Para-toluenesulfonate esters

A space-filling model of a para-toluenesulfonate ester. B... 

Compound 4.2 can undergo an elimination by treating with sulfuric acid or by converting it into a para-toluenesulfonate ester. Structure 4.3, followed by treatment with base. Which route would enable us to maximize the yield of elimination product ... 

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... 

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%. 

Add approximately 3.5 kg of triethylamine to a suspension of approximately 5 kg of para-toluenesulfonate of the benzyl ester of (2S,3aS,7aS)-2-carboxyoctahydroindole in approximately 60 kg of ethyl acetate, followed by approximately 6 kg of 1-hydroxybenzotriazole, approximately 7.5 kg of the N-[(S)-l-carbethoxybutyl]-(S)-alanine and approximately 7.0 kg of dicyclohexylcarbodiimide. Stir, cooling slightly for approximately 3 hours, then filter off the dicyclohexylurea formed and wash the organic phase with water. The dried organic phase is evaporated to dryness and benzyl ester of (2S,3aS,7aS)-l- 2-[l-(ethoxycarbonyl)-(S)-butylamino]-(S)-propionyl octahydroindole-2-carboxylic acid was obtained. Yield 92.3%. 

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 1,3 dipole diazomethane is a mild reagent to furnish methyl esters (see Chapter 13), but it has some disadvantages, too it is volatile, toxic and furthermore explosive. For this reason it has to be prepared by reaction of KOH with A-methyl-A-nitroso-para-toluenesulfon-amide (carcinogenic ) or in situ Another simple method to protect the COOH functionality of the neuraminic acid is the esterification with methanol as solvent and reactand under H " catalysis e. g. ion exchanger. 

Once the alcohol has been activated by being converted into a sulfonate ester, the appropriate nucleophile is added, generally under conditions that favor Sn2 reactions. The reactions take place readily at room temperature because the leaving group is so good. For example, a para-toluenesulfonate ion is about 100 times better than a chloride ion as a leaving group. Sulfonate esters react with a wide variety of nucleophiles, so they can be used to synthesize a wide variety of compounds. 

Swem oxidation A mild oxidation, using DMSO and oxalyl chloride, that can oxidize primary alcohols to aldehydes and secondary alcohols to ketones, (p. 465) tosylate ester An ester of an alcohol with para-toluenesulfonic acid. Like halide ions, the tosylate anion is an excellent leaving group, (p. 469)... 

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