CN107011136A - A kind of synthetic method of anti-4 decenal - Google Patents
A kind of synthetic method of anti-4 decenal Download PDFInfo
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- CN107011136A CN107011136A CN201710404710.4A CN201710404710A CN107011136A CN 107011136 A CN107011136 A CN 107011136A CN 201710404710 A CN201710404710 A CN 201710404710A CN 107011136 A CN107011136 A CN 107011136A
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- C07C45/515—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups the singly bound functional group being an acetalised, ketalised hemi-acetalised, or hemi-ketalised hydroxyl group
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Abstract
The invention discloses a kind of chemical synthesis process of high-end anti-4 decenal of spices.Occur cross-coupling reaction with n-pentyl magnesium bromide using anti-4 pentenals of 5 bromines as initiation material, after protection aldehyde radical and obtain anti-4 decenal diformazan acetal, anti-4 decenal is obtained after solution protection.It is an advantage of the invention that raw material is cheap and easy to get, synthetic route is simple, and reaction condition is gentle, convenient and safe operation, and yield is high, and cost is low, it is easy to industrialized production.
Description
Technical field
The present invention relates to organic synthesis field, more particularly to a kind of synthetic method of trans- 4- decenals.
Background technology
Trans- 4- decenals are one of most influential fragrance components of in the market, are water insoluble colourless to slightly yellow liquid
Body, stability is good in all cases, is a kind of diffusivity very strong compound.It has a kind of multiple fragrance, there is aldehyde perfume, mandarin orange
Tangerine, the blue or green fragrant, fragrance of a flower, are mainly used as head perfume, and produce the fragrant effect of fresh, natural and similar tangerine, and flavouring effect is very big, product
Aldehyde is fragrant, the persistence for having dish and blue or green fragrant note, or even has influence on the tail rhythm of essence.Trans- 4- decenals can be used for daily chemical essence
In formula, such as in perfumed soap, shampoo or detergent, consumption is generally micro~and 1%.
Trans- 4- decenals belong to high-end spices, and price is expensive, are currently in pilot-scale production, the only U.S.
The only a few manufacturer production such as Bedoukian companies and Qi Huadun companies of Switzerland.The synthetic method of trans- 4- decenals is usually at present
Acetylide reducing process：4- decine alcohol is obtained with suitable alkynol and the coupling of suitable bromoalkane, then trans hydrogenation obtains the trans- 4- last of the ten Heavenly stems
Olefine aldehydr)；Special hydrogenation method：2E4E- decadinene alcohol rhodium catalyst hydrogenation obtains trans- 4- decenals；Special trans null method：Two
Chlorine oxinane obtains double bond with being eliminated after grignard reagent reacting with metallic sodium.These synthetic method expensive starting materials, complex process,
Stereoselectivity is poor, low yield, it is difficult to industrialized production.
The content of the invention
In view of this, it is an object of the invention to provide a kind of raw material is cheap and easy to get, synthetic route is simple, stereoselectivity
The synthetic method of 4 high trans- decenals.
In order to realize foregoing invention purpose, the present invention provides following technical scheme：
A kind of synthetic method of trans- 4- decenals, including following reactions steps：
1) the bromo- trans- 4- pentenals of 5-, trimethyl orthoformate, acidic catalyst and methanol are mixed and carries out aldehyde radical protection instead
Should, obtain the bromo- trans- 4- pentenals diformazan acetals of 5-；
2) by the bromo- trans- 4- pentenals diformazan acetals of the 5-, n-pentyl magnesium bromide and organo-metallic catalyst anhydrous
Cross-coupling reaction is carried out in organic solvent, trans- 4- decenals diformazan acetal is obtained, the anhydrous organic solvent is anhydrous benzene class
Organic solvent or anhydrous ether organic solvent；
3) the trans- 4- decenals diformazan acetal is mixed into the solution protection of progress aldehyde radical with acetone, acid reagent to react, obtained
Trans- 4- decenals.
Preferably, the step 1) in the amounts of material of the bromo- trans- 4- pentenals of 5-, the amount of the material of trimethyl orthoformate,
The amount of the material of acidic catalyst and the volume ratio of methanol are 1mol:1.2~2mol:10~25mmol:500~1500mL.
Preferably, the step 1) in aldehyde radical protection reaction time be 10~30h.
Preferably, the step 2) in the amounts of material of the bromo- trans- 4- pentenals diformazan acetals of 5-, n-pentyl magnesium bromide
The amount of material, the volume ratio of the amount of the material of organo-metallic catalyst and anhydrous organic solvent be 1mol:1.0~1.5mol:
2.5~3.5mmol:450~550mL.
Preferably, the step 2) in organo-metallic catalyst for four (triphenylphosphines) close palladium, double (triphenylphosphines) two
Double (diphenyl phosphine oxide) Nickel Chlorides of palladium bichloride, double (triphenylphosphine) Nickel Chlorides, 1,2- and the double (diphenylphosphines third of 1,3-
Alkane) one or more in Nickel Chloride.
Preferably, the step 2) in benzene class organic solvent be benzene or toluene；
The ether organic solvent is ether, methyl tertiary butyl ether(MTBE), tetrahydrofuran or methyltetrahydrofuran.
Preferably, the step 2) in the temperature of cross-coupling reaction be 0~5 DEG C, time of cross-coupling reaction for 5~
15h。
Preferably, the step 3) in acid reagent be hydrochloric acid, sulfuric acid or acetic acid；
The pH value of the aldehyde radical solution protection reaction is 1~3.
Preferably, the step 3) in trans- 4- decenals diformazan acetal material amount and acetone volume, acid try
The amount ratio of the material of agent is 1mol：500~1000mL:0.025mol~0.5mol.
Preferably, the step 3) in aldehyde radical solution protection reaction time be 3~6h.
Advantageous effects：The method that the present invention is provided is with the bromo- trans- 4- pentenals of 5-, trimethyl orthoformate and n-pentyl
Magnesium bromide etc. is raw material, and raw material is cheap and easy to get；Solvent for use is general chemical raw material, reduces production cost；The present invention is provided
Method obtain trans- 4- decenals by aldehyde radical protection, cross-coupling and aldehyde radical solution protection three-step reaction, synthetic route is simple,
The production cycle is effectively shortened, and reaction condition is gentle, convenient and safe operation, except cross-coupling reaction needs anhydrous and oxygen-free
Outside, remaining 2 step belongs to simple reaction, is adapted to industrialized production；The raw materials used bromo- trans- 4- pentenals of 5- of the present invention it is trans different
Structure purity>99%, cross-coupling reaction does not interfere with cis-trans isomerism purity, therefore the cis-trans isomerism purity of target product>99%,
Stereoselectivity is high.
Brief description of the drawings
Fig. 1 is the gas chromatogram of the gas chromatogram of the trans- 4- decenals of products therefrom in embodiment 1.
Embodiment
The invention provides a kind of synthetic method of trans- 4- decenals, including following reactions steps：
1) the bromo- trans- 4- pentenals of 5-, trimethyl orthoformate, acidic catalyst and methanol are mixed and carries out aldehyde radical protection instead
Should, obtain the bromo- trans- 4- pentenals diformazan acetals of 5-；
2) by the bromo- trans- 4- pentenals diformazan acetals of the 5-, n-pentyl magnesium bromide, catalyst and anhydrous benzene class or ether
The mixing of class organic solvent carries out cross-coupling reaction, obtains trans- 4- decenals diformazan acetal；
3) the trans- 4- decenals diformazan acetal is mixed into the solution protection of progress aldehyde radical with acetone, acid reagent to react, obtained
Trans- 4- decenals.
The present invention is using the bromo- trans- 4- pentenals of 5-, trimethyl orthoformate and methanol as raw material, in the catalysis of acidic catalyst
Lower progress aldehyde radical protection reaction, obtains the bromo- trans- 4- pentenals diformazan acetals of 5-.
In the present invention, the preparation method of the bromo- trans- 4- pentenals of the 5- preferably comprises following steps：
Methacrylaldehyde, lithium bromide, lead acetate, acetic acid are mixed into obtain mixed liquor with water；
Acetylene is passed through into the mixed liquor to carry out after coupling reaction；
The coupling reaction liquid is neutralized to neutrality, through extracting, washing, dry, be concentrated to give 5 bromo- trans- 4- pentenals.
The in the mixed solvent that methacrylaldehyde, lithium bromide and lead acetate are dissolved in acetic acid and water is preferably obtained mixed liquor by the present invention.
In the present invention, the ratio between the methacrylaldehyde, lithium bromide, amount of material of lead acetate and acetic acid are preferably 1mol：0.6~1.5mol：
0.8~5mmol：1.5~2.5mol, more preferably 1mol：0.8~1.3mol：1~4mol：1.8~2.3mol；The acetic acid
Mol ratio with water is preferably 1.5~2.5：1, more preferably 1.8~2.3：1.
Obtain after mixed liquor, acetylene is passed through progress coupling reaction in the mixed liquor and obtains reaction solution by the present invention.In this hair
Acetylene described in bright is preferably handled before through concentrated sulfuric acid gas washing；The intake of the acetylene is the amount of the material of methacrylaldehyde
2~10 times, speed is passed through for 1-5L/h；The concentration of the concentrated sulfuric acid is preferably 98%.In the present invention, the coupling reaction temperature
Degree is preferably room temperature；The time of the coupling reaction is preferably 40~120h, more preferably 60~100h, most preferably 80~
90h；The reaction time when acetylene gas is passed through clock.
Obtain after reaction solution, reaction solution is neutralized to neutrality by the present invention, in the present invention, the neutralization is preferably to use saturation
Na2CO3Solution is neutralized.
Organic phase and aqueous phase are separated after neutralization reaction, after being extracted to aqueous phase, merges organic phase.Present invention preferably employs
Ether is extracted to aqueous phase.
After the extraction, the present invention is washed, dried and is concentrated to give 5 bromo- trans- 4- amylenes to obtained organic phase
Aldehyde.
The present invention is not particularly limited to described, washing, dry, concentration, from this area conventional method.In this hair
In bright, the drying is preferably to be dried with anhydrous sodium sulfate；The concentration is preferably to be carried out using the method for heating evaporation
Concentration, be concentrated into it is solvent-free steam, the evaporating temperature is preferably 20~60 DEG C, more preferably 40 DEG C.
Obtain after the bromo- trans- 4- pentenals of 5-, it is of the invention by the bromo- trans- 4- pentenals of 5-, trimethyl orthoformate, acidic catalyst
Agent and methanol mixing carry out aldehyde radical protection reaction.
The bromo- trans- 4- pentenals of 5- are preferably dissolved in methanol by the present invention, obtain the bromo- trans- 4- pentenals solution of 5-；Again will
The bromo- trans- 4- pentenals solution of 5- is mixed with trimethyl orthoformate and acidic catalyst.In the present invention, described 5 is bromo- trans-
4- pentenals, trimethyl orthoformate, the volume ratio of the amount of the material of acidic catalyst and methanol are preferably 1mol:1.2~2mol:
10~25mmol:500~1500mL, more preferably 1mol:1.5~2.5mol:15~20mmol:800~1200mL；The acid
Property catalyst is preferably p-methyl benzenesulfonic acid, sulfuric acid or ion exchange resin.
In the present invention, the temperature of the aldehyde radical protection reaction is preferably room temperature, without extra heating or cooling；The aldehyde
The time of base protection reaction is preferably 10~30h, more preferably 15~25h, most preferably 18~22h.
After aldehyde radical protection reaction, the present invention is preferred to neutralize the aldehyde radical protection reaction solution for obtaining neutrality.In the present invention, it is described
Neutralization is preferably sodium carbonate, sodium acid carbonate, potassium carbonate, saleratus, sodium hydroxide, potassium hydroxide, more preferably carbon with reagent
Sour sodium or sodium acid carbonate.
Solution is stood after neutralization reaction and is divided into organic layer and water layer, organic layer is isolated, after being extracted to organic layer
Extract.In the present invention, the extraction agent is preferably dichloromethane, and the extraction times are preferably 2~5 times, more preferably
For 3 times；The present invention is not particularly limited to the method for separating organic layer, from the conventional method of this area.
Obtain after extract, the present invention obtains the bromo- trans- 4- pentenals two of 5- after the extract is dried, concentrated
Methanol acetal.
The present invention is not particularly limited to method that is described, drying and concentrate, from this area conventional method.At this
In invention, the dried reagent is preferably natrium carbonicum calcinatum；The method of the concentration is preferably the method being evaporated off, described that temperature is evaporated off
Degree is preferably 20~60 DEG C, more preferably 40 DEG C.
Obtain after the bromo- trans- 4- pentenals dimethanol contractings of 5-, the present invention contracts the bromo- trans- 4- pentenals dimethanols of the 5-
Aldehyde, n-pentyl magnesium bromide, catalyst and anhydrous benzene class or ether organic solvent mixing carry out cross-coupling reaction.
The 5- bromo- trans- 4- pentenals diformazan acetal and organo-metallic catalyst are preferably dissolved in by the present invention anhydrous to be had
Mixed solution is obtained in machine solvent, then the mixed liquor is mixed into progress cross-coupling reaction with n-pentyl magnesium bromide.
In the present invention, the organo-metallic catalyst is preferably that four (triphenylphosphines) close palladium, double (triphenylphosphine) dichloros
Change double (diphenyl phosphine oxide) Nickel Chlorides of palladium, double (triphenylphosphine) Nickel Chlorides, 1,2- and 1,3- is double (diphenylphosphine propane)
One or more in Nickel Chloride, more preferably double (triphenylphosphine) palladium chloride, double (triphenylphosphine) Nickel Chlorides and 1,
It is one or more in double (diphenylphosphine propane) Nickel Chlorides of 3-；Most preferably double (triphenylphosphine) palladium chlorides and double (triphens
Base phosphine) Nickel Chloride, double (triphenylphosphine) palladium chlorides and 1,3- double (diphenylphosphine propane) Nickel Chloride, double (triphenylphosphines)
One kind in palladium chloride and double (diphenylphosphine propane) Nickel Chlorides of 1,3-.
In the present invention, the benzene class organic solvent is preferably benzene or toluene；The ether organic solvent be preferably ether,
Methyl tertiary butyl ether(MTBE), tetrahydrofuran or methyltetrahydrofuran, more preferably tetrahydrofuran or methyltetrahydrofuran.In the present invention
In, the amount of the amount of the material of the bromo- trans- 4- pentenals diformazan acetals of 5- and the material of catalyst, anhydrous organic solvent
Volume ratio is preferably 1mol:2.5~3.5mmol:450~550mL, more preferably 1mol:2.7~3.3mmol:470~
530mL。
Obtain after mixed solution, the present invention will mix progress cross-coupling with n-pentyl magnesium bromide in the mixed liquor anti-
Should.
In the present invention, the n-pentyl magnesium bromide, which is preferably first dissolved in the organic solvent of anhydrous benzene class or ethers, obtains
N-pentyl magnesium bromide organic solution.In the present invention, the benzene class organic solvent is preferably benzene or toluene；The ethers is organic molten
Agent is preferably ether, methyl tertiary butyl ether(MTBE), tetrahydrofuran or methyltetrahydrofuran, more preferably hydrogen furans or methyl tetrahydrochysene furan
Mutter；The concentration of the n-pentyl magnesium bromide organic solution is preferably 1~1.5mol/L, more preferably 1.2~1.4mol/L.
Obtain after n-pentyl magnesium bromide organic solution, the preferred n-pentyl magnesium bromide organic solution is added drop-wise to by the present invention
Cross-coupling reaction is carried out in the mixed liquor.In the present invention, the n-pentyl magnesium bromide organic solution is preferably in frozen water
It is added drop-wise under bath cooling in the mixed liquor, the rate of addition is preferably 60 drops/min.In the present invention, the n-amyl bromide
The mol ratio for changing magnesium and the bromo- trans- 4- pentenals diformazan acetals of the 5- is preferably 1~1.5：1, more preferably 1.2~1.4：
1。
In the present invention, the temperature of the cross-coupling reaction is preferably 0~5 DEG C；The time of the cross-coupling reaction
Preferably 5~15h, more preferably 8~12h.
After the cross-coupling reaction, the present invention adds quencher preferably into the reaction solution after cross-coupling reaction and is quenched
Reaction.In the present invention, the quencher is preferably saturated ammonium chloride solution, and the consumption of the quencher is preferably anhydrous organic
0.2~1 times of solvent volume, more preferably 0.5 times.
It is quenched after reaction and obtains that reaction solution is quenched, the present invention is preferably evaporated off the organic solvent being quenched in reaction solution, obtained
To containing the molten reaction solution of trans- 4- decenals diformazan acetal.In the present invention, the temperature that is evaporated off is preferably 70~30 DEG C, more
Preferably 50 DEG C；Described to be evaporated off the time be preferably 1~4h, more preferably 2.5h.
The present invention takes filtrate after the reacting liquid filtering containing trans- 4- decenals diformazan acetal after solvent being evaporated off, institute
State and trans- 4- decenals diformazan acetal is included in filtrate.In the present invention, the filtering is preferably that pad diatomite is filtered；
Obtain after filtrate, the present invention preferably will obtain trans- 4- decenals diformazan after filtrate extraction, dry, vacuum distillation
Acetal.
The present invention is not particularly limited to the method for extraction, dry, filtering, vacuum distillation, from this area conventional method
.The extraction is preferably to be extracted with ethyl acetate；The extractant of the extraction is preferably ethyl acetate, the extraction
The consumption of agent is preferably 0.5~2 times of anhydrous organic solvent volume, and the drying is preferably to be dried with anhydrous sodium sulfate,
The quality of drier is 5 with extractant volume ratio：100(g/ml)；The temperature of the vacuum distillation is preferably 4~60 DEG C, more excellent
Elect 50 DEG C as, the pressure of the vacuum distillation is preferably 0.1~0.3atm, and more preferably 0.2atm, the time of vacuum distillation is excellent
Elect 2~4 hours, more preferably 3 hours as.
Obtain after trans- 4- decenals diformazan acetal, the present invention will the trans- 4- decenals diformazan acetal and acetone,
Acid reagent mixing carries out the protection reaction of aldehyde radical solution, obtains trans- 4- decenals.In the present invention, the acid reagent is preferably
Hydrochloric acid, sulfuric acid, p-methyl benzenesulfonic acid, trifluoroacetic acid, trifluoromethanesulfonic acid or acetic acid, more preferably hydrochloric acid, sulfuric acid or acetic acid；The acid
The concentration of property reagent is preferably 0.1~0.5mol/L, more preferably 0.2mol/L；In the present invention, the trans- 4- decenals two
The ratio between sour amount of material is preferably 1mol in the amount of the material of methanol acetal and the volume of acetone, acid reagent：
500~1000mL:0.025mol~0.5mol, more preferably 1mol：700~900mL:0.1mol~0.3mol.
In the present invention, the pH value of the aldehyde radical solution protection reaction is preferably 0~3.
In the present invention, the aldehyde radical solution protection reaction time is preferably 3~6h, more preferably 2~5h；The aldehyde radical solution
The temperature of protection reaction is preferably room temperature, without extra heating or cooling.
Reaction solution is obtained after the protection reaction of aldehyde radical solution, the present invention after reaction solution is obtained and reaction solution is neutralized to neutrality, in this hair
In bright, the neutralization reagent be preferably sodium carbonate, sodium acid carbonate, potassium carbonate, saleratus, sodium hydroxide, potassium hydroxide, more
Preferably sodium carbonate, sodium acid carbonate.
Solvent is evaporated off after neutralization reaction, the reaction solution containing trans- 4- decenals is obtained.The solvent that is evaporated off described in the present invention
Temperature is preferably 20~60 DEG C, more preferably 40 DEG C；Described to be evaporated off the time be preferably 2~5 hours, more preferably 3 hours.
Obtain after the reaction solution containing trans- 4- decenals, the present invention obtains reaction solution extraction, dry, vacuum distillation
To trans- 4- decenals.The present invention is not particularly limited to the method for extraction, dry, vacuum distillation, from this area conventional method
.In the present invention, the extraction is preferably to be extracted from dichloromethane, and the drying is preferably to use anhydrous slufuric acid
Sodium is dried；The temperature of the vacuum distillation is preferably 20~40 DEG C, and pressure is preferably 0.1~0.3atm.
A kind of synthetic method of the trans- 4- decenals provided with reference to embodiment the present invention is described in detail,
But they can not be interpreted as limiting the scope of the present invention.
Embodiment 1
1) preparation of the bromo- trans- 4- pentenals of 5-：By methacrylaldehyde (168g, 3mol), LiBr (261g, 3mol) and Pd (Ac)2
(560mg, 2.5mmol) is dissolved in HAc (270g, 4.5mol) and H2O (54g, 3mol) in the mixed solvent, is passed through through sulfuric acid gas washing
The acetylene of processing, is stirred at room temperature reaction 72h, uses saturation Na2CO3Solution is neutralized to neutrality, separates organic layer, water layer with 3 ×
200mL Et2O is extracted, and is merged organic layer and is washed with water, through anhydrous Na2SO4Dry and be evaporated off after solvent obtaining reaction product
248g, yield 61% can be used to next step reaction without separation.
Obtained reaction product is subjected to proton nmr spectra and carbon spectrum detection, structured data is：
1H NMR(CDCl3,400MHz)δ:9.77 (s, 1H, CHO), 6.12 (d, J=13.6Hz, 1H, BrCH=CH),
6.15~6.22 (m, 1H, BrCH=CH), 2.58 (m, 2H), 2.38 (m, 2H)；13C NMR(CDCl3,100MHz)δ:200.7,
135.8,106.0,42.5,25.4. data result is shown as the bromo- trans- 4- pentenals of 5-.
The preparation of the bromo- trans- 4- pentenals diformazan acetals of 5-：The trans- pentenals (163g, 1mol) of 5- bromo- 4 are dissolved in
In 1000mL methanol, trimethyl orthoformate (178g, 1.2mol) and p-methyl benzenesulfonic acid (3.8g, 20mmol) are added, at room temperature instead
Answer after 10 hours, add saturated sodium carbonate solution and neutralize, separate organic layer, then extracted 2 times with dichloromethane, through anhydrous sodium sulfate
Dry and be evaporated off after solvent obtaining reactant 225g, yield 95%, further separation is directly used in next step reaction.
The structural characterization data of the reaction product are as follows：
1H NMR(CDCl3,400MHz)δ:6.17 (m, 1H, BrCH=CH), 6.02 (d, J=14.2Hz, 1H, BrCH=
), CH 4.28 (t, J=5.7Hz, 1H ,-OCHO-), 3.24 (s, 6H, OCH3), 2.13 (m, 2H, CH2), 1.64 (m, 2H, CH2)
；13C NMR(CDCl3,100MHz)δ:It is bromo- trans- that 135.7,106.2,103.7,52.8,32.0,26.1. data result is shown as 5
4- pentenals diformazan acetals.
2) preparation of trans- 4- decenals diformazan acetal：Under nitrogen protection, the bromo- trans- 4- pentenals dimethanols of 5- are contracted
Aldehyde (213g, 0.9mol) and double (diphenylphosphine propane) Nickel Chlorides (1629mg, 3mmol) of 1,3- are dissolved in 450mL anhydrous methyls
In tetrahydrofuran, the 1200mL anhydrous methyl tetrahydrofuran solutions of n-pentyl magnesium bromide (1.2mol) prepared by conventional method are in ice
It is added drop-wise under water-bath cooling in above-mentioned reactant mixture, continues to react 12 hours, is added saturated ammonium chloride solution and reaction is quenched, steam
Except methyltetrahydrofuran, pad diatomite is filtered to remove after reaction residues, is extracted with ethyl acetate 3 times, organic layer is through anhydrous slufuric acid
Sodium is dried and is evaporated off after solvent obtaining residue, and vacuum distillation obtains reaction product 91g, yield 93%.
The structural characterization data of wherein described reaction product are as follows：
1H NMR(CDCl3,300MHz)δ:5.40 (m, 2H ,-CH=CH-), 4.34 (t, J=4.1Hz, 1H ,-OCHO-),
3.30(s,6H,OCH3),2.20(m,2H,CH2),2.07(m,2H,CH2),1.64(m,2H,CH2),1.40–1.20(m,6H,
), CH2CH2 0.90 (t, J=6.6Hz, 3H, CH3)；13C NMR(CDCl3,100MHz)δ:131.9,128.7,104.0,52.7,
32.5,32.4,31.9,31.5,22.9,22.2,13.9.℃.Data result shows that reaction product is trans- 4- decenals dimethanol
Acetal.
3) preparation of trans- 4- decenals：Trans- 4- decenals diformazan acetal (182g, 0.8mol) is dissolved in 800mL acetone
In, hydrochloric acid (40mL, 1mol/L) is added, reaction is stopped after reacting 5 hours at room temperature, saturated sodium carbonate solution is added and is neutralized to
Neutrality, is steamed after acetone, is added dichloromethane and is extracted 3 times, organic layer is remained through anhydrous sodium sulfate drying and after solvent is evaporated off
Excess, vacuum distillation obtains reaction product 112g, yield 91%.
The structural characterization data of the reaction product are as follows：
1H NMR(CDCl3,400MHz)δ:9.76 (s, 1H, CHO), 5.47~5.31 (m, 2H, CH=CH), 2.45 (m,
2H, CH2CHO), 2.20 (m, 2H, CH2), 2.01 (m, 2H, CH2), 1.40-1.20 (m, 6H, CH2), 0.90 (t, J=6.9Hz,
3H,CH3)；13C NMR(CDCl3,100MHz)δ:202.7,131.9,128.7,43.1,32.7,31.7,31.8,27.6,
22.4,14.1. data result shows that the reaction product is trans- 4- decenals.
Fig. 1 be embodiment 1 in the trans- 4- decenals of products therefrom gas chromatogram gas chromatogram, the product it is suitable
Anti- isomeric purities>99%, stereoselectivity is high.
Embodiment 2
1) preparation of the bromo- trans- 4- pentenals of 5-：By methacrylaldehyde (224g, 4mol), LiBr (261g, 3mol) and Pd (Ac)2
(4480mg, 20mmol) is dissolved in HAc (360g, 6mol) and H2O (54g, 3mol) in the mixed solvent, is passed through through at sulfuric acid gas washing
The acetylene of reason, is stirred at room temperature reaction 96h, uses saturation Na2CO3Solution is neutralized to neutrality, separates organic layer, water layer with 3 ×
400mL dichloromethane is extracted, and is merged organic layer and is washed with water, through anhydrous Na2SO4Dry and be evaporated off after solvent 5- is bromo- trans-
4- pentenals 406g, yield 83% (is calculated) with LiBr, and next step reaction is can be used to without separation.
The preparation of the bromo- trans- 4- pentenals diformazan acetals of 5-：The trans- pentenals (326g, 2mol) of 5- bromo- 4 are dissolved in
In 1000mL methanol, trimethyl orthoformate (371g, 2.5mol) and sulfuric acid (1.96g, 20mmol) are added, 12 are reacted at room temperature small
Shi Hou, adds saturated sodium carbonate solution and neutralizes, separate organic layer, then extracts 2 times with dichloromethane, through anhydrous sodium sulfate drying simultaneously
It is evaporated off after solvent obtaining the bromo- trans- 4- pentenals diformazan acetal 436g of residue, i.e. 5-, yield 92% is not separated further direct
For next step reaction.
2) preparation of trans- 4- decenals diformazan acetal：Under nitrogen protection, the bromo- trans- 4- pentenals dimethanols of 5- are contracted
Aldehyde (237g, 1mol) and double (diphenylphosphine propane) Nickel Chlorides (1629mg, 3mmol) of 1,3- are dissolved in 500mL anhydrous methyls four
In hydrogen furans, the 1500mL anhydrous methyl tetrahydrofuran solutions of n-pentyl magnesium bromide (1.5mol) prepared by conventional method method are in ice
It is added drop-wise under water-bath cooling in above-mentioned reactant mixture, continues to react 24 hours, is added saturated ammonium chloride solution and reaction is quenched, steam
Except methyltetrahydrofuran, pad diatomite is filtered to remove after reaction residues, is extracted with ethyl acetate 3 times, organic layer is through anhydrous slufuric acid
Sodium is dried and is evaporated off after solvent obtaining residue, and vacuum distillation obtains 4 trans- decenal diformazan acetal 182g, yield 91%.
3) preparation of trans- 4- decenals：Trans- 4- decenals diformazan acetal (200g, 1mol) is dissolved in 600mL acetone
In, acetic acid (400mL) is added, reaction is stopped after being reacted 6 hours at 60 DEG C, saturated sodium carbonate solution is added and is neutralized to neutrality, steam
Go out after acetone, add dichloromethane and extract 3 times, organic layer obtains residue through anhydrous sodium sulfate drying and after solvent is evaporated off, and subtracts
Pressure distillation obtains trans- 4- decenals 145g, yield 94%.
Embodiment 3
1) preparation of the bromo- trans- 4- pentenals of 5-：By methacrylaldehyde (168g, 3mol), LiBr (348g, 4mol) and Pd (Ac)2
(2240mg, 10mmol) is dissolved in HAc (420g, 7mol) and H2O (54g, 3mol) in the mixed solvent, is passed through through at sulfuric acid gas washing
The acetylene of reason, is stirred at room temperature reaction 60h, uses saturation Na2CO3Solution is neutralized to neutrality, separates organic layer, water layer with 3 ×
200mL Et2O is extracted, and is merged organic layer and is washed with water, through anhydrous Na2SO4Dry and be evaporated off after solvent obtaining the bromo- trans- 4- penta of 5-
Olefine aldehydr 318g, yield 65% (is calculated) with methacrylaldehyde, and next step reaction is can be used to without separation.
The preparation of the trans- pentenals diformazan acetals of 5- bromo- 4：5 bromo- trans- 4- pentenals (163g, 1mol) are dissolved in
In 1000mL ethanol, trimethyl orthoformate (223g, 1.5mol) and p-methyl benzenesulfonic acid (3.8g, 20mmol) are added, at room temperature instead
Answer after 10 hours, add saturated sodium carbonate solution and neutralize, separate organic layer, then extracted 2 times with dichloromethane, through anhydrous sodium sulfate
Dry and be evaporated off after solvent obtaining bromo- trans- 4- pentenals diformazan acetal (3) 216g of residue, i.e. 5-, yield 91% does not enter one
Step separation is directly used in next step reaction.
2) preparation of trans- 4- decenals diformazan acetal：Under nitrogen protection, the bromo- trans- 4- pentenals dimethanols of 5- are contracted
Aldehyde (237g, 1mol) and tetrakis triphenylphosphine palladium (3468mg, 3mmol) are dissolved in 500mL anhydrous methyl tetrahydrofurans, routine side
The 1500mL anhydrous methyls tetrahydrofuran solution of n-pentyl magnesium bromide (1.5mol) prepared by method is added drop-wise under ice-water bath cooling
In above-mentioned reactant mixture, continue to react 12 hours, add saturated ammonium chloride solution and reaction is quenched, methyltetrahydrofuran is evaporated off,
Pad diatomite is filtered to remove after reaction residues, is extracted with ethyl acetate 3 times, organic layer is through anhydrous sodium sulfate drying and solvent is evaporated off
After obtain residue, vacuum distillation obtains trans- 4- decenals diformazan acetal 184g, yield 92%.
3) preparation of trans- 4- decenals：Trans- 4- decenals diformazan acetal (200g, 1mol) is dissolved in 500mL acetone
In, sulfuric acid (25mL, 1mol/L) is added, reaction is stopped after reacting 3 hours at room temperature, saturated sodium carbonate solution is added and is neutralized to
Neutrality, is steamed after acetone, is added dichloromethane and is extracted 3 times, organic layer is remained through anhydrous sodium sulfate drying and after solvent is evaporated off
Excess, vacuum distillation obtains trans- 4- decenals 134g, yield 87%.
Described above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (10)
1. a kind of synthetic method of trans- 4- decenals, it is characterised in that including following reactions steps：
1) the bromo- trans- 4- pentenals of 5-, trimethyl orthoformate, acidic catalyst and methanol are mixed and carries out aldehyde radical protection reaction, obtained
The bromo- trans- 4- pentenals diformazan acetals of 5-；
2) by the bromo- trans- 4- pentenals diformazan acetals of the 5-, n-pentyl magnesium bromide and organo-metallic catalyst anhydrous organic
Cross-coupling reaction is carried out in solvent, trans- 4- decenals diformazan acetal is obtained, the anhydrous organic solvent is that anhydrous benzene class is organic
Solvent or anhydrous ether organic solvent；
3) the trans- 4- decenals diformazan acetal is mixed into the solution protection of progress aldehyde radical with acetone, acid reagent to react, obtains trans-
4- decenals.
2. synthetic method according to claim 1, it is characterised in that the step 1) in the bromo- trans- 4- pentenals of 5- thing
The amount of matter, the amount of the material of trimethyl orthoformate, the volume ratio of the amount of the material of p-methyl benzenesulfonic acid and methanol are 1mol:1.2~
2mol:10~25mmol:500~1500mL.
3. synthetic method according to claim 1 or 2, it is characterised in that the step 1) in aldehyde radical protection reaction when
Between be 10~30h.
4. synthetic method according to claim 1, it is characterised in that the step 2) in the bromo- trans- 4- pentenals diformazans of 5-
The amount of the material of acetal, the amount of the material of n-pentyl magnesium bromide, the amount of the material of organo-metallic catalyst and anhydrous organic molten
The volume ratio of agent is 1mol:1.0~1.5mol:2.5~3.5mmol:450~550mL.
5. synthetic method according to claim 1, it is characterised in that the step 2) in organo-metallic catalyst include
Four (triphenylphosphines) close double (the diphenylphosphine second of palladium, double (triphenylphosphine) palladium chlorides, double (triphenylphosphine) Nickel Chlorides, 1,2-
Alkane) one or more in double (diphenylphosphine propane) Nickel Chlorides of Nickel Chloride and 1,3-.
6. synthetic method according to claim 1, it is characterised in that the step 2) in benzene class organic solvent be benzene or first
Benzene；
The ether organic solvent is ether, methyl tertiary butyl ether(MTBE), tetrahydrofuran or methyltetrahydrofuran.
7. the synthetic method according to any one of claim 1 or 4~6, it is characterised in that the step 2) in intersect it is even
The temperature of connection reaction is 0~5 DEG C, and the time of cross-coupling reaction is 5~15h.
8. synthetic method according to claim 1, it is characterised in that the step 3) in acid reagent be hydrochloric acid, sulfuric acid
Or acetic acid；
The pH value of the aldehyde radical solution protection reaction is 0~3.
9. synthetic method according to claim 8, it is characterised in that the step 3) in trans- 4- decenals dimethanol contracting
The amount of the material of aldehyde and the volume of acetone, the amount ratio of the material of acid reagent are 1mol：500~1000mL:0.025mol~
0.5mol。
10. synthetic method according to claim 1, it is characterised in that the step 3) in the protection reaction of aldehyde radical solution when
Between be 3~6h.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1221725A (en) * | 1997-11-27 | 1999-07-07 | 霍夫曼-拉罗奇有限公司 | Manufacure of polyene aldehydes |
| CN1557796A (en) * | 2004-01-21 | 2004-12-29 | 云南大学 | Process for synthesizing sex pheromone of pine caterpillar |
| CN102060679A (en) * | 2009-11-18 | 2011-05-18 | 中国中化股份有限公司 | Method for preparing aryl propanal derivatives |
| CN106431831A (en) * | 2016-09-18 | 2017-02-22 | 昆明博鸿生物科技有限公司 | Synthesizing method for 5E-decene-1-alcohol and acetic acid 5E-decenoate |
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2017
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1221725A (en) * | 1997-11-27 | 1999-07-07 | 霍夫曼-拉罗奇有限公司 | Manufacure of polyene aldehydes |
| CN1557796A (en) * | 2004-01-21 | 2004-12-29 | 云南大学 | Process for synthesizing sex pheromone of pine caterpillar |
| CN102060679A (en) * | 2009-11-18 | 2011-05-18 | 中国中化股份有限公司 | Method for preparing aryl propanal derivatives |
| CN106431831A (en) * | 2016-09-18 | 2017-02-22 | 昆明博鸿生物科技有限公司 | Synthesizing method for 5E-decene-1-alcohol and acetic acid 5E-decenoate |
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