Bases and Nucleophiles

Bases always contain a lone pair of electrons which can form a bond to a proton. Most, but not all, bases have a negative charge. We have seen an example of a reaction of bases with halogenoalkanes to give alkenes in the last chapter, and others will follow in this chapter. 

2 for OH - to zero for H20, in line with base strengths, but nucleophiles such as 1 and Br are strongly nucleophilic even though they are very weak bases. A likely explanation is that small ions such as OH- and F are highly solvated in water, whereas bigger ions such as I- and Br are less solvated. The solvation energy is partially lost as the covalent bond forms in the transition state for the SN2 reaction, which retards the rate more for the small nucleophiles. 

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Potassium Hydride. Potassium hydride [7693-26-7] KH, made from reaction of molten potassium metal with hydrogen at ca 200°C, is suppHed in an oil dispersion. Pressure Chemical Company (U.S.) is a principal suppHer. KH is much more effective than NaH or LiH for enolization reactions (63,64). Use of KH as a base and nucleophile has been reviewed (65). 

Distinction between General Base and Nucleophilic Catalysis... 

The technique has also been applied to the distinction between general base and nucleophilic catalysis. ... 

Ethers are unreactive to many reagents used in organic chemistry, a property that accounts for their wide use as reaction solvents. Halogens, dilute acids, bases, and nucleophiles have no effect on most ethers. In fact, ethers undergo only one reaction of general use—they are cleaved by strong acids. Aqueous HBr and HI both work well, but HCl does not cleave ethers. 

Aryl hydrazide linker 38 stable to both acid and base was utilized in SPPS [46], Treatment of the resin with a copper(II) catalyst in the presence of a base and nucleophile gave the corresponding acid, amide, or ester (Scheme 13). 

Catalysis, enzymatic, physical organic model systems and the problem of, 11,1 Catalysis, general base and nucleophilic, of ester hydrolysis and related reactions, 5,237 Catalysis, micellar, in organic reactions kinetic and mechanistic implications, 8,271 Catalysis, phase-transfer by quaternary ammonium salts, 15,267 Catalytic antibodies, 31,249... 

General base and nucleophilic catalysis of ester hydrolysis and related reactions, 5, 237... 

When 3-(4-chlorofurazanyl-3-Ar(0)AT-azoxy)-4-nitrofurazan 218 reacts with weak bases and nucleophiles, selective attack on the carbon atom bonded to the nitro group occurs, but no products formed by substitution of the chlorine was observed (Equation 43) <2003CHE1357>. 

Following the disclosure of the outstanding catalytic ability of imidazole compared to other bases, the catalysis of the POCL reaction by imidazole was studied in more detail [163], and it was concluded that the POCL reaction mechanism included the concurrent catalysis by two imidazole molecules, by what was described as general-base and nucleophilic pathways, respectively. The mechanism for this was suggested to be a base catalysis of imidazole catalysis by imidazole itself as previously reported for imidazole-catalyzed reaction of esters [164, 165], Despite this, it was not until the introduction [151] of 1,1 -oxalyldiimidazole (ODI) as a chemiluminescence reagent, and the postulation of its intermediate appearance in the imidazole-catalysed POCL reaction, that the... 

A double mutant (acid/base and nucleophile) Abg E71A E358G was developed58 which efficiently catalyzes thioglycoside formation from a glycosyl fluoridine donor (69) with inverted anomeric stereochemistry. This represents a significant improvement, as glycosyl fluoride donors are much more accessible (Fig. 29). 

Primary vinyl iodonium compounds (1, R3 = H) are readily prepared as stable salts, but secondary analogs (1, R3 = alkyl) cannot be isolated without the presence of electron-accepting moieties. Cyclopent-l-enyl iodonium salt is very stable and poorly reactive toward bases and nucleophiles, while cyclohept-l-enyl... 

Piperazine (13) is a base and nucleophile employed (6% in dimethylformamide) in solid-phase synthesis for removal of fluorenylmethyl-based protectors. The reaction is slower (three times) than with piperidine, but it leads to minimal aspartimide or piperazide formation. 

Aminoethyl)piperidine (16) is a base and nucleophile employed for removal of fluorenylmethyl-based protectors during synthesis in solution. The adduct formed with the released moiety can be separated from the peptide ester by extraction into a pH 7.4 phosphate buffer (see Section 7.11). 

Gaseous carbonium ions from the decay of tritiated molecules, 8, 79 General base and nucleophilic catalysis of ester hydrolysis and related reactions, 5, The Gomberg Century Free Radicals 1900-2000, 36, 1 Gomberg and the Nobel Prize, 36, 59... 

Acetals and ketals are very important protecting groups in solution-phase synthesis, but only a few constructs have been used as linkers in solid-phase synthesis (Tab. 3.3). The THP-linker (22) (tetrahydropyran) was introduced by Ellman [54] in order to provide a linker allowing the protection of alcohols, phenols and nitrogen functionalities in the presence of pyridinium toluene sulfonate, and the resulting structures are stable towards strong bases and nucleophiles. Other acetal-linkers have also been used for the attachment of alcohols [55, 56]. Formation of diastereomers caused by the chirality of these linkers is certainly a drawback. Other ketal tinkers tike... 

The EPR spectra of electrolytically produced anion radicals of Q -aminoanthraquin-ones were measured in DME and DMSO. The isotropic hyperfine coupling constants were assigned by comparison with the EPS spectra of dihydroxy-substituted antraquinones and molecular-orbital calculations. Isomerically pure phenylcarbene anion (PhCH ) has been generated in the gas phase by dissociative electron ionization of phenyldiazirine. PhCH has strong base and nucleophilic character. It abstracts an S atom from and OCS, an N atom from N2O, and an H atom from... 

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