Study of Kinetics , Equilibrium and the Influence of Steric Effects on Proton-Transfer in the Reactions of 2 , 2 , 4-and 2 , 6-Substituted Anilines with 2-Phenoxy-3 , 5-dinitropyridine in DMSO

Kinetic and equilibrium results for the reactions of 2-phenoxy-3,5dinitropyridine (1), with a series of 2, 2, 4and 2, 6substituted anilines (2a-f), in the presence of DABCO in DMSO are reported. The reactions yield the 2anilino derivatives (5), without the accumulation of intermediates. Kinetics studies are compatible with a two-step mechanism involving initial nucleophilic attack by amine at the ring carbon substituted by phenoxy group followed by either base-catalyzed or uncatalyzed conversion to the product. The basecatalyzed pathway is likely to involve rate-limiting proton-transfer from the zwitterionic intermediate to base. This work indicates a steric effect to proton transfer in reactions involving 2, 6-disubstituted anilines. The results were compared with those for reactions of 1, 3, 5-trinitrobenzene with anilines.


Introduction
The Kinetic studies of nucleophilic substitution reactions of aromatic substrates have been the subject of several excellent reviews and books [1][2][3][4] and are still an area of active research [5][6][7][8][9] .The presence of electron-withdrawing ring-substituents such as the nitro group strongly accelerates substitution and ring nitrogen atoms have also been found to exert a powerful activating effect 7 .However ring nitrogen ortho to the substitution position has generally been found to be less effective than a corresponding nitro group [8][9][10][11][12] .
In a previous study, the reactions of 1,3,5-trinitrobenzene which are characterized by the absence of good leaving groups with anilines in DMSO in the presence of DABCO have been shown to yield anionic σ-adducts.Kinetic and equilibrium studies 13 are compatible with a two-step process involving initial nucleophilic attack by amine at an unsubstituted ring position followed by proton transfer from the zwitterionic intermediate to base.

BASIM H. ASGHAR
In agreement with the classic work of Orvik an Bunnett 14 , the results for ethyl 2,4,6trinitrophenyl ether indicated that substitution involves the specific base-general acid catalysis mechanism, SB-GA, in which leaving group expulsion is the overall rate-limiting step.However, the phenoxy group is a considerably better leaving group than the ethoxy group and the observation of base catalysis in reactions of phenyl aryl ethers was best explained in terms of rate-limiting proton transfer from a zwitterionic intermediate to base 15,16 .
More recently, kinetic and equilibrium results have been reported for the reactions of 2phenoxy-3,5-dinitropyridine (1), with some 4-substituted anilines in the presence of DABCO, in DMSO 17 .
In this paper, kinetic and equilibrium results are reported for the reactions of 1 with a series of 2, 2, 4-and 2, 6-substituted anilines (2a-f), carrying substituents close to the reaction centre, in DMSO in the presence of DABCO (Scheme 1).The results are compared with those reported in earlier studies for the reaction of 1, 3, 5-trinitrobenzen with anilines 18 .The pK a values for the substituted anilinium ions in DMSO were available from previous work using the proton-transfer equilibrium with 2, 4-dinitrophenol 18 .
UV-visible spectra and kinetic measurements were made with Shimadzu UV-2101 PC.All measurements were made at 25 o C. First order rate constants, precise to ±3%, were evaluated using standard methods.NMR data of compounds 5a-c are as follow:

Kinetic and equilibrium studies
Kinetic measurements of the reactions of 1 with substituted anilines (2a-f), were generally made in the presence of DABCO and DABCO hydrochloride, 0.01 mol dm −3 .The absorption maxima of the products formed is ca 380 nm.The concentration of 1 was kept at 5 × 10 −5 mol dm −3 and was very much lower than that of the other components, one of the substituted anilines (2a-f) and DABCO.Under these conditions, accurate first order kinetics were observed and the variation in value of the rate constant with aniline and DABCO concentrations was examined.Measurements were also made in the absence of DABCO and plots of the second order rate constant, k obs /[aniline], versus aniline concentration were linear with positive intercepts.
These results are interpreted in terms of the processes shown in Scheme 1.It is known 15-18,20-21 that phenoxide is a considerably better leaving group than ethoxide, by a factor of ca. 10 6 .The failure to observe 4, the intermediate on the substitution pathway, may be attributed to its rapid decomposition by loss of phenoxide.The assumption that 3 may be treated as a steady-state intermediate leads to the rate expression of eq. ( 1), where k An and k DABCO represent for the respective bases 16 .
The presence of a phenoxy group is not expected to drastically affect the value of K 1 for formation of zwitterions 23 .The k 2 step is likely to involve intramolecular proton transfer from nitrogen to oxygen coupled with carbon-oxygen cleavage.Leaving group expulsion is part of the rate-limiting step here.
Values obtained for K 1 k DABCO , K 1 k 2 and K 1 k An are summarised in Table 2 together with pK a values, measured in DMSO, for the conjugate acids of the anilines.The present work is concerned with anilines (2a-f) carrying substituents close to the reaction centre.Figure 1 & 2 show logarithmic plots of the values of log K 1 k DABCO and log K 1 k An versus the pK a values of the corresponding anilinium ions.This shows that for anilines (2a-b) which have groups at ortho-positions values are considerably below the lines defined by the other substituents.These deviations are likely to result from steric effects.These might involve either steric hindrance to nucleophilic attack, which would affect values of K 1 , or steric hindrance to proton transfer, which would affect values of k DABCOH + and also k DABCO .The observation that both values of K 1 k DABCO and K 1 k An values of are lowered in 2a-b indicates that the major steric effect is to the proton transfer step from the zwitterionic intermediate 3 to DABCO.Values of K 1 k An decrease much more dramatically going from 2c to 2f.This indicates that the k An process is far more favourable with 2, 4-dimethylaniline than with 2cyanoaniline.A possible explanation is that the proton-transfer equilibrium is not strongly thermodynamically favoured.Hence as the basicity of the aniline decreases the rate constant for the process is reduced as shown in Scheme 2.
The values of K 1 k An is higher than the corresponding values of K 1 k DABCO .This is likely to result from a reduction in the value of k An in the reaction of 1 since the proton transfer process involved is less thermodynamically favourable than in the corresponding reaction involving 1,3,5-trinitrobnzene.It should be noted that since proton-transfer is rate-determining in all these reactions, it is not possible to obtain values for the rate constants k 1 and k -1 relating to formation of the zwitterionic intermediates.

Conclusions
In comparing reactions of anilines (2a-f) with each of 1 and 1,3,5-trinitrobenzene, it was noted as shown in Table 3 that the product K 1 k DABCO has a higher value for the reaction of 1,3,5trinitrobenzene than with 1 (ratio is 100/1).The predominant factor here, as discussed previously 16 will be the higher value of k DABCO associated with the lower steric hindrance to proton transfer when reaction occurs at an unsubstituted ring position.The value of K 1 must also be considerably higher for 1,3,5-trinitrobenzene than for 1.In 1 there is some relief of steric strain more than in 1,3,5-trinitrobenzene and less activation as ring N replaces NO 2 .It is difficult to quantity these factors, but of course overall the order turns out to be 1,3,5-trinitrobenzene >1.
The fact that the product K 1 k DABCO has a higher value for the reaction of 1,3,5trinitrobenzene indicates that also, the zwitterions for reaction 1,3,5-trinitrobenzene with anilines are more acidic than zwitterions 3. Apparently the negatively charged 1,3,5trinitrobenzene moiety in zwitterions is more electron-withdrawing than the corresponding moiety in 3. Independent support for this idea comes from the observation 24 that, 2,4,6trinitrodiphenylamine, pK a 8.20 is more acidic than 2-anilino-3,5-dinitropyridine, pK a 11.12.

Figure 2 .
Figure 2. Plot of log K 1 k An for the reaction of 1 with anilines versus the pK a values of the corresponding anilinium ions.(The slope is 0.55.Points a, b, c, d, e and f represent 2,6-Et, 2,6-Me, 2,4-Me, 2-F, 2-Cl, 2-CN-anilines respectively).Values of K 1 k An decrease much more dramatically going from 2c to 2f.This indicates that the k An process is far more favourable with 2, 4-dimethylaniline than with 2cyanoaniline.A possible explanation is that the proton-transfer equilibrium is not strongly thermodynamically favoured.Hence as the basicity of the aniline decreases the rate constant for the process is reduced as shown in Scheme 2.The values of K 1 k An is higher than the corresponding values of K 1 k DABCO .This is likely to result from a reduction in the value of k An in the reaction of 1 since the proton transfer process involved is less thermodynamically favourable than in the corresponding reaction involving 1,3,5-trinitrobnzene.
Scheme 2.It should be noted that since proton-transfer is rate-determining in all these reactions, it is not possible to obtain values for the rate constants k 1 and k -1 relating to formation of the zwitterionic intermediates.
a Solutions containing DABCO also contain DABCO hydrochloride, 0.01 mol dm −3 .Measurements were made at 380 nm.b Calculated from eq