CN102731357B - Preparation method of high purity N,N'-dicyclohexylthiourea - Google Patents
Preparation method of high purity N,N'-dicyclohexylthiourea Download PDFInfo
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- CN102731357B CN102731357B CN201210227941.XA CN201210227941A CN102731357B CN 102731357 B CN102731357 B CN 102731357B CN 201210227941 A CN201210227941 A CN 201210227941A CN 102731357 B CN102731357 B CN 102731357B
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Abstract
The invention provides a preparation method of high purity N,N'-dicyclohexylthiourea. The method comprises the following steps:1) mixing water and cyclohexylamine, then adding carbon disulfide in a dropwise manner at a temperature of 0-40 DEG C for 1-3 hours, controlling the temperature to 0-40 DEG C and continuously carrying out the reaction for 1-3 hours, wherein a weight ratio of the water to the cyclohexylamine is 2.5 to 3.8:1, and a weight ratio of the carbon disulfide to the cyclohexylamine is 0.3 to 0.45:1; 2) and carrying out filtration to remove the mother liquor to obtain an intermediate salt, and carrying out vacuum hydrogen sulfide removing on the under intermediate salt to obtain the N,N'-dicyclohexyl thiourea. With the technical scheme, disadvantages of flammability and explosiveness, and high cost of the organic solvent are avoided. Yield of the product provided in the invention is greater than 99%, and purity is greater than 99.5%. With the method, the same effect with using an organic solvent is realized, and the mother liquor can be reused, such that the organic solvent is wholly substituted and no waste liquid is discharged. According to the invention, by using the technology of vacuum hydrogen sulfide removing at the low temperature, energy consumption is lowered and removal efficiency of removing the hydrogen sulfide is guaranteed.
Description
Technical field
The present invention relates to a kind of preparation method of biological polypeptide condensing agent intermediate, particularly a kind of high purity N, the preparation method of N '-dicyclohexyl thiourea.
Background technology
At present domestic and international large-scale production N, the method of N '-dicyclohexyl thiourea is all reacted hexahydroaniline and dithiocarbonic anhydride to obtain under aromatic hydrocarbon solvent (as dimethylbenzene, benzene, toluene etc.) exists, although this method can be carried out industrial production, but its shortcoming is obvious, mainly: 1, solvent for use is all height ignition control compounds, and security is difficult to guarantee; 2, solvent toxicity used is larger; 3, solvent used easily loss in process of production, cost is higher.
J. Org.Chem., 1999,64(3): pp 1029-1032 discloses that to take hexahydroaniline and dithiocarbonic anhydride be raw material, zinc oxide and aluminum oxide are catalyzer, take water as solvent, under normal pressure or microwave condition, generate N, the method for N '-dicyclohexyl thiourea, but the shortcoming of the method is not to be suitable for suitability for industrialized production.
J. Org. Chem., 2010,75 (7), pp 2327 – 2332 disclose that to take corresponding amine and dithiocarbonic anhydride be raw material, sodium hydroxide is acid binding agent, take water as solvent, under reflux conditions generates and the method for substituting thioureido, but the shortcoming of the method is, complex operation, needs after having reacted with an organic solvent carrying out purifying after extraction product in acid He after sodium hydroxide, and yield is up to 90%, only be suitable for laboratory small-scale production, be not suitable for suitability for industrialized production.
The 26th the 6th phase of volume of < < Speciality Petrochemicals > >, 25-26 page, discloses that to take hexahydroaniline and dithiocarbonic anhydride be raw material, take water as solvent, 40
oc generates N, the method of N '-dicyclohexyl thiourea, but the shortcoming of the method is can not remove hydrogen sulfide completely under pure water phase condition, make its yield lower (being up to 93%), and security incident not exclusively very easily appears in hydrogen sulfide stripping when suitability for industrialized production, be therefore not suitable for suitability for industrialized production.
Summary of the invention
For there is above problem in prior art, the invention provides a kind of production technique reasonable, simple to operate and can suitability for industrialized production N, the preparation method of N '-dicyclohexyl thiourea.Below synthesis process of the present invention:
Its technical scheme comprises the following steps:
1) first water and hexahydroaniline are mixed, then at 0-40 ℃, drip dithiocarbonic anhydride, time for adding is 1-3 hour, drips off rear temperature control 0-40 ℃ and continues reaction 1-3 hour; The mass ratio of described water and hexahydroaniline is 2.5～3.8:1, and described dithiocarbonic anhydride and hexahydroaniline mass ratio are 0.3～0.45:1;
2) remove by filter after mother liquor, the intermediate salt obtaining obtains N after vacuum removal hydrogen sulfide, N '-dicyclohexyl thiourea.
Described step 2) in vacuum removal hydrogen sulfide, control vacuum tightness-0.03～-0.1MPa, temperature 50
oc～100
oc, time 1-5 hour.
Described step 2) mother liquor returns to step 1) recycled.
Pass through the technical program, the beneficial effect of obtaining is: make water as solvent, removed the shortcoming that organic solvent is inflammable and explosive, cost is high from, yield is greater than 99% simultaneously, and purity is greater than 99.5%, has realized and with an organic solvent same effect, and circulating mother liquor can recycle always, substituted organic solvent completely, Zero discharge, is a kind of friendly process; Use cryogenic vacuum to remove the technology of hydrogen sulfide, reduced energy consumption, saved cost, guaranteed the removal efficiency of hydrogen sulfide simultaneously.
Embodiment
Embodiment 1:
In reactor, add aqueous solvent 500kg, hexahydroaniline 200kg, starts to stir, and is warming up to 25 ℃, starts to drip dithiocarbonic anhydride 82 kg, controls time for adding 2h, and controls temperature at 25-30 ℃; Dropwise and continue, at 25-30 ℃ of insulation 1h, to filter after completion of the reaction, after the intermediate salt solid collection after filtration, again drop in reactor, open vacuum valve, remain on-0.05MPa of negative pressure of vacuum, is warming up to 90
odry 3 hours of C, removes hydrogen sulfide, obtains N, N '-dicyclohexyl thiourea product 241kg, yield 99.14%, purity 99.68%.
Mother liquid obtainedly in 10 reaction cycle, reuse in the back, do not need any processing, on average can obtain product 241.55kg, yield 99.36%.
| Recycling Mother Solution number of times | Product weight/kg | Product yield/% | Purity/% |
| 0 | 241 | 99.14 | 99.68 |
| 1 | 241 | 99.14 | 99.55 |
| 2 | 243 | 99.96 | 99.51 |
| 3 | 241 | 99.14 | 99.55 |
| 4 | 242 | 99.55 | 99.67 |
| 5 | 241 | 99.14 | 99.55 |
| 6 | 241 | 99.14 | 99.53 |
| 7 | 241 | 99.14 | 99.54 |
| 8 | 241 | 99.14 | 99.50 |
| 9 | 243 | 99.96 | 99.58 |
| 10 | 242 | 99.55 | 99.50 |
| Add up to | 2657 | 99.36 | 99.62 |
Embodiment 2:
In reactor, add aqueous solvent 500kg, hexahydroaniline 200kg, starts to stir, and is cooled to 10 ℃, starts to drip dithiocarbonic anhydride 80 kg, controls time for adding 3h, and controls temperature at 10-15 ℃; Dropwise and continue, at 10-15 ℃ of insulation 1h, to filter after completion of the reaction, after the intermediate salt solid collection after filtration, again drop in reactor, open vacuum valve, remain on-0.03MPa of negative pressure of vacuum, is warming up to 60
odry 5 hours of C, removes hydrogen sulfide, obtains N, N '-dicyclohexyl thiourea product 240.3kg, yield 99.08%, purity 99.56 %.
Embodiment 3:
In reactor, add aqueous solvent 500kg, hexahydroaniline 160kg, starts to stir, and is warming up to 30 ℃, starts to drip dithiocarbonic anhydride 68 kg, controls time for adding 1.5h, and controls temperature at 30-40 ℃; Dropwise and continue, at 25-30 ℃ of insulation 2h, to filter after completion of the reaction, after the intermediate salt solid collection after filtration, again drop in reactor, open vacuum valve, remain on-0.07MPa of negative pressure of vacuum, is warming up to 80
odry 2 hours of C, removes hydrogen sulfide, obtains N, N '-dicyclohexyl thiourea product 192.3kg, yield 99.08%, purity 99.56%.
Embodiment 4:
In reactor, add aqueous solvent 550kg, hexahydroaniline 160kg, starts to stir, and is cooled to 0 ℃, starts to drip dithiocarbonic anhydride 83kg, controls time for adding 3h, and controls temperature at 0-10 ℃; Dropwise and continue, at 0-10 ℃ of insulation 1.5h, to filter after completion of the reaction, after the intermediate salt solid collection after filtration, again drop in reactor, open vacuum valve, remain on-0.1MPa of negative pressure of vacuum, is warming up to 100
odry 2 hours of C, removes hydrogen sulfide, obtains N, N '-dicyclohexyl thiourea product 192.5kg, yield 99.16%, purity 99.58%.
Embodiment 5:
In reactor, add aqueous solvent 580kg, hexahydroaniline 160kg, starts to stir, and is cooled to 0 ℃, starts to drip dithiocarbonic anhydride 68kg, controls time for adding 1.5h, and controls temperature at 0-10 ℃; Dropwise and continue, at 0-10 ℃ of insulation 1.8h, to filter after completion of the reaction, after the intermediate salt solid collection after filtration, again drop in reactor, open vacuum valve, remain on-0.06MPa of negative pressure of vacuum, is warming up to 75
odry 2.5 hours of C, removes hydrogen sulfide, obtains N, N '-dicyclohexyl thiourea product 192.2kg, yield 99.03%, purity 99.50%.
Embodiment 6
In reactor, add aqueous solvent 600kg, hexahydroaniline 160kg, starts to stir, and is cooled to 0 ℃, starts to drip dithiocarbonic anhydride 80kg, controls time for adding 1h, and controls temperature at 0-10 ℃; Dropwise and continue, at 0-10 ℃ of insulation 1h, to filter after completion of the reaction, after the intermediate salt solid collection after filtration, again drop in reactor, open vacuum valve, remain on-0.03MPa of negative pressure of vacuum, is warming up to 50
odry 5 hours of C, removes hydrogen sulfide, obtains N, N '-dicyclohexyl thiourea product 192.6kg, yield 99.00%, purity 99.60%.
Embodiment 7
In reactor, add aqueous solvent 760kg, hexahydroaniline 200kg, starts to stir, and is warming up to 40 ℃, starts to drip dithiocarbonic anhydride 90kg, controls time for adding 3h, and controls temperature at 35-40 ℃; Dropwise and continue, at 35-40 ℃ of insulation 3h, to filter after completion of the reaction, after the intermediate salt solid collection after filtration, again drop in reactor, open vacuum valve, remain on-0.03MPa of negative pressure of vacuum, is warming up to 50
odry 5 hours of C, removes hydrogen sulfide, obtains N, N '-dicyclohexyl thiourea product 242kg, yield 99.55%, purity 99.67%.
Embodiment 8
In reactor, add aqueous solvent 500kg, hexahydroaniline 200kg, starts to stir, and is cooled to 15 ℃, starts to drip dithiocarbonic anhydride 60kg, controls time for adding 2h, and controls temperature at 15-25 ℃; Dropwise and continue, at 15-25 ℃ of insulation 3h, to filter after completion of the reaction, after the intermediate salt solid collection after filtration, again drop in reactor, open vacuum valve, remain on-0.1MPa of negative pressure of vacuum, is warming up to 80
odry 1 hour of C, removes hydrogen sulfide, obtains N, N '-dicyclohexyl thiourea product 241kg, yield 99.14%, purity 99.54%.
Below be only the part preferred embodiment of this programme; those skilled in the art can adopt other embodiment to realize completely within the protection domain of the technical program; aqueous solvent and encircle consumption, dropping temperature and the time of amine and dithiocarbonic anhydride; the pressure and the Heating temperature that after the reacted product of three filters, remove hydrogen sulfide all can make the appropriate adjustments, and at this, just do not repeat one by one.
Claims (1)
1. a N, the preparation method of N '-dicyclohexyl thiourea, is characterized in that: in reactor, add aqueous solvent 580kg, hexahydroaniline 160kg, starts to stir, and is cooled to 0 ℃, start to drip dithiocarbonic anhydride 68kg, control time for adding 1.5h, and control temperature at 0-10 ℃; Dropwise and continue, at 0-10 ℃ of insulation 1.8h, to filter after completion of the reaction, after the intermediate salt solid collection after filtration, again drop in reactor, open vacuum valve, remain on-0.06MPa of negative pressure of vacuum, is warming up to 75
odry 2.5 hours of C, removes hydrogen sulfide, obtains N, N '-dicyclohexyl thiourea product.
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104193653A (en) * | 2014-08-07 | 2014-12-10 | 山东汇海医药化工有限公司 | Novel synthesis method of N, N'-dicyclohexylcarbo-diimide |
| CN106430388A (en) * | 2016-08-24 | 2017-02-22 | 四川恒成钾盐化工有限公司 | Technology for removing and recovering hydrogen sulfide in brine |
| CN111978227A (en) * | 2020-09-04 | 2020-11-24 | 山西省化工研究所（有限公司） | Synthetic method of thiourea |
| CN113929607A (en) * | 2021-10-27 | 2022-01-14 | 鹤壁元昊化工有限公司 | Preparation method of aliphatic asymmetric thiourea compound |
| CN114702421B (en) * | 2022-04-15 | 2023-06-30 | 鹤壁中昊新材料科技有限公司 | Preparation method for synthesizing 1, 3-disubstituted symmetrical thiourea by taking primary amine as raw material |
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| US3708496A (en) * | 1970-03-28 | 1973-01-02 | H Kersten | Process for preparing 1,3-disubstituted symmetrical thioureas |
| EP0278890A2 (en) * | 1987-01-15 | 1988-08-17 | The Goodyear Tire & Rubber Company | Non-staining and slightly-staining antiozonants |
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| GB314542A (en) * | 1928-06-30 | 1930-08-07 | Ig Farbenindustrie Ag | Process for the manufacture of tri-substituted thioureas |
| GB678987A (en) * | 1949-07-11 | 1952-09-10 | Monsanto Chemicals | Improvements in or relating to derivatives of di(ª‰-phenethyl)-dithiocarbamic acid |
| GB839797A (en) * | 1958-04-14 | 1960-06-29 | Yorkshire Tar Distillers Ltd | Substituted thioureas and their use as pesticidal agents |
| JPS5716859A (en) * | 1980-07-04 | 1982-01-28 | Nippon Carbide Ind Co Ltd | Preparation of n,n'-di-substituted thiourea |
| JPS63254144A (en) * | 1987-04-10 | 1988-10-20 | Bridgestone Corp | Low thermogenic rubber composition |
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| US3708496A (en) * | 1970-03-28 | 1973-01-02 | H Kersten | Process for preparing 1,3-disubstituted symmetrical thioureas |
| EP0278890A2 (en) * | 1987-01-15 | 1988-08-17 | The Goodyear Tire & Rubber Company | Non-staining and slightly-staining antiozonants |
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| A Concise Synthesis of Substituted Thiourea Derivatives in;Mahagundappa R. Maddani 等;《J.Org.Chem》;20100304;第75卷(第7期);第2328页 * |
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Denomination of invention: Preparation of high purity n, n '- dicyclohexylthiourea Effective date of registration: 20211130 Granted publication date: 20140212 Pledgee: Dongying Hekou District sub branch of China Post Savings Bank Co.,Ltd. Pledgor: SHANDONG HUIHAI PHARMACEUTICAL& CHEMICAL Co.,Ltd. Registration number: Y2021980013568 |
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