nitrene

In the simplest case, the linear N–H molecule (imidogen) has its nitrogen atom 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 pair of p orbitals. The electron configuration is consistent with Hund's rule: the low energy form is a triplet with one electron in each of the p orbitals and the high energy form is the singlet with an electron pair filling one p orbital and the other p orbital vacant.{{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 }}

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.{{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 }} Small nitrenes such as NH or CF₃N have D values around 1.8 cm⁻¹ with spin densities close to a maximum value of 2. At the lower end of the scale are molecules with low D (< 0.4) values and spin density of 1.2 to 1.4 such as 9-anthrylnitrene and 9-phenanthrylnitrene.

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 azides by thermolysis or photolysis, with expulsion of nitrogen gas. This method is analogous to the formation of carbenes from diazo compounds.
• From isocyanates, with expulsion of carbon monoxide. This method is analogous to the formation of carbenes from ketenes.

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 N₂ loss can either be the singlet or triplet nitrene.{{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 }}{{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 }}{{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 }} By using a triplet sensitizer, the triplet nitrene can also be formed without initial formation of the singlet nitrene.{{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 }}

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.{{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 }} Later on, Schneider and coworkers characterized Pd and Pt triplet metallonitrenes, where the organic residue is replaced by a metal.{{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 }}{{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}}{{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}} 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.{{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}}{{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}}

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{{cite journal|title=Intermolecular Amidation of Unactivated sp² and sp³ 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 }} 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 2-phenylpyridine to methyl N-(2-pyridylphenyl)carbamate in a cascade reaction:

::File:NitreneAmidation2.png

:A nitrene intermediate is suspected in this C–H insertion involving an oxime, acetic anhydride leading to an isoindole:{{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 }}

::File:NitreneOximeReaction.png

• Nitrene cycloaddition. With alkenes, 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 in presence of a transition metal based catalyst such as copper, palladium, or gold:{{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 }}{{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 }}{{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 }}{{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 }}Reactants cis-stilbene or trans-stilbene, nitrene precursor p-nitrosulfonamide or nosylamine which is oxidized by iodosobenzene diacetate. The gold catalyst is based on a terpyridine tridentate ligand.

::File:NitreneTransferReactionsCatalyzedbyGoldComplexes.png

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

::File:Preparation of PhINNs.png

:Nitrene transfer takes place next:

::File:Copper catalyzed aziridination.png

:In this particular reaction both the cis-stilbene illustrated and the 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 interconversion at room temperature. Triplet nitrenes are thermodynamically more stable but react stepwise allowing free rotation and thus producing a mixture of stereochemistry.{{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}}

• Arylnitrene ring-expansion and ring-contraction: Aryl nitrenes show ring expansion to 7-membered ring cumulenes, ring opening reactions and nitrile formations many times in complex reaction paths. For instance the azide 2 in the scheme below trapped in an argon matrix at 20 K on photolysis expels nitrogen to the triplet nitrene 4 (observed experimentally with ESR and ultraviolet-visible spectroscopy) which is in equilibrium with the ring-expansion product 6.

:File:NitreneRingContraction.png

:The nitrene ultimately converts to the ring-opened nitrile 5 through the diradical intermediate 7. In a high-temperature reaction, FVT at 500–600 °C also yields the nitrile 5 in 65% yield.The quinazoline is prepared from the corresponding bromide and sodium azide. The azide is in equilibrium with the tetrazole 3. Arylnitrene internalization in combination with carbon deletion strategies have been used for aromatic carbon-nitrogen swap to generate pyridines from phenyl azides.{{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}}{{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}}{{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 ipso-selective nitrene internalization |journal=Science |date=2023 |volume=381 |issue=6665 |pages=1474–1479 |doi=10.1126/science.adj5331|pmc=10910605 }}

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,{{cite journal|title=Heterospin organic molecules: nitrene–radical linkages |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}} another system has a carbon radical group.{{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 }}

: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.

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Category:Reactive intermediates

Category:Free radicals

Category:Octet-deficient functional groups

Category:Nitrogen compounds