Tosylation p-toluenesulfonyl chloride

In the reaction with enamino ketones derived from dimedone (e.g., 49) p-toluenesulfonyl chloride gives the chloroiminium cation (138) isolated as the perchlorate. This indicates that initial O sulfonation is followed by addition of chloride ion and subsequent expulsion of tosylate (42) in a manner similar to the trichloroacetyl chloride reaction with 49 (Section IV.A). 

Esterification of 136 with p-toluenesulfonyl chloride leads to the tosylate (139). Displacement of the ester with guanidine affords guanoxane (140). This drug, not surprisingly, shows peripheral sympathetic blocking activity and is therefore used in control of hypertension. 

Deoxy-D-jcylo hexose 6-(dihydrogen phosphate) (21) has also been synthesized (2) the reaction sequence makes use of 3-deoxy l 2,5 6-di-O-isopropylidene D-galactofuranose (16), a compound that can be easily prepared from D-glucose (2, 60). The mono-isopropylidene derivative (17) formed by partial hydrolysis of the di-ketal is converted into the 6-tosylate (18) by reaction with one molar equivalent of p-toluenesulfonyl chloride. From this the epoxide (19) is formed by reaction with sodium methoxide. Treatment of the anhydro sugar with an aqueous solution of disodium hydrogen phosphate (26) leads to the 6-phosphate (20)... 

Alcohols react with p-toluenesulfonyl chloride (tosyJ chloride, p-TosCl) in pyridine solution to yield alkyl tosylates, ROTos (Section 11.1). Only the 0-H bond of the alcohol is broken in this reaction the C—O bond remains intact, so no change of configuration occurs if the oxygen is attached to a chirality center. The resultant alkyl tosylates behave much like alkyl halides, undergoing both SN1 and Sjsj2 substitution reactions. 

Sulfur compounds have also been widely studied as activating agents for polyesterification reactions. p-Toluenesulfonyl chloride (tosyl chloride) reacts with DMF in pyridine to form a Vilsmeir adduct which easily reacts with carboxylic acids at 100-120° C, giving highly reactive mixed carboxylic-sulfonic anhydrides.312 The reaction is efficient both for aromatic dicarboxylic acid-bisphenol312 and hydroxybenzoic acid314 polyesterifications (Scheme 2.31). The formation of phenyl tosylates as significant side products of this reaction has been reported.315... 

Enolizahon of cyanoketone rac-5 under the previously optimized conditions, followed by reaction with p-toluenesulfonic anhydride afforded a 90 10 ratio of the two expected enol tosylates in 90% yield. An immediate advantage of the tosylates compared to the triflate was seen on isolation, when the desired compound 32 was found to be a crystalline solid. In this way an 85% isolated yield of 32 as a single isomer could be achieved without the need for chromatography (Scheme 9.24). Use of p-toluenesulfonyl chloride in place of the anhydride led to a-chlorination... 

The variation in the antiscorbutic activity displayed by the various analogs of L-ascorbic acid makes it abundantly clear that the activity is dependent upon the stereochemical configuration of the molecule as a whole, and it would appear that the more closely the structure of a particular analog approaches that of the natural Vitamin C the greater will be the antiscorbutic power. Support for this view is illustrated by 6-desoxy-L-ascorbic acid which is obtained from L-sorbose.2 -80 Condensation of L-sorbose with acetone gives a mixture of 2,3-isopropylidene-L-sorbose (LII) and the diisopropylidene derivative. Treatment of LII with p-toluenesulfonyl chloride yields l,6-ditosyl-2,3-isopropylidene-L-sorbose (LIII). The greater reactivity of the tosyl group at C6 enables... 

The p-toluenesulfonyl chloride should be free of j-toluenesulfonic acid, otherwise potassium p-toluenesulfonate will be formed and will result in the formation of tosylates, rather than thiotosylates. The reagent used by the checkers was obtained from British Drug Houses Ltd. and was purified according to the following procedure.4 A benzene solution of the tosyl chloride was washed with 5% aqueous sodium hydroxide, dried with magnesium sulfate, and then distilled under reduced pressure, b.p. 146° (15 mm.). 

Dialkyl N-(benzoxazin-4-yl)methylenemalonates and their optically active forms (1728) were prepared in the reaction of the appropriate pheny-laminomethylenemalonate (1727), triphenylphosphine, and diethyl azodi-carboxylate in THF at -20°C (89EUP3228I5). The hydroxyl group of racemic and optically active phenylaminomethylenemalonates (1727) were tosylated with p-toluenesulfonyl chloride in pyridine, and the products were cyclized by heating in DMF at 80°C in the presence of potassium carbonate and a catalytic amount of 18-crown-6-ether to give 1728 (89EUP322815). 

Axenrod and co-workers reported a synthesis of TNAZ (18) starting from 3-amino-l,2-propanediol (28). Treatment of (28) with two equivalents of p-toluenesulfonyl chloride in the presence of pyridine yields the ditosylate (29), which on further protection as a TBS derivative, followed by treatment with lithium hydride in THF, induces ring closure to the azetidine (31) in excellent yield. Removal of the TBS protecting group from (31) with acetic acid at elevated temperature is followed by oxidation of the alcohol (32) to the ketone (33). Treatment of the ketone (33) with hydroxylamine hydrochloride in aqueous sodium acetate yields the oxime (34). The synthesis of TNAZ (18) is completed on treatment of the oxime (34) with pure nitric acid in methylene chloride, a reaction leading to oxidation-nitration of the oxime group to em-dinitro functionality and nitrolysis of the A-tosyl bond. This synthesis provides TNAZ in yields of 17-21 % over the seven steps. 

The 2-ethoxysulfonyl-p-toluenesulfonate (37.2.11) necessary for this reaction is in turn made by tosylation of 2-ethylsulfonyl ethanol using p-toluenesulfonyl chloride [51-53]. 

The tosylates may be prepared by treating the nitrosohydroxylamine with p-toluenesulfonyl chloride in aqueous sodium bicarbonate solution, in acetone-aqueous sodium hydroxide mixtures, or in benzene solution with the preformed salts of the nitrosohydroxylamines. 

A. 3-Methyl-3-(toluenesulfonyloxymethyl)oxetane [Oxetane tosylate, (1)7 A dry, 1-L, round-bottomed flask is charged with p-toluenesulfonyl chloride (57.20 g, 0.30 mol) (Note 1) to which pyridine (250 mL) (Note 2) is added while stirring is carried out under nitrogen with a magnetic stir bar (Note 3). The reaction flask is placed inside a container to which an ice/water mixture may be added in the event that the reaction becomes too exothermic. 3-Methyl-3-oxetanemethanol (20.4 g, 0.2 mol) (Note 4) is added slowly and stirred for 1.5 hr. The mixture is slowly added to a vigorously (Note 3) stirred mixture of deionized water (700 mL) and crushed ice (700 g) in a 2-L Erlenmeyer flask and allowed to stir for an additional 0.5 hr. The white precipitate is collected on Whatman filter paper 1 and washed with cold water (H20, Note 5). The product is dried under high vacuum and/or phosphorus pentoxide (P205) to obtain the white powder of oxetane tosylate 1 (39.8-44.60 g, 78-87%) (Note 6). 

B. 4-Aaetylpyridine oxime toeylate. Pure E-oxime (27.1 g, 0.20 mol) and p-toluenesulfonyl chloride (47.9 g, 0.22 mol) (Note 6) are added to 100 mL of anhydrous pyridine (Note 7) in a 1-L, round-bottomed flask fitted with a drying tube and a large magnetic stirring bar. The reaction mixture is stirred at 25°C for 24 hr a precipitate of pyridine hydrochloride forms. A 500-mL portion of ice water is added with continued stirring. The initial precipitate dissolves and a voluminous white precipitate soon forms. This is collected by suction filtration, washed with three 150-mL portions of cold water and dried under reduced pressure and over Drierite to constant weight. The yield of pure tosylate, mp 79-81°C (Note 8), is 55.1 g (95%). 

B. Cyalobutyl toaylate. A 500-mL, three-necked, round-bottomed flask fitted with a stirrer and a thermometer is charged with 200 mL of pyridine (Note 5) and 32.3 g (0.448 mol) of cyclobutanol. The solution is stirred and chilled to 0°C, and then 89.8 g (0.471 mol) of p-toluenesulfonyl chloride (Note 5) is added in portions over a 20-min period. The reaction mixture is allowed to warm to room temperature and is stirred for 16 hr. The mixture is recooled to 0°C, and poured into 260 mL of concentrated hydrochloric acid in 800 mL of ice water. The mixture is extracted with three 300-mL portions of ether and the combined ethereal extracts are dried over anhydrous magnesium sulfate. The drying agent is removed by filtration and the filtrate is concentrated on a rotary evaporator. The residue 1s held under high vacuum (0.03 mm) at room temperature for 3 hr to give 93.3 g (92%) of cyclobutyl tosylate as a pale yellow oil (Note 7). 

Alcohol p-Toluenesulfonyl chloride Alkyl p-toluenesulfonate (alkyl tosylate)... 

NMO NMP Nu PPA PCC PDC phen Phth PPE PPTS Red-Al SEM Sia2BH TAS TBAF TBDMS TBDMS-C1 TBHP TCE TCNE TES Tf TFA TFAA THF THP TIPBS-C1 TIPS-C1 TMEDA TMS TMS-C1 TMS-CN Tol TosMIC TPP Tr Ts TTFA TTN N-methylmorpholine N-oxide jV-methyl-2-pyrrolidone nucleophile polyphosphoric acid pyridinium chlorochromate pyridinium dichromate 1,10-phenanthroline phthaloyl polyphosphate ester pyridinium p-toluenesulfonate sodium bis(methoxyethoxy)aluminum dihydride (3-trimethylsilylethoxy methyl disiamylborane tris(diethylamino)sulfonium tetra-n-butylammonium fluoride f-butyldimethylsilyl f-butyldimethylsilyl chloride f-butyl hydroperoxide 2,2,2-trichloroethanol tetracyanoethylene triethylsilyl triflyl (trifluoromethanesulfonyl) trifluoroacetic acid trifluoroacetic anhydride tetrahydrofuran tetrahydropyranyl 2,4,6-triisopropylbenzenesulfonyl chloride 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane tetramethylethylenediamine [ 1,2-bis(dimethylamino)ethane] trimethylsilyl trimethylsilyl chloride trimethylsilyl cyanide tolyl tosylmethyl isocyanide meso-tetraphenylporphyrin trityl (triphenylmethyl) tosyl (p-toluenesulfonyl) thallium trifluoroacetate thallium(III) nitrate... 

Sometimes, the sulfonyl chloride is dissolved in an indifferent, water-immiscible solvent. Thus, tosylation of cellulose was brought about by treating alkali-cellulose with a solution of p-toluenesulfonyl chloride in carbon tetrachloride,6061 benzene,61-64 or toluene.56 The number of... 

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