Sodium -toluenesulfinate

Prepared by Frank C. Whitmore and Francis H. Hamilton Checked by J. B. Con ant and Paul Allen, Jr. 

The free sulfinic acid may be prepared by dissolving the sodium salt in cold water and carefully acidifying the solution with hydrochloric acid. An excess of the latter must be avoided, as it dissolves the acid to a certain extent. The sulfinic acid is difficult to dry without partial conversion into the sulfonic acid. 

Toluenesulfinic acid and its salts have been prepared by three general methods (1) The reduction of the sulfonyl chloride. The reagents which have been used for this are sodium amalgam,1 zinc dust in alcohol or water,2 sodium sulfite,3 sodium sulfide,4 potassium hydrosulfide 5 (the thio acid being first formed) and sodium arsenite.6 (2) From toluene by the Friedel and Crafts reaction, using either sulfur dioxide and hydrogen chloride 7 or sulfuryl chloride.8 (3) From -toluidine by diazotization and 

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Sodium -tolueuesulfinate dihydrate can be used equally well. The checkers used anhydrous sodium -toluenesulfinate from Aldrich Chemical Company, Inc. This material was determined by titration to be 87% pure and gave lower yields. The yield stated was obtained by using stoichiometric amounts based on calculated purity. Sodium p-toluenesulfinate from other suppliers was found less pure and gave considerably lower yields. 

The submitters used anhydrous sodium -toluenesulfinate ( purum quality, ca. 97% from Fluka A G), and the checkers purchased the reagent from Aldrich Chemical Company, Inc. 

A recently discovered novel synthesis of toluenebenzylsulfoxides is based on the reaction of AT-phenylacetylbenzotriazoles with sodium toluenesulfinates [27a]... 

Sodium >-toluenesulfinate dihydrate, 34, 93 Sommelet reaction, 33, 93 Sorbic acid, 5-hydroxy-0-methyl, 5-lactone, 32, 57 Stannic chloride, 33, 91 Stearic acid, 34, 15 Stearolic acid, 37, 77 Stearone, 33, 84 cis-Stilbene, 33, 88 Irans-Stilbene, 33, 89... 

Aminopyrazole may also be obtained by hydrolysis of 3-imino-l-(/>-tolylsulfonyl)pyrazolidine with aqueous alkali. In this case the pyrazolidine (239 g., 1.00 mole) is added to a solution of 40 g. (1.0 mole) of sodium hydroxide in 250 ml. of water at 75°, the resulting solution is stirred briefly, and the water is removed at reduced pressure. 3(5)-Aminopyrazole is separated from the sodium />-toluenesulfinate by several extractions with isopropyl alcohol. 

In the presence of catalytic amounts of both sodium -toluenesulfinate and potassium cyanide, the reaction of benzaldehyde with 4-chloroquinazoline 89 gave 4-benzoylquinazoline 90 in good yield <1998H(47)407>. The reaction involves activation of the benzaldehyde by cyanide addition, and activation of the quinazoline as the 4-toluenesulfonyl derivative. 

A. Ethyl l l- p-tolylsulfonylmethyl)carbamate,[Garbamic acid, methyl-phenylsulfonylmethyl)-, ethyl ester], A solution of 178 g. (1.0 mole) of sodium -toluenesulfinate (Note 1) in 11. of water is placed in a 3-1., three-necked flask, equipped with a condenser, an efficient mechanical stirrer, and a thermometer. After addition of 100 ml. (108 g.) of a 34-37% solution of formaldehyde (ca. 1.2-1.4 moles) (Note 2), 107 g. (1.2 moles) of ethyl carbamate (Note 3), and 250 ml. of formic acid (Note 4), the stirred solution is heated to 70°. Soon after this temperature is reached, the reaction mixtiu e becomes turbid by separation of the... 

To 179 g. (108 ml., 1.5 moles) of thionyl chloride (Note 1) contained in a 250-ml. round-bottomed flask, 42.8 g. (0.2 mole) of powdered sodium >-toluenesulfinate dihydrate 2 (Note 1) is added in portions at room temperature over a 10- to 15-minute period. A vigorous reaction occurs with the evolution of hydrogen chloride and sulfur dioxide. As the first portions of the sulfinate are added, the temperature of the reaction mixture rises, but it soon drops to approximately 0° as the additidn proceeds (Note 2). 

Redistilled thionyl chloride is recommended. No difficulties were encountered when the color of the reagent was deep yellow. The sodium -toluenesulfinate dihydrate should be thoroughly air-dried to remove mechanically bound water. 

The cyclopentene annulations can also occur in the reactions of alkynyliodo-nium salts with nitrogen- and sulfur nucleophiles (Scheme 61). Specifically, azi-docyclopentene 155 is formed upon treatment of octynyliodonium tosylate 154 with sodium azide in dichloromethane [123]. The reaction of alkynyliodonium salt 156 with sodium toluenesulfinate results in the formation of substituted indene 157 via alkylidene carbene aromatic C-H bond insertion [124]. 

A variety of substituted 2-cyclopentenones are obtained in good yields by the reaction of sodium toluenesulfinate with /Tketoethynyl(phenyl)iodonium tri-flates [125]. Several specific examples of this reaction are shown in Scheme 62. This methodology readily affords not only simple cyclopentenones but also fused bicyclic systems 161 and y-lactams 163. 

Another method for deallylation is the Pd-catalyzed transfer of the allyl group to reactive nucleophiles. Sodium 2-ethylhexanoate [141], morpholine [142], dimedone [143] and AA-dimethylbarbituric acid [144] are used as allyl scavengers. It is claimed that benzenesulfinic acid 331 or sodium toluenesulfinate are the best allyl scavengers [145]. 

If the sodium />-toluenesulfinate is not finely powdered, reaction occurs more slowly with emission of slight crackling sounds. 

The reactions of / -ketoethynyl- and ) -amidoethynyl(phenyl)iodonium triflates, 17 and 18, with sodium / -toluenesulfinate illustrate the synthetic potential of alkynyliodonium salts33. Although the direct attachment of a carbonyl group to the / -carbon atom of the triple bond in alkynyliodonium ions might be expected to facilitate alkynyl sulfone formation via the Ad-E mechanism, this mode of reactivity has not been observed. Instead, the MC pathway with carbenic insertion dominates and affords sulfones containing the... 

TABLE 5. Cyclopentenyl sulfones and sulfonyl lactams from (ketoethynyl)iodonium and (amido ethynyl)iodonium triflates 17 and 18 with sodium / -toluenesulfinate in dichloromethane"... 

The propensity of the thiocyanate ion for alkynylation with alkynyliodonium ions has also been demonstrated with a series of bis(phenyliodonium)diyne triflates (equations 61 and 62)43. The efficient production of diynediyl dithiocyanates in these reactions may be contrasted with the favored formation of mono- and bis-cyclopentenyl sulfones from bisiodonium diyne salts and sodium/ -toluenesulfinate (see equation 57)86. 

The butynyl(phenyl)iodonium triflates 243, possessing an ether or acetal linkage at C-4, react with sodium />-toluenesulfinate to give the 3-tosyldihydrofurans 244 (00OL2603, OOJOC8659). These formal carbenic C-O bond insertions are thought to occur through vinyloxonium ylide intermediates (Scheme 67). 

The carbene-insertion pathway has recently been applied in total asymmetric syntheses of the anti-leukemic alkaloid, (—)-agelastatin A, and the dibromo analog, (-)-agelastatin B (02JA9060, 02JOC7096). Treatment of the (oxazolidinonyl)propynyliodonium triflate 250 with sodium />-toluenesulfinate leads to a mixture of the bicyclic oxazolidinone 251 and the carbenic rearrangement product 252 (Scheme 70) compound 251 is a key intermediate in the agelastatin synthesis. 

Alkynyltriphenylbismuthonium salts react with sodium />-toluenesulfinate in dual reaction modes depending on the solvents employed (Equation (133)).217 When the reaction is conducted in DMF, 1-tosylcyclopentene is formed through 1,5-C-H insertion of an alkylidene carbene intermediate, generated via Michael addition of the sulfinate anion to the /3-carbon. When the reaction is carried out in MeOH, l,2-bis(sulfonyl)alkenes are produced via sequential Michael addition and nucleophilic substitution of the sulfinate anion. 

The solid sodium -toluenesulfinate which separates is collected by filtration and mixed with 400 g. (4.76 moles) of sodium bicarbonate and 490 g. (370 ml., 3.88 moles) of dimethyl sulfate (Note 4) in a 3-1. three-necked round-bottomed flask equipped with a mechanical stirrer, a reflux condenser, and a 1-1. separatory funnel containing 925 ml. of water. Water (75-100 ml.) is added from the separatory funnel to make the mixture fluid enough for stirring. The remainder of the water is then added... 

Methyl -tolyl sulfone has been prepared by oxidation of methyl -tolyl sulfide with hydrogen peroxide or ruthenium tetroxide, by alkylation of sodium -toluenesulfinate with methyl iodide or with methyl potassium sulfate, by decarboxylation of -tolylsulfonylacetic acid, by thermal decomposition of tetramethylammonium -toluenesulfinate, " by reaction of cw-bis-(j >-tolylsulfonyl)-ethene with sodium hydroxide (low yield), by the reaction of methanesulfonyl chloride with toluene in the presence of aluminum chloride (mixture of isomers)by... 

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