Synthesis of coumarin-3-carboxylic acids in waste curd water: A green approach European Journal of Chemistry 14 (4) (2023) 439-444 European Journal of Chemistry ISSN 2153-2249 (Print) / ISSN 2153-2257 (Online) – Copyright © 2023 The Authors – Atlanta Publishing House LLC – Printed in the USA. This work is published and licensed by Atlanta Publishing House LLC – CC BY NC – Some Rights Reserved. https://dx.doi.org/10.5155/eurjchem.14.4.439-444.2471 European Journal of Chemistry View Journal Online View Article Online Synthesis of coumarin-3-carboxylic acids in waste curd water: A green approach Nitin Bhaidas Sonawane 1,*, Jamatsing Darbarsing Rajput 2 and Dilip Ramsing Patil 3 1 Department of Chemistry, Bahujan Samaj Shikshan Prasarak Mandal’s Arts, Commerce and Science College, Songir, Dhule, 424309, Maharashtra, India 2 Department of Chemistry, Bhagirathibai Purnapatre Arts, Sitabai Mangilal Agrawal Science, Kasturbai Khandu Chaudhari Commerce College, Chalisgaon, Jalgaon, 424101, Maharashtra, India 3 Department of Chemistry, Rasiklal Chunilal Patel Education Trust’s Rasiklal Chunilal Patel Arts, Commerce & Science College, Shirpur, Dhule, 425405, Maharashtra, India * Corresponding author at: Department of Chemistry, Bahujan Samaj Shikshan Prasarak Mandal’s Arts, Commerce and Science College, Songir, Dhule, 424309, Maharashtra, India. e-mail: prof.nbsonawane@gmail.com (N.B. Sonawane). 10.5155/eurjchem.14.4.439-444.2471 Received: 30 July 2023 Received in revised form: 21 August 2023 Accepted: 17 September 2023 Published online: 31 December 2023 Printed: 31 December 2023 An efficient and green protocol has been developed for the synthesis of derivatives of coumarin-3-carboxylic acid using waste curd water as a catalytic solvent. Curd water successfully catalyzes the reaction of 2-hydroxybenzaldehydes with dimethyl malonate under ultrasonic irradiation (40 °C) to construct different scaffolds of coumarin-3- carboxylic acid, with good to outstanding yields. The use of biodegradable solvents, sustainability, low reaction duration, mild reaction conditions without metals and Lewis acids, excellent yields, and compatibility with a wide range of electronically diverse substrates are all advantages of this synthesis process. Acidic curd water, which acts as a biological catalyst as well as a solvent for the reaction under ultrasonic irradiation, may be a better green alternative to some standard methods for synthesizing coumarin-3-carboxylic acids. Sonication Curd water Green synthesis Catalytic solvent 3-Carboxycoumarins Coumarin-3-carboxylic acid Cite this: Eur. J. Chem. 2023, 14(4), 439-444 Journal website: www.eurjchem.com 1. Introduction New catalytic synthetic strategies in the field of chemical science that meet increasingly stringent environmental constraints are in high demand within the pharmaceutical and chemical industries. Developing cleaner, safer, and more environmentally friendly chemical approaches is a crucial objective for chemists [1]. As a result of the presence of this heterocyclic nucleus in numerous natural compounds, the synthesis of coumarins and their derivatives has garnered significant interest from organic and medicinal chemists for many years. These compounds are widely used as precursors for the synthesis of crucial organic compounds in the pharma- ceutical industry. Coumarin and its derivatives showcase a wide range of biological activities, including antioxidative, anti- Alzheimer, antidiabetic, anti-HIV, antiallergic, antihelmintic, sedative, and hypnotic [2-5]. Furthermore, they function as anticancer agents by inhibiting the monocarboxylate trans- porter, act as anticoagulants (targeting the coagulation enzymes FXa and Thr involved in thrombosis), and display antimicrobial efficacy against Staphylococcus aureus, Bacillus subtilis, and Escherichia coli [6,7] (Figure 1). In addition, they have applications in materials science, agrochemicals, food industry, perfumery, and the cosmetic sector [8]. Coumarins containing a carboxyl group in a heterocyclic backbone, namely, coumarin-3-carboxylic acids (also known as 3-carboxycoumarins), represent an important class of biologically valuable pharmacological compounds, as well as have some specific applications in a wide range of possibilities over other coumarin derivatives (esters and amides). In particular, derivatives of coumarin-3-carboxylic acid are utilized for the following purposes: (i) detecting the hydroxyl radical (·OH) generated by γ-irradiation or by chemical reactions in aqueous solutions [9], (ii) addressing neurological disorders such as neuropathic pain, epilepsy, and depression [10], and (iii) serving as fluorescent probes and sensitizers for triplet oxygen [11]. Thus, such chemical compounds can be considered promising new achievements for further innovative work. Numerous pathways are known in the literature for the synthesis of coumarin-3-carboxylic acids. A two-step method developed by Fringuelli et al. in 2003 involved the Knoevenagel ABSTRACT RESEARCH ARTICLE KEYWORDS https://dx.doi.org/10.5155/eurjchem.14.4.439-444.2471 https://www.eurjchem.com/ https://dx.doi.org/10.5155/eurjchem.14.4.439-444.2471 mailto:prof.nbsonawane@gmail.com http://www.eurjchem.com/ https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.14.4.439-444.2471&domain=pdf&date_stamp=2023-12-31 440 Sonawane et al. / European Journal of Chemistry 14 (4) (2023) 439-444 2023 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.14.4.439-444.2471 Figure 1. Coumarins containing a carboxyl group in a heterocyclic backbone. condensation of salicylaldehydes with malononitrile in basic medium followed by a pinner reaction and acid hydrolysis [12]. Scott et al. developed a one-pot green synthesis of coumarin-3- carboxylic acid from 2-hydroxybenzaldehydes and Meldrum’s acid at room temperature with catalytic amounts of ammonium acetate [13]. A variety of catalytic approaches have been adopted for Knoevenagel aldehyde condensation with an active methylene compound such as K10-ZnCl2 [14], Yb(OTf)3 [15], potassium 1,2,3,6-tetrahydrophthalimide [16], silica gel [17], K2CO3, NaN3 [18], SnCl2 [19] and ZrOCl2·8H2O [20]. In recent years, great effort has been expended to produce coumarin derivatives using greener approaches using ionic liquid [21], deep eutectic solvent (DES) [22], natural kaolinitic clay (EPZG, EPZ10) [23], aqueous extract of pods of acacia concinna [24], water extract of Nilgiri bark ash (WENBA) [25], and water extract of banana (WEB) [26]. Although these protocols reported by others definitely deserve of their own, still they suffer from a variety of demerits, such as a long reaction time, low yields, and the need of action for purification of adducts. Therefore, the exploration for a lot of general, clean, efficient, and high-yielding routes for synthesis remains a sound exercise in organic chemistry and represents a field of research of current and growing interest. The dairy industry stands out as one of India’s most polluting sectors. The dairy industry in India has experienced rapid growth due to the growing demand for milk and other dairy products. Consequently, this growth has led to the disposal of large amounts of waste in nearby water bodies. Dairy wastewater contains substantial quantities of bio- chemical oxygen demand, chemical oxygen demand, as well as organic and inorganic chemicals. The improper discharge of this wastewater into water bodies without proper treatment can cause significant environmental problems [27]. Recently, we have investigated the effective utilization of waste curd water as a catalytic solvent in organic synthesis. Curd water, a liquid by-product of the curdling process that is separated from curd during the cheese or yogurt production process, is being considered. The reaction between 2-hydroxybenzaldehydes (1) and dimethyl malonate (2), facilitated by ultrasound irradiation at 40 °C, produces distinct scaffolds of coumarin-3-carboxylic acid. This process highlights the development of an environ- mentally friendly synthesis approach for coumarin-3- carboxylic acids, aided by ultrasound (Scheme 1). 2. Experimental 2.1. Instrumentation Sonication was performed in a Labman Probe Sonicator with a frequency of 25 kHz and a nominal power of 200 W. Melting points were determined in the open capillaries and were not corrected. IR spectra were taken as KBr pellets on a Shimadzu FT-IR spectrophotometer (FT-IR 8400S). The 1H and 13C NMR spectra were recorded at room temperature on a Bruker Avance II 400 NMR spectrometer at 400 and 100 MHz, respectively, using DMSO-d6 as NMR solvent. Chemical shifts are given in ppm. The Waters Q-Tof Micromass LC-MS spectro- meter was used to record the mass spectra. 2.2. Materials Dimethyl malonate and 2-hydroxybenzaldehydes were obtained from commercial suppliers of Sigma-Aldrich and used without further purification. Curd water was prepared as a catalytic solvent in the laboratory. Thin layer chromatography (TLC) on silica gel plates (Merck, silica gel 60F254, ready to use) was used to monitor the progress of the synthesis, with ethyl acetate: n-hexane (1:4) used as the eluent. 2.3. Procedure for the preparation of curd water solvent The curd was synthesized under aseptic conditions with a 1% lactic acid bacteria starter culture in 100 mL of pasteurized warm milk and incubated at 37 °C for 48 hours to activate the culture and establish the curd. The water was taken from the freshly made curd by filtering it through a muslin cloth, and the filtered turbid liquid was then collected. The turbid liquid was centrifuged for 15 minutes at 4000 revolutions per minute. The turbid liquid was filtered using ordinary Whatman paper, producing a pale-yellow liquid suitable for further reactions [28]. 2.4. General procedure for the synthesis of derivatives of coumarin-3-carboxylic acid A mixture of 2-hydroxybenzaldehyde (1.0 mmol) and dimethyl malonate (1.0 mmol) in 5 mL of curd water was prepared. The mixture was sonicated at appropriate times and the course of the reaction was monitored using TLC on silica gel with ethyl acetate: n-hexane (1:4) as an eluent. After completion of the reaction, the resulting mixture was poured into the ice-water mixture, filtered off, washed with cold water, and the crude product was obtained as a solid. The solid product was recrystallized from methanol and pure derivatives of coumarin-3-carboxylic acid (3a-3j) were obtained. The authenticity of the products was established by comparing their melting points with literature values (Table 1) and by analyzing the spectroscopic data of 1H and 13C NMR, IR, and MS. 2-Oxo-2H-chromene-3-carboxylic acid (3a): Color: White. Yield: 95%. M.p.: 192-194 °C. FT-IR (KBr, ν, cm-1): 3050 (C-H) (aromatic), 1751 (C=O) (ester), 1687 (C=O) (acid), 1500 (C=C) (aromatic). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 12.81 (s, 1H, OH), 8.71 (s, 1H, Ar-H), 7.83-7.81 (d, 1H, Ar-H), 7.71-7.67 (t, 1H, Ar-H), 7.37-7.36 (t, 1H, Ar-H), 7.39-7.38 (d, 1H, Ar-H). 13C NMR (100 MHz, CDCl3, δ, ppm): 115.90, 117.70, 117.85, 124.52, 130.10, 134.80, 147.87, 153.92, 156.81. MS (EI, m/z): 191.11 (M+). 7-(Diethylamino)-2-oxo-2H-chromene-3-carboxylic acid (3b): Color: Pale yellow. Yield: 91%. M.p.: 220-222 °C. FT-IR (KBr, ν, cm-1): 3456 (N-C) (amine), 3024 (C-H) (aromatic), 1760 Sonawane et al. / European Journal of Chemistry 14 (4) (2023) 439-444 441 2023 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.14.4.439-444.2471 R CHO OH O O OO O O O OH R Curd water )))))), 40 oC 1 2 3a - 3j Scheme 1. Green synthesis of coumarin-3-carboxylic acids. (C=O) (ester), 1685 (C=O) (acid), 1515 (C=C) (aromatic). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 12.24 (s, 1H, OH), 7.58 (s, 1H, Ar-H), 7.57 (s, 1H, Ar-H), 6.76-6.74 (d, 1H, Ar-H), 6.54-6.53 (d, 1H, Ar-H), 3.53-3.48 (m, 4H, 2CH2), 1.23-1.20 (m, 6H, 2CH3). 13C NMR (100 MHz, CDCl3, δ, ppm): 12.11, 44.04, 105.91, 107.20, 111.24, 131.55, 148.30, 151.85, 160.10, 165.65. MS (EI, m/z): 261.15 (M). 7,8-Dihydroxy-2-oxo-2H-chromene-3-carboxylic acid (3c): Color: White. Yield: 94%. M.p.: 192-194 °C. FT-IR (KBr, ν, cm-1): 3472-3240 (OH) (aromatic), 3016 (C-H) (aromatic), 1768 (C=O) (ester), 1678 (C=O) (acid), 1517 (C=C) (aromatic). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 12.17 (s, 1H, OH), 11.04 (s, 1H, Ar-H), 8.75 (d, 1H, Ar-H), 8.16 (d, 1H, Ar-H), 6.30 (s, 1H, OH), 6.21 (s, 1H, OH). 13C NMR (100 MHz, CDCl3, δ, ppm): 94.01, 98.50, 103.11, 107.20, 145.22, 156.16, 157.88, 160.35, 164.12, 166.18. MS (EI, m/z): 245.14 (M+ + Na). 5,7-Dihydroxy-2-oxo-2H-chromene-3-carboxylic acid (3d): Color: White. Yield: 87%. M.p.: 194-196 °C. FT-IR (KBr, ν, cm-1): 3501 (OH) (aromatic), 3018 (C-H) (aromatic), 1778 (C=O) (ester), 1695 (C=O) (acid), 1547 (C=C) (aromatic). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 10.77 (s, 1H, OH), 8.64 (s, 1H, Ar-H), 8.15 (s, 1H, Ar-H), 7.20 (s, 1H, Ar-H), 6.88 (s, 1H, OH), 6.86 (s, 1H, OH). 13C NMR (100 MHz, CDCl3, δ, ppm): 94.09, 98.55, 102.83, 107.44, 145.22, 157.34, 158.20, 160.38, 164.18, 165.70. MS (EI, m/z): 245.14 (M++ Na). 6-Chloro-2-oxo-2H-chromene-3-carboxylic acid (3e): Color: Pale yellow. Yield: 92%. M.p.: 120-122 °C. FT-IR (KBr, ν, cm-1): 3021 (C-H) (aromatic), 1751 (C=O) (ester), 1682 (C=O) (acid), 1512 (C=C) (aromatic), 875 (C-Cl). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 8.68 (s, 1H, OH), 7.99 (s, 1H, Ar-H), 7.89 (s, 1H, Ar-H), 7.66-7.63 (d, 1H, Ar-H), 7.39-7.36 (d, 1H, Ar-H). 13C NMR (100 MHz, CDCl3, δ, ppm): 117.84, 119.11, 119.22, 128.26, 128.82, 133.48, 147.09, 152.97, 156.16, 163.51. MS (EI, m/z): 225.11 (M+). 8-Hydroxy-2-oxo-2H-chromene-3-carboxylic acid (3f): Color: Pale yellow. Yield: 92%. M.p.: 200-202 °C. FT-IR (KBr, ν, cm-1): 3482 (OH) (aromatic), 3031 (C-H) (aromatic), 1781 (C=O) (ester), 1686 (C=O) (acid), 1527 (C=C) (aromatic). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 11.57 (s, 1H, OH), 8.61 (s, 1H, Ar-H), 7.60 (t, 1H, Ar-H), 6.80-6.79 (d, 1H, Ar-H), 6.77 (d, 1H, Ar-H), 6.69 (s, 1H, OH). 13C NMR (100 MHz, CDCl3, δ, ppm): 107.85, 145.06, 157.46, 158.08, 159.58, 165.63. MS (EI, m/z): 226.12 (M++ Na). 6-Bromo-2-oxo-2H-chromene-3-carboxylic acid (3g): Color: Pale creamy solid. Yield: 93%. M.p.: 192-194 °C. FT-IR (KBr, ν, cm-1): 3028 (C-H) (aromatic), 1752 (C=O) (ester), 1680 (C=O) (acid), 1518 (C=C) (aromatic), 878 (C-Br). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 8.74 (s, 1H, OH), 8.10 (s, 1H, Ar-H), 7.49 (s, 1H, Ar-H), 7.19-7.17 (d, 1H, Ar-H), 3.48-3.46 (d, 1H, Ar-H). 13C NMR (100 MHz, CDCl3, δ, ppm): 116.37, 118.67, 119.50, 123.52, 131.09, 131.29, 147.01, 153.37, 159.29, 163.46. MS (EI, m/z): 268.77 (M++ Na). 5-Isopropyl-8-methyl-2-oxo-2H-chromene-3-carboxylic acid (3h): Color: White. Yield: 90%. M.p.: 216-218 °C. FT-IR (KBr, ν, cm-1): 3022 (C-H) (aromatic), 3045-2914 (C-H) (aromatic, methyl), 1764 (C=O) (ester), 1679 (C=O) (acid), 1530 (C=C) (aromatic). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 12.43 (s, 1H, OH), 9.29 (s, 1H, Ar-H), 7.60-7.58 (d, 1H, Ar-H), 7.31-7.29 (d, 1H, Ar-H), 3.57-3.52 (m, 1H, Ar-H), 2.43 (s, 3H, CH3), 1.36-1.34 (d, 6H, 2CH3). 13C NMR (100 MHz, CDCl3, δ, ppm): 116.37, 118.67, 119.50, 123.52, 131.09, 131.29, 147.01, 153.37, 159.29, 163.46. MS (EI, m/z): 247.23 (M++ Na). 8-Isopropyl-5-methyl-2-oxo-2H-chromene-3-carboxylic acid (3i): Color: White. Yield: 86%. M.p.: 170-172 °C. FT-IR (KBr, ν, cm-1): 3051 (C-H) (aromatic), 3034-2894 (C-H) (aromatic, methyl), 1758 (C=O) (ester), 1682 (C=O) (acid), 1510 (C=C) (aromatic). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 8.69 (s, 1H, OH), 8.14 (s, 1H, Ar-H), δ 7.95-7.94 (d, 1H, Ar-H), 7.68 (d, 1H, Ar-H), 7.66 (m, 1H, CH), 7.42 (s, 3H, CH3), 2.54 (d, 6H, 2CH3). 13C NMR (100 MHz, CDCl3, δ, ppm): 11.65, 22.11, 25.95, 113.23, 116.44, 125.18, 130.91, 133.01, 135.46, 145.19, 152.32, 163.07, 168.39. MS (EI, m/z): 247.23 (M++ Na). 6-Allyl-8-methoxy-2-oxo-2H-chromene-3-carboxylic acid (3j): Color: White. Yield: 85%. M.p.: 172-174 °C. FT-IR (KBr, ν, cm-1): 3068 (C-H) (aromatic), 1764 (C=O) (ester), 1692 (C=O) (acid), 1510 (C=C) (aromatic)., 1654 (C=C) (alkene), 1034 (C-O) (methoxy). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 8.60 (s, 1H, OH), 7.15 (s, 1H, Ar-H), 6.01 (s, 1H, Ar-H), 6.00 (s, 1H, Ar-H), 5.98-5.94 (m, 1H, =CH), 5.92 (d, 2H, =CH2), 3.93 (s, 3H, CH3), 3.42 (d, 2H, CH2). 13C NMR (100 MHz, CDCl3, δ, ppm): 39.31, 55.92, 116.33, 116.42, 118.89, 119.91, 136.52, 142.67, 146.07, 148.49, 156.65, 163.75. MS (EI, m/z): 261.21 (M++ Na). 3. Results and discussion 3.1. Synthesis of 3-carboxycoumarin derivatives Our contribution aims to broaden the range of methods that can be used to synthesize coumarin-3-carboxylic acids and to describe how a new catalytic system can be used in their synthesis. According to our research, substituted benz- aldehydes react with dimethyl malonate in the presence of curd water under ultrasonic radiation to produce the respective derivatives of coumarin-3-carboxylic acid in good to out- standing yields (Scheme 1). We first evaluated the viability of this reaction using a model condensation of 2-hydroxybenzaldehyde and dimethyl malonate under a variety of reaction conditions. As part of our research on the use of curd water as a catalytic solvent in synthesis, we attempted a curd-water-catalyzed condensation reaction by conventional heating. However, only good yields of the preferred product were obtained because of the difficult reaction conditions, which included high temperatures and a long reaction time. We performed the same reaction under ultrasonic irradiation as an intriguing method to speed up chemical reactions. The results were striking: an enhancement in the yield of the target product was observed, and the entire transformation was achieved within a mere hour. We coupled the catalyst and ultrasonic irradiation in this process to accelerate both the rate of the chemical reaction and the catalyst efficiency. Different aromatic aldehydes were exposed to this technique to investigate the scope of the reaction. All of the reactions went well, yielded high volumes, and created no unwanted byproducts. According to a standard approach, the reaction of 2-hydroxybenzaldehyde (1 mmol) and dimethyl malonate (1 mmol) in the presence of curd water (5 mL) under ultrasonic irradiation (1 hour) produces compound 3a with a 95% yield (Table 1, entry 1). 442 Sonawane et al. / European Journal of Chemistry 14 (4) (2023) 439-444 2023 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.14.4.439-444.2471 Table 1. Synthesis of coumarin-3-carboxylic acids in waste curd water with ultrasonic irradiation. Entry Aldehyde Product Yield (%) Melting point (oC) Reference Found Reported 1 2-Hydroxybenzaldehyde 3a 95 192-194 190-191 [9] 2 4-(Diethylamino)-2-hydroxybenzaldehyde 3b 91 220-222 224-225 [20] 3 2,3,4-Trihydroxybenzaldehyde 3c 94 192-194 190-192 [26] 4 2,4,6-Trihydroxybenzaldehyde 3d 87 194-196 190-192 [25] 5 5-Chloro-2-hydroxybenzaldehyde 3e 92 120-122 121-122 [9] 6 2,3-Dihydroxybenzaldehyde 3f 92 200-202 204-206 [26] 7 5-Bromo-2-hydroxybenzaldehyde 3g 93 192-194 191-193 [23] 8 2-Hydroxy-6-isopropyl-3-methylbenzaldehyde 3h 90 216-218 212-214 [6] 9 2-Hydroxy-3-isopropyl-6-methylbenzaldehyde 3i 86 170-172 167-169 [25] 10 5-Allyl-2-hydroxy-3-methoxybenzaldehyde 3j 85 172-174 172-174 [26] Table 2. Comparison of our results with some previously reported data for the synthesis of compound 3a. Catalyst Condition Yield % Reference K2CO3 (10 mol%)/H2O Stirring at RT for 20 hours 79 [18] SnCl2·2H2O Solvent free 80 °C, 60 minutes 80 [19] WEB (5%) Ethanol, 440 minutes 94 [22] Natural clay, EPZ10 M.W./5 minutes 71 [23] WENBA 3.5 hours 90 [25] Curd water ))))), 40 °C, 1 hour 95 This work Scheme 2. Plausible mechanism for the synthesis of 3-carboxycoumarin derivatives using curd water. A Knoevenagel condensation of substituted benzaldehydes and dimethyl malonate followed by intramolecular cyclization can be used to outline the mechanism for the formation of coumarin-3-carboxylic acids. We believe that the lactic acid present in the curd water solution coordinates with carbonyl oxygen and activates the carbonyl group for nucleophilic attack (Scheme 2). Numerous substituted benzaldehydes were examined to investigate the impact of various substituents on the generality of the reaction. The results are summarized in Table 1 (entries 3a-3j). The results demonstrated how broadly applicable the suggested methodology is. In terms of catalyst, temperature, reaction time, and % yields, some previously published data for the synthesis of 3a (Table 1, entry 1) were compared with our findings. As can be seen, our results in terms of yields and reaction times demonstrate a very strong comparability with previously reported data (Table 2). 3.2 Spectroscopic studies The isolated products were fully characterized on the basis of their analytical data and detailed spectral studies including FT-IR, 1H NMR, 13C NMR, and TOF-MS. All known compounds had physical and spectroscopic data identical to those reported in the literature [18-26]. The observation of a distinct absorption peak at 1695-1678 cm-1 in FT-IR spectra is consistent with the C=O stretching vibration typically associated with the carboxyl group (COOH) in organic compounds. This suggests the presence of carboxyl functional groups in the synthesized derivatives. The IR bands at 1781-1751 cm-1 support the existence of the cyclic ester group within compounds. These spectral bands are indicative of the carbonyl (C=O) stretching vibration in cyclic esters, which is characteristic of coumarin-3-carboxylic acids. The observed peak in the 1H NMR spectra (δ 12.81-8.60 ppm) aligns with the presence of -OH protons, specifically Sonawane et al. / European Journal of Chemistry 14 (4) (2023) 439-444 443 2023 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.14.4.439-444.2471 carboxyl groups, within the compounds. Variation in chemical shift within this region reflects the diverse chemical environments of these functional groups. In particular, our findings closely resemble data from the literature data (δ 12.26) associated with carboxylic –OH peaks, which confirms the identification of these groups in our compounds [19]. The 1H- NMR spectrum of compound 3j showed the signal for MeO-C at δ (H) 3.93. The two distinct signals in the range of δ (H) 6.01– 6.00 corresponded to HC (5, 7), whereas the signal for HC (4) appeared deshielded as s at δ (H) 7.15, in agreement with its β -position with respect to the CO group. The two distinct signals in the range of δ (H) 5.98–5.92 and the strongly shielded signal at δ (H) 3.42 corresponded to the allyl group (6). The 13C NMR spectrum revealed two distinct peaks at δ 168.39−163.46 ppm for the carboxyl C=O groups, and δ 163.07−156.81 ppm for the carbonyl of lactone in coumarin skeleton which was closely resemble literature [29]. The theoretical molecular masses of some derivatives are perfectly obtained in the LC mass spectrum with loss of electron pattern. M+ = 191.11 m/z for compound 3a, M+ = 261.15 m/z for compound 3b, and M+ = 225.11 m/z for compound 3e that matches with the calculated mass. In some spectra, M+Na contamination peaks also appear, M+Na = 245.14 m/z for compound 3c, M+Na = 245.14 m/z for compound 3d, M+Na = 226.12 m/z for compound 3f, M+Na = 268.77 m/z for compound 3g, 247.23 m/z for compound 3h, M+Na = 247.23 m/z for compound for 3i and M+Na = 261.21 m/z shows excessive mass in LC-ESI-MS experiments involving both organic and aqueous (H2O-based). 4. Conclusions The present study introduced a new synthetic protocol for the derivatives of coumarin-3-carboxylic acid, where the lactic acid-induced acidity provides the catalytic support for the reaction. Waste curd water has been demonstrated to work as an excellent catalyst for the reaction of dimethyl malonate with a variety of substituted benzaldehydes under ultrasonic irradiation in aqueous media. The catalyst-free condition, low reaction times, high yields, environmentally friendly condi- tions, and operational simplicity are the advantages of this protocol, achieving a green alternative to existing protocols. The prepared molecules were characterized by HR-MS, FT-IR, and NMR spectroscopy. Acknowledgements The authors thank all collaborators for their help and support in characterization and writing the present manuscript. Disclosure statement Conflict of interest: The authors declare that they have no conflict of interest. Ethical approval: All ethical guidelines have been adhered. Sample availability: Samples of the compounds are available from the author. CRediT authorship contribution statement Conceptualization: Nitin Bhaidas Sonawane, Dilip Ramsing Patil; Methodology: Nitin Bhaidas Sonawane, Jamatsing Darbarsing Rajput; Software: Jamatsing Darbarsing Rajput; Validation: Nitin Bhaidas Sonawane, Dilip Ramsing Patil; Formal Analysis: Nitin Bhaidas Sonawane; Investigation: Nitin Bhaidas Sonawane, Jamatsing Darbarsing Rajput; Resources: Nitin Bhaidas Sonawane, Dilip Ramsing Patil; Data Curation: Nitin Bhaidas Sonawane; Writing - Original Draft: Nitin Bhaidas Sonawane,; Writing - Review and Editing: Dilip Ramsing Patil, Nitin Bhaidas Sonawane; Visualization: Nitin Bhaidas Sonawane; Funding acquisition: Nitin Bhaidas Sonawane, Dilip Ramsing Patil; Supervision: Dilip Ramsing Patil, Jamatsing Darbarsing Rajput; Project Administration: Nitin Bhaidas Sonawane, Dilip Ramsing Patil. ORCID and Email Nitin Bhaidas Sonawane prof.nbsonawane@gmail.com https://orcid.org/0009-0001-0483-4649 Jamatsing Darbarsing Rajput jamatsingh50@gmail.com jamat.chem@gmail.com https://orcid.org/0000-0002-4588-1345 Dilip Ramsing Patil dr.drpatil@gmail.com https://orcid.org/0009-0000-9446-1657 References [1]. Barot, K. P.; Jain, S. V.; Kremer, L.; Singh, S.; Ghate, M. D. Recent advances and therapeutic journey of coumarins: current status and perspectives. Med. Chem. Res. 2015, 24, 2771–2798. [2]. Garg, S. S.; Gupta, J.; Sharma, S.; Sahu, D. An insight into the therapeutic applications of coumarin compounds and their mechanisms of action. Eur. J. Pharm. Sci. 2020, 152, 105424. [3]. Kamel, N. N.; Aly, H. F.; Fouad, G. I.; Abd El-Karim, S. S.; Anwar, M. M.; Syam, Y. M.; Elseginy, S. A.; Ahmed, K. A.; Booles, H. F.; Shalaby, M. B.; Khalil, W. K. B.; Sandhir, R.; Deshwal, S.; Rizk, M. Z. Anti-Alzheimer activity of new coumarin-based derivatives targeting acetylcholinesterase inhibition. 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This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at http://www.eurjchem.com/index.php/eurjchem/pages/view/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution, or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (http://www.eurjchem.com/index.php/eurjchem/pages/view/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry). http://www.eurjchem.com/index.php/eurjchem/pages/view/terms http://creativecommons.org/licenses/by-nc/4.0 http://www.eurjchem.com/index.php/eurjchem/pages/view/terms 1. Introduction 2. Experimental 2.1. Instrumentation 2.2. Materials 2.3. Procedure for the preparation of curd water solvent 2.4. General procedure for the synthesis of derivatives of coumarin-3-carboxylic acid 3. Results and discussion 3.1. Synthesis of 3-carboxycoumarin derivatives 3.2 Spectroscopic studies 4. Conclusions Acknowledgements Disclosure statement CRediT authorship contribution statement ORCID and Email References PrintField10: PrintField11: PrintField12: PrintField13: PrintField14: PrintField15: PrintField20: PrintField21: PrintField22: PrintField23: PrintField24: PrintField25: