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Conformational study of 1,2-dithiacyclononane
SpectrochimicaAda, Vol. 4SA, No. 3, pp. 321-327, 1989. Printed in Gnat Britain.
0
Conformational
BORIS WEISS-L•
Department (Received
study of 1,2-dithiacyclononane
PEZ,? CHARLES P. NASH and NANCY
of Chemistry,
University
1 June 1988; infinalform
of California, 18 August
05%8539/89 S3.OOf0.00 1989 Pergamon Press pk
*
S. TRUE
Davis, CA 95616, U.S.A.
1988; accepted
18 August
1988)
Abstract-The temperature dependence of the Raman spectrum of 1,2-dithiacyclononane (1,2-DTCN) in the S-S stretching region has been used to infer the existence of a conformational equilibrium with AH” = 5.0 + 0.8 kJ/mol. Molecular mechanics calculations predict a (2 2 5)-C* lowest energy conformation in equilibrium with a (2 3 4) structure. The fully decoupled 13C NMR spectrum at - 80°C and the Raman spectra are consistent with this postulate. The temperature dependence of the ‘H NMR spectrum of 1,2DTCN is characteristic of the ring inversion process. A crude lineshape analysis allows us to calculate AC” =49.0* 1.2 kJ/mol.
INTRODUCTION The conformational
analysis of medium
size rings has
been a very active
field of research during the last two decades. Vibrational and NMR spectroscopies are the most common experimental techniques used in such studies. Of particular interest are the conformational changes that may occur when a methylene group is replaced by a heteroatom [1,2]. Because of the biological implications, a fair amount of attention has been paid to systems having one or more sulphur atoms in the ring. Work has been done on seven [S], eight [4], and higher membered rings [S, 61, but less is known about the behavior of sulphur-containing nine membered rings [3,7,8]. In this paper we present a conformational study of 1,2-dithiacyclononane (1,2-DTCN), carried out using Raman, proton and ’ 3C NMR spectroscopies, and molecular mechanics calculations [9]. EXPERIMENTAL
Raman measurement 1,2-DTCN, a liquid at room temperature, was synthesized using methods described before [lo]. Raman spectra of the neat liquid sealed in a glass capillary at different temperatures were obtained with a Spex Ramalab Raman spectrophotometer, using a 2 cm-’ slit width. The excitation source was the 488 nm Ar+ line of a Spectra Physics Model 164-02 laser, equipped with an interference filter. The temperature of the sample was controlled by pumping a thermostatted ethanol-water mixture through a jacket that surrounded the sample capillary. The temperature immediately adjacent to the sample was measured to within +0.2”C using a coppe-constantan thermocouple previously calibrated against a four-lead platinum resistance thermometer. The thermocouple reference junction was immersed in a triple point cell, and the output voltage measured with a
*Results presented at the XVIII Congreso Latinoamericane de Quimica, Enero (1988), Santiago, Chile. t Present address: Departamento de Quimica, Facultad de Ciencias, Universidad de Chile, Las Palmeras # 3425, Casilla 653, Santiago, Chile.
Hewlett-Packard 3468A digital multimeter. With this arrangement we were able to achieve temperature measurement and control over the range from -25 to +25”C. NMR
measurements
Proton NMR spectra were recorded with a Nicolet 11.80 T FT-NMR spectrometer, with proton observation at 500 MHz. The sample was prepared in a 5 mm high quality sample tube (Wilmad) at a concentration of about 1.0% mol of 1,2-DTCN in CS2 (Mallinkrodt) with CDCI, (Aldrich NMR Grade) and TMS (Aldrich NMR Grade) added for locking and reference purposes. Transients were acquired in 8k memory blocks. Between 50 to 100 transients were added to obtain spectral signal to noise ratios greater than 500. The temperature was regulated to + O.l”C and calibrated with a copper-constantan thermocouple placed in a 5 mm tube filled with CS,. The amount of sample in the tube and the nitrogen flow rate through the probe were optimized to minimize temperature gradients within the sample. The sample was allowed at least 20 min for thermal equilibration at each temperature where data was obtained. The fully decoupled 13C NMR spectrum was recorded at 90 MHz, using a 7.08 T GE NT FT-NMR spectrometer. The sample was prepared in a 10 mm high quality sample tube (Wilmad), at a concentration of 50% in CDCI,. A trace of TMS was added as a frequency reference. Calculations The analysis of the NMR data and the molecular mechanics calculations were done on a VAX 1l/750 minicomputer. The deconvolution of Raman spectral data, assuming Gaussian lineshape, was done on a Zenith Z-200 microcomputer using a curve fitting program based on the nonlinear FLETCHER and POWELL minimization technique [I 11. The program was written in BASIC and is menu driven. It provides graphical output of the function and the experimental data to visualize the quality of the fit. Areas of the individual peaks were calculated using Simpson’s rule.
RESULTS AND DISCUSSION
The Raman spectra of molecules containing disulphide bonds show intense S-S stretching bands in the SO&550 cm-’ region. It has been shown that the disulphide stretching frequency is sensitive to the local conformation of the CCSSCC fragment [12-173. The Raman spectrum of lJ-DTCN shows two peaks in this region, at 521 and 509 cm- ‘. Their relative in-
\r
BORISWEISS-LOPEZet al.
322
tensities vary reversibly with temperature in the manner shown in Fig. 1. A 521 cm-’ vibration in a cyclic disulphide can arise from either a conformation of the CCSSCC moiety having two CCSS torsion angles in the 110 range or from a gauche-gauche-Pans (g-g-t) conformation with one CCSS torsion angle near 180” [16]. This latter conformation cannot be realized in a ninemembered ring. A 509 cm - ’ vibration can arise from a wide range of nominally g-g-g conformations. There is a suggestion in our previous results that closing a CCSS torsion angle below 40” might decrease the disulphide stretching frequency. Thus a conformation with one “large” and one “small” CCSS torsion angle could have a 509 cm- 1 vibration frequency. The prominent peak at 490 cm- 1in Fig. 1 probably arises from the breathing mode of the ring. A crude normal coordinate calculation that used a mass 14 pseudo-atom approximation for the CH, groups and a Urey-Bradley force field optimized to fit the spectra of cyclic disulphides [16] produces exactly this result. In addition, in the room temperature FT-i.r. spectrum of the neat liquid, the 490 cm- ’ peak is only half as intense as the 521 cm- ’ peak whereas the relative intensities of the 509 and 521 cm- ’ peaks are essentially the same as those observed in the room temperature Raman spectrum. Four Raman spectra recorded over the temperature range from + 22 to - 11.4”C were each deconvoluted into three Gaussian components. An apparent equilibrium constant, Kapp, was defined as the ratio of the area of the “509” Gaussian to the area of the “521” Gaussian. Figure 2 shows the van’t Hoff plot from which an apparent AH0 of 5.0+0X kJ/mol for the process 521 cm -‘*509 cm-l conformers is calculated.
Roman shift
(cm-‘)
Fig. 1. Raman spectra of 1,2-DTCN at two different temperatures. The signals at 521 and 509 cm-’ are assigned to the S-S stretching of conformations (2 2 5)-C, and (2 3 4) respectively.
041 02
Y
5
0
33
35
0\ \ 37
39
lOOO/ TY K 1
Fig. 2. Van? Hoff plot for 1,2-DTCN conformational equilibrium. K,,, is defined in the text.
In order to obtain more information about the nature of the different conformers involved in this conformational equilibrium, we used the program MM2 [18] to explore the stable structures of 1,2DTCN. As a starting point, results reported for cyclononane [19] and molecular models were used. We found at least eight conformations with relative energies below 25 kJ/mol. Torsional angles and relative energies for the five lowest energy conformers are listed in Table 1. DALE’S nomenclature has been used to classify the different species [20]. Table 1 shows two nearly degenerate lowest energy structures which can be classified as (2 2 5) and (9). There is experimental evidence (see below) that conformation (9) is either a kinetically forbidden structure or an artifact of the force field. The calculated value of the relative energy difference between the (2 2 5)-CZ and the (2 3 4) conformations, AEMMz= 4.85 kJ/mol, agrees remarkably well with the apparent enthalpy difference obtained from the Raman temperature dependence study. It is especially noteworthy that the calculated (2 2 5)-C, conformation has two CCSS torsion angles of 109” and should therefore have the higher vibrational frequency [ 161. We thus conclude that the observed equilibrium probably involves principally these two conformers. The fact that this process is readily reversible suggest the existence of a low energy path for their interconversion. It is easy to see that the (2 3 4) conformer can be obtained by driving the torsion angle involving atoms 2,3,4,5 of the (2 2 5)-C, conformer from - 55” to +65”. A different but equivalent (2 3 4) structure is generated by driving torsion 7,8,9,1 by the same amount. Driving both torsions gives the (3,3,3)-C, conformer. A MM2 calculation of the process just described before was performed and the result is shown in Fig. 3. In these calculations the driven torsion is frozen at the new position and the rest of the geometry optimized. This is a standard feature of the MM2 software.
Conformational
study of 1,2-dithiacyclononane
323
Table 1. Torsion angles and MM2 relative energies for different conformations of 1,2-DTCN Conformationst Torsion angle *
WA4 (2,3,4,5) W,W
(4,5,6,7) (5,6,7,8) (67,859 C’,WS) W?L2)
(%1,2,3) Relative energy5
(2 2 5)-C,
(2 3 4)
109 -55 -71 72 72 -71 -55 109 -91
131 -51 -63 70 56 -149 63 29 -99
0.0
4.85
(3 3 3)-C* 51 64 -137 56 56 -137 64 51 -116 6.61
(9)-C, $
(9)$
88 -84 118 -69 -69 117 -84 88 -114
118 -95 60 -94 155 -60 -54 103 -101
6.65
0.25
*In degrees. TThe notation follows DALE [20]. $ANET and KRANE [19] classified structures of this type as (1 4 4). §In kJ/mol. [2251-C,
67 T,,T,=CCCS
c3331 -cp
Fig. 3. MM2 potential energy surface for the (2 2 5)-C, +(2 3 4)+(3 3 3)-C, interconversion.
If one assumes that the only significant difference in the partition functions of the (2 2 5)-C, and each of the degenerate (2 3 4) conformers of 1,2-DTCN comes from the presence of the symmetry number in the rotational factor, the entropy of any of the (2 3 4) species is then greater than that of the (2 2 5)-C, by Rln 2. This value in conjunction with AH0 allow us to estimate the equilibrium constant. At 300 K the populations are ca 64% and 36% for the (2,2,5)-C, and (2,3,4) respectively. This analysis assumes that no other conformation is being populated. There is a few per cent of (3,3,3)-C, present in the liquid at this temperature. It is known that cyclic disulphides are composed of two enantiomeric forms, and the two optical isomers are in equilibrium. The rate determining step in the interconversion of the two enantiomers is the hindered rotation around the disulphide bond [21]. It has been observed that this barrier ranges from ca 40 to
80 kJ/mol [4,21], depending on the nature of the ring and the value of the CSSC torsion angle [22], which makes this process particularly suitable for study using dynamic NMR. The ring inversion process of 1,2-DTCN affects the low temperature proton NMR spectrum. At 500 MHz the coalescence temperature is ca - 30°C. The proton NMR spectra of 1,2-DTCN at three different temperatures are shown in Fig. 4. At high temperature the spectrum shows three signals, at 1.6, 1.8 and 2.7 ppm downfield from TMS, which integrate to 6, 4 and 4 protons respectively. These are assigned to protons attached to carbons 5,6,7; 4,8; and 3,9 respectively. At low temperature the spectrum shows signals from protons at six different sites, which integrate (from high to low held) for 4,2,2,2,2 and 2 protons. A tentative assignment can be made on the basis of axial and equatorial positions at different carbons. The two low field signals correspond to the axial and equa-
BORISWEISS-LOPEZet al.
324
torial protons attached to carbons 3 and 9 which are bonded to sulphur. Considering the complexity of the spin system, it is difficult to perform a complete line shape analysis calculation. The proton NMR spectrum of cyclohex-
DTCN/CS2/TMS
ane near coalescence has been successfully analyzed. Rate constants and activation parameters were obtained treating the molecule as an AB spin system. including just the geminal coupling [23]. Using the program DNMRS [25] we have calculated the rate
35 OC SOOMHZ
4
6
Fig. 4a. DTCN/CS2/TMS
-32C
JOOMHZ
-32Y
Fig. 4b.
Conformational study of 1,2-dithiacyclononane DTCN/C%?/TMS
28
-70C
325
SOOMHZ
26
24
22
2
18
16
14
12
PPM
Fig. 4. Temperature dependence of the ‘H NMR spectrum of 1,ZDTCN. At low temperature the signals are tentatively assigned (from high to low field) as follows: four axial protons at carbons 4,5,7 and 8; two
symmetric protons at carbon 6, two equatorial protons at carbons 5 and 7; two equatorial protons at carbons 4 and 8; two axial protons at carbons 3 and 9; two equatorial protons at carbons 3 and 9.
constant of the ring inversion process of 1,2-DTCN near coalescence. Considering just the low field signals and treating them as an AB spin system neglecting all the couplings but the geminal, we obtained a first order rate constant K = 70 f 7 (Hz) at - 30°C. The uncertainty in the rate constant is primarily due to uncertainties in the limiting chemical shifts of the axial and equatorial protons attached to carbons 3 and 9. The chemical shift difference is ca 8 1.O Hz at - 90°C and decreases to ca 62.6 Hz at - 70°C. Values used in the rate analysis were obtained from a linear extrapolation. A complete analysis of the uncertainties introduced from the approximations used in the study of dynamic processes by NMR spectroscopy has been reported [24]. The maximum estimated uncertainty in the rate constant introduced by the approximation used in the present study is less than 10%. Using Eyring’s equation and assuming a transmission coefficient K = 0.5, a AG’ of 49.0 f 1.2 kJ/mol is calculated. The estimated uncertainty reflects a 10% uncertainty in the rate constant. This value is in good agreement with barriers reported before in similar systems [4, 21, 261. In an attempt to find a reasonable path for the ring inversion process we made another series of MM2 calculations. After many attempts we found a possible pathway which involves driving four torsions successively. The torsions driven and the necessary energies are shown in Fig. 5. The existence of other paths
6
w4567
/
16.7
1
WI987
t
Fig. 5. Interconversion scheme of 1,2-DTCN. Relative energies of the conformers in kJ/mol are given inside the rings. Energy barriers in kJ/mol are given beside the arrows. Circled atoms are “corners” according to DALE [19].
BORISWEISS-LOPEZ et al.
326
TMS
40
30
2.0
IO
0
PPM
Fig. 6. Fully decoupled 13CNMR spectrum of 1,2-DTCN at -80°C. molecular
cannot be discounted. The MM2 result corroborates the proposition about the rate determining step of the reaction mentioned above. The fully decoupled 13CNMR spectrum of 1,2DTCN at - 80°C is shown in Fig. 6. It shows signals coming from four different sites. At 22 ppm downfield from TMS there is a signal that integrates for two nuclei; at 22.5 ppm downfield from TMS another signal integrates for two nuclei; at 26 ppm another signal integrates for one nucleus; and at 40 ppm the last signal integrates for two nuclei. Unless there is a very improbable coincidence in the chemical shifts of the various carbons among molecules having different conformations, this experimental evidence strongly supports a lowest energy conformation having CZ molecular symmetry. This result argues against the existence of structure (9) as an accessible conformation. For cyclononane, ANET and KRANE [19] report conformational energies that increase in the order (3 3 3)-D, < (2 2 5)X2 < (2 3 4). For 1,2-DTCN our results strongly suggest that the most stable conformation is (2 2 5)-C, while the MM2 calculations yield conformational energies that increase in the order (2 2 5)-C; < (2 3 4) < (3 3 3)-C,. Therelative energies of the (3 3 3)-CZ and (2 2 5)-C, conformations of these two molecules are determined principally by differences in the angle strain, torsional and non-bonded interaction terms in the potential function. Because the CS (1.81 A) and SS (2.02 A) bond distances are both considerably longer than the CC bond distance (1.54 A), the calculated angle strain energies in the various conformations of 1,2-DTCN are all greater than those in the parent hydrocarbon. A glance at Fig. 5 shows that the increase will be relatively much larger for the (3 3 3)-C2 conformation. As this figure also suggests, the angle strain effect is of intermediate magnitude for the (2 3 4) conformation. Beyond this, the CSSC torsion angle in the (3 3 3)-C,
The spectrum
is consistent
with a C,
symmetry.
conformation (- 116”) is considerably larger than the nominal value (- 90”) for this entity, thereby further increasing the relative energy of the (3 3 3)-C, conformer. In the (2 3 4) conformation of 1,2-DTCN the calculated torsional energy contribution actually decreases compared to the (2 3 4) conformation of the parent hydrocarbon owing to relaxations elsewhere in the molecule. These same relaxations also yield a smaller calculated nonbonded interaction energy in the (2 3 4) conformer of the disulphide than is found for the same structure in cyclononane. In both their crystals [3,7] and in the gas phase 183, 1,4,7-trithiacyclononane and 1,5-dithiacyclononane adopt symmetrical (3 3 3) conformations. According to SETZER et al. [3] transannular sulphur-sulphur lone pair interactions play a significant role in establishing the conformations of these and other mesocyclit molecules containing sulphur atoms in positions 1,4; 1,5; or 1,6. In 1,2-DTCN transannular effects are absent. Here the lone pair interactions are reflected in the torsional potential of the disulphide bond. REFERENCES T. C. ROUNDS and H. L. STRAUSS, J. phys. Cl1 P. W. PAKES, Chem. 85, 2469 (1981).
.I.DALE,F. A. ANETand J. KRANE, J. them. VI G. BORGEN, Sot. Chem. Commun. 243 (1974).
G. S. WILSONand R. S. GLASS,Tetrahec31 W. N. SETZER, dron 37, 2735 (1981).
and H. J. ROSENMBAUM, Monats. 98, c41 A. LU~~INGHAUSS 1323 (1967).
Dissertation, University of Freiburg, PI P. ECKHARDT, F.R.G. (1968). J. DALE, Acta them. stand. 27, 1115 (1973). J. Am. ;;; R. S. GLASS,G. S. WILSONand W. N. SETZER, them. Sot. 102, 5068 (1980).
and R. S. PI W. N. SETZER,B. R. COLEMAN,G. S. WILSON GLASS. Tetrahedron
37.2743
(1981).
c91 N. L. ALLINGER,J. Am. them: Soc.‘99, 8127 (1977). Dissertation, University of California, Cl01 K. WILLIAMS,
Davis, CA (1983).
Conformational
[11] [12] [13] [14]
[15] [16] [17] Cl83
study of 1,2-dithiacyclononane
R. FLETCHERand M. J. D. POWELL, Comput. .I. 6, 163 (1963). H. SUGETA,Spectrochim. Acta 31A, 1729 (1975). H. E. VANWART and H. A. SCHERAGA, J. phys. Chem. 80, 1812 (1976). C. P. NASH,M. M. OLMSTEAD,B. WEISS-LOPEZ,W. K. MUSKER, N. RAMASUBBUand R. PARTHASARATHY, J. Am. &em. Sot. 107,7194 (1985). A. H. KUPTSOV and V. I. TROFIMOV,J. Biomolec. Struct. Dyn. 3, 185 (1985). B. WEISS-LOPEZ,M. H. GOODROW,W. K. MUSKERand C. P. NASHJ. Am. hem. Sot. 108, 1271 (1986). H. E. VAN WART and H. A. SCHERAGA,Proc. Natn. Acad. Sci. U.S.A. 83, 3064 (1986). N. ALLINGERand Y. H. YUH, Program MM2, QCPE
327
Catalog Number 395. F. A. ANET nnd J. KRANE, Israel J. Chem. 20,72 (1980). J. DALE, Topics Stereochem. 9, 199 (1976). G. CLAESON, G. ANDROES and M. CALVIN, J. Am. &em. Sot. 83, 4357 (1961). [22] M. CALVIN,Fedn Proc. Fedn Am. Sots exp. Biol. 13,697 (1954). [23] B. D. Ross and N. S. TRUE, J. Am. hem. Sot. 105,487l (1983). [24] A. ALLERHAND,H. S. GUTOWSKY,J. JONASand R. A. MEINZER,J. Am. them. Sot. 88, 3185 (1966). [25] D. S. STEPHENSON and G. BINSCH,Program DNMRS, QCPE Catalog Number 365. [26] S. KABUSS,A. LUTTINGHAUSS, H. FRIEBOLIN and R. MECKE. Z. Naturf: ZlB, 320 (1966).
[19] [20] [21]
0
Conformational
BORIS WEISS-L•
Department (Received
study of 1,2-dithiacyclononane
PEZ,? CHARLES P. NASH and NANCY
of Chemistry,
University
1 June 1988; infinalform
of California, 18 August
05%8539/89 S3.OOf0.00 1989 Pergamon Press pk
*
S. TRUE
Davis, CA 95616, U.S.A.
1988; accepted
18 August
1988)
Abstract-The temperature dependence of the Raman spectrum of 1,2-dithiacyclononane (1,2-DTCN) in the S-S stretching region has been used to infer the existence of a conformational equilibrium with AH” = 5.0 + 0.8 kJ/mol. Molecular mechanics calculations predict a (2 2 5)-C* lowest energy conformation in equilibrium with a (2 3 4) structure. The fully decoupled 13C NMR spectrum at - 80°C and the Raman spectra are consistent with this postulate. The temperature dependence of the ‘H NMR spectrum of 1,2DTCN is characteristic of the ring inversion process. A crude lineshape analysis allows us to calculate AC” =49.0* 1.2 kJ/mol.
INTRODUCTION The conformational
analysis of medium
size rings has
been a very active
field of research during the last two decades. Vibrational and NMR spectroscopies are the most common experimental techniques used in such studies. Of particular interest are the conformational changes that may occur when a methylene group is replaced by a heteroatom [1,2]. Because of the biological implications, a fair amount of attention has been paid to systems having one or more sulphur atoms in the ring. Work has been done on seven [S], eight [4], and higher membered rings [S, 61, but less is known about the behavior of sulphur-containing nine membered rings [3,7,8]. In this paper we present a conformational study of 1,2-dithiacyclononane (1,2-DTCN), carried out using Raman, proton and ’ 3C NMR spectroscopies, and molecular mechanics calculations [9]. EXPERIMENTAL
Raman measurement 1,2-DTCN, a liquid at room temperature, was synthesized using methods described before [lo]. Raman spectra of the neat liquid sealed in a glass capillary at different temperatures were obtained with a Spex Ramalab Raman spectrophotometer, using a 2 cm-’ slit width. The excitation source was the 488 nm Ar+ line of a Spectra Physics Model 164-02 laser, equipped with an interference filter. The temperature of the sample was controlled by pumping a thermostatted ethanol-water mixture through a jacket that surrounded the sample capillary. The temperature immediately adjacent to the sample was measured to within +0.2”C using a coppe-constantan thermocouple previously calibrated against a four-lead platinum resistance thermometer. The thermocouple reference junction was immersed in a triple point cell, and the output voltage measured with a
*Results presented at the XVIII Congreso Latinoamericane de Quimica, Enero (1988), Santiago, Chile. t Present address: Departamento de Quimica, Facultad de Ciencias, Universidad de Chile, Las Palmeras # 3425, Casilla 653, Santiago, Chile.
Hewlett-Packard 3468A digital multimeter. With this arrangement we were able to achieve temperature measurement and control over the range from -25 to +25”C. NMR
measurements
Proton NMR spectra were recorded with a Nicolet 11.80 T FT-NMR spectrometer, with proton observation at 500 MHz. The sample was prepared in a 5 mm high quality sample tube (Wilmad) at a concentration of about 1.0% mol of 1,2-DTCN in CS2 (Mallinkrodt) with CDCI, (Aldrich NMR Grade) and TMS (Aldrich NMR Grade) added for locking and reference purposes. Transients were acquired in 8k memory blocks. Between 50 to 100 transients were added to obtain spectral signal to noise ratios greater than 500. The temperature was regulated to + O.l”C and calibrated with a copper-constantan thermocouple placed in a 5 mm tube filled with CS,. The amount of sample in the tube and the nitrogen flow rate through the probe were optimized to minimize temperature gradients within the sample. The sample was allowed at least 20 min for thermal equilibration at each temperature where data was obtained. The fully decoupled 13C NMR spectrum was recorded at 90 MHz, using a 7.08 T GE NT FT-NMR spectrometer. The sample was prepared in a 10 mm high quality sample tube (Wilmad), at a concentration of 50% in CDCI,. A trace of TMS was added as a frequency reference. Calculations The analysis of the NMR data and the molecular mechanics calculations were done on a VAX 1l/750 minicomputer. The deconvolution of Raman spectral data, assuming Gaussian lineshape, was done on a Zenith Z-200 microcomputer using a curve fitting program based on the nonlinear FLETCHER and POWELL minimization technique [I 11. The program was written in BASIC and is menu driven. It provides graphical output of the function and the experimental data to visualize the quality of the fit. Areas of the individual peaks were calculated using Simpson’s rule.
RESULTS AND DISCUSSION
The Raman spectra of molecules containing disulphide bonds show intense S-S stretching bands in the SO&550 cm-’ region. It has been shown that the disulphide stretching frequency is sensitive to the local conformation of the CCSSCC fragment [12-173. The Raman spectrum of lJ-DTCN shows two peaks in this region, at 521 and 509 cm- ‘. Their relative in-
\r
BORISWEISS-LOPEZet al.
322
tensities vary reversibly with temperature in the manner shown in Fig. 1. A 521 cm-’ vibration in a cyclic disulphide can arise from either a conformation of the CCSSCC moiety having two CCSS torsion angles in the 110 range or from a gauche-gauche-Pans (g-g-t) conformation with one CCSS torsion angle near 180” [16]. This latter conformation cannot be realized in a ninemembered ring. A 509 cm - ’ vibration can arise from a wide range of nominally g-g-g conformations. There is a suggestion in our previous results that closing a CCSS torsion angle below 40” might decrease the disulphide stretching frequency. Thus a conformation with one “large” and one “small” CCSS torsion angle could have a 509 cm- 1 vibration frequency. The prominent peak at 490 cm- 1in Fig. 1 probably arises from the breathing mode of the ring. A crude normal coordinate calculation that used a mass 14 pseudo-atom approximation for the CH, groups and a Urey-Bradley force field optimized to fit the spectra of cyclic disulphides [16] produces exactly this result. In addition, in the room temperature FT-i.r. spectrum of the neat liquid, the 490 cm- ’ peak is only half as intense as the 521 cm- ’ peak whereas the relative intensities of the 509 and 521 cm- ’ peaks are essentially the same as those observed in the room temperature Raman spectrum. Four Raman spectra recorded over the temperature range from + 22 to - 11.4”C were each deconvoluted into three Gaussian components. An apparent equilibrium constant, Kapp, was defined as the ratio of the area of the “509” Gaussian to the area of the “521” Gaussian. Figure 2 shows the van’t Hoff plot from which an apparent AH0 of 5.0+0X kJ/mol for the process 521 cm -‘*509 cm-l conformers is calculated.
Roman shift
(cm-‘)
Fig. 1. Raman spectra of 1,2-DTCN at two different temperatures. The signals at 521 and 509 cm-’ are assigned to the S-S stretching of conformations (2 2 5)-C, and (2 3 4) respectively.
041 02
Y
5
0
33
35
0\ \ 37
39
lOOO/ TY K 1
Fig. 2. Van? Hoff plot for 1,2-DTCN conformational equilibrium. K,,, is defined in the text.
In order to obtain more information about the nature of the different conformers involved in this conformational equilibrium, we used the program MM2 [18] to explore the stable structures of 1,2DTCN. As a starting point, results reported for cyclononane [19] and molecular models were used. We found at least eight conformations with relative energies below 25 kJ/mol. Torsional angles and relative energies for the five lowest energy conformers are listed in Table 1. DALE’S nomenclature has been used to classify the different species [20]. Table 1 shows two nearly degenerate lowest energy structures which can be classified as (2 2 5) and (9). There is experimental evidence (see below) that conformation (9) is either a kinetically forbidden structure or an artifact of the force field. The calculated value of the relative energy difference between the (2 2 5)-CZ and the (2 3 4) conformations, AEMMz= 4.85 kJ/mol, agrees remarkably well with the apparent enthalpy difference obtained from the Raman temperature dependence study. It is especially noteworthy that the calculated (2 2 5)-C, conformation has two CCSS torsion angles of 109” and should therefore have the higher vibrational frequency [ 161. We thus conclude that the observed equilibrium probably involves principally these two conformers. The fact that this process is readily reversible suggest the existence of a low energy path for their interconversion. It is easy to see that the (2 3 4) conformer can be obtained by driving the torsion angle involving atoms 2,3,4,5 of the (2 2 5)-C, conformer from - 55” to +65”. A different but equivalent (2 3 4) structure is generated by driving torsion 7,8,9,1 by the same amount. Driving both torsions gives the (3,3,3)-C, conformer. A MM2 calculation of the process just described before was performed and the result is shown in Fig. 3. In these calculations the driven torsion is frozen at the new position and the rest of the geometry optimized. This is a standard feature of the MM2 software.
Conformational
study of 1,2-dithiacyclononane
323
Table 1. Torsion angles and MM2 relative energies for different conformations of 1,2-DTCN Conformationst Torsion angle *
WA4 (2,3,4,5) W,W
(4,5,6,7) (5,6,7,8) (67,859 C’,WS) W?L2)
(%1,2,3) Relative energy5
(2 2 5)-C,
(2 3 4)
109 -55 -71 72 72 -71 -55 109 -91
131 -51 -63 70 56 -149 63 29 -99
0.0
4.85
(3 3 3)-C* 51 64 -137 56 56 -137 64 51 -116 6.61
(9)-C, $
(9)$
88 -84 118 -69 -69 117 -84 88 -114
118 -95 60 -94 155 -60 -54 103 -101
6.65
0.25
*In degrees. TThe notation follows DALE [20]. $ANET and KRANE [19] classified structures of this type as (1 4 4). §In kJ/mol. [2251-C,
67 T,,T,=CCCS
c3331 -cp
Fig. 3. MM2 potential energy surface for the (2 2 5)-C, +(2 3 4)+(3 3 3)-C, interconversion.
If one assumes that the only significant difference in the partition functions of the (2 2 5)-C, and each of the degenerate (2 3 4) conformers of 1,2-DTCN comes from the presence of the symmetry number in the rotational factor, the entropy of any of the (2 3 4) species is then greater than that of the (2 2 5)-C, by Rln 2. This value in conjunction with AH0 allow us to estimate the equilibrium constant. At 300 K the populations are ca 64% and 36% for the (2,2,5)-C, and (2,3,4) respectively. This analysis assumes that no other conformation is being populated. There is a few per cent of (3,3,3)-C, present in the liquid at this temperature. It is known that cyclic disulphides are composed of two enantiomeric forms, and the two optical isomers are in equilibrium. The rate determining step in the interconversion of the two enantiomers is the hindered rotation around the disulphide bond [21]. It has been observed that this barrier ranges from ca 40 to
80 kJ/mol [4,21], depending on the nature of the ring and the value of the CSSC torsion angle [22], which makes this process particularly suitable for study using dynamic NMR. The ring inversion process of 1,2-DTCN affects the low temperature proton NMR spectrum. At 500 MHz the coalescence temperature is ca - 30°C. The proton NMR spectra of 1,2-DTCN at three different temperatures are shown in Fig. 4. At high temperature the spectrum shows three signals, at 1.6, 1.8 and 2.7 ppm downfield from TMS, which integrate to 6, 4 and 4 protons respectively. These are assigned to protons attached to carbons 5,6,7; 4,8; and 3,9 respectively. At low temperature the spectrum shows signals from protons at six different sites, which integrate (from high to low held) for 4,2,2,2,2 and 2 protons. A tentative assignment can be made on the basis of axial and equatorial positions at different carbons. The two low field signals correspond to the axial and equa-
BORISWEISS-LOPEZet al.
324
torial protons attached to carbons 3 and 9 which are bonded to sulphur. Considering the complexity of the spin system, it is difficult to perform a complete line shape analysis calculation. The proton NMR spectrum of cyclohex-
DTCN/CS2/TMS
ane near coalescence has been successfully analyzed. Rate constants and activation parameters were obtained treating the molecule as an AB spin system. including just the geminal coupling [23]. Using the program DNMRS [25] we have calculated the rate
35 OC SOOMHZ
4
6
Fig. 4a. DTCN/CS2/TMS
-32C
JOOMHZ
-32Y
Fig. 4b.
Conformational study of 1,2-dithiacyclononane DTCN/C%?/TMS
28
-70C
325
SOOMHZ
26
24
22
2
18
16
14
12
PPM
Fig. 4. Temperature dependence of the ‘H NMR spectrum of 1,ZDTCN. At low temperature the signals are tentatively assigned (from high to low field) as follows: four axial protons at carbons 4,5,7 and 8; two
symmetric protons at carbon 6, two equatorial protons at carbons 5 and 7; two equatorial protons at carbons 4 and 8; two axial protons at carbons 3 and 9; two equatorial protons at carbons 3 and 9.
constant of the ring inversion process of 1,2-DTCN near coalescence. Considering just the low field signals and treating them as an AB spin system neglecting all the couplings but the geminal, we obtained a first order rate constant K = 70 f 7 (Hz) at - 30°C. The uncertainty in the rate constant is primarily due to uncertainties in the limiting chemical shifts of the axial and equatorial protons attached to carbons 3 and 9. The chemical shift difference is ca 8 1.O Hz at - 90°C and decreases to ca 62.6 Hz at - 70°C. Values used in the rate analysis were obtained from a linear extrapolation. A complete analysis of the uncertainties introduced from the approximations used in the study of dynamic processes by NMR spectroscopy has been reported [24]. The maximum estimated uncertainty in the rate constant introduced by the approximation used in the present study is less than 10%. Using Eyring’s equation and assuming a transmission coefficient K = 0.5, a AG’ of 49.0 f 1.2 kJ/mol is calculated. The estimated uncertainty reflects a 10% uncertainty in the rate constant. This value is in good agreement with barriers reported before in similar systems [4, 21, 261. In an attempt to find a reasonable path for the ring inversion process we made another series of MM2 calculations. After many attempts we found a possible pathway which involves driving four torsions successively. The torsions driven and the necessary energies are shown in Fig. 5. The existence of other paths
6
w4567
/
16.7
1
WI987
t
Fig. 5. Interconversion scheme of 1,2-DTCN. Relative energies of the conformers in kJ/mol are given inside the rings. Energy barriers in kJ/mol are given beside the arrows. Circled atoms are “corners” according to DALE [19].
BORISWEISS-LOPEZ et al.
326
TMS
40
30
2.0
IO
0
PPM
Fig. 6. Fully decoupled 13CNMR spectrum of 1,2-DTCN at -80°C. molecular
cannot be discounted. The MM2 result corroborates the proposition about the rate determining step of the reaction mentioned above. The fully decoupled 13CNMR spectrum of 1,2DTCN at - 80°C is shown in Fig. 6. It shows signals coming from four different sites. At 22 ppm downfield from TMS there is a signal that integrates for two nuclei; at 22.5 ppm downfield from TMS another signal integrates for two nuclei; at 26 ppm another signal integrates for one nucleus; and at 40 ppm the last signal integrates for two nuclei. Unless there is a very improbable coincidence in the chemical shifts of the various carbons among molecules having different conformations, this experimental evidence strongly supports a lowest energy conformation having CZ molecular symmetry. This result argues against the existence of structure (9) as an accessible conformation. For cyclononane, ANET and KRANE [19] report conformational energies that increase in the order (3 3 3)-D, < (2 2 5)X2 < (2 3 4). For 1,2-DTCN our results strongly suggest that the most stable conformation is (2 2 5)-C, while the MM2 calculations yield conformational energies that increase in the order (2 2 5)-C; < (2 3 4) < (3 3 3)-C,. Therelative energies of the (3 3 3)-CZ and (2 2 5)-C, conformations of these two molecules are determined principally by differences in the angle strain, torsional and non-bonded interaction terms in the potential function. Because the CS (1.81 A) and SS (2.02 A) bond distances are both considerably longer than the CC bond distance (1.54 A), the calculated angle strain energies in the various conformations of 1,2-DTCN are all greater than those in the parent hydrocarbon. A glance at Fig. 5 shows that the increase will be relatively much larger for the (3 3 3)-C2 conformation. As this figure also suggests, the angle strain effect is of intermediate magnitude for the (2 3 4) conformation. Beyond this, the CSSC torsion angle in the (3 3 3)-C,
The spectrum
is consistent
with a C,
symmetry.
conformation (- 116”) is considerably larger than the nominal value (- 90”) for this entity, thereby further increasing the relative energy of the (3 3 3)-C, conformer. In the (2 3 4) conformation of 1,2-DTCN the calculated torsional energy contribution actually decreases compared to the (2 3 4) conformation of the parent hydrocarbon owing to relaxations elsewhere in the molecule. These same relaxations also yield a smaller calculated nonbonded interaction energy in the (2 3 4) conformer of the disulphide than is found for the same structure in cyclononane. In both their crystals [3,7] and in the gas phase 183, 1,4,7-trithiacyclononane and 1,5-dithiacyclononane adopt symmetrical (3 3 3) conformations. According to SETZER et al. [3] transannular sulphur-sulphur lone pair interactions play a significant role in establishing the conformations of these and other mesocyclit molecules containing sulphur atoms in positions 1,4; 1,5; or 1,6. In 1,2-DTCN transannular effects are absent. Here the lone pair interactions are reflected in the torsional potential of the disulphide bond. REFERENCES T. C. ROUNDS and H. L. STRAUSS, J. phys. Cl1 P. W. PAKES, Chem. 85, 2469 (1981).
.I.DALE,F. A. ANETand J. KRANE, J. them. VI G. BORGEN, Sot. Chem. Commun. 243 (1974).
G. S. WILSONand R. S. GLASS,Tetrahec31 W. N. SETZER, dron 37, 2735 (1981).
and H. J. ROSENMBAUM, Monats. 98, c41 A. LU~~INGHAUSS 1323 (1967).
Dissertation, University of Freiburg, PI P. ECKHARDT, F.R.G. (1968). J. DALE, Acta them. stand. 27, 1115 (1973). J. Am. ;;; R. S. GLASS,G. S. WILSONand W. N. SETZER, them. Sot. 102, 5068 (1980).
and R. S. PI W. N. SETZER,B. R. COLEMAN,G. S. WILSON GLASS. Tetrahedron
37.2743
(1981).
c91 N. L. ALLINGER,J. Am. them: Soc.‘99, 8127 (1977). Dissertation, University of California, Cl01 K. WILLIAMS,
Davis, CA (1983).
Conformational
[11] [12] [13] [14]
[15] [16] [17] Cl83
study of 1,2-dithiacyclononane
R. FLETCHERand M. J. D. POWELL, Comput. .I. 6, 163 (1963). H. SUGETA,Spectrochim. Acta 31A, 1729 (1975). H. E. VANWART and H. A. SCHERAGA, J. phys. Chem. 80, 1812 (1976). C. P. NASH,M. M. OLMSTEAD,B. WEISS-LOPEZ,W. K. MUSKER, N. RAMASUBBUand R. PARTHASARATHY, J. Am. &em. Sot. 107,7194 (1985). A. H. KUPTSOV and V. I. TROFIMOV,J. Biomolec. Struct. Dyn. 3, 185 (1985). B. WEISS-LOPEZ,M. H. GOODROW,W. K. MUSKERand C. P. NASHJ. Am. hem. Sot. 108, 1271 (1986). H. E. VAN WART and H. A. SCHERAGA,Proc. Natn. Acad. Sci. U.S.A. 83, 3064 (1986). N. ALLINGERand Y. H. YUH, Program MM2, QCPE
327
Catalog Number 395. F. A. ANET nnd J. KRANE, Israel J. Chem. 20,72 (1980). J. DALE, Topics Stereochem. 9, 199 (1976). G. CLAESON, G. ANDROES and M. CALVIN, J. Am. &em. Sot. 83, 4357 (1961). [22] M. CALVIN,Fedn Proc. Fedn Am. Sots exp. Biol. 13,697 (1954). [23] B. D. Ross and N. S. TRUE, J. Am. hem. Sot. 105,487l (1983). [24] A. ALLERHAND,H. S. GUTOWSKY,J. JONASand R. A. MEINZER,J. Am. them. Sot. 88, 3185 (1966). [25] D. S. STEPHENSON and G. BINSCH,Program DNMRS, QCPE Catalog Number 365. [26] S. KABUSS,A. LUTTINGHAUSS, H. FRIEBOLIN and R. MECKE. Z. Naturf: ZlB, 320 (1966).
[19] [20] [21]