During nucleophilic substitution

FIGURE 8 2 Hybrid orbital description of the bonding changes that take place at carbon during nucleophilic substitution by the Sn2 mechanism... 

In view of the known behaviour of pyrazines during nucleophilic substitution reactions, it comes as no surprise that anomalous reactions appear during nucleophilic substitution... 

Only rarely is the amino group itself anionized during nucleophilic substitution one instance is the reaction of sodamide with 2-aminopyridine to yield 2,6-dianJnopyridine (cf. structure 74 on p. 185). 

Common solvents. For hydrophilic amines such as 4-aminobutyric acid, distilled water is the preferred solvent. For hydrophobic amines such as 4-aminobenza-mide, a DMF water 50% v/v solution may be an option. In any case, usually 1 molar equivalent of NaHC03 is added in order to neutralize the HC1 released during nucleophilic substitution. Caution DMF is harmful and considered a potential carcinogen. Should be handled in a fume hood. 

During nucleophilic substitutions the hybridization at carbon changes from sp3 to sp2 for an electrophile R3CX this leads to widening of the angle RCR from 109° to 120° in the transition state (Sn2) or in the intermediate carbocation (SnI). In cyclic secondary or tertiary electrophiles this required angle widening can lead either to an increase or to a relaxation of strain (Scheme 4.22). 

Fig. 4. The reaction steps during nucleophilic substitution in the dilute gas phase. The upper route corresponds to backside displacement (the traditional SN2 mechanism) and the lower route is the frontside displacement mechanism. The latter is possible in weakly bonded RX+...

Displacement of hydrogen with nucleophiles is rare and is typified by the Chitschibabin reaction. The ease of displacement of substituents during nucleophilic substitution reactions varies, depending upon the substitution pattern in the particular system. 

There is some evidence that the influence of the ferrocene extends even to cations in the -position, so that retention during nucleophilic substitution is also found here [38, 39]. This chemistry has not been developed further, presumably because -functionalized ferrocenes are less easily accessible. 

It is well established that sulfur and oxygen anions behave in an opposite way with electrophilic centres during nucleophilic substitutions. The comparison of the reactivity of 1-octanthiol and 1-octanol with DMC (entries 3 and 4, Table 9) outlines the difference in chemoselectivity of RS and RO anions, due to their diverse hardness. Under all of the investigated conditions, alkoxides show a Bac2 reaction mechanism, differently from thiolates, which react via a B,2 type. 

The formation of rearranged products during nucleophilic substitution in a-bromo-ketones probably involves enolisation, followed by allylic (5n2 ) substitution. The ready conversion of4, 5i8-epoxy-3-ketones (45) into 2a-acetoxy-or 2a-hydroxy-4-en-3-ones is similarly rationalised.When the nucleophile is dimethyl sulphoxide, the resulting 2-oxysulphonium ion (46) breaks down with elimination of dimethyl sulphide to give the 4-ene-2,3-dione (47), or its A -enolic equivalent (48). 

A new development in the synthesis of polyfluoroarylacetylenes is the use of a trialkylsilyl protecting group, for example to prevent metallation at an acetylene terminus during nucleophilic substitution of perfluorobenzene (Scheme 47). The protecting groups are readily removed by methanol ic... 

Simpler cases of Wagner-Meerwein processes are also known. For example, alkyl migration during addition of HX to alkenes (Chapter 6, Scheme 6.19) has already been noted. Similarly, to the extent that the same carbocations are generated during nucleophilic substitution reactions, the same processes occur Indeed, almost identical rearrangments will be encountered again in Chapter 8 in the discussion of derivatives of alcohols as they are here with alkyl halides. 

Figure 20.13 Using silver nitrate solution to indicate the release of halide ions during nucleophilic substitution the white precipitate of silver chloride is yet to appear in the left-hand tube, showing that this substitution is the slowest of the three... 

Figure 20.76 The inversion of 2-bromooctane during nucleophilic substitution (sometimes referred to as a Walden inversion)...

Fig. 3. H-NMR spectrums recorded during nucleophilic substitution reaction (spectrum D pure compound 2 spectrum E, recorded after 2 h reaction spectrum F, pure compound 3).

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