Carbanions nitrobenzenes

In contrast to the facile condensation of o-nitrotoluene with diethyl oxalate, other a-alky] nitrobenzenes are sluggish to react with diethyl oxalate or fail to react at all. It has been suggested that this is due both to steric and electronic factors effected by the alky] group, which destabilizes the methylene group in regard to formation of the carbanion. ... 

Carbanions of ct-chloroalkyl phenyl sulfones react with nitrobenzenes to effect tlirect nucleophilic replacement of hydrogens located on o and para to the nitro group fEq. 9.24. A very important feature is that VNS of hydrogen usually proceeds faster than conventional SnAt of halogen located In equally activated positions fEq. 9.25. The rule that VNS of... 

Typical VNS consists of a reaction between a nitroarene such as nitrobenzene and a carbanion containing a leaving group X at the carbanionic center. In the first step, addition of the carbanion to the nitroarene results in the formation of o-adduct, which undergoes P-elimination of HX to form the nitrobenzylic carbanion, which is subsequently protonated during the work-up procedure (Scheme 9.7). 

This reaction was found to be accelerated by the addition of electron acceptors such as nitrobenzene and m-trifluoromethylnitrobenzene. These electron acceptors accelerate the electron transfer from the carbanion to dioxygen. 

The ONSH reaction of the carbanion of 2-phenylpropionitrile (45 c) with nitrobenzene in liquid ammonia at -70 °C involves rate-limiting Carom—H bond breaking, as evidenced by the 9.8 times faster rate than for reaction of the analogous substitution of deuterium in 4-<7-nitrobenzene and perdeuterionitrobenzene. Reactions of the carbanion derived from (45c) with 4-chloro-3-trifluoromethylnitrobenzene and 4-chloronitrobenzene in toluene under phase transfer catalysis has also been studied." ... 

The oxidation of benzhydrol and 9-fluorenol in basic solution again shows a difference in regard to mechanism that can be primarily attributed to a difference in acidity as carbon acids. In tert-butyl alcohol benzhydrol enters into an oxidation scheme as the mono (oxy) anion. The data strongly suggest a free radical chain. Under these conditions the more acidic fluorenol or xanthenol oxidizes via carbanions or dianions. These oxidations can be catalyzed to occur via a free radical chain process by one-electron acceptors, such as nitrobenzene, and a free radical chain process may well be involved in the absence of the catalyst. 

The regioselective functionalization of nitrobenzene and benzonitrile derivatives has been performed via nucleophilic aromatic substitution of hydrogen by phosphorus-stabilized carbanions.41 Lithium phosphazenes have been found to be the most suitable nucleophiles for the substitution of hydrogen in nitrobenzene. This method represents a convenient alternative to the vicarious nucleophilic substitution for the synthesis of benzylic phosphorus derivatives using phosphorus-stabilized anions that do not bear a leaving group at the carbanionic centre. 

Isoxazole rings were annelated onto 5-nitroquinoline and isoquinoline-based o-nitrobenzyl-p-tolylsulfones by treatment with potassium phenoxide, which acted as both base and reductant (Equation (42)) <95H(40)187>. In the cases of quinolines as starting materials, product benzisoxazoles (75) both with and without phenoxy substitution were obtained, but in the case of an isoquinoline starting material no phenoxy-substituted product was generated. The reaction is thought to proceed via a nitrosobenzylsulfone carbanion intermediate, and can be applied to nitronaphthalenes but not to less active nitrobenzenes. 

Nucleophilic substitution of nitrobenzene with some carbanions was described in Chapter IV. 

Enolate anions from ketones, and carbanions from other compoimds containing activated hydrogen such as dimethyl sulphoxide and fluorene, can also donate one electron to suitable acceptors (e.g., nitrobenzene and phenylglyoxal) (Russell and Janzen, 1962 Russell et al., 1962 Russell et al., 1966a). One example is the generation of the p-nitrotoluene radical-anion fromp-nitrotoluene in base the formation... 

The SET reactions can be initiated by organic anions such as carbanions and heteroatom anions, reducing organic reagents such as tetrakis(N,N-dimethylamino)ethene, low valent metal, and electrochemical reduction. Irradiation by UV light is sometimes useful for the acceleration of SET reactions, but it is not necessarily required when good electron donors, for instance thiolates instead of thiols, are used. The chain reactions of, in particular, less reactive perfluoroalkyl bromides are inhibited by species such as nitrobenzene, para-dinitrobenzene, and hydroquinone [3,6]. The reactivity order of perfluoroalkyl hahdes... 

Draw resonance contributors for the carbanion that would be formed if meta-chloro-nitrobenzene could react with hydroxide ion. Why doesn t it react ... 

Cyclopropylphosphine oxides (140) react with the sodium salts of amides, presumably via cyclopropane ring-opening and intramolecular olefination, to give dihydropyrrole derivatives in moderate to good yield. Vicarious nucleophilic substitution reactions of a variety of substituted nitrobenzene derivatives with the carbanion of chloromethyldiphenylphosphine oxide to give o-(141) and p-(142)-nitrobenzyldiphenylphosphine oxides have been investigated. ... 

The effect of substituents on the rate of addition of carbanions to nitroarenes and the rate of p-elimination of HL from the o adducts have also been studied [8, 30, 31]. The former effect is an important parameter, because it is, in fact, a measure of influence of substituents on electrophilic activity of nitroaromatic rings. The effect of substituents on rate of the S Ar reactions of o- and p-halonitrobenzenes has been thoroughly studied [2, 32]. However, since the S Ar of halogen is a secondary process, the obtained data cannot be used as a real measure of electrophilicity of halonitroarenes. We have determined the effects of substituents and the ring structure on the rate of the VNS reactimi of nitroarenes with the carbanion of chloromethyl phenyl sulfone by using competitive experiments under the conditions, which assure a fast p-eUmination of HL from the o adducts [30, 31]. The values of VNS rates obtained under such conditions proved to correlate with those of the addition step. Selected values of the relative rate constants in relation to nitrobenzene as the standard are shown in Fig. 1. 

A serious limitation of VNS is connected with its mechanism, namely, conversion of intermediate ct adducts into the VNS products via bimolecular base-induced p-elimination. To cause the reaction, it is therefore necessary that these adducts be produced in a reasonable concentration. Indeed, low nucleophilic carbanions, such as dimethyl chloromalonate, do not react with moderately electrophilic nitrobenzene because of unfavorable equilibrium of the addition step, but react nicely with more electrophilic nitrothiazoles (Scheme 8) [34]. 

Equilibrium of the addition of nucleophiles to nitroarenes is a function of many factors, such as their nucleophilicity, electron deficiency of arenes, and their ability to stabilize adducts, as well as the reaction conditions. Thus, all these parameters are responsible for the feasibility of ONSH with nucleophiles sensitive to oxidation. Of substantial importance is temperature, since, due to the entropy factor, the equilibrium is shifted toward the adducts at a low temperature. For instance, addition of highly nucleophilic carbanion of 2-phenylpropionitrile to moderately active m-chloro nitrobenzene at —70°C in liquid ammonia or DMF/THF proceeds to completion, selectively in the para-position. Further oxidation of the formed adducts with... 

Arylsulfonylindazoles, novel S-HTe receptor antagonists, have been synthesized via the VNS reactions of para-substituted nitrobenzenes with carbanion of chloromethyl aryl sulfones followed by hydrogenation of the nitro group (Scheme 102). Further reaction of ortAo-aminobenzyl sulfones with sodium nitrite-acetic acid gave the desired 5-substituted indazoles of potential biological activity [237, 238]. 

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