[CONTRIBUTION FROM
THE
NOYESCHEMICAL LABORATORY, UNIVERSITY OF ILLINOIS]
GRIGNARD REACTIONS INVOLVING THE BENZENE NUCLEUS RElYNOLD C. FUSON, M. D . ARMSTRONG,
AND
S.
B. SPECK
Received February 2, IO@
The Grignard reagent recently has been found to add in the 1,4 manner to the a,p-unsaturated ketone systems in a- and p-mesitoylfurans (1). These con-
densations are remarkable in that they involve a double bond of the furan nucleus. Reactions are known which involve a benzene ring. Phenylmagnesium bromide condenses in this manner with benzophenone ani1 (I) (2), a ,p-diphenylbenzalacetophenone (11) (3), benzanthrone (111) (4), and naphthacenequinone.
I
I1
I11
It has now been found possible to accomplish this type of reaction with mesityl aryl ketones. Benzoylmesitylene (IV) has been treated with phenylmagnesium bromide and it has been established that condensation occurs in the 1 , 4 manner and involv'esa double bond of a benzenoid ring. The product obtained in largest amount was 2-phenylbenzoylmesitylene (V).
VI The structure of this compound was established by degradation and synthesis. Cleavage with syrupy phosphoric acid produced o-phenylbenzoic acid. The 297
298
FUSON, ARMSTRONC, AND SPECK
phenylated ketone (V) was synthesized from 2-xenylmagnesium iodide and mesitoyl chloride.
It (V) is presumably an oxidation product of the enol (VI) that would be expected. Although the enol could not be isolated, evidence of its formation was gained from work with other ketones. a-Mesitoylnaphthalene (VII),l for example, condensed with phenylmagnesium bromide to yield an oil from which mesitoic acid and 2-phenyl-l-naphthol could be obtained by exposure to air. These are the cleavage products to be expected for the enol (VIII).
VI11
VI1
MesC O2H
p-Tolyl mesityl ketone and p-tolylmagnesium bromide give rise to a compound that by analogy was identified as 2-mesitoyl-4' 5-dimethylbiphenyl (IX). ~
MesC OnCH3 \\-/ I CeH4 CH3 I
Ix
Phenyl- and a-naphthyl-magnesium bromides condensed with p-bromobenzoylmesitylene to yield highly unsaturated products ; the structure of these compounds was not established. EXPERIMENTAL
Benzoylmesitylene and phenylmagnesium bromide. A solution of 50 g. of benzoylmesitylene in 150 cc. of dry ether was added slowly to a refluxing solution of phenylmagnesium bromide, prepared from 132 g. of bromobenzene and 21 g. of magnesium in 500 cc. of dry ether. After addition was completed the solution was stirred and refluxed for an additional five hours. The reaction mixture was then cooled and decomposed with dilute hydrochloric acid. The ether layer was washed with water and dried over calcium chloride. The ether was removed by evaporation. The resulting oil was distilled i n zlucuo. Biphenyl and benzoylmesitylene were found in the fore fraction. The fraction boiling a t 200-205" (4 mm.) was dissolved in methyl alcohol and a white compound was induced to crystallize. After two recrystallizations from ethanol, the 2phenylbenzoylmesitylene melted at 89-90'; yield 8 g. or 18% of the theoretical. Anal.2 Calc'd for C2PH200:C, 88.00;H, 6.67. Found: C , 87.59; H, 6.73. 1 2
Mes is used to represent the mesityl radical. Microanalyses by Miss Mary S. Kreger and Mr. L. G. Fauble.
GRIGNARD REACTIONS WITH T H E BENZENE NUCLEUS
299
One gram of 2-phenylbenzoylmesitylene was heated with 15 cc. of syrupy phosphoric acid for four hours. The mixture was poured into water, extracted with ether, and the ether layer extracted with 10% sodium carbonate solution. Acidification of this extract gave a small amount of a white material which when crystallized from ethanol melted a t 112-113". A. mixed melting point with o-phenylbenzoic acid, m.p. 113", showed no depression. In addition to biphenyl, benzoylmesitylene, and 2-phenylbenzoylmesitylene, the original mixture contained a small amount of a very viscous liquid, b.p. 210-250" (4 mm.) from which was obtained a white crystalline compound, melting at 245-246'.
A n a l . Calc'd for C22H2102:C, 83.02; H, 6.91. Found: C,83.43; H, 6.55. An acetate of this compound was prepared by heating a small amount with acetic anhydride for one hour. The product was purified by recrystallization from methanol. It melted a t 101" (cor.). A n a l . Calc'd for CZ4HZC03: C,80.00; H, 6.66. Found: ,:C 79.98; H, 6.20. The compound, CZ2Hz2O2, and its acetate were not further investigated. The distillation of the original reaction mixture left a large amount of tarry residue. Synthesis of 2-phenylbenzoylmesitylene. 2-Iodobiphenyl was prepared according t o the directions of Gilman, Kirby, and Kinney (2). One hundred and seventy grams of 2-aminobiphenyl yielded 195 g. (70%) of 2-iodobiphenyl; b.p. 169-170" (17 mm.). 2-Biphenylmagnesium iodide was prepared from 40 g. of 2-iodobiphenyl and 5 g. of magnesium in 120 cc. of dry ether; this solution was filtered into another flask. A solution of 24 g. of mesitoyl chloride (5) in 100 cc. of dry ether was added slowly to the clear solution of the reagent a t such a rate that the ether refluxed gently. The reaction mixture was then refluxed and stirred for three hours, cooled, decomposed with ice and dilute hydrochloric acid, and worked up in the usual manner. After one recrystallization from ethanol, 32 g. (80% yield) of product was obtained; melting point and mixed melting point 89-90". Oxidation of enol intermediate obtained b y the addition of phenylmagnesium bromide to benzoylmesitylene. T o a solution of phenylmagnesium bromide prepared from 8.8 g. of bromobenzene and 1.35 g. of magnesium in 50 cc. of dry ether, was added slowly a solution of 10 g. of benzoylmesitylene in 30 cc. of ether. The remainder of the reaction was carried out in the usual manner. The reaction mixture was cooled in an ice-salt-bath and carefully decomposed with ice and hydrochloric acid. The ether layer was washed with ice-wltter and quickly transferred to a round-bottomed flask immersed in an ice-bath. A stream of dry air was passed through the solution for several hours, a little low-boiling petroleum ether being added from time t o time t o replace the solvent lost by evaporation. The ether was removed and its resulting dark brown oil was dissolved in absolute ethanol, which was allowed to evaporate slowly. A small amount of crystalline material separated and was isolated by dissolving the oil in a mixture of low-boiling petroleum ether and benzene and filtering the suspension. After two crystallizations from benzene the compound melted at 245" and gave no depression of melting point when mixed with the compound C22H1202 obtained previously; yield, 2.0 g. The remaining oil was distilled, and from the distillate was obtained 3 g. (22% yield) of 0-phenylbenzoylmesitylene, m.p. 84-88'. a-Naphthoylmesitylene and phenylmagnesium bromide. A solution of 5 g. of oc-naphthoylmesitylene In 50 cc. of benzene was added to the Grignard reagent prepared from 10.5 g. of bromobenzene and 1.6 g. of magnesium in 50 cc. of dry ether. Benzene was added t o the reaction mixture and ether was allowed to evaporate until the temperature of the vapors reached 55" The reaction mixture was refluxed and stirred for seventy-five hours. At the end of this time i t was R light orange color. The solution was decomposed and worked up in the usual manner. The product was a black, sticky tar. The tar was dissolved in a
300
FUSON, ARMSTRONG, AND SPECK
small amount of benzene, and the solution allowed to stand in an ice-box for several months. A white compound separated and was recrystallized from benzene; yield, 1g., m.p. 210-211".
Anal. Calc'd for ClaHI20:C, 87.27; H, 5.45. Found: C, 88.14; H, 5.11. This compound was evidently 2-phenyl-1-naphthol; i t underwent oxidation by atmospheric oxygen and other mild oxidizing agents to yield a brilliant red compound. Examination of the literature showed that 2-phenyl-1-naphthol had been prepared, though never purified, and was found to be easily oxidized to give a binaphthone, which melted at about 220'. The oil from which the abbve compound was obtained was dissolved in ether and extracted with 10% sodium bicarbonate solution. Acidification of this solution gave 0.4 g. of mesitoic acid. The ether solution was now extracted with 10% sodium hydroxide solution. This solution was nearly neutralized with acid and a dilute solution of potassium ferricyanide added. A voluminous deep purple precipitate formed, was extracted with benzene, and recrystallized from a benzene-ligroin mixture. A small amount of an almost black compound was obtained. It melted above 200" and was probably a binaphthone. Preparation of p-bromobenzoylmesitylene. A solution of 160 g. of p-bromobenzoyl chloride in 500 cc. of carbon disulfide was added slowly to a well-stirred mixture of 106 g. of anhydrous aluminum chloride, 90 g. (105 cc.) of mesitylene, and 350 cc. of carbon disulfide. The addition was made over a period of two hours, and the reaction mixture was stirred a t room temperature for five hours after the addition was completed. Most of the solvent was then distilled, and the pasty mass that remained was decomposed by pouring i t into a mixture of ice and concentrated hydrochloric acid. The mixture was transferred to a separatory funnel, and the crude product was extracted with ether. The ether layer was washed with water, 10% sodium hydroxide solution, and again with water. The solvent was then evaporated and the crude product was recrystallized twice from 95% ethanol. Yield, 170 g. (75%); m.p. 72-73" (cor.).
Anal. Calc'd for C18H16BrO:C, 63.37; H, 4.95. Found: C, 63.36; H, 4.39. p-Bromobenzoylmesitylene and phenylmagnesium bromide. The reagent was prepared from 20 g. of bromobenzene and 4 g. of magnesium in 100 cc. of dry ether. This solution was filtered through glass wool and was added slowly to a solution of 30 g. of p-bromobenzoylmesitylene in 200 cc. of dry ether. The reaction mixture was refluxed gently and was well stirred during the addition, which was carried out over a period of two hours. The intense red solution which was obtained was refluxed and stirred for an additional five hours and decomposed with dilute acid. Removal of the solvent left an oily semi-solid product, which was washed with methanol. The yellow solid was crystallized once from methanol and melted a t 119-120"; yield, 17 g. (43%). The pure compound melted at 121" (cor.).
Anal. Calc'd for C22H2;BrO:C, 69.29; H, 5.51. Found: C , 69.40; H, 5.69. From the mother liquor was isolated a yellow solid which, when crystallized from methanol, melted at 131" (cor.).
Anal. Calc'd for Cz,HzlBrOz: C, 66.75; H, 5.28. Found: C, 67.49; H, 5.27. Properties of the compound C21H21Br0, m.p. 191". This compound gives no precipitate with alcoholic silver nitrate. Treatment of the bromo compound with a 10% solution of sodium methoxide in methanol, produced a deep green solution.
GRIGNARD REACTIONS WITH THE BENZENE NUCLEUS
301
Bromination. One gram of the compound was dissolved in 20 cc. of glacial acetic acid and 2.5 cc. of bromine added slowly to the solution. The reaction mixture became slightly warm and a small amount of hydrobromic acid fumes was noticed. The flask was allowed to stand a t room temperature for thirty minutes. At the end of this time a white crystalline solid had separated; i t was collected on a filter, washed with glacial acetic acid, and dried; yield, 1.25 g. After several recrystallizations from absolute ethanol i t melted a t 175' (cor.). Anal. Calc'd for C2zHlsBrSO:C, 37.71; H, 2.71. Found: C,37.47;H, 2.79.
The compound CzaHzlBrOcould not be acetylated or reduced and all attempts at dehydrogenation failed. It did not undergo a Diels-Alder condensation with maleic anhydride. A Zerewitinoff determination indicated that there was no active hydrogen. p-Bromo benzoylmesitylene and a-naphthylmagnesium bromide. a-Naphthylmagnesium bromide was prepared from 18 g. of a-naphthyl bromide and 4 g. of magnesium in a mixture of 100 cc. of dry ether and 20 cc. of dry benzene. The reagent was filtered through glass wool and slowly added t o a solution of 10 g. of p-bromobenzoylmesitylene in 50 cc. of dry ether. The reaction mixture was stirred and refluxed overnight and decomposed in the usual manner. After removal of the solvent, the oily residue was subjected to steam distillation until a clear distillate was obtained. The residual dark colored oil hardened t o an amorphous solid, which was difficult to crystallize. A small amount of the product was obtained crystalline by dissolving the oil in chloroform, adding low-boiling petroleum ether t o the solution until it almost became turbid, and allowing the solvent to evaporate slowly. The solid was collected on a filter and washed with absolute ethanol. After several recrystallizations from ethanol i t was obtained as colorless crystals melting at 195" (cor.). Anal.
Calc'd for Cz6Hz3BrO:C, 72.39; H, 5.34. Found: C, 72.74;H, 5.40.
The filtrate was set aside and allowed to evaporate. After several weeks, part of the oil began to crystallize. The crystals were separated and the oil was taken up in alcohol and allowed to evaporate again. Eventually most of the oil crystallized. The compound was purified by recrystallization from absolute ethanol. It melted at 143' (cor.) and was the main product of the reaction. Anal. Calc'd for CleHzaBrO: C, 72.39;H, 5.34. Found: C, 72.66;H, 5.42. These two compounds are isomeric and have the composition of an addition product between p- bromobenzoylmesitylene and naphthalene. p-Toluylmesitylene and p-tolylmagnesium bromide. A solution of 20 g. of p-toluylmesitylene in 50 cc. of dry ether was added slowly to a solution of p-tolylmagnesium bromide made from 2.8 g. of magnesium and 17.1 g. of p-bromotoluene in 60 cc. of dry ether. The mixture was refluxed for four hours and decomposed in the usual manner. The thick yellow oil obtained was distilled i n vacuo. The first fraction of 8.5 g. consisted of unchanged p-toluylmesitylene. A second fraction of 5.1 g. was an oil that failed t o crystallize. From the final fraction was obtained yellow crystals melting a t 101" (cor.). These had the composition of 2-mesitoyl-4',5-dimethylbiphenyl. Anal.
Calc'd for C24H2*0:C, 87.75;H, 7.37. Found: C,87.78;H, 7.48. SUMMARY
It has been shown that benzoylmesitylene condenses with phenylmagnesium bromide in the 1 , 4 manner to the conjugated system formed by the carbonyl group and a double bond of the benzene ring.
302
FUSON, ARMSTRONG, AND SPECK
Similar results have been obtained with p-bromobenzoylmesitylene, amesitoylnaphthalene, and p-toluylmesitylene. URBANA, ILL. REFERENCES (1) LUTZAND REVELEY, J. Am. Chem. Soc., 63, 3178 (1941); FUSON,KAISER,AND SPECK, J . Org. Chem., 6, 845 (1941). (2) GILMAN, KIRBY,AND KINNEY,J . Am. Chem. Soc., 61, 2252 (1929). AND NYGAARD, J . Am. Chem. SOC.,62,4128 (1930). (3) KOHLER J . Am. Chem. SOC.,67, 740, 1322 (1935); ALLENAND GILMAN, (4) ALLENAND OVERBAUGH, J . Am. Chem. SOC.,68, 937 (1936). (5) FUSON, CORSE,AND MCKEEVER, J . Am. Chem. SOC.,61,2010 (1939).
