Α-nitro Ketones Research Articles

Oxidative functionalization of alkylidenecyclopropanes and alkylidenecyclobutanes: a versatile platform to access nitrated cyclopropanes and cyclobutanes.

A divergent radical nitration of alkylidenecyclopropanes (ACPs) and alkylidenecyclobutanes (ACBs) with Fe(NO3)3·9H2O or AgNO2 has been achieved, affording three categories of products including β-nitro alcohol, α-nitro ketone and nitro nitratosation products with yields up to 90%. Particularly, the cyclopropyl and cyclobutyl rings were conserved in the products. The applicability of this method was demonstrated by the scale-up experiment and reduction of the nitro into an amino group. Preliminary mechanistic studies suggested that the nitro radical was involved in the reaction process.

Methods of Synthesis and Antiviral Activity of New 4-Alkyl-3-Nitro-1,4-Dihydroazolo[5,1-c][1,2,4]Triazin-4-ols.

An azo coupling reaction of α-nitro ketones with 5-diazoazoles was used to obtain 4-alkyl-3-nitro-1,4-dihydroazolo[5,1-с][1,2,4]triazines, which were characterized with respect to their antiviral activity against influenza and Coxsackie B3 viruses.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10593-021-02926-2.

Advances in Henry Reaction: A Versatile Method in Organic Synthesis

: Henry reaction is an important reaction employing carbonyls which furnishes β-nitro alcohol, nitroalkene, α-nitro ketones, β-amino alcohol as products and byproducts that may be transfigured as building blocks for other synthetic reactions. This paper focuses on various synthetic routes for Henry reaction, a versatile reaction of high significance in organic synthesis. The paper discusses the chemistry and plausible products of the reaction, along with the various available synthetic routes for the same, ranging from classical conventional methods to modern methods of green chemistry trends. Use of various catalysts as rate enhancer as well as use of various catalysts as enantioselective frontman for stereoselective reactions, have been described in this work.

Synthesis and properties of the salts of 1-nitropropan-2-one and 1-nitrobutan-2-one

A new safe synthesis of α-nitro ketone salts via alkaline hydrolysis of 2-morpholino-1-nitroalkenes has been developed. The salts were introduced into the reactions of diazotization and heterocyclization. Crystal structures of new 2-morpholino-1-nitrobut-1-ene and 6-ethyl-5-nitro-4phenyl-3,4-dihydropyrimidin-2-one have been determined.

Synthetic Approaches to Nitro-Substituted Isoxazoles

Nitro-substituted isoxazoles are of utmost interest both as versatile intermediates for targeted organic synthesis and as perspective bioactive compounds for drug development. Nevertheless, the existing approaches to them usually lack generality and strongly depend on the position of the nitro group and on the presence of other substituents in the isoxazole ring. This review provides the first systematization of all available data concerning synthetic approaches to 3-, 4-, and 5-nitroisoxazoles. There are a number of preparative approaches to 4-nitroisoxazoles based on classical heterocyclization reactions of nitro-substituted compounds and the nitration of isoxazoles. 3-Nitro- and, especially, 5-nitroisoxazoles are much less readily available. A few methods affording 3-nitroisoxazoles have been reported, often employing the heterocyclization of unsaturated compounds by treatment with sodium nitrite. The sole general preparative method for 5-nitroisoxazoles, containing a variety of functional groups, employs the heterocyclization of electrophilic alkenes by treatment with tetranitromethane activated with triethylamine.1 Introduction2 Synthesis of 4-Nitroisoxazoles2.1 Nitration of Isoxazoles2.2 Condensations of α-Nitro Ketones or Their Oximes2.3 1,3-Dipolar Cycloaddition of Nitrile Oxides to Acetylenes and Their Synthetic Equivalents2.4 Heterocyclization of Acetylene Derivatives by Treatment with Sodium Nitrite2.5 Heterocyclization of Nitro Derivatives of 1,3-Diketones and Their Synthetic Equivalents2.6 Miscellaneous Methods3 Synthesis of 3-Nitroisoxazoles3.1 Heterocyclization of Acetylene Derivatives or 1,3-Dihalogenoalkenes by Treatment with Sodium Nitrite3.2 Heterocyclization of Morita–Baylis–Hillman Acetates by Treatment with Sodium Nitrite3.3 1,3-Dipolar Cycloadditions4 Synthesis of 5-Nitroisoxazoles4.1 1,3-Dipolar Cycloadditions4.2 Synthesis Using Polynitro Compounds5 Conclusion

Transition-metal-free α-arylation of nitroketones with diaryliodonium salts for the synthesis of tertiary α-aryl, α-nitro ketones.

Transition-metal-free α-arylation of α-nitroketones with diaryliodonium salts has been realized for the first time. As an application of this methodology, a concise synthesis of the clinical drug tiletamine was also achieved via a three-step procedure from 2-nitrocyclohexanone without the isolation of intermediates.

Ketoreductase catalyzed stereoselective bioreduction of α-nitro ketones.

We report here the stereoselective bioreduction of α-nitro ketones catalyzed by ketoreductases (KREDs) with publicly known sequences. YGL039w and RasADH/SyADH were able to reduce 23 class I substrates (1-aryl-2-nitro-1-ethanone (1)) and ten class II substrates (1-aryloxy-3-nitro-2-propanone (4)) to furnish both enantiomers of the corresponding β-nitro alcohols, with good-to-excellent conversions (up to >99%) and enantioselectivities (up to >99% ee) being achieved in most cases. To the best of our knowledge, KRED-mediated reduction of class II α-nitro ketones (1-aryloxy-3-nitro-2-propanone (4)) is unprecedented. Select β-nitro alcohols, including the synthetic intermediates of bioactive molecules (R)-tembamide, (S)-tembamide, (S)-moprolol, (S)-toliprolol and (S)-propanolol, were stereoselectively synthesized in preparative scale with 42% to 90% isolated yields, showcasing the practical potential of our developed system in organic synthesis. Finally, the advantage of using KREDs with known sequence was demonstrated by whole-cell catalysis, in which β-nitro alcohol (R)-2k, the key synthetic intermediate of hypoglycemic natural product (R)-tembamide, was produced in a space-time yield of 178 g L-1 d-1 as well as 95% ee by employing the whole cells of a recombinant E. coli strain coexpressing RasADH and glucose dehydrogenase as the biocatalyst.

A Facile Synthesis of N-Alkoxyacylimidoyl Halides from α-Nitro Ketones and Alkyl Halides in the Presence of NaHSO4/SiO2

A novel method was developed for the synthesis of N -alkoxyacylimidoyl halide by the reaction of α-nitro ketone and alkyl halides in the presence of NaHSO 4 /SiO 2 . Nitrile oxides that are generated from α-nitro ketones by silica gel supported acid catalysts are the possible intermediate, which react with alkyl halides to form N -alkoxyacylimidoyl halides. Novel 17 N -alkoxyacylimidoyl halides were synthesized by this procedure.

Formation of new C–O and C–N bonds via base promoted Csp2–Csp3 bond cleavage of α-nitro ketone

A catalyst free protocol has been developed for nucleophilic Csp2–Csp3 bond cleavage of α-nitroketone in the presence of potassium carbonate to create new C–O and C–N bonds. A series of different substituted α-nitroketones could be selectively cleaved and converted into corresponding esters and tosylamides in the presence of alcohols and bromamine-T, respectively.

Iridium Diamine Catalyst for the Asymmetric Transfer Hydrogenation of Ketones

A simple and very efficient chiral aqua iridium(III) diamine complex leads to excellent enantioselectivities in the asymmetric transfer hydrogenation of various α-cyano and α-nitro ketones. The catalyst provides the ortho-substituted aromatic alcohols with especially high ee values. The diamine ligands can be used directly as chiral ligands; conversion into the corresponding sulfamide is not necessary.

Organocatalytic asymmetric Michael-type reaction between β,γ-unsaturated α-keto ester and α-nitro ketone

A Michael-type reaction of β,γ-unsaturated α-keto ester and α-nitro ketone was established. With a thiourea catalyst derived from cinchona alkaloid, the reactions afford products in 47-94% yields with 68-96% ee.

Characterization of α-nitromethyl ketone as a new zinc-binding group based on structural analysis of its complex with carboxypeptidase A

Zinc-binding groups (ZBGs) are exhaustively applied in the development of the new inhibitors against a wide variety of physiologically and pathologically important zinc proteases. Here the α-nitro ketone was presented as a new ZBG, which is a transition-state analog featured by the unique bifurcated hydrogen bonds at the active site of carboxypeptidase A based on the structural analysis. Introduction of a nitro group at the α-position of the ketone could provide more non-covalent interactions without loss of the abilities to form a tetrahedral transition-state analog.

Stereoselective anti-Prelog reduction of ketones by whole cells of Comamonas testosteroni in a ‘substrate-coupled’ approach

Lyophilized cells of the open accessible bacterium Comamonas testosteroni DSM 1455 proved to be an excellent catalyst for the asymmetric reduction of different α-azido, α-bromo, and α-nitro ketones at elevated substrate concentrations (16 g/L) in a ‘substrate-coupled’ approach using 20% (v/v) of 2-propanol as hydrogen donor. Excellent anti-Prelog stereoselectivity was obtained, which is less common found in nature.

Facile Regiocontrolled Synthesis of Trialkyl-Substituted Pyrazines

[reaction: see text] Alpha-nitro ketones can be transformed selectively into trialkyl-substituted pyrazines via reaction with alpha-amino ketones using octyl viologen as an electron-transfer reagent. The new synthetic method, and the optimal reaction conditions that allow for the regiochemical control, are described.

α-Nitro Ketone Synthesis Using N-Acylbenzotriazoles

[Reaction: see text]. Readily available N-acylbenzotriazoles 2a-l (derived from a variety of aliphatic, (hetero)aromatic, and N-protected alpha-amino carboxylic acids) smoothly convert primary 3a-c and alpha-functionalized primary nitroalkanes 3d into the corresponding alpha-nitro ketones 5a-p in yields of 39-86% (average 63%).

Alpha-nitro ketone as an electrophile and nucleophile: synthesis of 3-substituted 2-nitromethylenetetrahydrothiophene and -tetrahydrofuran as drosophila nicotinic receptor probes.

3-(6-Chloropyridin-3-yl)methyl-2-nitromethylenetetrahydrothiophene 2 and -tetrahydrofuran 3 were synthesized through novel approaches using alpha-nitro ketone intermediates as an electrophile and nucleophile, respectively. The 2-nitromethylenetetrahydrothiophene 2 was formed exclusively as the Z-isomer through intramolecular attack by a thiol substituent at the carbonyl group of an alpha-nitro ketone, in which the alpha-nitro ketone served as an electrophile. In contrast, the corresponding 2-nitromethylenetetrahydrofuran 3, not accessible by the above route due to limited stability, was prepared as a mixture of E- and Z-isomers by intramolecular attack of the alpha-nitro ketone enol anion in which the deprotonated alpha-nitro ketone served as a nucleophile. These compounds, together with the corresponding 2-nitromethylenepyrrolidine (1), were used to probe the Drosophila neonicotinoid-nicotinic acetylcholine receptor interaction.

Uncatalyzed Conversion of Linear α‐Nitro Ketones into Amides by Reaction with Primary Amines under Solventless Conditions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Uncatalyzed conversion of linear α-nitro ketones into amides by reaction with primary amines under solventless conditions

The reaction of linear α-nitro ketones with primary amines allows the formation of amides through the cleavage of the carbon–carbon bond between the carbonyl group and the carbon-nitro group moiety, promoted by the nucleophilic effect of the amine. The reaction is performed at room temperature, without any catalyst and/or solvent.

Study of the Three‐Component Reaction of α‐Nitrocarbonyl Compounds, Aromatic Aldehydes, and Cyanothioacetamide.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Michael addition of α-nitro ketones to conjugated enones under solventless conditions using silica

Conjugate addition of both linear and cyclic α-nitro ketones to conjugated enones, can be efficiently performed under heterogeneous, solvent-free and mild acidic conditions, by silica. The procedure allows good yields of 2-nitro-1,5-diones and, it worthy of note that no products arising from the cleavage of α-nitro cycloalkanones were observed under these reaction conditions. Moreover, during the work up, the need of extraction with an organic solvent can be avoided since the crude mixture can be directly charged to a chromatography column for immediate purification.