Chlorinations A -chlorosuccinimide

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. 

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... 

Hydroximoyl halides (4) are conveniently prepared by halogenation of the respective aldoximes (5), for which a number of halogenating agents such as chlorine (38), ferf-butyl hypochlorite, A -chlorosuccinimide (NCS) (39), or A -bromosuccin-imide (NBS) (40) have been employed. A plausible mechanistic course involves Hal addition and proton loss to give an a-halonitroso compound, often observed as a transient blue-green color, as shown for the chloro case (Scheme 6.1). 

During an investigation of the synthesis of oxazole-4-carboxylates, Shapiro reported that chlorination of amino[(phenylthio)methyl]malonate derivatives 91 with A -chlorosuccinimide (NCS), followed by treatment with Hunig s base, afforded the oxazolines 93. The oxazolines 93 were then converted to the respective oxazole-4-carboxylates 94-97 through decarbomethoxylation and elimination of thiophenoxide in the presence of methyl iodide. Methyl iodide traps the ejected thiophenoxide that would otherwise demethylate the oxazole-4-carboxylate (Scheme 8.31). " ... 

Over recent years, the electrochlorination of a wide range of substrates has been reported. The direct halogenation of benzene has been studied at Pt and Rh electrodes and the in situ spectro-electrochemical monitoring of the process with confocal microprobe Raman methods allowed optimization of the reaction conditions [80]. Toluene has been chlorinated at DSAs and the kinetics of this process have been explored in detail [81]. The electrochlorination of 1,4-dimethoxy-2-tert-butylbenzene has been reported in CCI4 and in acetonitrile environments [82]. A difference in mechanism has been proposed to explain the observation of l,4-dimethoxy-2-tert-butyl-5-chlorobenzene and l,4-dimethoxy-2-tert-butyl-6-chlorobenzene, respectively, as the main products. Succinimide is electrochlo-rinated to give A -chlorosuccinimide at platinum electrodes, but the process has been reported to be relatively inefficient due to side reactions (when compared... 

A tetrahydropyrido[3,4-/)]pyrazine nucleus was constructed from 2,3-dimethylpyrazine 687 by chlorination with A-chlorosuccinimide (NCS) to give 2,3-bis(chloromethyl)pyrazine 688, followed by cyclization with diethyl acet-amidomalonate to pyridopyrazine 689. Hydrolysis and decarboxylation of 689 in hydrochloric acid, then esterification by action of thionyl chloride in methanol gave methyl 5,6,7,8-tetrahydropyrido[3,4-. ]pyrazine-7-carboxylate hydrochloride 690 (Scheme 32) <2003BMC433>. 

Bromofluorination of dodec-2-ene, styrene, and methyl undec-10-enoate are carried out using similar conditions but using l,3-dibromo-5,5-dimethylhydantoin instead of A-halosuc-cinimide however, chlorofluorination with A-chlorosuccinimide as a chlorinating reagent is not successful at all and starting alkenes are recovered unchanged.336... 

A mixture of (E)- and (Z)-chlorostyrenes was obtained from the above ylide, with R = Ph and R = H once again, (dichloroiodo)benzene was differentiated from other chlorinating agents, since these yiides with A-chlorosuccinimide delivered the ( )-isomer with high selectivity. 

Synthetic procedures are available for the preparation of fluoro (e.g., 2-lithio-l-methyl-5-octylpyrrole with fV-fluoro-iV-(phenylsulfonyl)benzenesulfonamide <2003JFC(124)159>), chloro, bromo, and iodo compounds from the corresponding lithio derivatives, for example, 2-iodobenzo[A]furan via lithiation of the heterocycle then reaction with iodine <2002JOC7048>. Perchloryl fluoride (FCIO3), A-chlorosuccinimide, bromine, and iodine are examples of reagents which can be used to introduce fluorine, chlorine, bromine, and iodine, respectively. 

Chloroselenepine 84 was obtained from ketone 83 by reduction of a Grignard reagent, followed by chlorination with A-chlorosuccinimide in good yields <2001HAC317>. 

The methanesulfonyl derivatives are more usually produced by reaction of appropriate methylthiopurines with chlorine in aqueous or aqueous alcoholic solution at low temperatures, or with A-chlorosuccinimide in methanol-DMF (62CPB1075). Gentle oxidation of methylthiopurines, e.g. 6-methylthiopurine, with restricted amounts of hydrogen peroxide can lead to intermediate methylsulfinylpurines. Thus 2-methylthioadenine gave 6-amino-2-methylsulfinylpurine (203) (63JOC2560). 

An interesting reactivity is observed with 2//-cyclopenta(d)pyridazine and its 2-methyl and 2-phenyl analogs. Monochlorination of these compounds revealed the relative reactivities are 7,1 1,7 1 [78H(11)155]. If the cyclopentyl part is substituted with chlorine atoms, the 2-methyl compounds are transformed with A -chlorosuccinimide (NCS) into the 2-chloromethyl derivative (80JOC1695). In contrast to other perfluo-roazines, perfluoroalkylpyridazines, when fluorinated with cobalt trifluoride, lose nitrogen to give perfluorinated oleflns [8IJCS(P1)2059]. 

Reagents such as A-bromosuccinimide, A-chlorosuccinimide, ° A-bromocaprolactam, ° sulfuryl chloride, bromine,and <-butyl-hypochlorite have been used to prepare 5-haloisatins. Isatin with ICl gives S-iodoisatin. " Chlorination of 6-chloroisatin and 4-chloroisatingave 5,6- and 4,5-dichloroisatin, respectively. Various alkylisatins also undergo halogenation in the 5-position. ... 

Chlorination of quinoxalin-5-ol 1,4-dioxide with A-chlorosuccinimide in dichloromethane at room temperature yields 8-chloroquinoxalin-5-ol 1,4-dioxide. 

Using A-chlorosuccinimide (NCS), 4,5-disubstituted imidazoles afford 2-chloro substituted imidazoles. However, if other positions are available, chlorination goes preferentially at C-5 first, then C-4, and lastly, C-2. Selective chlorination (or halogenation in general) at the 2-position can be achieved via deprotonation using LDA, at the 2-position, followed by quenching with NCS or NBS (Scheme 65) <2003JME3463>. 

Compound 160 was chlorinated with A -chlorosuccinimide to give the oxaselenole derivative 161 (Equation 41). Similarly, compounds 162 were converted to oxaselenole derivatives 112 (Equation 42) <2001HAC317>. 

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