CN101891653A - Clean production method of symmetric N,N'-disubstituted urea - Google Patents
Clean production method of symmetric N,N'-disubstituted urea Download PDFInfo
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- CN101891653A CN101891653A CN2009100151585A CN200910015158A CN101891653A CN 101891653 A CN101891653 A CN 101891653A CN 2009100151585 A CN2009100151585 A CN 2009100151585A CN 200910015158 A CN200910015158 A CN 200910015158A CN 101891653 A CN101891653 A CN 101891653A
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Abstract
The invention relates to a clean production method of symmetric N,N'-disubstituted urea, which is particularly applicable to production of N,N'-diphenylurea, N,N'-dicyclohexylurea and 4,4'-dinitro diphenyl urea. The clean production method comprises the steps of mixing mother liquor, amine and urea, recovering solvent, carrying out reaction, producing mixture containing the amine and the N,N'-disubstituted urea, using the solvent to carry out simple soaking or recrystallization on the mixture, separating, and obtaining the crystalline high-purity N,N'-disubstituted urea and the mother liquor, and the amine dissolved in the mother liquor naturally realizes the circulating reaction of the next production during the recovery process.
Description
Invention field: the present invention relates to a kind of symmetric N, the clean preparation method of N '-2-substituted carbamide, particularly suitable is N, N '-diphenyl urea, N, N '-dicyclohexylurea (DCU) and 4, the production of 4 '-dinitro diphenyl urea.
Background technology: to the N that takes by weighing, N '-2-substituted carbamide has extensive use owing to have its unique symmetrical structure in Chemical Manufacture.For example: N, N '-diphenyl urea (N, N '-Diphenylurea) have another name called diphenylurea can be used for synthetic herbicide and sterilant at pesticide industry, also the intermediate of useful as drug phenalgin sulfonic acid and preparation sulfa drugs can be used as the intermediate of producing phenyl urethan; N, N '-dicyclohexylurea (DCU) is preparation N, the intermediate of N '-dicyclohexylcarbodiimide; 4,4 '-dinitro diphenyl urea is the intermediate of dyestuff, medicine and veterinary drug.N, N '-2-substituted carbamide prior synthesizing method is direct or indirect raw material with hypertoxic phosgene, discharge a large amount of poisonous hydrogen chloride gas, seriously polluted, have major safety risks, now less employing, present N, N '-2-substituted carbamide synthetic mainly contains two kinds of methods: the one, and traditional amine method, this method are to be reacted in aqueous solution of hydrochloric acid and got by amine and urea, shortcoming content is low, yield is low, plant factor is low, waste water is many, it is big to separate the purification difficulty; Another kind method is to get with the reduction oxonation of nitro substituent, relatively has the advantage that raw material is easy to get, step is few, productive rate is high with traditional method, but catalyzer costliness, severe reaction conditions, catalyst recovery and N, the purification difficult of N '-2-substituted carbamide; Patent CN1440964A has introduced a kind of production phenylurea and N, the method for N '-diphenyl urea, but need repetitive operation in order to improve yield, and to use a large amount of water to make solvent, plant factor is low, waste water is many; It is that solvent promotes reaction to be prepared N with water that patent CN101279932A introduces row a kind of, the method for N '-dicyclohexylurea (DCU), and what obtain is cured article, productive rate 65～95%, 205～230 ℃ of fusing points; It is raw material with p-Nitroaniline and solid phosgene that patent CN1463965A has introduced a kind of, is solvent with ester, synthesizes 4 under the acid binding agent existence condition, the method for 4 '-dinitro diphenyl urea.U.S. Pat 5591883 has been mentioned in the process of producing dialkyl carbonate with amine and urea pyrolysis and has been produced N, the intermediate steps of N '-2-substituted carbamide and amine mixt, but there is not effective separation scheme and directly application, " Zhejiang Agricultural Univ's journal " 1995,21 (2): it is solvent that 214-216. replaces water with primary isoamyl alcohol, do not add catalyzer, with aniline and urea in 140～148 ℃ of heating reflux reactions, can make productive rate bring up to 88%, but the reaction times reaches 20h, " process engineering journal " 2008 the 8th the 3rd phases of volume are attempted N that aniline urea pyrolysis method is obtained, N '-diphenyl urea filters and the decompression separation method with taking separating of aniline mixture, but with regard to industrial-scale production may be difficult, because aniline and N, N '-diphenyl urea normally produce with pasty state or block, filtration is difficult to realize aniline and N, effective separation of N '-diphenyl urea, and because the boiling point of phenylamino is higher and the industrial condition of its activity decompression may require quite harsh.Do not find that up to now document, publication, patent are put down in writing relevant soaked in solvent or recrystallization reaches effective separation of amine, urea pyrolysis method synthetic N, N '-2-substituted carbamide and amine mixt, mother liquor dissolved amine has been realized the method for the circulating reaction of next production naturally in applying mechanically removal process.
Summary of the invention: the object of the present invention is to provide the symmetric N that a kind of technology is simple, reaction conditions is gentle, environmental protection is friendly, cost is low, plant factor is high, the production method of N '-2-substituted carbamide.
The present invention is achieved through the following technical solutions: with mother liquor, amine and urea at the reactor internal heating, reclaim solvent, also can after reclaiming the solvent end, add amine and urea again to mother liquor, and constantly promote temperature and begin until the reaction of amine and urea, produce a large amount of ammonia this moment, control reaction temperature and available various possible modes guarantee to make the ammonia of generation constantly to overflow reactor to promote the carrying out of reaction, obviously reduce or stop up to the generation of ammonia, obtain with symmetric N, N '-2-substituted carbamide and amine are main mixture; What obtain contains N, the mixture of N '-2-substituted carbamide and amine through after the fragmentation with solvent or with solvent after carry out fragmentation so that solid is loose, separate then, washing, drying obtain symmetric N, N '-2-substituted carbamide and the mother liquor that contains amine, also can obtain the higher symmetric N of purity by recrystallization with solvent, symmetrical urea of N '-two and the mother liquor that contains amine, mother liquor dissolved amine begin the next circulating reaction of producing in applying mechanically removal process.
Aforesaid amine can be selected from: aniline; fluorine-containing on the aromatic ring, chlorine, alkyl, aryl, nitro, alkoxyl group, aryloxy, alkylthio, arylthio, cyano group, N; amino, alkyl carbonyl, aromatic carbonyl, the alkyl sulphonyl that the N-dialkyl group replaces is not limited to the aniline of a substituted radical; contain or do not contain the hexahydroaniline that alkyl replaces; phenylhydrazine; cyclopentamine, methylphenylamine, N-ethylaniline.
The method of aforesaid immersion and recrystallization can be with liquid or solid-state form and solvent with the mixture of amine and 2-substituted carbamide, described solvent is under immersion or recrystallization condition reactant and resultant to be organic solvent inert, at least can and preferably alcohol, the halohydrocarbon of C1～C5, the more preferably extremely corresponding mother liquor of methyl alcohol, ethanol, chloroform, trichloroethane.
Aforesaid immersion and recrystallization temperature can be below the relevant pressure boiling points.
Aforesaid operating process can or select for use a kind of gas that is not limited in helium, neon, argon gas, nitrogen, the ammonia to protect, and what preferably use is nitrogen and ammonia.
Aforesaid operating process feeds intake first can be without mother liquor and the operation of reclaiming solvent.
Aforesaid method can be by using but is not limited to by rejecting organic impurity with activated carbon decolorizing, rejecting mechanical impurity by filtering, and the also available fresh solvent dissolution filter that feeds intake is first rejected mechanical impurity.
Advantage of the present invention:
(1) raw material is easy to get, does not have contaminated wastewater, and it is few to soak the solvent load that uses, the plant factor height.
(2) but the reaction atmospheric operation, without catalyzer.
(3) lack reaction time, the unit equipment production capacity is big.
(4) mother liquor and washings dissolved amine have been realized the round-robin reaction of next production, equipment and energy utilization rate height naturally in applying mechanically removal process.
(5) reaction conditions gentleness, the symmetric N of product, the selectivity height of N '-2-substituted carbamide, near 100%, the symmetric N of product, the yield height of N '-2-substituted carbamide, yield is near 100%.
(6) mixture to amine and 2-substituted carbamide just can obtain the symmetric N of highly purified crystallization through simply immersing and recrystallization, N '-2-substituted carbamide, the crystallization N that obtains after the immersion, the content of N '-2-substituted carbamide can reach 99%[HLPC] more than, and can get content near 100%[HLPC through a recrystallization] N, N '-2-substituted carbamide.
Embodiment: following with N, the example that is prepared as of N '-diphenyl urea is done nonrestrictive explanation to this programme.
Embodiment 1:
In the there-necked flask of 250ml, add 40g aniline, 5g urea; use nitrogen protection, extremely dissolving of heat temperature raising under whipped state, and have ammonia to produce; continue to heat up; the generation of ammonia also strengthens gradually, is warmed up to 170～190 ℃, and at 170～190 ℃ of insulation 90min; cool to 25 ℃ and carry out liquid-phase chromatographic analysis; conversion rate of urea 100%, N, the selectivity 99.6% of N '-diphenyl urea.Add the 50ml dehydrated alcohol, it is loose fully to be stirred to dope under the normal temperature, and pumping rate is used the 10ml absolute ethanol washing, drying, product N, N '-diphenyl urea content 99.61%, productive rate 95.1%.
Embodiment 2:
In the there-necked flask of 250ml, add the mixing mother liquor that embodiment 1 separates and washs; add 15ml aniline, 5g urea; stirring makes the urea dissolving; filter; filtrate is used nitrogen protection; heat temperature raising reclaims ethanol; be recycled to still liquid and stop to reclaim ethanol for about 140 ℃, continue to heat up, and the ammonia that produces is in time discharged reactor; be warmed up to 170～190 ℃; and, cool to 25 ℃ and carry out liquid-phase chromatographic analysis, conversion rate of urea 100% at 170～190 ℃ of insulation 90min; N, the selectivity 99.7% of N '-diphenyl urea.Add and reclaim ethanol 50ml, it is loose fully to be stirred to dope under the normal temperature, and pumping rate is used the 20ml absolute ethanol washing, drying, product N, N '-diphenyl urea content 99.67%, productive rate 100.4%.
Embodiment 3:
In the there-necked flask of 250ml, add the mixing mother liquor that embodiment 2 separates and washs; add 15ml aniline, 5g urea; add about 0.2g gac; in 50～60 ℃ of insulation 30min; filter; filtrate is used nitrogen protection in reactor, heat temperature raising reclaims ethanol, is recycled to still liquid and stops to reclaim ethanol for about 140 ℃; continue to heat up; and the ammonia that produces in time discharged reactor, be warmed up to 170～190 ℃, and at 170～190 ℃ of insulation 90min; cool to 25 ℃ and carry out liquid-phase chromatographic analysis; conversion rate of urea 100%, N, the selectivity 100% of N '-diphenyl urea.Add 50ml and reclaim ethanol, it is loose fully to be stirred to dope under the normal temperature, and pumping rate is used the 20ml absolute ethanol washing, drying, product N, N '-diphenyl urea content 99.64%, productive rate 99.3%.
Embodiment 4:
In the there-necked flask of 250ml, add 25g aniline 3g urea; use nitrogen protection; extremely dissolving of heat temperature raising under whipped state, and have ammonia to produce, continue to heat up; the generation of ammonia also strengthens gradually; be warmed up to 170～190 ℃, and, cool to 30 ℃ and add the 150ml dehydrated alcohol at 170～190 ℃ of insulation 90min; it is loose fully to be stirred to dope; transfer in the reaction flask of 500ml and add 200ml ethanol, add a little gac reflux 30min, pumping rate; the filtrate crystallisation by cooling; separate solid 10ml absolute ethanol washing, drying, product N; N '-diphenyl urea content 99.91%, productive rate 96.5%.
Embodiment 5:
The mother liquor 150ml heating recovery ethanol that in the there-necked flask of 250ml, adds embodiment 4, and with the adding gradually under the recovery state of remaining mother liquor, be recycled to about 140 ℃ and stop to reclaim ethanol, add 9ml aniline, 3g urea, continue to heat up, and the ammonia that produces in time discharged reactor, be warmed up to 170～190 ℃, and, cool to 80 ℃ and add 150ml ethanol at 170～190 ℃ of insulation 90min, it is loose fully to be stirred to dope, transfer in the reaction flask of 500ml and add 200ml ethanol, add 0.1g gac reflux 30min, pumping rate, the filtrate crystallisation by cooling, separate solid 10ml absolute ethanol washing, drying, product N, N '-diphenyl urea content 99.96%, productive rate 101.7%.
Claims (7)
1. symmetric N, the clean preparation method of N '-2-substituted carbamide, it is characterized in that: isolate N, the mother liquor that obtains behind N '-2-substituted carbamide can reclaim solvent earlier, then residuum is produced with amine, urea mixing intensification deamination and contain amine and N, the mixture of N '-2-substituted carbamide, or mother liquor directly is blended in amine, urea reclaims solvent Shu Houzai lifting temperature of reaction and carry out deamination reaction and obtain containing amine and N, the mixture of N '-2-substituted carbamide.
2. as condition 1 described method, it is characterized in that: isolate N, mother liquor behind N '-2-substituted carbamide is meant and contains amine and symmetric N with including but not limited to by what feature 1 method obtained, the mixture of N '-2-substituted carbamide, take but be not limited to soaked in solvent or with the method for solvent recrystallization, isolating symmetric N, the solution that contains amine that produces in N '-2-substituted carbamide crystalline process.
3. according to each method in the aforementioned claim; described amine can be selected from: aniline; fluorine-containing on the aromatic ring, chlorine, alkyl, aryl, nitro, alkoxyl group, aryloxy, alkylthio, arylthio, cyano group, N; amino, alkyl carbonyl, aromatic carbonyl, the alkyl sulphonyl that the N-dialkyl group replaces is not limited to the aniline of a substituted radical; contain or do not contain the hexahydroaniline that alkyl replaces, phenylhydrazine, cyclopentamine; methylphenylamine, N-ethylaniline.
4. according to each method in the aforementioned claim, to soak and the method for recrystallization can be will contain the mixture of amine and 2-substituted carbamide with liquid or solid-state form and solvent, immersion and recrystallization temperature can be below the boiling points of relevant pressure solvent.
5. according to each method in the aforementioned claim, described solvent be soak or the recrystallization condition under reactant and resultant are organic solvent inert, alcohol, halohydrocarbon that can and preferably select C1～C5 at least for use is mother liquor extremely.
6. according to each method in the aforementioned claim, reaction can or be selected for use at helium, neon, argon gas, nitrogen, ammonia and is not limited to carry out under a kind of gas shield.
7. according to each method in the aforementioned claim, the processing of can decolouring to the mixed solution of mother liquor or mother liquor and amine, urea.
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| CN2009100151585A CN101891653A (en) | 2009-05-19 | 2009-05-19 | Clean production method of symmetric N,N'-disubstituted urea |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103232371A (en) * | 2013-04-26 | 2013-08-07 | 黎明化工研究设计院有限责任公司 | Method for preparing N-methyl-N', N'-diphenylcarbamide |
| CN104529832A (en) * | 2014-11-18 | 2015-04-22 | 江苏泰仓农化有限公司 | Production technology of N-cyclohexylurea |
| CN106008274A (en) * | 2016-06-03 | 2016-10-12 | 绍兴文理学院 | Preparation method of N,N'-dicyclohexylurea |
| CN109503431A (en) * | 2018-12-28 | 2019-03-22 | 山东广浦生物科技有限公司 | A kind of synthetic method of N, N- dicyclohexylurea (DCU) |
| CN112924612A (en) * | 2019-12-06 | 2021-06-08 | 天津药物研究院有限公司 | Method for determining content of impurity C in gliquidone |
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| EP0437258A1 (en) * | 1990-01-12 | 1991-07-17 | Nkk Corporation | Method of manufacturing aromatic urethane |
| CN1440964A (en) * | 2003-03-28 | 2003-09-10 | 中国科学院山西煤炭化学研究所 | Production process of phenyl carbamide and/or diphenyl carbamide |
| CN101407477A (en) * | 2007-10-10 | 2009-04-15 | 中国石油天然气股份有限公司 | Method for synthesizing diphenylurea from urea and aniline |
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2009
- 2009-05-19 CN CN2009100151585A patent/CN101891653A/en active Pending
Patent Citations (3)
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| EP0437258A1 (en) * | 1990-01-12 | 1991-07-17 | Nkk Corporation | Method of manufacturing aromatic urethane |
| CN1440964A (en) * | 2003-03-28 | 2003-09-10 | 中国科学院山西煤炭化学研究所 | Production process of phenyl carbamide and/or diphenyl carbamide |
| CN101407477A (en) * | 2007-10-10 | 2009-04-15 | 中国石油天然气股份有限公司 | Method for synthesizing diphenylurea from urea and aniline |
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| 游志敏等: "尿素法常压非催化合成N,N"-二苯基脲", 《过程工程学报》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103232371A (en) * | 2013-04-26 | 2013-08-07 | 黎明化工研究设计院有限责任公司 | Method for preparing N-methyl-N', N'-diphenylcarbamide |
| CN103232371B (en) * | 2013-04-26 | 2014-11-26 | 黎明化工研究设计院有限责任公司 | Method for preparing N-methyl-N', N'-diphenylcarbamide |
| CN104529832A (en) * | 2014-11-18 | 2015-04-22 | 江苏泰仓农化有限公司 | Production technology of N-cyclohexylurea |
| CN106008274A (en) * | 2016-06-03 | 2016-10-12 | 绍兴文理学院 | Preparation method of N,N'-dicyclohexylurea |
| CN109503431A (en) * | 2018-12-28 | 2019-03-22 | 山东广浦生物科技有限公司 | A kind of synthetic method of N, N- dicyclohexylurea (DCU) |
| CN109503431B (en) * | 2018-12-28 | 2021-04-06 | 山东广浦生物科技有限公司 | Synthesis method of N, N-dicyclohexylurea |
| CN112924612A (en) * | 2019-12-06 | 2021-06-08 | 天津药物研究院有限公司 | Method for determining content of impurity C in gliquidone |
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Application publication date: 20101124 |