CN105693496B - A kind of stable isotope13The synthetic method of C or D label P-hydroxybenzoic acid - Google Patents
A kind of stable isotope13The synthetic method of C or D label P-hydroxybenzoic acid Download PDFInfo
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- C07C51/093—Preparation of carboxylic acids or their salts, halides or anhydrides by hydrolysis of —CX3 groups, X being halogen
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Abstract
The present invention relates to a kind of stable isotopes13The synthetic method of C or D label P-hydroxybenzoic acid, the following steps are included: (1) stable isotope labeling phenol and co-catalyst are added into reactor, NaOH aqueous solution and major catalyst are sequentially added under stirring, continues to stir, carbon tetrachloride, heating reaction is added；(2) after reaction, it filters, be acidified, extraction, concentration, recrystallizing to get purpose product is arrived.Compared with prior art, operation of the present invention simple process, reaction condition is mild, without high temperature and pressure, suitable for the synthesis of stable isotope labeling reagent, the product para-selectivity finally obtained reaches 100%, without subsequent chiral separation, purification process is easy, and chemical purity is up to 99% or more, and isotope abundance 99atom% is with first-class.
Description
Technical field
The present invention relates to a kind of stable isotope labelled compound fields, more particularly, to a kind of stable isotope13C or D
Mark the synthetic method of P-hydroxybenzoic acid.
Background technique
Stable isotope labeling P-hydroxybenzoic acid (p-hydroxybenzoic acid) is white needle-like crystals, is steady
Determine an important precursor compound in isotope labeling reagent synthesis process, can be used for synthetic preservative, dyestuff, fungicide
Equal detections stable isotope labeling internal standard reagent, is widely used.Stable isotope and its labeled compound are as a kind of uniqueness
Brand-new material, compared with radioactive isotope, have many advantages, such as property it is stable, it is easy to operate, do not need special protection, make
For a kind of commodity with high technology content and high added value, agricultural, food peace it have been widely used in since 1970s
Entirely, the fields such as life science, environment, clinical medicine, pharmacy.
Parabens compound is a kind of important preservative, is commonly called as paraben esters, with volatility is poor, kills
The features such as bacterium ability is strong and stability is high.Since they have low toxicity, efficient characteristic, it is widely used in medicine, food, makeup
The multiple fields such as product, pesticide, can be used directly, and also can be used as fungicide, organic solvent and the intermediate of organic synthesis.To hydroxyl
Benzoates preservative mainly includes P-hydroxybenzoic acid (first, second, third, fourth, isopropyl, isobutyl) ester etc..P-hydroxybenzoic acid
The antifungal mechanism of ester is mainly to inhibit the activity of microbial cell respiratory system and electron transmission enzyme system, destroys microbial cell
Membrane structure plays anti-corrosion effect.Furthermore in order to enhance its antiseptic property, most countries are made using parabens
When for food preservative, different esters are typically mixed into addition in a certain amount and ratio, using its synergy, are come
Reach anti-corrosion purpose.
Being excessively used for preservative can cause potential health risk in foods and cosmetics, and countries in the world are in cosmetics
The preservative used has clearly stipulate that the clause that China " food additives use sanitary standard " (GB2760-2011) includes
The use scope of parabens and its sodium salt and limitation is used in middle specified in more detail food.Foods and cosmetics etc.
The detection technique of paraben preservative in matrix, in order to reduce influence of the complex matrices to testing result, mesh
Preceding first choice stablizes same position using stable isotope labeling p-hydroxybenzoate as the isotope dilution mass spectrometry of internal standard reagent
Element label P-hydroxybenzoic acid is the important as precursors for synthesizing stable isotope labeling p-hydroxybenzoate.
The synthetic product of isotope labelling P-hydroxybenzoic acid mainly includes P-hydroxybenzoic acid-14C, P-hydroxybenzoic acid-
3,5-D2, P-hydroxybenzoic acid-13C, P-hydroxybenzoic acid -2,3,5,6-D4, P-hydroxybenzoic acid-D2(p-OD-PhCOOD) and
P-hydroxybenzoic acid-18O；Domestic literature not yet finds the report of the synthesis technology in relation to isotope labelling P-hydroxybenzoic acid.
Schou etc. with14C flag potassium cyanide is raw material, and P-hydroxybenzoic acid-is prepared14C, the technology use acute
Drugs14C flag potassium cyanide is raw material, and one position of synthetic product label, it is difficult to meet the needs of internal standard reagent；
Hyeongjin Cho etc. is with phenol-D6For raw material, after para-bromination, grignard reaction, Boron tribromide deoxidation methyl
Obtain P-hydroxybenzoic acid -2,3,5,6-D4, the synthesis route is long, and yield is low, and synthesis difficulty is big, it is difficult to meet economy
Requirement；
Donata Catalano etc. and A.Marini etc. are handed over using natural abundance P-hydroxybenzoic acid as raw material by H-D
It changes reaction and P-hydroxybenzoic acid -2,3-D is prepared2, the process conditions are harsh, and only two D atoms of label, it is difficult to meet
The needs of internal standard reagent；
A kind of stable isotope labeling P-hydroxybenzoic acid -1- is referred in patent WO/2004/06977413The preparation of C
Method: with diethyl malonate-13C is raw material, and P-hydroxybenzoic acid -1- is prepared with 4H- pyrans -4- reactive ketone13C, should
Same of the technique isotope atom of label one, it is difficult to meet the needs of internal standard reagent.
The synthesis technology of natural abundance P-hydroxybenzoic acid mainly uses phenol and carbon dioxide in the high pressure feelings of 8.5MPa
It is synthesized under condition, at 200 DEG C, the process condition is harsh, and raw material isotope labelling phenol is easy in high temperature and pressure
H-D occurs with the H in solvent to exchange, the abundance of synthetic product is caused to dilute, which is not suitable for stable isotope labeling to hydroxyl
The synthesis of yl benzoic acid.
Summary of the invention
It is an object of the present invention to overcome the above-mentioned drawbacks of the prior art and provide a kind of stable isotopes13C
Or the synthetic method of D label P-hydroxybenzoic acid.
The purpose of the present invention can be achieved through the following technical solutions:
A kind of stable isotope13The synthetic method of C or D label P-hydroxybenzoic acid, comprising the following steps:
(1) stable isotope labeling phenol and co-catalyst are added into reactor, is sequentially added under stirring
NaOH aqueous solution and major catalyst continue to stir, and carbon tetrachloride, heating reaction is added；
(2) after reaction, it filters, be acidified, extraction, concentration, recrystallizing to get purpose product is arrived.
The stable isotope labeling phenol is phenol-13C6Or phenol-D6, structural formula is respectively as follows:
The major catalyst is β-CD (cyclodextrine)；
The co-catalyst is selected from one or more of copper powder, copper sulphate or copper chloride.
The molar ratio of the additive amount of the major catalyst and stable isotope labeling phenol is 0.1~0.2:1；
The additive amount of the co-catalyst is the 0.1%~1% of mole additive amount of stable isotope labeling phenol.
The concentration of the NaOH aqueous solution is 30~40wt%, and additive amount meets NaOH and stable isotope labeling benzene
The molar ratio of phenol is 6.5~10:1.
The molar ratio of the additive amount of stable isotope labeling phenol and carbon tetrachloride is 1:(2.5~6).
The process conditions of heating reaction in step (1) are as follows: reaction temperature is 85~110 DEG C, and the reaction time is 4~13h.
After NaOH aqueous solution and major catalyst is added, continues 20~40min of stirring, add carbon tetrachloride.
Acidification extracts to be acidified with hydrochloric acid to be extracted with chloroform in step (2).
The present invention with stable isotope labeling phenol, sodium hydrate aqueous solution, carbon tetrachloride etc. by, for raw material, and being added
The catalyst system of β-CD and co-catalyst composition obtain stable isotope labeling so as to react under conditions of more mild
P-hydroxybenzoic acid product.When stable isotope labeling phenol is phenol-13C6When, corresponding purpose product is para hydroxybenzene first
Acid-13C6, synthetic route are as follows:
When stable isotope labeling phenol is phenol-D6When, corresponding purpose product is P-hydroxybenzoic acid-D5When, it closes
At route are as follows:
Synthesis of the invention is identical as the synthesis mechanism of natural abundance P-hydroxybenzoic acid synthesis technology, but due to excessive
Hydroxyl hydrogen on NaOH meeting attack phenyl ring is to cause abundance to dilute, the P-hydroxybenzoic acid synthesis technology of existing natural abundance
In, the additive amount of NaOH is 10 times of the technique or more, is not used to the synthesis of stable isotope labeling P-hydroxybenzoic acid.This
Invention with the synthesis technology of natural abundance P-hydroxybenzoic acid the difference lies in that first is that improving the additive amount of NaOH and being limited
Fixed, can NaOH be to cause the diluted most important factor of abundance, while and determining to react the essential condition that go on smoothly.Naturally
The synthesis process of abundance P-hydroxybenzoic acid is diluted without the concern for abundance, and therefore, the additional amount of NaOH need to only guarantee to react suitable
Benefit carries out and obtains good yield, and in the present invention, if not being defined to NaOH, according to existing natural abundance pair
Hydroxybenzoic acid synthetic technological condition carries out the synthesis of stable isotope isotope labelling P-hydroxybenzoic acid, certainly will will cause same
The dilution of the plain abundance in position, the present invention are defined by the additional amount to NaOH, and synthetic product stable isotope labeling is to hydroxyl
The abundance of benzoic acid is without dilution；Second is that charge ratio, stable isotope labeling phenol of the invention and CCl4Additional amount ratio, no
It is only advantageous that reaction has been pushed to carry out to the right, meanwhile, it may make isotope atom utilization rate under the premise of abundance is not diluted
Reach highest, fully ensures that isotope atom economy.Third is that reaction temperature, reaction temperature is excessively high, sends out active H and D
Raw exchange, so that the abundance of product be caused to dilute, temperature is too low, and reaction is difficult to carry out.
Compared with prior art, the invention has the following advantages that
(1) operation of the present invention simple process, reaction condition is mild, is not necessarily to high temperature and pressure, stable isotope labeling phenol is not
H-D can occur with aqueous solvent to exchange, the isotope abundance of last product obtained is high, suitable for stable isotope labeling reagent
Synthesis.
(2) isotope labelled form based on different products can make product by selecting suitable catalyst system
Para-selectivity reaches 100%, is not necessarily to subsequent chiral separation, and purification process is easy.
(3) chemical purity of products therefrom of the present invention is up to 99% or more, isotope abundance 99atom% or more, and mass number
Difference can satisfy subsequent preservative detection Isotopic Internal Standard stable reagent isotope labelling para hydroxybenzene at 3 or more
The requirement of intermediate needed for formate ester reagent synthesizes has good practical value and economic value.
Specific embodiment
The present invention is described in detail combined with specific embodiments below.
Embodiment 1
Stable isotope labeling P-hydroxybenzoic acid-D5Synthetic method, the specific synthesis process of this method includes following step
It is rapid:
10g (0.1mol) stable isotope labeling phenol-D is added in the reactor6With co-catalyst copper powder, stirring
Under, the NaOH aqueous solution 86.67g that mass concentration is 30wt% is added dropwise, it is finely ground that 11.35g (0.01mol) is added with vigorous stirring
β-CD catalyst；After stirring 30 minutes, 24.1mL (0.25mol) carbon tetrachloride is added, reacts 4h at 85 DEG C；Reaction terminates
Afterwards, it filters, hydrochloric acid acidification, chloroform extraction is concentrated, recrystallization, dries in vacuum oven to constant weight, obtains product stable isotope
Mark P-hydroxybenzoic acid-D5White crystal 10.19g, yield 71.22%, chemical purity 99.09%, para-selectivity are
100%, isotope abundance 99.10atom%D.
Embodiment 2
Stable isotope labeling P-hydroxybenzoic acid-D5Synthetic method, the specific synthesis process of this method includes following step
It is rapid:
10g (0.1mol) stable isotope labeling phenol-D is added in the reactor6With co-catalyst copper sulphate, shape is stirred
Under state, the NaOH aqueous solution 100g that mass concentration is 40wt% is added dropwise, it is finely ground that 22.70g (0.02mol) is added with vigorous stirring
β-CD catalyst；After stirring 30 minutes, 57.9mL (0.6mol) carbon tetrachloride is added, reacts 13h at 110 DEG C；Reaction terminates
Afterwards, it filters, hydrochloric acid acidification, chloroform extraction is concentrated, recrystallization, and vacuum oven is dry to constant weight, obtains product stable isotope mark
Remember P-hydroxybenzoic acid-D5White crystal 11.89g, yield 83.05%, chemical purity 99.01%, para-selectivity are
100%, isotope abundance 99.12atom%D.
Embodiment 3
Stable isotope labeling P-hydroxybenzoic acid-D5Synthetic method, the specific synthesis process of this method includes following step
It is rapid:
10g (0.1mol) stable isotope labeling phenol-D is added in the reactor6With co-catalyst copper chloride, shape is stirred
Under state, the NaOH aqueous solution 80g that mass concentration is 35wt% is added dropwise, it is finely ground that 17.03g (0.015mol) is added with vigorous stirring
β-CD catalyst；After stirring 30 minutes, 38.6mL (0.4mol) carbon tetrachloride is added, reacts 9h at 100 DEG C；Reaction terminates
Afterwards, it filters, hydrochloric acid acidification, chloroform extraction is concentrated, recrystallization, and vacuum oven is dry to constant weight, obtains product stable isotope mark
Remember P-hydroxybenzoic acid-D5White crystal 11.25g, yield 78.61%, chemical purity 99.14%, para-selectivity are
100%, isotope abundance 99.03atom%D.
Embodiment 4
Stable isotope labeling P-hydroxybenzoic acid-13C6Synthetic method, the specific synthesis process of this method includes following step
It is rapid:
10g (0.1mol) stable isotope labeling phenol-is added in the reactor13C6With co-catalyst copper powder, shape is stirred
Under state, the NaOH aqueous solution 86.67g that mass concentration is 30wt% is added dropwise, 11.35g (0.01mol) is added with vigorous stirring and grinds
Thin β-CD catalyst；After stirring 30 minutes, 24.1mL (0.25mol) carbon tetrachloride is added, reacts 4h at 85 DEG C；Reaction knot
Shu Hou is filtered, hydrochloric acid acidification, and chloroform extraction is concentrated, recrystallization, is dried in vacuum oven to constant weight, is obtained product and stablize same position
Element label P-hydroxybenzoic acid-13C6White crystal 10.40g, yield 72.15%, chemical purity 99.10%, para-selectivity
It is 100%, isotope abundance 99.35atom%13C。
Embodiment 5
Stable isotope labeling P-hydroxybenzoic acid-13C6Synthetic method, the specific synthesis process of this method includes following step
It is rapid:
10g (0.1mol) stable isotope labeling phenol-is added in the reactor13C6With co-catalyst copper chloride, stirring
Under state, the NaOH aqueous solution 100g that mass concentration is 40wt% is added dropwise, 22.70g (0.02mol) is added with vigorous stirring and grinds
Thin β-CD catalyst；After stirring 30 minutes, 57.9mL (0.6mol) carbon tetrachloride is added, reacts 13h at 110 DEG C；Reaction knot
Shu Hou is filtered, hydrochloric acid acidification, and chloroform extraction is concentrated, recrystallization, and vacuum oven is dry to constant weight, obtains product stable isotope
Mark P-hydroxybenzoic acid-13C6White crystal 12.34g, yield 85.65%, chemical purity 99.05%, para-selectivity are
100%, isotope abundance 99.26atom%13C。
Embodiment 6
Stable isotope labeling P-hydroxybenzoic acid-13C6Synthetic method, the specific synthesis process of this method includes following step
It is rapid:
10g (0.1mol) stable isotope labeling phenol-is added in the reactor13C6With co-catalyst copper sulphate, stirring
Under state, the NaOH aqueous solution 80g that mass concentration is 35wt% is added dropwise, 17.03g (0.015mol) is added with vigorous stirring and grinds
Thin β-CD catalyst；After stirring 30 minutes, 38.6mL (0.4mol) carbon tetrachloride is added, reacts 9h at 100 DEG C；Reaction knot
Shu Hou is filtered, hydrochloric acid acidification, and chloroform extraction is concentrated, recrystallization, and vacuum oven is dry to constant weight, obtains product stable isotope
Mark P-hydroxybenzoic acid-13C6White crystal 10.89g, yield 75.55%, chemical purity 99.06%, para-selectivity are
100%, isotope abundance 99.25atom%13C。
Embodiment 7
Stable isotope labeling P-hydroxybenzoic acid-13C6Synthetic method, the specific synthesis process of this method includes following step
It is rapid:
0.1mol stable isotope labeling phenol-is added in the reactor13C6With co-catalyst copper sulphate 0.001mol,
Under stirring, the NaOH aqueous solution 100g that mass concentration is 35wt% is added dropwise, it is finely ground that 0.018mol is added with vigorous stirring
β-CD catalyst；Stirring after twenty minutes, is added 0.5mol carbon tetrachloride, reacts 6h at 100 DEG C；After reaction, it filters,
Hydrochloric acid acidification, chloroform extraction, is concentrated, recrystallization, and vacuum oven is dry to constant weight, obtains product stable isotope labeling to hydroxyl
Benzoic acid-13C6White crystal.It is calculated through detection, yield 77.25%, chemical purity 99.36%, para-selectivity is
100%, isotope abundance 99.45atom%13C。
Embodiment 8
Stable isotope labeling P-hydroxybenzoic acid-13C6Synthetic method, the specific synthesis process of this method includes following step
It is rapid:
0.1mol stable isotope labeling phenol-is added in the reactor13C6With co-catalyst copper sulphate 0.0001mol,
Under stirring, the NaOH aqueous solution 100g that mass concentration is 32wt% is added dropwise, it is finely ground that 0.018mol is added with vigorous stirring
β-CD catalyst；Stirring after forty minutes, is added 0.5mol carbon tetrachloride, reacts 11h at 95 DEG C；After reaction, it filters,
Hydrochloric acid acidification, chloroform extraction, is concentrated, recrystallization, and vacuum oven is dry to constant weight, obtains product stable isotope labeling to hydroxyl
Benzoic acid-13C6White crystal.It is calculated through detection, yield 78.33%, chemical purity 99.12%, para-selectivity is
100%, isotope abundance 99.53atom%13C。
Embodiment 9
Stable isotope labeling P-hydroxybenzoic acid-13C6Synthetic method, the specific synthesis process of this method includes following step
It is rapid:
0.1mol stable isotope labeling phenol-is added in the reactor13C6With co-catalyst copper sulphate 0.0005mol,
Under stirring, the NaOH aqueous solution 100g that mass concentration is 32wt% is added dropwise, it is finely ground that 0.018mol is added with vigorous stirring
β-CD catalyst；Stirring after forty minutes, is added 0.5mol carbon tetrachloride, reacts 11h at 95 DEG C；After reaction, it filters,
Hydrochloric acid acidification, chloroform extraction, is concentrated, recrystallization, and vacuum oven is dry to constant weight, obtains product stable isotope labeling to hydroxyl
Benzoic acid-13C6White crystal.It is calculated through detection, yield 78.48%, chemical purity 99.18%, para-selectivity is
100%, isotope abundance 99.58atom%13C。
The above description of the embodiments is intended to facilitate ordinary skill in the art to understand and use the invention.
Person skilled in the art obviously easily can make various modifications to these embodiments, and described herein general
Principle is applied in other embodiments without having to go through creative labor.Therefore, the present invention is not limited to the above embodiments, ability
Field technique personnel announcement according to the present invention, improvement and modification made without departing from the scope of the present invention all should be of the invention
Within protection scope.
Claims (2)
1. a kind of stable isotope13The synthetic method of C or D label P-hydroxybenzoic acid, which comprises the following steps:
(1) stable isotope labeling phenol and co-catalyst are added into reactor, NaOH water is sequentially added under stirring
Solution and major catalyst continue to stir, and carbon tetrachloride, heating reaction is added；
(2) after reaction, it filters, be acidified, extraction, concentration, recrystallizing to get purpose product is arrived；
The major catalyst is β-CD；
The co-catalyst is selected from one or more of copper powder, copper sulphate or copper chloride；
The concentration of the NaOH aqueous solution is 30~40wt%, and additive amount meets NaOH and stable isotope labeling phenol
Molar ratio is 6.5~10:1；
The process conditions of heating reaction in step (1) are as follows: reaction temperature is 85~110 DEG C, and the reaction time is 4~13h；
The molar ratio of the additive amount of the major catalyst and stable isotope labeling phenol is 0.1~0.2:1；
The additive amount of the co-catalyst is the 0.1%~1% of mole additive amount of stable isotope labeling phenol；
The molar ratio of the additive amount of stable isotope labeling phenol and carbon tetrachloride is 1:(2.5~6)；
After NaOH aqueous solution and major catalyst is added in step (1), continues 20~40min of stirring, add carbon tetrachloride；
Acidification extracts to be acidified with hydrochloric acid to be extracted with chloroform in step (2).
2. a kind of stable isotope according to claim 113The synthetic method of C or D label P-hydroxybenzoic acid, feature
It is, the stable isotope labeling phenol is phenol-13C6Or phenol-D6, structural formula is respectively as follows:
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3029276A (en) * | 1958-06-25 | 1962-04-10 | Bayer Ag | Process for the production of 3, 5-disubstituted-4-hydroxy benzoic acids and their esters |
| WO2004069774A2 (en) * | 2003-02-04 | 2004-08-19 | The University Court Of The University Of St Andrews | Synthesis of 13c-labelled estrogen analogues |
| CN102690195A (en) * | 2012-03-06 | 2012-09-26 | 江苏添鑫生物工程有限公司 | Para-hydroxybenzoic acid continuous production technique by liquid-phase method |
-
2016
- 2016-03-18 CN CN201610157322.6A patent/CN105693496B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3029276A (en) * | 1958-06-25 | 1962-04-10 | Bayer Ag | Process for the production of 3, 5-disubstituted-4-hydroxy benzoic acids and their esters |
| WO2004069774A2 (en) * | 2003-02-04 | 2004-08-19 | The University Court Of The University Of St Andrews | Synthesis of 13c-labelled estrogen analogues |
| CN102690195A (en) * | 2012-03-06 | 2012-09-26 | 江苏添鑫生物工程有限公司 | Para-hydroxybenzoic acid continuous production technique by liquid-phase method |
Non-Patent Citations (2)
| Title |
|---|
| 新型聚苯乙烯键联U-环糊精的制备及其催化羧化性能;张胜民 等;《湖北工学院学报》;19961230;第11卷(第4期);56-58 |
| 硅胶负载β-环糊精催化剂用于4-羟基苯甲酸的选择性合成;张胜民 等;《武汉工业大学学报》;19960630;第18卷(第2期);29-30 |
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