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Synlett 2010(5): 812-816  
DOI: 10.1055/s-0029-1219360
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A New, Practical and Efficient Method for Protecting Alcohols as tert-Butyl Ethers

Alessandro Bargea, Ernesto G. Occhiato*b, Cristina Prandi*c, Dina Scarpib, Silvia Tabassoc, Paolo Venturelloc
a Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via P. Giura 9, 10125 Torino
b Dipartimento di Chimica, Università di Firenze, Via della Lastruccia 13, 50019 Sesto Fiorentino, Italy
e-Mail: ernesto.occhiato@unifi.it;
c Dipartimento di Chimica Generale e Chimica Organica, Università di Torino, Via P. Giuria 7, 10125 Torino, Italy
e-Mail: cristina.prandi@unito.it;
Further Information

Publication History

Received 1 December 2009
Publication Date:
08 February 2010 (online)

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Abstract

A new method for protecting alcohols as tert-butyl ethers is reported. The reaction is performed in tert-butyl acetate in the presence of a catalytic amount of HClO4. The process is extremely efficient and primary and secondary alcohols as well as diols are protected under very mild conditions. Remarkably, tert-butyl acetate can be easily recovered after the workup of the reaction and recycled.

Key words

protecting groups - tert-butyl ethers - alcohols - tert-­butyl acetate

    References and Notes

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6

The conversion of unprotected 5-aminopentan-1-ol into the corresponding 5-tert-butoxypentan-1-amine has been successfully performed in the presence of 0.5 equiv of HClO4.

9

Several phenols have also been considered. Unfortunately most of them mainly gave FC alkylation products. Only mono- and di-nitro phenols were converted into the correspondent tert-butyl ethers although in low yields.

10

General Procedure for the Synthesis of tert-Butyl Ethers: To a solution of the alcohol in t-BuOAc, was added HClO4 and the mixture was stirred at 25 ˚C until the reaction was complete (reaction monitored by TLC or GC). Na2CO3 (2 equiv) was added and the mixture was stirred for 40 min. After filtration, the solvent was removed under vacuum (for the re-use of t-BuOAc, this was washed with a saturated solution of NaHCO3, then with H2O and finally dried over Na2SO4). The tert-butyl ether was separated from the residual alcohol by flash chromatography on silica gel (petroleum ether-Et2O or n-hexane-EtOAc). Compounds 4, [7] 5, [³d] 6, [4c] 7, [¹4] 8, [³d] 10, [³d] 12a, [¹²] [¹³] 12b, [¹¹] [¹³] 13a, [8] and 13b [8] are known, and their spectroscopic data correspond to those reported. 1: ¹H NMR (CDCl3, 200 MHz): δ = 7.40-7.31 (m, 5 H), 7.30-7.15 (m, 5 H), 5.26-5.12 (br s, 1 H), 5.09 (s, 2 H), 4.03-3.86 (s, 1 H), 3.34-3.20 (m, 2 H), 2.94-2.83 (m, 2 H), 1.16 (s, 9 H); ¹³C NMR (CDCl3, 50.33 MHz): δ = 155.8 (s), 138.3 (s), 136.5 (s), 129.4 (d, 2 C), 128.4 (d, 2 C), 128.2 (d, 2 C and 1 C), 128.0 (d, 2 C), 126.2 (d), 72.8 (s), 66.5 (t), 61.1 (t), 52.5 (d), 37.8 (t), 27.5 (q, 3 C). MS (ESI): m/z (%) = 364 (100)[M+ + Na], 341 (14) [M]+, 286 (19). 2: ¹H NMR (CDCl3, 200 MHz): δ = 7.76 (d, J = 7.3 Hz, 2 H), 7.60 (d, J = 7.3 Hz, 2 H), 7.43-7.29 (m, 4 H), 5.68-5.52 (br s, 1 H), 4.41-4.36 (m, 2 H), 4.28-4.18 (m, 1 H), 3.46 (t, J = 5.5 Hz, 2 H), 3.40-3.20 (m, 2 H), 1.82-1.66 (m, 2 H), 1.21 (s, 9 H); ¹³C NMR (CDCl3, 50.33 MHz): δ = 156 (s), 143.8 (s, 2 C), 141.1 (s, 2 C), 127.4 (d, 2 C), 126.8 (d, 2 C), 124.9 (d, 2 C), 119.7 (d, 2 C), 73.0 (s), 66.4 (t), 60.6 (t), 47.3 (d), 40.1 (t), 29.8 (t), 27.5 (q, 3 C). MS (ESI): m/z (%) = 376 (100)[M+ + Na], 353 (19) [M]+, 298 (6). MS (EI, 70 eV): m/z (%) = 353 (0.1) [M]+, 178 (100). 3: ¹H NMR (CDCl3, 200 MHz): δ = 7.27-7.14 (m, 4 H), 3.52 (t, J = 7.3 Hz, 2 H), 2.79 (t, J = 7.3 Hz, 2 H), 1.16 (s, 9 H); ¹³C NMR (CDCl3, 50.33 MHz): δ = 137.9 (s), 131.7 (s), 130.2 (d, 2 C), 128.1 (d, 2 C), 72.9 (s), 62.7 (t), 36.8 (t), 27.6 (s, 3 C). MS (EI, 70 eV): m/z (%) = 212 (2)[M]+, 182 (3), 57 (100). 9: ¹H NMR (CDCl3, 200 MHz): δ = 3.58-3.65 (m, 1 H), 1.61-1.50 (m, 2 H), 1.34 (br, 20 H), 1.19 (s, 9 H); ¹³C NMR (CDCl3, 50.33 MHz): δ = 73.1 (s), 68.6 (d), 31.9 (t, 2 C), 28.7 (q, 3 C), 24.6 (t, 2 C), 24.0 (t), 23.2 (t, 4 C), 21.1 (t, 2 C). MS (EI, 70 eV): m/z (%) = 240 (3)[M]+, 183 (18), 166 (3), 57 (100). 11: ¹H NMR (CDCl3, 400 MHz): δ = 5.31-5.29 (m, 1 H), 5.10-5.06 (m, 1 H), 3.34-3.26 (m, 1 H), 2.32-2.23 (m, 2 H), 2.12 (ddd, J = 13.4, 4.9, 2.1 Hz, 1 H), 2.06-1.93 (m, 2 H), 1.87-1.79 (m, 4 H), 1.70-1.35 (m, 11 H), 1.68 (s, 3 H), 1.60 (s, 3 H), 1.34-1.00 (m, 7 H), 1.18 (s, 9 H), 0.99 (s, 3 H), 0.93 (d, J = 6.6 Hz, 3 H), 0.670 (s, 3 H); ¹³C NMR (CDCl3, 100.4 MHz): δ = 142, 131, 125, 120, 73.3, 71.4, 56.8, 56.1, 50.3, 42.3, 42.1, 39.8, 37.8, 36.6, 36.1, 35.6, 32.0, 31.9, 31.3, 28.5 (3 C), 28.2, 25.7, 24.7, 24.3, 21.0, 19.3, 18.6, 17.6, 11.8. MS (EI, 70 eV): m/z (%) = 440 (2) [M]+, 57 (100). 17: ¹H NMR (CDCl3, 400 MHz): δ = 5.90 (d, J = 4.4 Hz, 1 H), 5.28 (pseudo q, J = 4.3 Hz, 1 H), 4.09 (dt, J = 13.3, 4.4 Hz, 1 H), 3.79 (s, 3 H), 3.73 (s, 3 H), 3.28 (ddd, J = 13.3, 9.2, 5.5 Hz, 1 H), 2.04 (s, 3 H), 1.98-1.95 (m, 2 H); ¹³C NMR (CDCl3, 100.4 MHz): δ = 170.0 (s), 164.7 (s), 153.9 (s), 135.3 (s), 116.3 (d), 63.5 (d), 53.4 (q), 52.4 (q), 40.5 (t), 29.2 (t), 21.0 (q); MS: m/z (%) = 257 (14)[M]+, 225 (40), 198 (49), 183 (60), 152 (77), 94 (100). 18: ¹H NMR (CDCl3, 200 MHz): δ = 4.00 (s, 2 H), 2.11 (t, J = 4.3 Hz, 2 H), 1.45 (m, 2 H), 1.17 (s, 9 H), 0.86 (t, J = 7.3 Hz, 3 H); ¹³C NMR (CDCl3, 50.33 MHz): δ = 85.1 (s), 81.2 (s), 73.8 (s), 50.6 (t), 27.3 (q), 21.8 (t), 20.7 (t), 13.3 (q). MS (EI, 70 eV): m/z (%) = 139 (88), 81 (100), 79 (96), 59 (74), 57 (63). 19: ¹H NMR (CDCl3, 200 MHz): δ = 4.19 (q, J = 6.6 Hz, 1 H), 2.10 (q, J = 7.5 Hz, 2 H), 1.31 (d, J = 6.6 Hz, 3 H), 1.17 (s, 9 H), 1.10 (t, J = 7.5 Hz, 3 H); ¹³C NMR (CDCl3, 50.33 MHz): δ = 84.8 (s), 82.3 (s), 73.9 (s), 57.0 (d), 27.9 (q), 23.8 (q), 13.6 (q), 12.3 (t). MS (EI, 70 eV): 139 (70), 81 (100), 79 (80), 59 (88), 57 (94).