1. Field of the Invention
The present invention relates to process for the production of 2-substituted-9-hydroxy-1-oxo-1H-naphtho[2,1-b]pyrans and 2-substituted-9-acetoxy-1-oxo-1H-naphtho[2,1-b]pyrans and the compounds produced thereby.
2. Disclosure of the Prior Art
Structurally distinct gamma-pyrone-3-carboxaldehyde derivatives are disclosed in the following United States patents: U.S. Pat. No. 3,887,585 and a division thereof, U.S. Pat. No. 3,959,480; U.S. Pat. No. 3,862,144 and a division thereof, U.S. Pat. No. 3,936,488; and U.S. Pat. No. 3,886,183. The fusion between the pyran ring and the naphthalene ring in certain of the compounds disclosed in aforementioned patents occurs at the [1,2-b] position or at the [2,3-b] position. If the compounds of the subject invention, this fusion is at the [2,1-b] position. Thus structurally distinct chemical compounds are provided.
Naphthodioxaborin intermediates are also disclosed in aforementioned United States patents which are structurally distinct from the naphthodioxaborin intermediate of the subject invention, since a corresponding difference in ring fusion is present.
Additionally, processes are described in aforementioned United States patents for obtaining the naphthodioxaborin intermediates and the gamma-pyrone-3-carboxaldehyde derivatives disclosed. However, no processes are disclosed in these patents for obtaining the structurally distinct compounds of the subject invention.
G. A. Reynolds and J. A. Van Allan, in J. Het. Chem. 6:375-377 (June, 1969) disclose an unsubstituted 3-formyl-benzo[f]chrom-4-one (designated compound 10) which has the same ring system as the final compounds of the subject invention. Also disclosed is an unsubstituted naphthodioxaborin intermediate (designated compound 4) from which compound 10 is prepared. In an earlier paper by these same authors (Van Allan, J. A. and Reynolds, G. A., J. Het. Chem. 6:29-35 (February, 1969)), the preparation of the unsubstituted naphthodioxaborin intermediate (designated compound 1) is described: .beta.-naphthol and boran trifluoride acetic acid are heated together to obtain the desired naphthodioxaborin.
U.S. Pat. No. 3,896,114 discloses benzo[f]chromones having a formyl, cyano or tetrazole group in the three position, but without substituents on the phenyl ring. West German Application No. 25 23 194 discloses certain 3-ring chromone derivatives having an acid, ester, amide, cyano or tetrazole substituent on the 3-position, among which there is mentioned trans-3-(8-methoxycarbonyl-4-oxo-4,6,7,8-tetrahydro-cyclopenta[g]-1-benzop yran-3-yl)acrylic acid.
Two-ring chromone structures having various substitutents at the two or three position are also known in the art. For example, U.S. Pat. No. 3,912,760 discloses chromone-3-carboxaldehydes; U.S. Pat. No. 3,849,446 discloses chrmone-3-carboxylic acids; U.S. Pat. No. 3,872,108 discloses chromone-3-acrylic acids; and U.S. Pat. No. 3,862,143 discloses chromone-3-carbonitriles and chromone-3-carboxylic acids.
Based on the previously mentioned work of Reynolds and Van Allan (J. Het. Chem. 6:29-35 February, 1969 and 6:375-377 June, 1969), reaction of 2,7-dihydroxynaphthalene with acetic acid and boron trifluoride etherate would be expected to yield a dioxaborin ring on each of the hydroxy groups in the starting material, thus providing a bis(dioxaborin)naphthalene structure (designated Compound 3 in the reaction scheme of the subject invention). However, quite surprisingly, it has now been found that a naphthodioxaborin having an acetoxy substituent is obtained: 3,3-difluoro-1-methylnaphtho[2,1-d],3,3-dioxaborin-9-ol acetate, designated Compound 2 in the reaction scheme of the subject invention. Compound 2 has been found to be a valuable intermediate for the synthesis of antiallergy agents.
USPTO Backgrounds
USPTO Backgrounds