CN115124491A - Preparation method of cyclododecane oxide and cyclododecanone - Google Patents

Abstract

The invention discloses a preparation method of cyclododecane oxide and cyclododecanone. The invention provides a preparation method of epoxy dodecane shown in a formula B, which comprises the following steps: in the presence of a catalyst, carrying out hydrogenation reaction on a compound shown as a formula A as shown in the following formula to obtain a compound shown as a formula B; the catalyst is selected from any one of the following schemes: the first scheme is as follows: the catalyst is a palladium catalyst and an amine compound; scheme two; the catalyst is a palladium complex containing an amine compound. The preparation method of the epoxy dodecane does not generate alcohol byproducts. The epoxy dodecane prepared by the method can be efficiently prepared to obtain high-purity cyclododecanone.

Description

A kind of preparation method of epoxy dodecane and cyclododecanone

technical field

The present invention relates to a preparation method of epoxydodecane and cyclododecanone.

Background technique

Cyclododecanone and its derivative building blocks are widely used in biomedicine, pesticide and material science. However, in the traditional method of synthesizing cyclododecanone, it is mainly obtained from cyclododecane or cyclododecanol by selective oxidation (eg, (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 Jun Equality CN 106278814 A 2017-01-04). However, these methods usually have poor selectivity, low efficiency and high energy consumption, especially when cyclododecanone is prepared by oxidation of cyclododecanol, the properties of the product cyclododecanone and the raw material cyclododecanol are similar, and the final product cyclododecanone has similar properties. There are certain difficulties in the purification of cyclododecanone, which brings great challenges to the large-scale production of high-purity cyclododecanone.

Some early theoretical studies have shown that dodecane oxide can undergo rearrangement reactions catalyzed by metal halide salts to give high-purity cyclododecanones ((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 provide the possibility for the large-scale synthesis of high-purity cyclododecanone to a certain extent. However, these methods still have the following two deficiencies: 1. the above-mentioned literature reports that the reagents used in the synthesis of epoxy dodecane are expensive, harsh conditions, poor selectivity, and difficult to carry out large-scale production; 2. the current method is also There are disadvantages such as expensive catalyst, high dosage, high reaction temperature, large amount of solvent, etc., and it is difficult to meet the requirements of large-scale production.

The patent US 2004181096A12 of 2001 provides a method for preparing cyclododecanone catalyzed by platinum. The research shows that: the cyclododecanol impurities (over 2%) existing in the process of preparing epoxydodecane have a negative effect on the rearrangement reaction The effect on the rate of cyclododecanone and the purity of the prepared cyclododecanone is significant, resulting in a significant decrease in the efficiency of the rearrangement reaction. The disadvantages of the solution in this patent are: (1) expensive noble metal platinum catalysts are used; (2) platinum catalysts have low catalytic hydrogenation activity, specifically, a relatively high reaction temperature (70-140° C.) and high The hydrogenation pressure (at least 50 atmospheres), when the hydrogen pressure is reduced (5 to 10 atmospheres), 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, the energy consumption is high and the equipment requirements are high. Therefore, the method provided by this patent is not yet suitable for large-scale production of high-purity cyclododecanone, and there are still high technical requirements and challenges in equipment and facilities by directly applying this technology for industrial production.

Japanese scientists (Sajiki, H.; Hattori, K.; and Hirota, K.Chem.Eur.J.2000, 6, 2200.) studied the selective catalytic hydrogenation of a complex of palladium/carbon and ethylenediamine The method of 9,10-epoxy-1,5-cyclododecadiene which produces epoxydodecane (97%) and cyclododecane (3%) in 93% yield mixture. It is noted that cyclododecanol will not only affect the rearrangement of epoxydodecane to prepare high-purity cyclododecanone, but also bring difficulties to the purification of cyclododecanone product. Therefore, this method is also insufficient to support the synthetic requirements of high-purity cyclododecanone, especially for large-scale industrial production.

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

SUMMARY OF THE INVENTION

The technical problem to be solved by the present invention is to overcome in the prior art cyclododecanone synthesis process, 9,10-epoxy-1,5 cyclododecadiene is prone to generate cycloalcohol by-products during selective hydrogenation, and the energy consumption is high And three wastes and high disadvantages. The invention provides a preparation method of epoxydodecane and cyclododecanone.

The present invention provides a preparation method of epoxydodecane shown in formula B, which comprises the following steps: in the presence of a catalyst, the compound shown in formula A is subjected to the hydrogenation reaction shown in the following formula to obtain the formula shown in formula B compound;

Described catalyst is selected from following any scheme:

Scheme one: the catalyst is a palladium catalyst and an amine compound;

Scheme 2; Described catalyst is the palladium complex containing amine compound;

The amine compound is selected from 2,2'-bipyridine, "2,2'-bipyridine substituted by 1, 2, 3 or 4 R ^-1 " and "substituted by 1, 2, 3 or 4 R-1" One or more of R ^-2 substituted diamine compounds";

In the diamine compound substituted by 1, 2, 3 or 4 R ^-2 , R ^-2 is connected to the nitrogen atom; the diamine compound is ethylenediamine, 1,3-propanediamine, 1,4-Butanediamine or 1,2-cyclohexanediamine;

each R ^-1 is independently C ₁ -C ₂₀ alkyl, halogen, phenyl, benzyloxy or phenoxy;

Each R ^-2 is independently C ₁ -C ₂₀ alkyl, phenyl or benzyl;

In the scheme one, the palladium catalyst and the amine compound are respectively added to the system; in the scheme two, the palladium complex is a conventional palladium-containing reagent and the The amine compound is the complex formed by the raw material.

In the hydrogenation reaction, preferably, in R ^-1 , the C ₁ -C ₂₀ alkyl group is a C ₁ -C ₉ alkyl group; preferably, the C ₁ -C ₉ alkyl group is a C 1 -C 9 alkyl group Methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl or n-nonyl, e.g. methyl, ethyl base or n-nonyl.

In the hydrogenation reaction, preferably, in R ^-1 , the halogen can be fluorine, chlorine, bromine or iodine.

In the hydrogenation reaction, in R ^-2 , the C ₁ -C ₂₀ alkyl group is a C ₁ -C ₉ alkyl group; preferably, the C ₁ -C ₉ alkyl group is methyl, ethyl , n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl or nonyl, eg methyl or ethyl.

In the hydrogenation reaction, preferably, the amine compound is 2,2'-bipyridine or "2,2'-bipyridine substituted by 1 or 2 R ^-1 ".

In the hydrogenation reaction, preferably, each R ^-1 is independently a C ₁ -C ₉ alkyl group.

In the hydrogenation reaction, preferably, "2,2'-bipyridine substituted by 1, 2, 3 or 4 R ^-1 " is 2,2'-bipyridine substituted by 1 or 2 R ^-1 Bipyridine.

In the hydrogenation reaction, preferably, each R ^-1 is the same.

In the hydrogenation reaction, preferably, each R ^-2 is the same.

In the hydrogenation reaction, preferably, each R ^-2 is independently a C ₁ -C ₉ alkyl group.

In the hydrogenation reaction, preferably, the 2,2'-bipyridine substituted by 2 R ^-1 is

中的一种或多种；例如，所述的胺类化合物为2,2’-联吡啶、N,N'-二甲基-1,2-环己二胺、四甲基乙二胺、N,N-二甲基乙二胺、N,N’-二甲基乙二胺或

还例如，所述的胺类化合物为2,2’-联吡啶、N,N'-二甲基-1,2-环己二胺、四甲基乙二胺、N,N-二甲基乙二胺或N,N’-二甲基乙二胺。In the hydrogenation reaction, preferably, the amine compound is selected from 2,2'-bipyridine, "2,2'-bipyridine substituted by 1 or 2 R ^-1 " and "2,2'-bipyridine substituted by 1 or 2 R-1". One or more of 1 or 2 R ^-2 substituted diamine compounds"; each R ^-1 is C ₁ -C ₉ alkyl or phenyl; each R ^-2 is C ₁ -C ₂₀ alkyl or Benzyl; more preferably, the amine compound is selected from 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-diphenyl Ethylenediamine, (R,S)-1,2-diphenylethylenediamine, N,N-dimethyl-1,2-cyclohexanediamine and

One or more of; for example, the amine compounds are 2,2'-bipyridine, N,N'-dimethyl-1,2-cyclohexanediamine, tetramethylethylenediamine, N,N-dimethylethylenediamine, N,N'-dimethylethylenediamine or

In another example, the amine compounds are 2,2'-bipyridine, N,N'-dimethyl-1,2-cyclohexanediamine, tetramethylethylenediamine, N,N-dimethylamine Ethylenediamine or N,N'-dimethylethylenediamine.

中的一种或多种；所述的含氯二价钯优选为二氯二(三环己基瞵)钯、氯化烯丙基钯(II)二聚物、[1,3-双二苯基磷丙烷]氯化钯、1,2-二(二苯基膦基)乙烷二氯化钯(II)、(1,5-环辛二烯)二氯化钯(II)、二氯化钯、PdCl₂(dppf)、PdCl₂(PPh₃)₂、PdCl₂(Xantphos)、[PdCl(C₃H₅)]₂、PdCl₂(MeCN)₂或PdCl₂(PhCN)；所述的零价钯催化剂优选为Pd₂(dba)₃、Pd(dba)₂、Pd₂(dba)₃.CHCl₃、Pd(PPh₃)₄、Pd(PCy₃)₂、Pd(COD)₂和Pd/C中的一种或多种；更佳地，所述的钯催化剂为Pd(OAc)₂、Pd(OH)₂/C或含氯二价钯，例如Pd(OH)₂/C。In the hydrogenation reaction, preferably, the palladium catalyst is a divalent palladium catalyst and/or a zerovalent palladium catalyst; the divalent palladium catalyst is preferably Pd(OAc) ₂ , PdBr ₂ , chlorine-containing divalent palladium catalyst Valence palladium, Pd(OH) ₂ /C, palladium trifluoroacetate, bis(acetylacetonate) palladium(II), palladium pivalate,

One or more in; Described chlorine-containing divalent palladium is preferably dichlorobis(tricyclohexyl) palladium, chloride allylpalladium (II) dimer, [1,3-bis-diphenylene] phosphopropane]palladium chloride, 1,2-bis(diphenylphosphino)ethanedichloropalladium(II), (1,5-cyclooctadiene)palladium(II) dichloride, dichloro Palladium, PdCl ₂ (dppf), PdCl ₂ (PPh ₃ ) ₂ , PdCl ₂ (Xantphos), [PdCl (C ₃ H ₅ )] ₂ , PdCl ₂ (MeCN) ₂ or PdCl ₂ (PhCN); described The zerovalent palladium catalyst is preferably Pd ₂ (dba) ₃ , Pd(dba) ₂ , Pd ₂ (dba) ₃ .CHCl ₃ , Pd(PPh ₃ ) ₄ , Pd(PCy ₃ ) ₂ , Pd(COD) ₂ and Pd One or more of /C; more preferably, the palladium catalyst is Pd(OAc) ₂ , Pd(OH) ₂ /C or chlorine-containing divalent palladium, such as Pd(OH) ₂ /C.

In the described hydrogenation reaction, preferably, the palladium complex is selected from

中的一种或多种。

one or more of.

In the hydrogenation reaction, preferably, the molar ratio of the palladium catalyst to the compound represented by formula A is 0.000001-0.99; preferably 0.001-0.1, such as 0.02, 0.01 or 0.05.

In the hydrogenation reaction, preferably, the molar ratio of the complex to the compound represented by formula A is 0.000001-0.99; preferably 0.001-0.1, such as 0.02, 0.01 or 0.05.

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

In the hydrogenation reaction, the hydrogenation reaction can be carried out without 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 shown in formula A to the solvent is 0.01-40 mmol/mL; preferably 0.2-20 mmol/mL; For example 1 mmol/mL, 2 mmol/mL, 20 mmol/mL, 0.2 mmol/mL, 0.25 mmol/mL or 1.25 mmol/mL.

In the described hydrogenation reaction, when the described hydrogenation reaction is carried out in the presence of a solvent, the solvent is a conventional solvent for this type of reaction in the field; preferably, the solvent is an ether solvent, an aromatic hydrocarbon solvent , one or more of amide solvents, sulfoxide solvents and water; the ether solvents are preferably tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, diethyl ether, dimethyl ethylene glycol or 1,4-dioxane; the aromatic hydrocarbon solvent is preferably toluene; the amide solvent is preferably N-methylpyrrolidone, N,N-dimethylformamide, 1,3-dimethylformamide -3,4,5,6-tetrahydro-2-pyrimidinone or N,N-dimethylacetamide; the sulfoxide solvent is preferably dimethyl sulfoxide; more preferably, the solvent is One or more of tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, diethyl ether, dimethyl ether, 1,4-dioxane, and toluene, such as tetrahydrofuran.

In the hydrogenation reaction, the reaction temperature of the hydrogenation reaction is the conventional reaction temperature of this type of reaction in the art, preferably 40-100°C, for example 50-80°C, and also for example 50°C or 80°C.

In the hydrogenation reaction, preferably, the hydrogenation reaction is carried out in the presence of hydrogen, and the pressure of the hydrogen is 0.001 atm to 100 atm, preferably 0.8 atm to 10 atm, such as 1 atm.

In the hydrogenation reaction, the reaction time of the hydrogenation reaction is related to the reaction scale. Preferably, the reaction time of the hydrogenation reaction is 24-60h, such as 24h, 28h, 30h, 48h or 60h.

The present invention also provides a kind of preparation method of cyclododecanone shown in formula C, it comprises the steps:

(1) According to the above-mentioned preparation method of the compound shown in formula B, the compound shown in formula B is prepared;

(2) in the presence of a metal salt, the compound shown in the formula B carries out the rearrangement reaction shown below to obtain the compound shown in the formula C;

In the rearrangement reaction, the reaction conditions of the rearrangement reaction can be the conventional reaction conditions of this type of reaction in the art.

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

In the rearrangement reaction, preferably, the metal salt is a metal halide salt; the metal salt is preferably LiCl, LiBr, LiI, NaCl, NaBr, NaI, KCl, KBr, KI, MgCl ₂ , One or more of MgBr ₂ , MgI ₂ , MgBr ₂ OEt ₂ and MgI ₂ OEt ₂ ; for example LiBr, LiI, NaI, LiBr, MgBr, MgI ₂ or MgBr ₂ OEt ₂ .

In the rearrangement reaction, preferably, the molar ratio of the metal salt to the compound represented by formula B is 0.0001-0.99; preferably 0.001-0.1, such as 0.04, 0.02 or 0.05.

In the rearrangement reaction, the reaction temperature of the rearrangement reaction is a conventional reaction temperature of this type of reaction in the art, for example, 100-180°C, and for example, 140-165°C.

In the rearrangement reaction, the reaction is carried out in the presence of diglyme. Preferably, the molar volume ratio of the compound represented by formula B to the diglyme is 1-5 mmol/L, for example, 2 mmol/L.

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 4-6h.

On the basis of not violating common knowledge in the art, the above preferred conditions can be combined arbitrarily to obtain preferred examples of the present invention.

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

The reagents and raw materials used in the present invention are all commercially available.

The positive progressive effect of the present invention is:

The preparation method of the present invention can prepare cyclododecanone by hydrogenation of 9,10-epoxy-1,5-cyclododecadiene under mild reaction conditions, and the two-step reactions can be carried out without solvent, reducing the need for Solvent emissions. And no alcohol by-products are generated in the step of preparing epoxydodecane by hydrogenation of 9,10-epoxy-1,5-cyclododecadiene. The epoxydodecane prepared by the present invention can efficiently prepare cyclododecanone. The cyclododecanone product prepared by the invention has wide application in biological medicine, pesticide and material science and the like.

Detailed ways

The present invention is further described below by way of examples, but the present invention is not limited to the scope of the described examples. The experimental methods that do not specify specific conditions in the following examples are selected according to conventional methods and conditions, or according to the product description.

Example 1

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) were reacted at 50°C under 1 atm hydrogen atmosphere for 24 hours to synthesize dodecane oxide (1.82 g, yield 100%). The reaction solution was filtered and concentrated to obtain the product, which was a colorless and transparent liquid. NMR and GC-MS examinations showed that no cyclododecanol was formed.

¹ H NMR (400 MHz, CDCl ₃ ) δ 2.88-2.68 (m, 2H), 2.14-1.77 (m, 2H), 1.50-0.99 (m, 18H).

Example 2

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-ring Dodecadiene (8.92 g, 50 mmol) and THF (50 mL) were reacted at 50 degrees under a hydrogen atmosphere of 1 atm for 28 hours to synthesize epoxydodecane (9.1 g, yield 99.5%). The reaction solution was filtered and concentrated to obtain the product, which was a colorless and transparent liquid. NMR and GC-MS examination showed that no cyclododecanol was formed, and 0.5% of unreacted raw material 9,10-epoxy-1,5-cyclododecanol remained. carbadiene.

Example 3

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-ring Dodecadiene (17.83 g, 100 mmol) and THF (50 mL) were reacted at 50 degrees under a hydrogen atmosphere of 1 atm for 48 hours to synthesize epoxydodecane. The reaction solution was filtered and concentrated to obtain the product, which was a colorless and transparent liquid. NMR and GC-MS examinations showed that no cyclododecanol was formed, and the conversion yield of epoxydodecane was >99%, and the remaining 25% was recovered. The starting material for the reaction is 9,10-epoxy-1,5-cyclododecadiene.

Example 4

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-ring Dodecadiene (17.83 g, 100 mmol) and THF (5 mL) were reacted at 50°C under 1 atm hydrogen atmosphere for 48 hours to synthesize epoxydodecane. The reaction solution was filtered and concentrated to obtain the product, which was a colorless and transparent liquid. NMR and GC-MS examinations showed that no cyclododecanol was formed, and the conversion yield of epoxydodecane was >99%, and the remaining 5% was recovered. The starting material for the reaction is 9,10-epoxy-1,5-cyclododecadiene.

Example 5

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-ring Dodecadiene (17.83 g, 100 mmol) was reacted at 50°C and 1 atm hydrogen atmosphere for 30 hours to synthesize epoxydodecane (18.2 g, 99.7%). The reaction solution was diluted with THF, filtered and concentrated to obtain the product, which was a colorless and transparent liquid. NMR and GC-MS examinations showed that no cyclododecanol was formed, and 0.25% of the unreacted raw material 9,10-epoxy-1,5- remained. Cyclododecadiene.

Example 6

Using N,N'-dimethyl-1,2-cyclohexanediamine (28.4 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 (10 mL) were reacted at 50 degrees under a hydrogen atmosphere of 1 atm for 24 hours to synthesize epoxydodecane. The reaction solution was filtered and concentrated to obtain the product, which was a colorless and transparent liquid. NMR and GC-MS examinations showed that no cyclododecanol was formed, and the conversion yield of epoxydodecane was >99%, and the remaining 15% was recovered. The starting material for the reaction is 9,10-epoxy-1,5-cyclododecadiene.

Example 7

Using tetramethylethylenediamine (23.2mg, 0.2mmol, 2mol%), 10% Pd(OH) ₂ /C (280mg, 0.2mmol, 2mol%), starting material 9,10-epoxy-1,5- Cyclododecadiene (1.78 g, 10.0 mmol) and THF (50 mL) were reacted at 50°C under 1 atm hydrogen atmosphere for 24 hours to synthesize epoxydodecane. The reaction solution was filtered and concentrated to obtain the product, which was a colorless and transparent liquid. NMR and GC-MS examinations showed that no cyclododecanol was formed, and the conversion yield of epoxydodecane was >99%, and the remaining 25% was recovered. The starting material for the reaction is 9,10-epoxy-1,5-cyclododecadiene.

Example 8

Using N,N-dimethylethylenediamine (17.6mg, 0.2mmol, 2mol%), 10% Pd(OH) ₂ /C (280mg, 0.12mmol, 2mol%), starting material 9,10-epoxy- 1,5-Cyclododecadiene (1.78 g, 10 mmol) and THF (50 mL) were reacted at 50 degrees under a hydrogen atmosphere of 1 atm for 24 hours to synthesize epoxydodecane. The reaction solution was filtered and concentrated to obtain the product, which was a colorless and transparent liquid. NMR and GC-MS examination showed that no cyclododecanol was formed, and the conversion yield of epoxydodecane was >99%, and the remaining 35% was recovered. The starting material for the reaction is 9,10-epoxy-1,5-cyclododecadiene.

Example 9

Using N,N'-dimethylethylenediamine (17.6mg, 0.2mmol, 2mol%), 10% Pd(OH) ₂ /C (280mg, 0.2mmol, 2mol%), raw material 9,10-epoxy -1,5-cyclododecadiene (1.78 g, 10 mmol) and THF (50 mL) were reacted at 50 degrees and 1 atm hydrogen atmosphere for 24 hours to synthesize epoxydodecane. The reaction solution was filtered and concentrated to obtain the product, which was a colorless and transparent liquid. NMR and GC-MS examinations showed that no cyclododecanol was formed, and the conversion yield of epoxydodecane was >99%, and the remaining 37% was recovered. The starting material for the reaction is 9,10-epoxy-1,5-cyclododecadiene.

Example 10

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-ring Dodecadiene (17.83 g, 100 mmol) was reacted at 80 degrees under a hydrogen atmosphere of 1 atm for 30 hours to synthesize epoxydodecane (18.2 g, 99.7%). The reaction solution was diluted with THF, filtered and concentrated to obtain the product, which was a colorless and transparent liquid. NMR and GC-MS examinations showed that no cyclododecanol was formed, and 0.25% of the unreacted raw material 9,10-epoxy-1,5- remained. Cyclododecadiene.

Example 11

Use the above-mentioned complex as catalyst (293mg, 0.5mmol, 1mol%), raw material 9,10-epoxy-1,5-cyclododecadiene (8.92g, 50mmol), 40mL THF, at 50 degrees, 1atm The reaction was carried out under a hydrogen atmosphere for 60 hours to synthesize epoxydodecane (9.1 g, 99%). The reaction solution was diluted with THF, filtered, and concentrated to obtain the product, which was a colorless and transparent liquid. NMR and GC-MS examinations showed that no cyclododecanol was formed, and 1% of unreacted raw materials remained 9,10-epoxy-1,5- Cyclododecadiene.

Example 12

Use the above-mentioned complex as catalyst (159mg, 0.5mmol, 5mol%), raw material 9,10-epoxy-1,5-cyclododecadiene (1.78g, 10mmol), 40mL THF, at 50 degrees, 1atm The reaction was carried out under a hydrogen atmosphere for 60 hours to synthesize epoxydodecane (1.72 g, 94%). The reaction solution was diluted with THF, filtered and concentrated to obtain the product, which was a colorless and transparent liquid. NMR and GC-MS examinations showed that no cyclododecanol was formed, and the conversion yield of epoxydodecane was >99%, and the remaining residue was recovered. 6% unreacted starting 9,10-epoxy-1,5-cyclododecadiene.

Example 13

Using the above palladium complex (190mg, 0.5mmol, 2mol%), starting material 9,10-epoxy-1,5-cyclododecadiene (4.46g, 25mmol), THF 20mL at 50 degrees, 1 atm hydrogen The reaction was carried out under the atmosphere for 40 hours to synthesize epoxydodecane (4.51 g, 99%). The reaction solution was diluted with THF, filtered, and concentrated to obtain the product, which was a colorless and transparent liquid. NMR and GC-MS examinations showed that no cyclododecanol was formed, and 1% of unreacted raw materials remained 9,10-epoxy-1,5- Cyclododecadiene.

Example 14

Use the above-mentioned complex as catalyst (132mg, 0.5mmol, 5mol%), raw material 9,10-epoxy-1,5-cyclododecadiene (1.78g, 10mmol), 40mL THF, at 50 degrees, 1atm The reaction was carried out under a hydrogen atmosphere for 60 hours to synthesize epoxydodecane (1.65 g, 90%). The reaction solution was diluted with THF, filtered and concentrated to obtain the product, which was a colorless and transparent liquid. NMR and GC-MS examinations showed that no cyclododecanol was formed, and the conversion yield of epoxydodecane was >99%, and the remaining residue was recovered. 10% unreacted starting 9,10-epoxy-1,5-cyclododecadiene.

Example 15

Use the above-mentioned complex as catalyst (183mg, 0.5mmol, 5mol%), raw material 9,10-epoxy-1,5-cyclododecadiene (1.78g, 10mmol), 40mL THF, at 50 degrees, 1atm The reaction was carried out under a hydrogen atmosphere for 60 hours to synthesize epoxydodecane (1.49 g, 81%). The reaction solution was diluted with THF, filtered and concentrated to obtain the product, which was a colorless and transparent liquid. NMR and GC-MS examinations showed that no cyclododecanol was formed, and the conversion yield of epoxydodecane was >99%, and the remaining residue was recovered. 19% unreacted starting 9,10-epoxy-1,5-cyclododecadiene.

Example 16

Use the above-mentioned complex as catalyst (213mg, 0.5mmol, 5mol%), raw material 9,10-epoxy-1,5-cyclododecadiene (1.78g, 10mmol), 40mL THF, at 50 degrees, 1atm The reaction was carried out under a hydrogen atmosphere for 60 hours to synthesize epoxydodecane (1.47 g, 80%). The reaction solution was diluted with THF, filtered and concentrated to obtain the product, which was a colorless and transparent liquid. NMR and GC-MS examinations showed that no cyclododecanol was formed, and the conversion yield of epoxydodecane was >99%, and the remaining residue was recovered. 20% unreacted starting 9,10-epoxy-1,5-cyclododecadiene.

Example 17

Under nitrogen protection, using LiI (268 mg, 2 mmol, 4 mol%), and epoxydodecane (9.11 g, 50 mmol, 1.0 equiv), heated to 165 degrees and reacted for 6 hours to synthesize cyclododecanone. Dichloromethane was diluted and filtered to remove the lithium iodide salt to obtain 9.11 g 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, CDCl ₃ ) δ 2.45-2.42 (m, 4H), 1.69-1.66 (m, 4H), 1.28 (m, 14H). ¹³ C NMR (100 MHz, CDCl ₃ ) δ 213.0, 40.3, 24.6, 24.5, 24.2, 22.5, 22.3.

Example 18

Under nitrogen protection, using LiI (134 mg, 1 mmol, 2 mol%), and epoxydodecane (9.11 g, 50 mmol, 1.0 equiv), heated to 165 degrees and reacted for 6 hours to synthesize cyclododecanone. Purified by silica gel column chromatography to obtain 8.2 g of pure product, 0.91 g of raw material was recovered at the same time, the product yield was 90%, and the product was a white solid with a melting point of 60-62°C.

Example 19

Under nitrogen protection, use LiI (134 mg, 1 mmol, 5 mol%), diglyme (10 mL) and epoxy dodecane (3.64 g, 20 mmol, 1.0 equiv), heat to 140 degrees and react for 4 hours to synthesize a ring. Dodecone. Purified by silica gel column chromatography to obtain 3.27 g of pure product with a product yield of 90%, the product is a white solid with a melting point of 59-60°C.

Example 20

Under nitrogen protection, using LiBr (87 mg, 1 mmol, 5 mol%), diglyme (10 mL) and dodecane oxide (3.64 g, 20 mmol, 1.0 equiv), heated to 140 degrees and reacted for 4 hours to synthesize a ring Dodecone. Purified by silica gel column chromatography to obtain 3.0 g of pure product, the product yield is 82%, and the product is a white solid with a melting point of 59-60°C.

Example 21

Under nitrogen protection, use NaI (150 mg, 1 mmol, 5 mol%), diglyme (10 mL) and epoxydodecane (3.64 g, 20 mmol, 1.0 equiv), heat to 140 degrees and react for 4 hours to synthesize a ring. Dodecone. Purified by silica gel column chromatography to obtain 2.84 g of pure product, the product yield is 78%, and the product is a white solid with a melting point of 59-60°C.

Example 22

Under nitrogen protection, use MgBr ₂ (184 mg, 1 mmol, 5 mol%), diglyme (10 mL) and epoxydodecane (3.64 g, 20 mmol, 1.0 equiv), heat to 140 degrees and react for 4 hours to obtain Cyclododecone. Purified by silica gel column chromatography to obtain 2.73 g of pure product, the product yield is 75%, and the product is a white solid with a melting point of 59-60°C.

Example 23

Under nitrogen protection, use MgI ₂ (278 mg, 1 mmol, 5 mol%), diglyme (10 mL) and epoxy dodecane (3.64 g, 20 mmol, 1.0 equiv), heat to 140 degrees and react for 4 hours to obtain Cyclododecone. Purified by silica gel column chromatography to obtain 3.20 g of pure product, the product yield is 88%, and the product is a white solid with a melting point of 59-60°C.

Example 24

Under nitrogen protection, use MgBr ₂ .Et ₂ O (258 mg, 1 mmol, 5 mol%), diglyme (10 mL) and dodecane oxide (3.64 g, 20 mmol, 1.0 equiv), and heat to 140 degrees to react The cyclododecanone was synthesized in 4 hours. Purified by silica gel column chromatography to obtain 3.35 g of pure product, the product yield is 92%, and the product is a white solid with a melting point of 59-60°C.

All documents mentioned herein are incorporated by reference in this application as if each document were individually incorporated by reference. In addition, it should be understood that after reading the above teaching content of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

Claims (10)

1. a preparation method of epoxy dodecane as shown in formula B, is characterized in that, it comprises the steps: in the presence of a catalyst, compound as shown in formula A carries out the hydrogenation reaction shown in the following formula to obtain as formula The compound shown in B; Described catalyst is selected from following any scheme: Scheme one: the catalyst is a palladium catalyst and an amine compound; Scheme 2; Described catalyst is the palladium complex containing amine compound; The amine compound is selected from 2,2'-bipyridine, "2,2'-bipyridine substituted by 1, 2, 3 or 4 R ^-1 " and "substituted by 1, 2, 3 or 4 R-1" One or more of R ^-2 substituted diamine compounds"; In the diamine compound substituted by 1, 2, 3 or 4 R ^-2 , R ^-2 is connected to the nitrogen atom; the diamine compound is ethylenediamine, 1,3-propanediamine, 1,4-Butanediamine or 1,2-cyclohexanediamine; each R ^-1 is independently C ₁ -C ₂₀ alkyl, halogen, phenyl, benzyloxy or phenoxy; Each R ^-2 is independently C ₁ -C ₂₀ alkyl, phenyl or benzyl;

2 . The preparation method of dodecane oxide represented by formula B according to claim 1 , wherein, in R ^-1 , the C ₁ -C ₂₀ alkyl group is a C ₁ -C ₉ alkane. 3 . Preferably, the C ₁ -C ₉ alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, Hexyl, heptyl, octyl or nonyl, for example methyl, ethyl or n-nonyl; And/or, in R ^-1 , the halogen is fluorine, chlorine, bromine or iodine; And/or, in R ^-2 , the C ₁ -C ₂₀ alkyl group is a C ₁ -C ₉ alkyl group; preferably, the C ₁ -C ₉ alkyl group is methyl, ethyl, n- propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl or nonyl, for example methyl or ethyl; And/or, the "2,2'-bipyridine substituted by 1, 2, 3 or 4 R ^-1 " is 2,2'-bipyridine substituted by 1 or 2 R ^-1 ; And/or, the palladium catalyst is a divalent palladium catalyst and/or a zerovalent palladium catalyst. 3. the preparation method of epoxy dodecane shown in formula B as claimed in claim 2, is characterized in that, in described hydrogenation reaction, each R ^-1 is identical; and/or, each R ^{-2 is} the same; and/or, each R ^-2 is independently C ₁ -C ₉ alkyl; and/or, each R ^-1 is independently C ₁ -C ₉ alkyl; And/or, the 2,2'-bipyridine substituted by 2 R ^-1 is

And/or, the divalent palladium catalyst is Pd(OAc) ₂ , PdBr ₂ , chlorine-containing divalent palladium, Pd(OH) ₂ /C, palladium trifluoroacetate, bis(acetylacetonate) palladium, pivalic acid palladium,

one or more of; And/or, the zero-valent palladium catalyst is Pd ₂ (dba) ₃ , Pd(dba) ₂ , Pd ₂ (dba) ₃ .CHCl ₃ , Pd(PPh ₃ ) ₄ , Pd(PCy ₃ ) ₂ , Pd One or more of (COD) ₂ and Pd/C. 4. the preparation method of epoxydodecane shown in formula B as claimed in claim 3, is characterized in that, described amine compound is 2,2'-bipyridine or "by 1, or 2 R ^-1 substituted 2,2'-bipyridine"; And/or, the described chlorine-containing divalent palladium is dichlorodi(tricyclohexyl) palladium, allyl palladium(II) chloride dimer, [1,3-bisdiphenylphosphorane] chlorine Palladium, 1,2-bis(diphenylphosphino)ethanedichloride palladium(II), (1,5-cyclooctadiene)dichloride palladium(II), palladium dichloride, PdCl ₂ (dppf), _PdCl2 ( _PPh3 ) ₂ , _PdCl2 (Xantphos), [PdCl( _C3H5 )] ₂ , _PdCl2 (MeCN) ₂ or _{PdCl2 (} PhCN). 5. the preparation method of epoxy dodecane shown in formula B as claimed in claim 3, is characterized in that, described amine compound is selected from 2,2'-bipyridine, "by 1, or 2 One or more of "2,2'-bipyridine substituted with 1 R ^-1 " and "diamine compound substituted with 1 or 2 R ^-2 "; each R ^-1 is C ₁ -C ₉ alkyl or phenyl; each R ^-2 is C ₁ -C ₂₀ alkyl or benzyl; preferably, the amine compound is selected from 2,2'-bipyridine, N,N'-dimethyl-1 ,2-cyclohexanediamine, tetramethylethylenediamine, N,N-dimethylethylenediamine, N,N'-dimethylethylenediamine, (R,R)-1,2-diphenyl Ethylenediamine, (S,S)-1,2-diphenylethylenediamine, (R,S)-1,2-diphenylethylenediamine, N,N-dimethyl-1,2 - cyclohexanediamine and

one or more of; more preferably, the amine compound is 2,2'-bipyridine, N,N'-dimethyl-1,2-cyclohexanediamine, tetramethylethylenediamine Amine, N,N-dimethylethylenediamine, N,N'-dimethylethylenediamine or

Also preferably, the amine compounds are 2,2'-bipyridine, N,N'-dimethyl-1,2-cyclohexanediamine, tetramethylethylenediamine, N,N-dimethylamine Ethylenediamine or N,N'-dimethylethylenediamine; And/or, described palladium complex is selected from

one or more of; And/or, the palladium catalyst is Pd(OAc) ₂ , Pd(OH) ₂ /C or chlorine-containing divalent palladium, such as Pd(OH) ₂ /C. 6. The preparation method of epoxydodecane shown in formula B as claimed in claim 1, wherein the molar ratio of the palladium catalyst to the compound shown in formula A is 0.000001～0.99 ; preferably 0.001 to 0.1, such as 0.02, 0.01 or 0.05; And/or, the molar ratio of the complex compound to the compound represented by formula A is 0.000001-0.99; preferably 0.001-0.1, such as 0.02, 0.01 or 0.05; And/or, the molar ratio of the amine compound to the palladium catalyst is (0.1-10):1, preferably (1-3):1, such as 1:1 or 2:1; And/or, described hydrogenation is carried out in the presence of solvent-free or solvent; And/or, the reaction temperature of the hydrogenation reaction is 40 to 100°C, for example, 50 to 80°C, and also for example, 50°C or 80°C; And/or, the hydrogenation reaction is carried out in the presence of hydrogen; the pressure of the hydrogen is 0.001 atm to 100 atm, preferably 0.8 atm to 10 atm, such as 1 atm; And/or, the reaction time of the hydrogenation reaction is related to the reaction scale, preferably, the reaction time of the hydrogenation reaction is 24-60h, for example, 24h, 28h, 30h, 48h or 60h. 7. the preparation method of epoxydodecane shown in formula B as claimed in claim 6, is characterized in that, when described hydrogenation is reacted in the presence of solvent, described compound shown in formula A The molar volume ratio with the solvent is 0.01～40mmol/mL; preferably 0.2～20mmol/mL; for example 1mmol/mL, 2mmol/mL, 20mmol/mL, 0.2mmol/mL, 0.25mmol/mL or 1.25mmol/mL mL; And/or, when the hydrogenation reaction is carried out in the presence of a solvent; the solvent is one or more of ether solvents, aromatic hydrocarbon solvents, amide solvents, sulfoxide solvents and water; the The ether solvent is preferably tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, diethyl ether, dimethyl ethylene glycol or 1,4-dioxane; the aromatic hydrocarbon solvent is preferably toluene; the The amide solvent is preferably N-methylpyrrolidone, N,N-dimethylformamide, 1,3-dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone or N,N- Dimethylacetamide; the sulfoxide solvent is preferably dimethyl sulfoxide; preferably, the solvent is tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, diethyl ether, dimethyl ethyl ether One or more of diether, 1,4-dioxane, and toluene, such as tetrahydrofuran. 8. a preparation method of cyclododecanone as shown in formula C, it comprises the steps: (1) According to the preparation method of the compound represented by the formula B according to any one of claims 1 to 7, the compound represented by the formula B is prepared; (2) in the presence of a metal salt, the compound shown in the formula B carries out the rearrangement reaction shown below to obtain the compound shown in the formula C;

9. the preparation method of cyclododecanone shown in formula C as claimed in claim 8, described rearrangement reaction is carried out in the presence of solvent-free or with solvent; And/or, the metal salt is a metal halide salt; And/or, the molar ratio of the metal salt to the compound represented by formula B is 0.0001-0.99; And/or, the reaction temperature of the rearrangement reaction is 100～180℃; And/or, the reaction time of the rearrangement reaction is 4-6h. 10. the preparation method of the cyclododecanone shown in formula C as claimed in claim 9, in the described rearrangement reaction, the mol ratio of described metal salt and described compound shown in formula B is 0.001～0.1, such as 0.04, 0.02 or 0.05; And/or, the metal salt is one of LiCl, LiBr, LiI, NaCl, NaBr, NaI, KCl, KBr, KI, MgCl ₂ , MgBr ₂ , MgI ₂ , MgBr ₂ OEt ₂ and MgI ₂ OEt ₂ or more; such as LiBr, LiI, NaI, LiBr, MgBr, MgI ₂ or MgBr ₂ OEt ₂ ; And/or, the reaction temperature of the rearrangement reaction is 140～165 ℃; And/or, the reaction is carried out in the presence of diglyme; preferably, the molar volume ratio of the compound shown in formula B to the diglyme is 1 to 5 mmol/L, for example 2mmol/L.