Alkoxides aromatic nucleophilic substitution

Treatment with base (NaH can be used) now converts the OH group into an alkoxide and it does the next aromatic nucleophilic substitution. In this reaction we are attacking the position metato the ketone so we cannot put the negative charge on the oxygen atom. The remaining three fluorines must stabilize it by the inductive effect we described earlier. 

In water, N3 is much less reactive in aromatic nucleophilic substitution than expected from its reactivity toward carbocations, that is, its N+value. Ritchie (43) initially developed his N+ scale from nucleophilicities toward preformed carbocations and the scale fits the data for nucleophilicities toward many electrophiles, regardless of their charge. However, in water, and similar hydroxy lie solvents, the nucleophilicity of azide ion, relative to that of other anions, seems to be related to the carbocation-like character of the electrophile. An acyl derivative with its sp2 carbonyl group is somewhat akin to a carbocation stabilized by an alkoxide group, >C=0 <-— >C+-0 , just as a triarylmethyl carbocation is stabilized by electron delocalization into the aryl groups and azide ion is a good nucleophile toward these electrophiles. As compared with anions such as OH- or CN , azide ion, in water, is very reactive toward carbocations and in deacylation but is relatively unreactive toward dinitrohaloarenes (44). 

An efficient method for an aromatic nucleophilic-substitution reaction using a solid-liquid transfer catalysis coupled with MWI was applied to the reaction of halogenopyridine 168 with alkoxides or phenoxides in the presence of 18-crown-6 as... 

There have been a large number of detailed studies, especially involving kinetic measurements, that have helped to determine the reactivity of various nucleophiles, solvent effects, and the finer details of aromatic nucleophilic substitutions proceeding via the addition-elimination mechanism. We will not attempt to summarize these results here, since reviews are available. Carbanions, alkoxides, and amines are all reactive in nucleophflic aromatic substitution and provide most of the cases in which this reaction has been used preparatively. Some examples are given in Scheme 7.7. 

Meisenheimer complexes, the stable intermediates in aromatic nucleophilic substitution reactions, are of interest since there is speculation as to whether the attack of an alkoxide ion on nitroaryl compounds results in a covalent species, or alternatively in a charge-transfer complex. The analysis of one such intermediate, the potassium methoxide adduct of 4-methoxy-5,7-dinitrobenzfurazan (89), confirms that in this case the alkoxide moiety... 

Bromo-N-alkylnaphthalimides undergo aromatic nucleophilic substitution reaction with amines, alkoxides and thiols under microwave irradiation in the presence of KF/AI2O3 under solvent-free conditions to afford a number of fluorescent 4-sub-stituted-l,8-naphthalimide dyes. This is an efficient method for C-N, C-0 and C-S bond formation by applying suitable nucleophiles. Adducts were produced in good to excellent yields (70-95%) and relatively in short times (Bardajee, 2013). 

Nucleophilic Substitutions of Benzene Derivatives. Benzene itself does not normally react with nucleophiles such as haUde ions, cyanide, hydroxide, or alkoxides (7). However, aromatic rings containing one or more electron-withdrawing groups, usually halogen, react with nucleophiles to give substitution products. An example of this type of reaction is the industrial conversion of chlorobenzene to phenol with sodium hydroxide at 400°C (8). 

Although chlorobenzene is rather inactive in usual reactions, its activity is enhanced by complex formation, and two products are formed by the reaction of stabilized carbanions on the complexed chlorobenzene 207, depending on the conditions [44], The anion of a-methy l propionitrile reacts at the meta position at —78 °C, and the mete-substituted product 208 is obtained by oxidation with I2. However, equilibration (rearrangement) of the carbanion occurs at 25 °C, because the attack of the carbanion is reversible, and the substitution product 209 of the chlorine is obtained. The fluorobenene 210, coordinated by Cr(CO)3, is very reactive. Reaction of y-butyrolactone to the o-lithiated fluorobenzene 211 gives rise to the alkoxide 212, which displaces the fluoride intramolecularly to give the cyclic ether 213 [52], In other words, the complex 211 can be regarded as the 1,2-dipolar synthon 214. However, Cr(CO)3-complexed aromatic bromide and iodide can not be used for the nucleophilic substitution. 

The carbonyl group at G-4 of the 3-aryl-4-benzoylazetidin-2-one is reduced with sodium borohydride to the corresponding hydroxyl group <2003T5259>. Treatment of azetidin-2-one 372 with sodium hydride gave a fused tricyclic azetidin-2-one 373 (Equation 140) as a result of an intramolecular nucleophilic substitution reaction of the alkoxide with an aromatic group at the C-3 position. 

Nuclear and side chain substitution in aromatics or substitution of a -hydrogen in alkylamines is — in most cases — best rationalized by postulating radical cations as intermediates. For anodic nuclear substitution of aromatics, especially for acyloxylation, cyanation or bromination a ECnECb3 -mechanism is assumed 37,4 9,50,226,227). jc-oxidation of the aromatic to the radical cation 28, which reacts with a nucleophile Nu, e.g., acetate, cyanide, alkoxide, followed by a second electron transfer and deprotonation (Eq. (98) ) ... 

While the major use for palladium catalysis is to make carbon-carbon bonds, which are difficult to make using conventional reactions, the success of this approach has recently led to its application to forming carbon-heteroatom bonds as well. The Overall result is a nucleophilic substitution at a vinylic or aromatic centre, which would not normally be possible. A range of aromatic amines can be prepared direcdy from the corresponding bromides, iodides, or triflates and the required amine in the presence of palladium(O) and a strong alkoxide base. Similarly, lithium thiolates couple with vinylic triflates to give vinyl sulfides provided lithium chloride is present. 

Complexing with chromium tricarbonyl provided activation of the aromatic ring for nucleophilic substitution of a fluorine atom with j6-amino-alkoxides and then for rearrangements of the initially formed products. Thus,... 

Uncatalyzed nucleophilic substitution reactions of Grignard reagents with aromatic compounds is much more difficult than with alkyl species, unless the leaving group (sometimes halide usually alkoxide is preferred) is activated by one or more potent electron-withdrawing substituents, such as an oxazoline, nitro, or ester moiety, most often at the ortho... 

The displacement of nucleofugal groups is usually realized through the addition-elimination two-step mechanism Sn(AE) . For instance, the trichloromethyl group in 1,2,4-triazines is displaced easily by the action of hydrazine, butylamine, sodium hydroxide, and alkoxides (Scheme 81) <2004SOS(17)357> however, in the reaction of 6-aryl-3-trichloromethyl-l,2,4-triazines with aromatic C-nucleophiles, substitution of hydrogen takes place <2004RCB1295>. 

Aniline reacts with nitrous acid to give benzenediazonium salts, which react with a variety of reagents via a substitution reaction. These reagents include cuprous salts, aqueous acid, iodide, hypophosphorous acid, and activated benzene derivatives. Nucleophilic substitution at the sp carbon of a halo-benzene derivative does not occur unless high heat and pressure are used. Electron-withdrawing substituents on the benzene ring significantly lower the temperature required for the reaction. Nucleophiles for this nucleophilic aromatic substitution reaction include water, hydroxide, alkoxide, and amines. 

---