DMAP-catalyzed Efficient and Convenient Approach for the Synthesis of 3,3′-(Arylmethylene)bis(2-Hydroxynaphthalene-1,4-Dione) Derivatives

Abstract

For the first time the 4-dimethylaminopyridine (DMAP) catalyzed straightforward and efficient procedure has been developed for the synthesis of 3,3′-(arylmethylene)bis(2-hydroxynaphthalene-1,4-dione) derivatives starting from lawsone (2-hydroxy-1,4-naphthoquinone) and a variety of (hetero)aromatic aldehydes in ethanol under microwave irradiation. Three of nine synthesized compounds are new. This method provides notable advantages over existing procedures including use of non-traditional basic catalyst and environmentally benign solvent, mild reaction conditions, excellent yields, short reaction time and simple workup.

Keywords

nAphthoquinone (hetero)aromatic aldehydes 4-dimethylaminopyridine catalyzed synthesis lawsone.

Introduction

2-Hydroxy-1,4-naphthoquinone (lawsone or hennotannic acid, 1), isolated from the extract of dried powdered leaves of henna (Lawsonia spp., family Lythraceae), is one of the simplest naturally occurring 1,4-naphthoquinones. Lawsone and its isomeric forms including lapachol, parvaquone, atovaquone have been known as lead compounds with a variety of valuable biological activities.¹ The hydroxyl group in lawsone and its derivatives is essential for their biological activities as it affects their redox potentials and prooxidant activities.^2,3 Till now, a variety of lawsone-containing compounds were synthesized, among which, 3,3′-(arylmethylene)bis(2-hydroxynaphthalene-1,4-diones) have received much attention in medicinal chemistry. These bis(2-hydroxy-naphthalene-1,4-dione) derivatives significantly inhibited the proliferation of different human cancer cell lines in a dose-dependent manner and exhibited relatively much lower toxicity in normal cells compared to cisplatin.⁴ Particularly, trifluoromethyl-substituted compound induced apoptosis in the glioma cells by inducing the caspase dependent apoptotic pathways via ROS and downregulating the PI3 K/AKT/mTOR pathway. Several bis-lawsone derivatives were found to exhibit antioxidant, antifungal,⁵ antibacterial,⁶ and antileishmanial activities⁷ as well as inhibit against HIV-1 integrase,⁸ and H5N1 neuraminidase.⁹

Due to the broad biological relevance of 3,3´-(arylmethylene)bis(2-hydroxynaphthalene-1,4-diones), considerable efforts have been paid on the improvement of synthetic approaches of this class of compounds for the past decades. Literature methods are mostly based on acid-catalyzed condensation between lawsone and aldehydes using LiCl,^10,11 sulfuric acid,¹² sulfamic acid,¹³ camphor sulfonic acid,¹⁴ β-alanine/AcOH,⁷ L-aminoacids,⁶ and ionic liquilds¹⁵ as catalyst. Several bio-derived catalysts such as lipase,¹⁶ chitosan, and O-carboxymethyl chitosan¹⁷ were employed in these reactions. However, the use of basic catalyst in the synthesis of bis-lawsone compounds have rarely been studied.¹⁸ In recent times, 4-dimethylaminopyridine (DMAP) is well known as an outstanding catalyst for various synthetic transformations.^19,20 The catalytic efficiency of DMAP is probably based on steric effects, the donor ability of the amine substituent, the good nucleophilic properties, and stabilization of pyridinium ion.¹⁹ In that respect, considering the important bioactivities of 3,3´-(arylmethylene)bis(2-hydroxynaphthalene-1,4-dione) derivatives and reported reaction conditions for their synthesis, herein, we describe the synthesis of this class of compounds from lawsone (1) and (hetero)aromatic aldehydes 2a-i using DMAP as a catalyst. To the best of our knowledge, it is reported for the first time that this condensation reaction can be catalyzed by organic base DMAP.

2. Result and Discussion

In our initial investigation, the synthesis of 3,3'-(4-chloromethylene) bis(2-hydroxynaphthalene-1,4-dione) 3a starting from lawsone (1) (2 equiv) and 4-chlorobenzaldehyde (2a) (1 equiv) was chosen for screening optimal reaction conditions. Several base including triethylamine Et₃N, DMAP, pyridine and 1,4-diazabicyclo[2.2.2]octane (DABCO) were employed as catalyst in this study. Microwave irradiation (MW) has been known as a modern technique provide many notable advantages such as reduction of side reactions, shortening reaction time and improving reaction yields.²¹ In this study, MW technique was applied to perform our experiments. The results were summarized in Table 1. No expected product was found in the case of using Et₃N in ethanol at room temperature under MW (entry 1). While increasing reaction temperature to reflux, compound 3,3'-(4-chloromethylene)bis(2-hydroxynaphthalene-1,4-dione) (3a) was detected by TLC in trace quantity (entry 2). It is important to note that the use of Et₃N as catalyst gave the ammonium salt of products.^18,22 Replacing Et₃N with pyridine or DABCO resulted compound 3a in 38 to 59% isolated yields (entries 3, 4). The reaction yield increased significantly to 91% when DMAP was used (entry 5). Evidently, DMAP was an effective base-catalyst for this reaction, therefore, DMAP was chosen for further study.

Table 1.
Screening of the Catalyst and Solvent for the Synthesis of Compound 3,3'-(4-Chloromethylene) bis(2-Hydroxynaphthalene-1,4-Dione) 3a.

Entry Catalyst Reaction conditions Isolated yields (%)^a,b

1 Et₃N (20 mol%) EtOH, MW, rt, 30 min 0

2 Et₃N (20 mol%) EtOH, MW, reflux, 30 min trace

3 Pyridine (20 mol%) EtOH, MW, reflux, 30 min 38

4 DABCO (20 mol%) EtOH, MW, reflux, 30 min 59

5 DMAP (20 mol%) EtOH, MW, reflux, 15 min 96

6 DMAP (20 mol%) CH₃CN, MW, reflux, 15 min 65

7 DMAP (20 mol%) Water, MW, reflux, 15 min trace

8 DMAP (20 mol%) EtOH/H₂O (1:1), MW, reflux, 15 min 71

9 DMAP (10 mol%) EtOH, MW, reflux, 30 min 63

10 DMAP (30 mol%) EtOH, MW, reflux, 15 min 91

11 DMAP (20 mol%) EtOH, reflux, 60 min 57^c

Entry	Catalyst	Reaction conditions	Isolated yields (%)^a,b
1	Et₃N (20 mol%)	EtOH, MW, rt, 30 min	0
2	Et₃N (20 mol%)	EtOH, MW, reflux, 30 min	trace
3	Pyridine (20 mol%)	EtOH, MW, reflux, 30 min	38
4	DABCO (20 mol%)	EtOH, MW, reflux, 30 min	59
5	DMAP (20 mol%)	EtOH, MW, reflux, 15 min	96
6	DMAP (20 mol%)	CH₃CN, MW, reflux, 15 min	65
7	DMAP (20 mol%)	Water, MW, reflux, 15 min	trace
8	DMAP (20 mol%)	EtOH/H₂O (1:1), MW, reflux, 15 min	71
9	DMAP (10 mol%)	EtOH, MW, reflux, 30 min	63
10	DMAP (30 mol%)	EtOH, MW, reflux, 15 min	91
11	DMAP (20 mol%)	EtOH, reflux, 60 min	57^c

Reagents and conditions: 1 (0.5 mmol), 2a (0.25 mmol), catalyst, solvent (10 ml), MW, 15 to 30 min.

Isolated yields.

Oil bath.

As shown in Table 1 (entries 5-8), water was not appropriate solvent for this reaction, meanwhile product 3a were obtained in moderate yields (65% and 71%) when the reaction was performed in CH₃CN or EtOH/H₂O (1:1). The highest yield of 3a was achieved by using ethanol as the reaction media (entry 5).

The effect of the amount of DMAP on the yield has also been investigated. The results revealed that the use of lower amount of DMAP (10 mol%) required a longer reaction time to furnish a comparable result (entry 9). At the same time, the yield was not further improved when an excess amount of catalyst (30 mol%) was loaded (entry 10). It is clear from the results, that 20 mol% of DMAP is sufficient to achieve the optimum yield of the product (entry 5).

Furthermore, a comparison of the effect of DMAP and other catalysts, previously reported on the synthesis of compound 3a, was shown in Table 2 representing DMAP as an alternative effective catalyst for this reaction. We also examined the reaction under conventional thermal heating conditions and compound 3a was obtained in 57% yield (Table 1, Entry 11). According to these results, DMAP (20 mol%) in ethanol at reflux under MW came out as the optimized conditions in terms of yield and time for the synthesis of compound 3a (Table 2, entry 6).

Table 2.

Effect of DMAP and Other Catalyst on the Synthesis of Compound 3a.

Entry	Catalyst	Reaction conditions	Yield (%)
1	LiCl	H₂O, reflux, 12 h	91⁹
2	H₂SO₄	EtOH/H₂O (1:1), reflux, 30 min	93¹⁰
3	Sulfamic acid	EtOH/H₂O (1:1), rt, 19 h	89¹¹
4	Lipase	EtOH, 60 C, 2 h	92.1¹⁴
5	O-carboxy-methyl chitosan	H₂O, 70 C, 45 to 60 min	94¹⁵
6	DMAP	EtOH, MW, reflux, 15 min	96

To demonstrate the efficiency and scope of the present procedure, the above optimized reaction conditions were applied to various benzaldehydes with electron-withdrawing groups (such as halogen, trifluoromethyl group) or electron-donating groups (including methyl, methoxy, phenyl) as well as heteroaromatic aldehydes (piperonal, pyridine-3-carbaldehyde, benzo[b]thiophene-2-carbaldehyde) to give good to excellent yields of the corresponding products (86%–96%) (Scheme 1). The chemical structures of compounds 3a-i were determined by HRMS, ¹H NMR, and ¹³C NMR spectra (see Supplemental aterial Figures S1-S27). The characterization of these compounds 3a-f agrees with published data.^12-17 Compounds 3g, 3h, and 3i are new ones. On analyzing the ¹H NMR spectra, in general, a singlet at around δ 6.65 to 6.75 ppm corresponded to the aliphatic hydrogen H-9, confirming the synthesis of the compounds. Two doublets in the region of lower chemical shift (7.85-8.00 ppm) with a coupling constant of 7.2 Hz were assigned to protons H-5 and H-8, meanwhile two doublets of triplets at 7.75 and 7.67 ppm were identified as protons H-6 and H-7 of the naphthoquinone ring. In the ¹³C NMR analysis, the number of signals does not correspond directly to the number of carbon atoms present in the structure due to the symmetry of the compounds. Signals of naphthoquinone carbonyl carbons appeared at 182 to 183 ppm, while enolic carbon (C-2) and sp³ carbon (C-9) were assigned at around 155 to 163 ppm and 32 to 33 ppm, respectively.

Scheme 1.

Synthesis of compounds 3a-3i.

The formation of 3,3'-(arylmethylene)bis(2-hydroxynaphthalene-1,4-diones) 3a-i could be explained by proposed mechanism described in Scheme 2. It is supposed that initially DMAP catalyzed the Knoevenagel condensation between lawsone (1) and aldehyde 2 to give intermediate 5, which underwent dehydration to furnish 3-(1-arylmethylidene)-1,2,3,4-tetrahydro-12,4-naphthalenetrione (6). The naphthalenetrione (6) reacted in a Michael manner with the second molecule of lawsone (1) under DMAP-catalysis to generate the intermediate 7, followed by elimination of DMAP catalyst and tautomerization to afford product 3a-i.

Scheme 2.

Proposed reaction mechanism.

3. Materials and Methods

3.1. General Experimental Procedures

All reagents and solvents were purchased from Aldrich or Merck unless noted otherwise. Solvents were used directly as purchased unless otherwise indicated. The reaction was carried out in Anton Paar Microwave Synthetic Reactor Monowave 400. TLC was performed using Merck silica gel 60 F₂₅₄ and visualized under UV light at 254 nm to check the progress of reactions and preliminary evaluation of compounds’ homogeneity. Purification of compounds was carried out using open silica gel column flash chromatography with Merck silica gel 60 (240-400 mesh) as stationary phase. Melting points were determined using a Buchi B-545 melting point apparatus and are uncorrected. IR analysis was recorded on Perkin Elmer Spectrum Two spectrometer in KBr pellet. ¹H and ¹³C NMR spectra were recorded on a Bruker Avance III spectrometer (600 and 150 MHz, respectively) in DMSO-d₆. TMS was used as internal standard. HRMS were recorded on a SCIEX X500 QTOF mass spectrometer in ESI + or ESI– mode.

3.2. Preparation of Compounds 3a-i

A vial containing a mixture of 2-hydroxy-1,4-naphthoquinone 1 (87.1 mg, 0.5 mmol), aldehyde 2 (0.25 mmol) and DMAP (61 mg, 0.05 mmol) in 5 ml ethanol was sealed and placed in an Anton Paar Microwave Synthetic Reactor. The vial was subjected to microwave irradiation, programmed at 98 ^oC and 150 W. After a period of 30 s, the temperature reached a plateau, 98 ^oC, and remained constant. After completion of the reaction (15-20 min), the vial was cooled to room temperature. Solvent was evaporated, and the residue was washed with water and ethanol. The crude products were further purified by recrystallization from ethanol (95%) to afford pure compounds 3a-i.

3.2.1. 3,3'-([4-Chlorophenyl]methylene)bis(2-hydroxynaphthalene-1,4-dione) (3a)

Reaction time 15 min. Yellow powder. Mp. 196 to 198 ^oC (198-200 C).¹⁷ Yield 96%. IR (KBr) cm⁻¹: 3445, 2909, 1651, 1615, 1591, 1488, 1462, 1371, 1342, 1281, 1221, 1092, 1062, 1014, 915, 832, 788, 733. ¹H NMR (DMSO-d₆, 600 MHz), δ (ppm): 7.97 (2H, d, J = 7.2 Hz), 7.88 (2H, d, J = 7.2 Hz), 7.76 (2H, td, J = 7.8 Hz, J = 1.2 Hz), 7.67 (2H, td, J = 7.2 Hz, J = 1.2 Hz), 7.20 (2H, d, J = 8.4 Hz), 7.14 (2H, d, J = 8.4 Hz), 6.67 (1H, s). ¹³C NMR (DMSO-d₆, 150 MHz), δ: 183.6, 182.3, 161.7, 140.5, 133.8, 133.2, 131.9, 130.9, 129.3, 128.7 (2C), 127.6 (2C), 125.7, 125.1, 122.0, 32.6. HRMS: Found m/z 493.0451 [M + Na]⁺, calcd. for C₂₇H₁₅ClO₆Na: 493.0455.

3.2.2. 3,3'-([4-Bromophenyl]methylene)bis(2-hydroxynaphthalene-1,4-dione) (3b)

Reaction time 15 min. Yellow powder. Mp 213 to 215 C (214-216 C).¹² Yield 91%. IR (KBr) cm⁻¹: 3452, 3076, 2909, 1647, 1595, 1571, 1484, 1371, 1282, 1222, 1062, 1008, 968, 914, 827, 731. ¹H NMR (DMSO-d₆, 600 MHz), δ: 7.96 (2H, d, J = 7.2 Hz), 7.88 (2H, d, J = 7.2 Hz), 7.76 (2H, td, J = 1.2 Hz, J = 7.8 Hz), 7.67 (2H, td, J = 1.2 Hz, J = 7.8 Hz), 7.33 (2H, d, J = 8.4 Hz), 7.08 (2H, d, J = 8.4 Hz), 6.64 (1H, s). ¹³C NMR (DMSO-d₆, 150 MHz), δ (ppm): 183.5, 182.7, 141.1, 133.8, 133.2, 131.9, 130.9, 130.5, 129.2, 125.7, 125.1, 122.0, 117.7, 33.7. HRMS: Found m/z 515.0132 [M(⁷⁹Br) + H]⁺, calcd. for C₂₇H₁₆⁷⁹BrO₆: 515.0130; m/z 517.0117 [M(⁸¹Br) + H]⁺, calcd. for C₂₇H₁₆⁸¹BrO₆: 517.0110.

3.2.3. 3,3'-([4-[Trifluoromethyl]phenyl]methylene)bis(2-hydroxy-naphthalene-1,4-dione) (3c)

Reaction time 15 min. Yellow powder. Mp 188 to 191 C (188-190 C).¹² Yield 92%. IR (KBr) cm⁻¹: 3434, 2911, 1676, 1643, 1599, 1572, 1327, 1280, 1162, 1116, 1068, 1026, 968. ¹H NMR (DMSO-d₆, 600 MHz), δ (ppm): 7.98 (2H, d, J = 7.8 Hz), 7.89 (2H, d, J = 7.2 Hz), 7.77 (2H, t, J = 7.2 Hz), 7.68 (2H, t, J = 7.2 Hz), 7.51 (2H, d, J = 8.4 Hz), 7.35 (2H, d, J = 7.8 Hz), 6.75 (1H, s). ¹³C NMR (DMSO-d₆, 150 MHz), δ: 183.5, 182.3, 160.4, 146.8, 133.8, 133.2, 132.0, 130.9, 127.6, 125.8, 125.5, 125.2, 124.6, 121.8, 33.2. HRMS: Found m/z 527.0722 [M + Na]⁺, calcd. for C₂₈H₁₅F₃O₆Na: 527.0718.

3.2.4. 3,3'-(p-Tolylmethylene)bis(2-hydroxynaphthalene-1,4-dione) (3d)

Reaction time 20 min. Yellow powder. Mp 170 to 172 C (174-176 C).¹² Yield 94%. IR (KBr) cm⁻¹: 3435, 2913, 1654, 1604, 1592, 1508, 1461, 1372, 1341, 1282, 1222, 1189, 1057, 1024, 914, 805, 762, 731, 689. ¹H NMR (DMSO-d₆, 600 MHz), δ (ppm): 7.96 (2H, d, J = 7.2, Hz), 7.87 (2H, d, J = 7.2 Hz), 7.75 (2H, td, J = 7.2 Hz, J = 1.2 Hz), 7.67 (2H, td, J = 7.2 Hz, J = 1.2 Hz), 6.99 (2H, d, J = 7.8 Hz), 6.95 (2H, d, J = 8.4 Hz), 6.64 (1H, s), 2.22 (3H, s). ¹³C NMR (DMSO-d₆, 150 MHz), δ: 183.7, 161.9, 138.3, 133.7, 133.4, 133.3, 131.8, 130.9, 128.3, 126.7, 125.7, 125.0, 122.6, 32.6, 20.5. HRMS: Found m/z 451.1179 [M + H]⁺, calcd. for C₂₈H₁₉O₆: 451.1182.

3.2.5. 3,3'-([3-Methoxyphenyl]methylene)bis(2-hydroxynaphthalene-1,4-dione) (3e)

Reaction time 18 min. Yellow powder. Mp 186 to 187 ^oC (185-187 ^oC¹⁰). Yield 90%. IR (KBr) cm⁻¹: 3437, 2925, 1672, 1640, 1599, 1572, 1484, 1361, 1283, 1156, 1093, 1047, 970, 913, 825, 739.

¹H NMR (DMSO-d₆, 600 MHz), δ: 7.96 (2H, d, J = 7.8 Hz), 7.88 (2H, d, J = 7.2 Hz), 7.76 (2H, t, J = 7.8 Hz), 7.67 (2H, t, J = 7.8 Hz), 7.08 (1H, d, J = 7.8 Hz), 6.71 to 6.63 (4H, m), 3.62 (3H, s). ¹³C NMR (DMSO-d₆, 150 MHz), δ (ppm): 183.7, 182.4, 159.0, 143.1, 133.8, 133.3, 131.9, 130.9, 128.6, 125.7, 125.1, 122.4, 119.4, 113.3, 109.5, 54.7, 33.0. HRMS: Found m/z 467.1141 [M + H]⁺, calcd. for C₂₈H₁₉O₇: 467.1131.

3.2.6. 3,3'-([Naphthalen-2-yl]methylene)bis(2-hydroxynaphthalene-1,4-dione) (3f)

Reaction time 20 min. Yellow powder. Mp 249 to 252 C (248-250 C).¹³ Yield 90%. IR (KBr) cm⁻¹: 3449, 3057, 2907, 1634, 1607, 1590, 1575, 1524, 1368, 1343, 1284, 1222, 1162, 965. ¹H NMR (DMSO-d₆, 600 MHz), δ (ppm): 7.99 (2H, d, J = 7.8 Hz), 7.91 (2H, d, J = 7.8 Hz), 7.80 to 7.74 (4H, m), 7.69 (3H, m), 7.60 (1H, br. s), 7.39 to 7.37 (2H, m), 7.30 (1H, d, J = 9.0 Hz), 6.84 (1H, s). ¹³C NMR (DMSO-d₆, 150 MHz), δ: 183.7, 182.5, 157.2, 139.1, 133.8, 133.3, 133.1, 131.9, 131.3, 131.0, 127.4, 127.1, 127.08, 126.3, 125.8, 125.5, 125.1, 124.7, 124.4, 122.3, 33.4. HRMS: Found m/z 487.1172 [M + H]⁺, calcd. for C₃₁H₁₉O₆: 487.1182.

3.2.7. 3,3'-(Benzo[d][1,3]dioxol-5-ylmethylene)bis(2-hydroxynaphthalene-1,4-dione) (3g)

Reaction time 18 min. Yellow powder. Mp 217 to 218 C. Yield 89%. IR (KBr) cm⁻¹: 3427, 2918, 1640, 1599, 1570, 1485, 1434, 1355, 1281, 1235, 1026. ¹H NMR (DMSO-d₆, 600 MHz), δ (ppm): 7.95 (2H, d, J = 7.8 Hz), 7.87 (2H, d, J = 7.8 Hz), 7.75 (2H, td, J = 1.2 Hz, J = 7.8 Hz), 7.66 (2H, td, J = 1.2 Hz, J = 7.8 Hz), 6.68 (1H, d, J = 8.4 Hz), 6.64 (1H, d, J = 1.8 Hz), 6.58 (1H, s), 6.61 (1H, d, J = 1.8 Hz), 5.90 (2H, s). ¹³C NMR (DMSO-d₆, 150 MHz), δ (ppm): 183.7, 157.8, 147.0, 144.6, 135.4, 133.8, 133.3, 131.9, 131.0, 125.8, 125.2, 119.6, 107.6, 107.5, 100.5, 32.8. HRMS: Found m/z 503.1100 [M + Na]⁺, calcd. for C₂₈H₁₆O₈Na: 503.0743.

3.2.8. 3,3'-(Pyridin-3-ylmethylene)bis(2-hydroxynaphthalene-1,4-dione) (3h)

Reaction time 20 min. Yellow powder. Mp 218 to 219 ^oC. Yield 88%. IR (KBr) cm⁻¹: 3447, 3057, 2887, 1672, 1641, 1597, 1572, 1459, 1366, 1277, 1255, 1118, 1010, 965, 938, 861. ¹H NMR (DMSO-d₆, 600 MHz), δ (ppm): 8.68 (1H, s), 8.61 (1H, d, J = 4.8 Hz), 8.24 (1H, d, J = 7.8 Hz), 7.97 (2H, d, J = 7.8 Hz), 7.93 (2H, d, J = 7.2 Hz), 7.79 (2H, t, J = 7.8 Hz), 7.76 to 7.70 (3H, m), 6.63 (1H, s). ¹³C NMR (DMSO-d₆, 150 MHz), δ (ppm): 182.6, 182.4, 162.7, 142.8, 142.5, 140.7, 134.0, 132.9, 132.3, 130.8, 125.8, 125.5, 125.3, 120.5, 32.4. HRMS: Found m/z 436.0818 [M-H]⁻, calcd. for C₂₈H₁₄NO₆: 436.0821.

3.2.9. 3,3'-(Benzo[b]thiophen-2-ylmethylene)bis(2-hydroxynaphthalene-1,4-dione) (3i)

Reaction time 18 min. Yellow powder. Mp 174 to 175 ^oC. Yield 86%. IR (KBr) cm⁻¹: 3427, 3070, 2919, 1672, 1641, 1597, 1571, 1458, 1427, 1334, 1278, 1157, 1024, 1004, 966, 902, 823. ¹H NMR (DMSO-d₆, 600 MHz), δ (ppm): 7.99 (2H, d, J = 7.8 Hz), 7.88 (3H, t, J = 7.2 Hz), 7.77 (2H, dt, J = 1.2 Hz, J = 7.2 Hz), 7.67 (2H, t, J = 7.2 Hz), 7.46 (1H, d, J = 7.8 Hz), 7.29 (1H, d, J = 1.2 Hz), 7.24 (1H, t, J = 7.2 Hz), 7.19 (1H, t, J = 7.8 Hz), 6.85 (1H, s). ¹³C NMR (DMSO-d₆, 150 MHz), δ (ppm): 183.6, 182.2, 139.9, 138.6, 135.0, 133.9, 133.2, 132.0, 130.9, 125.9, 125.2, 123.7, 123.6, 122.9, 122.7, 121.6, 29.3. HRMS: Found m/z 491.0592 [M-H]⁻, calcd. for C₂₉H₁₅O₆S: 491.0589.

4. Conclusions

In conclusion, 4-dimethylaminopyridine (DMAP) for the first time was used as catalyst for the efficient synthesis of 3,3′-(arylmethylene)bis(2-hydroxynaphthalene-1,4-dione) derivatives. This DMAP-catalyzed condensation reactions between 2-hydroxy-1,4-naphthoquinone 1 and (hetero)aromatic aldehydes 2 were performed in ethanol under microwave irradiation at reflux for 15 to 20 min. Compounds 3g, 3h, 3i are newly synthesized compounds. The use of non-traditional base catalyst, environmentally benign solvent, mild reaction conditions, excellent yields, short reaction times and simple workup are achievements of this developed procedure.

Supplemental Material

sj-doc-1-npx-10.1177_1934578X211045808 - Supplemental material for DMAP-catalyzed Efficient and Convenient Approach for the Synthesis of 3,3′-(Arylmethylene)bis(2-Hydroxynaphthalene-1,4-Dione) Derivatives

Supplemental material, sj-doc-1-npx-10.1177_1934578X211045808 for DMAP-catalyzed Efficient and Convenient Approach for the Synthesis of 3,3′-(Arylmethylene)bis(2-Hydroxynaphthalene-1,4-Dione) Derivatives by Le Nhat Thuy Giang, Dang Thi Tuyet Anh, Hoang Thi Phuong, Nguyen Ha Thanh, Nguyen Thi Quynh Giang, Nguyen Tuan Anh, Nguyen Van Tuyen and Phan Van Kiem in Natural Product Communications

Footnotes

Acknowledgments

This research is funded by the Vietnamese National Foundation for Science and Technology Development (NAFOSTED, code: 104.01-2020.09).

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Vietnamese National Foundation for Science and Technology Development (NAFOSTED). (grant number 104.01-2020.09).

Trial Registration

Not applicable, because this article does not contain any clinical trials.

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This article does not contain any studies with human or animal subjects.

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There are no human subjects in this article and informed consent is not applicable.

Ethical Approval

Our institution does not require ethical approval for reporting individual cases or case series.

ORCID iD

Phan Van Kiem

Supplemental Material

Supplemental material for this article is available online.

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