Thioxanthenes and Thioxanthones

Thioxanthenes and Thioxanthones. - Several possible metabolites of the neuroleptic chlorprothixene (241) have been synthesized for example, the geometric isomers of 3-, 4-, 6-, and 7-hydroxy- and -methoxy-derivatives. Lucanthrone (242 = H) is known to have anti-tumour properties, 

A high-temperature synthesis of thioxanthene from thiophenol and o-chloro-or o-bromo-toluene has been reported. Irradiation of the thiol esters (44 X = Cl, Br, I, or SOgMe Y = H) afforded the thioxanthone (45 Y = H) and p-tolyl disulphide. This rearrangement is believed to involve a 1,3-shift of the SCgHgMe group. When the dichloro-compound (44 X = Y = Cl) was irradiated, photosubstitution occurred, giving the sulphide (45 Y = p-Me-CgH4S) instead of the expected chloride (45 Y = Cl). The same product was 

Benzyne intermediates are probably involved in the ring-closure of 2-(or 3-) chloro-2 -(methylthio)benzophenones to thioxanthones. Xanthones were prepared analogously. Syntheses of several pharmacologically useful thioxan-thene derivatives have been described. Ceric ammonium nitrate oxidizes thioxanthene to thioxanthone.  

The conformational preferences of 9-alkylthioxanthenes and their. S-oxides have been investigated by n.m.r. techniques, including solvent shifts. The magnitude of the chemical shifts of the 9-protons in the xanthene and thioxanthene anions indicates that their central rings are paratropic.  

Solutions of 9,9-dialkyl-thioxanthene cation radicals have been prepared and their e.s.r. and n.m.r. spectra studied. The conformations of anion radicals derived from thioxanthene iSiS-dioxide and its 9-substituted derivatives have been investigated by e.s.r. techniques.  

---

An X-ray study of thioxanthone 10,10-dioxide (Figure 12) has established that the molecule is almost planar with a dihedral (fold) angle of 177°. The C-S-C bond angle of 105.2° is significant and the S-C bond lengths are comparable with those in thioxanthene and thioxanthone <1995JCX321>. 

Both thioxanthene and thioxanthone give a ca. 1 1 mixture of sulfoxide and sulfone in high overall conversion in a Ti02-mediated photocatalytic oxidation (Scheme 62) <1998JPH(114)213>. Thioxanthone is oxidized to either its sulfoxide or sulfone in high yields and with excellent selectivity by stoichiometric quantities of perfluoro-rfr-2,3-dialkyloxaziridines 324 at —40 °C (Equation 57) <1994JOC2762>. 

Table 3 presents the hyperfme splitting constants of some sulfur-containing aromatic radical anions. The series studied included the monoxides and dioxides of dibenzothio-phene 1, thioxanthene 2, thioxanthone 3, dibenzo[b,/] thiepin 4 and dithienothiophene dioxide 5. 

The reduction of thioxanthone with LiAlD4 and A1C13 yields 9D-thioxanthene (93%) mp 147-148 °C and similar treatment of thioxanthen-9-ol affords the 9D,9H-thioxanthene. Reaction of thioxanthone with PhLi and the usual aqueous work-up yields 9-phenylthioxanthen-9-ol from which the 9-phenyl-9D-thioxanthene and the corresponding 9H-derivative 356 were obtained. Reaction of 356 with -BuLi and C02 gives 9-phenylthioxanthene-9-carboxylic acid (Scheme 80) <1998JPH(113)53>. 

Other papers on thioxanthene derivatives deal with the methylation, on sulphur and sulphoxide-oxygen respectively, of thioxanthene and thio-xanthone sulphoxide, the Beckmann rearrangement of thioxanthone oxime, and the quantitative reduction of thioxanthene sulphoxide to thioxanthene with sodimn borohydride-cobalt chloride, a reagent which appears to be of fairly neral applicability. ... 

Purification and Characterization. The thioxanthene product is essentially pure as isolated. It may be recrystallized from an ethanol-chloroform mixture, if necessary. Weigh the product and calculate the percent yield. Determine the melting point of the material and compare it with the value reported in the literature. Obtain IR spectra of thioxanthone and thioxanthene and compare them to each other as well as to those given in the literature The Aldrich Library ofIR Spectra and/or SciFinder Scholar). 

The thioxanthene ligand is oxidized to thioxanthone and sulfone ligands, the ratio of which depends on the amount of KMn04 Eq. (37) ... 

Isolation of Oxidation Products. After oxygen absorption had ceased, or reached the desired value, the oxidates were poured into water. In many cases the reaction product could be removed by filtration in high yield. In this manner xanthone (m.p. 172-174°C.), was isolated from oxidations of xanthene or xanthen-9-ol thioxanthone (m.p. 208-210°C.), from thioxanthene acridine (m.p. 107-109°C.), from acridan anthracene (m.p. 216-217°C.), from 9,10-dihydroanthracene phenanthrene (m.p. 95-99°C.), from 9,10-dihydrophenanthrene pyrene (m.p. 151-152.5°C.) (recrystallized from benzene) from 1,2-dihydropyrene and 4-phenan-throic acid (m.p. 169-171 °C.) (recrystallized from ethanol) by chloroform extraction of the hydrolyzed and acidified oxidate of 4,5-methyl-enephenanthrene. 

The concept of a photo-release and report system has been realized with the 9-(2-methyl-l,3-dithien-2-yl)-9//-thioxanthen-9-ol tethered to a PAMAM dendrimer. Irradiation of the dendrimer system with a U-360 broadband filter results in cleavage of the dithienyl unit to generate, after hydrogen radical transfer, 2-methyl-l,3-dithiane and the tethered thioxanthone 630. The increased fluorescence of the latter confirms the successful photo cleavage. The system offers potential for the generation of high local concentrations of substituted dithianes in the vicinity of the dendrimer surface (Equation 209) <2005JA12458>. 

Thioxanthenes.—The method of synthesizing xanthones that was mentioned in the previous section has also been applied to the corresponding thioxanthones. A compound which was described as 9,10-diphenyl-10-thia-anthracene has been shown to contain mono-, di, and tri-phenylthioxanthene. ... 

Excess 1 M diborane in tetrahydrofuran added during 0.5 hr. to thioxanthone 5,5-dioxide oxime acetate, and allowed to stand 12 hrs. at room temp. 10-amino-thioxanthene 5,5-dioxide. Y 69%. F. e. s. P. Catsoulacos, J. Heterocyclic Chem. 4,645 (1967). 

Since the diaryl ketone is the light-absorbing species in bimolecular photoinitiator systems, the selection of the appropriate ketone determines the wavelength sensitivity of the system. Besides benzophenone and substituted benzophe-nones, 25-27, a variety of thioxanthones (9H-thioxanthen-9-ones) and substituted thioxanthones, 28-30, are also commonly used. 

Reviews have appeared on thiopyrans, thiopyrylium salts, and thio-chromanones and related compounds. Biological aspects of some thioxanthone drugs and other thiop3rran derivatives have been reviewed. Space limitations preclude citation of the patent literature, but it should be noted that many patents have appeared that are concerned with juvenile-hormone intermediates and with biologically active thioxanthene derivatives. 

---