Self-assembly of amides of endo-3-(3-methylthio-1H-1,2,4-triazol-5-yl)bicyclo[2.2.1]hept-5-ene-2-carboxylic acid directed by N-amide substituents

Abstract

The condensation of endo-S-methyl-N 0 -(bicyclo[2.2.1]hept-5-ene-2,3-dicarbonyl) isothiosemicarbazide with 12 primary amines was investigated. The molecular structure of all new products (3a-3l) was confirmed by spectroscopic methods, including 1D/2D NMR, IR spectroscopy and mass spectrometry, and an X-ray crystallography of three selected representative amide crystals. The 2,3-disubstitution of norbornene (endo-bicyclo[2.2.1]hept-5-ene) unit stabilizes overall cisoid orientation of substituents. Spectroscopic and structural analyses indicate that for the series of 12 derivatives the rigid molecular part is endo-bicyclo[2.2.1]hept-5-ene-2-carboxamide fragment. The specific orientation of the 3-(methylthio)-1H-1,2, 4-triazole unit, second substituent to the norbornene skeleton, is correlated with the chemical character of N-amide substituents. Phenyl derivatives stabilize transoid orientation of the N-H triazole and C=O amide bonds, whereas the alkyl (methylene or methine) spacer promotes cisoid orientation of these bonds and provides possibility for an intramolecular hydrogen bonding. The solid-state IR spectra and X-ray analysis indicate three patterns of intermolecular association in this series of crystals. Hydrogen bonds observed in crystals influence positions of vibrational bands corresponding to m NH (3322-3180 cm -1 ), m C=O (1634-1676 cm -1 ), and d NH (1600-1500 cm -1 ).

New Norcantharidin Analogs: Synthesis and Anticancer Activity

“…The synthetic route for the synthesis of N ‐substituted amides of 3‐(3‐ethylthio‐1,2,4‐triazol‐5‐yl)‐7‐oxabicyclo‐[2.2.1]heptane‐2‐carboxylic acid ( 2–12 ) is presented in Scheme . S‐ Ethyl‐ N ‐(7‐oxabicyclo‐[2.2.1]heptane‐2,3‐dicarbonyl)isothiosemicarbazide ( 1 ) used as the starting material was obtained by condensation reaction of exo ‐7‐oxabicyclo‐[2.2.1]heptane‐2,3‐dicarboxylic acid anhydride with S ‐ethyl isothiosemicarbazide hydrobromide in boiling glacial acetic acid . Next, the initial, cyclic isothiosemicarbazide was heated with selected primary aliphatic and aromatic amines in the boiling glacial acetic acid.…”

“…In this reaction, amines as nitrogen nucleophiles opened the imide ring and intermediate compounds with two linear amide groups were obtained . Then probably spontaneous cyclization of S ‐ethyl‐ N 1 ‐(carbonyl)isothiosemicarbazide chain (longer linear chain) due to the elimination of molecule of water took place producing 1,2,4‐triazole system and new N ‐substituted amides of 3‐(3‐ethylthio‐1,2,4‐triazol‐5‐yl)‐7‐oxabicyclo‐[2.2.1]heptane‐2‐carboxylic acid were obtained. The reaction proceeded in one step without isolation of intermediate.…”

Biological Activity of Novel N-Substituted Amides of endo-3-(3-Methylthio-1,2,4-triazol-5-yl)bicyclo[2.2.1]hept-5-ene-2-carboxylic Acid and N-Substituted Amides of 1-(5-Methylthio-1,2,4-triazol-3-yl)cyclohexane-2-carboxylic Acids

“…The starting endo-S-methyl-N 1 -(bicyclo[2.2.1]hept-5-ene-2,3-dicarbonyl)isothiosemicarbazide and S-methyl-N 1 -(cyclohexane-2,3-dicarbonyl)iso thi osemicarbazide, used in this study, were obtained by the direct condensation of S-methyl isothiosemicarbazide hydroiodide with a suitable dicarboxylic acid anhydride. The N-substituted amides were prepared by the condensation of the abovementioned isothiosemicarbazides with aliphatic and aromatic primary amines in boiling glacial acetic acid (Mendyk et al, 2011;Galewicz-Walesa and Pachuta-Stec, 2003). The chemical structures of the obtained and examined compounds are presented in Fig.…”

“…Prompted by these reports, and in continuation of our search for bioactive molecules (Pitucha et al, , 2010, it seemed worthwhile to synthesize derivatives of 1,2,4-triazole, containing the amide and methylthio group like compounds with potential biological activity (Pachuta-Stec et al, 2009). The syntheses and molecular structures have been described earlier (Mendyk et al, 2011;Galewicz-Walesa and Pachuta-Stec, 2003). Here we report the evaluation of the results of the preliminary microbiological investigation.…”

Interplay of thermochemistry and Structural Chemistry, the Journal (volume 22, 2011, issues 1–3) and the discipline

“…In the paper by Mendyk et al [63], studies on the synthesis and structure of twelve 2,3-disubstituted asymmetric derivatives of norbornene with endo-S-methyl-N 0 -(bicyclo[2.2.1]hept-5-ene-2,3-dicarbonyl) isothiosemicarbazide are reported. 1 H NMR and 13 C NMR along with IR and mass spectrometry were used to study molecular structures.…”