Fourth International Electronic Conference on Synthetic Organic Chemistry (ECSOC-4), www.mdpi.org/ecsoc-4.htm, September 1-30, 2000

[C0038]

Dynamic Behaviour of Cyclic Thiohydroxamic Acid Derivatives – Barrier to Rotation about N–O bonds in 4-substituted N-Isopropoxythiazole-2(3H)-thiones and N-Isopropoxypyridine-2(1H)-thione

Jens Hartung*, Markus Heubes, Rainer Kneuer, Michaela Schwarz

Institut für Organische Chemie der Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany
Fax: +49 931 888 4606, E-mail: [email protected]

Received: 15 August 2000 / Uploaded: 20 August

Abstract: Activation parameters [DG‡200, DH‡, DS‡] for barriers to rotation about N–O bonds in N-isopropoxypyridine-2(1H)-thione (1) and two 4-substituted N-isopropoxythiazole-2(3H)-thiones 2 and 3 were determined by variable-temperature 1H (600 MHz) and 13C (150 MHz) NMR spectroscopy in the temperature range of T = 135–250 K. The barriers to rotation about N–O bonds in cyclic thiohydroxamic acid O-esters 1, 2, and 3 are explained by a superposition of steric and electronic effects.

Keywords: Barrier to rotation, Dynamic NMR, Pyridinethione, Thiazolethione, Nitrogen-Oxygen bond

Introduction

Recent advances in low temperature NMR studies[1] and the synthetic access to new mechanistic probes[2] have encouraged us to determine hitherto unknown barriers to rotation about N–O bonds in cyclic thiohydroxamic acid O-esters, e.g. N-isopropoxypyridine-2(1H)-thione (1) and the 4-substituted thiazolethiones 2 and 3 (Figure 1) .

Figure 1. Pyridinethione and thiazolethione-derived cyclic thiohydroxamic acid O-esters 1–3 (top) and topomerization of CH3 groups in N-isopropoxypyridinethione 1 via rotation about the sterogenic N–O bond (bottom).

Results

Thiones 1–3 were prepared according to standard procedures and were fully characterized.[2–6] Proton NMR spectra of thiones 1, 2, and 3 in either deuterochloroform or a mixture of chlorodifluoromethane and perdeuterodimethyl ether showed typical line patterns of unhindered rotating isopropyl groups at T = 293 K. Thus, topomerization of CH3 groups is fast with respect to the NMR time scale at that temperature. For example, a doublet at 1.04 ppm (1H NMR) and a singlet at 19.0 ppm (13C NMR) was recorded for both CH3 groups in N-isopropoxy-4-p-chlorophenyl)thiazole-2(3H)-thione (3). On cooling these signals broadened. Coalescence was observed at T = 235 K (13C NMR, Figure 2). If temperatures were further lowered, the topomerization (exchange) became slow with respect to the NMR time scale. At T = 200 K, well separated signals were recorded for both diastereotopic methyl groups at 19.4 ppm and 19.0 ppm in the 13C NMR spectrum of 3. The respective 1H resonance lines were observed at 0.69 ppm and at 1.23 ppm (both d, J = 4.5 Hz). Coalescence of signals and their separation into individual sets of resonances on further cooling were also observed for diastereotopic methyl groups in pyridinethione 1 (Tcoal ~ 145 K) and 4-methylthiazolethione 2 (Tcoal ~ 200 K).

Figure 2. Stacking plot of carbon-13 NMR spectra of N-isopropoxy-p-chlorophenylthiazolethione 3 at different temperatures.

Variable-temperature proton-NMR data were subjected to complete line-shape-analysis in order to derive rate constants k for the exchange process caused by the rotation about the N–O bond. Rate constants from carbon-13 NMR spectra were accessible by analyzing line widths of half height and shift differences Dn of exchange-related nuclei according to eq. 1 and eq. 2 with Wex(change) = Wobs(erved) – W ref(erence).[1] Line widths of C-5 (Figure 1) were taken as reference for pyridinethione 1, thiazolethiones 2, and 3. Experimental errors in k were estimated to be ± 5%. Temperatures were measured using a solution of a barbaralane-derived high-precision carbon-13 shift thermometer in chorodifluoromethane/perdeuterodimethyl ether [~ 3/1 (v/v)] which is suitable for a temperature range of T = 100–300 K.[7] Activation parameters DH‡, DS‡ (Table 1) were calculated from eq. 3.

Table 1. Activation parameters for N–O rotations in pyridinethione 1, and thiazolethiones 2 and 3.

[a] The reported uncertainties in DH‡, DS‡ refer to standard deviations while the error DG‡200 was calculated from the individual uncertainties in DH‡ and DS‡.

Discussion

The phenomenon of slowed rotation of substitutents which are covalently bound via heteroatom-heteroatom single bonds is well documented.[8–10] Two factors contribute to barriers of N–O rotation: (i) electronic (repulsion of lone pairs) and (ii) steric effects at nitrogen and oxygen. Cyclic thiohydroxamic acid O-esters adopt an almost orthogonal transposition of substituents at nitrogen and at oxygen in the solid state.[2,3] This arrangement would have been predicted by the VSEPR principle[11] alone if steric interactions were neglected. However, proton NMR spectra of N-isopropoxy substituted heterocycles 1, 2 and 3 in CDCl3 solution at room temperature indicate that topomerization of the methyl groups is fast with respect to the NMR time scale, since signals of both diastereotopic methyl groups are not split into separate sets of lines (Figures 1 and 2).[2–4] On cooling, topomerization of CH3 groups becomes slow and coalescence is observed. On further lowering of the temperature, exchange becomes slow with respect to the NMR time scale. Line-shape analyses and examination of widths of half height of exchange-related nuclei affords barriers to rotation about N–O bonds in thiones 1, 2 and 3 (Table 1). The lowest barrier was observed for pyridinethione 1 DG‡200 29 ± 2 kJ mol–1). 4-Substituted thiazolethiones 2 (DG‡200 42 ± 7 kJ mol–1) and 3 (DG‡200 46 ± 1 kJ mol–1] showed substantially higher barriers. Since the alkoxy moiety is identical in all compounds, the ranking of calculated DG‡200 values should majorly reflect steric contributions from heterocyclic part of the structures.

Conclusions

Activation parameters (DH‡, DS‡) for rotations about N–O single bonds in cyclic thiohydroxamic acid O-esters have been measured in the temperature range of 130–273 K by variable-temperature NMR experiments for the first time. Calculated DG‡200 values for N-isopropoxypyridine-2(1H)-thione (1) and two 4-substituted N-isopropoxythiazole-2(3H)-thiones 2 and 3 indicate that steric encroachment in vicinity of the N–O bond decelerates the underlying rotation process thus leading to higher barriers of activation.

Acknowledgement

This work was generously supported by the Fonds der Chemischen Industrie and the Deutsche Forschungsgemeinschaft (Ha 1705/5–1).

References

[1] L. M. Jackman, E. Fernandes, M. Heubes, H. Quast, Eur. J. Org. Chem. 1998, 2209–2227.

[2] J. Hartung, M. Schwarz, I. Svoboda, H. Fueß, M.–T. Duarte, Eur. J. Org. Chem. 1999, 1275–1290.

[3] J. Hartung, M. Hiller, M. Schwarz, I. Svoboda, H. Fuess, Liebigs Ann. 1996, 2091–2097.

[4] B.P. Hay, A.L.J. Beckwith, J. Org. Chem. 1988, 53, 4330–4334.

[5] J. Hartung, M. Heubes, R. Kneuer, M. Schwarz, manuscript in preparation.

[6] J. Hartung, R. Kneuer, M. Schwarz, I. Svoboda, H. Fueß, Eur. J. Org. Chem. 1999, 97–106.

[7] H. Quast, M. Heubes, A. Dunger, H.-H. Limbach, J. Magn. Reson. 1998, 134, 236–244.

[8] M. Raban, D. Kost, Tetrahedron 1984, 40, 3345–3381.

[9] F.G. Riddell, Tetrahedron, 1981, 37, 849–858.

[10] G. Binsch, H. Kessler, Angew. Chem. 1980, 92, 445–463, Angew. Chem., Int. Ed. Engl. 1980, 19, 411–459.

[11] [11a] R.J. Gillespie, Chem. Soc. Rev. 1992, 59–69. [11b] R. Gillespie, J. Chem. Educ. 1963, 40, 295–301.

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