1,8-Bis(hexamethyltriaminophosphazenyl)naphthalene, HMPN:  A Superbasic Bisphosphazene “Proton Sponge”

Abstract

It is shown that a combination of Schwesinger's phosphazene base concept and the idea of the disubstituted 1,8-naphthalene spacer, first introduced by Alder in paradigmatic 1,8-bis(dimethylamino)naphthalene (DMAN), yields a new superbase, HMPN, which represents the up to date most basic representative of this class of "proton sponges", as evidenced by the theoretically estimated proton affinity PA = 274 kcal/mol and the measured pK(BH+) (MeCN) 29.9 +/- 0.2. HMPN is by nearly 12 orders of magnitude more basic than Alder's classical 1,8-bis(dimethylamino)naphthalene (DMAN). The title compound, HMPN, is prepared and fully characterized. The spatial structure of HMPN and its conjugate acid is determined by X-ray technique and theoretical DFT calculations. It is found that monoprotonated HMPN has an unsymmetrical intramolecular hydrogen bridge (IHB). This cooperative proton chelating effect renders the bisphosphazene more basic than Schwesinger's set of "monodentate" P1 phosphazene bases. The density functional calculations are in good accordance with the experimental results, providing some complementary information. They conclusively show that the high basicity of HMPN is a consequence of the high energy content of the base in its initial neutral state and the intramolecular hydrogen bonding in the resulting conjugate acid with contributions to proton affinity of 14.1 and 9.5 kcal/mol, respectively.

Effect of excipients on PLGA film degradation and the stability of an incorporated peptide

“…3). The initial decrease in pH was unexpected due to the high pKa of the proton sponge; however, steric hindrance of the amines has been shown to limit the rate of proton uptake by a proton sponge [26]. The proton sponge was able to maintain the film 'pH', which remained unchanged through 72hrs of storage (Fig.…”

Hydrogen Motion in Proton Sponge Cations: A Theoretical Study

“…[2][3][4][5] A proton sponge usually has two basic nitrogen atoms attached to a relatively rigid organic core. The distance between the nitrogen atoms (typically 2.75 ) allows the incoming proton to coordinate to both nitrogen atoms simultaneously.…”

“…In this case, the wave function still has a single maximum at the central position, although [ This work presents a study of intramolecular NHN hydrogen bonds in cations of the following proton sponges: 2,7-bis(trimethylsilyl)-1,8-bis(dimethylamino)naphthalene (1), 1,6-diazabicyclo [4.4.4. ]tetradecane (2), 1,9-bis(dimethylamino)dibenzoselenophene (3), 1,9-bis(dimethylamino)dibenzothiophene (4), 4,5-bis(dimethylamino)fluorene (5), quino [7,8-h]quinoline (6) 1,2-bis(dimethylamino)benzene (7), and 1,12-bis(dimethylamino)benzo[c]phenantrene (8). Three different patterns were found for proton motion: systems with a singlewell potential (cations 1-2), systems with a double-well potential and low proton transfer barrier, DE e (cations [3][4][5], and those with a double-well potential and a high barrier (cations [6][7][8].…”

First and Second Proton Affinities of Carbon Bases

“…[5] Molecules having a carbon atom carrying a lone pair should possess an even higher basicity than amines and imines. The PA of singlet ( 1 A 1 ) CH 2 is indeed slightly higher (205 kcal mol À1 ) [6] than that of NH 3 .…”