Effects of Electrolytes on the Dediazoniation of Aryldiazonium Ions in Acidic MeOH/H2O Mixtures

Aryldiazonium, ArN 2 , ions decompose spontaneously through the formation of highly reactive aryl cations that undergo preferential solvation by water, showing a low selectivity towards the nucleophiles present in their solvation shell. In this work, we investigate the effects of electrolytes (NaCl, LiCl, and LiClO4) on the dediazoniation of 2-, 3-, and 4-methylbenzenediazonium ions in acidic MeOH/H2O mixtures. In the absence of electrolytes, the rates of dediazoniation, kobs, increase modestly upon increasing the MeOH content of the reaction mixture. At any solvent composition, the rate of ArN 2 loss is the same as that for product formation. The main dediazoniation products are cresols (ArOH) and methyl phenyl ethers (ArOMe). Only small amounts (less than 5%) of the reduction product toluene (ArH), which are detected at high percentages of MeOH. Quantitative yields of are obtained at any solvent composition. The addition of LiCl or NaCl ([MCl] = 0–1.5 M) to the reaction mixtures has a negligible effect on kobs but leads to the formation, in low yields (<10%), of the ArCl derivative. The addition of LiClO4 (0–1.5 M) to 20% MeOH/H2O mixtures has a negligible effect on both kobs and on the product distribution. However, at 99.5% MeOH, the addition of the same amounts of LiClO4 leads to a modest decrease in kobs but to a significant decrease in the yields of ArOMe. Results are interpreted in terms of the preferential solvation of perchlorate ions by the aryl cations, removing MeOH molecules from the solvation shell.

Aryldiazonium ions are inherently reactive molecules that undergo a wide variety of chemical transformations that can be carried out under milder conditions, often at ambient temperature and pH levels [1,2,5,[12][13][14]. Their reactivity is frequently dominated by the loss of the N 2 moiety, leading to the formation of heterolytic products, such as phenols, haloderivatives, and ethers. Scheme 1 shows some of the most common reactions of aryldiazonium ions, including the formation of diazoethers (O-coupling), azo dye (Ccoupling) reactions, and their attachments to surfaces and nanoparticles.
In the last decades, after the pioneering work by J. Pinson et al. [15], the reductive properties of aryldiazonium salts have been exploited as a very potent method for surface functionalization [16][17][18][19][20]. The method is relatively simple, easy to process, is fast, and can be employed to functionalize massive surfaces that are either flat, or are nanomaterials of various shapes and sizes [17]. The formed surfaces are robust and resistant to heat, chemical degradation, ultrasonication, and, most importantly, the grafting of surfaces is a useful and practical approach that can be applied to a variety of conducting and insulating substrates.
Briefly, the grafting procedure comprises the formation of highly reactive aryl radicals that attack the surface and that are generated, for example, through the electrochemical reduction of ArN + 2 . Variations of the method include the reaction of generated radicals with already-grafted aryl species, leading to the formation of multilayer films [17,20]. Scheme 1B illustrates the use of ArN + 2 for the grafting of both spherical nanoparticles and flat surfaces.
Compounds 2022, 2, FOR PEER REVIEW 2 chemical degradation, ultrasonication, and, most importantly, the grafting of surfaces is a useful and practical approach that can be applied to a variety of conducting and insulating substrates. Briefly, the grafting procedure comprises the formation of highly reactive aryl radicals that attack the surface and that are generated, for example, through the electrochemical reduction of ArN + 2 . Variations of the method include the reaction of generated radicals with already-grafted aryl species, leading to the formation of multilayer films [17,20]. Scheme 1B illustrates the use of ArN + 2 for the grafting of both spherical nanoparticles and flat surfaces. Aryldiazonium ions can be easily prepared from their anilines both in situ and in the solid state [1,21], and most of them can be easily handled under ambient conditions. Nevertheless, the stability of ArN + 2 depends strongly on the nature of substituents R and counterions X − . For example, aryldiazonium chlorides are highly unstable and can be explosive above 0 °C, as well as aryldiazonium perchlorates [12]. Nowadays, most synthetically prepared aryldiazonium salts are formulated as tetrafluoroborates because of the high stability and availability of the BF − 4 anion [3,12].
In an aqueous solution, in the dark, and in the absence of reducing species, ArN + 2 undergoes a rich chemistry, comprising aromatic ipso-substitutions, N-terminal addition reactions, and O-coupling reactions, among others. However, the fate of the reactions strongly depends on the acidity of the solution. For instance, we showed, in previous dediazoniation studies [2,14,[22][23][24] that, in an aqueous acid solution and in mixed alcohol-water solvents ([H3O + ] > 10 −2 M), in the dark and in the absence of reductants, the spontaneous decomposition of aryldiazonium ArN + 2 salts proceeds through a SN1-type heterolytic mechanism, where a highly reactive aryl cation is formed, reacting with nucleophiles present in their solvation shell (dissociation + addition mechanism, DN + AN, Scheme 2). Recent dediazoniation research suggests, however, that ArN + 2 may decompose heterolytically through borderline SN1-SN2 mechanisms. Surprisingly, upon moderately decreasing the acidity, reactions involving the formation of diazohydroxides, ArN2OH, diazoethers, ArN2OR, and diazoates, ArN2O − , become competitive and may even constitute the main decomposition pathway [2]. Aryldiazonium ions can be easily prepared from their anilines both in situ and in the solid state [1,21], and most of them can be easily handled under ambient conditions. Nevertheless, the stability of ArN + 2 depends strongly on the nature of substituents R and counterions X − . For example, aryldiazonium chlorides are highly unstable and can be explosive above 0 • C, as well as aryldiazonium perchlorates [12]. Nowadays, most synthetically prepared aryldiazonium salts are formulated as tetrafluoroborates because of the high stability and availability of the BF − 4 anion [3,12]. In an aqueous solution, in the dark, and in the absence of reducing species, ArN + 2 undergoes a rich chemistry, comprising aromatic ipso-substitutions, N-terminal addition reactions, and O-coupling reactions, among others. However, the fate of the reactions strongly depends on the acidity of the solution. For instance, we showed, in previous dediazoniation studies [2,14,[22][23][24] that, in an aqueous acid solution and in mixed alcohol-water solvents ([H 3 O + ] > 10 −2 M), in the dark and in the absence of reductants, the spontaneous decomposition of aryldiazonium ArN + 2 salts proceeds through a S N 1-type heterolytic mechanism, where a highly reactive aryl cation is formed, reacting with nucleophiles present in their solvation shell (dissociation + addition mechanism, D N + A N , Scheme 2). Recent dediazoniation research suggests, however, that ArN + 2 may decompose heterolytically through borderline S N 1-S N 2 mechanisms. Surprisingly, upon moderately decreasing the acidity, reactions involving the formation of diazohydroxides, ArN 2 OH, diazoethers, ArN 2 OR, and diazoates, ArN 2 O − , become competitive and may even constitute the main decomposition pathway [2].
In this work, we analyze the effects of the solvent composition and of added electrolytes (NaCl, LiCl, and LiClO 4 ) on the esolvolytic dediazoniation of 2-, 3-, and 4-methylbenzenediazonium ions (2MBD, 3MBD, and 4MBD, respectively) in acidic MeOH/H 2 O mixtures (20% and 99.5%). The aim of the manuscript is two-fold: (1) to complement previous kinetic studies that were focused on the effects of electrolytes on short-lived In this work, we analyze the effects of the solvent composition and of added electrolytes (NaCl, LiCl, and LiClO4) on the esolvolytic dediazoniation of 2-, 3-, and 4methylbenzenediazonium ions (2MBD, 3MBD, and 4MBD, respectively) in acidic MeOH/H2O mixtures (20% and 99.5%). The aim of the manuscript is two-fold: (1) to complement previous kinetic studies that were focused on the effects of electrolytes on short-lived carbocations, particularly on the effects of the solvent composition on the solvation shell of the ipso carbon of aryldiazonium ions, and (2) to investigate if the addition of electrolytes may modify the composition of the solvation shell of aryl carbocations.
For this purpose, we determined the dediazoniation rate constants for ArN + 2 loss and for product formation, as well as the product distribution at various solvent compositions. Reported thermodynamic and kinetic data, obtained upon the solvolysis of ArN + 2 in a number of alcohol-water mixtures (MeOH, EtOH, 2,2,2-trifluoroethanol, BuOH), are consistent with the SN1 mechanism; that is, the rate-determining formation of a highly reactive aryl cation that traps the nucleophiles in its solvation shell [14,[22][23][24][25][26][27][28][29]. The major dediazoniation products are the corresponding methylphenyl ethers and cresols, and the equal amounts of products that are produced at water molar fractions of 0.34-0.36, suggesting that the aryldiazonium ions undergo preferential solvation by water, and that the preferential solvation around the ipso carbon reflects the experimental product yield obtained [2,14,22].
The rates of the reactions of stable carbocations and aryldiazonium ions with water, alcohols, and anions have been described in terms of the Ritchie's equation log(k/k0) = N+, based on the assumption that the relative reactivities of two nucleophiles are controlled by the differences in their N+ values, which are considered independent of the electrophilicities of the reaction partners. Later, Mayr et al. [30][31][32] demonstrated that the rates of these reactions can be described in terms of their electrophilicity and nucleophilicity parameters, log(k) = s(E + N), where s is a nucleophile-specific parameter. A theoretical interpretation of the physical meaning of s has been published and a comprehensive list of N and E parameters can be found elsewhere [33]. The development of nucleophilicity scales has intrigued chemists for years, and Grunwald and Winstein proposed a relationship for the solvolyses of SN1 reactions on the basis of the solventionizing power Y and a substrate-specific parameter m whose value was one for t-butyl chloride [34][35][36], log (k/kW) = mY. This equation holds for SN1 reactions, where the nucleophilic participation of the solvent in the rate-determining step is negligible [2,35].
In this work, we are particularly interested in analyzing the effects of ClO − 4 ions on solvolytic dediazoniations. Aryldiazonium perchlorates are particularly effective for the Heck palladium-catalyzed arylation of olefins when reactions are carried out in alcoholwater mixtures because of the high yields obtained and because they are cheaper reagents than those with other counterions [37]. However, cautions must be taken, because some aryl diazonium perchlorates have been reported to be explosive when prepared in the solid state [38,39]. Conversely, they can be conveniently generated in situ [37]. Perchlorate For this purpose, we determined the dediazoniation rate constants for ArN + 2 loss and for product formation, as well as the product distribution at various solvent compositions. Reported thermodynamic and kinetic data, obtained upon the solvolysis of ArN + 2 in a number of alcohol-water mixtures (MeOH, EtOH, 2,2,2-trifluoroethanol, BuOH), are consistent with the S N 1 mechanism; that is, the rate-determining formation of a highly reactive aryl cation that traps the nucleophiles in its solvation shell [14,[22][23][24][25][26][27][28][29]. The major dediazoniation products are the corresponding methylphenyl ethers and cresols, and the equal amounts of products that are produced at water molar fractions of 0.34-0.36, suggesting that the aryldiazonium ions undergo preferential solvation by water, and that the preferential solvation around the ipso carbon reflects the experimental product yield obtained [2,14,22].
The rates of the reactions of stable carbocations and aryldiazonium ions with water, alcohols, and anions have been described in terms of the Ritchie's equation log(k/k 0 ) = N + , based on the assumption that the relative reactivities of two nucleophiles are controlled by the differences in their N + values, which are considered independent of the electrophilicities of the reaction partners. Later, Mayr et al. [30][31][32] demonstrated that the rates of these reactions can be described in terms of their electrophilicity and nucleophilicity parameters, log(k) = s(E + N), where s is a nucleophile-specific parameter. A theoretical interpretation of the physical meaning of s has been published and a comprehensive list of N and E parameters can be found elsewhere [33]. The development of nucleophilicity scales has intrigued chemists for years, and Grunwald and Winstein proposed a relationship for the solvolyses of S N 1 reactions on the basis of the solvent-ionizing power Y and a substratespecific parameter m whose value was one for t-butyl chloride [34][35][36], log (k/k W ) = mY. This equation holds for S N 1 reactions, where the nucleophilic participation of the solvent in the rate-determining step is negligible [2,35].
In this work, we are particularly interested in analyzing the effects of ClO − 4 ions on solvolytic dediazoniations. Aryldiazonium perchlorates are particularly effective for the Heck palladium-catalyzed arylation of olefins when reactions are carried out in alcoholwater mixtures because of the high yields obtained and because they are cheaper reagents than those with other counterions [37]. However, cautions must be taken, because some aryl diazonium perchlorates have been reported to be explosive when prepared in the solid state [38,39]. Conversely, they can be conveniently generated in situ [37]. Perchlorate is a commercially available anion that forms salts with many cations (NH + 4 , Li + , Na + , K + , etc.). Probably the most common form of perchlorate includes ammonium perchlorate (frequently used as a solid rocket oxidant and as ignition source in fireworks) and potassium perchlorate (used in road flares and in air bag inflation systems). Other commercial perchlorate counterions include H + , Li + , Na + , K + , NH + 4 , Al 3+ , and N 2 H + 5 . Perchlorate is also formed in laboratory waste as a byproduct of perchloric acid. It is a very poor complexing agent, similar to other weak anions, such as tetrafluoroborate or trifluoromethanesulfonates (triflate, CF 3 SO − 3 ), making it very useful in metal cation chemistry [40]. The high solubility in both aqueous and non-aqueous media, together with the highly delocalized monovalent charge over the four oxygen atoms and its large volume, allows it to be widely used to adjust ionic strength in kinetic experiments. From the thermodynamic point of view, perchlorates are expected to be powerful oxidizers (E 0 = −1.229 V), but the stability of ClO − 4 in solution is governed by kinetics and not thermodynamics, and, therefore, they do not easily oxidize [40,41].
Hereafter, solution compositions are given by their percent of MeOH (by volume). Molar concentrations were calculated by ignoring the small excess volume of mixed solvents [44].

Instrumentation
UV-VIS spectra, and some kinetic experiments, were followed on a Beckman DU-640 UV-VIS or on an Agilent HP-6456 diode array spectrophotometer, both equipped with cell carriers thermostated with water from a refrigerated/heating circulator, Julabo F1 2-ED, and were attached to computers for data storage. A product analysis was carried out with the aid of a WATERS HPLC system, equipped with a model 2487 dual-λ absorbance detector, a model 717 automatic injector, a model 600 quaternary pump, and a computer for data storage. The dediazoniation products were separated with a reverse phase column (Microsorb-MV C-18 (Rainin, 25 cm length, 4.6 mm internal diameter, and 5 µm particle size) using an acidic 70/30 (v/v) MeOH/H 2 O mobile phase, containing 10 −4 M HCl. The injection volume was set at 25 µL in all runs and the UV detector was set at 220 nm. Details on the method can be found elsewhere [42,45].

Methods
Kinetic data were obtained both chromatographically and spectrophotometrically. Observed rate constants, k obs , were obtained by fitting the percentage of yield-time or absorbance-time data to the integrated first order Equation (1), where X stands for the experimental measured UV-VIS absorbance or product yields. Runs were done at T = 35 ± 0.1 • C (2MBD and 3MBD) and at T = 60 ± 0.1 • C (4MBD) with aryldiazonium ions, ArN + 2 , as the limiting reagents. The reported k obs values are the average of duplicate or triplicate experiments, with deviations lower than 7%.
Spectrophotometric kinetic data were obtained by monitoring ArN + 2 loss at a suitable wavelength to minimize interferences with other components of the solution (dediazoniation products) as much as possible. Linear variations (not shown) in the absorbance of ArN + 2 in aqueous and MeOH solutions up to [ArN found, keeping with the predictions of Beer's law. ArN + 2 solutions were prepared by dissolving the corresponding aryldiazonium salt in the appropriate acidic (HCl) MeOH/H 2 O mixtures to diminish diazotate formation [2]. Final concentrations were approximately 1.0 × 10 −4 M and [HCl] = 0.01 M. The stock ArN + 2 solutions were kept in the dark at low temperatures (T < 5 • C) to minimize their photochemical and/or spontaneous decomposition (Zollinger, 1994) and were used immediately or within a time period of less than 60 min.
Preliminary HPLC experiments showed that, in the absence of ClO − 4 , up to five decomposition products were detected to different extents. The most frequent were cresols, ArOH, and the methyl phenyl ethers (ArOMe), and, on occasion, depending on the particular experimental conditions, chlorotoluenes (when investigating Cl − dependence), as well as the reduction product, toluene (ArH), that was detected in low yields when employing high percentages of MeOH in the solvent mixture. The calibration curves for all these products were obtained by employing authentic commercial samples. Linear (cc. > 0.999) calibration absorbance-concentration plots were obtained and employed for converting HPLC peak areas into concentrations. The following equation Yield = 100 [dediazoniation product]/[ArN + 2 T ] was employed to calculate the yields of the various dediazoniation products.
When studying the effects of the perchlorate salts, a new chromatographic peak was found that was not observed in its absence, with a retention time lower than that of ArOH but higher than that of the front peak (see Figure S1, Supplementary Materials). The area of this new peak increased linearly upon the increasing [LiClO 4 ]. In dediazoniations, where sulfate ions were employed, the aryldiazonium sulfate anion, Ar-OSO − 4 was formed and could be isolated [46,47]. As the possibility of the formation of the aryldiazonium perchlorate derivative ArOClO 3 exists, which is explosive in the solid state [3,38], we made no attempts in identifying nor isolating this new product. In spite of this, the failure in identifying this new derivative does not invalidate the main conclusions of the work because: (i) the peak area is proportional to the added [LiCLO 4 ] and (ii) dediazoniation products are formed competitively and their rate of formation is the same as that of other dediazoniation products (as determined from the variations in its peak areas with time), and equal to that of ArN + 2 loss. The rates of the formation of dediazoniation products were obtained by employing a derivatization method, as described elsewhere [48]. To minimize side reactions that may occur upon the injection of ArN + 2 in the HPLC system (metal parts, solvent, etc.), TRIS buffer ([TRIS] = 0.05 M) solutions of the coupling agent 2N6S, that allows for the rapid formation of a stable azo dye, were employed [48]. The dediazoniations were quenched at convenient times, as described elsewhere [42,48]. The derivatization reaction was carried out under pseudo-first order conditions ([2N6S] > 20 [ArN + 2 ]). The final pH was adjusted to a pH of approximately 8, because naphthoxide ions are much more reactive than their protonated forms. It is not advisable to use lower acidities, because the competing reactions of aryldiazonium ions with OH − , to form diazotates, becomes significant [2].
The experimental conditions were chosen so that the coupling reaction was essentially over by the time the reagents were mixed, i.e., azo dye formation is much faster than dediazoniations (at least 100 times faster) and ArN + 2 is effectively quenched at any solvent composition. Figure 1 illustrates the determination of the rates of product formation (ArOMe, Figure 1A) and of ArN + 2 loss by monitoring the decrease in the absorbance of the azo dye formed ( Figure 1B).
Compounds 2022, 2 59 than dediazoniations (at least 100 times faster) and ArN + 2 is effectively quenched at any solvent composition. Figure 1 illustrates the determination of the rates of product formation (ArOMe, Figure 1A) and of ArN + 2 loss by monitoring the decrease in the absorbance of the azo dye formed ( Figure 1B).

Spontaneous Dediazoniation of 2-, 3-, and 4-Methylbenzenediazonium Ions: Effects of Solvent (MeOH/H2O) Composition on the Observed Rate Constant, kobs
The effects of the solvent composition on the observed rate constant kobs for the spontaneous dediazoniation of 2MBD, 3MBD, and 4MBD were explored by modifying the percentage of MeOH in the reaction mixture, as shown in Figure 2. Solvolytic rate constants kobs increased smoothly at low percentages of MeOH, but more drastically at high percentages of methanol. The kobs values at 0% MeOH, kobs = 6 × 10 −4 s −1 (2MBD), 8 × 10 −4 s −1 (3MBD), and 9.5 × 10 −4 s −1 (4MBD) aligned with the reported values obtained by different techniques, including N2 evolution [49] at pH = 1.6-1.8, as well as HPLC and VIS-UV spectrophotometry [14]. The increase in kobs, upon changing the methanol content, was modest, less than two-fold, and much lower than those reported in other solvolytic reactions. It is, however, aligned with literature reports that indicate that the rates of heterolytic dediazoniation of a number of arenediazonium ions vary by a factor of only 9 in 19 solvents [1].

Spontaneous Dediazoniation of 2-, 3-, and 4-Methylbenzenediazonium Ions: Effects of Solvent (MeOH/H 2 O) Composition on the Observed Rate Constant, k obs
The effects of the solvent composition on the observed rate constant k obs for the spontaneous dediazoniation of 2MBD, 3MBD, and 4MBD were explored by modifying the percentage of MeOH in the reaction mixture, as shown in Figure 2. Solvolytic rate constants k obs increased smoothly at low percentages of MeOH, but more drastically at high percentages of methanol. The k obs values at 0% MeOH, k obs = 6 × 10 −4 s −1 (2MBD), 8 × 10 −4 s −1 (3MBD), and 9.5 × 10 −4 s −1 (4MBD) aligned with the reported values obtained by different techniques, including N 2 evolution [49] at pH = 1.6-1.8, as well as HPLC and VIS-UV spectrophotometry [14]. The increase in k obs , upon changing the methanol content, was modest, less than two-fold, and much lower than those reported in other solvolytic reactions. It is, however, aligned with literature reports that indicate that the rates of heterolytic dediazoniation of a number of arenediazonium ions vary by a factor of only 9 in 19 solvents [1].

Effects of Added Electrolytes on Dediazoniation Rate Constants
The effects of electrolytes ([NaCl] = 0-1 M, [LiCl] = 0-1 M, and [LiCLO − 4 ] = 0-1.5 M) on k obs were determined at two representative solvent compositions (20% and 99.5% MeOH), as seen in Figure 3. At 20% MeOH, k obs values, in the absence of salt, were similar to those in Figure 1. The addition of NaCl, LiCl, or LiClO 4 did not have a significant effect on k obs and the values remained essentially constant. However, when the percentage of MeOH increased to 99.5%, the addition of NaCl and LiCl (up to 1.5 M) did not significantly change k obs , but, upon increasing [LiClO 4 ], k obs values decreased by approximately 40%. The observed decrease in k obs values with the presence of ClO 4 ions, though somewhat modest, was unexpected and quite significant because no changes in k obs were found in the presence of other salts and the decrease in k obs was only detected at high percentages of MeOH. This is an important decrease that deserves further investigation, because we noted that k obs values only had a two-fold change when going from 0 to 100% MeOH, as seen in Figure 3.

Effects of Added Electrolytes on Dediazoniation Rate Constants
The effects of electrolytes ([NaCl] = 0-1 M, [LiCl] = 0-1 M, and [LiCLO − 4 ] = 0-1.5 M) on kobs were determined at two representative solvent compositions (20% and 99.5% MeOH), as seen in Figure 3. At 20% MeOH, kobs values, in the absence of salt, were similar to those in Figure 1. The addition of NaCl, LiCl, or LiClO4 did not have a significant effect on kobs and the values remained essentially constant. However, when the percentage of MeOH increased to 99.5%, the addition of NaCl and LiCl (up to 1.5 M) did not significantly change kobs, but, upon increasing [LiClO4], kobs values decreased by approximately 40%. The observed decrease in kobs values with the presence of ClO4 -ions, though somewhat modest, was unexpected and quite significant because no changes in kobs were found in the presence of other salts and the decrease in kobs was only detected at high percentages of MeOH. This is an important decrease that deserves further investigation, because we noted that kobs values only had a two-fold change when going from 0 to 100% MeOH, as seen in Figure 3. To obtain further insights into the dediazoniation process, we employed the chromatographic technique, as illustrated in Figure 4, to determine kobs for product formation, in the absence and in the presence of added electrolytes, at two selected solvent compositions (20 and 99.5% MeOH). The kobs values for product formation were the same as those obtained spectrophotometrically for ArN + 2 loss, confirming that products are formed competitively, in keeping with the predictions of the DN + AN mechanism shown in Scheme 2A. To obtain further insights into the dediazoniation process, we employed the chromatographic technique, as illustrated in Figure 4, to determine k obs for product formation, in the absence and in the presence of added electrolytes, at two selected solvent compositions (20% and 99.5% MeOH). The k obs values for product formation were the same as those obtained spectrophotometrically for ArN + 2 loss, confirming that products are formed competitively, in keeping with the predictions of the D N + A N mechanism shown in Scheme 2A.
To obtain further insights into the dediazoniation process, we employed the chromatographic technique, as illustrated in Figure 4, to determine kobs for product formation, in the absence and in the presence of added electrolytes, at two selected solvent compositions (20 and 99.5% MeOH). The kobs values for product formation were the same as those obtained spectrophotometrically for ArN + 2 loss, confirming that products are formed competitively, in keeping with the predictions of the DN + AN mechanism shown in Scheme 2A.  Figure 5 shows the effects of the solvent composition on the product distribution of 3-and 4MBD in the absence of added electrolytes. Only the heterolytic products (cresol and methyl phenyl ethers) were formed in significant yields, and the formation of the reduction product Ar-H was only detected in highly alcoholic solutions (4MBD) but its yield was very low when compared with those of heterolytic products; therefore, such a mechanism (homolytic) can be neglected. In all cases, the quantitative conversion to products was achieved in all composition ranges. The results are in agreement with published data [30,32,34].  Figure 5 shows the effects of the solvent composition on the product distribution of 3-and 4MBD in the absence of added electrolytes. Only the heterolytic products (cresol and methyl phenyl ethers) were formed in significant yields, and the formation of the reduction product Ar-H was only detected in highly alcoholic solutions (4MBD) but its yield was very low when compared with those of heterolytic products; therefore, such a mechanism (homolytic) can be neglected. In all cases, the quantitative conversion to products was achieved in all composition ranges. The results are in agreement with published data [30,32,34]. To analyze the effects of added electrolytes, we selected two methanol compositions, 20% and 99.5% MeOH. At a low methanol content, the addition of salts (NaCl and LiClO4) up to 1.5 M had a negligible effect on the production distribution, as illustrated in Figure  6. However, this was not the case at high percentages of MeOH, Figure 7. To analyze the effects of added electrolytes, we selected two methanol compositions, 20% and 99.5% MeOH. At a low methanol content, the addition of salts (NaCl and LiClO 4 ) up to 1.5 M had a negligible effect on the production distribution, as illustrated in Figure 6. However, this was not the case at high percentages of MeOH, Figure 7. To analyze the effects of added electrolytes, we selected two methanol compositions, 20% and 99.5% MeOH. At a low methanol content, the addition of salts (NaCl and LiClO4) up to 1.5 M had a negligible effect on the production distribution, as illustrated in Figure  6. However, this was not the case at high percentages of MeOH, Figure 7.   At 99.5% MeOH, in the presence of LiCl, the Ar-Cl derivative was detected, in addition to Ar-OH and Ar-OMe, and an increase in [LiCl] of up to 1.5 M had a negligible effect on the product distribution, as seen in Figure 7A,C, so that the quantitative conversion to products was obtained. As expected, when using LiClO4 instead of LiCl, the At 99.5% MeOH, in the presence of LiCl, the Ar-Cl derivative was detected, in addition to Ar-OH and Ar-OMe, and an increase in [LiCl] of up to 1.5 M had a negligible effect on the product distribution, as seen in Figure 7A,C, so that the quantitative conversion to products was obtained. As expected, when using LiClO 4 instead of LiCl, the Ar-Cl derivative was not detected but, surprisingly, a significant reduction in the yields of Ar-OMe was detected, as seen in Figure 7B,D. We note that the total yield decreases because of the presence of an unidentified dediazoniation product, whose yield could not be computed because we made no attempts to fully identify the new product, mainly for safety reasons (see Section 2).

Discussion
Solvolytic dediazoniations have long been studied, and there is now a substantial body of knowledge on the reactions. For instance, the sensitivity of dediazoniations towards solvent polarity has been analyzed by employing the Winstein-Grunwald equation [26,27], yielding slopes for 2MBD, 3MBD, and 4MBD of m = −0.026, −0.018, and −0.058, respectively. These values are quite low and reflect the astonishing insensitivity of dediazoniations to the nature of the solvent [1]. The low values are interpreted on the grounds of similarities in the structure and the charge allocation between the parent aryldiazonium ion and the corresponding aryl cation [14,50,51].
The selectivity values for a number of aryldiazonium ions have also been obtained, assuming that the nucleophilic attack on the carbocation is under kinetic control. In aqueous solution, aryldiazonium ions have a small selectivity against reacting nucleophiles, compared to water, typically ranging from 0.4 to 6 [46], following the order Br − > Cl − > SO 2− 4 > H 2 O. Such values are orders of magnitude lower than those observed for nucleophiles competing with water in reactions with stabilized carbocations [14,52,53], and are essentially constant with solvent composition. Table 1 shows the selectivity values for 2-, 3-, and 4-MBD. Such low values are consistent the formation of highly reactive aryl cations and with the preassociation of the stepwise mechanism, as shown in Scheme 1A. Table 1. Selectivity values for 2-, 3-, and 4MBD. Data from references [14,22,54].  Figure 2. Moreover, barriers for the capture of carbocations by the solvent [55] are sufficiently small, so that the product distribution reflects the solvent distribution in the first solvation shell of the reactant, suggesting, therefore, that the solvation of the ground state ArN + 2 is essentially the same as that in the proximity of the transition state. Thus, at low MeOH content, the presumed aryl cations are mostly solvated by water molecules, and a relatively modest increase in the concentrations of NaCl, LiCl, or LiClO 4 (in comparison to that of water) does not have significant effects on both the dediazoniation rate constants (Figure 3), and on product distributions ( Figure 6).

Methylbenzenediazonium Ions S Cl
The sensitivity of dediazoniations to changes in the solvent polarity can be illustrated by means of a Winstein-Gruwald plot, as shown in Figure 8, where a linear relationship between log(k/k w ) with the Y parameter is found, with slopes of m = −0.032 ± 0.001 (2MBD), m = −0.037 ± 0.001 (3MBD), and m = −0.072 ± 0.003 (4MBD), consistent with the low selectivity of aryldiazonium ions to solvent effects [52,56]. This low sensitivity can be attributed to the similarity in the structure and charge distribution of the parent aryldiazonium ion, compared to that of the corresponding aryl cation.
Surprisingly, when dediazoniations are carried out in solutions with high concentrations of MeOH, a different behavior is observed. The addition of NaCl or LiCl does not modify kobs values, as seen in Figure 3D,E, and the analysis of the product distribution confirms the expected formation of the chlorobenzene derivatives. However, upon the addition of LiClO4, both kobs ( Figure 3F) and the yields of the corresponding methyl phenyl ethers (ArOMe, Figure 7B,D) decrease. We note that chromatograms do not show the formation of the reduction products (toluenes, Ar-H) in a large extent and, thus, we can safely presume that the mechanism of the reaction does not change in the presence of LiClO4. Thus, the variations in the yields of Ar-OMe can be attributed to the replacement of MeOH molecules in the solvation shell by ClO − 4 ions, presumably leading to the formation of the potentially explosive (in the solid state) aryldiazonium perchlorates.
Our hypothesis regarding perchlorate ions modifying the solvation shell of aryldiazonium ions seems to be supported by the results of Cruz et al. [58], who carried out a molecular dynamic study of dediazoniations and calculated the local concentrations of solvents around diazonium ions, concluding that, in the absence of salts, the local solvent composition varied linearly on the molar fraction of water in methanol/water mixtures, although they found non-linear variations for other solvent mixtures. The same authors also found that the calculated number of solvent molecules around the aryldiazonium cation can predict the product distribution when preferential solvation is considered. However, results must be taken with some caution because of the failure to identify the new product formed in the presence of LiClO4.
The rates of dediazoniations with uncharged nucleophiles (such as MeOH or H2O) are hardly affected by the nature of the solvent, as shown in Figure 2, because the electric charges are neither destroyed nor created in the rate-determining step. In fact, the rates of heterolytic dediazoniations have been reported to vary only by a factor of 9 when carried out in 19 solvents [1]. Thus, the low variation in kobs with [MeOH] suggests that the solvation of the ground-state is similar to the proximity of the transition state; otherwise, unimolecular reactions, where the nucleophilic attack of the solvent is rate-determining, would lead to a strong dependence of kobs on nucleophile concentration, which is not observed. The rates of the nucleophilic attack on aryl cations have been reported to be close to the diffusion control limit (~10 9 M −1 ·s −1 ) and the preassociation of the nucleophile with the aryl cation does not account for much of the trapping [1,2,46]. Surprisingly, when dediazoniations are carried out in solutions with high concentrations of MeOH, a different behavior is observed. The addition of NaCl or LiCl does not modify k obs values, as seen in Figure 3D,E, and the analysis of the product distribution confirms the expected formation of the chlorobenzene derivatives. However, upon the addition of LiClO 4 , both k obs ( Figure 3F) and the yields of the corresponding methyl phenyl ethers (ArOMe, Figure 7B,D) decrease. We note that chromatograms do not show the formation of the reduction products (toluenes, Ar-H) in a large extent and, thus, we can safely presume that the mechanism of the reaction does not change in the presence of LiClO 4 . Thus, the variations in the yields of Ar-OMe can be attributed to the replacement of MeOH molecules in the solvation shell by ClO − 4 ions, presumably leading to the formation of the potentially explosive (in the solid state) aryldiazonium perchlorates.
Our hypothesis regarding perchlorate ions modifying the solvation shell of aryldiazonium ions seems to be supported by the results of Cruz et al. [58], who carried out a molecular dynamic study of dediazoniations and calculated the local concentrations of solvents around diazonium ions, concluding that, in the absence of salts, the local solvent composition varied linearly on the molar fraction of water in methanol/water mixtures, although they found non-linear variations for other solvent mixtures. The same authors also found that the calculated number of solvent molecules around the aryldiazonium cation can predict the product distribution when preferential solvation is considered. However, results must be taken with some caution because of the failure to identify the new product formed in the presence of LiClO 4 .
The rates of dediazoniations with uncharged nucleophiles (such as MeOH or H 2 O) are hardly affected by the nature of the solvent, as shown in Figure 2, because the electric charges are neither destroyed nor created in the rate-determining step. In fact, the rates of heterolytic dediazoniations have been reported to vary only by a factor of 9 when carried out in 19 solvents [1]. Thus, the low variation in k obs with [MeOH] suggests that the solvation of the ground-state is similar to the proximity of the transition state; otherwise, unimolecular reactions, where the nucleophilic attack of the solvent is rate-determining, would lead to a strong dependence of k obs on nucleophile concentration, which is not observed. The rates of the nucleophilic attack on aryl cations have been reported to be close to the diffusion control limit (~10 9 M −1 ·s −1 ) and the preassociation of the nucleophile with the aryl cation does not account for much of the trapping [1,2,46].
A different situation is found when charged nucleophiles are present in the solvation shell, as they may distort the charge distribution, compared to that of neutral nucleophiles. The Mayr's reactivity scale is certainly useful to predict whether an electrophile/nucleophile reaction can be expected to take place at room temperature, or to predict the selectivity of competing nucleophiles. The rate constants of electrophilenucleophile combination reactions are mostly dependent on four factors: nucleophilicity, electrophilicity, temperature, and solvent. Strictly, it is not possible to separate these four factors, mainly because the values of the electrophilicity and nucleophilicity parameters are usually linked to the type of solvent, whose physical properties may change with changing temperatures. Nucleophilicity scales may also be affected by changes in temperature [33,59]. However, to our knowledge, an all-embracing theory of electrophile-nucleophile reactions is still not in sight, and further work on the effects of electrolytes on ionic reactions is needed.