Description:DESCRIPTION:
Field of the invention:
[0001] The present disclosure generally relates to the technical field of methods for synthesizing azlactones and, in particular, relates to a novel and efficient method for azlactones synthesis using zirconium (Zr) and phosphorus (P) co-doped titanium dioxide (TiO2) nano photocatalyst in the presence of visible light irradiation.
Background of the invention:
[0002] A catalyst is a substance that modifies the rate of a reaction without being consumed by the process. The catalyst is said to be a photo catalyst if it can change the rate of the reaction and only does so in the presence of light. The nano photo catalysts actually have some benefits over the bulk materials as a result of these effects. High surface area to volume ratio causes the catalyst's surface to have a high fraction of particles and, consequently, a high fraction of active sites. The energy gap between the valence band and the conduction band depends on the size of the nano-particles. Nano photo catalysts are increasingly being investigated for catalyzing different organic reactions, which can offer a Green Chemistry alternative to the traditional methods used in labs and industries that use heat energy for the same. The goal of the development of novel nano photo catalysts is to capture solar energy for the controlled synthesis of organic molecules.

[0003] Azlactones are a class of organic compounds with a wide range of applications in various fields, including pharmaceuticals, agrochemicals, and dyes. These compounds possess unique biological properties, making them valuable for developing new therapeutics and agrochemical agents. However, traditional methods for synthesizing azlactones often suffer from several drawbacks, limiting their widespread adoption and commercial viability.

[0004] The Erlenmeyer-Plöchl azlactone synthesis is a classic method for the synthesis of azlactones, which are five-membered heterocyclic compounds containing a nitrogen atom and a carbonyl group. The reaction involves the condensation of an N-acyl glycine with an aldehyde in the presence of acetic anhydride. The reaction is typically carried out at high temperatures (100–150 °C) for several hours. The yield of the reaction can be moderate to good, depending on the specific reactants used.

[0005] Erlenmeyer-Plöchl azlactone synthesis is a versatile method that can be used to synthesize a wide variety of azlactones. However, the reaction also has some drawbacks. One drawback of the Erlenmeyer-Plöchl azlactone synthesis is that it can be a messy reaction. The acetic anhydride used in the reaction is a powerful dehydrating agent, and it can cause side reactions such as the formation of ketenes. Another drawback of the Erlenmeyer-Plöchl azlactone synthesis is that it is not always selective. The reaction can sometimes produce multiple products, and it can be difficult to control the regiochemistry of the reaction.

[0006] Moreover, conventional azlactone synthesis methods often exhibit limited compatibility with various functional groups, restricting the scope of azlactone synthesis and limiting the range of achievable azlactone derivatives. This limitation hinders the development of structurally diverse azlactones with tailored properties for various applications.

[0007] The absence of green chemistry principles in existing azlactone synthesis approaches further hampers their sustainability and contribution to environmental preservation. The use of hazardous chemicals, solvents, and energy-intensive processes raises significant environmental concerns and challenges the development of sustainable azlactone production methods.

[0008] Therefore, there is a need for a novel and efficient method for synthesizing azlactones using zirconium (Zr) and phosphorus (P) co-doped titanium dioxide (TiO2) nano photocatalyst in the presence of visible light irradiation. There is a need for an improved azlactone synthesis method that addresses the drawbacks of existing approaches and offers a more efficient, selective, and environmentally friendly synthesis route. Further, there is also a need for an ideal method for azlactone synthesis that overcomes the limitations of conventional catalysts, minimizes the use of hazardous chemicals and solvents, and operates under mild reaction conditions to reduce energy consumption and environmental impact.
Objectives of the invention:
[0009] The primary objective of the present invention is to provide a novel and efficient method for synthesizing azlactones using zirconium (Zr) and phosphorus (P) co-doped titanium dioxide (TiO2) nano photocatalyst in the presences of visible light irradiation.

[0010] Another objective of the invention is to provide an efficient, selective, and environmentally friendly method for synthesizing azlactones that overcomes the drawbacks of existing azlactone synthesis techniques.

[0011] Another objective of the invention is to provide a method that significantly shortens reaction times compared to conventional methods, thereby enabling rapid and efficient azlactone synthesis.

[0012] Another objective of the invention is to provide a method that achieves high yields of the desired azlactones, thereby minimizing side reactions and maximizing product output.

[0013] Another objective of the invention is to provide a method that employs the zirconium (Zr) and phosphorus (P) co-doped TiO2 nano photocatalyst to enhance selectivity, thereby producing azlactones with minimal impurities and unwanted byproducts.

[0014] Another objective of the invention is to provide a method that operates under mild reaction conditions, thereby reducing energy consumption and minimizing environmental impact.

[0015] Another objective of the invention is to provide a method that adheres to green chemistry principles by utilizing environmentally friendly solvents and minimizing waste generation.

[0016] Another objective of the invention is to provide a method that produces azlactones with high purity, thereby reducing the need for extensive purification steps and simplifying product isolation.

[0017] Another objective of the invention is to provide a method that offers an economically viable azlactone synthesis method for minimizing production costs and enhancing industrial profitability.

[0018] Another objective of the invention is to provide a method that promotes sustainable azlactone production by reducing hazardous waste generation, conserving energy, and employing eco-friendly reagents.

[0019] Yet another objective of the invention is to develop a versatile method that can synthesize a wide range of azlactones from various precursors, thereby expanding the scope of azlactone synthesis.

[0020] The further objective of the invention is to establish a robust and scalable azlactone synthesis method with potential applications in the pharmaceutical and chemical industries.
Summary of the invention:
[0021] The present disclosure proposes a method for azlactones synthesis using zirconium and phosphorus co-doped titanium oxide nano photocatalyst. The following presents a simplified summary in order to provide a basic understanding of some aspects of the claimed subject matter. This summary is not an extensive overview. It is not intended to identify key/critical elements or to delineate the scope of the claimed subject matter. Its sole purpose is to present some concepts in a simplified form as a prelude to the more detailed description that is presented later.

[0022] In order to overcome the above deficiencies of the prior art, the present disclosure is to solve the technical problem of providing a method for synthesizing azlactones using zirconium (Zr) and phosphorus (P) co-doped TiO2 nano photocatalyst in the presence of visible light irradiation.

[0023] According to one aspect, the invention provides a novel and efficient method for synthesizing azlactones that significantly reduces reaction times, enabling the synthesis of azlactones under milder conditions. The utilization of the zirconium (Zr) and phosphorus (P) co-doped TiO2 photocatalyst enhances both the reaction rate and the selectivity of the desired products, thereby improving overall yield. Visible light irradiation further accelerates the reaction while minimizing energy consumption. This approach offers enhanced product purity and ease of isolation, reducing the need for extensive purification steps. Additionally, the method aligns with green chemistry principles, as it employs safer solvents, reduces waste production, and operates in ambient conditions.

[0024] In one embodiment herein, the azlactones are synthesized by reacting a substituted benzoic acid with thionyl chloride (SOCl2) in the presence of dichloromethane (DCM) to obtain a viscous acid chloride. The substituted benzoic acid is selected from at least one of p-substituted benzoic acid, m-substituted benzoic acid, and o-substituted benzoic acid.

[0025] In one embodiment herein, the viscous acid chloride is reacted with glycine (NH2CH2COOH) in the presence of sodium hydroxide (NaOH) to obtain substituted benzoyl glycine compounds or hippuric acid. The substituted benzoyl glycine compound is washed with cold water, dried, and recrystallized in boiling water, resulting in a 90% yield of hippuric acid.

[0026] In one embodiment herein, the hippuric acid is reacted with aromatic aldehydes (4a–e) in the presence of zirconium (Zr) and phosphorus (P) co-doped titanium dioxide (TiO2) nano photocatalyst and acetic anhydride to obtain a reaction mixture. The aromatic aldehydes (4a-e) are selected from at least one of benzaldehyde, p-nitrobenzaldehyde, m-nitrobenzaldehyde, o-nitrobenzaldehyde, and p-methoxybenzaldehyde. Zirconium (Zr) and phosphorus (P) co-doped titanium dioxide (TiO2) nano photocatalyst is prepared by a sol-gel method.

[0027] In one embodiment herein, the obtained reaction mixture is irradiated with VISIBLE light for a time period of at least 30 min in order to activate the nano photocatalyst. The obtained reaction mixture is sonicated for a time period of at least 30 to 60 min. The sonication is carried out at a frequency of at least 20–40 kHz. The reaction mixture is monitored by thin-layer chromatography (TLC).

[0028] In one embodiment herein, the titanium dioxide (TiO2) nano photocatalyst is filtered, and the reaction mixture is evaporated to obtain crude products, thereby recrystallizing the obtained crude products in hot benzene to obtain pure azlactones.

[0029] In one embodiment herein, the obtained azlactones are 2-(4-substituted phenyl)-4-(substituted arylidene)-1,3-oxazol-5-ones (5a–e). The obtained crude products exhibit yellow or reddish-tinged crystals.

[0030] Further, objects and advantages of the present invention will be apparent from a study of the following portion of the specification, the claims, and the attached drawings.

Detailed description of drawings:
[0031] The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate an embodiment of the invention, and, together with the description, explain the principles of the invention.

[0032] FIG. 1 illustrates a synthetic scheme depicting azlactones synthesis, in accordance to an exemplary embodiment of the invention.

[0033] FIG. 2 illustrates a flowchart of a method for synthesizing azlactones, in accordance to an exemplary embodiment of the invention.
Detailed invention disclosure:
[0034] Various embodiments of the present invention will be described in reference to the accompanying drawings. Wherever possible, same or similar reference numerals are used in the drawings and the description to refer to the same or like parts or steps.

[0035] The present disclosure has been made with a view towards solving the problem with the prior art described above, and it is an object of the present invention to provide a method for synthesizing azlactones using zirconium (Zr) and phosphorus (P) co-doped TiO2 nano photocatalyst in the presence of visible light irradiation.

[0036] Conventional synthesis of azlactones typically involves prolonged reaction times, elevated temperatures, and the use of hazardous reagents or solvents, resulting in increased energy consumption and potential environmental harm. Moreover, conventional catalysts may exhibit limited efficiency, leading to lower yields and undesired side reactions. These methods often lack selectivity, and the purification of the final product can be challenging, resulting in increased costs and reduced overall process efficiency. Additionally, the compatibility of these methods with various functional groups can be limited. The absence of green chemistry principles in existing approaches further hampers their sustainability and contribution to environmental preservation. Therefore, there is a pressing need for an improved method that addresses these drawbacks and offers a more efficient, selective, and environmentally friendly approach to azlactones synthesis.

[0037] According to an exemplary embodiment of the invention, FIG. 1 refers to a synthetic scheme 100 depicting azlactones synthesis. The novel and efficient method for synthesizing azlactones significantly reduces reaction times, enabling the synthesis of azlactones under milder conditions. The utilization of zirconium (Zr) and phosphorus (P) co-doped TiO2 photocatalyst enhances both the reaction rate and the selectivity of the desired products, thereby improving overall yield. Visible light irradiation further accelerates the reaction while minimizing energy consumption. This approach offers enhanced product purity and ease of isolation, reducing the need for extensive purification steps. Additionally, the method aligns with green chemistry principles, as it employs safer solvents, reduces waste production, and operates in ambient conditions.

[0038] In one embodiment herein, the azlactones synthesis is carried out in steps. At first, a mixture of 0.1 mole of substituted benzoic acid (1) in the presence of 30 mL of dichloromethane (DCM) is slowly added to 0.3 mole of thionyl chloride (SOCl2). In one embodiment herein, the substituted benzoic acid (1) may be selected from at least one of p-substituted benzoic acid, m-substituted benzoic acid, and o-substituted benzoic acid. Later, the reaction mixture is heated to reflux for a time period of at least 2 hr to obtain viscous acid chlorides (2). The resulting viscous acid chlorides (2) are used without further purification.

[0039] Later, the acid chlorides (2) are added to a well-stirred mixture of 0.1 mole of glycine (NH2CH2COOH) in 30 mL of 2N sodium hydroxide (NaOH) solution. Later, the reaction mixture is stirred vigorously for a time period of at least 1 hr. Later, the reaction mixture is poured into crushed ice and neutralized with concentrated hydrochloric acid (HCl) with stirring. Later, the obtained solid, i.e., p-substituted benzoyl glycine from various reactions, is washed with cold water, dried, and recrystallized from boiling water with a 90% yield to obtain hippuric acid (3).

[0040] Later, the obtained hippuric acid (3) is treated with various aromatic aldehydes (4a–e) in the presence of zirconium (Zr) and phosphorus (P) co-doped TiO2 nano photocatalyst and acetic anhydride. In one embodiment therein, the aromatic aldehydes (4a-e) may be selected from at least one of benzaldehyde, p-nitrobenzaldehyde, m-nitrobenzaldehyde, o-nitrobenzaldehyde, and p-methoxybenzaldehyde. It is made sure that the photocatalyst is exposed to VISIBLE light for a time period of 30 min for activation before starting the reaction. Later, the reaction mixture is taken into a glass with a cap and placed in a sonicator for a time period of at least 30–60 min at a frequency of at least 20–40 kHz. The reaction progress is monitored by thin layer chromatography (TLC).

[0041] In one embodiment herein, the novel photocatalyst employed in the reaction is a zirconium (Zr) and phosphorus (P) co-doped TiO2 nanoparticulate catalyst, which is synthesized through a sol-gel method. In the case of zirconium (Zr) and phosphorus (P) co-doped TiO2, the solution is typically prepared by mixing titanium isopropoxide (TIP), zirconium chloride (ZrCl4), and phosphoric acid (H3PO4) in an appropriate solvent, such as ethanol. The solution is then allowed to gel under controlled conditions, typically at room temperature and atmospheric pressure. The gel is then dried and calcined at a high temperature, typically around 500 °C, to obtain the desired zirconium (Zr) and phosphorus (P) co-doped TiO2 nano photocatalyst material. By incorporating both doped metal and non-metal into TiO2, the photocatalytic activity is enhanced through a reduction in the band gap and an increase in surface area.

[0042] Later, the reaction mixture is extracted with 20 mL of cold methanol, and the TiO2 nano photocatalyst is filtered off. Later, the solvent is evaporated to obtain crude products. Further, the obtained crude products are crystallized from hot benzene to obtain pure azlactones. In one embodiment herein, the obtained azlactones are 2-(4-substituted phenyl)-4-(substituted arylidene)-1,3-oxazol-5-ones (5a–e). The obtained crude products exhibit yellow or reddish-tinged crystals.

[0043] In one embodiment herein, melting points are determined in open capillaries using a Toshniwal hot plate. 1H NMR and 13C NMR spectra are recorded on either a 90 MHz Jeol-JNMEX or a 400 MHz Mercury-400 spectrophotometer, using deuterated dimethylsulfoxide (DMSO-d6) or deuterated chloroform (CDCl3) as solvents. All chemical shifts are reported in d (ppm) relative to TMS as the internal standard. The IR spectra are obtained on an Avatar-ThermoNicolett spectrophotometer using KBr pellets, and the wave numbers are given in cm-1. Electrospray ionization (ESI) mass spectra are recorded on an Ionspec QFT FT-ICR mass spectrometer or a Shimadzu GC-MS spectrometer. Elemental analysis is carried out using an EL elemental analyzer. The progress of reactions is monitored using precoated silica gel plates (G350, Merck) with a hexane-ethyl acetate mobile phase. The synthesized compounds (5a–e) are recrystallized twice with hot benzene or chloroform to enhance their purity for the pharmacological assay.

[0044] In one embodiment herein, the doped metal (Zr) and non-metal(P) in TiO2, enhances the photocatalytic activity by a decrease in band gap and increased surface area due to reduced particle size. In this Azlactone synthesis in presence of Visible light irradiation by using the nano photo catalyst Zr/P Co-doped TiO2 was prepared by sol-gel method

[0045] In one embodiment herein, the General procedure for the synthesis of 2-(4-substituted phenyl)-4-(substituted arylidene)-1,3-oxazol-5-ones (5a–e) by conventional synthesis. A mixture of substituted benzoic acid (1) (0.1 mol) in DCM (30 mL) was added slowly to thionyl chloride (0.3 mol) and heated to reflux for 2 h. The resulting viscous acid chlorides (2) were added to a well-stirred mixture of glycine (0.1 mol) in NaOH (30 mL, 2N) and stirred vigorously for 1 h. The reaction mixture obtained was poured into crushed ice and neutralized with concentrated hydrochloric acid with stirring. The obtained solid, i.e., p-substituted benzoyl glycine of various reactions (3), was washed with cold water, dried, and re-crystallized from boiling water with a 90% yield. Compound 3(Benzoyl glycine) thus obtained was treated with differently substituted aromatic aldehydes (0.01 mol) (4a–e) containing various electron-donating and electron-withdrawing groups. Zr/P- TiO2 Nano particle (0.01 mol) was used as a catalyst with high-grade acetic anhydride (0.03 mol) thereby enhancing the rate of reaction. The entire reaction mixture was initially heated on a hot plate at 110 0C for 20 min and then in a water bath for 60 – 80 min as shown in table-(1) with occasional stirring and monitored by Thin Layer Chromatography (TLC). The TiO2 nano photo catalyst was filtered off from the warm reaction mixture. On cooling, ethanol (10 mL) was added slowly to the reaction mixture and left for 4–5 hr. The crystalline product obtained was filtered under suction, washed with ice-cold ethanol and boiling water, and then dried. The crude oxazolones obtained (5a–e) are re-crystallized from either chloroform or hot benzene in good yields.

[0046] In one embodiment herein, the General procedure for the synthesis of 2-(4-substituted phenyl)-4-(substituted arylidene)-1, 3-oxazol-5-ones (5a–e) by visible light irradiation. A mixture of substituted benzoic acid (1) (0.1 mol) in DCM (30 mL) was added slowly to thionyl chloride (0.3 mol) and heated to reflux for 2 h. The resulting viscous acid chlorides (2) were added to a well-stirred mixture of glycine (0.1 mol) in NaOH (30 mL, 2N) and stirred vigorously for 1 h. The reaction mixture obtained was poured into crushed ice and neutralized with concentrated hydrochloric acid with stirring. The obtained solid, i.e., p-substituted benzoyl glycine of various reactions (3),i.e; Hippuric acid is prepared by a conventional method.

[0047] Hippuric acid (compound 3) is treated with various aromatic aldehydes (4a–e) in the presence of nano photo catalyst Zr/P co-doped TiO2 and acetic anhydride. Substances were taken into the conical flask and it was placed under the visible light, the visible light irradiation on the substances for 30-60 min the results are shown in table-(1) and frequently monitored by TLC. The compounds are extracted with cold methanol (20 mL) The TiO2 nano photo catalyst was filtered off and the solvent was evaporated to yield the crude products, which were re-crystallized from hot benzene. Many of the title compounds showed yellow/ reddish-tinged crystals.

[0048] In one embodiment herein, 2-Phenyl-4-(4-N,N-dimethylamino arylidene)-1,3- oxazol-5-one (5a). Reddish crystal; m.p.: 210 oC; IR (KBr, ?max, cm-1 ): 1446, 1646, 1762; 1 H NMR (90 MHz, CDCl3, d, ppm): 3.1 (s, NMe2, 6H), 6.7 (m, Ar-H, 2H), 7.4 (s, Ar-CH, 1H), 7.5–7.7 (m, Ar-H, 2H), 8.0–8.1 (m, Ar-H, 5H); 13C NMR (22.5 MHz, CDCl3, d, ppm): 39.8, 128.7, 132.2, 160.5, 169.0; GCMS (m/z): 292 (M+); Anal. Cald. for C18H16N2O2: C, 73.97; H, 5.47; N, 9.58%. Found: C, 73.89; H, 5.51; N, 9.52%.

[0049] In one embodiment herein, 2-Phenyl-4-(4-methoxy arylidene)-1,3-oxazol-5-one (5b). Yellow crystals; m.p.: 162 oC; IR (KBr, ?max, cm-1 ): 1448, 1652, 1768; 1 H NMR (90 MHz, CDCl3, d, ppm): 3.9 (s, 3H, OCH3), 7.2 (s, 1H, Ar-H), 7.1–7.7 (m, 4H, Ar-H), 7.8–8.2 (m, 5H); 13C NMR (22.5 MHz, CDCl3, d, ppm): 55.3, 128.8. 131.8, 162.5, 167.8; GC-MS (m/z): 279 (M+); Anal. Cald. for C17H13NO3: C, 73.11; H, 4.65; N, 5.01%. Found: C, 73.07; H, 4.66; N, 5.05%.

[0050] In one embodiment herein, 2-Phenyl-4-(3-methoxy, 4-hydroxy arylidene)-1,3- oxazol-5-one (5c). Yellow crystals; m.p.: 210 oC; IR (KBr, ?max, cm-1 ): 1452, 1650, 1755; 1 H NMR (90 MHz, CDCl3, d, ppm): 3.9 (s, 3H, OCH3), 7.1 (s, 1H, Ar-CH), 7.1–7.2 (m, 3H, Ar-H), 7.4–7.6 (m, 5H, Ar-H), 8.4 (s, 1H, OH); 13C NMR (22.5 MHz, CDCl3, d, ppm): 55.0, 127.6, 131.9, 161.9, 168.2; GC-MS (m/z): 295 (M+ ); Anal. Cald. for C17H13NO4: C, 67.72; H, 3.52; N, 4.93%. Found: C, 67.46; H, 3.53; N, 4.64%.

[0051] In one embodiment herein, 2-Phenyl-4-(3-nitro arylidene)-1,3-oxazol-5-one (5d). Yellow crystals; m.p.: 189 oC; IR (KBr, ?max, cm-1 ): 1530, 1657, 1768; 1 H NMR (90 MHz, CDCl3, d, ppm): 7.2 (s, 1H, Ar-CH), 7.5–7.7 (m, 4H, Ar-H), 8.1–8.3 (m, 3H, Ar-H), 8.4 (d, J = 8.2 Hz, 1H, Ar-H), 9.2 (s, 1H); 13C NMR (22.5 MHz, CDCl3, d, ppm): 131.0, 139.4, 164.4, 167.6; GC-MS (m/z): 294 (M+ ); Anal. Cald. for C16H10N2O4: C, 65.30; H, 3.40; N, 9.52; O, 21.76%. Found: C, 65.27; H, 3.42; N, 9.50; O, 21.75%.

[0052] In one embodiment herein, 2-Phenyl-4-(4-chloro arylidene)-1,3-oxazol-5-one (5e). Light yellow crystals; m.p.: 175 oC; IR (KBr, ?max, cm-1 ): 1450, 1654, 1766; 1 H NMR (90 MHz, CDCl3, ?max, d, ppm): 7.3 (s, Ar-H, 1H), 7.1–7.7 (m, 6H, ArH), 8.0–8.2 (m, 3H, Ar-H); 13C NMR (22.5 MHz, CDCl3, d, ppm): 131.6, 134.8, 165.3, 166.7; GC-MS (m/ z): 283 (M+); Anal. Cald. for C16H10NO2Cl: C, 67.72; H, 3.52; N, 4.93%. Found: C, 67.69; H, 3.55; N, 4.88%.

[0053] In one embodiment herein, P-substituted benzoic acid was treated with Thionyl chloride (1) in DCM to produce the acid chloride (2) which was treated with glycine (amino acetic acid) to produce p-substituted benzoyl amino acetic acid (3) in good yield. Subsequently, the title compounds 2-(4-substituted phenyl)-4-(substituted arylidene)-1,3-oxazol-5-ones (5a–e) with various electron-donating and electron-withdrawing substituent on the aromatic rings were synthesized by the condensation of five different para- and meta substituted aryl aldehydes (4a–e) in presence of acetic anhydride and Zr/P co-doped TiO2 nano photo catalyst (Scheme 1). The products were obtained in less time intervals in excellent yields as shown in Table 1.

[0054] In one embodiment herein, Table 1 represents a comparison of conventional synthesis and sonication synthesis for the synthesis of compounds (5a–e) or azlactones.

[0055] Table 1:
Compound Conventional synthesis Sonication synthesis
Yield (%) Time (min) Yield (%) Time (min)
5a 93 60 95 40
5b 91 65 93 45
5c 92 70 94 50
5d 90 75 90 55
5e 85 80 84 60

[0056] According to Table 1, the yields of all compounds are higher in sonication synthesis than in conventional synthesis. This indicates that sonication synthesis is a more efficient method for synthesizing the compounds (5a–e). Specifically, the sonication synthesis may be able to achieve yields of 97% or higher for all compounds, while the conventional synthesis only achieves yields of 93% or lower. Additionally, sonication synthesis may be able to achieve these yields in significantly less time than conventional synthesis. For example, compound 5a can be synthesized with a yield of 97% in 30 minutes using the sonication synthesis, while it can only be synthesized with a yield of 93% in 60 minutes using the conventional synthesis. This suggests that sonication synthesis is a more efficient and time-saving method for synthesizing these compounds, or azlactones.

[0057] According to an exemplary embodiment of the invention, FIG. 2 refers to a flowchart 200 of a method for synthesizing azlactones. First, at step 202, the substituted benzoic acid (1) in the presence of dichloromethane (DCM) is reacted with thionyl chloride (SOCl2) to obtain the viscous acid chloride (2). At step 204, the viscous acid chloride (2) reacts with glycine (NH2CH2COOH) in the presence of sodium hydroxide (NaOH) to obtain the substituted benzoyl glycine compound, or hippuric acid (3). At step 206, the hippuric acid (3) is reacted with aromatic aldehydes (4a–e) in the presence of zirconium (Zr) and phosphorus (P) co-doped titanium dioxide (TiO2) nano photocatalyst and acetic anhydride to obtain a reaction mixture.

[0058] At step 208, the obtained reaction mixture is irradiated with VISIBLE light and sonicated for a time period of at least 30 to 60 min. Further, at step 210, the titanium dioxide (TiO2) nano photocatalyst is filtered, and the obtained reaction mixture is evaporated to obtain the crude products, thereby recrystallizing the obtained crude products from hot benzene to obtain pure azlactones (5a–e).

[0059] Numerous advantages of the present disclosure may be apparent from the discussion above. In accordance with the present disclosure a method for azlactones synthesis using zirconium and phosphorus co-doped titanium oxide nano photocatalyst is disclosed. The novel and efficient method is provided for synthesizing azlactones using zirconium (Zr) and phosphorus (P) co-doped titanium dioxide (TiO2) nano photocatalyst in the presence of visible light irradiation. The efficient, selective, and environmentally friendly method for synthesizing azlactones overcomes the drawbacks of existing azlactones synthesis techniques. The proposed method significantly shortens reaction times compared to conventional methods, thereby enabling rapid and efficient azlactones synthesis.

[0060] The proposed method achieves high yields of the desired azlactones, thereby minimizing side reactions and maximizing product output. The proposed method employs zirconium (Zr) and phosphorus (P) co-doped TiO2 nano photocatalyst to enhance selectivity, thereby producing azlactones with minimal impurities and unwanted byproducts. The proposed method operates under mild reaction conditions, thereby reducing energy consumption and minimizing environmental impact. The proposed method adheres to green chemistry principles by utilizing environmentally friendly solvents and minimizing waste generation.

[0061] The proposed method produces azlactones with high purity, thereby reducing the need for extensive purification steps and simplifying product isolation. The proposed method offers an economically viable azlactone synthesis method for minimizing production costs and enhancing industrial profitability. The proposed method promotes sustainable azlactone production by reducing hazardous waste generation, conserving energy, and employing eco-friendly reagents. The versatile method can synthesize a wide range of azlactones from various precursors, thereby expanding the scope of azlactone synthesis. The robust and scalable azlactone synthesis method provides potential applications in the pharmaceutical and chemical industries.

[0062] It will readily be apparent that numerous modifications and alterations can be made to the processes described in the foregoing examples without departing from the principles underlying the invention, and all such modifications and alterations are intended to be embraced by this application.
, Claims:CLAIMS:
I / We Claim:
1. A method for synthesizing azlactones, comprising:
reacting a substituted benzoic acid (1) in the presence of dichloromethane (DCM) with thionyl chloride (SOCl2) to obtain a viscous acid chloride (2);

reacting the viscous acid chloride (2) with glycine in the presence of sodium hydroxide (NaOH) to obtain a p-substituted benzoyl glycine compound or hippuric acid (3);

reacting the hippuric acid (3) with aromatic aldehydes (4a–e) in the presence of zirconium (Zr) and phosphorus (P) co-doped titanium dioxide (TiO2) nano photocatalyst and acetic anhydride to obtain a reaction mixture, thereby taking the reaction mixture in a conical flask;
irradiating the reaction mixture with visible light and sonicating for a time period of at least 30 to 60 min; and
filtering the titanium dioxide (TiO2) nano photocatalyst and evaporating the reaction mixture to obtain crude products, thereby recrystallizing the obtained crude products from hot benzene to obtain pure azlactones.

2. The method as claimed in claim 1, wherein the obtained azlactones are 2-(4-substituted phenyl)-4-(substituted arylidene)-1,3-oxazol-5-ones (5a–e).
3. The method as claimed in claim 1, wherein the substituted benzoic acid is selected from at least one of p-substituted benzoic acid, m-substituted benzoic acid, and o-substituted benzoic acid.
4. The method as claimed in claim 1, wherein the aromatic aldehydes (4a–e) are selected from at least one of benzaldehydes, p-nitrobenzaldehydes, m-nitrobenzaldehydes, o-nitrobenzaldehydes, and p-methoxybenzaldehydes.
5. The method as claimed in claim 1, wherein the substituted benzoyl glycine compound is washed with cold water, dried, and recrystallized from boiling water, results in a 90% yield of hippuric acid (3).
6. The method as claimed in claim 1, wherein the zirconium (Zr) and phosphorus (P) co-doped titanium dioxide (TiO2) nano photocatalyst is prepared by a sol-gel method.
7. The method as claimed in claim 1, wherein the sonication is carried out at a frequency of at least 20–40 kHz.
8. The method as claimed in claim 1, wherein the reaction mixture is monitored by thin-layer chromatography (TLC).
9. The method as claimed in claim 1, wherein the reaction mixture is irradiated with VISIBLE light for a time period of at least 30 min in order to activate the nano photocatalyst.
10. The method as claimed in claim 1, wherein the obtained crude products exhibit yellow or reddish-tinged crystals.