Palladium-Catalyzed α-Arylation of Aryl Nitromethanes.

Catalytic conditions for the α-arylation of aryl nitromethanes have been discovered using parallel microscale experimentation, despite two prior reports of the lack of reactivity of these aryl nitromethane precursors. The method efficiently provides a variety of substituted, isolable diaryl nitromethanes. In addition, it is possible to sequentially append two different aryl groups to nitromethane. Mild oxidation conditions were identified to afford the corresponding benzophenones via the Nef reaction, and reduction conditions were optimized to afford several diaryl methylamines.

Minimizing the amount of nitromethane in palladium-catalyzed cross-coupling with aryl halides.

A method for the formation of arylnitromethanes is described that employs readily available aryl halides or triflates and small amounts of nitromethane in a dioxane solvent, thereby reducing the hazards associated with this reagent. Specifically, 2-10 equiv (1-5% v/v) of nitromethane can be employed in comparison to prior work that used nitromethane as solvent (185 equiv). The present transformation provides high yields at relatively low temperatures and tolerates an array of functionality, including heterocycles and substantial steric encumbrance.

Synthesis and stereochemical analysis of ß-nitromethane substituted γ-amino acids and peptides.

The high diastereoselectivity in the Michael addition of nitromethane to α,ß-unsaturated γ-amino esters, crystal conformations of ß-nitromethane substituted γ-amino acids and peptides are studied. Results suggest that the N-Boc protected amide NH, conformations of α,ß-unsaturated γ-amino esters and alkyl side chains play a crucial role in dictating the high diastereoselectivity of nitromethane addition to E-vinylogous amino esters. Investigation of the crystal conformations of both α,ß-unsaturated γ-amino esters and the Michael addition products suggests that an H-C(γ)-C(ß)=C(α) eclipsed conformer of the unsaturated amino ester leads to the major (anti) product compared to that of an N-C(γ)-C(ß)=C(α) eclipsed conformer. The major diastereomers were separated and subjected to the peptide synthesis. The single crystal analysis of the dipeptide containing ß-nitromethane substituted γ-amino acids reveals a helical type of folded conformation with an isolated H-bond involving a nine-atom pseudocycle.

Highly enantioselective hydrogenation of ß,ß-disubstituted nitroalkenes.

Building the building blocks: A highly enantioselective hydrogenation of ß-aryl-ß-alkyl disubstituted nitroalkenes 1 has been developed. This method results in enantiomerically pure nitroalkanes 2, which are versatile precursors for chemical synthesis.

Pyrrolidinyl-sulfamide derivatives as a new class of bifunctional organocatalysts for direct asymmetric Michael addition of cyclohexanone to nitroalkenes.

A series of chiral pyrrolidinyl-sulfamide derivatives have been identified as efficient bifunctional organocatalysts for the direct Michael addition of cyclohexanone to a wide range of nitroalkenes. The desired Michael adducts were obtained in high chemical yields and excellent stereoselectivities (up to 99/1 dr and 95% ee).

Impact of UV disinfection combined with chlorination/chloramination on the formation of halonitromethanes and haloacetonitriles in drinking water.

The application of UV disinfection in water treatment is increasing due to both its effectiveness against protozoan pathogens, and the perception that its lack of chemical inputs would minimize disinfection byproduct formation. However, previous research has indicated that treatment of nitrate-containing drinking waters with polychromatic medium pressure (MP), but not monochromatic (254 nm) low pressure (LP), UV lamps followed by chlorination could promote chloropicrin formation. To better understand this phenomenon, conditions promoting the formation of the full suite of chlorinated halonitromethanes and haloacetonitriles were studied. MP UV/postchlorination of authentic filter effluent waters increased chloropicrin formation up to an order of magnitude above the 0.19 µg/L median level in the U.S. EPA's Information Collection Rule database, even at disinfection-level fluences (<300 mJ/cm(2)) and nitrate/nitrite concentrations (1.0 mg/L-N) relevant to drinking waters. Formation was up to 2.5 times higher for postchlorination than for postchloramination. Experiments indicated that the nitrating agent, NO(2)(•), generated during nitrate photolysis, was primarily responsible for halonitromethane promotion. LP UV treatment up to 1500 mJ/cm(2) did not enhance halonitromethane formation. Although MP UV/postchloramination enhanced dichloroacetonitrile formation with Sigma-Aldrich humic acid, formation was not significant in field waters. Prechlorination/MP UV nearly doubled chloropicrin formation compared to MP UV/postchlorination, but effects on haloacetonitrile formation were not significant.

Preparation of D-galactofuranosyl nitromethanes: a revision and a new approach.

Sodium methoxide-promoted methanolysis of 7-deoxy-7-nitro-L-glycero-L-galacto-heptitol peracetate rapidly and nearly quantitatively accumulates 7-deoxy-6-O-methyl-7-nitro-L-glycero-L-galacto-heptitol. The prolonged treatment then provides 76% of D-galactofuranosyl nitromethanes and finally results in the equilibrium of 77% of ß-D-galactopyranosyl nitromethane and 7-9% of three other tautomeric D-galactosyl nitromethanes. Thermal treatment of 7-deoxy-7-nitro-L-glycero-L-galacto-heptitol in boiling water peaks at a 58% content of D-galactofuranosyl nitromethanes and ends in a similar equilibrium mixture of four D-galactosyl tautomers. The relevant kinetic parameters of the latter transformation are determined by a curve fitting using the nonlinear least-squares Marquardt-Levenberg algorithm.

Formation of disinfection by-products in indoor swimming pool water: the contribution from filling water natural organic matter and swimmer body fluids.

The contribution and role of different precursors in the formation of three class of disinfection by-products (DBPs) [trihalomethanes (THMs), haloacetic acids (HAAs), and halonitromethanes (HNMs)] in swimming pool waters were examined using filling waters obtained from five drinking water treatment plant (WTP) effluents and three body fluid analogs (BFAs). BFAs exerted higher chlorine demands as compared to natural organic matter (NOM) in filling waters. BFAs exhibited higher HAA formation potentials than THM formation potentials, while the opposite was observed for the filling water NOM. There was no appreciable difference in the HNM formation potentials of BFAs and filling water NOM. Different components in the BFAs tested exhibited different degree and type of DBP formation. Citric acid had significantly higher THM and HAA yields than other BFA components. The effect of temperature was greater on THM formation, whereas the effect of contact time had more impact on HAA formation. Experiments with filling waters collected from WTP effluents at three different times showed more variability in HAA than THM formation at the WTPs studied.

Synthesis of (11)C-labeled 2-aminoethanol via a nitroaldol reaction using nitro[(11)C]methane.

The nitroaldol reaction of nitro[(11)C]methane and formaldehyde using EtOH and EtONa efficiently provided 2-nitro[(11)C]ethanol in 3min. The nitro group reduction in the presence of NiCl(2) and NaBH(4) in MeOH followed by purification using semi-preparative HPLC using 10% EtOH aqueous solution as an eluent proved to be a practical and accessible method for the synthesis of 2-amino[2-(11)C]ethanol.

Vicinal nitrohydroxyeicosatrienoic acids: vasodilator lipids formed by reaction of nitrogen dioxide with arachidonic acid.

Nitric oxide (NO)-derived species could potentially react with arachidonic acid to generate novel vasoactive metabolites. We studied the reaction of arachidonic acid with nitrogen dioxide (NO2), a free radical that originates from NO oxidation. The reaction mixture contained lipid products that relaxed endothelium-removed bovine coronary arteries. Relaxation to the lipid mixture was inhibited approximately 20% by indomethacin and approximately 70% by a soluble guanylate cyclase (sGC) inhibitor (ODQ). Thus, novel lipid products, which activate sGC presumably through a mechanism involving NO, appeared to have contributed to the observed vasorelaxation. Lipids that eluted at 9 to 12 min during high-performance liquid chromatography fractionation accounted for about one-half of the vasodilator activity in the reaction mixture, which was inhibited by ODQ. Lipid products in fractions 9 to 12 were identified by electrospray tandem mass spectrometry to be eight isomers having molecular weight of 367 and a fragmentation pattern indicative of arachidonic acid derivatives containing nitro and hydroxy groups and consistent with the structures of vicinal nitrohydroxyeicosatrienoic acids. These lipids spontaneously released NO (183 +/- 12 nmol NO/15 min/micromol) as detected by head space/chemiluminescence analysis. Mild alkaline hydrolysis of total lipids extracted from bovine cardiac muscle followed by isotopic dilution gas chromatography/mass spectrometry analysis detected basal levels of nitrohydroxyeicosatrienoic acids (6.8 +/- 2.6 ng/g tissue; n = 4). Thus, the oxidation product of NO, NO2, reacts with arachidonic acid to generate biologically active vicinal nitrohydroxyeicosatrienoic acids, which may be important endogenous mediators of vascular relaxation and sGC activation.

Radical dinitroalkane dianions from the nitration of nitroalkanes by peroxynitrite.

In alkaline solutions at pH >10, peroxynitrite (ONOO(-)) rapidly and efficiently nitrates aci-nitroalkane anions, RCH=NO(2)(-) (R = H, CH(3), or CH(3)CH(2)), to give the radical dinitrodianions, RC(NO(2))(2)(2-). These anions have been characterized by EPR and have multiplets based on 1:2:3:2:1 pentets consistent with a hyperfine coupling with two equivalent (14)N nuclei of the nitro groups, and the following hyperfine coupling constants, in gauss: R = H, a(N) = 9.96 and a(H) = 1.85; R = CH(3), a(N) = 9.90 and a(H) = 3.22; and R = CH(3)CH(2), a(N) = 9.57 and a(H) = 4.01. Nitration is attributed to the trapping of nitrogen dioxide, formed by ONO-OCO(2)(-) homolysis for the carbon dioxide adduct of peroxynitrite, by the aci-nitroalkane anion. In air, the radical dinitrodianions are oxidized to the monoanions, and the kinetics of its formation is readily followed by UV/vis spectroscopy of the rise in absorption at 380 nm. This report represents the first successful spin trapping of nitrogen dioxide formed from peroxynitrite, and the method may be a useful one for preparing geminal dinitroalkanes.

On-line synthesis of [11C]nitroalkanes.

The on-line synthesis of 1-11C-labelled nitroalkanes [nitromethane (I), nitroethane (II) and nitropropane (III)], from their corresponding 1-11C-labelled alkyl iodides, by use of a heated silver nitrite column is described. The radiochemical yields of I, II and III were of the order of 40-70%, based on the corresponding [1-11C]alkyl iodides. The total radiochemical yields, starting from [11C]carbon dioxide, were of the order of 25-55% with an overall synthesis time of 8-15 min.