Elimination reactions competition with nucleophilic

Reaction with even harder nucleophiles such as organolithiums and Grignard reagents is substantially limited by virtue of the fact that these carbon nucleophiles add by direct attack at the metal center, as opposed to the softer carbon nucleophiles which add by attack on the allyl ligand. Direct metal addition can lead to the opening of alternative reaction pathways, e.g. 3-H elimination, in competition with reductive elimination which accomplishes nucleophile allylation (equation 40). 

Elimination reactions compete with substitution reactions. The competition occurs because the nucleophile is also a base. When it reacts as a base, it removes a proton from the carbon adjacent to the leaving group, resulting in the formation of the elimination product. 

A process that often competes with Sn2 displacements for organic systems is E2 (which stands for elimination, bimolecular ). When there is one or more hydrogens P with respect to the leaving group (see reaction 1.8) and the incoming nucleophile is a strong enough base, bimolecular elimination occurs, often in competition with nucleophilic displacement,... 

A study of debrominations of vtc-dibromides promoted by diaryl tellurides and din-hexyl telluride has established several key features of the elimination process the highly stereoselective reactions of e/7f/tro-dibromides are much more rapid than for fhreo-dibromides, to form trans- and cw-alkenes, respectively the reaction is accelerated in a more polar solvent, and by electron-donating substituents on the diaryl telluride or carbocation stabilizing substituents on the carbons bearing bromine. Alternative mechanistic interpretations of the reaction, which is of first-order dependence on both telluride and vtc-dibromide, have been considered. These have included involvement of TeAr2 in nucleophilic attack on carbon (with displacement of Br and formation of a telluronium intermediate), nucleophilic attack on bromine (concerted E2- k debromination) and abstraction of Br+ from an intermediate carbocation. These alternatives have been discounted in favour of a bromonium ion model (Scheme 9) in which the role of TeArs is to abstract Br+ in competition with reversal of the preequilibrium bromonium ion formation. The insensitivity of reaction rate to added LiBr suggests that the bromonium ion is tightly paired with Br. ... 

Alkyl halides undergo not only nucleophilic substitution but also elimination, and both reactions are carried out in basic reagents. Often substitution and elimination reactions occur in competition with each other. In general, most nucleophiles can also act as bases, therefore the preference for elimination or substitution is determined by the reaction conditions and the alkyl halide used. 

Nucleophilic displacement reactions are often competitive with other processes promoted by a nucleophile, such as addition-elimination, or proton abstraction and base-induced elimination in which the nucleophile acts as a strong base. This particular situation is especially true in reactions that also involve attack at an unsaturated carbon centre. The delicate interplay between these different mechanisms is in itself a matter of great interest, and as yet it has defied attempts to rationalize it on a quantitative basis. 

An important feature of many elimination reactions is that they occur with the same combinations of reagents that cause nucleophilic substitution. In fact, elimination and substitution often are competitive reactions. Therefore it should be no surprise that substitution and elimination have closely related mechanisms. 

Solvolysis of the R,R and R,S isomers of 2-bromo-9-(l-X-ethyl)fluorenes, X = Cl, Br, I, or OBs, in 25% (v/v) acetonitrile in water has been studied with respect to rates of formation of elimination products and of substitution products (X = OH or NHCOMe).142 The parent 9-(l-X-ethyl)fluorenes and the 2,2/-dibromo-9-(l-X-ethyl)-fluorenes were also studied. Various effects of leaving group and of the presence of nucleophiles on the competition between the reactions were observed and the Bronsted equation was applied to the results for the elimination reactions. A related study of solvolysis of 9-(X-methyl)fluorenes, X = I, Br, or Bs, was also carried out, in which the Swain-Scott equation was applied to nucleophilic selectivities in the S 2 reactions.143... 

When ArNH2 is o-phenylenediamine (80), the reaction is poorly catalysed by the second amino group, but it is mainly catalysed by an external molecule of amine. As a consequence, internal catalysis by an intramolecular complex such as 81 is unlikely. In competition with the substitution (Scheme 34), when the nucleophile (or a base) attacks a hydrogen atom in a fi position with respect to the leaving group, an elimination reaction takes place. 

The gas-phase base-induced elimination reaction of halonium ions was thoroughly investigated in radiolytic experiments22. Radiolytically generated acids C/JH5+ (n = 1,2) were allowed to react at 760 Torr with selected 2,3-dihalobutanes to form the halonium intermediates which, in the presence of trimethylamine, undergo base-induced bimolecu-lar elimination as shown in Scheme 6. This elimination reaction occurs in competition with unimolecular nucleophilic displacement to the cyclic halonium ion and subsequent rearrangement. Isolation and identification of the neutral haloalkenes formed and kinetic treatment of the experimental results indicated that 3-halo-1 -butene is formed preferentially with respect to the isomeric 2-halo-2-butenes and that the bimolecular elimination process occurs predominantly via a transition state with an anti configuration22. 

Russell and coworkers62,109,110 have shown that simple enolates undergo free radical-chain nucleophilic substitution reactions with a-chloronitroalkanes by an SRN2 rather than an S l mechanism, and competition with a chain dimerization process was also observed. Using two equivalents of the enolate anion in the reaction allows complete elimination of HN02 to yield a,/i-unsaturated ketones. The synthetic potential of these reactions has also been reported110. 

As we saw in Chapter 8, elimination reactions often compete with nucleophilic substitution reactions. Both reactions can be useful in synthesis if this competition can be controlled. This chapter discusses the two common mechanisms by which elimination reactions occur, the stereochemistry of the reactions, the direction of the elimination, and the factors that control the competition between elimination and substitution. Based on these factors, procedures are presented that can be used to minimize elimination if the substitution product is the desired one or to maximize elimination if the alkene is the desired product. 

The lithium salt of indole can be alkylated or vinylated by ethylene complexed with PdCl2. These reactions follow patterns established for Pd-catalyzed addition of many other nucleophiles and presumably involve an organopalladium intermediate which can either undergo elimination to form the N-vinylindole or reduction to give the N-ethylindole as shown in Scheme 21 (81JOC2215). Although at the present time this procedure would seldom be competitive with the use of SN2 conditions for alkylation, the development of vinylation conditions which were catalytic in Pd might be useful. 

Examples of the solvent-dependent competition between nucleophilic substitution and / -elimination reactions [i.e. SnI versus Ei and Sn2 versus E2) have already been given in Section 5.3.1 [cf. Table 5-7). A nice example of a dichotomic y9-elimination reaction, which can proceed via an Ei or E2 mechanism depending on the solvent used, is shown in Eq. (5-140a) cf. also Eqs. (5-20) and (5-21) in Section 5.3.1. The thermolysis of the potassium salt of racemic 2,3-dibromo-l-phenylpropanoic acid (A), prepared by bromine addition to ( )-cinnamic acid, yields, in polar solvents [e.g. water), apart from carbon dioxide and potassium bromide, the ( )-isomer of l-bromo-2-phenylethene, while in solvents with low or intermediate polarity e.g. butanone) it yields the (Z)-isomer [851]. 

Katritzky and coworkers have extensively developed the activation of amines by reaction with pyry-lium salts to provide (V-alkyl (or N-aryl) pyridinium compounds. When buttressing substituents were present to discourage attack on the pyridine ring, the N-alkyl substituent was subject to displacement and elimination processes. In general, primary alkyl substituents reacted with most nucleophiles in a normal 5n2 process as shown in Scheme 12, whereas competition between substitution and elimination took place with the secondary analogs, with elimination dominating the reactions starting from cycloalkyl-amines. 

The competitive elimination (ET) and substitution (iSn2) reactions of cyclohexyl tosylate with triphenylphosphine have been examined. Triphenylphosphine is considered to be representative of neutral weak bases which have good nucleophilic afiinity for carbon, but it is a poor reagent for elimination when compared with anionic weak bases that are also good carbon nucleophiles. The reaction of triphenylphosphine with cyclohexyl bromide occurs with almost complete substitution. Tertiary phosphines react with fluorosulphonyl isocyanate and with isothiocyanates to form the zwitterionic adducts (56) and (57). 

A few cases of nucleophilic additions to P-ketophosphonates have been reported. When the a-carbon atom to phosphorus is fully substituted, it appears unlikely that the reaction at phosphorus is competitive with the addition to carbonyl group. Thus, treatment of diethyl 1-fluoro-1-ethoxy-carbonyl-2-ethoxycarbonyl-2-oxoethylphosphonate with Grignard reagents at low temperature in THF gives an ( )/(/) mixture of a-fluoro-a,P-unsaturated diesters in 49-68% yields. The initial step is the nucleophilic attack of Grignard reagent at the carbonyl group, followed by intramolecular elimination of diethyl phosphate (Scheme 7.104). ° ... 

This reaction occurs (in competition with hydrolysis) preferentially in compounds in which a relatively acidic proton is located at a carbon atom adjacent to the carbon atom carrying the leaving group (i.e., the halogen). These criteria are optimally met in 1,1,2,2-tetrachloroethane, where the four electron-withdrawing chlorine atoms render the hydrogens more acidic and, simultaneously, hinder nucleophilic attack. In aqueous solution, 1,1,2,2-tetrachloroethane ii converted more or less quantitatively to trichloroethylene (Haag and Mill, 1987) by a so-called E2 (elimination, bimolccular) mechanism that is, the elimination takes place in a concerted reaction with OH ... 

Key point. Alkyl halides are composed of an alkyl group bonded to a halogen atom (X = F, Cl, Br, I). As halogen atoms are more electronegative than carbon, the C-X bond is polar and nucleophiles can attack the slightly positive carbon atom. This leads to the halogen atom being replaced by the nucleophile in a nucleophilic substitution reaction, and this can occur by either an SN1 (two-step) mechanism or an Sn2 (concerted or one-step) mechanism. In competition with substitution is elimination, which results in the loss of HX from alkyl halides to form alkenes. This can occur by either an El (two-step) mechanism or an E2 (concerted) mechanism. The mechanism of the substitution or elimination reaction depends on the alkyl halide, the solvent and the nucleophile/base. 

Alkyl halides undergo competitive substitution and elimination reactions. The ratio of products derived from substitution and elimination depends on the nature of the alkyl halide, the base/nucleophile, the solvent and the temperature. SN2 reactions are normally in competition with E2 reactions, while SN1 reactions are normally in competition with El reactions. 

Part Z The Mechanism of Substitution and Part 3 Elimination and Addition Pathways and Products are concerned with organic reaction mechanisms. Curly arrows are introduced and the key features of the two common mechanisms of nucleophilic substitution are reviewed. Including kinetic features, stereochemical outcome and reaction coordinate diagrams. This leads to a discussion of the features of El and E2 elimination reactions. The book finishes with a discussion of the factors that affect the competition between substitution and elimination reactions. Much of the teaching of substitution mechanisms Is carried out via interactive CD-ROM activities. 

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