CN109160875A - A kind of sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde and preparation method thereof - Google Patents
A kind of sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde and preparation method thereof Download PDFInfo
- Publication number
- CN109160875A CN109160875A CN201810889815.8A CN201810889815A CN109160875A CN 109160875 A CN109160875 A CN 109160875A CN 201810889815 A CN201810889815 A CN 201810889815A CN 109160875 A CN109160875 A CN 109160875A
- Authority
- CN
- China
- Prior art keywords
- hydroxyl
- sweetener
- methoxyl group
- preparation
- cinnamaldehyde
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
- C07C45/74—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups combined with dehydration
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/20—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms
- C07C47/277—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Seasonings (AREA)
Abstract
The invention discloses a kind of sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehydes and preparation method thereof.This method step are as follows: highly basic and 3- hydroxyl -4-methoxybenzaldehyde are dissolved in the water, stirs to being completely dissolved, is transferred in the double-layer glass reaction kettle for being cooled to required temperature in advance；Acetaldehyde solution is added dropwise, continues to stir after being added dropwise to complete, concentrated hydrochloric acid is added dropwise thereto and terminates reaction, filtering reacting liquid, rotary evaporation is freeze-dried to obtain faint yellow solid；Faint yellow solid is dissolved in methanol aqueous solution, then stirring to solid is completely dissolved in water bath with thermostatic control；It takes supernatant, stands cooling, gained crystal is filtered, and after being washed with distilled water for several times, vacuum drying obtains crystal.Reaction raw materials of the present invention are easy to get, simple process, improve Advantame intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde synthesis technology, and yield reaches as high as 65% or more, and purity reaches as high as 85% or more.
Description
Technical field
The invention belongs to food chemistry technical fields, and in particular to a kind of high sweetener Advantame intermediate 3- hydroxyl
Base -4- methoxyl group-cinnamaldehyde preparation method.
Background technique
Sweetener is an important branch of food additives, it can improve the mouthfeel of food, and enhancing flavour of food products is simultaneously full
Sufficient edible property, some can also to play certain disease prevention and therapeutic effect, it has also become can not in public daily life
Or a kind of scarce flavouring.Wherein, sucrose is the main sweet taste ingredient of food industry, has in good taste, lower-price characteristic,
But since its heat is big, metabolism needs insulin, and rear taste turns sour, and is to lead to saprodontia, obesity, heart disease, diabetes and cancer
Etc. one of the root of diseases, sucrose Excess free enthalpy is identified as being an important unhealthy factor.And functional sweetener can
It is applied in food instead of sucrose, and there is special physiological function, be not only able to satisfy people to the preference of sweet food, but also will not cause
Side effect can reduce the diseases probability of happening such as obesity and hyperlipidemia, and have certain adjuvant treatment to diabetes, hepatopath
Effect.Therefore make great efforts the high sugariness of development and production, functional sweetener low in calories, to meet food development and adjustment of diet
Needs, be the trend of domestic and international Development of Food Additives in China.
Advantame is a kind of derivative of Aspartame, and chemical structure is similar with neotame, is a kind of non-nutritive low
The perceptual intensity of the new type functional sweetener of calorific value high intensity, bitter taste and tart flavour is extremely faint, good water solubility, heat resisting temperature
Height, being suitable for high temperature process product can make an addition in numerous food as sweetener and flavoring agent, sugariness up to the 20 of sucrose,
000 times, be the highest sugariness substance of human development so far.Its entitled N-(N-(3-(3- hydroxyl -4- methoxyphenyl of chemistry) third
Base-L-a- aspartoyl)-L-phenylalanine -1- methyl esters (C24H30N2O7·H2O), molecular weight 476.52.
Japanese aginomoto has studied the Aspartame that the 3- phenyl propane derivative on phenyl ring with various substituent groups replaces
Derivative has obtained the Aspartame derivative that a large amount of sugarinesses sugarinesses suitable or even certain with neotame are much larger than neotame.Yan An
Deng the method that (food industry science and technology, 32 (8): 336-339,2011) combine successfully synthesizing neotame, by with cinnamic acid and Ah
Aspartame derivative is made through reductive alkylation for raw material in this Ba Tian, to the Aspartame derivative for synthesizing higher sugariness
Method and technique lay the foundation.Japanese riverhead hereby et al. (Japan Patent JP:01809302.7) using conventional method of peptide synthesis
Advantame is synthesized, but process flow is long, to be allowed to realize that industrialized production is also had any problem.Then, look for another way herein,
The suitable and cheap aldehydes of one kind is found as starting material to synthesize Advantame by two-step reaction, industrialize for it
Process ba- sis has been established in production.
Summary of the invention
The purpose of the present invention is to provide a kind of completely new Advantame intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehydes
Preparation method, solve the disadvantage that the prior art and deficiency.The present invention, which selects, has the electron-donating groups such as hydroxyl or methoxyl group
Benzaldehyde derivative and acetaldehyde are raw material, and single step reaction is only needed to obtain Advantame intermediate 3- hydroxyl -4- first through aldol condensation
Oxygroup-cinnamaldehyde.So that reaction is eased, convenient for operation, it is suitable for industrialization amplification.
The object of the invention is achieved through the following technical solutions:
A kind of preparation method of sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde, includes the following steps:
(1) highly basic and 3- hydroxyl -4-methoxybenzaldehyde are dissolved in the water, stir to being completely dissolved, is transferred to and is cooled in advance
In the double-layer glass reaction kettle of required temperature；
(2) acetaldehyde solution is added dropwise, continues to stir after being added dropwise to complete, concentrated hydrochloric acid is added dropwise thereto and terminates and reacts, filtering reacting liquid,
Rotary evaporation is freeze-dried to obtain faint yellow solid；
(3) faint yellow solid is dissolved in methanol aqueous solution, then stirring to solid is completely dissolved in water bath with thermostatic control；
(4) it takes supernatant, stands cooling, gained crystal is filtered, and after being washed with distilled water for several times, vacuum drying obtains crystalline substance
Body.
In the above method, the highly basic is sodium hydroxide；The highly basic additional amount is 3- hydroxyl -4-methoxybenzaldehyde matter
1 ~ 3 times of amount.
In the above method, the dripping quantity of the acetaldehyde solution is 2 ~ 5 times of 3- hydroxyl -4-methoxybenzaldehyde quality；
The acetaldehyde mass fraction is 25% ~ 30%；The acetaldehyde time for adding is 2 ~ 4h.
In the above method, the temperature of the reaction is -10 ~ 0 DEG C.
In the above method, the adjusting pH, which refers to, adjusts pH to 7.0 ~ 8.0 with concentrated hydrochloric acid.
In the above method, the methanol aqueous solution mass fraction is 30% ~ 60%.
In the above method, the standing cooling temperature is -10 ~ 10 DEG C；The standing cooling time is 10 ~ 18h.
A kind of lane sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde, to sweetener intermediate weight percent
Meter, the sweetener intermediate yield are 60% ~ 65%, and purity is 85% ~ 90%.
Preparation method of the invention and obtained product, have the following advantages that and the utility model has the advantages that
(1) method according to the present invention finds that the manufacturing method of the intermediate exists compared with the manufacture route of front complexity
It is excellent in technique；
(2) the resulting Advantame intermediate of the present invention, yield and purity are higher；
(3) raw material used in the present invention is cheap and easy to get.
Detailed description of the invention
Fig. 1 is process flow chart of the invention.
Specific embodiment
Below with reference to embodiment, the present invention is described in further detail, and embodiments of the present invention are not limited thereto.
Embodiment 1
(1) sodium hydroxide (64g, 1.6 mol) and 3- hydroxyl -4-methoxybenzaldehyde (24.24g, 0.16 mol) are dissolved in
In 400 mL water, sodium hydroxide and 3- hydroxyl -4-methoxybenzaldehyde mass ratio are 2.64:1 at this time, are stirred to completely molten
Solution, is transferred in the double-layer glass reaction kettle for being cooled to -5 DEG C in advance.
(2) slowly continuous into this aqueous slkali in 4h that 28% acetaldehyde solution (48.48g, 0.368 mol) is added dropwise, this
When acetaldehyde solution and 3- hydroxyl -4-methoxybenzaldehyde mass ratio be 2:1, continue after being added dropwise to complete stir 2h, thereto
Concentrated hydrochloric acid is added dropwise and adjusts pH to 7.0 and terminates and reacts, filtering reacting liquid, rotary evaporation is freeze-dried to obtain faint yellow solid
32.23g。
(3) faint yellow solid is dissolved in 200 mL, in 50% methanol aqueous solution, is then stirred in 40 DEG C of waters bath with thermostatic control
It mixes to solid and is completely dissolved.
(4) supernatant is only taken if having insoluble impurity, and cooling 12h is stood at 5 DEG C.Gained crystal is filtered under diminished pressure, is used in combination
After distilling water washing for several times, vacuum drying obtains crystal 18.36g.To sweetener intermediate percent by weight, sweetener
Intermediate yield is 64.46%, is 91.78% through HPLC detection purity.
2 the present embodiment of embodiment difference from example 1 is that:
Double-layer glass reaction kettle precooling temperature in step (1) is adjusted to -10 DEG C；By acetaldehyde solution quality in step (2) point
Number is adjusted to 25%；Acetaldehyde solution additive amount is adjusted to (121.2g, 0.689 mol), at this time acetaldehyde solution and 3- hydroxyl-
The mass ratio of 4-methoxybenzaldehyde is 5:1；Methanol aqueous solution mass fraction in step (3) is adjusted to 30%；By step (4)
Middle standing cooling temperature is adjusted to 0 DEG C.
By calculating, with to sweetener intermediate percent by weight, sweetener intermediate yield is 62.07%, through HPLC
Detecting purity is 90.75%.
3 the present embodiment of embodiment difference from example 1 is that:
Sodium hydroxide additive amount in step (1) is adjusted to (48.48g, 1.212 mol), at this time sodium hydroxide and 3- hydroxyl-
The mass ratio of 4-methoxybenzaldehyde is 2:1, and double-layer glass reaction kettle precooling temperature is adjusted to 0 DEG C；By acetaldehyde water in step (2)
Liquid quality fraction is adjusted to 30%, and acetaldehyde time for adding is adjusted to 3h, at this time acetaldehyde solution and 3- hydroxyl -4- methoxybenzene
The mass ratio of formaldehyde is 2:1, and pH is adjusted to 8.0；Methanol aqueous solution mass fraction is adjusted to 60% in step (3)；By step (4)
Middle standing is adjusted to 18h cooling time.
By calculating, with to sweetener intermediate percent by weight, sweetener intermediate yield is 62.57%, through HPLC
Detecting purity is 85.67%.
4 the present embodiment of embodiment difference from example 1 is that:
Sodium hydroxide additive amount in step (1) is adjusted to (24.24g, 0.61 mol), at this time sodium hydroxide and 3- hydroxyl -4-
The mass ratio of methoxybenzaldehyde is 1:1, and double-layer glass reaction kettle precooling temperature is adjusted to -10 DEG C；Acetaldehyde in step (2) is dripped
2h is adjusted between added-time, acetaldehyde solution additive amount is adjusted to (72g, 0.458 mol), at this time acetaldehyde solution and 3- hydroxyl-
The mass ratio of 4-methoxybenzaldehyde is 2.97:1；Methanol aqueous solution mass fraction is adjusted to 60% in step (3)；By step (4)
Middle standing cooling temperature is adjusted to -10 DEG C.
By calculating, with to sweetener intermediate percent by weight, sweetener intermediate yield is 62.57%, through HPLC
Detecting purity is 85.67%.
5 the present embodiment of embodiment difference from example 1 is that:
Sodium hydroxide additive amount in step (1) is adjusted to (72.72g, 1.818 mol), at this time sodium hydroxide and 3- hydroxyl -4-
The mass ratio of methoxybenzaldehyde is 3:1；Acetaldehyde solution mass fraction in step (2) is adjusted to 25%, acetaldehyde is water-soluble at this time
Liquid and 3- hydroxyl -4-methoxybenzaldehyde mass ratio are 2:1, and pH is adjusted to 7.5；Methanol aqueous solution quality point in step (3)
Number is adjusted to 60%；10 DEG C are adjusted to by cooling temperature is stood in step (4), cooling time is stood and is adjusted to 10h.
By calculating, with to sweetener intermediate percent by weight, sweetener intermediate yield is 62.57%, through HPLC
Detecting purity is 85.67%.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention,
It should be equivalent substitute mode, be included within the scope of the present invention.
Claims (9)
1. a kind of preparation method of sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde, which is characterized in that including following
Step:
(1) highly basic and 3- hydroxyl -4-methoxybenzaldehyde are dissolved in the water, stir to being completely dissolved, is transferred to and is cooled in advance
In the double-layer glass reaction kettle of required temperature；
(2) acetaldehyde solution is added dropwise, continues to stir after being added dropwise to complete, concentrated hydrochloric acid is added dropwise thereto and terminates and reacts, filtering reacting liquid,
Rotary evaporation is freeze-dried to obtain faint yellow solid；
(3) faint yellow solid is dissolved in methanol aqueous solution, then stirring to solid is completely dissolved in water bath with thermostatic control；
(4) it takes supernatant, stands cooling, gained crystal is filtered, and after being washed with distilled water for several times, vacuum drying obtains crystalline substance
Body.
2. a kind of preparation method of sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde according to claim 1,
It is characterized by: the highly basic is sodium hydroxide；The highly basic additional amount is 3- hydroxyl -4-methoxybenzaldehyde quality 1 ~ 3
Times.
3. a kind of preparation method of sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde according to claim 1,
It is characterized by: the dripping quantity of the acetaldehyde solution is 2 ~ 5 times of 3- hydroxyl -4-methoxybenzaldehyde quality；The acetaldehyde
Mass fraction is 25% ~ 30%；The acetaldehyde time for adding is 2 ~ 4h.
4. a kind of preparation method of sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde according to claim 1,
It is characterized by: the temperature of the reaction is -10 ~ 0 DEG C.
5. a kind of preparation method of sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde according to claim 1,
It is characterized by: the adjusting pH, which refers to, adjusts pH to 7.0 ~ 8.0 with concentrated hydrochloric acid.
6. a kind of preparation method of sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde according to claim 1,
It is characterized by: the methanol aqueous solution mass fraction is 30% ~ 60%.
7. a kind of preparation method of sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde according to claim 1,
It is characterized by: the standing cooling temperature is -10 ~ 10 DEG C；The standing cooling time is 10 ~ 18h.
8. sweetener intermediate 3- hydroxyl -4- methoxyl group-phenylpropyl alcohol is prepared by any one of claim 1 ~ 8 preparation method
Olefine aldehydr.
9. sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde according to claim 8, which is characterized in that sweet tea
Taste agent intermediate percent by weight, the sweetener intermediate yield are 60% ~ 65%, and purity is 85% ~ 90%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810889815.8A CN109160875A (en) | 2018-08-07 | 2018-08-07 | A kind of sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810889815.8A CN109160875A (en) | 2018-08-07 | 2018-08-07 | A kind of sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109160875A true CN109160875A (en) | 2019-01-08 |
Family
ID=64895214
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810889815.8A Pending CN109160875A (en) | 2018-08-07 | 2018-08-07 | A kind of sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109160875A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1429193A (en) * | 2000-05-16 | 2003-07-09 | 味之素株式会社 | Process for producing cinnamylaldehyde derivatives, use thereof and the like |
| CN102992981A (en) * | 2012-12-24 | 2013-03-27 | 湖北远成药业有限公司 | Industrial preparation method of 3-methoxycinnamaldehyde |
| CN107556182A (en) * | 2017-10-17 | 2018-01-09 | 厦门大学 | The preparation method of the methoxycinnamic aldehyde of 3 hydroxyl 4 |
-
2018
- 2018-08-07 CN CN201810889815.8A patent/CN109160875A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1429193A (en) * | 2000-05-16 | 2003-07-09 | 味之素株式会社 | Process for producing cinnamylaldehyde derivatives, use thereof and the like |
| CN102992981A (en) * | 2012-12-24 | 2013-03-27 | 湖北远成药业有限公司 | Industrial preparation method of 3-methoxycinnamaldehyde |
| CN107556182A (en) * | 2017-10-17 | 2018-01-09 | 厦门大学 | The preparation method of the methoxycinnamic aldehyde of 3 hydroxyl 4 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7141263B2 (en) | Process for producing cinnamaldehyde derivatives, use thereof and the like | |
| JP2018526431A (en) | Rebaudioside D crystal form A, process for its production and use thereof | |
| FI58489B (en) | ETH SOETNINGSMEDEL INNEHAOLLANDE 1- (2-HYDROXI-4-CARBOXIMETOXYFENYL) -3- (3-HYDROXI-4-METHOXYPHENYL) PROPAN-1-ON OCH / ELLER DESS ALKALI METAL SALTER | |
| CN109988132B (en) | Preparation method of amiodarone hydrochloride | |
| US20200010497A1 (en) | Stevioside m crystal form, preparation method therefor and use thereof | |
| CN110041215A (en) | A kind of preparation method of food-grade glycine zine chelate | |
| CN105801636A (en) | Synthetic method for naringin dihydrochalcone | |
| CN109160875A (en) | A kind of sweetener intermediate 3- hydroxyl -4- methoxyl group-cinnamaldehyde and preparation method thereof | |
| WO2009062659A2 (en) | Polymorphs of enantiopure erdosteine | |
| CN112321552A (en) | Synthesis method of delta-caprolactone spice | |
| CN110950747A (en) | Synthesis method of hesperetin dihydrochalcone | |
| WO2019178947A1 (en) | Preparation method for azoxystrobin and intermediate thereof | |
| CN101735037A (en) | Synthesis method of sweet taste inhibitor 2-(4- methoxyphenyl) sodium propionate | |
| CN106543119B (en) | A kind of preparation method of optical voidness Ta Simeiqiong | |
| CN101434533B (en) | Novel preparation of sofalcone | |
| CN108329364A (en) | A method of preparing sweetener based on Exocarpium Citri Grandis | |
| CN110551011A (en) | synthesis method of hesperetin dihydrochalcone | |
| CN105061327A (en) | Synthetic method of long-acting sulfonamide | |
| CN108892645A (en) | A method of preparing Tetramethylpyrazine | |
| KR101123609B1 (en) | Tetrahydroxycinnamate and tetrahydroxyamide derivatives, preparation method thereof and external application composition for skin whitening comprising same | |
| CN112876354A (en) | 2- (4-methoxyphenoxy) propionic acid derivative with sweet taste inhibiting effect and industrial production method thereof | |
| CN101492388A (en) | Method for synthesis of Miqujing medicament material | |
| CN101538217B (en) | Novel synthesis method and intermediate for 2-ethoxy-4-amino-5-chlorobenzoic acid | |
| CN113861047B (en) | Synthesis method of 2- (2-methoxyphenoxy) ethylamine | |
| CN101270092B (en) | Method for synthesizing neotame |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190108 |