Oxidative Cleavage of β-Keto Sulfones via Nitrous Acid

The reaction of nitrous acid with 1-aryl-2-(arylsulfonyl)ethanones 3a–e afforded the unexpected arenecarboxylic acids 12a–e, formic acid 14, and benzene/4-toluenesulfinic acid 15a, b through oxidative cleavage reaction. 4-Chlorobenzoic acid (12a), [1,1biphenyl]-4-carboxylic acid (12b), 2-naphthoic acid (12c), 2-thiophenecarboxylic acid (12d), and 2-benzofurancarboxylic acid (12e) were isolated in 72%, 62%, 55%, 58%, and 62% yields, respectively. The reported mechanistic pathways proposed the production of 1-aryl-2-(phenyl/tolylsulfonyl)ethane-1,2-dione 7 instead of arenecarboxylic acids 12. A mechanistic pathway to explain the reaction of nitrous acid with 1-aryl-2-(arylsulfonyl)ethanones 3a–e was suggested. In this pathway, the intermediate 1,2-oxazete 10 lost benzene/4-toluenesulfinic acid 15 to produce 1,2-oxazet-3-one 11. Ring cleavage of the latter intermediate afforded the arenecarboxylic acids 12.


Introduction
-Keto sulfones are versatile synthetic intermediates used for the preparation of diverse classes of organic compounds such as substituted acetylenes, olefins, allenes, vinyles, and pyrans.The chemistry of -keto sulfones achieved a significant peak of interest during the last decades and nowadays constitutes a whole branch of organosulfur chemistry [1][2][3].Although the chemistry of -keto sulfones has been widely investigated, little has appeared in the literature concerning their oximes.Oximes represent an important class of organic compounds with a wide range of practical applications.Oximes can be synthesized by condensation of an aldehyde or a ketone with hydroxylamine.They can also be obtained from reaction of nitrites with active methylene compounds.The latter reaction produces C-nitroso compounds which usually rearrange to oximino compounds.This reaction has value as a means of introducing an oximino function in a part of molecule that does not have a carbonyl group for direct oximation [4].The oxidation of oximes with various inorganic acids is a known procedure for the recovery of aldehydes and ketones from their corresponding oximes [5].This method has been widely utilized and its reaction mechanism has been reported [6].In this study and in continuation of our interest in chemistry of -keto sulfones [7][8][9], we shall deal with the reaction of nitrous acid with -keto sulfones 3 and therefore the probable modes of formation of the corresponding carboxylic acids 12.

Experimental
2.1.Chemistry 2.1.1.General.Melting points were determined on a Gallenkamp melting point apparatus and are uncorrected.Infrared (IR) spectra were recorded as KBr disks using the Perkin Elmer FT-IR Spectrum BX apparatus.NMR spectra were scanned in DMSO- 6 on a Bruker NMR spectrometer operating at 500 MHz for 1 H and 125 MHz for 13 C.Chemical shifts are expressed in -values (ppm) relative to TMS as an internal standard.Coupling constants (J) are expressed in Hz.D 2 O was added to confirm the exchangeable protons.The mass spectra were performed using a Varian MAT CH-5 spectrometer (70 eV).

Synthesis of Oximes 4a-f.
To a stirred cold solution of -keto sulfones 3a-f [10][11][12][13][14][15] (10 mmol) in glacial acetic acid (20 mL), sulfuric acid (1 mL, 50%) was added.Then cold solution of sodium nitrite (0.7 g, 10 mmol) in water (5 mL) was added dropwise with stirring at such a rate that the temperature remains in the range 0-5 ∘ C.Over a period of 30 min, a light blue solution of nitrous acid is produced.The mixture is stirred for extra 1 h at 25 ∘ C. The reaction mixture was poured into cold water and the solid product was filtered off, washed with water, and dried.Recrystallization from EtOH afforded 4a-f which were used without any further purification in the next step.

The Reaction of Nitrous Acid with 𝛽-Keto Sulfones 3a-e.
To a stirred cold solution of -keto sulfones 3a-e (10 mmol) or oximes 4a-e (10 mmol) in glacial acetic acid (30 mL), sulfuric acid (5 mL, 50%) was added.Then cold solution of sodium nitrite (2.1 g, 30 mmol) in water (10 mL) was added dropwise with stirring at such a rate that the temperature remains in the range 0-5 ∘ C.Over a period of 30 min, a light blue solution of nitrous acid is produced.The mixture is stirred for extra 48 h at 25 ∘ C. The solid that precipitated was collected, washed with water, and dried.Recrystallization from EtOH afforded the corresponding carboxylic acids 12a-e in 55-72% yield.Formic acid (14) and benzene/4toluenesulfinic acid 15 were detected in filtrate using chromatographic analyses.4-Chlorobenzoic acid (12a) was isolated in 65% yield by the reaction of 1-(4-chlorophenyl)-2-[(4methylphenyl)sulfonyl]ethanone (3f) instead of 3a.

Results and Discussion
-Keto sulfones 3a-e were synthesized by the reaction of 2-bromo-1-arylethanone 1a-e with the appropriate sodium arylsulfinate 2a, b according to the reported method [10][11][12][13][14][15].Treatment of -keto sulfones 3a-e with sodium nitrite, in acetic acid containing sulfuric acid, afforded the corresponding carboxylic acids 12a-e in addition to formic acid (14) and benzene/4-toluenesulfinic acid 15a, b (Figure 1).Interestingly, it was found that this method provides the possibility to prepare carboxylic acids through the formation of oximes 4a-e as intermediates followed by the oxidative cleavage process of C-C bond by nitrous acid under the application of mild reaction conditions.In general, normal ketones are not oxidized except under extremely hard conditions and give several products [21].
Mechanistic explanation has been reported for the reaction of nitrous acid and nitrosonium ion NO + with oximes by Kliegman and Barnes [6].They proposed two mechanistic pathways using 15 N nitrous acid to determine the reaction products.The intermediate product of the reaction of nitrous acid with oxime 4 is the iminoxyl cation 5 which can react in one of these two pathways  or B (Figure 2).
The nitrosating agent nitrous acid is formed in situ by the action of acetic or mineral acid on sodium nitrite and a further reaction takes place to give the nitrosonium ion NO + (Figure 2).The reported mechanistic pathways through hydrolysis of iminoxyl cation 5 to give hydroxy precursor 6 (pathway A) or through nitrosation of 5 to give intermediate 8 and then 1,2,3-oxadiazete 9 (pathway B) proposed the production of 1-aryl-2-(phenyl/tolylsulfonyl)ethane-1,2-dione 7 instead of arenecarboxylic acids 12 (Figure 2).
These results stimulate our interest to offer a mechanistic pathway (pathway C) to explain the formation of acids 12 as main reaction products through oxidative cleavage of -keto sulfone oximes 4, keeping in mind the formation of formic acid (14) and benzene/4-toluenesulfinic acid 15 (Figure 2).In this pathway, hydroxy precursor 6 cyclized to give the intermediate 1,2-oxazete 10 which lost benzene/4-toluenesulfinic acid 15 to produce 1,2-oxazet-3-one 11.Ring cleavage of the latter intermediate afforded the arenecarboxylic acids 12 and di-anion 13 [6] which reacted with water to give formic acid (14).

Conclusion
In conclusion, we studied the reaction of nitrous acid with -keto sulfones 3a-e, and we also proposed a mechanistic pathway to explain the formation of unexpected carboxylic acids 12a-e through the oxidative cleavage reaction.

Figure 2 :
Figure 2: The reported mechanistic pathways  and B [6] for the reaction of nitrous acid with oximes suggested the formation of sulfonyldiketone 7 during the reaction of nitrous acid with oxime 4. The proposed mechanistic pathway of the reaction of nitrous acid with -keto sulfones 3 through intermediate 1,2-oxazete 10, pathway C.