Substitution reactions, inhibition nucleophilic

The synthesis of polyhalide salts, R4NX , used in electrophilic substitution reactions, are described in Chapter 2 and H-bonded complexed salts with the free acid, R4NHX2, which are used for example in acid-catalysed cleavage reactions and in electrophilic addition reactions with alkenes, are often produced in situ [33], although the fluorides are obtained by modification of method I.I.I.B. [19, 34], The in situ formation of such salts can inhibit normal nucleophilic reactions [35, 36]. Quaternary ammonium chlorometallates have been synthesized from quaternary ammonium chlorides and transition metal chlorides, such as IrClj and PtCl4, and are highly efficient catalysts for phase-transfer reactions and for metal complex promoted reactions [37]. 

The application of phase-transfer catalysis to the Williamson synthesis of ethers has been exploited widely and is far superior to any classical method for the synthesis of aliphatic ethers. Probably the first example of the use of a quaternary ammonium salt to promote a nucleophilic substitution reaction is the formation of a benzyl ether using a stoichiometric amount of tetraethylammonium hydroxide [1]. Starks mentions the potential value of the quaternary ammonium catalyst for Williamson synthesis of ethers [2] and its versatility in the synthesis of methyl ethers and other alkyl ethers was soon established [3-5]. The procedure has considerable advantages over the classical Williamson synthesis both in reaction time and yields and is certainly more convenient than the use of diazomethane for the preparation of methyl ethers. Under liquidrliquid two-phase conditions, tertiary and secondary alcohols react less readily than do primary alcohols, and secondary alkyl halides tend to be ineffective. However, reactions which one might expect to be sterically inhibited are successful under phase-transfer catalytic conditions [e.g. 6]. Microwave irradiation and solidrliquid phase-transfer catalytic conditions reduce reaction times considerably [7]. 

Azide ion is a modest leaving group in An + Dn nucleophilic substitution reactions, and at the same time a potent nucleophile for addition to the carbocation reaction intermediate. Consequently, ring-substituted benzaldehyde g m-diazides (X-2-N3) undergo solvolysis in water in reactions that are subject to strong common-ion inhibition by added azide ion from reversible trapping of an o -azido carbocation intermediate (X-2 ) by diffusion controlled addition of azide anion (Scheme... 

A comparison of the relative reactivities of norbornane and silanorbor-nane illustrates the point. 1-Halonorbornane derivatives are very resistant to nucleophilic substitution reactions under strenuously applied S l and Sn2 conditions. The low reactivities of these compounds result from the cage structure that prohibits deformation to the planar geometry required for the carbocation intermediates of unimolecular reactions and inhibits the backside attack required for bimolecular substitutions at carbon. 

The triarylaminium salts [N(aryl)3][X] in which the para position is substituted (in order to inhibit nucleophilic reactions at that position) are among the most useful oxidants because they are strong, almost innocent oxidants known for a range of standard redox potentials from 0.16 V to -1.76 V relative to FeCp2 depending of the nature and number of substituents (Table 10), and they are easily accessible by oxidation of the triarylamine in CH2CI2 using [NO] salts, silver salts in the presence... 

The rate enhancements observed in these nucleophilic aromatic substitution reactions when using crown-complexed ions and tetraalkylam-monium ions are indeed not surprising. Many examples are known of increased reactivity in nucleophilic substitutions due to complexation with crown compounds (24), also in SNAr reactions (25, 26). In our system, however, this normal effect is accompanied by an inhibiting effect on the competing reduction path, which is discussed under Reduction Channel. 

Chapters 11 and 12 discuss reactions of alkyl halides to give either substitution or elimination products. It is clear from Chapter 12 that elimination occurs when the nucleophile is also a strong base and when substitution is inhibited due to steric hindrance. There are many cases in which substitution and elimination compete, particularly when the substrate is a secondary alkyl halide. The solvent plays an important role in these reactions, and solvent identification is a key parameter for distinguishing bimolecular versus unimolecu-lar (ionization) processes. The nature of the alkyl halide (1°, 2°, or 3°) is important, as is the strength of the nucleophile and whether or not that nucleophile can also react a strong base. This chapter will discuss those factors that influence both substitution and elimination, as well as introduce several assumptions that will help make predictions as to the major product. 

The oxidation of hexacyanoferrate(n) by [PaOg] " is strongly inhibited by CN, and a substitution process is again involved [reaction (18)]. Nucleophilic sub-... 

Nucleophilic substitution reactions are one of the most important classes of reactions in organic chemistry. In particular, 8 2 reactions are among the most extensively stndied chemical processes in solution and in the gas phase, both theoretically and experimentally. The history of the study of these reactions closely parallels (and is sometimes responsible for) the development of concepts such as structure-reactivity relationships, linear free-energy relationships, steric inhibition, kinetics as a probe of mechanism, stereochemistry as a probe of mechanism and solvent effects. 

In the area of nucleophilic acyl substitution using C-nucleophiles, Baba et al. found that the allylation of acid chlorides using allylic tin catalyzed by InCla stop at the allylketone product when the allylic tin compound is terminally substituted, otherwise for y-unsubstituted allylic tins, further allylation of the allylketone would occur [148]. Addition of PPh3 for y-unsubstituted allylic tin reactions would halt the allylation at the allylketone stage, but would inhibit reactions of y-substituted allylic tin (Figure 8.61). A mechanism was proposed involving transmetallation to form an allylic indium species followed by coordination of PPh3 with the indium center. 

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). 

The reaction of an alkyl halide or los3 late with a nucleophiJe/base results eithe in substitution or in diminution. Nucleophilic substitutions are of two types S 2 reactions and SN1 reactions, in the SN2 reaction, the entering nucleophih approaches the halide from a direction 180° away from the leaving group, result ing in an umbrella-like inversion of configuration at the carbon atom. The reaction is kinetically second-order and is strongly inhibited by increasing stork bulk of the reactants. Thus, S 2 reactions are favored for primary and secondary substrates. 

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