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Open Access Full Text Article Research Paper
[DBN][HSO4]-Promoted facile and green synthesis of 2-Amino-4H-pyrans derivatives under microwave irradiation
Vishal U. Mane,a,b Dhananjay V. Maneb,c*
a Department of Chemistry, RNC Arts, JDB Commerce & NSC Science College, Nashik (MS) 422101, India
b Department of Chemistry, Shri Chhatrapati Shivaji College, Omerga, Dist. Osmanabad (MS), 413606, India
c Professor & Regional Director, Yashwantrao Chavan Maharashtra Open University, Nashik (MS), 422222, India
Article Info: _________________________________________ Article History: Received 07 Feb 2021 Review Completed 28 March 2021 Accepted 07 April 2021 Available online 18 April 2021 _________________________________________ *Address for Correspondence: Dhananjay V. Mane, Department of Chemistry, Shri Chhatrapati Shivaji College, Omerga, Dist. Osmanabad (MS), 413606, India |
Abstract _________________________________________________________________________________________________________ The [DBN][HSO4] -promoted Knoevenagel condensation followed by cyclization protocol has been developed for the first time by a successive reaction of aldehydes, dimedone and malononitrile to afford 2-Amino-4H-pyrans derivatives in high to excellent yields at room temperature. The synergic couple of microwave and ionic liquid provided the capability to allow a variability of functional groups, short reaction times, easy workup, high yields, recyclability of the catalyst, and solvent-free conditions, thus providing economic and environmental advantages. Keywords: [DBN][HSO4], Environmentally benign, 2-Amino-4H-pyrans, Knoevenagel condensation, Microwave irradiation |
Cite this article as: Mane VU, Mane DV, [DBN][HSO4]-Promoted facile and green synthesis of 2-Amino-4H-pyrans derivatives under microwave irradiation, Journal of Drug Delivery and Therapeutics. 2021; 11(2-s):89-97 DOI: http://dx.doi.org/10.22270/jddt.v11i2-s.4824 |
INTRODUCTION
2-Amino-4H-pyrans derivatives have been investigated for a wide range of pharmacologic indications such as potent bioactive compounds found in dyes, cosmetics, pigments
and also utilized in agrochemicals because of their biodegradable properties.1-3 Many of the natural product isolated resemble the structure of the poly functionalized 4H pyrans,4-5 represented several biological activities,6 such as antibacterial,7-11 anti-allergic,2 antitumor,12 calcium channel antagonists,13 anti-HIV,14 antitubercular,15 antimalarial16 and anticancer,17 The structures of representative compounds are shown in Fig. 1.
Figure 1: 2-Amino-4H-pyrans incorporated bioactive molecules.
Multicomponent reactions (MCRs) have received increasing attention due to their simplicity, efficiency, atom economy, short reaction times and the possibility for diversity-oriented synthesis.18 Moreover, the incorporation of solvent-free methods in MCRs makes the process cleaner, safer and easier to perform.19 Thus, the utilization of MCRs coupled with environmentally benign solvent-free condition is highly desirable. Owing to an extensive range of MCRs applications in different areas like the preparation of different structural scaffolds
and the detection of new drugs, these types of reactions have drawn considerable attention in organic synthesis and pharmaceutical chemistry.20 Besides, Ionic liquids (ILs) have taken the attention of the chemical community all over the globe as a green alternative option to traditional ecofriendly media for catalysis, synthesis, separation, and other several chemical tasks.21-26 ILs include numerous exclusive properties, such as extensive liquid range, nonvolatility, low toxicity, high thermal stability, noncombustible, excellent solubility, and recyclability.27 ILs act as “neoteric solvents” for a wide range of industrial and chemical processes. In recent times, ILs have been originating to be valuable as environmental friendly media for countless organic revolutions.28-29 Recently, DBN was widely used as catalysts in different research area. The combination of DBN with cation to give the formation of novel ionic liquids.30 The large number of functionalized ILs has been considered for diverse purposes.31
The use of microwave irradiation in combination with ILs, which has very high heat capacity, high polarity and no vapor pressure, and their high potentiality to absorb microwaves and convert them into heat energy, may accelerate the reaction very quickly. The synergy of microwave and ionic liquid in catalyst-free methodologies for the synthesis of heterocyclic compounds has attracted much interest because of the shorter reaction time, milder conditions, reduced energy consumption and higher product selectivity and yields.34
Thus, the extension of synthetic route for the construction of this molecule using an reusable, economical, nontoxic and mild catalyst is of massive importance from the
academic and industrial points of view. Even though various modes have been reported in the literature, these reactions can be accomplished under a variability of tentative conditions, and several improvements have been reported in recent years, such as hexadecyltrimethylammonium bromide,35 tetrabutylammonium bromide,36 Mg/La mixed oxide,37 (S)-proline,38 Tetramethylguanidine-[bmim][BF4]39 and MgO.40 Some of the new catalysts reported recently such as CeV/SiO2,41 BNFe3O4,42 PPh3,42 ZnFe2O4@ alginic acid,43 Chitosan‐CTAB,44 MCM-41@Schiff base-Co(OAc)2,45 Fe3O4@SiO2@TiO2,46 Fe3O4@xanthan gum,47 saccharose,48 and muskmelon fruit shell (WEMFSA).49 However, numerous of these testified methods become infected with several disadvantages such as strong acidic conditions, use of hazardous or costly reagents, long reaction times, low yields of products, and sophisticated treatment. Moreover, many of these schemes utilize organic solvents as the reaction medium. Hence, the further innovation toward contemporary reaction with easy isolation of product, reusability of catalyst, perhaps with minimal or no waste is highly attractive.
As per our investigation, the existential of this work is to begin a rapid and efficient synthetic protocol for obtaining 2-Amino-4H-pyrans derivatives under ecofriendly conditions. As an extension of emerging economic and efficient strategy to develop pharmaceutically and biologically significant molecules, herein, we reported synthesis of library of 2-Amino-4H-pyrans derivatives promoted by synergistic effect of ionic liquid and microwave irradiation without any added catalyst in good to excellent yields.
RESULTS AND DISCUSSION
Chemistry
To achieve optimized conditions protocol based on the reaction of benzaldehyde (1a) (1 mmol), dimedone (2) (1 mmol) and malononitrile (3) (1 mmol) as model reaction (Scheme 1), we checked temperatures and solvents, catalyst loading and the results of this study are summarized in Table 1.
Scheme 1: Model reaction
Firstly, the model reaction was performed using 20 mol% of catalyst under reflux condition in different solvents (Table 1). The model reaction carried out in MeOH and EtOH (Table 1, entry 1, and 2) was completed in 10 min with the yield of 64 and 59%, respectively. Whereas, in tert-BuOH (Table 1, entry 3), a better yield (71%) was obtained in 45 min. In H2O and THF, decreased yields (47 and 51%) of the product 3a were obtained (Table 1, entries 4-5). Conducting the reaction in Toluene, CH3CN and DMF (Table 1, entries 6-8), does not improve the yield of the product. However, when the model reaction was carried out under a solvent-free condition with 20 mol% [DBN][HSO4], a significant increase in the yield was observed (Table 1). Therefore it proved that the solvent-free condition is best suited for the transformation. Therefore, it can be thought that [DBN][HSO4] is green and a superior solvent and catalyst compared to the others shown in Table 1.
Table 1: Optimizations of the reaction conditions for the synthesis of 2-Amino-4H-pyrans derivatives 4aa
Entry |
Solvent |
Temp (°C) |
Yieldb (%) |
1 |
MeOH |
Reflux |
64 |
2 |
EtOH |
Reflux |
59 |
3 |
Tert-BuOH |
Reflux |
71 |
4 |
H2O |
Reflux |
47 |
5 |
THF |
Reflux |
51 |
6 |
Toluene |
Reflux |
42 |
7 |
DMF |
Reflux |
47 |
8 |
CH3CN |
Reflux |
51 |
9 |
Solvent-free |
80 |
95 |
aReaction conditions: aldehyde 1a (1 mmol), dimedone 2 (1 mmol), malononitrile (3) (1 mmol) and [DBN][HSO4] (20 mol%) stirred at under microwave irradiation (MW = 280 W). bIsolated yields. Bold values are for highlighting the good result.
|
In the next step we examine the efficiency of ionic liquid [DBN][HSO4] for the synthesis of 2-Amino-4H-pyrans derivatives. When change in concentration of [DBN][HSO4] on model reaction suggest that much more effect on yield of final product. The catalyst loading study suggest that 20 mol% of [DBN][HSO4] catalyst are best for the synthesis of final product in 95% yields (Table 2).
Table 2: Effect of catalyst concentrationa
Entry |
Catalyst (mol %) |
Time (min) |
Yieldb (%) |
1 |
5 |
20 |
65 |
2 |
10 |
15 |
74 |
3 |
15 |
12 |
86 |
4 |
20 |
7 |
95 |
5 |
25 |
7 |
95 |
aReaction conditions: 1a (2 mmol), 2 (1 mmol), (3) (1 mmol) and [DBN][HSO4] under microwave irradiation. bIsolated yield. |
Furthermore, we also studied the power level of microwave effect on model reactions according to these study better results of the desired product when reaction carried at 280 W (Table 3, entry 3). Detailed reaction conditions are shown in Table 3.
Table 3: Optimization of reaction condition for the synthesis of 4a under microwave set upa
Entry |
Power levels in Watt |
Timeb (min) |
Yieldc |
1 |
140 |
20 |
56 |
2 |
210 |
15 |
68 |
3 |
240 |
12 |
84 |
4 |
280 |
10 |
95 |
5 |
350 |
10 |
95 |
aReaction conditions: 1a (2 mmol), 2 (1 mmol) and 3 (1 mmol) in the presence of [DBN][HSO4] 20 mol% under microwave irradiation. bReaction progress monitored by TLC. cIsolated yield.
|
A extremely superlative method to economic and greener preparation is recovery and recyclability of a ionic liquid. Therefore we have to check the efficiency of catalyst after recover from the reaction media during the work-up procedure. When reaction is completed, then reaction mass was pour on ice cold water to obtained fine crystal of final 2-Amino-4H-pyrans derivatives. In the last step removal H2O from filtrate using reduced pressure to gave viscous liquid, which is on cooling to give pure ionic liquid. Recovered catalysts were reused for next four repeated cycles without considerable loss in catalytic efficiency (Table 4).
Table 4: Reusability of [DBN][HSO4] ionic liquid for model reaction
Entry |
Run |
Timea (min) |
Yieldb |
1 |
fresh |
10 |
95 |
2 |
2 |
10 |
95 |
3 |
3 |
10 |
89 |
4 |
4 |
10 |
88 |
5 |
5 |
10 |
82 |
aReaction progress monitered by TLC. bIsolated yield. |
Comparison of [DBN][HSO4] (IL) catalyst with previous reported protocol
We have proved the comparison study of the [DBN][HSO4] with other reported catalysts for the preparation of 2-Amino-4H-pyrans derivative. The comparison results proved that [DBN][HSO4] is better catalyst in terms of excellent yield and reusability with less reaction time (Table 5, entry 10). In conclusion [DBN][HSO4] is found to be a facile and environmentally benign protocol for the synthesis of 2-Amino-4H-pyrans derivatives.
Table 5: Comparative Catalytic Performance of the [DBN][HSO4] with Other Previously Reported Catalysts
Entry |
Catalyst |
Time (min) |
Yield (%) |
solvent/condition |
Ref. |
1 |
MNP-DMAP |
1-3 h |
96 |
Solvent free |
50 |
2 |
Hydroxyapatite or modified sodium apatite |
2-6 h |
61-96 |
Solvent free, r.t |
51 |
3 |
Fe3O4@g C3N4 |
190 min |
80 |
EtOH, 60 °C |
52 |
4 |
KF-Al2O3 |
3 hr |
77 |
EtOH, rt |
53 |
5 |
NH4OAc |
15 min |
78 |
Neat, Grinding |
54 |
6 |
MCM-41@Schiff-based- Co(OAc)2 |
3 h |
93 |
H2O, 50 °C |
45 |
7 |
Nano-ZnO |
3 h |
91 |
EtOH:H2O, rt |
55 |
8 |
TBAF |
30 min |
75 |
Reflux/H2O |
56 |
9 |
DABCO |
2 h |
94 |
Reflux/H2O |
57 |
10 |
PEG 1000-DAIL |
60 |
93 |
Toluene |
58 |
11 |
[DBN][HSO4] |
10 min |
95 |
[DBN][HSO4] act as a solvent |
Present work |
aReaction conditions: 1a (1 mmol), 2 (1 mmol) and 3 (1 mmol) in the presence of [DBN][HSO4] 20 mol% under microwave irradiation. |
The structure of the titled product 4e was confirmed by 1H NMR and 13C NMR. In 1H NMR spectra of compound 4e exhibit two singlet bands for two methyl groups at δ 0.95 and 1.06 ppm. The -CH2-C=O protons observed at δ 2.42 ppm and CH2 proton are observed at δ 2.21-210 ppm suggest that dimedone ring in the final compound. The aliphatic -CH proton was shown at δ 4.66 ppm suggests that formation of cyclic ring in our final compound. In the 13C NMR spectrum of compound 4e, distinct -C=O carbonyl group observed at δ 195.4 ppm. The OCH3, CH, CH2 and CH3 peak observed at δ 54.0, 49.7, 40.8, 32.1, 30.9, 29.2 and 27.2 ppm confirmed that formation of compound 4e.
Scheme 2: Synthesis of 2-Amino-4H-pyrans derivatives (4a-l)
Table 6: [DBN][HSO4] catalyzed synthesis of 2-Amino-4H-pyrans derivativesa
In conclusion, the effectiveness and better reaction time for the model reaction was observed at 280 W by using 20 mol% of [DBN][HSO4] as a catalyst under microwave conditions. With excellent reaction conditions in hand, the adaptableness of this approach was employing the synthesis 2-Amino-4H-pyrans analogues (3a-l). Various substituents on aryl aldehyde including methoxy, methyl, nitro, halogen (-Cl,-Br, -I), and hydroxyl groups were used. Synthesis of compounds (3b-l) using optimized reactions conditions and results are shown in Scheme 2. The result clearly suggest that the condensation reactions using [DBN][HSO4] catalyst shows excellent and remarkable performance irrespective to the electron withdrawing/donating groups present on the aryl aldehydes and hence this method is facile, efficient and general for the synthesis of xanthene analogues. All the synthesized final compounds 3a-l was well characterized by 1H NMR and 13C NMR spectroscopic techniques.
Plausible Reaction Mechanism
Reaction mechanism cycle for the preparation of 2-Amino-4H-pyrans analogues employing [DBN][HSO4] is catalyst. In first step bezaldehyde activated by [DBN][HSO4] results formation intermediate I. In next step [DBN][HSO4] reacts dimedone to give enol product II. In the third step intermediate I reacts with II afforded addition product III. Further formation of alkylation product V from reaction of II and III to via removal of H2O molecule. In the next step intramolecular cyclization of V to give VI. In the last step elimination of H2O molecule using [DBN][HSO4] to results formation of titled 2-Amino-4H-pyrans analogues 4a and regeneration of catalyst. Details reaction mechanism is presented in Scheme 3.
Scheme 3: Reaction mechanism cycle for the preparation of compounds 4a.
Experimental Section
Materials and Methods. All of the reagents used were of laboratory grade. Melting points of all of the synthesized analogues were resolute in an open capillary tube and are
uncorrected. The progress of the reaction was monitored by thin-layer chromatography on Merck’s silica plates, and imagining was accomplished by iodine/ultraviolet light. 1H NMR spectra were recorded with a Bruker AvIII HD-400 MHz spectrometer operating at 400 MHz using DMSO solvent and tetramethylsilane (TMS) as the internal standard and chemical shift in δ ppm. Mass spectra were recorded on a Waters UPLCTQD (ESI-MS and APCI-MS)
instrument, and elemental analysis was recorded on the CHNS auto-analyzer (Thermo Fischer EA1112 SERIES). Chemical shifts (δ) are reported in parts per million using TMS as an internal standard. The splitting pattern abbreviations are designed as singlet (s); doublet (d); double doublet (dd); bs (broad singlet), triplet (t); quartet (q); and multiplets (m).
Preparation of [DBN][HSO4]
General Procedure for the Synthesis of [DBN][HSO4] are given in supporting information.
General Procedure for Synthesis of 2-Amino-4H-pyrans Derivatives
A mixture of aldehyde 1a (1 mmol), 2 dimedone (1 mmol) and 3 malononitrile (1 mmol) in [DBN][HSO4] 20 mol% was stirred under microwave irradiations at 280 W; the evolution of reaction was supervised by thin-layer chromatography [ethyl acetate/n-hexane (3:7)] as a solvent after a stirring reaction mixture was cooled for 15 min and a poured on crushed ice. Thus, acquired solid was filtered, dried, and purified by crystallization using ethanol as a solvent. The synthesis compound is confirmed by MP, 1H NMR and 13C NMR spectra.
2-amino-7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4a)
The compound 4a was synthesized from condensation reaction 1a, 2 and 3 as white solid; Mp: 231-232 οC; Yield: 93%; 1H NMR (500 MHz, cdcl3) δ 7.40 (s, 2H), 7.25 (t, J = 7.6 Hz, 2H), 7.18-7.04 (m, 3H), 4.59 (s, 1H), 2.61-2.07 (m, 4H), 1.11 (dd, J = 60.4, 28.0 Hz, 6H); 13C NMR (101 MHz, cdcl3) δ 195.5, 163.0, 142.2, 136.1, 128.5, 126.5, 118.7, 49.4, 41.2, 31.5, 30.3, 28.5 and 28.3.
2-amino-7,7-dimethyl-5-oxo-4-(m-tolyl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4b)
The compound 4b was synthesized from condensation reaction 1b, 2 and 3 as white solid; Mp: 205-206 οC; Yield: 89%; 1H NMR (400 MHz, cdcl3) δ 7.40 (s, 2H), 7.10-6.92 (m, 3H), 6.83 (d, J = 6.8 Hz, 1H), 4.62 (s, 1H), 2.39 (s, 2H), 2.21 (s, 3H), 2.16-2.13 (m, 2H), 1.01 (s, 3H), 0.91 (s, 3H); 13C NMR (101 MHz, cdcl3) δ 196.4, 167.1, 140.3, 132.2, 128.9, 127.6, 125.2, 122.6, 121.2, 49.1, 39.7, 32.9, 31.1, 28.1, 25.5 and 22.3.
2-amino-7,7-dimethyl-5-oxo-4-(p-tolyl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4c)
The compound 4c was synthesized from condensation reaction 1c, 2 and 3 as yellow solid; Mp: 214-216οC; Yield: 91%; 1H NMR (400 MHz, cdcl3) δ 7.34 (s, 2H), 7.11 (d, J = 7.8 Hz, 2H), 6.95 (d, J = 7.5 Hz, 2H), 4.58 (s, 1H), 2.45 (s, 2H), 2.19 (s, 3H), 2.14-2.04 (m, 2H), 1.02 (s, 3H), 0.91 (s, 3H); 13C NMR (101 MHz, cdcl3) δ 195.3, 161.1, 140.2, 134.6, 127.7, 127.2, 114.6, 49.7, 39.8, 31.1, 30.4, 28.2, 26.3 and 20.0.
2-amino-4-(3-methoxyphenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4d)
The compound 4d was synthesized from condensation reaction 1d, 2 and 3 as pale yellow solid; Mp: 196-198 οC; Yield: 87%; 1H NMR (400 MHz, cdcl3) δ 7.38 (s, 2H), 7.01 (t, J = 8.1 Hz, 1H), 6.75 (d, J = 6.8 Hz, 2H), 6.52 (d, J = 7.0 Hz, 1H), 4.52 (s, 1H), 3.64 (s, 3H), 2.40 (s, 2H), 2.05 (q, J = 16.5 Hz, 2H), 1.00 (s, 3H), 0.88 (s, 3H); 13C NMR (101 MHz, cdcl3) δ 195.2, 161.3, 158.2, 144.6, 127.7, 119.7, 114.4, 113.2, 110.7, 54.0, 49.7, 39.7, 31.0, 30.7, 28.1, 26.2.
2-amino-4-(4-methoxyphenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4e)
The compound 4e was synthesized from condensation reaction 1e, 2 and 3 as pale yellow solid; Mp: 195-196 οC; Yield: 92%; 1H NMR (400 MHz, cdcl3) δ 7.36 (s, 2H), 7.18-7.16 (m, 2H), 7.72-7.70 (m, 2H), 4.66 (s, 1H), 3.68 (s, 3H), 2.42 (s, 2H), 2.21-2.10 (m, 2H), 1.06 (s, 3H), 0.95 (s, 3H); 13C NMR (101 MHz, cdcl3) δ 195.4, 161.0, 156.9, 135.4, 128.2, 114.7, 112.4, 54.0, 49.7, 40.8, 32.1, 30.9, 29.2 and 27.2.
2-amino-4-(3,4-dimethoxyphenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4f)
The compound 4f was synthesized from condensation reaction 1f, 2 and 3 as yellow solid; Mp: 208-210 οC; Yield: 93%; 1H NMR (400 MHz, cdcl3) δ 7.30 (s, 2H), 6.90 (s, 1H), 6.75 (td, J = 8.2, 4.3 Hz, 2H), 4.65 (s, 1H), 3.81 (d, J = 1.8 Hz, 3H), 3.74 (d, J = 1.7 Hz, 3H), 2.40 (s, 2H), 2.23–2.04 (m, 2H), 1.04 (s, 3H), 0.94 (s, 3H); 13C NMR (101 MHz, cdcl3) δ 189.8, 167.5, 153.6, 151.8, 140.6, 131.6, 126.2, 125.6, 119.8, 54.4, 53.6, 49.1, 41.1, 31.8, 29.9, 28.2 and 26.1.
2-amino-7,7-dimethyl-4-(3-nitrophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4g)
The compound 4g was synthesized from condensation reaction 1g, 2 and 3 as red solid; Mp: 213-214οC; Yield: 87%; 1H NMR (400 MHz, cdcl3) δ 8.02–7.85 (m, 2H), 7.74 (d, J = 6.7 Hz, 1H), 7.35 (d, J = 7.8 Hz, 1H), 7.28 (s, 2H), 4.78 (s, 1H), 2.45 (s, 2H), 2.14 (q, J = 16.1 Hz, 2H), 1.04 (s, 3H), 0.94 (s, 3H), 13C NMR (101 MHz, cdcl3) δ 196.4, 166.9, 146.5, 140.4, 130.5, 127.5, 126.2, 124.8, 119.6, 50.9, 40.6, 31.9, 30.2, 28.5 and 26.1.
92-amino-4-(3-iodophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4h)
The compound 4h was synthesized from condensation reaction 1h, 2 and 3 as red solid; Mp: 270-272 οC; Yield: 90%; 1H NMR (400 MHz, cdcl3) δ 7.51 (s, 1H), 7.39 (d, J = 7.8 Hz, 1H), 7.38 (s, 2H), 7.28 (d, J = 7.6 Hz, 1H), 6.84 (t, J = 7.8 Hz, 1H), 4.54 (s, 1H), 2.39 (s, 2H), 2.26–2.07 (m, 2H), 1.05 (s, 3H), 0.94 (s, 3H); 13C NMR (101 MHz, cdcl3) δ 190.0, 164.8, 139.4, 131.5, 128.0, 126.6, 126.3, 122.8, 111.4, 49.4, 40.5, 32.0, 29.9, 28.2 and 26.4.
2-amino-4-(4-bromophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4i)
The compound 4i was synthesized from condensation reaction 1i, 2 and 3 as red solid; Mp: 202-204 οC; Yield: 91%; 1H NMR (400 MHz, cdcl3) δ 7.42 (s, 2H), 7.30 (d, J = 6.9 Hz, 2H), 7.15 (d, J = 6.8 Hz, 2H), 4.61 (s, 1H), 2.41 (s, 2H), 2.18 (q, J = 16.4 Hz, 4H), 1.08 (s, 3H), 0.95 (s, 3H). 13C NMR (101 MHz, cdcl3) δ 195.2, 161.4, 142.1, 130.0, 129.1, 119.1, 114.1, 49.6, 39.8, 31.1, 30.5, 28.2 and 26.2.
2-amino-4-(4-chlorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4j)
The compound 4j was synthesized from condensation reaction 1j, 2 and 3 as pale yellow solid; Mp: 209-211 οC; Yield: 92%; 1H NMR (400 MHz, cdcl3) δ 7.42 (s, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.18–7.11 (m, 2H), 4.68 (s, 1H), 2.42 (s, 2H), 2.15 (q, J = 16.3 Hz, 4H), 1.07 (s, 3H), 0.95 (s, 3H). 13C NMR (101 MHz, cdcl3) δ 195.2, 161.4, 141.7, 130.9, 128.7, 127.1, 114.1, 49.6, 39.7, 31.1, 30.4, 28.2 and 26.2.
2-amino-4-(4-hydroxyphenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4k)
The compound 4k was synthesized from condensation reaction 1k, 2 and 3 as red solid; Mp: 204-206 οC; Yield: 85%; 1H NMR (400 MHz, cdcl3) δ 7.31 (s, 1H), 7.06 (d, J = 7.8 Hz, 2H), 6.54 (d, J = 7.8 Hz, 2H), 4.66 (s, 1H), 2.46 (s, 4H), 2.21 (q, J = 16.4 Hz, 4H), 1.08 (s, 6H), 0.99 (s, 6H). 13C NMR (101 MHz, cdcl3) δ 196.3, 161.4, 153.7, 134.4, 128.2, 114.8, 114.2, 49.7, 39.8, 31.2, 29.9, 28.1 and 26.3.
2-amino-7,7-dimethyl-4-(4-nitrophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4l)
The compound 4l was synthesized from condensation reaction 1l, 2 and 3 as white solid; Mp: 177-178 οC; Yield: 84%; 1H NMR (400 MHz, cdcl3) δ 7.67 (s, 2H), 5.46 (s, 1H), 3.31 (s, 2H), 2.50 (s, 4H), 2.23 (s, 4H), 1.22 (s, 1H), 1.03 (d, J = 18.0 Hz, 12H); 13C NMR (101 MHz, cdcl3) δ 192.3, 164.5, 110.7, 49.4, 39.7, 33.5, 32.0, 30.2, 28.2, 26.4, 24.9, 23.5, 22.2, 22.1 and 22.0.
CONCLUSION
In conclusion, an environmentally and highly efficient green methodology has been established for the synthesis of functionalized 2-Amino-4H-pyrans derivatives using an inexpensive and recoverable [DBN][HSO4] catalytic solvent-free under microwave irradiations. This, to the best of our knowledge, has no examples. This reaction scheme exposes a number of advantages, such as uniqueness, high atom efficiency, mild reaction conditions, clean reaction profiles,
easy workup procedure and Eco friendliness. Furthermore, the prevention of hazardous organic solvents during the entire procedure (synthesis, ionic liquid preparation, and workup
procedure) makes it a convenient and attractive method for the synthesis of these important compounds.
CONFLICT OF INTEREST
The authors declare no conflict of interest, financial or otherwise.
ACKNOWLEDGMENTS
The author V.U.M. are very much grateful to Authority of Department of Chemistry, Dr Babasaheb Ambedkar Marathwada University Aurangabad for providing laboratory facility. The authors are also thankful to the Principal, Shri Chhatrapati Shivaji College, Omerga and Principal R.N.C. Arts, J.D.B. Commerce & N.S.C. Science College, Nashik-Road, Nashik for providing support and necessary all research facilities during my research.
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