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3(2H)-Furanones promising candidates for synthesis of new fluorescent organic probes

Mohamed H A Soliman*a, Belal H M Husseinb, Nahla Abdel-Moatib & El-Sayed H M El-Tamanyb

a Chemistry Department, Faculty of Science, Suez University, Suez, Egypt

b Chemistry Department, Faculty of Science, Suez Canal University, Ismailia, Egypt E-mail: m.soliman1969@yahoo.com

Received 31 May 2016; accepted (revised) 3 January 2018

Several novel 3-arylidene-5-(4-methoxy-3-nitrophenyl)-2(3H)-furanones (2a-d) have been successfully prepared and used as precursors for building up of other new heterocyclic architectures such as pyrrolones (4a-c), (5) and unsaturated aroyl-hydrazides (7a-d). These aroyl-hydrazides have been subsequently converted into pyridazinone derivatives (8a-d) by refluxing in HCl/AcOH mixture. Eventually, benzoylation of the hydrazides (7a-c) with benzoyl chloride affords the corresponding N-benzoyl-3(2H)-pyridazinones (9a-c). The structures of all synthesized compounds have been established using elemental analysis and spectral methods. The photophysical (fluorescence and electronic absorption spectra) properties of newly synthesized compounds have also been investigated.

Keywords: Furanone derivatives, 2(3H)-pyrrolones, 3(2H)-pyridazinone, fluorescence and electronic spectra

Recently, much more attention has been paid to fluorescent probes because of their crucial role in investigation of biological systems such as in sensing the polarity of micro-environments of proteins, lipids and DNA as swell labelling1. The synthetic and biological importance 3(2H)-Furanones, butenolides, stems from the facile ring-opening of the β-lactone to give acyclic products, which undergo heterocyclization to give other synthetically and biologically useful architectures2. Therefore, the synthesis and properties of these compounds is interesting research area for many synthetic organic chemists and biologists.

Furthermore, the 3(2H)-furanone ring is essential subunit in many natural products isolated from diverse organisms like sponges, algae, animals, plants and insects3. This core unit plays a key role for inducing a wide range of pharmacological actions including antimicrobial4, cardiotonic5, analgesic6, anticancer7, antiviral HIV-18, and anti-inflammatory9. Moreover, 3(2H)-furanone moiety acts as the main core of several natural antitumor agents such as geiparvarin10, eremantholides11, jatrophone12, chinolone and ciliarin13. Despite a number of synthetic approaches utilized for preparation of 3(2H)-furanones were known14,15 however, they were in many cases limited to specific substitution patterns. So, the development of new alternative strategies for the preparation of these heterocyclic class and studying their reactivity is

therefore of considerable importance and continues to be a challenge. As well, the pharmacological efficacies of 3(2H)-furanones have been widely studied while to the best of our knowledge there are no reports about the fluorescence properties of 3(2H)-furanones.

Inspired by above literature outputs, we aimed herein to explore the absorption and fluorescence profiles of new 3-arylidene-5-(4-methoxy-3- nitrophenyl)-2(3H)-furanones and study their reactivity towards some nitrogen-donor nucleophiles, as well.

Experimental Section

The required 4-[4-methoxy-3-nitrophenyl]-4- oxobutanoic acid (1) was synthesized by condensing anisole with succinic anhydride in presence of anhydrous aluminium chloride under Friedel-Craft’s acylation reaction conditions16 with minor modification, followed by the nitration of the formed acid with a mixture of nitric and sulfuric acids.

Solvents were purified by distillation over an appropriate drying agent and were used immediately.

All other chemicals were commercially available and used without further purification. All melting points reported are uncorrected and determined by the open capillary tube method on a Büchi 510 melting point apparatus. Elemental analyses for C, H and N were performed with a Flash EA-1112 elemental analyzer.

IR spectra were recorded on a Perkin-Elmer 1430 ratio

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recording infrared spectrophotometer with CDS data in the range 400–4000 cm–1 as KBr discs. For signal intensities the following abbreviations were used: br (broad), sh (sharp), w (weak), m (medium), s (strong), vs (very strong). 1H NMR-spectra were obtained with a Bruker Avance DRX200 (200 MHz) spectrometer with calibration to the residual proton solvent signal in DMSO-d6 (2.52 ppm), CDCl3 (7.26 ppm) against TMS with δ = 0.00 ppm. Multiplicities of the signals were specified s (singlet), d (doublet), t (triplet), q (quartet) or m (multiplet). Mass spectra were measured on a GC- MSQP 1000EX Shimadzu. The Ultraviolet-Visible (UV-Vis) spectra of the new compounds in DMF (3×10−3 M) were scanned on a Shimadzu-1601PC UV-Vis automatic recording spectrophotometer with a 1 cm quartz cell for absorbance and spectral measurements. The emission spectra of the binary and ternary complexes were scanned on a JASCO-FP6300 spectrofluorometer with a 1 cm quartz cell.

General procedure for synthesis of 3-arylidene-5- (4-methoxy-3-nitrophenyl)-2(3H)-furanones, 3a-d A general procedure for the preparation of furanones as follow: A mixture of 4-[4-methoxy-3-nitrophenyl]-4- oxobutanoic acid (2) (2.53 g, 0.01 mol), aromatic aldehyde namely benzaldehyde, p-anisaldehyde, p-chlorobenzaldehyde or salicylaldehyde (0.01 mol), in acetic anhydride (5 mL) in the presence of catalytic amount of fused sodium acetate (0.82 g, 0.01 mol) was heated in a water bath for 4 h. Then the reaction mixture was allowed to cool to RT and the isolated solid was filtered, washed with ethanol and purified by recrystallization from the proper solvent to give (3a-d).

Samples of the isolated solids were characterized as follows.

3-(Benzylidene)-5-(4-methoxy-3-nitrophenyl)- 2(3H)-furanone, 3a: Obtained as yellow crystals from butanol in 75.71% yield, m.p. 240-242°C. IR (KBr): 1760 (s, sh, ν(C=O), furanone ring), 1520, 1347 (s, sh, ν(NO2)), 1125 (m, sh, ν(C-O-C), Ar-OMe), 1070 cm−1 (m, sh, ν (C-O-C), furanone ring); 1H NMR (200 MHz, CDCl3): δ 7.47-7.20 (m, 9H, ArH), 6.75 (s, 1H, =CHAr'), 3.98 (s, 3H, Ar-OCH3);

EI-MS: m/z Calcd for [C18H13NO5]+ 323.30. Obsd 323.0. Anal. Calcd for C18H13NO5: C, 66.8; H, 4.02;

N, 4.33. Found: C, 66.12; H, 3.97; N, 4.25%.

3-(4-Methoxybenzylidene)-5-(4-methoxy-3-nitrophenyl)- 2(3H)-furanone, 3b: Obtained as yellow crystals from butanol in 57.68% yield, m.p. 252-254°C. IR (KBr):

1764 (s, sh, ν(C=O), furanone ring), 1518, 1345 (s, sh, ν

(NO2)), 1121 (m, sh, ν(C-O-C), Ar-OMe), 1063 cm−1 (m, sh, ν(C-O-C), furanone ring); 1H NMR (200 MHz, CDCl3): δ 8.23-6.99 (m, 8H, ArH)), 6.91 (s, 1H, = CHAr'), 4.03 (s, 3H, OCH3), 3.90 (3H, s, OCH3); EI-MS: m/z Calcd for [C19H15NO6]+ 353.33.

Obsd 353.0. Anal. Calcd for C18H13NO5: C, 64.58; H, 4.24; N, 3.90. Found: C, 63.18; H, 4.21; N, 3.50%.

3-(4-Chlorobenzylidene)-5-(4-methoxy-3-nitrophenyl)- 2(3H)-furanone, 3c: Obtained as yellow crystals from acetic acid in 46.83% yield, m.p. 275-277°C. IR (KBr):

1774 (s, sh, ν(C=O), furanone ring), 1523, 1348 (s, sh, ν (NO2)), 1136 (m, sh, ν(C-O-C), Ar-OMe), 1076 cm−1 (m, sh, ν(C-O-C), furanone ring); 1H NMR (200 MHz, CDCl3): δ 7.57-7.23 (m, 8H, ArH), 6.88 (s, 1H,

=CHAr'), 4.05 (s, 3H, OCH3); EI-MS: m/z Calcd for [C18H12ClNO5]+ 357.75. Obsd 357.0. Anal. Calcd for C18H12ClNO5: C, 60.43; H, 3.38; N, 3.92. Found: C, 60.88; H, 3.41; N, 3.40%.

3-(2-Hydroxybenzylidene)-5-(4-methoxy-3-nitrophenyl)- 2(3H)-furanone, 3d: Obtained as yellow crystals from acetic acid in 46.72%yield, m.p. 250-252°C.IR (KBr):

1774 (s, sh, ν(C=O), furanone ring), 1523, 1348 (s, sh, ν (NO2)), 1136 (m, sh, ν(C-O-C), Ar-OMe), 1076 cm−1 (m, sh, ν(C-O-C), furanone ring); EI-MS: m/z Calcd for [C18H13NO6]+ 339.31. Obsd 339.0. Anal. Calcd for C18H12ClNO5: C, 63.72; H, 3.86; N, 4.13. Found: C, 63.69; H, 3.01; N, 3.91%.

Synthesis of 3-(2-oxo-5-(4-methoxy-3-nitrophenyl)- 2(3H)-furylidene)phthalide, 4

It was prepared by condensation of phthalic anhydride (1.48 g, 0.01 mol) with 4-[4-methoxy-3- nitrophenyl]-4-oxobutanoic acid (1) (2.53 g, 0.01 mol) in acetic anhydride (10 mL) in presence of catalytic amount of fused sodium acetate (0.82 g, 0.01 mol) under reflux conditions for 4 h. After cooling to RT, the solid isolated product was collected by filtration, washed with ethanol and purified by recrystallization from acetic acid to give brown crystals of 3 in 56.94% yield, m.p.

338-340°C.IR (KBr):1730 (s, ν(C=O), furanone) 1520, 1341 cm−1 (s, sh, ν (NO2)); 1H NMR (300 MHz, DMSO-d6, δ):

8.97-7.40 (m, 8H, ArH), 4.00 (s, 3H, OCH3); EI-MS:

m/z Calcd for [C19H11NO7]+ 365.30. Obsd 365.0. Anal.

Calcd for C18H12ClNO5: C, 62.47; H, 3.04; N, 3.83.

Found: C, 61.77; H, 3.33; N, 4.04%.

General procedure for Synthesis of 3-(arylidene)- 1-benzyl-5-(4-methoxy-3-nitrophenyl)-2(3H)- pyrrolone, 5a-c

A mixture of 3-(arylidene)-5-(4-methoxy-3- nitrophenyl)-2(3H)-furanone (3a-c) (0.01 mol), benzylamine (3.21 g, 0.03 mol) in ethanol (40 mL)

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was refluxed for 4 h. The solid product obtained after cooling was filtered off and purified by recrystallization from the proper solvent to give 5a-c.

3-(Benzylidene)-1-benzyl-5-(4-methoxy-3-nitrophenyl)- 2(3H)-pyrrolone, 5a: Obtained as yellow crystals from ethanol in 54.9% yield, m.p. 208-210°C. IR (KBr):1671 (s, ν(C=O) 1545, 1349 cm−1 (s, sh, ν(NO2)); 1H NMR (200 MHz, CDCl3): δ 7.80-7.02 (m, 15H, ArH), 3.98 (3H, s, OCH3), 3.93 (2H, s, CH2Ph); EI-MS: m/z Calcd for [C25H20N2O4]+ 412.45. Obsd 412.0. Anal. Calcd for C25H20N2O4: C, 72.8; H, 4.89; N, 6.79. Found: C, 72.45;

H, 4.61; N, 7.20%.

3-(4-Methoxybenzylidene)-1-benzyl-5-(4-methoxy- 3-nitrophenyl)-2(3H)-pyrrolone, 5b: Obtained as yellow crystals from butanol in 64.0% yield, m.p.

214-216°C. IR (KBr): 1691 (m, νC=O) 1523, 1348 cm−1 (s, sh, ν (NO2)); EI-MS: m/z Calcd for [C26H22N2O5]+ 442.48. Obsd 442.0. Anal. Calcd for C26H22N2O5: C, 70.58; H, 5.01; N, 6.33. Found: C, 70.73; H, 5.25; N, 6.56%.

3-(4-Chlorobenzylidene)-1-benzyl-5-(4-methoxy- 3-nitrophenyl)-2-(3H)-pyrrolone, 5c: Obtained as yellow crystals from butanol in 79.74% yield, m.p.

232-233°C.IR (KBr):1656 (m, ν(C=O) 1528, 1347 cm−1 (s, sh, ν (NO2)); 1H NMR (200 MHz, CDCl3): δ 7.90-7.03 (m, 14H, ArH), 3.99 (s, 3H, OCH3), 3.93 (s, 2H, CH2Ph); EI-MS: m/z Calcd for [C25H19ClN2O4]+ 446.89.

Obsd 446.0. Anal. Calcd for C25H19ClN2O4: C, 67.19; H, 4.29; N, 6.27. Found: C, 66.9; H, 3.79; N, 6.8%.

Synthesis of 3-(benzylidene)-1-hydroxyethyl-5-(4- methoxy-3-nitrophenyl)-2(3H)-pyrrolones, 6

A mixture of 3-(benzylidene)-5-(4-methoxy-3- nitrophenyl)-2(3H)-furanone (3a) (3.23 g, 0.01 mol) and ethanol amine (0.67 g, 0.011 mol) in ethanol (20 mL) was heated under reflux for 4 h. The solid product obtained after cooling was filtered off and crystallized from benzene to give (6). Orange crystals; Yield: 69.02 %. m.p.

189–191°C. IR (KBr): 3326 (broad, ν (OH)), 1676 (s, ν(C=O)), 1528, 1349 cm−1 (sh, ν (NO2)); 1H NMR (200 MHz, CDCl3): δ 8.03-7.07 (10H, m, ArH), 3.95 (3H, s, OCH3 of aryl group), 3.92-3.78 (1H, m, OH), 3.71–3.68 (2H, m, CH2OH), 3.27-3.20 (2H, m, NCH2); EI-MS: m/z Calcd for [C20H18N2O5]+ 366.38. Obsd 366. Anal. Calcd for C20H18N2O5: C, 65.57; H, 4.95; N, 7.65. Found: C, 65.65; H, 5.2; N, 7.10%.

Synthesis of 4-[4-chlorobenzylidene]-6-[4-methoxy- 3-nitrophenyl]-3-oxazinone, 7

To a solution of (2c) (3.58 g, 0.01 mol), in pyridine (40 mL), hydroxylamine hydrochloride (1.05 g, 0.015

mol) was added and the reaction mixture was refluxed for 4 hrs. The product obtained after cooling was filtered off and crystallized from butanol to give (6).

Yellow crystals; Yield: 75 %. m.p. 212–214°C. IR (KBr): 1741 (s, ν C=O), 1521, 1361 cm−1 (s, sh, ν (NO2)); 1H NMR (200 MHz, CDCl3): δ 8.15-6.99 (8H, m, ArH), 4.03 (3H, s, OCH3 of aryl group), 3.92 (2H, s, CH2Ar'); EI-MS: m/z Calcd for [C18H13ClN2O5]+ 372.76. Obsd 372. Anal. Calcd for C18H13ClN2O5: C, 58.00; H, 3.52; N, 7.52. Found: C, 57.83; H, 3.70; N, 7.35%.

Synthesis of 3-(4-methoxy-3-nitrobenzoyl)-2-(arylidene)- propionic acid hydrazide, 8a-d

To a solution of furanones (2a-d) (0.01 mol) in ethanol (20 mL), hydrazine hydrate (0.60 g, 0.012 mol) was added and the reaction mixture was stirred at RT for 5 h. Then, the reaction mixture was allowed to stand overnight, the isolated solid was filtered off, washed with cooled ethanol and crystallized from ethanol to give compounds (8a-d). Samples of isolated products were characterized as follow:

3-(4-Methoxy-3-nitrobenzoyl)-2-(benzylidene)- propionic acid hydrazide, 8a: Obtained as orange crystals in 49.13% yield, m.p. 118-120°C.IR (KBr):

3314 (w, ν NH2), 3199 (w, ν NH), 1689 (s, ν C=O benzoyl), 1654 (w, ν C=O amide), 1533, 1336 cm−1 (s, ν (NO2)). Anal. Calcd for C18H17N3O5: C, 60.84; H, 4.82; N, 11.82. Found: C, 60.8; H, 4.6; N, 11.60%.

3-(4-Methoxy-3-nitrobenzoyl)-2-(4-methoxybenzylidene)- propionic acid hydrazide, 8b: Obtained as orange crystals in 69.55% yield, m.p. 162-164°C. IR (KBr):3317 (m, ν NH2), 3196 (w, ν NH), 1688 (m, ν C=O, benzoyl), 1647(m, ν C=O, amide) 1527, 1345 cm−1 (s, ν (NO2));

1H NMR (300 MHz, DMSO-d6, δ): 7.87-6.82 (8H, m, ArH), 4.46 (2H, S, CH2), 3.91 (3H, s, OCH3 of aryl group), 3.82 (3H, s, OCH3 of arylidene group);

EI-MS: m/z Calcd for [C19H19N3O6-18]+ 367.38. Obsd 367. Anal. Calcd for C19H19N3O6: C, 59.22; H, 4.97;

N, 10.90. Found: C, 59.1; H, 4.6; N, 11.40%.

3-(4-Methoxy-3-nitrobenzoyl)-2-(4-chlorobenzylidene)- propionic acid hydrazide, 8c: Obtained as orange crystals in 37.03% yield, m.p. 216-218°C. IR (KBr):

3328 (w, ν NH2), 3198 (w, ν NH), 1691 (m, ν C=O, benzoyl), 1651 (m, ν C=O, amide) 1518, 1349 cm−1 (s, ν (NO2)); 1H NMR (300 MHz, DMSO-d6, δ): 7.86-6.87 (8H, m, ArH), 4.51 (2H, s, CH2), 3.91 (3H, s, OCH3 of aryl group); EI-MS: m/z Calcd for [C19H19ClN2O3-18]+ 340.80. Obsd 340. Anal. Calcd for C19H19ClN2O3: C, 63.60; H, 5.34; N, 7.8. Found: C, 63.41; H, 5.6; N, 7.93%.

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3-(4-Methoxy-3-nitrobenzoyl)-2-(2-hydroxybenzy lidene)-propionic acid hydrazide, 8d: Obtained as orange crystals in 36.69% yield, m.p. 192-194°C. IR (KBr):3438 (m, ν OH), 3332 (w, ν NH2), 3267 (w, ν NH), 1666 (m, ν C=O, benzoyl), 1632 (m, ν C=O, amide), 1536, 1354 cm−1 (s, sh, ν (NO2)); EI-MS: m/z Calcd for [C18H17N3O6-18]+ 353.33. Obsd 353. Anal.

Calcd for C18H17N3O6: C, 58.22; H, 4.61; N, 11.32.

Found: C, 58.7; H, 4.5; N, 11.40%.

Synthesis of 3(2H)-pyridazinones, 9a-d

A solution of 3-(4-methoxy-3-nitrobenzoyl)-2- (arylidene)-propionic acid hydrazides (8a-d) (1 g) in a mixture of HCl and acetic acid 1:1 v/v (20 mL) was heated under reflux for 4 h. The solid product obtained after cooling was filtered off and recrystallized from the proper solvent to give 4- (arylmethyl)-6-(4-methoxy-3-nitro phenyl)-3[2H]- pyridazinones (8a-d). Samples of isolated products were characterized as follow:

4-(Benzyl)-6-(4-methoxy-3-nitrophenyl)-3(2H)- pyridazinone, 9a: Obtained as orange crystals in 78.51 % yield, m.p. 249-250°C. IR (KBr):3433 (m, ν NH), 1662 (s, ν C=O), 1519, 1339 cm−1 (s, ν (NO2));

1H NMR (300 MHz, DMSO-d6, δ): 13.08 (1H, s, NH), 8.28-7.17 (9H, m, ArH), 3.97 (3H, s, OCH3 of aryl group) 3.87 (2H, s, CH2); EI-MS: m/z Calcd for [C18H15N3O4]+ 337.34. Obsd 337. Anal. Calcd for C18H15N3O4: C, 64.09; H, 4.48; N, 12.46. Found: C, 63.7; H, 4.5; N, 12.20%.

4-(4-Methoxybenzyl)-6-(4-methoxy-3-nitrophenyl)- 3(2H)-pyridazinone, 9b: Obtained as yellow crystals in 66.66 % yield, m.p. 278-280°C. IR (KBr):3145 (w, ν NH), 1653(s, ν C=O), 1515, 1341 cm−1 (s, ν(NO2));

EI-MS: m/z Calcd for [C19H17N3O5]+ 367.36. Obsd 367.

Anal. Calcd for C19H17N3O5: C, 62.12; H, 4.66; N, 11.44.

Found: C, 62.6; H, 5.01; N, 12.10%.

4-(4-Chlorobenzyl)-6-(4-methoxy-3-nitrophenyl)- 3(2H)-pyridazinone, 9c: Obtained as yellow crystals in 89.47% yield, m.p. 284-286°C.IR (KBr): 3225 (w, ν NH), 1656 (s, ν C=O), 1525, 1337 cm−1 (s, ν(NO2));

1H NMR (300 MHz, DMSO-d6, δ): 13.23 (1H, s, NH), 8.33-7.32 (8H, m, ArH), 3.96 (3H, s, OCH3 of aryl group), 3.83 (2H, s, CH2); EI-MS: m/z Calcd for [C18H14ClN3O4]+ 371.78. Obsd 371. Anal. Calcd for C18H14ClN3O4: C, 58.15; H, 3.8; N, 11.30. Found: C, 58.4; H, 3.7; N, 11.50%.

4-(2-Hydroxybenzyl)-6-(4-methoxy-3-nitrophe nyl)-3(2H)-pyridazinone, 9d: Obtained as yellow crystals in 74.0% yield, m.p274-275°C. IR (KBr):3219

(ν NH), 1655 (s, ν C=O) 1521, 1342 cm−1 (s, ν(NO2));

1H NMR (300 MHz, DMSO-d6, δ): 13.31 (H, s, NH), 9.62-6.71 (8H, m, ArH), 3.95 (3H, s, OCH3 of aryl group), 3.77 (2H, s, CH2); EI-MS: m/z Calcd for [C18H15N3O5]+ 353.34. Obsd 353. Anal. Calcd for C18H15N3O5: C, 61.19; H, 4.28; N, 11.89. Found: C, 60.7;

H, 3.9; N, 12.40%.

Reaction propionic acid hydrazides (8a-c) with benzoyl chloride

To a well stirred solution of the hydrazides (8a-c) (0.01 mol) in dry benzene (120 mL), benzoyl chloride (1.41 g, 0.01 mol) was added drop wise and the reaction mixture was refluxed for 4 h. The solid product obtained after cooling was filtered off, washed and crystallized from the proper solvent to give (10a-c). Samples of isolated products were characterized as follow:

2-Benzoyl-4-(benzyl)-6-(4-methoxy-3-nitrophenyl)- 3(2H)-pyridazinone, 10a: Obtained as orange crystals from butanol in 66.6% yield, m.p. 251-252°C. IR (KBr):

3237 (m, ν NH), 1710 (m, ν C=O, benzoyl), 1674 (s, ν C=O, amide) 1524, 1345 cm−1 (s, ν (NO2)); 1H NMR (200 MHz, CDCl3): δ 9.27 (1H, s, NH), 8.18-6.49 (15H, m, ArH), 3.97 (3H, s, OCH3 of aryl group). Anal. Calcd for C25H19N3O5: C, 68.02; H, 4.34; N, 9.52. Found: C, 68.3;

H, 4.2; N, 9.70%.

2-Benzoyl-4-(4-methoxybenzyl)-6-(4-methoxy-3- nitrophenyl)-3(2H)-pyridazinone, 10b: Obtained as orange crystals from acetone in 71.87% yield, m.p.

230-232°C. IR (KBr): 3243 (ν NH), 1685 (w, ν C=O, benzoyl), 1657 (m, ν C=O, amide) 1518, 1332 cm−1 (s, ν (NO2)); 1H NMR (200 MHz, CDCl3): δ 9.77 (1H, s, NH), 8.15-6.45 (14H, m, ArH), 3.96 (3H, s, OCH3 of aryl group), 3.88 (3H, s, OCH3 of arylidene group). Anal.

Calcd for C26H21N3O6: Calculated. (471.47): C, 66.24; H, 4.49; N, 8.91. Found: C, 66.9; H, 4.8; N, 9.70%.

2-Benzoyl-4-(4-chlorobenzyl)-6-(4-methoxy-3- nitrophenyl)-3(2H)-pyridazinone, 10c: Obtained as orange crystals from butanol in 63.66% yield, m.p 240-242°C. IR (KBr):3261 (m, ν NH), 1716 (w, ν C=O, benzoyl), 1664 (s, ν C=O, amide) 1521, 1341 cm−1 (s, ν (NO2)); 1H NMR (200 MHz, CDCl3): δ 9.16 (1H, s, NH), 8.39-6.43 (14H, m, ArH), 3.98 (3H, s, OCH3 of aryl group); EI-MS: m/z Calcd for [C25H18ClN3O5]+ 475.89.

Obsd 475. Anal. Calcd for C25H18ClN3O5 (475.89): C, 63.1; H, 3.81; N, 8.83. Found: C, 63.4; H, 3.8; N, 9.20%.

Results And Discussion

Chemistry

The key starting material, 4-[4-methoxy-3-nitrophenyl]- 4-oxobutanoic acid (1), was prepared by a well-known

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synthetic strategy employed to efficiently synthesize phenyloxobutanoic acids from aromatic hydrocarbon, anisole, in a 2-steps process: (i) acylation of anisole with succininc anhydride catalyzed by anhydrous aluminum chloride under Fridel Craft`s reaction conditions to yield our target γ-Ketoacid (1). (ii) Subsequent nitration of Ketoacid (1) with nitric acid/sulfuric acid mixture to yield nitrated phenyloxobutanoic acid (2). Thereafter, in situ simultaneous heterocyclization of nitrated product (2) coupled with Perkin condensation17 with aromatic aldehydes in acetic anhydride (Ac2O) using catalytic amount of fused sodium acetate (AcONa) afford 3- arylidene-5-(4-methoxy-3-nitrophenyl)-2(3H)-furanones (3a-d) (Scheme I).

In other route, heterocyclization of γ-ketoacid (1) using dehydrating catalyst mixture Ac2O/ AcONa in the presence of condensing agent, phthalic anhydride, afford the corresponding phthalide (3) (cf. Scheme I).

To explore the reactivity of 2(3H)-furanones (3a-d) as precursors for preparation of other important

heterocyclic architectures the following reactions were carried out (Scheme II); Initially, aminolysis of furanones (3a-c) with the benzylamine or ethanolamine as aminating agents in absolute ethanol under refluxing conditions led to furan ring-opening with the formation of the corresponding amides, which undergo in situ hetrocyclization into the corresponding pyrrolones (5a- c) and (6). On the other hand, aminolysis of furanone (3c) with hydroxyl amine hydrochloride in boiling pyridine afford the corresponding oxazinone (7).

Hydrazinolytic ring-opening of 2(3H)-furanones (3a-d) through their treatment with excess hydrazine hydrate in cold ethanol led tothe formation of the corresponding 3-(4-methoxy-3-nitrobenzoyl)-2-(arylmethylene)-

propionic acid hydrazides (8a-d) which readily underwent heterocyclization either upon the treatment with hydrochloric acid/acetic acid mixture or with benzoyl chloride in benzene to yield the corresponding 4-arylmethyl 3(2H)-pyridazinone (9a-d) or N-benzoyl- 3(2H)-pyridazinones (10a-c), respectively.

Scheme I — Schematic route for synthesis of 3-arylidene-5-(4-methoxy-3-nitrophenyl)-2(3H)-furanones 3a-d and compound 4

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Structural characterizations

Microanalytical data and mass spectrometry

All new compounds were prepared in convinced yields, gave satisfactory C, H, and N elemental analyses, which are consistent with the proposed formula for the parent salophens and their chelate complexes (see Experimental Section).

The electron impact mass spectra (EI-MS) of new compound are synonymous with their known stability as revealed by considerable contribution of a molecular ion peak [M]+•, a molecular mass signature for each compound in their mass spectra.

IR spectroscopic data

The following highlights can be concluded from the FTIR spectral data obtained for 2(3H)-furanones (3a-d): (i) The intense absorption bands in the region 1760–1776 cm−1 could be ascribed to the carbonyl group of the 2(3H)-furanone ring (C=O of

-unsaturated lactones). (ii) Two prominent peaks around 1525 and 1345 cm−1are characteristic for the nitro moiety. The IR spectrum of compound (6) showed a sharp band at 1676 cm−1 and a broad band in the region 3326 cm−1 which are corresponding to carbonyl group C=O and hydroxyl group OH, respectively. The infrared spectra of these compounds (8a-d) displayed bands in the region 3314–3438 cm−1 corresponding to (NH2) and bands in the region 3196–3267 cm−1 typical for (NH). Missing of the absorption bands assignable to the NH2 groups from the spectra of pyridazinones (9a-d) and (10a-d) demonstrate successful heterocyclization of propionic acid hydrazides (8a-d).

NMR studies

The common spectral peculiarities of the 1H NMR spectra for 2(3H)-furanones (3a-d) is represented in two characteristic singlets equivalent to one proton

Scheme II — Reactivity of 2(3H)-furanones 3a-d as precursors for preparation of other important heterocyclic architectures

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each around δ 6.0-6.7 and δ 7.0- 7.6 which could be assigned to the vinyl proton at C-4 of the furan ring and the olefinic hydrogen of the arylidene substituent.

Photophysical properties

Steady state UV–vis absorption spectroscopy

The UV spectra of 2(3H)-furanone derivatives mainly contain two absorption bands at about 260 and 410 nm which belong to the C=C-Ar and the conjugated carbonyl (O=C-C=C-Ar) fragments18. The electronic absorption spectra of compounds (3a-d) have been measured in N,N-dimethyl formamide (DMF) as represented in Figure 1.

The absorption spectra of (3a-d) show absorption peaks around 265 and 415 nm with high extinction coefficients due to -* transitions. The absorption properties of the studied compounds are listed in Table I.

It can be seen that the effect of substituents in 4-position of arylidene group (OCH3, Cl) will be significant (Figure 1). The replacement of the substituent in the para position of the benzyldine moiety is accompanied by a slight bathochromic shift of the absorption, which is caused by excess an electron density in the furan ring and involvement of the lone electron pair of oxygen in the common conjugation chain.

The absorption spectra of (5a-c) and (6) were displayed in Figure 2 and all compounds have absorption at about 305 nm. The compounds (5b) and (5c) have an

additional absorption band at about 405 nm due the effect of methoxy group and chlorine atom on the resonance structure. Compounds (5a) and (6) have similar absorption spectra indicating that the benzyl group has no significant effect on the electronic configuration of those compounds. There is no apparent conjugation between the pyrrole heterocycle and the benzyl group.

The absorption spectra of compounds (8a, 8b, 9c and 10b) have absorption at about 300 nm as shown in Figure 3. Compounds (9c and 10b) have an additional absorption band at about 415 nm due to the conjugated unsaturated carbonyl of pyradizinone ring.

Fluorescence spectra

The fluorescence spectra of compounds (3a-d) in DMF show the maximum emission band at about 500

Table I — Absorption and fluorescence spectral data for compounds 2-9

Compd Absorbance Fluorescence

max (nm) Log  max Ex (nm) max Em (nm)

3a 275

398

4.69 4.72

398 494

3b 271

414

4.52 4.64

414 508

3c 272

402

4.59 4.62

402 486

3d 270

400

4.36 4.39

400 489

5a 282 4.48 282

5b 303

414

4.52 3.74

414 472

5c 287

407

4.55 3.51

407 460

6 280 4.35 385 473

8a 301 4.00

8b 302 4.39 302 488

9c 305

420

3.98 3.96

420 543

595

10b 302

414

4.25 4.25

414 514

590

Figure 1 — Absorption spectra of compounds (3a-d) in DMF at RT

Figure 2 — Absorption spectra of compounds (5a-c) and (6) in DMF at RT

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nm with a shoulder at about 580 nm on excitation with wavelength photons at their maximum absorption (Figure 4). The positions of fluorescence maxima and the emission spectral shape depend only slightly on the nature and the positions of the substituents in the benzyldiene moiety. The fluorescence spectra of compounds (5b and 5c and 6) in DMF show the maximum emission band at 472, 460, and 473 nm, respectively.

The fluorescence spectra of (9c and 10b) exhibit two emission bands at about 543 and 595 nm as depicted in Figure 4. Compound (8b) has an emission band at 488 nm with high relative fluorescence intensity compared to the all investigated compounds. The fluorescence spectral data are listed in Table I. The difference in the photoluminescent property of these species can be attributed to the different structures and thus different intermolecular interactions. The photoluminescence

behavior of these 2(3H)furanone derivatives suggests that they may find potential application as light- emitting materials and this molecule can be suggested as probes for the study of biological compounds such as DNA, proteins and enzymes.

Conclusion

In this work, 3-arylidene-2(3H)-furanone derivatives were synthesized and used in the synthesis of a number of heterocyclic compounds such as 2(3H)-pyrrolone, oxazinone and 3(2H)-pyridazinone derivatives. The electronic absorption and fluorescence spectra of the synthesized compounds depend on the arylediene moiety.

References

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Figure 3 — The absorption spectra of compounds 8a, 8b, 9c, and 10b in DMF at RT

Figure 4 — The fluorescence spectra upon excitation at their maximum absorption

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