AcOH-catalyzed aza-Michael addition/N-nitrosation: An efficient approach to CF2HCH2-containing N-nitrosoamines

Wang, Jianshu; Shan, Jing; Bai, Ming; Cui, Bao‐Dong; Wan, Nan‐Wei; Wang, Yun-Si; Han, Wen‐Yong; Chen, Yong‐Zheng

doi:10.1016/j.tet.2018.05.073

Cited by 6 publications

(4 citation statements)

References 85 publications

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“…76 The employment of an organic acid or base in conjunction with alkyl nitrites in organic solvents or solvent-free conditions have been rarely reported. 77,78 3.2.3. Organic Nitro Compounds.…”

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confidence: 99%

Pathways for N-Nitroso Compound Formation: Secondary Amines and Beyond

López‐Rodríguez

McManus

Murphy

et al. 2020

Org. Process Res. Dev.

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Recent drug recalls (e.g., valsartan and ranitidine) linked to the discovery of nitrosamine impurities have led to increased regulatory scrutiny in the manufacturing process of marketed medicines, notably for determining any sources of risk for nitrosamine (or related N-nitroso compound) formation within the manufacturing process. This review seeks to aid the risk assessment process through identifying known conditions and reactants through which N-nitroso compounds can be formed.

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confidence: 99%

Pathways for N-Nitroso Compound Formation: Secondary Amines and Beyond

López‐Rodríguez

McManus

Murphy

et al. 2020

Org. Process Res. Dev.

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“…It should be noted that nitrosamines may not reduce as fast as nitro groups under these conditions, as evidenced by the work of Chen and co-workers, who were able to selectively reduce a nitro group in the presence of a nitrosamine, to produce the corresponding primary amine (Scheme 7). 45 The relatively mild temperature likely played a role in the observed selectivity.…”

Section: ■ Reductive Nitrosamine Chemistrymentioning

confidence: 99%

Nitrosamine Reactivity: A Survey of Reactions and Purge Processes

Borths

Burns

Curran

et al. 2021

Org. Process Res. Dev.

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Drug recalls have led to increased regulatory scrutiny into the formation and presence of nitrosamine (Nnitrosoamine) impurities in medicines. This review aims to assist the development of risk mitigation strategies by summarizing known reactions of nitrosamines, with a focus on reactions useful within the context of complex molecule synthesis. This review should serve as a useful reference and help lead to the development of chemical processes which effectively control nitrosamines.

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“…In order to investigate the reaction, nitroolefins were subjected to the [3 + 2] cycloaddition with in situ generated CF 2 HCHN 2 under our previously reported conditions (Scheme A). However, an unexpected aza-Michael addition/ N -nitrosation process occurred, affording N -(2,2-difluoroethyl)- N -[2-nitro-1-(hetero)arylethyl] nitrous amides (Scheme A) . During the performance of this work, Ma and co-workers developed Ag 2 O-catalyzed one-pot transformation of nitroolefins with in situ generated trifluorodiazoethane (CF 3 CHN 2 ) for the synthesis of 4-substituted 3-trifluoromethyl-1 H -pyrazoles (Scheme B) .…”

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confidence: 99%

“…However, an unexpected aza-Michael addition/N-nitrosation process occurred, affording N-(2,2-difluoroethyl)-N-[2-nitro-1-(hetero)arylethyl] nitrous amides (Scheme 1A). 13 During the performance of this work, Ma and co-workers developed Ag 2 O-catalyzed one-pot transformation of nitroolefins with in situ generated trifluorodiazoethane (CF 3 CHN 2 ) for the synthesis of 4-substituted 3trifluoromethyl-1H-pyrazoles (Scheme 1B). 14 Despite the difference of one fluorine atom, the corresponding pyrazoles bearing a CF 2 H group were not always obtained by substituting CF 2 HCH 2 NH 2 for CF 3 CH 2 NH 2 under the same conditions as Ma reported.…”

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confidence: 99%

Ex Situ Generation of Difluorodiazoethane (CF₂HCHN₂): Application in the Regioselective Synthesis of CF₂H-Containing Pyrazoles

et al. 2019

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A new method for the ex situ generation of difluorodiazoethane (CF2HCHN2) and a procedure for its efficient use in [3 + 2] cycloaddition with nitroolefins by the AcOH/O2 catalyst system were developed by using a simple two-chamber system. The method provides a facile and straightforward access to a series of 4-substituted 5-difluoromethyl-3-nitro-1H-pyrazoles that are of interest in medicinal chemistry. Interestingly, the key factor for the success of this method is the efficient preparation of CF2HCHN2 by an ex situ process.

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AcOH-catalyzed aza-Michael addition/N-nitrosation: An efficient approach to CF2HCH2-containing N-nitrosoamines

Cited by 6 publications

References 85 publications

Pathways for N-Nitroso Compound Formation: Secondary Amines and Beyond

Pathways for N-Nitroso Compound Formation: Secondary Amines and Beyond

Nitrosamine Reactivity: A Survey of Reactions and Purge Processes

Ex Situ Generation of Difluorodiazoethane (CF₂HCHN₂): Application in the Regioselective Synthesis of CF₂H-Containing Pyrazoles

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AcOH-catalyzed aza-Michael addition/N-nitrosation: An efficient approach to CF2HCH2-containing N-nitrosoamines

Cited by 6 publications

References 85 publications

Pathways for N-Nitroso Compound Formation: Secondary Amines and Beyond

Pathways for N-Nitroso Compound Formation: Secondary Amines and Beyond

Nitrosamine Reactivity: A Survey of Reactions and Purge Processes

Ex Situ Generation of Difluorodiazoethane (CF2HCHN2): Application in the Regioselective Synthesis of CF2H-Containing Pyrazoles

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Ex Situ Generation of Difluorodiazoethane (CF₂HCHN₂): Application in the Regioselective Synthesis of CF₂H-Containing Pyrazoles