Solid-Supported Sulfonylhydroxylamine as an Effective N-Aminating Agent of Anilines

Hiroshi Ohno; Hiroshi Tanaka; Takashi Takahashi

doi:10.1055/s-2005-865218

LETTER

Solid-Supported Sulfonylhydroxylamine as an Effective N-Aminating Agent of Anilines

Hiroshi Ohno*^a, Hiroshi Tanaka^b, Takashi Takahashi*^b
^a Department of Medicinal Chemistry, Pharmaceutical Research Laboratory, Toray Industries, Inc., 1111 Tebiro, Kamakura, Kanagawa 248-8555, Japan
Fax: +81(467)324791; e-Mail: Hiroshi_Ono@nts.toray.co.jp;
^b Department of Applied Chemistry, Tokyo Institute of Technology, Meguro, Tokyo 152-8552, Japan

Abstract

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Abstract

An effective method for the synthesis of aryl hydrazines by amination of anilines using the solid-supported phenylsulfonylhydroxylamine was described. Treatment of aniline with the solid-supported aminating agent, followed by removal of the resin, provided the corresponding hydrazine in 21% yield. The resulting hydrazines were directly adapted to the solid-phase synthesis of indoles, providing nine naltrindole derivatives varying the substituents on the aromatic rings.

Key words

electrophilic aminations - hydrazines - indoles - naltrindoles - solid-phase synthesis

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Referenzen

References

For reviews on synthesis of heterocycles, see:

1a Krchnak V. Holladay MW. Chem. Rev. 2002, 102: 61

1b Franzen RG. J. Comb. Chem. 2000, 2: 195

1c Horton DA. Bourne GT. Smythe ML. Chem. Rev. 2003, 103: 893

For recent studies on synthesis of aryl hydrazines and their derivatives, see:

2a Wang Z. Skerlj RT. Bridger GJ. Tetrahedron Lett. 1999, 40: 3543

2b Wagaw S. Yang HB. Buchwald SL. J. Am. Chem. Soc. 1998, 120: 6621

2c Hartwig JF. Angew. Chem. Int. Ed. 1998, 37: 2090

2d Demers JP. Klaubert DH. Tetrahedron Lett. 1987, 28: 4933

3 On the biological activity of indoles, see: Sunberg RJ. Indoles Academic Press; London: 1996. and references therein

4 Haddad N. Baron J. Tetrahedron Lett. 2002, 43: 2171 ; and references therein

5 Hunsberger IM. Shaw ER. Fugger J. Ketcham R. Lednicer D. J. Org. Chem. 1956, 21: 394

6 Brown DW. Mahon MF. Ninan A. Sainsbury M. Shertzer HG. Tetrahedron 1993, 49: 8919

7 For a review on sulfonylhydroxylamine, see: Tamura Y. Minamikawa J. Ikeda M. Synthesis 1977, 1

For synthesis of sulfonylhydroxylamine, see:

8a Glover EE. Rowbottom KT. J. Chem. Soc., Perkin Trans. 1 1976, 367

8b Batori S. Timari G. Koczka I. Hermecz I. Bioorg. Med. Chem. Lett. 1996, 6: 1507

8c Greck C. Bischoff L. Girard A. Hajicek J. Genet JP. Bull. Soc. Chim. Fr. 1994, 131: 429

9 Explosion in attempting to dry O-mesitylenesulfonyl-hydroxylamine has been reported, see: Scopes DIC. Kluge AF. Edwards JA. J. Org. Chem. 1977, 42: 376

For solid-supported reagent, see:

10a Booth RJ. Hodges JC. Acc. Chem. Res. 1999, 32: 18

10b Parlow JJ. Devraj RV. South MS. Curr. Opin. Chem. Biol. 1999, 3: 320

10c Thompson LA. Curr. Opin. Chem. Biol. 2000, 4: 324

10d Ley SV. Baxendale IR. Bream RN. Jackson PS. Leach AG. Longbottom DA. Nesi M. Scott JS. Storer RI. Taylor SJ. J. Chem. Soc., Perkin Trans. 1 2000, 3815

10e Guillier F. Orain D. Bradley M. Chem. Rev. 2000, 100: 2091

11a Portoghese PS. Sultana M. Nagase H. Takemori AE. J. Med. Chem. 1988, 31: 281

11b Portoghese PS. Sultana M. Takemori AE. J. Med. Chem. 1990, 33: 1714

12

Procedure for the Preparation of 7.
To a mixture of PS-TsCl (Argonout, 1.97 mmol/g, 2.0 g, 3.9 mmol) and N-Boc-hydroxylamine (1.05 g, 7.9 mmol) in THF (32 mL) was added THF solution (4 mL) of Et₃N (1.1 mL, 7.9 mmol) slowly at 0 °C. The mixture was shaken for 1.5 h at r.t. After filtration of the mixture, the resulting resin was washed with THF, H₂O, and THF, and dried in vacuo to give resin-supported N-Boc sulfonyl hydroxylamine 7 (2.6 g). IR (resin): 1475, 1396, 1173 cm^-1. Anal. Found: C, 68.78; H, 7.40; N, 2.22; Cl, 0.02; S, 5.52%.

13

The ratio was estimated by ¹H NMR measurement of the crude mixture.

14

Typical Experimental Procedure.
To resin-supported N-Boc sulfonyl hydroxylamine (7, 100 mg), TFA (1 mL, pre-cooled at 0 °C) was added at r.t., and the mixture was shaken for 1 min at r.t. After filtration of the mixture, the resulting resin was washed with H₂O, THF, and CH₂Cl₂ (pre-cooled at 0 °C) to give the polystyrene-supported sulfonyl hydroxylamine 1B. The resulting resin was used for next amination without drying. To the resulting resin 1B was added aniline (27 µL, 0.29 mmol) in CH₂Cl₂ (0.5 mL, pre-cooled at 0 °C), and the mixture was shaken for 10 min at r.t. After filtration of the mixture followed by washing with CH₂Cl₂, the resulting resin were treated with CH₂Cl₂-HCl (10 M) in MeOH (1:1), filtered, and then washed with CH₂Cl₂-HCl (10 M) in MeOH (1:1). The combined filtrates were evaporated, and dried in vacuo to give of crude phenylhydrazine HCl (17.1 mg). Further purification was achieved by silica gel column chromatography followed by adding 10 M HCl in MeOH to give phenylhydrazine HCl (4.0 mg, 28 µmol).

15 Robinson R. The Fischer Indole Synthesis Wiley-Interscience; New York: 1982.

16a Tanaka H. Ohno H. Kawamura K. Ohtake A. Nagase H. Takahashi T. Org. Lett. 2003, 5: 1159

16b Ohno H. Tanaka H. Takahashi T. Synlett 2004, 508

17

The lower yield than previously reported [16a] was due to the different ways of estimation of the yield. The yield was determined by measurement of mass weight of cleavage product in the former paper, on the other hand in this paper the yield is isolated yield.

18

Spectra of 8d: ¹H NMR (400 MHz, CD₃OD): δ = 0.13-0.23 (2 H, m), 0.52-0.61 (2 H, m), 0.93 (1 H, m), 1.30 (3 H, t, J = 7.6 Hz), 1.72 (1 H, d, J = 12.2 Hz), 2.28-2.50 (4 H, m), 2.56 (1 H, d, J = 15.9 Hz), 2.73 (1 H, d, J = 15.9 Hz), 2.73-2.90 (4 H, m), 3.17 (1 H, d, J = 18.6 Hz), 3.40 (1 H, d, J = 6.3 Hz), 5.59 (1 H, s), 6.53 (1 H, d, J = 8.1 Hz), 6.56 (1 H, d, J = 8.1 Hz), 7.00 (1 H, d, J = 1.7 Hz), 7.34 (1 H, d, J = 1.7 Hz). ¹³C NMR (150.8 MHz, CD₃OD): δ = 4.2, 4.8, 10.3, 14.6, 24.1, 25.1, 29.8, 32.8, 45.0, 60.4, 63.4, 74.4, 85.7, 111.1, 113.0, 118.2, 119.6, 119.7, 124.4, 126.0, 129.3, 130.2, 131.8, 131.9, 135.8, 140.8, 144.5. MS (ESI): 521 [M + H]⁺.
Spectra of 8e: ¹H NMR (400 MHz, CD₃OD): δ = 0.13-0.22 (2 H, m), 0.51-0.60 (2 H, m), 0.93 (1 H, m), 1.73 (1 H, d, J = 12.5 Hz), 2.28-2.47 (4 H, m), 2.49 (3 H, s), 2.57 (1 H, d, J = 15.9 Hz), 2.68-2.85 (2 H, m), 2.76 (1 H, d, J = 15.9 Hz), 3.17 (1 H, d, J = 18.6 Hz), 3.40 (1 H, d, J = 6.3 Hz), 5.59 (1 H, s), 6.52 (1 H, d, J = 8.1 Hz), 6.55 (1 H, d, J = 8.1 Hz), 6.90 (1 H, d, J = 8.4 Hz), 7.16 (1 H, d, J = 8.4 Hz). ¹³C NMR (150.8 MHz, CD₃OD): δ = 4.2, 4.8, 10.3, 14.1, 24.1, 29.8, 32.7, 45.0, 60.4, 63.5, 74.4, 85.8, 111.8, 117.8, 118.2, 119.3, 119.6, 120.9, 125.9, 126.2, 128.4, 131.5, 131.9, 138.5, 140.8, 144.5. MS (ESI): 463 [M + H]⁺.
Spectra of 8f: ¹H NMR (400 MHz, CD₃OD): δ = 0.15-0.24 (2 H, m), 0.52-0.62 (2 H, m), 0.95 (1 H, m), 1.26-1.42 (18 H, m), 1.74 (1 H, m), 2.35-2.49 (4 H, m), 2.71-2.81 (3 H, m), 3.18-3.26 (2 H, m), 3.36 (1 H, d, J = 6.3 Hz), 5.61 (1 H, s), 6.53 (1 H, d, J = 8.2 Hz), 6.56 (1 H, d, J = 8.2 Hz), 7.05 (1 H, d, J = 1.7 Hz), 7.20 (1 H, d, J = 1.7 Hz). ¹³C NMR (150.8 MHz, CD₃OD): δ = 4.3, 4.7, 10.3, 24.2, 31.9, 32.2, 33.0, 35.6, 36.3, 36.5, 44.9, 48.0, 60.5, 63.9, 75.0, 86.6, 107.0, 108.9, 115.2, 118.2, 119.5, 122.6, 125.9, 130.9, 132.1, 140.1, 140.8, 144.3, 144.8, 145.1. MS (ESI): 527 [M + H]⁺.
Spectra of 8g: ¹H NMR (400 MHz, CD₃OD): δ = 0.15-0.24 (2 H, m), 0.52-0.61 (2 H, m), 0.94 (1 H, m), 1.73 (1 H, m), 1.81-1.91 (4 H, m), 2.31-2.49 (4 H, m), 2.59 (1 H, d, J = 15.9 Hz), 2.75-2.87 (7 H, m), 3.17 (1 H, d, J = 18.6 Hz), 3.41 (1 H, d, J = 5.9 Hz), 5.60 (1 H, s), 6.52 (1 H, d, J = 8.2 Hz), 6.54 (1 H, d, J = 8.2 Hz), 6.67 (1 H, d, J = 8.1 Hz), 7.10 (1 H, d, J = 8.1 Hz). ¹³C NMR (150.8 MHz, CD₃OD): δ = 4.2, 4.8, 10.2, 24.2, 24.2, 24.9, 25.4, 30.0, 30.6, 32.7, 45.0, 49.9, 60.4, 63.5, 74.4, 86.3, 116.7, 118.1, 119.4, 120.4, 121.5, 125.3, 125.9, 129.5, 131.3, 132.1, 137.7, 140.8, 144.5, 150.4. MS (ESI): 469 [M + H]⁺.
Spectra of 8h: ¹H NMR (400 MHz, CD₃OD): δ = 0.12-0.22 (2 H, m), 0.49-0.60 (2 H, m), 0.92 (1 H, m), 1.75 (1 H, d, J = 12.7 Hz), 2.27-2.46 (4 H, m), 2.66 (1 H, d, J = 15.6 Hz), 2.71-2.76 (1 H, m), 2.83 (1 H, d, J = 18.6 Hz), 2.84 (1 H, d, J = 15.9 Hz), 3.17 (1 H, d, J = 18.6 Hz), 3.42 (1 H, d, J = 6.3 Hz), 5.68 (1 H, s), 6.54 (1 H, d, J = 8.2 Hz), 6.57 (1 H, d, J = 8.2 Hz), 7.45-7.49 (1 H, m), 7.51-7.55 (1 H, m), 7.58 (1 H, s), 8.19-8.23 (2 H, m). ¹³C NMR (150.8 MHz, CD₃OD): δ = 4.2, 4.7, 10.2, 24.1, 29.7, 32.7, 44.8, 60.3, 63.3, 74.4, 85.7, 112.6, 118.0, 119.5, 119.7, 121.7, 122.8, 123.5, 123.9, 125.3, 125.8, 125.9, 126.8, 128.2, 129.9, 131.7, 132.3, 140.6, 144.4. MS (ESI): 499 [M + H]⁺.
Spectra of 8i: ¹H NMR (400 MHz, CD₃OD): δ = 0.12-0.24 (2 H, m), 0.51-0.62 (2 H, m), 0.87-0.97 (1 H, m), 1.73-1.76 (1 H, m), 2.28-2.50 (4 H, m), 2.63 (1 H, d, J = 14.6 Hz), 2.72-2.88 (2 H, m), 2.81 (1 H, d, J = 15.6 Hz), 3.18 (1 H, d, J = 18.6 Hz), 3.42 (1 H, d, J = 6.6 Hz), 3.81 (1 H, d, J = 22.0 Hz), 3.90 (1 H, d, J = 21.7 Hz), 5.63 (1 H, s), 6.54 (1 H, d, J = 8.1 Hz), 6.56 (1 H, d, J = 8.1 Hz), 7.15-7.19 (1 H, m), 7.26-7.30 (1 H, m), 7.31 (1 H, d, J = 8.1 Hz), 7.41 (1 H, d, J = 8.3 Hz), 7.46 (1 H, d, J = 7.3 Hz), 7.68 (1 H, d, J = 7.6 Hz). ¹³C NMR (150.8 MHz, CD₃OD): δ = 4.2, 4.8, 10.3, 24.2, 30.1, 32.7, 35.2, 45.0, 60.4, 63.5, 74.4, 86.1, 112.2, 112.4, 118.2, 118.5, 119.6, 119.8, 125.6, 126.0, 126.1, 126.5, 127.4, 127.6, 131.0, 132.1, 135.5, 137.8, 140.9, 143.5, 144.4, 144.6. MS (ESI): 503 [M + H]⁺.