Nitroalkanes

Nitroalkanes. A process was developed and operated for a time for the manufacture of s-caprolactam based on the nitration of cyclohexane.197 Nitrocyclohexane thus prepared was transformed to e-caprolactam via cyclohexanone oxime. At present the only industrial process to produce nitroalkanes by direct nitration is the manufacture of nitromethane, nitroethane, 1-nitropropane, and 2-nitropropane. 

All four compounds are produced by the vapor-phase nitration of propane.197-199 Nitroalkanes are important as solvents and intermediates.199 

The nitration of propane is operated at 370-450 C and at about 10 atm. The use of about a fourfold excess of propane, 60-70% nitric acid, and short residence time ensures good temperature control.199 The conversion of nitric acid to nitroalkanes is less than 50% (the balance are nitrogen oxides). Excess propane is usually recycled to achieve about 60-80% yield of nitroalkanes. Under these conditions nitropro-panes are the main products. 

Considering the ample possibilities to generate new carbon-hereoatom bonds, particularly the wide range of oxygenation reactions, only limited attempts have been made to carry out direct amination of hydrocarbons. A few examples of animation of alkanes, alkenes, and aromatics are discussed briefly here. 

Amination of alkanes (cyclohexane, heptane, adamantane) was achieved with iron and manganese porphyrin catalysts by tosylimidoiodobenzene to yield tosyl-amino derivatives.200 Selective 1-substitution of adamantane (56% yield) and 2-substitution of heptane (66% selectivity) were reported. 

In nitroalkanes, a hydrogens, those hydrogen atoms that are attached to the same carbon atom to which the nitro group is attached, have a characteristically large chemical shift. 

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162 Nuclear Magnetic Resonance Spectroscopy Part One Basic Concepts 

Build models of these three compounds and then explain why the two circled methyl groups have such small chemical shifts. 

one can inspect the spectrum and visually approximate the relative numbers of protons, thus avoiding the mathematical approach shown in the table. Using this eyeball approach, you can determine that the second spectrum (17b) yields a ratio of 1 3 6 = 10 H. 

Few nitroalkanes have found use as explosives. Nitromethane (CH3NO2) is a notable exception, and there have been numerous studies of its decomposition pathway [42,43,44]. It has been reported that nitromethane is sensitized to detonation by acidic and basic media. This sensitizing effect is approximately linear with the pKa [45], The best explanation of the effect is that nitromethane undergoes autocatalytic decomposition by an ionic mechanism under acidic or basic conditions [46,47], Among other mononitroalkanes, nitroethane, the nitropropanes, and chloropicrin C13C(N02), have been the most extensively studied. The decomposition 

Shaw calculated the isokinetic point between homolysis and elimination as 770K for mononitro- and vicinal dinitro-alkanes and as 370K for gem-dinitro species [51]. In gem-polynitro species the C-N02 bond is weaker than in mononitro compounds due to inductive effects [52] thus, homolysis is thought to be the principal decomposition pathway in 2,2 dinitropropane and hexanitroethane [48]. Octanitrocubane has recently been synthesized (Fig. 6). Its crystal density was lower (1.979 g/cm3) than the predicted 2.1 [53]. Like hexanitrobenzene, octanitrocubane has a perfect oxygen balance, but at this point it appears unlikely that further development of this compound will be undertaken. 

The reducdon of nltroalkenes v/ith ZnBHl in 1,2-dimethoxyethane (DMEi gives the corresponding oximes or nitroalkanes depending on the stnicture of nltroalkenes. ct-Subsdtuted nltroalkenes are reduced to the oximes, whereas those having no ct-subsdtuents afford the nitroalkanes fEq. 3.47.  

Vetyselecdve reducdon of nltroalkenes into the corresponding nitroalkanes is achieved using NaCNBH- in the presence of the zeolite H-ZSM 5 in methanol fEq. 3.48.  

Additional examples of the synthetic utility of this procedure are demonstrated in Eqs 3 50-3 53 The nitro and nitroalkyl groups in the products are Further converted into various Functional groups such as carbonyl, amino, and alkyl groups This is discussed in Chapter 6 

These contain C-NO2 bonds in contrast to the nitrate esters of, for example, glycerol and pentae-rythritol with O-NO2 bonds. Nitroalkanes have been used as solvents, and there are a few naturally occurring nitroalkanes such as the glycoside of the toxic 3-nitropropionic acid and the 0-methyl 

The enantiomeric reduction of 2-nitro-l-phenylprop-l-ene has been studied in a range of Gram-positive organisms including strains of Rhodococcus rhodochrous (Sakai et al. 1985). The enantiomeric purity of the product depended on the strain used, the length of cultivation, and the maintenance of a low pH that is consistent with the later results of Meah and Massey (2000). It has been shown that an NADPH-linked reduction of a,p-unsaturated nitro compounds may also be accomplished by old yellow enzyme via the flcf-nitro form (Meah and Massey 2000). This is formally analogous to the reduction and dismutation of cyclic enones by the same enzyme (Vaz et al. 1995), and the reductive fission of nitrate esters by an enzyme homologous to the old yellow enzyme from Saccharomyces cerevisiae (Snape et al. 1997). 

The transformation of A-nitrosodimethylamine by Pseudomonas mendocina KRl that has tolu-ene-4-monoxygenase activity was initiated by monooxygenation to the A-nitro compound, which produced A-nitromethylamine and formaldehyde, presumably by hydroxylation of the methyl group (Fournier et al. 2006). 

Alston TA, L Mela, HJ Bright (1977) 3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase. Proc Natl Acad USA 14 3767-3771. 

Anderson RC, MA Rasmussen, NS Jensen, MJ Allison (2000) Denitrobacterium detoxiflcans gen. nov., sp. nov., a ruminal bacterium that respires on nitrocompounds. Int J Syst Evol Microbiol 50 633-638. 

A stopped-flow examination of the alkaline permanganate oxidation of phenylnitromethane 

The kinetics and mechanisms of the MnO oxidations of nitrocyclohexane and nitrocyclopentane are entirely similar . The combined rate data for solutions at 0.5 M ionic strength are 

The use of chiral ligands on the jr-allylpalladium complexes leads to induction of chirality with however rather low optical yields [37]. 

Intramolecular attacks of jr-allyl Pd complexes or of aryl palladium intermediates have been applied to the synthesis of cyclic systems in fact, this type of reaction appears to be particularly interesting for the preparation of macrocyclic compounds. 

Similar reactions have been applied to humulene, macrolide [36] and steroid [57] synthesis and to the preparation of various heterocylic systems (Examples [22, 37, 38]). 

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The above are examples of the Claisen - Schmidt reaction. The formation of p-nitrostyrenes by reaction of nitroalkanes with aromatic aldehydes in the presence of aqueous alkali may be included under the Claisen- hmidt condensation ... 

The lower nitroalkanes (sometimes refered to as nitroparaffins) are easily reduced by a multitude of systems, but by far the easiest, and also the highest yielding, is the Iron/Hydrochloric acid system. The reaction is ... 

CAUTION - The lower nitroalkanes form shock and/or temperature sensitive EXPLOSIVE compounds with amines and hydroxides. BE CAREFUL, DAMNIT You have been warned. 

There exist a number of d -synthons, which are stabilized by the delocalization of the electron pair into orbitals of hetero atoms, although the nucleophilic centre remains at the carbon atom. From nitroalkanes anions may be formed in aqueous solutions (e.g. CHjNOj pK, = 10.2). Nitromethane and -ethane anions are particularly useful in synthesis. The cyanide anion is also a classical d -synthon (HCN pK = 9.1). 

Chemoselective C-alkylation of the highly acidic and enolic triacetic acid lactone 104 (pAl, = 4.94) and tetronic acid (pA, = 3.76) is possible by use of DBU[68]. No 0-alkylation takes place. The same compound 105 is obtained by the regioslective allylation of copper-protected methyl 3,5-dioxohexano-ate[69]. It is known that base-catalyzed alkylation of nitro compounds affords 0-alkylation products, and the smooth Pd-catalyzed C-allylation of nitroalkanes[38.39], nitroacetate[70], and phenylstilfonylnitromethane[71] is possible. Chemoselective C-allylation of nitroethane (106) or the nitroacetate 107 has been applied to the synthesis of the skeleton of the ergoline alkaloid 108[70]. 

Simple ketones and esters are inert. On the other hand, nitroalkanes react smoothly in r-butyl alcohol as a solvent with butadiene, and their acidic hydrogens are displaced with the octadienyl group. From nitromethane, three products, 64, 65, and 66, are formed, accompanied by 3-substituted 1,7-octadiene as a minor product. Hydrogenation of 65 affords a fatty amine 67 which has a primary amino function at the center of the long linear chain[46,61]. 

On the other hand, the carbonylation of the nitroalkane 100 at 190 °C using Pd on carbon and FeCl3 afforded the trialkylpyridine 101 [90],... 

C From indole-3-carboxaldehvdes by condensation with nitroalkanes ... 

Many of these reactions are reversible, and for the stronger nucleophiles they usually proceed the fastest. Typical examples are the addition of ammonia, amines, phosphines, and bisulfite. Alkaline conditions permit the addition of mercaptans, sulfides, ketones, nitroalkanes, and alcohols to acrylamide. Good examples of alcohol reactions are those involving polymeric alcohols such as poly(vinyl alcohol), cellulose, and starch. The alkaline conditions employed with these reactions result in partial hydrolysis of the amide, yielding mixed carbamojdethyl and carboxyethyl products. 

Nitromethane is the most reactive nitroalkane that favors strong reaction to the tris adduct (see Nitroalcohols). 

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 ... 

Higher nitroalkanes are prepared from lower primary nitroalkanes by a one-pot synthesis (69). Successive condensations with aldehydes and acylating agents are followed by reduction with sodium borohydride. Overall conversions in the 75—80% range are reported. 

CH—NHOH) to oxime (C=NOH) and ultimately to the nitroalkane (CH—NO2). Hydrogen peroxide generates amine oxides from tertiary cycloaUphatic... 

Titanium alkyls, known as tamed Grignard reagents, do not add to esters, nitriles, epoxides, or nitroalkanes at low temperatures. Rather, they add exclusively ia a 1,2 fashion to unsaturated aldehydes (208—210). 

A number of disinfectants apparentiy owe their activity to formaldehyde, although there is argument on whether some of them function by other mechanisms. In this category, the dmg with the longest history is hexamethylenetetramine (hexamine, urotropin) [100-97-0] which is a condensation product of formaldehyde and ammonia that breaks down by acid hydrolysis to produce formaldehyde. Hexamine was first used for urinary tract antisepsis. Other antimicrobials that are adducts of formaldehyde and amines have been made others are based on methylolate derivations of nitroalkanes. The apphcations of these compounds are widespread, including inactivation of bacterial endotoxin preservation of cosmetics, metal working fluids, and latex paint and use in spin finishes, textile impregnation, and secondary oil recovery (117). 

Reaction of various pyridazine derivatives with nitromethane or nitroethane in DMSO affords the corresponding 5-methyl and 5-ethyl derivatives. The reaction proceeds as a nucleophilic attack of the nitroalkane at the position 5. In this way, 3,6-dichloro-4-cyano-pyridazine, 4-carboxy- and 4-ethoxycarbonyl-pyridazin-3(2//)-ones and 4-carboxy- and 4-ethoxycarbonyl-pyridazin-6(lH)-ones can be alkylated at position 5 (77CPB1856). 

Trialkylisoxazoles have been prepared by the condensation of primary nitroalkanes under the influence of basic reagents (40JA2604). They can also be obtained from the reaction of a 1,3-diketone RCOCHRCOR with hydroxylamine hydrochloride <62HC(17)l, p. 54). 

A,V,V-trifliioroalkylamidines N-halogen compounds N-metal derivatives Nitroalkanes, c-nitro, and polynitroaryl compounds... 

Conversion of nitroalkanes to carbonyl compounds by acidification of nilronates. 

Can be purified by zone melting or by distn under vacuum at 0 , subjecting the middle fraction to several freeze-pump-thaw cycles. An impure sample containing higher nitroalkanes and traces of cyanoalkanes was purified (on the basis of its NMR spectrum) by crystn from diethyl ether at -60° (cooling in Dry-ice)(Parrett and Sun J Chem Educ 54 448 7977]. 

Nitroalkanes show a related relationship between kinetic acidity and thermodynamic acidity. Additional alkyl substituents on nitromethane retard the rate of proton removal although the equilibrium is more favorable for the more highly substituted derivatives. The alkyl groups have a strong stabilizing effect on the nitronate ion, but unfavorable steric effects are dominant at the transition state for proton removal. As a result, kinetic and thermodynamic acidity show opposite responses to alkyl substitution. 

This reaction can also be applied to tertiary nitroalkanes lacking any additional functional group. The reactions with nitro compounds lacking additional anion-stabilizing groups are carried out in DMSO solution ... 

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