Novel Multicomponent Synthesis of PyridineâPyrimidines and Their

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Novel Multi-component Synthesis of Pyridine-pyrimidines and Their Bis-derivatives Catalyzed by Triazine Diphosphonium Hydrogen Sulfate Ionic Liquid Supported on Functionalized Nano-silica Fahime Rahmani, Iraj Mohammadpoor-Baltork, Ahmad Reza Khosropour, Majid Moghadam, Shahram Tangestaninejad, and Valiollah Mirkhani ACS Comb. Sci., Just Accepted Manuscript • DOI: 10.1021/acscombsci.7b00079 • Publication Date (Web): 07 Dec 2017 Downloaded from http://pubs.acs.org on December 8, 2017

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ACS Combinatorial Science

Novel Multi-component Synthesis of Pyridinepyrimidines and Their Bis-derivatives Catalyzed by Triazine Diphosphonium Hydrogen Sulfate Ionic Liquid Supported on Functionalized Nano-silica Fahime Rahmani,† Iraj Mohammadpoor-Baltork,*,† Ahmad Reza Khosropour,*,† Majid Moghadam,† Shahram Tangestaninejad,† and Valiollah Mirkhani† †

Catalysis Division, Department of Chemistry, University of Isfahan, Isfahan 81746-73441, Iran.

ABSTRACT: In this article, we report an efficient synthesis of 1,3-dimethyl-5-aryl-7-(pyridine3(2)(4)-yl)pyrimidine-2,4(1H,3H)-diones via a three-component reaction of aryl aldehydes, 1,3dimethyl-6-aminouracil and carbonitriles in the presences of triazine diphosphonium hydrogen sulfate ionic liquid supported on functionalized nano-silica (APTADPHS-nSiO2) as a reusable catalyst under microwave irradiation and solvent-free conditions. The bis-derivatives of pyridinepyrimidines were also efficiently prepared from dialdehydes and dinitriles. In addition, 3-methyl1H-pyrazole-5-amine was used successfully instead of 1,3-dimetyl-6-aminouracil under the same conditions to afford the corresponding products in high yields. The catalyst can be reused at least five times without any significant loss of its activity. The easy recovery, reusability and excellent activity of the catalyst as well as easy work-up are other noteworthy advantages of this method.

KEYWORDS: one-pot synthesis, pyrimidine derivatives, multi-component reactions, acidic ionic liquid, microwave irradiation

1 Environment ACS Paragon Plus

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INTRODUCTION During the past years, multi-component reactions (MCRs) have attracted great attention in many useful organic transformations because of their widespread applications for the production of biologically active compounds and complex heterocyclic molecules as well as in the total synthesis of natural products. Compared to conventional multistep synthetic approaches, the MCRs provide outstanding benefits such as straightforward experimental procedures, high atom economy, high yields, less formation of by-products, short reaction times, and avoidance of complex isolation and purification of intermediates.1-4 Pyrimidines have emerged as promising and valuable functional components of the very important heterocycles in organic and medicinal chemistry.5-8 Heterocycles containing pyrimidine nucleus possess a variety of useful biological properties including antibacterial, anti-inflammatory, anti HIV, antimalarial, antihypertensive, antihistaminic, antifungal, antioxidant, antiplasmodial, antitumor, anticancer, antiviral and analgesia activities.9-18 Due to their wide range of interesting properties and applications, the development of an efficient and novel methodology for the synthesis of pyridinepyrimidine derivatives is of practical importance and is highly desirable. Recently, several useful organic transformations using supported nano-catalysts have been reported by our research group.19 In continuation of our research in the development of new applications of APTADPHS-nSiO2 catalyst,20 we disclose herein for the first time a novel one-pot multi-component synthesis of pyridine-pyrimidines and their bis-derivatives via APTADPHS-nSiO2 catalyzed reaction between aldehydes/dialdehydes, 1,3-dimethyl-6-aminouracil or 3-methyl-1H-pyrazol-5-amine and carbonitriles/dinitriles under microwave irradiation and solvent-free conditions (Scheme 1).


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Scheme 1. Synthesis of Pyridine-pyrimidines and Their Bis-derivatives Catalyzed by APTADPHS-nSiO2

RESULTS AND DISCUSSION Initially, to find the optimum conditions, the reaction between 4-nitrobenzaldehyde 1{1} (1 mmol), 1,3-dimethyl-6-aminouracil 2{1}(1 mmol) and pyridine-2-carbonitrile 3{1}(1 mmol) was carried out as a model under microwave irradiation solvent-free conditions. In the absence of catalyst, the reaction did not proceed and the starting materials remained intact in the reaction mixture (Table 1, entry 1). The model reaction was then performed in the presence of different catalysts under microwave irradiation (350 W, 90 °C) and solvent-free conditions (entries 2-9). Among the screened catalysts, APTADPHS-nSiO2 was

found to be the most efficient catalyst and gave the desired product 4 {1, 1, 1} in

95% yield (entry 9). The same reaction was also carried out in various solvents at different temperatures in the presence of 3 mol% APTADPHS-nSiO2 (entries 10-13). As can be seen, the reaction



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did not proceed in H2O and CHCl3, and very low yields of the desired product was obtained in EtOH and toluene solvents. Thus solvent-free conditions is essential for this reaction. Next, the effect of the catalyst amount, temperature and MW power on the yield of the product was investigated. The amount of the catalyst ranging from 2 to 4 mol% were evaluated and the highest yield of the desired product was obtained in presence of 3 mol% catalyst (entries 9, 14-16). The effect of temperature was examined in the range of 70-100 °C under microwave irradiation (350 W) and solvent free conditions (entries 9, 17-19). When the temperature was increased from 70 to 90 °C, the yield of product 4 {1, 1, 1} was improved from 58% to 95%. Further increase in temperature to 100 °C had no significant effect on the product yield. Consequently, 90 °C was selected as optimum temperature for all the reactions. Finally, the MW power was optimized by carrying out the model reaction at 250, 300, 350 and 400 W (entries 9, 20-22), under solvent-free conditions at 90 °C. The results indicated that MW irradiation at 350 W gave the highest yield. To clarify the effect of MW, the synthesis of 4 {1, 1, 1} was performed under conventional heating (90 °C) and only 5% of the desired product was produced even after 4 h (entry 23). On the basis of the obtained results, the optimal conditions were 1:1:1:0.03 molar ratio of aldehyde, 1,3-dimethyl-6-amnio uracil, pyridine-2carbonitrile and APTADPHS-nSiO2 using MW power of 350 W at temperature of 90 °C under solventfree conditions. Table 1. Optimization of the Reaction Conditions for the Synthesis of 4 {1, 1, 1}a NO2

CHO

O H 3C +

1 {1}

Entry 1

N

O H3C

N

N

N

+

O NO2

CN

N

NH2

O

CH3

N

N

N

CH3

2 {1}

3 {1}

Catalyst (mol %)

Solvent

None

None

4 {1, 1, 1}

T (°C)

Time (min)

Yieldb (%)

90

30

0


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2

FeCl3 (3)

None

90

15

10

3

ZnCl2 (3)

None

90

15

10

4

AlCl3 (3)

None

90

15

25

5

BiCl3 (3)

None

90

15

35

6

H3PW12O40.H20 (3)

None

90

15

64

7

P-TSA (3)

None

90

15

60

8

[Hmim]HSO4 (3)

None

90

15

65

9

APTADPHS-nSiO2 (3)

None

90

15

95

10

APTADPHS-nSiO2 (3)

H 2O

90

20

0

11

APTADPHS-nSiO2 (3)

CHCl3

60

20

0

12

APTADPHS-nSiO2 (3)

EtOH

75

20

20

13

APTADPHS-nSiO2 (3)

Toluene

90

20

10

14

APTADPHS-nSiO2 (2)

None

90

15

55

15

APTADPHS-nSiO2 (2.5)

None

90

15

77

16

APTADPHS-nSiO2 (4)

None

90

15

95

17

APTADPHS-nSiO2 (3)

None

70

15

60

18

APTADPHS-nSiO2 (3)

None

80

15

72

19

APTADPHS-nSiO2 (3)

None

100

15

95

20c

APTADPHS-nSiO2 (3)

None

90

15

58

21d

APTADPHS-nSiO2 (3)

None

90

15

85

22e

APTADPHS-nSiO2 (3)

None

90

15

95

23f

APTADPHS-nSiO2 (3)

None

90

240

5

a

Reaction was performed with an applied power of 350 W. bIsolated yield. cReaction was performed with an applied power of 250 W. dReaction was performed with an applied power of 300 W. eReaction was performed with an applied power of 400 W. f Reaction was performed under conventional heating conditions.

Under these optimized conditions, the scope of this reaction was investigated using a series of aldehydes, amines and carbonitriles (Figure 1). As illustrated in Table 2, a variety of pyridinepyrimidine derivatives were successfully synthesized in high to excellent yields by the reaction of electron deficient aldehydes, 6-amino-1,3-dimethyluracil and carbonitriles in the presence of APTADPHS-nSiO2 catalyst (Table 2).



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Aryl aldehyde 1:

Amine 2:

Carbonitrile 3:

Figure 1. Diversity of reagents.

Table 2. Synthesis of 1,3-Dimethyl-5-aryl-7-(pyridine-3(2)(4)-yl)pyrimidne-2,4(1H,3H)-diones Catalyzed by APTADPHS-nSiO2a Entry

Product

Time (min)

Yieldb (%)

15

95

1

4 {1, 1, 1}


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2

15

88

15

85

16

90

15

95

15

91

20

72

4 {1, 1, 2}

3

4 {1, 1, 3}

4

4 {2, 1, 1}

5

4 {3, 1, 1}

6

4 {3, 1, 2}

7

[

4 {4, 1, 1}



8

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20

70

20

85

25

95

25

90

4 {5, 1, 1}

9

4 {6, 1, 1}

10

4 {11, 1, 5}

11

4 {3, 1, 5} a

Reaction conditions : Aldehyde (1 mmol), aminouracil (1 mmol), pyridine carbonitrile (1 mmol), APTADPHS-nSiO2 (3 mol%) under microwave irradiation (350 W, 90 oC) and solvent-free conditions. bIsolated yield.

The results showed that the electronic properties of the substituents on the aromatic aldehydes significantly affect the yield of the products and the reaction times. It is noteworthy that, while aldehydes containing electron-withdrawing groups are converted to their corresponding pyridinepyrimidine derivatives by the present protocol under the optimum reaction conditions, those with electron-donating groups (such as 4-methylbenzaldehyde and 4-methoxybenzaldehyde) remain intact. In this respect, the reaction of an equimolar mixture of 4-nitrobenzaldehyde and 4-methylbenzaldehyde with 1,3-dimethy-6-aminouracil and pyridine-2-carbonitril was investigated under MW irradiation and solvent-free conditions. As shown in Scheme 2, 4-nitrobenzaldehyde is selectively transformed to the corresponding pyridine-pyrimidine derivative, whereas, 4-methylbenzaldehyde remains intact in the reaction mixture. 8 Environment ACS Paragon Plus

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NO2

O H3C

N N

O CHO

CHO

N

+ O

NO2

CN

+

+ CH3

N

N

N

CH3

O H3C

N

NH2

CH3

90% N

+

APTADPHS-nSiO2 (3 mol%)

90 oC, MW (350 W) Solvent-f ree

CH3

O H3C O

N

N N

N

N

CH3 0%

Scheme 2. Selective Conversion of 4-Nitrobenzaldehyde into the Corresponding Pyridine-pyrimidine in the Presence of 4-Methylbenzaldehyde Catalyzed by APTADPHS-nSiO2

Next, we investigated the versatility of this method using dialdehydes under the optimized conditions. In this respect, treatment of terephthaldialdehyde or isophthaldialdehyde with 6-amino-1,3dimethyluracil and pyridine carbonitriles provided the desired bis-derivatives in high yields within short reaction times (Table 3). Table 3. Synthesis of Bis-pyridine-pyrimidines from Dialdehydes Catalyzed by APTADPHS-nSiO2a

Entry

Product

Time (min)


Yieldb (%)


1

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20

90

20

88

20

80

20

90

5 {7, 1, 1}

2

5 {7, 1, 2} N

CH3 O

3 H3C

N

N

N

O

N

N O N

N

N

N

CH3 O

CH3

5 {7, 1, 3}

4

5 {8, 1, 1}


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5

20

80

20

80

5 {8, 1, 2}

6

5 {8, 1, 3} a

Reaction conditions: Dialdehyde (1 mmol), aminouracil (2 mmol), pyridine carbonitrile (2 mmol), catalyst (6 mol%) under microwave irradiation (350 W, 90 oC) and solvent-free conditions. bIsolated yield.

In an alternative route, benzene-1,4-dicarbonitrile was used instead of pyridine carbonitriles. Unlike the previous reactions, in this case, solvent-free condition was not appropriate (Table S1, Supporting Information). For this purpose, the reaction was carried out in different solvents and acetic acid was found to be the most suitable solvent for this reaction. It is also noteworthy that even in acetic acid solvent, the yield of the product was higher in the presence of catalyst, indicating the efficiency of the catalyst. Under these conditions, 4-nitro- and 3-nitrobenzaldehyde reacted efficiently with benzene-1,4dicarbonitrile and 1,3-dimethy-6-aminouracil in the presence of APTADPHS-nSiO2 and the desired bis-products were obtained in 80% and 75% yields, respectively (Scheme 3).



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Scheme 3. Synthesis of Bis-pyrimidines from Benzene-1,4-dicarbonitril Catalyzed by APTADPHS-nSiO2

To further investigate the substrate scope, 1,3-dimethyl-6-aminouracil 2 {1} was replaced with 3methyl-1H-pyrazole-5-amine 2 {2}. As depicted in Table 4, 3-methyl-1H-pyrazole-5-amine 2 {2} was treated with various aldehydes and pyridine carbonitriles in the presence of APTADPHS-nSiO2

catalyst under the same conditions to afford the desired products in 75-95% yields. It is worth mentioning that, to the best of our knowledge, the synthesis of pyridine-pyrimidines and their bisderivatives via such a one-pot multi-component reaction is reported here for the first time.

Table 4. Synthesis of 4-Aryl-3-methyl-6-(pyridin-2(3)(4)-yl)-1H-pyrazolo[3,4-d]pyrimidines Catalyzed by APTADPHS-nSiO2

Entry

Product

Time (min)


Yielda (%)

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1

10

95

15

90

15

85

15

80

7 {3, 2, 1}

2

7 {2 ,2, 1}

3

7 {2, 2, 2}

4

7 {3, 2, 2}

5

15

90

7 {3, 2, 3}

15

6

7 {5, 2, 1}


75


7

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15

76

15

85

7 {9, 2, 1}

8

7 {10, 2, 1} a

Isolated yield.

The structures of all products were elucidated by FT-IR, 1H NMR and

13

C NMR spectra and by

elemental analysis. As a representative example, the 1H NMR (400 MHz) spectrum of the product 4 {3, 1, 2} displayed signals at δ 9.52 (d, J = 2.2 Hz, 1H), 8.96 (d, J = 2.2 Hz, 1H), 8.77-8.81 (m, 2H), 8.408.43 (m, 2H), 8.07 (d, J = 8.0 Hz, 1H) and 7.29 (d, J = 5.0 Hz, 1H) for eight aromatic protons of pyridine rings. In addition, the signals due to methyl groups were observed at δ 3.69 (s, 3H) and 3.68 (s. 3H). In the FT-IR spectrum of the product, the characteristic absorption bands at around 3115 cm-1 (CH-aromatic), 2988 cm-1 (CH-aliphatic), 1694 cm-1 (C=O), 1640 cm-1 (C=N) and 1468 cm-1 (C=C), 1081 and 1012 cm-1 (C-N), 772 and 734 (CH-bending) were observed. The

13

C NMR (100 MHz)

spectrum exhibited signals at δ 158.9 and 150.5 for the carbonyl carbons and at δ 167.0, 162.0, 155.1, 149.5, 146.4, 137.0, 131.8, 130.3, 123.7 and 105.4 for the aromatic carbons. Furthermore, the methyl carbons showed their signals at δ 30.8 and 28.3. A plausible mechanism for the APTADPHS-nSiO2 catalyzed synthesis of 1, 3-dimethyl-5-aryl-7(pyridine-3(2)(4)-yl)pyrimidine-2,4(1H,3H)-diones is suggested in Scheme 4. Initially, the aldehyde 1 is actived by the catalyst to give A. Aminouracil 2 then attacks A to furnish B, which undergoes a


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hetero Diels-Alder reaction with carbonitrile 3 in the presence of the catalyst to produce intermediate C. Ultimately, oxidative aromatization of C under air and in the presence of the catalyst, affords the desired product and releases the catalyst for the next run.

a

t-H Ca r i

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Scheme 4. Plausible Mechanism for the Synthesis of Pyridine-pyrimidines Catalyzed by APTADPHS-nSiO2

Catalyst Recovery and Reuse The reusability and recycling of catalyst is one of the valuable advantages of green and efficient catalysts. Hence, the reusability of the catalyst was investigated in the reaction of 4-nitrobenzaldehyde (3 mmol) with 1,3-dimethyl-6-aminouracil (3 mmol) and pyridine-2-carbonitrile (3 mmol) in the presence of APTADPHS-nSiO2 (0.09 mmol, 135 mg) under MW irradiation (350 W, 90 °C) and solvent-free conditions. After completion of the reaction, EtOH was added, the catalyst was separated by centrifugation and washed several times with EtOH. It was then dried, weighted and reused in the



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next run without any reactivation or regeneration. As shown in Table 5, the catalyst could be reused for five consecutive times without significant loss of its activity or lowering the yield of the product. The recovery rate of the catalyst was about 97-98% for each run. Table 5. Reusability of the APTADPHS-nSiO2 Catalyst in the Synthesis of 4 {1, 1, 1}a Run

a

Yielda (%)

1

95

Recovery rate of the catalyst mg (%) 135 (-)

2

93

132 (98)

3

91

129 (98)

4

89

127 (98)

5

86

123 (97)

6

85

121 (98)

Reaction conditions: 4-nitrobenzaldehyde (3 mmol), 6-amino-1,3-dimethyluracil (3 mmol), pyridine-2-carbonitrile (3 mmol) and catalyst (0.09 mmol, 135 mg) under microwave irradiation (350 W, 90 oC) and solvent-free conditions. bIsolated yield.

CONCLUSION In summary, we have disclosed a novel, simple, efficient and new route for the synthesis of a variety of pyridine-pyrimidine derivatives via a one-pot multicomponent reaction of aldehydes, 1,3-dimethyl-6aminouracil or 3-methyl-1H-pyrazole-5-amine and carbonitriles using APTADPHS-nSiO2 as a reusable catalyst under microwave irradiation and solvent-free conditions. In addition, the attractive synthesis of bis-derivatives of pyridine-pyrimidines from dialdehydes and dinitrile in the presence of this catalytic system has been developed. Friendly experimental conditions, short reaction times, high yield of the products, easy recovery and reuse of the catalyst and prevention of toxic solvent, make this method valuable for the synthesis of pyridine-pyrimidine derivatives.

EXPERIMENTAL SECTION General Information. Melting points were determined using a Stuart Scientific SMP2 apparatus. FT-IR spectra were recorded on a Nicolet-Impact 400D instrument in the range of 400-4000 cm-1. The 1

H and

13

C NMR (400 and 100 MHz) spectra were recorded in a DMSO-d6 solution on a Bruker16 Environment ACS Paragon Plus

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Avance 400 spectrometer. Elemental analysis was done on LECO, CHNS-932 analyzer. The microwave system used in these experiments includes the following items: Micro-SYNTH Labstation, equipped with a glass door, a dual magnetron system with a pyramid-shaped diffuser, 1000 W delivered power, exhaust system, magnetic stirrer, ‘‘quality pressure” sensor for flammable organic solvents, and a ATCFO fiber optic system for automatic temperature control. Typical Procedure for the Synthesis of 1,3-Dimethyl-5-(4-nitrophenyl)-7-(pyridin-2yl)pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione 4a {1, 1, 1} in the Presence of APTADPHS-nSiO2 Catalyst. A mixture of 4-nitrobenzaldehyde (1.0 mmol), 1,3-dimethyl-6-aminouracile (1.0 mmol), pyridine-2-carbonitrile (1.0 mmol) and APTADPHS-nSiO2 (3 mol%, 45 mg) was subjected to microwave irradiation (350 W, 90 °C) under solvent-free conditions. The progress of the reaction was monitored by TLC (eluent: petroleum ether/EtOAc, 2:5). After completion of the reaction, the mixture was stirred with 10 mL EtOH in a few minutes and the catalyst was filtered. The reaction mixture was cooled to room temperature, the precipitated product was filtered and washed with EtOH (2 × 5 mL) to afford the pure product 4 {1, 1, 1} in 95% yield. Mp: 290-292 oC. IR (KBr): νmax = 3123 (CHaromatic), 2976 (CH-aliphatic), 1678 (C=O), 1665 (C=N), 1556 (N=O), 1503 (C=C), 1450 (C=C), 1352 (N=O), 1012 (C-N), 830 (CH-bending), 734 (CH-bending) cm-1. 1H NMR (400 MHz, DMSO-d6): δ = 8.73 (d, J = 8.4 Hz, 1H, ArH), 8.42 (d, J = 8.4 Hz, 1H, ArH), 8.35 (d, J = 8.0 Hz, 1H, ArH), 8.20 (d, J = 8.8 Hz, 2H, ArH), 7.88 (d, J = 8.4 Hz, 1H, ArH), 7.56 (d, J = 8.4 Hz, 1H, ArH), 7.48 (d, J = 8.4 Hz, 1H, ArH), 3.75 (s, 3H, CH3), 3.28 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6): δ = 170.0 (ArC), 166.8 (C=N), 162.0 (C=N), 159.1 (C=O), 150.7 (C=N), 150.0 (C=O), 147.8 (Ar-CH), 145.0 (Ar-C), 131.8 (Ar-C), 129.9 (Ar-CH), 124.2 (Ar-CH), 123.7 (Ar-CH), 122.6 (Ar-CH), 120.5 (Ar-CH), 109.3 (Ar-C), 30.8 (CH3), 28.1 (CH3). Anal. Calcd for C19H14N6O4: C, 58.46; H, 3.61; N, 21.53. Found: C, 58.40; H, 3.59; N, 21.49.



Page 18 of 22

ASSOCIATED CONTENT Supporting Information. Experimental procedure, 1H and 13C NMR spectra and elemental analysis data for all products. This material is available free of charge via the Internet at http://pubs.acs.org. AUTHOR INFORMATION Corresponding Author *Phone: 98 313 7934927. Fax: 98 313 6689732. E-mails: [email protected], [email protected] Notes The authors declare no competing financial interest.

ACKNOWLEDGMENTS The authors are grateful to the Research Council of the University of Isfahan for financial support of this work. REFERENCES (1) Haji, M. Multicomponent Reactions: A Simple and Efficient Route to Heterocyclic Phosphonates. Beilstein J. Org. Chem. 2016, 12, 1269-1301. (2) Biggs-Houck, J. E.; Younai, A.; Shaw. J. T. Recent Advances in Multicomponent Reactions for Diversity-oriented Synthesis. Curr. Opin. Chem. Biol. 2010, 14, 371-382. (3) Váradi, A.; Palmer, T. C.; Dardashti, R. N.; Majumdar, S. Isocyanide-based Multicomponent Reactions for the Synthesis of Heterocycles. Molecules 2016, 21, 1-22. (4) Carlone, A.; Cabrera, S.; Marigo, M.; Jørgensen, K. A. A New Approach for an Organocatalytic Multicomponent Domino Asymmetric Reaction. Angew. Chem. Int. Ed. 2007, 46, 1101-1104.


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Isfahani, A.; Mohammadpoor-Baltork, I.; Tangestaninejad, S.; Moghadam, M.; Mirkhani, V.; Amiri Rudbari, H. Diastereoselective Synthesis of Symmetrical and Unsymmetrical Tetrahydropyridines Catalyzed by Bi(III) Immobilized on Triazine Dendrimer Stabilized Magnetic Nanoparticles. ACS Comb. Sci. 2017, 19, 356-364. (20) Rahmani, F.; Mohammadpoor-Baltork, I.; Khosropour, A. R.; Moghadam, M.; Tangestaninejad, S.; Mirkhani, V. Efficient One-pot synthesis of New Fused Pyridines and Bis-pyridines Catalyzed by Triazine Diphosphonium Hydrogen Sulfate Ionic Liquid Supported on Functionalized Nanosilica. Tetrahedron Lett. 2016, 57, 2294-2297.



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For Table of Contents Use Only Novel Multi-component Synthesis of Pyridine-pyrimidines and Their Bis-derivatives Catalyzed by Triazine Diphosphonium Hydrogen Sulfate Ionic Liquid Supported on Functionalized Nano-silica

Fahime Rahmani,† Iraj Mohammadpoor-Baltork,*,† Ahmad Reza Khosropour,*,† Majid Moghadam,† Shahram Tangestaninejad,† and Valiollah Mirkhani†

A new and efficient method for the synthesis of a variety of pyridine-pyrimidines and their bisderivatives using APTADPHS-nSiO2 as a reusable catalyst under microwave irradiation is reported.

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Novel Multicomponent Synthesis of PyridineâPyrimidines and Their

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