Substitution, nucleophilic chlorine

The N-oxides readily undergo nucleophilic addition followed by elimination, which forms the basis of several useful syntheses of 2-substituted pyridines. Chlorination of (13) with POCl to give 2-chloropyridine (17) is a good example (eq. 4) some chlorination may occur also at C-4 (11). 

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%). 

Sulfur atom as internal nucleophile. In this area, it has been shown that the reaction of 8-bromo-l,3-dimethyl-7-(2,3-epithiopropyl)xanthine 147 with a range of aliphatic and aromatic amines generates efficiently 2-amino-substituted 2,3-dihydro-thiazolo[2,3-/]xanthine derivatives 148. The process involves a sequential amine-induced thiirane ring opening followed by thiolate z/MYi-substitution of chlorine atom (Equation 66) <1994PCJ647>. 

The same phenomenon, i.e. that the secondary a-deuterium KIE is determined by the changes in only the shorter reacting bond in the SN2 transition state rather than by the nucleophile-leaving group distance, has been found in a completely different reaction system. Matsson, Westaway and co-workers (Matsson et al., 1996) used ku/k14 carbon incoming nucleophile, chlorine leaving group (Hill and Fry, 1962), and ku/ku a-carbon (Fry, 1970) KIEs to model the transition states for a series of SN2 reactions between p-substituted benzyl chlorides and labelled cyanide ion (reaction (17)). 

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. 

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. 

Chlorotetrolic esters are small, highly functionalized, reactive molecules of particular interest is the possibility of using them as reagents for chemical modification of biological macromolecules. Different protein nucleophiles react under mild conditions with methyl 4-chloro-2-butynoate by addition across the triple bond and/or substitution of chlorine while the triple bond and the ester group are involved in the reaction of chlorotetrolic... 

Dinitration of p-chloro(trifluoromethyl)benzene will take place at the ring positions ortho to the chlorine. Compound A is 2-chloro-5-(trifluoromethyl)-l,3-dinitrobenzene. Trifluralin is formed by nucleophilic aromatic substitution of chlorine by dipropylamine. Trifluralin is N, A-dipropyl-4-(trifluoromethyl)-2,6-dinitroaniline. 

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. 

Much attention was paid in CHEC-II(1996) to nucleophilic substitution in chlorinated cyclopenta- and cyclohepta-1,2,3-dithiazoles <1996CHEC-II(4)409>. 

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