2-(perfluoroalkyl)ethanols by thermal alkylation of ambidentate lactams with 2-(perfluoroalkyl)-1-iodoalkanes, in the presence of added water. A change in mechanism and stoichiometry of the reaction. Isolation of a water adduct of the lactim ether intermediate

Journal of Organic Chemistry

Volumn 61, Issue 19, 1996, Pages 6504-6516

  Brace, Neal O ^a  

^a WHEATON COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LACTAM DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; MASS SPECTROMETRY; REACTION ANALYSIS;

EID: 0029821222     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo960831g     Document Type: Article

References (33)

1. (a) Brace, N. O. J. Org. Chem. 1995, 60, 2059-2071.
2. (b) Brace, N. O. Reaction of Ambidentate Lactams with 2-(Perfluoroalkyl)-1-iodoethanes. Paper (No. 75) read at Ninth Winter Fluorine Conference, American Chemical Society, St. Petersburg, FL, Feb. 3, 1989. Poster No. 43, Fluorine Division of the 203rd National American Chemical Society Meeting, San Francisco, April 6, 1992.
3. (c) Reference 29 of Brace, N. O. J. Org. Chem. 1995, 60, 2059-2071.
4. Brace, N. O. J. Fluorine Chem. 1986, 31, 151-174.
5. (a) Brace, N. O. J. Org. Chem. 1993, 58, 1804.
6. (b) See Correction in J. Org. Chem. 1994, 59, 3242.
7. DesLongchamps, P. Stereoelectronic Effects in Organic Chemistry; Pergamon Press: New York, 1983; Chapter 4.
8. 3. Scheme 1 shows iminolactam 5 (30-80% yield), the lactim ether salt 6·HI, and 2-(perfluorohexyl)ethene (4) as coproducts of 3. In this system, nucleophilic attack of lactam 2 on lactim ether salt 6·HI produces alcohol 3 and the iminolactam 5. Side product 4 is probably derived from lactim 6 by intramolecular elimination. Selectivity (mol ratio of 3:4) to the desired 2-(perfluorohexyl)ethanol (3) over side-product 4 fell precipitously in the ring size series: (n = 5:6:7) = 18.4:0.73:0.13.
9. -1.
10. alc, without water was unchanged.
11. See supporting information.
12. Glushkov, R. G.; Granik, V. G. In The Chemistry of Lactim Ethers; Katritsky, A. R., Boulton, A. J., Eds.; Advances in Heterocyclic Chemistry, Academic Press: New York, 1970; Vol. 12.
13. Brace, N. O.; Carpenter, B. L.; Shellhamer, D. F.; Daniels, M. J. Org. Chem. 1994, 59, 3670-3675. See supplementary material.
14. (a) Dannhardt, G. Arch. Pharm. (Weinheim, Ger.) 1978, 311-(4), 294; Chem. Abstr. 1978, 89, 42981p.
15. (a) Dannhardt, G. Arch. Pharm. (Weinheim, Ger.) 1978, 311-(4), 294; Chem. Abstr. 1978, 89, 42981p.
16. (b) Mazurkiewicz, R. Acad. Chim. Hung. 1984, 116(1), 95; Chem. Abstr. 1984, 101, 191663.
17. (b) Mazurkiewicz, R. Acad. Chim. Hung. 1984, 116(1), 95; Chem. Abstr. 1984, 101, 191663.
18. (c) Brozek, J.; Roda, J.; Kralecek, J. Makromol. Chem. 1988, 189, 1 - 7. Chem. Abstr. 1988, 108, 113081u.
19. (c) Brozek, J.; Roda, J.; Kralecek, J. Makromol. Chem. 1988, 189, 1 - 7. Chem. Abstr. 1988, 108, 113081u.
20. The MS spectra of substances 2, 3, 5, and 6 are given in the supplementary material of ref 9.
21. 7
22. Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry, Part A; Structure and Mechanisms; Plenum Press: New York, 1977; pp 158-160.
23. Lowry, T. H.; Richardson, K. S. Mechanism and Theory in Organic Chemistry, 2nd ed.; Harper and Row Publishers: New York, 1981.
24. (a) p 292;
25. (b) p 325;
26. (c) p 169.
27. 2O]. DMF:water mol ratios of 5-20 were used, with DMF:1 mol ratios of 10-40. Selectivity rose to 97% yield of alcohol and formate ester at the highest DMF:water mol ratio; a mol ratio of water:1 = 6 was used.
28. 2O]. DMF:water mol ratios of 5-20 were used, with DMF:1 mol ratios of 10-40. Selectivity rose to 97% yield of alcohol and formate ester at the highest DMF:water mol ratio; a mol ratio of water:1 = 6 was used.
29. -1.
30. Bredereck, H.; Gompper, R.; Theilig, G. Chem. Ber. 1954, 87, 537-546; and references therein.
31. Schwenk, U.; König, I.; Streitberger, A. U.S. Patent (to Hoechst Aktiengesellschaft, Fed. Rep. of Germany), August 26, 1980; Chem. Abstr. 1980, 93, 7656x.
32. Brace, N. O. Unpublished.
33. 3 and was characterized by elemental analyses (C,H,N), IR, and NMR.