Dimethyl sulfide and N-chlorosuccinimide

Treatment of various 2-aminopyridines and of 1-aminoisoquinoline with dimethyl sulfide and N-chlorosuccinimide gives the corresponding salt which on deprotonation with base provides a sulfilimine (e.g. 98) (76JCS(P1)2166>. Oxidation of the latter with m-chloroperben-zoic acid gives the corresponding nitroso heterocycle (Scheme 85). 

Dimethyl sulfide and chlorine or, better still, dimethyl sulfide and N-chlorosuccinimide, form a system capable of the selective dehydrogenation of alcohols to aldehydes or ketones. The intermediates, such as (013)28 C1 Cr, react with bases according to the scheme in equation 25 [720],... 

OxUatiou of primary and secondary alcohals to carbonyl compounds. Corey and Kim report that the complex of N-chlorosuccinimide and dimethyl sulfide is somewhat superior to the complex of dimethyl sulfide and chlorine (this volume) for oxidation of primary and secondary alcohols the formation of hydrogen chloride is avoided and yields are generally higher. The procedure is illustrated for the oxidation of 4-r-butyl-cyclohexanol (2) to 4-r-butylcyclohexanonc (4). The complex (1) is prepared by addition of dimethyl sulfide (4.1 mmole) to a stirred solution of NCS (3.0 mmole) in toluene at 0° under argon. The mixture is cooled to -25° and a solution of 4-r-butylcyclo-hexanol (2.0 mmole, mixture of cis and trans) in toluene is added dropwise. The stirring is continued for 2 hr. at — 25° and then triethylamine (3.0 mmole) in toluene is added dropwise. The ketone (4) is obtained in almost quantitative yield. As in oxidation with the complex of dimethyl sulfide and chlorine, an intermediate sulfoxonium complex (3) is involved. 

Dimethyl(succinimido)sulfonium fluorosulfate 2, easily prepared from /V-chlorosuccinimide (1), dimethyl sulfide, and methyl fluorosulfate, reacted with 1-dialkylaminocycloalkenes 3 to give fair yields of (2-dialkylaminocycloalk-l-enyl)dimethylsulfonium fluorosulfates 4 or their thermally rearranged allylic isomers 5.22 23 At elevated temperatures 4 or 5, respectively, reacted with nucleophiles Nu to give c -bicyclo[n.l.O]alkanes 8 or 9 via (Z,Z)-2-aminoallyl cation 6 or trans-bicyclo[n.l. 0]alkanes 12 via ( , Z)-2-aminoallyl cation 10, in fair to excellent yield.23 " 42 Normally, ra-annulated cyclopropylamines 8, resulting from kinetically preferred attack of... 

Vilsmaier and Spriigel obtained this complex in 85% yield by the reaction of N-chlorosuccinimide with dimethyl sulfide in methylene chloride at 0°. It was shown to... 

Selective conversiou of allylic and benzylic alcohols into halides It was noted above that allylic or benzylic alcohols are not oxidized by the N-chlorosuccinimide-dimethyl sulfide reagent but instead are converted into chlorides. Corey et al. now report that this procedure can be used to form allylic and benzylic chlorides in high yield if the sulfoxonium intermediate corresponding to (3, above) is allowed to decompose in methylene chloride without addition of a tertiary amine. For example, the allylic or benzylic alcohol is treated with the complex of N-chlorosuccinimide-dimethyl sulfide as above in methylene chloride and then allowed to stand for 4 hr. at - 25°. In the case of benzhydroi [(CfcH5)2CHOH], benzhydryl chloride can be obtained in > 95% yield. 

A mixture of N-chlorosuccinimide and dimethyl sulfide oxidizes alcohols to ketones under very mild conditions and in high yields. The treatment of 4-tm-butylcyclohexanol with this mixture in toluene at 0-25 °C, followed by the addition of triethylamine in toluene, results in a 90-93% yield of 4-tert-butylcyclohexanone [721]. 

The reagent was used by Corey and Kim3 in an improved synthesis of prostaglandins. Thus oxidation of the hydroxy acid (5) to the keto acid (6) was effected in > 90% yield with use of N-chlorosuccinimide-dimethyl sulfide. The oxidation had been carried out previously with Jones reagent at —20° in about 70% yield. The carboxyl function... 

The alcohol (1.5 L, 208 g, 280 mmol) in THF is charged to a jacketed flask followed by dimethyl sulfide (37 g, 590 mmol) and diisopropylethylamine (47 g, 364 mmol). The solution is cooled to approximately -13 °C. 7V-Chlorosuccinimide (NCC 71 g, 532 mmol) is dissolved in THF (240 mL) and added to the flask at a rate so as to maintain the internal temperature at -11 to -13 °C. The mixture is then stirred at -15 5 °C for 3 h. Isopropyl acetate (3 L) is added followed by 0.5 N NaOH (1.2 L). The mixture is warmed to room temperature and stirred for 1 h. The organic layer is washed with 5% NaCl (2 x 600 mL) and brine (2 x 600 mL). The product layer is concentrated under vacuum to obtain, at first, a yellow amorphous solid which when dried under high vacuum turns into a white foam. Slurrying the solid in warm water followed by filtration and drying afforded 196 g (94%) of the 3-ketomacrolide as a white solid after trituration with 10% EtOAc/heptane. 

The starting material, l,3-dibenzyloxy-2-propanol 265, is easily oxidized to the ketone 408 using N-chlorosuccinimide and dimethyl sulfide. Compound 408 was smoothly converted into the epoxide 409. The epoxide ring was opened by the attack of benzylate anion at the least hindered site to produce 2-benzyloxymethyl-l,3-dibenzyloxy-2-propanol (410), which was activated as the thiomethyl ether system 411 using acetic anhydride in DMSO. The thiomethyl ether is readily activated by iodine, allowing nucleophilic attack at the methylene position. As a result, compound 411 was... 

Chlorination of Aromatic Compounds. NCS has also been used for the chlorination of pyrroles and indoles however, the reaction is less straightforward than when NBS and N-Iodosuccinimide are used. In the chlorination of 1-methylpyrrole, it has been demonstrated that basic conditions (NaHCOs, CHCI3) lead to the formation of 1-methyl-2-succinimidylpyrrole (eq 11). In the presence of catalytic amounts of perchloric acid, thiophenes and other electron-rich aromatic compounds have been chlorinated with NCS. (N-Chlorosuccinimide-Dimethyl Sulfide is used for the selective -substitution of phenols.)... 

A mixture of 1-morpholinocyclohexene, N-chlorosuccinimide, and dimethyl sulfide in methylene chloride stirred 2 days at room temp. 2-morpholino-3-chloro-cyclohexene. Y 77%. F. e. s. E. Vilsmaier, W. Spriigel, and K. Gagel, Tetrah. Let. 1974, 2475. 

Dimethyl sulfide allowed to react with f rf-octylamine in methylene chloride in the presence of 1-chlorobenzotriazole crude N-r rr-octyl-S,S-dimethylimino-sulfonium chloride. Y 90%. F. e., also with N-chlorosuccinimide, and related reactions s. A. D. Dawson and D. Swern, J. Org. Chem. 42, 592 (1977). 

Olefinic aldehydes have been synthesized by a variety of methods including oxidation of the corresponding primary alcohols with the chromium trioxide-pyridine complex 195—197) or N-chlorosuccinimide-dimethyl sulfide complex 198), heating a primary alken-l-yl mesylate with dimethylsulfoxide 199), or by alkylation of the lithium salt of 5,6-dihydro-2,4,4,6-tetramethyl-l,3-(4H)-oxazine with an alkynyl iodide followed by sodium borohydride reduction and acid hydrolysis (200). 

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