Method for preparing odorant and fragrance on film evaporator

Abstract

The present invention relates to a process for preparing odorants or fragrances by carrying out a thermal rearrangement reaction of compounds in a film evaporator under distillation conditions under mild and resource-saving conditions, and also to the products, i.e. The compounds directly produced by the process. In particular, the present invention relates to an alternative new process for the preparation of 3-(4-isopropylcyclohexene-1-yl) propionaldehyde odorant via a thermal rearrangement reaction in a film evaporator.

Description

Technical Field

[0001] The present invention relates to a method for preparing flavors or fragrances by carrying out a thermal rearrangement reaction of compounds under distillation conditions in a thin film evaporator under mild and resource-saving conditions, and also to the products, i.e. the compounds directly produced by the method. In particular, the present invention relates to an alternative new method for preparing 3-(4-isopropylcyclohexen-1-yl)propanal of formula (I).

[0002] Background Art

[0003] The main requirements for the manufacturing process of chemical products are cost-effectiveness, high yield and selectivity, while complying with all regulations related to safety. A material-efficient and therefore cost-effective preparation would provide a significant competitive advantage over competitors, especially in view of the growing demand for certain chemical products (e.g. fragrances and flavors). In this context, it should be remembered that the efficient use of materials reduces production costs and at the same time can also increase the productivity of the manufacturing process.

[0004] Therefore, during the manufacture of chemical compounds and their further processing as raw materials, chemical products, components or the like, optimizing the use of materials in production while taking environmental aspects into account is a major challenge.

[0005] In this context, chemical manufacturing methods should also take into account so-called green chemistry aspects, i.e. environmental friendliness.

[0006] Another key aspect is therefore to make the manufacturing process as material-efficient as possible by using recycled residues, unconverted materials, waste or by-products as secondary raw materials for further processes or, ideally, as starting materials for the underlying process itself, thereby protecting the environment and reducing production and disposal costs at the same time. Reusing resources in this way saves existing stocks and thus makes a decisive contribution to the sustainability of the manufacturing process, while also reducing the costs incurred.

[0007] Furthermore, mild reaction conditions are preferred due to low energy input and generally result in more controllable and uniform product selectivity in chemical processes.

[0008] Temperature-sensitive substances, such as many aromas and / or flavorings, can only be heated to high temperatures for a short time in order to counteract unwanted thermal decomposition processes. Classical distillation processes often result in the components to be distilled being subjected to thermal stress for a long time. If the desired chemical product is thermolabile, this can have a negative impact on its yield as well as its quality. Therefore, rapid distillation methods with satisfactory separation properties and short residence times are required.

[0009] Fast reaction and thus short residence time can improve space-time yield and reduce thermal stress on chemical products, which usually has a negative impact on the quality and properties of the products. As already mentioned, the cause may be, for example, thermal decomposition due to excessive thermal stress.

[0010] Today, one way to distill large amounts of starting material in short residence times without exposing it to excessive thermal stress is to use thin-film evaporators, in which the material to be treated is applied as a thin film to the inner surface of the evaporator with only a very short contact time with the heated surface.

[0011] Thin-film evaporators are primarily suitable for the thermal separation of substance mixtures by distillation; thin-film evaporators are therefore used in particular for the purification of substance mixtures.

[0012] For example, EP 3103538 A1 describes a thin-film evaporator for thermally separating volatile fractions from heavier boiling residues in a substance mixture by evaporation, the thin-film evaporator having a closed, essentially cylindrical reactor vessel, the reactor wall of which can be heated by means of a heating device, an inlet for the feed to be separated, an outlet for the residue and an outlet for the vapor, and having at least one drive shaft assembly connected to a drive device, the drive shaft assembly having at least one scraping device with a rotor with scraper elements for the inner surface of the reactor wall.

[0013] For example, the cosmetics industry, the perfume industry and similar economic sectors have a growing demand for high-quality ingredients and active substances. Such substances can be, for example, aromatic substances and fragrances or odorous substances. Since fragrances usually have very specific odor characteristics, it is particularly desirable to synthesize such substances as pure as possible and without impurities, i.e., as selectively as possible, because impurities that may be present in the fragrances may destroy or adversely affect the characteristic odor impression and cause unpleasant secondary odors. Such impurities may also have a negative impact on the stability of the synthesized fragrances due to chemical interactions and cause unpleasant odors or change the basic odor impression. Therefore, it is necessary for such compounds to have the highest possible purity.

[0014] Although, as mentioned above, it is currently possible to remove unwanted by-products, reaction starters or degradation products from substance mixtures on a large scale by means of distillation, for example in thin-film evaporators, current production methods still involve high costs, low selectivity and low material efficiency.

[0015] Thermal rearrangement reaction usually forms the basis of many building-up processes, and usually only occurs under harsh thermal conditions. However, such high thermal stress usually leads to the thermal decomposition of the resulting compound or the corresponding by-product, which may produce unfavorable interactions with the product. As a result, the sufficient selectivity of the preparation and the good quality of the product can no longer be guaranteed. For example, as described in EP 2578671 A1, the synthesis of 3-(4-isopropylcyclohexene-1-yl) propanal is carried out via a heat-driven Claisen rearrangement. However, it can be observed that the selectivity of the reaction is low, because the by-product 5-isopropyl-2-methylene cyclohexanol is also formed in the acidic cleavage process of acetal.

[0016] For example, document EP 2247648 B1 describes a process for preparing lactam salts by reacting alkoxides with lactams by thin-film evaporation. In this process, the reaction of the alkoxide with the lactam takes place on a thin-film evaporator to form catalytically active lactam salts. The reaction releases the corresponding alcohol, which is then removed directly from the reaction mixture on the thin-film evaporator.

[0017] Patent document WO 2005030358 A1 discloses a thin film evaporator which is designed to improve separation efficiency and, if necessary, to carry out or accelerate chemical reactions during the evaporation process. For this purpose, in a preferred embodiment, the interior of the thin film evaporator is designed as a catalyst. Experiments have shown that a combination of distillation, absorption and chemical reactions can be carried out by installing a heterogeneous catalyst in the evaporation chamber and / or by installing a mass transfer surface and by adding the reactants directly to the evaporation chamber.

[0018] US Pat. No. 5,561,209 A discloses a continuous process for preparing polyorganosiloxanes by condensation of low molecular weight polyorganosiloxanols with one another or with oligomeric siloxanes in a thin film evaporator in the presence of a catalyst system.

[0019] A continuous process for preparing the aromatic citral is disclosed in WO 2008037693 A1. In particular, the document discusses the preparation of the corresponding acetal. The equipment described therein for preparing the unsaturated acetal preferably comprises a distillation column used as a reaction column, and the formed citral is continuously removed from the reaction mixture by distillation during the reaction.

[0020] An alternative continuous process for preparing citral by thermal cracking of 3-methyl-2-butene-1-aldehyde-diisoprene acetal is described in EP 0992477 B1. The thermal cracking of the acetal is carried out in the lower part or bottom of a distillation column having 5 to 100 theoretical separation plates.

[0021] However, none of the cited prior art documents describes the preparation of fragrances or odorants by thermal rearrangement reactions in a thin film evaporator under controlled and material-efficient conditions. The high efficiency of the processes described therein is due to the mild reaction conditions, which avoid thermal stress on the products and side reactions. Summary of the invention

[0022] The present invention is therefore based on the general object of providing a process which enables the efficient and gentle preparation of fragrances or odorants.

[0023] Another object of the present invention relates to a highly selective process for preparing 3-(4-isopropylcyclohexen-1-yl)propanal.

[0024] The present invention therefore relates to an efficient preparation process which is combined with an efficient purification of the prepared fragrance or odorant in a single combined process step.

[0025] From a further point of view, the present invention also relates to the material-efficient and cost-effective preparation of fragrances or odoriferous substances taking into account environmental aspects. SUMMARY OF THE INVENTION

[0027] The problem of the invention is solved by the subject matter of the independent claims. Preferred embodiments emerge from the wording of the dependent claims and from the following description and examples of embodiments.

[0028] In a first aspect, the present invention relates to a method for preparing a fragrance or odorant by performing a thermal rearrangement reaction, the method comprising the following steps:

[0029] a) providing at least one reaction starting material and / or other reagents in a thin film evaporator;

[0030] b) subjecting the reaction starting materials from step a) to at least one thermal rearrangement reaction under distillation conditions in the thin film evaporator;

[0031] c) obtaining the fragrance or odorant.

[0032] In a further preferred variant of the aforementioned process, the product of step c) is the compound 3-(4-isopropylcyclohexen-1-yl)propanal. Therefore, a preferred further development of the present invention relates to a process for preparing the odorant 3-(4-isopropylcyclohexen-1-yl)propanal by thermal rearrangement reaction under distillation conditions in a thin film evaporator.

[0033] Surprisingly, in the case of the present invention, it is found that when a thermal rearrangement reaction is carried out in a thin film evaporator, the selectivity of the thermal rearrangement reaction can be improved, which in turn leads to a higher yield and increased purity of the chemical product, because the reaction conditions are milder. It is known that at higher temperatures, i.e., at higher thermal energy, the selectivity of the chemical reaction decreases. On the contrary, this means that at low temperatures, i.e., at lower thermal energy, the selectivity increases, and at high temperatures, it is foreseeable that almost uniform product distribution. However, it should be noted that at lower temperatures, chemical reactions may also be carried out more slowly generally, which may result in longer preparation times. It has been shown that the method according to the present invention represents an optimized balance between mild reaction conditions and the effective conversion of the reaction initiator, and therefore provides the best compromise between yield, purity and productivity.

[0034] However, the mild conditions of the invention are not only related to the temperature itself, but also to the residence time of the reaction mixture on the heated inner surface of the evaporator. The process according to the invention makes it possible to significantly shorten the local residence time and thus reduce the risk of local thermal stress, in particular for already converted, i.e. rearranged reactants, and thus reduce thermal decomposition, i.e. thermal product destruction. The proposed process is therefore particularly suitable for use in conjunction with heat-sensitive / temperature-sensitive fragrances and odorants.

[0035] These and other aspects, features and advantages of the present invention will become apparent to those skilled in the art by studying the following detailed description and claims. Any feature of one aspect of the present invention may be used or replaced in another aspect of the present invention. The embodiments included in this application describe the present invention rather than limiting the present invention.

[0036] Numerical examples given in the format "from x to y" include the explicitly stated values. If multiple preferred numerical ranges are explicitly stated in this format, all ranges resulting from combinations of the different endpoints are also included in the invention.

[0037] Advantageous further embodiments and variants of the invention are given in the dependent claims. DETAILED DESCRIPTION OF THE INVENTION

[0039] The first object of the present invention relates to a method for preparing a fragrance or odorant by performing a thermal rearrangement reaction, the method comprising the following steps:

[0040] a) providing at least one reaction starting material and / or other reagents in a thin film evaporator;

[0041] b) subjecting the reaction starting materials from step a) to at least one thermal rearrangement reaction under distillation conditions in the thin film evaporator;

[0042] c) obtaining the fragrance or odorant.

[0043] In carrying out the thermal rearrangement reaction, at least one reaction starting material is provided in a first step a).

[0044] Depending on whether the thermal rearrangement reaction takes place in the presence of further reagents (eg catalysts), further corresponding reagents are also provided in step a) of the process according to the invention.

[0045] A preferred embodiment of the present invention relates to thermal rearrangement reactions which require acidic conditions and / or occur under acid catalysis. In said case, step a) of the present invention comprises providing at least one reaction starter and / or at least one acid in a thin film evaporator.

[0046] Suitable acids in this case are, for example, organic acids and their acid salts, such as carboxylic acids, alcohols, phenols, enols, thiols, sulfates and sulfonic acids, phosphates and phosphonic acids, CH- and NH-acidic compounds and their salts. Also suitable are inorganic acids and their acid salts, such as hydrochloric acid, carbonic acid, phosphoric acid, nitric acid, nitrous acid, sulfuric acid, sulfurous acid, thiosulfuric acid and their salts. However, it is particularly preferred to use organic acids and their salts in step a).

[0047] In the process described herein, preference is given to using aliphatic carboxylic acids, substituted carboxylic acids, heterocyclic carboxylic acids and aromatic carboxylic acids and their salts (carboxylates). In the present case, compounds in which the OH group of the carboxyl group is replaced by another group (e.g. -OR, -NH2 or -Cl) (carboxylic acid derivatives), such as carboxylic esters, carboxylic acid amides and carboxylic acid halides and their salts, are also suitable acids.

[0048] They preferably have one or more carboxyl groups (-COOH). Suitable carboxylic acids include: acetic acid, acrylic acid, oxalic acid, formic acid, trifluoroacetic acid, succinic acid, fumaric acid, maleic acid, trichloroacetic acid, citric acid, aromatic carboxylic acids, such as acetylsalicylic acid, benzoic acid, phenylacetic acid and salicylic acid, amino acids, such as alanine, aspartic acid and glycine, and salts of the above acids.

[0049] In this case, particularly preferred acids are selected from the group consisting of organic acids and their acid salts, with particular preference given to carboxylic acids having one or more carboxyl groups and acid salts of the above compounds.

[0050] In another preferred embodiment of the present invention, salicylic acid is particularly preferably used and provided in step a).

[0051] The term "reaction starting materials" is understood to mean that the reactants used in the process according to the invention represent the starting materials for the thermally induced rearrangement reaction. However, these substances themselves may have been prepared from other starting materials in further preceding steps.

[0052] Step b) of the process described herein according to the invention comprises subjecting the reaction starting materials from step a) to at least one thermal rearrangement reaction in said thin-film evaporator under distillation conditions.

[0053] Thermal rearrangement reactions refer to all chemical reactions in which, with the breaking of intramolecular (i.e., internal) bonds and the formation of new bonds, structurally new compounds are formed by the displacement of individual atoms or groups of atoms. Thermal rearrangement is initiated with the aid of thermal energy, i.e., thermal energy in the form of heat must be supplied for thermal rearrangement reactions to occur.

[0054] Therefore, the reaction starting materials described herein are preferably compounds with interesting and surprising properties after undergoing a thermal rearrangement reaction. Such products may therefore preferably be aromatics or odorants and flavorings, such as the formula (I) compound 3-(4-isopropylcyclohexene-1-yl) propanal, which is used as a lily of the valley fragrance. Therefore, in a preferred embodiment, the present invention relates to a method for performing a thermal rearrangement reaction to alternatively prepare aromatics and flavorings (preferably aromatic 3-(4-isopropylcyclohexene-1-yl) propanal).

[0055] In principle, however, all compounds that are able to undergo thermal rearrangement reactions can be considered as reaction starting materials.

[0056] If the rearrangement involves a plurality of reaction starters or reagents, it is advantageous to feed them into the thin-film evaporator in a homogeneous manner.

[0057] In this case, ie in process step a), generally no conversion occurs, since the thermal activation energy required for the thermal rearrangement process must first be provided to the reaction starting material mixture. This preferably takes place only within the thin-film evaporator after feeding into the thin-film evaporator.

[0058] In the context of the present invention, a thin-film evaporator is understood to be a device for separating a reaction mixture by distillation, in which the reaction mixture to be separated is distributed uniformly and in a defined thin film on the heated inner surface of the evaporator by means of specially designed scrapers. Particularly preferred are vertically constructed thin-film evaporators, which are designed with internal means for distributing the reaction mixture and external means for heating the inner surface of the evaporator. The prepared reaction mixture containing the at least one reaction starter and / or further reagents is preferably fed into the upper part of the thin-film evaporator and then distributed as a thin film on the heated inner surface of the evaporator by means of a rotating scraper element.

[0059] Therefore, the thin-film evaporator used in the process according to the invention is preferably equipped with a rotating scraper system. The selection of a suitable scraper system depends on the properties of the reaction mixture, for example its viscosity.

[0060] The thin film evaporator used in this article has a cylindrical interior (whose evaporator inner surface can be heated to a defined temperature), a metering pump designed above the stirring blade for feeding the reaction mixture, a rotating scraper system with adjustable speed and a vacuum pump for regulating the pressure, a collecting glass flask at the lower end and a system for cooling and top removal of the vapor.

[0061] Therefore, in the present invention, the thermal rearrangement of the at least one reaction starting material and / or the further reagent takes place on the thin film evaporator, i.e. on the inner evaporator surface of the thin film evaporator. In such a reaction, reaction by-products and / or unreacted reaction starting materials are removed directly from the reaction mixture in the thin film evaporator by distillation.

[0062] Thus, the phrase "under distillation conditions" refers to the separation of certain reactants (reaction products or reaction starting materials) from a reaction mixture by thermal evaporation in the classical sense and subsequent reliquefaction. Thus, separation of substances by evaporation and subsequent condensation is a thermal separation process.

[0063] The reaction by-products and the reaction products enriched at the bottom of the collection flask are separated simultaneously, so that the reaction equilibrium is continuously shifted to the product side, which allows the reaction starting materials to be converted as completely as possible.

[0064] Such processes can therefore generally be classified as reactive distillations, since the reaction (in the present case thermal rearrangement) and the separation process (i.e. the distillative separation of the by-products formed during the rearrangement) are combined in one process step. Thus, the process according to the invention comprising reactive distillation is carried out on a thin-film evaporator.

[0065] The light fraction consisting of reaction byproducts and / or unreacted reaction starting materials is therefore distilled off at the top of the column and then condensed, while the product is enriched at the bottom in the collection flask. This leads in particular to a concentration of the product. The distilled compound can be further purified in an additional rectification step and can then be reused as a reaction starting material or reagent in other manufacturing processes.

[0066] In another preferred embodiment of the process according to the invention, the thermal rearrangement reaction is carried out under distillation conditions under additional inert conditions.

[0067] In an alternative embodiment thereof, an additional gas stripping process may be provided.

[0068] The use of a thin film evaporator as a reaction vessel for the preparation of fragrances or odorous substances provides the possibility of uniformly evaporating the reaction mixture contained therein in the form of a thin film. Since the thin film evaporator in the present invention is preferably operated in a vacuum, the process described herein enables the use of relatively low temperatures and is therefore suitable for mild thermal rearrangement and simultaneous separation of by-products, and thus enables the conversion of the starting material and the separation and purification of the product to be combined simultaneously in a single process step.

[0069] In addition, the continuously rotating scraper blades of the thin film evaporator ensure that the reaction starters are evenly distributed, so that the reaction equilibrium is already completely established when they flow through the interior of the thin film evaporator. In addition, a shorter residence time of the reactants at the heating surface is achieved, and at the same time a high evaporation rate is achieved, which makes the method described herein particularly suitable for the conversion of temperature-sensitive reactants. These reduced thermal stresses on the reaction starters used and on the reaction products, which are caused in particular by the shortened residence time compared to conventional flask experiments and the avoidance of local overheating of the reactants, make the method according to the invention characterized as a very gentle method, which reduces undesirable thermal decomposition.

[0070] Good mixing combined with low film thickness leads to maximum evaporation rates and shortest residence times in the evaporator at moderate temperatures, which enables quantitative and high-quality production of (temperature-sensitive) fragrances and odorants.

[0071] The operating settings of the thin-film evaporator, in particular the choice of temperature, pressure, liquid flow rate of the reaction mixture and the scraping speed (i.e. the rotational speed of the scraper system), depend largely on the type of thermal rearrangement reaction and the reaction starting materials used and are adjusted accordingly in order to minimize the typical residence time of the chemical components on the evaporation surface (i.e. on the heated surface) and to ensure gentle conversion and separation.

[0072] In the present invention, mild conversion or separation therefore means that the thermal stress and residence time during the rearrangement and / or distillation are low and the corresponding reaction products do not suffer any negative thermal damage, which may be significant in terms of thermal decomposition or changes in product properties (e.g. color, odor, stability, etc.).

[0073] The rapid reaction caused and the relevant short residence time make it possible to improve the space-time yield, and reduce the thermal stress to the reactant simultaneously. The reaction product formed by rapid separation from the reaction mixture makes it possible to achieve higher yield. In addition, compared with the multi-stage method, the method described herein is characterized in that its complexity is low. Therefore, the method described herein is characterized in that it is technically and economically advantageous method, which is particularly suitable as a large-scale method due to the simplicity of high space-time yield and implementation.

[0074] Another advantage of the method described in this article is that the thermal rearrangement reaction, which requires high temperatures to activate the rearrangement process, can be achieved by applying a vacuum to the thin film evaporator using moderate temperatures (by applying a corresponding vacuum to the thin film evaporator), which has a positive impact on energy costs and reduces thermal decomposition.

[0075] Overall, it has therefore been surprisingly found that when the thermal rearrangement reaction is carried out in a thin-film evaporator according to the process of the invention, the selectivity of the thermal rearrangement reaction is increased and higher yields and increased purity of the chemical products can be achieved.

[0076] It should also be emphasized that the equipment requirements associated with the described process are low. In particular, with regard to the thin-film evaporator, it serves both as a reactor for carrying out the thermal rearrangement and simultaneously as a distillation apparatus and thus becomes, on the one hand, a dedicated apparatus for carrying out the thermal rearrangement reaction and, on the other hand, optionally a separate distillation apparatus for purification.

[0077] This eliminates the need for laborious conversion and transfer of reaction products (which can result in yield loss). Time considerations must also be taken into account here. The savings in time and equipment are therefore reflected in the reduction of production costs. The method of the present invention is therefore very suitable for large-scale preparation of chemical products via thermal rearrangement.

[0078] The reactive distillation is preferably carried out at an operating temperature of the thin-film evaporator of preferably 160 to 260° C., preferably 180 to 240° C. and more preferably at an operating temperature of 230° C. This corresponds to a reaction temperature of approximately 220° C. in the thin-film evaporator.

[0079] On the other hand, the actual contact temperature of the reactants is preferably 160 to 240° C., even more preferably 180 to 220° C. The reaction temperature or contact temperature is particularly preferably 220° C.

[0080] Preferably, the residence time of the reactants on the inner surface of the thin-film evaporator is only a few seconds, which is significantly shorter than the residence time in reactive distillation.

[0081] The pressure in the evaporator is preferably from 500 to 1000 mbar, particularly preferably about 200 mbar, the pressure to be used depending on the product to be prepared.

[0082] The reaction product of the thermal rearrangement reaction in step c) of the process described herein is preferably obtained at the lower end of the thin-film evaporator in a collecting flask. Due to the high selectivity of the process described herein, the enriched product is obtained there in high yield and high purity.

[0083] The compound 3-(4-isopropylcyclohexen-1-yl)propanal is mainly used as a fragrance with lily-of-the-valley notes. Despite the large number of existing fragrances, there is still a general demand for new fragrances in the fragrance industry, which are an indispensable component in the fragrance industry and in the manufacture of cosmetics, personal care products, detergents and cleaning agents, etc. In addition to the search for new fragrances, in order to meet the high demand and be able to provide high-quality products and ingredients, the optimization of manufacturing methods in terms of efficiency, resource conservation and the environment is also a major challenge at present.

[0084] The currently used preparation methods of the aromatic 3-(4-isopropylcyclohexen-1-yl)propanal involve thermal rearrangement of the corresponding acetal with cleavage of the vinyl ether to give the desired product. However, the common production methods show low selectivity and therefore only provide low yields and low purities. In addition, the above-mentioned methods are not suitable for material-efficient and cost-reduced preparation.

[0085] In a preferred embodiment of the present invention, the process described herein relates to an optimized alternative process for the preparation of 3-(4-isopropylcyclohexen-1-yl)propanal.

[0086] Furthermore, preference is given to using the process according to the invention as an alternative preparation process for providing the popular aroma and flavoring agent 3,7-dimethylocta-2,6-dienal (also known as citral).

[0087] For the purposes of this document, a fragrance or odorant is any substance that can be used to create an olfactory impression, i.e. to convey an olfactory impression, or to change (modify or enhance) the olfactory perception of another substance. In order for such a substance to be useful for perfumery purposes, it should preferably not have any undesirable side effects, such as effects that are harmful to health or the environment, or effects that adversely affect the intended use of the product containing such odorant or fragrance.

[0088] As already mentioned at the outset, fragrances generally have a very specific odor profile. It is therefore particularly desirable to synthesize such products with a high degree of purity, i.e. without impurities and as selectively as possible, since even small amounts of impurities can destroy or adversely affect the characteristic odor impression and lead to unpleasant secondary odors. Such impurities can also have a negative impact on the stability of the prepared fragrance due to chemical interactions and can lead to unpleasant odors or change the basic odor impression. Therefore, it is desirable for such compounds to have the highest possible purity.

[0089] Current manufacturing methods often produce fragrances of insufficient purity and therefore need further optimization. In addition, due to the high demand for fragrances and odorants, more time-, material- and therefore cost-effective methods are needed to replace the current complex, expensive and therefore uneconomical production methods.

[0090] Although it is currently possible to remove unwanted by-products, reaction starters or degradation products from fragrances and odorants on a large scale by means of distillation, for example in thin-film evaporators, as described above, current production methods still involve high costs, low selectivity and low material efficiency.

[0091] Surprisingly, it has been shown that the method according to the invention is suitable for the selective and thus highly pure synthesis of odorants or fragrances. The synthesized fragrances or odoriferous substances thus have a stable odor profile without any secondary odors and are therefore suitable for further processing into perfumed products or perfume oils.

[0092] The process according to the invention is therefore particularly suitable for the economical preparation of highly concentrated and pure fragrances and odorants in high yields by combining a gentle and selective synthesis with reduced thermal stress and simultaneous distillation and thus purification of the product.

[0093] Another preferred development of the invention relates to the process according to the first subject matter of the invention, wherein the at least one thermal rearrangement reaction comprises at least one pericyclic reaction.

[0094] In this context, pericyclic reactions are rearrangement reactions that undergo cyclic transition states by concerted (i.e., simultaneous) intramolecular transfer of electrons without the presence of free radicals or ionic intermediates. Examples of such reactions include sigmatropic rearrangements, in particular sigmatropic rearrangements of the Claisen or Cope type, cycloadditions, chelation reactions or electrocyclization reactions. In principle, pericyclic rearrangement reactions can be initiated thermally or photochemically, with thermally driven rearrangement reactions being preferred in the present invention.

[0095] It has been shown that, using the process according to the invention, such rearrangements can be carried out particularly selectively, which is reflected in high yields and high purity of the products. The process according to the invention is therefore particularly suitable for carrying out pericyclic rearrangements in connection with the preparation of odorants or fragrances.

[0096] As explained above in connection with the first subject matter of the invention, the selectivity of the thermal rearrangement reaction is caused in particular by the mild process conditions.

[0097] An alternative variant of the first subject matter of the invention relates to a method for carrying out at least one rearrangement of the Claisen rearrangement, Cope rearrangement and / or intramolecular Prins reaction type.

[0098] Of the sigmatropic rearrangement reactions, the Claisen rearrangement and the Cope rearrangement are of particular interest. These reactions are used alone or in combination to synthesize well-known fragrance compounds such as citral, mixtures of the cis- and trans-isomers of geranial and neral.

[0099] In the known synthesis of fragrances, according to Claisen and Cope, the corresponding acetal is first cleaved and then rearranged. EP 0992477 B1 describes a continuous distillation process for the synthesis of citral. According to WO 2008037693 A1, the synthesis is carried out in a distillation column used as a reaction column, wherein the vapor is returned to the column in gaseous form.

[0100] Surprisingly, it has been shown that such reactions and syntheses can be carried out effectively in a thin film evaporator. The reaction starting materials are not converted at the bottom of the column, but in a fine film along the inner surface of the thin film evaporator. In contrast to the flask experiments described above, the constant circulation of the reaction mixture by the scraper system prevents local overheating and reduces the thermal stress on the reactants as much as possible.

[0101] Acid-catalyzed carbonyl-ene reactions, also called Prins reactions, belong to the class of cycloadditions. Intramolecular Prins reactions, i.e. intramolecular carbonyl-ene reactions, are used, for example, in the synthesis of the aromatic isopulegol from citronellal.

[0102] Surprisingly, it has been found that the odorant isopulegol can also be prepared in high yield and high purity by means of the process described here which is based on a thermal rearrangement reaction in a thin-film evaporator under distillation conditions.

[0103] It can be seen that the preparation of a large number of odorants or fragrances can be traced back to Claisen, Cope and Prins type pericyclic rearrangement reactions.

[0104] Surprisingly, it has been shown that according to the process of the invention, these rearrangements, alone or in combination, are particularly selective. The products obtained have high yields and high purity. The process of the invention is therefore particularly suitable for carrying out at least one rearrangement according to Claisen, according to Cope and / or Prins, alone or in combination, in particular for the preparation of odorants or fragrances.

[0105] In a preferred embodiment of the present invention, the process according to the invention for carrying out a thermal rearrangement reaction involves carrying out a rearrangement according to Claisen.

[0106] In a preferred embodiment of the present invention, the process according to the invention for carrying out a thermal rearrangement reaction involves carrying out a rearrangement according to Cope.

[0107] Sigmatropic rearrangements are a special form of pericyclic reactions and are characterized by the displacement of σ bonds. The number of σ and π bonds remains constant before and after the rearrangement.

[0108] The oxy-Cope rearrangement requires a lower activation energy than the Cope rearrangement and therefore occurs at a lower temperature. Thus, this Claisen reaction (oxy-Cope rearrangement), similar to the well-known Cope rearrangement, is a [3,3]-sigmatropic rearrangement in which a carbon atom is replaced by an oxygen atom.

[0109] A rearrangement reaction that occurs sequentially, a so-called cascade reaction, is an intramolecular sequence of rearrangements that occurs spontaneously or intentionally sequentially. In general, a sigmatropic rearrangement preferably occurs sequentially under constant reaction conditions and is therefore particularly suitable for carrying out the process according to the invention in a thin-film evaporator.

[0110] As shown in Examples 2 and 7 (citral), the methods described herein are suitable for performing both single and sequential multiple [3,3]-sigmatropic rearrangements.

[0111] Tandem rearrangements are particularly preferred, in the order of Claisen-Cope.

[0112] Therefore, in a next further development of the first subject-matter of the present invention, the invention relates to a method in which at least one [3,3]-sigmatropic rearrangement is carried out.

[0113] Surprisingly, it has been shown that according to the process of the invention these [3,3]-sigmatropic rearrangements occur particularly selectively, either individually or in combination. The resulting products can be isolated in high yields and high purity.

[0114] In a further preferred embodiment of the present invention, the process according to the invention for carrying out a thermal rearrangement reaction therefore involves carrying out a coupled Claisen and Cope rearrangement in all possible combinations.

[0115] Therefore, in a preferred embodiment, the present invention describes a technical optimization of the Claisen rearrangement according to the invention, which is based on an improved distillation process under reduced thermal stress. Formally speaking, this improvement in terms of equipment and therefore in terms of process technology enables solvent-free implementation in two chemical reaction steps under reactive distillation conditions, in a short time and at low cost, on the one hand, thermal rearrangement, and on the other hand, purification by distillation.

[0116] Another preferred variant of the first aspect describes the method according to the invention, which further comprises providing at least one acid as reagent in step a).

[0117] The acids used are particularly preferably selected from the group consisting of organic acids and preferably aliphatic carboxylic acids, substituted carboxylic acids, heterocyclic carboxylic acids and aromatic carboxylic acids and their acid salts, with particular preference given to aromatic carboxylic acids and in particular salicylic acid.

[0118] Many rearrangement reactions can be accelerated or made more selective by using such catalysts.

[0119] However, the conversion of the reaction starting materials to the reaction products can in principle also be carried out without a catalyst, i.e. only by heating. However, the presence of an acid catalyst as described herein is particularly preferred and advantageous. The above-mentioned acids and their acid salts are therefore particularly suitable as acid catalysts, wherein organic acids and their salts are preferably used.

[0120] Preferably, the acid is added as a reagent to the reaction starting materials, and then the homogeneous reaction mixture is fed from a storage container via a metering pump above the stirring blade of the thin film evaporator.

[0121] Thermal rearrangement reactions, such as the Claisen-type rearrangement, generally only occur at very high temperatures. By using acidic catalysis, these reactions can be carried out at correspondingly milder temperatures, but strong acids, such as phosphoric acid or Lewis acids, are generally used for this purpose.

[0122] The preferred acids described herein are characterized by their good solubility in organic systems and their low tendency to form corrosion and are therefore particularly suitable for use in the milder process of the present invention in a thin film evaporator.

[0123] It has been shown that the already mild process conditions can be further mitigated, which results in a more gentle handling of the reactants, and in particular the reaction products. This means that the rearrangements described herein to produce the desired reaction products can be carried out economically and efficiently, without requiring large amounts of energy input, and with high selectivity.

[0124] Particularly preferably, salicylic acid is provided as reagent in step a) of the process according to the invention for the thermal rearrangement reaction in a thin-film evaporator under distillation conditions.

[0125] It was also observed that the selectivity of the rearrangement, and in particular the selectivity of the Claisen rearrangement, was increased by using an acid selected from organic acids and preferably aliphatic carboxylic acids, substituted carboxylic acids, heterocyclic carboxylic acids and aromatic carboxylic acids and their acid salts, and thus almost no by-products were generated when the rearrangement was carried out. As a result, it was found that the chemical conditions for carrying out the Claisen rearrangement were significantly improved, and the selectivity of the rearrangement was observed to increase from about 70% to more than 96%.

[0126] This increase in selectivity makes a further decisive contribution to increasing the efficiency of the production method.

[0127] Thus, particularly selective and therefore efficient conversions can be observed with respect to the Claisen rearrangement. The particularly mild reaction conditions and the use of acids as described herein lead to very pure products in high yields.

[0128] A preferred embodiment of the present invention relates to carrying out a thermal rearrangement reaction comprising at least one Claisen-type rearrangement, wherein said reaction is carried out using salicylic acid.

[0129] The method according to the first aspect and the preceding embodiments or variants, further comprising providing salicylic acid as a reagent for the Claisen-type thermal rearrangement in step a), thus represents another preferred embodiment of the present invention.

[0130] The amount of acid used must be determined according to the product to be prepared. However, it is preferred to use only catalytic amounts. These amounts vary, for example, between 1 mol% and 10%, and are preferably about 5 mol%.

[0131] In the next variant of the above process, the product of step c) is a compound of formula (I) 3-(4-isopropylcyclohexen-1-yl)propanal:

[0132]

[0133] Also particularly preferred are the stereoisomers, in particular the enantiomers and diastereomers, of the compounds of formula (I), either individually or in mixtures.

[0134] As will be explained in more detail below, the compounds of formula (I) can be synthesized by a process as described herein comprising at least steps a), b) and c). For this purpose, the corresponding acetals are assumed to be reaction starting materials, which are provided by the acid-catalyzed addition of the appropriate allyl alcohols onto allyl vinyl ethers.

[0135] The synthesis of the compound of formula (I) 3-(4-isopropylcyclohexen-1-yl)propanal has been described in EP 2578671A1 and comprises the following steps:

[0136] i) The corresponding acetal of formula (II) is prepared by reacting the corresponding allyl alcohol with the corresponding alkyl vinyl ether in the presence of a protic acid, such as phosphoric acid.

[0137] ii) By reacting the acetal with a catalytic amount of an acid (eg hexanoic acid) in a high boiling point solvent, the desired aldehyde of formula (I) is obtained via a vinyl ether as an intermediate.

[0138] However, the low selectivity of the described Claisen rearrangement is problematic, since during the acidic cleavage of the acetal (II) 5-isopropyl-2-methylene-cyclohexanol (III) is also formed.

[0139] This is illustrated in the following reaction scheme:

[0140]

[0141] The use of salicylic acid as a catalyst for the Claisen rearrangement of the present invention leads to significantly higher reaction selectivity, thereby suppressing the formation of 5-isopropyl-2-methylenecyclohexanol (III) to a great extent during the acidic cleavage process of acetal (II), and the obtained product has a high yield and high purity, thereby improving the economic benefits of the preparation.

[0142] The odorants of the known formula (I) compound 3-(4-isopropylcyclohexene-1-yl) propanal have thermal instability. As described herein, the short residence time and the associated reduced thermal stress make it possible to offset the effects of the thermal decomposition process and ensure high product quality. This avoids the production of unwanted thermal decomposition products, which may interact adversely with the product or cause unpleasant secondary odors, or may destroy or adversely affect the characteristic odor impression, or have an adverse effect on the stability of the fragrance.

[0143] The process according to the invention therefore allows the synthesis of products which are as pure and free of impurities as possible, ie as selective as possible, and is therefore particularly suitable for the preparation of high-quality and stable fragrances or odorants.

[0144] Example 8 of the publication EP 2578671A1, which relates to the synthesis of 3-[(4R)-4-isopropylcyclohexen-1-yl]propanal, shows that the process described therein provides the desired product in a purity of only 52%. This corresponds to a theoretically possible yield of 58%. Only further purification was achieved with a purity of 96.5%. Therefore, after the second purification, a significantly lower yield of about 30% can be expected. It should also be noted that the caproic acid used therein is classified as a toxic substance.

[0145] As can be seen from inventive example 2, a significantly purer product with a purity of 72% was obtained immediately after synthesis. Subsequent purification ultimately yielded an even purer product with a purity of 98.2%.

[0146] It can thus be observed that the process according to the invention provides significantly purer products on a larger scale than conventional production processes. In addition, the toxic chemicals used are replaced by significantly less dangerous substances.

[0147] A direct comparison of the distillation processes shows that the process according to the invention operates under significantly milder conditions (comparison of Examples 2 and 3) and, moreover, avoids the use of environmentally harmful, air- and light-sensitive substances such as trioctylamine and dibenzyl ether.

[0148] The methods described herein operate according to the following reaction schemes (Path A and / or Path B):

[0149]

[0150] The product obtained by the reaction according to "path A" is equivalent to the recovery of the starting material, which can be reacted again. Based on the method of the present invention, the by-products that may be produced can therefore be effectively reused, and thus high yield, high purity, high selectivity and a small amount of unwanted by-products can be achieved.

[0151] Based on the mild conversion brought about by low thermal stress, selectivity and purity can be maximized without sacrificing yield.

[0152] Furthermore, it can be stated that the mild reaction conditions of the process according to the invention are preferred due to the low energy input and lead to a controllable and uniform selectivity. Short residence times and the use of acid catalysts make it possible to increase the space-time yield and reduce the thermal stress on the chemical products, which usually has a negative impact on the quality of the products, for example due to thermal decomposition.

[0153] Furthermore, it can be shown that, compared with Example 3, significantly fewer reactants are involved in the process, the demand for chemicals is lower, and therefore significant savings in time, costs and resources can be achieved with the process according to the invention.

[0154] Thus, it can be shown that the process of the present invention is significantly better in terms of material efficiency than conventional manufacturing processes as well as other distillation processes (eg, reactive distillation), as shown in the examples described herein.

[0155] In another embodiment of the process according to the invention, the reaction starting material is selected from acetals of formula (IIa), (IIb) and / or (IIc):

[0156]

[0157] The group R in the compound of formula (IIa) represents a straight chain or branched C 1-20 An alkyl group, a benzyl group, an acetyl group, a phenyl group, -CH2-CH2-OCH3, -CH(CH3)-CH2-OCH3, -(CH2)2-O-(CH2)2-O-CH=CH2, -(CH2)2-O-(CH2)2-O-(CH2)2-O-CH=CH2 or 2-methylene-tetrahydrofuran, and R in the compound of formula (IIc) represents a linear or branched C 1-20 Alkyl groups, -(CH2)2-O-(CH2)2- or -(CH2)2-O-(CH2)2-O-(CH2)2-, and their stereoisomers, in particular diastereomers and enantiomers, and mixtures thereof

[0158] The compounds of formula (IIa), (IIb) or (IIc) may exist in various forms corresponding to the possible structural isomers (regional isomers) of the group R, as well as stereoisomers of formula (IIa), (IIb) or (IIc), in particular enantiomers, diastereomers, and mixtures of stereoisomers in any mixing ratio.

[0159] Surprisingly, it has been shown that the use of a thin-film evaporator as reactor enables the preparation of 3-(4-isopropylcyclohexen-1-yl)propanal (I) starting from acetals of the form (IIa), (IIb) or (IIc).

[0160] By functionalizing the side chains with the preferred residues described herein, further increases in selectivity were observed in the rearrangement of acetals to the desired products.

[0161] In the Claisen rearrangement, a particularly strong increase in the selectivity is observed in connection with the acid catalysis described herein.

[0162] With regard to the ethyl group, the butyl group and -(CH2)2-O-(CH2)2-O-CH=CH2 as radical R, a particularly marked increase in the selectivity and thus also a higher purity and yield is observed.

[0163] Therefore, an alternative further development of the process according to the invention relates to reaction starting materials of the formula (IIa), wherein the radical R of the acetal of the formula (IIa) is preferably an ethyl radical, a butyl radical and -(CH2)2-O-(CH2)2-O-CH=CH2.

[0164] In a preferred embodiment, the radical R of the acetal of the formula (IIa) is particularly preferably -(CH2)2-O-(CH2)2-O-CH=CH2.

[0165] The above-described embodiment shows the greatest selectivity-increasing effect and is therefore particularly preferred in the case of the present invention.

[0166] In a next embodiment, the invention relates to a process which further comprises an additional / preceding process step 0) before step a), wherein in step 0), the reaction starting materials of the formula (IIa), (IIb) and / or (IIc) are provided via acid-catalyzed addition of 5-isopropyl-2-methylenecyclohexanol (formula (III)) to the corresponding vinyl ether of the formula (IV):

[0167]

[0168] Wherein the group R represents a straight chain or branched C 1-20 An alkyl group, a benzyl group, an acetyl group, a phenyl group, -CH2-CH2-OCH3, -CH(CH3)-CH2-OCH3, (CH2)2-O-(CH2)2-O-CH=CH2, (CH2)2-O-(CH2)2-O-(CH2)2-O-CH=CH2 or 2-methylenetetrahydrofuran.

[0169] Step 0) of the process according to the invention therefore relates to the preparation of the reaction starting material according to the invention, ie the corresponding acetal of formula (II) as described herein, by acidic reaction of the known compound 5-isopropyl-2-methylenecyclohexanol of formula (III) with a vinyl ether of formula (IV).

[0170] The resulting acetal (II) is cleaved using acid catalysis to the corresponding vinyl ether, which is directly converted thermally to the desired aldehyde 3-(4-isopropylcyclohexen-1-yl)propanal of the formula (I) by Claisen rearrangement.

[0171] As described herein, the conversion of the acetals of the formula (IIa), (IIb) and (IIc) described herein into 3-(4-isopropylcyclohexen-1-yl)propanal of the formula (I) according to the process of the invention is significantly more selective than the processes of the prior art, wherein significantly higher yields and purer products can be obtained. However, according to reaction scheme 1, certain small proportions of by-products may be obtained, for example 5-isopropyl-2-methylene-cyclohexanol of the formula (III) described herein. The combination of the process for thermal conversion described herein with simultaneous purification of the reactants by distillation makes it possible to collect such by-products in essentially pure form as a result of the distillation process and then reuse them in step (0) for the preparation of the reaction starting materials of the mentioned formula (IIa), (IIb) and (IIc), thus ensuring a material-efficient use of the raw materials used.

[0172] This therefore emphasizes the environmentally friendly, resource-saving and cost-saving properties of the process according to the invention.

[0173] According to another further development of the process according to the invention, preferably a Lewis acid or (Brønsted) acids are used in step 0) as acid catalysts for the acid-catalyzed addition.

[0174] Preferably, the Lewis acid and Acids are used as the acid for the acid-catalyzed addition. In particular, magnesium salts such as magnesium (II) chloride, magnesium (II) sulfate, ammonium sulfate, phosphoric acid and zeolite are preferred.

[0175] The acids used here as catalysts lead to an increase in the selectivity of the addition reaction.

[0176] In a further variant of the invention and therefore in a further variant of the process according to the invention, for the acid-catalyzed addition of 5-isopropyl-2-methylenecyclohexanol (formula (III)) to the corresponding vinyl ether of formula (IV) in step 0) of the process according to the invention, the corresponding vinyl ether of formula (IV) is used in a 1.1- to 5.0-fold molar excess.

[0177] The use of the vinyl ether of the formula (IV) in a defined molar excess thus influences the selectivity for the formation of the acetals, ie the reaction starting materials of the formulae (IIa) and (IIc).

[0178] In particular, it is preferred to use the vinyl ether of formula (IV) in a 1.2 to 2.0-fold molar excess.

[0179] When the vinyl ether of formula (IV) is used in such an excess amount, the maximum selectivity-enhancing effect of the addition reaction described herein on the reaction starting material can be observed.

[0180] In this case, particular preference is given to recovering the vinyl ether of the formula (IV) remaining in the reaction mixture by distillation.

[0181] Unreacted or excess vinyl ether of the formula (IV) from step 0) of the process according to the invention is preferably recovered by distillation. Vacuum distillation is particularly preferred.

[0182] Vacuum distillation requires lower temperatures and is therefore used as a particularly gentle process using moderate temperatures.

[0183] The distillative reprocessing of the vinyl ether of the formula (IV) from step 0) enables the vinyl ether to be used again in a subsequent acid-catalyzed reaction with 5-isopropyl-2-methylene-cyclohexanol of the formula (III) for the preparation of further reaction starting materials of the formulae (IIa), (IIb) and (IIc) or for other purposes.

[0184] This material-efficient use of raw materials makes a decisive contribution to the economic viability of the process described herein. This reuse preserves existing resources and makes a decisive contribution to a sustainable and environmentally friendly process, while minimizing production and disposal costs.

[0185] In a particularly preferred further development of the method described in this article, the method is operated as a continuous process.

[0186] Continuous processes are particularly useful for processing large quantities of raw materials and are characterized by a continuous, ie uninterrupted, process. Continuous processes make it possible to reduce the number of intermediate steps, such as refilling or cooling and heating equipment, and are therefore more economical than batch processes.

[0187] Furthermore, the continuous manufacturing process ensures a constant, i.e. consistent, product quality without quality fluctuations between individual batches.

[0188] In a continuous process, a constant flow balance is established. Through the continuous separation of the product, the reaction equilibrium is shifted towards a higher yield. In addition, due to the distillation characteristics of the present invention, the continuous separation of unreacted starting materials or by-products makes it possible to achieve a higher purity of the product, because the possibility of possible side reactions is thus significantly reduced.

[0189] In general, continuous processes have significant economic advantages over batch processes and are particularly suitable for industrial-scale manufacturing methods, and are therefore particularly preferred in the context of the present invention.

[0190] In order to carry out the thermal rearrangement reaction in a continuous or semi-continuous process, the thin film evaporator described herein can be expanded into a circulation reactor. For this purpose, the reaction starting materials are pumped back into a storage container and fed back into the upper part of the stirring blade of the thin film evaporator via a metering pump. This leads to a prolonged reaction time and a shortened residence time, so that the complete conversion of the reaction starting materials can be ensured.

[0191] In particular, it is preferred to subject the distilled material to a distillation separation process again before returning it to the system. For this purpose, it is recommended to use a device suitable for fractional distillation and only return the corresponding reaction starting material to the thin film evaporator.

[0192] In this way, unreacted reaction starting materials can be returned to the manufacturing process to reduce the amount of environmentally harmful reaction by-products and at the same time ensure that the raw materials are used in a materially and cost-effective manner.

[0193] It should also be emphasized that continuous processes are generally more stable and uniform due to constant reaction conditions and thus ensure higher selectivity of the reaction, which can improve product purity and yield.

[0194] Furthermore, a preferred further development of the invention describes a process which comprises recycling 5-isopropyl-2-methylenecyclohexanol of the formula (III), further starting compounds of the process and / or unrearranged reaction starters.

[0195] In the reactive distillation process according to the invention, in which the product is concentrated in the receiving flask, unreacted reaction starters or precursors and by-products can be removed by distillation and then returned to the process.

[0196] In particular, the compound 5-isopropyl-2-methylenecyclohexanol of formula (III) is preferably recovered. Although the selectivity of the reaction described herein is increased, this compound may still be produced as a possible by-product, which can then be used again in step 0) of the process to prepare the reaction starting material.

[0197] This saves resources and at the same time saves the cost of disposal and repurchasing the same compound.

[0198] The preferred recycled raw materials described herein enable optimized and efficient use of materials in production, both for environmental reasons and to enable reduction of incurred manufacturing costs.

[0199] Finally, in a second aspect, the present invention relates to a product directly prepared by a process according to the invention as described herein.

[0200] As explained above, the methods described herein provide products with excellent purity in high yields based on an optimized and highly selective manufacturing process under distillation conditions. At the same time, the products described herein can be prepared on a large scale in a cost-effective and environmentally friendly manner.

[0201] The high efficiency of the process and the resulting products makes it possible to fully meet the high demand in an economically efficient manner.

[0202] In a preferred embodiment, the product is prepared directly by the process according to the invention, such as the compound of formula (I) 3-(4-isopropylcyclohexen-1-yl)propanal, which is preferred herein, and is particularly useful as a fragrance with a lily of the valley scent. DETAILED DESCRIPTION

[0203] Example

[0204] The present invention is described in more detail below with reference to exemplary embodiments. First, the examples given relate to the preparation of compounds of formula (I) and particularly preferred compounds. In addition, it should also be noted that the IUPAC nomenclature may differ from the common names used so far.

[0205] For spectral data, the following English rule applies regarding the use of dots as separators for numerical data to ensure that measurements are clearer. In this case, in data of the form "δ = 7.12 (dd, J = 3.7, 0.9 Hz, 2H)", the measurements should be read as "δ = 7.12", "3.7", and "0.9". The alternative dot-comma rule is used for NMR data.

[0206] The synthesis of the compound of formula (I) 3-(4-isopropylcyclohexen-1-yl)propanal starting from the same starting material 4-isopropyl-1-methylene-2-[1-[2-(2-vinyloxyethoxy)ethoxy]ethoxy]cyclohexane from Example 1 is described in Examples 2 and 3 below.

[0207] Example 1: Acetal

[0208] Synthesis of 4-isopropyl-1-methylene-2-[1-[2-(2-vinyloxyethoxy)ethoxy]ethoxy]-cyclohexane (reaction starting material)

[0209]

[0210] In a 2L three-necked reaction flask with a dropping funnel, a powerful condenser and a magnetic stirrer, 500.00g (2.91mol, purity 89.8%) of 5-isopropyl-2-methylenecyclohexanol and 1.68g (0.01mol) of 85% phosphoric acid were placed and heated to 30°C. Then 923.18g (5.82mol) of diethylene glycol divinyl ether was added so that the temperature rise did not exceed 40°C. The reaction was stirred for another 4 hours at the same temperature until complete conversion, then cooled to room temperature. The reaction mixture was then dissolved in 1.3L tert-butyl methyl ether and stirred with 1.3L saturated sodium carbonate solution for 20 minutes. Phase separation was performed and the organic phase was washed with 1.0L saturated sodium carbonate solution. The aqueous phase was extracted once with 800mL tert-butyl methyl ether. The organic phases were combined and dried over sodium sulfate, then filtered. Finally, the volatile components, the solvent and the excess diethylene glycol divinyl ether were distilled off in vacuo (Sdp. 60° C. at p=2.5 mbar). 914.2 g of the residue obtained in this way were used directly in the subsequent reactions (Examples 2 and 3) as crude 4-isopropyl-1-methylene-2-[1-[2-(2-vinyloxyethoxy)ethoxy]ethoxy]cyclohexane.

[0211] Spectral data:

[0212] EI-MS m / z(%):268(1,[M-44] + ),225(2),180(4),162(19),137(65),115(58),110(54),93(50),87(100),81(85),68(85),55(19),43(77),29(15).

[0213] 1 H-NMR (400MHz, CDCl3, 300K): δ=7.18-7.15(m,1H),7.13(dd,J=4.8,1.9Hz,1H),7.07(d,J=1.7Hz,1H),7.07-7.03(m,1H),4.88(s,2H),1.68(s,6H)ppm.

[0214] 13C-NMR (101MHz, CDCl3, 300K): δ=206.99,192.78,191.80,191.67,163.50,133.88,132.25,132.13,131.98,130.04,129.15,128.86,1 28.60,128.56,127.95,127.26,126.32,125.51,124.50,123.52,86.16,82.02,70.23,64.25,63.17,63.15,30.92,29.47,29.12ppm.

[0215] Example 2: DV reaction

[0216] According to the method of the present invention, 3-(4-isopropylcyclohexen-1-yl)propanal of formula (I) is synthesized using a thin film evaporator

[0217]

[0218] The reaction mixture was fed from the storage container via a metering pump above the stirring blades of a thin-film evaporator equipped with cooling and top removal, adjustable setting of the rotor blades, a vacuum pump for setting the pressure and a collecting glass flask at the bottom.

[0219] In order to buffer the pH value, 170.00g of 5% sodium carbonate aqueous solution was placed in the receiving flask. The rotating speed was set to a stirring speed of 500rpm, and a vacuum of 800 mbar was applied. The thin film evaporator was heated to T=230°C. In a storage container emptied by a metering pump, 160.00g of 4-isopropyl-1-methylene-2-[1-[2-(2-vinyloxyethoxy)ethoxy]ethoxy]cyclohexane and 8.00g (57.34mmol, 5.0m%) of salicylic acid from Example 1 were weighed and stirred. The solution was applied to the thin film evaporator at a rate of 2.5mL / min. During the reaction, light volatiles were distilled out at the top of the column. The product 3-(4-isopropylcyclohexene-1-yl) propanal of formula (I) was enriched at the bottom of the receiving flask. After the reaction was completed, the device was cooled and depressurized. 150mL tert-butyl methyl ether was added to the reaction solution in the receiving flask, and then extracted. After phase separation, the aqueous phase was extracted with 150mL tert-butyl methyl ether again, and then phase separation was performed. The combined organic phase was washed with 250mL saturated sodium chloride solution. After phase separation, the organic phase was dried over sodium sulfate and then filtered. The solvent was then removed in vacuo. 119.04g of crude product was obtained in this way, and the purity was 72%.

[0220] 119.4 g (72% purity) of crude 3-(4-isopropylcyclohexen-1-yl)propanal of the formula (I) were purified by distillation on a canned column. 77.4 g of 3-(4-isopropylcyclohexen-1-yl)propanal of the formula (I) were isolated with a purity of 98.2% (74-75° C., at 1.0 mbar; R (reflux) / D (removal)=100 / 1).

[0221] The analytical data correspond to those in the literature (EP 2578671 A1).

[0222] Example 3: Reactive distillation

[0223] Synthesis of 3-(4-isopropylcyclohexen-1-yl)propanal of formula (I) under reactive distillation conditions

[0224] In a 0.5 L three-necked reaction flask with a Liebig condenser, a small column and a magnetic stirrer, 160 g (=0.509 mol feed) of 4-isopropyl-1-methylene-2-[1-[2-(2-vinyloxyethoxy)-ethoxy]ethoxy]cyclohexane from Example 1 were weighed out and mixed with 0.67 g of lithium dihydrogen phosphate, 0.67 g of trioctylamine and 160 g of dibenzyl ether. The reaction mixture was then heated to 175° C. at 100 mbar and light volatiles were distilled at the top of the column for 5 hours. After complete conversion, 3-(4-isopropylcyclohexen-1-yl)propanal of the formula (I) was then distilled off from the bottom (at 175° C., 1 mbar). This gave 275.1 g of crude product with a purity of 24.3%.

[0225] Subsequently, 275.1 g (24.3%) of crude 3-(4-isopropylcyclohexen-1-yl)propanal of the formula (I) were purified by distillation on a canned column. 61.5 g of 3-(4-isopropylcyclohexen-1-yl)propanal of the formula (I) were isolated with a purity of 97.8% (74-75° C., at 1.0 mbar; R / D=100 / 1).

[0226] The analytical data correspond to those in the literature (EP 2578671 A1).

[0227] Embodiment 4:

[0228] Synthesis of 4-isopropyl-2-[1-(2-methoxy-1-methyl-ethoxy)ethoxy]-1-methylene-cyclohexane (reaction starting material)

[0229]

[0230] 44.66 g (260 mmol, purity 89.8%) of 5-isopropyl-2-methylene-cyclohexanol and 0.15 g (1.3 mmol) of 85% phosphoric acid were added to a 250 mL three-necked reaction flask with a dropping funnel, a powerful condenser and a magnetic stirrer and heated to 30° C. 61.14 g (520 mol) of 1-methoxy-2-vinyloxypropane were then added so that the temperature did not rise more than 40° C. The reaction was stirred for a further 2.5 hours at the same temperature until complete conversion and then cooled to room temperature. The reaction mixture was then dissolved in 100 mL of tert-butyl methyl ether and stirred with 100 mL of saturated sodium carbonate solution for 10 minutes. Phase separation was performed and the organic phase was washed with 100 mL of saturated sodium carbonate solution. The aqueous phase was extracted once with 100 mL of tert-butyl methyl ether. The organic phases were combined and dried over sodium sulfate and then filtered. Finally, the volatile components, the solvent and the excess 1-methoxy-2-vinyloxypropane were distilled off in vacuo using a bulb apparatus (Sdp. 76-80° C. at p=0.6 mbar). The 74.57 g of the residue obtained in this way were used directly in the subsequent reaction (Example 5) as crude 4-isopropyl-2-[1-(2-methoxy-1-methyl-ethoxy)ethoxy]-1-methylene]cyclohexane (purity 88%).

[0231] The analytical data correspond to those in the literature (EP 2578671 A1).

[0232] Embodiment 5:

[0233] Synthesis of 3-(4-isopropylcyclohexen-1-yl)propanal of formula (I) under reactive distillation conditions

[0234] In a 250 mL three-necked reaction flask with a Liebig condenser, an 8 cm long Vigreux fractionation column and a magnetic stirrer, 74.00 g of 4-isopropyl-2-[1-(2-methoxy-1-methyl-ethoxy)ethoxy]-1-methylenecyclohexane (88% purity) from Example 4 were weighed out and 311 mg of lithium dihydrogen phosphate, 311 mg of trioctylamine and 74 g (71.15 mL) of benzyl ether were added. The reaction mixture was then heated to 175° C. at 430 mbar and light volatiles were distilled at the top of the column for 3 hours. After complete conversion, 3-(4-isopropylcyclohexen-1-yl)propanal of formula (I) was then distilled off from the bottom (124° C., 2.5 mbar). 100.22 g of 3-(4-isopropylcyclohexen-1-yl)propanal of formula (I) were obtained with a purity of 27%.

[0235] The analytical data correspond to those in the literature (EP 2578671 A1).

[0236] Embodiment 6:

[0237] Synthesis of 3-methyl-1,1-bis(3-methylbut-2-enyloxy)but-2-ene (reaction starting material)

[0238]

[0239] In a 4L three-necked reaction flask with a powerful condenser, a magnetic stirrer and a water separator, 1226g (13.95mol) of 3-methylbut-2-ene-1-ol, 4.02g (35mmol) of 85% phosphoric acid and 400g (4.65mol) of 3-methylbut-2-enal were dissolved in 1.6L of cyclohexane. The reaction mixture was then heated to reflux for 30 hours, the resulting water was separated, and the reaction mixture was then cooled to room temperature. The reaction mixture was then dissolved in 500mL of tert-butyl methyl ether and stirred in 800mL of 10% sodium carbonate solution for 10 minutes. Phase separation was performed and the organic phase was washed with 800mL of 5% sodium carbonate solution. The aqueous phase was extracted once with 500mL of tert-butyl methyl ether. The organic phases were combined and dried over sodium sulfate, and then filtered. Volatile components and solvents were removed in vacuo. The crude product was fractionated over a 12 cm Vigreux column (Sdp. 72-107° C. at p=1.2-2.2 mbar). 537 g of 3-methyl-1,1-bis(3-methylbut-2-enyloxy)but-2-ene (purity 79%, yield 53%) obtained in this way were used directly in the subsequent reaction (Example 7).

[0240] The analyzed data correspond to those in the literature.

[0241] Embodiment 7:

[0242] Synthesis of 3,7-dimethylocta-2,6-dienal using a thin film evaporator according to the method of the present invention

[0243]

[0244] The reaction mixture was fed from the storage container via a metering pump above the stirring blades of a thin-film evaporator equipped with cooling and top removal, adjustable setting of the rotor blades, a vacuum pump for setting the pressure and a collecting glass flask at the bottom.

[0245] The rotation speed is set to a stirring speed of 500rpm. The thin film evaporator is heated to T = 230 ° C. In a storage container emptied by a metering pump, 100.00g of 3-methyl-1,1-bis(3-methylbut-2-enyloxy)but-2-ene (79% purity, 331.7mmol) and 1.00g (7.2mmol, 1.0m%) salicylic acid obtained from Example 6 are weighed and stirred. The solution is applied to the thin film evaporator at a rate of 1.5mL / min. During the reaction, light volatiles are distilled off at the top of the column. The product 3,7-dimethylocta-2,6-dienal is enriched at the bottom of the receiving flask. After the reaction is complete, the device is cooled and depressurized. In the receiving flask, 100mL of tert-butyl methyl ether is added to the reaction solution and extracted with 70mL of saturated sodium bicarbonate solution. After phase separation, the organic phase is washed again with 70mL of saturated sodium chloride solution. The phases are then separated, the organic phase is dried over sodium sulfate and then filtered. The solvent is then removed under vacuum. In this way, 57.1 g of a crude product are obtained. The crude product is then distilled using a bulb apparatus (bottom 75-117° C., at 0.6 mbar). 49.5 g of 3,7-dimethylocta-2,6-dienal are isolated with a purity of 74% (242 mmol, yield 73%).

[0246] The analyzed data correspond to those in the literature.

[0247] The comparison of the methods shows that the desired product can be prepared in significantly higher purity using the method according to the invention (see Table 1). The proportion of unwanted by-products is significantly reduced, which shows that the synthesis is more selective and at the same time milder.

[0248] Table 1: Comparison of the reaction products from Example 2 (according to the invention) and Example 3 (reactive distillation).

[0249]

Claims

1. A method for preparing an odorant or fragrance by performing a thermal rearrangement reaction, the method comprising the following steps: a) providing at least one reaction starting material and / or other reagents in a thin film evaporator; b) subjecting the reaction starting materials from step a) to at least one thermal rearrangement reaction under distillation conditions in the thin film evaporator; c) obtaining the odorant or fragrance.

2. The method of claim 1, wherein the at least one thermal rearrangement reaction comprises at least one pericyclic reaction.

3. The method according to any one of claims 1 or 2, comprising at least one rearrangement of the Claisen rearrangement type, the Cope rearrangement type and / or the Prins reaction type.

4. The method according to any one of claims 1 to 3, comprising at least one [3,3]-sigmatropic rearrangement.

5. The method according to any one of claims 1 to 4, further comprising providing at least one acid as a reagent in step a).

6. The method according to any one of claims 1 to 5, further comprising providing salicylic acid as a Claisen-type thermal rearrangement reagent in step a).

7. The process according to any one of claims 1 to 6, wherein the product of step c) is 3-(4-isopropylcyclohexen-1-yl)propanal of formula (I): and its stereoisomers or mixtures thereof.

8. The method according to claim 7, wherein the reaction starting material is selected from acetals of formula (IIa), (IIb) and / or (IIc): Wherein R in the compound of formula (IIa) represents a straight chain or branched chain C 1-20 An alkyl group, a benzyl group, an acetyl group, a phenyl group, -CH2-CH2-OCH3, -CH(CH3)-CH2-OCH3, -(CH2)2-O-(CH2)2-O-CH=CH2, -(CH2)2-O-(CH2)2-O-(CH2)2-O-CH=CH2 or 2-methylene-tetrahydrofuran, and R in the compound of formula (IIc) represents a linear or branched C 1-20 alkyl groups, -(CH2)2-O-(CH2)2- or -(CH2)2-O-(CH2)2-O-(CH2)2-, and their stereoisomers, in particular diastereomers and enantiomers, and mixtures thereof.

9. The method according to claim 7 or 8, wherein the group R of the acetal of formula (IIa) is an ethyl group, a butyl group and -(CH2)2-O-(CH2)2-O-CH=CH2.

10. The process according to any one of claims 7 to 9, further comprising a process step 0) before step a), wherein in step 0), the reaction starting materials of formula (IIa), (IIb) and / or (IIc) are provided via acid-catalyzed addition of 5-isopropyl-2-methylenecyclohexanol to the corresponding vinyl ether of formula (IV): Where R represents a straight chain or branched C 1-20 An alkyl group, a benzyl group, an acetyl group, a phenyl group, -CH2-CH2-OCH3, -CH(CH3)-CH2-OCH3, -(CH2)2-O-(CH2)2-O-CH=CH2, -(CH2)2-O-(CH2)2-O-(CH2)2-O-CH=CH2 or 2-methylene-tetrahydrofuran.

11. The method according to claim 10, wherein the Lewis acid or The acid is used as acid catalyst for the acid-catalyzed addition in step 0).

12. The process according to any one of claims 10 or 11, wherein the vinyl ether of formula (IV) is used in a 1.1 to 5.0-fold molar excess.

13. The process according to any one of claims 10 to 12, wherein the vinyl ether of formula (IV) remaining in the reaction mixture is recovered by distillation.

14. The method according to any one of claims 1 to 13, wherein the method is run as a continuous process.

15. The process according to any one of claims 1 to 14, comprising recovering 5-isopropyl-2-methylenecyclohexanol, other starting compounds and / or unrearranged reaction starting materials.

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