One-pot synthesis of benzo[1,4]thiazin-3(4 H)-ones and a theoretical study of the S-N type smiles rearrangement mechanism

Article abstract of DOI:10.1021/jo3014287

Benzo[1,4]thiazin-3(4H)-one derivatives are conveniently prepared in one pot via a Smiles rearrangement (SR) tandem reaction. In order to understand the reaction, we present here a theoretical study on the S-N type SR mechanism.

Full text of DOI:10.1021/jo3014287

Article
pubs.acs.org/joc
One-Pot Synthesis of Benzo[1,4]thiazin-3(4H)‑ones and a Theoretical
Study of the S−N Type Smiles Rearrangement Mechanism
Yongmei Zhao,† Yanmiao Wu,‡ Jiong Jia,† Dongju Zhang,*,† and Chen Ma*,†
†School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, People's Republic of China
‡College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250100, People's Republic
of China
S
* Supporting Information
ABSTRACT: Benzo[1,4]thiazin-3(4H)-one derivatives are conven-
iently prepared in one pot via a Smiles rearrangement (SR) tandem
reaction. In order to understand the reaction, we present here a
theoretical study on the S−N type SR mechanism.
Scheme 1. Ipso SR vs Direct Nucleophilic Substitution on
the Ortho Position
INTRODUCTION
■
A great number of biologically active molecules and natural
products contain the benzo[1,4]thiazin-3(4H)-one scaffold.1
For example, 2H-benzo[1,4]thiazin-3(4H)-one derivatives act
as bacteriostatic,2 antiarrhythmic,3 and antidiabetic agents.4 4H-
Benzo[1,4]thiazin-3(4H)-ones are used as herbicides.5 Because
of this, some methods for the synthesis of benzo[1,4]thiazin-
3(4H)-ones have been developed. Most commonly, a multistep
reaction,6 a copper-catalyzed reaction,7 and a Smiles rearrange-
ment (SR) reaction8 are taken into consideration. However,
there are still some disadvantages of the existing methods,
which are limited to synthesizing a substituent diversification of
products, such as N-aryl-substituted products. Moreover, the
yields of the substituted products are low because of the
multistep reaction. Additionally, the reaction conditions are a
bit rigorous. Therefore, a new and more effective method,
involving mild, environmentally benign, atom-economical, and
metal-free conditions, is still in high demand for synthesizing
2H-benzo[1,4]thiazin-3(4H)-ones.
In a continuation of our studies on the development of
economical syntheses of heterocyclic systems,9 we herein used
1 (4) and 2 (5) to synthesize a series of compounds 3 (Tables
2 and 3) via a Smiles rearrangement (SR)10 in a one-pot metal-
free reaction which is quite different from the reported
procedure.8 Furthermore, a mechanistic study of this S−N
type SR process is essential for designing the desired
benzo[1,4]thiazin-3(4H)-one derivatives and it is also
important for understanding the novel process. Therefore, we
performed a theoretical study to rationalize experimental
observations. To the best of our knowledge, the mechanism
of SR reactions, in particular the SR on the benzene ring, has
been rarely studied, although a few relevant theoretical studies
have been reported.11 In the present paper, we turn our
attention to a representative SR process with R = CH3, as
shown in Scheme 1. By performing quantum chemistry
calculations, we show the molecular mechanism for the S−N
type SR. To rationalize the experimental fact that the reaction is
substantially predominant via the SR, we also considered the
possibility of direct nucleophilic attack by the N atom on the
ortho position (path II in Scheme 1) and compared the results
with those of the ipso SR.
RESULTS AND DISCUSSION
■
To optimize the reaction conditions, we systematically
investigated the reaction parameters using 1a and 2 (Table
1). First, the effect of bases was investigated (entries 1−4). It
was found that the alkali-metal carbonate Cs2CO3 afforded 3a
in excellent yields, whereas other bases, such as K2CO3, DBU,
and NaOH, were less effective. Then we probed the influence
of different solvents on the reaction. DMF was found to be an
effective solvent for good results. CH3CN, DMSO, and THF
were found to be less effective.
With the optimized reaction conditions in hand, we then
explored the scope and generality of the synthesizing
benzo[1,4]thiazin-3(4H)-ones via Smiles rearrangement (Ta-
bles 2 and 3). The desired benzo[1,4]thiazin-3(4H)-ones were
Received: July 13, 2012
© XXXX American Chemical Society
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a
a
Table 1. Optimization of Conditions
Table 3. Synthesis of Benzo[1,4]thiazin-3(4H)-ones 5
b
entry
base
solvent
time (h)
yield (%)
1
2
3
4
5
6
7
Cs2CO3
NaOH
K2CO3
DBU
DMF
7
8
51
17
14
16
30
36
41
DMF
DMF
10
8
DMF
Cs2CO3
Cs2CO3
Cs2CO3
CH3CN
DMSO
THF
11
10
10
a
Reaction conditions: 1-chloro-2-nitro-4-(trifluoromethyl)benzene 1a
(0.5 mmol), N-benzyl-2-mercapto acetamide 2 (0.6 mmol), and base
(1.5 mmol) in solvent (15.0 mL) under N2 at room temperature.
b
Isolated yield.
a
Table 2. Synthesis of Benzo[1,4]thiazin-3(4H)-ones 3
a
Reaction conditions: 3,4-difluorobenzonitrile 1b (0.5 mmol), 2-
mercapto-N-methylacetamide 4a and analogues 4b−k (0.6 mmol),
and Cs2CO3 (1.5 mmol) in DMF (15.0 mL) under N2 at 80 °C for 4
a
b
Reaction conditions: 1-chloro-2-nitro-4-(trifluoromethyl)benzene 1a
h. Isolated yield.
and analogues 1b−d (0.5 mmol), N-benzyl-2-mercaptoacetamide 2
(0.6 mmol), and base Cs2CO3 (1.5 mmol) in DMF (15.0 mL) under
N2 at room temperature for 10 h. Isolated yield.
To rationalize the experimental observation that the SR
pathway (denoted as pathway I in Scheme 1) is substantially
predominant over the direct nucleophilic substitution pathway
(denoted as pathway II in Scheme 1), we have performed
theoretical calculations on the representative system (Scheme
1) in the framework of density functional theory (DFT),
employing the popular B3LYP functional12,13 with the standard
6-311+g(d,p) basis set,14 as implemented in the Gaussian 03
software package.15 This level of theory has been shown to
provide reliable accuracy to evaluate structures16 and
energetics17 and has been successfully applied to the study of
heterocyclic systems.18
b
obtained in 50% to 88% yields (Tables 2 and 3). As shown in
Table 2, substrate 1 with stronger electron-withdrawing groups
on the aromatic rings gave higher yields. The reaction
temperature was increased to 80 °C to shorten the reaction
time (Table 3). For the variation of R2, on comparison of the
yield of 5c with those of 5a,b, it was obvious that N-alkyl
substrates showed a small steric hindrance effect (Table 3,
entries 1−6). We also found that the N-aryl substrates with an
electron-donating group (Table 3, entries 7−9) provided
higher yields than the substrates with electron-withdrawing
groups (Table 3, entries 10 and 11). The molecular structure of
the representative product 5a was determined by X-ray
crystallography analysis (Figure 1).
Molecular geometries of minima and transition states were
completely optimized by total energy minimization with the use
of analytic gradient techniques. Harmonic vibrational frequency
calculations have also been conducted to verify all stationary
B
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Figure 1. X-ray structure of compound 5a with the atomic numbering scheme.
Figure 2. Optimized structures for transition states, intermediate, and products involved along pathways I and II. Distances are in Å.
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points as minima (zero imaginary frequency) or first-order
saddle points (one imaginary frequency). Intrinsic reaction
coordinates (IRC)19,20 were calculated for the transition states
to verify that such structures indeed connect two relevant
minima.
Figure 2 shows the optimized geometries of minimum and
transition states along both the two pathways, and Figure 3
favorable than the direct nucleophilic substitution pathway.
This transition-metal-free process has potential applications in
the synthesis of biologically and medicinally relevant com-
pounds.
EXPERIMENTAL SECTION
■
General Experimental Procedures for the Synthesis of
Benzo[1,4]thiazin-3(4H)-ones. A 25 mL Schlenk tube equipped
with a magnetic stirring bar was charged with 2-mercaptoacetamide
substrates (0.6 mmol, 1.2 equiv), aryl halides (0.5 mmol, 1.0 equiv),
and Cs2CO3 (489 mg, 1.5 mmol, 3.0 equiv), and then 15 mL of DMF
was added via syringe at room temperature and the mixture was
prestirred for about 15 min. Then the reaction mixture was stirred at
room temperature (3a−d) or 80 °C (5a−k). After the reaction was
complete, the mixture was diluted with brine (40 mL) and extracted
with ethyl acetate twice (2 × 30 mL). The combined organic layers
were dried with MgSO4, and the solvent was removed in vacuo to
afford a residue. The crude product was then purified by column
chromatography on silica gel to give the pure product.
4-Benzyl-7-(trifluoromethyl)-2H-benzo[1,4]thiazin-3(4H)-one
(3a): 165 mg (51% yield), yellow liquid; 1H NMR (CDCl3, 300 MHz)
δ 7.62 (d, J = 1.8 Hz, 1H), 7.39−7.27 (m, 4H), 7.19 (dd, J = 1.5, 8.1
Hz, 2H), 7.08 (d, J = 8.4 Hz, 1H), 5.26 (s, 2H), 3.56 (s, 2H); 13C
NMR (CDCl3, 75 MHz) δ 165.0, 142.2, 136.0, 129.0, 128.0, 127.9,
127.5, 126.2, 125.9, 125.4 (dd, J = 3.8 Hz, 1C), 124.5, 124.2, 124.2,
118.1, 48.4, 31.1; ESI-MS m/z 324.1 (M + H)+; FT-HRMS (ESI)
calcd for C16H12F3NOS (M + H)+ 323.0664, found 323.0668.
4-Benzyl-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-7-carbonitrile
Figure 3. Calculated relative energy profiles along the ipso SR pathway
(pathway I) and the direct nucleophilic substitution pathway (pathway
II).
1
(3b): 233 mg (83% yield), white solid; mp 110−112 °C; H NMR
(CDCl3, 300 MHz) δ 7.64 (d, J = 1.8 Hz, 1H), 7.31 (m, 4H), 7.16 (d,
J = 6.9 Hz, 2H) 7.06 (d, J = 8.7 Hz, 1H), 5.25 (s, 2H), 3.56 (s, 2H);
13C NMR (CDCl3, 75 MHz) δ 164.7, 142.9, 135.6, 131.7, 130.9, 129.0,
128.8, 127.9, 127.7, 126.2, 125.1, 118.4, 117.8, 107.1, 48.3, 30.8; ESI-
MS m/z 281.1 (M + H)+; FT-HRMS (ESI) calcd for C16H12N2OS (M
+ H)+ 281.0743, found 281.0740.
4-Benzyl-7-nitro-2H-benzo[b][1,4]thiazin-3(4H)-one (3c): 181 mg
(60% yield), brown solid; mp 37−39 °C; 1H NMR (CDCl3, 300
MHz) δ 8.25 (d, J = 1.8 Hz, 1H), 7.95 (dd, J = 2.7 Hz, 9.3, 1H), 8.25
(d, J = 2.7 Hz, 1H), 7.95 (dd, J = 2.7, 9.3 Hz, 1H), 7.31 (m, 3H), 7.20
(dd, J = 13.5, 15.0 Hz, 2H), 7.10 (d, J = 9.0 Hz, 1H), 5.29 (s, 2H), 3.59
(s, 2H); 13C NMR (CDCl3, 75 MHz) δ 164.7, 144.3, 142.9, 135.5,
129.1, 127.7, 126.2, 124.9, 123.7, 122.6, 118.1, 48.4, 30.8; ESI-MS m/z
301.1 (M + H)+; FT-HRMS (ESI) calcd for C15H12N2O3S (M + H)+
301.0641, found 301.0651.
gives the calculated relative energy profiles. R is the most stable
geometry of the anionic reactant, where an intramolecular C−
H···N H bond is essential to stabilize the anion. To undergo the
Smiles rearrangement, R must convert to its conformational
isomer, R′, which lies above R by 24.7 kJ/mol. TS1 denotes the
transition state in which the negatively charged nitrogen is
nucleophilically attacking the carbon atom, and its forward
product is IM1, a metastable intermediate located on the
potential energy surface, where the C−N bond has formed and
the C−S bond has been remarkably elongated but is not fully
broken. The overall barrier from R to IM1 is calculated to be
43.6 kJ/mol. Once formed, IM1 can be converted to the SR
product P1 via TS2 with a barrier of 36.4 kJ/mol. In TS2, the
new C−S bond is forming and the C−F bond becomes longer
to cleave from the C atom. Thus, our calculations indicate that
the SR pathway consists of two elementary steps, and the first
step is the rate-determining step.
Alternatively, if the reaction occurs via the direct nucleophilic
substitution pathway, the transition state involved is TS3, which
lies above the initial reactant by 66.0 kJ/mol. This pathway is
energetically less favorable by 22.4 kJ/mol than the SR
pathway. Thus, the reactant prefers to undergo the SR to
form product P1 rather than to carry out the direct nucleophilic
substitution to form product P2. The calculated results not only
give good support for the experimental observations but also
show the elementary-step mechanism of the reaction.
4-Benzyl-7-(trifluoromethyl)-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-
1
one (3d): 227 mg (70% yield), white solid; mp 61−63 °C; H NMR
(CDCl3, 300 MHz) δ 8.48 (dd, J = 0.9 Hz, 2.1, 1H), 7.85 (d, J = 2.1
Hz, 1H), 7.35 (dd, J = 1.8 Hz, 8.4, 2H), 7.25 (m, 1H), 7.19 (m, 2H),
5.47 (s, 2H), 3.56 (s, 2H); 13C NMR (CDCl3, 75 MHz) δ 164.7,
152.5, 142.8, 142.8, 137.1, 133.0, 128.4, 127.9, 127.3, 119.1, 45.7, 30.1,
29.7; ESI-MS m/z 325.1 (M + H)+; FT-HRMS (ESI) calcd for
C15H11F3N2OS (M + H)+ 325.0617, found 325.0644.
4-Methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-7-carbonitrile
1
(5a): 167 mg (82% yield), white solid; mp 115−116 °C; H NMR
(CDCl3, 300 MHz) δ 7.69 (m, 1H), 7.55 (m, 1H), 7.15 (d, J = 8.7 Hz,
1H), 3.48 (s, 3H), 3.46 (s, 2H); 13C NMR (CDCl3, 75 MHz) δ 165.0,
143.5, 131.6, 131.0, 124.7, 117.9, 117.7, 106.9, 32.1, 30.6; ESI-MS m/z
205.0 (M + H)+; FT-HRMS (ESI) calcd for C10H8N2OS (M + H)+
205.0430, found 205.0460.
4-Ethyl-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-7-carbonitrile
(5b): 192 mg (88% yield), white solid; mp 98−99 °C; 1H NMR
(CDCl3, 300 MHz) δ 7.66 (d, J = 1.8 Hz, 1H), 7.53 (dd, J = 2.1, 8.7
Hz, 1H), 7.19 (d, J = 8.7 Hz, 1H), 4.06 (q, J = 7.2, 6.9, 7.2 Hz, 2H),
3.42 (s, 2H), 1.29 (t, J = 7.2, 7.2 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ 164.1, 142.8, 131.9, 130.9, 125.1, 117.9, 117.5, 106.8, 40.3,
30.8, 12.9; ESI-MS m/z 219.1 (M + H)+; FT-HRMS (ESI) calcd for
C11H10N2OS (M + H)+ 219.0584, found 219.0575.
CONCLUSION
■
In conclusion, we have developed an operationally simple and
economic synthesis of a great number of benzo[1,4]thiazin-
3(4H)-ones based on the Smiles rearrangement. Furthermore,
to get a more in-depth understanding of the reaction
mechanism, we carried out quantum chemistry calculations
on a representative reaction. The theoretical results show that
the Smiles rearrangement pathway is energetically more
4-Isopropyl-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-7-carboni-
trile (5c): 151 mg (65% yield), white solid; mp 120−123 °C; 1H NMR
(CDCl3, 300 MHz) δ 7.70 (m, 1H), 7.51 (m, 1H), 7.28 (d, J = 8.4 Hz,
D
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1H), 4.65 (m, 1H), 3.33 (s, 2H), 1.54 (s, 3H), 1.52 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 166.2, 143.4, 132.2, 130.5, 127.4, 119.3, 117.9,
107.1, 51.8, 32.9, 20.4; ESI-MS m/z 233.1 (M + H)+; FT-HRMS
(ESI) calcd for C12H12N2OS (M + H)+ 233.0743, found 233.0756.
4-Butyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-7-carboni-
136.7, 135.0, 131.9, 130.6, 130.5, 130.0, 124.4, 120.1, 117.7, 107.4,
31.2; ESI-MS m/z 301.0 (M + H)+; FT-HRMS (ESI) calcd for
C15H9ClN2OS (M + H)+ 301.0197, found 301.0188.
ASSOCIATED CONTENT
1
■
trile (5d): 204 mg (83% yield), white solid; mp 75−76 °C; H NMR
S
* Supporting Information
(CDCl3, 300 MHz) δ 7.67 (d, J = 2.1 Hz, 1H), 7.53 (dd, J = 1.8, 8.7
Hz, 1H), 7.18 (d, J = 8.7 Hz, 1H), 4.02 (t, J = 7.5, 7.5 Hz, 2H), 3.42 (s,
2H), 1.60 (m, 2H), 1.35 (m, 2H), 0.93 (m, 2H); 13C NMR (CDCl3,
75 MHz) δ 164.3, 142.7, 131.9, 130.9, 125.3, 117.9, 117.9, 106.7, 44.6,
30.9, 29.4, 19.9, 13.7; ESI-MS m/z 247.1 (M + H)+; FT-HRMS (ESI)
calcd for C13H14N2OS (M + H)+ 247.0900, found 247.0902.
Figures, tables, and a CIF file giving H NMR and 13C NMR
1
spectra of all compounds, X-ray datea for 5a, and the Cartesian
coordinates and absolute energies for all structures involved in
theoretical calculations. This material is available free of charge
via the Internet at http://pubs.acs.org.
3-Oxo-4-phenethyl-3,4-dihydro-2H-benzo[b][1,4]thiazine-7-car-
1
bonitrile (5e): 229 mg (78% yield), yellow solid; mp 92−93 °C; H
AUTHOR INFORMATION
Corresponding Author
*E-mail: chenma@sdu.edu.cn; zhangdj@sdu.edu.cn.
■
NMR (CDCl3, 300 MHz) δ 7.63 (d, J = 1.8 Hz, 1H), 7.47 (dd, J = 2.1,
8.7 Hz, 1H), 7.30 (m, 1H), 7.22 (m, 4H), 7.09 (d, J = 8.4 Hz, 1H),
4.23 (t, J = 7.5, 1.8 Hz, 2H), 3.41 (s, 2H), 2.63 (t, J = 7.8, 7.5 Hz, 2H);
13C NMR (CDCl3, 75 MHz) δ 164.2, 142.8, 137.7, 131.9, 130.9, 128.8,
Notes
128.7, 126.9, 125.4, 117.9, 106.9, 46.6, 33.7, 30.9; ESI-MS m/z 295.1
(M + H)+; FT-HRMS (ESI) calcd for C17H14N2OS (M + H)+
295.0900, found 295.0896.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
4-(3,4-Dimethoxyphenethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]-
thiazine-7-carbonitrile (5f): 188 mg (53% yield), white solid; mp
177−179 °C; 1H NMR (CDCl3, 300 MHz) δ 7.64 (d, J = 1.8 Hz, 1H),
7.49 (dd, J = 2.1, 8.7 Hz, 1H), 7.12 (d, J = 8.7 Hz, 1H), 6.77 (d, J = 8.7
Hz, 1H), 6.71 (m, 2H), 4.22 (m, 2H), 3.86 (s, 3H), 3.85 (s, 3H), 3.407
(s, 2H), 2.89 (t, J = 7.8, 7.5 Hz, 2H); 13C NMR (CDCl3, 75 MHz) δ
164.3, 149.1, 148.0, 142.7, 131.9, 130.9, 130.2, 125.5, 120.8, 117.9,
117.8, 112.1, 111.5, 106.9, 55.9, 46.5, 33.3, 30.9; ESI-MS m/z 355.1
(M + H)+; FT-HRMS (ESI) calcd for C19H18N2O3S (M + H)+
355.1110, found 355.1105.
3-Oxo-4-phenyl-3,4-dihydro-2H-benzo[1,4]thiazine-7-carboni-
trile (5g): 234 mg (88% yield), white solid; mp 158−160 °C; 1H NMR
(CDCl3, 300 MHz) δ 7.68 (d, J = 1.8 Hz, 1H), 7.49 (m, 3H) 7.28 (dd,
J = 1.8, 8.4 Hz, 1H), 7.21 (m, 2H), 6.55 (d, J = 8.7 Hz, 1H), 3.58 (s,
2H); 13C NMR (CDCl3, 75 MHz) δ 164.3, 144.4, 138.3, 131.7, 130.5,
130.2, 129.0, 128.6, 124.2, 120.2, 117.9, 107.0, 31.1; ESI-MS m/z
267.1 (M + H)+; FT-HRMS (ESI) calcd for C15H10N2OS (M + H)+
267.0587, found 267.0591.
We wish to thank the National Natural Science Foundation of
China (Nos. 21172131 and 21273131) for financial support of
this research.
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1
trile (5h): 220 mg (78% yield), yellow solid; mp 296−297 °C; H
NMR (CDCl3, 300 MHz) δ 7.69 (d, J = 1.8 Hz, 1H), 7.30 (m, 3H),
7.08 (m, 2H), 7.02 (d, J = 8.7 Hz, 1H), 3.61 (s, 2H), 2.43 (s, 3H); 13C
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7-carbonitrile (5i): 217 mg (73% yield), brown solid; mp 192−194
1
°C; H NMR (CDCl3, 300 MHz) δ 7.68 (d, J = 1.8 Hz, 1H) 7.3 (m,
1H), 7.11 (dd, J = 2.1, 9.0 Hz, 2H), 7.02 (d, J = 9.0 Hz, 2H), 6.61 (d, J
= 8.4 Hz, 1H), 3.86 (s, 3H), 3.61 (s, 2H); 13C NMR (CDCl3, 75
MHz) δ 164.5, 159.7, 144.6, 131.7, 130.6, 130.5, 129.6, 124.0, 120.1,
117.9, 115.5, 106.9, 55.6, 31.1; ESI-MS m/z 297.1 (M + H)+; FT-
HRMS (ESI) calcd for C16H12N2O2S (M + H)+ 297.0692, found
297.0684.
4-(4-Fluorophenyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-7-
carbonitrile (5j): 148 mg (52% yield), yellow solid; mp 267−269 °C;
1H NMR (CDCl3, 300 MHz) δ 7.70 (d, J = 1.8 Hz, 1H), 7.32 (dd, J =
1.8, 8.7 Hz, 1H), 7.21 (m, 4H), 6.57 (d, J = 8.4 Hz, 1H), 3.61 (s, 2H);
13C NMR (CDCl3, 75 MHz): δ 164.3 (d, J = 22.5 Hz, 1C), 160.8,
144.2, 134.1 (d, J = 1.5 Hz, 1C), 131.8, 130.5 (d, J = 4.5 Hz, 1C),
130.4, 124.3, 120.1, 117.8, 117.5, 117.1, 107.3, 31.1, 29.7; ESI-MS m/z
285.0 (M + H)+; FT-HRMS (ESI) calcd for C15H9FN2OS (M + H)+
285.0492, found 285.0482.
4-(4-Chlorophenyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-7-
carbonitrile (5k): 159 mg (53% yield), brown solid; mp 312−315 °C;
1H NMR (CDCl3, 300 MHz) δ 7.71 (d, J = 1.5 Hz, 1H), 7.50 (d, J =
8.4 Hz, 2H), 7.33 (dd, J = 1.5, 8.4 Hz, 1H), 7.15 (d, J = 8.7 Hz, 2H),
6.58 (d, J = 8.7 Hz, 1H); 13C NMR (CDCl3, 75 MHz) δ 164.3, 144.0,
E
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