COMMUNICATIONS TO THE EDITOR
6414
ture, crude, crystalline anhydroactidione. After one recrystallization from aqueous ethanol analytically pure material, m.p. 130-133', [ a r l Z s ~-12.7 (c = 3.7, CHC13), was obtained in 46% yield. Exhaustive recrystallizations from aqueous acetonitrile afforded a single isomer of anhydroactidione, m.p. 139-141', [ a r I z 5 ~ -33.2 (c = 1.7, CHCl,), ultraviolet maximum a t 240 mp (log B = 3.94) in ethano1,'O (Anal. Calcd. for C16H21N03: C, 68.41; H , 8.04; N , 5.32. Found: C, 68.55; H, 8.29; N, 5.25). This compound, by comparison of melting points and mixture melting points, infrared (potassium bromide disk) and ultraviolet spectra, and optical rotations, proved t o be identical with authentic anhydroactidione, prepared by dehydration of Actidione with phosphorus pentoxide,2 or with an aqueous solution of hydrochloric acid and acetic acid. In both cases repeated recrystallizations from aqueous ethanol were required to yield the pure isomer melting a t 139-141'. For comparison, racemic anhydroactidione was prepared. Hydrogenation of 2,4-dimethylphenoll1 followed by dichromate oxidation2 yielded dl2,4-dimethylcyclohexanone, b.p. 53-54' (8-9 mm.), n 2 51.4430, ~ semicarbazone (96y0 yield) melting a t 188-189°.12 The relationship of this ketone with the alkaline degradation ketone already has been demonstrated.2 Then essentially following the procedure outlined above, there was obtained racemic anhydroactidione, m.p. 118-120', ultraviolet maximum a t 240 mp (log c = 3.99), infrared spectrum (chloroform solution) identical with that of enantiomorphic anhydroactidione (Found : C, 68.33; H, 7.97; N, 5.33). The key step, namely, the condensation of an aldehyde (111) with the anion of an a-formyl ketone (V), exemplifies an interesting approach to the a$-unsaturated ketonic moiety, and will be amplified in a full paper. The author expresses his warm appreciation to Dr. Coy W. Waller and members of the Chemistry Staff at Mead Johnson, to Professor D. H. R. Barton, and to Professor John W. Huffman for helpful and stimulating discussions. (10) 64,76 bodied (11) (12)
Woodward's ultraviolet rule (R. B. Woodward, THIS J O U R N A L , (1942)) predicts this value for the a,D-unsaturated ketone emin anhydroactidione. H. E. Ungnade and A. D. McLaren, i b i d . , 66, 118 (1944). D. Capon'and co-workers, Brrli. SOC. chim., 837 (1958).
Vol. 82
was applied. A radioactive labelling technique had to be used in studies of the exchange reactions CH31 CH3 and CH3Br CH3. The results are summarized in Tables I and 11. They show clearly the expected reactivity gradation in the series MeX, EtX, iso-PrX and t-BuX, as well as in the series C H Z , CH*ClX, CHClzX and CC13X. They show also that the ratio k2,1/k2,Br remains approximately constant (-9.103 for Me, l.2X103for PhCH2 and 4.6 X lo3 for CH2C1). On assumption that the entropy of activation is approximately constant (this seems to be partially justified by the data quoted in Table 11) the difference in EZ,B~- E ~ ,for I any pair RBr and RI is calculated to be about 5-6 kcal./mole, corresponding approximately to '/2 { D(R-Br) D(R-I)}, ;.e., of 11-14 kcal./mole. A similar conclusion is arrived a t from the data based on the only available example of CC13Br and CC13C1.
+
+
-
TABLE I RELATIVERATECONSTANTS FOR REACTIONS RX CH, R CHaX ( k z ) EXPRESSED AS RATIO k 2 / k l , WHERE kl REFERSTO THE REACTION CH3 PhCH, -+ CHa PhC& ( k l ) ; ALL DATAAT 65"
+
+ +
+
R
Br
1
H"
CI
CHa 45 -5.10-3 ..... 4 X 1.10-'* ..... 6 X 0.011 CzHs 180 ...... s-C~H~ Si0 ...... ..... 2X0.16 t-CpHo 1680 ...... ..... 1.85 PhCHZ 7560 6.5 . . . . . 3 x 0.33 CHzCl 6400 1.4 ..... ...... CHClz .... 131 ..... ...... CCla . . . . 7400 4 x 1.1 ...... CPS 20,000 ..... ...... a Extrapolated from results reported by Steacie (see Steacie's "Atomic and Free Radical Reactions"). * Using recent data by Dainton, Ivin and Wilkinson, Trans. Faraday SOL,55, 929 (1959), a value of 4 X 5.10-6 is obtained.
TABLE I1 RI f Me -+ R MeT . . . kz PhCHs Me + Ph.CH2 -I-MeH
+
+
R
CHa CzHs s-C~H~
- E , , kcal./mole
Er
-1.8 i 1.5 -1.9 f 1.0 - 2 . 9 f 1.0
Thi(simplenrelation
. . . k, AdAi
3
10 11
does not hold when R X is
DEPARTMENT OF SYNTHETIC ORGANIC CHEMISTRY compared with RH. As shown by the data in the RESEARCH DIVISION,MEADJOHNSON & COMPANY EVANSVILLE 21, INDIANA BERNARD C. LAWES last column of Table I, the H abstraction is relatively much faster than expected on the basis of RECEIVED IVOVEMBER 19. 1960
the high values of D(R-H)'s. Whereas D(R-H) - D(R-Br) is 30-35 kcal./mole, the calculated STUDIES OF HALOGEN ATOMS ABSTRACTION BY E2,Br are less than 2 or 3 kcal./mole if the METHYL RADICALS' assumption of a constant frequency factor is valid. Sir: I t seems that AB,/AH or AI/AH are -10-30 (see Although extensive studies were carried out on Table 11) which would make the E2,Br - E ~ , H reactions involving abstraction of hydrogen by even smaller. radicals and free atoms, very little is known about This striking observation may be accounted for those processes in which these reagents abstract in this way: The activation energy of the abstracother atoms, e.g., halogens. This note reports tion can be represented by a sum of two terms, preliminary data pertinent to reactions of the the energy required to stretch the C-X bond to its type R X CH3 + R C H Z , where X denotes length in the transition state and the repulsion I, Br or C1. I n determining the relative rate con- energy required to bring the radical to the stretched stants (k2) of those reactions our usual t e c h n i q ~ e ~ , ~
+
+
(1) This investigation was supported by the National Science Foundation.
(2) M. Levy and M. Szwarc, THISJOURNAL, 77, 1949 (1955). (3) R. P. Buckley and M. Szwarc, Proc. Roy. SOC.( L o n d o n ) , A8440, 396 (1957).
Dec. 20, 1960
COMMUNICATIONS TO THE EDITOR
C-X bond. The first term decreases along the series R-H, R-CI, R-Br, R-I as expected on the basis of decreasing D(R-X). On the other hand, the second term seems to be negligible for X-H (no repulsion between p electron of a radical and a positive H), but i t probably is considerable for X =halogen. This accounts for the reported facts. Moreover, presence of electron withdrawing groups should decredse this repulsion and increase, therefore, the reactivity. For example, although D(CH3-I) is approximately equal to D(CF3-I),4the reactivity of CF31 is greatly larger than that of CHJ, pointing to the change in the repulsion energy. The same is found when reactivities of PhCH2Br and CCLBr are compared, since again D(PhCH2-Br) D(CC13-Br).4 The effect of repulsion energy in determining the rate of halogen abstraction reactions seems therefore to be indisputable. We wish to thank Dr. John Meyer for his help in counting the radioactive samples.
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of racemization and exchange that had occurred after a short reaction period. The types of systems examined, the experimental conditions, and the results are recorded in Table I. CH3
I
X-C*-H(D)
I Y
CHy
I +- ROD(H) -+ S-C-D(H) I Base
Y
Clearly 2-octyl phenyl sulfone undergoes electrophilic substitution2 with high retention of configuration (85 to >97%) irrespective of the dissociating power of the solvent, the concentration of proton or deuteron donors, or the nature of the cation of the basic catalyst (runs 1-7). In contrast, the steric course of reaction of 2-phenylbutane and 1-phenylmethoxyethane depends markedly on these factors (runs 8, 9 and ref. 1). A third type of behavior is exhibited by 2-methyl-3-phenylpropionitrile, N,N-diethyl-2-phenylpropionamide and tert(4) A. H. Sehon and M. Szwarc, Proc. Roy. SOC.(London), A209, butyl 2-phenylpropionate. I n these systems, 110 (1951). substitution occurs with complete racemization, DEPARTMENT OF CHEMISTRY F. W. EVANS irrespective of solvent character. STATEUNIVERSITY COLLEGE OF FORESTRY Although a detailed explanation requires further AT SYRACUSE UNIVERSITY R. J. Fox SYRACUSE 10, SEW YORK M. SZWARCwork, general patterns are visible in these results. I n the first type of system exemplified by the sulRECEIVED h-OVEMBER 4, 1960 fone, the carbanion formed as intermediate is probably asymmetric, and the stereospecificity of the reEFFECT O F STRUCTURE OF CARBANIONaction is not entirely dependent on maintaining an STABILIZING SUBSTITUENTS ON asymmetric solvent envelope. The carbanion might STEREOCHEMICAL COURSE OF HYDROGENexist either as a d-orbital stabilized sp3hybrid with DEUTERIUM EXCHANGE REACTIONS A T SATURATED CARBON exchange occurring faster than inversion, or as a reSir: hybridized but still asymmetric species in which carBase-catalyzed hydrogen-deuterium exchange bon is "doubly bonded" to sulfur by p-d orbital overreactions a t benzyl carbon of optically pure 2- lap. In the latter case, formation and disposal of the phenylbutane and 1-phenylmethoxyethane previ- carbanion might occur preferentially from the same ously were reported to occur with high retention side due to steric and (or) dipoledipole interactions. of configuration in tert-butyl alcohol, and with Under such circumstances substitution could occur complete racemization in dimethyl sulfoxide. with retention of configuration.
-
TABLE I ,-----Starting Run 1 2 3 4 5 B
7 8 9 10 11 12 13
material"-
X Y n-CsHia CsHsSOl n-CaHn CsHaSOa n-CsH~a CeHaSOt n-CaHlr CsHaSOa CaHaSOr n-CsHlr n-CaHla CsHsSOs CsHsSO2 n-CeHia CZHK CsHa CsHs OCHa C B H ~ C H BCN C6HaCHa C N CON(CzHs)z CsHa COzC(CHa)a CsHs
LD
Conm..
M
He 0.4 Df .4 Df .4 Df .4 HC .4 Df .4 .4 Df .ig D< D k .12 .14 H' HI .23 H"' .12 H" .15
B -a-s Concn., Temp., Time, % % Net steric Solvent TYDe M OC. hr. Rac. Exch.8 course .. 4.5 62 93% Ret. 0,396 25 0.05 (CHa)sCOK (CHdrCODd 8.0 96 92%Ret. 25 0.70 (CHa)aCOK ,224 (CHa)aCOH 6 40 85% Ret. 25 0.80 .048 (CHa)rN +OH (CHdaCOH 2.2 69 97%Ret. 75 165 HOCHZCHIOK .5 HOCHZCHIOH DOCHzCHzODg DOCHzCHzOR .5 100 2.25 4.5 53 91%Ret. 100 HighRet. 48 7.0 .5 100 CHaOK CHaOH 98 90%Ret. 9.8 1.0 ,200 25 (CHa)&O-CHsOHh CHaOK 13 51% 1nv.i 20 140 260 ( H O C H ~ C H ~ O ) ~ H(HOCH~CH~O),K .36 4 Rac.orinv. 6.6 420 .40 260 (HOCHzCH2O)aK (HOCHzCHz0)aH 19 100% Rac. 1 . 3 20 ,013 25 (CHaIaCOK (CHdaCODd 52 100% Rac. 19 52 .14 84 DOCHzCHzONa DOCHzCHzODg 51 -100% Rac. 1.5 54 .17 70 (CHI)sCOK (CHs)aCOD 23 -100% Rac. 0.25 2 5 .0051 25 (CHdrCOK (CHdaCOD
-
M.p., 47.5-48.0" [ a I 2 % 1 8 -13.3" (c, 5.37, Optically pure unless otherwise specified. b Leaving group, H or D. CHC13). Analyzed by combustion and falling drop method t o be 99% 0-D. 6 Analyzed by combustion and falling ~ ~ ~ (C, 5.06, CHCl,), 97% C-D by combustion and falling drop method. drop method. f M.p. 47.5-48.0°,[ C I I S ~-14.0 92% (CH3)2SO, 8% CH3O.H by weight. 87% 0 Analyzed by combustion and falling drop method to be 99% (0-D)z. optically pure 81y0m-D, by infrared analysis (see ref. 1). j Corrected for lack of optical purity and incomplete deuteratm a*2~ +37.4" ( I , 1 dm., neat), almost optically of starting material. b 97% a-D, by combustion and falling drop method. pure. a 4 6118.Io ~ (l, 1 dm., neat). n C I * ~ D$35.6" (1, 1 dni., neat).
'
We have now found that the steric course of the reaction varies widely with the structure of the carbanion-stabilizing group attached to the seat of substitution. The steric course in each case was through Of the amount (1) D. J. Cram, C. A Kingsbury and B. Rickborn, THISJOURNAL, 81, 5835 (1959).
The second type of system, exemplified by 2 phenylbutane, probably forms a carbanion which is essentially flat, due to delocalization of charge (2) Hydrogen or deuterium are only two of a number of possible leaving groups in this general reaction [see D. J. Cram, A. Langemann, J. Allinger and K. R. Kopecky, {bid.. 81,5740 (1959)l and subsequent papers of the series.
