Preparation of Acrylophenones and 2-Alkyl Indanones Utilizing Hexamethylenetetramine as an Inexpensive Mannich Reagent.

REFERENCES

• U. S. Pat. . 4,587,357 . U. S. Pat. 4,605,706 assigned to Merck & Co.
   Google Scholar
• EP 9554 assigned to Schering AG
   Google Scholar
• US. Pat. . 4,022,386 . US. Pat. 4,064,272; US. Pat. 4,117,012; US. Pat. 4,164,514 assigned to Pfizer Inc.
   Google Scholar
• U.S. Pat. . 4,322,437 . BE 854567 assigned to Sandoz
   Google Scholar
• Zacchei , A. G. , Dobrinska , M. R. , Wilshouky , T. I. , Kwan , K. C. and White , S. D. 1982 . Drug Met. and Disp. , 10 : 20
   PubMed Web of Science ®Google Scholar
• Jane de Solms , S. 1976 . J. Org. Chem. , 41 : 2650
   Web of Science ®Google Scholar
• Cragoe , E. J. Jr , Schultz , E. M. , Schneeberg , G. E. , Stocker , O. W. , Woltersdorf Jr. , Fenetti , G. M. and Watson , L. S. 1975 . J. Med. Chem. , 18 : 225
   PubMed Web of Science ®Google Scholar
• U. S. Pat. . 3,483,227 . 1969 .
   Google Scholar
• U. S. Pat. . 4,316,043 . 1982 .
   Google Scholar
• (e) Cost of ([CH3)2N]2CH2) is $264/Kg for 100 Kg lots available from TCI America.
   Google Scholar
• Schultz , E. M. , Cragoe , E. J. Jr. , Blocking , J. B. , Bolhofer , W. A. and Sprague , J. M. 1962 . J. Med. Pharm. Chem. , 5 : 660
   PubMedGoogle Scholar
• Tramontini , M. 1973 . Synthesis , : 703
   Web of Science ®Google Scholar
• Tramontini , M. and Angionlini , L . 1990 . Tetrahedron , 46 : 1791
   Web of Science ®Google Scholar
• Burckhalter , J. H. and Reynold , C. R. 1948 . J. Am. Chem. Soc. , 70 : 4184
   PubMed Web of Science ®Google Scholar
• Grebenyuk , A. D. , Shaipova and Zh , N. 1976 . J. Org. Chem. U.S.S.R. (Engl. Transl.) , 12 : 1502
   Google Scholar
• Pinnick , H. W. , Brown , S. P. , Mclean , E. A. and Zoller , L W. 1981 . J. Org. Chem. , 46 : 3758
   Web of Science ®Google Scholar
• Morriconi , E. J. and Creegan , R. J. 1966 . J. Org. Chem. , 31 : 2090
   Web of Science ®Google Scholar
• 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).
   Google Scholar
• Cost 40oS / Ib for commercial quantities (Chemical Marketing Reporter, May 1, 1995).
   Google Scholar
• The HMTA/Ac2O-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.
   Google Scholar
• 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.
   Google Scholar
• (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.
   Google Scholar
• Hofmann , A. W. 1881 . Ber , 14 : 2725 (For review, see Cope; Trumbull. Org. React, 1960, 11: 317)
   Google Scholar
• Angyl , S. J. 1954 . Org. React. , 8 : 197
   Google Scholar
• A finite concentration of the enolate anion would be present by the action of HMTA on the aryl alkyl ketone.
   Google Scholar
• The olefination which was performed neat without any solvent is also environmentally attractive.
   Google Scholar
• Ellis , G. P. and Barker , G. 1972 . Prog. Med. Chem. , 9 : 65
   PubMedGoogle Scholar