Ambident electrophiles nucleophiles

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 ... 

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

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... 

The 1,2,4-triazine ring is an ambident electrophile, and reacts with enamine-type nucleophiles. For example, addition of enamine 78 to a solution of triazine 77 in acetic anhydride furnished the pyrrolotriazine 31 (Equation 24) <2003TL2421>. 

The presence of two electrophilic reaction centers in the molecule of o -unsaturated carbonyls is responsible for their ability to participate in the synthesis of heterocycles. Such compounds can react as ambident electrophiles owing to delocalization of electron density in a C=C-C=0 system. The addition of nucleophiles to these molecules can proceed in one of two main directions—via attack of the carbonyl group (1,2-addition) or involving the / -carbon (1,4-addition). 

The properties of dimethyl carbonate, (MeO)2CO, as an ambident electrophile have been investigated by analysis of the products of its reaction with various nucleophiles having different hard-soft character. Results were in good agreement with the Hard-Soft Acid-Base theory, hard nucleophiles attacking the hard C=0 group and soft nucleophiles the soft Me group (Scheme ll).37... 

Apart from the above two major general reaction pathways, there are some further possibilities for instance, [bis(trifluoroacetoxy)iodo]benzene reacts as an ambident electrophile and is attacked by hard nucleophiles at its carbonyl carbon, whereas iodylarenes may react similarly from carbon rather than iodine. Alkynyl iodonium salts are actually tetraphilic electrophiles, whereas iodosylbenzene reacts also as a nucleophile from oxygen. Diaryl iodonium salts serve as arylating reagents, mostly homolytically other iodonium salts transfer groups such as perfluoroalkyl, vinyl, alkynyl or cyano to several nucleophiles in various ways. 

Though exhibiting both electrophilic and nucleophilic reactivity, ketoenamines usually react as ambident nucleophiles at their nitrogen or (and) Cp atom. Ambident electrophiles are therefore suitable partners for cyclization yielding heterocycles. 

A nice example of the solvent-dependent dual reactivity of an electrophilic crypto-cationic species has been given by Hiinig et al. [663]. Ambident electrophilic a-enones react with nucleophiles such as the anion of the benzaldehyde O-(trimethylsilyl)-cyanohydrin (Nu ) in diethyl ether exclusively by 1,4-addition. In tetrahydrofuran (THF) or 1,2-dimethoxyethane (DME), the 1,2-adduct is formed predominantly on the addition of HMPT or [12]crown-4 it is formed exclusively cf. Eq. (5-133). 

Mcthoxycarbenium ion is an ambident electrophile reaction can occur at either C or O. Nucleophilic attack at the C atom results in mcthoxymetbylation. Displacement of formaldehyde results in mcthylation of the nucleophile. The latter reaction is prevalent with aromatics. Thus the reaction of the reagent with benzene gives toluene in high yield. 

The main feature of these compounds is their tautomerism and resultant ambident electrophilic reactivity. Their reactivity is therefore highly dependent upon the electron distribution within the ring. Electrophilic attack occurs P to either the ring nitrogen or sulfur, whereas nucleophilic attack tends to take place at the a-position, normally C-2. Nucleophiles can also deprotonate the heterocycle, acting as bases. 

Freitas and O Hair133 studied the gas-phase reactivity of aniline and other nucleophiles toward the methoxymethyl cation, CH3 — 0+=CH2, an ambident electrophile, using flowing afterglow mass spectrometry. For aniline, two reaction channels were observed addition followed by elimination of methanol with concomitant [M + CH]+ ion formation and adduct formation, viz. [M + CH3OCH2]+. 

With this very simple, if possibly not quite accurate, explanation of a puzzling series of observations, we leave the subject of ambident nucleophilicity, and turn to the much smaller subject of ambident electrophilicity. 

A complication arises in that the nucleophile now has a choice it can add in a conjugate fashion, or it can add to the electron-withdrawing group directly. Section 9.6, Ambident Electrophiles, discusses this problem in depth. Examples of these sinks are ... 

There are molecules that have two-electron deficient centers capable to react with nucleophiles. Such molecules are called ambident electrophiles. The reactivity profile is susceptible to the same kind of analysis as the one we have had above for the reaction of ambident nucleophiles with electrophiles. In the reaction of an electrophile with a nucleophile, it is the LUMO of the electrophile that interacts with the HOMO of the nucleophile. As such, the higher the HOMO and/or the lower the LUMO to reduce energy gap between the two, the faster will be the reaction. Alternatively, the better the match of the HOMO and LUMO coefficients, the more effective will be the reaction. 

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