Dec., 1951 ALLYLGROUPPHENYLMAGNESIUM BROMIDE-ALLYLISOBUTYROMESITYLENE REACTION5759 toluene, was added dropwise a mixture of sodamide (from 6.2 g. sodium) and 32.2 g. (0.255 mole) of benzyl chloride in 200 ml. of toluene. The mixture was refluxed and stirred for an additional seven hours, cooled, decomposed with water and the toluene layer separated. The aqueous layer was extracted with benzene and the combined benzenetoluene solutions were extracted several times with a 10% hydrochloric acid solution. The aqueous acid extracts were made basic with ammonia, processed in the usual manner and distilled. T o a warm, stirred suspension of sodamide (from 2.6 g. of sodium) in 200 ml. of dry xylene was added 20 g. (0.106 mole) of a-dimethylaminomethyl-0-phenylpropionitrile, followed by the cautious addition of 20 g. (0.127 mole) of 2bromopyridine. A violet reaction occurred with the addition of each increment of 2-bromopyridine. The reaction mixture was stirred and refluxed for eight hours, cooled, decomposed with water, the organic layer separated, the solvent removed and the residue distilled. Attempts to hydrolyze and decarboxylate this nitrile with 80% sulfuric acid a t 140-150° were unsuccessful. Reduction of y-Phenyl-r-(2- yridy1)-N,N-dimethylpropylamine (XII) (a) Raney N i c k e f h Methanol. 7-Phenyl-?(N-methyl-2-piperidyl)-N,N-dimethylpropylamine(XIV).A solution of 24 g. (0.1 mole) of r-phenyl-y-(2-pyridyI)-N,Ndimethylpropylamine was reduced in methanol with Raney nickel catalyst and hydrogen for four hours a t an initial pressure of 1,000 p.s.i. and a temperature of 170”. The catalyst was filtered, washed with methanol, the combined filtrates and washings concentrated in vacuo and the residue distilled t o give two fractions; fraction I, wt. 8.2 g., b.p. 105-121’ (1 mm.), n Z 91.5292; ~ fraction 11, wt. 12 g., b.p. 126-132’ (1 mm.), n% 1.5196. Fraction I1 was redistilled and boiled a t 122-125’ (0.5 mm.), nmD 1.5193. Anal. Calcd. for C I ~ H Z ~ NC, Z :78.38; H , 10.84; N, 10.84. Found: C, 78.61; H, 11-09; N, 10.88. The picrate (m.p. 200-204’) depressed the melting point of the picrate of 7phenyl-y-(2-pyridyl)-N,N-dimethylpropylamine(m.p. 2032040). Fraction I, upon redistillation, boiled a t 100-105’ (0.5 mm.), n% 1.5299. Anal. Calcd. for CISHZ~N: C, 82.87; H, 10.67; N, 6.45; and for CMHIIN: C, 82.68; H , 10.42;
[CONTRIBUTION FROM
THE
N, 6.89. Found: C, 82.42; H, 10.08; N, 6.79. On the basis of the analyses, it is apparent that the dimethylamino group had been lost. ( b ) Sodium and Alcohol. yPhenyl-y-( 2-piperidyl)-N,Ndimethylpropylamine (XV).-To a solution of 24 g. (0.1 mole) of XI1 in 190 ml. of ethanol (dried over sodium) was added 27.4 g. of sodium metal (in cubes) as rapidly as possible. After the vigorous reaction had subsided, an additional 90 ml. of alcohol was added and the solution was refluxed on the steam-bath until all the sodium had dissolved. Upon vacuum concentration, the contents of the flask solidified and water was added until an oil appeared. The latter was extracted with ether, the ether layer washed with water, dried, the solvent removed and the residue distilled. After a forerun (5.2 g.), b.p. 100-125O (0.5 mm.), the main fraction, yield 14.2 g. (58%), b.p. 127-130” (0.5 mm.), nZ% 1.5244, was obtained. Redistilled for analysis, b.p. 117120’ (0.1 mm.), n% 1.5249. Anal. Calcd. for CI~H&Z: C, 78.00; H, 10.64. Found: C, 77.44; H , 10.26. Y-Phenyl-y-( N-methyl-2-piperidyl)-N,N-dimethylpropylamine (XIV).-To 6 ml. of cooled, 90% formic acid was added 8.5 g. of y-phenyl-y-(2-piperidyl)-N,h’-dimethyIpropylamine (XV). Six ml. of 37% formalin solution was then added and the reaction mixture heated on the steambath overnight. Twenty ml. of 10% hydrochloric acid solution was added and the solution was vacuum concentrated to a residue, made basic with sodium hydroxide solution and the oil extracted with ether. The ether layer was washed with water, dried, the solvent removed and the residue distilled; yield 7 g. (78%), b.p. 127-134’ (1 mm.), n2’D 1.5231. Anal. Calcd. for C I ~ H Z ~ NC, Z : 78.42; H, 10.84. Found: C, 78.63; H , 10.60. The picrate melted a t 204-205’ and when mixed with the picrate of y -phenyl - y - (N-methyl-2-piperidyl) - K,N - dimethylpropylamine (m.p. 202-204’), obtained from the reduction of ~-phenyl--p(2-pyridyl)-N,N-dimethylpropylamine with Raney nickel and hydrogen in methanol, melted a t 203-204”. However, a mixed melting point with the picrate of 7-phenyl-?-( 2-piperidyl)-N,N-d imethylpropylamine (m.p. 204-205’) was depressed, m.p. 192-193’. BLOOMFIELD, YEWJERSEY RECEIVED JUNE 9, 1951
DEPARTMENT OF CHEMISTRY, UNIVERSITY OF CALIFORNIA 1
The Displacement of the Allyl Group in the Reaction between Phenylmagnesium Bromide and a-Allylisobutyromesitylene BY T. A. GEISSMAN AND ROBERT M. HOROWITZ a-Allylisobutyrornesitylene is cleaved by phenylmagnesium bromide in ethyl ether solution a t 125-135’ to yield allylbenzene and isobutyromesitylene. In isoamyl ether a t 125’ but in the presence of traces of metallic magnesium the reaction takes a different course and appears to proceed with the intervention of free-radical intermediates.
The “enolization” of carbonyl compounds and the removal of halogen from a-halocarbonyl compounds by the action of Grignard reagents are well-known reactions1 which appear to be closely related. Equation (1) represents the general reaction, which appears to involve a nucleophilic displacement on hydrogen or halogen by the group R of the Grignard reagent
R-COCHBrCOOEt
(1) See F. Runge, “Organo-Metallverbindungen,” Stuttgart, 1944, Edwards Bros., Inc., Ann Arbor, Mich., 1945, p. 383. (2) B. W. Howk and S. M. McElvain, THISJOURNAL, 66, 3375 (1933).
(3) D. Ivanov and A. Spasov, Bull. SOC. chim., 14) 49, 375 (1931); 151 1, 1419 (1934). (4) H. Gilman. “Organic Chemistry,” Vol. I, John Wiley and Sons, Inc..New York, N. Y.,1943, p. 499.
RCOC=CBrCOOEt
I
OH
I
+ R-C=CHCOOEt I OBr
(2)
I1
Since, however, Grignard reagents can “enolize” carbonyl compounds which contain no detectable amount of and replace active hydrogen in R’COCHpY RMgX +(R’COCH2)MgX RY (1) compounds such as acetylenes, sulfones, indene, (Y = H, halogen) et^.,^ there appears t o be no reason to dismiss the The details of this reaction are obscure. It has more general alternative that hydrogen and halogen been suggested2 that the actual species upon which may be displaced from carbon directly. It is convenient to correlate reactions of this the displacement occurs are in the case of an abromo-@-ketoester, the enol form (I) and the anal- kind with certain other reactions involving Grignard reagents, for which “cyclic mechanisms” ogous hypobromite form (11)
+
+
Vol. 73
T. A . GEISSMAN AND ROBERT h i . HOROWITZ
5760
have been proposed,6 and to write reaction (1) in the following way (2)6
I I
R‘COC-Y
+ RMgX x I
mesitylene) which was cleaved by hot 85% phosphoric acid’ to a,a-dimethylvaleric acid. Further evidence for the structure of I11 was secured when i t was found that allylmagnesium chloride could be added to I11 with the formation of a carbinol.s The results of the experiments in which I11 was allowed to react with phenylmagnesium bromide are summarized in Table I and can be summarized briefly as follows. (1) There was evidence that in all cases in which ethyl ether was used as the solvent, cleavage t o allylbenzene and isobutyromesitylene occurred. Appreciable yields of allylbenzene were obtained only when the temperature of the reaction was raised above 100’ by distillation of most of the solvent. The best yield was obtained in run 6 where the highest ratio of Grignard reagent to ketone and the highest temperature were used. (2) In isoamyl ether solution the reaction took a complex and entirely different course. In this case alone was the unfiltered reagent, containing residual traces of unreacted magnesium, used. The reaction between 111 and phenylmagnesium lxomide in ether a t 125-135O appeared to proceed in the anticipated manner according to equation
Such a formulation is preferable to one which depends upon such unsupported postulates as (a) an attack upon Y of a free carbanion ( R r ) , or (b) a preliminary ionization of Y* followed by a n electrophilic attack of this species upon RMgX. In the formulation according to equation (3) the increased electrophilic character of the carbonyl carbon atom in the complex would aid in the release of Y t o the attacking group R. These considerations suggested that a carboncarbon bond (the C-Y bond) might undergo cleavage provided that (a) a group Y were chosen from among those known to be highly susceptible to nucleophilic attack, (b) the competing reaction (4 “” CHI of addition t o the carbonyl group were suppressed // I by appropriate substitution and (c) the a-carbon CI€?--=-CO -C-CH2CH=CH2 f CeH,hlgBr -+__ atoms carried no enolizable hydrogen atoms. I \ The compound chosen for study was a-allylCHZ CH3 isobutyromesitylene (111), which was prepared 111 by the allylation of isobutyromesitylene in the CHJ~ presence of sodamide. Since enol ethers undergo CH-D-CO-C 1 1 MgBr ( 4 ) cleavage by Grignard reagents, and in the present __ case the formation of allylbenzene and isobutyro\cI3, CI H 3 tJ mesitylene would be the anticipated result of the reaction between phenylmagnesium bromide and CsHbCHnCH=CHz the allyl ether of the enol form of isobutyromesitylene, i t was necessary to establish beyond doubt and may be regarded as constituting new evidence that the allylation product I11 was indeed the C- for the mechanism of the reaction as postulated allyl derivative and not the enol ether. This was in general terms in equation 3. T h a t the cleavage established in two ways: (1) treatment of the of I11 is preceded by its rearrangement into the allyl compound with sulfuric acid in acetic acid did not ether of the enol form of isobutyromesitylene result in loss of the allyl group; and (2) the reduc- is highly unlikely, as judged from known values of tion of I11 yielded a product (a-n-propylisobutyro- the AH values for reactions of the general class
/CH3
+
\
CIIS
cH3
CH,
CHI ( 5 ) (a) R. M Horowitz, Ph.D. Thesis, University of California, Los Angeles, 1949; (b) R. T. Arnold, rt a!., THISJOURNAL, 68, 3444 11941): 64. . .87.. 337 (1945): ( c ) T. R. Tohnson. {bid.. 66. , 2875 (1942): 3029 (1933); (d) F. C. Whitmore and R. S. George, paper presented to Organic Division, American Chemical Society, Atlantic City, N. J.. 102nd Meeting, September, 1941; (e) C. G. Swain and H. B. Boyles, THIS JOURNAL, 78, 870 (1951). ( 8 ) The halomagnesium enolate is written as an 0-enolate for brevity’s sake. It is probably best represented a s a complex in which the M g X + moiety is ionically hound to the two electrons occupying an orbital surrounding C-C-0. ~~~~
I ,
~
~
represented by equation ( 5 ) 9 the equilibrium of which is substantially completely on the side of the carbonyl form. (7) A. m a g e s and C. Lickroth. Ber., 32, 1549 (1899). ( 8 ) C j . ref. 12. (9) (a) L. Pauling, “The Nature of the Chemical Bond,” 2nd Ed., Cornell University Press, Ithaca, N. Y.,1941, pp. 53, 131. (b) G.E. K. Branch and M. Calvin, “The Theory of Organic Chemistry,” Prentice-Hall, Inc., New York, 1941, p. 289.
Dee., 1951 ALLYLGROUP PHENYLMAGNESIUM BROMIDE-ALLYLISOBUTYROMESITYLENE REACTION5761 TABLE I REACTION OF a-ALLYLISOBUTYROMESITYLENE (111) WITH PHENYLMAGNESIUM BROMIDE Moles
C 6H6M gBr Solvent
Expt.
mole I11
Temp., OC.
Time, hr.
1
1.1
Ethyl ether
36-40
3
2
1.5
Benzene-ethyl ether
75
6
3
2.0
Ethyl ether
36-40
42
4
2.0
Ethyl ether"
75
43
5
2.0
Ethyl cther"
110-125
5.3
6
2.5
Ethyl ether"
125-135
3.5
7
2.0
i-Amyl ether
125
2
a Temperature attained by concentration of reaction mixture by distillation. of biphenyl and tarry distillation residues. See text for description.
