not nearly so critical for formation of the amine complex as for that of the aromatic hydrocarbon. It is conceivable that the amino group of $-toluidine rather than the entire r-electron cloud of the aromatic nucleus may serve effectively as a center of donor activity. A much less intimate ‘arrangement of the complex components may, therefore, be required than when hexamethylbenzene is the donor. I t has been s u g g e ~ t e d ~ 6that 1 ~ ~2 : l and 1:2, as well as 1: 1 complexes, may form to some extent in solutions of aromatic amines and polynitrobenz e n e ~ . Although ~~ this matter was not thoroughly investigated in the present series of measurements on the $-toluidine complexes, there was no positive evidence for the formation of other than 1 :1 type (33) S. D. Ross and M. Labes, THISJOURNAL, 79, 76 (1957) ( 3 4 See, however, R. Foster and D. L1. Hammick, J . Chem. Soc., 2685 (1954).
[CONTRIBUTION FROY THE
DEPARTMENT O F CHEMISTRY
aggregates. I n the spectrophotometric studies of both the bipicryl and 1,3,5-trinitrobenzene complexes the $-toluidine concentrations were varied from 0.1-0.8 111 (the acceptor concentrations were of the order of M ) . When the resultant data were interpreted graphically according to equation 1, very satisfactory linear plots were obtained. I t is interesting to observe that the low donor strength of hexaethylbenzene as compared to that of hexamethylbenzene is again manifested when 1,3,5-trinitrobenzene is the donor. The spectrum of the nitro compound in chloroform is so little enhanced by hexaethylbenzene that it is questionable whether any significant donor-acceptor interactioii s occur in solutions of the two substances. Acknowledgment.-The authors are indebted to the National Science Foundation for a grant i n support of this research. DAVIS,CALIFORXIA
A N D CIIEMICAL
ENGIXEERIVG, u SIVERSITY
O F CAI,IFORNIA]
Kinetic Isotope Effects in the Acetolyses of Deuterated Cyclopentyl Tosylates’,2 BY A. STREITWIESER, JR., R. H.
JAGOW,
R. C. FAHEY ASD S. SUZCKI
RECEIVED OCTOBER28, 1957 The acetolysis rates of the tosylates of cyclopentanol, cyclopentanol-1-&cis- and trans-cyclopentanol-2-d and cyclopentano1-2,2,5,5-& are described. All of the deuterated compounds solvolyze significantly more slowly than does cyclopentyl tosylate itself. An analysis of the m-deuterium case based on statistical mechanics indicates that the isotope effect is due predominantly t o the change of a tetrahedral C-H bending vibration t o an “out-of-plane’’ deformation in the transition state. The &deuterium isotope effect is ascribed to the change of a tetrahedral C-H bending mode to a vibration in the transition state along a molecular orbital resulting from increased hyperconjugation in the electron deficient system. An argument is advanced for discounting any important specific solvation of the p-hydrogens in the solvolyzing molecule.
The isotope effect in solvolytic reactions derived from the substitution of p-hydrogens by deuterium in a substrate molecule was first exploited by Shiner3 and by Lewis4and was demonstrated by them to be a valuable new tool in understanding such reactions.b I n the present work, we wished to determine the isotope effect derived from an a-deuterium atom and the effect of stereochemical configuration of a /?-deuterium, independent of conformational differences. For these purposes, we prepared the tosylates of cyclopentanol-1-d (I), cisand trans-cyclopentanol-2-d (czs-I1 and trans-11, respectively) and of cyclopentanol-2,2,5,5-d4(111) and determined the solvolysis rates in acetic acid. Preparation of Deuterated Cyclopentano1s.-The opening of epoxide rings with lithium aluminum hydride has been amply demonstrated to be a completely trans opening.6 Consequently, the (1) T h i s work was communicated in p a r t by A. Streitwieser, Jr., Jagow and S. Suzuki, THISJOURNAL, 77, 6713 (19551, and b y A. Streitwieser, Jr., a n d R. C . Fahey, Chemisfry 6’ Industry, 1417
R. H.
(1957).
(2) This research was supported in part by a grant from t h e Petroleum Research F u n d of t h e American Chemical Society. (3) (a) V. J. Shiner, Jr.. THISJOURNAL, 75, 2925 (1953); (b) 76, 1603 (1954). (4) E. S. Lewis and C. E. Boozer, ibid., 76, 791 (1954). (5) For reviews see (a) K. B. Wiberg, Chcm. Reus., 6 6 , 713 (1955), and (b) A. Streitwieser, Jr., ibid., 56, 571 (1956). ( 6 ) For example, see P. A. Plattner, H. Heuser and M . Feurer, H d v . chim. Acta, 32, 587 (1949); L. W. Trrvoy and W. G. Brown, THISJOURNAL, 71, 1675 (1949); W. G. Dauben, R . C. Tweit and R. L. McLean, ibid., 7 7 , 48 (1955).
structure trans-cyclopentanol-2-d was confidently assigned to the alcohol obtained in good yield from the reaction of cyclopentene oxide with lithium aluminum deuteride. The density of the alcohol indicated 1.O deuterium/molecule. This material was converted in the usual way to the tosylate (trans-11-OTs) which was treated with tetramethylammonium acetate in pure, dry acetone solution. The product, obtained in 76y0yield, was assigned the structure of cis-cyclopentyl-2-d acetate (czs11-OAc) since the reaction conditions were chosen to favor an Sx2 reaction. Hydrolysis gave cis-11. The infrared spectra in the 4-11 p region of czsand trans-I1 and of the corresponding acetates are compared in Table I. The spectra show a number of differences, particularly in the 9-11 ,u region. The cis and trans compounds are not only clearly different and distinguishable, but are not mutually contaminated to any observable extent. Cyclopentanone-2,2,5,5-d4 (IV-d4) was prepared by repeated exchanges of cyclopentanone (IV) with weakly basic D20. The infrared spectra of the two ketones showed interesting features. In IV-d4, the C-D stretching doublet a t 8135 and 2230 cm.-l was much less intense than the C-H doublet in IV a t 2880 and 2965 cm.-l which is little changed in IV-d4. Clearly, the intensities of the CY-C-H stretching modes are much less than those of the P-C-H, in agreement with Francis7 that a carbonyl (7) S A Francis, J. Cbeni
I’iivr
~
19, ( I ? (1951).
2327
ACETOLYSESOF DEUTERATED CYCLOPENTYI, TOSYLATES
May 5 , 1058
TABLE I INFRARED SPECTRA Wave length of absorption bands in microns" Cyclopentyl tro7lS-11 cis-I1 111 acetate
Cyclopentanol
I
3.0b 3.39 3.48sh
3.0b 3.37 3.48 4.63sh 4.69 6.88b
3.0b 3.39 3.49 4.62
3.0b 3.39 3.49 4.56
6.87b
6.88b
7.58
7-47 7.66 8.63 9.11 9.47 9.69
7.48 7.69 8.61 8.98 9.30 9.64
7.51 7.72 8.85 9.3b
10.10
9.92 10.56
9.98 10.24
6.87 6.96 7.46 7.66 8.55 9.35 9.67 10.07 10.72
8.38 8.97 9.12 9.64
9.86 10.54 10.87 11.29w
3.0b 3.39 3.49 4.49 4.72 6.9b
3.37 3.50 5.77 6.945 7.285 7.385 8.00 8.57 9.5sh 9.795 10.28 11.12 11.93~
tram-I1 acetate
cis-I1 acetate
3.37 3.50 4.58~ 5.77 6,945 7.285 7.36sh 8.0 8.61 9.10 9.55sh 9.8b 10.30 10.94 11.12 11.71
3.37 3.50 4.54~ 5.77 6,945 7.286 7.36sh 8.0 8.63 8.91 9.55 9.78 10.43 10.62 11.12 12.02
11.21 11.23 11.37 11.68 11.91 12.4b 12.57 12.56 12.45 Spectra were taken on liquid films with a Baird AB2 infrared spectrometer using sodium chloride optics; b means broad; sh indicates shoulder and w means weak. 11.19 11.96
group greatly decreases the intensities of a-C-H stretching bands. A doublet at 1457 and 1474 cm.-' in I V is unchanged in intensity or position in IV-db and is assigned to the @-methylene deformation. In hydrocarbons, a methylene deforA mation usually occurs a t about 1465 more intense band a t 1409 cm.-' in IV has vanished in IV-dd and is assigned to a-methylene deformation. Francis' and Jones, et U L . , ~ assign 14101415 cm.-l to a methylene group alpha to a ketonic carbonyl group. The band near 1360 cm.-', attributed by both sets of authors to the same structural feature, is not present in cyclopentanone. Reduction of IV-da with lithium aluminum hydride a t -80" gave a good yield of I11 having 4.1 f 0.1 deuterium atoms per molecule (by density). Some comment on this reduction is necessitated by the report of Brownlo that the reaction of cyclopentanone with lithium aluminum hydride gives initially an insoluble complex and that refluxing in ether" or preferably tetrahydrofuranlo is required to give a good yield. We find that the reduction proceeds smoothly at Dry Ice temperature with no evidence of complex formation and with no apparent loss of deuterium. Probably a t room temperature a significant amount of the enolate salt is formed which requires more vigorous treatment for reduction. At low temperatures, however, enolate salt formation is clearly not important. Correspondingly, cyclopentanone is reduced a t -SOo with lithium aluminum deuteride to yield an alcohol having 1.0 i 0.1 deuterium atom per (8) S. A. Francis, J . Chem. Phys., 18, 861 (1950). (9) R . N. Jones, A. R. 11. Cole and B. Nolin, THIS JOURNAL, 74, 5662 (1952). (10) W. G. Brown, "Organic Reactions," Vol. V I , John Wiley and Sons, Inc., New York, N. Y., 1961, p. 475. (11) J. D. Roberts and C. W. Sauer, THIS JOURNAL, '71, 3028
(lYlY).
molecule (density) and which is not &I1 or trunsI1 (compare infrared spectra in Table I ) ; the structure of cyclopentanol-1-d (I) is assigned. The tosylates of each of the cyclopentanols were prepared in the usual way with tosyl chloride in pyridine.
Results and Discussion The kinetics of the solvolyses of solutions of the tosylates in dry acetic acid containing roughly equivalent amounts of sodium acetate were determined a t 50". Each determination was run at least in duplicate. The reproducibility was generally about 1%. The rate constants measured are listed in Table 11. TABLE I1 ACETOLYSES OF DEUTERATED CYCLOPENTYL TOSYLATES AT 50.0" Alkyl tosylate
[ROTS] [NaOAc]
106k, sec-1
kH/kD
AAF f per deuterium, cal./ mole
0.1017 0.1170 4.19 1.00 .. ,1170 4.26 .0955 .1221 3.78b 1.15 90 Cyclopen.0313 .1221 3 . 6 6 tyl-1-d .Os91 .0918 .1221 3.70 trans-Cyclo.0948 .lliO 3.65 1.16 110 .1170 3.63 pentyl-2-d .0884 1.22 127 .1170 3.50 cis-Cyclo.0965 .1170 3 . 4 3 pentyl-2-d .Oi36 .1170 2.06 2.06 116 Cyclopentyl,0935 .1170 2 . 0 5 2,2,5,5-d4 .0900 KOAc = 0.113 At, a Previous results: 4.28 X lO+sec.-', (J. D. Roberts and V. C. Chambers, THIS JOURNAL, 73, 5034 (1951)); 3.84 X 10-6 set.-'. no acetate ion added (S. Winstein, B. K. Morse, E. Grunwald, H. W. Jones, J. Corse, D. Trifan and H. Marshall, ibid., 74, 1127 (1952)); sec.-l, no acetate ion added (H. C. Brown and 3.82 X G. Ham, ibid., 78, 2735 (1956)). * A t 50.1'. Extrapolates to 3.72 x 10-6 sec.-I at 50.0". Cyclopentyl'
In all cases, the deuterated compounds solvolyze significantly more slowdy than does cyclopentyl tosylate itself. cr-Deuterium Effect.-Electronic wave functions are virtually identical for isotopically substituted molecules.12 Hence, in the absence of any significant change in the average electron distribution due to anharmonicity ( o d e infra),the source of deuterium isotope effects must be sought almost wholly in the rotational and vibrational partition functions. Froin absolute rate theory and statistical mechanics, assuming only the usual approxiina t'ions that the partition function is the product of translational, vibrational and rotational, etc., partition functions and the neglect of anharmonicity, Bigeleiseni3has derived an equation for the isotope effect on rate which is given as equation 1 in a rearranged form applicable to the present discussion. UII
tant way'j; hence, invst of the fundamental frequencies will hardly be altered by the deuterium substitution. For these frequeiicies, the ratios, U H / U I , and (1- e (1 - e - U D ) will be unity. The vibrations most affected by t!ie change from cyclopentyl tosylate to cyclopentyl-1-d tosylate will be the stretching and bending frequencies of the tertiary C-H bond. Since these frequencies are greater that; 1000 em.-', a t temperatures near room temperature, e-" g 0; thus all of the (1 -e -") ternis cancel. For such frequencies also, equation 21fi is generally a good api"o"imatiot1.
-
Substitution df 1111 by tlie use of eqtution 2 reduces equation I to equation 3, in which the product is taken over ilic three tertiary C-H stretching arid bending fundamentals In equation 3 only the effects due to changes in zero-point energy remain from the origiiial equation 1. In tlie related system of substitution on n bei;Lelie ring, Melander'* concluded that Lero-point energy effects were dominant. Insertion of the values for the universal constants gives equation 4 or, equivalently, 5.
In this equation, K is the transmission coefficient, m;t is the effective mass for the reaction coordinate, u is the symmetry number, ui = hvi/kT, the product being taken over all of the fundarnental frequencies, with repetition of degenerate frequencies. Subscripts H and D refer to the hydrogen and deuterium compounds, respectively. The ratio of the transmission coefficients may be taken as unity. Because of the relatively small contribution to the effective mass of the hydrogen being substituted b y deuterium, the mass term may also be taken as close to unity.14 The symmetry numbers are the same in the ground state and the transition state in this case, hence the symmetry number term is also unity. Deuterium substitution will change sipitificantly only those vibration frequencies which involve the vibration of the substituted hydrogen in a11 impor(12) Cf.( : I ) G. Herzberg, "Molecular Spectra and ,2101cculcir Structure," Vol. I , I). Van Nostrand Co., Inc., New T o r k , S . Y . , l ! l i O , 1). 1 6 2 ; ( b ) Val. 11, p. 227. (13) J. Bigeleisen, J . Cheiri. P h y s . , 17, 675 (1949). (14) T h e argument suggested by Professor Kenneth S . Pitzrr is as follows: Superimposed on t h e complicated motions and vibrations of all of t h e constituent atoms of t h e reacting system are t h e relatively more simple motions which comprise t h e reaction coordinate; m is t h e effective mass along t h e reaction coordinate required t o express the kinetic euergy along this coordinate and is generally a complicated function o f t h e system. Important motions in t h e reaction of cyclopentyl tosylate are t h e stretching of t h e C-X (X = OTs) bond and t h e forward movement of t h e a-I3 from a tetrahedral to a more trigonal position. T h e mass of the hydrogen is so small compared f n that of thc other moving atoms t h a t its Contribution t o thi3 kinetic rnrrgy is sniall; hence, to our approximation, rcpl:iccincnt 1,y d r i i teriiitn would be esperted t o make a negligible change ill ?ti 5;. Some idea of t h e magnitude of this term m a y lie obtained by regarding t h e C-D group as acting as a unit; i.e., a s if t h e C" was coliverted t o C'S. An isotope effect of about 4 % is found fur the decarboxylation of malouic acid containing CIa (P, E. Yankrvich and €1. S. Weber, THISJOURNAL, 77, 4513 (1955)) only part of which is attributable t o t h e effective mass term. We might reasonably expect. then t h a t this term n i r i 1 1 , l aniniint t o onlv a ft.m 1x.r rrnt. w i t h our 4)
11.111
(4)
'There is no problem in assigning reasonably good values to the tertiary C-H frequencies: 2890 cm.-l for C.-H stretching and about 1340 c ~ i i . -19~ for the two approximately degenerate bending vibrations. The problem arises in assigning frequencies to the three fundamental vibrations in the transition state. I n the cyclopentyl cation, the fundamentals may be approximated as C-H stretching, in-plane bending and out-of-plane bending modes. As a model for a C--H bond attached to a carbonium ion, we have used an ,aldehyde C-H; the carbor, atom involved in both cases is sp2 hybridized, slid the carbonyl carbon m a y be expected to have a t least some net positive charge (however, d e inj".) The assignnieiits for such a bond may be taken as -2800 em.-' (stretching),'O 1350 c m - ] (in-plane bending) 21 and -800 cm-' (out-of-plane bending.)2 1 , ? 2 The changes may be represented 1151 Reference 1211, p. 2 2 8 . 110) In t h e harmonic oscillator approximation, the group t o which thr hydrogen (or deuterium) is attached is relatively so large t h a t it ni:i!.es h u t a nezligihle contribution t o the reduced ma55 of the bond iinlinite rna:>s approximation) :in11 t h e riitio, v i i / v o , should equal t ' ? Jiccaiiw t l i r a t t a c h e d m a s s is not infinite and perhaps :tlso because of i~nliarmonicity,t h e ratio i, iictudliy sorriervhat imirlier and i,, c i n i ~ ; i l l y:,l:niit 1 3,; ( ~ C Ctlir ni.rny < , Y ~ I T I ~ I Ii.n- rei 1 2 h J . 'L of other iiii~il.rniPnt~iic >Iiniild n i j t lie ~lcriiiii~ i b sm:ill. :inti 111;111y ri.calliniic?r, I l c l a . C h i m Acta, 38, 1597, 1617 (1955). (4.5) A . Mcl.eau a n d R . Adams, T t r r s J O U R N A L , 68, 804 (1936).
233 1
'rABLB
111
A C E T O L Y S I S O F Cis-CYCLOPEXTYL-2-d
TOSYLA~E
'knip. 50.0'; [ROTS] = 0.0965; [NaO.lc] = 0.1170; calcd. infiiiity titer, 1.762 i d . ; found, 1.779 ml. Time, min.
Titer, ml.
0 108 9 209.2 315.3 384.5 488.0 555.8 G16.7
7.609 6.066 4.858 3.920 3.393 c>
-.,LaI
I .
2.356 2.082
lOSk, sec. -la
3.46 3.55 3.50 3.50 2.32 3.52 3.50 __ 8 . 5 1 =k 0 ,02'
Using equation for a first-ordei- rcaction. squares k = 3.502 X sec.-l.
The least
per 1nolecule).~5 The tosylate iras prepared as above, m.p. 28-29'.
Cyclopentanol-1-d.-Cyclopentanone was reduced with lithium aluminum deuteride using the procedure detailed above for the reduction of IV-dr; yield 3 g. (37%) of alcohol, b.p. 140.5-141.5", dZ50.9547 (corresponding to 1.07 deuterium atoms per m ~ l e c u l e ) . ' ~The tosylatc prepared as above had m.p. 25.5-26".
Kinetics.--Anhydrous acetic acid WdS prepared by treating reagent grade acetic acid, which had been analyzed for water b y the Karl Fischer method, with a n amount of acetic anhydride calculated to give a lY0 excess. Freshly fused sodium acetate and dried p-toluenesulfonic acid were used t u make up stock solutions in acetic acid. I n most of the runs about 2 g. of the tosylate was dissolved in sodium acctate stock solution in a calibrated 100-ml. volumetric flask. The flask was placed in a thermostat at 50.00 i 0.05' and aliquots were removed periodically with a calibrated 5-1d. automatic pipet and titrated potentiometrically with stock p-toluenesulfonic acid solution iu acetic acid. The procedure for the cyclopentyl-1-d tosylate runs was similar except that the solution was placed in sealed tubes which were periodically withdrawn and titrated. Infinity titers generally agreed with the calculated titers ivithin 1-270. A typical run is shown in Table 111; a suinniary of rate constants calculated by the method of least squares is presented Table 11.
Acknowledgment.-%'e are indebted to Professors W. D. Gwinn, I(. S . Pitzer, H. S . Johnston, G. C. Pimentel and W. E. Doering for discussions and suggestions which greatly assisted the formulation of some of the concepts and arguments presented in this paper. We thank Professor William H. Saunders, Jr., for exchange of information in advance of publication. BERKELEY 4, CALIF.
[ C O N T R I B U T I O N FROM THE DEPARTMENT OF CHEMISTRY, UNIVERSITY O F S O U T H E R N C A L I F O R S I A ]
Heterocyclic Compounds. VI.
Reduction of 3-(3,4-Methylenedioxyphenyl)-4-nitro1-phenyl- 1-butanonel
BY MILTON C . KLOETZEL AND
JACK
L. PIXKUS
RECEIVED NOVEMBER 11, 1957 Reduction of 3-(3,4-xnetl~ylenedioxyphenyl)-4-nitro-l-phe1~yl-l-butanone (I) by catalytic hydrogciiation 01 cr platitiurll black or Raney nickel, or by zinc dust and aqueous ammonium chloride, yields 4 - ( 3 , 4 - m e t h y l e i i e d i o x y p h e n y l ) - 2 - p l ~ e 1 ~ ~ ~ - ~ ' pyrroline (VI). Chemical and physical evidence clearly supports a A*-pyrroline structure for 1'1.
Pyrrolidines and Ai-pyrrolines have become increasingly recognized as characteristic reduction products from aliphatic y-nitro However, despite the fact that aromatic nitroketones frequently have been reduced t o N-oxygenated derivatives of indole or quinoline, l 2 oxygen-containing reduction products from aliphatic y-nitro ketones have remained elusive. Kohler and Drake2 reported the only products from catalytic hydrogenation of 3- (3,4-methylenedioxyphenyl) -4-nitro-1-phenyl-1-butanone (I) over platinum black, to be amino ketone IT, pyrrolidine I11 and an hydroxylated pyrroline to which (1) Partially abstracted from a portion of the P h . D dissertation of Jack L. Pinkus. (2) E. P. Kohler a n d N . I.. Drake, 1'HrS J O L J K N A I . , 45, 9144 ( 1 9 2 3 ) . ( 3 ) A . Sonn, B e y . , 68, 148 (1035); 72, 2150 (1039). (1) J . Dhont and J. P. Wibaut, Kcc. Lyav. chiwt., 63,81 ( l < I W ) . ( 5 ) X I . C. Kloctzel, T H I S JouRNnr., 69, 2271 (1947). ( 0 ) P. h l . Maginnity and J. B. Cloke, ibid., 73,49 ( l 9 . j l l . ( 7 ) P. G. Bordwell a n d M. Knell, i b i d . , 73, 2354 (1951). ( 8 ) I,. I . Smith and E. R . Rogier. ibid., 73, 3837 (1931). (9) B. Witkop, ibid , 76, 5597 (1954). (10) X I . L. Stein a n d A. Burger, i b i d . , 7 9 , 154 (1957). (11) 14. C. Kloetzel, J. L. Pinkus and R. M. Mashburn, ibid., 79, 4222 (1957). (12) A . Reissert, Bev., 30, 1030 (1897); S. Gabriel and W. Gerhard, i b i d . , 64, 1007 (1921); l i . I , McCluskey, THISJ O U R K A I . , 4 4 , 3873 ( 1 9 2 2 ) ; S. (:&hiel and K Wu , 2445 ( l 9 2 : j ) I Mcisetilieimcr u u d I < , S l u l z , i b i c i . , 68, ~
they ascribed structure IV or V. Prior to our reduction studiesi3 this was the only instance in which an oxygenated pyrrole nucleus had been obtained by reduction of an aliphatic y-nitro ketone.I5 For this reason it appeared of interest to include nitro ketone I in a series of nitro ketones whose behavior upon reduction we have been studying. In our hands, reduction of I by hydrogen over platinum black or Raney nickel, or by zinc dust and aqueous ammonium chloride, yielded only 4-(3,4methylenedioxyphenyl) - 2 - phenyl - AI - pyrroline (VI). We obtained none of the products (11-V) reported by Kohler and Drake.2 Pyrroline V I was characterized by forination of a crystalline picrate, hydrochloridei6 and oxalatc. (13) Stein and Burgerlo recently reported the preporativn o f i i n oxyKen-containing base by reduction of an nliphatic nitro ketone b u t did not ascribe t o i t 0 structui-e. Sliortly thereafter, Brown, Clark and Todd" reported the syuthesis of two :dicyclic nitrones Ihy reductivc
