CN109534961A - A kind of method of solvent-free system synthesis 4- alkyl-resorcin - Google Patents
A kind of method of solvent-free system synthesis 4- alkyl-resorcin Download PDFInfo
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- CN109534961A CN109534961A CN201811622892.3A CN201811622892A CN109534961A CN 109534961 A CN109534961 A CN 109534961A CN 201811622892 A CN201811622892 A CN 201811622892A CN 109534961 A CN109534961 A CN 109534961A
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- alkyl
- resorcin
- resorcinol
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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 present invention relates to technical field of organic synthesis; a kind of more particularly to method of solvent-free system synthesis 4- alkyl-resorcin; the following steps are included: (1) is by resorcinol; zinc chloride is uniformly mixed with alkyl acid; heating stirring reaction; after cooling plus elutriation goes out solid, and filtering, dry, recrystallization obtain 4- acyl group resorcinol；(2) 4- acyl group resorcinol is dissolved in trifluoroacetic acid, triethylsilane is added dropwise, heating stirring reaction, cooling, stratification, organic layer extraction, which dries, filters, is concentrated to give crude product, recrystallizes to get 4- alkyl-resorcin.Triethylsilane/trifluoroacetic acid system is applied to the synthesis of 4- alkyl-resorcin by the present invention for the first time, and reaction condition is more mild easily controllable, and post-processing approach is simple；And due to not having solvent in system, the waste material generated in industry amplification also greatly reduces, and keeps entire technique more environmentally protective.
Description
Technical field
The present invention relates to technical field of organic synthesis more particularly to a kind of solvent-free system to synthesize 4- alkyl-resorcin
Method.
Background technique
Alkyl-resorcin is a kind of widely used chemical intermediate, is industrially used as anticorrosive, fungicide,
Applied to epoxy resin and the constituent of some polymer etc.；It is used as drug and food preservative, Yi Ji in life
Beauty and skin care field is for hair fixing and depigmentation of skin etc..In recent years, 4- alkyl-resorcin was found it to tyrosinase
There is good inhibitory effect, to effectively control the melanin production and deposition of skin, apparent blast whitening is generated to skin
The increase of effect, market demand is particularly evident in Asia.
Currently, the synthesis of 4- alkyl-resorcin in the industry is mainly made by two-step reaction: the first step is with isophthalic two
Phenol is raw material, carries out friedel-crafts acylation with corresponding alkyl acyl chloride or acid anhydrides under the effect of the Lewis acid such as alchlor
Corresponding 4- acyl group resorcinol is made in (Gazzetta Chimica Italiana, 1984,114,359-361)；Or in hydrogen fluorine
Under the conditions of sour (PCTInt.Appl., 2008104297) or zinc chloride (organic chemistry, 1990,10,70-73), by resorcinol
It reacts to obtain 4- acyl group resorcinol with corresponding alkyl acid；Second step then usually uses zinc amalgam reduction method
(J.Am.Chem.Soc., 1921,43,348-360) restores 4- acyl group resorcinol to obtain corresponding 4- alkyl-resorcin.
In addition the pressurized catalysis of also useful palladium carbon or aluminium nickel (Indian Pat.Appl., 2012MU01297), which hydrogenates, is made between 4- alkyl
Benzenediol.
Above-mentioned preparation process has the disadvantages that the friedel-crafts acylation of first step alchlor effect exists in the industrial production
A large amount of sticky solids are generated when post-processing, cause larger difficulty to purifying；Second step zinc amalgam reduction method consumption zinc powder amount is big, produces
Raw solid waste is more, needs massive laundering, repeatedly distillation crystallization；It is cumbersome.The metallic catalysts higher cost such as palladium carbon or aluminium nickel,
Economically consider to need the higher rate of recovery.And process above requires organic solvent system substantially to be reacted, and produces
Raw organic liquid waste has greater environmental impacts.
" a kind of preparation method of 4- alkyl-resorcin ", notification number CN are disclosed in Chinese patent literature
107805186A, the invention acylation process control the dosage of catalyst and alkyl acid, significantly improve yield, reduce by-product
And reduce production cost；Reduction process uses hydrogen reducing, avoids the zinc amalgam reducing agent using high poison high pollution.But
The invention uses toluene, dimethylbenzene, and the organic solvent systems such as hexamethylene generate a large amount of organic liquid wastes, are unfavorable for environmental protection.
Summary of the invention
The present invention is unfavorable for environmental protection to overcome 4- alkyl-resorcin traditional synthesis dependent on organic solvent system
The problem of, a kind of method of solvent-free system synthesis 4- alkyl-resorcin is provided, this method is for the first time by triethylsilane/tri-
Fluoroacetic acid system is applied to the synthesis of 4- alkyl-resorcin, and reaction condition is milder, and post-processing approach is simple；And due to
There is no solvent in system, the waste material generated in industry amplification also greatly reduces, and keeps entire technique more environmentally protective.
To achieve the goals above, the invention adopts the following technical scheme:
A kind of method of solvent-free system synthesis 4- alkyl-resorcin, comprising the following steps:
(1) by raw material resorcinol, zinc chloride is mixed with alkyl acid, is heated to certain temperature and is stirred, after fully reacting
Reaction solution is cooling, it is subsequently poured into water and stirs, a large amount of solids of precipitation are dry after drainage is washed, and are then recrystallized to give
4- acyl group resorcinol；
(2) 4- acyl group resorcinol is dissolved in trifluoroacetic acid, triethylsilane is added dropwise, is then heated to certain temperature and stirs
It mixes, it is after fully reacting that reaction solution is cooling, it is subsequently poured into water and stirs；Stop reaction solution stratification after stirring, organic layer
Crude product is obtained through filtering and concentrating after extraction is dry, then by being recrystallized to give 4- alkyl-resorcin.
Synthetic method of the invention is carried out according to following equation:
The present invention, which is reacted first with resorcinol and alkyl acid, is made 4- acyl group resorcinol, then acts in trifluoroacetic acid
4- alkyl-resorcin is made in lower restored with triethylsilane.The two-step reaction of this method does not use any organic solvent, has
Effect reduces environmentally friendly cost, and reaction condition is milder than existing method；Step 2 reaction is avoided using high poison high pollution
Zinc amalgam reducing agent and metallic catalyst with high costs and that recycling is difficult.The improvement of entire method has industrialization
Significance.
Preferably, reaction temperature is controlled at 80~120 DEG C in step (1).In the temperature range reaction more completely and
By-product is less, when reaction temperature is lower than 80 DEG C, the reaction of more raw material is had in system not exclusively, conversion ratio is lower；Work as reaction
Temperature is higher than 120 DEG C, more by-product can be generated in system, therefore, it is necessary to which strict control reaction temperature, can just access higher
Selectivity and product yield.
Preferably, the molar ratio of the resorcinol and alkyl acid is controlled in 1:(1~2 in step (1))；Preferential choosing
With the molar ratio of 1:1.5.The selectivity and yield reacted in the molar ratio are more excellent, when the molar ratio of resorcinol and alkyl acid is small
The by-products for being acylated and replacing are easy to produce in 1:2, system more.
Preferably, in step (1), the resorcinol and control with the molar ratio of zinc chloride in 1:(1~2)；Preferentially
Select 1:1.3.Reaction yield is more excellent in the molar ratio, and the by-product generated is less.
Due to being easy to produce 2- acylations in the acylation process of step (1), 4,6- or 2,4- double acylations, very
Three to 2,4,6- are acylated by-product, so must strictly regulate and control the molar ratio of resorcinol and alkyl acid, and reaction
Temperature improves the selectivity and yield of reaction under above-mentioned process conditions.
Preferably, reaction temperature is controlled at 40~80 DEG C in step (2), the reaction temperature of preferential 60 DEG C of selection.The temperature
It spends in range reaction more completely and by-product is less, when reaction temperature is lower than 40 DEG C, the reaction of more raw material is had in system not
Completely, conversion ratio is lower；When reaction temperature be higher than 80 DEG C, more by-product can be generated in system, therefore, it is necessary to which strict control is anti-
Temperature is answered, higher selectivity and product yield can be just accessed.
Preferably, in step (2), the molar ratio control of the 4- acyl group resorcinol and trifluoroacetic acid 1:(2~
10)；It is preferential to select 1:5.Reaction yield is higher in the molar ratio and post-processing is relatively easy to, when 4- acyl group resorcinol and trifluoro
The molar ratio of acetic acid is less than 1:10, and largely existing trifluoroacetic acid makes post-processing more difficult to system, and molar ratio is greater than 1:
2, reaction is then difficult to carry out.
Preferably, in step (2), the molar ratio control of the 4- acyl group resorcinol and triethylsilane 1:(2~
5) 1:3, is preferentially selected.Reaction yield is higher in the molar ratio and by-product is less, when 4- acyl group resorcinol and triethyl group silicon
The molar ratio of alkane is less than 1:5, and the more siliceous by-product for being not readily separated purifying can be generated in system, and molar ratio is greater than 1:2, instead
Answer then more difficult progress.
A kind of 4- alkyl-resorcin synthesized by any of the above-described method, alkyl in the 4- alkyl-resorcin
It is a kind of in 2-C10 alkyl group of straight chain C and branch C3-C10 alkyl group.
Therefore, the invention has the following beneficial effects: the present invention to be for the first time applied to triethylsilane/trifluoroacetic acid system
The synthesis of 4- alkyl-resorcin, reaction condition is more mild easily controllable, and post-processing approach is simple；And due to not having in system
There is solvent, the waste material generated in industry amplification also greatly reduces, and keeps entire technique more environmentally protective.
Detailed description of the invention
Fig. 1 is the high-efficient liquid phase chromatogram (HPLC) of the positive bytyry resorcinol of 4- made from embodiment 1.
Fig. 2 is the chromatographic mass spectrometry figure (GC) of Lucin made from embodiment 1.
Specific embodiment
Below by specific embodiment, and in conjunction with attached drawing, the technical solutions of the present invention will be further described.
In the present invention, if not refering in particular to, all devices and raw material is commercially available or the industry is common are following
Method in embodiment is unless otherwise instructed conventional method in that art.
The synthetic method of the embodiment of the present invention is carried out according to following equation:
Embodiment 1
(1) by raw material resorcinol (500g, 4.54mol) and zinc chloride (804g, 5.9mol) be dissolved in n-butyric acie (600g,
In 6.81mol), it is heated to 100 DEG C and stirs.To raw material fully reacting, by reaction solution cooling and it is added to the water, it is big after stirring
Measure solid to be precipitated, filter and wash, be recrystallized to give after obtained solid is dry the positive bytyry resorcinol of 4- (724g, Fig. 1,
HPLC:98.3%)；
(2) the positive bytyry resorcinol (724g, 4.02mol) of 4- is dissolved in trifluoroacetic acid (2.29kg, 20.1mol),
Ice-water bath is cooled to 0 DEG C, is added dropwise triethylsilane (1.4kg, 12.06mol), and after adding, reaction solution is heated to 60 DEG C, stirred
Night.After raw material fully reacting, reaction solution is poured into water and is quenched, and continues stratification after stirring, organic layer ethyl acetate
Extraction, combined organic phase are washed with saturated common salt, and anhydrous sodium sulfate is dry, and then filtering and concentrating obtains crude product 736g.It should
Crude product n-hexane and recrystallize with dichloromethane obtain Lucin (601g, Fig. 2, GC:99.9%), total recovery
79.6%.
Embodiment 2
(1) by raw material resorcinol (500g, 4.54mol) and zinc chloride (618g, 4.54mol) be dissolved in n-butyric acie (400g,
In 4.54mol), it is heated to 80 DEG C and stirs.To raw material fully reacting, by reaction solution cooling and it is added to the water, it is big after stirring
It measures solid to be precipitated, filters and wash, be recrystallized to give the positive bytyry resorcinol (561g) of 4- after obtained solid is dry；
(2) the positive bytyry resorcinol (561g, 3.1mol) of 4- is dissolved in trifluoroacetic acid (707g, 6.2mol), ice water
Bath is cooled to 0 DEG C, is added dropwise triethylsilane (721g, 6.2mol), after adding, reaction solution is heated to 40 DEG C, is stirred overnight.Raw material
After fully reacting, reaction solution is poured into water and is quenched, and continue stratification after stirring, organic layer is extracted with ethyl acetate, and closes
And organic phase washed with saturated common salt, anhydrous sodium sulfate is dry, and then filtering and concentrating obtains crude product 524g.The crude product is used
N-hexane and recrystallize with dichloromethane obtain Lucin (286g), total recovery 37.9%.
Embodiment 3
(1) raw material resorcinol (500g, 4.54mol) and zinc chloride (1.24kg, 9.08mol) is dissolved in n-butyric acie
In (800g, 9.08mol), it is heated to 120 DEG C and stirs.To raw material fully reacting, by reaction solution cooling and it is added to the water, stirs
A large amount of solids are precipitated after mixing, and filter and wash, and are recrystallized to give the positive bytyry resorcinol of 4- after obtained solid is dry
(602g)；
(2) the positive bytyry resorcinol (602g, 3.34mol) of 4- is dissolved in trifluoroacetic acid (3.81kg, 33.4mol),
Ice-water bath is cooled to 0 DEG C, is added dropwise triethylsilane (1.94kg, 16.7mol), and after adding, reaction solution is heated to 80 DEG C, stirred
Night.After raw material fully reacting, reaction solution is poured into water and is quenched, and continues stratification after stirring, organic layer ethyl acetate
Extraction, combined organic phase are washed with saturated common salt, and anhydrous sodium sulfate is dry, and then filtering and concentrating obtains crude product 617g.It should
Crude product n-hexane and recrystallize with dichloromethane obtain Lucin (425g), total recovery 56.3%.
The characteristic manner and result and embodiment 1 of the product of the embodiment of the present invention 2 and each step of embodiment 3 are close, herein
It repeats no more.
The foregoing is merely presently preferred embodiments of the present invention, is not intended to limit the present invention in any form, and is not surpassing
There are also other variations and modifications under the premise of technical solution documented by claim out.
Claims (8)
1. a kind of method of solvent-free system synthesis 4- alkyl-resorcin, which comprises the following steps:
(1) by resorcinol, zinc chloride is uniformly mixed with alkyl acid, and heating stirring reaction, after cooling plus elutriation goes out solid, mistake
Filter, dry, recrystallization, obtain 4- acyl group resorcinol；
(2) the resulting 4- acyl group resorcinol of step (1) is dissolved in trifluoroacetic acid, triethylsilane is added dropwise, heating stirring is anti-
It answers, cooling, stratification, organic layer extraction, which dries, filters, is concentrated to give crude product, recrystallizes to get 4- alkyl-resorcin.
2. a kind of method of solvent-free system synthesis 4- alkyl-resorcin according to claim 1, which is characterized in that step
Suddenly in (1), reaction temperature is controlled at 80~120 DEG C.
3. a kind of method of solvent-free system synthesis 4- alkyl-resorcin according to claim 1, which is characterized in that step
Suddenly in (1), the molar ratio of the resorcinol and alkyl acid is controlled in 1:(1~2).
4. a kind of method of solvent-free system synthesis 4- alkyl-resorcin according to claim 1, which is characterized in that step
Suddenly in (1), the resorcinol and control with the molar ratio of zinc chloride in 1:(1~2).
5. a kind of method of solvent-free system synthesis 4- alkyl-resorcin according to claim 1, which is characterized in that step
Suddenly in (2), reaction temperature is controlled at 40~80 DEG C.
6. a kind of method of solvent-free system synthesis 4- alkyl-resorcin according to claim 1, which is characterized in that step
Suddenly in (2), the molar ratio of the 4- acyl group resorcinol and trifluoroacetic acid is controlled in 1:(2~10).
7. a kind of method of solvent-free system synthesis 4- alkyl-resorcin according to claim 1, which is characterized in that step
Suddenly in (2), the molar ratio of the 4- acyl group resorcinol and triethylsilane is controlled in 1:(2~5).
8. a kind of 4- alkyl-resorcin of method synthesis as claimed in claim 1, which is characterized in that the 4- alkane
Alkyl is a kind of in 2-C10 alkyl group of straight chain C and branch C3-C10 alkyl group in base resorcinol.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4419529A (en) * | 1981-03-05 | 1983-12-06 | Riedel-De Haen Aktiengesellschaft | Process for the preparation of a 2-alkylphenol |
| CN103159596A (en) * | 2011-12-14 | 2013-06-19 | 南京华狮化工有限公司 | Preparation method for 4-butylresorcinol |
| 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 |
| 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 |
-
2018
- 2018-12-28 CN CN201811622892.3A patent/CN109534961B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4419529A (en) * | 1981-03-05 | 1983-12-06 | Riedel-De Haen Aktiengesellschaft | Process for the preparation of a 2-alkylphenol |
| CN103159596A (en) * | 2011-12-14 | 2013-06-19 | 南京华狮化工有限公司 | Preparation method for 4-butylresorcinol |
| 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 |
| 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 |
Non-Patent Citations (3)
| Title |
|---|
| HERBERT MAYR等: "Selective in Ionic Reductions of Alcohols and Ketones with Triethyisilane / Trifluoroacetic Acid", 《TETRAHEDRON LETTERS》 * |
| JOHNSON, TREAT B.等: "Preparation of some alkyl derivatives of resorcinol and the relation of their structure to antiseptic properties", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
| SHIGEYUKI MIZOBUCHI等: "Antifungal Activity of 2,4-Dihydroxyacylophenones and Related Compounds", 《AGRZC. BIOI CHERN.》 * |
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