CN108002992B - Preparation method of dicyclo enol ether compound - Google Patents

Preparation method of dicyclo enol ether compound Download PDF

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CN108002992B
CN108002992B CN201711226549.2A CN201711226549A CN108002992B CN 108002992 B CN108002992 B CN 108002992B CN 201711226549 A CN201711226549 A CN 201711226549A CN 108002992 B CN108002992 B CN 108002992B
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formula
reaction
production method
compound
cycloalkanone
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CN108002992A (en
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郭斌
陈来中
李建锋
张永振
黎源
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Wanhua Chemical Group Co Ltd
Wanhua Chemical Ningbo Co Ltd
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Wanhua Chemical Ningbo Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • 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
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/69—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to carbon-to-carbon double or triple bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/94—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings

Abstract

The invention relates to a preparation method of a dicyclic enol ether compound, which comprises the step of obtaining the dicyclic enol ether compound by using cycloalkanone and an enol ether compound as starting raw materials. The produced dicyclic enol ether compound may be used in synthesizing musk perfume. The method has the advantages of mild reaction conditions, simple operation and the like.

Description

Preparation method of dicyclo enol ether compound
Technical Field
The invention relates to a preparation method of a musk intermediate, in particular to a preparation method of a musk lactone intermediate dicyclic enol ether compound.
Technical Field
The musk is a rare animal spice, has strong diffusion property, mild and elegant fragrance and good fragrance enhancing and orienting effects. In addition, musk also has medicinal value, and in Chinese pharmacopoeia, musk is contained in twenty percent of Chinese patent medicines. Thus, musk is of great importance in both the fragrance industry and the pharmaceutical industry. The musk source comprises two parts of natural musk and synthetic musk. Because the main sources of natural musk are limited, musk products in the market at present mainly comprise synthetic musk. The synthesized musk compounds have irreplaceable effects in the markets of medicines and spices, and the market demand of the synthesized musk is large. The invention relates to a synthesis method of a musk compound intermediate bicycloalkenol ether.
In patent US3856815A, allyl alcohol or allyl ester compound III' is proposed as raw material to synthesize musk compound intermediate I by free radical addition
Figure BDA0001487376560000011
Wherein X is H or-CO-alkyl, with a cycloalkanone IV
Figure BDA0001487376560000012
Then acid catalyzed cyclization is carried out to generate compound I
Figure BDA0001487376560000013
After the free radical addition using the allyl ester compound, the allyl ester is hydrolyzed and then subjected to cyclization reaction to produce the compound I. The method has the advantages of low selectivity of raw materials, more byproducts, high separation difficulty and large amount of three wastes.
The patent US4268445 is improved on the basis of US3856815A, and is characterized in that III and IV are used as raw materials, azobisisobutyronitrile or peroxide is used as a free radical initiator to synthesize a compound II, and then cyclization reaction is carried out by using acid as a catalyst to generate the compound I. The method has the advantages of multiple reaction steps, harsh operation conditions and difficult control of the reaction.
By combining the advantages and disadvantages of the synthetic routes, a novel preparation method of the dicyclic enol ether compound is provided. The method has the advantages of mild reaction conditions, simple reaction operation, high selectivity, easy product separation and suitability for industrial production.
Disclosure of Invention
The invention provides a preparation method of dicyclic enol ether. The method uses the cycloalkanone and the enol ether compound as starting raw materials to obtain the dicyclo enol ether compound. The method has the advantages of mild reaction conditions, simple operation and the like.
In order to achieve the above object, the present invention employs a method of generating radical-initiated reaction of the compound (V) by light irradiation.
Specifically, the preparation method of the dicyclic enol ether comprises the following steps: the enol ether compound of the formula (III) and the cycloalkanone of the formula (IV) are subjected to photochemical reaction,
Figure BDA0001487376560000021
wherein R is1、R2、R3Is H or C1～C4Alkyl radical, R4is-C (CH)3)、
Figure BDA0001487376560000022
Or is
Figure BDA0001487376560000023
n is 3 to 12;
obtaining bicyclic enol ethers of formula (I):
Figure BDA0001487376560000024
and an alcohol or ether substituted cycloalkanone of formula (II):
Figure BDA0001487376560000025
wherein R is1、R2、R3、R4N is as defined above.
The reaction scheme is as follows:
Figure BDA0001487376560000026
wherein n is 3 to 12, R1、R2、R3Can be H or a C1-C4 alkyl group, R4Can be-C (CH)3)、
Figure BDA0001487376560000027
Or is
Figure BDA0001487376560000031
The molar ratio of the alkenyl ether compound of the formula (III) to the cycloalkanone of the formula (IV) may be from 1:2 to 20, preferably from 1:4 to 12, more preferably from 1:5 to 10.
The reaction temperature of the invention can be 70-160 ℃, and more preferably 130-150 ℃.
The reaction may be carried out in a solvent, which may be an organic solvent such as xylene or cyclohexanol.
Further, the reaction is carried out in the presence of a catalyst, preferably R5-PhS-SPh-R5(V) Compounds of the group5Is C1-C4 alkyl group or C1-C4 alkoxy group.
The catalytic amount of the catalyst is 20-40% mol, more preferably 30-35% mol of the added amount of the compound of formula (III).
The photochemical reaction light source is a mercury lamp, a xenon lamp or a metal halide lamp, and the illumination wavelength is 700-200 nm, more preferably 400-200 nm.
The reaction time of the photochemical reaction may be 2 to 10 hours, preferably 4 to 6 hours.
Further, the method further comprises separating the bicyclic enol ether compound of formula (I) from the alcohol or ether substituted cycloalkanone of formula (II) by rectification.
Further, the separation condition is a pressure of 0.5 to 5mmHg, preferably 1 to 3mmHg, and the separation temperature is 110 to 148 ℃, preferably 117 to 133 ℃.
The method has the advantages of mild reaction conditions and simple operation.
Detailed Description
The following examples are intended to illustrate the invention in detail, but are not to be construed as limiting the invention.
GC analysis method:
gas chromatography column BETA-DEX-225; temperature of the column box: 50 ℃; sample inlet temperature: 280 ℃; the split ratio is 100: 1; carrier gas flow: 3.72 mL/min; temperature rising procedure: holding at 50 deg.C for 2min, raising to 80 deg.C at 5 deg.C/min, raising to 300 deg.C at 15 deg.C/min, and holding for 15 min.
The model of the mass spectrometer is Thermo Q active Focus.
The NMR was model Bruke 400.
Example 1
174.3g (3mol) of allyl alcohol, 2734.7g (15mol) of cyclododecanone and 216.5g (0.99mol) of diphenyl disulfide were charged into a photochemical reactor, and the reaction was completed by heating to 140 ℃ and irradiating for 6 hours with a 300w medium-pressure mercury lamp. 2196.3g of cyclododecanone is separated by a 50cm rectifying column under the condition of absolute vacuum of 3mmHg, and the fraction of 120-128 ℃/1mmHg in the kettle is continuously collected to obtain 648.2g of 2- (3-hydroxypropyl) cyclododecanone, 13-oxabicyclo [10.4.0] hexadeca-1 (12) -ene (DDP), the conversion rate of the cyclododecanone is 98.4 percent, and the DDP selectivity is 98.7 percent (calculated by the cyclododecanone).
HRMS(ESI)m/z[M+Na]+:calculated for[C15H26NaO]+:245.1876.Found:245.1869。
Example 2
40.8g (0.7mol) of allyl alcohol, 640.2g (3.5mol) of cyclododecanone and 34.5g (0.14mol) of p-toluene disulfide were charged into a photochemical reactor, and the reaction was completed by heating to 130 ℃ and irradiating with a 300w medium-pressure mercury lamp for 6 hours. 514.4g of cyclododecanone is separated by a 50cm rectifying column under the condition of absolute vacuum of 1mmHg, and fractions with the temperature of 120-128 ℃/1mmHg in a kettle are continuously collected to obtain 5.2g of 2- (3-hydroxypropyl) cyclododecanone (OCP), 148.5g of 13-oxabicyclo [10.4.0] hexadeca-1 (12) -ene (DDP), the conversion rate of the cyclododecanone is 98.2 percent, and the selectivity of the DDP is 96.8 percent (calculated by the cyclododecanone).
HRMS(ESI)m/z[M+Na]+:calculated for[C15H26NaO]+:245.1876.Found:245.1867。
Example 3
60.1g (0.83mol) of 2-methylallyl alcohol, 757.2g (4.16mol) of cyclododecanone and 74.5g (0.34mol) of diphenyl disulfide were placed in a photochemical reactor, the temperature was raised to 150 ℃ and the reaction was completed by irradiation with a 1000w medium pressure mercury lamp for 6 hours. 627.4g of cyclododecanone is separated by a 50cm rectifying column under the condition of absolute vacuum of 1mmHg, and a fraction of 128-133 ℃/2mmHg in a collection kettle is obtained, thus 133.5g of 2-methyl-13-oxabicyclo [10.4.0] hexadeca-1 (12) -ene is obtained, the conversion rate is 85.5 percent, and the selectivity is 93.6 percent (calculated by cyclododecanone).
HRMS(ESI)m/z[M+Na]+:calculated for[C16H30NaO2]+:277.2138.Found:277.2135。
Example 4
80.2g (0.7mol) of allyl tert-butyl ether, 588.4g (7mol) of cyclopentanone and 50.5g (0.23mol) of diphenyl disulfide were placed in a photochemical reactor, the temperature was raised to 140 ℃ and the reaction was completed by irradiation with a 300w medium-pressure mercury lamp for 6 h. And separating 536.1g of cyclopentanone by a 50cm rectifying column under the reduced pressure of 3mmHg, collecting 119-124 ℃/3mmHg fractions in the kettle, and obtaining 122.2g (calculated as cyclopentanone) of 2- (3-tert-butoxy-1-propyl) -cyclopentanone with the conversion rate of 88.9% and the selectivity of 98.9%.
HRMS(ESI)m/z[M+Na]+:calculated for[C12H22NaO2]+:221.1512.Found:221.1506。
Example 5
58.1g (1mol) of allyl alcohol, 914.7g (5mol) of cyclododecanone and 72.4g (0.33mol) of diphenyl disulfide were charged into a photochemical reactor, and the reaction was completed by heating to 140 ℃ and irradiating with a 500w xenon lamp for 4 hours. 747.1g of cyclododecanone is separated by a 50cm rectifying column under the condition of absolute vacuum of 1mmHg, and fractions of 120-128 ℃/1mmHg in a collection kettle are continuously collected, thus 9.6g of 2- (3-hydroxypropyl) cyclododecanone (OCP), 192.4g of 13-oxabicyclo [10.4.0] hexadeca-1 (12) -ene (DDP) (calculated by cyclododecanone) are obtained, the conversion rate of the cyclododecanone is 98.4%, the selectivity of the 2- (3-hydroxypropyl) cyclododecanone (OCP) is 1.0%, and the selectivity of the 13-oxabicyclo [10.4.0] hexadeca-1 (12) -ene (DDP) is 98.6%.
HRMS(ESI)m/z[M+Na]+:calculated for[C15H26NaO]+:245.1876.Found:245.1872。

Claims (16)

1. A preparation method of dicyclic enol ether comprises the following steps: the enol ether compound of the formula (III) and the cycloalkanone of the formula (IV) are subjected to photochemical reaction,
Figure FDA0002658032540000011
wherein R is1、R2、R3Is H or C1～C4Alkyl radical, R4is-C (CH)3) Or H, n is 3-12;
obtaining bicyclic enol ethers of formula (I):
Figure FDA0002658032540000012
and an alcohol or ether substituted cycloalkanone of formula (II):
Figure FDA0002658032540000013
wherein R is1、R2、R3、R4N is as defined above;
the photochemical reaction is carried out in the presence of a catalyst which is diphenyl disulfide or R of the formula5-PhS-SPh-R5(iv) a compound of (V), wherein R5Is C1-C4 alkyl group or C1-C4 alkoxy group.
2. The process according to claim 1, wherein the molar ratio of the alkenyl ether compound of formula (III) to the cycloalkanone of formula (IV) is 1: 2-20.
3. The process according to claim 1, wherein the molar ratio of the alkenyl ether compound of formula (III) to the cycloalkanone of formula (IV) is 1:4 to 12.
4. The process according to claim 1, wherein the molar ratio of the alkenyl ether compound of formula (III) to the cycloalkanone of formula (IV) is 1:5 to 10.
5. The production method according to any one of claims 1 to 4, wherein the reaction temperature is 70 ℃ to 160 ℃.
6. The production method according to any one of claims 1 to 4, wherein the reaction temperature is 130 to 150 ℃.
7. The production method according to any one of claims 1 to 4, wherein the reaction is carried out in a solvent selected from xylene and/or cyclohexanol.
8. The preparation method according to claim 1, wherein the catalyst is used in an amount of 20 to 40 mol% based on the amount of the compound of formula (III).
9. The preparation method according to claim 1, wherein the catalyst is used in an amount of 30 to 35 mol% based on the amount of the compound of formula (III).
10. The preparation method according to any one of claims 1 to 4, wherein the photochemical reaction light source is a mercury lamp, a xenon lamp or a metal halide lamp, and the illumination wavelength is 700 to 200 nm.
11. The method according to claim 10, wherein the wavelength of light is 400 to 200 nm.
12. The production method according to any one of claims 1 to 4, wherein the reaction time of the photochemical reaction is 2 to 10 hours.
13. The production method according to any one of claims 1 to 4, wherein the reaction time of the photochemical reaction is 4 to 6 hours.
14. The production method according to any one of claims 1 to 4, wherein the method further comprises separating the bicyclic enol ether compound of formula (I) from the alcohol-or ether-substituted cycloalkanone of formula (II) by rectification.
15. The production method according to any one of claims 1 to 4, wherein the separation conditions are a pressure of 0.5 to 5mmHg and the separation temperature is 110 to 148 ℃.
16. The production method according to any one of claims 1 to 4, wherein the separation conditions are a pressure of 1 to 3mmHg and the separation temperature is 117 to 133 ℃.
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US3856815A (en) * 1971-07-21 1974-12-24 Haarmann & Reimer Gmbh Process for the production of oxa-bicyclo alkenes

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US3856815A (en) * 1971-07-21 1974-12-24 Haarmann & Reimer Gmbh Process for the production of oxa-bicyclo alkenes

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