Aromatic halides reactions with ketones

Aromatic halides react with crown ether-complexed K02 by an electron-transfer mechanism and not by nucleophilic attack, as was shown by Frimer and Rosenthal (1976) using esr spectroscopy. The corresponding phenol is the main reaction product (Yamaguchi and Van der Plas, 1977). Esters are saponified by the K02/18-crown-6 complex in benzene, presumably by an addition-elimination pathway (San Fillippo et al., 1976). The same complex has been used to cleave cr-keto-, or-hydroxy-, and or-halo-ketones, -esters, and -carboxylic acids into the corresponding carboxylic acids in synthetically useful quantities (San Fillippo et al., 1976). 

Lithiated indoles can be alkylated with primary or allylic halides and they react with aldehydes and ketones by addition to give hydroxyalkyl derivatives. Table 10.1 gives some examples of such reactions. Entry 13 is an example of a reaction with ethylene oxide which introduces a 2-(2-hydroxyethyl) substituent. Entries 14 and 15 illustrate cases of addition to aromatic ketones in which dehydration occurs during the course of the reaction. It is likely that this process occurs through intramolecular transfer of the phenylsulfonyl group. 

Appaiendy a molai equivalent of catalyst (AlCl ) combines with the acyl halide, giving a 1 1 addition compound, which then acts as the active acylating agent. Reaction with aromatics gives the AlCl complex of the product ketone hberating HX ... 

Wipf has shown that this method is quite general and tolerates several functional groups, such as ethers, thioethers, silanes, halides, aromatic rings, and olefins. The iodoalkyne 64 is readily carbometalated and after treatment with the dialkynylcuprate 59 furnishes the functionalized copper reagent 65, which smoothly undergoes 1,4-addition reactions with enones. Thus, in the case of 2-cyclohexenone, the functionalized ketone 66 is produced in 85% yield (Scheme... 

Electrochemical studies are usually performed with compounds which are reactive at potentials within the potential window of the chosen medium i.e. a system is selected so that the compound can be reduced at potentials where the electrolyte, solvent and electrode are inert. The reactions described here are distinctive in that they occur at very negative potentials at the limit of the cathodic potential window . We have focused here on preparative reductions at mercury cathodes in media containing tetraalkylammonium (TAA+) electrolytes. Using these conditions the cathodic reduction of functional groups which are electroinactive within the accessible potential window has been achieved and several simple, but selective organic syntheses were performed. Quite a number of functional groups are reduced at this limit of the cathodic potential window . They include a variety of benzenoid aromatic compounds, heteroaromatics, alkynes, 1,3-dienes, certain alkyl halides, and aliphatic ketones. It seems likely that the list will be increased to include examples of other aliphatic functional groups. 

The reaction of aryl and hetaryl halides with ketone enolate ions can also be initiated by sodium amalgam in liquid ammonia. In these reaction conditions, neither the carbonyl group nor the aromatic moiety are reduced, as was the case in the reaction initiated with solvated electrons. Thus, the ketones below have been synthesized, mostly in good yields175. 

A typical reaction is the photostimulated substitution of aryl halides by ketone [121-131] (and much less efficiently aldehyde [124]) enolate anions (Scheme 5), both inter- [121-128] and intramolecularly [129-131]. The SRN1 reaction with o-bromoacetophenones is a useful method for the construction of an aromatic ring (Scheme 24) [132-133], with o-halophenylalkyl ketones for macrocycles (Scheme 25) [134], with o-haloanilines for indoles [123], with o-halobenzylamines for isoquinolines [135], and several other heterocyclic syntheses are possible [136]. 

Alkylahn of ketones. Ketones are readily alkylated in the z-position on reaction with alkyl halides in the presence of 50% aqueous sodium hydroxide and catalytic amounts of bcnzyltricthylammonium chloride. The catalytic effect of the salt if particularly marked in the case of weakly active alkyl halides. Thus the reaction o phenylacctone with n-butyl bromide in the ab.sence of catalyst gives 3-phenyl-2-heptanonc in 5% yield the yield is 90% in the presence of Ihe catalyst. Highest yields are obtained with ketones bearing an aromatic substituent at the Z-CH2 group. 

The SET ability of alkali metals may be improved by the presence of aromatic compounds such as naphthalene or its derivatives. Thus a number of desulfurizations of sulfides - or dithioke-tals have been performed (generally at low temperature in order to diminish side reactions) with Li in the presence of a catalytic amount of naphthalene, or with an excess of lithium naphthalenide or lithium l-(dimethylamino)naphthalenide (LDMAN Scheme 11). Note that 1-dimethylaminonaph-thalene may be easily removed from the reaction product during the work-up. These desulfurizations tolerate ethers and nitriles but do not respect halides, ketones, esters and a few other structures. ... 

The hydrated electron may be visualized as a localized electron surrounded by oriented water molecules. As mentioned earlier, it reacts by adding into a vacant orbital on the acceptor molecule or ion (Eq. 2). Rate constants for this reaction range from 19 dm mol s for S = H2O up to the diffusion-controlled limit, but the activation energy is invariably small (6-30 kJ mol" ) this indicates that the entropy of activation is the dominant kinetic parameter. This can be understood in terms of the accessibility to the electron of a vacant orbital on S. Molecules such as water, simple alcohols, ethers, and amines have no low-lying empty orbitals to accommodate an extra electron this explains why solvated electrons have an appreciable lifetime in these solvents. On the other hand, eaq reacts rapidly with organic compounds with low-lying vacant orbitals, for example, most aromatics, halides, aldehydes, ketones, thiols, disulfides, and nitro compounds. 

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