Single-step formation of structurally defined bicyclic peptides via S(N)Ar cyclization

[structure: see text]. A solid-phase methodology for macrocyclization via an S(N)Ar reaction has been developed for the unambiguous formation of bicyclic peptidic compounds in a single cyclization step. The cyclization strategy involves the reaction of a 3,5-dihydroxybenzoyl group with two nitrofluorobenzoyl moieties. The symmetry of the dihydroxy aromatic ring results in a single product, and the remaining nitro groups are subsequently reduced to anilines and acylated.     

Catalytic deoxygenation of organic compounds by carbon monoxide: III. The reaction under pressure of aromatic nitro compounds in the presence of o-phthalaldehyde

The reaction of o-phthalaldehyde with several aromatic nitro compounds in the presence of carbon monoxide and catalytic quantities of hexarhodium-hexadecacarbonyl eventuated in the formation of the corresponding N-substituted isoindolinone as the major product. A reaction mechanism has been suggested incorporating deoxygenation of the nitro compound by carbon monoxide to a nitrene intermediate and the subsequent interception of the latter by o-phthalaldehyde.     

A Facile One‐Step Synthesis of 2‐Arylindazoles via Reductive Cyclization of N‐(2‐nitroarylidene)amines

A mild and efficient synthesis of 2‐arylindazole derivatives via the reductive cyclization of nitro‐aryl substrates mediated by a low‐valent titanium reagent (TiCl₄/Sm/Et₃N) has been developed. The attractive features of the current method include an N–N bond formation and the selective reduction of the C = N bond and nitro group, both of which were easily achieved in one‐pot by controlling the pH of the reaction mixture.     

Kinetics of the liquid-phase catalytic hydrogenation of chlorine-containing aromatic nitro compounds in the presence of pyridine

We have analyzed experimental kinetic data for nitro compound consumption, for the formation of the corresponding amino product, and for the accumulation of intermediate products and by-products in the hydrogenation of chlorine-containing aromatic nitro compounds. The reaction has been carried out under static conditions over a platinum catalyst on a porous support in the presence of pyridine. The effect of the admixture on different hydrogenation steps of a chlorine-containing aromatic nitro compound has been quantitatively interpreted.     

Nitropyrazoles 21. Selective nucleophilic substitution of the nitro group in 1-amino-3,4-dinitropyrazole

Nucleophilic substitution of the nitro group in a model representative of N-aminopyrazoles, 1-amino-3,4-dinitropyrazole, has been studied for the first time. The compound was shown to undergo nucleophilic substitution with S-nucleophiles. The reaction was effected with regioselective substitution of the nitro group at position 3 and in good yields.     

Chemical modification of silica surfaces

The formation of phenylaerosil via silica hydride in the gas phase and the subsequent introduction of nitro and amino groups in solution has been followed using IR and UV spectroscopy. The direct reaction of aminophenyltriethoxysilane (APhS) with the silica surface has also been investigated.     

Intermolecular cross-double-michael addition between nitro and carbonyl activated olefins as a new approach in C-C bond formation

A novel intermolecular cross-double-Michael addition between nitro and carbonyl activated olefins has been developed through Lewis base catalysis. The reaction took place with a large group of beta-alkyl nitroalkenes and alpha,beta-unsaturated ketone/esters, producing an allylic nitro compound in good to excellent yields.     

Catalyst‐Free Reductive Coupling of Aromatic and Aliphatic Nitro Compounds with Organohalides

A rare reductive coupling of nitro compounds with organohalides has been realized. The reaction is initiated by a partial reduction of the nitro group to a nitrenoid intermediate. Therefore, not only aromatic but also aliphatic nitro compounds are efficiently transformed into monoalkylated amines, with organohalides as the alkylating agent. Given the innate reactivity of the nitrenoid, a catalyst is not required, resulting in a high tolerance for aryl halide substituents in both starting materials.     

Reduction of 2-amino-3- and -5-nitropyridine derivatives with hydrazine hydrate

The reactions of 2-amino-3-nitropyridine and 2-amino-5-nitropyridine with hydrazine hydrate resulted in elimination of the amino group and reduction of the nitro group with formation of 3-aminopyridine. A probable reaction mechanism involves addition of hydrazine hydrate at the N-C² bond, followed by elimination of ammonia and reduction of the nitro group to amino. 2-Amino-4-methyl-3-nitropyridine and 2-amino-5-methyl-3-nitropyridine reacted with hydrazine hydrate in a similar way.     

One-step double reduction of aryl nitro and carbonyl groups using hydrazine

Single-step reduction of aryl nitro and carbonyl groups to the corresponding synthetically useful alkyl-anilines occurs with excellent yields by treatment with hydrazine and a base in a solvent-free reaction. The method has been applied to a broad range of compounds with different properties. Investigations into the mechanism of the reduction reveal that each group is reduced independently. A mechanism is proposed for this novel reduction of aromatic nitro groups.     

‘On water’ synthesis of 2,4-diaryl-2,3-dihydro-1,5-benzothiazepines catalysed by sodium dodecyl sulfate (SDS)

An efficient synthesis of 1,3-diaryl-2,3-dihydro-1,5-benzothiazepines has been developed by the reaction of various 1,3-diaryl-2-propenones with 2-aminothiophenol in water under neutral conditions catalysed by SDS. Excellent chemoselectivity was observed for substrates possessing halogen atoms or nitro/alkoxy/thioalkyl groups which did not undergo competitive aromatic nucleophilic substitution of the halogen atoms or the nitro group, reduction of the nitro or the α,β-unsaturated carbonyl group, or dealkylation of the alkoxy/thioalkoxy groups.     

Theoretical study of the decomposition reactions in substituted nitrobenzenes

The influence of substituent nature and position on the unimolecular decomposition of nitroaromatic compounds was investigated using the density functional theory at a PBE0/6-31+G(d,p) level. As the starting point, the two main reaction paths for the decomposition of nitrobenzene were analyzed: the direct carbon nitrogen dissociation (C6H5 + NO2) and a two step mechanism leading to the formation of phenoxyl and nitro radicals (C6H5O + NO). The dissociation energy of the former reaction was calculated to be 7.5 kcal/mol lower than the activation energy of the second reaction. Then the Gibbs free energies were computed for 15 nitrobenzene derivatives characterized by different substituents (nitro, methyl, amino, carboxylic acid, and hydroxyl) in the ortho, meta, and para positions. In meta position, no significant changes appeared in the reaction energy profiles whereas ortho and para substitutions led to significant deviations in energies on the decomposition mechanisms due to the resonance effect of the nitro group without changing the competition between these mechanisms. In the case of para and meta substitutions, the carbon-nitro bond dissociation energy has been directly related to the Hammett constant as an indicator of the electron donor-acceptor effect of substituents.     

6(5H)-phenanthridinones. II. Preparation of substituted 6(5h)-phenanthridinones from 9-oxofluorenes

A number of 6(5H)-phenanthridinones have been conveniently prepared from 9-oxofluorenes through the Schmidt reaction. It has been found that all amino and nitro 9-oxofluorenes thus far tried gave substituted 6(5H)-phenanthridinones with the amino or nitro group situated in the benzene ring attached to the nitrogen of the lactam group. UV and IR spectral data are presented for these compounds.     

New nitronate sigma complexes and the mechanism of nucleophilic aromatic photosubstitution para to a nitro group

[reaction: see text] Photolysis of 4-nitroanisole with aliphatic amines gives mainly N-substituted 4-nitroanilines. Reactions of this type have been widely attributed to a geminate radical mechanism. We questioned this interpretation and have searched for and found by NMR spectroscopy a new class of stable nitronate adducts generated under the reaction conditions. The adducts imply that photosubstitution by amines para to the nitro group occurs by meta sigma complex formation followed by an unprecedented sigmatropic rearrangement.     

Organocatalytic enantioselective synthesis of highly functionalized polysubstituted pyrrolidines

The organocatalytic conjugate addition of different aldehydes to beta-nitroacrolein dimethyl acetal, generating the corresponding highly functionalized nitroaldehydes in high yields and with high stereoselectivities, has been studied in detail. These transformations have been achieved by using both readily available starting materials in a 1:1 ratio as well as commercially available catalysts at a 10 mol % catalyst loading. Furthermore, a very short and efficient protocol has been devised for the preparation of highly enantioenriched pyrrolidines containing two or three contiguous stereocenters starting from the obtained Michael adducts. 3,4-Disubstituted pyrrolidines have been obtained in a single step by Zn-mediated chemoselective reduction of the nitro group followed by intramolecular reductive amination, and trisubstituted homoproline derivatives have been prepared by means of an olefination reaction and a cascade process involving chemoselective reduction of the nitro group followed by a fully diastereoselective intramolecular aza- Michael reaction.     

Synthesis of Spiropyrazolines via a Pseudo‐Six Component Reaction

A novel and eco‐friendly route for the synthesis of highly functionalized spiropyrazolines via a pseudo‐six component reaction of hydrazine hydrate, nitro ketene dithioacetal, isatin, and active methylene under mild condition at room temperature in ethanol media has been developed. The key steps in the synthetic strategy involve the formation of 1,1‐dihydrazino‐2‐nitroethylene from hydrazine hydrate with nitro ketene dithioacetal and its reaction with Knoevenagel adduct derived from the corresponding isatin and active methylene. The reaction is particularly attractive due to features such as high bond‐forming efficiency, optimum convergence, mild condition, atom economy, easy work‐up/purification, and reduced waste production without using any additive.     

Intramolecular condensation of nitro group with olefinic double bond

Conclusions A new reaction of nitro compounds was discovered on the example of the thermal isomerization of unsaturated nitrocarbinols and nitrodihydropyrans, consisting in the intramolecular addition of the nitro group to the olefinic double bond with the formation of the heterolytic 1,3,2-dioxazoline system.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 2, pp. 370–378, February, 1968.     

Reactions of organic anions—L : Reactions of phenylacetonitrile derivatives with aromatic nitrocompounds in basic media

Reaction of phenylalkanenitriles and diphenylacetonitrile with aromatic nitro compounds were studied using various base-solvent systems. Four independent types of reaction: substitution of halogen, substitution of nitro group, substitution of hydride anion and electron transfer were observed. Relationship—reaction pathway—conditions have been discussed.     

Organocatalytic asymmetric michael addition of aldehydes to beta-nitroacroleine dimethyl acetal

[Structure: see text] The organocatalytic asymmetric Michael addition of aldehydes to beta-nitroacroleine dimethyl acetal has been studied in detail. The reaction took place with excellent yields and high stereoselectivities when a chiral beta-amino alcohol such as L-prolinol was employed as the catalyst, leaving a formation of highly functionalized enantioenriched compounds containing two differentiated formyl groups together with a nitro moiety.     

High‐Yielding Synthesis of the Anti‐Influenza Neuraminidase Inhibitor (−)‐Oseltamivir by Two “One‐Pot” Sequences

The efficient asymmetric total synthesis of (?)‐oseltamivir, an antiviral reagent, has been accomplished by using two “one‐pot” reaction sequences, with excellent overall yield (60 %) and only one required purification by column chromatography. The first one‐pot reaction sequence consists of a diphenylprolinol silyl ether mediated asymmetric Michael reaction, a domino Michael reaction/Horner–Wadsworth–Emmons reaction combined with retro‐aldol/Horner–Wadsworth–Emmons reaction and retro Michael reactions, a thiol Michael reaction, and a base‐catalyzed isomerization. Six reactions can be successfully conducted in the second one‐pot reaction sequence; these are deprotection of a tert‐butyl ester and its conversion into an acyl chloride then an acyl azide, Curtius rearrangement, amide formation, reduction of a nitro group into an amine, and a retro Michael reaction of a thiol moiety. A column‐free synthesis of (?)‐oseltamivir has also been established.