CN105367517A - Preparation method of solanone and synthetic intermediate thereof - Google Patents
Preparation method of solanone and synthetic intermediate thereof Download PDFInfo
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- CN105367517A CN105367517A CN201510476119.0A CN201510476119A CN105367517A CN 105367517 A CN105367517 A CN 105367517A CN 201510476119 A CN201510476119 A CN 201510476119A CN 105367517 A CN105367517 A CN 105367517A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
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- C—CHEMISTRY; METALLURGY
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- 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
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Abstract
The invention relates to a preparation method of solanone and a synthetic intermediate thereof and provides a safe industrial method using not many steps to prepare a large amount of solanone as a flavor compound. The solution comprises using N-(3-methyl-1-yl) piperidine and 4-acryloyl morpholine for Michael addition reaction , then performing hydrolysis of acid to generate a novel aldehyde, making the aldehyde to carry out Wittig reactions, so that a novel morpholine amide compound is provided as a synthetic intermediate of the preparation method of the solanone. Then the compound reacts with a Grignard reagent, so that the solanone is prepared by means of the industrial method.
Description
Technical field
The present invention relates to solanone useful for flavor compounds etc. novel processing step and for preparing new intermediate useful for solanone.
Background technology
Solanone, as the oxygenolysis thing of the diterpene comprised in cigarette section plant and western loose alkane, is separated as the important aroma component of cigarette in nineteen sixty-five, is determined structure (non-patent literature 1) by organic synthesis.It confirms that its fragrance to cigarette, especially smoke have excellent effect for having the ketone of the carbonatoms 13 of the double bond of having carried out conjugation in molecule, proposes multiple synthetic method.
Using isovaleric aldehyde and vinyl cyanide as raw material, it is easy for utilizing witig reaction to carry out the method (non-patent literature 1) of synthesizing as laboratory scale synthetic method by the nitrile being imported with conjugated double bond.But, in the industrial production, when reacting with the Grignard reagent being converted to methyl ketone by cyano group, there is solvent and convert the difficult points such as benzene to by diethyl ether.Also proposed the trial utilizing evaporation to import conjugated double bond, but when there is dehydration reaction, conjugated double bond is moved and generates the problem of different solanone.In addition, there is the problem (patent documentation 1) of the lithium methide having used bad temper high to convert cyano group to methyl ketone.Also proposed the method (non-patent literature 2) utilizing similar method to carry out synthesizing by Ethylisovalerate.
In addition, also proposed the synthetic method based on rearrangement reaction, but existence can generate the problem (patent documentation 2) of the different solanone that conjugated double bond moves.
On the other hand, propose using natural matter and limonene as the trial of raw material.Also proposed following method: as photooxidation reaction and committed step via the method (non-patent literature 3) of acetylene intermediate; In addition, the method (patent documentation 3 and non-patent literature 4) of the keto-aldehyde synthesis solanone obtained by carrying out ozone oxidation to menthene.But it comprises protection, deprotection operation, in addition, import conjugated double bond and need hot conditions.And then, also proposed the method (patent documentation 4) of being synthesized solanone by ketone acetal menthene being carried out to ozone decomposed, reduction, acetalation obtain.But, due to the multiple operation of needs, be therefore not suitable for industrialization.
Also proposed as material choice limonene oxide compound and do not use the method for making (patent documentation 5) of the solanone intermediate of ozone oxidation.There is the advantage that can obtain natural type optical activity solanone in these methods, but needs multiple operation, is not the method for making of a large amount of solanone of industrial supply.
Not yet develop the structure that can meet unstable conjugated double bond and easily to the preparation method of both methyl ketone conversions.Like this, not yet propose to utilize less operation and the method for safety synthesizes the preparation method of the solanone important as flavor compounds in a large number.Especially, the structure that can meet unstable conjugated double bond is expected to develop and easily to the preparation method of both methyl ketone conversions.
Prior art document
Patent documentation
Patent documentation 1: United States Patent (USP) No. 4412083 specification sheets
Patent documentation 2: United States Patent (USP) No. 4433695 specification sheets
Patent documentation 3: Japanese Laid-Open Patent Publication 64-66137 publication
Patent documentation 4: Japanese Patent Publication 7-100675 publication
Patent documentation 5: Japanese Unexamined Patent Publication 2013-1695 publication
Non-patent literature
Non-patent literature 1:TheJournalofOrganicChemistry(1965), 30(9), 2918-2921
Non-patent literature 2:BulletinoftheKoreanChemicalSociety(1993), 14(5), 639-641
Non-patent literature 3:JournaloftheChemicalSociety, ChemicalCommunications(1981), 951-952
Non-patent literature 4:Synthesis, 1994(7), 692-694.
Summary of the invention
The problem that invention will solve
The object of the invention is to, to provide by less operation and the method for safety industrially prepares the method for the solanone important as flavor compounds in a large number.
For the means of dealing with problems
The present inventor etc. conduct in-depth research to solve above-mentioned problem; found that following method: by making N-(3-methyl isophthalic acid-butenyl) piperidines and 4-acryloyl morpholine generation Michael reaction; then novel aldehyde is generated by acid hydrolysis; make this aldehyde generation witig reaction and generate novel morpholino amide; and then itself and Grignard reagent are reacted; thus utilize commercial run to prepare the method for solanone in a large number, thus complete the present invention.
Novel morpholino amide compound shown in formula (1) can derive methyl ketone etc. simply under the condition keeping the conjugated double bond in molecule, and it can be described as the compound of the crucial synthetic intermediate for the preparation of the various terpenes taking solanone as representative.In addition, this compound is also still unrecorded novel cpd in document in the known scope such as the present inventor.
Therefore, the invention provides following, as that synthetic intermediate compound, its preparation method, prepared the compound of the method for solanone and the new precursor for the preparation of this intermediate by this compound.
(1) compound represented by following formula (1).
[changing 1]
。
The preparation method of the compound shown in formula (1) (2) Gen Ju (1), it comprises following operation:
Make the N-(3-methyl isophthalic acid-butenyl shown in following formula (4)) the 4-acryloyl morpholine generation Michael reaction shown in piperidines and following formula (5), then, obtained the operation of the compound shown in following formula (6) by acid hydrolysis;
Make the halo 2-methyl-2-propenyl triphenyl phosphonium shown in following formula (7) and the operation operating the compound generation witig reaction shown in formula (6) obtained like this.
[changing 2]
[changing 3]
[changing 4]
[changing 5]
(in formula, X represents halogen atom, and Ph represents phenyl).
The preparation method of the solanone (3) represented by following formula (8),
[changing 6]
It comprises and the operation that can the Grignard reagent of methyl carbonyl be become to react the morpholino amide fractional conversion of the compound shown in the formula (1) described in (1).
(4) compound represented by following formula (6).
[changing 7]
。
The effect of invention
According to the present invention, can to provide compared with method for making in the past and can be prepared the method for the solanone useful as flavor compounds in a large number by commercial run using casual labourer's sequence, and the novel synthetic intermediates effectively can preparing with solanone the various terpenes being representative can be provided.
Embodiment
Below, the present invention is described in more detail for pin.
One of embodiments of the present invention relate to shown in following formula (1), as preparation be the synthetic intermediate of the various terpenes of representative and important novel cpd with solanone.
[changing 8]
。
As this terpenes except solanone, do not limit, different solanone (5-sec.-propyl-8-the methyl-5 that can form other cigarette flavoring composition can be listed, 7-nonadiene-2-ketone), norsolandione (5-sec.-propyl-6-nonene-2, 8-diketone), somnirol (solanol) (5-sec.-propyl-8-methyl-6, 8-nonadiene-2-alcohol), 8-oxo-5-sec.-propyl-2-methyl-3-nonene-2-alcohol, 8-oxo-5-sec.-propyl-2-methyl-4-nonene-2-alcohol, 8-oxo-5-sec.-propyl-3-nonene-2-alcohol, 8-sec.-propyl-11-methyl-9, 11-12 carbon diene-5-ketone, 7-sec.-propyl-2, 10-dimethyl-8, 10-11 carbon diene-4-ketone, 7-sec.-propyl-3, 10-dimethyl-8, 10-11 carbon diene-4-ketone etc.
N-(3-methyl isophthalic acid-butenyl shown in the previously described formula (4) used as initial substance of the present invention) piperidines can utilize known method to prepare, such as shown in following reaction formula, by dripping isovaleric aldehyde to prepare using piperidines as raw material.
[changing 9]
。
For by the N-(3-methyl isophthalic acid-butenyl shown in the isovaleric aldehyde preparation formula (4) shown in the piperidines shown in formula (2) and formula (3)) piperidines and the isovaleric aldehyde used use 0.2 mole ~ 2 moles relative to 1 mole of piperidines, preferably use 0.8 ~ 1.2 mole.
N-(3-methyl isophthalic acid-the butenyl shown in previously described formula (4) is prepared for utilizing previous reaction formula) piperidines and the salt of wormwood that uses uses 0.1 ~ 0.5 mole relative to 1 mole of piperidines, preferably uses 0.2 ~ 0.4 mole, thus the yield of the compound of formula (4) can be improved.
In order to by the N-(3-methyl isophthalic acid-butenyl shown in the isovaleric aldehyde preparation formula (4) shown in the piperidines shown in formula (2) and formula (3)) piperidines, preferably, first piperidines and salt of wormwood are fed in reaction vessel, in nitrogen atmosphere, drip isovaleric aldehyde at low temperatures in reaction vessel, temperature of reaction is preferably the scope of 0 DEG C ~ 30 DEG C.
Aldehyde shown in following formula (6) is still unrecorded novel cpd in existing document; as as shown in following reaction formula; can by making the N-(3-methyl isophthalic acid-butenyl shown in following formula (4)) the 4-acryloyl morpholine generation Michael reaction shown in piperidines and following formula (5), then carry out acid hydrolysis to prepare.Therefore, the compound shown in this formula (6) is the important synthetic intermediate based on compound formula of the present invention (1) Suo Shi in addition, and it provides as a mode of the present invention.
[changing 10]
。
Because the 4-acryloyl morpholine shown in formula (5) is polymer raw material, therefore industrially can obtain at an easy rate.Such as 4-acryloyl morpholine (Tokyo HuaCheng Industry Co., Ltd's system), 4-acryloyl morpholine (Wako Pure Chemical Industries, Ltd.'s system), 4-acryloyl morpholine (Xing people Off ィ Le system & ケ ミ カ Le Inc. can be listed) etc.
By carrying out Michael reaction to the compound shown in the compound shown in formula (4) and formula (5), then carry out acid hydrolysis, thus can the compound of preparation formula (6).The Compound Phase shown in formula (5) now used preferably uses 0.5 ~ 3.0 mole for the compound 1 mole shown in formula (4), preferably uses 1.0 ~ 2.0 moles further.
Previous reaction preferably carries out heated and stirred reaction in a nitrogen atmosphere.About Heating temperature, preferably with 100 DEG C ~ 150 DEG C, preferably further to react with 120 DEG C ~ 140 DEG C, about heat-up time, can point out out 30 minutes ~ 12 hours, preferably can point out out the condition of 2 hours ~ 6 hours.
As long as in previous reaction formula, the acid that uses in the acid hydrolysis acid that can be hydrolyzed just is not particularly limited, be preferably the salt of strong acid weak base.Such as ammonium chloride, ammonium sulfate etc. can be listed.
Morpholino amide compound shown in following formula (1) is still unrecorded novel cpd in existing document, as as shown in following reaction formula, under the existence of alkali hydride, there is witig reaction by making the aldehyde shown in the halo 2-methyl-2-propenyl triphenyl phosphonium shown in following formula (7) and following formula (6) and prepare.
[changing 11]
(in formula, X represents halogen atom, and Ph represents phenyl).
Wittig reagent when carrying out the witig reaction of previously described formula and the compound shown in formula (7) can react by making triphenylphosphine and 2-methyl-2-acrylate chloride and obtain.This Wittig reagent is particularly preferably chlorination 2-methyl-2-propenyl triphenyl phosphonium, bromination 2-methyl-2-propenyl triphenyl phosphonium etc.
Use 0.5 ~ 5.0 mole by the Wittig reagent shown in the formula (7) that makes previous reaction formula use relative to 1 mole, aldehyde shown in formula (6), preferably use 1.0 ~ 3.0 moles, can witig reaction be promoted.
The alkali hydride used when carrying out the witig reaction of previously described formula can list such as sodium hydride, potassium hydride KH, hydrolith, magnesium hydride.In addition, by making this alkali hydride use 0.2 ~ 5.0 mole relative to 1 mole, aldehyde shown in formula (6), preferably use 1.0 ~ 2.0 moles, witig reaction can be promoted.
The solvent used when carrying out the witig reaction of previously described formula can list such as diethyl ether, diisopropyl ether, methyl tertiary butyl ether, cyclopentyl-methyl ether, 2-methyl-propyl methyl ether, 1, the ether series solvents such as 4-diox, tetrahydrofuran (THF), are particularly suitable for as tetrahydrofuran (THF).
Reaction times when carrying out the witig reaction of previously described formula can list 30 minutes ~ 6 hours, preferably list 2 hours ~ 4 hours, and temperature of reaction when carrying out witig reaction can list 40 DEG C ~ 90 DEG C, preferably list 55 DEG C ~ 75 DEG C.
About the compound shown in following formula (1), as shown in following reaction formula, the morpholino amide fractional conversion in formula (1) can be become the methylmagnesium halide of methyl carbonyl carry out grignard reaction by using, can the solanone shown in preparation formula (8).
[changing 12]
(in formula, X ' represents halogen atom).
The X ' of previous reaction formula represents halogen atom, can list such as chlorine, bromine, iodine etc.In addition, the consumption of the Grignard reagent shown in MeMgX ' is preferably 0.2 ~ 5.0 mole and then be more preferably 1.0 ~ 2.0 moles relative to the compound 1 mole shown in formula (1).
Utilize the solvent used during the solanone shown in grignard reaction preparation formula (8) that such as diethyl ether, diisopropyl ether, methyl tertiary butyl ether, cyclopentyl-methyl ether, 2-methyl-propyl methyl ether, 1 can be listed by the morpholino amide compound shown in previously described formula (1), the ether series solvents such as 4-diox, tetrahydrofuran (THF), are particularly suitable for as tetrahydrofuran (THF).
In order to utilize the solanone shown in grignard reaction preparation formula (8) by the morpholino amide compound shown in previously described formula (1), preferably, first the compound of formula (1) and solvent are fed in reaction vessel, in nitrogen atmosphere, in reaction vessel, drip Grignard reagent at low temperatures.In addition, temperature is now expected not make the temperature in reaction system increase, and can exemplify-20 DEG C ~ 20 DEG C.
The formula (1) utilizing previous reaction to obtain, formula (4), the compound shown in formula (6) and formula (8) can utilize common purification process, the operation of such as distillation or silica gel chromatography method and so on carrys out purifying.
By the aforementioned operation illustrated, can the solanone shown in previously described formula (8) of high-quality of preparative chemistry purity more than 90%.
Such operation and the solanone shown in previously described formula (8) obtained such as can be added directly to grain products, rice made products, cassava goods, biscuit, millet cake, bread product, dessert, dessert, chewing gum, gelatin-gum, chocolate, ice-creams, honey, syrup, yeast product, saleratus, salt and spice, mustard, edible vinegar, sauce, cigarette, processed food, through the fruits and vegetables goods of the cooking, meat and meat products, jelly, jam, fruit sauce, egg-products, milk and milk preparation, cheese, butter and butter substitute goods, cows milk substitute, soya products, food oils, medicine, beverage, alcoholic beverage, beer, refreshment drink, mineral water, nonalcoholic drink, fruit nectar, fruit juice, coffee, tea, cocoa, edible extract, plant milk extract, meat extract, food flavouring, sweetening material, dietary supplement, gelatin, medicinal and non-glue,medicinal, tablet, buccal tablet, sugar beans (De ロ ッ プ), food such as syrup or provide with the form of spices in being added into containing solanone food.
Aforementioned spices can comprise fully known food additives, such as solvent, tackiness agent, thinner, disintegrating agent, lubricant, spices additive, tinting material, preservatives, antioxidant, emulsifying agent, stablizer, spices toughener, sweeting agent etc.
In addition, also can by aforementioned spices with all applicable forms, such as liquid form, paste form or be incorporated into parcel form on carrier/particle or coated or powder type is added in food.
As the use level of the solanone shown in previously described formula (8) relative to spices, different from the purposes etc. of target fragrance, spices, usually can coordinate 0.01 ~ 20 quality % in spices, preferably coordinate 0.1 ~ 10 quality %.
Below, utilize embodiment to further illustrate the present invention.It should be noted that, the present invention is not limited to these.
[embodiment]
Reference example 1:N-(3-methyl isophthalic acid-butenyl) synthesis of piperidines (compound of previously described formula (4))
In the four neck flasks of 3L, drop into salt of wormwood (420.0g, 3.04mol, 35.3mol%), piperidines (874.0g, 10.3mol, 1.2eq.), stir in a nitrogen atmosphere with under frozen water cooling.When internal temperature reaches 10 DEG C, drip the isovaleric aldehyde (741.0g, 8.60mol) (internal temperature is less than 25 DEG C) of 2.5 hours.After dropping, with stirring at room temperature 2.5 hours, carry out thereafter filtering, dry and concentrated, obtain thick purified 1608.2g.This thick purified is carried out purifying by underpressure distillation, obtains the N-(3-methyl isophthalic acid-butenyl shown in previously described formula (4)) piperidinyl-1 170.9g(yield 88.8%).
In addition, N-(3-methyl isophthalic acid-butenyl to obtaining in above-mentioned reference example 1) piperidines carries out gas chromatographic analysis, result is as follows: chemical purity is 99.1%(analysis condition, post: TC-1701(30m × 0.53mm), Elevated Temperature Conditions: 100 DEG C ~ 260 DEG C, after keeping 2 minutes with 100 DEG C, heat up with 20.0 DEG C/min, carrier gas: nitrogen, linear velocity: 60cm/sec, retention time: 4.7 minutes).
Embodiment 1: the synthesis of aldehyde (compound of previously described formula (6))
N-(3-methyl isophthalic acid-the butenyl shown in previously described formula (4) is dropped in the four neck flasks of 2L) piperidines (333.5g, 2.18mol) and 4-acryloyl morpholine (461.8g, 3.27mol, 1.5eq.), in a nitrogen atmosphere with 130 DEG C of heated and stirred 4 hours.Thereafter, reaction solution is cooled to room temperature, to add have 20% ammonium chloride water (5000g) 18L container in add reaction solution and vinyl acetic monomer (500g).Whole night stir after, add 10% sulfuric acid (1250g) and make pH be 1 ~ 2 scope, after making water layer saturated with sodium-chlor (1400g), be separated organic layer.Thereafter, by water layer with ethyl acetate extraction (500g × 2 time).Merge organic layer, wash according to the order of 20% salt solution (500g), 15% aqueous sodium carbonate (500g), carry out thereafter drying, concentrate, obtain the thick purified yield 88.5% of thick purified 438.5g(of the aldehyde shown in previously described formula (6)).
In addition, gas chromatographic analysis is carried out to the thick purified of the aldehyde shown in the previously described formula obtained in above-described embodiment 1 (6), result is as follows: chemical purity is 95.1%(analysis condition, post: TC-1701(30m × 0.53mm), Elevated Temperature Conditions: 100 DEG C ~ 260 DEG C, keep after 2 minutes with 100 DEG C, heat up with 20.0 DEG C/min, carrier gas: nitrogen, linear velocity: 60cm/sec, retention time: 10.8 minutes).
the physical data of formula (6) aldehyde
。
Reference example 2: the synthesis of Wittig reagent (chlorination 2-methyl-2-propenyl triphenyl phosphonium)
Triphenylphosphine (1000.0g, 3.81mol), 2-methyl-2-acrylate chloride (420.0g, 4.64mol, 1.2eq.), dimethylbenzene (2390g) is dropped into, reflux 19 hours in the four neck flasks of 5L.Thereafter, reaction solution is cooled to room temperature, after carrying out filter paper filtering, with toluene (1000g) cleaning, then carries out drying with Rotary Evaporators and vacuum pump, obtain chlorination 2-methyl-2-propenyl triphenyl phosphonium 1001.7g(yield 74.5%).
Embodiment 2: the synthesis of morpholino amide compound (compound of previously described formula (1))
Wittig reagent (988.0g, 2.81mol, 1.5eq.) synthesized by reference example 2 and tetrahydrofuran (THF) (1800g, dewater with MS5) is dropped in the four neck flasks of 10L, stir in a nitrogen atmosphere, add sodium hydride (110.0g, 2.75mol, 1.5eq.) wherein fast, stir 2 hours till no longer producing hydrogen with 50 DEG C.Thereafter, reaction solution is cooled to 10 DEG C, dropping funnel is used to spend the thick purified (being assumed to be 438.5g, purity 95.1%, 1.83mmol) and tetrahydrofuran (THF) (200g) that within 20 minutes, drip the aldehyde shown in previously described formula (6) wherein, after dropping, reflux 3 hours.After reaction solution is cooled to room temperature, carry out Quench with methyl alcohol (20g), add heptane (2000g) and stir 30 minutes.Celite filtration is carried out to it, according to the order of 20% salt solution (2000g), 10% aqueous sodium carbonate (2000g), filtrate is cleaned, carry out thereafter drying, concentrate and obtain thick purified 576.9g.Wherein, use 349.0g with 130 DEG C, 10Pa carries out distillation purifying, obtains the morpholino amide compound 251.1g(2 stage yield 70.6% shown in previously described formula (1)).
In addition, gas chromatographic analysis is carried out to the morpholino amide compound shown in the previously described formula obtained in above-described embodiment 2 (1), result is as follows: chemical purity is 85.4%(analysis condition, post: TC-1701(30m × 0.53mm), Elevated Temperature Conditions: 100 DEG C ~ 260 DEG C, after keeping 2 minutes with 100 DEG C, heat up with 20.0 DEG C/min, carrier gas: nitrogen, linear velocity: 60cm/sec, retention time: 11.3 minutes).
the physical data of formula (1) morpholino amide compound
。
Embodiment 3: the synthesis of solanone (compound of previously described formula (8))
The morpholino amide compound (being assumed to be 90.00g, purity 85.4%, 290mmol) shown in previously described formula (1), tetrahydrofuran (THF) (160mL, dewater with MS5) is dropped in the four neck flasks of 1L, stir under frozen water cooling in a nitrogen atmosphere, within 30 minutes, add the tetrahydrofuran solution (174mL, 348mmol, 1.2eq.) of 2.0M methylmagnesium-chloride with 5 ~ 15 DEG C of costs wherein.After dropping, stir at the same temperature after 20 minutes, with stirring at room temperature 1 hour 40 minutes.This reaction solution is fed in the beaker adding 10% sulfuric acid (1200g) having cooling with less than 5 DEG C, makes pH be 1, stir after 15 minutes.Thereafter, reaction solution methyl tertiary butyl ether (600mL) is extracted, according to the order of 20% salt solution (200g), 5% aqueous sodium carbonate (200g), organic layer is cleaned, carry out thereafter drying, concentrate, obtain thick purified 77.40g.
Utilize underpressure distillation to carry out purifying this thick purified, obtain the solanone 37.51g(yield 56.9% shown in previously described formula (8)).
the physical data of formula (8) solanone
。
It should be noted that, pass through
1it is E body that the coupling constant of H-NMR determines Major Diastereomer.
In addition, gas chromatographic analysis is carried out to the solanone shown in the previously described formula obtained in above-described embodiment 3 (8), result is as follows: chemical purity is that 96.8%(E, Z body adds up to) (analysis condition, post: TC-1701(30m × 0.25mm), Elevated Temperature Conditions: 70 DEG C ~ 220 DEG C, heat up with 3 DEG C/min, carrier gas: nitrogen, linear velocity: 27cm/sec, retention time: Z body 21.7 minutes, E body 22.2 minutes).And then diastereomer is than determining E:Z=12:1 by gas chromatographic analysis.
Claims (4)
1. the compound represented by following formula (1),
[changing 1]
。
2. the preparation method of the compound shown in formula according to claim 1 (1), it comprises following operation:
Make the N-(3-methyl isophthalic acid-butenyl shown in following formula (4)) the 4-acryloyl morpholine generation Michael reaction shown in piperidines and following formula (5), then, obtained the operation of the compound shown in following formula (6) by acid hydrolysis;
Make the halo 2-methyl-2-propenyl triphenyl phosphonium shown in following formula (7) and the operation operating the compound generation witig reaction shown in formula (6) obtained like this,
[changing 2]
[changing 3]
[changing 4]
[changing 5]
In formula, X represents halogen atom, and Ph represents phenyl.
3. the preparation method of the solanone represented by following formula (8),
[changing 6]
It comprises and the operation that can the Grignard reagent of methyl carbonyl be become to react the morpholino amide fractional conversion of the compound shown in formula according to claim 1 (1).
4. the compound represented by following formula (6),
[changing 7]
。
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| CN111004104A (en) * | 2019-12-06 | 2020-04-14 | 云南中烟工业有限责任公司 | (Z) -type solanone, preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4412083A (en) * | 1982-03-11 | 1983-10-25 | International Flavors & Fragrances Inc. | Process for producing solanone, norsolanadione and intermediates therefor |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111004104A (en) * | 2019-12-06 | 2020-04-14 | 云南中烟工业有限责任公司 | (Z) -type solanone, preparation method and application thereof |
| CN111004105A (en) * | 2019-12-06 | 2020-04-14 | 云南中烟工业有限责任公司 | (Z) type 7-iodo-5-isopropyl-6-en-2-one compound, and preparation method and application thereof |
| WO2021068530A1 (en) * | 2019-12-06 | 2021-04-15 | 云南中烟工业有限责任公司 | Z-type solanone, preparation method therefor, and use |
| US11198665B1 (en) * | 2019-12-06 | 2021-12-14 | China Tobacco Yunnan Industrial Co., Ltd | (z)-solanone, and preparation process and use thereof |
| CN111004105B (en) * | 2019-12-06 | 2022-08-12 | 云南中烟工业有限责任公司 | (Z) -type 7-iodo-5-isopropyl-6-en-2-one compound, and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP6050291B2 (en) | 2016-12-21 |
| CN110003135A (en) | 2019-07-12 |
| JP2016037462A (en) | 2016-03-22 |
| HK1217192A1 (en) | 2016-12-30 |
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