ACID-CATALYZED REARRANGEMENT OF PHENYLETHYNYLCARBINOLS 3395
July 20, 1956
[CONTRIBUTION FROM THE
LABORATORY O F ORGANIC CHEMISTRY OF THE UNIVERSITY
O F WISCONSIN]
The Acid-catalyzed Rearrangement of Phenylethynylcarbinols BY EDWARD E. SMISSMAN,~ RUSSELLH.
JOHNSEN,
ARTHURW. CARLSON AND BEN F. AYCOCK
RECEIVED DECEMBER 5 , 1955 The acid-catalyzed rearrangements of five phenylethynylcarbinols, which are capable of rearranging by either the Rupe or Meyer-Schuster mechanisms, have been investigated. The course of rearrangement and structure of the products have been determined. It has been demonstrated that a methoxyl group in the para position of a phenylethynylcarbinol is capable of changing the course of hydration of the Rupe rearrangement intermediate.
Acetylenic carbinols, R1--CC-C(OH)RzR3, apparent that the ketone produced is 1-phenyl-3,4have been reported to undergo a t least two differ- dimethyl-3-pentene-2-one (phenylacetyltrimethylent types of rearrangement on treatment with acidic ethylene) (VIII) . Reverse aldolization of this reagents. These reactions are now well known as rearrangement product yielded ethyl benzyl ketone the Meyer-Schuster and Rupe rearrangement^.^-' and acetone. The Meyer-Schuster rearrangement has been posCH3 CHa tulated to proceed through the formation of an alI 1 \ -C=C-C-CH-CH3 -+lenic carbonium ion intermediate, while the Rupe reaction has been shown to form a vinylacetylene d H VI intermediate.? The purpose of this work was to investigate the CH3 CH3 course of rearrangement in molecules which were o--C=C--:C-CH3 I / -+ Hz0 capable of both the Meyer-Schuster type reaction (formation of an allenic intermediate) and the Rupe type reaction (formation of a vinyl acetylene intermediate). OCHaCHo The compounds utilized in this study were @CHzC~;~--CH~ Ill I methylethyl-(phenylethynyl)-carbinol (Ia), methylisopropyl-(phenylethyny1)-carbinol(VI), t-butyl(phenylethyny1)-carbinol (IXa), methylethyl-@ The rearrangement of t-butyl-(phenylethynyl) methoxyphenylethynyl) -carbinol (Ib), and t-butyl(P-methoxyphenylethynyl) -carbinol (IXb) . carbinol (IXa) was conducted by refluxing with a Methylethyl-(phenylethynyl) -carbinol (Ia), on large excess of 88% formic acid under a nitrogen treatment with 88% formic acid, rearranged to atmosphere for a period of 8 hr. A mixture of isoyield an unsaturated ketone. Ozonolysis of this meric ketones was obtained in about 75% yield. ketone yielded acetaldehyde and phenylacetic The first evidence of the identity of the compoacid, the latter arising from a cleavage of benzyl nents of the mixture was obtained from the ultramethyl glyoxal. This demonstrated the rearrange- violet absorption spectra. Two poorly defined maxment product to be 1-phenyl-3-methyl-3-pentene-2-ima were evident a t 243 and 250 mM in isooctane. one (IIIa) These maxima are near the absorption maxima ex-
0
CHI ~-c=C$,,,~cH,
x / '
I
CHa
-+ H+
o-C=C-i--CHzCH3
x/
CHa
-+
/
a, X = Hb, X = CHaO-
The rearrangement of methylisopropyl-(phenylethynyl)-carbinol (VI) under similar conditions afforded an a$-unsaturated ketone in 75y0 yield. On degradation by means of ozonolysis, acetone and phenylacetic acid were produced. Thus i t is (1) College of Pharmacy, University of Wisconsin, Madison, Wisconsin. (2) K. H. Meyer and K . Schuster, Bey., 66, 819 (1926). (3) H. Kupe, e l a!., Heiv. Chim. Acta, 11,9G5 (1928); 14,193 (1929); 1 4 , 687 (1931); 16, 685 (1933). (4) F. G. Fischer and K. Lowenberg, Ann., 476, 203 (1929). ( 5 ) C. D. Hurd and R. E. Christ, T R IJOURNAL, ~ 69, 118 (1937). (6) J. D. Chanley, ibid., T O , 244 (1948). (7) G. F. Hennion, e t al., ibid., 71, 2813 (1949); 7 7 , 3253 (1955).
hibited by phenylacetyltrimethylethylene (VIII) (245 mp) and pivalacetophenone (XIIa) (250 mp), respectively (see next set of formulas). The mixture of unsaturated ketones was hydrogenated to the saturated ketones over 5% palladium-on-strontium carbonate. The ultraviolet absorption spectrum of the hydrogenated material (A, 238 mp) was similar to the spectrum of y , y dimethylvalerophenone, the hydrogenation product of pivalacetophenone (XIIIa) . The hydrogenation product of phenylacetyltrimethylethylene (VIII) would not be expected to exhibit intense
E. E. SMISSMAN, R. H. JOHNSEN, A. W. CARLSON AND B. F. AYCOCK
3396
CHa CHs
I
I
-CZ&-C=C-CHS
Vol. '78
formed through a reverse aldol condensation of the unsaturated ketone, Vb. The structure of the product of rearrangement was indicated by ozonolysis to be Vb in that the products were anisic acid and methyl ethyl ketone. The compound absorbed one mole of hydrogen to produce a saturated ketone which was identical with the ketone synthesized from 0-methylvaleroyl chloride and anisole by the method of Wilds and Biggerstaff .9
Discussion
-1 CHa
XI1
XI
a, X = Hb, X CHsOE
absorption in this region, since the carbonyl group is not conjugated with the benzene ring. The infrared analysis indicated pivalacetophenone phenylacetyltrimethylethylene and ethyl benzyl ketone to be present in the reaction mixture in mole percentages of 24, 59 and 7, respectively. These concentrations of the products in the rearrangement mixture, in conjunction with the yield, indicate that the isomeric unsaturated ketones, X I I a and VIII, were originally formed in yields of 24 and 47%, respectively. The formation of phenylacetyltrimethylethylene is explained by a Wagner-Meerwein shift of a methyl group prior to formation of the vinylacetylene intermediate. The allenic type intermediate must occur if the alkyl migration does not take place. The latter would give rise to pivalacetophenone. t - Butyl - (p - methoxyphenylethynyl) - carbinol (IXb) in the presence of SS% formic acid rearranged to form p-methoxypivalacetophenone (XIIb) in S5% yield. The structure of the ketone was established on the basis of the ozonolysis products anisic acid and pivalic aldehyde. The rearrangement product was also synthesized by an aldol condensation of pivalic aldehyde and p-methoxyacetophenone. On treating methylethyl-(9-methoxyphenylethyny1)-carbinol (Ib) with SS% formic acid, the principal product was a tar. A more dilute acid (44y0)gave the vinyl acetylenic material, IIb, as the chief product. The structure of the dehydrated carbinol was established by the formation of anisic acid and acetaldehyde on ozonolysis and by its characteristic ultraviolet absorption.8 I n the presence of glacial acetic acid containing about 1% concentrated sulfuric acid a t 70-SOo for 20 minutes, methylethyl-(p-methoxyphenylethyny1)-carbinol (Ib) rearranged to l-p-methoxyphenyl-3methyl-2-pentene-1-one (Vb) in 45% yield. The ketone was accompanied by varying amounts of the enyne, IIb, depending upon the period of reaction. When the reaction was allowed to proceed for 15 hr., there was 5-6y0 p-methoxyacetophenone present in the reaction mixture. This material was (8) 1. Heilbron, at ol.,
J. Cham.
Sor., 1583 (1947).
The results of the experiments involving t-butyl(p-methoxyphenylethyny1)-carbinol(IXa) are to be contrasted with those obtained for t-butyl(phenylethynyl)-carbinol (IXb). For the latter compound it was shown that the primary reaction product resulted from the initial migration of a product which would be expected if the Rupe type mechanism had been involved. I n the case of the methoxy compound the rearrangement product can be explained by assuming that the methoxy group suppresses the tendency of the carbonium ion formed to stabilize itself by the migration of a methyl group. The ketone which then results is that which would be predicted if the MeyerSchuster rearrangement were to take place. I n the case of methylethyl-(p-methoxyphenylethynyl)-carbinol (Ib), the situation is more complicated. The product obtained is that which would result from an allenic type intermediate, i.e., a Meyer-Schuster rearrangement. However, the compound devoid of the para-methoxyl group underwent only the Rupe rearrangement. The postulated intermediate in the Rupe rearrangement is the enyne arising by dehydration of the carbinol. The ketonic product results from the hydration of the triple bond of this interniediate. The vinyl acetylenic compound, IIb, isolated in the present work, could be converted to the unsaturated ketone, Vb, by further treatment with acid, but the resulting ketone has the structure anticipated on the basis of a Meyer-Schuster rearrangement rather than that associated with the Rupe for which such an intermediate is postulated. This leads to the conclusion that the para-methoxyl group causes a polarization of the acetylenic bond in the enyne intermediate so as to allow hydration to occur a t the carbon atom adjacent to the ring.
Experimental Preparation of Methylethyl-(phenylethynyl'i-carbinol(Ia). -Thirty grams (0.294 mole) of phenylacetylene and 22.0 g. (0.305 mole) methyl ethyl ketone were added to 100 ml. of absolute ether. The flask was cooled to O", while 20 g. of potassium hydroxide pellets were being powdered under ether. The powdered potassium hydroxide was added t r i the flask. The reaction mixture was stirred mechanically for 11 h r . and allowed to stand overnight a t 0". The mixture was transferred t o a large beaker and mixed well with powdered, solid carbon dioxide, after which the solution was filtered from the precipitated potassium carbonate. T h e ether was removed and the residue was distilled in wucuu. T h e fraction boiling at 151-151.' (30 mm.) was collected, 38.29 g. (74.4%) of a clear viscous liquid (lit. b.p. 138-140' (15 ".)lo (9) A. L. Wilds and W. R. Biggerstaff, THISJ O U R N A L , 67, 780 (1945). (10) Bork, J . R I N . P.C. Sor., 37, (190:); B d . Chcm. A h . , I , 774. (1905).
July 20, 1956
ACID-CATALYZED REARRANGEMENT OF PHENYLETHYNYLCARBINOLS 3397
Preparation of Methylisopropyl-(phenylethynyl)-carbinol to stand at room temperature for 30 minutes. I n the mean(VI).-Twelve grams (0.5 mole) of magnesium and 73 g. (0.7 time a solution of 48.0 g. (0.666 mole) of redistilled methyl mole) of ethyl bromide were allowed to react in 100 ml. of ethyl ketone (b.p. 78-80') in 250 ml. of anhydrous ether anhydrous ether. After the reaction had subsided, 61 g. was cooled to -10'. The solution of potassium acetylide (0.6 mole) of phenylacetylene was added and allowed to was then added dropwise, with stirring, over a period of 3 reflux for 6 hr. After cooling the reaction mixture, 34 g. hr. and the mixture stirred for an additional 9 hr. with the (0.4 mole) of methyl isopropyl ketone was added dropwise bath temperature rising during this period to 15'. At the with stirring. The mixture was then refluxed for 2 hr. end of this interval, 20 g. of ammonium chloride in 500 ml. The Grignard complex was decomposed with ice and suffi- of water was added, the aqueous phase was saturated with cient acetic acid t o form the soluble magnesium salt. The sodium chloride, separated from the ethereal layer and reexcess acid was neutralized with 10% sodium bicarbonate extracted with two 50-1111. portions of ether. The extracts and the neutral organic material extracted with two 100-ml. were combined and dried over anhydrous sodium sulfate. portions of ether. The combined extracts were washed with The ether and t-butyl alcohol were removed by distillation water and dried over anhydrous sodium sulfate. After re- a t atmospheric pressure and the higher boiling residue distilled under reduced pressure. The fraction boiling a t moval of ether, the residue was distilled. Twelve grams of unchanged phenylacetylene, b.p. 30-40' (10 mm.), was col- 165-170' (10 mm.) was collected as carbinol, 44.0 g. (75% lected. The impure product was collected, 120-135' (10 based on phenylacetylene). Redistillation afforded a prodmm.) and a residue of 14 g. of tarry material remained. 254 uct boiling at 175-176" (13 mm.), 7 t 2 6 ~ 1.5538; A,,, The impure product was redistilled through a 10-in. Vigreux mp 24,000. Anal. Calcd. for CllHleOl: C, 76.40: .. .. . column under reduced pressure yielding 60.3 g. (80%) of H., 7.g"- Found: C, 76.09; H , 7.9. carbinol, b.p. 128-132' (8 mm.), nZ6D1.5378. The liquid Preparation of p-Methoxypheny1acetylene.-To a solureadily crystallized to give a white solid mass, m.p. 42-43' tion of 13.0 g. of potassium in 600 ml. of t-butvl alcohol 240 mp, (lit. b.p. 136-137' (12 mm.), m.p. 41'), A, (which had b
