CN109232451A - A method of preparing benzene sulphur azoles - Google Patents
A method of preparing benzene sulphur azoles Download PDFInfo
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- CN109232451A CN109232451A CN201811265943.1A CN201811265943A CN109232451A CN 109232451 A CN109232451 A CN 109232451A CN 201811265943 A CN201811265943 A CN 201811265943A CN 109232451 A CN109232451 A CN 109232451A
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- aqueous solution
- benzene sulphur
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- CQSQCXPIPHZLQE-UHFFFAOYSA-N N1C=CC=C1.C1=CC=CC=C1.[S] Chemical class N1C=CC=C1.C1=CC=CC=C1.[S] CQSQCXPIPHZLQE-UHFFFAOYSA-N 0.000 title claims abstract description 42
- 238000000034 method Methods 0.000 title claims abstract description 34
- 238000006243 chemical reaction Methods 0.000 claims abstract description 99
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 53
- 239000000463 material Substances 0.000 claims abstract description 48
- 239000000243 solution Substances 0.000 claims abstract description 40
- 239000007787 solid Substances 0.000 claims abstract description 33
- 239000007864 aqueous solution Substances 0.000 claims abstract description 30
- 239000012043 crude product Substances 0.000 claims abstract description 21
- JDEJGVSZUIJWBM-UHFFFAOYSA-N n,n,2-trimethylaniline Chemical compound CN(C)C1=CC=CC=C1C JDEJGVSZUIJWBM-UHFFFAOYSA-N 0.000 claims abstract description 19
- 150000003852 triazoles Chemical class 0.000 claims abstract description 18
- 150000003863 ammonium salts Chemical class 0.000 claims abstract description 17
- 238000002156 mixing Methods 0.000 claims abstract description 17
- 239000012266 salt solution Substances 0.000 claims abstract description 17
- 239000002253 acid Substances 0.000 claims abstract description 14
- 239000002904 solvent Substances 0.000 claims abstract description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 150000001335 aliphatic alkanes Chemical class 0.000 claims abstract description 8
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims abstract description 7
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 6
- 238000013517 stratification Methods 0.000 claims abstract description 6
- 150000007529 inorganic bases Chemical class 0.000 claims abstract description 5
- 238000003860 storage Methods 0.000 claims description 85
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 61
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- 235000010288 sodium nitrite Nutrition 0.000 claims description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- 239000007788 liquid Substances 0.000 claims description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 16
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 14
- 238000001914 filtration Methods 0.000 claims description 9
- 235000019441 ethanol Nutrition 0.000 claims description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 7
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 claims description 6
- -1 hexamethylene Alkane Chemical class 0.000 claims description 6
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- AZFNGPAYDKGCRB-XCPIVNJJSA-M [(1s,2s)-2-amino-1,2-diphenylethyl]-(4-methylphenyl)sulfonylazanide;chlororuthenium(1+);1-methyl-4-propan-2-ylbenzene Chemical compound [Ru+]Cl.CC(C)C1=CC=C(C)C=C1.C1=CC(C)=CC=C1S(=O)(=O)[N-][C@@H](C=1C=CC=CC=1)[C@@H](N)C1=CC=CC=C1 AZFNGPAYDKGCRB-XCPIVNJJSA-M 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 235000010289 potassium nitrite Nutrition 0.000 claims description 2
- 239000004304 potassium nitrite Substances 0.000 claims description 2
- POECFFCNUXZPJT-UHFFFAOYSA-M sodium;carbonic acid;hydrogen carbonate Chemical compound [Na+].OC(O)=O.OC([O-])=O POECFFCNUXZPJT-UHFFFAOYSA-M 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 2
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 claims 2
- 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 claims 1
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 claims 1
- GQPLMRYTRLFLPF-UHFFFAOYSA-N nitrous oxide Inorganic materials [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- AFBBKYQYNPNMAT-UHFFFAOYSA-N 1h-1,2,4-triazol-1-ium-3-thiolate Chemical compound SC=1N=CNN=1 AFBBKYQYNPNMAT-UHFFFAOYSA-N 0.000 abstract description 9
- 239000000047 product Substances 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 239000000049 pigment Substances 0.000 abstract 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 12
- 235000011121 sodium hydroxide Nutrition 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 8
- 229910021538 borax Inorganic materials 0.000 description 6
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 239000004328 sodium tetraborate Substances 0.000 description 6
- 235000010339 sodium tetraborate Nutrition 0.000 description 6
- 230000002363 herbicidal effect Effects 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 239000004009 herbicide Substances 0.000 description 3
- BHISMPFNRVMPFN-UHFFFAOYSA-N 1-bromo-2,3,4-trimethylbenzene Chemical compound CC1=CC=C(Br)C(C)=C1C BHISMPFNRVMPFN-UHFFFAOYSA-N 0.000 description 2
- NJOHZAYMOQWQTG-UHFFFAOYSA-N 1-iodo-2,3,4-trimethylbenzene Chemical compound CC1=CC=C(I)C(C)=C1C NJOHZAYMOQWQTG-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- GGBJHURWWWLEQH-UHFFFAOYSA-N butylcyclohexane Chemical compound CCCCC1CCCCC1 GGBJHURWWWLEQH-UHFFFAOYSA-N 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000002572 peristaltic effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- JAAGHUBILRENEC-UHFFFAOYSA-N 1h-benzo[g]indazole Chemical compound C1=CC2=CC=CC=C2C2=C1C=NN2 JAAGHUBILRENEC-UHFFFAOYSA-N 0.000 description 1
- OSKSVLBJJXQUPI-UHFFFAOYSA-N 2h-triazole-4-carboxamide Chemical class NC(=O)C1=CNN=N1 OSKSVLBJJXQUPI-UHFFFAOYSA-N 0.000 description 1
- USWWPAKLTNIJFL-UHFFFAOYSA-N 4-phenylsulfanyl-2h-triazole Chemical class C=1C=CC=CC=1SC1=CNN=N1 USWWPAKLTNIJFL-UHFFFAOYSA-N 0.000 description 1
- 241000208340 Araliaceae Species 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 229940033495 antimalarials Drugs 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical compound [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 description 1
- 229940112669 cuprous oxide Drugs 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- FWFGVMYFCODZRD-UHFFFAOYSA-N oxidanium;hydrogen sulfate Chemical compound O.OS(O)(=O)=O FWFGVMYFCODZRD-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/12—Oxygen or sulfur atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of methods for preparing benzene sulphur azoles, comprising the following steps: mixes trimethyl aniline and inorganic acid aqueous solution, is configured to ammonium salt solution；By 3- sulfydryl -1,2,4- triazole, inorganic base and the mixing of alkane alcohol are made into triazole solution；Enter the first tubular reactor after ammonium salt solution, nitrite aqueous solution and atent solvent mixing and carries out diazo-reaction, material after diazo-reaction is mixed with triazole solution, reaction promoter, mixed liquor, which enters back into, carries out denitrification reaction in the second tubular reactor, material after denitrification reaction carries out stratification, after layer acid adding of fetching water adjusts pH value, it is centrifugally separating to obtain solid crude product, it is dry, white or flaxen solid are obtained, the benzene sulphur azoles is obtained.The present invention operates continuously mode using pipe reaction, it is easier to realize automation technolo, improve production efficiency.It introduces atent solvent and enters diazotising and denitrification reaction, the purity of product can be improved with other foreign pigments such as situ extracting tar.
Description
Technical field
The present invention relates to a kind of methods for preparing benzene sulphur azoles.
Background technique
Benzene sulphur azoles, the entitled 3- (2,4,6- trimethylphenyls are thio) -1 of chemistry, 2,4- triazoles are for synthesizing benzene sulfone azoles
Essential intermediate.Benzene sulfone azoles, Chinese areN,NDiethyl -3-(2,4,6- trimethylphenyl) sulfonyl -1H-1,
2,4- triazole -1- formamides are a kind of efficient, low toxicity, the wide triazolylamide herbicide of herbicidal spectrum.Water can be effectively prevented
The growth of semen euphorbiae in rice field, while to person poultry harmless, it is a kind of environmentally protective herbicide.
Currently, the method for synthesis benzene sulphur azoles is broadly divided into following two categories, first method is with equal trimethyl iodobenzene or
Trimethyl bromobenzene and 3- sulfydryl -1,2,4- triazole is raw material, using DMF as solvent, under the action of potassium carbonate or cuprous oxide,
Substitution reaction occurs, obtains target product benzene sulphur azoles (Preparation of herbicidal 3- (2,4,6-
trialkylphenylthio)-1H-1,2,4-triazole compounds. EP 0718291A 1996; Carbamoyl
triazoles, known serine protease Inhibitors, are a potent new class of
antimalarials. J. Med. Chem. 2015, 58(16), 6448–6455.).Benzene sulphur azoles is prepared in this way, is deposited
In following deficiency:
1) trimethyl iodobenzene and equal trimethyl bromobenzene are expensive, and cost of material is high, do not have application value.
2) reaction condition is harsher, and the reaction time is long.
Second method is reported using trimethyl aniline as raw material, first through diazo-reaction, afterwards with 3- sulfydryl -1,2,4-
Denitrification reaction occurs for triazole, obtains target product benzene sulphur azoles (Preparation of phenylthiotriazole
derivatives as intermediates for herbicides. JPH 08176117A 1994；The synthesis of benzene sulfone azoles
And application study, Shanghai chemical industry, 2005,30(2), 16-18.).This method cost of material is much lower compared with former approach, but receives
Rate only has 70 ~ 78%, and has a large amount of diazonium salts to generate and accumulate in reaction process, and autoclave mode security risk is very big；Denitrification reaction
When release a large amount of nitrogen, autoclave denitrification process is easy to happen slug accident.
Summary of the invention
For technical problem of the existing technology, the purpose of the present invention is to provide a kind of methods for preparing benzene sulphur azoles.
A method of preparing benzene sulphur azoles, it is characterised in that the following steps are included: by trimethyl aniline and inorganic sour water
Solution mixing, is configured to ammonium salt solution；By 3- sulfydryl -1,2, it is molten to be configured to triazole for 4- triazole, inorganic base and the mixing of alkane alcohol
Liquid；Enter the first tubular reactor after ammonium salt solution, nitrite aqueous solution and atent solvent mixing and carries out diazo-reaction, weight
Material after nitridation reaction is mixed with triazole solution, reaction promoter, mixed liquor enter back into the second tubular reactor into
Row denitrification reaction, the material after denitrification reaction carry out stratification, are divided into water layer and atent solvent layer, water layer add acid for adjusting pH=
3 ~ 4, it is centrifugally separating to obtain solid crude product, it is dry, white or flaxen solid are obtained, the benzene sulphur azoles is obtained.
A kind of method preparing benzene sulphur azoles, it is characterised in that specifically includes the following steps:
1) ammonium salt solution, sodium nitrite in aqueous solution, atent solvent, triazole solution and reaction promoter be respectively placed in the first storage tank,
Material in second storage tank, third storage tank, the 4th storage tank and the 5th storage tank, in the first storage tank, the second storage tank and third storage tank
It is conveyed respectively by metering pump, into being mixed in the first mixer, the mixed liquor in the first mixer enters back into the first pipe
Formula reactor carries out diazo-reaction at -5 ~ 20 DEG C；
2) material in the material after the diazo-reaction of the first tubular reactor of step 1) outflow, the 4th storage tank and the 5th storage tank
It is mixed in into the second mixer, the mixed liquor in the second mixer enters back into the second tubular reactor, at 0 ~ 60 DEG C
Denitrification reaction is carried out, the material after the denitrification reaction of the second tubular reactor outflow, which enters, collects kettle progress stratification, is divided into
Water layer and atent solvent layer, after water layer adds acid for adjusting pH=3 ~ 4, into centrifuge, centrifugal filtration obtains solid crude product, solid
Crude product is dry after being washed with water, and obtains white or flaxen solid, obtains the benzene sulphur azoles.
A kind of method preparing benzene sulphur azoles, it is characterised in that inorganic acid aqueous solution is aqueous hydrochloric acid solution, sulfuric acid water
Solution or aqueous solution of nitric acid；Inorganic base is sodium hydroxide；Alkane alcohol is methanol, ethyl alcohol or propyl alcohol, preferably methanol；Nitrite
Aqueous solution is the aqueous solution of sodium nitrite or potassium nitrite.
A kind of method preparing benzene sulphur azoles, it is characterised in that inorganic acid aqueous solution is aqueous hydrochloric acid solution, the salt
The mass concentration of aqueous acid is 20 ~ 35%；Nitrite aqueous solution is sodium nitrite in aqueous solution, the sodium nitrite in aqueous solution
Mass concentration be 20 ~ 60%.
A kind of method preparing benzene sulphur azoles, it is characterised in that atent solvent is toluene, hexamethylene, normal heptane or first
Butylcyclohexane.
A kind of method preparing benzene sulphur azoles, it is characterised in that reaction promoter is borax-aqueous sodium carbonate, boron
Sand-sodium hydrate aqueous solution or sodium carbonate-bicarbonate aqueous solution.
A kind of method preparing benzene sulphur azoles, it is characterised in that the temperature of diazo-reaction is -5 ~ 20 DEG C, diazotising
The time of reaction is 1 ~ 90s；The temperature of denitrification reaction is 0 ~ 60 DEG C, and the time of denitrification reaction is 50 ~ 300s.
A kind of method preparing benzene sulphur azoles, it is characterised in that carry out diazo-reaction when, trimethyl aniline and
The charging molar flow ratio of sodium nitrite is 1:0.9 ~ 1.5.
A kind of method preparing benzene sulphur azoles, it is characterised in that the mesitylene of step 1) progress diazo-reaction
The charging molar flow of amine, 3- sulfydryl -1,2 of denitrification reaction is carried out with step 2, and the ratio of the charging molar flow of 4- triazole is
1:0.9~5。
Compared with prior art, the beneficial effects of the present invention are embodied in:
It replaces the tank reactor of the prior art to carry out diazonium-denitrification reaction with tubular reactor, can accurately control reaction ginseng
Number, reaction mass transfer heat transfer efficiency are high；And tank reactor is used, heat-transfer effect is poor, is easy to appear hot-spot, occurs secondary anti-
It answers.In tubular reactor, plug flow reaction is carried out, material reduces the generation of consecutive side reaction almost without back-mixing significantly；
And in tank reactor, for material close to complete mixing flow, back-mixing is serious, and reactant is easily contacted with product, macromolecular coupling easily generated
By-product.Using tubular reactor, online reacting dose is small, improves essential safety.Meanwhile pipe reaction uses continuous operation side
Formula, it is easier to realize automation technolo, improve production efficiency.It introduces atent solvent and enters diazotising and denitrification reaction, it can be with
Situ extracting impurity improves the purity of product.Reaction promoter is introduced simultaneously to inhibit the appearance of denitrification process side reaction and promote de-
Nitrogen reaction, the introducing of reaction promoter can make denitrification process be in a suitable soda acid ring with the pH value of balanced reaction system
In border.Because reaction solution acidity is too strong, it will lead to sulphur anionic amphiphilic nuclear capability decrease, be not susceptible to coupling reaction, and reaction solution
Alkalinity is too strong, then intramolecular coupling reaction easily occurs, and generates benzo indazole, reduces yield.
Detailed description of the invention
Fig. 1 is the process flow chart that the present invention prepares benzene sulphur azoles；
In figure: T1- the first storage tank, T2- the second storage tank, T3Third storage tank, T4- the four storage tank, T5- the five storage tank, R1- the first pipe
Formula reactor, R2- the second tubular reactor.
Specific embodiment
The present invention is further explained in the light of specific embodiments, but the scope of protection of the present invention is not limited thereto.
In following example 2 ~ 7, reaction equation is as follows:
。
Embodiment 1 (caldron process comparative example):
135 g(1 mol) trimethyl aniline, the aqueous hydrochloric acid solution that 365 g concentration are 30% and 400 g water are made into ammonium salt
Solution, ammonium salt solution are placed in a 2 L three-necked flasks, carry out mechanical stirring to the ammonium salt solution in three-necked flask, and in -5
Start that sodium nitrite in aqueous solution (the sodium nitrite in aqueous solution configuration method are as follows: 76 g sodium nitrites are molten prepared in advance is added dropwise at DEG C
In 150 g water), diazo-reaction is carried out, the rate of addition for controlling sodium nitrite in aqueous solution makes reaction temperature be no more than -2 DEG C, in
Completion of dropwise addition after 40 min, diazo-reaction terminate, the feed liquid after collecting diazo reaction.
3- sulfydryl -1,2 of 122 g, 4- triazole and 100 g sodium hydroxides are dissolved in 400 g methanol, are configured to triazole methanol
Solution.Configured triazole methanol solution is added in another 2 L three-necked flask, after diazo reaction obtained above
Feed liquid delivered into the three-necked flask containing triazole methanol solution by peristaltic pump, the revolution for controlling peristaltic pump makes
Reacting liquid temperature is no more than 20 DEG C, and the completion of dropwise addition after 30 min increases the temperature of reaction solution, in 30 DEG C of 40 min of reaction.Instead
After answering, in reaction solution plus acid for adjusting pH is to 3 ~ 4, and solid crude product is obtained by filtration, and solid crude product is washed with water, and then dries,
Obtaining 131.4 g(0.6 mol) white solid is benzene sulphur azoles, yield 60%, content 97.8%.
Embodiment 2:
By 1.35 kg(10 mol) trimethyl aniline, the aqueous hydrochloric acid solution and 3.50 kg water that 5.84 kg concentration are 25% are matched
At ammonium salt solution, it is placed in the first storage tank.It is water-soluble that 1.04 kg(15 mol) sodium nitrite and 4.16 kg water are made into sodium nitrite
Liquid is placed in the second storage tank.0.70 kg(7 mol) normal heptane is placed in third storage tank.By sulfydryl -1 3- 1.22 kg(12 mol),
2,4- triazoles, 0.80 kg(20 mol) sodium hydroxide and 5.50 kg methanol are made into triazole solution, it is placed in the 4th storage tank.It will
The solution that 0.25 kg borax and 0.50 kg sodium carbonate and 4.25 kg water are made into is placed in the 5th storage tank.
Material in first storage tank, the second storage tank and third storage tank is conveyed by metering pump respectively, into the first mixing
It is mixed in device, adjusting flow by metering pump makes the trimethyl aniline entered in the first mixer, sodium nitrite, positive heptan
The molar flow ratio of alkane is 1:1.5:0.7, and the mixed liquor in the first mixer enters back into the first tubular reactor, at -5 DEG C
Diazo-reaction is carried out, after reacting 30 s, the material after diazo-reaction is flowed out from the first tubular reactor.
Material in 4th storage tank and the 5th storage tank is conveyed by metering pump respectively, into the second mixer, while the
Material after the diazo-reaction of one tubular reactor outflow enters in the second mixer, is mixed in the second mixer,
It controls into equal trimethyl in the first mixer of molar flow and above-mentioned entrance of 3- sulfydryl -1,2,4- triazole in the second mixer
The ratio of the molar flow of aniline is 1.2:1, and the mixed liquor in the second mixer enters back into the second tubular reactor, at 0 DEG C into
Row denitrification reaction, after reacting 120 s, the material after denitrification reaction is flowed out from the second tubular reactor, is carried out into collecting in kettle
Stratification is divided into normal heptane layer and water layer, and liquid separation removes normal heptane layer, and water intaking layer adds acid for adjusting pH to 3 ~ 4, into centrifugation
Machine, centrifugal filtration obtain solid crude product, and solid crude product is dry after being washed with water, and 1.77 obtained kg white solids are benzene sulphur
Azoles (8.1 mol), yield 81%, content 98.6%.
Embodiment 3 prepares benzene sulphur azoles:
By 1.35 kg(10 mol) trimethyl aniline, the aqueous hydrochloric acid solution and 4.00 kg water that 3.65 kg concentration are 30% are matched
At ammonium salt solution, it is placed in the first storage tank.It is water-soluble that 0.62 kg(9 mol) sodium nitrite and 0.31 kg water are made into sodium nitrite
Liquid is placed in the second storage tank.0.66 kg(8 mol) toluene is placed in third storage tank.By sulfydryl -1,2 3- 1.52 kg(15 mol),
4- triazole, 1.20kg(30 mol) sodium hydroxide and 6.00 kg methanol are made into triazole solution, it is placed in the 4th storage tank.By 0.42
The solution that kg borax and 0.40 kg sodium hydroxide and 4.18 kg water are made into is placed in the 5th storage tank.
Material in first storage tank, the second storage tank and third storage tank is conveyed by metering pump respectively, into the first mixing
It is mixed in device, adjusting flow by metering pump makes the trimethyl aniline entered in the first mixer, sodium nitrite, toluene
Molar flow ratio be 1:0.9:0.8, the mixed liquor in the first mixer enters back into the first tubular reactor, carries out at 20 DEG C
Diazo-reaction, after reacting 15s, the material after diazo-reaction is flowed out from the first tubular reactor.
Material in 4th storage tank and the 5th storage tank is conveyed by metering pump respectively, into the second mixer, while the
Material after the diazo-reaction of one tubular reactor outflow enters in the second mixer, is mixed in the second mixer,
It controls into equal trimethyl in the first mixer of molar flow and above-mentioned entrance of 3- sulfydryl -1,2,4- triazole in the second mixer
The ratio of the molar flow of aniline is 1.5:1, and the mixed liquor in the second mixer enters back into the second tubular reactor, at 60 DEG C into
Row denitrification reaction, react 300s after, the material after denitrification reaction flow out from the second tubular reactor, into collection kettle in carry out it is quiet
Layering is set, toluene layer and water layer are divided into, liquid separation removes toluene layer, and water intaking layer adds acid for adjusting pH to 3 ~ 4, into centrifuge, centrifugation
Solid crude product is obtained by filtration, solid crude product is dry after being washed with water, and 1.86 obtained kg white solids are benzene sulphur azoles (8.5
Mol), yield 85%, content 98.9%.
Embodiment 4 prepares benzene sulphur azoles:
By 1.35 kg(10 mol) trimethyl aniline, the aqueous hydrochloric acid solution and 4.00 kg water that 2.77 kg concentration are 33% are matched
At ammonium salt solution, it is placed in the first storage tank.It is water-soluble that 0.76 kg(11 mol) sodium nitrite and 1.5 kg water are made into sodium nitrite
Liquid is placed in the second storage tank.0.42 kg(5 mol) hexamethylene is placed in third storage tank.By sulfydryl -1 3- 1.22 kg(12 mol),
2,4- triazoles, 1.00 kg(25 mol) sodium hydroxide and 8.00 kg methanol are made into triazole solution, it is placed in third storage tank.It will
The solution that 0.36 kg borax and 0.70 kg sodium carbonate and 3.94 kg water are made into is placed in the 5th storage tank.
Material in first storage tank, the second storage tank and third storage tank is conveyed by metering pump respectively, into the first mixing
It is mixed in device, adjusting flow by metering pump makes the trimethyl aniline entered in the first mixer, sodium nitrite, hexamethylene
The molar flow ratio of alkane is 1:1.1:0.5, and the mixed liquor in the first mixer enters back into the first tubular reactor, at 0 DEG C into
Row diazo-reaction, after reacting 10s, the material after diazo-reaction is flowed out from the first tubular reactor.
Material in 4th storage tank and the 5th storage tank is conveyed by metering pump respectively, into the second mixer, while the
Material after the diazo-reaction of one tubular reactor outflow enters in the second mixer, is mixed in the second mixer,
It controls into equal trimethyl in the first mixer of molar flow and above-mentioned entrance of 3- sulfydryl -1,2,4- triazole in the second mixer
The ratio of the molar flow of aniline is 1.2:1, and the mixed liquor in the second mixer enters back into the second tubular reactor, at 25 DEG C into
Row denitrification reaction, react 150s after, the material after denitrification reaction flow out from the second tubular reactor, into collection kettle in carry out it is quiet
Layering to be set, is divided into hexamethylene layer and water layer, liquid separation removes hexamethylene layer, and water intaking layer adds acid for adjusting pH to 3 ~ 4, into centrifuge,
Centrifugal filtration obtains solid crude product, and solid crude product is dry after being washed with water, and 1.99 obtained kg white solids are benzene sulphur azoles
(9.1mol), yield 91%, content 97.8%.
Embodiment 5
By 1.35 kg(10 mol) trimethyl aniline, the aqueous hydrochloric acid solution and 5.00 kg water that 2.43 kg concentration are 30% are matched
At ammonium salt solution, it is placed in the first storage tank.It is water-soluble that 0.83 kg(12 mol) sodium nitrite and 1.60 kg water are made into sodium nitrite
Liquid is placed in the second storage tank.0.69 kg(7 mol) hexahydrotoluene is placed in third storage tank.By 5.08 kg(50 mol) 3- mercapto
Base -1,2,4- triazole, 3.2 kg(80 mol) sodium hydroxide and 15.00 kg methanol are made into triazole solution, it is placed in the 4th storage
Tank.The solution that 0.45 kg borax and 0.80 kg sodium carbonate and 3.75 kg water are made into is placed in the 5th storage tank.
Material in first storage tank, the second storage tank and third storage tank is conveyed by metering pump respectively, into the first mixing
It is mixed in device, adjusting flow by metering pump makes the trimethyl aniline entered in the first mixer, sodium nitrite, methyl
The molar flow ratio of hexamethylene is 1:1.2:0.7, and the mixed liquor in the first mixer enters back into the first tubular reactor, in 0 DEG C
Lower carry out diazo-reaction, after reacting 5s, the material after diazo-reaction is flowed out from the first tubular reactor.
Material in 4th storage tank and the 5th storage tank is conveyed by metering pump respectively, into the second mixer, while the
Material after the diazo-reaction of one tubular reactor outflow enters in the second mixer, is mixed in the second mixer,
It controls into equal trimethyl in the first mixer of molar flow and above-mentioned entrance of 3- sulfydryl -1,2,4- triazole in the second mixer
The ratio of the molar flow of aniline is 5:1, and the mixed liquor in the second mixer enters back into the second tubular reactor, carries out at 40 DEG C
Denitrification reaction, after reacting 50s, the material after denitrification reaction is flowed out from the second tubular reactor, is stood into collecting in kettle
Layering, is divided into hexahydrotoluene layer and water layer, and liquid separation removes hexahydrotoluene layer, and water intaking layer adds acid for adjusting pH to 3 ~ 4, into from
Scheming, centrifugal filtration obtain solid crude product, and solid crude product is dry after being washed with water, and 1.82 obtained kg white solids are benzene
Sulphur azoles (8.3 mol), yield 83%, purity 98.3%.
Embodiment 6
By 1.35 kg(10 mol) trimethyl aniline, the aqueous hydrochloric acid solution and 4.00 kg water that 10.95 kg concentration are 20%
It is made into ammonium salt solution, is placed in the first storage tank.0.83 kg(12 mol) sodium nitrite and 1.52 kg water are made into sodium nitrite water
Solution is placed in the second storage tank.0.80 kg(8 mol) normal heptane is placed in third storage tank.By 0.91 kg(9 mol) 3- sulfydryl-
1,2,4- triazole, 1.20 kg(30 mol) sodium hydroxide and 6.00 kg methanol are made into triazole solution, it is placed in the 4th storage tank.It will
The solution that 0.15 kg borax and 0.60 kg sodium carbonate and 4.25 kg water are made into is placed in the 5th storage tank.
Material in first storage tank, the second storage tank and third storage tank is conveyed by metering pump respectively, into the first mixing
It is mixed in device, adjusting flow by metering pump makes the trimethyl aniline entered in the first mixer, sodium nitrite, positive heptan
The molar flow ratio of alkane is 1:1.2:0.8, and the mixed liquor in the first mixer enters back into the first tubular reactor, at 0 DEG C into
Row diazo-reaction, after reacting 15s, the material after diazo-reaction is flowed out from the first tubular reactor.
Material in 4th storage tank and the 5th storage tank is conveyed by metering pump respectively, into the second mixer, while the
Material after the diazo-reaction of one tubular reactor outflow enters in the second mixer, is mixed in the second mixer,
It controls into equal trimethyl in the first mixer of molar flow and above-mentioned entrance of 3- sulfydryl -1,2,4- triazole in the second mixer
The ratio of the molar flow of aniline is 0.9:1, and the mixed liquor in the second mixer enters back into the second tubular reactor, at 50 DEG C into
Row denitrification reaction, react 135s after, the material after denitrification reaction flow out from the second tubular reactor, into collection kettle in carry out it is quiet
Layering to be set, is divided into normal heptane layer and water layer, liquid separation removes normal heptane layer, and water intaking layer adds acid for adjusting pH to 3 ~ 4, into centrifuge,
Centrifugal filtration obtains solid crude product, and solid crude product is dry after being washed with water, and 1.88 obtained kg white solids are benzene sulphur azoles
(8.6 mol), yield 86%, content 95.6%.
Embodiment 7
By 1.35 kg(10 mol) trimethyl aniline, the aqueous hydrochloric acid solution and 4.00 kg water that 2.71 kg concentration are 35% are matched
At ammonium salt solution, it is placed in the first storage tank.It is water-soluble that 0.70 kg(10.2 mol) sodium nitrite and 2 kg water are made into sodium nitrite
Liquid is placed in the second storage tank.0.40 kg(4 mol) normal heptane is placed in third storage tank.By sulfydryl -1 3- 1.22 kg(12 mol),
2,4- triazoles, 0.8 kg(20 mol) sodium hydroxide and 6.00 kg methanol are made into triazole solution, it is placed in the 4th storage tank.It will
The solution that 0.35 kg borax and 0.40 kg sodium carbonate and 4.25 kg water are made into is placed in the 5th storage tank.
Material in first storage tank, the second storage tank and third storage tank is conveyed by metering pump respectively, into the first mixing
It is mixed in device, adjusting flow by metering pump makes the trimethyl aniline entered in the first mixer, sodium nitrite and just
The molar flow ratio of heptane is 1:1.02:0.4, and the mixed liquor in the first mixer enters back into the first tubular reactor, at 0 DEG C
Diazo-reaction is carried out, after reacting 12 s, the material after diazo-reaction is flowed out from the first tubular reactor.
Material in 4th storage tank and the 5th storage tank is conveyed by metering pump respectively, into the second mixer, while the
Material after the diazo-reaction of one tubular reactor outflow enters in the second mixer, is mixed in the second mixer,
It controls into equal trimethyl in the first mixer of molar flow and above-mentioned entrance of 3- sulfydryl -1,2,4- triazole in the second mixer
The ratio of the molar flow of aniline is 1.2:1, and the mixed liquor in the second mixer enters back into the second tubular reactor, at 25 DEG C into
Row denitrification reaction, react 90 s after, the material after denitrification reaction flow out from the second tubular reactor, into collection kettle in carry out it is quiet
Layering to be set, is divided into normal heptane layer and water layer, liquid separation removes normal heptane layer, and water intaking layer adds acid for adjusting pH to 3 ~ 4, into centrifuge,
Centrifugal filtration obtains solid crude product, and solid crude product is dry after being washed with water, and 1.84 obtained kg white solids are benzene sulphur azoles
(8.7 mol), yield 87%, content 98.3%.
Content described in this specification is only to enumerate to inventive concept way of realization, and protection scope of the present invention is not answered
When the concrete form for being seen as limited by embodiment and being stated, protection scope of the present invention is also only in those skilled in the art's root
According to present inventive concept it is conceivable that equivalent technologies mean.
Claims (9)
1. a kind of method for preparing benzene sulphur azoles, it is characterised in that the following steps are included: trimethyl aniline and inorganic acid is water-soluble
Liquid mixing, is configured to ammonium salt solution；By 3- sulfydryl -1,2, it is molten to be configured to triazole for 4- triazole, inorganic base and the mixing of alkane alcohol
Liquid；Enter the first tubular reactor after ammonium salt solution, nitrite aqueous solution and atent solvent mixing and carries out diazo-reaction, weight
Material after nitridation reaction is mixed with triazole solution, reaction promoter, mixed liquor enter back into the second tubular reactor into
Row denitrification reaction, the material after denitrification reaction carry out stratification, are divided into water layer and atent solvent layer, water layer add acid for adjusting pH=
3 ~ 4, it is centrifugally separating to obtain solid crude product, it is dry, white or flaxen solid are obtained, the benzene sulphur azoles is obtained.
2. a kind of method for preparing benzene sulphur azoles according to claim 1, it is characterised in that specifically includes the following steps:
1) ammonium salt solution, sodium nitrite in aqueous solution, atent solvent, triazole solution and reaction promoter be respectively placed in the first storage tank,
Material in second storage tank, third storage tank, the 4th storage tank and the 5th storage tank, in the first storage tank, the second storage tank and third storage tank
It is conveyed respectively by metering pump, into being mixed in the first mixer, the mixed liquor in the first mixer enters back into the first pipe
Formula reactor carries out diazo-reaction at -5 ~ 20 DEG C；
2) material in the material after the diazo-reaction of the first tubular reactor of step 1) outflow, the 4th storage tank and the 5th storage tank
It is mixed in into the second mixer, the mixed liquor in the second mixer enters back into the second tubular reactor, at 0 ~ 60 DEG C
Denitrification reaction is carried out, the material after the denitrification reaction of the second tubular reactor outflow, which enters, collects kettle progress stratification, is divided into
Water layer and atent solvent layer, after water layer adds acid for adjusting pH=3 ~ 4, into centrifuge, centrifugal filtration obtains solid crude product, solid
Crude product is dry after being washed with water, and obtains white or flaxen solid, obtains the benzene sulphur azoles.
3. a kind of method for preparing benzene sulphur azoles according to claim 1, it is characterised in that inorganic acid aqueous solution is hydrochloric acid water
Solution, aqueous sulfuric acid or aqueous solution of nitric acid；Inorganic base is sodium hydroxide；Alkane alcohol is methanol, ethyl alcohol or propyl alcohol, preferably first
Alcohol；Nitrite aqueous solution is the aqueous solution of sodium nitrite or potassium nitrite.
4. a kind of method for preparing benzene sulphur azoles according to claim 3, it is characterised in that inorganic acid aqueous solution is hydrochloric acid water
Solution, the mass concentration of the aqueous hydrochloric acid solution are 20 ~ 35%；Nitrite aqueous solution is sodium nitrite in aqueous solution, the nitrous
The mass concentration of acid sodium aqueous solution is 20 ~ 60%.
5. a kind of method for preparing benzene sulphur azoles according to claim 1, it is characterised in that atent solvent is toluene, hexamethylene
Alkane, normal heptane or hexahydrotoluene.
6. a kind of method for preparing benzene sulphur azoles according to claim 1, it is characterised in that reaction promoter is borax-sodium carbonate
Aqueous solution, borax-sodium hydrate aqueous solution or sodium carbonate-bicarbonate aqueous solution.
7. a kind of method for preparing benzene sulphur azoles according to claim 1, it is characterised in that the temperature of diazo-reaction be -5 ~
20 DEG C, the time of diazo-reaction is 1 ~ 90s；The temperature of denitrification reaction is 0 ~ 60 DEG C, and the time of denitrification reaction is 50 ~ 300s.
8. a kind of method for preparing benzene sulphur azoles according to claim 1, it is characterised in that when carrying out diazo-reaction, equal three
The charging molar flow ratio of methylaniline and sodium nitrite is 1:0.9 ~ 1.5.
9. a kind of method for preparing benzene sulphur azoles according to claim 2, it is characterised in that step 1) carries out diazo-reaction
Trimethyl aniline charging molar flow, 3- sulfydryl -1,2 of denitrification reaction is carried out with step 2, the charging of 4- triazole rubs
The ratio of your flow is 1:0.9 ~ 5.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2014116962A1 (en) * | 2013-01-24 | 2014-07-31 | Trustees Of Boston University | Selective histone deacetylase 8 inhibitors |
| CN106187711A (en) * | 2016-07-06 | 2016-12-07 | 浙江工业大学 | Method for preparing 2, 5-dichlorophenol by tubular diazotization and special device |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014116962A1 (en) * | 2013-01-24 | 2014-07-31 | Trustees Of Boston University | Selective histone deacetylase 8 inhibitors |
| CN106187711A (en) * | 2016-07-06 | 2016-12-07 | 浙江工业大学 | Method for preparing 2, 5-dichlorophenol by tubular diazotization and special device |
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| 周鹏等: "苯砜唑的合成和应用研究", 《上海化工》 * |
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Application publication date: 20190118 |