Nucleophilicity, ambident nucleophiles

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). 

This section is organized according to the electrophilic center presented to the nucleophilic nitrogen of the active species. This organization allow s a consistent treatment of the reactivity. However, a small drawback arises when ambident electrophilic centers are considered, and these cases are treated as if the more reactive center were known, which is not always the case. 

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 ... 

Nevertheless, the puzzling fact to be explained is that the harder ring nitrogen prefers the softer electrophilic center and that this preference is more pronounced than the one observed for the amino nitrogen. Much remains to be done to explain ambident heterocyclic reactivity it was shown recently by comparison between Photoelectrons Spectroscopy and kinetic data that not only the frontier densities but also the relative symmetries of nucleophilic occupied orbitals and electrophilic unoccupied orbitals must be taken into consideration (308). 

Ambident reactivity of the same nucleophilic species toward different nitrosation electrophilic centers. 

Since the exocyclic sulfur is more reactive in the ambident anion than in A-4-thiazoIine-2-thione. greater nucleophilic reactivity is to be expected. Thus a large variety of thioethers were prepared in good yields starting from alkylhalides (e.g.. Scheme 38 (54, 91, 111, 166-179). lactones (54, 160), aryl halides (54, 152. 180, 181), acyl chlorides (54. 149, 182-184). halothiazoles (54, 185-190), a-haloesters (149. 152. 177. 191-194), cyanuric chloride (151). fV.N-dimethylthiocarbamoyl chloride (151, 152. 195. 196), /3-chloroethyl ester of acrylic acid (197), (3-dimethylaminoethyl chloride (152). l,4-dichloro-2-butyne (152), 1,4-dichloro-2-butene (152), and 2-chloro-propionitrile (152). A general... 

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. 

The pattern of reactivity is similar to that discussed for the azolinones in Sections 4.02.1.1.4 and 4.02.3.7.1. A difference is the greater nucleophilicity of sulfur, and thus more reaction of the ambident anion with electrophiles occurs at sulfur. 

A mechanism of this type permits substitution of certain aromatic and ahphatic nitro compounds by a variety of nucleophiles. These reactions were discovered as the result of efforts to explain the mechanistic basis for high-yield carbon alkylation of the 2-nitropropane anion by p-nitrobenzyl chloride. p-Nitrobenzyl bromide and iodide and benzyl halides that do not contain a nitro substituent give mainly the unstable oxygen alkylation product with this ambident anion ... 

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... 

Other possible ambident nucleophiles include cyanii anion (CN ), methyl sulfinate anion (CH3SO2 ), ar acetone enolate (CH3COCH2 ). Identify the most electro rich atom(s) in each anion (based on charges alone), ar indicate the major product that should result from an S, reaction with methyl bromide at this atom(s). 

Can the ambident nucleophilicity of any of these anioi be explained solely on electrostatic grounds Solely ( orbital overlap grounds Explain your reasoning. 

Palladium(0)-catalyzed allylation of ambident nucleophilic aromatic heterocycles 96AHC(66)73. 

Since the cyanide anion is an ambident nucleophile, isonitriles R—NC may be obtained as by-products. The reaction pathway to either nitrile or isonitrile can be controlled by proper choice of the counter cation for the cyanide anion. 

Amberlyst resin 538 Amberlyst-15 (H+) 762 f. ambident electrophile 456, 478 ambident nucleophile 78 amides... 

In a method for propargylating an alkyl halide without allylic rearrangement, the halide is treated with lithio-l-trimethylsilylpropyne (122) which is a lithium compound protected by an SiMca group.Attack by the ambident nucleophile... 

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... 

As so far described, online searching is faster then searching the printed CA, but gives us essentially the same information. The scope of the online method is much greater than that, for it allows us to combine words, in a number of ways. One such way is by the use of the terms AND, NOT, and OR. If we search AMBIDENT AND NUCLEOPHILE, we will get something like this... 

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. 

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