Improved Synthesis of Thiofluorescein

Abstract

Thiofluorescein was synthesized in a preparative yield by successive demethylation of 3,3'-dimethoxydiphenyl sulfide to 3,3'-dihydroxydiphenyl sulfide and condensation of the latter with phthalic anhydride in H 2 SO 4 . The title compound was also obtained in a higher yield from 3,3'-dimethoxydiphenyl sulfide directly in a one-pot process combining the condensation in H 2 SO 4 and demethylation in 2 Py · H 2 SO 4 .Bromo-and iodo-substituted xanthene dyes are used in photopolymerization processes [14] due to high yield of the triplet state which gives rise to effective electron transfer from the donor molecule with formation of free radicals. Analogous increase in the yield of the triplet excited state is attained by replacement of the ring oxygen atom in Fluorescein by sulfur (Thiofluorescein) [5].A reliable synthesis of Thiofluorescein (3',6'-dihydroxy-3H-spiro[2-benzofuran-1,9'-[9H]thioxanthen]-3-one) was reported for the first time in patent [6]. 3,3'-Dimethoxydiphenyl sulfide (I) obtained by reaction of sodium 3-methoxybenzenethiolate with 3-iodo-1-methoxybenzene was demethylated to 3,3'-dihydroxydiphenyl sulfide (II), and the latter was brought into condensation with phthalic anhydride in 80% sulfuric acid. However, neither the yield nor other parameters of the condensation product were given. According to Pfoertner [7], the condensation of sulfide II with phthalic anhydride was performed in molten ZnCl 2 , but no experimental procedure was given. Eltsov et al. [5] synthesized Thiofluorescein (III) using as starting compound sulfide I rather than II. The condensation and demethylation stages were combined into a onepot process which was carried out in 80% sulfuric acid. The target product was isolated in 32% yield after triple reprecipitation, washing, dissolution, filtration, and additional purification. The product was characterized only by the analytical data (C, H) and molar absorption coefficient in a sodium hydroxide solution.The goal of the present work was to experimentally check the above procedures for the synthesis of Thiofluorescein (III) and improve them using both methoxy sulfide I and hydroxy sulfide II as initial compound. The first stage in the synthesis of Thiofluorescein (III) is preparation of sulfides I and II. According to the data of [57], sulfide I was obtained by heating a mixture of sodium-3-methoxybenzenethiolate with 3-iodo-1-methoxy-benzene (Scheme 1) above 200°C in the presence of copper powder [8]. Our attempts to reproduce this procedure showed that the yield of sulfide I does not exceed 52%. Schopfer and Schlapback [9] proposed to use tris(dibenzylideneacetone)dipalladium Pd 2 (dba) 3 as efficient catalyst for analogous condensations. Under the conditions reported in [9] [100°C, Pd 2 (dba) 3 ], we synthesized sulfide I in 80% yield.Demethylation of I was effected [6,7] by treatment with hydrogen iodide in acetic acid. We applied a more 0H2 6+ , 20H 3G GED '3(SKRV W%X2. 3K0H R & K 6 0H2 20H , Scheme 1. Deceased.DPEphos is 2,2'-bis(diphenylphosphino)diphenyl ether.

Synthesis of new asymmetric xanthene dyes via catalyst-free SNAr with sulfur nucleophiles

“…32,33 As a further reference compound, DCFI carries two heavy atoms similar to sulfur, has a high quantum yield (Φ f = 0.86). 11 Although DCFl is frequently promoted as a photostable dye, its half-life under our conditions is only marginally better than that of Fl, while the best thioethers show half-life times increased by about an order of magnitude. These results were achieved under near-physiological conditions, i.e.…”

“…3,[7][8][9][10] In the particular case of thioxanthenes, the biarylether has also been formed in a separate reaction, which was then followed by condensation with a phthalic acid derivative. 11 Such stepwise reactions allow the controlled synthesis of xanthenes which are asymmetric with respect to the 3′/6′ positions. 12 A one-step synthesis with two different resorcinol or aminophenol derivatives also affords asymmetric xanthenes, but results in a complicated reaction mixture that requires separation of the several resulting xanthene dyes.…”

Development of a Selective Fluorescent Probe for Hypochlorous Acid Detection and Imaging

“…In recent years, thiol‐containing compounds have been found to be responsible to ROS, e.g., HOCl . Inspired by this, TF was chosen in this study owing to its advantages of simple synthesis, large Stokes shift, long emission wavelength and so on.…”