Nitroalcohols compounds

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]. 

In 1992, Shibasaki et al. reported for the time an application of chiral heterobimetallic lanthanoid complexes (LnLB) as chiral catalysts in asymmetric catalysis, namely the catalytic asymmetric nitroaldol reaction (Henry reaction), which is one of the most classical C-C bond forming processes [11]. Additionally, this work represents the first enantioselective synthesis of (3-nitroalcohol compounds by the way of enantioselective addition of nitroalkanes to aldehydes in the presence of a chiral catalyst. The chiral BINOL based catalyst was prepared starting from anhydrous LaCl3 and an equimolar amount of the dialkali metal salt of BINOL in the presence of a small amount of water [9]. 

Nitropropane reacts with formaldehyde producing nitroalcohols CH3CH2CH2NO2 -h HCHO CH3CH2CH(N02)CH20H These difunctional compounds are versatile solvents, hut they are expensive. 

Alkenes can react with nitric acid, either neat or in a chlorinated solvent, to give a mixture of compounds, including v/c-dinitroalkane, jS-nitro-nitrate ester, v/c-dinitrate ester, /3-nitroalcohol, and nitroalkeneproducts. Cyclohexene reacts with 70 % nitric acid to yield a mixture of 1,2-dinitrocyclohexane and 2-nitrocyclohexanol nitrate. Frankel and Klager investigated the reactions of several alkenes with 70 % nitric acid, but only in the case of 2-nitro-2-butene (1) was a product identified, namely, 2,2,3-trinitrobutane (2). 

Interestingly, two of the other species in Table 3 are nitrolates, i.e. ethers of a-nitrooximes, an otherwise thermochemically unprecedented class of compounds. We already have briefly discussed one, 3-nitroisoxazoline, and the second is 1-nitroacetaldehyde 0-(l,l-dinitroethyl)oxime (ONo-ld-dinitroethyl acetonitronate), MeC (NOala—O—N=C(N02)Me. The latter acyclic species is a derivative of 1,1-dinitroethanol—we know of the enthalpy of formation of no other a-nitroalcohol or derivative. Nonetheless, we may ask if the two calorimetric data are internally consistent. Consider the condensed phase reaction 47, which involves formal cleavage of the O — bond in the nitroisoxazoline by the C—H bond of the dinitromethane. It is assumed that the isoxazoline has the same strain energy as the archetypal 5-atom ring species cyclopentane and cyclopentene, ca 30 kJ mol . ... 

Nitroalcohols 3a-j were isolated in good yields when a mixture of aromatic aldehydes 1 (10 mmol) and nitro compound 2 (10 mmol) adsorbed on Si02 (finer than 200 mesh, 5 g) and taken in a open Pyrex test tube was subjected to micro-wave irradiation in a domestic microwave oven (BPL, BMO 700T) at an out-put of about 600 W. After cooling the reaction mass to room temperature, the products were isolated by extracting with dichloromethane and evaporation of the sol-... 

Since many nitrogen-containing organic compounds are explosive, some mention is appropriate here of possible hazards in working with nitromethane. Occasionally, some evidence of decomposition, in the form of mild evolution of heat and gases, has been observed by the author in concentrated, acidified aldose-nitromethane reaction residues from which the bulk of the nitroalcohols had been separated. Such residues usually have been either discarded at once or stored at —20° when further crystallization was anticipated. Generally, it may be stated that the aldose-nitromethane condensation reaction does not involve serious explosion hazards. 

A very characteristic feature of primary and secondary nitro compounds is their ability to add on aldehydes in a weak basic medium to form nitroalcohols (X, XI). Formaldehyde is particularly readily added ... 

In order to increase the exchange rate, ten equivalents of triethylamine were added, and the dynamic system was generated at 40 °C. Figure 5 shows 1H-NMR spectra of the dynamic nitroaldol system at different reaction times. In the absence of any catalyst, none of the nitroalcohol adducts was observed, but addition of triethylamine resulted in efficient equilibrium formation (Fig. 5a). The aldehyde protons of compounds 18A-E were easily followed (10.0-10.5 ppm), as well as the a-protons of 2-nitropropane 19 and adducts 20A-E (4.5-6.5 ppm). The selected dynamic nitroaldol reaction proved to be stable without producing any side reactions within several days. 

The Henry reaction or the nitroaldol is a classical reaction where the a-anion of an alkyinitro compound reacts with an aldehyde or ketone to form a p-nitroalcohol adduct. Over the decades, the Henry reaction has been used to synthesize natural products and pharmaceutical intermediates. In addition, asyimnetric catalysis has allowed this venerable reaction to contribute to a plethora of stereoselective aldol condensations. Reviews (a) Ballini, R. Bosica, G. Fiorini, D. Palmieri, A. Front. Nat. Prod. Chem. 2005, 1, 37-41. (b) Ono, N. In The Nitro Group in Organic Synthesis Wiley-VCH Weinheim, 2001 Chapter 3 The Nitro-Aldol (Henry) Reaction, pp. 30-69. (c) Luzzio, F. A. Tetrahedron 2001, 57, 915-945. 

The Henry (or nitro-aldol) reaction is one of the powerful carbon-carbon bond formation reactions frequently used in organic synthesis, providing access (via coupling between a carbonyl compound and an alkylnitro compound) to P-nitroalcohols, useful synthons in organic synthesis (Scheme 16.26) [160]. 

An electrochemical-induced Henry reaction has been achieved by Elinson et al. via electrolysis (undivided cell) of solutions of carbonyl compounds and nitromethane in methanol or in methanol-DMF mixture containing alkali metal iodide as supporting electrolyte. p-Nitroalcohols have been isolated in 60-75% yields. The authors suggest that the Henry reaction could be induced by the deprotonation of methanol at the cathode and by the oxidation of the iodide anion at the anode (Scheme 16.27) [165]. 

Aliphatic dinitro compounds, nitronitric acid esters, and nitroalcohols from olefins... 

Fig. 4.1 A typical infrared spectrum of liquid nitro compounds, a Nitromethane, b Nitrobezene, c O-Nitrotoluene, d Nitroalcohol...

Fridman AL, Kremleva OB, Zalesov VS (1977) Syn-thesis and study of the physiological activity of aliphatic nitro compounds. Xll. Relation among strucmre, toxicity, and bacterio static activity in a series of beta-nitroalcohols. Khim-FarmZh ll(l) 73-75... 

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