Electrophilic Hydrogen Exchange

Addition of Grignard reagents and organolithium compounds to the pyridazine ring proceeds as a nucleophilic attack at one of the electron-deficient positions to give initially 

4- addition products which rearrange to 1,2-dihydro products. 3-Methoxy-6-phenyl-pyridazine reacts with t-butylmagnesium chloride to give 4-t-butyI-3-methoxy-6-phenyl- 

5- double bond of 3,6-dimethoxypyridazine to give 4-substituted 4,5-dihydropyridazine derivatives. 

Phenyllithium in ether adds to pyridazine and 6-substituted pyridazines at position 3. By using TMEDA, addition at position 4 is strongly promoted (78RTC116). 

The addition of phenyllithium to 6-arylpyridazin-3(2Er)-one takes place at position 6 to give 6-aryl-3-oxo-6-phenyl-l,2,3,4-tetrahydropyridazine and the reaction of 6-aryl-2,4-diphenylpyridazin-3(2H)-one with phenyllithium or phenylmagnesium bromide affords 6-aryl-2,3,4,6-pentaphenyl-l,2,3,4-tetrahydropyridazine (80S457). 

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C. Application of the Principle of Additivity of Free Energies of Activation to Reactions Involving Protophilic and Electrophilic Hydrogen Exchange... 

Electrophilic hydrogen exchange in deuterioselenophenes was studied using a 4 1 mixture of acetic and trifluoroacetic acids.79 Rate constants and partial rate factors were determined for the deuterium replacement at 25°C (see Table IV). Rate constants were calculated... 

This genera] scheme could be used to explain hydrogen exchange in the 5-position, providing a new alternative for the reaction (466). This leads us also to ask whether some reactions described as typically electrophilic cannot also be rationalized by a preliminary hydration of the C2=N bond. The nitration reaction of 2-dialkylaminothiazoles could occur, for example, on the enamine-like intermediate (229) (Scheme 141). This scheme would explain why alkyl groups on the exocyclic nitrogen may drastically change the reaction pathway (see Section rV.l.A). Kinetic studies and careful analysis of by-products would enable a check of this hypothesis. 

Hydrogen exchange, in thiazole, especially deuteration, has been quantitatively investigated (379,380), but the mechanism of the reaction carried out at acidic or neutral pH corresponds to a protonation-deprotonation process (380), different from electrophilic substitution and is discussed in section I.3.E. 

Electrophilic Attack. A variety of boranes, heteroboranes, and metaHaboranes undergo electrophilic substitution. SusceptibiUty of boranes to electrophilic attack is often detected by deuteron—proton exchange experiments. Eor example, electrophilic hydrogen—deuterium exchange of occurs at the l-,2-,3-, and 4-positions when exposed to DCl in the presence of AlCl (81). The trend to increasing positive sites in is... 

Electrophilic aromatic hydrogen exchange reactions fall into two classes, namely those reactions catalysed by acid and those reactions catalysed by base. Of these the former are by far the most common and have been subjected to the most extensive and intensive kinetic studies. 

Kinetic studies of substituent effects in electrophilic aromatic hydrogen exchange... 

The advantages of the hydrogen exchange as a model electrophilic aromatic substitution are now well recognised and have been emphasised504, 522, 523, so that a very considerable body of data is now to be found in the literature. In order to simplify presentation of this, the data are considered under headings of the acid medium employed for the studies. 

In Volume 13 reactions of aromatic compounds, excluding homolytic processes due to attack of atoms and radicals (treated in a later volume), are covered. The first chapter on electrophilic substitution (nitration, sulphonation, halogenation, hydrogen exchange, etc.) constitutes the bulk of the text, and in the other two chapters nucleophilic substitution and rearrangement reactions are considered. 

Hydrogen as the Leaving Group in Simple Substitution Reactions A. Hydrogen as the Electrophile 11-1 Hydrogen Exchange Deuterio-de-hydrogenation or deuteriation... 

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