Fatemeh Jalili1, Mahmoud Zarei1, Mohammad Ali Zolfigol1, Ardeshir Khazaei1. 1. Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali-Sina University 6517838965 Hamedan Iran Mahmoud8103@yahoo.com zolfi@basu.ac.ir mzolfigol@yahoo.com Khazaei_1326@yahoo.com.
Nowadays, porous materials such as metal–organic frameworks (MOFs) are of great interest to scientists.[1,2] These crystalline materials comprise metal and organic compounds as the nucleus and ligands, respectively. MOFs are multifunctional materials that have been used as adsorbents for the storage and separation of gas, drug delivery, catalyst, proton conductivity and heavy metal adsorbents.[3-9] Post- modification and synthesis of MOFs with acid functional groups and metal have been reported for the transportation of organic compounds, oxidation, and synthesis of biological compounds.[10] Lillerud et al. reported the first MOFs based on Zr, such as Zr-UiO-66-PDC.[11] Considering this, the new class of porous catalyst with sulfonic and phosphorus acid tag-MOFs have been applied in the preparation of pyrimido[4,5-b]quinolones and dicyanomethylene pyridine derivatives – N-amino-2-pyridone and pyrano [2,3-c]pyrazole derivatives.[12-15]Anion exchange is an architectonic method for the preparation of ionic liquids (ILs) and/or molten salts (MSs) with several opposing ions that cannot be synthesized directly. Our research group has introduced MSs with N–S bonds as a new category of catalyst and reagent based on organic materials.[16-24] Now, we combine the porous materials MOF Zr-UiO-66-PDC with ClSO3H, to prepare [Zr-UiO-66-PDC-SO3H]Cl as a novel porous catalyst for ILs.Recently, N-heterocyclic scaffold compounds have been considered as candidates for the design and discovery of new biologically active compounds. It is very important to supply new and easy methods for the preparation of target compounds with unique features. In this regard, 1,4-dihydropyridine structures containing uracil and henna (2-hydroxynaphthalene-1,4-dione) moieties are suitable candidates for biological and pharmacological purposes.[25-29] These molecules have been used as drugs in furnidipine and alogliptin (Fig. 1).[30,31] Also, scaffolds with uracil moieties have been reported as having antitumour,[32] cardiotonic,[33] hepatoprotactive,[34] antihypertensive,[35] antibronchitic[36] and antifungal activity.[37] Therefore, the appearance of novel and simple organic synthetic approaches for the efficient preparation of this type of heterocycle is an interesting challenge. Since scaffolds with uracil and henna moieties are of biological interest,[38,39] we synthesize 1,4-dihydropyridine with uracil and henna moieties.
Fig. 1
Biological compounds containing uracil, henna and dihydropyridine moieties in their structures.
In continuation of our investigation on the development and preparation of MOFs with sulfonic acid tags and organic molecules with henna moieties,[40] in this paper, we prepare [Zr-UiO-66-PDC-SO3H]FeCl4 as an efficient and novel porous catalyst for new dihydrobenzo[g]pyrimido[4,5-b]quinoline derivatives by condensation reaction of 2-hydroxynaphthalene-1,4-dione, 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione and various aldehydes (mono and bis) under solvent free conditions at 100 °C (Fig. 2).
Fig. 2
Preparation of dihydrobenzo[g]pyrimido[4,5-b]quinoline using [Zr-UiO-66-PDC-SO3H]FeCl4.
Experimental
Preparation of [Zr-UiO-66-PDC-SO3H]FeCl4
Initially, our MOFs [Zr-UiO-66-PDC] were synthesized according to a previously reported methodology.[41] In a round-bottomed flask, 50 mL, a mixture of ClSO3H (2 mmol, 0.134 mL) and [Zr-UiO-66-PDC] (0.564 g) in dry CH2Cl2 (30 mL) at 0 °C was stirred for 2 hours. After this, a white precipitate appeared which was separated (by centrifugation) and dried under vacuum. Then, according to the anion exchange method, a mixture of [Zr-UiO-66-PDC-SO3H]Cl (2 g) and FeCl3 (5 mmol, 0.81 g) was stirred in a mortar at 50 °C for 2 hours. After completion of the reaction, the reaction mixture was cooled down to room temperature. Finally, acetone was used to purify the [Zr-UiO-66-PDC-SO3H]FeCl4via trituration (Fig. 3).
Fig. 3
Preparation of [Zr-UiO-66-PDC-SO3H]FeCl4.
General procedure for the synthesis of dihydrobenzo[g]pyrimido[4,5-b]quinoline derivatives using [Zr-UiO-66-PDC-SO3H]FeCl4
In a 15 mL round-bottomed flask, a mixture of 2-hydroxynaphthalen-1,4-dione (henna, 1 mmol, 0.174 g), 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (1 mmol, 0.155 g) and aldehyde (1 mmol) in the presence of 10 mg of [Zr-UiO-66-PDC-SO3H]FeCl4 was stirred at 100 °C under solvent-free conditions. After the completion of the reactions which were monitored by the TLC technique (2 : 3 n-hexane : ethyl acetate). The described catalyst was separated from the reaction mixture by centrifugation (1000 rpm) after adding 10 mL of EtOH as solvent. Finally, after the evaporation of the solvent at room temperature, pure product was obtained by washing with hot ethanol and water (Fig. 2).
To improve the catalytic application of MOFs, we have designed and synthesized [Zr-UiO-66-PDC-SO3H]Cl. Post-functionalization of [Zr-UiO-66-PDC] occurred by preparing [Zr-UiO-66-PDC-SO3H]FeCl4 using FeCl3 in a mortar at room temperature (Fig. 3). [Zr-UiO-66-PDC-SO3H]FeCl4 has a dual role as a Brønsted-Lewis acid catalyst for the preparation of biological compounds. For more detail, full characterization of [Zr-UiO-66-PDC-SO3H]FeCl4 as a catalyst was conducted by FT-IR, VSM, EDX, FE-SEM, elemental mapping, SEM and TEM techniques.
Synthesis and characterization of [Zr-UiO-66-PDC-SO3H]FeCl4 as a new metal–organic framework (MOF)
The FT-IR analysis of ZrCl4, [Zr-UiO-66-PDC], [Zr-UiO-66-PDC-SO3H]Cl and [Zr-UiO-66-PDC-SO3H]FeCl4 is shown in Fig. 4. The broad peak at 2700–3500 cm−1 is related to the OH of SO3H functional group. The aromatic C–H and CC stretching bands are respectively at 2924 and 1626 cm−1. The absorption bands at 1042 and 1136 cm−1 are related to N–S and O–S bond stretching. Furthermore, the absorption bands at 587 cm−1 are linked to the stretching vibrational modes of Fe–Cl groups in FeCl4. The FT-IR spectrum difference between starting materials and [Zr-UiO-66-PDC-SO3H]FeCl4 verified the structure of the catalyst.
Fig. 4
FT-IR spectra of ZrCl4, [Zr-UiO-66-PDC], [Zr-UiO-66-PDC-SO3H]Cl and [Zr-UiO-66-PDC-SO3H]FeCl4.
The materials in the structure of [Zr-UiO-66-PDC-SO3H]FeCl4 were characterized by energy dispersive X-ray spectroscopy (EDX) (Fig. 5). The [Zr-UiO-66-PDC-SO3H]FeCl4 confirmed the existence of Zr, C, O, S, Cl, N and Fe atoms. Furthermore, [Zr-UiO-66-PDC-SO3H]Cl as a well-dispersed material, was determined and verified by SEM-elemental mapping (Fig. 5).
Fig. 5
Upper: energy dispersive X-ray spectroscopy (EDX) of [Zr-UiO-66-PDC-SO3H]FeCl4. Lower: elemental mapping analysis of [Zr-UiO-66-PDC-SO3H]FeCl4.
Also, SEM images of [Zr-UiO-66-PDC-SO3H]FeCl4 were recorded to investigate the morphology (Fig. 6). The obtained images show the face centred cubic (fcu) structure. In addition, the topography of [Zr-UiO-66-PDC-SO3H]FeCl4 was studied more closely using transmission electron microscopy (TEM) as shown in Fig. 7. We can see that [Zr-UiO-66-PDC-SO3H]FeCl4 is a fcu topological network with 12-connected Zr clusters.
Fig. 6
FE-SEM images of [Zr-UiO-66-PDC-SO3H]FeCl4.
Fig. 7
TEM of [Zr-UiO-66-PDC-SO3H]FeCl4.
After the preparation of [Zr-UiO-66-PDC-SO3H]FeCl4via the anion exchange method, it was tested as a catalyst for the synthesis of new dihydrobenzo[g]pyrimido[4,5-b]quinoline derivatives with uracil and henna (2-hydroxynaphthalene-1,4-dione) moieties. The above-mentioned products were obtained by reaction of 4-methoxy benzaldehyde (1.0 mmol, 0.136 g), 2-hydroxynaphthalen-1,4-dione (1 mmol, 0.174 g), and 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (1 mmol, 0.155 g) as a model for the optimization of the reaction conditions. The optimized data is listed in Table 1. As shown in Table 1, the best choice for the synthesis of 5-(4-methoxyphenyl)-1,3-dimethyl-5,12-dihydrobenzo[g]pyrimido[4,5-b]quinoline-2,4,6,11(1H,3H)-tetraone was achieved in the presence of 10 mg [Zr-UiO-66-PDC-SO3H]FeCl4 under solvent-free conditions (entry 4, Table 1). The model reaction was also studied under different temperatures and several solvents – H2O, EtOH, DMF, n-hexane, EtOAc, CH3CN (5 mL) – in the presence of 10 mg of [Zr-UiO-66-PDC-SO3H]FeCl4. As is shown, the results of the reaction did not improve (Table 1, entries 10–15).
Effect of different amounts of catalyst, solvent and different temperatures, on the synthesis of 5-(4-methoxyphenyl)-1,3-dimethyl-5,12-dihydrobenzo[g]pyrimido[4,5-b]quinoline-2,4,6,11(1H,3H)-tetraone
Entry
Amount of catalyst (mg)
Temp. (o C)
Solvent (10 mL)
Time (min)
Yield (%)
1
—
100
—
50
Trace
2
5
100
—
50
45
3
7
100
—
50
50
4
10
100
—
50
90
5
15
100
—
50
90
6
10
r.t.
—
50
75
7
10
50
—
50
70
8
10
70
—
50
20
9
15
120
—
50
90
10
10
Reflux
H2O
50
85
11
10
Reflux
EtOH
50
70
12
10
100
DMF
50
40
13
10
Reflux
n-Hexane
50
Trace
14
10
Reflux
EtOAc
50
Trace
15
10
Reflux
CH3CN
50
45
After optimizing the reaction conditions, [Zr-UiO-66-PDC-SO3H]FeCl4 (10 mg) is applied to synthesize a range of novel biological and pharmacological candidate compounds using various aromatic aldehydes such as trephetaldehyde, iso-trephetaldehyde, bearing electron-donating and electron-withdrawing groups, 2-hydroxynaphthalen-1,4-dione and 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione. As shown in Table 2, the obtained results indicated that [Zr-UiO-66-PDC-SO3H]FeCl4 is appropriate for the preparation of target molecules in high to excellent yield (70–90%) with relatively short reaction times (70–120 min).
Synthesis of dihydrobenzo[g]pyrimido[4,5-b]quinoline derivatives using [Zr-UiO-66-PDC-SO3H]FeCl4
In the proposed mechanism, the [Zr-UiO-66-PDC-SO3H]FeCl4 catalyst activates the carbonyl functional group of aldehyde. To investigate the activation of the aldehyde, 4-methoxy benzaldehyde was reacted with [Zr-UiO-66-PDC-SO3H]FeCl4 at room temperature. The FT-IR spectra of the subsequent reaction mixtures were examined.[15,42,43] The absorption bond of CO of the 4-methoxy benzaldehyde at 1704 cm−1, was changed to 1704, 1705 or 1711 cm−1 by [Zr-UiO-66-PDC], [Zr-UiO-66-PDC-SO3H]Cl and [Zr-UiO-66-PDC-SO3H]FeCl4 (Fig. 8). Then, the henna (2-hydroxynaphthalen-1,4-dione) moiety reacts with the carbonyl of the aldehyde by removing one H2O molecule, to give intermediate (I) (Fig. 9). In the next step, 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione reacts with intermediate (I) to give intermediate (II). In the next two steps, intermediate (II) gives the desired product after intramolecular cyclization and the loss of another molecule of H2O.
Fig. 8
FT-IR spectra of 4-methoxy benzaldehyde in percent of [Zr-UiO-66-PDC], [Zr-UiO-66-PDC-SO3H]Cl and [Zr-UiO-66-PDC-SO3H]FeCl4.
Fig. 9
Proposed mechanism for the synthesis of dihydrobenzo[g]pyrimido[4,5-b]quinoline derivatives using [Zr-UiO-66-PDC-SO3H]FeCl4.
To evaluate the performance of [Zr-UiO-66-PDC-SO3H]FeCl4 as a catalyst for the synthesis of dihydrobenzo[g]pyrimido[4,5-b]quinoline derivatives, we tested various acid catalysts (organic and inorganic) in the reaction of 4-methoxy benzaldehyde (1.0 mmol, 0.136 g), 2-hydroxynaphthalen-1,4-dione (1 mmol, 0.174 g), 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (1 mmol, 0.155 g) as evaluated in Table 3. The obtained results which are collected in Table 3 show that, [Zr-UiO-66-PDC-SO3H]FeCl4 is the best catalyst for the synthesis of novel dihydrobenzo[g]pyrimido[4,5-b]quinoline derivatives. The obtained results of catalytic activity and reusability of [Zr-UiO-66-PDC-SO3H]FeCl4 are shown in Fig. 10. As mentioned above, [Zr-UiO-66-PDC-SO3H]FeCl4 was separated by centrifugation and reused without significant reduction in its catalytic activity. Recyclability of the catalyst was also studied using the one-pot reaction of 4-methoxy benzaldehyde (1.0 mmol, 0.136 g), 2-hydroxynaphthalen-1,4-dione (1 mmol, 0.174 g), 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (1 mmol, 0.155 g) as a model under the above-mentioned optimized reaction conditions. We found that [Zr-UiO-66-PDC-SO3H]FeCl4 can be reused up to four times without noticeable changes in its catalytic activity.
Evaluation of various catalysts for the synthesis of 5-(4-methoxyphenyl)-1,3-dimethyl-5,12-dihydrobenzo[g]pyrimido[4,5-b]quinoline-2,4,6,11(1H,3H)-tetraone with [Zr-UiO-66-PDC-SO3H]FeCl4
Entry
Catalyst
Amount of catalyst (mol%)
Time (min)
Yield (%)
1
NaOH
10
60
25
2
Et3N
10
65
—
3
K2CO3
10
70
Trace
4
P-TSA
10
90
—
5
SSA [44,45]
10 mg
120
Trace
6
GTBSA [46]
10 mg
80
45
7
[PVI-SO3H]FeCl4 [19]
10 mg
70
70
8
MIL-100(Cr)–NHEtN(CH2PO3H2)2 [15]
10 mg
60
65
9
Fe3O4@Co(BDC-NH2) [47]
10 mg
50
35
10
CQDs-N(CH2PO3H2)2 [48]
10 mg
80
43
11
TTPA[49]
10
100
55
12
MIL-101(Cr)–N(CH2PO3H2)2 [12]
10 mg
60
80
13
FeCl3
10
120
50
14
ZrCl4
10
120
55
15
Zr-UiO-66-PDC
10 mg
120
40
16
[Zr-UiO-66-PDC-SO3H]Cl
10 mg
65
75
17
[Zr-UiO-66-PDC-SO3H]FeCl4
10 mg
50
90
Fig. 10
Recyclability of [Zr-UiO-66-PDC-SO3H]FeCl4 in the synthesis of dihydrobenzo[g]pyrimido[4,5-b]quinoline derivatives.
Conclusion
In this study, we have designed, synthesized and introduced [Zr-UiO-66-PDC-SO3H]FeCl4 as a novel mesoporous catalyst, which was fully characterized using various techniques. To the best of our knowledge, this catalyst is the first MOF that was synthesized via the anion exchange method. [Zr-UiO-66-PDC-SO3H]FeCl4 is an efficient catalyst. It was tested for the preparation of new dihydrobenzo[g]pyrimido[4,5-b]quinoline derivatives with henna and uracil moieties which have biological interest.
Authors: S Waitschat; D Fröhlich; H Reinsch; H Terraschke; K A Lomachenko; C Lamberti; H Kummer; T Helling; M Baumgartner; S Henninger; N Stock Journal: Dalton Trans Date: 2018-01-23 Impact factor: 4.390
Authors: Iman Yousefi; Mehdi Pakravan; Hoda Rahimi; Abbas Bahador; Zahra Farshadzadeh; Ismael Haririan Journal: Mater Sci Eng C Mater Biol Appl Date: 2017-02-20 Impact factor: 7.328
Authors: JeongYong Lee; Omar K Farha; John Roberts; Karl A Scheidt; SonBinh T Nguyen; Joseph T Hupp Journal: Chem Soc Rev Date: 2009-03-17 Impact factor: 54.564
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