1. Field of the Invention
This invention relates to a process for the manufacture of fluorescein compounds, in particular fluorescein (also known as Solvent Yellow 94 or D&C Yellow No.7) and 3,4,5,6-tetrachlorofluorescein. In one aspect, the invention relates to the manufacture of a fluorescein compound by condensing phthalic anhydride with an excess of resorcinol, the resorcinol being employed both as a reactant and as a solvent for the reaction. In another aspect, the invention relates to the use of recycled resorcinol as a reactant and as a solvent for the reaction.
2. Description of the Prior Art
The production of fluorescein compounds is well known in the art, and it involves generally the condensation of phthalic anhydride with resorcinol in the presence or absence of a condensing agent. Fluorescein was originally prepared by Baeyer by fusing suitable proportions of phthalic anhydride and resorcinol (Baeyer,Ber.,4,555, (1871)and Ann.,183,1-74, (1876). During the early twentieth century, Orndorff et.al. studied this process in considerable detail (Orndorff et.al. JACS, 36,680-725,(1914); JACS, 40,1235-57,(1918); and JACS, 49,1272-80(1927)), and concluded that the preparation of fluorescein compounds in higher and purer yields requires the use of a condensing agent such as zinc chloride, phosphorus pentoxide etc. (Orndorff and Hitch,JACS, 36,684-86,(1914)).
Improvements to the fluorescein preparation process that obviated the formation of a final hard, infusible mass and avoided local overheating and resultant production of by-products (low yield and purity) were disclosed in U.S. Pat. No. 1,931,049 to Woods, et al. and U.S. Pat. No. 1,965,842 to Kranz. The improvements involve the use of inert organic liquids as the solvent for the reaction mixture. Products prepared in this manner, however, are contaminated by new impurities. As such, the contaminants require essentially complete removal before the products can be used as FDA certified dyes or dye intermediates.