In the Laboratory
Rotational Barriers in Push–Pull Ethylenes: An Advanced Physical-Organic Project Including 2D EXSY and Computational Chemistry Tammy J. Dwyer and Julia E. Norman Department of Chemistry, University of San Diego, 5998 Alcala Park, San Diego CA 92110 Paul G. Jasien Department of Chemistry, California State University, San Marcos, San Marcos CA 92096
Students of organic chemistry are taught that rotations about carbon–carbon double bonds are not allowed and we attribute the high thermodynamic barrier to the stable p-π– p-π bond. Indeed, in ethylene the barrier to C=C rotation is approximately 65 kcal mol᎑1. This barrier can be significantly decreased, however, by positioning one or more electrondonating groups (typically amino groups) at one end of the C=C bond and one or more electron-accepting groups (–NO2, –CN, etc.) at the other. A molecule with such an arrangement of groups is referred to as a “push–pull” ethylene. The diminution of the C=C rotational barrier in push–pull ethylenes is a consequence of electronic/resonance effects, steric interactions between the donor and acceptor groups,
or a combination of both of these. In addition, delocalization of the amino nitrogen lone pair into the C=C π system results in an increased barrier to rotation about C–N bond(s) adjacent to the C=C bond, similar to that observed in amides. The dynamic processes occurring in push–pull ethylenes are well-suited to study by variable temperature NMR spectroscopy. Previous investigations by one-dimensional lineshape analysis (1, 2) have yielded C=C barriers of 10–25 kcal mol᎑1 and C–N barriers of 8–17 kcal mol᎑1 for a variety of substituted compounds. The low C=C barriers and high C–N barriers have been explained in terms of the capacity of the donor and acceptor groups to stabilize the developing dipolar transition state structures (for example, Equation 1). Continued on page 1636
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In the Laboratory
Two-dimensional exchange spectroscopy (2D EXSY) is a powerful technique for measuring both quantitative kinetic data (i.e., rate constants) and for providing mechanistic insights into dynamic processes. As an example of both applications, we have used 2D EXSY to study C=C and C–N rotations in a simple push–pull ethylene, methyl 3-dimethylamino-2-cyanocrotonate (MDACC, 1). The kinetic processes occurring in MDACC are diagrammed in Scheme I.
levels, depending on the degree of sophistication in NMR and computational techniques of the student and instructor. The entire work may be integrated as a multiweek project into an upper-division laboratory, or individual parts may be performed in small groups. This experiment complements a number of combined computer modeling–laboratory projects that have been reported in this Journal (3–6 ). Procedures
H
H
H
+
N
H
‡
H
N
H
H
C
C
C
-
NC
CH3 CH3
C C
CH3
C
CH3
CH3
NC
O
1
2
D CH3
B CH3 E
CH3 F
N H3C
O
C
O
NC
O C
N
H3C
C
C
(1) CN
CN
CH3 N
H
C
NC
CN
H3C
N
C
C
NC
H
C C
kZE OCH3
NC
N
H3C
kEZ
C
A CH3
C OCH3
NC
O
O
E
Z ? kZ'Z kZZ'
kE'E kEE'
C CH3 D H3C
E H3C
F CH3
N
kE'Z'
C
OCH3
NC
N C
kZ'E'
C
A CH3
CH3
B
C OCH3
NC
O
O
E'
Z' Scheme I
In Scheme I, the letters A–F refer to the unique magnetic environments of the methyl groups involved in the exchange processes. The rate constants kEZ and kZE (as well as k E′Z′ and kZ′E′) refer to the rotation about the C=C bond in MDACC, whereas kE′E, (or kEE′) and kZZ′ (or kZ′Z) correspond to the rotation about the C–N bond in the E and Z isomers, respectively. In the course of this experiment, students will perform a simple synthesis and purification, acquire a 1D variable temperature series of NMR spectra, collect and analyze low-temperature 2D EXSY data, and compute rotational barriers using quantum mechanical (QM) computational methods. This experiment can be performed at a variety of 1636
Preparation of MDACC MDACC was prepared according to a procedure given by Shvo and Shanan-Atidi (1b). All reagents were purchased from Aldrich and used without further purification. Methylcyanoacetate (1 mL; 0.011 mol) and N,N-dimethylacetamide dimethyl acetal (1.5 mL; 0.011 mol) were mixed at room temperature and allowed to stir for 30 minutes. Vacuum distillation (10᎑3 torr, 115 °C) of the yellow-orange liquid yielded a pale-yellow distillate that crystallized when cool. The solid was then recrystallized from methylene chloride–hexane in 80% yield with a melting point of 59 °C. NMR Spectroscopy The 1D variable temperature and 2D EXSY spectra were acquired on either a Varian UNITY-300 or Bruker ARX-300 spectrometer. Samples were prepared by dissolving 2.5–4.0 mg of MDACC in 700 µL of deuterated solvent (CDCl3, CD2Cl2, or CD3C(O)CD3). All 2D EXSY data were acquired at 300 MHz using a NOESY sequence with the States et al. (7 ) phase-cycling method to generate pure-absorption phase spectra. The spectra were collected with 1024 points in t2 using a spectral width of 1500–3000 Hz and mixing times of 50–400 ms. Typically 256 t1 experiments were recorded and zero-filled to 1 K. For each t1 value, 8 scans were signalaveraged using a recycle delay of 4 s. Computation The computational portion of this experiment can be carried out at a variety of levels that depend on the pedagogical goals and the software and hardware available. The use of QM methods is essential because molecular mechanics force fields are not accurately parameterized to handle the dipolar push–pull ethylenic systems. Even among QM techniques, semiempirical methods have difficulty in accurately describing the electronic structures of these systems and can yield unreliable estimates of the rotational barriers (8). The goal of the computational portion of this experiment is not to achieve quantitative agreement with experiment, but to establish a basis for interpreting trends in structure and corroborating the qualitative changes in rotational barriers. To achieve the stated goals of this experiment the simplest level of theory can be used. In some cases, the QM wave function used may not be the most appropriate from a theoretical perspective, particularly in calculating the rotational barriers in the non-push–pull system (but not the push–pull compounds), where a multiconfigurational wave function is needed to accurately describe the breaking of the π-bond. However, reasonable estimates of the energy barrier for rotation may be obtained from a single-configuration restricted Hartree–Fock (RHF) self-consistent field wave function. Calculations including electron correlation can be performed if desired with a concomitant increase in quantitative agree-
Journal of Chemical Education • Vol. 75 No. 12 December 1998 • JChemEd.chem.wisc.edu
In the Laboratory
ment with experiment, but once again are not necessary to show the major qualitative differences. Commercially available QM software such as Gaussian 94 (9) and SPARTAN (10) are suitable for these studies, as are other programs with the ability to locate minimum energy and transition-state (TS) structures. It must be noted, however, that if TS structures are being sought with more computationally intensive ab initio methods, it is imperative that an efficient saddle-point optimizer is available. In addition, for ab initio searches it is advisable to calculate analytical second derivatives. Pedagogically, there are three levels at which the computations in this experiment can be performed. These are listed below in order of increasing complexity. (a)
Optimize the structures of the minimum-energy E and Z isomers of MDACC and the non-push–pull analog 3-cyano-2-dimethylamino-2-methyl crotonate (CDMC, 2). From the optimized structures, analyze the trends in bond lengths and angles, compare electric dipole moments and/or partial charges on the atoms, and, if available, electrostatic potential maps. The relative stabilities of the E and Z forms of each compound can also be compared.
(b)
In addition to (a), locate the TS for the C=C rotation in each molecule and calculate the rotational barriers in 1 and 2. Compare the C=C barrier heights and the structural changes and charge distribution changes in the TS vs the E and Z minima in MDACC.
The data in Figure 1 are used to make qualitative observations on the relative magnitudes of the C–N rotational barriers in the E and Z isomers. Since the two N-methyl peaks of the E isomer appear to be broader at ᎑40 °C than those of the Z isomer, one may conclude that the C–N barrier in the E isomer is slightly lower than in the Z form. This makes sense, since the trigonal carbomethoxy group has larger steric requirements than the linear nitrile. At this point, the student can make a judgment as to the best temperature to run the 2D EXSY spectrum. Clearly, in order to see the maximum number of well-resolved crosspeaks, it is desirable to have the peaks well separated (i.e., lower temperature); however, in the limit of low temperature the rotational rates slow dramatically and cross-peaks will not be observed.
(c) In addition to (a) and (b), it is also possible to locate the TS for C–N and C–C(O)OCH3 rotations in 1 and 2. (Location of the C–N transition state can be quite difficult in these systems owing to the low C–N barrier and the similarity in structure to the nitrogen inversion saddle point.) These barrier heights and structural changes can be compared in the compounds as appropriate.
Results and Discussion
Variable Temperature Spectra The variable-temperature 1D 1H-NMR spectra of MDACC in CDCl3 are shown in Figure 1. At 25 °C (bottom trace, Fig. 1) the spectrum shows three sets of peaks in the region 2.0–4.0 ppm. The signal at 3.68 ppm corresponds to the –OCH3 protons of the carbomethoxy group. The peaks at 3.1 and 3.3 ppm arise from the –N(CH3)2 protons in the E and Z isomers, respectively, and they are broad because the C–N rotational rate is intermediate on the NMR time scale. The broad peaks at 2.35 and 2.45 ppm correspond to the C–CH3 protons in the E and Z isomers, respectively, when the C=C rotational rate is intermediate on the NMR time scale. As the temperature is decreased, both the C=C and C–N rotational rates slow and the –N(CH3)2 and C–CH3 signals sharpen and become better resolved. The –OCH3 signal also splits into two peaks owing to a slowing of the C–C(O) bond rotation at lower temperature. Focusing on the –N(CH3)2 and C–CH3 signals and referring to Scheme I, we see that when the C=C and C–N rotations are “frozen out”, a total of four N-methyl peaks and two C-methyl peaks are distinguished. These correspond to the four sites accessible for each N-methyl group as the rotamers are interconverted via rotation about both the C–N and C=C bonds and the two sites available for each C-methyl group as the E and Z forms (or E′ and Z′) are interconverted by C=C rotation.
Figure 1. Variable-temperature 1D 1H-NMR spectra of MDACC in CDCl3.
Figure 2. 2D EXSY spectrum of MDACC in CDCl3 at ᎑40 °C. The labeled cross-peaks are discussed in the text.
JChemEd.chem.wisc.edu • Vol. 75 No. 12 December 1998 • Journal of Chemical Education
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In the Laboratory
2D EXSY The 2D EXSY spectrum of MDACC in CD2Cl2 at ᎑40 °C is displayed in Figure 2. (For clarity, only cross-peaks above the diagonal are labeled; the cross-peaks below the diagonal are related by symmetry.) Interpretation of the spectrum requires a consideration of the mechanistic details given in Scheme I. The C-methyl groups labeled E and F are interconverted via C=C rotation and this gives rise to the cross-peak labeled 6 in Figure 2. Similarly, the cross-peaks labeled 2 and 3 arise owing to C–N rotations in both the E and Z isomers of MDACC. A careful consideration of Scheme I leads also to the cross-peaks labeled 1 and 4, which arise owing to C=C rotation as manifested by the exchange of N-methyl sites A with C and B with D, respectively. Since the chemical shifts of the N-methyl groups B and C are so similar, there is unfortunate overlap of cross-peaks 1 and 2, and 3 and 4. The fact that they are unresolved at 300 MHz leads to some uncertainty in the rate constants derived, although an upper limit on the C–N rotational barriers can be obtained. Cross-peak 5 may result from one of two possible mechanisms of exchange and is discussed later. Quantitative Analysis of 2D EXSY Data The rate constants for exchange of the C-methyl and Nmethyl groups in MDACC may be evaluated by integrating the diagonal peaks and cross-peaks of the 2D EXSY spectrum. Most commercial NMR spectrometers have the appropriate software to measure the 2D EXSY peak volumes. The peak volumes (IAA and IBB for diagonal peaks; IAB and IBA for crosspeaks) are converted into rate constants via a simple two-site exchange relationship: k = 1 ln r + 1 t mix r – 1
(2)
where r = 4X AX B (I AA + I BB )/(I AB + I BA ) – (XA – X B ) 2, XA and XB are the mole fractions of site A and site B, and tmix is the mixing time used in the 2D EXSY (11). From the rate constants, the rotational barriers may be calculated using the Eyring equation. Table 1 shows typical data derived from 2D EXSY analyses for MDACC. The decrease in the C=C rotational barrier in MDACC as a function of increasing solvent dielectric constant (ε) supports the notion that a solvent such as acetone is better able Table 1. Rotational Barriers in MDACC Solvent Rotation
Compound
Dielectric Strength (ε)
∆G‡/kcal mol᎑1
C=C
CDCl3 CD2Cl2 CD3C(O)CD3
4.7 8.9 20.7
14.7 14.3 (14.9 a) 14.0
C–N (E)
CDCl3 CD2Cl2 CD3C(O)CD3
4.7 8.9 20.7
13.5 13.2 (12.1 a)
