CN108774118A - A kind of preparation method of neotame key intermediate 3,3- dimethyl butyraldehydes - Google Patents
A kind of preparation method of neotame key intermediate 3,3- dimethyl butyraldehydes Download PDFInfo
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- CN108774118A CN108774118A CN201810736897.2A CN201810736897A CN108774118A CN 108774118 A CN108774118 A CN 108774118A CN 201810736897 A CN201810736897 A CN 201810736897A CN 108774118 A CN108774118 A CN 108774118A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—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
- C07C45/54—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 of compounds containing doubly bound oxygen atoms, e.g. esters
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
- C07C67/287—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by introduction of halogen; by substitution of halogen atoms by other halogen atoms
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Abstract
The present invention provides a kind of neotame key intermediate 3; the preparation method of 3- dimethyl butyraldehydes, in a reservoir, nitrogen protection; organic solvent and solid acid catalyst is added; tertiary butyl chloride is added dropwise, then aryl acids vinyl acetate is added dropwise, Filtration of catalyst after insulation reaction; organic layer is evaporated under reduced pressure; it adds alkali or acid is heated to reflux and hydrolyzes to obtain crude product, rectifying obtains 3,3- dimethyl butyraldehyde finished products to crude product again.Cost of material of the present invention is low, and reaction condition is mild, and side reaction easy to operate is few, safety and environmental protection, profit and industrialized production.
Description
Technical field
The invention belongs to the field of chemical synthesis, and in particular to a kind of neotame key intermediate 3, the preparation of 3- dimethyl butyraldehydes
Method.
Background technology
Neotame (Neotame) is a kind of novel non-nutritive high-potency sweetener, and by the Lars Niu Te, Vit develops it
Entitled N- [N-3,3- the dimethylbutyl]-L- ɑ of chemistry-lucid asparagus pacifies acyl]-L-phenylalanine 1- methyl esters, there is sugariness height, heat
It is low, it is the advantages that stability is good, safe to the human body harmless, there is huge market potential, and 3,3- dimethyl butyraldehydes are neotames
Important intermediate, since market volume is limited, so expensive, it is therefore desirable to study a novel synthetic method.
Disclosed synthesis 3,3- dimethyl butyraldehyde synthetic methods existing at present have：With isobutene in patent US6573409
Oxidizing process is closed by sour water to prepare 3,3- dimethyl aldehyde for raw material with ethylene, for this method to equipment requirement height, side reaction is more, production
Product purity is low.It is hydrolyzed and is prepared with 1,1-, bis- chloro- 3,3- bismethanes in patent US5994593, this method expensive starting materials are not easy to obtain
It takes.
Patent CN1301247A is disclosed with 3,3- dimethylbutyl chlorine as raw material, and cost of material price is high, and by-product is more,
It is also easy to produce secondary pollution, production cost is high, is not easy to carry out industrialized production.Patent CN102295541A is disclosed with a large amount of Louis
This sour alchlor is catalyst, and aftertreatment technology is cumbersome, and it is not disposable to generate a large amount of waste water.Patent US5856584 is disclosed
It is prepared using chloro- 3, the 3- dimethyl butyrates alkoxides of 1-, the disadvantages of this method is to make catalyst using iodide, expensive and bad
Recycling, and react and generate dimethyl disulfide ethers by-product, processing cost is high
Invention content
It is an object of the invention to overcome 3,3- dimethyl butyraldehydes synthetic method expensive starting materials, post-processing in the prior art multiple
It is miscellaneous, generate the defects of waste water is more, and provide a kind of simple for process, easy to operate, cost savings, the neotame of Environmental Safety is closed
The preparation method of key intermediate 3,3- dimethyl butyraldehydes.
The present invention provides a kind of neotame key intermediate 3, the preparation methods of 3- dimethyl butyraldehydes, it is characterised in that including
Following steps：
(1) Formula II compound is reacted with tertiary butyl chloride organic solvent system existing for solid acid, forms formula III
Close object；
Wherein R is C1~6Alkyl, phenyl or R are substituted-phenyl；The substituted-phenyl refers to by one or more halogens, C1~6
Alkyl or the phenyl of nitro substitution；
(2) formula III compound hydrolysis is obtained into 3,3- dimethyl butyraldehydes；
The same step of definition (1) of R group in step (2).
Inventor has found, when R is phenyl or R is substituted-phenyl, the yields of 3,3- dimethyl butyraldehydes is C compared with R1~6Alkyl
When have further promotion.
Preferably, organic solvent is the aromatic hydrocarbons or C replaced by one or more halogens in the step (1)1~10Alkane.
Preferably, solid acid can be the AlCl of support type in the step (1)3, support type solid strong acid or solid it is super
One or several kinds in strong acid.
Preferably, the weight ratio of solid acid and Formula II compound is 0.05 in the step (1):1~0.5:1；Further
, the weight ratio of solid acid and Formula II compound is 0.1 in the step (1):1~0.2:1.
Preferably, the molar ratio of tertiary butyl chloride and Formula II compound is 1.5 in the step (1):1~1.0:1；It is preferred that
, the molar ratio of tertiary butyl chloride and Formula II compound is 1.5 in the step (1):1~1.2:1.
Preferably, in the step (1) when adding type II compounds and tertiary butyl chloride, in reaction system temperature be maintained at-
15 DEG C~0 DEG C；When adding type II compounds are with tertiary butyl chloride in the further step (1), temperature is kept in reaction system
At -10 DEG C~-5 DEG C.
Preferably, hydrolysis uses acid catalysis or base catalysis in the step (2).
Preferably, hydrolysising reacting temperature is controlled at 50 DEG C~150 DEG C in the step (2)；Reaction time is 0.5~20h；
Further, hydrolysising reacting temperature is controlled at 80 DEG C~120 DEG C in the step (2)；Reaction time is 2~10h.
Preferably, when the step (2) uses acid catalysis, used acid is inorganic acid or organic acid.The wherein described nothing
Machine acid includes hydrochloric acid, sulfuric acid, phosphoric acid etc., and organic acid includes carboxylic acid and sulfonic acid, for example, trifluoroacetic acid, acetic acid, methanesulfonic acid, to toluene
Sulfonic acid etc..
Preferably, when the step (2) uses base catalysis, used alkali is alkali metal hydroxide；Such as hydroxide
Sodium, potassium hydroxide, lithium hydroxide or cesium hydroxide.
The beneficial effects of the invention are as follows：The present invention provides the method low raw-material cost of synthesis 3,3- dimethyl butyraldehydes, instead
Mild condition is answered, it is easy to operate, reaction impurities are reduced, crude product and finished product yield, 3, the 3- dimethyl butyraldehyde purity of preparation are improved
Height, safety and environmental protection, profit and industrialized production, prospect of production are good.
Specific implementation mode
Illustrate technical scheme of the present invention below by way of specific embodiment, but the scope of the present invention is not limited thereto.
The name of compound Chinese and chemical structural formula have conflict in the present invention, are subject to chemical structural formula.
Embodiment 1
In a 2500ml four-hole boiling flask, thermometer, nitrogen be sufficiently displaced from protection after input 400.0g dichloromethane and
20.0g solid AlCl3/Al2O3, -10 DEG C are cooled to, 203.6g tertiary butyl chlorides (2.2mol) are then slowly added dropwise, are dripped in 1 hour
Add it is complete, then start be added dropwise 200g vinyl propionates (2mol), rear insulation reaction is added dropwise in 1 hour 2 hours, cross filter out
Go catalyst, catalyst recycling.Then organic layer is evaporated under reduced pressure removal low-boiling point material and obtains intermediate, added in intermediate
Enter 700g NaOH (15%) aqueous solution, crude product 3,3- dimethyl butyrates are obtained after being heated to 110 DEG C of 10 small layereds of back hydrolysis
Aldehyde, crude product obtain 3, the 3- dimethyl butyraldehydes that purity is 99.0%, yield 80% by rectifying.
Embodiment 2
In a 2500ml four-hole boiling flask, thermometer, nitrogen be sufficiently displaced from protection after input 400.0g dichloroethanes and
59.0g solid TiO2/SO4 2-, -8 DEG C are cooled to, 185.1g tertiary butyl chlorides (2mol) are then slowly added dropwise, are dripped in 1 hour
Finish, then starts that 444.5g vinyl benzoates (3mol) are added dropwise, rear insulation reaction is added dropwise in 1 hour 2 hours, cross and filter out
Go catalyst, catalyst recycling.Then organic layer is evaporated under reduced pressure removal low-boiling point material and obtains intermediate, added in intermediate
Enter after 2.0g catalyst amberlyst35 and 200.0g deionized waters are heated to the filtration catalytic agent in 2 hours of 90 DEG C of back hydrolysis, point
Layer obtains crude product 3,3- dimethyl butyraldehydes, and crude product obtains 3, the 3- dimethyl butyraldehydes that purity is 99.2%, yield by rectifying
86%.
Embodiment 3
In a 2500ml four-hole boiling flask, thermometer, nitrogen be sufficiently displaced from protection after input 400.0g dichloroethanes and
59.0g solid AlCl3/Al2O3, -8 DEG C are cooled to, 185.1g tertiary butyl chlorides (2mol) are then slowly added dropwise, are dripped in 1 hour
Finish, then start that 547.8g 2- chlorobenzoic acids vinyl acetates (3mol) are added dropwise, rear insulation reaction is added dropwise in 1 hour 2 hours,
Filtration of catalyst, catalyst recycling.Then organic layer is evaporated under reduced pressure removal low-boiling point material and obtains intermediate, in centre
2.0g catalyst amberlyst35 and 200.0g deionized waters are added in body and are heated to 90 DEG C of back hydrolysis, 2 hours filtration catalytics
After agent, layering obtains crude product 3,3- dimethyl butyraldehydes, and crude product obtains 3, the 3- dimethyl butyraldehydes that purity is 99.1% by rectifying,
Yield 88%.
It is enlightenment with above-mentioned desirable embodiment according to the present invention, through the above description, relevant staff is complete
Various changes and amendments can be carried out without departing from the scope of the technological thought of the present invention' entirely.The technology of this invention
Property range is not limited to the contents of the specification, it is necessary to determine its technical scope according to right.
Claims (10)
1. a kind of neotame key intermediate 3, the preparation method of 3- dimethyl butyraldehydes, it is characterised in that include the following steps：
(1) Formula II compound is reacted with tertiary butyl chloride organic solvent system existing for solid acid, forms formula III chemical combination
Object；
Wherein R is phenyl or R is substituted-phenyl；The substituted-phenyl refers to by one or more halogens, C1~6Alkyl or nitro substitution
Phenyl；
(2) formula III compound hydrolysis is obtained into 3,3- dimethyl butyraldehydes；
2. the preparation method of 3,3- dimethyl butyraldehydes as described in claim 1, it is characterised in that organic molten in the step (1)
Agent is by aromatic hydrocarbons that one or more halogens replace or the C replaced by one or more halogens1~10Alkane.
3. the preparation method of 3,3- dimethyl butyraldehydes as described in claim 1, which is characterized in that solid in the step (1)
Acid can be the AlCl of support type3, support type solid strong acid or the one or several kinds in solid super-strong acid.
4. the preparation method of 3,3- dimethyl butyraldehydes as claimed in claim 3, which is characterized in that solid in the step (1)
The weight ratio of acid and Formula II compound is 0.05:1~0.5:1.
5. the preparation method of 3,3- dimethyl butyraldehydes as described in claim 1, which is characterized in that tertiary fourth in the step (1)
The molar ratio of base chlorine and Formula II compound is 1.5:1~1.0:1.
6. the preparation method of 3,3- dimethyl butyraldehydes as claimed in claim 5, which is characterized in that addition in the step (1)
When Formula II compound is with tertiary butyl chloride, temperature is maintained at -15 DEG C~0 DEG C in reaction system.
7. the preparation method of 3,3- dimethyl butyraldehydes as described in claim 1, which is characterized in that hydrolysis in the step (2)
Reaction uses acid catalysis or base catalysis.
8. the preparation method of 3,3- dimethyl butyraldehydes as claimed in claim 7, which is characterized in that hydrolysis in the step (2)
Reaction temperature is controlled at 50 DEG C -150 DEG C；Reaction time is 0.5~20h.
9. the preparation method of 3,3- dimethyl butyraldehydes as claimed in claim 7, which is characterized in that the step (2) is using acid
When catalysis, used acid is inorganic acid, organic acid or sulfonic acid.
10. the preparation method of 3,3- dimethyl butyraldehydes as claimed in claim 7, which is characterized in that the step (2) uses alkali
When catalysis, used alkali is alkali metal hydroxide.
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Citations (5)
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|---|---|---|---|---|
| CN1360563A (en) * | 1999-07-02 | 2002-07-24 | 纳特拉斯维特公司 | Process for preparation of 3,3-dimethylbutanal |
| CN102295541A (en) * | 2011-08-16 | 2011-12-28 | 济南诚汇双达化工有限公司 | Preparation method of 3,3-dimethyl butyraldehyde |
| CN104045688A (en) * | 2014-06-18 | 2014-09-17 | 济南诚汇双达化工有限公司 | Synthetic method of neotame |
| CN104130115A (en) * | 2014-08-20 | 2014-11-05 | 山东奔月生物科技有限公司 | Method for preparing 3,3-dimethyl butyraldehyde |
| CN104817442A (en) * | 2015-03-12 | 2015-08-05 | 青岛诚汇双达生物科技有限公司 | Preparation method for 3, 3-dimethylbutyraldehyde |
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2018
- 2018-07-06 CN CN201810736897.2A patent/CN108774118A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1360563A (en) * | 1999-07-02 | 2002-07-24 | 纳特拉斯维特公司 | Process for preparation of 3,3-dimethylbutanal |
| CN102249851A (en) * | 1999-07-02 | 2011-11-23 | 纳特拉斯维特公司 | Process for the preparation of 3,3-dimethylbutanal |
| CN102295541A (en) * | 2011-08-16 | 2011-12-28 | 济南诚汇双达化工有限公司 | Preparation method of 3,3-dimethyl butyraldehyde |
| CN104045688A (en) * | 2014-06-18 | 2014-09-17 | 济南诚汇双达化工有限公司 | Synthetic method of neotame |
| CN104130115A (en) * | 2014-08-20 | 2014-11-05 | 山东奔月生物科技有限公司 | Method for preparing 3,3-dimethyl butyraldehyde |
| CN104817442A (en) * | 2015-03-12 | 2015-08-05 | 青岛诚汇双达生物科技有限公司 | Preparation method for 3, 3-dimethylbutyraldehyde |
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