CN108047024A - A kind of synthetic method of halogenated malonate and halogenated malonic acid - Google Patents
A kind of synthetic method of halogenated malonate and halogenated malonic acid Download PDFInfo
- Publication number
- CN108047024A CN108047024A CN201711322906.5A CN201711322906A CN108047024A CN 108047024 A CN108047024 A CN 108047024A CN 201711322906 A CN201711322906 A CN 201711322906A CN 108047024 A CN108047024 A CN 108047024A
- Authority
- CN
- China
- Prior art keywords
- acid
- halogenated
- malonate
- iii
- synthetic method
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical class OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 150000002690 malonic acid derivatives Chemical class 0.000 title claims abstract description 21
- 238000010189 synthetic method Methods 0.000 title claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims description 57
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 33
- -1 II Chemical class 0.000 claims description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 12
- 239000003513 alkali Substances 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- 235000019441 ethanol Nutrition 0.000 claims description 9
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims description 8
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 8
- 229910017604 nitric acid Inorganic materials 0.000 claims description 8
- 239000003456 ion exchange resin Substances 0.000 claims description 7
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 5
- 229910052751 metal Inorganic materials 0.000 claims description 5
- 239000002184 metal Substances 0.000 claims description 5
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 4
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 claims description 4
- 229910001863 barium hydroxide Inorganic materials 0.000 claims description 4
- 239000005711 Benzoic acid Substances 0.000 claims description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 3
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 3
- 235000010233 benzoic acid Nutrition 0.000 claims description 3
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 3
- 239000000920 calcium hydroxide Substances 0.000 claims description 3
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 3
- 229940071870 hydroiodic acid Drugs 0.000 claims description 3
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 3
- 239000000347 magnesium hydroxide Substances 0.000 claims description 3
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 3
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 229910052723 transition metal Inorganic materials 0.000 claims description 3
- 150000003624 transition metals Chemical class 0.000 claims description 3
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 229910052738 indium Inorganic materials 0.000 claims 1
- UUCCCPNEFXQJEL-UHFFFAOYSA-L strontium dihydroxide Chemical compound [OH-].[OH-].[Sr+2] UUCCCPNEFXQJEL-UHFFFAOYSA-L 0.000 claims 1
- 229910001866 strontium hydroxide Inorganic materials 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 9
- 238000000034 method Methods 0.000 abstract description 9
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical class CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 abstract description 4
- 239000007858 starting material Substances 0.000 abstract 1
- 238000006467 substitution reaction Methods 0.000 abstract 1
- RBCXEDQEZDUMHD-UHFFFAOYSA-N 2-fluoropropanedioic acid Chemical compound OC(=O)C(F)C(O)=O RBCXEDQEZDUMHD-UHFFFAOYSA-N 0.000 description 48
- 239000007787 solid Substances 0.000 description 25
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 22
- 229910052708 sodium Inorganic materials 0.000 description 22
- 239000011734 sodium Substances 0.000 description 22
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 13
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 11
- 239000011775 sodium fluoride Substances 0.000 description 8
- 235000013024 sodium fluoride Nutrition 0.000 description 8
- VBZOUUJVGADJBK-UHFFFAOYSA-N 2-bromopropanedioic acid Chemical compound OC(=O)C(Br)C(O)=O VBZOUUJVGADJBK-UHFFFAOYSA-N 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- AFXWHCJMTLWFKF-UHFFFAOYSA-N 2-chloropropanedioic acid Chemical compound OC(=O)C(Cl)C(O)=O AFXWHCJMTLWFKF-UHFFFAOYSA-N 0.000 description 4
- VEWFSLPWATWECM-UHFFFAOYSA-N BrC(C(=O)O)C(=O)O.[Na] Chemical compound BrC(C(=O)O)C(=O)O.[Na] VEWFSLPWATWECM-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- WUBKQTYVIQWUHP-UHFFFAOYSA-N [Na].C(=O)(O)C(C(=O)O)Cl Chemical compound [Na].C(=O)(O)C(C(=O)O)Cl WUBKQTYVIQWUHP-UHFFFAOYSA-N 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 206010054949 Metaplasia Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 208000012839 conversion disease Diseases 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- 230000015689 metaplastic ossification Effects 0.000 description 2
- 230000005311 nuclear magnetism Effects 0.000 description 2
- 238000012805 post-processing Methods 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- JMRIJKGIVGYIAD-UHFFFAOYSA-N 2,3,3-trifluoroprop-1-ene Chemical compound FC(F)C(F)=C JMRIJKGIVGYIAD-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- HZPRIJSAGJQRGU-UHFFFAOYSA-N [Cl].OS(Cl)(=O)=O Chemical compound [Cl].OS(Cl)(=O)=O HZPRIJSAGJQRGU-UHFFFAOYSA-N 0.000 description 1
- WJEIYVAPNMUNIU-UHFFFAOYSA-N [Na].OC(O)=O Chemical compound [Na].OC(O)=O WJEIYVAPNMUNIU-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 229910000287 alkaline earth metal oxide Inorganic materials 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- OYLGJCQECKOTOL-UHFFFAOYSA-L barium fluoride Chemical compound [F-].[F-].[Ba+2] OYLGJCQECKOTOL-UHFFFAOYSA-L 0.000 description 1
- 229910001632 barium fluoride Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000011964 heteropoly acid Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052755 nonmetal Inorganic materials 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/093—Preparation of carboxylic acids or their salts, halides or anhydrides by hydrolysis of —CX3 groups, X being halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/02—Preparation of carboxylic acids or their salts, halides or anhydrides from salts of carboxylic acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to technical field of organic chemistry, disclose a kind of halogenated malonate（Ⅱ）And halogenated malonic acid（Ⅲ）Synthetic method.This method withN,NTwo 2,3,3,3 4 halogenated propionamides of substitution（Ⅰ）For starting material, halogenated malonate is obtained in the presence of a base（Ⅱ）And halogenated malonic acid（Ⅲ）.Applied widely, mild condition of the invention, it is of low cost, it is suitable for industrialized production.
Description
Technical field
The invention belongs to technical field of organic chemistry, and in particular to a kind of halogenated malonate (II) and halogenated malonic acid (III)
Synthetic method.
Background technology
Halogenated malonate and halogenated malonic acid such as fluoromalonic acid sodium, fluoromalonic acid, chloromalonic acid sodium, chloro third
Diacid, bromomalonic acid sodium, bromomalonic acid etc. are a series of important organic synthesis intermediates, in pesticide, medicine, new material
Field has a wide range of applications.
Conrad etc. (Chemische Berichte, 1902,35,1814) is reported using malonic acid as raw material chlorosulfuric acid chlorine
In generation, prepares the route of chloromalonic acid.The route serious three wastes, yield is low, and labor protection requirement is high, is not suitable for industrialized production.
Lazerte etc. (Journal of the American Chemical Society, 1956,78,5639) report one with
2,3,3- trifluoro propene nitriles are raw material, and the route of fluoromalonic acid is prepared through sulphuric acid hydrolysis, although the route reaction condition is mild,
It is easy to operate, but expensive raw material price should not obtain and severe toxicity, without industrial value.Alba Francesca D etc.
(Journal of the Chemical Society,Faraday Transactions 1:Physical Chemistry in
Condensed Phases, 1983,79,39) one is reported using malonic acid as raw material, prepare bromomalonic acid through bromine bromo
Route.The pollution problem for not only having great security risk using bromine and bringing is also extremely serious.As country is by bromine
Element is classified as controlled drug, and the transport and use of bromine are very restricted, therefore the route applications also have in industrialized production
Many insurmountable drawbacks.
The content of the invention
Goal of the invention：For the deficiencies in the prior art, the object of the present invention is to provide one kind to be suitble to industrial metaplasia
The halogenated malonate (II) of production and the synthetic method of halogenated malonic acid (III), this method mild condition, reaction conversion ratio are high, production
Quality is high, sources of initial raw materials is extensive, and post processing is simple and easy to do, the halogenated malonate (II) and halogen produced using this method
There is the very strong market competitiveness for malonic acid (III).
Technical solution：In order to realize foregoing invention purpose, the technical solution adopted by the present invention is：
A kind of halogenated malonate (II) and the synthetic method of halogenated malonic acid (III) exchange tree in alkali or strong basic ion
In the presence of fat, N, N- bis- substitutes -2,3,3,3- tetra- halogenated propionamides (I) in a solvent or solvent-free system reaction, obtains halogen
For malonate (II)；Halogenated malonate (II) is acidified again to obtain halogenated malonic acid (III)；Reaction equation is as follows：
Wherein, R1And R2For identical or different C1-C20Alkyl；X is F, Cl, Br；The metal of the alkali for alkali metal,
Alkaline-earth metal and transition metal.
The R1And R2It is identical, it is methyl, ethyl or isopropyl.
The solvent is C1-C20Alkyl carboxylic acid class, C1-C10Amides, C1-C10Ethers, water, C1-C10Alcohols it is single
The arbitrary proportion of solvent or these solvents mixes.
The solvent is water, methanol, ethyl alcohol.
The alkali is lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide, magnesium hydroxide, carbonic acid
Sodium, potassium carbonate.
Acidifying acid used is sulfuric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, hydrofluoric acid, nitric acid, phosphoric acid, benzoic acid, acetic acid, benzene
Sulfonic acid, methanesulfonic acid.Acidifying can also be reacted with strong-acid ion exchange resin.
Reaction temperature is 20-200 DEG C, is preferably 50-130 DEG C.
The present processes, solvent be C1-C20 alkyl carboxylic acid classes, C1-C10 amides, C1-C10 ethers, water, C1-C10
The arbitrary proportion mixed solvent of alcohols single solvent or these solvents；It is preferred that water, methanol, ethyl alcohol；Reaction or solvent-free body
System.
The present processes, alkali can be selected from alkali metal oxide, alkali metal hydroxide, alkali carbonate and carbon
Sour hydrogen salt, alkaline earth oxide, alkaline earth metal hydroxide, alkaline earth metal carbonate and bicarbonate, transiting metal oxidation
Object, transition metal hydroxide, alkoxy or aralkoxy metal base, alkyl or aralkyl metal base and these alkali it is molten
Liquid.It is preferred that lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide, magnesium hydroxide, sodium carbonate, potassium carbonate, with
And the mixture of the arbitrary proportion of these alkali.
The present processes, acid is selected from heteropoly acid, solid super-strong acid, the corresponding oxyacid of various metal oxides, hydrogen halogen
The corresponding oxyacid of sour, various nonmetal oxides, alkyl acid, aralkyl acid, alkyl sulfonic acid or aryl sulfonic acid, preferably sulfuric acid,
Hydrochloric acid, hydrobromic acid, hydroiodic acid, hydrofluoric acid, nitric acid, phosphoric acid, benzoic acid, acetic acid, benzene sulfonic acid, methanesulfonic acid.
Advantageous effect：Compared with prior art, the conjunction of halogenated malonate (II) and halogenated malonic acid (III) of the invention
Into method, mild condition, reaction conversion ratio are high, product quality is high, sources of initial raw materials is extensive, and post processing is simple and easy to do, use
The halogenated malonate (II) and halogenated malonic acid (III) of this method production have the very strong market competitiveness, are suitble to industry metaplasia
Production.This method is applied widely, available for production fluoromalonic acid sodium, fluoromalonic acid potassium, fluoromalonic acid lithium, fluoro third
Diacid, chloromalonic acid sodium, chloromalonic acid potassium, chloromalonic acid lithium, chloromalonic acid, bromomalonic acid sodium, bromo the third two
A series of products such as sour potassium, bromomalonic acid lithium, bromomalonic acid.Substitute four halogenated propionyl amine bases of -2,3,3,3- for N, N- bis-
Property hydrolysis prepares halogenated malonic acid and halogenated malonate to provide a reaction condition mild, easy to operate, selectively excellent
Suitable industrialized production synthetic route, the prices of raw materials of the route are cheap, derive from a wealth of sources, have good practicability.
Description of the drawings
Fig. 1 is fluoromalonic acid sodium through nuclear-magnetism testing result figure.
Specific embodiment
This patent is further specifically described below by embodiment, but is not limited to these embodiments.
Embodiment 1：The preparation of chloromalonic acid sodium and chloromalonic acid
By N, N- dimethyl -2,3,3,3- tetrachloros propionamides (10kg), sodium hydroxide (20kg), water (200kg) add in anti-
Kettle is answered, when 50 DEG C of reactions 10 are small, dilute hydrochloric acid absorbs dimethylamine gas in reaction process, and reaction is finished, and filtration from sodium chloride is remaining
Object continues distillation and obtains chloromalonic acid sodium solid 7.33kg, purity 99%.The acidifying of solid hydrochloric acid can obtain chloromalonic acid
5.56kg。
Embodiment 2：The preparation of fluoromalonic acid sodium and fluoromalonic acid
By N, four fluoroalanines (10kg) of N- dimethyl -2,3,3,3-, sodium hydroxide (19kg), water (170kg) add in anti-
Kettle is answered, when 50 DEG C of reactions 10 are small, dilute hydrochloric acid absorbs dimethylamine gas in reaction process, and reaction is finished, and is filtered to remove sodium fluoride, remaining
Object continues distillation and obtains fluoromalonic acid sodium solid 9.2kg, purity 99%.The acidifying of solid hydrofluoric acid can obtain fluoromalonic acid
6.77kg。
Embodiment 3：The preparation of bromomalonic acid sodium and bromomalonic acid
By N, N- diethyl -2,3,3,3- tetrabromos propionamides (10kg), potassium hydroxide (22kg), water (170kg) add in anti-
Kettle is answered, when 50 DEG C of reactions 10 are small, diethylamine is recycled in reaction process, reaction is finished, and is filtered to remove potassium bromide, residue continues to distill
Obtain bromomalonic acid potassium solid 5.65kg, purity 99%.The acidifying of solid hydrobromic acid can obtain bromomalonic acid 4.00kg.
Embodiment 4：The preparation of fluoromalonic acid sodium and fluoromalonic acid
By N, four fluoroalanines (10kg) of N- diethyl -2,3,3,3-, sodium hydroxide (19.5kg), water (190kg) add in
Reaction kettle when 50 DEG C of reactions 10 are small, recycles diethylamine in reaction process, reaction is finished, and is filtered to remove sodium fluoride, residue continues to steam
It evaporates to obtain fluoromalonic acid sodium solid 8.1kg, purity 99%.The acidifying of solid nitric acid can obtain fluoromalonic acid 5.9kg.
Fluoromalonic acid sodium is detected through nuclear-magnetism, as shown in Figure 1,1H-NMR(D2O, 400MHz)：δ=5.0 (d, 1H, J=
52Hz), with document [Sun, Xiao-Guang, Journal of Materials Chemistry A: Materials for
Energy and Sustainability, 2014,20,7606；US 20140113202] report that data are consistent.)
Embodiment 5：The preparation of bromomalonic acid sodium and bromomalonic acid
By N, N- diethyl -2,3,3,3- tetrabromos propionamides (10kg), lithium hydroxide (17kg), water (170kg) add in anti-
Kettle is answered, when 60 DEG C of reactions 10 are small, diethylamine is recycled in reaction process, reaction is finished, and is filtered to remove lithium bromide, residue continues to distill
Obtain bromomalonic acid lithium solid 4.25kg, purity 99%.Solid is acidified after being dissolved in water with 732 strong-acid ion exchange resins,
Ion exchange resin is filtered off, concentration can obtain bromomalonic acid 3.96kg.
Embodiment 6：The preparation of fluoromalonic acid sodium and fluoromalonic acid
By N, four fluoroalanines (10kg) of N- diethyl -2,3,3,3-, 717 strong basic ion exchange resins (190kg),
Water (190kg) adds in reaction kettle, and when 50 DEG C of reactions 10 are small, diethylamine is recycled in reaction process, and reaction is finished, and ion is separated through sieve
Exchanger resin, ion exchange resin are eluted through hydrochloric acid, can obtain fluoromalonic acid 4.0kg.
Embodiment 7：The preparation of fluoromalonic acid sodium and fluoromalonic acid
By N, four fluoroalanines (10kg) of N- diethyl -2,3,3,3-, sodium hydroxide (19.5kg), water (190kg), ethyl alcohol
(10Kg) adds in reaction kettle, when 50 DEG C of reactions 10 are small, diethylamine is recycled in reaction process, reaction is finished, and is filtered to remove sodium fluoride, is remained
Excess continues second alcohol and water is distilled off to obtain fluoromalonic acid sodium solid 7.6kg, purity 99%.The acidifying of solid nitric acid can obtain
Fluoromalonic acid 5.5kg.
Embodiment 8：The preparation of fluoromalonic acid sodium and fluoromalonic acid
By N, four fluoroalanines (10kg) of N- diethyl -2,3,3,3-, barium hydroxide (41kg), water (190kg), ethyl alcohol
(10Kg) adds in reaction kettle, when 50 DEG C of reactions 10 are small, diethylamine is recycled in reaction process, reaction is finished, and is filtered to remove barium fluoride, is remained
Excess continues second alcohol and water is distilled off to obtain fluoromalonic acid barium solid 12.1kg, purity 99%.The acidifying of solid sulfuric acid can
Obtain fluoromalonic acid 5.6kg.
Embodiment 9：The preparation of fluoromalonic acid sodium and fluoromalonic acid
By N, four fluoroalanines (10kg) of N- diethyl -2,3,3,3-, sodium hydroxide (19.5kg), water (190kg) add in
Reaction kettle when 200 DEG C of reactions 3 are small, recycles diethylamine in reaction process, reaction is finished, and is filtered to remove sodium fluoride, residue continues to steam
It evaporates to obtain fluoromalonic acid sodium solid 0.1kg, purity 99%.The acidifying of solid nitric acid can obtain fluoromalonic acid 0.06kg.
Embodiment 10：The preparation of fluoromalonic acid sodium and fluoromalonic acid
By N, four fluoroalanines (10kg) of N- diethyl -2,3,3,3-, sodium hydroxide (19.5kg), water (190kg) add in
Reaction kettle when 130 DEG C of reactions 3 are small, recycles diethylamine in reaction process, reaction is finished, and is filtered to remove sodium fluoride, residue continues to steam
It evaporates to obtain fluoromalonic acid sodium solid 8.1kg, purity 99%.The acidifying of solid sulfuric acid can obtain fluoromalonic acid 5.9kg.
Embodiment 11：The preparation of fluoromalonic acid sodium and fluoromalonic acid
By N, four fluoroalanines (10kg) of N- diethyl -2,3,3,3-, sodium hydroxide (9.7kg), potassium hydroxide
(13.6kg), water (190kg) add in reaction kettle, when 130 DEG C of reactions 3 are small, diethylamine are recycled in reaction process, reaction is finished, filtering
Sodium fluoride and potassium fluoride are removed, residue continues distillation and obtains fluoromalonic acid sodium and fluoromalonic acid potassium solid 8.9kg, purity
99%.The acidifying of solid sulfuric acid can obtain fluoromalonic acid 5.91kg.
Embodiment 12：The preparation of fluoromalonic acid sodium and fluoromalonic acid
By N, four fluoroalanines (10kg) of N- diethyl -2,3,3,3-, sodium hydroxide (19.5kg), water (190kg) add in
Reaction kettle when 20 DEG C of reactions 30 are small, recycles diethylamine in reaction process, reaction is finished, and is filtered to remove sodium fluoride, residue continues to steam
It evaporates to obtain fluoromalonic acid sodium solid 0.01kg, purity 99%.The acidifying of solid nitric acid can obtain fluoromalonic acid 0.007kg.
Embodiment 13：The preparation of fluoromalonic acid sodium and fluoromalonic acid
By N, four fluoroalanines (10kg) of N- diethyl -2,3,3,3-, sodium carbonate (25kg), water (190kg) add in reaction
Kettle when 130 DEG C of reactions 30 are small, recycles diethylamine in reaction process, reaction is finished, and is filtered to remove sodium fluoride, residue continues to distill
Obtain fluoromalonic acid sodium solid 0.5kg, purity 99%.The acidifying of solid nitric acid can obtain fluoromalonic acid 0.3kg.
Claims (9)
1. a kind of halogenated malonate (II) and the synthetic method of halogenated malonic acid (III), which is characterized in that in alkali or strong basicity
In the presence of ion exchange resin, N, N- bis- substitutes -2,3,3,3- tetra- halogenated propionamides (I) in a solvent or solvent-free system is anti-
Should, obtain halogenated malonate (II)；Halogenated malonate (II) is acidified again to obtain halogenated malonic acid (III)；Reaction equation is such as
Under：
Wherein, R1And R2For identical or different C1-C20Alkyl；X is F, Cl, Br；The metal of the alkali is alkali metal, alkaline earth
Metal and transition metal.
2. halogenated malonate (II) according to claim 1 and the synthetic method of halogenated malonic acid (III), feature exist
In the R1And R2It is identical, it is methyl, ethyl or isopropyl.
3. halogenated malonate (II) according to claim 1 and the synthetic method of halogenated malonic acid (III), feature exist
In the solvent is C1-C20Alkyl carboxylic acid class, C1-C10Amides, C1-C10Ethers, water, C1-C10The single solvent of alcohols or
The arbitrary proportion mixing of these solvents.
4. the synthetic method of the halogenated malonate (II) and halogenated malonic acid (III) according to claim 1 or 3, feature
It is, the solvent is water, methanol, ethyl alcohol.
5. halogenated malonate (II) according to claim 1 and the synthetic method of halogenated malonic acid (III), feature exist
In, the alkali be lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide, strontium hydroxide, magnesium hydroxide,
Sodium carbonate, potassium carbonate.
6. halogenated malonate (II) according to claim 1 and the synthetic method of halogenated malonic acid (III), feature exist
In, be acidified acid used for sulfuric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, hydrofluoric acid, nitric acid, phosphoric acid, benzoic acid, acetic acid, benzene sulfonic acid,
Methanesulfonic acid.
7. halogenated malonate (II) according to claim 1 and the synthetic method of halogenated malonic acid (III), feature exist
In acidifying is reacted with strong-acid ion exchange resin.
8. halogenated malonate (II) according to claim 1 and the synthetic method of halogenated malonic acid (III), feature exist
In reaction temperature is 20-200 DEG C.
9. the synthetic method of the halogenated malonate (II) and halogenated malonic acid (III) according to claim 1 or 8, feature
It is, reaction temperature is 50-130 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311339761.5A CN117402053A (en) | 2017-12-08 | 2017-12-12 | Synthesis method of halogenated malonic acid |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711298701 | 2017-12-08 | ||
| CN2017112987018 | 2017-12-08 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311339761.5A Division CN117402053A (en) | 2017-12-08 | 2017-12-12 | Synthesis method of halogenated malonic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108047024A true CN108047024A (en) | 2018-05-18 |
Family
ID=62132015
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711322906.5A Pending CN108047024A (en) | 2017-12-08 | 2017-12-12 | A kind of synthetic method of halogenated malonate and halogenated malonic acid |
| CN202311339761.5A Pending CN117402053A (en) | 2017-12-08 | 2017-12-12 | Synthesis method of halogenated malonic acid |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311339761.5A Pending CN117402053A (en) | 2017-12-08 | 2017-12-12 | Synthesis method of halogenated malonic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (2) | CN108047024A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114702401A (en) * | 2022-06-06 | 2022-07-05 | 山东国邦药业有限公司 | Method for treating florfenicol byproduct N, N-diethyl-2, 3,3, 3-tetrafluoro propionamide |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103508875A (en) * | 2012-06-25 | 2014-01-15 | 赵磊 | 2,3,3,3-tetrafluoro propionic acid (I) synthesis method |
| US20140113202A1 (en) * | 2012-10-22 | 2014-04-24 | Ut-Battelle, Llc | Electrolyte compositions for lithium ion batteries |
-
2017
- 2017-12-12 CN CN201711322906.5A patent/CN108047024A/en active Pending
- 2017-12-12 CN CN202311339761.5A patent/CN117402053A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103508875A (en) * | 2012-06-25 | 2014-01-15 | 赵磊 | 2,3,3,3-tetrafluoro propionic acid (I) synthesis method |
| US20140113202A1 (en) * | 2012-10-22 | 2014-04-24 | Ut-Battelle, Llc | Electrolyte compositions for lithium ion batteries |
Non-Patent Citations (1)
| Title |
|---|
| 戴行义等: "《有机氟化合物的化学》", 30 April 1965, 上海科学技术出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114702401A (en) * | 2022-06-06 | 2022-07-05 | 山东国邦药业有限公司 | Method for treating florfenicol byproduct N, N-diethyl-2, 3,3, 3-tetrafluoro propionamide |
| CN114702401B (en) * | 2022-06-06 | 2022-08-23 | 山东国邦药业有限公司 | Method for treating florfenicol byproduct N, N-diethyl-2, 3,3, 3-tetrafluoro propionamide |
Also Published As
| Publication number | Publication date |
|---|---|
| CN117402053A (en) | 2024-01-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BRPI0714571A2 (en) | process for the production of a compound, and, | |
| CN104844412B (en) | A kind of preparation method of 1,2,4-trifluoro-benzene | |
| CN109293488A (en) | A kind of preparation method of 5-chloro-1-indanone | |
| CN108329211A (en) | The preparation method of 5- chloro-2-nitroanilines | |
| CN113651710A (en) | Preparation method of 3, 5-substituted-4-amino trifluoro acetophenone and its derivative | |
| CN104803839B (en) | A kind of method preparing trifluoroacetic anhydride | |
| CN108047024A (en) | A kind of synthetic method of halogenated malonate and halogenated malonic acid | |
| CN104591959B (en) | A kind of preparation method of stilbene compound | |
| CN103242190B (en) | Synthetic method of propyzamide | |
| JP5782331B2 (en) | Method for producing imidoyl chloride compound and method for producing various compounds using the same | |
| CN106748796B (en) | The method for preparing the fluoro- 2,4- dinitrobenzene of 1,5- bis- | |
| CN110938043A (en) | Parecoxib sodium genotoxic impurity and preparation method thereof | |
| CN106243009B (en) | A kind of preparation method of the bromo- N-phenylmaleimides of 3- n-butylamine-baseds -4- | |
| CN106478422B (en) | A kind of preparation method of paranitrophenylacetic acid | |
| CN112409169B (en) | Method for preparing polyfluoroaromatic hydrocarbon | |
| JPS5925779B2 (en) | Isomerization method for stereoisomeric alicyclic diamines | |
| CN105418391B (en) | A kind of preparation method of p-trifluoromethyl benzaldehyde | |
| CN105732429A (en) | Pentafluorobenzonitrile production method | |
| CN101323578A (en) | Synthetic method of p-amino | |
| CN109912423A (en) | A kind of green synthesis process of 3,5-dinitro-4-methylbenzoic acid | |
| CN104829492A (en) | Preparation method of trans-N-Boc-1,3-cyclobutanediamine | |
| CN117964490B (en) | A method for preparing trifluoromethyl aromatic compounds | |
| WO2017195619A1 (en) | Method for producing nitrobenzene compound | |
| CN100389104C (en) | The preparation method of 2,6-dichloroaniline | |
| CN101935294A (en) | Recovery and Utilization of Two Main By-products in C Acid Production |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180518 |
|
| RJ01 | Rejection of invention patent application after publication |