Synthesis, structure elucidation and plants growth promoting effects of novel quinolinyl chalcones

2.1 Synthesis and structure elucidation of the novel quinolinyl chalcones

Treatment of 3-acetyl-4-hydroxyquinolin-2(1H)-one (1) (Tomita, 1951) and/or 3-acetyl-2H-chromen-2-one (2) (Siddiqui et al., 2009; Sahu et al., 1996) with phenylhydrazine afforded the corresponding hydrazones 3 and 4 according to the literature methods (Kappe et al., 1995; Stadlbauer and Hojas, 2004; Chodankar et al., 1986). The synthesized hydrazones were reacted with Vilsmeier-Haack reagent (DMF-POCl₃) (Singh et al., 2005) furnishing the pyrazolo-4-carbaldehydes 5 and 6, respectively (Abdel-Megid et al., 2007; Laxmi et al., 2013).

The desired chalcones yielded efficiently under the well established conditions of the base-catalyzed Claisen– Schmidt reaction (Mogilaiah et al., 2010). Hence, condensation of equivalent quantities of pyrazole-4-carbaldehydes 5 and 6 with the proper 3-acetyl derivatives in the presence of piperidine as catalyst furnished the desirable chalcones 7 and 8 (Scheme 1). The assuming novel E-form enones 7 and 8 were identified from their spectral analysis. ¹H NMR spectrum displayed the vanishing of both pyrazolo-4-carbaldehydes 5 and 6 (—CHO) protons (Abdel-Megid et al., 2007; Laxmi et al., 2013) and instead the outcrop of ortho-coupled two doublets at δ range between 7.00 ppm and 8.00 ppm characteristic for both H_α and H_β. Coupling constant in the range among 15–16 Hz confirm the trans geometry at the vynilic protons of both 7 and 8 products. The structure of the suggested chalcones 7 and 8 were also supported on the basis of their mass (ESI) spectra which showed the promising peaks at m/z 538 [(M + Na)]⁺ and 518 [(M + H)]⁺, respectively.

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Scheme 1

Synthesis of the new chalcones 7 and 8.

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Common analytical methods were not able to distinguish between both 7 and 8 products due to their similar spectrum data. In a very elegant way, the structures elucidation was performed using homonuclear NOE experiments (NOESY 1D) as an excellent distinguishable tool. Using this approach has never been used according to our knowledge for structural determination of such chalcones. NOE experiment was carried out on the distinct OH groups at the quinolinone moiety of both products 7 and 8 (Fig. 1). Thus, irradiation of the OH singlet of one of the resulting chalcones that exhibits a high proton frequency (δ11.50 ppm), gives an adverse impact on one of the olefinic chalcone protons beside H-5 of the quinolinone ring indicating the proposed structure of chalcone 7 (Fig. 2), whilst running the same experiment on the other chalcone product gave a positive effect on only H-5 of the quinolinone ring as a strong support for the other suggested chalcone structure 8 (Fig. 3).

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Fig. 1

Confirmation of compound 7 and 8 structures utilizing NOE effect.

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Fig. 2

Confirmation of compound 7 structures utilizing NOE effect.

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Fig. 3

Confirmation of compound 8 structures utilizing NOE effect.

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2.2 Growth promoting effect of the novel quinolinyl chalcones

On an open field a beds of black cotton ground were arranged. Selective seeds of Hibiscus, Mint and Basil were selected accurately. The three types of seeds were separately planted and irrigated in the ready beds using the conventional way. From every bed crops were divided to two separate categories, category A (control category) and category B (treated category). Category (A) group were preserved without spraying, while that from category (B) were treated with the examined compounds. Category (B) were addressed with examined compounds before sowing to test promoting growth effects. Novel chalcones solutions were prepared individually in 1,4-dioxane (0.01 M) and were used for bed spraying thrice at fortnightly intervals (15, 30, 45, 60, 75 and 90 days).

Tests were performed to match the category (B) plants with that plants from category (A). Samples were taken at 15, 30, 45, 60, 75 and 90 days after sowing. Plants were accurately checked, and the number of functional leaves and heights of shoots were registered accurately. The percent of change in the shoot height and the No. of leaves was calculated according to the following equation: $$\%ofchange=\frac{\left(Finalparameter-Initialparameter\right)}{\mathit{Initial}parameter}\times 100$$

Results in Tables 1 and 2 show that all treated plants possess noteworthy growth in shoot in addition to a remarkable enhancement in the leaves numbers against the untreated samples. This enhancement of the growth in the treated plants is similar to (Kalambe et al., 2015) who reported the positive effect of substituted chalcones on some crop plants. The positive effect of substituted chalcones can be attributed to the fact that chalcones as flavonoids in plants have several roles such as suppression the inhibitors of auxin (the key growth hormones), pigments production, phytoalexins production, UV protectants, signal molecules in plantmicrobe interactions, antioxidants, and pollinator attractants or feeding deterrents (Rozmer and Perjési, 2016). These compounds have a critical role in the interaction of plants with their environment (Dao et al., 2011).

Interestingly chalcone 8 displayed more strong vegetative growth than chalcon7, as this appeared in the percent of the change in the chalcone 8 treated plants were obvious higher than that in chalcon 7 treated plants (Tables 1 and 2). This may be attributed to the far distance between the olefinic chalcone proton and the (—OH) group at the quinolinone moiety in chalcone 8 which permitted more stability in aqueous soil and more effective due to its free-soil mobility so be easy to be absorbed with plants (Salem et al., 2019).

3.1 General

Optimal automated melting point system was applied for melting points measurements and are not corrected. Purification of products was performed using thin layer chromatography with 0.2-mm silica gel F-254 (Merck) plates, visualization with ultra violet source (254 and 366 nm) exposure. (JASCO,V-670 UV–VIS–IR) double-beam spectrophotometer were applied for recording of IR spectra. Micro mass LC-ZMD spectrometric apparatus was used for detecting electrospray ionization (ESI) mass spectra. Varian Mercury VX-400apparatus was used for proton ¹H NMR spectral detection using(CD₃)₂SO as solvent and TMS as a reference. Perkin-Elmer 2400I was used for elemental microanalyses. 3-(4-Hydroxy-1-methyl-1,2-dihydro-2-oxoquinolin-3-yl)-1-phenyl-1H-pyrazole-4-carbaldehyd (5) and 3-(2-Oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde (6) have been synthesized according to the reported methods (Abdel-Megid et al., 2007; Laxmi et al., 2013).

3.2 Procedure for preparation of 3-(4-Hydroxy-1-methyl-1,2-dihydro-2-oxoquinolin-3-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde (5)

Phosphoryl chloride POCl₃ (30 mmol) was added up to DMF (30 mmol) with continuous stirring. The reaction content was left to cool down before adding the hydrazone3 (10 mmol) solution in DMF (10 ml). Stirring condition was maintained for 1 h at room temperature and then gradually raised to 70–80 °C for 4 h. The reaction content was decanted onto mashed ice and then cold potassium carbonate solution was used for neutralization. The precipitated product was separated by filtration before subjected to purification using flash-chromatography with ethyl acetate/petroleum ether as eluent (1:1, v/v). Finally crystallization was performed from ethanol to yield the product as yellow crystals; (40% yield); m.p 230–232 °C (Lit. 228–230 °C, Abdel-Megid et al., 2007).

3.3 Procedure for preparation of 3-(2-Oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazole-4- carbaldehyde (6)

POCl₃ (14 mmol) was added to cold DMF solution (14 mmol) at 0–5 °C. 3-[1-(phenyl-hydrazono)-ethyl]-chromen-2-one (4) (3.5 mmol) was added and the content was subjected to contentious stirring for 4 h at room temperature. Accomplishment of the reaction was adjusted by TLC. The reaction content was poured to ice before neutralization with 10% NaOH solution. The precipitate was filtered off, dried, and recrystallized from ethanol as yellow crystals; (60% yield); m.p 179–182 °C (Lit.180–185 °C, Laxmi et al., 2013).

3.4 Procedure for preparation of 4-hydroxy-1-methyl-3-(4-((2H-2-oxo-chromen-3-yl)prop-2-enoyl)-1-phenyl-1H-pyrazol-4-yl)quinolin-2(1H)-one (7)

Magnetically stirred solution of 5 (1 mmol) and 2 (1 mmol) in absolute ethanol (15 ml) was heated at 80 °C for 8 h with addition of catalytic piperidine drops. The resulted crystalline product that produced while hot was separated by filtration and purified by crystallized from ethanol to yield 7 as pale-yellow crystals, yield (0.412 g) 80%, m.p. > 300 °C. IR (KBr), (ν_max, cm⁻¹): 3430–3200 (br, OH), 3040 (C—H_arom.), 2930 (C—H_aliph.),1660–1630 (3C⚌O), 1590 (C⚌N), 1530 (C⚌C) cm⁻¹. ¹H NMR (400 MHz, DMSO): δ 3.65 (s, 3H, NCH₃),7.50 (d,1H,J 15.6 Hz, H_α), 7.26–8.15(m, 15H, Ar–H), 8.00(d, 1H, J 15.8 Hz, H_β),11.50 (s, 1H, OH). MS(ESI) m/z:MS (ESI) m/z 538 [(M + Na)⁺, 45%], 516 [(M + H)⁺, 20%], 515(1 0 0). Anal.calc. for C₃₁H₂₁N₃O₅ (515.52): C, 72.23; H, 4.11; N, 8.15. Found: C, 72.10; H, 3.95; N, 8.00%.

3.5 Procedure for preparation of 4-hydroxy-1-methyl-3-((2E)-3-(3-(2-oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazol-4-yl)acryloyl)quinolin-2(1H)-one (8)

Solution of 6 (1 mmol) and 1 (1 mmol) in absolute ethanol (15 ml) was heated under reflux for 8 h with addition of drops of catalytic piperidine. The resulted crystalline product that produced while hot was filtered and recrystallized using ethanol to yield 7 as pale yellow crystals, yield (0.386 g) 75%, m.p. > 300 °C. IR (KBr), (ν_max, cm⁻¹): 3410–3250 (br, OH), 3030 (C—H_arom.), 2910 (C—H_aliph.),1665–1635 (3C⚌O), 1580 (C⚌N), 1510 (C⚌C) cm⁻¹.¹H NMR (400 MHz, DMSO): δ 3.60 (s, 3H, NCH₃),7.40 (d,1H,J 15.6 Hz, H_α), 7.26–8.15(m, 15H, Ar–H), 7.95(d, 1H, J 15.8 Hz, H_β),11.60 (s, 1H, OH).MS(ESI) m/z :MS (ESI) m/z 538 [(M + Na)⁺, 25%], 516 [(M + H)⁺, 40%], 515(1 0 0). Anal.calc. for C₃₁H₂₁N₃O₅ (515.52): C, 72.23; H, 4.11; N, 8.15.Found: C, 71.95; H, 3.50; N, 7.90%.