Process for the preparation of dodeca- and cyclododecanone

Abstract

The application discloses a preparation method of dodecene oxide and cyclododecanone. The application provides a preparation method of dodecene oxide as shown in formula B, which comprises the following steps: performing hydrogenation reaction on a compound as shown in formula A in the presence of a catalyst to obtain a compound as shown in formula B; and the catalyst is selected from any one of the following schemes: scheme one: the catalyst is a palladium catalyst and an amine compound; and scheme two: the catalyst is a palladium complex containing an amine compound. The preparation method of dodecene oxide provided by the application does not generate alcohol by-products. The dodecene oxide prepared by the application can be used to efficiently prepare high-purity cyclododecanone.

Description

TECHNICAL FIELD

[0001] The present application relates to a method for preparing epoxy dodecane and cyclododecanone. BACKGROUND

[0002] Cyclododecanone and its derivatives building blocks have a wide range of applications in biomedical, pesticides and material science. However, in the traditional synthesis of cyclododecanone, cyclododecane or cyclododecanol is mainly prepared by selective oxidation (for example, (a) Barton, D. H. R.; Chavasiri, W. Tetrahedron 1994, 50, 19-30; (b) Balavoinea, D.; Barton, D. H. R.; Boivin, J.; Gref, A.; Ozbalik, N.; Rivière, H. Tetrahedron Letters, 1986, 27, 2849-2852; (c) Li Junping et al. CN 106278814 A 2017-01-04). However, these methods usually have poor selectivity, low efficiency and high energy consumption, especially when cyclododecanol is oxidized to prepare cyclododecanone, the product cyclododecanone and the raw material cyclododecanol have similar properties, and the purification of the final product cyclododecanone is difficult, which brings great challenges to the large-scale production of high-purity cyclododecanone.

[0003] Some early theoretical studies have shown that dodecahydropyridine can undergo a rearrangement reaction under the catalysis of metal halide salt to obtain high purity dodecalactone ((a) Zakharkin, L. I., Guseva, V. V., Kamernitskii, D. A., Tsvetkov, V. F., and Likhomanenko, V. A., Zh. Org. Khim. 1990, 26, 1497; (b) Champalbert, J., Guillois, A., Jullien, J., Jullien, R., Lai, N. T., Pascard, C., and Prange, T. Tetrahedron Lett. 1977, 20, 3251; (c) Wilke, G. and Borner, P. W., Ger. 1075601 1960; (d) Filadska, M. and Balbolov, E., J. Mol. Catal. 1992, 73, 157.). These studies have made it possible to some extent to scale up the synthesis of high purity dodecalactone. However, these methods still have the following two shortcomings: 1. The reagents used in the above-mentioned literature reports for the synthesis of dodecahydropyridine are expensive, harsh conditions, poor selectivity, and difficult to scale up production; 2. The current method also has the disadvantages of expensive catalyst, high dosage, high reaction temperature, large amount of solvent, etc., which is difficult to meet the requirements of scale production.

[0004] Patent US 2004181096A12 in 2001 provides a platinum-catalyzed method for preparing dodecalactone, which shows that the dodecanol impurities present in the preparation of dodecahydropyridine (more than 2%) have a significant effect on the rate of rearrangement reaction and the purity of dodecalactone, resulting in a significant decrease in the efficiency of the rearrangement reaction. The disadvantages of the scheme in this patent are: (1) the use of expensive platinum catalyst; (2) the platinum catalyst has low activity for hydrogenation, which requires high reaction temperature (70-140°C) and very high hydrogenation pressure (at least 50 atm), and when the hydrogen pressure is reduced (5 to 10 atm), the selectivity of the reaction system decreases significantly, and various side reactions and impurities increase significantly. These impurities not only affect the speed of the rearrangement reaction, but also increase the difficulty of product purification. In addition, the temperature of the rearrangement reaction in this patent is as high as 200 degrees, which has high energy consumption and high requirements for equipment. Therefore, the method provided in this patent is not suitable for scale production of high purity dodecalactone, and direct application of this technology for industrial production still has high technical requirements and challenges for equipment and facilities.

[0005] Japanese scientists (Sajiki, H.; Hattori, K.; and Hirota, K. Chem. Eur. J. 2000, 6, 2200.) studied a method of selective catalytic hydrogenation of 9,10-epoxy-1,5-cyclododecadiene by a complex of palladium on carbon and ethylenediamine, which produced a mixture of dodecaene oxide (97%) and cyclododecanol (3%) in 93% yield. It is noted that cyclododecanol not only affects the rearrangement reaction of dodecaene oxide to produce high-purity cyclododecanone, but also brings difficulties to the purification of cyclododecanone product. Therefore, this method is also insufficient to support the synthesis of high-purity cyclododecanone, especially large-scale industrial production.

[0006] Therefore, it is of great significance to explore a new method for synthesizing high-purity cyclododecanone, which is cheap and easy to obtain raw materials, efficient and simple, and the catalyst is cheap and easy to obtain with low dosage, mild reaction conditions and suitable for large-scale production. SUMMARY

[0007] The technical problem to be solved by the present application is to overcome the shortcomings of easy generation of by-product cyclododecanol, high energy consumption and high waste during selective hydrogenation of 9,10-epoxy-1,5-cyclododecadiene in the synthesis of cyclododecanone in the prior art. The present application provides a preparation method of dodecaene oxide and cyclododecanone.

[0008] The present application provides a preparation method of dodecaene oxide as shown in formula B, which comprises the following steps: performing hydrogenation reaction of a compound as shown in formula A in the presence of a catalyst to obtain a compound as shown in formula B;

[0009] The catalyst is selected from any of the following schemes:

[0010] Scheme 1: the catalyst is a palladium catalyst and an amine compound;

[0011] Scheme 2: the catalyst is a palladium complex containing an amine compound;

[0012] The amine compound is selected from one or more of 2,2'-bipyridine, "2,2'-bipyridine substituted with 1, 2, 3 or 4 R -1 " and "diamine compound substituted with 1, 2, 3 or 4 R -2 ";

[0013] In the diamine compound substituted with 1, 2, 3 or 4 R -2 , R -2 is connected to the nitrogen atom; and the diamine compound is ethylenediamine, 1,3-propanediamine, 1,4-butanediamine or 1,2-cyclohexanediamine;

[0014] each R -1independently C1-C9alkyl; 20 alkyl, halo, phenyl, benzyloxy, or phenoxy;

[0015] each R -2 independently C1-C9alkyl; 20 alkyl, phenyl, or benzyl;

[0016]

[0017] In the first aspect, the palladium catalyst and the amine compound are added separately to the system. In the second aspect, the palladium complex is a complex formed from a conventional palladium-containing reagent and the amine compound.

[0018] In the hydrogenation reaction, preferably, R -1 In the first aspect, the C1-C9alkyl is C1-C9alkyl. Preferably, the C1-C9alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, i-butyl, t-butyl, pentyl, hexyl, heptyl, octyl, or n-nonyl, for example methyl or ethyl. 20 In the first aspect, the C1-C9alkyl is C1-C9alkyl. Preferably, the C1-C9alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, i-butyl, t-butyl, pentyl, hexyl, heptyl, octyl, or n-nonyl, for example methyl or ethyl.

[0019] In the hydrogenation reaction, preferably, R -1 In the first aspect, the halo is fluorine, chlorine, bromine, or iodine.

[0020] In the hydrogenation reaction, R -2 In the first aspect, the C1-C9alkyl is C1-C9alkyl. Preferably, the C1-C9alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, i-butyl, t-butyl, pentyl, hexyl, heptyl, octyl, or n-nonyl, for example methyl or ethyl. 20 In the first aspect, the C1-C9alkyl is C1-C9alkyl. Preferably, the C1-C9alkyl is methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, i-butyl, t-butyl, pentyl, hexyl, heptyl, octyl, or n-nonyl, for example methyl or ethyl.

[0021] In the hydrogenation reaction, preferably, the amine compound is 2,2'-bipyridine or "2,2'-bipyridine substituted with 1, or 2 R -1 groups".

[0022] In the hydrogenation reaction, preferably, each R -1 is independently C1-C9alkyl.

[0023] In the hydrogenation reaction, preferably, "2,2'-bipyridine substituted with 1, 2, 3, or 4 R -1 groups" is 2,2'-bipyridine substituted with 1 or 2 R -1 groups.

[0024] In the hydrogenation reaction, preferably, each R -1 is the same.

[0025] In the hydrogenation reaction, preferably, each R-2 The same.

[0026] In the hydrogenation reaction, preferably each R -2 is independently C1-C9 alkyl.

[0027] In the hydrogenation reaction, preferably the 2,2'-bipyridine substituted with 2 R -1 is

[0028] In the hydrogenation reaction, preferably the amine compound is selected from one or more of 2,2'-bipyridine, "2,2'-bipyridine substituted with 1, or 2 R -1 ", and "diamine compound substituted with 1 or 2 R -2 "; each R -1 is C1-C9 alkyl or phenyl; and each R -2 is C1-C 20 alkyl or benzyl; more preferably the amine compound is selected from one or more of 2,2'-bipyridine, N,N'-dimethyl-1,2-cyclohexanediamine, tetramethylethylenediamine, N,N-dimethylethylenediamine, N,N'-dimethylethylenediamine, (R,R)-1,2-diphenylethylenediamine, (S,S)-1,2-diphenylethylenediamine, (R,S)-1,2-diphenylethylenediamine, N,N-dimethyl-1,2-cyclohexanediamine, and ; for example, the amine compound is 2,2'-bipyridine, N,N'-dimethyl-1,2-cyclohexanediamine, tetramethylethylenediamine, N,N-dimethylethylenediamine, N,N'-dimethylethylenediamine, or ; for example, the amine compound is 2,2'-bipyridine, N,N'-dimethyl-1,2-cyclohexanediamine, tetramethylethylenediamine, N,N-dimethylethylenediamine, N,N'-dimethylethylenediamine, or

[0029] In the hydrogenation reaction, preferably the palladium catalyst is a divalent palladium catalyst and / or a zerovalent palladium catalyst; preferably the divalent palladium catalyst is Pd(OAc)2, PdBr2, chloro-containing divalent palladium, Pd(OH)2 / C, palladium trifluoroacetate, palladium bis(acetylacetonate) (II), palladium pivalate, one or more of Pd2(dba)3, Pd(dba)2, Pd2(dba)3.CHCl3, Pd(PPh3)4, Pd(PCy3)2, Pd(COD)2, and Pd / C; more preferably, the palladium catalyst is Pd(OAc)2, Pd(OH)2 / C, or a chloro-containing divalent palladium, such as Pd(OH)2 / C.

[0030] In the hydrogenation reaction, preferably, the palladium complex is selected from the group consisting of

[0031] one or more of Pd2(dba)3, Pd(dba)2, Pd2(dba)3.CHCl3, Pd(PPh3)4, Pd(PCy3)2, Pd(COD)2, and Pd / C; more preferably, the palladium catalyst is Pd(OAc)2, Pd(OH)2 / C, or a chloro-containing divalent palladium, such as Pd(OH)2 / C.

[0032] In the hydrogenation reaction, preferably, the molar ratio of the palladium catalyst to the compound of Formula A is 0.000001 to 0.99; more preferably, 0.001 to 0.1, such as 0.02, 0.01, or 0.05.

[0033] In the hydrogenation reaction, preferably, the molar ratio of the palladium catalyst to the compound of Formula A is 0.000001 to 0.99; more preferably, 0.001 to 0.1, such as 0.02, 0.01, or 0.05.

[0034] In the hydrogenation reaction, preferably, the molar ratio of the amine compound to the palladium catalyst is (0.1 to 10): 1, more preferably, (1 to 3): 1, such as 1: 1 or 2: 1.

[0035] In the hydrogenation reaction, the hydrogenation reaction can be carried out in the absence of a solvent or in the presence of a solvent. Preferably, when the hydrogenation reaction is carried out in the presence of a solvent, the molar volume ratio of the compound of Formula A to the solvent is 0.01 to 40 mmol / mL; more preferably, 0.2 to 20 mmol / mL; such as 1 mmol / mL, 2 mmol / mL, 20 mmol / mL, 0.2 mmol / mL, 0.25 mmol / mL, or 1.25 mmol / mL.

[0036] In the hydrogenation reaction, the hydrogenation reaction is carried out in the presence of a solvent, and the solvent is a conventional solvent for such a reaction in the art; preferably, the solvent is one or more of an ether solvent, an aromatic hydrocarbon solvent, an amide solvent, a sulfoxide solvent, and water; preferably, the ether solvent is tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, diethyl ether, dimethyl glycol ether, or 1,4-dioxane; preferably, the aromatic hydrocarbon solvent is toluene; preferably, the amide solvent is N-methylpyrrolidone, N,N-dimethylformamide, 1,3-dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone, or N,N-dimethylacetamide; preferably, the sulfoxide solvent is dimethyl sulfoxide; more preferably, the solvent is one or more of tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, diethyl ether, dimethyl glycol ether, 1,4-dioxane, and toluene, for example, tetrahydrofuran.

[0037] In the hydrogenation reaction, the reaction temperature of the hydrogenation reaction is a conventional reaction temperature for such a reaction in the art, preferably 40-100°C, for example, 50-80°C, and further for example, 50°C or 80°C.

[0038] In the hydrogenation reaction, preferably, the hydrogenation reaction is carried out in the presence of hydrogen gas, and the pressure of the hydrogen gas is 0.001 atm-100 atm, preferably 0.8 atm-10 atm, for example, 1 atm.

[0039] In the hydrogenation reaction, the reaction time of the hydrogenation reaction is related to the reaction scale, and preferably, the reaction time of the hydrogenation reaction is 24-60 h, for example, 24 h, 28 h, 30 h, 48 h, or 60 h.

[0040] The present application also provides a preparation method of cyclododecanone represented by Formula C, which comprises the following steps:

[0041] (1) preparing the compound represented by Formula B according to the preparation method of the compound represented by Formula B as described above;

[0042] (2) subjecting the compound represented by Formula B to a rearrangement reaction as shown below in the presence of a metal salt to obtain a compound represented by Formula C;

[0043]

[0044] In the rearrangement reaction, the reaction conditions of the rearrangement reaction can be conventional reaction conditions for such a reaction in the art.

[0045] In the rearrangement reaction, the rearrangement reaction can be carried out in the absence of a solvent or in the presence of a solvent.

[0046] In the rearrangement reaction, preferably, the metal salt is a metal halide; the metal salt is preferably one or more of LiCl, LiBr, LiI, NaCl, NaBr, NaI, KCl, KBr, KI, MgCl2, MgBr2, MgI2, MgBr2OEt2, and MgI2OEt2; for example, LiBr, LiI, NaI, LiBr, MgBr, MgI2, or MgBr2OEt2.

[0047] In the rearrangement reaction, preferably, the molar ratio of the metal salt to the compound of Formula B is 0.0001 to 0.99; preferably, 0.001 to 0.1, for example, 0.04, 0.02, or 0.05.

[0048] In the rearrangement reaction, the reaction temperature of the rearrangement reaction is a conventional reaction temperature for such reactions in the art, for example, 100 to 180°C, and further for example, 140 to 165°C.

[0049] In the rearrangement reaction, the reaction is carried out in the presence of diglycol dimethyl ether. Preferably, the molar volume ratio of the compound of Formula B to the diglycol dimethyl ether is 1 to 5 mmol / L, for example, 2 mmol / L.

[0050] In the rearrangement reaction, the reaction time of the rearrangement reaction is related to the reaction scale, and preferably, the reaction time of the rearrangement reaction is 4 to 6 h.

[0051] Without departing from the common knowledge in the art, the above-mentioned preferred conditions can be combined arbitrarily, i.e., to obtain each preferred example of the present application.

[0052] The term "halogen" refers to fluorine, chlorine, bromine, or iodine.

[0053] The reagents and raw materials used in the present application are commercially available.

[0054] The positive progress effect of the present application is that:

[0055] The preparation method of the present application can prepare cyclododecanone from 9,10-epoxy-1,5-cyclododecadiene by mild reaction conditions, and both steps can be reacted without solvent, reducing the amount of solvent emission. And there is no alcohol by-product generated in the step of preparing epoxydodecane from 9,10-epoxy-1,5-cyclododecadiene. The epoxydodecane prepared by the present application can be efficiently prepared to cyclododecanone. The cyclododecanone product prepared by the present application has a wide application in biological medicine, pesticide, and material science, etc. DETAILED DESCRIPTION

[0056] The application is further illustrated by the following examples without thereby limiting the application to the examples described. The experimental procedures in the following examples, where no specific conditions are indicated, were carried out according to standard methods and conditions, or according to the instructions of the commercial suppliers.

[0057] Example 1

[0058]

[0059] Example 1 Synthesis of dodeca-1,5-diene oxide using 2,2'-bipyridine (31.2 mg, 0.2 mmol, 2 mol%), 10% Pd(OH)2 / C (280.9 mg, 0.2 mmol, 2 mol%), starting material 9,10-epoxy-1,5-cyclododecadiene (1.78 g, 10 mmol) and THF (10 mL) at 50 °C under 1 atm of hydrogen atmosphere for 24 h gave dodeca-1,5-diene oxide (1.82 g, 100% yield). The reaction mixture was filtered and concentrated to give the product as a colorless transparent liquid. NMR and GC-MS checks showed no dodecanol formation.

[0060] 1 H NMR (400 MHz, CDCI3) δ 2.88-2.68 (m, 2H), 2.14-1.77 (m, 2H), 1.50-0.99 (m, 18H).

[0061] Example 2

[0062]

[0063] Example 2 Synthesis of dodeca-1,5-diene oxide using 2,2'-bipyridine (156 mg, 1 mmol, 2 mol%), 10% Pd(OH)2 / C (1.40 g, 1 mmol, 2 mol%), starting material 9,10-epoxy-1,5-cyclododecadiene (8.92 g, 50 mmol) and THF (50 mL) at 50 °C under 1 atm of hydrogen atmosphere for 28 h gave dodeca-1,5-diene oxide (9.1 g, 99.5% yield). The reaction mixture was filtered and concentrated to give the product as a colorless transparent liquid. NMR and GC-MS checks showed no dodecanol formation, with 0.5% of the starting material 9,10-epoxy-1,5-cyclododecadiene remaining.

[0064] Example 3

[0065]

[0066] Epoxylaural was synthesized using 2,2'-bipyridine (156 mg, 1 mmol, 1 mol%), 10% Pd(OH)2 / C (1.40 g, 1 mmol, 1 mol%), starting material 9,10-epoxy-1,5-cyclododecadiene (17.83 g, 100 mmol) and THF (50 mL) at 50 degrees under 1 atm of hydrogen atmosphere for 48 hours. The reaction was filtered and concentrated to yield the product as a colorless transparent liquid. NMR and GC-MS checks showed no cyclododecanol formation with a conversion yield of >99% of epoxylaural and 25% of the starting material 9,10-epoxy-1,5-cyclododecadiene was recovered.

[0067] Example 4

[0068]

[0069] Epoxylaural was synthesized using 2,2'-bipyridine (156 mg, 1 mmol, 1 mol%), 10% Pd(OH)2 / C (1.40 g, 1 mmol, 1 mol%), starting material 9,10-epoxy-1,5-cyclododecadiene (17.83 g, 100 mmol) and THF (5 mL) at 50 degrees under 1 atm of hydrogen atmosphere for 48 hours. The reaction was filtered and concentrated to yield the product as a colorless transparent liquid. NMR and GC-MS checks showed no cyclododecanol formation with a conversion yield of >99% of epoxylaural and 5% of the starting material 9,10-epoxy-1,5-cyclododecadiene was recovered.

[0070] Example 5

[0071]

[0072] Epoxylaural was synthesized using 2,2'-bipyridine (156 mg, 1 mmol, 1 mol%), 10% Pd(OH)2 / C (1.40 g, 1 mmol, 1 mol%), starting material 9,10-epoxy-1,5-cyclododecadiene (17.83 g, 100 mmol) at 50 degrees under 1 atm of hydrogen atmosphere for 30 hours. The reaction was filtered and concentrated to yield the product as a colorless transparent liquid. NMR and GC-MS checks showed no cyclododecanol formation with a conversion yield of >99% of epoxylaural and 0.25% of the starting material 9,10-epoxy-1,5-cyclododecadiene was recovered.

[0073] Example 6

[0074]

[0075] Example 1

[0076] Example 2

[0077]

[0078] Example 3

[0079] Example 4

[0080]

[0081] Example 5

[0082] Example 6

[0083]

[0084] Using N,N'-dimethylethylenediamine (17.6 mg, 0.2 mmol, 2 mol%), 10% Pd(OH)2 / C (280 mg, 0.2 mmol, 2 mol%), starting material 9,10-epoxy-1,5-cyclododecadiene (1.78 g, 10 mmol) and THF (50 mL) at 50 degrees under 1 atm of hydrogen atmosphere for 24 hours, epoxidodecane was synthesized. The reaction was filtered and concentrated to yield the product as a colorless transparent liquid. NMR and GC-MS checks showed no cyclododecanol formation with a conversion yield of >99% of epoxidodecane and 37% of the starting material 9,10-epoxy-1,5-cyclododecadiene was recovered.

[0085] Example 10

[0086]

[0087] Using 2,2'-bipyridine (156 mg, 1 mmol, 1 mol%), 10% Pd(OH)2 / C (1.40 g, 1 mmol, 1 mol%), starting material 9,10-epoxy-1,5-cyclododecadiene (17.83 g, 100 mmol) at 80 degrees under 1 atm of hydrogen atmosphere for 30 hours, epoxidodecane (18.2 g, 99.7%) was synthesized. The reaction was filtered and concentrated after THF dilution to yield the product as a colorless transparent liquid. NMR and GC-MS checks showed no cyclododecanol formation with 0.25% of the starting material 9,10-epoxy-1,5-cyclododecadiene remaining.

[0088] Example 11

[0089]

[0090] Using the above complex as catalyst (293 mg, 0.5 mmol, 1 mol%), starting material 9,10-epoxy-1,5-cyclododecadiene (8.92 g, 50 mmol), 40 mL THF at 50 degrees under 1 atm of hydrogen atmosphere for 60 hours, epoxidodecane (9.1 g, 99%) was synthesized. The reaction was filtered and concentrated after THF dilution to yield the product as a colorless transparent liquid. NMR and GC-MS checks showed no cyclododecanol formation with 1 % of the starting material 9,10-epoxy-1,5-cyclododecadiene remaining.

[0091] Example 12

[0092]

[0093] Using the above complex of palladium as catalyst (190 mg, 0.5 mmol, 2 mol%), starting material 9,10-epoxy-1,5-cyclododecadiene (4.46 g, 25 mmol), THF 20 mL at 50 degrees, 1 atm of hydrogen atmosphere for 40 hours, epoxylaural (4.51 g, 99%) was synthesized. The reaction mixture was diluted with THF and filtered and concentrated to give the product as a colorless transparent liquid, NMR and GC-MS check showed no cyclododecanol formation, 1 % of starting material 9,10-epoxy-1,5-cyclododecadiene remained unreacted.

[0094] Example 13

[0095]

[0096] Using the above complex of palladium as catalyst (190 mg, 0.5 mmol, 2 mol%), starting material 9,10-epoxy-1,5-cyclododecadiene (4.46 g, 25 mmol), THF 20 mL at 50 degrees, 1 atm of hydrogen atmosphere for 40 hours, epoxylaural (4.51 g, 99%) was synthesized. The reaction mixture was diluted with THF and filtered and concentrated to give the product as a colorless transparent liquid, NMR and GC-MS check showed no cyclododecanol formation, 1 % of starting material 9,10-epoxy-1,5-cyclododecadiene remained unreacted.

[0097] Example 14

[0098]

[0099] Using the above complex of palladium as catalyst (190 mg, 0.5 mmol, 2 mol%), starting material 9,10-epoxy-1,5-cyclododecadiene (4.46 g, 25 mmol), THF 20 mL at 50 degrees, 1 atm of hydrogen atmosphere for 40 hours, epoxylaural (4.51 g, 99%) was synthesized. The reaction mixture was diluted with THF and filtered and concentrated to give the product as a colorless transparent liquid, NMR and GC-MS check showed no cyclododecanol formation, 1 % of starting material 9,10-epoxy-1,5-cyclododecadiene remained unreacted.

[0100] Example 15

[0101]

[0102] Using the above complex as catalyst (183 mg, 0.5 mmol, 5 mol%), starting material 9,10-epoxy-1,5-cyclododecadiene (1.78 g, 10 mmol), 40 mL THF, at 50 degrees, 1 atm of hydrogen atmosphere for 60 hours, synthesis of dodeca-epoxide (1.49 g, 81 %) was obtained. The reaction solution was diluted with THF and filtered and concentrated to obtain the product as a colorless transparent liquid. NMR and GC-MS examination showed no cyclododecanol formation, with a conversion yield of >99% of dodeca-epoxide, and 19% of the starting material 9,10-epoxy-1,5-cyclododecadiene was recovered.

[0103] Example 16

[0104]

[0105] Using the above complex as catalyst (213 mg, 0.5 mmol, 5 mol%), starting material 9,10-epoxy-1,5-cyclododecadiene (1.78 g, 10 mmol), 40 mL THF, at 50 degrees, 1 atm of hydrogen atmosphere for 60 hours, synthesis of dodeca-epoxide (1.47 g, 80%) was obtained. The reaction solution was diluted with THF and filtered and concentrated to obtain the product as a colorless transparent liquid. NMR and GC-MS examination showed no cyclododecanol formation, with a conversion yield of >99% of dodeca-epoxide, and 20% of the starting material 9,10-epoxy-1,5-cyclododecadiene was recovered.

[0106] Example 17

[0107]

[0108] Synthesis of cyclododecanone using LiI (268 mg, 2 mmol, 4 mol%) and dodeca-epoxide (9.1 1 g, 50 mmol, 1.0 equiv) under nitrogen protection, heated to 165 degrees for 6 hours. Dilution with dichloromethane and filtration of lithium iodide salt to obtain 9.1 1 grams of pure product with a yield of 99.9%, the product was a white solid with a melting point of 61 -63 °C. 1 H NMR (400 MHz, CDCI3) δ 2.45-2.42 (m, 4H), 1.69-1.66 (m, 4H), 1.28 (m, 14H). 13 C NMR (100 MHz, CDCI3) δ 213.0, 40.3, 24.6, 24.5, 24.2, 22.5, 22.3.

[0109] Example 18

[0110]

[0111] Cyclododecanone was synthesized using LiI (134 mg, 1 mmol, 2 mol%), and dodecylene oxide (9.11 g, 50 mmol, 1.0 equiv) under nitrogen protection, heating to 165 degrees for 6 hours. Purification by silica gel column chromatography gave 8.2 grams of pure product, with 0.91 grams of raw material recovered, a product yield of 90%, the product being a white solid with a melting point of 60-62 °C.

[0112] Example 19

[0113]

[0114] Cyclododecanone was synthesized using LiI (134 mg, 1 mmol, 2 mol%), and dodecylene oxide (9.11 g, 50 mmol, 1.0 equiv) under nitrogen protection, heating to 165 degrees for 6 hours. Purification by silica gel column chromatography gave 8.2 grams of pure product, with 0.91 grams of raw material recovered, a product yield of 90%, the product being a white solid with a melting point of 60-62 °C.

[0115] Example 20

[0116]

[0117] Cyclododecanone was synthesized using LiBr (87 mg, 1 mmol, 5 mol%), diglyme (10 mL) and dodecylene oxide (3.64 g, 20 mmol, 1.0 equiv) under nitrogen protection, heating to 140 degrees for 4 hours. Purification by silica gel column chromatography gave 3.0 grams of pure product, a product yield of 82%, the product being a white solid with a melting point of 59-60 °C.

[0118] Example 21

[0119]

[0120] Cyclododecanone was synthesized using NaI (150 mg, 1 mmol, 5 mol%), diglyme (10 mL) and dodecylene oxide (3.64 g, 20 mmol, 1.0 equiv) under nitrogen protection, heating to 140 degrees for 4 hours. Purification by silica gel column chromatography gave 2.84 grams of pure product, a product yield of 78%, the product being a white solid with a melting point of 59-60 °C.

[0121] Example 22

[0122]

[0123] Cyclododecanone was synthesized using MgBr2(184 mg, 1 mmol, 5 mol%), diglyme (10 mL) and dodecylene oxide (3.64 g, 20 mmol, 1.0 equiv) under nitrogen protection, heating to 140 degree for 4 hours. Purification by silica gel column chromatography gave 2.73 g of pure product in 75% yield as a white solid with a melting point of 59-60 °C.

[0124] Example 23

[0125]

[0126] Cyclododecanone was synthesized using MgBr2(184 mg, 1 mmol, 5 mol%), diglyme (10 mL) and dodecylene oxide (3.64 g, 20 mmol, 1.0 equiv) under nitrogen protection, heating to 140 degree for 4 hours. Purification by silica gel column chromatography gave 2.73 g of pure product in 75% yield as a white solid with a melting point of 59-60 °C.

[0127] Example 24

[0128]

[0129] Cyclododecanone was synthesized using MgBr2(184 mg, 1 mmol, 5 mol%), diglyme (10 mL) and dodecylene oxide (3.64 g, 20 mmol, 1.0 equiv) under nitrogen protection, heating to 140 degree for 4 hours. Purification by silica gel column chromatography gave 2.73 g of pure product in 75% yield as a white solid with a melting point of 59-60 °C.

[0130] All documents referred to in this disclosure are incorporated herein by reference as if each were individually incorporated by reference. In addition, it is to be understood that the application can be carried out by specifically different embodiments and that embodiments can be practiced without materials details and / or conditions of practice not specifically set forth herein. This disclosure is not to be limited in scope by the specific embodiments described herein. It is to be understood that the application is not limited in scope by the specific embodiments described herein, which are intended as illustrations only. Numerous modifications, in addition to those described herein, will become apparent to those skilled in the art. The application is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The application is capable of other embodiments and of being practiced or carried out in various ways.

Claims

1. A process for the preparation of dodecahydro-m-cyclodextran as shown in formula B, characterized in that, It comprises the following steps: in the presence of a catalyst, a compound as shown in formula A is subjected to hydrogenation reaction as shown in the following formula to obtain a compound as shown in formula B; The catalyst is selected from any of the following schemes: Scheme 1: the catalyst is a palladium catalyst and an amine compound; Scheme 2: the catalyst is a palladium complex containing an amine compound; The amine compound is selected from one or more of 2,2'-bipyridine, "substituted 2,2'-bipyridine" and "substituted diamine compound" -1 substituted 2,2'-bipyridine" and "substituted diamine compound" -2 substituted 2,2'-bipyridine" and "substituted diamine compound" said substituted diamine compound is substituted with 1, 2, or 3 R -2 substituted diamine compound, R -2 attached to the nitrogen atom; said diamine compound is ethylenediamine or 1,2-cyclohexanediamine; Each R -1 Independently C1~C 20 Alkyl, halogen, phenyl, benzyloxy, or phenoxy; Each R -2 Independently C1~C 20 Alkyl, phenyl, or benzyl; The palladium catalyst is a divalent palladium catalyst; 。 2. The method of claim 1, wherein the dodecaepoxide is prepared according to Formula B, ###0001### B R -1 In particular, the C1-C4alkyl is methyl. 20 alkyl is C1-C9alkyl; and / or, R -1 In some embodiments, the halogen is fluorine, chlorine, bromine, or iodine. and / or, R -2 In particular, the C1-C6alkyl is methyl. 20 In particular, the C1-C9alkyl is methyl. and / or, said "substituted 2,2'-bipyridine" is a 2,2'-bipyridine substituted with 1, 2, 3, or 4 R -1 substituted 2,2'-bipyridine" is a 2,2'-bipyridine substituted with 1 or 2 R -1 substituted 2,2'-bipyridine" is a 2,2'-bipyridine substituted with 1 or 2 R 3. The method of claim 2, wherein the dodecaepoxide is prepared according to the following formula B: ###0002### B R -1 In the C1-C9alkyl group, the C1-C9alkyl group is a methyl group, an ethyl group, a n-propyl group, an i-propyl group, a n-butyl group, a sec-butyl group, an i-butyl group, a t-butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, or a nonyl group. and / or, R -2 In the C1-C9alkyl group, the C1-C9alkyl group is a methyl group, an ethyl group, a n-propyl group, an i-propyl group, a n-butyl group, a sec-butyl group, an i-butyl group, a t-butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, or a nonyl group.

4. The method of claim 3, wherein the dodecaepoxide is prepared according to Formula B, ###0002### B R -1 In particular, the C1-C9alkyl group is a methyl group, an ethyl group or a n- nonyl group. and / or, R -2 In some embodiments, the C1-C9alkyl is methyl or ethyl.

5. The method of claim 2, wherein the dodecaepoxide is prepared according to the following formula B: ###0002### B In the hydrogenation reaction, each R -1 are the same; And / or, each R -2 same; And / or, each R -2 Independently, it is a C1~C9 alkyl group; And / or, each R -1 Independently, it is a C1~C9 alkyl group; and / or, said 2 R -1 substituted 2,2'-bipyridines are ; and / or the divalent palladium catalyst is one or more of Pd(OAc)2, PdBr2, chloro-containing divalent palladium, Pd(OH)2 / C, palladium trifluoroacetate, palladium bis(acetylacetonate), palladium pivalate, and one or more of Pd(OAc)2, PdBr2, chloro-containing divalent palladium, Pd(OH)2 / C, palladium trifluoroacetate, palladium bis(acetylacetonate), palladium pivalate, 6. The method of claim 5, wherein the dodecaepoxide is prepared according to the following formula B: ###0002### B The amine compound is 2,2'-dipyridyl or "2,2'-dipyridyl substituted by 1 or 2 R -1 substituted 2,2'-dipyridyl"; And / or, the chlorine-containing divalent palladium is dichlorobis(tricyclohexylphosphine)palladium, allylpalladium(II) chloride dimer, [1,3-bis(diphenylphosphinopropane]palladium chloride, 1,2-bis(diphenylphosphino)ethane dichloropalladium(II), (1,5-cyclooctadiene)dichloropalladium(II), dichloropalladium, PdCl2(dppf), PdCl2(PPh3)2, PdCl2(Xantphos), [PdCl(C3H5)]2, PdCl2(MeCN)2 or PdCl2(PhCN).

7. The method of claim 1, wherein the dodecaepoxide is prepared according to the following formula B: ###0002### B The amine compound is selected from one or more of 2,2'-bipyridine, "2,2'-bipyridine substituted with 1 or 2 R -1 groups," and "diamine compound substituted with 1 or 2 R -2 groups;" each R -1 is C1-C9alkyl or phenyl; each R -2 is C1-C 20 alkyl or benzyl. and / or, the palladium complex is selected from one or more of , , and . And / or, the palladium catalyst is Pd(OAc)2, Pd(OH)2 / C or chlorine-containing divalent palladium.

8. The method of claim 7, wherein the dodecaepoxide is prepared according to the following formula B: ###0002### B The amine compound is selected from one or more of 2,2'-dipyridyl, N,N'-dimethyl-1,2-cyclohexanediamine, N,N-dimethylethylenediamine, N,N'-dimethylethylenediamine, (R,R)-1,2-diphenylethylenediamine, (S,S)-1,2-diphenylethylenediamine, (R,S)-1,2-diphenylethylenediamine, N,N-dimethyl-1,2-cyclohexanediamine, and N,N'-dimethylethylenediamine. And / or, the palladium catalyst is Pd(OH)2 / C.

9. The method of claim 8, wherein the dodecaepoxide is prepared according to the following formula B: ###0002### B The amine compound is 2,2'-dipyridyl, N,N'-dimethyl-1,2-cyclohexanediamine, N,N-dimethylethylenediamine, N,N'-dimethylethylenediamine, or .

10. The method of claim 9, wherein the dodecaepoxide is prepared according to the following formula B: ###0002### B The amine compound is 2,2'-dipyridyl, N,N'-dimethyl-1,2-cyclohexanediamine, N,N-dimethylethylenediamine or N,N'-dimethylethylenediamine.

11. The method of claim 1, wherein the dodecaepoxide is prepared according to the following formula B: ###0001### B The molar ratio of the palladium catalyst to the compound as shown in formula A is 0.000001-0.99; And / or, the molar ratio of the complex to the compound as shown in formula A is 0.000001-0.99; And / or, the molar ratio of the amine compound to the palladium catalyst is (0.1-10):

1. And / or, the hydrogenation reaction is carried out in the absence or presence of a solvent. And / or, the reaction temperature of the hydrogenation reaction is 40-100℃. And / or, the hydrogenation reaction is carried out in the presence of hydrogen; the pressure of the hydrogen is 0.001 atm-100 atm. And / or, the reaction time of the hydrogenation reaction is related to the reaction scale.

12. The method of claim 11, wherein the dodecaepoxide is prepared according to Formula B, ###0002### B The molar ratio of the palladium catalyst to the compound as shown in formula A is 0.001-0.1; And / or, the molar ratio of the complex to the compound as shown in formula A is 0.001-0.1; And / or, the molar ratio of the amine compound to the palladium catalyst is (1-3):

1. And / or, the reaction temperature of the hydrogenation reaction is 50-80℃. And / or, the hydrogenation reaction is carried out in the presence of hydrogen; the pressure of the hydrogen is 0.8 atm-10 atm. And / or, the reaction time of the hydrogenation reaction is related to the reaction scale, and the reaction time of the hydrogenation reaction is 24-60 h.

13. The method of claim 12, wherein the dodecaepoxide is prepared according to Formula B, ###00002### B The molar ratio of the palladium catalyst to the compound as shown in formula A is 0.02, 0.01 or 0.05; And / or, the molar ratio of the complex to the compound as shown in formula A is 0.02, 0.01 or 0.05; And / or, the molar ratio of the amine compound to the palladium catalyst is 1:1 or 2:

1. and / or, the hydrogenation reaction is carried out at a temperature of 50°C or 80°C; and / or, the hydrogenation reaction is carried out in the presence of hydrogen; the pressure of the hydrogen is 1 atm; and / or, the reaction time of the hydrogenation reaction is related to the reaction scale; the reaction time of the hydrogenation reaction is 24 h, 28 h, 30 h, 48 h or 60 h.

14. The method of claim 13, wherein the dodecaepoxide is prepared according to Formula B, ###0002### B when the hydrogenation reaction is carried out in the presence of a solvent, the molar volume ratio of the compound of formula A to the solvent is 0.01-40 mmol / mL; and / or, when the hydrogenation reaction is carried out in the presence of a solvent, the solvent is one or more of an ether solvent, an aromatic hydrocarbon solvent, an amide solvent, a sulfoxide solvent and water.

15. The method of claim 14, wherein the dodecaepoxide is prepared according to Formula B, ###0002### B when the hydrogenation reaction is carried out in the presence of a solvent, the molar volume ratio of the compound of formula A to the solvent is 0.2-20 mmol / mL; and / or, when the hydrogenation reaction is carried out in the presence of a solvent, the ether solvent is tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, diethyl ether, dimethyl glycol ether or 1,4-dioxane; the aromatic hydrocarbon solvent is toluene; the amide solvent is N-methylpyrrolidone, N,N-dimethylformamide, 1,3-dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone or N,N-dimethylacetamide; the sulfoxide solvent is dimethyl sulfoxide.

16. The method of claim 15, wherein the dodecaepoxide is prepared according to Formula B, ###0002### B when the hydrogenation reaction is carried out in the presence of a solvent, the molar volume ratio of the compound of formula A to the solvent is 1 mmol / mL, 2 mmol / mL, 20 mmol / mL, 0.2 mmol / mL, 0.25 mmol / mL or 1.25 mmol / mL; and / or, when the hydrogenation reaction is carried out in the presence of a solvent, the solvent is one or more of tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, diethyl ether, dimethyl glycol ether, 1,4-dioxane and toluene.

17. The method of claim 16, wherein the dodecaepoxide is prepared according to Formula B, ###00002### B when the hydrogenation reaction is carried out in the presence of a solvent, the solvent is tetrahydrofuran.

18. A preparation method of cyclododecanone of formula C, comprising the following steps: (1) preparing the compound of formula B according to the preparation method of the compound of formula B in any one of claims 1-17; (2) subjecting the compound of formula B to a rearrangement reaction as shown below in the presence of a metal salt to obtain the compound of formula C; 。 19. The preparation method of cyclododecanone of formula C according to claim 18, wherein the rearrangement reaction is carried out in the absence of a solvent or in the presence of a solvent; and / or, the metal salt is a metal halide; and / or, the molar ratio of the metal salt to the compound of formula B is 0.0001-0.99; and / or, the reaction temperature of the rearrangement reaction is 100-180°C; and / or, the reaction time of the rearrangement reaction is 4-6 h.

20. The method of claim 19, wherein the molar ratio of the metal salt to the compound of formula B in the rearrangement reaction is 0.001 to 0.

1. and / or, the metal salt is one or more of LiCl, LiBr, Lil, NaCl, NaBr, Nal, KC1, KBr, KI, MgCl2, MgBr2, MgI2, MgBr2OEt2, and MgI2OEt2. and / or, the rearrangement reaction is carried out at a temperature of 140 to 165 °C. and / or, the rearrangement reaction is carried out in the presence of diglycol dimethyl ether.

21. The method of claim 20, wherein the molar ratio of the metal salt to the compound of formula B in the rearrangement reaction is 0.04, 0.02, or 0.

05. and / or, the metal salt is LiBr, Lil, Nal, LiBr, MgBr, MgI2, or MgBr2OEt2. and / or, the rearrangement reaction is carried out in the presence of diglycol dimethyl ether; and the molar volume ratio of the compound of formula B to the diglycol dimethyl ether is 1 to 5 mmol / L.

22. The method of claim 21, wherein the rearrangement reaction is carried out in the presence of diglycol dimethyl ether; and the molar volume ratio of the compound of formula B to the diglycol dimethyl ether is 2 mmol / L.

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