Nucleophiles sulfonation, toluene

Because halides are poorer leaving groups than p toluene sulfonate alkyl p toluene sulfonates can be converted to alkyl halides by 8 2 reactions involving chloride bro mide or iodide as the nucleophile... 

Condensation of 2-aminothiophenol with the /3-chlorocinnamaldehyde in the presence ofp-toluene sulfonic acid (PISA) gave good yield of benzothia-zole (Scheme 14). The mechanism suggested in this work is beUeved to proceed via a nucleophilic attack of the sulfur atom in an addition-ehmination sequence followed by a spontaneous cyclization and ejection of acetaldehyde [15]. These investigations were performed in a domestic microwave reactor and need 1.5 min for completion (65% yield). Here again, oil bath heating seems to be inferior, providing a maximum conversion of 53% after... 

If the rearrangement of oxime sulfonates is induced by organoaluminum reagents,the intermediate (71) is captured by the nucleophile originally attached to the Al. By this means an oxime can be converted to an imine, an imino thioether (R—N—C—SR), or an imino nitrile (R—N—C—In the last case, the nucleophile comes from added trimethyl si lyl cyanide. The imine-producing reaction can also be accomplished with a Grignard reagent in benzene or toluene. ... 

Acetals and ketals are very important protecting groups in solution-phase synthesis, but only a few constructs have been used as linkers in solid-phase synthesis (Tab. 3.3). The THP-linker (22) (tetrahydropyran) was introduced by Ellman [54] in order to provide a linker allowing the protection of alcohols, phenols and nitrogen functionalities in the presence of pyridinium toluene sulfonate, and the resulting structures are stable towards strong bases and nucleophiles. Other acetal-linkers have also been used for the attachment of alcohols [55, 56]. Formation of diastereomers caused by the chirality of these linkers is certainly a drawback. Other ketal tinkers tike... 

Methylation of 3-hydroxy-5-phenyl-l,2,4-thiadiazole (23) with dimethyl sulfate and sodium hydroxide at room temperature gives a mixture of (24) and (133). When methylation is carried out using methyl toluene-4-sulfonate at 100°C, no (9-methylation is observed and compound (24) and the meso-ionic derivative (25) are produced, (Scheme 7) <84JCS(Pi)75>. Reaction of (23) with dimethyl acetylenedicarboxylate yields the fumarate (134) and the maleate (135) derivatives which are formed by nucleophilic addition <84JCS(Pi)75>. 

The vinyl substituent at C-2 can also act as a Michael acceptor and reaction with certain nucleophiles gives rise to 1,4-addition compounds. For example, p-toluene-sulfonic acid catalyzed addition of thiols to 2-vinyl- or 2-isopropenyl-5(47/)-oxazolones 136 gave, almost exclusively, the Michael adducts 137 that were used... 

Okamoto and co-workers noted that N-phenylhydroxylamine gave predominately diphenylamine on treatment with benzene in TFA but mostly 4-aminobiphenyl and 2-aminobiphenyl in the stronger acid trifluoromethane-sulfonic acid (TFSA). Similar results were obtained if benzene was replaced by toluene or anisole. The authors suggested that the reaction in TFA proceeded through O-protonated hydroxylamine either via a direct Sn2 displacement on N by the aromatic nucleophile or via attack of the aromatic compound on the N of a nitrenium ion. In TFSA they favored a mechanism in which the diprotonated hydroxylamine lost water to generate an iminium-benzenium dication (11, Scheme 5), a protonated nitrenium ion. " This... 

The three l,4 3,6-dianhydrohexitols show the shielding effect of the cts-fused oxolane ring on their di-O-sulfonyl derivatives. As C-2 and C-5 of 1,4 3,6-dianhydro-D-mannitol 2,5-di-p-toluene-sulfonate and 2,5-dimethanesulfonate are open to attack from the exo direction, they react readily with such nucleophilic reagents as benzoate in /V,iV-dimethylfoimainide,94 acetate in acetone,93 thioacetate,95 phthalimide in A/,JV-dimethylformamide,93 and iodide in acetic anhy-dride.59<6) Inversion occurs at these positions and the L-iditol configuration results, as pointed out in the several examples in Table V. However, hydroxide ion may merely saponify,92 with retention of configuration.93... 

Benzylic halides and sulfonates show a wide range of reactivity towards nucleophiles. Activation and deactivation by o-/p-donors (e.g. OR) and acceptors (e.g. N02), respectively, are consistent with PAR. In each case the benzylic carbon atom is identified as acceptor or donor. The trends are also reflected in the relative acidities of the corresponding toluene derivatives. 

Since the pioneering work of Karl Freudenberg on displacements of carbohydrate p-toluene-sulfonates [1-5], bimolecular nucleophilic substitutions became one of the most employed and useful reactions in carbohydrate chemistry. Indeed SN2-type reactions have allowed the introduction of a variety of heteroatoms (halogens, N-, O-, S-) into carbohydrates, and the resulting compounds have been used in many synthetic and biological contexts [6],... 

As in part (a), identify the nucleophilic anion in each part. The nucleophile replaces the p-toluene-sulfonate (tosylate) leaving group by an SN2 process. The tosylate group is abbreviated as OTs. 

If, however, we first make the pom-toluene sulfonate ( tosylate ) by nucleophilic attack of the OH group on the sulfonyl chloride TsCl in pyridine solution, the sulfonate will be formed with retention as no bonds have been formed or broken at the chiral carbon atom. This is a substitution reaction too, but at sulfur rather than at carbon. 

In a similar manner, toluene-p-sulfonate derivative of alcohols on nucleophilic displacement with trimethylamine N-oxide followed by treatment with a base gives the carbonyl compound and trimethylamine. 

Hydrogenolysis of the toluene-4-sulfonate of an alcohol may be carried out with a nucleophilic hydride such as lithium aluminium hydride. There are also a series of radical methods based on the reduction of alkyl halides with tri- -butyltin hydride (BUjSnH). Finally, the source of the hydrogen may be the electrophilic proton, exemplified by the decomposition of organometallic reagents such as the Grignard reagent with water. 

Many of the convenient methods of preparing alkyl halides are based on the reactions of alcohols with reagents such as thionyl chloride and phosphorus pentachloride. These are dealt with in more detail in Section 2.3 on alcohols. The nucleophilic substitution of an alkyl methanesul-fonate or toluene-4-sulfonate with a sodium or potassium halide is a useful method. 

Alkoxides are nucleophiles and may be used to react with alkyl hahdes or alkyl toluene-4-sulfonates to form ethers (Scheme 2.1 Ic). 

The sulfonyl halides (ArSOjCl) convert the alcohol into a sulfonate (ArSOjOR), which is a better leaving group than the hydroxyl group. This allows a range of nucleophilic substitutions to be carried out, many of which parallel those found with alkyl halides. Alkyl halides such as iodides are formed by the nucleophilic substitution of the sulfonate by an iodide ion. The reaction in this case proceeds with inversion of configuration. Treatment of the sulfonate esters with bases such as sodium methoxide or collidine (2,4,6-trimethylpyridine), or even just heating them, can lead to the elimination of toluene-4-sulfonic acid and the formation of an alkene. 

The synthesis of this type of compound was achieved by nucleophilic attack of the nitrogen of the C-3 hydrazone residue on C-6 of 65c when it carries a leaving substituent such as a sulfonyloxy group or a bromine atom. This intramolecular heterocyclization process was achieved by the action of sodium iodide in acetone or by the action of acetic anhydride on the mono-O-p-toluene sulfonate to give 111 and 114, respectively (82MI5) (Scheme 28). The spectral data confirmed the assigned structure. 

---