Synthesis of Aryl Azides via Post-Cleavage Modification of Polymer-Bound Triazenes

Abstract

Starting from immobilized arenes on the triazene T1 linker resin, cleavage was achieved by trifluoroacetic acid in the presence of trimethylsilyl azide to obtain aryl azides in good yields and excellent purities. A novel cleavage protocol has been introduced and analytical and preparative applications have been ­presented.

Key words

aryl azides - post-cleavage modification - polymer-bound triazenes

References

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22

Bräse, S.; Lormann, M.; Vogt, H. Scope and Limitation of a Tin Promoted Amidation on Solid Phase: A New Monitoring for the T1 Triazene Linker; Proceedings of ECSOC-4, The Third International Electronic Conference on Synthetic Organic Chemistry, September 1-30, 2000, see also http://www.mdpi.org/ecsoc-4.htm.

31

Gil, C.; Bräse, S. unpublished results.

32

Representative Procedure for Synthesis of a T1-Resin: The aniline 2n (3.68 g, 20.2 mmol) was dissolved in 100 mL of CH₂Cl₂ and BF₃·OEt₂ (4.26 g, 30.0 mmol) was added at r.t. The mixture was cooled to -15 °C and isoamyl nitrite (3.83 g, 32.7 mmol) was added dropwise with stirring for 15 min. After stirring for 4 h the mixture was cooled to -70 °C and the solid diazonium salt was filtered off, washed with precooled Et₂O and suspended in MeCN at -40 °C. In a second flask, the benzylamine resin 1 (5.00 g, 4.65 mmol, loading 0.93 mmol/g) was dissolved in THF at -20 °C and pyridine (5.87 g, 74.0 mmol) was added. The cooled suspension of the diazonium salt was added to the benzylamine resin suspension and the reaction mixture was stirred slowly for 6 h. It was allowed to warm up to r.t. The resin was filtered off, washed sequentially with THF, CH₂Cl₂, MeOH, pentane, DMF and dried under high vacuum.

33

Representative Procedure for Cleavage of a T1-Resin: The resin 3n (0.40 g, loading 0.74 mmol/g) was suspended in 5 mL of CH₂Cl₂ and trifluoroacetic acid (0.30 mL, 4.0 mmol) was added dropwise at r.t. After 2-5 min, trimethylsilyl azide (0.15 mL, 1.2 mmol) was added to the resin and after few minutes (5-10) the mixture was filtered and the solvent was removed by evaporation. 1-Azido-5-methoxy-2-methyl-4-nitro-benzene (4n): 58.5 mg, 79% yield. GC: R_t = 13.99 min. IR (KBr disk): 2100 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.18 (s, 3 H), 3.99 (s, 3 H), 6.73 (s, 1 H) 7.79 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 16.2 (C_p), 56.8 (C_p), 102.9 (C_p), 121.8 (C_q), 128.6 (C_p), 135.5 (C_q), 144.6 (C_q), 152.9 (C_q). MS-DIP: m/z (%) = 208 (51), 180 (92), 152 (50), 122 (27), 106 (10), 95 (100), 92 (73), 80 (95), 77 (12), 63 (23).

36

Krasinski, A., Fokin, V. V., Sharpless, K. B.; Org. Lett., submitted.

38

The crude solution of the azide (4t) was washed with H₂O to remove the excess of trimethyl silyl azide, and norbornene was added. After 3 d at 25 °C the solvent was evaporated and the residue was recrystallized from petroleum ether/EtOAc (1:1).
3-(2′-Bromophenyl)-3,4,5-triazatri-cyclo[5.2.1.0^2,6]dec-4-ene (5): >95%. IR (KBr): 3403 (w), 3068 (w), 2968 (s), 2874 (m), 2662 (w), 1921 (w), 1802 (w), 1586 (m), 1503 (m), 1469 (s), 1325 (m), 1310 (m), 1300 (m), 1260 (m), 1247 (m), 1216 (w), 1159 (w), 1124 (m), 1079 (m), 1046 (s), 1028 (m), 1012 (m), 974 (s), 952 (m), 918 (s), 888 (w), 863 (w), 846 (m), 805 (w), 754 (s), 714 (w), 700 (m), 640 (m) cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.08-1.10 (complex, 2 H, 10-H), 1.20 (m, 1 H, 9-H), 1.34 (m, 1 H, 8-H), 1.44 (m, 1 H, 9-H), 1.55 (m, 1 H, 8-H), 2.06 (d, ³ J = 4.3 Hz, 1 H, 1-H), 2.70 (d, ³ J = 4.4 Hz, 1 H, 7-H), 4.25 (d, ³ J = 9.1 Hz, 1 H, 2-H), 4.61 (d, ³ J = 9.2 Hz, 1 H, 6-H), 7.07 (ddd, ³ J = 8.0 Hz, ³ J = 7.3 Hz, ⁴ J = 1.7 Hz, 1 H, 5′-H), 7.28 (ddd, ³ J = 8.0 Hz, ³ J = 7.3 Hz, ⁴ J = 1.4 Hz, 1 H, 4′-H), 7.34 (dd, ³ J = 8.0 Hz, ⁴ J = 1.7 Hz, 1 H, 3′-H), 7.59 (dd, ³ J = 8.0 Hz, ⁴ J = 1.4 Hz, 1 H, 6′-H). ¹³C NMR (75 MHz, CDCl₃): δ = 24.9 (-, 9-CH₂), 25.4 (-, 8-CH₂), 31.8 (-, 10-CH₂), 40.1 (+, 1-CH), 40.7 (+, 7-CH), 61.4 (+, 2-CH), 87.0 (+, 6-CH), 116.1 (q, C-2′), 125.7 (+, C-3′), 127.1 (+, C-5′), 128.0 (+, C-4′), 133.9 (+, C-6′), 139.9 (q, C-1′). MS (FAB): m/z (%) = 292/294 (100/98) [MH⁺], 263/265 (26/25) [C₁₃H₁₄NBr⁺], 234/236 (9/11). MS (EI): m/z (%) = 263/265 (C₁₃H₁₄NBr⁺, 20/20) [M⁺ - N₂], 235/236 (96/100), 222/224 (5/5), 208/210 (9/8), 197/199 (22/18), 182/184 (24/33), 171/173 (30/29), 155/157 (27/26), 143 (7), 130 (15), 118 (11), 93 (90), 91 (32), 77 (32). HRMS (EI): calcd 291.0371 for M⁺ resp. 263.0310 for (M⁺ - N₂), found 263.0308. Product undergoes thermal decomposition while GC and EI measurements are taken.