Rapid in Situ Generation of Benzene Diazonium Ions under Basic Aqueous Conditions from Bench-Stable Triazabutadienes

Abstract

Aryl diazonium ions are useful across a range of chemical/biochemical areas. These species are generally made using strongly acidic conditions, which can be detrimental to acid-sensitive functional groups. The ability to generate benzene diazonium ions under basic aqueous conditions is reported herein along with newfound understanding on the aqueous reactivity of solubilized triazabutadienes whereby π-interactions appear to confer a large degree of stability.

Key words

diazonium ions - acids - cleavage - bioorganic chemistry - protecting groups

• References and Notes

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• 5 Triazabutadienes are a subclass of triazazenes sometimes referred to as π-conjugated triazenes, see: Patil S. Bugarin A. Eur. J. Org. Chem. 2016; 860

Consistent with our ongoing work in the area,^6b the acid sensitivity of alkyl triazabutadienes was recently reported, see:
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• 11 No degradation was noted after greater than 1 month at r.t.
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• 13 Experimental Procedure for the Synthesis of 4 3-[1-(4-Bromo-2,6-dimethylphenyl)-1H-imidazol-3-ium-3-yl]propane-1-sulfonate (S2b) To a solution of 4-bromo-2,6-dimethylaniline (4 g, 20 mmol) in MeOH (5 mL) in a round-bottom flask was added glyoxal (2.9 mL, 20 mmol, 40% solution in water) with stirring. After a few minutes, a yellow sticky solid formed to which NH₄Cl (2.14 g, 40 mmol) and formaldehyde (3.2 mL 37 wt% in water) were added. The resulting mixture was diluted with 40 mL MeOH. The mixture was then refluxed for 1 h before H₃PO₄ (2.8 mL, 85 wt% in water) was added dropwise. The reaction was allowed to stir at reflux overnight. The solvent was removed under vacuum, and the residue was poured into 30 g ice. The aqueous mixture was neutralized with 40% KOH to pH 9 and extracted with CH₂Cl₂. The organic layer was separated, dried over MgSO₄, and concentrated to give compound S1b as light brown solid (50%). ¹H NMR (400 MHz, DMSO-d ₆): δ = 7.69 (1 H, dd, J = 1.2, 1.0 Hz), 7.53–7.48 (2 H, m), 7.24 (1 H, t, J = 1.3 Hz), 7.14 (1 H, dd, J = 1.2, 1.0 Hz), 1.97 (6 H, t, J = 0.7 Hz). To a solution of S1b (2.5 g, 10.0 mmol) in toluene (100 mL) in a round-bottom flask was added 1,3-propane sultone (1.8 g, 14.9 mmol). The mixture was then brought to reflux overnight. After cooling the reaction to r.t., the resulting precipitate was filtered and washed with ether to give S2b as a white solid (54%). The product was used for the next step without further purification. ¹H NMR (400 MHz, DMSO-d ₆) δ = 9.41 (1 H, t, J = 1.6 Hz), 8.13 (1 H, dd, J = 2.0, 1.5 Hz), 7.95 (1 H, t, J = 1.8 Hz), 7.62 (2 H, t, J = 0.7), 4.44 (2 H, t, J = 7.0 Hz), 2.46 (2 H, t, J = 7.0 Hz), 2.22 (2 H, quint, J = 7.0 Hz), 2.08 (6 H, s). 3-{(E)-3-[4-bromo-2,6-dimethylphenyl]-2-[(E)-phenyltriaz-2-en-1-ylidene]-2,3-dihydro-1H-imidazol-1-yl}propane-1-sulfonate (4) To a solution of S2b (200. mg, 0.54 mmol) in THF (10 mL), was added phenyl azide (64 mg, 0.54 mmol) in a THF (0.5 mL). The mixture was stirred for 5 min in an ice bath at which time KOt-Bu (78 mg, 0.70 mmol) was added in one portion. The mixture was slowly allowed to warm up to r.t. and stirred overnight. The reaction mixture was filtered through a plug of Celite, and the solvent was removed under vacuum to give the product as yellow solid (53%). ¹H NMR (400 MHz, DMSO-d ₆): δ = 7.47 (2 H, s), 7.32 (1 H, d, J = 2.5 Hz), 7.09 (2 H, dd, J = 8.3, 7.2 Hz), 7.02–6.97 (1 H, m), 6.87 (1 H, d, J = 2.5 Hz), 6.51–6.38 (2 H, m), 4.06 (2 H, t, J = 7.1 Hz), 2.50–2.47 (2 H, m), 2.07–2.05 (2 H, m), 1.97 (6 H, s). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 152.1, 151.1, 138.2, 137.5, 131.3, 128.7, 125.5, 121.3, 120.8, 118.0, 116.8, 48.5, 45.0, 25.7, 17.7
• 14 This constitutes a change in sigma value of roughly 0.5 as compared with the methyl group.
• 15 Guzman LE. Kimani FW. Jewett JC. ChemBioChem 2016; 17: 2220