CN108546225B - Process for producing nitrile and corresponding amine - Google Patents
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- CN108546225B CN108546225B CN201810213995.8A CN201810213995A CN108546225B CN 108546225 B CN108546225 B CN 108546225B CN 201810213995 A CN201810213995 A CN 201810213995A CN 108546225 B CN108546225 B CN 108546225B
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Abstract
The present invention relates to a process for the production of nitriles and their corresponding amines. Compared with the prior art, the method for preparing the nitrile has the characteristics of obviously reduced ammonia source consumption, small environmental pressure, low energy consumption, low production cost, high purity and yield of nitrile products and the like, and can obtain the nitrile with a more complex structure. The invention also relates to a method for producing the corresponding amine from the nitrile.
Description
The present application is a divisional application of the chinese application having the invention name "method for producing nitrile and corresponding amine" with the application number of 201410522493.5 (application date of 9/29/2014).
Technical Field
The present invention relates to a method for producing a nitrile and a method for producing a corresponding amine from the nitrile.
Background
Aromatic mononitriles have a wide range of uses and the demand of the markets at home and abroad has been increasing year by year in recent years. For example, benzonitrile is an important intermediate for synthesizing chemicals such as pesticides, aromatic amines, and the like, is an intermediate for high-grade coatings such as benzoguanamine, and is also a solvent for resin polymers, nitrile rubbers, and coatings. The o-methylbenzonitrile can be used for synthesizing agricultural bactericides such as kresoxim-methyl, mefenacet, flutolanil and the like. M-tolunitrile is an important intermediate of pesticides, medicines and dyes, and is widely applied to the production of fine chemicals. P-tolunitrile is one of the main raw materials of fluorescent whitening agents, and is widely applied to the synthesis of medicines, dyes and other fine chemical products. When the amidine compound synthesized by taking o-tolunitrile and o-ethylbenzonitrile as raw materials can be used as medicines such as epinephrine, fibrin receptor and thrombin inhibitor. The isopropylbenzonitrile can be used for synthesizing isopropylaniline, the p-isopropylaniline has wide application range, can be used for synthesizing pesticide additives (low-toxicity and high-efficiency agricultural chemical herbicide isoproturon) and medicines (such as antiviral agent intermediate 2-phenyl-3-methyl-7-aminoquinoline-4-ketone), and also has wide application in the production of coatings, dyes and other agricultural chemicals.
At present, the main method adopted for producing the aromatic mononitrile is an aromatic hydrocarbon ammoxidation method. Although the ammoxidation method has the advantages of cheap and easily available raw materials, short reaction route, easy product treatment and the like, the ammoxidation method has the following four serious problems: (1) to increase the yield, NH3The dosage is too large; (2) a large amount of waste ammonia water is generated in the reaction process, which causes great pressure on the environment and the post-treatment; (3) the reaction substrate range is narrow, and the selectivity is low when alkyl mononitriles are prepared; (4) the reaction temperature is higher (above 410 ℃), and the preparation requirement of the catalyst is high.
The carboxylic acid amination method is mainly used for producing aliphatic mononitriles, but there are few reports on a technique for producing aromatic mononitriles by the carboxylic acid amination method.
However, the inventors of the present invention have found through studies that, in the prior art, when a nitrile is produced by a carboxylic acid amination method, in order to sufficiently perform the amination reaction, ammonia gas is required to be continuously fed into the reaction system as a raw material during the entire amination process of a carboxylic acid or for a long reaction time, and therefore, the amount of ammonia gas used is large, which may be tens of millions of times the amount required for the actual amination reaction, resulting in an extremely low ammonia gas utilization rate. In addition, because the utilization rate of ammonia gas is extremely low, a large amount of waste ammonia water is generated in the ammoniation reaction but cannot be recycled, and huge pressure is caused to the environment after the ammonia gas is discharged, so that the ammonia gas is not in accordance with the current popular green environmental protection production concept. Moreover, the ammoniation reaction of the technology adopts overall higher reaction temperature (such as over 300 ℃) and overall longer reaction time, so the energy consumption is higher, the production cost is higher, and the problems of serious reaction material loss (such as reaction material is entrained out of the reaction system because of continuous ammonia gas flow) in the reaction process, more side reactions, difficult effective improvement of the quality and yield of nitrile products and the like exist. In addition, in order to obtain a high nitrile yield, the prior art also requires that ammonia gas with an extremely low water content be used as a reaction raw material, and ammonia gas continuously introduced during the whole ammoniation reaction process be used as an entrainer to discharge water as a by-product of the reaction at any time.
Accordingly, there is still a need for a process for producing an aromatic mononitrile, which is simple and suitable for industrial production, and which can overcome the above-mentioned problems of the prior art production processes.
Disclosure of Invention
In the conversion from carboxylic acid to nitrile by the carboxylic acid amination process, it is necessary to go through an intermediate step of conversion from carboxylic acid to amide and a final step of conversion from amide to nitrile. The present inventors have found that the conversion reaction in the intermediate step can be completed in a shorter reaction time and can effectively prevent side reactions if it is carried out at a lower reaction temperature than in the prior art. Furthermore, the present inventors have further found that the final step can be performed well even in the absence of ammonia. The present inventors have also found that the aforementioned problems can be solved by using a nitrile production process having the two specific steps, and thus have completed the present invention. The appearance of the new process of the two-step method with low cost and high efficiency has very important significance for breaking the monopoly abroad and developing nitrile compounds and downstream products thereof in China. The invention also relates to a method for producing amines using said nitriles.
Specifically, the present invention relates to the following aspects.
1. A method for producing a nitrile, comprising the steps of:
the first step is as follows: reacting a carboxylic acid source with an ammonia source at a reaction temperature T from T1 to T2AUnder the condition of contact for 0.01-2.5 hours to obtain an amide intermediate product, wherein the carboxylic acid source is selected from aromatic monocarboxylic acid and C of the aromatic monocarboxylic acid1-4One or more of a linear or branched alkyl ester, an anhydride of the aromatic monocarboxylic acid, and an ammonium salt of the aromatic monocarboxylic acid, T1 is the greater of the melting point and temperature of the carboxylic acid source at 1 atm for a temperature of 125 ℃, T2 is the aromatic monocarboxylic acid at 1 atmMinimum of boiling point, sublimation temperature and decomposition temperature, provided that T2>T1，
Said ammonia source being continuously supplied in gaseous form, selected from ammonia gas, said ammonia source having an ammonia content of 75-95 wt%, the remainder being an inert diluent selected from water vapour or liquid water, and said first step being carried out in an open reaction system,
or the ammonia source is ammonia gas or an ammonia generating substance, or the ammonia source is ammonia water or an ammonia generating substance aqueous solution, and the first step is carried out in a closed reaction system,
And
the second step: subjecting the amide intermediate to a reaction temperature T of from T3 to T4BUnder-heat treatment for a reaction time of 0.1 to 4.5 hours, wherein T3 is the greater of the melting point and temperature value of 200 ℃ at 1 atm of the amide intermediate product, and T4 is the minimum of the boiling point, sublimation temperature and decomposition temperature of the amide intermediate product at 1 atm, with the proviso that T4 is used>T3，
Wherein the aromatic monocarboxylic acid is selected from one or more of the compounds having the following structural formula:
R-COOH，
wherein the radical R is C6-20Aryl or C4-20A heteroaryl group; said R is optionally substituted by one or more groups selected from halogen, hydroxy, mercapto, amino, aminocarbonyl, nitro, cyano, optionally substituted C1-6Straight or branched chain (halo) alk (oxy, thio, amino, carbonyl) yl, optionally substituted C2-6Straight or branched chain (halo) ene (oxy, thio, amino, carbonyl), optionally substituted C2-6Straight or branched (halo) alkynyl (oxy, thio, amino, carbonyl) group, optionally substituted C3-20Cycloalkyl, optionally substituted C3-20Cycloalkane (oxy, thio, amino) radicals, optionally substituted C3-20Cycloalkyl radical C1-6Straight or branched chain (halo) alk (oxy, thio, amino, carbonyl) yl, optionally substituted C3-20Cycloalkyl radical C1-6Straight or branched chain (halo) ene (oxy, thio, amino, carbonyl), optionally substituted C 3-20Cycloalkyl radical C1-6Straight or branched (halo) alkynes (oxy)Sulfur, ammonia, carbonyl), optionally substituted C3-20Cycloalkenyl, optionally substituted C3-20Cycloalkene (oxy, thio, amino) radical, optionally substituted C3-20Cycloalkenyl radical C1-6Straight or branched chain (halo) alkyl (oxy, thio, amino, carbonyl) radical, optionally substituted C3-20Cycloalkenyl radical C1-6Straight or branched chain (halo) ene (oxy, thio, amino, carbonyl), optionally substituted C3-20Cycloalkenyl radical C1-6Straight or branched (halo) alkynyl (oxy, thio, amino, carbonyl) group, optionally substituted C6-20Aryl, optionally substituted C6-20Aryl (oxy, thio, amino) radicals, optionally substituted C6-20Aryl radical C1-6Straight or branched chain (halo) alk (oxy, thio, amino, carbonyl) yl, optionally substituted C6-20Aryl radical C1-6Straight or branched chain (halo) ene (oxy, thio, amino, carbonyl), optionally substituted C6-20Aryl radical C1-6Straight or branched (halo) alkynyl (oxy, thio, amino, carbonyl) group, optionally substituted C4-20Heteroaryl, optionally substituted C4-20Heteroaryl (oxy, thio, amino) radical, optionally substituted C4-20Heteroaryl C1-6Straight or branched chain (halo) alk (oxy, thio, amino, carbonyl) yl, optionally substituted C4-20Heteroaryl C1-6Straight or branched chain (halo) ene (oxy, thio, amino, carbonyl), optionally substituted C4-20Heteroaryl C1-6Straight or branched (halo) alkynyl (oxy, thio, amino, carbonyl) group, optionally substituted C 2-20Heterocyclyl, optionally substituted C2-20Heterocyclic (oxy, thio, amino) radical, optionally substituted C2-20Heterocyclyl radical C1-6Straight or branched chain (halo) alk (oxy, thio, amino, carbonyl) yl, optionally substituted C2-20Heterocyclyl radical C1-6Straight or branched chain (halo) ene (oxy, thio, amino, carbonyl) and optionally substituted C2-20Heterocyclyl radical C1-6Linear or branched (halo) alkynyl (oxy, thio, amino, carbonyl) substituents,
the expression "optionally substituted" means optionally substituted by one or more groups selected from halogen, hydroxy, mercapto, amino, aminocarbonyl, nitro, oxo, thio, cyano, C1-6Straight-chain or branched (halo) alk (oxy, thio, amino, carbonyl) yl, C2-6Straight or branched chain(halo) ene (oxy, thio, amino, carbonyl) radical, C2-6Straight-chain or branched (halo) alkyne (oxy, thio, amino, carbonyl), C3-20Cycloalkyl radical, C3-20Cycloalkyl radical C1-6Straight-chain or branched (halo) alk (oxy, thio, amino, carbonyl) yl, C3-20Cycloalkyl radical C1-6Straight-chain or branched (halo) ene (oxy, thio, amino, carbonyl) group, C3-20Cycloalkyl radical C1-6Straight-chain or branched (halo) alkyne (oxy, thio, amino, carbonyl), C3-20Cycloalkenyl radical, C3-20Cycloalkenyl radical C1-6Straight-chain or branched (halo) alk (oxy, thio, amino, carbonyl) yl, C3-20Cycloalkenyl radical C1-6Straight-chain or branched (halo) ene (oxy, thio, amino, carbonyl) group, C3-20Cycloalkenyl radical C 1-6Straight-chain or branched (halo) alkynes (oxy, thio, amino, carbonyl), C6-20Aryl radical, C6-20Aryl radical C1-6Straight-chain or branched (halo) alkyl (oxy, thio, amino, carbonyl) radical, C6-20Aryl radical C1-6Straight-chain or branched (halo) ene (oxy, thio, amino, carbonyl), C6-20Aryl radical C1-6Straight-chain or branched (halo) alkynes (oxy, thio, amino, carbonyl), C4-20Heteroaryl, C4-20Heteroaryl C1-6Straight-chain or branched (halo) alkyl (oxy, thio, amino, carbonyl) radical, C4-20Heteroaryl C1-6Straight-chain or branched (halo) ene (oxy, thio, amino, carbonyl) group, C4-20Heteroaryl C1-6Straight-chain or branched (halo) alkyne (oxy, thio, amino, carbonyl), C2-20Heterocyclic group, C2-20Heterocyclyl radical C1-6Straight-chain or branched (halo) alk (oxy, thio, amino, carbonyl) yl, C2-20Heterocyclyl radical C1-6Straight or branched chain (halo) ene (oxy, thio, amino, carbonyl) and C2-20Heterocyclyl radical C1-6Linear or branched (halo) alkynyl (oxy, thio, amino, carbonyl) substituents, where when a plurality of such substituents are present, adjacent two substituents may be bonded to each other to form a divalent substituent structure,
the expression "cycloalkane (oxy, thio, amino) group" means: cycloalkoxy, cycloalkylthio or cycloalkylamino, the expression "cycloalkene (oxy, thio, amino) group" means: cycloalkenyloxy, cycloalkenylthio or cycloalkenylamino, the expression "aryl (oxy, thio, amino) group" means: aryloxy, arylthio or arylamino, the expression "heteroaryl (oxy, thio, amino) group" means: heteroaryloxy, heteroarylthio or heteroarylamino, the expression "heterocyclic (oxy, thio, amino) group" means: a heterocyclic oxy group, a heterocyclic thio group or a heterocyclic amino group,
The expression "(halo) alk (oxy, thio, amino, carbonyl) yl" means: alkyl, haloalkyl, alkoxy, alkylthio, alkylamino, alkylcarbonyl, haloalkoxy, haloalkylthio, haloalkylamino or haloalkylcarbonyl, the expression "(halo) ene (oxy, thio, amino, carbonyl) group" has the meaning: alkenyl, haloalkenyl, alkenyloxy, alkenylthio, alkenylamino, alkenylcarbonyl, haloalkenyloxy, haloalkenylthio, haloalkenylamino or haloalkenylcarbonyl, the expression "(halo) alkyne (oxy, thio, amino, carbonyl) group" having the meaning: alkynyl, haloalkynyl, alkynyloxy, alkynylthio, alkynylamino, alkynylcarbonyl, haloalkynyloxy, haloalkynylthio, haloalkynylamino or haloalkynylcarbonyl.
2. The method for producing a nitrile of any one of the preceding aspects, wherein in the first step, the carboxylic acid source and the ammonia source are reacted at a reaction temperature T from T1 to T2AAnd the reaction time is 0.05-2 hours.
3. The method for producing a nitrile of any one of the preceding aspects, wherein in the first step, the carboxylic acid source and the ammonia source are reacted at a reaction temperature T from T1 to T2AThe reaction time of 0.3-0.8 hour.
4. The method for producing a nitrile of any one of the preceding aspects, wherein in the first step, the carboxylic acid source and the ammonia source are reacted at a reaction temperature T from T1 to T2 AFor a reaction time of 0.2 to 0.5 hours.
5. The method for producing a nitrile of any one of the preceding aspects, wherein in the second step, the amide intermediate is subjected to a reaction temperature T from T3 to T4BHeat treatment for a reaction time of 0.2 to 3 hours.
6. The method for producing a nitrile of any one of the preceding aspects, wherein in the second step, the amide intermediate is subjected to a reaction temperature T from T3 to T4BUnder heat treatment for a reaction time of 0.4 to 1 hour.
7. The method for producing a nitrile of any one of the preceding aspects, wherein in the second step, the amide intermediate is subjected to a reaction temperature T from T3 to T4BThe lower heat treatment is carried out for a reaction time of 0.3 to 0.5 hours.
8. The process for producing a nitrile as described in any of the above aspects, wherein T2-T1 ℃ is 10 ℃ or higher, and T4-T3 ℃ is 10 ℃ or higher.
9. The method for producing a nitrile according to any of the preceding aspects, wherein the reaction temperature TAFrom T1' to T2', wherein T1' ═ T1+5 ℃, or T1+10 ℃, or T1+20 ℃, or T1+30 ℃, or T1+40 ℃, or T1+50 ℃, or T1+60 ℃, or T1+70 ℃, or T1+80 ℃, or T1+90 ℃, T2' ═ T2, or T2-5 ℃, or T2-10 ℃, or T2-20 ℃, or T2-30 ℃, or T2-40 ℃, or T2-50 ℃, or 390 ℃, provided that T2' >T1'; the reaction temperature TBFrom T3 'to T4', wherein T3'═ T3+5 ℃, or T3+10 ℃, or T3+20 ℃, or T3+30 ℃, or T3+40 ℃, or T3+50 ℃, or T3+60 ℃, or T3+70 ℃, or T3+80 ℃, T4' ═ T4, or T4-5 ℃, or T4-10 ℃, or T4-20 ℃, or T4-30 ℃, or T4-40 ℃, or T4-50 ℃, or T400 ℃, provided that T4 'is'>T3'。
10. The method of making a nitrile according to any of the preceding aspects, wherein T1 is 125 ℃, or 130 ℃, or 140 ℃, or 150 ℃, or 160 ℃, or 170 ℃, or 180 ℃, or 190 ℃, or 200 ℃, or 210 ℃, or 220 ℃, or 230 ℃, or 240 ℃, or 250 ℃, or 260 ℃, or 270 ℃, or 280 ℃, or 290 ℃, or 300 ℃, or 310 ℃; t2 is 390 ℃, or 380 ℃, or 370 ℃, or 360 ℃, or 350 ℃, or 340 ℃, or 330 ℃, or 320 ℃, or 310 ℃, or 300 ℃, or 290 ℃, or 280 ℃, or 270 ℃, or 260 ℃, or 250 ℃; t3 is 200 ℃, or 210 ℃, or 220 ℃, or 230 ℃, or 240 ℃, or 250 ℃, or 300 ℃, or 310 ℃; t4 is 400 ℃, or 390 ℃, or 380 ℃, or 370 ℃, or 360 ℃, or 350 ℃, or 340 ℃, or 330 ℃, or 320 ℃, or 310 ℃, or 300 ℃, or 290 ℃, or 280 ℃, or 270 ℃, or 260 ℃, or 250 ℃.
11. The method for producing a nitrile according to any of the preceding aspects, wherein the second step is performed under reduced pressure.
12. The method for producing a nitrile according to any of the preceding aspects, wherein the first step does not use a catalyst, and the second step is performed in the presence of a catalyst or without using a catalyst.
13. The method for producing a nitrile as described in any of the preceding aspects, wherein the ammonia source is continuously supplied in gaseous form, selected from ammonia gas, and the carboxylic acid source in terms of carboxyl groups is reacted with NH3The molar ratio of the ammonia source is calculated as 1: 20, up to 1: 500; or the ammonia source is ammonia gas or an ammonia generating substance, and the carboxylic acid source is the carboxylic acid source and NH calculated by carboxyl3The molar ratio of the ammonia source is 1: 1.1-2.5; or the ammonia source is ammonia water or an aqueous solution of an ammonia-generating substance, and the carboxylic acid source in terms of carboxyl groups is reacted with NH3The molar ratio of the ammonia source is 1: 1.1-9.5.
14. The method for producing a nitrile of any of the preceding aspects, wherein the first step is carried out in a closed reaction system, and in order to contact the carboxylic acid source and the ammonia source, the ammonia source is added to the carboxylic acid source at a time in a predetermined ratio or streams of both are mixed with each other in a predetermined ratio to react.
15. The method for producing a nitrile of any of the preceding aspects, wherein the ammonia source is continuously supplied in gaseous form, selected from ammonia gas, and the ammonia content of the ammonia source is 85 to 95 wt%.
16. The method for producing a nitrile according to any of the preceding aspects, wherein the ammonia source is industrial waste ammonia gas or industrial waste aqueous ammonia.
17. The method for producing a nitrile of any of the preceding aspects, wherein the ammonia source is continuously supplied in gaseous form, the ammonia source is ammonia gas, and the carboxylic acid source in terms of carboxyl groups is reacted with NH3The molar ratio of the ammonia source is calculated to be the lowest1: 30, max 1: 300.
18. the method for producing a nitrile of any of the preceding aspects, wherein the ammonia source is continuously supplied in gaseous form, the ammonia source is ammonia gas, and the carboxylic acid source in terms of carboxyl groups is reacted with NH3The molar ratio of the ammonia source is calculated as 1: 40, up to 1: 200.
19. the method for producing a nitrile of any of the preceding aspects, wherein the ammonia source is continuously supplied in gaseous form, the ammonia source is ammonia gas, and the carboxylic acid source in terms of carboxyl groups is reacted with NH3The molar ratio of the ammonia source is calculated as 1: 50, up to 1: 80.
20. the method for producing a nitrile of any of the above aspects, wherein the ammonia source is ammonia gas or an ammonia-generating substance, and the carboxylic acid source is reacted with NH in terms of carboxyl groups 3The molar ratio of the ammonia source is 1: 1.2-2.0.
21. The method for producing a nitrile according to any of the preceding aspects, wherein the ammonia source is ammonia gas or an ammonia-generating substance, and the carboxylic acid source is a mixture of a carboxylic acid source in terms of carboxyl groups and NH3The molar ratio of the ammonia source is 1: 1.3-1.6.
22. The method for producing a nitrile according to any of the above aspects, wherein the ammonia source is aqueous ammonia or an aqueous solution of an ammonia-generating substance, and the carboxylic acid source is a mixture of the carboxylic acid source in terms of carboxyl groups and NH3The molar ratio of the ammonia source is 1: 1.3-5.6.
23. The method for producing a nitrile according to any of the above aspects, wherein the ammonia source is aqueous ammonia or an aqueous solution of an ammonia-generating substance, and the carboxylic acid source is a mixture of the carboxylic acid source in terms of carboxyl groups and NH3The molar ratio of the ammonia source is 1: 1.3-2.5.
24. The method for producing a nitrile according to any of the above aspects, wherein the ammonia source is aqueous ammonia or an aqueous solution of an ammonia-generating substance, and the carboxylic acid source is a mixture of the carboxylic acid source in terms of carboxyl groups and NH3The molar ratio of the ammonia source is 1: 1.3-1.6.
25. The method for producing a nitrile according to any of the preceding aspects, wherein the carboxylic acid source is a carboxylic acid, an anhydride or a methyl ester of the carboxylic acid shown in table 1 below; in the first step, the reaction temperature was T shown in Table 1 below AThe reaction time of the first step is 0.05 to 2 hours; when the second step is carried out in an open reaction system or under pressurized conditions, the reaction temperature is T shown in Table 1 belowBThe reaction time of the second step is 0.2 to 3 hours; when the second step is carried out under reduced pressure, the reaction temperature is T 'shown in the following Table 1-1'BThe reaction time of the second step is 0.1 to 1.5 hours,
TABLE 1
| Carboxylic acids | Reaction temperature TA，℃ | Reaction temperature TB，℃ |
| Benzoic acid | 170-245 | 200-225 |
| P-methyl benzoic acid | 180-270 | 250-270 |
| 1-naphthoic acid | 180-295 | 250-400 |
| 2-naphthoic acid | 190-295 | 250-400 |
| 4-Pyridinecarboxylic acids | 310-390 | 320-330 |
| 2-Furanecarboxylic acid | 160-230 | 250-270 |
| 3-thiophenecarboxylic acid | 170-270 | 250-310 |
| 4-nitrobenzoic acid | 245-295 | 300-325 |
| 4-aminobenzoic acid | 195-255 | 280-310 |
| 4-hydroxybenzoic acid | 225-285 | 300-325 |
| 4-methoxybenzoic acid | 200-255 | 275-315 |
| 4-chlorobenzoic acid | 255-300 | 305-325 |
| 4-Phenylbenzoic acid | 235-295 | 305-325 |
| 4-Cyanobenzoic acid | 235-285 | 300-315 |
| 9-Anthraenecarboxylic acid | 235-285 | 300-320 |
| 4- (octyloxy) benzoic acid | 125-225 | 250-300 |
| 4' -hydroxybiphenyl-4-acetic acid | 300-325 | 330-345 |
| 4-methylthiobenzoic acid | 210-275 | 300-325 |
| 3, 5-diaminobenzoic acid | 255-300 | 315-330 |
| 1-pyrenecarboxylic acid | 285-315 | 325-340 |
| 3-amino-4-methylbenzoic acid | 185-265 | 285-315 |
| 3-Pyridinylcarboxylic acids | 235-295 | 300-325 |
| Quinoline-2-carboxylic acid | 175-215 | 235-300 |
| Pyrazine-2-carboxylic acid | 235-275 | 300-325 |
| 5-bromo-3-pyridinecarboxylic acid | 195-265 | 285-315 |
| 4-methyl-3-pyridinecarboxylic acid | 185-245 | 265-300 |
| Pyrazole-3-carboxylic acid | 235-285 | 300-335 |
| Quinoxaline-2-carboxylic acid | 235-285 | 300-325 |
| 4-n-butyl-3-pyridinecarboxylic acid | 125-225 | 250-300 |
| Thiazole-4-carboxylic acid | 220-280 | 300-325 |
| 2-methyl-4-thiazolecarboxylic acid | 175-265 | 275-305 |
| 2-phenyl-1, 3-thiazole-4-carboxylic acid | 195-245 | 265-295 |
| 2-bromo-4-thiazolecarboxylic acid | 250-300 | 310-325 |
TABLE 1-1
26. The method for producing a nitrile according to any of the preceding aspects, wherein in the first step, the upper limit of the reaction temperature is TA max-5℃、TA max-10℃、TA max-15 ℃ or TA max-20 ℃ of which TA maxRefer to said TAThe upper limit value in said table 1.
27. The method for producing a nitrile of any one of the preceding aspects, wherein the reaction time of the first step is 0.1 to 1.5 hours.
28. The method for producing a nitrile of any one of the preceding aspects, wherein the reaction time of the first step is 0.2 to 0.5 hours.
29. The process for producing a nitrile in accordance with any one of the preceding aspects, wherein when the second step is carried out in an open reaction system or under pressurized conditions, the upper limit of the reaction temperature is TB max-5℃、TB max-10℃、TB max-15 ℃ or TB max-20 ℃ of which TB maxRefer to said TBUpper limit values in said table 1.
30. The method for producing a nitrile according to any of the preceding aspects, wherein when the second step is carried out in an open reaction system or under pressurized conditions, the reaction time of the second step is 0.3 to 2 hours.
31. The method for producing a nitrile according to any of the preceding aspects, wherein when the second step is carried out in an open reaction system or under pressurized conditions, the reaction time of the second step is 0.4 to 1 hour.
32. The process for producing a nitrile according to any one of the preceding aspects, wherein when the second step is carried out under reduced pressure, the upper limit of the reaction temperature is T'B max-5℃、T'B max-10℃、T'B max-15 ℃ or T'B max-20 ℃ of T'B maxIs referred to as T'BThe upper limit value in said Table 1-1.
33. The method for producing a nitrile of any of the preceding aspects, wherein when the second step is performed under reduced pressure, the reaction time of the second step is 0.2 to 0.8 hours.
34. The method for producing a nitrile of any of the preceding aspects, wherein when the second step is performed under reduced pressure, the reaction time of the second step is 0.3 to 0.5 hours.
35. The method for producing a nitrile of any one of the preceding aspects, wherein the group R is C6-12Aryl or C4-9A heteroaryl group.
36. The method for producing a nitrile of any of the preceding aspects, wherein the first step obtains an ammonia-containing effluent simultaneously with the amide intermediate product, and the ammonia-containing effluent is recycled to be supplied to the first step as a supplement to or a part of the ammonia source.
37. The method for producing a nitrile of any of the preceding aspects, wherein the effluent containing ammonia is recycled to be supplied to the first step as a supplement to or a part of the ammonia source after being concentrated or dried.
38. The method for producing a nitrile of any of the preceding aspects, wherein the carboxylic acid source is of biological origin.
39. The method for producing a nitrile according to any of the preceding aspects, wherein the carboxylic acid source is directly used as an industrially corresponding crude product.
40. The method for producing a nitrile according to any of the preceding aspects, wherein the ammonia source is an industrial waste or an industrial byproduct containing ammonia or the ammonia-producing substance.
41. The method for producing a nitrile according to any of the preceding aspects, wherein the contacting is performed in a continuous, semi-continuous or batch manner.
42. The method for producing a nitrile of any one of the preceding aspects, wherein the reaction in the closed reaction system is performed at a pressure higher than ambient pressure.
43. The method for producing a nitrile according to any of the preceding aspects, wherein the first step and the second step are performed in the same reactor or different reactors.
44. The method for producing a nitrile in any one of the preceding aspects, wherein the second step is performed in an open reaction system or a closed reaction system.
45. The method for producing a nitrile according to any of the preceding aspects, wherein no ammonia source is used in the second step.
46. The method for producing a nitrile according to any of the preceding aspects, wherein the reduced pressure condition is achieved by maintaining a degree of vacuum in the reaction system of the second step, and the degree of vacuum has a value in the range of 5 to 1000 mbar.
47. The method for producing a nitrile according to any of the preceding aspects, wherein the vacuum degree has a value in the range of 20 to 500 mbar.
48. The method for producing a nitrile according to any of the preceding aspects, wherein the vacuum degree has a value in the range of 50 to 250 mbar.
49. The method for producing a nitrile according to any of the preceding aspects, wherein the reaction temperature T of the second step is set by the reduced pressure conditionBFurther reducing 40 to 130 ℃ and further reducing the reaction time of the second step by 40-80%.
50. The method for producing a nitrile according to any of the preceding aspects, wherein the first step is performed under autogenous pressure.
51. The method for producing a nitrile of any of the preceding aspects, wherein the ammonia content of the aqueous ammonia solution is 10 to 30 wt%, and the ammonia-producing substance concentration of the ammonia-producing substance aqueous solution is 20 wt% to the saturated concentration.
52. A method for producing an amine, comprising the steps of:
the first step is as follows: producing a nitrile according to the production method described in any one of the foregoing aspects 1 to 51; and
the second step: the nitrile obtained in the first step is hydrogenated to produce an amine.
Technical effects
Compared with the prior art, the invention has the following advantages.
According to the nitrile production method of the present invention, an ammonia source (such as ammonia gas or the like) is used as a reactant only in the first step, and no ammonia source is used at all in the second step, so that the amount of the ammonia source can be significantly reduced, and the utilization rate of the ammonia source can be greatly improved.
According to the method for preparing the nitrile, the utilization rate of the ammonia source is obviously improved, so that the amount of the waste ammonia water generated by the reaction can be effectively reduced, the environmental pressure is low, and the method conforms to the current popular green environmental protection production concept.
According to the method for producing a nitrile of the present invention, there is no strict requirement for the water content of the ammonia source, and even ammonia water or vaporized ammonia water can be used as it is without using the ammonia source as an entrainer for water as a by-product. Moreover, according to the nitrile production method of the present invention, it was found for the first time in the art that waste ammonia water or waste ammonia gas (hereinafter, referred to as ammonia-containing effluent) generated by the ammoniation reaction can be directly introduced into the first step of the production method as a supplement to the ammonia source, thereby achieving 100% recycling of ammonia-containing wastewater/gas and further reducing the environmental pressure of the production method.
According to the nitrile production method of the present invention, the reaction temperature and the reaction time are significantly reduced as a whole compared to the prior art, thereby exhibiting advantages of reduced energy consumption, reduced production costs, and simple production process.
According to the method for producing a nitrile of the present invention, the reaction process is simple, side reactions are less likely to occur, and the effect of impurities on the amination reaction is less likely to occur, and therefore, the production method requires less purity of the ammonia source and the carboxylic acid source, and enables direct use of the respective crude products as the reaction raw materials. For example, the invention discovers for the first time in the field that the nitrile manufacturing method can even directly use ammonia-containing industrial waste or byproducts as ammonia sources, thereby opening up a new way for recycling or reusing various ammonia-containing industrial waste or byproducts and meeting the current green production concept.
According to the method for producing a nitrile of the present invention, the reaction conditions are simple, and the process can be smoothly carried out even without a catalyst (especially, the first step), which not only reduces the production cost of the nitrile but also reduces the complexity of subsequent separation or purification of the nitrile product.
According to the method for producing a nitrile of the present invention, the first step is carried out at a relatively low reaction temperature for a relatively short reaction time, and the second step is carried out without using any ammonia source at all, so that the loss (entrainment) of the reaction material due to the supply of the ammonia source and the like can be greatly reduced, and the present invention can achieve a nitrile yield of 75% or more, 80% or more, 90% or more, 95% or more, or even 98% or more, depending on the kind of the nitrile product.
According to the method for producing a nitrile of the present invention, the reaction conditions are mild, and side reactions are less likely to occur, whereby a nitrile product having a high purity (for example, 97% or more) can be obtained.
According to the nitrile production method of the present invention, a nitrile having a more complex structure (for example, a nitrile containing various hetero atoms, unsaturated bonds or ring structures or a (hetero) aromatic nitrile) can be produced by a carboxylic acid amination method, which has been achieved for the first time in the art, thereby greatly expanding the application range of the carboxylic acid amination method.
According to the amine production method of the present invention, since the high-purity nitrile produced according to the present invention is used as a raw material, there are advantages in that side reactions are less, the purity of the amine product is correspondingly high, and the production cost is low.
Detailed Description
Reference will now be made in detail to the present embodiments of the present invention, but it should be understood that the scope of the invention is not limited by the embodiments, but is defined by the appended claims.
All publications, patent applications, patents, and other references mentioned in this specification are herein incorporated by reference in their entirety. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification, including definitions, will control.
When the specification states a material, method, component, apparatus, or device in the "known to one skilled in the art" or the like, the term means that the specification includes those conventionally used in the art at the time of filing this application, but also includes those not currently in use, but which would become known in the art to be suitable for a similar purpose.
In addition, all ranges set forth herein are inclusive of their endpoints unless expressly stated otherwise. Further, when a range, one or more preferred ranges, or a plurality of upper preferable values and lower preferable values, are given for an amount, concentration, or other value or parameter, it is to be understood that all ranges formed from any pair of any upper range limit or preferred value and any lower range limit or preferred value are specifically disclosed, regardless of whether such pairs of values are individually disclosed.
In the context of this specification, unless explicitly defined otherwise, or the meaning is beyond the understanding of those skilled in the art, a hydrocarbon or hydrocarbon derivative group of 3 or more carbon atoms (such as propyl, propoxy, butyl, butane, butene, butenyl, hexane, etc.) has the same meaning when not preceded by the prefix "n". For example, propyl is generally understood to be n-propyl, and butyl is generally understood to be n-butyl.
In the context of the present specification, the term "ammonia source" refers to any substance that can be used as a source of ammonia gas (i.e., supply ammonia) in the nitrile production process (first step) of the present invention, including various forms of products of ammonia such as liquid ammonia, gaseous ammonia, vaporized aqueous ammonia, and the like, and also including substances that can generate ammonia gas (hereinafter referred to as ammonia-producing substances) under the reaction conditions of the first step (such as decomposition reaction by hydrolysis or thermal decomposition or the like), such as urea, cyanic acid, and ammonium salts of inorganic acids (such as ammonium carbonate and ammonium bicarbonate), and the like. The process for producing a nitrile of the present invention has a simple reaction process, less side reactions, and less influence of impurities on the amination reaction, and thus has a low requirement for the purity of an ammonia source. In view of this, in the context of the present specification, the term "ammonia source" also includes industrial waste or industrial by-products containing ammonia or containing the aforementioned ammonia-producing substances, including various industrial waste or industrial by-products in gaseous, liquid or solid form, such as ammonia-containing off-gases (such as from a synthetic ammonia process), waste ammonia gas, waste ammonia water (such as from a prior art nitrile production process), waste urea water, waste ammonium carbonate water, and the like. In general, the industrial waste or by-product can be used as it is without being subjected to a prior purification treatment as long as the kind or content of impurities other than ammonia and water in the industrial waste or by-product does not significantly affect the nitrile production process of the present invention (for example, the reduction in the nitrile yield is not more than 5%). Such impurities are generally chemically inert to the nitrile production process of the present invention, and include, for example, hydrogen, nitrogen, air, water vapor, liquid water, and the like, and may be regarded as an inert diluent for the production process. Of course, a person skilled in the art can confirm whether or not a certain industrial waste or industrial by-product contains or excessively contains impurities that significantly affect the method for producing a nitrile of the present invention by a simple test (for example, by measuring the degree of decrease in the nitrile yield), and thus confirm whether or not it can be directly applied to the method for producing a nitrile of the present invention. In addition, according to need, those skilled in the art can also reduce such impurities contained in a certain industrial waste or industrial by-product to a level that does not significantly affect the practice of the nitrile production process of the present invention by conventionally known technical means, and, according to need, concentrate the concentration of ammonia in a certain industrial waste or industrial by-product to a level more suitable for the practice of the nitrile production process of the present invention (for example, concentrate the concentration of ammonia or an ammonia-producing substance to 10 to 95 wt%, preferably 25 to 95 wt%, based on the total amount of the industrial waste or industrial by-product).
In the context of the present specification, the term "carboxylic acid source" refers to any substance that can be used as a source of carboxylic acid (i.e., to provide carboxylic acid) in the nitrile production process (first step) of the present invention, including the carboxylic acid starting material itself and a substance that is capable of producing a free carboxylic acid under the reaction conditions of the first step (such as by hydrolysis or aminolysis, etc.) (hereinafter referred to as a carboxylic acid-producing substance), such as carboxylic acid anhydride and carboxylic acid C may be mentioned1-4Linear or branched alkyl esters, and the like, and sometimes ammonium carboxylates. The process for producing a nitrile according to the present invention has a simple reaction process, less side reactions, and less influence of impurities on the amination reaction, and therefore, the purity of the carboxylic acid source required for the production process is also low (for example, the purity may be 90% at the minimum), and an industrially relevant crude product can be used as it is.
In the context of the present invention, the term "carboxylic acid" is used in its broadest definition to refer to compounds containing a free carboxyl group (i.e., -COOH).
In the context of the present specification, the term "monocarboxylic acid" refers to a compound containing only one free carboxyl group.
In the context of the present specification, the term "open reaction system" means that the reaction system is open to the outside atmosphere throughout (using an open reactor), when the reaction in the reaction system is carried out at (approximately) the pressure of the outside atmosphere (ambient pressure).
In the context of the present specification, the term "closed reaction system" means that the reaction system is isolated from the outside atmosphere throughout (using an closed reactor). According to circumstances, the reaction in the reaction system may be carried out under a pressure higher than the ambient pressure (i.e., a pressurized condition such as autogenous pressure; there is no particular limitation as long as it is a pressure range safe in production), but it is not excluded that the reaction system is opened to the outside atmosphere once or more (e.g., 1 to 20 times, 1 to 10 times, 1 to 5 times, 1 to 3 times, 1 to 2 times, or 1 time, etc.) for a short time (e.g., for 0.05 to 5 minutes, 0.1 to 4 minutes, 0.3 to 3 minutes, 0.5 to 2 minutes, or 0.6 to 1.5 minutes, etc.) throughout the whole reaction process, as long as it is opened to the outside atmosphere. Alternatively, the reaction in the reaction system may be carried out under a pressure lower than the ambient pressure (i.e., reduced pressure condition), depending on the case. The reduced pressure condition can be achieved by maintaining the reaction system at a certain vacuum degree (for example, by connecting a vacuum pump). The value of the vacuum is generally 5 to 1000mbar, preferably 20 to 500mbar or 50 to 250 mbar.
In the context of the present specification, the term "halogen" refers to fluorine, chlorine, bromine and iodine, preferably chlorine and bromine.
In the context of the present specification, the expression "optionally substituted" means optionally substituted by one or more (such as 1 to 5, 1 to 4, 1 to 3, 1 to 2 or 1) groups selected from halogen, hydroxy, mercapto, amino, aminocarbonyl, nitro, oxo, thio, cyano, C1-6Straight-chain or branched (halo) alkyl (oxy, thio, amino, carbonyl) radical, C2-6Straight-chain or branched (halo) ene (oxy, thio, amino, carbonyl), C2-6Straight-chain or branched (halo) alkynes (oxy, thio, amino, carbonyl), C3-20Cycloalkyl, C3-20Cycloalkyl radical C1-6Straight-chain or branched (halo) alkyl (oxy, thio, amino, carbonyl) radical, C3-20Cycloalkyl radical C1-6Straight-chain or branched (halo) ene (oxy, thio, amino, carbonyl), C3-20Cycloalkyl radical C1-6Straight-chain or branched (halo) alkynes (oxy, thio, amino, carbonyl), C3-20Cycloalkenyl radical, C3-20Cycloalkenyl radical C1-6Straight-chain or branched (halo) alk (oxy, thio, amino, carbonyl) yl, C3-20Cycloalkenyl radical C1-6Straight-chain or branched (halo) ene (oxy, thio, amino, carbonyl) group, C3-20Cycloalkenyl radical C1-6Straight-chain or branched (halo) alkyne (oxy, thio, amino, carbonyl), C6-20Aryl radical, C6-20Aryl radical C1-6Straight-chain or branched (halo) alk (oxy, thio, amino, carbonyl) yl, C6-20Aryl radical C1-6Straight-chain or branched (halo) ene (oxy, thio, amino, carbonyl) group, C6-20Aryl radical C1-6Straight-chain or branched (halo) alkyne (oxy, thio, amino, carbonyl), C 4-20Heteroaryl, C4-20Heteroaryl C1-6Straight-chain or branched (halo) alkyl (oxy, thio, amino, carbonyl) radical, C4-20Heteroaryl C1-6Straight-chain or branched (halo) ene (oxy, thio, amino, carbonyl), C4-20Heteroaryl C1-6Straight-chain or branched (halo) alkynes (oxy, thio, amino, carbonyl), C2-20Heterocyclic group, C2-20Heterocyclyl radical C1-6Straight-chain or branched (halo) alk (oxy, thio, amino, carbonyl) yl, C2-20Heterocyclyl radical C1-6Straight-chain or branched (halo) ene (oxy, thio, amino, carbonyl) and C2-20Heterocyclyl radical C1-6Linear or branched (halo) alkynyl (oxy, thio, amino, carbonyl) substituents. When a plurality of these substituents are present, two adjacent substituents (for example, molecular chain ends of two substituents) may be bonded to each other to form a divalent substituent structure. For example, two adjacent C1-6The linear or branched alkyl groups may be bonded to each other to form a corresponding alkylene structure. Or, two adjacent C1-6Straight-chain or branched alkoxy radicals may, for example, form the corresponding alkylenedioxy structure, adjacent two C1-6Straight-chain or branched alkylamino radicals may, for example, form the corresponding alkylenediamino structure, two adjacent C1-5Straight-chain or branched alkylthio groups, for example, may form the corresponding alkylenedisulfide structures, and the like. Preferred substituents include halogen, hydroxy, mercapto, amino, oxo or C 1-6Straight or branched chain (halo) alkyl (oxy, thio, amino, carbonyl) groups, and the like.
In the context of the present specification, the expression "(halo) alk (oxy, thio, amino, carbonyl) yl" means: alkyl, haloalkyl, alkoxy, alkylthio, alkylamino, alkylcarbonyl, haloalkoxy, haloalkylthio, haloalkylamino or haloalkylcarbonyl, the expression "(halo) ene (oxy, thio, amino, carbonyl) group" means: alkenyl, haloalkenyl, alkenyloxy, alkenylthio, alkenylamino, alkenylcarbonyl, haloalkenyloxy, haloalkenylthio, haloalkenylamino or haloalkenylcarbonyl, the expression "(halo) alkyne (oxy, thio, amino, carbonyl)" means: alkynyl, haloalkynyl, alkynyloxy, alkynylthio, alkynylamino, alkynylcarbonyl, haloalkynyloxy, haloalkynylthio, haloalkynylamino or haloalkynylcarbonyl.
In the description aboveHereinafter, the term "C3-20Cycloalkyl "refers to monocyclic, bicyclic or polycyclic cycloalkyl groups having 3 to 20 ring carbon atoms. As said C3-20Examples of the cycloalkyl group include monocyclic cycloalkyl groups such as cyclopropyl, cyclohexyl and cyclopentyl, and dicyclopentyl, decahydronaphthyl, adamantyl and spiro [2.4 ] ]Heptaalkyl, spiro [4.5 ]]Decyl, bicyclo [3.2.1 ] benzene]Octyl, tricyclo [2.2.1.0 ]2,6]Octyl, norbornyl, ethyl, propyl, butyl, isobutyl, pentyl, hexyl, octyl, and octyl,
And spirocyclic, bridged or fused ring bicyclic or polycyclic cycloalkyl groups. As said C3-20Cycloalkyl, more preferably C3-15A cycloalkyl group.
In the context of the present specification, the term "C3-20Cycloalkenyl "refers to the foregoing C3-20A group in which at least one ring carbon-carbon single bond (C-C) of the cycloalkyl group is replaced by a carbon-carbon double bond (C ═ C). As said C3-20Examples of the cycloalkenyl group include monocyclic cycloalkenyl groups such as cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl and cyclooctatetraenyl, and dicyclopentadienyl, norbornenyl, norbornadiyl, and the like,
And spirocyclic, bridged or fused cyclic bicyclic or polycyclic cycloalkenyl groups. As said C3-20Cycloalkenyl group, more preferably C3-15A cycloalkenyl group.
In the context of the present specification, the term "C6-20Aryl "refers to an aromatic hydrocarbon group having 6 to 20 ring carbon atoms. As said C6-20Examples of the aryl group include a group in which two or more benzene rings are directly connected by a single bond, such as a phenyl group, a biphenyl group, and a terphenyl group, and a group in which two or more benzene rings are condensed, such as a naphthyl group, an anthryl group, and a phenanthryl group. As said C 6-20Aryl groups, more preferably phenyl and biphenyl.
In the context of the present specification, the term "C4-20Heteroaryl "refers to a group having 4-20 ring carbonsAnd aromatic hydrocarbon groups of 1 to 3 ring heteroatoms selected from oxygen, sulfur and nitrogen. As said C4-20Examples of the heteroaryl group include furyl, thienyl, pyrrolyl, thiazolyl, benzothiazolyl, thiadiazolyl, imidazolyl, benzimidazolyl, triazinyl, triazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, quinolyl, pteridinyl, and acridinyl groups, and among them, furyl, thienyl, imidazolyl, pyridyl, and indolyl groups are preferable.
In the context of the present specification, the term "C2-20Heterocyclyl "refers to C as previously described3-20Cycloalkyl or C3-20A group in which at least one of the ring carbon atoms of the cycloalkenyl group is replaced with an oxygen atom, a sulfur atom, or a nitrogen atom. As said C2-20Examples of the heterocyclic group include a piperidyl group, a piperazinyl group, an azacyclohexenyl group, a dioxolanyl group, a dioxanyl group, a tetrahydrofuryl group, an oxetanyl group, an azepinyl group, a pyrrolinyl group, a tetrahydropyridinyl group, a tetrahydropyrazolyl group, a pyrazolinyl group, a pyranyl group, a thiopyranyl group, a tetrahydropyrrolyl group, a tetrahydrothienyl group, an aziridinyl group, a tetrahydropyranyl group, a tetrahydrothiopyranyl group and a morpholinyl group, and among them, a piperidyl group, a tetrahydrofuryl group, a tetrahydropyranyl group and the like are preferable.
In the context of the present specification, the term "ammonia-containing effluent" refers to a gaseous or liquid material containing ammonia (such as ammonia-containing condensed water, ammonia-containing waste water, ammonia-containing off-gas, and the like) discharged as a by-product or unreacted raw material from the reaction system during and/or after the reaction in the process for producing a nitrile of the present invention (particularly, the first step).
Finally, unless otherwise explicitly indicated, all percentages, parts, ratios, etc. referred to in this specification are by weight unless not otherwise generally recognized by those of skill in the art.
The present invention relates to a method for producing a nitrile, which is characterized by comprising a first step and a second step described below.
According to this first step of the invention, the carboxylic acid source is reacted with the ammonia source at a reaction temperature T from T1 to T2ALower jointFor a reaction time of from 0.01 to 2.5 hours, wherein T1 is the greater of the melting point and temperature value of the carboxylic acid source at 1 atm and 125 ℃, and T2 is the minimum of the boiling point, sublimation temperature and decomposition temperature of the aromatic monocarboxylic acid at 1 atm, with the proviso that T2 is used >T1. Preferably, T2-T1 is 10 ℃ or higher.
According to the invention, the carboxylic acid source is selected from the group consisting of aromatic monocarboxylic acids, C of said aromatic monocarboxylic acids1-4Linear or branched alkyl esters (preferably methyl esters), anhydrides of the aromatic monocarboxylic acids or ammonium salts of the aromatic monocarboxylic acids. These carboxylic acid sources may be used singly or in combination of two or more.
According to the present invention, the aromatic monocarboxylic acid may be a compound having the following structure.
R-COOH，
Wherein the radical R is C6-20(preferably C)6-12) Aryl or C4-20(preferably C)4-9) A heteroaryl group.
According to the invention, said R may be optionally substituted by one or more (such as 1 to 4, 1 to 3, 1 to 2 or 1) groups selected from halogen, hydroxy, mercapto, amino, aminocarbonyl, nitro, cyano, optionally substituted C1-6Straight or branched chain (halo) alk (oxy, thio, amino, carbonyl) yl, optionally substituted C2-6Straight or branched chain (halo) ene (oxy, thio, amino, carbonyl), optionally substituted C2-6Straight or branched (halo) alkynyl (oxy, thio, amino, carbonyl) group, optionally substituted C3-20Cycloalkyl, optionally substituted C3-20Cycloalkane (oxy, thio, amino) radicals, optionally substituted C3-20Cycloalkyl radical C1-6Straight or branched chain (halo) alk (oxy, thio, amino, carbonyl) yl, optionally substituted C 3-20Cycloalkyl radical C1-6Straight or branched (halo) ene (oxy, thio, amino, carbonyl), optionally substituted C3-20Cycloalkyl radical C1-6Straight or branched (halo) alkyne (oxy, thio, amino, carbonyl), optionally substituted C3-20Cycloalkenyl, optionally substituted C3-20Cycloalkene (oxy, thio, amino) radical, optionally substituted C3-20Cycloalkenyl radicalsC1-6Straight or branched chain (halo) alkyl (oxy, thio, amino, carbonyl) radical, optionally substituted C3-20Cycloalkenyl radical C1-6Straight or branched chain (halo) ene (oxy, thio, amino, carbonyl), optionally substituted C3-20Cycloalkenyl radical C1-6Straight or branched (halo) alkynyl (oxy, thio, amino, carbonyl) group, optionally substituted C6-20Aryl, optionally substituted C6-20Aryl (oxy, thio, amino) radicals, optionally substituted C6-20Aryl radical C1-6Straight or branched chain (halo) alk (oxy, thio, amino, carbonyl) yl, optionally substituted C6-20Aryl radical C1-6Straight or branched chain (halo) ene (oxy, thio, amino, carbonyl), optionally substituted C6-20Aryl radical C1-6Straight or branched (halo) alkynyl (oxy, thio, amino, carbonyl) group, optionally substituted C4-20Heteroaryl, optionally substituted C4-20Heteroaryl (oxy, thio, amino) radical, optionally substituted C4-20Heteroaryl C1-6Straight or branched chain (halo) alk (oxy, thio, amino, carbonyl) yl, optionally substituted C4-20Heteroaryl C1-6Straight or branched chain (halo) ene (oxy, thio, amino, carbonyl), optionally substituted C 4-20Heteroaryl C1-6Straight or branched (halo) alkyne (oxy, thio, amino, carbonyl), optionally substituted C2-20Heterocyclyl, optionally substituted C2-20Heterocyclic (oxy, thio, amino) radicals, optionally substituted C2-20Heterocyclyl radical C1-6Straight or branched chain (halo) alkyl (oxy, thio, amino, carbonyl) radical, optionally substituted C2-20Heterocyclyl radical C1-6Straight or branched (halo) ene (oxy, thio, amino, carbonyl) and optionally substituted C2-20Heterocyclyl radical C1-6The substituents of the straight or branched (halo) alkyne (oxy, thio, amino, carbonyl) group are substituted at the available positions.
Here, the expression "cycloalkane (oxy, thio, amino) group" means: cycloalkoxy, cycloalkylthio or cycloalkylamino, the expression "cycloalkene (oxy, thio, amino) group" means: cycloalkenyloxy, cycloalkenylthio or cycloalkenylamino, the expression "aryl (oxy, thio, amino) group" means: aryloxy, arylthio or arylamino, the expression "heteroaryl (oxy, thio, amino) group" means: heteroaryloxy, heteroarylthio or heteroarylamino, the expression "heterocyclic (oxy, thio, amino) group" means: heterocyclic oxy, heterocyclic thio or heterocyclic amino.
Examples of the possible substitution positions include any positions that can be substituted (substituted for the corresponding hydrogen atom) on the group R, such as a meta position or a para position of-COOH on the group R.
According to the present invention, as the carboxylic acid source, the aforementioned aromatic monocarboxylic acids may be used singly or in combination of two or more.
According to the present invention, the carboxylic acid source may be of biological origin, for example, natural aromatic carboxylic acids or mixed aromatic carboxylic acids as industrial (e.g., oil and fat industry) by-products, etc., as long as they contain impurities or impurity levels that reduce the yield of the target nitrile by not more than 5%.
According to the invention, the carboxylic acid source is at the reaction temperature TAIt is preferable that the liquid is in a molten state or a liquid state. In view of this, the aromatic monocarboxylic acid, C of the aromatic monocarboxylic acid1-4The linear or branched alkyl ester or the anhydride of the aromatic monocarboxylic acid preferably has the reaction temperature T equal to or less thanA(typically up to 390 ℃ C.) melting point (measured at 1 atm). The melting point of these carboxylic acid sources at 1 atm (and the boiling point, sublimation temperature, decomposition temperature, etc. of the aromatic monocarboxylic acid at 1 atm) can be known to those skilled in the art by referring to the relevant technical manuals or by conventional measurement methods, and thus, will not be described herein in detail.
According to an embodiment of the present invention, the carboxylic acid source and the ammonia source are contacted with each other, for example, by continuously supplying (for example, feeding) the ammonia source in a gaseous form to the (preferably previously melted) carboxylic acid source.
According to this embodiment of the invention, the ammonia source is as described above, with ammonia gas or vaporized ammonia water being preferred, in particular industrial waste ammonia gas or vaporized industrial waste ammonia water. In this case, the ammonia source may have an ammonia content of, for example, 20 to 99.9 wt%, 25 to 99.9 wt%, 40 to 99.9 wt%, 60 to 99.9 wt%, 75 to 99.9 wt%, 85 to 99.9 wt%, or 95 to 99.9 wt%, with the remainder being the inert diluent or the like as described above.
According to this embodiment of the invention, the ammonia source is supplied (fed) continuously throughout the first step. The amount of the ammonia source to be used (as a whole) in this case is not particularly limited as long as the nitrile yield predetermined in the present invention can be achieved. For example, the carboxylic acid source in terms of carboxyl groups and NH according to the actual reaction conditions3The molar ratio of the ammonia source may be at least 1: 20. 1: 30. 1: 40 or 1: 50, etc., up to no excessive waste of the ammonia source, such as may be 1: 500. 1: 400. 1: 300. 1: 200. 1: 100 or 1: 80, etc., but may not be limited thereto.
According to this embodiment of the invention, the first step is typically carried out in an open reaction system (such as an open reaction kettle). The ammonia source is continuously supplied to the reaction system (containing the molten carboxylic acid source) while the ammonia-containing effluent is continuously withdrawn from the reaction system.
According to another embodiment of the present invention, the carboxylic acid source and the ammonia source may be contacted with each other by, for example, adding the ammonia source to the (preferably previously melted) carboxylic acid source at a time in a predetermined ratio or mixing the streams of the two with each other in a predetermined ratio to react. In general, the contact may be carried out continuously, semi-continuously, or intermittently, and is not particularly limited.
According to this embodiment of the invention, the ammonia source is as described hereinbefore, with ammonia gas or an ammonia generating substance being preferred, and industrial waste ammonia gas being more preferred. In this case, the ammonia content of the ammonia source may be, for example, 60 to 99.9 wt%, 80 to 99.9 wt%, 85 to 99.9 wt%, or 95 to 99.9 wt%, with the remainder being the inert diluent or the like as described above. In this case, the amount of the carboxylic acid source is such that the amount of the carboxylic acid source in terms of carboxyl groups is equal to the amount of NH3The molar ratio of the ammonia source is up to 1: 1.1-2.5, preferably 1: 1.2-2.0, more preferably 1: 1.3-1.6.
According to this embodiment of the present invention, as the ammonia source, ammonia water or an ammonia-producing substance may also be usedAmong the aqueous solutions, aqueous ammonia is preferred, and industrial waste aqueous ammonia is more preferred. Wherein the ammonia content of the aqueous ammonia is generally 10 to 30% by weight, preferably 25 to 28% by weight. In this case, the amount of the carboxylic acid source to be used as the ammonia source is such that the amount of the carboxylic acid source to be used is equal to the amount of NH in terms of carboxyl groups3The molar ratio of the ammonia source is up to 1: 1.1-9.5, preferably 1: 1.2-7.0, more preferably 1: 1.3-5.6, 1: 1.3-2.5, 1: 1.3-2.0 or 1: 1.3-1.6.
According to this embodiment of the present invention, the ammonia generating substance is a substance that can be decomposed under the reaction conditions of the first step to generate ammonia gas. As the ammonia generating substance, one or more selected from urea, cyanic acid, ammonium carbonate, ammonium bicarbonate and ammonium chloride are preferable, one or more selected from urea and ammonium bicarbonate are preferable, and ammonium bicarbonate is more preferable.
According to this embodiment of the present invention, the ammonia generator concentration of the ammonia generator aqueous solution may be, for example, 20 wt% to a saturated concentration (preferably a saturated concentration) or the like, but is not limited thereto. As the aqueous solution of the ammonia-producing substance, an industrial waste or an industrial by-product containing the ammonia-producing substance, such as waste urea water and waste ammonium carbonate water, is more preferable.
According to this embodiment of the invention, the first step is typically carried out in a closed reaction system (e.g., a closed reaction vessel). If desired, this first step can be carried out in a completely closed reaction system, i.e. the reaction system does not need to be open in any way to the outside atmosphere during the entire reaction. In view of this, the closed reaction system generally exhibits pressurized conditions (such as the autogenous pressure of the first step).
According to this embodiment of the present invention, an ammonia-containing effluent is also discharged as a by-product to the outside of the reaction system in a continuous, semi-continuous or batch manner, simultaneously with the formation of the amide intermediate product.
It is preferred according to the present invention that the ammonia-containing effluent obtained in any of the preceding embodiments, preferably after concentration or drying, is recycled to be supplied to the first step as a supplement or part of the ammonia source. This can correspondingly reduce the amount of fresh ammonia source supplied to the first step, thereby increasing the utilization of ammonia raw material and achieving effective recycling of ammonia-containing effluent (such as ammonia-containing wastewater and ammonia-containing tail gas).
The inventors of the present invention have found that the first step can be performed well even without using any catalyst that is generally used in the art for performing a carboxylic acid amination process. Thus, according to a preferred embodiment of the invention, no catalyst is used in the first step.
According to the invention, although not essential, the first step may be carried out in the presence of a solvent to promote melting of the carboxylic acid source. Examples of the solvent include any solvent which can dissolve the carboxylic acid source without adversely affecting the conversion reaction in the first step, and more specifically, examples thereof include an aromatic hydrocarbon solvent such as toluene or xylene, a strongly polar solvent such as DMF or DMSO, an organic basic solvent such as 2-picoline, a halogenated hydrocarbon solvent such as methylene chloride, and water. The amount of the solvent is, for example, generally 20 to 50% by weight based on the weight of the carboxylic acid source, but it is not limited to this.
According to the invention, the reaction time of the first step is preferably 0.05 to 2 hours, alternatively 0.1 to 1.5 hours, alternatively 0.2 to 1 hour, alternatively 0.3 to 0.8 hour, alternatively 0.2 to 0.5 hour or less.
According to the present invention, immediately after the end of the first step, the supply of the ammonia source is stopped, or the ammonia source is removed from the reaction system of the first step.
According to the invention, after the end of the first step, the amide intermediate obtained can be used as a starting material for the second step, or can be subjected to the second step after temporary storage or the like. Alternatively, although not necessarily, the obtained amide intermediate may be washed with dilute ammonia or the like to remove a possibly remaining unreacted carboxylic acid source.
According to the present invention, the first step and the second step may be performed in the same reactor or in different reactors, and are not particularly limited. When the reaction is carried out in the same reactor, the amide intermediate product is not discharged after the first step, and the reaction conditions in the first step are directly changed to those in the second step (described below), thereby reducing the production cost and production complexity of the production process. When carried out in different reactors, these reactors may be connected in series, with the latter reactor being fed by the discharge of the former reactor, thereby allowing a succession of said first step and said second step, either continuously, semi-continuously or batchwise.
According to the present invention, examples of the reactor in the first step or the second step include a reaction vessel, a fixed bed reactor, a fluidized bed reactor, and the like. These reactors may be used alone or in combination of two or more kinds, and are not particularly limited.
According to the second step, the amide intermediate obtained in the first step is subjected to a reaction temperature T ranging from T3 to T4 BUnder-heat treatment for a reaction time of 0.1 to 4.5 hours, wherein T3 is the greater of the melting point and temperature value of 200 ℃ at 1 atm of the amide intermediate product, and T4 is the minimum of the boiling point, sublimation temperature and decomposition temperature of the amide intermediate product at 1 atm, with the proviso that T4 is used>T3. Preferably, T4-T3 is 10 ℃ or higher.
According to the invention, the amide intermediate is reacted at the reaction temperature TBThe lower layer preferably assumes a molten state or a liquid state. In view of this, the amide intermediate preferably has the reaction temperature T equal to or less thanB(typically up to 400 ℃) in the presence of a suitable solvent. The melting point, boiling point, sublimation temperature, decomposition temperature, etc. of these amide intermediates at 1 atm can be known to those skilled in the art by referring to the relevant technical manual or by the conventional measurement method, and therefore, the details thereof are not described herein.
According to the present invention, although not essential, the second step may be carried out in the presence of a solvent. Examples of the solvent include any solvent which can dissolve the amide intermediate without adversely affecting the conversion reaction in the second step, and more specifically, examples thereof include aromatic hydrocarbon solvents such as toluene and xylene, strongly polar solvents such as DMF and DMSO, and organic basic solvents such as 2-picoline. The solvent is used, for example, in an amount of usually 20 to 50% by weight based on the weight of the amide intermediate, but it is not limited thereto in some cases.
According to the present invention, the reaction time of the second step is preferably 0.2 to 3 hours, alternatively 0.3 to 2 hours, alternatively 0.4 to 1.2 hours, alternatively 0.4 to 1 hour, alternatively 0.3 to 0.5 hours or less.
According to the invention, no ammonia source (such as any ammonia source described hereinbefore) is used in the second step, such as (completely) stopping the supply of the ammonia source. In other words, the second step is carried out in the absence of the ammonia source.
According to the invention, the second step may be carried out in the presence of a catalyst or without a catalyst. Examples of the catalyst include those conventionally used in the art for the carboxylic acid amination method, and more specifically, examples thereof include phosphorus pentoxide, phosphorus oxychloride, thionyl chloride, phosphoric acid, phosphorus pentachloride, Bugess reagent, and TFAA-NEt3Reagent, (COCl)2-NEt3-DMSO reagent, methanesulfonyl chloride or titanium tetrachloride, etc., among which phosphorus pentoxide is preferred. When used, these catalysts may be used in amounts customary in the art (for example, from 0.1 to 10%, preferably from 0.2 to 5%, by weight based on the weight of the amide intermediate), without particular limitation.
According to a further embodiment of the invention, the reaction temperature TAFrom T1 'to T2'. At this time, the T1' is T1+5 ℃, or T1+10 ℃, or T1+20 ℃, or T1+30 ℃, or T1+40 ℃, or T1+50 ℃, or T1+60 ℃, or T1+70 ℃, or T1+80 ℃, or T1+90 ℃. T2' is T2, or T2-5 ℃, or T2-10 ℃, or T2-20 ℃, or T2-30 ℃, or T2-40 ℃, or T2-50 ℃, but typically up to 390 ℃. Provided that is T2'>T1'. Preferably, T2 '-T1'. gtoreq.10 ℃.
According to a further embodiment of the invention, the reaction temperature TBFrom T3 'to T4'. In this case, T3' is T3+5 ℃, or T3+10 ℃, or T3+20 ℃, or T3+30 ℃, or T3+40 ℃, or T3+50 ℃, or T3+60 ℃, or T3+70 ℃, or T3+80 ℃. T4' is T4, or T4-5 ℃, or T4-10 ℃, or T4-20 ℃, or T4-30 ℃, or T4-40 ℃, or T4-50 ℃, but typically up to 400 ℃. With the proviso that T4'>T3'. Preferably, T4 '-T3'. gtoreq.10 ℃.
According to a further embodiment of the present invention, said T1 is 125 ℃, or 130 ℃, or 140 ℃, or 150 ℃, or 160 ℃, or 170 ℃, or 180 ℃, or 190 ℃, or 200 ℃, or 210 ℃, or 220 ℃, or 230 ℃, or 240 ℃, or 250 ℃, or 260 ℃, or 270 ℃, or 280 ℃, or 290 ℃, or 300 ℃, or 310 ℃. According to a further embodiment of the present invention, said T2 is 390 ℃, or 380 ℃, or 370 ℃, or 360 ℃, or 350 ℃, or 340 ℃, or 330 ℃, or 320 ℃, or 310 ℃, or 300 ℃, or 290 ℃, or 280 ℃, or 270 ℃, or 260 ℃, or 250 ℃. Provided that T2> T1. Preferably, T2-T1 is 10 ℃ or higher.
According to a further embodiment of the present invention, the T3 is 200 ℃, or 210 ℃, or 220 ℃, or 230 ℃, or 240 ℃, or 250 ℃, or 300 ℃, or 310 ℃. According to a further embodiment of the present invention, the T4 is 400 ℃, or 390 ℃, or 380 ℃, or 370 ℃, or 360 ℃, or 350 ℃, or 340 ℃, or 330 ℃, or 320 ℃, or 310 ℃, or 300 ℃, or 290 ℃, or 280 ℃, or 270 ℃, or 260 ℃, or 250 ℃. Provided that T4> T3. Preferably, T4-T3 is 10 ℃ or higher.
According to the present invention, the second step may be performed in an open reaction system or a closed reaction system. When the second step is carried out in a closed reaction system, the reaction system may be under pressurized or depressurized conditions. Among them, the reduced pressure condition is preferable from the viewpoint of effectively lowering the reaction temperature. The reduced pressure condition may be obtained by allowing the reaction to proceedThe system is maintained at a certain vacuum degree (for example, by connecting a vacuum pump). At this time, the specific value of the degree of vacuum depends on whether or not the objective nitrile product can be efficiently separated from the reaction system by distillation at the (predetermined) reaction temperature of the second step, and thus cannot be specified in general. The skilled person can select a suitable value for the vacuum degree for this purpose by consulting the relevant technical manual or can confirm it by simple tests without technical difficulties. Nevertheless, the value range of the vacuum is generally 5 to 1000mbar, preferably 20 to 500mbar or 50 to 250 mbar. At this time, as the conversion reaction of the second step proceeds, the nitrile product formed is continuously distilled out of the reaction system of the second step together with by-product water, thereby facilitating the shift of the reaction equilibrium toward the product. By using this way of continuous distillation to remove the product in the second step, the reaction temperature of this step can be significantly reduced and the reaction time of this step can be significantly shortened. Side reactions occur less frequently in this second step due to the reduction in reaction temperature and the reduction in reaction time, thereby contributing to an increase in the yield of the nitrile product. By employing this particular reaction regime, the reaction temperature of the second step can generally be at each reaction temperature T as defined in the context of the present specification B(particularly the upper limit value thereof) of 40 to 130 ℃, preferably 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125 or 130 ℃ and the like. In addition, the reaction time of the second step can be further reduced by generally 40 to 80%, preferably 50 to 70%.
According to a preferred embodiment of the present invention, the carboxylic acid source is a carboxylic acid, an anhydride or a methyl ester of the carboxylic acid shown in table 1 below, wherein the carboxylic acid is preferred.
According to a preferred embodiment of the present invention, in said first step, the reaction temperature is generally T as indicated in Table 1 belowAThe upper limit of the reaction temperature is more preferably TA max-5℃、TA max-10℃、TA max-15 ℃ or TA max-20℃Wherein T isA maxRefer to said TAThe upper limit values in table 1 below. In the first step, the reaction time is typically from 0.05 to 2 hours, alternatively from 0.1 to 1.5 hours, alternatively from 0.2 to 1 hour, alternatively from 0.3 to 0.8 hour, alternatively from 0.2 to 0.5 hour.
According to a preferred embodiment of the present invention, when the second step is carried out in an open reaction system or under pressurized conditions as described above, the reaction temperature is generally T shown in Table 1 belowBThe upper limit of the reaction temperature is more preferably T B max-5℃、TB max-10℃、TB max-15 ℃ or TB max-20 ℃ of which TB maxRefer to said TBThe upper limit values in table 1 below. At this time, in the second step, the reaction time is generally 0.2 to 3 hours, alternatively 0.3 to 2 hours, alternatively 0.4 to 1.2 hours, alternatively 0.4 to 1 hour.
TABLE 1
| Carboxylic acids | Reaction temperature TA，℃ | Reaction temperature TB，℃ |
| Benzoic acid | 170-245 | 200-225 |
| Para methyl benzoic acid | 180-270 | 250-270 |
| 1-naphthoic acid | 180-295 | 250-400 |
| 2-naphthoic acid | 190-295 | 250-400 |
| 4-Pyridinecarboxylic acids | 310-390 | 320-330 |
| 2-Furanecarboxylic acid | 160-230 | 250-270 |
| 3-thiophenecarboxylic acid | 170-270 | 250-310 |
| 4-nitrobenzoic acid | 245-295 | 300-325 |
| 4-aminobenzoic acid | 195-255 | 280-310 |
| 4-hydroxybenzoic acid | 225-285 | 300-325 |
| 4-methoxybenzoic acid | 200-255 | 275-315 |
| 4-chlorobenzoic acid | 255-300 | 305-325 |
| 4-Phenylbenzoic acid | 235-295 | 305-325 |
| 4-nitrilobenzoic acid | 235-285 | 300-315 |
| 9-Anthraenecarboxylic acid | 235-285 | 300-320 |
| 4- (octyloxy) benzoic acid | 125-225 | 250-300 |
| 4' -hydroxybiphenyl-4-acetic acid | 300-325 | 330-345 |
| 4-methylthiobenzoic acid | 210-275 | 300-325 |
| 3, 5-diaminobenzoic acid | 255-300 | 315-330 |
| 1-pyrenecarboxylic acid | 285-315 | 325-340 |
| 3-amino-4-methylbenzoic acid | 185-265 | 285-315 |
| 3-Pyridinylcarboxylic acids | 235-295 | 300-325 |
| Quinoline-2-carboxylic acid | 175-215 | 235-300 |
| Pyrazine-2-carboxylic acid | 235-275 | 300-325 |
| 5-bromo-3-pyridinecarboxylic acid | 195-265 | 285-315 |
| 4-methyl-3-pyridinecarboxylic acid | 185-245 | 265-300 |
| Pyrazole-3-carboxylic acid | 235-285 | 300-335 |
| Quinoxaline-2-carboxylic acid | 235-285 | 300-325 |
| 4-n-butyl-3-pyridinecarboxylic acid | 125-225 | 250-300 |
| Thiazole-4-carboxylic acid | 220-280 | 300-325 |
| 2-methyl-4-thiazolecarboxylic acid | 175-265 | 275-305 |
| 2-phenyl-1, 3-thiazole-4-carboxylic acid | 195-245 | 265-295 |
| 2-bromo-4-thiazolecarboxylic acid | 250-300 | 310-325 |
According to a preferred embodiment of the present invention, when the second step is carried out under reduced pressure as described above, the reaction temperature is generally T 'as shown in tables 1 to 1 below' BThe upper limit of the reaction temperature is more preferably T'B max-5℃、T′B max-10℃、T′B max-15 ℃ or T'B max-20 ℃ of T'B maxIs referred to as T'BThe upper limit values in the following Table 1-1. At this time, in the second step, the reaction time is generally 0.1 to 1.5 hours, alternatively 0.1 to 1.2 hours, alternatively 0.2 to 0.8 hours, alternatively 0.2 to 0.6 hours, alternatively 0.3 to 0.5 hours.
TABLE 1-1
According to the present invention, after the second step is completed, the objective nitrile can be separated as a product from the reaction mixture obtained in the second step by a conventional purification or separation method. Examples of the purification or separation method include a distillation method and an extraction method.
According to the present invention, the distillation or extraction method may be carried out in a manner conventional in the art, and is not particularly limited as long as the objective nitrile product can be separated from the reaction mixture.
According to the present invention, as the distillation method, for example, a vacuum distillation method using a rectifying column under the following operating conditions: the vacuum is 40-100mbar and the bottom temperature is generally 100-320 ℃ with the boiling point of the target nitrile product at said vacuum (+ -2 ℃) as cut point, generally for example 80-250 ℃, but is not limited thereto and depends on the particular target nitrile product. The reflux ratio of the rectifying column may be set to 1.1 to 3 times the minimum reflux ratio Rmin as required, and the actual number of plates is, for example, 5 to 200, but is not limited thereto and depends on the specific target nitrile product. In addition, the actual operating conditions of the rectification column are not limited thereto, and those skilled in the art can select appropriate rectification operating conditions according to the distillation properties of the objective nitrile product (such as boiling point and thermal decomposition temperature, etc.), the rectification column structure (such as the number of trays, etc.), and the actual requirements (such as a predetermined nitrile purity, etc.), etc., which are conventionally known.
According to the present invention, the extraction method includes, for example, a method of directly extracting the reaction mixture (after diluting or adjusting the reaction mixture by adding an appropriate amount of a 2 to 5 wt% dilute aqueous alkali solution as necessary) with a good solvent for the target nitrile product such as ethyl acetate, chloroform, hexane, and the like.
According to the invention, extraction and distillation can be combined, for example, by first carrying out a preliminary purification or separation by extraction and then carrying out a further purification or separation by distillation.
According to the present invention, the objective nitrile product having a purity of 97% or more (preferably 98% or more, more preferably 99% or more) can be obtained by the purification or isolation. The nitrile purity in this case can be measured conveniently by gas chromatography or the like.
According to the method for producing a nitrile of the present invention, a nitrile yield of 75% or more, 80% or more, 90% or more, 95% or more, or even 98% or more can be achieved depending on the kind of the nitrile product.
According to the present invention, the reaction temperature in the first step is significantly reduced and the reaction time is significantly shortened as compared with the prior art carboxylic acid amination method. Without being bound by any theory, the reason for this may be as follows. The prior art processes for the amination of carboxylic acids generally employ relatively high temperatures and relatively long reaction times, so that the conversion of the carboxylic acid into the amide takes place simultaneously with the conversion of the amide (which results from the previous conversion) into the nitrile. Moreover, due to the high reaction temperature, the reaction equilibrium of these two conversion reactions rapidly moves toward the respective products and also toward the respective reactants (reversion reaction), thereby producing a large amount of highly reactive intermediate compounds in the reaction system. These highly reactive intermediate compounds, by themselves or with each other or with the reactants, are very chemically reactive, and, at the same time, undergo the aforementioned conversion or reversion reactions, various undesired side reactions also occur. Moreover, these side reactions become more severe and cross-occur as the reaction time increases. In order to suppress these side reactions, the prior art carboxylic acid amination process has to use a large number of ammonia sources. However, even in this case, since the reaction temperature is high and the reaction time is long, the generation of a large amount of by-products is unavoidable, thereby making it difficult to improve the yield and quality (e.g., high product purity) of the nitrile product by the prior art carboxylic acid amination method. In response to the problem of the prior art, the present inventors have found through diligent studies that the conversion reaction from carboxylic acid to amide can be achieved only at a significantly reduced reaction temperature compared to the prior art. Moreover, the conversion reaction requires only a short reaction time to complete. Because the reaction temperature is lower, the reaction time is shorter, and side reactions rarely occur. In addition, due to the lower reaction temperature, the conversion reaction from amide to nitrile is significantly inhibited, as evidenced by the fact that almost no nitrile is detectable in the amide intermediate product obtained in the first step. At the same time, the various side reactions associated therewith are also significantly suppressed, as evidenced by the high product yield (generally above 90%) and product purity (generally above 95%) of the amide intermediate obtained in the first step, thus laying a good foundation for the continuation of the second step. Meanwhile, since the conversion reaction of the first step is substantially quantitatively performed and side reactions are rarely generated even without the inhibitory effect of the ammonia source, the ammonia utilization rate of the first step of the present invention is very high, resulting in that the ammonia consumption amount thereof can be significantly reduced as compared with the prior art.
According to the present invention, due to the presence of the first step, the second step can be well performed even without using a catalyst, or even while maintaining normal pressure, or even without actively taking measures (such as the aforementioned reduced pressure conditions) to separate the nitrile product from the reaction system, and finally the nitrile product can be obtained in a higher product yield and a higher product purity. This was the first phenomenon discovered in the art. Although the mechanism thereof is not clear, the present inventors consider that one of the reasons may be that the first step is completed in a short reaction time at a low reaction temperature to produce some other reactive intermediate other than the amide intermediate, which exhibits a catalytic effect on the conversion reaction of the second step to be followed, thereby effectively promoting the production of the objective nitrile product. Furthermore, the present inventors confirmed through specific experiments that the reactive intermediate was not a carboxylic acid source used as a reactant or a carboxylic acid freshly produced by a reverse conversion reaction.
According to the present invention, the nitriles produced as described above can be used as starting materials for the production of the corresponding amines. To this end, the invention also relates to a process for the preparation of amines by hydrogenation of the nitriles to give the corresponding amines.
According to the invention, the hydrogenation can be carried out in any manner conventionally known in the art for the hydrogenation of nitriles. For example, the nitrile feedstock may be hydrogenated in the presence of a hydrogenation catalyst for 0.2 to 3 hours (preferably 0.5 to 2 hours) at a total reaction pressure of 0.6 to 5.2MPa, a hydrogen partial pressure of 0.4 to 5MPa (e.g., 2 to 4MPa), and a reaction temperature of 70 to 130 ℃ (e.g., 80 to 120 ℃), although it is sometimes not limited thereto.
According to the present invention, as the hydrogenation catalyst, various catalysts conventionally used in the art for producing amine by nitrile hydrogenation can be directly used, such as raney nickel, iron or copper doped raney nickel, Ni-B or Ni-Co-B amorphous alloy, supported Ni-B or Ni-Co-B amorphous alloy, carrier supported noble metal (such as Pb/C, Pd/C or Rh/C, etc.) or composite catalyst (such as raney nickel/cobalt octacarbonyl), etc., wherein raney nickel is preferred from the viewpoint of easy industrial implementation, such as raney nickel sold by aladin reagent company under the specification of 50 μm or 150 μm. These hydrogenation catalysts may be used alone or in combination of two or more.
According to the invention, the hydrogenation catalyst may be used in an amount of, for example, 2 to 10 wt% (e.g., 2 to 6 wt%) on a weight basis of the nitrile starting material, but is sometimes not limited thereto.
According to the present invention, the hydrogenation reaction is preferably carried out in the presence of a solvent (otherwise known as a diluent), as is known in the art. Examples of the solvent include water; alcohols such as methanol, ethanol and 2-propanol; esters such as methyl acetate; aromatic hydrocarbons such as benzene, toluene, and xylene; cycloalkanes such as cyclohexane; alkanes such as heptane; petroleum ether, diethyl ether, dioxane, tetrahydrofuran, and the like, or any combination of these solvents, and among them, ethanol or a mixed solvent of ethanol and water (the volume ratio of ethanol to water is, for example, 0.1:1 to 1:0.1, but not limited thereto) and the like are preferable. These solvents may be used alone or in combination of two or more.
According to the present invention, the solvent may be used in an amount effective to improve the exothermic reaction without imposing an excessive burden on the subsequent product separation step, and may be, for example, 1 to 10 times, such as 1 to 5 times, 1 to 4 times, 1 to 3 times, 1 to 2 times, or the like, based on the volume of the nitrile raw material, but is not limited thereto in some cases.
According to the invention, the hydrogenation reaction can also be carried out in the presence of a hydrogenation promoter, if desired. Examples of the hydrogenation assistant include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide. These hydrogenation assistants may be used alone or in combination of two or more.
According to the invention, the hydrogenation assistant may be used in an amount of, for example, 0.3 to 2 wt% (preferably 0.2 to 1.2 wt%) on a weight basis of the nitrile raw material, but is not limited thereto in some cases.
According to the present invention, the target amine can be separated from the reaction mixture as a product by a conventional purification or separation method after the hydrogenation reaction is completed. Such purification or isolation methods are known in the art and will not be described in detail herein.
According to the method for producing an amine of the present invention, an amine yield of 85% or more, 90% or more, 95% or more, or even 98% or more can be achieved depending on the kind of the nitrile raw material, and the purity of the amine product can be 97% or more (preferably 98% or more, more preferably 99% or more).
Examples
The present invention will be described in further detail with reference to examples, but the present invention is not limited to these examples.
Preparation of amide intermediate example A
500g of carboxylic acid raw material (chemical purity) is added into a 1L open reaction kettle, stirring is started (600r/min), and ammonia gas (chemical purity, the water content is 5.1 wt%, and the flow is 100g/min) is continuously introduced into the carboxylic acid raw material from the bottom of the reaction kettle. The reaction is carried out at a reaction temperature TADown to carry out T CAfter hours, the introduction of ammonia was stopped. The contents of the reactor were sampled and subjected to nuclear magnetic hydrogen spectroscopy and elemental analysis to characterize the amide intermediate. The specific reaction conditions and the results of characterization are shown in the following tables A-1, A-2, A-3, A-4, A-5 and A-6. These characterization results indicate that the obtained amide intermediate has very high purity (above 99%).
In this example, the ammonia gas can be directly replaced by spent ammonia gas (from a winnowing petrochemical plant, containing about 50 wt% ammonia, the remainder being toluene, oxygen, nitrogen, water vapour, carbon monoxide and carbon dioxide, the spent ammonia gas having a flow rate of 130 g/min).
TABLE A-1
TABLE A-2
TABLE A-3
TABLE A-4
TABLE A-5
TABLE A-6
Nitrile product preparation example A
Example a was prepared following the amide intermediate. The reaction vessel was closed (when the boiling point of the amide intermediate at atmospheric pressure was equal to or lower than the reaction temperature T described belowBWhile the reaction vessel is kept open (when the boiling point of the amide intermediate at normal pressure is higher than the reaction temperature T described below)BAt this time), stirring was continued (600r/min) to change the reaction temperature to TBAt the reaction temperature TBLower holding TDAfter hours, the reaction was substantially complete. Then, the reaction vessel was closed and connected to a vacuum pump to make the degree of vacuum in the reaction vessel 20 to 50mbar (adjusted depending on the kind of the nitrile product), and the distillate was used as the nitrile product. The yield of the nitrile product was calculated and sampled for nuclear magnetic hydrogen spectroscopy and elemental analysis to characterize the nitrile product obtained. The specific reaction conditions and characterization results are shown in the following tables A-7, A-8, A-9, A-10 and A-11. These characterization results indicate that the nitrile product obtained is of very high purity (above 99%).
In these nitrile product production examples, 10g of phosphorus pentoxide as a catalyst was added in one portion to the reaction tank, optionally at the start of the reaction.
TABLE A-7
TABLE A-8
TABLE A-9
TABLE A-10
TABLE A-11
Nitrile product preparation example A1
Example a was prepared next to the amide intermediate. The reaction kettle is closed, the stirring is opened (600r/min), and the reaction temperature is changed into TB. Will be describedThe reactor was connected to a vacuum pump and the vacuum in the reactor was gradually reduced starting from 500mbar until a trace amount (up to about 0.5 wt%) of the amide intermediate was detected in the effluent. Maintaining the vacuum degree and the reaction time TDAfter hours, the reaction was substantially complete. The distillate was taken as the nitrile product. The yield of the nitrile product was calculated and sampled for nuclear magnetic hydrogen spectroscopy and elemental analysis to characterize the nitrile product obtained. The specific reaction conditions and characterization results are shown in the following tables A1-7, A1-8, A1-9, A1-10 and A1-11. These characterization results indicate that the obtained nitrile product has a high purity (above 92%).
In these nitrile product production examples, 10g of phosphorus pentoxide as a catalyst was added in one portion to the reaction vessel, optionally at the stage of initiation of the reaction.
TABLE A1-7
TABLE A1-8
TABLE A1-9
TABLE A1-10
TABLE A1-11
Preparation of amide intermediate example B
A1L reactor was charged with 500g of a carboxylic acid feed (Chemicals)Pure) and charged with NH3Ammonia gas (containing 0.5 wt% of water and being an industrial product) in a molar amount 1.3 times that of the carboxyl group contained in the carboxylic acid raw material was added to the reaction vessel, and the reaction vessel was closed and stirred (600 r/min). The reaction is carried out at a reaction temperature TADown to carry out TCAfter hours, the contents of the autoclave were sampled for nuclear magnetic hydrogen spectroscopy and elemental analysis to characterize the amide intermediate. The specific reaction conditions and the results of characterization are shown in the following tables B-1, B-2, B-3, B-4, B-5 and B-6. These characterization results indicate that the obtained amide intermediate has very high purity (above 99%).
In this example, the ammonia gas can be directly replaced by spent ammonia gas (from the winnowing chemical plant, containing about 50 wt% ammonia, the remainder being toluene, oxygen, nitrogen, water vapor, carbon monoxide and carbon dioxide) or ammonium bicarbonate powder (chemically pure) having a molar number of ammonium ions of 1.4 times the number of carboxyl groups contained in the carboxylic acid feedstock.
TABLE B-1
TABLE B-2
TABLE B-3
TABLE B-4
TABLE B-5
TABLE B-6
Nitrile product preparation example B
Example B was prepared following the amide intermediate. The reaction vessel was closed (when the boiling point of the amide intermediate at atmospheric pressure was equal to or lower than the reaction temperature T described below BWhile) or by keeping the reaction vessel open (when the boiling point of the amide intermediate under normal pressure is higher than the reaction temperature T described below)BAt this time), stirring was continued (600r/min) to change the reaction temperature to TBAt the reaction temperature TBLower holding TDAfter hours, the reaction was substantially complete. Then, the reaction vessel was closed and connected to a vacuum pump to make the degree of vacuum in the reaction vessel 20 to 50mbar (adjusted depending on the kind of the nitrile product), and the distillate was used as the nitrile product. The yield of the nitrile product was calculated and sampled for nuclear magnetic hydrogen spectroscopy and elemental analysis to characterize the nitrile product obtained. The specific reaction conditions and the results of characterization are shown in the following tables B-7, B-8, B-9, B-10 and B-11. These characterization results indicate that the nitrile product obtained is of very high purity (above 99%).
In these nitrile product production examples, 10g of phosphorus pentoxide as a catalyst was added in one portion to the reaction vessel, optionally at the stage of initiation of the reaction.
TABLE B-7
TABLE B-8
TABLE B-9
TABLE B-10
TABLE B-11
Nitrile product preparation example B1
Example B was prepared following the amide intermediate. The reaction kettle is closed, the stirring is opened (600r/min), and the reaction temperature is changed into TB. The reactor was connected to a vacuum pump and the vacuum in the reactor was gradually reduced starting at 500mbar until a trace amount (up to about 0.5 wt%) of the amide intermediate was detected in the bleed. Maintaining the vacuum degree and the reaction time T DAfter hours, the reaction was substantially complete. The distillate was taken as the nitrile product. The yield of the nitrile product was calculated and a sample taken for nuclear magnetic hydrogen spectroscopy and elemental analysis to characterize the nitrile product obtained. The specific reaction conditions and the characterization results are shown in the following tables B1-7, B1-8, B1-9, B1-10 and B1-11. These characterization results indicate that the nitrile product obtained has a higher purity (above 92%).
In these nitrile product production examples, 10g of phosphorus pentoxide as a catalyst was added in one portion to the reaction tank, optionally at the start of the reaction.
TABLE B1-7
TABLE B1-8
TABLE B1-9
TABLE B1-10
TABLE B1-11
Preparation of amide intermediate example C
500g of carboxylic acid starting material (chemically pure) and NH were charged in a 1L reactor3Ammonia water (NH) having a molar number 1.4 times that of the carboxyl group contained in the carboxylic acid raw material3Content 25 wt%, industrial product), the reaction kettle is closed, and the stirring is opened (600 r/min). The reaction is carried out at a reaction temperature TALower run TCAfter hours, the contents of the autoclave were sampled for nuclear magnetic hydrogen spectroscopy and elemental analysis to characterize the amide intermediate. The specific reaction conditions and the results of characterization are shown in the following tables C-1, C-2, C-3, C-4, C-5 and C-6. These characterization results indicate that the obtained amide intermediate has very high purity (above 99%).
In this example, the aqueous ammonia can be directly replaced with spent aqueous ammonia (from a petrochemical plant for a starter, containing about 20 wt% ammonia, the remainder being phenol, water, urea, sodium sulfate and carbon dioxide) or an aqueous solution of ammonium bicarbonate having 1.6 times the molar number of ammonium ions as much as the carboxyl groups contained in the carboxylic acid starting material (30 wt% ammonium bicarbonate concentration).
TABLE C-1
TABLE C-2
TABLE C-3
TABLE C-4
TABLE C-5
TABLE C-6
Nitrile product preparation example C
Example C was prepared following the amide intermediate. The reaction vessel was closed (when the boiling point of the amide intermediate at atmospheric pressure was equal to or lower than the reaction temperature T described belowBWhile the reaction vessel is kept open (when the boiling point of the amide intermediate at normal pressure is higher than the reaction temperature T described below)BAt this time), stirring was continued (600r/min) to change the reaction temperature to TBAt the reaction temperature TBLower holding TDAfter hours, the reaction was substantially complete. Then, the reaction vessel was closed and connected to a vacuum pump to make the degree of vacuum in the reaction vessel 20 to 50mbar (adjusted depending on the kind of the nitrile product), and the distillate was used as the nitrile product. The yield of the nitrile product was calculated and sampled for nuclear magnetic hydrogen spectroscopy and elemental analysis to characterize the nitrile product obtained. The specific reaction conditions and characterization results are shown in the following tables C-7, C-8, C-9, C-10 and C-11. These characterization results indicate that the nitrile product obtained is of very high purity (above 99%).
In these nitrile product production examples, 10g of phosphorus pentoxide as a catalyst was added in one portion to the reaction tank, optionally at the start of the reaction.
TABLE C-7
TABLE C-8
TABLE C-9
TABLE C-10
TABLE C-11
Nitrile product preparation example C1
Example C was prepared next to the amide intermediate. The reaction kettle is closed, the stirring is opened (600r/min), and the reaction temperature is changed into TB. The reactor was connected to a vacuum pump and the vacuum in the reactor was gradually reduced starting at 500mbar until a trace amount (up to about 0.5 wt%) of the amide intermediate was detected in the bleed. Maintaining the vacuum degree and the reaction time TDAfter hours, the reaction was substantially complete. The distillate was taken as the nitrile product. The yield of the nitrile product was calculated and sampled for nuclear magnetic hydrogen spectroscopy and elemental analysis to characterize the nitrile product obtained. The specific reaction conditions and characterization results are shown in the following tables C1-7, C1-8, C1-9, C1-10 and C1-11. These characterization results indicate that the obtained nitrile product has a high purity (above 92%).
In these nitrile product production examples, 10g of phosphorus pentoxide as a catalyst was added in one portion to the reaction vessel, optionally at the stage of initiation of the reaction.
TABLE C1-7
TABLE C1-8
TABLE C1-9
TABLE C1-10
TABLE C1-11
Amine preparation examples
(1) 100g of benzonitrile and 3g of Raney-Ni, 400mL of ethanol were added to a 1L hydrogenation vessel, and H2 was continuously charged so that the system pressure was always maintained at 7MPa during the reaction. After the reaction is carried out for 0.5h at the reaction temperature of 100 ℃, the temperature is reduced. When the temperature in the reaction kettle is reduced to room temperature, gas is discharged, and the benzylamine (with the purity of more than 99%) is obtained through filtration and recrystallization, wherein the yield is 92 wt%.
1H NMR (300MHz, DMSO). delta.7.41-7.12 (m,5H),4.05(s,2H),1.93(s,2H), elemental analysis C, 78.14; h, 8.05; and N, 13.13.
(2) 100g of p-tolunitrile and 3g of Raney-Ni, 400mL of ethanol were added to a 1L hydrogenation vessel, and H was continuously charged2The system pressure was always maintained at 8MPa during the reaction. After reacting for 0.5h at the reaction temperature of 105 ℃, cooling. To be reactedWhen the temperature in the kettle is reduced to room temperature, the gas is discharged, and p-toluidine (with the purity of more than 99 percent) is obtained through filtration and recrystallization, and the yield is 93 weight percent.
1H NMR (300MHz, DMSO) δ 7.18(d, J ═ 7.5Hz,2H),7.11(d, J ═ 7.5Hz,2H),4.04(s,2H),2.26(s,3H),1.94(s,2H), elemental analysis: C, 79.17; h, 9.08; n, 11.43.
(3) 100g of 4-pyridinecarbonitrile and 3g of Raney-Ni, 400mL of ethanol were added to a 1L hydrogenation vessel, and H was continuously charged 2The system pressure was maintained at 8MPa during the reaction. After reacting at a reaction temperature of 105 ℃ for 1h, the temperature is reduced. When the temperature in the reaction kettle is reduced to room temperature, the gas is discharged, and 4-pyridine methylamine (with the purity of more than 99 percent) is obtained through filtration and recrystallization, wherein the yield is 89wt percent.
1H NMR (300MHz, DMSO). delta.8.46 (s,1H),8.44(s,1H),7.32(s,1H),7.30(s,1H),4.78(s,2H),1.94(s,2H), elemental analysis C, 66.27; h, 7.08; n, 25.53.
(4) 100g of 4-methoxybenzonitrile, 3g of Raney-Ni and 400mL of ethanol are added into a 1L hydrogenation kettle, and H is continuously charged2The system pressure was maintained at 8MPa during the reaction. After reacting for 1h at a reaction temperature of 110 ℃, the temperature is reduced. When the temperature in the reaction kettle is reduced to room temperature, gas is discharged, and the 4-methoxybenzylamine (with the purity of more than 99 percent) is obtained through filtration and recrystallization, wherein the yield is 92 weight percent.
1H NMR (300MHz, DMSO). delta.7.12 (s,1H),7.10(s,1H),6.88(s,1H),6.86(s,1H),4.04(s,2H),3.84(s,3H),1.94(s,2H), elemental analysis C, 69.84; h, 8.16; and N, 10.08.
(5) 100g of 4-cyanobenzonitrile and 3g of Raney-Ni, 400mL of ethanol were added into a 1L hydrogenation kettle, and H was continuously charged2The system pressure was always maintained at 8MPa during the reaction. After reacting for 1h at the reaction temperature of 110 ℃, cooling. When the temperature in the reaction kettle is reduced to room temperature, gas is discharged, and the 4-cyanobenzylamine (with the purity of more than 99 percent) is obtained through filtration and recrystallization, wherein the yield is 94 percent by weight.
1H NMR (300MHz, DMSO). delta.7.74 (s,1H),7.72(s,1H),7.47(s,1H),7.44(s,1H),4.05(s,2H),1.95(s,2H), elemental analysis C, 72.43; h, 6.01; n, 21.08.
Nitrile product preparation comparative example A
400g of p-toluamide (analytically pure) is added into a 1L open reaction kettle, and stirring is started (600r/min) to ensure that the reaction temperature is TBAt 250 ℃ at the reaction temperature TBLower holding TDAfter 1 hour, the reaction vessel was closed and a vacuum pump was connected in the same manner as in nitrile product production example a, and the distillate was taken as a nitrile product. The p-tolunitrile product yield was 45% and the purity was 92% by calculation and analysis.
Nitrile product preparation comparative example B
400g of p-toluamide (analytically pure) and 100g of p-toluic acid (analytically pure) are added into a 1L open reaction kettle, and stirring is started (600r/min) to ensure that the reaction temperature is TBAt 250 ℃ at the reaction temperature TBLower holding TDAfter 1 hour, the reaction vessel was closed and a vacuum pump was connected in the same manner as in nitrile product production example a, and the distillate was taken as a nitrile product. The p-tolunitrile product was calculated and analyzed to have a yield of 55% and a purity of 95%.
Although the embodiments of the present invention have been described in detail with reference to the examples, it should be noted that the scope of the present invention is not limited by the embodiments, but is defined by the appended claims. Those skilled in the art can appropriately modify the embodiments without departing from the technical spirit and scope of the present invention, and the modified embodiments are also clearly included in the scope of the present invention.
Claims (46)
1. A method for producing a nitrile, comprising the steps of:
the first step is as follows: reacting a carboxylic acid source with an ammonia source at a reaction temperature T from T1 to T2AUnder the condition of contact for 0.01-2.5 hours to obtain an amide intermediate product, wherein the carboxylic acid source is selected from aromatic monocarboxylic acid and C of the aromatic monocarboxylic acid1-4One or more of linear or branched alkyl ester, acid anhydride of the aromatic monocarboxylic acid and ammonium salt of the aromatic monocarboxylic acidMore, T1 is the greater of the melting point and temperature value at 1 atm of the carboxylic acid source of 125 ℃, T2 is the minimum of the boiling point, sublimation temperature and decomposition temperature at 1 atm of the aromatic monocarboxylic acid, provided that T2>T1，
Said ammonia source being continuously supplied in gaseous form, selected from ammonia gas, said ammonia source having an ammonia content of 75-95wt%, the remainder being an inert diluent selected from water vapour or liquid water, and said first step being carried out in an open reaction system,
or the ammonia source is ammonia gas or an ammonia generating substance, or the ammonia source is ammonia water or an ammonia generating substance aqueous solution, and the first step is carried out in a closed reaction system,
And
the second step: subjecting the amide intermediate to a reaction temperature T of from T3 to T4BUnder-heat treatment for a reaction time of 0.1 to 4.5 hours, wherein T3 is the greater of the melting point and temperature value of 200 ℃ at 1 atm of the amide intermediate product, and T4 is the minimum of the boiling point, sublimation temperature and decomposition temperature of the amide intermediate product at 1 atm, with the proviso that T4 is used>T3，
After the end of the second step, separating the nitrile product from the reaction mixture obtained in the second step by purification or isolation,
wherein the aromatic monocarboxylic acid is selected from one or more of the compounds having the following structural formula:
R-COOH，
wherein the radical R is C6-20Aryl or C4-20A heteroaryl group; said R is optionally substituted by one or more groups selected from halogen, hydroxy, mercapto, amino, aminocarbonyl, nitro, cyano, optionally substituted C1-6Straight or branched chain (halo) alkyl (oxy, thio, amino, carbonyl) radical, optionally substituted C2-6Straight or branched chain (halo) ene (oxy, thio, amino, carbonyl), optionally substituted C2-6Straight or branched (halo) alkynyl (oxy, thio, amino, carbonyl) group, optionally substituted C3-20Cycloalkyl, optionally substituted C3-20Cycloalkanes (oxygen, sulfur, or sulfur, or sulfur or a compound, Amino), optionally substituted C3-20Cycloalkyl radical C1-6Straight or branched chain (halo) alkyl (oxy, thio, amino, carbonyl) radical, optionally substituted C3-20Cycloalkyl radical C1-6Straight or branched (halo) ene (oxy, thio, amino, carbonyl), optionally substituted C3-20Cycloalkyl radical C1-6Straight or branched (halo) alkyne (oxy, thio, amino, carbonyl), optionally substituted C3-20Cycloalkenyl, optionally substituted C3-20Cycloalkene (oxy, thio, amino) radical, optionally substituted C3-20Cycloalkenyl radical C1-6Straight or branched chain (halo) alkyl (oxy, thio, amino, carbonyl) radical, optionally substituted C3-20Cycloalkenyl radical C1-6Straight or branched chain (halo) ene (oxy, thio, amino, carbonyl), optionally substituted C3-20Cycloalkenyl radical C1-6Straight or branched (halo) alkynyl (oxy, thio, amino, carbonyl) group, optionally substituted C6-20Aryl, optionally substituted C6-20Aryl (oxy, thio, amino) radicals, optionally substituted C6-20Aryl radical C1-6Straight or branched chain (halo) alk (oxy, thio, amino, carbonyl) yl, optionally substituted C6-20Aryl radical C1-6Straight or branched chain (halo) ene (oxy, thio, amino, carbonyl), optionally substituted C6-20Aryl radical C1-6Straight or branched (halo) alkynyl (oxy, thio, amino, carbonyl) group, optionally substituted C4-20Heteroaryl, optionally substituted C4-20Heteroaryl (oxy, thio, amino) radical, optionally substituted C 4-20Heteroaryl C1-6Straight or branched chain (halo) alk (oxy, thio, amino, carbonyl) yl, optionally substituted C4-20Heteroaryl C1-6Straight or branched chain (halo) ene (oxy, thio, amino, carbonyl), optionally substituted C4-20Heteroaryl C1-6Straight or branched (halo) alkynyl (oxy, thio, amino, carbonyl) group, optionally substituted C2-20Heterocyclyl, optionally substituted C2-20Heterocyclic (oxy, thio, amino) radical, optionally substituted C2-20Heterocyclyl radical C1-6Straight or branched chain (halo) alk (oxy, thio, amino, carbonyl) yl, optionally substituted C2-20Heterocyclyl radical C1-6Straight or branched chain (halo) alkenes (oxygens)Sulfur, ammonia, carbonyl) group and optionally substituted C2-20Heterocyclyl radical C1-6Linear or branched (halo) alkynyl (oxy, thio, amino, carbonyl) substituents,
the expression "optionally substituted" means optionally substituted by one or more groups selected from halogen, hydroxy, mercapto, amino, aminocarbonyl, nitro, oxo, thio, cyano, C1-6Straight-chain or branched (halo) alk (oxy, thio, amino, carbonyl) yl, C2-6Straight-chain or branched (halo) ene (oxy, thio, amino, carbonyl) group, C2-6Straight-chain or branched (halo) alkyne (oxy, thio, amino, carbonyl), C3-20Cycloalkyl radical, C3-20Cycloalkyl radical C1-6Straight-chain or branched (halo) alk (oxy, thio, amino, carbonyl) yl, C 3-20Cycloalkyl radical C1-6Straight-chain or branched (halo) ene (oxy, thio, amino, carbonyl), C3-20Cycloalkyl radical C1-6Straight-chain or branched (halo) alkynes (oxy, thio, amino, carbonyl), C3-20Cycloalkenyl radical, C3-20Cycloalkenyl radical C1-6Straight-chain or branched (halo) alkyl (oxy, thio, amino, carbonyl) radical, C3-20Cycloalkenyl radical C1-6Straight-chain or branched (halo) ene (oxy, thio, amino, carbonyl), C3-20Cycloalkenyl radical C1-6Straight-chain or branched (halo) alkyne (oxy, thio, amino, carbonyl), C6-20Aryl radical, C6-20Aryl radical C1-6Straight-chain or branched (halo) alk (oxy, thio, amino, carbonyl) yl, C6-20Aryl radical C1-6Straight-chain or branched (halo) ene (oxy, thio, amino, carbonyl) group, C6-20Aryl radical C1-6Straight-chain or branched (halo) alkyne (oxy, thio, amino, carbonyl), C4-20Heteroaryl group, C4-20Heteroaryl C1-6Straight-chain or branched (halo) alk (oxy, thio, amino, carbonyl) yl, C4-20Heteroaryl C1-6Straight-chain or branched (halo) ene (oxy, thio, amino, carbonyl) group, C4-20Heteroaryl C1-6Straight-chain or branched (halo) alkyne (oxy, thio, amino, carbonyl), C2-20Heterocyclic group, C2-20Heterocyclyl radical C1-6Straight-chain or branched (halo) alk (oxy, thio, amino, carbonyl) yl、C2-20Heterocyclyl radical C1-6Straight or branched chain (halo) ene (oxy, thio, amino, carbonyl) and C 2-20Heterocyclyl radical C1-6Linear or branched (halo) alkynyl (oxy, thio, amino, carbonyl) substituents, where when a plurality of such substituents are present, adjacent two substituents may be bonded to each other to form a divalent substituent structure,
the expression "cycloalkane (oxy, thio, amino) group" means: cycloalkoxy, cycloalkylthio or cycloalkylamino, the expression "cycloalkene (oxy, thio, amino) group" means: cycloalkenyloxy, cycloalkenylthio or cycloalkenylamino, the expression "aryl (oxy, thio, amino) group" means: aryloxy, arylthio or arylamino, the expression "heteroaryl (oxy, thio, amino) group" having the meaning: heteroaryloxy, heteroarylthio or heteroarylamino, the expression "heterocyclic (oxy, thio, amino) group" means: a heterocyclic oxy group, a heterocyclic thio group or a heterocyclic amino group,
the expression "(halo) alk (oxy, thio, amino, carbonyl) yl" means: alkyl, haloalkyl, alkoxy, alkylthio, alkylamino, alkylcarbonyl, haloalkoxy, haloalkylthio, haloalkylamino or haloalkylcarbonyl, the expression "(halo) ene (oxy, thio, amino, carbonyl) group" means: alkenyl, haloalkenyl, alkenyloxy, alkenylthio, alkenylamino, alkenylcarbonyl, haloalkenyloxy, haloalkenylthio, haloalkenylamino or haloalkenylcarbonyl, the expression "(halo) alkyne (oxy, thio, amino, carbonyl)" means: alkynyl, haloalkynyl, alkynyloxy, alkynylthio, alkynylamino, alkynylcarbonyl, haloalkynyloxy, haloalkynylthio, haloalkynylamino or haloalkynylcarbonyl.
2. The process for producing a nitrile as claimed in claim 1, wherein T2-T1 ℃ C. is 10 ℃ or higher, and T4-T3 ℃ C. is 10 ℃ or higher.
3. The method for producing a nitrile as claimed in claim 1, wherein the reaction temperature TAIs from T1' to T2', wherein T1' = T1+5 ℃, or T1+10 ℃, or T1+20 ℃, or T1+30 ℃, or T1+40 ℃, orT1+50 ℃, or T1+60 ℃, or T1+70 ℃, or T1+80 ℃, or T1+90 ℃, T2'= T2, or T2-5 ℃, or T2-10 ℃, or T2-20 ℃, or T2-30 ℃, or T2-40 ℃, or T2-50 ℃, or 390 ℃, provided that T2'>T1'; the reaction temperature TBFrom T3 'to T4', wherein T3'= T3+5 ℃, or T3+10 ℃, or T3+20 ℃, or T3+30 ℃, or T3+40 ℃, or T3+50 ℃, or T3+60 ℃, or T3+70 ℃, or T3+80 ℃, T4' = T4, or T4-5 ℃, or T4-10 ℃, or T4-20 ℃, or T4-30 ℃, or T4-40 ℃, or T4-50 ℃, or 400 ℃, provided that T4 'is'>T3'。
4. The process for the production of a nitrile as claimed in claim 1, wherein T1 is 125 ℃, or 130 ℃, or 140 ℃, or 150 ℃, or 160 ℃, or 170 ℃, or 180 ℃, or 190 ℃, or 200 ℃, or 210 ℃, or 220 ℃, or 230 ℃, or 240 ℃, or 250 ℃, or 260 ℃, or 270 ℃, or 280 ℃, or 290 ℃, or 300 ℃, or 310 ℃; t2 is 390 ℃, or 380 ℃, or 370 ℃, or 360 ℃, or 350 ℃, or 340 ℃, or 330 ℃, or 320 ℃, or 310 ℃, or 300 ℃, or 290 ℃, or 280 ℃, or 270 ℃, or 260 ℃, or 250 ℃; t3 is 200 ℃, alternatively 210 ℃, alternatively 220 ℃, alternatively 230 ℃, alternatively 240 ℃, alternatively 250 ℃, alternatively 300 ℃, alternatively 310 ℃; t4 is 400 ℃, or 390 ℃, or 380 ℃, or 370 ℃, or 360 ℃, or 350 ℃, or 340 ℃, or 330 ℃, or 320 ℃, or 310 ℃, or 300 ℃, or 290 ℃, or 280 ℃, or 270 ℃, or 260 ℃, or 250 ℃.
5. The method for producing a nitrile as defined in claim 1, wherein the second step is performed under reduced pressure.
6. The method for producing a nitrile as defined in claim 1, wherein said first step does not use a catalyst, and said second step is performed in the presence of a catalyst or does not use a catalyst.
7. The method for producing a nitrile as defined in claim 1, wherein said ammonia source is continuously supplied in gaseous form, selected from the group consisting of ammonia gas, and said carboxylic acid source in terms of carboxyl groups and NH3The molar ratio of the ammonia source is calculated as 1: 20, up to 1: 500; or the ammonia source is ammonia gas or an ammonia generating substance, and the carboxylic acid source is the carboxylic acid source and NH calculated by carboxyl3The molar ratio of the ammonia source is 1: 1.1-2.5; or the ammonia source is ammonia water or an ammonia-generating substance aqueous solution, and the carboxylic acid source in terms of carboxyl groups is reacted with NH3The molar ratio of the ammonia source calculated is 1: 1.1-9.5.
8. The method for producing a nitrile as defined in claim 1, wherein said first step is carried out in a closed reaction system, and in order to contact said carboxylic acid source with said ammonia source, said ammonia source is added to said carboxylic acid source at a time in a predetermined ratio or streams thereof are mixed with each other in a predetermined ratio to effect a reaction.
9. The method for producing a nitrile as defined in claim 1, wherein the ammonia source is continuously supplied in a gaseous form, selected from ammonia gas, and the ammonia content of the ammonia source is 85 to 95 wt%.
10. The method for producing a nitrile as defined in claim 1, wherein the ammonia source is industrial waste ammonia gas or industrial waste aqueous ammonia.
11. The method for producing a nitrile as defined in claim 7, wherein said ammonia source is continuously supplied in gaseous form, said ammonia source is ammonia gas, and said carboxylic acid source in terms of carboxyl groups is reacted with NH3The molar ratio of the ammonia source is calculated as 1: 30, max 1: 300.
12. the method for producing a nitrile as defined in claim 7, wherein said ammonia source is continuously supplied in gaseous form, said ammonia source is ammonia gas, and said carboxylic acid source in terms of carboxyl groups is reacted with NH3The molar ratio of the ammonia source is calculated as 1: 40, up to 1: 200.
13. the method for producing a nitrile as claimed in claim 7, wherein the ammonia source is continuously supplied in a gaseous form, the ammonia source is ammonia gas, and the carboxylic acid source in terms of carboxyl groups is mixed with NH3The molar ratio of the ammonia source is calculated as 1: 50, up to 1: 80.
14. the method for producing a nitrile as claimed in claim 7, wherein the ammonia source is ammonia gas or an ammonia-generating substance, and the carboxylic acid source is reacted with NH in terms of carboxyl group 3The molar ratio of the ammonia source is 1: 1.2-2.0.
15. The method for producing a nitrile as defined in claim 7, wherein the ammonia source is ammonia gas or an ammonia generating substance, and the carboxylic acid source is a mixture of a carboxylic acid source in terms of carboxyl groups and NH3The molar ratio of the ammonia source is 1: 1.3-1.6.
16. The method for producing a nitrile as defined in claim 7, wherein the ammonia source is aqueous ammonia or an aqueous solution of an ammonia generating substance, and the carboxylic acid source is a mixture of a carboxylic acid source in terms of carboxyl groups and NH3The molar ratio of the ammonia source is 1: 1.3-5.6.
17. The method for producing a nitrile as defined in claim 7, wherein the ammonia source is aqueous ammonia or an aqueous solution of an ammonia generating substance, and the carboxylic acid source is a mixture of a carboxylic acid source in terms of carboxyl groups and NH3The molar ratio of the ammonia source is 1: 1.3-2.5.
18. The method for producing a nitrile as defined in claim 7, wherein the ammonia source is aqueous ammonia or an aqueous solution of an ammonia generating substance, and the carboxylic acid source is a mixture of a carboxylic acid source in terms of carboxyl groups and NH3The molar ratio of the ammonia source is 1: 1.3-1.6.
19. The method for producing a nitrile according to claim 1, wherein the carboxylic acid source is a carboxylic acid, an anhydride or a methyl ester of the carboxylic acid shown in Table 1 below; in the first step, the reaction temperature was T shown in Table 1 belowAReaction of the first stepThe time is 0.05-2 hours; when the second step is carried out in an open reaction system or under pressurized conditions, the reaction temperature is T shown in Table 1 below BThe reaction time of the second step is 0.2 to 3 hours; when the second step is carried out under reduced pressure, the reaction temperature is T 'shown in the following Table 1-1'BThe reaction time of the second step is 0.1 to 1.5 hours,
TABLE 1
TABLE 1-1
。
20. The method for producing a nitrile as claimed in claim 19, wherein in the first step, the upper limit of the reaction temperature is TA max-5℃、TA max-10℃、TA max-15 ℃ or TA max-20 ℃ of which TA maxRefer to said TAUpper limit values in said table 1.
21. The method for producing a nitrile as defined in claim 19, wherein when said second step is carried out in an open reaction system or under pressure, the upper limit of the reaction temperature is TB max-5℃、TB max-10℃、TB max-15 ℃ or TB max-20 ℃ of which TB maxRefer to said TBUpper limit values in said table 1.
22. The process for producing a nitrile as claimed in claim 19, wherein when the second step is carried out under reduced pressure, the upper limit of the reaction temperature is T'B max-5℃、T'B max-10℃、T'B max-15 ℃ or T'B max-20 ℃ of T'B maxIs referred to as T'BThe upper limit value in said Table 1-1.
23. The method for producing a nitrile as claimed in claim 1, wherein the group R is C6-12Aryl or C4-9A heteroaryl group.
24. The method for producing a nitrile as claimed in claim 1, wherein the first step obtains an ammonia-containing effluent at the same time as the amide intermediate product, and the ammonia-containing effluent is recycled to be supplied to the first step as a supplement to or a part of the ammonia source.
25. The method for producing a nitrile as claimed in claim 24, wherein the effluent containing ammonia is recycled to be supplied to the first step as a supplement to or a part of the ammonia source after being concentrated or dried.
26. The method for producing a nitrile as defined in claim 1, wherein said carboxylic acid source is of biological origin.
27. The method for producing a nitrile as defined in claim 1, wherein the carboxylic acid source is directly used as an industrially corresponding crude product.
28. The method for producing a nitrile as defined in claim 1, wherein said ammonia source is an industrial waste or an industrial by-product containing ammonia or said ammonia-producing substance.
29. The method for producing a nitrile as defined in claim 1, wherein the contacting is performed in a continuous, semi-continuous or batch manner.
30. The method for producing a nitrile as defined in claim 1, wherein the reaction in the closed reaction system is carried out under a pressure higher than ambient pressure.
31. The method for producing a nitrile as defined in claim 1, wherein the first step and the second step are carried out in the same reactor or different reactors.
32. The method for producing a nitrile as defined in claim 1, wherein the second step is carried out in an open reaction system or a closed reaction system.
33. The method for producing a nitrile as defined in claim 1, wherein no ammonia source is used in said second step.
34. The method for producing a nitrile as defined in claim 5, wherein the reduced pressure condition is achieved by maintaining the reaction system of the second step under a vacuum degree, and the vacuum degree has a value ranging from 5 to 1000 mbar.
35. The method for producing a nitrile as defined in claim 34, wherein the vacuum degree has a value within a range of 20 to 500 mbar.
36. The method for producing a nitrile as claimed in claim 34, wherein the vacuum degree has a value within the range of 50 to 250 mbar.
37. The method for producing a nitrile as defined in claim 5, wherein the reaction temperature T in said second step is controlled by said reduced pressure conditionBFurther reducing 40 to 130 ℃ and further reducing the reaction time of the second step by 40-80%.
38. The method for producing a nitrile as defined in claim 1, wherein the first step is performed under autogenous pressure.
39. The method for producing a nitrile as defined in claim 7, wherein the ammonia content of said aqueous ammonia solution is 10 to 30% by weight, and the ammonia-producing substance concentration of said ammonia-producing substance aqueous solution is 20% by weight to the saturated concentration.
40. The method for producing a nitrile as defined in claim 1, wherein the reaction time of said first step is 0.1 to 1.5 hours.
41. The method for producing a nitrile as defined in claim 1, wherein the reaction time of the first step is 0.2 to 0.5 hours.
42. The method for producing a nitrile as defined in claim 1, wherein when said second step is carried out in an open reaction system or under pressurized conditions, the reaction time of said second step is 0.3 to 2 hours.
43. The method for producing a nitrile as defined in claim 1, wherein when said second step is carried out in an open reaction system or under pressurized conditions, the reaction time of said second step is 0.4 to 1 hour.
44. The method for producing a nitrile as defined in claim 1, wherein when the second step is performed under reduced pressure, the reaction time of the second step is 0.2 to 0.8 hours.
45. The method for producing a nitrile as defined in claim 1, wherein when the second step is performed under reduced pressure, the reaction time of the second step is 0.3 to 0.5 hours.
46. A method for producing an amine, comprising the steps of:
the first step is as follows: producing a nitrile according to the production method of any one of claims 1 to 45; and
the second step: the nitrile obtained in the first step is hydrogenated to produce an amine.
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| KR20200103646A (en) * | 2017-12-27 | 2020-09-02 | 미쯔비시 가스 케미칼 컴파니, 인코포레이티드 | Dicyanocyclohexane, and method for producing bis(aminomethyl)cyclohexane |
| CN110396055B (en) * | 2019-08-31 | 2022-12-23 | 三门峡环宇生化科技有限公司 | Method for directly synthesizing parachlorobenzonitrile from parachlorobenzoic acid and urea |
| CN110396056A (en) * | 2019-08-31 | 2019-11-01 | 三门峡环宇生化科技有限公司 | A method of preparing m-chlorobenzene nitrile |
| CN110467543B (en) * | 2019-09-02 | 2022-06-07 | 三门峡环宇生化科技有限公司 | Preparation method of o-chlorobenzonitrile |
| CN112457213B (en) * | 2020-08-28 | 2022-08-30 | 鞍山七彩化学股份有限公司 | Catalytic synthesis method of p-aminobenzonitrile |
| CN113149903B (en) * | 2021-04-30 | 2023-02-10 | 安徽国星生物化学有限公司 | Method and device for synthesizing cyanopyridine |
| CN113620814B (en) * | 2021-08-10 | 2023-12-26 | 三明市海斯福化工有限责任公司 | Green preparation method of 2, 2-bis (4-aminophenyl) hexafluoropropane |
| CN115043749B (en) * | 2022-06-08 | 2023-06-27 | 东华大学 | Preparation method of diamide diol |
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| DE3923979A1 (en) * | 1989-07-20 | 1991-01-24 | Merck Patent Gmbh | METHOD FOR PRODUCING AROMATIC NITRILES |
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| CN1210852A (en) * | 1997-08-06 | 1999-03-17 | 东丽株式会社 | Process for producing nitrile |
| JP2009213975A (en) * | 2008-03-07 | 2009-09-24 | Tomita Pharmaceutical Co Ltd | Amide dehydration catalyst and method for manufacturing nitrile using the same |
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