Nucleophiles weakly basic

The high acidity of superacids makes them extremely effective pro-tonating agents and catalysts. They also can activate a wide variety of extremely weakly basic compounds (nucleophiles) that previously could not be considered reactive in any practical way. Superacids such as fluoroantimonic or magic acid are capable of protonating not only TT-donor systems (aromatics, olefins, and acetylenes) but also what are called (T-donors, such as saturated hydrocarbons, including methane (CH4), the simplest parent saturated hydrocarbon. 

Glycosidic thiol groups can be introduced into glycosyl bromides by successive reactions with thiourea and aqueous sodium disulfite (D. Horton, 1963 M. Cemy, 1961, 1963). Such thiols are excellent nucleophiles in weakly basic media and add to electrophilic double bonds, e.g., of maleic esters, to give Michael adducts in high yields. Several chiral amphiphiles have thus been prepared without any need for chromatography (J.-H. Fuhrhop, 1986 A). 

A second factor that can tip the balance m favor of substitution is weak basicity of the nucleophile Nucleophiles that are less basic than hydroxide react with both pri mary and secondary alkyl halides to give the product of nucleophilic substitution m high yield To illustrate cyanide ion is much less basic than hydroxide and reacts with 2 chlorooctane to give the corresponding alkyl cyanide as the major product... 

Benzylic halides that are secondary resemble secondary alkyl halides in that they undergo substitution only when the nucleophile is weakly basic If the nucleophile is a strong base such as sodium ethoxide elimination by the E2 mechanism is faster than substitution... 

The structural features especially the very polar nature of the carbonyl group point clearly to the kind of chemistry we will see for aldehydes and ketones in this chapter The partially positive carbon of C=0 has carbocation character and is electrophilic The planar arrangement of its bonds make this carbon relatively uncrowded and susceptible to attack by nucleophiles Oxygen is partially negative and weakly basic... 

Conjugate addition is most often observed when the nucleophile (Y ) is weakly basic The nucleophiles m the two examples that follow are C=N and C6H5CH2S respectively Both are much weaker bases than acetylide ion which was the nucleophile used m the example illustrating direct addition... 

P carbon atom of an a 3 unsatu rated carbonyl compound is elec trophilic nucleophiles especially weakly basic ones yield the prod ucts of conjugate addition to a 3 unsaturated aldehydes and ketones... 

Replacement of iodine in (perfluoroalkyl)ethyl iodides predominates over the usual conversion to olefins when the reagent is very nucleophilic and weakly basic Soft nucleophiles like sodium thiocyanate and sodium thiolates react well in displacements [46, 47] (equation 42)... 

AKZ640). Although some data (00UK642) support a ready hydration of the activated triple bond in a weakly basic medium, the latter route seems less probable, since the cyclization of hydrazine 22 is a monomolecular process (70AKZ640) and the hydrazine group is much more nucleophilic than water. 

Secondary alkyl halides Sjvj2 substitution occurs if a weakly basic nucleophile is used in a polar aprotic solvent, E2 elimination predominates if a strong base is used, and ElcB elimination takes place if the leaving group is two carbons away from a carbonyl group. Secondary allylic and benzyiic alkyl halides can also undergo S l and El reactions if a weakly basic nucleophile is used in a pro tic solvent. 

Such weakly basic nucleophiles as (CNljC" or (N02)3C will not react with CS (28). Jensen and Hendriksen reported syntheses, reactions, and IR, NMR, and electronic spectra of 1,1-ethendithiols and their derivatives (29). 

The reaction of 2-bromo-5-nitrothiazole with weakly basic secondary aliphatic amines gave the expected 2-amino products. The isomeric 5-bromo-2-nitrothiazole with such amines gave mixtures of the expected 5-amino products along with 2-aminated 5-nitrothiazole rearrangement products. A mechanism was proposed which involves the slow thermal isomerisation of the 5-bromo-2-nitrothiazole to the much more reactive 2-bromo isomer which competes, in the case of relatively weak amine nucleophiles, with direct but slow displacement of the 5-bromo group to form the normal displacement product <96JHC1191>. 

Complex 63 is stable in acidic to weakly basic aqueous solution. However, on addition of 0.1 M NaOH, nucleophilic attack on the /3-carbon atom takes place as shown in Eq. (16). This reaction, may also be considered to proceed via the initial a-hydroxylation, followed by dehydration to give the product. 

Hydroxylamines and alkylhydroxylamines possess high nucleophilicity and can react with a variety of primary and secondary alkylating agents. The reactivity of hydroxylamines in the majority of these reactions resembles that of primary and secondary amines. While hydroxylamine and Af-alkylhydroxylamines 1 are ambident nucleophiles, under neutral or weakly basic reaction conditions alkylation proceeds exclusively on nitrogen atom to give products of type 2 (equation 1). Deprotonation of the OH group of hydroxylamines results in O-alkylation products. 

The carbon nucleophiles in amine-catalyzed reaction conditions are usually rather acidic compounds containing two electron-attracting substituents. Malonic esters, cyanoacetic esters, and cyanoacetamide are examples of compounds which undergo condensation reactions under Knoevenagel conditions.115 Nitroalkanes are also effective nucleophilic reactants. The single nitro group sufficiently activates the a hydrogens to permit deprotonation under the weakly basic conditions. Usually, the product that is isolated is... 

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