Synthesis of 1,4-dihydroquinoline derivatives under transition-metal-free conditions and their diverse applications

Article abstract of DOI:10.1039/c4ob00475b

A transition-metal-free process for the synthesis of 1,4-dihydroquinoline derivatives starting from simple enaminones with aldehydes via intermolecular cascade cyclization in a one-pot protocol is developed. This methodology affords a variety of products in moderate to good yields. Particularly, the use of the enaminone fragment in 1,4-dihydroquinoline derivatives 3 as a leaving group for further diverse applications with C-nucleophiles is proved to be feasible. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ob00475b

Organic &
Biomolecular Chemistry
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PAPER
Synthesis of 1,4-dihydroquinoline derivatives
under transition-metal-free conditions and their
diverse applications†
Cite this: Org. Biomol. Chem., 2014,
12, 4243
Xue-Qiang Chu, You Zi, Hua Meng, Xiao-Ping Xu* and Shun-Jun Ji*
A transition-metal-free process for the synthesis of 1,4-dihydroquinoline derivatives starting from simple
enaminones with aldehydes via intermolecular cascade cyclization in a one-pot protocol is developed.
This methodology affords a variety of products in moderate to good yields. Particularly, the use of the
enaminone fragment in 1,4-dihydroquinoline derivatives 3 as a leaving group for further diverse appli-
cations with C-nucleophiles is proved to be feasible.
Received 3rd March 2014,
Accepted 21st April 2014
DOI: 10.1039/c4ob00475b
www.rsc.org/obc
The transition-metal (TM)-catalyzed cross-coupling reactions
are direct and powerful strategies for the construction of new
C–N bonds, which are featured in the synthesis of various
pharmaceuticals and biologically active molecules.1 Although
some success has been achieved with Pd (Buchwald–Hartwig
amination),2 Cu (Ullmann or Goldberg-type reaction),3 Fe,4 or
Ni5 catalysts for this transformation in the past few decades,
they still suffer from a number of drawbacks: (i) use of expen-
sive catalysts, ligands or additives; (ii) need harsh conditions
(e.g., under inert gas protection); (iii) limited starting materials
(organometallic reagents for Caryl–N coupling);6 (iv) trace-metal
contamination (especially in production of APIs).7 Hence,
developing a cheaper, less toxic, and eco-friendly methodology
is highly desirable, and in this context, TM-free processes
aroused extensive attention.8–15 For instance, Tu,10 Bolm,11
and others12,14 described the base-promoted amination of
aryl halides with N-nucleophiles. Considerable efforts
have been directed towards the formation of heterocycles,13
especially through intra or intermolecular N-arylation.11c–f,14
Quinoline, as a privileged skeleton, is a core element of
many pharmaceutically relevant compounds and natural pro-
ducts.15 Quinoline derivatives have been widely used in the
manufacture of dyes and the discovery of experimental
drug candidates.16 Among them, 1,4-dihydroquinolines have
attracted special research interest,17 because of their potential
utilities as calcium channel modulators (1,4-DHPs),17a–c brain
delivery carriers,17d antiurease compounds,17e HIV-1 inhibi-
Scheme 1 Acid or transition-metal catalyzed synthesis of quinoline
derivatives.
tors,17f the M1 muscarinic receptor modulators,17g and organic
optoelectronic materials.17h Traditional strategies for the
assembly of the quinoline ring system involve an initial inter-
molecular reaction of an aniline with a carbonyl compound or
its precursor, which suffered from a lack of readily available
starting materials (o-aminobenzaldehydes) and harsh reaction
conditions (e.g. Scheme 1, A).18 Recently, transition-metal-
catalyzed syntheses of quinoline derivatives have also been
developed. Palladium, rhodium, ruthenium, and iron salts or
complexes are used as catalysts in combination with strong
bases.19 Our goal is to seek for an efficient method for the
synthesis of quinoline derivatives by transition-metal-free
intermolecular cyclization from simple and readily accessible
substrates.
Considering our previous findings (Scheme 1, B),19a,g we
designed A as a building block, which could be generated via
the Baylis–Hillman reaction20 from β-enaminone and benz-
aldehyde, and then under basic conditions, the ortho-substitu-
ent of the aldehyde serving as a leaving group leads to the
final ring-closed product, the 1,4-dihydroquinoline derivative
(Scheme 2).11c–f
To carry out our trials, β-enaminone 2a (easily prepared
from the corresponding amine with diketone) and o-bromo-
benzaldehyde were selected as model substrates. To our
delight, the desired product 1,4-dihydroquinoline 3aa could be
obtained in 33% LC-yield without the involvement of any
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry,
Chemical Engineering and Materials Science & Collaborative Innovation Center of
Suzhou Nano Science and Technology, Soochow University, Suzhou, 215123,
People’s Republic of China. E-mail: xuxp@suda.edu.cn, shunjun@suda.edu.cn;
Fax: (+)86-512-65880307; Tel: +86-512-65880307
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4ob00475b
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Table 2 Synthesis of 1,4-dihydroquinoline derivativesa
Entry R1
R2
Time (h) Product Yieldb (%)
Scheme 2 TM-free synthesis of 1,4-dihydroquinoline derivatives.
Table 1 Optimization of the reaction conditionsa
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
H
H
H
H
4-OMe
4-OCF3
3,4-Methylenedioxy 14
12
12
3aa
3ab
3ac
3ad
3ae
3af
70
68
68
75
61
22
73
75
72
75
68
Trace
75
74
66
54
50
4-Me
3-Me
2-Me
H
4-Cl
3-Cl
4-Br
4-I
16
16
17
17
21
20
18
18
24
10
10
12
11
18
3ag
3ah
3ai
3aj
3ak
3al
3ba
3ca
3da
3ea
3fa
9
10
11
12
13
14
15
16
17
4-CN
4-NO2 4-OMe
5-Cl
5-F
4-OMe
4-OMe
Solvent
(2 ml)
Temp.
(°C)
Time
(h)
LC yieldb
(%)
5-OTs 4-OMe
5-OBn 4-OMe
Entry
L
Base
a Reaction conditions:
(0.6 mmol) in 2 mL toluene. b Isolated yield.
1 (0.3 mmol), 2 (0.5 mmol) and K3PO4
1
2
3
4
5
6
7
8
Br
Cl
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
t-BuOK
NaOAc
—
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
MeCN
110
110
110
110
110
110
110
110
110
110
120
Reflux
Reflux
120
12
12
12
24
12
24
24
12
24
12
12
12
12
12
12
33
<10
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
60(52c)
59
41
39
39
Trace
43
various substituted enaminones with o-nitrobenzaldehydes, as
shown in Table 2. The 3-aryl enaminones bearing functional
groups such as methoxy (2a), trifluoromethoxy (2b), 3,4-
methylenedioxy (2c), methyl (2d–e), as well as halogens (2h–k)
were equally efficient, giving the desired 1,4-dihydroquinoline
derivatives 3 in very similar good yields (61–75%) (Table 2,
entries 1–5 and 8–11). It was found that the reaction of 1a and
2f with ortho steric hindrance could also lead to the product
3af, albeit in 22% yield (Table 2, entry 6). Enaminones 2g
KOH
9
DABCOd
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
10
11e
12e
13e
14e
15e
65(54c)
79(70c)
(30c)
Trace
(23c)
Trace
EtOH
DMF
DMSO
120
a Reaction conditions: 1a (0.25 mmol), 2a (0.5 mmol), solvent (2 mL),
and base (2 equiv.). b Yields were determined by LC with an internal reacting with 1a furnished the corresponding products 3ag in
standard (biphenyl) as the ratio between the formed products and the
73% yield (Table 2, entry 7). However, substrate 2l with a
initial amount of the limiting reactant. c Isolated yield. d DABCO =
triethylenediamine. e 0.3 mmol 1a was used.
strong electron-withdrawing group had dramatic detrimental
effects on the transformation, likely due to the low nucleophi-
licity of the resulting anion for further cyclization (Table 2,
transition-metal catalyst (Table 1, entry 1). When the bromo- entry 12). In addition, nitro (1b), halogens (1c–d), OTs (1e),
substituent of 1a was changed to a chloro group, a lower yield and OBn (1f) substituents on the 2-nitrobenzaldehyde were
was obtained (Table 1, entry 2). Interestingly, the reaction also found to be suitable for the present cascade reactions to
employing 2-nitrobenzaldehyde performed better leading to afford the expected products 3ba, 3ca, 3da, 3ea, and 3fa in
3aa in 60% LC-yield (Table 1, entry 3). Further optimization 75%, 74%, 66%, 54%, and 50% yields, respectively (Table 2,
studies revealed that the product formation was dramatically entries 13–17).
affected by the base (e.g., Cs2CO3, t-BuOK, NaOAc, KOH,
Recently, the use of the 1,3-dicarbonyl fragment as a
DABCO and K3PO4) (Table 1, entries 3–10). Among the bases leaving group through C–C bond cleavage has emerged as an
screened, K3PO4 turned out to be the best choice, leading to attractive alternative in organic synthesis.21 We envisioned that
remarkable improvement of the product yield (70% isolated we could apply a similar β-enaminone unit as a leaving group
yield) by increasing the temperature to 120 °C (oil bath temp- through C–C bond cleavage. Therefore, the diverse appli-
erature) in toluene under air (Table 1, entry 11). Moreover, the cations of 1,4-dihydroquinoline derivatives
feasibility of the solvents was also investigated and no better sequently investigated by performing the reaction of 3 with
results were observed in these cases (Table 1, entries 12–15).
indoles 4. The assembly of these important heterocyclic cores
3 were sub-
Under the optimized reaction conditions, the scope of this becomes highly desirable, which might be useful for develop-
intermolecular cyclization reaction was examined using ing libraries of medicinal scaffolds. It was found that the
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Table 3 Reaction of 3 with indoles 4
Scheme 4 Control experiment.
Scheme 3 Reaction of 3 with nitromethane.
Scheme 5 Plausible reaction pathway.
densely functionalized 1,4-dihydroquinoline derivatives 5 were
obtained in 78–91% yields with 10 mol% FeCl3 and 10 mol%
PPh3 (Table 3). Scheme 3 shows that nitromethane could react
smoothly with 1,4-dihydroquinoline derivatives 3 as another
carbon-based nucleophile.
On the basis of above results, a reasonable pathway for the
formation of 1,4-dihydroquinoline derivatives was postulated
in Scheme 5. Firstly, the intermediate I was generated through
a Baylis–Hillman-type reaction20 from benzaldehydes and
enaminones, involving H-transfer and tautomerization of
imine back to the enamine process. This intermediate I under-
went elimination of water to form the corresponding α,β-un-
saturated imine/ketone II, which were susceptible towards
nucleophilic attack of another β-enaminone to give A. Under
the basic conditions, the nitro-substituent of A serving as a
leaving group leads to the final product 3.14d,23 However, the
details regarding nitro group’s elimination are not very clear, it
seems to proceed through an SNAr mechanism. The mechan-
ism from 3 to 5/6 demonstrated in Table 3 and Scheme 3
might involve the following steps: (i) with the promotion of a
catalyst, breaking of a C–C bond of the product 3, in which a
fragment of 2 acts as a leaving group (2 determined by LC-MS
analysis during the reaction), generating thus a carbonium
intermediate B;21 (ii) trapping of B with another nucleophile,
To gain a deeper mechanistic understanding, we tried 1a
with 2a in the absence of potassium phosphate in toluene
under air for 12 h. It was found that intermediate A, rather
than the expected product 3aa, was formed in the system
(determined by LC-MS analysis, Scheme 4, eqn (1)). In the fol-
lowing step, potassium phosphate (2 equiv.) was added to the
reaction for another 12 h, only a trace amount of A remained,
along with the formation of the final ring-closed product 3aa
in 50% yield. These experimental results reveal that intermedi-
ate A plays a central role in this intermolecular cascade cycliza-
tion process. Next, when the aldehyde 1g bearing a nitro group
in the meta-position was subjected to the reaction instead
of 1a, no cyclic product 3aa was observed (Scheme 4,
eqn (2)). Although not entirely conclusive, this result
indicates that the reaction does not proceed via an aryne
intermediate.22
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such as indole or nitromethane, which led to the formation of
the product 5 or 6.
10-(4-Methoxyphenyl)-9-(2-(4-methoxyphenylamino)-4,4-dimethyl-
6-oxocyclohex-1-enyl)-3,3-dimethyl-3,4,9,10-tetrahydroacridin-
In conclusion, we have developed a transition-metal-free 1(2H)-one (3aa). Yellow solid. Mp = 218–220 °C. IR (KBr) ν =
intermolecular cyclization reaction of aldehydes with enami- 3218, 3063, 2955, 2871, 1613, 1589, 1512, 1458, 1389, 833,
1
nones. By using this methodology, a variety of 1,4-dihydroqui- 756 cm−1. H NMR (400 MHz, CDCl3): δ = 0.88 (d, J = 8.1 Hz,
noline derivatives were synthesized in moderate to good yields. 6H), 0.98 (s, 6H, 2CH3), 2.00–2.31 (m, 7H), 2.69 (d, J = 16.5 Hz,
Particularly, the application of a β-enaminone unit as a new 1H), 3.84 (s, 3H), 3.90 (s, 3H), 5.10 (s, 1H), 6.14–6.17 (m, 1H),
and useful leaving group through C–C bond cleavage of 1,4- 6.85–6.87 (m, 2H), 6.92 (d, J = 8.6 Hz, 2H), 6.99–7.17 (m, 6H),
dihydroquinoline derivatives was attractive.
7.82 (d, J = 8.5, 1H), 10.01 (s, 1H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 196.7, 195.1, 159.5, 157.0, 156.4, 156.1, 141.2,
133.9, 133.1, 131.9, 131.3, 128.7, 127.7, 126.2, 124.8, 123.1,
119.6, 116.0, 115.7, 114.6, 114.5, 107.4, 55.7, 51.8, 49.9, 42.5,
40.5, 32.7, 32.3, 32.1, 30.1, 29.9, 28.3, 28.1, 26.7 ppm. HRMS
m/z: calcd for C37H40N2O4 [M]+ 576.2988, found: 576.3008.
9-(4,4-Dimethyl-6-oxo-2-(4-(trifluoromethoxy)phenylamino)-
cyclohex-1-enyl)-3,3-dimethyl-10-(4-(trifluoromethoxy)phenyl)-
3,4,9,10-tetrahydroacridin-1(2H)-one (3ab). Yellow solid. Mp =
125.5–126.5 °C. IR (KBr) ν = 2959, 2870, 1591, 1558, 1507,
Experimental
General
Unless otherwise stated, all reagents were purchased from
commercial suppliers and used without further purification.
All reactions were carried out in air and using an undistilled
solvent, without any precautions to exclude air and moisture
unless otherwise noted. Melting points were recorded on elec-
trothermal digital melting point apparatus. IR spectra were
recorded on a FT-IR spectrophotometer using KBr optics. 1H
and 13C NMR spectra were recorded in CDCl3 or DMSO-d6 on
300 MHz, 400 MHz or 600 MHz spectometers. Tetramethyl-
1490, 1392, 1253, 1200, 1156, 1017, 747, 631 cm−1 1H NMR
.
(400 MHz, CDCl3): δ = 0.89 (s, 6H), 1.01 (d, J = 7.2 Hz, 6H),
2.34–1.92 (m, 7H), 2.80 (d, J = 16.3 Hz, 1H), 5.09 (s, 1H),
6.12–6.04 (m, 1H), 6.93–6.85 (m, 2H), 6.98 (dd, J = 9.3, 4.5 Hz,
1H), 7.24–7.16 (m, 4H), 7.33 (d, J = 7.1 Hz, 1H), 7.46–7.38 (m,
2H), 8.03 (d, J = 7.0 Hz, 1H), 10.30 (s, 1H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 197.0, 195.6, 155.3, 155.2, 149.1, 144.6,
140.7, 139.8, 138.7, 132.7, 131.9, 128.7, 127.2, 126.3, 123.4,
122.9, 122.1, 121.9 121.7, 121.3, 119.3, 119.2, 115.5, 107.6,
51.9, 49.8, 42.5, 40.5, 33.1, 32.3, 32.0, 29.9, 28.5, 27.4,
26.4 ppm. HRMS m/z: calcd for C37H35F6N2O4 [M + H]+
685.2501, found 685.2498.
1
silane (TMS) served as the internal standard for H NMR and
CDCl3 or DMSO-d6 was used as the internal standard for 13C
NMR. High resolution mass spectra were obtained using com-
mercial apparatus (ESI source).
General procedure for intermolecular cascade cyclization of
aldehydes with enaminones
o-Nitrobenzaldehyde 1 (0.3 mmol), enaminone 2 (0.5 mmol)
and K3PO4 (0.6 mmol) in 2 mL toluene were stirred at 120 °C
under air for the stipulated time mentioned in Table 2. Upon
completion of the reaction (indicated by TLC), the residue was
directly purified by flash column chromatography using ethyl
acetate and petroleum ether as eluents to afford the pure
product 3.
10-(Benzo[d][1,3]dioxol-5-yl)-9-(2-(benzo[d][1,3]dioxol-5-ylamino)-
4,4-dimethyl-6-oxocyclohex-1-enyl)-3,3-dimethyl-3,4,9,10-tetra-
hydroacridin-1(2H)-one
(3ac). Yellow
solid.
Mp
=
215.9–217.5 °C. IR (KBr) ν = 2953, 2868, 1616, 1587, 1482,
1
1457, 1390, 1270, 1229, 929, 808, 756, 746, 669 cm−1. H NMR
(600 MHz, CDCl3): δ = 0.89 (d, J = 14.0 Hz, 6H), 0.99 (d, J =
11.8 Hz, 6H), 2.10–2.30 (m, 7H), 2.70 (d, J = 16.5 Hz, 1H), 5.06
(s, 1H), 6.01–5.98 (m, 2H), 6.06–6.12 (m, 2H), 6.24 (t, J =
6.4 Hz, 1H), 6.69 (d, J = 7.9 Hz, 1H), 6.76–6.71 (m, 2H), 6.81 (d,
J = 8.1 Hz, 1H), 7.00–6.86 (m, 4H), 7.44 (d, J = 10.1 Hz, 1H),
10.02 (s, 1H). 13C NMR (150 MHz, CDCl3): δ = 196.9, 195.2,
156.9, 156.0, 149.7, 148.3, 148.0, 144.4, 141.2, 135.3, 134.2,
128.8, 127.7, 126.3, 124.5, 123.7, 123.2, 120.0, 116.5, 115.7,
111.6, 111.0, 110.1, 108.5, 107.6, 105.4, 102.1, 101.5, 51.8, 50.0,
42.5, 40.7, 32.8, 32.3, 32.2, 30.1, 30.0, 28.3, 28.2, 26.9 ppm.
HRMS m/z: calcd for C37H37N2O6 [M + H]+ 605.2652, found
605.2663.
General procedure for reaction of 1,4-dihydroquinoline
derivatives 3 with indoles
1,4-Dihydroquinoline derivative
3 (0.3 mmol), indole 4
(0.36 mmol), FeCl3 (0.03 mmol) and PPh3 (0.03 mmol) in 2 mL
DCE (1,2-dichloroethane) were stirred at 80 °C under air for
the stipulated time mentioned in Table 3. Upon completion of
the reaction (indicated by TLC), the residue was directly puri-
fied by flash column chromatography using ethyl acetate and
petroleum ether as eluents to afford the pure product 5.
9-(4,4-Dimethyl-6-oxo-2-(p-tolylamino)cyclohex-1-enyl)-3,3-
dimethyl-10-p-tolyl-3,4,9,10-tetrahydroacridin-1(2H)-one (3ad).
Yellow solid. Mp = 246–248 °C. IR (KBr) ν = 3147, 3029, 2954,
General procedure for reaction of 1,4-dihydroquinoline
derivatives 3 with nitromethane
1,4-Dihydroquinoline derivative
3
(0.3 mmol), FeCl3 2871, 1634, 1589, 1512, 1458, 1389, 810, 756 cm−1 1H NMR
.
(0.03 mmol) and PPh3 (0.03 mmol) in 2 mL nitromethane were (400 MHz, CDCl3): δ = 0.88 (d, J = 5.7 Hz, 6H, 2CH3), 0.99 (d,
stirred at 80 °C under air for 24 h. Upon completion of the J = 8.4 Hz, 6H, 2CH3), 1.98–2.32 (m, 7H), 2.36 (s, 3H, CH3),
reaction (indicated by TLC), the residue was directly purified 2.46 (s, 3H, CH3), 2.80 (d, J = 16.6 Hz, 1H), 5.11 (s, 1H, CH),
by flash column chromatography using ethyl acetate and 6.10–6.14 (m, 1H, ArH), 6.84–7.19 (m, 8H, ArH), 7.32 (d, J =
petroleum ether as eluents to afford the pure product 6.
7.8 Hz, 1H, ArH), 7.38 (d, J = 8.0 Hz, 1H, ArH), 7.77 (d, J =
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7.3 Hz, 1H, ArH), 10.15 (s, 1H, NH) ppm. 13C NMR (100 MHz, 3040, 2955, 2871, 1620, 1589, 1559, 1489, 1389, 825, 756 cm−1
.
CDCl3): δ = 196.7, 195.4, 156.4, 155.9, 141.1, 138.7, 138.5, 1H NMR (400 MHz, CDCl3): δ = 0.88 (s, 6H, 2CH3), 1.00 (d, J =
137.8, 133.0, 131.8, 130.6, 130.1, 130.0, 129.9, 128.8, 127.6, 5.4 Hz, 6H, 2CH3), 1.94–2.33 (m, 7H), 2.78 (d, J = 16.3 Hz, 1H),
126.2, 123.1, 122.8, 120.5, 115.8, 107.4, 52.0, 50.0, 42.6, 40.7, 5.09 (s, 1H, CH), 6.09–6.12 (m, 1H, ArH), 6.87–7.24 (m, 6H,
33.0, 32.5, 32.2, 30.1, 28.5, 27.9, 26.8, 21.5, 21.1 ppm. HRMS ArH), 7.33 (d, J = 8.5 Hz, 2H, ArH), 7.52–7.58 (m, 2H, ArH),
m/z: calcd for C37H40N2O2 [M]+ 544.3090, found: 544.3078.
7.90 (d, J = 6.4 Hz, 1H, ArH), 10.27 (s, 1H, NH) ppm. 13C NMR
9-(4,4-Dimethyl-6-oxo-2-(m-tolylamino)cyclohex-1-enyl)-3,3- (100 MHz, CDCl3): δ = 197.3, 196.0, 155.8, 155.7, 141.0, 140.0,
dimethyl-10-m-tolyl-3,4,9,10-tetrahydroacridin-1(2H)-one (3ae). 139.2, 135.1, 132.7, 132.1, 131.8, 130.1, 129.6, 129.1, 128.5,
Yellow solid. Mp = 242–244 °C. IR(KBr) ν = 3129, 3063, 3013, 127.6, 126.7, 123.7, 121.5, 115.9, 107.9, 52.3, 50.2, 42.9, 40.9,
2954, 2867, 1636, 1584, 1558, 1495, 1457, 1394, 889, 750, 33.5, 32.7, 32.4, 30.4, 29.0, 27.8, 26.7 ppm. HRMS m/z: calcd
1
727 cm−1. H NMR (400 MHz, CDCl3): δ = 0.90 (d, J = 6.4 Hz, for C35H34Cl2N2O2 [M]+ 584.1997, found: 584.1967.
6H, 2CH3), 1.00 (d, J = 12.3 Hz, 6H, 2CH3), 2.00–2.33 (m, 7H),
10-(3-Chlorophenyl)-9-(2-(3-chlorophenylamino)-4,4-dimethyl-6-
2.39 (s, 3H, CH3), 2.46 (s, 3H, CH3), 2.86 (d, J = 15.2 Hz, 1H), oxocyclohex-1-enyl)-3,3-dimethyl-3,4,9,10-tetrahydroacridin-1(2H)-
5.12 (s, 1H, CH), 6.08–6.13 (m, 1H, ArH), 6.85–6.87 (m, 2H, one (3ai). Yellow solid. Mp = 202–204 °C. IR (KBr) ν = 3156,
ArH), 6.92 (d, J = 7.6 Hz, 1H, ArH), 6.98–7.24 (m, 5H, ArH), 3063, 2955, 2871, 1628, 1582, 1489, 1389, 887, 748, 725 cm−1
.
7.27–7.31 (m, 1H, ArH), 7.40–7.50 (m, 1H, ArH), 7.68–7.72 (m, 1H NMR (400 MHz, CDCl3): δ = 0.89 (s, 6H, 2CH3), 1.02 (d, J =
1H, ArH), 10.21 (s, 1H, NH) ppm. 13C NMR (100 MHz, CDCl3): 8.3 Hz, 6H, 2CH3), 1.94–2.34 (m, 7H), 2.84 (d, J = 16.4 Hz, 1H),
δ = 196.9, 195.8, 156.2, 155.9, 141.5, 141.1, 140.4, 140.3, 139.6, 5.08 (s, 1H, CH), 6.01 (s, 1H, ArH), 6.89–7.07 (m, 5H, ArH),
139.4, 131.1, 129.8, 129.4, 129.1, 128.8, 127.6, 127.4, 126.3, 7.19–7.98 (m, 6H, ArH), 10.33 (s, 1H, NH) ppm. 13C NMR
124.0, 123.3, 121.2, 119.5, 115.8, 107.3, 52.1, 50.1, 42.6, 40.8, (100 MHz, CDCl3): δ = 197.1, 195.9, 155.3, 155.0, 142.6, 141.7,
33.2, 32.6, 32.3, 32.2, 30.2, 28.6, 27.8, 26.9, 21.7 ppm. HRMS 140.6, 136.7, 135.0, 132.2, 131.2, 130.7, 130.3, 129.5, 129.4,
m/z: calcd for C37H40N2O2 [M]+ 544.3090, found: 544.3099.
128.9, 127.2, 126.5, 123.5, 122.8, 121.8, 120.0, 115.6, 107.7,
9-(4,4-Dimethyl-6-oxo-2-(o-tolylamino)cyclohex-1-enyl)-3,3- 52.2, 50.0, 42.6, 40.8, 33.4, 32.6, 32.2, 30.2, 28.9, 27.5,
dimethyl-10-o-tolyl-3,4,9,10-tetrahydroacridin-1(2H)-one (3af). 26.5 ppm. HRMS m/z: calcd for C35H34Cl2N2O2 [M]+ 584.1997,
Yellow solid. Mp = 236–238 °C. IR(KBr) ν = 3142, 3014, 2957, found: 584.1968.
2867, 1640, 1592, 1559, 1486, 1393, 750, 709 cm−1
.
1H NMR
10-(4-Bromophenyl)-9-(2-(4-bromophenylamino)-4,4-dimethyl-6-
(400 MHz, CDCl3): δ = 0.91 (d, J = 10.1 Hz, 6H, 2CH3), 0.98 (d, oxocyclohex-1-enyl)-3,3-dimethyl-3,4,9,10-tetrahydroacridin-
J = 3.0 Hz, 6H, 2CH3), 2.03–2.12 (m, 4H), 2.19 (s, 3H, CH3), 1(2H)-one (3aj). Yellow solid. Mp = 241–243 °C. IR (KBr) ν =
2.26 (s, 3H, CH3), 2.53–2.62 (m, 4H), 5.20 (s, 1H, CH), 3156, 3056, 2955, 2871, 1613, 1589, 1566, 1489, 1389, 825,
1
5.99–6.01 (m, 1H, ArH), 6.86–6.88 (m, 2H, ArH), 7.01–7.10 (m, 756 cm−1. H NMR (400 MHz, CDCl3): δ = 0.88 (s, 6H, 2CH3),
1H, ArH), 7.13 (d, J = 7.1 Hz, 2H, ArH), 7.23 (d, J = 7.3 Hz, 1H, 1.00 (d, J = 5.2 Hz, 6H, 2CH3), 1.94–2.33 (m, 7H), 2.79 (d, J =
ArH), 7.28 (d, J = 7.3 Hz, 1H, ArH), 7.34–7.43 (m, 3H, ArH), 16.3 Hz, 1H), 5.08 (s, 1H, CH), 6.09–6.11 (m, 1H, ArH),
7.85–7.87 (m, 1H, ArH), 9.63 (s, 1H, NH) ppm. 13C NMR 6.87–6.98 (m, 3H, ArH), 7.07 (d, J = 8.4 Hz, 2H, ArH), 7.17 (d,
(100 MHz, CDCl3): δ = 196.5, 195.5, 157.2, 155.4, 139.7, 139.6, J = 6.6 Hz, 1H, ArH), 7.47 (d, J = 8.5 Hz, 2H, ArH), 7.71–7.85
139.4, 137.6, 132.7, 131.9, 131.1, 130.2, 129.1, 128.9, 128.8, (m, 3H, ArH), 10.27 (s, 1H, NH) ppm. 13C NMR (100 MHz,
127.6, 126.7, 126.6, 124.8, 124.6, 123.1, 121.2, 114.9, 107.4, CDCl3): δ = 197.0, 195.7, 155.3, 140.6, 140.4, 140.2, 139.5,
51.8, 50.2, 41.4, 40.9, 32.6, 32.5, 32.2, 32.0, 29.3, 27.8, 27.3, 134.4, 133.5, 132.8, 132.3, 129.0, 128.8, 127.3, 126.8, 126.4,
18.6, 17.7 ppm. HRMS m/z: calcd for C37H40N2O2 [M]+ 123.9, 123.7, 123.4, 122.9, 121.4, 115.7, 111.6, 107.6, 60.5, 52.0,
544.3090, found: 544.3089.
9-(4,4-Dimethyl-6-oxo-2-(phenylamino)cyclohex-1-enyl)-3,3- m/z: calcd for C35H34Br2N2O2 [M]+ 674.0967, found: 674.0970.
dimethyl-10-phenyl-3,4,9,10-tetrahydroacridin-1(2H)-one (3ag). 10-(4-Iodophenyl)-9-(2-(4-iodophenylamino)-4,4-dimethyl-6-
Yellow solid. Mp = 152–154 °C. IR (KBr) ν = 3148, 3033, 2955, oxocyclohex-1-enyl)-3,3-dimethyl-3,4,9,10-tetrahydroacridin-
2871, 1736, 1589, 1559, 1489, 1458, 1389, 748, 702cm−1 1H 1(2H)-one (3ak). Yellow solid. Mp = 264–266 °C. IR (KBr) ν =
49.9, 42.6, 41.7, 40.6, 36.5, 33.2, 32.1, 28.7, 27.5 ppm. HRMS
.
NMR (400 MHz, CDCl3): δ = 0.89 (s, 6H, 2CH3), 0.98 (s, 3H, 3143, 3058, 2953, 2864, 1609, 1583, 1566, 1483, 1389, 824,
1
CH3), 1.02 (s, 3H, CH3), 1.96–2.33 (m, 7H), 2.85 (d, J = 16.4 Hz, 750 cm−1. H NMR (400 MHz, CDCl3): δ = 0.87 (s, 6H, 2CH3),
1H), 5.14 (s, 1H, CH), 6.09–6.11 (m, 1H, ArH), 6.85–7.00 (m, 1.00 (d, J = 4.8 Hz, 6H, 2CH3), 1.94–2.32 (m, 7H), 2.80 (d, J =
3H, ArH), 7.10 (t, J = 7.0 Hz, 1H, ArH), 7.20–7.62 (m, 8H, ArH), 16.7 Hz, 1H), 5.07 (s, 1H, CH), 6.09–6.11 (m, 1H,
7.93 (d, J = 7.3 Hz, 1H, ArH), 10.26 (s, 1H, NH) ppm. 13C NMR ArH), 6.87–6.89 (m, 2H, ArH), 6.95 (d, J = 7.6 Hz, 4H, ArH),
(100 MHz, CDCl3): δ = 196.8, 195.6, 155.9, 155.7, 141.1, 140.4, 7.02–7.04 (m, 1H, ArH), 7.75 (d, J = 7.7 Hz, 2H, ArH), 7.89–
131.2, 130.9, 130.4, 129.4, 129.3, 128.8, 127.4, 126.3, 123.2, 7.93(m, 2H, ArH), 10.29 (s, 1H, NH) ppm. 13C NMR (100 MHz,
123.0, 122.3, 121.1, 115.7, 107.3, 60.54, 52.0, 49.9, 42.6, 40.6, CDCl3): δ = 197.1, 195.9, 155.4, 155.2, 143.5, 141.1, 140.8,
33.1, 32.5, 32.1, 30.0, 27.8, 26.5 ppm. HRMS m/z: calcd for 140.7, 140.3, 138.9, 138.3, 133.1, 132.5, 128.9, 128.5, 127.7,
C35H36N2O2 [M]+ 516.2777, found: 516.2752.
127.5, 127.3, 126.5, 124.0, 123.6, 121.7, 115.8, 107.7, 52.2, 50.0,
10-(4-Chlorophenyl)-9-(2-(4-chlorophenylamino)-4,4-dimethyl-6- 42.8, 41.9, 40.8, 40.3, 33.4, 32.2, 30.2, 28.9, 26.6 ppm.
oxocyclohex-1-enyl)-3,3-dimethyl-3,4,9,10-tetrahydroacridin-1(2H)- HRMS m/z: calcd for C35H34I2N2O2 [M]+ 768.0710, found:
one (3ah). Yellow solid. Mp = 234–236 °C. IR (KBr) ν = 3156, 768.0721.
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10-(4-Methoxyphenyl)-9-(2-(4-methoxyphenylamino)-4,4- 0.98 (d, J = 2.1 Hz, 6H), 2.04–1.95 (m, 3H), 2.06–2.13 (m, 2H),
dimethyl-6-oxocyclohex-1-enyl)-3,3-dimethyl-6-nitro-3,4,9,10- 2.26–2.18 (m, 2H), 2.32 (s, 3H), 2.62 (d, J = 16.3 Hz, 1H), 3.86
tetrahydroacridin-1(2H)-one (3ba). Yellow solid. Mp
231.2–232.6 °C. IR (KBr) ν = 2960, 2929, 1608, 1578, 1509, (dd, J = 9.0, 2.6 Hz, 1H), 6.58 (d, J = 2.6 Hz, 1H), 6.94 (d, J =
1387, 1324, 1262, 1241, 1179, 1033, 830, 802, 761, 735 cm−1
8.8 Hz, 2H), 7.01 (dd, J = 8.5, 2.8 Hz, 1H), 7.06 (dd, J = 8.6,
=
(s, 3H), 3.88 (s, 3H), 4.91 (s, 1H), 6.01 (d, J = 9.0 Hz, 1H), 6.39
.
1H NMR (600 MHz, CDCl3): δ = 0.89 (d, J = 12.1 Hz, 6H), 0.99 2.7 Hz, 1H), 7.10–7.15 (m, 3H), 7.23–7.26 (m, 2H), 7.66 (d, J =
(d, J = 12.5 Hz, 6H), 2.00–2.32 (m, 7H), 2.67 (d, J = 16.6 Hz, 8.3 Hz, 2H), 7.77–7.73 (m, 1H), 9.87 (s, 1H) ppm. 13C NMR
1H), 3.85 (s, 3H), 3.93 (s, 3H), 5.08 (s, 1H), 6.94 (d, J = 8.6 Hz, (75 MHz, CDCl3): δ = 196.9, 195.0, 159.8, 157.7, 156.7, 155.9,
2H), 7.03 (d, J = 1.8 Hz, 1H), 7.13–7.07 (m, 3H), 7.16–7.22 (m, 145.3, 145.2, 140.3, 133.6, 132.8, 131.9, 131.1, 129.8, 129.2,
3H), 7.69–7.72 (m, 1H), 7.80 (d, J = 7.8 Hz, 1H), 10.02 (s, 1H) 128.8, 125.0, 122.3, 119.8, 118.8, 116.3, 116.2, 114.8, 114.7,
ppm. 13C NMR (150 MHz, CDCl3): δ = 197.4, 194.9, 158.3, 107.1, 55.8, 55.7, 51.8, 49.9, 42.5, 40.8, 32.8, 32.4, 32.1,
156.9, 155.8, 146.6, 142.3, 135.2, 133.3, 131.0, 129.2, 125.3, 30.1, 28.7, 27.8, 26.7, 21.8 ppm. HRMS m/z: calcd for
118.6, 117.8, 116.6, 115.3, 114.7, 110.5, 107.7, 55.8, 51.6, 49.9, C44H46N2NaO7S [M + Na]+ 769.2923, found 769.2931.
42.5, 40.7, 32.7, 32.5, 32.1, 30.1, 28.3, 28.1, 26.7 ppm. HRMS
7-(Benzyloxy)-10-(4-methoxyphenyl)-9-(2-(4-methoxyphenyl-
amino)-4,4-dimethyl-6-oxocyclohex-1-enyl)-3,3-dimethyl-3,4,9,10-
m/z: calcd for C37H40N3O6 [M + H]+ 622.2917, found 622.2912.
7-Chloro-10-(4-methoxyphenyl)-9-(2-(4-methoxyphenylamino)- tetrahydroacridin-1(2H)-one (2fa). Yellow solid. Mp
4,4-dimethyl-6-oxocyclohex-1-enyl)-3,3-dimethyl-3,4,9,10-tetra- 194.9–196.7 °C. IR (KBr) ν = 2951, 2866, 1574, 1560, 1509,
hydroacridin-1(2H)-one (3ca). Yellow solid. Mp
1492, 1388, 1242, 1219, 1032, 1010, 831, 805, 755 cm−1 1H
216.1–217.9 °C. IR (KBr) ν = 2953, 1598, 1581, 1555, 1481, NMR (400 MHz, CDCl3): δ = 0.87 (d, J = 10.0 Hz, 6H), 0.97 (s,
1386, 1365, 1270, 1241, 1184, 1027, 833, 811, 607 cm−1 1H 6H), 2.06–2.00 (m, 3H), 2.08–2.14 (m, 2H), 2.17–2.31 (m, 2H),
=
=
.
.
NMR (600 MHz, CDCl3): δ = 0.88 (d, J = 9.3 Hz, 6H), 0.99 (d, J = 2.61 (d, J = 16.3 Hz, 1H), 3.84 (s, 3H), 3.89 (s, 3H), 4.99–4.91
11.9 Hz, 6H), 2.05–1.98 (m, 2H), 2.13 (t, J = 16.6 Hz, 3H), 2.25 (m, 2H), 5.05 (s, 1H), 6.08 (d, J = 8.9 Hz, 1H), 6.50 (dd, J = 8.9,
(dd, J = 37.4, 16.3 Hz, 2H), 2.70 (d, J = 16.4 Hz, 1H), 3.84 (s, 2.9 Hz, 1H), 6.61 (d, J = 2.4 Hz, 1H), 6.92 (d, J = 8.8 Hz, 2H),
3H), 3.90 (s, 3H), 5.02 (s, 1H), 6.07 (d, J = 8.8 Hz, 1H), 7.00–7.18 (m, 5H), 7.38–7.27 (m, 5H), 7.80 (d, J = 7.3 Hz, 1H),
6.78–6.82 (m, 1H), 6.91–6.96 (m, 3H), 7.03 (dd, J = 8.5, 2.8 Hz, 10.07 (s, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.4,
1H), 7.08 (dd, J = 8.6, 2.6 Hz, 1H), 7.20–7.13 (m, 3H), 7.80 (d, 195.1, 159.6, 157.2, 156.4, 156.0, 155.0, 137.6, 135.8, 134.1,
J = 8.5, 1H), 10.04 (s, 1H) ppm. 13C NMR (150 MHz, CDCl3): δ = 133.4, 132.1, 131.2, 129.5, 128.8, 128.0, 127.6, 124.8, 119.3,
196.8, 195.1, 159.7, 157.7, 156.6, 155.8, 140.2, 133.7, 132.8, 116.7, 116.1, 115.3, 114.6, 112.3, 106.5, 70.4, 55.8, 55.7, 51.9,
131.9, 131.1, 129.6, 128.3, 127.9, 126.1, 125.0, 118.9, 116.9, 50.0, 42.6, 40.7, 32.9, 32.7, 32.1, 30.1, 27.9, 26.8 ppm. HRMS
116.2, 114.8, 114.6, 107.4, 55.8, 55.7, 51.8, 49.9, 42.5, 40.8, m/z: calcd for C44H47N2O5 [M + H]+ 683.3485, found 683.3479.
32.9, 32.3, 32.1, 30.2, 28.6, 27.9, 26.7 ppm. HRMS m/z: calcd
9-(5-Methoxy-1H-indol-3-yl)-10-(4-methoxyphenyl)-3,3-dimethyl-
3,4,9,10-tetrahydroacridin-1(2H)-one (5a). Yellow soild. Mp =
for C37H40ClN2O4 [M + H]+ 611.2677, found 611.2671.
7-Fluoro-10-(4-methoxyphenyl)-9-(2-(4-methoxyphenylamino)- 225.1–227.8 °C. IR (KBr) ν = 3283, 2962, 2923, 2867, 1596,
4,4-dimethyl-6-oxocyclohex-1-enyl)-3,3-dimethyl-3,4,9,10-tetra- 1558, 1509, 1484, 1456, 1391, 1268, 1241, 1182, 1023, 850, 749,
1
hydroacridin-1(2H)-one
(3da). Yellow
solid.
Mp
=
634 cm−1. H NMR (400 MHz, CDCl3): δ = 0.78 (s, 3H), 0.95 (s,
219.9–221.8 °C. IR (KBr) ν = 2956, 2866, 1608, 1569, 1508, 3H), 2.05–1.94 (m, 1H), 2.13–2.27 (m, 3H), 3.78 (s, 3H), 3.91 (s,
1490, 1386, 1366, 1243, 1231, 1149, 1032, 825, 808, 779, 3H), 5.70 (s, 1H), 6.32 (d, J = 7.5 Hz, 1H), 6.75 (d, J = 7.0 Hz,
1
605 cm−1. H NMR (400 MHz, CDCl3): δ = 0.88 (d, J = 5.2 Hz, 1H), 6.98–6.90 (m, 3H), 7.07 (d, J = 8.5 Hz, 2H), 7.18–7.11 (m,
6H), 0.99 (d, J = 6.2 Hz, 6H), 2.05–2.00 (m, 2H), 2.17–2.07 (m, 2H), 7.22–7.28 (m, 3H), 7.95 (s, 1H) ppm. 13C NMR (100 MHz,
3H), 2.18–2.32 (m, 2H), 2.68 (d, J = 16.5 Hz, 1H), 3.84 (s, 3H), CDCl3): δ = 195.6, 159.6, 153.7, 152.4, 140.4, 132.4, 131.8,
3.90 (s, 3H), 5.06 (s, 1H), 6.10 (dd, J = 9.0, 4.9 Hz, 1H), 6.55 (td, 131.3, 130.0, 126.9, 126.5, 126.4, 123.8, 122.9, 122.6, 115.6,
J = 8.6, 2.9 Hz, 1H), 6.71 (dd, J = 8.8, 2.5 Hz, 1H), 6.93 (d, J = 115.4, 111.5, 110.1, 102.4, 56.1, 55.6, 50.3, 42.3, 32.1, 31.4,
8.8 Hz, 2H), 7.03 (dd, J = 8.6, 2.7 Hz, 1H), 7.08 (dd, J = 8.6, 29.9, 26.9 ppm. HRMS m/z: calcd for C31H31N2O3 [M + H]+
2.5 Hz, 1H), 7.17 (d, J = 8.6 Hz, 3H), 7.80 (d, J = 7.3 Hz, 1H), 479.2335, found 479.2329.
10.03 (s, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.7,
195.1, 159.7, 157.6, 156.6, 156.0, 137.9, 133.8, 133.1, 132.0, tetrahydroacridin-1(2H)-one (5b). Yellow soild. Mp
9-(5-Methoxy-1H-indol-3-yl)-3,3-dimethyl-10-p-tolyl-3,4,9,10-
=
131.2, 130.0, 125.0, 119.0, 116.9, 116.8, 116.2, 114.8, 114.6, 234.9–236.7 °C. IR (KBr) ν = 3312, 2956, 2832, 1597, 1559,
112.8, 112.6, 106.6, 55.8, 55.7, 51.8, 50.0, 42.6, 40.1, 32.8, 32.6, 1508, 1487, 1457, 1383, 1362, 1266, 1244, 1171, 1061, 1032,
1
32.1, 30.1, 28.5, 28.1, 26.7 ppm. HRMS m/z: calcd for 791, 758, 631, 611 cm−1. H NMR (400 MHz, CDCl3): δ = 0.77
C37H40FN2O4 [M + H]+ 595.2972, Found 595.2960.
(s, 3H), 0.94 (s, 3H), 2.04–1.92 (m, 2H), 2.28–2.13 (m, 3H), 2.48
10-(4-Methoxyphenyl)-9-(2-(4-methoxyphenylamino)-4,4- (s, 3H), 3.78 (s, 3H), 5.70 (s, 1H), 6.32–6.26 (m, 1H), 6.74 (dd,
dimethyl-6-oxocyclohex-1-enyl)-6,6-dimethyl-8-oxo-5,6,7,8,9,10- J = 8.7, 2.1 Hz, 1H), 6.95–6.89 (m, 3H), 7.11 (d, J = 8.7 Hz, 1H),
hexahydroacridin-2-yl 4-methylbenzenesulfonate (3ea). Yellow 7.21–7.17 (m, 3H), 7.28–7.25 (m, 1H), 7.37 (d, J = 7.9 Hz, 2H),
solid. Mp = 144.8–146.4 °C. IR (KBr) ν = 2953, 2868, 1569, 8.05 (s, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 195.6, 153.6,
1559, 1508, 1488, 1374, 1242, 1177, 1146, 1032, 827, 813, 745, 152.2, 140.2, 138.9, 137.1, 131.8, 131.0, 130.0, 130.0, 126.9,
705, 661 cm−1 1H NMR (400 MHz, CDCl3): δ = 0.84 (s, 6H), 126.4, 126.4, 123.8, 122.9, 122.5, 115.7, 111.6, 111.5, 110.0,
.
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102.4, 56.1, 50.3, 42.3, 32.2, 31.5, 29.9, 26.9, 21.3 ppm. HRMS 35.1, 32.4, 30.1, 27.1 ppm. HRMS m/z: calcd for C23H25N2O4
m/z: calcd for C31H31N2O2 [M + H]+ 463.2386, found 463.2374.
7-Chloro-9-(5-methoxy-1H-indol-3-yl)-3,3-dimethyl-10-p-tolyl-
3,4,9,10-tetrahydroacridin-1(2H)-one (5c). Yellow soild. Mp =
232.3–235.1 °C. IR (KBr) ν = 3323, 2956, 2867, 2828, 1622,
1559, 1508, 1477, 1417, 1381, 1264, 1172, 1105, 1059, 1032,
[M + H]+ 393.1814, found 393.1814.
Acknowledgements
828, 816, 656 cm−1 1H NMR (400 MHz, CDCl3): δ = 0.77 (s, We gratefully acknowledge the Natural Science Foundation of
.
3H), 0.94 (s, 3H), 1.95 (d, J = 17.2 Hz, 1H), 2.26–2.11 (m, 3H), China (no. 21172162, 21372174), the Young National Natural
2.48 (s, 3H), 3.81 (s, 3H), 5.63 (s, 1H), 6.20 (d, J = 8.8 Hz, 1H), Science Foundation of China (no. 21202113), the Key Labora-
6.77 (dd, J = 8.8, 2.4 Hz, 1H), 6.87 (dd, J = 8.8, 2.4 Hz, 1H), 6.96 tory of Organic Synthesis of Jiangsu Province (KJS1211), PAPD,
(s, 1H), 7.15 (d, J = 8.8 Hz, 1H), 7.19 (d, J = 2.3 Hz, 2H), 7.21 (d, the Project of Scientific and Technologic Infrastructure of
J = 3.1 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 8.03 (s, 1H) ppm. 13C Suzhou (SZS201207) and Soochow University for financial
NMR (100 MHz, CDCl3): δ = 195.7, 153.9, 152.0, 139.4, 139.0, support.
137.0, 132.0, 131.4, 130.0, 129.9, 128.8, 128.6, 126.5, 126.5,
123.1, 122.2, 117.2, 111.8, 111.7, 109.8, 102.6, 56.4, 50.4, 42.4,
32.4, 31.8, 30.0, 27.0, 21.5 ppm. HRMS m/z: calcd for
Notes and references
C31H29ClN2NaO2 [M + Na]+ 519.1815, found 519.1781.
9-(5-Methoxy-1H-indol-3-yl)-3,3-dimethyl-6-nitro-10-p-tolyl-
3,4,9,10-tetrahydroacridin-1(2H)-one (5d). Yellow soild. Mp =
222.5–223.8 °C. IR (KBr) ν = 3417, 2952, 2869, 1623, 1579,
1520, 1485, 1421, 1376, 1320, 1254, 1219, 1057, 1040, 885, 821,
1 (a) M. R. Grimmett, in Comprehensive Heterocyclic Chemistry
II, ed. A. R. Katritsky and E. F. V. Scriven, Pergamon,
Oxford, 1996, vol. 3, pp. 77–220; (b) Metal-Catalyzed Cross-
Coupling Reactions, ed. A. de Meijere and F. Diederich,
Wiley-VCH, Weinheim, 2nd edn, 2004; (c) J.-P. Corbert and
G. Mignani, Chem. Rev., 2006, 106, 2651; (d) A. K. Yudin
and J. F. Hartwig, Catalyzed Carbon-Heteroatom Bond
Formation, Wiley-VCH, Weinheim, 2010.
2 For general reviews and examples, see: (a) J. P. Wolfe,
S. Wagaw, J.-F. Marcoux and S. L. Buchwald, Acc. Chem.
Res., 1998, 31, 805; (b) J. F. Hartwig, Acc. Chem. Res., 1998,
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1
800, 743, 676, 623 cm−1. H NMR (400 MHz, CDCl3): δ = 0.80
(s, 3H), 0.96 (s, 3H), 1.99 (d, J = 17.3 Hz, 1H), 2.29–2.14 (m,
3H), 2.52 (s, 3H), 3.83 (s, 3H), 5.72 (s, 1H), 6.78 (dd, J = 8.8, 2.4
Hz, 1H), 6.92 (d, J = 2.4 Hz, 1H), 7.16 (dd, J = 5.5, 3.3 Hz, 2H),
7.22 (d, J = 8.3 Hz, 3H), 7.38 (d, J = 8.4 Hz, 1H), 7.44 (d, J =
8.1 Hz, 2H), 7.74 (dd, J = 8.3, 2.2 Hz, 1H), 8.08 (s, 1H) ppm.
13C NMR (100 MHz, CDCl3): δ = 195.9, 154.1, 152.0, 146.9,
140.9, 140.1, 136.2, 134.0, 132.0, 131.8, 130.9, 129.7, 126.2,
123.1, 121.6, 118.5, 112.0, 111.9, 110.8, 110.1, 102.4, 56.4, 50.4,
42.3, 32.4, 31.9, 30.0, 27.0, 21.6 ppm. HRMS m/z: calcd for
C31H29N3NaO4 [M + Na]+ 530.2056, found 530.2031.
7-Chloro-3,3-dimethyl-9-(5-methyl-1H-indol-3-yl)-10-p-tolyl-
3,4,9,10-tetrahydroacridin-1(2H)-one (5e). Yellow soild. Mp =
257.2–260.9 °C. IR (KBr) ν = 3299, 2950, 2922, 2863, 1598,
1559, 1476, 1383, 1360, 1322, 1265, 1178, 1106, 1036, 811, 796,
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.
0.94 (s, 3H), 2.02–1.95 (m, 1H), 2.25–2.08 (m, 3H), 2.43 (s, 3H),
2.50 (s, 3H), 5.60 (s, 1H), 6.15 (d, J = 8.9 Hz, 1H), 6.83 (dd, J =
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2.3 Hz, 1H), 7.17 (d, J = 7.9 Hz, 2H), 7.25 (d, J = 2.8 Hz, 2H),
7.41 (d, J = 8.0 Hz, 2H), 7.49 (s, 1H), 8.10 (s, 1H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 195.7, 151.9, 139.4, 138.7, 137.1,
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C31H29ClN2NaO [M + H]+ 503.1866, Found 503.1846.
3,3-Dimethyl-9-(nitromethyl)-10-(4-nitrophenyl)-3,4,9,10-tetra-
hydroacridin-1(2H)-one (6). Yellow soild. Mp = 240.2–242.9 °C.
1H NMR (400 MHz, CDCl3): δ = 7.25 (dd, J = 6.1, 3.0 Hz, 1H),
7.14 (d, J = 8.2 Hz, 2H), 7.08–7.03 (m, 4H), 6.30–6.25 (m, 1H),
4.91 (t, J = 4.3 Hz, 1H), 4.74 (dd, J = 11.0, 5.0 Hz, 1H), 4.52 (dd,
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2H), 1.03 (s, 3H), 1.00 (s, 3H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 195.4, 159.9, 155.7, 140.9, 131.7, 130.9, 128.9,
128.1, 124.5, 121.9, 116.8, 115.7, 104.0, 81.1, 55.8, 50.2, 42.4,
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