Hydroxide ion and other O-nucleophiles

Imidazoles and benzimidazoles (203) react with acid chloride and alkali to give compounds of type (205), but these are reactions of the cation (204). 1,2,4-Triazoles and tetrazoles similarly undergo ring opening. 

Isoxazoles are also rather stable to nucleophilic attack by OH at carbon. For reactions with base at a ring hydrogen atom, leading, for example, to ring opening isoxazoles, see Section 3.4.1.8.1. 

Oxazoles give acylamino ketone (206) by acid-catalyzed ring scission, although they are somewhat more stable than furans. The oxazole ring is also moderately stable to alkali (74AHC(I7)99) as expected, reaction with hydroxide ions is facilitated by electron-withdrawing substituents and fused benzene rings. 

Oxadiazoles are easily cleaved. 2,5-Dialkyl-1,3,4-oxadiazoles (207) in aqueous solution with acid or base give hydrazides (if suitable substituents are present, further reaction can occur see Section 3.4.3.5.1). 3-Methyl-1,2,4-oxadiazole (208) is easily hydrolyzed to acetamidoxime (61CI(L)292). 

UV spectroscopy has been used to clarify the strong interactions of 1,2,5-thiadiazole dioxides with protic solvents. Based on shifts in the maximum from 328 nm to 267 nm, as well as a doubling in the extinction coefficient, it is likely that the adduct (213) is formed in alcoholic media (93JP0341). 

---

Hydroxide ion and other O-nucleophiles Amines and amide ions S-Nucleophiles Halide ions Carbanions... 

As discussed in Sections 5.1-5.3, arenediazonium ions are Lewis acids in which the (3-nitrogen forms the center of electrophilic character. This was demonstrated by the addition of hydroxide ions and water molecules. Other nucleophiles can also be added and, in principle, these reactions display the same mechanistic characteristics as those with OH and H20. According to the nature of the atom of the nucleophile that provides the lone pair of electrons, O-, S-, Se-, N-, P-, or C-coupling can occur. With N- and C-coupling, important and large groups of compounds are formed, namely azo compounds (mainly important as azo dyes) and triazenes, respectively. These compounds will be discussed in Chapters 12 and 13, respectively. 

The reactivity of hydroxide ion (and that of other oxyanions) is interpreted in terms of two unifying principles (a) the redox potential of the YO /YO- (Y = H, R, HO, RO, and O) couple (in a specific reaction) is controlled by the solvation energy of the YO anion and the bond energy of the R-OY product (RX - - YO R-OY - - X ), and (b) the nucleophilic displacement and addition reactions of YO occur via an inner-sphere single-electron shift. The electron is the ultimate base and one-electron reductant which, upon introduction into a solvent, is transiently solvated before it is leveled (reacts) to give the conjugate base (anion reductant) of the solvent. Thus, in water the hydrated electron... 

In the light of recent work of Clark-Lewis on the condensation of alloxan with o-aminodimethylaminobenzene28-30 and with N-substituted diaminobenzenes (see Section II,A), other workers have reinvestigated related reactions and reformulated the products as spiro-quinoxaline derivatives. 1,3,10-Trialkylflavinium salts (e.g., 235) with nucleophiles, e.g., hydroxide ion, ammonia, or borohydride, yield the spiro-imidazolidinequinoxaline derivatives 236, 237, and 238.238... 

Hence the larger the n value, the stronger the nucleophile, and the smaller the [nucl]50o/o. As already pointed out earlier, the [nucl]50o/o values given in Table 2 show that in uncontaminated freshwaters, hydrolysis is by far the most important nucleophilic substitution reaction. Furthermore, since the hydrolysis of a carbon-halogen bond is generally not catalyzed by acids, one can assume that the hydrolysis rate of aliphatic halides will be independent of pH at typical ambient conditions (i.e., pH < 10). In this context it is also important to note that no catalysis of the hydrolysis of alkyl halides by solid surfaces has been observed (El-Amamy and Mill, 1984 Haag and Mill, 1988). In salty or contaminated waters, reactions of organic chemicals with nucleophiles other than water or j hydroxide ion may be important. Zafiriou (1975), for example, has demonstrated j that in seawater ([Cl ] 0.5 M), a major sink for naturally produced methyl j iodide is transformation to methyl chloride j... 

Figure 5 Working model for the initial catalytic complex of substrate with the dizinc center of phospho-triesterase. One zinc ion polarizes and activates the substrate, and nucleophilic attack of the bridging hydroxide is facilitated by the non-coordinated O atom of the Asp301 ligand to the other zinc ion.

---