Description:FIELD OF THE INVENTION
The present invention relates to a 1-(1-benzofuran-2-yl)-3-(substituted phenyl)-prop-2-en-1-one and their antidepressant activity.
BACK GROUND OF THE INVENTION
A state characterized by lack of interest, irregular sleep patterns, tiredness, and occasionally suicidal thoughts is referred to as "major depression disorder" (MDD). It is a chronic, perhaps deadly mental illness that is commonly disregarded and improperly managed [Boukharsa, Y., Meddah, B., Tiendrebeogo, R.Y. Synthesis and antidepressant activity of 5- (benzo[b]furan-2-ylmethyl)-6- methylpyridazin-3(2H)-one derivatives. Med Chem Res. 2016, 25, 494–500, Lace, M. R., Scott, M., Thompson, T. D. Gould (2R, 6R)-hydroxynorketamine rapidly potentiates optically-evoked Schaffer collateral synaptic activity. Neuropharmacology, 2022, 214, 109153]. Up to 21% of the world's population, according to estimates, suffers from depression [Ashok Kumar, B.S., Lakshman, K., Velmurugan, C., Sridhar, S.M., Gopisetty, S. Antidepressant activity of methanolic extract of amaranthus spinosus. Basic Clin Neurosci. 2014, 5(1):11-7]. By 2025, the World Health Organization (WHO) projects that problems resulting from stress and the cardiovascular system will make it the second largest cause of mortality. Around the world, the burden of depression and other mental health issues is increasing. In May 2013, the World Health Assembly adopted a resolution calling for a comprehensive, coordinated national approach to mental illnesses. It is quite improbable that someone experiencing a major depressive episode will be able to go on with social, professional, or household activities, except very little [Schechter, L. E.; Ring, R. H.; Beyer, C. E. Innovative approaches for the development of antidepressant drugs: current and future strategies. Neuro therapeutics. 2005, 2, 590– 611.]. According to epidemiological research, nearly 2/3 of suicide victims are despondent when they take their own lives. Although the precise etiology of depression is unknown, the primary contributing elements are thought to include neurotransmitter unbalance in the brain, hereditary susceptibility, stressful situations in life, and medical issues [DeWeerdt, S. Mood disorders: the dark night. Nature 497:14–15 Friedman RA, Leon ACN (2007) Expanding the black box-depression, antidepressants, and the risk of suicide. Engl J Med. 2013, 356(23), 2343–2346]. There are various compounds containing benzofuran ring having several therapeutic effects such as amiodarone, angelicin, bergapten, nodekenetin, xanthotoxin, and usnic acid. These benzofuran compounds have a vital clinical application value and significant promise for usage in drug development in the future. These compounds have been widely employed in antiarrhythmic, dermatological, and anticancer therapy [Miao, Yu-hang; Hu, Yu-heng; Yang, Jie; Liu, Teng; Sun, Jie; Wang, Xiao-jing. Natural source, bioactivity and synthesis of benzofuran derivatives. RSC Advances. 2019, 9(47), 27510–27540, Sharma, U., Naveen, T., Maji, A., Manna, S., & Maiti, D. Palladium-Catalyzed Synthesis of Benzofurans and Coumarins from Phenols and Olefins. Angewandte Chemie. 2013, 125(48), 12901-12905]. It has been discovered that benzofuran derivatives are used in a variety of therapeutic areas like malignancy, psychotic disorders, CNS disorders associated with inflammation, diabetes, hormonal disturbances, renal failure, and cardiovascular disorders. In addition to these, benzofurans have been developed as herbicides, miticides, and arthropocide [Radadiya, A., Shah, A. Bioactive benzofuran derivatives: An insight on lead developments, radioligands and advances of the last decade, European Journal of Medicinal Chemistry, 2015, 97, 356-376, Chand, K. R., Hiremathad, A. S., Mahak, M. K., Rangappa, S. A. review on antioxidant potential of bioactive heterocycle benzofuran: Natural and synthetic derivatives. Pharmacological Reports. 2016, S173411401630127X]. A class of organic compounds known as chalcones has a wide range of pharmacological actions, including antiviral, antifungal, and analgesic characteristics. Recently, it has been found that flavonoids have antidepressant properties [Xin Sui, Y. Q., Yue Chang, R. Z., Yin-Feng Xu, L.G. Synthesis and studies on antidepressant activity of 2', 4', 6'-trihydroxychalcone derivatives. Med Chem Res. 2012, 21 (7), 1290– 1296]. A family of enzymes called monoamine oxidases (MAO) biogenic amine oxidation or inactivation is facilitated by CNS enzymes. [Tipton KF, Boyce S, O’Sullivan J, Davey GP, Healy J. Monoamine oxidases: certainties and uncertainties. Curr. Med. Chem. 2004;11(15):1965-82, Edmondson DE, Mattevi A, Binda C, Li M, Hublek F. Structure and mechanism of monoamine oxidase. Curr. Med. Chem. 2004;11(15):1983–93] Monoamine oxidase is inhibited by MAO inhibitors, which increases the availability of monoamine neurotransmitters like noradrenaline and serotonin by limiting their breakdown. Monoamine oxidase has two isoforms: MAO-A and MAO-B. The MAO-B inhibitors could be used to treat Parkinson's disease and Alzheimer's disease and MAO-A inhibitors have been used to treat depression, anxiety, and other mental illnesses. Clinically used antidepressants have a number of drawbacks and adverse effects that necessitate ongoing research into new, effective, and secure medications for the treatment of depression. [Rudorfer MV, Potter WZ. Antidepressants: a comparative review of the clinical pharmacology and therapeutic use of the “newer” verses the “older” drugs. Drugs. 1989;37:713–38] The majority of synthetic medications used to treat these illnesses have an impact on the system which increases the concentration of biogenic amines. Chalcone and its derivatives are also of growing interest in academia and industry [Tan, Q.W., He, L.Y., He, Z.W. Design, synthesis, and antidepressant/anticonvulsant activities of 3H-benzo[f]chromen chalcone derivatives. Med Chem Res. 2021, 30, 1427– 1437]. The pure chalcone isolates from various plants have undergone clinical trials for the treatment of viral infections, tumours, and CNS disorders. There is a need for chalcones of benzofuran as effective MAO-A inhibitors and to increase the antidepressant potential for management of depression.
OBJECTS OF THE INVENTION
The main object of the present invention is to provide a 1-(1-benzofuran-2-yl)-3-(substituted phenyl)-prop-2-en-1-one.
Another object of the present invention is to provide a 1-(1-benzofuran-2-yl)-3-(substituted phenyl)-prop-2-en-1-one useful as antidepressants.
Still another object of the invention is to provide a process for the preparation of 1-(1-benzofuran-2-yl)-3-(substituted phenyl)-prop-2-en-1-one.
SUMMARY OF THE INVENTION
Accordingly, the present invention provides a compound of formula A

Formula A
wherein, R1 is selected from hydrogen, nitro and halogen group.
In an embodiment of the present invention, the halogen group is selected from chloro, bromo and iodo group, preferably chloro group.
In an embodiment of the present invention the compound is selected from the group consisting of:
1-(1-benzofuran-2-yl)-3-phenylprop-2-en-1-one;
1-(1-benzofuran-2-yl)-3-(3-nitrophenyl)prop-2-en-1-one;
1-(1-benzofuran-2-yl)-3-(4-nitrophenyl)prop-2-en-1-one;
1-(1-benzofuran-2-yl)-3-(4-chlorophenyl)prop-2-en-1-one;
1-(1-benzofuran-2-yl)-3-(4-methoxyphenyl)prop-2-en-1-one;
1-(1-benzofuran-2-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-phenylprop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-(3-nitrophenyl)prop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-(4-nitrophenyl)prop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-(4-chlorophenyl)prop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-(4-methoxyphenyl)prop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-phenyl)prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-(3- nitrophenyl)prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-(4-nitrophenyl)prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-(4-chlorophenyl) prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-(4-methoxyphenyl)prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one.
In one aspect, the present invention provides a series of compounds that exhibit antidepressant activity.
The present invention also provides a process for the preparation of 1-(1-benzofuran-2-yl)-3-(substituted phenyl)-prop-2-en-1-one which comprises, stirring mixture of salicylaldehyde derivative and potassium carbonate in dry acetone at 250C for 1 h; cooling mixture at 0–50 C; adding chloroacetone dropwise; stirring reaction mixture at room temperature and refluxing; cooling solution of 1-benzofuran-2-ethanone and substituted aldehyde in methanol at 0–50C; adding aqueous NaOH and stirring at room temperature for 3 h; pouring reaction mixture on crushed ice to form precipitated solid; filtering precipitated solid after neutralization with diluted HCl; washing filtered solid several times with water and drying; recrystallizing crude product from ethanol to give 1-(1-benzofuran-2-yl)-3-(substituted phenyl)-prop-2-en-1-one.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with the first object of the present invention, the invention provides a compound of formula A

Formula A
wherein, R1 is selected from hydrogen, nitro and halogen group.
The halogen group in the compound of formula A of present invention are selected from chloro, bromo and iodo group, preferably chloro group.
Specific examples of compounds of the invention are 1-(1-benzofuran-2-yl)-3-phenylprop-2-en-1-one;
1-(1-benzofuran-2-yl)-3-(3-nitrophenyl)prop-2-en-1-one;
1-(1-benzofuran-2-yl)-3-(4-nitrophenyl)prop-2-en-1-one;
1-(1-benzofuran-2-yl)-3-(4-chlorophenyl)prop-2-en-1-one;
1-(1-benzofuran-2-yl)-3-(4-methoxyphenyl)prop-2-en-1-one;
1-(1-benzofuran-2-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-phenylprop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-(3-nitrophenyl)prop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-(4-nitrophenyl)prop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-(4-chlorophenyl)prop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-(4-methoxyphenyl)prop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-phenyl)prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-(3- nitrophenyl)prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-(4-nitrophenyl)prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-(4-chlorophenyl) prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-(4-methoxyphenyl)prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one.
The compound of formula A have potential for use as antidepressants. The present invention also provides a process for the preparation of 1-(1-benzofuran-2-yl)-3-(substituted phenyl)-prop-2-en-1-one which comprises, stirring mixture of salicylaldehyde derivative and potassium carbonate in dry acetone at 250C for 1 h; cooling mixture at 0–50 C; adding chloroacetone dropwise; stirring reaction mixture at room temperature and refluxing; cooling solution of 1-benzofuran-2-ethanone and substituted aldehyde in methanol at 0–5 0C; adding aqueous NaOH and stirring at room temperature for 3 h; pouring reaction mixture on crushed ice to form precipitated solid; filtering precipitated solid after neutralization with diluted HCl; washing filtered solid several times with water and drying; recrystallizing crude product from ethanol to give 1-(1-benzofuran-2-yl)-3-(substituted phenyl)-prop-2-en-1-one.
The general route for synthesis of 1-(1-benzofuran-2-yl)-3-(substituted phenyl)-prop-2-en-1-one are depicted in scheme 1 below –
Examples
The following examples are given by way of illustration of the present invention and therefore should not be construed to limit the scope of the present invention.
MATERIAL AND METHODS
Chemistry
All of the chemicals, medicines, and solvents used for the synthesis process were of laboratory quality purchased from SDFine/E.Merck/Loba. A small number of the reagent components for the synthesis were purchased from Alfa Aeser (United Kingdom) and Sigma Aldrich (Germany). The percentage yield was calculated of recrystallized products. Using a Thieles tube, the melting points of the compounds were ascertained in open capillaries. The melting points listed below are uncorrected and expressed in the Celsius scale (°C). Thin layer chromatography was carried out on microscopic slides (2 x 7.5 cm) coated with silica gel-G which was activated at 1100C for 30 min in order to monitor the reactions as well as to determine the identity and purity of reactants and products. The spots were visible by exposure to iodine vapours. The Rf values were determined. At the Dr. Rajendra Gode College of pharmacy Malkapur, the IR spectra of various compounds was done by using KBr pellets. Tetramethylsilane (TMS) was used as the internal standard while a 1H NMR (CDCl3) measurement was made at SAIF, Punjab University, Chandigarh utilizing a Bruker Advance-II 400 Spectrometer at 400 MHz. In CDCl3 solution 1H NMR, the chemical shifts (d) are reported in parts per million (ppm) in relation to TMS. Signal multiplicities are conveyed by the following signal types: singlet (s), doublet (d), triplet (t), quadruplet (q), wide singlet (bs), doublet of doublet (dd), and multiplet (m). At the Waters, Q-TOF ESI-MS spectrometer (USA), mass spectra (EI-MS) were captured. The Mass spectra of synthesized compounds were recorded on LCMS-ion trap Mass Spectrometer from Punjab University, Chandigarh. The UV-Visible 1800 double beam spectrophotometer from Shimadzu was used to measure the ultraviolet absorption spectra in methanol.
Synthesis of 1-(1-benzofuran-2-yl)ethan-1-one (4)
A mixture of salicylaldehyde (0.6 g, 4.97 mmol) and potassium carbonate (0.69 g, 4.97 mmol) in dry acetone (10 mL) was stirred at 25 °C for 1 h. Reaction mixture was cooled at 0–5 °C, and then chloroacetone (4 mL) was added dropwise. Reaction mixture was stirred at room temperature for ten minutes and then refluxed. Progress of the reaction was monitored by TLC. Upon completion, the reaction mixture was poured on crushed ice. The precipitated solid was filtered, washed with water, and dried. The product was crystallized from ethanol.
Yield: 80 %. mp: 116-118 ºC. Rf: 0.36 (Methanol: Toluene 1:4). IR (KBr, cm-1): 1756.67 (C=O), 1597.37 (C=C), 3078.23 (C-H). 1H NMR (DMSO, ppm): d 7.05-7.51 (m, 4H, Ar-H), 8.40 (s, 1H, C- H), 2.14 (s, 3H, methyl protons).
Synthesis of 1-(5-nitro-1-benzofuran-2- yl)ethan-1-one (5)
Yield: 73 %. mp: 135-137 ºC. Rf: 0.38 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1735.58 (C=O), 1525.56 (C=C), 3050.78 (C-H), 1356.45 (C-NO2). 1H NMR (DMSO, ppm): d 7.06-7.18 (m, 3H, Ar- H), 9.07 (s, 1H, C-H), 2.88 (s, 3H, methyl protons).
Synthesis of 1-(5-bromo-1-benzofuran-2-yl)ethan-1-one (6)
Following above procedure, a mixture of 5- bromosalicylaldehyde (1 g, 4.97 mmol) and potassium carbonate (0.69 g, 4.97 mmol) in dry acetone (10 mL) was stirred at 25 °C for 1 h. Reaction mixture was cooled at 0–5 °C, and then chloroacetone (4 mL) was added dropwise. Reaction mixture was stirred at room temperature for ten minutes and then refluxed to give the product (6).
Yield: 75 %. mp: 145-147 ºC. Rf: 0.39 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1715.76 (C=O), 1560.76 (C=C), 3090.34 (C-H), 678.98 (C-Br). 1H NMR (DMSO, ppm): d 6.45-7.05 (m, 3H, Ar-H), 8.13 (s, 1H, C-H), 2.75 (s, 3H, methyl protons).
Synthesis of 1-(1-benzofuran-2-yl)-3-(substituted phenyl)-prop-2-en-1-one
General Procedure for Synthesis of Chalcones:
A solution of 1-benzofuran-2-ethanone (4.18 mmol) and substituted aldehyde (4.18 mmol) in methanol (10 mL) was cooled at 0–5 °C and then 6 mL of aqueous NaOH (1 mol/L) was added to this solution and stirred at room temperature for 3 h. The reaction mixture was poured on crushed ice. The precipitated solid was filtered after neutralization with diluted HCl and was washed several times with water and then dried. The product was recrystallized from ethanol. 1-(1-benzofuran-2-yl)-3-phenylprop-2-en-1-one (7) Yield: 76 %. mp: 176-178 ºC. Rf: 0.43 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1756.22 (C=O), 1569.72 (C=C), 3053.72 (C-H). 1H NMR (DMSO, ppm): d 6.56-7.44 (m, 9H, Ar-H), 6.97 (d, J = 8 Hz, 1H, CO–CH), 7.05 (d, J = 8.1 Hz, 1H, CH–Ar).
1-(1-benzofuran-2-yl)-3-(3-nitrophenyl)prop-2-en-1-one (8)
Yield: 78 %. mp: 184-186 ºC. Rf: 0.63 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1745.34 (C=O), 1578.82 (C=C), 1378.45 (C-NO2), 3076.72 (C-H). 1H NMR (DMSO, ppm): d 6.54-7.34 (m, 8H, Ar- H), 6.56 (d, J = 8.3 Hz, 1H, CO–CH), 7.04 (d, J = 7.4 Hz, 1H, CH–Ar).
1-(1-benzofuran-2-yl)-3-(4-nitrophenyl)prop-2-en-1-one (9)
Yield: 76 %. mp: 185-187 ºC. Rf: 0.43 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1731.34 (C=O), 1612.12 (C=C), 1367.73 (C-NO2), 3123.82 (C-H). 1H NMR (DMSO, ppm): d 6.67-7.73 (m, 8H, Ar-H), 6.78 (d, J = 8.5 Hz, 1H, CO–CH), 7.09 (d, J = 7.1 Hz, 1H, CH–Ar).
1-(1-benzofuran-2-yl)-3-(4-chlorophenyl)prop-2-en-1-one (10)
Yield: 82 %. mp: 176-178 ºC. Rf: 0.53 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1738.54 (C=O), 1598.17 (C=C); 696.30 (C-Cl) 3076.47 (C-H). 1H NMR (DMSO, ppm): d 6.66-7.89 (m, 8H, Ar-H), 6.69 (d, J = 8.5 Hz, 1H, CO–CH), 7.89 (d, J = 7.1 Hz, 1H, CH–Ar). 13C NMR (DMSO-d6, 100 MHz) d: 111.06, 114.02, 115.56, 121.16, 131.93, 137.83, 143.86 and 146.41 (Ar), 76.73 (C–Cl), 39.91 (CH3). EI-MS: m/z [M+H]+ 283.87.
1-(1-benzofuran-2-yl)-3-(4-methoxyphenyl)prop-2-en-1-one (11)
Yield: 87 %. mp: 167-169 ºC. Rf: 0.54 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1745.54 (C=O), 1589.56 (C=C), 2967.56 (O-CH3) 3045.78 (C-H). 1H NMR (DMSO, ppm): d 6.87-7.82 (m, 8H, Ar- H), 5.89 (d, J = 8.3 Hz, 1H, CO–CH), 7.72 (d, J = 3.1 Hz, 1H, CH–Ar).
1-(1-benzofuran-2-yl)-3-(4-hydroxy-3-methoxy phenyl)prop-2-en-1-one (12)
Yield: 63 %. mp: 178-180 ºC. Rf: 0.52 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1757.51 (C=O), 1578.92 (C=C); 2924.84 (O-CH3), 3567.78 (O-H), 3056.73 (C-H) 1H NMR (DMSO, ppm): d 6.84- 7.72 (m, 7H, Ar-H), 5.71 (s, 1H, OH), 5.73 (d, J = 6.3 Hz, 1H, CO–CH), and 7.72 (d, J = 6.1 Hz, 1H, CH–Ar).
1-(5-nitro-1-benzofuran-2-yl)-3-phenylprop-2- en-1-one (13)
Yield: 78 %. mp: 145-147 ºC. Rf: 0.57 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1754.45 (C=O), 1573.87 (C=C), 1359.89 (C-NO2), 3061.43 (C-H). 1H NMR (DMSO, ppm): d 6.73-7.78 (m, 8H, Ar- H), 5.23 (d, J = 5.8 Hz, 1H, CO–CH), 6.89 (d, J = 7.1 Hz, 1H, CH–Ar).
1-(5-nitro-1-benzofuran-2-yl)-3-(3- nitrophenyl)prop-2-en-1-one (14)
Yield: 83 %. mp: 167-169 ºC. Rf: 0.52 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1756.32 (C=O), 1621.67 (C=C), 1373.76 (C-NO2), 3045.69 (C-H). 1H NMR (DMSO, ppm): d 6.72-7.73 (m, 7H, Ar- H), 5.62 (d, J = 6.3 Hz, 1H, CO–CH), 6.59 (d, J = 8.1 Hz, 1H, CH–Ar).
1-(5-nitro-1-benzofuran-2-yl)-3-(4- nitrophenyl)prop-2-en-1-one (15)
Yield: 73 %. mp: 172-174 ºC. Rf: 0.62 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1756.34 (C=O), 1647.51 (C=C), 1354.89 (C-NO2), 3073.81 (C-H). 1H NMR (DMSO, ppm): d 6.52-7.61 (m, 7H, Ar- H), 5.69 (d, J = 6.1 Hz, 1H, CO–CH), 6.81 (d, J = 7.2 Hz, 1H, CH–Ar).
1-(5-nitro-1-benzofuran-2-yl)-3-(4- chlorophenyl)prop-2-en-1-one (16)
Yield: 67 %. mp: 180-182 ºC. Rf: 0.52 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1753.11 (C=O), 1643.58 (C=C), 1487.56 (C-NO2), 2974.23 (C-H). 1H NMR (DMSO, ppm): d 6.96-8.51 (m, 7H, Ar- H), 6.98 (d, J = 6.7 Hz, 1H, CO–CH), 7.38 (d, J = 6.8 Hz, 1H, CH–Ar). 13C NMR (DMSO-d6, 100 MHz) d: 110.65, 111.09, 115.78, 116.74, 122.48, 128.89, 141.63 and 143.41 (Ar), 71.43 (C–Cl), 39.01 (CH3). EI-MS: m/z [M+H]+ 328.38.
1-(5-nitro-1-benzofuran-2-yl)-3-(4-methoxy phenyl)prop-2-en-1-one (17)
Yield: 68 %. mp: 156-158 ºC. Rf: 0.54 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1756.34 (C=O), 1643.45 (C=C), 1487.56 (C-NO2), 3074.23 (C-H), 2976.57 (O-CH3). 1H NMR (DMSO, ppm): d 6.78- 8.20 (m, 7H, Ar-H), 6.43 (d, J = 6.2 Hz, 1H, CO– CH), 7.21 (d, J = 6.1 Hz, 1H, CH–Ar).
1-(5-nitro-1-benzofuran-2-yl)-3-(4-hydroxy-3- methoxyphenyl)prop-2-en-1-one (18)
Yield: 72 %. mp: 162-164 ºC. Rf: 0.46 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1768.62 (C=O), 1642.69 (C=C), 1452.71 (C-NO2), 3041.65 (C-H), 2951.49 (O-CH3), 3554.86 (O-H). 1H NMR (DMSO, ppm): d 6.78-8.20 (m, 7H, Ar-H), 5.76 (s, 1H, OH), 6.43 (d, J = 6.2 Hz, 1H, CO–CH), 7.21 (d, J = 6.1 Hz, 1H, CH–Ar).
1-(5-bromo-1-benzofuran-2-yl)-3-phenyl)prop-2-en-1-one (19)
Yield: 68 %. mp: 145-147 ºC. Rf: 0.45 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1723.53 (C=O), 1650.45 (C=C), 640.56 (C-Br), 3083.58 (C-H). 1H NMR (DMSO, ppm): d 6.67-7.53 (m, 8H, Ar-H), 5.76 (d, J = 5.6 Hz, 1H, CO–CH), 6.89 (d, J = 6.8 Hz, 1H, CH–Ar).
1-(5-bromo-1-benzofuran-2-yl)-3-(3- nitrophenyl)prop-2-en-1-one (20)
Yield: 71 %. mp: 158-160 ºC. Rf: 0.56 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1767.57 (C=O), 1647.45 (C=C), 637.62 (C-Br), 1452.71 (C-NO2) 3032.23 (C-H). 1H NMR (DMSO, ppm): d 6.42- 7.51 (m, 7H, Ar-H), 5.82 (d, J = 5.4 Hz, 1H, CO–
CH), 6.71 (d, J = 7.8 Hz, 1H, CH–Ar).
1-(5-bromo-1-benzofuran-2-yl)-3-(4- nitrophenyl)prop-2-en-1-one (21)
Yield: 68 %. mp: 167-169 ºC. Rf: 0.56 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1767.57 (C=O), 1651.51 (C=C); 671.56 (C-Br), 1487.91 (C-NO2) 3083.58 (C-H). 1H NMR (DMSO, ppm): d 6.71- 7.41 (m, 8H, Ar-H), 5.86 (d, J = 5.4 Hz, 1H, CO– CH), 6.61 (d, J = 6.4 Hz, 1H, CH–Ar).
1-(5-bromo-1-benzofuran-2-yl)-3-(4- chlorophenyl) prop-2-en-1-one (22)
Yield: 72 %. mp: 156-158 ºC. Rf: 0.64 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1739.79 (C=O), 1544.98 (C=C), 678.94 (C-Br), 837.11 (C-Cl), 3136.25 (C-H). 1H NMR (DMSO, ppm): d 6.87- 8.93 (m, 7H, Ar-H), 6.56 (d, J = 6.2 Hz, 1H, CO– CH), and 6.67 (d, J = 6.5 Hz, 1H, CH–Ar). 13C NMR (DMSO-d6, 100 MHz) d: 114.55, 121.67, 122.56, 135.71, 146.29 and 148.32 (Ar), 77.30 (C– Cl), 40.81 (CH3). EI-MS: m/z [M+H]+ 362.72.
1-(5-bromo-1-benzofuran-2-yl)-3-(4- methoxyphenyl)prop-2-en-1-one (23)
Yield: 67 %. mp: 157-159 ºC. Rf: 0.53 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1789.43 (C=O), 1578.87 (C=C); 623.86 (C-Br), 3014.64 (C-H), 2822.15 (O-CH3); 1H NMR (DMSO, ppm): d 6.31- 8.31 (m, 7H, Ar-H), 6.43 (d, J = 5.2 Hz, 1H, CO– CH), 6.45 (d, J = 6.1 Hz, 1H, CH–Ar).
1-(5-bromo-1-benzofuran-2-yl)-3-(4-hydroxy-3- methoxyphenyl)prop-2-en-1-one (24)
Yield: 76 %. mp: 172-174 ºC. Rf: 0.63 (Methanol: Toulene 1:4). IR (KBr, cm-1): 1757.76 (C=O), 1645.64 (C=C); 677.81 (C-Br), 3056.61 (C-H), 2822.15 (O-CH3), 3589.52 (O-H). 1H NMR (DMSO, ppm): d 6.-8.31 (m, 7H, Ar-H), 5.65 (s, 1H, OH), 6.43 (d, J = 5.2 Hz, 1H, CO–CH), 6.45 (d, J = 6.1 Hz, 1H, CH–Ar).
Antidepressant activity
Pharmacological activities were carried out in accordance to the OECD [Draft OECD Guideline for The Testing of Chemicals, Test Guideline 452: Chronic Toxicity Studies. Draft Consultants Proposal V. 8. OECD TG 452 November, 2008, 1, 1-15] guidelines and the Institutional Animal Ethical Committee (IAEC) guidelines. The protocols were authorized under Sanction no. IAEC; 1336/ac/10/CPCSEA, dated 9th August, 2022 at Department of Pharmacology, Dr Rajendra Gode College of Pharamcy, Malkapur. The antidepressant activity of the compounds (7- 24) was evaluated using Forced Swimming Test (behavioral despair test). [Shelke, S. M.; Bhosale, S. H. Synthesis, antidepressant evaluation and QSAR studies of novel 2-(5H-[1,2, 4]triazino[5,6-b]indol-3- ylthio)-N-(substituted phenyl) acetamides. Bioorg. Med. Chem. Lett. 2010, 20, 4661-4664] The antidepressant activity was carried out on albino mice (20-25g) of either sex as experimental animals. Chlorgyline was used as standard drug. The synthesized compounds (100 mg/kg) and Chlorgyline (20 mg/kg) suspended in aqueous tween 80 (0.5%), were injected as intraperitonealy (i.p.) (??=6). After 1/2 hr, the mouse was dropped into the glass cylindrical container (diameter 10 cm, height 25 cm), containing approximately 20 cm of water at 25 ± 1 °C temperature. Water was replaced between every trial. Each mouse left for 6 minute at the end of the first 2 min; the animals showing initial vigorous struggling were immobile. The immobility times of each mouse were measured over the period of 4 min. Each mouse was judged immobile when it ceased struggling and remained floating motionless in the water, making only those movements necessary to keep its head above water. Conventional antidepressants decreased the immobility time in this test. Percentage decrease in immobility duration in test and standard drugs relative to controls was calculated and provided in Table 1.
Table 1. Percentage decrease in immobility duration in test and standard drugs relative to controls

Statistical analysis was performed using one-way analysis of variance (ANOVA) with Dunnett’s test. n = 6; dose = 100 mg/kg. Values are represented as mean ± S.E.M. Values are significant at ***P < 0.001, compared with control group.
The compounds (7-24) were evaluated for antidepressant activity by forced swim test (FST) in mice at dose of 100 mg/kg and compared with the standard drug Chlorgyline (20 mg/kg). The standard chorgyline reduced immobility times to 72.79% at a dose level of 20 mg/kg. In our research all the synthesized derivatives produced significant reduction in the immobility time when compared to the standard drug. Compounds 10, 16 and 22 were found to be the most potent derivatives from the series, showing percentage decrease in immobility duration 64.21, 69.85 and 67.40 respectively, while compounds 9, 20, 21, and 24 showed moderate activity.
, Claims:1. A compound of formula A

Formula A
wherein, R1 is selected from hydrogen, nitro and halogen group.
2. The compound as claimed in claim 1, wherein the compounds of formula A are:
1-(1-benzofuran-2-yl)-3-phenylprop-2-en-1-one;
1-(1-benzofuran-2-yl)-3-(3-nitrophenyl)prop-2-en-1-one;
1-(1-benzofuran-2-yl)-3-(4-nitrophenyl)prop-2-en-1-one;
1-(1-benzofuran-2-yl)-3-(4-chlorophenyl)prop-2-en-1-one;
1-(1-benzofuran-2-yl)-3-(4-methoxyphenyl)prop-2-en-1-one;
1-(1-benzofuran-2-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-phenylprop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-(3-nitrophenyl)prop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-(4-nitrophenyl)prop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-(4-chlorophenyl)prop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-(4-methoxyphenyl)prop-2-en-1-one;
1-(5-nitro-1-benzofuran-2-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-phenyl)prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-(3- nitrophenyl)prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-(4-nitrophenyl)prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-(4-chlorophenyl) prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-(4-methoxyphenyl)prop-2-en-1-one;
1-(5-bromo-1-benzofuran-2-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one.
3. The compound as claimed in claim 1, exhibit antidepressant activity.
4. A process for the preparation of 1-(1-benzofuran-2-yl)-3-(substituted phenyl)-prop-2-en-1-one, comprising:
a) stirring mixture of salicylaldehyde derivative and potassium carbonate in dry acetone at 25 0C for 1 h;
b) cooling mixture of step a) at 0–50 C;
c) adding chloroacetone dropwise;
d) stirring reaction mixture of step c) at room temperature and refluxing;
e) cooling solution of 1-benzofuran-2-ethanone and substituted aldehyde in methanol at 0–50C;
f) adding aqueous sodium hydroxide and stirring at room temperature for 3 h;
g) pouring reaction mixture of step f) on crushed ice to form precipitated solid;
h) filtering precipitated solid of step g) after neutralization with diluted HCl;
i) washing filtered solid of step h) several times with water and drying;
j) recrystallizing crude product of step i) from ethanol to give 1-(1-benzofuran-2-yl)-3-(substituted phenyl)-prop-2-en-1-one.

Dated this 21st day of August, 2023
To be signed digitally by
(Prabhakar R Sharma)
Agent for the Applicant
Patent Agent (IN/PA 4122)