Arenesulfonates, nucleophilic reactions

Other routes to sulfonated phosphanes are the nucleophilic substitution of phosphides [Eq. (1)], which was first published in 1995 (26), and the reaction of halogenated arenesulfonates with PH derivatives (27) [Eq. (2)]. 

Lee s group has published extensive results on aminolysis of sulfonates.278 281 Thus the reactions of anilines witii 2-cyano-2-propyl and 1-cyanocyclooctylarenesulfonates in acetonidile have been stiidied.278 A dissociative, S k2 mechanism with a loose TS is supported from die usual LFERs. An 5k2 mechanism is also found for the reaction in acetone of (Z)-benzyl (X)-benzenesulfonates witii (Y)-pyridines.279 Nucleophilic substiditions witii die cycloalkyhnetiiylsulfonates (306) and anilines in MeOH were also sfridied.280 Finally die reaction of tiiiopheneethyl arenesulfonates (307) with anilines and AvA -dimethylanilines in MeCN has been reported on.281 Frontside-atiack in an 5n2 mechanism witii a four-centre TS is supported. 

Deprotonation of sulfonates by strongly basic nucleophiles can be avoided by using arenesulfonates instead of alkanesulfonates. Arenesulfonates can, however, give rise to another type of side reaction aromatic nucleophilic substitution. Nitro-arenesulfonates are particularly prone to attack by a nucleophile at the arene [89, 90] (Scheme 4.19). 

Figure 2.6 shows several methylations, which in each case take place as one-step SN reactions. The nucleophile is in each case a sulfonyl anion a methyl (arenesulfonate) reacts as electrophile. These classic experiments were carried out to clarify whether these methylations take place inter- or intramolecularly. 

The generation of an alkene by the reaction of a v/c-disulfonate ester with iodide (the Tipson-Cohen reaction) has been known since 1943 and in some cases it has proved useful where other methods have failed, as in the preparation of the spirocyclic triene (54 Scheme 22). The mechanism probably involves an initial nucleophilic displacement to give an iodohydrin sulfonate, which then undergoes iodide-induced elimination to the alkene. Methanesulfonates can be used as well as arenesulfonates. 

Ando and coworkers conducted isotope effect studies (entry 11) on the direct displacement reaction of benzyl arenesulfonates with dimethylaniline (DMA)38. They found that an electron-withdrawing substituent in the substrate (Y = 3-Br) caused the TS to shift to a later position along the reaction coordinate, which is consistent with that predicted by the Thornton rule (or anti-Hammond effect). The anilinolysis of phenylethyl arenesulfonates (entries 12 and 13) proceeds also by an SN2 mechanism. The reaction was found to proceed by a dissociative SN2 mechanism with a relatively small degree of aryl participation. The fraction of the phenonium ion intermediate captured by the aniline nucleophile in the aryl-assisted pathway has been shown to increase with a stronger nucleophile, and a four-center TS in an intermolecular SNi mechanism is suggested for the aryl-assisted pathway39,40. Under the same reaction conditions, benzylamine nucleophiles react at a rate ca two times faster than that of anilines. 

The nucleophilic substitution reactions of anilines with ero-2-norbomyl arenesulfonates, 2, present an interesting example of the preassociation mechanism55 (Scheme 1). The rate is faster with 2-exo (k2 = 15.9 x 10 4 and 3.24 x 10-5 M 1 s 1 when X = Z = H in MeOH and MeCN at 60.0 °C, respectively) than with 2-endo (k2 = 0.552 x 10 5 M 1 s 1 with X = Z = H in MeOH at 60.0 °C). These reactions are characterized by a large pz (1.8 and 1.2 for 2-exo and 2-endo) coupled with a small magnitude of px (—0.21 and —0.15 for 2-exo and 2-endo). The pz values for the aniline reactions are even larger than those for the SY 1 solvolysis in MeOH (pz =1.5 and 1.0 for solvolysis of 2-exo and 2-endo). Thus the abnormal substituent effect in the anilinolysis of 2 can only be accounted for by the preassociation mechanism of Scheme 1. The upper route is the normal S/v 1 pathway, and the lower route is the preassociation pathway. The preassociation step, Xass, and association of the Nu to the ion pairs, kn. occur in a diffusion limited or fast process and k is the rate-limiting step. This mechanism leads to second-order kinetics and therefore is an SY/2 process, but structural effects on rates are very similar to those of S l reactions, since the R+ Z pair consists essentially of the two free ions. 

Nucleophilic substitution reactions of l-(trimethylsilyl)ethyl arenesulfonates, 3, with anilines in MeCN at 65.0 °C was found to proceed by an Sw2 mechanism56. The pxz... 

Nucleophilic substitution reactions of aniline are also studied at tertiary alkyl carbon centers in MeCN66. The reactions with 2-cyano-2-propyl, 5, and 1-cyanooctyl, 6, arenesulfonates are reported in MeCN at 50.0 °C. 

Conversion of alcohols to sulfonate esters is a way of labilising them to nucleophilic substitution and elimination. The common leaving groups are arenesulfonates, particularly p-toluenesulfonate (tosylate), methanesulfonates (mesylate) and trifluromethanesulfonate (triflate) they are introduced by reaction of the acid chlorides (or, in the case of the trifluoromethanesulfonates, acid anhydrides) in a basic solvent such as pyridine. Traditionally, the reactions are carried out in pyridine as solvent, but both this solvent and the liberated... 

Accurate determination of the a for 1-AdCl requires solution of the full SCE equation. Unfortunately, this solution is difficult to accomplish because determining rates in weakly nucleophilic, nonhydroxylic solvents is a complex matter. An example is the study of Kevill and Kim (15) on the solvolysis of 1-adamantyl arenesulfonates in acetonitrile. These workers found that the reaction proceeded to give an early equilibrium between the reactant and the nitrilium ion formed by acetonitrile acting as nucleophile. So that the equilibrium could be removed and good kinetics obtained, trapping of the cation with azide ion to give a tetrazole product was necessary. Presumably, other solvolyses of 1-Ad derivatives in other weakly nucleophilic solvents would be similarly complex. Having rates in these nonhydroxylic solvents is critical if the complete equation is to be solved because of colinearity between certain of the independent variables in hydroxylic solvents. 

Water is not an especially nucleophilic solvent, but water effectively solvates anionic leaving groups so that in water considerable ionization in the transition state should occur (72). The surfaces of micelles are water-rich (34, 35) and values of k+/k for hydrolyses of alkyl halides and arenesulfonates suggest that nucleophilic participation is dominant in reactions at methyl... 

Quite early. Ingold and coworkers (Baker et al., 1928) proposed carbocations as intermediates in these reactions, as the product pattern and the stereochemistry display similarities to those of nucleophilic aliphatic substitutions of molecules with anionic leaving groups like halogenide ions, arenesulfonate ions, etc. (7-2). 

Isomerization may accompany nucleophilic substitution during the solvolysis of carboxylate and arenesulfonate esters of unsaturated alcohols. Most of the substrates for which such isomerization reactions have been observed are esters of allylic alcohols. If such an ester is optically active by virtue of having an asymmetric a-carbon atom, three experimentally observable processes occur simultaneously racemization, solvolysis, and allylic isomerization. All three of these processes involve formation of planar, achiral allylic carbonium ions as intermediates, viz-... 

Nucleophilic substitution reactions that occur under conditions of amine deamination often differ significantly in stereochemistry, compared with that seen in halide or arenesulfonate solvolysis. The results of four key substrates are summarized in Table 5.13. It can be seen (entry 1) that displacement of nitrogen on the 1-butyldiazonium ion is much less stereospecific than the 100% inversion observed on acetolysis of the corresponding brosylate. Similarly, the secondary system (entry 2) affords 2-butyl acetate with only 28% inversion of configuration. Furthermore, a crossover to net retention of configuration is observed as the alkyl group becomes better able to stabilize a carbonium ion. The small net retention (10%) observed in deamination of 1-phenylethylamine increases to 28% retention in the tertiary benzylic system 2-phenyl-2-butylamine. 

Nucleophilic substitution reactions that occur under conditions of amine diazotization often differ significantly in stereochemistry, as compared with that seen in halide or arenesulfonate solvolysis. Diazotization occurs via an N-nitroso amine which decomposes to a carbonium ion, molecular nitrogen, and water ... 

Reaction with Thiocarboxylic Acids, Phosphoric Acids, Sulfonic Acids, and their Derivatives. Thiocarboxylic acids, - dithiocarboxylic acids, and dimethyldithiocarbamic acid zinc salt, as well as various phosphorus oxyacids and phosphorus thioacids, can also be utilized. a,o)-Mercapto alcohols form cyclic thioethers whereas thiols react with both DEAD and TPP-DEAD to form disulfides. 2-Mercaptoazoles also react with alcohols in the presence of DEAD and TPP. Although arenesulfonic acids do not enter into the reaction, a combination of DEAD-TPP with methyl p-toluenesulfonate as a nucleophile carrier gives the corresponding alkyl sulfonates (eq 14). Altema-... 

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