1,4 - Addition-eliminations 670 1,2-ADDITIONS

Many RjGe-Ir species are thus available starting from 4-coordinate Ir(I). Some reactions involve more complex addition-elimination-addition sequences, as in Eq. (d), to give (R3Ge) Ir species. It seems likely that the initial step is a trans addition to give an isomer with trans-phosphines, but later rearrangements, e.g., to C, may occur. The basic pathway is the same for Ir(I) as for Pt(II), but since 6-coordinate Ir(III) is stable, subsequent reductive eliminations are rarer. 

Moreover, the reaction of /3-alkoxyalkylidenemalonic esters with organomagne-sium compounds leads to the dialkylated product (addition-elimination-addition), whatever the stoichiometry of the reactants (Scheme 13.34). With organomanganese reagents such a drawback is never observed and it is possible to prepare at 0 C the monoaddition product. It is also possible to obtain the addition-elimination product after acidic hydrolysis. 

As regards reaetions other than nitration brought about by some of these systems, especially noteworthy are the addition processes undergone by eertain indole derivatives when treated with solutions of nitrie aeid in aeetie aeid. Produets inelude glycols, nitro-alcohols, and nitro-alcohol acetates. Such additions might well be encountered with some polynuclear aromatie eompounds, and with sueh eompounds the possibility of nitration by addition-elimination must always be borne in mind. 

More information has appeared concerning the nature of the side reactions, such as acetoxylation, which occur when certain methylated aromatic hydrocarbons are treated with mixtures prepared from nitric acid and acetic anhydride. Blackstock, Fischer, Richards, Vaughan and Wright have provided excellent evidence in support of a suggested ( 5.3.5) addition-elimination route towards 3,4-dimethylphenyl acetate in the reaction of o-xylene. Two intermediates were isolated, both of which gave rise to 3,4-dimethylphenyl acetate in aqueous acidic media and when subjected to vapour phase chromatography. One was positively identified, by ultraviolet, infra-red, n.m.r., and mass spectrometric studies, as the compound (l). The other was less stable and less well identified, but could be (ll). 

Arenediazonium salts are also used for the couplina[563], (Z)-Stilbene was obtained unexpectedly by the reaction of the ti-stannylstyrene 694 by addition-elimination. This is a good preparative method for cu-stilbene[564]. The rather inactive aryl chloride 695 can be used for coupling with organostannanes by the coordination of Cr(CO)3 on aromatic rings[3.565]. 

This reactivity pattern underlies a group of important synthetic methods in which an a-substituent is displaced by a nucleophile by an elimination-addition mechanism. Even substituents which are normally poor leaving groups, such as alkoxy and dialkylamino, are readily displaced in the indole series. 

An important method for construction of functionalized 3-alkyl substituents involves introduction of a nucleophilic carbon synthon by displacement of an a-substituent. This corresponds to formation of a benzylic bond but the ability of the indole ring to act as an electron donor strongly influences the reaction pattern. Under many conditions displacement takes place by an elimination-addition sequence[l]. Substituents that are normally poor leaving groups, e.g. alkoxy or dialkylamino, exhibit a convenient level of reactivity. Conversely, the 3-(halomethyl)indoles are too reactive to be synthetically useful unless stabilized by a ring EW substituent. 3-(Dimethylaminomethyl)indoles (gramine derivatives) prepared by Mannich reactions or the derived quaternary salts are often the preferred starting material for the nucleophilic substitution reactions. 

The tryptophan side-chain can also be introduced using methyl 2-ethoxy-1-nitroacrylate as an clcctrophile[l 7b]. Vinylation occurs at room temperature by addition elimination. Reduction by SnCl2 followed by acylation generates A -acyl-o(, 3-dehydrotryptophans. 

HydrOxy-THISs react with diethoxycarbonylazine producing a 1,2,4-triazole via addition, elimination of carbonyl sulfide (29). and subsequent loss of the ester groups (Scheme 20) (30). 

A number of compounds of the general type H2NZ react with aldehydes and ketones m a manner analogous to that of primary amines The carbonyl group (C=0) IS converted to C=NZ and a molecule of water is formed Table 17 4 presents exam pies of some of these reactions The mechanism by which each proceeds is similar to the nucleophilic addition-elimination mechanism described for the reaction of primary amines with aldehydes and ketones... 

The Addition-Elimination Mechanism of Nucleophilic Aromatic Substitution... 

THE ADDITION-ELIMINATION MECHANISM OF NUCLEOPHILIC AROMATIC SUBSTITUTION... 

The generally accepted mechanism for nucleophilic aromatic substitution m nitro substituted aryl halides illustrated for the reaction of p fluoromtrobenzene with sodium methoxide is outlined m Figure 23 3 It is a two step addition-elimination mechanism, m which addition of the nucleophile to the aryl halide is followed by elimination of the halide leaving group Figure 23 4 shows the structure of the key intermediate The mech anism is consistent with the following experimental observations... 

Write equations describing the addition-elimination mechanism for the reaction of hexafluorobenzene with sodium methoxide clearly showing the structure of the rate determining intermediate j... 

These results rule out substitution by addition-elimination because that mechanism requires the nucleophile to attach itself to the carbon from which the leaving group departs... 

Although nucleophilic aromatic substitution by the elimination-addition mecha nism IS most commonly seen with very strong amide bases it also occurs with bases such as hydroxide ion at high temperatures A labeling study revealed that hydroly SIS of chlorobenzene proceeds by way of a benzyne intermediate... 

Section 23 6 Nucleophilic aromatic substitutions of the type just shown follow an addition—elimination mechanism... 

Other aryl halides that give stabilized anions can undergo nucleophilic aromatic substitution by the addition-elimination mechanism Two exam pies are hexafluorobenzene and 2 chloropyridme... 

Nucleophilic aromatic substitution can also occur by an elimination-addition mechanism This pathway is followed when the nucleophile is an exceptionally strong base such as amide ion m the form of sodium amide (NaNH2) or potassium amide (KNH2) Benzyne and related arynes are intermediates m nucleophilic aromatic substitutions that pro ceed by the elimination-addition mechanism... 

Nucleophilic aromatic substitution by the elimination-addition mecha nism can lead to substitution on the same carbon that bore the leaving group or on an adjacent carbon... 

The product of this reaction as its sodium salt is called a Meisenheimer complex after the Ger man chemist Jacob Meisenheimer who reported on their formation and reactions in 1902 A Meisenheimer complex corresponds to the product of the nucleophilic addition stage in the addition-elimination mechanism for nucleophilic aromatic substitution... 

The reaction of benzenesulfomc acid with sodium hydroxide (first entry m Table 24 3) proceeds by the addition-elimination mechanism of nucleophilic aromatic substi... 

Addition-elimination mechanism (Section 23 6) Two stage mechanism for nucleophilic aromatic substitution In the addition stage the nucleophile adds to the carbon that bears... 

Cycloalkene (Section 5 1) A cyclic hydrocarbon characterized by a double bond between two of the nng carbons Cycloalkyne (Section 9 4) A cyclic hydrocarbon characterized by a tnple bond between two of the nng carbons Cyclohexadienyl anion (Section 23 6) The key intermediate in nucleophilic aromatic substitution by the addition-elimination mechanism It is represented by the general structure shown where Y is the nucleophile and X is the leaving group... 

Nucleophilic aromatic substitution (Chapter 23) A reaction m which a nucleophile replaces a leaving group as a sub stituent on an aromatic nng Substitution may proceed by an addition-elimination mechanism or an elimination-addition mechanism... 

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