Thioxanthen-9-one as a Versatile Reagent

Thioxanthen-9-one is a reagent and a starting material for the synthesis of Metixene Hydrochloride. It is also used for highly functional group tolerant and chemoselective oxidation of aromatic or aliphatic sulfides to sulfoxides with hydrogen peroxide.

Aryl esterification using a triplet photosensitiser thioxanthen-9-one

Aryl esters are commonly encountered in natural products, agrochemicals, pharmaceuticals, polymers and arylating reagents. They are typically made by the condensation of phenols with carboxylic acids or their derivatives. Over the years, metal-catalyzed arylative coupling using carboxylic acids as the O-nucleophile has become an important alternative route. Ketones have been used as triplet photosensitizers for [2 + 2] cycloaddition reactions, generation of singlet oxygen, deracemization of chiral allenes, and atom-transfer radical additions. In the present work, we have employed commercially available, inexpensive thioxanthen-9-one (TXO) as an energy transfer photosensitizer to promote the nickel-catalyzed esterification of carboxylic acids with aryl bromides under the irradiation of visible light. This methodology proved to be applicable to various carboxylic acids and aryl bromides. The corresponding aryl esters were obtained in moderate to excellent yields. We prepared aryl-nickel(ii) acetate species (dtbbpy)-2,6-bis(trifluoromethyl)phenylnickel(ii) acetate (4) to study the mechanism of esterification. Cyclic voltammogram (CV) measurements of 4 and TXO revealed that E1/2 was 0.972 V vs. saturated calomel electrode (SCE) in DMSO and −1.700 V vs. SCE in MeCN. The excited-state redox potential of Thioxanthen-9-one was estimated to be 1.280 V vs. SCE based on both the electrochemical and spectroscopic data. One electron could potentially transfer from 4 to TXO*, yielding TXO˙− and (dtbbpy)-2,6-bis(trifluoromethyl)phenylnickel(iii) acetate.[1]

The irradiation of (dtbbpy)-4-cyanophenylnickel(ii) bromide and CsOAc with Thioxanthen-9-one in DMSO under visible light for 24 h led to the formation of 4-cyanophenyl acetate (3av) in 81% yield. In the absence of photosensitizer, the DMSO solution of (dtbbpy)-4-cyanophenylnickel(ii) bromide and CsOAc afforded 3av in 15% yield after the 120 h irradiation (eqn (2)). A mechanism involving triplet energy transfer from the excited-stated photosensitizer to (dtbbpy)-arylnickel(ii) carboxylate intermediate might therefore be operative. This mechanism would also be consistent with the stoichiometric experiments. Photosensitizers CF3-TXO and Cl-TXO possess lower triplet state energies than does Thioxanthen-9-one, which is confirmed by their longer emission wavelengths. Moreover, there is considerable overlap between the emission of TXO and the absorbance of 4. These results suggest that energy transfer likely plays a key role in the reductive elimination step. To summarize, we have developed one methodology for visible light driven, nickel-catalyzed esterification of carboxylic acids with aryl bromides to provide aryl esters using thioxanthen-9-one as an energy transfer photosensitizer. This transformation likely proceeds through the oxidative addition of an aryl bromide to nickel(0), the transmetalation of aryl–Ni(ii) bromide to generate an aryl–Ni(ii) carboxylate, energy transfer from the excited-state thioxanthen-9-one to the aryl–Ni(ii) carboxylate and finally reductive elimination to yield an aryl ester.

Mechanism of the reduction of different thioxanthen-9-ones

The exact mechanism of action of these compounds is unknown; however, some members of this family of compounds preferentially inhibit DNA synthesis and mammalian topoisomerase type II. Presumably, thioxanthen-9-ones during such processes undergo reduction into thioxanthenes. The use of thioxanthenones as sensitizers in production of inks shows another possible application of these compounds. For example, 1-chloro-4-propoxythioxanthen-9-one (Green & Timms, Citation1993; Green, Timms, & Green, Citation1991) exhibits higher activity when compared to 4-isopropylthioxanthenone, which is generally regarded as the industrial standard for these systems. In fact, thioxanthen-9-one photosensitizer initiates polymerization of vinyl monomers during such processes.[2]

We were presently anxious to suggest a definite mechanism of reduction of studied thioxanthen-9-one. In the purpose to choose or exclude the mechanism involving formation of ketyl radical during such reduction, we have reduced thioxanthen-9-one to thioxanthen-9-ol using LiAlH4. Further azeotropic dehydration in benzene of a mixture of thioxanthen-9-ol with bis(tributyltin) oxide gave 9-tributylstannyloxythioxanthen. Its reduction with Bu2SnClH led directly to thioxanthene. It seems to indicate the formation of the ketyl radical as an intermediate product, similarly as it has been reported by Yates and Schuster (Citation1984) during photoreduction of thioxanthenones.

References

[1] Zhu, D.-L., Li, H.-X., Xu, Z.-M., Li, H.-Y., Young, D. J., & Lang, J.-P. (2019). Visible light driven, nickel-catalyzed aryl esterification using a triplet photosensitiser thioxanthen-9-one†. Organic Chemistry Frontiers, 14, 2353–2359.

[2] A. Kosińska,   W. K. (2015). Studies of the mechanism of the reduction of different thioxanthen-9-ones. Cogent Chemistry, 1 1.