[CONTRIBUTION FROM
TEE
RESEARCH LABORATORY OF ARMOUR AND COMPANY ]
OBSERVATIONS ON THE EFFECT OF SOME SOLVENTS UPON T H E ACYLATION OF PHENOL WITH HIGH MOLECULAR WEIGHT ACID CHLORIDES A. W. RALSTON, ALFRED IXGLE,
AND
31. R. McCORKLE
Received June 18, i9@
When phenol is acylated with caprylyl chloride in the presence of aluminum chloride, it has been recently shown (1) that the ratio of para- to ortho-hydroxy ketones produced is materially influenced by the solvent employed. In this previous work the solvents studied were carbon disulfide, nitrobenzene, tetrachloroethane, and a hydrocarbon (petroleum ether, b.p. 60-71", Skellysolve B). The observation was made that carbon disulfide gave the lowest ratio of para- to ortho-hydroxycaprylophenone, while nitrobenzene decidedly favored the formation of the para isomer. It seemed desirable to extend this work to include the influence of solvents during the acylation of phenol with acyl chlorides of higher molecular weight than caprylyl chloride. Previously, it has been shown (1, 2, 3, 4,5 ) that the molecular proportion of aluminum chloride, the order of addition of the reactants, and the temperature are factors which in3uence the relative yield of isomers in both the rearrangement of phenyl esters and in the acylation of phenol. In order to obtain a direct comparison of the orienting effects of the several solvents studied in this work and to exclude other variables, a small excess of aluminum chloride over the amount required to form both the phenol-aluminum chloride and acyl chloride-aluminum chloride complexes was used. Three solvents have been investigated, namely: tetrachloroethane, carbon disulfide, and nitrobenzene. The even-numbered acyl chlorides from caprylyl chloride to stearoyl chloride inclusive were studied. The results of this study, as summarized in Table I, show that when nitrobenzene is used as a solvent for these acylations in the presence of an excess of aluminum chloride the relative yield of para-hydroxy ketones to ortho-hydroxy ketones is much higher than when carbon disulfide is employed. The length of the alkyl chain does not appear t o exert a pronounced influence upon the relative yields of para- and ortho-hydroxy ketones. This is evidenced by the fact that the p/o ratios of the products are comparable over the entire range of acid chlorides. Acylations in tetrachloroethane conducted with acyl halides of higher molecular weight than caprylyl chloride gave resinous products from which no ketones could be isolated. It has been previously shown (6) that good yields of both para- and ortho-hydroxy ketones can be obtained in the acylation of phenol with high molecular weight acyl chlorides when only one molecular equivalent of aluminum chloride is used and tetrachloroethane is employed as the solvent. Furthermore, it is known that when an excess of aluminum chloride is employed in ticylations of phenol using caprylyl chloride the ratio of para- to ortho-hydroxy ketones produced is quite high. The observation, Table I, that acylations with 457
458
RALSTON, INGLE, .4ND MCCORKLE
acyl chlorides of higher molecular weight than caprylyl chloride yield only resins when conducted in tetrachloroethane with an excess of aluminum chloride, indiEFFECTOF SOLVENTS UPON
TABLE I ACYLATIONOF PHENOL IN ALUMINUMCHLORIDE^
THE
THE
PRESENCE OF EXCESS
SOLVENT
Tetrachlorethaneb
ACID CHLORIDE
I
Nitrobenzenec
% Para
'0 Ortho
~
$ :'
68.0 21.5 74.2 20.6 72.5 21.3 72.7 21.1 66.7 21.6 67.1 21.3 a 0.22 mole AlCla, 0.11 mole phenol and 0.1 mole RCOCl. b 3 hrs. a t 70". 0 3 hrs. a t 70". d 5.5 hrs. at 47".
3.16 3.61 3.39 3.44 3.08 3.14
I-
Carbon Disulfided
--
7'% Para
6 Orthc __
Ratio PI0
54.7 52.0 54.6 52.3 50.7
40.8 43.6 41.4 35.6 46.6 41.6
1.34 1.19 1.32 1.47 1.09 1.30
54.0
--
TABLE I1 EFFECT OF ALUMINUM CHLORIDEUPON REAGENTS A N D PRODUCTS IN THE ACYLATION OF PHENOL WITH LAUROYL CHLORIDE:TETRACHLOROETHANE 5 HRS. AT 50" REACTANTS
W O P E T I C A L YIELD
0.22 Mole AlC13 0.11 iMole phenol 0.1 Mole lauroyl chloride 80 cc. Solvent
0 ,p-Hydroxylaurophenones
0.22 Mole AlC13 0.11 Mole phenol 60 cc. Solvent
Phenol 10.4 g .
Phenol 61.5 Resins 14.4
0.22 Mole AICls 0 . 1 Mole lauroyl chloride 60 cc. Solvent
Lauric acid 20.1 g.
Resins 64.2
0.08 &$oleAlC13 0.04 Mole p-hydroxylaurophenone 32 cc. Solvent
p-Hydroxy ketone 11.1 g.
Resins 84.7
o-Hydroxy ketone 8.9 g. 0.0668 Mole AlC13 0.0324 Mole o-hydroxylaurophenone 0.22 Mole 60 cc. Solvent
Solvent 58 cc.
27.6 g.
Resins 70.7
Resins 78.6 Solvent 96.7
cates that this is not a satisfactory solvent for the preparation of high molecular weight para-hydroxy ketones.
ACYLATION OF PHENOL
459
The fact that only resinous products were obtained when acylations with higher molecular weight acid chlorides were conducted in tetrachloroethane under these conditions indicates either that one of the reactants is unstable or that the hydroxy ketones themselves undergo decomposition. It appeared that such reactions may also involve the solvent, since hydroxy ketones were obtained in high yields when carbon disulfide or nitrobenzene was used as the solvent. In order t o investigate further the effect of tetrachloroethane upon these acylations, phenol, lauroyl chloride, and ortho- and para-hydroxylaurophenone were treated with excess aluminum chloride under conditions similar to those employed during the acylation reactions. The effect of aluminum chloride upon tetrachloroethane was also investigated. The results obtained are summarized in Table I1 and show that lauroyl chloride, p-hydroxylaurophenone and o-hydroxylaurophenone form resinous products when heated for five hours a t 50" in the presence of two molecular equivalents of aluminum chloride in tetrachloroethane. Phenol is p:trtially converted to resinous products by this treatment and tetrachloroethane is essentially unaffected. The fact that neither of the hydroxylaurophenones is stable under these conditions is especially noteworthy. There appears to be no plausible explanation a t this time why acylations with acyl chlorides higher than caprylyl chloride in this solvent with excess aluminum chloride yield only resinous products while smooth reactions are obtained with the lower acid chlorides. Hydroxycaprylophenones are stable in tetrachloroethane in the presence of an excess of aluminum chloride but hydroxylaurophenones undergo excessive decomposition. EXPERIMENTAL
Acylation of phenol with lauroyl chloride i n tetrachloroethane. Anhydrous aluminum chloride (29.3 g., 0.22 mole) was weighed into a dry, 200-cc., three-necked flask equipped with a mechanical stirrer, dropping-funnel, and thermometer. Tetrachloroethane (20 cc.) was then added, followed by phenol (10.4 g., 0.11 mole) dissolved in 50 cc. of tetrachloroethane. After the evolution of hydrogen chloride had subsided, lauroyl chloride (21.9 g., 0.1 mole) dissolved in 20 cc. of tetrachloroethane was added dropwise over a period of twenty-five minutes. The mixture was then heated for three hours a t 70" with constant stirring, after which i t was hydrolyzed by pouring into 200 cc. of cold water, and steam distilled to remove the solvent. The product was cooled, transferred to a liter separatory funnel, ether added, and the aqueous layer removed. The ether layer was then extracted with two 100-cc. and two 40-cc. portions of 3% sodium hydroxide in a 10% solution of alcohol in water. The alkaline extract was acidified with hydrochloric acid, boiled to remove the alcohol and ether, and cooled. The oily product was dissolved in ether, placed in a Claisen flask and the ether removed by a water-bath. Vacuum distillation under 4 mm. pressure gave 7.8 g. of a viscous oil boiling up to 240'. The residue was a tar-like product which weighed 5.8 g. The ether solution from the alkali extraction was dried with anhydrous sodium sulfate and the ether removed by evaporation. Distillation of the product under 4 mm. pressure gave an oily product (7.29 g.) and 1.69 g. of a tar-like residue. p-Hydroxylaurophenone could not be identified in the alkali-soluble portion nor o-hydroxylaurophenone in the alkali-insoluble fraction. Similar reactions were run using caprylyl, capryl, myristoyl, palmitoyl, and stearoyl chlorides. Resinous products were obtained in every case with the exception of the caprylyl chloride which gave 49.5% p-hydroxycaprylophenone (m.p. 62-63", 2,4-dinitrophenylhydraxone m.p. 176-176.5') and 21.4% of o-hydroxycaprylophenone (b.p. 115-120" a t 1 mm., 2,4-dinitrophenylhydrazonem.p. 144.5-145').
460
RALSTOK, INGLE, AND MCCORKLE
Acylation of phenol with lauroyl chloride i n nitrobenzene. Anhydrous aluminum chloride (29.3 g., 0.22mole) was mixed with 30 cc. of nitrobenzene, and phenol (10.4 g., 0.11 mole) dissolved in 30 cc. of nitrobenzene was added. Lauroyl chloride (21.9g., 0.1 mole) dissolved in 30 cc. of nitrobenzene was then added dropwise. The reaction mixture was heated for three hours a t 70". The product was hydrolyzed, steam distilled, and the 0- and p-hydroxylaurophenone separated as above described. This yielded 5.9 g. of o-hydroxylaurophenone (m.p. 42.5-43",2,4-dinitrophenylhydrazonem.p. 92-93') and 20.0 g. of p-hydroxylaurophenone (m.p. 70-71", 2,4-dinitrophenylhydrazonem.p. 147-148'. Phenol was also acylated with caprylyl, capryl, myristoyl, palmitoyl, and stearoyl chlorides according to the above procedure. The yields are shown in Table I. The melting points of the hydroxy ketones and of their 2,4-dinitrophenylhydrazonesagreed with those previously reported (6). o-Hydroxycaprophenone and p-hydroxycaprophenone have not been previously described. The melting point of the former is 35.0-35.5' and of the latter 63.5-64.0'. The 2,4-dinitrophenylhydrazonesmelted a t 111-112" and 148-148.5' respectively. Anal. Calc'd for C16H2402: C, 77.37;H , 9.74. Found: (ortho) C,77.14;H, 10.03. (para) C, 77.40;H, 9.75. Acylation of phenol with lauroyl chloride i n carbon disulfide. The acylation was conducted in a manner similar to that previously described with the exception that carbon disulfide was used as the solvent instead of nitrobenzene. The reaction was run for five and onehalf hours a t the reflux temperature of the carbon disulfide. Hydrolysis was accomplished by pouring into water followed by the addition of an equal volume of a mixture of alcohol and concentrated hydrochloric acid. The isomers were separated as described above. Acylations were conducted in a similar manner with caprylyl, capryl, myristoyl, palmitoyl, and stearoyl chlorides. The melting points of the products agreed with those previously reported. Effect of aluminum chloride upon phenol i n tetrachloroethane. Phenol (10.4g., 0.11mole) in 60 cc. of freshly distilled tetrachloroethane was heated for five hours at 50" with anhydrous a!uminum chloride (29.3g., 0.22 mole). The product was hydrolyzed by pouring into water and the aqueous layer separated from the solvent layer. The former was acidified with hydrochloric acid and extracted four times with 50-cc. portions of ether. This ether solution was then dried with anhydrous sodium sulfate. The solvent layer was shaken with two 60-cc. portions of 5% aqueous sodium hydroxide solution and the alkaline extract acidified with hydrochloric acid and extracted with three 50-cc. portions of ether. This ether solution was then dried with anhydrous sodium sulfate and combined with the former ether extract. The ether was then removed and the product distilled a t atmospheric pressure. Effect of aluminum chloride upon lauroyl chloride in tetrachloroethane. Lauroyl chloride (21.9g., 0.1mole) was heated with anhydrous aluminum chloride (29.3g.,0.22mole) in 60 cc. of tetrachloroethane for five hours a t 50". The product was hydrolyzed and the solvent removed by steam distillation. This product was then dissolved in ether and the solution dried. Distillation a t 6 mm. pressure gave only a resinous product, 12.9 g., 64.2%. S o lauric acid was identified either in the distillate or residue. Effect of aluminum chloride upon p-hydroxylaurophenone. p-Hydroxylaurophenone (11.1 g., 0.04 mole) was heated with anhydrous aluminum chloride (10.7 g., 0.08 mole) in 32 cc. of tetrachloroethane for five hours a t 50". After hydrolysis and steam distillation there was recovered 9.4 g., 84.7% of a resinous product from which no p-hydroxylaurophenone could be separated. A similar treatment of o-hydroxylaurophenone gave 78.0% of an oil from which no o-hydroxylaurophenone could be obtained. Effect of aluminum chloride upon tetrachloroethane. Tetrachloroethane, 60 cc., was After hydrolysis heated with 29.3 g. of anhydrous aluminum chloride for five hours at 50'. and steam distillation, 58 cc. (96.7%) of the tetrachloroethane was recovered. Distillation gave only a trace of a brownish residue.
ACYLATION OF PHENOL
461
SUMMARY
1. Friedel-Crafts acylations of phenol have been conducted with even-numbered acyl halides from caprylyl to stearoyl chlorides inclusive in tetrachloroethane, nitrobenzene, and carbon disulfide in the presence of excess aluminum chloride, and the results compared. 2. Nitrobenzene exerts a much greater para-directing influence than carbon disulfide. 3. Acylations of phenol with acyl chlorides of higher molecular weight than caprylyl chloride in tetrachloroethane gave only resinous products. 4. The length of the alkyl chain does not exert an influence upon the ratio of para to ortho isomers obtained when phenol is acylated under the conditions described. (:HICAGO,
ILL.
REFERENCES (1) (2) (3) (4) (5) (6)
RALSTON, MCCORKLE, AND BAUER, J . Org. Chem., 6, 645 (1940). EIJKMAN, Chem. Weekblad, 1, 453 (1904); 2, 59 (1905). ROSENMTJND AND ~ ~ H N U R R Ann., , 460,56 (1928). STOUGHTON, J . Am. Chem. SOC.,67, 202 (1935). RALSTON, MCCORKLE, AND SEGEBRECIIT, J. Org. Chem., 0, 750 (1941). RALSTON AND BAUER, 6.Org. Chem., 6, 165 (1940).
