阅读说明：本技术 一种取代苯酚的合成方法 (Synthesis method of substituted phenol ) 是由 刘显伟 马青松 马心旺 孙东艳 魏力璟 赖彭莹 朱华志 于 2020-05-19 设计创作，主要内容包括：本发明提出了一种取代苯酚的合成方法,通过以取代苯作为起始原料制得目标产物取代苯酚,整个合成过程选择性高、产率高、操作方便且原子经济性高。(The invention provides a method for synthesizing substituted phenol, which prepares a target product substituted phenol by using substituted benzene as a starting material, and has the advantages of high selectivity, high yield, convenient operation and high atom economy in the whole synthesis process.)

1. A method for synthesizing substituted phenol is characterized by comprising the following steps:

(1) carrying out Friedel-crafts alkylation reaction on substituted benzene shown in a formula I to obtain cyclopentyl benzene containing a substituent group or cyclohexyl benzene containing a substituent group shown in a formula II;

(2) performing oxidation reaction on the substituted cyclopentyl benzene or the substituted cyclohexyl benzene shown in the formula II to obtain substituted phenyl cyclopentyl hydroperoxide or substituted phenyl cyclohexyl hydroperoxide shown in the formula III;

(3) carrying out cracking reaction on phenyl cyclopentyl hydroperoxide containing substituent groups or phenyl cyclohexyl hydroperoxide containing substituent groups shown in a formula III to obtain substituted phenol;

in the formulas I, II and III, R is one or more substituent groups at any possible position on a benzene ring.

2. The method for synthesizing substituted phenol according to claim 1, wherein in the step (1), substituted benzene represented by formula I and alkylating agent are subjected to Friedel-crafts alkylation reaction under the condition of first catalyst to obtain substituted cyclopentyl benzene or substituted cyclohexyl benzene represented by formula II.

3. The method of claim 1, wherein the alkylating agent is cyclopentene, cyclohexene, or a halogenated cyclopentane, a halogenated cyclohexane, or a cyclopentanol, or a cyclohexanol; preferably, the halogenated cyclopentane is chloro-cyclopentane or bromo-cyclopentane, and the halogenated cyclohexane is chloro-cyclohexane or bromo-cyclohexane.

4. The method for synthesizing substituted phenol according to claim 2 or 3, wherein the first catalyst is a composite ionic liquid or molecular sieve catalyst prepared from Lewis acid, protonic acid, Lewis acid and triethylamine hydrochloride ionic liquid; preferably, the first catalyst is aluminum trichloride AlCl₃FeCl, ferric chloride₃Titanium tetrachloride TiCl₄ZnCl, zinc chloride₂SnCl, tin chloride₂Boron trifluoride BF₃Sulfuric acid H₂SO₄Phosphoric acid H₃PO₄HF, triethylamine hydrochloride-aluminium trichloride Et₃NHCl-AlCl₃The composite ionic liquid and the MCM-22 molecular sieve.

5. The method for synthesizing substituted phenol according to any one of claims 1 to 4, wherein the substituted benzene represented by formula I is mono-substituted benzene or poly-substituted benzene, R is alkyl, alkoxy, alkoxyalkyl, alkylamino, dialkylamino, acylamino, acyloxy, halogen, phenyl, substituted phenyl, fused ring aryl, substituted fused ring aryl, heterocyclic aryl or substituted heterocyclic aryl; preferably, the substituent of the substituted phenyl, the substituted condensed ring aromatic group and the substituted heterocyclic aromatic group is nitro, trihalomethyl, acyl, formyl, cyano, sulfonic acid group or carboxyl.

6. The method for synthesizing a substituted phenol according to any one of claims 1 to 5, wherein in the step (2), the substituted cyclopentylbenzene represented by the formula II or the substituted cyclohexylbenzene is subjected to an oxidation reaction with an oxidizing agent under the condition of a second catalyst to obtain a substituted phenylcyclopentyl hydroperoxide or a substituted phenylcyclohexyl hydroperoxide represented by the formula III.

7. The method of synthesizing a substituted phenol according to claim 6 wherein said oxidizing agent is air or oxygen;

the second catalyst is one or the combination of more of 2, 2, 6, 6-tetramethyl piperidine nitroxide free radical and derivatives thereof, N-hydroxyl substituted cyclic imide compounds and sodium carbonate;

wherein, the 2, 2, 6, 6-tetramethyl piperidine nitroxide free radical and the derivatives thereof are selected from one or more compounds with the following structures:

the N-hydroxy substituted cyclic imide compound is selected from one or more of N-hydroxyphthalimide, 4-amino-N-hydroxyphthalimide, 3-amino-N-hydroxyphthalimide, N-hydroxyphenetetrachlorophthalimide, N-hydroxytetrabromophthalimide, N-hydroxytoluenetriomide, N-hydroxyphenyl-1, 2, 4-trimethylimide, pyridine-2, 3-dicarboximide, N-hydroxysuccinimide or N-hydroxy (tartrimide).

8. The method for synthesizing a substituted phenol according to any one of claims 1 to 7, wherein in the step (3), the substituted phenylcyclopentyl hydroperoxide or the substituted phenylcyclohexyl hydroperoxide having a substituent represented by the formula III is subjected to a cleavage reaction in the presence of an acid catalyst to obtain a substituted phenol.

9. The method of claim 8, wherein the acid catalyst is one or more of perchloric acid, sulfuric acid, phosphoric acid, or p-toluenesulfonic acid.

Technical Field

The invention relates to the technical field of organic synthesis, in particular to a synthesis method of substituted phenol.

Background

The phenol derivative containing the substituent group is an important chemical intermediate and has important application in the fields of medicine, agriculture and high polymer. For example, ortho-cresol, meta-cresol and para-cresol, which have the simplest structures, can be used for synthesis of synthetic resins, intermediates of pesticides, herbicides, and the like, respectively; 4-nonyl phenol is used for synthesizing detergents, moisturizers, lubricating oil additives, plasticizers and the like; 5', 5-diallyl-2, 2' -biphenol (magnolol) is used in medicine as antifungal agent; 4, 5-diacetylene-2-methoxyphenol is one of the key raw materials for preparing the asymmetric dendritic resin with optical performance.

At present, there are two main methods for industrially producing corresponding phenol by using aromatic hydrocarbon as a raw material: the method has the disadvantages of multiple reaction steps, long route, complex operation process, serious corrosion to reaction equipment, higher cost, large amount of three wastes and serious environmental pollution, and belongs to a rejected process; although the method has high reaction atom economy, less three wastes and low cost, the byproduct acetone has no good economic benefit, the acetone production capacity is surplus at present in China and even in the whole world, the acetone is a raw material for preparing the virus, and the byproduct acetone is difficult to produce and has a value.

Conventional methods for synthesizing polysubstituted phenols also include oxidation of benzyl alcohol, hydrolysis of halogenated aromatics, Fries rearrangement of esters, demethylation of anisole compounds, etc., but these methods often suffer from one or more disadvantages such as low yield, poor selectivity, etc.

Disclosure of Invention

Based on the technical problems in the background art, the invention provides a method for synthesizing substituted phenol, which prepares the target product substituted phenol by using substituted benzene as a starting material, and has the advantages of high selectivity, high yield, convenient operation and high atom economy in the whole synthesis process.

The invention provides a method for synthesizing substituted phenol, which comprises the following steps:

(1) carrying out Friedel-crafts alkylation reaction on substituted benzene shown in a formula I to obtain cyclopentyl benzene containing a substituent group or cyclohexyl benzene containing a substituent group shown in a formula II;

(2) performing oxidation reaction on the substituted cyclopentyl benzene or the substituted cyclohexyl benzene shown in the formula II to obtain substituted phenyl cyclopentyl hydroperoxide or substituted phenyl cyclohexyl hydroperoxide shown in the formula III;

(3) carrying out cracking reaction on phenyl cyclopentyl hydroperoxide containing substituent groups or phenyl cyclohexyl hydroperoxide containing substituent groups shown in a formula III to obtain substituted phenol;

in the formulas I, II and III, R is one or more substituent groups at any possible position on a benzene ring.

Preferably, the substituted benzene shown in the formula I and an alkylating agent are subjected to Friedel-crafts alkylation reaction under the condition of a first catalyst to obtain the substituted cyclopentyl benzene or substituted cyclohexyl benzene shown in the formula II.

Preferably, the alkylating agent is cyclopentene, cyclohexene or halogenated cyclopentane, halogenated cyclohexane or cyclopentanol, cyclohexanol; preferably, the halogenated cyclopentane is chloro-cyclopentane or bromo-cyclopentane, and the halogenated cyclohexane is chloro-cyclohexane or bromo-cyclohexane.

In the step, substituted cyclopentyl benzene or substituted cyclohexyl benzene can be prepared by Friedel-crafts alkylation reaction of mono-substituted benzene or poly-substituted benzene and cyclopentene or cyclohexene; or the substituted cyclopentyl benzene or the substituted cyclohexyl benzene is prepared by the Friedel-crafts alkylation reaction of the mono-substituted benzene or the poly-substituted benzene and the halogenated cyclopentane or the halogenated cyclohexane; it is even possible to prepare substituted cyclopentylbenzenes or substituted cyclohexylbenzenes by Friedel-crafts alkylation of mono-or poly-substituted benzenes with cyclopentanol or cyclohexanol.

The mono-substituted benzene or poly-substituted benzene can be any of the following structures:

monosubstituted benzenes

Disubstituted benzenes

Trisubstituted benzenes

Tetra-substituted benzene

Penta-substituted benzene

R₁、R₂、R₃、R₄Or R₅Respectively selected from alkyl, alkoxy, alkoxyalkyl, alkylamino, dialkylamino, amido, acyloxy, halogen, phenyl, substituted phenyl, fused ring aryl, substituted fused ring aryl, heterocyclic aryl or substituted heterocyclic aryl;

the substituent in the substituted phenyl, the substituted condensed ring aromatic group and the substituted heterocyclic aromatic group can be nitro, trihalomethyl, acyl, formyl, cyano, sulfonic group or carboxyl;

R₁、R₂、R₃、R₄or R₅Each independently may be the same or different.

Preferably, the first catalyst is a compound ionic liquid or a molecular sieve catalyst prepared from Lewis acid, protonic acid, Lewis acid and triethylamine hydrochloride ionic liquid; preferably, the first catalyst is aluminum trichloride AlCl₃FeCl, ferric chloride₃Titanium tetrachloride TiCl₄ZnCl, zinc chloride₂SnCl, tin chloride₂Boron trifluoride BF₃Sulfuric acid H₂SO₄Phosphoric acid H₃PO₄HF, triethylamine hydrochloride-aluminium trichloride Et₃NHCl-AlCl₃The composite ionic liquid and the MCM-22 molecular sieve.

The temperature of the Friedel-crafts alkylation reaction is-10 to 60 ℃, and the reaction time is 1 to 24 hours.

Preferably, in the step (2), the substituted cyclopentyl-benzene or substituted cyclohexyl-benzene shown in the formula II is subjected to oxidation reaction with an oxidant under the condition of a second catalyst to obtain substituted phenyl-cyclopentyl-hydroperoxide or substituted phenyl-cyclohexyl-hydroperoxide shown in the formula III.

Preferably, the oxidant is air or oxygen;

the second catalyst is one or the combination of more of 2, 2, 6, 6-tetramethyl piperidine nitroxide free radical and derivatives thereof, N-hydroxyl substituted cyclic imide compounds and sodium carbonate;

wherein, the 2, 2, 6, 6-tetramethyl piperidine nitroxide free radical and the derivatives thereof are selected from one or more compounds with the following structures:

the N-hydroxy substituted cyclic imide compound is selected from one or more of N-hydroxyphthalimide, 4-amino-N-hydroxyphthalimide, 3-amino-N-hydroxyphthalimide, N-hydroxyphenetetrachlorophthalimide, N-hydroxytetrabromophthalimide, N-hydroxytoluenetriomide, N-hydroxyphenyl-1, 2, 4-trimethylimide, pyridine-2, 3-dicarboximide, N-hydroxysuccinimide or N-hydroxy (tartrimide).

In the step, the substituted cyclopentyl benzene or the substituted cyclohexyl benzene is oxidized by air or oxygen to obtain the substituted phenyl cyclopentyl hydroperoxide or the substituted phenyl cyclohexyl hydroperoxide, and the oxidant in the reaction is only oxygen or oxygen in the air, so that the cost is effectively reduced.

Preferably, the temperature of the oxidation reaction is 0-120 ℃.

Preferably, in the step (3), the substituted phenyl cyclopentyl hydroperoxide or substituted phenyl cyclohexyl hydroperoxide shown in the formula III is subjected to a cracking reaction under the condition of an acid catalyst to obtain the substituted phenol.

Preferably, the acid catalyst is one or a combination of more of perchloric acid, sulfuric acid, phosphoric acid or p-toluenesulfonic acid.

In the step, phenyl cyclopentyl hydroperoxide containing substituent groups or phenyl cyclohexyl hydroperoxide containing substituent groups is decomposed under the condition of acid catalyst to obtain the target product substituted phenol, and the reaction by-product cyclopentanone or cyclohexanone in the step is a very widely applied and very important chemical raw material, so the synthetic route has very high economic benefit.

Preferably, the temperature of the cleavage reaction is 0-60 ℃.

The synthesis method of the substituted phenol can be represented by the following reaction scheme:

the invention completely new uses substituted benzene as raw material to synthesize substituted phenol by three steps, the raw material is simple and easy to obtain, the reaction process is safe and environment-friendly, the three wastes are less, the reaction atom economy is high, the byproduct economic value is high, and the invention is very suitable for industrialized production.

Drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of 4-phenylphenol;

FIG. 2 is a nuclear magnetic hydrogen spectrum of 2-methyl-5-fluorophenol;

FIG. 3 is a nuclear magnetic hydrogen spectrum of 2, 4, 6-trimethylphenol;

FIG. 4 is a nuclear magnetic hydrogen spectrum of 4-dimethylaminophenol;

Detailed Description

For the purpose of facilitating an understanding of the present invention, the present invention will now be described by way of examples. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.