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. 2026 Jul 17;91(30):10351–10364. doi: 10.1021/acs.joc.6c00605

Blue Light-Mediated Multicomponent Synthesis of 5‑Amino-4-chalcogenyl-1H-pyrazoles

Pâmella Cordeiro †, João Pedro S S C Thomaz ‡, Matheus G Theodorio ‡, Thiago J Peglow ‡, Thiago Barcellos §, Antonio L Braga †, Vanessa Nascimento ‡,*
PMCID: PMC13435315  PMID: 42466891

Abstract

Visible-light-mediated multicomponent reactions offer a simple and efficient approach for constructing functionalized heterocycles. Herein, we report a photocatalyst-free, iodine-mediated multicomponent protocol for the synthesis of 5-amino-4-chalcogenyl-1H-pyrazoles from 3-oxo-3-phenylpropanenitriles, arylhydrazines, and diorganyl dichalcogenides under blue-LED irradiation. The transformation proceeds without transition metals, external oxidants, or additives. Notably, the same optimized reaction conditions enable access to both selenium- and sulfur-containing derivatives without reoptimization, demonstrating the robustness and generality of the methodology. The protocol exhibits a broad substrate scope, enabling the preparation of more than 30 structurally diverse examples and tolerating electron-donating and -withdrawing substituents on both the dichalcogenide and hydrazine partners. Selenium derivatives were obtained in excellent yields, while disulfide analogues were also formed in high yields (up to 98). The synthetic utility was further demonstrated through gram-scale reactions, crossover experiments, and downstream derivatization via the Clauson-Kaas reaction. Control and radical-trapping experiments support a visible light-induced radical pathway, where photoirradiation is responsible for radical generation, enabling the formation of chalcogen-centered species. Overall, this study provides a straightforward strategy for the synthesis of chalcogen-functionalized pyrazoles under mild, metal-free conditions.

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Introduction

Pyrazole derivatives represent a class of heterocycles of great interest due to their wide range of applications in different areas of chemistry and materials science. , Structurally, pyrazoles feature a five-membered aromatic ring containing two vicinal nitrogen atoms with distinct electronic characters, which govern tautomerism, hydrogen-bonding behavior, and metal-coordination properties. In addition to their well-established pharmacological relevance, associated with anti-inflammatory, anticancer, and antimicrobial activities, these structures have increasingly attracted attention as building blocks in organic synthesis, serving as precursors for more complex heteroaromatic systems (Figure ). − From an applied perspective, pyrazole derivatives are widely exploited not only as ligands in homogeneous catalysis and components of optical and electrochemical sensors but also as key motifs in commercial agrochemicals, including fungicides, herbicides, and insecticides. This versatility arises from the aromatic nature of the heterocyclic core combined with the possibility of site-selective functionalization, which allows for fine modulation of electronic, photophysical, and coordination properties. In particular, aminopyrazoles constitute an important subclass, widely explored as key building blocks in medicinal chemistry and materials science because of their rich functionalization patterns and diverse biological activities. ,

1.

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Examples of pyrazole-containing compounds and their applications.

The functionalization of heterocyclic scaffolds with chalcogen elements has become an effective approach to modulate molecular structure and properties. − Because of their high polarizability and ability to engage in directional noncovalent interactions, such as chalcogen bonding, sulfur, selenium, and tellurium play a central role in controlling reactivity and molecular recognition. − In synthetic chemistry, organochalcogen compounds are well-established as organocatalysts, intermediates, and reagents in selective transformations. As observed for pyrazole derivatives, the deliberate introduction of chalcogen atoms into heterocyclic architectures affords highly tunable molecular systems, reinforcing their value in the development of advanced functional materials and technological relevance. −

Given this broad spectrum of applications, increasing attention has been directed toward the chalcogen functionalization of pyrazole frameworks, especially the synthesis of 4-arylselenyl-1H-pyrazoles. Reported methods include reactions with selenium electrophiles, transition-metal catalysis, selenium halides, and a visible-light protocol employing Rose Bengal as a photocatalyst (Scheme a), − which, although efficient, relies on additional chemical inputs. However, existing methodologies are largely limited to selenium or sulfur individually. Sulfur derivatives usually require harsh thermal conditions, while visible-light approaches remain restricted to selenium and still depend on photocatalysts. − These limitations contrast with green chemistry principles and the United Nations Sustainable Development Goals (SDGs), notably those related to responsible consumption and production (SDG 12), industrial, innovation and infrastructure (SDG 9), and reduction of environmental impact. , Consequently, the development of broader and more sustainable methodologies for the synthesis of chalcogen-functionalized pyrazoles remains highly desirable.

1. Synthesis of 4-Arylchacogenyl-1H-pyrazoles; (a) Previous Works; (b) This Work.

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In this context, multicomponent reactions emerge as powerful alternatives, offering significant advantages in organic synthesis, such as atom economy, operational simplicity, structural diversity, and reduced waste generation. − The combination of multicomponent strategies with visible-light irradiation has also proven effective; however, the most desirable approach avoids the use of photocatalysts, which, although efficient, present drawbacks related to cost, potential toxicity, and challenges in removal or recycling, ultimately diminishing the overall greenness of the process. − Building upon these principles, in this work, we report a multicomponent approach using visible light, photocatalyst-free, for the synthesis of chalcogen-containing pyrazoles, namely 4-arylselanyl-1H-pyrazoles as well as their sulfur-containing analogues. The transformation proceeds in the presence of catalytic iodine, without the need for additional additives, and employs ethyl acetate as a greener solvent, highlighting its potential as an environmentally friendly and operationally simple method (Scheme b).

Results and Discussion

The initial reaction conditions were selected based on previously reported conventional chalcogenation protocols employing molecular iodine as a radical promoter/oxidative mediator in combination with organic photocatalysts. Thus, a mixture of 1 (0.5 mmol), 2a (0.7 mmol), and 3a (0.5 mmol) was irradiated with a 50 W blue LED in acetonitrile, in the presence of iodine (50 mol %) and Eosin Y. After 12 h, the desired product (4a) was obtained in 72% yield (Table , entry 1), while Rose Bengal provided a slightly higher yield of 76% (Table , entry 2). Encouraged by these results, we next investigated whether the reaction could proceed efficiently in the absence of light by evaluating different additives under thermal conditions (Table , entries 3–7). While most additives did not significantly improve the yield, FeCl3 proved to be particularly effective, affording the target compound in 84% yield under light-free conditions. Given the promising performance of FeCl3 alone, we then examined whether a combined system (photocatalyst + FeCl3 under irradiation) could further enhance the reaction efficiency. However, no synergistic effect was observed: the combination of Eosin Y and FeCl3 resulted in a decreased yield (57%, Table , entry 8), whereas Rose Bengal with FeCl3 furnished a 75% yield (Table , entry 9). These findings demonstrate that using FeCl3 as a single additive under light-free conditions is more efficient than using photocatalytic systems or combined approaches. Importantly, this outcome is advantageous from a green chemistry perspective as it eliminates the need for continuous light irradiation and avoids the use of relatively expensive organic photocatalysts, thereby simplifying the protocol and improving its economic and operational sustainability. Reducing the FeCl3 loading improved the yield to 90% (Table , entry 10), and omitting it completely further increased the yield to 92% (Table , entry 11), simplifying the process.

1. Optimization of Reaction Conditions ,

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# Visible light Iodine source (50 mol %) Photocatalyst Aditive Solvent Time (h) Yield (%)
1 Blue LED 50W I2 Eosin Y - CH3CN 12 72
2 Blue LED 50W I2 Rose Bengal - CH3CN 12 76
3 Blue LED 50W I2 - InCl3 CH3CN 12 19
4 Blue LED 50W I2 - SnCl4 CH3CN 12 N.R.
5 Blue LED 50W I2 - SnCl2.H2O CH3CN 12 22
6 Blue LED 50W I2 - BF3OEt2 CH3CN 12 20
7 Blue LED 50W I2 - FeCl3 CH3CN 12 84
8 Blue LED 50W I2 Eosin Y FeCl3 CH3CN 12 57
9 Blue LED 50W I2 Rose Bengal FeCl3 CH3CN 12 75
10 Blue LED 50W I2 - FeCl3 CH3CN 12 90
11 Blue LED 50W I2 - - CH3CN 12 92
12 Blue LED 50W I2 - - CH3CN 24 37
13 Blue LED 50W I2 - - CH3CN 6 43
14 Green LED 50W I2 - - CH3CN 12 37
15 Blue LED 100W I2 - - CH3CN 12 58
16 Blue LED 50W KIO3 - - CH3CN 12 N.R.
17 Blue LED 50W others - - CH3CN 12 Traces
18 Blue LED 50W NIS - - CH3CN 12 44
19 Blue LED 50W I2 - - CH3CN 12 58
20 Blue LED 50W - - - CH3CN 12 N.R.
21 Blue LED 50W I2 - - AcOEt 12 96
22 Blue LED 50W I2 - - others 12 Low
23 - I2 - - AcOEt 12 45
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a

In a round-bottomed tube, 3-oxo-3-phenylpropanenitrile 1 (0.5 mmol), hydrazine 2a (0.7 mmol), diphenyl diselenide 3a (0.5 mmol), and solvent (3.0 mL) were added.

b

Yields obtained after column chromatography.

c

Reaction performed using FeCl3 (5 mol %).

d

Reaction performed using I2 (25 mol %).

e

In the absence of light (in the dark).

f

Using KIO4, CuI, or KI, only trace amounts of the product were observed

g

Using hexane (N.R.), toluene (52%), EtOH (84%), or THF (44%), lower yields were observed; N.R. = no reaction.

Next, we examined the effect of the reaction time. Interestingly, increasing the irradiation period to 24 h or reducing it to 6 h resulted in lower yields of 37% and 43%, respectively (Table , entries 12 and 13), indicating that 12 h is the optimal reaction time. Subsequently, the influence of the light source was also assessed. Using a green LED instead of a blue LED resulted in only a 37% yield (Table , entry 14), while increasing the power of the blue LED to 100 W also proved detrimental, giving a 58% yield (Table , entry 15). To investigate the role of iodine in the reaction, alternative iodine sources were tested (Table , entries 16–19), but none outperformed molecular iodine, which remained the most effective under the studied conditions. Moreover, reducing the loading of I2 from 50 mol % to 25 mol % decreased the yield to 58% (Table , entry 19). No reaction occurred in the absence of I2, which highlights its crucial role in the process.

Solvents such as hexane, toluene, ethanol, THF, acetonitrile, and ethyl acetate were screened to evaluate the solvent effect (Table , entry 22). Hexane completely suppressed the reaction, whereas toluene, ethanol, and THF afforded moderate yields (52%, 84%, and 44%, respectively). Acetonitrile, initially employed, provided a good yield (92%); however, ethyl acetate proved to be the most efficient solvent, delivering the product in a 96% yield (Table , entry 21). Under dark conditions, the reaction proceeded with a reduced yield of 45%. Thus, the optimal conditions correspond to those described in Table , entry 23, employing I2 (50 mol %) in ethyl acetate under blue LED irradiation for 12 h.

The generality of the optimized protocol was then evaluated using a series of substituted diselenides bearing electron-donating (EDG) and electron-withdrawing groups (EWG), as well as alkyl and heteroaromatic substituents (Scheme ). The mesityl-substituted derivative (4b) was obtained in good yield (67%), whereas the p-methyl (4c) and p-methoxy (4d) substituent analogues showed no reactivity under the standard conditions. Notably, the naphthyl derivative (4e) furnished the desired product in excellent yield (80%), while the thiophene-substituted derivative (4f) afforded a moderate yield (45%). To further investigate the substrate scope, an alkyl-substituted diselenide was also evaluated, and the corresponding product was formed (4g) in 32% yield. Among the electron-withdrawing substituents, the p-chloro derivative (4h) performed remarkably well, yielding the product at 83%. The para-fluoro (4i) and trifluoromethyl (4j) analogues were also compatible, providing good yields of 65% and 56%, respectively. Furthermore, the scalability of the protocol was demonstrated by conducting the reaction on a 3.0 mmol scale under the optimized conditions, affording product 4a in 91% yield after 12 h.

2. Substrate Scopes for 5-Amino-4-(arylselanyl)-1H-pyrazoles Using Different Diselenides,

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a In a round-bottomed tube, 3-oxo-3-phenylpropanenitrile 1 (0.5 mmol), hydrazine 2a (0.7 mmol), diselenide 3 (0.5 mmol), and solvent (3.0 mL) were added.

b Yields were obtained after column chromatography.

Encouraged by the excellent results achieved in the formation of selenium-functionalized products, we further explored the adaptability of the visible light-mediated chalcogen cyclization reaction using diorganyl disulfides and diorganyl ditellurides as substrates under the previously optimized reaction conditions (Scheme ).

3. Substrate Scopes for 5-Amino-4-(arylselanyl)-1H-pyrazoles Using Different Disulfides,

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a In a round-bottomed tube, 3-oxo-3-phenylpropanenitrile 1 (0.5 mmol), hydrazine 2a (0.7 mmol), dichalcogenides 5 (0.5 mmol), and solvent (3.0 mL) were added.

b Yields obtained after column chromatography.

Notably, although the tellurium analogue (6h) was unreactive under the optimized conditions, the same protocol proved to be directly applicable to disulfides without any further modification of the reaction parameters. This operational simplicity highlights the robustness and generality of the method, enabling the selective functionalization of different chalcogen classes under identical conditions. In this series, excellent results were obtained, which is consistent with previous reports describing the higher reactivity of disulfides in related chalcogen transfer processes. Accordingly, the phenyl derivative afforded an outstanding 98% yield (6a). EDGs were generally more favorable, as demonstrated by the p-methyl (83%, 6b), m-methyl (76%, 6c), and o-methyl (50%, 6d) derivatives. In contrast, EWGs resulted in lower efficiencies, with the p-fluoro (50%, 6e) and p-chloro (60%, 6f) analogues. Furthermore, a nonaromatic substrate (cyclohexyl, 6g) was evaluated; however, no reaction was observed under the developed conditions, suggesting the importance of an aromatic group in the nitrile component.

Building upon the excellent performance of the visible-light-mediated chalcogen cyclization, we were encouraged by the robustness of the methodology. This prompted us to expand the compound library by exploring a broader set of hydrazine derivatives (Scheme ), bearing both EDG and EWG substituents and applying selenium- and sulfur-containing precursors. In the case of p-methyl-substituted hydrazines, moderate reactivity was observed, giving a 30% yield for the selenium (7a) derivative and a 45% yield for the sulfur analogue (8a). For halogenated systems, the p-bromo substrate showed an opposite trend, with selenium performing significantly better (7b, 84%) compared to sulfur (8b, 35%), while the m-bromo derivative gave high conversions for both chalcogens (7c, Se, 68%; 8c, S, 58%). Polyhalogenated hydrazines highlighted more evident substituent-dependent behavior: the 3,4-dichloro substrate delivered a low yield for selenium (7d, 29%) but remained productive for sulfur (8d, 53%), whereas the 3,5-dichloro analogue gave consistently good results (7f-Se, 68%; 8f-S, 60%). Notably, the 2,5-dichloro and 2,4-dichloro isomers showed a marked decrease in reactivity for selenium (7g-Se, 18%; 8g-S, 51%; 7h-Se, 20%; 8h-S, 48%). Increasing steric congestion appeared to be detrimental to the reaction outcome, as illustrated by the 2,6-dichloro derivatives (7e and 8e), which were unreactive under the optimized conditions for both chalcogens. In contrast, strongly deactivating substituents did not uniformly suppress the reactivity. While para-fluoro (7i and 8i) and ortho-nitro derivatives (7j and 8j) failed to afford the desired products, likely due to electronic and positional effects that may hinder the formation or stabilization of reactive intermediates, the p-CF3 analogue displayed a notable chalcogen-dependent behavior, delivering a moderate 56% yield for selenium (7k) but only 21% for sulfur (8k). This unexpected divergence suggests that subtle electronic and chalcogen-specific effects may influence the efficiency of the transformation. Additionally, attempts to extend the methodology to alkyl-substituted hydrazines as well as to aliphatic nitrile derivatives were unsuccessful under the optimized conditions (7l and 7m).

4. Substrate Scopes for 5-Amino-4-(arylchalcogenyl)-1H-pyrazoles,

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a In a round-bottomed tube, 3-oxo-3-phenylpropanenitrile 1 (0.5 mmol), hydrazine 2 (0.7 mmol), dichalcogenide 5 (0.5 mmol), and solvent (3.0 mL) were added.

b Yields obtained after column chromatography.

In addition, we sought to further explore the synthetic potential of this photochemical protocol by introducing a crossover experiment, which, to the best of our knowledge, has not been investigated in closely related systems. Using meta-bromo hydrazine in combination with two distinct diselenides, para-chloro phenyl diselenide and naphthyl diselenide, the corresponding cross-cyclized products were obtained in 40% (9a) and 30% (9b) yield, respectively. These findings demonstrate that the transformation is not restricted to simple matched substrate pairs but can also accommodate mixed chalcogen sources, thereby expanding the structural diversity accessible through this methodology. Furthermore, compared to previously reported approaches, the current methodology combines operational simplicity with photocatalyst-free conditions and an innovative strategy that incorporates selenium and sulfur derivatives in the same protocol, as corroborated by sustainability metrics (see SI, page S2).

In order to gain further insight into the mechanism of the synthesis of 5-amino-4-(arylselanyl)-1H-pyrazole (4a), several preliminary control experiments were carried out (see Scheme ). Initially, the reaction was performed under optimized conditions but in the absence of iodine, and no product (4a) was observed, indicating the essential role of iodine in the transformation (see Scheme a). This observation is consistent with the optimization studies (Table , entry 20), which showed that halving the iodine amount significantly decreased the yield. Next, radical-trapping experiments were performed using 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) and (2,6-di-tert-butyl-4-methylphenol) BHT, which afforded a 20% yield with TEMPO and only trace amounts with BHT, suggesting that the reaction proceeds predominantly via a radical pathway (Scheme b). To prove the stage at which iodine is crucial, the isolated byproduct (10) was subjected to the optimized conditions in the presence of diphenyl diselenide, affording the selenylated product (4a) in a 95% yield, confirming direct selenylation of this intermediate (Scheme c). Furthermore, the reaction between 1 and 2a under the optimized conditions afforded compound 10 in an 85% yield (Scheme d), as expected, since this compound was identified as a byproduct during the reaction optimization studies. In addition, compound 1 was reacted with 3 under the optimized conditions in an attempt to verify whether a C–H chalcogenated intermediate could be accessed; however, no product formation was observed (Scheme e) Finally, when the reaction was carried out under an inert N2 atmosphere, the yield dramatically decreased to 30% (Scheme f), demonstrating the participation of from air in the course of the reaction.

5. Control Experiments.

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On the basis of the results of our control experiments, as well as the previous literature, a reaction mechanism is proposed (Scheme ). Initially, arylhydrazine (2a) reacts with benzoacetonitrile (1) through a 1,2-addition catalyzed by iodine acting as a Lewis acid, affording the hydrazone intermediate (A). This intermediate then undergoes intramolecular cyclization followed by oxidative aromatization, leading to the formation of 5-amino-1H-pyrazole 10. − Subsequently, the phenylselenyl radical (B) is generated under blue LED irradiation. ,− Addition of radical (B) to compound (10) furnishes the radical intermediate (C), which is subsequently oxidized, likely by molecular oxygen from the air, to afford the cationic intermediate (D). Finally, deprotonation of (D) delivers the desired product (4a).

6. Plausible Mechanism for the Formation of 5-Amino-4-(arylselanyl)-1H-pyrazole (4a).

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In the end, we turned our attention to demonstrating the synthetic application of the obtained chalcogenated pyrazoles and selected 5-amino-4-(phenylselanyl)-1H-pyrazole (4a) as a representative substrate. To further elaborate on this scaffold, we applied the classical Clauson-Kaas reaction, a well-established method for converting aromatic amines into N-substituted heterocycles using 2,5-dimethoxytetrahydrofuran (DMTHF) under acidic conditions. , Accordingly, compound (4a) was stirred in DMTHF with acetic acid at 50 °C for 4 h, affording the pyrrole derivative (11) in an excellent 80% yield (Scheme ). This successful derivatization demonstrates that the selenium-functionalized pyrazole core is fully compatible with downstream synthetic modifications, further underscoring the versatility of the methodology.

7. Synthesis of Pyrrole Derivative 11 .

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Conclusion

In conclusion, we have developed a visible-light-driven, iodine-mediated multicomponent protocol for the efficient synthesis of 5-amino-4-chalcogenyl-1H-pyrazoles under mild reaction conditions. The methodology operates without photocatalysts, transition metals, or external oxidants, using ethyl acetate as a greener solvent and air as an oxidant. Notably, the same optimized conditions are applicable to both diselenides and disulfides without reoptimization, which underscores the robustness and generality of the protocol. A broad substrate scope was demonstrated, providing more than 30 structurally diverse derivatives in good to excellent yields, including gram-scale synthesis and cross-coupling transformations. Mechanistic investigations support a visible-light-induced radical pathway in which photoirradiation plays a crucial role in radical generation. Overall, this operationally simple and environmentally benign strategy provides a versatile platform for accessing chalcogen-functionalized pyrazoles with potential applications in medicinal and material chemistry.

Experimental Section

General Information

The reagents and solvents used in the synthesis were purchased from Sigma-Aldrich Brazil and LabSynth, all of which were used without prior purification. The reactions were monitored by thin-layer chromatography (TLC) using silica gel 60 F254 aluminum sheets, and the visualization of the spots was done under UV light (254 nm), stained with iodine, or by the mixture of 5% vanillin in 10% H2SO4 and heat as developing agents. Column chromatography was performed on silica gel (230–365 mesh). 1H NMR spectra were obtained on a Bruker Avance NEO 500 MHz instrument employing a direct broadband probe at 500 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 used to denote the multiplicity of a particular signal are s (singlet), d (doublet), dd (doublet of doublets), t (triplet), and m (multiplet). 13C­{1H} NMR spectra were obtained on a Bruker Avance NEO 500 MHz employing a direct broadband probe at 125 MHz. The chemical shifts are reported in ppm, referenced to the solvent peak of CDCl3 (δ 77.0 ppm). The melting points of the substances were determined using a Fisatom apparatus (Mod. 430D) series 209219. High-resolution electrospray ionization mass spectrometry (ESI-QTOF) analyses were performed on a Bruker Daltonics micrOTOF-Q II instrument operating in positive mode. Samples were dissolved in HPLC-grade methanol containing 0.1% formic acid and introduced into the ionization source by means of a syringe pump at a flow rate of 5.0 μL/min. Data acquisition and processing were carried out using Compass 1.3 for micrOTOF-Q II software (Bruker Daltonics, Billerica, MA, USA).

General procedure for the synthesis of 5-amino-4-chalcogenyl-1 H -pyrazoles 4, 7–9: By a multicomponent reaction, benzoylacetonitrile 1 (0.5 mmol), hydrazine 2 (1.4 equiv., 0.7 mmol), chalcogenide substrates 3 or 5 (1 equiv., 0.5 mmol), and I2 (50 mol %) in 3 mL of AcOEt were added in a single tube at room temperature for 12 h under magnetic stirring and a blue LED (50W). After that, the remaining iodine was neutralized with saturated Na2S2O3 solution and extracted with ethyl acetate (3 x 10 mL). The organic phase was separated, dried over Na2SO4, filtered, and the solvent evaporated under reduced pressure. The crude material was further purified by column chromatography (hexanes/ethyl acetate) on silica gel.

Note: In the large-scale reaction, 1a (3 mmol, 0.435 g), 2a (4.2 mmol, 0.321 g), 3a (3 mmol, 0.942 g), and I2 (50 mol %, 0.381 g) were used in 18 mL of AcOEt, and product 4a was obtained at 91% yield (1.061 g).

Caution! Hydrazine is toxic and corrosive, and iodine is corrosive and can cause skin and eye irritation. For safety, all manipulations involving these reagents were performed in a well-ventilated fume hood using appropriate personal protective equipment. LED irradiation can irritate the eyes; therefore, appropriate eye protection was used during all of the photochemical experiments.

1,3-Diphenyl-4-(phenylselanyl)-1 H -pyrazol-5-amine (4a): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.186 g (95%); Yellow solid, m.p: 124–125 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.93–7.91 (d, J = 10.0 Hz, 2H); 7.64 (d, J = 5.0 Hz, 2H); 7.45 (t, J = 5.0 Hz 2H); 7.32 (t, J = 5.0 Hz, 3H); 7.28 (d, J = 5.0 Hz, 2H); 7.25 (d, J = 5.0 Hz, 2H); 7.18 (t, J = 5.0, 2H); 7.11 (t, J = 5.0 Hz, 1H); 4.30 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 153.6, 149.5, 138.7, 133.1, 133.0, 129.6, 129.3, 128.2, 128.2, 127.8, 127.6, 125.9, 123.6, 82.4.

4-(Mesitylselanyl)-1,3-diphenyl-1 H -pyrazol-5-amine (4b): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.207 g (67%); Brown oil; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.80 (d, J = 5.0 Hz, 2H); 7.59 (d, J = 10.0 Hz, 2H); 7.45 (t, J = 10.0 Hz 2H); 7.37–7.30 (m, 4H); 4.01 (s, 2H); 2.34 (s, 6H); 2.21 (s, 3H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 153.5, 147.6, 141.6, 138.6, 137.6, 133.6, 129.5, 129.0, 128.2, 128.1, 127.9, 127.9, 127.5, 123.7, 85.0, 24.0, 20.8. HRMS (ESI) m/z: [M + H]+ Calcd for C24H23N3SeH 434.1137; Found: 434.1126.

4-(Naphthalen-1-ylselanyl)-1,3-diphenyl-1 H -pyrazol-5-amine (4e): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.176 g (80%); Brown solid, m.p: 131–132 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 8.12 (d, J = 10.0 Hz, 1H); 7.94 (d, J = 5.0, 2H); 7.85 (d, J = 10.0 Hz, 1H); 7.71 (d, J = 5.0 Hz, 2H); 7.67 (d, J = 10.0 Hz, 1H); 7.56 (m, 4H); 7.50–7.56 (m, 4H); 7.38 (t, J = 5.0 Hz, 1H); 7.32–7.26 (m, 5H); 4.30 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 154.0, 149.6, 138.7, 134.0, 132.9, 132.1, 131.5, 129.6, 128.6, 128.2, 128.2, 127.8, 127.7, 126.3, 126.3, 126.2, 126.1, 125.1, 125.0, 123.7, 81.0. HRMS (ESI) m/z: [M + H]+ Calcd for C25H19N3SeH 442.0818; Found: 442.0814.

1,3-Diphenyl-4-(thiophen-2-ylselanyl)-1 H -pyrazol-5-amine (4f): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.089 g (45%); Brown oil; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 8.00 (d, J = 10.0 Hz, 2H); 7.64 (d, J = 5.0 Hz, 2H); 7.49 (d, J = 5.0 Hz, 2H); 7.42 (d, J = 10.0 Hz, 2H); 7.38–7.35 (m, 2H); 7.26 (d, J = 5.0 Hz, 1H); 7.06 (d, J = 3.5 Hz, 1H); 6.91–6.89 (dd, J = 3.5, 5.0 Hz, 1H); 4.39 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 146.6, 138.1, 136.5, 133.4, 132.4, 131.5, 129.5, 129.1, 129.1, 127.4, 126.4, 125.8, 103.3. MS (APCI) m/z: [M + H]+ Calcd for C19H15N3SSeH 398.02; Found 398.41.

4-(Butylselanyl)-1,3-diphenyl-1 H -pyrazol-5-amine (4g): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.052 g (32%); Brown oil; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 8.08 (d, J = 10.0 Hz, 2H); 7.66 (d, J = 5.0 Hz, 2H); 7.49 (t, J = 10.0 Hz, 2H); 7.41 (t, J = 10.0 Hz, 2H); 7.36–7.32 (m, 2H), 4.30 (s, 2H), 2.56 (t, J = 5.0 Hz, 2H), 1.56–1.50 (m, 2H), 1.36–1.28 (m, 2H), 0.80 (t, J = 5.0 Hz, 3H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 153.0, 149.0, 138.9, 133.6, 129.5, 128.0, 127.9, 127.9, 127.4, 123.5, 83.7, 32.2, 29.2, 22.7, 13.5. HRMS (ESI) m/z: [M + H]+ Calcd for C19H21N3SeH 372.0974; Found: 372.0968.

4-((4-Chlorophenyl)­selanyl)-1,3-diphenyl-1 H -pyrazol-5-amine (4h): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.176 g (83%); Brown oil; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.89 (d, J = 5.0 Hz, 2H); 7.62 (d, J = 5.0 Hz, 2H); 7.45 (t, J = 5.0 Hz, 2H); 7.32–7.21 (m, 4H); 7.00–7.97 (m, 4H), 4.23 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 152.6, 148.4, 137.6, 131.8, 130.9, 130.3, 128.6, 128.3, 128.1, 127.3, 127.2, 126.7, 122.7, 81.1.

4-((4-Fluorophenyl)­selanyl)-1,3-diphenyl-1 H -pyrazol-5-amine (4i): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.133 g (65%); Brown solid, m.p: 123–124 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.92 (d, J = 5.0, 2H); 7.68 (d, J = 10.0 Hz, 2H); 7.51 (t, J = 10.0 Hz, 2H); 7.40–7.31 (m, 4H); 7.25–7.21 (m, 2H); 6.93 (t, J = 10.0, 2H); 4.32 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 162,7, 160.7 (d, J = 250.0 Hz; CC–F), 153.5, 149.4, 138.6, 132.9, 129.8, 129.7, 129.6, 129.5, 128.4, 128.3, 128.2, 127.8, 127.4, 127.3 (d, J C–F = 3.8 Hz; Carom), 125.6, 124.1, 123.7, 116.5, 116.3 (d, J C–F = 21.3 Hz; Carom), 82.8. HRMS (ESI) m/z: [M + H]+ Calcd for C21H16FN3SeH 410.0573; Found: 410.0563.

1,3-Diphenyl-4-((4-(trifluoromethyl)­phenyl)­selanyl)-1 H -pyrazol-5-amine (4j): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.128 g (56%); Orange oil; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.81 (d, J = 5 Hz, 2H); 7.61 (d, J = 5.0 Hz, 2H); 7.45 (t, J = 5.0 Hz, 2H); 7.38 (d, J = 10.0 Hz, 2H); 7.29–7.24 (m, 6H); 4.26 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 152.6, 148.5, 137.62, 137.61 (d, J C–F = 1.3 Hz; Carom), 137.4, 131.6, 128.7 (q, J C–F = 245.0 Hz; CC–F), 128.5 (q, J C–F = 29,3 Hz; Carom), 127.95, 127.90, 127.7, 127.4, 127.2, 127.14 (d, J C–F = 3.6 Hz; Carom), 127.11, 127.0, 126.9, 126.7, 124.9 (q, J C–F = 3.5 Hz; Carom), 124.6, 124.2, 123.1, 122.7, 122.3, 120.7, 80.15. HRMS (ESI) m/z: [M + H]+ Calcd for C22H16F3N3SeH 460.0535; Found: 460.0531.

1,3-Diphenyl-4-(phenylthio)-1 H -pyrazol-5-amine (6a): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.168 g (98%); Brow oil; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.95 (d, J = 5.0 Hz, 2H); 7.68 (d, J = 10.0 Hz, 2H); 7.51 (t, J = 10.0 Hz, 2H); 7.38 (d, J = 10.0 Hz, 1H); 7.36–7.29 (m, 3H); 7.24 (t, J = 10.0 Hz, 2H); 7.16 (d, J = 5.0, 2H); 7.10 (t, J = 5.0 Hz, 1H); 4.30 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 153.4, 149.5, 138.6, 138.1, 132.5, 129.6, 129.0, 128.3, 128.3, 128.2, 127.7, 127.5, 125.1, 125.1, 123.6, 86.3.

1,3-Diphenyl-4-(p-tolylthio)-1 H -pyrazol-5-amine (6b): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.148 g (83%); Beige solid, m.p: 126–127 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.89 (d, J = 10.0 Hz, 2H); 7.62 (d, J = 10.0 Hz, 2H); 7.44 (t, J = 5.0 Hz, 2H); 7.32 (d, J = 5.0 Hz, 1H); 7.29 (m, 3H); 7.01 (t, J = 5.0 Hz, 4H); 4.24 (s, 2H); 2.21 (s, 3H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 153.3, 149.4, 138.6, 134.9, 134.5, 132.6, 129.8, 129.65, 128.2, 128.2, 127.7, 127.5, 125.3, 123.6, 86.8, 20.9.

1,3-Diphenyl-4-(m-tolylthio)-1 H -pyrazol-5-amine (6c): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.135 g (76%); Yellow solid, m.p: 127–128 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.95 (d, J = 10.0, Hz, 2H); 7.68 (d, J = 10.0 Hz, 2H); 7.50 (t, J = 5.0 Hz, 2H); 7.37 (d, J = 10.0 Hz, 1H); 7.35–7.27 (m, 3H); 7.12 (t, J = 5.0 Hz, 1H); 6.98 (s, 1H); 6.93 (dd, J = 10.0, 5.0 Hz, 2H); 4.29 (s, 2H); 2.27 (s, 3H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 153.4, 149.5, 138.8, 138.6, 137.9, 132.6, 129.6, 128.9, 128.2, 127.7, 127.5, 126.0, 125.7, 123.5, 122.2, 86.4, 21.4. HRMS (ESI) m/z: [M + H]+ Calcd for C22H19N3SH 358.1372; Found: 358.1374.

1,3-Diphenyl-4-(o-tolylthio)-1 H -pyrazol-5-amine (6d): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.125 g (50%); Brown solid, m.p: 89–90 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.83 (d, J = 10.0 Hz, 2H); 7.61 (d, J = 10.0 Hz, 2H); 7.43 (t, J = 5.0 Hz, 2H); 7.30 (t, J = 5.0 Hz, 1H); 7.26–7.21 (m, 3H); 7.07 (d, J = 5.0 Hz, 1H); 6.85 (d, J = 5.0, Hz, 1H); 4.19 (s, 2H); 2.36 (s, 3H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 153.6, 149.4, 138.6, 136.8, 134.4, 132.5, 130.1, 129.6, 128.2, 128.2, 127.7, 127.5, 126.6, 124.7, 124.7, 123.9, 123.6, 85.5, 19.7. HRMS (ESI) m/z: [M + H]+ Calcd for C22H19N3SH 358.137245; Found: 358.1368.

4-((4-Fluorophenyl)­thio)-1,3-diphenyl-1H-pyrazol-5-amine (6e): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.090 g (50%); Yellow solid, m.p: 103–104 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.93 (d, J = 10.0 Hz, 2H); 7.68 (d, J = 7.6 Hz, 2H); 7.52 (t, J = 7.9 Hz, 2H); 7.39 (t, J = 7.5 Hz, 1H); 7.36–7.31 (m, 3H); 7.20 (d, J = 8.6 Hz, 2H), 7.08 (d, J = 8.6 Hz, 2H), 4.32 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 162,1, 160.2 (d, J = 245.0 Hz; Carom), 153.3, 149.6, 138.6, 133.2 (d, J C–F = 3.0 Hz; Carom), 132.6, 129.8, 128.5, 128.4, 127.9, 127.6, 127.1, 127.0 (d, J C–F = 8.0 Hz; Carom), 123.7, 116.3, 116.1 (d, J C–F = 22.0 Hz; Carom), 86.8. HRMS (ESI) m/z: [M + H]+ Calcd for C21H16FN3SH 362.1121; Found: 362.1117.

4-((4-Chlorophenyl)­thio)-1,3-diphenyl-1 H -pyrazol-5-amine (6f): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.113 g (60%); Yellow solid, m.p: 111–113 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.94–7.91 (m, 2H); 7.68 (d, J = 7.6 Hz, 2H); 7.52 (t, J = 7.9 Hz, 2H); 7.39 (t, J = 7.5 Hz, 1H); 7.36–7.31 (m, 3H); 7.20 (d, J = 8.6 Hz, 2H), 7.08 (d, J = 8.6 Hz, 2H), 4.32 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 153.3, 149.5, 138.5, 136.8, 132.4, 131.0, 129.7, 129.1, 128.4, 128.3, 127.8, 127.4, 126.4, 123.6, 85.8.

3-Phenyl-4-(phenylselanyl)-1-(o-tolyl)-1 H -pyrazol-5-amine (7a): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.060 g (30%); Yellow oil; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.86–7.83 (m, 2H); 7.34 (d, J = 7.5 Hz, 1H); 7.30–7.27 (m, 2H); 7.25 (t, J = 7.1 Hz, 3H); 7.21 (d, J = 7.1 Hz, 1H); 7.19 (d, J = 7.2 Hz, 2H); 7.13 (t, J = 7.5 Hz, 2H); 7.06 (t, J = 7.2 Hz, 1H); 3.95 (s, 2H); 2.16 (s, 3H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 153.3, 150.2, 136.7, 136.8, 133.4, 133.1, 131.5, 129.8, 128.1, 128.0, 127.8, 127.6, 127.0, 125.7, 80.3, 17.5.

1-(4-Bromophenyl)-3-phenyl-4-(phenylselanyl)-1 H -pyrazol-5-amine (7b): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.197 g (84%); Yellowish solid, m.p: 133–134 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.91 (d, J = 9.7 Hz, 2H); 7.65–7.60 (m, 4H); 7.37–7.32 (m, 3H); 7.27 (d, J = 9.8 Hz, 2H); 7.24–7.20 (m, 2H); 7.18–7.14 (m, 1H); 4.31 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 154.0, 149.5, 137.8, 132.8, 132.8, 132.7, 129.3, 128.4, 128.2, 127.9, 127.8, 126.0, 125.0, 121.1, 83.2 HRMS (ESI) m/z: [M + H]+ Calcd for C21H16BrN3SeH 469.9773; Found: 469.9756.

1-(3-Bromophenyl)-3-phenyl-4-(phenylselanyl)-1 H -pyrazol-5-amine (7c): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.159 g (68%); Yellowish oil; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.86 (m, 3H); 7.60 (d, J = 9.8 Hz, 1H); 7.44 (d, J = 8.8 Hz, 1H); 7.31 (d, J = 8.1 Hz, 1H); 7.29–7.25 (m, 3H); 7.21–7.16 (m, 3H); 7.15 (t, J = 7.5 Hz, 2H); 7.11–7.08 (m, 1H); 4.28 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 154.1, 149.6, 139.9, 132.8, 132.7, 130.8, 130.6, 129.4, 128.4, 128.2, 127.9, 127.9, 126.6, 126.0, 123.2, 121.7, 83.2. HRMS (ESI) m/z: [M + H]+ Calcd for C21H16BrN3SeH 469.9763; Found: 469.9756.

1-(3,4-Dichlorophenyl)-3-phenyl-4-(phenylselanyl)-1 H -pyrazol-5-amine (7d): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.066 g (29%); Yellowish oil; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.84 (d, J = 7.8 Hz, 3H); 7.55 (dd, J = 8.6, 2.3 Hz, 1H); 7.51 (d, J = 8.6 Hz, 1H); 7.31–7.26 (m, 3H); 7.19–7.14 (m, 4H); 7.10 (t, J = 7.0 Hz, 1H); 4.27 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 154.2, 149.5, 138.0, 133.5, 132.6, 132.5, 131.3, 131.0, 129.3, 128.5, 128.2, 127.9, 127.8, 126.0, 125.0, 122.0, 83.8, 77.0. HRMS (ESI) m/z: [M + H]+ Calcd for C21H15Cl2N3SeH 459.9877; Found: 459.9874.

1-(3,5-Dichlorophenyl)-3-phenyl-4-(phenylselanyl)-1 H -pyrazol-5-amine (7f): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.156 g (68%); Yellowish solid, m.p: 122–123 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.82 (dd, J = 8.0, 1.6 Hz, 2H); 7.62 (d, J = 1.8 Hz, 2H); 7.30–7.25 (m, 4H); 7.18–7.12 (m, 4H); 7.10–7.07 (m, 1H); 4.29 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 154.5, 149.6, 140.5, 135.9, 129.4, 128.6, 128.2, 128.0, 127.8, 127.2, 126.1, 114.3, 84.1. HRMS (ESI) m/z: [M + H]+ Calcd for C21H15Cl2N3SeH 459.9877; Found: 459.9875.

1-(2,5-Dichlorophenyl)-3-phenyl-4-(phenylselanyl)-1 H -pyrazol-5-amine (7g): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.041 g (18%); Orange solid, m.p: 158–159 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.81 (dd, J = 8.1, 1.5 Hz, 2H); 7.56 (d, J = 2.5 Hz, 1H); 7.41 (d, J = 8.7 Hz, 1H); 7.33 (dd, J = 8.7, 2.5 Hz, 1H); 7.28–7.23 (m, 3H); 7.19–7.13 (m, 5H); 7.08 (t, J = 7.1 Hz, 1H); 4.10 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 154.6, 150.9, 136.7, 133.6, 132.9, 132.6, 131.3, 130.8, 130.2, 130.1, 129.3, 128.4, 128.1, 127.9, 127.7, 125.9, 81.9. HRMS (ESI) m/z: [M + H]+ Calcd for C21H15Cl2N3SeH 459.9877; Found: 459.9877.

1-(2,4-Dichlorophenyl)-3-phenyl-4-(phenylselanyl)-1 H -pyrazol-5-amine (7h): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.046 g (20%); Brown solid, m.p: 149–150 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.81 (dd, J = 8.1, 1.5 Hz, 2H); 7.52 (d, J = 2.2 Hz, 1H); 7.48 (d, J = 8.5 hz, 1H); 7.35 (dd, J = 8.5, 2.3 Hz, 1H); 7.29–7.24 (m, 3H); 7.19–7.13 (m, 4H); 7.08 (t, J = 7.1 Hz, 1H); 4.07 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 154.5, 151.0, 136.2, 134.5, 133.0, 132.9, 132.7, 130.9, 130.4, 129.3, 128.5, 128.4, 128.2, 127.9, 127.7, 125.9, 81.8.

3-Phenyl-4-(phenylselanyl)-1-(4-(trifluoromethyl)­phenyl)-1 H -pyrazol-5-amine (7k): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.128 g (56%); Brown solid, m.p: 72–73 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.85 (dd, J = 8.0, 1.4 Hz, 2H); 7.82 (d, J = 8.4 Hz, 2H); 7.70 (d, J = 8.5 Hz, 2H); 7.31–7.26 (m, 3H); 7.19 (t, J = 5.9 Hz, 2H); 7.15 (t, J = 7.4 Hz, 2H); 7.09 (t, J = 7.1 Hz, 1H); 4.31 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 170.0, 137.8, 131.5, 130.5, 129.9, 129.0, 128.8, 128.2, 127.8, 126.7, 123.1, 100.7. HRMS (ESI) m/z: [M + H]+ Calcd for C22H16F3N3SeH 460.0535; Found: 460.0543.

3-Phenyl-4-(phenylthio)-1-(o-tolyl)-1 H -pyrazol-5-amine (8a): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.080 g (45%), Orange oil; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.94 (d, J = 8.2 Hz, 2H); 7.42 (d, J = 7.5 Hz, 1H); 7.39–7.36 (m, 2H); 7.35–7.28 (m, 2H); 7.24 (t, J = 7.7 Hz, 2H); 7.16 (d, J = 8.3 Hz, 2H); 7.10 (t, J = 7.2 Hz, 1H); 4.03 (s, 2H); 2.25 (s, 3H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 153.0, 150.2, 138.5, 136.6, 136.5, 132.7, 131.5, 129.8, 129.0, 128.2, 128.1, 127.8, 127.5, 127.1, 125.0, 84.3, 17.6. HRMS (ESI) m/z: [M + H]+ Calcd for C22H19N3SH 358.1372; Found: 358.1375.

1-(4-Bromophenyl)-3-phenyl-4-(phenylthio)-1 H -pyrazol-5-amine (8b): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.073 g (35%); Brown solid, m.p: 128–129 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.85 (d, J = 9.7 Hz, 2H); 7.54 (d, J = 8.9 Hz, 2H); 7.50 (d, J = 8.9 Hz, 2H); 7.27–7.22 (m, 3H); 7.18–7.13 (m, 2H); 7.07 (dd, J = 8.4, 1.1 Hz, 2H); 7.03 (t, J = 7.3 Hz, 1H); 4.21 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 153.7, 149.5, 137.8, 137.6, 132.7, 132.3, 129.1, 128.4, 128.3, 127.5, 125.2, 125.2, 124.8, 121.1, 87.0.

1-(3-Bromophenyl)-3-phenyl-4-(phenylthio)-1 H -pyrazol-5-amine (8c): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.122 g (58%), Orange oil; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.86–7.83 (m, 3H); 7.57 (d, J = 10.9 Hz, 1H); 7.43 (d, J = 10.8 Hz, 1H); 7.29–7.23 (m, 4H); 7.19–7.14 (m, 2H); 7.07 (dd, J = 8.4, 1.1 Hz, 2H); 7.04 (t, J = 7.3 Hz, 1H); 4.26 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 153.8, 149.6, 139.8, 137.8, 132.2, 130.8, 130.6, 129.1, 128.5, 128.3, 127.5, 126.5, 125.2, 125.2, 123.2, 121.6, 87.1.

1-(3,4-Dichlorophenyl)-3-phenyl-4-(phenylthio)-1 H -pyrazol-5-amine (8d): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.109 g (53%); Orange oil; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.83 (dd, J = 8.0, 1.6 Hz, 2H); 7.78 (s, 1H); 7.49–7.43 (m, 2H); 7.27–7.22 (m, 3H); 7.17–7.12 (m, 2H); 7.06–7.01 (m, 4H); 4.25 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 171.13, 154.13, 149.90, 138.32, 137.88, 133.84, 132.46, 131.56, 131.29, 129.28, 128.73, 128.45, 127.75, 125.66, 125.55, 125.16, 122.21, 88.30. HRMS (ESI) m/z: [M + H]+ Calcd for C21H15Cl2N3SH 412.0436; Found: 412.0434.

1-(3,5-Dichlorophenyl)-3-phenyl-4-(phenylthio)-1H-pyrazol-5-amine (8f): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.057 g (60%); Orange oil; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.92 (dd, J = 8.0, 1.6 Hz, 2H); 7.67 (s, 2H); 7.35–7.30 (m, 4H); 7.23–7.21 (m, 2H); 7.13–7.08 (m, 3H); 4.35 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 154.12, 149.69, 140.35, 137.50, 135.91, 131.99, 129.10, 128.64, 128.30, 127.50, 127.24, 125.33, 125.25, 87.99. HRMS (ESI) m/z: [M + H]+ Calcd for C21H15Cl2N3S [M + H]+: 412.0436; Found: 412.0433.

1-(2,5-Dichlorophenyl)-3-phenyl-4-(phenylthio)-1 H -pyrazol-5-amine (8g): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.105 g (51%); Orange solid, m.p: 142–142 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.83 (d, J = 9.7 Hz, 2H); 7.56 (d, J = 2.4 Hz, 1H); 7.42 (d, J = 8.7 Hz, 1H); 7.34 (dd, J = 8.7, 2.5, Hz, 1H); 7.27–7.23 (m, 3H); 7.17 (t, J = 7.7 Hz, 2H); 7.08 (d, J = 9.6 Hz, 2H); 7.05–7.01 (m, 1H); 4.10 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 154.3, 150.8, 137.8, 136.6, 133.7, 132.2, 131.3, 130.9, 130.2, 129.1, 128.5, 128.2, 127.5, 125.1, 125.0, 85.9. HRMS (ESI) m/z: [M + H]+ Calcd for C21H15Cl2N3SH 412.0436; Found: 412.0437.

1-(2,4-Dichlorophenyl)-3-phenyl-4-(phenylthio)-1 H -pyrazol-5-amine (8h): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.098 g (48%); Beige solid, m.p: 150–151 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.83 (dd, J = 8.0, 1.5 Hz, 2H); 7.52 (d, J = 2.2 Hz, 1H); 7.46 (d, J = 8.5 Hz, 1H); 7.34 (dd, J = 8.5, 2.2 Hz, 1H); 7.27–7.22 (m, 3H); 7.17 (t, J = 7.7 Hz, 2H); 7.08 (d, J = 7.4 Hz, 2H); 7.03 (t, J = 7.3 Hz, 1H); 4.06 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 154.2, 150.9, 138.0, 136.3, 134.3, 132.8, 132.2, 130.8, 130.4, 129.1, 128.8, 128.4, 128.2, 127.5, 125.1, 125.0, 85.7. HRMS (ESI) m/z: [M + H]+ Calcd for C21H15Cl2N3SH 412.0436; Found: 412.0434.

1-(4-Fluorophenyl)-3-phenyl-4-(phenylthio)-1 H -pyrazol-5-amine (8k): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.090 g (21%); Brown oil;1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.94 (d, J = 9.7 Hz, 2H); 7.66 (d, J = 9.6 Hz, 2H); 7.49 (t, J = 7.9 Hz, 2H); 7.38 (d, J = 8.5 Hz, 1H); 7.35–7.30 (m, 4H); 7.12–7.09 (m, 2H); 6.93 (t, J = 8.7 Hz, 2H); 4.32 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 154.17, 149.75, 141.65, 137.66, 132.19, 129.43, 129.16 (q, J = 235.0 Hz; CC–F), 129.07, 128.65, 128.37, 127.55 (d, J C–F = 5.3 Hz; Carom), 126.88 (q, J J C–F = 3.6 Hz; Carom), 125.32 (d, J C–F = 7.8 Hz; Carom), 123.00, 114.17, 87.87.

1-(4-Bromophenyl)-4-((4-chlorophenyl)­selanyl)-3-phenyl-1 H -pyrazol-5-amine (9a): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.075 g (40%); Orange oil; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.87 (m, 2H), 7.61 (d, J = 8.8 Hz, 2H), 7.56 (d, J = 8.8 Hz, 2H), 7.36–7.30 (m, 2H), 7.16 (s, 4H), 4.30 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 153.85, 149.45, 137.60, 132.69, 132.56, 132.04, 131.10, 129.39, 129.22, 128.46, 128.23, 127.73, 124.89, 121.20, 82.83. HRMS (ESI) m/z: [M + H]+ Calcd for C21H15BrClN3SeH 503.9371; Found: 503.9376.

1-(4-Bromophenyl)-4-(naphthalen-1-ylselanyl)-3-phenyl-1 H -pyrazol-5-amine (9b): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.060 g (30%); Orange oil; 1H NMR (CDCl3, 500 MHz) δ (ppm) = (d, J = 8.0 Hz, 1H), 7.93 – 7.88 (m, 2H), 7.84 (d, J = 7.6 Hz, 1H), 7.68 – 7.65 (m, 1H), 7.60 (d, J = 2.5 Hz, 3H), 7.56 – 7.48 (m, 2H), 7.30 (d, J = 6.8 Hz, 3H), 7.27 – 7.24 (m, 2H), 4.27 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 154.36, 149.58, 137.76, 134.03, 132.69, 132.08, 131.30, 128.64, 128.41, 128.23, 127.78, 126.43, 126.29, 126.25, 125.09, 124.92, 121.12, 81.79. HRMS (ESI) m/z: [M + H]+ Calcd for C25H18BrN3SeH 519.9920; Found: 519.9920.

General procedure for the synthesis of 1,3-diphenyl-1H-pyrazol-5-amine (10): In a sealed tube, benzoacetonitrile (1, 1.0 mmol, 0.145 g) and phenylhydrazine (2a, 1.0 mmol, 0.107 g) were dissolved in glacial acetic acid (10 mL). The reaction mixture was stirred at 50 °C for 1 h, and the progress was monitored by TLC. After completion, the reaction was cooled to room temperature and poured into water (20 mL). The mixture was extracted with ethyl acetate (3 × 15 mL). The combined organic layers were washed with water, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford the desired product as a crude solid/oil, which was used in the next step without further purification.

1,3-Diphenyl-1H-pyrazol-5-amine (10): Purified by column chromatography (hexane/ethyl acetate = 95:5); Yield: 0.230 g (90%); Orange oil; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.82 −7.78 (m, 2H), 7.63 −7.59 (m, 2H), 7.47 (t, J = 7.9 Hz, 2H), 7.39 – 7.26 (m, 6H), 5.93 (s, 1H), 3.84 (s, 2H). 13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 187.11, 151.46, 145.85, 138.65, 129.48, 129.11, 128.48, 127.80, 127.41, 125.60, 124.10, 113.78, 88.12.

General procedure for the synthesis of 1,3-Diphenyl-4-(phenylselanyl)-5-(1H-pyrrol-1-yl)-1 H -pyrazole (11): In a sealed tube, compound 4a (1.0 mmol, 0.389 g) and 2,5-dimethoxytetrahydrofuran (DMTHF, 1 equiv., 1.0 mmol, 0.132 g) were dissolved in acetic acid (3.0 mL). The reaction mixture was stirred at 120 °C until completion (monitored by TLC). After cooling to room temperature, the mixture was diluted with water and carefully neutralized with a saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted with ethyl acetate (3 × 10 mL). The combined organic layers were washed with water, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel using hexane/ethyl acetate (9:1, v/v) as the eluent to afford the desired product.

Caution: Reactions conducted at elevated temperatures were performed using robust glassware, positioned behind an appropriate safety shield.

1,3-Diphenyl-4-(phenylselanyl)-5-(1H-pyrrol-1-yl)-1 H -pyrazole (11): Purified by column chromatography (hexane/ethyl acetate = 97:3); Yield: 0.106 g (80%); Yellowish solid, m.p: 201–202 °C; 1H NMR (CDCl3, 500 MHz) δ (ppm) = 7.89 (d, J = 8.4 Hz, 2H), 7.43 (t, J = 7.5 Hz, 3H), 7.35 (d, J = 21.6 Hz, 4H), 7.29 (d, J = 7.2 Hz, 1H), 7.22 (d, J = 8.6 Hz, 1H), 6.70 (dd, J = 4.8, 2.7 Hz, 3H), 6.28 (t, J = 2.1 Hz, 2H).13C­{1H} NMR (CDCl3, 126 MHz) δ (ppm) = 151.36, 138.37, 132.65, 129.09, 128.70, 128.35, 127.54, 125.64, 122.97, 122.13, 110.61, 100.02. HRMS (ESI) m/z: [M + H]+ Calcd for C25H19N3SeH 442.0818; Found: 442.0824.

Supplementary Material

jo6c00605_si_001.pdf (3MB, pdf)

Acknowledgments

This study was financed in part by Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq (VN. 306952/2025-4 and 401315/2025-8) and Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior (CAPES). VN thanks the Fundação Carlos Chagas Filho de Amparo à Pesquisa no Estado do Rio de Janeiro (E-26/210.325/2022 and E-26/204.376/2025) and L’ORÉAL-UNESCO-ABC Para Mulheres na Ciência for financial support.

The data underlying this study are available in the published article and its Supporting Information. Copies of (1H and 13C) NMR spectra of the compounds.

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.joc.6c00605.

  • Reaction setup and photochemical reaction under blue LED (Figure S1); 1H NMR and 13C­{1H} spectra of compounds 4a–j (Figure S2–17); 1H and 13C­{1H} NMR spectra of compounds 6a–f (Figure S18–29); 1H and 13C­{1H} NMR spectra of compounds 7a–c (Figure S30–35); 1H and 13C­{1H} NMR spectra of compound 7d (Figure S36, 37); 1H and 13C­{1H} NMR spectra of compound 7f (Figure S38, 39); 1H and 13C­{1H} NMR spectra of compound 7g (Figure S40, 41); 1H and 13C­{1H} NMR spectra of compound 7h (Figure S42, 43); 1H and 13C­{1H} NMR spectra of compound 7k (Figure S44, 45); 1H and 13C­{1H} NMR spectra of compound 8a (Figure S46, 47); 1H and 13C­{1H} NMR spectra of compound 8b (Figure S48, 49); 1H and 13C­{1H} NMR spectra of compound 8c (Figure S50, 51); 1H and 13C­{1H} NMR spectra of compound 8d (Figure S52, 53); 1H and 13C­{1H} NMR spectra of compound 8f (Figure S54, 55); 1H and 13C­{1H} NMR spectra of compound 8g (Figure S56, 57); 1H and 13C­{1H} NMR spectra of compound 8h (Figure S58, 59); 1H and 13C­{1H} NMR spectra of compound 8k (Figure S60, 61); 1H and 13C­{1H} NMR spectra of compound 9a (Figure S62, 63); 1H and 13C­{1H} NMR spectra of compound 9b (Figure S64, 65); 1H and 13C­{1H} NMR spectra of compound 10 (Figure S66, 67); and 1H and 13C­{1H} NMR spectra of compound 11 (Figure S68, 69) (PD)

The Article Processing Charge for the publication of this research was funded by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazil (ROR identifier: 00x0ma614).

The authors declare no competing financial interest.

References

  1. Moussa Z., Ramanathan M., Alharmoozi S. M., Alkaabi S. A. S., Al Aryani S. H. M., Ahmed S. A., Al-Masri H. T.. Recent Highlights in the Synthesis and Biological Significance of Pyrazole Derivatives. Heliyon. 2024;10(20):e38894. doi: 10.1016/j.heliyon.2024.e38894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Kumar V., Kaur K., Gupta G. K., Sharma A. K.. Pyrazole Containing Natural Products: Synthetic Preview and Biological Significance. Eur. J. Med. Chem. 2013;69:735–753. doi: 10.1016/j.ejmech.2013.08.053. [DOI] [PubMed] [Google Scholar]
  3. Naim M., Alam O., Nawaz F., Alam M., Alam J. P.. Current Status of Pyrazole and Its Biological Activities. J. Pharm. Bioall. Sci. 2016;8(1):2. doi: 10.4103/0975-7406.171694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gimła M., Pyrczak-Felczykowska A., Malinowska M., Hać A., Narajczyk M., Bylińska I., Reekie T. A., Herman-Antosiewicz A.. The Pyrazole Derivative of Usnic Acid Inhibits the Proliferation of Pancreatic Cancer Cells in Vitro and in Vivo. Cancer Cell Int. 2023;23(1):210. doi: 10.1186/s12935-023-03054-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Shaker A. M. M., Shahin M. I., AboulMagd A. M., Abdel-Rahman H. M., Ella D. A. A. E.. Design, Synthesis, and Molecular Docking of Novel 1,3, 4-Triaryl Pyrazole Derivatives Bearing Methylsulfonyl Moiety with Anticancer Activity through Dual Targeting CDK2 and COX-2 Enzymes. J. Mol. Struct. 2024;1301:137323. doi: 10.1016/j.molstruc.2023.137323. [DOI] [Google Scholar]
  6. Mantzanidou M., Pontiki E., Hadjipavlou-Litina D.. Pyrazoles and Pyrazolines as Anti-Inflammatory Agents. Molecules. 2021;26(11):3439. doi: 10.3390/molecules26113439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kumar R., Sharma R., Sharma D. K.. Pyrazole; A Privileged Scaffold of Medicinal Chemistry: A ComprehensiveReview. Curr. Top. Med. Chem. 2023;23(22):2097–2115. doi: 10.2174/1568026623666230714161726. [DOI] [PubMed] [Google Scholar]
  8. Abd El-Karim S. S., Anwar M. M., Syam Y. M., Awad H. M., El-Dein A. N., El-Ashrey M. K., Alkahtani H. M., Abdelwahed S. H.. New Benzofuran–Pyrazole-Based Compounds as Promising Antimicrobial Agents: Design, Synthesis, DNA Gyrase B Inhibition, and In Silico Studies. Pharmaceuticals. 2024;17(12):1664. doi: 10.3390/ph17121664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Matta R., Pochampally J., Dhoddi B. N., Bhookya S., Bitla S., Akkiraju A. G.. Synthesis, Antimicrobial and Antioxidant Activity of Triazole, Pyrazole Containing Thiazole Derivatives and Molecular Docking Studies on COVID-19. BMC Chem. 2023;17(1):61. doi: 10.1186/s13065-023-00965-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Zhou J., Zhou Q., Wan J.-P.. Recent Advances in the Multicomponent Synthesis of Pyrazoles. Org. Biomol. Chem. 2024;22(40):8065–8077. doi: 10.1039/D4OB01211A. [DOI] [PubMed] [Google Scholar]
  11. Ebenezer O., Shapi M., Tuszynski J. A.. A Review of the Recent Development in the Synthesis and Biological Evaluations of Pyrazole Derivatives. Biomedicines. 2022;10(5):1124. doi: 10.3390/biomedicines10051124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Devi L., Sharma G., Kant R., Shukla S. K., Rastogi N.. Regioselective Synthesis of Functionalized Pyrazole-Chalcones via a Base Mediated Reaction of Diazo Compounds with Pyrylium Salts. Org. Biomol. Chem. 2021;19(18):4132–4136. doi: 10.1039/D1OB00274K. [DOI] [PubMed] [Google Scholar]
  13. Gulia N., Daugulis O.. Palladium-Catalyzed Pyrazole-Directed Sp3 C–H Bond Arylation for the Synthesis of β-Phenethylamines. Angew. Chem., Int. Ed. 2017;56(13):3630–3634. doi: 10.1002/anie.201611407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nobre P. C., Cordeiro P., Chipoline I. C., Menezes V., Santos K. V. S., Ángel A. Y. B., Alberto E. E., Nascimento V.. Telluride-Based Pillar­[5]­Arene: A Recyclable Catalyst for Alkylation Reactions in Aqueous Solution. J. Org. Chem. 2024;89(18):12982–12988. doi: 10.1021/acs.joc.4c00997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ángel A. Y. B., Campos P. R. O., Alberto E. E.. Selenonium Salt as a Catalyst for Nucleophilic Substitution Reactions in Water: Synthesis of Thiocyanites and Selenocyanates. Molecules. 2023;28(7):3056. doi: 10.3390/molecules28073056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Cordeiro P., Menezes V., Ángel A. Y. B., De Andrade K. N., Fiorot R. G., Alberto E. E., Nascimento V.. Chalcogen Bond-Driven Alkylations: Selenoxide-Pillar[5]­Arene as a Recyclable Catalyst for Displacement Reactions in Water. Chem. - Asian J. 2025;20(2):e202400916. doi: 10.1002/asia.202400916. [DOI] [PubMed] [Google Scholar]
  17. Azevedo A. R., Nobre P. C., Köhler M. H., Iglesias B. A., Nascimento V.. Design, Synthesis, Photophysical, Theoretical, and Electrochemical Characterization of Novel Organochalcogen-DHPM-Triazole Hybrids. ChemistrySelect. 2025;10(22):e02730. doi: 10.1002/slct.202502730. [DOI] [Google Scholar]
  18. Gomes L. S., Silva M. C., Nobre P. C., Peglow T. J., Nascimento V.. Synthesis of 2,3-Dihydrobenzofuran Chalcogenides Under Visible Light: A Sustainable Approach. Processes. 2025;13(4):1038. doi: 10.3390/pr13041038. [DOI] [Google Scholar]
  19. Fernandes C. M., Cordeiro P., Menezes V., Martins V., Dos Reis J. S., Lee H.-S., Nascimento V., Lgaz H., Ponzio E. A.. Selenocyanates and Selenotetrazoles Derivatives: A Detailed Experimental and Theoretical Evaluation as Corrosion Inhibitors for Mild Steel in Aggressive Environment. Electrochim. Acta. 2024;475:143629. doi: 10.1016/j.electacta.2023.143629. [DOI] [Google Scholar]
  20. Campos P. R. O., Silva G. P. P. P., Shibuya Y., Koguchi S., Alberto E. E.. Oxidation Reactions Promoted or Catalyzed by Organotellurium Compounds. ACS Omega. 2025;10(27):28691–28708. doi: 10.1021/acsomega.5c03157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Piętka-Ottlik M., Wójtowicz-Młochowska H., Kołodziejczyk K., Piasecki E., Młochowski J.. New Organoselenium Compounds Active against Pathogenic Bacteria, Fungi and Viruses. Chem. Pharm. Bull. 2008;56(10):1423–1427. doi: 10.1248/cpb.56.1423. [DOI] [PubMed] [Google Scholar]
  22. Fonseca S. F., Lima D. B., Alves D., Jacob R. G., Perin G., Lenardão E. J., Savegnago L.. Synthesis, Characterization and Antioxidant Activity of Organoselenium and Organotellurium Compound Derivatives of Chrysin. New J. Chem. 2015;39(4):3043–3050. doi: 10.1039/C4NJ02329C. [DOI] [Google Scholar]
  23. Gandhi V. V., Priyadarsini K. I., Kunwar A.. Paradoxical Behavior of Organodiselenides: Pro-Oxidant to Antioxidant. Chem. Proc. 2020;2:6. doi: 10.3390/ECCS2020-07552. [DOI] [Google Scholar]
  24. Lu X., Mestres G., Singh V., Effati P., Poon J.-F., Engman L., Ott M.. Selenium- and Tellurium-Based Antioxidants for Modulating Inflammation and Effects on Osteoblastic Activity. Antioxidants. 2017;6(1):13. doi: 10.3390/antiox6010013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Savegnago L., Pinto L. G., Jesse C. R., Alves D., Rocha J. B. T., Nogueira C. W., Zeni G.. Antinociceptive Properties of Diphenyl Diselenide: Evidences for the Mechanism of Action. Eur. J. Pharmacol. 2007;555(2–3):129–138. doi: 10.1016/j.ejphar.2006.10.003. [DOI] [PubMed] [Google Scholar]
  26. Jacob R. G., Hartwig D., Nascimento J. E. R., Abib P. B., Ebersol C. P., Nunes P. P. P., Birmann P. T., Casaril A. M., Savegnago L., Schumacher R. F.. Sequential One-Pot Synthesis and Antioxidant Evaluation of 5-Amino-4-(Arylselanyl)-1H-Pyrazoles. Tetrahedron Lett. 2022;103:153992. doi: 10.1016/j.tetlet.2022.153992. [DOI] [Google Scholar]
  27. Ali D., Parvin T., Choudhury L. H.. Visible Light-Mediated C­(Sp2)–H Selenylation of Amino Pyrazole and Amino Uracils in the Presence of Rose Bengal as an Organophotocatalyst. J. Org. Chem. 2022;87(2):1230–1239. doi: 10.1021/acs.joc.1c02565. [DOI] [PubMed] [Google Scholar]
  28. Pires C. S., De Oliveira D. H., Pontel M. R. B., Kazmierczak J. C., Cargnelutti R., Alves D., Jacob R. G., Schumacher R. F.. Molecular Iodine-Catalyzed One-Pot Multicomponent Synthesis of 5-Amino-4-(Arylselanyl)-1 H -Pyrazoles. Beilstein J. Org. Chem. 2018;14:2789–2798. doi: 10.3762/bjoc.14.256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Annes S. B., Saritha R., Chandru K., Mandali P. K., Ramesh S.. Metal- and Solvent-Free Cascade Reaction for the Synthesis of Amino Pyrazole Thioether Derivatives. J. Org. Chem. 2021;86(23):16473–16484. doi: 10.1021/acs.joc.1c01846. [DOI] [PubMed] [Google Scholar]
  30. Huang Z., Wu H., Geng M., Kuang J., Ma Y.. Sodium Iodide-Promoted Construction of Fully Substituted 4-Sulfenyl-5-Aminopyrazole Derivatives. J. Org. Chem. 2025;90(22):7396–7405. doi: 10.1021/acs.joc.5c00667. [DOI] [PubMed] [Google Scholar]
  31. Sun J., Qiu J.-K., Zhu Y.-L., Guo C., Hao W.-J., Jiang B., Tu S.-J.. Metal-Free Iodine-Catalyzed Synthesis of Fully Substituted Pyrazoles and Its Sulphenylation. J. Org. Chem. 2015;80(16):8217–8224. doi: 10.1021/acs.joc.5b01280. [DOI] [PubMed] [Google Scholar]
  32. Wei Y., Liu P., Liu Y., He J., Li X., Li S., Zhao J.. NIS-Promoted Three-Component Reaction of 3-Oxo-3-Arylpropanenitriles with Arylsulfonyl Hydrazides. Org. Biomol. Chem. 2021;19(17):3932–3939. doi: 10.1039/D1OB00438G. [DOI] [PubMed] [Google Scholar]
  33. Ogodo U. P., Abosede O. O.. The Role of Chemistry in Achieving Sustainable Development Goals: Green Chemistry Perspective. Int. Res. J. Pure Appl. Chem. 2025;26(1):1–8. doi: 10.9734/irjpac/2025/v26i1893. [DOI] [Google Scholar]
  34. Anastas P. T., Nolasco M. A., Kerton F. M., Kirchhoff M., Licence P., Pradeep T., Subramaniam B., Moores A.. The Power of the United Nations Sustainable Development Goals in Sustainable Chemistry and Engineering Research. ACS Sustainable Chem. Eng. 2021;9(24):8015–8017. doi: 10.1021/acssuschemeng.1c03762. [DOI] [Google Scholar]
  35. Tong W., Gao H., Yao W., Liu J., Wan J.-P.. Construction of α-Acyl-β-Amino Amides via Multicomponent Reactions of β-Acyloxy Alkenyl Amides with Amines and Aldehydes. Org. Lett. 2026;28(13):4234–4239. doi: 10.1021/acs.orglett.6c00813. [DOI] [PubMed] [Google Scholar]
  36. Cao S., Guo H., Zhong Z., Chen D., Song W., Liu Y., Wan J.-P.. β-Acyloxyl Alkenyl Amide Synthesis via Multiple Defluorination: α-Trifluoromethyl Ketone–Amine as Synergystic Peptide Coupling Reagent. Sci. Adv. 2025;11(43):eaea4120. doi: 10.1126/sciadv.aea4120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ye J., Li G., Wan C., Wan J.-P.. Chalcogen Functionalized Pyrimidine Synthesis by Three-Component Free Radical Chalcogenation and Pyrimidine Ring Construction. Org. Chem. Front. 2026;13(1):106–111. doi: 10.1039/D5QO01206F. [DOI] [Google Scholar]
  38. Acharya S. S., Guin B. K., Parida B. B.. One-Pot Multicomponent Synthesis of Fully Substituted 1,3-Thiazoles Appended with Naturally Occurring Lawsone. J. Org. Chem. 2025;90(7):2717–2727. doi: 10.1021/acs.joc.4c02927. [DOI] [PubMed] [Google Scholar]
  39. Cores Á., Clerigué J., Orocio-Rodríguez E., Menéndez J. C.. Multicomponent Reactions for the Synthesis of Active Pharmaceutical Ingredients. Pharmaceuticals. 2022;15(8):1009. doi: 10.3390/ph15081009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wang Z.-K., Wang L.-X., Lin H., Qiu B., Ma Y., Xiao J., An X.-D.. Visible-Light-Activated Photocatalyst- and Additive-Free Multi-Component Reaction Driven by the Cyclopropylamine-Based EDA Complex in Water. Green Chem. 2025;27(17):4565–4572. doi: 10.1039/D5GC00265F. [DOI] [Google Scholar]
  41. Renzi P., Scarfiello J., Lanfranco A., Deagostino A.. Light-Induced Domino and Multicomponent Reactions: How to Reach Molecular Complexity without a Catalyst. Eur. J. Org. Chem. 2023;26:e202300713. doi: 10.1002/ejoc.202300713. [DOI] [Google Scholar]
  42. Russo C., Graziani G., Cannalire R., Tron G. C., Giustiniano M.. Visible-Light Photocatalytic Metal-Free Multicomponent Ugi-like Chemistry. Green Chem. 2022;24(10):3993–4003. doi: 10.1039/D2GC00855F. [DOI] [Google Scholar]
  43. Sikdar P., Choudhuri T., Paul S., Das S., Kumar A., Bagdi A. K.. Photocatalyst-Free Visible-Light-Promoted C–H Selenylation of Pyrazolo­[1,5-a]­Pyrimidines. Synthesis. 2023;55(21):3693–3699. doi: 10.1055/a-2124-5485. [DOI] [Google Scholar]
  44. Lemir I. D., Castro-Godoy W. D., Heredia A. A., Schmidt L. C., Argüello J. E.. Metal- and Photocatalyst-Free Synthesis of 3-Selenylindoles and Asymmetric Diarylselenides Promoted by Visible Light. RSC Adv. 2019;9(39):22685–22694. doi: 10.1039/C9RA03642C. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Peglow T. J., Thomaz J. P. S. S. C., Gomes L. S., Nascimento V.. Potassium Persulfate Promoted the One-Pot and Selective Se -Functionalization of Pyrazoles under Acidic Conditions. ACS Omega. 2024;9(52):51295–51305. doi: 10.1021/acsomega.4c08079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wang X., Guo J., Xue S., Wang Z., Zhao J.. Visible-Light-Mediated Selenocyclization of o -Vinylanilides with Diselenides. Org. Biomol. Chem. 2025;23(7):1602–1606. doi: 10.1039/D4OB01898B. [DOI] [PubMed] [Google Scholar]
  47. Liu C., Xia J., Ji S., Fan Z., Xu H.. Visible-Light-Induced Metathesis Reaction between Diselenide and Ditelluride. Chem. Commun. 2019;55(19):2813–2816. doi: 10.1039/C9CC00252A. [DOI] [PubMed] [Google Scholar]
  48. Ji S., Cao W., Yu Y., Xu H.. Dynamic Diselenide Bonds: Exchange Reaction Induced by Visible Light without Catalysis. Angew. Chem., Int. Ed. 2014;53(26):6781–6785. doi: 10.1002/anie.201403442. [DOI] [PubMed] [Google Scholar]
  49. Singh D. K., Kumar R.. Clauson–Kaas Pyrrole Synthesis Using Diverse Catalysts: A Transition from Conventional to Greener Approach. Beilstein J. Org. Chem. 2023;19:928–955. doi: 10.3762/bjoc.19.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Singh P., Singh A., Singh D. K., Nath M.. Applications of Clauson-Kaas Reaction in Organic Synthesis. Chem. Rec. 2024;24(11):e202400112. doi: 10.1002/tcr.202400112. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

jo6c00605_si_001.pdf (3MB, pdf)

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information. Copies of (1H and 13C) NMR spectra of the compounds.

Articles from The Journal of Organic Chemistry are provided here courtesy of American Chemical Society

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