Nitroalkanes structure

The Henry reactions of A, ALdibenzyl-L-phenylalaninal with nitroalkanes using 1.2 equiv of tetrabutylammonium fluoride (TBAF) as the catalyst proceed in ahighly stereoselective manner, as shown in Eqs. 3.82 and 3.83. This reaction provides rapid and stereoselective access to important molecules containing 1,3-diamino-2-hydroxypropyl segments, which are cenhal structural subunit of the HIV protease inhibitor amprenavir (in Scheme 3.21). 

The reduction of nitroalkenes with ZnBH4 in 1,2-dimethoxyethane (DME) gives the corresponding oximes or nitroalkanes depending on the structure of nitroalkenes. a-Substituted nitroalkenes are reduced to the oximes, whereas those having no a-substituents afford the... 

The conjugate addition of nitroalkanes to a,P-unsaturated aldehydes (Sect. 2.2.2) has been investigated by Uggerud, who compared the uncatalysed, proton catalysed and iminium ion catalysed additions [232]. The results suggested that protonated acrolein was more activated towards addition than the iminium ion catalysed process and also indicated that an intermediate oxazolidin structure 183, unobserved experimentally, may be involved in the reaction pathway (Fig. 17) with the transition state resembling that of a [3+2] cycloaddition process. 

Isoxazoline derivatives of Cgo such as 250 (Scheme 4.40) are accessible by 1,3-dipolar cycloadditions of nitrile oxides to [6,6] double bonds of the fullerene [2, 278, 291-305]. The nitrile oxides 249 with R = methyl, ethyl, ethoxycarbonyl and anthryl are generated in situ from the corresponding nitroalkane, phenyl isocyanate and triethylamine. The isoxazoline derivative of Cgo 250 (with R = anthryl) crystallizes in black prisms out of a solvent mixture of CS2 and acetone (3 2) [292]. X-ray crystal structure analysis shows that addition of the nitrile oxide occurs on a [6,6] double bond of the fullerene framework. 

For synthesis of more complex target molecules by these strategies, nitroalkanes with additional O-functions are often required. Specifically, the above CC-forming additions lead to a variety of 1,3,4-, 1,3,5- and 1,3,6-functionalized structures, as shown with 3 (or nitropropyl ethers, from 2). 

Nitro-compounds fRNOj) are isomeric with nitrites, but their electronic structure, excited states and photochemistry are very different. There is no very low-lying (n.jt ) state, and nitroalkanes show n — 3i absorption with a maximum around 275 nm ( —201 mol - cm In cyclohexane solution, nitromethane (CH1NOi) is photoreduced to nitrosomethane(CH,NO, but nitroethane under the same conditions gives rise to a nitroso-dimer derived from the solvent CS.47). The latter process is probably initiated by cleavage of the carbon-nitrogen bond in the nitroalkane. In basic solution (when the nitroalkane is converted to a nitronate anion) irradiation can lead to efficient formation of a hydroxamic acid (S.48), and this reaction most likely proceeds through formation of an intermediate three-mem bered cyclic species. 

The most important reactions of nitroalkan.es are those involving the a hydrogens of the primary and secondary compounds. For example, nitro-methane is sufficiently acidic to dissolve in aqueous hydroxide solutions. The anion so produced has an electronic structure analogous to the nitrate anion ... 

Kinetics of the gas-phase elimination of 2-hydroxynitroalkanes have been investigated at the MP2/6-31G level of theory.31 The thermal elimination of 2-hydroxynitroalkanes occurs in a retro-aldol type of mechanism with a six-membered transition state structure characterized by the transference of the hydroxyl hydrogen to the nitro group to give acetaldehyde and the corresponding nitroalkane for the secondary substrates and acetone and nitromethane for the tertiary substrate. 

Vanaken, E., Wynberg, H. and Vanbolhuis, F. Nitroalkanes in C-C bond forming reactions - A crystal-structure of a complex of a guanidine catalyst and a nitroalkane substrate, J. Chem. Soc., Chem. Commun., 1992, 629-630. 

The enolate A or the nitronate A, respectively, initially adds to the C=0 double bond of the aldehyde or the ketone. The primary product in both cases is an alkox-ide, D, which again contains the structural motif of a fairly strong C,H-acid, namely, of an active-methylene compound or of a nitroalkane, respectively. Hence, intermediate D is protonated at the alkoxide oxygen and the C-/3 atom is deprotonated to about the same extent as in the case of the starting materials. An OH-substituted enolate C is formed (Figures 10.45 and 10.46), which then undergoes an Elcb elimination, lead-... 

Reaction of nitroalkenes with Grignard reagents gives 7-salts, which, depending on the hydrolysis conditions and substrate structure, can be transformed into nitroalkanes, hydroxymoyl halides, or carboxylic acids.241 Reaction of... 

The clearest example of the danger in using a as a measure of transition state structure is illustrated in the work of Bordwell et al. (1969, 1970, 1975). In the rate-equilibrium relationship for the deprotonation of a series of nitroalkanes the unprecedented Br nsted slopes of 1 61 for l-aryl-2-nitropropanes and 1-37 for 1-arylnitro-ethanes were obtained. The simple exposition of the mechanistic significance of a disallows values greater than 1. This, coupled with the fact that the transition state for the proton transfer is not product-like (as established by alternative criteria) indicates at best that, in at least some cases, a does not reflect the selectivity of a particular reaction. Several attempts to rationalize these anomalous results have been made. 

An alternative view has been presented based on Marcus theory (Marcus, 1968, 1969). If AG for a reaction is expressed in terms of AG° and the intrinsic barrier, A/4, [eqn (17)], then it can be shown that the Br nsted slope will lie between 0 and 1 for a family of reactions which shares the same intrinsic barrier. In such cases the magnitude of a will reflect the position of the transition state along the reaction co-ordinate. Since AG for nitroalkanes is relatively high (i.e. A/4 is large), changes in R [eqn (23)] are expected to alter the magnitude of A/4. In such an event a ceases to be a measure of transition state structure. 

The nitroaldol (Henry) reaction, first described in 1859, is a carbon-carbon bondforming reaction between an aldehyde or ketone and a nitroalkane, leading to a nitroalcohol adduct [29]. The nitroalcohol compounds, synthetically versatile functionalized structural motifs, can be transformed to many important functional groups, such as 1,2-amino alcohols and a-hydroxy carboxylic acids, common in chemical and biological structures [18, 20, 30, 31]. Because of their important structural transformations, new synthetic routes using transition metal catalysis and enzyme-catalyzed reactions have been developed to prepare enantiomerically pure nitroaldol adducts [32-34]. 

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