A Study on the Diazo-Transfer Reaction Using o-Nitrobenzenesulfonyl Azide

Abstract

¹⁵N-Labeled azides have a great potential as practical and effective tags for vibrational probing and hyperpolarized magnetic resonance imaging of biomolecules. They can be synthesized by reaction of primary amines with a ¹⁵N-labeled diazo-transfer reagent. TfNN¹⁵N, a γ-¹⁵N-labeled diazo-transfer reagent, was developed to prepare β-¹⁵N-labeled azides; these are vibrational probes devoid of strong spectral interference by Fermi resonance. To overcome the stability and safety problems associated with TfNN¹⁵N, there is a strong demand for the development of a novel γ-¹⁵N-labeled diazo-transfer reagent. We present a study on the diazo-transfer reaction using o-nitrobenzenesulfonyl azide (o-NsN₃). o-NsNN¹⁵N, a γ-¹⁵N-labeled diazo-transfer reagent, was newly developed and found to be better than TfNN¹⁵N with respect to its physicochemical properties and ease of synthesis. Unlike TfNN¹⁵N, however, o-NsNN¹⁵N was found to afford a mixture of β- and γ-¹⁵N-labeled azides rather than the β-¹⁵N-labeled azide alone. A mechanism for the diazo-transfer reaction of o-NsNN¹⁵N with primary amines is proposed to explain the formation of such isotopomeric mixtures.

Key words

diazo-transfer reagents - sulfonyl azides - nosyl azide - organic azides - ¹⁵N labeling - isotopomerism

Publication History

Received: 21 April 2023

Accepted after revision: 29 September 2023

Accepted Manuscript online:
29 September 2023

Article published online:
30 November 2023

• References and Notes

• 1a Scriven EF. V, Turnbull K. Chem. Rev. 1988; 88: 297
• 1b Organic Azides: Syntheses and Applications . Bräse S, Banert K. Wiley; Chichester: 2010
• 1c Tanimoto H, Kakiuchi K. Nat. Prod. Commun. 2013; 8: 1021
• 1d Intrieri D, Zardi P, Caselli A, Gallo E. Chem. Commun. 2014; 50: 11440
• 1e Song X.-R, Qui Y.-F, Liu X.-Y, Liang Y.-M. Org. Biomol. Chem. 2016; 14: 11317
• 1f Huang D, Yan G. Adv. Synth. Catal. 2017; 359: 1600
• 1g Wu K, Liang Y, Jiao N. Molecules 2016; 21: 352
• 1h Sala R, Loro C, Foschi F, Broggini G. Catalysts 2020; 10: 1173
• 2 Köhn M, Breinbauer R. Angew. Chem. Int. Ed. 2004; 43: 3106
• 3a Kolb HC, Finn MG, Sharpless KB. Angew. Chem. Int. Ed. 2001; 40: 2004
• 3b Gordon CG, Mackey JL, Jewett JC, Sletten EM, Houk KN, Bertozzi CR. J. Am. Chem. Soc. 2012; 134: 9199 ; and references cited therein
• 3c Baskin JM, Prescher JA, Laughlin ST, Agard NJ, Chang PV, Miller IA, Lo A, Codelli JA, Bertozzi CR. Proc. Natl. Acad. Sci. U. S. A. 2007; 104: 16793
• 3d Meng G, Guo T, Ma T, Zhang J, Shen Y, Sharpless KB, Dong J. Nature 2019; 574: 86
• 4a Ma J, Pazos IM, Zhang W, Culik RM, Gai F. Annu. Rev. Phys. Chem. 2015; 66: 357
• 4b Adhikary R, Zimmermann J, Romesberg FE. Chem. Rev. 2017; 117: 1927
• 4c Baiz CR, Błasiak B, Bredenbeck J, Cho M, Choi J.-H, Corcelli SA, Dijkstra AG, Feng C.-J, Garrett-Roe S, Ge N.-H, Hanson-Heine MW. D, Hirst JD, Jansen TL. C, Kwac K, Kubarych KJ, Londergan CH, Maekawa H, Reppert M, Saito S, Roy S, Skinner JL, Stock G, Straub JE, Thielges MC, Tominaga K, Tokmakoff A, Torii H, Wang L, Webb LJ, Zanni MT. Chem. Rev. 2020; 120: 7152
• 5a Oh K.-I, Lee J.-H, Joo C, Han H, Cho M. J. Phys. Chem. B 2008; 112: 10352
• 5b Oh K.-I, Kim W, Joo C, Yoo D.-G, Han H, Hwang G.-S, Cho M. J. Phys. Chem. B 2010; 114: 13021
• 5c Lee K.-K, Park K.-H, Joo C, Kwon H.-J, Han H, Ha J.-H, Park S, Cho M. Chem. Phys. 2012; 396: 23
• 5d Lee K.-K, Park K.-H, Joo C, Kwon H.-J, Jeon J, Jung H.-I, Park S, Han H, Cho M. J. Phys. Chem. B 2012; 116: 5097
• 5e Park JY, Kwon H.-J, Mondal S, Han H, Kwak K, Cho M. Phys. Chem. Chem. Phys. 2020; 22: 19223
• 5f Park JY, Mondal S, Kwon H.-J, Sahu PK, Han H, Kwak K, Cho M. J. Chem. Phys. 2020; 153: 164309
• 6a Ye S, Zaitseva E, Caltabiano G, Schertler GF. X, Sakmar TP, Deupi X, Vogel R. Nature 2010; 464: 1386
• 6b Taskent-Sezgin H, Chung J, Banerjee PS, Nagarajan S, Dyer RB, Carrico I, Raleigh DP. Angew. Chem. Int. Ed. 2010; 49: 7473
• 6c Shi L, Liu X, Shi L, Stinson HT, Rowlette J, Kahl LJ, Evans CR, Zheng C, Dietrich LE. P, Min W. Nat. Methods 2020; 17: 844
• 7 Tipping WJ, Lee M, Serrels A, Brunton VG, Hulme AN. Chem. Soc. Rev. 2016; 45: 2075
• 8a Nydegger MW, Dutta S, Cheatum CM. J. Chem. Phys. 2010; 133: 134506
• 8b Okuda M, Ohta K, Tominaga K. J. Chem. Phys. 2015; 142: 212418
• 8c Zhang J, Wang L, Zhang J, Zhu J, Pan X, Cui Z, Wang J, Fang W, Li Y. J. Phys. Chem. B 2018; 122: 8122
• 9a Gai XS, Fenlon EE, Brewer SH. J. Phys. Chem. B 2010; 114: 7958
• 9b Lipkin JS, Song R, Fenlon EE, Brewer SH. J. Phys. Chem. Lett. 2011; 2: 1672
• 9c Chalyavi F, Schmitz AJ, Fetto NR, Tucker MJ, Brewer SH, Fenlon EE. Phys. Chem. Chem. Phys. 2020; 22: 18007
• 10a Park H, Wang Q. Chem. Sci. 2022; 13: 7378
• 10b Bae J, Zhang G, Park H, Warren WS, Wang Q. Chem. Sci. 2021; 12: 14309
• 10c Park H, Chen J, Dimitrov IE, Park JM, Wang Q. ACS Sens. 2022; 7: 2928
• 10d Shchepin RV, Chekmenev EY. J. Labelled Compd. Radiopharm. 2014; 57: 621
• 10e Nelson SJ, Kurhanewicz J, Vigneron DB, Larson PE. Z, Harzstark AL, Ferrone M, van Criekinge M, Chang JW, Bok R, Park I, Reed G, Carvajal L, Small EJ, Munster P, Weinberg VK, Ardenkjaer-Larsen JH, Chen AP, Hurd RE, Odegardstuen L.-I, Robb FJ, Tropp J, Murray JA. Sci. Transl. Med. 2013; 5: 198ra108
• 11a Pandiakumar AK, Sarma SP, Samuelson AG. Tetrahedron Lett. 2014; 55: 2917
• 11b Stevens MY, Sawant RT, Odell LR. J. Org. Chem. 2014; 79: 4826
• 12a Alper PB, Hung S.-C, Wong C.-H. Tetrahedron Lett. 1996; 37: 6029
• 12b Nyffeler PT, Liang C.-H, Koeller KM, Wong C.-H. J. Am. Chem. Soc. 2002; 124: 10773
• 13 Kwon H.-J, Gwak S, Park JY, Cho M, Han H. ACS Omega 2022; 7: 293
• 14a Xie S, Yan Z, Li Y, Song Q, Ma M. J. Org. Chem. 2018; 83: 10916
• 14b Green SP, Payne AD, Wheelhouse KM, Hallett JP, Miller PW, Bull JA. J. Org. Chem. 2019; 84: 5893
• 14c Green SP, Wheelhouse KM, Payne AD, Hallett JP, Miller PW, Bull JA. Org. Process Res. Dev. 2020; 24: 67
• 15a Goddard-Borger ED, Stick RV. Org. Lett. 2007; 9: 3797
• 15b Fischer N, Goddard-Borger ED, Greiner R, Klapötke TM, Skelton BW, Stierstorfer J. J. Org. Chem. 2012; 77: 1760
• 15c Potter GT, Jayson GC, Miller GJ, Gardiner JM. J. Org. Chem. 2016; 81: 3443
• 16a Ye H, Liu R, Li D, Liu Y, Yuan H, Guo W, Zhou L, Cao X, Tian H, Shen J, Wang PG. Org. Lett. 2013; 15: 18
• 16b Beaudoin S, Kinsey KE, Burns JF. J. Org. Chem. 2003; 68: 115
• 17 Barrow AS, Moses JE. Synlett 2016; 27: 1840
• 18a Besenyei G, Párkányi L, Foch I, Simándi LI, Kálmán A. J. Chem. Soc., Perkin Trans. 2 2000; 1798
• 18b Vogt H, Baumann T, Nieger M, Bräse S. Eur. J. Org. Chem. 2006; 5315
• 18c McGorry RJ, Allen SK, Pitzen MD, Coombs TC. Tetrahedron Lett. 2017; 58: 4623
• 19a Candeias NR, Afonso CA. M. Curr. Org. Chem. 2009; 13: 763
• 19b Kim SH, Park SH, Choi JH, Chang S. Chem. Asian J. 2011; 6: 2618
• 19c Zhang Z, Wang S, Zhang Y, Zhang G. J. Org. Chem. 2019; 84: 3919
• 20 o-, m-, and p-Nitrobenzenesulfonyl Azides; General ProcedureA solution of NaN₃ (1.48 g, 22.8 mmol) in H₂O (2 mL) was slowly added to a cooled (0 °C) solution of the appropriate nitrobenzenesulfonyl (nosyl) chloride 2 (5.0 g, 22.6 mmol) in THF (50 mL), and the mixture was stirred at r.t. for 3 h. The mixture was then concentrated in vacuo. The residue was dissolved in Et₂O (200 mL), washed with sat. aq NaHCO₃ (200 mL) and brine (200 mL), dried (Na₂SO₄), and concentrated in vacuo. The residue was dissolved in 1:1:1 Et₂O–CH₂Cl₂–EtOAc (30 mL) at –40 °C, and hexane (250 mL) was added. The precipitate was then collected by filtration. o-Nitrobenzenesulfonyl Azide (1a)Prepared from o-nitrobenzenesulfonyl chloride (2a; 5.0 g, 22.6 mmol) according to the general procedure as a white solid; yield: 4.92 g (96%); mp 73–74 °C; R_f = 0.25 (EtOAc–hexane, 1:5). ¹H NMR (500 MHz, CDCl₃): δ = 8.20 (dd, J = 7.8, 1.4 Hz, 1 H), 7.93 (dd, J = 7.9, 1.5 Hz, 1 H), 7.89 (td, J = 7.6, 1.5 Hz, 1 H), 7.84 (td, J = 7.6, 1.6 Hz, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 147.68, 135.76, 133.09, 132.50, 131.65, 125.35. HRMS (EI+): m/z [M⁺] calcd for C₆H₄N₄O₄S: 227.9953; found: 227.9956.
• 21 o-Nitrobenezenesulfonyl Hydrazide (2a′)An 80% solution of N₂H₄·H₂O (4.2 mL, 68.5 mmol) was added to a cooled (0 °C) solution of o-nitrobenzenesulfonyl chloride (2a; 3.0 g, 13.5 mmol) in THF (20 mL), and the mixture was stirred at r.t. for 1 h. The mixture then was concentrated in vacuo. The residue was dissolved in EtOAc (100 mL), washed with sat. aq NaHCO₃ (100 mL) and brine (100 mL), dried (Na₂SO₄), and concentrated in vacuo. The residue was dissolved in CH₂Cl₂ (5 mL) at –40 °C, and hexane (100 mL) was added. The precipitate was collected by filtration to give a white solid; yield: (2.37 g, 81%); mp 100–101 °C; R_f = 0.30 (MeOH–CH₂Cl₂, 1:15).¹H NMR (500 MHz, CD₃CN): δ = 8.07 (ddd, J = 7.2, 2.0, 1.2 Hz, 1 H), 7.87 (ddd, J = 7.5, 2.3, 1.2 Hz, 1 H), 7.85 (td, J = 7.6, 1.5 Hz, 1 H), 7.82 (td, J = 7.5, 1.8 Hz, 1 H), 6.92 (br s, 1 H), 4.00 (br s, 2 H). ¹³C NMR (125 MHz, CD₃CN): δ = 149.43, 135.46, 133.41, 133.14, 130.86, 125.81. HRMS (FAB+): m/z [M + H]⁺ calcd for C₆H₈N₃O₄S: 218.0236; found: 218.0231.
• 22 γ-¹⁵N-Labeled o-Nitrobenezenesulfonyl Azide (γ-1a')1 N aq HCl (10 mL) was added to a solution of 2a′ (1.78 g, 8.22 mmol) in CH₂Cl₂ (40 mL), and the mixture was stirred at 0 °C for 5 min. A solution of Na¹⁵NO₂ (0.50 g, 7.14 mmol) in H₂O (10 mL) was then slowly added, and the resulting mixture was stirred at r.t. for a further 3 h. The mixture was then concentrated in vacuo. The residue was dissolved in Et₂O (150 mL), washed with sat. aq NaHCO₃ (150 mL) and brine (150 mL), dried (Na₂SO₄), and concentrated in vacuo. The residue was purified by flash chromatography [silica gel, EtOAc–hexane (1:10)] to give a white solid; yield: 1.52 g (81%); mp 73–74 °C; R_f = 0.25 (EtOAc–hexane, 1:5).¹H NMR (500 MHz, CDCl₃): δ = 8.20 (dd, J = 7.8, 1.4 Hz, 1 H), 7.92 (dd, J = 7.9, 1.8 Hz, 1 H), 7.90 (td, J = 7.5, 1.2 Hz, 1 H), 7.84 (ddd, J = 7.8, 7.0, 2.0 Hz, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 147.62, 135.79, 133.11, 132.41, 131.62, 125.34. ¹⁵N NMR (50 MHz, CDCl₃): δ = 245.31. HRMS (EI+): m/z [M⁺] calcd for C₆H₄N₃ ¹⁵NO₄S: 228.9924; found: 228.9921.
• 23 See the Supporting Information for more information.
• 24 Computational Details^26,27 NBO analysis was performed on the structure optimized in the gas phase at the DFT level with the B3LYP functional and the 6–311++G(2d) basis set in Gaussian 16.
• 25a Kaljurand I, Kütt A, Sooväli L, Rodima T, Mäemets V, Leito I, Koppel IA. J. Org. Chem. 2005; 70: 1019
• 25b Tshepelevitsh S, Kütt A, Lõkov M, Kaljurand I, Saame J, Heering A, Plieger PG, Vianello R, Leito I. Eur. J. Org. Chem. 2019; 6735
• 25c Kütt A, Tshepelevitsh S, Saame J, Lõkov M, Kaljurand I, Selberg S, Leito I. Eur. J. Org. Chem. 2021; 1407
• 26a Lee C, Yang W, Parr RG. Phys. Rev. B 1988; 37: 785
• 26b Becke AD. J. Chem. Phys. 1993; 98: 5648
• 27 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich AV, Bloino J, Janesko BG, Gomperts R, Mennucci B, Hratchian HP, Ortiz JV, Izmaylov AF, Sonnenberg JL, Williams-Young D, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski VG, Gao J, Rega N, Zheng G, Liang W, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Throssell K, Montgomery JA. Jr, Peralta JE, Ogliaro F, Bearpark MJ, Heyd JJ, Brothers EN, Kudin KN, Staroverov VN, Keith TA, Kobayashi R, Normand J, Raghavachari K, Rendell AP, Burant JC, Iyengar SS, Tomasi J, Cossi M, Millam JM, Klene M, Adamo C, Cammi R, Ochterski JW, Martin RL, Morokuma K, Farkas O, Foresman JB, Fox DJ. Gaussian 16, Revision A.03 . Gaussian, Inc.; Wallingford, CT: 2016