Synthesis and a study of the 13 C NMR spectroscopic properties of positional isomers of some C 18 acetylenic thia fatty esters

This paper is dedicated to Dr. Douglas Lloyd on his 80 th birthday Abstract The carbon magnetic resonance spectra of four positional acetylenic thia fatty acid methyl ester isomers have been recorded to investigate the effect of the sulfur atom on the chemical shifts of the carbon nuclei adjacent to it


Introduction
2][3][4][5] Corey et al. 6,7 reported that the 7-thia-, 10-thia-and 13-thia-arachidonic acids are potent inhibitors in leukotriene (lipoxin) biosynthesis.This implies a possible means of controlling inflammatory diseases caused by an overproduction of the leukotrienes in the human body.Buist's group have demonstrated the enzymatic biomethylenation of 6-thia-oleic acid by the microorganism, Lactobacillus plantarum. 8Skrede et al. have reviewed the metabolism of thia fatty acids. 9ur group have synthesized and studied spectroscopic and mass spectrometric properties of the positional isomers of the methyl thialaurate, [10][11][12][13] ten methyl dithiastearate isomers 14 and the corresponding sulfinyl and sulfonyl derivatives of methyl thialaurate. 15In this paper, we describe the synthesis of a set of positional isomers of C 18 acetylenic thia fatty esters (5-8, Scheme 1) in an effort to study the effect of the sulfur atom on the chemical shifts of the carbon nuclei in the alkynyl chain of these thia fatty ester isomers by nuclear magnetic resonance spectroscopy.
The 13 C NMR chemical shifts of carbon nuclei are very susceptible to changes in the positions of the functional groups on the alkyl chains of fatty acids, making this analytical technique a much more informative one than 1 H NMR, especially in the confirmation of the structure of closely related fatty ester isomers.Bus et al. 16 have determined the shift parameters due to the acetylenic, cis-olefinic and trans-olefinic system on the carbon shifts of the adjacent methylene carbon atoms (Table 1).To establish the shift effects due to a sulfur atom on the neighbouring methylene carbon nuclei, di-n-decyl sulfide was used as a model compound for this purpose.We have used the same base values employed for an unperturbed carbon nucleus of a methylene group as reported by Bus et al. 16 and also the shift for a methyl and the carbonyl atom of the methyl ester group as 29.75, 14.10 and 174.35 ppm, respectively.The shift parameters due to a sulfur atom on the adjacent methylene carbons can therefore be established from the result of the 13 C NMR spectroscopic analysis of the di-n-decyl sulfide (Table 2).In the Table-2 we show the carbon shift values of the unperturbed methylene groups, but have included the shift values reported by Bus et al. for the methylene adjacent to the methyl group (namely the methylenes at the ω-1, ω-2, ω-3 and ω-4 position).
Table 2. Shift parameters due to the effect of the sulfur atom on the 13 C NMR shift values of the methylene carbon atoms of di-n-decyl sulfide +2.56 +0.10 -0.71 -0.39 -0.12 -0.02 -0.04 +0.09 +0.01 +0.01 The shift effect for a sulfur atom on the adjacent methylene carbon shifts was derived from the difference in values between the observed and the reported values of the shifts of the corresponding methylene carbon.From these results, it appeared that the sulphur atom exercised a deshielding effect on the α− and β−methylene groups while the sulphur atom showed a slight shielding effect on the γ, δ and ε−methylene shifts.It was possible by application of the 'the additivity rule' to estimate the carbon shifts of the various methylene carbon nuclei, including those of the acetylenic carbons, of the acetylenic thia isomers (5-8).The observed and estimated shift values are shown in Table 3.The detail calculation of the shift values of the carbon nuclei of the methyl 6-thia-10-octadecynoate ( 6) is given below as an example: Bus et al. 17 have reported the basic shift value of an unperturbed acetylenic carbon atom in a long chain fatty acid ester as 80.20 ppm.In the spectrum of compound 5, the effect of the sulfur atom allowed the acetylenic carbon nuclei to be characterized.The more downfield acetylenic signal was attributed to the shift of C-12.The effect of the sulfur atom increases when the acetylene is interrupted by two methylene groups from the sulfur atom as seen for the carbon shifts of compound 6.The shifts of C-9 (17.99),C-10 (78.98),C-10 (81.07) and C-12 (18.77) are very close to the calculated shifts of these carbon nuclei.Bus et al. 16 have reported 80.20 ppm as the basic value for an unperturbed acetylenic carbon atom in a long chain fatty acid ester.They have also reported the shift effect of the methoxycarbonyl group on the acetylenic carbon atoms at different positions (C2/C3 to C11/C12) from the methoxycarbonyl group, while the terminal methyl group was reported not to have any effect on the acetylenic carbon atoms beyond the ω-3 position.From their report, the shift effects of the methoxycarbonyl group on the chemical shift of the acetylenic center located between positions 8 and 12 from the methoxycarbonyl group in a long chain fatty ester are as follows:

Position
Shift effect of COOMe Assuming that the additivity rule employed for the calculation of the shift of the methylene carbon atoms is valid for the acetylenic group, the shift effect of a sulphur atom on an acetylene carbon atom can be deduced by subtracting the basic value (80.20 ppm) and the combined shift effects due to the methoxycarbonyl group and terminal methyl, from the observed chemical shift value for such acetylenic carbon.The results of this calculation are presented in Table 4 for the positional isomers of methyl 6-thia-octadecynoate (5-8).
These results show that the sulphur atom consistently exerts a shielding effect on the acetylenic carbon atom proximal to it and a deshielding effect on the carbon remote from it.and chemical shifts obtained relative to tetramethylsilane as an internal standard.Gas-liquid chromatographic (GLC) analyses were carried out on a Hewlett Packard HP5890 gas chromatograph fitted with a 30 m capillary column (0.25 mm internal diameter, 0.25 µm film thickness, SPB-1 or 0.53 mm internal diameter, 0.20 µm film thickness, SP-2380).Helium (2 ml/min) was used as the carrier gas under isothermal conditions (240 o C or 180 o C on SPB-1 and 120 o C, 160 o C or 190 o C on SP-2380) with a flame ionization detector.Gas chromatography-mass spectrometric (GC-MS) analyses were carried out on a Hewlettt Packard HP5890 gas chromatograph fitted with a capillary glass column (12 m x 0.2 mm i.d.), coated with crosslinked methyl silicone gum (HP.1, 0.33 µm film thickness).The compounds were submitted to on column injection at 140 o C for 3 min, then temperature programmed at 5 o C min - 1 to 250 o C using helium as the carrier gas.The column outlet was connected to a Hewlett Packard HP5970 series mass selective detector, operating at an ionization energy of 70eV.Microanalysis was performed on Perkin Elmer PE 2400 series II CHNS/O analyzer.All chemicals and reagents were of analytical reagent grade.

Table 4 .
Chemical shift effects due to a sulphur atom on the acetylenic carbon atoms in positional isomers of methyl 6-thia-octadecynoate (5-8) Thin layer chromatographic (TLC) analyses were performed on microscopic glass plates coated with normal silica gel type 60 (about 0.1 mm layers, E. Merck no.7730).Preparative TLC separations were carried out on glass plates (20 x 20 cm) coated with silica gel GF254 type 60 (0.7 mm layers, E. Merck no.7730).Column chromatography was performed by gradient elution on silica gel 60 (E.Merck no.7734) using mixtures of nhexane:diethyl ether as eluent.Infrared spectra were recorded on a Nicolet 20SXC-FTIR spectrophotometer or a Shimadzu model 470 infrared spectrometer and were calibrated against polystyrene absorption peak at 1601 cm -1 .Samples were run as neat films.1Hand13Cnuclear magnetic resonance (NMR) spectra were obtained on a JEOL FX 90Q (90 MHz) with proton observation at 90 MHz and carbon observation at 22.5 MHz.Samples were dissolved in CDCl 3 10octadecynoate 6 (1.503 g, 78.6%).