CN85101149A - The preparation method of N-acyl group-hydroxyl and N-acyl group-acyloxy aromatic amine - Google Patents
The preparation method of N-acyl group-hydroxyl and N-acyl group-acyloxy aromatic amine Download PDFInfo
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Abstract
The invention relates to hydroxyl aromatic ketone (as 4-hydroxy acetophenone) is the method that raw material is produced N-acyl group-hydroxy aromatic amine (as N-acetyl-p-aminophenol (APAP)) and produced N-acyl group-acyloxy aromatic amine (as 4-acetoxyl group Acetanilide (AAA)).Said hydroxyl aromatic ketone is with a kind of aromatic ester (as phenylacetate) or a kind of phenolic compound (as phenol), and a kind of acylating agent (as acetate) is produced to well for raw material.
Description
As everyone knows; N-acyl group acyloxy aromatic amine (for example 4-acetoxyl group Acetanilide) can be by the sodium salt (for example sodium salt of N-ethanoyl p-aminophenol (APAP)) of preparation corresponding N-acyl group hydroxy aromatic amine, this sodium salt and suitable carboxylic acid anhydride (for example diacetyl oxide) are reacted and obtains.Used raw material N-acyl group hydroxy aromatic amine (for example APAP) itself is to be got with acylating agent such as acid anhydrides (for example diacetyl oxide) acidylate by corresponding hydroxy aromatic amine (as p-aminophenol) in the above-mentioned reaction.But back single step reaction may produce some problems: as be difficult to control make hydroxy aromatic amine only carry out monoacylation; The oligomerization of hydroxy aromatic amine; Generation of coloring matter or the like.
In addition, when synthesizing APAP, generally be to make oil of mirbane shortening in the presence of the platinum catalyzer with p-aminophenol, reset simultaneously, generate p-aminophenol.Will reclaim dissolved platinum catalyzer in this reaction is a problem.
Everybody knows that also the preparation of APAP can also obtain the 4-chloroaniline by 4-nitro-chlorobenzene hydrogenation, and 4-chloroaniline and sodium hydroxide reaction then generates p-aminophenol, and the latter becomes N-ethanoyl p-aminophenol through acidylate as mentioned above.This process more complicated needs through several reactions, by several purification steps.The acetylization reaction one of this process step is believed the same problem that is taken place in the time of can being created in the p-aminophenol that acetylize makes by oil of mirbane in addition.
Well-known in the present technique field, hydroxyl aromatic ketone can make by Fu Lisi (Fries) rearrangement reaction of aromatic ester.Louis (Lewis) (United States Patent (USP) 2,833,825) points out, makes catalyzer with anhydrous hydrogen fluoride and can make phenylester or other aromatic ester be rearranged into Acylphenol or other hydroxyl aromatic ketone.Given example is only limited to the rearrangement reaction of high-grade aliphatic ester in this patent, and the productive rate scope is 55～95%.
Xi Mengsi people such as (Simons) is at (the 485th～486 page of (J of 1940 the 62nd volumes of JACS, of Amer.chem.Soc.62.485and 486(1940))) point out, hydrogen fluoride can be used as the condensation reagent of various rearrangement reactions, points out at the 486th page.Can obtain parahydroxyacet-ophenone by phenylacetate through fries' rearrangement.
(series taken in applied chemistry institute of Ai Langgen university of this paper is reported in (Reports from the Ins-titute for Applied Chemistry of the uni versity of Erlangen), receives on January 7th, 1954 one piece of monograph for red (Dann) and Mo Lisi (Mylius).Be published in " chemical record event " 1954 the 587th volume the 1st to 15 page (Annalen der Chemie 587 Band.Pages 1 to 50(1954))) in point out, in the presence of hydrogen fluoride, after reaction in 24 hours, phenylacetate is rearranged into the 4-hydroxy acetophenone, maximum output is 81%, and mention: K. Wei Shete (K.Weichert) and claim and obtain 92% productive rate, this result is at " applied chemistry " nineteen forty-three the 56th volume the 338th page (Ange Wan Chemie 56 338(1943)) on made report., red and Mo Lisi thinks, the difference on the productive rate, to small part be because Wei Shete has ignored the 2-hydroxy acetophenone of generation simultaneously.
Red and Mo Lisi finds that also in the presence of hydrogen fluoride, phenol and glacial acetic acid reaction can generate the 4-hydroxy acetophenone, and productive rate is 61.6%.General this reaction can be considered to not end De-Ke that a phenol makes acetylizing agent with acetate and come Ford (Friedel-Crafts) acetylization reaction.People such as Xi Mengsi are at the 1795th and 1796 page of (Journal of the American Chemical Society of JACS nineteen thirty-nine the 61st volume; 61; 1795 and 1796(1939)) point out in; available hydrogen fluoride makes aromatics generation acylation reaction as condensing agent; in 1796 pages table 1, point out; phenol can generate para hydroxybenzene ketone with the acetate acetylize, and productive rate is 40%.
The German Patent prospectus 2616986((German offenlegungssch-rift 2616986 that Miao Si Deerfu people such as (Meussdoerffer) published on October 27th, 1977) (patent right of this patent transfers Beyer Co., Ltd (Bayer AG))) in, disclose with carboxylic acid halides (as Acetyl Chloride 98Min.) acylation of phenol compounds (as phenol) to prepare the method for hydroxyl aromatic ketone.
Ao Weisi people such as (Auwers) is at the 36th～51 page of (Chemiste Berichte 58 of chemical journal nineteen twenty-five the 58th volume, 36-51, (1925)) point out, Beckmann rearrangement can take place in many kinds of oximes of aromatic ketone (majority is a substituted acetophenone), yet the trial of carrying out rearrangement reaction with the last unsubstituted hydroxyl aromatic ketone of ring only limits to the o-hydroxyacetophenone oxime, as a result, do not obtain amine, i.e. the trial of this rearrangement is success not.See the 41st page of this article.
Gan Bu people such as (Ganboa) is in " synthetic communication " nineteen eighty-threes 13 volume 11 phases the 941st～944 page of (Syn.Communication 13(11) 941-944,1983) point out that Acetanilide can obtain by the oxammonium hydrochloride solution of backflow methyl phenyl ketone.Yet do not propose how to synthesize N-acyl group acyloxy aromatic amine, the scheme of (for example 4-acetoxyl group Acetanilide (AAA)) or N-acyl group hydroxy aromatic amine (for example N-ethanoyl-p-aminophenol (APAP)).
Pearson people such as (Pearson) is content below JACS the 75th volume the 5905th～5908 page (December 5 nineteen fifty-three) discloses: ketone and hydrazine hydrate reaction generation hydrazone, hydrazone become acid amides with Sodium Nitrite and strong sulfuric acid response are rearrangeable again.Particularly people such as Pearson points out that the hydrazone of parahydroxyacet-ophenone can generate hydroxyacetanilide through above-mentioned rearrangement on 5907 pages, i.e. APAP.
A content of the present invention is; producing of N-acyl group-hydroxy aromatic amine (for example N-ethanoyl p-aminophenol (APAP)) is by following process: with hydroxyl aromatic ketone (as 4-hydroxy acetophenone (4-HAP)) and hydroxylammonium salt reaction; generate the ketoxime of this aromatic ketone; and make ketoxime in the presence of catalyzer, carry out Beckmann rearrangement, generate N-acyl group-hydroxy aromatic amine.
In one embodiment; N-ethanoyl-p-aminophenol (APAP) (also claiming ethanamide phenol) is to be raw material with phenylacetate or phenol and acetylizing agent (as acetate); produce by several combined processes; comprising: phenylacetate or phenol and acetylizing agent are become the 4-hydroxy acetophenone through fries' rearrangement or friedel-crafts acetylization reaction respectively, again the 4-hydroxy acetophenone is transformed into corresponding ketoxime with azanol or hydroxylammonium salt.Make ketoxime in the presence of catalyzer, carry out Beckmann rearrangement again, generate N-ethanoyl-p-aminophenol.
Another content of the present invention is; producing of N-acyl group-acyloxy aromatic amine [as 4-acetyl oxygen ethanoyl aniline (AAA)] is by following process: with hydroxyl aromatic ketone [for example 4-hydroxy acetophenone (4-HAP)] and azanol or hydroxylammonium salt reaction; generate the ketoxime of this arone; make ketoxime carry out Beckmann rearrangement; ketoxime is contacted with the Beckmann rearrangement catalyzer with carboxylic acid anhydride, can generate N-acyl group-acyloxy aromatic amine simultaneously with acylation reaction.
In another embodiment; 4-acetyl oxygen ethanoyl aniline (AAA) is raw material with phenylacetate or phenol and acetylizing agent (as acetate) and produces by several combined processes; comprising: come phenylacetate or phenol and acetylizing agent the Ford acetylization reaction to become the 4-hydroxy acetophenone by fries' rearrangement or Fred-Ke respectively; then the 4-hydroxy acetophenone is changed into corresponding ketoxime with azanol or hydroxylammonium salt; ketoxime is by contacting with the Beckmann rearrangement catalyzer with diacetyl oxide; carry out Beckmann rearrangement and acetylize simultaneously, generate 4-acetyl oxygen ethanoyl aniline.
Be raw material when implementing synthetic method of the present invention with the phenylacetate, the initial fries' rearrangement that is generated the 4-hydroxy acetophenone by phenylacetate is undertaken by the equation formula I:
If with phenol and acetylizing agent is raw material, the acetylization reaction of the generation 4-HAP that is then taken place is represented by the equation formula II:
X is that acetylizing agent is removed a residue behind the ethanoyl in the formula.For example X can be a hydroxyl; Acetoxyl group; Or the fontanel element, comprise fluorine, chlorine, bromine or iodine.Used acetylizing agent can be, for example: acetate, diacetyl oxide, Acetyl Chloride 98Min. and acetyl bromide.
Among the present invention, the reaction that generates ketoxime is represented with the equation formula III:
The ketoxime that generates by 4-HAP, i.e. 4-HAP oxime, its formation reaction is undertaken by the equation formula IV:
When needed product was N-acyl group-hydroxy aromatic amine, the Beckman among the present invention was heavy
If the product that needs is APAP, Beckmann rearrangement (V) is undertaken by the equation formula VI:
When needed product was N-acyl group-acyloxy aromatic amine, Beckmann rearrangement among the present invention and acylation reaction were undertaken by equation (VII):
If the product that needs is AAA, undertaken by equation (VIII) with the Beckmann rearrangement of acetylization reaction:
At the equation formula III, in (V) and (VII), Ar
1Be a kind of divalent aryl, its characteristic is not strict with, be advisable but lose the base that encircles last two hydrogen atoms with benzene, naphthalene, biphenyl.These bases can be unsubstituted or its ring hydrogen is replaced by other groups, are for example contained alkyl, alkenyl, alkynyl alkoxy or the acyloxy of 1 to 18 carbon atom; The aralkyl that contains 7 to 18 carbon atoms; Halogens such as chlorine, bromine, iodine; Hydroxyl; Amino; Or group such as thiohydroxy replaces.Ar
1Preferably 1, the 4-phenylene, 2, the 1-naphthylidene, 2, the 6-naphthylidene, 5-phenyl-1, the 2-phenylene, 3-phenyl-1,4-phenylene or 3-methyl isophthalic acid, the 4-phenylene, in the listed Position Number, first digit is ketone carbon atom or the occupied Ar of corresponding group
1On Position Number (when two kinds of position non-equivalences), Ar
1It would be desirable 1, the 4-phenylene.
Each R base can be identical or different in the above-mentioned reaction equation, but all be any monovalent organic radical group, can contain 1 to 18 carbon atom; 1 to 4 carbon atom preferably; R can be for example, to contain alkyl, alkynyl, alkoxyl group, acyl group or the acyloxy of 1 to 18 carbon atom.These groups can be unsubstituted, or quilt is such as chlorine, bromine, iodine, hydroxyl; Amino, thiohydroxy, or aryl replaces.Ar can be to Ar with above-mentioned
1The similar univalent perssad of regulation, just the carbon atom that wherein links to each other with OH changes into hydrogen and linking to each other.In reaction formula III, (V) and (VII), R is preferably identical, and it can be methyl, ethyl, propyl group or normal-butyl, and it would be desirable with later reaction in the methyl that matches of the acetic ester that uses and methyl ketone.For generating oxime, the hydroxyl aromatic ketone of preferentially selecting for use is 4-hydroxy acetophenone (4-HAP), and preferential product is 4-acetoxyl group-Acetanilide (AAA) and N-ethanoyl-amino-phenol (APAP).
The hydroxyl aromatic ketone that is used to generate oxime can be produced by known method.For example available corresponding aroma ester makes through fries' rearrangement by following reaction equation.This formula is the general type of equation formula I, Ar, Ar in the formula
1Same as described above with the regulation of R.
In addition, also phenolic compound and acylating agent can be carried out the friedel-crafts acylation reaction by following equation, generate hydroxyl aromatic ketone, this equation is the general type of equation formula II.
Ar, Ar in the formula
1It has aforementioned implication with R, X for the acylating agent of participating in reaction lose acyl group (
) after residue, such as halogens such as hydroxyl, acyloxy (as acetoxyl group) and fluorine, chlorine, bromine, iodine.The phenolic compound that can adopt is exemplified below: phenol, 1-naphthols, beta naphthal, 2-phenylphenol, 4-phenylphenol and ortho-cresol.The available acylating agent has, for example: paraffinic acid (as acetate and propionic acid), alkane acid anhydrides (as diacetyl oxide and propionic anhydride) and carboxylic acid halides (as acetylfluoride and propionyl fluoride, Acetyl Chloride 98Min. and propionyl chloride, acetyl bromide and propionyl bromide).Though be noted that herein and describe the reaction that contains phenolic compound and acylating agent with the friedel-crafts acylation reaction, this be not finger be exactly reaction mechanism.
Above-mentioned two kinds of the most handy hydrogen fluoride of catalyst for reaction, but known in the art for Fu Lisi and Friedel-Crafts reaction effectively other catalyzer can use, for example: aluminum chloride, zinc chloride or boron trifluoride.
When reacting; can be with aromatic ester or phenolic compound and acylating agent, catalyzer and when with the aromatic ester being raw material and when needing; a kind of reaction additives (as diacetyl oxide or acetate) is added in the corrosion resistant reactor; and with this mixture certain temperature (for example :) at about 20 to about 100 ℃, and certain pressure (for example: be about 50～500 pounds/inch
2(3.4～34 crust)) keep for some time (for example: be about 1/2～4 hour) down.If make catalyzer with HF, the known operative technique of then available those skilled in the art is added to its form with liquid or gas in the reactor.When carrying out this reaction, can use inert gas such as nitrogen that reaction compartment is remained under the desired pressure, and the HF of q.s is contacted with reaction solution.General use excessive HF, for example, every mol in the conversion zone has just been participated in the fragrant ester or the phenolic compound of reaction, with about 7～75 molar HF.If AAA or APAP are needed reaction product,, will be raw material with the phenylacetate then, and, will be raw material then with phenol and acetylizing agent (as acetate) if utilize Fred one gram to come the Ford acylation reaction if adopt Fries rearrangement.In these two kinds of reactions, raw material all is converted into 4-HAP, can by method of the present invention it be become AAA or APAP again.
Hydroxyl aromatic ketone (for example 4-HAP) is converted into N-acyl group-acyloxy aromatic amine (as AAA); or be converted into the finishing of process of N-acyl group-hydroxy aromatic amine (as APAP); be at first to generate ketoxime by reaction formula III and (IV) by hydroxyl aromatic ketone; be about to aromatic ketone and azanol or hydroxylammonium salt (example hydrochloric acid azanol; oxammonium sulfate; two oxammonium sulfates; or phosphatic hydroxylamine) and alkali (as ammonium hydroxide; potassium hydroxide, sodium hydroxide, or lithium hydroxide; the alkali consumption is; for example, every mol azanol adds 1～3 mol alkali) contact, under certain temperature (as 0～60 ℃), keep for some time (as 1～4 hour).Any pressure can, for example, 80 mmhg to 10 a normal atmosphere absolute pressure, (0.1 crust～10.1 crust).This reaction preferably in moisture or pure medium, promptly water and (or) alcohol (as methyl alcohol, ethanol, Virahol) in the presence of carry out.
As discussed above, according to a kind of embodiment of the inventive method, ketoxime can be converted into corresponding N-acyl group-hydroxy aromatic amine by equation (V) and (VI) through Beckmann rearrangement.This process is in certain temperature (as-70～118 ℃) contact reacts for some time (as 10 minutes to 4 hours) with ketoxime and this catalyst for reaction, pressure requires not strict, can get the scope of 80 mmhg to 10 normal atmosphere absolute pressures (0.1 crust～10.1 crust).This rearrangement reaction is preferably in temperature-70 ℃ and is about at 1: 0.001 to 1: 0.1 o'clock to the mole ratio of 40 ℃ and ketoxime and catalyzer and carries out, and the reaction times is about 10 minutes to about 2 hours.Any catalyzer that is used for Beckmann rearrangement all can use, for example: a kind of acid (mineral acid such as sulfuric acid or hydrochloric acid; Organic acid (as trifluoroacetic acid, tosic acid, Phenylsulfonic acid or methylsulfonic acid), acidic ion exchange resin (as sulfonic acid ion exchange resin Amberlyst15 or Nafion501) or the thionyl chloride in liquid sulfur dioxide, ether, ethyl acetate, acetone, tetrahydrofuran (THF) or methylene dichloride.Carry out the thionyl chloride that Beckmann rearrangement preferably is used in the liquid sulfur dioxide and make catalyzer.The carrying out that is beneficial to reaction that have with the N-acyl group of needed product is iced carboxylic acid accordingly can generate hydroxy derivatives usually.There is not strict demand for the total consumption of this ice carboxylic acid, usually, the ketoxime concentration (concentration expressed in percentage by weight) in 2～50% scopes when its consumption will make the reaction beginning.
According to another embodiment of the inventive method, ketoxime can be changed into corresponding N-acyl group-acyloxy aromatic amine by equation (VII) and (VII) through Beckmann rearrangement and the acylation reaction followed.This process is in certain temperature (for example 0～118 ℃) following with suitable carboxylic acid anhydride and Beckmann rearrangement catalyzer contact reacts for some time (as 1 to 4 hour) with ketoxime.As the regulation in the above-mentioned reaction formula, various acid anhydrides all can adopt, but preferably with the alkane acid anhydrides (as diacetyl oxide, propionic anhydride or n butanoic anhydride) that 2 to 4 carbon atoms are arranged.Reaction pressure requires not tight, and desirable 80 mmhg are to the pressure range of 10 normal atmosphere absolute pressures (0.1～10.1 crust).In addition, also as discussed above, any catalyzer that is used for Beckmann rearrangement all can use.With the carrying out that is beneficial to reaction that have of the corresponding ice carboxylic acid of acid anhydrides that uses in the reaction, its consumption can reach the 50%(weight percent of used acid anhydrides).Total usage quantity to the ice carboxylic acid is not strict with, but in most of the cases, the ketoxime concentration when the total consumption of the acid anhydrides that is adopted or acid anhydrides/acid mixture will make the reaction beginning is in about 2～50% scope (concentration expressed in percentage by weight).
Following example is further explained the present invention.
Example 1
This example explanation is made catalyzer with hydrogen fluoride, and the fries' rearrangement by phenylacetate can prepare the 4-hydroxy acetophenone.
The phenylacetates of 40.8 grams (0.3 mol) are put in one 300 milliliters the anti-corrosion nickel-base alloy C of haas troy (Hastelloy) autoclave, with the autoclave good seal, be placed in the dry ice/isopropanol bath, the internal temperature of still be reduced to-45 ℃, about 100 torrs that reduce pressure (0.13 crust).Be no more than under 0 ℃ of condition at temperature in the kettle, add 120 gram (6.0 mol) anhydrous fluoridizing hydrogen.Use then
Gas is adjusted to 0 pound/square inch (1.1 crust) with the interior pressure of still, the material in the stirring tank, and 75 ℃ of heating one hour.Under about 45 ℃ of temperature, hydrogen fluoride is extracted out with 45 fens clock times.Mixture is poured on 25 grams on ice, potassium hydroxide solution neutralization with 45%.Use the ethyl acetate extraction mixture aqueous solution, use the anhydrous magnesium sulfate drying organic phase then, filter the back and boil off solvent, obtain the blackish green solid of 44.0 grams with rotatory evaporator, be equivalent to 99.9% phenylacetate and transform, wherein 94.3% be converted into the 4-hydroxy acetophenone specifically.
Example 2
This example explanation, with hydrogen fluoride make catalyzer, diacetyl oxide is made additive, the fries' rearrangement by phenylacetate prepares the 4-hydroxy acetophenone.
30.6 gram (0.3 mol) diacetyl oxides are joined in 300 milliliters the autoclave of hastelloy C.Autoclave is cooled to-50 ℃, and 5 torrs that reduce pressure (0.007 crust), subsequently, 120 gram (6.0 mol) anhydrous hydrogen fluorides are transferred to the autoclave from steel cylinder.After adding hydrogen fluoride, respectively temperature in the kettle and pressure are adjusted to-50 ℃ and 1.1 crust, under agitation, surpass-23 ℃ adding speed, 81.6 gram (0.6 mol) phenylacetates are added in the autoclave with the temperature that does not make mixture with nitrogen.After adding phenylacetate, material in the still is heated to 50 ℃, and stirred 3 hours, during this period of time the pressure that is produced is approximately 40 pounds/square inch (3.9 crust).Then, discharge hydrogen fluoride with caustic scrubber, the material in the autoclave is poured in about 20 gram ice, the potassium hydroxide with 45% is adjusted to 6.5 with the pH value of mixture, extracts mixture with 75 milliliters of ethyl acetate (3 times).The organic phase anhydrous magnesium sulfate drying filters the back with revolving vaporizer except that desolvating.
In the reaction, the phenylacetate transformation efficiency is 98.1%.Obtain following compounds: phenol, productive rate are 1%; 4-hydroxy acetophenone (4-HAP), productive rate are 82.3%; 2-hydroxy acetophenone (2-HAP), productive rate are 4.3%; 3-hydroxy acetophenone (3-HAP), productive rate are 0.1%; 4-acetoxyl methyl phenyl ketone (4-AAP), productive rate are 3.8%; And 4-(4 '-hydroxy phenyl)-and methyl phenyl ketone (HPAP), productive rate is 0.4%.
Example 3
This example explanation, with hydrogen fluoride make catalyzer, acetate is made additive, the fries' rearrangement by phenylacetate prepares the 4-hydroxy acetophenone.
This example is the method for repetition example 2 basically, and just with 13 gram (0.3 mol) acetate, rather than diacetyl oxide is added to before reactor cooling in the reactor, adds hydrogen fluoride then.The phenylacetate transformation efficiency is 99.0%, and the productive rate of following product is as follows: phenol, productive rate are 3.3%; Acetate, productive rate are 0.8%; 4-HAP, productive rate are 80.8%; 3-HAP, productive rate are 0; 2-HAP, productive rate are 5.8%; 4-AAP, productive rate are 0.38%, and HPAP, productive rate are 0.3%.
Example 4
This example explanation is made acylating agent with acetate, and the friedel-crafts acetylization reaction by phenol prepares 4-hydroxy acetophenone (4HAP).
At room temperature, with phenol (9.4 gram, 0.1 mol) with (acetate (12.0 restrain 0.2 mol) is put into 300 milliliters of hastelloy C autoclaves, and reactor vacuumizes, and is cooled to-20 ℃.Then hydrogen fluoride (100 grams, 0.5 mol) is added in the reactor.Reactor is heated to 80 ℃, and insulation is one hour under temperature of reaction.After reaction finished, cooling reactor to 20 ℃ entered the potassium hydroxide laveur with excessive hydrogen fluoride.Ethyl acetate is added in the material in the reactor potassium hydroxide aqueous solution neutralise mixt with 45%.Isolate the organic phase that obtains, use dried over mgso, revaporization obtains containing the yellow solid of 13.1 gram (0.096 mol) 4-HAP.
Example 5
The explanation of this example generates 4-hydroxy acetophenone oxime by 4-hydroxy acetophenone and oxammonium hydrochloride.
Preparation solution: with 13.6 gram (0.1 mol) 4-hydroxy acetophenones, 7.6 gram (0.11 mol) oxammonium hydrochlorides and 10 gram water are added in 40 milliliters of ethanol.The ammoniacal liquor of 5.0 grams 30% is added in this solution, and reflux is 2 hours then.Boil off ethanol with revolving vaporizer, obtain yellow oil, handle, obtain 15.1 gram (99%) 4-hydroxy acetophenone oximes through extracting.
Example 6
The explanation of this example generates 4-hydroxy acetophenone oxime by 4-hydroxy acetophenone and oxammonium sulfate.
Preparation solution: 20.4 gram (0.15 mol) 4-hydroxy acetophenones and 13.0 gram (0.08 mol) oxammonium sulfates are added in 300 ml waters (70 ℃).16.3 milliliter 30% ammoniacal liquor is added in this solution, and reflux is 0.5 hour then.Obtain the white crystals body of 21.0 gram (92%) 4-hydroxy acetophenone oximes through cooling.
Example 7
The explanation of this example generates 4-hydroxy acetophenone oxime by 4-hydroxy acetophenone and phosphatic hydroxylamine.
Preparation solution: 20.4 gram (0.15 mol) 4-hydroxy acetophenones and 12.9 gram (65.6 millimole) phosphatic hydroxylamines are added in 100 ml waters (70 ℃).16.3 milliliter 30% ammoniacal liquor is added in this solution, and reflux is 0.5 hour then.Obtain the white crystals body of 21.0 gram (92%) 4-hydroxy acetophenone oximes through cooling.
Example 8
Cation exchange resin as catalyst is used in the explanation of this example, by the Beckmann rearrangement of 4-hydroxy acetophenone oxime and the acetylization reaction of association, generates 4-acetoxyl group ethanoyl aniline (AAA).
With the mixture of 3.0 gram (220.0 millimole) 4-hydroxy acetophenone oximes, 3.0 gram Amberlyst15 resins (sulfonic acid ion exchange resin that Rohm and Haas company produce) and 75 milliliters of glacial acetic acids and diacetyl oxide (1: 1) reflux 4 hours in nitrogen.Then, the deionizing exchange resin, vacuum boils off acetic acid/acetic anhydride, obtains the yellow-white crystallization.Crystallization is dissolved in the ethyl acetate, handles with gac and anhydrous magnesium sulfate, and filtering mixt also boils off solvent in rotatory evaporator, obtain the yellow crystal body of 3.4 gram (80.4%) 4-acetyl oxygen ethanoyl aniline (AAA).
Example 9
The explanation of this example is made catalyzer with methylsulfonic acid, by the Beckmann rearrangement of 4-hydroxy acetophenone oxime and the acetylization reaction of association, generates 4-acetyl oxygen ethanoyl aniline (AAA)
With 10 gram (66.2 millimole) 4-hydroxy acetophenone oximes, 1.6 gram (70%) methylsulfonic acids, the solution of 50 gram diacetyl oxides and 100 gram glacial acetic acids reflux 2 hours in nitrogen, solution evaporates on rotatory evaporator, obtains 17.0 gram light brown crystallizations.Recrystallization from water obtains 6.7 gram (52.4%) 4-acetyl oxygen ethanoyl aniline (AAA).Contain 32.0% AAA in the mother liquor.Overall yield is 84.4%.
Example 10
The explanation of this example is with phosphoric acid (H
3PO
4) make catalyzer, by the Beckmann rearrangement of 4-hydroxy acetophenone oxime and the acetylization reaction of association, generate 4-acetoxyl group Acetanilide.
With 100 gram glacial acetic acids, 50 gram diacetyl oxides and 3.6 gram 85%H
3PO
4The logical nitrogen-burst agitation of mixture after 30 minutes, add 10 gram 4-hydroxy acetophenone oximes.Reflux is 1 hour in nitrogen, and cool to room temperature neutralizes with 13% yellow soda ash then.Mixture rotatory evaporator evaporation drying is dissolved in solid in the 200 gram boiling water.Behind the heat filtering, appoint the solution naturally cooling, placement is spent the night.The white crystals that generates is collected, and with the washing of 20 ml waters, [60 ℃/100 mmhg (0.13 crust)] drying is 2 hours in vacuum drying oven.After the drying, obtaining 9.4 gram (73.9%) fusing points is the white crystals of 148～150 ℃ 4-acetoxyl group Acetanilide.Recyclable 0.8 gram AAA and 1.5 gram N-ethanoyl-p-aminophenol (APAP) from mother liquor.
The method of example 8 to 10 is respectively by first and second reactions, also can be used for preparing N-ethanoyl-(4-acetoxy-3-aminomethyl phenyl) amine by acetate o-toluene ester or ortho-cresol and acetate and diacetyl oxide; Prepare N-propionyl (4-propionyloxy phenyl) amine by phenylpropionate or phenol and propionic acid and propionic anhydride; Prepare the positive butyryl radicals of N-(the positive butyryl acyloxy of 4-) amine by butanic acid phenyl ester or phenol and butanic acid and n butanoic anhydride.
N-acyl group-the acyloxy aromatic amine of the present invention's preparation, for example AAA can be used as the monomer that preparation gathers (ester-acid amide) class, they can form anisotropy fusion phase, are suitable for making molded article, as moulded product, fiber and film, as U.S. Patent No. 4,330,457; 4,330,375; 4,341,688; 4,351,918; And 4,355, shown in 132.
N-acyl group-the acyloxy aromatic amine of the present invention preparation, for example AAA can also be hydrolyzed into corresponding N-ethanoyl-p-aminophenol (APAP), and it is one of the most widely used anodyne that can sell of need not writing out a prescription.Following example illustrates this process:
Example 11
With the mixture reflux of 5 gram (25.9 millimole) 4-acetyl oxygen ethanoyl aniline (AAA), 1.4 gram 70% methylsulfonic acids and 50 gram water 1 hour.After the cooling, obtain white crystals, the gas chromatographic analysis of the xln and the aqueous solution shows have 90% AAA to change into N-ethanoyl-p-aminophenol (APAP).
Example 12
Cation exchange resin as catalyst is used in the explanation of this example, by the Beckmann rearrangement of 4-hydroxy acetophenone oxime, generates 4-ethanoyl-p-aminophenol.
With the mixture of 3.0 gram Amberlyst15 resins (sulfonic acid ion exchange resin that Rohm and Haas company produce), 3.0 gram (22.0 millimole) 4-hydroxy acetophenone oximes and 50 milliliters of acetate reflux 2 hours in nitrogen.Then, the deionizing exchange resin, acetate is removed through vacuum distilling, obtains a kind of orange residue.Residue is dissolved in the ethanol, handles, use rotatory evaporator to remove ethanol, obtain 2.9 gram yellow oil, after drying, get 2.0 gram (66.7%) N-ethanoyl-p-aminophenol with gac and anhydrous magnesium sulfate.
Example 13
The explanation of this example is made catalyzer with trichoroacetic acid(TCA), by the Beckmann rearrangement of 4-hydroxy acetophenone oxime, generates N-ethanoyl-p-aminophenol.
With solution reflux in nitrogen of 10 gram (66.2 millimole) 4-hydroxy acetophenone oximes and 75 gram trifluoroacetic acids, remove difluoroacetic acid with rotatory evaporator, obtain 14.7 gram oily matter, oily matter is dissolved in 100 ml waters.Cool off half an hour at 0 ℃, crystallization occurs.Filter and dry this crystallization, get 7.1 gram (71%) N-ethanoyl-p-aminophenol.
Example 14
The explanation of this example in liquid sulfur dioxide, is made catalyzer with thionyl chloride, by the Beckmann rearrangement generation N-ethanoyl-p-aminophenol of 4-hydroxy acetophenone oxime.
At pressure bottle (placing carbonic acid gas/acetone bath to cool off) the 50 milliliters of SO that pack into
2, 0.05 milliliter of SOCl
2With 15 gram 4-hydroxy acetophenone oximes.Remove carbonic acid gas/acetone cooling bath, at room temperature stir the material 1.5 hours in the pressure bottle, extract SO out
2, and from pressure bottle, wash out xln with 50 milliliters of warm water.The NH of dropping 30%
4OH is adjusted to 6.5 to the pH value of slurry water solution.Slurries cool off in ice bath, filter then.Filter the xln of gained, with the washing of 10 ml waters and in vacuum drying oven [60 ℃/100 mmhg (0.13 crust)] dried overnight, make 13.3 white crystals that restrain (88.7%) N-ethanoyl-p-aminophenol, its fusing point is 166.5～170 ℃.
The method of example 12 to 14 also can be used to preparation N-ethanoyl-(4-hydroxy-3-methyl phenyl) amine from acetate o-toluene ester or cresols and acetate; Prepare N-ethanoyl-p-aminophenol from phenylpropionate or phenol and propionic acid; Prepare the positive butyryl radicals-p-aminophenol of N-from butanic acid phenyl ester or phenol and butyric acid.
Example 15
Earlier 250 milliliters pressure bottle is placed in the dry ice/acetone batch and cools off, 50 milliliters the SO(of packing in bottle then passes through vacuum transfer), 0.05 milliliter SOCl
2With 15 gram 4-hydroxy acetophenone oximes.Remove dry ice/acetone batch, at room temperature stirred in the pressure bottle material 1.5 hours.Then, extract SO out
2, and from pressure bottle, wash out xln with 50 milliliters warm water.By dripping dense ammonium hydroxide, the pH value of slurry water solution is adjusted to 6.5.Slurries are cooled off in ice bath, filter then.Filter the crystallization of gained and wash with 10 milliliters of frozen water, and in vacuum drying oven, 60 ℃ of following dry nights, make 13.3 white crystals that restrain N-ethanoyl-p-aminophenol, its fusing point is 166.5～170 ℃.
Example 16
Method therefor and example 15 are basic identical, just wash out xln with tap water (24 ℃) from pressure bottle.And with SOCl
2Consumption be increased to 0.1 milliliter, and the reaction times shortens to 25 minutes.Obtain the white crystal (13.7 gram) of N-ethanoyl-p-aminophenol, its fusing point is 165～169 ℃.
Example 17
The explanation of this example is at SO
2In, make catalyzer with thionyl chloride, preparation 2-methyl-4-hydroxyl-Acetanilide.
Method therefor and example 15 are basic identical, have just used 2-methyl 4-hydroxy acetophenone oxime, and the consumption of oxime reduces to 5 grams, and the consumption of thionyl chloride is increased to 0.5 milliliter, and the reaction times shortens to 1 hour, reacts under room temperature (24 ℃).Obtain the pale brown look crystal (1 gram) of 2-methyl 4-hydroxyl-ethanamide, its fusing point is 122～128 ℃.
Example 18
This example explanation is made catalyzer with thionyl chloride in SO, the Beckmann rearrangement by 2-hydroxy acetophenone oxime prepares the 2-hydroxyacetanilide.
Method therefor and example 15 are basic identical, and just the oxime of usefulness is a 2-hydroxy acetophenone oxime, and the consumption of oxime reduces to 5 grams, and the consumption of thionyl chloride is increased to 2.5 milliliters, and the reaction times shortens to 45 minutes, and temperature of reaction is 30 ℃.Obtain the yellow crystals (3.6 gram) of 2-hydroxyacetanilide, its fusing point is 201～203 ℃.
Example 19
This example explanation is made catalyzer with thionyl chloride in ether, the Beckmann rearrangement by 4-hydroxy acetophenone oxime prepares N-ethanoyl-p-aminophenol.
In one 250 milliliters round-bottomed flasks (reflux exchanger and feed hopper are housed), pack into and be dissolved in the gram of 5 in 50 milliliters of anhydrous diethyl ethers 4-hydroxy acetophenone oxime.Then, splash into the 0.5 milliliter of thionyl chloride solution that is dissolved in 15 milliliters of ether, in reinforced process, want the material in the while stirred flask, reinforced back restir 30 minutes by feed hopper.Remove ether with rotatory evaporator.Use hot water dissolving's solid residue of 25 milliliters again.Be adjusted to about 6.5 with the pH value of ammoniacal liquor, this solution be placed in the ice bath cool off subsequently this solution.The crystallization that filter to form is washed with about 10 milliliters frozen water, is placed on then in the vacuum drying oven 65 ℃ of one nights of drying.Make the brown crystal (1.1 gram) of N-ethanoyl-p-aminophenol, its fusing point is 161～162 ℃.
Example 20
The explanation of this example is made catalyzer with thionyl chloride in ethyl acetate, be the p-aminophenol of feedstock production N-ethanoylization with 4-hydroxy acetophenone oxime.
Method therefor is identical with example 19, has just used ethyl acetate to make solvent, rather than uses ether.Obtain the filbert crystal (1.9 gram) of N-ethanoyl p-aminophenol, its fusing point is 158～161 ℃.
Example 21
The explanation of this example is made catalyzer with thionyl chloride in acetone, be the acetylizad p-aminophenol of feedstock production N-with 4-hydroxy acetophenone oxime.
Method therefor is identical with example 19, has just used acetone to make solvent, rather than uses ether.Obtain the brown crystal (3.7 gram) of N-ethanoyl p-aminophenol, its fusing point is 159～161 ℃.
Example 22
The explanation of this example is made catalyzer with thionyl chloride in tetrahydrofuran (THF), be feedstock production N-ethanoyl-p-aminophenol with 4-hydroxy acetophenone oxime.
Method therefor is identical with example 19, has just used tetrahydrofuran (THF) to make solvent.Rather than use ether.Obtain the pale brown look crystal (2.5 gram) of N-ethanoyl p-aminophenol, its fusing point is 156～158 ℃.
Example 23
The thionyl chloride catalyzer is used in the explanation of this example in methylene dichloride, be feedstock production N-ethanoyl-p-aminophenol with 4-hydroxy acetophenone oxime.
Method therefor is identical with example 19, only is to use methylene dichloride to make solvent, rather than uses ether.Obtain the dun crystal (2.7 gram) of N-ethanoyl p-aminophenol, its fusing point is 152～156 ℃.
Example 24
The thionyl chloride catalyzer is used in the explanation of this example in acetone, under vacuum condition, be feedstock production N-ethanoyl-p-aminophenol with 4-hydroxy acetophenone oxime.
Method therefor is identical with example 19, just makes solvent with acetone, rather than use ether, and is to carry out under vacuum [360 mmhg (0.48 crust)].Obtain the pale brown look crystal (3.6 gram) of N-ethanoyl p-aminophenol, its fusing point is 162～164 ℃.
Example 25
This fact of this example explanation, i.e. it almost is quantitative desired product-N-acyl group-hydroxy aromatic amine that the used method of the present invention can be produced productive rate.
Method therefor is identical with example 16, just also needs the N-ethanoyl p-aminophenol in the filtrate is analyzed, to measure the actual recovery of product.The solid that is recovered to weighs 13.7 grams, also contains 0.7 gram N-ethanoyl p-aminophenol in the filtrate.Therefore, yield reaches 97%.
Claims (12)
1, a kind of method comprises: hydroxyl aromatic ketone is contacted with hydroxylammonium salt and alkali; generate the ketoxime of this ketone; and (i) above-mentioned ketoxime is contacted with the Beckmann rearrangement catalyzer; generate N-acyl group-hydroxy aromatic amine; or above-mentioned ketoxime is contacted with the Beckmann rearrangement catalyzer with carboxylic acid anhydride, generate N-acyl group-acyloxy aromatic amine.
2, the method for claim 1, wherein hydroxyl aromatic ketone is the 4-hydroxy acetophenone, and ketoxime is a 4-hydroxy acetophenone oxime, and N-acyl group-hydroxy aromatic amine is N-ethanoyl-p-aminophenol.
3, method as claimed in claim 2 wherein is in a kind of solvent ketoxime to be contacted with the thionyl chloride of catalytic amount, and solvent for use is selected from sulfurous gas, ether, ethyl acetate, acetone, tetrahydrofuran (THF) and methylene dichloride.
4, method as claimed in claim 3, wherein solvent is a sulfurous gas, and rearrangement is between about-70 ℃ to about 40 ℃ of temperature, and pressure carries out under about 0.1 condition of clinging between about 10 crust.
5, method as claimed in claim 3, wherein hydroxyl aromatic ketone is the 4-hydroxy acetophenone, and ketoxime is a 4-hydroxy acetophenone oxime, and acid anhydrides is a diacetyl oxide, and N-acyl group-acyloxy aromatic amine is a 4-acetoxyl group Acetanilide.
6, method as claimed in claim 5 wherein with the hydrolysis of 4-acetoxyl group Acetanilide, generates N-ethanoyl p-aminophenol.
7, as claim 1,2 or 5 described methods, wherein also comprise: the ester of phenolic compound and carboxylic acid is contacted with the fries' rearrangement catalyzer, generate hydroxyl aromatic ketone.
8, method as claimed in claim 7, wherein the fries' rearrangement catalyzer is a hydrogen fluoride.
9, method as claimed in claim 8, wherein ester is a phenylacetate.
10, as claim 1,2 or 5 described methods, wherein also comprise: phenolic compound is contacted with Friedel-Crafts catalyst with acylating agent, generate hydroxyl aromatic ketone.
11, method as claimed in claim 10, wherein Friedel-Crafts catalyst is a hydrogen fluoride.
12, method as claimed in claim 11, wherein phenolic compound is a phenol, acylating agent is an acetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN85101149.7A CN1006068B (en) | 1984-06-04 | 1985-04-01 | Process for producing n-acyl-hydroxy and n-acyl-acyloxy aromatic amines |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US61698984A | 1984-06-04 | 1984-06-04 | |
| CN85101149.7A CN1006068B (en) | 1984-06-04 | 1985-04-01 | Process for producing n-acyl-hydroxy and n-acyl-acyloxy aromatic amines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN85101149A true CN85101149A (en) | 1987-01-17 |
| CN1006068B CN1006068B (en) | 1989-12-13 |
Family
ID=24471841
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN85101149.7A Expired CN1006068B (en) | 1984-06-04 | 1985-04-01 | Process for producing n-acyl-hydroxy and n-acyl-acyloxy aromatic amines |
Country Status (4)
| Country | Link |
|---|---|
| CN (1) | CN1006068B (en) |
| DD (1) | DD238228A5 (en) |
| YU (1) | YU45722B (en) |
| ZA (1) | ZA854178B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108191651A (en) * | 2018-02-02 | 2018-06-22 | 长治学院 | The preparation method of the visible light catalytic phenol acylation reaction synthesis phenolic ester of thiocarboxylic acid mediation |
| CN113777204A (en) * | 2021-07-30 | 2021-12-10 | 河北广祥制药有限公司 | Detection method of p-hydroxyacetophenone related substances |
-
1985
- 1985-04-01 CN CN85101149.7A patent/CN1006068B/en not_active Expired
- 1985-06-03 ZA ZA854178A patent/ZA854178B/en unknown
- 1985-06-03 DD DD27697785A patent/DD238228A5/en not_active IP Right Cessation
- 1985-06-04 YU YU94185A patent/YU45722B/en unknown
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108191651A (en) * | 2018-02-02 | 2018-06-22 | 长治学院 | The preparation method of the visible light catalytic phenol acylation reaction synthesis phenolic ester of thiocarboxylic acid mediation |
| CN108191651B (en) * | 2018-02-02 | 2020-10-30 | 长治学院 | Preparation method for synthesizing phenolic ester through thiocarboxylic acid mediated visible light catalytic phenol acylation reaction |
| CN113777204A (en) * | 2021-07-30 | 2021-12-10 | 河北广祥制药有限公司 | Detection method of p-hydroxyacetophenone related substances |
| CN113777204B (en) * | 2021-07-30 | 2022-07-12 | 河北广祥制药有限公司 | Detection method of p-hydroxyacetophenone related substances |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1006068B (en) | 1989-12-13 |
| YU45722B (en) | 1992-07-20 |
| ZA854178B (en) | 1987-02-25 |
| DD238228A5 (en) | 1986-08-13 |
| YU94185A (en) | 1988-02-29 |
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