Oxidative Cleavage of β -Keto Sulfones via Nitrous Acid

Article abstract of DOI:10.1155/2014/524930

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.

Full text of DOI:10.1155/2014/524930

Hindawi Publishing Corporation
Journal of Chemistry
Volume 2014, Article ID 524930, 4 pages
http://dx.doi.org/10.1155/2014/524930
Research Article
Oxidative Cleavage of ꢀ-Keto Sulfones via Nitrous Acid
Hatem A. Abdel-Aziz1,2
1Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
2Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo 12622, Egypt
Correspondence should be addressed to Hatem A. Abdel-Aziz; hatem 741@yahoo.com
Received 27 October 2014; Accepted 29 November 2014; Published 15 December 2014
Academic Editor: Gustavo Portalone
Copyright © 2014 Hatem A. Abdel-Aziz. is 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.
e 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), [1,1ꢀ-
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. e 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
of ꢀ-keto sulfones [7–9], 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.
ꢀ-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.
e chemistry of ꢀ-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 ꢀ-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. ey can also be obtained from reaction of
nitrites with active methylene compounds. e latter reaction
produces C-nitroso compounds which usually rearrange to
oximino compounds. is 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]. e
oxidation of oximes with various inorganic acids is a known
procedure for the recovery of aldehydes and ketones from
their corresponding oximes [5]. is method has been widely
utilized and its reaction mechanism has been reported [6]. In
this study and in continuation of our interest in chemistry
2. Experimental
2.1. Chemistry
2.1.1. General. Melting points were determined on a Gal-
lenkamp 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 1H and 125 MHz for 13C. Chemical
shifs are expressed in ꢂ-values (ppm) relative to TMS as an
internal standard. Coupling constants (J) are expressed in
Hz. D O was added to confirm the exchangeable protons.
2
e 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. ese
compounds were prepared according to the reported method
[10–15].

2
Journal of Chemistry
O
O
O
Ar1-SO2Na
2a, b
O
O
O
O
S
HNO2
Ar1
Ar
Br
S
Ar1
Ar
Ar
1a–e
NOH
3a–e
4a–e
Ar1
Ar
HNO2
H2O
OH
a
b
c
d
e
4-Chlorophenyl
1,1ꢀ-Biphenyl-4-yl
2-Naphthalenyl
2-ienyl
Phenyl
Phenyl
4-Tolyl
4-Tolyl
Phenyl
O
O
+
N2O
+
+
Ar1-SO2 -H
C
2-Benzofuranyl
Ar
OH
H
12a–e
14
15a, b
COOH
COOH
COOH
COOH
COOH
O
S
Cl
12a
12d
12b
12c
12e
Figure 1: e reaction of nitrous acid with ꢀ-keto sulfones 3a–e.
1
2.1.3. Synthesis of Oximes 4a–f. To a stirred cold solution
of ꢀ-keto sulfones 3a–f [10–15] (10 mmol) in glacial acetic
acid (20 mL), sulfuric acid (1 mL, 50%) was added. en 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. e
mixture is stirred for extra 1 h at 25∘C. e 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.
238–241∘C) [16]; H NMR ꢁ 7.57 (d, J = 8.5 Hz, 2H, ArHs),
7.95 (d, J = 8.5 Hz, 2H, ArHs), 13.20 (s, D O exchangeable, 1H,
2
OH); 13C NMR ꢁ 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). is acid was
prepared from 1-(1,1ꢀ-biphenyl-4-yl)-2-(phenylsulfonyl)etha-
none (3b) [12] in 62% yield (1.23 g); m.p. 225–227∘C (Let. m.p.
220–225∘C) [17]; 1H NMR ꢁ 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,
D O exchangeable, 1H, OH); 13C NMR ꢁ 126.70 (C3 and C5),
2
126.91 (C2 and C6), 128.20 (C4 and C4ꢀ), 129.04 (C3ꢀ and C5ꢀ),
129.90 (C2ꢀ and C6ꢀ), 139.07 (C1ꢀ), 144.0 (C1), 167.26 (C=O);
MS (EI) m/z 198 [M+].
2.1.4. e Reaction of Nitrous Acid with ꢀ-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. en 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. e mixture
is stirred for extra 48 h at 25∘C. e 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 chro-
matographic analyses. 4-Chlorobenzoic acid (12a) was iso-
lated in 65% yield by the reaction of 1-(4-chlorophenyl)-2-[(4-
methylphenyl)sulfonyl]ethanone (3f) instead of 3a.
(3) 2-Naphthoic Acid (12c). is 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–
1
187∘C) [18]; H NMR ꢁ 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, D O exchangeable, 1H, OH); 13C NMR ꢁ 125.25 (C3),
2
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-iophenecarboxylic Acid (12d). is acid was pre-
pared from 2-[(4-methylphenyl)sulfonyl]-1-(2-thienyl)etha-
none (3d) [14] in 58% yield (0.74 g); m.p. 124–126∘C (Let. m.p.
125–127∘C) [19]; 1H NMR ꢁ 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,
(1) 4-Chlorobenzoic Acid (12a). is acid was prepared
from 1-(4-chlorophenyl)-2-(phenylsulfonyl)ethanone (3a)
[10] in 65% yield (1.02 g). 1-(4-Chlorophenyl)-2-[(4-methyl-
phenyl)sulfonyl]ethanone (3f) [11] afforded 1.13 g (72% yield)
of 4-chlorobenzoic acid (12a); m.p. 238–240∘C (Let. m.p.
H3), 13.23 (s, D O exchangeable, 1H, OH); 13C NMR ꢁ 135.20
2
(C2), 133.79 (C3), 128.82 (C4), 133.81 (C5), 163.51 (C=O); MS
(EI) m/z 128 [M+].

Journal of Chemistry
3
+
NO+ H2O
H2NO2
H+
+
+
HNO2
O
O
O
O
O
O
Ar1
S
S
Ar1
Ar
O
N
Ar
ONO
+
+
7
N2O +
NH3OH2
+N
ONO
+N
O
N
NO+
Pathway B
9
8
O
O
O
O
O
O
O
O
O
S
NO+
Ar1
H
S
S
Ar1
Pathway A
H2O/−H+
Ar
Ar1
Ar
N2O
+
H2O
Ar
+
4
O
N
+N
N
O
7
O
O
H
O
N
HO
5
6
O
C
H
OH
H
H
O
H2O
O
14
O
O
Ar1-SO2-H
15
O
S
O
Ar1
Ar
Ar
Pathway C
⌉
⌈
Ar
⌈
⌉
C = O
+
+
N2O
OH
6
O
N
H
O
O
N
O
N
12
13
N
O
10
11
Figure 2: e reported mechanistic pathways ꢀ and B [6] for the reaction of nitrous acid with oximes suggested the formation of sulfonyl-
diketone 7 during the reaction of nitrous acid with oxime 4. e proposed mechanistic pathway of the reaction of nitrous acid with ꢁ-keto
sulfones 3 through intermediate 1,2-oxazete 10, pathway C.
(5) 2-Benzofurancarboxylic Acid (12e). is acid was synthe-
sized 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 ꢂ 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,
acid (12d), and 2-benzofurancarboxylic acid (12e) were iso-
lated in 72%, 62%, 55%, 58%, and 62% yields, respectively,
by the reaction of ꢁ-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. e
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–
1H, H6), 13.80 (s, D O exchangeable, 1H, OH); 13C NMR ꢂ
2
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+].
1
e obtained commercially [16–20]. For example, H NMR
of acids 12a–e revealed the D O exchangeable signal of
2
3. Results and Discussion
carboxylic OH in the region ꢂ 13.0–13.8 whereas their 13C
NMR showed the signal due to the carbon of carbonyl
function in the region ꢂ 160.2–167.56. 1H NMR of 12a showed
the AB system of Para substituted benzene ring at ꢂ 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 ꢂ 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 reac-
tion of nitrous acid and nitrosonium ion NO+ with oximes
by Kliegman and Barnes [6]. ey proposed two mechanistic
pathways using 15N nitrous acid to determine the reaction
products. e 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).
ꢁ-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 ꢁ-keto sulfones 3a–e with sodium nitrite, in
acetic acid containing sulfuric acid, afforded the correspond-
ing 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 appli-
cation 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), [1,1ꢀ-biphenyl]-4-carboxylic
acid (12b), 2-naphthoic acid (12c), 2-thiophenecarboxylic
e nitrosating agent nitrous acid is formed in situ by
the action of acetic or mineral acid on sodium nitrite and

4
Journal of Chemistry
a further reaction takes place to give the nitrosonium ion
NO+ (Figure 2). e 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 pro-
duction of 1-aryl-2-(phenyl/tolylsulfonyl)ethane-1,2-dione 7
instead of arenecarboxylic acids 12 (Figure 2).
ese 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 inter-
mediate 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).
[7] H. A. Abdel-Aziz, K. A. Al-Rashood, K. E. H. Eltahir, and G.
M. Suddek, “Synthesis of N-benzenesulfonamide-1H-pyrazoles
bearing arylsulfonyl moiety: novel celecoxib analogs as potent
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[8] H. A. Abdel-Aziz, H. A. Ghabbour, M. A. Bhat, and H.-K. Fun,
“Microwave-assisted synthesis and characterization of certain
oximes, hydrazones and olefins derived from ꢀ-keto sulfones,”
Journal of Chemistry, vol. 2014, Article ID 532467, 6 pages, 2014.
[9] H. A. Abdel-Aziz, “Method for the preparation of carboxylic
acids,” European Patent, patent application pending no. EP
14163967.7, 2014.
[10] X. Wan, Q. Meng, H. Zhang, Y. Sun, W. Fan, and Z. Zhang, “An
efficient synthesis of chiral ꢀ-hydroxy sulfones via Ru-catalyzed
enantioselective hydrogenation in the presence of iodine,”
Organic Letters, vol. 9, no. 26, pp. 5613–5616, 2007.
[11] N. Samakkanad, P. Katrun, T. Techajaroonjit et al., “IBX/I2-
Mediated reaction of sodium arenesulfinates with alkenes: facile
synthesis of ꢀ-keto sulfones,” Synthesis, vol. 44, no. 11, pp. 1693–
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[12] D. Ruhlmann and J. P. Fouassier, “Relations structure-proprietes
dans les photoamorceurs de polymerisation-8. les derives de
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1079–1088, 1993.
4. 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.
[13] K. Kim, S. R. Mani, and H. J. Shine, “Ion radicals. XXXV. Reac-
tions of thianthrene and phenoxathiin cation radicals with
ketones. Formation and reactions of ꢀ-ketosulfonium perchlo-
rates and ylides,” Journal of Organic Chemistry, vol. 40, no. 26,
pp. 3857–3862, 1975.
Conflict of Interests
[14] Y. Din, A. Fan, and Z. Zhang, “Synthesis of 2-(arylsulfonyl)-1-(2-
thienyl)ethanones,” Yingyong Huaxue, vol. 14, no. 3, pp. 113–114,
1997.
e author has declared that there is no conflict of interests.
Acknowledgment
[15] H. A. Abdel-Aziz, S. W. Ng, and E. R. T. Tiekink, “1-(1-Benzo-
furan-2-yl)-2-(phenylsulfonyl) ethanone,” Acta Crystallograph-
ica, vol. E67, no. 10, Article ID o2675, 2011.
[16] https://www.sigmaaldrich.com/catalog/product/aldrich/135585.
[17] https://www.sigmaaldrich.com/catalog/product/aldrich/b34729.
[18] https://www.sigmaaldrich.com/catalog/product/aldrich/180246.
[19] https://www.sigmaaldrich.com/catalog/product/aldrich/t32603.
[20] https://www.sigmaaldrich.com/catalog/product/aldrich/307270.
e 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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