Reactions with N-chlorosuccinimide

An attempt to directly convert hyellazole (245) to 6-chlorohyellazole (246) by reaction with N-chlorosuccinimide in the presence of a catalytic amount of hydrochloric acid led exclusively to 4-chlorohyellazole. On the other hand, bromination of 245 using NBS and a catalytic amount of hydrobromic acid gave only the expected 6-bromohyellazole (733). Alternatively, a direct one-pot transformation of the iron complex 725 to 6-bromohyellazole (733) was achieved by reaction with an excess of NBS and switching from oxidative cyclization conditions (basic reaction medium) to electrophilic substitution conditions (acidic reaction medium). Finally, a halogen exchange reaction with 4 equivalents of cuprous chloride in N,N-dimethylformamide (DMF) at reflux, transformed 6-bromohyellazole (733) into 6-chlorohyellazole (246) (602) (Scheme 5.73). 

Chlorination of 5-hydroxyquinoxaline 1,4-dioxide in methylene chloride gives the 6,8-dichloro derivative, but reaction with N-chlorosuccinimide yields 8-chloro-5-hydroxyquinoxaline dioxide. Bromination in acetic acid gives the 6,8-dibromo derivative.195 15 Side-chain bromination is observed, however, when 2,3-dimethylquinoxaline 1,4-dioxide reacts with bromine in dioxane 2,3-bis(bromomethyl)quin-oxaline 1,4-dioxide is formed.195c... 

The latter, on reaction with methylamine yielded via the P-epoxide 373, the trans-a aminoalcohol 374, which was N-acylated to the amide 375. Acid-catalysed dehydration of the tertiary alcohol 375, led to the olefin 375, from which the key radical precursor, the chlorothioether377 was secured in quantitative yield by reaction with N-chlorosuccinimide. In keeping with the earlier results recorded for structurally related compounds, 377 on heating in the presence of ruthenium dichloride and triphenylphosphine also underwent a 5-exo radical addition to generate the cyclohexyl radical 378 which recaptured the chlorine atom to furnish the a-chloro-c/5-hydroindolone 379. Oxidation of thioether 379 gave the corresponding sulfoxide 380, which on successive treatment with trifluoroacetic anhydride and aqueous bicarbonate led to the chloro-a-ketoamide 381. The olefin 382 resulting from base induced dehydrochlorination of 381, was reduced to the hydroxy-amine 383, which was obtained as the sole diastereoisomer... 

Oxidation of alcohols under extremely mild conditions can be effected using a procedure that is mechanistically related to the DMSO method. Dimethyl sulfide is converted to a sulfonium derivative by reaction with N-chlorosuccinimide. This sulfur species reacts readily with alcohols, generating the same kind of alkoxysul-fonium salts that are involved in the DMSO procedures. In the presence of mild base, elimination of dimethyl sulfide completes the oxidation. ... 

Arylmethylamines can be oxidized to the corresponding arylamides by formation of a Schiff base with 2,6-di-t-butylbenzoquinone and base-catalysed oxygenation. Allenic alcohols are oxidized to allenic amides by nickel peroxide at -20 °C in ethereal ammonia. N-Alkyl-amides can be prepared from aldehydes in a four-step procedure consisting of imine formation and subsequent reactions with N-chlorosuccinimide, potassium cyanide, and finally alcoholic HCl. ... 

Chlorination occurs on reaction with N-chlorosuccinimide (NCS), SO2CI2, or SnCl4/Pb(OAc)4, bromination with NBS, Br2/HOAc, or Br2/48% HBr, iodination with I2/HNO3/H2O [63] ... 

Not surprising, the most prevalent synthetic utility is the assembly of the pyrrolidine ring. N-Chloroamine 27 was obtained by treatment of N-methyl-2-cyclopentylethylamine (26) with N-chlorosuccinimide. Under classic Hofmann-Loffler-Freytag reaction conditions, 27 was rearranged either thermally or by UV irradiation in sulfuric acid to bicyclic amine... 

The a -halosulfone, required for the Ramberg-Backlund reaction, can for example be prepared from a sulfide by reaction with thionyl chloride (or with N-chlorosuccinimide) to give an a-chlorosulfide, followed by oxidation to the sulfone—e.g. using m-chloroperbenzoic acid. As base for the Ramberg-Backlund reaction have been used alkoxides—e.g. potassium t-butoxide in an etheral solvent, as well as aqueous alkali hydroxide. In the latter case the use of a phase-transfer catalyst may be of advantage. ... 

Reduction of iV-(3-bromopropyl) imines gives a bromo-amine in situ, which cyclizes to the aziridine. Five-membered ring amines (pyrrolidines) can be prepared from alkenyl amines via treatment with N-chlorosuccinimide (NCS) and then BusSnH. " Internal addition of amine to allylic acetates, catalyzed by Pd(PPh3)4, leads to cyclic products via a Sn2 reaction. Acyclic amines can be prepared by a closely related reaction using palladium catalysts. Three-membered cyclic amines (aziridines)... 

The reaction of nitrones of the 3-imidazoline series (295) with bromine and amyl nitrite, in the presence of base, gives a-tribromomethyl-(296) and a-hydroxyaminomethyl derivatives (297) (538). Bromination of nitrones (295) with N -bromosuccinimide (NBS) in CCI4 or bromine in methanol leads to the formation of a-bromoalkyl (298 a,b, Hal = Br) and a-dibromomethyl (299) nitrones (539-541). The reaction with iodine in methanol gives the mono iodo derivative (300) (541). The reaction with A-chlorosuccinimide (NCS) in CCI4 leads to a-chloroethyl nitrones (298b, Hal = Cl) and a,a-dichloromethyl nitrones (301) (Scheme 2.118) (225). 

Whenever only primary amines need to be derivatized, fluorescamine often constitutes the reagent of choice. Fluorescamine, although nonfluorescent itself, can react with primary amines forming highly fluorescent pyrrolinones (139-144). Aliphatic primary amines favor derivatization reaction at pH 8-9, whereas primary aromatic amines exhibit optimal reactivity at pH 3-4. Secondary amines are also fully reactive with fluorescamine but their products do not fluoresce. However, secondary amines can be detected with fluorescamine if they are converted to primary amines by oxidation with N-chlorosuccinimide prior to their fluorescamine derivatization (145, 146). Alcohols can also interact with fluorescamine but this reaction is reversible as a result, alcohols just slow down the reaction rate of fluorescamine with primary amines. On the other hand, tertiary amines and guanidines are not reactive at all with fluorescamine. 

Toluenesulfenyl chloride has been prepared by the action of chlorine on a solution of -toluenethiol or />-tolyl disulfide in anhydrous carbon tetrachloride.2,3 Benzenesulfenyl chloride has also been obtained by the interaction of hydrogen chloride and N,N-diethylbenzenesulfenamide 4 and by reaction of benzenethiol with N-chlorosuccinimide.6 A comprehensive review dealing with sulfenyl halides and related compounds is available.6... 

Since fluorescamine reacts only with primary amino groups, secondary amino acids do not give a fluorescent product with this reaction. A method for converting secondary amino acids into primary amines has been described for analysis using fluorescamine [87], and is based on treatment of the amino acid with N-chlorosuccinimide. The reaction involves an oxidative decarboxylation of the amino acids. This method has been incorporated into the automatic analysis of amino acids with fluorescamine [88]. The fluorescence spectra and the sensitivities are similar to those of the derivatives of the primary amino acids. 

Chlorothieno[3,2-<7]pyrimidin-4(3//)-one 190a (R2 = Cl, R3 = H) was converted to the 8-bromo derivative 285 by heating at 80°C in a mixture of bromine and acetic acid (88USP4725599). Thieno[3,2-d]pyrimidinedione 270 (R = 2 - F, R1 = 4 - Br, R2 = R3 = H) was chlorinated at position 6 by heating at 60°C with sulfuryl chloride in carbon tetrachloride. The reaction worked equally well with N-chlorosuccinimide instead of sulfuryl chloride (93MI1). 

Monochlorination of the morpholine enamine of AT-methylpiperidin-4-one with N-chlorosuccinimide, followed by treatment with sodium cyanide, yields the exo-cyanoa-za[3.1.0]bicyclohexane 40 in contrast, the dichlorinated enamine affords the endo-cyano compound 41 in this reaction (equation 27)48. 

N-Iodosuccinimide, 1, 510-511 10, 216. The leagent can be prepared by reaction of N-chlorosuccinimide with sodium iodide in acetone. Filtration from NaCI and evaporation of the solvent provides material comparable to that prepared according to the literature. ... 

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... 

Vilsmaier, E., Spruegel, W. Halo thioethers. I. Reaction of thioethers with N-chlorosuccinimide. Liebigs Ann. Chem. 1971, 747,151-157. 

Ohkata, K., Mase, M., Akiba, K. Reaction of silyl enol ethers with N-chlorosuccinimide trapping of the siloxycarbinyl cation by an azide anion. J. Chem. Soc., Chem. Common. 1987,1727-1728. 

With this experience in hand, the amine hydrochloride IQ was transformed into the aminonitrile 2A as shown in Figure 4. This entire sequence was carried out on an approximate 0.5 mole scale via five separate reactions without isolation of intermediates to give a 67% overall yield of aminonitrile 1A based on amine IQ. Thus, the amine hydrochloride IQ was neutralized with concentrated potassium hydroxide, and the liberated free amine Q was taken up in ether. Treatment of this solution with N-chlorosuccinimide (NCS) gave a solution of the N-chloroamine 11. Further addition of ethanolic potassium hydroxide effected dehydrochlorination. The resultant bicyclic imine 12. in ethanolic ether was sequentially treated with aqueous sodium bisulfite and then solid sodium cyanide. The desired aminonitrile 1A was isolated as a distillable liquid. 

Recent research demonstrated that these problems can be circumvented by a simple change of the order of synthetic steps ketones 8 were first transformed to enamines 9 in a conventional manner. The allylic chlorine was then introduced with one equivalent of N-chlorosuccinimide to give chloroenamine 10. While for R R enamines 9 were usually obtained as a mixture of regioisomers, their reaction with A-chlorosuccinimide often... 

As well as selenenyl halides, N-phenylselenosuccinimide (N-PSS) and N-phenyl-selenophthalimide (N-PSP) are widely used as powerful selenenylating reagents in organic synfhesis. N-PSS and N-PSP are conveniently synthesized by reaction of diphenyl diselenide with N-chlorosuccinimide and N-chlorophthalimide, respectively (Scheme 15.12) [39]. 

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