Description:FORM 2
THE PATENTS ACT 1970
(39 of 1970)
&
The Patent Rules 2003
COMPLETE SPECIFICATION
(see sections 10 & rule 13)
1. TITLE OF THE INVENTION
“DEUTERATED AROMATIC HYDROCARBON COMPOUNDS AND METHOD FOR SYNTHESIZING THEREOF”
2. APPLICANT (S)
NAME NATIONALITY ADDRESS
CLEARSYNTH LABS LIMITED INDIAN 17th Floor, Lotus Nilkamal Business Park New Link Road, Andheri [West],
Mumbai, Maharashtra, India, 400053
3. PREAMBLE TO THE DESCRIPTION

COMPLETE SPECIFICATION
The following specification particularly describes the invention and the manner in which it is to be performed

FIELD OF INVENTION
The present invention relates to a deuterated aromatic hydrocarbon compound of formula (I). Most particularly, it relates to deuterated iodobenzene-d5 and method for synthesizing thereof. The said deuterated compound of formula (I) has wide applications in chemical and pharmaceutical industry.

BACKGROUND OF INVENTION
Synthesis of deuterium labelled organic compounds is of fast-growing interest due to the widespread application of mass spectrometry as a specific detection and investigation tool in pharmacological, chemical and environmental research.
For example, deuterated organic compounds are widely used as internal standards in pharmaceutical drug development for the investigation of samples originating from environmental, animal and human studies.
Another important application of deuterated compounds is based on the property of deuterium to form stronger bonds with other atoms compared to hydrogen which are therefore more difficult to cleave both chemically and metabolically. That means selective incorporation of deuterium at the site of initial metabolic oxidation may slow down the metabolism of a drug and could reduce the formation of unwanted metabolites.
A further consequence of blocking major metabolic pathways can be a lower clearance of the drug and hence a longer residence time and enhanced efficacy.
Therefore, the deuteration approach can potentially lead to a variety of beneficial effects, including longer duration of action, improved safety profile and reduced levels of toxic metabolites. In addition to deuterated organic molecules, also tritiums labelled compounds are widely employed for metabolic and pharmacokinetic investigations of new drug candidates.
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Studies involving the human use of drugs labeled with deuterium suggest that these compounds may offer some advantages when compared with their non-deuterated counterparts.
A further consequence of blocking major metabolic pathways can be a lower clearance of the drug and hence a longer residence time and enhanced efficacy. Therefore, the deuteration approach can potentially lead to a variety of beneficial effects, including longer duration of action, improved safety profile and reduced levels of toxic metabolites. In addition to deuterated organic molecules, also tritiums labelled compounds are widely employed for metabolic and pharmacokinetic investigations of new drug candidates.
Compared with a conventional synthesis starting from a suitable commercially available stable labelled precursor, H/D (hydrogen/deuterium) exchange (HDE) can be a cost- and time-efficient alternative approach particularly if it has to be carried out directly on the target molecule or an advanced intermediate.
Deuterated compounds may, in some cases, offer advantages over non-deuterated forms, often through alterations in clearance. Deuteration may also redirect metabolic pathways in directions that reduce toxicities. The approval of additional deuterated compounds may soon follow. Clinicians will need to be familiar with the dosing, efficacy, potential side effects, and unique metabolic profiles of these new entities.
Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs. For example, deuterated tetra-benazine, developed by Teva Pharmaceutical Ltd, is the first deuterated drug to receive Food and Drug Administration (USFDA) approval. This deuterated form of the drug tetra-benazine is indicated for the treatment of chorea associated with Huntington's disease as well as tardive dyskinesia. Ongoing clinical trials suggest that a number of other deuterated compounds are being evaluated for the treatment of human diseases and not merely as research tools.
Lau et al. describes preparation of chlorobenzene-D5 by using antimony pentachloride (SbCl5) as halogenating agent under normal temperature for 1h, but antimony pentachloride (SbCl5) price is high and experimental cost is very large (Lau, W.; Kochi, J. K. Journal of the American Chemical Society, 1986,108 (21), 6720 – 6732).
Kozhushkov et al. utilize benzene-D6 and sodium bromate in sulfuric acid catalysis. During this synthesis, reaction generates bromobenzene-d5 (Kozhushkov et al. “Organic Letters”, 2008, 10 (16), 3409–3412).
However, the sulfuric acid used in the synthesis of this method is a strong acid which is highly corrosive, and bromine is generated in the reaction process which is very dangerous to human health and environment.
Zhang et al. describes use of gold chloride as a catalyst and reacted for 24 hrs at 80°C to obtain the target product (Zhang et al, 1908). The catalyst used in this method was expensive.
In literature, iodobenzene-d5 is synthesized using benzene-d6 and expensive silver triflate catalyst. Reaction is executed in small scale only. And also silver triflate is moisture sensitive. Therefore, reaction forms impurities resulting in fewer yields.
Therefore, there is a need to design/develop deuterated iodobenzene-d5 compound to overcome the above mentioned problems associated with prior arts.
The present invention provides a novel deuterated compound of formula (I) and method for synthesizing said deuterated compounds. This requires neither a number of steps nor an expensive reagent, and thus is considerably economical and can be widely used for general-purposes.

OBJECTS OF INVENTION
Main object of the present invention is to provide deuterated aromatic hydrocarbon compound of formula (I).
Another object of the present invention is to provide deuterated aromatic hydrocarbon compound of formula (I), wherein said compound may be selected from Iodobenzene-d1, Iodobenzene-d2, Iodobenzene-d3, Iodobenzene-d4, and Iodobenzene-d5 and combinations thereof.
Another object of the present invention is to provide a method for synthesizing a deuterated compound of formula (I), which requires neither a number of steps nor an expensive reagent, and thus is considerably economical and can be widely used for general-purposes.
Another object of the present invention is to provide a method for synthesizing deuterated iodobenzene (iodobenzene-d5).
Another object of the present invention is to provide a simple, robust method for synthesizing compound of formula (I), where deuterated compound easily isolated from reaction mass.
Yet another object of the present invention is to provide deuterated iodobenzene which can be used as a marker for the study of iodine uptake in biological systems and metabolism.

SUMMARY OF INVENTION
One of the aspects of the present invention provides a method for synthesizing compound of formula (I)

Wherein
R1, R2, R3, R4, R5 are independently selected from hydrogen (H), deuterium (D);
X is a halogen selected from group consisting of fluorine (-F), chlorine (-Cl), bromine (-Br), Iodine (-I);
the method comprising the steps of:
a) making a mixture comprising one or more catalyst, a halogenating agent and optionally, a solvent at a room temperature;
b) adding an acid to the mixture obtained from step (a) at a temperature in the range of 00to 50C for a time period in the range of 2 to 4 hrs and stirring continuously for an additional 15min to 45min to obtain a reaction mixture; and
c) contacting a compound of formula (II) with the reaction mixture at a temperature in the range of 00C to 50C for a time period in the range of 1hr to 2 hr, and additionally stirring for 15min to 45min; and thereafter raising the temperature to 150C and stirring continuously for 5hr to 8 hr to obtain the compound of formula (I);
Wherein the compound of formula (I) obtained is having yield in the range of 60% to 70%, preferable 64%, purity is 99.13% (by GC), and D% is 99.3% (by Q-NMR).

Reaction scheme:

DETAILED DESCRIPTION OF THE INVENTION
For convenience, before further description of the present disclosure, certain terms employed in the specification, and examples are collected here. These definitions should be read in the light of the remainder of the disclosure and understood as by a person of skill in the art.
The terms used herein have the meanings recognized and known to those of skill in the art, however, for convenience and completeness, particular terms and their meanings are set forth below.
It must also be noted that as used herein, the singular forms "a", "an," and "the" include plural references unless the context clearly dictates otherwise. Although any systems and methods similar or equivalent to those described herein can be used in the practice or testing of embodiments of the present invention, the preferred, systems are now described.
The terms “comprise” and “comprising” are used in the inclusive, open sense, meaning that additional elements may be included. Throughout this specification, unless the context requires otherwise the word “comprise”, and variations, such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated element or step or group of element or steps but not the exclusion of any other element or step or group of element or steps.
The term “including” is used to mean “including but not limited to”. “Including” and “including but not limited to” are used interchangeably.
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 disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the disclosure, the preferred methods, and materials are now described.
Detailed embodiments of the present invention are disclosed herein, however, it is to be understood that the disclosed embodiments are merely exemplary of the invention, which may be embodied in various forms. Therefore, specific functional and structural details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present invention in virtually any appropriately detailed structure.
In the present invention certain terms are used for describing the invention. The definitions of the terms are provided below:
The term ‘compound’ or ‘aromatic hydrocarbon compounds’ or ‘Iodobenzene-d5’ or ‘compound of formula (I)’ or ‘Iodobenzene compound’ or ‘deuterated iodobenzene’ used herein refers to a deuterated analogue of aromatic hydrocarbon compounds which have improved pharmacokinetic properties when compared to the non-deuterated drug and is currently under clinical development (synthesis/clinical).
Deuterated aromatic hydrocarbon compounds including such as but is not limited to deuterated benzene, toluene, ethylbenzene, xylene, halobenzene (bromo-benzene, chlorobenzene, iodobenzene dichlorobenzene), nitrobenzene, phenol, hydroquinone, benzoic acid, salicylic acid, phthalic acid and aniline.
The term ‘compound’, ‘aromatic hydrocarbon compounds’, ‘Iodobenzene-d5’, ‘compound of formula (I)’, ‘Iodobenzene compound’ and ‘deuterated iodobenzene’ can be used interchangeably in the specification.
‘D’ and ‘d’ both refer to deuterium. ‘D’ and ‘d’ can be used interchangeably in the specification.
The term ‘mixture’ used herein refers to a physical blend of two or more substances that preserve their identities and are blended in the form of solutions, suspensions, or colloids. In the present invention it is formed by mixing of one or more catalyst, a halogenating agent and optionally, a solvent at a room temperature) together.
The term ‘reaction mixture’ used herein refers to combination of two or more elements, compounds or substances together causing reactions to be occurred. In the present invention reaction mixture is formed by adding one or more catalyst, a halogenating agent, catalyst and optionally, a solvent, at desired temperature for synthesis of compound of formula (I).
The term ‘solvent’ used herein refers to a substance that can dissolve another substance, or in which another substance is dissolved, forming a solution. The solvent used in the present invention can be polar or nonpolar solvent. The solvent includes such as but not limit to alcohols, ethers, ketones, acids, esters, acetonitrile (ACN) halogenated solvent(s) and/or deuterated form of alcohols, ethers, ketones, acids, esters, and/or deuterated halogenated solvent(s).
The term ‘catalyst’ used herein refers to a substance or chemical that enables a chemical reaction to proceed at a usually faster rate or under different conditions (as at a lower temperature) than otherwise possible. In the present invention catalyst may be selected from organic/inorganic acid. The catalyst is selected from hydrochloric acid, nitric acid, sulphuric acid, acetic acid, acetic anhydride, citric acid, succinic acid, oxalic acid etc. and/or combinations thereof.
One of the embodiments of the present invention provides a compound of formula (I) represented by

Another embodiment of the present invention provides a compound of formula (I), wherein R1, R2, R3, R4, or R5 is deuterium (D/d).
Another embodiment of the present invention provides a compound of formula (I), wherein X is a halogen selected from a group consisting of fluorine (-F), chlorine (-Cl), bromine (-Br), Iodine (-I).
Another embodiment of the present invention provides a method for synthesizing the compound of formula (I),

Wherein
R1, R2, R3, R4, R5 are independently selected from hydrogen (H), deuterium (D);
X is a halogen selected from group consisting of fluorine (-F), chlorine (-Cl), bromine (-Br), Iodine (-I);
the method comprising the steps of:
a) making a mixture comprising one or more catalyst, a halogenating agent and optionally, a solvent at a room temperature;
b) adding an acid to the mixture obtained from step (a) at a temperature in the range of 00to 50C for a time period in the range of 2 to 4 hrs and stirring continuously for additional 15min to 45min to obtain a reaction mixture; and
c) contacting a compound of formula (II) with the reaction mixture at a temperature in the range of 00C to 50C for a time period in the range of 1hr to 2 hr, and additionally stirring for 15min to 45min; and raising the temperature to 150C and stirring for 5hr to 8 hr to obtain the compound of formula (I);
Wherein the compound of formula (I) obtained is having yield in the range of 60% to 70%, preferable 64%, purity is 99.13% (by GC), and D% is 99.3% (by Q-NMR).
Reaction scheme:

In another embodiment of the present invention there is provided a method for synthesizing the compound of formula (I), wherein the R1, R2, R3, R4, R5, R6 in the compound of formula (II) are independently selected from hydrogen (H), deuterium (D), alkyl, and aryl group.
In another embodiment of the present invention there is provided a method for synthesizing the compound of formula (I), wherein the R1, R2, R3, R4, and R5 in the compound of formula (I) are independently selected from hydrogen (H), deuterium (D), alkyl, and aryl group; preferably deuterium (D); and wherein X in the compound of formula (I) is a halogen.
In an embodiment of the present invention there is provided a method for synthesizing compound of formula (I), wherein R1, R2, R3, R4 or R5 is deuterium (D); and X is Iodine (-I).
In an embodiment of the present invention there is provided a method for synthesizing compound of formula (I), wherein making a mixture comprising one or more catalyst, a halogenating agent; and optionally, a solvent is carried out at a room temperature.
In an embodiment of the present invention there is provided a method for synthesizing compound of formula (I), wherein adding an acid to the mixture obtained from step (a) at a temperature in the range of 00to 50C is carried out for 3hrs and stirring continuously for additional 30min.
In an embodiment of the present invention there is provided a method for synthesizing compound of formula (I), wherein contacting a compound of formula (II) with the reaction mixture at a temperature in the range of 00C to 50C is carried for 1.5hr and additionally stirring for 30min; and raising the temperature to 150C and stirring for 6hr.
In an embodiment of the present invention there is provided a method for synthesizing compound of formula (I), wherein one or more catalyst is organic and/or inorganic acid.
In an embodiment of the present invention there is provided a method for synthesizing compound of formula (I), wherein one or more catalyst used is selected from hydrochloric acid, nitric acid, sulphuric acid, acetic acid, acetic anhydride, citric acid, succinic acid, oxalic acid etc. and/or combinations thereof.
In most preferred embodiment of the present invention there is provided a method for synthesizing compound of formula (I), wherein one or more catalyst is acetic acid, acetic anhydride and combinations thereof.
In an embodiment of the present invention there is provided a method for synthesizing compound of formula (I), wherein the R1, R2, R3, R4, R5, R6 in the compound of formula (II) are independently selected from hydrogen (H), deuterium (D), alkyl, and aryl group; preferably deuterium (D).
In an embodiment of the present invention there is provided a method for synthesizing compound of formula (I), wherein said acid is selected from sulfuric acid, hydrochloric acid, hydrogen chloride, hydrobromic acid, hydroiodic acid, phosphoric acid, nitric acid, acetic acid, trichloroacetic acid, fluoro-acetic acid and perchloric acid.
In most preferred embodiment of the present invention there is provided a method for synthesizing compound of formula (I), wherein said acid is sulfuric acid.
In an embodiment of the present invention there is provided a method for synthesizing compound of formula (I), wherein the halogenating agent is selected from Iodine (I2), phosphorus trichloride (PCl5), phosphorus pentachloride (PCl4), thionyl chloride (SOCl2), phosphorus tribromide (PBr3), phosphorus pentabromide (PBr5), hydrobromic acid (HBr), potassium iodide (PI), phosphorus triiodide (PI3) or phosphorus pentaiodide (PI5), sodium periodate (NaIO4).
In most preferred embodiment of the present invention there is provided a method for synthesizing compound of formula (I), wherein halogenating agent is Iodine (I2), sodium periodate (NaIO4) and combinations thereof.
In another embodiment of the present invention there is provided a method for synthesizing the compound of formula (I), wherein the solvent is polar and/or non-polar solvent.
In another embodiment of the present invention there is provided a method for synthesizing the compound of formula (I), wherein the solvent is selected from the group consisting of water, C1 to C5 lower alcohol, N, N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, acetonitrile, dioxane, N-methylpyrrolidone, dichloromethane, chloroform, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether and ethylene glycol monomethyl ether, wherein the C1 to C5 lower alcohol is methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, n-pentanol, isopentanol, ethylene glycol, propylene glycol or glycerol and combinations thereof.
In an embodiment of the present invention there is provided a method for synthesizing compound of formula (I), wherein the solvent is selected from water, methanol, ethanol, normal propyl alcohol, isopropanol, n-butanol, isobutanol, tert-butyl alcohol, Amylalcohol, isoamyl alcohol, ethylene glycol, propane diols or glycerine, N,N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, acetonitrile, dichloromethane, chloroform, glycol dimethyl ether, diethylene glycol dimethyl ether and glycol mono-ethyl ether.
Most preferred embodiment of the present invention provides a method for synthesizing compound of formula (I), wherein schematic representation of said method is provide below.

The details of the present invention are provided in the examples given below to illustrate the invention only and therefore they should not be construed to limit the scope of invention.
EXAMPLES
To 100 L reactor, 25L of Acetic acid and 25L of acetic anhydride were added at a room temperature. To the reactor, 7.56 kg of iodine and 3.18 kg of sodium periodate (NaIO4) were added at room temperature. The reaction mass was cooled to 0°C to 5°C using ice. To the reaction mass 11.43kg of sulphuric acid was added drop wise for 3h at 0°C to 5°C. Then the reaction mixture was stirred at 0°C to 5°C for 30 min. To the reaction mixture, benzene-d6 (5 kg) was added using drop wise using additional funnel at 0°C to 5°C for 1.5h. The reaction mixture was stirred at 0°C to 5°C for 30 min, and then raised the temperature to 15°C and maintained at same temperature for 6h. The reaction mass was quenched by transferring the reaction mass to other 200 L reactor containing 100L of cold water at 2 to 5°C. The quenched reaction mass was stirred additionally for 30 min, then the two layers were separated. Bottom layer was Idobenzene-d5 compound. The organic layer was washed with 12.5L of 5% sodium hydroxide solution for two times. Crude compound (~10kg; Dark brown colour liquid) obtained was subjected to vacuum distillation at 80°C to 100°C. The obtained Idobenzene-d5: 8kg, yield: 64%, Purity by GC: 99.13%, D% by Q-NMR: 99.3%.
Reaction scheme:

We claim:
1. A method for synthesizing compound of formula (I)

Wherein
R1, R2, R3, R4, R5 are independently selected from hydrogen (H), deuterium (D);
X is a halogen selected from group consisting of fluorine (-F), chlorine (-Cl), bromine (-Br), Iodine (-I);
the method comprising the steps of:
a) making a mixture comprising one or more catalyst, a halogenating agent and optionally, a solvent at a room temperature;
b) adding an acid to the mixture obtained from step (a) at a temperature in the range of 00to 50C for a time period in the range of 2 to 4 hrs and stirring continuously for additional 15min to 45min to obtain a reaction mixture; and
c) contacting a compound of formula (II) with the reaction mixture at a temperature in the range of 00C to 50C for a time period in the range of 1hr to 2 hr, and additionally stirring for 15min to 45min; and raising the temperature to 150C and stirring continuously for 5hr to 8 hr to obtain the compound of formula (I);
Wherein the compound of formula (I) obtained is having yield in the range of 60% to 70%, preferable 64%, purity is 99.13% (by GC), and D% is 99.3% (by Q-NMR).
Reaction scheme:

2. The method for synthesizing compound of formula (I) as claimed in claim 1, wherein R1, R2, R3, R4 or R5 is deuterium (D); and X is Iodine (-I).
3. The method for synthesizing compound of formula (I), wherein the R1, R2, R3, R4, R5 R6 in the compound of formula (II) are independently selected from hydrogen (H), deuterium (D), alkyl, and aryl group; preferably deuterium (D).
4. The method for synthesizing compound of formula (I) as claimed in claim 1, wherein one or more catalyst is acetic acid, acetic anhydride and combinations thereof.
5. The method for synthesizing compound of formula (I) as claimed in claim 1, wherein acid is selected from sulfuric acid, hydrochloric acid, hydrogen chloride, hydrobromic acid, hydroiodic acid, phosphoric acid, nitric acid, acetic acid, trichloroacetic acid, fluoro-acetic acid and perchloric acid; preferably sulfuric acid.
6. The method for synthesizing compound of formula (I) as claimed in claim 1, wherein the halogenating agent is selected from Iodine (I2), phosphorus trichloride (PCl5), phosphorus pentachloride (PCl4), thionyl chloride (SOCl2), phosphorus tribromide (PBr3), phosphorus pentabromide (PBr5), hydrobromic acid (HBr), potassium iodide (PI), phosphorus triiodide (PI3) or phosphorus pentaiodide (PI5), sodium periodate (NaIO4); preferably Iodine (I2) and/or sodium periodate (NaIO4).
7. The method for synthesizing compound of formula (I) as claimed in claim 1, wherein the solvent is selected from water, methanol, ethanol, normal propyl alcohol, isopropanol, n-butanol, isobutanol, tert-butyl alcohol, Amylalcohol, isoamyl alcohol, ethylene glycol, propane diols or glycerine, N,N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, acetonitrile, dichloromethane, chloroform, glycol dimethyl ether, diethylene glycol dimethyl ether and glycol mono-ethyl ether and combinations thereof.
8. The method for synthesizing compound of formula (I) as claimed in claim 1, wherein adding acid to the mixture obtained from step (a) at a temperature in the range of 00to 50C is carried out for 3hrs and stirring continuously for additional 30min.
9. The method for synthesizing compound of formula (I) as claimed in claim 1, wherein contacting a compound of formula (II) with the reaction mixture at a temperature in the range of 00C to 50C is carried for 1.5hr and additionally stirring for 30min; and raising the temperature to 150C and stirring for 6hr.

Dated this: Sept 28, 2023
Vijaykumar Shivpuje
IN-PA/1096
To Agent for the Applicant(s)
The Controller of Patents,
The Patent Office, Mumbai

ABSTRACT

“DEUTERATED AROMATIC HYDROCARBON COMPOUNDS AND METHOD FOR SYNTHESIZING THEREOF”

The present invention relates to a compound of formula (I). Most particularly, it relates to deuterated Iodobenzene-d5 and method for synthesizing thereof. The said compound of formula (I) has wide application in chemical and pharmaceutical industry. The compound of formula (I) is represented by

Wherein R1, R2, R3, R4, and R5 are independently selected from Hydrogen (H), deuterium (D), alkyl, and aryl group; and
‘X’ is a halogen selected from fluorine (-F), chlorine (-Cl), bromine (-Br), and Iodine (-I).

, Claims:We claim:
1. A method for synthesizing compound of formula (I)

Wherein
R1, R2, R3, R4, R5 are independently selected from hydrogen (H), deuterium (D);
X is a halogen selected from group consisting of fluorine (-F), chlorine (-Cl), bromine (-Br), Iodine (-I);
the method comprising the steps of:
a) making a mixture comprising one or more catalyst, a halogenating agent and optionally, a solvent at a room temperature;
b) adding an acid to the mixture obtained from step (a) at a temperature in the range of 00to 50C for a time period in the range of 2 to 4 hrs and stirring continuously for additional 15min to 45min to obtain a reaction mixture; and
c) contacting a compound of formula (II) with the reaction mixture at a temperature in the range of 00C to 50C for a time period in the range of 1hr to 2 hr, and additionally stirring for 15min to 45min; and raising the temperature to 150C and stirring continuously for 5hr to 8 hr to obtain the compound of formula (I);
Wherein the compound of formula (I) obtained is having yield in the range of 60% to 70%, preferable 64%, purity is 99.13% (by GC), and D% is 99.3% (by Q-NMR).
Reaction scheme:

2. The method for synthesizing compound of formula (I) as claimed in claim 1, wherein R1, R2, R3, R4 or R5 is deuterium (D); and X is Iodine (-I).
3. The method for synthesizing compound of formula (I), wherein the R1, R2, R3, R4, R5 R6 in the compound of formula (II) are independently selected from hydrogen (H), deuterium (D), alkyl, and aryl group; preferably deuterium (D).
4. The method for synthesizing compound of formula (I) as claimed in claim 1, wherein one or more catalyst is acetic acid, acetic anhydride and combinations thereof.
5. The method for synthesizing compound of formula (I) as claimed in claim 1, wherein acid is selected from sulfuric acid, hydrochloric acid, hydrogen chloride, hydrobromic acid, hydroiodic acid, phosphoric acid, nitric acid, acetic acid, trichloroacetic acid, fluoro-acetic acid and perchloric acid; preferably sulfuric acid.
6. The method for synthesizing compound of formula (I) as claimed in claim 1, wherein the halogenating agent is selected from Iodine (I2), phosphorus trichloride (PCl5), phosphorus pentachloride (PCl4), thionyl chloride (SOCl2), phosphorus tribromide (PBr3), phosphorus pentabromide (PBr5), hydrobromic acid (HBr), potassium iodide (PI), phosphorus triiodide (PI3) or phosphorus pentaiodide (PI5), sodium periodate (NaIO4); preferably Iodine (I2) and/or sodium periodate (NaIO4).
7. The method for synthesizing compound of formula (I) as claimed in claim 1, wherein the solvent is selected from water, methanol, ethanol, normal propyl alcohol, isopropanol, n-butanol, isobutanol, tert-butyl alcohol, Amylalcohol, isoamyl alcohol, ethylene glycol, propane diols or glycerine, N,N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, acetonitrile, dichloromethane, chloroform, glycol dimethyl ether, diethylene glycol dimethyl ether and glycol mono-ethyl ether and combinations thereof.
8. The method for synthesizing compound of formula (I) as claimed in claim 1, wherein adding acid to the mixture obtained from step (a) at a temperature in the range of 00to 50C is carried out for 3hrs and stirring continuously for additional 30min.
9. The method for synthesizing compound of formula (I) as claimed in claim 1, wherein contacting a compound of formula (II) with the reaction mixture at a temperature in the range of 00C to 50C is carried for 1.5hr and additionally stirring for 30min; and raising the temperature to 150C and stirring for 6hr.