Polymer supported bases in combinatorial chemistry: Synthesis of aryl ethers from phenols and alkyl halides and aryl halides

Tetrahedron Letters

Volumn 38, Issue 42, 1997, Pages 7337-7340

  Xu, Wei ^a   Mohan, Raju ^a   Morrissey, Michael M ^a  

^a BAYER AG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ETHER DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IN VITRO STUDY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; REACTION ANALYSIS; TECHNIQUE;

EID: 0030767571     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)01782-6     Document Type: Article

References (17)

1. Gallop, M. A.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gordon, E. M. J. Med. Chem. 1994, 37, 1233. Gordon, E. M.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. J. Med. Chem. 1994, 37, 1385.
2. Gallop, M. A.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gordon, E. M. J. Med. Chem. 1994, 37, 1233. Gordon, E. M.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. J. Med. Chem. 1994, 37, 1385.
3. For literature precedence using solid supported scavenging agents in solution phase reactions see: Kaldor, S. W.; Siegel, M. G.; Fritz, J. E.; Dressman, B. A.; Hahn, P. J. Tetrahedron Lett. 1996, 37, 7193. Booth, R. J.; Hodges, J. C. J. Am. Chem. Soc. 1997, 119, 4882.
4. For literature precedence using solid supported scavenging agents in solution phase reactions see: Kaldor, S. W.; Siegel, M. G.; Fritz, J. E.; Dressman, B. A.; Hahn, P. J. Tetrahedron Lett. 1996, 37, 7193. Booth, R. J.; Hodges, J. C. J. Am. Chem. Soc. 1997, 119, 4882.
5. The polymer supported base PTBD used in this work was purchased from Aldrich/Fluka.
6. Iijima, K.; Fukuda, W.; Tomoi, M. J. Macromol Sci. Pure Appl. Chem. 1992, A29, 249.
7. McKay, A. F.; Kreling, M. E. Can. J. Chem. 1957, 35, 1438-1445. Schmidtchan, F. P. Chem. Ber. 1981, 93, 273.
8. McKay, A. F.; Kreling, M. E. Can. J. Chem. 1957, 35, 1438-1445. Schmidtchan, F. P. Chem. Ber. 1981, 93, 273.
9. Angst, C.; Kratky, C.; Eschenmoser, A. Angew. Chem. Int. Ed. Engl. 1981, 20, 263.
10. Schwesinger, R. Chimia, 1985, 39, 269.
11. Hilpert, K.; Leumann, C.; Davis, A. P.; Eschenmoser, A. J. Chem. Soc. Chem. Commun. 1983, 1401.
12. Schuchardt, U.; Vargas, R. M.; Gelbard, G. J. Mol. Catal. A: Chem. 1996, 109(1), 37.
13. Tamura, Y.; Fukuda, W.; Tomoi, M. Synth. Commun. 1994, 24(20), 2907.
14. A mixture of 6-bromo-2-naphthol (0.060 mmol), PTBD (0.125 mequiv), 2-methylnaphthalene (0.060 mmol, as HPLC internal standard), and MeCN (0.6 mL) was vortexed at 25 °C for 36 h. HPLC detected <1% of 6-bromo-2-naphthol remaining in the supernatant solution. Then 4-cyanobenzyl bromide (0.050 mmol) was added. The mixture was vortexed at 25 °C until the bromide was completely consumed (20 h), and filtered. After removal of MeCN and 2-methylnaphthalene in vacuo, the aryl benzyl ether product (13 mg, 77% yield) was obtained in 92% purity (HPLC). The product is identical to the standard prepared from a direct reaction of the bromonaphthol and the bromide with PTBD in MeCN.
15. For a discussion of a related ionic form in resin beads, see Ref. 4.
16. In some cases where the phenol alkylation reaction is relatively slow, the alkylation of PTBD with alkyl halide may become competitive, thus results in a moderate yield of the phenol alkylation product.
17. 3): 8.22 (d, J=9.3 Hz, 2H), 7.40 (d, J=9.3 Hz, 2H), 7.05 (d, J=6.6 Hz, 2H), 7.02 (d, J=6.6 Hz, 2H) ppm.