CN110372654A - The method of two-step method synthesis 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one - Google Patents
The method of two-step method synthesis 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one Download PDFInfo
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- CN110372654A CN110372654A CN201910640909.6A CN201910640909A CN110372654A CN 110372654 A CN110372654 A CN 110372654A CN 201910640909 A CN201910640909 A CN 201910640909A CN 110372654 A CN110372654 A CN 110372654A
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- 238000000034 method Methods 0.000 title claims abstract description 49
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 29
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 29
- LMCDKONPVQNISE-UHFFFAOYSA-N 4-methyl-6-(2,4,4-trimethylpentyl)pyran-2-one Chemical compound CC(C)(C)CC(C)CC1=CC(C)=CC(=O)O1 LMCDKONPVQNISE-UHFFFAOYSA-N 0.000 title claims abstract description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 51
- 238000006243 chemical reaction Methods 0.000 claims abstract description 49
- 229960000583 acetic acid Drugs 0.000 claims abstract description 20
- 239000002253 acid Substances 0.000 claims abstract description 15
- -1 3,7,9,9- tetramethyl -2- decene Chemical compound 0.000 claims abstract description 12
- 150000004702 methyl esters Chemical class 0.000 claims abstract description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 11
- GEKPNPPFAYJZRD-UHFFFAOYSA-N 3,5,5-trimethylhexanoyl chloride Chemical compound ClC(=O)CC(C)CC(C)(C)C GEKPNPPFAYJZRD-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000012362 glacial acetic acid Substances 0.000 claims abstract description 9
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims abstract description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 54
- 239000012074 organic phase Substances 0.000 claims description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 40
- 238000004821 distillation Methods 0.000 claims description 32
- 238000003756 stirring Methods 0.000 claims description 22
- 238000010992 reflux Methods 0.000 claims description 17
- 230000006837 decompression Effects 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 13
- 238000013517 stratification Methods 0.000 claims description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 239000008346 aqueous phase Substances 0.000 claims description 12
- 239000000460 chlorine Substances 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- 238000001816 cooling Methods 0.000 claims description 9
- 239000010813 municipal solid waste Substances 0.000 claims description 7
- 230000000630 rising effect Effects 0.000 claims description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 5
- 239000005457 ice water Substances 0.000 claims description 5
- 238000004321 preservation Methods 0.000 claims description 5
- XZOYHFBNQHPJRQ-UHFFFAOYSA-N 7-methyloctanoic acid Chemical compound CC(C)CCCCCC(O)=O XZOYHFBNQHPJRQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000012071 phase Substances 0.000 claims description 4
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 2
- 238000005070 sampling Methods 0.000 claims 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 238000007689 inspection Methods 0.000 claims 1
- 125000001402 nonanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 238000004064 recycling Methods 0.000 claims 1
- 238000005917 acylation reaction Methods 0.000 abstract description 7
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 238000007363 ring formation reaction Methods 0.000 abstract description 7
- 239000003054 catalyst Substances 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 230000003197 catalytic effect Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 18
- 238000001514 detection method Methods 0.000 description 8
- 238000009835 boiling Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 229950001046 piroctone Drugs 0.000 description 5
- BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical compound CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 4
- YYPNJNDODFVZLE-UHFFFAOYSA-N 3-methylbut-2-enoic acid Chemical compound CC(C)=CC(O)=O YYPNJNDODFVZLE-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- BTSZTGGZJQFALU-UHFFFAOYSA-N piroctone olamine Chemical compound NCCO.CC(C)(C)CC(C)CC1=CC(C)=CC(=O)N1O BTSZTGGZJQFALU-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- ORVUCTLMJXASEY-UHFFFAOYSA-N 3-methyldec-2-ene Chemical compound CCCCCCCC(C)=CC ORVUCTLMJXASEY-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 2
- 238000007273 lactonization reaction Methods 0.000 description 2
- FZIBCCGGICGWBP-UHFFFAOYSA-N methyl 3-methylbut-2-enoate Chemical class COC(=O)C=C(C)C FZIBCCGGICGWBP-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- XMNCVHDCPLYBSD-UHFFFAOYSA-N 3-pentylpyran-2-one Chemical compound CCCCCC1=CC=COC1=O XMNCVHDCPLYBSD-UHFFFAOYSA-N 0.000 description 1
- 208000001840 Dandruff Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/34—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D309/36—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
- C07D309/38—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms one oxygen atom in position 2 or 4, e.g. pyrones
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The present invention relates to chemical intermediate synthesis technical fields, particularly disclose a kind of method of two-step method synthesis 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one.The present invention is two-step synthesis method, with isononanoyl chloride, 3,3- methyl methacrylate for raw material, carries out acylation reaction in the catalyst of aluminum trichloride (anhydrous), synthesizes 3,7,9,9- tetramethyl -2- decene -5- ketone acid methyl esters；Later again under the catalytic action of the concentrated sulfuric acid, cyclization reaction is carried out with glacial acetic acid, it is purified to obtain product.For the present invention compared with other process routes, reaction step is few, high income, and product purity is high, and production cost is low, and equipment requirement is few, is suitable for industrialized production.
Description
(1) technical field
The present invention relates to chemical intermediate synthesis technical field, in particular to a kind of two-step method synthesizes 4- methyl -6- (2,4,4- tri-
Methyl amyl) -2H- pyran-2-one method.
(2) background technique
4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one is synthesis compound Octopirox(1- hydroxyl -4- first
Base -6- (2,4,4- front three amyl) -2- Octopirox) important intermediate, since Octopirox has better than similar
The anti-dandruff and itching-relieving effect of product, has the great significance for popularization and prospect of the application.Simultaneously as Octopirox synthesis technology
Complexity, imported raw material higher cost, therefore production development at home is subject to certain restrictions, therefore, study Octopirox and its
The synthesis technology of intermediate, to reduce production cost as urgent need.
The synthesis of intermediate 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one is with 4- methyl -3- penta
Alkene -2- ketone is starting material, and mainly through peroxidization, esterification, acylation reaction, cyclization, four-step reaction is complete altogether
At synthesis specific steps method is as follows:
(1) oxidation reaction
Appropriate sodium hypochlorite is added in 4- methyl -3- amylene -2- ketone, certain time is heated to reflux, by reaction solution tune after cooling
For acidity, 3- methyl-2-butenoic acid, yield 74% is precipitated.Reaction equation is as follows:
；
(2) esterification
Previous step product 3- methyl-2-butenoic acid is mixed with methanol, and using the concentrated sulfuric acid as catalyst, heating reaction obtains esterification and produces
Object 3- methyl-2-butenoic acid methyl esters, or with ethanol synthesis, obtain 3- methyl-2-butene acetoacetic ester, yield 82%.Reaction equation
It is as follows:
,
；
(3) acylation reaction
Previous step product 3- methyl-2-butenoic acid methyl esters or 3- methyl-2-butene acetoacetic ester add with 3,5,5- trimethyl acetyl chlorine
Enter into organic solvent, using aluminum trichloride (anhydrous) as catalyst, after being heated to reflux, cooling reaction solution, then washing is removed
Alchlor, extraction and separation go out organic phase, after organic solvent is evaporated off, obtain product, yield 55%.Reaction equation is as follows:
,
；
(4) cyclization
The step reacts the method in document report are as follows: by previous step product 3,7,9,9- tetramethyl -2- decene -5- ketone acid methyl esters
Or 3,7,9,9- tetramethyl -2- decene -5- keto acid ethyl esters are placed in plume and heat, react at high temperature, obtain 4- methyl -6-
(2,4,4- tri-methyl-amyl) -2- pyranone, yield 70%.Reaction equation is as follows:
。
This kind of method only needs single step reaction can be completed, but experimental provision is relative complex, experimental facilities higher cost, uncomfortable
Close laboratory operation.
Separately there is document report similar structural compound 3- methyl -2- decene -5- ketone acid methyl esters (compound a) anti-through hydrolyzing
It answers, the cyclisation of two step of lactonization reaction.Method particularly includes: first compound a is hydrolyzed to obtain 3- methyl -2- decene -5- ketone acid (chemical combination
Object b) under sulphuric acid catalysis, obtains cyclisation product 4- methyl -6- through lactonization reaction then by compound b in acetic acid solvent
(compound c), the yield that lactonizes is up to 90% for amyl -2- pyranone.Reaction equation is as follows:
。
For this method compared with first method, experimental provision is fairly simple, tests strong operability, and product yield
Height is suitble to laboratory to promote.
But up to now, it is suitable for industrialized production intermediate 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyrrole
The method of -2- ketone of muttering occurs not yet, and the technical problem is urgently to be resolved.
(3) summary of the invention
In order to compensate for the shortcomings of the prior art, the present invention provides a kind of steps, and two-step method simple, that product yield is high synthesizes 4-
The method of methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one.
The present invention is achieved through the following technical solutions:
A kind of method of two-step method synthesis 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one, including walk as follows
It is rapid:
(1) under stirring, aluminum trichloride (anhydrous) is added into methylene chloride, and isononanoyl chloride and 3,3- bis- are successively added dropwise later
Methyl methacrylate, after completion of dropwise addition, heating reaction system to reflux is reacted, and reaction solution is through cooling, standing after the completion
Layering, separates lower layer's organic phase and upper strata aqueous phase, and water phase extracted, merges organic phase, and organic phase is washed, air-distillation, water
Vacuum decompression distillation finally collects vinasse and obtains 3,7,9,9- tetramethyl -2- decene -5- ketone acid methyl esters crude products；
(2) glacial acetic acid, the concentrated sulfuric acid, temperature rising reflux reaction are added in vinasse；Reaction solution is distilled through water vacuum decompression later
After cool down, be added methylene chloride stirring, stratification；Lower layer's organic phase is separated, merges organic phase after extracting upper strata aqueous phase, it is organic
Mutually washed, air-distillation, oil pump distillation, obtain product.
The present invention is two-step synthesis method, with isononanoyl chloride, 3,3- methyl methacrylate for raw material, in anhydrous tri-chlorination
The catalyst of aluminium carries out acylation reaction, synthesizes 3,7,9,9- tetramethyl -2- decene -5- ketone acid methyl esters；The concentrated sulfuric acid is urged again later
Under change effect, cyclization reaction is carried out with glacial acetic acid, it is purified to obtain product.
More excellent technical solution of the invention are as follows:
In step (1), the mass ratio of methylene chloride and aluminum trichloride (anhydrous) is 5:2, and 10min is mixed in the two.
Isononanoyl chloride and 3, for the molar ratio of 3- methyl methacrylate close to 1:1,3,3- methyl methacrylates are micro-
It is excessive；Isononanoyl chloride is slowly added dropwise at 25-30 DEG C, 0.5h is dripped off, and drips off heat preservation 10min, 3,3- diformazan is directly added dropwise later
Base methyl acrylate is to slowly warm up to 36-38 DEG C during being added dropwise, and 1h is dripped.
Reaction system is heated to flowing back, the back flow reaction 4-5h at 41-42 DEG C, sample detection is anti-with no isononanoic acid
Answer terminal；Reaction solution is cooled down to 30 DEG C hereinafter, reaction solution is poured slowly into trash ice under stirring, stirs stratification after 0.5h,
Separate lower layer's organic phase.
Wherein, the trash ice is the rubble ice containing concentrated hydrochloric acid, contains 100g concentrated hydrochloric acid in every 1200g rubble ice.
The water phase separated is extracted with dichloromethane twice, merges organic phase, and organic phase successively uses clear water, saturated sodium bicarbonate
Solution and clear water respectively washed once；Organic phase after air-distillation, is to slowly warm up to 90 DEG C at 60-65 DEG C, at 90 DEG C into
The distillation of row water vacuum decompression, collects vinasse.
In step (2), glacial acetic acid, the concentrated sulfuric acid are added in vinasse, temperature rising reflux reacts 2h, sample detection, until not having
There is 3,7,9,9- tetramethyl -2- decene -5- ketone acid methyl esters to be produced as reaction end.
Water vacuum decompression is distilled to recover acetic acid, until temperature stops distillation when reaching 118-120 DEG C without acetic acid；By Liquid Residue
It pours into ice water, and methylene chloride stirring, stratification is added；Separate lower layer's organic phase.
Upper strata aqueous phase is extracted with dichloromethane twice, merges organic phase, and organic phase uses the hydroxide of mass concentration 5% respectively
Sodium solution washed once, then be washed twice with clear water, separate organic phase；Organic phase is distilled to recover methylene chloride through normal pressure, directly
To liquid temperature to 95 DEG C, pump distillation of changing oil obtains product.
For the present invention compared with other process routes, reaction step is few, high income, and product purity is high, and production cost is low, equipment
It is required that it is few, it is suitable for industrialized production.
(4) specific embodiment
The present invention is further explained in the light of specific embodiments.
Embodiment 1: the method for two-step method synthesis 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one
(1) synthesis (acylation reaction) of 3,7,9,9- tetramethyl -2- decene -5- ketone acid methyl esters
500g CH is added into 1000ml four-hole boiling flask2Cl2, it is added with stirring the anhydrous AlCl of 200g3, stir 10min；In 28
Isononanoyl chloride 89.25g(0.5mol is added dropwise at DEG C), this process heat release is not violent, and about 0.5h is dripped off, and drips off heat preservation 10min；It is not added
Heat, directly dropwise addition 3,3- methyl methacrylate 58.8g(0.51mol), 37 DEG C or so can be slowly ramped to during dropwise addition,
Temperature rise is not violent, but can acutely emit hydrogen chloride gas, and has faint reflux；About 1h is dripped off；
After completion of dropwise addition, heating reaction system to reflux, 41-42 DEG C, back flow reaction 4.5h, sample detection, substantially without different nonyl
Acid is reaction end.Cooling reaction solution is to 30 DEG C hereinafter, that reaction solution is poured slowly into 1200g trash ice under stirring is (dense containing 100g
Hydrochloric acid) in, speed cannot be too fast, otherwise can slug；0.5h is stirred, stratification separates lower layer's organic phase, and upper strata aqueous phase is used
CH2Cl2It is extracted twice, 100g*2, merges organic phase；Organic phase uses 300g clear water, saturated sodium bicarbonate 200g, clear water respectively
300g is respectively washed once；By it is above-mentioned it is organic be added in cucurbit, major part CH are recycled in first 63 DEG C or so air-distillations2Cl2, then delay
Slow heating is finally distilled with water vacuum decompression until not having low-boiling point material at such a temperature until 90 DEG C；Terminate distillation, obtains
About 118g crude product, purity 92%, sterling yield 85.4%.
(2) synthesis (cyclization reaction) of 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one
Previous step vinasse 118g is added in 500ml four-hole bottle, 236g glacial acetic acid, the 11.8g concentrated sulfuric acid, temperature rising reflux is added
2h is reacted, sample detection is reaction end when not having previous step product.Water vacuum decompression is distilled to recover acetic acid, Zhi Daowen
Degree reaches 118-120 DEG C, does not have to stop distillation when acetic acid substantially；Liquid Residue is poured into 300g ice water, and 200g is added
CH2Cl2, stir 0.5h stratification；Separate lower layer's organic phase, upper strata aqueous phase CH2Cl2It is extracted twice, 50g*2, merges organic
Phase；Primary, clear water is washed with 5%NaOH 100g respectively and washes 150*2 twice, separates organic phase；Cucurbit is added to by organic above
In, CH is recycled in air-distillation2Cl2Until liquid temperature reaches 95 DEG C, pump distillation of changing oil obtains product 92.4g, purity 97%；Total recovery
81%。
Embodiment 2: the method for two-step method synthesis 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one
(1) synthesis (acylation reaction) of 3,7,9,9- tetramethyl -2- decene -5- ketone acid methyl esters
500g CH is added into 1000ml four-hole boiling flask2Cl2, it is added with stirring the anhydrous AlCl of 200g3, stir 10min；In 25
Isononanoyl chloride 89.25g(0.5mol is added dropwise at DEG C), this process heat release is not violent, and about 0.5h is dripped off, and drips off heat preservation 10min；It is not added
Heat, directly dropwise addition 3,3- methyl methacrylate 58.8g(0.51mol), 36 DEG C or so can be slowly ramped to during dropwise addition,
Temperature rise is not violent, but can acutely emit hydrogen chloride gas, and has faint reflux；About 1h is dripped off；
After completion of dropwise addition, heating reaction system to reflux, 41-42 DEG C, back flow reaction 4h, sample detection, substantially without isononanoic acid
For reaction end.Cooling reaction solution is to 30 DEG C hereinafter, reaction solution is poured slowly into 1200g trash ice (containing the dense salt of 100g under stirring
Acid) in, speed cannot be too fast, otherwise can slug；0.5h is stirred, stratification separates lower layer's organic phase, and upper strata aqueous phase is used
CH2Cl2It is extracted twice, 100g*2, merges organic phase；Organic phase uses 300g clear water, saturated sodium bicarbonate 200g, clear water respectively
300g is respectively washed once；By it is above-mentioned it is organic be added in cucurbit, major part CH are recycled in first 60 DEG C or so air-distillations2Cl2, then delay
Slow heating is finally distilled with water vacuum decompression until not having low-boiling point material at such a temperature until 90 DEG C；Terminate distillation, obtains
About 120g crude product, purity 90%, sterling yield 84.96%.
(2) synthesis (cyclization reaction) of 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one
Previous step vinasse 118g is added in 500ml four-hole bottle, 236g glacial acetic acid, the 11.8g concentrated sulfuric acid, temperature rising reflux is added
2h is reacted, sample detection is reaction end when not having previous step product.Water vacuum decompression is distilled to recover acetic acid, Zhi Daowen
Degree reaches 118-120 DEG C, does not have to stop distillation when acetic acid substantially；Liquid Residue is poured into 300g ice water, and 200g is added
CH2Cl2, stir 0.5h stratification；Separate lower layer's organic phase, upper strata aqueous phase CH2Cl2It is extracted twice, 50g*2, merges organic
Phase；Primary, clear water is washed with 5%NaOH 100g respectively and washes 150*2 twice, separates organic phase；Cucurbit is added to by organic above
In, CH is recycled in air-distillation2Cl2Until liquid temperature reaches 95 DEG C, pump distillation of changing oil obtains product 93.8g, purity 95%；Total recovery
80.53%。
Embodiment 3: the method for two-step method synthesis 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one
(1) synthesis (acylation reaction) of 3,7,9,9- tetramethyl -2- decene -5- ketone acid methyl esters
500g CH is added into 1000ml four-hole boiling flask2Cl2, it is added with stirring the anhydrous AlCl of 200g3, stir 10min；In 30
Isononanoyl chloride 89.25g(0.5mol is added dropwise at DEG C), this process heat release is not violent, and about 0.5h is dripped off, and drips off heat preservation 10min；It is not added
Heat, directly dropwise addition 3,3- methyl methacrylate 58.8g(0.51mol), 38 DEG C or so can be slowly ramped to during dropwise addition,
Temperature rise is not violent, but can acutely emit hydrogen chloride gas, and has faint reflux；About 1h is dripped off；
After completion of dropwise addition, heating reaction system to reflux, 41-42 DEG C, back flow reaction 5h, sample detection, substantially without isononanoic acid
For reaction end.Cooling reaction solution is to 30 DEG C hereinafter, reaction solution is poured slowly into 1200g trash ice (containing the dense salt of 100g under stirring
Acid) in, speed cannot be too fast, otherwise can slug；0.5h is stirred, stratification separates lower layer's organic phase, and upper strata aqueous phase is used
CH2Cl2It is extracted twice, 100g*2, merges organic phase；Organic phase uses 300g clear water, saturated sodium bicarbonate 200g, clear water respectively
300g is respectively washed once；By it is above-mentioned it is organic be added in cucurbit, major part CH are recycled in first 65 DEG C or so air-distillations2Cl2, then delay
Slow heating is finally distilled with water vacuum decompression until not having low-boiling point material at such a temperature until 90 DEG C；Terminate distillation, obtains
About 114g crude product, purity 93%, sterling yield 83.4%.
(2) synthesis (cyclization reaction) of 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one
Previous step vinasse 118g is added in 500ml four-hole bottle, 236g glacial acetic acid, the 11.8g concentrated sulfuric acid, temperature rising reflux is added
2h is reacted, sample detection is reaction end when not having previous step product.Water vacuum decompression is distilled to recover acetic acid, Zhi Daowen
Degree reaches 118-120 DEG C, does not have to stop distillation when acetic acid substantially；Liquid Residue is poured into 300g ice water, and 200g is added
CH2Cl2, stir 0.5h stratification；Separate lower layer's organic phase, upper strata aqueous phase CH2Cl2It is extracted twice, 50g*2, merges organic
Phase；Primary, clear water is washed with 5%NaOH 100g respectively and washes 150*2 twice, separates organic phase；Cucurbit is added to by organic above
In, CH is recycled in air-distillation2Cl2Until liquid temperature reaches 95 DEG C, pump distillation of changing oil obtains product 91.9g, purity 98%；Total recovery
81.39%。
Claims (9)
1. a kind of method of two-step method synthesis 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one, characterized in that
Include the following steps: that (1) under stirring, aluminum trichloride (anhydrous) is added into methylene chloride, different nonanoyl is successively added dropwise later
Chlorine and 3,3- methyl methacrylate, after completion of dropwise addition, heating reaction system to reflux is reacted, and reaction solution passes through after the completion
Cooling, stratification, separates lower layer's organic phase and upper strata aqueous phase, water phase is extracted, merges organic phase, and organic phase is washed, normal
Pressure distillation, the distillation of water vacuum decompression, finally it is thick to obtain 3,7,9,9- tetramethyl -2- decene -5- ketone acid methyl esters for collection vinasse
Product；(2) glacial acetic acid, the concentrated sulfuric acid, temperature rising reflux reaction are added in vinasse；Reaction solution is after the distillation of water vacuum decompression later
Methylene chloride stirring, stratification is added in cooling；Lower layer's organic phase is separated, merges organic phase, organic phase after extracting upper strata aqueous phase
Washed, air-distillation, oil pump distillation, obtain product.
2. two-step method synthesis 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one according to claim 1
Method, it is characterised in that: in step (1), the mass ratio of methylene chloride and aluminum trichloride (anhydrous) is 5:2, and the two is mixed
10min。
3. two-step method synthesis 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one according to claim 1
Method, it is characterised in that: in step (1), isononanoyl chloride and 3, the molar ratio of 3- methyl methacrylate is close to 1:1, and 3,3-
The micro- excess of methyl methacrylate；Isononanoyl chloride is slowly added dropwise at 25-30 DEG C, 0.5h is dripped off, heat preservation 10min is dripped off, it
3,3- methyl methacrylate is directly added dropwise afterwards, is to slowly warm up to 36-38 DEG C during being added dropwise, 1h is dripped.
4. two-step method synthesis 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one according to claim 1
Method, it is characterised in that: in step (1), heating reaction system to flowing back, examine by the back flow reaction 4-5h at 41-42 DEG C, sampling
It surveys, using no isononanoic acid as reaction end；Cooling reaction solution to 30 DEG C hereinafter, reaction solution is poured slowly into trash ice under stirring,
Stratification after stirring 0.5h, separates lower layer's organic phase.
5. two-step method synthesis 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one according to claim 1
Method, it is characterised in that: in step (1), the water phase separated is extracted with dichloromethane twice, merges organic phase, organic phase is successively
It respectively washed once with clear water, saturated sodium bicarbonate solution and clear water；By organic phase at 60-65 DEG C after air-distillation, slowly rise
Temperature carries out the distillation of water vacuum decompression to 90 DEG C at 90 DEG C, collects vinasse.
6. two-step method synthesis 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one according to claim 1
Method, it is characterised in that: in step (2), glacial acetic acid, the concentrated sulfuric acid are added in vinasse, temperature rising reflux reacts 2h, sampling inspection
It surveys, until no 3,7,9,9- tetramethyl -2- decene -5- ketone acid methyl esters are produced as reaction end.
7. two-step method synthesis 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one according to claim 1
Method, it is characterised in that: in step (2), water vacuum decompression is distilled to recover acetic acid, until temperature reaches 118-120 DEG C without acetic acid
When stop distillation；Liquid Residue is poured into ice water, and methylene chloride stirring, stratification is added；Separate lower layer's organic phase.
8. two-step method synthesis 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one according to claim 1
Method, it is characterised in that: in step (2), upper strata aqueous phase is extracted with dichloromethane twice, merges organic phase, and organic phase is used respectively
The sodium hydroxide solution of mass concentration 5% washed once, then be washed twice with clear water, separate organic phase；Organic phase is steamed through normal pressure
Recycling methylene chloride is evaporated, until liquid temperature is to 95 DEG C, pump distillation of changing oil obtains product.
9. two-step method synthesis 4- methyl -6- (2,4,4- tri-methyl-amyl) -2H- pyran-2-one according to claim 4
Method, it is characterised in that: the trash ice is the rubble ice containing concentrated hydrochloric acid, contains 100g concentrated hydrochloric acid in every 1200g rubble ice.
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