Nucleophilic Substitution of Chlorine

In the previous sections it has been shown that all four stereoisomers of the chlorinated dihydroxy ester 5a can be synthesized in an enantiopure form on a preparative scale. In order to extend the applicability of these compounds a nucleophilic substitution of chlorine was sought. 

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Table 2. Yield of nucleophilic substitution of chlorine in [FeCp(C6H5Cl)]+ by amino groups using amines at 20 °C...

A phenylsulphinyl group has been found to promote the nucleophilic substitutions of chlorine at positions ortho and para to the aromatic ring (equation 313)609. 

In many cases, the yields of these products are high. However, the use of /V-silylated triazoles as nucleophiles or the use of cyclic nitroso acetals (475) substituted at the C-3 atom leads to a noticeable decrease in the yield of the oximes. Therefore, steric hindrance in nitroso acetals and a decrease in nucleophilicity of A-centered nucleophiles result in an increase in the contribution of side reactions. It should be emphasized that C -nucleophiles, such as anions of nitro compounds, are not involved in coupling reactions with cyclic nitroso acetals (475). However, the products, which formally correspond to the C,C-coupling mechanism, can be prepared by the nucleophilic substitution of chlorine in compound (476 d) by a Sa/2 mechanism (Scheme 3.254, product (483c), the yield was 79%). 

Chlordane is subject to hydrolysis via the nucleophilic substitution of chlorine by hydroxyl ions to yield 2,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4,7-methano-l//-indene which is resistant to hydrolysis (Kollig, 1993). The hydrolysis half-life at pH 7 and 25 °C was estimated to be >197,000 yr (Ellington et ah, 1988). 

Nucleophilic substitution of chlorine in 2,4-dinitrochlorobenzene by diethylamino group from triethylamine (Scheme 4.18) is a rare example when both the formed opposite-charged ion radicals exist together in the bulk solution for a long time. 

Neighboring group participation effects appear to play a crucial role in the nucleophilic substitution of chlorine in Michael adducts of 1-R, 2-R, 3-X. Thus, this substitution proceeds very easily in any of the adducts formed with an electron rich nitrogen, sulfur and oxygen Michael donor. For the adducts of nitrogen nucleophiles, the facile substitution of the chlorine has been suggested to occur via formation of intermediate aziridinium ions 103 [8] (Scheme 32), and this postulate was later supported by isolation of azaspiropentane derivatives under appropriate conditions in several reactions (see Sect. 3.2.2) [11b, 53,56]. It is most likely that alkylthio substituents in adducts of type 85 participate in the same way to first form spirocyclopropane-annelated thiiranium ion intermediates which are subsequently opened by attack of the incoming nucleophile. 

Scheme 32. Possible aziridinium ion intermediate 103 in the nucleophilic substitution of chlorine in Michael adducts of type 91 [8]...

Scheme 33. Nucleophilic substitution of chlorine in chloroamines 91 in methanol [11b]...

Scheme 35. Preparation of diaminoacid derivatives 106 via nucleophilic substitution of chlorine in )8-amino-a-chloro esters 91 [11,57]...

At last, upon the attempted nucleophilic substitution of chlorine in the Michael adduct 160c with cyanide an interesting rearrangement was observed which gave the 2-(r-cyanocyclopropyl)-2-(o-aminophenylthio)acetate 176, ap-... 

While some phenol is produced by the nucleophilic substitution of chlorine in chlorobenzene by the hydroxyl group (structure 17.17), most is produced by the acidic decomposition of cumene hydroperoxide (structure 17.18) that also gives acetone along with the phenol. Some of the new processes for synthesizing phenol are the dehydrogenation of cyclohexanol, the decarboxylation of benzoic acid, and the hydrogen peroxide hydroxylation of benzene. 

Nucleophilic substitution of chlorine, sulfonic acid, or amino groups by aromatic amines is a common process for producing triaminotriarylmethane dyes. Spirit blue (23) can be formed from the trichlorotriphenylmethyl cation (21) [6,7] and from pararosaniline (22) [8,9] by reaction with aniline. 

These compounds can condense and cyclize with resorcinol or substituted 3-aminophenols. Nucleophilic substitution of chlorine by amines leads to xanthene dyes which contain a sulfonic acid group [10] or hydrogen [11] instead of the carboxyl group. 

Medical grade PVC sheets and tubes were surface modified by nucleophilic substitution of chlorine atoms by photoactive diethyl dithiocarbamate in the presence of a suitable phase transfer catalyst. The modified surface was crosslinked by UV light to create a barrier for the diffusion of plasticiser. The effect of concentration of phase transfer catalyst and diethyl dithiocarbamate, time of reaction and irradiation dose on the extent of plasticiser migration was examined. 26 refs. 

Plasticised PVC sheets were surface modified by nucleophilic substitution of chlorine by azide in aqueous media under phase transfer conditions. The azidated PVC surface was then irradiated by UV light to crosslink the surface. It was found that considerable reduction in the migration of the plasticiser di-(2-ethylhexyl phthalate) could be achieved by this technique, depending on the extent of azidation of the PVC surface and the irradiation dose. After surface modification, there was around 30% reduction in the stress-strain properties of the PVC sheets but these values were still well above the minimum prescribed for PVC used in biomedical applications. 19 refs. 

Nucleophilic substitution of chlorine is a key feature of a synthetic approach to a series of indole-6-carboxylic acids. For example, conversion of the starting nitrobenzene 392 using an SnAc reaction followed by reductive cyclization into the indole 393 was concluded by treatment with base to afford the final product 394 (Scheme 46) <2004SL883>. 

The nucleophilic substitution of chlorine in aromatic sulfur(II) and sulfur(IV) derivatives proceeds under lower temperature (- 25 C + 5 C). Apparently, in these reactions, a stoichiometric quantity of tris(dimcthylamino)sulfonium difluorotrimethylsilicate should be used, e.g. for formation of 33 and 34." ... 

Nucleophiles Nu attack the N-Cl bond ((371) and (378)), formally an electrophilic or nucleophilic substitution of chlorine. In the reaction of electrophiles E+ with chloramine NH2CI, a nitrogen bound proton is substituted. This results in the transfer of the NHCC to E+. 

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