.Condensation of 4-methylthiobenzaldehyde with 1-nitropropane unexpectedly afforded separable amounts of both (E)- and (Z)-1-(4-methylthiophenyl)-2-nitrobutene. The 1H and 13C NMR spectra allowed the unequivocal assignment of all signals and their correlation with the preferred conformations adopted by these compounds as determined by NOESY experiments. Hartree Fock theory optimizations at the 6-311G(d,p) level were carried out for the stereoisomeric 4-methylthionitroethene, -nitropropene, and -nitrobutene pairs, and the relative energy differences between isomers were calculated in order to estimate approximate E/Z equilibrium constants. These energy differences decrease with the increasing number of side chain carbon atoms, explaining the possibility of separating (E)- and (Z)-nitrobutenes and the failure to isolate the (Z) isomers of the lower homologues under the usual thermodynamically controlled reaction conditions.
J. Chil. Chem. Soc., 49, N 3 (2004): 257-260
GEOMETRICAL ISOMERISM IN β-NITROSTYRENES: PREFERRED CONFORMATIONS OF (E)- AND (Z)- 1-(4-METHYLTHIOPHENYL)-2-NITROBUTENES
CLAUDIO HURTADO-GUZMÁN, PATRICIO ITURRIAGA-VÁSQUEZ, GERALD ZAPATA-TORRES AND BRUCE K. CASSELS*
Millennium Institute for Advanced Studies in Cell Biology and Biotechnology, and Department of Chemistry, Faculty of Sciences, University of Chile, Santiago, Chile. E-mail:bcassels@uchile.cl.
(Received: November 4, 2003 - Accepted: July 12, 2004)
ABSTRACT
Condensation of 4-methylthiobenzaldehyde with 1-nitropropane unexpectedly afforded separable amounts of both (E)- and (Z)-1-(4-methylthiophenyl)-2-nitrobutene. The 1H and 13C NMR spectra allowed the unequivocal assignment of all signals and their correlation with the preferred conformations adopted by these compounds as determined by NOESY experiments. Hartree Fock theory optimizations at the 6-311G(d,p) level were carried out for the stereoisomeric 4-methylthionitroethene, -nitropropene, and -nitrobutene pairs, and the relative energy differences between isomers were calculated in order to estimate approximate E/Z equilibrium constants. These energy differences decrease with the increasing number of side chain carbon atoms, explaining the possibility of separating (E)- and (Z)-nitrobutenes and the failure to isolate the (Z) isomers of the lower homologues under the usual thermodynamically controlled reaction conditions.
Keywords: β-nitrostyrene geometrical isomers; preferred conformations; NMR studies; RHF/6-311G(d,p) calculations.
INTRODUCTION
β-Nitroolefins are widely used as substrates for nucleophilic additions.1,2 β-Nitrostyrenes are commonly prepared en route to β-phenylalkylamines, and nitro cycloalkenes have been reviewed as very versatile synthetic intermediates.3,4 The steric outcome of nucleophilic additions to these compounds depends on the configuration of the starting material, but both stereoisomers are seldom readily available, and β-nitrostyrenes and 1-nitroprop-2-enes obtained by the usual Knoevenagel sequence show a strong predominance of the (E)-isomer which is generally the sole isolated product. Only one literature reference reports obtaining (Z)-β-nitroolefins in good yield by dehydration of the corresponding nitro alcohol when the reaction is carried out at a very low temperature.5 A related example reports the elimination reaction of a 2-alkylthio-1-nitropropane with potassium fluoride to produce a mixture of both isomers with the (Z)-isomer predominating.6
We now report the separation and complete NMR spectroscopic characterization of both
-ethyl-β-nitrostyrene isomers, (E)-1a and (Z)-1a (Figure 1),
obtained by Knoevenagel condensation of
4-methylthiobenzaldehyde and 1-nitropropane as an approach to
novel monoamine oxidase inhibitors and possible serotonin
releasers.7
NOESY experiments provided evidence for the preferred
conformations of the products. In addition, we computed the
relative energy differences at the RHF/6-311G(d,p) level for this
(E)- and (Z)-1-(4-methylthiophenyl)-2-nitrobutene pair and the corresponding nitropropenes (1b) and ethenes (1c). RESULTS AND DISCUSSION
The (E) and (Z) isomers of 1-(4-methylthiophenyl)-2-nitrobutene were formed in the reaction mixture of 4-methylthiobenzaldehyde and 1-nitropropane in refluxing toluene, using N,N-dimethylethylenediamine as catalyst, in an approximately 92:8 molar ratio, judging from the 1H NMR spectrum of the crude product. Both products [(E)-1a and (Z)-1a, respectively] were separated chromatographically and fully characterized by 1H- and 13C-NMR spectroscopy, using HMBC, HMQC and NOESY experiments for complete assignment of the signals. Tables 1 and 2 allow direct comparison of the 1H and 13C chemical shifts of stereoisomers (E)-1a and (Z)-1a.
Fig. 2a. NOESY spectrum of (E)-1-(4-methylthiophenyl)-2-nitrobutene [(E)-1a] (CDCl3).
Fig. 2b. NOESY spectrum of (Z)-1-(4-methylthiophenyl)-2-nitrobutene [(Z)-1b] (CDCl3).
(E)-1-(4-Methylthiophenyl)-2-nitrobutene [(E)-1a] and (Z)-1-(4-Methylthiophenyl)-2-nitrobutene [(Z)-1a].
A mixture of 4-methylthiobenzaldehyde (1.3 ml, 0.010 mol), N,N-dimethylethylenediamine (1.3 ml, 0.010 mol), 1-nitropropane (4.5 ml, 0.041 mol) and toluene (10 ml) was refluxed for 24 h with continuous water removal under a Dean-Stark trap. All volatiles were removed under reduced pressure and the residue was fractionated chromatographically over silica gel, eluting with CHCl3, to afford the E [(E)-1a] (1.08 g, 92% in the mixture) and Z isomers [(Z)-1a] (0.096 g, 8% in the mixture) as viscous orange colored liquids.
(E)-1a: 1H-NMR (CDCl3) δ 1.28 (t, 3H, J = 7.4 Hz, CH2CH3), 2.52 (s, 3H, S-CH3), 2.88 (q, 2H, J = 7.4 Hz, CH3CH2C=CH), 7.29 (d, 2H, J = 8.5 Hz, H3' and H5'), 7.36 (d, 2H, J = 8.5 Hz, H2' and H6'), 7.98 (s, 1H, Ar-CH=C). HREIMS m/z (M+) = 223.06621; calc. for C11H13NO2S = 223.06670.
(Z)-1a: 1H-NMR (CDCl3) δ 1.20 (t, 3H, J = 7.4 Hz, CH2CH3), 2.46 (s, 3H, S-CH3), 2.67 (q, 2H, J = 7.4 Hz, CH3CH2C=CH), 6.29 (s, 1H, Ar-CH=C), 7.16 (apparent s, 4H, J = 9.2 Hz, Ar-H). HREIMS m/z (M+) = 223.06622; calc. for C11H13NO2S = 223.06670.
Journal of the Chilean Chemical Society
versión On-line ISSN 0717-9707
J. Chil. Chem. Soc. v.49 n.3 Concepción sep. 2004
http://dx.doi.org/10.4067/S0717-97072004000300013
| J. Chil. Chem. Soc., 49, N 3 (2004): 257-260 GEOMETRICAL ISOMERISM IN β-NITROSTYRENES: PREFERRED CONFORMATIONS OF (E)- AND (Z)- 1-(4-METHYLTHIOPHENYL)-2-NITROBUTENES CLAUDIO HURTADO-GUZMÁN, PATRICIO ITURRIAGA-VÁSQUEZ, GERALD ZAPATA-TORRES AND BRUCE K. CASSELS* Millennium Institute for Advanced Studies in Cell Biology and Biotechnology, and Department of Chemistry, Faculty of Sciences, University of Chile, Santiago, Chile. E-mail:bcassels@uchile.cl. (Received: November 4, 2003 - Accepted: July 12, 2004) |
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