Rh(II)-Catalyzed Transannulation of 1,2,4-Oxadiazole Derivatives with 1-Sulfonyl-1,2,3-triazoles: Regioselective Synthesis of 5-Sulfonamidoimidazoles

Article abstract of DOI:10.1021/acs.joc.8b01809

An effective method for the synthesis of fully substituted 5-sulfonamidoimidazoles by Rh(II)-catalyzed transannulation of 1,2,4-oxadiazole derivatives with N-sulfonyl-1,2,3-triazoles is reported. The reaction works well with both aromatic 1,2,4-oxadiazoles and 1,2,4-oxadiazol-5-ones 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.

Full text of DOI:10.1021/acs.joc.8b01809

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Article
Rh(II)-Catalyzed Transannulation of 1,2,4-Oxadiazole Derivatives with 1-
Sulfonyl-1,2,3-triazoles: Regioselective Synthesis of 5-Sulfonamidoimidazoles
Julia O. Ruvinskaya, Nikolai V. Rostovskii, Galina L. Starova,
Alexander F. Khlebnikov, and Mikhail Sergeevich Novikov
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01809 • Publication Date (Web): 30 Jul 2018
Downloaded from http://pubs.acs.org on July 30, 2018
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Rh(II)ꢀCatalyzed Transannulation of 1,2,4ꢀOxadiazole Derivatives with
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1ꢀSulfonylꢀ1,2,3ꢀtriazoles: Regioselective Synthesis of 5ꢀSulfonamidoimidazoles
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Julia O. Ruvinskaya, Nikolai V. Rostovskii, Galina L. Starova, Alexander F. Khlebnikov, Mikhail S.
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Novikov*
St. Petersburg State University, Institute of Chemistry, 7/9 Universitetskaya nab., St. Petersburg,
199034 Russia
Graphical abstract
ABSTRACT: An effective method for the synthesis of fully substituted 5ꢀsulfonamidoimidazoles by
Rh(II)ꢀcatalyzed transannulation of 1,2,4ꢀoxadiazole derivatives with Nꢀsulfonylꢀ1,2,3ꢀtriazoles is
reported. The reaction works well with both aromatic 1,2,4ꢀoxadiazoles and 1,2,4ꢀoxadiazolꢀ5ꢀones
providing a flexible approach to Nꢀ(alkoxy/amino)carbonylꢀ and Nꢀalkylꢀsubstituted imidazoles.
Both the disclosed reactions are completely regioselective and provide the first examples of a carbeꢀ
noidꢀmediated transformation of N,N,Oꢀheterocycles.
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
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5ꢀamino, 5ꢀacylamino and 5ꢀsulfonamido derivatives deserve special attention.3 Thus, 5ꢀ
aminoimidazole ribonucleotide (AIR) is a key intermediate in the biosynthesis of the purine ribonuꢀ
cleotides4 and thiamin (vitamin B1).5 The core of 5ꢀaminoimidazole is presented in the structure of
some bioactive compounds exhibiting antifungal, antiplatelet and adenosine A2A receptor antagonist
activities (Scheme 1).6 5ꢀAminoimidazoleꢀ4ꢀcarboxamides were also shown to be promising for
treating diseases mediated by a heat shock protein 90 (Hsp 90).7
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Scheme 1. Bioactive 5ꢀAminoimidazole Derivatives
Of the numerous methods used for the synthesis of triꢀ and tetraꢀsubstituted 1Hꢀimidazoles,8 onꢀ
ly a few can be employed for the preparation of 5ꢀaminoimidazoles.6a, 9–11 The limited scope of subꢀ
stituents that can be introduced into the imidazole ring and the poor availability of the starting mateꢀ
rials motivated us to search for new approaches to these compounds. In the last few years, several
impressive examples of the synthesis of pyridines12 and isoquinolines13 via the transannulation of
1,2,4ꢀoxadiazole derivatives were reported. The synthetic availability of diversely substituted 1,2,4ꢀ
oxadiazoles14 and their 5ꢀoxo 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 1,2,4ꢀoxadiazoles with the tethered imine moiety leading to 1ꢀ
unsubstituted aminoimidazoles.15 Recently, several research groups reported the synthesis of 4ꢀ
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sulfonamidoimidazoles by intermolecular transannulation reactions of 1,2,4ꢀoxadiazole derivatives
with Nꢀalkynyl sulfonamides.16 In particular, 4ꢀsulfonamidoimidazoles were prepared from 1,2,4ꢀ
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 αꢀcarbon atom of the alkyne to form exclusively 4ꢀaminoimidazole derivatives and neither
of them is applicable to the synthesis of regioisomeric 5ꢀaminoimidazoles. In a search of suitable
reaction partners for the 1,2,4ꢀoxadiazoles, which would provide the reverse regioselectivity of the
transannulation, we considered 1ꢀsulfonylꢀ1,2,3ꢀtriazoles 3.17 These compounds have recently been
used as the precursors of αꢀimino Rh(II) carbenoids in the synthesis of aminofurans and aminoꢀ
pyrroles.18
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Scheme 2. Synthesis of 4ꢀ and 5ꢀAminoimidazoles from 1,2,4ꢀOxadiazole Derivatives
Until the current year,19 reactions of both 1,2,4ꢀoxadiazoles 1 and 1,2,4ꢀoxadiazolꢀ5ꢀones 2 with
carbenoids were unknown, and the question as to whether carbenoids can transform these N,N,Oꢀ
heterocycles remained open.
In this work, we report a method for the synthesis of 5ꢀaminoimidazoles 4 and 5 by the intermoꢀ
lecular transannulation reaction of readily available 1,2,4ꢀoxadiazole derivatives with 1ꢀsulfonylꢀ
1,2,3ꢀtriazoles under rhodium(II) catalysis (Scheme 2, reaction B).
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Results and Discussion
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We began our study by exploring the reaction of 5ꢀmethoxyꢀ1,2,4ꢀoxadiazole 1a and 1ꢀsulfonylꢀ
1,2,3ꢀtriazole 3a in the presence of rhodium(II) carboxylates (Scheme 3). In the molecule of oxadiaꢀ
zole 1a there are two nucleophilic nitrogen atoms that can be attacked by αꢀimino 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 5ꢀ
sulfonamidoimidazole 4a. An alternative pathway b would lead to the 4ꢀaminoꢀsubstituted isomer
4a'.
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Scheme 3. Possible Pathways for the Rh(II)ꢀcatalyzed Reaction of Oxadiazole 1a with Triazole
3a
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 1,2ꢀdichloroethane (DCE) at 100 °C (3
equiv. of the triazole in one portion) gave the desired 5ꢀaminoimidazole 4a in 50% yield. Although
the triazole completely decomposed in the reaction, ca. 45% of 1a left unreacted (entry 2). This reꢀ
sult 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
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(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 soluꢀ
tion in DCE at 84 °C with 5 mol % of Rh2(Piv)4 as a catalyst (entry 6).
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Table 1. Optimization of Conditions for 4a Synthesis a
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entry catalystb
Т (°C)
Rh2(OAc)4 120
Rh2(Piv)4 100
yield of 4a, %c
1d
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Rh2(Piv)4 100
Rh2(esp)2 100
Rh2(Oct)4 100
Rh2(Piv)4 84
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93 (91)e
aReaction conditions: addition of 3a (0.3 mmol) to a solution of 1a (0.1 mmol) in portions of 0.05
mmol. Piv = pivalate, esp = α,α,α′,α′ꢀtetramethylꢀ1,3ꢀbenzenedipropanoate, Oct = octanoate. c1H
b
NMR yields using CH2Br2 as an internal standard. Addition of 3 equiv. of 3a in one portion. e Isoꢀ
d
lated yield.
With the optimized conditions, we then explored the scope of the reaction using a series of
1,2,4ꢀoxadiazoles 1 and 1ꢀsulfonylꢀ1,2,3ꢀtriazoles 3 (Scheme 4). It was found that the reaction tolerꢀ
ates both electronꢀdonating and electronꢀwithdrawing aryl substituents as well as naphthyl and benꢀ
zyl groups at the C3 of 1,2,4ꢀoxadiazole (imidazoles 4a–p).
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Scheme 4. Scope of Imidazoleꢀ1ꢀcarboxylatesa
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a Reaction conditions: 1 (0.2 mmol), 3 (0.6 mmol), Rh2(Piv)4 (5 mol %), DCE (0.5 mL), 84 °C, 30
min; b 3 (0.5 mmol); c 3 (0.4 mmol); d 3 (0.8 mmol).
In contrast to the benzyl ester (imidazole 4q), which was synthesized in excellent yield, tertꢀ
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 4ꢀarylꢀ1ꢀsulfonylꢀ1,2,3ꢀtriazoles were also suitable for the reaction and gave 5ꢀ
aminoimidazoles 4t–z,za in good yields. 1ꢀMesylꢀ1,2,3ꢀtriazole 3g afforded the corresponding imidꢀ
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azole 4y in slightly lower yield and 4 equiv. of the triazole were required for full conversion of the
oxadiazole.
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Next we studied the reactivity of 4ꢀalkylꢀ1,2,4ꢀoxadiazolꢀ5ꢀones 2 towards 1ꢀsulfonylꢀ1,2,3ꢀ
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 condiꢀ
tions (DCE, 84 °C).
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Scheme 5. Scope of 1ꢀAlkylimidazolesa
aReaction conditions: 2 (0.2 mmol), 3 (0.24 mmol), Rh2(Piv)4 (5 mol %), DCE (0.5 mL), 84 °C,
5 min.
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When Rh2(OAc)4 was replaced by Rh2(Piv)4 (5 mol %), however, the reaction was completed in
several minutes, giving Nꢀmethylated 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 1ꢀmethylimidazoles 5a–k were synthesized in excellent yields from various 3ꢀarylꢀ and
3ꢀalkylꢀsubstituted 1,2,4ꢀoxadiazolꢀ5ꢀones 2.
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1ꢀBenzylimidazole 5l was also obtained in 94% yield. The high yields of imidazoles 5m−s deꢀ
rived from different 4ꢀarylꢀ1ꢀsulfonylꢀ1,2,3ꢀtriazoles 3 pointed to a rather low sensitivity of the reacꢀ
tion towards 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
1
chromatography. The structures of all synthesized compounds were verified by H and 13C NMR
spectroscopy and HRMS. The structures of imidazoleꢀ1ꢀcarboxylate 4e and 1ꢀmethylimidazole 5a
were confirmed by Xꢀray diffraction analysis (Scheme 4, 5).20
To test whether the reaction could be scaledꢀup, a gramꢀscale synthesis of 1ꢀmethylimidazole 5e
was carried out with a reduced loading of Rh2(Piv)4 (1 mol %). As the result, imidazole 5e was isoꢀ
lated 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 1,2,4ꢀoxadiazoles 1/1,2,4ꢀ
oxadiazolꢀ5ꢀones 2 and 1ꢀsulfonylꢀ1,2,3ꢀtriazoles 3 are depicted in Scheme 6. αꢀImino rhodium carꢀ
benoid 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 1,3,6ꢀtriazatriene 8a (R = CO2Me) likely occurs
in a oneꢀstep via simultaneous cleavage of the C−Rh and N−O bonds.
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Scheme 6. Proposed Mechanisms for the Formation of Imidazoles 4, 5
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The reaction of carbenoid 7 with 1,2,4ꢀoxadiazolꢀ5ꢀone 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 1,3,6ꢀtriazahexaꢀ1,3,5ꢀtriene intermediate 8b (R = Me). The subseꢀ
quent 5ꢀexoꢀtrigꢀcyclization of intermediates 8 and prototropic shift leads to imidazoles 4a and 5a. It
is worthy of note that in contrast to 3ꢀazaꢀ,21 1,4ꢀdiazaꢀ18a−d,22 and 1,5ꢀdiazahexaꢀ1,3,5ꢀtrienes,23 the
generation of 1,3,6ꢀtriazahexaꢀ1,3,5ꢀtriene species has never been reported earlier. Triazahexatrienes
8 can, in principle, undergo two competing 1,5ꢀcyclizations leading either to 4Hꢀimidazolium betaꢀ
ines 11 (the N1−C5 bond formation) or their 2Hꢀregioisomers (not shown) (the C2−N6 bond forꢀ
mation). The obtained results showed that triazahexatrienes 8 cyclize into 4Hꢀimidazolium betaines
exclusively, but not their 2H regioisomers, even in the case of triazatriene 8a with the electronꢀ
withdrawing N1ꢀsubstituent (R = CO2Me).
It is known that some 5ꢀaminoimidazoleꢀ1ꢀcarboxylates at elevated temperatures can undergo
isomerization via ester group transfer from the endocyclic to the exocyclic nitrogen atom.24 Unexꢀ
pectedly, it was found that at 190−200 °C 1ꢀmethoxycarbonylꢀsubstituted imidazoles 4 undergo deꢀ
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carboxylation with simultaneous transfer of a methyl group to sulfonamide nitrogen. Thus, imidazꢀ
ole 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.
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Scheme 7. Formation of NHꢀimidazole 12
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Ph
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190 C
neat
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Ts
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R
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N
N
H
N
- CO2
Me
O
OMe
O
OMe
12, 67%
4g
R = 4-ClC6H4
Conclusion
In conclusion, we have developed a convenient synthesis of fully substituted 5ꢀ
sulfonamidoimidazoles by Rh2(Piv)4ꢀcatalyzed transannulation of 1,2,4ꢀoxadiazole derivatives with
Nꢀsulfonylꢀ1,2,3ꢀtriazoles. The flexibility of the method, which efficiently works with both 1,2,4ꢀ
oxadiazoles and 1,2,4ꢀoxadiazolꢀ5ꢀones, allows the introduction of various substituents in all posiꢀ
tions 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 chromatographyꢀfree
manner. The smooth formation of 5ꢀsulfonamidoimidazoles in both reactions is ensured by the reꢀ
gioselectivity of the two key stages of the domino sequences, namely carbenoidꢀmediated oxadiaꢀ
zole ring opening and 5ꢀexoꢀtrigꢀcyclization of 1,3,6ꢀtriazahexatriene intermediate.
Experimental Section
General Methods. Melting points were determined on a melting point apparatus and are unꢀ
1
13
corrected. H (400 MHz) and C (100 MHz) NMR spectra were recorded in solvents indicated beꢀ
low. Chemical shifts (δ) are reported in parts per million downfield from tetramethylsilane. Highꢀ
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resolution mass spectra were recorded on an HRMSꢀESIꢀQTOF instrument, electrospray ionization,
positive mode. Thinꢀlayer 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). 1,2ꢀDichloroethane was washed with concentrated H2SO4 and water, distilled
from P2O5, and stored over anhydrous K2CO3. Tetrahydrofuran was distilled and stored over sodium
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metal. DMSO was purchased and used without further purification. The catalysts Rh2(Oct)4 ,
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Rh2(Piv)4 , and Rh2(esp)2 were prepared by the reported procedures and gave satisfactory eleꢀ
mental analyses. 3ꢀ(4ꢀBromophenyl)ꢀN,Nꢀdimethylꢀ1,2,4ꢀoxadiazolꢀ5ꢀamine (1s),28 4ꢀbenzylꢀ3ꢀ
phenylꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (2q),16b and triazoles 3a−e,g−i29 were synthesized according to
the published procedures and they have full characterization data. 5ꢀMethoxyꢀ1,2,4ꢀoxadiazoles 130
and 4ꢀmethylꢀ1,2,4ꢀoxadiazolꢀ5(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, 1,2,4ꢀoxadiazolꢀ5(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 1,2,4ꢀoxadiazolꢀ5(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 temꢀ
perature 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 waꢀ
ter (10 mL) and dried in air at 50 °C.
3ꢀPhenylꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (A).13 White solid (1.17 g, yield 72%). Mp 195−196 °C.
1H NMR (DMSOꢀd6): δ 13.19 (br. s, 1H), 7.90−7.83 (m, 2H), 7.65−7.54 (m, 3H). 13C NMR
(DMSOꢀd6): 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.
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3ꢀ(4ꢀMethylphenyl)ꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (B).13 White solid (1.23 g, yield 70%). Mp
221−223 °C. 1H NMR (DMSOꢀd6): 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 (DMSOꢀd6): δ 160.5, 157.9, 142.8, 130.3, 126.5, 121.0, 21.6.
8
9
+
HRMS−ESI: [M + Na]+ calcd for C9H8N2NaO2 , 199.0478; found, 199.0484.
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3ꢀ(2ꢀMethylphenyl)ꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (C).33 White solid (1.09 g, yield 62%). Mp
156−157 °C. 1H NMR (DMSOꢀd6): δ 12.66 (br. s, 1H), 7.57 (dd, J = 7.7, 1.3 Hz, 1H), 7.51 (td, J =
13
7.6 Hz, 1H), 7.44−7.35 (m, 2H), 2.46 (s, 3H). C NMR (DMSOꢀd6): 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.
3ꢀ(4ꢀMethoxyphenyl)ꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (D).13 White solid (1.31 g, yield 68%). Mp
209−211 °C. 1H NMR (DMSOꢀd6): 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 (DMSOꢀd6): 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.
3ꢀ(4ꢀFluorophenyl)ꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (E).13 White solid (1.03 g, yield 57%). Mp
1
13
228−229 °C. H NMR (DMSOꢀd6): δ 13.14 (br. s, 1H), 7.94−7.88 (m, 2H), 7.46−7.39 (m, 2H). C
NMR (DMSOꢀd6): 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.
3ꢀ(3ꢀFluorophenyl)ꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (F). White solid (1.01 g, yield 56%). Mp
1
188−189 °C. H NMR (DMSOꢀd6): δ 13.39 (br. s, 1H), 7.76−7.70 (m, 2H), 7.66−7.59 (m, 1H),
13
7.51−7.44 (m, 1H). C NMR (DMSOꢀd6): 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.
+
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3ꢀ(4ꢀChlorophenyl)ꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (G).13 White solid (1.24 g, yield 63%). Mp
1
13
280−282 °C. H NMR (DMSOꢀd6): δ 13.04 (br. s, 1H), 7.86−7.80 (m, 2H), 7.70−7.64 (m, 2H). C
5
6
7
NMR (DMSOꢀd6): δ 160.3, 157.1, 137.4, 130.0, 128.3, 122.7. HRMS−ESI: [M + Na]+ calcd for
8
9
35
+
C8H5 ClN2NaO2 , 218.9932; found, 218.9940.
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3ꢀ(3ꢀChlorophenyl)ꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (H). White solid (1.06 g, yield 54%). Mp
185−186 °C. 1H NMR (DMSOꢀd6): δ 13.02 (br. s, 1H), 7.87−7.56 (m, 4H). 13C NMR (DMSOꢀd6): δ
160.2, 156.8, 134.4, 132.5, 131.7, 126.3, 125.8, 125.2. HRMS−ESI: [M + H]+ calcd for
35
+
C8H6 ClN2O2 , 197.0112; found, 197.0118.
3ꢀ(4ꢀBromophenyl)ꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (I).33 White solid (1.44 g, yield 60%). Mp
291−293 °C. 1H NMR (DMSOꢀd6): δ 13.03 (br. s, 1H), 7.84−7.71 (m, 4H). 13C NMR (DMSOꢀd6): δ
79
+
160.3, 157.2, 132.9, 128.4, 126.3, 123.0. HRMS−ESI: [M + Na]+ calcd for C8H5 BrN2NaO2 ,
262.9427; found, 262.9438.
3ꢀ[4ꢀ(Trifluoromethyl)phenyl]ꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (J).13 White solid (1.27 g, yield
55%). Mp 267−269 °C. 1H NMR (DMSOꢀd6): δ 13.23 (br. s, 1H), 8.03 (d, J = 8.3 Hz, 2H), 7.97 (d,
J = 8.3 Hz, 2H). 13C NMR (DMSOꢀd6): 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.
3ꢀ[3ꢀ(Trifluoromethyl)phenyl]ꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (K).13 White solid (1.43 g, yield
62%). Mp 171−173 °C. 1H NMR (DMSOꢀd6) 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 (DMSOꢀd6): 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.
3ꢀ(4ꢀNitrophenyl)ꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (L).13 Yellow solid (1.20 g, yield 58%). Mp
304−306 °C (dec.). 1H NMR (DMSOꢀd6): δ 13.37 (br. s, 1H), 8.41 (d, J = 8.9 Hz, 2H), 8.09 (d, J =
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8.9 Hz, 2H). C NMR (DMSOꢀd6): δ 160.2, 156.7, 149.9, 129.6, 128.1, 124.9. HRMS−ESI [M −
−
H]− calcd for C8H4N3O4 , 206.0207; found, 206.0197.
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3ꢀ(Naphthalenꢀ1ꢀyl)ꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (M). White solid (1.80 g, yield 85%). Mp
184−186 °C. 1H NMR (DMSOꢀd6): 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 (DMSOꢀd6): 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
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+
+ Na]+ calcd for C12H8N2NaO2 , 235.0478; found, 235.0489.
3ꢀ(Naphthalenꢀ2ꢀyl)ꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (N).13 White solid (1.38 g, yield 65%). Mp
212−214 °C. 1H NMR (DMSOꢀd6): 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 (DMSOꢀd6): 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.
+
3ꢀBenzylꢀ1,2,4ꢀoxadiazolꢀ5(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,
1
washed with Et2O and dried in air. White solid (581 mg, yield 33%). Mp 104−106 °C. H 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.
3ꢀ(3ꢀMethoxybenzyl)ꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (P). Obtained according to the general proceꢀ
dure. 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
1
filtered off, washed with Et2O and dried in air. White solid (1.34 g, yield 65%). Mp 89−91 °C. H
NMR (DMSOꢀd6): δ 12.28 (br. s, 1H), 7.27 (t, J = 7.8 Hz, 1H), 6.90−6.84 (m, 3H), 3.84 (s, 2H),
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3.75 (s, 3H). C NMR (DMSOꢀd6): 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.
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General Procedure for the Preparation of 5ꢀmethoxyꢀ1,2,4ꢀoxadiazoles 1 and
4ꢀmethylꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀones 2.35 To a stirred solution of diazomethane in Et2O (10
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mL), prepared from NꢀmethylꢀNꢀnitrosourea (10 mmol) and KOH (46 mmol), 1,2,4ꢀoxadiazolꢀ
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 puriꢀ
fied by column chromatography on silica gel (eluent petroleum ether−Et2O 3:1) to give 5ꢀmethoxyꢀ
1,2,4ꢀoxadiazole 1 and 4ꢀmethylꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone 2.
5ꢀMethoxyꢀ3ꢀphenylꢀ1,2,4ꢀoxadiazole (1a)30 and 4ꢀmethylꢀ3ꢀphenylꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone
(2a)16b were obtained according to the general procedure from oxadiazolone A. Compound 1a: white
1
solid (326 mg, yield 37%). Mp 35−37 °C. Rf = 0.55 (hexane−Et2O, 2:1). H 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
13
NMR (CDCl3): δ 7.68−7.54 (m, 5H), 3.34 (s, 3H). C 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.
5ꢀMethoxyꢀ3ꢀ(4ꢀmethylphenyl)ꢀ1,2,4ꢀoxadiazole (1b)30 and 4ꢀmethylꢀ3ꢀ(4ꢀmethylphenyl)ꢀ1,2,4ꢀ
oxadiazolꢀ5(4H)ꢀone (2b)31 were obtained according to the general procedure from oxadiazolone B.
1
Compound 1b: white solid (409 mg, yield 43%). Mp 35−37 °C. Rf = 0.55 (hexane−Et2O, 2:1). H
13
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). C 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.
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Compound 2b: white solid (485 mg, yield 51%). Mp 98−99 °C. Rf = 0.12 (hexane−Et2O, 2:1). H
13
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). C
5
6
7
NMR (CDCl3): δ 159.8, 158.8, 142.8, 130.0, 128.0, 120.3, 29.7, 21.5. HRMS−ESI: [M + Na]+ calcd
8
9
+
for C10H10N2NaO2 , 213.0634; found, 213.0642.
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5ꢀMethoxyꢀ3ꢀ(2ꢀmethylphenyl)ꢀ1,2,4ꢀoxadiazole (1c) and 4ꢀmethylꢀ3ꢀ(2ꢀmethylphenyl)ꢀ1,2,4ꢀ
oxadiazolꢀ5(4H)ꢀone (2c) were obtained according to the general procedure from oxadiazolone C.
1
Compound 1c: white solid (371 mg, yield 39%). Mp 53−55 °C. Rf = 0.63 (hexane−Et2O, 2:1). H
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). 13C 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: colorꢀ
+
less 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.
5ꢀMethoxyꢀ3ꢀ(4ꢀmethoxyphenyl)ꢀ1,2,4ꢀoxadiazole (1d) and 3ꢀ(4ꢀmethoxyphenyl)ꢀ4ꢀmethylꢀ
1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (2d)16b were obtained according to the general procedure from oxadiaꢀ
zolone D. Compound 1d: white solid (402 mg, yield 39%). Mp 72−73 °C. Rf = 0.49 (hexane−Et2O,
1
1:1). H 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
1
94−95 °C. Rf = 0.11 (hexane−Et2O, 1:1). H 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.
+
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3ꢀ(4ꢀFluorophenyl)ꢀ5ꢀmethoxyꢀ1,2,4ꢀoxadiazole (1e). This compound was obtained according
to the general procedure from oxadiazolone E. White solid (330 mg, yield 34%). Mp 41−42 °C. Rf =
6
7
1
0.53 (hexane−Et2O, 2:1). H NMR (CDCl3) δ 8.06−8.01 (m, 2H), 7.21−7.13 (m, 2H), 4.29 (s, 3H).
8
9
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
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+
Hz), 115.9 (d, J = 22.0 Hz), 60.3. HRMS−ESI: [M + H]+ calcd for C9H8FN2O2 , 195.0564; found,
195.0571. The corresponding 4ꢀmethylꢀ1,2,4ꢀoxadiazolone was not isolated.
3ꢀ(3ꢀFluorophenyl)ꢀ5ꢀmethoxyꢀ1,2,4ꢀoxadiazole (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 4ꢀ
+
methylꢀ1,2,4ꢀoxadiazolone was not isolated.
3ꢀ(4ꢀChlorophenyl)ꢀ5ꢀmethoxyꢀ1,2,4ꢀoxadiazole (1g) and 3ꢀ(4ꢀchlorophenyl)ꢀ4ꢀmethylꢀ1,2,4ꢀ
oxadiazolꢀ5(4H)ꢀone (2g)16b 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
35
+
for C9H7 ClN2NaO2 , 233.0088; found, 233.0080.
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3ꢀ(3ꢀChlorophenyl)ꢀ5ꢀmethoxyꢀ1,2,4ꢀoxadiazole (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,
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9
13
1H), 7.42 (t, J = 7.8 Hz, 1H), 4.29 (s, 3H). C NMR (CDCl3): δ 174.1, 167.9, 134.8, 131.2, 130.0,
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+
128.8, 127.2, 125.0, 60.4. HRMS−ESI: [M + H]+ calcd for C9H8 ClN2O2 , 211.0269; found,
211.0272. The corresponding 4ꢀmethylꢀ1,2,4ꢀoxadiazolone was not isolated.
3ꢀ(4ꢀBromophenyl)ꢀ5ꢀmethoxyꢀ1,2,4ꢀoxadiazole (1i). This compound was obtained according to
the general procedure from oxadiazolone I. White solid (610 mg, yield 48%). Mp 76−77 °C. Rf =
1
0.59 (hexane−Et2O, 2:1). H 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
79
+
for C9H7 BrN2NaO2 , 276.9583; found, 276.9571. The corresponding 4ꢀmethylꢀ1,2,4ꢀoxadiazolone
was not isolated.
5ꢀMethoxyꢀ3ꢀ[4ꢀ(trifluoromethyl)phenyl]ꢀ1,2,4ꢀoxadiazole
(1j)
and
4ꢀmethylꢀ3ꢀ[4ꢀ
(trifluoromethyl)phenyl]ꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone (2j) were obtained according to the general proꢀ
cedure from oxadiazolone J. Compound 1j: white solid (634 mg, yield 52%). Mp 38−40 °C. Rf =
1
0.62 (hexane−Et2O, 2:1). H NMR (CDCl3): δ 8.16 (d, J = 8.2 Hz, 2H), 7.75 (d, J = 8.2 Hz, 2H),
13
4.31 (s, 3H). C 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 (hexꢀ
ane−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.
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5ꢀMethoxyꢀ3ꢀ[3ꢀ(trifluoromethyl)phenyl]ꢀ1,2,4ꢀoxadiazole (1k). This compound was obtained
according to the general procedure from oxadiazolone K. White solid (622 mg, yield 51%). Mp
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30−31 °C. Rf = 0.50 (hexane−Et2O, 2:1). H NMR (CDCl3): δ 8.31 (br. s, 1H), 8.23 (d, J = 7.8 Hz,
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9
13
1H), 7.78 (d, J = 7.8 Hz, 1H), 7.63 (t, J = 7.8 Hz, 1H), 4.32 (s, 3H). C NMR (CDCl3): δ 174.3,
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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 4ꢀmethylꢀ1,2,4ꢀoxadiazolone was not isolated.
5ꢀMethoxyꢀ3ꢀ(4ꢀnitrophenyl)ꢀ1,2,4ꢀoxadiazole (1l) and 4ꢀmethylꢀ3ꢀ(4ꢀnitrophenyl)ꢀ1,2,4ꢀ
oxadiazolꢀ5(4H)ꢀone (2l) 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 =
1
0.07 (hexane−Et2O, 1:1). H 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.
+
5ꢀMethoxyꢀ3ꢀ(naphthalenꢀ1ꢀyl)ꢀ1,2,4ꢀoxadiazole (1m) and 4ꢀmethylꢀ3ꢀ(naphthalenꢀ1ꢀyl)ꢀ1,2,4ꢀ
oxadiazolꢀ5(4H)ꢀone (2m)16b 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). 13C 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
+
1
solid (633 mg, yield 56%). Mp 58−60 °C. Rf = 0.09 (hexane−Et2O, 2:1). H NMR (CDCl3): δ
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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
4
5
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,
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7
+
120.3, 29.2. HRMS−ESI: [M + Na]+ calcd for C13H10N2NaO2 , 249.0634; found, 249.0625.
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5ꢀMethoxyꢀ3ꢀ(naphthalenꢀ2ꢀyl)ꢀ1,2,4ꢀoxadiazole (1n) and 4ꢀmethylꢀ3ꢀ(naphthalenꢀ2ꢀyl)ꢀ1,2,4ꢀ
oxadiazolꢀ5(4H)ꢀone (2n) were obtained according to the general procedure from oxadiazolone N.
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Compound 1n: white solid (520 mg, yield 46%). Mp 88−89 °C. Rf = 0.45 (hexane−Et2O, 2:1). H
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 (hexꢀ
ane−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.
3ꢀBenzylꢀ5ꢀmethoxyꢀ1,2,4ꢀoxadiazole (1o) and 3ꢀbenzylꢀ4ꢀmethylꢀ1,2,4ꢀoxadiazolꢀ5(4H)ꢀone
(2o)16b were obtained according to the general procedure from oxadiazolone O. Compound 1o: colꢀ
1
orless oil (371 mg, yield 39%). H 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
1
53%). Mp 106−108 °C. Rf = 0.07 (hexane−Et2O, 2:1). H 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.
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5ꢀMethoxyꢀ3ꢀ(3ꢀmethoxybenzyl)ꢀ1,2,4ꢀoxadiazole (1p) and 3ꢀ(3ꢀmethoxybenzyl)ꢀ4ꢀmethylꢀ1,2,4ꢀ
oxadiazolꢀ5(4H)ꢀone (2p) were obtained according to the general procedure from oxadiazolone P.
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Compound 1p: yellow oil (231 mg, yield 21%). Rf = 0.39 (hexane−Et2O, 1:1). H NMR (CDCl3): δ
8
9
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
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13
(s, 3H), 3.92 (s, 2H), 3.82 (s, 3H). C 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
1:1). H 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 5ꢀBenzyloxyꢀ3ꢀphenylꢀ1,2,4ꢀoxadiazole (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 5ꢀchloroꢀ3ꢀphenylꢀ1,2,4ꢀoxadiazole37 (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 comꢀ
bined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. Puꢀ
rification by column chromatography on silica gel (eluent hexane−EtOAc, 5:1) afforded crude prodꢀ
1
uct (≈90% purity) which was used in further experiments. Colorless oil (83 mg, yield 40%). H
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 5ꢀ(tertꢀButoxy)ꢀ3ꢀphenylꢀ1,2,4ꢀoxadiazole (1r). A solution of 5ꢀ
chloroꢀ3ꢀphenylꢀ1,2,4ꢀoxadiazole37 (2 mmol) and tꢀBuOK (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
1
the oxadiazole 1r as a white solid (332 mg, yield 76%). Mp 29−30 °C. H NMR (CDCl3): δ
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8.07−8.02 (m, 2H), 7.53−7.45 (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,
5
6
7
241.0950.
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Synthesis of 1ꢀ(4ꢀMethylphenylsulfonyl)ꢀ4ꢀ(4ꢀnitrophenyl)ꢀ1Hꢀ1,2,3ꢀtriazole
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(3f). Triazole 3f was prepared by reported procedure29 as a white solid (yield 52%). Mp 191−193
°C (dec.). 1H 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 (DMSOꢀd6): 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 imidazoleꢀ1ꢀcarboxylates 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, nameꢀ
ly, by filtration of the reaction mixture, washing of the product with Et2O−hexane mixture and dryꢀ
ing under reduced pressure.
Methyl 5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ2,4ꢀdiphenylꢀ1Hꢀimidazoleꢀ1ꢀcarboxylate (4a). This
compound was obtained according to the general procedure from oxadiazole 1a and triazole 3a (0.6
1
mmol) as a white solid (81 mg, yield 91%). Mp 196−197 °C (dec.). H NMR (DMSOꢀd6): 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,
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J = 8.2 Hz, 2H), 3.76 (s, 3H), 2.24 (s, 3H). 13C NMR (DMSOꢀd6): 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.
8
9
Methyl
2ꢀ(4ꢀmethylphenyl)ꢀ5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ4ꢀphenylꢀ1Hꢀimidazoleꢀ1ꢀ
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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
2ꢀ(2ꢀmethylphenyl)ꢀ5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ4ꢀphenylꢀ1Hꢀimidazoleꢀ1ꢀ
carboxylate (4c). This compound was obtained according to the general procedure from oxadiazole
1
1c and triazole 3a (0.6 mmol) as a white solid (89 mg, yield 96%). Mp 87−89 °C (dec.). H 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
2ꢀ(4ꢀmethoxyphenyl)ꢀ5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ4ꢀphenylꢀ1Hꢀimidazoleꢀ1ꢀ
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
(DMSOꢀd6): 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
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(DMSOꢀd6): 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.
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carboxylate (4e). This compound was obtained according to the general procedure from oxadiazole
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1e and triazole 3a (0.5 mmol) as a white solid (79 mg, yield 85%). Mp 186−187 °C (dec.). H 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
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= 8.1 Hz, 2H), 6.80 (br. s, 1H), 3.83 (s, 3H), 2.31 (s, 3H). C 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
2ꢀ(3ꢀfluorophenyl)ꢀ5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ4ꢀphenylꢀ1Hꢀimidazoleꢀ1ꢀ
carboxylate (4f). This compound was obtained according to the general procedure from oxadiazole
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1f and triazole 3a (0.6 mmol) as a white solid (91 mg, yield 98%). Mp 161−162 °C (dec.). H 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
2ꢀ(4ꢀchlorophenyl)ꢀ5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ4ꢀphenylꢀ1Hꢀimidazoleꢀ1ꢀ
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
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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.
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Methyl
2ꢀ(3ꢀchlorophenyl)ꢀ5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ4ꢀphenylꢀ1Hꢀimidazoleꢀ1ꢀ
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
2ꢀ(4ꢀbromophenyl)ꢀ5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ4ꢀphenylꢀ1Hꢀimidazoleꢀ1ꢀ
carboxylate (4i). This compound was obtained according to the general procedure from oxadiazole
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1i and triazole 3a (0.6 mmol) as a white solid (94 mg, yield 89%). Mp 187−188 °C (dec.). H 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 5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ4ꢀphenylꢀ2ꢀ[4ꢀ(trifluoromethyl)phenyl]ꢀ1Hꢀimidazoleꢀ1ꢀ
carboxylate (4j). This compound was obtained according to the general procedure from oxadiazole
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1j and triazole 3a (0.6 mmol) as a white solid (89 mg, yield 86%). Mp 148−149 °C (dec.). H 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,
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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.
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carboxylate (4k). This compound was obtained according to the general procedure from oxadiazole
1k and triazole 3a (0.6 mmol) as a white solid (93 mg, yield 90%). Mp 177−178 °C (dec.). 1H NMR
(DMSOꢀd6): 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 (DMSOꢀd6): 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.
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Methyl 5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ2ꢀ(4ꢀnitrophenyl)ꢀ4ꢀphenylꢀ1Hꢀimidazoleꢀ1ꢀcarboxylate
(4l). This compound was obtained according to the general procedure from oxadiazole 1l and triaꢀ
zole 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
5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ2ꢀ(naphthalenꢀ1ꢀyl)ꢀ4ꢀphenylꢀ1Hꢀimidazoleꢀ1ꢀ
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
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(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.
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Methyl
5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ2ꢀ(naphthalenꢀ2ꢀyl)ꢀ4ꢀphenylꢀ1Hꢀimidazoleꢀ1ꢀ
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
(DMSOꢀd6): 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,
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2H), 3.78 (s, 3H), 2.25 (s, 3H). C NMR (DMSOꢀd6): 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 2ꢀbenzylꢀ5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ4ꢀphenylꢀ1Hꢀimidazoleꢀ1ꢀcarboxylate (4o).
This compound was obtained according to the general procedure from oxadiazole 1o and triazole 3a
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(0.4 mmol) as a white solid (90 mg, yield 98%). Mp 162−164 °C (dec.). H 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
2ꢀ(3ꢀmethoxybenzyl)ꢀ5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ4ꢀphenylꢀ1Hꢀimidazoleꢀ1ꢀ
carboxylate (4p). This compound was obtained according to the general procedure from oxadiazole
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1p and triazole 3a (0.4 mmol) as a white solid (78 mg, yield 79%). Mp 132−133 °C. H NMR
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(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,
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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). C NMR
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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.
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Benzyl 5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ2,4ꢀdiphenylꢀ1Hꢀimidazoleꢀ1ꢀcarboxylate (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 (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
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= 8.1 Hz, 2H), 5.14 (s, 2H), 2.23 (s, 3H) (NH signal is not observed). C 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.
2ꢀ(4ꢀBromophenyl)ꢀN,Nꢀdimethylꢀ5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ4ꢀphenylꢀ1Hꢀimidazoleꢀ1ꢀ
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
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mmol) as a white solid (70 mg, yield 65%). Mp 137−139 °C (dec.). H 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
4ꢀ(4ꢀmethoxyphenyl)ꢀ5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ2ꢀphenylꢀ1Hꢀimidazoleꢀ1ꢀ
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
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(DMSOꢀd6): 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
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(d, J = 8.0 Hz, 2H), 6.74−6.69 (m, 2H), 3.75 (s, 6H), 2.25 (s, 3H). C NMR (DMSOꢀd6): δ 159.1,
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113.7, 55.5, 55.4, 21.3. HRMS−ESI: [M + H]+ calcd for C25H24N3O5S+, 478.1431; found, 478.1445.
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Methyl
4ꢀ(2ꢀfluorophenyl)ꢀ5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ2ꢀphenylꢀ1Hꢀimidazoleꢀ1ꢀ
carboxylate (4u). This compound was obtained according to the general procedure from oxadiazole
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1a and triazole 3c (0.6 mmol) as a white solid (83 mg, yield 89%). Mp 187−188 °C (dec.). H NMR
(DMSOꢀd6): 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
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(m, 4H), 3.81 (s, 3H), 2.25 (s, 3H). C NMR (DMSOꢀd6): 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
4ꢀ(4ꢀchlorophenyl)ꢀ5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ2ꢀphenylꢀ1Hꢀimidazoleꢀ1ꢀ
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
(DMSOꢀd6): 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 (DMSOꢀd6): 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 5ꢀ(4ꢀmethylphenylsulfonamido)ꢀ2ꢀphenylꢀ4ꢀ[4ꢀ(trifluoromethyl)phenyl]ꢀ1Hꢀimidazoleꢀ1ꢀ
carboxylate (4w). This compound was obtained according to the general procedure from oxadiazole
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1a and triazole 3e (0.6 mmol) as a white solid (82 mg, yield 80%). Mp 198−199 °C (dec.). H NMR
(DMSOꢀd6): 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
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