CN109534961B - Method for synthesizing 4-alkylresorcinol by solvent-free system - Google Patents
Method for synthesizing 4-alkylresorcinol by solvent-free system Download PDFInfo
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- CN109534961B CN109534961B CN201811622892.3A CN201811622892A CN109534961B CN 109534961 B CN109534961 B CN 109534961B CN 201811622892 A CN201811622892 A CN 201811622892A CN 109534961 B CN109534961 B CN 109534961B
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- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/001—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain
- C07C37/002—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain by transformation of a functional group, e.g. oxo, carboxyl
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- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/455—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation with carboxylic acids or their derivatives
Abstract
The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing 4-alkylresorcinol by a solvent-free system, which comprises the following steps: (1) uniformly mixing resorcinol, zinc chloride and alkyl acid, heating, stirring, reacting, cooling, adding water to precipitate solid, filtering, drying, and recrystallizing to obtain 4-acyl resorcinol; (2) dissolving 4-acylresorcinol in trifluoroacetic acid, dropwise adding triethylsilane, heating, stirring, reacting, cooling, standing, layering, extracting and drying an organic layer, filtering and concentrating to obtain a crude product, and recrystallizing to obtain the 4-alkylresorcinol. According to the invention, the triethylsilane/trifluoroacetic acid system is applied to the synthesis of 4-alkylresorcinol for the first time, the reaction conditions are milder and easy to control, and the post-treatment method is simple; and because no solvent is contained in the system, the waste generated in industrial amplification is greatly reduced, so that the whole process is more environment-friendly.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing 4-alkylresorcinol by a solvent-free system.
Background
The alkyl resorcinol is a chemical intermediate with wide application, is industrially used as an anticorrosive agent and a bactericide, and is applied to components of epoxy resin and some polymers and the like; is used as a medicine and food preservative in life, and is used for hair styling, skin bleaching and the like in the field of beauty and skin care. In recent years, 4-alkylresorcinol is found to have a good inhibition effect on tyrosinase, so that the melanin generation and deposition of the skin are effectively controlled, and the obvious skin brightening and whitening effects are generated, and the market demand is particularly increased in Asia areas.
Currently, the synthesis of 4-alkylresorcinols in industry is mainly obtained by two reactions: the first step is that resorcinol is taken as raw material, and Friedel-crafts acylation reaction is carried out on resorcinol and corresponding alkyl acyl chloride or acid anhydride under the action of Lewis acid such as aluminum trichloride and the like (Gazzetta Chimica Italiana,1984,114,359-361) to prepare corresponding 4-acyl resorcinol; or reacting resorcinol with the corresponding alkyl acid under hydrofluoric acid (pctint. appl.,2008104297) or zinc chloride (organic chemistry, 1990,10,70-73) conditions to give 4-acyl resorcinol; in the second step, 4-acylresorcinol is reduced to the corresponding 4-alkylresorcinol, typically by zinc amalgam reduction (J.Am.chem.Soc.,1921,43, 348-360). 4-alkylresorcinols are also obtained by pressure-catalyzed hydrogenation of palladium on carbon or aluminum nickel (Indian Pat. Appl.,2012MU 01297).
The above preparation process has the following disadvantages in industrial production: in the first step, Friedel-crafts acylation under the action of aluminum trichloride generates a large amount of viscous solids during post-treatment, thereby causing great difficulty in purification; the second step, the zinc amalgam reduction method consumes a large amount of zinc powder, generates more solid wastes, needs a large amount of water washing, and is distilled and crystallized for multiple times; the operation is complicated. The palladium-carbon or aluminum-nickel metal catalyst is expensive, and a high recovery rate is economically required. In addition, the processes basically require an organic solvent system for reaction, and the generated organic waste liquid has great influence on the environment.
Chinese patent literature discloses a preparation method of 4-alkylresorcinol, the publication number of which is CN107805186A, the acylation process of the invention controls the dosage of catalyst and alkyl acid, the yield is obviously improved, the by-products are reduced, and the production cost is reduced; the reduction process adopts hydrogen for reduction, and avoids using a zinc amalgam reducing agent with high toxicity and high pollution. However, the invention adopts organic solvent systems such as toluene, xylene and cyclohexane, generates a large amount of organic waste liquid, and is not beneficial to environmental protection.
Disclosure of Invention
In order to overcome the problems that the traditional synthesis process of 4-alkylresorcinol depends on an organic solvent system and is not beneficial to environmental protection, the invention provides a method for synthesizing 4-alkylresorcinol in a solvent-free system, the method firstly applies a triethylsilane/trifluoroacetic acid system to the synthesis of 4-alkylresorcinol, the reaction condition is milder, and the post-treatment method is simple; and because no solvent is contained in the system, the waste generated in industrial amplification is greatly reduced, so that the whole process is more environment-friendly.
In order to achieve the purpose, the invention adopts the following technical scheme:
a method for synthesizing 4-alkyl resorcinol by a solvent-free system comprises the following steps:
(1) mixing resorcinol, zinc chloride and alkyl acid, heating to a certain temperature, stirring, cooling the reaction solution after the reaction is completed, pouring into water, stirring, filtering out a large amount of precipitated solid, washing with water, drying, and recrystallizing to obtain 4-acyl resorcinol;
(2) dissolving 4-acylresorcinol in trifluoroacetic acid, dropwise adding triethylsilane, heating to a certain temperature, stirring, cooling the reaction solution after the reaction is completed, and then pouring into water and stirring; stopping stirring, standing and layering the reaction solution, extracting and drying an organic layer, filtering and concentrating to obtain a crude product, and recrystallizing to obtain the 4-alkylresorcinol.
The synthesis method of the invention is carried out according to the following equation:
the invention firstly uses resorcinol and alkyl acid to react to prepare 4-acyl resorcinol, and then uses triethyl silicane to reduce under the action of trifluoroacetic acid to prepare 4-alkyl resorcinol. The two-step reaction of the method does not adopt any organic solvent, so that the environmental protection cost is effectively reduced, and the reaction condition is milder than that of the existing method; the step 2 reaction avoids using a zinc amalgam reducing agent with high toxicity and high pollution and a metal catalyst with high cost and difficult recovery. The improvement of the whole method has important significance for industrialization.
Preferably, in the step (1), the reaction temperature is controlled to be 80-120 ℃. The reaction is more complete and byproducts are less in the temperature range, when the reaction temperature is lower than 80 ℃, more raw materials are incompletely reacted in the system, and the conversion rate is lower; when the reaction temperature is higher than 120 ℃, more byproducts are generated in the system, so that the reaction temperature must be strictly controlled to obtain higher selectivity and product yield.
Preferably, in the step (1), the molar ratio of the resorcinol to the alkyl acid is controlled to be 1: (1-2); preference is given to using 1: 1.5 molar ratio. The selectivity and yield of the reaction in the molar ratio are better, and when the molar ratio of the resorcinol to the alkyl acid is less than 1:2, a polyacylation substituted byproduct is easily generated in a system.
Preferably, in the step (1), the molar ratio of the resorcinol to the zinc chloride is controlled to be 1: (1-2); preference is given to using 1: 1.3. the reaction yield in the molar ratio is better, and the generated by-products are less.
Since 2-position acylation, 4, 6-position or 2, 4-position diacylation, or even 2,4, 6-position triacylation by-products are easily generated in the acylation process of the step (1), the molar ratio of resorcinol to alkyl acid and the reaction temperature must be strictly controlled, and the selectivity and yield of the reaction are improved under the above process conditions.
Preferably, in the step (2), the reaction temperature is controlled to be 40-80 ℃, and preferably 60 ℃. The reaction is more complete and byproducts are less in the temperature range, when the reaction temperature is lower than 40 ℃, more raw materials are incompletely reacted in the system, and the conversion rate is lower; when the reaction temperature is higher than 80 ℃, more byproducts are generated in the system, so that the reaction temperature must be strictly controlled to obtain higher selectivity and product yield.
Preferably, in the step (2), the molar ratio of the 4-acylresorcinol to the trifluoroacetic acid is controlled to be 1: (2-10); preference is given to using 1: 5. the reaction yield is high in the molar ratio, the post-treatment is easy, when the molar ratio of the 4-acylresorcinol to the trifluoroacetic acid is less than 1:10, the post-treatment is difficult due to the large amount of the trifluoroacetic acid in the system, and the reaction is difficult when the molar ratio is more than 1: 2.
Preferably, in the step (2), the molar ratio of the 4-acylresorcinol to the triethylsilane is controlled to be 1: (2-5), preferably 1: 3. the reaction yield in the molar ratio is higher, the number of byproducts is less, when the molar ratio of the 4-acylresorcinol to the triethylsilane is less than 1:5, a system can generate more silicon-containing byproducts which are not easy to separate and purify, and the reaction is difficult to carry out when the molar ratio is more than 1: 2.
A 4-alkylresorcinol synthesized by the method of any one of the above, wherein the alkyl group of the 4-alkylresorcinol is selected from one of a linear C2-C10 alkyl group and a branched C3-C10 alkyl group.
Therefore, the invention has the following beneficial effects: according to the invention, the triethylsilane/trifluoroacetic acid system is applied to the synthesis of 4-alkylresorcinol for the first time, the reaction conditions are milder and easy to control, and the post-treatment method is simple; and because no solvent is contained in the system, the waste generated in industrial amplification is greatly reduced, so that the whole process is more environment-friendly.
Drawings
FIG. 1 is a High Performance Liquid Chromatogram (HPLC) of 4-n-butyrylresorcinol obtained in example 1.
FIG. 2 is a chromatographic mass spectrum (GC) of 4-n-butylresorcinol obtained in example 1.
Detailed Description
The technical solution of the present invention is further specifically described below by using specific embodiments and with reference to the accompanying drawings.
In the present invention, all the equipment and materials are commercially available or commonly used in the art, and the methods in the following examples are conventional in the art unless otherwise specified.
The synthesis method of the embodiment of the invention is carried out according to the following equation:
example 1
(1) The starting resorcinol (500g,4.54mol) and zinc chloride (804g,5.9mol) were dissolved in n-butyric acid (600g,6.81mol), heated to 100 ℃ and stirred. Cooling the reaction solution and adding the reaction solution into water after the raw materials completely react, separating out a large amount of solid after stirring, filtering and washing the solid, drying the obtained solid, and recrystallizing the dried solid to obtain 4-n-butyrylresorcinol (724g, figure 1, HPLC: 98.3%);
(2) 4-n-butyrylresorcinol (724g,4.02mol) was dissolved in trifluoroacetic acid (2.29kg,20.1mol), cooled to 0 ℃ in an ice-water bath, triethylsilane (1.4kg,12.06mol) was added dropwise, and after the addition, the reaction was heated to 60 ℃ and stirred overnight. After the raw materials completely react, the reaction solution is poured into water for quenching, the mixture is continuously stirred and then stands for layering, an organic layer is extracted by ethyl acetate, a combined organic phase is washed by saturated common salt water, dried by anhydrous sodium sulfate, filtered and concentrated to obtain 736g of a crude product. The crude product was recrystallized from n-hexane and dichloromethane to give 4-n-butylresorcinol (601g, FIG. 2, GC: 99.9%) in an overall yield of 79.6%.
Example 2
(1) The starting resorcinol (500g,4.54mol) and zinc chloride (618g,4.54mol) were dissolved in n-butyric acid (400g,4.54mol), heated to 80 ℃ and stirred. Cooling the reaction liquid and adding the reaction liquid into water when the raw materials react completely, separating out a large amount of solid after stirring, filtering and washing the solid, drying the obtained solid, and recrystallizing the dried solid to obtain 4-n-butyrylresorcinol (561 g);
(2) 4-n-butyrylresorcinol (561g,3.1mol) was dissolved in trifluoroacetic acid (707g,6.2mol), cooled to 0 ℃ in an ice-water bath, triethylsilane (721g,6.2mol) was added dropwise, and after the addition, the reaction solution was heated to 40 ℃ and stirred overnight. After the reaction of the raw materials was completed, the reaction solution was poured into water to quench, and after further stirring, the mixture was allowed to stand for layering, the organic layer was extracted with ethyl acetate, the combined organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and then filtered and concentrated to obtain 524g of a crude product. The crude product was recrystallized from n-hexane and dichloromethane to give 4-n-butylresorcinol (286g) in 37.9% overall yield.
Example 3
(1) Raw materials resorcinol (500g,4.54mol) and zinc chloride (1.24kg,9.08mol) were dissolved in n-butyric acid (800g,9.08mol), heated to 120 ℃ and stirred. Cooling the reaction liquid and adding the reaction liquid into water after the raw materials completely react, separating out a large amount of solid after stirring, filtering and washing the solid, drying the obtained solid, and recrystallizing the dried solid to obtain 4-n-butyrylresorcinol (602 g);
(2) 4-n-butyrylresorcinol (602g,3.34mol) was dissolved in trifluoroacetic acid (3.81kg,33.4mol), cooled to 0 ℃ in an ice-water bath, triethylsilane (1.94kg,16.7mol) was added dropwise, and after the addition, the reaction was heated to 80 ℃ and stirred overnight. After the reaction of the raw materials was completed, the reaction solution was poured into water to quench, and after further stirring, the mixture was allowed to stand for separation, the organic layer was extracted with ethyl acetate, the combined organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and then filtered and concentrated to obtain 617g of a crude product. The crude product was recrystallized from n-hexane and dichloromethane to give 4-n-butylresorcinol (425g) in 56.3% overall yield.
The characterization mode and the result of the product in each step of the embodiment 2 and the embodiment 3 of the invention are similar to those of the embodiment 1, and are not repeated herein.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention in any way, and other variations and modifications may be made without departing from the spirit of the invention as set forth in the claims.
Claims (1)
1. A method for synthesizing 4-alkyl resorcinol by a solvent-free system is characterized by comprising the following steps:
(1) uniformly mixing resorcinol, zinc chloride and alkyl acid, heating and stirring for reaction, cooling reaction liquid and adding into water when the raw materials are completely reacted, separating out a large amount of solids after stirring, filtering and washing with water, drying the obtained solids, and recrystallizing to obtain 4-acyl resorcinol; controlling the reaction temperature to be 80-120 ℃; the molar ratio of the resorcinol to the alkyl acid is controlled to be 1: (1-2); the molar ratio of the resorcinol to the zinc chloride is controlled to be 1: (1-2); the alkyl acid is n-butyric acid;
(2) dissolving the 4-n-butyrylresorcinol obtained in the step (1) in trifluoroacetic acid, dropwise adding triethylsilane, heating, stirring, reacting, cooling, standing, layering, extracting and drying an organic layer, filtering and concentrating to obtain a crude product, and recrystallizing to obtain 4-alkylresorcinol; controlling the reaction temperature to be 40-80 ℃; the molar ratio of the 4-n-butyrylresorcinol to the trifluoroacetic acid is controlled to be 1: (2-10); the molar ratio of the 4-n-butyrylresorcinol to the triethylsilane is controlled to be 1: (2-5); the 4-alkyl resorcinol is 4-n-butyl resorcinol.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| DE3108265A1 (en) * | 1981-03-05 | 1982-09-16 | Riedel-De Haen Ag, 3016 Seelze | "METHOD FOR PRODUCING A 2-ALKYLPHENOL" |
| CN103159608A (en) * | 2011-12-14 | 2013-06-19 | 南京华狮化工有限公司 | A method for preparing resorcinol alkyl ketones |
| CN103159596A (en) * | 2011-12-14 | 2013-06-19 | 南京华狮化工有限公司 | Preparation method for 4-butylresorcinol |
| CN107805186A (en) * | 2017-10-27 | 2018-03-16 | 南京斯拜科生化实业有限公司 | A kind of preparation method of 4 alkyl-resorcin |
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