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Current Tröger's Base Chemistry

Publisher Summary This chapter summarizes Trogers bases (TBs). It describes its historical developments, revival, synthesis and mechanism of formation, reactivity, physicochemical properties, and its uses and applications. The chapter also provides a brief discussion about pseudo-TBs. It is observed that in principle, any aromatic or heteroaromatic amine can serve as a possible precursor of TBs. TB derivatives are generally viewed as anomalous chiral substances with two nitrogen-containing stereogenic centers. TB derivatives are considered highly useful synthetic building blocks. The common properties of TBs include: biomimetic molecular recognition processes and complex interactions with important biomolecules. TBs represent chiral tectons exhibiting a wide range of applications, such as (1) the TB scaffold is used extensively for the construction of molecular receptors, (2) unique geometry of TB is extensively used in preparing macrocycles, (3) TB derivatives are also considered as hosts for cyclic urea and adenine derivatives, and (4) TB analogs promote investigations of second harmonic reflections from chiral surfaces.

Synthesis and molecular structure of heterocyclic Tröger's bases derived from C-amino heterocycles

Abstract Fourteen amino heterocycles were allowed to react in the different experimental conditions of formation of Trogers bases. Amino-azoles and -benzazoles yielded the corresponding Trogers bases while amino-azines and -benzazines failed to react. The exception was 6-aminoquinoline which yielded the corresponding Trogers base. When there are two positions of cyclisation the reaction is always regioselective. Trogers base analogues with pentagonal aromatic frameworks, 6b and 7b, have been synthesized for the first time and the X-ray molecular structure of 7b has been determined.

Complete 1H and 13C NMR Analysis of an Asymmetric Tröger's Base

The 1H and 13C NMR spectra of an asymmetric Trögers base were recorded and the corresponding signals assigned on the basis of long‐range coupling constants and 1H–13C correlations. In 1H NMR, ambiguities in the assignment of exo and endo hydrogen atoms and in the long‐range couplings between the methylene hydrogens were resolved.

Azolyl substituted Tröger's bases

Trogers bases 2, 3 and 4 containing azole rings as substituents on the aromatic moiety have been synthesized for the first time.

1H and13C NMR Studies of Heterocyclically Modified Tröger's Bases

The 1H and 13C NMR spectra of 15 modified representatives of Trögers base were recorded and the corresponding signals assigned. In 1H NMR, the appearance of the AA′BB′CC′(XX′) system, after irradiation of Hx(Hx), is deceptively simple and should not be first‐order analysed. The 13C chemical shifts and 1J(1H–13C) coupling constants are characteristic of these molecules.

1,3-Dipolar cycloaddition of azolium dicyanomethylides

1,3-Dipolar cycloaddition of azolium N-dicyanomethylides, which have an azomethine ylide structure, to acetylenic dipolarophiles affords azolopyridine derivatives. The initial cycloadduct has been isolated for the first time. Using unsymmetrical dipolarophiles, only one of the two possible regioisomers has been obtained. The orientation problem has been approached theoretically by a second-order perturbational treatment, which also gives good results in the case of the reaction of an azomethine imine, 1-ethylbenzotriazolium 3-dicyanomethylide.

Lewis Acid-Assisted Ene Cyclization of 2-Azetidinone-Tethered Enals: Synthesis of Enantiopure Carbacepham Derivatives

Diastereocontrolled Lewis acid-catalyzed preparation of enantiopure carbacepham derivatives have been developed starting from 2-azetidinone-tethered enals. The BF3.Et2O-promoted reaction of alkenylaldehydes 1 and 16 is effective as carbocyclization protocol to afford 4-substituted 5-hydroxycarbacephams or 3-substituted 4,5-dihydroxycarbacephams, respectively, by a type I carbonyl-ene reaction, while the BF3.Et2O or SnCl4-mediated type II carbonyl-ene cyclization of alkenylaldehydes 2 furnishes 3-methylene 5-hydroxycarbacephams along with the corresponding 3-halo 5-hydroxycarbacepham. The stereochemical outcome of these carbonyl-ene cyclizations leading to carbacepham derivatives can be explained in terms of six-membered, cyclic chair-like transition-state models. The formation of halocarbacepham derivatives is proposed to proceed by a stepwise mechanism.

A new heterocyclic rearrangement: conversion of 2-vinylpyrazolium salts into 1,2-dihydropyrimidines

Abstract Treatment of 2-vinylpyrazolium salt 1 in basic medium yields the 1,2-dihydropyrimidine 2 . The structure of 2 was established by analytical and spectroscopic methods.

Pyrimidinium N-dicyanomethylide, synthesis and reactivity towards dimethyl acetylenedicarboxylate

Par cycloaddition dipolaire 1,3 entre les composes du titre, on obtient 2 regioisomeres: cyano-6 dimethoxycarbonyl-7,8 pyrrolo [1,2-a] pyrimidines et cyano-7 dimethoxycarbonyl-5,6 pyrrolo [1,2-c] pyrimidines. Calculs MINDO/2

FT-IR and 13C-NMR Correlations for Some N-Substituted Azoles and Benzazoles

The FT-IR (in carbon tetrachloride) and 13C-NMR (in deuterochloroform) spectra of six p-substituted aniline derivatives, as reference compounds, and nine 1-p-aminophenyl-azoles and benzazoles were recorded. The measured spectral parameters from FT-IR were symmetric, vs(NH2), and antisymmetric, vas(NH2), stretching fundamentals and their band intensity ratio, A(vas)/A(vs), while the corresponding 13C-NMR parameters were C-1 to C-4 chemical shifts of 1-p-aminophenyl carbons. Different IR and 13C-NMR spectral parameters and Hammett constants σp (or σp-) were correlated, and statistic analysis of the results permitted an estimation of σp values of the nine (azol-1-yl) substituents. An empirical equation to calculate the Hammett constants of new azoles and benzazoles is proposed.