COMPOSITION AND METHOD FOR THE SYNTHESIS OF AZETIDINE-2-ONE DERIVATIVES

Abstract

Disclosed herein is a composition (100) for the synthesis of 3-chloro-4-(2-hydroxyphenyl)-1-(6-nitrobenzo[d]thiazol-2-yl)azetidine-2-one (110), the composition (100) comprising a Schiff’s base (102) as a synthetic intermediate to facilitates cyclization to form azetidine ring, a 1,4 dioxane (104) serving as a reaction medium to dissolve the Schiff’s base (102), triethyl amine (106) acting as a base to promote nucleophilic substitution reaction, and chloroacetyl chloride (108) as an acetylating agent to facilitates the formation of chloroacetylated intermediate.

Specification

Description:FIELD OF DISCLOSURE
[0001] The present disclosure generally relates to the synthesis of azetidine-2-one derivatives, more specifically, relates to composition and method for the preparation of 3-chloro-4-(2-hydroxyphenyl)-1-(6-nitrobenzo[d]thiazol-2-yl) azetidine-2-one.
BACKGROUND OF THE DISCLOSURE
[0002] The heterocyclic compounds play a significant role in numerous scientific disciplines, taking from medicinal chemistry to material science due to their diverse biological activities. The versatility of heterocyclic compounds with their ability to undergo chemical reactions and form hydrogen bonds makes them ideal for molecular recognition and catalysis.
[0003] The compounds containing azetidine-2-one ring functions as key biological compounds in various therapeutic agents, especially in β-lactam antibiotics. The synthetic accessibility and prospect of structural optimization make azetidine-2-one derivatives valuable in drug discovery programs. Azetidine-2-one derivatives possess promising anticancer and anti-inflammatory properties reveal their potential applications as enzyme inhibitors.
[0004] Conventional azetidine-2-one derivatives are associated with significant drawbacks. They often lack molecular stability and selectivity for comprehensive biological applications. Many azetidine derivatives lacks the combination of electron withdrawing and donating groups, thereby influencing the metabolic stability.
[0005] Additionally, the existing derivatives often involve a single biological pathway that limits their therapeutic potential.
[0006] The present invention overcomes the several disadvantages of prior art by enhancing the pharmacological aspect of the present invention. Moreover, the present invention features electron withdrawing and donating groups which certainly enhance its antibacterial, anticancer and anti-inflammatory properties.
[0007] The present invention exhibits unique structure employing molecular stability and selectivity by offering opportunity to make hydrogen bonds by selective targeting the compound or group. The present invention is able to target the multiple biological pathways, and its easy synthetic method provides numerous advantages in therapeutic areas.
[0008] Thus, in light of the above-stated discussion, there exists a need for a composition and method for synthesis of novel azetidine-2-one derivatives.
SUMMARY OF THE DISCLOSURE
[0009] The following is a summary description of illustrative embodiments of the invention. It is provided as a preface to assist those skilled in the art to more rapidly assimilate the detailed design discussion which ensues and is not intended in any way to limit the scope of the claims which are appended hereto in order to particularly point out the invention.
[0010] According to illustrative embodiments, the present disclosure focuses on a composition and method for synthesis of novel azetidine-2-one derivatives which overcomes the above-mentioned disadvantages or provide the users with a useful or commercial choice.
[0011] An objective of the present disclosure is to provide a composition and method for the synthesis of 3-chloro-4-(2-hydroxyphenyl)-1-(6-nitrobenzo[d]thiazol-2-yl) azetidine-2-one.
[0012] Another objective of the present disclosure is to provide a composition which is well-known for having antibacterial, anti-cancer and anti-inflammatory properties.
[0013] Another objective of the present disclosure is to provide a composition with high molecular stability and selectivity.
[0014] Yet another objective of the present disclosure is to provide a method of synthesis of novel 3-chloro-4-(2-hydroxyphenyl)-1-(6-nitrobenzo[d]thiazol-2-yl) azetidine-2-one which targets multiple biological pathways.
[0015] In light of the above, in one aspect of the present disclosure, a composition and method for synthesis of azetidine-2-one derivative is disclosed herein. The composition comprises a Schiff's base as a synthetic intermediate to facilitates cyclization to form azetidine ring. The composition also includes 1,4 dioxane serves as a reaction medium to dissolve the Schiff's base. The composition also includes triethyl amine acts as a base to neutralize the acids formed during the reaction. The composition also includes chloroacetyl chloride as an acetylating agent to facilitates the formation of chloroacetylated intermediate.
[0016] In one embodiment, the Schiff's base is composed of 0.05 mol of 2-amino 6-nitro benzothiazole and 0.05 mol of 4-hydroxy benzaldehyde dissolved in ethanol.
[0017] In one embodiment, the Schiff's base further comprises a glacial acetic acid as a catalyst to catalyse and control the pH of the reaction involved in formation of the Schiff's base.
[0018] In one embodiment, the 0.015 mol of triethyl amine 106 and 0.015 mol of chloroacetyl chloride 108 added to 0.0075 mol of the Schiff's base 102.
[0019] In one embodiment, the composition of 3-chloro-4-(2-hydroxyphenyl)-1-(6-nitrobenzo[d]thiazol-2-yl) azetidine-2-one obtained in the form of crystals.
[0020] In light of the above, in one aspect of the present disclosure, a composition and method for synthesis of azetidine-2-one derivative is disclosed herein. The method comprising mixing 2-amino 6-nitro benzothiazole and 4-hydroxy benzaldehyde in the ethanol to form the reaction mixture. The method also includes adding a few drops of the glacial acetic acid to the reaction mixture. The method also includes refluxing the reaction mixture for three hours at 45°C temperature. The method also includes pouring the reaction mixture onto crushed ice. The method also includes filtering and washing the reaction mixture with ice-cold water to form the Schiff's base in the form of crystals. The method also includes adding triethyl amine and chloroacetyl chloride in the Schiff's base. The method also includes refluxing the reaction mixture for eight to ten hours. The method also includes pouring the reaction mixture onto crushed ice. The method also includes washing, filtration, drying, and recrystallizing to remove the alcohol to form 3-chloro-4-(2-hydroxyphenyl)-1-(6-nitrobenzo[d]thiazol-2-yl) azetidine-2-one.
[0021] These and other advantages will be apparent from the present application of the embodiments described herein.
[0022] The preceding is a simplified summary to provide an understanding of some embodiments of the present invention. This summary is neither an extensive nor exhaustive overview of the present invention and its various embodiments. The summary presents selected concepts of the embodiments of the present invention in a simplified form as an introduction to the more detailed description presented below. As will be appreciated, other embodiments of the present invention are possible utilizing, alone or in combination, one or more of the features set forth above or described in detail below.
[0023] These elements, together with the other aspects of the present disclosure and various features are pointed out with particularity in the claims annexed hereto and form a part of the present disclosure. For a better understanding of the present disclosure, its operating advantages, and the specified object attained by its uses, reference should be made to the accompanying drawings and descriptive matter in which there are illustrated exemplary embodiments of the present disclosure.
BRIEF DESCRIPTION OF THE DRAWINGS
[0024] To describe the technical solutions in the embodiments of the present disclosure or in the prior art more clearly, the following briefly describes the accompanying drawings required for describing the embodiments or the prior art. Apparently, the accompanying drawings in the following description merely show some embodiments of the present disclosure, and a person of ordinary skill in the art can derive other implementations from these accompanying drawings without creative efforts. All of the embodiments or the implementations shall fall within the protection scope of the present disclosure.
[0025] The advantages and features of the present disclosure will become better understood with reference to the following detailed description taken in conjunction with the accompanying drawing, in which:
[0026] FIG. 1 illustrates a block diagram of composition for the synthesis of 3-chloro-4-(2-hydroxyphenyl)-1-(6-nitrobenzo[d]thiazol-2-yl) azetidine-2-one, in accordance with an exemplary embodiment of the present disclosure; and
[0027] FIG. 2 illustrates a flow chart of a method, outlining the sequential steps for the synthesis of 3-chloro-4-(2-hydroxyphenyl)-1-(6-nitrobenzo[d]thiazol-2-yl) azetidine-2-one, in accordance with an exemplary embodiment of the present disclosure.
[0028] Like reference, numerals refer to like parts throughout the description of several views of the drawing.
[0029] The composition and method for synthesis of novel azetidine-2-one derivatives is illustrated in the accompanying drawings, which like reference letters indicate corresponding parts in the various figures. It should be noted that the accompanying figure is intended to present illustrations of exemplary embodiments of the present disclosure. This figure is not intended to limit the scope of the present disclosure. It should also be noted that the accompanying figure is not necessarily drawn to scale.
DETAILED DESCRIPTION OF THE DISCLOSURE
[0030] The following is a detailed description of embodiments of the disclosure depicted in the accompanying drawings. The embodiments are in such detail as to communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure.
[0031] In the following description, numerous specific details are set forth in order to provide a thorough understanding of the embodiments of the present disclosure. It may be apparent to one skilled in the art that embodiments of the present disclosure may be practiced without some of these specific details.
[0032] Various terms as used herein are shown below. To the extent a term is used, it should be given the broadest definition persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of filing.
[0033] The terms "a" and "an" herein do not denote a limitation of quantity, but rather denote the presence of at least one of the referenced items.
[0034] The terms "having", "comprising", "including", and variations thereof signify the presence of a component.
[0035] Referring now to FIG. 1 to FIG. 2 to describe various exemplary embodiments of the present disclosure. FIG. 1 illustrates a block diagram for the synthesis of 3-chloro-4-(2-hydroxyphenyl)-1-(6-nitrobenzo[d]thiazol-2-yl) azetidine-2-one, in accordance with an exemplary embodiment of the present disclosure.
[0036] The composition 100 may include a Schiff's base 102, 1,4 dioxane 104, triethyl amine 106, and chloroacetyl chloride 108.
[0037] The Schiff's base 102 plays a significant role in linking key functional groups. It serves as a synthetic intermediate to facilitates cyclization to form azetidine ring. The Schiff's base 102 aids in achieving structural stability and selectivity under mild conditions.
[0038] In one embodiment of the present invention, the Schiff's base 102 is composed of 0.05 mol of 2-amino 6-nitro benzothiazole 112 and 0.05 mol of 4-hydroxy benzaldehyde 114 dissolved in ethanol 116. 2-amino 6-nitro benzothiazole 112 acts as a nucleophile and 4-hydroxy benzaldehyde 114 serves an electrophilic site to proceed the reaction.
[0039] In one embodiment of the present invention, the Schiff's base 102 further comprises glacial acetic acid 118 as a catalyst to catalyse and control the pH of the reaction involved in formation of the Schiff's base 102.
[0040] In one embodiment of the present invention, the 0.015 mol of triethyl amine 106 and 0.015 mol of chloroacetyl chloride 108 added to 0.0075 mol of the Schiff's base 102.
[0041] In one embodiment of the present invention, the composition 100 of 3-chloro-4-(2-hydroxyphenyl)-1-(6-nitrobenzo[d]thiazol-2-yl) azetidine-2-one obtained in the form of crystals. The crystal form indicates the structural stability and purity which aids the chemical and biological properties.
[0001] 1,4 dioxane 104 serves as a reaction medium to dissolve the Schiff's base 102. It facilitates homogenous mixing with better reaction kinetics. 1,4 dioxane 104 possess high dielectric constant and low viscosity which is essential for solubilizing polar and non-polar compounds.
[0002] Triethyl amine 106 acts as a base to neutralise the acids formed during the reaction. It maintains the pH of the reaction mixture and promotes nucleophilic substitution reaction.
[0003] Chloroacetyl chloride 108 as an acetylating agent to facilitates the formation of chloroacetylated intermediate. It introduces the chloroacetyl group into the molecule which is crucial for the formation of azetidine ring.
[0004] FIG. 2 illustrates a flow chart of a method, outlining the sequential steps for the synthesis of 3-chloro-4-(2-hydroxyphenyl)-1-(6-nitrobenzo[d]thiazol-2-yl) azetidine-2-one, in accordance with an exemplary embodiment of the present disclosure.
[0005] At step 302, mixing 2-amino 6-nitro benzothiazole 112 and 4-hydroxy benzaldehyde 114 in ethanol 116 to form a reaction mixture.
[0006] At step 304, adding a few drops of glacial acetic acid 118 to the reaction mixture.
[0007] At step 306, refluxing the reaction mixture for three hours at 45°C temperature.
[0008] At step 308, pouring the reaction mixture onto crushed ice.
[0009] At step 310, filtering and washing the reaction mixture with ice-cold water to form the Schiff's base 102 in the form of crystals.
[0010] At step 312, adding triethyl amine 106 and chloroacetyl chloride 108 in the Schiff's base 102.
[0011] At step 314, refluxing the reaction mixture for eight to ten hours.
[0012] At step 316, pouring the reaction mixture onto crushed ice. At step 318, washing, filtration, drying, and recrystallizing the reaction mixture to remove the alcohol to form 3-chloro-4-(2-hydroxyphenyl)-1-(6-nitrobenzo[d]thiazol-2-yl) azetidine-2-one 110.
[0013] While the invention has been described in connection with what is presently considered to be the most practical and various embodiments, it will be understood that the invention is not to be limited to the disclosed embodiments, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the scope of the appended claims.
[0014] A person of ordinary skill in the art may be aware that, in combination with the examples described in the embodiments disclosed in this specification, units and algorithm steps may be implemented by electronic hardware, computer software, or a combination thereof.
[0015] The foregoing descriptions of specific embodiments of the present disclosure have been presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the present disclosure to the precise forms disclosed, and many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described to best explain the principles of the present disclosure and its practical application, and to thereby enable others skilled in the art to best utilize the present disclosure and various embodiments with various modifications as are suited to the particular use contemplated. It is understood that various omissions and substitutions of equivalents are contemplated as circumstances may suggest or render expedient, but such omissions and substitutions are intended to cover the application or implementation without departing from the scope of the present disclosure.
[0016] Disjunctive language such as the phrase "at least one of X, Y, Z," unless specifically stated otherwise, is otherwise understood with the context as used in general to present that an item, term, etc., may be either X, Y, or Z, or any combination thereof (e.g., X, Y, and/or Z). Thus, such disjunctive language is not generally intended to, and should not, imply that certain embodiments require at least one of X, at least one of Y, or at least one of Z to each be present.
[0017] In a case that no conflict occurs, the embodiments in the present disclosure and the features in the embodiments may be mutually combined. The foregoing descriptions are merely specific implementations of the present disclosure, but are not intended to limit the protection scope of the present disclosure. Any variation or replacement readily figured out by a person skilled in the art within the technical scope disclosed in the present disclosure shall fall within the protection scope of the present disclosure. Therefore, the protection scope of the present disclosure shall be subject to the protection scope of the claims.
, Claims:I/We Claim:
1. A composition (100) for the synthesis of 3-chloro-4-(2-hydroxyphenyl)-1-(6-nitrobenzo[d]thiazol-2-yl) azetidine-2-one, the composition (100) comprising:
a Schiff's base (102) as a synthetic intermediate to facilitates cyclization to form azetidine ring;
1,4 dioxane (104) serving as a reaction medium to dissolve the Schiff's base (102);
triethyl amine (106) acting as a base to neutralize the acids formed during the reaction; and
chloroacetyl chloride (108) as an acetylating agent to facilitates the formation of chloroacetylated intermediate.
2. The composition (100) as claimed in claim 1, wherein the Schiff's base (100) is composed of 0.05 mol of 2-amino 6-nitro benzothiazole (112) and 0.05 mol of 4-hydroxy benzaldehyde (114) dissolved in ethanol (116).
3. The composition (100) as claimed in claim 1, wherein the Schiff's base (102) further comprises glacial acetic acid (118) as a catalyst to catalyse and control the pH of the reaction involved in formation of the Schiff's base (102).
4. The composition (100) as claimed in claim 1, wherein the 0.015 mol of triethyl amine (106) and 0.015 mol of chloroacetyl chloride (108) added to 0.0075 mol of the Schiff's base (102).
5. The composition (100) as claimed in claim 1, wherein the composition (100) of 3-chloro-4-(2-hydroxyphenyl)-1-(6-nitrobenzo[d]thiazol-2-yl) azetidine-2-one obtained in the form of crystals.
6. A method (200) for the synthesis of 3-chloro-4-(2-hydroxyphenyl)-1-(6-nitrobenzo[d]thiazol-2-yl) azetidine-2-one, the method (400) comprising:
mixing 2-amino 6-nitro benzothiazole (112) and 4-hydroxy benzaldehyde (114) in ethanol (116) to form a reaction mixture;
adding a few drops of glacial acetic acid (118) to the reaction mixture;
refluxing the reaction mixture for three hours at 45°C temperature;
pouring the reaction mixture onto crushed ice;
filtering and washing the reaction mixture with ice-cold water to form the Schiff's base (102) in the form of crystals;
adding triethyl amine (106) and chloroacetyl chloride (108) in the Schiff's base (102);
refluxing the reaction mixture for eight to ten hours;
pouring the reaction mixture onto crushed ice; and
washing, filtration, drying, and recrystallizing the reaction mixture to remove the alcohol to form 3-chloro-4-(2-hydroxyphenyl)-1-(6-nitrobenzo[d]thiazol-2-yl) azetidine-2-one (110).

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