Rucl33h2o catalyzed tandem reaction of alkynylbromides with 2-aminothiophenols in water: A convenient synthesis of 2-benzoylbenzothiazoles

Article abstract of DOI:10.1071/CH11217

RuCl33H2O catalyzed tandem reaction of alkynyl bromides with 2-aminothiophenols mediated by water is shown to represent a convenient synthesis of 2-benzoylbenzothiazoles. In addition, the Ru(iii) catalyst could be readily recovered and efficiently reused together with water up to three times. CSIRO 2011.

Full text of DOI:10.1071/CH11217

CSIRO PUBLISHING
Aust. J. Chem. 2011, 64, 1568–1573
Full Paper
http://dx.doi.org/10.1071/CH11217
.
RuCl3 3H2O Catalyzed Tandem Reaction
of Alkynylbromides with 2-Aminothiophenols in Water:
A Convenient Synthesis of 2-Benzoylbenzothiazoles
A B
,
A
A
A B
,
Xuesen Fan,
Yan He, Shenghai Guo, and Xinying Zhang
A
School of Chemistry and Environmental Science, Key Laboratory of Green Chemical
Media and Reactions, Ministry of Education, Henan Key Laboratory for Environmental
Pollution Control, Henan Normal University, Xinxiang, Henan 453007, P. R. China.
Corresponding authors. Email: xuesen.fan@henannu.edu.cn; xinyingzhang@htu.cn
B
RuCl3ꢀ3H2O catalyzed tandem reaction of alkynyl bromides with 2-aminothiophenols mediated by water is shown to
represent a convenient synthesis of 2-benzoylbenzothiazoles. In addition, the Ru(III) catalyst could be readily recovered
and efficiently reused together with water up to three times.
Manuscript received: 28 May 2011.
Manuscript accepted: 19 July 2011.
Published online: 17 October 2011.
compounds, such as alkynylselenides,[17] alkynylsulfona-
mides,[18] heterocycles,[19–20] ynamides,[21] and enynes,[22] etc.
Herein, we report our preliminary results in this regard.
Introduction
Heteroaryl ketones are valuable synthetic synthons and frequent
structural units of many therapeutic agents.[1–5] To date, various
methods, such as Friedel–Crafts acylation of heteroaromatic
rings,[6] condensation of metalated heterocycles with nitriles,[7]
oxidation of 1-heteroaromatic-1-alkanols,[8–9] reaction of acyl
chlorides with organometallic reagents,[10] Pd-catalyzed car-
bonylative coupling of aryl halides with organometallic
reagents,[11] and Pd-catalyzed carbonylation of heteroarenes,[12]
have been developed for the synthesis of heteroaryl ketones.
While these methods are generally efficient and reliable, some
of them still suffer from the need to use expensive catalysts or
specially made starting materials. In addition, the use of highly
reactive organometallic precursors usually precludes the pres-
ence of labile functional groups on the substrates and so mild
reaction conditions are usually required. Further, the solvents
used are often volatile and relatively toxic and not well suited to
industrial settings. As a result, there would be widespread in-
terest in developing more practical and sustainable methods to
produce heteroaryl ketones.
Asa sustainable solvent, water isconsideredasone ofthe most
desirable since it is abundant, inexpensive and safe. To develop
synthetic procedures mediated by water is therefore a common
and important aim of green and sustainable chemistry.[13,14]
Based on the above observations and as a continuation of our
interests in developing new synthetic strategies for the prepara-
tion of heterocyclic compounds by using water as the reaction
medium[15] or by using RuCl3ꢀ3H2O as an efficient and selective
oxidative catalyst,[16] we envisioned a new route towards
heteroaryl ketones, specifically here benzoylbenzothiazoles,
via water mediated, RuCl3ꢀ3H2O promoted coupling of alkynyl
bromides with 2-aminothiophenols and benzylic oxidation of
the in situ formed 2-benzylbenzothiazole. Alkynyl bromides
attracted our attention because they are highly versatile synthetic
building blocks and have been used in the synthesis of a
plethora of biologically and synthetically interesting
Results and Discussion
To check the feasibility of our envisioned route, several
experiments were carried out by using 1-(2-bromoethynyl)
benzene (1a) and 2-aminothiophenol (2a) as model substrates
(Scheme 1).
Initially, 1a and 2a were treated with 0.05 equiv of
RuCl3ꢀ3H2O in water. It turned out that 3a could be obtained
in 55 % yield after the mixture of 1a and 2a was stirred at 408C
for 15 h (Table 1, entry 1). Higher reaction temperatures resulted
in shorter reaction times and higher yields (entries 2–4). It was
also observed that increasing the amount of RuCl3ꢀ3H2O to 0.1
equiv improved the yield of 3a to 81 % (entry 5). On the other
hand, in the absence of either RuCl3ꢀ3H2O or air, only trace
amount of 3a were formed according to TLC analysis, indicating
that both RuCl3ꢀ3H2O (cat.) and air are indispensable for the
formation of 3a (entries 7 and 8). It is worth noting that with a
catalytic amount of RuCl3ꢀ3H2O, air is actually acting as a
stoichiometric oxidant for this tandem reaction.
In order to compare the applicability of water with that of
routinely used organic solvents as medium for this tandem
process, the reaction of 1a and 2a was tried in THF, CH2Cl2,
or CH3CN. It followed that these organic solvents afforded 3a in
lower yields even though the reaction systems were completely
homogeneous (Table 1, entries 9–11). This does not necessarily
prove that water is the best solvent, as longer reaction times for
these lower boiling organic solvents may lead to an increased
yield. However, the aqueous conditions that we have discovered
to be effective are far more preferable from the perspective of
green chemistry.
With the optimized reaction conditions, the scope and
limitations of this reaction were explored. The results included
Journal compilation Ó CSIRO 2011
www.publish.csiro.au/journals/ajc

Synthesis of 2-Benzoylbenzothiazoles in Water
1569
in Table 2 show that aryl substituted alkynyl bromides with
either electron-withdrawing or electron-donating groups on the
aryl ring underwent this tandem process efficiently (entries 1–16).
On the other hand, benzyl substituted alkynyl bromides gave
2-phenethyl benzothiazoles without benzylic oxidation (entries
17–18), indicating that under these mild conditions the benzylic
oxidation was highly chemoselective and only occurred with
methylene groups immediately between two aromatic moieties.
As for the 2-aminothiophenol substrates, reactions with
3-chloro-2-aminothiophenol (entries 10–13) were less effective
than those with 2-aminothiophenol, 4-chloro- or 5-methyl-2-
aminothio phenol, probably due to steric hindrance. In addition,
it was observed that various functional groups, such as methyl,
methoxy, nitro, and halides, were compatible with the reaction
conditions.
O
NH2
SH
N
RuCl3·3H2O
solvent
ϩ
Br
S
1a
2a
3a
This is the first report of benzothiazol-2-yl ketones
prepared from tandem reactions of alkynyl bromides with
o-aminothiophenols by using water as the reaction medium.
Recently, we have reported that 2-benzoyl benzothiazoles could
be obtained from the condensation of o-aminothiophenol and
phenyl acetaldehyde under the promotion of FeCl3ꢀ6H2O in
[bmim]BF4,[23] or of 1,1-dibromoethenes with 2-amino(thio)
phenols promoted by TBAFꢀ3H2O and RuCl3 by using DMF as
the reaction medium.[24] To our knowledge, phenyl acetalde-
hyde derivatives are usually obtained through the Darzens
condensation between benzaldehydes and a-halo esters to give
a,b-epoxy esters and subsequent saponification of a,b-epoxy
esters followed by decarboxylation. This sequence of reactions
is hard to deal with and the yields of phenyl acetaldehydes are
low. Alkynyl bromides used in this protocol, on the other hand,
can be efficiently prepared from the condensation of aldehydes
with tetra-bromomethane followed by base promoted dehydro-
bromination.[25] In addition to readily available starting mate-
rials, the synthetic strategy developed in this paper features
another advantage over our previously reported protocols in that
Scheme 1.
Table 1. Optimization study for the synthesis of 3aA
Entry Solvent RuCl3ꢀ3H2O [equiv] Temp. [8C] Time [h] 3a [%]B
1
H2O
0.05
0.05
0.05
0.05
0.1
0.2
–
40
15
9
6
6
6
6
6
6
6
6
6
55
2
H2O
60
67
3
H2O
80
75
4
H2O
100
80
73
5
H2O
H2O
81
6
80
81
7
H2O
80
Trace
TraceC
71
8
H2O
0.1
0.1
0.1
0.1
80
9
THF
CH2Cl2
CH3CN
Reflux
Reflux
Reflux
10
11
72
64
A1a and 2a (1 mmol), H2O (5 mL), other solvents (10 mL).
BIsolated yields.
CUnder N2.
Table 2. Preparation of various benzothiazol-2-yl ketonesA
Entry
1
2
3
Yield [%]B
O
Br
NH2
SH
N
1
81
S
3a
O
Br
NH2
SH
N
2
3
4
80
78
82
S
H3C
H3CO
F
H3
C
3b
O
Br
NH2
SH
N
S
H3CO
3c
O
Br
NH2
SH
N
S
F
3d
O
O
Br
NH2
SH
N
N
5
6
86
S
S
O2N
H3C
O2
N
3e
3f
Br
NH2
SH
H3
C
75
(Continued)

1570
X. Fan et al.
Table 2. (Continued)
2
Entry
1
3
Yield [%]B
O
Br
NH2
SH
Cl
N
7
81
S
O
Cl 3g
Cl 3h
Cl 3i
3j
Br
NH2
SH
Cl
Cl
N
8
73
80
65
66
S
H3
C
H3
C
O
Br
NH2
SH
N
9
S
F
F
O
Cl
Br
N
Cl
NH2
10
11
S
SH
O
Cl
Br
N
Cl
NH2
S
H3
C
H3
C
SH
3k
O
Cl
Br
N
Cl
NH2
12
13
62
60
S
F
F
SH
3l
O
Cl
Br
H3C
N
Cl
NH2
H3
C
S
SH
3m
O
Br
N
NH2
SH
S
14
15
16
79
77
80
H3
C
H3C
H3C
H3C
H3
C
CH3
3n
O
Br
N
NH2
SH
S
N
H3CO
H3CO
CH3
3o
O
Br
NH2
SH
S
F
F
CH3
3p
4b
NH2
SH
S
Br
CH2CH2Ph
Ph
Ph
17
18
73
76
N
4a
NH2
SH
S
N
Cl
Br
CH2CH2Ph
Cl
A1 and 2 (1 mmol), RuCl3ꢀ3H2O (0.1 mmol), H2O (5 mL), 808C, 6 h.
BIsolated yields.
water is used as an environmentally sustainable and efficiency-
enhancing reaction medium.
in situ formed Ru(II) could be oxidized back to Ru(III) by air to
complete the catalytic cycle.
Based on the above observations, a plausible pathway for the
formation of 3a is depicted in Scheme 2. First, condensation of
1a and 2a affords an alkynylthiophenyl amine (A) or alkynyla-
minothiophenol (B), followed by intramolecular cyclization to
give 2-benzylbenzothiazole (C9). Ru(III)/air promoted oxidation
of the benzylic methylene moiety of C9 affords 2-benzothiazyl
ketone (3a) to conclude the tandem process. Meanwhile, the
Finally, the recovery and reuse of RuCl3 together with water
was studied by using 1a and 2a as model substrates. Upon
completion of the reaction, the resulting mixture was extracted
with diethyl ether (10 mL ꢁ 3) to remove the product and the
remaining aqueous phase was ready for reuse. The recovered
Ru(III)/H2O was reused three times and gave 3a in yields of 80,
78, and 70 %, respectively, for each reuse.

Synthesis of 2-Benzoylbenzothiazoles in Water
1571
NH2
2a
NH2
S
SH
SH
Ph
Br
or
Ph
H2O
N
H
Ph
1a
A
air
B
Ru(II)
Ru(III)
O
H
N
N
N
Ph
Ph
Ph
S
S
S
C
3a
C؅
Scheme 2.
In summary, an efficient and environmentally sustainable
preparation of 2-benzoylbenzothiazoles was developed. To our
knowledge, this is the first report in which heteroaryl ketones
have been synthesized from alkynyl bromides through a Ru(III)/
air promoted tandem process mediated by water. In addition, the
Ru(III) catalyst could be readily recovered and efficiently reused
together with water up to 3 times. Current studies are in progress
to extend the synthetic potential of this novel procedure.
(m, 2H), 8.02 (d, J ¼ 8.0 Hz, 1H), 8.24 (d, J ¼ 8.0 Hz, 1H), 8.65
(d, J ¼ 8.8 Hz, 2H). 13C NMR (100 MHz, CDCl3) d: 55.6, 113.9,
122.1, 125.5, 126.8, 127.4, 127.7, 133.8, 136.8, 153.9, 164.4,
167.9, 183.5. MS: m/z 270 (MH)þ.
2-(4-Fluorobenzoyl)benzothiazole (3d)[27]
Colourless solid, mp 116–1188C; 1H NMR (400 MHz,
CDCl3) d: 7.22–7.26 (m, 2H), 7.56–7.61 (m, 2H), 8.02–8.04
(m, 1H), 8.24 (d, J ¼ 7.2 Hz, 1H), 8.65–8.69 (m, 2H). 13C NMR
(100 MHz, CDCl3) d: 115.6, 115.9, 122.2, 125.7, 127.0, 127.7,
131.2, 134.1, 134.2, 136.9, 153.8, 167.0, 183.6. MS: m/z
258 (MH)þ.
Experimental Section
Thin-layer chromatography (TLC) was carried out with silica
gel 60 F254 pre-coated plates. Visualization was accomplished
with a UV lamp. NMR spectra were recorded using TMS as
internal standard and peak multiplicities are designated as fol-
lows: s, singlet; d, doublet; t, triplet; m, multiplet; dd, doublet of
doublets; td, triplet of doublets. Chemical shifts (d) were
expressed in ppm downfield from the internal standard tetra-
methylsilane and coupling constants J were given in Hz.
2-(4-Nitrobenzoyl)benzothiazole (3e)[27]
Yellow solid, mp 177–1788C; 1H NMR (400 MHz, CDCl3)
d: 7.59–7.63 (m, 2H), 8.04–8.06 (m, 1H), 8.25–8.28 (m, 1H),
8.40 (d, J ¼ 8.8 Hz, 2H), 8.74 (d, J ¼ 8.8 Hz, 2H). 13C NMR
(100 MHz, CDCl3) d: 122.3, 123.5, 124.3, 125.9, 127.3, 128.3,
132.3, 137.2, 139.7, 153.8, 165.8, 183.9. MS: m/z 285 (MH)þ.
Typical Procedure for the Preparation of 3a
2-(3-Methylbenzoyl)benzothiazole (3f)[23]
A mixture containing 1-(2-bromoethynyl)benzene (1a, 1 mmol),
2-aminothiophenol (2a, 1 mmol) and RuCl3ꢀ3H2O (0.1mmol) in
water (5mL) was stirred at 808C for 6 h. Upon completion, the
mixture was extracted with diethyl ether (5mLꢁ 3). The com-
bined organic phases were concentrated under vacuum. The
crude product was purified by column chromatography eluting
with ethyl acetate/hexane (3–5 %) to give 3a in a yield of 81%.
3b-3q were obtained in a similar manner.
Syrup; 1H NMR (400 MHz, CDCl3) d: 2.48 (s, 3H),
7.44–7.50 (m, 2H), 7.54–7.62 (m, 2H), 8.03 (d, J ¼ 8.0 Hz,
1H), 8.25–8.28 (m, 2H), 8.38 (d, J ¼ 7.6 Hz, 1H). 13C NMR
(100 MHz, CDCl3) d: 21.5, 122.2, 125.7, 126.9, 127.6, 128.4,
128.6, 131.4, 134.8, 134.9, 137.0, 138.3, 153.8, 167.2, 185.7.
MS: m/z 254 (MH)þ.
2-Benzoyl-5-chlorobenzothiazole (3 g)[23]
1
Colourless crystals, mp 133–1368C; H NMR (400 MHz,
2-Benzoylbenzothiazole (3a)[26]
Pale yellow solid, mp 97–988C; 1H NMR (400 MHz, CDCl3)
d: 7.55–7.63 (m, 4H), 7.69 (t, J ¼ 7.2 Hz, 1H), 8.04 (d, J ¼ 7.2 Hz,
1H), 8.27 (d, J ¼ 7.2 Hz, 1H), 8.58 (d, J ¼ 7.2 Hz, 2H). 13C NMR
(100 MHz, CDCl3) d: 122.2, 125.7, 126.9, 127.6, 128.5, 131.3,
133.9, 134.9, 137.0, 153.9, 167.1, 185.4. MS: m/z 240 (MH)þ.
CDCl3) d: 7.52–7.59 (m, 3H), 7.69 (t, J ¼ 7.6 Hz, 1H), 7.95
(d, J ¼ 7.6 Hz, 1H), 8.24 (d, J ¼ 2.0 Hz, 1H), 8.55 (d, J ¼ 7.6 Hz,
2H). 13C NMR (100 MHz, CDCl3) d: 123.0, 125.2, 128.2, 128.6,
131.3, 133.0, 134.1, 134.6, 135.2, 154.6, 168.9, 185.0. MS: m/z
274 (MH)þ.
2-(4-Methylbenzoyl)benzothiazole (3b)[26]
5-Chloro-2-(4-methylbenzoyl)benzothiazole (3h)[23]
Colourless crystals, mp 94–968C; 1H NMR (400 MHz,
CDCl3) d: 2.47 (s, 3H, CH3), 7.36 (d, J ¼ 8.0 Hz, 2H), 7.53–
7.58 (m, 2H), 7.99 (t, J ¼ 8.4 Hz, 1H), 8.24 (d, J ¼ 8.0 Hz, 1H),
8.48 (d, J ¼ 8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3) d: 21.9,
122.2, 125.7, 126.9, 127.4, 127.5, 129.3, 129.7, 131.4, 132.3,
136.9, 145.0, 153.9, 167.4, 184.9. MS: m/z 254 (MH)þ.
Yellow solid, mp 115–1178C; 1H NMR (400 MHz, CDCl3)
d: 2.47 (s, 3H), 7.36 (d, J ¼ 8.4 Hz, 2H), 7.51 (dd, J1 ¼ 8.4 Hz,
J2 ¼ 1.6 Hz, 1H), 7.93 (d, J ¼ 8.4 Hz, 1H), 8.22 (d, J ¼ 1.6 Hz,
1H), 8.46 (d, J ¼ 8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d: 21.9, 122.9, 125.1, 128.1, 129.3, 131.4, 132.0, 132.9, 135.1,
145.3, 154.6, 169.2, 184.4. MS: m/z 288 (MH)þ.
2-(4-Methoxylbenzoyl)benzothiazole (3c)[27]
5-Chloro-2-(4-fluorobenzoyl)benzothiazole (3i)[23]
Colourless solid, mp 120–1228C; 1H NMR (400 MHz,
Pink solid, mp 149–1518C; 1H NMR (400 MHz, CDCl3)
CDCl3) d: 3.93 (s, 3H), 7.05 (d, J ¼ 8.8 Hz, 2H), 7.52–7.61
d: 7.23–7.26 (m, 2H), 7.53 (dd, J1 ¼ 8.8 Hz, J2 ¼ 2.0 Hz, 1H),

1572
X. Fan et al.
7.94 (d, J ¼ 8.8 Hz, 1H), 8.23 (d, J ¼ 1.6 Hz, 1H), 8.64–8.68
(m, 2H). 13C NMR (100 MHz, CDCl3) d: 115.7, 115.9, 123.0,
125.2, 128.3, 130.9, 133.1, 134.2, 134.3, 135.2, 154.5, 165.2,
168.8, 183.1. MS: m/z 292 (MH)þ.
(m, 6H), 7.46 (t, J ¼ 8.0 Hz, 1H), 7.83 (d, J ¼ 8.0 Hz, 1H), 7.99
(d, J ¼ 8.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) d: 35.5, 36.0,
121.5, 122.6, 124.7, 125.9, 126.4, 128.4, 128.6, 135.1, 140.2,
153.1, 170.9. MS: m/z 240 (MH)þ.
2-Benzoyl-4-chlorobenzothiazole (3j)[23]
1
Pale yellow crystals, mp 111–1128C; H NMR (400 MHz,
5-Chloro-2-phenethylbenzothiazole (4b)
Pale brown solid, mp 93–958C; 1H NMR (400 MHz, CDCl3)
d: 3.20 (t, J ¼ 8.0 Hz, 2H), 3.42 (t, J ¼ 8.0 Hz, 2H), 7.21–7.34
(m, 6H), 7.73 (d, J ¼ 8.4 Hz, 1H), 7.96 (d, J ¼ 1.6 Hz, 1H); 13C
NMR (100 MHz, CDCl3) d: 35.4, 36.0, 122.2, 122.5, 125.2,
126.5, 128.4, 128.6, 132.0, 133.4, 139.9, 154.1, 172.9. MS: m/z
274 (MH)þ. HRMS (FAB) calcd for C15H13ClNS: 274.0458
[MþH], found: 274.0451.
CDCl3) d: 7.48 (t, J ¼ 8.0 Hz, 1H), 7.57–7.71 (m, 4H), 7.92
(d, J ¼ 8.0 Hz, 1H), 8.68 (d, J ¼ 8.0 Hz, 2H). 13C NMR
(100 MHz, CDCl3) d: 120.6, 127.0, 128.0, 128.5, 130.6, 131.5,
134.1, 134.6, 138.4, 151.0, 167.8, 184.5. MS: m/z 274 (MH)þ.
4-Chloro-2-(4-methylbenzoyl)benzothiazole (3k)[23]
Colourless solid, mp 119–1218C; 1H NMR (400 MHz,
CDCl3) d: 2.48 (s, 3H), 7.38 (d, J ¼ 8.0 Hz, 2H), 7.47 (t,
J ¼ 8.0 Hz, 1H), 7.61 (d, J ¼ 8.0 Hz, 1H), 7.91 (d, J ¼ 8.0 Hz,
1H), 8.59 (d, J ¼ 8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3) d:
21.9, 120.6, 127.0, 127.9, 129.4, 130.5, 131.7, 132.0, 138.4,
145.3, 151.1, 167.5, 184.1. MS: m/z 288 (MH)þ.
Acknowledgements
This work was financially supported by the National Natural Science
Foundation of China (20972042 and 20911140238), Innovation Scientists
and Technicians Troop Construction Projects of Henan Province (No.
104100510019) and PCSIRT (IRT1061).
4-Chloro-2-(4-fluorobenzoyl)benzothiazole (3l)[23]
References
Colourlesssolid, mp121–1238C;1H NMR (400 MHz, CDCl3)
d: 7.23–7.28 (m, 2H), 7.49 (t, J ¼ 8.0 Hz, 1H), 7.63 (d, J ¼ 7.6 Hz,
1H), 7.91 (d, J ¼ 8.0 Hz, 1H), 8.76–8.80 (m, 2H). 13C NMR
(100MHz, CDCl3) d: 115.8, 116.0, 120.7, 127.1, 128.2, 130.6,
134.4, 134.5, 138.4, 150.9, 167.6, 182.8. MS: m/z 292 (MH)þ.
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6-Methyl-2-(4-methylbenzoyl)benzothiazole (3n)[23]
Paleyellow solid, mp 105–1078C; 1H NMR (400 MHz, CDCl3)
d: 2.47 (s, 3H), 2.54 (s, 3H), 7.34–7.40 (m, 3H), 7.80 (s, 1H), 8.11
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CDCl3) d: 21.8, 121.7, 125.1, 128.7, 129.2, 131.3, 132.5, 137.2,
138.1, 144.8, 152.1, 166.4, 185.0. MS: m/z 268 (MH)þ.
2-(4-Methoxybenzoyl)-6-methylbenzothiazole (3o)[23]
Colourless solid, mp 137–1398C; 1H NMR (400 MHz,
CDCl3) d: 2.54 (s, 3H), 3.92 (s, 3H), 7.04 (d, J ¼ 8.8 Hz, 2H),
7.39 (d, J ¼ 8.4 Hz, 1H), 7.79 (s, 1H), 8.10 (d, J ¼ 8.4 Hz, 1H),
8.63 (d, J ¼ 8.8 Hz, 2H). 13C NMR (100 MHz, CDCl3) d: 21.8,
55.5, 113.8, 121.7, 125.0, 127.9, 128.6, 133.8, 137.2, 138.0,
152.1, 164.2, 166.8, 183.5. MS: m/z 284 (MH)þ.
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Colourless solid, mp 50–528C; 1H NMR (400 MHz, CDCl3)
d: 3.22 (t, J ¼ 8.0 Hz, 2H), 3.44 (t, J ¼ 8.0 Hz, 2H), 7.21–7.38

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