Oxone^®-Promoted One-Pot Synthesis of 1-Aryl-4-(organylselanyl)-1H-pyrazoles

Abstract

We describe herein an efficient protocol for the one-pot synthesis of 4-organylselanylpyrazoles by direct cyclocondensation and C-H bond selenylation reactions starting from hydrazines, 1,3-diketones and diorganyl diselenides promoted by Oxone^®. The products were obtained through a metal catalyst free methodology, under mild conditions, in short reaction times and moderate to excellent yields.

Keywords:
Oxone^®; organoselenium compounds; pyrazoles

Introduction

Pyrazoles have synthetic interest due to its numerous biological activities^1-5 such as, anti-inflammatory properties (celecoxib),^6,7 insecticidal effects (fipronil),⁸ analgesic effects (metamizole),⁹ treatment of erectile dysfunction (sildenafil)¹⁰ and sedative-hypnotic agents (zaleplon).¹¹ Regarding the available methods for the synthesis of pyrazoles, these structures are usually synthesized by the 1,3-dipolar cycloaddition reaction using alkenes or alkynes,^12,13 reacting unsaturated ketones or aldehydes with hydrazines^14-16 and the condensation reaction of 1,3-dicarbonyl compounds with hydrazines.^17-19

In addition, organoselenium compounds are attractive synthetic targets due to their applicability in organic synthesis in selective reactions,^20-23 chiral catalysts,^24,25 photophysical properties^26-28 and pharmacological activities.^29-37 Thus, the presence of selenium in the pyrazole ring could result in compounds with new pharmacological and medicinal activities.

In recent years, several methods to synthesize 4-(arylselanyl)pyrazoles were reported.^38-42 However, these protocols usually require pre-functionalization of substrates,^38-40 use of transition metals as catalysts,⁴¹ multi-step synthesis and long reaction times. In 2015, our research group⁴¹ reported the direct synthesis of 4-(organylselanyl)pyrazoles by copper-catalyzed one-pot cyclocondensation and C-H bond selenylation reactions starting from hydrazines, 1,3-diketones and diorganoyl diselenides (Scheme 1).

Recently, Zora et al.⁴² reported the one-pot preparation of 4-phenylselanyl-1H-pyrazoles through electrophilic cyclization of α,β-alkynil hydrazones with phenylselanyl chloride (Scheme 2).

Scheme 1
Synthesis of 4-arylselanylpyrazoles by copper-catalyzed one-pot cyclization.⁴¹

Scheme 2
Synthesis of 4-(phenylselanyl)pyrazole via electrophilic cyclization.⁴²

The potassium peroxymonosulfate exists as a stable triple salt (2KHSO₅^.KHSO₄^.K₂SO₄), it is a white crystallin solid known as trademark Oxone^®. In recently years, the use of Oxone^® has shown an efficient alternative to traditional oxidants in organic synthesis. As oxidizing agent it has many advantages, such as water solubility, stability under several conditions, simplicity in handling, cheap, not toxic acid, easy-to-handle and environmentally safe (generates nonpolluting by-products).⁴³ Recently, the Oxone^® has been used in the preparation of important heterocycles, for example in the synthesis of pyrazoles,⁴⁴ benzoxazoles and benzimidazoles.^45,46 Other examples are included, such as synthesis of isoxazolines and isoxazoles,⁴⁷ chromene and carbazole,⁴⁸ and pyridines and pyrimidines derivatives.⁴⁹

Our research group recently reported the use of Oxone^® to generate electrophilic species of selenium evidencing its application in selenylation reactions.^50-54 As an example, we reported an alternative metal-free methodology for the synthesis of diorganyl selenides and tellurides mediated by Oxone^®.⁵¹ Other examples include the selenomethoxylation of inactivated alkenes,⁵² the synthesis of 2-organoselanyl-naphthalenes under ultrasonic irradiation,⁵³ the selective synthesis of 5-arylselanyl-imidazo[2,1-b]thiazoles, 3-arylselanyl-imidazo[1,2-a]pyridines and 4-arylselanyl-1H-pyrazoles derivatives via direct selenylation C-Se coupling reaction mediated by Oxone^®.⁵⁴

Thus, based on literature,^38-42 our recent report using Oxone^® in selenylation reactions^50-54 and due to our continuous interest in the preparation of nitrogen-functionalized organoselenium compounds,^55-59 we describe herein our results on the synthesis of a range of 4-(organylselanyl)-1H-pyrazoles 4 by Oxone^®-mediated oxidative multicomponent reaction of hydrazines 1, 1,3-diketones 2 and diorganyl diselenides 3 (Scheme 3).

Scheme 3
General scheme for synthesis of 1-aryl-4-(organylselanyl)-1H-pyrazoles.

Results and Discussion

Based in our previous results,⁴¹ the reaction was peformed using phenylhydrazine 1a (0.250 mmol), 2,4-pentanedione 2a (0.250 mmol) and diphenyl diselenide 3a (0.125 mmol) in CH₃CN (1.0 mL). After that we added Oxone^® (0.500 mmol) keeping the reaction mixture under stirring at 50 °C for 24.0 h and air atmosphere. The desired product 3,5-dimethyl-1-phenyl-1H-pyrazole 4a was obtained in 50% yield (Table 1, entry 1).

Table 1
Reaction conditions optimization^a

entry	3a / mmol	Oxone® / mmol	Temperature / ºC	time / h	Solvent	Yieldb4a / %
1	0.125	0.500	50	24.0	CH3CN	50
2	0.188	0.500	50	24.0	CH3CN	85
3c	0.250	0.500	50	1.0	CH3CN	97
4	0.250	0.250	50	1.0	CH3CN	54
5	0.250	0.500	25	2.0	CH3CN	68
6	0.250	0.500	reflux	0.5	CH3CN	85
7c	0.250	0.500	50	0.5	CH3COOH	98
8	0.250	0.500	50	1.0	EtOH	83
9	0.250	0.500	50	24.0	H2O	40
10	0.250	0.500	50	2.0	PEG-400	71

• ^a
  Reactions were performed with substrates 1a (0.250 mmol), 2a (0.250 mmol), 3a and Oxone^® in 1.0 mL of solvent in the open atmosphere;
• ^b
  yields are given for isolated products;
• ^c
  the excess of 3a was recovered by column chromatography.

Aiming to improve the yield of the 4a, we examined the influence of different solvents, temperature, reaction time, amount of 3a and Oxone^®, as depicted in Table 1, entries 2 to 10. Thus, when the reaction was performed with 0.188 and 0.250 mmol of the 3a an increase in the yield of the product 4a was observed with reduction of the reaction time (Table 1, entries 2 and 3). However, a decrease in the yield of product 4a was observed when the amount of the Oxone^® was reduced to 0.250 mmol (Table 1, entry 4). This result is probably due to the incomplete oxidation of diphenyl diselenide 3a in the presence of Oxone^®. Next, the reaction was performed at 25 °C and reflux temperature and a decrease in the yield of product 4a was observed (Table 1, entries 5 and 6).

Next, the reaction was performed using different solvents (Table 1, entries 7 to 10). When acetic acid was used as a solvent the yield was increased to 98% and the reaction time was reduced to only 0.5 h (Table 1, entry 7). However, when it was used other solvents including EtOH, H₂O or PEG-400, lower yields of 4a (Table 1, entries 8, 9 and 10 vs. 7) was obtained.

In order to verify the scope and limitations of this protocol, the generality of our method was explored by extending the optimized reaction conditions (Table 1, entry 7) to other substituted reagents, and the results are shown in Table 2. Firstly, 1,3-diketones 2a-c were reacted with phenylhydrazine 1a and diphenyl diselenide 3a (Table 2, entries 1 to 3). Thus, when the reactions were performed with 3,5-heptanedione 2b the desired product 4b was obtained in 90% yield (Table 2, entry 2). When unsymmetrical 1-phenyl-1,3-butanedione 2c was used, two regioisomers were obtained providing the corresponding 4-selanylpyrazoles 4c and 4c’ in the ratio (96:4) determined by gas chromatography mass spectrometry (GC-MS) analysis in 89% yield (Table 2, entry 3). We believe that steric hinderance of 2c associated to the conjugative effect of aromatic ring can contribute to stabilize the enol tautomer increasing the regioselectivity of this cyclization towards the formation of product 4c as major isomer.

Table 2
Reaction scope for the synthesis of 4-organylselanylpyrazoles 4a-l^a

entry	Hydrazine 1	1,3-Diketone 2	Diselenide 3	Product 4	Yieldb / %
1					98
2					90
3					89c
4					69d
5					44d
6					75d
7					77
8					84
9					81
10					90
11					90
12					58

• ^a
  Reactions were performed with substrates 1a-d (0.250 mmol), 2a-c (0.250 mmol), 3a-g (0.250 mmol), Oxone^® (0.500 mmol) in acetic acid (1.0 mL) as solvent at 50 ºC in air atmosphere for 0.5 h;
• ^b
  yields are given for isolated products;
• ^c
  the mixture of regioisomers 4c/4c' (96:4) was obtained and determined by GC-MS analysis;
• ^d
  the reaction was carried for 1.0 h.

Subsequently, the reactions were performed with arylhydrazines 1b and 1c containing electron-donating group (EDG) and electron-withdrawing groups (EWG), to give the corresponding 4-arylselanylpyrazoles 4d and 4e in 69 and 44% yields, respectively (Table 2, entries 4 and 5). These results reveal that the reactions are sensitive to the electronic effect of the aromatic ring in the arylhydrazine. On the other hand, when hydrazine hydrochloride 1d was used as a starting substrate, the desired product 4f was obtained in 75% yield (Table 2, entry 6).

Furthermore, varying substituted diaryl diselenides 3 was evaluated to determine the influence of electron-donating (-Me, -OMe) and electron-withdrawing groups (-Cl, -F) in this reaction. The corresponding 4-selanylpyrazoles 4g-j were obtained in good yields (Table 2, entries 7-10). The reaction of substituted diaryl diselenides is well tolerated and the results reveal that yields are not sensitive to the electronic effects in the diaryl diselenides containing EDG (3b and 3c) and EWG (3d and 3e).

The reaction also worked well with dibutyl diselenide 3f, and the corresponding 4-butylselanyl-3,5-dimethyl-1-phenyl-1H-pyrazole 4k was obtained in good yield (Table 2, entry 11). Moreover, 2,2’-dipyridyl diselenide 3g also gives the desired 2-[(3,5-dimethyl-1-phenyl-1H-pyrazol-4-yl)selanyl]pyridine 4l in a moderate yield of 58% (Table 2, entry 12). In this case the respective pyrazole containig a selanyl-pyridine group showed a decrease in yield probably due to the decrease of the electrophilic character of the selenium species, reducing their reactivity, caused by the conjugation of the electrons of the pyridine ring.

To extend the reaction scope, the multicomponent reaction (MCR) was evaluated in presence of (E)-chalcone 5 using optimized reaction conditions. Under this reaction condition the desired 1,3,5-triaryl-4-(phenylselanyl)-1H-pyrazoles 4m was obtained in only 15% yield. Based on this result, a mixture of phenylhydrazine 2a and chalcone 5 in acetic acid was stirred at reflux temperature for 2.0 h to afford in situ the pyrazolyl nucleus A. After this, diphenyl diselenide 3a and Oxone^® were added at 50 °C for 0.5 h and the desired product 1,3,5-triphenyl-4-(phenylselanyl)-1H-pyrazoles 4m was obtained in 81% yield (Scheme 4).

Scheme 4
General scheme for synthesis of 1,3,5-triphenyl-4-(phenylselanyl)-1H-pyrazole, 4m.

Conclusions

In summary, we developed an efficient method for the synthesis of 4-organylselanylpyrazoles through the multicomponent reaction of 1,3-diketones, hydrazine and diaryl selenides. The reaction was Oxone^®-promoted in acetic acid at 50 °C under air atmosphere and in short reaction times, a range of substituted 4-organylselanylpyrazoles was obtained in good to excellent yields.

Experimental

General information

The reactions were monitored by thin layer chromatography (TLC) carried out on Merck silica gel (60 F₂₅₄) by using UV light as visualization agent and the mixture between of vanillin 5% and of H₂SO₄ 10% under heating conditions as developing agents. Merck silica gel (particle size 0.040-0.063 mm) was used for flash chromatography. Hydrogen nuclear magnetic resonance spectra (¹H NMR) were obtained on Bruker Ascend 400 spectrometer at 400 MHz. The spectra were recorded in CDCl₃ solutions. The chemical shifts are reported in ppm, referenced to tetramethylsilane (TMS) as the internal reference. Coupling constants (J) are reported in hertz. Abbreviations to denote the multiplicity of a particular signal are s (singlet), d (doublet), dd (doublet of doublets), ddd (doublet of doublet of doublets), dt (doublet of triplets), t (triplet), q (quartet), quint (quintet), sext (sextet), and m (multiplet). Carbon-13 nuclear magnetic resonance spectra (¹³C NMR) were obtained on Bruker Ascend 400 spectrometer at 100 MHz. The chemical shifts are reported in ppm, referenced to the solvent peak of CDCl₃. Low-resolution mass spectra were obtained with a Shimadzu GC-MS-QP2010 mass spectrometer. The high-resolution electrospray ionization mass spectrometry (QTOF) analysis were performed on a Bruker Daltonics micrOTOF-Q II instrument in operating positive mode. The samples were solubilized in high-performance liquid chromatography (HPLC)-grade acetonitrile and injected into the atmospheric pressure chemical ionization (APCI) source by means of a syringe pump at a flow rate of 5.0 µL min^-1. The follow instrument parameters were applied: capillary and cone voltages were set to +3500 and -500 V, respectively, with a desolvation temperature of 180 ºC. For data acquisition and processing and isotopes simulations, Compass 1.3 for micrOTOF-Q II software (Bruker Daltonics) was used. Melting point (mp) values were measured in a Marte PFD III instrument with a 0.1 ºC precision.

Synthesis

General procedure for synthesis of 4-arylselanyl-1H-pyrazoles (4a-l)

In a reaction tube of 10.0 mL it was added a mixture of the respectives hydrazines 1a-d (0.25 mmol), 1,3-diketones 2a-c (0.25 mmol), diselenides 3a-g (0.25 mmol) and Oxone^® 0.5 mmol in CH₃COOH (1.0 mL). The mixture was stirred at 50 °C for the time indicated in Table 2. The aqueous sodium bicarbonate solution 5% (10.0 mL) and ethyl acetate (15.0 mL) were added. The organic phase was washed with water (2 × 10.0 mL), separated, dried over MgSO₄, and the solvent was evaporated under reduced pressure. The product was isolated by column chromatography using hexane/ethyl acetate (98/2% v/v) as eluent.

3,5-Dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazole (4a)^40,41

Yield: 0.080 g (98%); orange solid; mp 82-84 °C; ¹H NMR (400 MHz, CDCl₃) ẟ 2.33 (s, 3H, CH₃), 2.37 (s, 3H, CH₃), 7.11-7.16 (m, 1H, Ar-H), 7.19-7.20 (m, 4H, Ar-H), 7.34-7.40 (m, 1H, Ar-H), 7.44-7.48 (m, 4H, Ar-H);¹³C NMR (100 MHz, CDCl₃) ẟ 12.4, 12.9, 102.5, 124.6, 125.7, 127.7, 128.2, 129.0, 129.1, 132.9, 139.7, 144.0, 153.2; MS (relative intensity / %) m/z: 77 (96.2), 118 (55.0), 157 (3.8), 171 (5.2), 248 (100.0), 328 (75.4).

3,5-Diethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazole (4b)^40,41

Yield: 0.080 g (90%); orange oil; ¹H NMR (400 MHz, CDCl₃) ẟ 1.00 (t, 3H, J 7.6 Hz, CH₃), 1.23 (t, 3H, J 7.6 Hz, CH₃), 2.72 (q, 2H, J 7.6 Hz, CH₂), 2.78 (q, 2H, J 7.6 Hz, CH₂), 7.10-7.15 (m, 1H, Ar-H), 7.19-7.20 (m, 4H, Ar-H), 7.37-7.42 (m, 1H, Ar-H), 7.47-4.48 (m, 4H, Ar-H); ¹³C NMR (100 MHz, CDCl₃) ẟ 13.7, 13.9, 19.1, 20.8, 100.3, 125.3, 125.6, 128.0, 129.0, 129.1, 133.6, 140.0, 149.7, 158.3; MS (relative intensity / %) m/z: 77 (48.4), 132 (17.0), 157 (2.1), 199 (3.2), 275 (100.0), 356 (36.8).

3-Methyl-1,5-diphenyl-4-(phenylselanyl)-1H-pyrazole (4c)^40,41

Yield: 0.087 g (89%); beige solid; mp 68-69 °C; ¹H NMR (400 MHz, CDCl₃) ẟ 2.39 (s, 3H, CH₃), 7.11-7.22 (m, 7H, Ar-H), 7.23-7.32 (m, 8H, Ar-H);¹³C NMR (100 MHz, CDCl₃) ẟ 13.0, 103.5, 124.8, 125.8, 127.2, 128.2, 128.5, 128.7, 128.8, 129.1, 129.9, 130.1, 133.3, 139.9, 147.0, 154.0; MS (relative intensity / %) m/z: 77 (71.6), 157 (0.9), 180 (18.8), 233 (5.3), 310 (100.0), 390 (69.5).

1-(2,4-Dimethylphenyl)-3,5-dimethyl-4-phenylselanyl-1H-pyrazole (4d)

Yield: 0.061 g (69%); yellowish solid; mp 84-86 °C; ¹H NMR (400 MHz, CDCl₃) ẟ 2.03 (s, 3H, Ar-CH₃), 2.11 (s, 3H, Ar-CH₃), 2.31 (s, 3H, CH₃), 2.38 (s, 3H, CH₃), 7.07-7.22 (m, 8H, Ar-H); ¹³C NMR (100 MHz, CDCl₃) ẟ 11.3, 12.9, 17.1, 21.1, 100.4, 125.6, 127.2, 127.4, 128.0, 129.1, 131.5, 133.3, 135.5, 136.2, 139.2, 145.2, 152.7; MS (relative intensity / %) m/z: 77 (45.0), 105 (28.4), 118 (4.5), 157 (12.9), 199 (11.0), 275 (66.4), 356 (100.0). HRMS (APCI-QTOF) m/z, calcd. for C₁₉H₂₀N₂Se [M + H]^­+: 357.0870, found: 357.0865.

1-(2,4-Dichlorophenyl)-3,5-dimethyl-4-phenylselanyl-1H-pyrazole (4e)

Yield: 0.044 g (44%); orange solid; mp 80-82 °C; ¹H NMR (400 MHz, CDCl₃) ẟ 2.17 (s, 3H, CH₃), 2.31 (s, 3H, CH₃), 7.12-7.23 (m, 5H, Ar-H), 7.39 (d, 2H, J 1.2 Hz, Ar-H), 7.56 (t, 1H, J 1.2 Hz, Ar-H);¹³C NMR (100 MHz, CDCl₃) ẟ 11.3, 13.0, 101.7, 125.7, 128.0, 128.1, 129.2, 130.1, 130.4, 132.8, 133.3, 135.9, 136.1, 146.2, 154.0; MS (relative intensity / %) m/z: 77 (24.7), 118 (4.4), 144 (57.8), 157 (5.7), 239 (5.7), 361 (100.0), 396 (75.4); HRMS (APCI-QTOF) m/z, calcd. for C₁₇H₁₄Cl₂N₂Se [M + H]⁺: 396.9778, found: 396.9767.

3,5-Dimethyl-4-(phenylselanyl)-1H-pyrazole (4f)⁴¹

Yield: 0.047 g (75%); white solid; mp 104-105 °C; ¹H NMR (400 MHz, CDCl₃) ẟ 2.25 (s, 6H, 2CH₃), 7.03-7.12 (m, 5H, Ar-H);¹³C NMR (100 MHz, CDCl₃) ẟ 11.9, 100.1, 125.6, 128.2, 129.1, 133.1, 149.0; MS (relative intensity / %) m/z: 77 (16.3), 95 (13.2), 118 (1.6), 157 (10.6), 172 (100.0), 252 (58.9).

3,5-Dimethyl-1-phenyl-4-(4-tolylselanyl)-1H-pyrazole (4g)^40,41

Yield: 0.066 g (77%); slightly orange solid; mp 96-97 °C; ¹H NMR (400 MHz, CDCl₃) ẟ 2.27 (s, 3H, Ar-CH₃), 2.33 (s, 3H, CH₃), 2.38 (s, 3H, CH₃), 7.01-7.03 (m, 2H, Ar-H), 7.10-7.13 (m, 2H, Ar-H), 7.34-7.40 (m, 1H, Ar-H), 7.44-7.47 (m, 4H, Ar-H); ¹³C NMR (100 MHz, CDCl₃) ẟ 12.4, 12.9, 20.9, 103.0, 124.7, 127.6, 128.7, 128.97, 129.04, 129.9, 135.6, 139.9, 143.8, 153.1; MS (relative intensity / %) m/z: 77 (55.1), 118 (32.1), 170 (3.9), 171 (5.7), 262 (100.0), 342 (46.7).

4-[(4-Methoxyphenyl)selanyl]-3,5-dimethyl-1-phenyl-1H-pyrazole (4h)^40,41

Yield: 0.075 g (84%); red oil; ¹H NMR (400 MHz, CDCl₃) d 2.34 (s, 3H, CH₃), 2.39 (s, 3H, CH₃), 3.75 (s, 3H, OCH₃), 6.76-6.80 (m, 2H, Ar-H), 7.19-7.22 (m, 2H, Ar-H), 7.34-7.38 (m, 1H, Ar-H), 7.43-7.48 (m, 4H, Ar-H); ¹³C NMR (100 MHz, CDCl₃) ẟ 12.4, 12.9, 55.2, 103.9, 114.9, 122.6, 124.7, 127.6, 129.0, 131.1, 139.9, 143.6, 152.9, 158.5; MS (relative intensity / %) m/z: 77 (39.7), 118 (22.1), 171 (2.0), 187 (1.5), 278 (100.0), 358 (32.2).

4-[(4-Chlorophenyl)selanyl]-3,5-dimethyl-1-phenyl-1H-pyrazole (4i)^40,41

Yield: 0.073 g (81%); yellowish solid; mp 124-125 °C; ¹H NMR (400 MHz, CDCl₃) ẟ 2.32 (s, 3H, CH₃), 2.37 (s, 3H, CH₃), 7.10-7.13 (m, 2H, Ar-H), 7.15-7.18 (m, 2H, Ar-H), 7.35-7.42 (m, 1H, Ar-H), 7.45-7.50 (m, 4H, Ar-H); ¹³C NMR (100 MHz, CDCl₃) ẟ 12.4, 12.8, 102.3, 124.7, 127.8, 129.1, 129.2, 129.6, 131.2, 131.8, 139.7, 144.0, 153.1; MS (relative intensity / %) m/z: 77 (100.0), 118 (59.5), 171 (3.9), 191 (2.3), 282 (83.9), 362 (66.3).

4-[(4-Fluorophenyl)selanyl]-3,5-dimethyl-1-phenyl-1H-pyrazole (4j)

Yield: 0.078 g (90%); orange oil; ¹H NMR (400 MHz, CDCl₃) ẟ 2.33 (s, 3H, CH₃), 2.38 (s, 3H, CH₃), 6.89-6.95 (m, 2H, Ar-H), 7.16-7.21 (m, 2H, Ar-H), 7.36-7.40 (m, 1H, Ar-H), 7.44-7.50 (m, 4H, Ar-H); ¹³C NMR (100 MHz, CDCl₃) ẟ 12.4, 12.9, 103.1, 116.2 (d, J 21.7 Hz), 124.7, 127.2 (d, J 3.4 Hz), 127.8, 129.1, 130.5 (d, J 7.4 Hz), 139.8, 143.9, 153.0, 161.6 (d, J 243.6 Hz); MS (relative intensity / %) m/z: 77 (94.1), 118 (55.3), 171 (4.7), 175 (3.6), 266 (100.0), 346 (74.7); HRMS (APCI-QTOF) m/z, calcd. for C₁₇H₁₅FN₂Se [M + H]^­+: 347.0463, found: 347.0459.

4-(Butylselanyl)-3,5-dimethyl-1-phenyl-1H-pyrazole (4k)⁴¹

Yield: 0.069 g (90%); yellowish oil; ¹H NMR (400 MHz, CDCl₃) ẟ 0.90 (t, 3H, J 7.5 Hz, CH₃), 1.41 (sext, 2H, J 7.5 Hz, CH₂), 1.58 (quint, 2H, J 7.5 Hz, CH₂), 2.39 (s, 3H, CH₃), 2.40 (s, 3H, CH₃), 2.58 (t, 2H, J 7.5 Hz, CH₂), 7.33-7.37 (m, 1H, Ar-H), 7.41-7.47 (m, 4H, Ar-H); ¹³C NMR (100 MHz, CDCl₃) ẟ 12.5, 13.0, 13.5, 22.7, 28.3, 32.3, 103.2, 124.6, 127.4, 129.0, 140.0, 143.2, 152.8; MS (relative intensity / %) m/z: 57 (6.1), 77 (72.3), 118 (75.4), 171 (100.0), 251 (24.3), 308 (43.9).

2-[(3,5-Dimethyl-1-phenyl-1H-pyrazol-4-yl)selanyl]pyridine (4l)

Yield: 0.048 g (58%); colorless oil; ¹H NMR (400 MHz, CDCl₃) ẟ 2.35 (s, 3H, CH₃), 2.40 (s, 3H, CH₃), 6.88 (dt, 1H, J 8.0, 0.9 Hz, Ar-H), 7.02 (ddd, 1H, J 7.4, 4.8, 0.9 Hz, Ar-H), 7.37-7.44 (m, 2H, Ar-H), 7.48-7.50 (m, 4H, Ar-H), 8.43 (ddd, 1H, J 4.8, 1.9, 0.9 Hz, Ar-H); ¹³C NMR (100 MHz, CDCl₃) ẟ 12.4, 12.9, 102.2, 120.0, 121.9, 124.7, 127.8, 129.1, 136.6, 139.8, 144.3, 149.9, 153.2, 158.7; MS (relative intensity / %) m/z: 77 (53.5), 118 (31.9), 156 (11.0), 171 (100.0), 248 (54.9), 329 (31.5); HRMS (APCI-QTOF) m/z calcd. for C₁₆H₁₅N₃Se [M + H]^­+: 330.0509, found: 330.0520.

General procedure for synthesis of 1,3,5-triphenyl-4-(phenylselanyl)-1H-pyrazole (4m)

In a reaction flask of 25.0 mL has added a mixture of the chalcone 5 (0.25 mmol) and phenylhydrazine 1a (0.25 mmol) in CH₃COOH (1.0 mL). The mixture was stirred for 2 h under reflux, then the temperature was lowered to 50 °C and the diphenyl diselenide 3a (0.25 mmol) and Oxone^® (0.5 mmol) were added. The mixture was stirred for 0.5 h. The aqueous sodium bicarbonate solution 5% (10.0 mL) and ethyl acetate (15.0 mL) were added. The organic phase was washed with water (2 × 10.0 mL), separated, dried over MgSO₄, and the solvent was evaporated under reduced pressure. The product was isolated by column chromatography using hexane/ethyl acetate (98/2% v/v) as eluent.

1,3,5-Triphenyl-4-(phenylselanyl)-1H-pyrazole (4m)

Yield: 0.092 g (81%); yellowish solid; mp 127-129 °C; ¹H NMR (400 MHz, CDCl₃) ẟ 7.09-7.22 (m, 7H, Ar-H), 7.23-7.39 (m, 11H, Ar-H), 7.96-7.99 (m, 2H, Ar-H); ¹³C NMR (100 MHz, CDCl₃) ẟ 101.7, 124.9, 125.8, 127.4, 128.1, 128.2, 128.3, 128.4, 128.6, 128.78, 128.82, 129.1, 129.9, 130.3, 132.8, 134.1, 139.9, 148.4, 155.0; MS (relative intensity / %) m/z: 157 (0.9), 180 (49.7), 372 (100.0), 452 (60.2).

Supplementary Information

Supplementary information is available free of charge at http://jbcs.sbq.org.br as PDF file.

Acknowledgments

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil (CAPES), finance code 001. We thank CNPq, CAPES, FAPERGS (PqG 17/2551-0000987-8) for the financial support.

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Publication Dates

• Publication in this collection
  21 Oct 2019
• Date of issue
  Oct 2019

History

• Received
  31 Jan 2019
• Accepted
  15 May 2019