Successive deprotonation

The parent acids of common polyprotic acids other than sulfuric are weak and the acidity constants of successive deprotonation steps are normally widely different. As a result, except for sulfuric acid, we can treat a polyprotic acid or the salt of any anion derived from it as the only significant species in solution. This approximation leads to a major simplification to calculate the pH of a polyprotic acid, we just use Kal and take only the first deprotonation into account that is, we treat the acid as a monoprotic weak acid (see Toolbox 10.1). Subsequent deprotonations do take place, but provided Kal is less than about fCal/1000, they do not affect the pH significantly and can be ignored. 

Citric acid, which is extracted from citrus fruits and pineapples, undergoes three successive deprotonations with pK, values of 3.14, 5.95, and 6.39. Estimate the pH of (a) a 0.15 m aqueous solution of the monosodium salt (b) a 0.075 M aqueous solution of the disodium salt. 

Although deprotonation at the benzylic position of arenes coordinated to ruthenium and chromium was reported,27 in the case of the coordinated oxo-ri5-dienyl unit, nucleophilic attack at one terminus of the complexed r 5-dienyl ligand, rather than deprotonation, was expected.28 The reason for the successful deprotonation (even at relatively hindered isopropyl sites) is, according to the authors, the cationic nature of the Cp M fragment. In addition, the transition state for the deprotonation might involve stabilization by the metal (Scheme 3.15). 

The second method is the more general one. The choice of the base depends on the acidity of the hydrido complexes. In most cases KH, NaH or LinBu are very suitable. For the more acidic complexes, amines are also convenient. Complexes of low acidity were successfully deprotonated by KH/18-crown-6. 

A strong decrease in relaxivity (from 12.8mM-1s-1 to 2mM-1s-1) between pH 6 and 11 has been reported for a positively charged macrocyclic Gdm complex (Scheme 10), which was explained by the successive deprotonation of the coordinated water molecules.167 Luminescence lifetime measurements of a Yb111 analogue proved that the complex possesses three bound waters at pH 5.5. Above pH 11, a di-oxo-bridged dimer is formed that has no more bound water or OH groups. 

Imines derived from macrocyclic ketones (C10 to C 15 ) and (- )-(S)-a-(methoxymcthyl)benzene-ethanamine are successfully deprotonated using LDA ( —25 JC. THF. 1 h)9. In contrast to azaenolates of C0- to C8-membered cyclic ketones, which show only E geometry, Z-isomers are observed with macrocyclic imines. As evident from H-NMR data, azaenolates of cyclodecanone imines generated under these conditions are a mixture of E- and Z-isomers (33 66), whereas azaenolates of cyclododecanone and cyclopenladecanone imines arc formed as the pure. E-isomers (see Table 3). Upon heating the solutions of metalated imines to reflux for 1 hour, complete isomerization to the thermodynamically more stable Z-isomers occurs. 

The deprotonation-silylation of /V-alkylated benzotriazoles has been tested. Successive deprotonation-silylation of benzotriazoles leads to iV-trimethylsilylmethyl-and Al-bis(trimethylsilyl)methylbenzotriazole.156 157... 

A sequence involving formation of two organolithiums by successive deprotonation and reduction steps allows the introduction of an electrophile either axially or equatorially at the anomeric position of a glycoside.89 Direct reductive lithiation of 98 gives axial 99 and hence... 

The alkylation of different polymeric reagents 268 (prepared from the corresponding odorless 1,3-dithiols and aldehydes) has been performed by successive deprotonation with n-BuLi and reaction with alkyl bromides and iodides. Final oxidation with periodic acid or with mercury(II) perchlorate gave the corresponding ketones (Scheme 73)452. 

The dark blue crystalline l,3-bis(dimethylamino)pentalene (157) was the second derivative to yield to synthesis (Scheme 26).233-1 Upon condensation of sodium cyclopentadienide with the salt 153, there is obtained the fulvene 154 which can be cyclized with loss of dimethylamine when heated in xylene. Treatment of the resulting ketone (155) with dimethylammonium perchlorate afforded the salt 156 which was successfully deprotonated with isopropylmagnesium bromide. Interestingly, 155 could be reversibly converted to its blue-colored enolate without polymerization or decomposition. 

We also observed similar phenomena in the reaction of silyl enol ethers with cation radicals derived from allylic sulfides. For example, oxidation of allyl phenyl sulfide (3) with ammonium hexanitratocerate (CAN) in the presence of silyl enol ether 4 gave a-phenylthio-Y,5-un-saturated ketone 5. In this reaction, silyl enol ether 4 reacts with cation radical of allyl phenyl sulfide CR3 to give sulfonium intermediate C3, and successive deprotonation and [2,3]-Wittig rearrangement affords a-phenylthio-Y,6-unsaturated ketone 5 (Scheme 2). Direct carbon-carbon bond formation is so difficult that nucleophiles attack the heteroatom of the cation radicals. 

In solutions with pH < 5, aluminum occurs as the octahedral hexahydrate, A1(H20)6 ", usually abbreviated as AP+. As a solution becomes less acidic, A1(H20)6 " undergoes successive deprotonations to yield Al(OH) +, A1(0H)2+, and soluble Al(OH)3, with a decreasing and variable number of water molecules. Neutral solutions give an Al(OH)3 precipitate that redissolves, owing to formation of tetrahedral aluminate, Al(OH)4, the primary soluble AP+ species at pH > 6.2. The four successive deprotonations squeeze into a narrow range 5.5 < pH < 6.2 the deprotonations from octahedral hexahydrate to tetrahedral aluminate occur cooperatively. ... 

In the metalation reaction of pyridine 5 with tBuLi the methoxy substituent exhibits a directing effect. Solvated (tBuLi)4 aggregate 19 coordinates to the oxygen of the methoxy group to give 20. Successive deprotonation yields the ortljo-lithiated species 21, which is stabilized by 0-Li coordination. 

Successful deprotonations must discourage equation (11) so as to allow equation (10) to proceed. This may be achieved in several ways as follows (a) the reagent can be a very hindered, non-nucleophilic base (b) the groups around boron can be large so that attack on boron is inhibited on steric grounds or (c) the electrophilicity of the boron atom may be lowered by the use of heteroatom substituents (e.g. equation 10 X = OR). All three of these approaches have been used, either separately or in conjunction with one another. 

Even using LITMP it was not possible to convert (13) into (14) when X = H (equation 13). It appears that stabilization by one dialkoxyboryl group is not sufficient and that at least one other stabilizing group is required for anion formation. Deprotonation with LITMP was successful for (13) with X = Ph, SPh,3i TMS,32.33 PhjP 33 and CH=CH2,33 but failed for X = MeaS 33 and R3N+.3 Compound (15 X = H equation 14) is successfully deprotonated by LITMP in the presence of TMEDA to give (16 X = H). Unfortunately, with (15 X = Ph), cleavage takes precedence over deprotonation and (14 X = Ph) is produced rather than (16 X = Ph).3°... 

The commonly used bases in this reaction are commercially available solutions of n-BuLi (in hexane) (140-146), or n-Bu2Mg (in heptane) (144) freshly prepared lithium amide LiNH2 has also been used for the synthesis of lithium methylthiolate (147). Similarly, several bulky arenethiols (e.g., HSC6H2Ph3-2,4,6) have been successfully deprotonated with either a 1 1 mixture of n-Bu,Mg and s< c-Bu2Mg in heptane or Mg N(SiMe3)2 2 in toluene (148). A major shortcoming of this procedure is that thiols that are not commercially available have to be prepared via metal thiolate species—clearly a roundabout approach. 

The pH of a Polyprotic Acid Solution Successive deprotonations of a polyprotic acid... 

Successive deprotonation of [P NH(Ph) ]+ was followed by 31P NMR spectroscopy.1110 Formation constants for adducts of C60 and C70 with a number of phosphine oxides were calculated from 3H chemical shift changes in the systems.1111 Variable temperature 1H NMR spectra of [L]BiN03, where L =... 

The a-chlorophosphonates are valuable intermediates that have applications in the synthesis of alkynes, chloroolefins, and 1,2-epoxyphosphonates. Tetrachloromethane seems to be the most widely used reagent in the electrophilic monochlorination of phosphonates, presumably because it gives very clean chlorine transfer and produces an easily removed byproduct (chloroform) (Scheme 3.27). Only leq of base (n-BuLi) is needed to achieve the two successive deprotonations. A large number of chloroalkenes, some of them showing interesting insecticidal properties, have been obtained in 27-87% yields by this method (Scheme 3.27). ... 

Deprotonation of water enhances the prospect of bridging between two metal ions by increasing electron density on the O atom. Successive deprotonation can permit multiple bridging to metal ions, resulting in small metal-oxide clusters. 

For the corresponding Pt(II) complex, enPt(OH2)2 " > endpoint is reached after addition of two equivs base. The dimerization proceeds slowly, and it is possible to resolve the titration curve obtained at 23° with 0.2 M KNO3 into two successive deprotonations (11) with pK] 5.8 for formation of the aquo-hydroxo complex and pK2 = 7.6 for formation of the dihydroxo complex. If only one equiv base is added to enPt(OH2)2 the solution containing predominantly the aquo-hydroxo complex is allowed to stand, no titrable groups remain (11). Thus dimerization does occur, but more slowly than with the corresponding Pd(II) complex. 

---