Preparation of acrylophenones and 2-alkyl indanones utilizing hexamethylenetetramine as an inexpensive Mannich reagent

Synthetic Communications

Volumn 26, Issue 9, 1996, Pages 1775-1784

  Bhattacharya, Apurba ^a   Segmuller, Brigitte ^a   Ybarra, Arnold ^a  

^a Hoechst Celanese Corporation   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INDANONE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS; TECHNIQUE;

EID: 0029884284     PISSN: 00397911     EISSN: None     Source Type: Journal    
DOI: 10.1080/00397919608002617     Document Type: Article

References (28)

1. (a) U. S. Pat. 4,587,357; U. S. Pat. 4,605,706 assigned to Merck & Co.
2. (b) EP 9554 assigned to Schering AG.
3. (c) U.S. Pat. 4,022,386; U.S. Pat. 4,064,272; U.S. Pat. 4,117,012; U.S. Pat. 4,164,514 assigned to Pfizer Inc.
4. (d) U.S. Pat. 4,322,437; BE 854567 assigned to Sandoz.
5. (e) Zacchei, A. G.; Dobrinska, M. R.; Wilshouky, T. I.; Kwan, K. C.; White, S. D.; Drug Met and Disp. 1982, 10, 20
6. (a) Jane deSolms, S. J. Org. Chem. 1976, 41, 2650.
7. (b) Cragoe, E. J. Jr.; Schultz, E. M.; Schneeberg, G. E.; Stocker, O. W.; Woltersdorf, Jr., Fenetti, G. M.; Watson, L. S. J. Med. Chem., 1975, 18, 225.
8. (c) U. S. Pat. 3,483,227 (1969).
9. (d) U. S. Pat. 4,316,043 (1982).
10. 2) is $264/Kg for 100 Kg lots available from TCI America.
11. (a) Schultz, E. M.; Cragoe, E. J.Jr.; Blocking, J. B.; Bolhofer, W. A.; Sprague, J. M. J. Med. Pharm. Chem., 1962, 5, 660.
12. (b) Tramontini, M. Synthesis, 1973, 703.
13. (c) Tramontini, M.; Angionlini, L. Tetrahedron, 1990, 46, 1791.
14. (d) Burckhalter, J. H.; Reynold, C. F.; J. Am. Chem. Soc., 1948, 70, 4184.
15. (e) Grebenyuk, A. D.; Shaipova, N. Zh. J. Org. Chem. U.S.S.R. (Engl. Transl.), 1976, 12, 1502.
16. (f) Pinnick, H. W.; Brown, S. P.; McIean, E. A.; Zoller, L. W. J. Org. Chem., 1981, 46, 3758.
17. (g) Morriconi, E. J.; Creegan, F. J. J. Org. Chem., 1966, 31, 2090.
18. (a) Hexamethylenetetramine, readily obtainable from ammonia and formaldehyde, is a stable reagent with an adamantane-like structure. Hexamethylenetetramine has been widely used for the introduction of the formyl group and amino group (Sommelet reaction and Duff reaction) in aromatic compounds. (For review, see Synthesis., 1979, 161).
19. (b) Cost 40¢ / Ib for commercial quantities (Chemical Marketing Reporter, May 1, 1995).
20. 2O-mediated methylenation is limited to the preparation of 2-alkyl indanones. Thus simple acetophenone fails to undergo methylenation under the reaction conditions presumably due to lack of enolization of the substrate.
21. (d) Electron poor aryl alkyl ketones, although undergoes facile methylenation, fails to cyclize under acidic conditions to the indanones due to deactivation of the aromatic ring e.g. equation presented
22. (a) A mixture (60:40) of the two regioisomeric cyclized products (6-bromo and the 4-bromo) was obtained; the ratio was verified by C-H correlation and quantitative 13C NMR experiments.
23. (a) Hofmann, A. W. Ber., 1881, 14, 2725. (For review, see Cope; Trumbull.Org. React, 1960, 11,317).
24. (a) Hofmann, A. W. Ber., 1881, 14, 2725. (For review, see Cope; Trumbull.Org. React, 1960, 11,317).
25. (b) Angyl, S. J. Org. React. 1954, 8, pp 197.
26. (c) A finite concentration of the enolate anion would be present by the action of HMTA on the aryl alkyl ketone.
27. The olefination which was performed neat without any solvent is also environmentally attractive.
28. Ellis, G. P.; Barker, G. Prog. Med. Chem., 1972, 9, 65.