Synthesis of α-Nitro Carbonyls via Nitrations in Flow

Chentsova, Anna; Ushakov, Dmitry B.; Seeberger, Peter H.; Gilmore, Kerry

doi:10.1021/acs.joc.6b01634

Cited by 11 publications

(7 citation statements)

References 68 publications

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“…When applied to a potentially hazardous nitroalkane, the concentration and isolation steps become no less important than the safety of the chemical reaction itself, even on a relatively small scale. Approaches that minimize nitroalkane quantities through a continuous recycle have been published, but no examples exist that detail the synthesis and immediate reaction of nitroalkanes. A general safety assessment and the development of an innovative strategy to provide comprehensive solutions to these challenges are therefore highly valuable.…”

Section: Introductionmentioning

confidence: 99%

Continuous Platform To Generate Nitroalkanes On-Demand (in Situ) Using Peracetic Acid-Mediated Oxidation in a PFA Pipes-in-Series Reactor

Tsukanov

Johnson

May

et al. 2018

Org. Process Res. Dev.

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The synthetic utility of the aza-Henry reaction can be diminished on scale by potential hazards associated with the use of peracid to prepare nitroalkane substrates, and the nitroalkanes themselves. In response, a continuous and scalable chemistry platform to prepare aliphatic nitroalkanes on-demand is reported, using the oxidation of oximes with peracetic acid and direct reaction of the nitroalkane intermediate in an aza-Henry reaction. A uniquely designed pipes-in-series plug flow tube reactor addresses a range of process challenges including stability and safe handling of peroxides and nitroalkanes. The subsequent continuous extraction generates a solution of purified nitroalkane which can be directly used in the following enantioselective aza-Henry chemistry to furnish valuable chiral diamine precursors in high selectivity, thus, completely avoiding isolation of potentially unsafe low molecular weight nitroalkane intermediate. A continuous campaign (16 h) established that these conditions were effective in processing 100 g of the oxime and furnishing 1.4 L of nitroalkane solution.

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Section: Introductionmentioning

confidence: 99%

Continuous Platform To Generate Nitroalkanes On-Demand (in Situ) Using Peracetic Acid-Mediated Oxidation in a PFA Pipes-in-Series Reactor

Tsukanov

Johnson

May

et al. 2018

Org. Process Res. Dev.

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“…Herein, we describe the realization of this process, which offers a regioselective route to install 1,2‐nitro alcohols (Scheme b). Noteworthy advantages of this protocol are as follows: (a) good regioselectivity; (b) base‐ and metal‐free; (c) the abundance and accessibility of nitration and hydroxylation reagents; (d) the synthetically valuable of desired oxynitration products …”

Section: Methodsmentioning

confidence: 99%

Metal‐Free Regioselective Oxynitration of Acrylamides: Synthesis of 1,2‐Nitro Alcohols

et al. 2019

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A metal-free oxynitration of acrylamides with commercially available tert-butyl nitrite and easily available air was achieved through a regioselective pathway. A wide range of 1,2-nitro alcohols were thus efficiently synthesized in a novel route under mild conditions. The reaction involves a radical process, allows a highly regioselective strategy toward the formation of new CÀ N and CÀ O bonds in one step.

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“…138 Under more severe reaction conditions, the deacetylation process may occur (Scheme 63c), 139 although such reactivity is more typical for the nitration in a mixture of sulfuric and nitric acids. 140 It is of note that acyl nitrate can react with saturated aliphatic compounds, although this is not a nitration reaction. 141 In the presence of chlorotrimethylsilane/acetyl nitrate mixture, nitryl chloride can be generated and used in the one-pot synthesis of gem-chloronitro compounds from oximes.…”

Section: Special Topic Synthesismentioning

confidence: 99%

Organic Nitrating Reagents

Patra¹,

Mosiagin²,

Katayev³

et al. 2022

Synthesis

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Nitro compounds are vital raw chemicals that are widely used in academic laboratories and industries for the preparation of various drugs, agrochemicals, and materials. Thus, nitrating reactions are of great importance for chemists and are even taught in schools as one of the fundamental transformations in organic synthesis. Since the discovery of the first nitrating reactions in the 19th century, progress in this field has been constant. Yet, for many years the classical electrophilic nitration approach using a mixture of strong mineral acids dominated the field. However, in recent decades, the attention of researchers has focused on new reactivity and new reagents that can provide access to nitro compounds in a practical and straightforward way under mild reaction conditions. Organic nitrating reagents have played a special role in this field since they have enhanced reactivity. They also allow nitration to be carried out in an ecofriendly and sustainable manner. This review examines the development and application of organic nitrating reagents.1 Introduction2 Organic Nitrating Reagents2.1 Alkyl Nitrites2.2 Nitroalkanes2.3 Alkyl Nitrates2.4 N-Nitroamides2.5 N-Nitropyrazole2.6 N-Nitropyridinium Salts3 Organic Nitrating Reagents Generated In Situ3.1 Acyl Nitrates3.2 Trimethylsilyl Nitrate3.3 Nitro Onium Salts4 Organic Nitronium Salts5 Organic Nitrates and Nitrites5.1 Ammonium Nitrates5.2 Heteroarylium Nitrates5.3 Other Organic Nitrates5.4 Organic Nitrites6 Conclusion and Outlook

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Synthesis of α-Nitro Carbonyls via Nitrations in Flow

Cited by 11 publications

References 68 publications

Continuous Platform To Generate Nitroalkanes On-Demand (in Situ) Using Peracetic Acid-Mediated Oxidation in a PFA Pipes-in-Series Reactor

Continuous Platform To Generate Nitroalkanes On-Demand (in Situ) Using Peracetic Acid-Mediated Oxidation in a PFA Pipes-in-Series Reactor

Metal‐Free Regioselective Oxynitration of Acrylamides: Synthesis of 1,2‐Nitro Alcohols

Organic Nitrating Reagents

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