Toward electrophilic reagents

As discussed in Section 4.01.5.2, hydroxyl derivatives of azoles (e.g. 463, 465, 467) are tautomeric with either or both of (i) aromatic carbonyl forms (e.g. 464,468) (as in pyridones), and (ii) alternative non-aromatic carbonyl forms (e.g. 466, 469). In the hydroxy enolic form (e.g. 463, 465, 467) the reactivity of these compounds toward electrophilic reagents is greater than that of the parent heterocycles these are analogs of phenol. 

Figure 30 Indazole reactivity towards electrophilic reagents...

Reactions of alkynes with electrophiles are generally similar to those of alkenes. Because the HOMO of alkynes (acetylenes) is also of n type, it is not surprising that there IS a good deal of similarity between alkenes and alkynes in their reactivity toward electrophilic reagents. The fundamental questions about additions to alkynes include the following. How reactive are alkynes in comparison with alkenes What is the stereochemistry of additions to alkynes And what is the regiochemistry of additions to alkynes The important role of halonium ions and mercurinium ions in addition reactions of alkenes raises the question of whether similar species can be involved with alkynes, where the ring would have to include a double bond ... 

The numerical value of hardness obtained by MNDO-level calculations correlates with the stability of aromatic compounds. The correlation can be extended to a wider range of compounds, including heterocyclic compounds, when hardness is determined experimentally on the basis of molar reffactivity. The relatively large HOMO-LUMO gap also indicates the absence of relatively high-energy, reactive electrons, in agreement with the reduced reactivity of aromatic compounds toward electrophilic reagents. 

In carbohydrates in which benzyl groups are used extensively for protection, the stability of the benzyl groups toward electrophilic reagents is increased by the presence of electron-withdrawing groups in the ring." ... 

The reaction of benzylmagnesium chlorides wnth thiophenealde-hydes and thienyl ketones has been used for the preparation of styrylthiophenes and 1,2,2-triarylethylenes, which are of biological interest. In stilbene and 1,2,2-triphenylethylene the reactivity toward electrophilic reagents is transferred with deactivation to the double bond. However, styrylthiophene is formylated and acylated... 

The cyclic diazo compounds (diazirines 65) are very unreactive compounds. Specially noticeable is the absence of the reactivity toward electrophilic reagents which is characteristic of the linear isomers. Acids or aldehydes which react smoothly with the aliphatic diazo compounds are without action on the cyclic diazo compounds. Iodine does not attack the cyclic diazo compounds. 

Physical properties are similar to alkanes and the chemistry is dictated by the carbon triple bond. This bond is less reactive than the olefin double bond towards electrophilic reagents, but more... 

The difluorocarbene complex 5 reacts rapidly with nucleophiles but is completely unreactive toward electrophilic reagents (22), e.g.,... 

Metalated cyclic aldo-nitrones are characterized by high reactivity toward electrophilic reagents. Reactions with aldehydes and ketones afford satisfactory yields of a-hydroxymethyl substituted derivatives of nitrones (551). The reactions were also carried out with a number of aliphatic, aromatic, and hetero-aromatic aldehydes and ketones (Schemes 2.124 and 2.125). 

Quinoline is much more reactive towards electrophilic substitution than pyridine, but this is because substitution occurs on the benzene ring, not on the pyridine. We have already seen that pyridine carbons are unreactive towards electrophilic reagents, with strongly acidic systems protonating the nitrogen... 

The 2,5-, 2,3- and 3,4-dihydropyridines have received very little study regarding their reactivity toward electrophilic reagents. This is undoubtedly due to their instability and the low number of authentic derivatives that are known. 

The exceedingly high reactivity of ferrocene to Friedel-Crafts acylation is exemplified by the fact that mild catalysts such as stannic chloride (63), boron trifluoride (32), zinc chloride (86), and phosphoric acid (29), can be used with considerable success. When ferrocene and anisole were allowed to compete for limited amounts of acetyl chloride and aluminum chloride, acetylferrocene was the sole product isolated, again illustrating the high reactivity of ferrocene toward electrophilic reagents (6). 

The great reactivity of ferrocene toward electrophilic reagents prompted an early examination of its behavior with aryldiazonium salts. Azoferrocenes were expected to be formed by analogy to the reaction of phenol and related reactive aromatic compounds. The reactions instead were found to proceed with elimination of nitrogen and the products were arylferrocenes (XXIII). 

The behavior of organolithium-diazine adducts toward electrophilic reagents, such as methyl iodide, methyl chloroformate, and tosyl chloride, has also been investigated.149... 

In Section 10-5 we showed that ethyne is much less reactive toward chlorine than is ethene. The same is true for hydrogen chloride. Flowever, when hydrogen chloride adds to 3-butenyne, it adds to the triple bond instead of the double bond, thereby forming 2-chloro-1,3-butadiene instead of 3-chloro-1-butyne. With reference to the discussion in Section 13-2, explain why the order of reactivity of the double and triple bonds of 3-butenyne toward electrophilic reagents may be different from that of ethene and ethyne ... 

All are exceptionally reactive towards electrophilic reagents, particularly in alkaline solution, and all are readily oxidized. The 1,2- and 1,4-benzenediols, but not 1,3-benzenediol, are oxidized to quinones ... 

Erlenmeyer was first to consider ends as hypothetical primary intermediates in a paper published in 1880 on the dehydration of glycols.1 Ketones are inert towards electrophilic reagents, in contrast to their highly reactive end tautomers. However, the equilibrium concentrations of simple ends are generally quite low. That of 2-propenol, for example, amounts to only a few parts per billion in aqueous solutions of acetone. Nevertheless, many important reactions of ketones proceed via the more reactive ends, and enolization is then generally rate-determining. Such a mechanism was put forth in 1905 by Lapworth,2 who showed that the bromination rate of acetone in aqueous acid was independent of bromine concentration and concluded that the reaction is initiated by acid-catalyzed enolization, followed by fast trapping of the end by bromine (Scheme 1). This was the first time that a mechanistic hypothesis was put forth on the basis of an observed rate law. More recent work... 

THE EFFECT OF THE METAL ATOM IN SUBSTRATES R M ON THE REACTIVITY OF THE SUBSTRATE TOWARDS ELECTROPHILIC REAGENTS... 

Condensed aromatic hydrocarbons are more reactive towards electrophilic reagents, and naphthalene, for example, may be brominated quite readily in solution in carbon tetrachloride without the need for a catalyst electrophilic attack takes place at the more reactive a-position to yield 1-bromonaphthalene (Expt 6.25). 

In the molecule of internal olefin F-butene-2, the inductive and resonance effects of CF3 and F substituents compensate for each other due to symmetry of the molecule. As a result of the much lower polarization of the C=C bond (along with steric shielding of it by a bulky CF3 group), it is responsible for the significantly lower reactivity of this olefin towards electrophilic reagents ... 

Benzoselenophene is generally more reactive toward electrophilic reagents, although, like 1-benzothiophene, it undergoes mainly p-substitution (Scheme 5). 

Tetrazoles exhibit qualities of acids, bases, acceptors of hydrogen bonds (cf. Section 6.07.4.5), and polydentate ligands (cf. Section 6.07.5.3.4). NH-LJnsubstituted tetrazoles behave both as substrates and intermediates in transacylation processes (cf. Section 6.07.5.4), etc. Tetrazolate anions (tetrazolides) possess high aromaticity and reactivity toward electrophilic reagents (cf. Sections 6.07.4.1 and 6.07.5.3.2). The thermal and photochemical decomposition of tetrazoles involves formation of nitrenes and other intermediates of high reactivity (cf. Sections 6.07.5.2 and 6.07.5.7) These properties provide a possibility of use tetrazoles as catalysts in chemical and biochemical reactions. 

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