Conventional and microwave-irradiated synthesis of new bischalcone derivatives

Abstract

A series of 12 novel methyl- and halogen-substituted bischalcones containing an azo linkage was synthesized by a Claisen–Schmidt condensation between (E)-1-{4-[(4-acetyl-2-hydroxyphenyl)diazenyl]phenyl}ethanone and various araldehydes using microwave irradiation and conventional procedures and the results were compared.

Introduction

Chalcone fragments feature widely in both natural and synthetic products. They are significant intermediates in organic synthesis. ¹ Bischalcones are natural products found in the Anacardiacea family. Both biflavonoids and bischalcones are plentiful in the Rhus genus. Rhuschalcones II–VI have been separated from the root bark of Rhus pyroides, and synthetic derivatives have been shown to have vigorous antiplasmodial and moderate antiproliferative and antiprotozoal activities. In addition, Rhuschalcone VI (I) has cytotoxic activity against colon tumour cell lines. In general, naturally occurring bischalcones consist of two chalcone parts linked by either an ether oxygen or one or more carbon bonds.^2–6 Many synthetic bischalcones are composed of two chalcone fragments with various connections such as bi-aryl, di-aryl ether, methylene and carbon chains of varying lengths. Synthetic bischalcones bearing a piperidine ring such as 3,5-bis-(4-boronic acid-benzylidene)-1-methyl-piperidin-4-one (II) showed a more vigorous inhibition of colon cancer cells expressing wild-type p53 than of an isogenic cell line that was p53-null, ⁷ and (E)-3-(2-hydroxy-5-{4-hydroxy-3-[(E)-3-oxo-3-phenyl-1-propenyl]benzyl}phenyl)-1-phenyl-2-propen-1-one (III) with a structure consisting of two chalcones connected by a methylene group has been shown to have antimicrobial activity ⁸ (Figure 1).

Figure 1.

Natural and synthetic bischalcones.

Some natural products, pharmaceuticals, organic functional materials, dyes and significant synthetic intermediates have azo groups in their structures. Some azo analogues demonstrate miscellaneous biological activities, making them of interest to the pharmaceutical industry. It has been reported that they are effective as anti-proliferation agents in lung cancer and as antibacterials and carbonic anhydrase inhibitors.^3,9 Following our recent report of the synthesis of an azo-linked bischalcone with a sulfonamide ¹⁰ and a quinoline ¹¹ and considering the pharmacological importance of both bischalcones and azo compounds, we set out to synthesize a new series of bischalcones possessing different substitution patterns on an azo framework. Here, we describe their synthesis using microwave (MW) irradiation and conventional procedures and compare the results.

Results and discussion

Our starting point for the synthesis of a series of azo-bridged bischalcones was the preparation of the azo-bridged bisacetophenone, (E)-1-{4-[(4-acetyl-2-hydroxyphenyl)diazenyl]phenyl}ethanone (3) which we synthesized by diazotization of p-aminoacetophenone (1) and azo coupling it with 3-hydroxyacetophenone (2) (Scheme 1) according to our earlier reported procedure. ³ Synthesis of bischalcones using the Claisen–Schmidt condensation was to be a cornerstone of our strategy and our plan was to react the azo-bridged bisacetophenone 3 with a variety of araldehydes 4 in EtOH (Scheme 2) both conventionally by heating and by MW irradiation. In order to optimize the reaction conditions, the synthesis of compound 5a (R¹ = Me, R², R³ = H), by reacting 2-methylbenzaldehyde (4a, R¹ = Me, R², R³ = H) with 3 was chosen as a model reaction. Initially, MW irradiation was implemented at different power values of 50, 100, 150, 200 and 250 W and for different lengths of time (the progress of the reaction was monitored by thin-layer chromatography (TLC)). A power of 150 W for 10 min proved optimal.

Scheme 1.

Synthesis of azo-bridged bisacetophenone (3).

Scheme 2.

Synthesis of new bischalcones (5a-l).

We found that a shorter reaction time and a lower or higher MW power gave rise to lower conversion rates, while increasing the reaction time or MW power resulted in fragmentation of the target product, as revealed by TLC analysis. We then used these optimal MW conditions to synthesize 11 other azo-bridged bischalcones (5b–l; R¹, R², R³ = various), and the yields obtained are shown in Table 1. Also featured in Table 1 are the yields of the same reactions using conventional heating. As can be seen from Table 1, when compared to the conventional method, MW irradiation reduced the reaction time from 72 h to 10 min and increased the yields from 65%–82% to 97%–100%.

Table 1.

Yields of azo-bridged chalcones 5a–l prepared from a series of araldehydes 4a–l and an azo-bridged bisacetophenone 3 by a MW and a conventional method.

Entry	Comp.	R1	R2	R3	MW irradiation method a	Conventional method b
					Yield c (%)	Yield c (%)
1	5a	CH3	H	H	99	70
2	5b	H	CH3	H	98	65
3	5c	H	H	CH3	99	70
4	5d	F	H	H	97	72
5	5e	H	F	H	97	68
6	5f	H	H	F	98	71
7	5g	Cl	H	H	98	71
8	5h	H	Cl	H	100	77
9	5i	Cl	H	Cl	98	72
10	5j	Br	H	H	97	82
11	5k	H	Br	H	99	70
12	5l	H	H	Br	100	71

MW: microwave.

a

Reaction conditions: To a stirred mixture of compound 3 (2 mmol) and a substituted benzaldehyde 4a–l (4 mmol) in EtOH (3 mL) in a G-10 process vial capped with a teflon septum, aqueous sodium hydroxide solution (3 mmol) was added slowly and stirred at room temperature for 5 min. Then, the reaction mixture was irradiated for 10 min at 150 W.

b

Reaction conditions: To a stirred mixture of compound 3 (1 mmol) and a substituted benzaldehyde 4a–l (2 mmol) in EtOH (20 mL) was added sodium hydroxide (40%, 5 mL) at 0 °C. Then, the reaction mixture was stirred for 72 h at room temperature.

c

Isolated yields.

An important feature of the structural characterization of chalcones 5a–l is the assignment of the geometric relationship of H_α and H_β. The J values of 15.0/16.0 Hz of H_α and H_β are consistent with a trans relationship at the C=C double bond of the α,β-unsaturated moiety of 5a–l, respectively.^3,10,12

Some other selected spectral data of other compounds are discussed in the following. For compound 5b, the characteristic carbonyl stretching vibration of an α,β-unsaturated group occurred at 1654 cm^–1 and the –N=N– stretching signal appeared at 1584 cm^–1. The ¹H NMR spectrum of 5b shows sharp singlets at δ 2.33 ppm (3H) and 2.28 ppm (3H) which indicates the presence of two methyl protons. The olefinic proton adjacent to the carbonyl group appeared as two doublets at δ 7.42 (A part of AB system, J = 15.6 Hz) and 7.75 ppm (B part of AB system, J = 15.6 Hz), indicative that the ethylene moiety in the enone linkage is in a trans-conformation in the chalcone. The ¹³C NMR spectrum of 5b showed two signals characteristic of α,β-unsaturated carbonyl groups at δ 195.2 and 189.0 ppm. The olefinic carbons appeared at δ 145.7–144.8 and 121.4–120.8 ppm. In addition, ¹H–¹H COSY spectra also contributed to the identification of peaks.

¹H and ¹³C NMR data of all chalcones 5a–l  are given in the ‘Experimental’ section. All compounds showed Fourier-transform infrared spectroscopy (FTIR), ¹H and ¹³C NMR spectra analyses compatible with the assigned structures. Additional support for the structures of the chalcones 5a–l was the appearance of a molecular ion peak at corresponding m/z values confirming their molecular masses.

Conclusion

In conclusion, a novel series of bischalcones linked by an azo group was synthesized using both a conventional and a MW method. The structures of all compounds were confirmed by FTIR, NMR and MS spectral data and elemental analysis.

Experimental

The compounds 4-aminoacetophenone, hydrochloric acid, NaNO₂, 3-hydroxyacetophenone, NaOH, sodium acetate and all aldehydes were obtained from Sigma or Merck and used as received without further purification. All solvents were purchased from Merck and freshly distilled. NMR spectra were obtained on a Varian Mercury spectrometer (¹H NMR at 200 Hz and ¹³C NMR at 50 Hz) in CDCl₃ using tetramethylsilane (TMS) as internal standard. Chemical shifts (δ) are given in ppm and coupling constants (J) are given in hertz (Hz). Mass spectrometric analysis was carried out on an Agilent 1260 Infinity Series quadrupole time-of-flight (Q-TOF) liquid chromatography–mass spectrometry (LC/MS; electrospray ionization (ESI)/MS; for compound 1) and a Micromass Quattro LC-MS/MS spectrometer (for compounds 3, 4 and 5a–l). The elemental analyses were performed on a Costech ESC 4010 instrument. The IR spectra were determined using a PerkinElmer 1600 FTIR–attenuated total reflectance (ATR) spectrophotometer. Melting points were determined using a Barnstead electrothermal 9200 series digital apparatus. All MW experiments were carried out in a dedicated Anton Paar Monowave-300 reactor. Compound 3 was synthesized by a published method. ³ Melting point, FTIR, MS and NMR data of each known compound are consistent with that reported previously. ³

Synthesis of (E)-1-{4-[(4-acetyl-2-hydroxyphenyl)diazenyl]phenyl}ethanone (3)

4-Aminoacetophenone (2 g, 0.0148 mol) was dissolved in 5 × 10^–3 L of concentrated HCl. The solution was cooled down in an ice–salt bath, and then, a cold solution of NaNO₂ (1 g, 0.0148 mol) in 1 × 10^–2 L of water was slowly added. The reaction mixture that resulted was stirred for 3 h at 0–5 °C. The resulting diazonium salt was cooled in an ice–salt bath. 3-Hydroxyacetophenone (2 g, 0.0148 mol) was dissolved in a dilute NaOH solution and cooled in an ice–salt bath, and then, the cold diazonium solution was added to this cooled solution dropwise at 0–5 °C. After stirring the reaction mixture for 4 h, the pH of the reaction mixture was adjusted to 4–5 by the addition of a saturated sodium acetate solution. Subsequently, it was stirred for 2 h. The precipitate was filtered off, dried and recrystallized from EtOH/H₂O (1:1): yield (4.10 g), m.p. 206–207 °C (lit. ³ 206–207 °C).

Conventional method for synthesis of chalcones 5a–l

(E)-1-{4-[(4-Acetyl-2-hydroxyphenyl)diazenyl]phenyl}ethanone (3) (2 mmol) and a substituted benzaldehyde (4 mmol) were dissolved in ethanol (20 mL). To this mixture, sodium hydroxide (40%, 5 mL) was added at 0–5 °C. The reaction mixture was stirred at the same temperature for 72 h. The progress of the reaction was monitored by TLC. Then, this reaction mixture was poured over crushed ice and acidified with dilute HCl. The dark red solid thus obtained was filtered off, washed with water, dried and crystallized from EtOH/H₂O (1:1).

MW method for synthesis of chalcones 5a–l

(E)-1-{4-[(4-Acetyl-2-hydroxyphenyl)diazenyl]phenyl}ethanone (3) (1 mmol) and an aldehyde (2 mmol) were dissolved in a G-10 vial in absolute ethanol (3 mL). To this, aqueous sodium hydroxide solution (3 mmol) was added slowly and stirred at room temperature for 5 min. Then, the reaction mixture was MW irradiated for about 10 min at 150 W. The reactions were monitored through TLC. After completion of the reaction, the mixture was cooled in an ice–water bath until solids formation was completed. The crude product was filtered off. The dark red solid was washed with cold water to remove the sodium hydroxide and recrystallized from EtOH/H₂O (1:1) twice to give crystals.

(E)-1-{3-Hydroxy-4-[(E)-{4-[(E)-3-o-tolylacryloyl]phenyl}diazenyl]phenyl}-3-o-tolylprop-2-en-1-one (5a): Dark red crystals; yield 0.45 g (70%); m.p. 93–95 °C; FTIR (KBr, cm^–1): 3223, 3067, 1641, 1585; ¹H NMR (200 MHz, CDCl₃): δ 8.23 (d, J = 7.4, 2H, ArH), 7.96 (m, 2H, ArH), 7.84 (bs, 2H, ArH), 7.80–7.78 (m, 3H, ArH), 7.67 (B part of AB system, J = 16.0, 1H), 7.60 (s, 1H, ArH), 7.29 (A part of AB system, J = 16.0, 1H), 7.23 (m, 2H, ArH), 7.11 (m, 2H, ArH), 6.99 (d, J = 7.4, 1H, ArH), 2.43 (s, –CH₃, 3H), 2.26 (s, –CH₃, 3H); ¹³C NMR (50 MHz, CDCl₃): δ 195.0, 189.0, 162.3, 154.8, 143.2, 142.1, 141.9, 141.1, 139.4, 138.8, 138.3, 133.8, 133.6, 131.4, 131.2, 131.0, 130.6, 129.6, 127.6, 127.1, 127.1, 123.4, 123.1, 121.7, 118.9, 115.3, 20.0, 19.8; ESI/MS m/z for C₃₂H₂₇N₂O₃ [M + H]⁺: 487 (100), 413 (2). Anal. calcd for C₃₂H₂₆N₂O₃: C, 78.99; H, 5.39; N, 5.76; found: C, 78.96; H, 5.37; N, 5.72%.

(E)-1-{3-Hydroxy-4-[(E)-{4-[(E)-3-m-tolylacryloyl]phenyl}diazenyl]phenyl}-3-m-tolylprop-2-en-1-one (5b): Dark red crystals; yield 0.53 g (65%); m.p. 101–103 °C; FTIR (KBr, cm^–1): 3170, 3067, 1654, 1584; ¹H NMR (200 MHz, CDCl₃): δ 8.04 (d, J = 7.4, 2H, ArH), 7.90 (m, 1H, ArH), 7.88 (d, J = 7.4, 2H, ArH), 7.75 (B part of AB system, J = 16.0, 1H), 7.59 (d, J = 7.6, 2H, ArH), 7.45 (m, 2H, ArH), 7.42 (A part of AB system, J = 16.0, 1H), 7.30 (m, 2H, ArH), 7.13 (m, 2H, ArH), 7.20 (m, 1H, ArH), 6.97 (s, 1H, ArH), 2.33 (s, –CH₃, 3H), 2.28 (s, –CH₃, 3H); ¹³C NMR (50 MHz, CDCl₃): δ 195.2, 189.0, 160.2, 154.4, 145.7, 144.8, 143.7, 139.1, 138.6, 138.5, 134.5, 134.2, 131.6, 129.5, 129.1, 128.8, 127.5, 125.8, 122.8, 121.4, 120.8, 118.6, 115.2, 21.8, 21.7; ESI/MS m/z for C₃₂H₂₇N₂O₃ [M + H]⁺: 487 (100), 413 (15). Anal. calcd for C₃₂H₂₆N₂O₃: C, 78.99; H, 5.39; N, 5.76; found: C, 78.98; H, 5.38; N, 5.73%.

(E)-1-{3-Hydroxy-4-[(E)-{4-[(E)-3-p-tolylacryloyl]phenyl}diazenyl]phenyl}-3-p-tolylprop-2-en-1-one (5c): Dark red crystals; yield 0.56 g (70%); m.p. 129–131 °C; FTIR (KBr, cm^–1): 3167, 3022, 1654, 1565; ¹H NMR (200 MHz, CDCl₃): δ 8.04 (d, J = 7.4, 2H, ArH), 7.92 (m, 1H, ArH), 7.88 (bs, 2H, ArH), 7.83 (bs, 1H, ArH), 7.75 (B part of AB system, J = 16.0, 1H), 7.52 (bs, 1H, ArH), 7.29 (A part of AB system, J = 16.0, 1H), 7.20 (m, 4H, ArH), 7.15 (m, 4H, ArH), 2.40 (s, –CH₃, 3H), 2.31 (s, –CH₃, 3H); ¹³C NMR (50 MHz, CDCl₃): δ 195.2, 190.0, 162.1, 154.8, 145.1, 144.1, 143.2, 142.2, 141.5, 141.4, 139.4, 132.5, 132.2, 130.4, 130.2, 129.7, 129.2, 127.7, 123.0, 121.5, 121.3, 118.7, 115.1, 21.3, 21.2; ESI/MS m/z for C₃₂H₂₇N₂O₃ [M + H]⁺: 487 (100), 449 (5). Anal. calcd for C₃₂H₂₆N₂O₃: C, 78.99; H, 5.39; N, 5.76; found: C, 78.96; H, 5.37; N, 5.72%.

(E)-3-(2-Fluorophenyl)-1-{4-[(E)-{4-[(E)-3-(2-fluorophenyl)acryloyl]-2-hydroxyphenyl}diazenyl]phenyl}prop-2-en-1-one (5d): Dark red crystals; yield 0.23 g (72%); m.p. 151–153 °C; FTIR (KBr, cm^–1): 3320, 3070, 1663, 1588; ¹H NMR (200 MHz, CDCl₃): δ 8.20 (d, J = 8.2, 2H, ArH), 8.13 (m, 2H, ArH), 7.99 (B part of AB system, J = 16.0, 1H), 7.91 (d, J = 9.1, 1H, ArH), 7.83–7.85 (m, 3H, ArH), 7.50 (A part of AB system, J = 16.0, 1H), 7.24–7.26 (m, 2H, ArH), 7.10 (d, J = 8.9, 4H, ArH), 6.97 (s, 1H, ArH); ¹³C NMR (50 MHz, CDCl₃): δ 192.1, 186.1, 161.5, 160.2, 156.2, 152.2, 140.4, 138.9, 136.3, 133.5, 132.1, 130.9, 130.7, 127.9, 127.1, 123.0, 121.9, 120.4, 120.1, 119.9, 119.3, 116.5, 114.3, 113.9, 112.8; ESI/MS m/z for C₃₀H₂₁F₂N₂O₃ [M + H]⁺: 495 (85), 413 (20). Anal. calcd for C₃₀H₂₀F₂N₂O₃: C, 72.87; H, 4.08; N, 5.67; found: C, 72.85; H, 4.11; N, 5.65%.

(E)-3-(3-Fluorophenyl)-1-{4-[(E)-{4-[(E)-3-(3-fluorophenyl)acryloyl]-2-hydroxyphenyl}diazenyl]phenyl}prop-2-en-1-one (5e): Dark red crystals; yield 0.22 g (68%); m.p. 85–87 °C; FTIR (KBr, cm^–1): 3239, 3066, 1657, 1580; ¹H NMR (200 MHz, CDCl₃): δ 8.28 (d, J = 8.0, 2H, ArH), 8.24 (d, J = 8.0, 2H, ArH), 8.08 (m, 1H, ArH), 8.06 (m, 1H, ArH), 7.99 (B part of AB system, J = 16.0, 1H), 7.78 (A part of AB system, J = 16.0, 1H), 7.66 (s, 2H, ArH), 7.51 (m, 2H, ArH), 7.40 (m, 2H, ArH), 7.13 (m, 2H, ArH), 6.97 (s, 1H, ArH); ¹³C NMR (50 MHz, CDCl₃): δ 195.8, 190.3, 166.3, 161.4, 159.1, 155.6, 143.7, 142.6, 142.3, 139.8, 138.6, 132.2, 126.3, 124.9, 124.0, 123.7, 121.8, 121.1, 118.8, 118.4, 116.0, 115.7; ESI/MS m/z for C₃₀H₂₁F₂N₂O₃ [M + H]⁺: 495 (100), 292 (99). Anal. calcd for C₃₀H₂₀F₂N₂O₃: C, 72.87; H, 4.08; N, 5.67; found: C, 72.85; H, 4.11; N, 5.64%.

(E)-3-(4-Fluorophenyl)-1-{4-[(E)-{4-[(E)-3-(4-fluorophenyl)acryloyl]-2-hydroxyphenyl}diazenyl]phenyl}prop-2-en-1-one (5f): Dark red crystals; yield 0.38 g (71%); m.p. 98–100 °C; FTIR (KBr, cm^–1): 3239, 1655, 1584; ¹H NMR (200 MHz, CDCl₃): δ 8.26 (d, J = 8.5, 2H, ArH), 8.02 (m, 2H, ArH), 7.91 (d, J = 9.0, 2H, ArH), 7.88 (B part of AB system, J = 15.4, 1H), 7.81 (d, J = 9.3, 2H, ArH), 7.72 (A part of AB system, J = 15.4, 1H), 7.45 (d, J = 8.1, 4H, ArH), 7.21 (s, 1H, ArH), 7.10 (d, J = 8.4, 2H, ArH); ¹³C NMR (50 MHz, CDCl₃): δ 194.4, 189.1, 166.8, 161.8, 158.2, 155.0, 143.4, 142.9, 142.6, 140.0, 139.0, 132.1, 131.3, 131.2, 130.6, 130.0, 128.5, 123.0, 122.1, 120.2, 116.5, 116.0, 115.1; ESI/MS m/z for C₃₀H₂₁F₂N₂O₃ [M + H]⁺: 495 (100), 413 (20). Anal. calcd for C₃₀H₂₀F₂N₂O₃: C, 72.87; H, 4.08; N, 5.67; found: C, 72.86; H, 4.10; N, 5.65%.

(E)-3-(2-Chlorophenyl)-1-{4-[(E)-{4-[(E)-3-(2-chlorophenyl)acryloyl]-2-hydroxyphenyl}diazenyl]phenyl}prop-2-en-1-one (5g): Dark red crystals; yield 0.23 g (71%); m.p. 99–101 °C; FTIR (KBr, cm^–1): 3177, 3032, 1654, 1584; ¹H NMR (200 MHz, CDCl₃): δ 8.25 (d, J = 7.6, 2H, ArH), 8.04 (m, 1H, ArH), 7.93 (m, 1H, ArH), 7.83 (d, J = 7.6, 2H, ArH), 7.77–7.75 (m, 2H, ArH), 7.72 (B part of AB system, J = 16.4, 1H), 7.43 (A part of AB system, J = 16.4, 1H), 7.51–7.46 (m, 4H, ArH), 7.39–7.35 (m, 2H, ArH), 6.99 (s, 1H, ArH); ¹³C NMR (50 MHz, CDCl₃): δ 194.4, 188.8, 161.1, 154.1, 142.7, 140.3, 140.2, 138.0, 134.9, 134.6, 132.3, 130.9, 130.7, 129.8, 129.6, 129.1, 127.0, 126.7, 123.8, 122.3, 120.6, 118.1, 114.7; ESI/MS m/z for C₃₀H₂₁Cl₂N₂O₃ [M + H]⁺: 527 (100), 302 (30). Anal. calcd for C₃₀H₂₀Cl₂N₂O₃: C, 68.32; H, 3.82; N, 5.31; found: C, 68.35; H, 3.80; N, 5.28%.

(E)-3-(3-Chlorophenyl)-1-{4-[(E)-{4-[(E)-3-(3-chlorophenyl)acryloyl]-2-hydroxyphenyl}diazenyl]phenyl}prop-2-en-1-one (5h): Dark red crystals; yield 0.25 g (77%); m.p. 122–124 °C; FTIR (KBr, cm^–1): 3173, 3042, 1653, 1584; ¹ H NMR (200 MHz, CDCl₃): δ 8.25 (d, J = 8.1, 2H, ArH), 8.07 (d, J = 8.0, 2H, ArH), 7.92 (d, J = 8.0, 1H, ArH), 7.83 (m, 1H, ArH), 7.75 (B part of AB system, J = 16.0, 1H), 7.60 (m, 2H, ArH), 7.51 (m, 2H, ArH), 7.48 (A part of AB system, J = 16.0, 1H), 7.43 (m, 2H, ArH), 7.40 (m, 2H, ArH), 7.20 (s, 1H, ArH); ¹³C NMR (50 MHz, CDCl₃): δ 194.2, 188.2, 162.2, 154.8, 143.1, 142.6, 141.7, 140.9, 137.3, 137.2, 135.1, 134.4, 130.7, 130.1, 130.0, 129.7, 128.1, 127.0, 123.5, 122.7, 120.7, 118.4, 114.9; ESI/MS m/z for C₃₀H₂₁Cl₂N₂O₃ [M + H]⁺: 527 (70), 449 (50). Anal. calcd for C₃₀H₂₀Cl₂N₂O₃: C, 68.32; H, 3.82; N, 5.31; found: C, 68.35; H, 3.80; N, 5.28%.

(E)-3-(2,4-Dichlorophenyl)-1-{4-[(E)-{4-[(E)-3-(2,4-dichlorophenyl)acryloyl]-2-hydroxyphenyl}diazenyl]phenyl}prop-2-en-1-one (5i): Dark red crystals; yield 0.23 g (72%); m.p. 136–138 °C; FTIR (KBr, cm^–1): 3217, 3065, 1656, 1582; ¹H NMR (200 MHz, CDCl₃): δ 8.24 (m, 2H, ArH), 8.05 (m, 2H, ArH), 7.99 (B part of AB system, J = 16.4, 1H), 7.92 (m, 1H, ArH), 7.81 (d, J = 8.0, 1H, ArH), 7.72 (A part of AB system, J = 16.4, 1H), 7.66 (m, 2H, ArH), 7.56 (m, 2H, ArH), 7.41 (m, 2H, ArH), 7.00 (s, 1H, ArH); ¹³C NMR (50 MHz, CDCl₃): δ 195.1, 188.9, 161.0, 154.2, 142.8, 140.4, 140.1, 138.1, 135.2, 135.0, 134.5, 132.4, 130.0, 129.2, 127.4, 127.1, 126.6, 123.9, 123.0, 120.6, 118.1, 114.6; ESI/MS m/z for C₃₀H₁₉Cl₄N₂O₃ [M + H]⁺: 597 (10), 483 (70). Anal. calcd for C₃₀H₁₈Cl₄N₂O₃: C, 60.43; H, 3.04; N, 4.70; found: C, 60.40; H, 3.02; N, 4.67%.

(E)-3-(2-Bromophenyl)-1-{4-[(E)-{4-[(E)-3-(2-bromophenyl)acryloyl]-2-hydroxyphenyl}diazenyl]phenyl}prop-2-en-1-one (5j): Dark red crystals; yield 0.27 g (82%); m.p. 99–101 °C; FTIR (KBr, cm^–1): 3218, 3063, 1652, 1574; ¹H NMR (200 MHz, CDCl₃): δ 8.26 (d, J = 8.6, 2H, ArH), 8.21 (d, J = 7.6, 2H, ArH), 8.04 (m, 1H, ArH), 7.98 (B part of AB system, J = 15.6, 1H), 7.94 (d, J = 8.9, 1H, ArH), 7.82 (A part of AB system, J = 15.6, 1H), 7.58 (m, 2H, ArH), 7.42 (m, 2H, ArH), 7.33 (m, 2H, ArH), 7.29 (s, 1H, ArH), 7.15 (m, 2H, ArH); ¹³C NMR (50 MHz, CDCl₃): δ 194.4, 188.8, 161.1, 154.1, 142.7, 140.7, 140.2, 138.2, 138.2, 134.1, 132.9, 132.8, 131.1, 130.8, 129.9, 129.1, 127.4, 127.3, 127.1, 125.3, 125.1, 124.1, 122.3, 120.7, 118.1, 114.6; ESI/MS m/z for C₃₀H₂₁Br₂N₂O₃ [M + H]⁺: 616 (100), 449 (20). Anal. calcd for C₃₀H₂₀Br₂N₂O₃: C, 58.47; H, 3.27; N, 4.55; found: C, 58.51; H, 3.22; N, 4.51%.

(E)-3-(3-Bromophenyl)-1-{4-[(E)-{4-[(E)-3-(3-bromophenyl)acryloyl]-2-hydroxyphenyl}diazenyl]phenyl}prop-2-en-1-one (5k): Dark red crystals; yield 0.23 g (70%); m.p. 113–115 °C; FTIR (KBr, cm^–1): 3241, 3059, 1656, 1591; ¹H NMR (200 MHz, CDCl₃): δ 8.25 (d, J = 8.6, 2H, ArH), 8.23 (m, 2H, ArH), 8.04 (m, 1H, ArH), 7.98 (m, 1H, ArH), 7.82 (B part of AB system, J = 15.6, 1H), 7.70 (m, 2H, ArH), 7.72 (A part of AB system, J = 15.6, 1H), 7.65 (m, 2H, ArH), 7.58 (m, 2H, ArH), 7.37 (m, 2H, ArH), 7.34 (s, 1H, ArH); ¹³C NMR (50 MHz, CDCl₃): δ 194.0, 188.3, 160.9, 153.9, 142.5, 140.3, 140.1, 138.1, 136.1, 132.6, 132.4, 130.0, 129.9, 128.9, 128.5, 126.7, 126.2, 122.2, 122.1, 120.1, 117.9, 114.4; ESI/MS m/z for C₃₀H₂₁Br₂N₂O₃ [M + H]⁺: 616 (50), 443 (30). Anal. calcd for C₃₀H₂₀Br₂N₂O₃: C, 58.47; H, 3.27; N, 4.55; found: C, 58.43; H, 3.25; N, 4.52%.

(E)-3-(4-Bromophenyl)-1-{4-[(E)-{4-[(E)-3-(4-bromophenyl)acryloyl]-2-hydroxyphenyl}diazenyl]phenyl}prop-2-en-1-one (5l): Dark red crystals; yield 0.23 g (71%); m.p. 124–126 °C; FTIR (KBr, cm^–1): 3312, 1655, 1584; ¹H NMR (200 MHz, CDCl₃): δ 8.22 (d, J = 8.6, 2H, ArH), 7.99 (B part of AB system, J = 15.6, 1H), 7.90 (d, J = 8.9, 1H, ArH), 7.87 (d, J = 8.5, 2H, ArH), 7.80 (d, J = 8.5, 1H, ArH), 7.73 (A part of AB system, J = 15.6, 1H), 7.68 (d, J = 8.1, 4H, ArH), 7.59 (d, J = 8.1, 4H, ArH), 7.30 (s, 1H, ArH); ¹³C NMR (50 MHz, CDCl₃): δ 194.8, 188.9, 161.2, 154.3, 143.3, 142.9, 141.4, 140.7, 138.5, 133.2, 131.8, 129.6, 129.3, 129.1, 128.2, 124.5, 124.3, 122.4, 121.9, 118.2, 114.8; ESI/MS m/z for C₃₀H₂₁Br₂N₂O₃ [M + H]⁺: 616 (70), 443 (10). Anal. calcd for C₃₀H₂₀Br₂N₂O₃: C, 58.47; H, 3.27; N, 4.55; found: C, 58.46; H, 3.29; N, 4.52%.