CN107011381B - 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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- CN107011381B CN107011381B CN201710290360.3A CN201710290360A CN107011381B CN 107011381 B CN107011381 B CN 107011381B CN 201710290360 A CN201710290360 A CN 201710290360A CN 107011381 B CN107011381 B CN 107011381B
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- methyl
- pirimiphos
- diethylamino
- objectionable impurities
- hydroxy pyrimidine
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- 239000005924 Pirimiphos-methyl Substances 0.000 title claims abstract description 66
- 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 66
- 239000012535 impurity Substances 0.000 title claims abstract description 60
- 238000000034 method Methods 0.000 title claims abstract description 39
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 29
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 29
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 48
- 238000006243 chemical reaction Methods 0.000 claims abstract description 36
- -1 methyl thiotep Chemical compound 0.000 claims abstract description 31
- 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 abstract description 29
- 239000003054 catalyst Substances 0.000 claims abstract description 16
- 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 8
- 238000006482 condensation reaction Methods 0.000 claims abstract description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 57
- 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
- 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
- 238000001556 precipitation Methods 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 7
- 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
- 238000004807 desolvation Methods 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- 229940050176 methyl chloride Drugs 0.000 claims description 2
- NQCPECCCWDWTJJ-UHFFFAOYSA-N 2-diethylamino-6-methylpyrimidin-4(1H)-one Chemical compound CCN(CC)C1=NC(=O)C=C(C)N1 NQCPECCCWDWTJJ-UHFFFAOYSA-N 0.000 claims 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
- NBAUXRCSDWYKRP-UHFFFAOYSA-N dimethyl phosphorochloridothioate Chemical compound COP(Cl)(=O)SC NBAUXRCSDWYKRP-UHFFFAOYSA-N 0.000 description 9
- 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
- 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
- 239000002904 solvent Substances 0.000 description 7
- XWSLYQXUTWUIKM-UHFFFAOYSA-N trimethoxy(sulfanylidene)-$l^{5}-phosphane Chemical compound COP(=S)(OC)OC XWSLYQXUTWUIKM-UHFFFAOYSA-N 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
- 239000003814 drug Substances 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- WTUNGUOZHBRADH-UHFFFAOYSA-N [methoxy(methylsulfanyl)phosphoryl]oxymethane Chemical compound COP(=O)(OC)SC WTUNGUOZHBRADH-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
- 150000002148 esters Chemical class 0.000 description 3
- 239000000575 pesticide Substances 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
- 239000003513 alkali Substances 0.000 description 2
- 238000004458 analytical method Methods 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
- 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
- 238000002360 preparation method Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-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
- 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
- 239000003905 agrochemical Substances 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
- 230000008859 change Effects 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
- BOKOVLFWCAFYHP-UHFFFAOYSA-N dihydroxy-methoxy-sulfanylidene-$l^{5}-phosphane Chemical compound COP(O)(O)=S BOKOVLFWCAFYHP-UHFFFAOYSA-N 0.000 description 1
- ILDHFYGNYDICFB-UHFFFAOYSA-N dimethoxy-methylsulfanyl-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SC ILDHFYGNYDICFB-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229960004979 fampridine Drugs 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
- 231100001231 less toxic Toxicity 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 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
- 238000012805 post-processing Methods 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910001950 potassium oxide Inorganic materials 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 methods of objectionable impurities in a kind of synthesis of pirimiphos-methyl, the following steps are included: by 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine metal salt and catalyst are added in organic solvent, O is added dropwise again, O- dimethyl thiophosphoryl chloride carries out condensation reaction, gained reaction solution is post-treated, obtains pirimiphos-methyl, completes the control of objectionable impurities.The control method of objectionable impurities can be effectively controlled 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 standard.
Description
Technical field
The invention belongs to objectionable impurities in hygienic medication preparation technical field more particularly to a kind of synthesis of pirimiphos-methyl
Control method.
Background technique
Pirimiphos-methyl is less toxic (LD50 2050mg/kg), efficiently (dosage of grain warehousing is 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 in developed country as family
Hygienic medication uses.
Although pirimiphos-methyl, which belongs to low toxic pesticide, to be widely used, FAO is to pirimiphos-methyl raw medicine 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 phosphorothioate, O, O, O- trimethyl phosphorothioate and different pirimiphos-methyl, which has, strictly to be wanted
(control is below 0.5%) is asked, what other were not included in has hypertoxic impurity to be each necessarily less than 0.1% people, animal.Although methyl is phonetic
The main content of pyridine phosphorus raw medicine is greater 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.Since Light absorbing impurty index is excessively harsh, the product of agrochemical enterprise, China production
American-European countries's purchase requirement cannot still be reached at present.
The best industrial method of pirimiphos-methyl is all made of Methochloride and 2-N, N- diethylamino -6- methyl -
Removing solvent is evaporated in vacuo again and obtains product for the condensation of 4- hydroxy pyrimidine after reaction solution washing.Since pirimiphos-methyl has boiling point
The properties such as height, poorly water-soluble, thermal stability poor (being easily decomposed into the different pirimiphos-methyl of objectionable impurities) are brought into and are contracted in primary raw material
The impurity for closing the poorly water-soluble for reacting newly-generated can stay in the product, and leading to objectionable impurities in raw medicine is more than limit standard.Through
Cross analysis, O in above-mentioned objectionable impurities, O, S- trimethyl phosphorodithioate, O, O, S- trimethyl phosphorothioate, O, O, O- tri-
The Methochloride of high-quality can be used (it is required that each both from key intermediate Methochloride in methylphosphorothioate
Impurity content avoids such contaminant overstandard lower than 0.1%)；Reaction, which is not thorough remaining Methochloride, can also pass through change
The feed ratio of raw material realizes strict control；But the impurity such as different pirimiphos-methyl and methyl thiotep generated during the reaction
How to control in lower concentration, never pertinent literature introduction.
ZL200910043946.5 discloses Methochloride and 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine
For raw material, sodium hydroxide is acid binding agent, and toluene and water are solvent, and by the way that hydrolysis inhibitor and catalyst is added, is effectively inhibited
O, the hydrolysis of O- dimethyl thiophosphoryl chloride realize 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, can not be kept away
Exempt to generate the methyl thiotep (two thiopyrophosphate of O, O, O, O- tetramethyl) etc. of people, animal severe toxicity and teratogenesis, first in product
Base thiotep content 0.11%~0.37%, and O, O, O- trimethyl phosphorothioate are all larger than 1%, this two impurity indexs
It is unable to reach FAO standard.
Nie Ping etc. (fine-chemical intermediate, the 2010, the 1st phase) uses Methochloride and 2-N, N- diethylamino -6-
Methyl -4- hydroxy pyrimidine is raw material, and sodium hydroxide is acid binding agent, and toluene is solvent, and sodium sulphate is added as hydrolysis inhibitor, instead
25~35 DEG C of temperature are answered, the pirimiphos-methyl of content 99% is obtained, yield 94% does not control related objectionable impurities.By
Equimolar water is generated in the reaction, hydrolysis inhibitor, which is added, can only reduce but not be avoided that methyl thiotep is formed.
Road sun etc. (Sichuan chemical industry, the 2005, the 6th phase) uses 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, 40~50 DEG C of reaction temperature, obtains content 95%
Pirimiphos-methyl, yield 94% do not control related objectionable impurities.
Zhou Yukun etc. (pesticide, the 2002, the 1st phase) uses Methochloride and 2-N, N- diethylamino -6- methyl -4- hydroxyl
Yl pyrimidines are raw material, and potassium carbonate is acid binding agent, and ethyl acetate is solvent, 45~50 DEG C of reaction temperature, obtain content 85-90%'s
Pirimiphos-methyl, yield 94% do not control related objectionable impurities.
Shen Delong etc. (Guangdong chemical industry, the 2001, the 3rd phase) uses Methochloride and 2-N, N- diethylamino -6- methyl -
4- hydroxy pyrimidine is raw material, and sodium hydroxide is acid binding agent, and room temperature reaction obtains pirimiphos-methyl, and yield 93% does not have 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, 70~75 DEG C of reaction temperature, obtains the first of content 95%
Yl pyrimidines phosphorus, yield 96% do not control related objectionable impurities.
O in current 99% Methochloride industrial goods, O, S- trimethyl phosphorodithioate, O, O, the thio phosphorus of S- trimethyl
Acid esters, O, O, O- trimethyl phosphorothioate etc. can be lower 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 the requirement of FAO
And it is in line with international standards, it is necessary to avoid as far as possible during the reaction generate the objectionable impurities such as methyl thiotep and different pirimiphos-methyl or
It is controlled in the case where defined limitation is horizontal.It is therefore desirable to develop a kind of pirimiphos-methyl that can be effectively controlled objectionable impurities
Synthetic method.
Summary of the invention
The technical problem to be solved by the present invention is to overcome the deficiencies in the prior art, providing has in a kind of pirimiphos-methyl synthesis
The control method of impurity is done harm to, wherein the amount of objectionable impurities methyl thiotep (< 0.06%) and different pirimiphos-methyl (< 0.2%)
Far below FAO limitation concentration standard.
Invention thinking of the invention is the original generated based on the analysis objectionable impurities such as methyl thiotep and different pirimiphos-methyl
Cause, and corresponding means is taken to inhibit its generation:
1. Methochloride generates impurity methyl thiotep (as shown in formula (1)) in water presence: using sodium hydroxide, hydrogen
Potassium oxide, sodium carbonate, potassium carbonate, potassium phosphate etc. and 2-N, in N- diethylamino -6- methyl -4- hydroxy pyrimidine salification process
Not can avoid can generate water, and use water as the generation of the more advantageous impurity methyl thiotep of solvent of above-mentioned inorganic base.
There are above formula reaction generation when inorganic strong alkali and higher reaction temperature, can be accelerated especially in system, it is added neutral
Hydrolysis inhibitor not can avoid the reaction generation.The present invention passes through first by 2-N, and N- diethylamino -6- methyl -4- hydroxyl is phonetic
Pyridine prepares corresponding 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sodium salt or potassium with sodium hydroxide or potassium hydroxide
Salt reacts in the organic solvents such as toluene with Methochloride again after drying (as shown in formula (2)), due to nothing in reaction system
Water or water are few, therefore can be to avoid generation methyl thiotep or the control of its content in extremely low level.
2. (Methochloride is highly acid substance) easily resets that generate impurity different under pirimiphos-methyl is heated or acid condition
Pirimiphos-methyl (as shown in formula (3)), thus take lower reaction temperature and Methochloride is avoided excessively may be used in systems
Effectively to avoid the generation of the different pirimiphos-methyl of impurity.
Applicant has found in early-stage study, although using 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sodium salt
Or sylvite replaces sodium hydroxide or potassium hydroxide acid binding agent that can generate to avoid methyl thiotep, but due to sodium salt or the alkali of sylvite
Property it is low compared with sodium hydroxide and potassium hydroxide, it is also relatively slow with the reaction speed of Methochloride, especially reaction the later period drop
The Methochloride localized clusters of addition system will lead to and generate more different pirimiphos-methyl.Therefore in lower reaction temperature
Degree is lower to guarantee reaction speed, and the catalyst for being conducive to non-homogeneous condensation reaction need to be added in the reaction system.
In order to solve the above technical problems, the invention adopts the following technical scheme:
The control method of objectionable impurities in a kind of synthesis of pirimiphos-methyl, comprising the following steps:
By 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine metal salt and catalyst are added in organic solvent, then drip
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 and continues condensation reaction 1h.
The control method of objectionable impurities in above-mentioned pirimiphos-methyl synthesis, it is preferred that the catalyst is N, N- diformazan
Base -4-aminopyridine, dosage are 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 are 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 molar ratio of N- diethylamino -6- methyl -4- hydroxy pyrimidine metal salt 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 pyrimidine metal salt is 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine 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 salt is made by following methods: by 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine with
Sodium hydroxide or potassium hydroxide react in toluene, filter, dry, obtain 2-N, N- diethylamino -6- methyl -4- hydroxyl is 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 molar ratio of base -4- hydroxy pyrimidine 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: that will react
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 degree of the vacuum desolvation
For -0.098MPa.
Compared with the prior art, the advantages of the present invention are as follows:
1, the present invention due to use Methochloride and 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sodium salt or
Sylvite prepares synthesizing methyl Diothyl in non-aqueous organic solvent, therefore methyl thiotep content is very low in product.
2, the present invention accelerates main reaction speed since N, N- dimethyl -4-aminopyridine (DMAP) catalyst is added, and drops
Low reaction temperature and product isomery caused by localized clusters during Methochloride is added dropwise is avoided, therefore different first in product
Yl pyrimidines phosphorus content is less than 0.2%.
3, the pirimiphos-methyl product purity that the present invention synthesizes is greater 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- trimethyl phosphorodithioate, O, O, S- trimethyl thiophosphoric acid
Ester, O, O, O- trimethyl phosphorothioate etc. are respectively less than 0.1%, this illustrates that all objectionable impurities are far below FAO limitation concentration
Standard.
Specific embodiment
Below in conjunction with specific preferred embodiment, the invention will be further described, but not thereby limiting the invention
Protection scope.
Embodiment 1:
The control method of objectionable impurities, process are as follows in a kind of pirimiphos-methyl synthesis of the invention:
With cooling tube, dropping funel, thermometer, stirring 500mL three-necked flask in be added 93.3g (0.5mol) 2-N, N-
Diethylamino -6- methyl -4- hydroxy pyrimidine (97%), 300mL toluene and 20.4g (0.50mol) sodium hydroxide (98%), room
Temperature stirring 2h, filtering, filter cake dry to obtain 101g white 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sodium salt.
With cooling tube, dropping funel, thermometer, stirring 1000mL three-necked flask in be added 101g white 2-N, N- diethyl
Base amino -6- methyl -4- hydroxy pyrimidine sodium salt, 0.2g DMAP catalyst and 200mL toluene, the lower dropwise addition 80.8g of 20 DEG C of stirrings contain
Measure 99%O, O- dimethyl thiophosphoryl chloride, in being added in 4 hours and the reaction was continued lh, reaction terminate that the stirring of 200mL water is added,
Stand split-phase.The stirring of 200mL water is added in oil reservoir, stands split-phase, and oil reservoir precipitation at -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- trimethyl
Acid and esters content 0.05%, O, O, O- trimethyl phosphorothioate 0.03% (gas-chromatography internal standard).
Embodiment 2:
The control method of objectionable impurities, process are as follows in a kind of pirimiphos-methyl synthesis of the invention:
With cooling tube, dropping funel, thermometer, stirring 500mL three-necked flask in be added 93.3g (0.5mol) 2-N, N-
Diethylamino -6- methyl -4- hydroxy pyrimidine (97%), 300mL toluene and 22.4g (0.55mol) sodium hydroxide (98%), room
Temperature stirring 2h, filtering, filter cake dry to obtain 103.1g white 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sodium salt.
With cooling tube, dropping funel, thermometer, stirring 1000mL three-necked flask in be added 103.1g white 2-N, N- bis-
Ethylamino -6- methyl -4- hydroxy pyrimidine 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 adding in 3 hours and the reaction was continued 1h, reaction, which terminates 200mL water is added, is stirred
It mixes, stands split-phase.The stirring of 200mL water is added in oil reservoir, stands split-phase, and oil reservoir precipitation at -0.098MPa obtains
143.3g98.2% pirimiphos-methyl (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 phosphorothioate 0.05% (gas-chromatography internal standard) (gas phase color
Compose internal standard).
Embodiment 3:
The control method of objectionable impurities, process are as follows in a kind of pirimiphos-methyl synthesis of the invention:
With cooling tube, dropping funel, thermometer, stirring 500mL three-necked flask in be added 93.3g (0.5mol) 2-N, N-
Diethylamino -6- methyl -4- hydroxy pyrimidine (97%), 300mL toluene and 32.1g (0.55mol) potassium hydroxide (96%), room
Temperature stirring 2h, filtering, filter cake dry to obtain 113.2g white 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sylvite.
With cooling tube, dropping funel, thermometer, stirring 1000mL three-necked flask in be added 112.2g white 2-N, N- bis-
Ethylamino -6- methyl -4- hydroxy pyrimidine 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 adding in 2 hours and the reaction was continued 1h, reaction, which terminates 200mL water is added, is stirred
It mixes, stands split-phase.The stirring of 200mL water is added in oil reservoir, stands split-phase, and oil reservoir precipitation at -0.098MPa obtains
144.6g98.6% pirimiphos-methyl (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 phosphorothioate 0.06% (gas-chromatography internal standard).
Embodiment 4:
The control method of objectionable impurities, process are as follows in a kind of pirimiphos-methyl synthesis of the invention:
With cooling tube, dropping funel, thermometer, stirring 500mL three-necked flask in be added 93.3g (0.50mol) 2-N,
N- diethylamino -6- methyl -4- hydroxy pyrimidine (97%), 300mL toluene and 29.2g (0.50mol) potassium hydroxide (96%),
2h is stirred at room temperature, filters, filter cake dries to obtain 111.0g white 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sylvite.
With cooling tube, dropping funel, thermometer, stirring 1000mL three-necked flask in be added 111.0g white 2-N, N- bis-
Ethylamino -6- methyl -4- hydroxy pyrimidine 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 adding in 2 hours and the reaction was continued 1h, reaction, which terminates 200mL water is added, is stirred
It mixes, stands split-phase.The stirring of 200mL water is added in oil reservoir, stands split-phase, and oil reservoir precipitation at -0.098MPa obtains
142.8g98.5% pirimiphos-methyl (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:
The control method of objectionable impurities, process are as follows in a kind of pirimiphos-methyl synthesis of the invention:
With cooling tube, dropping funel, thermometer, stirring 500mL three-necked flask in be added 93.3g (0.50mol) 2-N,
N- diethylamino -6- methyl -4- hydroxy pyrimidine (97%), 300mL toluene and 29.8g (0.51mol) potassium hydroxide (96%),
2h is stirred at room temperature, filters, filter cake dries to obtain 111.9g white 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sylvite.
With cooling tube, dropping funel, thermometer, stirring 1000mL three-necked flask in be added 119.0g white 2-N, N- bis-
Ethylamino -6- methyl -4- hydroxy pyrimidine 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 adding in 3 hours and the reaction was continued 1h, reaction, which terminates 200mL water is added, is stirred
It mixes, stands split-phase.The stirring of 200mL water is added in oil reservoir, stands split-phase, and oil reservoir precipitation at -0.098MPa obtains
141.7g98.7% pirimiphos-methyl (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:
The control method of objectionable impurities, process are as follows in a kind of pirimiphos-methyl synthesis of the invention:
With cooling tube, dropping funel, thermometer, stirring 500mL three-necked flask in be added 93.3g (0.50mol) 2-N,
N- diethylamino -6- methyl -4- hydroxy pyrimidine (97%), 300mL toluene and 29.8g (0.51mol) potassium hydroxide (96%),
2h is stirred at room temperature, filters, filter cake dries to obtain 112.2g white 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sylvite.
With cooling tube, dropping funel, thermometer, stirring 1000mL three-necked flask in be added 112.2g white 2-N, N- bis-
Ethylamino -6- methyl -4- hydroxy pyrimidine 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 adding in 3 hours and the reaction was continued 1h, reaction, which terminates 200mL water is added, is stirred
It mixes, stands split-phase.The stirring of 200mL water is added in oil reservoir, stands split-phase, and oil reservoir precipitation at -0.098MPa obtains
144.0g98.3% pirimiphos-methyl (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:
The control method of objectionable impurities, process are as follows in a kind of pirimiphos-methyl synthesis of the invention:
With cooling tube, dropping funel, thermometer, stirring 500mL three-necked flask in be added 93.3g (0.5mol) 2-N, N-
Diethylamino -6- methyl -4- hydroxy pyrimidine (97%), 300mL toluene and 21.2g (0.52mol) sodium hydroxide (98%), room
Temperature stirring 2h, filtering, filter cake dry to obtain 102.5g white 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sodium salt.
With cooling tube, dropping funel, thermometer, stirring 1000mL three-necked flask in be added 102.5g white 2-N, N- bis-
Ethylamino -6- methyl -4- hydroxy pyrimidine 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 adding in 3 hours and the reaction was continued 1h, reaction, which terminates 200mL water is added, is stirred
It mixes, stands split-phase.The stirring of 200mL water is added in oil reservoir, stands split-phase, and oil reservoir precipitation at -0.098MPa obtains
142.4g98.5% pirimiphos-methyl (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).
The above is only a preferred embodiment of the present invention, protection scope of the present invention is not limited merely to above-mentioned implementation
Example.All technical solutions belonged under thinking of the present invention all belong to the scope of protection of the present invention.It is noted that for the art
Those of ordinary skill for, improvements and modifications without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (5)
1. the control method of objectionable impurities in a kind of pirimiphos-methyl synthesis, comprising the following steps:
By 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine 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；
The Methochloride is O, and O- dimethyl thiophosphoryl chloride, 15~25 DEG C of dropping temperature, time for adding is 2~3h, is dripped
Continue condensation reaction 1h；The catalyst is N, and N- dimethyl -4-aminopyridine, dosage is the 0.1% of methyl chloride amount of substance
~0.4%；The organic solvent includes toluene or methyl iso-butyl ketone (MIBK), and the volume of the organic solvent is Methochloride volume
3~5 times；The molar ratio of the Methochloride and 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine metal salt are 1:
1.03~1.1；The 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine metal salt are made by following methods: by 2-N, N-
Diethylamino -6- methyl -4- hydroxy pyrimidine reacts in toluene with sodium hydroxide or potassium hydroxide, filters, dry, obtains 2-
N, N- diethylamino -6- methyl -4- hydroxy pyrimidine metal salt.
2. the control method of objectionable impurities in pirimiphos-methyl synthesis according to claim 1, which is characterized in that the 2-
N, N- diethylamino -6- methyl -4- hydroxy pyrimidine metal salt are 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sodium
Salt or 2-N, N- diethylamino -6- methyl -4- hydroxy pyrimidine sylvite.
3. the control method of objectionable impurities in pirimiphos-methyl synthesis according to claim 1, which is characterized in that 2-N, N-
The molar ratio of diethylamino -6- methyl -4- hydroxy pyrimidine and sodium hydroxide or potassium hydroxide is 1:1.0~1.1.
4. the control method of objectionable impurities in pirimiphos-methyl synthesis according to claim 1, which is characterized in that after described
Processing includes: vacuum desolvation after washing reaction solution, obtains pirimiphos-methyl.
5. the control method of objectionable impurities in pirimiphos-methyl synthesis according to claim 4, which is characterized in that described true
The vacuum degree of empty precipitation is -0.098MPa.
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