2-cyclododecyl-1-propanol and process for the preparation of the intermediate products required for its synthesis

Abstract

The invention relates to a process for preparing tertiary alcohols of the formula (I), wherein cyclododecanone is converted with an acrylic ester of the formula RO-CO-CH=CH2 in a metal-catalyzed reduction of the aldol reaction, wherein R in the above formula represents a linear or branched C1-C8-alkyl radical or a C1-C8-alkenyl radical or an unsubstituted or substituted phenyl radical. Furthermore, the invention relates to the preparation of 2-cyclododecyl-1-propanol, which comprises the preparation of the tertiary alcohol of the formula (I) and the conversion of the thus prepared tertiary alcohol of the formula (I) into 2-cyclododecyl-1-propanol.

Description

Technical Field

[0001] This invention relates to the preparation of tertiary alcohols of formula (I).

[0002] And 2-cyclododecyl-1-propanol was prepared from this intermediate product. Background Technology

[0003] Commercially important aromatic compound 2-cyclododecyl-1-propanol (also known by the name "Hydroxyambran") is typically prepared from cyclododecone via two to three reaction stages. In the first stage, cyclododecone is converted to a tertiary alcohol by reacting with an alkyl ester of 2-bromopropionate, preferably ethyl 2-bromopropionate, in the presence of zinc (Leformatzky reaction). Water is then separated to produce the corresponding unsaturated ester (a mixture of isomers), which is subsequently reduced to 2-cyclododecyl-1-propanol.

[0004] This method is known from patent application DE 37 03 585 A1.

[0005] Although conventional methods provide the final product 2-cyclododecyl-1-propanol in good yields, the first reaction stage, namely the Lefolmatsky reaction, is not only associated with relatively high material costs, but also requires expensive processing or handling work or costs due to the presence of zinc bromide in the reaction. Summary of the Invention

[0006] Therefore, the object of the present invention is to provide an improved method for preparing intermediates in the synthesis of 2-cyclododecyl-1-propanol, namely, providing a tertiary alcohol from the Lefolmatzky reaction, the method overcoming the aforementioned disadvantages.

[0007] The objective of this invention is achieved by a method for preparing tertiary alcohols having formula (I).

[0008] In this process, acrylates with the formula RO-CO-CH=CH2 are used to convert cyclododecanone into hydroxyl groups under metal catalysis. In formula (I) above, R represents a straight-chain or branched C1-C8-alkyl group or a C1-C8-olefinic group or an unsubstituted or substituted phenyl group.

[0009] Preferably, the reaction is carried out in the presence of silane under copper catalysis.

[0010] In a preferred embodiment, polymethylhydrosiloxane (PMHS) is used as the silane. However, other silanes, such as tetramethylhydrosiloxane, triethoxysilane, or benzylsilane, are also considered.

[0011] Particularly preferred is the use of Cu(OAc)2xH2O as a catalyst.

[0012] In one embodiment of the invention, a phosphine compound is used as a ligand for the catalyst.

[0013] Triphenylphosphine is preferred as the ligand in this study.

[0014] In a preferred embodiment of the invention, a stabilizer is used for the acrylate.

[0015] Here, p-hydroxyanisole is preferably used as a stabilizer for acrylates.

[0016] In another preferred embodiment of the invention, the reaction is carried out in a solvent system.

[0017] Here, the solvent system preferably includes toluene or xylene.

[0018] Preferably, the reaction is carried out at a temperature in the range of -30°C to 80°C, particularly preferably at a temperature in the range of 10°C to 50°C, and especially at a temperature in the range of 20°C to 30°C.

[0019] In a preferred embodiment of the invention, R represents a straight-chain or branched C1-C8-alkyl group or a C1-C8-olefin group, such as a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, tert-butyl group, pentyl group, hexyl group, heptyl group, octyl group, 2-ethylhexyl group, allyl group, or vinyl group. Particularly preferably, R represents an ethyl group, n-butyl group, or 2-ethylhexyl group.

[0020] The present invention also relates to the preparation of 2-cyclododecyl-1-propanol, including the preparation of a tertiary alcohol of formula (I) according to any one of the preceding claims, and the conversion of the tertiary alcohol of formula (I) thus prepared into 2-cyclododecyl-1-propanol.

[0021] Instead of the Lefolmatsky reaction, which is not optimal in terms of material costs and wastewater issues, the present invention utilizes a metal-catalyzed, particularly copper-catalyzed, reduction aldol reaction for the first stage of the synthesis of 2-cyclododecyl-1-propanol.

[0022] The method according to the present invention can be schematically represented as follows:

[0023] As can be seen from the reaction formula above, from cyclododecanone1 With acrylate 2 The reduction of hydroxyl alcohol yields tertiary alcohol (I).

[0024] The tertiary alcohol obtained having formula (I) corresponds to the product of the Lefolmatzky reaction, as described in DE 37 03 585, and is subsequently used to prepare 2-cyclododecyl-1-propanol.

[0025] The tertiary alcohol of formula (I) is stably provided with a conversion rate of more than 75% according to the method of the present invention.

[0026] For the catalytic reduction of aldol, various metal catalysts are considered, such as those based on rhodium, palladium, cobalt, or zinc, as described in the literature for this type of reaction. However, copper catalysts, and especially Cu(OAc)₂xH₂O compounds, have proven particularly advantageous within the scope of this invention.

[0027] The reduction of aldol under copper catalysis is typically carried out in the presence of silanes. However, with other metal catalysts, such as rhodium compounds, the reaction can also be carried out in a hydrogen atmosphere as a reducing agent.

[0028] If the reduced aldol reaction is carried out in the presence of a silane under copper catalysis (as is currently preferred), an acid is typically used to break the O-Si bond of the siloxane compound produced in the intermediate step to obtain a tertiary alcohol having formula (I). However, other reagents, such as fluorides, such as ammonium fluoride or tetrabutylammonium fluoride (TBAF), are also considered for this cleavage reaction. In a particularly preferred embodiment of the invention, HCl, H2SO4, or H3PO4 is used as the acid. However, other acids, such as HNO3 or p-toluenesulfonic acid, may also be used. Alkalis such as sodium hydroxide and potassium hydroxide solutions are also considered if the alkaline environment remains mild, as the tertiary alcohol will decompose under other conditions.

[0029] In a preferred embodiment of the invention, a ligand for the catalyst, such as a bidentate ligand, can be used as described in the literature for the reduction of aldol reactions (Organic Letters, 2005, Vol. 7, No. 19, pp. 4225-4228; Beilstein Journal of Organic Chemistry, 2015, 11, pp. 213-218; Tetrahedron Letters 47, 2006, pp. 1403-1407). The ligand may also be selected from the group consisting of organophosphorus compounds, such as phosphine, diphosphine, diamine, or organophosphites. According to the invention, the use of triphenylphosphine as a ligand has proven particularly advantageous.

[0030] If a solvent system is used, the solvent system preferably includes toluene or xylene and, in a particular embodiment, is composed entirely of it.

[0031] To reduce the undesirable polymerization of acrylates, a stabilizer, preferably p-hydroxyanisole, can be used in a preferred embodiment of the method according to the invention. Alternatively, the undesirable polymerization of acrylates can also be minimized by selecting the appropriate acrylate.

[0032] The tertiary alcohol of formula (I) prepared by the method according to the invention can then be converted into the final product 2-cyclododecyl-1-propanol in a further reaction stage known per se, for example as described in DE 37 03 585 A1. Detailed Implementation

[0033] The method according to the invention is illustrated in more detail by way of the following examples, which are for illustrative purposes only and should not limit the scope of patent protection.

[0034] Example A 2-liter three-necked flask equipped with a magnetic stirrer and a dropping funnel was inert by applying vacuum three times and rinsing with N2. 1070 ml of toluene was added countercurrently with N2, followed by 2.04 g of p-hydroxyanisole, 4.93 g of Cu(OAc)₂xH₂O, and 300 g of (powdered) cyclododecanone. Then, 16.19 g of triphenylphosphine was added.

[0035] Next, 225.3 g of PMHS was slowly added at room temperature using a dropping funnel, and the mixture was stirred at room temperature for 15 minutes.

[0036] Next, the sediment was heated to 30°C and 173g of ethyl acrylate was slowly added dropwise using a dropping funnel. The reaction began after approximately 5g of ethyl acrylate was added, which could be identified by the rise in internal temperature. During the further dropwise addition of ethyl acrylate over a period of 3.5 hours, the internal temperature of the sediment (controlled by a water bath if necessary) was maintained between 25°C and 35°C. After the complete addition of ethyl acrylate, the sediment was stirred at room temperature for another 18 hours.

[0037] To form a polymethylsiloxane compound in the intermediate, 500 ml of concentrated HCl (32%) was added dropwise over a 2-hour period without further treatment to obtain the corresponding tertiary alcohol. The internal temperature was initially increased from 22°C to 25°C. After the addition of hydrochloric acid, the reaction precipitate was stirred at room temperature for 18 hours. The precipitate was then transferred to a separatory funnel to separate the phases.

[0038] To determine the properties, small samples were taken from the tertiary alcohol and analyzed by GC. It was shown that the tertiary alcohol formed was consistent with the tertiary alcohol obtained by the corresponding Lefolmatsky reaction of the tertiary alcohol and ethyl 2-bromopropionate in the presence of zinc according to DE 3703585A1 (Example 1, however without removing water from the tertiary alcohol).

[0039] Characteristic data: In addition to the expected tertiary alcohols, GC-FID confirmed the presence of unconverted cyclododecanone, cyclododecanol, triphenylphosphine, and other unknown substances.

[0040] For the implementation of the invention in its various embodiments, the features disclosed in the foregoing description and claims, whether individually or in any combination, are essential.

Claims

1. A method for preparing tertiary alcohols having formula (I), （I）， Its features are, Acrylates with the formula RO-CO-CH=CH2 are converted into cyclododecanone via a reduction reaction of hydroxyl groups under metal catalysis. Wherein, R represents a straight-chain or branched C1-C8-alkyl group or a C1-C8-olefin group, or represents an unsubstituted or substituted phenyl group. The reaction is carried out in the presence of silane under copper catalysis. In this study, polymethylhydrosiloxane (PMHS) was used as the silane, Cu(OAc)2xH2O was used as the catalyst, and a phosphine compound was used as the ligand for the catalyst.

2. The method according to claim 1, characterized in that, Triphenylphosphine was used as a ligand.

3. The method according to claim 1, characterized in that, A stabilizer is used for the acrylate.

4. The method according to claim 3, characterized in that, p-hydroxyanisole is used as a stabilizer for the acrylate.

5. The method according to claim 1, characterized in that, The reaction is carried out in a solvent system.

6. The method according to claim 5, characterized in that, The solvent system includes toluene or xylene.

7. The method according to claim 1, characterized in that, The reaction is carried out at a temperature ranging from -30°C to 80°C.

8. The method according to claim 7, characterized in that, The reaction is carried out at a temperature ranging from 10°C to 50°C.

9. The method according to claim 8, characterized in that, The reaction is carried out at a temperature in the range of 20°C to 30°C.

10. The method according to claim 1, characterized in that, R represents a straight-chain or branched C1-C8-alkyl group or a C1-C8-olefin group.

11. The method according to claim 10, characterized in that, R represents an ethyl group, a n-butyl group, or a 2-ethylhexyl group. A method for preparing 12,2-cyclododecyl-1-propanol, characterized in that, The tertiary alcohol of formula (I) is prepared according to any one of claims 1-11, and the prepared tertiary alcohol of formula (I) is converted into 2-cyclododecyl-1-propanol.

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