Sensitivities to nucleophilicity

Charge diagrams suggest that the 2-amino-5-halothiazoles are less sensitive to nucleophilic attack on 5-position than their thiazole counterpart. Recent kinetic data on this reactivity however, show, that this expectation is not fulfilled (67) the ratio fc.. bron.c.-2-am.noih.azoie/ -biomoth.azoie O"" (reaction with sodium methoxide) emphasizes the very unusual amino activation to nucleophilic substitution. The reason of this activation could lie in the protomeric equilibrium, the reactive species being either under protomeric form 2 or 3 (General Introduction to Protomeric Thiazoles). The reactivity of halothiazoles should, however, be reinvestigated under the point of view of the mechanism (1690). 

In a third step, the anhydrobase reacts on the carbon which is the most sensitive to nucleophilic attack. The unstable intermediate 23 splits into aminothiophenol and trimethine thiazolocyanine 124). 

Isoxazolium salts can be prepared by reaction with alkyl iodides or sulfates, although the low basicity of isoxazoles and their sensitivity to nucleophilic attack may necessitate special care. Isoxazolium salts containing bulky Af-substituents can be prepared by the reaction of isoxazoles with alcohols in the presence of perchloric acid. For example, the reaction of 3,5-dimethylisoxazole (53) with some alcohols in the presence of 70% perchloric acid gave isoxazolium salts, (54a) in 29%, (54b) in 57% and (54c) in 82% yield 79AHC(25)147, 68JOC2397). Attempts to quaternize 3,5-dimethyl-4-nitroisoxazole failed 71JCS(B)2365). 

Bimanes containing one or two chloro- or bromomethyl groups are very sensitive to nucleophilic substitution and their reactivity was discussed in CHEC-II(1996) <1996CHEC-II(8)747>. The use of monochloro and monobromo-bimane in analytical chemistry (Section 12.10.15.4) is mostly based on this reactivity. 

New 3-desoxyanthocyanidins have been prepared according to a Grignard reaction of some flavones with appropriate alkyl- and aryl-magnesium bromides. The reaction of 5,7-dihydroxyflavone (chrysin) with an excess of phenylmagnesium bromide in THF under reflux conditions, followed by hydrochloric acid hydrolysis, afforded 1 in Scheme 10.2. Flavylium salts bearing a substituent at the 4-position are important compounds since they are known to be less sensitive to nucleophiles, especially water, and they give only minor amounts of the colorless pseudobases. ... 

The red thermally unstable crystals are soluble in organic solvents. Since the complex is extremely sensitive to nucleophiles, traces of moisture and alcohols have to be removed from all solvents before use. The complex must be stored under nitrogen below -20°. IR Vqq at 2070 (m), 1952 (vs, br), 1942 (vs, br) cm 1 in pentane, H NMR (TMS, C6D6, 60 MHz) tsjch3 at 9.93 ppm (singlet), tCHj at 8.11 ppm (singlet), rCtH< at 2.68 ppm (doublet) + 3.08 ppm (doublet). 

It is well known 113,14 20 25> that the addition of hydroxyl-containing compounds (water, alcohols, phenols, acids) considerably promotes the interaction of epoxy compounds with amines and other nucleophilic reagents. In this case, the epoxy ring carbon atom becomes more sensitive to nucleophilic attack. The reaction proceeds through a trimolecular transition state initially suggested by Smith26 27) for the reactions of epoxy compounds with amines2... 

The electro-attractive alkoxo groups render metal alkoxides very sensitive to nucleophilic attack.6 They are extremely susceptible to hydrolysis, which under controlled conditions yields oxo alkoxides they require strictly anhydrous conditions of handling. 

Some examples of the behavior of unsaturated ketonucleosides under alkaline conditions have also been reported. The enol acetate 61a is more stable than the parent ketonucleoside 36a. In 0.1 M methanolic sodium hydroxide, free theophylline was detected only after 4 h, by which time, loss of the acetyl group was complete a reaction time of more than 18 h was needed for complete cleavage of the glycosylic bond.51 In alcoholic solution, the unsaturated 4 -ketonucleoside 66 was very sensitive to nucleophilic attack, and decomposed rapidly, with elimination of the nitrogenous base.31 Thus, treatment with sodium borohydride at — 70° led to complete decomposition within 10 min but, when sodium borohydride was added to a solution of 66 in 1,2-dichloroethane containing acetic acid, fast reduction occurred, and no degradation was observed.31... 

Benzo fused rings containing two or more electron-donating heteroatoms along with the boron atom, e.g. (57), are more stable to hydrolysis and alcoholysis than the corresponding open-chain derivatives, yet they are more or less sensitive to nucleophilic breakdown. For example, compound (77) is solvolyzed within five days in alcoholic solution at room... 

Primary and secondary aliphatic amines can be linked to polymeric supports by acid-labile linkers or by linkers sensitive to nucleophiles. Linkers cleavable by light or by transition metal catalysis have also been described. The main types of linker for amines are sketched in Figure 3.24. 

Like all cation radicals, ammoniumyls are sensitive to nucleophiles (to reactants or admixtures). At the same time, l,l,l,3,3,3-hexafluoropropan-2-ol as a solvent drastically curtails nucleophilic reactivity and provides good integrity of the tris(4-bromophenyl)am-moniumyl at ambient temperatures (Eberson, Hartshorn et al. 1996). 

Epoxides are sensitive to nucleophilic ring-opening reactions. Phenoxide ion attacks the less hindered carbon to yield l-phenoxy-2-propanol. 

This product, like the diimide complex from which it is prepared, is very sensitive to nucleophilic reagents and should not be left in contact with solvents unnecessarily. 

Alkynyliodonium ions, 1 and 2, are hypervalent iodine species in which one or two alkynyl ligands are bound to a positively charged iodine(III) atom. They are sensitive to nucleophiles, especially at the /1-carbon atom(s) of the alkynyl ligand(s), and for that reason, the isolation of stable alkynyliodonium salts generally requires the incorporation of nucleofugic anions. A list of known alkynyliodonium compounds (i.e. as of 4/1/94), containing 134 iodonium salts derived from 103 iodonium ions, and references (5-45) to their preparation and characterization are presented in Table 1. Among these compounds, alkynyl(phenyl)iodonium sulfonates and tetrafluoroborates are the most common, while alkynyl(alkyl)iodonium salts of any kind are unknown. 

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