The specific rates of acid formation were determined in 24 solvents at 25.0 °C. The solvents consisted of methanol and ethanol, and binary mixtures of water with methanol, ethanol, acetone, 2,2,2-trifluoroethanol (TFE), or HFIP, plus binary mixtures of TFE with ethanol and two values in 97%, 90% HFIP were measured at 40.0 °C. From literature values for the specific rates of solvolysis at several other temperatures, the Arrhenius Equation was used to calculate values at 25.0 °C for solvolyses in water [46] and 99.3% formic acid [47].

The experimental specific rates at 25.0 °C, the two pairs of calculated values, the previously published specific rates at 40.0 °C together with the two additional specific rates in 97% HFIP and 90% HFIP at this temperature, and the N_T [32,33] and the Y_Cl values [30,41,43,48,49] are reported in Table 1. In two instances, the experimental rate values were in good agreement with the literature rate values [50,51]. Also contained in Table 1 are percentage values at 40.0 °C for the experimental infinity titer relative to the titer that would have been observed if all reaction had proceeded with acid formation. The deficit indicates the percentage of reaction proceeding with isopropyl chloride formation.

There have been previous studies of the solvolysis of 1 in a few of the solvents listed in Table 1. Leimu [50] studied the methanolysis of a series of chloroformate esters, including the isopropyl ester, and found the specific rates of solvolysis to be in the order: CH₃OCOCl > CH₃CH₂OCOCl ~ CH₃CH₂CH₂OCOCl > 1. The value reported for the solvolysis of 1 at 25.0 °C is in excellent agreement with the value in Table 1. The mechanism was not considered but the ordering is that to be expected for bimolecular attack by solvent rather than a rate-determining ionization. A similar ordering was also observed for the ethanolyses [51], and an addition-elimination (association-dissociation) mechanism was proposed; the value for ethanolysis of 1 at 25.3 °C is in good agreement (Table 1) with our value at 25.0 °C.

There have also been studies in solvents of considerably higher ionizing power: water [46], 35% acetone [47], and formic acid [47]. Queen studied the hydrolyses of methyl, ethyl, propyl, and isopropyl chloroformates. At a given temperature, the specific rates of hydrolysis in 100% water were found to be in the order: CH₃OCOCl > CH₃CH₂OCOCl ~ CH₃CH₂CH₂OCOCl < 1. This differs from the ordering observed [50,51] in the alcoholyses in that there is now an increase in going to the isopropyl ester solvolysis. A proposed change from bimolecular to unimolecular mechanism was supported by the observations for the isopropyl chloroformate solvolysis of a considerably more positive entropy of activation and a lower solvent isotope effect than the very similar values observed for the methyl and ethyl esters.

The ordering observed in water was also observed [47] in 35% acetone (65% water) and in 99% formic acid, with a seven-fold faster reaction for 1 than for ethyl chloroformate in the aqueous acetone mixture, increasing to a 70-fold faster reaction in formic acid. It was suggested that both of the esters react by the ionization pathway in formic acid. In support, a recent estimate [12] suggests that the formolysis of ethyl chloroformate proceeds by about 10% addition-elimination and 90% ionization.

The correlations carried out in earlier studies, comparing methyl, ethyl, and isopropyl chloroformate solvolyses, have strongly indicated that the mechanism for 1 is solvent dependent, with a bimolecular association-dissociation pathway favored in pure alcohols, and an ionization pathway favored in the water-rich solvents and in formic acid. In the present investigation we carry out a systemic study of the effect of solvent variation, with the inclusion of solvents rich in fluoroalcohol (TFE and HFIP), allowing a very thorough investigation of the region within which the ionization pathway is expected to operate. Recently, there has been an interesting study considering the relationship between solvolysis rates in 97% TFE for carboxylic and sulfonic acid chlorides and the heterolytic bond dissociation enthalpies for transfer of chloride ion to the acetyl cation [28].

For a number of haloformate esters [1,16,52–55], a consideration of the F:Cl rate ratio has provided some of the best evidence in favor of the addition step within an association–dissociation (addition– elimination) mechanism being rate determining. Since the C–F bond is much stronger than the C–Cl bond, ratios of well below unity would have been anticipated if the carbon–halogen bond was appreciably broken at the transition state of the rate determining step. In contrast, if the addition-step is rate-determining, values close to unity (and frequently above it), reflecting a large electron deficiency at the carbonyl carbon of a haloformate [16] incorporating chlorine are frequently observed. The k_F/k_Cl ratios reported [54] for isopropyl fluoroformate and chloroformate at 40.0 °C in non-fluoralcohol containing solvents range from a low of 0.2 in pure ethanol to 2.4 in 70% methanol. For these two substrates the common aqueous fluoroalchohol (70% TFE) has a k_F/k_Cl value of 0.067. The low ratio in 70% TFE follows from the solvolysis of the fluoroformate being by the addition-elimination pathway [54] but this pathway constituting only a minor component in the corresponding solvolysis of the chloroformate [13], which is dominated by the superimposed ionization pathway.

In Table 2 details are given as to how the experimental specific rates of reaction for the solvolysis of 1 at 40.0 °C and 25.0 °C, are corrected for contributions from the ionization pathway leading to an estimate of the contribution from the addition-elimination pathway. The specific rates reported in Table 1, have been analyzed using Equations 1 and 2, and these results are reported in Table 3. Previously reported analyses of methyl chloroformate [12], ethyl chloroformate [10], 4 [7,21], 3 [5], and phenyl chlorodithioformate [21,24], are reported in Table 4, together with new analyses of the data previously presented [4,37] for 2

Use of Equation 1 with all 26 available data points at 40.0 °C leads to a fair correlation with an m value of 0.33, and a value of 0.31 is obtained for the 24 data points at 25.0 °C. Using Equation 2 for the data at 40.0 °C, values are obtained of 0.21 for l and 0.44 for m, and the F-test value falls modestly from 130 to 100. Similarly analysis of data at 25.0 °C yields a value of 0.14 for l, 0.40 for m (Figure 2), and the F-test fell from 127 to 71. Since earlier work [46,47] had suggested a duality of mechanism for the solvolyses of isopropyl chloroformate, the fairly good one-term analysis and the low value for l in the two-term analysis suggests that, for the majority of the solvent systems, the ionization mechanism is dominant.

Accordingly, it was felt that it would be safe to assess the correlation parameters for the ionization mechanism using specific rates in the seven most highly ionizing solvents: three TFE-H₂O mixtures, two HFIP-H₂O mixtures, H₂O, and HCOOH. It can be seen from the two entries in Table 3 that the two-term Equation gives the best correlation, with values (for data at 40.0 °C), of 0.21 for l and 0.58 for m; and 0.12 for l and 0.60 for m (for data at 25.0 °C). The l and m values barely changes on inclusion of the four TFE-EtOH mixtures and are in reasonable agreement with others believed to be for ionization reaction in solvolyses of chloroformate esters. The low l value suggests that solvation involved is at the incipient alkyl carbocation rather than at the acyl carbon. This view is, however, inconsistent with the conclusions reached by Green and Hudson [56] that the solvolysis of secondary alkyl chloroformates proceed via a carboxylium ion (ROCO⁺) intermediate. They found that the rates of formolysis and hydrolysis in aqueous acetone of a series of cycloalkyl chloroformates were slightly larger than the corresponding solvolysis of 1 and increased steadily as one went from five- to eight-membered rings. This is a different ordering to the solvolysis of the cycloalkyl tosylates, where the rate order C₅>C₆<C₇<C₈ was established and ascribed to internal strain effects [57]. This difference led to the postulate [56] that a rate-determining formation of ROCO⁺, rather than R⁺, was involved in the chloroformate ester solvolysis. It is possible, even if the ionization is indeed to R⁺, that the I-strain effects are not dominant when the transition state is earlier than for the acetolyses of the tosylates, but clearly additional studies are needed in order to give a more detailed picture of the ionization process.

At 40.0 °C, for the 10 solvents that can strongly hydrogen bond (nine fluoroalcohols and formic acid), values are obtained of 0.05 for l (0.67 probability that the lN_T term is statistically insignificant) and 0.41 for m, with a correlation coefficient of 0.984 and F-test value of 105. The F-test value improves significantly to 232 using the one-term Equation, and a low m value of 0.37 is obtained. A similar trend is observed for the data set at 25.0 °C. In this instance for the 12 fluoroalcohols and formic acid, analyses using Equation 2 results in a value of 0.05 for l (0.66 probability that the lN_T term is statistically insignificant), a value of 0.43 for m, and a F-test value of 82. The F-test value improves significantly to 175 with Equation 1, and a value of 0.40 is obtained for m.

The low m values observed at the two experimental temperatures of 1 are reminiscent of the behavior of 2 and 3, where the solvolysis-decomposition correlates well with the Equation 1, with an m value of 0.57 for 2, and 0.47 for 3 (Table 4). A low m value of 0.46 (using Y_OTs values [30]) was also reported for the solvolyses of 2-adamantyl azoxytosylate, which similarly gives solvolysis and decomposition products, after loss of N₂O [58]. It was suggested [4, 5, 37, 58] that these low m values are a feature of the loss of the small molecule (CO₂ or N₂O) during the ionization-carbocation capture process. For 2 there is a 0.71 probability and for 3, a 0.70 probability, that the lN_T term is statistically insignificant.

The similarity in l and m values for 1 and 3 suggest that a very good direct linear relationship exists between their specific rates of solvolysis, which is further substantiated by an inspection of the plot shown in Figure 3 of log (k/k_o) values for 1 against those for 3, with a correlation coefficient of 0.945, F-test value of 132, slope of 0.68 ± 0.06, and an intercept of −0.16 ± 0.05.

The low m value for the ionization pathway, similar to that for the bimolecular pathway, means that the division of the solvolyses into the two mechanistic categories is not as clear-cut as it was for EtOCOCl [10], PhSCOCl [21,25], and PhSCSCl [21,24]. The solvolysis of 4 (l = 1.66; m = 0.56) and PhSCSCl (l = 0.69; m = 0.95) can be taken as models for mechanisms involving addition-elimination and ionization without fragmentation, respectively. In Table 2 we report the experimental specific rates of reaction as corrected for the calculated specific rates for the ionization pathway, obtained using the l, m, and c values from Table 3 and the N_T and Y_Cl values from Table 1. These (k − k_i) values are then used to calculate the correlation parameters for the addition-elimination pathway in the nine solvents for which it dominates (Table 3). The l value of 1.35 ± 0.22 at 40.0 °C, and 1.01 ± 0.26 at 25.0 °C are approximately similar to the value of 1.66 ± 0.05 for 3 and the addition-elimination pathway values of 1.59 ± 0.0.09 for MeOCOCl solvolysis and 1.56 ± 0.09 for EtOCOCl solvolysis. The higher standard error results from the much narrower range of operation of the mechanism for the solvolysis of 1. Indeed, the similarity in character of the nine solvents involved would be expected to lead to an appreciable degree of multicollinearity when Equation 2 is applied to the data. Minor changes in specific rate values can then lead to relatively large changes in sensitivity values.

Only one solvent (20T-80E) has such a well-balanced component from each mechanism that it does not appear in each correlation. The remaining 16 solvents at 40.0 °C give a correlation (Table 3) with parameters very similar to those for the seven highest ionizing power solvents (l = 0.28; m = 0.59), consistent with the previously expressed belief that the ionization pathway is dominant in the majority of the studied solvents. Both the l and m values are lower than for the solvolyses of PhSCSCl, suggesting an earlier transition state.

An alternative, and more gentle way of investigating the kinetic effect of solvent variation is by studying the kinetic solvent isotope effect (KSIE), usually involving replacement of hydrogen by deuterium. In his study of the hydrolysis of several chloroformate esters, Queen [46] studied the KSIE when H₂O was replaced by D₂O. The effect is usually considered in terms of the k_H2O/k_D2O ratio. For methyl, ethyl, and phenyl esters, he obtained very similar specific rate ratios of 1.89 (at 25.0 °C), 1.82 (at 25.0 °C), and 1.79 (at 7.5 °C). For 1, the specific rate ration fell to 1.25 (at 25.0 °C). This was considered to reflect a change from a bimolecular process to a unimolecular process. This finding is nicely consistent with the present study, where an analysis indicates that, for the hydrolysis in 100% water, essentially all of the reaction proceeds by the ionization mechanism (Table 2).

The kinetic runs with addition of the neat liquid substrate were carried out using carefully measured amounts of substrate and it is possible to compare the experimental infinity titers with the theoretical values. A comparison by Queen for the reaction in water [46] has previously given a value of 98%, which would correspond to 2% isopropyl chloride formation. The values obtained are reported in Table 1. In 100%–60% methanol and 100%–50% ethanol, we also observe fairly close to the theoretical value for 100% solvolysis, with values in the range of 87 ± 5% to 97 ± 1%. Values were slightly lower in 90%–60% acetone, with an acid production range of 78 ± 3% to 86 ± 5%. Probably, a large, relatively inert acetone component to the solvent increases the probability that the isopropyl carbocation will react with the counterion, rather than with a solvent molecule. Similarly, in solvents rich in TFE (97%–70%), the solvent is of reduced nucleophilicity and lower values are observed, with the lowest value for all the solvents studied being 67 ± 1% in 97% TFE. It is probable that even lower values would have been obtained in the HFIP-H₂O mixtures, but, because of the relatively fast reaction, we concentrated on rapid mixing rather than accurate measurement of the amount of added substrate. Even with accurate measurement, an appreciable amount of product formation would occur, in these solvents, under the inhomogeneous conditions present during the mixing process.