One-pot access to sulfonylated naphthalenediols/hydroquinones from naphthols/phenols with sodium sulfinates in an aqueous medium

Article abstract of DOI:10.1039/d0nj05285j

A one-pot method towards sulfonylated hydroquinones/naphthalenediols in an aqueous medium has been developed with up to 97% yield. The whole reaction requiring no transition-metal catalysts could proceed smoothly with hypervalent iodine compounds as the oxidant. Both naphthols and phenols were viable with inexpensive and readily available sodium sulfinates as the sulfonylation reagents under an ambient atmosphere. This procedure is scalable, and the products could be easily obtained without column chromatography isolation. This journal is

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One-pot access to sulfonylated naphthalenediols/
hydroquinones from naphthols/phenols with
sodium sulfinates in an aqueous medium†
Cite this:DOI: 10.1039/d0nj05285j
Lingxin Meng,a Ruike Zhang,a Yuqiu Guan,a Tian Chen,a Zhiqiang Ding,a
a
Gongshu Wang,a Aikebaier Reheman,*b Zhangpei Chen *a and Jianshe Hu
A one-pot method towards sulfonylated hydroquinones/naphthalenediols in an aqueous medium has
been developed with up to 97% yield. The whole reaction requiring no transition-metal catalysts could
proceed smoothly with hypervalent iodine compounds as the oxidant. Both naphthols and phenols were
viable with inexpensive and readily available sodium sulfinates as the sulfonylation reagents under an
ambient atmosphere. This procedure is scalable, and the products could be easily obtained without
column chromatography isolation.
Received 28th October 2020,
Accepted 25th November 2020
DOI: 10.1039/d0nj05285j
rsc.li/njc
Consequently, the preponderance of sulfone-containing
hydroquinones has expedited the exploration of reliable meth-
Introduction
Naphthalenediol and hydroquinone derivatives are important struc- ods for their preparation.6 Some classical approaches include
tural motifs and omnipresent in many bioactive pharmaceuticals, oxidation of sulfides and electrophilic sulfonylation of arenes.7
agricultural drugs, dyestuffs, antioxidants, and materials.1 Among However, the limited substrate scope and tedious synthesis of
them, the sulfone-containing hydroquinones have been found to the starting materials impeded their further applications. Sub-
possess potential pharmacological activities.2 As depicted in Fig. 1, sequently, the method of conjugate addition of arylsulfinic acids
sulfone-containing hydroquinones 2-tosylnaphthalene-1,4-diol A to benzoquinones in ionic liquid solvents was developed by
and 2-tosylbenzene-1,4-diol B are potent inhibitors of b-Ketoacyl- Yadav and co-workers (Scheme 1a).8 Similarly, the addition
ACP-synthase III (FabH), an essential condensing enzyme in bacter- reactions of arylsulfinic salts with benzoquinones were also
ial fatty acid bio-synthesis.3 The alkylsulfuryl diverged hydroquinone achieved by using trifluoroacetic acid (TFA) or NH4I as the
C is the inhibitor of coenzyme Q systems4 and the quinoline based promoter, respectively (Scheme 1b).9,10 In 2017, the Wu group
sulfones D exhibited good activities as liver X receptor agonists.5
developed Cu and Mn synergistically facilitated sulfonylation of
quinones with aryl(alkyl)sulfonyl hydrazides as the sulphur
source (Scheme 1c).11 In the same year, Wei and co-workers
found that water and heat could also promote this transforma-
tion, providing the desired sulfonylated products with moderate
to excellent yields.12 Another approach was based on transition-
metal-catalyzed C–H sulfonylation of quinones with copper,
rhodium, palladium, and iridium as the catalyst and sulfonyl
chloride as the sulphur source, and then followed by reduction
(Scheme 1d).12 Although these reported procedures are generally
reliable, the development of more efficient and greener synthetic
approaches to versatile sulfone-containing hydroquinones still
remains highly desirable.
Fig. 1 Examples of bioactive sulfone-containing naphthalenediols and
hydroquinones.
Considering that the quinones are generally obtained by oxidation
of hydroquinones,13 directly converting hydroquinones into the corres-
ponding sulfonylated hydroquinones in one-step would provide an
efficient, step-economic and attractive protocol for these compounds.
Herein, we report our findings toward the construction of various
sulfonylated naphthalenediols and hydroquinones from naphthols or
phenols with sodium sulfinates in an aqueous medium (Scheme 1e).
a Center for Molecular Science and Engineering, College of Sciences,
Northeastern University, Shenyang 110819, P. R. China.
E-mail: chenzhangpei@mail.neu.edu.cn
b Key Laboratory of Toxicology, Medical College, Ningde Normal University, Ningde,
352100, China. E-mail: akbarphd@126.com
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
d0nj05285j
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Table 1 Condition optimization
Entrya Oxidant Solvent
Additive
Time (h) Yieldb (%)
1
2
3
4
5
6
PIDA
PIDA
PIDA
PIDA
PIDA
PIDA
PIDA
PIDA
H2O
—
—
—
—
1
1
1
1
1
1
1
1
1
1
1
1
1
5
3
3
3
3
3
28
50
22
37
76
70
68
66
20
80
N.R.
N.R.
N.R.
82
89
89
89
80
MeOH : H2O = 2 : 1
DCM : H2O = 2 : 1
DMSO : H2O = 2 : 1
CH3CN : H2O = 2 : 1 —
CH3CN : H2O = 1 : 1 —
CH3CN : H2O = 1 : 2 —
CH3CN : H2O = 2 : 1 —
7
8c
9
m-CPBA CH3CN : H2O = 2 : 1 —
PIFA
H2O2
10
11
12
13
14
15
16
17
18
19
20
21d
CH3CN : H2O = 2 : 1 —
CH3CN : H2O = 2 : 1 —
K2S2O8 CH3CN : H2O = 2 : 1 —
TBHP
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
CH3CN : H2O = 2 : 1 —
CH3CN : H2O = 2 : 1 —
CH3CN : H2O = 2 : 1 CH3COOH
CH3CN : H2O = 2 : 1 TFA
CH3CN : H2O = 2 : 1 TsOH
CH3CN : H2O = 2 : 1 Et3N
CH3CN : H2O = 2 : 1 NaHCO3
CH3CN : H2O = 2 : 1 HCl (aqua.) 3
CH3CN : H2O = 2 : 1 HCl (aqua.) 3
Scheme 1 Synthetic strategies for sulfonylated naphthalenediols or
hydroquinones.
74
91
85
a
Results and discussion
Reaction conditions: 1a (0.30 mmol), oxidant (0.66 mmol, 2.2 equiv.),
and solvent (3.0 mL) were added to a flask and stirred at room
temperature for 1 h under air; then the additive (0.30 mmol, 1.0 equiv.)
and 2a (0.36 mmol, 1.2 equiv.) were added, and the mixture was stirred
Our initial study began with the sulfonylation reaction between the
1-naphthalenol 1a and sodium 4-methylbenzenesulfinate 2a as
model substrates to optimize the reaction conditions (Table 1).
The easy available and widely used (diacetoxyiodo)benzene (PIDA)
was selected as the in situ oxidant to facilitate the one-pot reaction.
As shown in entry 1, when we mixed 1a and PIDA in water for 1 h
b
for another certain time to generate the product. Isolated yields after
c
column chromatography; N.R. means no reaction. 1a, 2a, solvent and
the oxidant were added together and the mixture was stirred for 4 h.
d
Reaction time of the oxidation process (step 1) was reduced to 0.5 h.
first, then added 1.2 equivalent of 2a to the mixture and stirred the providing 3a with 91% yield (entry 20). Notably, reducing the
reaction for another hour, the desirable product 3a was obtained oxidation process to 0.5 h, the yield decreased slightly, providing
with 28% isolated yield. Subsequently, we carefully studied the 3a in 85% yield (entry 21). Thus, the optimized reaction conditions
solvent effects on the yields, including the mixture solvents of were established as 1a (1.0 equiv.), PIFA (2.2 equiv.) and CH3CN/
methanol (MeOH), dichloromethane (DCM), dimethylsulfoxide H2O = 2 : 1 (3.0 mL), stirred for 1 h first and then aqueous HCl
(DMSO) and acetonitrile with water (entries 2–5). To our delight, (1.0 equiv.) and 2a (1.2 equiv.), stirred for another 3 h at room
with the employment of CH3CN/H2O (volume ratio 2:1) as the temperature.
reaction medium, the reaction could proceed smoothly, providing
After establishing the optimal conditions, we examined the
3a with 76% yield. However, further altering the volume ratio of substrate scope of this sulfonylation reaction and the results
acetonitrile and water failed to promote the yield (entries 6 and 7). are summarized in Scheme 2. Gratifyingly, a variety of sodium
It is worth mentioning that subjecting the substrates with PIDA in arylsulfinates were smoothly coupled to the 1-naphthalenol
one portion to the solvent and stirring the mixture for 4 h could scaffold, delivering the corresponding sulfonylated naphthalene-
also obtain the desired product with a slightly lower yield of 66% diols in 78–96% yields (3a–h). Various substituents on the
(entry 8). Then, we investigated the effect of other oxidants on the phenyl group of sodium arylsulfinate are tolerated in this
yield of this sulfonylation, including 3-chloroperoxybenzoic acid reaction, including tertiary butyl, trifluoromethyl, and halogen.
(m-CPBA), [bis(trifluoroacetoxy)iodo]benzene (PIFA), H2O2, K2S2O8 The electronic properties of the substituted groups in the
and tert-butyl hydroperoxide (TBHP), and the PIFA showed the best phenyl group of sodium arylsulfinates had little effect on the
result of 80% yield (entries 9–13). Disappointingly, prolongation of reactivity and a phenyl group bearing an ortho-fluorine atom
the reaction time failed to increase the yield, and this may be was also tolerated giving 94% isolated yield (3h). It was noted
attributed to the favouring of side reactions according to the that the sulfonylation reaction with alkyl substituted sodium
previous results (entry 14).14 Documents have demonstrated that sulfinates also occurred with high yields (3i–j). Significantly,
acids or bases could promote sulfonylation reactions;9,15 therefore, the sulfonylation of various phenols was also viable (3k–r). For
we turned our attention to evaluating the effects of various phenols, the scope of sodium arylsulfinates, including phenyl
additives (entries 15–20). After a systematic screening, the com- groups bearing various electron-donating groups or electron-
monly used hydrochloric acid was proven as the best choice, withdrawing substituents, proved to be broad, and all of the
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Scheme 3 Sulfonylation reactions with hydroquinone 4a,b
.
aPIDA
(0.33 mmol), hydroquinone 4 (0.30 mmol), H2O (3.0 mL), aqueous HCl
(0.30 mmol) and sodium sulfinate 2 (0.36 mmol) were added to a flask and
b
stirred at room temperature for 5 min under air. Isolated yields.
Scheme 2 Substrate scope of one-pot sulfonylation reactionsa,b. aReaction
conditions: phenols 1 (0.30 mmol), PIFA (0.66 mmol), CH3CN : H2O = 2 : 1
(3.0 mL), r.t., air, 1 h, and then aqueous HCl (0.30 mmol), sodium sulfinate 2
b
(0.36 mmol), r.t., air, 3 h. Isolated yields after column chromatography.
c
Scheme 4 Sulfonylation of 4-methoxyphenol in water.
4.0 equiv. of sodium 4-methylbenzenesulfinate 2a, 80 1C.
Interestingly, on exposure of 4-methoxyphenol 5 to the mixture
of PIDA, sulfonylnation reagent and aqueous HCl, the product 3l
was achieved in 61% yield (Scheme 4). According to the litera-
ture,16 this result may be ascribed to the effect of solvent. Water
was supposed to be involved in the oxidization process, the
excessive amount of H2O promoted the formation of p-quinone
and was then followed by sulfonylation with sodium sulfinates to
afford the product 3l.
corresponding products were isolated in 68–77% yields.
Notably, the nitro group remained intact in this reaction,
leading to the sulfonylated product 3o with 74% yield. In
addition, the transformation with alkyl substituted sodium
sulfinate also worked well, affording the desired product
in 72% yield (3p). Moreover, dimethyl substituted phenol
2,5-dimethylphenol was also demonstrated as a suitable substrate,
affording the corresponding sulfonylated product 3q in 80%
yield; meanwhile, with a higher temperature and an excessive
amount of sulfonylation reagent, the 2,6-dimethylphenol could
also be transformed into the corresponding product 3r in
68% yield.
To further estimate the application possibility, the gram-
scale synthesis studies were carried out. As shown in Scheme 5,
both 1-naphthalenol 1a and hydroquinone 4 were transformed
To further simplify the sulfonylation procedure, the transfor-
mation of hydroquinone 4 with sodium sulfinates was conducted
in one step. By introducing PIDA as the oxidant and water as the
solvent, the whole reaction proceeded immediately after charging
all reagents in one flask together (conditions optimization see
ESI†). As shown in Scheme 3, a variety of aryl and alkyl substituted
sodium sulfinates were smoothly coupled with the hydroquinone
and furnished the corresponding products in good to excellent
yields (70–97%). It was noted that the best result of 97% yield
was achieved when sodium 4-methylbenzenesulfinate 2a was
employed as the sulfonylation reagent.
Scheme 5 Gram-scale synthesis.
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3 M. M. Alhamadsheh, N. C. Waters, S. Sachdeva, P. Lee and
K. A. Reynolds, Bioorg. Med. Chem. Lett., 2008, 18,
6402–6405.
into the corresponding products successfully with excellent
yields under the optimized conditions, respectively. Signifi-
cantly, the products could be easily isolated through a simple
work-up process of filtration, washing with water and hexane.
´
4 J. Vorkapic-Furac, T. Kishi, H. Kishi, T. H. Porter and
K. Folkers, Acta Pharm. Suec., 1977, 14, 197–204.
5 R. C. Bernotas, R. R. Singhaus, D. H. Kaufman, J. M. Travins,
J. W. Ullrich, R. Unwalla, E. Quinet, M. Evans, P. Nambi,
A. Olland, B. Kauppi, A. Wilhelmsson, A. Goos-Nilsson and
J. Wrobel, Bioorg. Med. Chem. Lett., 2010, 20, 209–212.
6 (a) R. N. Warrener, D. A. C. Evans and R. A. Russell, Tetra-
hedron Lett., 1984, 25, 4833–4836; (b) D. E. Allgeier,
S. A. Herbert, R. Nee, K. D. Schlecht and K. T. Finley,
J. Org. Chem., 2003, 68, 4988–4990; (c) D. Habibi,
A. Rahimi, A. Rostami and S. Moradi, Tetrahedron Lett.,
2017, 58, 289–293; (d) S. Rouhani, A. Rostami, A. Salimi and
O. Pourshiani, Biochem. Eng. J., 2018, 133, 1–11;
(e) S. M. Maddox, G. A. Dawson, N. C. Rochester,
A. B. Ayonon, C. E. Moore, A. L. Rheingold and
J. L. Gustafson, ACS Catal., 2018, 8, 5443–5447.
Conclusions
To sum up, we have developed a one-pot method towards various
sulfonylated hydroquinones and naphthalenediols in an aqueous
medium with up to 97% yield. This metal-free transformation
occurred smoothly with hypervalent iodine compounds as the
oxidant. Both naphthols and phenols were viable with inexpensive
and readily available sodium sulfinates as the sulfonylation
reagents under an ambient atmosphere. This procedure is scal-
able, low-cost, experimentally simple, and the products could be
easily obtained without column chromatography isolation. Further
investigations of the synthesis and utility of these sulfonylated
compounds are underway in our lab.
´
7 (a) J. F. Bereznak and M. M. Joullie, Synth. Commun., 1989,
Conflicts of interest
19, 3573–3578; (b) M. V. R. Reddy, S. Vijayalakshmi,
D. B. Reddy and P. V. R. Reddy, Phosphorus, Sulfur Silicon
There are no conflicts to declare.
´
Relat. Elem., 1991, 60, 209–214; (c) Y. St-Denis, S. Levesque,
´
B. Bachand, J. J. Edmunds, L. Leblond, P. Preville, M. Tarazi,
P. D. Winocour and M. A. Siddiqui, Bioorg. Med. Chem. Lett.,
2002, 12, 1181–1184; (d) P. Lassalas, B. Gay, C. Lasfargeas,
M. J. James, V. Tran, K. G. Vijayendran, K. R. Brunden,
M. C. Kozlowski, C. J. Thomas, A. B. Smith, 3rd, D. M. Huryn
and C. Ballatore, J. Med. Chem., 2016, 59, 3183–3203.
8 J. Yadav, B. Reddy, T. Swamy and N. Ramireddy, Synthesis,
2004, 1849–1853.
Acknowledgements
Financial support from the National Natural Science Founda-
tion of China (21702026 and 21861040) and Fundamental
Research Funds for the Central Universities (N2005004 and
N180705004) is acknowledged.
9 J. M. Bruce and P. Lloyd-Williams, J. Chem. Soc., Perkin
Trans. 1, 1992, 2877–2884.
Notes and references
10 B. Li, Y. Li, L. Yu, X. Wu and W. Wei, Tetrahedron, 2017, 73,
2760–2765.
11 P.-G. Li, Y.-C. Li, T. Zhu, L.-H. Zou and Z. Wu, Eur. J. Org.
Chem., 2017, 6081–6084.
´
1 (a) E. Elhalem, B. N. Bailey, R. Docampo, I. Ujvary,
S. H. Szajnman and J. B. Rodriguez, J. Med. Chem., 2002,
45, 3984–3999; (b) J. Wang, J. N. Park, X. Y. Wei and
C.
W.
Lee,
Chem.
Commun.,
2003,
628–629;
12 (a) B. Ge, D. Wang, W. Dong, P. Ma, Y. Li and Y. Ding,
Tetrahedron Lett., 2014, 55, 5443–5446; (b) D. Wang, X. Yu,
B. Ge, H. Miao and Y. Ding, Chin. J. Org. Chem., 2015, 35,
676–680; (c) X. Yu, Q. Wu, H. Wan, Z. Xu, X. Xu and
D. Wang, RSC Adv., 2016, 6, 62298–62301; (d) L. Wang,
Y.-B. Xie, Q.-L. Yang, M.-G. Liu, K.-B. Zheng, Y.-L. Hu and
N.-Y. Huang, J. Iran. Chem. Soc., 2016, 13, 1797–1803.
13 (a) Y. Tamura, T. Yakura, J. Haruta and Y. Kita, J. Org. Chem.,
1987, 52, 3927–3930; (b) Y. Tamura, T. Yakura, H. Tohma,
K. Kikuchi and Y. Kita, Synthesis, 1989, 126; (c) Y. Kita,
T. Dohi, T. Nakae, N. Takenaga, T. Uchiyama, K.-I.
Fukushima and H. Fujioka, Synthesis, 2012, 1183–1189.
14 (a) Y. Kita, T. Yakura, H. Tohma, K. Kikuchi and Y. Tamura,
Tetrahedron Lett., 1989, 30, 1119–1120; (b) S. Sarkar,
M. K. Ghosh and M. Kalek, Tetrahedron Lett., 2020,
61, 152459.
(c) K. Miyashita and T. Imanishi, Chem. Rev., 2005, 105,
4515–4536; (d) D. Nematollahi, S. Momeni and
S. Khazalpour, Electrochim. Acta, 2014, 147, 310–318;
(e) J. Du, L. Ma, D. Shan, Y. Fan, L. Zhang, L. Wang and
X. Lu, J. Electroanal. Chem., 2014, 722–723, 38–45;
( f ) A. Kamimura, T. Nokubi, R. Watanabe, M. Ishikawa,
K. Nasu, H. Uno and M. Sumimoto, J. Org. Chem., 2014, 79,
1068–1083; (g) X. Li, Z. Zheng, H. Liu and Y. Gao, Electro-
phoresis, 2020, 41, 1991–1999.
2 (a) J. T. Tsay, W. Oh, T. J. Larson, S. Jackowski and
C. O. Rock, J. Biol. Chem., 1992, 267, 6807–6814;
(b) M. M. Alhamadsheh, N. C. Waters, D. P. Huddler,
M. Kreishman-Deitrick, G. Florova and K. A. Reynolds,
Bioorg. Med. Chem. Lett., 2007, 17, 879–883; (c) P. J. Lee,
J. B. Bhonsle, H. W. Gaona, D. P. Huddler, T. N. Heady,
M. Kreishman-Deitrick, A. Bhattacharjee, W. F. McCalmont,
L. Gerena, M. Lopez-Sanchez, N. E. Roncal, T. H. Hudson,
J. D. Johnson, S. T. Prigge and N. C. Waters, J. Med. Chem.,
2009, 52, 952–963.
15 (a) Y. Ogata, Y. Sawaki and M. Isono, Tetrahedron, 1969, 25,
2715–2721; (b) M. P. Lockshin, M. P. Filosa and M. J. Zuraw,
J. Org. Chem., 1996, 61, 2556–2558; (c) D. E. Allgeier,
New J. Chem.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2020

View Article Online
NJC
S. A. Herbert, R. N. Kenneth, D. Schlecht and K. T. Finley,
Paper
Hoboken, 2001, ch. 2, pp. 327–333; (c) A. Wu, Y. Duan, D. Xu,
T. M. Penning and R. G. Harvey, Tetrahedron, 2010, 66,
J. Org. Chem., 2003, 68, 4988–4990.
´
16 (a) R. Barret and M. Daudon, Tetrahedron Lett., 1990, 31,
4871–4872; (b) R. M. Moriarty and O. Prakash, in Organic
Reactions, ed. L. E. Overman, et al., John Wileys & Sons, Inc,
2111–2118; (d) L. Pouysegu, D. Deffieux and S. Quideau, Tetra-
hedron, 2010, 66, 2235–2261; (e) K. Signo, Z. Mammasse and
S. Canesi, J. Org. Chem., 2020, 85, 2832–2837.
New J. Chem.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2020