Controllable construction of isoquinolinedione and isocoumarin scaffolds: Via RhIII-catalyzed C-H annulation of N -tosylbenzamides with diazo compounds

Article abstract of DOI:10.1039/c9ob01789e

A highly efficient protocol for the synthesis of isoquinolinediones by Rh^III-catalyzed C-H activation/annulation/decarboxylation of N-tosylbenzamides with diazo compounds is reported. The switchable synthesis of isocoumarins was also achieved successfully via C-H activation/annulation with slight modification of the reaction conditions. Importantly, the synthetic utility of this new reaction was further demonstrated in an atom-economical and operationally convenient total synthesis of a TDP2 inhibitor derivative from commercially available starting materials.

Full text of DOI:10.1039/c9ob01789e

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DOI: 10.1039/C9OB01789E
Journal Name
ARTICLE
Controllable Construction of Isoquinolinedione and Isocoumarin
Scaffolds via RhIII-Catalyzed C-H Annulation of N-tosylbenzamides
with Diazo Compounds
Received 00th January 20xx,
Accepted 00th January 20xx
Yanfei Liu, Jiaping Wu,* Baiyang Qian and Yongjia Shang*
DOI: 10.1039/x0xx00000x
A
highly efficient protocol for synthesis of isoquinolinediones by RhIII-catalyzed C-H
www.rsc.org/
activation/annulation/decarboxylation of N-tosylbenzamides with diazo compounds is reported. The
switchable synthesis of isocoumarins was also achieved successfully via C-H activation/annulation with the
slight modification of the reaction conditions. Importantly, the synthetic utility of this new reaction was
further demonstrated in an atom-economical and operationally convenient total synthesis of TDP2 inhibitor
derivative from the commercially available starting materials.
Introduction
Isoquinolinedione and isocoumarin, serving as important
heterocyclic scaffolds, are occurring ubiquitously in many natural
products and biologically active molecules which exhibit antifungal,
anti-inflammatory, cytotoxic, and other biological activities (Scheme
1a).1 Therefore, the great attention has been devoted to the
development of highly efficient strategies for their synthesis.2
Traditionally, the methods toward the synthesis of these precious
structures mainly include: 1) the cyclization of 1,2-difunctionalized
arenes with alkynes or CO;3 2) the amidation of homophthalic acid
or anhydride derivatives.4 In spite of these tremendous advances in
this research area, the general involvement of multistep procedures,
sometimes harsh reaction conditions, and the requirement of
prefunctionalized starting materials that are not readily available,
make their application limited. In this regard, the establishment of
general and straightforward synthetic routes with less waste is
highly desirable.
Scheme 1 Importance of isoquinolinediones and isocoumarins
For recent years, the transition-metal catalyzed C-H
functionalization has emerged as
a powerful tool for the
reaction development and process efficiency, modulating the
chemoselectivity outcome of synthetic transformations by fine-
tuning of reaction parameters would be a much more appealing,
yet challenging task.11 In this context, the practical substrate
modifications have been widely utilized to drive the reaction to the
desired chemoselective pathway.12 Thus, broadly applicable
catalytic C-H transformations that display substrate-controllable
chemodivergency13 are in much demand, particularly as a means to
accelerate the screening process and structure-activity relationship
studies in drug discovery. Nevertheless, to the best of our
acknowledgement, the highly efficient divergent synthesis of
isocoumarins and isoquinolinediones in the same catalytic C-H
activation system has not been achieved to date. As our continuing
efforts toward the construction of functional heterocycles via C-H
construction of heterocyclic motifs due to its nature of atom- and
step-economy.5 Actually, Rh(III)-catalyzed C-H annulation of
aromatic substrates with diverse coupling partners have provided a
number of efficient pathways to access the isocoumarin
derivatives,6,7,8 though the application of catalytic C-H activation
strategy to construct isoquinolinediones has been seldom
reported.9,10 Additionally, each aforementioned reaction just gave a
single heterocyclic structure with the lack of ability for the
switchable synthesis of other heterocycles. From the perspective of
Key Laboratory of Functional Molecular Solids (Ministry of Education), Anhui Key
Laboratory of Molecular Based Materials, College of Chemistry and Materials
Science, Anhui Normal University, Wuhu 241002, China.
E-mail: wujiaping@ahnu.edu.cn; shyj@mail.ahnu.edu.cn
activation,14 we herein disclose
a
switchable access to
† Electronic Supplementary Information (ESI) available: Experimental procedures,
characterization data, and 1H and 13C NMR charts. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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isoquinolinedione and isocoumarin cores through tandem Rh(III)- toluene (Table 1, entries 1-7), and the absolute configuration of the
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catalyzed C-H activation/annulation of N-tosylbenzamides with product 3a was confirmed by X-ray analysisD(OScI:h1e0m.10e329)/.CT9hOeBn0,17w8i9thE
divers diazo compounds, by tolerating a wide range of functional 1.1 eq H2O or 1.0 eq TFA as the additive, the corresponding product
groups (Scheme 1b). Furthermore, the present catalytic system could be isolated in 46% and 42% yields, respectively (Table 1,
might be applied successfully to the synthesis of complex molecules entries 8 and 9). Gratifyingly, the combination of 1.1 eq H2O or 1.0
with bioactivities.
eq TFA as the additive improved the reaction efficiency significantly
to give the desired product in 61% yield (Table 1, entry 10). Other
acids, such as PivOH, TsOH, B(OH)3, HCO2H, were also examined, by
failing to give the better results (Table 1, entries 11-14).
Unexpectedly, when the reaction was conducted in DCE, the
efficiency could be improved furtherly to furnish the desired
product in 71% yield (Table 1, entry 15). It was also found that a less
loading amount of TFA could give a better result (Table 1, entry 16).
Unfortunately, the attempt to get a higher reactivity by modifying
the ratio of H2O and TFA was not effective (Table 1, entries 17 and
18). Besides, various directing groups were also investigated, by
suggesting TsNH group the optimal choice. Thus, the following
conditions were eventually established for subsequent studies:
Results and discussion
Table 1 Optimization of reaction conditions a
entry
1
additiveb
solvent
yield (%)c
44
_
Toluene
DCE
2
_
_
32
3
THF
Dioxane
MeCN
DCM
19
o
[Cp*RhCl2]2 (2.5 mol%), H2O (1.1 eq), TFA (0.5 eq) in DCE at 110 C
under Ar for 24 h.
4
_
15
5
_
22
Table 2 Synthesis of isoquinoline diones a,b
6
_
34
7
_
EtOAc
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
DCE
41
8
H2O
46
9
TFA
42
10
11
12
13
14
15
16d
17e
18f
H2O, TFA
H2O, PivOH
H2O, TsOH)
H2O, B(OH)3
H2O, HCO2H
H2O, TFA
H2O, TFA
H2O, TFA
H2O, TFA
61
47
50
50
60
71
DCE
77
DCE
52
DCE
51
a The reaction was conducted using 1a (0.1 mmol), 2a (0.3 mmol), [Cp*RhCl2]2
(2.5 mol%) in solvent (1.0 mL) at 110 oC under Ar for 24 h. b Unless otherwise
c
noted, H2O (1.1 eq), Acid (1.0 eq).
Isolated yield by flash column
chromatography based on 1a. d H2O (1.1 eq), TFA (0.5 eq). e H2O (1.1 eq), TFA
f
(2.0 eq). H2O (1.1 eq), TFA (0.2 eq).
a Unless otherwise noted, the reaction was conducted using 1 (0.1 mmol), 2a (0.3
mmol), [Cp*RhCl2]2 (2.5 mol%), H2O (1.1 equiv), TFA (0.5 equiv) in DCE at 110
oC under Ar for 24 h. b Isolated yield by flash column chromatography based on 1.
Scheme 2 ORTEP drawing of isoquinolinedione 3a
Our studies began with the reaction of N-tosylbenzamide 1a and
diethyl 2-diazomalonate 2a in the presence of 2.5 mol% [Cp*RhCl2]2
and the results were summarized in Table 1 (more details in the
supporting information). With the screening of various solvents,
such as toluene, DCE, THF, dioxane, MeCN, DCM and EtOAc, the
isoquinolinedione derivative 3a was obtained in 44% yield in
To explore the scope and generality of this reaction, a number of
substituted N-tosylbenzamides were employed under the optimal
reaction conditions as shown in Table 2. What’s confusing us is
neither electron-donating group nor electron-withdrawing group
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bearing on the para position of the phenyl ring could not be able to good yields (4b-4m). Especially, the strong electron-withdrawing
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DOI: 10.1039/C9OB01789E
form the desired products very well (3b-3d). To override this groups (-CF3, -COMe, -CO2Me) substituted amides were compatible
limitation, a number of ortho-substituted N-toyslbenzamides were with the catalytic system to afford the corresponding products in up
employed in the reaction, and the reaction efficiency was found to to 84% yield (4e-4g). The occurrence of halogen in the products
be improved as expected with the well tolerance of various would provide a chance for the synthesis of complex functional
functional groups, by affording the corresponding products in molecules by further cross-couplings (4i, 4j, 4l and 4m). Moreover,
moderate to good yields (3e-3k). Notably, N-toyslbenzamide N-tosylbenzo[d][1,3]dioxole-5-carboxamide and 2-naphthyl amide
bearing the strong electron-withdrawing group o-CF3 could be could also conduct this reaction smoothly to generate the
tolerated in the reaction, and the desired product was isolated in corresponding products (4n and 4o) in 60% and 92% yields,
81% yield (3l). Besides, due to the steric hindrance derived from respectively. Interestingly, the alkylated product was obtained via
meta-substitution, the highly regioselectivity and moderate yields alkylation/decarboxylation when 3-furyl amide was employed in the
were obtained by employment of meta-substituted N- standard conditions, giving rise to the methyl ketone derivative (4p).
toyslbenzamides (3m-3p). Finally, it was surprisingly found that 2- Unfortunately, the ortho-substituted N-toyslbenzamides failed to
thienylamide did not undergo the decarboxylation procedure, thus participate in this reaction (4q-4s).
generating the thieno[2,3-c]pyridin-7(6H)-one derivative in 41%
yield instead (3q).
Table 4 Substrate scope of diazo compounds a,b
Table 3 Substrate scope of amides a,b
a Unless otherwise noted, the reaction was conducted using 1a (0.1 mmol), 2 (0.3
mmol), [Cp*RhCl2]2 (2.5 mol%) in MeOH/H2O (1 mL, v/v = 10:1) at 60 oC under
Ar for 24 h. b Isolated yield by flash column chromatography based on 1.
Meanwhile, various diazo compounds as the precursor of carbine
were selected for the further investigation, and the results were
summarized as shown in Table 4. To our delight, the P-containing
diazo exhibited high reactivity to afford the desired product in good
to excellent yields (4t and 4u), which provides an access to the P-
containing heterocyclic compounds. And cyclic 2-diazo-1,3-diketone
was competent substrate for this reaction, then forming the
benzo[c]chromene-1,6(2H)-dione in 96% yield (4v). Notably, the
diazo generated from 1-arylpropan-2-ones were also able to
participate in the reaction to deliver the corresponding products in
moderate to good yields (4w-4y), albeit a lower yield was obtained
by use of 1-diazo-1-(4-fluorophenyl)propan-2-one (4z).
a Unless otherwise noted, the reaction was conducted using 1 (0.1 mmol), 2b (0.3
mmol), [Cp*RhCl2]2 (2.5 mol%) in MeOH/H2O (1 mL, v/v = 10:1) at 60 oC under
Ar for 24 h. b Isolated yield by flash column chromatography based on 1.
To verify the synthetic utility of this transformation, its
application for the total synthesis of TDP2 inhibitor derivative15
from the commercially available starting materials was realized, by
giving the desired product 9 in 46% yield in the final step (Scheme
3).16-19 Besides, the scalable synthesis of isocoumarins was also
carry out. As shown in Scheme 4, when the reaction of 1a was
scaled up to 4 mmol, the corresponding product 4a was isolated in
68% yield, albeit only 0.55 g scale has been achieved.
Interestingly, with the slight modification of the former
conditions, the unexpected isocoumarin (4a) was obtained in 77%
yield by use of 3-diazopentane-2,4-dione (2b). After that, we turned
to evaluating the amide scope of this protocol as shown in Table 3.
No electronic effect was exhibited in this reaction, and various
functional groups, no matter electron-donating or electron-
withdrawing groups bearing on the phenyl rings of amides, were
well tolerated, by furnishing the targeted products in a moderate to
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In summary, we have presented the tandem RhIII-catalyzed C-H
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activation/annulation or C-H activation/annDulOaIt:io10n./1d03e9c/aCr9bOoxBy0l1a7t8io9nE
of N-tosylbenzamides with diazo compounds. In this reaction, the
isocoumarins and isoquinolinediones could be controllable
synthesis depending on the choice of the diazo compounds with the
slight modification of reaction conditions. The tolerance of a wide
range of readily available amides and diazo compounds and the
scalable application make this reaction a promising avenue for the
construction of valuable heterocycles. So the further studies for the
extended synthetic applications of this catalytic system are ongoing
in our laboratory.
Experimental Section
General Information
Scheme 3 Synthetic application for TDP2 inhibitor derivative
All reactions were carried under Ar atmosphere unless otherwise
noted. All chemicals were used without further purification as
commercially available. Reactions were monitored by using thin-
layer chromatography (TLC) on commercial silica gel plates (GF 254).
1
NMR (500 MHz or 400 MHz for H NMR, 125 MHz or 100 MHR for
13C NMR) spectra were recorded in CDCl3 with TMS as the internal
Scheme 4 Gram-scale synthesis of isocoumarin
standard unless otherwise noted. Chemical shifts (δ) were reported
in ppm referenced to the CDCl3 residual peak (δ 7.28) for H NMR.
1
Based on our experimental results and the previous researches,20
a plausible mechanism for this reaction was depicted in Scheme 5.
Initial coordination of N-tosylbenzamide 1 to [RhIIICp*] species
afford A, which can coordinate 1 equiv of diazo compound 2a or 2b
to form intermediate B or E presumably through the Rh-carbene
formation pathway. Subsequent protonation of B or E furnishes C or
F. A further protonation of C to release RhIIICp* catalyst and form D,
which could generate the isoquinolinediones 3 via the subsequent
annulation and decarboxylation. On the other hand, the
Chemical shifts of 13C NMR were reported relative to CDCl3 (δ 77.0).
The following abbreviations were used to describe peak splitting
patterns when appropriate: singlet (s), doublet (d), triplet (t),
quartet (q), multiplet (m). Coupling constant, J, was reported in
Hertz unit (Hz). High-resolution mass spectra (HRMS) analysis was
measured using ESI techniques. The melting points were measured
using X-4 melting point apparatus.
General procedure for the preparation of isoquinolinediones
A reaction tube charged with N-tosylcarboxamide (0.1 mmol),
[Cp*RhCl2]2 (2.5 mol%, 1.6 mg）and stir bar. H2O (1.1 eq, 2.0 μL),
TFA (50 mol%, 3.7μL) was added via microsyringe and diazo
compounds (0.3 mmol) was added via syringe in the solvent DCE
protonation of
F occurred to deliver the direct alkylated
intermediate G, which undergoes a keto-enol tautomerization and
lactonzation sequence to give the product 4 via C-N cleavage.
o
(2.0 mL) under Ar. After that, the mixture was stirred at 110 C for
24 h. The pure product was obtained by flash column
chromatography (silica gel) eluting by petroleum ether/ethyl
acetate 6:1 to 3:1.
General procedure for the preparation of isocoumarins
A reaction tube was charged with N-tosylcarboxamide (0.1 mmol),
[Cp*RhCl2]2 (2.5 mol%, 1.6 mg）and stir bar. Diazo (0.3 mmol) was
added via syringe in the solvent MeOH/H2O 10:1 under Ar. After
that, the mixture was stirred at 60 oC for 24 h under Ar and
monitored by TLC. The pure product was obtained by flash column
chromatography (silica gel) eluting by petroleum ether/ethyl
acetate 15:1 to 10:1.
General procedure for the preparation of TDP2 inhibitor derivative
3-Bromoaniline 5 (5 mmol) was suspended in CH2Cl2 (15 mL) and
cooled in an ice bath. Pyridine (15 mmol) and methylsulfonyl
chloride (5.5 mmol) were added. The resulting mixture was allowed
to warm to ambient temperature. The reaction was monitored by
TLC, when a complete conversion of the starting material was
observed, 1M HCl (aq.) was added and washed with DCM. The
combined organic phase was then dried on NaSO4, filtered and
Scheme 5 Mechanistic hypothesis
Conclusions
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evaporated. The residue was purified by passing through a pad of δ 168.6, 167.2, 163.6, 163.2, 146.1, 139.3, 137.4, V1ie3w5A.r8ti,cle1O2n9l.in8e,
silica gel eluting with petroleum ether / ethyl acetate 2:1 to afford 6 117.5, 117.2, 111.8, 62.3, 56.1, 55.8, 40.5,D2O2I.:21,0.11043.59./CH9ROMB0S17(E8S9IE)
as pink solid in 96% yield.16,17
m/z: [M+H]+ Calcd for C24H26NO9S 504.1323; Found 504.1328.
A 25 mL reaction tube was charged with N-Ms-3-Bromoaniline 6 (2 Diethyl
2-(6-bromo-1,3-dioxo-2-tosyl-1,2,3,4-
mmol), 3-Carboxyphenylboronic (4 mmol), tetra tetrahydroisoquinolin-8-yl)malonate (3d): This compound was
(triohenylphosphine) palladium (5 mol%), K2CO3 (aq, 10mmol) in purified by column chromatography to afford a white solid in 25%
o
DMF (6 mL) was stired at 100 oC for 2 h under Ar. And then the yield (14 mg); Melting point: 145-148 C. 1H NMR (400 MHz, CDCl3)
reaction was quenched with 1M HCl, the solution was extracted δ 8.18-8.16 (m, 2H), 7.53-7.52 (m, 1H), 7.42-7.41 (m, 1H), 7.37-7.34
with DCM. The combined organic phase was then dried on NaSO4, (m, 2H), 5.71 (s, 1H), 4.27 (q, J = 7.2 Hz, 4H), 4.03 (s, 2H), 2.45 (s, 3H),
filtered and evaporated. The residue was purified by passing 1.30 (t, J = 7.2 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ 167.7, 165.8,
through a pad of silica gel eluting with petroleum ether / ethyl 162.9, 146.1, 138.0, 135.6, 135.0, 133.1, 130.5, 129.6, 129.5, 129.0,
acetate 1:1 to afford 7 as yellow solid in 60% yield.18
123.8, 62.3, 55.0, 39.2, 21.8, 14.1. HRMS (ESI) m/z: [M+H]+ Calcd for
To a solution of the 3-(3-N-Ms) phenyl benzoic acid 7 (0.5 mmol) in C23H23BrNO8S 552.0322; Found 552.0314.
THF (5 mL) were sequentially added TsNCO (0.75 mmol) and Et3N 8-Methyl-2-tosylisoquinoline-1,3(2H,4H)-dione
(3e):
This
(0.75 mmol) at room temperature. After being stirred at 60 oC for 4 compound was purified by column chromatography to afford a
h, the reaction mixture was cooled to room temperature and the white solid in 83% yield (27 mg); Melting point: 183-185 oC. 1H NMR
solution was removed by rotary evaporator. The residue was (400 MHz, CDCl3) δ 8.24-8.22 (m, 2H), 7.45-7.37 (m, 3H), 7.23 (d,
diluted with DCM and washed with 1M HCl. The combined organic J=7.6 Hz, 1H), 7.07 (d, J=7.6 Hz, 1H), 4.04 (s, 2H), 2.68 (s, 3H), 2.46 (s,
phase was then dried on NaSO4, filtered and evaporated. The 3H). 13C NMR (100 MHz, CDCl3) δ 167.3, 163.3, 145.8, 142.9, 135.5,
residue was purified by passing through a pad of silica gel eluting 133.7, 133.4, 131.7, 129.6, 129.4, 125.4, 124.7, 39.8, 22.7, 21.8.
with petroleum ether / ethyl acetate 1:1 to afford 8 as white solid in HRMS (ESI) m/z: [M+H]+ Calcd for C17H16NO4S 330.0795; Found
90% yield.19
330.0803.
A reaction tube charged with 3-(3-N-Ms) phenyl benzamide 8 (0.1 8-Ethyl-2-tosylisoquinoline-1,3(2H,4H)-dione (3f): This compound
mmol), [Cp*RhCl2]2 (2.5 mol%, 1.6 mg）and stir bar. H2O (1.1 eq, was purified by column chromatography to afford a white solid in
o
1
2.0 μL), TFA (50 mol%, 3.7 μL) was added via microsyringe and diazo 65% yield (22 mg); Melting point: 154-156 C. H NMR (400 MHz,
compounds (0.3 mmol) was added via syringe in the solvent DCE CDCl3) δ 8.24-8.22 (m, 2H), 7.46 (t, J=7.6 Hz, 1H), 7.38 (d, J=8.0 Hz,
o
(2.0 mL) under Ar. After that, the mixture was stirred at 110 C for 2H), 7.28-7.26 (m, 2H), 7.07 (d, J=7.6 Hz, 1H), 4.00 (s, 2H), 3.11-3.05
24 h. The pure product was obtained by flash column (m, 2H), 2.46 (s, 3H), 1.26-1.23 (m, 3H). 13C NMR (100 MHz, CDCl3) δ
chromatography (silica gel) eluting by petroleum ether/ethyl 167.0, 163.3, 148.5, 145.8, 135.5, 133.5, 130.1, 129.6, 129.4, 125.3,
acetate 3:1 to 2:1 to afford 9 as white solid in 46% yield.
Diethyl 2-(1,3-dioxo-2-tosyl-1,2,3,4-tetrahydroisoquinolin-8- C18H18NO4S 344.0951; Found 344.0947.
yl)malonate (3a): This compound was purified by column 8-Methoxy-2-tosylisoquinoline-1,3(2H,4H)-dione
124.9, 39.7, 27.8, 21.8, 15.4. HRMS (ESI) m/z: [M+H]+ Calcd for
(3g):
This
chromatography to afford a white solid in 77% yield (36 mg); compound was purified by column chromatography to afford a
Melting point: 119-121 oC. 1H NMR (500 MHz, CDCl3) δ 8.19-8.16 (m, white solid in 51% yield (18 mg); Melting point: 186-188 oC. 1H NMR
2H), 7.59-7.55 (m, 1H), 7.39-7.34 (m, 3H), 7.24-7.22 (m, 1H), 5.75 (s, (400 MHz, CDCl3) δ 8.26-8.24 (m, 2H), 7.53-7.49 (m, 1H), 7.37-7.35
1H), 4.28-4.23 (m, 4H), 4.05 (s, 2H), 2.44 (s, 3H), 1.31-1.27 (m, 6H). (m, 2H), 6.95-6.93 (m, 1H), 6.80-6.77 (m, 1H), 4.01 (s, 2H), 3.96 (s,
13C NMR (125 MHz, CDCl3) δ 168.2, 166.5, 163.4, 145.9, 136.3, 135.3, 3H), 2.44 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 166.9, 161.1, 160.7,
134.1, 133.7, 129.7, 129.5, 127.6, 124.9, 62.0, 55.3, 39.7, 21.8, 14.0. 145.7, 135.5, 135.3, 135.2, 129.6, 129.5, 119.1, 115.1, 111.1, 56.3,
HRMS (ESI) m/z: [M+H]+ Calcd for C23H24NO8S 474.1217; Found 39.4, 21.8. HRMS (ESI) m/z: [M+H]+ Calcd for C17H16NO5S 346.0744;
474.1211.
Found 346.0741.
Diethyl
2-(6-methyl-1,3-dioxo-2-tosyl-1,2,3,4- 8-Phenyl-2-tosylisoquinoline-1,3(2H,4H)-dione
(3h):
This
tetrahydroisoquinolin-8-yl)malonate (3b): This compound was compound was purified by column chromatography to afford a
purified by column chromatography to afford a white solid in 54% white solid in 45% yield (18 mg); Melting point: 140-142 oC. 1H NMR
o
yield (26 mg); Melting point: 56-58 C. 1H NMR (400 MHz, CDCl3) δ (400 MHz, CDCl3) δ 8.14-8.12 (m, 2H), 7.56 (t, J=7.6 Hz, 1H), 7.46-
8.19-8.16 (m, 2H), 7.36-7.34 (m, 2H), 7.15 (s, 1H), 7.03 (s, 1H), 5.74 7.38 (m, 3H), 7.34-7.28 (m, 5H), 7.23-7.21 (m, 1H), 4.03 (s, 2H), 2.43
(s, 1H), 4.26 (q, J = 7.2 Hz, 4H), 4.02 (s, 2H), 2.44 (s, 3H), 2.39 (s, 3H), (s, 3H). 13C NMR (100 MHz, CDCl3) δ 166.5, 162.9, 145.8, 144.4,
1.31-1.28 (m, 6H). 13C NMR (100 MHz, CDCl3) δ 168.4, 166.8, 163.3, 139.8, 135.3, 133.0, 132.9, 131.4, 129.5, 129.5, 128.6, 128.3, 127.8,
145.8, 145.1, 136.3, 135.4, 134.3, 130.7, 129.5, 128.1, 122.1, 62.0, 126.3, 125.8, 39.3, 21.8. HRMS (ESI) m/z: [M+H]+ Calcd for
55.3, 39.7, 21.8, 21.8, 14.1. HRMS (ESI) m/z: [M+H]+ Calcd for C22H18NO4S 392.0951; Found 392.0959.
C24H26NO8S 488.1374; Found 488.1382.
8-Fluoro-2-tosylisoquinoline-1,3(2H,4H)-dione (3i): This compound
Diethyl
2-(6-methoxy-1,3-dioxo-2-tosyl-1,2,3,4- was purified by column chromatography to afford a white solid in
tetrahydroisoquinolin-8-yl)malonate (3c): This compound was 56% yield (19 mg); Melting point: 185-187 oC. 1H NMR (400 MHz,
purified by column chromatography to afford a white solid in 31% CDCl3) δ 8.25-8.21 (m, 2H), 7.59-7.54 (m, 1H), 7.39-7.37 (m, 2H),
yield (16 mg); Melting point: 142-144 C. 1H NMR (400 MHz, CDCl3) 7.15-7.10 (m, 1H), 7.07-7.04 (m, 1H), 4.10 (s, 2H), 2.45 (s, 3H). 13
C
o
δ 8.18-8.16 (m, 2H), 7.36-7.33 (m, 2H), 6.88 (d, J = 2.4 Hz, 1H), 6.66 - NMR (100 MHz, CDCl3) δ 166.6, 162.8 (d, J=267.2 Hz), 159.4 (d,
6.65 (m, 1H), 5.78 (s, 1H), 4.25 (q, J = 7.2 Hz, 4H), 4.04 (s, 2H), 3.85 J=4.8 Hz), 146.0, 135.8 (d, J=10.2 Hz), 135.2, 135.0, 129.6 (d, J=8.2
(s, 3H), 2.44 (s, 3H), 1.29 (t, J = 7.2 Hz, 6H). 13C NMR (125 MHz, CDCl3) Hz), 123.2 (d, J=4.3 Hz), 116.7, 116.5, 114.8 (d, J=6.4 Hz), 39.4 (d,
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Organic & Biomolecular Chemistry
Page 6 of 9
COMMUNICATION
Journal Name
J=2.6 Hz), 21.8. HRMS (ESI) m/z: [M+H]+ Calcd for C16H13FNO4S (400 MHz, CDCl3) δ 8.24-8.21 (m, 2H), 7.39-7.36 (m, 2H), 7.03 (s, 1H),
View Article Online
334.0544; Found 334.0541.
6.87 (s, 1H), 4.00 (s, 2H), 2.63 (s, 3H), 2.45 D(sO,I3: 1H0).,1023.39/5C(9sO, B30H1)7.8193EC
8-Chloro-2-tosylisoquinoline-1,3(2H,4H)-dione (3j): This compound NMR (100 MHz, CDCl3) δ 167.6, 163.2, 145.6, 144.5, 143.0, 135.7,
was purified by column chromatography to afford a white solid in 133.9, 132.7, 129.6, 129.4, 125.9, 122.0, 39.8, 22.6, 21.8, 21.5.
40% yield (14 mg); Melting point: 208-210 oC. 1H NMR (400 MHz, HRMS (ESI) m/z: [M+H]+ Calcd for C18H18NO4S 344.0951; Found
CDCl3) δ 8.26-8.22 (m, 2H), 7.50-7.44 (m, 2H), 7.40-7.38 (m, 2H), 344.0955.
7.17-7.14 (m, 1H), 4.04 (s, 2H), 2.46 (s, 3H). 13C NMR (100 MHz, Ethyl 5-hydroxy-7-oxo-6-tosyl-6,7-dihydrothieno[2,3-c]pyridine-4-
CDCl3) δ 166.0, 160.7, 146.0, 136.2, 135.2, 135.2, 133.9, 131.6, carboxylate (3q): This compound was purified by column
129.7, 129.6, 126.0, 124.2, 39.5, 21.8. HRMS (ESI) m/z: [M+H]+ Calcd chromatography to afford a white solid in 41% yield (16 mg);
for C16H13ClNO4S 350.0248; Found 350.0242.
Melting point: decomposition. 1H NMR (400 MHz, CDCl3) δ 12.35 (s,
8-Bromo-2-tosylisoquinoline-1,3(2H,4H)-dione
(3k):
This 1H), 8.15-8.12 (m, 2H), 7.86 (dd, J=5.2 Hz, J=13.6 Hz, 2H), 7.41-7.39
compound was purified by column chromatography to afford a (m, 2H), 4.56-4.50 (m, 2H), 2.46 (s, 3H), 1.51 (t, J = 7.2 Hz, 3H). 13
C
white solid in 60% yield (24 mg); Melting point: 222-225 oC. 1H NMR NMR (100 MHz, CDCl3) δ 170.2, 165.0, 153.9, 149.8, 146.0, 136.6,
(400 MHz, CDCl3) δ 8.26-8.23 (m, 2H), 7.73-7.71 (m, 1H), 7.40-7.36 133.5, 129.7, 129.7, 125.0, 119.0, 99.0, 62.6, 21.9, 14.3.HRMS (ESI)
(m, 3H), 7.22-7.19 (m, 1H), 4.04 (s, 2H), 2.46 (s, 3H). 13C NMR (100 m/z: [M+H]+ Calcd for C17H16NO6S2 394.0414; Found 394.0407.
MHz, CDCl3) δ 165.8, 161.1, 146.1, 135.3, 135.2, 135.1, 134.0, 129.7, 4-Acetyl-3-methyl-1H-isochromen-1-one (4a): This compound was
129.6, 126.7, 125.7, 123.8, 39.5, 21.9. HRMS (ESI) m/z: [M+H]+ Calcd purified by column chromatography to afford a white solid in 77%
o
1
for C16H13BrNO4S 393.9743; Found 393.9741.
yield (16 mg); Melting point: 97-99 C. H NMR (500 MHz, CDCl3) δ
2-Tosyl-8-(trifluoromethyl)isoquinoline-1,3(2H,4H)-dione (3l): This 8.33-8.31 (m, 1H), 7.76-7.70 (m, 1H), 7.56-7.50 (m, 1H), 7.33 (d, J =
compound was purified by column chromatography to afford a 8.0 Hz, 1H), 2.58 (s, 3H), 2.33 (s, 3H). 13C NMR (125 MHz, CDCl3) δ
white solid in 81% yield (31 mg); Melting point: 187-189 oC. 1H NMR 201.7, 161.7, 153.0, 135.6, 134.8, 130.5, 128.7, 123.5, 120.2, 119.0,
(400 MHz, CDCl3) δ 8.24-8.21 (m, 2H), 7.85-7.83 (m, 1H), 7.71-7.67 32.8, 18.7. HRMS (ESI) m/z: [M+H]+ Calcd for C12H11O3 203.0703;
(m, 1H), 7.47-7.45 (m, 1H), 7.40-7.38 (m, 2H), 4.04 (s, 2H), 2.46 (s, Found 203.0700.
3H). 13C NMR (100 MHz, DMSO) δ 171.5, 164.2 (d, J=525.9 Hz), 4-Acetyl-3,6-dimethyl-1H-isochromen-1-one (4b): This compound
145.6 (d, J=111.9 Hz), 137.8, 135.7, 134.8 (q, J=210 Hz), 133.9, 132.8, was purified by column chromatography to afford a white solid in
130.2, 129.2, 129.1 (q, J=173.0 Hz), 127.0 (q, J=6.4 Hz), 125.6, 37.4, 43% yield (9 mg); Melting point: 112-114 oC. 1H NMR (500 MHz,
21.7. HRMS (ESI) m/z: [M+H]+ Calcd for C17H13F3NO4S 384.0512; CDCl3) δ 8.19 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 8.5 Hz, 1H), 7.08 (s, 1H),
Found 384.0504.
2.57 (s, 3H), 2.46 (s, 3H), 2.30 (s, 3H). 13C NMR (125 MHz, CDCl3) δ
7-Methyl-2-tosylisoquinoline-1,3(2H,4H)-dione
(3m):
This 202.0, 161.8, 152.8, 146.8, 134.8, 130.5, 130.0, 123.5, 118.9, 117.8,
compound was purified by column chromatography to afford a 32.9, 22.6, 18.7. HRMS (ESI) m/z: [M+H]+ Calcd for C13H13O3
white solid in 68% yield (22 mg); Melting point: 191-193 oC. 1H NMR 217.0859; Found 217.0854.
(400 MHz, CDCl3) δ 8.23-8.20 (m, 2H), 7.93-7.90 (m, 1H), 7.41-7.36 4-Acetyl-6-methoxy-3-methyl-1H-isochromen-1-one (4c): This
(m, 3H), 7.14-7.12 (m, 1H), 4.07 (s, 2H), 2.44 (s, 3H), 2.38 (s, 3H). 13
C
compound was purified by column chromatography to afford a
o
1
NMR (100 MHz, CDCl3) δ 168.1, 163.0, 145.8, 138.3, 135.8, 135.4, white solid in 84% yield (20 mg); Melting point: 85-87 C. H NMR
130.1, 129.7, 129.6, 129.4, 127.3, 125.4, 39.6, 21.8, 21.0. HRMS (ESI) (500 MHz, CDCl3) δ 8.20 (d, J = 8.5 Hz, 1H), 7.03-7.01 (m, 1H), 6.68
m/z: [M+H]+ Calcd for C17H16NO4S 330.0795; Found 330.0794.
(d, J = 2.0 Hz, 1H), 3.87 (s, 3H), 2.56 (s, 3H), 2.29 (s, 3H). 13C NMR
7-Phenyl-2-tosylisoquinoline-1,3(2H,4H)-dione
(3n):
This (125 MHz, CDCl3) δ 201.8, 165.3, 161.5, 153.8, 136.9, 132.7, 118.8,
compound was purified by column chromatography to afford a 116.3, 113.2, 106.6, 56.1, 32.8, 18.9. HRMS (ESI) m/z: [M+H]+ Calcd
white solid in 65% yield (25 mg); Melting point: 162-164 oC. 1H NMR for C13H13O4 233.0808; Found 233.0800.
(400 MHz, CDCl3) δ 8.36 (d, J = 2.0 Hz, 1H), 8.25-8.22 (m, 2H), 7.84- 4-Acetyl-3-methyl-6-phenyl-1H-isochromen-1-one
(4d):
This
7.81 (m, 1H), 7.59-7.56 (m, 2H), 7.48-7.43 (m, 2H), 7.41-7.37 (m, 3H), compound was purified by column chromatography to afford a
7.33-7.31 (m, 1H), 4.16 (s, 2H), 2.45 (s, 3H). 13C NMR (100 MHz, white solid in 65% yield (18 mg); Melting point: 149-150 oC. 1H NMR
CDCl3) δ 167.8, 162.9, 146.0, 141.4, 138.9, 135.3, 133.3, 131.8, (500 MHz, CDCl3) δ 8.37 (d, J = 8.0 Hz, 1H), 7.75-7.73 (m, 1H), 7.63-
129.7, 129.5, 129.1, 128.3, 127.9, 127.9, 127.0, 126.0, 39.7, 21.8. 7.57 (m, 2H), 7.52-7.42 (m, 4H), 2.61 (s, 3H), 2.35 (s, 3H). 13C NMR
HRMS (ESI) m/z: [M+H]+ Calcd for C22H18NO4S 392.0951; Found (125 MHz, CDCl3) δ 201.7, 161.6, 153.3, 148.5, 139.7, 135.3, 131.0,
392.0955.
129.5, 129.3, 127.9, 127.8, 121.8, 119.1, 118.9, 32.9, 18.8. HRMS
7-Chloro-2-tosylisoquinoline-1,3(2H,4H)-dione
(3o):
This (ESI) m/z: [M+H]+ Calcd for C18H15O3 279.1016; Found 279.1013.
compound was purified by column chromatography to afford a 4-Acetyl-3-methyl-6-(trifluoromethyl)-1H-isochromen-1-one (4e):
o
white solid in 50% yield (17 mg); Melting point:201-203 C. 1H NMR This compound was purified by column chromatography to afford a
o
1
(400 MHz, CDCl3) δ 8.22-8.19 (m, 2H), 8.11-8.10 (m, 1H), 7.57-7.55 white solid in 69% yield (19 mg); Melting point: 99-102 C. H NMR
(m, 1H), 7.40-7.37 (m, 2H), 7.22-7.19 (m, 1H), 4.09 (s, 2H), 2.45 (s, (500 MHz, CDCl3) δ 8.43 (d, J = 8.5 Hz, 1H), 7.76-7.74 (m, 1H), 7.62 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 167.2, 161.7, 146.1, 135.1, 134.8, 1H), 2.61 (s, 3H), 2.39 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 200.6,
134.6, 131.3, 129.7, 129.5, 129.4, 128.8, 127.1, 39.3, 21.8. HRMS 160.5, 155.0, 137.0 (q, J=26.2 Hz), 135.2, 131.5, 125.1 (q, J=3.0 Hz),
(ESI) m/z: [M+H]+ Calcd for C16H13ClNO4S 350.0248; Found 350.0241. 123.5 (d, J=217.3 Hz), 122.7, 120.9 (q, J=3.5 Hz), 118.4, 32.9, 19.1.
6,8-Dimethyl-2-tosylisoquinoline-1,3(2H,4H)-dione
(3p):
This HRMS (ESI) m/z: [M+H]+ Calcd for C13H10F3O3 271.0577; Found
compound was purified by column chromatography to afford a 271.0580.
white solid in 51% yield (18 mg); Melting point: 203-205 oC. 1H NMR
6 | J. Name., 2018, 00, 1-5
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Organic & Biomolecular Chemistry
Journal Name COMMUNICATION
1,1'-(3-Methyl-1-oxo-1H-isochromene-4,6-diyl)bis(ethan-1-one)
121.6, 118.4, 32.8, 18.9. HRMS (ESI) m/z: [M+H]+ Calcd for
View Article Online
DOI: 10.1039/C9OB01789E
(4f): This compound was purified by column chromatography to C12H10ClO3 237.0313; Found 237.0309.
afford a white solid in 51% yield (12 mg); Melting point: 116-117 oC. 4-Acetyl-7-bromo-3-methyl-1H-isochromen-1-one
(4m):
This
1H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 8.0 Hz, 1H), 8.05-8.02 (m, compound was purified by column chromatography to afford a
1H), 7.91 (d, J = 1.2 Hz, 1H), 2.68 (s, 3H), 2.63 (s, 3H), 2.37 (s, 3H). white solid in 69% yield (19 mg); Melting point: 122-124 oC. 1H NMR
13C NMR (100 MHz, CDCl3) δ 200.6, 196.9, 160.5, 153.9, 141.9, 134.7, (500 MHz, CDCl3) δ 8.43 (s, 1H), 7.83-7.81 (m, 1H), 7.24 (d, J=8.5 Hz,
130.7, 127.3, 123.1, 122.7, 118.4, 32.6, 27.0, 18.6. HRMS (ESI) m/z: 1H), 2.57 (s, 3H), 2.33 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 200.9,
[M+H]+ Calcd for C14H13O4 245.0808; Found 245.0811.
Methyl
160.3, 153.8, 138.6, 133.5, 133.0, 125.3, 122.4, 121.7, 118.4, 32.8,
4-acetyl-3-methyl-1-oxo-1H-isochromene-6-carboxylate 18.9. HRMS (ESI) m/z: [M+H]+ Calcd for C12H10BrO3 280.9808; Found
(4g): This compound was purified by column chromatography to 280.9804.
afford a white solid in 84% yield (22 mg); Melting point: 147-149 oC. 8-Acetyl-7-methyl-5H-[1,3]dioxolo[4,5-g]isochromen-5-one (4n):
1H NMR (500 MHz, CDCl3) δ 8.37 (d, J = 8.0 Hz, 1H), 8.14-8.12 (m, This compound was purified by column chromatography to afford a
1H), 8.00 (s, 1H), 3.98 (s, 3H), 2.62 (s, 3H), 2.35 (s, 3H). 13C NMR white solid in 60% yield (15 mg); Melting point: 144-146 oC. 1H NMR
(125 MHz, CDCl3) δ 201.0, 165.9, 160.9, 154.0, 136.4, 134.8, 130.8, (400 MHz, CDCl3) δ 7.97 (d, J = 8.4 Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H),
129.0, 125.0, 123.2, 118.8, 53.2, 32.9, 18.8. HRMS (ESI) m/z: [M+H]+ 6.13 (s, 2H), 2.51 (s, 3H), 2.23 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
Calcd for C14H13O5 261.0757; Found 261.0758.
4-Acetyl-6-fluoro-3-methyl-1H-isochromen-1-one
201.2, 160.6, 152.8, 151.7, 140.2, 126.7, 117.3, 114.7, 114.1, 109.6,
(4h):
This 102.7, 32.3, 17.5. HRMS (ESI) m/z: [M+H]+ Calcd for C13H11O5
compound was purified by column chromatography to afford a 247.0601; Found 247.0600.
o
1
white solid in 79% yield (17 mg);1H Melting point: 110-112 C. H 4-Acetyl-3-methyl-1H-benzo[g]isochromen-1-one
(4o):
This
NMR (500 MHz, CDCl3) δ 8.35-8.32 (m, 1H), 7.22-7.20 (m, 1H), 7.05- compound was purified by column chromatography to afford a
7.02 (m, 1H), 2.58 (s, 3H), 2.35 (s, 3H). 13C NMR (125 MHz, CDCl3) δ white solid in 92% yield (23 mg); Melting point: 141-143 oC. 1H NMR
200.8, 167.2 (d, J=204.5 Hz), 160.7, 154.9, 137.4 (d, J=8.6 Hz), 133.8 (500 MHz, CDCl3) δ 8.95 (s, 1H), 8.03 (d, J = 8.0 Hz, 1H), 7.90 (d, J =
(d, J=8.3 Hz), 118.4 (d, J=2.2 Hz), 117.0 (d, J=18.4 Hz), 116.7, 110.0 8.0 Hz, 1H), 7.72 (s, 1H), 7.68-7.65 (m, 1H), 7.60-7.57 (m, 1H), 2.66
(d, J=19.3 Hz), 32.8, 19.1. HRMS (ESI) m/z: [M+H]+ Calcd for (s, 3H), 2.34 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 201.8, 161.6, 150.7,
C12H10FO3 221.0608; Found 221.0609.
4-Acetyl-6-chloro-3-methyl-1H-isochromen-1-one
136.4, 132.6, 132.1, 129.8, 129.6, 129.1, 128.1, 127.2, 121.8, 118.5,
(4i):
This 118.1, 32.5, 18.3. HRMS (ESI) m/z: [M+H]+ Calcd for C16H13O3
compound was purified by column chromatography to afford a 253.0859; Found 253.0858.
white solid in 82% yield (19 mg); Melting point: 118-120 oC. 1H NMR 4-(2-Oxopropyl)-N-tosylfuran-3-carboxamide (4p): This compound
(500 MHz, CDCl3) δ 8.24 (d, J = 8.5 Hz, 1H), 7.49-7.47 (m, 1H), 7.34 was purified by column chromatography to afford a white solid in
(d, J = 2.0 Hz, 1H), 2.59 (s, 3H), 2.35 (s, 3H). 13C NMR (125 MHz, 53% yield (17 mg); Melting point: 175-177 C. H NMR (500 MHz,
CDCl3) δ 200.8, 160.9, 154.7, 142.5, 136.1, 132.0, 129.2, 123.4, DMSO) δ 12.17 (s, 1H), 7.90 (d, J = 8.0 Hz, 2H), 7.72 (d, J = 2.0 Hz,
118.5, 118.1, 32.8, 19.0. HRMS (ESI) m/z: [M+H]+ Calcd for 1H), 7.49 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 2.0 Hz, 1H), 4.13 (s, 2H), 2.45
o
1
C12H10ClO3 237.0313; Found 237.0309.
(s, 3H), 2.15 (s, 3H). 13C NMR (125 MHz, DMSO) δ 203.5, 162.0,
4-Acetyl-6-bromo-3-methyl-1H-isochromen-1-one
(4j):
This 157.5, 145.1, 143.2, 137.5, 130.4, 128.5, 116.3, 110.1, 42.9, 30.5,
compound was purified by column chromatography to afford a 21.9. HRMS (ESI) m/z: [M+H]+ Calcd for C15H16NO5S 322.0744;
white solid in 74% yield (21 mg); Melting point: 131-133 oC. 1H NMR Found 322.0743.
(500 MHz, CDCl3) δ 8.15 (d, J = 8.5 Hz, 1H), 7.65-7.63 (m, 1H), 7.51 Dimethyl (3-methyl-1-oxo-1H-isochromen-4-yl)phosphonate (4t):
(d, J = 1.5 Hz, 1H), 2.59 (s, 3H), 2.35 (s, 3H). 13C NMR (125 MHz, This compound was purified by column chromatography to afford a
o
1
CDCl3) δ 200.8, 161.0, 154.7, 136.2, 132.1, 132.0, 131.3, 126.5, white solid in 67% yield (18 mg); Melting point: 70-71 C. H NMR
118.9, 118.0, 32.8, 19.0. HRMS (ESI) m/z: [M+H]+ Calcd for (500 MHz, CDCl3) δ 8.32-8.30 (m, 1H), 8.13 (d, J = 8.0 Hz, 1H), 7.77-
C12H10BrO3 280.9808; Found 280.9801.
4-Acetyl-7-fluoro-3-methyl-1H-isochromen-1-one
7.73 (m, 1H), 7.56-7.50 (m, 1H), 3.81 (s, 3H), 3.79 (s, 3H), 2.77 (d, J =
(4k):
This 2.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 166.0, 165.8, 161.0, 135.6,
compound was purified by column chromatography to afford a 135.5, 135.1, 129.6, 128.2, 125.9, 119.8, 119.7, 102.4, 100.8, 52.6,
white solid in 48% yield (11 mg); Melting point: 138-141 oC. 1H NMR 52.5, 20.6. HRMS (ESI) m/z: [M+H]+ Calcd for C12H14O5P 269.0573;
(500 MHz, CDCl3) δ 8.15 - 8.13 (m, 1H), 7.54-7.42 (m, 2H), 2.51 (d, J Found 269.0570.
= 3.5 Hz, 3H), 2.26 (s, 3H). 13C NMR (100 MHz, CDCl3) δ200.7, 160.2, Diethyl (3-methyl-1-oxo-1H-isochromen-4-yl)phosphonate (4u):
155.9 (d, J=249.8 Hz), 152.1, 129.3 (d, J=8.0 Hz), 126.2 (d, J=3.6 Hz), This compound was purified by column chromatography to afford a
o
1
123.7 (d, J=12.6 Hz), 121.7 (d, J=3.9 Hz), 121.6 (d, J=21.0 Hz), 114.5, white solid in 95% yield (28 mg); Melting point: 62-64 C. H NMR
31.8 (d, J=9.2 Hz), 17.6. HRMS (ESI) m/z: [M+H]+ Calcd for C12H10FO3 (400 MHz, CDCl3) δ 8.32-8.29 (m, 1H), 8.22-8.20 (m, 1H), 7.77-7.73
221.0608; Found 221.0604.
4-Acetyl-7-chloro-3-methyl-1H-isochromen-1-one
(m, 1H), 7.54-7.50 (m, 1H), 4.28-4.18 (m, 2H), 4.15-4.05 (m, 2H),
(4l):
This 2.77 (d, J = 2.4 Hz, 3H), 1.35-1.31 (m, 6H). 13C NMR (100 MHz, CDCl3)
compound was purified by column chromatography to afford a δ 165.5, 165.2, 161.2, 135.8, 135.7, 134.9, 129.5, 128.1, 126.2,
white solid in 62% yield (15 mg); Melting point: 124-126 oC. 1H NMR 119.9, 119.7, 103.7, 101.8, 62.3, 62.3, 20.6, 16.3, 16.3. HRMS (ESI)
(500 MHz, CDCl3) δ 8.28 (d, J = 1.0 Hz, 1H), 7.69-7.66 (m, 1H), 7.31 m/z: [M+H]+ Calcd for C14H18O5P 297.0886; Found 297.0890.
(d, J = 8.5 Hz, 1H), 2.57 (s, 3H), 2.34 (s, 3H). 13C NMR (125 MHz, 3,4-Dihydro-1H-benzo[c]chromene-1,6(2H)-dione
(4v):
This
CDCl3) δ 201.0, 160.5, 153.6, 135.8, 134.7, 133.2, 129.9, 125.2, compound was purified by column chromatography to afford a
white solid in 96% yield (21 mg); Melting point: 153-155 oC. 1H NMR
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(500 MHz, CDCl3) δ 9.05 (d, J = 8.5 Hz, 1H), 8.29- 8.27 (m, 1H), 7.83- 129.3, 128.2, 127.5, 126.2, 123.9, 120.1, 119.1, 39.7, 39.6, 21.5.
View Article Online
+
DOI: 10.1039/C9OB01789E
7.75 (m, 1H), 7.57-7.49 (m, 1H), 2.96-2.93 (m, 2H), 2.68-2.65 (m, 2H), HRMS (APCI) m/z: [M+H] Calcd for C23H20N2O6S2 485.0836; Found
2.21-2.15 (m, 2H). 13C NMR (125 MHz, CDCl3) δ 197.3, 169.9, 160.9, 485.0842.
136.0, 134.4, 130.0, 128.8, 126.4, 120.3, 112.0, 39.3, 29.4, 20.4.
HRMS (ESI) m/z: [M+H]+ Calcd for C13H11O3 215.0703; Found Conflicts of interest
215.0700.
There are no conflicts to declare.
3-Methyl-4-phenyl-1H-isochromen-1-one (4w): This compound
was purified by column chromatography to afford a white solid in
Acknowledgements
86% yield (20 mg); Melting point: 127-129 oC. 1H NMR (400 MHz,
CDCl3) δ 8.35-8.32 (m, 1H), 7.61-7.59 (m, 1H), 7.52-7.43 (m, 4H),
We gratefully acknowledge the National Natural Science
7.29-7.26 (m, 3H), 7.01-6.99 (m, 1H), 2.13 (s, 3H). 13C NMR (100 Foundation of China (21772001), and the Start-up Research Fund of
MHz, CDCl3) δ 162.7, 151.6, 138.7, 134.6, 134.5, 130.6, 129.5, 129.0, Anhui Normal University for their financial support.
128.2, 127.4, 124.5, 120.0, 116.4, 18.1. HRMS (ESI) m/z: [M+H]+
Notes and references
Calcd for C16H13O2 237.0910; Found 237.0906.
4-(4-Chlorophenyl)-3-methyl-1H-isochromen-1-one
(4x):
This
1
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compound was purified by column chromatography to afford a
white solid in 60% yield (16 mg); Melting point: 154-157 oC. 1H NMR
(400 MHz, CDCl3) δ 8.35-8.32 (m, 1H), 7.63-7.57 (m, 1H), 7.50-7.44
(m, 3H), 7.25-7.21 (m, 2H), 6.97 (d, J = 8.0 Hz, 1H), 2.13 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 162.5, 151.8, 138.3, 134.8, 134.3, 132.9,
132.0, 129.6, 129.3, 127.6, 124.3, 120.0, 115.3, 18.1. HRMS (ESI)
m/z: [M+H]+ Calcd for C16H12ClO2 271.0517; Found 271.0520.
Methyl 4-(3-methyl-1-oxo-1H-isochromen-4-yl)benzoate (4y): This
compound was purified by column chromatography to afford a
white solid in 65% yield (19 mg); Melting point: 152-155 oC. 1H NMR
(400 MHz, CDCl3) δ 8.36-8.34 (m, 1H), 8.21-8.15 (m, 2H), 7.63-7.57
(m, 1H), 7.51-7.45 (m, 1H), 7.41-7.35 (m, 2H), 6.94 (d, J = 8.0 Hz, 1H),
3.98 (s, 3H), 2.13 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 166.7, 162.4,
151.7, 139.4, 138.0, 134.8, 130.8, 130.3, 130.1, 129.7, 127.7, 124.2,
120.0, 115.6, 52.4, 18.1. HRMS (ESI) m/z: [M+H]+ Calcd for C18H15O4
295.0965; Found 295.0964.
4-(4-Fluorophenyl)-3-methyl-1H-isochromen-1-one
compound was purified by column chromatography to afford a
(4z):
This
o
1
white solid in 25% yield (6 mg); Melting point: 135-137 C. H NMR
(400 MHz, CDCl3) δ 8.35-8.33 (m, 1H), 7.65-7.56 (m, 1H), 7.53-7.44
(m, 1H), 7.29-7.17 (m, 6H), 6.97 (d, J = 8.0 Hz, 1H), 2.13 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 162.6 (d, J=246.3 Hz), 162.5, 151.9, 138.6,
134.7, 132.3 (d, J=8.0 Hz), 130.3, 129.6, 127.5, 124.3, 120.0, 116.1
(d, J=21.5 Hz), 115.4, 18.1. HRMS (ESI) m/z: [M+H]+ Calcd for
C16H12FO2 255.0816; Found 255.0821.
3'-(methylsulfonamido)-N-tosyl-[1,1'-biphenyl]-3-carboxamide (8):
This compound was purified by column chromatography to afford a
white solid in 90% yield; Melting point: 186-188 oC. 1H NMR (400
MHz, DMSO-d6) δ 12.64 (s, 1H), 9.85 (s, 1H), 8.13 (s, 1H), 7.93-7.84
(m, 4H), 7.62-7.58 (m, 1H), 7.52-7.45 (m, 5H), 7.29-7.26 (m, 1H),
3.04 (s, 3H), 2.41 (s, 3H). 13C NMR (100 MHz, DMSO) δ 165.7, 144.8,
140.7, 140.5, 139.6, 137.1, 132.8, 131.8, 130.5, 130.0, 130.0, 128.3,
128.2, 127.0, 123.1, 119.9, 118.8, 39.8, 21.6. HRMS (APCI) m/z:
[M+H]+ Calcd for C21H20N2O5S2 445.0886; Found 445.0891.
2
3
4
5
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1
Melting point: 219-221 oC. H NMR (400 MHz, Methylene Chloride-
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8 | J. Name., 2018, 00, 1-5
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