Sterically Congested Molecules, 12. Acidity Constants of Sterically Shielded Protonated Imines in Hydroxylic Solvents

Abstract

NMR spectra in combination with pH measurements are shown to provide a simple and convenient procedure for determining the basicities of imines which are either slowly hydrolyzed (4, 5) or completely stable but inconveniently weak bases (11-13). The method has the advantage that it does not require any precise knowledge of the concentrations of the substrates or reagents. N-Alkyl (4, 15) and N-unsubstituted imines (5, 8, 9, 14) show quite similar basicities with a weak solvent dependence (from pure water to 99.5% methanol) which is akin to that of pyridine. The N-aryl imines 10-13 are less basic by ca. 4 pK units. It is concluded that spatial solvent exclusion by bulky substituents has remarkably little effect on the pKL values.Protonated pyridine (pK, = 5.14) is a slightly weaker acid than protonated aniline (4.62) in water whereas the order is reversed (5.37r2] versus 5.80r31) in anhydrous methanol; minimal pK, values for pyridinium (3.6r4]) and anilinium (4.0[3,51) were reported in aqueous (ca. 20:80) methanol. These rather modest pK, variations contrast with the strong solvent-dependence for an uncharged acid like acetic acid (4.76r6l in water, but 9. 61' 1 in methanol). In the aprotic but very polar media DMSO and acetonitrile the cations pyridinium (pK, = 3.4[','] and ca. 12.4[9-111, respectively) and anilinium (3.6['.91 and 10.6[93L01) are much more acidic than acetic acid ( 12.4['~'0] and 22.3r91). This trend continues into the gas phase [I2] where the acidity difference from acetic acid grows to 125 kcal/mol for pyridinium and 136 kcalhol for anilinium, corresponding to roughly 100 pK units. Obviously, solvation of the carboxylate anion is a more critical factor[s] and actually best achieved in water. But although solvent (e.g., DMSO) stabilization of protonated nitrogen is energetically more eficient[I21, it does not reduce the acidity in a corresponding proportion as long as the possibly more important[I3] solvation of the dissociated protons can operate; this accounts for the weaker solvent response of the nitrogen basicity.The extent of iminium cation solvation may be impeded by spatial restraints to the molecular approach of a given solvent (S). 2,6-Di-tert-butylpyridinium (1) is a well-studied example with the expected acidity in the gas p h a~e [ '~~'~] . Compared with sterically congested aliphatic ammonium ions ['6], the pK, value of 1 is much less diminished from 5.0 in ~a t e r [ '~, '~] to 3.6 in 50% aqueous The proposed explanation[l41 suggests that bonding of a single water molecule (S) at the cationic site might suffice to obtain the usual solvation energy at the expense of ca. 6 entropy units. 3With such background information, we report on the acidity constants and their solvent dependencies for iminium ions 2 and 3, expecting that bulky substituents X and Y andlor R should cause only moderate changes with respect to the sterically less congested analogs from the literature. Steric shielding in our model substances minimizes the possibility of interfering imine hydrolysis and appea...

Prototype Pictet−Spengler Reactions Catalyzed by Superacids. Involvement of Dicationic Superelectrophiles

“…The rate of cyclization is accelerated when the acidity of the medium is increased by the addition of TFSA, as judged from the yield of the cyclized product ( 2a or the benzoyl form of 2a after benzoylation) under unified reaction conditions (50 °C and 1 h): in TFA ( H 0 ≈ −2.7), the cyclized product ( 2a ) is virtually undetectable after 1 h; in the acid of H 0 ≈ −9.0 (1.2% w/w TFSA−98.8% w/w TFA), the cyclized product was formed but in a small amount; in 90% w/w TFSA−10% w/w TFA ( H 0 ≈ −12.5), the yield of 2a was 76%. The p K BH + values of imines 1a − 1 e for N -protonation are estimated to be +6 to +8 . Thus, 1a should be completely protonated to form the monocation 3a even in TFA, where the acidity ( H 0 ) was −2.7 (Scheme ).…”

Conformation versus Coordination: Synthesis and Structural Investigations of Tellurium(II) Dithiolates Derived from β-Donor-Substituted Thiols

“…This result, as well as the increased instability of 4 compared to 1 − 3 , indicates a vital role of the N atom in view of the decomposition reaction. The higher the basicity of the N atom is, the more unstable is the tellurium(II) dithiolate, as can be anticipated by comparison of the p K b values of aniline, 9.38, and ethylamine, 3.0, as a rough measure for the basicities of 2-aminophenylthiol and 2-aminoethylthiol, respectively.

1 Structural formulas of compounds 1 − 4 .

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ChemInform Abstract: Preparation and Characterization of New C2‐ and C1‐Symmetric Nitrogen, Oxygen, Phosphorous, and Sulfur Derivatives and Analogues of TADDOL. Part 3. Some New Chiral Broensted Acids for Organocatalysis and pKa Values in MeO—(CH2)2—OH/H2O — A Survey

“…The pK a values in DMSO (the Bordwell scale) are taken from [46], the pK a values in H 2 O are taken from Marchs textbook [47], and from monographs on amides [48], on sulfonic acid derivatives [49], and on fluoro-compounds [50]. The values for protonated imines R 2 C¼NHR þ and for the phosphoric acid diester ( PhO) 2 P(O)OH are taken from [51] and [52], respectively. OH-groups into close proximity.…”