- Improved Preparation of the Clathrate Host Compound Tri-o-thymotide and Related Trisalicylide Derivatives
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In order to improve the relatively low yield (ca. 35percent) previously observed in the synthesis of tri-o-thymotide (TOT, 1) from o-thymotic acid (2), the cyclodehydration was studied using a variety of conditions.The low yield is due to the formation of di-o-thymotide (DOT, 3), previously reported, and at least three other products (4-6), which apparently result from the acid-catalyzed decarboxylation of 2 and subsequent condensation with thymol (7).Using pyridine as a solvent, side-product formation is inhibited.Under appropriate conditions, namely, neat POCl3 at 50 deg C, the yield of 1 is 93percent.Other salicylic acid derivatives also give high yields of the corresponding "trimers" under these conditions, thus providing a general, improved preparation of a family of potential clathrate host substances.
- Gnaim, Jallal M.,Green, Bernard S.,Arad-Yellin, Rina,Keehn, Philip M.
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p. 4525 - 4529
(2007/10/02)
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- SUBSTITUENT MODIFICATION IN TRI-O-THYMOTIDE AND ITS EFFECTS ON HOST GEOMETRY AND GUEST ENCLATHRATION. 1. SYNTHESIS
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A new synthesis is described for the preparation of tri-o-thymotide (1, TOT) and some TOT analogues.The methodology is based on the sequential coupling of appropriately substituted and protected salicylic acid monomers followed by cyclization of the deprotected open-chain trimers.A variety of protecting methodologies and coupling sequences are disscussed.The procedure seems generally applicable for the preparation of salicylides and has been used to prepare TOT in 25percent overall yield (for the coupling-deprotection-coupling-deprotection-cyclization sequence).In addition, two new modified TOT-analogues 9 (25percent), and 10 (14percent) were prepared in which the isopropyl group(s) ortho to the phenolic units in TOT is replaced by one (9) or two (10) ethyl groups.A third analogue 66, where the methyl group ortho to the carboxyl group is removed in one of the salicylic acid monomer units of TOT, requires only the last cyclization step for completion of its synthesis.This methodology represents an important breakthrough for the controlled preparation of selected thymotide (salicylide) trimers and allows easy access to a variety of modified thymotides (salicylides) for structural, conformational and host-guest studies.
- Harris, Thomas D.,Oruganti, Subra R.,Davis, Lawrence M.,Keehn, Philip M.,Green, Bernard S.
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p. 1519 - 1540
(2007/10/02)
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