Para-Toluenesulfonic acid

You will note that the oxygen atoms attached to carbons 5 and 12 in 43 reside in proximity to the C-9 ketone carbonyl. Under sufficiently acidic conditions, it is conceivable that removal of the triethylsilyl protecting groups would be attended by a thermodynamically controlled spiroketalization reaction.30 Indeed, after hydro-genolysis of the C-26 benzyl ether in 43, subjection of the organic residue to the action of para-toluenesulfonic acid in a mixture of methylene chloride, ether, and water accomplishes the desired processes outlined above and provides monensin methyl ester. Finally, saponification of the methyl ester with aqueous sodium hydroxide in methanol furnishes the sodium salt of (+)-monensin [(+)-1], Still s elegant synthesis of monensin is now complete.13... 

Ketal 73 can be formed in a yield of about 60 % by refluxing a solution of tetronic acid (36), ethylene glycol, and a catalytic amount of para-toluenesulfonic acid in benzene for approximately 12 hours. With only one electrophilic site, 73 reacts smoothly with Dibal-H to give lactol 35 in 84% yield. Compound 35, a participant in a ring-chain tautomeric equilibrium process,18 should be regarded as a latent aldehyde. This substance can, in fact, serve as... 

The completion of the total synthesis only requires a few deprotection steps. It was gratifying to find that the final deprotections could be conducted smoothly and without compromising the newly introduced and potentially labile trisulfide residue. In particular, exposure of intermediate 101 to the action of HF pyridine results in the cleavage of all five triethylsilyl ethers, providing 102 in 90% yield (Scheme 23). Finally, hydrolytic cleavage of the ethylene ketal with aqueous para-toluenesulfonic acid in THF, followed by removal of the FMOC protecting group with diethylamine furnishes calicheamicin y (1) (see Scheme 24). Synthetic calicheami-cin y, produced in this manner, exhibited physical and spectroscopic properties identical to those of an authentic sample. 

The asymmetric synthesis of 2,3-diamino acids can be accomplished by the addition of chiral enolates to prochiral imines. For example, reaction of morpholine-2-one 103, derived from (S)-phenylglycinol, with N-benzyl ben-zaldimine in the presence of pyridine and para-toluenesulfonic acid at high... 

Several procedures were developed for the transformation (223—>-224). The most commonly used procedures are based on treatment of the nitroso acetal with benzene saturated with HC1 (204, 205) and by the addition of a catalytic amount of para -toluenesulfonic acid or trifluoroacetic acid (206). The introduction of branched radicals at the silicon atom decelerates elimination of silanol. 

Isosorbide Dinitrate Isosorbiddinitrate, 1,4 3,6-dianhydrosorbate-2,5-dinitrate (19.1.4), is synthesized by intermolecular dehydration of D-sorbite into isosorbide (19.1.3) using para-toluenesulfonic acid and subsequent nitration of the two hydroxyl groups by nitric acid [5-7]. 

In 2001, Albrecht Berkessel and Nadine Vogl reported on the Baeyer-Villiger oxidation with hydrogen peroxide in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as solvent in the presence of Brpnsted acid catalysts such as para-toluenesulfonic acid (equation 85) . Under these conditions cyclohexanone could be selectively transformed into the corresponding lactone within 40 min at 60 °C with a yield of 92%. Mechanistic investigations of Berkessel and coworkers revealed that this reaction in HFIP proceeds by a new mechanism, via spiro-bisperoxide 234 as intermediate, which then rearranges to form the lactone. The study illustrates the importance of HFIP as solvent for the reaction, which presumably allows the cationic rearrangement of the tetroxane intermediates. 

As lactams of 4-amino-3-oxobutanoic acids, tetramic acids react with amines (87JPJ858) and with phenylhydrazine. The latter reaction is catalyzed with para-toluenesulfonic acid. Thus, for example, l/2b give phenyl-hydrazone 65 in 80% yield that, in turn, under the conditions of the Fischer indole synthesis, may give rise to pyrrolo[4,3-b]indolene 66 (90TH1). (See Fig. 31.)... 

Aflask was charged with methyl pyruvate (8.25 mol), trimethyl orthoformate (10 mol), methanol (1060 g), and para-toluenesulfonic acid monohydrate (0.041 mol) and then stirred at 58°C for 10 hours. It was then treated with 28% methanol solution of sodium methoxide (8 g) and concentrated. After distillation the product was isolated as a colorless transparent liquid in 98% purity having a boiling point (bp) of 80°C 40mmHg. 

Dehydration of alcohol to alkenes usually does not require superacidic conditions. Surprisingly, however, perfluroalkylcyclopentanols could not be dehydrated with para-toluenesulfonic acid, but alkenes could be isolated with the use of the stronger acid Nafion-H albeit in low yields737 [Eq. (5.282)]. 

Androsta-l,4,6-triene-3,17-dione 246, when treated with ordinary acid catalysts such as acetic anhydride-para-toluenesulfonic acid, gives the meta phenolic product 247 (Scheme 5.88). However, under HF SbF5 catalysis at 50°C the phenolic product 248 is obtained in 75% yield855 (Scheme 5.88). The mechanism of the above discussed phenol-dienone and dienone-phenol rearrangement has been investigated in detail.856 857... 

To avoid stannyl reagents, there is the possibility to synthesize the same building block in one more step. First step is the formation of the benzylidene acetal 38 at the positions C-4 and C-6 of the glucal 10. The acetal formation at C-4 / C-6 is favored because you can get a six-membered instead of a five-membered ring at the position C-3 / C-4. To form 38 benzaldehyde dimethyl acetal 39 can be used with catalytic amounts of para-toluenesulfonic acid. 

In a 30-liter reactor, reflux 12.5 kg of (2S,3aS,7aS)-2-carboxyperhydroindole, 50 kg of para-toluenesulfonic acid and 14.2 kg of benzyl alcohol and 38.4 kg of toluene, removing the water formed with the aid of a continuous separator. When no more water separates out, cool, filter off the precipitate of para-toluenesulfonate of the benzyl ester of (2S,3aS,7aS)-2-carboxyoctahydroindole formed, and dry. Yield 91.3%. 

In addition to forming esters with carboxylic acids, alcohols form inorganic esters with inorganic acids such as nitric acid, sulfuric acid, and phosphoric acid. In each type of ester, the alkoxy (—OR) group of the alcohol replaces a hydroxyl group of the acid, with loss of water. We have already studied tosylate esters, composed of para-toluenesulfonic acid and alcohols (but made using tosyl chloride, Section 11-5). Tosylate esters are analogous to sulfate esters (Section 11-13A), which are composed of sulfuric acid and alcohols. 

An ester of an alcohol with para-toluenesulfonic acid. Like halide ions, the tosylate anion is an excellent leaving group, (p. 477)... 

The product from Step 1 (6.21 g), 3 ml 2-mercaptoethanol and para-toluenesulfonic acid (0.2 g) were dissolved in 150 ml toluene and the mixture heated under Dean-Stark conditions 3 hours. The mixture was cooled, washed with 50 ml NaHCOj solution and 2.5 ml water, dried, and concentrated. The mixture was purified using chromatography on silica gel with hexane/EtOAc, 9 1, and the product isolated in 90% yield. H-NMR data supplied. 

Two variants of this rearrangement have been reported. One uses triethyl phosphite instead of diethyl chlorophosphite. Thus, in the presence of a catalytic amount of para-toluenesulfonic acid, triethyl phosphite reacts with propargyl alcohol in DMF at room temperature to give a mixture of diethyl allenylphosphonate (51%) and diethyl 1-propynylphosphonate (14%). The second variant is based on the conversion of dialkyl allenylphosphonates (R , R H, R = H, Scheme 1.19) into dialkyl 1-alkynylphosphonates by a photochemically allowed [l,3s]-sigmatropic shift in ( ,11, with 46-50% yields. ... 

Some cyclic enamides or enecarbamates can be easily and directly prepared by the condensation of primary amides or carbamates with cyclic ketones in the presence of para toluenesulfonic acid as catalyst and by using a Dean Stark apparatus to remove water (Scheme 9.3) [9]. 

Alcohol esterification is usually catalysed by homogeneous catalysts such as sulfuric acid (5), para-toluenesulfonic acid (6) or bases such as sodium (potassium,. ..) hydroxide (carbonate,...) (3,7). Unfortunately, it is well known that these bases favour the production of soaps. Moreover, homogeneous catalysts are corrosive, difficult to separate from the products and lead to excessive wastes (salts). 

The mechanism of the acid-catalysed (AH = acid catalyst) polyesterification reaction (for example using para toluenesulfonic acid as the catalyst) is presented in the following equilibrium reactions (8.11-8.14). The mechanism is very similar to those of the self catalysed polyesterifications. 

SCHEME 7.1 The synthetic sequence to reach ebalzotan in 13 linear steps incorporating a de novo assembly of the chroman nucleus and a diastereomer resolution (abbreviations DMF = Ai,Ai-dimethylformamide p-TSA = para-toluenesulfonic acid). 

To overcome tbe problem of tbe bigb amount of graphite utilized and mainly to avoid tbe use of tbe expensive and pollutant acyl balides and benzene, graphite can be coupled with para-toluenesulfonic acid and utilized to activate the more ecocompatible carboxylic acids toward electrophilic acylation. i With this catalyst, not only a solvent-free process can be developed but also high yields with not activated aromatic substrates and with unactivated carboxylic acids (i.e., para-nitrobenzoic acid) can be obtained (Table 4.25). 

Interestingly, in the presence of graphite or para-toluenesulfonic acid alone, no acylated products are isolated. The effect of the solvent is detrimental since only traces of the products are detected when the reactions are carried out in methylene chloride or chloroform. It must be underlined that graphite can be reused after simple washing with ethyl acetate and water, but the para-toluenesulfonic acid, which is not adsorbed on the graphite during the reaction, must be added again for the successive runs. 

Table 4.25 Aromatic acylation with carboxylic acids in the presence of graphite-para-toluenesulfonic acid mixture...

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