CN118439966A - Synthesis method of p-nitroaniline compound - Google Patents
Synthesis method of p-nitroaniline compound Download PDFInfo
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- CN118439966A CN118439966A CN202410896529.XA CN202410896529A CN118439966A CN 118439966 A CN118439966 A CN 118439966A CN 202410896529 A CN202410896529 A CN 202410896529A CN 118439966 A CN118439966 A CN 118439966A
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- compound
- amide
- nitrobenzene
- oxygen
- paranitroaniline
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- -1 p-nitroaniline compound Chemical class 0.000 title claims abstract description 67
- 238000001308 synthesis method Methods 0.000 title claims abstract description 15
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 claims abstract description 59
- 238000006243 chemical reaction Methods 0.000 claims abstract description 47
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 29
- 239000001301 oxygen Substances 0.000 claims abstract description 29
- 150000001408 amides Chemical class 0.000 claims abstract description 28
- 239000012298 atmosphere Substances 0.000 claims abstract description 26
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims abstract description 24
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims abstract description 24
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical class NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000002904 solvent Substances 0.000 claims abstract description 19
- 239000003513 alkali Substances 0.000 claims abstract description 16
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 7
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 6
- 238000010189 synthetic method Methods 0.000 claims abstract 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
- 239000012074 organic phase Substances 0.000 claims description 16
- 239000000376 reactant Substances 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 150000002431 hydrogen Chemical group 0.000 claims description 12
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 125000001931 aliphatic group Chemical group 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 238000004440 column chromatography Methods 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 238000000926 separation method Methods 0.000 claims description 8
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 8
- 230000002194 synthesizing effect Effects 0.000 claims description 8
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- ZMJZYXKPJWGDGR-UHFFFAOYSA-N aminosulfamic acid Chemical compound NNS(O)(=O)=O ZMJZYXKPJWGDGR-UHFFFAOYSA-N 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 4
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 239000011630 iodine Substances 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 3
- 150000005181 nitrobenzenes Chemical class 0.000 claims 1
- 229910052723 transition metal Inorganic materials 0.000 abstract description 10
- 150000003624 transition metals Chemical class 0.000 abstract description 10
- 239000003054 catalyst Substances 0.000 abstract description 4
- 230000007613 environmental effect Effects 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 2
- 230000002349 favourable effect Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 16
- 229940024606 amino acid Drugs 0.000 description 14
- 239000000047 product Substances 0.000 description 12
- 238000006555 catalytic reaction Methods 0.000 description 8
- 238000000605 extraction Methods 0.000 description 6
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 6
- 238000002156 mixing Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 3
- XCMUCRMMVDSVEL-UHFFFAOYSA-N 2-[(4-nitrobenzoyl)amino]acetic acid Chemical compound OC(=O)CNC(=O)C1=CC=C([N+]([O-])=O)C=C1 XCMUCRMMVDSVEL-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 2
- FZERHIULMFGESH-UHFFFAOYSA-N N-phenylacetamide Chemical compound CC(=O)NC1=CC=CC=C1 FZERHIULMFGESH-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000012776 electronic material Substances 0.000 description 2
- 229910001385 heavy metal Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ZDFBKZUDCQQKAC-UHFFFAOYSA-N 1-bromo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Br)C=C1 ZDFBKZUDCQQKAC-UHFFFAOYSA-N 0.000 description 1
- NAXBFPMPKBFNAJ-UHFFFAOYSA-N 1-nitro-4-(trifluoromethylsulfonyl)naphthalene Chemical compound [N+](=O)([O-])C1=CC=C(C2=CC=CC=C12)S(=O)(=O)C(F)(F)F NAXBFPMPKBFNAJ-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- CZGCEKJOLUNIFY-UHFFFAOYSA-N 4-Chloronitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1 CZGCEKJOLUNIFY-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229960001413 acetanilide Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000005915 ammonolysis reaction Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- DWKPPFQULDPWHX-VKHMYHEASA-N l-alanyl ester Chemical class COC(=O)[C@H](C)N DWKPPFQULDPWHX-VKHMYHEASA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- ZTCQFVRINYOPOH-UHFFFAOYSA-N n-(4-nitrophenyl)formamide Chemical compound [O-][N+](=O)C1=CC=C(NC=O)C=C1 ZTCQFVRINYOPOH-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- LQNUZADURLCDLV-IDEBNGHGSA-N nitrobenzene Chemical group [O-][N+](=O)[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 LQNUZADURLCDLV-IDEBNGHGSA-N 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000010891 toxic waste Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a synthetic method of p-nitroaniline compounds, and relates to the technical field of organic synthesis. The synthesis method provided by the invention comprises the steps of substituting an amide compound II or an amino acid compound I for a nitrobenzene compound III in an oxygen-containing atmosphere at 20-100 ℃ and a solvent environment under an alkali accelerator, and then extracting and purifying to obtain the corresponding paranitroaniline compound. The synthesis method provided by the invention is simple, does not need to use an expensive transition metal catalyst, has mild reaction conditions, has the effects of environmental protection and low cost, and is favorable for large-scale synthesis and application of the p-nitroaniline compound.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing a p-nitroaniline compound.
Background
Amino acids or amides substituted p-nitrobenzene compounds are important structural units of many natural products and medicines, and meanwhile, the compounds can be used for preparing ligands, artificial dyes, electronic materials and optical materials, so that various methods for synthesizing amino acids or amides substituted p-nitrobenzene compounds are developed. Among these, the most classical methods are the ammonolysis of p-nitrochlorobenzene and the nitrohydrolysis of acetanilide under copper catalysis.
For example, under the catalysis system of Pd 2(dba)3 and Al 2O3, after the indolyline-2-carboxylic acid reacts with the p-bromonitrobenzene under the microwave condition, the yield of the product is 53%; after 1-trifluoromethanesulfonyl-4-nitronaphthalene reacts with L-alanine methyl ester derivative under the catalysis system of Pd 2(dba)3 and cesium carbonate, the product yield is 43-79%; the reaction mechanism of the catalytic reaction is that a transition metal catalyst is inserted into a C-X bond in aryl halogen under the high temperature condition, then amide is added to the transition metal, and the transition metal leaves to carry out elimination reaction, so that a target product is generated.
The disadvantages of these methods are the need for transition metal catalysis, the formation of heterogeneous byproducts at other sites or the use of reaction conditions such as nitric acid which are inconvenient for subsequent processing, and the adverse atomic economy and environmental protection requirements. Although transition metal catalyzed reactions of N-substituted p-nitroanilides are widely used, there are a number of disadvantages such as: 1) The risk of nitration is high, and explosion is easy to cause; 2) Requiring more severe conditions (high temperature and high pressure or nitric acid oxidation); 3) Heavy metal pollution is generated, especially when synthesizing compounds with high requirements on heavy metal content; 4) The selectivity of the reaction product sites is a problem. The reaction without the catalysis of transition metal is more environment-friendly and economical. Transition metal catalysts, while effective in some reactions, are generally expensive and may produce toxic waste during use, causing environmental pollution. Therefore, it is necessary to develop a green synthesis method.
Disclosure of Invention
The invention aims to provide a synthesis method of paranitroaniline compounds, which is simple, does not need to use an expensive transition metal catalyst, has mild reaction conditions, has the effects of environmental protection and low cost, and is beneficial to large-scale synthesis and application of the paranitroaniline compounds.
In a first aspect, the invention provides a method for synthesizing paranitroaniline compounds, which comprises the steps of reacting an amide compound II with a nitrobenzene compound III for 1-8 hours in an oxygen-containing atmosphere at 20-100 ℃ and a solvent environment under an alkali accelerator, and purifying and separating to obtain a paranitroaniline compound V;
；
Wherein, R 4、R5 is hydrogen, alkyl of C 1-C5 independently, R 6 is hydrogen, aliphatic of C 1-C40, aromatic of C 4-C60, alkoxy, trifluoromethoxy, trifluoromethyl, nitro, cyano, alkyl, hydroxy, carboxyl, aldehyde, carbonyl, ester, amino, sulfo, amide or halogen.
Optionally, the alkali promoter comprises at least one of potassium tert-butoxide, sodium tert-butoxide, potassium hydroxide, sodium hydroxide, potassium carbonate, and lithium tert-butoxide.
Optionally, the solvent comprises at least one of toluene, tetrahydrofuran, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, 1, 4-dioxane, diethyl ether, and carbon tetrachloride.
Optionally, the aliphatic group of C 1-C40 includes at least one of methyl, ethyl, propyl, isopropyl, butyl, benzyl.
Optionally, the aromatic group of C 4-C60 includes at least one of pyridine derivative group, phenyl group, substituted phenyl group, 1-naphthyl group, 2-naphthyl group.
Optionally, the halogen includes at least one of fluorine, chlorine, bromine, iodine.
Optionally, the oxygen volume fraction in the oxygen-containing atmosphere is 20-100%.
Optionally, the oxygen-containing atmosphere includes at least one of an oxygen atmosphere and an air atmosphere.
Optionally, the molar ratio of the amide compound II to the nitrobenzene compound III is 1: (1-10).
Optionally, the molar ratio of the alkali promoter to the reactant is 6:10, wherein the reactant comprises an amide compound II and a nitrobenzene compound III.
Alternatively, the molar concentration of the reactant in the solvent is 0.01-100mol/L, wherein the reactant comprises an amide compound II and a nitrobenzene compound III.
Optionally, the process of purifying and separating the p-nitroaniline compound V comprises the following steps: extracting the reaction system after the reaction is finished by using an extracting agent, separating to obtain an organic phase, and performing column chromatography separation on the organic phase to obtain the paranitroaniline compound V.
Optionally, the structural formula of the amide compound II comprises at least one of the following chemical formulas II-1 to II-3:
。
In the second aspect, the synthesis method of the paranitroaniline compound provided by the invention comprises the steps of reacting an amino acid compound I with a nitrobenzene compound III for 1-8 hours in an oxygen-containing atmosphere at 20-100 ℃ and a solvent environment under an alkali accelerator, and purifying and separating to obtain the paranitroaniline compound IV;
；
wherein, R 1、R2、R3 is hydrogen, alkyl of C 1-C5 independently, R 6 is hydrogen, aliphatic of C 1-C40, aromatic of C 4-C60, alkoxy, trifluoromethoxy, trifluoromethyl, nitro, cyano, alkyl, hydroxy, carboxyl, aldehyde, carbonyl, ester, amino, sulfo, amide or halogen.
Optionally, the alkali promoter comprises at least one of potassium tert-butoxide, sodium tert-butoxide, potassium hydroxide, sodium hydroxide, potassium carbonate, and lithium tert-butoxide.
Optionally, the solvent comprises at least one of toluene, tetrahydrofuran, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, 1, 4-dioxane, diethyl ether, and carbon tetrachloride.
Optionally, the aliphatic group of C 1-C40 includes at least one of methyl, ethyl, propyl, isopropyl, butyl, benzyl.
Optionally, the aromatic group of C 4-C60 includes at least one of pyridine derivative group, phenyl group, substituted phenyl group, 1-naphthyl group, 2-naphthyl group.
Optionally, the halogen includes at least one of fluorine, chlorine, bromine, iodine.
Optionally, the oxygen volume fraction in the oxygen-containing atmosphere is 20-100%.
Optionally, the oxygen-containing atmosphere includes at least one of an oxygen atmosphere and an air atmosphere.
Optionally, the molar ratio of the amino acid compound I to the nitrobenzene compound III is 1: (1-10).
Optionally, the molar ratio of the base promoter to the reactants is 6:10, wherein the reactants comprise amino acid compound i and nitrobenzene compound iii.
Alternatively, the molar concentration of the reactants in the solvent is 0.01-100mol/L, wherein the reactants comprise amino acid compound I and nitrobenzene compound III.
Optionally, the process of purifying and separating the p-nitroaniline compound IV comprises the following steps: extracting the reaction system after the reaction is finished by using an extracting agent, separating to obtain an organic phase, and performing column chromatography separation on the organic phase to obtain the paranitroaniline compound IV.
Optionally, the structural formula of the amino acid compound I comprises at least one of the following chemical formulas I-1 to I-2:
。
Drawings
FIG. 1 is a nuclear magnetic resonance spectrum of a paranitroaniline compound prepared in example 1 of the present invention;
FIG. 2 is a nuclear magnetic resonance spectrum of the p-nitroaniline compound prepared in example 1 of the present invention;
FIG. 3 is a nuclear magnetic resonance spectrum of the p-nitroaniline compound prepared in example 2 of the present invention;
FIG. 4 is a nuclear magnetic resonance spectrum of the p-nitroaniline compound prepared in example 2 of the present invention;
FIG. 5 is a nuclear magnetic resonance spectrum of the p-nitroaniline compound prepared in example 8 of the present invention;
FIG. 6 is a nuclear magnetic resonance spectrum of the p-nitroaniline compound prepared in example 8 of the present invention;
FIG. 7 is a reaction equation of amide compound II and nitrobenzene compound III provided by the invention.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention. Unless otherwise defined, technical or scientific terms used herein should be given the ordinary meaning as understood by one of ordinary skill in the art to which this invention belongs. As used herein, the word "comprising" and the like means that elements or items preceding the word are included in the element or item listed after the word and equivalents thereof without precluding other elements or items.
The embodiment of the invention provides a method for synthesizing a paranitroaniline compound, which comprises the steps of reacting an amide compound II with a nitrobenzene compound III for 1-8 hours in an oxygen-containing atmosphere at 20-100 ℃ and a solvent environment under an alkali accelerator, and purifying and separating to obtain the paranitroaniline compound V.
In practice, the method without transition metal catalysis is adopted to catalyze the reaction of the amide compound and the nitrobenzene compound to generate the paranitroaniline compound, which is more environment-friendly, has lower economic cost and is beneficial to the application of the paranitroaniline compound in organic ligands, artificial dyes, electronic materials and optical materials.
Specifically, referring to fig. 7, when the amide compound ii is reacted with the nitrobenzene compound iii, the reaction equation is as follows:
；
Wherein R 4、R5 is independently hydrogen, alkyl of C 1-C5, R 6 is hydrogen, aliphatic of C 1-C40, aromatic of C 4-C60, alkoxy, trifluoromethoxy, trifluoromethyl, nitro, cyano, alkyl, hydroxy, carboxyl, aldehyde, carbonyl, ester, amino, sulfo, amide or halogen. In practice, R 4 and R 5 may also be cyclic substituents or chain substituents.
Specifically, the aliphatic group of C 1-C40 includes at least one of methyl, ethyl, propyl, isopropyl, butyl, and benzyl, the aromatic group of C 4-C60 includes at least one of pyridine derivative group, phenyl, substituted phenyl, 1-naphthyl, and 2-naphthyl, and the halogen includes at least one of fluorine, chlorine, bromine, and iodine.
In some embodiments, when the amide compound ii reacts with the nitrobenzene compound iii, the nitrobenzene compound iii may be excessively disposed, which is advantageous for the forward reaction, and improves the conversion rate of the amide compound ii and the yield of the p-nitroaniline compound v. Specifically, the molar ratio of the amide compound II to the nitrobenzene compound III in the reaction can be 1: (1-10).
In fact, under the action of the alkali accelerator, the amide compound II loses an H proton and is converted into N negative ions, then the N negative ions are oxidized into N free radicals by oxygen in an oxygen-containing atmosphere, and the N free radicals have high reactivity and attack C-H bonds at the para position of the nitrobenzene compound III, so that a coupling reaction occurs to form the stable paranitroaniline compound.
In some embodiments, the base promoter may be at least one of potassium tert-butoxide, sodium tert-butoxide, potassium hydroxide, sodium hydroxide, potassium carbonate, lithium tert-butoxide. In practice, when the amide compound II reacts with the nitrobenzene compound III under the alkali accelerator, the molar ratio of the alkali accelerator to the reactant (the amide compound II and the nitrobenzene compound III) is 6:10, which is favorable for the alkali accelerator to fully contact with the amide compound II and the nitrobenzene compound III in a reaction system, thereby improving the reaction efficiency.
In some embodiments, the oxygen-containing atmosphere may be a mixed atmosphere with an oxygen volume fraction of 20-100%, which actually helps to oxidize the N negative ions of the amide compound ii after losing one H proton along with the increase of the oxygen content in the oxygen-containing atmosphere, thereby helping to improve the reaction efficiency. Specifically, the oxygen-containing atmosphere may be an air atmosphere or an oxygen atmosphere.
In some embodiments, the solvent environment may be at least one of toluene, tetrahydrofuran, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, 1, 4-dioxane, diethyl ether, carbon tetrachloride. In practice, the solvent environment may be selected from organic solvents commonly used in the art, so as to be capable of completely dissolving the reactants and the target product without chemical reaction.
Specifically, when the amide compound II reacts with the nitrobenzene compound III in a solvent environment, the molar concentration of the amide compound II and the nitrobenzene compound III after being mixed in the solvent is 0.01-100mol/L.
In some embodiments, amide II may specifically include at least one of the following formulas II-1 to II-3:
。
In practice, the process of purifying and separating the p-nitroaniline compound V comprises the following steps: extracting the reaction system after the reaction is finished by using an extracting agent, separating to obtain an organic phase, and performing column chromatography separation on the organic phase to obtain the paranitroaniline compound V. In practice, when the extractant is used for extraction, the target product paranitroaniline compound V can be transferred into the extractant, so that the organic phase is separated and obtained, and after column chromatography purification is carried out, the product purity of the paranitroaniline compound V is improved. Specifically, the extractant may be ethyl acetate.
The embodiment of the invention also provides a synthesis method of the paranitroaniline compound, wherein the amide compound II used in any embodiment is replaced by the amino acid compound I, and the paranitroaniline compound IV is obtained by purifying and separating after reacting with the nitrobenzene compound III for 1-8 hours.
Specifically, when the amino acid compound I is reacted with the nitrobenzene compound III, the reaction equation is shown as follows:
；
wherein, R 1、R2、R3 is hydrogen, alkyl of C 1-C5 independently, R 6 is hydrogen, aliphatic of C 1-C40, aromatic of C 4-C60, alkoxy, trifluoromethoxy, trifluoromethyl, nitro, cyano, alkyl, hydroxy, carboxyl, aldehyde, carbonyl, ester, amino, sulfo, amide or halogen.
In some embodiments, amino acid compound I may specifically include at least one of the following formulas I-1 through I-2:
。
In practice, the process of purifying and separating the p-nitroaniline compound IV comprises the following steps: extracting the reaction system after the reaction is finished by using an extracting agent, separating to obtain an organic phase, and performing column chromatography separation on the organic phase to obtain the paranitroaniline compound IV. In practice, when the extractant is used for extraction, the target product paranitroaniline compound IV can be transferred into the extractant, so that the organic phase is separated and obtained, and after column chromatography purification is carried out, the product purity of the paranitroaniline compound IV is improved. Specifically, the extractant may be ethyl acetate.
Example 1
The present example 1 provides a method for synthesizing p-nitroaniline compounds substituted with amino acid compound i, comprising the steps of:
S1, adding 0.2mmol of glycine I-1 and 0.8mmol of nitrobenzene III-1 into a reaction container, uniformly mixing, adding 0.6mmol of potassium tert-butoxide as an alkali accelerator, stirring and mixing, replacing oxygen in the reaction container for three times, adding dimethyl sulfoxide as a solvent environment in an oxygen atmosphere, and stirring and reacting for 3 hours at 50 ℃;
S2, adding water into the reaction system after the reaction is finished for quenching, extracting the reaction system by using ethyl acetate as an extraction solvent, and separating an organic phase obtained by extraction by column chromatography (V Petroleum ether ：V Acetic acid ethyl ester =2:1) to obtain 33.33g of 4-nitrohippuric acid IV-1, wherein the calculated yield is 85%.
Specifically, during the synthesis of example 1, the following reactions occur:
。
After the 4-nitrohippuric acid synthesized in the example 1 is subjected to nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum characterization, the characteristics are shown in fig. 1 and fig. 2, and the characterization data are as follows ：1H NMR (400 MHz, DMSO) δ 12.80 (s, 1H), 8.00 (d, J = 9.20 Hz, 2H), 7.45 (t, J = 6.20 Hz, 1H), 6.66 (d, J = 9.20 Hz, 2H), 3.98 (d J = 6.2 Hz, 2H).13C NMR (101 MHz, DMSO) δ 171.4, 154.3, 136.3, 126.0, 111.2 .
Examples 2 to 4
The present examples 2 to 4 respectively provide a synthesis method of p-nitroaniline compounds substituted with amino acid compound i, which is different from example 1 in the kind, reaction temperature and reaction duration of amino acid compound i.
Specifically, the structural formula of the amino acid compound i, the structural formula of the nitrobenzene compound iii, the structural formula of the objective product, the reaction temperature, the reaction time period, and the yield of the objective product used in the synthesis methods in examples 1 to 4 are shown in table 1 below.
TABLE 1
，
Example 5
The embodiment 5 provides a synthesis method of p-nitroaniline compound substituted by amide compound II, comprising the following steps:
s1, adding 0.2mmol of N-methylformamide II-1 and 0.8mmol of nitrobenzene III-1 into a reaction vessel, uniformly mixing, adding 0.6mmol of potassium tert-butoxide as an alkali accelerator, stirring and mixing, replacing oxygen in the reaction vessel for three times, adding dimethyl sulfoxide as a solvent environment in an oxygen atmosphere, and stirring and reacting for 3 hours at 50 ℃;
S2, adding water into the reaction system after the reaction is finished for quenching, extracting the reaction system by using ethyl acetate as an extraction solvent, and separating an organic phase obtained by extraction by column chromatography (V Petroleum ether ：V Acetic acid ethyl ester =2:1) to obtain 29.53g N- (4-nitrophenyl) formamide V-1, wherein the calculated yield is 82%.
Specifically, during the synthesis of example 5, the following reactions occurred:
。
Examples 6 to 8
The present examples 6 to 8 respectively provide a method for synthesizing a p-nitroaniline compound substituted by an amide compound II, which is different from example 5 in the kind, reaction temperature and reaction duration of the amide compound II.
Specifically, the structural formula of the amide compound II, the structural formula of the nitrobenzene compound III, the structural formula of the objective product, the reaction temperature, the reaction time period and the yield of the objective product used in the synthesis methods of examples 5 to 8 are shown in Table 2 below.
TABLE 2
，
While embodiments of the present invention have been described in detail hereinabove, it will be apparent to those skilled in the art that various modifications and variations can be made to these embodiments. It is to be understood that such modifications and variations are within the scope and spirit of the present invention as set forth in the following claims. Moreover, the invention described herein is capable of other embodiments and of being practiced or of being carried out in various ways.
Claims (8)
1. A synthetic method of p-nitroaniline compounds is characterized in that in an oxygen-containing atmosphere and a solvent environment at 20-100 ℃, amide compounds II react with nitrobenzene compounds III for 1-8 hours under the condition of an alkali accelerator, and then p-nitroaniline compounds V are obtained by purification and separation;
；
Wherein, R 4、R5 is hydrogen, alkyl of C 1-C5 independently, R 6 is hydrogen, aliphatic of C 1-C40, aromatic of C 4-C60, alkoxy, trifluoromethoxy, trifluoromethyl, nitro, cyano, alkyl, hydroxy, carboxyl, aldehyde, carbonyl, ester, amino, sulfo, amide or halogen.
2. The method of synthesis according to claim 1, wherein the alkali promoter comprises at least one of potassium tert-butoxide, sodium tert-butoxide, potassium hydroxide, sodium hydroxide, potassium carbonate, lithium tert-butoxide;
And/or the solvent comprises at least one of toluene, tetrahydrofuran, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, 1, 4-dioxane, diethyl ether and carbon tetrachloride;
And/or the aliphatic group of C 1-C40 comprises at least one of methyl, ethyl, propyl, isopropyl, butyl, benzyl;
And/or the aromatic group of C 4-C60 comprises at least one of pyridine derivative group, phenyl group, substituted phenyl group, 1-naphthyl group and 2-naphthyl group;
and/or, the halogen comprises at least one of fluorine, chlorine, bromine and iodine;
and/or the oxygen volume fraction in the oxygen-containing atmosphere is 20-100%;
And/or the oxygen-containing atmosphere comprises at least one of an oxygen atmosphere and an air atmosphere.
3. The synthesis method according to claim 1, wherein the molar ratio of the amide compound II to the nitrobenzene compound III is 1: (1-10);
And/or the molar ratio of the alkali accelerator to the reactant is 6:10, wherein the reactant comprises an amide compound II and a nitrobenzene compound III;
and/or the molar concentration of the reactant in the solvent is 0.01-100mol/L, wherein the reactant comprises an amide compound II and a nitrobenzene compound III.
4. The synthesis method according to claim 1, wherein the process of purifying and separating the p-nitroaniline compound v comprises: extracting the reaction system after the reaction is finished by using an extracting agent, separating to obtain an organic phase, and performing column chromatography separation on the organic phase to obtain the paranitroaniline compound V.
5. The synthetic method according to claim 1, wherein the structural formula of the amide compound ii includes at least one of the following chemical formulas ii-1 to ii-3:
。
6. a method for synthesizing a paranitroaniline compound, which is characterized in that an amide compound II in the method is replaced by an amino acid compound I, and the amino acid compound I and the nitrobenzene compound III react for 1-8 hours, and then the paranitroaniline compound IV is obtained by purification and separation;
；
wherein, R 1、R2、R3 is hydrogen, alkyl of C 1-C5 independently, R 6 is hydrogen, aliphatic of C 1-C40, aromatic of C 4-C60, alkoxy, trifluoromethoxy, trifluoromethyl, nitro, cyano, alkyl, hydroxy, carboxyl, aldehyde, carbonyl, ester, amino, sulfo, amide or halogen.
7. The synthetic method of claim 6 wherein the structural formula of amino acid compound i comprises at least one of the following formulas i-1 to i-2:
。
8. The synthesis method according to claim 6, wherein the process of purifying and separating the p-nitroaniline compound IV comprises the steps of: extracting the reaction system after the reaction is finished by using an extracting agent, separating to obtain an organic phase, and performing column chromatography separation on the organic phase to obtain the paranitroaniline compound IV.
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