M.L. Izquierdo

Azinium-N-(2′-azinyl)aminides: synthesis, structure and reactivity

Abstract Several azinium-N-(2′-azinyl)aminides are reported. The structure of pyridinium-N-(2′-pyridyl)aminide has been studied, both in solution and in crystalline state, and results have been compared. In non-polar solvents, the aminides present a planar conformation stabilized by an intramolecular hydrogen bond. The reactivity toward electrophiles confirms the structural data, producing either N- or C- substitutions under mild conditions.

Conformational study of N-substituted 8-azabicyclo[3.2.1]octan-3-ones

Abstract N-Substituted 8-azabicyclo[3.2.1]octan-3-ones have been studied by 1H and 13C NMR spectroscopy. In CDCl3 solutions, these ketones display the same preferred conformation. The pyrrolidine and piperidone rings adopt a flattened N-8 envelope and distorted chair conformation, puckered at N-8 and flattened at C-3, respectively, with the N-substituent in axial position with respect to the piperidone ring.

Pyridinium-N-(2-pyridyl)aminides : a selective approach to substituted 2-aminopyridines

Abstract Differently substituted 2-aminopyridines have been prepared in two steps from pyridinium-N-(2-pyridyl)aminide, by reaction with the corresponding elect

Synthesis and structural and conformational study of some esters derived from 3,7-dimethyl-3,7-diazabicyclo [3.3.1.] nonan-9-ol

Abstract A series of 9-acyloxy-3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonanes have been synthesized and studied by 1H- and 13C-NMR spectroscopy. In CDCl3 solution, these compounds adopt an almost perfect chair-chair conformation with the N-substituents in equatorial position. By comparing the NMR parameters of these compounds with those of some aza and diaza bi- and tri-cyclane derivatives, several stereoelectronic effects have been deduced.

Synthesis and structural, conformational and pharmacological study of N-β(or γ)acyloxyalkylnortropinones

A series of N-β(or γ)acyloxyalkylnortropinones was synthesized and studied by 1H and 13C NMR spectroscopies, and the crystal structure of N-[β-(diphenylacetyloxy)ethyl] nortropinone 1 was determined by X-ray diffraction. In CDCl3 solution, the compounds studied display the same preferred conformation. The pyrrolidine and piperidone rings adopt a flattened N8 envelope and distorted chair conformation, puckered at N8 and flattened at C3, respectively, with the N-substituent in the axial position with respect to the piperidone ring. The ability of the title compounds to antagonize the histamine and acetylcholine-induced contraction of guinea pig ileum is also reported. An initial structure-activity relationship is proposed.

Heterosryl Stabilised Azinium Yields. 1,3,4-Thiadiazole as Stabilising Group

Reaction of 1-[(1,3,5-thiadiazol-2-yl)]-methylpyridinium derivatives with diverse electrophiles produced disubstituted heteroarylmethylpyridinium ylides. Only with phenyl isothiocyanate 1,3-dipolar cycloaddition was observed

Synthesis and structural and conformational study of 3α-methoxycarbonyl-3β-(3′,4′,5′-trimethoxybenzamido)-N8-substituted nortropanes

Abstract Two 3α-methoxycarbonyl-3β-(3′,4′,5′-trimethoxybenzamido)-N8-substituted nortropanes have been synthesized and studied by IR, 1 H and 13 C NMR spectroscopy and the crystal structure of 3α-methoxycarbonyl-3β-(3′,4′,5′,-trimethoxybenzamido) tropane (IIa) has been determined by X-ray diffraction. The compounds studied display in deuterochloroform the same preferred conformation. The pyrrolidine and piperidine rings adopt a flattened N8 envelope and distorted chair conformation, puckered at N8 and markedly flattened at C3, with the N-substituent in equatorial position. This conformation seems to be governed by an intramolecular hydrogen bond. The crystal structure of IIa shows a complex hydrogen bonding network. Concerning the tropane skeleton, the X-ray results for IIa are quite similar to those found for compounds IIa,b in CDCl 3 solution. Some spectroscopy data of the precursor amidonitriles are also described.

Structural and conformational study of some N′-substituted benzoyl derivatives of the 3-β-amino-3-α-carbamoyl-N-8-substituted nortropanes

Abstract A series of substituted benzoyl derivatives of 3-β-amino-3-α-carbamoyl- N -8-substituted nortropanes has been synthesized and studied by IR, 1 H and 13 NMR spectroscopy, and the crystal structure of 3-α-carbamoyl-3-β- p -Chlorobenzamidotropane ( VIb ) has been determined by X-ray diffraction. The compounds studied display in deuterochloroform and deuteromethanol a chair-envelope conformation markedly flattened at C3 with the benzamido and carbamoyl groups in pseudo-equatorial and pseudo-axial positions respectively.

Structural and conformational study of some N'-p-halobenzoyl derivatives of the 3β-amino-3α-methoxycarbonyl(or cyano)-N8-substituted nortropanes

Abstract A series of N ′- p -F(or Cl)-benzoyl derivatives of 3β-amino-3α-methoxycarbonyl(or cyano)- N 8-substituted nortropanes has been synthesized and studied by IR, 1 H and 13 C NMR spectroscopy, and the crystal structure of 3α-methoxycarbonyl-3β- p -chlorobenzamido-tropane ( VIb ) has been determined by X-ray diffraction. The compounds studied display, in deuterochloroform, a chair envelope conformation very flattened at C3 and puckered at N8, with the benzamido and methoxycarbonyl groups in pseudo-equatorial and pseudo-axial positions respectively. In this solvent, intramolecular hydrogen bondings are observed. As regards the bicyclic system, results are in close agreement with those found for compound VIb in the crystalline state.

Synthesis and structural, conformational and pharmacological study of some esters derived from 3-β-hydroxytropan-3-α-carboxylic acid

Abstract A series of 3-β-hydroxy-3-α-alkoxycarbonyl tropanes has been synthesized and studied by IR, 1 H and 13 C NMR spectroscopy, and the crystal structure of ethyl-3-β-hydroxytropan-3-α-carboxylate ( VIb ) and phenethyl-3-β-hydroxytropan-3-α-carboxylate ( VIc ) have been determined by X-ray diffraction. The compounds studied display in chloroform- d the same preferred conformation. The pyrrolidine and piperidine rings adopt a flattened N8 envelope and a distorted chair conformation puckered at N8 and strongly flattened at C3, respectively, with the N -methyl and hydroxy groups in equatorial and pseudo-equatorial positions and the ester group in a pseudo-axial arrangement with respect to the piperidine ring. An intramolecular interaction between the hydroxy group and the nitrogen atom is proposed. However in CD 3 OD solution the intramolecular hydrogen bond is broken and the hydroxy and ester groups adopt a different relative disposition, more sterically favourable, decreasing the flattening of the piperidine ring. With regard to the tropane skeleton, these results are in close agreement with those found for compounds VIb and VIc in the crystalline state. The inhibitory effect of the title compounds on 3 H-GABA binding to a synaptosomal brain membranes is also reported.