CN115340444A - Impurity removal method for organic impurities in absolute ethyl alcohol - Google Patents
Impurity removal method for organic impurities in absolute ethyl alcohol Download PDFInfo
- Publication number
- CN115340444A CN115340444A CN202210840201.7A CN202210840201A CN115340444A CN 115340444 A CN115340444 A CN 115340444A CN 202210840201 A CN202210840201 A CN 202210840201A CN 115340444 A CN115340444 A CN 115340444A
- Authority
- CN
- China
- Prior art keywords
- ethyl alcohol
- absolute ethyl
- stage
- organic impurities
- heating
- 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.)
- Granted
Links
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title claims abstract description 188
- 239000012535 impurity Substances 0.000 title claims abstract description 81
- 238000000034 method Methods 0.000 title claims abstract description 34
- 238000010438 heat treatment Methods 0.000 claims abstract description 27
- 238000001914 filtration Methods 0.000 claims abstract description 25
- 238000003756 stirring Methods 0.000 claims abstract description 21
- 239000004343 Calcium peroxide Substances 0.000 claims abstract description 15
- LHJQIRIGXXHNLA-UHFFFAOYSA-N calcium peroxide Chemical compound [Ca+2].[O-][O-] LHJQIRIGXXHNLA-UHFFFAOYSA-N 0.000 claims abstract description 15
- 235000019402 calcium peroxide Nutrition 0.000 claims abstract description 15
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims abstract description 14
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims abstract description 14
- 238000010992 reflux Methods 0.000 claims abstract description 12
- 239000007787 solid Substances 0.000 claims abstract description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 45
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 39
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 39
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 12
- 239000000920 calcium hydroxide Substances 0.000 claims description 12
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 12
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 claims description 5
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 2
- 235000019441 ethanol Nutrition 0.000 abstract description 23
- 239000003814 drug Substances 0.000 abstract description 10
- 239000000126 substance Substances 0.000 abstract description 10
- 229940079593 drug Drugs 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 5
- 238000006243 chemical reaction Methods 0.000 abstract description 4
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 20
- 229940022682 acetone Drugs 0.000 description 16
- 239000002585 base Substances 0.000 description 14
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 11
- 239000000243 solution Substances 0.000 description 10
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 9
- 239000002253 acid Substances 0.000 description 8
- 238000004817 gas chromatography Methods 0.000 description 8
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 5
- 230000004807 localization Effects 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- -1 acetaldehyde, acetal Chemical class 0.000 description 3
- 229940045942 acetone sodium bisulfite Drugs 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- YNJORDSKPXMABC-UHFFFAOYSA-N sodium;2-hydroxypropane-2-sulfonic acid Chemical compound [Na+].CC(C)(O)S(O)(=O)=O YNJORDSKPXMABC-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000012286 potassium permanganate Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
- C07C29/88—Separation; Purification; Use of additives, e.g. for stabilisation by treatment giving rise to a chemical modification of at least one compound
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the field of medicines, and particularly discloses an impurity removal method for organic impurities in absolute ethyl alcohol, which comprises the steps of adding calcium peroxide into absolute ethyl alcohol, heating, refluxing and filtering to obtain absolute ethyl alcohol in a first stage; adding strong base into the absolute ethyl alcohol in the first stage, reacting at room temperature, and filtering to obtain absolute ethyl alcohol in the second stage; adding weak base into the anhydrous ethanol of the second stage, heating, stirring, reacting, and filtering to obtain anhydrous ethanol of the third stage; and adding sodium bisulfite solid into the absolute ethyl alcohol in the third stage, heating, stirring, reacting, and filtering to obtain the absolute ethyl alcohol with organic impurities removed. The impurity removal method provided by the invention is simple, various chemical reactions are adopted to effectively remove organic impurities in the ethanol, the various chemical methods are carried out step by step according to a specific sequence, a better impurity removal effect can be achieved, the purity i of the prepared anhydrous ethanol is higher, and the method can be widely applied to impurity removal of the medical anhydrous ethanol.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to an impurity removal method for organic impurities in absolute ethyl alcohol.
Background
The absolute ethyl alcohol solution is colorless clear liquid, can easily absorb moisture from the air, can be mixed and dissolved with various organic solvents such as water, chloroform, ether and the like in any ratio, has wider application range, particularly in the medical industry, not only can play the roles of sterilization and disinfection, but also can play the role of treating diseases, the purity of the solution needs to be ensured in the application process of the high-purity absolute ethyl alcohol solution so as to be effectively applied, when the absolute ethyl alcohol solution is applied to the treatment of patients as a medicine, the absolute ethyl alcohol solution firstly forms the inhibition effect of the central nervous system of a human body to cause the states of excitation and subsequent inhibition of the human body, and the existence of some impurities can also cause the toxic symptoms of the patients. Therefore, it is important to remove impurities from medical anhydrous ethanol.
The conventional method for removing impurities from absolute ethyl alcohol generally adopts potassium permanganate to remove impurities by oxidation and then distills the impurities to remove partial impurities except the conventional rectification physical impurities by a rectification tower, but the two methods can only remove partial impurities from the ethyl alcohol, and the rectification method has good impurity removal effect on impurities in the ethyl alcohol, which have a large difference with the boiling point of the ethyl alcohol, but has no obvious impurity removal effect on impurities close to the boiling point of the ethyl alcohol; the potassium permanganate oxidation method can remove unsaturated impurities in the ethanol, and has poor removal capability on saturated structure organic impurities and the like in the ethanol. The domestic and foreign pharmacopoeia has definite regulations on impurities of medicinal absolute ethyl alcohol, wherein the limit of the Chinese pharmacopoeia on methanol in the absolute ethyl alcohol is 0.02%, and the total amount of acetaldehyde and acetal is not more than 0.001%; the limits of acetone and isopropanol in pharmaceutical anhydrous ethanol are specified in the united states pharmacopeia and are required to be no more than 0.008% based on acetone. In combination with the requirements of domestic and foreign pharmacopoeias, we have studied the purification of anhydrous ethanol.
Disclosure of Invention
Aiming at the problems, the invention discloses an impurity removal method for organic impurities in absolute ethyl alcohol, which comprises the following steps:
adding calcium peroxide into absolute ethyl alcohol, heating, refluxing and filtering to obtain absolute ethyl alcohol in the first stage;
adding strong base into the absolute ethyl alcohol in the first stage, reacting at room temperature, and filtering to obtain absolute ethyl alcohol in the second stage;
adding weak base into the absolute ethyl alcohol in the second stage, heating, stirring, reacting, and filtering to obtain absolute ethyl alcohol in the third stage;
and adding sodium bisulfite solid into the absolute ethyl alcohol in the third stage, heating, stirring, reacting, and filtering to obtain the absolute ethyl alcohol with organic impurities removed.
Further, the heating reflux condition is heating to 70-80 ℃ for reflux for 1-4 h.
Furthermore, the addition amount of the calcium peroxide is 3-10 per mill of the mass of the absolute ethyl alcohol.
Further, the reaction time at room temperature is 3-5h.
Further, the strong base comprises one of potassium hydroxide or sodium hydroxide, and the addition amount of the strong base is 3-10 per mill of the mass of the absolute ethyl alcohol.
Further, the heating and stirring conditions in the second stage are heating to 40-50 ℃ and stirring for 2-8 h.
Further, the weak base comprises one of calcium hydroxide or aluminum hydroxide; the addition amount of the weak base is 0.5-5% of the mass of the absolute ethyl alcohol.
Further, the heating and stirring conditions in the third stage are 10-40 ℃ and 4-12 h.
Further, the adding amount of the sodium bisulfite is 1 to 5 percent of the mass of the absolute ethyl alcohol.
Further, the organic impurities in the anhydrous ethanol include acetaldehyde, methanol, acetone, and isopropanol.
The invention has the beneficial effects that:
the invention adopts a chemical method to remove organic impurities in absolute ethyl alcohol, firstly, oxidizing agents such as calcium peroxide and the like are adopted to convert impurities such as methanol and the like in absolute ethyl alcohol into other aldehyde impurities or acid impurities such as formaldehyde and the like under the condition of reflux reaction at 70-80 ℃, and alcohol impurities such as methanol and the like in ethanol are removed; then, the aldehyde substances are converted into acid impurities by utilizing the characteristic of the reaction between strong alkali such as sodium hydroxide, potassium hydroxide and the like and the aldehyde substances, and acetaldehyde and acetal in the acid impurities are removed; then, by utilizing the characteristics of acid substances, adding weak base such as calcium hydroxide and the like into the acid substances, and stirring for 2-8 h at the temperature of 40-50 ℃ by utilizing the characteristics of acid-base neutralization, so as to remove inherent acid impurities in the absolute ethyl alcohol and acid impurities generated in the previous two steps; and finally, adding excessive sodium bisulfite into the mixture to remove acetone in the ethanol to finally obtain the anhydrous ethanol for medicine, wherein the anhydrous ethanol is used for removing organic impurities. The impurity removal method provided by the invention is simple, various chemical reactions are adopted to remove organic impurities in the ethanol, the various chemical methods are carried out step by step according to a specific sequence, a better impurity removal effect is achieved, the purity of the prepared absolute ethanol is higher, and the absolute ethanol can be widely applied to the field of medicines.
Additional features and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objectives and other advantages of the invention will be realized and attained by the structure particularly pointed out in the written description and claims hereof as well as the appended drawings.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and those skilled in the art can also obtain other drawings according to the drawings without creative efforts.
FIG. 1 shows a gas chromatogram of raw anhydrous ethanol in an example of the present invention;
FIGS. 2-6 show gas chromatograms of single-labeled impurities in an embodiment of the invention; wherein fig. 2 is a gas chromatogram of acetaldehyde, fig. 3 is a gas chromatogram of methanol, fig. 4 is a gas chromatogram of acetone, fig. 5 is a gas chromatogram of isopropyl alcohol, and fig. 6 is a gas chromatogram of acetal;
FIG. 7 shows a gas chromatogram of anhydrous ethanol at a first stage in an example of the present invention;
FIG. 8 shows a gas chromatogram of anhydrous ethanol at the second stage in an example of the present invention;
FIG. 9 shows a gas chromatogram of anhydrous ethanol of the third stage in an example of the present invention;
FIG. 10 shows a gas chromatogram of anhydrous ethanol at the fourth stage in the example of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Compared with industrial grade absolute ethyl alcohol and analytical grade absolute ethyl alcohol, the medical absolute ethyl alcohol has stricter requirements on impurities, and each organic impurity in the absolute ethyl alcohol needs to be strictly controlled. The organic impurities in the absolute ethanol include aldehydes, acids, alcohols and acetone, for example, the organic impurities disclosed in the absolute ethanol recorded in '2020 edition of Chinese pharmacopoeia' include methanol, acetaldehyde, acetal, benzene and cyclohexane, and the limit of the organic impurities to the methanol in the absolute ethanol is required to be 0.02%, and the total amount of the acetaldehyde and the acetal is not more than 0.001%, and above this content, the drug is affected.
The invention takes national Shanghai test anhydrous ethanol analytical purification (10009218, production batch number: 20190517) as an example to remove organic impurities in the anhydrous ethanol.
Firstly, carrying out gas chromatography detection on absolute ethyl alcohol, wherein the detection conditions of the gas chromatography are as follows:
and (3) chromatographic column: agilent DB-624 elastic quartz capillary column, 30m × 0.32mm × 1.80 μm; a detector: FID detector, temperature 280 ℃;
the temperature of the vaporization chamber is 200 ℃;
temperature of the column oven: maintaining at 40 deg.c for 6min, raising the temperature to 150 deg.c at 10 deg.c/min and maintaining for 5 min;
the sample injection amount is 0.1 mu L (directly injecting samples as the sample);
the split ratio is 100:1.
the gas chromatogram of the absolute ethyl alcohol obtained under the above detection conditions is shown in FIG. 1, five characteristic peaks are present within 0-16min, and the peak emergence times of the peaks numbered 1, 2, 3, 4 and 5,1 from left to right are 3.694min, the peak emergence time of the peak 2 is 3.892min, the peak emergence time of the peak 3 is 5.306min, the peak emergence time of the peak 4 is 6.123min, and the peak emergence time of the peak 5 is 6.437min.
The single-standard impurity localization is performed according to the above chromatographic conditions, chromatograms obtained by sequentially and independently injecting acetaldehyde, methanol, acetone, isopropanol, and acetal are respectively shown in fig. 2-6, and the acetaldehyde, methanol, acetone, isopropanol, and acetal used in this example are analytical grade. By comparing the peak appearance sequence of the single standard gas chromatogram, the peak 1 is acetaldehyde (3.694 min), the peak 2 is methanol (3.892 min), the peak 3 is ethanol (5.308 min), the peak 4 is acetone (6.133 min), and the peak 5 is isopropanol (6.437 min), as shown in Table 1.
TABLE 1 Absolute ethanol gas chromatography and single-standard results
| Serial number | Time to peak (min) | Area of | Area ratio (%) | Time to peak (min) of standard sample |
| 1 | 3.694 | 12.2318 | 0.13 | Acetaldehyde: 3.695 |
| 2 | 3.892 | 11.0280 | 0.12 | Methanol: 3.890 |
| 3 | 5.308 | 9412.9467 | 99.37 | |
| 4 | 6.133 | 16.6191 | 0.18 | Acetone: 6.133 |
| 5 | 6.437 | 20.1370 | 0.21 | Isopropyl alcohol: 6.436 |
The removing method specifically comprises the following steps:
the method comprises the following steps: adding absolute ethyl alcohol into a 5L three-necked bottle, heating 3-10 per mill calcium peroxide in the bottle according to the mass ratio to 70-80 ℃, refluxing for 1-4 h, filtering, and removing the residual calcium peroxide to obtain the absolute ethyl alcohol in the first stage.
Step two: adding the absolute ethyl alcohol of the first stage into a 5L three-necked bottle, adding strong base such as potassium hydroxide with the mass of 3-10 per mill of the initial absolute ethyl alcohol, reacting for 3-5h at room temperature, filtering, and removing the residual potassium hydroxide to obtain the absolute ethyl alcohol of the second stage. Wherein the strong base comprises one of potassium hydroxide or sodium hydroxide.
Step three: adding the absolute ethyl alcohol in the second stage into a 5L three-necked bottle, adding weak base accounting for 0.5-5% of the initial absolute ethyl alcohol by mass, heating to 40-50 ℃, stirring for 2-8 h, filtering, and removing the residual calcium hydroxide to obtain the absolute ethyl alcohol in the third stage. Wherein the weak base comprises one of calcium hydroxide or aluminum hydroxide.
It should be noted that the references to strong and weak bases in this invention are relative only and are not to be taken as a meaning of the particular strong and weak bases understood in the art.
Step four: and adding the absolute ethyl alcohol in the third stage into a 2L three-necked bottle, adding sodium bisulfite solid accounting for 1-5% of the weight of the initial absolute ethyl alcohol into the three-necked bottle, stirring the mixture for 4-12 h at the temperature of below 40 ℃, filtering the mixture, and removing the residual sodium bisulfite and acetone-acetone sodium bisulfite precipitate to obtain the absolute ethyl alcohol which can be used for medicines and is used for removing organic impurities.
The above method is described in detail with reference to examples. Reagents, raw materials and vessels used in examples of the present invention are commercially available products unless otherwise specified.
Example 1
The method comprises the following steps: adding 1L of absolute ethyl alcohol into a 5L three-necked bottle, adding 5g of calcium peroxide, heating to 70 ℃, refluxing for 1h, and removing the residual calcium peroxide to obtain absolute ethyl alcohol in the first stage;
the gas chromatogram of the absolute ethanol in the first stage is shown in fig. 7, and the results of positioning by combining the gas chromatogram with impurities are shown in table 2:
TABLE 2 gas chromatography results of anhydrous ethanol of the first stage
By combining table 2 and fig. 7 and comparing the original absolute ethyl alcohol gas chromatogram, it can be seen that the impurity peaks at the original methanol (3.892 min) and isopropanol (6.437 min) positions disappear, an unknown impurity peak (10.763 min) is newly added, and the unknown impurity peak is determined to be acetal after single-standard impurity positioning. The area ratio of acetal was 0.23%. The method for treating the ethanol by the calcium peroxide can effectively remove other alcohol impurities in the ethanol.
Step two: adding 0.5g of potassium hydroxide into the absolute ethyl alcohol in the first stage, reacting for 3 hours at room temperature, and filtering to remove the residual potassium hydroxide to obtain the absolute ethyl alcohol in the second stage;
the gas chromatogram of the absolute ethanol in the second stage is shown in fig. 8, and the results of the localization by combining the gas chromatogram with impurities are shown in table 3:
TABLE 3 gas chromatography results for anhydrous ethanol in the second stage
| Serial number | Time to peak (min) | Area of | Area ratio (%) | Name of substance |
| 1 | 3.696 | 11.9752 | 0.13 | |
| 2 | 5.306 | 9281.3805 | 99.70 | |
| 3 | 6.134 | 16.1986 | 0.17 | Acetone (II) |
As can be seen by combining FIG. 8 and Table 3, the order of the peak location by impurities is 1 for acetaldehyde (3.696 min), 2 for ethanol (5.306 min), and 3 for acetone (6.134 min); it is further deduced that the aldehyde impurities in the absolute ethyl alcohol can be removed by using strong alkali such as potassium hydroxide.
Step three: adding 1g of calcium hydroxide into the anhydrous ethanol in the second stage, heating to 40 ℃, stirring for 2 hours, and filtering to remove the residual calcium hydroxide to obtain the anhydrous ethanol in the third stage;
the gas chromatogram of the anhydrous ethanol at the third stage is shown in fig. 9, and the results of localization by combining the gas chromatogram with impurities are shown in table 4:
TABLE 4 gas chromatography results of anhydrous ethanol at the third stage
| Serial number | Time to peak (min) | Area of | Area ratio (%) | Name of substance |
| 1 | 5.304 | 9085.6619 | 99.82 | |
| 2 | 6.133 | 16.0438 | 0.18 | Acetone (II) |
As can be seen from FIG. 9 and Table 4, the order of the peaks located by the impurities is 1 ethanol (5.304 min) and 2 acetone (6.133 min), which proves that the acetaldehyde in ethanol can be removed by calcium hydroxide.
Adding 10g sodium bisulfite solid into the anhydrous ethanol of the third stage, stirring at 40 deg.C for 4h, filtering, and removing residual sodium bisulfite and acetone sodium bisulfite precipitate to obtain anhydrous ethanol for medicine with organic impurities removed (fourth stage).
The gas chromatogram of the absolute ethanol in the fourth stage is shown in fig. 10, and the results of localization by the gas chromatogram in combination with impurities are shown in table 5:
TABLE 5 gas chromatography results of anhydrous ethanol at the third stage
| Serial number | Time to peak (min) | Area of | Area ratio (%) | Name of substance |
| 1 | 5.304 | 8959.4857 | 100.00％ | Ethanol |
As can be seen from FIG. 10 and Table 5, after the fourth stage of removal, the impurities in the commercial absolute ethanol were removed.
Example 2
Adding 1L of anhydrous ethanol into a 5L three-necked bottle, adding 7.5g of calcium peroxide, heating to 75 ℃, refluxing for 4h, and removing residual calcium peroxide to obtain anhydrous ethanol of a first stage;
adding 0.8g of potassium hydroxide into the absolute ethyl alcohol in the first stage, reacting for 5 hours at room temperature, and filtering to remove the residual potassium hydroxide to obtain the absolute ethyl alcohol in the second stage;
adding 2g of calcium hydroxide into the anhydrous ethanol in the second stage, heating to 45 ℃, stirring for 2h, and filtering to remove the residual calcium hydroxide to obtain the anhydrous ethanol in the third stage;
adding 15g of sodium bisulfite solid into the anhydrous ethanol in the third stage, stirring for 8h at the temperature below 40 ℃, filtering, and removing the residual sodium bisulfite and acetone sodium bisulfite precipitate to obtain the anhydrous ethanol used for medicine and used for removing organic impurities.
Example 3
Adding 1L of absolute ethyl alcohol into a 5L three-necked bottle, adding 10g of calcium peroxide, heating to 80 ℃, refluxing for 4h, and removing the residual calcium peroxide to obtain absolute ethyl alcohol in the first stage;
adding 0.8g of potassium hydroxide into the absolute ethyl alcohol in the first stage, reacting for 5 hours at room temperature, and filtering to remove the residual potassium hydroxide to obtain the absolute ethyl alcohol in the second stage;
adding 2g of calcium hydroxide into the anhydrous ethanol in the second stage, heating to 50 ℃, stirring for 8 hours, and filtering to remove the residual calcium hydroxide to obtain the anhydrous ethanol in the third stage;
adding 20g of sodium bisulfite solid into the anhydrous ethanol in the third stage, stirring at 40 deg.C or below for 12h, filtering, and removing the residual sodium bisulfite and acetone sodium bisulfite precipitate to obtain the anhydrous ethanol for medicine use with organic impurities removed.
The results of gas chromatography of absolute ethanol in each of examples 2 to 3 were the same as in examples, in which methanol and isopropanol were removed in the first stage, acetaldehyde and acetal produced in the first stage were removed in the second stage, acetaldehyde was removed in the third stage, and acetone was removed in the fourth stage. Therefore, the method provided by the invention can be deduced to completely remove organic impurities such as acetaldehyde, acetal, methanol, acetone, isopropanol and the like in the medicinal anhydrous ethanol.
Although the present invention has been described in detail with reference to the foregoing embodiments, it should be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (10)
1. An impurity removal method for organic impurities in absolute ethyl alcohol is characterized by comprising the following steps:
adding calcium peroxide into absolute ethyl alcohol, heating, refluxing and filtering to obtain absolute ethyl alcohol in the first stage;
adding strong base into the absolute ethyl alcohol in the first stage, reacting at room temperature, and filtering to obtain absolute ethyl alcohol in the second stage;
adding weak base into the anhydrous ethanol of the second stage, heating, stirring, reacting, and filtering to obtain anhydrous ethanol of the third stage;
and adding sodium bisulfite solid into the absolute ethyl alcohol in the third stage, heating, stirring, reacting, and filtering to obtain the absolute ethyl alcohol with organic impurities removed.
2. The method for removing organic impurities from absolute ethanol according to claim 1,
the heating reflux condition is heating to 70-80 ℃ for reflux for 1-4 h.
3. The method of claim 1, wherein the method comprises the steps of,
the addition amount of the calcium peroxide is 3-10 per mill of the mass of the absolute ethyl alcohol.
4. The method for removing organic impurities from absolute ethanol according to claim 1,
the reaction time is 3-5h at room temperature.
5. The method of claim 1, wherein the method comprises the steps of,
the strong base comprises one of potassium hydroxide or sodium hydroxide, and the addition amount of the strong base is 3-10 per mill of the mass of the absolute ethyl alcohol.
6. The method for removing organic impurities from absolute ethanol according to claim 1,
the heating and stirring conditions of the second stage are heating to 40-50 ℃ and stirring for 2-8 h.
7. The method for removing organic impurities from absolute ethanol according to claim 1,
the weak base comprises one of calcium hydroxide or aluminum hydroxide; the addition amount of the weak base is 0.5-5% of the mass of the absolute ethyl alcohol.
8. The method for removing organic impurities from absolute ethanol according to claim 1,
the heating and stirring condition of the third stage is 10-40 ℃ and 4-12 h.
9. The method of claim 1, wherein the method comprises the steps of,
the adding amount of the sodium bisulfite is 1 to 5 percent of the mass of the absolute ethyl alcohol.
10. The method for removing organic impurities from anhydrous ethanol according to any one of claims 1 to 9,
the organic impurities in the absolute ethyl alcohol comprise acetaldehyde, methanol, acetone and isopropanol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210840201.7A CN115340444B (en) | 2022-07-15 | 2022-07-15 | Impurity removing method for organic impurities in absolute ethyl alcohol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210840201.7A CN115340444B (en) | 2022-07-15 | 2022-07-15 | Impurity removing method for organic impurities in absolute ethyl alcohol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115340444A true CN115340444A (en) | 2022-11-15 |
| CN115340444B CN115340444B (en) | 2024-06-07 |
Family
ID=83949893
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210840201.7A Active CN115340444B (en) | 2022-07-15 | 2022-07-15 | Impurity removing method for organic impurities in absolute ethyl alcohol |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115340444B (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1166920A (en) * | 1967-02-20 | 1969-10-15 | Toyo Koatsu Ind Inc | Method of refining ethanol |
| CN102432427A (en) * | 2011-11-10 | 2012-05-02 | 国药集团国瑞药业有限公司 | Preparation method of medicinal absolute ethyl alcohol |
| CN106397127A (en) * | 2016-08-30 | 2017-02-15 | 蚌埠丰原医药科技发展有限公司 | Preparation method of chromatographic pure methanol for scientific research by using industrial grade methanol |
| CN108264498A (en) * | 2017-08-16 | 2018-07-10 | 石家庄诚志永华显示材料有限公司 | Compound, the liquid crystal media comprising the compound and its application |
| CN110759319A (en) * | 2019-10-25 | 2020-02-07 | 华东理工大学 | Slow-release nano calcium peroxide material, preparation method thereof and method for removing chlorohydrocarbon and/or benzene series in underground water by using slow-release nano calcium peroxide material |
| CN111269088A (en) * | 2020-03-10 | 2020-06-12 | 上海得幸能源科技有限公司 | Preparation method of anhydrous ethanol for medicine |
-
2022
- 2022-07-15 CN CN202210840201.7A patent/CN115340444B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1166920A (en) * | 1967-02-20 | 1969-10-15 | Toyo Koatsu Ind Inc | Method of refining ethanol |
| CN102432427A (en) * | 2011-11-10 | 2012-05-02 | 国药集团国瑞药业有限公司 | Preparation method of medicinal absolute ethyl alcohol |
| CN106397127A (en) * | 2016-08-30 | 2017-02-15 | 蚌埠丰原医药科技发展有限公司 | Preparation method of chromatographic pure methanol for scientific research by using industrial grade methanol |
| CN108264498A (en) * | 2017-08-16 | 2018-07-10 | 石家庄诚志永华显示材料有限公司 | Compound, the liquid crystal media comprising the compound and its application |
| CN110759319A (en) * | 2019-10-25 | 2020-02-07 | 华东理工大学 | Slow-release nano calcium peroxide material, preparation method thereof and method for removing chlorohydrocarbon and/or benzene series in underground water by using slow-release nano calcium peroxide material |
| CN111269088A (en) * | 2020-03-10 | 2020-06-12 | 上海得幸能源科技有限公司 | Preparation method of anhydrous ethanol for medicine |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115340444B (en) | 2024-06-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102617527A (en) | Method for preparing potassium dehydroandrographolide succinate or potassium sodium dehydroandroan drographolide succinate | |
| CN115340444A (en) | Impurity removal method for organic impurities in absolute ethyl alcohol | |
| CN114366761A (en) | Preparation method of ginkgo leaf extract rich in organic acid | |
| CN102070539B (en) | 1-oxo-2-methyl-3-(1-ethoxyl)-quinoxaline and preparation method and application thereof | |
| CN112933145A (en) | Preparation method and medical application of extract of radix aconiti reduced total alkali | |
| CN112851512A (en) | Chlorogenic acid derivative for clearing away heat and toxic materials and preparation method thereof | |
| CN101113132B (en) | Method for preparing high-purity hypocrellin B | |
| CN115894418B (en) | Mongolian artelactone A-F and pharmaceutical composition thereof, and preparation method and application thereof | |
| CN104447775B (en) | A kind of new alkaloid compound, pharmaceutical composition and its medical usage | |
| CN101396373B (en) | Cinobufacini extract and preparation method thereof | |
| CN107929750B (en) | Anti-tumor pharmaceutical composition and preparation method and application thereof | |
| CN113150052B (en) | Method for purifying quercetin glycoside in pepperweed seed | |
| CN112279841A (en) | Antiviral andrographolide derivative and preparation method thereof | |
| CN104926710B (en) | Carbazochrome Sodium Sulfonate and its preparation method | |
| CN109925342B (en) | New application of phlegm-heat clearing medicine in preparation of brain glioma treatment medicine | |
| CN103301468A (en) | High-content luteolin composition | |
| CN112858534A (en) | HPLC detection method for baroxavir ester intermediate and related substances thereof | |
| CN103159710B (en) | Antiviral decalin derivate | |
| CN101747153B (en) | Inula salsoloides extract and extraction method and usage thereof | |
| CN112250728A (en) | Antiviral ursolic acid derivative and preparation method thereof | |
| CN102584915B (en) | Aromatic acid compound and application | |
| CN102070540A (en) | 1-oxygen-2-(1-ethoxy)-3-methyl-quinoxaline, and preparation method and application thereof | |
| CN109020796B (en) | Method for extracting cinnamaldehyde from cinnamon oil | |
| CN114886815B (en) | Method for extracting purely natural allergy-relieving anti-aging component from centella asiatica | |
| CN115403544B (en) | Preparation method of salvianolic acid C |
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 | ||
| GR01 | Patent grant |