CN103664625A - 2,3,4,6-tetrasubstituted phenol derivative and preparation method thereof - Google Patents
2,3,4,6-tetrasubstituted phenol derivative and preparation method thereof Download PDFInfo
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- CN103664625A CN103664625A CN201310674886.3A CN201310674886A CN103664625A CN 103664625 A CN103664625 A CN 103664625A CN 201310674886 A CN201310674886 A CN 201310674886A CN 103664625 A CN103664625 A CN 103664625A
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- -1 2,3,4,6-tetrasubstituted phenol Chemical class 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- 239000003513 alkali Substances 0.000 claims abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 46
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 35
- 150000002505 iron Chemical class 0.000 claims description 26
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical group [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 15
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 14
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 11
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 9
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 7
- 150000002989 phenols Chemical class 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims 2
- 239000002585 base Substances 0.000 claims 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 21
- 150000003839 salts Chemical class 0.000 abstract description 9
- 230000008092 positive effect Effects 0.000 abstract 1
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 44
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 32
- 150000007529 inorganic bases Chemical class 0.000 description 31
- 239000002904 solvent Substances 0.000 description 20
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 11
- 229910001914 chlorine tetroxide Inorganic materials 0.000 description 9
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 238000004896 high resolution mass spectrometry Methods 0.000 description 8
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 8
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- POSICDHOUBKJKP-UHFFFAOYSA-N prop-2-enoxybenzene Chemical group C=CCOC1=CC=CC=C1 POSICDHOUBKJKP-UHFFFAOYSA-N 0.000 description 3
- 229910052703 rhodium Inorganic materials 0.000 description 3
- 239000010948 rhodium Substances 0.000 description 3
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- 239000013064 chemical raw material Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 0 Cc1c(-c2ccccc2)c(O)c(*)cc1C=O Chemical compound Cc1c(-c2ccccc2)c(O)c(*)cc1C=O 0.000 description 1
- GYCKQBWUSACYIF-UHFFFAOYSA-N Ethyl salicylate Chemical compound CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
- 241001647769 Mirza Species 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- DGCTVLNZTFDPDJ-UHFFFAOYSA-N heptane-3,5-dione Chemical compound CCC(=O)CC(=O)CC DGCTVLNZTFDPDJ-UHFFFAOYSA-N 0.000 description 1
- 159000000014 iron salts Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
- C07C69/94—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring of polycyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a 2,3,4,6-tetrasubstituted phenol derivative, the structure of which is as shown in formula (I). The invention further discloses a preparation method of 2,3,4,6-tetrasubstituted phenol derivative, at room temperature and under the protection of nitrogen, the 2,3,4,6-tetrasubstituted phenol derivative is synthesized in the presence of alkali by using an eneyne ester compound and a 1,3-dicarbonyl compound as raw materials and using ferric salt as a catalyst. The preparation method provided by the invention has the positive effects of having low cost and mild reaction conditions, being environment-friendly, and the like.
Description
Technical Field
The invention belongs to the technical field of organic compounds and synthesis, and particularly relates to a 2,3,4, 6-tetrasubstituted phenol derivative and a synthesis preparation method thereof.
Background
Polysubstituted phenol derivatives (phenols) are an important class of aromatic compounds. The compounds are widely applied to the aspects of plastics, medicines, pesticides, perfumes, dyes, coatings and the like, and can also be used as bactericides, preservatives and the like. The synthesis of 2,3,4, 6-tetra-substituted phenol derivatives has been reported in the literature, but such reports are still few, expensive metal catalysts such as palladium, rhodium and the like are used, and the reported method is limited in that: (1) expensive metal reagents are adopted, so that the reaction cost is increased; (2) the metals such as palladium, rhodium and the like have certain toxicity and are easy to cause environmental pollution. Methods for synthesizing 2,3,4, 6-tetrasubstituted phenol derivatives by using metal catalysis such as palladium, rhodium, titanium and the like have been reported, for example: document (1) divier, c.; aiain, d.tetrahedron lett.1997, 38, 1397-; van t.h.n.; ehsan u.; sunanda l.; helmar G.; peter l.j.org.chem.2004, 69, 9128-; simone, l.; helmut, r.; ake, s.; christine, f.; peter, l.synthesis2009, 13, 2236-; abdolmjid, r.; olumide, f.; ibrar h.; mirza, a.y.; M.L.; stefanie, r.; helmut, r.; christine, f.; peter, l.org.biomol.chem.2009, 7, 2182-2186.
The preparation method of the 2,3,4, 6-tetrasubstituted phenol derivative in the prior art has the following defects: expensive metal reagents are adopted, so that the reaction cost is increased; and because the adopted metal has certain toxicity, the environment pollution is easy to cause.
Disclosure of Invention
The invention aims to provide a 2,3,4, 6-tetrasubstituted phenol derivative.
The structure of the 2,3,4, 6-tetra-substituted phenol derivative provided by the invention is shown as the following formula (I):
wherein R is1＝C1-20Alkyl, ethoxy of (a); r2Is C1-20Alkyl groups of (a); r3Is an electron-withdrawing group or an electron-donating group; wherein, the electron-withdrawing group can be halogen, and the electron-donating group can be alkyl or alkoxy.
The invention also aims to provide a method for synthesizing the 2,3,4, 6-tetra-substituted phenol derivative, which is iron-catalyzed, low in cost, mild in reaction condition and environment-friendly.
The preparation method of the 2,3,4, 6-tetrasubstituted phenol derivative adopts the following technical scheme: taking an eneyne ether compound and a 1, 3-dicarbonyl compound as raw materials to carry out cyclization reaction, and taking iron salt as a catalyst and cesium carbonate as alkali to synthesize the 2,3,4, 6-tetra-substituted phenol derivative. The method has the advantages of simple and easily obtained raw materials, simple and convenient post-treatment, cheap catalyst, good yield and environmental friendliness. The method is shown as the following formula (II):
wherein R is1＝C1-20Alkyl, ethoxy of (a); r2Is C1-20Alkyl groups of (a); r3Is an electron-withdrawing group or an electron-donating group; wherein, the electron-withdrawing group can be halogen, and the electron-donating group can be alkyl or alkoxy.
The invention provides a method for synthesizing 2,3,4, 6-tetrasubstituted phenol derivatives, which comprises the following steps of heating an eneyne ether compound and a 1, 3-dicarbonyl compound in a proper solvent in the presence of a catalyst iron salt and an inorganic base at room temperature under the protection of nitrogen, reacting for 1-16 hours at 35 ℃, separating and purifying to obtain polysubstituted phenol derivatives, wherein the synthesis method comprises the following steps: 1, 3-dicarbonyl compound: inorganic base: the molar ratio of the iron salt is 1.0: 2.0: 2.0: 0.1, yield 50-84%, the iron salt is Fe (ClO)4)39H2O、Fe(SO4)3、FeCl3Etc., the inorganic base is Cs2CO3The solvent may be N, N-Dimethylformamide (DMF).
Compared with the prior art, the invention has the following advantages:
(1) the raw material eneyne ether compound is simple and convenient to synthesize, and the 1, 3-dicarbonyl compound is a common chemical raw material.
(2) The used iron salt is non-toxic, environment-friendly and low in price.
(3) The adopted inorganic base is a common chemical raw material and is easy to obtain.
(4) The reaction condition is mild, the compound can be obtained with good yield, and the product is stable.
Detailed Description
The present invention will be described in further detail with reference to the following specific examples. The procedures, conditions, reagents, experimental methods and the like for carrying out the present invention are general knowledge and common general knowledge in the art except for the contents specifically mentioned below, and the present invention is not particularly limited.
The invention provides a synthesis method of 2,3,4, 6-tetra-substituted phenol derivatives, which comprises the following steps of heating an eneyne ether compound and a 1, 3-dicarbonyl compound in a proper solvent in the presence of a catalyst iron salt and an inorganic base at room temperature under the protection of nitrogen, reacting for 1-16 hours at the temperature of 35 ℃, separating and purifying to obtain the polysubstituted phenol derivatives, wherein the eneyne ether comprises the following components in parts by weight: 1, 3-dicarbonyl compound: inorganic base: the molar ratio of the iron salt is 1.0: 2.0: 2.0: 0.1, and the yield is 48-84%. In the present process, suitable iron salts include Fe (ClO)4)39H2O、Fe(SO4)3、FeCl3Etc., suitable inorganic bases are Cs2CO3A suitable solvent is N, N-Dimethylformamide (DMF).
The reaction formula of the preparation method of the invention is as follows:
wherein R is1＝C1-20Alkyl, ethoxy of (a); r2Is C1-20Alkyl groups of (a); r3Is electron withdrawing group (halogen) and electron donating group (alkyl and alkoxy).
The technical solution of the present invention is further illustrated by the following examples. All examples were carried out according to the synthesis method described above, the technical parameters listed being cited only for practical reference. The target compound can be prepared under the conditions mentioned in the invention, and the yield reaches 50-84%.
Example 1: 2-phenyl-3-methyl-4-acetyl-6-carboximidoylphenol
Synthesis of (2)
The acetylene ether, the 1, 3-dicarbonyl compound, the inorganic base, the iron salt and the solvent are respectively selected from (E) -Ethyl2- (phenoxymethyl ethylene) -4-phenylbut-3-ynoate, acetylacetone and Cs2CO3、Fe(ClO4)39H2O, N, N-dimethylformamide, the dosage of the raw materials is 0.3mmol of eneyne ether alkyne, 0.6mmol of acetylacetone, 0.6mmol of inorganic base, 3ml of solvent and 0.03mmol of ferric salt, the reaction is carried out for 1 hour at 35 ℃, and the reaction is carried out on eneyne ether: acetylacetone: inorganic base: iron salt 1.0: 2.0: 2.0: 0.1, obtaining the target product, yellow solid and yield 84%.
1H NMR(400MHZ，CDCl3，Me4Si)δ1.36(t，3H)，2.19(s，3H)，2.54(s，3H)，4.37(q，2H)，7.12(d，J＝7.2Hz，2H)，7.30-7.40(m，3H)，8.19(s，1H)，11.34(s，1H)；13C NMR(100.6MHZ，CDCl3，Me4Si)13.88, 19.18, 29.37, 61.77, 109.56, 127.76, 128.67, 130.02, 130.60, 131.05, 132.86, 136.16, 145.68, 161.76, 170.20, 200.75 high resolution Mass Spectrometry (ESI) C18H19O4(M + H), theoretical value: 299.1283, found: 299.1266.
example 2: 2-phenyl-3-ethyl-4-propionyl-6-carboxylic acid ethyl ester phenol
Synthesis of (2)
The acetylene ether, the 1, 3-dicarbonyl compound, the inorganic base, the iron salt and the solvent are respectively selected from (E) -Ethyl2- (phenoxymethyl ethylene) -4-phenonylbut-3-ynoate, 3, 5-heptanedione and Cs2CO3、Fe(ClO4)39H2O, N, N-dimethylformamide, the dosage of the raw materials is 0.3mmol of eneyne ether, 0.6mmol of acetylacetone, 0.6mmol of inorganic base, 3ml of solvent and 0.03mmol of ferric salt, the reaction is carried out for 5 hours at 35 ℃, and the reaction is carried out on the eneyne ether: acetylacetone: inorganic base: iron salt 1.0: 2.0: 2.0: 0.1, obtaining a target product, namely a light yellow liquid with the yield of 72 percent.
1H NMR(400MHZ，CDCl3，Me4Si)δ0.95(t，3H)，1.23(t，3H)，1.44(t，3H)，2.68(q，2H)，2.97(q，2H)，4.44(q，2H)，7.22(d，J＝7.2Hz，2H)，7.38-7.48(m，3H)，8.19(s，1H)，11.34(s，1H).13C NMR(100.6MHZ，CDCl3，Me4Si) delta 8.21, 13.90, 15.17, 23.75, 34.82, 61.70, 109.54, 127.70, 128.51, 130.03, 130.20, 130.48, 132.42, 136.00, 151.26, 161.59, 170.17, 204.33 high resolution mass spectrometry (ESI) C20H23O4(M + H), theoretical value: 327.1596, found: 327.1596.
example 3: 2- (4-methyl) phenyl-3-methyl-4-acetyl-6-carboximidoylphenol
Synthesis of (2)
The enynol ether, the 1, 3-dicarbonyl compound, the inorganic base, the ferric salt and the solvent are respectively selected from (E) -Ethyl2- (phenoxymethyl ethylene) -4-p-tollbut-3-ynoate, acetylacetone and Cs2CO3、Fe(ClO4)39H2O, N, N-dimethylformamide, the dosage of the raw material is the eneyne ether 0.3mmol, acetylacetone 0.6mmol, inorganic base 0.6mmol, solvent 3ml, iron salt 0.03mmol, reaction at 35 ℃ for 3 hours, enynylether: acetylacetone: inorganic base: iron salt 1.0: 2.0: 2.0: 0.1, obtaining the target product as light yellow solid with the yield of 68 percent.
1H NMR(400MHZ，CDCl3，Me4Si)δ1.36(t，3H)，2.20(s，3H)，2.32(s，3H)，2.53(s，3H)，4.37(q，2H)，7.00(d，J＝7.6Hz，2H)，7.19d，J＝7.6Hz，2H)，，8.18(s，1H)，11.34(s，1H).13C NMR(100.6MHZ，CDCl3，Me4Si) δ 13.88, 19.19, 20.97, 29.35, 61.73, 109.46, 129.44, 129.83, 130.55, 130.92, 132.84, 133.01, 137.45, 145.77, 161.85, 170.22, 200.77 high resolution mass spectrometry (ESI) C19H21O4(M + H), theoretical value: 313.1440, found: 313.1440.
example 4: 2- (4-methoxy) phenyl-3-methyl-4-acetyl-6-carboximidoylphenol
Synthesis of (2)
The acetylene ether, 1, 3-dicarbonyl compound, inorganic base, iron salt and solvent are (E) -Ethyl4- (4-methoxyphenyl) -2- (phenoxymethyl) but-3-ynoate, acetylacetone and Cs respectively2CO3、Fe(ClO4)39H2O, N, N-dimethylformamide, the dosage of the raw materials is 0.3mmol of eneyne ether, 0.6mmol of acetylacetone, 0.6mmol of inorganic base, 3ml of solvent and 0.03mmol of ferric salt, the reaction is carried out for 2 hours at 35 ℃, and the reaction is carried out on the eneyne ether: acetylacetone: inorganic base: iron salt 1.0: 2.0: 2.0: 0.1, obtaining the target product as light yellow solid with the yield of 61%.
1H NMR(400MHZ，CDCl3，Me4Si)δ1.36(t，3H)，2.20(s，3H)，2.53(s，3H)，3.76(s，2H)，4.37(q，2H)，6.91(d，J＝8.0Hz，2H)，7.04(d，J＝8.4Hz，2H)，8.17(s，1H)，11.35(s，1H). 13C NMR(100.6MHZ，CDCl3，Me4Si) delta 13.86, 19.20, 29.33, 55.02, 61.73, 109.47, 114.07, 128.08, 130.61, 130.85, 131.14, 132.50, 145.95, 159.27, 162.00, 170.24, 200.77 high resolution mass spectrometry (ESI) C19H21O5(M + H), theoretical value: 329.1389, found: 329.1387.
example 5: 2- (4-chloro) phenyl-3-methyl-4-acetyl-6-carboximidoylphenolSynthesis of (2)
The acetylene ether, the 1, 3-dicarbonyl compound, the inorganic base, the iron salt and the solvent are respectively selected from (E) -Ethyl4- (4-chlorophenylene) -2- (phenoxymethyl) but-3-ynoate, acetylacetone and Cs2CO3、Fe(ClO4)39H2O, N, N-dimethylformamide, the dosage of the raw materials is 0.3mmol of eneyne ether, 0.6mmol of acetylacetone, 0.6mmol of inorganic base, 3ml of solvent and 0.03mmol of ferric salt, the reaction is carried out for 3 hours at 35 ℃, and the reaction is carried out on the eneyne ether: acetylacetone: inorganic base: iron salt 1.0: 2.0: 2.0: 0.1, obtaining the target product, namely a light yellow solid with the yield of 50 percent.
1H NMR(400MHZ，CDCl3，Me4Si)δ1.37(t，3H)，2.19(s，3H)，2.54(s，3H)，4.38(q，2H)，7.05-7.07(m，2H)，7.35-7.37(m，2H)，8.19(s，1H)，11.37(s，1H)13C NMR(100.6MHZ，CDCl3，Me4Si)δ13.90，19.18，29.36，61.89，109.69，128.98，130.67，131.28，131.56, 131.61, 133.86, 134.55, 145.64, 161.66, 170.15, 200.63 high resolution Mass Spectrometry (ESI) C18H18ClO4(M + H), theoretical value: 333.0894, found: 333.0891.
example 6: 2-phenyl-3-methyl-4, 6-dicarboxylic acid carbethoxyphenol
Synthesis of (2)
The acetylene ether, the 1, 3-dicarbonyl compound, the inorganic base, the iron salt and the solvent are respectively selected from (E) -Ethyl4- (4-methoxyphenyl) -2- (phenoxymethyl) but-3-ynoate, Ethyl acetoacetate and Cs2CO3、Fe(ClO4)39H2O, N, N-dimethylformamide, the dosage of the raw materials is 0.3mmol of eneyne ether, 0.6mmol of acetylacetone, 0.6mmol of inorganic base, 3ml of solvent and 0.03mmol of ferric salt, the reaction is carried out for 16 hours at 35 ℃, and the reaction is carried out on the eneyne ether: acetylacetone: inorganic base: iron salt 1.0: 2.0: 2.0: 0.1, obtaining the target product, namely a light yellow solid with the yield of 51 percent.
1H NMR(400MHZ，CDCl3，Me4Si)δ1.35(m，6H)，2.26(s，3H)，4.29(q，2H)，2.4.37(q，2H)，7.13(d，J＝6.8Hz，2H)，7.31-7.40(m，3H)，8.38(s，1H)，11.33(s，1H).13C NMR(100.6MHZ，CDCl3，Me4Si) delta 13.88, 14.03, 19.13, 60.77, 61.70, 110.06, 122.51, 127.73, 128.67, 130.11, 132.27, 132.42, 136.35, 146.61, 161.85, 167.62, 170.39 high resolution mass spectrometry (ESI) C19H21O5(M + H), theoretical value: 329.1389, found: 329.1389.
example 7: 2- (1-naphthyl) -3-methyl-4-acetyl-6-carboximidoylphenolSynthesis of (2)
The acetylene ether, the 1, 3-dicarbonyl compound, the inorganic base, the iron salt and the solvent are respectively selected from (E) -Ethyl4- (4-naphthalen-1-yl) -2- (phenoxymethyl) but-3-ynoate, acetylacetone and Cs2CO3、Fe(ClO4)39H2O, N, N-dimethylformamide, the dosage of the raw materials is 0.3mmol of eneyne ether, 0.6mmol of acetylacetone, 0.6mmol of inorganic base, 3ml of solvent and 0.03mmol of ferric salt, the reaction is carried out for 2 hours at 35 ℃, and the reaction is carried out on the eneyne ether: acetylacetone: inorganic base: iron salt 1.0: 2.0: 2.0: 0.1, obtaining the target product, yellow solid and the yield is 77%.
1H NMR(400MHZ，CDCl3，Me4Si)δ1.34(t，3H)，2.08(s，3H)，2.56(s，3H)，4.35(q，2H)，7.21(d，J＝6.8Hz，1H)，7.27-7.28(m，2H)，7.36-7.38(m，1H)，7.47(t，1H).13C NMR(100.6MHZ，CDCl3，Me4Si) δ 13.88, 18.85, 29.35, 61.80, 109.68, 125.14, 125.75, 126.12, 126.47, 127.62, 128.40, 128.70, 130.58, 130.80, 131.52, 132.06, 133.92, 133.96, 146.89, 162.22, 170.13, 200.64 high resolution mass spectrometry (ESI) C22H21O4(M + H), theoretical value: 349.1440, found: 349.1433.
example 8: 2- (3, 4, 5-trimethoxy) phenyl-3-methyl-4-acetyl-6-carboximidoylphenol
Synthesis of (2)
The acetylene ether, the 1, 3-dicarbonyl compound, the inorganic base, the iron salt and the solvent are respectively selected from (E) -Ethyl2- (phenoxymethyl) -4- (3, 4, 5-trimethoxyphenyl) but-3-ynoate, acetylacetone and Cs2CO3、Fe(ClO4)39H2O, N, N-dimethylformamide, the dosage of the raw materials is 0.3mmol of eneyne ether, 0.6mmol of acetylacetone, 0.6mmol of inorganic base, 3ml of solvent and 0.03mmol of ferric salt, the reaction is carried out for 5 hours at 35 ℃, and the reaction is carried out on the eneyne ether: acetylacetone: inorganic base: iron salt 1.0: 2.0: 2.0: 0.1, obtaining the target product, white solid with the yield of 48 percent.
1H NMR(400MHZ，CDCl3，Me4Si)δ1.46(t，3H)，2.31(s，3H)，2.63(s，3H)，3.85(s，6H)，3.92(s，3H)，4.48(q，2H)，6.42(s，2H)，8.27(s，1H)，11.50(s，1H).13C NMR(100.6MHZ，CDCl3，Me4Si) delta 13.86, 19.14, 29.33, 55.88, 60.70, 61.82, 106.82, 109.53, 130.67, 130.89, 131.57, 132.79, 137.45, 145.84, 153.64, 161.62, 170.18, 200.73 high resolution mass spectrometry (ESI) C21H25O7(M + H), theoretical value: 389.1600, found: 389.1602.
the protection of the present invention is not limited to the above embodiments. Variations and advantages that may occur to those skilled in the art may be incorporated into the invention without departing from the spirit and scope of the inventive concept, and the scope of the appended claims is intended to be protected.
Claims (7)
1. A2, 3,4, 6-tetrasubstituted phenol derivative represented by the following formula (I):
wherein,
R1＝C1-20alkyl or ethoxy of (a);
R2is C1-20Alkyl groups of (a);
R3is an electron withdrawing group or an electron donating group; wherein the electron-withdrawing group is halogen and the electron-donating group is alkyl or alkoxy.
2. A preparation method of a 3,4, 6-tetrasubstituted phenol derivative is characterized in that under the room temperature and the protection of nitrogen, an enyne ether compound and a 1, 3-dicarbonyl compound are used as raw materials, an iron salt is used as a catalyst, and the 2,3,4, 6-tetrasubstituted phenol derivative is synthesized in the presence of alkali; as shown in the following formula (II):
wherein,
R1＝C1-20alkyl or ethoxy of (a);
R2is C1-20Alkyl groups of (a);
R3is an electron withdrawing group or an electron donating group; wherein the electron-withdrawing group is halogen and the electron-donating group is alkyl or alkoxy.
3. The method of claim 2, wherein the method is carried out at 35 ℃.
4. The process according to claim 2, wherein the ratio of the alkenyl ether: 1, 3-dicarbonyl compounds: alkali: the molar ratio of the iron salt is 1.0: 2.0: 2.0: 0.1.
5. the method of claim 2, wherein the base is Cs2CO3。
6. The method of claim 2, wherein the iron salt is Fe (ClO)4)39H2O、Fe(SO4)3Or FeCl3。
7. The method of claim 2, wherein the method is carried out in an organic solvent, and the organic solvent is N, N-dimethylformamide.
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