CN108863820A - A kind of synthetic method of substituted o-phenylenediamine - Google Patents
A kind of synthetic method of substituted o-phenylenediamine Download PDFInfo
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- CN108863820A CN108863820A CN201810853500.8A CN201810853500A CN108863820A CN 108863820 A CN108863820 A CN 108863820A CN 201810853500 A CN201810853500 A CN 201810853500A CN 108863820 A CN108863820 A CN 108863820A
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- synthetic method
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- bromine
- dimethyl
- fluorophenyl
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- 238000010189 synthetic method Methods 0.000 title claims abstract description 21
- 150000004987 o-phenylenediamines Chemical class 0.000 title claims abstract description 13
- -1 nitro, methoxycarbonyl group Chemical group 0.000 claims abstract description 27
- 238000006243 chemical reaction Methods 0.000 claims abstract description 26
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 15
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 9
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 7
- 239000011737 fluorine Substances 0.000 claims abstract description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 6
- 150000003973 alkyl amines Chemical class 0.000 claims abstract description 6
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 6
- 239000000460 chlorine Substances 0.000 claims abstract description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 20
- 238000010438 heat treatment Methods 0.000 claims description 11
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- FTZQXOJYPFINKJ-UHFFFAOYSA-N 2-fluoroaniline Chemical class NC1=CC=CC=C1F FTZQXOJYPFINKJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 150000004705 aldimines Chemical class 0.000 claims description 2
- 238000009833 condensation Methods 0.000 claims description 2
- 230000005494 condensation Effects 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- 239000000243 solution Substances 0.000 description 20
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- MSAXLKSNGBPEES-UHFFFAOYSA-N (2-fluoro-4-nitrophenyl)-phenylmethanone Chemical compound FC1=CC([N+](=O)[O-])=CC=C1C(=O)C1=CC=CC=C1 MSAXLKSNGBPEES-UHFFFAOYSA-N 0.000 description 11
- 238000000034 method Methods 0.000 description 10
- 239000002994 raw material Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000007788 liquid Substances 0.000 description 8
- 239000012265 solid product Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 0 *CC(*)=N[C@]1C(F)=CC([N+]([O-])=O)=CC1 Chemical compound *CC(*)=N[C@]1C(F)=CC([N+]([O-])=O)=CC1 0.000 description 6
- BFCFYVKQTRLZHA-UHFFFAOYSA-N 1-chloro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1Cl BFCFYVKQTRLZHA-UHFFFAOYSA-N 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 238000013019 agitation Methods 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- RHDGNLCLDBVESU-UHFFFAOYSA-N but-3-en-4-olide Chemical compound O=C1CC=CO1 RHDGNLCLDBVESU-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- NIGQBLJUFJSTDT-UHFFFAOYSA-N (2-fluoro-6-nitrophenyl)-phenylmethanone Chemical compound [O-][N+](=O)C1=CC=CC(F)=C1C(=O)C1=CC=CC=C1 NIGQBLJUFJSTDT-UHFFFAOYSA-N 0.000 description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- 238000004176 ammonification Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 238000003760 magnetic stirring Methods 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- MIJDSYMOBYNHOT-UHFFFAOYSA-N 2-(ethylamino)ethanol Chemical compound CCNCCO MIJDSYMOBYNHOT-UHFFFAOYSA-N 0.000 description 2
- ASFHDZHFDYLKBH-UHFFFAOYSA-N 3-(2-pyrrolidin-1-ylethyl)benzene-1,2-diamine Chemical class NC1=CC=CC(CCN2CCCC2)=C1N ASFHDZHFDYLKBH-UHFFFAOYSA-N 0.000 description 2
- SJIIPNLROACISX-IZZDOVSWSA-N CN(C)/C=N/c(c(F)ccc1)c1[N+]([O-])=O Chemical compound CN(C)/C=N/c(c(F)ccc1)c1[N+]([O-])=O SJIIPNLROACISX-IZZDOVSWSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 150000001409 amidines Chemical class 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- ZRWCDOFVFSLMSW-UHFFFAOYSA-N n-fluoro-4-nitroaniline Chemical compound [O-][N+](=O)C1=CC=C(NF)C=C1 ZRWCDOFVFSLMSW-UHFFFAOYSA-N 0.000 description 2
- 229910052979 sodium sulfide Inorganic materials 0.000 description 2
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 description 1
- DATUDYKWTCYSMM-UHFFFAOYSA-N 8-bromo-3-methyl-1,7-dipropylpurine-2,6-dione Chemical compound CN1C(=O)N(CCC)C(=O)C2=C1N=C(Br)N2CCC DATUDYKWTCYSMM-UHFFFAOYSA-N 0.000 description 1
- HNWAEGUBVLHQFH-KPKJPENVSA-N CN(C)/C=N/C(C(F)=CCC=C1)=C1[N+]([O-])=O Chemical compound CN(C)/C=N/C(C(F)=CCC=C1)=C1[N+]([O-])=O HNWAEGUBVLHQFH-KPKJPENVSA-N 0.000 description 1
- JQIONGWYNIVQPZ-LFYBBSHMSA-N CN(C)/C=N/c(c(F)cc([N+]([O-])=O)c1)c1F Chemical compound CN(C)/C=N/c(c(F)cc([N+]([O-])=O)c1)c1F JQIONGWYNIVQPZ-LFYBBSHMSA-N 0.000 description 1
- BNVFQXNNQYCMER-WUXMJOGZSA-N CN(C)/C=N/c(c(F)ccc1)c1F Chemical compound CN(C)/C=N/c(c(F)ccc1)c1F BNVFQXNNQYCMER-WUXMJOGZSA-N 0.000 description 1
- NQWOFVQQGBNLAI-UHFFFAOYSA-N CN(C)CNC(C(CC1)F)=C(CBr)C=C1[N+]([O-])=O Chemical compound CN(C)CNC(C(CC1)F)=C(CBr)C=C1[N+]([O-])=O NQWOFVQQGBNLAI-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- WRXNJTBODVGDRY-UHFFFAOYSA-N NCCN1CCCC1 Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 1
- USMBUNXIODNBEL-UHFFFAOYSA-N Nc(c(Br)cc([N+]([O-])=O)c1)c1NCCN1CCCCC1 Chemical compound Nc(c(Br)cc([N+]([O-])=O)c1)c1NCCN1CCCCC1 USMBUNXIODNBEL-UHFFFAOYSA-N 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 238000005915 ammonolysis reaction Methods 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000005485 electric heating Methods 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- NPOLCELBYKFCMB-UHFFFAOYSA-N n-fluoro-2-nitroaniline Chemical compound [O-][N+](=O)C1=CC=CC=C1NF NPOLCELBYKFCMB-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 150000003235 pyrrolidines Chemical class 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000003303 reheating Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006273 synthetic pesticide Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of synthetic methods of substituted o-phenylenediamine, and by N'- (2- fluorophenyl)-N, N- dimethyl methyl amidine derivative is heated to 180~220 DEG C with alkylamine derivative and is reacted, be can be obtained；Reaction process is as follows：Wherein, R1For chlorine, bromine, nitro, methoxycarbonyl group, cyano or acetyl group, R2For hydrogen, fluorine, bromine, R3For 2- ethoxy, 2- methoxyethyl, (tetrahydrofuran -2- base) methyl, 2- (pyrrolidin-1-yl) ethyl.
Description
Technical field
The present invention relates to organic synthesis fields, and in particular to a kind of synthetic method of substituted o-phenylenediamine.
Background technique
O-phenylenediamine is a kind of important chemical intermediate, is mainly used for synthetic pesticide, dyestuff, auxiliary agent, photosensitive material etc.,
Tool has been widely used and vast market prospect.Since substituted o-phenylenediamine can synthesize the drugs such as antipsychotic, thus cure
Medicine industry by be o-phenylenediamine most development potentiality field.Substituted o-phenylenediamine is to be obtained by o-phenylenediamine by substitution reaction
?.Currently, industrialization or the synthetic route with industrial prospect only have 3, respectively o-nitrochlorobenzene ammonification akali sulphide
Reduction method, o-dichlorohenzene ammoniation process and o-nitrochlorobenzene ammonification catalytic hydrogenating reduction method.
O-nitrochlorobenzene ammonification sodium sulfide reducing method is using o-nitrochlorobenzene as starting material, with concentrated ammonia liquor at 180~190 DEG C
Lower reaction about 8h to get arrive ortho-nitraniline.Then gained ortho-nitraniline is used into sodium sulfide solution at a proper temperature again
Reduction reaction is carried out, through separation and purification operations up to product o-phenylenediamine.
O-dichlorohenzene ammoniation process using copper as catalyst, in autoclave by o-dichlorohenzene and concentrated ammonia liquor under higher temperature into
Row ammonolysis reaction can obtain o-phenylenediamine.
O-nitrochlorobenzene ammonification catalytic hydrogenating reduction method is using o-nitrochlorobenzene as starting material, with concentrated ammonia liquor 180~190
About 8h is reacted at DEG C to get ortho-nitraniline is arrived.Then catalyst and gained ortho-nitraniline are put into autoclave again,
It is passed through hydrogen, catalytic hydrogenation reaction is carried out at certain temperature and pressure, obtains product o-phenylenediamine.
However, no matter the synthesis of which kind of o-phenylenediamine can not avoid o-phenylenediamine when preparing substituted o-phenylenediamine
Synthesis, synthesis step are cumbersome.
Summary of the invention
In order to solve the deficiencies in the prior art, an object of the present invention is to provide a kind of synthesis side of substituted o-phenylenediamine
Method, preparation method are simple.
To achieve the goals above, the technical scheme is that：
A kind of synthetic method of substituted o-phenylenediamine, by N'- (2- fluorophenyl)-N, N- dimethyl methyl amidine derivative and alkyl
Amine derivative is heated to 150~220 DEG C and is reacted, and can be obtained；
Reaction process is as follows：
Wherein, R1For chlorine, bromine, nitro, methoxycarbonyl group, cyano or acetyl group, R2For hydrogen, fluorine, bromine, R3For 2- ethoxy, 2-
Methoxyethyl, (tetrahydrofuran -2- base) methyl, 2- (pyrrolidin-1-yl) ethyl.
It is an advantage of the invention that：
The present invention provides a kind of synthetic methods of new substituted o-phenylenediamine, and the synthetic method step is simple, high income.
Specific embodiment
It is noted that described further below be all exemplary, it is intended to provide further instruction to the application.Unless another
It indicates, all technical and scientific terms used herein has usual with the application person of an ordinary skill in the technical field
The identical meanings of understanding.
It should be noted that term used herein above is merely to describe specific embodiment, and be not intended to restricted root
According to the illustrative embodiments of the application.As used herein, unless the context clearly indicates otherwise, otherwise singular
Also it is intended to include plural form, additionally, it should be understood that, when in the present specification using term "comprising" and/or " packet
Include " when, indicate existing characteristics, step, operation, device, component and/or their combination.
As background technique is introduced, exist in the prior art existing synthesis substituted o-phenylenediamine be required to pass through neighbour
The substitution reaction of phenylenediamine, the deficiency of synthesis process complexity, in order to solve technical problem as above, present applicant proposes one kind to take
For the synthetic method of o-phenylenediamine.
A kind of exemplary embodiment of the application, provides a kind of synthetic method of substituted o-phenylenediamine, by N'- (2- fluorine
Phenyl)-N, N- dimethyl methyl amidine derivative is heated to 150~220 DEG C with alkylamine derivative and reacted, be can be obtained；
Reaction process is as follows：
Wherein, R1For chlorine, bromine, nitro, methoxycarbonyl group, cyano or acetyl group, R2For hydrogen, fluorine, bromine, R3For 2- ethoxy, 2-
Methoxyethyl, (tetrahydrofuran -2- base) methyl, 2- (pyrrolidin-1-yl) ethyl.
Preferably, R1For nitro, R2For hydrogen or bromine.
It is further preferred that N'- (2- fluorophenyl)-N, N- dimethyl methyl amidine derivative is selected from：
Preferably, R3For 2- ethoxy or 2- (pyrrolidin-1-yl) ethyl.
Preferably, the solvent used is dimethyl sulfoxide (DMSO), n,N-Dimethylformamide (DMF) or hexamethyl phosphoric acid
Triamide (HMPA).
Heating means be oil bath heating or microwave heating, the application is preferred, oil bath heating, steam heating, electric heating or
Microwave heating.
Preferably, the molar ratio of N'- (2- fluorophenyl)-N, N- dimethyl methyl amidine derivative and alkylamine derivative is 1:1
~20.
Preferably, the synthetic method of N'- (2- fluorophenyl)-N, N- the dimethyl methyl amidine derivative is：By 2- fluoroaniline
Derivative is reacted with N,N-dimethylformamide progress aldimine condensation can be obtained N'- (2- fluorophenyl)-N, N- dimethyl carbonamidine
Derivative；
Reaction process is as follows：
Wherein, R1For chlorine, bromine, nitro, methoxycarbonyl group, cyano or acetyl group, R2For hydrogen, fluorine, bromine, R3For 2- ethoxy, 2-
Methoxyethyl, (tetrahydrofuran -2- base) methyl, 2- (pyrrolidin-1-yl) ethyl.
It is further preferred that the catalyst used is benzene sulfonyl chloride.
It is further preferred that the molar ratio of 2- fluorobenzene amine derivative and benzene sulfonyl chloride is 1:1.5~2.5.
In order to enable those skilled in the art can clearly understand the technical solution of the application, below with reference to tool
The technical solution of the application is described in detail in the embodiment of body.
The synthesis of raw material：
(E)-N'- (the fluoro- 6- nitrobenzophenone of 2-)-N, N- dimethyl carbonamidine
DMF (60mL) is added into the round-bottomed flask equipped with the 250mL of magnetic stirring bar, benzene sulfonyl chloride (27.2g,
154mmol).Solution is stirred 20 minutes, the color of solution becomes light yellow.The addition fluoro- 6- nitroaniline of 2- (12g,
77mmol), mixture is stirred at room temperature 30 minutes.There are a large amount of solid products to generate, crosses filter solid, washed with ether, very
Sky is dry.Then resulting solid is transferred in the round-bottomed flask of another 250mL and is added NaOH (4M) solution (50mL) and
Ethyl acetate (150mL) neutralizes.It transfers the solution into funnel and separates, inorganic layer is extracted with 2 × 100mL ethyl acetate.Merge
After organic layer, it is washed with brine and 3 hours dry with anhydrous sodium sulfate, yellow solid (E)-N'- (2- is obtained after revolving
Fluoro- 6- nitrobenzophenone)-N, N- dimethyl carbonamidine, 15.5g, yield 95%.1H NMR(500MHz,DMSO-d6)δppm 2.97
(s, 3H), 3.08 (s, 3H), 7.35 (m, 1H), 7.79 (d, J=8.77,3.40Hz, 1H), 7.90 (dd, J=7.63,
2.75Hz,1H),7.98(s,1H)；13C NMR(126MHz,DMSO-d6)δppm 33.92,39.04,39.20,39.37,
39.53,39.70,39.87,39.96,40.04,116.10,116.14,116.20,116.39,117.21,117.28,
141.19,141.28,144.20,155.73,158.20,160.22；HRMS calcd.for C9H10FN3O2:211.0757,
found 211.0750.
(E)-N'- (the fluoro- 4- nitrobenzophenone of 2-)-N, N- dimethyl carbonamidine
DMF (60mL) is added into the round-bottomed flask equipped with the 250mL of magnetic stirring bar, benzene sulfonyl chloride (27.2g,
154mmol).Solution is stirred 20 minutes, the color of solution becomes light yellow.The addition fluoro- 4- nitroaniline of 2- (12g,
77mmol), mixture is stirred at room temperature 30 minutes.There are a large amount of solid products to generate, crosses filter solid, washed with ether, very
Sky is dry.Then resulting solid is transferred in the round-bottomed flask of another 250mL and is added NaOH (4M) solution (50mL) and
Ethyl acetate (150mL) neutralizes.It transfers the solution into funnel, separates, inorganic layer is extracted with 2 × 100mL ethyl acetate.Merge
After organic layer, it is washed with brine and 3 hours dry with anhydrous sodium sulfate, yellow solid (E)-N'- (2- is obtained after revolving
Fluoro- 4- nitrobenzophenone)-N, N- dimethyl carbonamidine, 13.2g, yield 81%.1H NMR(500MHz,DMSO-d6)δppm 2.95
(s,3H),3.07(s,3H),8.10(m,1H),7.97(m,1H),7.90(m,1H),7.98(s,1H)；13C NMR(126MHz,
DMSO-d6)δppm 33.91,39.02,39.21,39.40,39.52,39.71,39.88,39.97,40.03,116.09,
116.12,116.21,116.40,117.22,117.29,141.20,141.30,144.26,155.74,158.22,160.21；
HRMS calcd.for C9H10FN3O2:211.0757,found 211.0748.
(E)-N'- (the fluoro- 4- nitrobenzophenone of the bromo- 6- of 2-)-N, N- dimethyl carbonamidine
DMF (80mL) is added into the round-bottomed flask equipped with the 250mL of magnetic stirring bar, benzene sulfonyl chloride (27.2g,
154mmol).Solution is stirred 30 minutes, the color of solution becomes light yellow.The addition fluoro- 4- nitroaniline of 2- bromine 6- (18g,
77mmol), mixture is stirred at room temperature 50 minutes.There are a large amount of solid products to generate, crosses filter solid, washed with ether, very
Sky is dry.Then resulting solid is transferred in the round-bottomed flask of another 250mL and is added NaOH (4M) solution (60mL) and
Ethyl acetate (160mL) neutralizes.It transfers the solution into funnel, separates, inorganic layer is extracted with 3 × 100mL ethyl acetate.Merge
After organic layer, it is washed with brine and 6 hours dry with anhydrous sodium sulfate, yellow solid (E)-N'- (2- is obtained after revolving
The bromo- fluoro- 4- nitrobenzophenone of 6-)-N, N- dimethyl carbonamidine, 19.1g, yield 86%.1H NMR(500MHz,DMSO-d6)δppm
2.99(s,3H),3.05(s,3H),8.20(m,1H),7.99(m,1H),7.94(m,1H),7.88(s,1H)；13C NMR
(126MHz,DMSO-d6)δppm 33.90,39.01,39.28,39.42,39.51,39.72,39.87,39.93,40.05,
116.03,116.22,116.19,116.36,117.18,117.22,141.21,141.32,144.25,155.72,158.21,
160.25；HRMS calcd.for C9H9BrFN3O2:288.9862,found 288.9871.
Embodiment 1
(E)-N'- (the fluoro- 6- nitrobenzophenone of 2-)-N, N- dimethyl carbonamidine are added in the Biotage reaction tube of 20mL
(2mmol, 422mg), DMSO (12mL), 2- ethylaminoethanol (10mmol, 610mg) and a magnetic stir bar, reaction tube cover
It is placed into the oil bath with magnetic agitation afterwards and is heated to 180 DEG C, kept for 1 hour.TLC is analysis shows raw material (E)-N'- (2-
Fluoro- 6- nitrobenzophenone)-N, N- dimethyl carbonamidine, which disappears and has newly to put, to be occurred.LC-MS furanone target product generates.To anti-
It is poured into the 250mL round-bottomed flask that one fills water (50mL) and stirs 10 minutes after answering liquid cooling to room temperature.Then it will mix
Liquid is closed to be transferred in separatory funnel with ethyl acetate (4 × 50mL) extraction.After merging organic phase, washed with water (60mL), it is anhydrous
Sodium sulphate is 6 hours dry.Thick weak yellow liquid is obtained after revolving.Silica gel column chromatography (mobile phase：Ethyl acetate：N-hexane=
1：5) solid product 2- (2- amino -3- nitro-phenylamino) ethyl alcohol 305mg, yield 77% are obtained.1H NMR(500MHz,DMSO-
d6)δppm 2.23(br,1H),3.21(m,2H),4.12(br,1H),4.6(br,2H),7.60(s,1H),6.65(m,1H),
6.51(m,1H)；HRMS calcd.for C8H11N3O3:197.0800,found 197.0809.
Embodiment 2
(E)-N'- (the fluoro- 6- nitrobenzophenone of 2-)-N, N- dimethyl carbonamidine are added in the single necked round bottom flask of 50mL
(6mmol, 1.266g), DMSO (25mL), 2- ethylaminoethanol (30mmol, 1.83g) and a magnetic stir bar, reaction flask are put
Enter in the oil bath with magnetic agitation and is heated to reflux (189 DEG C) 2 hours.TLC is analysis shows raw material (E)-N'- (fluoro- 6- nitro of 2-
Phenyl)-N, N- dimethyl carbonamidine, which disappears and has newly to put, to be occurred.LC-MS furanone target product generates.It is cooled to room to reaction solution
It is poured into the 500mL round-bottomed flask that one fills water (150mL) and stirs 10 minutes after temperature.Then mixed liquor is transferred to
It is extracted in separatory funnel with ethyl acetate (3 × 160mL).It after merging organic phase, is washed with water (200mL), anhydrous sodium sulfate is dry
It is dry overnight.Thick weak yellow liquid is obtained after revolving.Silica gel column chromatography (mobile phase：Ethyl acetate：N-hexane=1：5) solid is obtained
Product 2- (2- amino -3- nitro-phenylamino) ethyl alcohol 1.01g, yield 85%.
Embodiment 3
(E)-N'- (the fluoro- 4- nitrobenzophenone of 2-)-N, N- dimethyl carbonamidine are added in the Biotage reaction tube of 20mL
(2mmol, 0.422g), DMSO (12mL), 2- (pyrrolidin-1-yl) ethamine (10mmol, 1.14g) and a magnetic stir bar,
Reaction tube is placed into the oil bath with magnetic agitation after covering is heated to 180 DEG C, is kept for 1 hour.TLC is analysis shows raw material
(E)-N'- (the fluoro- 4- nitrobenzophenone of 2-)-N, N- dimethyl carbonamidine still have, and continue after reheating 30 minutes, TLC analytical table
Bright raw material disappears.LC-MS furanone target product generates.It is poured into one after reaction solution is cooled to room temperature and fills water
In the 250mL round-bottomed flask of (50mL) and stir 10 minutes.Then mixed liquor is transferred in separatory funnel with ethyl acetate (3
× 50mL) extraction.It after merging organic phase, is washed with water (50mL), anhydrous sodium sulfate is 6 hours dry.It is obtained after revolving thick light
Yellow liquid.Silica gel column chromatography (mobile phase：Ethyl acetate：N-hexane=1：5) solid product 5- nitro N is obtained1(2- (pyrroles
Alkane -1- base) ethyl) benzene -1,2- diamines 0.398g, yield 80%.1H NMR(500MHz,DMSO-d6)δppm 1.66(m,4H),
2.28(t,4H),2.61(t,2H),3.19(m,2H),4.11(br,1H),4.58(br,2H),7.34(m,1H),7.19(s,
1H),6.49(m,1H)；HRMS calcd.for C12H18N4O2:250.1430,found 250.1442.
Embodiment 4
(E)-N'- (the fluoro- 4- nitrobenzophenone of 2-)-N, N- dimethyl carbonamidine are added in the Biotage reaction tube of 20mL
(2mmol, 0.422g), DMSO (12mL), 2- (pyrrolidin-1-yl) ethamine (10mmol, 1.14g) and a magnetic stir bar,
Reaction tube covers postposition and enters in microwave reacting furnace (Biotage).Heating reaction 20 minutes at 220 DEG C, TLC is analysis shows raw material
(E)-N'- (the fluoro- 4- nitrobenzophenone of 2-)-N, N- dimethyl carbonamidine raw material disappear.LC-MS furanone target product generates.To
Reaction solution is poured into the 250mL round-bottomed flask that one fills water (50mL) and stirs 10 minutes after being cooled to room temperature.Then will
Mixed liquor is transferred in separatory funnel to be extracted with ethyl acetate (3 × 50mL).After merging organic phase, washed with water (50mL), nothing
Aqueous sodium persulfate is 6 hours dry.Thick weak yellow liquid is obtained after revolving.Silica gel column chromatography (mobile phase：Ethyl acetate：N-hexane
=1：5) solid product 5- nitro N is obtained1(2- (pyrrolidin-1-yl) ethyl) benzene -1,2- diamines 0.371g, yield 74%.
Embodiment 5
(E)-N'- (the fluoro- 4- nitrobenzophenone of the bromo- 6- of 2-)-N, N- dimethyl methyl are added in the Biotage reaction tube of 20mL
Amidine (2mmol, 0.580g), DMSO (12mL), 2- (pyrrolidin-1-yl) ethamine (10mmol, 1.14g) and a magnetic agitation
Son, reaction tube is placed into the oil bath with magnetic agitation after covering is heated to 180 DEG C, is kept for 1 hour.TLC is analysis shows original
Expect (E)-N'- (the fluoro- 4- nitrobenzophenone of 2-)-N, N- dimethyl carbonamidine still has, continue to reheat 1 hour, TLC analysis shows
Raw material disappears.LC-MS furanone target product generates.It is poured into one after reaction solution is cooled to room temperature and fills water (50mL)
250mL round-bottomed flask in and stir 10 minutes.Then mixed liquor is transferred in separatory funnel with ethyl acetate (3 × 50mL)
Extraction.After merging organic phase, washed with water (50mL), anhydrous sodium sulfate is dried overnight.Thick weak yellow liquid is obtained after revolving.
Silica gel column chromatography (mobile phase：Ethyl acetate：N-hexane=1：6) the bromo- 5- nitro-N of solid product 3- is obtained1(2- (pyrrolidines -1-
Base) ethyl) benzene -1,2- diamines 0.290g, yield 44%.1H NMR(500MHz,DMSO-d6)δppm 1.65(m,4H),2.27
(t,4H),2.60(t,2H),3.20(m,2H),4.10(br,1H),4.60(br,2H),7.41(s,1H),7.23(s,1H),
6.49(m,1H)；HRMS calcd.for C12H17BrN4O2:328.0535,found 328.0527.
Embodiment 6
(E)-N'- (the fluoro- 4- nitrobenzophenone of the bromo- 6- of 2-)-N, N- dimethyl methyl are added in the Biotage reaction tube of 20mL
Amidine (2mmol, 0.580g), DMSO (12mL), 2- (pyrrolidin-1-yl) ethamine (10mmol, 1.14g) and a magnetic agitation
Son, reaction tube are placed into microwave reaction furnace (Biotage) after covering.Heating reaction 20 minutes, TLC analytical table at 220 DEG C
Bright raw material (E)-N'- (the fluoro- 4- nitrobenzophenone of the bromo- 6- of 2-)-N, N- dimethyl carbonamidine raw material disappear.LC-MS furanone target
Product generates.It is poured into after reaction solution is cooled to room temperature in the 250mL round-bottomed flask that one fills water (50mL) and stirs 10
Minute.Then mixed liquor is transferred in separatory funnel and is extracted with ethyl acetate (3 × 50mL).After merging organic phase, water is used
(50mL) washing, anhydrous sodium sulfate are 6 hours dry.Thick weak yellow liquid is obtained after revolving.Silica gel column chromatography (mobile phase：Second
Acetoacetic ester：N-hexane=1：6) the bromo- 5- nitro-N '-of solid product 3- (2- (pyrrolidin-1-yl) ethyl) benzene -1,2- diamines is obtained
0.255g, yield 39%.
The foregoing is merely preferred embodiment of the present application, are not intended to limit this application, for the skill of this field
For art personnel, various changes and changes are possible in this application.Within the spirit and principles of this application, made any to repair
Change, equivalent replacement, improvement etc., should be included within the scope of protection of this application.
Claims (10)
1. a kind of synthetic method of substituted o-phenylenediamine, characterized in that N'- (2- fluorophenyl)-N, N- dimethyl carbonamidine is derivative
Object is heated to 180~220 DEG C with alkylamine derivative and is reacted, and can be obtained；
Reaction process is as follows：
Wherein, R1For chlorine, bromine, nitro, methoxycarbonyl group, cyano or acetyl group, R2For hydrogen, fluorine, bromine, R3For 2- ethoxy, 2- methoxy
Ethyl, (tetrahydrofuran -2- base) methyl, 2- (pyrrolidin-1-yl) ethyl.
2. synthetic method as described in claim 1, characterized in that R1For nitro, R2For hydrogen or bromine.
3. synthetic method as claimed in claim 2, characterized in that the choosing of N'- (2- fluorophenyl)-N, N- dimethyl methyl amidine derivative
From：
4. synthetic method as described in claim 1, characterized in that R3For 2- ethoxy or 2- (pyrrolidin-1-yl) ethyl.
5. synthetic method as described in claim 1, characterized in that the solvent used is dimethyl sulfoxide (DMSO), N, N- bis-
Methylformamide (DMF) or hexamethylphosphoric triamide (HMPA).
6. synthetic method as described in claim 1, characterized in that heating means are oil bath heating or microwave heating.
7. synthetic method as described in claim 1, characterized in that N'- (2- fluorophenyl)-N, N- dimethyl methyl amidine derivative with
The molar ratio of alkylamine derivative is 1:1~20.
8. synthetic method as described in claim 1, characterized in that N'- (2- fluorophenyl)-N, N- the dimethyl carbonamidine is derivative
The synthetic method of object is：2- fluorobenzene amine derivative is reacted with N,N-dimethylformamide progress aldimine condensation can be obtained N'-
(2- fluorophenyl)-N, N- dimethyl methyl amidine derivative；
Reaction process is as follows：
Wherein, R1For chlorine, bromine, nitro, methoxycarbonyl group, cyano or acetyl group, R2For hydrogen, fluorine, bromine, R3For 2- ethoxy, 2- methoxy
Ethyl, (tetrahydrofuran -2- base) methyl, 2- (pyrrolidin-1-yl) ethyl.
9. synthetic method as claimed in claim 8, characterized in that the catalyst used is benzene sulfonyl chloride.
10. synthetic method as claimed in claim 8, characterized in that the molar ratio of 2- fluorobenzene amine derivative and benzene sulfonyl chloride is
1:1.5~2.5.
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| WO2009031822A2 (en) * | 2007-09-04 | 2009-03-12 | Korea Research Institute Of Chemical Technology | New fluorine-containing phenyl formamidine derivatives and their use as insecticide |
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| WO2009031822A2 (en) * | 2007-09-04 | 2009-03-12 | Korea Research Institute Of Chemical Technology | New fluorine-containing phenyl formamidine derivatives and their use as insecticide |
| CN106866545A (en) * | 2017-03-31 | 2017-06-20 | 刘雪静 | 1 cycloalkane 5 nitro 1H benzo [D] glyoxaline compound and preparation method thereof |
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