[CONTRIBUTED FROM THE
NOYES CHEMICAL LABORATORY, UNIVERSITY
OF ILLINOIS]
SYNTHESIS OF O-DIAROYLBENZENES AND 1,2-D1AROYLCYCLOHEXANES REYNOLD C. F U S O N , STANLEY B. SPECK, AND WILLIAM R. HATCHARD Received October 6, 1944
It is well known that neither phthalyl chlorides (1)nor o-aroylbenzoyl chlorides (2) can be used in the Friedel-Craft s,ynthesis to produce o-diaroylbenzenes. These compounds yield phthalides. Since phthalide formation, at least with o-aroylbenzoyl ch!orides, would appear t o require cyclization involving an additive reaction of a keto group it seemed probable that this type of reaction could be prevented by the introduction of a mesitoyl group. For example, o-mesitoylbenzoyl chloride (111) would hardly be expected to undergo such a ring closure. This surmise has proved to be correct. Phthalyl chloride has been found to condense v;ith mesitylene in the presence of aluminum chloride to give an 81% yield of a, dimesityl derivative, which has been shown to be o-dimesitoylbenzene (I) rather than the corresponding phthalide (11). Moreover, the same compound was obtained from o-mesitoylbenzoyl chloride (111). The identity of the new diketone was confirmed by its reactions and, in particular, by the discovery that it could be made also by the condensation of mesitylmagnesium bromide with phthalyl chloride and with o-mesitoylbenzoyl chloride. I t had been shown that qm.-phthalyl chloride reacted with phenylmagnesium bromide to produce o-dibenzoylbenzene (3). It is interesting holyever that diphenylcadmium, prepared by the addition of cadmium chloride t o a solution of an equivalent quantity of phenylmagnesium bromide, yielded only 3,3-diphenylphthalide. B similar observation was reported recently by Carter (4).
I
I1
I11
o-Dimesitoylbenzene was unaffected by treatment with strong alkali and failed to undergo cleavage when heated with syrupy phosphoric acid (5). The failure to produce cleavage was probably due to the fact that, even at the boiling point of the phosphoric acid, the diketone did not dissolve. It could be recovered after treatment with Grignard reagents. I n an attempted acylation (6) the dikecone was treated with p-cresyl mesitoate and the binary mixture, Mg-MgIz (7). The only reaction that occurred mas reduction of the diketone. The reduction product has the composition of the corresponding hydroxy ketone (VI). This compound is a vjnylog of mesitoin (V) and may have been formed by ketonization of the enediol (IV) that was t o be expected by analogy with mesitil. This structure was confirmed by the fact 53
56
FUSON, SPECK, AND HATCHARD
that chromic acid oxidation converted the hydroxy ketone (VI) to the parent diketone (I). OH 0 OH 0 OH OH
I
I
I
Mes C=C-C=CMes
I II /==\ \--/
II
Mes CH-CMes
MesCH ClVIes
/ \ \-/ IV
V
VI
When the diketone was heated with zinc dust in the presence of potassium hydroxide it was converted to the corresponding dihydroisobenzofuran, 1 ,3dimesityl-1 ,3-dihydroisobenzofuran (VII) .
1711
VI11
-4n intermediate in this reaction is undoubtedly 1,3-dimesitylisobenzofuran (VIII). However, attempts to isolate this substance were not successful. An attempt was made t o prepare the o-diaroylbenzenes from hexahydrophthalyl chloride. The acid chloride was prepared from trans-hexahydrophthalic acid (8) and accordingly was assigned the trans configuration. Condensation of this acid chloride with benzene, mesitylene, durene, and isodurene was found to yield the corresponding 1,2-diaroylcyclohexanes (IX), but efforts to aromatize these compounds were not successful. That these substances were diketones and not lactones was shown by the fact that they yielded the corresponding tetrahydroisobenzofurans (X), when heated with a mixture of acetic and sulfuric acids. Although no tetrahydroisobenzofurans had been reported previously, the
IX
X
structures seemed certain since the method of preparation was similar t o that used in the synthesis of dihydroisobenzofurans (9, 10). Further evidence of the diketone st.ructure was furnished by an examination of the condensation product with benzene, 1,2-dibenzoylcyclohexane. It was unaffected by treatment with a solution of alcoholic potassium hydroxide. Hydrogenation at 160" under 2000 pounds pressure in the presence of Raney nickel yielded no acidic products. These results exclude the lactone structure. o-Dimesitoylbenzene, when hydrogenated at 175" under 2000 pounds pressure in the presence of a Raney nickel catalyst was converted to the corresponding hydrocarbon, a,a'-dimesityl-o-xylene (XIII) , The structure of the hydrocarbon
DIAROYLBENZENES AND CYCLOHEXANES
57
was established by an independent synthesis. It was produced by the condensstion of 2-chloroisodurene (XI) with a-mesityl-o-tolylmagnesiumbromide (XII).
MesCHz C1 XI
SI1
XI11
Phthalyl chloride was condensed also with durene, isodurene, and 1,3,5triethylbenxene t o produce the corresponding o-diaroylbenzenes. EXPERIMENTAL
The procedure used in the synthesis of the four o-diaroylbenzenes is illustrated b y t h a t employed for o-dimesitoylbenzene. The melting points, recrystallization solvents, and analytical data' for the four diketones are listed in the Table. o-Dimesitoylbenzene. Thirty-four grams of phthalyl chloride was added slowly, with stirring, to a mixture of 86 g. of mesitylene, 50 g. of aluminum chloride, and 110 ml. of carbon disulfide. The mixture was kept in an ice-bath during the addition, stirred at room temperature for twelve hours, and decomposed with cold dilute hydrochloric acid. The solvent and unchanged mesitylene were removed by steam distillation. The diketone, left as a viscous red oil, was treated with 150 ml. of ether. The yellow solid which formed was collected on a filter and washed several times with dilute sodium carbonate solution then with hot ethanol. The o-dimesitoylbenzene was recrystallized from a mixture of highboiling petroleum ether and benzene. It seprirated in nearly colorless crystals. The yield was 50 g., or 81% of the theoretical amount. The diketone was prepared also by the condensation of mesitylmagnesium bromide with phthalyl chloride. Four grams of the acid chloride was added slowly t o a Grignard reagent prepared in ether from 8 g. of bromomesitylerie and 1 g. of magnesium. After the mixture had been heated under reflux for four hours, I t was poured on a mixture of ice and hydrochloric acid. The o-dimesitoylbenzene was recrystallized from benzene; m.p. 230-231"; yield 0.3 g. The melting point of a mixture of this compound with o-dimesitoylbenzene, made by the Friedel-Crafts method, was 230-232". A similar treatment of o-mesitoylbenzoyl chloride with mesitylmagnesium bromide also gave o-dimesitoylbenzene in low yield; m.p. 232"; mixed melting point with a sample made b y the Friedel-Crafts method, 232-233'. Reduction. Asolution of 10 g. of o-dimesitoylbenzene and 7 g. of p-cresyl mesitoate in 15 ml. of n-butyl ether and 35 ml. of toluene was added to the reagent prepared from 1.7 g. of magnesium and 7 g. of iodine in 20 ml. of n-butyl ether. The mixture was stirred forfour hours at 115" in an atmosphere of nitrogen. It developed a deep red color, which changed t o green when air was admitted to the reaction vessel. This color change is characteristic of 1,4-diaroyIbenzenes in the presence of the binary mixture. KO p-cresol was found in the reaction mixture. This indicated that the ester had not reacted in the usual way. About 3 g. of the ester was recovered. I n addition, 8 g. of solid was obtained. After recrystallization from benzene i t melted a t 220-221'. Anal. Calc'd for CzsHraO~:C, 83.83; H, 7.5s. Found: C, 83.77; H, 7.52. Three-tenths gram of the hydroxy ketone was dissolved in 30 ml. of warm glacial acetic acid, and a solution of 1 g . of potassium dichromate in 5 ml. of warm water was added slowly. The reaction mixture rapidly became purple and then green, exhibiting a blue fluorescence. Addition of the oxidizing agent was continued until the solution remained 1 The microanalyses reported in this paper were carried out b y Miss Margaret McCarthy, Miss Theta Spoor, and Miss Dorothy Schneicler.
58
FUSON, SPECK, AND HATCHARD
TABLE I DIAROYLBENZENES, DIAROYLCYCLOHEXANES, AND TETRAHYDROISOBENZOFURAN DERIVATIVES
I comPou ND
Y.P..
".
XECPYSTALLIZATION SOLVENT
MOLECULAR POBMLA
ANALYSIS
Calc'd
i
Found
CssHtsOa /84.29/7.08'84.38/7.28
235-236
Benzene
14.5-235. E
Benzene and petroleum ether
135-136
Ethanol
CisHtoO
@I::,
260-201
n-Amyl dcohol
C*sH:oOp 84.357.5984.647.61
0
188-189
Petroleum ether
Cn8H:sOs
83.12 8.97 83.17 8.92
194-195
Ethanol
C*8H:dO
86.99 8.87 87.23 8.84
270-271
Benzene
CtsH:oOt
84.387.5984.637.87
0
C OMes COMes
C 0-Idur
orCTY
87.10 8.44 87.35 8.48
CO-Idw
-C-Xdur
0::: 0
C ODur 149-149.# Ethanol
CODur
139-140
Petroleum ether
C*aHaeO, 83.12 8.97 82.98 8.79
59
DIAROYLBENZENES A.ND CYCLOHEXANES
TABLE I-Continued
I CLlEPOPND
M.P.,
"c
CCoTepa I 77-78
BECBY STALLIZATION SOIS'ENT
Ethanol
YOLECULAB FOBMULA
1
C,iHaaO,
84.54 8.43 84.79 8.58
ANALYSIS
Calc'd
I
Found
ICOTep
0
COCsHr 113-113. ! Ethanol
CioH~pOt 82.16 6.90 81.91 7.00
COCsHr
97.5
0
Absolute ethanol
2,4,6-Triethylphenyl.
orange and then the solution was heated on the water-bath for fifteen minutes. A curdy precipitate had separated from the acetic acid by this time. The mixture was then poured into 300 ml. of water, becoming successively purple, gray, and yellow. The solid which separated was collected on a filter, washed with ether, andrecrystallizedfrom ethanol. It formed fine white needles melting at 235". The product waa shown by the method of mixed melting points to be o-dimesitoylbenzene (m.p. 235'). The yield waa nearly quantitative. 1 ,9-Dimesityl-l ,9-dihydroisobenzofuran. One gram of o-dimesitoylbenzene waa added t o a boiling solution of 3 g. of potassium hydroxide in 250 ml. of ethanol. After the mixture had been heated for one hour under reflux with no apparent change, 3 g. of powdered zinc, previously activated by contact with hydrochloric acid, was added. The deep orange-red color, which appeared when the zinc was added, faded gradually as the reaction proceeded and disappeared when the heating was continued overnight. The hot solution waa poured into dilute acetic acid and the mixture allowed t o cool. The dihydroisobenzofuran waa extracted with ether and recrystallized from dilute ethanol and from ethyl acetate. The yield was nearly quantitative; m.p. 203-205'. Anal. Calc'd for C*aHraO: C, 87.59; H, 7.91. Found: C, 87.71; H, 8.06. When the reflux period was shortened to three hours the product was found t o be contaminated with I yellow, more soluble material and the mother liquor exhibited the blue fluorescence typical of isobenzofurans. ~ A solution of 7.53 g. of the a , cr'-Dimesityl-o-zylene. ( A ) F T Oo-dimesitoylbenzene. diketone in 150 ml. of methylcyclohexane was treated with hydrogen a t 175" and 2100 lbs. in the presence of two teaspoonfuls of a Raney nickel catalyst. The reaction was stopped when four moles of hydrogen had been absorbed. The product consisted of an oil and asolid. The latter was recrystallized from a mixture of benzene and high-boiling petroleum ether; m.p. 207.5-208.5°; yield 0.8 g. Anal. Calc'd for Cz6H8o: C, 91.17; H, 8.83. Found: C, 91.03; H, 8.80. ( B ) From a-Mesityl-o-bromotoluene. A solution of 2.14 g. of a*-chloroisodurene in dry ether was added t o an ether solution of a Grignard reagent, made from 4 g. of a-mesityl-o-
60
FUSON, SPECK, AND HATCHARD
bromotoluene and 0.34 g. of magnesium. The reaction mixture w a stirred overnight and decomposed in the usual manner. The product was recrystallized from high-boiling petroleum ether; m.p. 206-207". It was shown b y a mixed melting point determination t o be identical with the sample of a ,a'-dimesityl-o-xylene described in the preceding paragraph. a-Mesityl-o-bromotoluene.Thirty-five grams of o-bromobenzyl bromide was added gradually over a two-hour period t o a mixture of 25 g. of mesitylene, 6.64 g. of anhydrous aluminum chloride, and 150 ml. of carbon disulfide. The reaction mixture was stirred during the addition and for twelve hours afterward. The product, isolated in the usual manner, It crystallized from ethanol was found t o boil at 164-168' (4 mm.) and to melt a t 69.5-70.5'. as small white needles. Anal. Calc'd for ClsHlrBr: C, 66.44; H, 5.92. Found: C, 66.54; H, 6.12. 3,s-Diphenytphthalide from phthalyl chloride and diphenylcadmium. To a cold Grignard solution containing approximately 0.175 mole of phenylmagnesium bromide was added 17.4 g. of anhydrous cadmium chloride. After the solution had been stirred for thirty minutes it gave a negative test for the Grignard reagent (11, 12). A solution of 14.2 g. of sym.phthalyl chloride was added, slowly and with stirring. After the solution had been heated under reflux for one hour,it was decomposed in the usual manner. The3,3-diphenylphthalide, after recrystallization from ethanol, melted at 112-113' and did not depress the melting point of a n authentic sample. The yield was 32%. The remainder of the product was a heavy viscous oil which did not crystallize. Hydrogenation of 3,3-diphenylphthalide. The hydrogenation was carried out i n a Parr bomb with a Raney nickel catalyst a t a pressure of 2000 lbs. and a temperature of 175". A solution of 5.32 g. of the phthalide in benzene absorbed four moles of hydrogen. The product was o-benzohydrylbenzoic acid. It was isolated in the usual way and recrystallized from a mixture of benzene and high-boiling petroleum ether; yield4.1 g.;m.p. 160-161O. The melting point reported by Drory (13) was 162". A mixed melting point with a specimen prepared by the method of Baeyer (1) showed no lowering. 1,i-Dimesitoylcyclohexane. Ethyl phthalate (600 g.) was hydrogenated at 175" and 2000 lbs. pressure in the presence of a Raney nickel catalyst. The product (537 g.), presumably a mixture of cis- and trans-ethyl hexahydrophthalates, boiled a t 150" (23 mm.). One hundred grams of this liquid was dissolved in 500 ml. of a 10 solution of ethanolic potassium hydroxide t o which a small piece of metallic sodium had also been added. After the mixture had been boiled under reflux for two hours, water was added slowly while alcohol was removed by distillation. The aqueous solution was boiled until saponification was complete and acidified with hydrochloric acid. The precipitated acid weighed 71 g. and melted It was assumed to be trans-hexahydrophthalic acid. at 210-218'. The hexahydrophthalyl chloride was made by the use of phosphorus pentachloride. A mixture of 30 g. of the acid and 74 g. of phosphorus pentachloride was heated for twelve hours. The acid chloride, isolated in the usual way, boiled at 110' (6 mm.) and weighed 28.7 g. The use of a mixture of thionyl chloride and zinc chloride gave a somewhat lower yield. A solution of 3.9 g. of the acid chloride in 25 ml. of carbon disulfide was added over a period of one hour t o a mixture of 16 g. of mesitylene, 6 g. of anhydrous aluminum chloride, and 60 ml. of carbon disulfide. The reaction mixture was stirred overnight, decomposed, and washed in the usual manner. After the carbon disulfide and excess mesitylene had been removed by steam distillation, the resinous residue was washed with ether. The crystalline product which formed was recrystallized from a mixture of benzene and high-boiling petroleum ether; yield 2.5 g. Similar results were obtained when benzene, durene, and isodurene were condensed with trans-hexahydrophthalyl chloride. The melting points, recrystallization solvents, and analytical data for the four 1,2-diaroylcyclohexanes are listed in the Table. A solution of 6 g. of trans-1,a-dimesi1,3-Dimesityl-4,6,6,7-tetrahydroisobenzofuran. tolycyclohexane, 100 ml. of glacial acetic acid, and 50 ml. of 60% (by volume) sulfuric acid
DIAROYLBENZENES AND CYCLOHEXANES
61
was warmed and stirred for eight hours and poured into 200 ml. of water. The isobenzofuran was recrystallized from ethanol; yield 5.1 g. The diketones obtained by condensation of trans-hexahydrophthalyl chloride with benzene, durene, and isodurene were converted t o the corresponding 1,3-diaryl-4,5,6,7tetrahydroisobenzofurans in a similar manner. The melting points and other data relative t o these four tetrahydroisobenzofurans are listed in the Table. SUM.MARY
Phthalyl chloride has been condensed with mesitylene, durene, isodurene, and 1 , 3 ,Btriethylbenzene in the presence of aluminum chloride to yield the corresponding o-diaroylbenzenes. The structure of o-dimesitoylbenzene has been confirmed by a study of its reactions and by an independent synthesis. The new synthesis of diketones has been extended to trans-hexahydrophthalyl chloride, which was found to condense with benzene, mesitylene, durene, and isodurene to yield the corresponding 1,2-diaroylcyclohexanes. These compounds were converted by dehydration to the corresponding 1,3-diaryl-4 ,5,6,7tetrahydroisobenzofurans, a type of compound not previously known. URBANA, ILL. REFERENCES (1) BAEYER,Ann., 202, 50 (1880). (2) MEYER,Monutsh., 22,788 (1901); 28, 1231 (1907). Ber., 62B, 940 (1929). (3) CLAR,JOHN,AND HAWRAN, (4) CARTER, I O W U StUte COll. J. SCi., 16,63 (1940). (5) KLAGESAND LICKROTH, Ber., 32, 1549 (1899). (6) FUSON,BOTTORFF, FOSTER, AND SPECK, J. Am. Chem. Soc., 64, 2573 (1942). (7) GOMBERG AND BACHMANN, J. Am. Chem. Soc., 49,236 (1927). (8) PRICEAND SCHWARCZ, J. Am. Chem. Xoc., 62, 2893 (1940). AND GOLD,J. Am. Chem. Soc., 62,56 (1940). (9) ADAMS (10) ADAMSAND WEARN,J. Am. Chcm. SOC.,62, 1233 (1940). (11) GILMAN AND SCHULZE, J. Am. Chem. Soc., 47,2002 (1925). AND HECK,J . Am. Chem. SOC., 62,4949 (1930). (12) GILMAN (13) DBORY,Ber., 24,2573 (1891).
