Benzophenones from Carboxylic Acids In the Friedel and Crafts condensation
analogous condensation of acid chlorides, the formation of ortho- and para-isomeric benzophenones is established. In the ammonolysis of halogenobenzophenones the presence of copper is desirable in order to obtain satisfactory amination rates. Under suitable conditions in the amination of 44'dichlorobenzophenone, it is possible to effect the replacement of only one halogen.
of a number of aromatic carboxylic acids, a study of the effect of time, solvent ratio, and aluminum chloride ratio on yield and purity is reported. The condensation of benzoic acid, 4-chlorobenzoic acid, 4methylbenzoic acid, and terephthalic acid with chlorobenzenes is accomplished, with practically theoretical yields. As in the
H. P. NEWTON
AND
P. H. GROGGINS
Color and Farm Waste Division, Bureau of Chemistry and Soils,
Washington, D. C.
N A PRELIMINARY report from this division, Groggins, Nagel, and Stirton (5) showed that carboxylic acids could be condensed with aromatic compounds to produce alkylaryl and diary1 ketones. Their survey showed that the employment of carboxylic acids is of wide application. The present investigation relates to a more detailed study of the preparation of some benzophenones, as well as the amination of typical halogenated derivatives.
Preparation of Dichlorobenzophenones from 4-Chlorobenzoic Acid and Chlorobenzene Dittrich (2) reported the preparation of 4,4'-dichlorobenzophenone from 4-chlorobenxoyl chloride and chlorobenzene in the presence of aluminum chloride in carbon disulfide. Norris and Green (8) and later Norris and Twieg (9) condensed carbon tetrachloride with chlorobenzene. The dichlorodiPhenYl-~,~'-dichloromethaneswere converted by concentrated sulfuric acid to dichlorobenzophenones. They obtained two ketones, the 4,4'-dichlorobenzophenone and the 2,4t~dichlorobenzophenone, with an over-all yield of 73,5 per cent. Norris and Twieg (9) also condensed 2-chlorobenzoyl chloride with chlorobenzene and obtained 2,4'-dichlorobenzophenone. Montagne (6, 7) and his associates obtained both the 4,4'- and 2,4'-dichlorobenzophenones from 4-chlorobenzoyl chloride and chlorobenzene. The 4-chlorobenzoic acid used in this study was obtained from two sources: (1) by the fission of 4'-chloro-2-benzoylbenzoic acid, and (2) by the oxidation of 4-chloroacetophenone. The fission of the 4'-chloro-2-benzoylbenzoic acid was accomplished according to a modification of a patent (3) by intimately mixing 52.1 grams (0.2 mole) of 4'-chloro-2-benzoylbenzoic acid with 24 grams (0.43 mole) of calcium oxide
and 15 grams of water. The flux was heated a t 325" C. for 15 minutes. After cooling, the mass was ground, extracted with a solution of sodium carbonate, and filtered. The filtrate was acidified with dilute hydrochloric acid, which threw down a mixture of 4-chlorobenzoic acid and benzoic acid. The precipitate was collected on a filter, washed with hot water t o remove any benzoic acid, dried, and weighed. The yield was 29 grams or 92.6 per cent of theory. The product melted a t 239' to 240' C., and gave a neutralization equivalent corresponding to a molecular weight of 157 (theoretical neutralization equivalent = 156.5). Liquid-phase oxidation of 4-chloroacetophenone obtained by the Friedel and Crafts condensation of acetic acid with chlorobenzene was carried out according to the following procedure: Into a three-necked flask provided with a reflux condenser, there were introduced 40 grams of 4-chloroacetophenone, 200 acid, grams Of glacial acetic acid, 70 grams Of 50 per cent and then, drop by drop, 120 grams of chromium trioxide in 115 grams of water. The reactants were then heated at the reflux temperature of the mixture for three hours. The contents of the flask were diluted with 500 CC. Of water and cooled t o 25-30' c., and the 4-chlorobenxoic acid was collected on a filter. A yield of 38.5 grams or 95 per cent of theory was obtained. The abid melted at 238O t o 2420 c.,and from its neutralization equivalent a molecular weight of 157 was indicated.
C. E. Senseman and J. J. Stubbs, of this Division, have prepared 4-chlorobenzoic acid by catalytic air oxidation of 4-chloroacetophenone. It is contemplated that a report of this procedure will appear in a subsequent publication. Recrystallization from ethanol of the 4-chlorobenzoic acid from either of the above-mentioned sources yieldedin each case a material melting a t 242.5' to 243' C. This product was employed in the following research. Preliminary experiments indicated that a reaction temperature of about 132' C., corresponding to the boiling point 1397
INDUSTRIAL AND ENGINEERING CHEMISTRY
1398
of chlorobenzene, was necessary to carry the condensation of 4-chlorobenzoic acid with chlorobenzene to approximate completion in a period of 5 to 7 hours, and this temperature was subsequently employed. The reactions were carried out in Pyrex glass flasks fitted with reflux condensers. The flasks were charged with the materials (Table I), heated for the period of the reaction, allowed to cool t o room temperature, and then discharged into dilute cold sulfuric acid. The excess of solvent was removed by steam distillation, after which the residue was collected on a filter and washed free of mineral acid. The crude dichlorobenzophenones were then treated with a hot solution of sodium hydroxide t o remove any unconverted carboxylic acid. The residue was then collected on a filter, washed, dried, and weighed. The separation of the isomeric dichlorobenzophenones was effected by taking advantage of their difference in solubility in ethanol. By dissolving one part of crude material in twenty-five parts by weight of boiling ethanol and then by progressively diluting with water, the 4,4'-dichlorobenzophenone was thrown out, and the 2,4t-dichlorobenzophenoneremained in solution in the ethanol-water mixture as long as the ethanol content was not less than 60 to 65 per cent. The material obtained from 95 per cent ethanol, upon cooling and before dilution, was pure 4,4'-dichlorobenzophenone. In all condensations the product obtained consisted of two isomers; the distribution, on the basis of a theoretical yield, was approximately 80 t o 85 per cent 4,4' dichlorobenzophenone and 10 to 15 per cent 2,4'-dichlorobenzophenone. Results of a study of the effect of time, solvent ratio, and quantity of aluminum chloride are set forth in Table I. It is evident that a solvent ratio of between 3 to 6 moles of chlorobenzene to 1 mole of 4-chlorobenzoic acid is satisfactory. It is also evident that a molar ratio of 3 to 1 of aluminum chloride to 4-chlorobenzoic acid is required t o give yields of as much as 95 per cent of theory, under these conditions of operation. The data also show that when the ratio of aluminum chloride to 4-chlorobenzoic acid is less than 3 to 1, a longer time is required and the yields obtained are not as great. The method of Dittrich (W),involving preparation of the oxime, a Beckmann rearrangement, and finally fission of the anilide, was employed to establish the positions of the halogen atoms in the 4,4' -dichlorobenzophenone. Since this procedure was used to establish the structure of other ketones, it is outlined schematically as follows: 0
C l ~ - b C ) C l 4,4'-Dichlorobenzophenone (melting point = 148' C.) N-OH
NHz.OH*HCl+KOH
Concentrated HISOl
+ CzHsOH
~
4,4'-Dichlorobenzophenone oxime (melting point = 136-136.5' c.)
O H
Alcoholic KOH
(100' C. in autoclave)
C l ~ - % k - C ) C l
-
4,4'-Dichlorobenzanilide
(melting point = 213-213.5' C.)
-
0
ClO-b-OH 4-Chlorobenzoicacid (melting point = 243' C.)
+
C
I
L
~
i
N
H
~
4-Chloroaniline (melting point = 70" C.)
VOL. 27, N O . 12
35.66 grams (82.35 per cent of theory) of 4-chlorobenzophenone, 5.15 grams (11.9 per cent of theory) of 2-chlorobenzophenone, and 1.41 grams (3.25 per cent of theory) of unseparated isomeric ketones. The total yield was 42.22 grams or 97.5 per cent of theory. The melting point of the recrystallized materials was 78.4' C. for 4-chlorobenzophenone, and 45.5' to 46" C. for 2-chlorobenzophenone.
Preparation of 4-Chloro-4'-methylbenzophenone 4-Methylbenzoic acid (p-toluic acid) was condensed with chlorobenzene under the conditions previously described. Two-tenths mole of 4-methylbenzoic acid yielded 37.57 grams (81.5 per cent of theory) of 4-chloro-4'-methylbenzophenone, 5.02 grams (10.9 per cent of theory) of 2-chloro-4'-methylbenzophenone, and 1.67 grams (3.6 per cent of theory) of unseparated isomeric ketones. The total yield was 44.26 grams, or 96 per cent of theory. The pure 4-chloro-4'-methylbenzophenone melted a t 128.5' to 129' C., and the pure 2-chloro4'-methylbenzophenone melted a t 99.5' C. Preparation of Asymmetric Dichlorobenzophenones Satisfactory yields of dichloroketones were obtained by the reaction of 0.2 mole of benzoic acid with 0.8 mole of 1,2-dichlorobenzene and 0.6 mole of aluminum chloride for 5.5 hours a t 130' to 132' C. From an ethanol solution of the dichloroketones obtained in the above-mentioned reaction, there were isolated 39.91 grams (79.5 per cent of theory) of 3,4-dichlorobenzophenone, 5.52 grams (11 per cent of theory) of 2,3dichlorobenzophenone, and 2.26 grams (4.5 per cent of theory) of the unseparated isomeric ketones. The total yield was 47.69 grams, equivalent to 95 per cent of theory. The purified 3,4-dichlorobenzophenonemelted a t 104' to 104.5' C. The oxime melted a t 153' to 154' C. The anilide, upon degradation, gave 3,4-dichlorobenzoic acid (melting point 207' to 208' C.) and aniline. When the 2,3-dichlorobenzophenone was submitted to a similar series of reactions, some 2,3-dichlorobenzoic acid melting a t 166' to 167' C. was isolated. This was considered to be satisfactory evidence of the presence of the isomeric 2,3-dichlorobenzophenone. Condensation of Terephthalic Acid The condensation of terephthalic acid with chlorobenzene did not proceed satisfactorily when the reaction was carried out in an open system, because the boiling point of chlorobenzene is below the effective condensation temperature of terephthalic acid. When, however, 0.1 mole of terephthalic acid reacted with 1 mole of 1,2-dichlorobenzene and 0.6 mole of anhydrous aluminum chloride for 5.5 hours a t 175' to 180' C., 41.5 grams (97.8 per cent of theory) of the isomeric tetrachlorobenzoylbenzophenones were obtained. From this mixture 35.6 grams of a compound melting a t 253' were obtained by extraction with ethanol, the purity of which was not improved by repeated recrystallization. The oxime melts a t 210' C. The anilide made from the oxime by rearrangement melted a t 288'. The degradation of the anilide yielded only two isolable compounds, terephthalic acid (neutralization equivalent 167) and 3,4-dichloroaniline, melting a t 69' to 71 ". These results establish the structure as 3,3", 4,4"-tetrachloro-4'-benzoylbenzophenone :
Preparation of 4-Chlorobenzophenone When 0.2 mole of benzoic acid was reacted with 1 mole of chlorobenzene and 0.6 mole of anhydrous aluminum chloride for 5.5 hours at the reflux temperature of the mixture, condensation was practically complete. There were obtained
35.6 grams of this isomer is equivalent to 84 per cent of theory. There are two other possible isomers, but no attempt was made to isolate them from the residue (5.6 grams).
DECEMBER, 1935
INDUSTRIhL AND ENGINEERING CHEMISTRY
1399
TABLEI. PREPARATION OF DICHLOROBENZOPHENONES 4-Chlorobenaoic acid 31.3grams = 0.2mole Temperature = refldx temperature of chlorobenzene Solvent = excess of chlorobenzene = 0.2 mole X ratio Molar Molar Ratio Ratio ChloroExpt. AlClr: benzene : No. R-COOH Time R-COOH 4,4'-Dichlorobenaophenone
-
Theoretical yield 50.2grams & I , p. of 4,4'-dichlorobenaophenone= 148' C. 31.p. of 2,4'-dichlorobenzophenone = 66.5-67OC.
2,4'-Dichlorobenaophenone
Ketones Unseparateda
Ketones. Total Yield
T.
% of P., % of M . P.. % of % of Houra Grams theory C. Grams theory C. Grams theory Grams theory 12.35 62-3 1.75 3.48 82.47 148 6.20 49.35 98.30 6:l 41.40 3:l 5.5 12.55 62-3 1.53 6.30 3.05 49.33 98.27 82.67 148 3:l 5.5 5:l 41.50 12.15 62-3 1.70 148 6.10 3.39 49.00 82.07 97.61 3:l 5.5 4:l 41.20 82.07 148 6.20 12.35 62-3 1.81 3.61 49.21 98.03 3:l 41.20 3:l 5.5 10.98 148 5.51 62-5 1.61 82.27 1.21 47.42 94.46 5:l 41.30 5 2.75:l 5.5 62-4 1.54 6.20 12.35 3.07 49.14 82.47 148 97.89 6 3.25:l 5.5 5:l 41.40 4.67 9.29 62-3 1.63 8.25 40.80 81.26 68.72 147-8 7 2.2:l 5.5 4:l 34.50 62-3 1.64 3.27 5.10 10.16 44.20 88.05 8 2.2:l 11.0 4:l 37.46 71.62 148 9.86 62-4 1.50 4.95 5.5 4:l 36.63 72.96 147-8 3.00 43.08 9 2.5:l 85.82 10 2.5:l 15.0 4:l 38.20 76.09 148 5.44 10.83 62-3 1.56 3.11 45.20 90.01: a The mixture was converted t o oximes rearranged t o anilides, and then broken down by alcoholic potassium hydroxide under pressure. T h e only products isolated were 2-chlorobenzoic acid, 4-chldrobenaoic acid, and 4-chloroaniline. The isolation of these compounds indicated t h a t the mixture was essentially 2,4'-dichlorobenzophenone and 4,4'-dichlorobenzophenone. 1 2 3 4
TABLE11.
h l I S A T I O N O F 4,4'-DICHLOROBEXZOPHENONE
Aqueous ammonia (28 per cent "I), 315 grams = 5.19moles M. p. of 4,4'-diaminobenaophenone = 245-246' C . M . p. of 4-amino-4'-chlorobenzophenone= 185' C. Copper Expt. 4,4'DichloroMolar ---OxidantsNo. benzophenone Form equivalent NHaNOz HClOa
Autoclave volume = 500 cc. Time = 30 hours Mol. weight of 4,4'-diaminobenzophenone = 212
--.
I -
Mole 0 05 0 05 0 05 0 05 0 05
9 10 11 12 13
0 05 0 05 0 05 0 20
0.20 0 20 0 20
0.20
... C'UO CUO cuo
o:Ois
CUO CUO CUO CUO CUO CUO
0'028
..
0.02s
0.028
...
0.02s 0.028 0.056 0,056 0.056
Grams
Grams
6:OO 6.00
0:75 0.75 0.75
6:OO
0:75
6.00
..
.. .. .. 6:OO
..
Temp.
C. 180
180 180 180 180 200 200 200 200
1:25 0:75 0.75
Amination of 4;E'-Dichlorobenzophenone
The experiments carried out on the amination of 4.4'-dichlorobenzophenone were primarily to determine satisfactory conditions for the preparation of the 4,4'-diaminobenzophenone, and also for the 4-amino-4'-chlorobenzophenone. Britton and Bryner (1) have prepared the diamine from the 4,4'dichlorobenzophenone, obtaining a yield of 72.5 per cent after purification. A somewhat detailed description of the apparatus is given by Groggins and Hellbach (4). The data in Table I1 show the effect of temperature, of varying amounts of copper and of potassium chlorate upon the yield and purity of the amination product. It is evident that a t the lower oDerating ternDerature-i. e., 180" C.-the introduction of the-copper-cataiyst exerts a more marked influence than at 2oo" Since an Of 20" in Operating temperature was accompanied by an increase in noncatalytic amination from 31.6 to 61.9 per cent, it is clear that, as the operating temperature is raised, less copper is required to insure comdete amination. Addition of Potassium chlorate appears to have a beneficial effect only when the ratio of copper to halogen is below a certain minimum. The product from experiment 7, where no catalyst was used, was dissolved in dilute hot hydrocholoric acid and allowed to cool. The precipitate formed was collected on a flter and washed with alkali. It was found to be essentially 4-amino4'-chlorobenzophenone, the diamine remaining in the hydrochloric acid solution. The product melted at 185Oto 185.5OC.
200 200 200
200
--
Gross Yield--% of Grams theory 11.986 113.00 12.192 114.80 10.149 95.70 9.530 89.90 89.35 9.475 10.667 100.50 11.012 104.00 9,556 90.15 46.506 109.70 40.382 95.20 40,229 94.88 39.082 92.18 39 093 92.20
4,4'-Diaminobenaophenone M. p. Purity
c. .. ..
70
244-6
19.10 12.30 82.00 99.60 99.50 61.50 52.90 99.70
2&4 240-4 243-5 245-6
96.71 97.12 99.30 99.80
244-5 243-5
...
83.20
Net Yield
% of
theory 21.60 14.10 78.60 89.50 88.75 61.90 55.00 89.85 91.25 92.07 92.15 91.53 92.02
and by titration as a primary monoamine gave a purity of 99.8 per cent. From 5 grams of material from run 7 there was isolated 4.15 grams of 4-amino-4'-chlorobenzophenone, which corresponds to 95.4 per cent of the amount calculated (4.35 grams) t o be present. Amination of 4-chloro4'-methylbenzophenone was effected by treating 0.1 mole of the material with 315 grams (5.19 moles) of 28 per cent aqueous ammonia, in the presence of 2.223 grams of cupric oxide (0.028 mole of copper) and 6.00 grams of ammonium nitrate for 30 hours a t 180" C. The yield of 4-amino4'-methylbenzophenone was 91.5 per cent of theory. The ketone melted a t 186" to 187' C. and when titrated as a monoamine showed a purity of 99.7 per cent.
Literature Cited (1) Britton, E. C., and Bryner, Fred, U. S. Patent 1,946,058 (1934). (2) Dietrich, M , , A ~ ~264, . , 174 (1891). (3) Drescher, H. A. E., Fairweather, D. A. W., and Thomas, John, U. S. Patent 1,866,632 (1932).
(4) Groggins, P. H., and Hellbach, R., Chem. 82 M e t . Eng., 37, 693 I_
(IYJU).
(5) Groggins, P. H., Nagel, R. H., and Stirton, A. J., IND. ENG. CHEM.,26, 1317 (1934). (6) hlontagne, P. J., Reo. trav. chim., 21, 25 (1902). (7) Ibid., 25, 384 (1906). (8) Norris, J. F., and Green, E. H., Am. Chem. J . , 26, 496 (1901). (9) Norris, J. F., and Twieg, W. C., Ibid., 30, 395 (1903). RECBXVED May 31,1935. Presented before the Division of Organic Chemistry a t the 89th Meeting of the American Chemical Society, New York, N. Y., April 24 to 26,1935. Contribution No. 249 from the Color and F a r m Waste Division.
