Method for synthesizing unsaturated ketone

Abstract

The invention belongs to the field of organic synthesis, and discloses a method for synthesizing unsaturated ketone, which comprises the following steps: in the presence of a composite catalyst, catalyzing unsaturated alcohol and alkyl acetoacetate to carry out Carroll reaction, and then carrying out post-treatment to obtain the unsaturated ketone. According to the method, the novel composite catalyst is adopted to replace a traditional basic catalyst, so that the problems of equipment corrosion and incapability of mechanical application caused by the traditional basic catalyst are solved, meanwhile, the selectivity and the yield of the reaction are improved, and industrial mass production of unsaturated ketone is facilitated.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of organic synthesis, and particularly relates to a method for synthesizing unsaturated ketones through Carroll rearrangement, and more particularly to a method for synthesizing unsaturated ketones through Carroll rearrangement of unsaturated enols and acetoacetic acid alkyl esters. BACKGROUND

[0002] Unsaturated ketones (structure as shown in formula I) have wide applications, and particularly gamma, delta-unsaturated ketones are important intermediates for synthesizing vitamins, fragrances and medicines, such as 6-methyl-5-heptene-2-ketone, 6-methyl-5-octene-2-ketone, geranyl propyl ketone and farnesyl propyl ketone are important intermediates for synthesizing fragrances and vitamin E.

[0003]

[0004] There are many methods for synthesizing unsaturated ketones, and the most common method is the acetoacetic acid ester method (US2795617) of Roche, in which acetoacetic acid alkyl ester (generally acetoacetic acid ethyl ester and acetoacetic acid methyl ester) is used as a C3 source, and the acetoacetic acid alkyl ester reacts with unsaturated enols under the catalysis of isopropyl aluminum to generate unsaturated ketones through Carroll reaction. However, the catalyst isopropyl aluminum is easily deactivated by the by-product dehydroacetic acid generated in the reaction process.

[0005] The method is improved by BASF (CN1218792A), in which the solid isopropyl aluminum is replaced by liquid acetoacetic acid aluminum obtained by the reaction of tri-sec-butyl aluminum and acetoacetic acid methyl ester, which is only beneficial to continuous production, but the tri-sec-butyl aluminum is expensive and not sufficient in supply.

[0006] Therefore, it is of great significance to develop an economic, green and efficient method for synthesizing unsaturated ketones. SUMMARY

[0007] In view of the deficiencies of the prior art, the present application provides a method for synthesizing unsaturated ketones through Carroll rearrangement, which uses a new catalyst to solve the problems of expensive catalyst, easy deactivation and unsuitability for use in the prior art, and improves the reaction selectivity and yield, which is beneficial to the industrialized mass production of unsaturated ketones.

[0008] The present application provides a method for synthesizing unsaturated ketones, which comprises the following steps: performing Carroll reaction of unsaturated alcohols and acetoacetic acid alkyl esters in the presence of a composite catalyst, and obtaining the unsaturated ketones (gamma, delta-unsaturated ketones) through post-treatment after the reaction, and the reaction formula is as follows:

[0009]

[0010] R1 is C1-C6 alkyl or C2-C6 alkenyl, preferably methyl, ethyl, 4-methyl-4-pentenyl, 4-methylpentyl, 4,8-dimethyl-3,7-dinonanyl, 2,6-dimethyl-2-nonenyl or 2,6-dimethylnonyl, most preferably R1 is methyl or ethyl. 12 R1 is C1-C6 alkyl or C2-C6 alkenyl, preferably methyl, ethyl, 4-methyl-4-pentenyl, 4-methylpentyl, 4,8-dimethyl-3,7-dinonanyl, 2,6-dimethyl-2-nonenyl or 2,6-dimethylnonyl, most preferably R1 is methyl or ethyl. 12 R1 is C1-C6 alkyl or C2-C6 alkenyl, preferably methyl, ethyl, 4-methyl-4-pentenyl, 4-methylpentyl, 4,8-dimethyl-3,7-dinonanyl, 2,6-dimethyl-2-nonenyl or 2,6-dimethylnonyl, most preferably R1 is methyl or ethyl.

[0011] R2 is C1-C4 alkyl, preferably R2 is methyl.

[0012] R3 is C1-C4 alkyl, preferably R3 is methyl or ethyl.

[0013] The composite catalyst comprises an active component, a carrier, a modifier;

[0014] The active component is composed of a first active component and a second active component.

[0015] The first active component is one or more of palladium (Pd), ruthenium (Ru), platinum (Pt) from chlorides, nitrates, sulfates and hydrates containing palladium, ruthenium, platinum elements.

[0016] The second active component is one or more of zinc (Zn), copper (Cu), iron (Fe) from chlorides, nitrates, sulfates, acetates and hydrates containing zinc, copper, iron elements.

[0017] The carrier is a large-pore molecular sieve selected from one or more of NUD-1, ITQ-44, ITQ-51, ITQ-37, SSZ-53; preferably one or both of ITQ-51 and SSZ-53.

[0018] The modifier is one or more of γ-aminopropyl triethoxysilane (KH550), γ-glycidyl ether propyl trimethoxysilane (KH560), γ-methacryloyloxy propyl trimethoxysilane (KH570), vinyl triethoxysilane (A151), vinyl trimethoxysilane (A171).

[0019] The preferred unsaturated alcohols are one or more of 2-methyl-3-buten-2-ol, 3-methyl-1-penten-3-ol, 3,7-dimethyl-1,6-octadien-3-ol (linalool), 3,7-dimethyl-1-octen-3-ol (dihydrolinalool), 3,7,11-trimethyl-1,6,10-dodecatrien-3-ol (nerolidol). The corresponding unsaturated ketones are methyl heptenone, ethyl heptenone, geranyl acetone, citronellyl acetone, farnesyl acetone.

[0020] The molar ratio of the unsaturated alcohol and the acetoacetic acid alkyl ester is 1:1.0-2.0, preferably 1:1.0-1.2.

[0021] The mass ratio of the composite catalyst and the unsaturated alcohol is 0.01-0.09:1, preferably 0.03-0.07:1.

[0022] The reaction temperature is 100-180℃, preferably 120-160℃; the reaction time is 2-6 hours, preferably 2-4 hours.

[0023] The composite catalyst is prepared by the following method:

[0024] (1) in a solvent, adding a carrier and a modifier, heating and stirring to modify, obtaining a solution of the modified carrier;

[0025] (2) adding a salt of a first active component and a salt of a second active component to the solution of the modified carrier in step (1), stirring to adsorb, filtering and drying to obtain the catalyst.

[0026] In step (1), the solvent is preferably deionized water, which can disperse the modifier.

[0027] In step (1), the mass ratio of the modifier and the carrier is 4-12:1.0, preferably 6-10:1.0.

[0028] In step (1), the temperature is 80-160℃, preferably 100-120℃; the time is 2-6 hours, preferably 4-6.

[0029] In step (2), the salt of the first active component is selected from chlorides, nitrates, sulfates and hydrates containing palladium, ruthenium and platinum elements.

[0030] The salt of the second active component is selected from chlorides, nitrates, sulfates, acetates and hydrates containing zinc, copper and iron elements.

[0031] The mass ratio of the first active component and the second active component is 1:1-6, preferably 1:2-4.

[0032] As a preferred, in step (2), the salt of the first active component is Pd(NO3)2, RuCl3•3H2O or PtCl4.

[0033] The salt of the second active component is Fe(NO3)3·9H2O, CuSO4·5H2O, FeCl3·6H2O or Zn(OAc)2·2H2O.

[0034] In step (2), the mass ratio of the first active component to the carrier is 0.5%-2.0%:1, preferably 0.5%-1.5%:1.

[0035] In step (2), the temperature is 40-60 DEG C, and the time is 2-6 hours.

[0036] Compared with the prior art, the present application has the following advantages:

[0037] The present application provides a method for preparing unsaturated ketone by catalyzing Carroll rearrangement reaction of unsaturated enol, which solves the problems of equipment corrosion and unsuitable application caused by traditional alkaline catalyst by using new catalyst instead of traditional alkaline catalyst, improves the selectivity and yield of reaction, and is beneficial to industrialized mass production of unsaturated ketone.

[0038] The catalyst of the present application uses superlarge molecular sieve modified by silane substance as carrier, the superlarge molecular sieve has low framework density and large pore size, and after being modified by silane, the hydrophilicity is increased, the reaction substrate is combined on the surface of the catalyst through hydrogen bond, the accuracy and efficiency of the active component catalysis are improved, the selectivity and efficiency of the reaction are improved, and the production energy consumption of unreacted raw material recovery and post-reaction treatment is reduced. BRIEF DESCRIPTION OF DRAWINGS

[0039] Figure 1 The mass spectrum of the product obtained in application example 1 is shown in the figure. DETAILED DESCRIPTION

[0040] Unless otherwise defined, the technical terms used in the following examples have the same meanings as generally understood by those skilled in the art to which the present application belongs. The test reagents used in the following examples are all conventional biochemical reagents unless otherwise specified; and the experimental methods are all conventional methods unless otherwise specified.

[0041] The calculation of the yield in table 3 and table 4 in the specification is as follows:

[0042] Yield = actual yield / theoretical yield * 100%

[0043] Catalyst preparation example 1

[0044] In 100ml deionized water, 80.0g of gamma-aminopropyl triethoxysilane was added, stirred and dispersed uniformly, then 10.0g of SSZ-53 carrier was added, stirred, heated to 120 DEG C, heated and stirred for 2 hours, then cooled to 40 DEG C, and then Pd(NO3)2 (0.217g) and Fe(NO3)3·9H2O (4.34g) were added in sequence, and stirred for 4 hours, then cooled to room temperature, filtered, and the obtained filter cake was dried to constant weight to obtain catalyst 1.

[0045] Catalyst preparation examples 2~3

[0046] The catalyst preparation examples 2~3 respectively provide a preparation method of a composite catalyst, which only differs from example 1 in that the Pd(NO3)2 metal salt in example 1 is replaced by RuCl3·3H2O (0.259g), PtCl4 (0.173g) respectively, and the rest is the same as example 1, to obtain catalysts 2~3 respectively.

[0047] Catalyst preparation examples 4~6

[0048] The catalyst preparation examples 4~6 respectively provide a preparation method of a composite catalyst, which only differs from example 1 in that the Fe(NO3)3·9H2O (4.34g) metal salt in example 1 is replaced by CuSO4·5H2O (2.36g), FeCl3·6H2O (2.90g), Zn(OAc)2·2H2O (2.01g) respectively, and the rest is the same as example 1, to obtain catalysts 4~6 respectively.

[0049] Catalyst preparation examples 7~12

[0050] The catalyst preparation examples 7~12 respectively provide a preparation method of a composite catalyst, which differs from example 1 in that the loading amount of the Pd(NO3)2 metal salt and the Fe(NO3)3·9H2O metal salt in example 1 is changed, and the rest is the same as example 1, as shown in Table 1, to obtain catalysts 7~12 respectively.

[0051] Table 1

[0052]

[0053] Catalyst preparation examples 13~15

[0054] The catalyst preparation examples 13~15 respectively provide a preparation method of a composite catalyst, which differs from example 1 in that the mass ratio of the carrier and the modifier in example 1 is changed from 1:8 to 1:4, 1:10, 1:12, and the corresponding modifier dosage is 40g, 100g, 120g respectively, and the rest is the same as example 1, to obtain catalysts 13~15 respectively.

[0055] Catalyst preparation examples 16~19

[0056] The catalyst preparation examples 16~19 respectively provide a preparation method of a composite catalyst, which differs from example 1 in that the carrier SSZ-53 in example 1 is replaced by NUD-1, ITQ-44, ITQ-51, ITQ-37 respectively, and the mass of the carrier remains unchanged, and the rest is the same as example 1, to obtain catalysts 16~19 respectively.

[0057] Catalyst preparation examples 20~23

[0058] The catalyst preparation examples 20~23 respectively provide a preparation method of a composite catalyst, which is different from example 1 in that the modifier γ-aminopropyl triethoxysilane in example 1 is replaced by γ-glycidoxypropyltrimethoxysilane, γ-methacryloyloxypropyltrimethoxysilane, vinyltriethoxysilane, and vinyltrimethoxysilane in turn, while the amount of the modifier is kept unchanged, and other conditions are the same as in example 1, to obtain catalysts 20~23 respectively.

[0059] Catalyst preparation examples 24~31

[0060] The catalyst preparation examples 24~31 respectively provide a preparation method of a composite catalyst, which is different from example 1 only in that the temperature and time for modifying the carrier are adjusted, and the temperature and time for adsorbing the modified carrier are adjusted, as shown in Table 2, to obtain catalysts 24~31 respectively.

[0061] Table 2

[0062]

[0063] Comparative example 1

[0064] In 100 ml of deionized water, 80.0 g of γ-aminopropyl triethoxysilane was added and stirred to disperse uniformly, then 10.0 g of Al2O3 carrier was added and stirred, and the temperature was raised to 120℃. After stirring for 2 hours, the temperature was lowered to 40℃, and Pd(NO3)2 (0.217 g) and Fe(NO3)3·9H2O (4.34 g) were added in turn. After stirring for 4 hours, the temperature was lowered to room temperature, and the filter cake was obtained by filtration and dried to constant weight to obtain the catalyst of comparative example 1.

[0065] Comparative example 2

[0066] In 100 ml of deionized water, 10.0 g of SSZ-53 carrier was added and stirred, and the temperature was raised to 120℃. After stirring for 2 hours, the temperature was lowered to 40℃, and Pd(NO3)2 (0.217 g) and Fe(NO3)3·9H2O (4.34 g) were added in turn. After stirring for 4 hours, the temperature was lowered to room temperature, and the filter cake was obtained by filtration and dried to constant weight to obtain the catalyst of comparative example 2.

[0067] Application example 1

[0068] Into a reaction vessel with distillation device, under nitrogen protection, 3-methyl-1-penten-3-ol (100 g, 0.9984 mol) and 5.0 g of catalyst 1 (catalyst concentration of 5.0%) were added, and stirred to warm up. When the temperature of the system rose to 100°C, ethyl acetoacetate (155.92 g, 1.198 mol) was added dropwise, and the speed was controlled to drop within 3 hours. After the dropwise addition was completed, the temperature of the system was raised to 140°C, and the reaction was kept for 4 hours. After the reaction was completed, vacuum distillation was carried out to obtain ethyl heptenone product 137.48 g, with a yield of 98.20%, and a GC detection purity of 99.38%. The GC purity was calculated based on the total amount of cis-ethyl heptenone and trans-ethyl heptenone, and the following was the same; Figure 1 The mass spectrum of the obtained product is shown in Figure 1.

[0069] The same method was applied for 9 more times, and the product quality and yield are shown in Table 3.

[0070] Table 3

[0071]

[0072] Application Example 2

[0073] In application example 1, ethyl acetoacetate was replaced by methyl acetoacetate (139.12 g, 1.198 mol), and the other conditions were the same as in application example 1. The results are shown in Table 4.

[0074] Application Examples 3-6

[0075] The difference between application examples 3-6 and application example 1 is only that the catalyst concentration is changed to 1.0%, 3.0%, 7.0%, and 9.0% respectively, and the corresponding catalyst amount is 1.0 g, 3.0 g, 7.0 g, and 9.0 g respectively. The other conditions are the same as in application example 1. The results are shown in Table 4.

[0076] Application Examples 7-10

[0077] The difference between application examples 7-10 and application example 1 is only that the molar ratio of 3-methyl-1-penten-3-ol to ethyl acetoacetate is changed to 1:1.0, 1:1.6, 1:1.8, and 1:2.0 respectively, and the corresponding amount of ethyl acetoacetate is 129.93 g (0.998 mol), 207.89 g (1.597 mol), 233.88 g (1.797 mol), and 259.86 g (1.997 mol) respectively. The other conditions are the same as in application example 1. The results are shown in Table 4.

[0078] Application Examples 11-16

[0079] The application examples 11-16 and the application example 1 only differ in changing the reaction temperature and the reaction time, and the others are the same as the application example 1. The temperatures of the application example 11, the application example 12, the application example 13 and the application example 14 are 100 ℃, 120 ℃, 160 ℃ and 180 ℃ respectively, and the others are the same as the application example 1. The reaction times of the application example 15 and the application example 16 are 2 hours and 6 hours respectively, and the others are the same as the application example 1. The results are shown in Table 4.

[0080] Application examples 17-46

[0081] The application examples 17-46 respectively provide a composite phase catalyst, which respectively uses the composite phase catalysts provided in the catalyst examples 2-31 above and is used in the reaction of synthesizing unsaturated ketone from unsaturated enol through Carroll rearrangement, and the others are the same as the application example 1. The results are shown in Table 4.

[0082] Application comparative examples 1-2

[0083] The application comparative examples 1-2 respectively provide an application of a composite catalyst, which only differs from the application example 1 in that the composite catalysts respectively use the composite catalysts provided in the comparative examples 1-2 above, and the others are the same as the application example 1. The results are shown in Table 4.

[0084] Table 4

[0085]

[0086]

[0087] The applicant declares that the above description is only the specific implementation of the present application, but the protection scope of the present application is not limited to this. It should be understood by those skilled in the art that any changes or replacements within the technical scope disclosed by the present application can be easily thought out by those skilled in the art, and all of them fall within the protection scope and the disclosure scope of the present application.

Claims

1. A method of synthesizing an unsaturated ketone, characterized by, The method comprises the following steps: performing Carroll reaction on unsaturated alcohol and acetyl acetic acid alkyl ester in the presence of a composite catalyst, and obtaining the unsaturated ketone after post-treatment. The reaction formula is as follows: ； wherein R1is C1-C6alkyl or C2-C6alkenyl, said C2-C6alkenyl containing one or two double bonds; 12 wherein R1is C1-C6alkyl or C2-C6alkenyl, said C2-C6alkenyl containing one or two double bonds; 12 wherein R1is C1-C6alkyl or C2-C6alkenyl, said C2-C R2 is C1-C4 alkyl; R3 is C1-C4 alkyl; The composite catalyst comprises a carrier modified by a modifier and an active component loaded on the modified carrier; The active component is composed of a first active component and a second active component; The first active component is one or more of palladium, ruthenium and platinum; The second active component is one or more of zinc, copper and iron; the carrier is a large-pore molecular sieve; The modifier is an alkoxyl-substituted silane.

2. The method of synthesizing unsaturated ketones according to claim 1, wherein, The carrier is selected from one or more of NUD-1, ITQ-44, ITQ-51, ITQ-37 and SSZ-53.

3. The method of synthesizing unsaturated ketones according to claim 1, wherein, The modifier is one or more of γ-aminopropyl triethoxysilane, γ-glycidyl ether propyl trimethoxysilane, γ-methacryloyloxy propyl trimethoxysilane, vinyl triethoxysilane and vinyl trimethoxysilane.

4. The method of synthesizing unsaturated ketones according to claim 1, wherein, The composite catalyst is prepared by the following method: (1) adding the carrier and the modifier in a solvent, stirring and modifying at a high temperature to obtain a solution of the modified carrier; (2) adding a salt of the first active component and a salt of the second active component into the solution of the modified carrier in step (1), stirring to adsorb, filtering and drying to obtain the catalyst.

5. The method of synthesizing unsaturated ketones according to claim 4, wherein, In step (1), the solvent is water, alcohol or ether solvent; In step (1), the mass ratio of the modifier to the carrier is 4-12:1.0; In step (1), the modification temperature is 80-160 ℃, and the modification time is 2-6 hours.

6. The method of synthesizing unsaturated ketones according to claim 4, wherein, In step (2), the salt of the first active component is a chloride salt, nitrate salt, sulfate salt containing palladium, ruthenium and platinum elements and hydrates thereof; The salt of the second active component is a chloride salt, nitrate salt, sulfate salt and acetate salt containing zinc, copper and iron elements and hydrates thereof; The mass ratio of the first active component to the second active component is 1:1-6, and the mass ratio of the first active component to the carrier is 0.5%-2.0%:1; The adsorption temperature is 40-60 ℃, and the adsorption time is 2-6 hours.

7. The method of synthesizing unsaturated ketones according to claim 6, wherein, In step (2), the salt of the first active component is Pd(NO3)2, RuCl3·3H2O or PtCl4; The salt of the second active component is Fe(NO3)3·9H2O, CuSO4·5H2O, FeCl3·6H2O or Zn(OAc)2·2H2O.

8. The method of synthesizing unsaturated ketones according to any one of claims 1 to 7, characterized in that, The unsaturated alcohol is one or more of 2-methyl-3-buten-2-ol, 3-methyl-1-penten-3-ol, 3,7-dimethyl-1,6-octadien-3-ol, 3,7-dimethyl-1-octen-3-ol and 3,7,11-trimethyl-1,6,10-dodecatrien-3-ol; The acetyl acetic acid alkyl ester is acetyl acetic acid methyl ester or acetyl acetic acid ethyl ester.

9. The method of synthesizing unsaturated ketones according to any one of claims 1 to 7, wherein, The molar ratio of the unsaturated alcohol to the acetyl acetic acid alkyl ester is 1:1.0-2.

0. The mass ratio of the composite catalyst to the unsaturated alcohol is 0.01-0.09:

1.

10. The method of synthesizing unsaturated ketones according to any one of claims 1 to 7, wherein, The temperature of the Carroll reaction is 100-180 DEG C, and the reaction time is 2-6 hours.

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