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

Multiple 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(sp 3 )H···N(sp 3 ) 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 p K a = 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 p K a (MeCN) = 29.4.