CN105418443A - Method for synthesizing left-handed p-hydroxyphenyl glycine - Google Patents
Method for synthesizing left-handed p-hydroxyphenyl glycine Download PDFInfo
- Publication number
- CN105418443A CN105418443A CN201510760169.1A CN201510760169A CN105418443A CN 105418443 A CN105418443 A CN 105418443A CN 201510760169 A CN201510760169 A CN 201510760169A CN 105418443 A CN105418443 A CN 105418443A
- Authority
- CN
- China
- Prior art keywords
- hpg
- resolving agent
- handed
- hydroxyphenyl glycine
- synthesis
- 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
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/30—Preparation of optical isomers
- C07C227/34—Preparation of optical isomers by separation of optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for synthesizing left-handed p-hydroxyphenyl glycine. According to the method, mixing-handed p-hydroxyphenyl glycine is taken as a raw material, drinking water is taken as solvent, and D-3-bromine camphorsulfonic acid is taken as a resolving agent. The method comprises the following steps that 1, the mixing-handed p-hydroxyphenyl glycine is heated and dissolved in the drinking water, then the resolving agent is added, and mixing is performed for a reaction to obtain double salt prepared from the mixing-handed p-hydroxyphenyl glycine and the resolving agent; 2, the double salt prepared form the mixing-handed p-hydroxyphenyl glycine and the resolving agent is dissolved in water and then mixed with alkali liquor, and the left-handed p-hydroxyphenyl glycine is obtained through stirring crystallizing, separating, washing and drying. The method has the advantages that the conversion rate of the mixing-handed p-hydroxyphenyl glycine to the left-handed p-hydroxyphenyl glycine can reach 99.9%, the unit consumption of the resolving agent can reach 0.023-0.025, optical rotation of the left-handed p-hydroxyphenyl glycine can reach minus 158 degrees-160 degrees, no right-handed p-hydroxyphenyl glycine is detected out, the product quality is high, and the international enterprise requirements are totally met.
Description
Technical field
The invention belongs to technical field of compound preparation, particularly relate to a kind of method of synthesizing D-HPG.
Background technology
D-HPG (write a Chinese character in simplified form and make D-p-HPG) is a kind of outward appearance is white crystalline powder, fusing point is 225 ~ 227 DEG C, content >=98.5%, specific rotatory power is-155 ~-161 °, and D-HPG and deep processed product Deng Shi sylvite thereof are the necessary main side chain intermediates of synthesizing efficient broad-spectrum antimicrobial class medicine.
Domestic and foreign literature report mainly contain following several synthetic method: 1, namely Strecker Amino acid synthesis uses acidic hydrolysis after p-Hydroxybenzaldehyde and prussiate effect; 2, ammonia solution after hydroxymandelic acid is made in oxoethanoic acid and phenol effect; 3, oxoethanoic acid and urea, phenol effect are made 4-Hydroxyphenyl hydantoin and are hydrolyzed; 4, oxoethanoic acid and phenol, ammonium salt effect directly generate target compound.At present; the most frequently used industrializing synthesis route take p-Hydroxybenzaldehyde as raw material; react in alcohol solvent with sodium cyanide, bicarbonate of ammonia, volatile salt or ammonium chloride; generate DL-4-Hydroxyphenyl hydantoin; use sodium hydroxide hydrolysis again; acidifying, obtains DL-HPG methyl esters in esterification, and after splitting with D-tartrate, hydrolysis obtains product; this method technical maturity; shortcoming uses highly toxic substance sodium cyanide, needs strictly to control, not so very easily security incident occurs; in addition; quality product is poor, and Material Cost is high, is unfavorable for the large-scale production of enterprise.
Summary of the invention
In order to overcome the defect of prior art, the object of the present invention is to provide a kind of method of synthesizing D-HPG, improve each reactions steps yield, reduce energy consumption and Material Cost, obtained high quality meets the D-HPG of international corporation requirement.
The method of synthesis D-HPG, be characterized in taking racemic para hydroxybenzene glycine as raw material, tap water is solvent, D-3-bromo-camphor sulfonic acid is resolving agent, the method comprises the following steps: 1) dissolve in tap water by racemic para hydroxybenzene glycine heating, then resolving agent is added, hybrid reaction, obtains the double salt that D-HPG and resolving agent are formed; 2) double salt D-HPG and resolving agent formed is soluble in water, then mixes with alkali lye, through stirring and crystallizing, is separated, and washing drying obtains D-HPG.
Preferably, described racemic para hydroxybenzene glycine dissolves in the temperature of tap water is 70 ~ 100 DEG C.
Preferably, the time of described hybrid reaction is 2 ~ 6h.
Preferably, the mass ratio of the double salt that formed of described D-HPG and resolving agent and water is 1:(1 ~ 3).
Preferably, described alkali lye is one or more mixing solutionss in ammoniacal liquor, sodium hydroxide solution or potassium hydroxide solution.
Preferably, the pH value of the mixing solutions obtained after mixing with alkali lye is 6 ~ 8, and optimal ph is 7.
Racemic para hydroxybenzene glycine for resolving agent with D-3-bromo-camphor sulfonic acid, splits, obtains D-HPG by the present invention.Synthesis technique of the present invention is simple, easy to operate, resolving agent low price used, D-HPG productive rate is high, and resolving agent unit consumption is low, racemic para hydroxybenzene glycine can reach 99.9% to D-HPG transformation efficiency, resolving agent unit consumption can reach 0.023 ~ 0.025, and D-HPG optically-active can reach-158 ~-160 °, and does not detect dextrorotation D-pHPG, quality product is high, meets international corporation requirement completely.
Embodiment
Below in conjunction with embodiment to the present invention's row detailed description further.
Embodiment 1
The method of synthesis D-HPG, take racemic para hydroxybenzene glycine as raw material, tap water is solvent, D-3-bromo-camphor sulfonic acid is resolving agent, the method comprises the following steps: 1) racemic para hydroxybenzene glycine being dissolved in Heating temperature is in 80 DEG C of tap water, then resolving agent is added, hybrid reaction 2h, obtains the double salt that D-HPG and resolving agent are formed; 2) mass ratio of the double salt that formed of D-HPG and resolving agent and water is 1:1, double salt D-HPG and resolving agent formed is soluble in water, mix with 20% ammoniacal liquor again, pH value controls about 7, through stirring and crystallizing, be separated, washing drying obtains D-HPG.
The transformation efficiency of the racemic para hydroxybenzene glycine of the present embodiment is in table 1.
Embodiment 2
The method of synthesis D-HPG, take racemic para hydroxybenzene glycine as raw material, tap water is solvent, D-3-bromo-camphor sulfonic acid is resolving agent, the method comprises the following steps: 1) racemic para hydroxybenzene glycine being dissolved in Heating temperature is in 85 DEG C of tap water, then resolving agent is added, hybrid reaction 4h, obtains the double salt that D-HPG and resolving agent are formed; 2) mass ratio of the double salt that formed of D-HPG and resolving agent and water is 1:3, double salt D-HPG and resolving agent formed is soluble in water, mix with 20% sodium hydroxide solution again, pH value controls about 8, through stirring and crystallizing, be separated, washing drying obtains D-HPG.
The transformation efficiency of the racemic para hydroxybenzene glycine of the present embodiment is in table 1.
Embodiment 3
The method of synthesis D-HPG, take racemic para hydroxybenzene glycine as raw material, tap water is solvent, D-3-bromo-camphor sulfonic acid is resolving agent, the method comprises the following steps: 1) racemic para hydroxybenzene glycine being dissolved in Heating temperature is in 90 DEG C of tap water, then resolving agent is added, hybrid reaction 3h, obtains the double salt that D-HPG and resolving agent are formed; 2) mass ratio of the double salt that formed of D-HPG and resolving agent and water is 1:2, double salt D-HPG and resolving agent formed is soluble in water, mix with the mixing solutions of 20% ammoniacal liquor with 20% potassium hydroxide solution again, pH value controls about 6, through stirring and crystallizing, be separated, washing drying obtains D-HPG.
The transformation efficiency of the racemic para hydroxybenzene glycine of the present embodiment is in table 1.
Embodiment 4
The method of synthesis D-HPG, take racemic para hydroxybenzene glycine as raw material, tap water is solvent, D-3-bromo-camphor sulfonic acid is resolving agent, the method comprises the following steps: 1) racemic para hydroxybenzene glycine being dissolved in Heating temperature is in 75 DEG C of tap water, then resolving agent is added, hybrid reaction 2.5h, obtains the double salt that D-HPG and resolving agent are formed; 2) mass ratio of the double salt that formed of D-HPG and resolving agent and water is 1:2, double salt D-HPG and resolving agent formed is soluble in water, mix with 20% potassium hydroxide solution again, pH value controls about 7, through stirring and crystallizing, be separated, washing drying obtains D-HPG.
The transformation efficiency of the racemic para hydroxybenzene glycine of the present embodiment is in table 1.
Embodiment 5
The method of synthesis D-HPG, take racemic para hydroxybenzene glycine as raw material, tap water is solvent, D-3-bromo-camphor sulfonic acid is resolving agent, the method comprises the following steps: 1) racemic para hydroxybenzene glycine being dissolved in Heating temperature is in 85 DEG C of tap water, then resolving agent is added, hybrid reaction 4h, obtains the double salt that D-HPG and resolving agent are formed; 2) mass ratio of the double salt that formed of D-HPG and resolving agent and water is 1:3, double salt D-HPG and resolving agent formed is soluble in water, mix with the mixing solutions of 20% sodium hydroxide with 20% potassium hydroxide solution again, pH value controls about 7, through stirring and crystallizing, be separated, washing drying obtains D-HPG.
The transformation efficiency of the racemic para hydroxybenzene glycine of the present embodiment is in table 1.
The transformation efficiency of table 1 racemic para hydroxybenzene glycine
| Project | Transformation efficiency |
| Embodiment 1 | 99.85％ |
| Embodiment 2 | 99.95％ |
| Embodiment 3 | 99.95％ |
| Embodiment 4 | 99.98％ |
| Embodiment 5 | 99.91％ |
Learnt by above-mentioned data, racemic para hydroxybenzene glycine can reach 99.9% to D-HPG transformation efficiency, resolving agent unit consumption can reach 0.023 ~ 0.025, D-HPG optically-active can reach-158 ~-160 °, and do not detect dextrorotation D-pHPG, quality product is high, meets international corporation requirement completely.
Claims (7)
1. synthesize the method for D-HPG, it is characterized in that, take racemic para hydroxybenzene glycine as raw material, tap water is solvent, D-3-bromo-camphor sulfonic acid is resolving agent.
2. the method for synthesis D-HPG according to claim 1, it is characterized in that, the method comprises the following steps: 1) dissolve in tap water by racemic para hydroxybenzene glycine heating, then resolving agent is added, hybrid reaction, obtains the double salt that D-HPG and resolving agent are formed; 2) double salt D-HPG and resolving agent formed is soluble in water, then mixes with alkali lye, through stirring and crystallizing, is separated, and washing drying obtains D-HPG.
3. the method for synthesis D-HPG according to claim 2, is characterized in that, the temperature that described racemic para hydroxybenzene glycine dissolves in tap water is 70 ~ 100 DEG C.
4. the method for synthesis D-HPG according to claim 2, is characterized in that, the time of described hybrid reaction is 2 ~ 6h.
5. the method for synthesis D-HPG according to claim 2, is characterized in that, the mass ratio of the double salt that described D-HPG and resolving agent are formed and water is 1:(1 ~ 3).
6. the method for synthesis D-HPG according to claim 2, is characterized in that, described alkali lye is one or more mixing solutionss in ammoniacal liquor, sodium hydroxide solution or potassium hydroxide solution.
7. the method for synthesis D-HPG according to claim 2, is characterized in that, described mix with alkali lye after the pH value of mixing solutions that obtains be 6 ~ 8.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510760169.1A CN105418443A (en) | 2015-11-06 | 2015-11-06 | Method for synthesizing left-handed p-hydroxyphenyl glycine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510760169.1A CN105418443A (en) | 2015-11-06 | 2015-11-06 | Method for synthesizing left-handed p-hydroxyphenyl glycine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105418443A true CN105418443A (en) | 2016-03-23 |
Family
ID=55497051
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510760169.1A Pending CN105418443A (en) | 2015-11-06 | 2015-11-06 | Method for synthesizing left-handed p-hydroxyphenyl glycine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105418443A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110467537A (en) * | 2019-08-08 | 2019-11-19 | 河南新天地药业股份有限公司 | A kind of preparation process of D-HPG |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101045693A (en) * | 2006-03-29 | 2007-10-03 | 宝山钢铁股份有限公司 | Preparation method of para-hydroxybenzol gylcine |
-
2015
- 2015-11-06 CN CN201510760169.1A patent/CN105418443A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101045693A (en) * | 2006-03-29 | 2007-10-03 | 宝山钢铁股份有限公司 | Preparation method of para-hydroxybenzol gylcine |
Non-Patent Citations (1)
| Title |
|---|
| SHIGEKI YAMADA等: "Preparation of D-p-hydroxyphenyl-glycine. Optical Resolution of DL-p-hydroxyphenylglycine with d-3-bromocamphor-8-sulfonic acid", 《AGRIC.BIOL.CHEM.》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110467537A (en) * | 2019-08-08 | 2019-11-19 | 河南新天地药业股份有限公司 | A kind of preparation process of D-HPG |
| CN110467537B (en) * | 2019-08-08 | 2022-10-04 | 河南新天地药业股份有限公司 | Preparation process of L-p-hydroxyphenylglycine |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103232355B (en) | Environmentally-friendly clean production method of iminodiacetic acid | |
| CN104693082A (en) | Method for preparing methionine | |
| TWI685488B (en) | Method for preparing intermediate of Azotomin (Azoxystyrin) | |
| CN104041675A (en) | Simple preparation method for amino acid microelement chelate | |
| CN105461579A (en) | Preparation method of imino-disuccinic acid and salt thereof | |
| CN102093208B (en) | A kind of L(+) tartaric production method | |
| CN102367238A (en) | Method for synthesizing accelerator N,N-dicyclohexyl-2-benzothiazole sulfenamide | |
| CN104844485B (en) | The clean preparation method of methionine | |
| CN102627306B (en) | Novel method for preparing solid aluminum sulfate by using waste | |
| CN105418443A (en) | Method for synthesizing left-handed p-hydroxyphenyl glycine | |
| CN104557580A (en) | Method for preparing iminodiacetic acid | |
| CN104447202B (en) | A kind of production method of potassium method tetramethylolmethane | |
| CN101734690A (en) | Method for preparing potassium nitrate by solvent extraction method | |
| CN102391206A (en) | Method for producing rubber vulcanization accelerator DZ | |
| CN104529801A (en) | Synthetic method for p-hydroxyphenyl glycine | |
| CN104817468A (en) | Glycine preparation method | |
| CN102241600B (en) | Preparation method of 2-amino butyric acid | |
| CN108658820A (en) | Reduce the methionine production method of by-product sodium sulphate | |
| CN102659571B (en) | Continuous preparation method of herbicide intermediate 2, 4-dichlorphenoxyacetic acid | |
| CN105329952A (en) | Refining method of titanium dioxide by-product ferrous sulfate | |
| CN102757367A (en) | Splitting process of racemic ethyl benzene sulfonic acid | |
| CN102702037A (en) | Method for preparing ethylenediamino ethyl sulfonate | |
| CN102382000A (en) | Production method of D- para hydroxybenzene glycine | |
| CN109879786A (en) | A kind of technique of the continuous rapid synthesis methionine of cyanalcohol method | |
| CN106518704A (en) | Preparation method of salicylamide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160323 |
|
| WD01 | Invention patent application deemed withdrawn after publication |