Mono-protonation

Aminopyridines, aminopyridine oxides, and 3-aminoquinoline are obviously diazotized by analogous mechanisms. Kalatzis (1967 b) studied the diazotization of 4-aminopyridine over a very large range of acid concentrations (0.0025-5.0 m HC104). This compound is comparable to 2-aminothiazole in its acid-base properties the heterocyclic nitrogen is easily protonated at pH 10, whereas the amino group is a very weak base (pKa = -6.5). Therefore, the kinetics indicate that the (mono-protonated) 4-aminopyridinium ion reacts with the nitrosyl ion. The... 

The Polar-Transition-State theory based on earlier ideas by Hughes and Ingold49, has as its main feature the heterolysis of the N-N bond in the mono- or di-protonated hydrazo molecule as the transition state is approached, with a de-localisation of the positive charge in the mono-protonated case and of one of the positive charges in the di-protonated case, viz. (16) and (17), respectively... 

Two other theories as to the mechanism of the benzidine rearrangement have been advocated at various times. The first is the rc-complex mechanism first put forward and subsequently argued by Dewar (see ref. 1 pp 333-343). The theory is based on the heterolysis of the mono-protonated hydrazo compound to form a n-complex, i.e. the formation of a delocalised covalent it bond between the two rings which are held parallel to each other. The rings are free to rotate and product formation is thought of as occurring by formation of a localised a-bond between appropriate centres. Originally the mechanism was proposed for the one-proton catalysis but was later modified as in (18) to include two-protons, viz. 

The reaction of the in situ generated reagent Li2[PhP(N Pr)3] with [(q-p-cymene)RuCl2]2 yielded, after work-up, [(q-p-cymene)Ru q -( PrN)2PPh-(NH Pr) ] [BPh4] (26). Apparently, mono-protonation of the initial reaction product occurred during the isolation procedure. 

The term p[H] represents the pH value of the solution expressed on a concentration scale [5], where [H] represents the concentration of hydrogen ions H+. P° represents the partition coefficient of the unprotonated species, P1 is the mono-protonated species, and so on. P may also be expressed as... 

Condensation of the carbonyl function with an amine from a second 1,2-diaminoethane molecule coupled with a repeat of the initial reaction sequence will lead to the cyclic product. It is of interest that this is one case in which the synthesis will also proceed in the absence of a metal ion. Starting from a mono-protonated salt of 1,2-diaminoethane in acetone, the metal-free condensation may proceed via a reaction such as [2.7], Once again, a hydrogen-bonding network may act as a template for the reaction and also serve to stabilize the product once it is formed. A revised synthesis of the metal-free ligand (61) has been published (Hay,... 

It was proposed that mono-protonation of [CuL]2+ to yield [Cu(HL)]2+ occurs initially at the axial nitrogen atom since this Cu-N bond is expected to be weaker as a result of Jahn-Teller distortion. With respect to this, it should be noted that species such as [Cu(HL)]3+ are commonly observed during potentiometric studies of the formation of Cu(n) polyamine complexes. From the proposed mechanism, the following rate law can be deduced ... 

Protonolysis with weak acids such as ethanol gives mono-protonated dienylzirconocene compounds 15a (Eq. 2.11), which can be converted into substituted diene derivatives 16 [21]. 

The crystal structure of just one carbamoylguanidine co-ordination complex, [Cu(clge)2][N03]2 has been reported [55],although the structure of [clgeH]2 [Cu(OH2)2C14], containing the mono-protonated carbamoylguanidine cation, has also been described [56]. 

While all strain effects in monoamines are basicity weakening, it is possible to find cases in di- and polyamines where strain is relieved upon protonation, leading to increased basicity. This phenomenon is observed in 1,4-diaminobutane derivatives where an almost linear N... H—(N+) hydrogen bond in the mono-protonated derivatives leads to a stable, seven-membered ring structure. Thus, for example, the measured PA of l,6-diazabicyclo[4.4.4]tetradecane (73) is 228.3 kcalmol-1, about 11 kcalmol-1 higher than its monoamine analog 75, despite the similar, inwardly pyramidalized, nitrogen conformation of both neutral amines. 

The reaction of hydrazobenzene (1) refers to reaction via the doubly protonated form. The mechanism for the rearrangement via a mono protonated form was examined17 using 2,2 -dimethoxyhydrazobenezene (7). Again the KIE results for formation of the benzidine derivative 8 show that reaction is also concerted. It appears that there is no major difference between the one- and two-proton reactions. 

Protonation to the conjugate acid (iminium cation) increases the potential of the itnine to act as an electrophile (compare carbonyl see Section 7.1), and this is followed by nucleophilic attack of water. The protonated product is in equilibrium with the other mono-protonated species in which the nitrogen carries the charge. We shall meet this mechanistic feature from time to time, and it is usually represented in a mechanism simply by putting H+, +H+ over the equilibrium arrows. Do not interpret this as an internal transfer of a proton such transfer would not be possible, and it is necessary to have solvent to supply and remove protons. 

Figure 3.61 X-ray molecular structure of mono-protonated Me3[9]ane-N3 (C104 salt) showing the...

We have carried out calculations on some charged species (compounds 90-93, Figure 20) to check the observation, previously reported, that cations and metal complexes have lower 0 values (4.6°) than neutral TBs. The results show that quaternary ammonium salts have r/j angles about 5° lower than protonated cations (that duplicates in double salts). Mono-protonation alone is not sufficient to modify r/j (compare 89 and 90) actually if one compares the neutral DILLEP (92.9 and 97.4°) with the mono-protonated derivative SIYTOG (97.6°) and the mono-quaternary salt DEGRIQ (86.2°), the quaternary salt has a value 11.4° lower that the protonated cation which is similar to the neutral molecule. 

The total energies of various conformers of dibenzo-l,5-dithiocin oxides 815 and 816 obtained by ab initio MO calculations indicated that the BC forms were the more stable than the TB forms (0.0 and 28.0kJmoP1 for 815, respectively, while —5.2 and 7.6 kj mol-1 for 816, respectively). The calculated interatomic distance between two sulfur atoms in the TB form of 815 was almost the same as that in dibenzodithiocin 817. The ab initio MO calculations were performed also on the mono-protonated and the di-protonated 1,5-dithiocin 815a, 816a and 815b, 816b, respectively. 

As an aside, it is noted that the latter may not be a hard and fast rule, at least when other ligand types are present. Sauvage, Balzani et alP used NMR data as well as absorption and fluorescence results to demonstrate the protonation-driven formation of a double-helical structure involving two ligand strands derived from a pair of 2-/ -anisyl-l,10-phenanthroline units linked in their 9-positions by a 1,3-phenylene spacer. In this case, the first protonation step does not simply represent mono-protonation of one of the phenanthroline units but rather appears to involve a co-operative interaction with a pair phenanthroline units (on different strands). 

Taken together, these two structures, the only ones so far obtained for mono-protonated sapphyrin derivatives, are important. They demonstrate clearly that, at least in the solid state, sapphyrins need not be doubly protonated to bind anions. These results thus provide critical structural support for the notion that sapphyrins could prove useful as anion receptors in solution. This is because in aqueous media it is the mono-, not the diprotonated, form of sapphyrin that dominates at or near neutral pH vide infra) ... 

Figure 5 (a) Structure of HEV-l PR [103] and its cleavage site (b) models used for the ab initio molecular dynamics of the mono-protonated form.(Reproduced with permission from ref. [100], Copyright 2000 Wiley.)... 

Protonation State. At optimal pH for enzymatic activity ( 5-6) [101, 102, 105], the Asp dyad can in principle exist in three protonation states, a deprotonated, a mono-protonated or a doubly protonated form. Because hydrogen atoms cffe invisible in the X-ray structure, evidence for a specific protonation state must be inferred indirectly by spectroscopic or titration measurements. Up to now, the existence of the doubly protonated, neutral form hfree enzyme. The existence of the deprotonated, doubly negative form is supported by a recent NMR study [102] at pH 6. However, this study has been subjected to criticism [106] and it is not conclusive. Our ab initio simulations of this form show that the Asp dyad is unstable even in the ps timesccde because of the strong Asp-Asp repulsion, which turns out to be -t-30 kcal/mol as estimated with a simple electrostatic model [100]). Thus, our calculations do not support the existence of this form. 

The third possible state is the mono-protonated one, which has been strongly suggested from both experiment and theory [101, 106]. 

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