FEBRUARY
627
COMMUNICATIONS
1961
I(
N O A
v ) '
:I
'b
IUj,
7.3
9.0
4
s
IO
I
0
IO
20
30
40
60
Fig. 1. Separation of steroids with a neopentyl glycol adipate (0.75%) phase on Gas-Chrom P. The conditions and compounds are described in Table I
these may prove to be particularly useful in separation and identification work. Packings with phase concentrations ranging from 0.01 to 10% have been prepared by the filtration techniquea with these polyesters.
Products
E. 0. A. HAAHTI' LABORATORY OF CHEMISTRY OF W. J. A. VANDENHEWEL NATURAL PRODUCTS E. C. HORNING NATIONAL HEARTINSTITUTE BETHESDA 14, MD. Received November 1, 1960
(6) Visiting scientist, National Heart Institute, from the University of Turku, Finland.
Q 1
I
The Electronic Nature of the Transition State of the Claisen Rearrangement
Y:
t
11
Q Y:
Sir: Although the Claisen rearrangement has been extensively investigated, the electronic nature of the transition state has not been adequately delineated. For this reason we have made a detailed study of substituent effects on this reaction. The Transition State following representation'J is consistent with our experimental findings: The negative rhos indicate that electron depletion It has been shownathat the rearrangement rates of allyl pX-phenyl ethers are correlated by Ham- occurs in both the cinnamyl chain and the aryloxy mett's equation using up+ constants and a p of portion of the molecule as the reactant changes to -0.61 (T = 0.99). The isomerization rates of eleven transition state. The need for u+ constants shows Y-cinnamyl ptolyl ethers were determined spec- that this electron deficiency interacts directly with trophotometrically and are correlated using u+ con- the substituent by resonance. These deductions are accommodated by the stants and a p of -0.40 (r = 0.99). proposed transition state. The quasi-radical bond(1) These structures do not imply that actual scission of the molecule into radicals occurs. Structure I is simply the breaking and bond-forming involves an oxygen cinnamyl aryl ether with a stretched G O bond and the atom formally having seven electrons (I). This ?-carbon in a position to form a long bond to the ortho posi- electron-deficient, electronegative oxygen atom tion as indicated in 11. Many other contributors of the types will withdraw electrons from the aryloxy ring shown are possible. (cf. 111) and the cinnamyl group (cf. IV). The (2) The aryloxy port,ion of contributing structures I, 11, electron deficits created in this way would require 111, and IV are similar to the structures postulated to acu+ for correlation of substituent effect^.^,^ count for the stability of semiquinones (see G. W. Wheland. Advanced Organic Chemisiry, -3rd Ed.,' Wiley, New York; 1960, pp. 802,803. and 811). (3) (a) W. N. White, D. Gwynn, R. Schlitt, C. Girard, and W. Fife, J . Am. Cheni. Soc., 80, 3271 (3958); (b) H. L. Goering and R. R. Jacobson, J . Am. Chew&.Soc., 80, 3277 ( 1958).
(4) Similarly thermal cleavage of t-butyl X-phenylperacetates (P. D. Bartlett and C. Ruchardt, J , Am. Chem. Soc., 82, 3756 (3960)) required u + const.ants for correlation probably because of the electronegativity of the oxygen of the t-butaxy radical.
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COMMUNICATIONS
The proposed transition state also accounts for the accelerating effects of alkyl and aryl substitution at the CY and ?-positions in the allyl side chain. Acknowledgment. This work was supported by grants from the Research Corporation and the National Science Foundation (NSF-G-7345). DEPARTMENT OF CHEMISTRY THEOHIOSTATEUNIVERSITY COLUMBUS 10, OHIO
WILLIAMN. WHITE CARLD. SLATER WILMERK. FIFE
Received September 27, 1960
Gas Chromatographic Separation of Steroidal Amines
Sir: Recent studies in this laboratory have established that gas chromatographic methods may be used to separate naturally occurring compounds of complex structure in the ~teroidl-~and alkaloida fields. The sensitivity and resolving power of these methods is now well established; however, it is not known in these fields if structural correlations can be made from retention time interrelationships.
& p - . c HH3 cT+ Fig. 1. Hammett plots of rates of rearrangement of substituted allyl aryl ethers: 0 , allyl p-X-phenyl ethers X-cinnamyl p-tolyl ethers plotted plotted apainst up+; against o+; and 0 , rearrangement of allyl m-X-phenyl ethers to 2-allyl-BX-phenols plotted against up
+,
OH
+
HO
This picture of the activated complex also explains the unusual substituent effect in the rearrangement of allyl mX-phenyl ethers (determined spectrophotometrically2a). The rates of rearrangement to the unhindered 2-allyl-5-X-phenols were obtained by multiplying the overall rates by the fraction of this isomer formed (ascertained by isotope dilution analysis). These rates were correlated using a,+(not a,+) and a p of -0.66 (r = 0.96), which is similar to that used for the para isomem. This result is explicable if structures such as V contribute to the transition state.6 t
V
Ar
(5) f t is reported that inhibition of autoxidation by substituted phenols is correlated by u constants and a negative p D. Cook, D, C. Lane, and R. S. Stone, private comhunication) . (6) There is ho o p r i b r i reason for expecting a difference in energy between structures III and V. Simple LCAU-MO calculations indicate that the change from reactant to this transition stste involves nearly equal energy incrementa for both mda and pcra substituted isornere‘Bi +
((24
5
RCH HO
1-111
’
5
IV-IX
x-XVII
In order to investigate this point, a study was made of the gas chromatographic behavior of a series of steroidal amines derived from tomatidine (1) W. J. A. VandenHeuvel, C. C. Sweeley, and E. C. Homing, J . A m . Chem. Soc., 8 2 , 3481 (1960) (steroids). (2) W. J. A. VandenHeuvel, C. C. Sweeley, and E. C. Homing, Biochem. Biophys. Res. Comm., 3, 33 (1960) (sex hormones and bile acids). (3) W. J. A. VandenHeuvel and E. C. Homing, Biochem. Biophys. Res. Comm., in press (adrenal cortical steroid hormones). (4) W. J. A. VandenHeuvel, C. C. Sweeley, and E. C. Homing, “Separation of Steroids by Gas Chromatography,” Symposium on Drugs Affecting Lipid Metabolism, Milan, Italy, June 2-4, 1960 (sterols and sterol esters). ( 5 ) C. C. Sweelev and E. C. Homing, -, Nature,. 187, . 144 (1960) (steroids). ” (6) H. A. Lloyd, H. M. Fales, P. F, Highet, W. J. A.VandenHeuve1, and W. 6. Wildman, J. Ana, Chem, SOC.,82,
