Tosyl chloride/potassium carbonate

Keywords alkyl tosylate, tosyl chloride/potassium carbonate... 

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). 

The synthesis of 2C-T-17 R required starting with the S isomer of secondary butanol. The S 2-butanol in petroleum ether gave the lithium salt with butyllithium which was treated with tosyl chloride (freshly crystallized from naphtha, hexane washed, used in toluene solution) and the solvent was removed. The addition of 2,5-dimethoxythiophenol, anhydrous potassium carbonate, and DMF produced S 2,5-dimethoxyphenyl s-butyl sulfide. The conversion to R 2,5-dimethoxy-4-(s-butyl-thio)benzaldehyde (which melted at 78-79 °C compared to 86-87 °C for the racemic counterpart) and its conversion in turn to the nitro-styrene, S -2,5-dimethoxy-4-(s)-butylthio-B-nitrostyrene which melted at 70-71 °C compared to 68-69 °C for the racemic counterpart, followed the specific recipes above. The preparation of the intermediates to 2C-T-17 S follows the above precisely, but starting with R 2-butanol instead. And it is at these nitrostyrene stages that this project stands at the moment. 

The tosyl compound reacts with aldehydes in the presence of potassium carbonate to yield 5-alkyl- or 5-aryl-oxazoles, the intermediate dihydrooxazoles (which can be isolated) eliminating toluene-p-sulfinic acid (Scheme 30). Use of acyl chlorides in place of aldehydes leads to 4-tosyloxazoles (288). Furthermore, alkylation of tosylmethyl isocyanide with an alkyl halide RfX, followed by treatment with an aldehyde R2CHO, yields a 4,5-disubstituted oxazole (289). A related reaction is that of A-tosylmethyl-iV -tritylcarbodiimide with aromatic aldehydes under phase-transfer catalysis to yield 2-tritylaminooxazoles which are readily converted into 2-amino-5-aryloxazoles (equation 117) (81JOC2069). 

Scheme 6 describes the most important reactions of the perimidinespirocyclo-hexadienone 1. A treatment of 1 (R = H) in dimethylsulfoxide (DMSO) solution with methyl iodide in the presence of potassium carbonate affords the A-m ethyl derivative la (R = Me), whereas use of an excessive amount of methyl iodide in this reaction leads to the A,A -dimethyl derivative of the ring-closed tautomer.4,7 By contrast, acylation of la by acetic anhydride or its tosylation by treatment with p-toluenesulfonyl chloride results in the formation of the respective derivatives of the ring-opened tautomeric form lb. 

Another potential approach towards 1 was reported by Seido et al. utilizing an asymmetric reduction of the ketone (57 Scheme 15) as the key step. Acylation of the lithium enolate of methyl phenylacetate with the imidazolide, obtained by treatment of the acid 56 with A, V -carbonyldiimidazole, gave the ketoester 57 in 66.4% yield. Asymmetric reduction of 57 with [RuI(/7-cymene)(5)-binap]I, tin chloride, and cam-phor-lO-sulfonic acid in methanol at 80 °C afforded the alcohol 58 as a mixture of syn and anti forms in 87.4% yield. The ratio of syn to anti isomers was 76.3 23.7 and the enantiomeric purity of each form was 95.6% ee and 97.8% ee, respectively. Tosylation of 58 with p-toluenesulfonyl chloride and pyridine in the presence of catalytic amounts of DMAP yielded a diastereomeric mixture of tosylate 59 in 61.8% yield. Deprotection of the /V-Cbz group in 59 by hydrogenation over 5% Pd-C followed by cyclization of the resulting amino tosylate 60 with potassium carbonate in methanol furnished methylphenidate as a mixture of erythro and threo isomers in a 7 3 ratio and 77.5% yield. 

Two series of reactions were carried out on this compound. In one of these, the tosyl amino alcohol 418 was reacted with /3-chloropropionyl chloride followed by oxidation with Jones reagent to give the tosyl keto amide 419. Elimination of HC1 with potassium carbonate in methylene chloride and cyclization of the acrylamide with Meerwein s reagent gave the N-tosyl keto lactam 420. This compound was also prepared by the previously discussed route (203). 

The direct transformation of 2-amino alcohols to V-tosyl aziridines can be achieved in moderate to good yields using potassium hydroxide and tosyl chloride in water/dichloromethane. This procedure works well for small amino alcohols. Ehgher substituted amino alcohols give better yields using a two-step procedure formation of the N, 0-ditosylate followed by cyclization with potassium carbonate in acetonitrile. 

A method has been described for the preparation of carbodiimides 1699 by dehydration of ureas 1696 with p-tosyl chloride under solid-liquid phase-transfer catalytic (PTC) conditions using solid potassium carbonate as a base and a lipophilic quaternary ammonium salt as a catalyst. The method is generally applicable for the synthesis of disubstituted carbodiimides, but is especially useful for un-symmetrically substituted carbodiimides. Yields of the resulting carbodiimides 1699 vary depending on the solvent (usually used at reflux temperature) in benzene or toluene yields of 66-98% are achieved, while in chloroform they are only 30-50% [1281]. 

Preparation by a three-step synthesis first, tosylation of a-methoxyphloroaceto-phenone with p-tolnenesulfonyl chloride in the presence of potassium carbonate in refluxing acetone for 4 h. Dimethyl sulfate and potassium carbonate were then added and the mixture refluxed for 36 h more. Finally, saponification of the residue isolated by distillation with refluxing 5% methanolic potassium hydroxide for 4 h (42%) [4861]. 

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