Chlorination, chlorosuccinimide

V-Chlorosuccinimide [128-09-6] mp 150—151°C, forms orthorhombic crystals and has a chlorine-like odor it is prepared from succinimide and hypochlorous acid (114,115). Because of its powerhil germicide properties, it is used ia disiafectants for drinking water. Like its bromine derivative, it is also a halogenating agent. 

Treatment of pyrrole, 1-methyl-, 1-benzyl- and 1-phenyl-pyrrole with one mole of A -bromosuccinimide in THF results in the regiospecific formation of 2-bromopyrroles. Chlorination with IV-chlorosuccinimide is less selective (8UOC2221). Bromination of pyrrole with bromine in acetic acid gives 2,3,4,5-tetrabromopyrrole and iodination with iodine in aqueous potassium iodide yields the corresponding tetraiodo compound. 

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. 

Another decarboxylation reaction that employs lead tetraacetate under milder conditions, has been introduced by Grob et alJ In that case A-chlorosuccinimide is used as chlorinating agent and a mixture of A,A-dimethylformamide and acetic acid as solvent. 

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... 

Controlled chlorination with A-chlorosuccinimide results in the formation of square pyramidal RhHCl2(PPr3)2 and planar RhCl2(PPr 3)2 (Figure 2.65). 

A. Chlorinating agents Sodium hypochlorite solution A-Chlorosuccinimide Chloramine-Tb... 

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. 

Most of the esters of phosphorofluoridic acid hitherto described in this monograph can be readily prepared on a small scale in this way. It may be emphasized that chlorination by 31-chlorosuccinimide is for this purpose more satisfactory than by gulphuryl chloride,2 as with the latter reagent an acid medium is produced ... 

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]. 

Bugge used PMR spectroscopy to confirm the structures of the products obtained on chlorination (iV-chlorosuccinimide), acetylation... 

Recently Bugge studied the reactivities of thienothiophenes 1 and 2 and thiophene by the competitive method, utilizing SnCl4-catalyzed acetylation with acetic anhydride, Vilsmeier formylation and chlorination with iV-chlorosuccinimide. Thienothiophenes 1 and 2 are always more reactive than thiophene. In acetylation the reactivities of 1 and 2 are similar, while in formylation and chlorination thienothiophene 2 is somewhat more reactive than isomer 1 (Table V). 

With one equivalent of IV-chlorosuccinimide (NCS) in acetic acid at 25°, thienothiophene 1 gives the initial thienothiophene 1 (11%), 2-chloro- (78%) and 2,5-dichlorothieno[2,3-6]thiophene (10%), while a 70% yield of 2,5-dichlorothieno[2,3-6]thi(q)hene is produced with two equivdents of NCS. Similar results were obtained from thienothiophene 2 with one and two equivalents of NCS. About 0.4% 3-chlorothieno[2,3-6]thiophene was detected by gas-liquid chromatography among the chlorination products of 1. The same amount of /9-isomer is found in thiophene chlorination products. In the case of thienothiophene 2, the corresponding /9-isomer was not observed in the reaction products. To identify 3-chloro-substituted thiophene and thienothiophenes 1 and 2 in reaction mixtures, these compounds were prepared independently from the corresponding 3-bromo derivatives by Uthiation followed by chlorination at —70°. 

For the formation of 5-chloropyrimidines, AT-chlorosuccinimide is normally the reagent of choice, but several other electrophilic chlorine sources including chlorine gas or sulfuryl chloride can be used <1994HC(52)1>. For example, the chlorination of 4-(trifluoromethyl)-2(l//)-pyrimidinone 59 with ferric chloride and sulfuryl chloride in acetic acid gave the 5-chloro derivative 60 in 80% yield <2004EJ03714>. 

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