DECEMBER
1957
1565
1,5-DIARYIr2,3-PYRROLIDINEDIONES.X
from ethanol produced small white platelets of analytical benzoy1)acrylic acid'g [prepared from &(p-methoxybenzoy1)propionic acid%] was carried out as was the preparation of purity, m.p. 12&1~90. Anal. Calcd. for Cldz&O~: C, 75.87; E, 5.97; N, 5.53. XIIIc above. The product was obtained in quantitative yield: m.p. 144.5-145.0' dec. after several recrystallizations Found: C, 75.84; H, 6.02: N, 5.59. Reduction of a-anilino-r-.nhenvl-r-butvrolaetwleIVIIIa). from benzene. a - A n i l i n o - y p l ; e n y l - y b u t ~ o ~ c ~ n e ' ((258 ~ ~ I mg., a ) 1.02 A n d . Calcd. for ClsHlsNOb: C, 65.64; H, 5.82: N, 4.25. mmoles) was reduced exactly as was 5-phenyl-3-aniliio- Found: C, 65.69;H, 5.79; N, 4.25. (Y-(N-Benzoyl-p-anisylamino)-r-(p-anisy1)- ybutyrolaetone Z(5H)-furanone (Ia) above. There was absorbed 112% of one equivalent of hydrogen in 1 hr., and 200 mg. (77%) of (XV). To a solution of 1.0 g. (0.0030 mole) of XIIIb and a-anilino-r-phenylbutyric acid (VIIa) was obtained, m.p. 0.5 g. of sodium carbonate in 20 ml. of water was added 0.5 183-186' dec. (heated a t 5'/min.) after one recrystallization g. (0.013 mole) of sodium borohydride. After standing a t from ethanol. On comparison with authentic material, in- room temperature for 12 hr. acidification with acetic acid frared spectra were superimposable and the mixture m.p. precipitated the amino hydroxy acid XIV, which could not be induced to lactonbe. This hydroxy acid was dissolved in was 184-188' dec. a-(p-Anisylamino)-B-bmzoylpropionic acid (XIIIc). In warm pyridine and treated with benzoyl chloride. After a solution of 1.0 g. of sodium carbonate in 10 ml. of water warming for a few minutes, the solution was poured into was dissolved 1.0 g. (5.7 mmoles) of 8-benzoylacrylic acid excess 3% sodium carbonate solution. The XV came down and 1.0 g. (8.1 mmoles) of p-anisidine. After standing for as an oil which soon crystallized and was recrystallized from 16 hr. a t room temperature, the solution was acidified with ethanol, m.p. 157-161'. Several further recrystallizations acetic acid, precipitating an oil which soon solidified. This produced small white needles of analytical purity, m.p. was 6ltered and washed well with ether, yielding 1.3 g. (77%) 164.5-165.5' (reported" 169.5-170.0'). of XIIIc. Several recrystallizations from benzene produced Anal. Calcd. for CZJ&~NO~: C, 71.95; H, 5.55; N, 3.36. the analytical sample, m.p. 134-135' dec. Found: C, 71.82; H, 5.53: N, 3.37. When compared with the material erroneously described Anal. Calcd. for Cl~HlrNO~: C, 68.19: H, 5.72; N, 4.68. by Vaughan and Peters" as the benzoate of 1,5-di-(p-anisyl)Found: C, 67.79; H, 5.66; N, 4.53. a-(p Anisylarnino)-yphenyl-ybutyrohctme (MIIc). The 3-hydroxy-2-pyrrolidinone, this compound was found identisodium borohydride reduction of XIIIc was carried out cal in all respects, and the mixture melting point was undeby a procedure identical with that used for the preparation pressed. of VIIIa above. The product was recrystallized from ethaANNARBOB,MICH. nol, m.p. 147-148' (21%yield). Anal. Calcd. for C l ~ H l ~ N OC,~ :72.07: H, 6.05; N, 4.94. Found: C,72.01; H, 6.02; N, 4.93. e( p - A n i s y ~ m i n o ) - ~ - ( p t ~ z y ~ ~ zacid ~ l ) p r(29) o ~ L. ~ F. Fieser and E. Hershberg, J . Am. Chem. Soc., 58, (XIIIb). The addition of panisidine to 8-(p-methoxy- 2314 (1936).
[CONTRIBUTION FROM
THE
DEPARTMENT OF CHEMISTRY OF THE UNIVERSITY
OF
MICHIGAN]
1,5-Diaryl-2,3-pyrrolidinediones.X. Phenylhydrazine Derivatives WALTER L. MEYER'
AND
WYMAN
R. VAUGHAN
Received May 17,1967 Structures of two of the three products of the reaction of 5-phenyl-3-anilino-2(5H)-furanone(I) with phenylhydrazine have been reassigned. One of these, 1,5-diphenyl-2,3-pyrrolidinedione-3-phenylhydrazone(XI) was found to be tautomeric with benzylidenepyruvanilide phenylhydrazone (IX), a new type of tautomerism for which the term "lactam-enamide" is proposed.
5-Phenyl-3-aniliio-2(5H)-furanone (I), the compound formerly described as 1,5-dipheny1-2,3-pyr- tion of I1 as I,6which may isomerize reversibly to rolidinedione (11), affords three distinct products 111, has made a re-evaluation of these derivatives on treatment with phenylhydrazine.2-6 These desirable. compounds, A, B, and C, have been variously forcas CBH~ mulated in the literature, but inasmuch as they have been considered derived from and analogous to I1 "Cas 0 (which was an incorrect structure), the reformula-
yo g-:
( 1) National Science Foundation Predoctoral Fellow, 1954-1957. Abstracted from a portion of the PbD. dissertation of Walter L. Meyer, University of Michigan, 1957. (2) S. Bodforss, Ann., 455, 41 (1927). (3) H. Bucherer and.R. Russischwili, J . prukt. Chem., 128,89 (1930). (4) W. R. Vaughan and D. I. McCane, J . 079. Chem., 20, 143 (1955). (5) W. R. Vaughan, J . Org. Chem., 20, 1619 (1955). (6) (a) W. L. Meyer and W. R. Vaughan, J . Org. Chem., 22, 98 (1957). (b) W. L. Meyer and W. R. Vaughan, J . Org. Chem., 22, 1560 (1957).
I
I1
N-CBHs II
CF,H,CH=CH-C-CO~ I11
The simplest of the reaction products of I with phenylhydrazine is A, first obtained by Bucherer and Russischwili3and later examined by Vaughan and M ~ C a n eThis . ~ substance, A, has the molecular formula C16Hl4N202, and arises by substitution of aniline by phenylhydra~ine.~ By analogy with the
1566
VOL. 22
MEYEB AND VAUGFIAN
isomeric structures I and 111,6the readily reversi- 1,5-diphenyl-2,3-pyrrolidinedione(11) under conble isomerism4 of A should now have its members ditions normally used for phenylhydrazone formarepresented by IV and VI rather than IV and V. tion, which also supports its formulation as XI. Consequently for B a choice between the strucN- "Cs& tures IX and XI becomes possible on consideration /I of the following observations (Chart I). CeHSCH=CH- C-CO2H When unsolvated, B contains only one absorp 1V tion band in the NH region of the infrared. This C6&G-:C&6 is consistent with XI, but not IX or the enamine form of XI (XII), either of which should have two G o such bands. This is not conclusive, of course, as the 0 NNHG& V
VI
N-CeHs
c6H5T+0
The second product from the interaction of I with phenylhydrazine, B,2--6is not so readily formuN HNHC 6 lated. When unsolvated it is found to have the xIr formula C Z Z H ~ ~ N and ~ Ohas , ~been assigned several structures in the past which are of little conse- two absorptions of IX or XI1 might fall at the same quence in the light of recent knowledge of the struc- frequency. The phenylhydrazone B is formed from I1 and ture of I. Thus a complete re-examination of the phenylhydrazine in warm ethanol containing a few properties of B is necessary for its accurate formudrops of acetic acid. Under identical conditions, lation (Chart I) benzylidenepyruvanilide (VII) and phenylhydrazine afford only the pyrazoline VIII, whereas withCHART I out acetic acid, B is the sole product from VI1 and STRUCTURE PROOF OF XI phenylhydrazine. That B is obtained from I1 but not VI1 in the presence of acid indicates that the pyrazoline is much more readily formed from the primary reaction product of VI1 and phenylhydraNHCeH6 zine than it is from B itself. Therefore, B is not the x initial reaction product from VI1 and phenylhydrazine. In consideration of the compounds from which it is formed and the extreme ease of isomerization of this initial product to the pyrazoline, it is reasonable to formulate it as benzylidenepyruvanilide phenylhydrazone (IX); this can account for a11 these observations. IX It having been argued that IX is the initial prod. \ uct of reaction of VI1 with phenylhydrazine, there remains no objection to the formulation of B as XI. Indeed, it would be highly unlikely that XI would isomerize to the pyrazoline more readily than does IX, which formulation of B as IX would require. That XI is isomerized to the pyrazoline VI11 under more vigorous conditions implies its intermediate conversion to IX, and since in the absence of acid, The material (B) is also obtained from benzyli- benzylidenepyruvanilide and phenylhydrazine prodenepyruvanilide (VII) and phenylhydrazine6 and duce XI, from the initial product (IX)it is sugmay be isomerized to 1,5-diphenyl-AZ-pyrazoline-3- gested that IX cyclizes to XI. This implies a recarboxaiiilide (VIII). This suggested a t least po- versible isomerism between XI and IX, XI being tential existence as benzylidenepyruvanilide phen- the normally stable form of the pair, but IX being ylhydrazone (IX). However, B is obtained from the able to react irreversibly (pyrazoline formation) and force the reaction to proceed in its favor. pyrrolidinedione anil (X) and phenylhydra~ine,~,~,~ suggesting replacement of anil by phenylhydra~one~ The reversible isomerism between XI and IX apt o give 1,5-diphenyl-2,3-pyrrolidinedione-3-phen-pears to be an unique example of the type. It is IV, but inylhydrazone (XI). B is also formed from the true similar to that of I e 111 and of VI volves the corresponding nitrogen functions (lac(7) Such a substitution is known to occur on X with tam and anilide). There is no reason to believe this hydroxylamine, although under somewhat different condi- cannot occw, since as with known types of ring~
tions.8 Likewise, other aromatic amines have been used to substitute for the anil aniline of X,* although the characterization of these products w m not complete.
__-
(8) W. L. Meyer and W. B. Vaughan, J . Org. Chem., 22, 1554 (1957).
DECEMBER
1957
1,5-DIARYL-2,3-PYRROLIDINEDIONES. X
chain tautomerism, the analogous intermolecular reactions are well known. I n this case the Michael addition and its reverse of weak acids to a conjugated double bondg represents the intermolecular reactions. That this reversible cyclization is much less facile than that of I with 111,also found in this series, is to be expected, since the ring-opening reaction here produces a much stronger base (the anilide anion), and thus constitutes an energetically more difficult process. Such apparently tautomeric behavior, suggests the reason the elusive anil of benzylidenepyruvanilide has not been observed. All attempts to obtain this substance (XIII) have resulted in isolation of the pyrrolidinedione anil X.lo I n the anil XIII, no alternate cyclization reaction such as IX undergoes to the pyrazoline, is available and thus its existence has not been demonstrated.
NOR
XI11 NOR
XIV: R=H
XV: R=H
XVI: R = C C H ~
This lactam-enamide tautomerism is not a general behavior of the compounds in this series, however. Thus benzylidenepyruvanilide (VII) and 1,5-diphenyl-2,3-pyrrolidinedione(11) are distinct compounds, as are the corresponding oximes (XIV and XV) and oxime acetates (XVI and XVII). Although extensive attempts have not yet been made to interconvert these forms, it was definitely observed that the cyclization reactions were not spontaneous as seems to be the case for the anil and phenylhydrazone. Further research on the factors governing t,his reversible cyclization is in progress. The third product from the reaction of I with phenylhydrazine contains two phenylhydrazine residues and has been formulated as XVIII or XIX.2v6At present, as pointed out by Vaughan,6no choice between these formulations exists. N-NHC5I-15
II
CeHsCH=CH- C-CNHNHC&
II 0 XVIII
C6H5T
o HceH6
NNHCBH~ XIX
(9) C. K. Ingold, Structure and Mechanism in Organic Chemistry, Cornel1 University Press, Ithaca, New York, 1953, pp. 690-6. (10) L. R. Peters, Ph.D. dissertation, University of Michigan, 1952.
1567
EXPERIMENTAL
All melting points are uncorrected. Microanalyses are by Spang Microanalytical Laboratory, Ann Arbor, Mich. Infrared spectra were recorded from Nujol mulls, unless otherwise noted, by means of a Perkin-Elmer Model 21 Infrared Spectrophotometer. 1,5-Diphenyl-~,S-pyrrolidinedione-S-phenylhydra~one(XI). ( a ) Frona 1,&diphen yl-J-anilino-d( 5H)-pyrrolone (X). The anil X and phenylhydrazine were heated together according to the directions of Bodforss2 to produce XI, m.p. 128-131" dec. after several recrystallizations from ethanol (monoethanolate, reported6 131-132" dec.). A sample of this material was de-ethanolated by heating in xylene according to the directions of Vaughan.6 The unsolvated material had but one band, a t 3220 em.-], in the high frequency region of the infrared spectrum. On recrystallization from ethanol it was reconverted to the ethanolate. ( b ) From 1,6-diphenyl-2,S-pyrrolidlnedione (11).To 50 mg. (0.20 mmole) of I1 in 4 ml. of ethanol containing 3 drops of acetic acid was added 5 drops of phenylhydrazine and the solution was warmed for 30 see. on the steam bath. The product, which precipitated after 6 hr. a t room temperature, was recrystallized from absolute ethanol to m.p. 128131' dec., which was undepressed on admixture with the material obtained by procedure a above. The infrared spectra of the samples from the two procedures were identical. This compound gives a blue color on application of the Knorr pyrazoline test, which fades after several hours, as described by Vaughan.6 1,5-Diphenyl-A2-pyrazoline-3-carboxanilide (VIII). A solution of 50 mg. (0.20 mmole) of benzylidenepyruvanilide (VII)11 in 4 ml. of ethanol was treated with acetic acid and phenylhydrazine precisely as was I1 in procedure b above. After standing for 6 hr., no crystallization had occurred. Addition of water threw down an oil which was crystallized from ethanol. The pale yellow solid melted a t 189-194'. Several more recrystallizations raised the m.p. to 197-198" (reported 203-204").5 The infrared spectrum of this sample was identical with that of the authentic material,' and a mixture melting point was undepressed. This substance gives a bright emerald green color on application of the Knorr test as described by Vaughan.6 Benzylidenepyruvanilide oxime (XIV). To a solution of 181.8 mg. (0.725 mmole) of benzylidenepyruvanilide (VII) in 20 ml. of absolute ethanol was added 77.0 mg. (1.12 mmoles) of hydroxylamine hydrochloride, and the solution was refluxed overnight. Following the cooling of the solution to room temperature, an equal volume of water was added, throwing down a white precipitate. This was filtered and amounted to 134 mg. (707,) of XIV, m.p. 201-207" dec. Several recrystallizations from ethanol produced the analytical sample, m.p. 203.5-204.5' dec. (highly dependent on rate of heating). Anal. Calcd. for C16H14X202: C, 72.1G; H, 5.30; N, 10.52. Found: C,72.10; H, 5.37; iY,10.42. The oxime acetate was prepared by the use of acetic anhydride in acetic acid, m.p. 144.0-144.5' after recrystallization from ethanol. Anal. Calcd. for C1dhN203: C, 70.11; HI 5.23. Found: C,70.36; HI 5.43. Both the oxime and its acetate are definitely different from the corresponding 1,5-diphenyl-2,3-pyrrolidinedione derivatives (XV, m.p. 229-230" dec. and XVII, m.p. 190192' dec.).'O ANNARBOR,MICH. ~~
(11) W.R.Vaughan and L. It. Peters, J. Org. Chem., 18, 393 (1953).
