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

Preparation method of cyclododecane oxide and cyclododecanone Download PDF

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CN115124491A
CN115124491A CN202110321836.1A CN202110321836A CN115124491A CN 115124491 A CN115124491 A CN 115124491A CN 202110321836 A CN202110321836 A CN 202110321836A CN 115124491 A CN115124491 A CN 115124491A
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张新刚
闵巧桥
王树华
苏利红
叶立峰
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Shanghai Institute of Organic Chemistry of CAS
Zhejiang Juhua Technology Center Co Ltd
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Shanghai Institute of Organic Chemistry of CAS
Zhejiang Juhua Technology Center Co Ltd
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
    • C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
    • C07C45/58—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in three-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/18—Systems containing only non-condensed rings with a ring being at least seven-membered
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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

Preparation method of cyclododecane oxide and cyclododecanone
Technical Field
The invention relates to a preparation method of cyclododecane oxide and cyclododecanone.
Background
The cyclododecanone and the building blocks of the cyclododecanone derivatives are widely applied to the aspects of biomedicine, pesticide, material science and the like. However, in conventional methods of cyclododecanone synthesis, cyclododecanone or cyclododecanol is predominantly produced by selective oxidation (e.g., (a) Barton, D.H.R.; Chavasiri, W.tetrahedron 1994,50, 19-30; (b) Balavoinea, D.D.; Barton, D.H.R.; Boivin, J.; Gref, A.; Ozbalik, N.; Rivi fre, H.tetrahedron Letters,1986,27, 2849; (c) Li's et al CN 106278814A 2017-01-04). However, these methods generally have poor selectivity, low efficiency and high energy consumption, and especially when cyclododecanone is prepared by oxidation of cyclododecanol, the cyclododecanone product has similar properties to cyclododecanol as a raw material, so that the purification of the cyclododecanone as a final product has certain difficulties, which brings great challenges to the large-scale production of high-purity cyclododecanone.
Some early theoretical studies have shown that cyclododecane oxide can undergo rearrangement reactions catalyzed by metal halide salts to give highly pure cyclododecanone ((a) Zakharkin, l.i., Guseva, v.v., Kamernitskii, d.a., Tsvetkov, v.f., and likhomannenko, v.a., zh.org.khim.1990,26,1497), (b) Champalbert, j.guillois, a.julilien, j.julilen, r.r., Lai, n.t., pascal, c.and Prange, t.tetrahedron lett.1977,20,3251; (c) Wilke, g.and Borner, p.w., ger.10711960; (d. fida. fidska, m.balbolov., e, j.wo., wash, al. 73,157 and 36l). These studies provide the possibility to a certain extent for the large-scale synthesis of highly pure cyclododecanone. However, these methods still have the following two disadvantages: 1. the above documents report that reagents used for synthesizing epoxydodecane are expensive, harsh in conditions, poor in selectivity, and difficult to perform large-scale production; 2. the existing method has the defects of expensive catalyst, high dosage, high reaction temperature, large solvent dosage and the like, and is difficult to adapt to the requirement of large-scale production.
2001, US 2004181096a12, provides a platinum-catalyzed process for the preparation of cyclododecanone, which studies show that: cyclododecanol impurities present during the preparation of epoxydodecane (at levels above 2%) have a significant impact on the rate of the rearrangement reaction and the purity of the cyclododecanone produced, 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 catalyst is used; (2) the activity of catalytic hydrogenation of the platinum catalyst is low, specifically, a high reaction temperature (70-140 ℃) and a very high hydrogenation pressure (at least 50 atmospheric pressures) need to be used, and when the hydrogen pressure is reduced (5-10 atmospheric pressures), the selectivity of a reaction system is obviously reduced, and various side reactions and impurities are obviously increased. These impurities not only affect the rate of the rearrangement reaction, but also increase the difficulty of product purification. In addition, the temperature of the rearrangement reaction in this patent is up to 200 ℃, the energy consumption is high and the requirements on the equipment are high. Therefore, the method provided by the patent is not suitable for large-scale production of high-purity cyclododecanone, and the direct application of the technology to industrial production has high technical requirements and equipment and facility challenges.
Japanese scientists (Sajiki, H.; Hattori, K.; and Hirota, K.Chem.Eur.J.2000,6,2200.) studied a process for the selective catalytic hydrogenation of 9, 10-epoxy-1, 5-cyclododecadiene using palladium/carbon complexes with ethylenediamine, which produced a mixture of epoxydodecane (97%) and cyclododecanol (3%) in 93% yield. It is noted that cyclododecanol not only affects the rearrangement reaction of cyclododecane oxide to prepare high purity cyclododecanone, but also brings difficulty to the purification of cyclododecanone product. Therefore, the method is also insufficient to support the synthesis requirement of high-purity cyclododecanone, especially for large-scale industrial production.
Therefore, the method has obvious significance for exploring a new method which has cheap and easily obtained raw materials, high efficiency, simple and convenient synthesis method, cheap and easily obtained catalyst, low consumption and mild reaction condition and is suitable for large-scale production of high-purity cyclododecanone.
Disclosure of Invention
The invention aims to solve the technical problems that in the synthesis process of cyclododecanone in the prior art, the selective hydrogenation of 9, 10-epoxy-1, 5-cyclododecadiene easily generates a cyclic alcohol byproduct, the energy consumption is high, the three wastes are high and the like. The invention provides 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 II; the catalyst is a palladium complex containing amine compounds;
the amine compound is selected from 2, 2' -bipyridine, 1,2, 3 or 4R -1 Substituted 2, 2' -bipyridines "and" substituted with 1,2, 3 or 4R -2 One or more of substituted diamine compounds ";
the quilt is 1,2, 3 or 4R -2 In the substituted diamine compound, R -2 Attached to a nitrogen atom; the diamine compound is ethylenediamine, 1, 3-propanediamine, 1, 4-butanediamine or 1, 2-cyclohexanediamine;
each R is -1 Independently is C 1 ～C 20 Alkyl, halogen, phenyl, benzyloxy, or phenoxy;
each R is -2 Independently is C 1 ～C 20 Alkyl, phenyl or benzyl;
Figure BDA0002993174910000031
in the first scheme, the palladium catalyst and the amine compound are respectively added into a system; in the second scheme, the palladium complex is a complex formed by taking a palladium-containing reagent and the amine compound which are conventional in the art as raw materials.
Said hydrogenIn the reaction, preferably, R -1 In (b), the C 1 ～C 20 Alkyl is C 1 ～C 9 An alkyl group; preferably, said C 1 ～C 9 Alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl or n-nonyl, for example methyl, ethyl or n-nonyl.
In the hydrogenation, preferably, R -1 The halogen may be fluorine, chlorine, bromine or iodine.
In the hydrogenation, R -2 In (b), the C 1 ～C 20 Alkyl is C 1 ～C 9 An alkyl group; preferably, C is 1 ～C 9 Alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl or nonyl, for example methyl or ethyl.
In the hydrogenation reaction, preferably, the amine compound is 2, 2' -bipyridyl or a "substituted amine" containing 1 or 2R -1 Substituted 2, 2' -bipyridine ".
In the hydrogenation, preferably, each R is -1 Independently is C 1 ～C 9 An alkyl group.
In the hydrogenation, preferably, the "substituted by 1,2, 3 or 4R -1 Substituted 2, 2' -bipyridines "by 1 or 2R -1 Substituted 2, 2' -bipyridines.
In the hydrogenation, preferably, each R is -1 The same is true.
In the hydrogenation, preferably, each R is -2 The same is true.
In the hydrogenation, preferably, each R is -2 Independently is C 1 ～C 9 An alkyl group.
In the hydrogenation, the hydrogenation is preferably carried out by 2R -1 Substituted 2, 2' -bipyridine is
Figure BDA0002993174910000041
In the hydrogenation reaction, preferably, the amine compound is selected from 2, 2' -bipyridine, 1 or 2R -1 Substituted 2, 2' -bipyridines "and" substituted by 1 or 2R -2 One or more of substituted diamine compounds "; each R is -1 Is C 1 ～C 9 Alkyl or phenyl; each R is -2 Is C 1 ～C 20 Alkyl or benzyl; more preferably, the amine compound is selected from the group consisting of 2,2 ' -bipyridine, N ' -dimethyl-1, 2-cyclohexanediamine, tetramethylethylenediamine, N-dimethylethylenediamine, N ' -dimethylethylenediamine, (R, R) -1, 2-diphenylethylenediamine, (S, S) -1, 2-diphenylethylenediamine, (R, S) -1, 2-diphenylethylenediamine, N-dimethyl-1, 2-cyclohexanediamine and
Figure BDA0002993174910000042
one or more of; for example, the amine compound is 2,2 ' -bipyridine, N ' -dimethyl-1, 2-cyclohexanediamine, tetramethylethylenediamine, N-dimethylethylenediamine, N ' -dimethylethylenediamine or
Figure BDA0002993174910000051
Also for example, the amine compound is 2,2 ' -bipyridine, N ' -dimethyl-1, 2-cyclohexanediamine, tetramethylethylenediamine, N-dimethylethylenediamine, or N, N ' -dimethylethylenediamine.
In the hydrogenation reaction, preferably, the palladium catalyst is a divalent palladium catalyst and/or a zero-valent palladium catalyst; the divalent palladium catalyst is preferably Pd (OAc) 2 、PdBr 2 Divalent palladium (Cl), Pd (OH) 2 C, palladium trifluoroacetate, bis (acetylacetone) palladium (II), palladium pivalate,
Figure BDA0002993174910000052
Figure BDA0002993174910000053
One or more of; the chlorine-containing divalent palladium is preferably dichloro bis (tricyclohexylphosphine) palladium, allyl palladium (II) chloride dimer and [1, 3-bis diphenyl phosphorus propane]Palladium chloride, 1, 2-bis (diphenylphosphino) ethane palladium (II) dichloride, (1, 5-cyclooctadiene) palladium (II) dichloride, palladium dichloride and 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); the zero-valent 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 one or more of Pd/C; more preferably, the palladium catalyst is Pd (OAc) 2 、Pd(OH) 2 C or divalent palladium (II) chloride, e.g. Pd (OH) 2 /C。
In the hydrogenation, preferably, the palladium complex is selected from
Figure BDA0002993174910000061
Figure BDA0002993174910000062
One or more of (a).
In the hydrogenation reaction, the molar ratio of the palladium catalyst to the compound shown in the formula A is preferably 0.000001-0.99; preferably 0.001 to 0.1, for example 0.02, 0.01 or 0.05.
In the hydrogenation reaction, the molar ratio of the complex to the compound shown in the formula A is preferably 0.000001-0.99; preferably 0.001 to 0.1, for example 0.02, 0.01 or 0.05.
In the hydrogenation reaction, the molar ratio of the amine compound to the palladium catalyst is preferably (0.1-10): 1, more preferably (1-3): 1, for example, 1:1 or 2: 1.
In the hydrogenation, the hydrogenation may 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 shown in the formula A to the solvent is 0.01-40 mmol/mL; preferably 0.2-20 mmol/mL; for example, 1mmol/mL, 2mmol/mL, 20mmol/mL, 0.2mmol/mL, 0.25mmol/mL, or 1.25 mmol/mL.
In the hydrogenation reaction, when the hydrogenation reaction is carried out in the presence of a solvent, the solvent is a conventional solvent for such reactions in the field; preferably, the solvent is one or more of an ether solvent, an aromatic hydrocarbon solvent, an amide solvent, a sulfoxide solvent and water; the ether solvent is preferably tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, diethyl ether, dimethyl ethylene diether or 1, 4-dioxane; the aromatic hydrocarbon solvent is preferably toluene; the amide solvent is preferably N-methylpyrrolidone, N-dimethylformamide, 1, 3-dimethyl-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 ethylene glycol, 1, 4-dioxane and toluene, such as tetrahydrofuran.
In the hydrogenation reaction, the reaction temperature of the hydrogenation reaction is a conventional reaction temperature of the reaction in the field, and is preferably 40 to 100 ℃, for example, 50 to 80 ℃, and further for example, 50 ℃ or 80 ℃.
In the hydrogenation, preferably, the hydrogenation is carried out in the presence of hydrogen gas at a pressure of 0.001atm to 100atm, preferably 0.8atm to 10atm, for example, 1 atm.
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 hours, such as 24 hours, 28 hours, 30 hours, 48 hours or 60 hours.
The invention also provides a preparation method of cyclododecanone shown as the formula C, which comprises the following steps:
(1) preparing the compound shown in the formula B according to the preparation method of the compound shown in the formula B;
(2) in the presence of metal salt, carrying out rearrangement reaction on the compound shown as the formula B as shown in the specification to obtain a compound shown as a formula C;
Figure BDA0002993174910000071
in the rearrangement reaction, the reaction conditions of the rearrangement reaction may be conventional in such reactions in the art.
In the rearrangement reaction, the rearrangement reaction may 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 or MgCl 2 、MgBr 2 、MgI 2 、MgBr 2 OEt 2 And MgI 2 OEt 2 One or more of (a); for example LiBr, LiI, NaI, LiBr, MgBr, MgI 2 Or MgBr 2 OEt 2 。
In the rearrangement reaction, the molar ratio of the metal salt to the compound shown in the formula B is preferably 0.0001-0.99; preferably 0.001 to 0.1, for example 0.04, 0.02 or 0.05.
In the rearrangement reaction, the reaction temperature of the rearrangement reaction is the conventional reaction temperature of the reaction in the field, such as 100-180 ℃, and further such as 140-165 ℃.
In the rearrangement reaction, the reaction is carried out in the presence of diglyme. Preferably, the molar volume ratio of the compound shown in the formula B to the diglyme is 1-5 mmol/L, such as 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 4-6 h.
The above preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention without departing from the common general knowledge in the art.
The term "halogen" refers to fluorine, chlorine, bromine or iodine.
The reagents and starting materials used in the present invention are commercially available.
The positive progress effects of the invention are as follows:
the preparation method can prepare cyclododecanone by hydrogenation of 9, 10-epoxy-1, 5-cyclododecadiene under mild reaction conditions, and the two-step reaction can be carried out without solvent, thereby reducing the discharge amount of solvent. And no alcohol by-product is generated in the step of preparing the epoxy dodecane by hydrogenating the 9, 10-epoxy-1, 5-cyclododecadiene. The cyclododecanone can be efficiently prepared from the epoxy dodecane prepared by the method. The cyclododecanone product prepared by the method has wide application in the aspects of biological medicine, pesticide, material science and the like.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the invention thereto. Experimental procedures without specifying specific conditions in the following examples were selected in accordance with conventional procedures and conditions, or in accordance with commercial instructions.
Example 1
Figure BDA0002993174910000091
2, 2' -bipyridine (31.2mg,0.2mmol,2 mol%), 10% Pd (OH) was used 2 C (280.9mg,0.2mmol,2 mol%), starting materials 9, 10-epoxy-1, 5-cyclododecadiene (1.78g,10mmol) and THF (10mL) were reacted at 50 ℃ under 1atm hydrogen atmosphere for 24 hours to synthesize epoxydodecane (1.82g, 100% yield). The reaction solution is filtered and concentrated to obtain a product which is colorless and transparent liquid, and nuclear magnetic and GC-MS inspection shows that no cyclododecanol is formed.
1 H NMR(400MHz,CDCl 3 )δ2.88-2.68(m,2H),2.14-1.77(m,2H),1.50-0.99(m,18H)。
Example 2
Figure BDA0002993174910000092
2, 2' -bipyridine (156mg,1mmol,2 mol%)10% of Pd (OH) 2 C (1.40g,1mmol,2 mol%), starting material 9, 10-epoxy-1, 5-cyclododecadiene (8.92g,50mmol) and THF (50mL) were reacted at 50 ℃ under 1atm hydrogen atmosphere for 28 hours to synthesize epoxydodecane (9.1g, 99.5% yield). The reaction solution was filtered and concentrated to give a colorless transparent liquid, and nuclear magnetic and GC-MS examination showed no cyclododecanol formation, leaving 0.5% unreacted 9, 10-epoxy-1, 5-cyclododecadiene as the starting material.
Example 3
Figure BDA0002993174910000101
2, 2' -bipyridine (156mg,1mmol,1 mol%), 10% Pd (OH) was used 2 C (1.40g,1mmol,1 mol%), raw material 9, 10-epoxy-1, 5-cyclododecadiene (17.83g,100mmol) and THF (50mL) were reacted at 50 ℃ under 1atm hydrogen atmosphere for 48 hours to synthesize epoxydodecane. The reaction solution is filtered and concentrated to obtain a product which is colorless and transparent liquid, and nuclear magnetism and GC-MS inspection show that no cyclododecanol is formed, wherein the conversion yield of the cyclododecane is>99% and recovering the remaining 25% of unreacted starting material 9, 10-epoxy-1, 5-cyclododecadiene.
Example 4
Figure BDA0002993174910000102
2, 2' -bipyridine (156mg,1mmol,1 mol%), 10% Pd (OH) was used 2 C (1.40g,1mmol,1 mol%), raw material 9, 10-epoxy-1, 5-cyclododecadiene (17.83g,100mmol) and THF (5mL) were reacted at 50 ℃ under 1atm hydrogen atmosphere for 48 hours to synthesize epoxydodecane. The reaction solution is filtered and concentrated to obtain a product which is colorless and transparent liquid, and nuclear magnetism and GC-MS inspection show that no cyclododecanol is formed, wherein the conversion yield of the cyclododecane is>99% and recovering the remaining 5% of unreacted starting material 9, 10-epoxy-1, 5-cyclododecadiene.
Example 5
Figure BDA0002993174910000103
2, 2' -bipyridine (156mg,1mmol,1 mol%), 10% Pd (OH) was used 2 C (1.40g,1mmol,1 mol%), starting material 9, 10-epoxy-1, 5-cyclododecadiene (17.83g,100mmol) was reacted under a hydrogen atmosphere of 50 ℃ and 1atm for 30 hours to synthesize epoxydodecane (18.2g, 99.7%). The reaction solution was diluted with THF, filtered and concentrated to give a colorless transparent liquid, and nuclear magnetic and GC-MS examination showed no cyclododecanol formation, leaving 0.25% unreacted 9, 10-epoxy-1, 5-cyclododecadiene as the starting material.
Example 6
Figure BDA0002993174910000111
Using N, N' -dimethyl-1, 2-cyclohexanediamine (28.4mg,0.2mmol,2 mol%), 10% Pd (OH) 2 C (280mg,0.2mmol,2 mol%), starting material 9, 10-epoxy-1, 5-cyclododecadiene (1.78g,10mmol) and THF (10mL) were reacted at 50 ℃ under 1atm hydrogen atmosphere for 24 hours to synthesize epoxydodecane. The reaction solution is filtered and concentrated to obtain a product which is colorless and transparent liquid, and nuclear magnetism and GC-MS inspection show that no cyclododecanol is formed, wherein the conversion yield of the cyclododecane is>99%, and recovering the remaining 15% of the unreacted starting 9, 10-epoxy-1, 5-cyclododecadiene.
Example 7
Figure BDA0002993174910000112
Tetramethylethylenediamine (23.2mg,0.2mmol,2 mol%), 10% Pd (OH) was used 2 C (280mg,0.2mmol,2 mol%), starting material 9, 10-epoxy-1, 5-cyclododecadiene (1.78g,10.0mmol) and THF (50mL) were reacted at 50 ℃ under 1atm hydrogen atmosphere for 24h to synthesize epoxydodecane. The reaction solution is filtered and concentrated to obtain a product which is colorless and transparent liquid, and nuclear magnetism and GC-MS inspection show that no cyclododecanol is formed, wherein the conversion yield of the cyclododecane is>99%, and recovering the remaining 25% of unreacted9, 10-epoxy-1, 5-cyclododecadiene as a starting material.
Example 8
Figure BDA0002993174910000121
N, N-dimethylethylenediamine (17.6mg,0.2mmol,2 mol%), 10% Pd (OH) was used 2 C (280mg,0.12mmol,2 mol%), starting material 9, 10-epoxy-1, 5-cyclododecadiene (1.78g,10mmol) and THF (50mL) were reacted at 50 ℃ under 1atm hydrogen atmosphere for 24 hours to synthesize epoxydodecane. The reaction solution is filtered and concentrated to obtain a product which is colorless and transparent liquid, and nuclear magnetism and GC-MS inspection show that no cyclododecanol is formed, wherein the conversion yield of the cyclododecane is>99% and recovering the remaining 35% of unreacted starting material 9, 10-epoxy-1, 5-cyclododecadiene.
Example 9
Figure BDA0002993174910000122
N, N' -dimethylethylenediamine (17.6mg,0.2mmol,2 mol%), 10% Pd (OH) was used 2 C (280mg,0.2mmol,2 mol%), starting material 9, 10-epoxy-1, 5-cyclododecadiene (1.78g,10mmol) and THF (50mL) were reacted at 50 ℃ under 1atm hydrogen atmosphere for 24h to synthesize cyclododecane oxide. The reaction solution is filtered and concentrated to obtain a product which is colorless and transparent liquid, and nuclear magnetism and GC-MS inspection show that no cyclododecanol is formed, wherein the conversion yield of the cyclododecane is>99%, and the remaining 37% of the unreacted starting material, 9, 10-epoxy-1, 5-cyclododecadiene, was recovered.
Example 10
Figure BDA0002993174910000123
2, 2' -bipyridine (156mg,1mmol,1 mol%), 10% Pd (OH) was used 2 C (1.40g,1mmol,1 mol%), raw material 9, 10-epoxy-1, 5-cyclododecadiene (17.83g,100mmol) under hydrogen atmosphere of 80 deg.C and 1atm for 30 hr to synthesizeEpoxydodecane (18.2g, 99.7%) was obtained. The reaction solution was diluted with THF, filtered and concentrated to give a colorless transparent liquid, and nuclear magnetic and GC-MS examination showed no cyclododecanol formation, leaving 0.25% unreacted 9, 10-epoxy-1, 5-cyclododecadiene as the starting material.
Example 11
Figure BDA0002993174910000131
Using the above complex as a catalyst (293mg,0.5mmol,1 mol%), 9, 10-epoxy-1, 5-cyclododecadiene (8.92g,50mmol) as a starting material and 40mL of THF were reacted at 50 ℃ under 1atm hydrogen atmosphere for 60 hours to synthesize epoxydodecane (9.1g, 99%). The reaction solution is diluted by THF, filtered and concentrated to obtain a product which is colorless and transparent, and nuclear magnetic and GC-MS inspection shows that no cyclododecanol is formed, and 1% of unreacted raw material 9, 10-epoxy-1, 5-cyclododecadiene remains.
Example 12
Figure BDA0002993174910000132
Using the above complex as a catalyst (159mg,0.5mmol,5 mol%), 9, 10-epoxy-1, 5-cyclododecadiene (1.78g,10mmol) as a starting material and 40mL of THF were reacted at 50 ℃ under 1atm hydrogen atmosphere for 60 hours to synthesize epoxydodecane (1.72g, 94%). The reaction solution was diluted with THF, filtered and concentrated to give the product as a colorless transparent liquid, and nuclear magnetic resonance and GC-MS examination showed no cyclododecanol formation, with a conversion yield of cyclododecane of > 99%, and the remaining 6% of unreacted starting material, 9, 10-epoxy-1, 5-cyclododecadiene, was recovered.
Example 13
Figure BDA0002993174910000141
Using the above palladium complex (190mg,0.5mmol,2 mol%), 9, 10-epoxy-1, 5-cyclododecadiene (4.46g,25mmol) as a starting material and 20mL of THF were reacted at 50 ℃ under 1atm hydrogen atmosphere for 40 hours to synthesize epoxydodecane (4.51g, 99%). The reaction solution is diluted by THF, filtered and concentrated to obtain a product which is colorless and transparent liquid, nuclear magnetism and GC-MS inspection show that no cyclododecanol is formed, and 1 percent of unreacted raw material 9, 10-epoxy-1, 5-cyclododecadiene remains.
Example 14
Figure BDA0002993174910000142
Using the above complex as a catalyst (132mg,0.5mmol,5 mol%), 9, 10-epoxy-1, 5-cyclododecadiene (1.78g,10mmol) as a starting material and 40mL of THF were reacted under a hydrogen atmosphere at 50 ℃ and 1atm for 60 hours to synthesize epoxydodecane (1.65g, 90%). The reaction solution was diluted with THF, filtered and concentrated to give the product as a colorless transparent liquid, nuclear magnetic and GC-MS examination showed no cyclododecanol formation with a cyclododecane conversion yield of > 99%, and the remaining 10% of unreacted starting material, 9, 10-epoxy-1, 5-cyclododecadiene, was recovered.
Example 15
Figure BDA0002993174910000151
Using the above complex as a catalyst (183mg,0.5mmol,5 mol%), 9, 10-epoxy-1, 5-cyclododecadiene (1.78g,10mmol) as a starting material and 40mL of THF were reacted at 50 ℃ under 1atm hydrogen atmosphere for 60 hours to synthesize epoxydodecane (1.49g, 81%). The reaction solution was diluted with THF, filtered and concentrated to give the product as a colorless transparent liquid, nuclear magnetic and GC-MS examination showed no cyclododecanol formation with a cyclododecane conversion yield of > 99%, and the remaining 19% of unreacted starting material, 9, 10-epoxy-1, 5-cyclododecadiene, was recovered.
Example 16
Figure BDA0002993174910000152
Using the above complex as a catalyst (213mg,0.5mmol,5 mol%), 9, 10-epoxy-1, 5-cyclododecadiene (1.78g,10mmol) as a starting material and 40mL of THF were reacted at 50 ℃ under 1atm hydrogen atmosphere for 60 hours to synthesize epoxydodecane (1.47g, 80%). The reaction solution was diluted with THF, filtered and concentrated to give the product as a colorless transparent liquid, nuclear magnetic and GC-MS examination showed no cyclododecanol formation with a cyclododecane conversion yield of > 99%, and the remaining 20% of unreacted starting material, 9, 10-epoxy-1, 5-cyclododecadiene, was recovered.
Example 17
Figure BDA0002993174910000161
Cyclododecanone was synthesized using LiI (268mg,2mmol,4 mol%) and epoxydodecane (9.11g,50mmol,1.0 eq.) under nitrogen, heated to 165 ℃ for 6 hours. Lithium iodide was filtered off by dilution with dichloromethane to give 9.11g of pure product in 99.9% yield as a white solid with a melting point of 61-63 ℃. 1 H NMR(400MHz,CDCl 3 )δ2.45-2.42(m,4H),1.69-1.66(m,4H),1.28(m,14H)。 13 C NMR(100MHz,CDCl 3 )δ213.0,40.3,24.6,24.5,24.2,22.5,22.3。
Example 18
Figure BDA0002993174910000162
Cyclododecanone was synthesized using LiI (134mg,1mmol,2 mol%) and epoxydodecane (9.11g,50mmol,1.0 eq.) under nitrogen, heated to 165 ℃ for 6 hours. The product was purified by silica gel column chromatography to give 8.2g of pure product, while recovering 0.91 g of starting material, in 90% yield, as a white solid with a melting point of 60-62 ℃.
Example 19
Figure BDA0002993174910000163
Cyclododecanone was synthesized using LiI (134mg,1mmol,5 mol%), diglyme (10mL) and epoxydodecane (3.64g,20mmol,1.0 eq.) under nitrogen, heated to 140 deg.C for 4 hours. Purification by column chromatography on silica gel gave 3.27 g of pure product in 90% yield as a white solid with a melting point of 59-60 ℃.
Example 20
Figure BDA0002993174910000171
Cyclododecanone was synthesized using LiBr (87mg,1mmol,5 mol%), diglyme (10mL) and epoxydodecane (3.64g,20mmol,1.0 eq.) under nitrogen with heating to 140 deg.C for 4 hours. Purification by column chromatography on silica gel gave 3.0 g of pure product in 82% yield as a white solid with a melting point of 59-60 ℃.
Example 21
Figure BDA0002993174910000172
Cyclododecanone was synthesized using NaI (150mg,1mmol,5 mol%), diglyme (10mL) and epoxydodecane (3.64g,20mmol,1.0 equiv.) under nitrogen with heating to 140 deg.C for 4 hours. Purification by column chromatography on silica gel gives 2.84 g of pure product in 78% yield as white solid with a melting point of 59-60 ℃.
Example 22
Figure BDA0002993174910000181
Under the protection of nitrogen, MgBr is used 2 (184mg,1mmol,5 mol%), diglyme (10mL) and epoxydodecane (3.64g,20mmol,1.0 equiv.) were heated to 140 deg.C and reacted for 4 hours to synthesize cyclododecanone. Purification by column chromatography on silica gel gave 2.73 g of pure product in 75% yield as a white solid with a melting point of 59-60 ℃.
Example 23
Figure BDA0002993174910000182
Under the protection of nitrogen, MgI is used 2 (278mg,1mmol,5 mol%), diglyme (10mL) and epoxydodecane (3.64g,20mmol,1.0 equiv.), heated to 140 deg.C and reacted for 4 hours to synthesize cyclododecanone. Purification by column chromatography on silica gel gives 3.20 g of pure product in 88% yield as white solid with a melting point of 59-60 ℃.
Example 24
Figure BDA0002993174910000183
Under the protection of nitrogen, MgBr is used 2 .Et 2 O (258mg,1mmol,5 mol%), diglyme (10mL) and epoxydodecane (3.64g,20mmol,1.0 equiv.) were heated to 140 deg.C and reacted for 4 hours to synthesize cyclododecanone. Purification by column chromatography on silica gel gave 3.35 g of pure product in 92% yield as a white solid with a melting point of 59-60 ℃.
All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims (10)

1. A preparation method of epoxy dodecane shown in a formula B is characterized by comprising 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 II; the catalyst is a palladium complex containing an amine compound;
the amine compound is selected from 2,2 ' -bipyridyl, a ' N ' -substituted pyridine, 1,2, 3 or 4R -1 Substituted 2, 2' -bipyridines "and" substituted with 1,2, 3 or 4R -2 One or more of substituted diamine compounds ";
the quilt is 1,2, 3 or 4R -2 In the substituted diamine compound, R -2 Attached to a nitrogen atom; the diamine compound is ethylenediamine, 1, 3-propanediamine, 1, 4-butanediamine or 1, 2-cyclohexanediamine;
each R is -1 Independently is C 1 ～C 20 Alkyl, halogen, phenyl, benzyloxy, or phenoxy;
each R is -2 Independently is C 1 ～C 20 Alkyl, phenyl or benzyl;
Figure FDA0002993174900000011
2. process for the preparation of epoxydodecane of formula B according to claim 1, wherein R is -1 In (b), the C 1 ～C 20 Alkyl is C 1 ～C 9 An alkyl group; preferably, C is 1 ～C 9 Alkyl 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, R -1 Wherein said halogen is fluorine, chlorine, bromine or iodine;
and/or, R -2 In (b), the C 1 ～C 20 Alkyl is C 1 ～C 9 An alkyl group; preferably, C is 1 ～C 9 Alkyl 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 said "is substituted by 1,2, 3 or 4R -1 Substituted 2, 2' -bipyridines "by 1 or 2R -1 Substituted 2, 2' -bipyridine;
and/or the palladium catalyst is a divalent palladium catalyst and/or a zero-valent palladium catalyst.
3. The process according to claim 2 for the preparation of epoxydodecane of formula B, wherein in the hydrogenation reaction, each R is -1 The same;
and/or, each R -2 The same;
and/or, each R -2 Independently is C 1 ～C 9 An alkyl group;
and/or, each R -1 Independently is C 1 ～C 9 An alkyl group;
and/or said is substituted by 2R -1 Substituted 2, 2' -bipyridines as
Figure FDA0002993174900000021
And/or the divalent palladium catalyst is Pd (OAc) 2 、PdBr 2 Divalent palladium (Cl), Pd (OH) 2 C, palladium trifluoroacetate, palladium bis (acetylacetonate), palladium pivalate, palladium acetate, palladium salt, and palladium salt,
Figure FDA0002993174900000022
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(COD) 2 And Pd/C.
4. The process of claim 3, wherein the amine compound is 2, 2' -bipyridine or "quilt 1, or 2R -1 Substituted 2, 2' -bipyridine ";
and/or the chlorine-containing bivalent palladium is dichloro bis (tricyclohexyl)Palladium phosphine, allyl palladium chloride (II) dimer, [1, 3-bis diphenyl phosphopropane]Palladium chloride, 1, 2-bis (diphenylphosphino) ethane palladium (II) dichloride, (1, 5-cyclooctadiene) palladium (II) dichloride, palladium dichloride and 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)。
5. The process according to claim 3 for the preparation of epoxydodecane of formula B, wherein said amine compound is selected from 2, 2' -bipyridine, 1R or 2R -1 Substituted 2, 2' -bipyridines "and" substituted with 1 or 2R -2 One or more of substituted diamine compounds "; each R is -1 Is C 1 ～C 9 Alkyl or phenyl; each R is -2 Is C 1 ～C 20 Alkyl or benzyl; preferably, the amine compound is selected from the group consisting of 2,2 ' -bipyridine, N ' -dimethyl-1, 2-cyclohexanediamine, tetramethylethylenediamine, N-dimethylethylenediamine, N ' -dimethylethylenediamine, (R, R) -1, 2-diphenylethylenediamine, (S, S) -1, 2-diphenylethylenediamine, (R, S) -1, 2-diphenylethylenediamine, N-dimethyl-1, 2-cyclohexanediamine and
Figure FDA0002993174900000031
one or more of (a); more preferably, the amine compound is 2,2 ' -bipyridine, N ' -dimethyl-1, 2-cyclohexanediamine, tetramethylethylenediamine, N-dimethylethylenediamine, N ' -dimethylethylenediamine or
Figure FDA0002993174900000032
Preferably, the amine compound is 2,2 ' -bipyridine, N ' -dimethyl-1, 2-cyclohexanediamine, tetramethylethylenediamine, N-dimethylethylenediamine or N, N ' -dimethylethylenediamine;
and/or, the palladium complex is selected from
Figure FDA0002993174900000033
Figure FDA0002993174900000041
One or more of;
and/or, the palladium catalyst is Pd (OAc) 2 、Pd(OH) 2 /C or divalent palladium containing chlorine, e.g. Pd (OH) 2 /C。
6. The method of claim 1, wherein the molar ratio of the palladium catalyst to the compound of formula a is 0.000001 to 0.99; preferably 0.001 to 0.1, for example 0.02, 0.01 or 0.05;
and/or the molar ratio of the complex to the compound shown as the formula A is 0.000001-0.99; preferably 0.001 to 0.1, for example 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, the hydrogenation reaction is carried out in the absence of a solvent or in the presence of a solvent;
and/or the reaction temperature of the hydrogenation reaction is 40-100 ℃, such as 50-80 ℃, and further such as 50 ℃ or 80 ℃;
and/or, the hydrogenation reaction is carried out in the presence of hydrogen; the pressure of the hydrogen gas is 0.001atm to 100atm, preferably 0.8atm to 10atm, for example 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 24-60 h, such as 24h, 28h, 30h, 48h or 60 h.
7. The method according to claim 6, wherein when the hydrogenation reaction is carried out in the presence of a solvent, the molar volume ratio of the compound represented by the formula A to the solvent is 0.01 to 40 mmol/mL; preferably 0.2-20 mmol/mL; for example 1mmol/mL, 2mmol/mL, 20mmol/mL, 0.2mmol/mL, 0.25mmol/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 an ether solvent, an aromatic hydrocarbon solvent, an amide solvent, a sulfoxide solvent and water; the ether solvent is preferably tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, diethyl ether, dimethyl ethylene diether or 1, 4-dioxane; the aromatic hydrocarbon solvent is preferably toluene; the amide solvent is preferably N-methylpyrrolidone, N-dimethylformamide, 1, 3-dimethyl-3, 4,5, 6-tetrahydro-2-pyrimidone or N, N-dimethylacetamide; the sulfoxide solvent is preferably dimethyl sulfoxide; preferably, the solvent is one or more of tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, diethyl ether, dimethylethyl ether, 1, 4-dioxane and toluene, such as tetrahydrofuran.
8. A preparation method of cyclododecanone shown as a formula C comprises the following steps:
(1) preparing the compound shown as the formula B according to the preparation method of the compound shown as the formula B as claimed in any one of claims 1 to 7;
(2) in the presence of metal salt, carrying out rearrangement reaction on the compound shown in the formula B as shown in the specification to obtain a compound shown in the formula C;
Figure FDA0002993174900000051
9. the process for preparing cyclododecanone represented by the formula C as claimed in claim 8, 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 metal halide salt;
and/or the molar ratio of the metal salt to the compound shown as the 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 4-6 h.
10. The method according to claim 9, wherein the molar ratio of the metal salt to the compound represented by formula B in the rearrangement reaction is 0.001-0.1, such as 0.04, 0.02 or 0.05;
and/or the metal salt is LiCl, LiBr, LiI, NaCl, NaBr, NaI, KCl, KBr, KI, MgCl 2 、MgBr 2 、MgI 2 、MgBr 2 OEt 2 And MgI 2 OEt 2 One or more of; for example 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, in the presence of diglyme; preferably, the molar volume ratio of the compound shown in formula B to the diglyme is 1-5 mmol/L, such as 2 mmol/L.
CN202110321836.1A 2021-03-25 2021-03-25 Preparation method of cyclododecane oxide and cyclododecanone Pending CN115124491A (en)

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