Selective Synthesis of N-H and N-Aryl Benzotriazoles by the [3 + 2] Annulation of Sodium Azide with Arynes

Abstract

The synthetic utility of NaN3 as the azide component in the [3 + 2] annulation with arynes generated from 2-(trimethylsilyl)­aryltriflates resulting in the transition-metal-free synthesis of N-H and N-aryl benzotriazoles has been demonstrated. Using CsF as the fluoride source in CH3CN, the N-H benzotriazoles are formed in high selectivity instead of the expected azidobenzene. Interestingly, N-aryl benzotriazoles are formed using KF and THF as solvent in an open-flask reaction. Moreover, a method for the N1-arylation of benzotriazole is also presented.

Poly(ethylene glycol) Dimethyl Ethers (PEGDME): Efficient and Recyclable Solvents for Aryne-Involved Reactions

“…A coupling reaction of enamide 5 with aryne under additive-free condition gave product 6 in only 33% yield (Condition C, Scheme 2a), but interestingly, when we used PEGDME as a solvent the reaction produced compound 6 in improved yield (45% yield, Condition B, Scheme 2a), which is almost similar to the condition with 18-Crown-6 as an additive/PTC in THF (50% Condition A, Scheme 2a). 12 The cycloaddition reaction of aryne with sodium azide 13 in PEGDME provided N-phenyl benzotriazole (8) as a major product (60%, Condition E, Scheme 2b) and benzotriazole (7) as a minor product (10%) where the reported protocol gave the benzotriazole (7) as the major product (62%, Condition D, Scheme 2b) and a low yield was obtained in the absence of additive in ACN (20%, Condition F, Scheme 2b). Since the solubility of cesium fluoride is high compared to potassium fluoride in conventional solvents, we examined the reported aryne reactions using potassium fluoride.…”

“…Yields refer to purified, dried, and spectroscopically pure compounds. 1 H and 13 C NMR spectra were recorded in CDCl3 or DMSO-d6 using 400 or 500 MHz ( 1 H) and 101 or 126 MHz ( 13 C). Chemical shifts (δ-values) are reported in ppm, spectra were calibrated related to solvent's residual proton chemical shifts (CDCl3, δ = 7.26, or DMSO-d6, δ = 2.5 ppm) and solvent's residual carbon chemical shifts (CDCl3, δ = 77.16, or DMSO-d6, δ = 39.52 ppm), multiplicity is reported as follows: s = singlet, d = doublet, dd = doublet of doublet, t = triplet, td = doublet of triplet, ddd = doublet of doublet of doublet, m = multiplet or unresolved, and coupling constant J in Hz.…”

“…15 To further explore the reactivity of benzyne 2 in PEGD-ME (average molecular weight 240) in multi-component reactions, experiments were carried out using KF as the fluoride source. Thus, the reaction of 4-nitrobenzaldehyde (13) with potassium iodide under the optimized conditions (PEGDME and KF) gave 2-iodobenzyl alcohol analogue 15 in 62% yield (Scheme 3a). 16 A three-component aminoselenation of aryne 2 using N,N-dimethylaniline (16) and phenyl selenium bromide (17) gave 2-aminophenyl selenium ana-…”

“…1 H NMR (400 MHz, CDCl 3 ):  = 8.21-8.16 (m, 3 H), 7.93 (s, 1 H), 7.87 (d, J = 8.0 Hz, 1 H), 7.68-7.64 (m, 1 H), 7.58-7.48 (m, 3 H), 7.43-7.38 (m, 1 H), 3.41 (q, J = 7.5 Hz, 2 H), 1.54 (t, J = 7.6 Hz, 3 H). 13 General procedure A: A mixture of sodium azide (130 mg, 2.0 mmol, 4.0 equiv), 2 (150 mg, 0.50 mmol, 1.0 equiv), 18-crown-6 (660 mg, 2.5 mmol, 5.0 equiv) and CsF (377 mg, 2.5 mmol, 5.0 equiv) in CH 3 CN (3 mL) was stirred at 70 °C for 12 h. Product 7 was isolated as a colorless solid (37 mg, 62%).…”

Leaving Groups in Metal‐Free Arylations: Make Your Choice!

“…[68] A remarkable exception is the ortho-(trimethylsilyl)aryl triflates discovered in early '80s by Kobayashi, [69] that act as the precursor of arynes under activation by a fluoride anion source. [70] The so-generated intermediates have a key-role in wide range of synthetic protocols, including, among the others, the preparation of 3-(2-Hydroxyaryl)quinolines and 4-(2-Hydroxyaryl)pyridines, quinolines acridines (by coupling with the corresponding heterocycle N-Oxides), [71] benzotriazole (in the presence of sodium azide) [72] and sulfones (by using sulfinate salts as the trapping agent). [73] The reactivity of 2-(trimethylsilyl)aryl triflates is on the basis of a thioamination protocol that gives access to orthosulfanylanilines under metal-free conditions.…”