Title of Invention

AN IMPROVED PROCESS FOR THE PRODUCTION OF THYMOL

Abstract

An improved process of preparation of thymol which conprises reacting cyclic terpene ketones of the kind as herein described , over a novel catalyst comprising metals from group VIII and group IB in a solid support such as herein desribed, in presence of a solvent or a diluent, at a temperature in the range of 120 to 600° C, under hydrogen atmosphere at a pH in the range of 4 to 12, for a period in the range of 24 to 360 hr, recovering and purifying the product by conventicmal methods, the process is characterized in using the novel catalyst as defined above.

Full Text

The present invention relates to an improved process for the production of thymol. The invention particularly relates to an improved vapour phase process for the production of thymol. More particularly this invention relates to the direct oxidation/ dehydrogenation/ aromatization of cyclic terpene ketones like menthone, isomentone and mixture of menthone-isomenthone from any source such as Mentha arvensis oil, piperitone and pulegone and of essential oils containing these compounds in a single step over highly active and selective catalysts and noble metal catalysts under continuous vapour phase process into thymol without any side reactions, in varied solvent media under optimum conditions of temperature, pressure, pH and time to get thymol of high purity which is distilled from the unreacted menthone and other cyclic terpene ketones and further purified by redistillation and crystallization for the recovery of pharmaceutical grade thymol of natural thyme aroma. Thymol, C10H14O , M+ 150.22, mp. 50.5 - 51.5 °C, bp. 233 -234° C, d25 0.9699 is a crystalline solid of intensely spicy odour and taste, characteristic of ajowan seeds. Thymol occurs naturally in various essential oils and is the chief constituent of ajowan and thyme oils. Menthone, C10H18O, M+ 154.25, bp. 207° C, d25 0.895 and isomenthone, C10Hi8O, M+154.25, bp. 210° C, d25 0.896; occur naturally in various essential oils, particularly of Mentha species. In inventing the present process, the advantage has been taken of the fact that in recent years, India has emerged as a major producer of Mentha arvensis oil (15,000-20,000 tons/year) containing 15- 20% of menthone- isomenthone in addition to menthol (70-80%) and other compounds. After separation of menthol by crystallization, the dementholised oil rich in menthone/ isomenthone is available in large amounts as a low cost industrial bye product, from which menthone-isomenthone (2200-3000 tons/annum) can be separated for the production of other useful chemicals. The additional quantities of menthone-isomenthone are also available world over. Small amount of menthone and dementholised oil is used as such in flavour industry. In such cases dementholised oil is usually rectified by distillation to obtain concentrates of individual terpenes or group of terpenes such as terpene hydrocarbons, menthone-isomenthone mixture, menthol isomers and high boilers. Industrially thymol is produced mostly by distillation of natural essential oils [Guenther, E. (1949), The Essential oils]. The conventional methods involve separation of thymol by crystallization and fractional distillation of ajowan oil (oil of Trachyspermum ammi) and some other oils ( oil of monards, Monarda punctate, thyme oil, Thymus vulgaris and oil of Ocimum viride). Thymol is also being produced synthetically from m- cresol and P-cymene [W. Forest, (1963) Newer Methods of Preparative Organic Chemistry Vol. II, p.344, 304]. Thymol obtained by the oxidation of p-cymene is usually contaminated invariably with source impurities along with small amount of carvacrol formed during the oxidation at 2-position. Thymol obtained from m- cresol usually is contaminated with source petroleum impurities and some other side products, which impart off flavour to it, hence don't command high value. Catalytic and chemical dehydrogenation and disproportionation of menthone and piperitone in liquid phase has been attempted by several workers using noble metals [RRL, News Lett. (1989),16(2) 8.], sulphur, ferric chloride, selenium dioxide, chlorine and bromine under acidic/ basic conditions, and also copper and other catalysts [Agarwal et al., (1982) Ind. J. Chem., 21B, 545; J. March, (1992), Aromatization of Six membered rings. In: Advanced Organic Chemistry (4th ed.) Academic Press; House et al. J.A.C.S.(1989) 111,5970; A. Jenson et al Compt. Rend.(1957) 245,183; Chopra et al Ind. Perf. (1973) 17(2), 69; Croft et al Tetrahedron. (1981) 37(2), 383]. Most of these dehydrogenation are of academic interest for want of low yield and side reactions. No concrete information is available in the literature for thequantitative conversion of menthone, isomentone and mixture of menthone-isomenthone (ex Mentha arvensis oil or from any other source), piperitone and pulegone and of essential oils containing these compounds into thymol, hence the necessity for development of such a process. Some of the processes mentioned above are even employed on a commercial scale but suffer due to side reactions and are accompanied with undesirable side products above tolerable limits, which are difficult to separate economically. These processes are also time consuming and are quite complicated. The present invention provides a catalytic process to convert cyclic terpene ketones like menthone-isomenthone into thymol in quantitative yield without side reactions along with the separation of thymol of high purity from starting materials. No prior art is available in the literature concerning the present invention. Therefore, invention of a direct and economical oxidation/ dehydrogenation/ aromatization process for conversion of cyclic terpene ketones like menthone-isomenthone into thymol in a single step without side reactions is advantageous. Further, the starting material being a natural oxygenated monoterpenoid at required position, the final product is of high flavour and pharmaceutical value and is free from impurities like carvacrol and obnoxious coal tar bye odours. The main objective of the present invention is to provide an improved process for the production of thymol from cyclic terpene ketones which obviates the drawbacks of the present methods as detailed above. Another objective of the present invention is to develop the direct process for the oxidation/ dehydrogenation/ aromatization of cyclic terpene ketones like menthone, isomenthone and mixture of menthone-isomenthone from any source such as Mentha arvensis oil, piperitone and pulegone and of essential oils containing these compounds in a single step over a novel highly active and selective supported metal atom dispersed catalysts and noble metal catalysts under continuous vapour phase process into thymol without any side reactions, in varied solvent media under optimum conditions of temperature, pressure, pH and time to get thymol of high purity which is distilled from the unreacted menthone and other cyclic terpene ketones and further purified by redistillation and crystallization for the recovery of pharmaceutical grade thymol of natural thyme aroma. Yet another objective of the invention is to use a novel basic supported metal catalyst in such a way which will only oxidize and aromatize the cyclohexane ring without affecting the othe- part of the molecule so as to give the maximum yield of the product. Yet still another objective is that by employing the catalyst and the conditions mentioned in the invention, the formation of undesired side products is minimized. Accordingly the present invention provides an improved process of preparation of thymol which comprises reacting cyclic terpene ketones over a novel catalyst comprising metals from group VIII and group IB in a solid support such as herein described , in presence of a solvent or a diluent , at a temperature in the range of 120 to 600° C, under hydrogen atmosphere at a pH in the range of 4 to 12, for a period in the range of 24 to 360 hr, recovering and purifying the product by conventional methods , the process is characterized in using novel catalyst such as definedabove. In an embodiment of the present invention the cyclic terpene ketones used may be such as menthone , isomenthone , mixture of menthone and isomenthone from any source , piperitone and pulegone. The novel catalyst may be prepatred by the process as claimed in our co-pending application no. 636/del/99 . The method involve reacting sources of metals from group VIII and IB metals with or without promoters and initiators , in combination with alkali and alkali metal salts in a solvent at a temperature in the range of 0 - 100 ° C for a period in the range of 0.5 -2.5 hrs and mixing the above reaction mixture with solid support, removing the solvent and heating the residue obtained above at a temperature in the range of 160 - 600 ° C for a period in the range of 8 - 16 hrs. In another embodiment of the reaction the solvent or dilutent used may be gases such as nitrogen , oxygen , hydrogen , helium or liquids such as pyridine , decane , dodecane , hexadecane and substrate itself. In accordance with this invention we have found that in the presence of strong bases and in the presence of dehydrogenation catalyst, under pressure in reducing atmosphere , cyclic terpene ketones like menthone - isomenthone are converted partially into thymol without any side reactions. We have found that suitable catalyst comprise a class consisting of highly active and selective supported metal atom dispersed catalyst at suitable temperature applied under conditions of dehydrogenation in the presence of hydrogen above atmospheric pressure. First class of catalysts comprises materials which are essentially simple or complex noble metal salts and supported noble metals which are suitably used in the media either as such or in combination with alkali and alkaline metal hydroxides and oxides and phase transfer medium . The second class of catalyst comprises supported metal atom dispersed catalyst consisting of metals from group VIII and group IB . In some cases combination of metals reacts readily with above type of organic compounds. In other cases the reaction is so sluggish that it is desirable to use a promoter or initiator to speed up the reaction between catalyst and ketones. Metals of group VI and VIIB may act as promoters. Nickel and cobalt are important hydrogenation and dehydrogenation catalysts because of their ability to chemisorb hydrogen. Raney Nickel is one of the most important catalysts of nickel and is used widely in laboratory and industrial hydrogenation and dehydrogenation processes. It is the most active and the least specific nickel catalyst and also has been used in continuous hydrogenation processes but is not suitable for continuous dehydrogenation processes. The activity and specificity of nickel catalyst is also very much dependent upon its method of preparation and other parameters of temperature, time and mode of addition. A variety of nickel catalysts are available which are used for specific purposes. The dehydrogenation of cyclic terpene ketones in the presence of Raney Nickel is a complex process and mixture of atleast three products viz, aromatic alcohols, unsaturated alcohols and saturated alcohols, may well be obtained. In general, mild conditions lead to a predominance of saturated alcohols whilst more forcing conditions favour the aromatic alcohols. Raney Nickel in general, cannot be used directly for the dehydrogenation of ketonic function in presence of isolated olefinic centers because of its activity to hydrogenate such centers which acts as hydrogen acceptors. It is therefore, required to modify the catalyst in such a way that restricts its hydrogen acceptor activity and disproportionation reactions. It is, therefore, the purpose of this invention to devise a suitable metal catalyst which could dehydrogenate the cyclic terpene ketones only without hydrogenating the molecule. The process of production of thymol comprises of the direct oxidation/ dehydrogenation/ aromatization of cyclic terpene ketones like menthone, isomentone and mixture of menthone-isomenthone (ex Mentha arvensis oil or from any other source), piperitone and pulegone - and of essential oils containing these compounds in a single step over highly active and selective supported metal atom dispersed novel catetlysts vmder continuous vapour phase process into thymol without any side reactions, vmder conditions of dehydrogenation in varied solvent media if desired, under optimum conditions of temperature in the range of 120 to 600 °C, under pressure of hydrogen and nitrogen in the range of 15 to 100 psi, pH in the range of 4 to 12, and time in the range of 24 to 360 hr to get thymol of high purity, which is distilled from the vmreacted menthone and other cyclic terpene ketones and further purified by conventional redistillation and crystallization for the recovery of pharmaceutical grade thymol of natural thyme aroma. We have found that although noble metal and metal atom dispersed catalyst (Fe, CO, Ni) give dehydrogenated products more or less in good amounts but the selectivity and yields were more pronounced in favour of thymol when the catalysts were supported on inert, basic and neutral supports like, alumina, silica gel, ceramics, kieselguhr, bentonite, Askansk clay, Askonite etc. Depending on the system selected, the catalysts can be preformed and packed in a column of suitable length and diameter and then menthone-isomenthone mixture is passed through at suitable pressure and temperature without affecting continuous flow of feed and solvent gases. In general the usual relationship of time, temperature, and amount or activity of catalyst apply in the present case. Preferred temperatures range from 120°C to 600°C. At lower temperature reaction tends to be slow unless a high ratio of catalyst to reaction mixture is utilized. At above 600°C, the thermal decomposition of cyclic terpene ketones and thymol to other hydrocarbons and substituted phenols becomes an increasingly serious side reaction. We have found that the most suitable catalyst for the present inventions comprises of a class consisting of highly active and selective supported nickel type metal atom dispersed catalyst at suitable temperature applied under conditions of dehydrogenation in the presence of hydrogen above atmospheric pressure. In some cases mineral acids, inorganic and organic bases, salts of Group I, Group II and Group VII metals are used as modifiers to retard or check the hydrogenation of isolated olefinic centers. In general the usual relationship of catalyst activity, temperature, pressure, medium and time, along with other physical and chemical parameters apply in the present case. It is important to optimize all the above mentioned conditions in order to get the desired product. The above mentioned catalyst was also employed for various other cyclic terpene ketones. In every case aromatic alcohols were obtained without any side reactions and isolated olefins also isomerized under the reaction conditions employed. The thermally treated mixture is suitably rectified in batch fractionating column or a series of fractionating columns, separating thymol as a technically pure high boiling fraction. The light boiling menthone fraction was recovered as a technically pure material suitable for recycling to the step in which it is dehydrogenated to thymol. The high boiling technically pure thymol fraction is further purified by refractionation/ crystallization to afford thymol of superior flavour and pharmaceutical grade. In our copending application have described and claimed a process for the preparation and development of new supported metal atom dispersed catalyst for the oxidation of cyclic ketones into corresponding phenols and related compounds like thymol from menthone using the process described herein this application. The invention is described further with reference to examples given below. The example should not be construed as to restrict the scope of the invention. Example 1 Preparation of menthone and isomenthone: To the reboiler of 25 mm x 100 cm. fractionating column packed with protruded packing was charged 900 ml of dementholised oil (obtained from Mentha arvensis oil by removal of menthol by chilling process). The unit was operated under reduced pressure of 12 mm and elevated temperature of 90°C to remove terpene hydrocarbons and other low boiling fractions. The menthone rich fraction (95%purity , 370 ml) was collected at 120° C. Example 2 Conversion of menthone / isomenthone into thymol: To the reactor of 25 mm x 400 mm, fitted and loaded with a supported metal atom (Ni-Cu-Mn-support) dispersed catalyst (65g) prepared by the process as claimed in our copending application no. NF-293/98, menthone (100 ml) was added through sparge tube over a period of 1 hour, while maintaining temperature at 600°C under reducing atmosphere of nitrogen and hydrogen. GC analyses of the reaction product at the end of the reaction, confirmed the presence of thymol in the reaction product to the tune of 60%, which was distilled from the unreacted menthone and other cyclic terpene ketone and further purified by redistillation and crystallization for the recovery of pharmaceutical grade thymol of natural thyme aroma. Example 3 In a reactor 25mm x 400 mm Ni-Cu catalyst supported on Alumina-silica gel was loaded and sensitized in the hydrogen atmosphere at a temperature of 210 ° C . Isomenthone ( 60ml) was added through sparge tube over a period of 1 hour , while maintaining temperature at 240 0 C under nitrogen atmosphere . GC analyses of the reaction product confirmed the presence of thymol in the reaction product to the tune of 67% , which was processed by usual methods. Example 4 To the reactor of 25 mm x 400 mm , fitted and loaded with a supported metal atom( Ni-Co-Ag-support) dispersed catalyst ( 25 g) prepared by the process as claimed in our copending application no. 636 /del /99 , piperitone (100 ml) was added through sparge tube over a period of 3 hour , while maintaining temperature at 440 ° C under atmosphere of nitrogen and hydrogen . Gas chromatographic analysis of the reaction product at the end of the reaction , confirmed the presence of thymol in the reaction product at the end of the reaction , confirmed the presence of thymol in the reaction product to the tune of 66% , which was distilled from the unreacted piperitone and other cyclic terpene ketone and further purified by known methods. Example 5 To the reactor of 35mm x 100 cm , fitted and loaded with a supported metal atom ( Ni-Fe-Cu-Mn-support) dispersed catalyst ( 150 g) prepared by the process as claimed in our co-pending application no. 636/del/99 , pulegone ( 900 ml) was added through sparge tube over a period of 12 hours , while maintaining temperature at 360° C under atmosphere of hydrogen. Gas chromatographic analysis of the reaction product at the end of the reaction , confinned the presence of thymol in the reaction product to the tune of 68% . The reaction product (1.0 lit) was refluxed in a towers fractional distillation apparatus under reduced pressure. The light boiling menthone , isomenthone , pulegone or piperitone were recovered for recycling as first fraction . The later high boiling fraction on crystallization by chilling , provided technically pure thymol ( yield 56% ). Advantages 1. An improved one step process for the production of thymol from cyclic terpene ketones like menthone , isomenthone , piperitone and pulegone over highly active and selective supported metal atom dispersed catalyst. 2. The novel catalyst used in present invention which is bimetallic supported catalyst in nature i.e. catalyst containing group VIII and group IB metals is suitable under continuous vapour phase and batch process under elevated conditions of temperature and pressure. 3. An improved one step process for the production of thymol from cyclic terpene ketones without any side reactions. We Claim : 1. An improved process of preparation of thymol which comprises reacting cyclic terpene ketones of the kind as herein described , over a novel catalyst comprising metals from group VIII and group IB in a solid support such as herein described, in presence of a solvent or a diluent, at a tenperature in the range of 120 to 600° C, under hydrogen atmosphere at a pH in the range of 4 to 12, for a period in the range of 24 to 360 hr, recovering and purifying the product by conventicMial methods, the process is characterized in using the novel catalyst as definedabove. 2. An improved process as claimed in claims 1 wherein the solvent or dilutents used is selected from nitrogen, oxygen, hydrogen, helium or liquids such as pyridine, decane, dodecane, hexadecane etc. and substrates itself 3. An improved process as claimed in claims 1 to 2, wherein the cyclic terpene ketones used is such as menthone, isomenthone, mixture of manthone-isomenthone, piperitone and pulegone etc. and of essential oils containing these compounds. 4. An improved process as claimed in claims 1 to 3, wherein the product is obtained by filtering out the catalyst and the crude product fractionated and crystallized to get the desired product. 5. An improved process of preparation of thymol substantially as herein described with reference to examples.

Documents:

637-del-1999-abstract.pdf

637-del-1999-claims.pdf

637-del-1999-complete specification(granted).pdf

637-del-1999-correspondence-others.pdf

637-del-1999-correspondence-po.pdf

637-del-1999-description (complete).pdf

637-del-1999-form-1.pdf

637-del-1999-form-2.pdf

637-del-1999-form-4.pdf