Proton Affinities of Phosphines

Differences in the availability of the P lone pair for a series of phosphines are likely to have profound effects on their biological chemistry. For instance, the question arises as to whether a particular phosphine is likely to become protonated in vivo. The pKa s of hydrophobic phosphines can not be measured in H2O. Consequently most of the experimental data have been obtained by titration in non-aqueous media (usually nitro-methane). Conversion to aqueous pKj values is usually carried out using a relationship between half neutralisation potentials in CH3NO2 and pKa(H20) that exists for amines. For monodentate tertiary phosphines, introduction of phenyl-substituents lowers the pKa (Table 2). There appear to have been no similar determinations of the pKa s of diphosphines. It seems likely that phenyldiphosphines (e.g. dppe) are weakly basic (pKa 3) and therefore will not be significantly protonated at pH 7. Preliminary experimental data measured by R. Norman in our laboratory suggest that this is the case .  

However, solvation effects can have a major influence on the pKj. In the gas phase PPh3 is apparently a stronger base than the opposite of that found from pK, 

In a biological system solvation effects will clearly be important. It is difficult to predict whether pKj s or gas-phase proton-affinities will be more reliable guides to the degree of protonation of phosphines in vivo. There are a variety of compartments of greatly differing polarities that are potentially available. Lipophilic phosphines would be expected to become localised in non-aqueous environments, e.g. membranes. It is possible that a phenyldiphosphine could act as a H shuttle across a membrane. The only way to probe this may be to investigate whether proton translocation occurs in a model system. 

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Waddington reported an approximately similar value of 194.5 5 kcal/mol. Both these results agree well with that reported by Holtz and Beauchamp for the proton affinity of phosphine. These workers determined the proton affinity from ion molecule reactions of the type... 

The reactions 2 and 3 in Table 5 set the limits for the proton affinity of phosphine. Reaction 2 shows that it is smaller than that of acetone (186 3 kcal/mol) and reaction 3 indicates that it is larger than the proton affinity of acetaldehyde (185 3 kcal/mol). Thus a value of 185 ... 

Also the value reported by Haney and Franklin of 186 1 kcal/mol is in agreement. The latter workers determined the proton affinity of ammonia as 207 kcal/mol which is approximately 21 kcal/mol larger than that for phosphine. The greater basicity of ammonia as compared to phosphine is showi by the difference of about 20 pH units in their relative basicities in aqueous solutions. The difference in the basicities of the aqueous solutions of 23-32 kcal/mol, which is comparable to that in the gas phase, leads to the somewhat surprising conclusion that solvent effects appear to play an unessential part in the relative basicities of PH3 and NH3 in aqueous solutions. The proton affinities of HjO and H2S, 164 and 170 kcal/mol, respectively, are in the reverse order. 

Gas phase proton affinities of phosphabenzene and arsabenzene have been determined by ion-cyclotron resonance techniques 94>. These confirm the qualitative solution phase data (see Fig. 5). Phosphabenzene (PA = 194.5 kcal/mol) has a proton affinity nearly 30 kcal/mol less than trimethylphosphine and only slightly greater than that of phosphine. Arsabenzene (PA = 188.0 kcal/mol) has a proton affinity 23 kcal/mol less than trimethylarsine. In the case of arsabenzene, protonation occurred on carbon rather than arsenic so the As-basidty may be even lower. By contrast, the proton affinity of pyridine (PA = 218 kcal/mol) is only slightly less than that of trimethylamine (PA = 222 kcal/mol) but considerably larger than ammonia (PA = 202 kcal/mol). 

Fig, 5. Gas phase proton affinities of pyridine, phosphabenzene and arsabenzene compared to selected amines, phosphines and arsines... 

The structures of fluorophosphine, PH2F, and chlorophosphine, PH2CI, have been determined by ab initio calculations, and the pyramidal geometry of the X Ai ground state of the Pp3 cation has been confirmed. An ab initio study of the internal rotation levels of the terminal methyl group in the ethylphosphine molecule CH3CH2PH2 has been undertaken. Ab initio calculations on ethyldi-fluoro-, ethyldichloro-, and ethyldimethyl-phosphines, CH3CH2PX2 " have been compared with conformational stabilities obtained from temperature-dependent FT-IR spectra recorded in liquefied xenon solutions. Theoretical gas-phase proton affinities of arylphosphines have also been reported at the MP2 level. 

Glidewell and Thompson26 calculated the gas-phase proton affinity of H3SiNH2 to be about 9 kcal mol1 smaller than that of H3CNH2. Data for some calculated proton affinities of silylamines and phosphines are given in Table 9. Substitution of successive methyl groups into ammonia caused an increase in proton affinity, as predicted by simple... 

Kovacevic, B. and Maksic, Z.B. (2006) High basicity of phosphorus-proton affinity of tris-(tetramethylguanidylphosphine) and tris(hexamethyltriaminophosphazenyl)phosphine by DFT calculations. Chemical Communications, 1524-1526. 

The stability of the complexes again appears to be related to the proton affinity of these molecules and is illustrated in Table III and Fig. 9. Values for the mcp are given for 3 1, 2 1 and 1 1 complexes in the table. Since only some of the phosphines form 3 1 complexes it is impossible to make correlation. The 1 1 complexes obviously do not correlate with pKa(H ) as in the case of the amines. A plot of mcp for the 2 1 complexes vs. pKa is given in Fig. 9. The data are minimal but it appears... 

As can be seen, the diphenylguanidine and presumably all of the alkyl amines are strong enough bases to protons to form the N-H bond in preference to the N-Ag. Summation of meq for each quantity gives the total for meq taken. The greater stability of the P-Ag bond and lower proton affinity of the phosphine phosphorus for hydrogen gives a more complex picture for the phosphines. The... 

Indeed, pKa measurements indicate that the donor ability of PR3 towards protons in solution decreases with increasing substitution of phenyl groups (Table 2). However, Puddephatt and coworkers have suggested that this order should actually be reversed on the basis of the relative lone pair ionisation potentials and proton-affinities of these phosphines in the gas phase (see Table 2). The role of solvent in determining pKa s is discussed in Sect. 4.6. 

The measure of basicity of phosphine hgands most widely quoted in the hterature is p/fa (aqueous), which is a measure of Bronsted basicity or proton affinity. A selection of pA a values for various phosphines is given in Table 4. AngeUci and coworkers have established a method for determining proton affinities from enthalpies of protonation using the extremely powerful acid CF3SO3H. The enthalpy values (A//hp) and pATa values are related by the empirical equation (3) ... 

Some recent quantum mechanical calculations show that all P-donor ligands, PX3, are good <7 donors, including PF3. These calculations estimate that the a donor contribution to the proton affinity is only 10% larger in PMes than in PF3. Thus, the controversy about the significance of phosphine basicities is far from settled. 

Mechanistic Studies. - The mechanism of the reaction of tetra-zole-activated phosphoramidites with alcohols has been studied. A series of diethyl azolyl phosphoramidites (85) was prepared from diethyl phosphorochloridite and fully characterized, and the same compounds shown to be formed from the phosphoramidite (86) and azole. The degree of formation of (85) from (86) increases with the acidity of the azole, and the proposed mechanism is a fast protonation of (86), followed by a slow, reversible formation of (85) and a fast reaction of (85) with alcohols. Another study was concerned with the influence of amine hydrochlorides on the rate of methanolysis of the phosphoramidites (87) or (88), or tris(diethylamino)phosphine.The chloride content was measured to be 10-20 mM in doubly distilled samples which explains that "uncatalysed alcoholysis is possible. Intensive purification, including treatment with butyllithium and distillation from sodium, brought the chloride content down to 0.1-1 mM. The methanolysis reaction, in methanol as the solvent, was found to be first-order in catalyst concentration. An aJb initio calculation on N- and P-protonated aminophosphine (89) gave similar proton affinities for N and P this contrasts with earlier MNDO calculations which had ff-protonated species as the most stable. The M-protonated compound had an electronic structure reminiscent of a phosphenium ion-ammonia complex. 

An analysis of the effects of substituents on the basicity of phosphines has been presented,and the relationship between phosphine-proton affinities and lone pair density properties explored. A scale of a-donor strengths for phosphines and related systems has been developed. The model supports the view that as a-donor strength increases, so the 7C-acceptor power declines. Theoretical approaches to the electronic structures of phosphirane and 1,3-diphosphe-... 

The ordering of the electronic transitions in the (phosphine)2Pt S2C2(Het) (R ) complexes depends on the appended heterocycle. For these complexes the energy of the ILCT transition tracks with the reduction potential and hence the electron affinity of the heterocycle [30]. Consistent with this observation, the energy of the transition is lowei by protonation and alkylation of the heterocycle (see Section VI) [30-35]. 

In summary, it appears that the formation of silver complexes is a function of proton affinity and ultimately of 2a values for both phosphorus and nitrogen compounds. However, the stability of the complex depends on the extent of the substitution. The utility of silver ion for titration of compounds of the phosphine class is potentially much more useful than for the amines. It is probable that silver titrations can be used to differentiate P and N atoms either in mixtures or in a single molecule. 

The role of hybridization and basicity in the gas phase has been discussed further by Aue [25], who draws attention to the low basicity of aziridine as against dimethylamine when compared with the other pairs of cyclic and acyclic compounds, and points out that acetonitrile is about 34kcalmol lower in proton affinity than is ethylamine. Beauchamp [26] has considered the importance of hybridization in comparing the effects of alkyl substitution on phosphines compared to amines. 

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