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Synthesis 2023; 55(21): 3693-3699
DOI: 10.1055/a-2124-5485
special topic
C–H Bond Functionalization of Heterocycles

Photocatalyst-Free Visible-Light-Promoted C–H Selenylation of Pyrazolo[1,5-a]pyrimidines

Papiya Sikdar
a   Department of Chemistry, University of Kalyani, Kalyani, W. B. 741235, India
,
Tathagata Choudhuri
a   Department of Chemistry, University of Kalyani, Kalyani, W. B. 741235, India
,
Suvam Paul
a   Department of Chemistry, University of Kalyani, Kalyani, W. B. 741235, India
,
Sourav Das
a   Department of Chemistry, University of Kalyani, Kalyani, W. B. 741235, India
,
Anil Kumar
b   Department of Chemistry, Birla Institute of Technology and Science Pilani, Pilani, Rajasthan 333031, India
,
Avik Kumar Bagdi  ∗
a   Department of Chemistry, University of Kalyani, Kalyani, W. B. 741235, India
› Author Affiliations

A.K.B. acknowledges the SERB, DST (File no. EEQ/2018/000498) and University of Kalyani (PRG) for financial support. P.S. acknowledges Govt. of West Bengal for her SVMCM Fellowship. T.C. (URS) acknowledges the University of Kalyani for his fellowship. S.P. (CSIR-JRF) and S.D. (UGC-JRF) acknowledge the CSIR-New Delhi and UGC-New Delhi for their fellowships. The authors also acknowledge DST New Delhi for HRMS Facility at BITS Pilani, Pilani Campus under FIST scheme (SR/FST/CSI-270/2015).
› Further Information
 
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Abstract

A new method has been developed for the C–H selenyl­ation of pyrazolo[1,5-a]pyrimidine derivatives under the irradiation of visible light. This photocatalyst-free strategy is applicable to a wide range of pyrazolo[1,5-a]pyrimidines with broad functionalities. The salient features of the method are mild reaction conditions, use of bench-stable oxidant, high regioselectivity, and scalability.


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Key words

photocatalyst-free - C–H selenylation - pyrazolo[1,5-a]pyrimidine - persulfate - visible light

Pyrazolo[1,5-a]pyrimidine derivatives, an important class of fused heterocycles exhibit various biological activities like antiviral, antifungal, anti-inflammatory, antibacterial, antiobesity, etc.[1] A number of commercially available agrochemicals and pharmaceuticals such as indiplon, lorediplon and zaleplon (hypnotic), ocinaplon (anxiolytic), reversan (anticancer), pyrazophos (fungicide), etc. contain pyrazolo[1,5-a]pyrimidine as the core structure (Figure [1]).[2] Some of these derivatives are also very useful in material science.[3] As a consequence, the synthesis of functionalized pyrazolo[1,5-a]pyrimidines is always highly important.[4]

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Figure 1 Pyrazolo[1,5-a]pyrimidine containing marketed drugs and pesticide

Synthesis of selenylated organic compounds are very important due to their wide importance in pharmaceuticals, material science, and organometallics.[5] These derivatives are generally prepared through selenylation using diselenides as selenylating agents.[6] Various transition-metal-catalyzed and iodine-catalyzed transformations have been employed for this reaction.[7] [8] Recently, visible-light-induced C–H selenylation has attracted attention of the synthetic chemists due to employment of renewable energy resources and atom-efficient pathway.[9] Ru-, Ir-, and organo-photocatalysts have been successfully employed in these light-induced C–H selenylation.[10] Only a few methods have been reported for the selenylation under photocatalyst-free conditions.[11] Arylselenyl radical could be easily generated from diaryl diselenide with the aid of persulfate as oxidant.[12] On the other hand, persulfate can be activated under the irradiation of visible light.[13] So, visible light induced generation of arylselenyl radical may be accelerated using persulfate as an oxidant. In continuation of our research interest on visible-light-induced C–H functionalization reaction,[14] we have successfully employed this strategy for the C–H selenylation of pyrazolo[1,5-a]pyrimidines by using K2S2O8 as an oxidant in DMSO under the irradiation of 23 W white LED at room temperature (Scheme [1]).

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Scheme 1 Visible-light-induced selenylation of pyrazolo[1,5-a]pyrimidines

The optimization of the reaction conditions for the C–H selenylation was initiated by selecting 2-methyl-7-phenylpyrazolo[1,5-a]pyrimidine (1a) as the model substrate. At the outset, the reaction of 1a with diphenyl diselenide (2a) as selenylating agent was carried out using (NH4)2S2O8 as an oxidant in DMSO as solvent under the irradiation of blue LED in the absence of any photocatalyst (Table [1], entry 1). Gratifyingly, the expected 2-methyl-7-phenyl-3-(phenylselanyl)pyrazolo[1,5-a]pyrimidine (3a) was obtained in 50% yield. This observation under photocatalyst-free conditions prompted us to investigate for further improvement of the yield of the desired product. The screening of other persulfates like Na2S2O8 and K2S2O8 as well as oxidants like PIDA, TBHP, and oxygen revealed that K2S2O8 was the most efficient for this transformation (entries 2–6). In the absence of any oxidant, the formation of selenylated product was observed albeit in much lower yield (entry 7). Among various solvents like DMSO, MeCN, 1,2-DCE, DMF, H2O, MeOH, EtOH, etc., DMSO was proven to be the best solvent for this reaction (entries 3 and 8–13). On increasing the loading of K2S2O8 to 1.2 equivalents increased the yield up to 78% (entry 14) whereas decreasing the oxidant loading was not beneficial (entries 15–17). Much better result was observed by carrying out the reaction under the irradiation of 23 W white LED (entry 18). On the other hand, very poor yield of product was obtained when the reaction were carried out in dark conditions (entry 19). So, the use of 1.2 equivalents of K2S2O8 as an oxidant in DMSO as solvent under the irradiation of 23 W white LED at room temperature (entry 18) was considered as optimized conditions for further studies.

Table 1 Optimization of the Reaction Conditionsa

Entry

Oxidant (equiv.)

Solvent

Light source

Yield (%)b

 1

(NH4)2S2O8 (1)

DMSO

Blue LED

50

 2

Na2S2O8 (1)

DMSO

Blue LED

48

 3

K2S2O8 (1)

DMSO

Blue LED

72

 4

PIDA (1)

DMSO

Blue LED

30

 5

TBHP (1)

DMSO

Blue LED

45

 6

Oxygen

DMSO

Blue LED

33

 7

–

DMSO

Blue LED

18

 8

K2S2O8 (1)

MeCN

Blue LED

70

 9

K2S2O8 (1)

1,2-DCE

Blue LED

44

10

K2S2O8 (1)

DMF

Blue LED

50

11

K2S2O8 (1)

H2O

Blue LED

28

12

K2S2O8 (1)

MeOH

Blue LED

35

13

K2S2O8 (1)

EtOH

Blue LED

37

14

K2S2O8 (1.2)

DMSO

Blue LED

78

15

K2S2O8 (0.2)

DMSO

Blue LED

45

16

K2S2O8 (0.5)

DMSO

Blue LED

63

17c

K2S2O8 (0.5)

DMSO

Blue LED

66

18d

K2S2O8 (1.2)

DMSO

White LED

81

19e

K2S2O8 (1.2)

DMSO

–

20

a Reaction conditions: A mixture of 1a (0.2 mmol), 2a (0.12 mmol), and oxidant in solvent (1 mL) under the irradiation of blue LED for 20 h.

b Isolated yields.

c In the presence of oxygen balloon.

d Under the irradiation of white LED.

e In the dark.

Next we investigated the substrate scope of this photocatalyst-free selenylation (Scheme [2]). Initially, various 7-aryl-2-methylpyrazolo[1,5-a]pyrimidines with electron-donating as well as electron-withdrawing substituents (Me, OMe, F, Cl, Br, NO2, etc.) present on the 7-phenyl ring were screened and delightfully the selenylated products 3a–g were obtained in good to excellent yields. 7-Naphthyl-substituted 2-methylpyrazolo[1,5-a]pyrimidines efficiently produced the respective selenylated products 3h and 3i in 80 and 81% yield. 7-Heteroaryl-substituted pyrazolo[1,5-a]pyrimidines also worked well to afford the selenylated products 3j and 3k in good yields (70 and 74%). Selenylation in these substrates took place regioselectively on the pyrazole ring. Under the optimized reaction conditions, 2-methyl-5,7-diphenylpyrazolo[1,5-a]pyrimidine, 2,5,7-tri­methylpyrazolo[1,5-a]pyrimidine, and 2,7-diphenyl pyrazolo[1,5-a]pyrimidine afforded the C3-selenylated product 3l, 3m, and 3n in 77, 70 and 79% yield, respectively.

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Scheme 2 Substrate scope for pyrazolo[1,5-a]pyrimidines. Reagents and conditions: A mixture of 1 (0.2 mmol), 2a (0.12 mmol), K2S2O8 (1.2 equiv.) in DMSO (1 mL) under the irradiation of a 23 W white LED for 20 h. Isolated yields are shown.

This selenylation strategy was also investigated for other diaryl diselenides with functionalities such as Me, OMe, and Br and satisfyingly the desired products 3o–q were obtained in good yields (Scheme [3]). Dithiophenyl diselenide efficiently produced the diheteroaryl selenide 3r in 64% yield. The investigation showed that the employment of dibenzyl diselenide and dimethyl diselenide as selenylating agent was also effective for the selenylation of pyrazolo[1,5-a]pyrimidine (3s and 3t). Further, sulfenylation of pyrazolo[1,5-a]pyrimidine could also be carried out employing this photocatalyst-free conditions using diphenyl disulfide as the sulfenylating agent; however, 20 mol% KI is necessary to obtain the sulfenylated product 3u.

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Scheme 3 Substrate scope for diselenides. Reagents and conditions: A mixture of 1a (0.2 mmol), 2 (0.12 mmol), K2S2O8 (1.2 equiv.) in DMSO under the irradiation of a 23 W white LED for 20 h. Isolated yields are shown. a 0.5 equiv. K2S2O8 was used. b Reaction time: 4 h. c 20 mol% KI was added and stirred for 3 h.

The regioselectivity of the methodology was also demonstrated (Scheme [4]). The employment of 3-substituted pyrazolo[1,5-a]pyrimidine (1o) under the optimized reaction conditions was not beneficial whereas only monoselenylation took place at 3-position producing 3v in 66% yield when 7-phenyl pyrazolo[1,5-a]pyrimidine (1p) was employed. Thus, the selenylation is highly regioselective towards C3-position. The methodology was applied on 5 mmol scale and good result (yield: 1.37 g, 75%) was obtained under simple reaction set-up.

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Scheme 4 Regioselectivity of selenylation strategy and large-scale synthesis
Zoom Image
Scheme 5 Controlled experiment and probable mechanistic pathway

Significant reduction in the yield of 3a was observed when the reaction of 1a and 2a was performed under optimized reaction conditions in the presence of TEMPO (Scheme [5]), indicating that the reaction proceeds through a radical pathway. Based on this control experiment and literature reports,[9] [12a] [13a] a probable mechanism of the selenylation is presented in Scheme [5]. It is well known that diselenides absorb visible light and are capable to form phenylselenyl radical both in the presence and absence of photocatalyst.[9] Initially, the phenylselenyl radical I is formed in the presence of K2S2O8 under the irradiation of white LED.[12a] [13a] Addition of phenylselenyl radical I at C3-position of pyrazolo[1,5-a]pyrimidine affords the radical intermediate II, which on oxidation affords the cationic intermediate III. Finally, elimination of proton from the intermediate III affords the desired product 3a. The intermediates II and III get stabilized due to the presence of two N-centers at the adjacent position. As a consequence, the methodology exhibits high regioselectivity for 3-selenylation.

In conclusion, we have developed a photocatalyst-free method for the selenylation of pyrazolo[1,5-a]pyrimidine derivatives. The activation of persulfate has been carried out under the irradiation of visible light without the aid of any photocatalyst. A library of 3-selenylated pyrazolo[1,5-a]pyrimidines has been synthesized employing this simple protocol. The use of visible light as energy source, wide functional group compatibility, scalability are the attractive features of this C–H selenylation.

All the reactants, reagents, and solvents were purchased from commercial sources Avra chemicals, Spectrochem, TCI, Merck, Sigma-Aldrich, etc. and used as received. Generally, the reactions were carried out in aerobic conditions employing oven-dried reaction vials under the irradiation of a white LED (23 W, brought from Philips) with a cooling fan. Reactions under blue LED irradiation were performed using blue LED strips. The temperature of the reaction medium was maintained at 28–30 °C. TLC was done on silica gel-coated glass slide (Merck, Silica gel G for TLC). Column chromatography was done using silica gel (100–200 mesh, Spectrochem, India) and mixture of EtOAc/ petroleum ether (PE) as an eluent. 1H and 13C NMR were recorded in 400 and 100 MHz, respectively, using Bruker NMR spectrometer in CDCl3. Chemical shifts are expressed in parts per million (δ) and the signals are reported as s (singlet), d (doublet), t (triplet), m (multiplet). Coupling constants J were given in Hz. HRMS of the purified compounds were done in 6545 Q-TOF LC/MS, Agilent.


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Selenylation of Pyrazolo[1,5-a]pyrimidines; General Procedure

In an oven-dried reaction vial containing 1 (0.2 mmol) and 2 (0.12 mmol) DMSO (1 mL) was added followed by K2S2O8 (0.065 g, 1.2 equiv.). The contents of the reaction vial were stirred under the irradiation of white LED (23 W) at rt for 20 h. After completion of the reaction (monitored by TLC), the reaction mixture was extracted with DCM/H2O. Then the extracted organic part was dried (anhyd Na2SO4) and evaporated to obtain the crude product. The crude product was purified by column chromatography using 100–200 mesh silica gel and a mixture of EtOAc/PE as an eluent.


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2-Methyl-7-phenyl-3-(phenylselanyl)pyrazolo[1,5-a]pyrimidine (3a)

Yield: 0.059 g (81%); yellow solid; mp 121–123 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.59 (d, J = 4.4 Hz, 1 H), 8.08–8.06 (m, 2 H), 7.59–7.57 (m, 3 H), 7.26–7.24 (m, 2 H), 7.15–7.13 (m, 3 H), 6.93 (d, J = 4.4 Hz, 1 H), 2.55 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 159.5, 151.8, 150.5, 146.9, 132.9, 131.3, 130.6, 129.4, 129.1, 129.0, 128.7, 126.0, 107.9, 92.1, 14.1.

HRMS: m/z calcd for C19H16N3Se [M + H]+: 366.0504; found: 366.0498.


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2-Methyl-3-(phenylselanyl)-7-(p-tolyl)pyrazolo[1,5-a]pyrimidine (3b)

Yield: 0.062 g (82%); yellow solid; mp 100–103 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.57 (d, J = 4.4 Hz, 1 H), 7.99 (d, J = 8.0 Hz, 2 H), 7.38 (d, J = 8.0 Hz, 2 H), 7.26–7.23 (m, 2 H), 7.15–7.13 (m, 3 H), 6.91 (d, J = 4.4 Hz, 1 H), 2.55 (s, 3 H), 2.46 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 159.4, 151.9, 150.4, 147.1, 141.8, 132.9, 129.4, 129.3, 129.0, 128.9, 127.7, 125.9, 107.5, 91.9, 21.6, 14.1.

HRMS: m/z calcd for C20H18N3Se [M + H]+: 380.0660; found: 380.0651.


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7-(4-Methoxyphenyl)-2-methyl-3-(phenylselanyl)pyrazolo[1,5-a]pyrimidine (3c)

Yield: 0.066 g (84%); brownish yellow solid; mp 96–98 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.55 (d, J = 4.4 Hz, 1 H), 8.13–8.10 (m, 2 H), 7.26–7.23 (m, 2 H), 7.16–7.07 (m, 5 H), 6.91 (d, J = 4.4 Hz, 1 H), 3.91 (s, 3 H), 2.56 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 161.9, 159.3, 151.9, 150.4, 146.7, 132.9, 131.2, 129.0, 128.9, 125.9, 122.7, 114.2, 107.1, 91.8, 55.5, 14.1.

HRMS: m/z calcd for C20H18N3OSe [M + H]+: 396.0610; found: 396.0604.


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7-(4-Fluorophenyl)-2-methyl-3-(phenylselanyl)pyrazolo[1,5-a]pyrimidine (3d)

Yield: 0.059 g (78%); pale yellow solid; mp 101–103 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.58 (d, J = 4.4 Hz, 1 H), 8.14–8.10 (m, 2 H), 7.29–7.23 (m, 4 H), 7.15–7.11 (m, 3 H), 6.90 (d, J = 4.4 Hz, 1 H), 2.55 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 164.4 (J C,F = 262 Hz), 159.7, 151.8, 150.4, 145.8, 132.7, 131.7 (J C,F = 9 Hz), 129, 126.7, 126.6 (J C,F = 3 Hz), 126, 116 (J C,F = 22 Hz), 107.6, 92.3, 14.0.

HRMS: m/z calcd for C19H15FN3Se [M + H]+: 384.0410; found: 384.0408.


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7-(4-Chlorophenyl)-2-methyl-3-(phenylselanyl)pyrazolo[1,5-a]pyrimidine (3e)

Yield: 0.061 g (77%); pale yellow solid; mp 98–100 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.59 (d, J = 4.4 Hz, 1 H), 8.05 (d, J = 8.4 Hz, 2 H), 7.55 (d, J = 8.8 Hz, 2 H), 7.26–7.23 (m, 2 H), 7.15–7.13 (m, 3 H), 6.91 (d, J = 4.4 Hz, 1 H), 2.55 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 159.6, 151.8, 150.4, 145.7, 137.5, 132.7, 130.8, 129.1, 128.9, 126.0, 107.7, 92.4, 14.0.

HRMS: m/z calcd for C19H15ClN3Se [M + H]+: 400.0114; found: 400.0112.


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7-(4-Bromophenyl)-2-methyl-3-(phenylselanyl)pyrazolo[1,5-a]pyrimidine (3f)

Yield: 0.066 g (75%); yellow solid; mp 98–101 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.59 (d, J = 4.4 Hz, 1 H), 7.98–7.96 (m, 2 H), 7.73–7.71 (m, 2 H), 7.26–7.24 (m, 2 H), 7.16–7.13 (m, 3 H), 6.92 (d, J = 4.4 Hz, 1 H), 2.55 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 159.6, 151.8, 150.4, 145.8, 132.7, 132.0, 130.9, 129.4, 129.1, 129.0, 126.0, 125.9, 107.6, 92.5, 14.0.

HRMS: m/z calcd for C19H15BrN3Se [M + H]+: 443.9609; found: 443.9599.


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2-Methyl-7-(3-nitrophenyl)-3-(phenylselanyl)pyrazolo[1,5-a]pyrimidine (3g)

Yield: 0.057 g (70%); brown solid; mp 97–100 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.97 (t, J = 2 Hz, 1 H), 8.66 (d, J = 4.4 Hz, 1 H), 8.46–8.43 (m, 2 H), 7.80 (t, J = 8 Hz, 1 H), 7.28–7.26 (m, 2 H), 7.17–7.15 (m, 3 H), 7.01 (d, J = 4 Hz, 1 H), 2.56 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 159.9, 151.7, 150.4, 148.3, 144.1, 135.2, 132.4, 132.2, 129.9, 129.2, 129.1, 126.2, 125.8, 124.6, 108.0, 93.2, 14.0.

HRMS: m/z calcd for C19H15N4O2Se [M + H]+: 411.0355; found: 411.0353.


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2-Methyl-7-(naphthalen-1-yl)-3-(phenylselanyl)pyrazolo[1,5-a]pyrimidine (3h)

Yield: 0.066 g (80%); yellow solid; mp 172–174 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.65 (d, J = 4.4 Hz, 1 H), 8.06 (d, J = 8.0 Hz, 1 H), 7.96 (d, J = 8.4 Hz, 1 H), 7.77–7.50 (m, 1 H), 7.65–7.62 (m, 1 H), 7.55–7.54 (m, 1 H), 7.44 (d, J = 3.6 Hz, 2 H), 7.31–7.28 (m, 2 H), 7.12–7.13 (m, 3 H), 6.93 (d, J = 4 Hz, 1 H), 2.44 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 159.7, 151.6, 150.2, 146.7, 133.6, 132.8, 131.2, 130.6, 129.2, 129.1, 128.7, 128.6, 128.1, 127.1, 126.6, 126.1, 125.2, 125.0, 110.3, 92.3, 14.1.

HRMS: m/z calcd for C23H18N3Se [M + H]+: 416.0660; found: 416.0656.


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2-Methyl-7-(naphthalen-2-yl)-3-(phenylselanyl)pyrazolo[1,5-a]pyrimidine (3i)

Yield: 0.067 g (81%); yellow gummy mass.

1H NMR (CDCl3, 400 MHz): δ = 8.63 (d, J = 4.0 Hz, 2 H), 8.12–8.09 (m, 1 H), 8.04–7.98 (m, 2 H), 7.94–7.92 (m, 1 H), 7.63–7.56 (m, 2 H), 7.28–7.25 (m, 2 H), 7.19–7.12 (m, 3 H), 7.05 (d, J = 4.4 Hz, 1 H), 2.57 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 159.6, 151.9, 150.4, 147.0, 134.5, 132.9, 130.1, 129.1, 129.0, 128.9, 128.4, 128.0, 127.9, 127.8, 126.9, 126.0, 125.6, 108.2, 92.2, 14.1.

HRMS: m/z calcd for C23H18N3Se [M + H]+: 416.0660; found: 416.0672.


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2-Methyl-3-(phenylselanyl)-7-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine (3j)

Yield: 0.051 g (70%); pale yellow solid; mp 97–99 °C.

1H NMR (CDCl3, 400 MHz): δ = 9.08 (d, J = 8.0 Hz, 1 H), 8.84–8.83 (m, 1 H), 8.69 (d, J = 4.4 Hz, 1 H), 7.98–7.94 (m, 1 H), 7.72 (d, J = 4.4 Hz, 1 H), 7.50–7.47 (m, 1 H), 7.26–7.23 (m, 2 H), 7.18–7.12 (m, 3 H), 2.60 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 159.3, 152.1, 150.5, 150.1, 148.1, 144.4, 136.7, 132.8, 129.1, 129.0, 126.2, 126.0, 125.5, 108.4, 92.3, 14.1.

HRMS: m/z calcd for C18H15N4Se [M + H]+: 367.0456; found: 367.0455.


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7-(Furan-2-yl)-2-methyl-3-(phenylselanyl)pyrazolo[1,5-a]pyrimidine (3k)

Yield: 0.052 g (74%); brown solid; mp 146–148 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.57 (d, J = 4.4 Hz, 1 H), 8.27 (d, J = 3.6 Hz, 1 H), 7.71 (d, J = 0.8 Hz, 1 H), 7.34 (d, J = 4.8 Hz, 1 H), 7.26–7.21 (m, 2 H), 7.15–7.09 (m, 3 H), 6.72–6.71 (m, 1 H), 2.60 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 159.5, 151.5, 149.6, 145.8, 143.8, 135.9, 132.9, 129.0, 128.9, 125.9, 120.1, 113.1, 103.0, 91.9, 14.1.

HRMS: m/z calcd for C17H14N3OSe [M + H]+: 356.0297; found: 356.0294.


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2-Methyl-5,7-diphenyl-3-(phenylselanyl)pyrazolo[1,5-a]pyrimidine (3l)

Yield: 0.068 g (77%); pale yellow solid; mp 155–158 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.19–8.16 (m, 2 H), 8.11–8.08 (m, 2 H), 7.60–7.58 (m, 3 H), 7.49–7.48 (m, 3 H), 7.37 (s, 1 H), 7.35–7.33 (m, 2 H), 7.17–7.14 (m, 3 H), 2.54 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 159.6, 157.1, 151.7, 146.8, 137.2, 133.2, 131.2, 131.1, 130.5, 129.4, 129.4, 129.0, 128.9, 128.7, 127.5, 125.9, 105.4, 92.5, 14.2.

HRMS: m/z calcd for C25H20N3Se [M + H]+: 442.0817; found: 442.0822.


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2,5,7-Trimethyl-3-(phenylselanyl)pyrazolo[1,5-a]pyrimidine (3m)

Yield: 0.044 g (70%); white solid; mp 86–88 °C.

1H NMR (CDCl3, 400 MHz): δ = 7.20–7.18 (m, 2 H), 7.16–7.09 (m, 3 H), 6.59 (s, 1 H), 2.75 (s, 3 H), 2.59 (s, 3 H), 2.52 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 160.3, 158.9, 150.7, 145.3, 133.3, 128.9, 128.6, 125.7, 109.1, 90.4, 24.9, 16.9, 13.9.

HRMS: m/z calcd for C15H16N3Se [M + H]+: 318.0504; found: 318.0517.


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2,7-Diphenyl-3-(phenylselanyl)pyrazolo[1,5-a]pyrimidine (3n)

Yield: 0.067 g (79%); yellowish white solid; mp 119–121 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.64 (d, J = 4.4 Hz, 1 H), 8.19–8.16 (m, 2 H), 8.11–8.09 (m, 2 H), 7.60–7.57 (m, 3 H), 7.43–7.38 (m, 3 H), 7.29–7.25 (m, 2 H), 7.16–7.07 (m, 3 H), 7.03 (d, J = 4.0 Hz, 1 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 158.4, 152.8, 150.7, 147.1, 133.3, 132.7, 131.4, 130.4, 129.6, 129.1, 129.0, 128.9, 128.7, 128.3, 126.0, 108.6, 90.3.

HRMS: m/z calcd for C24H18N3Se [M + H]+: 428.0660; found: 428.0673.


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2-Methyl-7-phenyl-3-(p-tolylselanyl)pyrazolo[1,5-a]pyrimidine (3o)

Yield: 0.060 g (79%); yellow gummy mass.

1H NMR (CDCl3, 400 MHz): δ = 8.58 (d, J = 4.4 Hz, 1 H), 8.07–8.05 (m, 2 H), 7.58–7.56 (m, 3 H), 7.19 (d, J = 8.0 Hz, 2 H), 6.97 (d, J = 8.0 Hz, 2 H), 6.91 (d, J = 4.0 Hz, 1 H), 2.55 (s, 3 H), 2.24 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 159.4, 151.8, 150.3, 146.9, 135.9, 131.2, 130.7, 129.9, 129.6, 129.4, 128.9, 128.7, 107.8, 92.7, 20.9, 14.1.

HRMS: m/z calcd for C20H18N3Se [M + H]+: 380.0660; found: 380.0642.


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3-((4-Methoxyphenyl)selanyl)-2-methyl-7-phenylpyrazolo[1,5-a]pyrimidine (3p)

Yield: 0.061 g (78%); yellow gummy mass.

1H NMR (CDCl3, 400 MHz): δ = 8.58 (d, J = 4.4 Hz, 1 H), 8.04 (d, J = 7.2 Hz, 2 H), 7.56–7.54 (m, 3 H), 7.32 (d, J = 8 Hz, 2 H), 6.89 (d, J = 4.4 Hz, 1 H), 6.72 (d, J = 8 Hz, 2 H), 3.71 (s, 3 H), 2.55 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 159.1, 158.6, 151.6, 150.3, 146.8, 132.0, 131.2, 130.7, 129.4, 128.7, 122.7, 114.8, 107.8, 93.5, 55.2, 14.1.

HRMS: m/z calcd for C20H18N3OSe [M + H]+: 396.0610; found: 396.0588.


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3-((4-Bromophenyl)selanyl)-2-methyl-7-phenylpyrazolo[1,5-a]pyrimidine (3q)

Yield: 0.066 g (75%); white solid; mp 124–126 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.60 (d, J = 4.4 Hz, 1 H), 8.09–8.06 (m, 2 H), 7.60–7.58 (m, 3 H), 7.27–7.25 (m, 2 H), 7.11–7.09 (m, 2 H), 6.95 (d, J = 4.4 Hz, 1 H), 2.54 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 159.4, 151.8, 150.6, 147.1, 132.0, 131.9, 131.4, 130.6, 130.5, 129.4, 128.8, 119.9, 108.0, 91.7, 14.0.

HRMS: m/z calcd for C19H15BrN3Se [M + H]+: 443.9609; found: 443.9588.


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2-Methyl-7-phenyl-3-(thiophen-2-ylselanyl)pyrazolo[1,5-a]pyri­midine (3r)

Yield: 0.047 g (64%); white solid; mp 108–110 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.61 (d, J = 4.4 Hz, 1 H), 8.02–8.00 (m, 2 H), 7.56–7.54 (m, 3 H), 7.28–7.24 (m, 2 H), 6.90–6.88 (m, 2 H), 2.64 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 158.5, 151.2, 150.3, 146.8, 133.4, 131.2, 130.6, 129.5, 129.4, 129.3, 128.7, 127.7, 107.8, 95.0, 14.1.

HRMS: m/z calcd for C17H14N3SSe [M + H]+: 372.0068; found: 372.0041.


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3-(Benzylselanyl)-2-methyl-7-phenylpyrazolo[1,5-a]pyrimidine (3s)

Yield: 0.036 g (48%); yellow solid; mp 128–130 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.56 (d, J = 4.4 Hz, 1 H), 8.06–8.03 (m, 2 H), 7.58–7.56 (m, 3 H), 7.15–7.13 (m, 3 H), 7.04–7.01 (m, 2 H), 6.88 (d, J = 4.4 Hz, 1 H), 3.92 (s, 2 H), 2.19 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 159.6, 151.7, 149.8, 146.7, 139.2, 131.2, 130.8, 129.3, 128.8, 128.7, 128.2, 126.5, 107.5, 92.3, 32.1, 13.6.

HRMS: m/z calcd for C20H18N3Se [M + H]+: 380.0660; found: 380.0673.


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2-Methyl-3-(methylselanyl)-7-phenylpyrazolo[1,5-a]pyrimidine (3t)

Yield: 0.036 g (60%); brownish yellow solid; mp 61–64 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.56 (d, J = 4.4 Hz, 1 H), 8.05–8.02 (m, 2 H), 7.57–7.56 (m, 3 H), 6.87 (d, J = 4.4 Hz, 1 H), 2.61 (s, 3 H), 2.20 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 158.3, 151.1, 149.6, 146.7, 131.1, 130.8, 129.3, 128.7, 107.4, 93.3, 14.1, 8.9.

HRMS: m/z calcd for C14H14N3Se [M + H]+: 304.0347; found: 304.0369.


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2-Methyl-7-phenyl-3-(phenylthio)pyrazolo[1,5-a]pyrimidine (3u)

Yield: 0.055 g (87%); yellow crystalline solid; mp 125–127 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.58 (d, J = 4.4 Hz, 1 H), 8.08–8.06 (m, 2 H), 7.59–7.57 (m, 3 H), 7.19–7.16 (m, 2 H), 7.10–7.06 (m, 3 H), 6.94 (d, J = 4.4 Hz, 1 H), 2.52 (s, 3 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 159.5, 151.4, 150.6, 147.1, 138.1, 131.4, 130.5, 129.4, 128.8, 128.7, 126.0, 125.1, 108.1, 95.8, 13.2.

HRMS: m/z calcd for C19H16N3S [M + H]+: 318.1059; found: 318.1037.


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7-Phenyl-3-(phenylselanyl)pyrazolo[1,5-a]pyrimidine (3v)

Yield: 0.046 g (66%); yellow solid; mp 126–128 °C.

1H NMR (CDCl3, 400 MHz): δ = 8.66 (d, J = 4.4 Hz, 1 H), 8.33 (s, 1 H), 8.05–8.02 (m, 2 H), 7.61–7.57 (m, 3 H), 7.36–7.33 (m, 2 H), 7.19–7.13 (m, 3 H), 7.00 (d, J = 4.4 Hz, 1 H).

13C{H}NMR (CDCl3, 100 MHz): δ = 150.9, 150.8, 150.7, 147.6, 132.8, 131.4, 130.4, 129.6, 129.3, 129.1, 128.8, 126.3, 108.3, 92.6.

HRMS: m/z calcd for C18H14N3Se [M + H]+: 352.0347; found: 352.0355.


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Procedure for the Controlled Experiment

In an oven-dried reaction vial, 2-methyl-7-phenylpyrazolo[1,5-a]pyrimidine (1a; 0.042 g, 0.2 mmol) 1,2-diphenyldiselane (2a; 0.038 g, 0.12 mmol), and TEMPO (0.093 g, 0.6 mmol) were taken and DMSO (1 mL) was added. Then K2S2O8 (0.065 g, 1.2 equiv.) was added to the reaction vial. The contents of the reaction vial were then stirred under the irradiation of white LED (23 W) at rt for 20 h. The mixture was extracted with DCM/H2O and the extracted organic part was dried (anhyd Na2SO4) followed by evaporation to obtain the crude product. The crude product was purified by column chromatography using 100–200 mesh silica gel and a mixture of EtOAc/PE (1:33) as eluent.


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Conflict of Interest

The authors declare no conflict of interest.

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-2124-5485.
  • Supporting Information

Corresponding Author

Avik Kumar Bagdi
Department of Chemistry, University of Kalyani
Kalyani, W. B. 741235
India   

Publication History

Received: 10 April 2023

Accepted after revision: 06 July 2023

Accepted Manuscript online:
06 July 2023

Article published online:
21 August 2023

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Figure 1 Pyrazolo[1,5-a]pyrimidine containing marketed drugs and pesticide
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Scheme 1 Visible-light-induced selenylation of pyrazolo[1,5-a]pyrimidines
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Scheme 2 Substrate scope for pyrazolo[1,5-a]pyrimidines. Reagents and conditions: A mixture of 1 (0.2 mmol), 2a (0.12 mmol), K2S2O8 (1.2 equiv.) in DMSO (1 mL) under the irradiation of a 23 W white LED for 20 h. Isolated yields are shown.
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Scheme 3 Substrate scope for diselenides. Reagents and conditions: A mixture of 1a (0.2 mmol), 2 (0.12 mmol), K2S2O8 (1.2 equiv.) in DMSO under the irradiation of a 23 W white LED for 20 h. Isolated yields are shown. a 0.5 equiv. K2S2O8 was used. b Reaction time: 4 h. c 20 mol% KI was added and stirred for 3 h.
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Scheme 4 Regioselectivity of selenylation strategy and large-scale synthesis
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Scheme 5 Controlled experiment and probable mechanistic pathway