RESEARCH LETTER A green synthesis of 3,4-dihydropyrimidin-2-ones and 1,5-benzodiazepines catalyzed by Sn(HPO4)2.

H2O nanodisks under solvent-free condition at room temperature

Parasa Hazarika, Pranjal Gogoi, Sangeeta Hatibaruah and Dilip Konwar*
Synthetic Organic Chemistry Division, North East Institute of Science and Technology (a constituent establishment of CSIR, India), Jorhat 785006, Assam, India (Received 24 March 2010; final version received 10 March 2011) Heterogeneous Tin (IV) hydrogen phosphate nanodisks [Sn(HPO4)2.H2O] efficiently catalyzed the one-pot three component condensation of aromatic aldehydes, b-ketoesters and urea to produce 3,4dihydropyrimidin-2-ones under solvent-free conditions at room temperature. Also, the catalyst is equally applicable for the preparation of 1,5benzodiazepines under the same reaction conditions. The optimum load of the catalyst required is 10 mole% and reusable. Hence, the process is green.

O R H + H2N

X NH2 + R

O Sn(HPO4)2.H2O R Neat, R.T. R R2

R1 NH N H X

NH2

Sn (HPO4)2.H2O
CH2R5

H N

R4

R5 R5

+
NH2

2 R4

Neat, R.T.

R4

Keywords: Sn(HPO4)2.H2O nanodisks; 3,4-dihydropyrimidin-2-ones; 1,5-heterogeneous catalyst; solventfree condition

Introduction The development of green technology has received tremendous attention from chemists due to conservation of global eco-system (1). In this context, the development of new catalysts that are environmentally benign and effective are of great interests. Nanomaterials (24) with larger surface area and high density active sites to those of bulk materials have gained much interest in the field of chemistry for their catalytic properties in many important organic reactions. And, the reactions conducted under solvent-free conditions using reusable nano-catalysts (5 7) is now become a trust area of research in developing environmentally benign technology. In this endeavor, organic group transformation reac-

tions using nanoparticles in organic solvents, for example, Ni (8), Cu (9), Ag (10), polysilane-supported Pd and Pt nanoparticles (11), RuO2-FAU nanoclusters (12), optically active bisphosphine (BINAP) stabilized Pd (13) are reported. On the other hand, green synthesis of chiral (14) or achiral compounds through multicomponent reactions (MCRs) (1517) reactions covers a major area of research in recent years. Multicomponent Biginelli reaction (18) offers an efficient route to access 3,4-dihydropyrimidin-2-ones (DHPMs) that show a wide range of important pharmacological properties like calcium channel blockers, antihypertensive agents, a-1a antagonist, neuropeptide Y (NPY) antagonists, anticancer drugs, and so on and alkaloids containing dihydropyrimidinone moiety

*Corresponding author. Email: dkonwar@yahoo.co.uk

ISSN 1751-8253 print/ISSN 1751-7192 online # 2011 Taylor & Francis DOI: 10.1080/17518253.2011.571719 http://www.informaworld.com

P. Hazarika et al.
O Sn(HPO 4)2.H2O R2 3 R3 Neat, R.T. R3 1 2 N H 4 X R2 R1 NH

O R1 H + H2N

X NH2 +

R1 = aryl, heterocyclic, R 2 = CH 3, R3 = OCH3, OC2H5 X = O, S

Scheme 1. Synthesis of 3,4-dihydropyrimidin-2-ones.

particularly the batzelladine alkaloids are potent HIVgp-120-CD4 inhibitors (1922). Dihydropyrimidinones (DHPMs) scaffolds are synthesized by several improved protocols that involve bulk catalysts viz. Lewis and Brnsted acid catalysts (2328), polymer supported reagents (29, 30), microwave-assisted methodologies (31), grinding techniques (32), and ultrasonic methods (33) in organic solvents. Recently, solvent-free conditions using Yb(OTf)3 (34), montmorillonite (35), and ionic liquid (36) as catalysts are reported where bulk amount of catalysts or rare earth metals are involved. In continuation of our efforts toward the development of green synthetic methodologies (3741) and nano materials (42), we now wish to report herein a highly efficient, green, and recyclable Tin (IV) hydrogen phosphate [Sn(HPO4)2.H2O] nanodisks (43) as heterogeneous catalyst for the synthesis of

DHPMs under solvent-free condition at room temperature (Scheme 1). Results and discussion Initially, the one pot experiment of the Biginelli condensation was carried out with benzaldehyde, ethylacetoacetate, and urea catalyzed by Sn(HPO4)2.H2O nanodisks under solvent-free condition at room temperature. The optimum reaction condition was screened by using different catalyst loading under solvent-free conditions at room temperature and it was found that 10 mol% of the catalyst was the optimum load for the highest formation of DHPMs in the reaction mixture (Table 1, entry 3). An increase in the amount of the catalyst loading from 10 to 20 mol% gave almost the same yield of the product (Table 1). Having optimized the

Table 1. Synthesis of dihydropyrimidin-2(1H)-ones catalyzed by Sn(HPO4)2.H2O nanodisks with different catalyst loadings under solvent-free condition.

CHO O + O OEt + H2N O NH2 Sn(HPO4)2.H2O EtO Neat, R.T.

O NH N H O

Me

Entry 1 2 3 4 5
a

Reaction media Neat Neat Neat Neat Neat

Catalyst load (mol%) 3 5 10 15 20

Time (h) 2 2.5 1 1 1

Yield (%)a 80 85 97 97 96

Isolated yield.

0.80 0.80 n8-19 n21 a7

Green Chemistry Letters and Reviews

Table 2. Synthesis of dihydropyrimidin-2(1H)-ones and thiones catalyzed by Sn(HPO4)2.H2O nanodisks under solvent-free condition at room temperature. Entry 1 2 3 4 5 6 7 8 9
O

R1 C6H5 4(CH3O)C6H4 4(NO2)C6H4 4(Cl)C6H4 2,4(Cl)2C6H3 3(OH)C6H4 C6H5CH CH (CH3)2CH

R2 C2H5O C2H5O C2H5O C2H5O C2H5O C2H5O C2H5O C2H5O C2H5O

R3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3

X O O O O O O O O O O O O S S S

Time(h) 0.75 1.2 0.5 0.6 0.7 1.5 1.8 2.1 1.8 0.8 1.3 0.6 1.0 1.4 0.8

Yielda(%) 96 92 95 94 93 90 88 86 84 96 92 95 95 90 93

10 11 12 13 14 15
a b

C6H5 4(CH3O)C6H4 4(NO2)C6H4 C6H5 4(CH3O)C6H4 4(Cl)C6H4

CH3O CH3O CH3O C2H5O C2H5O C2H5O

Isolated yield, stirring at 25308C. The structures of all the compounds were determined by using 1H NMR, FT-IR, MS (m/z), and elemental analyses and they are in good agreement with the authentic samples (1720).

reaction conditions, a wide range of structurally varied aldehydes, b-ketoesters, and urea were coupled together by this protocol to produce the corresponding dihydropyrimidinones. The electronic variation (electron withdrawing and donating groups) on aryl aldehydes caused no appreciable change in the efficiency of the condensation. Thiourea was used with similar success to produce the corresponding dihydropyrimidin-2-thiones (Table 2, entries 1315) that are also of much important with regard to
Table 3. Recycling of Sn(HPO4)2.H2O nanodisks catalyst.

biological activity (44). The catalyst was recovered quantitatively from the reaction mixture by simple filtration. After washed with ethanol (2  5 ml), it was dried in an oven at 608C for 1 hour and reused for five consecutive times without loss of catalytic activity (Table 3). Having successfully established the methodology for the DHPMs scaffold, we were keen to explore the efficiency of the catalyst for the condensation of o-phenylenediamine with a ketone having an

CHO O + O OEt + H2N O NH2 Sn(HPO4)2.H2O EtO Neat, R.T.

O NH N H O

Me

Entry 1 2 3 4 5
a b

No. of run First run Second run Third run Fourth run Fifth run

Time (h) 0.75 0.75 0.75 0.75 0.75

Conversionb (%) 97 96 94 93 90

Yielda (%) 96 95 95 94 92

Isolated yield. Determined by GC.

P. Hazarika et al.
H N R4 R5 R5 R4 CH2R5

NH2

Sn (HPO4)2.H2O Neat, R.T.

+
NH2

2 N

R4

R4 = alkyl, aryl, R5 = H, alkyl

Scheme 2. Synthesis of 1, 5-benzodiazepines.

a-hydrogen under solvent-free conditions at room temperature (Scheme 2) and gratifyingly, the respective 1,5-benzodiazepines (4549) were produced with excellent yields (Table 4). The scope of the protocol was examined with o-phenylenediamine

and different aliphatic (acyclic and cyclic) and aromatic ketones and it formed 1,5-benzodiazepines in excellent yields within 1.22 hours using 10 mol% of the catalyst under the same reaction conditions.

0.80 3.80 n2,3,4,6 a1 n1

Table 4. Synthesis of 1,5-benzodiazepines catalyzed by Sn(HPO4)2.H2O nanodisks under solvent-free condition at room temperature. Entry Diamine Ketone Product
H N

Time (h)

Yielda (%)

NH2

1
NH2

CH3COCH3
N

1.2

95

n2

NH2

2
NH2

CH3CH2COCH2CH3

H N

1.4

93

n3

NH2

H N

3
NH2

CH3COCH2CH3
N
Ph

1.3

92

NH2

H N

n4

4
NH2

PhCOCH3
N Ph

1.8

94

NH2

H N

5
NH2 NH2

CH3COCH2 CH(CH3) CH3

N
O

1.6

90

n6

H N

6
NH2
a

2.0
N

88

Isolated yield; stirring at 25308C. The structures of all the compounds were determined by using 1H NMR, FT-IR, MS (m/z), and elemental analyses and they are in good agreement with the authentic samples (4347).

Green Chemistry Letters and Reviews Experimental All reagents were obtained from commercial sources and used without further purification. The solvents for chromatography were distilled before use. Melting points were measured using Buchi B-540 apparatus and are uncorrected. 1H NMR spectra were recorded on Avance DPX 300 MHz FT-NMR spectrometer. Chemical shifts are expressed in ^ units relative to tetramethylsilane (TMS) signal as internal reference in DMSO-d6 or CDCl3. The Fourier transform-infra red (FT-IR) spectra were recorded on FT-IR-system-2000 Perkin Elmer spectrometer in CHCl3 or on KBr pellets. The SEM was recorded by Scanning Electron Microscope Model: JEOL JSM6390LV. The X-ray diffraction (XRD) patterns were recorded on a Rigaku Miniflex diffractometer with ). monochromatized Cu Ka radiation (l  1.5418 A Gas chromatography (GC) analysis was performed on the Chemito GC 1000 spectrometer.

(M); Anal. Calcd. for C14H16O3N2: C, 64.60; H, 6.20; N, 10.76. Found: C, 64.56; H, 6.14; N, 10.74.

5-(Ethoxycarbonyl)-6-methyl-4-(4-methoxyphenyl)3,4-dihydropyrimidin-2(1H)-thione (Table 2, entry 14) M.P. 1501518C; 1H NMR (DMSO, 300 MHz): ^ 1.09 (t, 3H), 2.26 (s, 3H), 3.72 (s, 3H), 3.99 (q, 2H), 5.11 (s, 1H), 6.887.16 (m, 4H), 9.49 (s, 1H), 10.21 (s, 1H); FT-IR (KBr, cm1): 1561.4, 1599.0, 1651.2, 3250.8; MS (m/z): 306.32 (M); Anal. Calcd. For C15H18O3N2S: C, 58.80; H, 5.92; N, 9.14. Found: C, 58.74; H, 5.97; N, 9.19.

4.30 1.60 n20 a7

0.80 4.50 n7

General procedure for the synthesis of 3, 4-dihydropyrimidin-2-ones In a 50 ml round-bottom flask, aldehyde (2 mmol), ethyl aetoaetate (2 mmol), and urea (3 mmol) were stirred in presence of Sn(HPO4)2.H2O nanodisks (43) (10 mol%) under solvent-free condition at room temperature for the stipulated time. The progress of the reaction was monitored by TLC. After completion of the reaction, methanol was added to dissolve the solid formed and the catalyst was filtered off, the filtrate was concentrated in vacuum and recrystallized from ethanol to afford pure product. General procedure for the synthesis of 1, 5-benzodiazepines In a 50 ml round-bottom flask, o-phenylenediamines (1mmol) and ketones (2.2 mmol) were stirred in presence of Sn(HPO4)2.H2O nanodisks (10 mol%) under solvent-free condition at the room temperature. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added, catalyst was filtered off, and the products were purified by column chromatography on silica gel (60120 mesh) using ethyl acetate/hexane mixture as eluent to afford pure 1, 5-benzodiazepines.

2-Methyl-2,4-diisobutyl-2,3-dihydro-1H-1,5-benzodiazepine (Table 4, entry 5) M.P. 1181208C; 1H NMR (CDCl3, 300 MHz): ^ 0.951.05 (m, 12H), 1.33 (s, 3H), 1.491.52 (m, 2H), 1.651.75 (m, 1H), 2.052.25 (m, 3H), 2.24 (d, 2H), 6.606.65 (m, 1H), 6.856.95 (m, 2H), 7.057.15 (m, 1H); FT-IR (KBr, cm1): 3330.7, 1637.5; MS (m/z): 272.32 (M); Anal. Calcd. For C18H28N2: C, 79.36; H, 10.36; N, 10.28. Found: C, 79.27; H, 10.23; N, 10.19. Conclusion The catalytic activity of Sn(HPO4)2.H2O nanodisks as a heterogeneous catalyst for the synthesis of 3,4dihydropyrimidin-2-ones under solvent-free condition at room temperature was investigated. Also, the catalyst was found to be equally effective for the synthesis of 1,5-benzodiazepines. The nanodisks behave as a Brnsted acid under the reaction conditions. Also, the catalyst is reusable, the reaction is multicomponent one pot synthesis under solvent-free conditions and, hence, it is green.

4.30 3.50 n5 a1

0.80 6.70 n1

Acknowledgements
The authors thank the Director, Dr. P.G. Rao, HOD, Dr. J.C.S. Kataky, Synthetic Organic Chemistry Division and the Analytical Division of NEIST, Jorhat, Assam, India, for their help. P.H. thanks CSIR, New Delhi, for the research fellowship.

n7

5-(Ethoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (Table 2, entry 1) M.P. 2022038C; 1H NMR (DMSO, 300 MHz): ^ 1.08 (t, 3H), 2.23 (s, 3H), 3.98 (q, 2H), 5.13 (d, 1H), 7.107.29 (m, 5H), 7.81 (s, 1H), 9.15 (s, 1H); FT-IR (KBr, cm1): 1635.2, 1725.1, 3240.5; MS (m/z): 260.26

Supporting information All the products were fully characterized by 1H and 13 C NMR and MS analyses. The experimental procedures and spectral data of the compounds are available in the Supporting Information (Appendix 1).

P. Hazarika et al.
(24) Ranu, B.C.; Hajra, A.; Jana, U. J. Org. Chem. 2000, 65, 6270. (25) Bose, D.S.; Fatima, L.; Mereyala, H.B. J. Org. Chem. 2003, 68, 587. (26) Wang, Z.-T.; Xu, L.-W.; Xia, C.-G.; Wang, H.-Q. Tetrahedron Lett. 2004, 45, 7951. (27) Heravi, M.M.; Bakhtiari, K.; Bamoharram, F.F. Catal. Commun. 2006, 7, 373. (28) Debache, A.; Boumoud, B.; Amimour, M.; Belfaitah, A.; Rhouati, S.; Carboni, B. Tetrahedron Lett. 2006, 47, 5697. (29) Dondoni, A.; Massi, A. Tetrahedron Lett. 2004, 42, 7975. (30) Palaniappan, S.; John, A. J. Mol. Catal. A: Chem. 2005, 233, 9. (31) Gohain, M.; Prajapati, D.; Sandhu, J.S. Synlett. 2004, 235. (32) Ranu, B.C.; Hajra, A.; Dey, S.S. Org. Process Res. Develop. 2002, 6, 817. (33) Zhang, X.; Li, Y.; Liu, C.; Wang, J. J. Mol. Catal. A: Chem. 2006, 253, 207. (34) Ma, Y.; Qian, C.; Wang, L.; Yang, M. J. Org. Chem. 2000, 65, 3864. (35) Bigi, F.; Carloni, S.; Frullanti, B.; Maggi, R.; Sartori, G. Tetrahedron Lett. 1999, 40, 3465. (36) Peng, J.; Deng, Y. Tetrahedron Lett. 2001, 42, 5917. (37) Gogoi, P.; Sarmah, G.K.; Konwar, D. J. Org. Chem. 2004, 69, 5153. (38) Gogoi, P.; Hazarika, P.; Konwar, D. J. Org. Chem. 2005, 70, 1934. (39) Das Sharma, S.; Gogoi, P.; Konwar, D. Green Chem. 2007, 9, 153. (40) Gogoi, P.; Konwar, D. Tetrahedron Lett. 2006, 47, 79. (41) Gogoi, P.; Konwar, D. Org. Biomol. Chem. 2005, 3, 3473. (42) Hazarika, P.; Das Sharma, S.; Konwar, D. Catal. Commun. 2008, 9, 2398. (43) Qiao, H.; Jia, F.; Ai, Z.; Li, Z.; Zhang, L. Chem. Commun. 2006, 2033. (44) Kappe, C.O. Tetrahedron, 1993, 49, 6937. (45) Schutz, H. Benzodiazepines; Springer: Weinheim, Germany, 1982; Vol. 2, p 240. (46) Sternbach, L.H. J. Med. Chem. 1979, 22, 1. (47) Ro mer, D.; Bu scher, H.H.; Hill, R.C.; Maurer, R.; Petcher, T.J.; Zeugner, R.H.; Benson, W.; Finner, E.; Milkowski Thies, W.P.W. Nature 1982, 298, 759. (48) Merluzzi, V.J.; Hargrave, K.D.; Labadia, M.; Grozinger, K.; Skoog, M.; Wu, J.C.; Shih, C.K.; Eckner, K.; Hattox, S.; Adams, J. Science 1990, 250, 411. (49) Hazarika, P.; Gogoi, P.; Konwar, D. Syn. Commun. 2007, 37, 3447.

References
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Green Chemistry Letters and Reviews Appendix 1: Supporting information

Experimental part

General information All reagents were obtained from commercial sources and used without further purification. The solvents for chromatography were distilled before use. Melting points were measured using Buchi B-540 apparatus and are uncorrected. 1H NMR spectra were recorded on Avance DPX 300 MHz FT-NMR spectrometer. Chemical shifts are expressed in ^ units relative to tetramethylsilane (TMS) signal as internal reference in DMSO-d6 or CDCl3. FT-IR spectra were recorded on FT-IR-system2000 Perkin Elmer spectrometer in CHCl3 or on KBr pellets. SEM was recorded by Scanning Electron Microscope model JEOL JSM-6390LV. X-ray diffraction (XRD) patterns were recorded on a Rigaku Miniflex diffractometer with ). Gas chromatography (GC) analysis was performed on Chemito GC monochromatized Cu Ka radiation (l  1.5418 A 1000 Spectrometer. Preparation of Sn(HPO4)2.H2O nanodisks Sn(HPO4)2.H2O nanodisks were prepared by following the published procedure (1). H3PO4 (85%) (0.3 ml) was added to a solution of 0.35g of SnCl4.5H2O (AR) in anhydrous ethanol (12 ml). The resulting reaction mixture was transferred to a 22 ml teflon-sealed autoclave and stored at 1808C for 24 hours, then air-cooled to room temperature. The product was washed several times with anhydrous ethanol and finally dried at 608C in a vacuum oven. The catalyst was characterized by SEM, XRD, and FT-IR analyses. Reference 1. Qiao, H.; Jia, F.; Ai, Z.; Li, Z.; Zhang, L. Chem. Commun. 2006, 2033. General procedure for the formation of 3,4-dihydropyrimidin-2-ones: In a 50 ml round-bottom flask, aldehyde (2 mmol), ethyl aetoacetate (2 mmol) and urea (3 mmol) were stirred in presence of Sn(HPO4)2.H2O nanodisks (10 mol%) under solvent-free condition at room temperature for the stipulated time. The progress of the reaction was monitored by TLC. After completion of the reaction, methanol was added to dissolve the solid formed and the catalyst was filtered off, the filtrate was concentrated in vacuum and recrystallized from ethanol to afford pure product. Spectral data of the 3,4-dihydropyrimidin-2-ones and thiones obtained by the condensation of aldehydes,1,3-dicarbonyls and urea/ thiourea 5-(Ethoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (Table 2, entry 1)

O EtO Me N H NH O

M.P. 2022038C; 1H NMR (DMSO, 300 MHz): ^1.08 (t, 3H), 2.23 (s, 3H), 3.98 (q, 2H), 5.13 (d, 1H), 7.107.29 (m, 5H), 7.81 (s, 1H), 9.15 (s, 1H); FT-IR (KBr, cm1): 1635.2, 1725.1, 3240.5; MS (m/z): 260.26 (M); Anal. Calcd. for C14H16O3N2:C, 64.60; H, 6.20; N, 10.76. Found: C, 64.56; H, 6.14; N, 10.74.

P. Hazarika et al.

5-(ethoxycarbonyl)-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (Table 2, entry 2)

OMe

O EtO Me N H NH O

M.P. 2002018C; 1H NMR (DMSO, 300 MHz): ^1.10 (t, 3H), 2.25 (s, 3H), 3.73 (s, 3H), 3.98 (q, 2H), 5.16 (s, 1H), 7.017.21 (m, 4H), 7.73 (s, 1H), 9.19 (s, 1H); FT-IR (KBr, cm1): 1635.7, 1717.5, 3242.1; MS (m/z): 290.39 (M); Anal. Calcd. for C15H18O4N2:C, 62.06; H, 6.25; N, 9.65. Found: C, 62.11; H, 6.16; N, 9.72. 5-(ethoxycarbonyl)-6-methyl-4-(4-nitrophenyl)-3,4-dihydropyrimidin-2(1H)-one (Table 2, entry 3)
NO2

O EtO Me N H NH O

M.P. 2082098C; 1H NMR (DMSO, 300 MHz): ^1.09 (t, 3H), 2.24 (s, 3H), 3.76 (q, 2H), 5.19 (d, 1H), 7.628.10 (m, 4H), 7.92 (s, 1H), 9.28 (s, 1H); FT-IR (KBr, cm1): 1644.2, 1723.6, 3240.0; MS(m/z): 305.20 (M); Anal. Calcd. for C14H15O5N3:C, 55.08; H, 4.95; N, 13.76. Found: C, 55.17; H, 4.88; N, 13.62. 5-(ethoxycarbonyl)-6-methyl-4-(4-chlorophenyl)-3,4-dihydropyrimidin-2(1H)-one (Table 2, entry 4)
Cl

O EtO Me N H NH O

M.P. 2102118C; 1H NMR (DMSO, 300 MHz): ^1.10 (t, 3H), 2.25 (s, 3H), 3.89 (q, 2H), 5.16 (s, 1H), 7.317.50 (m, 4H), 7.80 (s, 1H), 9.25 (s, 1H); FT-IR (KBr, cm1): 1644.0, 1723.1, 3239.7; MS(m/z): 294.79 (M); Anal. Calcd. for C14H15O3N2Cl:C, 57.05; H, 5.13; N, 9.50. Found: C, 57.12; H, 5.04; N, 9.45.

Green Chemistry Letters and Reviews

5-(ethoxycarbonyl)-4-(2,4-dichlorophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (Table 2, entry 5)
Cl

O EtO Me N H NH

Cl

M.P. 2382408C; 1H NMR (DMSO, 300 MHz): ^1.00 (t, 3H), 2.29 (s, 3H,), 3.90 (q, 2H), 5.60 (s, 1H), 7.32 (d, 1H), 7.42 (d, 1H), 7.57 ((s, 1H), 7.77 (s, 1H), 9.33 (s, 1H); FT-IR (KBr, cm1): 1635, 1697, 3357; MS (m/z): 328.80 (M); Anal. Calcd. For C14H14O3N2Cl2:C, 51.09; H, 4.25; N, 8.51; Found: C, 51.12; H, 4.21; N, 8.52. 5-(ethoxycarbonyl)-4-(3-hydroxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (Table 2, entry 6)
OH

O EtO Me N H NH O

M.P. 1631648C; 1H NMR (DMSO, 300 MHz): ^1.09 (t, 3H), 2.22 (s, 3H), 4.01 (q, 2H), 5.05 (d, 1H), 6.6 (s, 1H), 6.517.06 (m, 4H), 7.71 (s, 1H), 9.17 (s, 1H), 9.36 (s, 1H); FT-IR (KBr, cm1): 1644.2, 1723.6, 3240.0; MS (m/z): 276.23 (M); Anal. Calcd. For C14H16O4N2:C, 60.86; H, 5.84; N, 10.14. Found: C, 60.79; H, 5.88; N, 10.10. 5-(ethoxycarbonyl)-6-methyl-4-styryl-3,4-dihydropyrimidin-2(1H)-one (Table 2, entry 7)

CH O EtO Me N H CH NH O

M.P. 2322358C; 1H NMR (DMSO, 300 MHz): ^1.20 (t, 3H), 2.21 (s, 3H), 4.09 (m, 2H), 4.74 (d, 1H), 6.20 (dd, 1H), 6.37 (d, 1H), 7.217.46 (m, 5H), 7.53 (d, 1H), 9.13 (s, 1H); MS (m/z): 286.27 (M); Anal. Calcd. for C16H18O3N2:C, 67.12; H, 6.33; N, 9.78; Found: C, 67.09; H, 6.35; N, 9.75.

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5-(ethoxycarbonyl)-4-(iso-propyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (Table 2, entry 8)

O EtO Me N H CH(CH3)2 NH O

M.P. 1701718C; 1H NMR (DMSO, 300 MHz): ^0.760.81 (m, 6H), 1.07 (t, 3H), 1.69 (m, 1H), 2.19 (s, 3H), 4.02 (q, 2H), 4.89 (s, 1H), 7.54 (s, 1H), 9.00 (s, 1H); FT-IR (KBr, cm1): 1642.0, 1709.5, 3235.0; MS (m/z): 226.21 (M); Anal. Calcd. for C11H18O3N2:C, 58.39; H, 8.02; N, 12.38. Found: C, 58.33; H, 8.08; N, 12.30. 5-(ethoxycarbonyl)-4-(2-furyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (Table 2, entry 9)
O
O EtO Me N H NH O

M.P. 2032048C; 1H NMR (DMSO, 300 MHz): ^1.12 (t, 3H), 2.21 (s, 3H), 4.02 (q, 2H), 5.18 (d, 1H), 6.47.5 (m, 3H), 7.76 (s, 1H), 9.20 (s, 1H); FT-IR (KBr, cm1): 1644.0, 1706.1, 3240.2; MS (m/z): 250.29 (M); Anal. Calcd. for C12H14O4N2:C, 57.59; H, 5.64; N, 11.19. Found: C, 57.65; H, 5.70; N, 11.27. 5-(methoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (Table 2, entry 10)

O MeO Me N H NH O

M.P. 2072088C; 1H NMR (DMSO, 300 MHz): ^2.21 (s, 3H), 3.56 (s, 3H), 5.18 (d, 1H), 7.267.33 (m, 5H), 7.78 (s, 1H), 9.23 (s, 1H); FT-IR (KBr, cm1): 1642.0, 1701.1, 3231.8; MS (m/z): 246.21 (M); Anal. Calcd. for C13H14O3N2:C, 63.40; H, 5.73; N, 11.38. Found: C, 63.33; H, 5.79; N, 11.32. 5-(mehoxycarbonyl)-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (Table 2, entry 11)
OMe

O MeO Me N H NH O

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11

M.P. 2072088C; 1H NMR (DMSO, 300 MHz): ^2.24 (s, 3H), 3.53 (s, 3H), 3.72 (s, 3H), 5.09 (d, 1H), 6.88 (d, 2H), 7.14 (d, 2H), 7.69 (s, 1H), 9.19 (s, 1H); FT-IR (KBr, cm1): 1645, 1697, 3360; MS (m/z): 276.22 (M); Anal. Calcd. for C14H16O4N2:C, 60.87; H, 5.83; N, 10.14; Found: C, 60.85; H, 5.86; N, 10.16. 5-(methoxycarbonyl)-6-methyl-4-(4-nitrophenyl)-3,4-dihydropyrimidin-2(1H)-one (Table 2, entry 12)
NO2

O MeO Me N H NH O

M.P. 2352368C; 1H NMR (DMSO, 300 MHz): ^2.26 (s, 3H), 3.52 (s, 3H), 5.31 (d, 1H), 7.538.19 (m, 4H), 7.89 (s, 1H), 9.31 (s, 1H); FT-IR (KBr, cm1): 1692.8, 1712.6, 3232.4; MS (m/z): 291.21 (M); Anal. Calcd. for C13H13O5N3:C, 53.61; H, 4.50; N, 14.43. Found: C, 53.56; H, 4.53; N, 14.37. 5-(ethoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-thione (Table 2, entry 13)

O EtO Me N H NH S

M.P. 2072098C; 1H NMR (DMSO, 300 MHz): ^1.09 (t, 3H), 2.27 (s, 3H), 3.99 (q, 2H), 5.15 (d, 1H), 7.207.35 (m, 5H), 9.63 (s, 1H), 10.29 (s, 1H); FT-IR (KBr, cm1): 1578.3, 1672.7, 3181.2, 3339.8; MS (m/z): 276.31 (M); Anal. Calcd. For C14H16O2N2S:C, 60.85; H, 5.84; N, 10.14. Found: C, 60.78; H, 5.90; N, 10.08. 5-(ethoxycarbonyl)-6-methyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-thione (Table 2, entry 14)
OMe

O EtO Me N H NH S

M.P. 1501518C; 1H NMR (DMSO, 300 MHz): ^1.09 (t, 3H), 2.26 (s, 3H), 3.72 (s, 3H), 3.99 (q, 2H), 5.11 (s, 1H), 6.887.16 (m, 4H), 9.49 (s, 1H), 10.21 (s, 1H); FT-IR (KBr, cm1): 1561.4, 1599.0, 1651.2, 3250.8; MS (m/z): 306.32 (M); Anal. Calcd. For C15H18O3N2S:C, 58.80; H, 5.92; N, 9.14.Found: C, 58.74; H, 5.97; N, 9.19.

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5-(ethoxycarbonyl)-6-methyl-4-(4-Chlorophenyl)-3,4-dihydropyrimidin-2(1H)-Thione (Table 2, entry 15)

Cl

O EtO Me N H NH S

M.P. 1831858C; 1H NMR (CDCl3, 300 MHz): ^1.21 (t, 3H), 2.38 (s, 3H), 4.12 (q, 2H), 5.40 (s, 1H), 7.15 (s, 1H), 7.27 (d, 2H), 7.33 (d, 2H), 7.68 (s, 1H); FT-IR (KBr, cm1): 3329, 3174, 3103, 2983, 2935, 2360, 1722, 1573, 1465, 1371, 1282, 1203, 1093, 806, 746; MS (m/z): 310.66 (M); Anal. Calcd. For C14H15O2N2SCl:C, 54.10, H, 4.86; N, 9.01; Found: C, 54.07, H, 4.88, N, 9.03. General Procedure for the formation of 1,5-benzodiazepines In a 50 ml round-bottom flask, o-phenylenediamines (1 mmol) and ketones (2.2 mmol) were stirred in presence of Sn(HPO4)2.H2O nanodisks (10 mol%) under solvent-free condition at the room temperature. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added, catalyst was filtered off, and the products were purified by column chromatography on silica gel (60120 mesh) using ethyl acetate/hexane mixture as eluent to afford pure 1,5-benzodiazepines. Spectral data of the 1,5-benzodiazepines obtained by the condensation of ketone and 1,2-diamines 2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepine (Table 4, entry 1)
H N

M.P. 1361378C;1H NMR (CDCl3, 300 MHz): ^1.35 (s, 6H), 2.21 (s, 2H), 2.35 (s, 3H), 3.45 (s, 1H), 6.627.31 (m, 4H); FTIR (KBr, cm1): 3340.4, 1650.8; MS (m/z): 188.21 (M); Anal. Calcd. For C12H16N2:C, 76.55; H, 8.57; N, 14.88. Found: C, 76.49; H, 8.51; N, 14.80. 2,2,4-triethyl-3-methyl-2,3-dihydro-1H-1,5-benzodiazepine (Table 4, entry 2)
H N

M.P. 1431448C; 1H NMR (CDCl3, 300 MHz): ^0.751.05 (m, 10H), 1.201.40 (m, 4H), 1.481.64 (m, 2H), 2.402.59 (m, 2H), 2.87 (q, 1H), 3.73 (s, 1H), 6.55 (d, 1H), 6.64 (t, 1H), 6.90 (t, 1H), 7.36 (d, 1H); FT-IR (KBr, cm1): 3321.0, 1638.2; MS (m/ z): 244.29 (M); Anal. Calcd. For C16H24N2:C, 78.64; H, 9.90; N, 11.46. Found: C, 78.54; H, 9.80; N, 11.31. 2,4-diethyl-2-methyl-2,3-dihydro-1H-1,5-benzodiazepine (Table 4, entry 3)

Green Chemistry Letters and Reviews

H N

13

M.P. 1371388C; 1H NMR (CDCl3, 300 MHz): ^0.97 (t, 3H), 1.26 (t, 3H), 1.72 (q, 2H), 2.15 (m, 2H), 2.34 (s, 3H), 2.69 (q, 2H), 3.45 (s, 1H), 6.657.33 (m, 4H); FT-IR (KBr, cm 1): 3332.0, 1638.5; MS (m/z): 216.27 (M); Anal. Calcd. For C14H20N2:C, 77.73; H, 9.32; N, 12.95. Found: C, 77.65; H, 9.24; N, 12.83. 2-methyl-2,4-diphenyl-2,3-dihydro-1H-1,5-benzodiazepine (Table 4, entry 4)
Ph H N

N Ph

M.P. 1501518C; 1H NMR (CDCl3, 300 MHz): ^1.80 (s, 3H), 2.95 (d, 1H), 3.16 (d, 1H), 3.44 (s, 1H), 6.537.02 (m, 3H), 7.167.34 (m, 7H), 7.557.65 (m, 4H); FT-IR (KBr, cm1): 3330.9, 1635.2; MS (m/z): 312.48 (M); Anal. Calcd. For C22H20N2:C, 84.58; H, 6.45; N, 8.97. Found: C, 84.51; H, 6.38; N, 8.91. 2-methyl-2,4-diisobutyl-2,3-dihydro-1H-1,5-benzodiazepine (Table 4, entry 5)

H N

M.P. 1181208C; 1H NMR (CDCl3, 300 MHz): ^0.951.05 (m, 12H), 1.33 (s, 3H), 1.491.52 (m, 2H), 1.651.75 (m, 1H), 2.052.25 (m, 3H), 2.24 (d, 2H), 6.606.65 (m, 1H), 6.856.95 (m, 2H), 7.057.15 (m, 1H); FT-IR (KBr, cm1): 3330.7, 1637.5; MS (m/z): 272.32 (M); Anal. Calcd. For C18H28N2:C, 79.36; H, 10.36; N, 10.28. Found: C, 79.27; H, 10.23; N, 10.19. 10-spirocyclohexane-2,3,4,10,11,11a-hexahydro-1H-dibenzo[b,e][1,4]diazepine (Table 4, entry 6)

H N N

M.P. 1361378C; 1H NMR (CDCl3, 300 MHz): ^1.231.86 (m, 16H), 2.302.70 (m, 3H), 4.47 (s, 1H), 6.697.70 (m, 4H); FTIR (KBr, cm  1): 3290.9, 1640.2; MS (m/z): 268.24 (M); Anal. Calcd. for C18H24N2:C, 80.55; H, 9.01; N, 10.44. Found: C, 80.46; H, 9.10; N, 10.35.