The production of isochromans has been shown in the art and certain novel isochromans have recently been disclosed with an outstanding musk fragrance. Such isochromans especially adapted for perfumery by virtue of their fragrance properties have been disclosed in Heeringa & Beets U.S. Pat. No. 3,360,530, issued on Dec. 26, 1967.
A number of routes are available for the production of isochromans, such as those set forth in U.S. Pat. No. 3,360,530 and one of the most straightforward of these routes is treatment of a Friedel-Crafts reactant with an alkylene oxide under Friedel-Crafts conditions to form an aryl alkanol. The aryl alkanol is then isolated and thereaffter reacted with formaldehyde to cyclialkylate the alcohol. The efficiency of this multistage process leaves much to be desired because of yield impairment due to the large amount of working required.
U.S. Pat. No. 3,532,719 set forth a process for producing such isochromans which solved a number of the problems of the processes set forth in U.S. Pat. No. 3,360,530. U.S. Pat. No. 3,532,719 provided a more simplified and more economical process for producing isochromans which comprises reacting a Friedel-Crafts reactant with an alkylene oxide in the presence of aluminum chloride to form an aryl alkanol, partially deactivating the aluminum chloride after formation of the aryl alkanol, and cyclialkylating the aryl alkanol with formaldehyde in the presence of the partially deactivated aluminum chloride to form the isochroman, The disadvantage of such procedures for the preparation of isochromans is in the second step wherein chloromethyl methyl ethers may be involved which have been reported to be health hazards and accordingly special precautions are required when handling. The preparation and use of such chloromethyl methyl ethers and the use of aluminum chloride complexes give rise to the release of hydrogen chloride vapors and formation of aqueous hydrogen chloride solutions requires the use of more expensive glass lined vessels due to the more corrosive mixtures in the reaction.
Steyn and Holzapfel, Tetrahedron, 23, 4449 (1967), reports the reaction of a halo aryl alkanol with chloromethyl methyl ether and zinc chloride to give an isochroman according to the following reaction: ##SPC3##
Meyer and Turner, Tetrahedron, 27, 2609, (1971), reports the reaction of a methoxy aryl alkanol with sodium hydride and chloromethyl methyl ether to give a methoxy aryl alkanol methyl ether. Subsequent treatment of the methoxy aryl alkanol methyl ether with toluenesulfonic acid is indicated to yield isochromans according to the following reaction: ##SPC4##
USPTO Backgrounds
USPTO Backgrounds