WO2018150230A1 - A process for preparation of alkenyl and alkyl derivatives of alkylenedioxybenzene - Google Patents

A process for preparation of alkenyl and alkyl derivatives of alkylenedioxybenzene Download PDF

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WO2018150230A1
WO2018150230A1 PCT/IB2017/052230 IB2017052230W WO2018150230A1 WO 2018150230 A1 WO2018150230 A1 WO 2018150230A1 IB 2017052230 W IB2017052230 W IB 2017052230W WO 2018150230 A1 WO2018150230 A1 WO 2018150230A1
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formula
compound
linear
acyl halide
alkylenedioxybenzene
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PCT/IB2017/052230
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French (fr)
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Manoj Kumar Mohapatra
Ramamohanrao Bendapudi
Paul Vincent Menacherry
Vincent Paul
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Anthea Aromatics Private Limited
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
    • C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
    • C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D321/00—Heterocyclic compounds containing rings having two oxygen atoms as the only ring hetero atoms, not provided for by groups C07D317/00 - C07D319/00
    • C07D321/02—Seven-membered rings
    • C07D321/10—Seven-membered rings condensed with carbocyclic rings or ring systems

Definitions

  • the present disclosure generally relates to the method of preparation of compounds of Formula IV.
  • alkylenedioxybenzene derivatives have gained much importance in the pharmaceutical, pesticide, perfumery and food sectors due to their application as an end product or intermediates for the synthesis of wide range of finished products.
  • a large number of processes are available in the prior art for the preparation of alkylenedioxybenzene derivatives, particularly dihydrosafrole.
  • Dauksas et al. disclose a process involving 1,3-benzodioxole and acyl chloride as raw materials and using A1C13 or SnC14 as catalyst to prepare piperonyl ethyl ketone with a yield of -58%.
  • CN1907980 discloses a method comprising Friedel-Crafts acylation of 1,3- benzodioxole using propionic anhydride as the acylating agent in the presence of perchloric acid as the catalyst with a yield of -72% with no data on purity.
  • CN100473650C discloses a 3 step process to prepare dihydrosafrole comprising Friedel-Crafts acylation of catechol, catalytic hydrogenation followed by cyclization to obtain target product.
  • the disclosed process requires Zinc chloride in high stoichiometric quantity (about 1.2 moles per mole of catechol) to complete the acylation.
  • the document discloses that the reported yield of the product obtained is -74% with a purity of 98.2%.
  • CN102070596 discloses a process for the preparation of dihydrosafrole by Friedel- Crafts acylation of 1,3-benzodioxole using propionyl chloride as acylating agent in the presence of Lewis acid catalyst like Zinc chloride to prepare the acyl compound, followed by its reduction by Wolf-Kishner reaction using hydrazine hydrate with a yield of -82% with a purity of 99%.
  • the disclosed process requires Zinc chloride in high stoichiometric quantity (about 1.2 moles per mole of catechol) to complete the acylation.
  • the disclosed reaction requires the use of highly toxic and carcinogenic hydrazine hydrate.
  • EP1048664A2 discloses a process for the preparation of dihydrosafrole that comprises a 5 step reaction comprising the use of 4-hydroxyphenyl acetone as a starting material and the said starting material is subjected to catalytic hydrogenation followed by esterifi cation, rearrangement, hydrolysis and cyclization to give the target product.
  • the disclosed process fails to disclose yield or purity of the title compound so obtained.
  • WO2000040575 discloses a process for the preparation of dihydrosafrole from methylenedioxybenzene and propionic anhydride using perchloric acid as catalyst followed by using 5% Pd/C during the hydrogenation stage to obtain dihydrosafrole with a yield of 79.5% on methylenedioxybenzenewith no disclosure of purity of the product.
  • US2015038465A1 discloses a process for preparation of higher alkyl derivatives (C4 - CIO) of 1,3-benzodioxole, said process comprising use of the corresponding acyl chloride and Zinc chloride as catalyst to obtain the final product with a reported yield of 39.3%.
  • W09639133 discloses that the acylated product of 1,3-benzodioxole is difficult to purify and involved repeated treatments for decolorization.
  • Another object of the present disclosure is to provide a process for the acylation of alkylenedioxybenzene without substantial degradation of alkylenedioxybenzene or acylated product formed therefrom.
  • Yet another object of the present disclosure is to provide a process for the acylation of alkylenedioxybenzene that substantially reduces the amount of Lewis acid, such as Zinc chloride, used as catalyst.
  • Yet another object of the present disclosure is to provide a process for the acylation of alkylenedioxybenzene compounds to prepare the acylated product in high yield.
  • Yet another object of the present disclosure is to provide a process for the acylation of alkylenedioxybenzene compounds to prepare the acylated product with high purity.
  • Yet another object of the present disclosure is to provide an efficient process for preparation of alkyl and alkylene derivatives of alkylenedioxybenzene compounds without substantial degradation of any of the starting compound(s) and the desired product during the course of reaction.
  • the present disclosure generally relates to the method of preparation of compounds of Formula IV.
  • An aspect of the present disclosure relates to a process for preparation of compound of Formula IV, said process comprising the step of reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent,
  • the amphoteric oxide is selected from a group consisting of Zinc oxide, Tin oxide, Aluminum oxide, Beryllium oxide, and mixtures thereof, and the amphoteric oxide is used in a quantity ranging from 0.2 to 0.9 moles per mole of acid halide.
  • the amphoteric oxide selected is Zinc oxide, and wherein Zinc oxide is used in a quantity ranging from about 0.4 moles to about 0.6 moles per mole of acyl halide.
  • the Lewis acid is selected from a group consisting of Zinc chloride, Tin chloride, Aluminum Chloride, Beryllium chloride, and mixtures thereof, and the Lewis acid is used in a quantity ranging from 0.0 moles to about 0.5 moles per mole of acyl halide.
  • the Lewis acid selected is Zinc chloride, and wherein Zinc chloride is used in a quantity ranging from about 0.01 moles to about 0.25 moles per mole of acyl halide, and more preferably from about 0.01 moles to about 0.1 moles per mole of acyl halide.
  • the solvent is selected from the group consisting of dichloromethane, ethylene di chloride, 1 ,2-dichloropropane, or mixtures thereof.
  • the solvent selected is dichloromethane.
  • Another aspect of the present disclosure relates to a process for preparation of a compound of Formula IA, said process comprising the steps of: (a) obtaining a compound of Formula IV by reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent,
  • Still further aspect of the present disclosure relates to a process for preparation of a compound of Formula IB, said process comprising the steps of: (a) obtaining a compound of Formula IV by reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent,
  • the Nickel catalyst is Raney Nickel.
  • the acid catalyst is selected from a group consisting of p-toluene sulfonic acid, anhydrous Sodium bisulphate, anhydrous Potassium bisulphate, Nickel chloride, Ferrous sulphate, Zinc chloride or mixtures thereof.
  • the compound of Formula IB is dihydrosafrole of Formula VII.
  • the present disclosure generally relates to the method of preparation of compounds of Formula IV.
  • An aspect of the present disclosure relates to a process for preparation of compound of Formula IV, said process comprising the step of reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent,
  • the amphoteric oxide is selected from a group consisting of Zinc oxide, Tin oxide, Aluminum oxide, Beryllium oxide, and mixtures thereof, and the amphoteric oxide is used in a quantity ranging from about 0.2 moles to about 0.9 moles per mole of the acyl halide.
  • the amphoteric oxide selected is Zinc oxide, and more preferably wherein the Zinc oxide is used in a quantity ranging from about 0.4 moles to about 0.6 moles per mole of the acyl halide.
  • the Lewis acid is selected from a group consisting of Zinc chloride, Tin chloride, Aluminum Chloride, Beryllium chloride, and mixtures thereof, and the Lewis acid is used in a quantity ranging from 0.0 moles to about 0.5 moles per mole of acyl halide.
  • any other Lewis acid can be used to serve its intended purpose as laid down in the present disclosure without departing from the scope and spirit of the invention.
  • the Lewis acid selected is Zinc chloride, and more preferably wherein the Zinc chloride is used in a quantity ranging from about 0.01 moles to about 0.25 moles per mole of acyl halide and most preferably wherein Zinc chloride is used in a quantity ranging from about 0.01 moles to about 0.1 moles per mole of acyl halide.
  • the solvent is selected from the group consisting of dichloromethane, ethylene dichloride, 1 ,2-dichloropropane, other chlorinated hydrocarbons or mixtures thereof.
  • the solvent selected is dichloromethane.
  • Another aspect of the present disclosure relates to a process for preparation of a compound of Formula IA, said process comprising the steps of: (a) obtaining a compound of Formula IV by reacting an alkyl enedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent,
  • selective reduction is carried out in presence of a metal catalyst.
  • the metal catalyst is selected from precious metal catalysts such as Palladium, Platinum, Ruthenium and the likes.
  • the metal catalyst is Raney Nickel.
  • any other catalyst as known to or appreciated by a person skilled in the art can be utilized to effect selective reduction without departing from the scope and spirit of the invention.
  • said metal catalyst is supported on conventional supports such as carbon, alumina, silica and the likes.
  • dehydration is carried out in presence of a catalyst selected from p-toluene sulfonic acid, Sodium bisulphate, Potassium bisulphate, sulphuric acid and the likes.
  • a catalyst selected from p-toluene sulfonic acid, Sodium bisulphate, Potassium bisulphate, sulphuric acid and the likes.
  • any other catalyst as known to or appreciated by a person skilled in the art can be utilized to effect dehydration without departing from the scope and spirit of the invention.
  • the compound of Formula IA is isosafrole of Formula V.
  • the compound of Formula IIA is reacted with the acyl chloride of Formula IIIA in the presence of an amphoteric oxide such as Zinc oxide in combination with catalytic quantity of Lewis acid such as Zinc chloride in a suitable solvent to obtain compound of Formula IVA.
  • an amphoteric oxide such as Zinc oxide
  • Lewis acid such as Zinc chloride
  • said compound of Formula IVA is subjected to selective reduction and dehydration to obtain the compound of Formula V in high yield (greater than 100% wt./wt. of the alkylenedioxybenzene consumed) and high purity (more than 99% by GC), as shown in Scheme 1 below.
  • Formula IB said process comprising the steps of: (a) obtaining a compound of Formula ⁇ by reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent,
  • the Nickel catalyst is Raney Nickel.
  • the acid catalyst is selected from a group comprising p-toluene sulfonic acid, anhydrous Sodium bisulphate, anhydrous Potassium bisulphate, Nickel chloride, Ferrous sulphate, Zinc chloride or mixtures thereof.
  • any other acid catalyst as known to or appreciated by a person skilled in the art can be utilized to serve its intended purpose without departing from the scope and spirit of the present invention.
  • the compound of Formula IB is dihydrosafrole of Formula VII.
  • the compound of Formula IIA is reacted with the acyl chloride of Formula IIIA in the presence of an amphoteric oxide such as Zinc oxide in combination with catalytic quantity of Lewis acid such as Zinc chloride in a suitable solvent to obtain compound of Formula IVA.
  • an amphoteric oxide such as Zinc oxide
  • Lewis acid such as Zinc chloride
  • the compound of Formula IVA is directly converted to the target compound of Formula VII by reacting the compound of Formula IVA with hydrogen in presence of a composite catalyst system, wherein the composite catalyst system comprises of a Nickel catalyst, such as Raney Nickel, in combination with an acid catalyst such as p-toluene sulfonic acid, anhydrous Sodium bisulphate, anhydrous Potassium bisulphate, Nickel chloride, Ferrous sulphate, Zinc chloride and the like, and in a suitable solvent such as methanol, ethanol, n- propanol, isopropyl alcohol, sec-butanol, t-butyl alcohol and the like.
  • the reaction is carried out in a single step.
  • the reaction mass was subjected to aqueous workup to remove Zinc chloride and propionic acid, and the organic layer was separated and distilled to recover 250 g of unreacted 1,3-benzodioxole, and 310 g of methylenedioxybenzene propiophenone with GC purity > 99%.
  • the methylenedioxybenzene propiophenone was charged into a 2 litre autoclave along with 500 g of isopropyl alcohol, 15g of Raney Nickel catalyst and 0.5 g of anhydrous sodium hydrogen sulphate. The mixture was maintained at 110°C under hydrogen at 100 psi pressure till unreacted methylenedioxybenzene propiophenone reduced to less than 0.5% as observed by GC analysis.
  • the reaction mass was subjected to aqueous workup to remove Zinc chloride and propionic acid, and the organic layer was separated and distilled to recover 64 g of unreacted 1,3-benzodioxole and 71 g of methyl enedioxybenzene propiophenone with a GC purity of > 99%.
  • the methylenedioxybenzene propiophenone was charged into a 1 liter autoclave along with 125 g of isopropyl alcohol, 4 g of Raney Nickel catalyst and 0.1 g of anhydrous sodium hydrogen sulphate.
  • the mixture was maintained at 110°C under hydrogen at 100 psi pressure till unreacted methylenedioxybenzene propiophenone was reduced to less than 0.5% by GC analysis.
  • the catalyst was separated, and the crude was distilled to give 61 g of dihydrosafrole with a yield of 105.2% (wt./wt. on 1,3-benzodioxole consumed) and purity of > 99% by GC analysis.
  • reaction mass was subjected to aqueous workup to remove Zinc chloride and propionic acid and the organic layer was separated and distilled to recover 39 g of unreacted 1,3-benzodioxole and 56 g of methylenedioxybenzene propiophenone with a yield of 58.7% (wt./wt. on 1,3-benzodioxole consumed).
  • this reaction approximately 30 g of high boiling distillation residue was obtained.
  • Example 6 The reaction mass was subjected to aqueous workup to remove Zinc chloride and propionic acid and the organic layer was separated and distilled to recover 245 g of unreacted 1,3-benzodioxole, and 311 g of methylenedioxybenzene propiophenone with a GC purity of >99%.
  • the methylenedioxybenzene propiophenone was subjected to selective reduction and dehydration as discussed in Example 1 to obtain 271 g of dihydrosafrole with a yield of 111.5% (wt./wt. on 1,3-benzodioxole consumed) and purity of > 99% by GC analysis.
  • Example 6 Example 6
  • the reaction mass was subjected to aqueous workup to remove Zinc chloride and propionic acid and the organic layer was separated and distilled to recover 60 g of unreacted 1,3-benzodioxole, and 80 g of methylenedioxybenzene propiophenone with a GC purity of > 99%.
  • the methylenedioxybenzene propiophenone along with 125 g of isopropyl alcohol, 0. lg of sodium bicarbonate and 4.0 g of Raney Nickel catalyst were charged in a 1 liter autoclave.
  • the mixture was hydrogenated under 100 p.s.i. hydrogen pressure at 110°C till the unreacted MDP was reduced to less than 0.5% by GC analysis.
  • the catalyst was separated by filtration and the crude was distilled to obtain 75 g of a-ethyl-l,3-benzodioxole-5-methanol with purity of >99% by GC analysis.
  • the a-ethyl-l,3-benzodioxole-5-methanol along with 200 g of toluene and 0.5g of 4-methyl benzenesulfonic acid (PTSA) was refluxed at 95°C in a Dean-Stark apparatus for 2 hrs.
  • the organic layer was subjected to aqueous workup to remove PTSA, and distilled to obtain 65 g of isosafrole with a yield of 105% (wt./wt. on 1,3-benzodioxole consumed) and purity of > 99% by GC analysis.
  • the reaction mass was subjected to aqueous workup to remove Zinc chloride and butanoic acid and the organic layer was separated and distilled to recover 65 g of unreacted 1,3-benzodioxole and 75 g of l-(l,3-benzodioxol-5-yl)-l-butanone with a GC purity of > 99%.
  • the l-(l,3-benzodioxol-5-yl)-l-butanone was subjected to selective reduction and dehydration as discussed in Example 2 to obtain 66 g of 5-butyl-l,3-benzodioxole with a yield of 115.8% (wt./wt. on 1,3-benzodioxole consumed) and purity of > 99% by GC analysis.
  • reaction mass was subjected to aqueous workup to remove Zinc chloride and propionic acid and the organic layer was separated and distilled to recover 85 g of unreacted 1 ,4-benzodioxane and 62 g of ethyl enedioxybenzene propiophenone with a GC purity of > 99%.
  • the ethyl enedioxybenzene propiophenone was subjected to selective reduction and dehydration as discussed in example 2 to obtain 53 g of 6-propyl-l,4-benzodioxane with a yield of 104% (wt./wt. on 1 ,4-benzodioxane consumed) and purity of > 99% by GC analysis.
  • the present disclosure provides process(es) to overcome the problems associated with conventional process(es) for the acylation of alkylenedioxybenzene compound(s). [0083] The present disclosure provides a process for the acylation of alkylenedioxybenzene compounds without substantial degradation of the alkylenedioxybenzene or acylated products formed therefrom.
  • the present disclosure provides a process for the acylation of alkylenedioxybenzene compounds that substantially reduces the amount of Lewis acid, such as Zinc chloride, required as catalyst.
  • the present disclosure provides a process for the acylation of alkylenedioxybenzene compounds to obtain the acyl compound of Formula IV in high yield (greater than 100% wt./wt. on the alkylenedioxybenzene consumed).
  • the present disclosure provides a process for the acylation of alkylenedioxybenzene compounds to obtain the acylated product of Formula IV with high purity (greater than 99% by GC analysis).
  • the present disclosure provides an efficient process for preparation of alkyl and alkylene derivatives of alkylenedioxybenzene compounds without substantial degradation of any of the starting compound(s) and the desired product during the course of reaction.

Abstract

The present disclosure generally relates to the method of preparation of compounds of Formula IV. An aspect of the present disclosure relates to a process for preparation of compound of Formula IV, said process comprising the step of reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent, characterized in that the step of reacting the alkylenedioxybenzene compound of Formula II with the acyl halide of Formula III is effected in the presence of an amphoteric oxide so as to in-situ quench the compound of formula H-X formed during the course of the reaction, thereby substantially eliminating degradation of the compounds of Formula IV and Formula II.

Description

A PROCESS FOR PREPARATION OF ALKENYL AND ALKYL DERIVATIVES OF
ALKYLENEDIOXYBENZENE
FIELD OF THE INVENTION
[0001] The present disclosure generally relates to the method of preparation of compounds of Formula IV. In particular, the present disclosure relates to a process for preparation of the compound of Formula IV by reacting an alkyl enedioxybenzene compound of Formula II with an acyl halide of Formula III without substantial degradation of the compounds of Formula IV and Formula II during the course of reaction, wherein Rl, R2 and R3 independently represent H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R) group, wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; n= 1, 2, 3, 4, 5, 6, 7 or 8; and X= F, CI, Br or I.
Figure imgf000002_0001
Formula Γν~ Formula II Formula III
[0002] The present disclosure also provides for process(es) for preparation of compound of Formula IA and process(es) for preparation of compound of Formula IB, wherein Rl, R2 and R3 independently represent H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R) group, wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; and n= 1, 2, 3, 4, 5, 6, 7 or 8.
Figure imgf000002_0002
BACKGROUND OF THE INVENTION
[0003] The following background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
[0004] In last few years, alkylenedioxybenzene derivatives have gained much importance in the pharmaceutical, pesticide, perfumery and food sectors due to their application as an end product or intermediates for the synthesis of wide range of finished products. A large number of processes are available in the prior art for the preparation of alkylenedioxybenzene derivatives, particularly dihydrosafrole.
[0005] Dauksas et al. (Pharmaceutical Chemistry Journal, 1987, 21, 569-573) disclose a process involving 1,3-benzodioxole and acyl chloride as raw materials and using A1C13 or SnC14 as catalyst to prepare piperonyl ethyl ketone with a yield of -58%.
[0006] Zhu et al. (Chemical Research and Application, 2003, 15, 417-418) discloses acylation of 1,3-benzodioxole using propionyl chloride in the presence of catalytic A1C13 to obtain piperonyl ethyl ketone with a reported yield of 78%.
[0007] CN1907980 discloses a method comprising Friedel-Crafts acylation of 1,3- benzodioxole using propionic anhydride as the acylating agent in the presence of perchloric acid as the catalyst with a yield of -72% with no data on purity.
[0008] CN100473650C discloses a 3 step process to prepare dihydrosafrole comprising Friedel-Crafts acylation of catechol, catalytic hydrogenation followed by cyclization to obtain target product. However, the disclosed process requires Zinc chloride in high stoichiometric quantity (about 1.2 moles per mole of catechol) to complete the acylation. Further, the document discloses that the reported yield of the product obtained is -74% with a purity of 98.2%.
[0009] CN102070596 discloses a process for the preparation of dihydrosafrole by Friedel- Crafts acylation of 1,3-benzodioxole using propionyl chloride as acylating agent in the presence of Lewis acid catalyst like Zinc chloride to prepare the acyl compound, followed by its reduction by Wolf-Kishner reaction using hydrazine hydrate with a yield of -82% with a purity of 99%. However, the disclosed process requires Zinc chloride in high stoichiometric quantity (about 1.2 moles per mole of catechol) to complete the acylation. Further, the disclosed reaction requires the use of highly toxic and carcinogenic hydrazine hydrate. [0010] EP1048664A2 discloses a process for the preparation of dihydrosafrole that comprises a 5 step reaction comprising the use of 4-hydroxyphenyl acetone as a starting material and the said starting material is subjected to catalytic hydrogenation followed by esterifi cation, rearrangement, hydrolysis and cyclization to give the target product. The disclosed process fails to disclose yield or purity of the title compound so obtained.
[0011] WO2000040575 discloses a process for the preparation of dihydrosafrole from methylenedioxybenzene and propionic anhydride using perchloric acid as catalyst followed by using 5% Pd/C during the hydrogenation stage to obtain dihydrosafrole with a yield of 79.5% on methylenedioxybenzenewith no disclosure of purity of the product.
[0012] US2015038465A1 discloses a process for preparation of higher alkyl derivatives (C4 - CIO) of 1,3-benzodioxole, said process comprising use of the corresponding acyl chloride and Zinc chloride as catalyst to obtain the final product with a reported yield of 39.3%.
[0013] Sarvari et al (Journal of Organic Chemistry, 69, 2004, 6953-6956] discloses the use of Zinc oxide as a catalyst in Friedel-Crafts acylation of benzene compounds However, the disclosed process requires Zinc oxide in high stoichiometric quantity and the processes did not specifically pertain to acylation of alkylenedioxybenzene compounds.
[0014] It is seen that a large number of processes are reported in the prior art for the preparation of alkylenedioxybenzenes derivatives, particularly dihydrosafrole by acylation with an acyl halide in the presence of a Lewis acid catalyst such as Zinc chloride. However, during the acylation reaction, the corresponding hydrogen halide is formed which cleaves the -O- (CH2)m-0- ring of the starting and the final product. This results in the synthesis of product with low yield and high impurities
[0015] W09639133 discloses that the acylated product of 1,3-benzodioxole is difficult to purify and involved repeated treatments for decolorization.
[0016] From careful scrutiny of these documents amongst others, a person skilled in the art would immediately realize that the acylation of alkylenedioxybenzene compounds using conventional processes result in synthesis of the end product in low yield and low purity, as -O- (CH2)m-0- ring of the reactant and product are very susceptible to cleavage under acidic conditions. There is, therefore, a need in the art for an efficient process for preparation of alkyl and alkylene derivatives of alkylenedioxybenzene compounds without substantial degradation of any of the starting compound(s) and the desired product during the course of reaction. OBJECTS OF THE INVENTION
[0017] It is an object of the present disclosure to overcome the problems associated with conventional process(es) for the acylation of alkylenedioxybenzene compound(s).
[0018] Another object of the present disclosure is to provide a process for the acylation of alkylenedioxybenzene without substantial degradation of alkylenedioxybenzene or acylated product formed therefrom.
[0019] Yet another object of the present disclosure is to provide a process for the acylation of alkylenedioxybenzene that substantially reduces the amount of Lewis acid, such as Zinc chloride, used as catalyst.
[0020] Yet another object of the present disclosure is to provide a process for the acylation of alkylenedioxybenzene compounds to prepare the acylated product in high yield.
[0021] Yet another object of the present disclosure is to provide a process for the acylation of alkylenedioxybenzene compounds to prepare the acylated product with high purity.
[0022] Yet another object of the present disclosure is to provide an efficient process for preparation of alkyl and alkylene derivatives of alkylenedioxybenzene compounds without substantial degradation of any of the starting compound(s) and the desired product during the course of reaction.
[0023] Various objects, features, aspects and advantages of the present invention will become more apparent from the detailed description of the invention herein below along with the accompanying figures in which like numerals represent like components.
SUMMARY
[0024] The present disclosure generally relates to the method of preparation of compounds of Formula IV. In particular, the present disclosure relates to a process for preparation of the compound of Formula IV by reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III without substantial degradation of the compounds of Formula IV and Formula II during the course of reaction, wherein Rl, R2 and R3 independently represent H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R) group, wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; n= 1, 2, 3, 4, 5, 6, 7 or 8; and X= F, CI, Br or I.
Figure imgf000006_0001
Formula IV Formula II Formula III
[0025] The present disclosure also provides for process(es) for preparation of compound of Formula IA and process(es) for preparation of compound of Formula IB, wherein Rl, R2 and R3 independently represent H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R) group, wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; and n= 1, 2, 3, 4, 5, 6, 7 or 8.
Figure imgf000006_0002
Formula IA Formula IB
[0026] An aspect of the present disclosure relates to a process for preparation of compound of Formula IV, said process comprising the step of reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent,
Figure imgf000006_0003
Formula TV Formula II Formula III wherein Rl, R2 and R3 independently represent H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R) group, wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; n= 1, 2, 3, 4, 5, 6, 7 or 8; and X= F, CI, Br or I; characterized in that the step of reacting the alkylenedioxybenzene compound of Formula II with the acyl halide of Formula III is effected in presence of at least one amphoteric oxide and preferably one Lewis acid, and further characterized in that the in-situ quenching of compound of formula H-X formed during the course of the reaction is effected, so as to substantially eliminate degradation of the compounds of Formula IV and Formula II.
[0027] In an embodiment, the amphoteric oxide is selected from a group consisting of Zinc oxide, Tin oxide, Aluminum oxide, Beryllium oxide, and mixtures thereof, and the amphoteric oxide is used in a quantity ranging from 0.2 to 0.9 moles per mole of acid halide.
[0028] In an embodiment, the amphoteric oxide selected is Zinc oxide, and wherein Zinc oxide is used in a quantity ranging from about 0.4 moles to about 0.6 moles per mole of acyl halide.
[0029] In an embodiment, the Lewis acid is selected from a group consisting of Zinc chloride, Tin chloride, Aluminum Chloride, Beryllium chloride, and mixtures thereof, and the Lewis acid is used in a quantity ranging from 0.0 moles to about 0.5 moles per mole of acyl halide.
[0030] In an embodiment, the Lewis acid selected is Zinc chloride, and wherein Zinc chloride is used in a quantity ranging from about 0.01 moles to about 0.25 moles per mole of acyl halide, and more preferably from about 0.01 moles to about 0.1 moles per mole of acyl halide.
[0031] In an embodiment, the solvent is selected from the group consisting of dichloromethane, ethylene di chloride, 1 ,2-dichloropropane, or mixtures thereof.
[0032] In an embodiment, the solvent selected is dichloromethane.
[0033] Another aspect of the present disclosure relates to a process for preparation of a compound of Formula IA, said process comprising the steps of: (a) obtaining a compound of Formula IV by reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent,
Figure imgf000008_0001
Formula IV Formula II Formula III wherein Rl, R2 and R3 independently represents H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R), wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; n= 1, 2, 3, 4, 5, 6, 7 or 8; and X= F, CI, Br or I; and
(b) effecting selective reduction followed by dehydration of the compound of Formula Γν to obtain the corresponding compound of Formula IA;
Figure imgf000008_0002
Formula IA wherein Rl, R2 and R3 independently represents H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R), wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; and n= 1, 2, 3, 4, 5, 6, 7 or 8; characterized in that the reaction of said alkylenedioxybenzene compound of Formula II with said acyl halide of Formula III is effected in presence of at least one amphoteric oxide and preferably one Lewis acid, and further characterized in that the in-situ quenching of compound of formula H-X, formed during the course of the reaction, is effected so as to substantially eliminate degradation of the compound of Formula IV and Formula II.
[0034] Still further aspect of the present disclosure relates to a process for preparation of a compound of Formula IB, said process comprising the steps of: (a) obtaining a compound of Formula IV by reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent,
Figure imgf000009_0001
Formula IV Formula II Formula III wherein Rl, R2 and R3 independently represents H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R), wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; n= 1, 2, 3, 4, 5, 6, 7 or 8; and X= F, CI, Br or I; and
(b) reacting the compound of Formula IV with hydrogen gas in presence of a composite catalyst comprising a Nickel catalyst and an acid catalyst to obtain the compound of Formula IB;
Figure imgf000009_0002
Formula IB wherein Rl, R2 and R3 independently represents H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R), wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; and n= 1, 2, 3, 4, 5, 6, 7 or 8; characterized in that the reaction of said alkylenedioxybenzene compound of Formula II with said acyl halide of Formula III is effected in presence of at least one amphoteric oxide and preferably one Lewis acid, and further characterized in that the in-situ quenching of compound of formula H-X formed during the course of the reaction is effected, so as to substantially eliminate degradation of the compounds of Formula IV and Formula II.
[0035] In an embodiment, the Nickel catalyst is Raney Nickel. In an embodiment, the acid catalyst is selected from a group consisting of p-toluene sulfonic acid, anhydrous Sodium bisulphate, anhydrous Potassium bisulphate, Nickel chloride, Ferrous sulphate, Zinc chloride or mixtures thereof.
[0036] In an embodiment, the compound of Formula IB is dihydrosafrole of Formula VII.
Figure imgf000010_0001
Formula VII
[0037] Various objects, features, aspects and advantages of the inventive subject matter will become more apparent from the following detailed description of preferred embodiments, along with the accompanying drawings in which like numerals represent like components.
DETAILED DESCRIPTION OF THE INVENTION
[0038] Unless the context requires otherwise, throughout the specification which follow, the word "comprise" and variations thereof, such as, "comprises" and "comprising" are to be construed in an open, inclusive sense that is as "including, but not limited to."
[0039] In the following description, numerous specific details are set forth in order to provide a thorough understanding of embodiments of the present invention. It will be apparent to one skilled in the art that embodiments of the present invention may be practiced without some of these specific details.
[0040] Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.
[0041] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. It should also be noted that the term "or" is generally employed in its sense including "and/or" unless the content clearly dictates otherwise.
[0042] Each of the appended claims defines a separate invention, which for infringement purposes is recognized as including equivalents to the various elements or limitations specified in the claims. Depending on the context, all references below to the "invention" may in some cases refer to certain specific embodiments only. In other cases it will be recognized that references to the "invention" will refer to subject matter recited in one or more, but not necessarily all, of the claims.
[0043] Various terms as used herein are shown below. To the extent a term used in a claim is not defined below, 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.
[0044] Each of the appended claims defines a separate invention, which for infringement purposes is recognized as including equivalents to the various elements or limitations specified in the claims. Depending on the context, all references below to the "invention" may in some cases refer to certain specific embodiments only. In other cases it will be recognized that references to the "invention" will refer to subject matter recited in one or more, but not necessarily all, of the claims.
[0045] Various terms as used herein are shown below. To the extent a term used in a claim is not defined below, 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.
[0046] The embodiments are in such detail as to clearly 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 as defined by the appended claims.
[0047] The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments. Reference will now be made in detail to the exemplary embodiments of the present invention.
[0048] The present disclosure generally relates to the method of preparation of compounds of Formula IV. In particular, the present disclosure relates to a process for preparation of the compound of Formula IV by reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III without substantial degradation of the compounds of Formula IV and Formula II during the course of reaction, wherein Rl, R2 and R3 independently represent H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R) group, wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; n= 1, 2, 3, 4, 5, 6, 7 or 8; and X= F, CI, Br or I.
Figure imgf000012_0001
Formula IV Formula II Formula III
[0049] The present disclosure also provides for process(es) for preparation of compound of Formula IA and process(es) for preparation of compound of Formula IB, wherein Rl, R2 and R3 independently represent H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R) group, wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; and n= 1, 2, 3, 4, 5, 6, 7 or 8.
Figure imgf000012_0002
Formula IA Formula IB
[0050] An aspect of the present disclosure relates to a process for preparation of compound of Formula IV, said process comprising the step of reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent,
Figure imgf000012_0003
Formula TV Formula II Formula III wherein Rl, R2 and R3 independently represent H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R) group, wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; n= 1, 2, 3, 4, 5, 6, 7 or 8; and X= F, CI, Br or I; characterized in that the step of reacting the alkylenedioxybenzene compound of Formula II with the acyl halide of Formula III is effected in presence of at least one amphoteric oxide and preferably one Lewis acid, and further characterized in that the in-situ quenching of compound of formula H-X, formed during the course of the reaction, is effected so as to substantially eliminate degradation of the compounds of Formula IV and Formula II.
[0051] In an embodiment, the amphoteric oxide is selected from a group consisting of Zinc oxide, Tin oxide, Aluminum oxide, Beryllium oxide, and mixtures thereof, and the amphoteric oxide is used in a quantity ranging from about 0.2 moles to about 0.9 moles per mole of the acyl halide. However, a person skilled in the art would appreciate that any other amphoteric oxide can be used to serve its intended purpose as laid down in the present disclosure without departing from the scope and spirit of the invention. In a preferred embodiment, the amphoteric oxide selected is Zinc oxide, and more preferably wherein the Zinc oxide is used in a quantity ranging from about 0.4 moles to about 0.6 moles per mole of the acyl halide.
[0052] In an embodiment, the Lewis acid is selected from a group consisting of Zinc chloride, Tin chloride, Aluminum Chloride, Beryllium chloride, and mixtures thereof, and the Lewis acid is used in a quantity ranging from 0.0 moles to about 0.5 moles per mole of acyl halide. However, a person skilled in the art would appreciate that any other Lewis acid can be used to serve its intended purpose as laid down in the present disclosure without departing from the scope and spirit of the invention. In a preferred embodiment, the Lewis acid selected is Zinc chloride, and more preferably wherein the Zinc chloride is used in a quantity ranging from about 0.01 moles to about 0.25 moles per mole of acyl halide and most preferably wherein Zinc chloride is used in a quantity ranging from about 0.01 moles to about 0.1 moles per mole of acyl halide.
[0053] In an embodiment, the solvent is selected from the group consisting of dichloromethane, ethylene dichloride, 1 ,2-dichloropropane, other chlorinated hydrocarbons or mixtures thereof. However, a person skilled in the art would appreciate that any other solvent can be used to serve its intended purpose as laid down in the present disclosure without departing from the scope and spirit of the invention. In a preferred embodiment, the solvent selected is dichloromethane. [0054] Another aspect of the present disclosure relates to a process for preparation of a compound of Formula IA, said process comprising the steps of: (a) obtaining a compound of Formula IV by reacting an alkyl enedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent,
Figure imgf000014_0001
Formula IV Formula II Formula III wherein Rl, R2 and R3 independently represents H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R), wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; n= 1, 2, 3, 4, 5, 6, 7 or 8; and X= F, CI, Br or I; and
(b) effecting selective reduction followed by dehydration of the compound of Formula Γν to obtain the compound of Formula IA;
Figure imgf000014_0002
Formula IA wherein Rl, R2 and R3 independently represents H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R), wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; and n= 1, 2, 3, 4, 5, 6, 7 or 8; characterized in that the reaction of said alkylenedioxybenzene compound of Formula II with said acyl halide of Formula III is effected in presence of at least one amphoteric oxide and preferably one Lewis acid, and further characterized in that the in-situ quenching of compound of formula H-X formed during the course of the reaction is effected, so as to substantially eliminate degradation of the compounds of Formula IV and Formula II. [0055] In an embodiment, selective reduction is carried out in presence of a metal catalyst. In an embodiment, the metal catalyst is selected from precious metal catalysts such as Palladium, Platinum, Ruthenium and the likes. In a preferred embodiment, the metal catalyst is Raney Nickel. However, any other catalyst as known to or appreciated by a person skilled in the art can be utilized to effect selective reduction without departing from the scope and spirit of the invention. In an embodiment, said metal catalyst is supported on conventional supports such as carbon, alumina, silica and the likes.
[0056] In an embodiment, dehydration is carried out in presence of a catalyst selected from p-toluene sulfonic acid, Sodium bisulphate, Potassium bisulphate, sulphuric acid and the likes. However, any other catalyst as known to or appreciated by a person skilled in the art can be utilized to effect dehydration without departing from the scope and spirit of the invention.
[0057] In a preferred embodiment, the compound of Formula IA is isosafrole of Formula V.
Figure imgf000015_0001
Formula V
[0058] In an embodiment, the compound of Formula IIA is reacted with the acyl chloride of Formula IIIA in the presence of an amphoteric oxide such as Zinc oxide in combination with catalytic quantity of Lewis acid such as Zinc chloride in a suitable solvent to obtain compound of Formula IVA.
Figure imgf000015_0002
Formula IIA Formula IIIA Formula IVA
[0059] In an embodiment, said compound of Formula IVA is subjected to selective reduction and dehydration to obtain the compound of Formula V in high yield (greater than 100% wt./wt. of the alkylenedioxybenzene consumed) and high purity (more than 99% by GC), as shown in Scheme 1 below.
Figure imgf000016_0001
Formula IVA Formula V
Scheme - 1
[0060] Still further aspect of the present disclosure relates to a process for preparation of a compound of Formula IB, wherein Rl, R2 and R3 independently represents H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R), wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; and n= 1, 2, 3, 4, 5, 6, 7 or 8;
Figure imgf000016_0002
Formula IB said process comprising the steps of: (a) obtaining a compound of Formula Γν by reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent,
Figure imgf000016_0003
Formula IV Formula II Formula III wherein Rl, R2 and R3 independently represents H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R), wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; n= 1, 2, 3, 4, 5, 6, 7 or 8; and X= F, CI, Br or I; and
(b) reacting the compound of Formula IV with hydrogen gas in presence of a composite catalyst comprising a Nickel catalyst and an acid catalyst to obtain the compound of Formula IB; characterized in that the reaction of said alkylenedioxybenzene compound of Formula II with said acyl halide of Formula III is effected in presence of at least one amphoteric oxide and preferably one Lewis acid, and further characterized in that the in-situ quenching of compound of formula H-X formed during the course of the reaction is effected, so as to substantially eliminate degradation of the compounds of Formula IV and Formula II.
[0061] In a preferred embodiment, the Nickel catalyst is Raney Nickel. However, any other Nickel catalyst as known to or appreciated by a person skilled in the art can be utilized to serve its intended purpose without departing from the scope and spirit of the present invention. In an embodiment, the acid catalyst is selected from a group comprising p-toluene sulfonic acid, anhydrous Sodium bisulphate, anhydrous Potassium bisulphate, Nickel chloride, Ferrous sulphate, Zinc chloride or mixtures thereof. However, any other acid catalyst as known to or appreciated by a person skilled in the art can be utilized to serve its intended purpose without departing from the scope and spirit of the present invention.
[0062] In a preferred embodiment, the compound of Formula IB is dihydrosafrole of Formula VII.
Figure imgf000017_0001
Formula VII
[0063] In an embodiment, the compound of Formula IIA is reacted with the acyl chloride of Formula IIIA in the presence of an amphoteric oxide such as Zinc oxide in combination with catalytic quantity of Lewis acid such as Zinc chloride in a suitable solvent to obtain compound of Formula IVA.
Figure imgf000017_0002
Formula IIA Formula IIIA Formula IVA [0064] In an embodiment, the compound of Formula IVA is directly converted to the target compound of Formula VII by reacting the compound of Formula IVA with hydrogen in presence of a composite catalyst system, wherein the composite catalyst system comprises of a Nickel catalyst, such as Raney Nickel, in combination with an acid catalyst such as p-toluene sulfonic acid, anhydrous Sodium bisulphate, anhydrous Potassium bisulphate, Nickel chloride, Ferrous sulphate, Zinc chloride and the like, and in a suitable solvent such as methanol, ethanol, n- propanol, isopropyl alcohol, sec-butanol, t-butyl alcohol and the like. In an embodiment, the reaction is carried out in a single step.
EXAMPLES
Example 1
[0065] Preparation of dihydrosafrole (using 0.5 moles of Zinc oxide and 0.05 moles of Zinc chloride per mole of acyl chloride, and ethylene dichloride as solvent)
[0066] 488 g of 1,3-benzodioxole and 500 g of ethylene dichloride were charged into a 3 litre reaction flask and the mixture was cooled to 0°C under stirring. 162 g of Zinc oxide and 27 g of Zinc chloride were added under stirring. Subsequently, 370g of propionyl chloride was added to the above mixture in 4 hours, maintaining the temperature of the reaction medium between 0°C and 5°C under stirring. The reaction medium was stirred for another 1 hour until the acylation reaction was substantially completed. The reaction mass was subjected to aqueous workup to remove Zinc chloride and propionic acid, and the organic layer was separated and distilled to recover 250 g of unreacted 1,3-benzodioxole, and 310 g of methylenedioxybenzene propiophenone with GC purity > 99%. The methylenedioxybenzene propiophenone was charged into a 2 litre autoclave along with 500 g of isopropyl alcohol, 15g of Raney Nickel catalyst and 0.5 g of anhydrous sodium hydrogen sulphate. The mixture was maintained at 110°C under hydrogen at 100 psi pressure till unreacted methylenedioxybenzene propiophenone reduced to less than 0.5% as observed by GC analysis. The catalyst was separated and the crude was distilled to give 270 g of dihydrosafrole with a yield of 113.4% (wt./wt. on 1,3-benzodioxole consumed) and purity of >99% by GC analysis. Example 2
[0067] Preparation of dihydrosafrole (using 0.55 moles of Zinc oxide per mole of acyl chloride without addition of Zinc chloride, and ethylene dichloride as solvent)
[0068] 122 g of 1,3-benzodioxole and 150 g of ethylene dichloride were charged into a 1 litre reaction flask and the mixture was cooled to 0°C under stirring followed by the addition of 44.5 g of Zinc oxide under stirring. Subsequently, 92.5 g of propionyl chloride was added to the above mixture in 4 hours while maintaining the temperature of the reaction medium between 0°C and 5°C under constant stirring. The reaction medium was stirred for another 1 hour until the acylation reaction was substantially completed. The reaction mass was subjected to aqueous workup to remove Zinc chloride and propionic acid, and the organic layer was separated and distilled to recover 64 g of unreacted 1,3-benzodioxole and 71 g of methyl enedioxybenzene propiophenone with a GC purity of > 99%. The methylenedioxybenzene propiophenone was charged into a 1 liter autoclave along with 125 g of isopropyl alcohol, 4 g of Raney Nickel catalyst and 0.1 g of anhydrous sodium hydrogen sulphate. The mixture was maintained at 110°C under hydrogen at 100 psi pressure till unreacted methylenedioxybenzene propiophenone was reduced to less than 0.5% by GC analysis. The catalyst was separated, and the crude was distilled to give 61 g of dihydrosafrole with a yield of 105.2% (wt./wt. on 1,3-benzodioxole consumed) and purity of > 99% by GC analysis.
Example 3
[0069] Preparation of dihydrosafrole (without addition of Zinc oxide, using 0.55 moles of Zinc chloride per mole of acyl chloride, and ethylene dichloride as solvent)
[0070] 122 g of 1,3-benzodioxole and 150 g of ethylene dichloride were charged into a 1 litre reaction flask and the mixture was cooled to 0°C under stirring. 75 g of Zinc chloride was added under stirring at 0°C. Subsequently, 92.5 g of propionyl chloride added to the above mixture in 4 hours maintaining the temperature of the reaction medium between 0°C and 5°C under stirring. The reaction medium was stirred for another 1 hour. However, it was observed that only 20% of the 1,3-benzodioxole was converted, therefore, the experiment was abandoned. Example 4:
[0071] Preparation of dihydrosafrole (without using Zinc oxide, using 1.00 moles of Zinc chloride per mole of acyl chloride, and ethylene dichloride as solvent)
[0072] 122 g of 1,3-benzodioxole and 150 g of ethylene dichloride were charged into a 1 litre reaction flask and the mixture was cooled to 0°C under stirring. 136 g of Zinc chloride was added under stirring at 0°C. Subsequently, 92.5 g of propionyl chloride was added to the above mixture in 4 hours maintaining the temperature of the reaction medium between 0°C and 5°C under stirring. The reaction medium was stirred for another 1 hour till the acylation reaction was substantially completed. The reaction mass was subjected to aqueous workup to remove Zinc chloride and propionic acid and the organic layer was separated and distilled to recover 39 g of unreacted 1,3-benzodioxole and 56 g of methylenedioxybenzene propiophenone with a yield of 58.7% (wt./wt. on 1,3-benzodioxole consumed). In this reaction, approximately 30 g of high boiling distillation residue was obtained.
Example 5
[0073] Preparation of dihydrosafrole (using 0.5 moles of Zinc oxide and 0.05 moles of Zinc chloride per mole of acyl chloride using dichloromethane as solvent)
[0074] 488 g of 1,3-benzodioxole and 750 g of dichloromethane were charged into a 3 liter reaction flask and the mixture was cooled to 0°C under stirring. 162 g of Zinc oxide and 27 g of Zinc chloride were added under stirring at 0°C. Subsequently, 370 g of propionyl chloride was added to the above mixture in 4 hours, maintaining the temperature of the reaction medium between 0°C and 5°C under stirring. The reaction medium was stirred for another 1 hour till the acylation reaction was substantially completed. The reaction mass was subjected to aqueous workup to remove Zinc chloride and propionic acid and the organic layer was separated and distilled to recover 245 g of unreacted 1,3-benzodioxole, and 311 g of methylenedioxybenzene propiophenone with a GC purity of >99%. The methylenedioxybenzene propiophenone was subjected to selective reduction and dehydration as discussed in Example 1 to obtain 271 g of dihydrosafrole with a yield of 111.5% (wt./wt. on 1,3-benzodioxole consumed) and purity of > 99% by GC analysis. Example 6
[0075] Preparation of isosafrole (using 0.5 moles of Zinc oxide and 0.05 moles of Zinc chloride per mole of acyl chloride using ethylene dichloride as solvent)
[0076] 122 g of 1,3-benzodioxole and 150 g of ethylene dichloride were charged into a 1 litre reaction flask and the mixture was cooled to 0°C under stirring. 41 g of Zinc oxide and 7 g of Zinc chloride were added under stirring. Subsequently, 92.5 g of propionyl chloride was added in 3 hours maintaining the temperature of the reaction medium between 0°C and 5°C under stirring. The reaction medium was stirred for another 1 hour till the acylation reaction was substantially completed. The reaction mass was subjected to aqueous workup to remove Zinc chloride and propionic acid and the organic layer was separated and distilled to recover 60 g of unreacted 1,3-benzodioxole, and 80 g of methylenedioxybenzene propiophenone with a GC purity of > 99%. The methylenedioxybenzene propiophenone along with 125 g of isopropyl alcohol, 0. lg of sodium bicarbonate and 4.0 g of Raney Nickel catalyst were charged in a 1 liter autoclave. The mixture was hydrogenated under 100 p.s.i. hydrogen pressure at 110°C till the unreacted MDP was reduced to less than 0.5% by GC analysis. The catalyst was separated by filtration and the crude was distilled to obtain 75 g of a-ethyl-l,3-benzodioxole-5-methanol with purity of >99% by GC analysis. The a-ethyl-l,3-benzodioxole-5-methanol along with 200 g of toluene and 0.5g of 4-methyl benzenesulfonic acid (PTSA) was refluxed at 95°C in a Dean-Stark apparatus for 2 hrs. The organic layer was subjected to aqueous workup to remove PTSA, and distilled to obtain 65 g of isosafrole with a yield of 105% (wt./wt. on 1,3-benzodioxole consumed) and purity of > 99% by GC analysis.
Example 7
[0077] Preparation of 5-butyl-l,3-Benzodioxole (using 0.5 moles of Zinc oxide and 0.05 moles of Zinc chloride per mole of acyl chloride using dichloromethane as solvent)
[0078] 122 g of 1,3-benzodioxole and 190 g of dichloromethane were charged into a 1 litre reaction flask and the mixture was cooled to 0°C under stirring. 41 g of Zinc oxide and 7 g of Zinc chloride were added under stirring. Subsequently, 106.5 g of butanoyl chloride was added to the above mixture in 4 hours maintaining the temperature of the reaction medium between 0°C and 5°C under stirring. The reaction medium was stirred for another 1 hour until the acylation reaction was substantially completed. The reaction mass was subjected to aqueous workup to remove Zinc chloride and butanoic acid and the organic layer was separated and distilled to recover 65 g of unreacted 1,3-benzodioxole and 75 g of l-(l,3-benzodioxol-5-yl)-l-butanone with a GC purity of > 99%. The l-(l,3-benzodioxol-5-yl)-l-butanone was subjected to selective reduction and dehydration as discussed in Example 2 to obtain 66 g of 5-butyl-l,3-benzodioxole with a yield of 115.8% (wt./wt. on 1,3-benzodioxole consumed) and purity of > 99% by GC analysis.
Example 8
[0079] Preparation of 6-propyl-l,4-benzodioxane (using 0.5 moles of Zinc oxide and 0.05 moles of Zinc chloride per mole of acyl chloride using dichloromethane as solvent)
[0080] 136 g of 1 ,4-benzodioxane and 190 g of dichloromethane were charged into a 1 litre reaction flask and the reaction mixture was cooled to 0°C under stirring. 41 g of Zinc oxide and 7 g of Zinc chloride were added under stirring. Subsequently, 92.5 g of propionyl chloride was added in 4 hours maintaining the temperature of the reaction medium between 0°C and 5°C under stirring. The reaction medium was stirred for another 1 hour till the acylation reaction was substantially completed. The reaction mass was subjected to aqueous workup to remove Zinc chloride and propionic acid and the organic layer was separated and distilled to recover 85 g of unreacted 1 ,4-benzodioxane and 62 g of ethyl enedioxybenzene propiophenone with a GC purity of > 99%. The ethyl enedioxybenzene propiophenone was subjected to selective reduction and dehydration as discussed in example 2 to obtain 53 g of 6-propyl-l,4-benzodioxane with a yield of 104% (wt./wt. on 1 ,4-benzodioxane consumed) and purity of > 99% by GC analysis.
[0081] Any embodiments which could be reached by the motivation or teachings of the specification of this invention, but not explained by this specification will fall within the scope of this invention.
ADVANTAGES OF THE INVENTION
[0082] The present disclosure provides process(es) to overcome the problems associated with conventional process(es) for the acylation of alkylenedioxybenzene compound(s). [0083] The present disclosure provides a process for the acylation of alkylenedioxybenzene compounds without substantial degradation of the alkylenedioxybenzene or acylated products formed therefrom.
[0084] The present disclosure provides a process for the acylation of alkylenedioxybenzene compounds that substantially reduces the amount of Lewis acid, such as Zinc chloride, required as catalyst.
[0085] The present disclosure provides a process for the acylation of alkylenedioxybenzene compounds to obtain the acyl compound of Formula IV in high yield (greater than 100% wt./wt. on the alkylenedioxybenzene consumed).
[0086] The present disclosure provides a process for the acylation of alkylenedioxybenzene compounds to obtain the acylated product of Formula IV with high purity (greater than 99% by GC analysis).
[0087] The present disclosure provides an efficient process for preparation of alkyl and alkylene derivatives of alkylenedioxybenzene compounds without substantial degradation of any of the starting compound(s) and the desired product during the course of reaction.

Claims

We Claim:
1. A process for preparation of compound of Formula IV, said process comprising the step of reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent,
Figure imgf000024_0001
Formula TV Formula II Formula III wherein Rl, R2 and R3 independently represent H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R) group, wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; and n= 1, 2, 3, 4, 5, 6, 7 or 8;
characterized in that the step of reacting the alkylenedioxybenzene compound of Formula II with the acyl halide of Formula III is effected in presence of at least one amphoteric oxide and preferably one Lewis acid, and further characterized in that the in-situ quenching of compound of formula H-X formed during the course of the reaction is effected, so as to substantially eliminate degradation of the compounds of Formula Γν and Formula II.
2. The process as claimed in claim 1, wherein said amphoteric oxide is selected from a group consisting of Zinc oxide, Tin oxide, Aluminum oxide, Beryllium oxide, and mixtures thereof, and wherein the amphoteric oxide is used in a quantity ranging from about 0.2 moles to about 0.9 moles per mole of acyl halide.
3. The process as claimed in claim 2, wherein the amphoteric oxide selected is Zinc oxide, and wherein Zinc oxide is used in a quantity ranging from about from about 0.4 moles to about 0.6 moles per mole of acyl halide.
4. The process as claimed in claim 1, wherein said Lewis acid is selected from a group consisting of Zinc chloride, Tin chloride, Aluminum Chloride, Beryllium chloride, and mixtures thereof, and wherein the Lewis acid is used in a quantity ranging from 0.0 moles to about 0.5 moles per mole of acyl halide.
5. The process as claimed in claim 4, wherein said Lewis acid is Zinc chloride, and wherein Zinc chloride is used in a quantity ranging from about 0.01 moles to about 0.25 moles per mole of acyl halide, and more preferably from about 0.01 moles to about 0.1 moles per mole of acyl halide.
The process as claimed in claim 1, wherein said solvent is selected from the group consisting of dichloromethane, ethylene di chloride, 1,2-dichloropropane, or mixtures thereof.
The process as claimed in claim 6, wherein said solvent is dichloromethane.
8. A process for preparation of a compound of Formula IA, said process comprising the steps of:
(a) obtaining a compound of Formula IV by reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent,
Figure imgf000025_0001
Formula IV Formula II Formula III
wherein Rl, R2 and R3 independently represents H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R), wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; and n= 1, 2, 3, 4, 5, 6, 7 or 8; and
(b) effecting selective reduction followed by dehydration of the compound of Formula IV to obtain the compound of Formula IA;
Figure imgf000026_0001
Formula IA
wherein Rl, R2 and R3 independently represents H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R), wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; and n= 1, 2, 3, 4, 5, 6, 7 or 8;
characterized in that the reaction of said alkylenedioxybenzene compound of Formula II with said acyl halide of Formula III is effected in presence of at least one amphoteric oxide and preferably one Lewis acid, and further characterized in that the in-situ quenching of compound of formula H-X formed during the course of the reaction is effected, so as to substantially eliminate degradation of the compounds of Formula Γν and Formula II.
9. A process for preparation of a compound of Formula IB, said process comprising the steps of:
(a) obtaining a compound of Formula IV by reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent,
Figure imgf000026_0002
Formula IV Formula II Formula III wherein Rl, R2 and R3 independently represents H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R), wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; and n= 1, 2, 3, 4, 5, 6, 7 or 8; and
(b) reacting the compound of Formula IV with hydrogen gas in presence of a composite catalyst comprising a Nickel catalyst and an acid catalyst to obtain the compound of Formula IB;
Figure imgf000027_0001
Formula IB
wherein Rl, R2 and R3 independently represents H, linear or branched CI - CIO alkyl or alkenyl group, or alkoxy (-0-R), wherein R is selected from linear or branched alkyl group with carbon atoms ranging from CI to C6; m = 1, 2, or 3; and n= 1, 2, 3, 4, 5, 6, 7 or 8;
characterized in that the reaction of said alkylenedioxybenzene compound of Formula II with said acyl halide of Formula III is effected in presence of at least one amphoteric oxide and preferably one Lewis acid, and further characterized in that the in-situ quenching of compound of formula H-X formed during the course of the reaction is effected, so as to substantially eliminate degradation of the compounds of Formula Γν and Formula II.
10. The process as claimed in claim 10, wherein said Nickel catalyst is Raney Nickel.
11. The process as claimed in claim 10, wherein said acid catalyst is selected from a group consisting of p-toluene sulfonic acid, anhydrous Sodium bisulphate, anhydrous Potassium bisulphate, Nickel chloride, Ferrous sulphate, Zinc chloride or mixtures thereof.
12. The process as claimed in claim 10, wherein said compound of Formula IB is dihydrosafrole of Formula VII.
Figure imgf000028_0001
27
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