Skip to main content
NCBI home page
ACS Omega logoLink to ACS Omega
. 2025 Feb 13;10(7):7317–7326. doi: 10.1021/acsomega.4c11066

Microwave-Assisted Synthesis of Near-Infrared Chalcone Dyes: a Systematic Approach

Younis Baqi 1,*, Ahmed Hussein Ismail 1
PMCID: PMC11865964  PMID: 40028138

Abstract

graphic file with name ao4c11066_0005.jpg

(E)-3-[4-(Dimethylamino)phenyl]-1-(2-hydroxyphenyl)prop-2-en-1-one is an organic dye with potential application in dye-sensitized solar cells. In order to fully investigate and characterize this molecule, many synthetic approaches were applied, including base and acid-catalyzed synthetic methodologies. NaOH, KOH, Ba(OH)2·8H2O, K2CO3, Et3N, SOCl2, HCl, HOAc, and Ac2O were utilized in different solvents and reaction conditions; however, all attempts failed to access the desired product in an efficient and productive way. A good success was achieved employing excess of piperidine, as base in refluxing ethanol. The reaction completed in 3 days; however, the product was obtained in 85% purity. In order to minimize the formation of side products, and taking in consideration a greener approach, such as shortening the extended reaction time and reducing excess production of organic wastes, the reaction was performed under controlled microwave reaction conditions. With greater success, the desired product was obtained in excellent isolated yield and high purity, in a shorter reaction time. This novel approach was then explored to investigate its scope and limitations to access other chalcone dyes.

1. Introduction

Solar energy is one of the most effective renewable and sustainable sources for electricity and energy.1,2 This electrical energy is obtained via harvesting solar radiation, which requires photosensitizers that are efficient in absorbing sunlight.3 Photosensitizers that are derived from natural organic dyes are particularly of interest due to their eco-friendliness, stability, and low toxicity compared to synthetic organic dyes.4,5

Chalcones (1,3-diaryl-2-propen-1-one) are a major class of naturally occurring secondary metabolites of plant origin and are structurally related to the flavonoid family of compounds. These metabolites are predominantly found in edible plants. Chalcones are key compounds in the biosynthesis of polyphenolic compounds that are well documented in the literature to possess many biological activities.6−11 Chalcone core comprises 15 carbon atoms incorporating an enone moiety, which is located between two aromatic rings, designated A and B (1, Figure 1). Chalcones have paramount applications in medicinal chemistry.12−20

Figure 1.

Figure 1

Open in a new tab

Chalcone skeleton and chemical structures of the selected bioactive chalcone derivatives.

A comparative pharmacological investigation of the chalcones has shown good antioxidant activity with low side effects, especially curcumin (2) and its structurally related molecules, such as yakuchinones A (3) and yakuchinones B (4)21−23 (Figure 1).

The chemical synthesis of chalcone is well established through the Claisen–Schmidt condensation reaction between acetophenone and benzaldehyde or their derivatives. The reaction can be catalyzed by a base, e.g., sodium hydroxide24, or an acid, e.g., acetic acid.25

(E)-3-[4-(Dimethylamino)phenyl]-1-(2-hydroxyphenyl)prop-2-en-1-one (7) is one of the most important chalcone dyes with potential application in dye-sensitized solar cells (DSSCs). In order to fully study and characterize this small molecule as well as to access closely related structure, especially incorporating an anchoring group, to be utilized in attaching these dyes on titanium dioxide (TiO2) surface for DSSC fabrication, more than 20 different procedures were employed. In the course of the reaction, the most challenging task was to consume all starting materials, especially aldehyde (4-(dimethylamino)benzaldehyde). Liquid chromatography coupled to mass spectrometer (LC-MS) identified the aldehyde as a frequent contaminate of the product (7) after purification. On the other hand, some of the published procedures lead to obtain two major products, visualized on the thin-layer chromatography (TLC), with the same mass of the desired product as analyzed by LC-MS. These two compounds are the stereoisomers (cis and trans) of the target compound. In an attempt to fully consume the starting materials, harsh reaction conditions were applied, such as elevated temperature for extended reaction time; however, such harsh reaction conditions led, in most cases, to decomposing of the starting materials and/or the desired product.

Six base- and four acid-catalyzed synthetic protocols were attempted, including sodium hydroxide (NaOH), potassium hydroxide (KOH), barium hydroxide octahydrate (Ba(OH)2·8H2O), potassium carbonate (K2CO3), triethylamine (Et3N), piperidine (C5H11N), thionyl chloride (SOCl2), hydrochloric acid (HCl), glacial acetic acid (HOAc), and acetic anhydride (Ac2O) in different solvents and reaction conditions. All of the attempted procedures failed to access the desired product (7) in an efficient and productive way. Except for the use of excess piperidine in refluxing ethanol for more than 3 days, the reaction produced the desired product (7) in very good isolated yield. However, chalcone 7 was found to be 85% pure. In order to reduce the excess piperidine used and to shorten the extended reaction time, the synthesis was performed under controlled microwave irradiation conditions using a dedicated microwave synthesizer. It has been well documented in the literature that the use of microwave heating dramatically reduces the reaction time and therefore resulting in increase in the yield and the efficiency of the reaction.26−31

Hereby, a systematic improvement access protocol for the synthesis of chalcone molecule (7) is described under conventional and controlled microwave irradiation technology in a green synthesis approach. Microwave irradiation improved the access to the target compound (7) in a single isomer with great success in reduction of the reaction time from 3 days to 30 min with excellent isolated yield and purity of 87 and 97%, respectively. Furthermore, this protocol was employed to access other chalcone derivatives that are structurally related to chalcone 7.

2. Results and Discussion

Twenty-six reaction protocols were employed for the synthesis of compound 7 starting from an equimolar concentration (1 mmol) of the starting materials 2′-hydroxy acetophenone (5) and of 4-aminodimethyl benzaldehyde (6) in 10 mL of solvent (Scheme 1).

Scheme 1. Claisen–Schmidt Synthesis of Chalcone 7.

Scheme 1

Open in a new tab

2.1. Synthesis of Chalcone 7 Using Sodium Hydroxide (NaOH)

Following, a published procedure using 2.5 equiv of 5% aqueous solution of sodium hydroxide under reflux condition at 90 °C was employed.32 The reaction was completed in 28 h, resulting in two new spots as visualized on TLC in 30% isolated yield (entry 1, Table 1). In the second attempt, ketone (6) was treated with 2 equiv. of sodium hydroxide (8.7%) to generate a carbanion ion before adding the aldehyde (5). The reaction mixture was refluxed at 90 °C for 96 h, and only 10% conversion was achieved (entry 2, Table 1).

Table 1. Sodium Hydroxide (NaOH) Catalyzed the Synthesis of Chalcone 7.

entry NaOH (%) equiv. solvent temperature (°C) time (h) %consumption (TLC/LC-MS) yield (%)
1 5 2.5 ethanol 90 28 100 30
2 8.7 2 ethanol/water (9:1) 90 96 10 –
3 40 5 ethanol 90 14 100 36
4 40 10 ethanol r.t. 50 100 52
5 40 10 ethanol 90 96 0 –
6 100 2.5 ethanol 90 10 100 82
7 100 5 methanol 70 120 100 33
Open in a new tab

In the next step, the amount of sodium hydroxide was increased to 5 equiv., using a higher concentration (40%) under reflux condition at 90 °C and as previously reported.33,34 Again, two spots were obtained in 36% yield after 14 h of refluxing (entry 3, Table 1). In an attempt to increase the yield of the reaction, the NaOH amount was further increased to 10 equiv. The isolated yield was improved to 52% stirring at r.t. over 50 h. However, the product showed two new spots on TLC (entry 4, Table 1). In order to investigate the effect of the reaction temperature, the mixture was refluxed at 90 °C, while 10 equiv. of sodium hydroxide (40%) was dropwise added. The reaction mixture was then kept refluxing for 96 h, and only the starting material spots were observed on TLC (entry 5, Table 1). This was probably due to the decomposition of the product or the initiation of a side competition reaction under the employed harsh reaction conditions. In the next attempt, 100% sodium hydroxide (2.5 equiv) in absolute ethanol was used, and the resulting mixture was then heated to reflux at 90 °C for 10 h, as previously reported.35 Also, two spots were obtained for the product as monitored by TLC despite the very good isolated yield (82%, entry 6, Table 1).

The final attempt was to change the solvent used and according to the following published procedure.36 In brief, the ketone (5) was dissolved in methanol followed by the addition of 5 equiv. of solid sodium hydroxide (100%). The resulting mixture was stirred for 30 min, followed by the addition of aldehyde (6), and the reaction mixture was refluxed at 70 °C for 120 h. Again, two spots for the product, in 33% yield, were observed (entry 7, Table 1).

2.2. Synthesis of Chalcone 7 Using KOH

KOH has been reported as a suitable base for the synthesis of chalcones.37,38 In an analogy to a published procedure, using 5 equiv. of 5% aqueous solution of KOH stirring at r.t. for 150 h was employed.37 The observed conversion was only 5% (entry 1, Table 2). A modified version of this protocol was applied to examine the effect of the following three parameters: quantity of KOH, temperature, and solvent. However, the maximum conversion achieved was only 50% of the starting materials despite the extended reaction times at ambient or refluxing conditions (entries 2 and 6, Table 2). In the next step, 2.5 “”equiv of 100% solid KOH was dissolved in methanol for 50 h and the refluxing condition was employed as previously reported.38 The best conversion of the starting materials achieved was only 50%, while the reaction reached equilibrium (entry 7, Table 2).

Table 2. KOH Catalyzed the Synthesis of Chalcone 7.

entry KOH (%) equiv. solvent temperature (°C) time (h) %consumption(TLC/LC-MS) yield (%)
1 5 5 ethanol r.t. 150 5 –
2 10 5 ethanol r.t. 150 20 –
3 40 5 ethanol r.t. 150 40 –
4 50 5 ethanol 90 100 50 –
5 100 2.5 ethanol 90 120 10 –
6 100 2.5 acetonitrile 90 120 5 –
7 100 2.5 methanol 70 50 50 –
Open in a new tab

2.3. Synthesis of Chalcone 7 Using Other Bases (Ba(OH)2·8H2O, K2CO3, and Et3N)

Using other bases, e.g., barium hydroxide hydrate (Ba(OH)2·8H2O), potassium carbonate (K2CO3), and triethylamine (Et3N) for the synthesis of chalcones has been reported in the literature.39,40 The starting materials were dissolved in methanol and barium hydroxide was added, and the mixture refluxed at 70 °C for 48 h.39 Only 40% conversion was achieved, and the reaction reached equilibrium (entry 1, Table 3). In the next step, potassium carbonate and triethylamine in different concentrations and solvents (acetonitrile, ethanol, and dioxane) under reflux conditions were employed.40 Despite the extended reaction times (26–120 h), the reaction achieved ca. 5% conversion (entries 2 and 4, Table 3).

Table 3. Synthesis of Chalcone 7 Using Other Selected Bases (Ba(OH)2·8H2O, K2CO3, and Et3N).

entry base equiv. solvent temperature (°C) time (h) %consumption (TLC/LC-MS) yield (%)
1 Ba(OH)2·8H2O 1 methanol 70 48 40 –
2 K2CO3 5 acetonitrile 90 100 0 –
3 K2CO3 2.5 ethanol 90 120 5 –
4 Et3N 2.2 dioxane 110 26 0 –
Open in a new tab

2.4. Synthesis of Chalcone 7 Under Acidic Reaction Conditions (SOCl2, HCl, HOAc, and Ac2O)

The acid-catalyzed synthesis of chalcones has been previously reported.41−43 In this reaction the starting materials were dissolved in absolute ethanol and allowed to stir at r.t. followed by the dropwise addition of thionyl chloride, and the resulting mixture was kept stirring and followed over 55 h; no conversion was observed (entry 1, Table 4). In the second attempt, the temperature was raised under SOCl2/EtOH refluxing conditions for 18 h; again, no progress was observed (entry 2, Table 4).41 The effect of thionyl chloride equivalency was examined, and the reaction was carried using 4.5 equiv of SOCl2 stirring at r.t. for 200 h; only starting materials were detected (entry 3, Table 4).42 In the next step, concentrated hydrochloric acid in glacial acetic acid as solvent was employed;43 stirring at r.t. for 24 h did not alter the reaction; and no conversion was observed (entry 4, Table 4). In the final attempt, the reaction was carried out in refluxing glacial acetic acid or acetic anhydride at 120 °C for 24 h; starting materials were persisted; and no conversion was observed (entry 5 and 6, Table 4, respectively).

Table 4. Acid-Catalyzed Synthesis of Chalcone 7.

entry acid equiv. solvent temperature (°C) time (h) %conversion (TLC/LC-MS) yield (%)
1 SOCl2 1.5 Ethanol r.t. 55 0 –
2 SOCl2 1.5 Ethanol 90 18 0 –
3 SOCl2 4.5 Ethanol r.t. 200 0 –
4 HCl conc. 12.5 HOAc r.t. 48 0 –
5 HOAc 87.5 – 120 24 0 –
6 Ac2O 53 – 120 24 0 –
Open in a new tab

2.5. Synthesis of Chalcone 7 Using Piperidine under Conventional and Microwave Heating

Starting materials were dissolved in ethanol and subjected to reflux at 90 °C, followed by the addition of excess (10 equiv) of piperidine, and the reaction mixture was kept refluxing until all starting materials were consumed. The reaction achieved in 74 h resulted in two isomer compounds as determined by LC-MS. The desired product was obtained in 81% yield and found to be 85% pure in the LC-MS analysis (entry 1, Table 5).44

Table 5. Conventional and Microwave Heating for the Synthesis of Chalcone 7.

entry piperidine equiv. reaction condition solvent temperature (°C) time (h) yield (%) purity (%) by LC-MS
1 10 conventional ethanol 90 74 81 85
2 2 microwave ethanol 100 0.5 87 97
Open in a new tab

Taking in consideration a green approach, a reduction in the extended reaction time, and minimizing the excess usage of piperidine (10 equiv), hence lesser chemical waste production, the reaction was redesigned to be conducted under microwave irradiation using fivefold less of piperidine (2 equiv). In brief, 2 equiv of piperidine was added to the solution of 2′-hydroxy acetophenone (5) and 4-aminodimethyl benzaldehyde (6) dissolved in ethanol (7 mL) in a microwave reaction vessel (10 mL). The resulting mixture was then irradiated in a CEM microwave synthesizer with 120 W, at 100 °C, and internal pressure up to 10 bar for 30 min. After completion of the reaction, the reaction vessel was cooled down to r.t. and then dark red crystals started to precipitate; see Figure 2 and Video S1 (Supporting Information). The microwave reaction vessel was allowed to settle for 60 min, and dark red crystals (Figure 2C) were collected via suction filtration and washed with ice-cold water/ethanol (1:1) (3 × 2 mL). The resulting crystals were air-dried to yield 87% of shiny dark red crystals. 4-(N,N-dimethylamino)-2′-hydroxychalcone (7) obtained excellent purity (97%) (entry 2, Table 5). The employed chemical analyses, e.g., TLC, LC-MS, NMR and X-ray, all confirmed that chalcone 7 was present in a single product in E configuration; see Supporting Materials for the detailed analyses.

Figure 2.

Figure 2

Open in a new tab

Microwave reaction vessel (10 mL) contain starting materials (5 and 6), piperidine, and ethanol; (A) before microwave irradiation, (B) after microwave irradiation, and (C) after microwave irradiation and cooling to r.t; for crystal formation, see video S1 in the Supporting Information.

In an attempt to explore the reaction, scope, and limitations, several acetophenones and aldehyde derivatives are explored in Table 6. The replacement of the N,N-dimethyl by the N,N-diethyl group in the 4-position of the benzaldehyde side and keeping the hydroxy group in the 2′-position of the acetophenone successfully produced the desired product, compound 8. The replacement of these electron-donating groups, N,N-dimethyl and N,N-diethyl, by hydrogen, methoxy, or nitro group resulted in mainly decomposition of the starting materials as seen in many spots on TLC, compounds 18–20. In the following step, we kept the electron-donating group (N,N-dimethyl or N,N-diethyl) in the 4-position of the aldehyde moiety while examining the acetophenone side of the chalcone. Different substituents, such as methyl, and fluoro at the 5′-position and fluoro at the 4′-position besides the presence of a hydroxy group in the 2′-position were found to be tolerated, compounds 9–13. Introducing an extra hydroxy group in the 5′-position was not tolerated, compounds 21 and 22. While the removal of the hydroxy group from the 2′-position resulted in a low yield, compound 14 is shown in Table 6.

Table 6. Microwave-Assisted Claisen–Schmidt Synthesis of Chalcone Derivatives.

2.5.

compds R1 R2 n color yield %
8 2-OH N(C2H5)2 1 dark brown 64
9 5-F-2-OH N(CH3)2 1 brown 79
10 4-F-2-OH N(CH3)2 1 orange 62
11 2-OH-5-CH3 N(C2H5)2 1 red 48
12 5-F-2-OH N(C2H5)2 1 red 64
13 4-F-2-OH N(C2H5)2 1 red 48
14 H N(CH3)2 1 red 32
15 2-OH N(CH3)2 2 dark red 56
16 4-Br N(CH3)2 1 orange 65
17 4-Br N(C2H5)2 1 orange 60
18 2-OH H 1 – –
19 2-OH OCH3 1 – –
20 2-OH NO2 1 – –
21 2,5-di–OH N(CH3)2 1 – –
22 2,5-di–OH N(C2H5)2 1 – –
Open in a new tab

3. Materials and Methods

3.1. General

All starting materials and solvents were purchased from commercial suppliers and were used as received. TLC was performed using TLC aluminum sheets with silica gel 60 F254. Colored compounds were visible at daylight; other compounds were visualized under UV light (254 nm). 1H- and 13C NMR data were collected on a Bruker Avance 500 MHz (1H) or 126 MHz (13C), respectively. DMSO-d6 was used as solvent. Chemical shifts were reported in parts per million (ppm) relative to the deuterated solvent, that is, DMSO, δ 1H: 2.49 ppm and 13C: 39.7 ppm; coupling constants J were given in Hertz; and spin multiplicities were given as s (singlet), d (doublet), t (triplet), and m (multiplet). The purities of isolated products were determined by ESI mass spectra obtained on an LC-MS instrument (Applied Biosystems API 2000 LC-MS, HPLC Agilent 1100) as previously described.45 For microwave reactions, a CEM Focused Microwave Synthesis-type Discover apparatus was used. Melting points were determined on an electro thermal capillary apparatus and were uncorrected.

3.2. Methods and Protocols

3.2.1. Synthesis Using Sodium Hydroxide (NaOH) as Catalyst32−36

3.2.1.1. Sodium Hydroxide (5%, 2.5 equiv) in Refluxing Ethanol

The aqueous solution of NaOH (5%, 2.5 mmol) was gradually added to the solution prepared from 2′-hydroxy acetophenone (1 mmol) dissolved in absolute ethanol (10 mL) and allowed to stir at r.t. for 30 min. Followed by the addition of 4-aminodimethyl benzaldehyde (1 mmol), the resulting mixture was refluxed at 90 °C for 28 h.32 The reaction was worked up by cooling down to r.t., then treated with ice-cold water and neutralized by diluted HCl (0.5 M), and the red precipitate was filtered off, washed with cold water (3 × 10 mL), air-dried, and collected in 30% yield composed of two isomers (cis and trans) of the products in a 6:4 ratio.

3.2.1.2. Sodium Hydroxide (40%, 5 equiv) in Ethanol at Room Temperature33,34

The aqueous solution of NaOH (8.7%, 2 mmol) was gradually added to solution of 2′-hydroxy acetophenone (1 mmol) dissolved in a mixture of ethanol/water (9:1). Followed by the addition of 4-aminodimethyl benzaldehyde (1 mmol), the mixture was refluxed at 90 °C for 96 h, resulting in 10% conversion of the starting materials.

3.2.1.3. Sodium Hydroxide (40%, 5 equiv) in Ethanol at Room Temperature33,34

The aqueous solution of NaOH (40%, 5 mmol) was dropwise added to a solution of 2′-hydroxy acetophenone (1 mmol) dissolved in absolute ethanol (10 mL); the resulting solution was stirred for 30 min, followed by the addition of 4-aminodimethyl benzaldehyde (1 mmol); and the resulting mixture was stirred at r.t. for 50 h. The reaction mixture was quenched by pouring it on crushed ice and then neutralized by diluted HCl [0.5 M]. The red precipitate was collected by suction filtration washed with cold water (3 × 10 mL) and air-dried resulting in a red powder product (52% yield) composed of two isomers (cis and trans) of the products in a 6:4 ratio.

3.2.1.4. Sodium Hydroxide (40%, 5 equiv) in Refluxing Ethanol33,34

The aqueous solution of NaOH (40%, 5 mmol) was dropwise added to a solution of 2′-hydroxy acetophenone (1 mmol) dissolved in absolute ethanol (10 mL); the resulting mixture was then stirred for 30 min, followed by the addition of 4-aminodimethyl benzaldehyde (1 mmol); and the mixture was heated to reflux at 90 °C for 14 h. Upon the reaction completed, monitored by TLC, the mixture was cooled down to r.t., treated with ice-cold water, and then neutralized by diluted HCl [0.5 M], and the resulting red precipitate was filtered, washed with cold water (3 × 10 mL), and air-dried. The red powder was obtained in 36% yield composed of two isomers (cis and trans) of the products in a 6:4 ratio.

3.2.1.5. Sodium Hydroxide (40%, 10 equiv) in Refluxing Ethanol33,34

The aqueous solution of NaOH (40%, 10 mmol) was dropwise added to 2′-hydroxy acetophenone (1 mmol) dissolved in absolute ethanol (10 mL), and the resulting solution was stirred for 30 min followed by the addition of 4-aminodimethyl benzaldehyde (1 mmol), and the resulting mixture was refluxed at 90 °C. Following the reaction over 96 h, resulting in no conversion of the starting materials, the reaction mixture was discarded.

3.2.1.6. Sodium Hydroxide (100%, 2.5 equiv) in Refluxing Ethanol35

Solid sodium hydroxide (2.5 mmol) was added to a solution of 2′-hydroxy acetophenone (1 mmol) in ethanol (10 mL), and the resulting mixture was stirred at r.t. for 30 min followed by the addition of 4-aminodimethyl benzaldehyde (1 mmol), and the reaction mixture was heated to reflux at 90 °C for 10 h. The reaction was cooled down to r.t., poured on crushed ice, and neutralized by diluted HCl [0.5 M]; the resulting red precipitate was filtered, washed with cold water (3 × 10 mL), and air-dried. The collected red powder had an 82% yield composed of two isomers (cis and trans) of the products in a 6:4 ratio.

3.2.1.7. Sodium Hydroxide (100%, 5 equiv) in Refluxing Methanol36

Solid sodium hydroxide (5 mmol) was added to a solution of 2′-hydroxy acetophenone (1 mmol) in methanol (10 mL), and the resulting mixture was allowed to stir at r.t. for 30 min. Followed by the addition of 4-aminodimethyl benzaldehyde (1 mmol), the mixture was refluxed at 70 °C for 120 h. The reaction was quenched by pouring it on crushed ice and neutralized with diluted HCl [0.5 M]. The red precipitate was filtered off by suction filtration, washed with cold water (3 × 10 mL), and air-dried to yield 33% of two isomers (cis and trans) of the products in a 6:4 ratio.

3.2.2. Synthesis Using KOH as Catalyst37,38

3.2.2.1. KOH (5%, 5 equiv) in Ethanol at Room Temperature

The aqueous solution of KOH (5%, 5 mmol) was gradually added to a solution of 2′-hydroxy acetophenone (1 mmol) dissolved in absolute ethanol (10 mL), and the resulting mixture was stirred for 30 min at r.t. followed by the addition of 4-aminodimethyl benzaldehyde (1 mmol) and the resulting mixture was heated to reflux at 90 °C for 150 h. Despite the extended reaction time, the conversion of the starting materials was 5% and the reaction mixture was then discarded.

3.2.2.2. KOH (10%, 5 equiv) in Ethanol at Room Temperature

The aqueous solution of KOH (10%, 5 mmol) was gradually added to the mixture of 2′-hydroxy acetophenone (1 mmol) dissolved in absolute ethanol (10 mL), and the reaction mixture was allowed to stir for 30 min at r.t. Followed by the addition of 4-aminodimethyl benzaldehyde, the reaction was kept stirring at r.t. for 150 h. It resulted in 20% conversion of the starting materials, and the reaction mixture was discarded.

3.2.2.3. KOH (40%, 5 equiv) in Ethanol at Room Temperature

The aqueous solution of KOH (40%, 5 mmol) was added to the solution of 2′-hydroxy acetophenone (1 mmol) in absolute ethanol (10 mL), and the reaction mixture was allowed to stir for 30 min at r.t. followed by the addition of 4-aminodimethyl benzaldehyde (1 mmol) and the reaction mixture was kept stirring at r.t. for 150 h. Resulting in 40% conversion of the starting materials, the reaction mixture was discarded.

3.2.2.4. KOH (50%, 5 equiv) in Refluxing Ethanol

The aqueous solution of KOH (50%, 5 mmol) was added to the solution of 2′-hydroxy acetophenone (1 mmol) in absolute ethanol (10 mL) and allowed to stir at r.t. for 30 min. Followed by the addition of 4-aminodimethyl benzaldehyde (1 mmol), the reaction mixture was refluxed at 90 °C for 100 h. Despite the extended reaction time, the consumption of the starting materials was only 50%, and the reaction mixture was discarded.

3.2.2.5. KOH (100%, 2.5 equiv) in Refluxing Ethanol

Solid KOH (2.5 mmol) was portion-wise added to the solution of 2′-hydroxy acetophenone (1 mmol) in absolute ethanol (10 mL), and the resulting mixture was allowed to stir at r.t. for 30 min. Followed by the addition of 4-aminodimethyl benzaldehyde (1 mmol), the reaction mixture was then heated to reflux at 90 °C for 120 h, resulting in 10% conversion of the starting materials, and the reaction mixture was discarded.

3.2.2.6. KOH (100%, 2.5 equiv) in Refluxing Acetonitrile

Solid KOH (2.5 mmol) was added to the solution composed of an equimolar concentration (1 mmol) of 2′-hydroxy acetophenone and 4-aminodimethyl benzaldehyde dissolved in acetonitrile (10 mL). The reaction mixture was then refluxed at 90 °C for 120 h, resulting in 5% conversion of the starting materials, and the reaction mixture was discarded.

3.2.2.7. KOH (100%, 2.5 equiv) in Refluxing Methanol

Solid KOH (5 mmol) was added to the solution of 2′-hydroxy acetophenone (1 mmol) in methanol (10 mL) and allowed to stir at r.t. for 30 min. Followed by the addition of 4-aminodimethyl benzaldehyde (1 mmol), the resulting mixture was heated to reflux at 70 °C for 120 h. Despite the extended reaction time, the consumption of the starting materials was only 50%, and the reaction mixture was discarded.

3.2.3. Synthesis Using Other Bases (Ba(OH)2·8H2O, K2CO3, and Et3N) as Catalyst39,40

3.2.3.1. Barium Hydroxide Octahydrate (100%, 1 equiv) in Refluxing Methanol

Barium hydroxide octahydrate (1 mmol) was added to a solution composed of 2′-hydroxy acetophenone (1 mmol) and 4-aminodimethyl benzaldehyde (1 mmol) in methanol (10 mL), then the reaction mixture was refluxed at 70 °C for 48 h, resulting in 40% conversion of the starting materials, and the reaction mixture was discarded.

3.2.3.2. Potassium Carbonate (100%, 5 equiv) in Refluxing Acetonitrile

Potassium carbonate (5 mmol) was added to the solution of 2′-hydroxy acetophenone (1 mmol) and 4-aminodimethyl benzaldehyde (1 mmol) in acetonitrile (10 mL), and the resulting mixture was refluxed at 90 °C for 100 h; no conversion in the starting materials was observed, and the reaction mixture was discarded.

3.2.3.3. Potassium Carbonate (100%, 2.5 equiv) in Refluxing Ethanol

Potassium carbonate (2.5 mmol) was added to a solution of 2′-hydroxy acetophenone (1 mmol) and 4-aminodimethyl benzaldehyde (1 mmol) dissolved in absolute ethanol (10 mL). The resulting mixture was heated to reflux at 90 °C for 100 h, resulting in 5% conversion of the starting materials, and the reaction mixture was discarded.

3.2.3.4. Triethylamine (100%, 2.2 equiv) in Refluxing 1,4-Dioxane

Triethylamine (2.2 mmol) was dropwise added to a solution of 2′-hydroxy acetophenone (1 mmol) and 4-aminodimethyl benzaldehyde (1 mmol) dissolved in 1,4-dioxane (10 mL); the reaction mixture was heated to reflux at 110 °C for 26 h, no conversion in the starting materials was observed, and the reaction mixture was discarded.

3.2.4. Synthesis Under Acidic Reaction Conditions (SOCl2, HCl, HOAc, and Ac2O)41−43

3.2.4.1. Thionyl Chloride (100%, 1.5 equiv) in Ethanol at Room Temperature

Thionyl chloride (1.5 mmol) was dropwise added to a solution composed of equimolar concentration (1 mmol) of 2′-hydroxy acetophenone and 4-aminodimethyl benzaldehyde dissolved in absolute ethanol (10 mL); the resulting mixture was let to stir at r.t. for 55 h. No conversion in the starting materials was observed, and the reaction mixture was discarded.

3.2.4.2. Thionyl Chloride (100%, 1.5 equiv) in Refluxing Ethanol

Thionyl chloride (1.5 mmol) was dropwise added to an equimolar concentration (1 mmol) of 2′-hydroxy acetophenone and 4-aminodimethyl benzaldehyde dissolved in absolute ethanol (10 mL); the resulting mixture was refluxed at 90 °C for 18 h. No conversion in the starting materials was observed, and the reaction mixture was discarded.

3.2.4.3. Thionyl Chloride (100%, 4.5 equiv) in Ethanol at Room Temperature

Thionyl chloride (4.5 mmol) was gradually added to an equimolar concentration (1 mmol) of 2′-hydroxy acetophenone and 4-aminodimethyl benzaldehyde dissolved in absolute ethanol (10 mL); the resulting mixture was allowed to stir at rt for 200 h. No conversion in the starting materials was observed, and the reaction mixture was discarded.

3.2.4.4. Hydrochloric Acid (37%, 12.5 equiv) in Glacial Acetic Acid at Room Temperature

Hydrochloric acid (37%, 12.5 mmol) was dropwise added to an equimolar concentration (1 mmol) of 2′-hydroxy acetophenone and 4-aminodimethyl benzaldehyde dissolved in glacial acetic acid (5 mL), and the resulting mixture was allowed to stir at rt for 48 h; no conversion in the starting materials was observed, and the reaction mixture was discarded.

3.2.4.5. Glacial Acetic Acid (100%, 87.5 equiv) as Catalyst and Refluxing Solvent

An equimolar concentration (1 mmol) mixture of 2′-hydroxy acetophenone and 4-aminodimethyl benzaldehyde (1 mmol) was dissolved in glacial acetic acid (5 mL). The resulting mixture was then heated to reflux at 120 °C for 24 h; no conversion in the starting materials was observed, and the reaction mixture was discarded.

3.2.4.6. Acetic Anhydride (100%, 53 equiv) as Catalyst and Refluxing Solvent

A mixture of 2′-hydroxy acetophenone (1 mmol) and 4-aminodimethyl benzaldehyde (1 mmol) dissolved in acetic anhydride (5 mL), and the resulting mixture was refluxed at 120 °C for 24 h; no conversion in the starting materials was observed, and the reaction mixture was discarded.

3.2.5. Synthesis Using Piperidine ((CH2)5NH) under Conventional and Microwave Heating

3.2.5.1. Piperidine (100%, 10 equiv) in Refluxing Ethanol44

Piperidine (10 mmol) was gradually added to a solution of 2′-hydroxy acetophenone (1 mmol) and 4-aminodimethyl benzaldehyde (1 mmol) dissolved in absolute ethanol (10 mL). The resulting mixture was refluxed at 90 °C for 74 h. After consumption of all starting materials, the solvent was evaporated under vacuum and the remaining materials were treated with ice-cold water; the resulting red precipitate was filtered off and washed with cold water (3 × 10 mL) to yield 81% of two isomers (cis and trans) in a 1.5:8.5 ratio.

3.2.5.2. Piperidine (100%, 2 equiv) in Ethanol under Microwave-Assisted Protocol

2′-Hydroxy acetophenone (0.136 g, 1 mmol) and 4-aminodimethyl benzaldehyde (0.149 g, 1 mmol) were dissolved in absolute ethanol (7 mL) in a microwave reaction vessel (10 mL) fitted with a suitable magnetic stir bar, followed by the addition of piperidine (198 μL, 2 mmol). The microwave reaction vessel was capped properly and placed in the proper position in the microwave oven, and the pressure sensor was placed over the microwave vial. The dedicated microwave reactor was programmed to the following parameters: microwave 120 W, temperature 100 °C, internal pressure up to 10 bar, and 30 min reaction time. The reaction was stopped and cooled to ca. 50 °C via gas jet cooling (compressed air, 30 psi) automatically. The pressure sensor head was removed, and the reaction vessel was taken out from the microwave reactor and let to cool further down to rt for about 60 min. The desired product started to crystallize out forming shiny dark red crystals. The dark red crystals were collected in a suction filtration and washed with cold ethanol/water 1:1 (3 × 5 mL). The resulting crystals were air-dried to yield 87% of dark red shiny crystals, mp 170–172 °C, lit. 170–171 °C41. 1H NMR (DMSO-d6) δ 3.02 (s, 6H, 2CH3), 6.75 (d, J = 9.0 Hz, 2H, 3′-H, 5′-H), 6.95 (m, 1H, 5-H), 6.97 (d, J = 7.0 Hz, 1H, 3-H), 7.52 (m, 1H, 4-H), 7.73 (d, J = 9.5 Hz, 2H, 2′-H, 6′-H), 7.74 (d, J = 14.5 Hz, 1H, CH = CH-C = O), 7.81 (d, J = 15 Hz, 1H, CH=CH-C = O), 8.24 (d, J = 8.0 Hz, 1H, 6-H), 13.09 (s, 1H–OH). 13C NMR (DMSO-d6) δ 39.8, 111.9, 114.8, 122.0, 117.8, 119.0, 120.6, 121.8, 130.5, 131.5, 135.9, 147.0, 152.5, 162.4, and 193.3. DEPT-135 (DMSO-d6) δ 39.8, 111.9, 114.8, 117.8, 119.0, 130.5, 131.5, 135.9, 146.7. HPLC-UV-MS (m/z): 267.80 [M + H]+. Purity by HPLC-UV-MS: 96.74%.

3.2.5.3. General Procedure for the Synthesis of Chalcone Derivatives (8–17)

An equimolar concentration (1 mmol) of acetophenones and aldehyde derivatives was dissolved in absolute ethanol (7 mL) in a microwave reaction vessel (10 mL) fitted with a suitable magnetic stir bar. Piperidine (2 mmol) was added, and the reaction vessel was capped properly and placed in the microwave reactor. The dedicated microwave reactor was programmed to the following parameters: microwave 100 W, temperature 140 °C, internal pressure up to 10 bar, and 30 min of reaction time. After reaction completion, the reaction vessel was cooled via a gas jet cooler using compressed air at 30 psi. The pressure sensor head was removed; the reaction vessel was taken out from the microwave oven, and TLC monitored the reaction progress. The resulting mixture was allowed to cool further down to rt for about 60 min. The mixture was poured into crushed ice; the solid precipitate was filtered off by suction filtration and washed with cold ethanol/water (2:1) mixture (3 × 2 mL). The resulting crystals/powder were air-dried to yield the desired chalcones (8–17).

3.2.5.4. Spectral Data Analyses of the Synthesized Chalcone Derivatives (8–17)

(E)-3-(4-(diethylamino)phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (8): 1H NMR (600 MHz, DMSO-d6) δ 1.12 (t, J = 7.0 Hz, 6H), 3.42 (q, J = 7.0 Hz, 4H), 6.71 (d, J = 8.4 Hz, 2H), 6.99–6.93 (m, 2H), 7.51 (t, J = 7.7 Hz, 1H), 7.75–7.69 (m, 3H), 7.80 (d, J = 15.1 Hz, 1H), 8.23 (d, J = 7.8 Hz, 1H), 13.16 (s, 1H). 13C NMR (151 MHz, DMSO-d6) δ 12.62, 44.03, 111.37, 114.18, 117.86, 119.03, 120.66, 121.18, 130.49, 132.00, 135.89, 146.82, 150.16, 162.48, and 193.25. MS (m/z): 296.10 [M + H]+.

(E)-3-(4-(dimethylamino)phenyl)-1-(5-fluoro-2-hydroxyphenyl)prop-2-en-1-one (9): 1H NMR (500 MHz, DMSO-d6) δ 3.03 (s, 6H), 6.75 (d, J = 8.7 Hz, 2H), 6.98 (dd, J = 9.1, 4.7 Hz, 1H), 7.39 (td, J = 8.6, 3.1 Hz, 1H), 7.71 (d, J = 15.1 Hz, 1H), 7.77 (d, J = 8.6 Hz, 2H), 7.82 (d, J = 15.1 Hz, 1H), 8.11 (dd, J = 9.8, 3.2 Hz, 1H), 12.79 (s, 1H). 13C NMR (126 MHz, DMSO-d6) δ 39.82, 111.87, 114.86, 115.52, 115.70, 119.20, 119.26, 120.81, 120.86, 121.83, 122.93, 123.11, 131.83, 147.43, 152.67, 153.84, 155.70, 158.51, and 192.35. MS (m/z): 286.30 [M + H]+.

(E)-3-(4-(dimethylamino)phenyl)-1-(4-fluoro-2-hydroxyphenyl)prop-2-en-1-one (10): 1H NMR (500 MHz, DMSO-d6) δ 3.02 (s, 6H), 6.75 (d, J = 8.9 Hz, 2H), 6.85–6.78 (m, 2H), 7.71 (d, J = 15.1 Hz, 1H), 7.75 (d, J = 8.9 Hz, 2H), 7.82 (d, J = 15.1 Hz, 1H), 8.37 (dd, J = 8.8, 6.7 Hz, 1H), 13.62 (s, 1H). 13C NMR (126 MHz, DMSO-d6) δ 39.82, 104.20, 104.39, 106.76, 106.94, 111.88, 114.67, 117.83, 131.66, 133.33, 133.42, 146.98, 152.60, 164.92, 165.03, and 192.25. MS (m/z): 286.10 [M + H]+.

(E)-3-(4-(diethylamino)phenyl)-1-(2-hydroxy-5-methylphenyl)prop-2-en-1-one (11): 1H NMR (500 MHz, DMSO-d6) δ 1.12 (t, J = 7.0 Hz, 6H). 2.31 (s, 3H), 3.43 (q, J = 7.0 Hz, 4H), 6.72 (d, J = 8.6 Hz, 2H), 6.84 (d, J = 8.4 Hz, 1H), 7.33 (dd, J = 8.4, 2.1 Hz, 1H), 7.74–7.68 (m, 3H), 7.78 (d, J = 15.1 Hz, 1H), 8.06–8.03 (m, 1H), 12.95 (s, 1H). 13C NMR (126 MHz, DMSO-d6) δ 12.60, 20.14, 44.02, 111.33, 114.31, 117.61, 120.24, 121.23, 127.75, 130.08, 131.93, 136.75, 146.58, 150.09, 160.40, and 193.19. MS (m/z): 310.50 [M + H]+.

(E)-3-(4-(diethylamino)phenyl)-1-(5-fluoro-2-hydroxyphenyl)prop-2-en-1-one (12): 1H NMR (500 MHz, DMSO-d6) δ 12.86 (s, 1H), 8.10 (dd, J = 9.7, 3.2 Hz, 1H), 7.81 (d, J = 14.9 Hz, 1H), 7.74 (d, J = 8.4 Hz, 2H), 7.68 (d, J = 15.0 Hz, 1H), 7.39 (td, J = 8.6, 3.2 Hz, 1H), 6.97 (dd, J = 9.1, 4.6 Hz, 1H), 6.72 (d, J = 8.5 Hz, 2H), 3.43 (q, J = 7.1 Hz, 4H), 1.12 (t, J = 6.9 Hz, 6H). 13C NMR (126 MHz, DMSO-d6) δ 12.61, 44.04, 111.36, 114.20, 115.45, 115.64, 119.20, 119.26, 120.81, 120.86, 121.17, 122.86, 123.05, 132.25, 147.50, 150.30, 153.82, 158.54, and 192.25. MS (m/z): 314.10 [M + H]+.

(E)-3-(4-(diethylamino)phenyl)-1-(4-fluoro-2-hydroxyphenyl)prop-2-en-1-one (13): 1H NMR (500 MHz, DMSO-d6) δ 1.14 (t, J = 7.0 Hz, 6H), 3.44 (q, J = 7.0 Hz, 4H), 6.77–6.70 (m, 2H), 6.87–6.78 (m, 2H), 7.69 (d, J = 15.0 Hz, 1H), 7.77–7.71 (m, 2H), 7.83 (d, J = 15.0 Hz, 1H), 8.38 (dd, J = 8.8, 6.8 Hz, 1H), 13.71 (s, 1H). 13C NMR (126 MHz, DMSO-d6) δ: 12.95, 44.36, 104.54, 104. 73, 107.08, 107.25, 111.70, 114.35, 118.18, 121.46, 132.43, 133.58, 133.68, 147.40, 150.57, 165.29, 165.40, and 192.52. MS (m/z): 314.30 [M + H]+.

(E)-3-(4-(dimethylamino)phenyl)-1-phenylprop-2-en-1-one (14): 1H NMR (600 MHz, DMSO-d6) δ 3.00 (s, 6H), 6.74 (d, J = 8.6 Hz, 2H), 7.54 (t, J = 7.6 Hz, 2H), 7.64–7.59 (m, 2H), 7.71–7.66 (m, 3H), 8.10–8.07 (m, 2H). 13C NMR (151 MHz, DMSO-d6) δ 111.24, 111.93, 116.28, 122.14, 128.34, 128.81, 130.95, 132.65, 138.55, 145.37, 152.20, and 188.87. MS (m/z): 252.20 [M + H]+.

(2E,4E)-5-(4-(dimethylamino)phenyl)-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (15): 1H NMR (600 MHz, DMSO-d6) δ 2.97 (s, 6H), 6.74–6.71 (m, 2H), 6.96 (dd, J = 7.7, 6.5 Hz, 2H), 7.02 (dd, J = 15.3, 11.3 Hz, 1H), 7.17 (d, J = 15.3 Hz, 1H), 7.36 (d, J = 14.5 Hz, 1H), 7.46–7.43 (m, 2H), 7.52 (ddd, J = 8.4, 7.3, 1.6 Hz, 1H), 7.64 (dd, J = 14.5, 11.2 Hz, 1H), 7.99 (dd, J = 8.4, 1.7 Hz, 1H), 12.80 (s, 1H). 13C NMR (151 MHz, DMSO-d6) δ: 112.17, 117.95, 119.22, 120.82, 121.35, 122.20, 123.64, 129.38, 130.12, 136.00, 144.70, 147.25, 151.44, 162.15, and 193.25. MS (m/z): 294.20 [M + H]+.

(E)-1-(4-bromophenyl)-3-(4-(dimethylamino)phenyl)prop-2-en-1-one (16): 1H NMR (500 MHz, DMSO-d6) δ 3.00 (s, 6H), 6.73 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 15.3 Hz, 1H), 7.72–7.66 (m, 3H), 7.73 (d, J = 8.1 Hz, 2H), 8.03 (d, J = 8.1 Hz, 2H). 13C NMR (126 MHz, DMSO-d6) δ 39.82, 111.88, 115.80, 122.02, 126.64, 130.38, 131.07, 131.80, 137.52, 145.89, 152.28, and 187.81. MS (m/z): 330.10 [M + H]+.

(E)-1-(4-bromophenyl)-3-(4-(diethylamino)phenyl)prop-2-en-1-one (17): 1H NMR (500 MHz, DMSO-d6) δ 1.11 (t, J = 7.0 Hz, 6H), 3.42 (p, J = 7.4 Hz, 4H), 6.69 (d, J = 8.5 Hz, 2H), 7.55 (d, J = 15.3 Hz, 1H), 7.66 (q, J = 9.8, 7.9 Hz, 3H), 7.73 (d, J = 8.2 Hz, 2H), 8.02 (d, J = 8.2 Hz, 2H). 13C NMR (126 MHz, DMSO-d6) δ 12.43, 12.59, 149.81, 43.96, 44.10, 110.73, 111.31, 115.20, 121.28, 126.55, 130.34, 131.47, 131.79, 137.62, 145.95, and 187.75. MS (m/z): 358.10 [M + H]+.

3.4. Crystal Structure

Crystal structure of chalcone 7 revealed strong intramolecular hydrogen bonding (OH···O=C = 1.78 Å). The structure was found to be rigid, and the near-planarity molecular conformation in the crystal packing suggests the formation of J type; see Figure S46 and Table S1 (Supporting Information) and as previously reported.47−49

4. Conclusions

Twenty-six reaction procedures were employed for the synthesis of (E)-3-[4-(dimethylamino)phenyl]-1-(2-hydroxyphenyl)prop-2-en-1-one (7) as one of the most promising organic fluorescent dyes. Utilizing the published procedures including base (NaOH, KOH, Ba(OH)2·8H2O, K2CO3, and Et3N) and acid-catalyzed (SOCl2, HCl, HOAc, and Ac2O) synthetic methodologies failed in obtaining chalcone 7 in an efficient and productive way. Excess of piperidine in refluxing ethanol was the most promising condition; however, the product was obtained in a mixture of two stereoisomers (cis and trans) in an 8.5:1.5 ratio. In order to decrease the extended reaction time (>70 h), reduce the production of chemical waste and to prevent the formation of cis-isomer and other possible side products; the reaction was redesigned under microwave reaction condition protocols. With greater success, the desired product was obtained with excellent isolated yield (87%) and purity (97%), in a shorter reaction time (30 min). In order to investigate the scope and limitations of this novel protocol, it has been employed on other chalcones, which are structurally related to chalcone 7. Ten chalcone derivatives (8–17) were successfully synthesized in moderate to high isolated yields (32–79%). However, five chalcones (18–22) were inaccessible in the employed procedure.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.4c11066.

  • HPLC-UV-MS spectrum of chalcone 7 (Figure S1); 1H NMR Spectrum of chalcone 7 in DMSO-d6 (Figure S2); expanded 1H NMR spectrum of compound 7 in DMSO-d6 (Figure S3); 13C NMR spectrum of chalcone 7 in DMSO-d6 (Figure S4); DEPT-135 NMR spectrum of chalcone 7 in DMSO- d6 (Figure S5); NMR spectrum of chalcones 8–17 (Figures S6–S35); MS spectrum of chalcones 8–17 (Figures S36–S45); crystal data of chalcone 7: (A) ORTEP diagram, (B) crystal structure with hydrogen bond (up) and side view of the crystal (down), and (C) crystal packing diagram (Figure S46); crystal data and structure refinement for chalcone 7 (Table S1) (PDF)

  • Crystallization process of 4-(N,N-dimethylamino)-2′-hydroxychalcone (7) during the microwave reaction vessel cooling down to r.t. (MP4)

Author Contributions

Conceptualization, Y.B.; methodology, Y.B.; validation, Y.B. and A.H.I.; formal analysis, Y.B. and A.H.I.; investigation, Y.B. and A.H.I.; resources, Y.B.; data curation, Y.B. and A.H.I.; writing (original draft) preparation, Y.B. and A.H.I.; writing (review and editing), Y.B.; supervision, Y.B.; funding acquisition, Y.B. All authors have read and agreed to the published version of the manuscript.

This research was funded by SQU grants (IG/SCI/CHEM21/02, IG/SCI/CHEM24/01) and the Arab-German Young Academy of Sciences and Humanities (AGYA) grant (01DL20003).

The authors declare no competing financial interest.

Supplementary Material

ao4c11066_si_001.pdf (2.7MB, pdf)
ao4c11066_si_002.mp4 (123.2MB, mp4)

References

  1. Gillett A. J.; Privitera A.; Dilmurat R.; Karki A.; Qian D.; Pershin A.; Londi G.; Myers W. K.; Lee J.; Yuan J.; Ko S. J.; Riede M. K.; Gao F.; Bazan G. C.; Rao A.; Nguyen T. Q.; Beljonne D.; Friend R. H. The role of charge recombination to triplet excitons in organic solar cells. Nature. 2021, 597, 666–671. 10.1038/s41586-021-03840-5. [DOI] [PubMed] [Google Scholar]
  2. Inganäs O.; Sundström V. Solar energy for electricity and fuels. Ambio 2016, 45, 15–23. 10.1007/s13280-015-0729-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Hashmat U.; Rasool N.; Kausar S.; Altaf A. A.; Sultana S.; Tahir A. A. First-principles investigations of novel guanidine-based dyes. ACS Omega 2024, 9, 13917–13927. 10.1021/acsomega.3c09182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Lin C.; Liu Y.; Wang G.; Li K.; Xu H.; Zhang W.; Shao C.; Yang Z. Novel Dyes Design Based on First Principles and the Prediction of Energy Conversion Efficiencies of Dye-Sensitized Solar Cells. ACS Omega 2021, 6, 715–722. 10.1021/acsomega.0c05240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cruz L.; Basílio N.; Mateus N.; de Freitas V.; Pina F. Natural and synthetic flavylium-based dyes: The chemistry behind the color. Chem. Rev. 2022, 122, 1416–1481. 10.1021/acs.chemrev.1c00399. [DOI] [PubMed] [Google Scholar]
  6. Thant M. T.; Bhummaphan N.; Wuttiin J.; Puttipanyalears C.; Chaichompoo W.; Rojsitthisak P.; Punpreuk Y.; Böttcher C.; Likhitwitayawuid K.; Sritularak B. New phenolic glycosides from coelogyne fuscescens lindl. var. brunnea and their cytotoxicity against human breast cancer cells. ACS Omega 2024, 9, 7679–7691. 10.1021/acsomega.3c07048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Awla N. J.; Naqishbandi A. M.; Baqi Y. Preventive and therapeutic effects of silybum marianum seed extract rich in silydianin and silychristin in a rat model of metabolic syndrome. ACS Pharmacol. Transl. Sci. 2023, 6, 1715–1723. 10.1021/acsptsci.3c00171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Islam F.; Islam M. M.; Meem A. F. K.; Nafady M. H.; Islam M. R.; Akter A.; Mitra S.; Alhumaydhi F. A.; Emran T. B.; Khusro A.; Simal-Gandara J.; Eftekhari A.; Karimi F.; Baghayeri M. Multifaceted role of polyphenols in the treatment and management of neurodegenerative diseases. Chemosphere 2022, 307 (Pt 3), 136020 10.1016/j.chemosphere.2022.136020. [DOI] [PubMed] [Google Scholar]
  9. Alharbi K. S.; Almalki W. H.; Makeen H. A.; Albratty M.; Meraya A. M.; Nagraik R.; Sharma A.; Kumar D.; Chellappan D. K.; Singh S. K.; Dua K.; Gupta G. Role of medicinal plant-derived nutraceuticals as a potential target for the treatment of breast cancer. J. Food Biochem. 2022, 46, e14387 10.1111/jfbc.14387. [DOI] [PubMed] [Google Scholar]
  10. Youssef F. S.; Gamal El-Din M. I.; El-Beshbishy H. A.; Ashour M. L.; Singab A. B. Eremophila purpurascens: Anti-oxidant, anti-hyperglycemic, and hepatoprotective potential of its polyphenolic rich leaf extract and its LC–ESI–MS/MS chemical characterization and standardization. ACS Omega 2023, 8, 31928–31940. 10.1021/acsomega.3c03679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Valero L.; Gainche M.; Esparcieux C.; Delor-Jestin F.; Askanian H. Vegetal polyphenol extracts as antioxidants for the stabilization of PLA: toward fully biobased polymer formulation. ACS Omega 2024, 9, 7725–7736. 10.1021/acsomega.3c07236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Zhuang C.; Zhang W.; Sheng C.; Zhang W.; Xing C.; Miao Z. Chalcone: A privileged structure in medicinal chemistry. Chem. Rev. 2017, 117, 7762–7810. 10.1021/acs.chemrev.7b00020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Singh P.; Anand A.; Kumar V. Recent developments in biological activities of chalcones: A mini review. Eur. J. Med. Chem. 2014, 85, 758–777. 10.1016/j.ejmech.2014.08.033. [DOI] [PubMed] [Google Scholar]
  14. Baramaki I.; Altıntop M. D.; Arslan R.; Altınok F. A.; Özdemir A.; Dallali I.; Hasan A.; Türkmen N. B. Design, synthesis, and in vivo evaluation of a new series of indole-chalcone hybrids as analgesic and anti-inflammatory agents. ACS Omega 2024, 9, 12175–12183. 10.1021/acsomega.4c00026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Apiraksattayakul S.; Pingaew R.; Leechaisit R.; Prachayasittikul V.; Ruankham W.; Songtawee N.; Tantimongcolwat T.; Ruchirawat S.; Prachayasittikul V.; Prachayasittikul S.; Phopin K. Aminochalcones attenuate neuronal cell death under oxidative damage via sirtuin 1 activity. ACS Omega 2023, 8, 33367–33379. 10.1021/acsomega.3c03047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Michalkova R.; Kello M.; Cizmarikova M.; Bardelcikova A.; Mirossay L.; Mojzis J. Chalcones and gastrointestinal cancers: Experimental evidence. Int. J. Mol. Sci. 2023, 24, 5964. 10.3390/ijms24065964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Dadi V.; Malla R. R.; Siragam S. Natural and synthetic chalcones: Potential impact on breast cancer. Crit. Rev. Oncog. 2023, 28, 27–40. 10.1615/CritRevOncog.2023049659. [DOI] [PubMed] [Google Scholar]
  18. Birsa M. L.; Sarbu L. G. Hydroxy chalcones and analogs with chemopreventive properties. Int. J. Mol. Sci. 2023, 24, 10667. 10.3390/ijms241310667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mahboubi-Rabbani M.; Zarei R.; Baradaran M.; Bayanati M.; Zarghi A. Chalcones as potential cyclooxygenase-2 inhibitors: A review. Anticancer Agents Med. Chem. 2024, 24, 77–95. 10.2174/0118715206267309231103053808. [DOI] [PubMed] [Google Scholar]
  20. Maisto M.; Marzocchi A.; Keivani N.; Piccolo V.; Summa V.; Tenore G. C. Natural chalcones for the management of obesity disease. Int. J. Mol. Sci. 2023, 24, 15929. 10.3390/ijms242115929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sokmen M.; Khan M. A. The antioxidant activity of some curcuminoids and chalcones. Inflammopharmacology 2016, 24, 81–86. 10.1007/s10787-016-0264-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Elkanzi N. A. A.; Hrichi H.; Alolayan R. A.; Derafa W.; Zahou F. M.; Bakr R. B. Synthesis of chalcones derivatives and their biological activities: A review. ACS Omega 2022, 7, 27769–27786. 10.1021/acsomega.2c01779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hofmann E.; Webster J.; Do T.; Kline R.; Snider L.; Hauser R.; Higginbottom G.; Campbell A.; Ma L.; Paula S. Hydroxylated chalcones with dual properties: Xanthine oxidase inhibitors and radical scavengers. Bioorg. Med. Chem. 2016, 24, 578–587. 10.1016/j.bmc.2015.12.024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schmidt J. G. Ueber die Einwirkung von Aceton auf Furfurol und auf Bittermandelöl bei Gegenwart von Alkalilauge. Ber. Dtsch. Chem. Ges. 1881, 14, 1459–1461. 10.1002/cber.188101401306. [DOI] [Google Scholar]
  25. Claisen L.; Claparède A. Condensationen von Ketonen mit Aldehyden. Ber. Dtsch. Chem. Ges. 1881, 14, 2460–2468. 10.1002/cber.188101402192. [DOI] [Google Scholar]
  26. Kappe C. O. Controlled microwave heating in modern organic synthesis. Angew. Chem., Int. Ed. 2004, 43, 6250–6284. 10.1002/anie.200400655. [DOI] [PubMed] [Google Scholar]
  27. Kappe C. O. My twenty years in microwave chemistry: from kitchen ovens to microwaves that aren’t microwaves. Chem. Rec. 2019, 19, 15–39. 10.1002/tcr.201800045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. De la Hoz A.; Loupy A.. Microwaves in Organic Synthesis, 3rd ed.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2013. 10.1039/B411438H. [DOI] [Google Scholar]
  29. Gawande M. B.; Shelke S. N.; Zboril R.; Varma R. S. Microwave-assisted chemistry: synthetic applications for rapid assembly of nanomaterials and organics. Acc. Chem. Res. 2014, 47, 1338–1348. 10.1021/ar400309b. [DOI] [PubMed] [Google Scholar]
  30. Baqi Y. Recent advances in microwave-assisted copper-catalyzed cross-coupling reactions. Catalysts. 2021, 11, 46. 10.3390/catal11010046. [DOI] [Google Scholar]
  31. Salih K. S. M.; Baqi Y. Microwave-Assisted palladium-catalyzed cross-coupling reactions: generation of carbon–carbon bond. Catalysts. 2020, 10, 4. 10.3390/catal10010004. [DOI] [Google Scholar]
  32. Perdana F.; Eryanti Y.; Zamri A. Synthesis and toxicity assessments some para-methoxy chalcones derivatives. Procedia Chem. 2015, 16, 129–133. 10.1016/j.proche.2015.12.040. [DOI] [Google Scholar]
  33. Ismail A. H.; Abdula A. M.; Mohammed M. T. Al-Bayati. 1,3,5-trisubstituted-1H-pyrazole derivatives as new antimicrobial agents: Synthesis, characterization and docking study. Int. J. Chem. Sci. 2017, 15, 126. [Google Scholar]
  34. Ismail A. H.; Abdula A. M.; Tomi I. H. R.; Al-Daraji A. H. R.; Baqi Y. Synthesis, antimicrobial evaluation and docking study of novel 3,5-disubstituted-2-isoxazoline and 1,3,5-trisubstituted-2-pyrazoline derivatives. Med. Chem. 2021, 17, 462–473. 10.2174/1573406415666191107121757. [DOI] [PubMed] [Google Scholar]
  35. Zahid N. I.; Mahmood M. S.; Subramanian B.; Mohd Said S.; Abou-Zied O. K. New insight into the origin of the red/near-infrared intense fluorescence of a crystalline 2-hydroxychalcone derivative: A comprehensive picture from the excited-state femtosecond dynamics. J. Phys. Chem. Lett. 2017, 8, 5603–5608. 10.1021/acs.jpclett.7b02601. [DOI] [PubMed] [Google Scholar]
  36. Zhu T.; Du J.; Cao W.; Fan J.; Peng X. Microenvironment-sensitive fluorescent dyes for recognition of serum albumin in urine and imaging in living cells. Ind. Eng. Chem. Res. 2016, 55, 527–533. 10.1021/acs.iecr.5b04214. [DOI] [Google Scholar]
  37. Karki R.; Thapa P.; Yoo H. Y.; Kadayat T. M.; Park P. H.; Na Y.; Lee E.; Jeon K. H.; Cho W. J.; Choi H.; Kwon Y.; Lee E. S. Dihydroxylated 2,4,6-triphenyl pyridines: Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure–activity relationship study. Eur. J. Med. Chem. 2012, 49, 219–228. 10.1016/j.ejmech.2012.01.015. [DOI] [PubMed] [Google Scholar]
  38. Tran T. D.; Do T. H.; Tran N. C.; Ngo T. D.; Huynh T. N. P.; Tran C. D.; Thai K. M. Synthesis and anti-Methicillin Resistant Staphylococcus aureus activity of substituted chalcones alone and in combination with non-beta-lactam antibiotics. Bioorg. Med. Chem. Lett. 2012, 22, 4555–4560. 10.1016/j.bmcl.2012.05.112. [DOI] [PubMed] [Google Scholar]
  39. Yeom J. E.; Kumar M. R.; Lee S.; Lee J. B.; Park H. R. Synthesis of flavanol-4-ol and its spectroscopic properties in aqueous solution. Bull. Korean Chem. Soc. 2011, 32, 4092–4094. 10.5012/bkcs.2011.32.11.4092. [DOI] [Google Scholar]
  40. Javad Poursharifi M.; Mojtahedi M. M.; Saeed Abaee M.; Hashemi M. M. The first in situ synthesis of 1,3-dioxan-5-one derivatives and their direct use in Claisen-Schmidt reactions. Heterocycl. Commun. 2019, 25, 85–90. 10.1515/hc-2019-0013. [DOI] [Google Scholar]
  41. Petrov O.; Ivanova Y.; Gerova M. SOCl2/EtOH: Catalytic system for synthesis of chalcones. Catal. Comm. 2008, 9, 315–316. 10.1016/j.catcom.2007.06.013. [DOI] [Google Scholar]
  42. Yan H. P.; Huang D. S.; Zhang J. C.; Huang R. N.; Fu Y. W.; Wang W. S. Synthesis of three different type of chalcone derivatives. Adv. Mater. Res. 2014, 1033, 81. 10.4028/www.scientific.net/AMR.1033-1034.81. [DOI] [Google Scholar]
  43. Lu C.; Liu Q.; Gu P.; Chen D.; Zhou F.; Li H.; Xu Q.; Lu J. Improving the electrical memory performance of pyrazoline moiety via the preparation of its hyperbranched copolymer. Polym. Chem. 2014, 5, 2602–2610. 10.1039/c3py01588b. [DOI] [Google Scholar]
  44. Venkatesan P.; Sumathi S. Piperidine mediated synthesis of n-heterocyclic chalcones and their antibacterial activity. J. Heterocycl. Chem. 2010, 47, 81–84. 10.1002/jhet.268. [DOI] [Google Scholar]
  45. Baqi Y.; Müller C. E. Synthesis of alkyl- and aryl-amino-substituted anthraquinone derivatives by microwave-assisted copper(0)-catalyzed Ullmann coupling reactions. Nat. Protoc. 2010, 5, 945–953. 10.1038/nprot.2010.63. [DOI] [PubMed] [Google Scholar]
  46. Song Z.; Kwok R. T. K.; Zhao E.; He Z.; Hong Y.; Lam J. W. Y.; Liu B.; Tang B. Z. A Ratiometric fluorescent probe based on ESIPT and AIE processes for alkaline phosphatase activity assay and visualization in living cells. ACS Appl. Mater. Interfaces. 2014, 6, 17245–17254. 10.1021/am505150d. [DOI] [PubMed] [Google Scholar]
  47. Cheng X.; Wang K.; Huang S.; Zhang H.; Zhang H.; Wang Y. Organic crystals with near-infrared amplified spontaneous emissions based on 2′-hydroxychalcone derivatives: subtle structure modification but great property change. Angew. Chem., Int. Ed. 2015, 54, 8369–8373. 10.1002/anie.201503914. [DOI] [PubMed] [Google Scholar]
  48. Würthner F.; Kaiser T. E.; Saha-Möller C. R. J-aggregates: from serendipitous discovery to supramolecular engineering of functional dye materials. Angew. Chem., Int. Ed. 2011, 50, 3376–3410. 10.1002/anie.201002307. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

ao4c11066_si_001.pdf (2.7MB, pdf)
ao4c11066_si_002.mp4 (123.2MB, mp4)

Articles from ACS Omega are provided here courtesy of American Chemical Society

RESOURCES