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Title:
AN IMPROVED METHOD FOR THE PREPARATION OF ALKYLENEDIOXYBENZENE COMPOUNDS
Document Type and Number:
WIPO Patent Application WO/2017/158404
Kind Code:
A1
Abstract:
This invention relates to an improved method for preparing alkylenedioxybenzene compounds of Formula I, from the corresponding ortho-dihydroxy aromatic compound of Formula II wherein n is 0, 1, 2 or 3; and R1 and R2 independently represent H, linear or branched C1 – C10 alkyl or alkenyl group, cycloalkyl group, halogen selected from C1, Br, I, nitro (-NO2), alkoxy (-OR) or SR thioether (-SR), wherein R is linear or branched alkyl group comprising C1-C6 carbon atoms.

Inventors:
MOHAPATRA MANOJ KUMAR (IN)
BENDAPUDI RAMAMOHANRAO (IN)
MENACHERRY PAUL VINCENT (IN)
PAUL VINCENT (IN)
Application Number:
PCT/IB2016/052563
Publication Date:
September 21, 2017
Filing Date:
May 05, 2016
Export Citation:
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Assignee:
ANTHEA AROMATICS PRIVATE LTD (IN)
International Classes:
C07D317/50; C07D319/18; C07D321/10
Foreign References:
US4082774A1978-04-04
US3436403A1969-04-01
Attorney, Agent or Firm:
KHURANA & KHURANA, ADVOCATES & IP ATTORNEYS (IN)
Download PDF:
Claims:
We Claim:

1. A process for the preparation of compound of Formula I

Formula I wherein n is 0, 1, 2 or 3; and Ri and R2 independently represent H, linear or branched Ci - Cio alkyl or alkenyl group, cycloalkyl group, halogen selected from CI, Br, I, nitro (-N02), alkoxy (-OR) or thioether (-SR) wherein R is selected from linear or branched alkyl group comprising C1-C6 carbon atoms, comprising the steps; i. preparing a composite solvent mixture comprising alkyl ene dihalide of Formula ΠΙ and aprotic solvent, and maintaining said composite solvent mixture at temperature between about 60°C to about 100 °C;

Formula III

wherein X is halogen selected from CI, Br, I and the like, and n and Ri are as defined hereinabove in compound of Formula I

ii. addition of ortho-dihydroxy aromatic compound of Formula II and alkali to the said component solvent mixture of step i;

Formula II

wherein R2 is as defined hereinabove in compound of Formula I

iii. contacting starting material of Formula II with alkali and alkylene dihalide compound of Formula III in said component solvent mixture maintained at the said temperature of step i;

iv. separating the compound of Formula I and the unreacted alkylene dihalide from the reaction mixture of step iii;

v. purification of the compound of Formula I by distillation.

2. The process of claim 1 wherein the component solvent mixture comprises alkylene dihalide of Formula III and aprotic solvent, wherein alkylene dihalide of Formula I in excess of stoichometric quantity by about 0.5 to about 3.0.

3. The process of claim 1 wherein the aprotic solvent is selected from the group comprising N,N-dimethylformamide, Ν,Ν-dimethylacetamide, acetonitrile, propionitrile and the like, nitrobenzene, benzonitrile, nitrtrotoluene, dimethylsulfone, tetrahydrofuran, sulfolane, dimethyl sulfoxide (DMSO) or mixtures thereof.

4. The process of claim 3 wherein the aprotic solvent is dimethyl sulfoxide.

5. The process of claim 1 wherein alkali is selected from the group comprising alkali metal hydroxide or alkali metal carbonate or alkali metal bicarbonate or mixtures thereof.

6. The process of claim 5 wherein the alkali is sodium hydroxide.

7. The process of claim 1 wherein the target compound of Formula I formed along with the unreacted alkylene dihalide of Formula III is separated from the aprotic solvent by addition of water, and azeotropic distillation using a Dean-Stark arrangement.

8. The process of claim 1 wherein compound of Formula I is represented by compound of Formula IA.

Formula IA

The process of claim 1 wherein compound of Formula I is represented by compound of Formula IB.

Formula IB

' The process of claim 1 wherein compound of Formula I is represented by compound of Formula IC.

Formula IC

The process of claim 1 wherein compound of Formula I is represented by compound of Formula ID.

Formula ID

AMENDED CLAIMS

received by the International Bureau on 04 July 2017 (04.07.2017)

1. A process for the preparation of compound of Formula I

Formula I wherein n is 0, 1, 2 or 3; and Ri and R2 independently represent H, linear or branched Ci - C10 alkyl or alkenyl group, cycloalkyl group, halogen selected from CI, Br, I, nitro (-NO2), alkoxy (-OR) or thioether (-SR) wherein R is selected from linear or branched alkyl group comprising C1-C6 carbon atoms, comprising the steps of; i. preparing a composite solvent mixture comprising alkylene dihalide of Formula III and at least one aprotic solvent, and maintaining said composite solvent mixture at a temperature ranging between about 60°C to about 100 °C;

Formula III

wherein X is halogen selected from CI, Br and I, and n and Ri are as defined with respect to the compound of Formula I;

ii. effecting addition of ortho-dihydroxy aromatic compound of Formula II and an alkali to said composite solvent mixture of step i, maintaining temperature of the reaction mixture between about 60°C to about 100 °C;

Formula II

wherein R2 is as defined with respect to the compound of Formula I; iii. separating the compound of Formula I and any unreacted alkylene dihalide from the reaction mixture of step ii; and

iv. effecting purification of the compound of Formula I.

2. The process as claimed in claim 1, wherein the composite solvent mixture comprises alkylene dihalide of Formula III in excess of stoichiometric quantity by about 0.5 to about 3.0.

3. The process as claimed in claim 1, wherein the at least one aprotic solvent is selected from a group comprising Ν,Ν-dimethylformamide, N,N-dimethylacetamide, acetonitrile, propionitrile, nitrobenzene, benzonitrile, nitrtrotoluene, dimethylsulfone, tetrahydrofuran, sulfolane, dimethyl sulfoxide (DMSO) and mixtures thereof.

4. The process as claimed in claim 3, wherein the at least one aprotic solvent is dimethyl sulfoxide.

5. The process as claimed in claim 1, wherein the alkali is selected from a group comprising alkali metal hydroxide, alkali metal carbonate, alkali metal bicarbonate and mixtures thereof.

6. The process as claimed in claim 5, wherein the alkali is sodium hydroxide.

7. The process as claimed in claim 1, wherein the target compound of Formula I formed along with any unreacted alkylene dihalide of Formula III is separated from the aprotic solvent by addition of water, and azeotropic distillation using a Dean-Stark arrangement.

8. The process as claimed in claim 1, wherein the compound of Formula I is represented by compound of Formula IA.

Formula IA

9. The process as claimed in claim 1, wherein the compound of Formula I is represented by compound of Formula IB.

Formula IB

The process as claimed in claim 1, wherein the compound of Formula I represented by compound of Formula IC.

Formula IC

11. The process as claimed in claim 1, wherein the compound of Formula I is represented by compound of Formula ID.

Formula ID

Description:
AN IMPROVED METHOD FOR THE PREPARATION OF

ALKYLENEDIOXYBENZENE COMPOUNDS

FIELD OF TECHNOLOGY:

This invention relates to an improved method for preparing alkylenedioxybenzene compounds of Formula I, from the corresponding ortho-dihydroxy aromatic compound of Formula II,

Formula I Formula II wherein n is 0, 1, 2 or 3; and Ri and R 2 independently represent H, linear or branched Ci - Cio alkyl or alkenyl group, cycloalkyl group, halogen selected from CI, Br, I, nitro (-N0 2 ), alkoxy (- OR) or thioether (-SR) wherein R is selected from linear or branched alkyl group comprising Cl- C6 carbon atoms; comprising contacting the said ortho-dihydroxy aromatic compound of Formula II with alkylene dihalide of Formula III in the presence of a base,

Formula III wherein X is halogen selected from CI, Br, I and the like, and n and Ri are as defined hereinabove The alkylenedioxybenzene compounds of Formula I are used as raw materials / intermediates in the preparation of specialty chemicals used in the pharmaceutical, agrochemical, flavor and fragrance and other industries.

The present invention relates to an efficient, industrially safe and economically viable process for preparing alkylenedioxybenzene compounds of Formula I from the corresponding compounds of Formula II comprising contacting the said compound of Formula II with alkylene dihalide compound of Formula III and a suitable alkali also referred as base, wherein the alkylene dihalide compound of Formula III is taken in excess of stoichiometric quantity along with a suitable aprotic solvent, and the excess alkylene dihalide compound plus aprotic solvent together constitute a composite solvent, and wherein the said component solvent enables the reaction medium to be maintained in the preferred temperature range of about 60 ° C to about 100 ° C to give the required compound of Formula I in high yield and purity greater than 99%.

The present invention is characterized by the use of a composite solvent to enable completion of the reaction at lower temperatures, the addition of ortho-dihydroxy aromatic compound of Formula II and a suitable alkali to the said composite solvent such that the ortho-dihydroxy aromatic compound of Formula II is substantially reacted at a rate faster than the addition rate, an efficient method of separation and recovery of solvents, and improved method for isolation of the alkylenedioxybenzene compounds of Formula I in high purity and yield, thereby providing an economical, industrially viable process for the manufacture of compounds of Formula I.

In particular,

when n is 0, and Ri and R 2 are hydrogen; the corresponding compound of Formula I is methylenedioxybenzene as shown in Formula IA.

Formula IA when n is 1, and Ri and R 2 are hydrogen; the corresponding compound of Formula I is dimethylenedioxy benzene or ethylenedioxybenzene as shown in Formula IB.

Formula IB when n is 2, and Ri and R 2 are hydrogen; the corresponding compound of Formula I is propylenedioxybenzene, also known as trimethylenedioxybenzene or propylenedioxy as shown in Formula IC.

Formula IC when n is 0, Ri is H and R 2 is -CH 3 (methyl); the corresponding compound of Formula I is 5- methyl-l,3-benzodioxole as shown in Formula ID.

Formula ID when n is 0, Ri is H and R 2 is -C3H7 (propyl); the corresponding compound of Formula I is dihydrosafrole as shown in Formula IE.

Formula IE BACKGROUND OF THE PRESENT INVENTION:

There are various chemical methods disclosed in the prior art for the synthesis of alkylenedioxybenzene compounds of Formula I.

US3436403 discloses a method for the preparation of methylenedioxybenzene comprising reactingortho-dihydroxy aromatic compound of Formula II with methylene dichloride in the presence of aprotic solvent to increase the rate of reaction and to maintain a high dilution of ions derived from dihydroxy aromatic compound thereby increasing yield of product. As per this patent, catechol is added to methylene dichloride in an aprotic solvent such as dimethyl sulfoxide (DMSO) followed by the addition of powdered sodium hydroxide and carrying out reaction in the preferred temperature range of 110 °C to 140 °C and the product of Formula I was collected by steam distillation, followed by extraction in a solvent and purification by distillation in reported yields of 46% to 91% with no mention of purity.

JP03275683 discloses a process wherein solid caustic alkali is dissolved in an aprotic solvent such as dimethyl sulfoxide under heating, and a mixed solution of catechol dissolved in an aprotic solvent and a methylene halide is dripped into the solution to give the objective compound of Formula I. The ratio in the reaction is preferably 2.1 mol caustic alkali and 1.1 to 1.5 moles of methylene chloride per mole of catechol and the reported yield is 92% without any indication of purity.

CN1180073 discloses a process for preparing methylenedioxybenzene product of Formula I comprising using catechol as raw material; wherein dichloromethane and dimethyl sulfoxide are first mixed in a ratio of 1 :4, to which is added catechol dissolved in DMSO at a temperature of 53 ° C to 90 ° C, followed by further heating at 85 ° C to 92 ° C, however the said patent does not mention the purity of the finished product so obtained.

CN1907980 discloses a process for preparing methylenedioxybenzene product of Formula I comprising taking 1.6 kg of sodium hydroxide dissolved in 3.85 kg dimethyl sulfoxidein the reactor, then adding 1.4 kg dichloromethane under stirring and adding; catechol 1.6 kg dissolved in 1.65 kg dimethyl sulfoxide under heating. When the temperature reaches to the 90 ° C, catechol solution is slowly added into the reactor, and temperature in the reactor is controlled at 90 ° C to 110 ° C for about 2.5 hours. The reported yield is 95%, however there is no mention of purityof the finished product and also the method prescribes the use of large excess of DMSO.

US2698329 discloses aprocess for the preparation of trimethylenedioxyaryl compounds, particularly trimethylenedioxybenzene, comprising reacting a trimethylene halide such as trimethylene bromide or trimethylene chloride, with the corresponding ortho-dihydroxyaryl compound in the presence of an alkaline material such as sodium methylate. The reported yield of trimethylenedioxybenzene is ~ 27% with no mention of purity.

US2007/0027184A1 discloses a method for preparation of trimethylenedioxybenzene (3,4- Dihydro-2H-benzo [l,4]dioxepine), comprising adding potassium carbonate and 1,3- dibromopropane to a solution of catechol in DMF. The reported yield of the target compound is 91% with no mention of purity. The ratio of aprotic solvent to catechol used is 15: 1.

The processes disclosed in the prior art and described hereinabove have disclosed methods for the preparation of the title compounds of Formula lfrom the corresponding ortho-dihydroxy aromatic compound of Formula II comprising contacting the said compound of Formula II with alkylene dihalide and alkali in an aprotic solvent such as dimethyl sulfoxide (DMSO) or dimethyl formamide (DMF) to speed up the reaction.

However, the methods disclosed in the prior art have typically required a large excess of aprotic solvent, typically greater than 6 moles of aprotic solvent per mole of the ortho-dihdroxy aromatic compound, leading to higher usage and cost of recovery of solvent.

Whereas the processes disclosed in the prior art have reported high yields of the title compounds of Formula I compound from the corresponding ortho-dihydroxy aromatic compound of Formula II, there is typically no mention of purity of the obtained product in the prior art. Therefore, the prior art does not disclose efficient method for isolation of the product with high purity and in high yield.

The above drawbacks in the prior art necessitates the development of an improved process for the preparation of alkylenedioxybenzene compounds of Formula I, which minimizes the use of aprotic solvent and the number of unit operations, provides high yield and high purity of product and is suitable for large-scale industrial scale manufacture. The inventors of the present invention have disclosed an improved, efficient and economical process for preparation of alkylenedioxybenzenes to overcome the problems mentioned herein above, for the preparation of alkylenedioxybenzene compounds of Formula I in high purity (greater than 99% by Gas Chromatography analysis) and high yield (greater than 95% weight/weight on the corresponding ortho-dihydroxy aromatic compound of Formula II), with reduced usage of aprotic solvent, and improved the process for separation and isolation of the target compound of Formula I, as well as recovery of solvents, thereby making the process industrially safe, efficient and economical.

OBJECT AND SUMMARY OF THE PRESENT INVENTION:

The present invention relates to an improved industrially safe, economical and viable process for preparing aromatic alkylenedioxybenzene compounds of Formula I from corresponding ortho- dihydroxy aromatic compounds of Formula II;

A salient feature of the present invention is the use of reduced quantity of suitable aprotic solvent such as DMSO along with stoichiometric excess of alkylene dihalide reactant of Formula III, wherein the stoichiometric excess of alkylene dihalide reactant of Formula III is between about 0.5 to about 3.0, and preferably greater than 0.8.

The inventors of the present invention have observed that use of said composite solvent system enables the completion of the desired reactions at lower temperatures resulting in improved safety and energy efficiency of the process, and enables the manufacture of the title compounds of Formula I in high purity (greater than 99% by Gas Chromatographic analysis) and high yield (greater than 95% wt./wt).

A second feature of the present invention is the simultaneous and/or sequential and/or lot wise addition of ortho-dihydroxy aromatic compound of Formula II and suitable alkali, also referred as base, to the composite solvent maintained at the desired reaction temperature, and to carry out the addition such that the ortho-dihydroxy aromatic compound of Formula II is substantially reacted at a rate faster than the rate of addition, so as to maintain a high molar ratio of aprotic solvent to the ortho-dihydroxy aromatic compound of Formula II in the reaction medium. The inventors of the present invention have observed that the best results are obtained when the composite solvent system is maintained at a preferred reaction temperature of about 60 ° C to about 100 ° C, and more preferably between about 70 °C to about 90 °C, and when the addition of ortho-dihydroxy aromatic compound of Formula II and suitable alkali, also referred as base, is carried out lot-wise over an extended period, preferably exceeding about 2 hours,

A third feature of the present invention is an improved process for separation of target compound of Formula I and recovery of unreacted alkylene dihalide at reduced temperature facilitated by the addition of water to the reaction mass and carrying out azeotropic distillation to separate out the alkylenedioxybenzene compounds of Formula I along with the unreacted alkylene dihalide, the said process being preferably carried out in a Dean-Stark type apparatus. The alkylenedioxybenzene compounds of Formula I is easily isolated from the alkylene dihalide using a conventional process such as distillation.

A fourth feature of the present invention is the removal of water from the DMSO after the separation of target compound and unreacted alkylene dihalide, to reduce the solubility of salt and alkali, also referred as base, in DMSO. The salt and excess alkali is removed by conventional techniques such as filtration prior to DMSO recovery which reduces DMSO decomposition and polymerization and improves DMSO recovery.

The inventors of the present invention have disclosed an improved novel method for the preparation of said compound of Formula I comprising use of a composite solvent, made up by mixing alkylene dihalide of Formula III and an aprotic solvent such as dimethyl sulfoxide as reaction medium, maintaining said composite solvent at preferred reaction temperature of about 60 ° C to about 100 ° C, and more preferably between about 70°C to about 90°C, and into which is added simultaneously and/or sequentially and/or lot wise the ortho-dihydroxy aromatic compound of Formula II and suitable alkali also referred as base over an extended period, preferably exceeding about 2 hours. After the completion of the reaction, the compound of Formula I so formed along with unreacted alkylene dihalide of Formula III is separated from the aprotic solvent by azeotropic distillation, the said process being preferably carried out in a Dean- Stark type apparatus, and title compound of Formula I is further purified by distillation to give high purity product having purity of more than about 99% in yield more than about 95% wt./wt. The present invention also overcomes the problem of recovery of aprotic solvent like DMSO by removing the water present in the solvent and separating the salt and excess alkali, also referred as base, by a method such as filtration prior to recovery of the DMSO solvent avoiding decomposition and polymerization, thereby increasing the recovery of aprotic solvent and making the process economical.

DETAILED DESCRIPTION OF THE INVENTION:

Reference will now be made in detail to the preferred embodiments of the invention. It is to be understood that this invention is not limited to particular embodiments described, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

Certain ranges are presented herein with numerical values being preceded by the term "about." The term "about" is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number may be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number.

Methods recited herein may be carried out in any order of the recited events which is logically possible, as well as the recited order of events. 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. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, the preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention described.

It must be noted that as used herein and in the appended claims, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as "solely", "only" and the like in connection with the recitation of claim elements, or use of a "negative" limitation.

The term contacted and/or contacting used herein refers to reacting, added, refluxing, stirring and the likes.

The term alkali cited herein is also referred as base and both herein relates to same entity.

The present invention relates to an efficient, industrially safe and economically viable process for the preparation of alkylenedioxybenzene compounds of Formula I, from the corresponding ortho-dihydroxy aromatic compound of Formula II,

Formula I Formula II wherein R 2 represents H, linear or branched Ci - C 10 alkyl or alkenyl group, cycloalkyl group, halogen selected from CI, Br, I, nitro (-N0 2 ) , alkoxy (-OR) or SR thioether (-SR) where in wherein R is selected from H or linear or branched alkyl group comprising C1-C6 carbon atoms; comprising contacting said compound of Formula II with alkylene dihalide of Formula III in the presence of a base,

Formula III wherein n = 0, 1,2, and 3, and Ri represents H, linear or branched Ci - Cio alkyl or alkenyl group, cycloalkyl group, halogen selected from CI, Br, I, nitro (-N0 2 ) , alkoxy (-OR) or SR thioether (-SR); and X is halogen CI, Br, I.

In one embodiment disclosed herein is a process for the preparation of compound of Formula I; wherein n is 0, 1, 2 or 3; Ri and R 2 independently represent H, linear or branched Ci - Cio alkyl or alkenyl group, cycloalkyl group, halogen selected from CI, Br, I, nitro (-N0 2 ), alkoxy (-OR) or SR thioether (-SR), wherein R is selected from linear or branched alkyl group comprising Cl- C6 carbon atoms; and comprising; i) preparing a mixture of alkylene dihalide of Formula III and aprotic solvent, wherein the stoichiometric excess of alkylene dihalide reactant of Formula III is between about 0.5 to about 3.0, and preferably greater than 0.8.

ii) maintaining said mixture at the preferred reaction temperature between about 60°C to about 100 °C; and

iii) simultaneously and/or sequentially, lot wise and/or continuously adding ortho- dihydroxy aromatic compound of Formula II and suitable alkali, also referred as base, to the said mixture of step ii) over a an extended period, preferably exceeding about 2 hours; and

iv) maintaining the reaction medium at the preferred reaction temperature between about 60°C to about 100°C after the addition of ortho-dihydroxy aromatic compound of Formula II and alkali, also referred as base, until the ortho-dihydroxy compound is substantially reacted;

v) separating the target compound of Formula I so formed along with the unreacted alkylene dihalide at low temperature by azeotropic distillation; and

vi) separating the unreacted alkylene dihalide of Formula III and further purifying the target compound of Formula I by distillation to get the required product in high yield more than 95% wt./wt. and purity more than about 99% by Gas Chromatographic analysis.

Herein alkali, also referred as base, is selected from the group comprising alkali metal hydroxide or alkali metal carbonate or alkali metal bicarbonate or mixtures thereof and the like that can prepare dialkalimetal salt of ortho-dihydroxy aromatic compound of Formula II. The preferred alkali, also referred as base, is sodium hydroxide.

Herein aprotic solvent is a compound that does not contain acidic hydrogen centers and which is able to form hydrogen bonds with an anion. The aprotic solvent is selected from the group comprising N,N-dimethylformamide, Ν,Ν-dimethylacetamide, acetonitrile, propionitrile and the like, nitrobenzene, benzonitrile, nitrotoluene, dimethylsulfone, tetrahydrofuran, sulfolane, dimethylsulfoxide (DMSO) or mixtures thereof. The preferred aprotic solvent is DMSO.

The first aspect of the present invention is to provide an industrially safe and economically viable process for the preparation of alkylenedioxybenzene compound of Formula I in high yield (greater than 95% wt/wt) and high purity (greater than 99% by Gas Chromatographic analysis).

The second aspect of the present invention is the reduction in quantity of aprotic solvent required.

The third aspect of the present invention is carrying out the reaction in acomposite solvent maintained at preferred reaction temperature between about 60 ° C to about 100 ° C, and more preferably between about 70 °C to about 90 °C. A fourth aspect of the present invention is the simultaneous and/or sequential, lot wise and/or continuous addition of ortho-dihydroxy aromatic compound of Formula II and suitable alkali, also referred as base, to the reaction medium over an extended period,preferably exceeding 2 hours.

The fifth aspect of the present invention is the separation of the title compound of Formula I formed along with unreacted alkylene dihalide of Formula III from the aprotic solvent by azeotropic distillation, said title compound of Formula I being further purified by distillation to give high purity product having purity of more than about 99% in yield more than about 95% wt/wt.

The sixth aspect of the present invention is the substantial removal of water, salt and/or excess alkali from the aprotic solvent prior to recovery of the aprotic solvent.

The following non limiting examples are provided to illustrate further the present invention. It will be apparent to those skilled in the art many modifications, alterations, variations to the present disclosure, both to materials, method and reaction conditions, may be practiced. All such modifications, alterations and variations are intended to be within the spirit and scope of the present inventions. It should be understood that the present invention is not construed as being limited thereto.

WORKING EXAMPLES:

The present invention is further described according to the following working examples.

Example 1: Preparation of methylenedioxybenzene (compound of Formula IA)

Dimethylsulfoxide (DMSO, 360 g) and dichloromethane (200g) were charged into a 2 liter reaction flask. The mixture was heated to 80°C under stirring. 110 g of Catechol (in 5g lots) and 88g of sodium hydroxide (in 4g lots) were simultaneously added in 22 lots each at intervals of 10 minutes maintaining the temperature of the reaction medium between 80°C and 85°C under stirring. After addition of catechol and alkali was complete, the reaction medium was stirred for lhrs till the unreacted catechol was less than 0.1% by HPLC analysis. 200 ml water was charged into the reactor and methylenedioxbenzene and unreacted dichloromethane were separated by azeotropic distillation using a Dean-Stark apparatus. The mixture of methylenedioxybenzene and dichloromethane was distilled to give HOg (100% w/w on catechol) with purity >99.0% by GC analysis and recover 120 g of unreacted dichloromethane. The moisture present in DMSO was removed and the DMSO was cooled to less than 30°C and filtered to remove salt and unreacted alkali and 315 g of DMSO (purity > 99% by GC analysis) was recovered by distillation.

Example 2: Preparation of ethylenedioxybenzene (Dimethyl enedioxybenzene) (compound of Formula IB)

Dimethylsulfoxide (DMSO, 360g) and 1,2-dichloroethane (280g) were charged into a 2 liter reaction flask. The mixture was heated to 80°C under stirring. 110 g of Catechol (in 5 g lots) and 148 g of sodium hydroxide (in 6.7 g lots) were simultaneously added in 22 lots each at intervals of 7 minutes maintaining the temperature of the reaction medium between 80°C and 85°C under stirring. After addition of catechol and alkali was complete, the reaction medium was stirred for 3 hrs till the catechol content was less than 0.1% by HPLC analysis. 200 ml water was charged into the reactor and ethyl enedioxbenzene and unreacted 1,2-dichloroethane were separated by azeotropic distillationusing a Dean-Stark apparatus.. The mixture of methylenedioxybenzene and 1,2-dichloroethane was distilled to give 115g (104.5% w/w on catechol) with purity >99.0% by GC analysis and recover 115 g of unreacted 1,2-dicloroethane. The moisture present in DMSO was removed and the DMSO was cooled to less than 30°C and filtered to remove salt and unreacted alkali. DMSO (315 g) was recovered from the mother liquor by distillation.

Example 3: Preparation of propylenedioxybenzene (trimethylenedioxybenzene) (compound of Formula IC)

Dimethylsulfoxide (DMSO, 360g) and 1, 3-dichloropropane (260g) were charged into a 2 liter reaction flask. The mixture was heated to 80°C under stirring. 110 g of Catechol (in 5 g lots) and 88 g of sodium hydroxide (in 4.0 g lots) were simultaneously added in 22 lots each at intervals of 7 minutes maintaining the temperature of the reaction medium between 80°C and 85°C under stirring. After addition of catechol and alkali was complete, the reaction medium was stirred for 2 hrs till the catechol content was less than 0.1% by HPLC analysis. 200 ml water was charged into the reactor and propyl enedioxbenzene and unreacted 1,2-dichloropropanewere separated by azeotropic distillation.. The mixture of methylenedioxybenzene and 1, 3-dichloropropane was distilled to give 112g (101.8% w/w on catechol) with purity >99.0% by GC analysis and recover DMSO was cooled to less than 30°C and filtered to remove salt and unreacted alkali. DMSO (310 g) was recovered from the mother liquor by distillation.

Example 4: Preparation of 6-Methyl-l, 3 -methyl enedioxybenzene (compound of Formula ID) Dimethylsulfoxide (DMSO, 360g) and dichloromethane (200g) were charged into a 2 liter reaction flask. The mixture was heated to 80°C under stirring. 124 g of 4-methylcatechol (in 5.6 g lots) and 88g of sodium hydroxide (in 4g lots) were simultaneously added in 22 lots each at intervals of 10 minutes maintaining the temperature of the reaction medium between 80°C and 85°C under stirring. After addition of 4-methylcatechol and alkali was complete, the reaction medium was stirred for lhrs till the unreacted 4-methylcatechol was less than 0.1% by HPLC analysis. 200 ml water was charged into the reactor and 6-Methyl-l, 3-methylenedioxybenzene and unreacted dichloromethane were separated by azeotropic distillation. The mixture of 6- Methyl- 1,3 -methyl enedioxybenzene and dichloromethane was distilled to give 118g (95.2% w/w on 4-methylcatechol) with purity >99.0% by GC analysis and recover 120 g of unreacted dichloromethane.. The moisture present in DMSO was removed and the DMSO was cooled to less than 30°C and filtered to remove salt and unreacted alkali and 310 g of DMSO (purity > 99% by GC analysis) was recovered by distillation.