Tandem arylation/friedel-crafts reactions of o-acylanilines with diaryliodonium salts: A modular synthesis of acridine derivatives

Article abstract of DOI:10.1002/ejoc.201500161

A modular method to synthesize acridine derivatives was developed with o-acylanilines and diaryliodonium salts. The reactions proceeded smoothly under Cu-catalyzed or metal-free reaction conditions at elevated temperature through tandem arylation/Friedel-Crafts reactions.

Full text of DOI:10.1002/ejoc.201500161

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DOI: 10.1002/ejoc.201500161
Tandem Arylation/Friedel–Crafts Reactions of o-Acylanilines with
Diaryliodonium Salts: A Modular Synthesis of Acridine Derivatives
Xinlong Pang,[a,b] Zhenbang Lou,[a,b] Ming Li,*[a] Lirong Wen,[a] and Chao Chen*[b]
Keywords: Synthetic methods / Domino reactions / Homogeneous catalysis / Copper / Nitrogen heterocycles
A modular method to synthesize acridine derivatives was free reaction conditions at elevated temperature through
developed with o-acylanilines and diaryliodonium salts. The
tandem arylation/Friedel–Crafts reactions.
reactions proceeded smoothly under Cu-catalyzed or metal-
unusual electronic and photophysical properties.[4] They are
also designed as fascinating catalyst backbones because of
Introduction
Acridine derivatives have attracted considerable interest their rigid structures with dentate nitrogen atoms.[5] Hence,
because of their unique physical and chemical properties, there is high demand to develop synthetic methods for the
biological activities, and industrial applications. Acridine construction of various acridine derivatives for the chemis-
derivatives and analogues have been applied in industry as try community. As one of the earliest practical syntheses of
pigments and dyes for a long time.[1] It is well-known that acridines, the Brenthsen reaction was achieved by heating a
acridine derivatives exhibit a range of biological activities diphenylamine and a carboxylic acid together with ZnCl2
such as antibacterial, antimalarial, antitumor, or intercalat- at 200–270 °C.[6] The cyclization reactions of (2-formyl- or
ing DNA and RNA.[2,3] Acridine derivatives with extended 2-ketophenyl)(phenyl)amines to produce acridines were also
conjugated systems are expected to be promising candidates reported, but the starting materials were not readily avail-
for organic semiconductor materials because they have able. Other methods for the preparation of acridines were
Scheme 1. The modular synthesis of acridine derivatives from diaryliodonium salts and o-acylanilines.
[a] College of Chemistry and Molecular Engineering, Qingdao
University of Science & Technology,
also known and include C–H functionalization, dehydroge-
nation, or metal-catalyzed coupling.[7,8] These known meth-
ods often require either harsh reaction conditions, such as
high temperature, strongly basic or acidic media, or ob-
taining the starting materials is difficult. Therefore, it is
highly desirable to develop new synthetic methods for acri-
dine derivatives under relatively mild conditions. Very re-
cently, we reported a method to prepare 9-aminoacridines
from o-cyanoanilines and diaryliodonium salts (2 equiv.)
Qingdao 266042, P. R. China
E-mail: liming928@qust.edu.cn
[b] Key Laboratory of Bioorganic Phosphorus Chemistry &
Chemical Biology (Ministry of Education), Department of
Chemistry, Tsinghua University,
Beijing 100084, P. R. China
E-mail: Chenchao01@mails.tsinghua.edu.cn
http://www.tsinghua.edu.cn/publish/chemen/2141/2011/
20110530144359091367943/20110530144359091367943_.htmls
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500161.
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X. Pang, Z. Lou, M. Li, L. Wen, C. Chen
FULL PAPER
through double arylation and Friedel–Crafts reactions.[9] 10 mol-%, but in much lower yield when 5 mol-% of CuI
Herein, we report a modular and more general method to was used (Table 1, Entries 3–6). Other CuII salts also cata-
synthesize acridines (and acridones) from readily available lyzed this reaction but gave lower product yields than CuI
o-acylanilines and diaryliodonium salts. The reactions pro- (Table 1, Entries 7–13). As for many cases that use diaryl-
ceeded smoothly under Cu-catalyzed reaction conditions or iodonium salts, the reaction performed best in DCE as
metal-free conditions at elevated temperature by tandem
arylation/Friedel–Crafts[9] reactions (Scheme 1).
Results and Discussion
Diaryliodonium salts, Ar2I+X–, have received much
attention as a result of their powerful arylation ability, even
for many weak nucleophiles to synthesize valuable aryl
compounds.[10,11] Recent findings demonstrated that diaryl-
iodonium salts could be employed as C2 building blocks in
organic reactions, which extended their wider application in
the synthesis of arenes and hetero-arenes.[12] During the
study of synthesizing nitrogen-containing heterocycles with
diaryliodonium salts, we found 9-methyl-acridine[13] 4aa
was formed in 60% yield when diphenyliodonium triflate
(Ph2I+OTf–) 1a was treated with o-acetylaniline 2a at
100 °C in dichloroethane (DCE; see Table 1). The yield of
4aa increased to 75% when the reaction was performed at
130 °C (Table 1, Entries 1 and 2), whereas the addition of
copper salts significantly enhanced the reaction. When
20 mol-% of CuBr was added, 4aa was formed in 92% yield
as determined by NMR spectroscopy. Excitingly, when
20 mol-% of CuI was added, 4aa was formed quantitatively
and isolated in 95% yield. The product was obtained in the
Figure 1. ORTEP drawing of 4ah (C14H11N) with 35% probability
ellipsoids.
same yield when the loading of CuI was decreased to
Table 1. Conditions screened for the formation of 4aa from 1a and
Table 2. Conditions screened for the formation of 5a from 1a and
2a.
2a.
Entry Solvent
Cat. [%]
Temp. [°C] Yield [%][a]
Entry Solvent
Cat. [%]
Temp. [°C] Yield [%][a]
1
2
3
4
5
6
7
8
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCM
THF
–
–
100
130
65
65
65
65
60
65
70
90
65
65
65
65
65
65
65
65
60
75
92
1
2
3
4
5
6
7
8
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
CH3CN
toluene
dioxane
THF
Cu(OTf)2 (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
CuI(10)
CuI (20)
CuBr (20)
CuCl (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
40
65
80
90
29
39
43
54
73
71
83
CuBr(20)
CuI (20)
CuI (10)
99 (95[b]
99 (95[b]
88 (84[b]
75
)
)
)
100
110
120
130
140
130
130
130
130
130
130
130
130
130
CuI (5)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
CuCl2 (20)
CuSO4·H2O (20)
Cu(OAc)2 (20)
CuI (20)
CuI (20)
CuI (20)
CuI (20)
CuI (20)
85
83
85
93
90
64
92
78
92 (87[b]
86
)
9
9
10
11
12
13
14
15
16
17
18
10
11
12
13
14
15
16
17
18
79
11
6
9
9
81
88
83
CH3CN
toluene
dioxane
31
82
73
87
[a] NMR spectroscopic yields with trichloroethylene as internal
standard. [b] Isolated yields.
[a] NMR yields with trichloroethylene as internal standard. [b] Iso-
lated yield.
2
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Modular Synthesis of Acridine Derivatives
solvent (Table 1, Entries 14–18). Optimal conditions for this 4ka. It was pleasant to find that diaryliodonium salts could
reaction are shown in Table 1, Entry 5. accommodate trifluoromethyl group (an electron-with-
After the optimized conditions for the formation of 4aa drawing group 1h), methoxyl group (an electron-donating
were obtained, the reaction was further extended to other group 1l) or poly-substituents (1m–1o) in this reaction to
diaryliodonium triflates (listed in Scheme 2). The reactions give the corresponding acridines.
were performed in the presence of CuI (condition A) and
The above results have proven the generality of diaryl-
thermally (condition B). Under optimal conditions, p, o, or iodonium salts for the synthesis of acridine derivatives.
m-ditolyliodoniums (1b–1d) reacted smoothly with 1a to Next, substituted o-acylaniline derivatives were examined in
produce corresponding products 4ba–4da, all in good the reactions with diaryliodonium salts 1a and 1b. As
yields. Two inseparable isomers were obtained with m-ditol- shown in Scheme 3, substituted o-acetylanilines 1b–1e were
yliodonium (1d) under condition A, but only one isomer also suitable for the reaction to give expected products 4ab–
was formed under condition B. Diaryliodonium salts that 4ae. 2-Aminobenzaldehyde was also able to react with di-
bear a single halogen atom (F, Cl, or Br) were suitable for aryliodonium salts to give corresponding acridines 4af and
the reaction to give expected products 4ea–4ga, and 4ia– 4bf, i.e., acridines without substituents at the 9-position.
Scheme 2. The isolated yields of acridine derivatives 4 from various diaryliodonium salts 1.
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Scheme 3. The isolated yields of acridine derivatives 4 from various o-acylanilines 2.
Furthermore, 2-aminopropiophenone 2g worked well with
Considering the acridone backbone is featured in many
1a to give 9-ethylacridine 4ag. The reactions of 2-amino- dyes, drugs, natural products and organic materials, the
benzophenone 2f with 1a and 1b were accomplished cata- scope of the reaction is worth extending.[16] As shown in
lyzed with CuI to give products 4af and 4bf. The structure Scheme 4, diaryliodonium salts that bear methyl, bromo, or
of 4af was unequivocally confirmed by X-ray diffraction ester group were well suited to the reaction to produce 5b–
analysis (Figure 1).[14]
5d. However, o-aminobenzoates with substituents that in-
After the synthesis of a range of functionalized acridines clude fluoro, chloro, or ester groups also worked with 1a to
was realized with diaryliodonium salts 1 and o-amino- give products 5e–5h in good yields.
phenones 2, we envisaged that this method would be
extended to prepare acridones if o-aminophenones were re-
placed by o-aminobenzoates. When diphenyliodonium tri-
flate 1a was treated with methyl o-aminobenzoate 3a at
Conclusions
40 °C in the presence of Cu(OTf)2 (20%), acridone 5a was
In conclusion, a modular synthesis of acridine derivatives
observed in 39% yield (Table 2).[15] After screening a series was realized with readily available diaryliodonium salts and
of parameters for the reaction, the best condition was deter- o-aminophenones. Moreover, the reaction was successfully
mined as: Cu(OTf)2 (20%) as catalyst and DCE as solvent extended to prepare acridones with o-aminobenzoates in-
at 130 °C. Under these conditions, product 5a was observed stead of o-aminophenones. The facile construction of the
in 92% yield and isolated in 87% yield.
acridine skeleton and simple manipulation might be useful
4
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Modular Synthesis of Acridine Derivatives
Scheme 4. The isolated yields of acridone derivatives 5 from various o-aminobenzoates 3.
General Procedure for Preparing Acridones: A sealed tube was
for design and generation of acridine libraries. Assembling
of other small molecules by means of tandem reactions[17]
to synthesize valuable heterocycles is underway in our labo-
ratory.
charged with a mixture of Cu(OTf)2 (0.2 mmol, 72.0 mg), methyl
2-aminobenzoate derivative 2 (1 mmol), and diaryliodonium salt 1
(1 mmol). The tube was evacuated and recharged with N2 three
times. After DCE (1.5 mL) was added, the tube was sealed and the
mixture was stirred at 130 °C for 12 h. After completion, a solution
of K2CO3 (5 mL, 2n) was added and the mixture was extracted
with ethyl acetate (5 mL ϫ3). The organic phases were combined,
dried with anhydrous Na2SO4, and filtered. Evaporation of the sol-
vent followed by purification with silica gel (petroleum ether/ethyl
acetate/triethylamine, 20:20:1 to 300:100:4) provided the corre-
sponding product.
Experimental Section
General: All the reactions were carried out in a pre-dried screw-
capped tube with a Teflon®-lined septum under a N2 atmosphere.
Substrate Ph2IPF6 was purchased commercially and substituted di-
aryliodonium salts derivatives, except Ph2IPF6, were prepared in
accordance with the literature.[11g,11i,18] Substituted 1-(2-amino-
phenyl)ethanone derivatives were prepared in accordance with the
literature and the ones not listed below were purchased commer-
cially. All solvents were freshly distilled. Column chromatography
was performed with silica gel (particle size 10–40 μm).
9-Methylacridine[8a,8b,13b] (4aa): Light yellow solid; 177.6 mg, yield
92%, m.p. 117–118 °C. 1H NMR (301 MHz, CDCl3): δ = 8.37–8.12
(m, 4 H), 7.76 (ddd, J = 6.5, 3.8, 0.7 Hz, 2 H), 7.63–7.45 (m, 2 H),
3.11 (s, 3 H) ppm. 13C NMR (76 MHz, CDCl3): δ = 148.6 (2ϫ C),
142.3 (2ϫ C), 130.4 (2ϫ CH), 129.8 (2ϫ CH), 125.6 (2ϫ C), 125.5
(2ϫ C), 124.6 (2ϫ CH), 13.7 (2ϫ CH) ppm. HRMS (ESI): m/z
calcd. for C14H11N [M + H]+ 194.0891; found 194.0893. GC–MS:
193.
1H NMR and 13C NMR spectra were recorded with a 300 MHz,
AL-400 MHz, or AL-600 MHz spectrometer at ambient tempera-
ture with CDCl3 or [D6]DMSO as the solvent. The terms m, dq,
q, t, d, and s refer to multiplet, doublet quartet, quartet, triplet,
doublet, and singlet, respectively. Mass spectra were obtained with
an ion trap mass spectrometer. Reaction progress was monitored
by GC if applicable, by using n-dodecane as the internal standard.
Melting points were recorded with a mini-Lamp. MS data were
recorded by ESI-MS.
2,9-Dimethylacridine[8b,13b] (4ba): Yellow solid; 196.7 mg, yield
1
95%, m.p. 89–90 °C. H NMR (400 MHz, CDCl3): δ = 8.18 (d, J
= 8.5 Hz, 2 H), 8.10 (d, J = 8.8 Hz, 1 H), 7.93 (s, 1 H), 7.70 (dd,
J = 8.3, 6.9 Hz, 1 H), 7.57 (d, J = 8.9 Hz, 1 H), 7.53–7.46 (m, 1
H), 6.43 (d, J = 1.5 Hz, 1 H), 3.04 (s, 3 H), 2.57 (s, 3 H) ppm. 13C
NMR (76 MHz, CDCl3): δ = 148.1, 147.5, 141.0, 135.2, 132.7,
130.3, 130.0, 129.3, 125.8, 125.6, 125.4, 124.5, 122.9, 22.3,
13.6 ppm. HRMS (ESI): m/z calcd. for C15H13N [M + H]+
208.1048; found 208.1046. GC–MS: 207.
General Procedure for Preparing Acridines: A sealed tube was
charged with a mixture of CuI (0.1 mmol, 19.0 mg), 1-(2-amino-
phenyl)ethanone derivative 2 (1.0 mmol), and diaryliodonium salt
1 (1.0 mmol). The tube was evacuated and recharged with N2 three
times. After DCE (1.5 mL) was added, the tube was sealed and the
mixture was stirred at 110 °C for 12 h. After completion, a solution
4,9-Dimethylacridine (4ca): Light yellow solid; 186.3 mg, yield 90%,
m.p. 54–55 °C. 1H NMR (400 MHz, CDCl3): δ = 8.26 (d, J =
of K2CO3 (5 mL, 2 n) was added and the mixture was extracted 8.7 Hz, 1 H), 8.20 (d, J = 8.8 Hz, 1 H), 8.07 (d, J = 9.3 Hz, 1 H),
with ethyl acetate (5 mL ϫ3). The organic phases were combined,
dried with anhydrous Na2SO4, and filtered. Evaporation of the sol-
vent followed by purification with silica gel (petroleum ether/ethyl
acetate, 1:1 to 6:1) provided the corresponding product.
7.73 (ddd, J = 8.6, 6.5, 1.3 Hz, 1 H), 7.62–7.57 (m, 1 H), 7.52 (ddd,
J = 8.6, 6.5, 1.2 Hz, 1 H), 7.42 (dd, J = 8.8, 6.7 Hz, 1 H), 3.07 (s,
3 H), 2.95 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 148.1,
147.8, 141.8, 138.0, 131.0, 129.2, 129.1, 125.5, 125.4 (2ϫ CH),
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125.2, 124.4, 122.6, 18.9, 13.8 ppm. HRMS (ESI): m/z calcd. for
4-Bromo-9-methylacridine (4ka): Yellow solid; 201.3 mg, yield 74%,
m.p. 157–158 °C. 1H NMR (301 MHz, CDCl3): δ = 8.35 (d, J =
8.8 Hz, 1 H), 8.30–8.19 (m, 2 H), 8.13 (d, J = 7.2 Hz, 1 H), 7.86–
7.75 (m, 1 H), 7.63–7.52 (m, 1 H), 7.37 (t, J = 8.0 Hz, 1 H), 3.12
(s, 3 H) ppm. 13C NMR (76 MHz, CDCl3): δ = 148.8, 145.1, 143.2,
133.3, 131.1, 130.2, 126.5, 126.3, 126.0, 125.9, 125.3, 124.7, 124.5,
14.1 ppm. HRMS (ESI): m/z calcd. for C14H10BrN [M + H]+
271.9997; found 271.9989. GC–MS: 270.
C15H13N [M + H]+ 208.1048; found 208.1046. GC–MS: 207.
3,9-Dimethylacridine[8a] (4da): Yellow solid; 161.5 mg, yield 78%,
m.p. 73–74 °C, 1H NMR (400 MHz, CDCl3): δ = 8.22 (d, J =
8.5 Hz, 1 H), 8.19 (d, J = 8.7 Hz, 1 H), 8.13 (d, J = 8.9 Hz, 1 H),
7.98 (s, 1 H), 7.76–7.70 (m, 1 H), 7.51 (ddd, J = 8.4, 6.5, 1.1 Hz, 1
H), 7.38 (dd, J = 8.9, 1.6 Hz, 1 H), 3.09 (s, 3 H), 2.59 (s, 3 H) ppm.
13C NMR (101 MHz, CDCl3): δ = 148.7, 137.6, 134.6 (2ϫ C),
134.0, 132.6, 130.0 (2ϫ CH), 123.9 (2ϫ CH), 118.7, 116.1, 114.1,
28.2, 21.0 ppm. HRMS (ESI): m/z calcd. for C15H13N [M + H]+
208.1048; found 208.1046. GC–MS: 207.
4-Methoxy-9-methylacridine (4la): Yellow oil; 182.9 mg, yield 82%.
1H NMR (301 MHz, CDCl3): δ = 8.37 (d, J = 8.7 Hz, 1 H), 8.19
(d, J = 8.7 Hz, 1 H), 7.77 (dd, J = 9.0, 0.8 Hz, 1 H), 7.74–7.68 (m,
1 H), 7.61–7.48 (m, 1 H), 7.42 (dd, J = 8.8, 7.6 Hz, 1 H), 7.00 (d,
J = 7.4 Hz, 1 H), 4.13 (s, 3 H), 3.05 (s, 3 H) ppm. 13C NMR
(76 MHz, CDCl3): δ = 155.6, 147.5, 142.1, 141.7, 131.2, 129.4,
126.6, 125.9, 125.9, 125.3, 124.3, 116.5, 106.1, 56.3, 14.1 ppm.
HRMS (ESI): m/z calcd. for C15H13NO [M + H]+ 224.0997; found
224.0989. GC–MS: 223.
2-Fluoro-9-methylacridine (4ea): Yellow solid; 143.5 mg, yield 68%,
1
m.p. 123–124 °C. H NMR (400 MHz, CDCl3): δ = 8.29–8.06 (m,
3 H), 7.74 (ddd, J = 12.3, 8.2, 1.9 Hz, 2 H), 7.60–7.49 (m, 2 H),
3.00 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 159.8 (d, J
= 248.4 Hz), 148.0, 145.9, 141.4, 133.1 (d, J = 9.0 Hz), 130.4, 129.7,
126.1, 125.8 (d, J = 9.0 Hz), 125.6, 124.3, 121.4 (d, J = 27.9 Hz),
106.8 (d, J = 22.4 Hz), 13.9 ppm. HRMS (ESI): m/z calcd. for
C14H10FN [M + H]+ 212.0797; found 212.0791. GC–MS: 211.
2,4,9-Trimethylacridine (4ma): Yellow solid; 181.2 mg, yield 82%,
m.p. 92–93 °C. 1H NMR (301 MHz, CDCl3): δ = 8.25 (d, J =
8.7 Hz, 1 H), 8.16 (d, J = 8.8 Hz, 1 H), 7.77 (s, 1 H), 7.74–7.67 (m,
1 H), 7.50 (ddd, J = 8.6, 6.6, 1.2 Hz, 1 H), 7.43 (s, 1 H), 3.00 (s, 3
H), 2.92 (s, 3 H), 2.54 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3):
δ = 147.2, 146.9, 140.5, 137.4, 134.7, 132.1, 130.9, 128.8, 125.5,
125.5, 125.2, 124.4, 120.8, 22.4, 18.7, 13.7 ppm. HRMS (ESI): m/z
calcd. for C16H15N [M + H]+ 222.1204; found 222.1208. GC–MS:
221.
2-Chloro-9-methylacridine (4fa): Yellow solid; 161.2 mg, yield 71%,
1
m.p. 143–144 °C. H NMR (400 MHz, CDCl3): δ = 8.16 (s, 1 H),
8.13 (d, J = 2.6 Hz, 2 H), 8.10 (d, J = 9.2 Hz, 1 H), 7.78–7.70 (m,
1 H), 7.63 (dd, J = 9.2, 2.2 Hz, 1 H), 7.55–7.49 (m, 1 H), 2.99 (s,
3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 148.5, 146.7, 141.4,
132.0, 131.4, 130.9, 130.4, 130.1, 126.1, 125.8, 125.8, 124.5, 123.2,
13.7 ppm. HRMS (ESI): m/z calcd. for C14H10ClN [M + H]+
228.0502; found 228.0511. GC–MS: 227.
1,4,9-Trimethylacridine (4na): Yellow solid; 168.1 mg, yield 76%,
m.p. 95–96 °C. 1H NMR (400 MHz, CDCl3): δ = 8.24 (d, J =
8.8 Hz, 1 H), 8.20 (d, J = 8.7 Hz, 1 H), 7.71 (dd, J = 11.1, 4.0 Hz,
1 H), 7.55–7.46 (m, 1 H), 7.42 (d, J = 6.9 Hz, 1 H), 7.18 (d, J =
6.9 Hz, 1 H), 3.26 (s, 3 H), 2.94 (s, 3 H), 2.86 (s, 3 H) ppm. 13C
NMR (101 MHz, CDCl3): δ = 149.3, 147.0, 143.0, 136.1, 133.2,
130.6, 129.1, 128.6, 128.5, 126.9, 126.6, 125.4, 124.3, 26.9, 19.2,
19.0 ppm. HRMS (ESI): m/z calcd. for C16H15N [M + H]+
222.1204; found 222.1208. GC–MS: 221.
2-Bromo-9-methylacridine (4ga): Yellow solid; 193.1 mg, yield 71%,
1
m.p. 152–153 °C. H NMR (301 MHz, CDCl3): δ = 8.25 (s, 1 H),
8.10 (dd, J = 10.6, 9.5 Hz, 2 H), 7.99 (d, J = 9.2 Hz, 1 H), 7.72
(ddd, J = 7.6, 4.4, 1.7 Hz, 2 H), 7.51–7.45 (m, 1 H), 2.91 (s, 3
H) ppm. 13C NMR (76 MHz, CDCl3): δ = 148.5, 146.7, 141.3,
133.2, 132.0, 130.4, 130.1, 126.7, 126.3, 126.1, 125.6, 124.5, 119.7,
13.7 ppm. HRMS (ESI): m/z calcd. for C14H10BrN [M + H]+
271.9997; found 271.9989. GC–MS: 270.
7-Methylbenzo[c]acridine (4oa): Yellow solid; 204.1 mg, yield 84%,
1
9-Methyl-2-(trifluoromethyl)acridine (4ha): Yellow solid; 187.9 mg,
yield 72%, m.p. 120–121 °C. 1H NMR (400 MHz, CDCl3): δ = 8.51
(s, 1 H), 8.27 (d, J = 9.1 Hz, 1 H), 8.23–8.17 (m, 2 H), 7.85 (dd, J
= 9.1, 1.8 Hz, 1 H), 7.80 (ddd, J = 8.8, 6.5, 1.2 Hz, 1 H), 7.56 (ddd,
J = 8.7, 6.6, 1.1 Hz, 1 H), 3.10 (s, 3 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 149.6, 148.7, 144.3, 131.8, 131.0, 130.5, 126.4 (d, J =
149.5 Hz), 126.3, 125.0 (d, J = 192.1 Hz), 124.9, 124.8, 124.7, 123.1
(d, J = 6.8 Hz), 13.8 ppm. HRMS (ESI): m/z calcd. for C15H10F3N
[M + H]+ 262.0765; found 262.0769. GC–MS: 261.
m.p. 126–127 °C. H NMR (301 MHz, CDCl3): δ = 9.56 (dd, J =
7.8, 0.9 Hz, 1 H), 8.46–8.25 (m, 1 H), 8.24–8.09 (m, 1 H), 7.89 (d,
J = 9.4 Hz, 1 H), 7.85–7.69 (m, 4 H), 7.64–7.58 (m, 1 H), 7.58–
7.53 (m, 1 H), 2.96 (s, 3 H) ppm. 13C NMR (76 MHz, CDCl3): δ
= 147.1, 147.1, 140.9, 133.6, 132.2, 130.7, 129.2, 128.9, 127.7, 127.3,
127.1, 126.3, 125.7 (2ϫ CH), 124.3, 123.5, 122.2, 13.7 ppm. HRMS
(ESI): m/z calcd. for C18H13N [M + H]+ 244.1048; found 244.1051.
GC–MS: 243.
2-Bromo-9-methylacridine (4ab): Yellow solid; 192.4 mg, yield 71%,
m.p. 135–136 °C. 1H NMR (400 MHz, CDCl3): δ = 8.38 (d, J =
2.0 Hz, 1 H), 8.19 (dd, J = 15.6, 8.7 Hz, 2 H), 8.06 (d, J = 9.2 Hz,
1 H), 7.81–7.74 (m, 2 H), 7.58–7.53 (m, 1 H), 3.04 (s, 3 H) ppm.
13C NMR (101 MHz, CDCl3): δ = 148.7, 146.8, 141.5, 133.3, 132.1,
130.4, 130.2, 126.8, 126.5, 126.2, 125.8, 124.6, 119.8, 13.8 ppm.
HRMS (ESI): m/z calcd. for C14H10BrN [M + H]+ 271.9997; found
271.9989. GC–MS: 270.
4-Fluoro-9-methylacridine (4ia): Yellow solid; 162.5 mg, yield 77%,
m.p. 123–124 °C. 1H NMR (301 MHz, CDCl3): δ = 8.33 (d, J =
8.8 Hz, 1 H), 8.23 (d, J = 8.9 Hz, 1 H), 8.05–7.97 (m, 1 H), 7.84–
7.72 (m, 1 H), 7.63–7.55 (m, 1 H), 7.45 (dd, J = 8.6, 5.5 Hz, 2 H),
3.11 (s, 3 H) ppm. 13C NMR (76 MHz, CDCl3): δ = 158.2 (d, J =
257.0 Hz), 148.1, 142.5, 139.6 (d, J = 12.1 Hz), 130.8, 130.2, 126.9,
126.1, 125.8, 124.5, 124.4, 124.3, 120.5 (d, J = 5.0 Hz), 112.3 (d, J
= 19.1 Hz), 14.1 ppm. HRMS (ESI): m/z calcd. for C14H10FN [M
+ H]+ 212.0797; found 212.0792. GC–MS: 211.
2-Bromo-7,9-dimethylacridine (4bb): Yellow solid; 230.9 mg, yield
1
81%, m.p. 140–141 °C. H NMR (400 MHz, CDCl3): δ = 8.34 (d,
J = 2.1 Hz, 1 H), 8.04 (dd, J = 13.0, 9.0 Hz, 2 H), 7.91 (s, 1 H),
7.74 (dd, J = 9.2, 2.0 Hz, 1 H), 7.59 (dd, J = 8.9, 1.7 Hz, 1 H), 2.99
(s, 3 H), 2.59 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ =
147.6, 146.3, 140.1, 136.0, 133.1, 132.8, 132.0, 130.1, 126.7, 126.6,
125.8, 122.8, 119.6, 22.3, 13.7 ppm. HRMS (ESI): m/z calcd. for
C15H12BrN [M + H]+ 286.0153; found 286.0157. GC–MS: 285.
4-Chloro-9-methylacridine (4ja): Yellow solid; 183.9 mg, yield 81%,
m.p. 148–149 °C. H NMR (400 MHz, CDCl3): δ = 8.33–8.26 (m,
1 H), 8.09 (ddd, J = 28.0, 8.3, 0.9 Hz, 2 H), 7.83 (d, J = 7.2 Hz, 1
H), 7.79–7.70 (m, 1 H), 7.56–7.47 (m, 1 H), 7.34 (t, J = 8.0 Hz, 1
H), 3.00 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 148.5,
144.5, 143.2, 134.0, 131.0, 130.2, 129.4, 126.4, 126.2, 125.7, 124.7,
1
124.4, 123.9, 14.1 ppm. HRMS (ESI): m/z calcd. for C14H10ClN 9-Methyl-2-phenylacridine (4ca): Light yellow solid; 239.4 mg, yield
1
[M + H]+ 228.0502; found 228.0511. GC–MS: 227.
89%, m.p. 155–156 °C. H NMR (301 MHz, CDCl3): δ = 8.40 (d,
6
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Modular Synthesis of Acridine Derivatives
J = 1.8 Hz, 1 H), 8.26 (dd, J = 18.9, 8.6 Hz, 3 H), 8.05 (dd, J =
9.0, 1.8 Hz, 1 H), 7.79 (d, J = 7.5 Hz, 3 H), 7.55 (dd, J = 15.6,
8.1 Hz, 3 H), 7.44 (d, J = 7.2 Hz, 1 H), 3.16 (s, 3 H) ppm. 13C
NMR (76 MHz, CDCl3): δ = 148.6, 148.0, 142.4, 140.9, 138.1,
17.2, 8.8 Hz, 4 H), 7.81–7.67 (m, 2 H), 7.50 (ddd, J = 8.3, 6.6,
1.0 Hz, 2 H), 3.57 (q, J = 7.7 Hz, 2 H), 1.41 (t, J = 7.7 Hz, 3
H) ppm. 13C NMR (101 MHz, CDCl3): δ = 148.67, 148.55, 130.27,
129.94, 125.66, 124.54, 124.25, 20.91, 15.56 ppm. HRMS (ESI): m/z
130.9, 130.4, 130.1, 129.8, 129.1 (2ϫ CH), 127.8, 127.6 (2ϫ CH), calcd. for C14H11N [M + H]+ 208.1048; found 208.1053. GC–MS:
125.9, 125.7, 125.7, 124.6, 122.2, 13.8 ppm. HRMS (ESI): m/z
calcd. for C20H15N [M + H]+ 270.1204; found 270.1207. GC–MS:
269.
207.
9-Ethyl-2-methylacridine (4bg): Light yellow solid; 201.1 mg, yield
91%, m.p. 106–107 °C. H NMR (400 MHz, CDCl3): δ = 8.18 (d,
1
J = 8.7 Hz, 1 H), 8.09 (dd, J = 8.8, 2.5 Hz, 2 H), 7.84 (s, 1 H), 7.66
(dd, J = 8.0, 7.2 Hz, 1 H), 7.51 (d, J = 8.8 Hz, 1 H), 7.43 (dd, J =
8.0, 7.3 Hz, 1 H), 3.45 (q, J = 7.6 Hz, 2 H), 2.50 (s, 3 H), 1.35 (t,
J = 7.6 Hz, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 148.19,
147.64, 147.17, 135.30, 132.70, 130.36, 130.08, 129.35, 125.50,
124.66, 124.54, 124.18, 122.40, 22.35, 20.76, 15.48 ppm. HRMS
(ESI): m/z calcd. for C14H11N [M + H]+ 208.1048; found 208.1053.
GC–MS: 207.
9-Phenylacridine[19] (4ah): Light yellow solid; 193.8 mg, yield 76%,
m.p. 184–185 °C. 1H NMR (301 MHz, CDCl3): δ = 8.30 (d, J =
8.8 Hz, 2 H), 7.84–7.75 (m, 2 H), 7.74–7.72 (m, 1 H), 7.70 (s, 1 H),
7.59 (dd, J = 4.9, 2.4 Hz, 2 H), 7.47–7.43 (m, 2 H), 7.41 (ddd, J =
7.8, 4.6, 1.6 Hz, 3 H) ppm. 13C NMR (76 MHz, CDCl3): δ = 149.76
(2ϫ C), 148.08, 136.90, 131.4 (2ϫ CH), 130.9 (2ϫ CH), 130.6 (2ϫ
CH), 129.4 (2ϫ CH), 129.3, 127.8 (2ϫ CH), 126.5 (2ϫ CH), 126.1
(2ϫ C) ppm. HRMS (ESI): m/z calcd. for C19H13N [M + H]+
256.1048; found 256.1053. GC–MS: 255.
9-Methyl-2-phenylacridine (4bc): Light yellow solid; 229.2 mg, yield
81%, m.p. 162–163 °C. H NMR (400 MHz, CDCl3): δ = 8.29 (d,
1
J = 1.7 Hz, 1 H), 8.23 (d, J = 9.0 Hz, 1 H), 8.09 (d, J = 8.8 Hz, 1
H), 7.97 (dd, J = 9.1, 1.8 Hz, 1 H), 7.88 (s, 1 H), 7.78–7.71 (m, 2
H), 7.55 (dd, J = 8.8, 1.4 Hz, 1 H), 7.50 (t, J = 7.6 Hz, 2 H), 7.40
(t, J = 7.3 Hz, 1 H), 3.02 (s, 3 H), 2.55 (s, 3 H) ppm. 13C NMR
(101 MHz, CDCl3): δ = 147.4, 141.0, 141.0, 137.8, 135.3, 132.6,
130.8, 130.0, 129.4, 129.1 (2ϫ CH), 127.7, 127.6 (2ϫ CH), 125.8,
125.7, 122.8, 122.1, 22.3, 13.6 ppm. HRMS (ESI): m/z calcd. for
C21H17N [M + H]+ 284.1361; found 284.1357. GC–MS: 283.
10-Methyl-[1,3]dioxolo[4,5-b]acridine (4ad): Yellow solid; 199.1 mg,
yield 84%, m.p. 151–152 °C. 1H NMR (400 MHz, CDCl3): δ = 8.08
(d, J = 8.7 Hz, 2 H), 7.69–7.62 (m, 1 H), 7.45 (ddd, J = 8.4, 6.6,
1.2 Hz, 1 H), 7.36 (s, 1 H), 7.30 (s, 1 H), 6.07 (s, 2 H), 2.88 (s, 3
H) ppm. 13C NMR (101 MHz, CDCl3): δ = 151.56, 147.94, 147.74,
147.07, 139.65, 129.58, 128.79, 124.89, 124.82, 124.10, 123.11,
104.70, 101.82, 98.54, 14.02 ppm. HRMS (ESI): m/z calcd. for
C15H11NO2 [M + H]+ 238.0790; found 238.0783. GC–MS: 237.
X-ray Crystal Structure Analysis of Compound 4ah: Single crystals
suitable for X-ray analysis were obtained by slow evaporation from
a solution of chloroform-cyclohexane. CCDC number: 1042187. Z
= 4, monoclinic, space group P21/n, λ = 0.71073 Å, T = 173 K.
Theta (max) = 27.490°, R (reflections) = 0.0483(2934), wR2 (reflec-
tions) = 0.1202(2983). Formula: C14H11N, M = 255.1048, yellow
crystal, 0.51ϫ0.23ϫ0.06 mm, a = 8.4813 (17), b = 17.802 (4), c =
9.0789 (18) Å, α = 90.00°, β = 107.32(3)°, γ = 90.00°, V =
1308.6(5) Å3, ρ = 1.296 gcm–3, μ = 0.075 mm–1.
8,10-Dimethyl-[1,3]dioxolo[4,5-b]acridine (4bd): Yellow solid;
199.1 mg, yield 70%, m.p. 159–160 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.97 (d, J = 8.8 Hz, 1 H), 7.80 (s, 1 H), 7.48 (d, J =
8.8 Hz, 1 H), 7.34 (s, 1 H), 7.28 (s, 1 H), 6.05 (s, 2 H), 2.83 (s, 3
H), 2.53 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 151.13,
147.83, 147.10, 145.88, 138.55, 134.47, 131.42, 129.28, 124.78,
123.14, 122.54, 104.72, 101.72, 98.53, 22.18, 13.91 ppm. HRMS
(ESI): m/z calcd. for C16H13NO2 [M + H]+ 252.0946; found
252.0946. GC–MS: 251.
2-Methyl-9-phenylacridine (4bh): Yellow solid; 223.3 mg, yield 83%,
m.p. 135–136 °C. 1H NMR (400 MHz, CDCl3): δ = 8.30 (d, J =
8.7 Hz, 1 H), 8.22 (d, J = 8.9 Hz, 1 H), 7.79–7.73 (m, 1 H), 7.70
(d, J = 8.6 Hz, 1 H), 7.67–7.58 (m, 4 H), 7.46 (dd, J = 7.4, 1.8 Hz,
3 H), 7.44–7.38 (m, 1 H), 2.48 (s, 3 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 149.89, 149.43, 147.56, 137.81, 137.05, 134.47, 132.07
(2ϫ CH), 131.22, 131.05, 130.99, 130.06 (2ϫ CH), 129.84, 128.35,
127.08, 126.91, 126.75, 126.37, 23.64 ppm. HRMS (ESI): m/z calcd.
for C20H15N [M + H]+ 270.1204; found 270.1211. GC–MS: 269.
2,4-Dibromo-9-methylacridine (4ae): Yellow solid; 286.2 mg, yield
82%, m.p. 165–166 °C. 1H NMR (400 MHz, CDCl3): δ = 8.24 (dd,
J = 13.1, 5.3 Hz, 2 H), 8.15–8.02 (m, 2 H), 7.74 (t, J = 7.4 Hz, 1
H), 7.55–7.46 (m, 1 H), 2.95 (s, 3 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 168.1, 148.4, 143.2, 142.7, 136.0, 130.7, 126.9, 126.7,
126.6, 126.5, 125.8, 124.4, 118.4, 14.2 ppm. HRMS (ESI): m/z
calcd. for C14H9Br2N [M + H]+ 349.9102; found 349.9105. GC–
MS: 348.
Acridin-9(10H)-one[20,21](5a): Light yellow solid; 146.3 mg, yield
75%, m.p. 250–251 °C. 1H NMR (301 MHz, [D6]DMSO): δ =
11.70 (s, 1 H), 8.34–8.01 (m, 2 H), 7.70 (ddd, J = 8.4, 7.0, 1.6 Hz,
2 H), 7.51 (d, J = 8.4 Hz, 2 H), 7.22 (ddd, J = 8.0, 7.0, 1.0 Hz, 2
H) ppm. 13C NMR (76 MHz, [D6]DMSO): δ = 177.3, 141.4 (2ϫ
C), 134.0 (2ϫ CH), 126.6 (2ϫ CH), 121.6 (2ϫ CH), 121.0 (2ϫ
Acridine[8b] (4af): Yellow solid; 199.1 mg, yield 70%, m.p. 108–
109 °C. H NMR (400 MHz, CDCl3): δ = 8.73 (s, 1 H), 8.23 (d, J
= 8.7 Hz, 2 H), 7.97 (d, J = 8.3 Hz, 2 H), 7.82–7.72 (m, 2 H), 7.51
(t, J = 7.4 Hz, 2 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 149.1,
136.2 (2ϫ C), 130.5 (2ϫ CH), 129.4 (2ϫ CH), 128.3 (2ϫ CH),
126.7 (2ϫ C), 125.8 (2ϫ CH) ppm. HRMS (ESI): m/z calcd. for
C13H9N [M + H]+ 180.0735; found 180.0729. GC–MS: 179.
1
C), 117.9 (2ϫ CH) ppm. IR: ν = 3270 (m), 2989 (s), 1731 (m), 1630
˜
(s), 1527 (s), 866 (s), 855 (m), 746 (vs.) cm–1. HRMS (ESI): m/z
2-Methylacridine[8b] (4bf): Yellow solid; 199.1 mg, yield 70%, m.p.
calcd. for C13H9NO [M + H]+ 196.0684; found 196.0691.
1
134–135 °C. H NMR (400 MHz, CDCl3): δ = 8.54 (s, 1 H), 8.19
2-Methylacridin-9(10H)-one[20,21](5b): Light yellow solid; 181.8 mg,
(d, J = 8.8 Hz, 1 H), 8.11 (d, J = 8.9 Hz, 1 H), 7.90 (d, J = 8.4 Hz,
1 H), 7.70 (ddd, J = 27.3, 14.1, 10.8 Hz, 2 H), 7.57 (dd, J = 8.9,
1.8 Hz, 1 H), 7.52–7.40 (m, 1 H), 2.51 (s, 3 H) ppm. 13C NMR
(101 MHz, CDCl3): δ = 148.60, 148.10, 135.50, 134.96, 133.33,
129.86, 129.43, 129.10, 128.18, 126.76, 126.75, 126.29, 125.60,
21.87 ppm. HRMS (ESI): m/z calcd. for C14H11N [M + H]+
194.0891; found 194.0886. GC–MS: 193.
1
yield 87%, m.p. 341–342 °C. H NMR (400 MHz, [D6]DMSO): δ
= 11.62 (s, 1 H), 8.18 (d, J = 8.1 Hz, 1 H), 7.98 (s, 1 H), 7.65 (dd,
J = 7.9, 7.3 Hz, 1 H), 7.50 (dd, J = 15.3, 5.0 Hz, 2 H), 7.41 (d, J
= 8.5 Hz, 1 H), 7.18 (t, J = 7.5 Hz, 1 H), 2.36 (s, 3 H) ppm. 13C
NMR (101 MHz, [D6]DMSO): δ = 177.09, 141.31, 139.51, 135.43,
133.74, 130.61, 126.55, 125.60, 121.24, 120.90 (2ϫ C), 117.83,
117.78, 21.12 ppm. IR: ν = 3270 (m), 2922 (s), 1731 (m), 1632 (s),
˜
9-Ethylacridine[13b] (4ag): Light yellow solid; 184.3 mg, yield 89%,
1522 (s), 1472 (vs.), 1209 (s), 816 (m), 749 (vs.) cm–1. HRMS (ESI):
m.p. 108–109 °C. H NMR (400 MHz, CDCl3): δ = 8.21 (dd, J = m/z calcd. for C14H11NO [M + H]+ 210.0841; found 210.0837.
1
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Job/Unit: O50161
/KAP1
Date: 08-04-15 15:01:04
Pages: 10
X. Pang, Z. Lou, M. Li, L. Wen, C. Chen
FULL PAPER
2-Bromoacridin-9(10H)-one (5c): Light yellow solid; 212.2 mg, yield
78%, m.p. 376–377 °C. 1H NMR (400 MHz, [D6]DMSO): δ =
11.84 (s, 1 H), 8.23 (d, J = 2.2 Hz, 1 H), 8.16 (d, J = 8.0 Hz, 1 H),
7.77 (dd, J = 8.8, 2.3 Hz, 1 H), 7.69 (dd, J = 11.2, 4.1 Hz, 1 H),
7.46 (dd, J = 11.0, 8.8 Hz, 2 H), 7.22 (dd, J = 12.7, 5.1 Hz, 1
H) ppm. 13C NMR (101 MHz, [D6]DMSO): δ = 176.13, 141.25,
140.21, 136.45, 134.32, 128.45, 126.53, 122.25, 122.01, 120.88,
(vs.), 1467 (vs.), 1260 (s), 1024 (m), 816 (s), 746 (s) cm–1. HRMS
(ESI): m/z calcd. for C15H11NO3 [M + H]+ 254.0739; found
254.0739.
Acknowledgments
This work was supported by National Natural Science Foundation
of China (NSFC) (grant numbers 21102080, 21372138, 21372137,
21072110), the Natural Science Foundation of Shandong Province
(grant numbers ZR2012BM003 and ZR2014BM006), and
Tsinghua University Initiative Scientific Research Program (grant
number 2011Z02150).
120.51, 118.07, 113.62 ppm. IR: ν = 3276 (m), 2946 (m), 1733 (m),
˜
1635 (s), 1555 (s), 1470 (s), 1273 (s), 1024 (vs.), 822 (m), 755 (s),
688 (m) cm–1. HRMS (ESI): m/z calcd. for C14H11NO [M + H]+
273.9789; found 273.9781.
Methyl 9-Oxo-9,10-dihydroacridine-2-carboxylate (5d): Yellow so-
lid; 225.2 mg, yield 89%, m.p. 367–368 °C. 1H NMR (400 MHz,
[D6]DMSO): δ = 11.99 (s, 1 H), 8.75 (d, J = 1.7 Hz, 1 H), 8.17 (d,
J = 7.9 Hz, 1 H), 8.11 (dd, J = 8.7, 1.9 Hz, 1 H), 7.71 (dd, J =
11.2, 4.0 Hz, 1 H), 7.51 (t, J = 7.9 Hz, 2 H), 7.26 (t, J = 7.5 Hz, 1
H), 3.83 (s, 3 H) ppm. 13C NMR (101 MHz, [D6]DMSO): δ =
177.20, 166.26, 144.13, 141.23, 134.55, 133.46, 129.16, 126.59,
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122.54, 122.23, 121.39, 120.12, 118.36, 118.20, 52.61 ppm. IR: ν =
˜
3270 (m), 2917 (s), 2850 (s), 2250 (m), 1725 (m), 1660 (s), 1468 (m),
1294 (m), 1024 (vs.), 821 (s), 759 (s) cm–1. HRMS (ESI): m/z calcd.
for C15H11NO3 [M + H]+ 254.0739; found 254.0739.
2-Fluoroacridin-9(10H)-one (5e): Yellow solid; 220.8 mg, yield 96%,
1
m.p. 365–366 °C. H NMR (400 MHz, [D6]DMSO): δ = 11.71 (s,
1 H), 8.24–8.18 (m, 1 H), 8.15 (d, J = 8.0 Hz, 1 H), 7.64 (dd, J =
8.1, 7.0 Hz, 1 H), 7.42 (d, J = 8.3 Hz, 1 H), 7.19 (t, J = 7.5 Hz, 1
H), 7.13 (d, J = 10.4 Hz, 1 H), 6.98 (dd, J = 12.4, 4.9 Hz, 1 H) ppm.
13C NMR (101 MHz, [D6]DMSO): δ = 176.52, 165.55 (d, J =
249.5 Hz), 142.90 (d, J = 12.9 Hz), 141.49, 134.01, 130.0 (d, J =
11.3 Hz), 126.51, 121.89, 121.04, 118.14, 117.72, 110.4 (d, J =
23.6 Hz), 102.7 (d, J = 24.9 Hz) ppm. IR: ν = 3263 (m), 3095 (m),
˜
2980 (s), 2251 (m), 1723 (m), 1627 (m), 1569 (s), 1463 (s), 1262 (m),
1023 (vs.), 822 (s), 753 (vs.), 666 (m) cm–1. HRMS (ESI): m/z calcd.
for C13H8FNO [M + H]+ 214.0590; found 214.0587.
3-Chloroacridin-9(10H)-one (5f): Yellow solid; 203.8 mg, yield 89%,
1
m.p. 383–384 °C. H NMR (400 MHz, [D6]DMSO): δ = 11.89 (s,
1 H), 8.18 (d, J = 8.1 Hz, 1 H), 8.10 (d, J = 2.3 Hz, 1 H), 7.75–
7.69 (m, 2 H), 7.54 (d, J = 8.9 Hz, 1 H), 7.51 (d, J = 8.3 Hz, 1 H),
7.24 (t, J = 7.5 Hz, 1 H) ppm. 13C NMR (101 MHz, [D6]DMSO):
δ = 176.28, 141.28, 139.99, 134.40, 134.01, 126.53, 125.91, 125.27,
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122.07, 121.76, 120.81, 120.37, 118.08 ppm. IR: ν = 3274 (m), 2917
˜
(s), 1724 (s), 1634 (s), 1595 (s), 1476 (m), 1231 (s), 1024 (vs.), 820
(s), 757 (s) cm–1. HRMS (ESI): m/z calcd. for C13H8ClNO [M +
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2-Chloroacridin-9(10H)-one (5g): Yellow solid; 217.6 mg, yield
95%. 1H NMR (301 MHz, [D6]DMSO): δ = 11.77 (s, 1 H), 8.17
(dd, J = 8.4, 2.3 Hz, 2 H), 7.82–7.65 (m, 1 H), 7.48 (t, J = 5.8 Hz,
2 H), 7.30–7.14 (m, 2 H) ppm. 13C NMR (76 MHz, [D6]DMSO): δ
= 176.72, 142.10, 141.35, 138.55, 134.34, 128.88, 126.54, 122.10,
121.87, 121.20, 119.63, 117.97, 116.84 ppm. IR: ν = 3264 (m), 2918
˜
(s), 1714 (s), 1633 (s), 1595 (s), 1473 (m), 1279 (s), 1024 (vs.), 818
(s), 761 (s), 674 (m) cm–1. HRMS (ESI): m/z calcd. for C13H8ClNO
[M + H]+ 230.0294; found 230.0289.
Methyl 9-Oxo-9,10-dihydroacridine-3-carboxylate (5h): Yellow so-
lid; 210.1 mg, yield 83%. 1H NMR (301 MHz, [D6]DMSO): δ =
11.91 (s, 1 H), 8.25 (d, J = 8.4 Hz, 1 H), 8.18 (dd, J = 8.1, 1.2 Hz,
1 H), 8.11 (d, J = 1.3 Hz, 1 H), 7.75–7.67 (m, 1 H), 7.64 (dd, J =
8.4, 1.5 Hz, 1 H), 7.48 (d, J = 8.3 Hz, 1 H), 7.29–7.18 (m, 1 H),
3.87 (s, 3 H) ppm. 13C NMR (76 MHz, [D6]DMSO): δ = 177.00,
166.14, 141.56, 140.93, 134.45, 133.87, 127.29, 126.56, 123.22,
122.07, 121.30, 120.68, 119.71, 119.66, 118.05, 53.13 ppm. IR: ν =
˜
3274 (m), 2989 (s), 2942 (s), 2287 (m), 1731 (s), 1630 (vs.), 1527
8
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Job/Unit: O50161
/KAP1
Date: 08-04-15 15:01:04
Pages: 10
Modular Synthesis of Acridine Derivatives
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oration from
a chloroform/cyclohexane solution. CCDC-
Received: February 2, 2015
1042187 contains the supplementary crystallographic data for
Published Online: ᭿
Eur. J. Org. Chem. 0000, 0–0
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9

Job/Unit: O50161
/KAP1
Date: 08-04-15 15:01:04
Pages: 10
X. Pang, Z. Lou, M. Li, L. Wen, C. Chen
FULL PAPER
Modular Cyclization
X. Pang, Z. Lou, M. Li,* L. Wen,
C. Chen* ......................................... 1–10
Tandem Arylation/Friedel–Crafts Reac-
tions of o-Acylanilines with Diaryliodon-
ium Salts: A Modular Synthesis of Acrid-
ine Derivatives
A tandem cyclization reaction to produce
acridine derivatives was realized with o-
acylanilines and diaryliodonium salts un-
der Cu-catalyzed or metal-free reaction
conditions at elevated temperature.
Keywords: Synthetic methods / Domino re-
actions / Homogeneous catalysis / Copper /
Nitrogen heterocycles
10
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