Nitronate ions

Nitroparaffins and HBF react with alkynes through conjugate addition of a proton and the nitronate ion at the triple bond as illustrated by nitromethane and 5-decyne (53). 

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. 

Crozet and co-workers have used Spj l reactions for synthesis of new heterocycles, which are expected to be biologically active fsee iilso Section 7 3, which discusses synthesis of alkenesi For example, 2-chloromethyl-5-nitroimidazole reacts v/ith theanionof 2-nitropropane to give 2-isopropylidene-5-nitroimida2ole It is formed via C-alkyladon of the nitronate ion followed by eliminadon of HNCk fEq 5 33 Other derivadves of nitroimidazoles are idso good substrates for Spj ... 

The reactions of the lithium enolates of substituted 2-cyclohexenones and 2-cyclopentenones with ( )-l-nitropropene give a mixture of syn- and ami-products3. The lithium enolate of 3,5,5-trimethyl-2-cyclohexenone gives a mixture of the syn- and //-3.5,5-trimethyl-6-(l-methyl-2-nitroethyl)-2-cyclohexcnoncs in modest diastereoselection when the reaction mixture is quenched with acetic acid after. 30 minutes at —78 =C. When the reaction mixture is heated to reflux, tricyclic products are obtained resulting from intramolecular Michael addition of the intermediate nitronate ion to the enone moiety. 

The condensation of nitro compounds and imines, the so-called aza-Henry or nitro-Mannich reaction, has recently emerged as a powerful tool for the enantioselective synthesis of 1,2-diamines through the intermediate /3-amino nitro compounds. The method is based on the addition of a nitronate ion (a-nitro carbanion), generated from nitroalkanes, to an imine. The addition of a nitronate ion to an imine is thermodynamically disfavored, so that the presence of a protic species or a Lewis acid is required, to activate the imine and/or to quench the adduct. The acidic medium is compatible with the existence of the nitronate anion, as acetic acid and nitromethane have comparable acidities. Moreover, the products are often unstable, either for the reversibility of the addition or for the possible /3-elimination of the nitro group, and the crude products are generally reduced, avoiding purification to give the desired 1,2-diamines. Hence, the nitronate ion is an equivalent of an a-amino carbanion. 

Like the nitronate ion, the cyanide ion is synthetically equivalent to the aminomethyl carbanion (CH2NH2) , because of the possible reduction of - CN to the - CH2NH2 group. Consequently, the addition of cyanide ion to imines to give a-aminonitriles (Strecker-type reaction) is a viable route to 1,2-diamines. As a matter of fact, a number of diastereoselective and catalytic... 

As previously described, in basic conditions the proUne-derived a-sulfonyl amide 141 generates the imine function, which afterwards undergoes addition by a nucleophile, e.g., a nitronate ion see the diastereoselective synthesis of the diamino nitroalkane derivative 172, which is the precursor of the piperazine-2-carboxyUc acid 173, through a Nef reaction [45]. Similarly, the addition of the Uthium enolate of ethyl acetateto the a-sulfonyl amide 174 gave the diamino ester derivative 175, wich was then converted to (-)-l-aminopyrrolizidine 176 (Scheme 27). 

The secondary /3-deuterium KIEs observed for the reaction of the same substrate with hydroxide ion and with tris(hydroxymethyl)methylamine in aqueous solution at 25°C were small, i.e. kH/kD = 1.09 0.01 and 1.10 0.01, respectively. While Kresge argued that the EIE was primarily due to hyperconjugation, the secondary /3-deuterium KIEs were attributed partly to hyperconjugation and partly to a polar (inductive) effect. The rate constants for the evaluation of both the EIE and the KIEs were determined in separate kinetic runs by following the increase in the absorbance due to the nitronate ion by UV spectroscopy. 

Decarboxylation of 1,3-dimethylorotic acid in the presence of benzyl bromide yields 6-benzyl-1,3-dimethyluracil and presumably involves a C(6) centered nucleophilic intermediate which could nonetheless have either a carbene or ylide structure. Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry has been used to explore the gas-phase reactions of methyl nitrate with anions from active methylene compounds anions of aliphatic ketones and nitriles react by the 5n2 mechanism and Fco reactions yielding N02 ions are also observed nitronate ions are formed on reaction with the carbanions derived from toluenes and methylpyridines. 

Substrates with doubly bonded nitrogen-atom functionalities, e.g. the C=N-R (imino, oxime) group, are usually cleaved by dioxirane to give the corresponding carbonyl product" . A particular case represents the DMD oxidation of the nitronate ions, generated from nitroalkanes" or nitroarenes. For example, the nitronate anion 16 (equation 13) affords initially the cyclohexadienone on oxidation with DMD, which subsequently tau-tomerizes to the phenol as the final product. An exception is the DMD oxidation of an... 

Nitrobenzene chloride, sulfonylperoxy radical reactions, 1035, 1036 2-Nitrobenzenesulfinylperoxy intermediate, superoxide reactions, 1034 Nitrogen-containing compound oxidation bis(trimethylsilyl) peroxide reactions, 802-3, 804 dioxiranes, 1151-5 primary aromatic amines, 1151 A-oxidation, 531-8, 539 Nitrohpids, hpid hydroperoxides, 952-4 Nitronate ions, dioxirane oxidation, 1152-3 Nitrosation, malondialdehyde, 667 Nitroso compounds, spin trapping, 664 Nitrotyrosine, peroxynitiite determination, 740-1... 

As the Connolly studies suggested (Sect. 3.5), protonated concave pyridines should be able to discriminate between small and large molecules. In a model reaction, a protonation reaction has therefore been examined. The protonation of nitronate ions 44 has been chosen [35] (Scheme 8). In these ions an intramolecular competition of carbon versus oxygen protonation leads to nitro (45) or flci-nitro (46) compounds. The latter ones may then be hydrolyzed by way of the Nef-reaction [36] to form carbonyl compounds 47. 

The Soft Nef-Reaction was carried out with different nitronate ions 44 and different buffers as shown in Table 2 [38]. As expected the use of p-toluenesulfonic acid (48) alone resulted in the formation of the Nef-products 47 whereas pyridine (50) and 2,6-dimethylpyridine (51) buffers gave the nitro compounds 45. 

Table 2. Competition between C-protonation (formation of nitro compounds 45) and O-proton-ation (formation of the Nef-product 47) in the protonation of nitronate ions 44 (s. Scheme 8). The percentage of C-protonated product 45 for different buffers (pyridine/p-toluenesulfonic acid) and unbuffered p-toluenesulfonic acid (48) is listed...

Tables. The protonation of the nitronate ions 44c and 44d by protonated 2-aryl-l,10-phenanthrolines 52 leads to threojerythro or cis/trans mixtures of the products 45c or 4M, respectively (s. Table 2)...

The high selectivities found in the protonation experiments of the nitronate ions 44 suggested that also allyl anions 54 can be regioselectively protonated by a general acid protonation. Therefore, some lithium allyl compounds (Structures 6) were generated by deprotonation of alkenes with n-butyl lithium. 

Selectivity increases by the use of buffers of concave bases were found for the protonation of nitronate ions 44 (s. Scheme 8). Three interesting results have been found ... 

Substrate selectivity (differentiation between 1° and 2° nitronate ions)... 

In the protonation of nitronate ion 44d, a solvent dependence of the stereoselectivity was found. Alcohols gave the highest selectivities [20, 40]... 

In cases where there is strong solvation of the carbanion, as for example hydrogen bonding solvation of enolate or nitronate ions in hydroxylic solvents, the intrinsic barrier is increased further because the transition state cannot benefit significantly from this solvation. This is the reason why AG for the deprotonation of nitroalkanes in water is particularly high, i.e., much higher than in dipolar aprotic solvents, see, e.g., entry 11 versus 15 and entry 13 versus 16 in Table 1. These solvation effects will be discussed in more detail below. 

This hyperconjugation contributes to the stability of the respective nitronate ions as reflected in the reduction of the pKA values for H0CH2CH2N02 (pifa = 9.40) and PhCH2CH2N02 (p/y, 8.55) relative to CH3N02... 

A. S. Ni, J. X. Kinetics of ionization of nitro-methane and phenylnitromethane by amines and carboxylate ions in DMSO-water mixtures. Evidence of ammonium ion—nitronate ion hydrogen bonded complex formation in DMSO-rich solvent mixtures./. Org. Chem. 1988, 53, 3342-3351. 

Fig. 28. Conformation analyses for proton abstraction from 2-R-nitrocyclohexane and the protonation of the nitronate ions. See also equation (216).

The nitro group does not necessarily have to be in the o- or -position of the benzene ring, nor is the presence of a nitro group a prerequisite for nucleophilic photosubstitution via the S l mechanism to occur. The meta-nitro analogue 35 with a tert-butyl group at Ca displays S l behaviour (with a series of nucleophiles)197 and so do the bridgehead halide 9-bromotriptycene (with phosphide and arsenide ions)32, compound 36 (with nitronate and azide ions)1, compound 37, X = Cl (with nitronate ions)199 and compound 38 (with azide ion)200. For compound 37, X = Br, SN2 substitution is competitive. 

The possible reversibility of the C-alkylation of nitronate anions under S l conditions was studied by examining the degree of interconversion of the C-alkylation product 3 and 4 in crossed experiments with the nitronate ions 5 and 669. 

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