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Ammonium acetate catalyzed an efficient one-pot three component synthesis of pyrano[3,2-c]chromene derivatives
⁎Corresponding author. Tel.: +91 8702462660. gvpc2000@gmail.com (G.V.P. Chandramouli)
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Received: ,
Accepted: ,
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.
Peer review under responsibility of King Saud University.
Abstract
An efficient and simple procedure has been described using ammonium acetate as catalyst for the synthesis of 3,4-dihydropyrano[3,2-c]chromene derivatives by one-pot three component condensation of 4-hydroxycoumarin, various aryl/heteryl aldehydes and malononitrile. The attractive features of the present methodology are excellent yields, short reaction times and environmentally benign milder reaction conditions.
Keywords
Multicomponent reaction
4-Hydroxycoumarin
3,4-Dihydropyrano[3,2-c]chromene
Ammonium acetate
Single-crystal X-ray diffraction
1 Introduction
One-pot multi-component reaction strategies offer significant advantages over conventional linear-type syntheses by virtue of their convergence, productivity, facile execution and high yield (Weber, 2002; Domling, 2002). Because of these advantages, developing new reaction (MCR) with environmentally benign methods has been recognized as one of the most important topics of green chemistry (Tan et al., 2010; Yang et al., 2010). The development of multi-component reactions designed to produce elaborate biologically active compounds has become an important area of research in organic, combinatorial, and medicinal chemistry (Domling and Ugi, 2000; Orru and de Greef, 2003).
3,4-Dihydropyrano[3,2-c]chromenes and their derivatives have a wide range of applications in various fields of chemistry, biology and pharmacology. Some of these compounds exhibit spasmolytic, diuretic, anticoagulant, anticancer, and antianaphylactic activities (Green et al., 1995; Foye, 1991; Bonsignore et al., 1993). In addition, they can be used as cognitive enhancers for the treatment of neurodegenerative diseases, including Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, Huntington’s disease, AIDS associated dementia, Down’s syndrome, and for the treatment of schizophrenia and myoclonus (Konkoy et al., 2000). In the literature, fewer methods have been reported for the synthesis of 3,4-dihydropyrano[3,2-c]chromenes in the presence of a variety of catalysts such as K2CO3 under microwave irradiation (Kidwai and Saxena, 2006), diammonium hydrogen phosphate, (S)-proline (Abdolmohammadi and Balalaie, 2007), H6P2W18O6218H2O (Heravi et al., 2008), TBAB (Khurana and Kumar, 2009) and DBU (Khurana et al., 2010). 2-Amino-4-aryl-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitriles have already been prepared in the presence of organic bases such as piperidine or pyridine in a large volume of organic solvents such as absolute ethanol under thermal conditions (Shaker, 1996). However, some of these reported methods suffer from drawbacks such as harsh reaction conditions, unsatisfactory yields, prolonged reaction times, and cumbersome product isolation procedures. Hence, the development of new methods with the objective of improved yields using green chemistry for the synthesis of above said molecules is a welcome goal because of the wide spectrum of biological activities these molecules possess. As a part of our continuing research in developing environmental friendly methodologies (Kanakaraju et al., 2012), we describe herein a green, efficient, and rapid procedure for the synthesis of 3,4-dihydropyrano[3,2-c]chromene derivatives by a one-pot three component condensation reaction of 4-hydroxycoumarin, aldehydes, and malononitrile using ammonium acetate as the catalyst in excellent yields (Scheme 2).![Model reaction for the synthesis of 2-amino-4,5-dihydro-5-oxo-4-phenylpyrano[3,2-c]chromene-3-carbonitrile 4a catalyzed by NH4OAc.](/content/184/2017/10/2_suppl/img/10.1016_j.arabjc.2013.10.014-fig1.png)
Model reaction for the synthesis of 2-amino-4,5-dihydro-5-oxo-4-phenylpyrano[3,2-c]chromene-3-carbonitrile 4a catalyzed by NH4OAc.
![Synthesis of 3,4-dihydropyrano[3,2-c]chromenes catalyzed by NH4OAc.](/content/184/2017/10/2_suppl/img/10.1016_j.arabjc.2013.10.014-fig2.png)
Synthesis of 3,4-dihydropyrano[3,2-c]chromenes catalyzed by NH4OAc.
2 Experimental
Melting points were recorded in open capillary and were uncorrected. Thin Layer Chromatography (TLC) was carried out using aluminum sheets pre-coated with silica gel 60F254 purchased from Merck. IR spectra (KBr) were obtained using a Bruker WM-4(X) spectrometer (577 model). 1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded on a Bruker WM-400 spectrometer in DMSO-d6 with TMS as an internal standard. Mass spectra (ESI) were carried out on a JEOL SX-102 spectrometer. CHN analysis was done by Carlo Erba EA 1108 automatic elemental analyzer. The compound 4a was crystallized from N,N-dimethylformamide and the crystal data were collected on a Bruker Kappa APEX-II CCD DUO diffractometer. The chemicals and solvents used were of commercial grade and were used without further purification unless otherwise stated.
2.1 General procedure for the synthesis of 3,4-dihydropyrano[3,2-c]chromenes (4a–t)
A mixture of aldehyde (1 mmol), malononitrile (1 mmol), 4-hydroxycoumarin (1 mmol) and ammonium acetate (15 mol%, 0.15 mmol, 11.7 mg) in ethanol (5 mL) was refluxed for an appropriate time as mentioned in Table 4. Upon completion of the reaction, monitored by TLC, the reaction mixture was allowed to cool to room temperature. The solid seperated was filtered off, washed with ethanol and purified by recrystallization from aqueous ethanol to afford the products 4a–t. aReaction conditions: aldehyde 1a (1 mmol), malononitrile 2 (1 mmol), 4-hydroxycoumarin 3 (1 mmol), NH4OAc (15 mol%), and EtOH (5 mL). bIsolated yields after purification.
Entry
R
Product
Time (min)
Yield (%)
Mp (°C) [obs]
Mp (°C) [lit]
1
4a
3
94
258–260
256–258 Khurana et al. (2010)
2
4b
4
92
263–265
260–262 Khurana et al. (2010)
3
4c
6
90
260–262
262–263 Khurana et al. (2010)
4
4d
4
94
253–255
252–254 Khurana et al. (2010)
5
4e
8
90
252–254
253–255 Khurana et al. (2010)
6
4f
10
89
246–248
248–250 Khurana et al. (2010)
7
4g
5
93
258–260
256–258 Khurana et al. (2010)
8
4h
12
88
265–267
266–267 Khurana et al. (2010)
9
4i
10
89
222–224
224–225 Khurana et al. (2010)
10
4j
8
85
264–266
266–268 Wang et al. (2004)
11
4k
10
86
261–263
262–264 Abdolmohammadi and Balalaie (2007)
12
4l
20
84
252–254
252–253 Abd-El-Aziz et al. (2004)
13
4m
10
88
242–245
–
14
4n
20
84
227–230
–
15
4o
10
90
250–252
–
16
4p
7
91
198–201
–
17
4q
10
89
218–221
–
18
4r
12
91
260–263
–
19
4s
8
92
249–251
–
20
4t
10
90
207–210
–
Some of the synthesized compounds 4a–l are reportedly known, and were identified by comparison of spectral and physical data with the literature (Khurana et al., 2010; Wang et al., 2004; Abdolmohammadi and Balalaie, 2007; Abd-El-Aziz et al., 2004). Other products 4m–t, which are new, were characterized by their mp, IR, 1H NMR, 13C NMR, and mass and elemental analysis.
2.1.1 Selected spectroscopic data
2.1.1.1 2-Amino-4,5-dihydro-5-oxo-4-phenylpyrano[3,2-c]chromene-3-carbonitrile (4a)
See reference (Khurana et al., 2010).
2.1.1.2 2-Amino-4,5-dihydro-4-(2-nitrophenyl)-5-oxopyrano[3,2-c]chromene-3-carbonitrile (4m)
IR (KBr, cm−1): 3377, 3274, 2196, 1708, 1676, 1604, 1382, 1163. 1H NMR (DMSO-d6, 400 MHz): δ 4.61 (s, 1H, H-4), 7.10 (d, 1H, H-7), 7.28–7.32 (m, 2H, H-4′,6′), 7.45–7.48 (m, 3H, H-8 + NH2), 7.51 (t, 1H, H-9), 7.73 (t, 1H, H-5′), 7.92 (d, 1H, H-10), 8.10 (d, 1H, H-3′) ppm. 13C NMR (DMSO-d6, 100 MHz): δ 35.87 (C-4), 56.82 (C-3), 103.14 (C-4a), 113.38, 116.07, 117.15 (CN), 119.53, 122.96, 125.12, 129.74, 130.37, 130.84, 133.68, 152.61 (C-2′), 154.42 (C-7a), 158.71 (C-2), 159.91 (C-10b), 160.08 (C⚌O) ppm. ESI-MS (m/z): 362 (M+1)+. Anal. Calcd for C19H11N3O5: C, 63.16; H, 3.07; N, 11.63. Found: C, 63.24; H, 3.13; N, 11.57.
2.1.1.3 2-Amino-4,5-dihydro-4-(3,4-dimethoxyphenyl)-5-oxopyrano[3,2-c]chromene-3-carbonitrile (4n)
IR (KBr, cm−1): 3403, 3326, 2196, 1710, 1672, 1609, 1378, 1174. 1H NMR (DMSO-d6, 400 MHz): δ 3.82 (s, 6H, 2 × OCH3), 4.53 (s, 1H, H-4), 6.76 (s, 1H, H-2′), 6.88 (d, 2H, H-5′,6′), 7.32–7.44 (m, 4H, H-7,8 + NH2), 7.64 (t, 1H, H-9), 7.88 (d, 1H, H-10) ppm. 13C NMR (DMSO-d6, 100 MHz): δ 36.53 (C-4), 55.52 (OCH3), 55.58 (OCH3), 58.27 (C-3), 104.08 (C-4a), 111.63, 111.94, 112.87, 116.58 (CN), 119.38, 119.97, 122.42, 124.53, 132.74, 135.82, 148.03, 148.68, 152.01 (C-7a), 153.10 (C-2), 157.91 (C-10b), 159.46 (C⚌O) ppm. ESI-MS (m/z): 377 (M+1)+. Anal. Calcd for C21H16N2O5: C, 67.02; H, 4.28; N, 7.44. Found: C, 67.10; H, 4.22; N, 7.49.
2.1.1.4 2-Amino-4,5-dihydro-4-(naphthalen-1-yl)-5-oxopyrano[3,2-c]chromene-3-carbonitrile (4o)
IR (KBr, cm−1): 3380, 3271, 2198, 1710, 1663, 1602, 1378, 1178. 1H NMR (DMSO-d6, 400 MHz): δ 4.52 (s, 1H, H-4), 7.08–7.14 (m, 3H, H-7,8,2′), 7.21–7.26 (m, 4H, H-3′,7′ + NH2), 7.41 (d, 1H, H-4′), 7.52–7.57 (m, 3H, H-9,5′,6′), 7.70 (d, 1H, H-8′), 7.88 (d, 1H, H-10) ppm. 13C NMR (DMSO-d6, 100 MHz): δ 36.82 (C-4), 58.11 (C-3), 106.35 (C-4a), 117.21 (CN), 117.93, 121.67, 123.61, 124.18, 124.87, 125.02, 125.75, 126.10, 126.83, 127.28, 128.92, 133.43, 134.15, 138.29, 145.24, 152.27 (C-7a), 157.22 (C-2), 157.87 (C-10b), 159.38 (C⚌O) ppm. ESI-MS (m/z): 367 (M+1)+. Anal. Calcd for C23H14N2O3: C, 75.40; H, 3.85; N, 7.65. Found: C, 75.47; H, 3.81; N, 7.71.
2.1.1.5 2-Amino-4,5-dihydro-4-(2-methoxynaphthalen-6-yl)-5-oxopyrano[3,2-c]chromene-3-carbonitrile (4p)
IR (KBr, cm−1): 3370, 3278, 2196, 1703, 1653, 1600, 1376, 1168. 1H NMR (DMSO-d6, 400 MHz): δ 3.85 (s, 3H, OCH3), 4.58 (s, 1H, H-4), 7.14 (dd, 1H, H-7), 7.28 (d, 1H, H-6′), 7.35 (dd, 1H, H-2′), 7.43–7.51 (m, 4H, H-8,4′ + NH2), 7.70–7.77 (m, 3H, H-9,3′,8′), 7.82 (d, 1H, H-7′), 7.93 (d, 1H, H-10) ppm. 13C NMR (DMSO-d6, 100 MHz): δ 37.02 (C-4), 55.13 (OCH3), 58.07 (C-3), 103.90 (C-4a), 105.73, 113.01, 116.53 (CN), 118.67, 119.21, 122.48, 124.61, 126.02, 126.25, 127.08, 128.22, 129.23, 132.85, 133.47, 138.29, 152.14 (C-7a), 153.35 (C-2), 157.22 (C-5′), 157.87 (C-10b), 159.53 (C⚌O) ppm. ESI-MS (m/z): 397 (M+1)+. Anal. Calcd for C24H16N2O4: C, 72.72; H, 4.07; N, 7.07. Found: C, 72.77; H, 4.11; N, 7.02.
2.1.1.6 2-Amino-4,5-dihydro-4-(1H-indol-3-yl)-5-oxopyrano[3,2-c]chromene-3-carbonitrile (4q)
IR (KBr, cm−1): 3435, 3392, 3298, 2197, 1703, 1662, 1602, 1373, 1182. 1H NMR (DMSO-d6, 400 MHz): δ 4.74 (s, 1H, H-4), 6.94 (dd, 1H, H-2′), 7.05 (d, 1H, H-7), 7.29–7.36 (m, 5H, H-4′,5′ + NH2), 7.43 (d, 1H, H-7′), 7.50 (t, 1H, H-8), 7.69 (t, 1H, H-9), 7.94 (d, 1H, H-10), 11.01 (s, 1H, NH) ppm. 13C NMR (DMSO-d6, 100 MHz): δ 38.05 (C-4), 69.23 (C-3), 110.95 (C-4a), 113.01, 115.87, 115.92 (CN), 119.00, 122.53, 123.91, 126.68, 128.41, 133.23, 136.14, 152.48 (C-7a), 154.52 (C-2), 158.73 (C-10b), 159.92 (C⚌O) ppm. ESI-MS (m/z): 356 (M+1)+. Anal. Calcd for C21H13N3O3: C, 70.98; H, 3.69; N, 11.83. Found: C, 70.91; H, 3.62; N, 11.90.
2.1.1.7 2-Amino-4-(4-chloro-4a,8a-dihydro-2-oxo-2H-chromen-3-yl)-4,5-dihydro-5-oxopyrano[3,2-c]chromene-3-carbonitrile (4r)
IR (KBr, cm−1): 3395, 3296, 2194, 1715, 1710, 1667, 1604, 1377, 1185. 1H NMR (DMSO-d6, 400 MHz): δ 4.63 (s, 1H, H-4), 7.56–7.65 (m, 5H, H-7,8,6′ + NH2), 7.84–7.88 (m, 2H, H-9,5′), 8.43 (d, 2H, H-10,4′), 8.99 (d, 1H, H-7′) ppm. 13C NMR (DMSO-d6, 100 MHz): δ 36.02 (C-4), 57.41 (C-3), 100.72 (C-4a), 112.34, 116.86 (CN), 120.21, 123.44, 124.70, 125.28, 128.52, 134.24, 145.03 (C-8′a), 152.20 (C-7a,4′a), 155.72 (C-2), 160.03 (C-10b), 162.05 (2 × C⚌O) ppm. ESI-MS (m/z): 419 (M+1)+. Anal. Calcd for C22H11ClN2O5: C, 63.10; H, 2.65; N, 6.69. Found: C, 63.17; H, 2.70; N, 6.61.
2.1.1.8 2-Amino-4-(2-chloroquinolin-3-yl)-4,5-dihydro-5-oxopyrano[3,2-c]chromene-3-carbonitrile (4s)
IR (KBr, cm−1): 3397, 3293, 2198, 1710, 1663, 1602, 1370, 1181. 1H NMR (DMSO-d6, 400 MHz): δ 5.14 (s, 1H, H-4), 7.48–7.63 (m, 4H, H-7,8 + NH2), 7.65–7.73 (m, 1H, H-4′), 7.74–7.79 (m, 2H, H-3′,5′), 7.81–8.02 (m, 3H, H-9,10,6′), 8.53 (s, 1H, H-2′) ppm. 13C NMR (DMSO-d6, 100 MHz): δ 34.58 (C-4), 56.06 (C-3), 102.33 (C-4a), 112.89, 116.61 (CN), 118.67, 122.54, 124.69, 127.29, 127.39, 127.83, 130.79, 133.06, 139.43, 146.07, 149.22 (C-7a), 152.26 (C-Cl), 154.22 (C-2), 158.10 (C-10b), 159.53 (C⚌O) ppm. ESI-MS (m/z): 402 (M+1)+. Anal. Calcd for C22H12ClN3O3: C, 65.76; H, 3.01; N, 10.46. Found: C, 65.71; H, 3.08; N, 10.39.
2.1.1.9 2-Amino-4-(2-butyl-5-chloro-1H-imidazol-4-yl)-4,5-dihydro-5-oxopyrano[3,2-c]chromene-3-carbonitrile (4t)
IR (KBr, cm−1): 3442, 3397, 3287, 2197, 1708, 1666, 1600, 1379, 1187. 1H NMR (DMSO-d6, 400 MHz): δ 0.85 (t, 3H, CH3), 1.23–1.31 (sext, 2H, CH2), 1.50–1.58 (pent, 2H, CH2), 2.46–2.50 (m, 2H, CH2), 4.57 (s, 1H, H-4), 7.41–7.50 (m, 2H, H-7,8), 7.52 (s, 2H, NH2), 7.72 (t, 1H, H-9), 7.89 (d, 1H, H-10), 12.04 (s, 1H, NH) ppm. 13C NMR (DMSO-d6, 100 MHz): δ 15.27 (C-4″), 23.46 (C-3″), 32.03 (C-2″), 33.12 (C-1″), 36.68 (C-4), 56.11 (C-3), 105.32 (C-4a), 117.12 (CN), 118.07, 122.53, 125.62, 126.91, 128.75, 145.96, 149.31, 151.38 (C-4′), 152.17 (C-7a), 154.31 (C-2), 158.47 (C-10b), 159.48 (C⚌O) ppm. ESI-MS (m/z): 397 (M+1)+. Anal. Calcd for C20H17ClN4O3: C, 60.53; H, 4.32; N, 14.12. Found: C, 60.57; H, 4.37; N, 14.08.
3 Results and discussion
Initially, we performed a model reaction using benzaldehyde (1 mmol) 1a, malononitrile (1 mmol) 2, 4-hydroxycoumarin 3 (1 mmol) and ammonium actate (NH4OAc) 4 (1 mmol) in EtOH (5 mL) at reflux temperature (Scheme 1). We thought that, ammonium acetate is also participated in the above said reaction to form the product 5a, but single crystal X-ray diffraction data (Fig. 1) revealed that ammonium acetate was not involved in the reaction and the product could be 4a. From this observation it is evident that ammonium acetate was used as a catalyst, but not as a reactant in the above model reaction.
ORTEP representation of compound 4a·DMF solvate. Thermal ellipsoids are drawn at 50% probability level.
Next, we investigated the effect of catalyst amount on the yield and rate of the reaction using different amounts of ammonium acetate. We found that an increase in the amount of ammonium acetate from 5 to 15 mol% not only decreased the reaction time from 30 to 3 min but also increased product yield from 86% to 94% (Table 1, entries 1–3). This showed that the catalyst concentration plays a major role in the optimization of the product yield. It seems noteworthy to mention that only 10% of the desired product was formed in the absence of the catalyst, and when the amount of ammonium acetate was further increased from 15% to 30% no remarkable increment in the yield was observed (Table 1, entries 3–5). Therefore 15 mol% of ammonium acetate could be used as an efficient catalyst for the synthesis of 3,4-dihydropyrano[3,2-c]chromene derivatives (Table1, entry 3).
Entry
Catalyst
Mol%
Time (min)
Yieldb (%)
1
NH4OAc
5
30
86
2
NH4OAc
10
10
92
3
NH4OAc
15
3
94
4
NH4OAc
20
3
92
5
NH4OAc
30
3
94
6
No Catalyst
–
720
10
Although we have not yet established the mechanism, a possible explanation is given in Scheme 3. We believe that, ammonium acetate catalyses the formation of iminium ion in a reaction with the aldehyde. The higher reactivity of the iminium ion compared to the carbonyl species is utilized to facilitate Knoevenagel condensation between aldehyde and malononitrile, via an intermediate followed by the elimination of ammonium ion to produce an alkene. Later, 4-hydroxycoumarin adds to alkene, followed by rearrangement and proton transfer to give title product.![A plausible mechanism for the synthesis of 3,4-dihydropyrano[3,2-c]chromenes catalyzed by NH4OAc.](/content/184/2017/10/2_suppl/img/10.1016_j.arabjc.2013.10.014-fig4.png)
A plausible mechanism for the synthesis of 3,4-dihydropyrano[3,2-c]chromenes catalyzed by NH4OAc.
Various solvents were also screened to test their efficiency in the reaction at different reflux temperatures, and the results are summarized in Table 2. As shown in Table 2, the reaction using ethanol as the solvent gave the target compound in high yields and in a short reaction time (Table 2, entry 8). Therefore, the best reaction conditions were obtained by using 15 mol% of ammonium acetate as the catalyst in EtOH at reflux temperature. To prove ammonium acetate was an efficient catalyst, we performed the same model reaction using different catalysts in ethanol and the results are presented in Table 3. As can be seen from Table 3, lower yields of 4a were obtained when p-toluenesulfonic acid (PTSA), NH2SO3H, SiO2–NaHSO3 and triethylamine (TEA) were employed in ethanol after reacting for 2 h at reflux temperature (Table 3, entries 1–4). When the reaction was performed in the presence of ammonium acetate, to our delight, it proceeded mildly and rapidly to give the desired product in 94% yield. Therefore ammonium acetate was found to be the most effective catalyst in terms of reaction time and yields (Table 3, entry 5).
Entry
Solvent
Temp (°C)
Time (min)
Yieldb (%)
1
CH2Cl2
Reflux
120
Trace
2
CH3CN
Reflux
90
45
3
THF
Reflux
90
30
4
AcOH
Reflux
30
72
5
DMF
100
30
75
6
MeOH
Reflux
20
88
7
EtOH
RT
60
Trace
8
EtOH
Reflux
3
94
Entry
Catalyst
Mol (%)
Time (min)
Yield of 4ab (%)
1
pTSA
20
90
38
2
NH2SO3H
30
100
45
3
SiO2-NaHSO3
30
120
48
4
TEA
20
120
52
5
NH4OAc
15
3
94
After optimizing the reaction conditions, we next explore the scope and efficiency of this approach using various aromatic and heteroaromatic aldehydes and the results are summarized in Table 4. As shown in Table 4, aromatic aldehydes carrying either electron-donating or electron-withdrawing substituents have reacted efficiently giving excellent yields (Table 4, entries 1–16). Hence, the effect of the nature of the substituents on the aromatic ring showed no obvious effect on this conversion. It is noteworthy to mention that this method also worked well with heterocyclic aldehydes giving excellent yields (Table 4, entries 17–20).
Except for compounds 4m–t, all products are known compounds. The spectroscopic and physical data for all known compounds were found to be identical to those described in the literature.
3.1 Single crystal X-ray diffraction
The single-crystal X-ray diffraction data of the crystal were collected on a Bruker Kappa APEX-II CCD DUO diffractometer at 296(2) K using graphite-monochromated Mo Kα radiation (λ = 0.71073 Å). No absorption correction was applied. The lattice parameters were determined from least-squares analysis, and reflection data were integrated using the program (SHELXTL, 2000). The crystal structures were solved by direct methods using SHELXS-97 and refined by full-matrix least-squares refinement on F2 with anisotropic displacement parameters for non-H atoms using SHELXL-97 (Sheldrick, 1997). N–H and O–H hydrogens were refined from difference Fourier maps. The positions of all aromatic and aliphatic C–H hydrogen atoms were calculated geometrically, and a riding model was used in the refinement, with C–H distances in the range of 0.93–0.98 Å and Uiso(H) = 1.5 Ueq(C). The software used to prepare the material for publication was Mercury 2.3 (Build RC4), ORTEP-3 and X-Seed (Macrae et al., 2008; Farrugia, 1997; Barbour, 2001). Table 5 gives the pertinent crystallographic data, and Table 6 gives hydrogen bond parameters.
4a·DMF
Empirical formula
C19H12N2O3·C3H7NO
Formula weight
389.40
Crystal system
Triclinic
Space group
P-1
T/K
293 (2)
a/Å
5.9170 (15)
b/Å
11.784 (2)
c/Å
15.019 (5)
α/°
71.78 (2)
β/°
82.99 (2)
γ/°
81.768 (19)
Z
2
V/Å3
981.1 (4)
Dcalc/g/cm3
1.315
F(0 0 0)
408
μ/mm−1
0.092
θ/°
2.87–26.37
Index ranges
−7 ⩽ h ⩽ 7
−14 ⩽ k ⩽ 11
−18 ⩽ l ⩽ 18
N-total
6831
N-independent
4017
N-observed
1467
Parameters
266
R1 (I > 2σ(I))
0.0849
wR2 (all data)
0.1748
GOF
1.017
Compound
D–H···Aa
D···A (Å)
H···A (Å)
D–H···A (°)
Symmetry code
4a
Intra N(1)–H(2A)···N(2)
3.570 (6)
2.94
121
–
N(1)–H(2A)···N(2)
2.995 (6)
2.18
136
−x,−y,1−z
N(1)–H(2B)···O(1)
3.096 (13)
2.35
130
−1 + x,y,z
C(2)–H(2)···O(3)
3.364 (6)
2.28
179
−1 + x,y,z
C(7)–H(7)···N(1)
3.503 (6)
2.61
140
1 + x,y,z
C(7)–H(7)···N(2)
3.653 (6)
2.80
136
1−x,−y,1−z
C(19)–H(19)···O(2)
3.648 (6)
2.63
157
2−x,1−y,−z
C(19)–H(19)···O(3)
3.646 (6)
2.68
149
2−x,1−y,−z
C(20)–H(20B)···N(1)
3.549 (9)
3.01
111
1−x,1−y,1−z
C(20)–H(20C)···O(1)
3.570 (14)
2.73
134
1−x,1−y,1−z
3.2 Crystal structure analysis
With regard to crystal structure of 4a, the compound forms DMF solvate in the crystal. 4a·DMF solvate crystallizes in the centrosymmetric triclinic P-1 space group with one molecule of 4a and one molecule of DMF in the asymmetric unit (Z′ = 2) (Fig. 1). The molecules of compound 4a form supramolecular homodimer synthon layers in the crystal structure and the DMF molecules are interacting with these dimers. The two molecules of 4a forms suprmolecular homodimer synthons with hydrogen bond donor N–H group of amine and hydrogen bond acceptor C≡N group forming N–H···N hydrogen bonding. Each dimer synthon interacts with the two DMF molecules via N–H···O hydrogen bonds (Fig. 2). These zero dimensional discrete dimer synthons are propagated by interacting with another homodimer synthons via weak C–H···O homodimer synthons and forms one dimensional (1D) tape like structure (Fig. 3). These 1D tapes are forming layers by C–H···O and weak C–H···π interactions.
Supramolecular homodimer synthons are formed by two 4a molecules via N–H···N hydrogen bonds. The two DMF molecules are connected to homodimer synthon with N–H···O hydrogen bonds.
1D tape like structure formed by the supramolecular homodimer synthons via N–H···N and C–H···O hydrogen bonds.
4 Conclusion
In summary, we have demonstrated an elegant protocol for the synthesis of 3,4-dihydropyrano[3,2-c]chromene derivatives by using ammonium acetate as the catalyst. This protocol offers several advantages including mild reaction conditions, excellent yields, short reaction time, inexpensive catalyst, wide scope of substrates and operational simplicity, simple work-up, and purification of products by non-chromatographic methods.
Acknowledgements
We are thankful to the Director, National institute of Technology, Warangal for providing facilities and financial support. We are also thankful to the University of Hyderabad for providing single crystal X-ray data collection.
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