Nitroalkanes sodium hydroxide

To a stirred mixture of 0.2 mol of the nitroalkane, 7.8 mL of EtOH and 0.39 mL of 10 N aq sodium hydroxide is added 0.2 mol of the freshly distilled aldehyde, with the temperature being maintained at 30 35 C. After approximately two thirds of the aldehyde has been added, an additional 0.39 mL of 10 N aq sodium hydroxide and 1.5 mL of water are added, then the aldehyde addition is continued. The mixture is stirred at 38 C for 65 h and is then treated with ca. 4 mL of 2 N aq hydrochloric acid to pH 7. It is extracted with hexane and the combined extract is washed with three 50-mL portions of water and sat. aq NaCl, dried over MgSOj and evaporated to give the crude nitroaldol which is purified by bulb-to-bulb distillation. 

The original procedure for the Nef reaction involved the aqueous sulfuric acid hydrolysis of the salts (170) obtained by the treatment of primary and secondary nitroalkanes with sodium hydroxide (equation 30). In contrast, if a neutral primary nitro derivative is treated in hot concentrated mineral acid, the corresponding carboxylic acid (172) is formed via the hydroxamic acid (171 equation 31). This reaction is known as the Meyer reaction and was first described in 1873. Protonation of salts of nitroalkanes occurs preferentially at the oxygen atom to give the aci form (173 equation 32). 

A kinetic study of the effect of water on the hydrolysis of (173) established the existence of two reaction pathways leading to the carbonyl derivatives, depending on water concentration. The unsatisfactory results observed in many instances led to modifications of the hydrolysis conditions. The supposed limitation of the Nef reaction due to steric hindrance is probably a result of the low solubility of nitroalkanes in aqueous alkali, as demonstrated by the success of the reaction if THF-H20," alcoholic sodium hydroxide" or alkoxide" is used. Silica gel" ° as a reaction medium is of great advantage when the use of organic solvents is undesirable. A two-layer method represents an improvement for the conversion of aromatic nitroalkanes. ... 

A huge acceleration of the Michael reaction of nitroalkanes with methyl vinyl ketone was mentioned when going from non-polar organic solvents to water. The hydrophobic effect could be at least to some extent involved, since additives, such as glucose or saccharose, accelerate the reaction even more [72]. Cetyltrimethylam-monium chloride as an amphiphilic species which can influence the hydrophobic interactions was found to promote the Michael reaction of various nitroalkanes with conjugated enones in dilute aqueous solutions of sodium hydroxide [73],... 

In general the reaction of nitroalkanes with aldehydes can be carried out by one of three processes 125 (1) Just sufficient alkali may be added to provide a sufficiently rapid reaction without dehydration or polymerization the reaction is slow and with the more complex reactants yields are also much lowered. (2) An equimolar amount of 10N-sodium hydroxide solution may be added at not more than 10°, but this method gives good yields only with nitromethane and straight-chain aldehydes and it fails with secondary nitroalkanes. (3) A solution of the aldehyde bisulfite compound may be treated with a warm solution of the sodium salt of the nitroalkane, primary nitro compounds then giving 70-80% yields. 

Many of the reactions involving a nitroalkane will proceed through the aci structure. Nitroalkanes react slowly with strong bases to form the nitronate salt. Nitromethane reaction with strong bases (e.g., sodium hydroxide) proceeds rapidly to form the sodium salt of methazonic aci. 

The first serious challenge to the single-step mechanism for the reaction for the nitroalkanes in water appeared in 2001 for the reaction of 1-(4-nitrophenyl)-ethane (NNPEh) with sodium hydroxide in water/acetonitrile (50 50 vol. %). The kinetics of the reaction (Scheme 1.16) were studied under pseudo-first-order conditions using stopped-flow spectrophotometry and the data were analyzed as IRC-time profiles. Rate constants and KIE were obtained by fitting experimental to calculated data for the reversible consecutive mechanism (Scheme 1.17) which is the simplest bimolecular mechanism. The theoretical data were obtained using the integrated rate law for that mechanism ignoring B as appropriate for pseudo-first-order conditions. 

Sodium hydroxide has been the most commonly used base in experimental nitroalkane proton transfer reaction studies.However, the computational studies of these reactions have generaUy been with hydroxide ion without the sodium counter ion. Recently a computational study of the proton transfer reactions of the three simple nitroalkanes in the presence of NaOH in water has been carried out and it was found that the presence of Na had an enormous effect on the energetics of the reactions. Double potential energy well diagrams, much like those found for the Sn2 reactions, were recorded for the proton transfer reactions of NM, NE and 2-NP with hydroxide ion in water. The computations included two explicit water molecules in the water cavity. The Gibbs free energies and enthalpies observed for the reactant complex (CPI), the TS and the product complex (CP2) both in the presence and absence of sodium ion and two explicit water molecules are summarized in Table 1.24. 

The most striking feature of the comparison of energies of structures and intermediates obtained from computations is the large difference in transition state Gibbs free energies and enthalpies in the presence and absence of the counter ion and two explicit water molecules. These differences are due to the large positive reaction entropies due to association of the Na and water molecules with the intermediates and transition states. Another importance conclusion that can be drawn is that the enthalpies of reaction are only mildly affected by the identity of the nitroalkane. The structures of intermediates and transition states for the reactions of the nitroalkanes with hydroxide ion in the presence of sodium ion in aqueous solution are illustrated in Scheme 1.18. 

Methylene compounds which contain only one electronegative group are normally inactive in telomerization. One exception is the nitroalkanes, which react very smoothly with butadiene [21, 22]. The telomerization of nitromethane in the presence of [PdCl2(PPh3)2] and sodium hydroxide at room temperature produces three nitro-compounds which are accompanied by a small amount of branched products (Equation 18). 

Another method for lengthening the carbohydrate chain is the addition of a nitroalkane to the aldehyde group. The nitroalkane is treated with sodium methox-ide to form a carbanion that adds to the aldehyde group to give a 1-nitro-l-deoxyalditol. The alditol can be converted into an aldehyde by treatment with sodium hydroxide, followed by acid this is the Nef reaction [41] (reaction 4.42). 

The original procedure for the bromination-oxidation-reduction route used bromine in aqueous potassium hydroxide, followed by oxidation with nitric acid-hydrogen peroxide and reduction with alkaline ethanol. This procedure was improved by using NBS in aqueous sodium bicarbonate for the initial oxime bromination, followed by oxidation with nitric acid and final reduction of the Q -bromonitroalkane with sodium borohydride in methanol. It is possible to convert oximes to nitroalkanes via this procedure without isolating or purifying any of the intermediates. This procedure is reported to give yields of between 10 and 55 % for a range of oxime to nitroalkane conversions. ... 

In the addition reaction, the used basic catalyst can be an alkali metal hydroxide, sodium carbonate and sodium alcohol. The addition reaction of multi-nitroalkane does not need a catalyst because it has a stable strong acidic anion. 

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