The intramolecular hydrogen bond and intrinsic proton affinity of neutral organic molecules: N,N ′,N ″‐tris (3‐aminopropyl)guanidine and some related systems

Abstract

AbstractMultiple aminopropyl substitutions of the initial N,N′,N″‐trimethylguanidine lead to high intrinsic absolute proton affinities (APA) and basicities culminating in APA = 268.4 kcal mol−1 (1 kcal = 4.184 kJ) in N,N′,N″‐tris(3‐aminopropyl)guanidine (9). The reason behind a high proton affinity is identified as a strong cationic resonance in the central guanidine moiety and the strength of the intramolecular hydrogen bonding (IMHB), which is enhanced upon protonation. A cooperative IMHB effect in 9 and 9H + realized by three N(sp3)H···N(sp3) H‐bridges is estimated to be as high as 14.7 and 33.0 kcal mol−1, respectively. It follows that the IMHB effect contributes 18.3 kcal mol−1 to the absolute proton affinity of 9, which is a respectable amount. The basicity of 9 in acetonitrile is estimated to be very high, as evidenced by the corresponding pKa = 28.8. A derivative of 9, N,N′,N″‐tris(3‐dimethylaminopropyl)guani‐dine (10), assumes an even higher superbasic proton affinity of 275 kcal mol−1 due to an additional relaxation effect caused by the methyl groups. The corresponding pKa(MeCN) = 29.4. Copyright © 2002 John Wiley & Sons, Ltd.