Chloro function displacement

General procedures for the displacement of a chloro function from purines Some halide substituents on nitrogen heterocycles are difficult to substitute by means of nucleophilic aromatic substitution. In order to overcome the lack of reactivity at the C2 position of purines, Pd-mediated reactions are used for C-C and C-N bond formations (Scheme 12) [36, 91],... 

Friedel-Crafts acylation of 6-chlorooxindole 1861 (Figure 6.32) with chloro[2- C]acetyl chloride afforded the corresponding 5-(chloro[l- C]acetyl) derivative 22. which was reduced to give the 2-chloro[l- C]ethyl analog 88- Displacement of the 2-chloro function with amine 89 gave the antipsychotic [ " C]CP 88-058 1901. ... 

An alternate scheme for preparing these compounds starts with a prefabricated pyrimidone ring. Aldol condensation of that compound (95), which contains an eneamide function, with pyridine-3-aldehyde (80), gives the product 96. Catalytic hydrogenation gives the product of 1,4 reduction. The resulting pyrimidinedione, of course exists in the usual tautomeric keto (97a) and enol (97b) forms. Reaction with phosphorus oxyxchloride leads to the chloro derivative 98. Displacement with methoxide gives 99. Reaction of this last intermediate with the furylalkylamine derivative 92 leads to the H-2 blocker lupitidine (100) [22]. 

Nucleophilic processes that generate chloroindoles are largely confined to the displacements of oxy functions and Sandmeyer reactions of diazo-nium salts [81 H( 15)547]. A low yield of 2-chloroindole was obtained by a reaction sequence that involved treatment of oxindole with phosphoryl chloride, and then treatment of the Vilsmeier salt with sodium bicarbonate [66JOC2627 86H(24)2879]. It is, however, much better to prepare this compound from 2-lithioindole (92JOC2495). With phosphoryl chloride and dimethylformamide ethyl l-hydroxyindole-2-carboxylate failed to give the expected 3-formyl derivative. Instead there was a 50% yield of the 3-chloro derivative (84CPB3678). Diazonium salts have been used as precursors in... 

Terpyridine ligand 20, with appropriate functionalization at the 4 position (introduced by nucleophilic displacement of a 4 -chloro substituent) is the key building block used by Newkome and by Constable. The assembly of the beautiful dodecaruthenium macromolecule 24 carrying a 24 charge was an early highlight... 

Nucleophilic processes that introduce chlorine include displacement of diazonium functions, but these are not well known in the imidazoles because of the instability of many simple aminoimidazoles. In one instance the lack of success may have been a function of the high stability of 5-ethoxycarbonyl-4-diazoimidazole. Other 1-substituted 4-diazonium salts showed expected reactivity, and 1-substituted 5-aminoimidazoles formed sufficiently reactive diazonium salts to give good yields of the 5-chloro compounds [80JCS(P1)2310]. Most of the thrust in this reaction strategy has focused on the preparation of fluoroimidazoles (see B,2,d). 

Dener et al.28 also indicated a list of amine functionalities that fail to displace the 2-chloro group. In turn, Wu et al29 performed similar chemistry displacing the chloro group at the C2 position under milder conditions (lower temperature), but this methodology is restricted to more electron-deficient and more reactive quinazolines bearing further chloro groups at C6, C7, or C8. 

Polyphenylsilane, (PhSiH) , can be derivatized by free-radical hydrosilylation in the presence of a radical initiator. Alkenes, ketones and aldehydes react readily, to replace up to 93% of the Si-H bonds. This route can be employed to make polysilanes with hydrophilic groups, such as hydroxy, amino and carboxylic acid functions.43 Dialkylamino substituted polysilanes, made by the anionic polymerization of masked disilenes (see equation (17)), when treated with acetyl chloride give chloro-substituted poly silanes. The chlorine can then be displaced by other nucleophiles.27... 

These key intermediate is accessible from triacetyl-D-glucal 38 in a large-scale adaptable 5-step sequence in an overall yield of 30 % conversion of 38 into hexenoside 39 according to a known two-step procedure (55), tosylation to the chloro-tosylate 40, since the chloride ions formed during the reaction in situ displace the activated allylic tosyloxy function, and, finally, the consecutive reductive removal of tosyloxy- and chloro groups 40 -> 35 (56,57) ... 

Ring substituents of pyrazine A-oxides show increased reactivity, and substituents in the a-position to the A7-oxide function are more reactive than those in the /3-position. Thus, 2-chloropyrazine 1-oxide is converted into the 2-hydroxy-1-oxide on mild alkali treatment,398 but attempts to carry out a similar reaction with the 2-chIoro-4-oxide were not successful.412 Ammonolysis of the 2-chloro-4-oxide has been achieved, and nitrous acid treatment of the resulting 2-amino-4-oxide gives 2-hydroxypyrazine 4-oxide (Scheme 46). The chlorine atom of both isomeric 2-chloropyrazine A-oxides is readily displaced with sulfanilamide to give the corresponding sulfanilamidopyrazine A-oxides.413,414... 

The marked activation of the iV-oxide function on the chlorine atom of 2-chloropyrazine 4-oxide and 2-ehloro-3,6-dimethylpyrazine 4-oxide is also demonstrated by the milder conditions under which these compounds react with ammonia and amines compared with chloro-pyrazine and 2-chloro-3,6-dimethyl pyrazine, respectively. Although 2-chloropyrazine 4-oxide undergoes the expected displacement reaction with ammonia on heating at 115°-120° for 2.5 hours, reaction at 140° for 16 hours gives 2,3-diaminopyrazine, possibly as a result of an addition-elimination reaction on the initially formed 2-amino-pyrazine 4-oxide (Scheme 47).417... 

Reactive dyes typically contain the chlorotriazinyl group. The chloro substituent can be displaced by hydroxy functional groups from cellulosic fibres thereby incorporating the dye molecule into the fabric. Bright and lightfast colors are obtained by this approach. Reactive dyes for cotton generally contain a number of sulfonic groups to provide the water solubility which is required to apply the dyes from aqueous solutions. 

Vanadocene halide is another important analog that is transformed to various vanadocene derivatives. Vanadocene chloride is prepared from vanadium(III) chloride and thallium cyclopentadienide or vanadocene and hydrogen chloride. Vanadocene dihalide is similarly synthesized from vana-dium(IV) halide via nucleophilic substitution. " Displacement of the chloro group results in functionalization as shown in Scheme 15. 

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