Substitution/elimination reactions

Besides alkyl halides, many other types of compounds undergo substitution and elimination reactions. Substitutions and eliminations are introduced in this chapter using the alkyl halides as examples. In later chapters, we encounter substitutions and eliminations of other types of compounds. 

In this tandem allylic C-H bond activation, followed by an elimination reaction, substituted l-zircono-lZ,3 -dienes (zirconium moiety at the terminal position of the dienyl system) were easily prepared as unique isomers. With the idea of extending this methodology to the stereoselective synthesis of 3-zircono-1,3-diene (zirconium moiety at the internal position of the dienyl system), 119 was prepared and the reactivity was investigated with (1-butene)ZrCp2 21 (119 was obtained by carbocupration of the a-allyl alkoxy-allene, Scheme 35) [79]. When 119 was submitted to the tandem reaction, the diene 120 was isolated after hydrolysis as a unique ( ,Z) isomer in 75% isolated yield (Scheme 44). 

Combining Addition and Elimination Reactions (Substitutions at sp Centers)... 

Nucleophilic substitution of benzene itself is not possible but the halogeno derivatives undergo nucleophilic displacement or elimination reactions (see arynes). Substituents located in the 1,2 positions are called ortho- 1,3 meta- and 1,4 para-. 

N,N,N, N -tetramethyl-l,8,-naph-thalenediamiDe M.P. 51 C. A remarkably strong mono-acidic base (pKg 12-3) which is almost completely non-nucleophilic and valuable for promoting organic elimination reactions (e.g. of alkyl halides to alkenes) without substitution. 

Figure 3-3. Representative, simple examples of a substitution, an addition, and an elimination reaction showing the number, n, of reaction partners, and the change in n, An, during the reaction.

TosOH 4-methylbenzenesulfonic acid = p toluenesiilfonic acid, tosic acid X, Y leaving groups. e.g., halogen, RSOj, in substitution and elimination reactions... 

Zaitsev s rule as applied to the acid catalyzed dehydration of alcohols is now more often expressed in a different way elimination reactions of alcohols yield the most highly substituted alkene as the major product Because as was discussed in Section 5 6 the most highly substituted alkene is also normally the most stable one Zaitsev s rule is sometimes expressed as a preference for predominant formation of the most stable alkene that could arise by elimination... 

When we discussed elimination reactions in Chapter 5 we learned that a Lewis base can react with an alkyl halide to form an alkene In the present chapter you will find that the same kinds of reactants can also undergo a different reaction one m which the Lewis base acts as a nucleophile to substitute for the halo gen substituent on carbon... 

Nucleophilic substitution reactions of alkyl halides are related to elimination reactions m that the halogen acts as a leaving group on carbon and is lost as an anion The... 

Section 8 13 When nucleophilic substitution is used for synthesis the competition between substitution and elimination must be favorable However the normal reaction of a secondary alkyl halide with a base as strong or stronger than hydroxide is elimination (E2) Substitution by the Sn2 mechanism predominates only when the base is weaker than hydroxide or the alkyl halide is primary Elimination predominates when tertiary alkyl halides react with any anion... 

The least sterically hindered p hydrogen is removed by the base m Hofmann elim matron reactions Methyl groups are deprotonated m preference to methylene groups and methylene groups are deprotonated m preference to methmes The regioselectivity of Hofmann elimination is opposite to that predicted by the Zaitsev rule (Section 5 10) Elimination reactions of alkyltrimethylammonmm hydroxides are said to obey the Hofmann rule, they yield the less substituted alkene... 

Zaitsevs rule (Section 5 10) When two or more alkenes are capable of being formed by an elimination reaction the one with the more highly substituted double bond (the more sta ble alkene) is the major product Zwitterion (Section 27 3) The form in which neutral amino acids actually exist The ammo group is in its protonated form and the carboxyl group is present as a carboxylate... 

Synthesis. The first hiUy alkyl/aryl-substituted polymers were reported in 1980 via a condensation—polymeri2ation route. The method involves, first, the synthesis of organophosphine-containing alkyl or aryl substituents, followed by the ready oxidation of the phosphine to a phosphorane with leaving groups suitable for a 1,2-elimination reaction. This phosphorane is then thermally condensed to polymers in which all phosphoms atoms bear alkyl or aryl substituents. This condensation synthesis is depicted in Eigure 2 (5—7,64). 

Conjugate addition to a P-halogen substituted methaciylate results in an addition—elimination reaction which regenerates the tZ,/ -unsaturated moiety (19-21). 

True electrophilic substitution is very difficult in pyridopyridazines. For example, the [3,4-d] parent (286) is inert to hot 65% oleum (68AJC1291), and although formation of a 3-bromo derivative (308) was reported in the [2,3-d] series, it seems to have arisen by an addition-elimination reaction via the dibromide (309) (69AJC1745). Attempted chlorination led to ring opening. A similar effect was observed in the [3,4-d] system, where an 8-bromo derivative was obtained (77BSF665), and in iV-oxides of the pyrido[2,3-c]pyridazine and fused pyridazino[3,4-c]isoquinoline series (72JHC351). The formation of (311) from (310)... 

Chloroth1ete 1,1-dioxide is a potentially useful intermediate for the preparation of other 3-substituted thiete 1,1-dioxides via addition-elimination reactions. 

The stereochemistry of the most fundamental reaction types such as addition, substitution, and elimination are described by terms which specify the stereochemical relationship between the reactants and products. Addition and elimination reactions are classified as syn or anti, depending on whether the covalent bonds which are made or broken are on the same face or opposite faces of the plane of the double bond. 

This elimination reaction is the reverse of acid-catalyzed hydration, which was discussed in Section 6.2. Because a carbocation or closely related species is the intermediate, the elimination step would be expected to favor the more substituted alkene as discussed on p. 384. The El mechanism also explains the general trends in relative reactivity. Tertiary alcohols are the most reactive, and reactivity decreases going to secondary and primary alcohols. Also in accord with the El mechanism is the fact that rearranged products are found in cases where a carbocation intermediate would be expected to rearrange ... 

The general application of J elimination reactions will be considered later (section VII), however, the elimination from -substituted ketones proceeds particularly readily and is treated separately in this section. 

The opening of epoxides with neighboring keto groups, accompanied by vinylogous jS-elimination, has already been mentioned (section V). This is an extension of the jS-elimination reactions which occur when a,p- or jS,y-epoxy ketones are opened with acid or base. a,jS-Epoxy ketones give a-substituted a,jS-unsaturated ketones [(162), for example], and j5,y-epoxy ketones give y-substituted a,jS-unsaturated ketones [(163), for example] ... 

We have seen that an alkyl halide and a Lewis base can react together in either a substitution or an elimination reaction. 

Conversion to p-toluenesulfonate esters (Section 8.14) Alcohols react with p-toluenesulfonyl chloride to give p-toluenesulfonate esters. Sulfonate esters are reactive substrates for nucleophilic substitution and elimination reactions. The p-toluenesulfonate group is often abbreviated —OTs. 

Because the new carbon-carbon bond is formed by an SN2-type reaction the alkyl halide must not be sterically hindered. Methyl and primary alkyl halides work best secondary alkyl halides give lower yields. Tertiary alkyl halides fail, reacting only by elimination, not substitution. 

---