Nucleophilic substitution reactivity/regioselectivity

Complexes of the type (ri -arene)Cr(CO)3 are very important from the viewpoint of selective organic synthesis involving aromatic substitution reactions since the tricar-bonylchromium moiety attached to the arene ring can modify its reactivity. Interesting stereo- and regioselective organic syntheses have been developed based on the specific properties of (ri -arene)Cr(CO)3 [32]. A typical example of nucleophilic substitution on the aromatic ring by a carbanion is shown in eq (12). 

Reactions of benzodiazines show no exceptional features compared with the simple diazines. Reactivity towards electrophiles is less than in quinoline and isoquinoline. If S Ar reactions take place, they lead to substitution of the benzene ring. As a rule, nucleophilic substitution of benzodiazines occur in the diazine ring, particularly if substituted by halogen. The quinazoline system displays C-4 regioselectivity, e.g. in the reactions of 2,4-dichloroquinazoline with amines or alcohols ... 

Although nucleophilic reactions of the smallest [n]metacyclophane 4a (Structures 1) was not reported, unusual reactivity of its halogen-substituted derivatives 4b-e (Scheme 9, Structures 23) toward nucleophiles was reported by Bickelhaupt [66, 74]. Treatment of chlorocyclophanes 4b and 4e with sodium alkoxide gave nucleophilic substitution products 4f and 4g (Structures 23), respectively, through a S yAr mechanism [74b]. The regioselective substitution at C-11 is explained in terms of (i) greater stability of the Meisenheimer complex... 

Tetrafluoropyrazine Reactions of tetrafluoropyrazine with nucleophiles occur readily (Fig. 8.16) and, of course, there are no issues regarding regioselectivity of the first nucleophilic substitution process due to the symmetry of this system. The reduced reactivity of tetrafluoropyrazine compared to the other perfluorinated diazines reflects the absence of highly activated sites para to ring nitrogen. 

A common problem in the manufacture of fine chemicals is that a substrate may have more than one reactive site. A well known, but intractable, problem is the nitration of monosubstituted benzenes, which always leads to a mixture of isomers. Reactions which involve nucleophilic substitution are more amenable to control of regioselectivity by choice of solvent. An excellent review on the reactivity of ambident anions is available, in which this subject is treated [17]. An instructive example is the alkylation of phenol with allyl chloride [18] (equation 12.10). Table 12.13 shows how the properties of O- and C-alkylation are affected by solvent. 

A more modern approach for the direct introduction of a carbon side-chain into the pteridine nucleus has been developed by homolytic nucleophilic substitution reactions , especially using acyl radicals -i as well as alkyl radicals as reactive species. These reactions, however, take place regioselectively with 6,7-unsubstituted pteridine derivatives at the most electron-deficient 7-position leading to the unnatural isomers. Direction of the incoming nucleophile towards the C-6 atom can only be achieved in the presence of a 7-substituent " . A reasonable "protecting" group for C-7 has been the alkylmercapto and thione function, since it was found that the difficulties encountered with the Raney-nickel desulfurization reaction " in the pteridine series could be overcome using Raney-cobalt and copper-aluminum alloy, respectively . 

In Brown s classification a diazonium ion is a reagent of very low reactivity and correspondingly high substrate selectivity and regioselectivity. This follows from the fact that benzenediazonium salts do not normally react with weakly nucleophilic benzene derivatives such as toluene. More reactive heteroaromatic diazonium ions such as substituted imidazole-2-diazonium ions will even react with benzene (see Sec. 12.5). 

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