Personal Use Only Not For Distribution

0 downloads 0 Views 2MB Size Report
Letters in Organic Chemistry. ImpactFactor:0.664. ISSN: 1570-1786. eISSN: 1875-6255. BENTHAM. SCIENCE. Shahin Khalilian. 1. , Shahrzad ...

361 Letters in Organic Chemistry, 2017, 14, 361-367

RESEARCH ARTICLE ISSN: 1570-1786 eISSN: 1875-6255

An Eco-Friendly and Highly Efficient Synthesis of Pyrimidinones Using a TiO2-CNTs Nanocomposite Catalyst

Impact Factor: 0.664

BENTHAM SCIENCE

Shahin Khalilian1, Shahrzad Abdolmohammadi1,2,* and Fereshteh Nematolahi1,2 Department of Chemistry, 2Young Researchers and Elite Club, East Tehran Branch, Islamic Azad University, P.O. Box 18735-138, Tehran, Iran

nl y

1

O

Abstract: Background: The recent development of using heterogeneous catalysts in organic synthesis has increased the need for fine metal oxide nanoparticles. Nanosized titanium dioxide nanoparticles (TiO2 NPs) can be used in several organic and inorganic transformations because of their superior properties such as high catalytic activity, non-toxicity, easily availability, moisture stability and reusability. Pyrimidinones are privileged heterocycles in the field of drugs and pharmaceutical industry.

on al

DOI: 10.2174/1570178614666170321113926

Results: A series of 2-amino-6-aryl-5,6-dihydro-4(3H)-pyrimidinones were synthesized in high yields (90-98%) via a simple one-pot three-component coupling reaction using the synthesized TiO 2-CNTs nanocomposite with the weight ratio of 50:50 as an efficient and recyclable catalyst. All synthesized compounds were well characterized by their satisfactory elemental analyses, IR, 1H and 13C NMR spectroscopy. The synthesized catalyst was fully characterized by XRD, SEM, and elemental analysis.

tri

Received: November 18, 2016 Revised: March 08, 2017 Accepted: March 08, 2017

U

ARTICLE HISTORY

bu tio n

se

Method: The current methodology deals with the direct assembly of Meldrum’s acid, aromatic aldehydes, and guanidine nitrate in the presence of a catalytic amount of the synthesized TiO2-CNTs nanocomposite could be utilized to afford 2-amino-6-aryl-5,6-dihydro-4(3H)-pyrimidinones under solventfree conditions within 2-3 h.

rD

is

Conclusion: We have developed a general and highly efficient TiO2-CNTs nanocomposite catalyzed procedure for the synthesis of 2-amino-6-aryl-5,6-dihydro-4(3H)-pyrimidinones from a one-pot threecomponent coupling reaction of Meldrum’s acid, aromatic aldehydes, and guanidine nitrate with high yields under solvent-free conditions. This new protocol has revealed several advantages such as recyclability of catalyst, short reaction times, high to excellent yields of products and solvent-free conditions.

Pe rs

1. INTRODUCTION

Fo

Keywords: 2-Amino-6-aryl-5,6-dihydro-4(3H)-pyrimidinone, aromatic aldehydes, eco-friendly protocol, guanidine nitrate, Meldrum’s acid, recyclability of catalyst, solvent-free, TiO2-CNTs nanocomposite.

ot

The recent development of using heterogeneous catalysts in organic synthesis has increased the need for fine metal oxide nanoparticles [1-4]. Nanosized titanium dioxide nanoparticles (TiO2 NPs) can be used in several organic and inorganic transformations because of their superior properties such as high catalytic activity, non-toxicity, easy availability, moisture stability and reusability [5-14]. In order to improve the morphology, structural, chemical, electrical, and optical properties of nanoparticles, carbon nanotubes (CNTs) are used as a support [15, 16]. Recently, the use of TiO2 NPs loaded on the carbon nanotubes (TiO2-CNTs) as a heterogeneous catalyst has attracted the attention owing to its

N

Letters in Organic Chemistry

Send Orders for Reprints to [email protected]

*Address correspondence to this author at the Department of Chemistry, East Tehran Branch, Islamic Azad University, P.O. Box 18735-138, Tehran, Iran; Tel: +98-21-3359 4950; Fax: +98-21-3358 4011; E-mails: [email protected]; [email protected] 1875-6255/17 $58.00+.00

exceptional physical properties, such as large specific surface area, and excellent physiochemical characteristic [17, 18]. Pyrimidinones are privileged heterocycles in the field of drugs and pharmaceutical industry [19]. Some significant biological activities, such as antiviral, antibacterial, antihypertensive, antitumor and calcium blockers effects have been observed for these compounds [20]. Pyrimidinone derivatives have also emerged as core units in some natural marine products, such as batzelladine and carambine alkaloids, which have been used potentially as HIV-gp-120CD4 inhibitors [21]. The synthesis of 2-aminopyrimidinones attracts widespread interest due to their biological potential [22-24]. In this paper, we envisioned that the direct assembly of Meldrum’s acid 1, aromatic aldehydes 2, and guanidine nitrate 3 in the presence of a catalytic amount of TiO2-CNTs nanocomposite could be utilized to afford 2-amino-6-aryl-

© 2017 Bentham Science Publishers

362 Letters in Organic Chemistry, 2017, Vol. 14, No. 5

Khalilian et al. Ar

O

+ O

O

Ar

1

6

NH

O

O

H

. HNO3 NH2

+ H2N

80 0C, Solvent-free

1

4

O

3

N H

2

NH2

4a-k

3

2a-k

N

5

Nano TiO2-CNTs

1a, 4a Ar = C6H5, 1b, 4b Ar = 4-Br-C6H4, 1c, 4c Ar = 3-Cl-C6H4, 1d, 4d Ar = 2,4-Cl2-C6H3, 1e, 4e Ar = 4-NC-C6H4, 1f, 4f Ar = 4-CH3O-C6H4, 1g, 4g Ar = 4-CH3-C6H4, 1h, 4h Ar = 3-O2N-C6H4, 1i, 4i Ar = Furan-2-yl, 1j, 4j Ar = Indol-3-yl, 1k, 4k Ar = Thiophen-2-yl

Scheme (1). Synthesis of 2-amino-6-aryl-5,6-dihydro-4(3H)-pyrimidinone derivatives using a TiO2-CNTs nanocomposite.

To optimize the reaction conditions, we carried out the experiments using 4-bromobenzaldehyde 2b as a model substrate for the reaction with Meldrum’s acid 1 and guanidine nitrate 3 (Table 1).

O

2. RESULTS AND DISCUSSION

analysis technique and the results show that the weight ratio was 50:50.

nl y

5,6-dihydro-4(3H)-pyrimidinones 4 in a very simple and solvent-free route (Scheme 1).

tri

In order to find the optimized reaction temperature, the model reaction was also carried out at different temperature. It was shown that, the temperature increasing more than 80oC, did not affect the yield of corresponding product (Table 1, entries 3 and 5).

is

U

To confirm the influence of the reaction media on the yield and composition of the reaction product, the model reaction was performed using different solvents. We found

rD

Fo

N

ot

Pe rs

on al

For this purpose, first we prepared the TiO2-CNTs nanocomposite via a sonochemical method adopting the approach of Salavati, et al. [30]. The XRD pattern of the synthesized TiO2-CNTs nanocomposite shown in Fig. (1) indicates that only anatase particles form of TiO2 can be observed in the composite. The morphology of the TiO2-CNTs composite which is a continuous and mesoporous anatase TiO2 layer over the CNTs, was also revealed by SEM image (Fig. 2). The chemical composition of the catalyst was determined by the elemental

Fig. (1). XRD pattern of the synthesized TiO2-CNTs nanocomposite.

bu tio n

To determine the effectiveness of the TiO2-CNTs nanocomposite as catalyst, the model reaction was carried out in the absence of catalyst. After 6 h, only 41% of product was obtained (Table 1, entry 1). Further, we have investigated the same reaction using different amounts of the TiO2-CNTs nanocomposite catalyst (10, 15, and 20 mol%). It was found that 15 mol% of catalyst was enough to push the reaction forward (Table 1, entries 2-4).

se

In our ongoing efforts in developing nanostructured catalysts for the efficient synthetic methods for the construction of potential bioactive heterocyclic compounds [25-29], we have found that the TiO2-CNTs nanocomposite is suitable for the preparation of 2-amino-6-aryl-5,6-dihydro-4(3H)pyrimidinone derivatives 4 by the three-component coupling reaction of Meldrum’s acid, aromatic aldehydes, and guanidine nitrate at 80oC under solvent-free conditions.

An Eco-Friendly and Highly Efficient Synthesis of Pyrimidinones

Table 1.

Nanocatalyst (mol% with Respect to TiO2)

Solvent

Temp. (˚C)

Time (h)

Yield (%)a

1

No catalyst

none

80

6

41

2

TiO2-CNTs (10%)

none

80

2.5

58

3

TiO2-CNTs (15%)

none

80

2.5

96

4

TiO2-CNTs (20%)

none

80

2.5

97

5

TiO2-CNTs (15%)

none

100

2.5

96

6

TiO2-CNTs (15%)

H2O

reflux

3

90

7

TiO2-CNTs (15%)

EtOH

reflux

3

79

8

TiO2-CNTs (15%)

CH2Cl2

reflux

4

73

9

TiO2-CNTs (15%)

DMF

reflux

2

84

O

Isolated yield.

Yield(%)a,b

Time (h)

U

Ar

3

M.p. (˚C)

Obsd.

Lit.

263-264

267-268 [23]

4a

C6H5

4b

4-Br-C6H4

2.5

4c

3-Cl-C6H4

2.5

93

4d

2,4-Cl2-C6H 3

3

90

290-291

294 [23]

4e

4-NC-C6H4

2

96

294-296

297 [23]

4f

4-CH3O-C6H 4

3

94

277-278

278-279 [23]

96

270-272

274-275 [23]

93

255-257

258 [23]

96

268-270

----

95

252-253

----

98

276-277

----

4h

3-O2N-C6H 4

2

4i

Furan-2-yl

2.5

4j

Indol-3-yl

3

4k

Thiophen-2-yl

is

2

Fo

4-CH3-C6H 4

3 1

286-288

289-290 [23]

264-266

260-262 [23]

tri

96

rD

Pe rs 4g

92

bu tio n

se

Synthesis of 2-amino-6-aryl-5,6-dihydro-4(3H)-pyrimidinones 4a-k using a TiO2-CNTs catalyst under solvent-free conditions.

Product

a

nl y

Entry

Table 2.

363

Optimization the reaction conditions in the synthesis of 4b.

on al

a

Letters in Organic Chemistry, 2017, Vol. 14, No. 5

13

Yields refer to those of pure isolated products characterized by IR, H and C NMR spectral data and by elemental analyses. In all cases, the reaction mixture was stirring at 80 ˚C, for 2-3 h under solvent-free conditions.

N

ot

b

Fig. (2). SEM image of the synthesized TiO2-CNTs nanocomposite.

that the best results were obtained under solvent-free conditions (Table 1, entries 3 and 6-9). To explore the scope and limitation of this new procedure, we have extensively utilized various substituted aromatic aldehydes for the reaction with Meldrum’s acid and guanidine nitrate to obtain desired products under the optimized conditions (Table 2). The isolated compounds (4a-k) were characterized by IR, 1H NMR and 13C NMR spectroscopic data and also by elemental analyses. A suggested mechanism for this reaction is provided in Scheme 2. In this pathway, it is feasible that TiO2 NPs participate in two following reaction steps. The initial step is the formation of alkene 7, which occurs from a Knoevenagel condensation between Meldrum’s acid 1 and aromatic aldehyde 2, via intermediate 5 and 6. The subsequent Michaeltype addition of guanidine nitrate 3 to alkene 7 generates the

364 Letters in Organic Chemistry, 2017, Vol. 14, No. 5

Khalilian et al. O O Ar O

O

TiO2 NPs

H

O

CNTs

O

Ti

5

O

O

H O

O

CNTs

Ar

O O

O O

H OH

O + O

O

Ar

H

OH

O

1

Ar

O O

NH H2N

O

6

2

H O

NH2

O

nl y

H2O

3

Ti

O

O

CNTs

Ar

O

O

O

H N H

NH

se

O

NH2

Ti

O

U

CNTs

NH

O

O

O

H N H

Ti

O

NH

tri

O

on al

is

CNTs

rD

9

Acetone

TiO2 NPs

Tautomerization

Fo

CNTs

ot

Pe rs

Ar

O

8

bu tio n

H

O

7

O

O

O

Ar

HO

HO

N O

N H

Ar

NH2

CO2

N O

10

N H

NH2

4

N

Scheme (2). Suggested mechanism for the reaction of Meldrum’s acid, aromatic aldehydes and guanidine nitrate catalyzed by TiO2-CNTs nanocomposite.

Michael adduct 9, which upon intramolecular cyclization, tautomerization and elimination of acetone gives product 4 after the decarboxylation of intermediate 10. The possibility of recycling of the catalyst was also examined. The catalyst was successfully, recovered by centrifugation as mentioned in general procedure and reused in four subsequent runs in the model reaction for the synthesis of 4b. The activities of the catalyst get affected slightly in terms of yields after three successive runs (Fig. 3). The structures of the compounds were confirmed by their satisfactory elemental analyses, IR, 1H and 13C NMR spectros-

copy. Spectroscopic data are given in the Experimental Section. The synthesized catalyst was fully characterized by XRD, SEM, and elemental analysis. 3. EXPERIMENTAL SECTION 3.1. Materials and Method All chemicals used in this work were purchased from Merck and Fluka in high purity. Melting points were determined with Electrothermal 9100 apparatus. IR spectra were obtained using a Bruker, Equinox 55, Golden Gate Micro-ATR

An Eco-Friendly and Highly Efficient Synthesis of Pyrimidinones

Letters in Organic Chemistry, 2017, Vol. 14, No. 5

several hours. The pure product was obtained by cooling the ethanol solution to room temperature, diluted with H2O (1 mL) and allowed to crystallize. 3.4. Spectroscopic Data 2-Amino-6-phenyl-5,6-dihydro-4(3H)-pyrimidinone (4a) Yield: 0.174g (92%); White solid, M.P. 263-264oC (lit. 267268oC [23]); IR (KBr): 3330, 3125, 3050, 1639, 1589, 1554, 1498 cm-1; 1H-NMR (300 MHz, DMSO-d6): 2.30 (1H, dd, 2J 15.4, 3J 8.3 Hz, C5H), 2.52 (1H, dd, 2J 15.4, 3J 6.0 Hz, C5H'), 4.65 (1H, t, 3J 6.9 Hz, C6H), 6.69 (2H, br s, NH2), 7.34 (5H, m, ArH), 7.72 (1H, br s, NH) ppm; 13C-NMR (75 MHz, DMSO-d6): 40.1, 53.5, 127.7, 129.2, 130.2, 143.4, 163.6, 177.9 ppm; Anal. Calcd (%) for C10H11N3O (189.22): C, 63.48; H, 5.86; N, 22.21. Found: C, 63.59; H, 5.77; N, 22.39.

nl y

spectrometer. 1H NMR and 13C NMR spectra were recorded on a Bruker DRX-300 AVANCE spectrometer at 300 and 75 MHz respectively using TMS as internal standard and [D6]DMSO as a solvent. Elemental analyses were carried out using a Foss-Heraeus CHN-O-Rapid analyzer. The microscopic morphology of the catalyst was visualized by a scanning electron microcope (SEM) on a Philips, XL-30 scanning electron microscope. Powder X-ray diffraction data were determined on a Rigaku D-max C III, X-ray diffractometer using Cu Kα radiation (λ = 1.54 Å). The composition analysis of the catalyst was obtained from a Carlo ERBA Model EA 1108 analyzer.

365

2-Amino-6-(3-chlorophenyl)-5,6-dihydro-4(3H)-pyrimidinone (4c) Yield: 0.208g (93%); White solid, M.P. 264266oC (lit. 260-262oC [23]); IR (KBr): 3335, 3115, 3050, 1635, 1572, 1547, 1494 cm-1; 1H-NMR (300 MHz, DMSOd6): 2.32 (1H, dd, 2J 15.3, 3J 7.5 Hz, C5H), 2.50 (1H, dd, 2 J 15.3, 3J 6.2 Hz, C5H'), 4.69 (1H, t, 3J 6.5 Hz, C6H), 6.69 (2H, br s, NH2), 7.30 (4H, m, ArH), 7.76 (1H, br s, NH) ppm; 13C-NMR (75 MHz, DMSO-d6): 38.0, 51.2, 124.8, 126.0, 127.5, 130.5, 133.2, 144.4, 161.8, 176.0 ppm; Anal. Calcd (%) for C10H10ClN3O (223.66): C, 53.70; H, 4.51; N, 18.79. Found: C, 53.82; H, 4.66; N, 18.90.

rD

Fo

N

ot

Pe rs

The catalyst was prepared by a simple sonochemical method using a precursor mixture obtained from dispersion of raw multiwall CNTs (0.1 gr) and tetraethylorthotitanat (0.3 gr) into 200 mL acetone by ultrasonication. Sodium dodecyl sulfate (0.04 gr) as surface functionalizing agent was then added to the above mixture under strong magnetic stirring. Then, hydrolysis was initiated by adding deionized water (200 mL) into the resultant mixture. The produced solid was filtered and dried in a vacuum oven at 77oC for about 20 h. TiO2-CNTs nanocomposite powder was finally obtained after heating at 400oC in an oven under ambient temperature with a heating rate of 1oC/min for 30 minutes [30].

bu tio n

3.2. General Procedure for the Preparation of TiO2CNTs Nanocomposite Catalyst

tri

on al

Fig. (3). Recyclability of the TiO2-CNTs nanocatalyst for the synthesis of 4b.

is

U

se

O

2-Amino-6-(4-bromophenyl)-5,6-dihydro-4(3H)-pyrimidinone (4b) Yield: 0.257g (96%); White solid, M.P. 286288oC (lit. 289-290oC [23]); IR (KBr): 3355, 3200, 3025, 1628, 1579, 1500, 1399 cm-1; 1H-NMR (300 MHz, DMSOd6): 2.26 (1H, dd, 2J 15.3, 3J 7.7 Hz, C5H), 2.51 (1H, dd, 2 J 15.3, 3J 6.0 Hz, C5H'), 4.65 (1H, t, 3J 6.5 Hz, C6H), 6.65 (2H, br s, NH2), 7.25 (2H, d, 3J 8.0, C2'H, C6'H), 7.55 (2H, d, 3J 8.0, C3'H, C5'H), 7.70 (1H, br s, NH) ppm; 13C-NMR (75 MHz, DMSO-d6): 39.9, 52.9, 122.2, 130.0, 133.0, 143.0, 163.5, 177.4 ppm; Anal. Calcd (%) for C10H10BrN3O (268.11): C, 44.80; H, 3.76; N, 15.67. Found: C, 44.92; H, 3.91; N, 15.78.

3.3. General Procedure for the Synthesis of Compounds 4a-k Meldrum’s acid 1 (144 mg, 1 mmol), an aromatic aldehyde 2a-k (106 mg, 185 mg, 141 mg, 175 mg, 131 mg, 136 mg, 120 mg, 151 mg, 96 mg, 145 mg, 112 mg, 1 mmol), guanidine nitrate 3 (122 mg, 1 mmol), and TiO2-CNTs nanocomposite (24 mg, 15 mol %) were mixed together in a round bottom flask. The mixture was stirred at 80 ˚C for an appropriate time (see Table 2). After completion of the reaction as indicated by TLC (eluent: ethyl acetate/methanol = 10/1), the reaction mixture was poured into hot ethanol (3 mL) and then centrifuged for 5 min at 2000-3000 rpm to recover the catalyst. The recovered catalyst was then washed with EtOH for reuse after getting dried in air at ambient temperature for

2-Amino-6-(2,4-dichlorophenyl)-5,6-dihydro-4(3H)-pyrimidinone (4d) Yield: 0.232g (90%); White solid, M.P. 290291oC (lit. 294oC [23]); IR (KBr): 3355, 3120, 3085, 1633, 1579, 1545, 1497 cm-1; 1H-NMR (300 MHz, DMSO-d6): 2.21 (1H, dd, 2J 15.4, 3J 6.2 Hz, C5H), 2.64 (1H, dd, 2J 15.4, 3 J 6.7 Hz, C5H'), 4.94 (1H, br s, C6H), 6.73 (2H, br s, NH2), 7.31 (1H, br s, NH), 7.51 (3H, m, ArH) ppm; 13C-NMR (75 MHz, DMSO-d6): 36.5, 49.1, 128.3, 128.9, 129.6, 132.6, 133.3, 138.6, 162.5, 175.4 ppm; Anal. Calcd (%) for C10H9Cl2N3O (258.11): C, 46.54; H, 3.51; N, 16.28. Found: C, 46.67; H, 3.61; N, 16.17. 2-Amino-6-(4-cyanophenyl)-5,6-dihydro-4(3H)-pyrimidinone (4e) Yield: 0.205g (96%); White solid, M.P. 294296oC (lit. 297oC [23]); IR (KBr): 3350, 3050, 2195, 1644, 1570, 1540, 1498 cm-1; 1H-NMR (300 MHz, DMSO-d6): 2.27 (1H, dd, 2J 15.2, 3J 7.4 Hz, C5H), 2.55 (1H, dd, 2J 15.2, 3 J 6.3 Hz, C5H'), 4.77 (1H, br s, C6H), 6.62 (2H, br s, NH2), 7.49 (2H, d, 3J 7.7, C2'H, C6'H), 7.72 (1H, br s, NH), 7.84 (2H, d, 3J 7.9, C3'H, C5'H) ppm; 13C-NMR (75 MHz, DMSO-d6): 38.4, 51.9, 110.7, 119.2, 127.6, 133.0, 148.2,

366 Letters in Organic Chemistry, 2017, Vol. 14, No. 5

Khalilian et al.

2-Amino-6-(4-methoxyphenyl)-5,6-dihydro-4(3H)-pyrimidinone (4f) Yield: 0.206g (94%); White solid, M.P. 277278oC (lit. 278-279oC [23]); IR (KBr): 3360, 3350, 3030, 2825, 1629, 1552, 1501, 1374 cm-1; 1H-NMR (300 MHz, DMSO-d6): 2.27 (1H, dd, 2J 15.3, 3J 8.8 Hz, C5H), 2.55 (1H, dd, 2J 15.3, 3J 6.0 Hz, C5H'), 3.73 (3H, s, OCH3), 4.56 (1H, t, 3J 6.0 Hz, C6H), 6.47 (2H, br s, NH2), 6.91 (2H, d, 3J 8.6, C2'H, C6'H), 7.24 (2H, d, 3J 8.6, C3'H, C5'H), 7.54 (1H, br s, NH) ppm; 13C-NMR (75 MHz, DMSO-d6): 49.5, 53.2, 54.1, 112.0, 125.5, 131.7, 156.8, 160.0, 174.3 ppm; Anal. Calcd (%) for C11H13N3O2 (219.24: C, 60.26; H, 5.98; N, 19.17. Found: C, 60.36; H, 5.83; N, 19.09.

CONCLUSION In this research, 2-amino-6-aryl-5,6-dihydro-4(3H)-pyrimidinones were synthesized using a highly efficient procedure catalyzed by TiO2-CNTs nanocomposite. The simplicity of operation, use of non-toxic, low cost and recyclable catalyst, avoidance for using any harmful organic solvent, improved product yields, shorter reaction time, and solvent-free conditions are the unique merits of this new method compared to previous methods.

O

2-Amino-6-(4-methylphenyl)-5,6-dihydro-4(3H)-pyrimidinone (4g) Yield: 0.195g (96%); White solid, M.P. 270272oC (lit. 274-275oC [23]); IR (KBr): 3355, 3150, 3100, 1630, 1577,1486 cm-1. 1H-NMR (300 MHz, DMSO-d6): 2.26 (1H, m, C5H), 2.28 (3H, s, CH3), 2.46 (1H, m, C5H'), 4.58 (1H, t, 3J 7.1, C6H), 6.41 (2H, br s, NH2), 7.20 (4H, br s, ArH) 7.49 (1H, br s, NH) ppm; 13C-NMR (75 MHz, DMSOd6): 21.2, 39.1, 52.1, 126.5, 129.6, 137.3, 139.3, 162.4, 176.6 ppm; Anal. Calcd (%) for C11H13N3O (203.24): C, 65.01; H, 6.45; N, 20.68. Found: C, 65.09; H, 6.56; N, 20.90.

2-Amino-6-(2-thienyl)-5,6-dihydro-4(3H)-pyrimidinone (4k) Yield: 0.191g (98%); White solid, M.P. 276-277oC; IR (KBr): 3348, 3149, 3061, 1640, 1573, 1510, 1467 cm-1; 1HNMR (300 MHz, DMSO-d6): 2.20 (1H, dd, 2J 15.0, 3J 6.5 Hz, C5H), 2.56 (1H, dd, 2 J 15.0, 3J 6.2 Hz, C5H'), 4.74 (1H, t, 3J 6.5 Hz, C6H), 6.61 (2H, br s, NH2), 7.34 (3H, m, ArH), 7.74 (1H, br s, NH) ppm; 13C-NMR (75 MHz, DMSO-d6): 39.8, 52.8, 124.3, 129.9, 133.6, 140.0, 161.2, 177.3 ppm; Anal. Calcd (%) for C8H9N3OS (195.24): C, 49.22; H, 4.65; N, 21.52. Found: C, 49.31; H, 4.53; N, 21.62.

nl y

162.4, 175.7 ppm; Anal. Calcd (%) for C11H10N4O (214.23): C, 61.67; H, 4.71; N, 26.15. Found: C, 61.55; H, 4.58; N, 25.93.

tri

We are grateful to the East Tehran Branch Islamic Azad University Research Council for the financial support of this work. We also thank Young Researchers and Elite Club of East Tehran Branch, Islamic Azad University. REFERENCES [1]

[2]

[3]

[4]

N

ot

Fo

2-Amino-6-(2-furanyl)-5,6-dihydro-4(3H)-pyrimidinone (4i) Yield: 0.172g (96%); White solid, M.P. 268-270oC; IR (KBr): 3358, 3145, 3101, 1643, 1582, 1465, 1228 cm-1; 1HNMR (300 MHz, DMSO-d6): 2.25 (1H, dd, 2J 15.3, 3J 7.5 Hz, C5H), 2.48 (1H, dd, 2 J 15.3, 3J 6.0 Hz, C5H'), 4.57 (1H, t, 3J 7.0 Hz, C6H), 6.05 (1H, d, 3J 4.1, C4'H), 6.50 (2H, br s, NH2), 7.03 (1H, m, C5'H), 7.23 (1H, d, 3J 4.0, C3'H), 7.66 (1H, br s, NH) ppm; 13C-NMR (75 MHz, DMSO-d6): 38.6, 52.4, 108.2, 119.7, 144.8, 149.8, 163.6, 176.5 ppm; Anal. Calcd (%) for C8H9N3O2 (179.18): C, 53.63; H, 5.06; N, 23.45. Found: C, 53.79; H, 5.21; N, 23.37.

2-Amino-6-(1H-indol-3-yl)-5,6-dihydro-4(3H)-pyrimidinone (4j) Yield: 0.217g (95%); White solid, M.P. 252253oC; IR (KBr): 3328, 3281, 3036, 1665, 1564, 1472 cm-1; 1 H-NMR (300 MHz, DMSO-d6): 2.27 (1H, m, C5H), 2.50 (1H, m, C5H'), 4.59 (1H, br s, C6H), 6.44 (2H, br s, NH2), 6.89 (1H, s, C2'H), 7.06 (1H, d, 3J 6.9, C7'H), 7.31 (2H, m, C5'H, C6'H), 7.57 (1H, br s, N3'H), 7.80 (1H, m, C4'H), 8.20 (1H, br s, NH) ppm; 13C-NMR (75 MHz, DMSO-d6): 40.3, 50.7, 108.8, 113.1, 118.7, 122.6, 123.6, 129.1, 139.7, 148.8, 160.9, 176.4 ppm; Anal. Calcd (%) for C12H12N4O (228.25): C, 63.15; H, 5.30; N, 24.55. Found: C, 62.95; H, 5.12; N, 24.32.

bu tio n

ACKNOWLEDGEMENTS

rD

Pe rs

on al

2-Amino-6-(3-nitrophenyl)-5,6-dihydro-4(3H)-pyrimidinone (4h) Yield: 0.218g (93%); White solid, M.P. 255257oC (lit. 258˚C [23]); IR (KBr): 3395, 3230, 3120, 1634, 1577, 1515, 1437 cm-1; 1H-NMR (300 MHz, DMSO-d6): 2.33 (1H, dd, 2J 15.5, 3J 7.6 Hz, C5H), 2.62 (1H, dd, 2J 15.5, 3 J 6.1 Hz, C5H'), 4.85 (1H, br s, C6H), 6.70 (2H, br s, NH2), 7.67 (1H, t, 3J 7.9, C5'H), 7.77 (1H, s, C2'H), 7.79 (1H, d, 3J 7.5, C6'H), 8.15 (1H, d, 3J 8.0, C4'H), 8.17 (1H, br s, NH) ppm; 13C-NMR (75 MHz, DMSO-d6): 38.4, 51.6, 121.1, 122.9, 130.6, 133.5, 144.8, 148.3, 162.3, 176.0 ppm; Anal. Calcd (%) for C10H10N4O3 (234.21): C, 51.28; H, 4.30; N, 23.22. Found: C, 51.14; H, 4.10; N, 23.41.

The author(s) confirm that this article content has no conflict of interest.

is

U

se

CONFLICT OF INTEREST

[5] [6]

[7]

[8]

[9]

Burda, C.; Chen, X.B.; Narayanan, R.; El-Sayed, M.A. Chemistry and properties of nanocrystals of different shapes. Chem. Rev., 2005, 105(4), 1025-1102. Kim, A.Y.; Lee, H.J.; Park, J.C.; Kang, H.; Yang, H.; Song, H.; Park, K.H. Highly efficient and reusable copper-catalyzed Narylation of nitrogen-containing heterocycles with aryl halides. Molecules, 2009, 14(12), 5169-5178. Lin, K.S.; Pan, C.Y.; Chowdhury, S.; Tu, M.T.; Hong, W.T.; Yeh, C.T. Hydrogen generation using a CuO/ZnO-ZrO2 nanocatalyst for autothermal reforming of methanol in a microchannel reactor. Molecules, 2011, 16(1), 348-366. Monopoli, A.; Nacci, A.; Caló, V.; Ciminale, F.; Cotugno, P.; Mangone, A.; Giannossa, L.C.; Azzone, P.; Cioffi, N. Palladium/ zirconium oxide nanocomposite as a highly recyclable catalyst for C-C coupling reactions in water. Molecules, 2010, 15(7), 45114525. Kantam, M.L.; Laha, S.; Yadav, J.; Sreedhar, B. Friedel-Crafts alkylation of indoles with epoxides catalyzed by nanocrystalline titanium(IV) oxide. Tetrahedron Lett., 2006, 47(35), 6213-6216. Hosseini-Sarvari, M. Titania (TiO2)-catalyzed expedient, solventless and mild synthesis of bis(indolyl)methanes. Acta. Chim. Slov., 2007, 54(2), 354-359. Ropero-Vega, J.L.; Aldana-Péreza, A.; Gómez, R.; Niño-Gómez, M.E. Sulfated titania [TiO2 /SO 42-]: A very active solid acid catalyst for the esterification of free fatty acids with ethanol. Appl. Catal. Gen., 2010, 379(1-2), 24-29. Kassaee, M.Z.; Mohammadi, R.; Masrouri, H.; Movahedi, F. Nano TiO2 as a heterogeneous catalyst in an efficient one-pot threecomponent Mannich synthesis of β-aminocarbonyls. Chin. Chem. Lett., 2011, 22(10), 1203-1206. Shirini, F.; Alipour Khoshdel, M.; Abedini, M.; Atghia, S.V. Nanocrystalline TiO2 as an efficient and reusable catalyst for the chemoselective trimethylsilylation of primary and secondary alcohols and phenols. Chin. Chem. Lett., 2011, 22(10), 1211-1214.

An Eco-Friendly and Highly Efficient Synthesis of Pyrimidinones

[16]

[17] [18]

[19]

Pe rs

[21]

on al

U

[20]

[26]

[27]

[28]

[29]

[30]

bu tio n

[15]

[25]

nl y

[14]

[24]

tri

[13]

[23]

O

[12]

[22]

367

the sponge Batzella sp.: Inhibitors of HIV gp120-human CD4 binding. J. Org. Chem., 1995, 60(5), 1182-1188. Ostras, K.S.; Gorobets, N.Y.; Desenko, S.M.; Musatov, V.I. An easy access to 2-amino-5,6-dihydro-3H-pyrimidin-4-one building blocks: the reaction under conventional and microwave conditions. Mol. Divers., 2006, 10(2), 483-489. Mohammadnejad, M.; Hashtroudi, M.S.; Balalaie, S. Efficient synthesis of 2-amino-6-aryl-5,6-Dihydro-3H-pyrimidin-4-one building blocks via Domino reaction. Heterocycl. Commun., 2009, 15(6), 459-466. Mirza-Aghayan, M.; Baie Lashaki, T.; Rahimifard, M.; Boukherroub, R.; Tarlani, A.A. Amino-functionalized MCM-41 base-catalyzed one-pot synthesis of 2-amino-5,6-dihydropyrimidin4(3H)-ones. J. Iran. Chem. Soc., 2011, 8(1), 280-286. Abdolmohammadi, S.; Afsharpour, M.; Keshavarz-Fatideh, S. An efficient green synthesis of 3-amino-1H-chromenes catalysed by ZnO nanoparticles thin-film. S. Afr. J. Chem.-S. Afr. T., 2014, 67, 203-210. Abdolmohammadi, S.; Afsharpour, M. An operationally simple green procedure for the synthesis of dihydropyrimido[4,5-d] pyrimidinetriones using CuI nanoparticles as a highly efficient catalyst. Z. Naturforsch., 2015, 70b(3), 171-176. Abdolmohammadi, S.; Aghaei-Meybodi, Z. Simple and efficient route toward ambient preparation of pyrimido[b]quinolinetriones using copper (I) iodide nanoparticles in aqueous media. Comb. Chem. High T. Scr., 2015, 18(9), 911-916. Abdolmohammadi, S.; Karimpour, S. Rapid and mild synthesis of quinazolinones and chromeno[d]pyrimidinones using nanocrystalline copper(I) iodide under solvent-free conditions. Chin. Chem. Lett., 2016, 27(1), 114-118. Abdolmohammadi, S.; Ghiasi, R.; Ahmadzadeh-Vatani, S. A highly efficient CuI nanoparticles catalyzed synthesis of tetrahydrochromenediones and dihydropyrano[c]chromenediones under grinding. Z. Naturforsch., 2016, 71b(7), 777-782. Khosravifard, E.; Salavati-Niasari, M.; Dadkhah, M.; Sodeifian, Gh. Synthesis and characterization of TiO 2-CNTs nanocomposite and investigation of viscosity and thermal conductivity of a new nanofluid. J. Nanostruct., 2012, 2(2), 191-197.

is

[11]

Shirini, F.; Atghia, S.V.; Alipour, K.M. Nanocrystalline TiO2 as an efficient and reusable catalyst for the one-pot synthesis of polyhydroquinolien derivatives via Hantzsch reaction. Iranian J. Catal., 2011, 1(2), 93-97. Sajadi, S.M.; Naderi, M.; Babadoust, S. Nano TiO2 as an efficient and reusable heterogeneous catalyst for the synthesis of 5substituted 1H-tetrazoles. Nat. Sci. Res., 2011, 1(3), 10-17. Abdolmohammadi, S. TiO2 nanoparticles as an effective catalyst for the synthesis of hexahydro-2-quinolinecarboxylic acids derivatives. Chin. Chem. Lett., 2012, 23(9), 1003-1006. Abdolmohammadi, S. Simple route to indeno[1,2-b]quinoline derivatives via a coupling reaction catalyzed by TiO2 nanoparticles. Chin. Chem. Lett., 2013, 24(4), 318-320. Abdolmohammadi, S.; Mohammadnejad, M.; Shafaei, F. TiO2 nanoparticles as an efficient catalyst for the one-pot preparation of tetrahydrobenzo[c]acridines in aqueous media. Z. Naturforsch., 2013, 68b(4), 362-366. Iijima, S. Helical microtubules of graphitic carbon. Nature, 1991, 354(6348), 56-58. Auer, E.; Freund, A.; Pietsch, J.; Tacke, T. Carbons as supports for industrial precious metal catalysts. Appl. Catal. A, 1998, 173(2), 259-271. Woan, K.; Pyrgiotakis, G.; Sigmund, W. Photocatalytic carbonnanotube-TiO2 composites. Adv. Mater., 2009, 21(21), 2233-2239. Safari, J.; Gandomi-Ravandi, S. Carbon nanotubes supported by titanium dioxide nanoparticles as recyclable and green catalyst for mild synthesis of dihydropyrimidinones/thiones. J. Mol. Struct., 2014, 1065, 241-247. Kappe, C.O. 100 years of the Biginelli dihydropyrimidine synthesis. Tetrahedron, 1993, 49(32), 6937-6963. Rovnyak, G.C.; Kimball, S.D.; Beyer, B.; Cucinotta, G.; DiMarco, J.D.; Gougoutas, J.; Hedberg, A.; Malley, M.; McCarthy, J.P. Calcium entry blockers and activators: Conformational and structural determinants of dihydropyrimidine calcium channel modulators. J. Med. Chem., 1995, 38(1), 119-129. Patil, A.D.; Kumar, N.V.; Kokke, W.C.; Bean, M.F.; Freyer, A.J.; De Brosse, C.; Mai, S.; Truneh, A.; Carte, B. Novel alkaloids from

se

[10]

Letters in Organic Chemistry, 2017, Vol. 14, No. 5

N

ot

Fo

rD

DISCLAIMER: The above article has been published in Epub (ahead of print) on the basis of the materials provided by the author. The Editorial Department reserves the right to make minor modifications for further improvement of the manuscript.