CN113444019A - Preparation method of N-cyanoethyl-N-acetoxyethylaniline - Google Patents
Preparation method of N-cyanoethyl-N-acetoxyethylaniline Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- RRGWFPOSTSQIQE-UHFFFAOYSA-N 2-[n-(2-cyanoethyl)anilino]ethyl acetate Chemical compound CC(=O)OCCN(CCC#N)C1=CC=CC=C1 RRGWFPOSTSQIQE-UHFFFAOYSA-N 0.000 title abstract description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 140
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims abstract description 107
- WZJJWQVBLSPALW-UHFFFAOYSA-N 3-[n-(2-hydroxyethyl)anilino]propanenitrile Chemical compound N#CCCN(CCO)C1=CC=CC=C1 WZJJWQVBLSPALW-UHFFFAOYSA-N 0.000 claims abstract description 53
- FENJKTQEFUPECW-UHFFFAOYSA-N 3-anilinopropanenitrile Chemical compound N#CCCNC1=CC=CC=C1 FENJKTQEFUPECW-UHFFFAOYSA-N 0.000 claims abstract description 39
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims abstract description 35
- 238000005886 esterification reaction Methods 0.000 claims abstract description 13
- 238000005805 hydroxylation reaction Methods 0.000 claims abstract description 11
- BZQVBRPPYCAVSE-UHFFFAOYSA-N [N-(2-cyanoethyl)-2-ethylanilino] acetate Chemical compound C(#N)CCN(C1=C(C=CC=C1)CC)OC(C)=O BZQVBRPPYCAVSE-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000010438 heat treatment Methods 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 20
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 12
- 230000035484 reaction time Effects 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 239000007789 gas Substances 0.000 claims description 5
- 239000011261 inert gas Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- -1 hydroxide N-cyanoethyl-N-hydroxyethylaniline Chemical compound 0.000 claims description 3
- 230000032050 esterification Effects 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 68
- 229960000583 acetic acid Drugs 0.000 description 42
- 239000000047 product Substances 0.000 description 28
- 238000003756 stirring Methods 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 238000001816 cooling Methods 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 230000018044 dehydration Effects 0.000 description 8
- 238000006297 dehydration reaction Methods 0.000 description 8
- 230000006196 deacetylation Effects 0.000 description 7
- 238000003381 deacetylation reaction Methods 0.000 description 7
- 239000000975 dye Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- TUXJTJITXCHUEL-UHFFFAOYSA-N disperse red 11 Chemical compound C1=CC=C2C(=O)C3=C(N)C(OC)=CC(N)=C3C(=O)C2=C1 TUXJTJITXCHUEL-UHFFFAOYSA-N 0.000 description 4
- 230000036632 reaction speed Effects 0.000 description 4
- 239000002808 molecular sieve Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- ROPYWXVRNREIQD-UHFFFAOYSA-N 2-[n-(2-cyanoethyl)-4-[(2,6-dichloro-4-nitrophenyl)diazenyl]anilino]ethyl acetate Chemical compound C1=CC(N(CCC#N)CCOC(=O)C)=CC=C1N=NC1=C(Cl)C=C([N+]([O-])=O)C=C1Cl ROPYWXVRNREIQD-UHFFFAOYSA-N 0.000 description 2
- QLRDACXDRLGLOC-UHFFFAOYSA-N 2-[n-(2-cyanoethyl)-4-[(4-nitrophenyl)diazenyl]anilino]ethyl acetate Chemical compound C1=CC(N(CCC#N)CCOC(=O)C)=CC=C1N=NC1=CC=C([N+]([O-])=O)C=C1 QLRDACXDRLGLOC-UHFFFAOYSA-N 0.000 description 2
- ZNUBBVSUTSNSIM-UHFFFAOYSA-N 2-[n-(2-cyanoethyl)-4-[(6-nitro-1,3-benzothiazol-2-yl)diazenyl]anilino]ethyl acetate Chemical compound C1=CC(N(CCC#N)CCOC(=O)C)=CC=C1N=NC1=NC2=CC=C([N+]([O-])=O)C=C2S1 ZNUBBVSUTSNSIM-UHFFFAOYSA-N 0.000 description 2
- ALLWOAVDORUJLA-UHFFFAOYSA-N Rebamipida Chemical compound C=1C(=O)NC2=CC=CC=C2C=1CC(C(=O)O)NC(=O)C1=CC=C(Cl)C=C1 ALLWOAVDORUJLA-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- IGXHOQNEKVKXSV-UHFFFAOYSA-N 2-(n-acetylanilino)ethyl acetate Chemical compound CC(=O)OCCN(C(C)=O)C1=CC=CC=C1 IGXHOQNEKVKXSV-UHFFFAOYSA-N 0.000 description 1
- LVYBYRAOZXKVCE-UHFFFAOYSA-N 2-anilinoethane-1,1-diol Chemical compound OC(O)CNC1=CC=CC=C1 LVYBYRAOZXKVCE-UHFFFAOYSA-N 0.000 description 1
- NBJDBRQLMAXNTO-UHFFFAOYSA-N N-[3-(dihydroxyamino)-4-(2-methoxyethyl)phenyl]acetamide Chemical compound CC(NC1=CC(N(O)O)=C(CCOC)C=C1)=O NBJDBRQLMAXNTO-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000000986 disperse dye Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010189 synthetic method 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of N-cyanoethyl-N-acetoxyethylaniline. The preparation method comprises the following steps: step 1), carrying out hydroxylation reaction on N-cyanoethylaniline and ethylene oxide to obtain a hydroxylate N-cyanoethyl-N-hydroxyethylaniline; and 2) carrying out esterification reaction on the hydroxylate N-cyanoethyl-N-hydroxyethylaniline and acetic anhydride and/or acetic acid to obtain an esterified product. The N-cyanoethyl-N-acetoxyl ethylaniline prepared by the preparation method has the advantages of low cost, simple steps, high yield and high purity of the obtained product, and the distilled acetic acid can be used for other reactions, thereby saving resources.
Description
Technical Field
The invention relates to a preparation method of N-cyanoethyl-N-acetoxyethylaniline, belonging to the field of dye synthesis.
Background
N-cyanoethyl-N-acetoxyethylaniline is a common dye intermediate in disperse dye synthesis, can be used as a coupling component for synthesizing C.I. disperse orange 30, C.I. disperse orange 31, C.I. disperse red 35, C.I. disperse red 72, C.I. disperse red 136, C.I. disperse red 177, C.I. disperse brown 9 and the like, and has wide application range.
The currently disclosed synthesis methods of N-cyanoethyl-N-acetoxyethylaniline are many, and Chinese patent CN106117073A discloses a synthesis method, which adopts the reaction of hydroxylate and acetic acid at the temperature of 110-140 ℃, and adds a molecular sieve in the reaction process to ensure complete reaction and simultaneously can recycle resources. However, this method increases the synthesis cost using a molecular sieve and requires activation after use of the molecular sieve, complicating the synthesis step.
Li Houkang et al, in the introduction to Romani dye production, propose a synthesis of N-cyanoethyl-N-acetoxyethylaniline, i.e. the product is obtained by reacting hydroxyethyl cyanoethylaniline with acetic anhydride at 90-92 ℃. The reaction temperature range of the method is narrow, and the method is not beneficial to control.
In the synthesis research of N-cyanoethyl-N-acetoxyethylaniline, Wang Liang mustard, et al proposed that a little concentrated sulfuric acid was used as a catalyst, and that a mixture of acetic anhydride and glacial acetic acid and N-cyanoethyl N-hydroxyethylaniline were reacted for 4 hours under heat preservation to obtain N-acetyl-N-acetoxyethylaniline. The method adopts concentrated sulfuric acid as a catalyst, and the safety is difficult to ensure.
Zhengjing et al in "Synthesis of dye intermediate N-cyanoethyl-N-acetoxyethylaniline" adopt glacial acetic acid as acylating agent, and carry out rectification reaction with raw material N-hydroxyethyl-N-cyanoethylaniline at the molar ratio of 3:1 at 140 ℃ under normal pressure for 8 hours to obtain the product N-cyanoethyl-N-acetoxyethylaniline. The method has long reaction time and is not beneficial to actual production.
Therefore, in order to solve the problems of high synthesis cost, complicated synthesis steps, long reaction time and the like, the research on a synthesis method of N-cyanoethyl-N-acetoxyethylaniline, which has the advantages of low synthesis cost, simple steps, high product purity and short reaction time, is a technical problem to be solved urgently.
Disclosure of Invention
Problems to be solved by the invention
In view of the technical problems in the prior art, the invention firstly provides a synthetic method of N-cyanoethyl-N-acetoxyl ethylaniline, which is simple and easy to operate, low in synthetic cost, short in time, high in purity of the obtained product and high in yield.
Means for solving the problems
The invention relates to a preparation method of N-cyanoethyl-N-acetoxyl ethylaniline, which comprises the following steps:
step 1), carrying out hydroxylation reaction on N-cyanoethylaniline and ethylene oxide to obtain a hydroxylate N-cyanoethyl-N-hydroxyethylaniline;
and 2) carrying out esterification reaction on the hydroxylate N-cyanoethyl-N-hydroxyethylaniline and acetic anhydride and/or acetic acid to obtain an esterified product.
The preparation method comprises the step 1), wherein the ethylene oxide is introduced and mixed with the N-cyanoethylaniline at the temperature of 60-100 ℃ and under the pressure of below 0.3 MPa.
According to the preparation method of the invention, inert gas is used for replacing air before the ethylene oxide is introduced.
The preparation method provided by the invention is characterized in that the temperature of the hydroxylation reaction is 80-95 ℃, and is preferably 85-95 ℃; the reaction time is 2-4 hours.
The preparation method according to the present invention, wherein a carboxylic acid is used as a catalyst during the hydroxylation reaction; preferably, the addition amount of the carboxylic acid is 8 to 12 percent of the mass of the N-cyanoethylaniline.
The preparation method provided by the invention is characterized in that the mass ratio of the N-cyanoethylaniline to the ethylene oxide is 2.7-3.3: 1.
The production method according to the present invention, wherein the esterification reaction is carried out by adding acetic anhydride and/or acetic acid to the hydroxide N-cyanoethyl-N-hydroxyethylaniline.
The preparation method comprises the following steps of (1) before adding acetic anhydride and/or acetic acid, controlling the temperature of a hydroxylate N-cyanoethyl-N-hydroxyethylaniline to be 80-95 ℃; and/or the presence of a gas in the gas,
before acetic anhydride and/or acetic acid are added, heating the hydroxylate N-cyanoethyl-N-hydroxyethylaniline to 100-140 ℃ to remove water and/or carboxylic acid in the hydroxylate N-cyanoethyl-N-hydroxyethylaniline.
The preparation method provided by the invention is characterized in that the esterification reaction temperature is 85-100 ℃, and the reaction time is 1.5-3.5 hours.
The preparation method comprises the step of mixing the hydroxylate N-cyanoethyl-N-hydroxyethylaniline with acetic anhydride and/or acetic acid in a mass ratio of 1.1-1.5: 1.
ADVANTAGEOUS EFFECTS OF INVENTION
The N-cyanoethyl-N-acetoxyl ethylaniline prepared by the preparation method has the advantages of low cost, simple steps, high yield and high purity of the obtained product, and the distilled acetic acid can be used for other reactions, thereby saving resources.
Detailed Description
The present invention will be described in detail below. The technical features described below are explained based on typical embodiments and specific examples of the present invention, but the present invention is not limited to these embodiments and specific examples.
Furthermore, in the following detailed description, numerous specific details are set forth in order to provide a better understanding of the present invention. It will be understood by those skilled in the art that the present invention may be practiced without some of these specific details. In other instances, methods, means, devices and steps which are well known to those skilled in the art have not been described in detail so as not to obscure the invention.
It should be noted that:
in the present specification, the numerical range represented by "numerical value a to numerical value B" means a range including the end point numerical value A, B.
All units used in the present invention are international standard units unless otherwise stated, and numerical values and numerical ranges appearing in the present invention should be understood to include errors allowed in industrial production.
In the present specification, reference to "some particular/preferred embodiments," "other particular/preferred embodiments," "embodiments," and the like, means that a particular element (e.g., feature, property, and/or characteristic) described in connection with the embodiment is included in at least one embodiment described herein, and may or may not be present in other embodiments. In addition, it is to be understood that the described elements may be combined in any suitable manner in the various embodiments.
The invention firstly provides a preparation method of N-cyanoethyl-N-acetoxyl ethylaniline, which comprises the following steps:
step 1), carrying out hydroxylation reaction on N-cyanoethylaniline and ethylene oxide to obtain a hydroxylate N-cyanoethyl-N-hydroxyethylaniline;
and 2) carrying out esterification reaction on the hydroxylate N-cyanoethyl-N-hydroxyethylaniline and acetic anhydride and/or acetic acid to obtain an esterified product.
Wherein, the reaction equation of step 1) can be
In the reaction, ethylene oxide can make N-cyanoethylaniline react to generate hydroxyl compound N-cyanoethyl-N-hydroxyethylaniline, meanwhile, the byproducts in the whole reaction process are less, and the yield and the purity of the product hydroxyl compound N-cyanoethyl-N-hydroxyethylaniline can be improved.
In step 2), the reaction equation when acetic anhydride is used may be:
the reaction equation when using acetic acid is:
in some specific embodiments, in step 1), the ethylene oxide is mixed with the cyanoethylaniline at a temperature of 60 ℃ to 100 ℃. Considering that the melting point of the N-cyanoethylaniline is 52-53 ℃, the N-cyanoethylaniline is in a molten state at the temperature of more than 60 ℃, the ethylene oxide is in a gaseous state at the temperature, and the contact area of the N-cyanoethylaniline and the ethylene oxide can be increased by introducing the ethylene oxide under the stirring state, so that the reaction is more sufficient. Specifically, the ethylene oxide and the cyanoethylaniline may be mixed by introducing the ethylene oxide at 63 ℃, 65 ℃, 67 ℃, 70 ℃, 73 ℃, 75 ℃, 78 ℃, 80 ℃, 83 ℃, 85 ℃, 88 ℃, 90 ℃, 93 ℃, 95 ℃, 98 ℃ or the like.
In some embodiments, the air is replaced with an inert gas prior to the introduction of the ethylene oxide. In the presence of air, ethylene oxide and N-cyanoethylaniline may form a wide range of explosive mixtures, and in order to ensure the safety of the reaction, the air in the apparatus is replaced by inert gas before the ethylene oxide is introduced. The inert gas may be nitrogen or the like.
Furthermore, after the ethylene oxide is introduced, the pressure in the reaction kettle is increased due to the introduction of the gas, and meanwhile, the reaction balance can be promoted to move in the positive direction by pressurizing in the reaction process, so that the reaction rate is accelerated; in addition, the rate of feeding ethylene oxide should not be too fast (i.e., the feeding time should not be too short), which may result in non-uniform pressure in the reaction vessel. Therefore, in the present invention, the pressure at which the ethylene oxide is introduced is controlled to be 0.3MPa or less, for example: 0.05MPa, 0.1MPa, 0.15MPa, 0.2MPa, 0.25MPa, 0.3MPa, etc.
In some specific embodiments, the temperature of the hydroxylation reaction is between 80 ℃ and 95 ℃, preferably between 85 ℃ and 95 ℃, for example: 82 ℃, 84 ℃, 86 ℃, 88 ℃, 90 ℃, 92 ℃, 94 ℃ and the like; the reaction time is 2-4 hours, for example: 2.3 hours, 2.5 hours, 2.8 hours, 3 hours, 3.3 hours, 3.5 hours, 3.8 hours, 4 hours, etc. When the temperature is 80-95 ℃, the N-cyanoethylaniline is in a molten state, and the contact area of the reaction of the N-cyanoethylaniline and ethylene oxide is increased; meanwhile, the ethylene oxide is in a gaseous state at the temperature of between 80 and 95 ℃, so that the effective collision times of the reaction can be increased, the reaction rate is accelerated, and the reaction time is shortened to some extent.
In some specific embodiments, during the hydroxylation reaction, carboxylic acid is used as a catalyst, preferably acetic acid is used as a catalyst, specifically, the amount of carboxylic acid added is 8% to 12% of the mass of the raw material, such as: 8.5%, 9%, 9.5%, 10%, 10.5%, 11%, 11.5%, etc.; the carboxylic acid is added as a catalyst in the hydroxylation reaction process, so that the reaction speed can be accelerated, the impurity content in the product can be reduced, the reaction time is shortened, and the yield and the purity of the product are improved.
Specifically, when the carboxylic acid is used as the catalyst, the carboxylic acid and the N-cyanoethylaniline are mixed, heated to 60-130 ℃ and kept for 0.1-2 hours, so that the N-cyanoethylaniline is completely dissolved, and then ethylene oxide is introduced to react with the N-cyanoethylaniline. Specifically, the heating temperature may be 65 ℃, 70 ℃, 80 ℃, 85 ℃, 95 ℃, 100 ℃, 105 ℃, 110 ℃, 115 ℃, 120 ℃, 125 ℃ or the like, and the holding time may be 0.3 hour, 0.5 hour, 0.8 hour, 1 hour, 1.2 hour, 1.5 hour, 1.8 hour or the like.
Further, the mass ratio of the N-cyanoethylaniline to the ethylene oxide is 2.7-3.3: 1, for example: 2.8:1, 2.9:1, 3:1, 3.1:1, 3.2:1, 3.3:1, etc. In the present invention, the ethylene oxide may be in slight excess. Under the condition of slight excess of ethylene oxide, the contact area of o-methoxy m-acetamino aniline and ethylene oxide can be increased, and the reaction speed is accelerated.
In some specific embodiments, the esterification reaction is carried out by adding acetic anhydride and/or acetic acid to the hydroxide N-cyanoethyl-N-hydroxyethylaniline. According to the invention, acetic anhydride and/or acetic acid are slowly added, and particularly, the contact area of the acetic anhydride and/or the acetic acid and the hydroxylate N-cyanoethyl-N-hydroxyethylaniline can be increased by selectively dropwise adding in the adding process, so that the hydroxylate is reacted more fully; meanwhile, the esterification reaction is endothermic reaction, the reaction process can be slow by selecting a dripping mode, the demand on heat is small, and the reaction temperature is controlled within a safe range.
Generally, the temperature of the hydroxylated N-cyanoethyl-N-hydroxyethylaniline before the acetic anhydride and/or acetic acid is added is 80 to 95 ℃, for example: 81 deg.C, 82 deg.C, 83 deg.C, 84 deg.C, 85 deg.C, 86 deg.C, 87 deg.C, 88 deg.C, 89 deg.C, 90 deg.C, 92 deg.C, 93 deg.C, 94 deg.C, etc. When the temperature of the hydroxylate N-cyanoethyl-N-hydroxyethylaniline is 80-95 ℃, part of water in the hydroxylate N-cyanoethyl-N-hydroxyethylaniline can be removed, the state of the hydroxylate N-cyanoethyl-N-hydroxyethylaniline is changed into a stirring state, the contact area between acetic acid and the hydroxylate is increased during stirring, the reaction rate is increased, the reaction can be more sufficient, the product yield is improved, and the like.
Further, in the invention, before acetic anhydride and/or acetic acid are added, the temperature of the hydroxyl compound N-cyanoethyl-N-hydroxyethylaniline can be raised to 100-140 ℃ to remove water and/or carboxylic acid in the hydroxyl compound N-cyanoethyl-N-hydroxyethylaniline, thereby facilitating esterification reaction. For example: heating to 105 deg.C, 110 deg.C, 115 deg.C, 120 deg.C, 125 deg.C, 130 deg.C, 135 deg.C, etc.
In some specific embodiments, the temperature of the esterification reaction is from 85 ℃ to 100 ℃, for example: 86 ℃, 88 ℃, 90 ℃, 92 ℃, 94 ℃, 96 ℃, 98 ℃ and the like; the reaction time is 1.5-3.5 hours, for example: 1.8 hours, 2 hours, 2.2 hours, 2.5 hours, 2.8 hours, 3 hours, 3.2 hours, etc. When the temperature of the esterification reaction is 85-100 ℃, acetic acid and/or acetic anhydride are in a liquid state, and the hydroxylate 2-methoxy-5-acetamido-N, N-dihydroxyethylaniline is in a molten state, so that the number of active molecules capable of effectively colliding with the hydroxylate and the N-dihydroxyethylaniline is large, the number of generated effective collision times is increased, and the reaction rate is increased; when the reaction time is 1.5-3.5 hours, the reaction time is controlled in the period of time, so that the reaction process can absorb heat slowly and be controlled.
Further, in the present invention, after the reaction reaches the end point, the pressure of the system is reduced to 0MPa or less, preferably-0.1 to-1.0 MPa, for example, by using a pressure reduction operation in the step 2): 0.1MPa, -0.2MPa, -0.3MPa, -0.4MPa, -0.6MPa and the like, so that part of acetic acid (acetic anhydride can generate acetic acid when meeting water) in the product is distilled out to improve the purity of the reaction product.
Further, in the invention, the mass ratio of the hydroxylate N-cyanoethyl-N-hydroxyethylaniline to acetic anhydride and/or acetic acid is about 1.1-1.5: 1. For example: 1.2:1, 1.3:1, 1.4:1, etc., under the condition of slight excess of acetic anhydride and/or acetic acid, the contact area of the hydroxyl compound N-cyanoethyl-N-hydroxyethylaniline and acetic anhydride and/or acetic acid can be increased, and the reaction speed is accelerated.
The reaction can be carried out by using acetic acid or acetic anhydride, and the reaction is preferably carried out by using acetic anhydride. When the acetic anhydride is used for reaction, the reaction activity of the acetic anhydride is stronger, the reaction speed is faster, the purity of the reaction product is higher, and the yield is also improved.
The N-cyanoethyl-N-acetoxyl ethylaniline prepared by the preparation method can be used as a dye intermediate for synthesizing dye components such as C.I. disperse orange 30, C.I. disperse orange 31, C.I. disperse red 35, C.I. disperse red 72, C.I. disperse red 136, C.I. disperse red 177, C.I. disperse brown 9 and the like.
Examples
Embodiments of the present invention will be described in detail below with reference to examples, but those skilled in the art will appreciate that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available.
Note: the raw materials used in the patent can be purchased in the market.
Example 1
(1) And (2) replacing air in the high-pressure reaction kettle by using nitrogen, continuously replacing for three times, adding 180g of N-cyanoethylaniline and 18g of 98% acetic acid in the high-pressure reaction kettle, stirring, heating to 65 ℃, and keeping the temperature for 2 hours to completely dissolve the N-cyanoethylaniline. After the N-cyanoethylaniline is completely dissolved, 58g of ethylene oxide is introduced, the temperature is controlled to be about 85 ℃ during introduction, the pressure is kept to be less than or equal to 0.3MPa, and the temperature is kept at 85 ℃ after introduction for reaction for 2.5 hours to obtain hydroxylate N-cyanoethylaniline; after the reaction, the temperature of the hydroxylate N-cyanoethyl-N-hydroxyethylaniline is about 85 ℃.
(2) Heating the hydroxylate N-cyanoethyl-N-hydroxyethylaniline obtained in the step (1) to 100 ℃, simultaneously starting stirring and vacuum dehydration and deacetylation, cooling the hydroxylate N-cyanoethyl-N-hydroxyethylaniline to 85 ℃ after the dehydration is finished, dropwise adding 170g of acetic anhydride, heating to 90 ℃ after the addition is finished, reacting for 3 hours until the reaction is finished, using pressure reduction operation to ensure that the system pressure is-0.5 MPa after the reaction is finished so as to evaporate partial acetic acid, and cooling to room temperature after the reaction is finished to obtain the product N-cyanoethyl-N-acetoxyethylaniline.
Example 2
(1) And (2) replacing air in the high-pressure reaction kettle by using nitrogen, continuously replacing for three times, adding 100g of N-cyanoethylaniline and 15g of 98% acetic acid into the high-pressure reaction kettle, stirring, heating to 85 ℃, and keeping the temperature for 1.5 hours to completely dissolve the N-cyanoethylaniline. After the N-cyanoethylaniline is completely dissolved, 35g of ethylene oxide is introduced, the temperature is controlled to be about 90 ℃ during introduction, the pressure is kept to be less than or equal to 0.3MPa, and the temperature is kept at 90 ℃ after introduction for reaction for 2 hours to obtain a hydroxylate N-cyanoethyl-N-hydroxyethylaniline; after the reaction, the temperature of the hydroxylate N-cyanoethyl-N-hydroxyethylaniline is about 90 ℃.
(2) Heating the hydroxylate N-cyanoethyl-N-hydroxyethylaniline obtained in the step (1) to 120 ℃, simultaneously starting stirring and vacuum dehydration and deacetylation, cooling the hydroxylate N-cyanoethyl-N-hydroxyethylaniline to 85 ℃ after the dehydration is finished, dropwise adding 98g of acetic anhydride, heating to 95 ℃ after the addition is finished, reacting for 2.5 hours until the reaction is finished, using a pressure reduction operation to ensure that the system pressure is-0.5 MPa so as to evaporate partial acetic acid, and cooling to room temperature after the reaction is finished to obtain the product N-cyanoethyl-N-acetoxyethylaniline.
Example 3
(1) And (2) replacing air in the high-pressure reaction kettle by using nitrogen, continuously replacing for three times, adding 100g of N-cyanoethylaniline and 15g of 98% acetic acid into the high-pressure reaction kettle, stirring, heating to 120 ℃, and keeping the temperature for 1 hour to completely dissolve the N-cyanoethylaniline. After the N-cyanoethylaniline is completely dissolved, introducing 35g of ethylene oxide, controlling the temperature at 95 ℃ and the pressure at less than or equal to 0.3MPa when introducing, and then preserving the temperature at 95 ℃ for reacting for 2 hours to obtain a hydroxylate N-cyanoethyl-N-hydroxyethylaniline; after the reaction, the temperature of the hydroxylate N-cyanoethyl-N-hydroxyethylaniline was about 95 ℃.
(2) Heating the hydroxylate N-cyanoethyl-N-hydroxyethylaniline obtained in the step (1) to 140 ℃, simultaneously starting stirring and vacuum dehydration and deacetylation, cooling the hydroxylate N-cyanoethyl-N-hydroxyethylaniline to 85 ℃ after the dehydration is finished, dropwise adding 85g of acetic anhydride, heating to 100 ℃ after the addition is finished, reacting for 1.5 hours until the reaction is finished, using a pressure reduction operation to ensure that the system pressure is-0.5 MPa after the reaction is finished so as to evaporate partial acetic acid, and cooling to room temperature after the reaction is finished to obtain the product N-cyanoethyl-N-acetoxyethylaniline.
Example 4
(1) And (2) replacing air in the high-pressure reaction kettle by using nitrogen, continuously replacing for three times, adding 100g of N-cyanoethylaniline and 15g of 98% acetic acid into the high-pressure reaction kettle, stirring, heating to 120 ℃, and keeping the temperature for 1 hour to completely dissolve the N-cyanoethylaniline. After the N-cyanoethylaniline is completely dissolved, introducing 35g of ethylene oxide, controlling the temperature at 95 ℃ and the pressure at less than or equal to 0.3MPa when introducing, and then preserving the temperature at 95 ℃ for reacting for 2 hours to obtain a hydroxylate N-cyanoethyl-N-hydroxyethylaniline; after the reaction, the temperature of the hydroxylate N-cyanoethyl-N-hydroxyethylaniline is about 95 ℃.
(2) Heating the hydroxylate N-cyanoethyl-N-hydroxyethylaniline obtained in the step (1) to 140 ℃, simultaneously starting stirring and vacuum dehydration and deacetylation, cooling the hydroxylate N-cyanoethyl-N-hydroxyethylaniline to 85 ℃ after the deacetylation is finished, dropwise adding 85g of acetic acid, heating to 100 ℃ after the addition is finished, reacting for 1.5 hours until the reaction is finished, using pressure reduction operation to ensure that the system pressure is-0.5 MPa after the reaction is finished so as to evaporate partial acetic acid, and cooling to room temperature after the reaction is finished to obtain the product N-cyanoethyl-N-acetoxyethylaniline.
Example 5
(1) And (2) replacing air in the high-pressure reaction kettle by using nitrogen, continuously replacing for three times, adding 100g of N-cyanoethylaniline and 15g of 98% acetic acid into the high-pressure reaction kettle, stirring, heating to 120 ℃, and keeping the temperature for 1 hour to completely dissolve the N-cyanoethylaniline. After the N-cyanoethylaniline is completely dissolved, introducing 35g of ethylene oxide, controlling the temperature at 95 ℃ and the pressure at less than or equal to 0.3MPa when introducing, and then preserving the temperature at 95 ℃ for reacting for 2 hours to obtain a hydroxylate N-cyanoethyl-N-hydroxyethylaniline; after the reaction, the temperature of the hydroxylate N-cyanoethyl-N-hydroxyethylaniline is about 95 ℃.
(2) Heating the hydroxylate N-cyanoethyl-N-hydroxyethylaniline obtained in the step (1) to 140 ℃, simultaneously starting stirring and vacuum dehydration and deacetylation, cooling the hydroxylate N-cyanoethyl-N-hydroxyethylaniline to 85 ℃ after the deacetylation is finished, dropwise adding 80g of acetic anhydride and 5g of acetic acid, heating to 100 ℃ after the addition is finished, reacting for 1.5 hours until the reaction is finished, evaporating partial acetic acid by using a pressure reduction operation after the reaction is finished, and cooling to room temperature after the reaction is finished to obtain the product N-cyanoethyl-N-acetoxyethylaniline.
Comparative example 1
Putting 19g of N-cyanoethyl-N-hydroxyethyl aniline and 19g of acetic anhydride into a three-necked bottle, starting stirring, heating to 100 ℃, keeping the reaction temperature at 100-105 ℃ for acetylation, cooling the materials to room temperature after 2 hours, and adding 10g of acetic acid to obtain the product N-cyanoethyl-N-acetoxyl ethyl aniline.
Comparative example 2
100g of mixed solution containing glacial acetic acid and N-cyanoethyl-N-hydroxyethylaniline (wherein the content of the glacial acetic acid is 40 percent, the content of the N-cyanoethyl-N-hydroxyethylaniline is 54.6 percent, and the balance is water) is added into a three-neck flask, stirring is started, 31g of 98 percent acetic anhydride is added, 2g of 98 percent concentrated sulfuric acid is dripped after the temperature is raised to 60 ℃, and the product N-cyanoethyl-N-acetoxyethylaniline is obtained after heat preservation reaction for 4 hours.
Comparative example 3
Putting 100g of N-hydroxyethyl-N-cyanoethylaniline and 90g of glacial acetic acid in a three-necked bottle, starting stirring, heating to 140 ℃, keeping the temperature at 140 ℃ for reacting for 8 hours, and reaching the end point to obtain the product N-cyanoethyl-N-acetoxyethylaniline.
Performance testing
1. Purity of
The purity of N-cyanoethyl-N-acetoxyethylaniline was tested by HPLC and the results are shown in Table 1.
2. Overall yield of
The total yield, which is the amount of the starting material for producing the objective product (N-cyanoethyl-N-acetoxyethylaniline)/the feed amount of the starting material × 100%, was calculated and found to be shown in table 1.
3. Retention time
The N-cyanoethyl-N-acetoxyl ethylaniline of examples 1-3 and comparative examples 1-3 were stored at normal temperature and pressure, and a sample was taken every 1 month of storage, and the product purity was tested by HPLC, and the product purity of 65% or less was regarded as expired.
TABLE 1
| Name of item | Purity (%) | Total yield (%) | Retention time |
| Example 1 | 96.2 | 97.5 | 6 months old |
| Example 2 | 96.8 | 96.8 | 6 months old |
| Example 3 | 97.0 | 98.1 | 6 months old |
| Example 4 | 95.3 | 96.7 | 6 months old |
| Example 5 | 95.8 | 96.9 | 6 months old |
| Comparative example 1 | 91.3 | 92.9 | 1 month |
| Comparative example 2 | 89.2 | 90.3 | 3 months old |
| Comparative example 3 | 92.2 | 93.9 | 3 months old |
As can be seen from Table 1, the purities of N-cyanoethyl-N-acetoxyethylaniline were higher than 95% in examples 1-5, and lower than 95% in comparative examples 1-3; and in terms of yield, the yield of N-cyanoethyl-N-acetoxyethylaniline is higher than 95% in examples 1-5, and the yield of the product is lower than 95% in comparative examples 1-3; finally, the product N-cyanoethyl-N-acetoxyethylaniline obtained by the process of examples 1-5 had a shelf life of up to 6 months, whereas the product obtained by the process of comparative examples 1-3 had a shelf life lower than that of the process of examples.
The N-cyanoethyl-N-acetoxyl ethylaniline prepared by the method has low cost and simple steps, the obtained product has the characteristics of high yield and high purity, and simultaneously, the acetic acid obtained by reduced pressure distillation can be used for other reactions, so that the resources are saved.
The above examples of the present invention are merely examples for clearly illustrating the present invention and are not intended to limit the embodiments of the present invention. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the protection scope of the claims of the present invention.
Claims (10)
1. A preparation method of N-cyanoethyl-N-acetoxyl ethylaniline is characterized by comprising the following steps:
step 1), carrying out hydroxylation reaction on N-cyanoethylaniline and ethylene oxide to obtain a hydroxylate N-cyanoethyl-N-hydroxyethylaniline;
and 2) carrying out esterification reaction on the hydroxylate N-cyanoethyl-N-hydroxyethylaniline and acetic anhydride and/or acetic acid to obtain an esterified product.
2. The method according to claim 1, wherein the ethylene oxide is introduced and mixed with the cyanoethylaniline in step 1) at a temperature of 60 to 100 ℃ and a pressure of 0.3MPa or less.
3. The process according to claim 2, wherein the air is replaced with an inert gas before the ethylene oxide is introduced.
4. The process according to any one of claims 1 to 3, wherein the temperature of the hydroxylation reaction is between 80 ℃ and 95 ℃, preferably between 85 ℃ and 95 ℃; the reaction time is 2-4 hours.
5. The production process according to any one of claims 1 to 4, wherein a carboxylic acid is used as a catalyst during the hydroxylation reaction; preferably, the addition amount of the carboxylic acid is 8 to 12 percent of the mass of the N-cyanoethylaniline.
6. The method according to any one of claims 1 to 5, wherein the mass ratio of N-cyanoethylaniline to ethylene oxide is 2.7 to 3.3: 1.
7. The process according to any one of claims 1 to 6, wherein the esterification is carried out by adding acetic anhydride and/or acetic acid to the hydroxide N-cyanoethyl-N-hydroxyethylaniline.
8. The method according to claim 7, wherein the temperature of the hydroxylated N-cyanoethyl-N-hydroxyethylaniline is 80 to 95 ℃ before the acetic anhydride and/or acetic acid are added; and/or the presence of a gas in the gas,
before acetic anhydride and/or acetic acid are added, heating the hydroxylate N-cyanoethyl-N-hydroxyethylaniline to 100-140 ℃ to remove water and/or carboxylic acid in the hydroxylate N-cyanoethyl-N-hydroxyethylaniline.
9. The method according to claim 7 or 8, wherein the esterification reaction is carried out at a temperature of 85 ℃ to 100 ℃ for 1.5 to 3.5 hours.
10. The method according to any one of claims 1 to 9, wherein the mass ratio of the hydroxylated compound cyanoethyl-hydroxyethylaniline to acetic anhydride and/or acetic acid is 1.1 to 1.5: 1.
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Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4374068A (en) * | 1981-10-15 | 1983-02-15 | Milliken Research Corporation | Process for hydroxyalkylation of cyanoethylanilines |
| CN1754920A (en) * | 2004-09-29 | 2006-04-05 | 浙江龙盛集团股份有限公司 | Production process of azoic disperse dye |
| CN101081838A (en) * | 2006-12-21 | 2007-12-05 | 浙江龙盛集团股份有限公司 | Benzo isothiazole compound, preparation and application and disperse dyes composition |
| CN103232723A (en) * | 2012-12-31 | 2013-08-07 | 上海安诺其纺织化工股份有限公司 | Easter compounds and preparation method thereof |
| CN104003899A (en) * | 2014-06-05 | 2014-08-27 | 浙江洪翔化学工业有限公司 | Synthetic method of o-methoxy-m-acetamido-N,N-phenyldiethanolamine diacetate |
| CN104710322A (en) * | 2015-02-27 | 2015-06-17 | 宜兴市中正化工有限公司 | Synthesis method of ruby esterified liquid |
| CN105481623A (en) * | 2015-12-01 | 2016-04-13 | 上海澄厚菲贸易有限公司 | Synthetic technology of hydroxyethylaniline ester (III) |
| CN106117073A (en) * | 2016-05-17 | 2016-11-16 | 浙江龙盛化工研究有限公司 | A kind of synthetic method of dyestuff intermediate esterifying liquid |
| CN106478543A (en) * | 2016-09-30 | 2017-03-08 | 浙江闰土研究院有限公司 | A kind of benzisothiazole dye monomer compound and its intermediate, preparation method and purposes |
| CN108117492A (en) * | 2017-12-20 | 2018-06-05 | 江苏远大仙乐药业有限公司 | A kind of method for preparing N- ethyl-N hydroxyethyl aniline |
| CN111072514A (en) * | 2019-12-31 | 2020-04-28 | 烟台安诺其精细化工有限公司 | Preparation method of 3-acetamido-N, N-diacetoxyethylaniline |
-
2021
- 2021-08-02 CN CN202110879690.2A patent/CN113444019A/en active Pending
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4374068A (en) * | 1981-10-15 | 1983-02-15 | Milliken Research Corporation | Process for hydroxyalkylation of cyanoethylanilines |
| CN1754920A (en) * | 2004-09-29 | 2006-04-05 | 浙江龙盛集团股份有限公司 | Production process of azoic disperse dye |
| CN101081838A (en) * | 2006-12-21 | 2007-12-05 | 浙江龙盛集团股份有限公司 | Benzo isothiazole compound, preparation and application and disperse dyes composition |
| CN103232723A (en) * | 2012-12-31 | 2013-08-07 | 上海安诺其纺织化工股份有限公司 | Easter compounds and preparation method thereof |
| CN104003899A (en) * | 2014-06-05 | 2014-08-27 | 浙江洪翔化学工业有限公司 | Synthetic method of o-methoxy-m-acetamido-N,N-phenyldiethanolamine diacetate |
| CN104710322A (en) * | 2015-02-27 | 2015-06-17 | 宜兴市中正化工有限公司 | Synthesis method of ruby esterified liquid |
| CN105481623A (en) * | 2015-12-01 | 2016-04-13 | 上海澄厚菲贸易有限公司 | Synthetic technology of hydroxyethylaniline ester (III) |
| CN106117073A (en) * | 2016-05-17 | 2016-11-16 | 浙江龙盛化工研究有限公司 | A kind of synthetic method of dyestuff intermediate esterifying liquid |
| CN106478543A (en) * | 2016-09-30 | 2017-03-08 | 浙江闰土研究院有限公司 | A kind of benzisothiazole dye monomer compound and its intermediate, preparation method and purposes |
| CN108117492A (en) * | 2017-12-20 | 2018-06-05 | 江苏远大仙乐药业有限公司 | A kind of method for preparing N- ethyl-N hydroxyethyl aniline |
| CN111072514A (en) * | 2019-12-31 | 2020-04-28 | 烟台安诺其精细化工有限公司 | Preparation method of 3-acetamido-N, N-diacetoxyethylaniline |
Non-Patent Citations (1)
| Title |
|---|
| 陆皝明等: "N-氰乙基-N-甲基羰基氧乙基邻氯苯胺合成", 《化工管理》 * |
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