Editing Nitrene

{{short description|Molecule containing a nitrogen atom with four unbonded electrons (:Ṅ·)}}
{{Use dmy dates|date=February 2021}}
[[File:Nitrene triplet.svg|thumb|115px|right|The generic structure of a nitrene group]]

In [[chemistry]], a '''nitrene''' or '''imene''' ({{chem2|R\s:Ṅ*}}) is the [[nitrogen]] analogue of a [[carbene]]. The nitrogen atom is uncharged and [[valence (chemistry)#monovalent|monovalent]],<ref>{{GoldBookRef|file=N04145|title=nitrenes}}</ref> so it has only 6 [[electron]]s in its valence level—two [[covalent bond]]ed and four non-bonded electrons. It is therefore considered an [[electrophile]] due to the [[octet rule|unsatisfied octet]]. A nitrene is a [[reactive intermediate]] and is involved in many [[chemical reaction]]s.<ref>{{cite book|editor-first=W. |editor-last=Lwowski |title=Nitrenes |date=1970 |publisher=Interscience |location=New York}}</ref><ref>{{cite book|first=C. |last=Wentrup |title=Reactive Intermediates |date=1984 |publisher=Wiley |location=New York}}</ref> The simplest nitrene, HN, is called [[imidogen]], and that term is sometimes used as a synonym for the nitrene class.<ref>{{GoldBookRef|file=I02951|title=imidogens}}</ref>

==Electron configuration==
In the simplest case, the linear N–H molecule (imidogen) has its nitrogen atom [[sp hybrid orbital|sp hybridized]], with two of its four non-bonded electrons as a [[lone pair]] in an sp orbital and the other two occupying a [[degenerate orbital|degenerate]] pair of [[p orbitals]]. The [[electron configuration]] is consistent with [[Hund's rule]]: the low energy form is a [[triplet state|triplet]] with one electron in each of the p orbitals and the high energy form is the [[singlet state|singlet]] with an electron pair filling one p orbital and the other p orbital vacant.<ref>{{Citation |last=Vyas |first=Shubham |title=Theory and Computation in the Study of Nitrenes and their Excited-State Photoprecursors |date=2013 |work=Nitrenes and Nitrenium Ions |pages=33–76 |url=https://onlinelibrary.wiley.com/doi/10.1002/9781118560907.ch2 |access-date=2024-12-20 |publisher=John Wiley & Sons, Ltd |language=en |doi=10.1002/9781118560907.ch2 |isbn=978-1-118-56090-7 |last2=Winter |first2=Arthur H. |last3=Hadad |first3=Christopher M.|url-access=subscription }}</ref>

As with carbenes, a strong correlation exists between the [[spin density]] on the nitrogen atom which can be calculated [[in silico]] and the [[zero-field splitting parameter]] ''D'' which can be derived experimentally from [[electron spin resonance]].<ref name=Kvaskoff>{{cite journal|title=Nitrenes, Diradicals, and Ylides. Ring Expansion and Ring Opening in 2-Quinazolylnitrenes|first1=David |last1=Kvaskoff |first2=Paweł |last2=Bednarek |first3=Lisa |last3=George |first4=Kerstin |last4=Waich |first5=Curt |last5=Wentrup |journal=[[J. Org. Chem.]] |date=2006 |volume=71 |issue=11 |pages=4049–4058 |doi=10.1021/jo052541i|pmid=16709043 }}</ref> Small nitrenes such as NH or CF<sub>3</sub>N have D values around 1.8&nbsp;cm<sup>−1</sup> with spin densities close to a maximum value of 2. At the lower end of the scale are molecules with low ''D'' (<&nbsp;0.4) values and spin density of 1.2 to 1.4 such as 9-anthrylnitrene and 9-phenanthrylnitrene.

==Formation==
Because nitrenes are so reactive, they are rarely isolated. Instead, they are formed as reactive intermediates during a reaction. There are two common ways to generate nitrenes:
* From [[azide]]s by [[thermolysis]] or [[photolysis]], with expulsion of [[nitrogen]] gas. This method is analogous to the formation of [[carbene]]s from [[diazo compound]]s.
* From [[isocyanate]]s, with expulsion of [[carbon monoxide]]. This method is analogous to the formation of carbenes from [[ketene]]s.
Since formation of the nitrene typically starts from a diamagnetic precursor, the direct chemical product is a singlet nitrene, which then relaxes to its ground state triplet state. As has been shown for phenylazide as a model system, the direct photoproduct of photochemical-induced N<sub>2</sub> loss can either be the singlet or triplet nitrene.<ref>{{Cite journal |last=Gritsan |first=N. P. |last2=Platz |first2=M. S. |date=2006-09-01 |title=Kinetics, Spectroscopy, and Computational Chemistry of Arylnitrenes |url=https://pubs.acs.org/doi/10.1021/cr040055%2B |journal=Chemical Reviews |volume=106 |issue=9 |pages=3844–3867 |doi=10.1021/cr040055+ |issn=0009-2665|url-access=subscription }}</ref><ref>{{Cite journal |last=Soto |first=Juan |last2=Otero |first2=Juan C. |date=2019-10-24 |title=Conservation of El-Sayed’s Rules in the Photolysis of Phenyl Azide: Two Independent Decomposition Doorways for Alternate Direct Formation of Triplet and Singlet Phenylnitrene |url=https://pubs.acs.org/doi/10.1021/acs.jpca.9b06915 |journal=The Journal of Physical Chemistry A |volume=123 |issue=42 |pages=9053–9060 |doi=10.1021/acs.jpca.9b06915 |issn=1089-5639|url-access=subscription }}</ref><ref>{{Cite journal |last=Domenianni |first=Luis I. |last2=Bauer |first2=Markus |last3=Schmidt-Räntsch |first3=Till |last4=Lindner |first4=Jörg |last5=Schneider |first5=Sven |last6=Vöhringer |first6=Peter |date=2023 |title=Photoinduced Metallonitrene Formation by N2 Elimination from Azide Diradical Ligands |url=https://onlinelibrary.wiley.com/doi/10.1002/anie.202309618 |journal=Angewandte Chemie International Edition |language=en |volume=62 |issue=42 |pages=e202309618 |doi=10.1002/anie.202309618 |issn=1521-3773|doi-access=free }}</ref> By using a triplet sensitizer, the triplet nitrene can also be formed without initial formation of the singlet nitrene.<ref>{{Cite journal |last=Murthy |first=Rajesh S. |last2=Muthukrishnan |first2=Sivaramakrishnan |last3=Rajam |first3=Sridhar |last4=Mandel |first4=Sarah M. |last5=Ault |first5=Bruce S. |last6=Gudmundsdottir |first6=Anna D. |date=2009-01-25 |title=Triplet-sensitized photolysis of alkoxycarbonyl azides in solution and matrices |url=https://linkinghub.elsevier.com/retrieve/pii/S1010603008004346 |journal=Journal of Photochemistry and Photobiology A: Chemistry |volume=201 |issue=2 |pages=157–167 |doi=10.1016/j.jphotochem.2008.10.015 |issn=1010-6030|url-access=subscription }}</ref>

==Isolated Nitrenes==
Although highly reactive, some nitrenes could be isolated and characterized recently.

In 2019, a triplet nitrene was isolated by Betley and Lancaster, stabilized by coordination to a copper center in a bulky ligand.<ref>{{cite journal |author=Carsch, K. M. |author2=DiMucci, I. M. |author3=Iovan, D. A. |author4=Li, A. |author5=Zheng, S.-L. |author6=Titus, C. J. |author7=Lee, S. J. |author8=Irwin, K. D. |author9=Nordlund, D. |author10=Lancaster, K. M. |author11=Betley, T. A. |title=Synthesis of a Copper-Supported Triplet Nitrene Complex Pertinent to Copper-Catalyzed Amination |journal=Science |date=2019 |volume=365 |issue=6458 |pages=1138–1143 |doi=10.1126/science.aax4423 |pmid=31515388 |pmc=7256962 |bibcode=2019Sci...365.1138C }}</ref> Later on, Schneider and coworkers characterized Pd and Pt triplet metallonitrenes, where the organic residue is replaced by a metal.<ref>{{Cite journal |last=Sun |first=Jian |last2=Abbenseth |first2=Josh |last3=Verplancke |first3=Hendrik |last4=Diefenbach |first4=Martin |last5=de Bruin |first5=Bas |last6=Hunger |first6=David |last7=Würtele |first7=Christian |last8=van Slageren |first8=Joris |last9=Holthausen |first9=Max C. |last10=Schneider |first10=Sven |date=November 2020 |title=A platinum(ii) metallonitrene with a triplet ground state |url=https://www.nature.com/articles/s41557-020-0522-4 |journal=Nature Chemistry |language=en |volume=12 |issue=11 |pages=1054–1059 |doi=10.1038/s41557-020-0522-4 |issn=1755-4349|hdl=11245.1/1d9bd22a-92be-40ac-9b3a-e6dc7df2afc9 |hdl-access=free }}</ref><ref>{{Cite journal |last=Schmidt-Räntsch |first=Till |last2=Verplancke |first2=Hendrik |last3=Lienert |first3=Jonas N. |last4=Demeshko |first4=Serhiy |last5=Otte |first5=Matthias |last6=Van Trieste III |first6=Gerard P. |last7=Reid |first7=Kaleb A. |last8=Reibenspies |first8=Joseph H. |last9=Powers |first9=David C. |last10=Holthausen |first10=Max C. |last11=Schneider |first11=Sven |date=2022 |title=Nitrogen Atom Transfer Catalysis by Metallonitrene C−H Insertion: Photocatalytic Amidation of Aldehydes |url=https://onlinelibrary.wiley.com/doi/10.1002/anie.202115626 |journal=Angewandte Chemie International Edition |language=en |volume=61 |issue=9 |pages=e202115626 |doi=10.1002/anie.202115626 |issn=1521-3773 |pmc=9305406 |pmid=34905281}}</ref><ref>{{Cite journal |last=Schmidt-Räntsch |first=Till |last2=Verplancke |first2=Hendrik |last3=Kehl |first3=Annemarie |last4=Sun |first4=Jian |last5=Bennati |first5=Marina |last6=Holthausen |first6=Max C. |last7=Schneider |first7=Sven |date=2024-09-23 |title=C═C Dissociative Imination of Styrenes by a Photogenerated Metallonitrene |url=https://pubs.acs.org/doi/10.1021/jacsau.4c00571 |journal=JACS Au |volume=4 |issue=9 |pages=3421–3426 |doi=10.1021/jacsau.4c00571 |pmc=11423323 |pmid=39328761}}</ref> In 2024, the groups of Beckmann, Ye and Tan reported the isolation and characterization of organic triplet nitrenes, which are protected from chemical reactivity by an extremely bulky ligand.<ref>{{Cite journal |last=Janssen |first=Marvin |last2=Frederichs |first2=Thomas |last3=Olaru |first3=Marian |last4=Lork |first4=Enno |last5=Hupf |first5=Emanuel |last6=Beckmann |first6=Jens |date=2024-07-19 |title=Synthesis of a stable crystalline nitrene |url=https://www.science.org/doi/10.1126/science.adp4963 |journal=Science |volume=385 |issue=6706 |pages=318–321 |doi=10.1126/science.adp4963}}</ref><ref>{{Cite journal |last=Wang |first=Dongmin |last2=Chen |first2=Wang |last3=Chen |first3=Haonan |last4=Chen |first4=Yizhen |last5=Ye |first5=Shengfa |last6=Tan |first6=Gengwen |date=2024-11-19 |title=Isolation and characterization of a triplet nitrene |url=https://www.nature.com/articles/s41557-024-01669-9 |journal=Nature Chemistry |language=en |pages=1–6 |doi=10.1038/s41557-024-01669-9 |issn=1755-4349}}</ref>

==Reactions==
Nitrene reactions include:
* '''Nitrene C–H insertion'''. A nitrene can easily insert into a carbon to hydrogen [[covalent bond]] yielding an amine or amide. A singlet nitrene reacts with [[retention of configuration]]. In one study<ref>{{cite journal|title=Intermolecular Amidation of Unactivated sp<sup>2</sup> and sp<sup>3</sup> C–H Bonds via Palladium-Catalyzed Cascade C–H Activation/Nitrene Insertion |first1=Hung-Yat |last1=Thu |first2=Wing-Yiu |last2=Yu |first3=Chi-Ming |last3=Che |journal=[[J. Am. Chem. Soc.]] |date=2006 |volume=128 |issue=28 |pages=9048–9049 |doi=10.1021/ja062856v|pmid=16834374 }}</ref> a nitrene, formed by oxidation of a [[carbamate]]  with [[potassium persulfate]], gives an [[insertion reaction]] into the [[palladium]] to nitrogen bond of the reaction product of [[palladium(II) acetate]] with [[pyridine|2-phenylpyridine]] to methyl ''N''-(2-pyridylphenyl)carbamate in a [[cascade reaction]]:

::[[File:NitreneAmidation2.png|400px|Nitrene amidation]]

:A nitrene intermediate is suspected in this C–H insertion involving an [[oxime]], [[acetic anhydride]] leading to an [[isoindole]]:<ref>{{cite journal|title=Novel Intramolecular Reactivity of Oximes: Synthesis of Cyclic and Spiro-Fused Imines |first1=Cécile G. |last1=Savarin |first2=Christiane |last2=Grisé |first3=Jerry A. |last3=Murry |first4=Robert A. |last4=Reamer |first5=David L. |last5=Hughes |journal=[[Org. Lett.]] |date=2007 |volume=9 |issue=6 |pages=981–983 |doi=10.1021/ol0630043|pmid=17319674 }}</ref>

::[[File:NitreneOximeReaction.png|400px|Synthesis of cyclic and spiro-fused imines]]

* '''Nitrene cycloaddition'''. With [[alkene]]s, nitrenes react to form [[aziridines]], very often with [[nitrenoid]] precursors such as nosyl- or tosyl-substituted [''N''-(phenylsulfonyl)imino]phenyliodinane (PhI=NNs or PhI=NTs respectively)) but the reaction is known to work directly with the [[Sulfonamide (chemistry)|sulfonamide]] in presence of a [[transition metal]] based [[catalyst]] such as [[copper]], [[palladium]], or [[gold]]:<ref>{{cite journal|title=Nitrene Transfer Reactions Catalyzed by Gold Complexes |first1=Zigang |last1=Li |first2=Xiangyu |last2=Ding |first3=Chuan |last3=He |journal=[[J. Org. Chem.]] |date=2006 |volume=71 |issue=16 |pages=5876–5880 |doi=10.1021/jo060016t|pmid=16872166 |s2cid=43641348 }}</ref><ref>{{cite journal|title=Development of the Copper-Catalyzed Olefin Aziridination Reaction |first1=David A. |last1=Evans |first2=Margaret M. |last2=Faul |first3=Mark T. |last3=Bilodeau |journal=[[J. Am. Chem. Soc.]] |date=1994 |volume=116 |issue=7 |pages=2742–2753 |doi=10.1021/ja00086a007|s2cid=55554519 }}</ref><ref>{{cite journal|title=Mechanistic Studies of Copper-Catalyzed Alkene Aziridination |first1=Peter |last1=Brandt |first2=Mikael J. |last2=Sodergren |first3=Pher G. |last3=Andersson |first4=Per-Ola |last4=Norrby |journal=[[J. Am. Chem. Soc.]] |date=2000 |volume=122 |issue=33 |pages=8013–8020|doi=10.1021/ja993246g|s2cid=98310736 }}</ref><ref>{{cite journal|title=Advances in Nitrogen Transfer Reactions Involving Aziridines |first1=Iain D. G. |last1=Watson |first2=Lily |last2=Yu |first3=Andrei K. |last3=Yudi |journal=[[Acc. Chem. Res.]] |date=2006 |volume=39 |issue=3 |pages=194–206 |doi=10.1021/ar050038m|pmid=16548508 }}</ref><ref>Reactants ''cis''-[[stilbene]] or ''trans''-stilbene, nitrene precursor ''p''-nitrosulfonamide or [[Nosylate|nosylamine]] which is oxidized by [[iodosobenzene diacetate]]. The gold catalyst is based on a [[terpyridine]] tridentate [[ligand]].</ref>

::[[File:NitreneTransferReactionsCatalyzedbyGoldComplexes.png|400px|Nitrene transfer reaction]]

:In most cases, however, [''N''-(''p''-nitrophenylsulfonyl)imino]phenyliodinane (PhI=NNs) is prepared separately as follows:

::[[File:Preparation of PhINNs.png|600px|Preparation of PhINNs]]

:Nitrene transfer takes place next:

::[[File:Copper catalyzed aziridination.png|600px|Nitrene transfer reaction]]

:In this particular reaction both the ''[[cis isomer|cis]]''-[[stilbene]] illustrated and the [[trans isomer|''trans'']] form (not depicted) result in the same ''trans''-aziridine product, suggesting a two-step [[reaction mechanism]]. The energy difference between triplet and singlet nitrenes can be very small in some cases, allowing [[Intersystem crossing|interconversion]] at room temperature. Triplet nitrenes are thermodynamically more stable but react stepwise allowing free rotation and thus producing a mixture of stereochemistry.<ref>{{cite book|title=Aziridines and Epoxides in Organic Synthesis |editor-first=Andrei K. |editor-last=Yudin |date=2007 |page=120 |isbn=978-3-527-31213-9}}</ref>
* '''Arylnitrene ring-expansion and ring-contraction''': Aryl nitrenes show ring expansion to 7-membered ring [[cumulene]]s, ring opening reactions and nitrile formations many times in complex reaction paths. For instance the azide '''2''' in the scheme below<ref name=Kvaskoff /> trapped in an [[argon]] [[Matrix Isolation|matrix]] at 20&nbsp;K on photolysis expels nitrogen to the triplet nitrene '''4''' (observed experimentally with [[electron spin resonance|ESR]] and [[ultraviolet-visible spectroscopy]]) which is in equilibrium with the ring-expansion product '''6'''.

:[[File:NitreneRingContraction.png|400px|Nitrene ring-expansion and ring-contraction]]

:The nitrene ultimately converts to the ring-opened [[nitrile]] '''5''' through the [[diradical]] intermediate '''7'''. In a high-temperature reaction, [[flash vacuum thermolysis|FVT]] at 500–600&nbsp;°C also yields the nitrile '''5''' in 65% yield.<ref>The [[quinazoline]] is prepared from the corresponding bromide and [[sodium azide]]. The azide is in equilibrium with the [[tetrazole]] '''3'''.</ref> Arylnitrene internalization in combination with carbon deletion strategies have been used for aromatic carbon-nitrogen swap to generate [[pyridines]] from phenyl azides.<ref name="Sundberg 1972">{{cite journal |last1=Sundberg |first1=Richard J. |last2=Suter |first2=Stuart R. |last3=Brenner |first3=Martin |title=Photolysis of 0-substituted aryl azides in diethylamine. Formation and autoxidation of 2-diethylamino-1H-azepine intermediates |journal=[[Journal of the American Chemical Society]] |date=1972 |volume=94 |issue=2 |pages=513–520 |doi=10.1021/ja00757a032}}</ref><ref name="Burns 2022">{{cite journal |last1=Patel |first1=Sajan C. |last2=Burns |first2=Noah Z. |title=Conversion of Aryl Azides to Aminopyridines |journal=[[Journal of the American Chemical Society]] |date=2022 |volume=144 |issue=39 |pages=17797–17802 |doi=10.1021/jacs.2c08464}}</ref><ref name="Levin 2023">{{cite journal |last1=Pearson |first1=Tyler J. |last2=Shimazumi |first2=Ryoma |last3=Driscoll |first3=Julia L. |last4=Dherange |first4=Balu D. |last5=Park |first5=Dong-Il |last6=Levin |first6=Mark D. |title=Aromatic nitrogen scanning by <i>ipso</i>-selective nitrene internalization |journal=[[Science_(journal)|Science]] |date=2023 |volume=381 |issue=6665 |pages=1474–1479 |doi=10.1126/science.adj5331|pmc=10910605 }}</ref>

==Nitreno radicals==
For several compounds containing both a nitrene group and a [[free radical]] group an ESR high-spin quartet has been recorded (matrix, cryogenic temperatures). One of these has an [[amine oxide]] radical group incorporated,<ref>{{cite journal|title=Heterospin organic molecules: nitrene–radical linkages |journal=[[Polyhedron (journal)|Polyhedron]] |volume=20 |issue=11–14 |date=30 May 2001 |pages=1647–1652 |first1=Paul M. |last1=Lahti |first2=Burak |last2=Esat |first3=Yi |last3=Liao |first4=Paul |last4=Serwinski |first5=Jiang |last5=Lan |first6=Richard |last6=Walton |doi=10.1016/S0277-5387(01)00667-2}}</ref> another system has a carbon radical group.<ref>{{cite journal|title=2,3,5,6-Tetrafluorophenylnitren-4-yl: Electron Paramagnetic Resonance Spectroscopic Characterization of a Quartet-Ground-State Nitreno Radical |first1=Wolfram |last1=Sander |first2=Dirk |last2=Grote |first3=Simone |last3=Kossmann |first4=Frank |last4=Neese |journal=[[J. Am. Chem. Soc.]] |date=2008 |volume=130 |issue=13 |pages=4396–4403 |doi=10.1021/ja078171s|pmid=18327939 }}</ref>

:[[File:NitreneTriRadical.svg|Nitrene radical]]

In this system one of the nitrogen unpaired electrons is delocalized in the aromatic ring making the compound a σ–σ–π triradical. A [[carbene]] nitrogen radical (imidyl radical) [[resonance structure]] makes a contribution to the total electronic picture.


==References==
{{Reflist}}

{{Authority control}}
{{Functional group}}

[[Category:Reactive intermediates]]
[[Category:Free radicals]]
[[Category:Octet-deficient functional groups]]
[[Category:Nitrogen compounds]]