[CONTRIBUTION FROM
THE
NOYESCHEMICAL LABORATORY, UNIVERSITY OF ILLINOIS]
A SYNTHESIS OF FULVENES REYNOLD C. FUSON, CHARLES L. FLEMING, PETER F. WARFIELD, DONALD E. WOLF
AND
Received October 16, 1944
In connection with attempts to use trans-l,2-dibenzoylethylene(I) in the Michael condensation, it was noticed that sodium ethoxide caused the unsaturated diketone t o condense with itself to produce a yellow solid, melting a t 164-1135'. The properties of this compound indicated that it was a fulvene derivatibe. When the investigation was a t this stage (1938) Gardner and Rydon (1) reported a compound, made by the same method and having the melting point 161°, which appeared to be identical with ours. For their compound these investigators postulated the structure 1,4,5-tribenzoyl-2-phenylcyclopentadiene (or a tautomer of this compound). Our work confirms their structure except that the enolic form is indicated. Subsequent work has revealed that other 1,2-diaroylethylenes behave in the same manner. The reaction is brought about by treating the diketones with an equimolecular amount of sodium ethoxide. Other diketones studied were trans-di(p-toluy1)ethylene (11) and cis- and trans-di-(p-chlorobenzoy1)ethylene (111). Even more remarkable was the discovery that diaroylethanes would yield the same products as the corresponding ethylenes.
It should be mentioned, however, that the yields were never high and that the corresponding benzoic acids were always produced together with large quantities of tars. The ethanes reacted much less readily than the ethylenes and afforded lower yields of crystalline products. The condensation did not occur when trans-dimesitoylethylene was used. The only crystalline compound that could be isolated was an oxidation product, which might be a mixture of the enolic forms of lJ4-dimesity1-l,2,4-butanetrione (2). A study of the yellow solids showed that they resembled one another closely. The evidence that was accumulated indicated that these compounds were f u l 121
122
FUSON, FLEMING, WARFIELD, AND WOLF
vene derivatives. On this assumption the derivative of dibenzoylethylene, for example, was formulated as 1,4-dibenzoyl-2,6-diphenyl-6-hydroxyfulvene(IV). CeH6COH
II
C
/ \
CeH6COC
II
HC-
c c0 csH5 I CCs&
IV This compound melted at 164-165" and had a molecular formula (C32HzzOa) which corresponded to two molecules of dibenzoylethylene minus the elements of water. The chloro compound had a similar composition. Titration of the latter in ethanol showed it to be a monobasic acid. I n this respect and in color it is similar to the dibenzofulvene derivative described by Kuhn and Levy (3). They found that the fluoreneoxalic ester of Wislicenus (4) was in reality an enol (V) which could be titrated.
II
HOCCOZR V The new fulvenes are stable to alkaline reagents but are decomposed by acids. They differ from the fulvenes of Thiele ( 5 ) in being resistant to attack by atmospheric oxygen and bromine. This is doubtless on account of the higher degree of conjugation found in the dibenzoyldiphenylfulvenes. The following mechanism accounts satisfactorily for the format,ion of the fulvenes from the diaroylethylenes. The first step (a) is the dimerization of the ethylene, a reaction similar to that observed by Gilbert and Donleavy for acrolein (6) and a-methylacrolein (7). Cyclodehydration (b) and isomerization (c) then occur.
2ArCOCH=CHCOAr
ArCOCHCHz COAr
ArCOCH-CCOAr
A r c OC=CHC OAr
ArCOC=CH
(a) --+
None of these steps involves any unusual assumption. The formation of the fulvenes from the diaroylethanes is more difficult t o explain. It is possible to write a sequence of transformations by which a diaroylethane could yield a cyclopentane instead of the observed cyclopentadiene derivative. This is shown by the following outline:
123
SYNTHESIS O F FULVENES
ArCCH2CH2COAr
Arc10 iCH2 CH2 COAr j
I
Ar CO C!H.i$2H2 , ........ COAr
---+ (4
II
ArCOCCH2 COAr
(4 -+ ArCO
I
CH
/ \ CHCOAr I I
ArCHCH2CH2COAr (f) ArCOCH
I
/.
A r c 0 C=CHCOAr VI
-+
CH2-CHAr VI1
The first step (d) is an aldol condensation followed by loss of water. In the presence of sodium ethoxide the product would be expected t o isomerize (e) to the more highly conjugated molecule (VI). The latter would normally undergo an internal Michael condensation (f) in the presence of sodium ethoxide. The final stage in the formation of the fulvene would, on this basis, consist of dehydrogenation. It is also possible that dehydrogenation occurs as the first step resulting in the conversion of the ethane t o the ethylene. However, dehydrogenation of the cyclopentane seems more probable and evidence, presently t o be given, shows it to be possible.' A plausible explanation of the dehydrogenation emerges from the observation of :Lutz and Kibler (9) that the bromomagnesium dienolates of diaroylethanes are oxidized to the corresponding ethylenes by hydrolysis in the presence of an oxidizing agent. Since the fulvenes were formed in reaction mixtures exposed to the air, such an oxidation may be responsible for the transformation of the cyclopentanes to the fulvenes. The two requisite dehydrogenations (g and i) could take place normally, provided that each is followed by an isomerization (h and j). The rearrangements are to be regarded as normal since each enhances the acidic nature of the molecule. ArCO ArCO
1
I
CH
C
/ \
ArCOCH
I
/ \ CCOAr (h) I I -+
CHCOAr (g) ArCOCH
I
CH2-CHAr
-+
C Hz-CHAr
VI1
VI11
ArCO
I
CH
/ \
ArCOC
ArCO
I
C
/ \
-
CHCOAr (i) ArCOC CCOAr (j) -+ IV II I II 1 HC-CHAr HC-CHAr IX
1 This postulated dehydrogenation recalls the conversion of ethyl l-chlorohexahydro-otoluate t o o-toluic acid by treatment with ethanolic potassium hydroxide (8).
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FUSON, FLEMING, WARFIELD, AND WOLF
Arc0
I
CH
/ \ CCOAr 1 I/
ArCOCH
Hz C - C h X
Fortunately, this hypothesis could be put to test. In the phenyl series, VI11 and IX differ from the cyclopentene derivative (X) of Lutz and Palmer (10) only in the position of the double bond. All three of these isomers would certainly react in the same manner to yield the corresponding fulvene. The cyclopentene derivative of Lutz and Palmer was synthesized and treated in the usual manner with sodium ethoxide. The product was the expected fulvene. The same result was obtained by use of the parent cyclopentanol. This synthesis serves t o confirm not only the structures assigned to the new fulvenes but also the mechanisms postulated for their formation. Consideration was given to the possibility that the dehydrogenation (g-i) might be general for 1,2-diaroylcyclopentanes. 1,2-Dimesitoylcyclopentane (XI) was made and subjected to the sodium ethoxide treatment. The product was a neutral, colored compound having the composition of a dimesitoylcyclopentadiene. The structure indicated by XI1 seems probable. MesC 0CH-CH2
MesCOC-CH
MesCOCH-CH XI
/CH MesC 0 C-CH2 XI1
\
(1
\\
EXPERIMENTAL
All melting points are corrected. Condensation of trans-1,R-dibenzoylethylene. Ten grams of dibenzoylethylene, prepared by the method of Conant and Lutz (II), was dissolved i n 500 ml. of dry benzene. To this solution was added a t room temperature a solution of 1.1 g. of sodium i n 25 ml. of absolute ethanol. The solution immediately developed a deep red color. After being allowed t o stand for nine hours, the solution was acidified with acetic acid and washed with water, with a saturated sodium bicarbonate solution, and again with water. Evaporation of the benzene left the product as a heavy, red oil. It crystallized when methanol was added. The 1,4-dibenzoyl-Z,6-diphenyl-6-hydroxyfulvene(IV) was collected on a filter and purified by recrystallization from acetone. It formed yellow needles melting a t 164-165'; yield 31%. Anal. Calc'd for CazHzaOa: C, 84.56; H, 4.88; mol. wt. 454. Found: C, 84.89; H, 4.53; mol. wt. (ebullioscopic i n benzene), 473. The sodium bicarbonate solution used t o wash the benzene solution was found t o contain 0.6 g. of benzoic acid. The same fulvene was formed from 1,2-dibeneoylethane by the above procedure. However, the reaction mixture was heated overnight under reflux and even then contained unchanged dibenzoylethane.
SYNTHESIS OF FULVENES
125
The new fulvene was sparingly soluble i n ethanol and i n ether, moderately soluble i n ethyl acetate, and readily soluble i n acetone and i n benzene. It was insoluble i n cold dilute hydrochloric acid or sodium hydroxide solution b u t dissolved readily i n a hot 10% solution of sodium bicarbonate or a hot solution of sodium hydroxide. It was recovered unchanged after being heated under reflux for fifteen hours with a mixture of water, ethanol, and pot:tssium hydroxide. With concentrated sulfuric acid i t gave a deep red solution. An acet,one solution of the fulvene decolorized a potassium permanganate solution immediately. It decolorized a cold solution of bromine i n carbon tetrachloride with the evolution of hydrogen bromide. It gave no color with ferric chloride and did not reduce an ammoniacal solution of silver nitrate. It was not reduced by sodium hydrosulfite. Condensation of trans-di- (p-toluy1)ethylene (11 ) . The 1,4-di- (p-toluyl)-2,6-di- (p-to1yl) 6-hydroxyfulvene crystallized from acetone in yellow needles; m.p. 172-172.5'. Anal. Calc'd for C36H3003: C, 84.68; H, 5.92. Found: C, 84.92; H, 5.97. 1)i-(p-toluyl)ethane,when heated under reflux for fifteen hours i n the presence of a n equimolecular amount of sodium ethoxide, gave the same fulvene as did the corresponding ethylene . Roth the ditoluylethylene and the ditoluylethane yielded p-toluic acid also. Condensation of the di-(p-chZorobenzoyZ)ethyZenes. Both the cis- (12) and the trans-di(p-chlorobenzoy1)ethylenes ( l l ) , when treated with molar amounts of sodium ethoxide, according t o the above directions, yielded p-chlorobenzoic acid and 1,.l-di-(p-chlorobenzoyl)-2,6-di-(p-chlorophenyl)-6-hydroxyfulvene.The latter crystallized from a mixture of acetone and ethanol i n orange needles; m.p. 219-219.5'. Anal. Calc'd for C32H~&1403: C, 64.90; H, 3.04; neut. equiv., 592. Found: C , 64.70; H, 3.25; neut. equiv., 595. The same fulvene, as well as p-chlorobenzoic acid, was formed from di-(p-chlorobenzoy1)ethane by the above procedure. The reaction mixture was alloned t o stand for forty-eight hours a t room temperature. The chlorofulvene was recovered unchanged after nine hours of heating under reflux with dilute alcoholic potassium hydroxide solution. Prolonged heating with a concentrated solution of potassium hydroxide was likewise without effect. Condensation of trans-dimesitoylethylene. The oily product obtained when trans-dimesitoylethylene (11) was treated with sodium ethoxide, was very difficult t o purify. It was dissolved i n methanol and the solution allowed t o stand. After several weeks yellow rhombic crystals formed. When recyrstallized from ethanol they separated as yellow plates; m.p. 111.5-112". Anal. Calc'd for C22H2403: C, 78.54; H, 7.19. Found: C, 78.38; H, 7.19. Formation of a fulvene from I-phenyl-%,J,~-tribenzoyl-l-cyc20pentanol.The cyclopentano1 was prepared according to the directions of Lutz, Love, and Palmer (13). One gram of the cyclopentanol was dissolved i n dry benzene and t o the solution was added a solution of 0.05 g. of sodium i n absolute ethanol. The mixture was allowed to stand fifteen hours a t room temperature. A t a n precipitate formed. The mixture was acidified with acetic acid, washed with water and with a sodium bicarbonate solution. Evaporation of the benzene left a red oil which crystallized when methanol was added. The product was purified by recrystallization from acetone. It formed yellow needles melting a t 164-165". The method of riixed melting points showed i t t o be the dibenxoyldiphenylfulvene (IV). I n addition t o the yellow crystals, small amounts were obtained of two colorless products. One of these formed rhombic crystals melting a t 169-170" and may be the same as Lutz and Palmer's bis-dibenzoylethane-B (10). The other formed white plates melting at 119120" These compounds were not investigated further. Formation of a fulvene from I-phenyl-%,J,.+-tribenzoyl-I-cyclopentene. Five grams of t h e cyclopentene, prepared by the procedure of Lutz and Palmer (lo), was treated with sodium ethoxide in the manner described for the cyclopentanol except t h a t the time of
126
FUSON, FLEMING, WARFIELD, AND WOLF
reaction was twenty-four hours. Yellow crystals were obtained which proved to be the fulvene (IV). A small amount of an unidentified acid was also isolated. trans-1 ,d-Cyclopentanedzcar60rylze aczd. The method of preparation was that of Fuson andCole (14) modified i n certain respects. The formation of the ethyl a,a'-dibromopimelate took place in yields of from 7576 to 85%. The addition of a trace of red phosphorus increased the yields only very slightly. I t was observed that i t is very necessary t o stir the reaction mixture or t o have some means of shaking the flask when the ethanol is added t o the cold solution of the dibromo acid chloride; otherwise the reaction may easily get out of control. The yields of the ester were improved by complete removal of the excess thionyl chloride from the pimelyl chloride. This can be effectcd by adding asmall portion of chloroform after the bulk of the thionyl chloride has been distilled and then removing the chloroform along with the last traces of thionyl chloride by distillation under diminished pressure from a water-bath at not higher than 60". The yields i n the ring-closure were excellent,usually being nearly 90%. The next step, however, had to be modified since the conversion of the mixture of cis and trans isomers t o the trans isomer by a sealed-tube reaction did not lend itself to large-scale synthesis. It was found that, by allowing the hydrolysis to proceed for from four t o five days, tlietrans acid could be isolated i n a very pure state and i n yields of about 95%. Twenty-eight grams of ethyl 1-cyano-1.2-cyclopentanedicarboxylateand 100 ml. of concentrated hydrochloric acid (38Oj,) were heated under reflux i n a flask with a ground-glass joint for ninety hours. The solid which separated on cooling was treated with X'orit and recrystallized from water; yield 17 g. (92%) of pure trans-l,2-cyclopentanedicarboxylic acid, m.p. 160-161". trans-1 ,d-Dimesitoylcyclopentane. Thirty-five milliliters of thionyl chloride was added slowly to 6 g. of trans-l,2-cyclopentanedicarboxylicacid. A vigorous reaction took place. When all of the thionyl chloride had been added, the mixture was allowed t o stand overnight a t room temperature, then heated a t 60" for one hour. Most of the thionyl chloride was removed by the water-pump, and 20 ml. of chloroform was added. It was immediately removed by the water-pump and gentle heating on a steam-bath. This method aided i n the complete removal of the thionyl chloride by raising the temperature of the distillation. The acid chloride was distilled i n vacuo giving 8.5 g. (94%) of colorless liquid, b.p. 120-125° (22 mm.), 97" (6 mm.). Twenty-five grams of aluminum chloride was added very slowly with vigorous stirring t o a mixture of 30 ml. of mesitylene, 20 g. of the acid chloride, and 200 ml. of carbon disulfide. The reaction was allowed t o proceed a t room temperature until fumes of hydrochloric acid were no longer evolved (three hours). The mixture was decomposed by pouring i t into a mixture of ice and hydrochloric acid, the carbon disulfide layer separated, and the water layer extracted with two 20-ml. portions of carbon disulfide. The extracts were added t o the separated carbon disulfide layer and this was then washed with 5% sodium hydroxide and water. An equal volume of water was added and the mixture was steam-distilled t o remove the carbon disulfide and excess mesitylene. The residual water solution was extracted with four 50-ml. portions of ether, the extracts were combined, dried with calcium chloride for ten minutes, and then with Drierite overnight. The ether was removed by distillation from a steam-cone and the remaining oil was treated with Norit and recrystallized from ethanol. Two recrystallizations gave 20.6 g. (51% of pure trans-l,2-dimesitoylcyclopentane, m.p. 92-93'. AnaE. Calc'd for C25H3002: C, 82.83; H, 8.34. Found: C, 82.98; H, 8.21. Reactions of trans-1,d-dimesitoylcyclopentane. ( a ) With sodium ethoxide. Six-hundredths of a gram of sodium was added t o 4 ml. of absolute ethanol. When the reaction was complete, the solution was added t o 1 g . of 1,2-dimesitoylcyclopentanedissolved i n 50 ml. of dry benzene. There was no color change a t first but, after the solution had stood a t room temperature for twelve hours, i t became dark red. It was allorved t o stand a t room temperature for ten days, and was acidified with acetic acid, washed with water, with saturated
SYNTHESIS O F FULVENES
127
sodium bicarbonate and with water. The benzene was removed by distillation from a steam-bath, the last traces being removed under diminished pressure. Crystallization did not take place from ethanol. However, several recrystallizations from high-boiling petroleum ether gave orange-brown plates, m.p. 250-251", with decomposition. Anal. Calc'd for C25H2802: C, 83.76;H , 7.31. Found: C, 83.74;H, 7.28. This product decolorized bromine water and was insoluble i n sodium hydroxide. (0) With alkali. One gram of 1,2-dimesitoylcyclopentane was heated strongly with a 40Yc solution of sodium hydroxide. The diketone did not dissolve. One gram of 1,2-dimesitoylcyclopentanewas heated with 3 ml. of diethylene glycol, 0.5 g. of potassium hydroxide, and 0.5 ml. of water. The diketone did not dissolve before the decomposition of the diethylene glycol took place. Preparation of trans-l,2-dibenzoyEcyclopentane. Eleven and eix-tenths grams of the acid chloride of trans-l,2-cyclopentanedicarboxylicacid was dissolved i n 100 ml. of dry, thiophene-free benzene. I n the course of two hours 18 g. of anhydrous aluminum chloride was added, slowly and with vigorous stirring, to the reaction mixture. The solution was heated under reflux for a n additional two hours. The mixture was decomposed n-ith ice and hydrochloric acid and the benzene was removed by steam distillation. The residue i n the flask was extracted with ether and the combined extracts were washed with 5YCsodium carbon:tte solution and with water. Removal of the ether by distillation left a white solid. One recrystallization from ethanol with Norit gave 12.6 g. (76Y0)of cr-hite prisms, m.p. 90-91". After two more recrystallizations the 1,2-dibenzoylcyclopentanemelted at91-91.5". Anal. Ca!c'd for C19His02:C,81.99;H,6.52. Pound: C,81.96;H,6.74. One gram of 1,2-dibenxoylcyclopentanefailed t o dissolve i n either boiling 40% sodium hydroxide or in a boiling mixture of 3 ml. of diethylene glycol, 0.5g. of potassium hydroxide and 0.5 ml. of water. Treatment with sodium ethoxide produced a colored derivative bu, i n too small a quantity to be characterized. SUMMARY
It has been found that certain 1,2-diaroylethylenes are converted by the action of sodium ethoxide to the corresponding 1,4-diaroyl-2, 6-diaryl-6-hydroxyfulvenes. 1,2-Diaroylethanes, treated similarly, yield the same fulvenes as the corresponding ethylenes. Possible mechanisms for these transformations have been presented. URBANA, ILL.
REFEREKCES
(1) GARDNER A N D RYDOX, J . Chem. Soc., 45 (1938). (2) LUTZ,J . Am. Chem. Soc., 66, 1590 (1934). (3) KUHNA N D LEVY,Ber., 61, 2240 (1928). (4)WISLICENUS, Ber., 33, 771 (1900). (5) THIELE,Ber., 33, 669 (1900). (6) GILBERT A N D DOKLEAVY, J . Am. Chem. SOC., 60, 1911 (1938). (7) GILBERT AND DONLEAVY, J . Am. Chem.SOC.,60,1737 (1938). (8) KAYA N D PERKIN, J. Chem. Soc., 87, 1073 (1905). (9) LUTZAND KIBLER,J . Am. Chem. Soc., 62, 360 (1940). (10) LUTZA N D PALMER, J . Am. Chem. S o c . , E7, 1947 (1935). (11) COXANT AND LUTZ,J . Am. Chena. Soc., 46, 1303 (1923). AKD SCHULZE, Ber., 35, 168 (1902). (12) PEAL (13) LUTZ,LOVE,AKD PALMER, J . Am. Chem. Soc., 67, 1953 (1935). (14) FCSON A N D COLE,J . Am. Chem. SOC.,60, 1237 (1938).
