Catalytic Preparation of 1-Aryl-Substituted 1,2,4-Triazolium Salts.

1,4-Diaryl- and 1-aryl-4-alkyl-substituted 1,2,4-triazolium salts are convenient air-stable precursors to carbenes used both as organocatalysts or as ligands for transition metal complexes. Traditionally, they are prepared via a multistep synthetic pathway with the low-yielding formation of the triazolium ring occurring in the last step. We have developed an alternative two-step synthesis involving the conversion of a primary amine or aniline derivative to the corresponding 4-substituted triazole followed by a copper-catalyzed arylation with diaryliodonium salts. This transition metal-catalyzed arylation can be carried out under mild conditions in acetonitrile and is tolerant toward both water and oxygen. Additionally, the high functional group tolerance of the protocol described here gives easy access to triazolium salts containing heterocyclic substituents or sulfides.

Introduction

Mostly known as convenient, air-stable precursors to N-heterocyclic carbenes (NHCs) used in organocatalytic transformations,[1−7] 1,2,4-triazolium salts also form upon deprotonation of NHC ligands for transition metal catalysts.[7−12] Beyond the field of catalysis, these 1,2,4-triazole-based ligands form phosphorescent cyclometalated complexes with the substituents on the carbene ligand being key to their tunable emission wavelengths,[13−15] while other late transition metal complexes containing 1,2,4-triazole ligands have shown promising in vitro anticancer activity in studies involving breast, colon, lung, skin, liver, and cervical cancer as well as leukemia.[16−20]N-Aryl-substituted 1,2,4-triazoles are also frequent building blocks in organic compounds with biological activity.[21−23] Although less common than imidazolium or 1,2,3-triazolium salts, 1,2,4-triazolium salts have been successfully used as ionic liquids for dissolving cellulose.[24]

Traditionally, 1-aryl-substituted 1,2,4-triazolium salts are prepared in three steps via a condensation reaction between an oxadiazolium intermediate derived from an aryl hydrazine and a primary amine (Scheme a).[25−28] There are several disadvantages of this synthetic route: First, the oxadiazolium intermediates are not only highly water-sensitive and decompose within minutes upon exposure to air but their formation also requires perchloric acid, thus raising safety concerns regarding the scaling up of the procedure. Second, many aryl hydrazines are either not readily available or very expensive. Third, while phenyl hydrazine proved to be unproblematic and yielded the desired intermediates nearly quantitatively, we were never able to isolate more than 8% of the 3-mesityl-1,3,4-oxadiazolium intermediate derived from the electron-rich mesityl hydrazine. We therefore decided to investigate alternative routes to 1,4-diaryl- and 1-aryl-4-alkyl-substituted 1,2,4-triazolium salts. Scheme b shows our approach in which the primary amine RNH2 is first converted to the 4-R-4H-1,2,4-triazole, followed by a copper-catalyzed N-arylation using diaryliodonium salts.

Scheme 1

Preparation of 1-Aryl-Substituted 4H-1,2,4-Triazolium Salts from Primary Amines

The use of diaryliodonium salts is well established for the arylation of a wide range of oxygen and nitrogen nucleophiles both with and without a copper catalyst.[29−31] Chen and co-workers have described a copper-free route to N-aryl pyridinium species from diaryliodonium salts and pyridinium N-oxides or sulfonamidates via a radical rearrangement;[32,33] however, the N-arylation of pyridines themselves requires a copper catalyst.[34,35] Most similar to this work describing the 1-arylation of triazoles is a recent report by Kumar et al. investigating a copper-catalyzed N-arylation of [1,2,4]triazolo[4,3-a]pyridines leading to fused triazolium salts.[36] To our knowledge, there have been no examples described in the literature for the copper-catalyzed 1-arylation of monocyclic triazoles with diaryliodonium salts; however, the preparation of 4-aryltriazolium or 3-arylimidazolium salts via similar methods has been reported before.[37−47]

Results and Discussion

We were aiming to find the mildest conditions to carry out the copper-catalyzed quaternization within short reaction times. To optimize the copper-catalyzed 1-arylation of 4-R-4H-1,2,4-triazoles, we initially carried out a series of reactions on a 0.5 mmol scale with 4-benzyl-4H-1,2,4-triazole (1a) and diphenyliodonium tetrafluoroborate, which we monitored by LC-MS (Table ). We found that at 100 °C, >95% conversion was achieved in the presence of all copper(I) and copper(II) catalysts except CuI after 4 h in DMF and acetonitrile, while reactions in water required prolonged reaction times (entries 1–13). When lowering the reaction temperature to 80 °C in acetonitrile, copper(I) proved to be superior to copper(II): After 4 h, 100% conversion was observed with CuOAc but only 87 and 88% were found with anhydrous Cu(OAc)2 and Cu(OAc)2·H2O, respectively (entries 14–16). Without the addition of a copper catalyst, the conversion dropped to 17% after 4 h of reaction time (entry 17). When shortening the reaction time to 1 h, the presence of CuOAc led to 97% conversion, while anhydrous Cu(OAc)2 and Cu(OAc)2·H2O showed significantly lower conversions (entries 18–20), thus being consistent with CuOAc being the most efficient catalyst. Since no unwanted side reactions were observed under these conditions, we decided to carry out the copper-catalyzed 1-arylation of triazoles with CuOAc in acetonitrile at 80 °C.

Table 1

Optimization of Reaction Conditionsa

entry	Cu catalyst	catalyst loading	Ph2l(BF4) (equiv)b	solvent	temperature	time	conversionc
1	Cu(OAc)2·H2O	5 mol%	1.5	DMF	100 °C	4 h	>95%
2	Cu(OAc)2	5 mol%	1.5	DMF	100 °C	4 h	>95%
3	Cu(OAc)	5 mol%	1.5	DMF	100 °C	4 h	>95%
4d	Cu(OAc)2	5 mol%	1.5	H2O	100 °C	4 h	>80%
5d	Cu(OAc)	5 mol%	1.5	H2O	100 °C	4 h	>80%
6	Cu(OAc)2·H2O	5 mol%	1.5	MeCN	100 °C	4 h	>95%
7	Cu(OAc)2	5 mol%	1.5	MeCN	100 °C	4 h	>95%
8	Cu(OAc)	5 mol%	1.5	MeCN	100 °C	4 h	>95%
9	Cu(OTf)·0.5 toluene	5 mol%	1.5	MeCN	100 °C	4 h	>95%
10	Cu(TC)	5 mol%	1.5	MeCN	100 °C	4 h	>95%
11	Cu(OTf)2	5 mol%	1.5	MeCN	100 °C	4 h	>95%
12	Cu(acac)2	5 mol%	1.5	MeCN	100 °C	4 h	>95%
13	Cul	5 mol%	1.5	MeCN	100 °C	4 h	<30%
14	Cu(OAc)2·H2O	5 mol%	1.5	MeCN	100 °C	4 h	88%
15	Cu(OAc)2	5 mol%	1.5	MeCN	100 °C	4 h	87%
16	Cu(OAc)	5 mol%	1.5	MeCN	100 °C	4 h	100%
17	none		1.5	MeCN	100 °C	4 h	17%
18	Cu(OAc)2·H2O	5 mol%	1.5	MeCN	100 °C	1 h	80%
19	Cu(OAc)2	5 mol%	1.5	MeCN	100 °C	1 h	79%
20	Cu(OAc)	5 mol%	1.5	MeCN	100 °C	1 h	97%

Reaction conditions: triazole 1a (0.5 mmol), Ph2IBF4, Cu catalyst (relative to 1a), solvent (2 mL), and reaction time.

Relative to 1a.

Conversion based on LC-MS analysis.

After 18 h, >95% conversion.

To explore the scope of the copper-catalyzed N-arylation, we prepared a variety of 4-R-4H-1,2,4-triazoles 1a–1m from the corresponding primary amines R-NH2 as described in Scheme b.[48−54]Table summarizes the results of the 1-arylation of 1a–1m with diphenyliodonium tetrafluoroborate using our previously optimized conditions. Based on NMR studies, 100% conversion was observed with all 4-R-4H-1,2,4-triazoles 1a–1m, and the corresponding 1-phenyl-4-R-4H-1,2,4-triazolium salts 2a–2m were obtained as sole products in good to excellent yields (Figures S002–S015). While this was not surprising with simple alkyl (2a–2c), aryl (2d and2e), or haloaryl substituents (2g–2k), the copper-catalyzed arylation of 1f gave 2f cleanly without any arylation of the para-methoxy-substituted sulfide. Likewise, although 1l and 1m contain several heteroaryl nitrogen atoms that could be quaternized, 2l and 2m form preferentially and none of the other possible arylation products were observed under the chosen reaction conditions despite the presence of an excess of diaryliodonium tetrafluoroborate. The isolated yields were generally within 5–10% of the NMR yields. However, significantly lower isolated yields were obtained with the heteroaryl-substituted triazolium salts 2l, which was strongly retained on silica, and 2m, which decomposed on silica and had to be purified by recrystallization.

Table 2

Scope of 1,2,4-Triazolesa

Reaction conditions: triazoles 1a–1m (1.0 mmol), Ph2IBF4 (1.5 mmol), CuOAc (0.05 mmol, 5 mol%), MeCN (4 mL), 80 °C, and 4 h.

Conversion based on NMR analysis.

NMR yield as determined by 1H NMR analysis relative to mesitylene as the internal standard.

Isolated yield.

Since the 1-aryl substituent governs the electronic properties of 1,2,4-triazolium salts used for organocatalytic transformations, a late stage introduction of the aryl group appears to be of general interest to the organic community. We found that with our N-arylation method, we were able to introduce a variety of aryl groups in the last synthetic step, using triazole 1d to investigate the scope of diaryliodonium salts in the copper-catalyzed quaternization of triazoles (Table ). We observed that both the use of diaryliodonium tetrafluoroborates and triflates resulted in complete conversion to the corresponding 1-aryl-4-phenyltriazolium salts (2d–9d) within 4 h of reaction time. Unhindered electron-rich (e.g., 6d) and electron-poor (e.g., 7d) aryl groups were introduced with high yields, whereas a decreased isolated yield was observed for ortho-substituted aryl groups (3d–5d). Although LC-MS indicated complete conversion, we were unable to isolate 9d.

Table 3

Scope of Diaryliodonium Saltsa

Reaction conditions: triazole 1d (1.0 mmol), Ar2IBF4 or Ar2IOTf (1.5 mmol), CuOAc (0.05 mmol, 5 mol%), MeCN (4 mL), 80 °C, and 4 h.

Conversion based on NMR analysis.

NMR yield as determined by 1H NMR analysis relative to mesitylene as the internal standard.

Isolated yield.

Conversion determined by LC-MS.

In the hope to find a way to isolate 9d, we decided to investigate the use of unsymmetrical diaryliodonium salts for the quaternization of triazole 1d (Scheme ).[30] Unfortunately, with mesityl(perfluorophenyl)iodonium triflate, only traces of the desired compound 9d were detected, and 5% of the side product 4d was isolated. The remaining components of the mixture consisted of unreacted starting materials including the unreacted mesityl(perfluorophenyl)iodonium triflate. However, when mesityl(phenyl)iodonium triflate was used instead for the N-arylation, the more electron-deficient phenyl group was, as expected, transferred preferentially giving 2d with 95% selectivity.[29] Efficient separation of 2d from the side product 4d was only possible on a small scale by column chromatography, thus making the use of symmetrical diaryliodonium salts more desirable for the N-arylation of triazoles (Table ).

Scheme 2

N-Arylation with Unsymmetrical Diaryliodonium Triflates

Due to their very low yields via the traditional route (Scheme a), we were particularly interested in applying our N-arylation method to the synthesis of 1-mesityl-substituted 1,2,4-triazolium salts 4a–4l (Table ). Although complete conversion was observed for all reactions, the isolated yields were generally lower than for the corresponding phenyl derivatives (Table ) due to more challenging separation of the desired product from IMes2OTf by column chromatography. Indeed, we did observe increased yields upon scale-up of the catalytic reactions (e.g., with 4c) as this allowed us to purify the triazolium salts by recrystallization.

Table 4

Synthesis of 1-Mesityl Triazolium Saltsa

Reaction conditions: triazoles 1a–1l (1.0 mmol), Mes2IOTf (1.5 mmol), CuOAc (0.05 mmol, 5 mol%), MeCN (4 mL), 80 °C, and 4 h.

Conversion based on NMR analysis.

NMR yield as determined by 1H NMR analysis relative to mesitylene as the internal standard.

Isolated yield.

Isolated yield; 8 mmol scale.

The copper-catalyzed quaternization of 4-R-1,2,4-triazoles 1a–1m provides an efficient route for systematically varying not only electronic but also steric parameters of triazolium salts (Table ). Unsymmetrically substituted electron-rich carbene precursors (3j and 5b) as well as sterically hindered electron-poor 1,2,4-triazolium salts (7e and 8e) were readily prepared in high yields. The electron-rich pyrimidine derivative 6m was found to form cleanly, but its separation from the remaining diaryliodonium salt provided a challenge since 6m was observed to decompose on silica.

Table 5

Variation of Steric and Electronic Parametersa

Reaction conditions: triazoles 1a–1m (1.0 mmol), Ar2IBF4 or Ar2IOTf (1.5 mmol), CuOAc (0.05 mmol, 5 mol%), MeCN (4 mL), 80 °C, and 4 h.

Conversion based on NMR analysis.

NMR yield as determined by 1H NMR analysis relative to mesitylene as the internal standard.

Isolated yield.

Isolated yield; 3 mmol scale.

As demonstrated above, our optimized reaction conditions proved to be ideal from a synthetic perspective for achieving complete N-arylation of 4-R-1,2,4-tiazoles within short reaction times. Nevertheless, we were curious how specific reaction parameters such as temperature, catalyst loading, or stoichiometry of the diaryliodonium salt would impact the rate and completeness of the N-arylation. In particular, lowering the reaction temperature might allow the use of triazoles containing sensitive functional groups. Indeed, further investigation of the reaction temperature (Figure ) indicated that although the reaction rate decreases significantly below 60 °C, prolonged reaction times led to complete conversion.

Figure 1

Temperature dependence.

Similarly, lowering the catalyst loading from 5 to 1 mol% or 0.5 mol%, resulted in slower but complete product formation within 4 h with the chosen test substrates (Figure ). Accordingly, while quaternization was still observed without the addition of the copper catalyst at 80 °C, N-arylation occurred at significantly lower rates, and 82% conversion was obtained after 23 h.

Figure 2

Catalyst loading.

Since all reactions proceeded cleanly to the desired products, we rationalized that addition of stoichiometric quantities of diaryliodonium salt should lead to complete product formation. Indeed, when the loading of diaryliodonium salt was decreased to either 1.25 or 1.1 equivalents, the reaction still went to completion but required more time (Figure ). With 1.0 equivalents of diaryliodonium salt complete conversion was observed after 24 h.

Figure 3

Stoichiometry of diaryliodonium salt.

Although the reaction proceeds slowly without a copper catalyst (Figure ), we propose in analogy to the related literature a Cu(I)/Cu(III) mechanism to be operative in the presence of a copper salt.[29,36,55] This is supported by our own findings that copper(I) proved to be more efficient than the corresponding copper(II) salt in catalyzing the N-arylation.

Conclusions

In summary, we have demonstrated an efficient alternative route for the preparation of 1-aryl-substituted 4R-4H-1,2,4-triazolium salts from 4-R-4H-1,2,4-triazoles via a copper-catalyzed quaternization using diaryliodonium salts. Key features of this pathway are a uniformly applicable protocol, short reaction times, complete conversions, and clean product formation.

Experimental Section

General Information

Most reagents and solvents were obtained from commercial sources and used as supplied unless otherwise noted. Acetonitrile used for catalytic reactions was dried under an inert atmosphere over CaH2 and distilled prior to use. DMSO-d6 was dried over molecular sieves.

Analyses

1H NMR, 13C{1H} NMR spectra, and 19F{1H} NMR spectra were all recorded on a 400 MHz Bruker Avance III spectrometer with a 5 mm liquid-state Smart Probe. Chemical shifts (δH and δC) are expressed in parts per million (ppm) and reported relative to the resonance of the residual protons of the DMSO-d6 (δH = 2.50 ppm) or CDCl3 (δH = 7.26 ppm) or in 13C{1H} NMR spectra relative to the resonance of the deuterated solvent DMSO-d6 (δC = 39.52 ppm) or CDCl3 (δC = 77.16 ppm). Chemical shifts in 19F{1H} NMR spectra are reported relative to the internal standard fluorobenzene (δF = −113.15). Coupling constants (J) are given in Hz. All measurements were carried out at 298 K. Abbreviations used in the description of NMR data are as follows: s, singlet; d, doublet; t, triplet; q, quartet; sept, septet; and m, multiplet. High-resolution mass spectrometry (HRMS) data were obtained on an LTQ Orbitrap XL in FT Orbitrap mode at a resolution of 100,000.

General Procedure 1a for the Synthesis of Triazoles 1a–1m

The amine (1 equiv) and the dihydrochloride of N,N-dimethylformylamide azine (1.5 equiv) were ground together in a mortar until the mixture liquefied or became a homogeneous solid and then transferred to a round-bottom flask equipped with a stir bar. The flask was fitted with a reflux condenser, placed under an inert atmosphere, and heated in an oil bath to 150 °C for 16 h. After cooling to room temperature, the reaction mixture was basified with 1 M NaOH and then extracted with dichloromethane (3 × 100 mL). The combined organic phase was washed with water (2 × 50 mL), dried over MgSO4, filtered, and evaporated. The crude product was purified with column chromatography (5% methanol in dichloromethane) or by precipitation with hexanes or diethyl ether from a concentrated dichloromethane solution.

General Procedure 1b for the Synthesis of Triazoles 1a–1m

The amine (1 equiv), the dihydrochloride of N,N-dimethylformylamide azine (1.5 equiv), and para-toluenesulfonic acid (0.05 equiv) were ground together in a mortar until the mixture liquefied or became a homogeneous solid and then transferred to a round-bottom flask equipped with a stir bar. The reaction mixture was layered with xylenes, a reflux condenser was placed on the round-bottom flask, and the mixture was heated under argon in an oil bath to 150 °C for 16 h. After cooling to room temperature, the crude product was purified as described in procedure 1a.

4-Benzyl-4H-1,2,4-triazole (1a)

The title compound was prepared on a 50 mmol scale according to general procedure 1b. Purification by column chromatography (silica, 5% methanol in dichloromethane) yielded the product as a colorless powder in 42% yield (3.31 g, 20.8 mmol). The measured analytical data are in agreement with their literature values.[54]

4-Cyclohexyl-4H-1,2,4-triazole (1b)

The title compound was prepared on a 100 mmol scale according to general procedure 1b. Precipitation with hexanes from a concentrated dichloromethane solution gave the pure pale yellow product in 15% yield (2.19 g, 14.5 mmol). The measured analytical data are in agreement with their literature values.[51]

4-((3s,5s,7s)-Adamantan-1-yl)-4H-1,2,4-triazole (1c)

The title compound was prepared on a 100 mmol scale according to general procedure 1b. The crude product was dissolved in a minimal amount of 5% methanol in dichloromethane and precipitated with toluene, which gave the pure product as a colorless powder in 31% yield (6.38 g, 31.4 mmol). The measured analytical data are in agreement with their literature values.[52]

4-Phenyl-4H-1,2,4-triazole (1d)

The title compound was prepared according to general procedure 1b on a 50 mmol scale. The pure light brown product was obtained by precipitation with hexanes from a concentrated solution of dichloromethane. Yield: 73% (5.29 g, 36.5 mmol). The measured analytical data are in agreement with their literature values.[51,54]

4-(2,6-Diisopropylphenyl)-4H-1,2,4-triazole (1e)

The title compound was prepared according to general procedure 1a on a 50 mmol scale. Purification by column chromatography (silica, 5% methanol in dichloromethane) yielded the product as an off-white powder in 37% yield (4.20 g, 18.3 mmol). The measured analytical data are in agreement with their literature values.[48]

4-(2-((4-Methoxybenzyl)thio)phenyl)-4H-1,2,4-triazole (1f)

The title compound was prepared in 69% yield according to a literature procedure on a 100 mmol scale.[49] The measured analytical data are in agreement with their literature values.[49]

4-(2-Fluorophenyl)-4H-1,2,4-triazole (1g)

The title compound was prepared on a 25 mmol scale according to general procedure 1a. Purification by column chromatography (silica, 5% methanol in dichloromethane) yielded the product as an off-white powder in 48% yield (1.96 g, 12.0 mmol). 1H NMR (400 MHz, CDCl3, 298 K): δ 8.49 (s, 2H), 7.55–7.50 (m, 1H), 7.23–14 (m, 3H). 13C{1H} NMR (100 MHz, CDCl3, 298 K): δ 163.3 (d, JC–F = 250.7 Hz), 141.3, 135.1 (d, JC–F = 9.7 Hz), 132.0 (d, JC–F = 9.1 Hz), 117.9 (d, JC–F = 3.5 Hz), 116.2 (d, JC–F = 21.0 Hz), 110.1 (d, JC–F = 25.2 Hz). 19F{1H} NMR (376 MHz, CDCl3, 298 K, referenced to C6H5F): δ −110.21.

4-(3-Fluorophenyl)-4H-1,2,4-triazole (1h)

The title compound was prepared on a 25 mmol scale according to general procedure 1a. Purification by column chromatography (silica, 5% methanol in dichloromethane) yielded the product as a pale yellow powder in 26% yield (1.04 g, 6.38 mmol). 1H NMR (400 MHz, CDCl3, 298 K): δ 8.35 (d, JC–F = 1.5 Hz, 2H), 7.50–7.43 (m, 2H), 7.34–7.30 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3, 298 K): δ 154.3 (d, JC–F = 250.1 Hz), 142.3 (d, JC–F = 2.3 Hz), 130.8 (d, JC–F = 7.7 Hz), 125.2, 122.0 (d, JC–F = 12.3 Hz), 117.6 (d, JC–F = 19.3 Hz). 19F{1H} NMR (376 MHz, CDCl3, 298 K, referenced to C6H5F): δ −123.56.

4-(4-Fluorophenyl)-4H-1,2,4-triazole (1i)

The title compound was prepared on a 25 mmol scale according to general procedure 1a. Purification by column chromatography (silica, 5% methanol in dichloromethane) yielded the product as an off-white powder in 28% yield (1.16 g, 7.1 mmol). 1H NMR (400 MHz, CDCl3, 298 K): δ 8.45 (s, 2H), 7.43–7.38 (m, 2H), 7.28–7.22 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3, 298 K): δ 162.6 (d, JC–F = 250.1 Hz), 141.8, 130.0 (d, JC–F = 11.0 Hz), 132.4 (d, JC–F = 3.6 Hz), 124.5 (d, JC–F = 8.8 Hz), 117.4 (d, JC–F = 23.4 Hz). 19F{1H} NMR (376 MHz, CDCl3, 298 K, referenced to C6H5F): δ −110.10.

4-(2-Chlorophenyl)-4H-1,2,4-triazole (1j)

The title compound was prepared on a 25 mmol scale according to general procedure 1a. Purification by column chromatography (silica, 5% methanol in dichloromethane) yielded the product as an off-white powder in 51% yield (2.31 g, 12.9 mmol). 1H NMR (400 MHz, CDCl3, 298 K): δ 8.46 (s, 2H), 7.62–7.60 (m, 1H), 751–7.39 (m, 3H). 13C{1H} NMR (100 MHz, CDCl3, 298 K): δ 142.9, 131.5, 131.3, 131.2, 129.9, 128.5, 127.6.

4-(4-Chlorophenyl)-4H-1,2,4-triazole (1k)

The title compound was prepared on a 25 mmol scale according to general procedure 1a. Purification by column chromatography (silica, 5% methanol in dichloromethane) yielded the product as an off-white powder in 34% yield (1.51 g, 12.0 mmol). 1H NMR (400 MHz, CDCl3, 298 K): δ 8.47 (s, 2H), 7.51 (d, J = 8.8 Hz, 2H), 7.36 (d, J = 8.8 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3, 298 K): δ 141.5, 135.2, 132.4, 130.6, 123.7.

2-(4H-1,2,4-Triazol-4-yl)pyridine (1l)

The title compound was prepared on a 50 mmol scale according to general procedure 1a. Purification by column chromatography (silica, 5% methanol in dichloromethane) yielded the product as a pale yellow powder in 30% yield (2.22 g, 15.2 mmol). The measured analytical data are in agreement with their literature values.[53,54]

2-(4H-1,2,4-Triazol-4-yl)pyrimidine (1m)

The title compound was prepared on a 100 mmol scale according to general procedure 1b. Purification by column chromatography (silica, 5% methanol in dichloromethane) yielded the product as a pale yellow powder in 7.4% yield (1.09 g, 7.4 mmol). The measured analytical data are in agreement with their literature values.[56]

General Procedure 2a for the Catalytic Arylation of Triazoles 1a–1m

A 10 mL Schlenk flask equipped with a stir bar was loaded with the triazole (1 mmol, 1.0 equiv), diaryliodonium salt (1.5 mmol, 1.5 equiv), and copper(I) acetate (0.05 mmol, 5 mol%), sealed with a PTFE screwcap, and filled with argon. Dry acetonitrile (4 mL) was added under a stream of argon, and the flask was resealed, then placed into an oil bath, and stirred for 4 h at 80 °C. After the reaction mixture was cooled to room temperature, the solvent was evaporated. NMR yields and conversion were determined by addition of mesitylene (1 mmol, 1 equiv) in DMSO-d6 to the crude reaction mixture. The pure triazolium salts were obtained either by recrystallization or column chromatography (dichloromethane/acetone, 4:1) as described below.

General Procedure 2b for the Catalytic Arylation of Triazoles 1a–1m

A 5 mL microwave tube equipped with a stir bar was loaded inside a glovebox with the triazole (0.5 mmol, 1.0 equiv) and the diaryliodonium salt (0.75 mmol, 1.5 equiv). After sealing the microwave tube and removing it from the glovebox, the catalyst (copper(I) acetate (0.025 mmol, 0.05 equiv, 5 mol%) in 2 mL of acetonitrile) was added via syringe to the reaction mixture. The reaction mixture was then stirred for 4 h in an oil bath at 80 °C, cooled to room temperature, and concentrated. NMR yields and conversion were determined by addition of mesitylene (0.5 mmol, 1 equiv) in DMSO-d6 to the crude reaction mixture. The pure triazolium salts were obtained either by recrystallization or column chromatography (dichloromethane/acetone, 4:1) as described below.

4-Benzyl-1-phenyl-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([2a]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.28) yielded the product as an off-white powder in >99% yield (161 mg, 0.498 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 10.98 (s, 1H), 9.52 (s, 1H), 7.92 (d, J = 7.7 Hz, 2H), 7.72–7.68 (m, 2H), 7.64 (t, J = 7.3 Hz, 1H), 7.56 (d, J = 7.6 Hz, 2H), 7.50–7.44 (m, 3H), 5.59 (s, 2H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 145.0, 141.8, 135.0, 133.2, 130.6, 130.2, 129.1, 129.0, 128.8, 120.8, 51.0. HRMS (ESI) calcd for [C15H14N3]+, 236.1182; observed, 236.1171.

4-Cyclohexyl-1-phenyl-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([2b]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.33) yielded the product as an off-white powder in 90% yield (141 mg, 0.449 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 10.86 (s, 1H), 9.54 (s, 1H), 7.95 (d, J = 7.7 Hz, 2H), 7.73–7.69 (m, 2H), 7.63 (t, J = 7.3 Hz, 1H), 4.45 (tt, J = 11.7, 4.0 Hz, 1H), 2.28–2.24 (m, 2H), 1.91–1.69 (m, 5H), 1.49–1.38 (m, 2H), 1.25–1.19 (m, 1H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 143.9, 140.5, 135.1, 130.5, 130.1, 120.7, 58.4, 32.0, 24.4, 24.2. HRMS (ESI) calcd for [C14H18N3]+, 228.1495; observed, 228.1487.

4-((3s,5s,7s)-Adamantan-1-yl)-1-phenyl-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([2c]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.36) yielded the product as a white powder in 70% yield (128 mg, 0.348 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 10.83 (s, 1H), 9.71 (s, 1H), 7.99 (d, J = 7.7 Hz, 2H), 7.73–7.69 (m, 2H), 7.63 (t, J = 7.3 Hz, 1H), 2.26 (bs, 9H), 7.99 (d, J = 7.7 Hz, 2H), 7.99 (d, J = 7.7 Hz, 2H), 1.78 (d, J = 12.4 Hz, 3H), 1.72 (d, J = 12.4 Hz, 3H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 142.6, 139.7, 135.2, 130.4, 130.1, 120.8, 60.6, 41.4, 34.9, 28.82. HRMS (ESI) calcd for [C18H22N3]+, 280.1808; observed, 280.1797.

1,4-Diphenyl-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([2d]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.22) yielded the product as an off-white powder in 96% yield (148 mg, 0.479 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.43 (s, 1H), 10.01 (s, 1H), 8.04 (d, J = 7.7 Hz, 2H), 7.94 (d, J = 7.7 Hz, 2H), 7.79–7.75 (m, 4H), 7.72–7.67 (m, 2H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 143.3, 140.5, 134.9, 132.1, 130.8, 130.3, 122.6, 120.8. HRMS (ESI) calcd for [C14H12N3]+, 222.1026; observed, 222.1019.

1,4-Diphenyl-4H-1,2,4-triazol-1-ium Trifluoromethanesulfonate ([2d]OTf)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.17) yielded the product as a white powder in 95% yield (176 mg, 0.473 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.43 (s, 1H), 10.01 (s, 1H), 8.04 (d, J = 7.7 Hz, 2H), 7.94 (d, J = 7.7 Hz, 2H), 7.79–7.75 (m, 4H), 7.72–7.67 (m, 2H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 143.3, 140.5, 134.9, 132.1, 130.8, 130.3, 122.6, 120.7. HRMS (ESI) calcd for [C14H12N3]+, 222.1026; observed, 222.1022.

4-(2,6-Diisopropylphenyl)-1-phenyl-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([2e]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.56) yielded the product as an off-white powder in 96% yield (189 mg, 0.480 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.38 (s, 1H), 9.93 (s, 1H), 8.05 (d, J = 7.7 Hz, 2H), 7.78–7.67 (m, 4H), 7.54 (d, J = 7.7 Hz, 2H), 2.57 (sept, J = 6.7 Hz,12H’), 1.19 (d, J = 6.7 Hz, 6H’), 1.14 (d, J = 6.7 Hz, 6H’). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 146.0, 145.5, 142.1, 135.1, 132.4, 130.8, 130.0, 127.2, 124.8, 120.9, 27.7, 24.2, 23.5. HRMS (ESI) calcd for [C20H24N3]+, 306.1965; observed, 306.1958.

1-Phenyl-4-(2-((4-methoxybenzyl)thio)phenyl)-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([2f]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.35) yielded the product as an off-white powder in 79% yield (181 mg, 0.394 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.13 (s, 1H), 9.73 (s, 1H), 7.97 (d, J = 7.7 Hz, 2H), 7.89 (dd, J = 7.9, 1.4 Hz, 1H), 7.79–7.64 (m, 6H), 7.06 (d, J = 8.6 Hz, 2H), 6.76 (d, J = 8.6 Hz, 2H), 4.15 (s, 2H’), 3.64 (s,3H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 158.5, 145.5, 141.8, 134.7, 133.8, 132.2, 132.1, 132.0, 130.9, 130.3, 129.9, 128.9, 128.3, 127.2, 120.6, 113.9, 54.9, 38.4. HRMS (ESI) calcd for [C22H20N3OS]+, 374.1322; observed, 274.1305.

4-(2-Fluorophenyl)-1-phenyl-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([2g]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.17) yielded the product as an off-white powder in 95% yield (155 mg, 0473 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.47 (s, 1H), 10.03 (s, 1H), 8.03 (d, J = 7.7 Hz, 2H), 7.97–7.93 (m, 1H), 7.87–7.81 (m, 2H), 7.79–7.75 (m, 2H), 7.69 (t, J = 7.3 Hz, 1H), 7.62–7.57 (m, 1H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 162.2 (d, JC–F = 245.1 Hz), 143.3, 140.7, 134.8, 133.2 (d, JC–F = 11.0 Hz), 132.4 (d, JC–F = 8.8 Hz), 130.9, 130.4, 120.7, 118.7 (d, JC–F = 3.3 Hz), 117.7 (d, JC–F = 20.7 Hz), 110.4 (d, JC–F = 27.1 Hz). 19F{1H} NMR (376 MHz, DMSO-d6, 298 K, referenced to C6H5F): δ −109.97, −148.42. HRMS (ESI) calcd for [C14H11FN3]+, 240.0932; observed, 204.0922.

4-(3-Fluorophenyl)-1-phenyl-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([2h]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.17) yielded the product as a pale yellow powder in 96% yield (158 mg, 0.482 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.42 (s, 1H), 9.93 (d, J = 1.7 Hz, 1H), 8.03 (d, J = 7.7 Hz, 2H), 7.96 (dt, J = 7.8, 1.6 Hz, 1H), 7.82–7.67 (m, 5H), 7.61 (dt, J = 7.5, 1.6 Hz, 1H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 154.3 (d, JC–F = 252.7 Hz), 144.6 (d, JC–F = 3.8 Hz), 142.0, 134.8, 133.3 (d, JC–F = 8.0 Hz), 130.9, 130.3, 126.7, 126.0 (d, JC–F = 4.0 Hz), 121.0, 120.0 (d, JC–F = 11.3 Hz), 117.5 (d, JC–F = 18.4 Hz). 19F{1H} NMR (376 MHz, DMSO-d6, 298 K, referenced to C6H5F): δ −123.16, −148.41. HRMS (ESI) calcd for [C14H11FN3]+, 240.0932; observed, 240.0921.

4-(4-Fluorophenyl)-1-phenyl-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([2i]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.19) yielded the product as an off-white powder in 94% yield (154 mg, 0.470 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.42 (s, 1H), 9.96 (s, 1H), 8.04–7.98 (m, 4H), 7.78–7.75 (m, 2H), 7.71–7.64 (m, 3H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 162.9 (d, JC–F = 249.9 Hz), 143.5, 140.7, 134.9, 130.8, 130.4, 128.5 (d, JC–F = 2.9 Hz), 125.4 (d, JC–F = 9.6 Hz), 120.7, 117.4 (d, JC–F = 23.6 Hz). 19F{1H} NMR (376 MHz, DMSO-d6, 298 K, referenced to C6H5F): δ −109.92, −148.41. HRMS (ESI) calcd for [C14H11FN3]+, 240.0932; observed, 240.0921.

4-(2-Chlorophenyl)-1-phenyl-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([2j]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.19) yielded the product as an off-white powder in 95% yield (136 mg, 0.474 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.41 (s, 1H), 9.95 (s, 1H), 8.04 (d, J = 7.7 Hz, 2H), 7.97–7.92 (m, 2H), 7.81–7.68 (m, 5H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 153.9, 145.23, 142.4, 134.8, 133.3, 131.0, 130.3, 129.4, 129.0, 128.7, 128.5, 120.9. HRMS (ESI) calcd for [C14H11ClN3]+, 256.0636; observed, 256.0627.

4-(4-Chlorophenyl)-1-phenyl-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([2k]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.37) yielded the product as an off-white powder in 90% yield (155 mg, 0.491 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.45 (s, 1H), 10.00 (s, 1H), 8.03 (d, J = 7.7 Hz, 2H), 7.98 (d, J = 9.0 Hz, 2H), 7.89 (d, J = 9.0 Hz, 2H), 7.79–7.75 (m, 2H), 7.69 (t, J = 7.3 Hz, 1H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 143.3, 140.6, 135.4, 134.8, 131.0, 130.9, 130.4, 130.3, 124.5, 120.7. HRMS (ESI) calcd for [C14H11ClN3]+, 256.0636; observed, 256.0627.

1-Phenyl-4-(pyridin-2-yl)-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([2l]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.22) yielded the product as a white powder in 82% yield (127 mg, 0.410 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.68 (s, 1H), 10.24 (s, 1H), 8.77–8.75 (m, 1H), 8.37–8.32 (m, 1H), 8.15 (d, J = 8.1 Hz, 1H), 8.05 (d, J = 7.7 Hz, 2H), 7.78 (m, 3H), 7.69 (t, J = 7.3 Hz, 1H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 149.5, 144.7, 142.0, 140.9, 139.7, 134.9, 130.9, 130.28, 126.2, 120.9, 115.4. HRMS (ESI) calcd for [C13H11N4]+, 223.0978; observed, 223.0973.

1-Phenyl-4-(pyrimidin-2-yl)-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([2m]BF4)

The title compound was prepared according to general procedure 2b. After evaporation of the reaction solvent, the crude residue was washed with diethyl ether (5 mL), THF (3 × 5 mL), and acetone (3 × 2 mL). Recrystallization from methanol yielded the pure product as a pale yellow powder in 58% yield (89.9 mg, 0.288 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.83 (s, 1H), 10.33 (s, 1H), 9.19 (d, J = 4.9 Hz, 2H), 8.14 (d, J = 7.7 Hz, 2H), 7.91 (t, J = 4.9 Hz, 1H), 7.77–7.68 (m, 3H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 160.4, 151.0, 142.2, 140.1, 134.8, 131.0, 130.2, 123.4, 121.2. HRMS (ESI) calcd for [C12H10N5]+, 224.0931; observed, 224.0929.

4-Phenyl-1-(o-tolyl)-4H-1,2,4-triazol-1-ium Trifluoromethanesulfonate ([3d]OTf)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.17) yielded the product as an off-white powder in 81% yield (155 mg, 0.404 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.17 (s, 1H), 10.03 (s, 1H), 7.94 (d, J = 7.7 Hz, 2H), 7.79–7.53 (m, 7H), 2.40 (s, 3H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 143.0, 142.8, 134.1, 133.8, 132.1, 132.0, 131.6, 130.7, 130.2, 127.3, 126.3, 122.6, 17.3. HRMS (ESI) calcd for [C15H14N3]+, 236.1182; observed, 236.1174.

4-(2-Chlorophenyl)-1-(o-tolyl)-4H-1,2,4-triazol-1-ium Trifluoromethanesulfonate ([3j]OTf)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.24) yielded the product as a white powder in 67% yield (140 mg, 0.333 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.2 (s, 1H), 9.97 (s, 1H), 7.79 (dd, J = 7.5, 2.2 Hz, 1H), 7.94 (dd, J = 7.5, 2.0 Hz, 1H), 7.82–7.73 (m, 3H), 7.68–7.55 (m, 3H), 2.39 (s, 3H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 175.4, 164.8, 158.8, 156.3, 146.9, 144.2, 140.4, 131.5, 130.1, 127.0, 125.3, 122.9, 121.0, 38.3, 26.3. HRMS (ESI) calcd for [C15H13ClN3]+, 270.0793; observed, 270.0785.

4-Benzyl-1-mesityl-4H-1,2,4-triazol-1-ium Trifluoromethanesulfonate ([4a]OTf)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.18) yielded the product as an off-white powder in 58% yield (123 mg, 0.287 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 10.60 (s, 1H), 9.59 (s, 1H), 7.53–7.45 (m, 5H), 7.16 (s, 2H), 5.63 (s, 2H), 2.34 (s, 3H), 2.01 (s, 6H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 146.2, 145.4, 141.9, 135.1, 133.9, 131.6, 129.9, 129.7, 129.6, 129.1, 51.6, 21.14, 17.26. HRMS (ESI) calcd for [C18H20N3]+, 278.1652; observed, 278.1642.

4-Cyclohexyl-1-mesityl-4H-1,2,4-triazol-1-ium Trifluoromethanesulfonate ([4b]OTf)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.54) yielded the product as an off-white powder in 86% yield (181 mg, 0.431 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 10.55 (s, 1H), 9.56 (s, 1H), 7.17 (s, 2H), 4.48 (tt, J = 11.5, 3.8 Hz, 1H), 2.35 (s, 3H), 2.32–2.28 (m, 2H), 2.04 (s, 6H), 1.91–1.68 (m, 5H), 1.50–1.38 (m, 2H), 1.29–1.18 (m, 1H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 144.4, 143.5, 141.4, 134.8, 132.2, 129.4, 58.4, 31.8, 24.3, 24.2, 20.7, 16.8. HRMS (ESI) calcd for [C17H24N3]+, 270.1965; observed, 270.1959.

4-((3s,5s,7s)-Adamantan-1-yl)-1-mesityl-4H-1,2,4-triazol-1-ium Trifluoromethanesulfonate ([4c]OTf)

0.5 mmol Scale

The title compound was prepared according to general procedure 2b Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.56) yielded the product as an off-white powder in 75% yield (176 mg, 0.374 mmol).

8 mmol Scale

After evaporation of the reaction solvent, the crude product was dissolved in dichloromethane (50 mL), filtered, and crashed out with hexanes (70 mL), which yielded the pure product as a colorless powder in 77% yield (2.89 g, 6.13 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 10.65 (s, 1H), 9.81 (s, 1H), 7.18 (s, 1H), 2.35 (s, 3H), 2.28 (bs, 9H), 2.05 (s, 6H), 1.79–1.71 (m, 6H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 143.3, 142.7, 141.4, 134.8, 131.3, 129.4, 60.9, 41.3, 34.7, 28.9, 20.7, 16.9. HRMS (ESI) calcd for [C21H28N3]+, 322.2278; observed, 322.2273.

1-Mesityl-4-phenyl-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([4d]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; f = 0.36) yielded the product as an off-white powder in 52% yield (91 mg, 0.266 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.10 (s, 1H), 10.11 (s, 1H), 7.97 (d, J = 8.0 Hz, 2H), 7.78–7.74 (m, 2H), 7.69 (t, J = 7.4 Hz, 1H), 7.21 (s, 2H), 2.37 (s, 3H), 2.16 (s, 6H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 1143.8, 143.2, 141.6, 134.9, 132.2, 131.0, 130.7, 130.2, 129.5, 122.5, 20.7, 17.0. HRMS (ESI) calcd for [C17H18N3]+, 264.1495; observed, 264.1490.

1-Mesityl-4-phenyl-4H-1,2,4-triazol-1-ium Trifluoromethanesulfonate ([4d]OTf)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.19) yielded the product as an off-white powder in 74% yield (153 mg, 0.372 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.10 (s, 1H), 10.11 (s, 1H), 7.96 (d, J = 8.0 Hz, 2H), 7.78–7.74 (m, 2H), 7.69 (t, J = 7.4 Hz, 1H), 7.21 (s, 2H), 2.37 (s, 3H), 2.16 (s, 6H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 1143.8, 143.2, 141.6, 134.9, 132.2, 131.0, 130.6, 130.1, 129.5, 122.5, 20.7, 17.0. HRMS (ESI) calcd for [C17H18N3]+, 264.1495; observed, 264.1485.

1-Mesityl-4-(2-((4-methoxybenzyl)thio)phenyl)-4H-1,2,4-triazol-1-ium Trifluoromethanesulfonate ([4f]OTf)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; R = 48) yielded the product as a light brown oil (which solidified upon standing) in 59% yield (166 mg, 0.229 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 10.95 (s, 1H), 9.68 (s, 1H), 7.91 (dd, J = 7.9, 1.3 Hz, 1H), 7.88 (dd, J = 7.9, 1.3 Hz, 1H), 7.74 (td, J = 7.7, 1.3 Hz, 1H), 7.66 (td, J = 7.7, 1.3 Hz, 1H), 7.22 (s, 2H), 7.10 (d, J = 8.7 Hz, 2H), 6.83 (d, J = 8.7 Hz, 2H), 4.20 (s, 2H), 3.72 (s, 3H), 2.37 (s, 3H’), 2.13 (s, 6H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 158.6, 146.0, 145.6, 141.7, 134.8, 133.1, 132.7, 132.2, 131.8, 130.8, 129.9, 129.5, 128.5, 128.2, 127.7, 55.1, 38.3, 20.7, 17.0. HRMS (ESI) calcd for [C25H26N3OS]+, 416.1791; observed, 416.1766.

4-(4-Fluorophenyl)-1-mesityl-4H-1,2,4-triazol-1-ium Trifluoromethanesulfonate ([4i]OTf)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.47) yielded the product as a white powder in 54% yield (117 mg, 0.277 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.05 (s, 1H), 10.06 (s, 1H), 8.04–8.01 (m, 2H), 7.68–7.63 (m, 2H), 7.20 (s, 1H), 2.37 (s, 3H’), 2.15 (s, 6H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 162.7 (d, JC–F = 248.6 Hz), 144.0, 143.3, 141.6, 134.9, 131.0, 129.5, 128.7 (d, JC–F = 3.0 Hz), 125.3 (d, JC–F = 9.3 Hz), 117.1 (d, JC–F = 23.8 Hz), 20.7, 17.0. 19F{1H} NMR (376 MHz, DMSO-d6, 298 K, referenced to C6H5F): δ −77.85, −110.18. HRMS (ESI) calcd for [C17H17FN3]+, 282.1401; observed, 282.1393.

4-(4-Chlorophenyl)-1-mesityl-4H-1,2,4-triazol-1-ium Trifluoromethanesulfonate ([4k]OTf)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.43) yielded the product as an off-white powder in 58% yield (130 mg, 0.291 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.10 (s, 1H), 10.10 (s, 1H), 8.00 (d, J = 8.9 Hz, 2H), 7.88 (d, J = 8.9 Hz, 2H), 7.20 (s, 2H), 2.37 (s, 3H), 2.15 (s, 6H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 143.9, 143.3, 241.6, 135.2, 134.9, 131.2, 131.0, 130.1, 129.5, 124.5, 20.7, 17.0. HRMS (ESI) calcd for [C17H17ClN3]+, 298.1106; observed, 298.1101.

1-Mesityl-4-(pyridin-2-yl)-4H-1,2,4-triazol-1-ium Trifluoromethanesulfonate ([4l]OTf)

The title compound was prepared according to general procedure 2b. Purification by washing with hexanes (2 × 10 mL) and diethyl ether (2 × 10 mL), followed by recrystallization from dioxane, yielded the product as a colorless powder in 54% yield (112 mg, 0.271 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.37 (s, 1H), 10.30 (s, 1H), 8.74–8.73 (m, 1H), 8.34–8.30 (m, 1H), 8.12 (d, J = 8.2 Hz, 1H), 7.77–7.74 (m, 1H), 7.20 (s, 2H), 2.37 (s, 3H), 2.14 (s, 6H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 149.3, 145.0, 142.8, 142.6, 141.6, 140.6, 134.9, 131.1, 129.4, 126.0, 115.5, 20.7, 17.0. HRMS (ESI) calcd for [C16H17N4]+, 265.1448; observed, 265.1444.

4-Cyclohexyl-1-(naphthalen-1-yl)-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([5b]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.41) yielded the product as an off-white powder in 96% yield (175 mg, 0.478 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 10.78 (s, 1H), 9.69 (s, 1H), 8.32 (d, J = 8.3 Hz, 1H), 8.20–8.18 (m, 1H), 7.97–7.95 (m, 1H), 7.86–7.69 (m, 4H), 4.52 (tt, J = 11.6, 3.9 Hz, 1H), 2.37–2.33 (m, 2H), 1.94–1.70 (m, 5H), 1.51–1.44 (m, 2H), 1.30–1.20 (m, 1H’). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 144.0, 143.7, 133.7, 132.0, 131.2, 128.5, 128.3, 127.6, 127.1, 125.3, 125.1, 122.1, 58.4, 31.9, 24.4, 24.2. HRMS (ESI) calcd for [C18H14N3]+, 278.1652; observed, 278.1647.

1-(Naphthalen-1-yl)-4-phenyl-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([5d]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.19) yielded the product as a brown powder in 81% yield (145 mg, 0.406 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.36 (s, 1H), 10.15 (s, 1H), 8.37 (d, J = 8.4 Hz, 1H), 8.24–8.20 (m, 1H), 8.06–8.02 (m, 2H), 7.98 (d, J = 8.0 Hz, 2H), 7.85–7.70 (m, 6H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 143.7, 143.4, 133.7, 132.2 (2 signals), 131.0, 130.7, 130.3, 128.5, 128.4, 127.7, 127.1, 125.4, 125.2, 122.6, 122.3. HRMS (ESI) calcd for [C18H14N3]+, 272.1182; observed, 272.1173.

1-(4-Methoxyphenyl)-4-phenyl-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([6d]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.19) yielded the product as a pale brown powder in 91% yield (155 mg, 0.456 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.30 (s, 1H), 9.97 (s, 1H), 7.96–7.91 (m, 4H), 7.86–7.74 (m, 2H), 7.68 (t, J = 7.3 Hz, 1H), 7.29 (d, J = 9.1 Hz, 2H), 3.88 (s, 3H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 160.7, 143.1, 139.7, 132.1, 130.7, 130.3, 128.0, 122.5, 115.28, 55.8. HRMS (ESI) calcd for [C15H14N3O]+, 252.1131; observed, 252.1124.

1-(4-Methoxyphenyl)-4-(pyrimidin-2-yl)-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([6m]BF4)

The title compound was prepared according to general procedure 2b on a 3 mmol scale. After evaporation of the reaction solvent, the crude product was washed with hexanes (2 × 10 mL), diethyl ether (2 × 10 mL), and THF (3 × 5 mL). Extraction of the resulting solid with acetone (2 × 10 mL) yielded the desired product upon evaporation as a pale brown powder in 53% yield (273 mg, 0.798 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.69 (s, 1H), 10.27 (s, 1H), 9.16 (d, J = 4.5 Hz, 2H), 8.04 (d, J = 8.5 Hz, 2H), 7.89 (t, J = 4.5 Hz, 1H), 7.26 (d, J = 8.5 Hz, 2H), 3.88 (s, 3H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 160.9, 160.4, 151.0, 142.1, 139.2, 127.8, 123.3, 122.9, 115.2, 55.9. HRMS (ESI) calcd for [C15H14N3O]+, 254.1036; observed, 254.1035.

4-Phenyl-1-(3-(trifluoromethyl)phenyl)-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([7d]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.37) yielded the product as an off-white solid in 95% yield (178 mg, 0.473 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.59 (s, 1H), 10.08 (s, 1H), 8.45 (s, 1H), 8.37 (d, J = 8.0 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 8.03 (t, J = 8.0 Hz, 1H), 7.94 (d, J = 7.7 Hz, 2H), 7.81–7.77 (m, 2H), 7.73–7.70 (m, 1H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 143.2, 142.3, 135.3, 131.8, 130.6, 130.5 (q, J = 32.8 Hz), 130.2, 127.2 (q, J = 3.8 Hz), 124.8, 123.2 (q, J = 272.2 Hz), 122.3, 117.7 (q, J = 3.8 Hz). 19F{1H} NMR (376 MHz, DMSO-d6, 298 K, referenced to C6H5F): δ −61.42, −148.42. HRMS (ESI) calcd for [C15H14N3O]+, 290.0900; observed, 290.0891.

4-(2,6-Diisopropylphenyl)-1-(3-(trifluoromethyl)phenyl)-4H-1,2,4-triazol-1-ium Tetrafluoroborate ([7e]BF4)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.50) yielded the product as a pale yellow-green oil in 98% yield (226 mg, 0.489 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.48 (s, 1H), 9.98 (s, 1H), 8.43 (s, 1H), 8.39 (d, J = 8.0 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 8.02 (t, J = 8.0 Hz, 1H), 7.73 (t, J = 7.8 Hz, 1H), 7.55 (d, J = 7.8 Hz, 2H), 2.60 (sept, J = 6.7 Hz, 2H), 1.20 (d, J = 6.7 Hz, 6H), 1.15 (d, J = 8.0 Hz, 6H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 146.0, 145.5, 143.1, 135.8, 132.5, 131.5, 130.4 (q, J = 32.9 Hz), 127.2 (q, J = 3.7 Hz), 127.1, 125.1, 124.9, 123.4 (q, J = 272.6 Hz), 118.1 (q, J = 4.0 Hz). 19F{1H} NMR (376 MHz, DMSO-d6, 298 K, referenced to C6H5F): δ −61.37, −148.41. HRMS (ESI) calcd for [C15H14N3O]+, 374.1839; observed, 374.1827.

1-(4-Fluorophenyl)-4-phenyl-4H-1,2,4-triazol-1-ium Trifluoromethanesulfonate ([8d]OTf)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.11) yielded the product as an off-white powder in 74% yield (144 mg, 0.369 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.41 (s, 1H), 10.02 (s, 1H), 8.11–8.06 (m, 2H), 7.94–7.92 (m, 2H), 7.93 (d, J = 7.7 Hz, 2H), 7.79–7.75 (m, 2H), 7.70 (t, J = 7.3 Hz, 1H), 7.66–7.62 (m, 2H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 162.8 (d, J = 247.9 Hz), 143.3, 140.7, 132.0, 131.4 (d, J = 3.0 Hz), 130.8, 130.3, 123.5 (d, J = 9.3 Hz), 122.5, 117.4 (d, J = 24.0 Hz). 19F{1H} NMR (376 MHz, DMSO-d6, 298 K, referenced to C6H5F): δ −77.85, −109.86. HRMS (ESI) calcd for [C15H14N3O]+, 240.0932; observed, 240.0925.

4-(2,6-Diisopropylphenyl)-1-(4-fluorophenyl)-4H-1,2,4-triazol-1-ium Trifluoromethanesulfonate ([8e]OTf)

The title compound was prepared according to general procedure 2b. Purification by column chromatography (silica; 1. dichloromethane; 2. dichloromethane/acetone, 4:1; Rf = 0.44) yielded the product as an off-white solid in 91% yield (216 mg, 0.456 mmol). 1H NMR (400 MHz, DMSO-d6, 298 K): δ 11.34 (s, 1H), 9.93 (s, 1H), 8.13–8.10 (m, 2H), 7.72 (t, J = 7.8 Hz, 1H), 7.66–7.62 (m, 2H), 7.55 (t, J = 7.8 Hz, 2H), 2.58 (sept, J = 6.7 Hz, 2H), 1.20 (d, J = 6.7 Hz, 6H), 1.15 (d, J = 6.7 Hz, 6H). 13C{1H} NMR (100 MHz, DMSO-d6, 298 K): δ 162.8 (d, J = 248.9 Hz), 1146.0, 145.5, 142,2, 132.4, 131.7 (d, J = 3.0 Hz), 127.1, 124.9, 123.7 (d, J = 9.0 Hz), 122.3, 119.1, 117.0 (d, J = 24.0 Hz). 19F{1H} NMR (376 MHz, DMSO-d6, 298 K, referenced to C6H5F): δ −77.85, −109.94. HRMS (ESI) calcd for [C15H14N3O]+, 324.1871; observed, 324.1864.