Oxidative Cleavage of <b><i>β</i></b>-Keto Sulfones via Nitrous Acid

Abdel-Aziz, Hatem A.

doi:https://doi.org/10.1155/2014/524930

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Research Article | Open Access

Volume 2014 | Article ID 524930 | https://doi.org/10.1155/2014/524930

Oxidative Cleavage of β-Keto Sulfones via Nitrous Acid

Hatem A. Abdel-Aziz^1,2

Academic Editor: Gustavo Portalone

Received27 Oct 2014

Accepted29 Nov 2014

Published15 Dec 2014

Abstract

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), [1,1′-biphenyl]-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.

1. Introduction

β-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 β-keto sulfones achieved a significant peak of interest during the last decades and nowadays constitutes a whole branch of organosulfur chemistry [1–3]. Although the chemistry of β-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 β-keto sulfones [7–9], we shall deal with the reaction of nitrous acid with β-keto sulfones 3 and therefore the probable modes of formation of the corresponding carboxylic acids 12.

2. 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- on a Bruker NMR spectrometer operating at 500 MHz for ¹H and 125 MHz for ¹³C. Chemical shifts are expressed in δ-values (ppm) relative to TMS as an internal standard. Coupling constants (J) are expressed in Hz. D₂O was added to confirm the exchangeable protons. The mass spectra were performed using a Varian MAT CH-5 spectrometer (70 eV).

2.1.2. Synthesis of 1-Aryl-2-arylsulfonyl Ethanones 3a–f

These compounds were prepared according to the reported method [10–15].

2.1.3. Synthesis of Oximes 4a–f

To a stirred cold solution of β-keto sulfones 3a–f [10–15] (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.

2.1.4. The Reaction of Nitrous Acid with β-Keto Sulfones 3a–e

To a stirred cold solution of β-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/4-toluenesulfinic 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-[(4-methylphenyl)sulfonyl]ethanone (3f) instead of 3a.

(1) 4-Chlorobenzoic Acid (12a). This acid was prepared from 1-(4-chlorophenyl)-2-(phenylsulfonyl)ethanone (3a) [10] in 65% yield (1.02 g). 1-(4-Chlorophenyl)-2-[(4-methylphenyl)sulfonyl]ethanone (3f) [11] afforded 1.13 g (72% yield) of 4-chlorobenzoic acid (12a); m.p. 238–240°C (Let. m.p. 238–241°C) [16]; ¹H NMR δ 7.57 (d, J = 8.5 Hz, 2H, ArHs), 7.95 (d, J = 8.5 Hz, 2H, ArHs), 13.20 (s, D₂O exchangeable, 1H, OH); ¹³C NMR δ 128.69 (C3 and C5), 129.72 (C1), 131.10 (C2 and C6), 137.70 (C4), 166.45 (C=O); MS (EI) m/z 156 [M⁺], 157 [M⁺+1], 158 [M⁺+2].

(2) [1,1-Biphenyl]-4-carboxylic Acid (12b). This acid was prepared from 1-(1,1′-biphenyl-4-yl)-2-(phenylsulfonyl)ethanone (3b) [12] in 62% yield (1.23 g); m.p. 225–227°C (Let. m.p. 220–225°C) [17]; ¹H NMR δ 7.43 (t, J = 7.5 Hz, 1H, ArH), 7.51 (t, J = 7.5 Hz, 2H, ArHs), 7.75 (d, J = 7.5 Hz, 2H, ArHs), 7.79 (d, J = 8.5 Hz, 2H, ArHs), 8.03 (d, J = 8.5 Hz, 2H, ArHs), 13.00 (s, D₂O exchangeable, 1H, OH); ¹³C NMR δ 126.70 (C3 and C5), 126.91 (C2 and C6), 128.20 (C4 and C4′), 129.04 (C3′ and C5′), 129.90 (C2′ and C6′), 139.07 (C1′), 144.0 (C1), 167.26 (C=O); MS (EI) m/z 198 [M⁺].

(3) 2-Naphthoic Acid (12c). This acid was prepared from 2-[(4-methylphenyl)sulfonyl]-1-(2-naphthalenyl)ethanone (3c) [13] in 55% yield (0.95 g); m.p. 186–188°C (Let. m.p. 185–187°C) [18]; ¹H NMR δ 7.60–7.68 (m, 2H, ArHs), 7.98–8.03 (m, 3H, ArHs), 8.21 (d, J = 8.0 Hz, 1H, ArH), 8.62 (s, 1H, ArH), 13.11 (s, D₂O exchangeable, 1H, OH); ¹³C NMR δ 125.25 (C3), 126.69 (C2), 127.60 (C7), 128.01 (C5), 128.14 (C4), 128.63 (C6), 129.20 (C8), 130.34 (C1), 132.14 (C8a), 134.80 (C4a), 167.56 (C=O); MS (EI) m/z 172 [M⁺].

(4) 2-Thiophenecarboxylic Acid (12d). This acid was prepared from 2-[(4-methylphenyl)sulfonyl]-1-(2-thienyl)ethanone (3d) [14] in 58% yield (0.74 g); m.p. 124–126°C (Let. m.p. 125–127°C) [19]; ¹H NMR δ 7.19 (dd, J = 3.5, 4.8 Hz, 1H, H4), 7.727 (dd, J = 0.7, 3.5 Hz, 1H, H5), 7.91 (dd, J = 0.7, 4.8 Hz, 1H, H3), 13.23 (s, D₂O exchangeable, 1H, OH); ¹³C NMR δ 135.20 (C2), 133.79 (C3), 128.82 (C4), 133.81 (C5), 163.51 (C=O); MS (EI) m/z 128 [M⁺].

(5) 2-Benzofurancarboxylic Acid (12e). This acid was synthesized from 1-(2-benzofuranyl)-2-(phenylsulfonyl)ethanone (3e) [15] in 52% yield (0.84 g); m.p. 193–195°C (Let. m.p. 193–196°C) [20]; ¹H NMR δ 7.38 (t, J = 7.5 Hz, 1H, H5), 7.53 (t, J = 7.5 Hz, 1H, H4), 7.71–7.77 (m, 2H, H3+H4), 7.83 (d, J = 7.5 Hz, 1H, H6), 13.80 (s, D₂O exchangeable, 1H, OH); ¹³C NMR δ 114.35 (C8), 115.82 (C3), 123.00 (C4), 123.91 (C5), 127.04 (C6), 127.84 (C3a), 146.02 (C2), 154.95 (C8a), 160.02 (C=O); MS (EI) m/z 162 [M⁺].

3. Results and Discussion

β-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 [10–15]. Treatment of β-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].

4-Chlorobenzoic acid (12a), [1,1′-biphenyl]-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, by the reaction of β-keto sulfones 3a–e with excess nitrous acid at 0–5°C. 4-Chlorobenzoic acid (12a) was isolated in 65% yield by the reaction of 1-(4-chlorophenyl)-2-[(4-methylphenyl)sulfonyl]ethanone (3f) instead of 3a. The structures of carboxylic acids 12a–e are assigned on the basis of their spectral data and physical constants which are identical with those described for authentic samples of 12a–e obtained commercially [16–20]. For example, ¹H NMR of acids 12a–e revealed the D₂O exchangeable signal of carboxylic OH in the region δ 13.0–13.8 whereas their ¹³C NMR showed the signal due to the carbon of carbonyl function in the region δ 160.2–167.56. ¹H NMR of 12a showed the AB system of Para substituted benzene ring at δ 7.57 and 7.95 as two doublets with J = 8.5 Hz, whereas the ¹H NMR of 15d revealed three doublets of doublets (dd) signals at δ 7.19 (J = 3.5, 4.8 Hz), 7.727 (J = 0.7, 3.5 Hz), and 7.91 (J = 0.7, 4.8 Hz) for H4, H5, and H3 of thiophene moiety, respectively.

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 ¹⁵N 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 (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 β-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).

4. Conclusion

In conclusion, we studied the reaction of nitrous acid with β-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.

Conflict of Interests

The author has declared that there is no conflict of interests.

Acknowledgment

The author would like to extend his sincere appreciation to the Deanship of Scientific Research at King Saud University for its funding of this research through the Research Group Project no. RGP-VPP-321.

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Copyright

Copyright © 2014 Hatem A. Abdel-Aziz. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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