Rh(II)-Catalyzed Transannulation of 1,2,4-Oxadiazole Derivatives with

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Cite This: J. Org. Chem. 2018, 83, 11232−11244

Rh(II)-Catalyzed Transannulation of 1,2,4-Oxadiazole Derivatives with 1‑Sulfonyl-1,2,3-triazoles: Regioselective Synthesis of 5‑Sulfonamidoimidazoles Julia O. Strelnikova, Nikolai V. Rostovskii, Galina L. Starova, Alexander F. Khlebnikov, and Mikhail S. Novikov* St. Petersburg State University, Institute of Chemistry, 7/9 Universitetskaya nab., St. Petersburg 199034, Russia Downloaded via KAOHSIUNG MEDICAL UNIV on September 21, 2018 at 08:26:48 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

S Supporting Information *

ABSTRACT: An effective method for the synthesis of fully substituted 5-sulfonamidoimidazoles by Rh(II)-catalyzed transannulation of 1,2,4-oxadiazole derivatives with Nsulfonyl-1,2,3-triazoles is reported. The reaction works well with both aromatic 1,2,4-oxadiazoles and 1,2,4-oxadiazol-5ones providing a flexible approach to N-(alkoxy/amino)carbonyl- and N-alkyl-substituted imidazoles. Both the disclosed reactions are completely regioselective and provide the first examples of a carbenoid-mediated transformation of N,N,O-heterocycles.

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INTRODUCTION The imidazole ring is one of the most abundant units encountered in compounds, which are highly relevant for medicinal1 and synthetic chemistry.2 Among functionally substituted imidazoles 5-amino, 5-acylamino and 5-sulfonamido derivatives deserve special attention.3 Thus, 5-aminoimidazole ribonucleotide (AIR) is a key intermediate in the biosynthesis of the purine ribonucleotides4 and thiamin (vitamin B1).5 The core of 5-aminoimidazole is presented in the structure of some bioactive compounds exhibiting antifungal, antiplatelet and adenosine A2A receptor antagonist activities (Scheme 1).6 5-Aminoimidazole-4-carboxamides were also shown to be promising for treating diseases mediated by a heat shock protein 90 (Hsp 90).7 Of the numerous methods used for the synthesis of tri- and tetra-substituted 1H-imidazoles,8 only a few can be employed for the preparation of 5-aminoimidazoles.6a,9−11 The limited scope of substituents that can be introduced into the imidazole ring and the poor availability of the starting materials motivated us to search for new approaches to these compounds. In the past few years, several impressive examples of the synthesis of pyridines12 and isoquinolines13 via the transannulation of 1,2,4-oxadiazole derivatives were reported. The synthetic availability of diversely substituted 1,2,4oxadiazoles14 and their 5-oxo derivatives was therefore an incentive for the search of ways to apply the transannulation strategy to prepare hardly accessible imidazole derivatives. There is an example of intramolecular transannulation of 1,2,4oxadiazoles with the tethered imine moiety leading to 1unsubstituted aminoimidazoles.15 Recently, several research groups reported the synthesis of 4-sulfonamidoimidazoles by intermolecular transannulation reactions of 1,2,4-oxadiazole © 2018 American Chemical Society

Scheme 1. Bioactive 5-Aminoimidazole Derivatives

derivatives with N-alkynyl sulfonamides.16 In particular, 4sulfonamidoimidazoles were prepared from 1,2,4-oxadiazoles 1 under gold(I) catalysis,16a as well as from oxadiazolones 2 under Tf2NH catalysis16b (Scheme 2, reaction A). Both reactions proceed via attack by nitrogen of the heterocycle (atom N2) onto the α-carbon atom of the alkyne to form exclusively 4-aminoimidazole derivatives and neither of them is applicable to the synthesis of regioisomeric 5-aminoimidazoles. In a search of suitable reaction partners for the 1,2,4oxadiazoles, which would provide the reverse regioselectivity of the transannulation, we considered 1-sulfonyl-1,2,3-triazoles Received: July 15, 2018 Published: July 30, 2018 11232

DOI: 10.1021/acs.joc.8b01809 J. Org. Chem. 2018, 83, 11232−11244

Article

The Journal of Organic Chemistry

Table 1. Optimization of Conditions for 4a Synthesisa

Scheme 2. Synthesis of 4- and 5-Aminoimidazoles from 1,2,4-Oxadiazole Derivatives

entry

catalystb

T (°C)

yield of 4a (%)c

1d 2d 3 4 5 6

Rh2(OAc)4 Rh2(Piv)4 Rh2(Piv)4 Rh2(esp)2 Rh2(Oct)4 Rh2(Piv)4

120 100 100 100 100 84

0 50 89 75 23 93 (91)e

a

Reaction conditions: addition of 3a (0.3 mmol) to a solution of 1a (0.1 mmol) in portions of 0.05 mmol. bPiv = pivalate, esp = α,α,α′,α′tetramethyl-1,3-benzenedipropanoate, Oct = octanoate. c1H NMR yields using CH2Br2 as an internal standard. dAddition of 3 equiv of 3a in one portion. eIsolated yield.

3.17 These compounds have recently been used as the precursors of α-imino Rh(II) carbenoids in the synthesis of aminofurans and aminopyrroles.18 Until the current year,19 reactions of both 1,2,4-oxadiazoles 1 and 1,2,4-oxadiazol-5-ones 2 with carbenoids were unknown, and the question as to whether carbenoids can transform these N,N,O-heterocycles remained open. In this work, we report a method for the synthesis of 5aminoimidazoles 4 and 5 by the intermolecular transannulation reaction of readily available 1,2,4-oxadiazole derivatives with 1-sulfonyl-1,2,3-triazoles under rhodium(II) catalysis (Scheme 2, reaction B).

triazole completely decomposed in the reaction, ca. 45% of 1a left unreacted (entry 2). This result inspired us to further optimize the reaction conditions. A drastic increase in the yield of 4a was observed, when the triazole was added in several portions. By this way, using Rh2(Piv)4, imidazole 4a was obtained in 89% yield, although there was still ca. 7% of unreacted 1a (entry 3). The use of Rh2(Oct)4 or Rh2(esp)2 also led to the formation of 4a although the yields were significantly lower (entries 4, 5). Further optimization (see Supporting Information) showed that the highest yield of 4a was achieved by the addition of 3 equiv of the triazole in 0.5 equiv portions to the oxadiazole solution in DCE at 84 °C with 5 mol % of Rh2(Piv)4 as a catalyst (entry 6). With the optimized conditions, we then explored the scope of the reaction using a series of 1,2,4-oxadiazoles 1 and 1sulfonyl-1,2,3-triazoles 3 (Scheme 4). It was found that the reaction tolerates both electron-donating and electron-withdrawing aryl substituents as well as naphthyl and benzyl groups at the C3 of 1,2,4-oxadiazole (imidazoles 4a−p). In contrast to the benzyl ester (imidazole 4q), which was synthesized in excellent yield, tert-butyl ester (imidazole 4r) could not be obtained, probably, due to its instability under the reaction conditions. Imidazole 4s bearing an amide function at the N1 position was also obtained in good yield. Various 4aryl-1-sulfonyl-1,2,3-triazoles were also suitable for the reaction and gave 5-aminoimidazoles 4t−z,za in good yields. 1-Mesyl-

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RESULTS AND DISCUSSION We began our study by exploring the reaction of 5-methoxy1,2,4-oxadiazole 1a and 1-sulfonyl-1,2,3-triazole 3a in the presence of rhodium(II) carboxylates (Scheme 3). In the molecule of oxadiazole 1a there are two nucleophilic nitrogen atoms that can be attacked by α-imino Rh(II) carbenoid, derived from triazole 3a, to give complexes 6 (route a) and 6′ (route b) respectively. We hoped the reaction would proceed by route a, since only complex 6 would produce the desired 5sulfonamidoimidazole 4a. An alternative pathway b would lead to the 4-amino-substituted isomer 4a′. Surprisingly when Rh2(OAc)4 was tested as a catalyst the conversion of the oxadiazole was not observed at all (Table 1, entry 1). The use of Rh2(Piv)4 in 1,2-dichloroethane (DCE) at 100 °C (3 equiv of the triazole in one portion) gave the desired 5-aminoimidazole 4a in 50% yield. Although the

Scheme 3. Possible Pathways for the Rh(II)-Catalyzed Reaction of Oxadiazole 1a with Triazole 3a

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The Journal of Organic Chemistry Scheme 4. Scope of Imidazole-1-carboxylatesa

Reaction conditions: 1 (0.2 mmol), 3 (0.6 mmol), Rh2(Piv)4 (5 mol %), DCE (0.5 mL), 84 °C, 30 min. b3 (0.5 mmol). c3 (0.4 mmol). d3 (0.8 mmol). a

the reaction toward the nature of the aryl and sulfonyl substituents in the triazole. It should be noted that in many cases imidazoles 4 and 5 can be isolated and purified without chromatography. The structures of all synthesized compounds were verified by 1H and 13C NMR spectroscopy and HRMS. The structures of imidazole-1-carboxylate 4e and 1-methylimidazole 5a were confirmed by X-ray diffraction analysis (Scheme 4, 5).20 To test whether the reaction could be scaled-up, a gramscale synthesis of 1-methylimidazole 5e was carried out with a reduced loading of Rh2(Piv)4 (1 mol %). As the result, imidazole 5e was isolated in analytically pure form in good yield (84%, 1.11 g) without chromatographic purification. The plausible pathways for the formation of imidazoles 4/5 from 1,2,4-oxadiazoles 1/1,2,4-oxadiazol-5-ones 2 and 1sulfonyl-1,2,3-triazoles 3 are depicted in Scheme 6. α-Imino rhodium carbenoid 7, generated from triazole 3a and Rh2(Piv)4, adds to the nitrogen atom (N2) of oxadiazole 1a to give complex 6. The conversion of complex 6 to 1,3,6-

1,2,3-triazole 3g afforded the corresponding imidazole 4y in slightly lower yield and 4 equiv of the triazole were required for full conversion of the oxadiazole. Next we studied the reactivity of 4-alkyl-1,2,4-oxadiazol-5ones 2 toward 1-sulfonyl-1,2,3-triazoles 3 under Rh(II) catalysis (Scheme 5). Oxadiazolone 2a (R1 = Me, R2 = Ph), like oxadiazole 1a, did not react with triazole 3a in the presence of Rh2(OAc)4 under the standard reaction conditions (DCE, 84 °C). When Rh2(OAc)4 was replaced by Rh2(Piv)4 (5 mol %), however, the reaction was completed in several minutes, giving N-methylated imidazole 5a (Scheme 5). In contrast to the similar reaction of 1a, only 1.2 equiv of triazole 3a were required for full conversion of oxadiazolone 2a. Under these conditions 1-methylimidazoles 5a−k were synthesized in excellent yields from various 3-aryl- and 3-alkyl-substituted 1,2,4-oxadiazol-5-ones 2. 1-Benzylimidazole 5l was also obtained in 94% yield. The high yields of imidazoles 5m−s derived from different 4-aryl-1sulfonyl-1,2,3-triazoles 3 pointed to a rather low sensitivity of 11234


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The Journal of Organic Chemistry Scheme 5. Scope of 1-Alkylimidazolesa

Reaction conditions: 2 (0.2 mmol), 3 (0.24 mmol), Rh2(Piv)4 (5 mol %), DCE (0.5 mL), 84 °C, 5 min.

a

triazatriene 8a (R = CO2Me) likely occurs in a one-step via simultaneous cleavage of the C−Rh and N−O bonds. The reaction of carbenoid 7 with 1,2,4-oxadiazol-5-one 2a can proceed in a similar manner via the intermediate formation of complex 9. The decarboxylation of betaine 10 which is formed after ring opening of 9 produces the 1,3,6-triazahexa1,3,5-triene intermediate 8b (R = Me). The subsequent 5-exotrig-cyclization of intermediates 8 and prototropic shift leads to imidazoles 4a and 5a. It is worthy of note that in contrast to 3aza-,21 1,4-diaza-18b−e,22 and 1,5-diazahexa-1,3,5-trienes,23 the generation of 1,3,6-triazahexa-1,3,5-triene species has never been reported earlier. Triazahexatrienes 8 can, in principle, undergo two competing 1,5-cyclizations leading either to 4Himidazolium betaines 11 (the N1−C5 bond formation) or their 2H-regioisomers (not shown) (the C2−N6 bond formation). The obtained results showed that triazahexatrienes 8 cyclize into 4H-imidazolium betaines exclusively, but not their 2H regioisomers, even in the case of triazatriene 8a with the electron-withdrawing N1-substituent (R = CO2Me). It is known that some 5-aminoimidazole-1-carboxylates at elevated temperatures can undergo isomerization via ester group transfer from the endocyclic to the exocyclic nitrogen atom.24 Unexpectedly, it was found that at 190−200 °C 1methoxycarbonyl-substituted imidazoles 4 undergo decarbox-

Scheme 6. Proposed Mechanisms for the Formation of Imidazoles 4, 5

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3-Phenyl-1,2,4-oxadiazol-5(4H)-one (A).13 White solid (1.17 g, yield 72%). mp 195−196 °C. 1H NMR (DMSO-d6) δ 13.19 (br. s, 1H), 7.90−7.83 (m, 2H), 7.65−7.54 (m, 3H). 13C NMR (DMSO-d6) δ 160.4, 157.9, 132.7, 129.7, 126.6, 123.8. HRMS−ESI [M + H]+ calcd for C8H7N2O2+, 163.0502, found 163.0500. 3-(4-Methylphenyl)-1,2,4-oxadiazol-5(4H)-one (B).13 White solid (1.23 g, yield 70%). mp 221−223 °C. 1H NMR (DMSO-d6) δ 12.92 (br. s, 1H), 7.71 (d, J = 8.1 Hz, 2H), 7.37 (d, J = 8.1 Hz, 2H), 2.37 (s, 3H). 13C NMR (DMSO-d6) δ 160.5, 157.9, 142.8, 130.3, 126.5, 121.0, 21.6. HRMS−ESI [M + Na]+ calcd for C9H8N2NaO2+, 199.0478, found 199.0484. 3-(2-Methylphenyl)-1,2,4-oxadiazol-5(4H)-one (C).33 White solid (1.09 g, yield 62%). mp 156−157 °C. 1H NMR (DMSO-d6) δ 12.66 (br. s, 1H), 7.57 (dd, J = 7.7, 1.3 Hz, 1H), 7.51 (td, J = 7.6 Hz, 1H), 7.44−7.35 (m, 2H), 2.46 (s, 3H). 13C NMR (DMSO-d6) δ 160.1, 158.5, 137.8, 132.0, 131.9, 129.4, 126.7, 123.3, 21.0. HRMS−ESI [M + Na]+ calcd for C9H8N2NaO2+, 199.0478, found 199.0477. 3-(4-Methoxyphenyl)-1,2,4-oxadiazol-5(4H)-one (D).13 White solid (1.31 g, yield 68%). mp 209−211 °C. 1H NMR (DMSO-d6) δ 12.79 (br. s, 1H), 7.75 (d, J = 7.9 Hz, 2H), 7.12 (d, J = 7.9 Hz, 2H), 3.83 (s, 3H). 13C NMR (DMSO-d6) δ 162.6, 160.5, 157.5, 128.3, 115.9, 115.2, 56.0. HRMS−ESI [M + Na]+ calcd for C9H8N2NaO3+, 215.0427, found 215.0437. 3-(4-Fluorophenyl)-1,2,4-oxadiazol-5(4H)-one (E).13 White solid (1.03 g, yield 57%). mp 228−229 °C. 1H NMR (DMSO-d6) δ 13.14 (br. s, 1H), 7.94−7.88 (m, 2H), 7.46−7.39 (m, 2H). 13C NMR (DMSO-d6) δ 164.7 (d, J = 250.4 Hz), 160.4, 157.1, 129.3 (d, J = 9.1 Hz), 120.4 (d, J = 3.0 Hz), 117.0 (d, J = 22.4 Hz). HRMS−ESI [M + Na]+ calcd for C8H5FN2NaO2+, 203.0227, found 203.0234. 3-(3-Fluorophenyl)-1,2,4-oxadiazol-5(4H)-one (F). White solid (1.01 g, yield 56%). mp 188−189 °C. 1H NMR (DMSO-d6) δ 13.39 (br. s, 1H), 7.76−7.70 (m, 2H), 7.66−7.59 (m, 1H), 7.51−7.44 (m, 1H). 13C NMR (DMSO-d6) δ 162.6 (d, J = 245.1 Hz), 160.3, 157.1 (d, J = 3.0 Hz), 132.1 (d, J = 8.5 Hz), 125.9 (d, J = 8.8 Hz), 122.9 (d, J = 3.1 Hz), 119.6 (d, J = 21.1 Hz), 113.7 (d, J = 24.5 Hz). HRMS−ESI [M + Na]+ calcd for C8H5FN2NaO2+, 203.0227, found 203.0234. 3-(4-Chlorophenyl)-1,2,4-oxadiazol-5(4H)-one (G).13 White solid (1.24 g, yield 63%). mp 280−282 °C. 1H NMR (DMSO-d6) δ 13.04 (br. s, 1H), 7.86−7.80 (m, 2H), 7.70−7.64 (m, 2H). 13C NMR (DMSO-d6) δ 160.3, 157.1, 137.4, 130.0, 128.3, 122.7. HRMS−ESI [M + Na]+ calcd for C8H535ClN2NaO2+, 218.9932, found 218.9940. 3-(3-Chlorophenyl)-1,2,4-oxadiazol-5(4H)-one (H). White solid (1.06 g, yield 54%). mp 185−186 °C. 1H NMR (DMSO-d6) δ 13.02 (br. s, 1H), 7.87−7.56 (m, 4H). 13C NMR (DMSO-d6) δ 160.2, 156.8, 134.4, 132.5, 131.7, 126.3, 125.8, 125.2. HRMS−ESI [M + H]+ calcd for C8H635ClN2O2+, 197.0112, found 197.0118. 3-(4-Bromophenyl)-1,2,4-oxadiazol-5(4H)-one (I).33 White solid (1.44 g, yield 60%). mp 291−293 °C. 1H NMR (DMSO-d6) δ 13.03 (br. s, 1H), 7.84−7.71 (m, 4H). 13C NMR (DMSO-d6) δ 160.3, 157.2, 132.9, 128.4, 126.3, 123.0. HRMS−ESI [M + Na]+ calcd for C8H579BrN2NaO2+, 262.9427, found 262.9438. 3-[4-(Trifluoromethyl)phenyl]-1,2,4-oxadiazol-5(4H)-one (J).13 White solid (1.27 g, yield 55%). mp 267−269 °C. 1H NMR (DMSO-d6) δ 13.23 (br. s, 1H), 8.03 (d, J = 8.3 Hz, 2H), 7.97 (d, J = 8.3 Hz, 2H). 13C NMR (DMSO-d6) δ 160.3, 157.0, 132.3 (q, J = 32.2 Hz), 127.8 (q, J = 0.9 Hz), 127.5, 126.7 (q, J = 3.9 Hz), 124.1 (q, J = 272.6 Hz). HRMS−ESI [M + Na]+ calcd for C9H5F3N2NaO2+, 253.0195, found 253.0202. 3-[3-(Trifluoromethyl)phenyl]-1,2,4-oxadiazol-5(4H)-one (K).13 White solid (1.43 g, yield 62%). mp 171−173 °C. 1H NMR (DMSO-d6) δ 13.46 (br. s, 1H), 8.24−8.16 (m, 2H), 8.02−7.95 (m, 1H), 7.86−7.79 (m, 1H). 13C NMR (DMSO-d6) δ 160.2, 157.0, 131.1, 130.6, 130.4 (q, J = 32.5 Hz), 129.1 (q, J = 3.6 Hz), 125.0, 124.1 (q, J = 272.6 Hz), 123.5. HRMS−ESI [M + Na]+ calcd for C9H5F3N2NaO2+, 253.0195, found 253.0200. 3-(4-Nitrophenyl)-1,2,4-oxadiazol-5(4H)-one (L).13 Yellow solid (1.20 g, yield 58%). mp 304−306 °C (dec.). 1H NMR (DMSO-d6) δ 13.37 (br. s, 1H), 8.41 (d, J = 8.9 Hz, 2H), 8.09 (d, J = 8.9 Hz, 2H). 13 C NMR (DMSO-d6) δ 160.2, 156.7, 149.9, 129.6, 128.1, 124.9.

ylation with simultaneous transfer of a methyl group to sulfonamide nitrogen. Thus, imidazole 4g, when heated at its melting point, gave imidazole 12 in good yield. The plausible mechanism of this unusual decarboxylative reaction is depicted in Scheme 7. Scheme 7. Formation of NH-Imidazole 12

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CONCLUSION In conclusion, we have developed a convenient synthesis of fully substituted 5-sulfonamidoimidazoles by Rh2(Piv)4-catalyzed transannulation of 1,2,4-oxadiazole derivatives with Nsulfonyl-1,2,3-triazoles. The flexibility of the method, which efficiently works with both 1,2,4-oxadiazoles and 1,2,4oxadiazol-5-ones, allows the introduction of various substituents in all positions of the imidazole ring. The new method provides high yields of imidazoles with alkyl, ester or amide groups at the N1 position, and these can be isolated in many cases in a chromatography-free manner. The smooth formation of 5-sulfonamidoimidazoles in both reactions is ensured by the regioselectivity of the two key stages of the domino sequences, namely, carbenoid-mediated oxadiazole ring opening and 5exo-trig-cyclization of 1,3,6-triazahexatriene intermediate.

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EXPERIMENTAL SECTION

General Methods. Melting points were determined on a melting point apparatus and are uncorrected. 1H (400 MHz) and 13C (100 MHz) NMR spectra were recorded in solvents indicated below. Chemical shifts (δ) are reported in parts per million downfield from tetramethylsilane. High-resolution mass spectra were recorded on an HRMS-ESI-QTOF instrument, electrospray ionization, positive mode. Thin-layer chromatography (TLC) was conducted on aluminum sheets precoated with SiO2 ALUGRAM SIL G/UV254. Column chromatography was performed on silica gel 60 M (0.04− 0.063 mm). 1,2-Dichloroethane was washed with concentrated H2SO4 and water, distilled from P2O5, and stored over anhydrous K2CO3. Tetrahydrofuran was distilled and stored over sodium metal. DMSO was purchased and used without further purification. The catalysts Rh2(Oct)4,25 Rh2(Piv)4,26 and Rh2(esp)227 were prepared by the reported procedures and gave satisfactory elemental analyses. 3-(4Bromophenyl)-N,N-dimethyl-1,2,4-oxadiazol-5-amine (1s),28 4-benzyl-3-phenyl-1,2,4-oxadiazol-5(4H)-one (2q),16b and triazoles 3a− e,g−i29 were synthesized according to the published procedures and they have full characterization data. 5-Methoxy-1,2,4-oxadiazoles 130 and 4-methyl-1,2,4-oxadiazol-5(4H)-ones 216b,31 can be prepared in good to high yields according to the reported procedures. In this work, both these compounds were synthesized from the common precursor, 1,2,4-oxadiazol-5(4H)-ones A−P, and diazomethane. This procedure provided sufficient yields of the targeted compounds 1 and 2 in a single synthetic operation. General Procedure for the Preparation of 1,2,4-Oxadiazol5(4H)-ones A−P.32 To a solution of amidoxime (10 mmol) and dimethyl carbonate (15 mmol) in DMSO (10 mL) 600 mg (15 mmol) powdered NaOH was rapidly added. The reaction mixture was stirred at room temperature for 4 h and then diluted with cold water (10 mL). Concentrated HCl (15 mL) was added dropwise to the mixture. The resulting precipitate of oxadiazolone was filtered off, washed with water (10 mL) and dried in air at 50 °C. 11236


Article

The Journal of Organic Chemistry HRMS−ESI [M − H]− calcd for C8H4N3O4−, 206.0207, found 206.0197. 3-(Naphthalen-1-yl)-1,2,4-oxadiazol-5(4H)-one (M). White solid (1.80 g, yield 85%). mp 184−186 °C. 1H NMR (DMSO-d6) δ 12.95 (br. s, 1H), 8.48 (d, J = 8.1 Hz, 1H), 8.21 (d, J = 8.2 Hz, 1H), 8.09 (d, J = 8.2 Hz, 1H), 7.94−7.87 (m, 1H), 7.74−7.63 (m, 3H). 13C NMR (DMSO-d6) δ 160.1, 158.3, 133.8, 132.9, 129.9, 129.2, 129.1, 128.5, 127.4, 125.6, 125.5, 120.8. HRMS−ESI [M + Na]+ calcd for C12H8N2NaO2+, 235.0478, found 235.0489. 3-(Naphthalen-2-yl)-1,2,4-oxadiazol-5(4H)-one (N).13 White solid (1.38 g, yield 65%). mp 212−214 °C. 1H NMR (DMSO-d6) δ 13.08 (br. s, 1H), 8.42 (d, J = 1.7 Hz, 1H), 8.09 (d, J = 8.7 Hz, 1H), 8.04−7.99 (m, 2H), 7.87 (dd, J = 8.7, 1.7 Hz, 1H), 7.70−7.61 (m, 2H). 13C NMR (DMSO-d6) δ 160.4, 157.9, 134.8, 132.7, 129.6, 129.2, 128.8, 128.4, 127.9, 127.3, 122.5, 121.2. HRMS−ESI [M + Na]+ calcd for C12H8N2NaO2+, 235.0478, found 235.0489. 3-Benzyl-1,2,4-oxadiazol-5(4H)-one (O).34 Obtained according to the general procedure. After the addition of concentrated HCl the reaction mixture was extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The precipitated solid was filtered off, washed with Et2O and dried in air. White solid (581 mg, yield 33%). mp 104−106 °C. 1H NMR (CDCl3) δ 8.93 (br. s, 1H), 7.41−7.26 (m, 5H), 3.87 (s, 2H). 13C NMR (CDCl3) δ 161.3, 158.3, 132.2, 129.3, 128.8, 128.2, 31.6. HRMS−ESI [M + Na]+ calcd for C9H8N2NaO2+, 199.0478, found 199.0483. 3-(3-Methoxybenzyl)-1,2,4-oxadiazol-5(4H)-one (P). Obtained according to the general procedure. After the addition of concentrated HCl the reaction mixture was extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The precipitated solid was filtered off, washed with Et2O and dried in air. White solid (1.34 g, yield 65%). mp 89−91 °C. 1H NMR (DMSO-d6) δ 12.28 (br. s, 1H), 7.27 (t, J = 7.8 Hz, 1H), 6.90−6.84 (m, 3H), 3.84 (s, 2H), 3.75 (s, 3H). 13C NMR (DMSO-d6) δ 160.3, 159.9, 159.4, 135.7, 130.3, 121.4, 115.1, 113.3, 55.5, 31.1. HRMS−ESI [M + Na]+ calcd for C10H10N2NaO3+, 229.0584, found 229.0592. General Procedure for the Preparation of 5-Methoxy-1,2,4oxadiazoles 1 and 4-Methyl-1,2,4-oxadiazol-5(4H)-ones 2.35 To a stirred solution of diazomethane in Et2O (10 mL), prepared from N-methyl-N-nitrosourea (10 mmol) and KOH (46 mmol), 1,2,4-oxadiazol-5(4H)-one A−P (5 mmol) was slowly added in small portions at 0 °C. The resulting mixture was stirred at room temperature for 2 h and then carefully concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluent petroleum ether−Et2O 3:1) to give 5-methoxy-1,2,4-oxadiazole 1 and 4-methyl-1,2,4-oxadiazol-5(4H)-one 2. 5-Methoxy-3-phenyl-1,2,4-oxadiazole (1a)30 and 4-Methyl-3phenyl-1,2,4-oxadiazol-5(4H)-one (2a).16b Title compounds were obtained according to the general procedure from oxadiazolone A. Compound 1a. White solid (326 mg, yield 37%). mp 35−37 °C. Rf = 0.55 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 8.06−8.02 (m, 2H), 7.55−7.45 (m, 3H), 4.29 (s, 3H). 13C NMR (CDCl3) δ 174.0, 168.9, 131.2, 128.7, 127.1, 127.0, 60.2. HRMS−ESI [M + H]+ calcd for C9H9N2O2+, 177.0659, found 177.0658. Compound 2a. White solid (546 mg, yield 62%). mp 114−116 °C. Rf = 0.11 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 7.68−7.54 (m, 5H), 3.34 (s, 3H). 13C NMR (CDCl3) δ 159.7, 158.7, 132.1, 129.4, 128.1, 123.2, 29.7. HRMS−ESI [M + H]+ calcd for C9H9N2O2+, 177.0659, found 177.0657. 5-Methoxy-3-(4-methylphenyl)-1,2,4-oxadiazole (1b)30 and 4Methyl-3-(4-methylphenyl)-1,2,4-oxadiazol-5(4H)-one (2b).31 Title compounds were obtained according to the general procedure from oxadiazolone B. Compound 1b. White solid (409 mg, yield 43%). mp 35−37 °C. Rf = 0.55 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 7.92 (d, J = 8.2 Hz, 2H), 7.31−7.27 (m, 2H), 4.28 (s, 3H), 2.43 (s, 3H). 13C NMR (CDCl3) δ 173.9, 168.9, 141.5, 129.4, 127.0, 124.3, 60.2, 21.5. HRMS−ESI [M + Na]+ calcd for C10H10N2NaO2+, 213.0634, found 213.0644.

Compound 2b. White solid (485 mg, yield 51%). mp 98−99 °C. Rf = 0.12 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 7.52 (d, J = 8.1 Hz, 2H), 7.38 (d, J = 8.1 Hz, 2H), 3.33 (s, 3H), 2.47 (s, 3H). 13C NMR (CDCl3) δ 159.8, 158.8, 142.8, 130.0, 128.0, 120.3, 29.7, 21.5. HRMS−ESI [M + Na]+ calcd for C10H10N2NaO2+, 213.0634, found 213.0642. 5-Methoxy-3-(2-methylphenyl)-1,2,4-oxadiazole (1c) and 4Methyl-3-(2-methylphenyl)-1,2,4-oxadiazol-5(4H)-one (2c). Title compounds were obtained according to the general procedure from oxadiazolone C. Compound 1c. White solid (371 mg, yield 39%). mp 53−55 °C. Rf = 0.63 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 7.97−7.92 (m, 1H), 7.43−7.37 (m, 1H), 7.34−7.29 (m, 2H), 4.28 (s, 3H), 2.64 (s, 3H). 13 C NMR (CDCl3) δ 173.4, 169.8, 138.1, 131.3, 130.5, 129.9, 126.4, 125.9, 60.2, 22.0. HRMS−ESI [M + Na]+ calcd for C10H10N2NaO2+, 213.0634, found 213.0638. Compound 2c. Colorless oil (551 mg, yield 58%). Rf = 0.14 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 7.55−7.49 (m, 1H), 7.43− 7.33 (m, 3H), 3.10 (s, 3H), 2.37 (s, 3H). 13C NMR (CDCl3) δ 159.5, 158.8, 137.9, 131.9, 131.1, 129.6, 126.5, 122.6, 28.8, 19.4. HRMS− ESI [M + Na]+ calcd for C10H10N2NaO2+, 213.0634, found 213.0624. 5-Methoxy-3-(4-methoxyphenyl)-1,2,4-oxadiazole (1d) and 3(4-Methoxyphenyl)-4-methyl-1,2,4-oxadiazol-5(4H)-one (2d).16b Title compounds were obtained according to the general procedure from oxadiazolone D. Compound 1d. White solid (402 mg, yield 39%). mp 72−73 °C. Rf = 0.49 (hexane−Et2O, 1:1). 1H NMR (CDCl3) δ 8.00−7.95 (m, 2H), 7.02−6.97 (m, 2H), 4.28 (s, 3H), 3.89 (s, 3H). 13C NMR (CDCl3) δ 173.8, 168.7, 162.0, 128.7, 119.6, 114.1, 60.2, 55.4. HRMS−ESI [M + H]+ calcd for C10H11N2O3+, 207.0764, found 207.0771. Compound 2d. White solid (608 mg, yield 59%). mp 94−95 °C. Rf = 0.11 (hexane−Et2O, 1:1). 1H NMR (CDCl3) δ 7.60−7.54 (m, 2H), 7.10−7.04 (m, 2H), 3.90 (s, 3H), 3.33 (s, 3H). 13C NMR (CDCl3) δ 162.5, 159.8, 158.5, 129.7, 115.2, 114.8, 55.5, 29.7. HRMS−ESI [M + Na]+ calcd for C10H10N2NaO3+, 229.0584, found 229.0574. 3-(4-Fluorophenyl)-5-methoxy-1,2,4-oxadiazole (1e). This compound was obtained according to the general procedure from oxadiazolone E. White solid (330 mg, yield 34%). mp 41−42 °C. Rf = 0.53 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 8.06−8.01 (m, 2H), 7.21−7.13 (m, 2H), 4.29 (s, 3H). 13C NMR (CDCl3) δ 174.0, 168.1, 164.6 (d, J = 251.3 Hz), 129.2 (d, J = 8.8 Hz), 123.4 (d, J = 3.2 Hz), 115.9 (d, J = 22.0 Hz), 60.3. HRMS−ESI [M + H]+ calcd for C9H8FN2O2+, 195.0564, found 195.0571. The corresponding 4methyl-1,2,4-oxadiazolone was not isolated. 3-(3-Fluorophenyl)-5-methoxy-1,2,4-oxadiazole (1f). This compound was obtained according to the general procedure from oxadiazolone F. White solid (340 mg, yield 35%). mp 48−50 °C. Rf = 0.59 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 7.86−7.81 (dt, J = 7.7, 1.2 Hz, 1H), 7.74 (ddd, J = 9.5, 2.6, 1.5 Hz, 1H), 7.46 (td, J = 8.0, 5.7 Hz, 1H), 7.22 (tdd, J = 8.4, 2.6, 0.9 Hz, 1H), 4.30 (s, 3H). 13C NMR (CDCl3) δ 174.1, 168.1 (d, J = 3.0 Hz), 162.8 (d, J = 247.0 Hz), 130.4 (d, J = 8.1 Hz), 129.2 (d, J = 8.3 Hz), 122.7 (d, J = 3.3 Hz), 118.2 (d, J = 21.1 Hz), 114.2 (d, J = 23.9 Hz), 60.4. HRMS−ESI [M + H]+ calcd for C9H8FN2O2+, 195.0564, found 195.0568. The corresponding 4-methyl-1,2,4-oxadiazolone was not isolated. 3-(4-Chlorophenyl)-5-methoxy-1,2,4-oxadiazole (1g) and 3-(4Chlorophenyl)-4-methyl-1,2,4-oxadiazol-5(4H)-one (2g).16b Title compounds were obtained according to the general procedure from oxadiazolone G. Compound 1g. White solid (525 mg, yield 50%). mp 75−76 °C. Rf = 0.54 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 7.97 (d, J = 8.5 Hz, 2H), 7.45 (d, J = 8.5 Hz, 2H), 4.28 (s, 3H). 13C NMR (CDCl3) δ 174.1, 168.1, 137.3, 129.0, 128.4, 125.6, 60.3. HRMS−ESI [M + Ag]+ calcd for C9H7107Ag35ClN2O2+, 316.9241, found 316.9256. Compound 2g. White solid (515 mg, yield 49%). mp 116−118 °C. Rf = 0.09 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 7.62−7.55 (m, 4H), 3.35 (s, 3H). 13C NMR (CDCl3) δ 159.6, 157.9, 138.7, 129.8, 129.4, 121.7, 29.7. HRMS−ESI [M + Na] + calcd for C9H735ClN2NaO2+, 233.0088, found 233.0080. 11237


Article

The Journal of Organic Chemistry 3-(3-Chlorophenyl)-5-methoxy-1,2,4-oxadiazole (1h). This compound was obtained according to the general procedure from oxadiazolone H. White solid (515 mg, yield 49%). mp 49−50 °C. Rf = 0.59 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 8.05−8.02 (m, 1H), 7.94−7.90 (m, 1H), 7.51−7.47 (m, 1H), 7.42 (t, J = 7.8 Hz, 1H), 4.29 (s, 3H). 13C NMR (CDCl3) δ 174.1, 167.9, 134.8, 131.2, 130.0, 128.8, 127.2, 125.0, 60.4. HRMS−ESI [M + H]+ calcd for C9H835ClN2O2+, 211.0269, found 211.0272. The corresponding 4methyl-1,2,4-oxadiazolone was not isolated. 3-(4-Bromophenyl)-5-methoxy-1,2,4-oxadiazole (1i). This compound was obtained according to the general procedure from oxadiazolone I. White solid (610 mg, yield 48%). mp 76−77 °C. Rf = 0.59 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 7.93−7.87 (m, 2H), 7.65−7.59 (m, 2H), 4.28 (s, 3H). 13C NMR (CDCl3) δ 174.1, 168.2, 132.0, 128.6, 126.1, 125.7, 60.3. HRMS−ESI [M + Na]+ calcd for C9H779BrN2NaO2+, 276.9583, found 276.9571. The corresponding 4methyl-1,2,4-oxadiazolone was not isolated. 5-Methoxy-3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazole (1j) and 4-Methyl-3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5(4H)one (2j). Title compounds were obtained according to the general procedure from oxadiazolone J. Compound 1j. White solid (634 mg, yield 52%). mp 38−40 °C. Rf = 0.62 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 8.16 (d, J = 8.2 Hz, 2H), 7.75 (d, J = 8.2 Hz, 2H), 4.31 (s, 3H). 13C NMR (CDCl3) δ 174.3, 167.9, 132.9 (q, J = 32.7 Hz), 130.5, 127.4, 125.7 (q, J = 3.8 Hz), 123.8 (q, J = 272.5 Hz), 60.5. HRMS−ESI [M + H]+ calcd for C10H8F3N2O2+, 245.0532, found 245.0544. Compound 2j. White solid (537 mg, yield 44%). mp 61−62 °C. Rf = 0.11 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 7.87 (d, J = 8.3 Hz, 2H), 7.80 (d, J = 8.3 Hz, 2H), 3.38 (s, 3H). 13C NMR (CDCl3) δ 159.5, 157.6, 134.1 (q, J = 33.1 Hz), 128.7, 126.8, 126.5 (q, J = 3.6 Hz), 123.3 (q, J = 272.7 Hz), 29.8. HRMS−ESI [M + Na]+ calcd for C10H7F3N2NaO2+, 267.0352, found 267.0363. 5-Methoxy-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole (1k). This compound was obtained according to the general procedure from oxadiazolone K. White solid (622 mg, yield 51%). mp 30−31 °C. Rf = 0.50 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 8.31 (br. s, 1H), 8.23 (d, J = 7.8 Hz, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.63 (t, J = 7.8 Hz, 1H), 4.32 (s, 3H). 13C NMR (CDCl3) δ 174.3, 167.9, 131.4 (q, J = 32.8 Hz), 130.1, 129.3, 128.0, 127.8 (q, J = 3.7 Hz), 124.1 (q, J = 3.8 Hz), 123.7 (q, J = 272.6 Hz), 60.5. HRMS−ESI [M + H]+ calcd for C10H8F3N2O2+, 245.0532, found 245.0525. The corresponding 4-methyl-1,2,4-oxadiazolone was not isolated. 5-Methoxy-3-(4-nitrophenyl)-1,2,4-oxadiazole (1l) and 4-Methyl-3-(4-nitrophenyl)-1,2,4-oxadiazol-5(4H)-one (2l). Title compounds were obtained according to the general procedure from oxadiazolone L. Compound 1l. Yellow solid (464 mg, yield 42%). mp 106−108 °C. Rf = 0.50 (hexane−Et2O, 1:1). 1H NMR (CDCl3) δ 8.35 (d, J = 8.9 Hz, 2H), 8.23 (d, J = 8.9 Hz, 2H), 4.33 (s, 3H). 13C NMR (CDCl3) δ 174.4, 167.3, 149.5, 133.0, 128.0, 124.0, 60.6. HRMS−ESI [M + Na]+ calcd for C9H7N3NaO4+, 244.0329, found 244.0339. Compound 2l. Yellow solid (530 mg, yield 48%). mp 134−135 °C. Rf = 0.07 (hexane−Et2O, 1:1). 1H NMR (CDCl3) δ 8.46 (d, J = 8.9 Hz, 2H), 7.89 (d, J = 8.9 Hz, 2H), 3.41 (s, 3H). 13C NMR (CDCl3) δ 159.3, 157.1, 149.9, 129.4, 129.1, 124.5, 29.9. HRMS−ESI [M + Na]+ calcd for C9H7N3NaO4+, 244.0329, found 244.0335. 5-Methoxy-3-(naphthalen-1-yl)-1,2,4-oxadiazole (1m) and 4Methyl-3-(naphthalen-1-yl)-1,2,4-oxadiazol-5(4H)-one (2m).16b Title compounds were obtained according to the general procedure from oxadiazolone M. Compound 1m. White solid (418 mg, yield 37%). mp 43−44 °C. Rf = 0.46 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 8.91 (d, J = 8.6 Hz, 1H), 8.22 (d, J = 7.2 Hz, 1H), 8.02 (d, J = 8.2 Hz, 1H), 7.94 (d, J = 8.1 Hz, 1H), 7.68−7.62 (m, 1H), 7.61−7.55 (m, 2H), 4.34 (s, 3H). 13 C NMR (CDCl3) δ 173.5, 169.6, 133.9, 131.8, 130.5, 129.2, 128.6, 127.5, 126.3, 126.2, 125.0, 124.1, 60.3. HRMS−ESI [M + H]+ calcd for C13H11N2O2+, 227.0815, found 227.0825. Compound 2m. White solid (633 mg, yield 56%). mp 58−60 °C. Rf = 0.09 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 8.17−8.10 (m,

1H), 8.04−7.97 (m, 1H), 7.81−7.75 (m, 1H), 7.70−7.61 (m, 4H), 3.08 (s, 3H). 13C NMR (CDCl3) δ 159.6, 158.6, 133.5, 132.6, 130.7, 128.98, 128.95, 128.3, 127.2, 125.1, 123.9, 120.3, 29.2. HRMS−ESI [M + Na]+ calcd for C13H10N2NaO2+, 249.0634, found 249.0625. 5-Methoxy-3-(naphthalen-2-yl)-1,2,4-oxadiazole (1n) and 4Methyl-3-(naphthalen-2-yl)-1,2,4-oxadiazol-5(4H)-one (2n). Title compounds were obtained according to the general procedure from oxadiazolone N. Compound 1n. White solid (520 mg, yield 46%). mp 88−89 °C. Rf = 0.45 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 8.57 (s, 1H), 8.10 (dd, J = 8.6, 1.5 Hz, 1H), 8.00−7.88 (m, 3H), 7.62−7.54 (m, 2H), 4.34 (s, 3H). 13C NMR (CDCl3) δ 174.1, 169.0, 134.7, 133.0, 128.8, 128.6, 127.9, 127.7, 127.5, 126.7, 124.5, 123.3, 60.3. HRMS−ESI [M + Na]+ calcd for C13H10N2NaO2+, 249.0634, found 249.0623. Compound 2n. White solid (531 mg, yield 47%). mp 142−144 °C. Rf = 0.08 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 8.17 (s, 1H), 8.05 (d, J = 8.5 Hz, 1H), 7.97 (t, J = 7.6 Hz, 2H), 7.71−7.62 (m, 3H), 3.43 (s, 3H). 13C NMR (CDCl3) δ 159.9, 158.8, 134.6, 132.7, 129.5, 129.0, 128.7, 128.5, 128.0, 127.5, 123.7, 120.5, 29.9. HRMS−ESI [M + Na]+ calcd for C13H10N2NaO2+, 249.0634, found 249.0643. 3-Benzyl-5-methoxy-1,2,4-oxadiazole (1o) and 3-Benzyl-4methyl-1,2,4-oxadiazol-5(4H)-one (2o).16b Title compounds were obtained according to the general procedure from oxadiazolone O. Compound 1o. Colorless oil (371 mg, yield 39%). 1H NMR (CDCl3) δ 7.43−7.26 (m, 5H), 4.15 (s, 3H), 3.96 (s, 2H). 13C NMR (CDCl3) δ 173.9, 170.5, 135.2, 128.9, 128.6, 127.0, 60.0, 33.0. HRMS−ESI [M + Na]+ calcd for C10H10N2NaO2+, 213.0634, found 213.0628. Compound 2o. White solid (504 mg, yield 53%). mp 106−108 °C. Rf = 0.07 (hexane−Et2O, 2:1). 1H NMR (CDCl3) δ 7.43−7.31 (m, 3H), 7.30−7.25 (m, 2H), 3.95 (s, 2H), 3.02 (s, 3H). 13C NMR (CDCl3) δ 159.5, 158.0, 131.6, 129.3, 128.4, 128.1, 31.1, 28.2. HRMS−ESI [M + Na]+ calcd for C10H10N2NaO2+, 213.0634, found 213.0638. 5-Methoxy-3-(3-methoxybenzyl)-1,2,4-oxadiazole (1p) and 3-(3Methoxybenzyl)-4-methyl-1,2,4-oxadiazol-5(4H)-one (2p). Title compounds were obtained according to the general procedure from oxadiazolone P. Compound 1p. Yellow oil (231 mg, yield 21%). Rf = 0.39 (hexane−Et2O, 1:1). 1H NMR (CDCl3) δ 7.28−7.24 (m, 1H), 6.94 (d, J = 7.6 Hz, 1H), 6.91−6.89 (m, 1H), 6.83 (dd, J = 8.2, 2.4 Hz, 1H), 4.17 (s, 3H), 3.92 (s, 2H), 3.82 (s, 3H). 13C NMR (CDCl3) δ 174.0, 170.4, 159.8, 136.7, 129.6, 121.3, 114.6, 112.6, 60.1, 55.2, 33.1. HRMS−ESI [M + Na]+ calcd for C11H12N2NaO3+, 243.0740, found 243.0732. Compound 2p. White solid (814 mg, yield 74%). mp 74−75 °C. Rf = 0.11 (hexane−Et2O, 1:1). 1H NMR (CDCl3) δ 7.35−7.27 (m, 1H), 6.92−6.82 (m, 2H), 6.82−6.77 (m, 1H), 3.92 (s, 2H), 3.82 (s, 3H), 3.03 (s, 3H). 13C NMR (CDCl3) δ 160.3, 159.5, 157.9, 133.1, 130.4, 120.7, 114.3, 113.3, 55.3, 31.2, 28.2. HRMS−ESI [M + Na]+ calcd for C11H12N2NaO3+, 243.0740, found 243.0749. Synthesis of 5-Benzyloxy-3-phenyl-1,2,4-oxadiazole (1q).36 To a suspension of NaH (1.7 mmol) in THF (7.5 mL) benzyl alcohol (2.2 mmol) was added and the mixture was stirred for 30 min. Then 5-chloro-3-phenyl-1,2,4-oxadiazole37 (0.85 mmol) was added and the reaction mixture was refluxed for 1 h and then cooled, quenched with water, and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by column chromatography on silica gel (eluent hexane− EtOAc, 5:1) afforded crude product (≈90% purity) which was used in further experiments. Colorless oil (83 mg, yield 40%). 1H NMR (CDCl3) δ 8.12−8.06 (m, 2H), 7.58−7.40 (m, 8H), 5.62 (s, 2H). HRMS−ESI [M + Na]+ calcd for C15H12N2NaO2+, 275.0791, found 275.0798. Synthesis of 5-(tert-Butoxy)-3-phenyl-1,2,4-oxadiazole (1r). A solution of 5-chloro-3-phenyl-1,2,4-oxadiazole37 (2 mmol) and tBuOK (2.4 mmol) in THF (7 mL) was refluxed for 1 h. Then the precipitate of KCl was filtered off and the solvent was removed in vacuo to yield the oxadiazole 1r as a white solid (332 mg, yield 76%). mp 29−30 °C. 1H NMR (CDCl3) δ 8.07−8.02 (m, 2H), 7.53−7.45 11238


Article

The Journal of Organic Chemistry (m, 3H), 1.72 (s, 9H). 13C NMR (CDCl3) δ 171.8, 168.8, 131.0, 128.6, 127.6, 127.0, 88.3, 27.6. HRMS−ESI [M + Na]+ calcd for C12H14N2NaO2+, 241.0947, found 241.0950. Synthesis of 1-(4-Methylphenylsulfonyl)-4-(4-nitrophenyl)1H-1,2,3-triazole (3f). Triazole 3f was prepared by reported procedure29 as a white solid (yield 52%). mp 191−193 °C (dec.). 1 H NMR (CDCl3) δ 8.49 (s, 1H), 8.33 (d, J = 8.9 Hz, 2H), 8.11− 8.03 (m, 4H), 7.44 (d, J = 8.2 Hz, 2H), 2.49 (s, 3H). 13C NMR (DMSO-d6) δ 147.2, 145.6, 144.3, 138.5, 137.6, 128.7, 128.1, 126.8, 126.0, 124.8, 21.3. HRMS−ESI [M + H]+ calcd for C15H13N4O4S+, 345.0652, found 345.0648. General Procedure for the Synthesis of Imidazole-1carboxylates 4. Oxadiazole 1 (0.2 mmol), triazole 3 (0.1 mmol), Rh2(Piv)4 (6 mg, 0.01 mmol), and DCE (0.5 mL) were placed into a screw cap glass tube and heated at 84 °C (oil bath temperature) under stirring until nitrogen evolution had ceased (about 2−5 min). Then triazole was added in 0.5 equiv portions (total amount see below) until full consumption of oxadiazole was detected (control by TLC, hexane−EtOAc 3:1). Each subsequent portion of triazole was added after the nitrogen evolution had stopped (about 2−5 min). The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent hexane− EtOAc, 3:1) to give imidazole 4. Imidazoles 4s,x, which were precipitated in the reaction mixture, were purified without using chromatography, namely, by filtration of the reaction mixture, washing of the product with Et2O−hexane mixture and drying under reduced pressure. Methyl 5-(4-methylphenylsulfonamido)-2,4-diphenyl-1H-imidazole-1-carboxylate (4a). This compound was obtained according to the general procedure from oxadiazole 1a and triazole 3a (0.6 mmol) as a white solid (81 mg, yield 91%). mp 196−197 °C (dec.). 1H NMR (DMSO-d6) δ 10.51 (s, 1H), 7.61−7.56 (m, 4H), 7.51−7.46 (m, 3H), 7.39 (d, J = 8.2 Hz, 2H), 7.20−7.13 (m, 3H), 7.09 (d, J = 8.2 Hz, 2H), 3.76 (s, 3H), 2.24 (s, 3H). 13C NMR (DMSO-d6) δ 149.7, 146.8, 143.6, 137.6, 137.5, 132.0, 130.7, 129.9, 129.8, 128.73, 128.72, 128.3, 127.7, 126.9, 126.8, 120.7, 55.5, 21.3. HRMS−ESI [M + H]+ calcd for C24H22N3O4S+, 448.1326, found 448.1315. Methyl 2-(4-methylphenyl)-5-(4-methylphenylsulfonamido)-4phenyl-1H-imidazole-1-carboxylate (4b). This compound was obtained according to the general procedure from oxadiazole 1b and triazole 3a (0.6 mmol) as a white solid (90 mg, yield 98%). mp 186−187 °C (dec.). 1H NMR (CDCl3) δ 7.76−7.69 (m, 2H), 7.51 (d, J = 8.2 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 7.22−7.15 (m, 3H), 7.02 (d, J = 8.2 Hz, 2H), 6.87 (s, 1H), 3.80 (s, 3H), 2.42 (s, 3H), 2.31 (s, 3H). 13C NMR (CDCl3) δ 149.9, 148.1, 144.1, 139.7, 138.4, 135.4, 131.4, 129.3, 128.72, 128.69, 127.90, 127.86, 127.7, 127.5, 127.0, 119.4, 54.7, 21.40, 21.39. HRMS−ESI [M + H]+ calcd for C25H24N3O4S+, 462.1482, found 462.1493. Methyl 2-(2-methylphenyl)-5-(4-methylphenylsulfonamido)-4phenyl-1H-imidazole-1-carboxylate (4c). This compound was obtained according to the general procedure from oxadiazole 1c and triazole 3a (0.6 mmol) as a white solid (89 mg, yield 96%). mp 87−89 °C (dec.). 1H NMR (CDCl3 δ 7.88−7.81 (m, 2H), 7.52 (d, J = 8.2 Hz, 2H), 7.39−7.33 (m, 1H), 7.30−7.20 (m, 6H), 7.10−7.03 (m, 3H), 3.62 (s, 3H), 2.32 (s, 3H), 2.24 (s, 3H). 13C NMR (CDCl3) δ 149.3, 147.5, 144.2, 138.4, 137.4, 135.4, 131.34, 131.29, 129.8, 129.6, 129.3 (2C), 127.9, 127.71, 127.68, 127.2, 125.4, 119.0, 54.5, 21.4, 19.6. HRMS−ESI [M + H]+ calcd for C25H24N3O4S+, 462.1482, found 462.1500. Methyl 2-(4-methoxyphenyl)-5-(4-methylphenylsulfonamido)-4phenyl-1H-imidazole-1-carboxylate (4d). This compound was obtained according to the general procedure from oxadiazole 1d and triazole 3a (0.6 mmol) as a white solid (93 mg, yield 97%). mp 192−193 °C (dec.). 1H NMR (DMSO-d6) δ 10.46 (s, 1H), 7.60− 7.50 (m, 4H), 7.38 (d, J = 8.1 Hz, 2H), 7.19−7.11 (m, 3H), 7.09 (d, J = 8.1 Hz, 2H), 7.03 (d, J = 8.8 Hz, 2H), 3.82 (s, 3H), 3.77 (s, 3H), 2.24 (s, 3H). 13C NMR (DMSO-d6) δ 160.6, 149.9, 146.8, 143.6, 137.7, 137.3, 132.1, 130.3, 129.8, 128.2, 127.6, 126.9, 126.8, 123.0, 120.3, 114.2, 55.7, 55.4, 21.3. HRMS−ESI [M + H]+ calcd for C25H24N3O5S+, 478.1431, found 478.1450.

Methyl 2-(4-fluorophenyl)-5-(4-methylphenylsulfonamido)-4phenyl-1H-imidazole-1-carboxylate (4e). This compound was obtained according to the general procedure from oxadiazole 1e and triazole 3a (0.5 mmol) as a white solid (79 mg, yield 85%). mp 186−187 °C (dec.). 1H NMR (CDCl3) δ 7.72−7.67 (m, 2H), 7.60− 7.54 (m, 2H), 7.53−7.49 (m, 2H), 7.22−7.11 (m, 5H), 7.03 (d, J = 8.1 Hz, 2H), 6.80 (br. s, 1H), 3.83 (s, 3H), 2.31 (s, 3H). 13C NMR (CDCl3) δ 163.5 (d, J = 250.0 Hz), 149.7, 147.0, 144.3, 138.6, 135.4, 131.2, 131.0 (d, J = 8.6 Hz), 129.3, 127.9, 127.7 (2C), 127.01, 126.95, 119.7, 115.2 (d, J = 22.0 Hz), 54.9, 21.4. HRMS−ESI [M + H]+ calcd for C24H21FN3O4S+, 466.1231, found 466.1227. Methyl 2-(3-fluorophenyl)-5-(4-methylphenylsulfonamido)-4phenyl-1H-imidazole-1-carboxylate (4f). This compound was obtained according to the general procedure from oxadiazole 1f and triazole 3a (0.6 mmol) as a white solid (91 mg, yield 98%). mp 161− 162 °C (dec.). 1H NMR (CDCl3) δ 7.73−7.67 (m, 2H), 7.51 (d, J = 8.2 Hz, 2H), 7.46−7.39 (m, 1H), 7.36−7.29 (m, 2H), 7.23−7.14 (m, 4H), 7.03 (d, J = 8.2 Hz, 2H), 6.84 (s, 1H), 3.83 (s, 3H), 2.31 (s, 3H). 13C NMR (CDCl3) δ 162.2 (d, J = 246.6 Hz), 149.6, 146.5 (d, J = 2.8 Hz), 144.3, 138.6, 135.4, 132.8 (d, J = 8.6 Hz), 131.2, 129.6 (d, J = 8.1 Hz), 129.3, 127.9, 127.7, 127.6, 127.0, 124.6 (d, J = 3.2 Hz), 119.9, 116.6 (d, J = 21.1 Hz), 116.1 (d, J = 23.5 Hz), 54.9, 21.4. HRMS−ESI [M + H]+ calcd for C24H21FN3O4S+, 466.1231, found 466.1234. Methyl 2-(4-chlorophenyl)-5-(4-methylphenylsulfonamido)-4phenyl-1H-imidazole-1-carboxylate (4g). This compound was obtained according to the general procedure from oxadiazole 1g and triazole 3a (0.6 mmol) as a white solid (94 mg, yield 98%). mp 177−178 °C (dec.). 1H NMR (CDCl3) δ 7.71−7.64 (m, 2H), 7.52 (d, J = 8.5 Hz, 2H), 7.47 (d, J = 8.2 Hz, 2H), 7.43 (d, J = 8.5 Hz, 2H), 7.22−7.14 (m, 3H), 7.01 (d, J = 8.2 Hz, 2H), 6.97 (br. s, 1H), 3.82 (s, 3H), 2.29 (s, 3H). 13C NMR (CDCl3) δ 149.6, 146.8, 144.2, 138.6, 135.8, 135.4, 131.2, 130.2, 129.3, 129.2, 128.3, 127.9, 127.7, 127.6, 127.0, 119.9, 54.9, 21.4. HRMS−ESI [M + H]+ calcd for C24H2135ClN3O4S+, 482.0936, found 482.0959. Methyl 2-(3-chlorophenyl)-5-(4-methylphenylsulfonamido)-4phenyl-1H-imidazole-1-carboxylate (4h). This compound was obtained according to the general procedure from oxadiazole 1h and triazole 3a (0.6 mmol) as a white solid (87 mg, yield 90%). mp 177−178 °C (dec.). 1H NMR (CDCl3 δ 7.74−7.67 (m, 2H), 7.62− 7.57 (m, 1H), 7.49 (d, J = 8.2 Hz, 2H), 7.47−7.41 (m, 2H), 7.41− 7.35 (m, 1H), 7.23−7.15 (m, 3H), 7.02 (d, J = 8.2 Hz, 2H), 6.95 (s, 1H), 3.82 (s, 3H), 2.31 (s, 3H). 13C NMR (CDCl3) δ 149.5, 146.4, 144.3, 138.7, 135.4, 134.0, 132.5, 131.1, 129.7, 129.3, 129.2, 129.1, 127.9, 127.72, 127.66, 127.01, 126.99, 120.0, 54.9, 21.4. HRMS−ESI [M + H]+ calcd for C24H2135ClN3O4S+, 482.0936, found 482.0956. Methyl 2-(4-bromophenyl)-5-(4-methylphenylsulfonamido)-4phenyl-1H-imidazole-1-carboxylate (4i). This compound was obtained according to the general procedure from oxadiazole 1i and triazole 3a (0.6 mmol) as a white solid (94 mg, yield 89%). mp 187− 188 °C (dec.). 1H NMR (CDCl3) δ 7.71−7.65 (m, 2H), 7.59 (d, J = 8.5 Hz, 2H), 7.52−7.42 (m, 4H), 7.22−7.14 (m, 3H), 7.01 (d, J = 8.1 Hz, 2H), 6.91 (s, 1H), 3.83 (s, 3H), 2.30 (s, 3H). 13C NMR (CDCl3) δ 149.6, 146.9, 144.3, 138.7, 135.4, 131.3, 131.2, 130.4, 129.7, 129.3, 127.9, 127.7, 127.6, 127.0, 124.1, 119.9, 54.9, 21.4. HRMS−ESI [M + H]+ calcd for C24H2179BrN3O4S+, 526.0431, found 526.0450. Methyl 5-(4-methylphenylsulfonamido)-4-phenyl-2-[4(trifluoromethyl)phenyl]-1H-imidazole-1-carboxylate (4j). This compound was obtained according to the general procedure from oxadiazole 1j and triazole 3a (0.6 mmol) as a white solid (89 mg, yield 86%). mp 148−149 °C (dec.). 1H NMR (CDCl3) δ 7.75−7.67 (m, 6H), 7.51 (d, J = 8.2 Hz, 2H), 7.23−7.15 (m, 3H), 7.03 (d, J = 8.2 Hz, 2H), 6.82 (s, 1H), 3.85 (s, 3H), 2.31 (s, 3H). 13C NMR (CDCl3) δ 149.5, 146.4, 144.4, 138.8, 135.4, 134.3, 131.4 (q, J = 32.7 Hz), 131.1, 129.4, 129.3, 128.0, 127.8, 127.6, 127.0, 125.0 (q, J = 3.6 Hz), 123.8 (q, J = 272.3 Hz), 120.2, 55.0, 21.4. HRMS−ESI [M + H]+ calcd for C25H21F3N3O4S+, 516.1199, found 516.1204. Methyl 5-(4-methylphenylsulfonamido)-4-phenyl-2-[3(trifluoromethyl)phenyl]-1H-imidazole-1-carboxylate (4k). This compound was obtained according to the general procedure from 11239


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(m, 2H), 7.50−7.44 (m, 4H), 7.44−7.38 (m, 1H), 7.38−7.29 (m, 5H), 7.22−7.16 (m, 3H), 7.08 (d, J = 6.9 Hz, 2H), 6.97 (d, J = 8.1 Hz, 2H), 5.14 (s, 2H), 2.23 (s, 3H) (NH signal is not observed). 13C NMR (CDCl3) δ 149.1, 147.8, 144.1, 138.3, 135.4, 133.1, 131.3, 130.8, 129.4, 129.2, 128.91, 128.88, 128.8, 128.5, 128.0, 127.8, 127.6, 127.5, 127.0, 119.9, 70.3, 21.3. HRMS−ESI [M + H]+ calcd for C30H26N3O4S+, 524.1639, found 524.1654. 2-(4-Bromophenyl)-N,N-dimethyl-5-(4-methylphenylsulfonamido)-4-phenyl-1H-imidazole-1-carboxamide (4s). This compound was obtained according to the general procedure (filtration and washing with Et2O instead of column chromatography) from oxadiazole 1s and triazole 3a (0.6 mmol) as a white solid (70 mg, yield 65%). mp 137−139 °C (dec.). 1H NMR (CDCl3) δ 7.64−7.58 (m, 4H), 7.55−7.48 (m, 4H), 7.17−7.07 (m, 3H), 6.98 (d, J = 8.1 Hz, 2H), 4.88 (br. s, 1H), 3.05 (s, 3H), 2.56 (s, 3H), 2.29 (s, 3H). 13C NMR (CDCl3) δ 150.8, 144.0, 143.2, 138.3, 136.2, 132.0, 131.8, 129.3, 129.0, 128.6, 127.9, 127.5, 127.1, 126.7, 124.1, 120.0, 38.5, 36.7, 21.4. HRMS−ESI [M + H]+ calcd for C25H2479BrN4O3S+, 539.0747, found 539.0765. Methyl 4-(4-methoxyphenyl)-5-(4-methylphenylsulfonamido)-2phenyl-1H-imidazole-1-carboxylate (4t). This compound was obtained according to the general procedure from oxadiazole 1a and triazole 3b (0.6 mmol) as a white solid (69 mg, yield 72%). mp 196−197 °C (dec.). 1H NMR (DMSO-d6) δ 10.42 (s, 1H), 7.60− 7.54 (m, 2H), 7.53−7.45 (m, 5H), 7.38 (d, J = 8.3 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 6.74−6.69 (m, 2H), 3.75 (s, 6H), 2.25 (s, 3H). 13C NMR (DMSO-d6) δ 159.1, 149.8, 146.7, 143.6, 137.9, 137.5, 130.8, 129.9, 129.8, 128.72, 128.70, 128.1, 126.9, 124.5, 119.7, 113.7, 55.5, 55.4, 21.3. HRMS−ESI [M + H]+ calcd for C25H24N3O5S+, 478.1431, found 478.1445. Methyl 4-(2-fluorophenyl)-5-(4-methylphenylsulfonamido)-2phenyl-1H-imidazole-1-carboxylate (4u). This compound was obtained according to the general procedure from oxadiazole 1a and triazole 3c (0.6 mmol) as a white solid (83 mg, yield 89%). mp 187−188 °C (dec.). 1H NMR (DMSO-d6) δ 10.43 (s, 1H), 7.60− 7.55 (m, 2H), 7.51−7.45 (m, 3H), 7.34−7.24 (m, 4H), 7.07−6.95 (m, 4H), 3.81 (s, 3H), 2.25 (s, 3H). 13C NMR (DMSO-d6) δ 159.4 (d, J = 249.5 Hz), 149.8, 147.0, 143.4, 137.2, 134.1 (d, J = 1.2 Hz), 131.2 (d, J = 3.0 Hz), 130.5, 130.1 (d, J = 8.2 Hz), 130.0, 129.6, 128.8, 128.6, 126.7, 124.2 (d, J = 3.0 Hz), 122.5, 120.1 (d, J = 14.0 Hz), 116.0 (d, J = 21.5 Hz), 55.6, 21.4. HRMS−ESI [M + H]+ calcd for C24H21FN3O4S+, 466.1231, found 466.1244. Methyl 4-(4-chlorophenyl)-5-(4-methylphenylsulfonamido)-2phenyl-1H-imidazole-1-carboxylate (4v). This compound was obtained according to the general procedure from oxadiazole 1a and triazole 3d (0.4 mmol) as a white solid (82 mg, yield 85%). mp 195−196 °C (dec.). 1H NMR (DMSO-d6) δ 10.57 (s, 1H), 7.63− 7.57 (m, 2H), 7.54 (d, J = 8.6 Hz, 2H), 7.51−7.45 (m, 3H), 7.36 (d, J = 8.2 Hz, 2H), 7.20 (d, J = 8.6 Hz, 2H), 7.10 (d, J = 8.2 Hz, 2H), 3.79 (s, 3H), 2.27 (s, 3H). 13C NMR (DMSO-d6) δ 149.7, 147.0, 143.9, 137.7, 136.4, 132.5, 130.9, 130.6, 130.0, 129.8, 128.8, 128.7, 128.4, 128.3, 126.9, 121.1, 55.6, 21.3. HRMS−ESI [M + H]+ calcd for C24H2135ClN3O4S+, 482.0936, found 482.0934. Methyl 5-(4-methylphenylsulfonamido)-2-phenyl-4-[4(trifluoromethyl)phenyl]-1H-imidazole-1-carboxylate (4w). This compound was obtained according to the general procedure from oxadiazole 1a and triazole 3e (0.6 mmol) as a white solid (82 mg, yield 80%). mp 198−199 °C (dec.). 1H NMR (DMSO-d6) δ 10.72 (s, 1H), 7.73 (d, J = 8.0 Hz, 2H), 7.64−7.58 (m, 2H), 7.54−7.44 (m, 5H), 7.35 (d, J = 8.0 Hz, 2H), 7.04 (d, J = 8.0 Hz, 2H), 3.82 (s, 3H), 2.18 (s, 3H). 13C NMR (DMSO-d6) δ 149.6, 146.9, 143.3, 137.6, 136.0, 135.4, 130.4, 129.9, 129.6, 128.7, 128.6, 127.6 (q, J = 31.7 Hz), 127.0, 126.8, 125.0 (q, J = 2.4 Hz), 124.6 (q, J = 271.8 Hz), 122.7, 55.5, 20.9. HRMS−ESI [M + H]+ calcd for C25H21F3N3O4S+, 516.1199, found 516.1195. Methyl 5-(4-methylphenylsulfonamido)-4-(4-nitrophenyl)-2phenyl-1H-imidazole-1-carboxylate (4x). This compound was obtained according to the general procedure (filtration and washing with Et2O instead of column chromatography) from oxadiazole 1a and triazole 3f (0.4 mmol) as a yellow solid (90 mg, yield 91%). mp

oxadiazole 1k and triazole 3a (0.6 mmol) as a white solid (93 mg, yield 90%). mp 177−178 °C (dec.). 1H NMR (DMSO-d6) δ 10.56 (s, 1H), 7.97 (s, 1H), 7.90 (d, J = 7.8 Hz, 1H), 7.87 (d, J = 7.8 Hz, 1H), 7.72 (t, J = 7.8 Hz, 1H), 7.63−7.57 (m, 2H), 7.39 (d, J = 8.1 Hz, 2H), 7.23−7.14 (m, 3H), 7.10 (d, J = 8.1 Hz, 2H), 3.75 (s, 3H), 2.25 (s, 3H). 13C NMR (DMSO-d6) δ 149.4, 145.5, 143.7, 137.9, 137.5, 133.2, 131.9, 131.8, 129.83, 129.81, 129.5 (q, J = 32.0 Hz), 128.3, 127.8, 126.9 (2C), 126.5 (q, J = 3.6 Hz), 125.7 (q, J = 3.8 Hz), 124.4 (q, J = 272.3 Hz), 121.1, 55.5, 21.3. HRMS−ESI [M + H]+ calcd for C25H21F3N3O4S+, 516.1199, found 516.1222. Methyl 5-(4-methylphenylsulfonamido)-2-(4-nitrophenyl)-4phenyl-1H-imidazole-1-carboxylate (4l). This compound was obtained according to the general procedure from oxadiazole 1l and triazole 3a (0.6 mmol) as a yellow solid (93 mg, yield 94%). mp 163− 165 °C (dec.). 1H NMR (CDCl3) δ 8.32 (d, J = 8.8 Hz, 2H), 7.79 (d, J = 8.8 Hz, 2H), 7.69−7.63 (m, 2H), 7.50 (d, J = 8.2 Hz, 2H), 7.23− 7.15 (m, 3H), 7.02 (d, J = 8.1 Hz, 2H), 6.86 (s, 1H), 3.90 (s, 3H), 2.31 (s, 3H). 13C NMR (CDCl3) δ 149.4, 148.3, 145.6, 144.5, 139.2, 136.8, 135.3, 130.8, 129.9, 129.4, 128.0, 127.9, 127.7, 127.0, 123.3, 120.7, 55.3, 21.4. HRMS−ESI [M + H]+ calcd for C24H21N4O6S+, 493.1176, found 493.1186. Methyl 5-(4-methylphenylsulfonamido)-2-(naphthalen-1-yl)-4phenyl-1H-imidazole-1-carboxylate (4m). This compound was obtained according to the general procedure from oxadiazole 1m and triazole 3a (0.4 mmol) as a white solid (93 mg, yield 93%); mp 193−194 °C (dec.). 1H NMR (CDCl3) δ 7.97 (d, J = 7.9 Hz, 1H), 7.94−7.87 (m, 3H), 7.63−7.48 (m, 7H), 7.28−7.21 (m, 3H), 7.09 (d, J = 8.1 Hz, 2H), 7.05 (s, 1H), 3.34 (s, 3H), 2.32 (s, 3H). 13C NMR (CDCl3) δ 149.4, 146.6, 144.3, 138.6, 135.5, 133.2, 132.1, 131.4, 130.0, 129.4, 129.1, 128.4, 128.0, 127.94, 127.79, 127.77, 127.2, 126.9, 126.1, 124.9, 124.6, 119.6, 54.4, 21.4. HRMS−ESI [M + H]+ calcd for C28H24N3O4S+, 498.1482, found 498.1476. Methyl 5-(4-methylphenylsulfonamido)-2-(naphthalen-2-yl)-4phenyl-1H-imidazole-1-carboxylate (4n). This compound was obtained according to the general procedure from oxadiazole 1n and triazole 3a (0.4 mmol) as a white solid (95 mg, yield 95%). mp 201−203 °C (dec.). 1H NMR (DMSO-d6) δ 10.58 (s, 1H), 8.21 (s, 1H), 8.13−8.06 (m, 1H), 8.05−7.96 (m, 2H), 7.70 (dd, J = 8.5, 1.6 Hz, 1H), 7.66−7.56 (m, 4H), 7.42 (d, J = 8.2 Hz, 2H), 7.23−7.14 (m, 3H), 7.10 (d, J = 8.2 Hz, 2H), 3.78 (s, 3H), 2.25 (s, 3H). 13C NMR (DMSO-d6) δ 149.8, 146.9, 143.6, 137.7, 137.6, 133.5, 132.8, 132.0, 129.8, 128.9, 128.33, 128.28, 128.2, 128.11, 128.06, 127.7, 127.6, 127.2, 126.9, 126.8, 126.0, 120.8, 55.5, 21.3. HRMS−ESI [M + H]+ calcd for C28H24N3O4S+, 498.1482, found 498.1502. Methyl 2-benzyl-5-(4-methylphenylsulfonamido)-4-phenyl-1Himidazole-1-carboxylate (4o). This compound was obtained according to the general procedure from oxadiazole 1o and triazole 3a (0.4 mmol) as a white solid (90 mg, yield 98%). mp 162−164 °C (dec.). 1H NMR (CDCl3) δ 7.82−7.79 (m, 2H), 7.41 (d, J = 8.2 Hz, 2H), 7.34−7.29 (m, 2H), 7.27−7.22 (m, 4H), 7.21−7.18 (m, 2H), 6.93 (d, J = 8.2 Hz, 2H), 6.76 (s, 1H), 4.35 (s, 2H), 3.73 (s, 3H), 2.28 (s, 3H). 13C NMR (CDCl3) δ 149.3, 148.3, 144.1, 138.0, 136.7, 135.2, 131.4, 129.2, 128.5, 128.3, 128.0, 127.7, 127.6, 127.1, 126.7, 119.1, 54.4, 36.4, 21.4; HRMS−ESI [M + H]+ calcd for C25H24N3O4S+ 462.1482, found 462.1490. Methyl 2-(3-methoxybenzyl)-5-(4-methylphenylsulfonamido)-4phenyl-1H-imidazole-1-carboxylate (4p). This compound was obtained according to the general procedure from oxadiazole 1p and triazole 3a (0.4 mmol) as a white solid (78 mg, yield 79%). mp 132−133 °C. 1H NMR (CDCl3) δ 7.82−7.75 (m, 2H), 7.41 (d, J = 8.2 Hz, 2H), 7.27−7.17 (m, 4H), 6.93 (d, J = 8.2 Hz, 2H), 6.86 (s, 1H), 6.82−6.72 (m, 3H), 4.32 (s, 2H), 3.79 (s, 3H), 3.73 (s, 3H), 2.27 (s, 3H). 13C NMR (CDCl3) δ 159.7, 149.3, 148.2, 144.1, 138.3, 138.0, 135.2, 131.4, 129.4, 129.2, 127.9, 127.7, 127.6, 127.1, 120.7, 119.1, 114.2, 111.9, 55.2, 54.4, 36.4, 21.3. HRMS−ESI [M + H]+ calcd for C26H26N3O5S+, 492.1588, found 492.1610. Benzyl 5-(4-methylphenylsulfonamido)-2,4-diphenyl-1H-imidazole-1-carboxylate (4q). This compound was obtained according to the general procedure from oxadiazole 1q and triazole 3a (0.6 mmol) as a colorless oil (96 mg, yield 92%). 1H NMR (CDCl3) δ 7.76−7.71 11240


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The Journal of Organic Chemistry 204−206 °C (dec.). 1H NMR (CDCl3) δ 8.08−8.03 (m, 2H), 8.02− 7.98 (m, 2H), 7.57−7.45 (m, 7H), 7.13−7.06 (m, 3H), 3.76 (s, 3H), 2.30 (s, 3H). 13C NMR (CDCl3) δ 149.6, 148.3, 146.8, 145.0, 137.9, 135.8, 135.5, 130.3, 130.0, 129.5, 128.7, 128.2, 127.7, 127.5, 123.2, 122.0, 55.0, 21.3. HRMS−ESI [M + H]+ calcd for C24H21N4O6S+, 493.1176, found 493.1197. Methyl 5-(methylsulfonamido)-2,4-diphenyl-1H-imidazole-1carboxylate (4y). This compound was obtained according to the general procedure from oxadiazole 1a and triazole 3g (0.8 mmol) as a white solid (56 mg, yield 75%). mp 86−88 °C (dec.). 1H NMR (CDCl3) δ 8.02 (d, J = 7.3 Hz, 2H), 7.65−7.59 (m, 2H), 7.51−7.45 (m, 5H), 7.38 (t, J = 7.4 Hz, 1H), 6.63 (s, 1H), 3.92 (s, 3H), 2.72 (s, 3H). 13C NMR (CDCl3) δ 149.9, 148.6, 138.4, 131.5, 130.8, 129.7, 128.8, 128.7, 128.6, 128.1, 127.4, 119.6, 55.0, 41.0. HRMS−ESI [M + H]+ calcd for C18H18N3O4S+, 372.1013, found 372.1025. Methyl 2,4-diphenyl-5-(2,4,6-trimethylphenylsulfonamido)-1Himidazole-1-carboxylate (4z). This compound was obtained according to the general procedure from oxadiazole 1a and triazole 3h (0.4 mmol) as a colorless oil (81 mg, yield 85%).; 1H NMR (CDCl3) δ 7.61−7.55 (m, 4H), 7.49−7.43 (m, 3H), 7.17−7.10 (m, 3H), 6.85 (s, 1H), 6.62 (s, 2H), 3.86 (s, 3H), 2.39 (s, 6H), 2.15 (s, 3H). 13C NMR (CDCl3) δ 149.9, 148.0, 143.0, 140.0, 139.2, 132.0, 131.7, 131.2, 130.9, 129.6, 128.8, 128.0, 127.6, 127.4, 127.0, 119.9, 54.8, 22.9, 20.8. HRMS−ESI [M + H]+ calcd for C26H26N3O4S+, 476.1639, found 476.1644. Methyl 5-(4-methoxyphenylsulfonamido)-2,4-diphenyl-1H-imidazole-1-carboxylate (4za). This compound was obtained according to the general procedure from oxadiazole 1a and triazole 3i (0.4 mmol) as a white solid (85 mg, yield 92%). mp 177−178 °C (dec.). 1 H NMR (CDCl3) δ 7.76−7.71 (m, 2H), 7.60−7.53 (m, 4H), 7.49− 7.42 (m, 3H), 7.24−7.16 (m, 3H), 6.85 (s, 1H), 6.68 (d, J = 8.9 Hz, 2H), 3.82 (s, 3H), 3.78 (s, 3H). 13C NMR (CDCl3) δ 163.4, 149.9, 147.9, 138.4, 131.5, 130.9, 129.9, 129.8, 129.6, 128.8, 128.0, 127.9, 127.7, 127.1, 119.8, 113.9, 55.5, 54.8. HRMS−ESI [M + Na]+ calcd for C24H21N3NaO5S+, 486.1094, found 486.1085. General Procedure for the Synthesis of N-Alkylimidazoles 5. Oxadiazol-5(4H)-one 2 (0.2 mmol), triazole 3 (0.24 mmol), Rh2(Piv)4 (6 mg, 0.01 mmol), and DCE (0.5 mL) were placed into a screw cap glass tube and heated at 84 °C (oil bath temperature) under stirring until nitrogen evolution had ceased (about 2−5 min). The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent hexane− EtOAc, 3:1) to give imidazole 5. Imidazoles 5d−g,i,p, which were precipitated in the reaction mixture, were purified without using chromatography, namely, by filtration of the reaction mixture, washing of the product with Et2O−hexane mixture and drying under reduced pressure. 4-Methyl-N-(1-methyl-2,4-diphenyl-1H-imidazol-5-yl)benzenesulfonamide (5a). This compound was obtained according to the general procedure from oxadiazolone 2a and triazole 3a as a white solid (69 mg, yield 85%). mp 196−197 °C. 1H NMR (DMSOd6) δ 10.27 (s, 1H), 7.75−7.70 (m, 2H), 7.55−7.45 (m, 5H), 7.42 (d, J = 8.3 Hz, 2H), 7.11−7.03 (m, 5H), 3.53 (s, 3H), 2.24 (s, 3H). 13C NMR (DMSO-d6) δ 145.6, 143.7, 137.7, 136.0, 133.6, 131.0, 129.8, 129.3, 129.1, 128.8, 128.0, 127.0, 126.4, 126.3, 122.0, 32.0, 21.4. HRMS−ESI [M + H]+ calcd for C23H22N3O2S+, 404.1427, found 404.1427. 4-Methyl-N-[1-methyl-2-(4-methylphenyl)-4-phenyl-1H-imidazol-5-yl]benzenesulfonamide (5b). This compound was obtained according to the general procedure from oxadiazolone 2b and triazole 3a as a white solid (68 mg, yield 81%). mp 199−200 °C. 1H NMR (CDCl3) δ 7.59 (d, J = 7.9 Hz, 2H), 7.33−7.28 (m, 2H), 7.27−7.19 (m, 4H), 7.08−6.95 (m, 3H), 6.80 (d, J = 7.9 Hz, 2H), 3.54 (s, 3H), 2.42 (s, 3H), 2.21 (s, 3H) (NH signal is not observed). 13C NMR (CDCl3) δ 146.6, 143.7, 139.1, 136.5, 135.5, 132.7, 129.2, 129.1, 128.8, 127.8, 127.5, 127.2, 126.5, 126.3, 120.7, 32.0, 21.3 (2C). HRMS−ESI [M + H]+ calcd for C24H24N3O2S+, 418.1584, found 418.1600. 4-Methyl-N-[1-methyl-2-(2-methylphenyl)-4-phenyl-1H-imidazol-5-yl]benzenesulfonamide (5c). This compound was obtained

according to the general procedure from oxadiazolone 2c and triazole 3a as a white solid (74 mg, yield 89%). mp 198−200 °C. 1H NMR (CDCl3) δ 7.43−7.30 (m, 6H), 7.29−7.24 (m, 2H), 7.11−7.01 (m, 3H), 6.93−6.85 (m, 3H), 3.47 (s, 3H), 2.30 (s, 3H), 2.24 (s, 3H). 13C NMR (CDCl3) δ 146.5, 143.7, 138.3, 136.4, 135.2, 132.8, 130.41, 130.38, 130.3, 129.6, 129.1, 127.7, 127.2, 126.5, 126.2, 125.8, 120.0, 30.9, 21.3, 19.6. HRMS−ESI [M + H]+ calcd for C24H24N3O2S+, 418.1584, found 418.1586. N-(2-(4-Methoxyphenyl)-1-methyl-4-phenyl-1H-imidazol-5-yl)4-methylbenzenesulfonamide (5d). This compound was obtained according to the general procedure (filtration and washing with Et2O instead of column chromatography) from oxadiazolone 2d and triazole 3a as a white solid (79 mg, yield 91%). mp 201−203 °C. 1H NMR (CDCl3) δ 7.62 (d, J = 8.7 Hz, 2H), 7.25−7.21 (m, 4H), 7.07− 6.94 (m, 5H), 6.79 (d, J = 8.1 Hz, 2H), 3.86 (s, 3H), 3.49 (s, 3H), 2.20 (s, 3H) (NH signal is not observed). 13C NMR (CDCl3) δ 160.2, 146.4, 143.6, 136.4, 135.6, 132.8, 130.3, 129.1, 127.7, 127.1, 126.5, 126.2, 122.9, 120.6, 114.0, 55.3, 31.9, 21.3. HRMS−ESI [M + H]+ calcd for C24H24N3O3S+, 434.1533, found 434.1543. N-[2-(4-Chlorophenyl)-1-methyl-4-phenyl-1H-imidazol-5-yl]-4methylbenzenesulfonamide (5e). This compound was obtained according to the general procedure (filtration and washing with Et2O instead of column chromatography) from oxadiazolone 2g and triazole 3a as a white solid (83 mg, yield 95%). Gram-scale synthesis of 5e: Oxadiazol-5(4H)-one 2g (632 mg, 3.0 mmol), triazole 3a (1076 mg, 3.6 mmol), Rh2(Piv)4 (18 mg, 0.03 mmol), and DCE (6 mL) were placed into round-bottom flask and refluxed under stirring until nitrogen evolution had ceased (about 5 min). The reaction mixture was cooled to ambient temperature and diluted with Et2O. The resulting precipitate was filtered off, washed with Et2O and dried under reduced pressure. Yield of imidazole 5e: 1.11 g (84%). mp 199−201 °C. 1H NMR (CDCl3) δ 7.66 (d, J = 8.3 Hz, 2H), 7.49 (d, J = 8.3 Hz, 2H), 7.38 (br. s, 1H), 7.28−7.23 (m, 2H), 7.20 (d, J = 7.2 Hz, 2H), 7.10−6.96 (m, 3H), 6.83 (d, J = 8.0 Hz, 2H), 3.58 (s, 3H), 2.22 (s, 3H). 13C NMR (CDCl3) δ 145.5, 143.9, 136.9, 135.4, 135.3, 132.6, 130.1, 129.2, 128.92, 128.87, 127.8, 127.2, 126.5, 126.4, 121.1, 32.1, 21.4. HRMS−ESI [M + H]+ calcd for C23H2135ClN3O2S+, 438.1038, found 438.1051. 4-Methyl-N-[1-methyl-4-phenyl-2-(4-(trifluoromethyl)phenyl]1H-imidazol-5-yl)benzenesulfonamide (5f). This compound was obtained according to the general procedure (filtration and washing with Et2O instead of column chromatography) from oxadiazolone 2j and triazole 3a as a white solid (89 mg, yield 94%). mp 210−211 °C. 1 H NMR (CDCl3) δ 7.89 (d, J = 8.2 Hz, 2H), 7.78 (d, J = 8.2 Hz, 2H), 7.38 (d, J = 8.2 Hz, 2H), 7.26−7.20 (m, 2H), 7.14−7.04 (m, 3H), 6.90 (d, J = 8.2 Hz, 2H), 6.73 (br. s, 1H), 3.80 (s, 3H), 2.25 (s, 3H). 13C NMR (CDCl3) δ 145.2, 144.2, 137.3, 135.1, 133.9, 132.5, 131.0 (q, J = 32.9 Hz), 129.3, 129.1, 127.9, 127.2, 126.7, 126.4, 125.6 (q, J = 3.5 Hz), 123.9 (q, J = 272.3 Hz), 121.5, 32.4, 21.4. HRMS− ESI [M + H]+ calcd for C24H21F3N3O2S+, 472.1301, found 472.1316. 4-Methyl-N-[1-methyl-2-(4-nitrophenyl)-4-phenyl-1H-imidazol5-yl]benzenesulfonamide (5g). This compound was obtained according to the general procedure (filtration and washing with Et2O instead of column chromatography) from oxadiazolone 2l and triazole 3a as a yellow solid (83 mg, yield 93%). mp 259−260 °C; 1H NMR (CDCl3) δ 8.38 (d, J = 8.9 Hz, 2H), 7.98 (d, J = 8.9 Hz, 2H), 7.41 (d, J = 8.2 Hz, 2H), 7.25−7.21 (m, 2H), 7.16−7.07 (m, 3H), 6.92 (d, J = 8.2 Hz, 2H), 6.63 (br. s, 1H), 3.88 (s, 3H), 2.27 (s, 3H). 13 C NMR (CDCl3) δ 147.5, 143.8, 143.4, 137.5, 136.9 (2C), 133.2, 129.8, 129.6, 128.1, 127.0, 126.8, 126.4, 124.3, 123.5, 32.4, 21.4. HRMS−ESI [M + H]+ calcd for C23H21N4O4S+, 449.1278, found 449.1291. 4-Methyl-N-[1-methyl-2-(naphthalen-1-yl)-4-phenyl-1H-imidazol-5-yl]benzenesulfonamide (5h). This compound was obtained according to the general procedure from oxadiazolone 2m and triazole 3a as a colorless oil (84 mg, yield 93%). 1H NMR (CDCl3) δ 8.01 (d, J = 8.2 Hz, 1H), 7.98−7.95 (m, 1H), 7.78−7.73 (m, 1H), 7.69−7.65 (m, 1H), 7.64−7.53 (m, 4H), 7.35−7.28 (m, 4H), 7.04 (t, J = 7.3 Hz, 1H), 6.96 (t, J = 7.4 Hz, 2H), 6.83 (d, J = 8.0 Hz, 2H), 3.30 (s, 3H), 2.22 (s, 3H). 13C NMR (CDCl3) δ 145.7, 143.8, 136.8, 135.4, 133.6, 11241


Article

The Journal of Organic Chemistry 132.8, 132.2, 130.0, 129.1, 129.0, 128.4, 128.0, 127.8, 127.3, 127.2, 126.5, 126.3 (2C), 125.4, 125.1, 120.5, 31.4, 21.3. HRMS−ESI [M + H]+ calcd for C27H24N3O2S+, 454.1584, found 454.1599. 4-Methyl-N-[1-methyl-2-(naphthalen-2-yl)-4-phenyl-1H-imidazol-5-yl]benzenesulfonamide (5i). This compound was obtained according to the general procedure (filtration and washing with Et2O instead of column chromatography) from oxadiazolone 2n and triazole 3a as a white solid (88 mg, yield 97%). mp 237−239 °C; 1H NMR (DMSO-d6) δ 10.33 (s, 1H), 8.30 (s, 1H), 8.11−8.02 (m, 2H), 8.01−7.96 (m, 1H), 7.91 (dd, J = 8.5, 1.5 Hz, 1H), 7.62−7.53 (m, 4H), 7.45 (d, J = 8.2 Hz, 2H), 7.12−7.05 (m, 5H), 3.66 (s, 3H), 2.24 (s, 3H). 13C NMR (DMSO-d6) δ 145.5, 143.7, 137.7, 136.2, 133.6, 133.1, 129.8, 128.9, 128.6, 128.4, 128.1 (2C), 127.8, 127.3 (2C), 127.1, 127.0, 126.5, 126.4, 126.3, 122.3, 32.3, 21.4. HRMS−ESI [M + H]+ calcd for C27H24N3O2S+, 454.1584, found 454.1598. N-(2-Benzyl-1-methyl-4-phenyl-1H-imidazol-5-yl)-4-methylbenzenesulfonamide (5j). This compound was obtained according to the general procedure from oxadiazolone 2o and triazole 3a as a colorless oil (73 mg, yield 87%). 1H NMR (CDCl3) δ 7.36−7.24 (m, 6H), 7.24−7.18 (m, 4H), 7.07−6.96 (m, 3H), 6.83 (d, J = 8.1 Hz, 2H), 4.15 (s, 2H), 3.36 (s, 3H), 2.22 (s, 3H). 13C NMR (CDCl3) δ 145.8, 143.9, 136.4, 136.1, 135.1, 132.9, 129.1, 128.8, 128.2, 127.8, 127.2, 126.8, 126.4, 126.3, 119.7, 34.5, 30.2, 21.3. HRMS−ESI [M + H]+ calcd for C24H24N3O2S+, 418.1584, found 418.1568. N-(2-(3-Methoxybenzyl)-1-methyl-4-phenyl-1H-imidazol-5-yl)-4methylbenzenesulfonamide (5k). This compound was obtained according to the general procedure from oxadiazolone 2p and triazole 3a as a colorless oil (72 mg, yield 80%). 1H NMR (CDCl3) δ 7.31− 7.18 (m, 6H), 7.04−6.98 (m, 1H), 6.95 (t, J = 7.4 Hz, 2H), 6.84− 6.72 (m, 5H), 4.11 (s, 2H), 3.80 (s, 3H), 3.29 (s, 3H), 2.20 (s, 3H). 13 C NMR (CDCl3) δ 159.9, 145.5, 143.7, 138.0, 136.0, 135.2, 132.8, 129.7, 129.0, 127.7, 127.1, 126.4, 126.2, 120.5, 119.9, 113.9, 112.1, 55.2, 34.3, 30.2, 21.3. HRMS−ESI [M + H]+ calcd for C25H26N3O3S+, 448.1689, found 448.1703. N-(1-Benzyl-2,4-diphenyl-1H-imidazol-5-yl)-4-methylbenzenesulfonamide (5l). This compound was obtained according to the general procedure from oxadiazolone 2q and triazole 3a as a white solid (90 mg, yield 94%). mp 221−223 °C. 1H NMR (DMSO-d6) δ 10.35 (s, 1H), 7.60−7.55 (m, 2H), 7.51−7.47 (m, 2H), 7.45−7.40 (m, 3H), 7.38 (d, J = 8.2 Hz, 2H), 7.30 (t, J = 7.3 Hz, 2H), 7.26−7.20 (m, 1H), 7.10−6.98 (m, 5H), 6.94 (d, J = 7.3 Hz, 2H), 5.40 (br. s, 2H), 2.20 (s, 3H). 13C NMR (DMSO-d6) δ 146.0, 143.6, 137.7, 137.5, 136.4, 133.4, 131.1, 129.7, 129.4, 129.1, 129.0, 128.7, 128.0, 127.7, 127.0, 126.5, 126.4, 126.3, 121.8, 46.9, 21.3. HRMS−ESI [M + H]+ calcd for C29H26N3O2S+, 480.1740, found 480.1745. N-[4-(4-Methoxyphenyl)-1-methyl-2-phenyl-1H-imidazol-5-yl]4-methylbenzenesulfonamide (5m). This compound was obtained according to the general procedure from oxadiazolone 2a and triazole 3b as a white solid (64 mg, yield 74%). mp 182−184 °C. 1H NMR (CDCl3) δ 7.72−7.67 (m, 2H), 7.53−7.42 (m, 3H), 7.29 (d, J = 8.1 Hz, 2H), 7.17 (d, J = 8.7 Hz, 2H), 6.85 (d, J = 8.1 Hz, 2H), 6.54 (d, J = 8.7 Hz, 2H), 3.74 (s, 3H), 3.53 (s, 3H), 2.24 (s, 3H) (NH signal is not observed). 13C NMR (CDCl3) δ 158.4, 146.3, 143.7, 136.7, 136.0, 130.6, 129.1, 129.0, 128.9, 128.6, 127.7, 127.2, 125.7, 120.3, 113.2, 55.1, 31.9, 21.3. HRMS−ESI [M + H]+ calcd for C24H24N3O3S+, 434.1533, found 434.1553. N-[4-(2-Fluorophenyl)-1-methyl-2-phenyl-1H-imidazol-5-yl]-4methylbenzenesulfonamide (5n). This compound was obtained according to the general procedure from oxadiazolone 2a and triazole 3c as a white solid (76 mg, yield 90%). mp 141−143 °C. 1H NMR (CDCl3) δ 7.76−7.70 (m, 2H), 7.54−7.44 (m, 3H), 7.43−7.37 (m, 1H), 7.35 (d, J = 8.2 Hz, 2H), 7.14−7.06 (m, 1H), 6.98 (t, J = 7.4 Hz, 1H), 6.84−6.74 (m, 3H), 3.85 (s, 3H), 2.18 (s, 3H) (NH signal is not observed). 13C NMR (CDCl3) δ 158.6 (d, J = 242.2 Hz), 147.5, 143.9, 134.5, 130.8, 130.7 (d, J = 4.2 Hz), 130.4, 129.2, 129.1, 128.8, 128.6, 128.1 (d, J = 8.9 Hz), 127.0, 124.0 (d, J = 2.7 Hz), 122.9, 120.7 (d, J = 13.9 Hz), 115.1 (d, J = 23.6 Hz), 32.6, 21.3. HRMS−ESI [M + H]+ calcd for C23H21FN3O2S+, 422.1333, found 422.1350. N-[4-(4-Chlorophenyl)-1-methyl-2-phenyl-1H-imidazol-5-yl]-4methylbenzenesulfonamide (5o). This compound was obtained

according to the general procedure from oxadiazolone 2a and triazole 3d as a white solid (80 mg, yield 91%). mp 224−225 °C. 1H NMR (CDCl3) δ 7.72−7.66 (m, 2H), 7.65−7.31 (m, 4H), 7.27 (d, J = 8.1 Hz, 2H), 7.16 (d, J = 8.5 Hz, 2H), 6.95 (d, J = 8.5 Hz, 2H), 6.88 (d, J = 8.1 Hz, 2H), 3.56 (s, 3H), 2.30 (s, 3H). 13C NMR (CDCl3) δ 146.9, 144.4, 135.84, 135.78, 132.3, 131.4, 130.3, 129.3, 129.2, 128.9, 128.7, 127.9, 127.7, 127.2, 121.0, 31.9, 21.4. HRMS−ESI [M + H]+ calcd for C23H2135ClN3O2S+, 438.1038, found 438.1056. 4-Methyl-N-[1-methyl-4-(4-nitrophenyl)-2-phenyl-1H-imidazol5-yl]benzenesulfonamide (5p). This compound was obtained according to the general procedure (filtration and washing with Et2O instead of column chromatography) from oxadiazolone 2a and triazole 3f as a yellow solid (84 mg, yield 94%). mp 221−223 °C. 1H NMR (DMSO-d6) δ 10.55 (br. s, 1H), 7.91 (d, J = 8.8 Hz, 2H), 7.79−7.73 (m, 2H), 7.71 (d, J = 8.8 Hz, 2H), 7.58−7.48 (m, 3H), 7.41 (d, J = 8.1 Hz, 2H), 7.06 (d, J = 8.1 Hz, 2H), 3.62 (s, 3H), 2.13 (s, 3H). 13C NMR (DMSO-d6) δ 146.6, 145.5, 144.1, 140.3, 137.5, 133.7, 130.5, 129.8, 129.7, 129.1, 128.9, 127.1, 126.7, 124.4, 123.5, 32.2, 21.1; HRMS−ESI [M + H]+ calcd for C23H21N4O4S+, 449.1278, found 449.1288. N-(1-Methyl-2,4-diphenyl-1H-imidazol-5-yl)methanesulfonamide (5q). This compound was obtained according to the general procedure from oxadiazolone 2a and triazole 3g as a white solid (62 mg, yield 95%). mp 224−226 °C. 1H NMR (CDCl3) δ 7.79−7.73 (m, 2H), 7.70−7.63 (m, 2H), 7.53−7.43 (m, 3H), 7.32− 7.23 (m, 3H), 3.33 (s, 3H), 2.43 (s, 3H) (NH signal is not observed). 13 C NMR (CDCl3) δ 146.7, 136.7, 133.0, 130.3, 129.3, 129.0, 128.61, 128.60, 127.6, 127.3, 121.1, 40.6, 31.4. HRMS−ESI [M + H]+ calcd for C17H18N3O2S+, 328.1114, found 328.1124. 2,4,6-Trimethyl-N-(1-methyl-2,4-diphenyl-1H-imidazol-5-yl)benzenesulfonamide (5r). This compound was obtained according to the general procedure from oxadiazolone 2a and triazole 3h as a colorless oil (80 mg, yield 93%). 1H NMR (CDCl3) δ 7.72−7.66 (m, 2H), 7.53−7.43 (m, 3H), 7.26−7.20 (m, 2H), 7.13−7.05 (m, 3H), 6.88 (br. s, 1H), 6.54 (s, 2H), 3.75 (s, 3H), 2.29 (s, 6H), 2.13 (s, 3H). 13 C NMR (CDCl3) δ 146.9, 142.7, 139.2, 138.0, 132.6, 132.4, 131.8, 130.6, 129.1, 128.9, 128.6, 127.7, 126.7, 126.6, 120.5, 32.3, 23.1, 20.8. HRMS−ESI [M + H]+ calcd for C25H26N3O2S+, 432.1740, found 432.1758. 4-Methoxy-N-(1-methyl-2,4-diphenyl-1H-imidazol-5-yl)benzenesulfonamide (5s). This compound was obtained according to the general procedure from oxadiazolone 2a and triazole 3i as a white solid (79 mg, yield 94%). mp 184−186 °C. 1H NMR (CDCl3) δ 7.76−7.70 (m, 2H), 7.54−7.44 (m, 3H), 7.36 (d, J = 8.8 Hz, 2H), 7.29−7.23 (m, 2H), 7.10−7.04 (m, 3H), 7.01 (br. s, 1H), 6.52 (d, J = 8.8 Hz, 2H), 3.74 (s, 3H), 3.69 (s, 3H). 13C NMR (CDCl3) δ 162.9, 146.5, 136.6, 132.9, 130.5, 130.1, 129.2, 129.0, 128.9, 128.6, 127.8, 126.5, 126.4, 121.1, 113.6, 55.3, 31.9. HRMS−ESI [M + H]+ calcd for C23H22N3O3S+, 420.1376, found 420.1391. Synthesis of N-[2-(4-Chlorophenyl)-4-phenyl-1H-imidazol5-yl]-N,4-dimethylbenzenesulfonamide (12). Compound 4g (0.2 mmol) was placed in a round-bottom flask and heated at 190 °C for 10 min. The reaction mixture was purified by column chromatography on silica gel (eluent CHCl3) to give compound 12 as a white solid (59 mg, yield 67%). mp 229−231 °C; 1H NMR (DMSO-d6) δ 12.72 (br. s, 1H), 7.94−7.88 (m, 4H), 7.75 (d, J = 8.2 Hz, 2H), 7.55 (d, J = 8.6 Hz, 2H), 7.50 (t, J = 7.7 Hz, 2H), 7.43 (d, J = 8.2 Hz, 2H), 7.39−7.33 (m, 1H), 3.03 (s, 3H), 2.44 (s, 3H); 13C NMR (DMSO-d6) δ 143.9, 142.6, 136.6, 135.2, 133.6, 129.7, 129.4, 129.3 (2C), 129.03, 128.95, 128.0, 127.8, 127.4, 126.6, 38.4, 21.5; HRMS−ESI [M + Na]+ calcd for C23H2035ClN3NaO2S+ 460.0857, found 460.0848.

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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b01809. 11242


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Full optimization conditions for the synthesis of 4a, Xray structures for compounds 4e, 5a, and 1H, 13C NMR spectra (PDF) Crystal data (CIF) Crystal data (CIF)

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Nikolai V. Rostovskii: 0000-0002-8925-794X Alexander F. Khlebnikov: 0000-0002-6100-0309 Mikhail S. Novikov: 0000-0001-5106-4723 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We gratefully acknowledge the financial support of the Russian Foundation for Basic Research (Grant No. 18-33-00423, 1603-00596) and Saint Petersburg State University (Grant No. 12.40.1427.2017). This research used resources of Magnetic Resonance Research Centre, Chemical Analysis and Materials Research Centre, Centre for X-ray Diffraction Studies, and Chemistry Educational Centre of the Research Park of St. Petersburg State University.

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REFERENCES

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