# Poly(4-Vinylpyridinium)Hydrogen Sulfate Catalyzed an Efficient and Ecofriendly Protocol for the One-Pot Multicomponent Synthesis of 1,8-Acridinediones in Aqueous Medium

Authors: Janardhan Banothu; Rajitha Bavantula; Peter A. Crooks
Journal: Journal of Chemistry
 (2013)

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## Abstract

Highly efficient, ecofriendly, and improved protocol for the synthesis of 1,8-acridinediones has been developedvia one-pot multicomponent condensation of 1,3-cyclohexanedione/dimedone, aromatic aldehydes, and ammonium acetate utilizing poly(4-vinylpyridinium)hydrogen sulfate as catalyst in aqueous medium. Excellent yields in shorter reaction time, simple work-up procedure, easy recovery, and reusability of the catalyst are attractive features of this green protocol.


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## Body

## 1. Introduction

Multicomponent reactions (MCRs) have emerged as an efficient and powerful tool in modern organic chemistry towards the generation of highly diverse and complex product from readily available substrates in a single operation without isolation of intermediates in minimal time with maximum selectivity, high atom economy, and high purity with excellent yields [1]. In addition, reactions under aqueous medium have received considerable attention in organic synthesis, because of both economic and environmental safety reasons [2]. Moreover, heterogeneous catalysts have advantages over homogeneous catalysts in terms of efficiency, operational simplicity, recovery from the reaction mixture, and reusability [3].1,8-Acridinediones having 1,4-dihydropyridine (1,4-DHP) parent nucleus, which are versatile intermediates in the synthesis of numerous pharmaceuticals including those for the treatment of cardiovascular diseases and hypertension as effective calcium channel blockers [4, 5], Alzheimer’s disease, and as chemosensitizer in tumor therapy [6, 7], are also used as laser dyes [8, 9] and photo initiators for radical polymerization reactions [10–12].In view of the above applications, many methods have been developed including microwave irradiation [13, 14], using various catalytic systems such as p-toluenesulfonic acid [15], ceric ammonium nitrate [16], InCl3 [17], CeCl3·7H2O [18], L-proline, Zn(OAc)2·7H2O [19], In(OTf)3 [20], MCM-41-SO3H [21], Amberlite IR-120H [22], methanesulfonic acid [23], silica bonded s-sulfonic acid [24], silica-supported preyssler nanoparticles [25], p-dodecylbenzenesulfonic acid [26], carbon based solid acid [27], and ionic liquids [28, 29]. However, most of these methods suffer from drawbacks such as low yield of the product, longer reaction time, multistep process, formation of side products, critical isolation procedure, use of hazardous organic solvents and expensive catalysts, difficult in recovery and reusability of the catalyst. Thus, there is a need for the development of new and efficient methods for the preparation of such compounds in high yields and under mild reaction conditions.In continuation of our studies towards the development of novel methodologies for the synthesis of biologically active heterocyclic compounds [30, 31], herein we report an ecofriendly method for the synthesis of 1,8-acridinediones using poly(4-vinylpyridinium)hydrogen sulfate [P(4-VPH)HSO4] as an efficient, heterogeneous, and recyclable catalyst in aqueous medium.


## 2. Results and Discussions

The schematic representation for the synthesis of title compounds (5a–k and 6a–k) via one-pot multicomponent condensation of 1,3-cyclohexanedione (1)/dimedone (2) aromatic aldehydes (3a–k), and ammonium acetate (4) utilizing P(4-VPH)HSO4 as catalyst in aqueous medium was shown in Scheme 1. The catalyst P(4-VPH)HSO4 was prepared according to the literature procedure [32].Scheme 1
P(4-VPH)HSO4 catalyzed synthesis of 1,8-acridinediones.In order to find out the optimal conditions, a model reaction was carried out by the condensation of dimedone (2) with p-chlorobenzaldehyde (3b) and ammonium acetate (4) in aqueous medium at different temperatures by varying the amount of catalyst, and the results were summarized in Table 1. From Table 1, we found that only 0.02 g of P(4-VPH)HSO4 at 80°C is sufficient for completion of the reaction with maximum yield (Table 1, Entry 7). We also observed that as the amount of catalyst increases >0.02 g and the temperature >80°C, the yield of the product has decreased due to the unidentified impurities.Table 1
Optimizing the reaction conditionsa.
Entry
P(4-VPH)HSO4(g)
Temperature (°C)
Time (min)
Yieldb (%)
1
—
RT
120
—
2
—
80
120
28
3
—
Reflux
120
36
4
0.01
RT
60
Trace
5
0.01
80
30
74
6
0.01
Reflux
30
74
7
0.02
80
10
95
8
0.02
Reflux
10
95
9
0.03
80
10
94
10
0.03
Reflux
10
92
aDimedone (2 mmol), p-chlorobenzaldehyde (1 mmol), ammonium acetate (3 mmol), and P(4-VPH)HSO4 in aqueous medium.
bIsolated yields.At these optimal conditions (0.02 g of P(4-VPH)HSO4, 80°C, aqueous medium), we have synthesized various 1,8-acridinediones (5a–k and 6a–k) using different aromatic aldehydes with excellent yields in shorter reaction times (Table 2). All the synthesized compounds were characterized by their spectral studies and compared with the literature values where both were in good agreements. After completion of the reaction, the catalyst was recovered, washed with dichloromethane, dried, and reused for subsequent reactions for additional five times, and a slight decrease in its activity in terms of product yield was observed (Table 2, Entry 13).Table 2
P(4-VPH)HSO4catalyzed one-pot synthesis of 1,8-acridinediones (5a–k and 6a–k).
Entrya
Aldehyde
Product
Time (min)
Yieldb(%)
Melting point (°C)
Found
Lit. [Ref.]
1
Benzaldehyde
5a
15
92
278–280
279–281 [16]
2
4-Chlorobenzaldehyde
5b
10
94
297–299
298-299 [16]
3
3-Nitrobenzaldehyde
5c
15
89
278–281
282–284 [16]
4
4-Methoxybenzaldehyde
5d
10
91
306–308
304–306 [16]
5
3,4-Dimethoxybenzaldehyde
5e
10
93
355-356
—
6
4-Hydroxybenzaldehyde
5f
15
90
305–307
307–309 [16]
7
3-Methoxy-4-hydroxybenzaldehyde
5g
15
90
281–283
—
8
3-Ethoxy-4-hydroxybenzaldehyde
5h
20
88
299–302
—
9
5-Bromo-2-hydroxybenzaldehyde
5i
20
91
272–274
—
10
3,5-Dibromo-2-hydroxybenzaldehyde
5j
20
90
250-251
—
11
5-Chloro-2-hydroxybenzaldehyde
5k
20
92
295–297
—
12
Benzaldehyde
6a
10
93
258–260
258–260 [18]
13
4-Chlorobenzaldehyde
6b
10
95 (93, 90,  89, 86, 84)c
299–301
298–300 [18]
14
3-Nitrobenzaldehyde
6c
15
88
290–293
294–296 [18]
15
4-Methoxybenzaldehyde
6d
10
90
273-274
272-273 [23]
16
3,4-Dimethoxybenzaldehyde
6e
10
94
259–261
258–260 [13]
17
4-Hydroxybenzaldehyde
6f
15
92
361–363
>300 [23]
18
3-Methoxy-4-hydroxybenzaldehyde
6g
15
92
294–296
294-295 [18]
19
3-Ethoxy-4-hydroxybenzaldehyde
6h
15
89
280–282
—
20
5-Bromo-2-hydroxybenzaldehyde
6i
20
90
254-255
—
21
3,5-Dibromo-2-hydroxybenzaldehyde
6j
20
90
294-295
—
22
5-Chloro-2-hydroxybenzaldehyde
6k
20
92
234–236
—
aReaction conditions: 1,3-cyclohexanedione/dimedone (2 mmol), arylaldehyde (1 mmol), ammonium acetate (3 mmol),  and P(4-VPH)HSO4(0.02 g), heat at 80°C for 10–20 min in 5 mL of H2O.
bIsolated yields.
cYields refer to the reusability of the catalyst over additional five times.The catalytic efficiency of P(4-VPH)HSO4 was compared with some other reported catalysts for the synthesis of 3,4,6,7-tetrahydro-3,3,6,6-tetramethyl-9-phenylacridine-1,8-(2H,5H,9H,10H)-dione (6b). The results proved that the P(4-VPH)HSO4 is an efficient catalyst in terms of product yield and reaction times (Table 3).Table 3
Comparing the catalytic efficiency of P(4-VPH)HSO4for the synthesis of 6b with some reported catalysts.
Entrya
Catalyst (g)
Reaction conditions
Time (min)
Yield (%)Ref.
1
L-Proline (0.041 g)
H2O, Reflux
120
88 [19]
2
Zn(OAc)·2H2O (0.0172 g)
H2O, Reflux
120
91 [19]
3
CAN (0.0274 g)
PEG 400, Rt
25
92 [16]
4
InCl3(0.0022 g)
EtOH, Rt
27
93 [17]
5
CeCl3·7H2O  (0.0182 g)
Ionic liquid, 100°C
180
89 [18]
6
MSAa (0.0096 g)
Solvent-free, 120°C
60
92 [23]
7
CBSAb (0.0056 g)
Solvent-free, 100°C
15
90 [27]
8
P(4-VPH)HSO4 (0.02 g)
H2O, 80°C
10
95 [present work]
aMSA: methanesulfonic acid; bCBSA: carbon-based solid acid
For comparison, mole percentages were converted into grams.A plausible mechanism for the formation of 1,8-acridinediones catalysed by P(4-VPH)HSO4 is shown in Scheme 2. In the presence of catalyst, the electrophilicity of aldehydic carbonyl carbon increases and readily reacts with the enolic form of 1,3-dicarbonyl compounds which resulted the formation of chalcone derivative [C]. Compound [C] reacts with aminated 1,3-dicarbonyl compound [B] which is formed in situ by the reaction of 1,3-dicarbonyl compound with ammonium acetate that furnished the corresponding 1,8-acridinediones through the cyclisation followed by the dehydration.Scheme 2
Proposed mechanism for the formation of 1,8-acridinediones.


## 3. Experimental

All the chemicals were procured from Aldrich/Merck, and solvents were used without further purification. Melting points were recorded on Stuart SMP30 apparatus and are uncorrected. Thin layer chromatography was performed with F254 silica-gel precoated sheets using hexane/ethyl acetate (8 : 2) as eluent, visualized by UV light and iodine vapor. Products were characterized by comparing with the authentic samples and by spectral data (IR,1H NMR, and Mass). IR spectra were recorded on Perkin-Elmer 100S spectrophotometer using KBr disk. 1H NMR spectra were recorded on Bruker 400 MHz spectrometer using DMSO-d6 as solvent and TMS as internal standard. Elemental analysis was performed on a Carlo Erba model EA1108. Mass spectra were recorded on a Jeol JMSD-300 spectrometer.


### 3.1. General Procedure for the Synthesis of 1,8-Acridinediones

To a mixture of 1,3-cyclohexanedione/dimedone (2 mmol), arylaldehyde (1 mmol), and ammonium acetate (3 mmol) in 5 mL of water, 0.02 g of poly(4-vinylpyridinium)hydrogen sulfate was added and stirred at 80°C for an appropriate time as shown in Table2. After completion of the reaction (TLC monitoring), the solid separated out was filtered, washed with water, dried, and recrytallized from ethanol/acetic acid to afford the pure 1,8-acridinediones in excellent yields. Aqueous layer containing catalyst was recovered under reduced pressure, dried, and reused for additional five times for subsequent reactions.


### 3.2. Spectral Data of New Compounds

#### 3.2.1. 9-(3,4-Dimethoxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5e)

Pale yellow solid; IR (KBr)υmax (cm−1): 3417 (NH), 1635 (C=O), 1597 (C=C), 1026 (C–O–C); 1H NMR (400 MHz, DMSO-d6): δ 1.75–1.79 (m, 2H), 1.83–1.90 (m, 2H), 2.16–2.19 (m, 4H), 2.45–2.48 (m, 4H), 3.47 (s, 3H), 3.49 (s, 3H), 4.83 (s, 1H), 6.47–6.49 (m, 1H), 6.62 (d, J=8.0 Hz, 1H), 6.74 (s, 1H), 9.42 (s, 1H); MS (ESI) m/z: 354 (M + H)+; anal. calcd. for C21H23NO4: C, 71.37; H, 6.56; N, 3.96; found: C, 71.09; H, 6.71; N, 3.76.


#### 3.2.2. 9-(4-Hydroxy-3-methoxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5g)

Pale yellow solid; IR (KBr)υmax (cm−1): 3411 (NH), 3302 (OH), 1637 (C=O), 1596 (C=C), 1132 (C–O–C); 1H NMR (400 MHz, DMSO-d6): δ 1.76–1.80 (m, 2H), 1.86–1.91 (m, 2H), 2.17–2.20 (m, 4H), 2.45–2.49 (m, 4H), 3.47 (s, 3H), 4.80 (s, 1H), 6.46–6.47 (m, 1H), 6.55 (d, J=8.0 Hz, 1H), 6.73 (s, 1H), 8.49 (s, 1H), 9.41 (s, 1H); MS (ESI) m/z: 340 (M + H)+; anal. calcd. for C20H21NO4: C, 70.78; H, 6.24; N, 4.13; found: C, 70.54; H, 6.43; N, 4.22.


#### 3.2.3. 9-(3-Ethoxy-4-hydroxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5h)

Red solid; IR (KBr)υmax (cm−1): 3414 (NH), 3329 (OH), 1644 (C=O), 1591 (C=C), 1119 (C–O–C); 1H NMR (400 MHz, DMSO-d6): δ 1.29 (t, J=7.2 Hz, 3H), 1.77–1.81 (m, 2H), 1.88–1.93 (m, 2H), 2.19–2.22 (m, 4H), 2.47–2.49 (m, 4H), 3.88–3.93 (m, 2H), 4.81 (s, 1H), 6.45–6.47 (m, 1H), 6.55 (d, J=8.0 Hz, 1H), 6.71 (s, 1H), 8.48 (s, 1H), 9.36 (s, 1H); MS (ESI) m/z: 354 (M + H)+; anal. calcd. for C21H23NO4: C, 71.37; H, 6.56; N, 3.96; found: C, 71.18; H, 6.69; N, 3.80.


#### 3.2.4. 9-(5-Bromo-2-hydroxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5i)

Pale yellow solid; IR (KBr)υmax (cm−1): 3414 (NH), 3279 (OH), 1625 (C=O), 1593 (C=C), 615 (C–Br); 1H NMR (400 MHz, DMSO-d6): δ 1.78–1.83 (m, 2H), 1.92–1.96 (m, 2H), 2.26–2.30 (m, 4H), 2.55–2.61 (m, 4H), 4.84 (s, 1H), 6.65 (d, J=8.4 Hz, 1H), 6.87 (d, J=8.4 Hz, 1H), 7.09–7.12 (m, 1H), 9.82 (s, 1H), 9.91 (s, 1H); MS (ESI) m/z: 411 (M + Na)+; anal. calcd. for C19H18BrNO3: C, 58.78; H, 4.67; N, 3.61; found: C, 58.62; H, 4.83; N, 3.79.


#### 3.2.5. 9-(3,5-Dibromo-2-hydroxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5j)

Yellow solid; IR (KBr)υmax(cm−1): 3415 (NH), 3285 (OH), 1620 (C=O), 1580 (C=C), 616 (C–Br); 1H NMR (400 MHz, DMSO-d6): δ 1.83–1.91 (m, 2H), 1.93–1.97 (m, 2H), 2.30–2.33 (m, 4H), 2.57–2.64 (m, 4H), 4.85 (s, 1H), 6.83 (s, 1H), 7.49 (s, 1H), 9.91 (s, 1H), 10.72 (s, 1H); MS (ESI) m/z: 468 (M + H)+; anal. calcd. for C19H17Br2NO3: C, 48.85; H, 3.67; N, 3.00; found: C, 48.64; H, 3.86; N, 3.12.


#### 3.2.6. 9-(5-Chloro-2-hydroxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5k)

Pale yellow solid; IR (KBr)υmax (cm−1): 3414 (NH), 3280 (OH), 1622 (C=O), 1593 (C=C), 617 (C–Cl); 1H NMR (400 MHz, DMSO-d6): δ 1.79–1.82 (m, 2H), 1.92–1.96 (m, 2H), 2.26–2.29 (m, 4H), 2.54–2.60 (m, 4H), 4.84 (s, 1H), 6.70 (d, J=8.4 Hz, 1H), 6.74 (d, J=8.4 Hz, 1H), 6.97–7.00 (m, 1H), 9.84 (s, 1H), 9.89 (s, 1H); MS (ESI) m/z: 344 (M + H)+; anal. calcd. for C19H18ClNO3: C, 66.38; H, 5.28; N, 4.07; found: C, 66.17; H, 5.40; N, 4.26.


#### 3.2.7. 9-(3-Ethoxy-4-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (6h)

Pale yellow solid; IR (KBr)υmax (cm−1): 3416 (NH), 3277 (OH), 1620 (C=O), 1598 (C=C), 1122 (C–O–C); 1H NMR (400 MHz, DMSO-d6): δ 0.88 (s, 6H), 1.01 (s, 6H), 1.28 (t, J=7.2 Hz, 3H), 1.99 (d, J=16.0 Hz, 2H), 2.17 (d, J=16.0 Hz, 2H), 2.30 (d, J=16.8 Hz, 2H), 2.43 (d, J=16.8 Hz, 2H), 3.85–3.91 (m, 2H), 4.70 (s, 1H), 6.49–6.56 (m, 2H), 6.68 (s, 1H), 8.48 (s, 1H), 9.20 (s, 1H); MS (ESI) m/z: 432 (M + Na)+; anal. calcd. for C25H31NO4: C, 73.32; H, 7.63; N, 3.42; found: C, 73.18; H, 7.77; N, 3.56.


#### 3.2.8. 9-(5-Bromo-2-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (6i)

White solid; IR (KBr)υmax (cm−1): 3415 (NH), 3279 (OH), 1622 (C=O), 1570 (C=C), 656 (C–Br); 1H NMR (400 MHz, DMSO-d6): δ 0.89 (s, 6H), 0.96 (s, 3H), 1.04 (s, 3H), 2.03 (d, J=16.0 Hz, 2H), 2.22–2.57 (m, 6H), 5.03 (s, 1H), 6.95 (d, J=8.8 Hz, 1H), 7.03 (s, 1H), 7.26–7.29 (m, 1H), 9.86 (s, 1H), 10.60 (s, 1H); MS (ESI) m/z: 445 (M + H)+; anal. calcd. for C23H26BrNO3: C, 62.17; H, 5.90; N, 3.15; found: C, 62.04; H, 5.99; N, 3.31.


#### 3.2.9. 9-(3,5-Dibromo-2-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (6j)

Pale yellow solid; IR (KBr)υmax (cm−1): 3416 (NH), 3284 (OH), 1635 (C=O), 1613 (C=C), 665 (C–Br); 1H NMR (400 MHz, DMSO-d6): δ 0.93 (s, 6H), 1.04 (s, 6H), 2.13 (d, J=16.4 Hz, 2H), 2.30 (d, J=16.4 Hz, 2H), 2.46 (d, J=17.6 Hz, 4H), 4.82 (s, 1H), 6.88 (s, 1H), 7.49 (s, 1H), 9.87 (s, 1H), 10.63 (s, 1H); MS (ESI) m/z: 524 (M + H)+; anal. calcd. for C23H25Br2NO3: C, 52.79; H, 4.82; N, 2.68; found: C, 52.65; H, 4.97; N, 2.80.


#### 3.2.10. 9-(5-Chloro-2-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (6k)

White solid; IR (KBr)υmax (cm−1): 3415 (NH), 3285 (OH), 1629 (C=O), 1579 (C=C), 656 (C–Cl); 1H NMR (400 MHz, DMSO-d6): δ 0.89 (s, 6H), 0.97 (s, 3H), 1.04 (s, 3H), 2.03 (d, J=16.0 Hz, 2H), 2.24 (d, J=16.0 Hz, 2H), 2.33 (d, J=17.2 Hz, 2H), 2.54 (d, J=17.2 Hz, 2H), 5.03 (s, 1H), 6.90 (s, 1H), 7.00 (d, J=8.8 Hz, 1H), 7.14–7.17 (m, 1H), 9.82 (s, 1H), 10.58 (s, 1H); MS (ESI) m/z: 400 (M + H)+; anal. calcd. for C23H26ClNO3: C, 69.08; H, 6.55; N, 3.50; found: C, 68.92; H, 6.73; N, 3.68.


## 3.1. General Procedure for the Synthesis of 1,8-Acridinediones

To a mixture of 1,3-cyclohexanedione/dimedone (2 mmol), arylaldehyde (1 mmol), and ammonium acetate (3 mmol) in 5 mL of water, 0.02 g of poly(4-vinylpyridinium)hydrogen sulfate was added and stirred at 80°C for an appropriate time as shown in Table2. After completion of the reaction (TLC monitoring), the solid separated out was filtered, washed with water, dried, and recrytallized from ethanol/acetic acid to afford the pure 1,8-acridinediones in excellent yields. Aqueous layer containing catalyst was recovered under reduced pressure, dried, and reused for additional five times for subsequent reactions.


## 3.2. Spectral Data of New Compounds

### 3.2.1. 9-(3,4-Dimethoxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5e)

Pale yellow solid; IR (KBr)υmax (cm−1): 3417 (NH), 1635 (C=O), 1597 (C=C), 1026 (C–O–C); 1H NMR (400 MHz, DMSO-d6): δ 1.75–1.79 (m, 2H), 1.83–1.90 (m, 2H), 2.16–2.19 (m, 4H), 2.45–2.48 (m, 4H), 3.47 (s, 3H), 3.49 (s, 3H), 4.83 (s, 1H), 6.47–6.49 (m, 1H), 6.62 (d, J=8.0 Hz, 1H), 6.74 (s, 1H), 9.42 (s, 1H); MS (ESI) m/z: 354 (M + H)+; anal. calcd. for C21H23NO4: C, 71.37; H, 6.56; N, 3.96; found: C, 71.09; H, 6.71; N, 3.76.


### 3.2.2. 9-(4-Hydroxy-3-methoxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5g)

Pale yellow solid; IR (KBr)υmax (cm−1): 3411 (NH), 3302 (OH), 1637 (C=O), 1596 (C=C), 1132 (C–O–C); 1H NMR (400 MHz, DMSO-d6): δ 1.76–1.80 (m, 2H), 1.86–1.91 (m, 2H), 2.17–2.20 (m, 4H), 2.45–2.49 (m, 4H), 3.47 (s, 3H), 4.80 (s, 1H), 6.46–6.47 (m, 1H), 6.55 (d, J=8.0 Hz, 1H), 6.73 (s, 1H), 8.49 (s, 1H), 9.41 (s, 1H); MS (ESI) m/z: 340 (M + H)+; anal. calcd. for C20H21NO4: C, 70.78; H, 6.24; N, 4.13; found: C, 70.54; H, 6.43; N, 4.22.


### 3.2.3. 9-(3-Ethoxy-4-hydroxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5h)

Red solid; IR (KBr)υmax (cm−1): 3414 (NH), 3329 (OH), 1644 (C=O), 1591 (C=C), 1119 (C–O–C); 1H NMR (400 MHz, DMSO-d6): δ 1.29 (t, J=7.2 Hz, 3H), 1.77–1.81 (m, 2H), 1.88–1.93 (m, 2H), 2.19–2.22 (m, 4H), 2.47–2.49 (m, 4H), 3.88–3.93 (m, 2H), 4.81 (s, 1H), 6.45–6.47 (m, 1H), 6.55 (d, J=8.0 Hz, 1H), 6.71 (s, 1H), 8.48 (s, 1H), 9.36 (s, 1H); MS (ESI) m/z: 354 (M + H)+; anal. calcd. for C21H23NO4: C, 71.37; H, 6.56; N, 3.96; found: C, 71.18; H, 6.69; N, 3.80.


### 3.2.4. 9-(5-Bromo-2-hydroxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5i)

Pale yellow solid; IR (KBr)υmax (cm−1): 3414 (NH), 3279 (OH), 1625 (C=O), 1593 (C=C), 615 (C–Br); 1H NMR (400 MHz, DMSO-d6): δ 1.78–1.83 (m, 2H), 1.92–1.96 (m, 2H), 2.26–2.30 (m, 4H), 2.55–2.61 (m, 4H), 4.84 (s, 1H), 6.65 (d, J=8.4 Hz, 1H), 6.87 (d, J=8.4 Hz, 1H), 7.09–7.12 (m, 1H), 9.82 (s, 1H), 9.91 (s, 1H); MS (ESI) m/z: 411 (M + Na)+; anal. calcd. for C19H18BrNO3: C, 58.78; H, 4.67; N, 3.61; found: C, 58.62; H, 4.83; N, 3.79.


### 3.2.5. 9-(3,5-Dibromo-2-hydroxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5j)

Yellow solid; IR (KBr)υmax(cm−1): 3415 (NH), 3285 (OH), 1620 (C=O), 1580 (C=C), 616 (C–Br); 1H NMR (400 MHz, DMSO-d6): δ 1.83–1.91 (m, 2H), 1.93–1.97 (m, 2H), 2.30–2.33 (m, 4H), 2.57–2.64 (m, 4H), 4.85 (s, 1H), 6.83 (s, 1H), 7.49 (s, 1H), 9.91 (s, 1H), 10.72 (s, 1H); MS (ESI) m/z: 468 (M + H)+; anal. calcd. for C19H17Br2NO3: C, 48.85; H, 3.67; N, 3.00; found: C, 48.64; H, 3.86; N, 3.12.


### 3.2.6. 9-(5-Chloro-2-hydroxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5k)

Pale yellow solid; IR (KBr)υmax (cm−1): 3414 (NH), 3280 (OH), 1622 (C=O), 1593 (C=C), 617 (C–Cl); 1H NMR (400 MHz, DMSO-d6): δ 1.79–1.82 (m, 2H), 1.92–1.96 (m, 2H), 2.26–2.29 (m, 4H), 2.54–2.60 (m, 4H), 4.84 (s, 1H), 6.70 (d, J=8.4 Hz, 1H), 6.74 (d, J=8.4 Hz, 1H), 6.97–7.00 (m, 1H), 9.84 (s, 1H), 9.89 (s, 1H); MS (ESI) m/z: 344 (M + H)+; anal. calcd. for C19H18ClNO3: C, 66.38; H, 5.28; N, 4.07; found: C, 66.17; H, 5.40; N, 4.26.


### 3.2.7. 9-(3-Ethoxy-4-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (6h)

Pale yellow solid; IR (KBr)υmax (cm−1): 3416 (NH), 3277 (OH), 1620 (C=O), 1598 (C=C), 1122 (C–O–C); 1H NMR (400 MHz, DMSO-d6): δ 0.88 (s, 6H), 1.01 (s, 6H), 1.28 (t, J=7.2 Hz, 3H), 1.99 (d, J=16.0 Hz, 2H), 2.17 (d, J=16.0 Hz, 2H), 2.30 (d, J=16.8 Hz, 2H), 2.43 (d, J=16.8 Hz, 2H), 3.85–3.91 (m, 2H), 4.70 (s, 1H), 6.49–6.56 (m, 2H), 6.68 (s, 1H), 8.48 (s, 1H), 9.20 (s, 1H); MS (ESI) m/z: 432 (M + Na)+; anal. calcd. for C25H31NO4: C, 73.32; H, 7.63; N, 3.42; found: C, 73.18; H, 7.77; N, 3.56.


### 3.2.8. 9-(5-Bromo-2-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (6i)

White solid; IR (KBr)υmax (cm−1): 3415 (NH), 3279 (OH), 1622 (C=O), 1570 (C=C), 656 (C–Br); 1H NMR (400 MHz, DMSO-d6): δ 0.89 (s, 6H), 0.96 (s, 3H), 1.04 (s, 3H), 2.03 (d, J=16.0 Hz, 2H), 2.22–2.57 (m, 6H), 5.03 (s, 1H), 6.95 (d, J=8.8 Hz, 1H), 7.03 (s, 1H), 7.26–7.29 (m, 1H), 9.86 (s, 1H), 10.60 (s, 1H); MS (ESI) m/z: 445 (M + H)+; anal. calcd. for C23H26BrNO3: C, 62.17; H, 5.90; N, 3.15; found: C, 62.04; H, 5.99; N, 3.31.


### 3.2.9. 9-(3,5-Dibromo-2-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (6j)

Pale yellow solid; IR (KBr)υmax (cm−1): 3416 (NH), 3284 (OH), 1635 (C=O), 1613 (C=C), 665 (C–Br); 1H NMR (400 MHz, DMSO-d6): δ 0.93 (s, 6H), 1.04 (s, 6H), 2.13 (d, J=16.4 Hz, 2H), 2.30 (d, J=16.4 Hz, 2H), 2.46 (d, J=17.6 Hz, 4H), 4.82 (s, 1H), 6.88 (s, 1H), 7.49 (s, 1H), 9.87 (s, 1H), 10.63 (s, 1H); MS (ESI) m/z: 524 (M + H)+; anal. calcd. for C23H25Br2NO3: C, 52.79; H, 4.82; N, 2.68; found: C, 52.65; H, 4.97; N, 2.80.


### 3.2.10. 9-(5-Chloro-2-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (6k)

White solid; IR (KBr)υmax (cm−1): 3415 (NH), 3285 (OH), 1629 (C=O), 1579 (C=C), 656 (C–Cl); 1H NMR (400 MHz, DMSO-d6): δ 0.89 (s, 6H), 0.97 (s, 3H), 1.04 (s, 3H), 2.03 (d, J=16.0 Hz, 2H), 2.24 (d, J=16.0 Hz, 2H), 2.33 (d, J=17.2 Hz, 2H), 2.54 (d, J=17.2 Hz, 2H), 5.03 (s, 1H), 6.90 (s, 1H), 7.00 (d, J=8.8 Hz, 1H), 7.14–7.17 (m, 1H), 9.82 (s, 1H), 10.58 (s, 1H); MS (ESI) m/z: 400 (M + H)+; anal. calcd. for C23H26ClNO3: C, 69.08; H, 6.55; N, 3.50; found: C, 68.92; H, 6.73; N, 3.68.


## 3.2.1. 9-(3,4-Dimethoxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5e)

Pale yellow solid; IR (KBr)υmax (cm−1): 3417 (NH), 1635 (C=O), 1597 (C=C), 1026 (C–O–C); 1H NMR (400 MHz, DMSO-d6): δ 1.75–1.79 (m, 2H), 1.83–1.90 (m, 2H), 2.16–2.19 (m, 4H), 2.45–2.48 (m, 4H), 3.47 (s, 3H), 3.49 (s, 3H), 4.83 (s, 1H), 6.47–6.49 (m, 1H), 6.62 (d, J=8.0 Hz, 1H), 6.74 (s, 1H), 9.42 (s, 1H); MS (ESI) m/z: 354 (M + H)+; anal. calcd. for C21H23NO4: C, 71.37; H, 6.56; N, 3.96; found: C, 71.09; H, 6.71; N, 3.76.


## 3.2.2. 9-(4-Hydroxy-3-methoxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5g)

Pale yellow solid; IR (KBr)υmax (cm−1): 3411 (NH), 3302 (OH), 1637 (C=O), 1596 (C=C), 1132 (C–O–C); 1H NMR (400 MHz, DMSO-d6): δ 1.76–1.80 (m, 2H), 1.86–1.91 (m, 2H), 2.17–2.20 (m, 4H), 2.45–2.49 (m, 4H), 3.47 (s, 3H), 4.80 (s, 1H), 6.46–6.47 (m, 1H), 6.55 (d, J=8.0 Hz, 1H), 6.73 (s, 1H), 8.49 (s, 1H), 9.41 (s, 1H); MS (ESI) m/z: 340 (M + H)+; anal. calcd. for C20H21NO4: C, 70.78; H, 6.24; N, 4.13; found: C, 70.54; H, 6.43; N, 4.22.


## 3.2.3. 9-(3-Ethoxy-4-hydroxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5h)

Red solid; IR (KBr)υmax (cm−1): 3414 (NH), 3329 (OH), 1644 (C=O), 1591 (C=C), 1119 (C–O–C); 1H NMR (400 MHz, DMSO-d6): δ 1.29 (t, J=7.2 Hz, 3H), 1.77–1.81 (m, 2H), 1.88–1.93 (m, 2H), 2.19–2.22 (m, 4H), 2.47–2.49 (m, 4H), 3.88–3.93 (m, 2H), 4.81 (s, 1H), 6.45–6.47 (m, 1H), 6.55 (d, J=8.0 Hz, 1H), 6.71 (s, 1H), 8.48 (s, 1H), 9.36 (s, 1H); MS (ESI) m/z: 354 (M + H)+; anal. calcd. for C21H23NO4: C, 71.37; H, 6.56; N, 3.96; found: C, 71.18; H, 6.69; N, 3.80.


## 3.2.4. 9-(5-Bromo-2-hydroxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5i)

Pale yellow solid; IR (KBr)υmax (cm−1): 3414 (NH), 3279 (OH), 1625 (C=O), 1593 (C=C), 615 (C–Br); 1H NMR (400 MHz, DMSO-d6): δ 1.78–1.83 (m, 2H), 1.92–1.96 (m, 2H), 2.26–2.30 (m, 4H), 2.55–2.61 (m, 4H), 4.84 (s, 1H), 6.65 (d, J=8.4 Hz, 1H), 6.87 (d, J=8.4 Hz, 1H), 7.09–7.12 (m, 1H), 9.82 (s, 1H), 9.91 (s, 1H); MS (ESI) m/z: 411 (M + Na)+; anal. calcd. for C19H18BrNO3: C, 58.78; H, 4.67; N, 3.61; found: C, 58.62; H, 4.83; N, 3.79.


## 3.2.5. 9-(3,5-Dibromo-2-hydroxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5j)

Yellow solid; IR (KBr)υmax(cm−1): 3415 (NH), 3285 (OH), 1620 (C=O), 1580 (C=C), 616 (C–Br); 1H NMR (400 MHz, DMSO-d6): δ 1.83–1.91 (m, 2H), 1.93–1.97 (m, 2H), 2.30–2.33 (m, 4H), 2.57–2.64 (m, 4H), 4.85 (s, 1H), 6.83 (s, 1H), 7.49 (s, 1H), 9.91 (s, 1H), 10.72 (s, 1H); MS (ESI) m/z: 468 (M + H)+; anal. calcd. for C19H17Br2NO3: C, 48.85; H, 3.67; N, 3.00; found: C, 48.64; H, 3.86; N, 3.12.


## 3.2.6. 9-(5-Chloro-2-hydroxyphenyl)-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (5k)

Pale yellow solid; IR (KBr)υmax (cm−1): 3414 (NH), 3280 (OH), 1622 (C=O), 1593 (C=C), 617 (C–Cl); 1H NMR (400 MHz, DMSO-d6): δ 1.79–1.82 (m, 2H), 1.92–1.96 (m, 2H), 2.26–2.29 (m, 4H), 2.54–2.60 (m, 4H), 4.84 (s, 1H), 6.70 (d, J=8.4 Hz, 1H), 6.74 (d, J=8.4 Hz, 1H), 6.97–7.00 (m, 1H), 9.84 (s, 1H), 9.89 (s, 1H); MS (ESI) m/z: 344 (M + H)+; anal. calcd. for C19H18ClNO3: C, 66.38; H, 5.28; N, 4.07; found: C, 66.17; H, 5.40; N, 4.26.


## 3.2.7. 9-(3-Ethoxy-4-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (6h)

Pale yellow solid; IR (KBr)υmax (cm−1): 3416 (NH), 3277 (OH), 1620 (C=O), 1598 (C=C), 1122 (C–O–C); 1H NMR (400 MHz, DMSO-d6): δ 0.88 (s, 6H), 1.01 (s, 6H), 1.28 (t, J=7.2 Hz, 3H), 1.99 (d, J=16.0 Hz, 2H), 2.17 (d, J=16.0 Hz, 2H), 2.30 (d, J=16.8 Hz, 2H), 2.43 (d, J=16.8 Hz, 2H), 3.85–3.91 (m, 2H), 4.70 (s, 1H), 6.49–6.56 (m, 2H), 6.68 (s, 1H), 8.48 (s, 1H), 9.20 (s, 1H); MS (ESI) m/z: 432 (M + Na)+; anal. calcd. for C25H31NO4: C, 73.32; H, 7.63; N, 3.42; found: C, 73.18; H, 7.77; N, 3.56.


## 3.2.8. 9-(5-Bromo-2-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (6i)

White solid; IR (KBr)υmax (cm−1): 3415 (NH), 3279 (OH), 1622 (C=O), 1570 (C=C), 656 (C–Br); 1H NMR (400 MHz, DMSO-d6): δ 0.89 (s, 6H), 0.96 (s, 3H), 1.04 (s, 3H), 2.03 (d, J=16.0 Hz, 2H), 2.22–2.57 (m, 6H), 5.03 (s, 1H), 6.95 (d, J=8.8 Hz, 1H), 7.03 (s, 1H), 7.26–7.29 (m, 1H), 9.86 (s, 1H), 10.60 (s, 1H); MS (ESI) m/z: 445 (M + H)+; anal. calcd. for C23H26BrNO3: C, 62.17; H, 5.90; N, 3.15; found: C, 62.04; H, 5.99; N, 3.31.


## 3.2.9. 9-(3,5-Dibromo-2-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (6j)

Pale yellow solid; IR (KBr)υmax (cm−1): 3416 (NH), 3284 (OH), 1635 (C=O), 1613 (C=C), 665 (C–Br); 1H NMR (400 MHz, DMSO-d6): δ 0.93 (s, 6H), 1.04 (s, 6H), 2.13 (d, J=16.4 Hz, 2H), 2.30 (d, J=16.4 Hz, 2H), 2.46 (d, J=17.6 Hz, 4H), 4.82 (s, 1H), 6.88 (s, 1H), 7.49 (s, 1H), 9.87 (s, 1H), 10.63 (s, 1H); MS (ESI) m/z: 524 (M + H)+; anal. calcd. for C23H25Br2NO3: C, 52.79; H, 4.82; N, 2.68; found: C, 52.65; H, 4.97; N, 2.80.


## 3.2.10. 9-(5-Chloro-2-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-2H,5H-acridine-1,8-dione (6k)

White solid; IR (KBr)υmax (cm−1): 3415 (NH), 3285 (OH), 1629 (C=O), 1579 (C=C), 656 (C–Cl); 1H NMR (400 MHz, DMSO-d6): δ 0.89 (s, 6H), 0.97 (s, 3H), 1.04 (s, 3H), 2.03 (d, J=16.0 Hz, 2H), 2.24 (d, J=16.0 Hz, 2H), 2.33 (d, J=17.2 Hz, 2H), 2.54 (d, J=17.2 Hz, 2H), 5.03 (s, 1H), 6.90 (s, 1H), 7.00 (d, J=8.8 Hz, 1H), 7.14–7.17 (m, 1H), 9.82 (s, 1H), 10.58 (s, 1H); MS (ESI) m/z: 400 (M + H)+; anal. calcd. for C23H26ClNO3: C, 69.08; H, 6.55; N, 3.50; found: C, 68.92; H, 6.73; N, 3.68.


## 4. Conclusion

In conclusion, we have developed a simple, mild, and efficient protocol for the synthesis of 1,8-acridinediones utilizing poly(4-vinylpyridinium)hydrogen sulphate as catalyst in aqueous medium. Excellent yields in shorter reaction times, easy work-up procedure, environmentally begin nature, recovery, and reusability of the catalyst are the obvious advantages of this methodology.



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*Source: 850254-2013-08-13.xml*