FIELD OF THE INVENTION

[0001] The present disclosure is in the field of organic synthesis and relates to a process for preparation of (E)- 1 -Methoxy-4-(prop- 1 -en- 1 -yljbenzene. More particularly, the present disclosure relates to an improved process for isomerization of (Z)-l-Methoxy-4-(prop-l-en-l- yl)benzene to (E)- 1 -Methoxy-4-(prop- 1 -en- 1 -yljbenzene.

BACKGROUND OF THE INVENTION

[0002] 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.

[0003] Anethole also known as anise camphor or isoestragole, can be in two isomeric forms, cis and trans, in which trans-anethole finds application in a wide variety of industries including food and beverage industries, and in the formulation of oral hygiene products. (Z)-l-Methoxy-4- (prop-l-en-l-yl)benzene commonly known as cis-anethole, and (E)- 1 -Methoxy-4-(prop- 1 -en- 1 - yl)benzene commonly known as trans-anethole. Anethole is a valuable intermediate for the synthesis of pharmaceutical compounds and perfumery chemicals. Anethole is also used as starting material for the manufacture of anisic aldehyde. Likewise, it is also used in color photography; as a sensitizer in color bleaching processes; in perfumes, particularly as an additive to toothpastes as well as to cosmetic preparations; as a flavor for liqueurs and as a flavor for licorice candies. Most of the anethole which is used in this respect is extracted from natural sources, it being a main component of many essential oils such as pine oil, anise oil, fennel anise star oil, or in anise seed. However, the natural sources are subject to varying conditions in nature and therefore shortages of the natural sources may develop during a period of time. In order to overcome these shortages and not be dependent upon a natural crop, some routes for the synthetic preparation of anethole have been developed. [0004] Russian patent SU496262 describes isomerization of cis-anethole by heating at 180° in presence of 0.2-7% of catalyst MHSO4 (where M is alkali metal or NH ₄₎ , resulting in 15% cis- and 85% trans-anethole conversion. Inventors of this Russian patent also published a research paper in journal Maslozhirovaya Promyshlennost, 2, 29-31, 1976, which also describes that L1HSO4, NaHS0 ₄ .H ₂ 0, NH4HSO4, and KHSO4 catalyzed the isomerization of c/.v-anethole to give 82: 18, 80:20, 87: 13, and 85: 15 trans:cis conversion ratios, respectively. Both these references hereinafter referred to as conventional prior art.

[0005] United States Patent US2052745 relates to a purification process of anethole by isomerization of methyl chavicol by washing the isomerized product with dilute alkaline solutions and removing the alkali by successive washings with water.

[0006] Russian patent SU 455087 describes isomerization of cis-anethole to trans-anethole at l00-200°C in a soln. containing a salt (or complex) of a Group VIII metal with alcohols or alkali alcoholates.

[0007] Journal Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, Issue 6, 1428-30, 1975 describes optimum conversion of cis-anethole under a number of different sets of conditions, e.g., 0.01 mole Fe(CO)5/mole anethole at l00°C for 0.5 hr leads to 9% cis- and 91% trans anethole. The cis-trans isomerization of anethole in the presence of homogeneous catalysts, e.g., (PhCN) ₂ PdCl ₂ , (Ph ₃ P) ₃ RhCl, Li ₂ PdCl ₄ , (Ph ₃ P) ₃ RuHCl, H ₂ PtCl ₆ , or Fe(CO) ₅ were studied.

[0008] United States Patent US4038325 describes a process for the isomerization of cis- anethole to trans-anethole which comprises treating cis-anethole with rhodium salts like rhodium chloride, rhodium bromide, rhodium iodide, rhodium nitrate, rhodium sulfate, rhodium formate, rhodium acetate, rhodium propionate, rhodium butyrate or rhodium acetylacetonate in an alcoholic medium at a temperature in the range of from about 25 °C to about 200°C and a pressure in the range of from about atmospheric to about 100 atmospheres, and recovering the resultant isomerized trans-anethole.

[0009] It is essential that the trans-anethole, which is used as a flavoring agent should have satisfactory organoleptic properties. During manufacturing of trans-anethole some amount (5- 6%) of undesired cis-anethole also forms. This cis-anethole deteriorates olfactory profile of trans-anethole. Cis-anethole and a variety of other process impurities adversely affect the taste and odor of the trans-anethole. So there is a need to recover cis-anethole and isomerize it into desired trans-anethole. To produce an organoleptically acceptable trans-anethole virtually all of the impurities must be removed or substantially reduced in concentration (i.e. <1.0% total impurities).

[00010] From a commercial point of view, several methodologies have been reported to isomerize cis-anethole to trans-anethole, nevertheless they are not economically viable and environment friendly because of formation of high boiling impurities (sometimes up to 20-40%) during isomerization, which results in excess residue formation and also reduces the yield and purity of trans-anethole. None of the prior art references teaches how to reduce or suppress the formation of high boiling impurities.

[00011] Generally pure cis-anethole is having around 98% cis-isomer, 0.5% trans-isomer and around 1-2% other impurities such as acidic and phenolic compounds. These acidic and phenolic compounds accelerate the rate of polymerization of anethole during isomerization. For example when anethole containing these impurities was exposed to air, polymerization took place and in a few minutes crystals of the polymer could be seen. Even after subjecting the anethole to a very carefully controlled fractional distillation these undesirable constituents were still present in enough concentration to be objectionable. This parallel polymerisation reaction reduces the yield of trans-anethole and makes the traditional isomerization process commercially unviable. So, there is a need to develop an isomerization process to convert cis-anethole to trans-anethole in such a way, which restricts the formation of high boiling polymers and enhances the isolated yield of trans-anethole.

[00012] It has been also observed that in known conventional prior art method of isomerization of cis-anethole to trans-anethole, at around 50-60% conversion, a thermodynamic equilibrium establishes and due to that further isomerization stops. In that situation, if reaction continues, it does not increase the quantitative yield of trans-anethole, but initiates the polymerisation reaction, which is not desired. An increase in the amount of catalyst also does not increase the degree of conversion and the composition of the reaction mixture.

[00013] A number of other drawbacks are also associated with the conventional prior art procedures, e.g.: (i) poor conversion, (ii) excess quantity of residue wastes generated makes the process environmentally unviable, (iii) poor selectivity, (iv) economically unviable because of low yield, (v) presence of polymerized side products which results in higher toxicity and unpleasant odour and taste. [00014] Increasing industrial demand has also made it necessary to develop an improved process for isomerization of cis-anethole to trans-anethole. The present disclosure satisfies the existing needs, as well as others, and generally overcomes the deficiencies found in the prior art.

[00015] All publications herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.

[00016] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and/or patentability.

OBJECTS OF THE INVENTION

[00017] It is an object of the present disclosure to provide a new and improved process for isomerization of cis-anethole to trans-anethole.

[00018] It is another object of the present disclosure to provide an economically viable process for isomerization of cis-anethole to trans-anethole, which restricts formation of high boiling impurities.

[00019] It is another object of the present disclosure to provide a method to minimize or eliminate undesirable polymerization side reactions during isomerization of cis-anethole.

[00020] It is another object of the present disclosure to prepare substantially pure organoleptically acceptable trans-anethole in a stable form.

[00021] It is yet another object of the present disclosure to provide an improved process which enables rapid and efficient isomerization of cis-anethole to trans-anethole in high quantitative isolated yield.

[00022] Other and further objects of this disclosure will be apparent from the following detailed description and appended claims which form a part of this specification.

SUMMARY OF THE INVENTION [00023] In order to accomplish one or more of the above objects, the present disclosure provides a new and improved process for preparation of trans-anethole from a corresponding cis- anethole, which includes isomerization of cis-anethole in presence of a bisulfate salt and a tertiary amine. The present disclosure comprises a simple, highly selective and economically viable catalytic process, whereby cis-anethole can be substantially isomerized to trans-anethole in high yields.

[00024] According to embodiments of the present disclosure, the disclosed process for preparation of trans-anethole can include the steps of: combining cis-anethole, a bisulfate salt and a tertiary amine to form a reaction mixture; heating the reaction mixture at an elevated temperature to cause isomerization of the cis-anethole to trans-anethole; and isolating the trans anethole.

[00025] In an embodiment, the bisulfate salt that can be used in the process of the present disclosure can have the formula MHSO ₄ , wherein M can be Na, K or NH ₄ . Satisfactory results can be achieved by employing a weight ratio of cis-anethole to bisulfate salt in the range of from 1:0.01 to 1: 10, more preferably from 1 :0.05 to 1:0.1.

[00026] In another embodiment, the tertiary amine that can be used in the process of the present disclosure can have the formula R ₃ N or (R-OH) ₃ N, wherein R can be - C ₁₀ alkyl group. In certain preferred embodiments, the tertiary amine can be selected from the group consisting of triethylamine, trimethylamine, tributylamine, triethanolamine, N- propyldioctylamine, N,N-diisopropylethylamine, tripentylamine, tri-n-octylamine, N,N- diethyldecanamine, N-methyldioctylamine, N-methyl-N-octyl-l-decanamine, N-ethyl-N-methyl- l-octanamine N,N-dimethylpentylamine and a combination thereof. Satisfactory results can be achieved by employing a weight ratio of cis-anethole to tertiary amine in the range of from 1:0.0001 to 1:0.1, preferably from 1:0.0001 to 1:0.01, more preferably from 1:0001 to 1:0.001.

[00027] Various objects, features, aspects and advantages of the inventive subject matter will become more apparent from the following detailed description of preferred embodiments.

DETAILED DESCRIPTION OF THE INVENTION

[00028] The following is a detailed description of embodiments of the disclosure. 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.

[00029] 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.”

[00030] 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.

[00031] As used in the description herein and throughout the claims that follow, the meaning of“a,”“an,” and“the” includes plural reference unless the context clearly dictates otherwise. Also, as used in the description herein, the meaning of“in” includes“in” and“on” unless the context clearly dictates otherwise.

[00032] In some embodiments, the numbers expressing quantities of ingredients, properties such as concentration, process conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in some instances by the term“about.” Accordingly, in some embodiments, the numerical parameters set forth in the written description are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable.

[00033] The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. [00034] All methods described herein can be performed in suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g.“such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.

[00035] The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments.

[00036] As used herein, the term“flavoring substance” refers to the chemicals used for flavoring food products.

[00037] The present disclosure is directed to a new and improved process for isomerizing cis- anethole to trans-anethole. The disclosed isomerization process is simple, highly selective and economically viable catalytic process, which can enable rapid and substantial conversion of cis- anethole to its trans-isomer in high yields. In a broad aspect, the present disclosure provides a process for preparing trans-anethole of formula I from a corresponding cis-anethole of formula II, which includes isomerizing cis-anethole of formula II in presence of a bisulfate salt and a tertiary amine as catalysts.

Formula I Formula II

[00038] According to embodiments of the present disclosure, the disclosed process for preparation of trans-anethole can include the steps of: combining cis-anethole, a bisulfate salt and a tertiary amine to form a reaction mixture; heating the reaction mixture at an elevated temperature to cause isomerization of the cis-anethole to trans-anethole; and isolating the trans anethole. [00039] In various embodiments, a reaction mixture comprising cis-anethole, a bisulfate salt and a tertiary amine can be heated at an elevated temperature which can be a reflux temperature of the reaction mixture, to cause isomerization of the cis-anethole to trans-anethole.

[00040] In certain preferred embodiments, the isolation step can include cooling of the reaction mixture to a temperature in the range of from l0°C to 35°C, and separating the cooled reaction mixture into an organic phase containing trans- anethole and an aqueous phase. Thus obtained organic phase can be subjected to fractional distillation to obtain pure trans-anethole.

[00041] In an embodiment, the bisulfate salt that can be used in the process of the present disclosure can have the formula MHSO ₄ , wherein M can be Na, K or NH ₄ . Preferably, the bisulfate salt can be selected from the group consisting of potassium bisulfate, sodium bisulfate, ammonium bisulfate and a combination thereof. Satisfactory results can be achieved by employing a weight ratio of cis-anethole to bisulfate salt in the range of from 1:0.01 to 1: 10, more preferably from 1:0.05 to 1:0.1.

[00042] In another embodiment, the tertiary amine that can be used in the process of the present disclosure can have the formula R ₃ N or (R-OH) ₃ N, wherein R can be Ci - C ₁₀ alkyl group. Preferably, the tertiary amine can be selected from the group consisting of triethylamine, trimethylamine, tributylamine, triethanolamine, N-propyldioctylamine, N,N- diisopropylethylamine, tripentylamine, tri-n-octylamine, N,N-diethyldecanamine, N- methyldioctylamine, N-methyl-N-octyl-l-decanamine, N-ethyl-N-methyl-l-octanamine N,N- dimethylpentylamine and a combination thereof. Satisfactory results can be achieved by employing a weight ratio of cis-anethole to tertiary amine in the range of from 1:0.0001 to 1 :0.1, preferably from 1:0.0001 to 1:0.01, more preferably from 1:0001 to 1 :0.001.

[00043] In one embodiment, the cis-anethole used in the process of the present disclosure can have cis-isomer fraction in the range of from 50% to 99%.

[00044] According to embodiments of the present disclosure, the disclosed isomerization process can limit formation of undesired high boiling impurities to 3-7%, as compared to conventional processes where formation of undesired high boiling impurities is 15-30%, as determined by gas chromatographic analysis.

[00045] In various embodiments, the disclosed isomerization process can enable 90% to 92% conversion of cis-anethole to trans-anethole when the cis-anethole is isomerized in presence of a mixture of a bisulfate salt and a tertiary amine (GC area %: 72-78% trans-anethole, 15-18% cis- anethole and 3-7% high boiling and other impurities), while the conventional prior art processes which employ only bisulfate salt as catalyst provide 70% to 75% conversion of cis-anethole to trans-anethole (GC area %: 60-65% trans-anethole, 10-15% cis-anethole and 15-30% high boiling and other impurities). According to embodiments, unisomerized cis-anethole left in the reaction mixture can readily be recovered in distillation and thereafter employed in the preparation of other batches of trans-anethole.

[00046] According to embodiments of the present disclosure, the disclosed isomerization process can provide 15-20% extra yield of the trans-anethole final product, as compared to conventional prior art processes, by suppressing unwanted polymerization side reactions which are common in conventional processes and typically lead to formation of undesired polymer compounds (high boiling impurities).

[00047] In various embodiments, trans-anethole of formula I produced in accordance with the process disclosed herein can have a purity greater than 97%, more preferably greater than 99.5% as determined by GC.

[00048] While the foregoing description discloses various embodiments of the disclosure, other and further embodiments of the disclosure may be devised without departing from the basic scope of the disclosure. The disclosure is not limited to the described embodiments, versions or examples, which are included to enable a person having ordinary skill in the art to make and use the disclosure when combined with information and knowledge available to the person having ordinary skill in the art.

EXAMPLES

[00049] The present disclosure is further explained in the form of following examples. However, it is to be understood that the foregoing examples are merely illustrative and are not to be taken as limitations upon the scope of the disclosure. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the disclosure.

Example 1: Method of preparing trans -anethole

[00050] In a vessel, charge c/.v-anethole (lOOg) (GC purity: 98.53%). Add potassium bisulfate (7.5g) and triethylamine (0.05g) at room temperature. Raise the temperature of the reaction mixture and reflux for 7-8hrs. Monitor the reaction on GC (GC results shows 78.3% trans- isomer, 16.1% cts-isomer, 5.6% high boiling and other impurities). Cool the reaction mass to 25- 30°C. Separate the organic layer to get crude product. The crude product purified by distillation, which gives pure trans-anethole (Yield: 73.5 g; GC purity: 99.5%) and 15.8 g recovered cts- Anethole. Recovered cts-anethole is recycled in further batches for isomerization.

Example 2: Method of preparing trans -anethole

[00051] Follow the same procedure as described in Example- 1 but using triethanolamine (0.05g) in place of triethylamine. GC results shows following conversion: 76.8% trans- isomer, 17.2% cts-isomer, 5.9% high boiling and other impurities. Yield: 72.3 g; GC purity: 99.6% and recovered cis- Anethole: 16.1 g. Recovered cts-anethole is recycled in further batches.

Example 3: Method of preparing trans -anethole

[00052] Follow the same procedure as described in Example- 1 but using N,N- diisopropylethylamine (0.05g) in place of triethylamine. GC results shows following conversion: 75.2% trans- isomer, 17.9% cts-isomer, 6.8% high boiling and other impurities. Yield: 71.5 g; GC purity: 99.5% and recovered cts-Anethole: 16.5 g. Recovered cts-anethole is recycled in further batches.

Reference Example 1: Method of preparing tran -anethole according to conventional prior art method

[00053] In a vessel, charge cts-anethole (lOOg) (GC purity: 98.53%). Add potassium bisulfate (7.5g) at room temperature. Raise the temperature of the reaction mixture and reflux for 7-8hrs. Monitor the reaction on GC. (GC results shows 63.1% trans- isomer, 10.7% cts-isomer, 26.1% high boiling and other impurities). At this stage, if reaction continues to get optimum conversion of 70-75%, only high boiling impurities increases instead of getting more trans- isomer. So cool the reaction mass to 25-30°C. Separate the organic layer to get crude product. The crude product purified by distillation, which gives pure trans-anethole (Yield: 46.8 g; GC purity: 98.5%) and 7.3 g recovered cis- Anethole. Recovered cts-anethole is recycled in further batches. [00054] The numerical values of various parameters given in the specification are at approximations and slightly higher or slightly lower values of these parameters fall within the ambit and the scope of the disclosure.

[00055] While considerable emphasis has been placed herein on the specific steps of the preferred process, it will be highly appreciated that many steps can be made and that many changes can be made in the preferred steps without departing from the principles of the disclosure. These and other changes in the preferred steps of the disclosure will be apparent to those skilled in the art from the disclosures herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation.

[00056] The process according to the present disclosure can have various advantages, such as:

i) The present disclosure provides a process for isomerization of cis-anethole that suppresses unwanted side reactions, thereby resulting in less formation of unwanted polymeric compounds (high boiling impurities).

ii) The present disclosure provides a process for isomerization of cis-anethole that gives less quantity of residue in the range of 3-7% in contrast to 15-30% (as in the conventional prior art method) after fractional distillation at large commercial scale, and thereby supports more environment friendly process.

iii) The present disclosure provides a process for isomerization of cis-anethole that results in relatively high yield of trans-anethole final product with optimum purity at commercial scale.

iv) The present disclosure provides a process for isomerization of cis-anethole, where unconverted cis-anethole is recovered and recycled in further isomerization batches. v) The present disclosure provides a process for isomerization of cis-anethole wherein recovered catalyst is recycled.

vi) The present disclosure provides a process for isomerization of cis-anethole that provides lower impurity profile in final product, as mild reaction condition restricts the formation of undesired impurities.

vii) The present disclosure provides a process for isomerization of cis-anethole that is simple, safe, time saving and having convenient operational steps at commercial scale. viii) The present disclosure provides a process for isomerization of cis-anethole that saves utility at commercial scale because of simple work-up and product isolation procedure. ix) The present disclosure provides a process for isomerization of cis-anethole that improves productivity and equipment utilization at commercial scale.

x) The present disclosure provides a process for isomerization of cis-anethole that is economic and environment friendly.

xi) The present disclosure provides a process for isomerization of cis-anethole that has better isomeric selectivity as compared to conventional prior art technology.