10-Dimethylamino Derivatives of Benzo[h]quinoline and Benzo[h]quinazolines: Fluorescent Proton Sponge Analogues with Opposedperi-NMe₂/–N═ Groups. How to Distinguish between Proton Sponges and Pseudo-Proton Sponges

Abstract

For the first time, 10-dimethylamino derivatives of benzo[h]quinoline 6 and benzo[h]quinazoline 7a-e as mixed analogues of archetypal 1,8-bis(dimethylamino)naphthalene ("proton sponge") 1 and quino[7,8-h]quinoline 2a have been examined. Similar to 1 and 2, compounds 6 and 7 display rather high basicity, forming chelated monocations. At the same time, unexpected specifics of the protonated NMe2/-N═ systems consist of a strong shift of the NH proton to the 10-NMe2 group, contrary to the "aniline-pyridine" basicity rule. In case of 4H(+), a rapid migration (in the NMR time scale) of the NH proton between two nitrogen atoms along the N-H···N hydrogen bond was registered at room temperature and frozen below -30 °C with the proton fixed on the NMe2 group. Two different approaches for classification of strong neutral nitrogen organic bases as proton sponges (kinetically inert compounds) or pseudo-proton sponges (kinetically active) are discussed. On this basis, benzoquinoline 6 was identified as staying closer to pseudo-proton sponges while 7a-e to proton sponges due to the presence in their molecules of bulky substituents in the pyrimidine ring. Other remarkable peculiarities of 6 and 7 are their yellow color and luminescence in the visible region distinguishing them from colorless 1 and 2a.

1,8-Bis(dimethylamino)naphthyl-2-ketimines: Inside vs outside protonation

“…Thus, in the case of 7b’ , the chemical shift at 3.3 ppm proves the proton transfer to the amino nitrogen, as shown in Scheme 8 for ( in,out )- 7b’ . In other words, in the case of 7b’ , steric pressure of the trimethoxyphenyl substituent facilitates the 1-NMe 2 group’s out -inversion which is stabilised by an IHB, forming N(sp 3 )/N(sp 2 ) type of proton sponges, which were recently reported in our paper [18]. It was previously shown that the in,out -conformation can be stabilised by placing the following functionalities in position 2(7): tertiary alcoholic groups which are able to form the O–H···N IHB [16–17 19], bulky substituents rendering a steric pressure onto the 1-NMe 2 group [7,20], or a metal atom coordinating the NMe 2 group as a ligand causing its inversion [21] (Scheme 9).…”

Proton‐Sponge‐Like Superbases Built on the Benzo[h]quinoline Platform

“…[16] Thus, the data obtained clearly demonstrates that the transformation aminoquinoline 7 → quinolinol 13 is governed not only by the amount of positive charge on the ipso-carbon atom and the presence of additional electrophilic centres. [6] This opinion is confirmed by the X-ray structure of 6·HBF 4 (Figure 2), which reveals quite a short distance between the NH proton and the BF 4 anion in 6·HBF 4 (2.58 Å), notably shorter than that in 2·HBF 4 (2.91 Å). [17] Next, we measured the pK a values of 6 and 7 in [D 6 ]DMSO by a competitive method using NMR monitoring.…”

“…Other factors may be at play, for example, the reduced aromaticity of the central ring and the enhanced reactivity of the so-called K-region in phenanthrene and its derivatives (e.g., elevated doublebond character of the C5-C6 bond in 7) leading to a more stable σ adduct. [6,20] At the same time, all four components of the mixture depicted in Figure S28 are observed in their own spectral regions as though four spectra were superimposed. [18] The transprotonation experiments with equimolar amounts of proton sponge 2 as the reference compound and mono-protonated bases 6·HBF 4 and 7·HBF 4 , respectively, were successfully completed to give the data depicted in Figures S27 and S28 in the Supporting Information.…”

“…Further reaction with potassium hydroxide during standard work up did not affect the ratio of reaction products 7 and 13. [6,19] Thus, benzoquinolines 6 and 7 turn out to be at the extremes when considering the basicities of the parent compounds 2 and 3 (Scheme 6), and the strategy of annulating a pyridine ring to 1 proved to be quite successful in terms of basicity enhancement (transition 1 → 6 gains 6.3 pK a units!) The model experiments with proton sponges 2 and 15 did not yield any results (the starting materials remained unchanged at reflux in both 2 % as well as 15 % H 2 SO 4 ) although the mono-nitrated proton sponge 15 was able to exchange one of its NMe 2 groups with a hydroxy to give naphthol 16 under the action of alkali.…”

“…[6,7] This makes molecules with the neighbouring NAlk 2 and Py fragments quite rare, in spite of their interesting photophysical, charge-transfer and proton-transfer properties. Their principal difference is in the key fragment that appears first: either the pyridine ring (as in amine 4) or the dimethylamino group (as in peri-diamine 5, Scheme 1).…”