Ring-substituted derivatives, nucleophilic

The photoinduced generation of o-quinonemethides from o-hydro-xybenzylalcohols (see Sec. 15.4.1.3) has been exploited in the intramolecular cycloaddition to a double bond for the synthesis of the hexahydrocanna-binol ring system. The reaction gives the desired product in >80% yield in acetonitrile-water, provided that the tethered alkenes are sufficiently electron-rich (trisubstituted). With less substituted derivatives nucleophilic addition by the solvent on the intermediate quinonemethide prevails over cycloaddition [300]. 

Pyridine-l-oxide and some of its ring-substituted derivatives act as nucleophiles and generally give the corresponding 2-(l,2,2,2-tetrafluoro)pyndmes upon reaction with hexajluoropropene [21,22]. The reaction involves a novel rearrangement, as illustrated in the proposed mechanism (equation 10 and Table 1) Initial attack of the fluoroolefin by the oxygen produces an intermediate 1,5 dipole, followed by collapse and extrusion of carbonyl fluoride... 

The anilinium ion and its ring-substituted derivatives have been found to be considerably more effective as catalysts in semicarbazone and oxime formation than their pJC values would lead one to predict. Investigation showed that they are not functioning as classical general acid catalysts but as nucleophilic cabdysts, through the formation of reactive Schiff base intermediates . Similar Schiff base intermediates have been proposed to occur in the amine-catalyzed enoliza-tion of acetone . In reactions (39 and 40) the overall rate of... 

Anomalous Fischer cyclizations are observed with certain c-substituted aryl-hydrazones, especially 2-alkoxy derivatives[l]. The products which are formed can generally be accounted for by an intermediate which w ould be formed by (ip50-substitution during the sigmatropic rearrangement step. Nucleophiles from the reaction medium, e.g. Cl or the solvent, are introduced at the 5-and/or 6-position of the indole ring. Even carbon nucleophiles, e.g. ethyl acetoacelate, can be incorporated if added to the reaction solution[2]. The use of 2-tosyloxy or 2-trifluoromethanesulfonyloxy derivatives has been found to avoid this complication and has proved useful in the preparation of 7-oxygen-ated indoles[3]. 

As we ve just seen nucleophilic ring opening of ethylene oxide yields 2 substituted derivatives of ethanol Those reactions involved nucleophilic attack on the carbon of the ring under neutral or basic conditions Other nucleophilic ring openings of epoxides like wise give 2 substituted derivatives of ethanol but either involve an acid as a reactant or occur under conditions of acid catalysis... 

Rifamycin S also undergoes conjugate addition reactions to the quinone ring by a variety of nucleophiles including ammonia, primary and secondary amines, mercaptans, carbanions, and enamines giving the C-3 substituted derivatives (38) of rifamycin SV (117,120,121). Many of the derivatives show excellent antibacterial properties (109,118,122,123). The 3-cycHc amino derivatives of rifamycin SV also inhibit the polymerase of RNA tumor vimses (123,124). 

In this section three main aspects will be considered. Firstly, the basic strengths of the principal heterocyclic systems under review and the effects of structural modification on this parameter will be discussed. For reference some pK values are collected in Table 3. Secondly, the position of protonation in these carbon-protonating systems will be considered. Thirdly, the reactivity aspects of protonation are mentioned. Protonation yields in most cases highly reactive electrophilic species. Under conditions in which both protonated and non-protonated base co-exist, polymerization frequently occurs. Further ipso protonation of substituted derivatives may induce rearrangement, and also the protonated heterocycles are found to be subject to ring-opening attack by nucleophilic reagents. 

Ethylene oxide is a very reactive substance. It reacts rapidly and exothermically with anionic nucleophiles to yield 2-substituted derivatives of ethanol by cleaving the carbon-oxygen bond of the ring ... 

The compounds referred to as azolides are heterocyclic amides in which the amide nitrogen is part of an azole ring, such as imidazole, pyrazole, triazole, tetrazole, benzimidazole, benzotriazole, and their substituted derivatives. In contrast to normal amides, most of which show particularly low reactivities in such nucleophilic reactions as hydrolysis, alcoholysis, aminolysis, etc., the azolides are characterized by high reactivities in reactions with nucleophiles within the carbonyl group placing these compounds at about the same reactivity level as the corresponding acid chlorides or anhydrides. 11... 

One of the most important reactions of purines is the bromination of guanine or adenine at the C-8 position. It is this site that is the most common point of modification for bioconjugate techniques using purine bases (Figure 1.53). Either an aqueous solution of bromine or the compound N-bromosuccinimide can be used for this reaction. The brominated derivatives then can be used to couple amine-containing compounds to the pyrimidine ring structure by nucleophilic substitution (Chapter 27, Section 2.1). 

Reactions with dialdehydes allow the introduction of two additional rings in one step. Thus, condensation of 1 -(2-aminoethyl)pyrrole with glutaraldehyde and benzotriazole gives tricyclic intermediate 627 in which the benzotriazolyl moiety can be readily substituted with nucleophiles to give products 628 (Scheme 97) <2002JOC8220>. Condensation of ethyl ester of L-tryptophan with 2,5-dimethoxytetrahydrofuran and benzotriazole in acetic acid gives tetracyclic intermediate 629 which upon treatment with nucleophiles (silyl derivatives) is converted to products 630 <1999T3489>. 

The linearly fused oxadiazoloquinazoline derivative 90 also underwent ring opening with nucleophiles treatment of a toluene solution of this compound with tetrahydropyridine (refluxing conditions for 15 min followed by storage overnight at room temperature) yielded the urea-substituted quinazoline compound 91 in almost quantitative yield <2000S2009>. 

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