CA1298316C - Process for producing 4-hydroxyacetophenone - Google Patents

Abstract

Abstract A process of acetylating phenol to 4-hydroxyacetophenone by contacting phenol with about 0.9 to 1.4 moles of acetic acid per mole of phenol as acetylating agent in the presence of about 20 to 50 moles of hydrogen fluoride per mole of phenol as catalyst at a temperature of reaction of about 40 to 90°C for a reaction period of about 10 to 120 minutes. The process generally results in phenol conversions of at least about 80% and reaction selectivities to 4-hydroxyacetophenone of at least about 70%.

Description

~ 316 71529-6 This invention relates to a process for produeing 4-hydroxyacetophenone.
BACKGROUND OF THE INVENTION
4-Hydroxyacetophenone (4-HAP) is a possible inter-mediate for a variety of products having a multiplicity of end uses. Thus, pending Canadian applieation Serial ~o. 479,446, discloses a process for using 4-HAP to make N-acetyl-para-aminophenol (APAP), better known as acetaminophen, which has wide use as an analgesic. Pending Canadian application Serial No. 479,446, also discloses the use of 4-HAP as an intermediate for the produetion of 4-aeetoxyaeetanilide (4-AAA) which ean be used for the preparation of poly(ester-amide)s capable of forming an anisotropic melt phase and suitable for being formed into shaped articles sueh as moldings, fibers and films. In addition, 4-AAA may also be hydrolyzed to form APAP. Pending Canadian application Serial No. 486,113, discloses a proeess wherein 4-HAP is used to produce 4-acetoxybenzoic acid (4-ABA) which is also capable of being used directly to make polymers whieh ean be formed into an anisotropie melt suitable for the formation of shaped artieles. Moreover, 4-ABA ean be hydro-lyzed to 4-hydroxybenzoie aeld (4-HBA) whieh ean be used as an 129~316 71529-6 intermediate for the production of preservatives, dyes, and fungicides. Pending Canadian applications Serial No. 491,528, and Serial ~o. 498,418 disclose processes wherein 4-HAP is used as an intermediate for the production of hydroquinone (HQ) which has utility as a photographic developer, polymerization inhibitor, dye intermediate, and anti-oxidant.
Dann and Mylius in a dissertation included as part of a series of Reports from the Institute for Applied Chemistry of the University of Erlangen, received for publication on January 7, 1954 and published in Annalen der Chemie 587 Band, pages 1 to 15, disclose the reaction of phenol and glacial acetic acid in the presence of hydrogen fluoride to produce 4-hydroxyacetophenone (4-HAP) in a ~ield of 61.6%. This reaction may be conventionally characterized as a Friedel-Crafts acetylation of phenol with acetic acid as the acetylating agent.
Simons et al, Journal of the American Chemical Society, 61, 1795 and 1796 (1939) teach the acylation of aromatic compounds using hydrogen fluoride as a condensing agent and in Table 1 on page 1796 show the acetylation of phenol with acetic acid to produce p-hydroxyacetophenone (4-HAP) in 40% yield.
~uropean Patent Publication No. 69,597, published January 12, 1983, discloses the preparation of p-phenoxybenzoyl compounds by reacting diphenyl ether and an appropriate acyl compound such as acetic anhydride in the presence of hydrogen fluoride.
Meussdoerffer et al, German Offenlegungsschrift 26 16 986, published October 27, 1977 and assigned to Bayer AG, .

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disclose the hydrogen fluoride-catalyzed acylation of phenolic compounds such as phenol itself with an acyl halide such as acetyl chloride to form hydroxy aromatic ketones.
SUMMARY OF THE INVENTION

.
In accordance with this invention, 4-hydroxyaceto-phenone (4-HAP) is produced by the Friedel-Crafts acetylation of phenol with acetic acid using hydrogen fluoride as catalyst, under certain specified reaction conditions so as to obtain unexpectedly high conversions of phenol and high selectivity to 4-HAP, concurrently.
The preparation of 4-HAP by the acetylation of phenol with acetic acid using hydrogen fluoride as catalyst proceeds in accordance with the following equation:

HO ~ + CH3COOH HF > HO ~ O r C-CH3 + H2O

In carrying out the reaction so as to obtain particu-larly high yields of 4-HAP within this invention, phenol is reacted with about 0.9 to 1.4 moles, preferably about 1.0 to 1.25 moles of acetic acid per mole of phenol at a temperature of reaction of about 40 to 90C, preferably about 50 to 80C in the presence of hydrogen fluoride catalyst in an amount of about 20 to 50 moles, preferably about 25 to 30 moles per mole of phenol for a reaction period of about 10 to 120 minutes, preferably about 30 to 75 minutes.
Using a corrosion-resistant reactor, the reaction is initiated by either: 1) charging hydrogen fluoride to a mixture of phenol and acetic acid at a temperature less than ~2~3~L6 the specified reaction temperature; 2) charging acetic acid to a solut~on of phenol and hydrogen fluoride at reaction temperature; or 3) charg.ing acetic acid and phenol simultaneously to hydrogen fluoride at reaction temperature.
Regardless of the method of initially mixing the acetic acid, phenol, and hydrogen fluoride, the reaction is then adjusted to the specified reaction temperature for the specified reaction period. The hydrogen fluoride may be charged as a liquid or a gas using technologies of handling well known to those skilled in the art. In carrying out the reaction, an inert gas such as nitrogen may be used to keep the reaction space under the desired pressure, about 2.5 to about 500 p5ig., thereby keeping sufficient HF in contact with the reacting liquid.
In general, the process of this invention results in a conversion of phenol of at least about 80%, preferably at least about 90%, with a selectivity to 4-hydroxyacetophenone (4-HAP) of at least about 70~, preferably at least about 80~.
The process is capable of producing relatively high yields of 4-hydroxyacet~phenone using relatively low ratios of hydrogen fluoride to phenol and low temperatures of reaction.
This in turn results in a more economical purification of product and recycle of hydrogen fluoride, and an energy saving due to the low reaction temperatures which are employed.
DESCRIPTION OF SPECIFIC EMBODIMENTS
The following examples illustrate the process of this invention. The term "molar equivalent~ as used in these examples denotes moles of the specified reactant per mole of phenol.

li Example 1 ~Z~31~ 71529-6 A 300 cc Hastelloy C autoclave was cooled to 30 C
using a carbon dioxide/isopropanol bath, and then evacuated to ca 175 Torr. To the autoclave was added 75 g (3.75 mol, 30 molar equivalents) of anhydrous hydrogen fluoride. The contents of the autoclave were heated to 80C whereupon 11.75 g (0.125 mol) of phenol and 7.5 g tO.125 mol, 1 molar eqyivalent)) of acetic acid were simultaneously added over a 1-2 minute period. An exotherm resulted; the internal temperature of the autoclave was lowered to 80C and was maintained at that temperature for 60 minutes with stirring.
The hydrogen fluoride was then vented through a caustic scrubber while simultaneously using a nitrogen purge. The contents of the autoclave were then poured onto ice and the pH
of the resulting aqueous phase was adjusted to 6.0 using a solution of 45% potassium hydroxide. The aqueous phase was extracted with 75 mL of ethyl acetate (3x). The organic extracts were combined, dried over anhydrous magnesium sulfate, and the solvent was removed on a rotary evaporator to yield a crystalline product. The reaction proceeded with 81.9% conversion of phenol and with the indicated selectivities to phenyl acetate (0.4%), 4-hydroxyacetophenone (83.7~ -hydroxyacetophenone (9.4%), and 4-acetoxyacetophenone (0.1%).
Example 2 The procedure o~ Example l was repeated, but employing 50 molar equivalents of anhydrous hydrogen fluoride, and 1.1 molar equivalents of acetic acid. The reaction proceeded with 99.3% conversion of phenol and with the indicated selectivities to 4-hydroxyacetophenone (85.9%), *Tr~e ~ark 5 ~2~'31~

2-hydroxyacetophenone (7.9%), and 4-acetoxyacetophenone (O 1%) -Example 3 The procedure of Example 1 was repeated, but employ-ing 1.25 molar equivalents of acetic acid and a reaction temperature of 73 + 2C. The reaction proceeded with 99.3%
conversion of phenol and with the indicated selectivities to 4-hydroxyacetophenone (80.2%), 2-hydroxyacetophenone (7.1~), and 4-acetoxyacetophenone (0.1%).
Example 4 The procedure of Example 1 was repeated, but employ-ing 1.25 molar equivalents of acetic acid and a reaction temperature of 50 + 2C. The reaction proceeded with 93.8%
conversion of phenol and with the indicated selectivities to 4-hydroxyacetophenone (90.3%), 2-hydroxyacetophenone (4.6%), and 4-acetoxyacetophenone (0.1%).
Example 5 The procedure of Example 1 was repeated, but employ-ing 1.1 molar equivalents of acetic acid. The reaction proceeded with 97.1% conversion of phenol and with the indica-ted selectivities to 4-hydroxyacetophenone (80.3%), and 2-hydroxyacetophenone (8.3%).

Claims (6)

1. A process comprising acetylating phenol with about 0.9 to 1.4 moles of acetic acid per mole of phenol as acetylat-ing agent in the presence of about 20 to 50 moles of hydrogen fluoride per mole of phenol as catalyst, at a temperature of reaction of about 40 to 90°C for a reaction period of about 10 to 120 minutes, to produce 4-hydroxyacetophenone.

2. The process of claim 1 wherein a phenol conversion of at least about 80% and a reaction selectivity to 4-hydroxy-acetophenone of at least about 70% are obtained.

3. The process of claim 1 wherein about 1.0 to 1.25 moles of acetic acid per mole of phenol are employed.

4. The process of claim 3 wherein about 25 to 35 moles of hydrogen fluoride per mole of phenol are employed.

5. The process of claim 4 wherein said temperature of reaction is about 50 to 80°C and said reaction period is 30 to 75 minutes.

6. The process of claim 5 wherein the phenol conversion is at least about 90% and the selectivity to 4-hydroxyaceto-phenone is at least about 80%.