Chlorination N-Chlorosuccinimide

Synthetic procedures are available for the preparation of fluoro, chloro, bromo and iodo compounds from the corresponding lithio derivatives. Perchloryl fluoride (FCIO3), N-chlorosuccinimide, bromine and iodine are examples of reagents which can be used to introduce fluorine, chlorine, bromine and iodine, respectively. 

Reduction of 5//-6,7-dihydrodibenz[t, e]azepine-5,7-dione (31) with lithium aluminum deuteride followed successively by ring chlorination with N-chlorosuccinimide and dehydrochlorination. affords [5,5,7-2H3]-5//-dibenz[r, >]azepine (32).117... 

Chlorination with N-chlorosuccinimide at the activated indole 2-position gives the corresponding chloro... 

Soufiaoui reported that arylnitrile oxides 10 can be generated under microwaves not only from aromatic oxime chlorides, such as 174, by the action of alumina (Method A) but also from aryloximes, such as 176, by the addition of a chlorination agent, N-chlorosuccinimide (NCS), supported on alumina (Method B) (Scheme 9.54) [29a]. Both methods afforded identical cydoadducts in similar yields - when indene was used as the dipolarophile the yield was 86%. In the absence of alumina, method B fails (reagents are less reactive and decompose) and method A does not yield any cydoadduct but a dimer of the dipole. 

For small-scale work the chlorination is also conveniently carried out by N-chlorosuccinimide (Kenner, Todd and Weymouth, J. Chem. Soc. 1952, p. 3575). In this case no acid by-product is obtained. This modification is discussed in Chapter iv. 

Secondary allylic amines 184 have been prepared from aldehydes 181 (R1 = H, Me or Ph R2 = Me, Et or H) by the following sequence treatment with an amine R3NH2 (R3 = i-Pr, t-Bu, cyclohexyl or PhCH2) yields an imine 182, which is chlorinated by N-chlorosuccinimide. Dehydrochlorination of the resulting chloro compound with potassium t-butoxide gives an allylic imine 183, which is reduced to the product by means of methanolic sodium borohydride191. 

Many compounds containing one or more N—X bonds show unstable or explosive properties (and are also oxidants), and this topic has been reviewed [1]. Difluoroamino compounds, ranging from difluoramine and tettafluorohydrazine to polydifluoroamino compounds, are notably explosive and suitable precautions have been detailed [2,3], Preparative scale A-chlorination of ly and 2y amines by passing them over N-chlorosuccinimide is described. In presence of alumina, ly amines give the N,N -dichloro derivatives. The products must be handled with... 

Cyclopentenylacetic acid when treated with sulfur monochloride, Hiinig s base and N-chlorosuccinimide in tetrahydrofuran gave trichlorocyclopenta[l,2]-dithiole ester 104, a product of heterocyclic ring formation, chlorination and dehydrochlorination and, unexpectedly, the conversion of the acid in THF into its 4-chlorobutyl ester (1999JCS(P1)1023 Scheme 52). 

A reaction with seven-membered cyclic oximes proceeded similarly to give cyclopenta-l,2,3-dithiazoles 136 and 137 (1993JCS(P1)769 Scheme 69). For chlorination, up to 15 equivalents of sulfur monochloride were used and polychlorination was assisted by N-chlorosuccinimide. 

Another methodology for the in situ preparation of nitrile oxide is the dehydro-halogenation of hydroxymoyl chlorides vrith triethylamine. Hydroxymoyl chlorides are accessible by the reaction of aldoximes vrith chlorinating agents such as NCS (N-chlorosuccinimide). Isoxazolines of C50 and C70 [293-295] with R = Ph, alkyl, 4-C5H4OCH3 4-C5H4CHO, amino acid [305], dialkoxyphosphoryl [296, 297] or ferrocene [298] have been synthesized in ca. 20 0% yields. The latter reaction is slower than the dehydration of nitroalkanes and requires one equivalent of hydroxymoyl chloride whereas excess nitroalkane is necessary for an optimum reaction [293]. 

Thiepane (35) has been converted to 2-acetoxythiepane (137) by a homolytic mechanism using f-butyl peracetate in the presence of a copper(I) ion catalyst (67JCS(C)1130). Similarly, a-chlorination of thiepane (35) by N- chlorosuccinimide (NCS) to yield 2-chlorothiepane (132) probably occurred by a free radical pathway (Scheme 27) (69JHCU5). 

When 2,2-disubstituted 1,3-dioxolanes were employed, mono- or poly-chlorination of the side chain was observed on the carbon atom a to the acetal grouping. Incidentally, it should be noted thatN-bromo-succinimide, N-chlorosuccinimide, and trichlorotetrahydrotriazine-trione were found to be effective for the preparation of bromoacetates from O-ethylidene derivatives this might be useful when O-benzyli-dene derivatives are not readily available, or when a problem arises due to the fact thatO-benzoyl groups are, in general, more difficult to remove than O-acetyl groups. 

A number of other methods exist for the a halogenation of carboxylic acids or their derivatives.134 The acids or their chlorides or anhydrides can be a chlorinated by treatment with CuCl in polar inert solvents (e.g., sulfolane).135 Acyl halides can be a brominated or chlorinated by use of N-bromo- or N-chlorosuccinimide and HBr or HC1.136 The latter is an ionic, not a free-radical halogenation (see 4-2). Direct iodination of carboxylic acids has been achieved with L-Cu(II) acetate in HO Ac.137 Acyl chlorides can be a iodinated with L and a trace of HI.138 Carboxylic esters can be a halogenated by conversion to their enolate ions with lithium N-isopropylcyclohexylamide in THF and treatment of this solution at - 78° with I2138 or with a carbon tetrahalide.139 Carboxylic acids, esters, and amides have been a fluorinated at -78°C with F2 diluted in Ni.,4°... 

Sulfoxides can be chlorinated in the a position141 by treatment with Cl ,142 TsCl,141 N-chlorosuccinimide,144 or PhICl2,145 all in the presence of pyridine, or with t-BuOCI and KOAc (or pyridine).146 All these methods involve basic conditions. The reaction can also be accomplished in the absence of base with S02C12 in CH2CI2.147 The bromination of sulfoxides with bromine145 and with N-bromosuccinimide-bromine148 have also been re-... 

Monosubstitution at a occurs in 255 with N-bromosuccinimide, N-chlorosuccinimide, and 25% nitric acid at 0° disubstitution (a a ) occurs with bromine or chlorine in acetic acid, thionyl chloride, chlorosulfonic acid, and 70% nitric acid and tetrasubstitution (a a bb ) is obtained with 90% nitric acid 254b behaves similarly. Tetra-cyanoethylene forms -complexes with 255 and 328,340 and the latter compound is slowly converted on standing to a C-substituted derivative with loss of HCN. 

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... 

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... 

Several reactive chloro compounds have been used to attempt to effect the controlled monochlorination of aromatic amines. One such reagent is N-chlorosuccinimide, with which the chlorination of aniline, for example, can be largely restricted to monosubstitution, although a mixture of isomers (orthopara, 1.9 1) is obtained.24 One approach to the achievement of specific ortho chlorination is illustrated by the synthesis of o-chlorobenzanilide (Expt 6.61), readily hydrolysable to o-chloroaniline. The anilide is formed, by a type of Swi mechanism indicated below, when AT-phenylhydroxylamine is benzoylated and the product is treated with thionyl chloride.25 The reaction has been successfully applied to several substituted JV-phenylhydroxylamines, prepared by the controlled reduction of the corresponding substituted nitro compounds (cf. Expt 6.87). 

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... 

---