And ambident nucleophiles

The regiochemistry of the coupling products between aryl radicals and ambident nucleophiles was at the center of the recent work of Pierini et al. [116] (see Table 4). Changing the heteroatom of the nucleophile into a softer one by going down in the periodic table (from naphtholate to naphthylthiolate for instance) leads to an increase in heteroatom substitution C substitution increases when the nucleophile heteroatom is more electronegative or if the aryl moiety of the nucleophile is a more delocalized one. 

This equation, when applied to an ambident nucleophile with nucleophilic centers 1 and 2, becomes... 

The equation does not take into account such pertubation factors as steric effects, solvent effects, and ion-pair formation. These factors, however, may be neglected when experiments are carried out in the same solvent at the same temperature and concentration for an homogeneous set of substrates. So, for a given ambident nucleophile the rate ratio kj/kj will depend on A and B, which vary with (a) the attacked electrophilic center, (b) the solvent, and (c) the counterpart cationic species of the anion. The important point in this kind of study is to change only one parameter at a time. This simple rule has not always been followed, and little systematic work has been done in this field (12) stiH widely open after the discovery of the role played by single electron transfer mechanism in ambident reactivity (1689). 

The problem is more complicated when the ambident nucleophile. 2-aminothiazole, reacts with an ambident electrophilic center. Such an example is provided by the reaction between 2-amino-5-R-thiazole and ethoxycarbonyl isothiocyanate (144), which has been thoroughly studied by Nagano et al. (64, 78, 264) the various possibilities are summarized in Scheme 95. At 5°C, in ethyl acetate, the only observed products were 145a, 148. and 150. Product 148 must be heated to 180°C for 5 hr to give in low yield (25%) the thiazolo[3.2-a]-s-tnazine-2-thio-4-one (148a) (102). This establishes that attack 1-B is probably not possible at -5°C. When R = H the percentages of 145a. 148. and 150 are 29, 50, and 7%, respectively. These results show that ... 

Hydroxyl Group. Reactions of the phenohc hydroxyl group iaclude the formation of salts, esters, and ethers. The sodium salt of the hydroxyl group is alkylated readily by an alkyl hahde (WiUiamson ether synthesis). Normally, only alkylation of the hydroxyl is observed. However, phenolate ions are ambident nucleophiles and under certain conditions, ring alkylation can also occur. Proper choice of reaction conditions can produce essentially exclusive substitution. Polar solvents favor formation of the ether nonpolar solvents favor ring substitution. 

Molecules that possess more than one nucleophilic si are referred to as ambident nucleophiles. Sn2 reactioi involving these nucleophiles may lead to mixtures i products. For example, nucleophilic attack by nitrite c methyl bromide gives both nitromethane and methyl nitrit... 

The cyanide ion is an ambident nucleophile and isocyanides may be side products. If the preparation of isocyanides is desired, they can be made the main products by the use of silver or copper(I) cyanide (p. 459). Vinylic bromides can be converted to vinylic cyanides with CuCN, with KCN, a crown ether, and a... 

This means there are 42 entries that have the words AMBIDENT and NUCLEOPHILE somewhere in them in the titles, keywords, or index entries. We can now, if we wish, display any or all of them. But a particular entry might have these two words in unrelated contexts, for example, it might be a paper about ambident electrophiles, but which also has NUCLEOPHILE as an index term. We would presumably get fewer papers, but with a higher percentage of relevant ones, if we could ask for AMBIDENT NUCLEOPHILE, and in fact, the system does allow... 

If we ask for AMBIDENT NUCLEOPHILE without the (W), the system treats it as if we asked for AMBIDENT(W)NUCLEOPHILE, and gives the same answers. 

In a study of the attack of the ambident nucleophile ethanolamine on a series of phosphorylating agents (48) and related compounds it was observed that the proportion of O-phosphorylation increased as R and R varied in the series McaN, RO, R and as X varied in the series R2PO, CN, F, this last giving exclusive 0-phosphorylation. These results were... 

Another premise cannot be excluded and will be investigated eventually. As in the case of cyanide ion, isothiocyanate ion may be a precursor in the biosynthesis of some marine isothiocyanates. Like cyanide, thiocyanate ion is an ambident nucleophile. Specific incorporation of this ion by a carbocationic site... 

However, in our opinion, the rigorous assignment of products to covalent nitronic esters rather than to their structural isomers, which are true nitro compounds or ionic salts, is a more important and complex problem This problem involves difficulties, because ambident anions of nitro compounds (which are evident precursors of nitronates) have comparable O- and C-nucleophilicities and, therefore, the resulting substrates can belong to any of the above mentioned series. Incorrect structure assignments of derivatives of polynitro compounds prepared from tetranitromethane were made in former studies. In addition, the structures of nitronates assigned to some products in early studies, should not have been accepted without the use of modem spectral methods. 

The role of phosphoramidates and phosphazenes as 7V,0-ambident nucleophiles has been considered.79 Thus in the reaction of (EtO)3P=NCOPh with hydrogen chloride it appears that nitrogen rather than oxygen undergoes protonation ... 

Although oximes are ambident nucleophiles, a neat regioselectivity allows the formation of oxazolinones. The alpha effect, which is especially relevant for the substimtion of R2C=NO anions at a carbonyl carbon, may offer a good explanation for the Bac2/Bai2 sequence ((9-methoxycarbonylation and A-methylation... 

Hydroxylamine derivatives are ambident nucleophiles. For example, N-benzylhy-droxylamine functions as an N-nucleophile in the Ir-catalyzed allylic substitution, while N-Boc-hydroxylamine yields mixtures of the N- and O-substituted products in Ir- as well as Pd-catalyzed allylic substitutions. Accordingly, either O- or N,0-protected hydroxylamine derivatives need to be used as nucleophiles [63]. 

Concerning the mechanism of the rearrangement, it is proposed to involve the addition of the nucleophilic nitrogen of the 1,3-ambident nucleophiles to C-6 (see Section III,A,2,a). This covalent adduct is in equilibrium with the open-chain diamidino compound 83 (R = OCH3, SCH3). Cycliza-tion into 84, followed by a base-catalyzed fragmentation of the nitrogen-carbon bond at N-3 and expulsion of the thiomethyl or methoxy anion, yields the 2-amino-4(5)-phenylpyrimidines (Scheme III.47). 

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