Draft:Anomeric amide
 | Draft article not currently submitted for review.
This is a draft Articles for creation (AfC) submission. It is not currently pending review. While there are no deadlines, abandoned drafts may be deleted after six months. To edit the draft click on the "Edit" tab at the top of the window. To be accepted, a draft should:
It is strongly discouraged to write about yourself, your business or employer. If you do so, you must declare it. Where to get help
How to improve a draft
You can also browse Wikipedia:Featured articles and Wikipedia:Good articles to find examples of Wikipedia's best writing on topics similar to your proposed article. Improving your odds of a speedy review To improve your odds of a faster review, tag your draft with relevant WikiProject tags using the button below. This will let reviewers know a new draft has been submitted in their area of interest. For instance, if you wrote about a female astronomer, you would want to add the Biography, Astronomy, and Women scientists tags. Editor resources
Last edited by CanadianPeninsula (talk | contribs) 0 seconds ago. (Update) |
In organic chemistry, anomeric amides refer to amides connected to two heteroatoms at the amide nitrogen atom, typically two oxygen atoms or an oxygen atom and a halogen atom. Much like acetals and aminals, the nitrogen atom experiences anomeric effect from the heteroatoms. Anomeric amides exhibit different reactivities to regular amides — in particular, the amide nitrogen center is a much higher sp3 character, and in combination with the electron-withdrawing substituents resulst in an electrophilic and mildly oxidizing character.[1][2][3]
Introduction
[edit]Anomeric amides are amides with electron-withdrawing substituents on the amide nitrogen atom, with common types including N-alkoxy-N-haloamides, N,N-dialkoxyamides, N-acyloxy-N-alkoxy amides, and N,N-dihaloamides.[1] They were investigated in the late 1980s by Rudchenko and Glover, with Rudchenko exploring N-alkoxy-N-chloroureas and N,N-dialkoxyureas, and Glover investigating N,N-dialkoxyamides and N-acyloxy-N-alkoxyamides. There have been other reports of other anomeric amides earlier than the 1980s, as well as several reports with the amide nitrogen atom connected to one nitrogen atom and one oxygen atom, mostly in the the form of N,N'-dialkoxy-N,N'-diacylhydrazines.
Structure and Bonding
[edit]Anomeric amides exhibit a much greater sp3 character at the amide nitrogen atom, in contrast to the typical sp2 character of a classical amide functional group. This is due to the electron-withdrawing substituents on the amide nitrogen, pulling electron density away from the nitrogen atom and diminishing the electron density donated from the nitrogen atom into the carbonyl group. Additionally, the substituents also induce and experience anomeric effect on each other, with the lone pair of the substituents donating into the σ* of the adjacent substituent.
With a significant enough electron-withdrawing group in place of the acyl substituent, the polarity of the N-substituent bond can be reversed. For instance, sulfonamide analogs of anomeric amides have shown the
Synthesis
[edit]Reactions
[edit]HERON
[edit]Nitrogen Deletion
[edit]Anomeric amides have been shown to form isodiazenes with primary and secondary amines. For secondary isodiazenes, the molecule is able to expel nitrogen gas, forming a diradical species which can undergo recombination, allowing for nitrogen deletion-type molecular editing.[6] For primary isodiazenes, the nitrogen expulsion occurs after hydrogen atom transfer, and generates a carbon-centered radical, allowing for protodeamination;[7] as well as broader deaminative radical transformations such as halogenation, hydroxylation, phosphonylation, thiolation,[8] and trifluoromethylation.[9]
Halogenation
[edit]Halogenated anomeric amides have been shown to perform halogenation as an electrophilic halide source, with the rehybridization of the amide from sp2 to sp3 being the driving force.[10]
Nitrene precursor
[edit]Anomeric amides are also capable of acting as a nitrene surrogate.[11]
Other reactions
[edit]Anomeric amides have been shown to react with pyridines to form N-alkoxy-N-(1-pyridinium)urea salts.[12]
Anomeric amides have also been shown to convert thiols to disulfides.[13]
Toxicity
[edit]Due to the electrophilic N-center of anomeric amides, they are suscpetible to nucleophilic attack. Studies have shown that N-acyloxy-N-alkoxyamides can be potential mutagens, as they could act as an elecctrophile to the nucleophilic sites on DNA.[14]
References
[edit]- ^ a b Glover, Stephen A. (1998). "Anomeric amides — Structure, properties and reactivity". Tetrahedron. 54 (26): 7229–7271. doi:10.1016/S0040-4020(98)00197-5.
- ^ Glover, Stephen A.; Rosser, Adam A. (2014). "HERON reactions of anomeric amides: understanding the driving force". Journal of Physical Organic Chemistry. 28 (3): 215–222. doi:10.1002/poc.3322.
- ^ Glover, Stephen A.; Rosser, Adam A. (2018). "Heteroatom Substitution at Amide Nitrogen—Resonance Reduction and HERON Reactions of Anomeric Amides". Molecules. 23 (11): 2834. doi:10.3390/molecules23112834. PMC 6278557. PMID 30384496.
- ^ Glover, Stephen A.; White, Jonathan M.; Rosser, Adam A.; Digianantonio, Katherine M. (2011). "Structures of N,N-Dialkoxyamides: Pyramidal Anomeric Amides with Low Amidicity". The Journal of Organic Chemistry. 76 (23): 9757–9763. doi:10.1021/jo201856u.
- ^ Berger, Kathleen J.; Dherange, Balu D.; Morales, Megan; Driscoll, Julia L.; Tarhan, A. Kaan; Levin, Mark D. (2023). "N-(Benzyloxy)-N-(pivaloyloxy)-4-(trifluoromethyl)-benzamide". Organic Syntheses. 100: 113–135. doi:10.15227/orgsyn.100.0113.
- ^ Kennedy, Sean H.; Dherange, Balu D.; Berger, Kathleen J.; Levin, Mark D. (2021). "Skeletal editing through direct nitrogen deletion of secondary amines". Nature. 593 (7858): 223–227. Bibcode:2021Natur.593..223K. doi:10.1038/s41586-021-03448-9. PMID 33981048.
- ^ Berger, Kathleen J.; Driscoll, Julia L.; Yuan, Mingbin; Dherange, Balu D.; Gutierrez, Osvaldo; Levin, Mark D. (2021). "Direct Deamination of Primary Amines via Isodiazene Intermediates". Journal of the American Chemical Society. 143 (42): 17366–17373. doi:10.1021/jacs.1c09779.
- ^ Dherange, Balu D.; Yuan, Mingbin; Kelly, Christopher B.; Reiher, Christopher A.; Grosanu, Cristina; Berger, Kathleen J.; Gutierrez, Osvaldo; Levin, Mark D. (2023). "Direct Deaminative Functionalization". Journal of the American Chemical Society. 145 (1): 17–24. doi:10.1021/jacs.2c11453.
- ^ Xue, Jiang-Hao; Li, Yin; Liu, Yuan; Li, Qingjiang; Wang, Honggen (2024). "Site-Specific Deaminative Trifluoromethylation of Aliphatic Primary Amines". Angewandte Chemie International Edition. 63 (8): e202319030. doi:10.1002/anie.202319030.
- ^ Wang, Yu; Bi, Cheng; Kawamata, Yu; Grant, Lauren N.; Samp, Lacey; Richardson, Paul F.; Zhang, Shasha; Harper, Kaid C.; Palkowitz, Maximilian D.; Vasilopoulos, Aristidis; Collins, Michael R.; Oderinde, Martins S.; Tyrol, Chet C.; Chen, Doris; LaChapelle, Erik A.; Bailey, Jake B.; Qiao, Jennifer X.; Baran, Phil S. (2024). "Discovery of N–X anomeric amides as electrophilic halogenation reagents". Nature Chemistry. 16 (9): 1530–1545. Bibcode:2024NatCh..16.1539W. doi:10.1038/s41557-024-01539-4. PMID 38769366.
- ^ Stein, Colin; Tyler, Jasper L.; Wiener, Julius; Boser, Florian; Daniliuc, Constantin G.; Glorius, Frank (2024). "Anomeric Amide-Enabled Alkene-Arene and Alkene-Alkene Aminative Coupling". Angewandte Chemie International Edition: e202418141. doi:10.1002/anie.202418141.
- ^ Shtamburg, Vasiliy G.; Shishkin, Oleg V.; Zubatyuk, Roman I.; Kravchenko, Svetlana V.; Tsygankov, Alexander V.; Shtamburg, Victor V.; Distanov, Vitaliy B.; Kostyanovsky, Remir G. (2007). "Synthesis, structure and properties of N-alkoxy-N-(1-pyridinium)urea salts, N-alkoxy-N-acyloxyureas and N,N-dialkoxyureas". Mendeleev Communications. 17 (3): 178–180. doi:10.1016/j.mencom.2007.05.016.
- ^ Xu, Xiaobo; Yan, Leyu; Huang, Weijie; Wang, Yanping; Wang, Mengya; Feng, Liming; Wang, Panpan; Wang, Shengqiang (2024). "Facile and efficient transformation of thiols to disulfides via a radical pathway with N-anomeric amide". RSC Advances (14): 17780–17784. doi:10.1039/D4RA03545C.
- ^ Glover, Stephen A. (2022). "Mutagenicity of N-acyloxy-N-alkoxyamides – QSAR determination of factors controlling activity". Australian Journal of Chemistry. 78 (1): 1–24. doi:10.1071/CH22205.