CN113929595A - Preparation method of 2, 6-difluorobenzonitrile - Google Patents
Preparation method of 2, 6-difluorobenzonitrile Download PDFInfo
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- CN113929595A CN113929595A CN202111342551.2A CN202111342551A CN113929595A CN 113929595 A CN113929595 A CN 113929595A CN 202111342551 A CN202111342551 A CN 202111342551A CN 113929595 A CN113929595 A CN 113929595A
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- boiling
- polar aprotic
- aprotic solvent
- difluorobenzonitrile
- desolventizing
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- BNBRIFIJRKJGEI-UHFFFAOYSA-N 2,6-difluorobenzonitrile Chemical compound FC1=CC=CC(F)=C1C#N BNBRIFIJRKJGEI-UHFFFAOYSA-N 0.000 title claims abstract description 79
- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims abstract description 56
- 239000003880 polar aprotic solvent Substances 0.000 claims abstract description 39
- 239000011698 potassium fluoride Substances 0.000 claims abstract description 28
- 235000003270 potassium fluoride Nutrition 0.000 claims abstract description 28
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims abstract description 22
- 239000002904 solvent Substances 0.000 claims abstract description 18
- YOYAIZYFCNQIRF-UHFFFAOYSA-N 2,6-dichlorobenzonitrile Chemical compound ClC1=CC=CC(Cl)=C1C#N YOYAIZYFCNQIRF-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000007788 liquid Substances 0.000 claims abstract description 16
- 239000011259 mixed solution Substances 0.000 claims abstract description 16
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 15
- 235000011164 potassium chloride Nutrition 0.000 claims abstract description 11
- 239000001103 potassium chloride Substances 0.000 claims abstract description 11
- 238000004321 preservation Methods 0.000 claims abstract description 10
- 238000002156 mixing Methods 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims description 44
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 24
- 230000008569 process Effects 0.000 claims description 24
- 239000000706 filtrate Substances 0.000 claims description 23
- 238000009835 boiling Methods 0.000 claims description 19
- 238000001914 filtration Methods 0.000 claims description 18
- 238000010992 reflux Methods 0.000 claims description 17
- 239000012266 salt solution Substances 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 11
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 claims description 10
- 239000012065 filter cake Substances 0.000 claims description 10
- 238000005406 washing Methods 0.000 claims description 10
- 238000001816 cooling Methods 0.000 claims description 9
- 238000004821 distillation Methods 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000013078 crystal Substances 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 238000001694 spray drying Methods 0.000 claims description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 abstract description 12
- 238000009776 industrial production Methods 0.000 abstract description 7
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000000047 product Substances 0.000 description 12
- 238000011084 recovery Methods 0.000 description 12
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 6
- AVRQBXVUUXHRMY-UHFFFAOYSA-N 2,6-difluorobenzamide Chemical compound NC(=O)C1=C(F)C=CC=C1F AVRQBXVUUXHRMY-UHFFFAOYSA-N 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- BRCVOCMSJCGQNR-UHFFFAOYSA-N 2-chloro-4,6-difluorobenzonitrile Chemical compound FC1=CC(F)=C(C#N)C(Cl)=C1 BRCVOCMSJCGQNR-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical group 0.000 description 2
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- ONOTYLMNTZNAQZ-UHFFFAOYSA-N 2,6-difluorobenzoic acid Chemical compound OC(=O)C1=C(F)C=CC=C1F ONOTYLMNTZNAQZ-UHFFFAOYSA-N 0.000 description 1
- KGGHWIKBOIQEAJ-UHFFFAOYSA-N 2-fluorobenzamide Chemical compound NC(=O)C1=CC=CC=C1F KGGHWIKBOIQEAJ-UHFFFAOYSA-N 0.000 description 1
- MEXZWCMSSRGEOY-UHFFFAOYSA-N CC1C(Cl)=CC=CC1(C#N)Cl Chemical compound CC1C(Cl)=CC=CC1(C#N)Cl MEXZWCMSSRGEOY-UHFFFAOYSA-N 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 239000005893 Diflubenzuron Substances 0.000 description 1
- HRYILSDLIGTCOP-UHFFFAOYSA-N N-benzoylurea Chemical class NC(=O)NC(=O)C1=CC=CC=C1 HRYILSDLIGTCOP-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 229910001515 alkali metal fluoride Inorganic materials 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- UISUNVFOGSJSKD-UHFFFAOYSA-N chlorfluazuron Chemical compound FC1=CC=CC(F)=C1C(=O)NC(=O)NC(C=C1Cl)=CC(Cl)=C1OC1=NC=C(C(F)(F)F)C=C1Cl UISUNVFOGSJSKD-UHFFFAOYSA-N 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- QQQYTWIFVNKMRW-UHFFFAOYSA-N diflubenzuron Chemical compound FC1=CC=CC(F)=C1C(=O)NC(=O)NC1=CC=C(Cl)C=C1 QQQYTWIFVNKMRW-UHFFFAOYSA-N 0.000 description 1
- 229940019503 diflubenzuron Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- RYLHNOVXKPXDIP-UHFFFAOYSA-N flufenoxuron Chemical compound C=1C=C(NC(=O)NC(=O)C=2C(=CC=CC=2F)F)C(F)=CC=1OC1=CC=C(C(F)(F)F)C=C1Cl RYLHNOVXKPXDIP-UHFFFAOYSA-N 0.000 description 1
- 150000004673 fluoride salts Chemical class 0.000 description 1
- RGNPBRKPHBKNKX-UHFFFAOYSA-N hexaflumuron Chemical compound C1=C(Cl)C(OC(F)(F)C(F)F)=C(Cl)C=C1NC(=O)NC(=O)C1=C(F)C=CC=C1F RGNPBRKPHBKNKX-UHFFFAOYSA-N 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01D—COMPOUNDS OF ALKALI METALS, i.e. LITHIUM, SODIUM, POTASSIUM, RUBIDIUM, CAESIUM, OR FRANCIUM
- C01D3/00—Halides of sodium, potassium or alkali metals in general
- C01D3/02—Fluorides
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01D—COMPOUNDS OF ALKALI METALS, i.e. LITHIUM, SODIUM, POTASSIUM, RUBIDIUM, CAESIUM, OR FRANCIUM
- C01D3/00—Halides of sodium, potassium or alkali metals in general
- C01D3/04—Chlorides
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01D—COMPOUNDS OF ALKALI METALS, i.e. LITHIUM, SODIUM, POTASSIUM, RUBIDIUM, CAESIUM, OR FRANCIUM
- C01D3/00—Halides of sodium, potassium or alkali metals in general
- C01D3/14—Purification
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of 2, 6-difluorobenzonitrile, which comprises the following steps: (1) mixing a high-boiling-point polar aprotic solvent and potassium fluoride, and performing desolventizing and dewatering under negative pressure to obtain a dewatering reagent and a mixed solution; (2) distilling the mixed solution obtained in the step (1) to obtain a recoverable solvent; (3) adding a high-boiling-point polar aprotic solvent into the desolventizing and dehydrating reagent obtained in the step (1), adding 2, 6-dichlorobenzonitrile under stirring, and sequentially performing heat preservation treatment and rectification treatment to obtain 2, 6-difluorobenzonitrile and residue at the bottom of a kettle; (4) and (4) post-treating the kettle bottom residual liquid obtained in the step (3) to obtain a high-boiling-point polar aprotic solvent and potassium chloride. The preparation method does not need to use a catalyst, simplifies the operation steps, saves the cost and is convenient for industrial production.
Description
Technical Field
The invention belongs to the technical field of fine chemical engineering, and particularly relates to a preparation method of 2, 6-difluorobenzonitrile.
Background
The 2, 6-Difluorobenzonitrile (DFBN) and the 2, 6-difluorobenzamide and the 2, 6-difluorobenzoic acid derived from the DFBN are key intermediates for synthesizing various fluorobenzamide urea-containing insecticides such as hexaflumuron, diflubenzuron, chlorfluazuron, flufenoxuron and the like, the benzoylurea compounds play a role by inhibiting the synthesis of chitin, have strong selectivity, small use amount, no harm to human and environmental friendliness, are known as '21 century green pesticide', have wide application value, and meanwhile, the 2, 6-difluorobenzonitrile can also be used for synthesizing medicaments and liquid crystal materials. Therefore, the 2, 6-difluorobenzonitrile has wide market prospect.
At present, the preparation method of 2, 6-difluorobenzonitrile is mainly a halogen exchange method, namely 2, 6-dichlorobenzonitrile and hydrogen fluoride or fluoride salt are subjected to a halogen exchange reaction to prepare the 2, 6-difluorobenzonitrile.
CN 104788341a discloses a method for preparing 2, 6-difluorobenzonitrile, which comprises the following steps: (1) sequentially adding an aprotic strong polar solvent, toluene, 2, 6-dichlorobenzonitrile and a catalyst (N-alkyl pyridine quaternary ammonium salt) into a reaction vessel; (2) starting a heating system, controlling the temperature of the reaction container to be 110-150 ℃, and performing reflux dehydration and toluene removal; (3) cooling the temperature of the reaction container to 90-100 ℃ by using a cooling system, and adding potassium fluoride into the reaction container; (4) starting a heating system, controlling the temperature of the reaction container to be 150-; (5) reducing the temperature of the reaction container to below 50 ℃ by using a cooling system, and performing suction filtration; (6) transferring the filtrate obtained by suction filtration into a rectifying bottle, starting a vacuum pump, collecting 105-DEG C and 105-DEG C fractions to obtain a finished product of 2, 6-difluorobenzonitrile, wherein the vacuum degree is-0.1 MPa. Although the catalyst used in this patent document can reduce the activation energy of the reaction, it is difficult to recover, the post-treatment is complicated, and the quaternary ammonium salt of N-alkylpyridine has high cost and toxicity, which increases the production cost of 2, 6-difluorobenzonitrile.
CN 101456827A discloses an industrial production method of 2, 6-difluorobenzonitrile, which takes 2, 6-dichlorobenzonitrile as a raw material and potassium fluoride as alkali metal fluoride to synthesize the 2, 6-difluorobenzonitrile in the presence of a solvent and a catalyst. Wherein the solvent is anhydrous N, N-dimethyl amide, the catalyst is quaternary ammonium salt, and the prepared 2, 6-difluorobenzonitrile needs to be rectified. The anhydrous N, N-dimethyl amide adopted by the patent has certain toxicity and is difficult to recycle. In addition, quaternary ammonium salt is still used as a catalyst in the production process, and has the defects of high cost and high toxicity.
CN 112851539a discloses a preparation method of 2, 6-difluorobenzamide, which comprises the following steps: (1) reacting 2, 6-dichlorotolunitrile with hydrogen fluoride in an organic solvent to obtain 2, 6-difluorobenzonitrile; (2) and hydrolyzing the 2, 6-difluorobenzonitrile to obtain the 2, 6-difluorobenzamide. The method used in the patent uses hydrofluoric acid with strong corrosivity, the production risk coefficient is high, and the hydrofluoric acid is not easy to store, so the preparation difficulty is increased.
In summary, the raw materials adopted in the current method for preparing 2, 6-difluorobenzonitrile all contain a catalyst (quaternary ammonium salt), and although the presence of the catalyst can reduce the reaction activation energy, the quaternary ammonium salt has strong toxicity and high cost. The adoption of the quaternary ammonium salt for preparing the 2, 6-difluorobenzonitrile increases the production cost and is not beneficial to industrial production. Therefore, it is necessary to provide a method for preparing 2, 6-difluorobenzonitrile without adding a catalyst, so as to reduce the production cost and realize industrial production.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide the preparation method of the 2, 6-difluorobenzonitrile, which has the advantages of simple operation, short reaction time, no need of using a catalyst and convenience for industrial production.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides a preparation method of 2, 6-difluorobenzonitrile, which comprises the following steps:
(1) mixing a high-boiling-point polar aprotic solvent and potassium fluoride, and performing desolventizing and dewatering under negative pressure to obtain a desolventizing and dewatering reagent and a mixed solution;
(2) distilling the mixed solution obtained in the step (1) to obtain a recoverable solvent;
(3) adding a high-boiling-point polar aprotic solvent into the desolventizing and dehydrating reagent obtained in the step (1), adding 2, 6-dichlorobenzonitrile under a stirring condition, and sequentially performing heat preservation treatment and rectification treatment to obtain 2, 6-difluorobenzonitrile and residue at the bottom of a kettle;
(4) and (4) post-treating the kettle bottom residual liquid obtained in the step (3) to obtain a high-boiling-point polar aprotic solvent and potassium chloride.
The reaction substrate potassium fluoride used in the preparation method provided by the invention is very easy to absorb water in the daily storage process, so that the reaction efficiency is influenced, and therefore, in the preparation method provided by the invention, the water absorbed in the potassium fluoride is removed in the desolventizing and dewatering process in the step (1). The desolventizing and dehydrating reagent obtained in the step (1) is a mixed solution of a high-boiling-point polar aprotic solvent and potassium fluoride, and the obtained mixed solution is a mixed solution of the high-boiling-point polar aprotic solvent and water.
In the desolventizing and dewatering process in the step (1), a part of the high-boiling polar aprotic solvent is removed besides the moisture in the potassium fluoride, so that the amount of the high-boiling polar aprotic solvent in the reaction system is reduced, and the lost high-boiling polar aprotic solvent needs to be supplemented into the reaction system (namely, the supplemented high-boiling polar aprotic solvent in the step (3)).
The high boiling point polar aprotic solvents used in step (1) and step (3) of the present invention are the same batch of high boiling point polar aprotic solvents.
The kettle bottom waste liquid obtained in the step (3) of the invention contains a large amount of polar aprotic solvents with high boiling points, and the polar aprotic solvents with high boiling points (namely the polar aprotic solvents with high boiling points obtained in the step (4)) which are extracted by post-treatment have high purity can be repeatedly used in the preparation method provided by the invention, so that the production cost is saved, and the generation of three wastes is reduced.
Preferably, the high boiling polar aprotic solvent comprises any one or a combination of at least two of sulfolane, 1,3 dimethyl-2-imidazolidinone, or N-methylpyrrolidone, typical but non-limiting combinations include a combination of sulfolane and 1,3 dimethyl-2-imidazolidinone, a combination of sulfolane and N-methylpyrrolidone, a combination of 1,3 dimethyl-2-imidazolidinone and N-methylpyrrolidone, or a combination of sulfolane, 1,3 dimethyl-2-imidazolidinone, and N-methylpyrrolidone.
Preferably, the negative pressure in step (1) is 0.08-0.1MPa, such as 0.08MPa, 0.085MPa, 0.09MPa, 0.095MPa or 0.1MPa, but not limited to the values listed, and other values not listed in the range of values are equally applicable.
Preferably, the desolventizing and dehydrating reagent of step (1) has a water content of 0.5 wt.% or less, for example, 0.5 wt.%, 0.45 wt.%, 0.4 wt.%, 0.35 wt.%, or 0.3 wt.%, but not limited to the recited values, and other values not recited in the numerical ranges are also applicable; preferably 0.2 wt% or less.
Preferably, the distillation temperature in step (2) is 180-230 ℃, such as 180 ℃, 190 ℃, 200 ℃, 210 ℃, 220 ℃ or 230 ℃, but not limited to the recited values, and other unrecited values within the range of values are equally applicable.
Preferably, the distillation time in step (2) is 1 to 3 hours, for example, 1 hour, 1.4 hours, 1.8 hours, 2.2 hours, 2.6 hours or 3 hours, but not limited to the recited values, and other values not recited in the numerical range are also applicable.
Preferably, the quality of the high-boiling polar aprotic solvent of step (3) is the same as the quality of the recoverable solvent obtained in step (2).
Preferably, the molar ratio of the 2, 6-dichlorobenzonitrile from step (3) to the potassium fluoride from step (1) is 1 (2.0 to 4.0), which may be, for example, 1:2.0, 1:2.5, 1:3.0, 1:3.5 or 1.4.0, but is not limited to the values recited, and other values not recited in the range of values are equally applicable; preferably 1 (2.3-3.0).
Preferably, the mass ratio of the 2, 6-dichlorobenzonitrile in step (3) to the high-boiling polar aprotic solvent in step (1) is 1 (2.3 to 5.0), which may be, for example, 1:2.3, 1:2.5, 1:3.0, 1:3.5, 1:4.0, 1:4.5 or 1:5.0, but is not limited to the recited values, and other values not recited within the range of values are equally applicable; preferably 1 (2.5-4.0).
Preferably, the temperature of the heat preservation treatment in the step (3) is 190-; preferably 200-230 ℃.
Preferably, the incubation time in step (3) is 1-5h, for example 1h, 2h, 3h, 4h or 5h, but not limited to the recited values, and other values not recited in the range of values are also applicable.
According to the invention, the impurity content in the 2, 6-difluorobenzonitrile product can be increased due to the overhigh heat preservation temperature, and the purity of the 2, 6-difluorobenzonitrile is reduced; if the heat preservation temperature is too low, the conversion efficiency of the reaction is influenced, and the yield of the product is influenced.
Preferably, the rectification process in step (3) comprises a total reflux and a fraction collection process which are sequentially carried out.
Preferably, the vacuum degree in the system before the total reflux is 0.05 to 0.09MPa, such as 0.05MPa, 0.06MPa, 0.07MPa, 0.08MPa or 0.09MPa, but not limited to the enumerated values, and other values in the numerical range are also applicable; preferably 0.07-0.09 MPa.
Preferably, the total reflux time is 2 to 5 hours, for example, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours or 5 hours, but not limited to the recited values, and other values not recited in the numerical range are also applicable.
Preferably, the reflux ratio during the fraction collection is 20 (2-10), which may be, for example, 20:2, 20:3, 20:4, 20:5, 20:6, 20:7, 20:8, 20:9, or 20:10, but is not limited to the recited values, and other values not recited in the numerical range are equally applicable; preferably 20 (2-6).
Preferably, the end point of the distillate collection process is 100 ℃ or less, and may be, for example, 100 ℃, 95 ℃, 90 ℃, 85 ℃, 80 ℃, 75 ℃ or 70 ℃, but is not limited to the recited values, and other values not recited in the numerical ranges are equally applicable.
Preferably, the post-processing of step (4) comprises the steps of:
(a) sequentially filtering, washing, hot dissolving, adsorbing and decoloring the kettle bottom residual liquid obtained in the step (3) and filtering to obtain a salt solution;
(b) sequentially cooling, crystallizing and filtering the salt solution obtained in the step (a) to obtain potassium chloride crystals and filtrate;
(c) and (c) carrying out spray drying on the filtrate obtained in the step (b) to obtain the potassium fluoride.
Preferably, the washing liquid used in the washing process of step (a) comprises toluene.
As a preferable technical scheme, the preparation method of the 2, 6-difluorobenzonitrile provided by the invention comprises the following steps:
(1) mixing a high-boiling-point polar aprotic solvent and potassium fluoride, and performing desolventizing and dewatering under the negative pressure of 0.08-0.1MPa to obtain a desolventizing and dewatering reagent and a mixed solution;
(2) distilling the mixed solution obtained in the step (1) at the temperature of 190 ℃ and 230 ℃ for 1-3h to obtain a recyclable solvent;
(3) adding a boiling point polar aprotic solvent into the desolventizing and dehydrating reagent obtained in the step (1), adding 2, 6-dichlorobenzonitrile under the stirring condition, heating to 190-; the molar ratio of the 2, 6-dichlorobenzonitrile to the potassium fluoride is 1 (2.0-4.0); the mass ratio of the 6-dichlorobenzonitrile to the high-boiling polar aprotic solvent in the step (1) is 1 (2.3-5.0);
(4) post-treating the kettle bottom residual liquid obtained in the step (3) to obtain a high-boiling-point polar aprotic solvent and potassium chloride;
carrying out the post-treatment in the step (4) by adopting the following steps:
(a) filtering the residual liquid at the bottom of the kettle obtained in the step (3) to obtain filtrate and filter cakes;
(b) distilling the filtrate obtained in the step (a) under negative pressure to obtain a high-boiling-point polar aprotic solvent;
(c) washing the filter cake obtained in the step (a) with toluene, thermally dissolving, adsorbing and decolorizing, and filtering to obtain a salt solution;
(d) sequentially cooling, crystallizing and filtering the salt solution obtained in the step (c) to obtain potassium chloride crystals and filtrate; and (4) spray-drying the obtained filtrate to obtain the potassium fluoride.
The recitation of numerical ranges herein includes not only the above-recited numerical values, but also any numerical values between non-recited numerical ranges, and is not intended to be exhaustive or to limit the invention to the precise numerical values encompassed within the range for brevity and clarity.
Compared with the prior art, the invention has the beneficial effects that:
(1) the preparation method of the 2, 6-difluorobenzonitrile provided by the invention does not need to use a catalyst, simplifies the operation steps, saves the cost and is convenient for industrial production;
(2) the recyclable solvent and the potassium fluoride obtained in the preparation method of the 2, 6-difluorobenzonitrile can be reused for multiple times, so that the production cost is saved, and the generation of three wastes is reduced;
(3) the recovery rate of the 2, 6-difluorobenzonitrile prepared by the preparation method of the 2, 6-difluorobenzonitrile provided by the invention can reach 98.7%, and the purity is more than 99.2%.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.
Example 1
The embodiment provides a preparation method of 2, 6-difluorobenzonitrile, which includes the following steps:
(1) 560g of 1, 3-dimethyl-2-imidazolidinone and 133.6g of potassium fluoride are mixed, and desolventizing and dehydrating are carried out under the negative pressure of 0.1MPa to obtain a desolventizing and dehydrating reagent and a mixed solution;
(2) distilling the mixed solution obtained in the step (1) at the temperature of 210 ℃ for 2h to obtain a recoverable solvent;
(3) supplementing 1, 3-dimethyl-2-imidazolidinone into the desolventizing and dehydrating reagent obtained in the step (1), adding 172g of 2, 6-dichlorobenzonitrile under stirring, heating to 210 ℃, carrying out heat preservation treatment for 2 hours, adjusting the vacuum degree of a system to be 0.07-0.08MPa to total reflux, collecting fractions at a reflux ratio of 20:2 after the total reflux is carried out for 3 hours, and obtaining 2, 6-difluorobenzonitrile and residue at the bottom of a kettle until the temperature of the top of the tower is less than or equal to 100 ℃; the mass of the 1, 3-dimethyl-2-imidazolidinone is the same as that of the recoverable solvent obtained in the step (2);
(4) post-treating the residual liquid at the bottom of the kettle obtained in the step (3);
carrying out the post-treatment in the step (4) by adopting the following steps:
(a) filtering the residual liquid at the bottom of the kettle obtained in the step (3) to obtain filtrate and filter cakes;
(b) distilling the filtrate obtained in the step (a) under negative pressure to obtain a high-boiling-point polar aprotic solvent;
(c) washing the filter cake obtained in the step (a) with toluene, thermally dissolving, adsorbing and decolorizing, and filtering to obtain a salt solution;
(d) sequentially cooling, crystallizing and filtering the salt solution obtained in the step (c) to obtain potassium chloride crystals and filtrate; and (4) spray-drying the obtained filtrate to obtain the potassium fluoride.
136.9g of 2, 6-difluorobenzonitrile were prepared by the method for preparing 2, 6-difluorobenzonitrile provided in this example.
Example 2
This example provides a process for producing 2, 6-difluorobenzonitrile, which is the same as in example 1 except that 560g of 1, 3-dimethyl-2-imidazolidinone in step (1) is replaced with 575g of sulfolane and dimethyl-2-imidazolidinone in step (3) is replaced with sulfolane.
137.3g of 2, 6-difluorobenzonitrile was prepared by the method for preparing 2, 6-difluorobenzonitrile provided in this example.
Example 3
This example provides a process for producing 2, 6-difluorobenzonitrile, which is the same as in example 2, except that the sulfolane of step (1) is replaced with a once-recovered sulfolane of equal mass, and the sulfolane of step (3) is replaced with a once-recovered sulfolane.
The sulfolane obtained by one-time recovery in this example is a recoverable solvent obtained by one-time distillation.
137.1g of 2, 6-difluorobenzonitrile was prepared by the method for preparing 2, 6-difluorobenzonitrile provided in this example.
Example 4
This example provides a process for producing 2, 6-difluorobenzonitrile, which is the same as in example 2, except that the sulfolane in step (1) is replaced with the sulfolane obtained by the secondary recovery and the sulfolane in step (3) is replaced with the sulfolane obtained by the secondary recovery.
The sulfolane obtained by the primary recovery in this example is a recoverable solvent obtained by secondary distillation.
132.4g of 2, 6-difluorobenzonitrile were obtained by the method for preparing 2, 6-difluorobenzonitrile provided in this example.
Example 5
This example provides a process for producing 2, 6-difluorobenzonitrile, which is the same as in example 2, except that the sulfolane of step (1) is replaced with the sulfolane of the same mass obtained by three times of recovery, and the sulfolane of step (3) is replaced with the sulfolane obtained by three times of recovery.
The sulfolane obtained by one-time recovery in this example is a recoverable solvent obtained by three-time distillation.
132g of 2, 6-difluorobenzonitrile was prepared by the method for preparing 2, 6-difluorobenzonitrile provided in this example.
Example 6
This example provides a process for producing 2, 6-difluorobenzonitrile, which is the same as in example 2, except that the sulfolane of step (1) is replaced with the sulfolane of the same mass obtained by four times of recovery, and the sulfolane of step (3) is replaced with the sulfolane obtained by four times of recovery.
The sulfolane obtained by one-time recovery in this example is a recoverable solvent obtained by four times of distillation.
109.9g of 2, 6-difluorobenzonitrile were prepared according to the preparation method of 2, 6-difluorobenzonitrile provided in this example.
Example 7
This example provides a process for producing 2, 6-difluorobenzonitrile which is the same as in example 2 except that the reflux ratio in step (3) is changed to 20: 10.
134.2g of 2, 6-difluorobenzonitrile was prepared according to the preparation method of 2, 6-difluorobenzonitrile provided in this example.
Example 8
This example provides the same process as in example 2 except that the amount of potassium fluoride used in step (1) was changed to 116.2 g.
133.3g of 2, 6-difluorobenzonitrile were prepared according to the preparation method of 2, 6-difluorobenzonitrile provided in this example.
Example 9
This example provides a process for producing 2, 6-difluorobenzonitrile, which is the same as in example 2 except that the mass of sulfolane in step (1) is changed to 340 g.
133g of 2, 6-difluorobenzonitrile was prepared by the method for preparing 2, 6-difluorobenzonitrile provided in this example.
Example 10
This example provides a process for producing 2, 6-difluorobenzonitrile, which is the same as in example 2 except that the temperature for the heat-retaining treatment in step (3) is changed to 190 ℃.
130.2g of 2, 6-difluorobenzonitrile were prepared by the method for preparing 2, 6-difluorobenzonitrile provided in this example.
Example 11
This example provides a process for producing 2, 6-difluorobenzonitrile, which is the same as in example 2 except that the temperature for the heat-retaining treatment in step (3) is changed to 230 ℃.
130.5g of 2, 6-difluorobenzonitrile were obtained by the method for preparing 2, 6-difluorobenzonitrile provided in this example.
Example 12
This example provides a process for producing 2, 6-difluorobenzonitrile, which is the same as in example 2 except that the temperature for the heat-retaining treatment in step (3) is changed to 220 ℃.
132.7g of 2, 6-difluorobenzonitrile were obtained by the method for preparing 2, 6-difluorobenzonitrile provided in this example.
Comparative example 1
This comparative example provides a method of preparing 2, 6-difluorobenzonitrile, the method comprising the steps of:
(1) mixing 575g of sulfolane, 133.6g of potassium fluoride and 172g of 2, 6-dichlorobenzonitrile, heating to 210 ℃, carrying out heat preservation treatment for 2h, adjusting the vacuum degree of the system to be 0.07-0.08MPa to total reflux, collecting fractions at a reflux ratio of 20:2 after the total reflux is carried out for 3h, and obtaining 2, 6-difluorobenzonitrile and residue at the bottom of the kettle until the temperature at the top of the tower is less than or equal to 100 ℃;
(2) post-treating the residual liquid at the bottom of the kettle obtained in the step (1);
carrying out the post-treatment in the step (2) by adopting the following steps:
(a) filtering the residual liquid at the bottom of the kettle obtained in the step (1) to obtain filtrate and filter cakes;
(b) distilling the filtrate obtained in the step (a) under negative pressure to obtain a high-boiling-point polar aprotic solvent;
(c) washing the filter cake obtained in the step (a) with toluene, thermally dissolving, adsorbing and decolorizing, and filtering to obtain a salt solution;
(d) sequentially cooling, crystallizing and filtering the salt solution obtained in the step (c) to obtain potassium chloride crystals and filtrate; and (4) spray-drying the obtained filtrate to obtain the potassium fluoride.
The mixed solution of sulfolane and potassium fluoride provided in this comparative example had a water content of 0.9 wt%.
120.3g of 2, 6-difluorobenzonitrile was prepared by the method for preparing 2, 6-difluorobenzonitrile provided by this comparison.
The yields and product purities of 2, 6-difluorobenzonitrile obtained by the preparation methods provided in examples 1 to 12 and comparative example 1 are shown in table 1.
TABLE 1
As can be seen from Table 1: as can be seen from comparative examples 2 to 6, the purity of the product prepared by the preparation method of 2, 6-difluorobenzonitrile provided in examples 2 to 6 of the present invention is above 99.5%, the yield is as high as 98%, the purity of the product after the solvent is used for three times is still above 99.5%, the yield is not less than 95%, and after the product is used for four times, the yield of the product is significantly reduced, and the purity is basically unchanged; comparing example 2 with example 7, it can be seen that lowering the reflux ratio during the rectification lowers the product yield; comparing example 2 with examples 8 to 9, it is clear that too small amounts of solvent and potassium fluoride reduce the product yield; comparing example 2 with example 10, it can be seen that the yield of the product is reduced due to the low reaction temperature; comparing example 2 with comparative example 1, it is clear that too high a water content in potassium fluoride leads to a decrease in product yield.
In conclusion, the preparation method of 2, 6-difluorobenzonitrile provided by the invention does not need to use a catalyst, simplifies the operation steps, saves the cost and is convenient for industrial production; the recovery rate of the 2, 6-difluorobenzonitrile prepared by the preparation method of the 2, 6-difluorobenzonitrile provided by the invention is up to 98.7%, and the purity is over 99.2%.
The applicant declares that the above mentioned embodiments are only examples of the present invention, and should not be construed as limiting the present invention, any modifications, equivalents, improvements, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.
Claims (10)
1. A preparation method of 2, 6-difluorobenzonitrile is characterized by comprising the following steps:
(1) mixing a high-boiling-point polar aprotic solvent and potassium fluoride, and performing desolventizing and dewatering under negative pressure to obtain a desolventizing and dewatering reagent and a mixed solution;
(2) distilling the mixed solution obtained in the step (1) to obtain a recoverable solvent;
(3) adding a high-boiling-point polar aprotic solvent into the desolventizing and dehydrating reagent obtained in the step (1), adding 2, 6-dichlorobenzonitrile under a stirring condition, and sequentially performing heat preservation treatment and rectification treatment to obtain 2, 6-difluorobenzonitrile and residue at the bottom of a kettle;
(4) and (4) post-treating the kettle bottom residual liquid obtained in the step (3) to obtain a high-boiling-point polar aprotic solvent and potassium chloride.
2. The production method according to claim 1, wherein the high-boiling polar aprotic solvent comprises any one of or a combination of at least two of sulfolane, 1,3 dimethyl-2-imidazolidinone, or N-methylpyrrolidone;
preferably, the negative pressure of the step (1) is 0.08-0.1 MPa;
preferably, the water content of the desolventizing and dehydrating reagent in the step (1) is less than or equal to 0.5 wt%, and preferably less than or equal to 0.2 wt%.
3. The method as claimed in claim 1 or 2, wherein the distillation temperature in step (2) is 180-230 ℃;
preferably, the distillation time of the step (2) is 1-3 h.
4. The process according to any one of claims 1 to 3, wherein the mass of the high-boiling polar aprotic solvent in step (3) is the same as the mass of the recoverable solvent obtained in step (2).
5. The process according to any one of claims 1 to 4, wherein the molar ratio of the 2, 6-dichlorobenzonitrile to the potassium fluoride in step (1) is 1 (2.0 to 4.0), preferably 1 (2.3 to 3.0).
6. The process according to any one of claims 1 to 5, wherein the mass ratio of the 2, 6-dichlorobenzonitrile of step (3) to the high-boiling polar aprotic solvent of step (1) is 1 (2.3 to 5.0), preferably 1 (2.5 to 4.0).
7. The method according to any one of claims 1 to 6, wherein the temperature of the heat preservation treatment in step (3) is 190-;
preferably, the time of the heat preservation treatment in the step (3) is 1-5 h.
8. The production method according to any one of claims 1 to 7, wherein the rectification treatment process of the step (3) comprises a total reflux and fraction collection process which are sequentially carried out;
preferably, the vacuum degree in the system before the total reflux is 0.05-0.09MPa, and preferably 0.07-0.09 MPa;
preferably, the time of the total reflux is 2-5 h;
preferably, the reflux ratio in the fraction collecting process is 20 (2-10), preferably 20 (2-6);
preferably, the end point of the fraction collection process is the overhead temperature ≤ 100 deg.C.
9. The production method according to any one of claims 1 to 8, wherein the post-treatment of step (4) comprises the steps of:
(a) filtering the residual liquid at the bottom of the kettle obtained in the step (3) to obtain filtrate and filter cakes;
(b) distilling the filtrate obtained in the step (a) under negative pressure to obtain a high-boiling-point polar aprotic solvent;
(c) washing, hot dissolving, adsorbing and decoloring the filter cake obtained in the step (a) in sequence, and filtering to obtain a salt solution;
(d) sequentially cooling, crystallizing and filtering the salt solution obtained in the step (c) to obtain potassium chloride crystals and filtrate; spray-drying the obtained filtrate to obtain potassium fluoride;
preferably, the washing liquid used in the washing process of step (c) comprises toluene.
10. The production method according to any one of claims 1 to 9, characterized by comprising the steps of:
(1) mixing a high-boiling-point polar aprotic solvent and potassium fluoride, and performing desolventizing and dewatering under the negative pressure of 0.08-0.1MPa to obtain a desolventizing and dewatering reagent and a mixed solution;
(2) distilling the mixed solution obtained in the step (1) at the temperature of 190 ℃ and 230 ℃ for 1-3h to obtain a recyclable solvent;
(3) adding a boiling point polar aprotic solvent into the desolventizing and dehydrating reagent obtained in the step (1), adding 2, 6-dichlorobenzonitrile under the stirring condition, heating to 190-; the molar ratio of the 2, 6-dichlorobenzonitrile to the potassium fluoride in the step (1) is 1 (2.0-4.0); the mass ratio of the 6-dichlorobenzonitrile to the high-boiling polar aprotic solvent in the step (1) is 1 (2.3-5.0);
(4) post-treating the kettle bottom residual liquid obtained in the step (3) to obtain a high-boiling-point polar aprotic solvent and potassium chloride;
carrying out the post-treatment in the step (4) by adopting the following steps:
(a) filtering the residual liquid at the bottom of the kettle obtained in the step (3) to obtain filtrate and filter cakes;
(b) distilling the filtrate obtained in the step (a) under negative pressure to obtain a high-boiling-point polar aprotic solvent;
(c) washing the filter cake obtained in the step (a) with toluene, thermally dissolving, adsorbing and decolorizing, and filtering to obtain a salt solution;
(d) sequentially cooling, crystallizing and filtering the salt solution obtained in the step (c) to obtain potassium chloride crystals and filtrate; and (4) spray-drying the obtained filtrate to obtain the potassium fluoride.
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