Composition and system for the synthesis of oxazine derivatives that confer immunity against pathogenic microorganisms

Abstract

A composition for the synthesis of oxazine derivatives to provide immunity against pathogenic microorganisms, comprising: 0.01 Mol Schiff base; 0.02 mol 2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide; and 0.01 mol N-((4-Bromophenyl)(2-hydroxynaphthalen-1-yl)methyl)-2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide.

Description

FIELD OF THE INVENTION

[0001] The present invention relates to the field of chemotherapeutic compounds. More specifically, the present invention discloses a compound composition and system for synthesizing oxazine derivatives to provide immunity against pathogenic microorganisms. BACKGROUND OF THE INVENTION

[0002] Oxazine scaffolds are characterized by their diverse synthetic, biological, and pharmacological properties. Oxazine derivatives are believed to possess remarkable medicinal and chemotherapeutic properties. This has prompted many researchers to develop new synthetic methods to prepare such central heterocyclic rings. Oxazine contains six-membered aromatic ring compounds with the general formula C3H3NO. Oxazine derivatives have played an important role in the development of heterocyclic chemistry and are also widely used in industrial organic synthesis. Elegant reviews by Tsoungas, Jesüs, Smist, and Achari focus primarily on synthetic strategies and the reactivity of oxazine derivatives. Reissig and colleagues have explored the synthetic potential of oxazine derivatives with carbohydrate moieties. Sukhorukov et al.reported a convenient method for the synthesis of 1,2-oxazines from nitroethane. Oxazines are six-membered heterocyclic compounds with one oxygen and one nitrogen atom as heteroatoms.

[0003] However, very little preliminary research has been conducted to investigate the property of oxazine derivatives to create immunity against pathogenic microorganisms.

[0004] Therefore, there is a need to develop a composition and system for synthesizing oxazine derivatives to provide immunity against pathogenic microorganisms.

[0005] The technical advances disclosed by the present invention overcome the limitations and disadvantages of existing and conventional systems and methods. SUMMARY OF THE INVENTION

[0006] The present invention relates to a composition and a system for synthesizing oxazine derivatives for immunity against pathogenic microorganisms.

[0007] An object of the present invention is the synthesis of the oxazine derivative to achieve antirheumatic, antianginal and antihypertensive effects.

[0008] Another object of the present invention is the synthesis of an oxazine derivative with cytotoxic and antiosteoclastic bone resorption activity.

[0009] Another object of the present invention is the development of efavirenz, a trifluoromethyl-1,3oxazin-2-one, a non-nucleoside reverse transcriptase inhibitor.

[0010] Another object of the present invention is to demonstrate significant activity against mutated HIV-1 strains.

[0011] The present invention discloses a composition for synthesizing oxazine derivatives for providing immunity against pathogenic microorganisms, comprising: 0.01 mol of Schiff base, 0.02 mol of 2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide and 0.01 mol of N-((4-bromophenyl)(2-hydroxynaphthalen-1-yl)methyl)-2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide.

[0012] The present invention describes a system for synthesizing oxazine derivatives to generate immunity against pathogenic microorganisms, comprising: a beaker for collecting acetophenone (0.02 mol) and thiourea (0.02 mol) in pyridine (30 ml); a first heating unit below the beaker for heating the beaker under reflux conditions for 5-7 hours to prepare a first reaction mixture, wherein the first reaction mixture is cooled in an acidic medium to undergo precipitation; a vacuum desiccator operatively connected to the heating unit and configured to obtain a Schiff base from the precipitate using an ethanol medium; wherein the Schiff base is mixed with thioglycolic acid containing traces of zinc chloride (ZnCl2) to prepare a second reaction mixture by heating under reflux for 10-12 hours, followed by cooling and filtration;a second heating unit for heating the second mixture after mixing with β-naphthol and para-bromobenzaldehyde under defined temperature conditions for a defined interval to obtain N-((4-bromophenyl)(2-hydroxynaphthalen-1-yl)methyl)-2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide; and wherein N-((4-bromophenyl)(2-hydroxynaphthalen-1-yl)methyl)-2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide is mixed and stirred with formaldehyde and acetonitrile to obtain a third reaction mixture, wherein the third reaction mixture is extracted with ethyl acetate and purified to form 3-(1-(4-bromophenyl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazin-2-carbonothioyl)-2-methyl-2-phenylthiazolidin-5-one.;

[0013] To further clarify the advantages and features of the present invention, a more detailed description of the invention will be given with reference to specific embodiments thereof, which are illustrated in the accompanying drawings. It should be noted that these drawings represent only typical embodiments of the invention and are therefore not to be considered limiting its scope. The invention will be described and explained in additional detail and in greater detail with reference to the accompanying drawings. SHORT DESCRIPTION OF THE FIGURE

[0014] These and other features, aspects, and advantages of the present invention will become more readily understood when the following detailed description is read with reference to the accompanying drawings, in which like characters represent like parts throughout. Fig. Figure 1 shows a block diagram of a system for the synthesis of oxazine derivatives for immunity against pathogenic microorganisms.

[0015] Furthermore, those skilled in the art will appreciate that the elements in the drawings are shown for convenience and may not necessarily be drawn to scale. For example, the flowcharts illustrate the method by key steps to enhance understanding of aspects of the present disclosure. Furthermore, with respect to device construction, one or more components of the device may have been represented in the drawings by conventional symbols, and the drawing may show only the specific details relevant to understanding embodiments of the present disclosure in order not to clutter the drawings with details that would be readily apparent to those skilled in the art who would benefit from the description herein. DETAILED DESCRIPTION:

[0016] To facilitate an understanding of the principles of the invention, reference will now be made to the embodiment illustrated in the drawings and described in specific language. It is to be understood, however, that no limitation on the scope of the invention is intended thereby, since such changes and further modifications of the illustrated system, and such further applications of the principles of the invention as illustrated therein, are contemplated as would normally occur to one skilled in the art to which the invention pertains.

[0017] It will be understood by one skilled in the art that the foregoing general description and the following detailed description are exemplary and explanatory of the invention and are not intended to be limiting thereof.

[0018] References in this specification to "one aspect," "another aspect," or similar language mean that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. Therefore, occurrences of the phrase "in one embodiment," "in another embodiment," and similar language throughout this specification may or may not all refer to the same embodiment.

[0019] The terms "comprises," "comprising," or other variations thereof are intended to cover non-exclusive inclusion, such that a process or method comprising a list of steps not only includes those steps, but may also include other steps not expressly listed or inherent in such process or method. Likewise, one or more devices or subsystems or elements or structures or components preceded by "comprises...a" does not preclude, without further limitation, the existence of other devices or other subsystems or other elements or other structures or other components or additional devices or additional subsystems or additional elements or additional structures or additional components.

[0020] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The system, methods, and examples provided herein are for illustrative purposes only and should not be considered limiting.

[0021] Embodiments of the present disclosure will be described in detail below with reference to the accompanying drawings.

[0022] A composition for synthesizing oxazine derivatives to provide immunity against pathogenic microorganisms, comprising: 0.01 mol of Schiff base; 0.02 mol of 2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide; and 0.01 mol of N-((4-bromophenyl)(2-hydroxynaphthalen-1-yl)methyl)-2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide. The Schiff base consists of: 0.02 mol of acetophenone;

[0023] 0.02 10 ml of thiourea; 10 ml of hydrochloric acid; and 30 ml of pyridine. The composition is dissolved in 100 ml of cold water to prepare a Schiff base. The composition of 2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide is prepared from N-(1-phenylethylidene)hydrazinecarbothioamide (0.01 mol) and 0.01 mol of thioglycolic acid containing 0.1 g of ZnCl2 in DMF.

[0024] The compound N-((4-bromophenyl)(2-hydroxynaphthalen-1-yl)methyl)-2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide is prepared by mixing 2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide (0.02 mol), β-naphthol (0.02 mol) and para-bromobenzaldehyde (0.02 mol).

[0025] Fig.1 shows a block diagram of a system (100) for synthesizing oxazine derivatives to provide immunity against pathogenic microorganisms, comprising: a beaker (102) for collecting acetophenone (0.02 mol) and thiourea (0.02 mol) in pyridine (30 ml); a first heating unit (104) placed below the beaker (102) for heating the beaker under reflux conditions for 5 to 7 hours to prepare a first reaction mixture, wherein the first reaction mixture is cooled in an acidic medium to undergo precipitation; a vacuum desiccator (106) operatively connected to the first heating unit (104) and configured to obtain a Schiff base from the precipitate through an ethanol medium; wherein the Schiff base is mixed with thioglycolic acid containing traces of zinc chloride (ZnCl2) to prepare a second reaction mixture by heating under reflux for 10 to 12 hours, followed by cooling and filtration;a second heating unit (108) for heating the second mixture after mixing with β-naphthol and para-bromobenzaldehyde under defined temperature conditions for a defined interval to obtain N-((4-bromophenyl)(2-hydroxynaphthalen-1-yl)methyl)-2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide; and wherein N-((4-bromophenyl)(2-hydroxynaphthalen-1-yl)methyl)-2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide is mixed and stirred with formaldehyde and acetonitrile to obtain a third reaction mixture, wherein the third reaction mixture is extracted with ethyl acetate and purified to form 3-(1-(4-bromophenyl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazin-2-carbonothioyl)-2-methyl-2-phenylthiazolidin-5-one.;

[0026] In one embodiment, the reaction mixture is poured into 100 ml of ice-cold water containing 10 ml of concentrated hydrochloric acid for precipitation, the precipitate is filtered off and washed successively with water, the filtrate is dried in a vacuum desiccator and recrystallized from ethanol.

[0027] In one embodiment, a stirrer (110) is arranged in the beaker to mix the second reaction mixture with crushed ice for cooling and thus to obtain a second reaction mixture after filtration and recrystallization.

[0028] In one embodiment, the first heating unit is a sand bath and the second heating unit is an oil bath, wherein the first heating unit performs the heating for a defined interval of 6-12 hours, wherein the second heating unit performs the heating in an oil bath preheated to 120 ° C for 3 hours.

[0029] In one embodiment, the third reaction mixture is heated under reflux for 6 hours with stirring to remove the solvent, and 30 ml of water is added, the contents are extracted with ethyl acetate, and the solvent is distilled off under reduced pressure to obtain a residue of 3-(1-(4-bromophenyl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazin-2-carbonothioyl)-2-methyl-2-phenylthiazolidin-5-one.

[0030] In an exemplary embodiment, the synthesis of N-(1-phenylethylidene)hydrazinecarbothioamide (Schiff base) is carried out. Acetophenone (0.02 mol) and thiourea (0.02 mol) in pyridine (30 mL) are heated to reflux on a sand bath for 6 hours. The reaction mixture is then poured into ice-cold water (100 mL) containing concentrated hydrochloric acid (10 mL). A solid begins to separate, which is allowed to settle for 1 hour. It is filtered off and washed successively with water. After drying in a vacuum desiccator, it is recrystallized from ethanol.

[0031] The Schiff base has a yield of 82%; melting point 94 °C; molecular weight: 193.27 Anal. calculated for C9H 11 N3SC, 55.93 N, 21.74 S, 16.59 found: C, 55.9 0 N, 21.7 2 S, 16.56.

[0032] Synthesis of 2-Methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide: An N-(1-phenylethylidene)hydrazinecarbothioamide (0.01 mol) and thioglycolic acid (0.01 mol) with traces of ZnCl (20.1 g) in DMF are heated under reflux for 11 h. The mixture is poured into crushed ice and stirred vigorously. After 20 min, solidification occurs, which is filtered off and washed with cold water. Recrystallization from ethanol yields the pure sample. Yield: 77%; melting point: 106°C; molecular weight: 252.35. Anal. calculated for C. 11 H 12 N2OS2C, 52.36 N, 11.10 S, 25.41 found: C, 52.3 3 N, 11. 06 S, 25. 37.

[0033] Synthesis of N-((4-Bromophenyl)(2-hydroxynaphthalen-1-yl)methyl)-2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide: A 2-Methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide (0.02 mol), β-naphthol (0.02 mol), and para-bromobenzaldehyde (0.02 mol) are heated to 120 °C in a preheated oil bath for 3 hours. After completion of the reaction, as indicated by TLC, the reaction is allowed to cool. The resulting solid is washed with ethanol to obtain the pure products. Yield: 65%; melting point: 117 °C; molecular weight: 563.53. Anal. calculated for C 28 H 23 BrN2O2S2C, 59.68 Br, 14.18 N, 4.97 S, 11.38 found: C, 59.62 Br, 14.15 N, 4.94 S, 11.35.

[0034] Synthesis of the final product 3-(1-(4-bromophenyl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazin-2-carbonothioyl)-2-methyl-2-phenylthiazolidin-5-one: An N-((4-bromophenyl)(2-hydroxynaphthalen-1-yl)methyl)-2-methyl-5-oxo-2-phenylthiazolidin-3-carbothioamide (0.01 mol) and formaldehyde (37%, 0.02 mol) are taken up in acetonitrile (20 ml). The reaction is refluxed with stirring for 6 hours. After completion of the reaction, the solvent is removed and 30 ml of water is added. The contents are extracted with ethyl acetate and the solvent is distilled off under reduced pressure. The residue obtained is purified by recrystallization from ethanol. Yield 63%; melting point 102 °C; Molecular weight: 575.54 Anal. calculated for C 29 H 23 BrN2O2S2C, 60.52 Br, 13.88 N, 4.87 S, 11.14 found: C, 60.47 Br, 13.87 N, 4.83 S, 11.10.

[0035] The drawings and the foregoing description provide examples of embodiments. Those skilled in the art will recognize that one or more of the described elements may well be combined into a single functional element. Alternatively, certain elements may be separated into multiple functional elements. Elements from one embodiment may be added to another embodiment. For example, orders of the processes described herein may be changed and are not limited to the manner described herein. Furthermore, the actions of any flowchart need not be implemented in the order shown; nor do all actions necessarily need to be performed. Also, those actions that are not dependent on other actions may be performed in parallel with the other actions. The scope of the embodiments is in no way limited by these specific examples.Numerous variations, whether explicitly stated in the specification or not, such as differences in structure, dimensions, and material use, are possible. The scope of the embodiments is at least as broad as indicated in the following claims.

[0036] Advantages, other benefits, and solutions to problems for specific embodiments have been described above. However, the advantages, benefits, solutions to problems, and any components that may result in an advantage or solution occurring or becoming more apparent are not to be construed as a critical, required, or essential feature or component of any or all of the claims. REFERENCE 100 System for the synthesis of oxazine derivatives that confer immunity against pathogenic microorganisms. 102 cups 104 First heating unit 106 Vacuum desiccator 108 Second heating unit 110 stirrers

Claims

[1] A composition for synthesizing oxazine derivatives to provide immunity against pathogenic microorganisms, comprising: 0.01 mol Schiff base; 0.02 mol 2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide; and 0.01 mol N-((4-Bromophenyl)(2-hydroxynaphthalen-1-yl)methyl)-2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide. [2] The composition of claim 1, wherein the Schiff base comprises: 0.02 mol acetophenone; 0.02 mol thiourea; 10 ml hydrochloric acid; and 30 ml pyridine. [3] A composition according to claim 2, wherein the composition is dissolved in 100 ml of cold water to prepare a Schiff base. [4] A composition according to claim 1, wherein 2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide is prepared from N-(1-phenylethylidene)hydrazinecarbothioamide (0.01 mol) and 0.01 mol of thioglycolic acid containing 0.1 g of ZnCl 2 in DMF. [5] The composition according to claim 1, wherein N-((4-bromophenyl)(2-hydroxynaphthalen-1-yl)methyl)-2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide is prepared by mixing 2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide (0.02 mol), β-naphthol (0.02 mol) and para-bromobenzaldehyde (0.02 mol). [6] A system (100) for synthesizing oxazine derivatives to provide immunity against pathogenic microorganisms, comprising: a beaker (102) for collecting acetophenone (0.02 mol) and thiourea (0.02 mol) in pyridine (30 ml); a first heating unit (104) arranged below the beaker (102) for heating the beaker under reflux conditions for 5-7 hours to prepare a first reaction mixture, wherein the first reaction mixture is cooled in an acidic medium to carry out precipitation; a vacuum desiccator (106) operatively connected to the first heating unit (104) and configured to obtain a Schiff base from the precipitate using an ethanol medium; wherein the Schiff base is mixed with thioglycolic acid containing traces of zinc chloride (ZnCl2) to prepare a second reaction mixture by heating under reflux for 10-12 hours, followed by cooling and filtration; a second heating unit (108) for heating the second mixture after mixing with β-naphthol and para-bromobenzaldehyde under defined temperature conditions for a defined interval to obtain N-((4-bromophenyl)(2-hydroxynaphthalen-1-yl)methyl)-2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide; and wherein N-((4-bromophenyl)(2-hydroxynaphthalen-1-yl)methyl)-2-methyl-5-oxo-2-phenylthiazolidine-3-carbothioamide is mixed and stirred with formaldehyde and acetonitrile to obtain a third reaction mixture, wherein the third reaction mixture is extracted with ethyl acetate and purified to form 3-(1-(4-bromophenyl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazin-2-carbonothioyl)-2-methyl-2-phenylthiazolidin-5-one. [7] The system according to claim 6, wherein the reaction mixture is poured into 100 ml of ice-cold water containing 10 ml of concentrated hydrochloric acid for precipitation, the precipitate is filtered off and washed successively with water, the filtrate is dried in a vacuum desiccator and recrystallized from ethanol. [8] The system of claim 6, wherein a stirrer (110) is arranged in the beaker to mix the second reaction mixture with crushed ice for cooling and thus obtain a second reaction mixture after filtration and recrystallization. [9] System according to claim 6, wherein the first heating unit is a sand bath and the second heating unit is an oil bath, wherein the first heating unit carries out the heating for a defined interval of 6 to 12 hours, wherein the second heating unit carries out the heating in a temperature controlled at 120 ° C preheated oil bath for 3 hours. [10] The system according to claim 6, wherein the third reaction mixture is refluxed with stirring for 6 hours to remove the solvent, and 30 ml of water is added thereto, the contents are extracted with ethyl acetate, and the solvent is distilled off under reduced pressure to obtain a residue of 3-(1-(4-bromophenyl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazin-2-carbonothioyl)-2-methyl-2-phenylthiazolidin-5-one.

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