CN107011381A - The control method of objectionable impurities in pirimiphos-methyl synthesis - Google Patents
The control method of objectionable impurities in pirimiphos-methyl synthesis Download PDFInfo
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- CN107011381A CN107011381A CN201710290360.3A CN201710290360A CN107011381A CN 107011381 A CN107011381 A CN 107011381A CN 201710290360 A CN201710290360 A CN 201710290360A CN 107011381 A CN107011381 A CN 107011381A
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- Prior art keywords
- methyl
- pirimiphos
- objectionable impurities
- control method
- diethylamino
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- 239000005924 Pirimiphos-methyl Substances 0.000 title claims abstract description 65
- 239000012535 impurity Substances 0.000 title claims abstract description 65
- QHOQHJPRIBSPCY-UHFFFAOYSA-N pirimiphos-methyl Chemical group CCN(CC)C1=NC(C)=CC(OP(=S)(OC)OC)=N1 QHOQHJPRIBSPCY-UHFFFAOYSA-N 0.000 title claims abstract description 65
- 238000000034 method Methods 0.000 title claims abstract description 43
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 33
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 33
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- -1 methyl thiotep Chemical compound 0.000 claims abstract description 28
- 239000003054 catalyst Substances 0.000 claims abstract description 15
- 229910052751 metal Inorganic materials 0.000 claims abstract description 11
- 239000002184 metal Substances 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 238000006482 condensation reaction Methods 0.000 claims abstract description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 57
- 229910052757 nitrogen Inorganic materials 0.000 claims description 48
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 45
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 34
- ZENSUSNKIIKEDV-UHFFFAOYSA-N 3-(diethylamino)-4-methyl-1,2-dihydropyrimidin-6-one Chemical compound C(C)N(N1CN=C(C=C1C)O)CC ZENSUSNKIIKEDV-UHFFFAOYSA-N 0.000 claims description 20
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 10
- 239000001103 potassium chloride Substances 0.000 claims description 10
- 235000011164 potassium chloride Nutrition 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 6
- NQCPECCCWDWTJJ-UHFFFAOYSA-N 2-diethylamino-6-methylpyrimidin-4(1H)-one Chemical class CCN(CC)C1=NC(=O)C=C(C)N1 NQCPECCCWDWTJJ-UHFFFAOYSA-N 0.000 claims description 5
- 238000004807 desolvation Methods 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 4
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 4
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 4
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 claims description 4
- 229940043265 methyl isobutyl ketone Drugs 0.000 claims description 4
- 229940050176 methyl chloride Drugs 0.000 claims description 2
- 238000012805 post-processing Methods 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 2
- UGOLAPHJCTVIEW-UHFFFAOYSA-N chloro-dimethyl-sulfanylidene-$l^{5}-phosphane Chemical class CP(C)(Cl)=S UGOLAPHJCTVIEW-UHFFFAOYSA-N 0.000 abstract 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 abstract 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 238000001816 cooling Methods 0.000 description 14
- 239000002253 acid Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 9
- 239000002994 raw material Substances 0.000 description 9
- YHUUZKCUQVILTK-UHFFFAOYSA-N 2,3-dimethylpyridin-4-amine Chemical compound CC1=NC=CC(N)=C1C YHUUZKCUQVILTK-UHFFFAOYSA-N 0.000 description 8
- NBAUXRCSDWYKRP-UHFFFAOYSA-N dimethyl phosphorochloridothioate Chemical compound COP(Cl)(=O)SC NBAUXRCSDWYKRP-UHFFFAOYSA-N 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- WGKCEIRLWOKLOE-UHFFFAOYSA-N [P].CC1=NC=CC=N1 Chemical compound [P].CC1=NC=CC=N1 WGKCEIRLWOKLOE-UHFFFAOYSA-N 0.000 description 7
- 239000011230 binding agent Substances 0.000 description 7
- 239000012065 filter cake Substances 0.000 description 7
- 238000004817 gas chromatography Methods 0.000 description 7
- 238000001556 precipitation Methods 0.000 description 7
- QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- 239000011574 phosphorus Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 3
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 150000003230 pyrimidines Chemical class 0.000 description 3
- 230000036632 reaction speed Effects 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 208000031320 Teratogenesis Diseases 0.000 description 2
- WTUNGUOZHBRADH-UHFFFAOYSA-N [methoxy(methylsulfanyl)phosphoryl]oxymethane Chemical compound COP(=O)(OC)SC WTUNGUOZHBRADH-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- XWSLYQXUTWUIKM-UHFFFAOYSA-N trimethoxy(sulfanylidene)-$l^{5}-phosphane Chemical compound COP(=S)(OC)OC XWSLYQXUTWUIKM-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- FGGJSYHDZAQGEL-UHFFFAOYSA-N 2-(ethylamino)-6-methyl-1h-pyrimidin-4-one Chemical class CCNC1=NC(C)=CC(O)=N1 FGGJSYHDZAQGEL-UHFFFAOYSA-N 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- ZSUFBRGARNXNBX-UHFFFAOYSA-N [P].C1=CC=NC=C1 Chemical compound [P].C1=CC=NC=C1 ZSUFBRGARNXNBX-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960004979 fampridine Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000011356 non-aqueous organic solvent Substances 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- CHWRSCGUEQEHOH-UHFFFAOYSA-N potassium oxide Chemical compound [O-2].[K+].[K+] CHWRSCGUEQEHOH-UHFFFAOYSA-N 0.000 description 1
- 229910001950 potassium oxide Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6509—Six-membered rings
- C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
Abstract
The invention discloses the control method of objectionable impurities in a kind of synthesis of pirimiphos-methyl, comprise the following steps：By 2 N, the hydroxy pyrimidine metal salt of 6 methyl of N diethylaminos 4 and catalyst are added in organic solvent, then O is added dropwise, and O dimethyl thiophosphoryl chlorides carry out condensation reaction, and gained reaction solution is post-treated, obtain pirimiphos-methyl, complete the control of objectionable impurities.The control method of objectionable impurities can effectively control the content of objectionable impurities in pirimiphos-methyl synthesis, and the amount of objectionable impurities methyl thiotep (＜ 0.06%) and different pirimiphos-methyl (＜ 0.2%) is far below FAO limitation concentration standards.
Description
Technical field
The invention belongs to objectionable impurities in hygienic medication preparing technical field, more particularly to a kind of synthesis of pirimiphos-methyl
Control method.
Background technology
Pirimiphos-methyl is low toxicity (LD50 is 2050mg/kg), efficiently (dosage of grain warehousing be 8ppm), low residual
Insecticide is stayed, is the grain warehousing pesticide species that FAO (Food and Agriculture Organization of the United Nation) (FAO) recommends to the utmost, and family is used as in developed country
Hygienic medication is used.
Although pirimiphos-methyl, which belongs to low toxic pesticide, to be widely used, FAO is to pirimiphos-methyl active compound within 2007
In carcinogenic teratogenesis objectionable impurities O, O- dimethyl thiophosphoryl chloride (Methochloride), O, O, S- trimethyl phosphordithiic acid
The content of ester, O, O, S- trimethyl phosphorothioates, O, O, O- trimethyl phosphorothioates and different pirimiphos-methyl, which has, strictly will
(control is below 0.5%) is asked, what other were not included in has hypertoxic impurity to be each necessarily less than 0.1% to people, animal.Although methyl is phonetic
The main content of pyridine phosphorus active compound is more than 98%, but if any of the above objectionable impurities are higher than limit index, can not also obtain
The agriculture chemical registration and sale of European and American developed countries.Because Light absorbing impurty index is excessively harsh, the product of agrochemical enterprise of China production
It can not still reach American-European countries's purchase requirement at present.
The optimal industrial method of pirimiphos-methyl using Methochloride and 2-N, N- diethylamino -6- methyl -
4- hydroxy pyrimidines are condensed, and desolvation is evaporated in vacuo again after reaction solution washing obtains product.Because pirimiphos-methyl has boiling point
Bring into and contract in the properties such as height, poorly water-soluble, heat endurance poor (being easily decomposed into the different pirimiphos-methyl of objectionable impurities), primary raw material
Closing the impurity of the newly-generated poorly water-soluble of reaction can stay in the product, cause objectionable impurities in active compound to exceed limit standard.Through
Cross O in analysis, above-mentioned objectionable impurities, O, S- trimethyls phosphorodithioate, O, O, S- trimethyl phosphorothioates, O, O, O- tri-
Methylphosphorothioate can use the Methochloride of high-quality (it is required that each both from key intermediate Methochloride
Impurity content avoids such contaminant overstandard less than 0.1%)；Reacting the Methochloride not remained thoroughly can also be by changing
The rate of charge of raw material realizes strict control；But the impurity such as different pirimiphos-methyl and methyl thiotep generated during the course of the reaction
How to control in relatively low concentration, never pertinent literature introduction.
ZL200910043946.5 discloses Methochloride and 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidines
For raw material, sodium hydroxide is acid binding agent, and toluene and water are solvent, and by adding hydrolysis inhibitor and catalyst, are effectively suppressed
O, the hydrolysis of O- dimethyl thiophosphoryl chlorides realizes the preparation of high-purity odorless pirimiphos-methyl.Although the patent is by adding
The generation of objectionable impurities can be greatly reduced by entering hydrolysis inhibitor and catalyst, but due to using water and sodium hydroxide, it is impossible to keep away
Exempt to generate methyl thiotep (thiopyrophosphate of O, O, O, O- tetramethyl two) of people, animal severe toxicity and teratogenesis etc., first in product
Base thiotep content 0.11%~0.37%, and O, O, O- trimethyl phosphorothioate are all higher than 1%, this two impurity indexs
It is unable to reach FAO standards.
Nie Ping etc. (fine-chemical intermediate, the 2010, the 1st phase) uses Methochloride and 2-N, N- diethylaminos -6-
Methyl -4- hydroxy pyrimidines are raw material, and sodium hydroxide is acid binding agent, and toluene is solvent, add sodium sulphate as hydrolysis inhibitor, instead
25~35 DEG C of temperature is answered, the pirimiphos-methyl of content 99% is obtained, yield 94% is not controlled to related objectionable impurities.By
Equimolar water is produced in the reaction, adding hydrolysis inhibitor can only reduce but not be avoided that methyl thiotep is formed.
Road sun waits (Sichuan chemical industry, the 2005, the 6th phase) to use Methochloride and 2-N, N- diethylamino -6- methyl -4-
Hydroxy pyrimidine is raw material, and potassium phosphate is acid binding agent, and ethyl acetate is solvent, and 40~50 DEG C of reaction temperature obtains content 95%
Pirimiphos-methyl, yield 94% is not controlled to related objectionable impurities.
Zhou Yukun etc. (agricultural chemicals, the 2002, the 1st phase) uses Methochloride and 2-N, N- diethylamino -6- methyl -4- hydroxyls
Yl pyrimidines are raw material, and potassium carbonate is acid binding agent, and ethyl acetate is solvent, and 45~50 DEG C of reaction temperature obtains content 85-90%'s
Pirimiphos-methyl, yield 94% is not controlled to related objectionable impurities.
Shen Delong etc. (Guangdong chemical industry, the 2001, the 3rd phase) use Methochloride and 2-N, N- diethylamino -6- methyl -
4- hydroxy pyrimidines are raw material, and sodium hydroxide is acid binding agent, and room temperature reaction obtains pirimiphos-methyl, and yield 93% does not have to correlation
Evil impurity is controlled.
Nie Ping etc. (Hubei Chemical, 1998, supplementary issue) uses Methochloride and 2-N, N- diethylamino -6- methyl -4-
Hydroxy pyrimidine is raw material, and potassium hydroxide is acid binding agent, and toluene is solvent, and 70~75 DEG C of reaction temperature obtains the first of content 95%
Yl pyrimidines phosphorus, yield 96% is not controlled to related objectionable impurities.
O in current 99% Methochloride industrial goods, O, S- trimethyls phosphorodithioate, O, O, the thio phosphorus of S- trimethyls
Acid esters, O, O, O- trimethyl phosphorothioates etc. can be less than 0.1%, therefore substantially may be used by such objectionable impurities that raw material is brought into
To be controlled.Although pirimiphos-methyl synthesis is fairly simple, to realize that pirimiphos-methyl product quality reaches FAO requirement
And it is in line with international standards, it is necessary to during the course of the reaction as far as possible avoid produce the objectionable impurities such as methyl thiotep and different pirimiphos-methyl or
Controlled under defined limitation level.It is therefore desirable to develop a kind of pirimiphos-methyl that can effectively control objectionable impurities
Synthetic method.
The content of the invention
The technical problem to be solved in the present invention is to overcome the deficiencies in the prior art to have in being synthesized there is provided a kind of pirimiphos-methyl
The amount of the control method, wherein objectionable impurities methyl thiotep (＜ 0.06%) and different pirimiphos-methyl (＜ 0.2%) of evil impurity
Far below FAO limitation concentration standards.
The invention thinking of the present invention is the original produced based on the analysis objectionable impurities such as methyl thiotep and different pirimiphos-methyl
Cause, and take corresponding means to suppress its generation：
1. Methochloride generation impurity methyl thiotep in water presence (as shown in formula (1))：Use sodium hydroxide, hydrogen
In potassium oxide, sodium carbonate, potassium carbonate, potassium phosphate etc. and 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine salification process
It can not avoid that water can be generated, and use water as the generation of the more favourable impurity methyl thiotep of solvent of above-mentioned inorganic base.
When particularly there is inorganic strong alkali and higher reaction temperature in system, above formula reaction generation can be accelerated, added neutral
Hydrolysis inhibitor can not avoid the reaction occur.The present invention is by the way that first by 2-N, N- diethylamino -6- methyl -4- hydroxyls are phonetic
Pyridine prepares corresponding 2-N, N- diethylaminos -6- methyl -4- hydroxy pyrimidines sodium salt or potassium with sodium hydroxide or potassium hydroxide
Salt, reacts (as shown in formula (2)) in the organic solvents such as toluene with Methochloride, due to nothing in reaction system again after drying
Water or water are few, therefore can avoid producing methyl thiotep or the control of its content in extremely low level.
2. pirimiphos-methyl is heated or acid condition under (Methochloride is highly acid material) easily reset that to produce impurity different
Pirimiphos-methyl (as shown in formula (3)), thus take relatively low reaction temperature and avoid Methochloride from excessively may be used in systems
To be prevented effectively from the generation of the different pirimiphos-methyl of impurity.
Applicant has found in early-stage Study, although use 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sodium salts
Or sylvite replaces sodium hydroxide or potassium hydroxide acid binding agent that methyl thiotep can be avoided to produce, but due to sodium salt or the alkali of sylvite
Property it is low compared with sodium hydroxide and potassium hydroxide, its reaction speed with Methochloride is also relatively slow, particularly reacts later stage drop
The Methochloride localized clusters of addition system, can cause to produce more different pirimiphos-methyl.Therefore in relatively low reaction temperature
Degree is lower to ensure reaction speed, and the catalyst for being conducive to non-homogeneous condensation to react need to be added in reaction system.
In order to solve the above technical problems, the present invention uses following technical scheme：
The control method of objectionable impurities, comprises the following steps in a kind of pirimiphos-methyl synthesis：
By 2-N, N- diethylaminos -6- methyl -4- hydroxy pyrimidines metal salt and catalyst are added in organic solvent, then are dripped
Methylate chloride carries out condensation reaction, and gained reaction solution is post-treated, obtains pirimiphos-methyl, completes the control to objectionable impurities
System.
The control method of objectionable impurities in above-mentioned pirimiphos-methyl synthesis, it is preferred that the Methochloride is O, O-
Dimethyl thiophosphoryl chloride, 15~25 DEG C of dropping temperature, time for adding is 2~3h, drips continuation condensation reaction 1h.
The control method of objectionable impurities in above-mentioned pirimiphos-methyl synthesis, it is preferred that the catalyst is N, N- diformazans
Base -4-aminopyridine, its consumption is the 0.1%~0.4% of methyl chloride amount of substance.
The control method of objectionable impurities in above-mentioned pirimiphos-methyl synthesis, it is preferred that the organic solvent includes toluene
Or methyl iso-butyl ketone (MIBK), the volume of the organic solvent is 3~5 times of Methochloride volume.
The control method of objectionable impurities in above-mentioned pirimiphos-methyl synthesis, it is preferred that the Methochloride and 2-N,
The mol ratio of N- diethylamino -6- methyl -4- hydroxy pyrimidine metal salts is 1: 1.03~1.1.
The control method of objectionable impurities in above-mentioned pirimiphos-methyl synthesis, it is preferred that the 2-N, N- diethylamino-
6- methyl -4- hydroxy pyrimidines metal salt is 2-N, N- diethylaminos -6- methyl -4- hydroxy pyrimidines sodium salt or 2-N, N- diethyl
Amino -6- methyl -4- hydroxy pyrimidine sylvite.
The control method of objectionable impurities in above-mentioned pirimiphos-methyl synthesis, it is preferred that the 2-N, N- diethylamino-
6- methyl -4- hydroxy pyrimidine metal salts are made by following methods：By 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidines with
Sodium hydroxide or potassium hydroxide react in toluene, filter, and dry, obtain 2-N, N- diethylamino -6- methyl -4- hydroxyls are phonetic
Pyridine metal salt.
The control method of objectionable impurities in above-mentioned pirimiphos-methyl synthesis, it is preferred that 2-N, N- diethylamino -6- first
The mol ratio of base -4- hydroxy pyrimidines and sodium hydroxide or potassium hydroxide is 1: 1.0~1.1.
The control method of objectionable impurities in above-mentioned pirimiphos-methyl synthesis, it is preferred that the post processing includes：Will reaction
Vacuum desolvation after liquid washing, obtains pirimiphos-methyl.
The control method of objectionable impurities in above-mentioned pirimiphos-methyl synthesis, it is preferred that the vacuum of the vacuum desolvation
For -0.098MPa.
Compared with prior art, the advantage of the invention is that：
1st, the present invention due to using Methochloride and 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidines sodium salt or
Sylvite prepares synthesizing methyl Diothyl in non-aqueous organic solvent, therefore methyl thiotep content is very low in product.
2nd, the present invention accelerates main reaction speed due to adding N, N- dimethyl -4-aminopyridine (DMAP) catalyst, drops
Low reaction temperature and product isomery caused by localized clusters is avoided during Methochloride is added dropwise, therefore different first in product
Yl pyrimidines phosphorus content is less than 0.2%.
3rd, the pirimiphos-methyl product purity that the present invention is synthesized is more than 98%, and wherein objectionable impurities methyl thiotep content is small
In 0.06%, different pirimiphos-methyl is less than 0.2%, O, O, S- trimethyls phosphorodithioate, O, O, S- trimethyl D2EHDTPAs
Ester, O, O, O- trimethyl phosphorothioates etc. are respectively less than 0.1%, and this illustrates that all objectionable impurities are limited the quantity concentration far below FAO
Standard.
Embodiment
Below in conjunction with specific preferred embodiment, the invention will be further described, but not thereby limiting the invention
Protection domain.
Embodiment 1：
A kind of control method of objectionable impurities in pirimiphos-methyl synthesis of the invention, its process is as follows：
With addition 93.3g (0.5mol) 2-N, N- in cooling tube, dropping funel, thermometer, the 500mL three-necked flasks of stirring
Diethylamino -6- methyl -4- hydroxy pyrimidines (97%), 300mL toluene and 20.4g (0.50mol) sodium hydroxide (98%), room
Temperature stirring 2h, filtering, filter cake drying obtains 101g white 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sodium salts.
With addition 101g white 2-N, N- diethyls in cooling tube, dropping funel, thermometer, the 1000mL three-necked flasks of stirring
Base amino -6- methyl -4- hydroxy pyrimidines sodium salt, 0.2g DMAP catalyst and 200mL toluene, the lower dropwise addition 80.8g of 20 DEG C of stirrings contain
99%O is measured, O- dimethyl thiophosphoryl chlorides, in being added in 4 hours and continuing to react lh, react and terminate to add the stirring of 200mL water,
Stand split-phase.Oil reservoir adds the stirring of 200mL water, stands split-phase, and oil reservoir precipitation under -0.098MPa obtains 142.1g98.0%
Pirimiphos-methyl (liquid chromatogram external standard), yield 91.3% (in terms of Methochloride).Wherein methyl thiotep content 0.03%,
Different methylpyrimidine phosphorus content 0.13%, O, O, S- trimethyl phosphordithiic acid ester content 0.07%, O, O, the thio phosphorus of S- trimethyls
Acid and esters content 0.05%, O, O, O- trimethyl phosphorothioates 0.03% (gas-chromatography internal standard).
Embodiment 2：
A kind of control method of objectionable impurities in pirimiphos-methyl synthesis of the invention, its process is as follows：
With addition 93.3g (0.5mol) 2-N, N- in cooling tube, dropping funel, thermometer, the 500mL three-necked flasks of stirring
Diethylamino -6- methyl -4- hydroxy pyrimidines (97%), 300mL toluene and 22.4g (0.55mol) sodium hydroxide (98%), room
Temperature stirring 2h, filtering, filter cake drying obtains 103.1g white 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sodium salts.
With addition 103.1g whites 2-N, N- bis- in cooling tube, dropping funel, thermometer, the 1000mL three-necked flasks of stirring
Ethylamino -6- methyl -4- hydroxy pyrimidines sodium salt, 0.2g DMAP catalyst and 300mL toluene, 20 DEG C of stirrings are lower to be added dropwise 78.4g
Content 99%O, O- dimethyl thiophosphoryl chloride, in being added in 3 hours and continuing to react 1h, reaction terminates addition 200mL water and stirred
Mix, stand split-phase.Oil reservoir adds the stirring of 200mL water, stands split-phase, and oil reservoir precipitation under -0.098MPa is obtained
143.3g98.2% pirimiphos-methyls (liquid chromatogram external standard), yield 92.3% (in terms of Methochloride).Wherein methyl sulphur is special
General content 0.02%, different methylpyrimidine phosphorus content 0.18%, O, O, S- trimethyl phosphordithiic acid ester content 0.03%, O, O, S-
Trimethyl phosphorothioate content 0.09%, O, O, O- trimethyl phosphorothioates 0.05% (gas-chromatography internal standard) (gas phase color
Compose internal standard).
Embodiment 3：
A kind of control method of objectionable impurities in pirimiphos-methyl synthesis of the invention, its process is as follows：
With addition 93.3g (0.5mol) 2-N, N- in cooling tube, dropping funel, thermometer, the 500mL three-necked flasks of stirring
Diethylamino -6- methyl -4- hydroxy pyrimidines (97%), 300mL toluene and 32.1g (0.55mol) potassium hydroxide (96%), room
Temperature stirring 2h, filtering, filter cake drying obtains 113.2g white 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sylvite.
With addition 112.2g whites 2-N, N- bis- in cooling tube, dropping funel, thermometer, the 1000mL three-necked flasks of stirring
Ethylamino -6- methyl -4- hydroxy pyrimidines sodium salt, 0.1g DMAP catalyst and 300mL toluene, 15 DEG C of stirrings are lower to be added dropwise 80.8g
Content 99%O, O- dimethyl thiophosphoryl chloride, in being added in 2 hours and continuing to react 1h, reaction terminates addition 200mL water and stirred
Mix, stand split-phase.Oil reservoir adds the stirring of 200mL water, stands split-phase, and oil reservoir precipitation under -0.098MPa is obtained
144.6g98.6% pirimiphos-methyls (liquid chromatogram external standard), yield 93.5% (in terms of Methochloride).Wherein methyl sulphur is special
General content 0.05%, different methylpyrimidine phosphorus content 0.09%, O, O, S- trimethyl phosphordithiic acid ester content 0.03%, O, O, S-
Trimethyl phosphorothioate content 0.06%, O, O, O- trimethyl phosphorothioates 0.06% (gas-chromatography internal standard).
Embodiment 4：
A kind of control method of objectionable impurities in pirimiphos-methyl synthesis of the invention, its process is as follows：
With addition 93.3g (0.50mol) 2-N in cooling tube, dropping funel, thermometer, the 500mL three-necked flasks of stirring,
N- diethylamino -6- methyl -4- hydroxy pyrimidines (97%), 300mL toluene and 29.2g (0.50mol) potassium hydroxide (96%),
2h is stirred at room temperature, filters, filter cake drying obtains 111.0g white 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sylvite.
With addition 111.0g whites 2-N, N- bis- in cooling tube, dropping funel, thermometer, the 1000mL three-necked flasks of stirring
Ethylamino -6- methyl -4- hydroxy pyrimidines sodium salt, 0.1g DMAP catalyst and 200mLMIBK, 25 DEG C of stirrings are lower to be added dropwise 80.8g
Content 99%O, O- dimethyl thiophosphoryl chloride, in being added in 2 hours and continuing to react 1h, reaction terminates addition 200mL water and stirred
Mix, stand split-phase.Oil reservoir adds the stirring of 200mL water, stands split-phase, and oil reservoir precipitation under -0.098MPa is obtained
142.8g98.5% pirimiphos-methyls (liquid chromatogram external standard), yield 95.1% (in terms of Methochloride).Wherein methyl sulphur is special
General content 0.03%, different methylpyrimidine phosphorus content 0.11% (gas-chromatography internal standard).
Embodiment 5：
A kind of control method of objectionable impurities in pirimiphos-methyl synthesis of the invention, its process is as follows：
With addition 93.3g (0.50mol) 2-N in cooling tube, dropping funel, thermometer, the 500mL three-necked flasks of stirring,
N- diethylamino -6- methyl -4- hydroxy pyrimidines (97%), 300mL toluene and 29.8g (0.51mol) potassium hydroxide (96%),
2h is stirred at room temperature, filters, filter cake drying obtains 111.9g white 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sylvite.
With addition 119.0g whites 2-N, N- bis- in cooling tube, dropping funel, thermometer, the 1000mL three-necked flasks of stirring
Ethylamino -6- methyl -4- hydroxy pyrimidines sodium salt, 0.2g DMAP catalyst and 300mL toluene, 15 DEG C of stirrings are lower to be added dropwise 78.4g
Content 99%O, O- dimethyl thiophosphoryl chloride, in being added in 3 hours and continuing to react 1h, reaction terminates addition 200mL water and stirred
Mix, stand split-phase.Oil reservoir adds the stirring of 200mL water, stands split-phase, and oil reservoir precipitation under -0.098MPa is obtained
141.7g98.7% pirimiphos-methyls (liquid chromatogram external standard), yield 91.7% (in terms of Methochloride).Wherein methyl sulphur is special
General content 0.02%, different methylpyrimidine phosphorus content 0.07% (gas-chromatography internal standard).
Embodiment 6：
A kind of control method of objectionable impurities in pirimiphos-methyl synthesis of the invention, its process is as follows：
With addition 93.3g (0.50mol) 2-N in cooling tube, dropping funel, thermometer, the 500mL three-necked flasks of stirring,
N- diethylamino -6- methyl -4- hydroxy pyrimidines (97%), 300mL toluene and 29.8g (0.51mol) potassium hydroxide (96%),
2h is stirred at room temperature, filters, filter cake drying obtains 112.2g white 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sylvite.
With addition 112.2g whites 2-N, N- bis- in cooling tube, dropping funel, thermometer, the 1000mL three-necked flasks of stirring
Ethylamino -6- methyl -4- hydroxy pyrimidines sylvite, 0.1g DMAP catalyst and 300mLMIBK, 20 DEG C of stirrings are lower to be added dropwise 80.8g
Content 99%O, O- dimethyl thiophosphoryl chloride, in being added in 3 hours and continuing to react 1h, reaction terminates addition 200mL water and stirred
Mix, stand split-phase.Oil reservoir adds the stirring of 200mL water, stands split-phase, and oil reservoir precipitation under -0.098MPa is obtained
144.0g98.3% pirimiphos-methyls (liquid chromatogram external standard), yield 92.8% (in terms of Methochloride).Wherein methyl sulphur is special
General content 0.06%, different methylpyrimidine phosphorus content 0.08% (gas-chromatography internal standard).
Embodiment 7：
A kind of control method of objectionable impurities in pirimiphos-methyl synthesis of the invention, its process is as follows：
With addition 93.3g (0.5mol) 2-N, N- in cooling tube, dropping funel, thermometer, the 500mL three-necked flasks of stirring
Diethylamino -6- methyl -4- hydroxy pyrimidines (97%), 300mL toluene and 21.2g (0.52mol) sodium hydroxide (98%), room
Temperature stirring 2h, filtering, filter cake drying obtains 102.5g white 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sodium salts.
With addition 102.5g whites 2-N, N- bis- in cooling tube, dropping funel, thermometer, the 1000mL three-necked flasks of stirring
Ethylamino -6- methyl -4- hydroxy pyrimidines sodium salt, 0.2g DMAP catalyst and 300mLMIBK, 25 DEG C of stirrings are lower to be added dropwise 80.8g
Content 99%O, O- dimethyl thiophosphoryl chloride, in being added in 3 hours and continuing to react 1h, reaction terminates addition 200mL water and stirred
Mix, stand split-phase.Oil reservoir adds the stirring of 200mL water, stands split-phase, and oil reservoir precipitation under -0.098MPa is obtained
142.4g98.5% pirimiphos-methyls (liquid chromatogram external standard), yield 91.9% (in terms of Methochloride).Wherein methyl sulphur is special
General content 0.04%, different methylpyrimidine phosphorus content 0.15% (gas-chromatography internal standard).
Described above is only the preferred embodiment of the present invention, and protection scope of the present invention is not limited merely to above-mentioned implementation
Example.All technical schemes belonged under thinking of the present invention belong to protection scope of the present invention.It is noted that for the art
Those of ordinary skill for, improvements and modifications under the premise without departing from the principles of the invention, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (10)
1. the control method of objectionable impurities, comprises the following steps in a kind of pirimiphos-methyl synthesis：
By 2-N, N- diethylaminos -6- methyl -4- hydroxy pyrimidines metal salt and catalyst are added in organic solvent, then first is added dropwise
Base chloride carries out condensation reaction, and gained reaction solution is post-treated, obtains pirimiphos-methyl, completes the control to objectionable impurities.
2. the control method of objectionable impurities in pirimiphos-methyl synthesis according to claim 1, it is characterised in that the first
Base chloride be O, O- dimethyl thiophosphoryl chlorides, 15~25 DEG C of dropping temperature, time for adding be 2~3h, drip continuation contract
Close reaction 1h.
3. the control method of objectionable impurities in pirimiphos-methyl synthesis according to claim 2, it is characterised in that described to urge
Agent is N, and N- dimethyl -4-aminopyridine, its consumption is the 0.1%~0.4% of methyl chloride amount of substance.
4. the control method of objectionable impurities in pirimiphos-methyl synthesis according to claim 3, it is characterised in that described to have
Machine solvent includes toluene or methyl iso-butyl ketone (MIBK), and the volume of the organic solvent is 3~5 times of Methochloride volume.
5. the control method of objectionable impurities in pirimiphos-methyl synthesis according to claim 4, it is characterised in that the first
The mol ratio of base chloride and 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine metal salts is 1: 1.03~1.1.
6. the control method of objectionable impurities in the pirimiphos-methyl synthesis according to any one of Claims 1 to 4, its feature exists
In the 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidines metal salt is 2-N, N- diethylamino -6- methyl -4- hydroxyls
Yl pyrimidines sodium salt or 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sylvite.
7. the control method of objectionable impurities in pirimiphos-methyl synthesis according to claim 6, it is characterised in that the 2-
N, N- diethylamino -6- methyl -4- hydroxy pyrimidine metal salts are made by following methods：By 2-N, N- diethylamino -6- first
Base -4- hydroxy pyrimidines and sodium hydroxide or potassium hydroxide reacts in toluene, filter, drying, obtain 2-N, and N- diethylaminos -
6- methyl -4- hydroxy pyrimidine metal salts.
8. the control method of objectionable impurities in pirimiphos-methyl synthesis according to claim 7, it is characterised in that 2-N, N-
The mol ratio of diethylamino -6- methyl -4- hydroxy pyrimidines and sodium hydroxide or potassium hydroxide is 1: 1.0~1.1.
9. the control method of objectionable impurities in the pirimiphos-methyl synthesis according to any one of Claims 1 to 4, its feature exists
In the post processing includes：Vacuum desolvation after reaction solution is washed, obtains pirimiphos-methyl.
10. the control method of objectionable impurities in pirimiphos-methyl synthesis according to claim 9, it is characterised in that described
The vacuum of vacuum desolvation is -0.098MPa.
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| CN110684110A (en) * | 2019-09-20 | 2020-01-14 | 北京勤邦生物技术有限公司 | Preparation and application of pirimiphos-methyl monoclonal antibody |
| CN112358501A (en) * | 2020-11-20 | 2021-02-12 | 湖南海利常德农药化工有限公司 | Green synthesis method of pirimiphos-methyl |
| CN114213459A (en) * | 2021-12-16 | 2022-03-22 | 湖南化工研究院有限公司 | Continuous synthesis method of pirimiphos-methyl |
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