Preparation method of cyclic ketone

Abstract

The invention discloses a preparation method of cyclic ketone. The invention provides a preparation method of a compound as shown in a formula C. The preparation method comprises the following steps: (1) in the presence of metal salt, carrying out n-th thermal rearrangement reaction on a compound as shown in a formula B to obtain the compound as shown in the formula C; after the reaction is finished, enriching metal salt; (2) adding a compound as shown in a formula B into the reaction system in the previous step, and carrying out (n + 1) th thermal rearrangement reaction to obtain a compound as shown in a formula C; after the reaction is finished, enriching metal salt; and (3) repeating the step (2) for m times. The preparation method has the advantages of high efficiency, simplicity, convenience, high catalytic efficiency, invariable yield and purity during repeated application, mild reaction conditions, less three wastes and industrial production prospect.

Description

Technical Field

[0001] This invention relates to a method for preparing cyclic ketones. Background Technology

[0002] Cyclododecone and its derivative building blocks have wide applications in biomedicine, pesticides, and materials science. However, in traditional methods of synthesizing cyclododecone, it is mainly prepared by selective oxidation of cyclododecane or cyclododecyl alcohol (e.g., (a) Barton, DHR; Chavasiri, W. Tetrahedron 1994, 50, 19–30; (b) Balavoyena, D.; Barton, DHR; Boivin, J.; Gref, A.; Ozbalik, N.; Rivière, H. Tetrahedron Letters, 1986, 27, 2849–2852; (c) Li Junping et al. CN 106278814A 2017-01-04). However, these methods are generally poor in selectivity, inefficient, and energy-intensive. In particular, when cyclododecanol is oxidized to prepare cyclododecanone, the product cyclododecanone and the raw material cyclododecanol have similar properties, making the purification of the final product cyclododecanone difficult and posing a great challenge to the large-scale production of cyclododecanone.

[0003] Some early theoretical studies have shown that epoxide dodecane can undergo a rearrangement reaction catalyzed by metal halide salts to yield high-purity cyclododecone ((a) Zakharin, LI, Guseva, VV, Kamernitskii, DA, Tsvetkov, VF, and Likhomanenko, VA, Zh. Org. Khim. 1990, 26, 1497; (b) Champalbert, J., Guillois, A., Jullien, J., Jullien, R., Lai, NT, Pascard, C., and Prange, T. Tetrahedron Lett. 1977, 20, 3251; (c) Wilke, G. and Borner, PW, Ger. 1075601 1960; (d) Filadska, M. and Balbolov, E., J. Mol. Catal. 1992, 73, 157.). These studies have, to some extent, made the large-scale synthesis of high-purity cyclododecanone possible. However, these methods still have the following shortcomings: 1. Current methods still suffer from drawbacks such as expensive catalysts, high loading, high reaction temperatures, and large solvent consumption, making it difficult to meet the requirements of large-scale production.

[0004] Therefore, it is of great significance to explore a new method for the large-scale production of high-purity cyclododecanone, which uses inexpensive and readily available raw materials, has an efficient and simple synthesis method, uses inexpensive and readily available catalysts in low quantities, and has mild reaction conditions. Summary of the Invention

[0005] The technical problem to be solved by this invention is to overcome the shortcomings of existing technologies, such as high energy consumption and high levels of waste. This invention provides a method for preparing cyclic ketones, which obtains cyclic ketones through continuous catalytic rearrangement of epoxides. The preparation method of this invention uses inexpensive chemical basic epoxides as starting materials, is highly efficient and simple, has high catalytic efficiency, maintains constant yield and purity when repeatedly used, has mild reaction conditions, and produces less waste, thus showing promise for industrial production.

[0006] The present invention solves the above-mentioned technical problems through the following technical solutions.

[0007] This invention provides a method for preparing a compound as shown in Formula C, comprising the following steps:

[0008] (1) In the presence of a metal salt, the compound shown in formula B undergoes the nth thermal rearrangement reaction to obtain the compound shown in formula C; after the reaction is completed, the metal salt is enriched.

[0009] (2) Add the compound shown in formula B to the reaction system of the previous step to carry out the (n+1)th thermal rearrangement reaction to obtain the compound shown in formula C; after the reaction is completed, the metal salt is enriched.

[0010] (3) Repeat step (2) m times;

[0011]

[0012] Among them, ring A is C8-C 20 carbon ring,

[0013] The metal salt is lithium iodide or lithium bromide; m≥1, n≥1.

[0014] In some embodiments, the C8-C 20 The carbon ring is C8-C 15 Carbon rings; for example, C8-C 15 Monocyclic carbon rings or C8-C 15 The bicyclic carbon ring; the C8-C 15 The bicyclic carbon ring can be a bridge ring or a spiral ring.

[0015] In some embodiments, compound B is Compound C is x is 1-13.

[0016] In some implementations, x is 1, 5, or 8.

[0017] In some embodiments, the compound shown in Formula B is

[0018] In some embodiments, the compound shown in Formula C is

[0019] In some embodiments, the metal salt is lithium bromide.

[0020] In some implementations, m and n are independently 2-30, preferably 2-14, for example 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14.

[0021] In some embodiments, the thermal rearrangement reaction is carried out in an inert gas atmosphere, which may be nitrogen, helium or argon; nitrogen is preferred.

[0022] In some embodiments, the thermal rearrangement reaction is carried out in the absence of a solvent.

[0023] In some embodiments, the metal salt is added only in step (1) of the preparation method, and no additional metal salt is added in other steps.

[0024] In some embodiments, in the thermal rearrangement reaction, the molar ratio of the compound shown in Formula B to the metal salt in each thermal rearrangement reaction is 1:(0.01-0.2); preferably 1:(0.01-0.1), more preferably 1:(0.04-0.073).

[0025] In some embodiments, the reaction temperature of the thermal rearrangement reaction is 100-200°C, preferably 170-180°C.

[0026] In some embodiments, the reaction time for each thermal rearrangement reaction is 2-10 hours, for example, 4 hours, 4.5 hours or 8 hours.

[0027] In some embodiments, the enrichment is carried out by ultrashort-path distillation or rectification, preferably by ultrashort-path distillation; for example, the compound shown in Formula C is collected by rapid short-path vacuum distillation to enrich the metal salt.

[0028] Without violating common sense in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0029] The reagents and raw materials used in this invention are all commercially available.

[0030] The positive and progressive effects of this invention are as follows: the preparation method of this invention is highly efficient and simple, has high catalytic efficiency, the yield and purity remain unchanged when repeatedly used, the reaction conditions are mild, and there is little waste, which has the prospect of industrial production. Detailed Implementation

[0031] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0032] Example 1

[0033]

[0034] A 250 mL reaction tube was dried in a 120 °C oven for 30 min. Anhydrous lithium iodide (535.4 mg, 4 mmol) was added in a glove box. The oil bath temperature was raised to 180 °C, and the reaction tube was placed in the oil bath for heating while simultaneously evacuating the system using an oil pump for 30 min. Subsequently, nitrogen gas was introduced into the sealed tube. Under the nitrogen atmosphere, epoxide dodecane (B1, 10 g, 54.9 mmol) was added to the sealed tube using a syringe. The oil bath temperature was maintained at 170 °C-180 °C, and the reaction was carried out for 4 h to generate cyclododecanone C1. Then, cyclododecanone C1 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enrichment (ultra-short-path distillation enrichment) of the catalyst LiI, a second batch of epoxide dodecane (B2, 10 g, 54.9 mmol) was added to the reaction flask. The oil bath temperature was maintained at 170 °C-180 °C, and the reaction was carried out for 4 h to generate cyclododecanone C2. Then, cyclododecanone C2 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enriching with LiI catalyst, a third batch of epoxy dodecane (B3, 10 g, 54.9 mmol) was added to the reaction flask. The oil bath temperature was maintained at 170℃-180℃, and the reaction was carried out for 4 h to generate cyclododecanone C3. Then, cyclododecanone C3 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enriching with LiI catalyst, a fourth batch of epoxy dodecane (B4, 10 g, 54.9 mmol) was added to the reaction flask. The oil bath temperature was maintained at 170℃-180℃, and the reaction was carried out for 4 h to generate cyclododecanone C4. Cyclododecanone C4 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >90%). The above operation was repeated 10 times to collect cyclododecanone C4. 14 (Separation yield > 98%, purity > 99%).

[0035] 1H NMR (500MHz, CDCl3) δ2.47–2.42(m,4H),1.72-1.67(m,4H),1.30–1.23(m,14H). 13 C NMR (101MHz, CDCl3) δ213.0,40.4,24.7,24.6,24.2,22.6,22.3.

[0036] Example 2

[0037]

[0038] Take a 250 mL reaction tube and dry it in an oven at 120 °C for 60 min. Add anhydrous lithium bromide (190.7 mg, 2.2 mmol, 4 mol%, (catalyst to dodecane oxide mol ratio is 4%)) in a glove box. Heat the oil bath to 180 °C and place the reaction tube in the oil bath for heating while simultaneously evacuating the vacuum using an oil pump for 30 min. Then, fill the sealed tube with nitrogen gas. Under the nitrogen atmosphere, add dodecane oxide (B1, 10 g, 54.9 mmol) to the sealed tube using a syringe. Maintain the oil bath at 178 °C-180 °C and react for 4.5 h to generate cyclododecanone C1. Then, cyclododecanone C1 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enriching with LiBr catalyst, a second batch of epoxydodecane (B2, 10 g, 54.9 mmol) was added to the reaction flask, and the reaction was carried out at 178℃-180℃ for 4.5 h to generate cyclododecanone C2. Then, cyclododecanone C2 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enriching with LiBr catalyst, a third batch of epoxydodecane (B3, 10 g, 54.9 mmol) was added to the reaction flask, and the reaction was carried out at 178℃-180℃ for 4.5 h to generate cyclododecanone C3. Then, cyclododecanone C3 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enriching with LiBr catalyst, a fourth batch of epoxydodecane (B4, 10 g, 54.9 mmol) was added to the reaction flask, and the reaction was carried out at 178℃-180℃ for 4.5 h to generate cyclododecanone C4. Then, cyclododecanone C4 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enriching with LiBr catalyst, a fifth batch of epoxydodecane (B5, 10 g, 54.9 mmol) was added to the reaction flask, and the reaction was carried out at 178℃-180℃ for 4.5 h to generate cyclododecanone C5. Then, cyclododecanone C5 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enriching the catalyst LiBr, the sixth batch of epoxide dodecane (B6, 10 g, 54.9 mmol) was added to the reaction flask, and the reaction was maintained at 178℃-180℃ in an oil bath for 4.5 h to generate cyclododecanone C6. Cyclododecanone C6 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). The above operation was repeated 8 times to collect cyclododecanone C5. 14 (Separation yield > 98%, purity > 99%).

[0039] 1 H NMR (500MHz, CDCl3) δ2.47–2.42(m,4H),1.72-1.67(m,4H),1.30–1.23(m,14H). 13C NMR (101MHz, CDCl3) δ213.0,40.4,24.7,24.6,24.2,22.6,22.3.

[0040] Example 3

[0041]

[0042] A 250 mL reaction tube was dried in a 120 °C oven for 60 min. Anhydrous lithium bromide (190.7 mg, 2.2 mmol, 4 mol% (catalyst molar ratio 4%)) was added in a glove box. The oil bath temperature was raised to 180 °C, and the reaction tube was placed in the oil bath for heating while simultaneously evacuating the system using an oil pump for 30 min. Subsequently, nitrogen gas was introduced into the sealed tube. Under the nitrogen atmosphere, epoxide octane (B'1, 7 g, 55 mmol) was added to the sealed tube using a syringe. The oil bath temperature was maintained at 180 °C, and the reaction was carried out for 8 h. Cyclooctane C'1 was then generated. Cyclooctane C'1 was then collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enriching with the LiBr catalyst, a second batch of epoxy octane (B'2, 7 g, 55 mmol) was added to the reaction flask. The reaction was maintained at 180°C in an oil bath for 8 h, resulting in the formation of cyclooctane C'2. Cyclooctane C'2 was then collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enriching with the LiBr catalyst, a third batch of epoxy octane was added to the reaction flask. (B'3, 7 g, 55 mmol) was added to the reaction flask, and the reaction was carried out at 180 °C in an oil bath for 8 h to produce cyclooctane C'3. Then, cyclooctane C'3 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enriching the catalyst LiBr, a fourth batch of epoxy octane (B'4, 7 g, 55 mmol) was added to the reaction flask, and the reaction was carried out at 180 °C in an oil bath for 8 h to produce cyclooctane C'4. Then, cyclooctane C'4 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enriching the catalyst LiBr, the fifth batch of epoxy octane (B'5, 7 g, 55 mmol) was added to the reaction flask, and the reaction was carried out at 180°C for 8 h to produce cyclooctane C'5. Then, cyclooctane C'5 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enriching the catalyst LiBr, the sixth batch of epoxy octane (B'6, 7 g, 55 mmol) was added to the reaction flask, and the reaction was carried out at 180°C for 4.5 h to produce cyclooctane C' 6， Cyclooctanone C'6 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%); the above operation was repeated 8 times to collect cyclooctanone C'6. 14 (Separation yield > 98%, purity > 99%).

[0043] 1H NMR (400MHz, CDCl3) δ2.42–2.40(m,4H),1.90-1.84(m,4H),1.40–1.35(m,2H). 13 C NMR (101MHz, CDCl3) δ218.5,42.4,27.2,25.8,24.7.

[0044] Example 4

[0045]

[0046] A 250 mL reaction tube was dried in a 120 °C oven for 60 min. Anhydrous lithium bromide (190.7 mg, 2.2 mmol, 4 mol% (catalyst molar ratio 4%)) was added in a glove box. The oil bath temperature was raised to 180 °C, and the reaction tube was placed in the oil bath for heating while simultaneously evacuating the system using an oil pump for 30 min. Subsequently, nitrogen gas was introduced into the sealed tube. Under the nitrogen atmosphere, epoxide pentadecane (B”1, 12.5 g, 55 mmol) was added to the sealed tube using a syringe. The oil bath temperature was maintained at 180 °C, and the reaction was carried out for 8 h to generate cyclopentadecanone C”1. Then, a rapid short-path reduction was performed. Cyclopentadecanone C”1 was collected by vacuum distillation (separation yield >98%, purity >99%). After enriching with the catalyst LiBr, a second batch of epoxide pentadecane (B”2, 12.5 g, 55 mmol) was added to the reaction flask. The oil bath was maintained at 180 °C, and the reaction was carried out for 8 h to produce cyclopentadecanone C”2. Then, cyclopentadecanone C”2 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enriching with the catalyst LiBr, a third batch of epoxide pentadecane (B”3, 12.5 g, 55 mmol) was added to the reaction flask. The oil bath was maintained at 180 °C, and the reaction was carried out for 8 h. h, i.e., cyclopentadecanone C”3 is generated. Then, cyclopentadecanone C”3 is collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enriching the catalyst LiBr, the fourth batch of epoxide pentadecane (B”4, 12.5 g, 55 mmol) is added to the reaction flask, and the oil bath is maintained at 180℃ for 8 h, i.e., cyclopentadecanone C”4 is generated. Then, cyclopentadecanone C”4 is collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enriching the catalyst LiBr, the fifth batch of epoxide pentadecane (B”5, 12.5 g, 55 mmol) of cyclopentadecane was added to the reaction flask, and the reaction was carried out at 180 °C for 8 h to produce cyclopentadecane C”5. Then, cyclopentadecane C”5 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). After enriching the catalyst LiBr, the sixth batch of cyclopentadecane oxide (B”6, 12.5 g, 55 mmol) was added to the reaction flask, and the reaction was carried out at 180 °C for 4.5 h to produce cyclopentadecane C”6. Cyclopentadecane C”6 was collected by rapid short-path vacuum distillation (separation yield >98%, purity >99%). This process was repeated 8 times to collect cyclopentadecane C”6. 14 (Separation yield > 98%, purity > 99%). 1 H NMR (400MHz, CDCl3) δ2.47–2.42(m,4H),1.78-1.67(m,4H),1.30–1.23(m,18H).

[0047] Comparative example:

[0048] NaCl, NaBr, KCl, KBr, MgCl 2、Inexpensive and thermally stable catalysts such as MgBr2 showed poor reaction performance. A mixed catalyst of NaI and MgCl2 could catalyze this rearrangement reaction, but repeated use yielded unsatisfactory results. Some representative new results are shown in the following equation:

[0049]

Claims

1. A process for the preparation of a compound of formula C ###0001### C characterized in that, It comprises the following steps: (1) the n-th thermal rearrangement reaction of a compound as shown in formula B in the presence of a metal salt to obtain a compound as shown in formula C; after the reaction, the metal salt is enriched; (2) the n+1-th thermal rearrangement reaction of a compound as shown in formula B is added to the reaction system of the previous step to obtain a compound as shown in formula C; after the reaction, the metal salt is enriched; (3) repeating step (2) m times; wherein ring A is a C8-C 20 carbocyclic ring; The metal salt is lithium iodide or lithium bromide; m≥1, n≥1.

2. The production method according to claim 1, wherein It meets one or more of the following conditions, (1) said C8-C 20 carbon ring is a C8-C 15 carbon ring; for example, a monocyclic C8-C 15 carbon ring or a bicyclic C8-C 15 carbon ring; said bicyclic C8-C 15 carbon ring can be a bridged or spiro ring; (2) Compound B is Compound C is x is 1-13; (3) x is 1, 5 or 8.

3. The production method according to claim 1, wherein It meets one or more of the following conditions, (1) the compound of Formula B is (2) the compound is of Formula C (3) the metal salt is lithium bromide; (4) m and n are independently 2-30; (5) the thermal rearrangement reaction is carried out in an inert gas protective atmosphere; (6) the thermal rearrangement reaction is carried out in the absence of a solvent; and (7) in the preparation method, only the metal salt is added in step (1), and no additional metal salt is added in other steps.

4. The production method according to claim 3, wherein It meets one or two of the following conditions, (1) m and n are independently 2-14; and (2) the inert gas is nitrogen, helium or argon.

5. The production method according to claim 4, wherein It meets one or two of the following conditions, (1) m and n are independently 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14; and (2) the inert gas is nitrogen.

6. The production method according to claim 1, wherein It meets one or more of the following conditions, (1) in the thermal rearrangement reaction, the molar ratio of the compound as shown in formula B to the metal salt in each thermal rearrangement reaction is 1:(0.01-0.2); (2) the reaction temperature of the thermal rearrangement reaction is 100-200℃; and (3) in the thermal rearrangement reaction, the reaction time of each thermal rearrangement reaction is 2-10h.

7. The production method according to claim 6, wherein It meets one or more of the following conditions, (1) in the thermal rearrangement reaction, the molar ratio of the compound as shown in formula B to the metal salt in each thermal rearrangement reaction is 1:(0.01-0.1); (2) the reaction temperature of the thermal rearrangement reaction is 170-180℃; and (3) in the thermal rearrangement reaction, the reaction time of each thermal rearrangement reaction is 4h, 4.5h or 8h.

8. The production method according to claim 7, wherein In the thermal rearrangement reaction, the molar ratio of the compound as shown in formula B to the metal salt in each thermal rearrangement reaction is 1:(0.04-0.073).

9. The production method according to claim 1, wherein The enrichment method is ultra-short path distillation enrichment or rectification, preferably ultra-short path distillation enrichment.

10. The production method according to claim 9, wherein The enrichment method is to collect the compound as shown in formula C by rapid short path vacuum distillation, and the metal salt is enriched.

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