Cu-Catalyzed Cascade Annulation of Alkynols with 2-Azidobenzaldehydes: Access to 6H-Isochromeno[4,3-c]quinoline

Article abstract of DOI:10.1021/acs.joc.7b00937

A copper-catalyzed cascade reaction of alkynols and 2-azidobenzaldehydes has been achieved, giving 6H-isochromeno[4,3-c]quinoline in yields of 40-81%. This reaction provides a novel, concise strategy for rapidly constructing compounds with fused N- and O-containing heterocycles. In contrast to previously reported reactions of alkynols in which the first step is intramolecular cycloisomerization, the first step in this novel reaction of alkynols is entropically unfavorable intermolecular addition. The resulting hemiacetal intermediate then undergoes intramolecular cyclization and aromatization to afford the product.

Full text of DOI:10.1021/acs.joc.7b00937

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Note
Cu-Catalyzed Cascade Annulation of Alkynols with 2-
Azidobenzaldehydes: Access to 6H-Isochromeno[4,3-c]quinoline
Xiao-Feng Mao, Xiao-Ping Zhu, Deng-Yuan Li, and Pei-Nian Liu
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 29 May 2017
Downloaded from http://pubs.acs.org on May 30, 2017
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Cu-Catalyzed Cascade Annulation of Alkynols with
2-Azidobenzaldehydes: Access to
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6H-Isochromeno[4,3-c]quinoline
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XiaoꢀFeng Mao, XiaoꢀPing Zhu, DengꢀYuan Li and PeiꢀNian Liu*
Shanghai Key Laboratory of Functional Materials Chemistry, Key Lab for Advanced Materials
and School of Chemistry & Molecular Engineering, East China University of Science and
Technology, Meilong Road 130, Shanghai 200237, China
Fax: (+86)ꢀ21ꢀ64250552, Eꢀmail: liupn@ecust.edu.cn
Abstract: A copperꢀcatalyzed cascade reaction of alkynols and 2ꢀazidobenzaldehydes
has been achieved, giving 6Hꢀisochromeno[4,3ꢀc]quinoline in yields of 40 to 81%.
This reaction provides a novel, concise strategy for rapidly constructing compounds
with fused Nꢀ and Oꢀcontaining heterocycles. In contrast to previously reported
reactions of alkynols in which the first step is intramolecular cycloisomerization, the
first step in this novel reaction of alkynols is entropically unfavorable intermolecular
addition. The resulting hemiacetal intermediate then undergoes intramolecular
cyclization and aromatization to afford the product.
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Quinoline alkaloids have attracted extensive attention due to their useful
biological activities and interesting properties.1 Of particular interest are
pyrano[3,2ꢀc]quinoline derivatives, which are present in several biologically active
molecules.2 For example, 5ꢀphenylꢀpyrano[3,2ꢀc]quinolineꢀ6ꢀchlorotacrine hybrid I
can inhibit acetylcholinesterase (AChE) as well as butyrylcholinesterase (BChE).2e
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Molecule II, extracted from
a
strain of Chaetomium funicola, inhibits
metalloꢀβꢀlactamases.2f Distomadine III, isolated from the New Zealand ascidian
Pseudodistoma aureum, exhibits mild antifungal activity (Fig. 1).2g
Figure 1. Biologically active molecules containing a pyrano[3,2ꢀc]quinoline motif.
Several groups have made extensive efforts to synthesize pyrano[3,2ꢀc]quinoline
derivatives efficiently, and most of the syntheses reported so far require multiple steps
because of the difficulty in simultaneously constructing pyridine and pyran rings.
Recently, Flynn and coꢀworkers generated these compounds via I2ꢀcatalyzed
cyclization of Nꢀ(oꢀalkynolphenyl)imines.3 Wang and coꢀworkers generated them via
thermolysis of 1ꢀisocyanatoꢀ2ꢀ(5ꢀmethoxypentꢀ1ꢀynꢀ1ꢀyl)benzene, but this method
requires harsh conditions and gives only low yield (9%).4a Therefore, more concise
and efficient synthetic routes to pyrano[3,2ꢀc]quinoline derivatives are needed.
One approach to developing such syntheses may lie in transition metalꢀcatalyzed
cascade transformation of alkynols. Such transformations are useful for constructing
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Oꢀcontaining heterocyclic compounds, including natural products and drugs.5ꢀ13 Most
of these reactions are catalyzed by tungsten,6 gold,7 platinum,8 palladium,9 and copper
catalysts.10 The typical approach is to subject alkynols to intramolecular
cycloisomerization in order to yield highly reactive endoꢀ or exoꢀcyclic enol ether
intermediates. These intermediates subsequently undergo diverse transformations
such as Prinsꢀtype cyclization11, DielsꢀAlder reaction,12 and Povarov reaction.13 Since
this approach usually involves addition to a C=C bond of endoꢀ or exoꢀcyclic enol
ethers, the resulting derivatives are limited to those having endoꢀ or exoꢀcyclic enol
ethers as the basic skeleton (Scheme 1a).14 It is possible that other types of
intermediates and therefore products can be generated by subjecting alkynols to
intermolecular reactions with other types of reactants. However, intermolecular
addition of alkynols is entropically unfavorable, making this approach challenging.
Scheme 1. Cascade reactions of alkynols
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Here we report a copperꢀcatalyzed cascade annulation of alkynols with
2ꢀazidobenzaldehydes, in which the first step is the entropically unfavorable
intermolecular addition of a hydroxyl group to the aldehyde group. This
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unprecedented reaction provides
a
concise method for constructing the
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6Hꢀisochromeno[4,3ꢀc]quinoline skeleton in moderate to good yields. The reaction
combines intermolecular addition, intramolecular cyclization and aromatization in a
single operation (Scheme 1b). This new strategy avoids intramolecular
cycloisomerization of internal alkynols and connects two substrates in the first step to
promote subsequent tandem annulation.
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As shown in Table 1, our study started with the Cu(OTf)2ꢀmediated reaction of
o
internal alkynol 1a with 2ꢀazidobenzaldehyde 2a at 80 C in acetonitrile. Using 0.2
equiv of Cu(OTf)2 gave the corresponding product 3a in 10% isolated yield (entry 1).
Then we screened various reaction conditions to optimize the catalytic process. The
solvents toluene, DMF, and THF were ineffective for this reaction (entries 2ꢀ4).
Screening of additives showed that K2S2O8 substantially improved yield from 10% to
59% (entry 5). Lowering catalyst load to 0.1 equiv or increasing the dosage of K2S2O8
to 2 equiv was ineffective (entries 6 and 7). Reversing the ratio of 1a : 2a to 1.2 : 1
made the reaction more efficient, affording product in 74% yield (entry 8), which was
o
increased to 81% by raising the temperature to 120 C (entry 9). Decreasing additive
loading to 20 mol% reduced the yield from 81% to 40% (entry 10). The catalysts
Sc(OTf)3, AgOTf, and In(OTf)3 gave product 3a in yields of 55ꢀ62% (entries 11ꢀ13).
No product was detected using Cu(OAc)2, demonstrating the importance of the
trifluoromethanesulfonic anion in the reaction (entry 14). Other oxidizing agents did
not deliver better results than K2S2O8 (entries 15ꢀ17).
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Table 1. Optimization of reaction conditions.a
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temp yield
entry catalyst
additive
solvent
MeCN
(oC)
(%)b
1
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
ꢀ
ꢀ
ꢀ
ꢀ
80
10
0
2
Toluene 80
3
DMF
80
0
4
THF
80
0
5
Cu(OTf)2 K2S2O8
Cu(OTf)2 K2S2O8
Cu(OTf)2 K2S2O8
Cu(OTf)2 K2S2O8
Cu(OTf)2 K2S2O8
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
80
59
40
47
74
81
40
60
55
62
0
6c
7d
8e
9e
80
80
80
120
120
120
120
120
120
120
120
120
120
120
10e,f Cu(OTf)2 K2S2O8
11e
12e
13e
14e
15e
16e
17e
18e
19e
Sc(OTf)3
AgOTf
K2S2O8
K2S2O8
K2S2O8
In(OTf)3
Cu(OAc)2 K2S2O8
Cu(OTf)2 (NH4)2S2O8 MeCN
64
trace
0
Cu(OTf)2 DDQ
Cu(OTf)2 Cu(OAc)2
Cu(OTf)2 BQ
MeCN
MeCN
MeCN
MeCN
trace
21
Cu(OTf)2 tꢀBuOOH
aReactions were performed in sealed tubes containing 1a (0.2 mmol), 2a (0.24 mmol),
catalyst (0.04 mmol), additive (0.2 mmol), and solvent (2 mL) under Ar, unless noted
otherwise. bIsolated yield. cK2S2O8 (0.4 mmol) was used. dCu(OTf)2 (0.02 mmol) was
used. e1a (0.24 mmol) and 2a (0.2 mmol) were used. fK2S2O8 (0.04 mmol) was used.
Using the optimized conditions for this cascade reaction, we evaluated the
substrate scope. First we examined the ability of various substituted alkynols 1 to
react with 2ꢀazidobenzaldehyde (Scheme 2). A substrate carrying a methoxyl group at
the R1 position reacted smoothly, generating 3b in 80% yield. Placing Me and F at the
R1 position hampered the reaction slightly, generating 3c in 60% yield and 3d in 63%
yield. Placing the electronꢀwithdrawing group CF3 at the same position efficiently
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generated product 3e in 75% yield. Internal alkynols bearing F and Cl at the R2
position also participated in the reaction, generating product 3f in 70% yield and 3g in
60% yield. The structure of product 3g was confirmed by singleꢀcrystal Xꢀray
diffraction analysis (see Supporting Information). A substrate with Me at the R3
position gave the product 3h in 57% yield.
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Scheme 2. Scope of Alkynols 1a
aReactions were conducted at 120 oC for 6ꢀ12 h using 1 (0.24 mmol), 2a (0.2 mmol),
Cu(OTf)2 (0.04 mmol), K2S2O8 (0.2 mmol), and acetonitrile (2 mL). Isolated yields
are shown.
The reaction also proceeded with (2ꢀ(phenylethynyl)phenyl)methanol, giving 3i
in 40% yield. These results illustrate the importance of an electronꢀdonating group at
the R4 position. Using (2ꢀ(pꢀtolylethynyl)phenyl)methanol led to 3j in 58% yield;
4ꢀpentylphenyl alkynols also reacted, though the corresponding product 3k was
generated in only 43% yield. The substrates 4ꢀ(tertꢀbutyl) and 4ꢀoctyloxy alkynols
generated 3l in 51% yield and 3m in 66% yield. An alkynol containing the
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heterocyclic thiophenyl group afforded 3n in 59% yield. Note that alkynol substituted
with alkyl group such as (2ꢀ(hexꢀ1ꢀynꢀ1ꢀyl)phenyl)methanol (R4 = butyl) did not
reacted with 2a under standard conditions.
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Scheme 3. Scope of 2-Azidobenzaldehyde 2a
o
aReactions were conducted at 120 C for 3ꢀ6 h using 1a (0.24 mmol), 2 (0.2 mmol),
Cu(OTf)2 (0.04 mmol), K2S2O8 (0.2 mmol), and acetonitrile (2 mL). Isolated yields
are shown.
To explore the full scope of the reaction, we examined the ability of
2ꢀazidobenzaldehyde to react with internal alkynol 1 (Scheme 3). The substrate
2ꢀazidobenzaldehyde with Cl groups at the R5, R6 or R7 position afforded products
3o-3q in 47ꢀ72% yields. Substrates carrying Br at the R6 position generated 3r in 55%
yield. Placing the electronꢀwithdrawing groups CF3 or methyl ester at the same
position provided 3s in 57% yield and 3t in 55% yield. Placing the electronꢀdonating
groups OMe or Me at the R7 position afforded 3u in 60% yield and 3v in 74% yield.
We performed some experiments to clarify the mechanism of this cascade reaction
(Scheme 4). Firstly, the reaction of 4 and 2a was carried out but no reaction proceeded
(eq 1), which expelled the possibility of the rearrangement of 2a to imino ketene and
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the following formal [4+2] cycloaddition to form the product 5. The standard reaction
of 1a and 2a in the presence of 1 equiv. of 2,4,6ꢀtriꢀtertꢀbutylphenol produced 3a in 62%
yield, which expelled the possibility of radical process for this reaction.
Scheme 4. Mechanistic Investigations
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Next, we reacted 1a under standard conditions and obtained the cycloisomerization
product 6 only in 8% yield, whereas we observed no product when we reacted 2a with
the endoꢀcyclic enol ether 6 under the same conditions (eq 2). This demonstrates that
the reaction proceeds via intermolecular alkynol cyclization, rather than
intramolecular cycloisomerization. Moreover, the control reaction of 1a and 2a under
standard reaction conditions without K2S2O8 only gave 3a in 18% yield (eq 3),
indicating that Cu(OTf)2 was not the active catalyst for this reaction. Similarly, the
Lewis acid AlCl3 and Brønsted acid HOTf were also tested as the catalysts in this
reaction, 15% and 20% yields were obtained respectively, illustrating conventional
acids can promote this reaction although not so effecitive. Lewis acid ZnCl2 (20 mol%)
was also tested with 1 equiv. K2S2O8 and the product 3a was obtained in 30% yield.
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Figure 2. Line a: Cu(OTf)2 (0.02 mmol) in MeCN at 120 oC for 1 h. Line b: Cu(OTf)2
o
(0.02 mmol) and K2S2O8 (0.1 mmol) in MeCN at 120 C for 1 h. Line c: 1a (0.12
o
mmol) and 2a (0.1 mmol) was reacted at 120 C for 1 h with Cu(OTf)2 (0.02 mmol)
and K2S2O8 (0.1 mmol) in MeCN.
To clarify the active catalyst and the role of K2S2O8 in the cascade reaction
(Figure 2), we explored control experiments monitored by electron paramagnetic
o
resonance (EPR). When Cu(OTf)2 was stirred in MeCN at 120 C for 1 h, the EPR
signal of Cu(II) could be clearly seen (Fig. 2, line a). However, when the mixture of
Cu(OTf)2 and excess K2S2O8 was stirred at the same condition, the signal of Cu(II)
disappeared, suggesting that Cu(II) species was oxidized to Cu(III) (Fig. 2, line b).
Next, under standard conditions to form 3a, an EPR spectra line c similar to line b
was obtained, indicating that Cu(III) species may be the active catalyst for this
cascade reaction (Fig. 2, line c).
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Scheme 5. Proposed Mechanism
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On the basis of these mechanistic studies, we propose a tentative mechanism for
this copperꢀpromoted cascade reaction of internal alkynol and 2ꢀazidobenzaldehyde to
generate 6Hꢀisochromeno[4,3ꢀc]quinoline (Scheme 5). Firstly, with the oxidization of
K2S2O8, Cu(II) was transformed into Cu(III). Then coordination between the carbonyl
of 2a and Cu(III) (A) enhances electrophilicity of the aldehyde. Next the hydroxyl
group adds to the electroꢀdeficient aldehyde, producing unstable intermediate B.
Acidic conditions convert B into C, and subsequent intramolecular cyclization of C
generates intermediate D, which undergoes aromatization to form the product 3a.
In summary, we have developed a new copperꢀcatalyzed cascade annulation of
alkynol and 2ꢀazidobenzaldehyde to give 6Hꢀisochromeno[4,3ꢀc]quinoline in
moderate to good yields. The first step in this novel approach is entropically
unfavorable intermolecular addition, instead of conventional intramolecular
cycloisomerization. The resulting hemiacetal intermediate undergoes intramolecular
cyclization and aromatization to afford the product. This new strategy may allow the
development of new cascade reactions involving alkynols, as well as the
straightforward construction of highly diverse heterocyclic skeletons.
Experimental Section
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All manipulations were carried out under a nitrogen or argon atmosphere using
standard Schlenk techniques, unless otherwise stated. Solvents were distilled under
nitrogen from sodiumꢀbenzophenone (THF, toluene, dioxane) or calcium hydride
(MeCN, CH3NO2, DMF, DCE). Other chemicals were obtained from commercial
sources, and were used without further purification. The alkynols[15] and
s2ꢀazidobenzaldehydes[16] were prepared according to the literature methods.
Chemical shifts (δ, ppm) in the 1H NMR spectra were recorded using TMS as internal
standard. Chemical shifts in 13C{1H} NMR spectra were internally referenced to
CDCl3 (δ = 77.16 ppm). EPR spectra were recorded on a Bruker BioSpin GmbH
spectrometer. The sample was taken out into a thin small tube and then detected by
EPR spectrometer at indicated temperature and parameters.
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General procedure for the ERP analysis.
After 1 h, the solution sample was taken out into a small tube and then analyzed
by EPR. EPR spectra was recorded at room temperature on EPR spectrometer
operated at 9.870 GHz. Typical spectrometer parameters are shown as follows, sweep
width: 3000G; center field sets: 3500G; time constant: 163.84 ms; sweep time: 41.943
s; modulation amplitude: 4.0 G; modulation frequency: 100 kHz; receiver gain: 7.1 x
104; microwave power: 2.016 mW.
Typical Experimental Procedure for 3 (3a as an example).
To a mixture of internal alkynol 1a (57.12 mg, 0.24 mmol) and
2ꢀazidobenzaldehyde 2a (29.4 mg, 0.2 mmol) in CH3CN (2 mL) was added the
copper(II) trifluoromethanesulfonate (14.4 mg, 0.04mmol), K2S2O8 (54 mg, 0.2 mmol)
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under Ar. The reaction mixture was stirred at 120 oC for 6 hours and the progress was
monitored using TLC detection. After completion of present reaction, the solvent was
extracted with ethyl acetate. The combined organic layers were washed with H2O,
NH4Cl and brine, dried over MgSO4, filtrated, and evaporated. After that the crude
product was passed through flash column chromatography on silica gel to afford the
desired products 3a.
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11ꢀ(4ꢀMethoxyphenyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline (3a). The compound was
prepared
from
(2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)methanol
and
2ꢀazidobenzaldehyde following the general procedure. The product 3a was obtained
in 81% yield (55 mg) as a yellow foam after column chromatography (eluent =
petroleum ether/ethyl acetate 10:1 v/v); 1H NMR (400 MHz, CDCl3, 25 oC):
= 8.28 Hz, 1H), 7.98 (d, = 8.40 Hz, 1H), 7.58ꢀ7.62 (m, 3H), 7.38ꢀ7.41 (m, 1H),
7.09ꢀ7.17 (m, 2H), 6.94ꢀ6.98 (m, 1H), 6.88 (d, =8.76 Hz, 2H), 6.84 (d, =7.92 Hz,
1H), 5.24 (s, 2H), 3.78 (s, 3H); 13C NMR (100.6 MHz, CDCl3, 25 oC):
160.3, 159.3,
δ 8.10 (d,
J
J
J
J
δ
157.6, 148.0, 134.0, 131.1, 130.5, 130.4, 129.6, 129.1, 128.0, 127.1, 126.5, 125.8,
+
124.9, 121.9, 119.4, 114.2, 112.9, 69.8, 55.5; HRMS (EI, TOF): caled for C24H19NO3
[M]+: 369.1365, found: 369.1366.
8ꢀMethoxyꢀ11ꢀ(4ꢀmethoxyphenyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline (3b). The
compound
was
prepared
from
(5ꢀmethoxyꢀ2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)methanol and 2ꢀazidobenzaldehyde
following the general procedure. The product 3b was obtained in 80% yield (59 mg)
as a yellow foam after column chromatography (eluent = petroleum ether/ethyl
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8
9
acetate 5:1 v/v); 1H NMR (400 MHz, CDCl3, 25 oC):
(d, = 8.44 Hz, 1H), 7.64ꢀ7.67 (m, 3H), 7.46 (t, = 7.88 Hz, 1H), 6.96 (d,
Hz, 2H), 6.82 (d, =8.76 Hz, 1H), 6.76 (d, =2.56 Hz, 1H), 6.59 (dd, 1 =8.76 Hz, J2
δ
8.16 (d,
J
= 8.24 Hz, 1H), 8.04
J
J
J
= 8.64
J
J
J
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
=2.60 Hz, 1H), 5.28 (s, 2H), 3.87 (s, 3H), 3.79 (s, 3H); 13C NMR (100.6 MHz, CDCl3,
o
25 C):
δ 160.2, 158.8, 158.2, 157.1, 147.5, 134.0, 132.2, 130.9, 129.8, 128.9, 127.9,
125.7, 122.0, 121.6, 119.4, 114.1, 113.4, 112.9, 110.4, 69.7, 55.4, 55.3; HRMS (EI,
TOF): caled for C24H19NO3 [M]+: 369.1365, found: 369.1366.
+
11ꢀ(4ꢀMethoxyphenyl)ꢀ8ꢀmethylꢀ6Hꢀisochromeno[4,3ꢀc]quinoline
compound was prepared
(3c).
The
from
(2ꢀ((4ꢀmethoxyphenyl)ethynyl)ꢀ5ꢀmethylphenyl)methanol and 2ꢀazidobenzaldehyde
following the general procedure. The product 3c was obtained in 60% yield (42 mg)
as a yellow foam after column chromatography (eluent = petroleum ether/ethyl
1
o
acetate 10:1 v/v); H NMR (400 MHz, CDCl3, 25 C):
0.80 Hz, 1H), 8.04 (d, = 8.36 Hz, 1H), 7.64ꢀ7.69 (m, 3H), 7.45ꢀ7.49 (m, 1H), 7.04
(s,, 1H), 6.96 (d, =8.72 Hz, 2H), 6.86 (d, =8.12 Hz, 1H), 6.79 (d, =8.12 Hz, 1H),
5.29 (s, 2H), 3.87 (s, 3H), 2.34 (s, 3H); 13C NMR (100.6 MHz, CDCl3, 25 oC):
160.2,
δ 8.17 (dd, J1 = 8.28 Hz, J2 =
J
J
J
J
δ
158.9, 157.4, 147.8, 137.0, 134.1, 131.0, 130.5, 130.0, 128.9, 128.7, 126.7, 126.4,
125.7, 125.5, 121.7, 119.4, 114.1, 112.9, 69.5, 55.4, 21.1; HRMS (EI, TOF): caled for
+
C24H19NO2 [M]+: 353.1416, found: 353.1409.
8ꢀFluoroꢀ11ꢀ(4ꢀmethoxyphenyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline
compound was prepared
(3d).
The
from
(5ꢀfluoroꢀ2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)methanol and 2ꢀazidobenzaldehyde
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following the general procedure. The product 3d was obtained in 63% yield (45 mg)
5
6
7
as a yellow foam after column chromatography (eluent = petroleum ether/ethyl
8
9
1
o
acetate 10:1 v/v); H NMR (400 MHz, CDCl3, 25 C):
0.64 Hz, 1H), 8.05 (d, = 8.40 Hz, 1H), 7.66ꢀ7.70 (m, 1H), 7.64 (d,
7.48 (t, = 7.60 Hz, 1H), 6.97 (d, = 8.72 Hz, 2H), 6.94 (d, =2.56 Hz, 1H), 6.89 (d,
= 5.36 Hz, 1H), 6.87 (d,
= 5.36 Hz, 1H), 5.29 (s, 2H), 3.87 (s, 3H); 13C NMR
(100.6 MHz, CDCl3, 25 oC):
162.9, 160.5, 160.3, 158.7, 157.2, 147.9, 133.7, 132.6,
δ
8.17 (dd, J1 = 8.24 Hz, J2
=
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
J
J
= 8.68 Hz, 2H),
J
J
J
J
J
δ
132.5, 131.0, 130.3, 129.0, 128.4, 128.3, 125.9, 125.7, 125.6, 121.7, 119.2, 115.1,
114.9, 114.2, 112.3, 112.0, 111.8, 69.2, 55.4; HRMS (EI, TOF): caled for
C23H16FNO2 [M]+: 357.1165, found: 357.1164.
+
11ꢀ(4ꢀMethoxyphenyl)ꢀ8ꢀ(trifluoromethyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline (3e).
The
compound
was
prepared
from
and
(2ꢀ((4ꢀmethoxyphenyl)ethynyl)ꢀ5ꢀ(trifluoromethyl)phenyl)methanol
2ꢀazidobenzaldehyde following the general procedure. The product 3e was obtained in
75% yield (61 mg) as a yellow foam after column chromatography (eluent =
petroleum ether/ethyl acetate 10:1 v/v); 1H NMR (400 MHz, CDCl3, 25 oC):
δ
8.19 (d,
=8.68
= 8.52 Hz, 1H), 6.98
J
= 7.60 Hz, 1H), 8.07 (d,
Hz, 2H), 7.48ꢀ7.52 (m, 2H), 7.30 (d,
(d,
106.6, 160.1, 157.5, 148.3, 133.3, 133.2, 131.1, 131.0, 130.6, 129.1, 126.6, 126.1,
J
= 8.40 Hz, 1H), 7.72 (t,
J
= 7.00 Hz, 1H), 7.64 (d,
J
J
= 8.24 Hz, 1H), 7.01 (d,
J
J
=8.68 Hz, 2H), 5.37 (s, 2H), 3.88 (s, 3H); 13C NMR (100.6 MHz, CDCl3, 25 oC):
δ
125.0, 124.9, 122.0, 121.9, 121.9, 119.4, 114.4, 111.9, 69.4, 55.5; HRMS (EI, TOF):
caled for C24H16F3NO2 [M]+: 407.1133, found: 407.1131.
+
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9ꢀFluoroꢀ11ꢀ(4ꢀmethoxyphenyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline
(3f).
The
5
6
7
compound
was
prepared
from
8
9
(4ꢀfluoroꢀ2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)methanol and 2ꢀazidobenzaldehyde
following the general procedure. The product 3f was obtained in 70% yield (50 mg)
as a yellow solid after column chromatography (eluent = petroleum ether/ethyl acetate
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
1
o
10:1 v/v); Mp: 150ꢀ152 C; H NMR (400 MHz, CDCl3, 25 C):
Hz, 1H), 8.06 (d, = 8.40 Hz, 1H), 7.70 (t, = 7.60 Hz,, 1H), 7.66 (d,
2H), 7.49 (t, = 7.16 Hz,, 1H), 7.19ꢀ7.22 (m, 1H), 6.99 (d,
δ
8.19 (d,
J = 8.20
J
J
J
= 8.40 Hz,
J
J
=8.44 Hz, 2H), 6.88ꢀ6.93
13
(m, 1H), 6.60 (dd, J1 = 10.88 Hz, J2 = 2.40 Hz, 1H), 5.30 (s, 2H), 3.88 (s, 3H); C
o
NMR (100.6 MHz, CDCl3, 25 C):
δ 163.6, 161.2, 160.5, 159.4, 157.4, 148.1, 133.2,
131.7, 131.6, 131.0, 130.7, 129.1, 126.3, 126.2, 125.9, 121.9, 119.1, 114.3, 114.1,
113.8, 113.5, 113.2, 112.1, 112.0, 69.2, 55.4; HRMS (EI, TOF): caled for
+
C23H16FNO2 [M]+: 357.1165, found: 357.1167.
9ꢀChloroꢀ11ꢀ(4ꢀmethoxyphenyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline
compound was prepared
(3g).
The
from
(4ꢀchloroꢀ2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)methanol and 2ꢀazidobenzaldehyde
following the general procedure. The product 3g was obtained in 60% yield (45 mg)
as a yellow solid after column chromatography (eluent = petroleum ether/ethyl acetate
10:1 v/v); Mp: 173ꢀ176 oC; 1H NMR (400 MHz, CDCl3, 25 oC):
Hz, 2 = 0.80 Hz, 1H), 8.08 (d, = 8.40 Hz, 1H), 7.73 (t, = 7.60 Hz, 1H), 7.67 (d,
= 8.76 Hz, 2H), 7.49ꢀ7.54 (m, 1H), 7.20 (d, = 1.04 Hz, 2H), 7.02 (d, =8.76 Hz,
δ 8.20 (dd, J1 = 8.28
J
J
J
J
J
J
2H), 6.87 (s, 1H), 5.32 (s, 2H), 3.91 (s, 3H); 13C NMR (100.6 MHz, CDCl3, 25 oC):
δ
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160.6, 159.6, 157.4, 148.3, 133.9, 133.3, 131.4, 131.0, 130.7, 129.2, 128.6, 127.0,
126.5, 126.1, 125.9, 121.9, 119.2, 114.4, 111.9, 69.2, 55.6; HRMS (EI, TOF): caled
7
8
9
for C23H16ClNO2 [M]+: 373.0870, found: 373.0866.
+
10
11
12
13
14
15
16
17
18
19
20
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23
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37
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41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
11ꢀ(4ꢀMethoxyphenyl)ꢀ6ꢀmethylꢀ6Hꢀisochromeno[4,3ꢀc]quinoline
(3h).
The
compound was prepared from 1ꢀ(2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)ethanꢀ1ꢀol and
2ꢀazidobenzaldehyde following the general procedure. The product 3h was obtained
in 57% yield (40 mg) as a yellow foam after column chromatography (eluent =
petroleum ether/ethyl acetate 10:1 v/v); 1H NMR (400 MHz, CDCl3, 25 oC):
= 7.96 Hz, 1H), 8.05 (d, = 8.32 Hz, 1H), 7.66ꢀ7.70 (m, 3H), 7.49ꢀ7.46 (m, 1H),
7.22ꢀ7.25 (m, 2H), 7.02ꢀ7.06 (m, 1H), 6.94ꢀ6.98 (m, 3H), 5.45 (q, = 6.56 Hz, 2H),
3.84 (s, 3H). 1.87 (d,
= 6.56 Hz, 3H); 13C NMR (100.6 MHz, CDCl3, 25 oC): 160.3,
δ 8.21 (d,
J
J
J
J
158.2, 157.4, 148.0, 134.8, 134.1, 131.1, 130.3, 129.0, 128.9, 127.6, 127.3, 126.8,
125.7, 123.6, 121.9, 119.7, 114.2, 112.7, 75.2, 55.5, 18.9; HRMS (EI, TOF): caled for
+
C24H19NO2 [M]+: 353.1416, found: 353.1415.
1ꢀPhenylꢀ6Hꢀisochromeno[4,3ꢀc]quinoline (3i). The compound was prepared
from (2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)methanol and 2ꢀazidobenzaldehyde
following the general procedure. The product 3i was obtained in 40% yield (25 mg) as
a yellow foam after column chromatography (eluent = petroleum ether/ethyl acetate
25:1 v/v); 1H NMR (400 MHz, CDCl3, 25 oC):
δ 8.21 (dd, J1 = 8.24 Hz, J2 = 0.76 Hz,
1H), 8.08 (d, = 8.44 Hz, 1H), 7.68ꢀ7.73 (m, 3H), 7.48ꢀ7.52 (m, 1H), 7.43ꢀ7.45 (m,
J
3H), 7.18ꢀ7.23 (m, 2H), 6.99ꢀ7.03 (m, 1H), 6.82 (d,
J = 7.92 Hz, 1H), 5.35 (s, 2H);
o
13C NMR (100.6 MHz, CDCl3, 25 C):
δ 159.3, 157.9, 147.9, 141.5, 130.5, 130.3,
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129.6, 129.3, 129.2, 128.8, 128.7, 127.9, 127.1, 126.6, 125.9, 124.8, 121.8, 119.5,
113.0, 69.8; HRMS (EI, TOF): caled for C22H15NO+ [M]+: 309.1154, found: 309.1150.
11ꢀ(pꢀTolyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline (3j). The compound was prepared
from (2ꢀ(pꢀtolylethynyl)phenyl)methanol and 2ꢀazidobenzaldehyde following the
general procedure. The product 3j was obtained in 58% yield (37 mg) as a yellow
foam after column chromatography (eluent = petroleum ether/ethyl acetate 10:1 v/v);
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1H NMR (400 MHz, CDCl3, 25 oC):
δ 8.19 (d, J = 8.00 Hz, 1H), 8.06 (d, J = 8.44 Hz,
1H), 7.66ꢀ7.70 (m, 1H), 7.61 (d,
J
= 8.00 Hz, 2H), 7.46ꢀ7.50 (m, 1H), 7.17ꢀ7.23 (m,
13
4H), 7.01ꢀ7.05 (m, 1H), 6.89 (d,
J
= 7.92 Hz, 1H), 5.33 (s, 2H), 2.42 (s, 3H); C
o
NMR (100.6 MHz, CDCl3, 25 C):
δ 159.2, 157.9, 147.9, 138.8, 138.6, 130.5, 130.3,
129.6, 129.5, 129.4, 129.1, 127.9, 127.1, 126.6, 125.9, 124.9, 121.8, 119.4, 113.0,
69.8, 21.5; HRMS (EI, TOF): caled for C23H17NO+ [M]+: 323.1310, found: 323.1312.
1ꢀ(4ꢀEthylphenyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline (3k). The compound was
prepared
from
(2ꢀ((4ꢀpentylphenyl)ethynyl)phenyl)methanol
and
2ꢀazidobenzaldehyde following the general procedure. The product 3k was obtained
in 43% yield (33 mg) as a yellow foam after column chromatography (eluent =
petroleum ether/ethyl acetate 10:1 v/v); 1H NMR (400 MHz, CDCl3, 25 oC):
= 8.28 Hz, 1H), 8.07 (d, = 8.44 Hz, 1H), 7.69 (t, = 7.60 Hz, 1H), 7.62 (d,
Hz, 2H), 7.48 (t, = 7.56 Hz, 1H), 7.17ꢀ7.23 (m, 4H), 7.01 (t, = 7.32 Hz, 1H),6.86
(d, =8.00 Hz, 1H), 5.33 (s, 2H), 2.67 (t, = 7.48 Hz, 2H), 1.61ꢀ1.68 (m, 2H),
1.32ꢀ1.35 (m, 4H), 0.90 (t,
= 6.76 Hz, 3H); 13C NMR (100.6 MHz, CDCl3, 25 oC):
δ
8.20 (d,
J
J
J
J
=8.04
J
J
J
J
J
δ
159.2, 158.1, 148.0, 143.8, 138.8, 130.5, 130.3, 129.6, 129.5, 129.2, 128.9, 127.9,
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127.1, 126.6, 125.9, 124.9, 121.8, 119.5, 113.1, 69.8, 35.8, 31.5, 31.1, 22.6, 14.2;
HRMS (EI, TOF): caled for C27H25NO+ [M]+: 379.1936, found: 379.1935.
7
8
9
11ꢀ(4ꢀ(tertꢀButyl)phenyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline (3l). The compound
was prepared from (2ꢀ((4ꢀ(tertꢀbutyl)phenyl)ethynyl)phenyl)methanol and
2ꢀazidobenzaldehyde following the general procedure. The product 3l was obtained in
51% yield (37 mg) as a yellow foam after column chromatography (eluent =
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
o
petroleum ether/ethyl acetate 10:1 v/v); H NMR (400 MHz, CDCl3, 25 C):
δ 8.16
(dd, 1 = 8.28 Hz, 2 = 0.80 Hz, 1H), 8.07 (d, = 8.40 Hz, 1H), 7.63ꢀ7.70 (m, 3H),
J
J
J
7.44ꢀ7.50 (m, 3H), 7.17ꢀ7.24 (m, 2H), 7.00ꢀ7.04 (m, 1H), 6.90 (d,
J
=7.92 Hz, 1H),
δ 159.2, 157.9,
o
5.34 (s, 2H), 1.36 (s, 9H); 13C NMR (100.6 MHz, CDCl3, 25 C):
151.9, 147.9, 138.5, 130.4, 130.2, 129.4, 129.2, 129.1, 127.9, 127.0, 126.6, 125.8,
125.6, 124.8, 121.8, 119.4, 112.9, 69.7, 34.8, 31.4; HRMS (EI, TOF): caled for
C26H23NO+ [M]+: 365.1780, found: 365.1779.
11ꢀ(4ꢀ(Octyloxy)phenyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline (3m). The compound
was
prepared
from
(2ꢀ((4ꢀ(octyloxy)phenyl)ethynyl)phenyl)methanol
and
2ꢀazidobenzaldehyde following the general procedure. The product 3m was obtained
in 66% yield (58 mg) as a yellow foam after column chromatography (eluent =
petroleum ether/ethyl acetate 10:1 v/v); 1H NMR (400 MHz, CDCl3, 25 oC):
= 8.28 Hz, 1H), 8.05 (d, = 8.44 Hz, 1H), 7.65ꢀ7.70 (m, 3H), 7.45ꢀ7.49 (m, 1H),
7.17ꢀ7.22 (m, 2H), 7.02ꢀ7.06 (m, 1H), 6.92ꢀ6.96 (m, 3H), 5.32 (s, 2H), 4.01 (t,
δ 8.18 (d,
J
J
J
=
6.64 Hz, 2H), 1.81 (m, 2H), 1.47 (m, 2H), 1.33 (m, 8H), 0.89 (t, J
= 6.84 Hz, 3H); 13C
o
NMR (100.6 MHz, CDCl3, 25 C):
δ
159.9, 159.2, 157.6, 147.9, 133.7, 131.0, 130.4,
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130.3, 129.6, 128.9, 127.9, 127.0, 126.5, 125.7, 124.8, 121.8, 119.3, 114.7, 112.9,
69.7, 68.1, 53.5, 31.8, 29.4, 29.3, 26.1, 22.7, 14.1; HRMS (EI, TOF): caled for
7
8
9
C30H31NO2 [M]+: 437.2355, found: 437.2358.
+
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
11ꢀ(Thiophenꢀ2ꢀyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline (3n). The compound was
prepared from (2ꢀ(thiophenꢀ2ꢀylethynyl)phenyl)methanol and 2ꢀazidobenzaldehyde
following the general procedure. The product 3n was obtained in 59% yield (37 mg)
as a yellow foam after column chromatography (eluent = petroleum ether/ethyl
1
o
acetate 10:1 v/v). H NMR (400 MHz, CDCl3, 25 C):
8.02 (d, = 8.44 Hz, 1H), 7.66ꢀ7.70 (m, 1H), 7.45ꢀ7.49 (m, 2H), 7.37 (dd, J1 = 3.60
Hz, J2 = 0.96 Hz,1H), 7.32 (d, = 7.92 Hz, 1H), 7.27 (m, 2H), 7.14ꢀ7.16 (m, 1H),
7.03ꢀ7.05 (m, 1H), 5.32 (s, 2H); 13C NMR (100.6 MHz, CDCl3, 25 oC):
159.3, 150.9,
δ 8.16 (d, J = 8.24 Hz, 1H),
J
J
δ
148.1, 144.2, 130.6, 130.5, 129.3, 129.1, 129.0, 128.1, 127.9, 127.6, 127.5, 126.2,
126.1, 125.1, 121.8, 119.5, 113.1, 69.9; HRMS (EI, TOF): caled for C20H13NOS+ [M]+:
315.0718, found: 315.0719.
4ꢀChloroꢀ11ꢀ(4ꢀmethoxyphenyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline
(3o).
The
compound was prepared from (2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)methanol and
2ꢀazidoꢀ6ꢀchlorobenzaldehyde following the general procedure. The product 3o was
obtained in 47% yield (35 mg) as a yellow foam after column chromatography (eluent
1
= petroleum ether/ethyl acetate 10:1 v/v). H NMR (400 MHz, CDCl3, 25 oC):
δ
7.96
(dd, J1 = 7.72 Hz, J2 = 1.84 Hz, 1H), 7.66 (d,
J = 8.68 Hz, 2H), 7.49ꢀ7.51 (m, 2H),
7.24ꢀ7.25 (m, 2H), 7.03ꢀ7.07 (m, 1H), 6.91ꢀ6.96 (m, 3H), 5.32 (s, 2H), 3.87 (s, 3H);
o
13C NMR (100.6 MHz, CDCl3, 25 C):
δ 160.5, 159.9, 159.7, 149.8, 133.3, 131.2,
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130.6, 129.4, 129.2, 129.1, 128.7, 128.6, 127.9, 127.3, 126.8, 124.7, 117.5, 114.3,
5
6
7
+
114.1, 69.5, 55.4; HRMS (EI, TOF): caled for C23H16ClNO2 [M]+: 373.0870, found:
8
9
373.0871.
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3ꢀChloroꢀ11ꢀ(4ꢀmethoxyphenyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline
(3p).
The
compound was prepared from (2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)methanol and
2ꢀazidoꢀ5ꢀchlorobenzaldehyde following the general procedure. The product 3p was
obtained in 72% yield (54 mg) as a yellow solid after column chromatography (eluent
o
1
= petroleum ether/ethyl acetate 10:1 v/v). Mp: 183ꢀ186 C; H NMR (400 MHz,
o
CDCl3, 25 C):
δ 8.16 (d, J = 2.24 Hz, 1H), 7.97 (d, J = 8.96 Hz, 1H), 7.66 (d, J =
8.76 Hz, 2H), 7.61 (dd, J1 =8.96 Hz, J2 =2.40 Hz, 1H), 7.22ꢀ7.24 (m, 2H), 7.04ꢀ7.08
(m, 1H), 6.96 (d,
J
= 8.76 Hz, 2H),6.93 (d,
J
=8.12 Hz, 1H), 5.37 (s, 2H), 3.88 (s, 3H);
o
13C NMR (100.6 MHz, CDCl3, 25 C):
δ 160.4, 158.3, 157.7, 146.3, 133.6, 131.5,
131.1, 130.7, 130.4, 129.2, 128.1, 127.4, 126.5, 124.9, 120.9, 120.1, 114.2, 113.6,
+
69.8, 55.4; HRMS (EI, TOF): caled for C23H16ClNO2 [M]+: 373.0870, found:
373.0867.
2ꢀChloroꢀ11ꢀ(4ꢀmethoxyphenyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline
(3q).
The
compound was prepared from (2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)methanol and
2ꢀazidoꢀ5ꢀchlorobenzaldehyde following the general procedure. The product 3q was
obtained in 58% yield (43 mg) as a yellow foam after column chromatography (eluent
1
o
= petroleum ether/ethyl acetate 10:1 v/v); H NMR (400 MHz, CDCl3, 25 C):
(d, = 8.84 Hz, 1H), 8.05 (d, = 1.92 Hz, 1H), 7.66 (d, = 8.76 Hz, 2H), 7.41 (dd, J1
= 8.80 Hz, 2 = 2.00 Hz, 1H), 7.21ꢀ7.23 (m, 2H), 7.03ꢀ7.07 (m, 1H), 6.96 (d, J = 8.76
δ 8.11
J
J
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Hz, 2H), 6.92 (d,
CDCl3, 25 oC):
J
= 7.92 Hz, 1H), 5.33 (s, 2H), 3.88 (s, 3H); 13C NMR (100.6 MHz,
δ
160.5, 159.2, 158.6, 148.4, 136.1, 133.5, 131.1, 130.3, 129.2, 128.1,
7
8
9
128.0, 127.3, 126.6, 126.4, 124.9, 123.3, 117.7, 114.1, 113.1, 69.8, 55.4; HRMS (EI,
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+
TOF): caled for C23H16ClNO2 [M]+: 373.0870, found: 373.0868.
3ꢀBromoꢀ11ꢀ(4ꢀmethoxyphenyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline
(3r).
The
compound was prepared from (2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)methanol and
2ꢀazidoꢀ5ꢀbromobenzaldehyde following the general procedure. The product 3r was
obtained in 56% yield (46 mg) as a yellow solid after column chromatography (eluent
o
1
= petroleum ether/ethyl acetate 10:1 v/v). Mp: 143ꢀ146 C; H NMR (400 MHz,
o
CDCl3, 25 C):
δ
8.34 (s, 1H), 7.91 (d,
=6.60 Hz, 2H), 7.06 (t,
= 8.08 Hz, 1H), 5.33 (s, 2H), 3.88 (s, 3H); 13C NMR
160.6, 158.3, 157.9, 146.6, 133.7, 131.2, 130.9, 130.5,
J
= 8.84 Hz, 1H), 7.73 (d,
J = 8.80 Hz, 1H),
7.66 (d,
= 8.36 Hz, 2H), 6.93 (d,
(100.6 MHz, CDCl3, 25 oC):
J
= 8.24 Hz, 2H), 7.23 (d,
J
J
= 6.48 Hz, 1H), 6.96 (d,
J
J
δ
129.2, 128.2, 127.6, 126.6, 125.1, 124.4, 120.6, 119.7, 114.3, 113.7, 69.9, 55.5;
+
HRMS (EI, TOF): caled for C23H16BrNO2 [M]+: 417.0364, found: 417.0365.
11ꢀ(4ꢀMethoxyphenyl)ꢀ3ꢀ(trifluoromethyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline (3s).
The compound was prepared from (2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)methanol
and 2ꢀazidoꢀ5ꢀ(trifluoromethyl)benzaldehyde following the general procedure. The
product 3s was obtained in 57% yield (46 mg) as a yellow foam after column
1
chromatography (eluent = petroleum ether/ethyl acetate 10:1 v/v); H NMR (400
o
MHz, CDCl3, 25 C):
δ 8.35 (s, 1H), 8.28 (d, J = 8.68 Hz, 1H), 7.68 (d, J = 8.72 Hz,
2H), 7.63 (dd, J1 =8.68 Hz, J2 =1.44 Hz, 1H), 7.24ꢀ7.25 (m, 2H), 7.05ꢀ7.09 (m, 1H),
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6.95ꢀ6.99 (m, 3H), 5.36 (s, 2H), 3.88 (s, 3H); 13C NMR (100.6 MHz, CDCl3, 25 oC):
δ
5
6
7
8
9
160.6, 158.9, 158.8, 146.9, 133.4, 132.0, 131.7, 131.1, 130.4, 129.0, 128.2, 127.7,
128.6, 128.7, 128.6, 125.1, 123.2, 121.3, 121.2, 121.1, 114.4, 114.2, 69.9, 55.4;
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+
HRMS (EI, TOF): caled for C24H16F3NO2 [M]+: 407.1133, found: 407.1131.
Methyl
(3t).The
(2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)methanol
11ꢀ(4ꢀmethoxyphenyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinolineꢀ3ꢀcarboxylate
compound
was
prepared
and
from
methyl
4ꢀazidoꢀ3ꢀformylbenzoate following the general procedure. The product 3t was
obtained in 55% yield (63 mg) as a yellow foam after column chromatography (eluent
= petroleum ether/ethyl acetate 10:1 v/v); H NMR (400 MHz, CDCl3, 25 oC) δ 8.94
1
(s, 1H), 8.26 (d,
J
= 8.84 Hz, 1H), 8.06 (d,
J = 8.92 Hz, 1H), 7.70 (d, J = 8.36 Hz, 2H),
7.22 (d, =7.20 Hz, 2H), 7.07 (t,
J
J
= 6.96 Hz, 1H), 6.94ꢀ6.98 (m, 3H), 5.37 (s, 2H),
3.99 (s, 3H), 3.88 (s, 3H); 13C NMR (100.6 MHz, CDCl3, 25 oC): 166.9, 160.7, 160.2,
159.7, 138.8, 136.0, 131.3, 130.4, 130.0, 129.3, 129.2, 128.2, 127.6, 127.2, 126.5,
125.4, 125.1, 118.8, 114.3, 113.6, 69.9, 55.5, 52.5; HRMS (EI, TOF): caled for
C25H19NO4 [M]+: 397.1314, found: 397.1310.
+
2ꢀThoxyꢀ11ꢀ(4ꢀmethoxyphenyl)ꢀ6Hꢀisochromeno[4,3ꢀc]quinoline
(3u).
The
compound was prepared from (2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)methanol and
2ꢀazidoꢀ4ꢀmethoxybenzaldehyde fTollowing the general procedure. The product 3u
was obtained in 60% yield (44 mg) as a yellow foam after column chromatography
(eluent = petroleum ether/ethyl acetate 5:1 v/v); 1H NMR (400 MHz, CDCl3, 25 oC):
δ
8.07 (d,
J
= 9.08 Hz, 1H), 7.65 (d,
J
= 8.68 Hz, 2H), 7.40 (d, J = 2.40 Hz, 1H),
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7.15ꢀ7.23 (m, 2H), 7.11 (d,
2H), 6.89 (d,
= 8.12 Hz, 1H), 5.30 (s, 2H), 3.95 (s, 3H), 3.87 (s, 3H); 13C NMR
(100.6 MHz, CDCl3, 25 oC):
161.6, 160.2, 159.4, 157.9, 149.8, 133.9, 133.0, 130.9,
J = 9.08 Hz, 1H), 7.01ꢀ7.05 (m, 1H), 6.96 (d, J = 8.68 Hz,
J
δ
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130.2, 129.7, 127.9, 126.7, 126.3, 124.9, 123.1, 118.6, 114.1, 113.9, 111.5, 107.3, 69.7,
55.6, 55.4; HRMS (EI, TOF): caled for C24H19NO3 [M]+: 369.1365, found: 369.1364.
+
11ꢀ(4ꢀEthoxyphenyl)ꢀ2ꢀmethylꢀ6Hꢀisochromeno[4,3ꢀc]quinoline
(3v).
The
compound was prepared from (2ꢀ((4ꢀmethoxyphenyl)ethynyl)phenyl)methanol and
2ꢀazidoꢀ4ꢀmethylbenzaldehyde following the general procedure. The product 3v was
obtained in 74% yield (52 mg) as a yellow foam after column chromatography (eluent
1
= petroleum ether/ethyl acetate 10:1 v/v); H NMR (400 MHz, CDCl3, 25 oC):
δ
8.06
1 =8.44 Hz, J2
= 8.68 Hz, 2H),
(d,
=1.24 Hz, 1H), 7.16ꢀ7.23 (m, 2H), 7.03 (t,
6.90 (d,
MHz, CDCl3, 25 oC):
J = 8.40 Hz, 1H), 7.84 (s, 1H), 7.66 (d, J = 8.72 Hz, 2H), 7.30 (dd, J
J
= 8.08 Hz, 1H), 6.95 (d,
J
13
J
=7.92 Hz, 1H), 5.30 (s, 2H), 3.87 (s, 3H), 2.54 (s, 3H); C NMR (100.6
δ
160.2, 159.3, 157.5, 148.2, 140.7, 134.0, 131.1, 130.3, 129.7,
128.1, 127.9, 126.8, 126.4, 142.8, 121.5, 117.2, 114.0, 112.2, 69.7, 55.4, 21.9; HRMS
+
(EI, TOF): caled for C24H19NO2 [M]+: 353.1416, found: 353.1411.
Supporting Information
The copies of 1H NMR, 13C NMR spectra of products (PDF), crystallographic data for
3g (CIF). This material is available free of charge via the Internet at
http://pubs.acs.org.T
Acknowledgements
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This work was supported by the National Natural Science Foundation of China
(Project Nos. 21372072, 21421004, 21561162003 and 21672059), the Program for
Eastern Scholar Distinguished Professor, the Fundamental Research Funds for the
Central Universities and the Programme of Introducing Talents of Discipline to
Universities (B16017).
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