Utilization of Stearic acid Extracted from Olive Pomace for Production of Triazoles, Thiadiazoles and Thiadiazines Derivatives of Potential Biological Activities.

Abstract

Olive Pomace was firstly dried, then pomace olive oil was extracted, and the obtained oil was hydrolyzed to produce glycerol and mixture of fatty acids. Fatty acids mixture was separated, this mixture was then cooled, where the all saturated fatty acids were solidified, and then they were filtered off. These saturated fatty acids were identified by GC mass after esterification, and were identified as stearic, palmitic and myristic acids. Stearic acid was extracted using supercritical CO2 extractor. The stearic acid was confirmed by means of GC mass after its esterification, and it was used as starting material for preparation of a variety of heterocyclic compounds, which were then tested for their antimicrobial activities. Thus the long-chain fatty acid hydrazide (2) was prepared from the corresponding long-chain fatty ester with hydrazine hydrate. Reacting 2 with phenyl isothiocyanate afforded the corresponding thiosemicarbazide 4. The later 4 underwent intramolecular cyclization in basic medium, and gave the s-triazole derivative 5, which was methylated and afforded 3-heptadecanyl-5-(methylthio)-4-phenyl-4H-1,3,4-triazole (7), which was then treated with hydrazine hydrate and afforded the corresponding 1-(5-heptadecanyl-4-phenyl-4H-1,2,4-triazol-3-yl) hydrazine (8).On the other hand, thiosemicarbazide 4 underwent intramolecular cyclization in acid medium and afforded the corresponding thiadiazole derivative 6.Treatment of thiosemicarbazide 4 with ethyl chloro(arylhydrazono) acetate derivatives 9a-b, furnished a single product 13 (Scheme 6). Similarly, when the thiosemicarbazide 4 was treated with the phenylcarbamoylarylhydrazonyl chloride 10a-c, it afforded (3-Aryl-N-5-(phenylcarbamoyl)-1,3,4-thiadiazol-2(3H)-ylidene)octadecanehydrazide 15a-c (Scheme 7). Also the reaction of thiosemicarbazide 4 with 2-oxo-N-arylpropanehydrazonoyl chlorides 11a-c and N-phenylbenzohydrazonoyl chloride 11d gave the corresponding thiadiazole derivatives 16a-d as shown in Scheme 8. A solution of thiosemicarbazide 4 was treated with the haloketones 17a-c, afforded the thiadiazine derivatives 20a-c, as shown in Scheme 9. Analogously, the thiosemicarbazide 4 was reacted with α-haloketones 21a-b and afforded the corresponding products 22a-b (Scheme 9). The structure elucidation of all synthesized compounds is based on the elemental analysis and spectral data (IR, 1H NMR, 13C NMR and MS).