CN104387265B - A kind of preparation method of 4,5-dihydroxy-2-ar-Toluic acid - Google Patents

A kind of preparation method of 4,5-dihydroxy-2-ar-Toluic acid Download PDF

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CN104387265B
CN104387265B CN201410605252.7A CN201410605252A CN104387265B CN 104387265 B CN104387265 B CN 104387265B CN 201410605252 A CN201410605252 A CN 201410605252A CN 104387265 B CN104387265 B CN 104387265B
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benzyloxy
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CN104387265A (en
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孙雅泉
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Yancheng Teachers University
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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
    • C07C37/62—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by introduction of halogen; by substitution of halogen atoms by other halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/16—Preparation of ethers by reaction of esters of mineral or organic acids with hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/22—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogens; by substitution of halogen atoms by other halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/15—Preparation of carboxylic acids or their salts, halides or anhydrides by reaction of organic compounds with carbon dioxide, e.g. Kolbe-Schmitt synthesis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
    • C07C51/377—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups

Abstract

The invention discloses the preparation method of a kind of 4,5 dihydroxy 2 ar-Toluic acids, belong to fine chemistry industry and medicine intermediate field.The present invention is that raw material prepares intermediate III or V with 4 methylbenzene 1,2 diphenol, then is prepared intermediate compound IV by intermediate III or V, and intermediate compound IV is then converted to intermediate II, finally has intermediate II to prepare 4,5 dihydroxy 2 ar-Toluic acids.The present invention overcomes existing method raw material be difficult to obtain, by-product many, yield is the highest, cost is high, and step is numerous and diverse, dangerous, there is the problem of severe contamination.

Description

A kind of preparation method of 4,5-dihydroxy-2-ar-Toluic acid
Technical field
The present invention relates to one 4, the preparation method of 5-dihydroxy-2-ar-Toluic acid, belong in fine chemistry industry and medicine Mesosome field.
Background technology
4,5-dihydroxy-2-ar-Toluic acid is a kind of important medicine and fine-chemical intermediate.Its structural formula is as follows:
For 4, the preparation method of 5-dimethoxy-2-ar-Toluic acid, had following several: (1) utilizes 4,5-diformazan Epoxide-2-tolyl aldehyde is raw material, by oxidation generation 4,5-dimethoxy-2-ar-Toluic acid；Through deprotection, obtain mesh Mark product.The raw materials used source of the method is difficult to, thus limits its purposes.(2) it is former for utilizing 3,4-dimethoxybenzoic acid Material, with iodomethane reaction in the presence of isobutyl group lithium, generates the 4 of 35%, and 5-dimethoxy-2-ar-Toluic acid is accompanied simultaneously Along with substantial amounts of by-product, there is no productive value.(3) with 1,2-dimethoxy-4-methyl-benzene as raw material, in the presence of phosphorus oxychloride, The corresponding aldehyde of generation, more oxidized generation 4,5-dimethoxy-2-ar-Toluic acid is reacted with DMF.This method is because using trichlorine Oxygen phosphorus and pollute the heaviest.(4) with 1,2-dimethoxy-4-methyl-benzene as raw material, in the presence of lithium perchlorate, generation is reacted with acetic anhydride 3,4-dimethoxy-2-methyl acetophenone；3,4-dimethoxy-2-ar-Toluic acid is generated again with bromine reaction.(5) with 3,4-bis- Methoxy toluene is raw material, and respectively through reacting with NBS, tert-butyl lithium is reacted, generated 3 with carbon dioxide reaction again, 4-dimethoxy Base-2-ar-Toluic acid.Because tert-butyl lithium is easily caught fire, limit its purposes.(6) with 2-(2-bromo-3,4-dimethoxy phenyl- 1,3-dioxolanes is raw material, under butyl lithium effect, and iodomethane reaction, then react with silver nitrate, generate 3,4-diformazan Epoxide-2-ar-Toluic acid.But it is intended to generate 3 with this, 4-dihydroxy-2-ar-Toluic acid, needs to use substantial amounts of tribromide Boron, cost is high, pollutes weight, is not suitable for large-scale production.
Visible, existing synthetic method otherwise be raw material be difficult to obtain, by-product many, yield is the highest, cost is high, or is Step is numerous and diverse, dangerous, there is severe contamination.
Summary of the invention
The technical problem to be solved is to overcome the technological deficiency in said method, it is provided that a kind of product purity Height, yield height, low cost, preparation method simple to operate.
The technical solution adopted in the present invention is as it is shown in figure 1, with 4-methylbenzene-1,2-diphenol is raw material, prepares intermediate III or V, then prepared intermediate compound IV by preparation intermediate III or V, intermediate compound IV is converted into 4 via intermediate II, and 5-dihydroxy- 2-ar-Toluic acid.
Wherein, intermediate III is 4-bromine (or chlorine)-5-methyl isophthalic acid, 2-diphenol；Intermediate V is 4,5-bis-(replacement) benzyloxy Base toluene, or 4,5-bis-(replacement) pi-allyl epoxide toluene；Intermediate compound IV be 4,5-bis-(replacement) benzyloxy-2-bromine (or Chlorine) toluene, or 4,5-bis-(replacement) pi-allyl epoxide-2-bromine (or chlorine) toluene；Intermediate II is 4,5-bis-(replacement) benzyl Epoxide-2-methyl-benzoic acid, or 4,5-bis-(replacement) pi-allyl epoxide-2-methyl-benzoic acid.
Intermediate II, III, IV, V structural formula respectively as shown in formula (2), formula (3), formula (4), formula (5), R in formula1, R2Generation Table benzyl or the benzyl of various substituent group, pi-allyl or the pi-allyl of various substituent group.
The invention provides one and prepare 4, the method for 5-dihydroxy-2-ar-Toluic acid, is with alcohols as solvent, with 5%Pd/C, 10%Pd/C or PtO2Deng for catalyst, make intermediate II slough corresponding protection group by catalytic hydrogenation, obtain Target product, the response time is 1～6 hour, and answering temperature is 20 DEG C～90 DEG C, and reaction pressure is 1～4 atmospheric pressure.
In one embodiment of the invention, the mixing of one or more during described alcohol is methanol, ethanol, isopropanol Thing.
In another embodiment of the invention, described alcohol is isopropanol.
In another embodiment of the invention, the response time is 2 hours, and reaction temperature is 25 DEG C.
The preparation of described intermediate II, in one embodiment of the invention, is with ether as solvent, with intermediate compound IV is Raw material, forms Grignard reagent with magnesium metal or forms lithium salts with organolithium, then generating with carbon dioxide reaction；Intermediate compound IV and magnesium Or the mol ratio of organolithium reagent is 1:(1～2), reaction temperature is 30 DEG C～70 DEG C.
In a kind of embodiment of preparation intermediate II, the intermediate of intermediate compound IV total mole number 10%～15% will be accounted for IV and magnesium chips or organolithium and solvent mix, and are heated to micro-boiling, more slowly drip remaining intermediate compound IV solution, keep solution micro- Boiling state；After dropping, it is stirred for making reaction complete, in mixture, adds the carbon dioxide of excess, be sufficiently stirred for；To instead Answer the hydrochloric acid adding 2N in system to pH=1, under agitation reactant mixture is poured in frozen water, be filtrated to get solid intermediate II。
In a kind of embodiment of preparation intermediate II, described carbon dioxide is gas or dry ice.
In a kind of embodiment of preparation intermediate II, described ether is ether, propyl ether, oxolane, dioxane, second The mixture of one or more in glycol dimethyl ether.Preferably oxolane, dioxane or glycol dimethyl ether.
In a kind of embodiment of preparation intermediate II, described intermediate compound IV with the mol ratio of magnesium or organolithium reagent is 1:(1～2).
Preparation intermediate II a kind of embodiment in, described reaction temperature is 50 DEG C～60 DEG C, the response time be 3～ 7 hours.
In a kind of embodiment of preparation intermediate II, described organolithium preferably uses n-BuLi.
The preparation of described intermediate compound IV, in one embodiment of the invention, is with ether, dichloromethane, chloroform, tetrachloro Change carbon, 1, the mixture of one or more in 2-dichloroethanes, acetone, acetonitrile, DMF or DMSO is solvent, by intermediate III React in the presence of the alkali of intermediate III 2～5 times of molal quantitys with organohalogen compounds, intermediate III and organohalogen compounds mole Ratio is 1:2～4；Reaction temperature is 30 DEG C～100 DEG C.
In a kind of embodiment of preparation intermediate compound IV, alkali, intermediate III, solvent are mixed, stir half an hour Left and right, adds organohalogen compounds in mixture, is heated to 30～100 DEG C, and the response time is 3～7 hours, after reaction terminates, Filtration under diminished pressure, and remove solvent under reduced pressure and obtain solid；This solid is poured into water stirring again, filtration under diminished pressure, drains, obtain pale yellow colored solid Body intermediate compound IV.
In a kind of embodiment of preparation intermediate compound IV, described organohalogen compounds are benzyl chlorine, benzyl bromine, benzyl iodine, pi-allyl Chlorine, allyl bromide, bromoallylene or allyl iodide.Preferably benzyl chlorine.
In a kind of embodiment of preparation intermediate compound IV, described alkali is alkali-metal carbonate, bicarbonate or alkali gold Belong to hydroxide.Preferably potassium carbonate or sodium carbonate is optimal.
In a kind of embodiment of preparation intermediate compound IV, reaction mix and blend temperature is 70 DEG C.
In a kind of embodiment of preparation intermediate compound IV, described ether is ether, propyl ether, oxolane, dioxane, second Glycol dimethyl ether.
In a kind of embodiment of preparation intermediate compound IV, described solvent is acetone, acetonitrile or DMF.
The preparation of described preparation intermediate III, in one embodiment of the invention, be with various ethers, dichloromethane, Chloroform, carbon tetrachloride, 1, the mixture of one or more in 2-dichloroethanes is solvent, by 4-methylbenzene-1,2-diphenol with Halide reagent is 1:1～2 mixing in molar ratio, and in reaction bulb, temperature is reacted at-70 DEG C～-30 DEG C.
In a kind of embodiment of preparation intermediate III, by 4-methylbenzene-1,2-diphenol and stirring solvent are formed molten Liquid, inserts reaction system in the cooling bath of acetone and dry ice, is kept stirring for, and drips halide reagent, remove within half an hour Cooling bath, warms naturally to room temperature, solvent evaporated, recrystallization, filters, drains, and obtains intermediate III.
In a kind of embodiment of preparation intermediate III, described halide reagent is bromine, NaBr-Br2, NBS (N-bromo Succimide), NCS (N-chlorosuccinimide).
Preparation intermediate III a kind of embodiment in, described ether be ether, propyl ether, oxolane, dioxane or Glycol dimethyl ether.
In a kind of embodiment of preparation intermediate III, described solvent is dichloromethane, chloroform or 1,2-bis-chloroethene Alkane.
In a kind of embodiment of preparation intermediate III, described 4-methylbenzene-1,2-diphenol and halide reagent by mole Mix than for 1:1～2 ,-70 DEG C～-30 DEG C reactions.
The preparation of described intermediate compound IV, in one embodiment of the invention, is with ether, dichloromethane, chloroform, tetrachloro Changing carbon or 1, in 2-dichloroethanes, the mixture of one or more is solvent, with intermediate V as raw material, with bromine, NaBr-Br2、 The halide reagent reactions such as NBS, NCS；Intermediate V is 1:1～2 with the mol ratio of halide reagent, and reaction temperature is-70 DEG C～-30 ℃。
In a kind of embodiment of preparation intermediate compound IV, intermediate V is formed solution with solvent mix and blend, will reaction System is placed in the cooling bath of acetone and dry ice, is kept stirring for, and drips halide reagent, remove cold within half an hour in solution But groove, warms naturally to room temperature.Filtration under diminished pressure, drains, and obtains faint yellow solid intermediate compound IV.
In a kind of embodiment of preparation intermediate compound IV, described ether is ether, propyl ether, oxolane, dioxane, second Glycol dimethyl ether.
In a kind of embodiment of preparation intermediate compound IV, described solvent is dichloromethane, chloroform or 1,2-dichloroethanes.
In a kind of embodiment of preparation intermediate compound IV, described intermediate V is 1:1～2 with the mol ratio of halide reagent.
In a kind of embodiment of preparation intermediate compound IV, described reaction temperature is-70 DEG C～-30 DEG C.
The described preparation preparing intermediate V, in one embodiment of the invention, with ether or dichloromethane, chloroform, four Chlorination carbon, 1,2-dichloroethanes, the mixture of one or more in acetone, acetonitrile, DMF, DMSO is solvent；With 4-methyl Benzene-1,2-diphenol is raw material, with organohalogen compounds in 4-methylbenzene-1, reacts in the presence of the alkali of 2-diphenol 2～5 times of molal quantitys, 4-methylbenzene-1,2-diphenol is 1:2～4 with the mol ratio of halogenide, and reaction whipping temp is 30 DEG C～100 DEG C.
In a kind of embodiment preparing intermediate V, by alkali, 4-methylbenzene-1,2-diphenol, solvent, stirring mixing half About hour, adding organohalogen compounds, be heated to 30～100 DEG C in mixture, the response time is 3～7 hours, and reaction terminates After, filtration under diminished pressure also removes solvent under reduced pressure and obtains solid, the stirring that adds water, filtration under diminished pressure, drains in gained solid, obtains pale yellow colored solid Body intermediate V.
In another embodiment of the invention, with acetone, acetonitrile or DMF as solvent.
In another embodiment of the invention, described ether is ether, propyl ether, oxolane, dioxane, ethylene glycol Dimethyl ether etc..
In another embodiment of the invention, described organohalogen compounds are various benzyl chlorine, benzyl bromine, benzyl iodine, or various Allyl chloride, allyl bromide, bromoallylene, allyl iodide.
In another embodiment of the invention, organohalogen compounds are benzyl chlorine, and alkali is potassium carbonate or sodium carbonate.
In another embodiment of the invention, reaction temperature is 70 DEG C.
The important advantage of the present invention is: easy to operate and safe, and raw material is easy to get, product is prone to purification, and purity is high, yield is high.
Accompanying drawing explanation
Fig. 1 the technology of the present invention route and each intermediate structure formula, wherein, R1, R2 represent benzyl or substituted benzyl, allyl Base or substituted pi-allyl.
Detailed description of the invention
The purity of product uses high performance liquid chromatography normalization method to be measured.The computational methods that reaction yield uses It is: the theoretical yield of the actual production/reaction of product.
Embodiment 1 prepares intermediate III
To prepare 2-bromo-4, as a example by 5-orcin
To equipped with in 500 milliliters of three neck round bottom flasks of mechanical agitator, add 24.8g4-methylbenzene-1,2-diphenol (0.2mol) He 200 milliliters of dichloromethane, stirring forms solution.Reaction bulb is inserted in the cooling bath of acetone and dry ice, keep Stirring.Dripping 38.4g bromine (0.24mol) within half an hour, during dropping, in holding reaction bulb, temperature is-70 DEG C～-30 DEG C, drips After adding, remove cooling bath, warm naturally to room temperature.Solvent evaporated, recrystallization, filter, drain, obtain 38.2 grams of products, produce Rate is 94.2%, and purity is 93.8%.It is 98.1% solid that crude product obtains purity through ethyl acetate/petroleum ether (1:4) recrystallization 35.8 grams.
If with NaBr-Br equimolar with bromine2Replace bromine, use identical operational approach also can obtain 36.2 grams of purity to be The solid of 98.5%.
Embodiment 2 prepares intermediate V
To prepare 3, as a example by 4-benzyloxy toluene
To equipped with in 500 milliliters of three neck round bottom flasks of mechanical agitator, be initially charged 66.7g potassium carbonate (0.48mol), 24.8g4-methylbenzene-1,2-diphenol (0.2mol) and 250 milliliters of acetone, stir half an hour.60.8g benzyl is added in mixture Chlorine (0.48mol), is heated to reflux 5 hours, and reaction TLC follows the tracks of.After reaction terminates, filtering, add water stirring, filtration under diminished pressure, receipts Collection solid, drains, obtains faint yellow solid 56.9 grams, and productivity is 93.4%, purity 95.4%.
According to the benzyl bromo of identical mole for benzyl chlorine, using identical method, obtain 57.4 grams of solids, purity is 96.1%.
Embodiment 3 prepares intermediate compound IV
4 are prepared for raw material, as a example by 5-benzyloxy-2 bromo toluene with intermediate V
To equipped with in 500 milliliters of three neck round bottom flasks of mechanical agitator, add 30.4g intermediate V (0.1mol) and 200 Milliliter dichloromethane, stirring forms solution.Reaction bulb is placed in the cooling bath of acetone and dry ice, is kept stirring for.In half an hour Interior dripping 19.2g bromine (0.12mol) in solution, keeping temperature in reaction bulb during dropping is-70 DEG C～-30 DEG C, drips Bi Hou, removes cooling bath, warms naturally to room temperature.Filtration under diminished pressure, collect solid, drain, obtain purity be 96.4% faint yellow Solid 36.5 grams, productivity is 95.3%.
If with NaBr-Br equimolar with bromine2Replacing bromine, use identical operational approach, obtaining purity is 95.1% Solid 37.1 grams, productivity is 96.1%.
Embodiment 4 prepares intermediate compound IV
4 are prepared for raw material, as a example by 5-benzyloxy-2 bromo toluene with intermediate III
To equipped with in 500 milliliters of three neck round bottom flasks of mechanical agitator, add 66.7g potassium carbonate (0.48mol), centre Body III40.6g (0.2mol) and 250 milliliters of acetone, stir half an hour.60.8g benzyl chlorine (0.48mol) is added in mixture, Being heated to reflux 5 hours, reaction TLC follows the tracks of.After reaction terminates, filtration under diminished pressure, and remove solvent under reduced pressure and obtain solid, then should Solid is poured into water stirring, filtration under diminished pressure, drains, and obtains faint yellow solid 70.3 grams, and productivity is 91.8%.
According to the benzyl bromo of identical mole for benzyl chlorine, using identical method, obtain 70.9 grams of solids, purity is 95.4%.
Embodiment 5 prepares intermediate II
To equipped with in 500 milliliters of three neck round bottom flasks of mechanical agitator, it is initially charged 5.3g intermediate compound IV, 36g magnesium chips (0.15mol), 200mLTHF (oxolane), 0.5g Bromofume, be heated to micro-boiling, more slowly drip remaining intermediate compound IV (33g) THF solution, keeps solution slight boiling condition.After dropping, it is stirred for 1 hour, in mixture, adds 4 equivalents do Ice, stirs 2 hours.In reaction bulb, add the hydrochloric acid of 2N to pH=1, under agitation reactant mixture is poured in frozen water, mistake Filtering to obtain faint yellow solid 30.7 grams, productivity is 88.1%, and purity is 96.4%.
Embodiment 6 prepares target compound I
In 500 milliliters of reaction bulbs, it is initially charged 50g intermediate II (0.144mol), 0.5g5%Pd/C and 200 milliliters different Propanol, is fixed on reaction bulb on rock type catalytic hydrogenation device, after three logical hydrogen exchanges drive the air in bottle away, is passed through The hydrogen of 45psi shakes 2 hours, Filtration of catalyst, and removal of solvent under reduced pressure obtains brown-black solid 23.3 grams.By solid With the hydrochloric acid recrystallization of the ethanol of 150 milliliter 95% and 1 milliliter of 1M, obtaining 22.5 grams of faint yellow solids, purity is 99.3%, produces Rate is 93.6%.
Although the present invention is open the most as above with preferred embodiment, but it is not limited to the present invention, any is familiar with this skill The people of art, without departing from the spirit and scope of the present invention, can do various changes and modification, therefore the protection model of the present invention Enclosing should be with being as the criterion that claims are defined.

Claims (1)

1. prepare 4 for one kind, the method for 5-dihydroxy-2-ar-Toluic acid, it is characterised in that
Described method, specifically:
(1) 2-bromo-4,5-orcin are prepared
To equipped with in 500 milliliters of three neck round bottom flasks of mechanical agitator, add 24.8g 4-methylbenzene-1,2-diphenol and 200 Milliliter dichloromethane, stirring forms solution；Reaction bulb is inserted in the cooling bath of acetone and dry ice, be kept stirring for；In half an hour Inside dripping 38.4g bromine, during dropping, in holding reaction bulb, temperature is-70 DEG C～-30 DEG C, after dropping, removes cooling bath, from So it is warming up to room temperature；Solvent evaporated, recrystallization, filtering, drain, obtain 38.2 grams of products, productivity is 94.2%, and purity is 93.8%；Crude product obtains, through recrystallization from ethyl acetate/petroleum ether, the solid 35.8 grams that purity is 98.1%；Wherein ethyl acetate/stone In oil ether, ethyl acetate is 1:4 with the ratio of petroleum ether；
(2) with 2-bromo-4,5-orcin is that raw material prepares 4,5-benzyloxy-2 bromo toluene
To equipped with in 500 milliliters of three neck round bottom flasks of mechanical agitator, add the potassium carbonate of 66.7g, 40.6g 2-bromo-4,5- Orcin and 250 milliliters of acetone, stir half an hour；In mixture, add 60.8g benzyl chlorine, be heated to reflux 5 hours, reaction Follow the tracks of with TLC；After reaction terminates, filtration under diminished pressure, and remove solvent under reduced pressure and obtain solid, then this solid is poured into water stirring, Filtration under diminished pressure, draining, obtain faint yellow solid 70.3 grams, productivity is 91.8%；
(3) 4,5-benzyloxy-2-methyl-benzoic acid
To equipped with in 500 milliliters of three neck round bottom flasks of mechanical agitator, it is initially charged the 4 of 5.3g, 5-benzyloxy-2-bromine first Benzene, 36g magnesium chips, 200mL oxolane, 0.5g Bromofume, be heated to micro-boiling, more slowly drip the 4 of remaining 33g, 5-bis- The THF solution of benzyloxy-2 bromo toluene, keeps solution slight boiling condition；After dropping, it is stirred for 1 hour, adds in mixture Enter 4 equivalent dry ice, stir 2 hours；In reaction bulb, add the hydrochloric acid of 2N to pH=1, under agitation reactant mixture is poured into In frozen water, filtering to obtain faint yellow solid 30.7 grams, productivity is 88.1%, and purity is 96.4%；
(4) 4,5-dihydroxy-2-ar-Toluic acid is prepared
In 500 milliliters of reaction bulbs, be initially charged the 4 of 50g, 5-benzyloxy-2-methyl-benzoic acid, the 5%Pd/C of 0.5g and 200 milliliters of isopropanols, are fixed on reaction bulb on rock type catalytic hydrogenation device, drive the sky in bottle away through three logical hydrogen exchanges After gas, the hydrogen being passed through 45psi shakes 2 hours, Filtration of catalyst, and removal of solvent under reduced pressure obtains brown-black solid 23.3 Gram；By the solid ethanol with 150 milliliter 95% and the hydrochloric acid recrystallization of 1 milliliter of 1M, obtaining 22.5 grams of faint yellow solids, purity is 99.3%, productivity is 93.6%.
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