Nucleophilic displacement, of leaving groups

The 2-alkyl anion derived from 2,5-dimethylthiadiazole (53) and sodium hydride adds to the annular carbon of (53) to give (54) <89CZ217>. Examples of nucleophilic displacement of leaving groups from the 2- and 5-positions of thiadiazoles are discussed in Section 4.10.8. 

The imidazo[l,5-a]pyridine ring system has been successfully functionalized with various electrophilic reagents, metalated, and reduced in one case. No nucleophilic displacements of leaving groups have been reported on appropriate derivatives. 

Nucleophilic displacement of leaving groups can also be carried out in suitable cases, for example, of the 4-methylthio in 3-cyano-2-pyrones. ... 

In addition to the nucleophilic substitution of hydride atom from quinolines and isoquinolines, a reaction of high value for introduction of variety of substituents is the nucleophilic displacement of leaving groups on the heterocycle. As an example, 4-chloro-8-trifluoromethylquinoline reacts in a nucleophilic displacement of chlorine atom with methyl anthranilate, to provide the precursor of NS AID antihacterial flocatfenine. ... 

Alkali metal (K, Na) [ CJcyanides have been extensively employed in the formation of alkyl [ CJnitriles via nucleophilic displacement of leaving groups such as primary halides, sulfonates and trialkylammonium salts in examples too numerous to mention. In special cases (e.g., 1) other leaving groups have been used, such as benzotriazol-l-yl. The most important considerations in the choice of leaving group are often the ease of substrate preparation and the compatibility of the displacement reaction with substrate ancillary functional groups. 

Nucleophilic substitution of leaving groups is probably the most important area in pyrimidine reactivity and, in particular, the differential reactivity of C-2 and C-4 is the most investigated topic. The displacement of 2- and 4-sulfide and sulfone groups is referred to in the synthesis section. The selective hydrolysis of 4-amino-2-chloropyrimidines under acidic conditions has been studied in great detail by a process research group <06OPRD921>. 

Studies of gas-phase S"n2 reactions at sp carbon have been made by Fourier transform ion cyclotron resonance mass spectrometry (FTlCRMS) and complemented by both semiempirical and ab initio MO calculations. The particular processes of interest involved intramolecular reactions in which neutral nucleophiles displace neutral leaving groups within cationic substrates, e.g. A-(2-piperidinoethyl)-2,4,6-triphenylpyridinium cation (59), in which the piperidino moiety is the nucleophile and 2,4,6-triphenylpyridine (60) is the leaving group. No evidence has been obtained for any intermolecular gas-phase 5) 2 reaction involving a pyridine moiety as a leaving group. The quantum mechanical treatments account for the intramolecular preference. 

Carbocationic intermediates. In a second mechanism of nucleophilic displacement the leaving group departs (often in a protonated form) before the entering nucleophile reacts. 

Nearly all of the cyclization reactions that we have discussed have been intramolecular Sn2 reactions where one end of the molecule acted as the nucleophile displacing the leaving group on the other... 

The chemistry of these very electron-deficient rings mostly concerns nucleophilic attack and displacement of leaving groups such as Cl by nucleophiles such as alcohols and amines. To introduce this subject we need to take one heterocyclic synthesis at this point, though these are properly the subject of the next chapter. The compound maleic hydrazide has been known for some time because it is easily formed when hydrazine is acylated twice by maleic anhydride. 

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