2-nitroalcohol

The preparation of nitroaUtane is very difficult, and it is more difficult to prepare nitro alcohols. In most of the early nitroalcohol preparation methods, oxidation nitration method was used to obtain the target products, DNPOH [37, 38] was also produced with oxidation nitration method and chlorination nitration method [39]. Disadvantages of these nitro alcohol preparation methods is The oxidized nitration 

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

Nitroalcohols undergo addition to isopropyl 2,2-difluorovinyl ketone and isopropyl 3,3-difluoroacrylate in the presence of amines [6] (equation 5)... 

Method A ct,ct-Donbly deprotonated nitroalkanes react with aldehydes to give intermediate nitronate alkoxides, which afford iyti-nitroalcohols as major products d8 7-47 3 by kmedc protonadon at -100 C in THF-HMPA. The carcinogenic hexamethylphosphorons triamide fHMPAi can be replaced by the ntea derivadve (T)MPU. ... 

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

Intermolecular reaction of the mannose-derived 2,3-0-isopropylideiie-a-D-/y.vc>-pentodialdo-l,4-furanoside 13 affords a diastereomeric mixture of nitroalcohols 14. Upon fluoride-catalyzed desilylation, a stereoisomerically pure nitrocyclitol 15 was obtained from a successive intramolecular nitroaldol reaction as a consequence of the reversibility of the nitroaldol reaction which, in this case, allows the equilibration of isomers through open-chain intermediates33. 

In addition, highly enantioselective nitroaldol reactions were performed by Bandini et al. by using a new class of C2-symmetric oligothiophene ligands, in 2007. Thus, associated to copper, these C2-symmetric bis(amino) ligands allowed the synthesis of a wide range of enantiomerically enriched nitroalcohols... 

The Henry (nitroaldol) reaction was reported under very mild reaction conditions, in aqueous media using a stoichiometric amount of a nitroalkane and an aldehyde, in NaOH 0.025 M and in the presence of cetyltrimethylammonium chloride (CTAC1) as cationic surfactant (Eq. 8.94) 240 Good to excellent yields of (i-nitroalkanol are obtained. Under these conditions several functionalities are preserved, and side-reactions such as retro-aldol reaction or dehydration of 2-nitroalcohols are avoided. 

A very attractive method for the preparation of nitroalkenes, which is based on the reaction with NO, has been reported. Treatment of alkenes at ambient pressure of nitrogen monoxide (NO) at room temperature gives the corresponding nitroalkenes in fairly good yields along with P-nitroalcohols in a ratio of about 8 to 2. The nitroalcohol by-products are converted into the desired nitroalkenes by dehydration with acidic alumina in high total yield. This simple and convenient nitration procedure is applied successfully to the preparation of nitroalkenes derived from various terminal alkenes or styrenes (Eq. 2.27).53 This process is modified by the use of HY-zeolites instead of alumina. The lack of corrosiveness and the ability to regenerate and reuse the catalyst make this an attractive system (Eq. 2.28).54... 

The enantioselective nitroaldol reaction of phe-nylalaninals 45 with nitromethane was also promoted with the N-anthracenylmethyl ammonium fluorides in the presence of potassium fluoride.1411 Interestingly, as shown in Scheme 16, the major product was the (2R,3S)-isomer 46a when N,N-dibenzyl-(S)-phenylalaninal and 12 (R=benzyl, X=F) were used while the (2S,3S)-isomer 46b was major when N-tert-butoxycarbonyl derivative 45b and 12 (R=allyl, X=Br) together with potassium fluoride were used. The nitroalcohols 46a and 46b were respectively converted to amprenavir 47a, a HIV protease inhibitor, and its diastereomer 47b. The... 

Phosphorylated derivatives of /3-nitroalcohols, upon exposure to Bu3SnH and AIBN, afford /3-(phosphatoxy)alkyl radicals. These radicals undergo heterolytic cleavage of the phosphate group to afford an alkene radical cation which is trapped intramolecularly in a tandem polar/radical crossover sequence. Derivative 37 (Scheme 13), through a 6-exol 5-exo overall cyclization, afforded the indolizidine derivative 38 as an equimolecular mixture of two diastereoisomers <2003JA7942, 2002OL2573>. 

The procedure described in Sect. 14.9.1 for addition of nitroalkane anions to activated alkenes can also be used for addition to aldehydes. The nitroalcohol formed can be dehydrated in almost quantitative yields in dilute H3PO4 in a subsequent step [130, 131]. Starting with... 

Toxie and biologically resistant materials will require special consideration for their treatment. You will need to adjust the nutrient stream to aeeommodate the bacteria in the system and aid in the hydrolysis of the eompounds or even wash or chelate the toxic metals out of the way. In one waste stream where nitroalcohols were being treated, the system required 42 days of detention in order to provide sufficient dilution and residence time to allow speeialized enzymes to develop in the bacterial population. 

The DCL was generated from equimolar amounts of five different aromatic aldehydes (24, 26, 27, 36, and 37) and 2-nitropropane (38) to provide 10 3-nitroalcohol substrates including all enantiomers (DCL-E, Scheme 6.9). 

Figure 6.13 displays H-NMR analysis of the resulting (3-nitroalcohol DCL. Aher mixing benzaldehydes (24, 26, 27, 36, and 37) with 2-nitropropane (38), equilibration was initiated by the addition of triethyl-amine. To allow faster equilibration, the exchange took place at 40°C, and all adducts were clearly present at equilibrium that was established afier 18 hours. Equilibration also worked well at ambient temperature, albeit showing slower rates. Temperatures above 40°C, however, had a negative influence on the enantioselectivity of the subsequent enzymatic reaction and also caused slow decomposition of the (3-nitroalcohol substrates. 

Lipase-catalyzed transesterification of (3-nitroalcohol substrates had not previously been reported and required careful optimization of the reaction conditions. A series of enzymes were screened, followed by acyl donors. From these results, the lipase Pseudomonas cepacia (PS-C I) (for more... 

The nitroaldol-lipase DCR process could not only amplify specific (3-nitroalcohol derivatives, but also lead to their asymmetric discrimination. HPLC analysis proved that the enantioselectivity of the process is very high, resulting in products of very high optical purity. The R-enantiomer of the ester 45 was resolved to 99% ee, and the R-enantiomer of the ester 46 to 98% ee. 

Internal DCR of Nitroaldol Libraries (Scheme 6.10) [5,6] iDCR was demonstrated by using a conceptual nitroaldol library including five benzaldehyde derivatives (24,36, and 47-49) and one nitroalkane (50, DCL-F, Scheme 6.11). The benzaldehydes, all with a unique substitution pattern, were selected in order to make analysis clear and simple. However, one of the henzaldehydes contained a cyano functionality in the 2-position (49), deliberately making it a candidate for subsequent tandem cyclization following nitroalcohol formation. 5-exo-dig type cyclizations of hydrox-ynitriles to the corresponding iminolactones are expected [40,41], albeit unexplored [42 5], intramolecular transformations, which in this case could lead to possible kinetic resolution of the library. 

To initiate the equilibrium, triethylamine was added and the reaction followed frequently by H-NMR. Under these conditions, equilibrium was reached within 3 hours (Fig. 6.15). Following this, the full hbrary (DCL-F) including aldehyde (49) was constructed. This library initially behaved similarly to DCL-G, with several nitroaldoladducts forming competitively. A total of 20 individual (3-nitroalcohol adducts is possible including enantiomers and diastereoisomers. However, within 1 hour, a clear amplification of a single diastereomeric pair, supposedly iminolactone (56), became clearly visible. The amphfication effect then gradually continued until all... 

Figure 6.17 Reaction composition followed over time ( ) aldehyde (49), (O) nitroalcohol intermediate (55), and (A) product (57) (modified from Reference 6). Lines represent fitted data from kinetic model [49],...

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). 

The reaction of fuming nitric acid with 2-methyl-2-butene (3) is reported to yield 2-methyl-3-nitro-2-butene (4). The reaction of alkenes with fuming nitric acid, either neat or in chlorinated solvents, is an important route to unsaturated nitrosteroids, which assumedly arise from the dehydration of /3-nitroalcohols or the elimination of nitric acid from /3-nitro-nitrate esters. Temperature control in these reactions is important if an excess of oxidation by-products is to be avoided. 

The observant may ask, Why does the alkoxide anion of the nitroalcohol not add to the Michael acceptor The addition of alkoxide anions to Michael acceptors is well known, but... 

Synthetic routes to a-nitroalkenes have been discussed in previous sections. General routes include (1) treating /3-nitroacetates with alkali metal acetates, carbonates or bicarbonates, (2) elimination of water from /3-nitroalcohols via heating with phthalic anhydride or in the presence of a base," ° and (3) degradation of the Mannich products derived from a primary nitroalkane, formaldehyde, and a secondary amine. ... 

Polynitroaliphatic alcohols are invaluable intermediates for the synthesis of energetic materials (see Section 1.11). The most important route to /i-nitroalcohols is via the Henry reaction where a mixture of the aldehyde and nitroalkane is treated with a catalytic amount of base, or the nitronate salt of the nitroalkane is used directly, in which case, on reaction completion, the reaction mixture is acidified with a weak acid. Reactions are reversible and in the presence of base the salt of the nitroalkane and the free aldehyde are reformed. This reverse reaction is known as demethylolation if formaldehyde is formed. 

The nitroalcohol precursor was resolved by the lipase-catalyzed acylation of the hydroxy group. The nitrobutyraldehyde was obtained by acid-mediated hydrolysis of the nitrodiethylacetal and used directly in the aldolization reaction after pH adjustment to 7.5. 

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 . ... 

C), various (hetero)aromatic aldehydes were transformed into nitroalcohols 1-6 in consistently high yields (90-99%) and ee values (86-92%) as shown in Scheme 6.146. The protocol failed for aliphatic aldehydes such as cyclohexanecar-boxaldehyde and isobutyraldehyde that displayed incomplete conversion to the respective nitroalcohols even after 1 week reaction time and gave low ee values (<20%) of the adducts. Catalyst 132, the pseudoenantiomer of 131, gave access to nitroalcohols with the opposite configuration and comparable enantiomeric excess, as exemplified for three aldehydes (e.g., (R)-adduct 3 87% yield 93% ee). 

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