CN111393333A - Preparation method of 4-amino substituted cyclohexadienone derivative - Google Patents
Preparation method of 4-amino substituted cyclohexadienone derivative Download PDFInfo
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- CN111393333A CN111393333A CN202010342600.1A CN202010342600A CN111393333A CN 111393333 A CN111393333 A CN 111393333A CN 202010342600 A CN202010342600 A CN 202010342600A CN 111393333 A CN111393333 A CN 111393333A
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- C07—ORGANIC CHEMISTRY
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- C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C281/02—Compounds containing any of the groups, e.g. carbazates
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- C—CHEMISTRY; METALLURGY
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- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
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Abstract
The invention relates to a preparation method of a 4-amino substituted cyclohexadienone derivative, which comprises the following steps: adding catalyst Ag into the reactor in sequence2O, reactant I, reactant II and water, and placing the reactor in an ice bath for reaction for 0.5-10 hours. Extracting the reaction liquid with organic solvent, distilling the organic phase under reduced pressure to obtain crude product, and separating and purifying by column chromatography to obtain 4-amino substituted cyclohexadienone derivative. The reaction conditions of the invention are as follows: the method has the advantages of cheap and easily-obtained raw materials, short reaction time, simple and mild reaction conditions, good regioselectivity and important application value of products in organic synthesis, and is carried out in a green solvent water phase.
Description
Technical Field
The invention relates to a method for synthesizing 4-amino substituted cyclohexadienone derivatives by para-amination dearomatization of phenolic compounds catalyzed by transition metals.
Background
Cyclohexadienone is an important synthetic intermediate, can be used as an effective component for synthesis of complex molecules and natural products, and the structure can be obtained by dearomatization of phenol. Generally, dearomatization of phenols is achieved by high-valence iodine-mediated or transition metal-catalyzed alkylation and arylation, and few reports have been made on the amination dearomatization process of phenol to obtain 4-amino-substituted cyclohexadienone derivatives.
Phenol moieties are ubiquitous in natural products, dyes, drugs and materials, and are inexpensive and readily available raw materials for the construction of other compound molecules in chemical science. Therefore, it is very interesting to selectively functionalize phenolic compounds. However, the conversion of the phenolic C-H bond to other C-X bonds with high chemo-and regioselectivity is somewhat challenging: first, the free phenolic hydroxyl group is acidic and nucleophilic, typically resulting in O-H substitution in preference to C-H substitution; secondly, in electrophilic reaction, because the ortho-position and para-position on the aromatic ring are nucleophilic, the regioselectivity of the reaction is reduced; finally, phenol, as a classical electron-rich aromatic hydrocarbon, is susceptible to oxidative decomposition during the reaction.
Only a few documents report the use of chiral phosphoric acids or noble metals for the catalytic amination dearomatization of naphthols. Dearomatization amination reaction studies on phenolic compounds are less studied and are generally only applicable to phenolic compounds having C2 and C3 substituents. For phenolic compounds without C2 and C3 substituents, ortho amination occurs rather than aminating dearomatization.
Disclosure of Invention
The invention aims to provide a preparation method of a 4-amino substituted cyclohexadienone derivative, which has the advantages of simple process, mild reaction, environmental friendliness and high selectivity.
The purpose of the invention is realized by the following steps:
a preparation method of a 4-amino substituted cyclohexadienone derivative comprises the following steps:
(1) adding catalyst Ag into the reactor in sequence2O, a reactant I, a reactant II and solvent water, and placing the reactor in an ice bath to be stirred and react for 0.5-10 hours;
(2) extracting the obtained reaction liquid by using an organic solvent, distilling an organic phase under reduced pressure to obtain a crude product, and separating and purifying by using column chromatography to obtain a phenol compound aminated dearomatization product;
the first reactant is p-cresol;
the reactant II is any one of diisopropyl azodicarboxylate, di-tert-butyl azodicarboxylate and dibenzyl azodicarboxylate.
Preferably, the mole percentages of the catalyst, the first reactant and the second reactant are (1-5): 1: 2.
preferably, step (2) is to add water to the reaction solution and then extract the crude product with ethyl acetate for not less than 3 times.
Preferably, Ag2The purity of O is not less than 95%, and the water is ultrapure water, distilled water or tap water.
Preferably, the eluent in the chromatographic separation is a mixed solution of ethyl acetate and petroleum ether.
The invention also aims to provide a 4-amino substituted cyclohexadienone derivative prepared by the method.
The structural formula of the 4-amino substituted cyclohexadienone derivative is as follows:
the reaction formula of the invention is
The invention realizes the para-amination dearomatization preparation of the 4-amino-substituted cyclohexadienone derivative by phenol compounds through silver catalysis in a water phase and taking azocarboxylate as an amination reagent. The reaction is carried out in a green solvent water phase, the reaction time is short, the reaction condition is simple and mild, and the regioselectivity is good. It provides an effective method for synthesizing useful 4-amino substituted cyclohexadienone derivatives, and the product has important application value in organic synthesis. Meanwhile, if the dosage of the reactants is enlarged by 100 times, the yield of the reaction is still not affected, and the method is beneficial to industrial production.
Detailed Description
The following examples are provided to further illustrate the present invention for better understanding, but the present invention is not limited to the following examples.
Example 1
Preparation of 1- (1-methyl-4-oxocyclohexa-2, 5-dien-1-yl) hydrazine-1, 2-dicarboxylic acid diisopropyl ester:
adding 3 mol% of Ag as a catalyst in sequence2O, 0.2mmol of p-cresol, 0.4mmol of diisopropyl azodicarboxylate, 2m of L water and one of 5 magnetons, the reactor is placed in an ice bath for reaction for 0.5 hour, the reaction liquid is poured into a separating funnel, 15m of L water is added, extraction is carried out for 3 times by using 10m of L ethyl acetate, the obtained organic phases are combined and are dried by a rotary evaporator, and the crude product is separated and purified by column chromatography to obtain 44.7mg of diisopropyl 1- (1-methyl-4-oxocyclohexa-2, 5-diene-1-yl) hydrazine-1, 2-dicarboxylate as yellow oily liquid with the yield of 67%.
Determining the structure of the product by hydrogen spectrum and carbon spectrum of nuclear magnetic resonance1H NMR(400MHz,CDCl3):7.28(dd,J＝2.92Hz,J＝10.08Hz,1H),6.89–6.85(m,1H),6.71–6.63(m,1H),6.20–6.14(m,2H),5.00–4.81(m,2H),1.50(s,3H),1.31–1.25(m,6H),1.18–1.13(m,6H)；13C NMR(100MHz,CDCl3):185.4,157.0,154.9,152.4,152.1,127.3,71.1,70.5,60.5,25.5,22.1,22.0,21.9。
Example 2
Preparation of di-tert-butyl 1- (1-methyl-4-oxocyclohexa-2, 5-dien-1-yl) hydrazine-1, 2-dicarboxylate:
adding 3 mol% of Ag as a catalyst in sequence2O, 0.2mmol of p-cresol, 0.4mmol of di-tert-butyl azodicarboxylate, 2m L water and one of 5 # magnetons, the reactor is placed in an ice bath for reaction for 0.5 hour, the reaction liquid is poured into a separating funnel, 15m L water is added, 10m L ethyl acetate is used for extraction for 3 times, the obtained organic phases are combined and are dried by a rotary evaporator, and the crude product is separated and purified by column chromatography to obtain 27.0mg of the di-tert-butyl 1, 2-dicarboxylate 1- (1-methyl-4-oxocyclohexa-2, 5-diene-1-yl) hydrazine-1, 2-dicarboxylate as a white solid with the yield of 60%.
Determining the structure of the product by hydrogen spectrum and carbon spectrum of nuclear magnetic resonance1H NMR(400MHz,CDCl3):7.33(s,1H),6.94–6.79(m,2H),6.20–6.14(m,2H),1.50(s,12H),1.39(s,9H)；13C NMR(100MHz,CDCl3):185.4,156.3,152.8,126.8,82.5,81.6,60.2,28.1,28.0,25.6。
Example 3
Preparation of 1- (1-methyl-4-oxocyclohexa-2, 5-dien-1-yl) hydrazine-1, 2-dicarboxylic acid dibenzyl ester
Adding 3 mol% of Ag as a catalyst in sequence2O, 0.2mmol of p-cresol, 0.4mmol of dibenzyl azodicarboxylate, 2m of L water and one of 5 magnetons, the reactor is placed in an ice bath for reaction for 0.5 hour, the reaction liquid is poured into a separating funnel, 15m of L water is added, extraction is carried out for 3 times by using 10m of L ethyl acetate, the obtained organic phases are combined and are dried by a rotary evaporator, and the crude product is separated and purified by column chromatography to obtain 37.4mg of dibenzyl 1- (1-methyl-4-oxocyclohexa-2, 5-diene-1-yl) hydrazine-1, 2-dicarboxylic acid as a light yellow solid with the yield of 46%.
Determining the structure of the product by hydrogen spectrum and carbon spectrum of nuclear magnetic resonance1H NMR(400MHz,CDCl3):7.89(s,1H),7.39–7.33(m,10H),6.91(d,J＝10.48Hz,1H),6.20–6.11(m,2H),5.25–5.06(m,5H),1.53(s,3H)；13C NMR(100MHz,CDCl3):185.3,157.0,154.8,152.1,151.7,135.4,135.1,128.5,128.4,128.2,128.0,127.9,127.1,68.3,67.8,60.6,25.1。
While the foregoing is directed to the preferred embodiment of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow.
Claims (7)
1. A preparation method of a 4-amino substituted cyclohexadienone derivative is characterized by comprising the following steps:
(1) adding catalyst Ag into the reactor in sequence2O, a reactant I, a reactant II and solvent water, and placing the reactor in an ice bath to be stirred and react for 0.5-10 hours;
(2) extracting the obtained reaction liquid by using an organic solvent, distilling an organic phase under reduced pressure to obtain a crude product, and separating and purifying by using column chromatography to obtain a 4-amino substituted cyclohexadienone derivative;
the first reactant is p-cresol;
the reactant II is any one of diisopropyl azodicarboxylate, di-tert-butyl azodicarboxylate and dibenzyl azodicarboxylate.
2. The method of claim 1, wherein the equivalence ratio of reactant one to reactant two is 1: 2, the catalyst Ag2The mol percentage of O in the reaction system is 1-5 mol%.
3. The method according to claim 1, wherein the step (2) comprises adding water to the reaction solution and then extracting the crude product with ethyl acetate for not less than 3 times.
4. The method of claim 1, wherein Ag2The purity of O is not less than 95%, and the water is ultrapure water, distilled water or tap water.
5. The method according to claim 1, wherein the eluent in the chromatographic separation is a mixed solution of ethyl acetate and petroleum ether.
6. A4-amino substituted cyclohexadienone derivative, characterized by being prepared by the method of any one of claims 1 to 5.
7. The 4-amino substituted cyclohexadienone derivative according to claim 1, wherein the structural formula is:
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001066727A (en) * | 1999-08-27 | 2001-03-16 | Konica Corp | Heat-developable photosensitive material and processing method for the same |
| CN1636969A (en) * | 2003-12-15 | 2005-07-13 | 三星电子株式会社 | Phenylazomethylene-cyclohexadienone derivatives comprising electron withdrawing group and electrophotographic photoreceptor comprising the derivatives |
| CN101873801A (en) * | 2007-09-27 | 2010-10-27 | 巴斯夫欧洲公司 | Systemicity enhancers |
| CN108117507A (en) * | 2018-03-14 | 2018-06-05 | 吉首大学 | A kind of preparation method and use of azaspiro cyclohexadienone |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001066727A (en) * | 1999-08-27 | 2001-03-16 | Konica Corp | Heat-developable photosensitive material and processing method for the same |
| CN1636969A (en) * | 2003-12-15 | 2005-07-13 | 三星电子株式会社 | Phenylazomethylene-cyclohexadienone derivatives comprising electron withdrawing group and electrophotographic photoreceptor comprising the derivatives |
| CN101873801A (en) * | 2007-09-27 | 2010-10-27 | 巴斯夫欧洲公司 | Systemicity enhancers |
| CN108117507A (en) * | 2018-03-14 | 2018-06-05 | 吉首大学 | A kind of preparation method and use of azaspiro cyclohexadienone |
Non-Patent Citations (3)
| Title |
|---|
| LEE YOUNGHEE ET AL: "Temporary Inactivation of Plasma Amine Oxidase by Alkylhydrazines. A Combined Enzyme/Model Study Implicates Cofactor Reduction/Reoxidation but Cofactor Deoxygenation and Subsequent Reoxygenation in the Case of Hydrazine Itself", 《JOURNAL OF ORGANIC CHEMISTRY》 * |
| XIA ZILEI ET AL: "Chiral phosphoric acid catalyzed aminative dearomatization of α-naphthols/Michael addition sequence", 《NATURE COMMUNICATIONS》 * |
| 艾文英等: "邻甲亚基环己二烯酮在天然产物合成中的应用", 《有机化学》 * |
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