885
• 16 Hammes-Schiffer S, Hu H, Kobrak MN, Xu C. J. Phys. Chem. A 2000; 104: 8058
• 17 White WN, Wolfarth EF. J. Org. Chem. 1970; 35: 3585
• 18 Two-Step Flow Synthesis of 2-Allyl-4,6-difluorophenol (23) An allyl bromide solution in benzene (1 M) was combined with a 0.1 M aqueous sodium phenolate solution (7, sodium salt) via a static mixer. An additional 0.5 mol/L of sodium hydroxide was added to the aqueous sodium phenolate solution. Both reagents were pumped at a flow rate of 0.3 mL/min through a 1/8′′ steel reactor (coiled, V = 3.4 mL). The reactor was heated to 110 °C in an oscillating electromagnetic high-frequency field. The reaction mixture was then passed through a second reactor (3.2 mL), which was heated to a temperature of 265 °C at a pressure of 183–184 bar. The reaction mixture was collected over a period of 25 min and extracted with diethyl ether (3 × 10 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated under reduced pressure and co-evaporated with methanol. The residue obtained was purified by flash chromatography (pentane to pentane/diethyl ether 10%). 2-Allyl-4,6-difluorophenol (24) Yellow oil (80.2 mg, 0.47 mmol; 64%). ¹H NMR (600 MHz, CDCl₃, CHCl₃ = 7.26 ppm): δ = 6.75–6.71 (1 H, m, H-7), 6.68–6.66 (1 H, m, H-5), 5.98–5.92 (1 H, m, H-2), 5.14–5.10 (2 H, m, H-1), 4.99 (1 H, br s, OH), 3.41–3.40 (2H, m, H-3). ¹³C NMR (150 MHz, CDCl₃, CDCl₃ = 77.16 ppm): δ = 156.5–154.8 (q, dd, J = 240.6 Hz, 11.5 Hz, C-6), 151.4–149.7 (q, dd, J = 238.7 Hz, 12.7 Hz, C-8), 138.0–137.9 (q, dd, J = 14.0 Hz, 3.5 Hz, C-9), 135.3 (t, C-2), 129.6–129.5 (q, dd, J = 8.3 Hz, 2.6 Hz, C-4), 116.9 (s, C-1), 112.0–111.8 (t, dd, J = 22.6 Hz, 3.4 Hz, C-5), 102.0–101.7 (t, dd, J = 27.2 Hz, 23.0 Hz, C-7), 34.0–33.9 (s, dd, J = 3.1 Hz, 1.4 Hz C-3). HRMS (EI): m/z calcd for C₉H₈OF₂: 170.0543; found: 170.0543; R_f = 0.24 (pentane/Et₂O = 9:1).