Subject nucleophilic substitution

The mechanisms by which nucleophilic substitution takes place have been the subject of much study Extensive research by Sir Christopher Ingold and Edward D Hughes and their associates at University College London during the 1930s emphasized kinetic and stereochemical measurements to probe the mechanisms of these reactions... 

A large number of nucleophilic substitution reactions involving interconversions of pyridopyrimidines have been reported, the majority of which involve substituents in the pyrimidine ring. This subject has been reviewed previously in an earlier volume in this series which dealt with the theoretical aspects of nucleophilic re-activiti in azines, and so only a summary of the nucelophilic displacements of the substituent groups will be given here. In general, nucleophilic substitutions occur most readily at the 4-position of pyrido-... 

The least squares value for the p constant obtained by this procedure is +6.2 it wiU be obviously subject to change as more meta and epi substituents become available. Only the cata-NO group was excluded from the above plot because it causes a strongly enhanced resonance effect in nucleophilic substitution (Section IV,C, l,a) and an anomalous effect of uncertain origin in the dissociation of carboxylic acids. It can be assumed that the reaction constant for 4-chloro-... 

To derive the maximum amount of information about intranuclear and intemuclear activation for nucleophilic substitution of bicyclo-aromatics, the kinetic studies on quinolines and isoquinolines are related herein to those on halo-1- and -2-nitro-naphthalenes, and data on polyazanaphthalenes are compared with those on poly-nitronaphthalenes. The reactivity rules thereby deduced are based on such limited data, however, that they should be regarded as tentative and subject to confirmation or modification on the basis of further experimental study. In many cases, only a single reaction has been investigated. From the data in Tables IX to XVI, one can derive certain conclusions about the effects of the nucleophile, leaving group, other substituents, solvent, and comparison temperature, all of which are summarized at the end of this section. 

Comprehensive work in this field has been done by Slovak authors (98MI1, 95M1359, 96CCC269, 96CCC371, 97CCC99). They prepared 2-substituted (H, Me, Ph) 4-, 5-, 6-, and 7-nitrobenzoxazoles, which were then reduced to amines (not isolated) and subjected to subsequent nucleophilic substitution with activated enol ethers such as alkoxymethylene derivatives of malonic acid esters and nitrile, 3-oxobutanoic acid esters, pentanedione, or cyanoacetic acid esters to yield aminoethylenes 8. 

In the reaction of amines such as NH3, NH2NH2, MeNH2, C6HUCH2NH2, and Ph(OMe)NH2, only monosubstitution can be obtained even in the presence of a large excess of the amine. This is taken into account by the deprotonation of the acidic monosubstituted complex by free amine leading to an iminocyclohexadienyl complex. The latter cannot be subjected to nucleophilic substitution of the second... 

Carbonyl reactions are extremely important in chemistry and biochemistry, yet they are often given short shrift in textbooks on physical organic chemistry, partly because the subject was historically developed by the study of nucleophilic substitution at saturated carbon, and partly because carbonyl reactions are often more difhcult to study. They are generally reversible under usual conditions and involve complicated multistep mechanisms and general acid/base catalysis. In thinking about carbonyl reactions, 1 find it helpful to consider the carbonyl group as a (very) stabilized carbenium ion, with an O substituent. Then one can immediately draw on everything one has learned about carbenium ion reactivity and see that the reactivity order for carbonyl compounds ... 

Nucleophilic Substitution of xi-Allyl Palladium Complexes. TT-Allyl palladium species are subject to a number of useful reactions that result in allylation of nucleophiles.114 The reaction can be applied to carbon-carbon bond formation using relatively stable carbanions, such as those derived from malonate esters and (3-sulfonyl esters.115 The TT-allyl complexes are usually generated in situ by reaction of an allylic acetate with a catalytic amount of fefrafcz s-(triphenylphosphine)palladium... 

Tetranitro derivative 90 (z-TACOT Section 12.10.15.5) treated with methanolic sodium methoxide at ambient temperature does not lead to simple product of nucleophilic substitution of a nitro group but provides compound 92. Its formation can be rationalized by introduction of the methoxy group into the 1-position, followed by scission of the remote triazole ring of 91 to give the final product. Compound 90 subjected to the vicarious nucleophilic substitution (VNS) conditions using either hydroxylamine or trimethylhydrazinium iodide gives a very insoluble red solid, which was identified as l,3,7,9-tetraamino-2,4,8,10-tetranitrobenzotriazolo[2,l- ]benzotriazole 93 (Scheme 5) <1998JOC3352>. 

The chemistry of diazines remains an area of intense interest, both academic and industrial, with applications in many areas, from biomedical to materials science and electronics. They are versatile, having very varied reactivity, giving many opportunities for manipulation of substituents. Nucleophilic substitutions, electrophilic substitution in oxy and amino derivatives, organometallic and transition metal-catalysed coupling reactions are all subjects of substantial research effort. There are obvious similarities in reactivity of the three diazine systems but also many interesting and practically important, often subtle, differences. 

A diverse group of organic reactions catalyzed by montmorillonite has been described and some reviews on this subject have been published.19 Examples of those transformations include addition reactions, such as Michael addition of thiols to y./bunsatu rated carbonyl compounds 20 electrophilic aromatic substitutions,19c nucleophilic substitution of alcohols,21 acetal synthesis196 22 and deprotection,23 cyclizations,19b c isomerizations, and rearrangements.196 24... 

In reactions with azides, ketones are directly converted to 5-hydroxytriazolines. Ketone enolate 247, generated by treatment of norbornanone 246 with LDA at 0°C, adds readily to azides to provide hydroxytriazolines 248 in 67-93% yield. Interestingly, l-azido-3-iodopropane subjected to the reaction with enolate 247 gives tetracyclic triazoline derivative 251 in 94% yield. The reaction starts from an electrophilic attack of the azide on the ketone a-carbon atom. The following nucleophilic attack on the carbonyl group in intermediate 249 results in triazoline 250. The process is completed by nucleophilic substitution of the iodine atom to form the tetrahydrooxazine ring of product 251 (Scheme 35) <2004JOC1720>. 

Some derivatives of the [l,2,4]triazolo[4,3-3]pyridazine ring system 33 were subjected to a special type of nucleophilic substitution called vicarious nucleophilic substitution (VSN) <2006TL4259>. In the course of this transformation a formal substitution of az aromatic hydrogen atom - occurring via an addition-elimination mechanism - takes place. 

In contrast to the relative chemical stability of mono-epoxides, diol epoxides of fatty acids (10.52), which are formed from di-epoxides by EH, are subject to a different fate. In such metabolites, intramolecular nucleophilic substitution may occur, such that oxirane opening is accompanied by formation of a tetrahydrofuran ring [134], Such reactions of intramolecular nucleophilic substitution are discussed in detail in Sect. 11.9. In the case of diol epoxides of fatty acids, the resulting tetrahydrofuran-diols (10.53) are part of a much larger ensemble of oxygenated metabolites of fatty acids, the potential cytotoxicities of which are being evaluated [135]. 

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... 

We hope that this review of chiral sulfur compounds will be useful to chemists interested in various aspects of chemistry and stereochemistry. The facts and problems discussed provide numerous possibilities for the study of additional stereochemical phenomena at sulfur. As a consequence of the extent of recent research on the application of oiganosulfur compounds in synthesis, further developments in the field of sulfur stereochemistry and especially in the area of asymmetric synthesis may be expected. Looking to the future, it may be said that the static and dynamic stereochemistry of tetra- and pentacoordinate trigonal-bipyramidal sulfur compounds will be and should be the subject of further studies. Similarly, more investigations will be needed to clarify the complex nature of nucleophilic substitution at tri- and tetracoordinate sulfur. Finally, we note that this chapter was intended to be illustrative, not exhaustive therefore, we apologize to the authors whose important work could not be included. 

Organosulfur chemistry is presently a particularly dynamic subject area. The stereochemical aspects of this field are surveyed by M. Mikojajczyk and J. Drabowicz. in the fifth chapter, entitled Qural Organosulfur Compounds. The synthesis, resolution, and application of a wide range of chiral sulfur compounds are described as are the determination of absolute configuration and of enantiomeric purity of these substances. A discussion of the dynamic stereochemistry of chiral sulfur compounds including racemization processes follows. Finally, nucleophilic substitution on and reaction of such compounds with electrophiles, their use in asymmetric synthesis, and asymmetric induction in the transfer of chirality from sulfur to other centers is discussed in a chapter that should be of interest to chemists in several disciplines, in particular synthetic and natural product chemistry. 

Chlordane is subject to hydrolysis via the nucleophilic substitution of chlorine by hydroxyl ions to yield 2,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4,7-methano-l//-indene which is resistant to hydrolysis (Kollig, 1993). The hydrolysis half-life at pH 7 and 25 °C was estimated to be >197,000 yr (Ellington et ah, 1988). 

Position 3 of anhydro 2-methyl-4-hydroxy-5,6,7,8-tetrahydropyrido[l,2-6]pyridazinium hydroxide (57) was subjected to both electrophilic and nucleophilic substitution to give 58-61 (71CPB159). Treatment of 57 with H2O2 gave the 3-hydroxy derivative 62. 

Compounds with a low HOMO and LUMO (Figure 5.5b) tend to be stable to selfreaction but are chemically reactive as Lewis acids and electrophiles. The lower the LUMO, the more reactive. Carbocations, with LUMO near a, are the most powerful acids and electrophiles, followed by boranes and some metal cations. Where the LUMO is the a of an H—X bond, the compound will be a Lowry-Bronsted acid (proton donor). A Lowry-Bronsted acid is a special case of a Lewis acid. Where the LUMO is the cr of a C—X bond, the compound will tend to be subject to nucleophilic substitution. Alkyl halides and other carbon compounds with good leaving groups are examples of this group. Where the LUMO is the n of a C=X bond, the compound will tend to be subject to nucleophilic addition. Carbonyls, imines, and nitriles exemplify this group. 

On p. 341 it was pointed out that nucleophilic substitutions proceed so slowly at an aromatic carbon that the reactions of Chapter 10 are not feasible for aromatic substrates. There are, however, exceptions to this statement, and it is these exceptions that form the subject of this chapter.1 Reactions that are successful at an aromatic substrate are largely of four kinds ... 

The lack of reactivity of 3-halo substituents under non-radical nucleophilic substitution conditions allows differential functionalization of pyri-dines by 3-umpolung and 2-nucIeophilic substitution processes. Thus, treatment of 2-fluoro-3-iodopyridine (189) with oxygen or amine nucleophiles affords products 191 which, upon subjection of SRN1 reactions with carbon, phosphorus, and sulfur systems, give 2,3-difunctionalized pyri-dines 192 (Scheme 56) (88JOC2740). 

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