Some Miscellaneous Fatty Acids

Fatty compounds with various functional groups of combinations thereof have been reported or synthesized. The following is a somewhat arbitrary selection of the ¹H-NMR data of such compounds.

Lactones

Fatty lactones such as δ- and γ-stearolactone can be obtained from oleic acid by reaction with mineral acids. The following data were given for the characteristic shifts of these lactones (Cermak and Isbell, 2000): For δ-stearolactone, a multiplet at 4.22-4.25 ppm was assigned to the methine proton at the junction of the alkyl chain and the lactone ring; two separate multiplets at 2.51-2.57 and 2.41-2.44 ppm were caused by one proton each of the methylene adjacent to the carbonyl group, a multiplet caused by three protons, one attached to the carbon α to the methine and two protons on the β carbon (middle carbon of the δ-lactone ring), a multiplet at 1.64-1.71 ppm caused by the second proton on the α carbon and finally another multiplet at 1.47-1.55 ppm caused by the four methylene protons in the fatty acid chain adjacent to the junction methine. The multiplet of methine proton in γ-stearolactone was observed at 4.38-4.43 ppm while the two protons α to the cabonyl group were observed as a broad multiplet at 2.39-2.48 ppm with the two protons of the carbon α to the methine observed as individual multiplets at 2.27-2.28 and 1.81-1.83 ppm. The two protons α to the carbonyl also each caused a multiplet, one at 1.62-1.69 ppm and the other at 1.47-1.56 ppm. Similar data were given for δ- and γ-eicosanolactone (Isbell and Kleiman 1996). Adding a halogen in 6-chloro-δ-eicosanolactone gave a multiplet at 3.91 ppm due to the proton at C-6 (Mund and Isbell, 1999). In 6-hydroxy-δ-eicosanolactone, a multiplet at 3.48-3.57 ppm due to the proton at C-6 is observed (Frykman and Isbell, 1997). An additional epoxy group in 6-hydroxy-13,14-epoxy-δ-docosanolactone generated a multiplet at 2.89-2.82 ppm (Frykman and Isbell, 1997).

Mixed Oxygenated Groups

Epoxy/hydroxy. A diastereomeric mixture of the methyl ester of epoxidized ricinoleic acid (cis-9,10-epoxy-12(R)-hydroxyoctadecanoate) displayed multiplets at 2.80 and 3.01 for the protons at C10 and C9, respectively, as well as 3.70-3.74 ppm for the proton at C-12 (hydroxy-bearing carbon) (Fürmeier and Metzger, 2003a). Other authors (Foglia et al., 1998) reported the shifts of the protons at C-9 and C-10 together as a broad multiplet at 2.9 ppm and the proton at C-12 generating a multiplet 3.09 ppm.

Hydroxy/keto. In fatty compounds with the β-hydroxy keto groups (1-ol-3-ones), the signal of the proton on the hydroxy-bearing carbon was observed as a broad multiplet at 4.00 ppm and the signal of the protons attached to the carbon in the 2-position of this moiety was split, generating two sets of doublets of doublets, one at 2.58 and one at 2.47 ppm (Kenar, 2002). The protons α to the carbonyl group caused a triplet at 2.40 ppm. When separating the two oxygenated functionalities by an additional CH₂ to give moieties of the type 1-ol-4-ones, in methyl 12-hydroxy-9-oxostearate the two separating methylenes were observed as a multiplet at 2.4-2.6 ppm and the proton attached to the hydroxy-bearing carbon also caused a multiplet at 3.4-3.6 ppm (Lie Ken Jie and Lam, 1996). The same shifts were reported when "switching" the oxo and hydroxy groups (Lie Ken Jie and Lam, 1996).

In methyl 7-hydroxy-17-oxo-9(Z)-octadecenoate with CD₃OD as solvent, signals at 3.49 ppm (H-7), 2.19 ppm (H-8), and 5.39 as well as 5.54 ppm (H-9 and H-10) were observed (patterns not given) (Lanser and Manthey, 1999). The oxo group induced a strong downfield shift on the resonance of the terminal methyl group to 2.12 ppm, while the signal of the C16 protons was found at 2.40 ppm.

Epoxy/keto. Epoxy dioxo compounds of the type 2,3-epoxy-1,4-diones have been reported (Lie Ken Jie et al., 1997). In methyl 10,11Z-epoxy-9,12-dioxooctadecenoate, the epoxy protons at C10 and C11 were observed as a singlet at 3.72 ppm and the protons α to the epoxydione moiety resonated as a multiplet at 2.49-2.70 ppm. These shifts were observed at 3.56 ppm and 2.34-2.52 ppm in the corresponding E isomer.

Alkoxy compounds. In methyl esters of acids with terminal branching and a methoxy group at C2, the signal of C2 was observed together with the methyl ester singlet at about 3.75 ppm while the methoxy protons gave rise to a singlet at 3.37-3.38 ppm (Carballeira et al., 2002). In methyl 5-methoxyeicosanoate, the methoxy protons caused a singlet at 3.29 ppm while the single proton at C5 was observed as quintet at 3.12 ppm (Isbell and Mund, 1998). In butyl 5-butoxyeicosanoate, the two protons of the α carbon of the butoxy group generated a multiplet at 3.38 ppm with the C5 proton gave rise to a multiplet at 3.18 ppm. In 2-ethylhexyl 5-(2-ethylhexoxy)-eicosanoate, the protons at the α carbon of the ethylhexoxy group were found as a multiplet at 3.97 ppm and the C5 proton as a multiplet at 3.17 ppm. Related data for such compounds include a triplet at 3.37 ppm and a quintet at 3.18 ppm in decyl 5-decyloxyeicosanoate and the same peak patterns at 3.37 ppm and 3.24 ppm in oleyl 5-oleyloxyeicosanoate (Isbell and Mund, 1998).

Chloroalkoxy compounds. In a mixture of the positional isomers of 5,6-chloromethoxy eicosanoic acid, the methoxy protons caused a singlet at 3.40 ppm, while the single protons at the 5 and 6 positions were observed at 3.96 ppm (chloro substituent) and 3.25 ppm (methoxy substituent) (Mund and Isbell, 1999), a value similar to the alkoxy compounds discussed above. For the positional isomers of 5,6-chlorobutoxy eicosanoic acid, the characteristic shifts were observed as multiplets at 3.49 ppm for the α protons of the butoxy substituent and 3.95 ppm (chloro substituent) as well as 3.33 ppm (butoxy substituent) for the protons at C5 and C6. When alkoxy was 2-propoxy, these values were 3.90, 3.64 and 3.32 with an additional signal for the propoxy methyl protons observed at 1.14 ppm. Similar values for the positional isomers of 13,14-chloroalkoxy docosanoic acids as well as 5,6-chloroalkoxy-13,14 chloroalkoxy docosanoic acids have been reported (Mund and Isbell, 1999).

Other compounds. In 10-azido-12-oxo-octadecanoate, the characteristic shifts were observed as a triplet at 2.43 ppm for the protons at C-13, a doublet of doublets at 2.56 for the protons at C-11 and a multiplet at 3.8 ppm for the C-10 proton (Lie Ken Jie and Syed-Rahmatullah, 1992). In 12(R)-azido-(13R)-hydroxy-9(Z)-octadecenoate, the protons at C12 and C13 gave rise to multiplets at 3.25 and 3.55 ppm, respectively, the C11 methylene caused a triplet at 2.43 ppm, and the double bond protons were observed as multiplets at 5.41 ppm (C10) and 5.54 ppm (C9) (Fürmeier and Metzger, 2003a). In methyl 9-azido-12-oxo-10(E)-octadecenoate, the proton at C-9 was observed as a quartet at 3.98 ppm, the double bond protons were found relatively far downfield as a doublet at 6.29 ppm (H-11) and doublet of doublets at 6.58 ppm (H-10) while the protons at C-13 resonated at 2.56 ppm as a triplet (Fürmeier and Metzger, 2003a). In the saturated form and with "switched" functional groups (methyl 12-azido-9-oxostearate), the proton on the azido-carrying carbon generated a multiplet at 3.35 ppm, and the methylene protons α to the azido carbon gave rise to signals at 2.41 (H-8) and 2.54 (H-10) ppm (Lie Ken Jie and Lam, 1996).

In 9- and 12-phenylstearates, the proton at the phenyl-bearing carbon is observed as a multiplet at 2.45 ppm (Black and Gunstone, 1996). The protons of the carbons α to the functional group cause a multiplet at 1.60 ppm.

Compounds with Halogens

The vicinal bromohydroxy derivatives of methyl oleate and oleic acid were characterized by its signals at 3.40 ppm (td, J = 3.51 and 6.24 Hz, 1H, H-C-OH) and 4.00 ppm (dt, J = 8.19 and 4.29 Hz for oleate as well as 8.97 and 3.7 for acid, 1H, H-C-Br) (Eren and Küsefoğlu, 2004). In 6-chloro-5-hydroxy eicosanoic acid, characteristic shifts were multiplets at 3.88 ppm and 3.62 ppm caused by the single protons at C6 and C5, respectively (Mund and Isbell, 1999). Corresponding values for 5-hydroxy-6-chloro eicosanoic acid are 3.90 and 3.62 ppm. The positional isomers of 13,14-chlorohydroxy docosanoic acid gave similar values (Mund and Isbell, 1999).

Methyl 9,10–dibromo-12-hydroxyoctadecanoate gave rise to a multiplet at 3.8 ppm (H-12) and another multiplet at 4.6 ppm (protons at bromine-carrying carbons C-9 and C-10). (Lie Ken Jie et al., 1996).

Methyl 12-chloro-9-oxostearate was identified by a multiplet at 3.90 ppm caused by the C-12 proton, two triplets at 2.64 and 2.42 ppm caused by the protons α to the carbonyl group and a multiplet at 2.10 ppm for protons at C-11 (Lie Ken Jie and Lam, 1996).

Halo-oxo-allenic fatty esters were obtained from epoxidized methyl santalbate (methyl trans-11-octadecen-9-ynoate) (Lie Ken Jie et al., 2003). Some NMR data of these compounds and some of their precursors with one triple bond and hydroxy groups are given in Table 1.

Table 1. 1H-NMR signals in C18 halo-hydroxy-yne and halo-oxo-allenic fatty esters (Lie Ken Jie et al., 2003)
—C≡C— or —C=C=C—	Halogen and oxygen	Chemical shifts
—C≡C—   (9a)	11-F, 12-OH (anti)	2.2-2.3 (m, H8); 3.72-3.85 (m, H12); 5.02 (ddt; H11)
—C≡C—   (9a)	11-F, 12-OH (syn)	2.19-2.33 (m, H2 and H8); 3.73 (m, H12); 4.89 (ddt; H11)
—C≡C—   (9a)	11-Cl, 12-OH (anti)	2.22-2.29 (m, H8); 3.7-3.8 (m, H12); 4.60 (dt; H11)
—C≡C—   (9a)	11-F, 12 C=O	2.2-2.32 (m, H8); 2.61-2.67 (m, H13); 5.28 (dt; H11)
—C≡C—   (9a)	11-Cl, 12 C=O	2.27 (m, H8); 2.68-2.87 (m, H13); 4.85 (t; H11)
—C=C=C—   (9,10)	11-F, 12 C=O	2.25-2.4 (m, H2, H8); 2.51 (t, H13); 6.34 (t; H9)
—C=C=C—   (9,10)	11-Cl, 12 C=O	2.25-2.34 (m, H8); 2.58-2.65 (m, H13); 6.01 (t; H9)

Cyclic Compounds

The characteristic shifts of methine protons in N-substituted aziridine fatty compounds (three-membered nitrogen-containing heterocycles, with the heterocycle at C9-C10 in the fatty acid chain) are in the range of 1.42-2.54 ppm. The shifts of the N-H compound are at 1.90 ppm (Fürmeier and Metzger, 2003a).

In dihydrooxazoles, the protons of the carbons carrying the heterocyclic moiety were observed as multiplets at 3.37 ppm (CHN) and 4.03 ppm (CHO) (Fürmeier and Metzger, 2003b).

Estolides

For a polyestolide derived from oleic acid, the methylene protons for the ester moiety were observed at 2.25 ppm for those adjacent to ester moieties and at 2.30 ppm for those adjacent to the acid moieties (Isbell and Kleiman, 1994). The integration values of these signals can be used for assessing the degree of polymerization. The key methine protons produced their signal at 4.84 ppm.

Similar shifts have been reported for other estolides (Cermak and Isbell, 2001).

Literature:

• Black, K.D. and Gunstone, F.D. The Friedel-Crafts adducts of methyl oleate with benzene and toluene. Chem. Phys. Lipids, 79, 87-94 (1996).
• Carballeira, N.M., Cruz, H. and Ayala, N.L. Total synthesis of 2-methoxy-14-methylpentadecanoic acid and the novel 2-methoxy-14-methylhexadecanoic acid identified in the sponge Agelas dispar. Lipids, 37, 1033-1037 (2002).
• Cermak, S.C. and Isbell, T.A. Synthesis of δ-stearolactone from oleic acid. J. Am. Oil Chem. Soc., 77, 243-248 (2000).
• Cermak, S.C. and Isbell, T.A. Synthesis of estolides from oleic and saturated fatty acids. J. Am. Oil Chem. Soc., 78, 557-565 (2001).
• Eren, T. and Küsefoğlu, S.H. One-step hydroxybromination of fatty acid derivatives. Eur. J. Lipid Sci. Technol., 106, 27-34 (2004).
• Foglia, T.A., Sonnet, P.E., Nunez, A. and Dudley, R.L. Selective oxidations of methyl ricinoleate: diastereoselective epoxidation with titanium^IV catalysts. J. Am. Oil Chem. Soc., 75, 601-607 (1998).
• Frykman, H.B. and Isbell, T.A. Synthesis of 6-hydroxy δ-lactones and 5,6-dihydroxy eicosanoic/docosanoic acids from meadowfoam fatty acids via a lipase-mediated self-epoxidation. J. Am. Oil Chem. Soc., 74, 719-722 (1997).
• Fürmeier, S. and Metzger, J.O. Fat-derived aziridines and their N-substituted derivatives: biologically active compounds based on renewable raw materials. Eur. J. Org. Chem., 649-659 (2003a).
• Fürmeier, S. and Metzger, J.O. Synthesis of new heterocyclic fatty compounds. Eur. J. Org. Chem., 885-893 (2003b).
• Isbell, T.A. and Kleiman, R. Characterization of estolides from the acid-catalyzed condensation of oleic acid. J. Am. Oil Chem. Soc., 71, 379-383 (1994).
• Isbell, T.A. and Kleiman, R. Mineral acid-catalyzed condensation of meadowfoam fatty acids into estolides. J. Am. Oil Chem. Soc., 73, 1097-1107 (1996).
• Isbell, T.A. and Mund, M.S. Synthesis of secondary ethers derived from meadowfoam oil. J. Am. Oil Chem. Soc., 75, 1021-1029 (1998).
• Kenar, J.A. Reduction of fatty ester Δ2-isoxazoline heterocycles. Preparation of fatty esters containing the β-hydroxy ketone moiety. J. Am. Oil Chem. Soc., 79, 351-356 (2002).
• Lanser, A.C. and Manthey, L.K. Bioconversion of oleic acid by Bacillus strain NRRL BD-447: Identification of 7-hydroxy-17-oxo-9-cis-octadecenoic acid. J. Am. Oil Chem. Soc., 76, 1023-1026 (1999).
• Lie Ken Jie, M.S.F. and Alam, M.S. Novel azido fatty acid ester derivatives from conjugated C₁₈ enynoate. Chem. Phys. Lipids, 111, 29-35 (2001).
• Lie Ken Jie, M.S.F. and Lam, C.K. Regiospecific oxidation of unsaturated fatty esters with palladium (ii) chloride/p-benzoquinone: a sonochemical approach. Chem. Phys. Lipids, 81, 55-61 (1996).
• Lie Ken Jie, M.S.F. and Syed-Rahmatullah, M.S.K. Synthesis and spectroscopic properties of long-chain aza, aziridine azetidine fatty esters. J. Am. Oil Chem. Soc., 69, 359-362 (1992).
• Lie Ken Jie, M.S.F., Lau, M.M.L., Lam, C.N.W., Alam, M.S., Metzger, J.O. and Biermann U. Novel halo-oxo-allenic fatty ester derivatives from epoxidized methyl santalbate (methyl trans-11-octadecyn-9-ynoate). Chem. Phys. Lipids, 125, 93-101 (2003).
• Lie Ken Jie, M.S.F., Pasha, M.K. and Ahmad, F. Ultrasound-assisted synthesis of santalbic acid and a study of triacylglycerol species in Santalum album (Linn.) seed oil. Lipids, 31, 1083-1089 (1996).
• Lie Ken Jie, M.S.F., Pasha, M.K. and Lam, C.K. Ultrasonically stimulated oxidation reactions of 2,5-disubstituted C₁₈ furanoid fatty ester. Chem. Phys. Lipids, 85, 101-106 (1997).
• Mund, M.S. and Isbell, T.A. Synthesis of chloroalkoxy eicosanoic and docosanoic acids from meadowfoam fatty acids by oxidation with aqueous sodium hypochlorite. J. Am. Oil Chem. Soc., 76, 1189-1200 (1999).