Amidines hydrogen bonding

The structural investigations have been extended to potassium derivatives of the "super" formamidine HC(NC6H3Pr2-2,6)(NHC6H3Pr2-2,6) ( = HDippForm). Treatment of the free formamidine with KN(SiMe3)2 yielded the formamidinate species [K(DippForm)2K(THF)2l (THF) , which exhibits a macromolecular structure of alternating fj -arene f/ -amidinate bound potassium di-amidinate and potassium di-THF units in a one-dimensional polymeric array (Figure 5). Addition of a further equivalent of HDippForm afforded hydrogen-bonded [K(DippForm)(THF)3](HDippForm). ... 

Oxidative attack on a carbon-hydrogen bond of an alkyl group a to a nitrogen atom is not restricted to saturated aliphatic amines. In fact X in an X-N-CH- structural subunit can be virtually any common atomic grouping that can be found in stable organic molecules. For example, w-carbon hydrogens of Aralkyl-substituted aromatic cyclic amines (119), aryl amines (120), amides (121), amidines (122), A-nitrosodialkylamines (123), etc. are all subject to oxidative attack, carbinolamine formation, and in most cases release of an aldehyde or ketone depending on the substitution pattern (1° or 2°)... 

Optically active phosphine monoester 69 was prepared as a stable transition state analogue of the hydrolysis of 70, and used as a template (Scheme 13.17) [52], When heated in the presence of amidine 72, methyl methacrylate, ethylene glycol dimethacrylate and AIBN, polymerization took place and offered the polymer 73, in which the template 69 is attached to the binding sites by a combination of hydrogen bonds and electrostatic interactions. After washing in the presence of MeOH and aqueous NaOH, the template was removed from the cavity, thus leading to a catalytically active MIP. 

These reactions usually are slow at room temperature, and the adhesives must be cured with heat. Tertiary amines or amidines can be used to catalyze the reaction whereby the car-boxylate anion is the nucleophile and the ammonium or amidinium ion act as hydrogen-bond donors. Dusek et al. have shown that transesterification only occurs after essentially complete consumption of the carboxylic acid in compositions initially having equivalent amounts of acid and epoxy groups.40 41 The transesterification leads to an equilibrium sol-gel composition. 

The considered functional groups are those having some hydrogen-bonding capabilities that are essential for specific drug interactions with the target. These are called pharmacophore points and include amine, amide, alcohol, ketone, sulfone, sulfonamide, carboxylic add, carbamate, guanidine, amidine, urea, and ester. 

Given the earlier enunciated anomalies of McjN and CHO substitution, again the two sets of results are not particularly discordant. Indeed, from the data in Table 1, we derive the difference of enthalpies of formation for R = PhNH and = CH=NPh with = 1 and 2[<5A/f,(s, 18a, 18b)] to be 64 kJ moP Given the additional complication of intra- and intermolecular hydrogen bonding occurring in these vinylogous amidines, it would seem that all of these results are plausible. ... 

Free rotation about the C—N bond in acyclic amidines can place the hydrogen attached to the N(sp3) in a very accessible position to the lone pair of the N(sp2), producing intramolecular hydrogen bonding that enables proton migration. 

In contrast, in cyclic amidines free rotation does not occur, and conformational changes of the ring system cannot lead to intramolecular hydrogen bonding. Only intermolecular proton transfer is possible. Confirming this interpretation is the observation that in cyclic amidines a concentration dependence is observed on the rates of tautomerism, whereas in acyclic systems the proton transfer is independent of concentration. 

In Fig. 6.38(a) are depicted the correlated NHN-hydrogen bond coordinates (Table 6.5) of porphyrin, of TTAA, porphycene, of the pyrazoles discussed in the previous section, as well as the calculated values of the transition states of porphyrin [65] and of its mono-deprotonated anion [81]. Also the data point of the double proton transfer in the cyclic N,N -di-(p-F-phenyl)amidine dimer was added, which is discussed in the next section as it involves a hydrogen bond pre-equilibrium and a coupling to the reorientation ofthe aryl groups. 

Figure 6.43 Conformational isomerism, hydrogen bond exchange and HH-transfer in N,N -di-(p-F-phenyl)amidine (DFFA) dissolved in tetrahydrofuran (S) according to Ref [24cj.

That such a delicate balance exists between tautomers is not an obvious prediction based solely on ApK s. The 10 pK unit difference in 9 benzoate favors the amidine-carboxylic acid form by 0.6 eV. However, a simple electrostatic calculation [123] for a positive and negative charge at a salt bridge distance of 3.8 A translates into a stabilization energy of-0.50 eV in the solvent THF, which nearly offsets the stabilization of the amidine-carboxylic acid tautomer derived from the ApfQ. Electron-rich carboxylates such as benzoate are sufficiently basic that the amidine-carboxylic acid hydrogen bond interaction prevails while the interface retains its ionic nature for more acidic carboxylic acids and various sulfonic acids. 

Some racemic compounds might be separated without the need to make chemical derivatives. Chiral diols bond selectively (55-isomer favored over the i i -isomer by a factor of 6 or 7) by hydrogen bonding to the amidine (10.28).56... 

Fe(77 -C5H4COOH)2] has been widely employed as a building block in supramolecular chemistry, because the carboxylic groups can easily react and form hydrogen bonds with bis-amidines or diamines. For example, an acid base stoichiometric ratio of 2 1 allows partial deprotonation of the acid, thus affording species that show the... 

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