CN105527365B - Analyze α fluoromethacrylates and its method about material - Google Patents
Analyze α fluoromethacrylates and its method about material Download PDFInfo
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Abstract
The invention discloses a kind of analysis α fluoromethacrylates and its method about material, chromatographic condition is：Chromatographic column uses polarity capillary chromatographic column；Temperature control mode is temperature programming, and sample introduction shunt mode, carrier gas is nitrogen；Detector is flame ionization ditector；α fluoromethacrylates and reference substance are prepared with the first solvent and the second solvent；Wherein, first solvent is acetone and/or acetonitrile, and second solvent is derivatization reagent；α fluoromethacrylates and reference substance solution are placed in injector, after balance, sample or reference substance is injected into gas chromatograph, α fluoromethacrylates and its measure about material is completed.Impurity present in α fluoromethacrylates and its synthesis can be carried out by separation rapidly and efficiently, effectively control synthetic reaction process and product quality under same chromatographic condition using this method.The detection method is easy to operate, sensitivity is high, accuracy is strong, can comprehensively, effectively control product quality.
Description
Technical field
The invention belongs to Pharmaceutical Analysis technical field, specifically, alpha-fluoro acrylic acid first is analyzed the present invention relates to one kind
Ester and its method about material.
Background technology
In recent years, alpha-fluoro methyl acrylate and the like applies more and more, demand in medicine and materials industry
Amount is also increasing therewith.The polymer particularly made by raw material of acrylate is in information industry using quite varied；
In field of medicaments, by alpha-fluoro methyl acrylate be the polymer for preparing of raw material after being combined with some high medicines of activity,
New drug can be made, enters into the human body as Transfer Medium, the unnecessary potassium of some human bodies, sodium ion etc. is excreted.
Wherein, R, X are separately any one in following each group：C1-C3Alkyl, X is halogen group.
Alpha-fluoro methyl acrylate can use synthetic route as one kind in compound shown in Formulas I：Methylfluoracetate+
Dimethyl oxalate → enol sodium salt or sylvite → alpha-fluoro methyl acrylate, still, the accessory substance that easily remains in the product and miscellaneous
Matter includes：Methanol (MeOH), t-butyl methyl ether (MtBE), dimethyl carbonate (DMC), 2,6- tert-butyl-4-methyl-Phenols
(BHT), methylfluoracetate (MFAc), toluene (Toluene).On the other hand, in view of enol sodium salt/sylvite of alkane reaction generation
Intermediate is out of order, it is not easy to separate, and the production cycle can extend, and causes production cost and cost of labor increase, therefore this
Synthetic route is not very suitable for industrialized production.Although it has been reported that：Can be without separating in the middle of enol sodium salt/sylvite
Body, directly carries out second step reaction, but is due to the by-product carbinol that there will necessarily be in reacting, and can cause enol sodium salt/sylvite
Generation reversible reaction, causes operator to think the unclosed illusion of reaction, influences process, so as to cause second step reaction miscellaneous
Matter increases, and product yield is low and process costs are high.Therefore strict control is carried out to building-up process and shows important especially, is produced with full-scope safeguards
Quality and production safety, and effectively reduce production cost.
At present, analysis alpha-fluoro methyl acrylate and its method about material still have much room for improvement.
The content of the invention
It is contemplated that at least solving one of technical problem in correlation technique to a certain extent.Therefore, the present invention
One purpose is to propose a kind of analysis alpha-fluoro methyl acrylate and its method about material, and this method can be controlled accurately
First step reaction mass, while determining alpha-fluoro methyl acrylate content.By under same chromatographic condition quick separating analyze
Major product and relevant material [including methanol (MeOH), t-butyl methyl ether (MtBE), dimethyl carbonate (DMC), the 2,6- tert-butyl groups-
4- methylphenols (BHT), methylfluoracetate (MFAc), toluene, enol sodium salt or sylvite], realize alpha-fluoro methyl acrylate
Quality control, meets the industrialized production of product.
In one aspect of the invention, the invention provides a kind of alpha-fluoro methyl acrylate and its relevant material analyzed
Method.It is characterized in that：
(1) chromatographic condition：
Chromatographic column uses polarity capillary chromatographic column；
Temperature control mode is temperature programming, and sample introduction shunt mode, carrier gas is nitrogen；
Detector is flame ionization ditector；
(2) preparation of sample solution：By alpha-fluoro methyl acrylate and reference substance separately with the first solvent and
The mixed solvent of two solvents is prepared；
Wherein, first solvent is acetone and/or acetonitrile, and second solvent is derivatization reagent；
(3) determine：Obtained alpha-fluoro methyl acrylate solution will be prepared in step (2) and reference substance solution is placed in sample introduction
In device, after balance, gas chromatograph is injected into, alpha-fluoro methyl acrylate and its measure about material is completed.
Alpha-fluoro methyl acrylate and reference substance are prepared with the first solvent and derivatization reagent, the trifluoro in derivatization reagent
Acetic acid is 3~45% with sample quality percentage.
Analysis alpha-fluoro methyl acrylate according to embodiments of the present invention and its method about material, can be effectively right
Methanol (MeOH) in product, t-butyl methyl ether (MtBE), dimethyl carbonate (DMC), 2,6- tert-butyl-4-methyl-Phenols (BHT),
Methylfluoracetate (MFAc), toluene (Toluene) and enol sodium salt or sylvite are detected that its testing result has significant
Sensitivity, stability and repeatability.By adding derivatization reagent in the sample preparation stage, the not alkene of appearance can be made in detection
Sodium alkoxide or sylvite without separate just can Accurate Determining raw material methylfluoracetate and enol sodium salt or sylvite, it is of the invention
Analysis method accuracy is strong, easy to operate, can effective control for product quality.
, can be with addition, analysis alpha-fluoro methyl acrylate according to embodiments of the present invention and its method about material
With following additional technical feature：
In some embodiments of the invention, temperature programming is carried out to chromatographic column：During 0~10min, column temperature remains 35~
A steady temperature between 45 DEG C, rises to 50~60 DEG C with 2~8 DEG C/min afterwards, then 200 are risen to 20~30 DEG C/min~
250 DEG C, keep 3~7min.It is possible thereby to efficiently separate alpha-fluoro methyl acrylate and relevant material.
In some embodiments of the invention, the split ratio of the shunt mode is 30:1~60:1, preferably 50:1.By
This, can significantly improve detection sensitivity.
In some embodiments of the invention, the derivatization reagent is the mixed solvent of organic acid and organic reagent.
It is possible thereby to fully sample dissolution, and improve peak type.
In some embodiments of the invention, the organic acid is trifluoroacetic acid.It is possible thereby to reduce the damage to instrument
Wound, while further improving alpha-fluoro methyl acrylate and the separating degree about material.
In some embodiments of the invention, the organic reagent is acetone and/or acetonitrile.It is possible thereby to fully dissolve sample
Detection of the product without disturbing impurity.
In some embodiments of the invention, the mass ratio of the organic acid and the trifluoroacetic acid is 1-3g：50-
200mg.It is possible thereby to fully detection of the sample dissolution without disturbing impurity.
In some embodiments of the invention, the percentage of the organic acid and sample quality is 3~45%.Acid addition
Amount can not enough make enol sodium salt or sylvite dissociate not thoroughly, and testing result is inaccurate, and addition is excessive, enol sodium salt or sylvite trip
Impurity peaks, interference measurement occur before amorph peak, and peak type is bad, it is also possible to damage instrument.According to the specific of the present invention
Sample in embodiment, the percentage of above-mentioned organic acid and sample quality refers to alpha-fluoro methyl acrylate or reference substance.
In some embodiments of the invention, the temperature of the detector is 230~260 degrees Celsius, and preferably 250 is Celsius
Degree.Thus, it is possible to further improve the separating degree of each component in alpha-fluoro methyl acrylate.
In some embodiments of the invention, the particle diameter of filler is 0.1-0.5 μm in the chromatographic column.Thus, it is possible to enter
One step improves the separating degree of each component in alpha-fluoro methyl acrylate.
In some embodiments of the invention, the analysis method uses 30m × 0.32mm, 0.25 μm of DB-wax chromatograms
Post, carries out temperature programming, and condition is：
| Heating rate (DEG C/min) | Temperature (DEG C) | Retention time (min) | Run time (min) |
| 40 | 8 | 8 | |
| 5 | 60 | 0 | 12 |
| 25 | 230 | 5 | 23.8 |
Wherein, injector temperature is 230 degrees Celsius, and detector temperature is 250 degrees Celsius, and flow velocity is 1ml/min, sample introduction body
Product is 1 μ L, split ratio 50:1.
Thus, it is possible to be examined while effectively realizing alpha-fluoro methyl acrylate and methylfluoracetate, enol sodium salt or sylvite
Survey.
In some embodiments of the invention, the analysis method uses 30m × 0.32mm, 0.25 μm of DB-wax chromatograms
Post, carries out temperature programming, and condition is：
| Heating rate (DEG C/min) | Temperature (DEG C) | Retention time (min) | Run time (min) |
| 40 | 8 | 8 | |
| 5 | 60 | 0 | 12 |
| 25 | 200 | 6 | 23.6 |
Wherein, injector temperature is 240 degrees Celsius, and detector temperature is 250 degrees Celsius, and flow velocity is 1ml/min, sample introduction body
Product is 1 μ L, split ratio 50:1.
Thus, it is possible to effectively realize alpha-fluoro methyl acrylate (MFA) and methylfluoracetate (MFAc), methanol (MeOH),
T-butyl methyl ether (MtBE), dimethyl carbonate (DMC), 2,6- tert-butyl-4-methyl-Phenols (BHT), toluene (Toluene) it is same
When detect.
In some embodiments of the invention, impurity positioning solution includes methylfluoracetate (MFAc), carbonic acid diformazan respectively
Ester (DMC), t-butyl methyl ether (MtBE), 2,6- tert-butyl-4-methyl-Phenols (BHT), toluene (Toluene), methanol (MeOH),
Wherein, BHT concentration is 0.08mg/mL, and other concentration are 0.4mg/mL.Thus, it is possible to while sample size is reduced as far as possible,
So that response is met the need for determining, it is to avoid continuous high-concentration sample introduction, extend the service life of chromatographic column.And in the concentration
Under, it is kept completely separate between main component alpha-fluoro methyl acrylate and other peaks.
The elution separating effect of the inventive method preferably, can make 6 impurity in sample efficiently separate and quantitatively detect.Detection
Time only needs 24min.Product quantitative limit concentration is 24 μ g/mL, can the sour first of quick, accurate, reliable separating alpha-fluoropropenes
Ester and adjacent impurity.
The additional aspect and advantage of the present invention will be set forth in part in the description, and will partly become from the following description
Obtain substantially, or recognized by the practice of the present invention.
Brief description of the drawings
Fig. 1 shows the gas-chromatography of embodiments in accordance with the present invention 1, gained alpha-fluoro methyl acrylate and impurity positioning
Figure；
Fig. 2 shows the gas chromatogram of embodiments in accordance with the present invention 2, gained alpha-fluoro methyl acrylate and impurity；
Fig. 3 shows embodiments in accordance with the present invention 3, the gas chromatogram of gained alpha-fluoro methyl acrylate reaction solution；
Fig. 4 shows embodiments in accordance with the present invention 4, gained alpha-fluoro methyl acrylate intermediate enol sodium salt and impurity
Gas chromatogram；
Fig. 5 shows embodiments in accordance with the present invention 4, gained alpha-fluoro methyl acrylate intermediate enol sodium salt and impurity
Gas chromatogram；
Fig. 6 shows the comparative example 1 according to the present invention, gained alpha-fluoro methyl acrylate intermediate enol sodium salt and impurity
Gas chromatogram.
Fig. 7 shows the comparative example 2 according to the present invention, gained alpha-fluoro methyl acrylate intermediate enol sodium salt and impurity
Gas chromatogram.
Embodiment
Embodiments of the invention are described below in detail.The embodiments described below is exemplary, is only used for explaining this hair
It is bright, and be not considered as limiting the invention.Unreceipted particular technique or condition in embodiment, according to text in the art
Offer described technology or condition or carried out according to product description.Agents useful for same or the unreceipted production firm person of instrument,
For can be by the conventional products of acquisition purchased in market.
In the embodiment of the present invention alpha-fluoro methyl acrylate used and enol sodium salt or sylvite intermediate be applicant from
System.
Alpha-fluoro methyl acrylate and enol sodium salt through methylfluoracetate+dimethyl oxalate → enol sodium salt or sylvite → α-
Fluoromethacrylate synthesis is obtained.
Embodiment 1
Instrument：Agilent7890A gas chromatographs, fid detector
Chromatographic column：DB-wax(30m×0.32mm×0.25μm)；
Temperature programming condition is：
| Heating rate (DEG C/min) | Temperature (DEG C) | Retention time (min) | Run time (min) |
| 40 | 8 | 8 | |
| 5 | 60 | 0 | 12 |
| 25 | 200 | 6 | 23.6 |
Flow velocity：1.0mL/min
Detector temperature：250℃
Injector temperature：240℃
Sampling volume：1μL
Split ratio：50:1
Diluent：Acetonitrile
Derivatization reagent：60mg trifluoroacetic acids are added in 2g acetonitriles
Run time：23.6min
Experimental procedure：
BHT reference substance stock solutions：BHT reference substances about 80mg, it is accurately weighed, put in 50mL volumetric flasks, plus diluent is molten
Solve and be diluted to scale, shake up.
Sample and each component reference substance solution：Weigh alpha-fluoro methyl acrylate reference substance about 80mg, weigh MeOH,
Toluene, MtBE, DMC, MFAc reference substance each about 40mg, it is accurately weighed, put in 100mL volumetric flasks, then precision pipettes 5mL
BHT reference substance stock solutions, put in above-mentioned 100mL volumetric flasks, plus 1mL derivatization reagents, then are dissolved and be diluted to diluent
Scale, shakes up.
Quantitative limit solution：Precision pipettes 5mL BHT reference substance stock solutions, is placed in 100mL volumetric flasks and dilutes constant volume, then
Precision pipettes 1mL BHT solution, puts in 10mL volumetric flasks, plus diluent is diluted to scale, shakes up (0.008mg/mL), equivalent to
40ppm。
Experimental result：
Alpha-fluoro methyl acrylate and the gas chromatogram of impurity positioning are as shown in figure 1, its data is shown in Table 1.
The alpha-fluoro methyl acrylate of table 1 and impurity positioning result
| Analyte | Retention time | Separating degree |
| T-butyl methyl ether (MtBE) | 3.63min | 78.74 |
| Methanol (MeOH) | 7.56min | 33.57 |
| Dimethyl carbonate (DMC) | 11.28min | 4.06 |
| Alpha-fluoro methyl acrylate (MFA) | 11.84min | - |
| Toluene (Toluene) | 13.06min | 11.23 |
| 2- methylfluoracetates (MFAc) | 14.16min | 23.25 |
| 2,6- tert-butyl-4-methyl-Phenols (BHT) | 21.15min | 85.72 |
Conclusion：Under this chromatographic condition, alpha-fluoro methyl acrylate and 6 impurity can be issued to good in same chromatographic condition
Good separation, sample result also shows BHT impurity when content is 40ppm, and it is that can make qualitative point to carry out gas chromatographic analysis
Analysis, quantitatively it is limited to 40ppm.
Embodiment 2
Instrument：Agilent7890A gas chromatographs, fid detector
Chromatographic column：DB-wax(30m×0.32mm×0.25μm)；
Temperature programming condition is：
| Heating rate (DEG C/min) | Temperature (DEG C) | Retention time (min) | Run time (min) |
| 40 | 8 | 8 | |
| 5 | 60 | 0 | 12 |
| 25 | 200 | 6 | 23.6 |
Flow velocity：1.0mL/min
Detector temperature：250℃
Injector temperature：240℃
Sampling volume：1μL
Split ratio：50:1
Diluent：Acetonitrile
Derivatization reagent：60mg trifluoroacetic acids are added in 2g acetonitriles
Run time：23.6 minutes
Experimental procedure：
Impurity content reference substance solution：MFA reference substances about 800mg is taken, it is accurately weighed, put plus good 5mL diluents and 1mL
In the l0mL volumetric flasks of derivatization reagent, plus diluent dissolves and is diluted to scale, shakes up (80mg/mL).Precision pipettes 1mL and put
In 200mL volumetric flasks, plus diluent is diluted to scale, shakes up (0.4mg/mL).
Sample solution：Take MFA samples about 800mg, it is accurately weighed, put plus good 5mL diluents and 1mL derivatization reagents
In 10mL volumetric flasks, plus diluent dissolves and is diluted to scale, shakes up (80mg/mL).
Quantitative limit solution：Precision pipettes 3mL impurity content reference substance solutions, puts in 50mL volumetric flasks, plus dilution dilution agent
To scale, (24 μ g/mL), the content equivalent to 0.03% are shaken up.
Experimental result：
The gas chromatogram of alpha-fluoro methyl acrylate and impurity is as shown in Fig. 2 its data is shown in Table 2.
The alpha-fluoro methyl acrylate of table 2 and defects inspecting result
| Analyte | Retention time | RRF | Content |
| T-butyl methyl ether (MtBE) | 3.63min | 0.53 | 0.02% |
| Methanol (MeOH) | 7.56min | 1.10 | 0.24% |
| Dimethyl carbonate (DMC) | 11.28min | 1.98 | 0.10% |
| Alpha-fluoro methyl acrylate (MFA) | 11.84min | 1.00 | 98.30% |
| Toluene (Toluene) | 13.06min | 0.35 | 0.06% |
| 2- methylfluoracetates (MFAc) | 14.16min | 1.45 | 0.38% |
| 2,6- tert-butyl-4-methyl-Phenols (BHT) | 21.15min | 0.35 | 280ppm |
Conclusion：Under this chromatographic condition, alpha-fluoro methyl acrylate and 6 impurity can be issued to good in same chromatographic condition
Good separation.When principal component alpha-fluoro methyl acrylate concentration is 24 μ g/mL, it is that can make qualitative point to carry out gas chromatographic analysis
Analyse, be quantitatively limited to 0.03% content.As a result show that this method can be used for the quality testing of alpha-fluoro methyl acrylate.
Embodiment 3
Instrument：Agilent7890A gas chromatographs, fid detector
Chromatographic column：DB-wax(30m×0.32mm×0.25μm)；
Temperature programming condition is：
| Heating rate (DEG C/min) | Temperature (DEG C) | Retention time (min) | Run time (min) |
| 40 | 8 | 8 | |
| 5 | 60 | 0 | 12 |
| 25 | 230 | 5 | 23.8 |
Flow velocity：1.0mL/min
Detector temperature：250℃
Injector temperature：230℃
Sampling volume：1μL
Split ratio：50:1
Diluent：Acetone
Derivatization reagent：100mg trifluoroacetic acids are added in 2g acetone
Run time：23.8min
Experimental procedure：Precision weighs MFA reaction solutions about 200mg, adds 1mL derivatization reagents and 1mL diluents, shakes up,
Filtering, is produced.
Conclusion：Under this chromatographic condition, the gas chromatogram of gained alpha-fluoro methyl acrylate reaction solution as shown in figure 3, its
Middle methylfluoracetate appearance 11.304min, enol sodium salt free state appearance 18.775min, MFA appearance 7.449min.Chromatogram
Show that methylfluoracetate and enol sodium salt free state can be issued to well with main composition MFA in same chromatographic condition in reaction solution
Separation.As a result reaction monitoring and quality testing that this method can be used for MFA are shown.
Embodiment 4
Instrument：Agilent7890A gas chromatographs, fid detector
Chromatographic column：DB-wax(30m×0.32mm×0.25μm)；
Temperature programming condition is：
| Heating rate (DEG C/min) | Temperature (DEG C) | Retention time (min) | Run time (min) |
| 40 | 8 | 8 | |
| 5 | 60 | 0 | 12 |
| 25 | 230 | 5 | 23.8 |
Flow velocity：1.0mL/min
Detector temperature：250℃
Injector temperature：230℃
Sampling volume：1μL
Split ratio：50:1
Diluent：Acetone
Derivatization reagent：180mg trifluoroacetic acids are added in 2g acetone
Run time：23.8min
Experimental procedure：Precision weighs enol sodium salt reaction solution about 200mg, adds 1mL derivatization reagents and 0.5mL dilutions
Agent, shakes up, filtering, produces.
Conclusion：Under this chromatographic condition, the gas-chromatography of gained alpha-fluoro methyl acrylate intermediate enol sodium salt and impurity
Figure is as shown in Figure 4 and Figure 5.Wherein methylfluoracetate appearance 11.363min, enol sodium salt free state appearance 18.742min.
Chromatogram 4 shows that enol sodium salt free state can be swum with appearance, methylfluoracetate with enol sodium salt in reaction solution
Amorph is issued to good separation in same chromatographic condition.As a result show that this method can be used for the reaction monitoring and matter of enol sodium salt
Amount detection.Chromatogram 5 is shown a trifluoroacetic acid and adds excessive sample drawing, shows that trifluoroacetic acid needs to control addition,
Miscellaneous peak, influence detection occur before excessive main peak.
Comparative example 1
Instrument：Agilent7890A gas chromatographs, fid detector
Chromatographic column：DB-wax(30m×0.32mm×0.25μm)；
Temperature programming condition is：
| Heating rate (DEG C/min) | Temperature (DEG C) | Retention time (min) | Run time (min) |
| 40 | 8 | 8 | |
| 5 | 60 | 0 | 12 |
| 25 | 230 | 5 | 23.8 |
Flow velocity：1.0mL/min
Detector temperature：250℃
Injector temperature：230℃
Sampling volume：1μL
Split ratio：50:1
Diluent：Acetone
Derivatization reagent：200mg oxalic acid is added in 2g acetone
Run time：23.8min
Experimental procedure：Precision weighs enol sodium salt reaction solution about 180mg, adds 1mL derivatization reagents and 0.5mL dilutions
Agent, shakes up, filtering, produces.
Conclusion：External standard free state product 12.5% is surveyed with the free enol sodium salt of oxalic acid, methylfluoracetate has 28%, it may be possible to
Oxalic acid is acid not enough, dissociates incomplete, method is inaccurate, poor repeatability.
Comparative example 2
Instrument：Agilent7890A gas chromatographs, fid detector
Chromatographic column：DB-wax(30m×0.32mm×0.25μm)；
Temperature programming condition is：
| Heating rate (DEG C/min) | Temperature (DEG C) | Retention time (min) | Run time (min) |
| 40 | 8 | 8 | |
| 5 | 60 | 0 | 12 |
| 25 | 230 | 5 | 23.8 |
Flow velocity：1.0mL/min
Detector temperature：250℃
Injector temperature：230℃
Sampling volume：1μL
Split ratio：50:1
Diluent：Acetone
Derivatization reagent：150mg hydrochloric acid is added in 2g acetone
Run time：23.8min
Experimental procedure：Precision weighs enol sodium salt reaction solution about 180mg, adds 1mL derivatization reagents and 0.5mL dilutions
Agent, shakes up, filtering, produces.
Conclusion：The enol sodium salt that dissociated with oxalic acid surveys external standard free state product and there is no that methylfluoracetate has 7.16%,
19.16min and 21.25min two are had more than larger impurity peaks, it may be possible to which hydrochloric acid is acid too strong, caused newly miscellaneous occur
Matter, method is inaccurate, and acid too strong reagent can also have certain infringement to instrument.
In the description of the invention, it is to be understood that term " first ", " second " are only used for describing purpose, and can not
It is interpreted as indicating or implies relative importance or the implicit quantity for indicating indicated technical characteristic.Thus, define " the
One ", one or more this feature can be expressed or be implicitly included to the feature of " second ".In the description of the invention,
" multiple " are meant that two or more, unless otherwise specifically defined.
In the description of this specification, reference term " one embodiment ", " some embodiments ", " example ", " specifically show
The description of example " or " some examples " etc. means to combine specific features, structure, material or the spy that the embodiment or example are described
Point is contained at least one embodiment of the present invention or example.In this manual, to the schematic representation of above-mentioned term not
Identical embodiment or example must be directed to.Moreover, specific features, structure, material or the feature of description can be with office
Combined in an appropriate manner in one or more embodiments or example.In addition, in the case of not conflicting, the skill of this area
Art personnel can be tied the not be the same as Example or the feature of example and non-be the same as Example or example described in this specification
Close and combine.
Although embodiments of the invention have been shown and described above, it is to be understood that above-described embodiment is example
Property, it is impossible to limitation of the present invention is interpreted as, one of ordinary skill in the art within the scope of the invention can be to above-mentioned
Embodiment is changed, changed, replacing and modification.
Claims (9)
1. a kind of analysis alpha-fluoro methyl acrylate and its method about material, it is characterised in that methods described includes as follows
Step：
(1) chromatographic condition：
Chromatographic column uses polarity capillary chromatographic column；
Temperature control mode is temperature programming, and sample introduction shunt mode, carrier gas is nitrogen；
Detector is flame ionization ditector；
(2) preparation of sample solution：Alpha-fluoro methyl acrylate and reference substance is separately molten with the first solvent and second
The mixed solvent of agent is prepared；
Wherein, first solvent is acetone and/or acetonitrile, and second solvent is derivatization reagent；
(3) determine：Obtained alpha-fluoro methyl acrylate solution will be prepared in step (2) and reference substance solution is placed in injector
In, after balance, gas chromatograph is injected into, alpha-fluoro methyl acrylate and its measure about material is completed,
Temperature programming is carried out to chromatographic column：During 0~10min, column temperature remains a steady temperature between 35~45 DEG C, afterwards
50~60 DEG C are risen to 2~8 DEG C/min, then 200~250 DEG C are risen to 20~30 DEG C/min, 3~7min is kept,
The reference substance is selected from methylfluoracetate, dimethyl carbonate, t-butyl methyl ether, 2,6- tert-butyl-4-methyl-Phenols, first
At least one of benzene and methanol,
The derivatization reagent is the mixed solvent of organic acid and organic reagent, and the organic reagent is acetone and/or acetonitrile,
The organic acid is trifluoroacetic acid.
2. according to the method described in claim 1, it is characterised in that sample introduction split ratio is 30:1~60:1.
3. method according to claim 2, it is characterised in that sample introduction split ratio is 50:1.
4. according to the method described in claim 1, it is characterised in that the mass ratio of the organic reagent and the trifluoroacetic acid is
1-3g：50-200mg.
5. method according to claim 4, it is characterised in that trifluoroacetic acid and sample quality in the derivatization reagent
Percentage is 3~45%.
6. according to the method described in claim 1, it is characterised in that the temperature of the detector is 230~260 degrees Celsius.
7. method according to claim 5, it is characterised in that the temperature of the detector is 250 degrees Celsius.
8. according to the method described in claim 1, it is characterised in that the analysis uses 30m × 0.32mm, 0.25 μm of DB-
Wax chromatographic columns, carry out temperature programming, and condition is：
Wherein, injector temperature is 230 degrees Celsius, and detector temperature is 250 degrees Celsius, and flow velocity is 1mL/min, and sampling volume is
1 μ L, split ratio 50:1.
9. according to the method described in claim 1, it is characterised in that the analysis uses 30m × 0.32mm, 0.25 μm of DB-
Wax chromatographic columns, carry out temperature programming, and condition is：
Wherein, injector temperature is 240 degrees Celsius, and detector temperature is 250 degrees Celsius, and flow velocity is 1mL/min, and sampling volume is
1 μ L, split ratio 50:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510855116.8A CN105527365B (en) | 2015-11-30 | 2015-11-30 | Analyze α fluoromethacrylates and its method about material |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510855116.8A CN105527365B (en) | 2015-11-30 | 2015-11-30 | Analyze α fluoromethacrylates and its method about material |
Publications (2)
| Publication Number | Publication Date |
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| CN105527365A CN105527365A (en) | 2016-04-27 |
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Effective date of registration: 20190604 Address after: 431700 Tianmen Economic Development Zone, Hubei Province Patentee after: HUBEI WATERSTONE BIO-PHARMACEUTICAL TECHNOLOGY CO., LTD. Address before: 430075 Guanggu Biological City B3-4, 666 High-tech Avenue, Donghu New Technology Development Zone, Wuhan City, Hubei Province Patentee before: Waterstone Pharmaceuticals (Wuhan) Co., Ltd. |