40
T. H. SIDDALL, 111, AND W. E. STEWART
Kinetics of Rotation around the Aryl-Nitrogen Bond in Some ortho-Substituted Acetanilides'
by T. H. Siddall, 111, and W. E. Stewart Savannah
River Laboratory, E . I . dzr Porlt de Nemours & Co., A i k e n , Soicth Carolina 29801 (Receiced M a y 2, 1968)
Kinetic quantities are reported for rotation around the aryl-nitrogen bond for eight ortho-substituted anilides of the tllie RiC(O)S(R?)(o-Rs)CsH5. The data are obtained by combiiiiiig measured reequilibration rates of separated diastereoisomers with pmr signal shape analyses; kinetic quantities cover a range of rates of up to lo6. Possible activated states are discussed,
Introduction There have now been a Iiuniber of studies of slow rotation around the aryl-nitrogen bond in anilides of the general
and a limited quantitative study with diortho-substituted anilidesS6 Only ref 3 and 4 have reported quantitative studies with anilides with single ortho substitution. Even in these two cases the kinetic data for the rotation were obtained solely by pmr signal shape analysis, and in one of these cases the analysis was approximate. Signal shape analysis can yield reliable results in the most sensitive region of intermediate exchange. However, over any extension, to the range of high and low exchange rates, signal shape analysis is subject to a variety of systematic errors.6 In other words, the free eriergy of activation, A F * , in the central part of the exchange region may be reliably determined, but the energy of activation, E,, and the frequency factor, Ao, may be much less certain. This paper reports results that reduce the likely errors in E , and Ao. This work is based on compounds of the general type above, except that R1 contains an asymmetric carbon atom. We were able to separate nine anilides of this type into substantially pure diastereoisomers (or epimers) as Crystalline solids. Reequilibration of the pure isomers was followed by the growth and decay of the appropriate pmr signal^.^^' I n this way rates were determined a t lower temperatures. For six of these compounds, rates could be obtained by signal shape analysis* a t higher temperature. (Only the central part of the exchange region was used.) By combining these two techniques, reequilibration and signal shape analysis, rate measurements were extended over a range of lo6 and a temperature range up The Journal of Physical Chemistry
to 150°.9 The range of these experiments permitted E , and log AOto be determined to within 57,.
Experimental Section The anilides (listed in Table I and Table IJ) were synthesized as previously described2 and were given initial purification by distillation under high vacuum. I n most cases, a pure crystalline isomer was easily obtained from such solvents as hexane, rnethylcyclohexane, or diethyl elher, or mixtures of one of these with methylene chloride or acetone. However, in no case did we isolate both epimers of the same compound. The isomer that was isolated is identified by its pmr signals (see Table 111). Compound V was obtained as a pure isomer only after long standing as a two-phase system with hexane a t about -5'. Compounds VI1 and IX were obtained as one epimer somewhat con-
Ix taminated by the other epimer and in poor yield only after standing for weeks in hexane solution at about (1) The information contained in this article was developed during the course of work under Contract AT(07-2)-1 with the U. S.Atomic Energy Commission. (2) (a) T. H. Siddall, 111, and C. A. I'rohaslca, J . Amel. Chem. Soc., 88, 1172 (1966); (b) T. H. Siddall, 111, J . O r g . Chem., 31, 3719 (1966). (3) B. J. Price, J. A. Eggleston, and I . 0. Sutherland, J . Chem. Soc., 922B (1967). (4) Y. Shvo, E. C. Taylor, IC llislow, and M. Itabm, J . Amw. Chem. Soc., 89, 4910 (1967). (5) T. H. Siddall, 111, Tetrahedron Lett., 4515 (1905). (ti) A. Allerhand, H. S. Gutowsky, J. Jonas, and I?. A . Meinzer, J . Amer. Chem. Soc., 8 8 , 3185 (1966).
(7) T. H. Siddall, 111, Inorg. S z t c 2 . Chcm. Lett., 1, 155 (1965). (8) T. Nalcagawa, Bull. Chem. Soc. Jap., 39, 1006 (1966). (9) Such a combination of techniques m a s first suggested by .-i. Mannschreclc (see A. Nannschreclc, 9.Mattheus, ;uid G. I~issm.ulr~, J . Mol. Spectiosc., 23, 15 (1967)).
KINETICSOF ROTATION AROUND THE ARYL-NITROGEN BOND
41
Table I : Kinetic Quantities Compd"
8,000
20.3
19.2
11.9
13 000
20.1
19.8
12.5
850
21.7
22.6
13.5
300
22.3
22.1
12.7
5 600
20.5
18.9
11.5
1,400
21.3
21.1
12.6
1.7
25.4
23.8
11.6
1.8
2.5.3
23.5
11.4
0
0
0
WI.
a A 100-mg sample of the compound plus 500 pl of CHC12CHClr. RI = CtjHj(C1)HC-, except R1* = CeHs(OC(O)CHZHC-. footnote a, Table 11.
-5'. Perhaps the rate-limiting step in the isolation of epimers of VI1 and IX involves asymmetric transformat h n and is the process of epimerization itself, which
See
would be very slow (IC < 10-7 sec-1) below 0" for these compounds. However, VIII, with similar epimerization rate, was obtained as a pure epimer in the same Volume 78, h'umber 1 January 1969
42
T. H. SIDDALL, 111, AITD W. E. STEWART
Table I1 : Equilibrium Results' Compd
I 11 I11 IV
v
VI VI I VI11 IXb
Table I11 : Detailed Rate D a t a
Equil constant ( K )
1.0 ( - l S 0 ) , 0.94 (O'), 0.95 (3'), 1.0 (80") 0.50 (l"), 0.66 (20'), 0.69 (SO'), 0.60 (90') 0.81 (7"), 0.81 (24')) 0.77 (30°), 0.90 (90') 1.8 (22'), 1.6 (SO'), 1.6 (80'), 1.7 (105') 1.0 ( - S O ) , 1.0 (5'), 1.1 (900) 1.0 (--5'j, 1.0 ( 5 O ) , 1.0 ( 2 5 O ) , 1.1 (80°), 1.1 (110') 1.4 (22'), 1.3 (60°), 1.3 (so'), 1.3 (144') 1.6 ( 2 2 O ) , 1.6 (60"), 1.6 (80") 2.0 (25'), 2.0 (80°), 1.7 (144")
a For o-methyl compounds, K is always the ratio of the area of the low-field methyl signal to the area of the high-field methyl signal. For I11 and IV, K 15 calculated from the ratio of the areas of high-field to low-field signal for the proton a t o the carbonyl group. For IX, K is the ratio of the low field to the high field for the a-proton iignal. For close examination of the spectra, we believe this is a consistent comparison of epimers. However, there is no proof of this. The rate data are calculated to be consistent with these assumptions. Values for IX are approximate signal overlap precludes accurate valiies.
Compd and comment 1. The methyl signal a t low-er field grows in.
11. The methyl signal a t higher field grows in,
111. The a-proton signal a t higher field grows in (proton a to carbonyl).
'
IV. The a-proton signal at lower field grows in.
V. The methyl signal a t lower field grows in.
X
XI
have given no crystalline products. I n times past,'O the process of "second-order" asymmetric transformation by crystallization has been of considerable interest. Some of the compounds in Table I may be particularly well suited to a study of this process by nmr spectroscopy. However, we have not explored this possibility. All experiments were performed in CHC12CHCL that had been passed through a column of Linde JIolecular Sieve shortly before use. This solvent was chosen because of its properties as a solvent, its stability, boiling point, and lack of signals a t high field. Samples for signal shape analysis or samples which mere kept for any length of time were scaled under vacuum. All measurements were made with a Varian A-60 spectrometer equipped with the V-6057 variable-temperature accessory. The methyl alcohol and ethylene glycol "thermometers" provided with this accessory were calibrated against a thermocouple. The manufacturer claims a control of 1 2 " ; our experience supporta this. This uncertainty of up to 2' is the controlling error in our experimental work. Almost always, a scatter of 2" is sufficient to account for the scatter of rates on Arrhenius plots of our data. It is this scatter that sets a typical variance of about 5% in determinaThe Journal of Physical Chemistry
k,
O C
sec -1
- 5" 4- 5" SOb 95b
~
way with comparative ease, though in unmeasured yield. Even after months of standing
Temp;
VI. The methyl signal a t lower field grows in.
VII. The methyl signal a t higher field grows in.
3 . 4 x 10-4 7 x 10-4 2.9 4.1
looc
5
122 131° 135c
17 34 47
- 14" 1" 13lC 136'
+
7 x 10-b 5 x 10-4 50 100
14asd 2ja 104b 10Bb
9 x 10-6 1 . 9 x 10-4 6X 2.9 3.2
logb
5
1llaId 120"Vd
3.7 6
23" 33" 42a 135b 14jb
3 . 2 x 10-4 5 x 10-4 1 . 9 x 10-3
7"
- j" +5" 90* 93b 10lb 132' 135' 137' 141" 150C
5 20 1.5 4.4 2.7 3.1
field grows in.
10-4
10-4
4.5 20 25 29 35 60
6 X Oa 1 . I x 10-3 22",e 8 X lom4 22"lf 22a'Q 8 X 9 x 10-4 22"'h 2.5 100' 3.5 llOb 4.4 114b 5.5 119' 25 131' 26 140' 36 144"
1 . 1 x 10-6 1.0 x 10-4 1 . 1 x 10-8
22" 60"
80"
VIII. The methyl signal a t higher
x x
1.2
22" 60" 80"
x
10-6
1.0x 10-4
9
x
10-4
From signal shape analysis of aa From reequilibration. proton signals. ' From signal shape analysis of methyl signals. 25 mg/500 Second set of experiments. ' 100 mg/500 pl. pl. 50 mg/5OO PI. 200 mg/ci00 pl.
'
KINETICS OF ROTATION AROUND THE ARYL-NITROGEN BOND
43
n # Rings
)c
Solvent
(21
= Solvent Side Band
Tetramethyl Silane
Figure 1. Pmr spectrum of
VI (100 mg and 500 p1. of CHClzCHClz a t 40”).
tions of E , and log A,,, as estimated from least-squares fits of data to Arrhenius plots. It is interesting to see so many reports in the literature to a much higher precision obtained with the same equipment, but with no indications that any unusual precautions have been taken or modifications made to ensure better temperature control. The signal shapes of rate constants were determined by manually matching the theoretical8 and experimental spectra. At least two of the matching parameters suggested by Nakagawa* were used for each match. We preferred manual matching to computer best fit niatching. The manual matching is a t least as rapid when a number of similar spectra are to be treated. Also as a matter of personal preference, we obtained a better “feel” with respect to obtaining good experimental spectra and malting the match to the theoretical spectra. Aside from the rate constant itself, three other physical parameters enter the signal shape equation. These are signal width a t half-signal-height in the absence of exchange (w),the chemical shift between sites in the absence of exchange, and the relative isomer (or site) population (see Table I1 for isomer ratios). We extrapolated these quantities into the region of intermediate exchange from their temperature dependence in the region of slow exchange. I n some cases w was slightly different for the two sites for the ring methyl protons (see Figure 1 where t u = 1.2 and 1.4 cps). I n
these cases, we took the average of the two values. The large chemical shift between ring methyl sites (typically 0.6-0.8 ppm) makes the error caused by this averaging inconsequential. The detailed techniques and calculations for obtaining rate data from reequilibration experiments have already been de~cribed.~.’
Results The kinetic quantities are summarized in Table 1. The kinetic resulls have all been computed for the equilibration with the low-field methyl signal and/or high-field signal from the proton a to the carbonyl group growing in. Table I1 is a compilation of equilibrium results. Table I11 gives the detailed kinetic data. Figure 1 gives the pmr spectrum of VI as an illustration tboassisl. in the discussion below. The o-methyl signals were used for monitoring the rates in the reequilibration experiments with I, 11, and V-VIII. For I, V, and VI, both the o-methyl signals and the signals from the proton a to the carbonyl group
were used in the signal shape analysis.
For 11, the
(10) For example, see the review by M.M.Harris, Progr. Stereochem., 2, 157 (1958).
Volume ‘73, Number 1
January 1969
44
T. H. SIDDALL, 111, AND W. E. STEWART
isomer observable by pmr spectroscopy. The trans a-proton signals were obscured by the solvent signal. For VI1 and VIII, the signals are not broadened enough isomer must exist at least 2 or 3 kcal in energy above the even a t the boiling point of the solvent, 146”, to allow cis isomer. signal shape analysis. The reequilibration rates for I11 There are four possible activated states for rotation and IV were monitored with the a (to carbonyl)-proton around the nitrogen-aryl bond (called simply the aryl signals as was the signal shape analysis. Compound IX bond below), of which A is to be preferred is not listed in the tables. Owing to overlap of signals, a quantitative study could not be made with this compound. However, it was possible to conclude qualitatively that, as expected, the barrier to rotation in I X is even greater than with VI1 and VIII. Although separate signals sets were generally observable from the K’ substituents of each epimer of a pair, signal overlap A B prevented their utility in rate studies. trans The standard concentration for the kinetic runs was RI R1 100 mg of the compound diluted with 500 ~l of CHC12I I CHC12. However, the concentration dependence was investigated with VI and found to be nil (see Figure 1). The work a t 25, 50, and 200 mg of VI with 500 pl of solvent was done a t the same time. The work a t 100 mg of VI was done several months earlier. The close C D agreement a t 25, 50, and 200 mg reflects the sort of precision obtainable when all the temperature controls are Of the two cis activated states, A must represent the set and left unchanged. more favorable passing position for steric reasons. A substituent other than hydrogen on the nitrogen Any substituents on Rz that are in the amide plane can atom of these anilides is apparently required for slow be rotated around the single bond to nitrogen out of the rotation to be detectable by pmr. None of the indicaamide plane to allow a conformation favorable to the tive signal multiplicity could be obtained for CsH5passing of R3 through that plane. A similar coopera(C1)CHC(0)SHCBH5 or C~Ha(Cl)CHC(O)SH(l-Clo- tive rotation that takes R1 out of the amide plane H 7 ) even with C6Hj(C1)CHC(0)NH-o,o’-(CH3)2C6H3requires rotation around the amide bond. Prom analnegative results were obtained a t -65” in CDC13. ogy with similar compounds,2b rotation around the It might be thought that rotation is rapid because of amide bond with its double-bond character must intunnelling by the proton on nitrogen. However, even volve not less than 10 ltcal. I n this sense, R3is “smalwhen this proton was replaced by deuterium, no eviler” than RIC(0)-. A similar argument selects C in dence of slow rotation could be obtained. preference to D, but not by so wide a margin because the oxygen atom is obviously smaller than R,. If the Discussion passing of R3 past Rz is the ultimate barrier to rotation Indications as to the Activated State. It is now well around the aryl bond, then A is to be preferred over C. establishedzb that the ground state for these molecules This follows plausibly because the cis isomer has a is thermodynamic preference of at least 2 kcal (though admittedly in the ground state). This analysis is obviously very much simplified and rests on the assumption that cross terms between primary consider a t’ions are negligible. It must be regarded as providing a working hypothesis rather than a firm choice between activated states. There are a number of considerations from Table I The benzene ring is out of the amide plane, that is, the that are consistent with the choice of A as the activated plane defined by the amide group state. The difference in rotational barrier between I 0 and V is almost within experimental error, and the difference between I and VI is only about 1 kcal. The C benzyl and the methyl groups are almost if not the same “size,” and the ethyl group is only LZ little larger. N< This could be the case equally whether the passiiig interaction were R1-123 or pLz-R3, provided RL can be roRotational isomerism is possible around the carbonyltated to a minimum size. However, the large incrense nitrogen (amide) bond. However, the isomer as in barrier with VI1 and VI11 suggests that ItL-&is the shown above with the RZgroup cis to oxygen is the only
/I
’\
The Journal of Physical Chemistry
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