Nitroalkanes carbon acidity

Nitroalkanes are acidic compounds the dissociation of a proton from a nitroalkane produces the nitroalkane anion, or nitronate, whose chemical and physical properties differ from those of the parent nitroalkane. The nitronate form of 2-nitropropane is more mutagenic in S. typhimurium TAIOO and TA 102 than is the neutral parent compound (Fiala et al., 1987b Dayal et al., 1989 Kohl et al., 1994), suggesting that propane 2-nitronate may act as an intennediate in the mechanism by w hich 2-nitropropane exerts its genotoxic and carcinogenic effects. This hypothesis is supported by studies indicating that both bacterial mutagenicity and induction of unscheduled DNA synthesis in rat hepatocytes are decreased by conditions (low pH or deuteration of the secondary carbon atom) that limit formation of the nitronate tautomer, and that the tautomerization of 2-nitropropane can be influenced by hepatic enzymes (Kohl et al., 1994). 

Nitroalkanes are relatively strong carbon acids, and deprotonation leads to the nitronate salt. The hydrolysis of this intermediate must take place in strong acid, to prevent the formation of side products such as oximes or hydroxynitroso compounds ... 

Acidity constants and rates of reversible deprotonation of triphenylphosphonium ion (54), (55) and pyridinium ions (56), (57) by amines in water, 50 50 v/v DMSO-water, and 90 10 v/v DMSO-water have been determined.157 The intrinsic rate constants for proton transfer were relatively high for all four carbon acids and showed little solvent dependence. This is in contrast with nitroalkanes, which have much lower intrinsic rate constants and show a strong solvent dependence.158... 

Nitro = ac/-nitro tautomerism occupies a special role as it has been speculated to occur under conditions where high energy explosives detonate. It has been proposed as one of the important initial steps responsible for the cascade of reactions leading to the high energy release during detonation [1], Nitro = aci-nitro tautomerism in nitro compounds RjCH-NO leads to nitronic acids, R2C=N(0)OH. Kinetic studies show similar pKa values for nitronic acids and their carbon counterparts, the carboxylic acids [1]. Nitroalkane = nitronic acid tautomerism has been assumed not to be an acid-catalyzed process because of the poor basicity of N02 group [4]. However, recent work by Erden et al. showed that this tautomerism can, in fact, be achieved under acid catalyzed... 

The third category of carbon acid substrates is nitroalkanes that readily dissociate to resonance-stabilized carbanions. The carbanions cannot be oxidized by loss of two electrons because of the instability of the resultant carbonium ion. Oxidation of nitroalkanes occurs through loss of nitrite ion. 

The reaction of nitroalkanes with methoxymagnesium methyl carbonate represents an acylation by carbonic acid it affords good yields of <%-nitro carboxylic acids by way of a chelate-like intermediate 433... 

The experimental verification of Westheimer s theory has been studied for the last decade or so and the explanation is now believed to be valid. More O Ferrall [14] collected data for the value of k /k for the ionisation of ketones and nitroalkanes he showed that at ApK = 0 (where the pA of the attacking base equals that of the carbon acid) there is a maximum isotope effect. The transition state has a good chance of being symmetrical thus yielding a large isotope effect at ApK = 0 where the energy of reactant is the same as that of product. Work from the laboratories of Kresge [15] and Jencks [16] confirms these notions for the case of heteroatoms (Fig. 5). 

Thus, nitroalkanes are more effective agents than diethylmalonate in effecting the macrocyclisation given above. It is quite possible that carbon acids with higher p.Ka values than C2H5NO2, for example (C2H500C)2CH2, in non-aqueous conditions would be more effective. 

The reaction of / -dinitrobenzene with carbon acids in liquid ammonia in the presence of potassium f-butoxide [232] gives substituted products such as (87), and reaction with carbanions daived from nitroalkanes in DMSO [233] may also result in substitution to give products such as (82). 

Carbon acids studied with respect to Br nsted relations include carbonyl compounds, nitroalkanes, sulfones and nitriles(2,9). Among the carbon acids the conjugated hydrocarbons constitute a unique class. They cover a broad range of pK values and the relative acidities depend almost wholly on delocalization of charge in the corresponding carbanions. For example. Table II summarizes the pKcsCHA of a number of hyrdrocarbons whose carbanions are... 

DMSO, at 20 This ketone is complicated by having a significant hydrate content ( h = 0.044), and forms its hydrate anion at high pH. The compound is very acidic (p STa = 11.18 at 25 °C), and its log ko value of 0.92 is lower than that of any sterically unhindered carbon acid (except those of nitroalkanes). Rate constants for deprotonation by hydroxide are also reported, and discrepancies in the results of Frey are put down to, in the main, an incomplete kinetic treatment of their raw data. The results are discussed in the context of Kresge s rate-equilibrium correlation for simple ketones and aldehydes. ... 

Nitroparaffias (or nitroaLkanes) are derivatives of the alkanes ia which one hydrogen or more is replaced by the electronegative nitro group, which is attached to carbon through nitrogen. The nitroparaffins are isomeric with alkyl nitrites, RONO, which are esters of nitrous acid. The nitro group ia a nitroparaffin has been shown to be symmetrical about the R—N bond axis, and may be represented as a resonance hybrid ... 

Barton and co workers have explored the aryladon of various nucleophiles inclndmg nitroalkanes using bismuth reagents Reacdon of 2-nitropropane v/ith triphenylbismnth carbonate gives 2-nitro-2-phenylpropane in 80% yield Recently, this aryladon has been used for the synthesis of unusual amino acids Aryladon of ct-nitro esters v/ith triphenylbismnth dichloride followed by redncdon gives unique ct-amino acids fEq 5 68 ... 

Scheme 2.23 provides some examples of conjugate addition reactions. Entry 1 illustrates the tendency for reaction to proceed through the more stable enolate. Entries 2 to 5 are typical examples of addition of doubly stabilized enolates to electrophilic alkenes. Entries 6 to 8 are cases of addition of nitroalkanes. Nitroalkanes are comparable in acidity to (i-ketocslcrs (see Table 1.1) and are often excellent nucleophiles for conjugate addition. Note that in Entry 8 fluoride ion is used as the base. Entry 9 is a case of adding a zinc enolate (Reformatsky reagent) to a nitroalkene. Entry 10 shows an enamine as the carbon nucleophile. All of these reactions were done under equilibrating conditions. 

The carboxylation of nitroalkanes with magnesium methyl carbonate followed by esterification gives a-nitro esters in 40-58% yield.14 Magnesium methyl carbonate is prepared by the saturation of a magnesium methoxide suspension in DMF with C02. More elegantly, sodium salt of nitroalkanes can he carboxylated by means of 1 -ethoxycarbonylbenzotriazole to give a-nitro esters in 55-80% yield (Eq. 5.7).15 Nitroacetic acids and its esters can serve as useful... 

The most characteristic reaction of butadiene catalyzed by palladium catalysts is the dimerization with incorporation of various nucleophiles [Eq. (11)]. The main product of this telomerization reaction is the 8-substituted 1,6-octadiene, 17. Also, 3-substituted 1,7-octadiene, 18, is formed as a minor product. So far, the following nucleophiles are known to react with butadiene to form corresponding telomers water, carboxylic acids, primary and secondary alcohols, phenols, ammonia, primary and secondary amines, enamines, active methylene compounds activated by two electron-attracting groups, and nitroalkanes. Some of these nucleophiles are known to react oxidatively with simple olefins in the presence of Pd2+ salts. Carbon monoxide and hydrosilanes also take part in the telomerization. The telomerization reactions are surveyed based on the classification by the nucleophiles. 

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