Proton loss

In an aquo-complex, loss of protons from the coordinated water molecules can occur, as with hydrated non-transition metal ions (p. 45). To prevent proton loss by aquo complexes, therefore, acid must usually be added. It is for these conditions that redox potentials in Chapter 4 are usually quoted. Thus, in acid solutions, we have... 

Compound Proton gain Proton loss first second ... 

Proton loss from a ring nitrogen atom... 

The mode of attack of electrophilic reagents (E ) at ring carbon atoms is jS to the heteroatoms as shown, for example, in (11) and (12) the intermediates usually revert to type by proton loss. Halogenation takes place more readily than it does in benzene (Section 4.02.1.4.5). Nitration and sulfonation also occur however, in the strongly acidic environment required the compounds are present mainly as less reactive hydroxyazolium ions, e.g. (13). 

In azoles containing at least two annular nitrogen atoms, one of which is an NH group and the other a multiply-bonded nitrogen atom, electrophilic attack occurs at the latter nitrogen. Such an attack is frequently followed by proton loss from the NH group, e.g. (66) (67). If the electrophilic reagent is a proton, this reaction sequence simply means... 

In addition to reaction sequences of type (66) -> (67), electrophilic reagents can attack at either one of the ring nitrogen atoms in the mesomeric anions formed by proton loss e.g. 70 71 or 72 see Section 4.02.1.3.6). Here we have an ambident anion, and for unsymmetrical cases the composition of the reaction product (71) + (72) is dictated by steric and electronic factors. 

Table 2 pK Values of Azoles for Proton Loss [Pg.50]

Neutral azoles are readily C-lithiated by K-butyllithium provided they do not contain a free NH group (Table 6). Derivatives with two heteroatoms in the 1,3-orientation undergo lithiation preferentially at the 2-position other compounds are lithiated at the 5-position. Attempted metallation of isoxazoles usually causes ring opening via proton loss at the 3-or 5-position (Section 4.02.2.1.7.5) however, if both of these positions are substituted, normal lithiation occurs at the 4-position (Scheme 21). 

Substituted imidazoles can be acylated at the 2-position by acid chlorides in the presence of triethylamine. This reaction proceeds by proton loss on the (V-acylated intermediate (241). An analogous reaction with phenyl isocyanate gives (242), probably via a similar mechanism. Benzimidazoles react similarly, but pyrazoles do not (80AHC(27)24l) cf. Section 4.02.1.4.6). 

Proton loss Hydroxyl Are acidic Carboxylic acid... 

Reactions of types (i)-(vi) can be catalyzed by alkoxide or hydroxide ions, or amines. Alternatively, an acid catalyst forms a complex of type (380) from which proton loss is facilitated. 

Proton loss from alkyl groups a or 7 to a cationic center in an azolium ring is often easy. The resulting neutral anhydro bases or methides (cf. 381) can sometimes be isolated they react readily with electrophilic reagents to give products which can often lose another proton to give new resonance-stabilized anhydro bases. Thus the trithione methides are anhydro bases derived from 3-alkyl-l,2-dithiolylium salts (382 383) (66AHC(7)39). These... 

Canonical forms of type (442b) facilitate proton loss from the amino groups the anions formed react easily with electrophilic reagents, usually preferentially at the exocyclic nitrogen atom e.g. 443 -> 444) (79HC(34-2)9). 

Azolinones are protonated on oxygen in strongly acidic media. O-Alkylation of 2-azolinones can be effected with diazomethane thiazolinone (486) forms (487). Frequently O- and iV-alkylation occur together, especially in basic media where proton loss gives an ambident anion. 

Both proton loss and rearrangement reflect the greater positive charge at carbon in a chloronium ion than in a bromonium ion because of the weaker bridging by chlorine. 

All the rearranged products derived from (12) and (15) have been rationalized as arising by proton loss or reaction with fluoride ion of the respective homoallylic C-19 cations. The structures of the cations derived from (15) are represented by structures (20) to (24)." ... 

The mechanism is presumed to involve a pathway related to those proposed for other base-catalyzed reactions of isocyanoacetates with Michael acceptors. Thus base-induced formation of enolate 9 is followed by Michael addition to the nitroalkene and cyclization of nitronate 10 to furnish 11 after protonation. Loss of nitrous acid and aromatization affords pyrrole ester 12. 

Keto-enol tautomerism of carbon) ] compounds is catalyzed by both acids and bases. Acid catalysis occurs by protonation of the carbonyl oxygen atom to give an intermediate cation that Joses H+ from its a carbon to yield a neutral enol (Figure 22.1). This proton loss from the cation intermediate is similar to what occurs during an El reaction when a carbocation loses H+ to form an alkene (Section 11.10). 

The values of kH/kD for the uncatalysed and catalysed reactions were 4.36 and 4.47 respectively, yet the isotope effect is not necessarily diminished on reducing the concentration of iodide ion to zero and by the arguments elaborated above (p. 95) this implies that molecular iodine is not the iodinating species and that this species is formed in some pre-equilibrium, the function of the base being to form the species and not to remove the proton. This argument assumes, as does the previous discussion of the effect of iodide ion concentration on isotope effects, that a minute concentration of I- is insufficient to compete effectively with the reaction involving proton loss. 

There is one further piece of kinetic evidence which throws light on an aspect of the benzidine rearrangement mechanism, and this is comparison of the rates of reaction of ring-deuterated substrates with the normal H compounds. If the final proton-loss from the benzene rings is in any way rate-determining then substitution of D for H would result in a primary isotope effect with kD < kH. This aspect has been examined in detail42 for two substrates, hydrazobenzene itself where second-order acid dependence is found and l,l -hydrazonaphthalene where the acid dependence is first-order. The results are given in Tables 2 and 3. 

The conclusion from the experiments with ring-deuterated substrates is that the final proton-loss from the aromatic rings is not rate determining although in some cases it may effect the product distribution. 

Proton electrochemical gradient. 6,714 Proton exchange amine ligands, 2, 24 Proton loss catalysis... 

The formation of 33 in the case of 32 can be explained by attack of some of the CCI2 ipso to the CH3 group. Since this position does not contain a hydrogen, normal proton loss cannot take place and the reaction ends when the CCli" moiety acquires a proton. 

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