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Tandem synthesis of 4-(6-Phenanthridinyl)morpholine through the Elimination of N2 and CO from Substituted Benzotriazole; 4-(6-Phenanthridinyl)morpholine

SyntheticPage 938
Submitted Oct 14, 2020, published Nov 09, 2020
Satyanarayana Battula (satyamssd@gmail.com)
A contribution from Satyam's Group


			Reaction Scheme: Tandem synthesis of 4-(6-Phenanthridinyl)morpholine through the Elimination of N<sub>2</sub> and CO from Substituted Benzotriazole

Chemicals Used

1. Phenylglyoxal hydrate (Sigma-Aldrich) 97%, 142433

2. Morpholine (Sigma-Aldrich) 99%, 134236

3. Benzotriazole (Sigma-Aldrich) 99%, B11400

4. Copper bromide (Sigma-Aldrich) 99%, 221775

5. Toluene (Rankem), directly used without drying

6. Ethyl acetate (SD Fine Chemicals Ltd), directly used without drying

7. Hexane (SD Fine Chemicals Ltd), directly used without drying

Procedure

A round-bottom flask fitted with a reflux condenser was charged with a stir bar and it was being added 0.460 mmol of phenylglyoxal (70 mg), 0.506 mmol of morpholine (44 µL), 0.552 mmol of benzotriazole (66 mg) and10 mol % of CuBr2 (10 mg) in 2 ml of toluene.  The reaction mixture was allowed to stir at 80 oC for 3-5 h. Completion of the reaction was studied by TLC technique [solvent system EtOAc and hexane  (1:9), and Rf of the product spot is 0.7) and after its completion, the reaction mixture was allowed to cool to room temperature. The crude reaction mass was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure and the product was purified by column chromatography using silica gel (100-200 #). Column was eluted with ethyl acetate and hexane (2:98) to obtain desired 4-(6-phenanthridinyl)morpholine in 71% (86 mg) yield.

Author's Comments

  • No need of any special conditions required for this reaction, reactions should perform in fume hood.
  • Phenylglyoxal reacts with morpholine to produce 2-oxoiminium ion and that react with benzotriazole to produce 4-(6-phenanthridinyl)morpholine through 2-oxo group promoted eliminations of nitrogen and carbon monoxide.
  • This reaction is driven by a novel in-situ generated functional group “CO-CH(N1N2)” driven ring opening/ N2 elimination leads to generate the final product 4-(6-phenanthridinyl)morpholine in good yields.
  • This reaction offers a first general and easier protocol for the synthesis of 4-(6-phenanthridinyl)morpholine.

Data

1H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 8.2 Hz, 1H), 8.44 (d, J = 8.0 Hz, 1H), 8.21 (d, J = 8.0 Hz, 1H), 7.94 (d, J = 8.1 Hz, 1H), 7.78 (t, J = 7.5 Hz, 1H), 7.63 (q, J = 6.9 Hz, 2H), 7.51 (t, J = 7.5 Hz, 1H), 4.01 (t, J = 4.2 Hz, 4H), 3.51 (t, J = 4.2 Hz, 4H);

13C NMR (126 MHz, CDCl3) δ 159.90, 143.71, 135.02, 130.22, 128.75, 128.59, 126.74, 126.37, 124.92, 122.78, 122.67, 121.88, 121.29, 67.10, 51.72;

IR (CHCl3, cm-1) ν 2933, 2922, 1532, 1442, 1384, 772;

ESI-MS: 265.1  m/z (M + H)+; HRMS: 265.1332 m/z calcd for C17H16N2O + H+ (265.1341).


Lead Reference

Battula, S.; Kumar, A.; Gupta, A. P.; Ahmed, Q. N. 2- Oxo Driven N2 Elimination Induced Decarbonylative Cyclization reaction in Benzotriazoles to 6-Aminophenanthridines. Org. Lett. 2015, 17, 5562-5565. (https://doi.org/10.1021/acs.orglett.5b02699)

Other References

Supplementary Information

NMR spectrum (Data File.docx)

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Get structure file (.cdx, .sk2, .mol)

Keywords: 6-aminophenanthridines, antiprion, benzotriazoles, heterocyclic compounds, N2 extrusion, transition metal catalysed

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