Startseite Regioselectivity in the reaction of 5-amino-3-anilino-1H-pyrazole-4-carbonitrile with cinnamonitriles and enaminones: Synthesis of functionally substituted pyrazolo[1,5-a]pyrimidine derivatives
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Regioselectivity in the reaction of 5-amino-3-anilino-1H-pyrazole-4-carbonitrile with cinnamonitriles and enaminones: Synthesis of functionally substituted pyrazolo[1,5-a]pyrimidine derivatives

  • Moustafa Sherif Moustafa , Ahmed Moukhtar Nour-Eldeen , Saleh Mohamed Al-Mousawi EMAIL logo , Afaf Abd El-Hameed , Michael Magdy und Kamal Usef Sadek EMAIL logo
Veröffentlicht/Copyright: 28. Januar 2022
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Green Processing and Synthesis
Aus der Zeitschrift Green Processing and Synthesis Band 11 Heft 1

Abstract

The development of efficient methods for the synthesis of polyfunctional N-heterocycles is an important area of research in organic and medicinal chemistry. Pyrazolo[1,5-a]pyrimidine derivatives are purine analogous of biomedical importance and have been extremely studied for their broad spectrum of biological activities. Recently, they have attracted great interest in materials science owing to their photophysical properties. 3(5)-Aminopyrazoles are extensively utilized in the synthesis of condensed heterocyclic systems, particularly pyrazolo[1,5-a]pyrimidines via the reaction with 1,3-biselectrophilic reagents. However, the information available in the literature provides little in the way of reasoning their cyclization, particularly the initial attack either by the exocyclic amino group or endocyclic nitrogen. Unfortunately, the relative nucleophilicity of exo- and endocyclic nitrogen atoms in 1-unsubstituted 3(5)-aminopyrazoles is not clear and contradicting. It has been found that other factors can modulate the regioselectivity rather than basicity or steric hindrance for both active sites. The reported studies in the structure–activity relationship revealed that pyrazolo[1,5-a]pyrimidines having a substitution at fifth, sixth, and seventh positions possess potent biological activities, especially those with an amino group at the seventh position. We here developed a regioselective, high yield synthesis of 7-amino-5-arylpyrazolo[1,5-a]pyrimidine-3,6-dicarbonitriles by the reaction of N-(5-amino-4-cyano-1H-pyrazole-3-yl)-benzamide with various cinnamonitriles and enaminones in pyridine at 120°C under controlled microwave heating conditions. All structures of newly synthesized compounds were established by analytical and spectral data as well as single-crystal diffraction and rationalized for their formation.

Keywords: multicomponent reaction; regioselectivity; 7-aminopyrazolo[1,5-a]pyrimidines; microwave heating; X-ray crystallography

1 Introduction

Heterocyclic compounds containing pyrazole scaffold signify a wide spectrum of pharmacological activities and constitute a common nucleus in a variety of biologically active compounds [1,2,3,4,5,6]. Pyrazolo[1,5-a]pyrimidines are potential molecules of interest [7] and have been reported to possess anticancer [8,9], antimicrobial [10,11], antiviral [12], antifungal [13], anti-inflammatory [14], as well as large range of activities [15,16,17,18,19]. Examples of pyrazolo[1,5-a]pyrimidine’s marketed drugs are illustrated in Figure 1.

Figure 1 Pyrazolo[1,5-a]pyrimidines marketed drugs.
Figure 1

Pyrazolo[1,5-a]pyrimidines marketed drugs.

In this regard, the nature of substituents at fifth, sixth, and seventh positions displayed a crucial role in their biological potency. It is worth mentioning that the presence of an amino group at the seventh position had an additional advantage to form hydrogen bonds with the hinger region of the receptor [20].

The nucleophilicity and reactivity of different active centers in 5-aminopyrazole scaffolds have received considerable interest over the years. Concerning nitrogen centers, several published articles argue that in some synthetic protocols ring nitrogen is the most nucleophilic center while the opposite is observed in others [21,22]. Many different factors such as the nature of the ring substituent, temperature, pressure, solvent, catalyst type as well as the type of reaction controlling either the kinetic or thermodynamic can be utilized to modulate the selectivity of several transformations.

It has been reported that the reaction of 4-unsubstituted 3(5)-aminopyrazoles with bidentate reagents relies on the participation of the exocyclic amino group with ring nitrogen forming pyrazolo[1,5-a]pyrimidines, pyrazolo[5,1-c]-1,2,4-triazines, pyrazolo[1,5-a]-1,3,5-triazines or the nucleophilic carbon located at C4 of the pyrazole ring leading to pyrazolo[3,4-b]pyridines [23,24,25]. Whereas, for C4-substituted 3(5)-aminopyrazoles, considerable attention is required for the synthesis of bicyclic fused pyrazoloazines. Cyclization is affected by the electronic nature, either electron-donating or electron-attracting, of C-4. For example, electron-donating moieties augment the reactivity of the ring nitrogen favoring its initial attack by the bidentate reagent. However, electron-attracting substituents favor the initial attack by the less sterically hindered NH2 group.

It has been reported that the nature of the solvents plays a crucial role in such regioselective cyclocondensation. Owing to the amphoteric nature of 3(5)-aminopyrazoles, a basic solvent generates a heterocyclic anion resulting from the deprotonation of acidic-pyrole-like ring nitrogen, which enhances its reactivity. However, the acidic medium favors the exocyclic attack via protonating of the ring affording a cationic nucleus [26,27].

Arguably, a thorough investigation to establish the chemistry and regioselectivity of 3(5)-aminopyrazoles leading to complex heterocyclic scaffolds has not been established. Nevertheless, in-depth studies will be beneficial to elucidate their reactivity, their behavior and versatility in different environments, leading to the formation of a diversity of azoloazines in order to develop efficient synthetic methodologies.

Interestingly, a wide range of chemical transformations has now been performed under controlled microwave heating conditions. As compared to conventional heating reactions, microwaves couple directly with the molecules of the entire reaction mixture. Importantly, microwave heating possesses several advantages such as spectacular acceleration of many reactions, higher yields, mild reaction conditions, and shorter reaction times [28,29]. Moreover, several reports postulate the existence of a microwave effect as a specific radiation effect rather than the thermal one to rationalize for rate acceleration, changes in the reactivity as well as selectivity [30,31]. Our aim was to use a variety of factors to control the regioselectivity in such reactions leading to 7-aminopyrazolo[1,5-a]pyrimidines.

2 Materials and methods

Aldehydes, malononitrile, dimethylformamide dimethylacetal, and ketones were of commercial grade, and Pyridine was of analytically pure grade; all were purchased from Aldrich and Merck companies. 1H NMR (600 MHz) and 13C NMR (150 MHz) spectra were recorded using a Bruker DPX instrument (δ ppm). Mass spectra were determined by using a VG Auto spec QMS 30 and MSg (AEI) spectrometer in the EI (70 eV) mode. Melting points were recorded in a Gallen Kamp melting point apparatus and are uncorrected. X-ray crystallography was performed by using a Rigaku Rapid II and Bruker X8 Prospector single crystal X-ray diffractometer. All reactions were monitored by TLC with toluene/acetone 10:5, 10:6 as an eluent and were carried out until the starting materials were completely consumed.

2.1 General procedure for the synthesis of 7-aminopyrazolo[1,5-a]pyrimidine derivatives 4a–f and 7-arylpyrazolo[1,5-a]derivatives 7a–d

A solution of compounds 1 (1 mmol), 2 (1 mmol), or 5 (1 mmol) in pyridine (10 mL) was heated under reflux in a Milestone Microwave Lab station at 120°C for 20 min. The solvent was removed under reduced pressure, and the solid formed was isolated by filtration and recrystallized utilizing an appropriate solvent (Table 1).

Table 1

Description of synthesized products 4a–f and 7a–d

Compound no. Solvent of recrystallization Color of the product Melting point (°C)
4a Ethanol Orange crystals 308–310 [33]
4b Ethanol-dioxane Reddish brown crystals >360
4c Ethanol Yellow crystals 318–320
4d Ethanol Brown crystals 310–312
4e Ethanol Yellow crystals 288–290
4f Ethanol Brown crystals 259–260
7a Ethanol-dioxane Brown crystals 238–240
7b Ethanol Yellow crystals 268–270
7c Ethanol Reddish brown crystals 270–272
7d Ethanol Orange crystals 168–170

2.2 7-Amino-5,2-diphenylpyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile (4a)

Yield: 0.309 g (92%); R f = 0.57 (toluene/acetone 10:5); 1H NMR (600 MHz, DMSO-d 6) δ 6.97 (1H, t, J = 6–6 Hz, Ar–H); 7.31 (2H, t, J = 7.8 Hz Ar–H); 7.56–7.59 (m, 3H, Ar–H); 7.84,7.85 (2H, dd, J = 3.3, 4.2 Hz, Ar–H); 7.95 (2H, d, J = 7.8 Hz, Ar–H); 9.02 (br, s, 2H, NH2, D2O exchangeable); 9.51 (s, 1H, NH, D2O exchangeable). 13C NMR (150 MHz, DMSO-d 6) δ = 62.76; 66.32; 70.20; 75.69; 113.32; 115.88; 118.19; 121.27; 128.38; 128.65; 128.67; 130.59; 136.67; 140.35; 149.48; 150.85; 155.63; 162.10. Analysis results for C20H13N7: C, 68.37; H, 3.73; N, 27.90; found: C, 68.22; H, 3.82; N, 27.88; EIMS (m/z): 351.01 [M+].

2.3 7-Amino-5-(4-nitrophenyl)-2-(phenylamino)pyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile (4b)

Yield: 0.356 g (90%); R f = 0.52 (toluene/acetone 10:5); 1H NMR (600 MHz, DMSO-d 6) δ 6.97 (1H, t, J = 6.6 Hz, Ar–H); 7.31 (2H, d, J = 1.2 Hz, Ar–H); 7.94 (2H, J = 7.8 Hz, Ar–H); 8.09 (2H, d, J = 9 Hz, Ar–H); 8.39 (2H, d, J = 8.4 Hz); 9.12 (br, s, 2H, NH2); 9.54 (s, 1H, NH). 13C NMR (150 MHz, DMSO-d 6) δ 66.34; 70.71; 76.11; 113.12; 115.49; 118.24; 121.36; 123.57; 128.68; 130.19; 140.28; 142.57; 148.48; 149.33; 150.72; 155.71; 159.99. Analysis results for C20H12N8O2: C, 60.60; H, 3.05; N, 28.27; found: C, 60.63; H, 3.12; N, 28.33; EIMS (m/z): 396.03 [M+].

2.4 7-Amino-5-(4-chlorophenyl)-2-(phenylamino)pyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile (4c)

Yield: 0.354 g (92%); R f = 0.75 (toluene/acetone 10:5); 1H NMR (600 MHz, DMSO-d 6) δ 6.97 (1H, t, J = 7.2 Hz, Ar–H); 7.31 (2H, t, J = 7.2 Hz, Ar–H); 7.64 (2H, d, J = 8.4 Hz, Ar–H); 7.87 (2H, d, J = 8.4 Hz, Ar–H); 7.95 (2H, d, J = 8.4 Hz, Ar–H); 9.03 (2H, br, s, NH2); 9.52 (1H, s, NH). 13C NMR (150 MHz, DMSO-d 6) δ 70.35; 75.68; 113.26; 115.78; 121.31; 128.52; 128.68; 130.53; 135.45; 140.33; 149.43; 150.79U; 155.65; 160.82. Analysis results for C20H12CLN7: C, 62.26; H, 3.14; Cl, 9.19; N, 25.41; found: C, 62.32; H, 3.18; Cl, 9.12; N, 25.58; EIMS (m/z) 385.12 [M+].

2.5 7-Amino-5-(4-methoxyphenyl)-2-(phenylamino)pyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile (4d)

Yield: 0.354 g (93%); 1H NMR (600 MHz, DMSO-d 6) δ 3.52 (3H, s, OCH3); 6.97 (1H, t, J = 7.2 Hz, Ar–H); 7.02–7.13 (2H, m, Ar–H); 7.03 (2H, t, J = 7.8 Hz, Ar–H); 7.85–7.88 (2H, m, Ar–H); 7.95 (2H, t, J = 6.6 Hz, Ar–H); 8.3 (2H, br, s, NH2); 9.48 (1H, s, NH); 13C NMR (150 MHz, DMSO-d 6) δ 55.39; 60.11; 76.8; 113.42; 113.76; 114.77; 115.13; 116.06; 116.17; 121.22; 124.07; 128.41; 128.65; 128.78; 130.42; 133.31; 140.38; 149.57, 150.83; 155.62; 160.39; 161.25; 161.37; 164.31. Analysis results for C21H15N6O: C, 66.13; H, 3.96; N, 25.71; found: C, 66.22; H, 4.01; N, 25.75; EIMS (m/z) 381.11 [M+]

2.6 7-Amino-5-(2-chlorophenyl)-2-(phenylamino)pyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile (4e)

Yield: 0.351 g (91%); 1H NMR (600 MHz, DMSO-d 6) δ 6.98 (1H, t, J = 7.8 Hz, Ar–H); 7.32 (2H, t, J = 7.8 Hz, Ar–H); 7.51 (1H, t, J = 7.2 Hz, Ar–H); 7.54 (2H, d, J = 1.8 Hz, Ar–H); 7.53 (2H, d, Ar–H); 7.565–7.592 (2H, m, Ar–H); 7.64–7.65 (1H, m, Ar–H); 7.95 (d, 2H, J = 7.8, Ar–H); 9.14 (2H, br, s, NH2); 9.565 (1H, s, NH), 13C NMR (150 MHz, DMSO-d 6) δ 66.35; 70.62; 78.16; 113.10; 114.66; 116.09; 118.24; 121.40; 127.41; 128.41; 128.58; 128.72; 129.56; 130.42; 131.07; 131.45; 136.24; 140.31; 148.62; 150.79; 155.64; 161.44. Analysis results for C20H12ClN7: C, 62.26; H, 3.14; Cl, 9.19; N, 25.41; found: C, 62.24; H, 3.21; Cl, 9.23; N, 25.39; EIMS (m/z): 385.03 [M+].

2.7 7-Amino-5-(3-bromophenyl-2-(phenylamino)pyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile (4f)

Yield: 0.386 g (90%); (toluene/acetone 10:5); 1H NMR (600 MHz, DMSO-d 6) δ 6.97 (1H, t, J = 7.2 Hz, Ar–H); 7.04 (2H, t, J = 7.2 Hz, Ar–H); 7.52, 7.54 (2H, dd, J = 4.2 and 7.8 Hz, Ar–H); 7.77 (1H, t, J = 1.2 Hz, Ar–H); 7.79 (1H, d, J = 1.2 Hz, Ar–H); 7.84 (1H, t, J = 6.6 Hz, Ar–H); 7.94 (2H, d, J = 7.8 Hz, Ar–H); 7.98 (1H, t, J = 1.8 Hz, Ar–H); 9.15 (2H, br, s, NH2); 9.53 (1H, S, NH). Analysis results for C20H12BrN4: C, 55.83; H, 2.81; Br, 18.57; N, 22.79; found: C, 55.88; H, 2.92; Br, 18.66; N, 22.52; EIMS (m/z): 429.01 [M+].

2.8 7-Phenyl-2-(phenylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (7a)

Yield: 0.286 g (92%); 1H NMR (600 MHz, DMSO-d 6) δ 6.94 (1H, t, J = 7.2 Hz, Ar–H); 7.26 (2H, t, J = 7.8 Hz, Ar–H); 7.34 (1H, d, J = 4.8 Hz, Ar–H); 7.60–7.62 (3H, m, Ar–H); 7.63 (3H, t, J = 2.4 Hz, Ar–H); 7.64–7.67 (3H, m, Ar–H); 8.12 (1H, d, J = 1.8 Hz, C5–H); 8.13 (1H, d, J = 1.2 Hz, Ar–H); 8.65 (1H, J = 4.8 Hz, C6-H); 9.59 (1H, s, NH); 13C NMR (150 MHz, DMSO-d 6) δ 66.3 67.89; 109.24; 113.47; 117.95; 121.39; 128.42; 128.6; 129.44; 129.74; 131.51; 140.48; 145.9; 151.78; 152.22; 155.91. Analysis results for C19H13N5: C, 73.30; H, 4.21; N, 22.49; found: C, 73.22; H, 4.31; N, 22.42; EIMS (m/z): 311.17 [M+].

2.9 7-(2-Nitrophenyl)-2-(phenylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (7b)

Yield: 0.320 g (90%); 1H NMR (600 MHz, DMSO-d 6) δ 6.90–6.93 (1H, m, Ar–H); 7.17–7.20 (2H, m, Ar–H); 7.39–7.41 (2H, m, Ar–H); 7.46 (1H, J = 4.8 Hz, Ar–H); 7.84–7.86 (1H, m, Ar–H); 7.94–7.97 (2H, m, Ar–H); 8.03–8.05 (1H, m, Ar–H); 8.39, 8.41 (1H, dd, J = 1.2, 1.2 Hz, C5–H); 8.79 (1H, J = 4.8 Hz, C6–H); 9.56 (1H, s, Ar–H); 13C NMR (150 MHz, DMSO-d 6) δ 68.12; 109.70; 113.06; 117.91; 117.99; 121.66; 124.63; 124.81; 128.49; 132.71; 134.98; 140.03; 144.57; 147.51; 150.51; 152.92; 156.09. Analysis results for C19H12N6O2: C, 64.04; H, 3.39; N, 23.58; found: C, 64.12; H, 4.01; N, 23.67; EIMS (m/z) 356.02 [M+].

2.10 7-(4-Methylphenyl)-2-(phenylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (7c)

Yield: 0.289 g (89%); (toluene/acetone 10:6); 1H NMR (400 MHz, DMSO-d 6) δ 2.38 (3H, s, CH3); 6.94–7.69 (9H, m, Ar–H); 8.10 (1H, d, J = 1.2 Hz, C5–H); 8.66 (1H, d, J = 4.8 Hz, C6–H); 9.59 (1H, s, NH). Analysis results for C20H15N5: C, 73.83; H, 4.65; N 21.52; found: C, 73.88; H, 4.62; N, 2155.

2.11 7-(4-Methoxyphenyl)-2-(phenylamino)pyrazolo[15-a]pyrimidine-3-carbonitrile (7d)

Yield: 0.307 g (88%); (toluene/acetone 10:6); 1H NMR (400 MHz, DMSO-d 6) δ 3.34 (3H, s, OCH3); 6.92–7.57 (9H, m, Ar–H); 8.13 (1H, d, J = 1.2 Hz, C5–H); 8.65 (1H, d, J = 4.8 Hz, C6–H); 9.85 (1H, s, NH). Analysis results for C20H15N5O: C, 70.37; H, 4.43; N, 20.52; found: C, 70.44; H, 4.42; N, 20.57.

3 Results and discussion

The reaction of N-(5-amino-4-cyano-1H-pyrazole-3-yl)-benzamide 1 with a variety of electrophiles was reported to afford different isomeric pyrazolo[1,5-a]pyrimidine derivatives. Thus, in an early report [32], the reaction of 1 with tetracyano ethylene in dry ethyl acetate or methylene chloride at ambient temperature for 48 h or with 2-(dicyanomethylene) indan-1, 3-dione (CNIND) in dry pyridine and heating under reflux at 100°C for 3 h afforded mainly the corresponding 5-aminopyrazolo [1,5-a]pyrimidine via the initial attachment of ring nitrogen followed by cyclization of the formed 1:1 adduct with an exocyclic amino group, which was subsequently supported by other authors. Soliman et al. [33] have similarly reported that reaction of 1 with various halo reagents, active methylenes, and ketene dithioacetals under phase transfer conditions proceeds via the initial attack of the endocyclic ring nitrogen at the electrophile active site followed by cyclization of the cyclic intermediate with the exocyclic amino group. However, they revealed the initial attack by the exocyclic amino group upon reacting 1 with acetyl chloride, ethoxymethylene, malononitrile, and Lawson’s reagent followed by cyclization with the ring nitrogen. A similar pathway was reported by Ahmed et al. [34] and Dozhenko et al. [35]. Elnagdi et al. [36,37] examined the regio-orientation in the reaction of 5-aminopyrazoles with benzylidene malononitrile and enaminones utilizing (15N, 1H) HMBC to establish a more conclusive structure elucidation as the structure assigned for such reactions was mainly based on 1H NMR and IR spectra. They concluded that the reaction with benzylidene malononitrile proceeds initially by the nucleophilic attack of the exocyclic amino group; however, the initial attack of the ring nitrogen occurs with enaminones. Moreover, under such basic reaction conditions, the cyano group at the C-4 pyrazole ring remained inactive. In contrast, Hebishy and co-workers [38] recently reported the reaction of N-(5-amino-4-cyano1H-pyrazol-3-yl)-benzamide with arylidinemalononitrile afforded the corresponding 5-aminopyrazolo[1,5-a]pyrimidine derivatives. Recently, the catalyst-free Biginelli-type reaction of 5-amino-3-arylpyrazole-4-carbonitriles with ylidene-1,3-dicarbonyl compounds by refluxing in DMF has been reported by Dotsenko and co-workers [39]. The authors confirmed the formation of the corresponding 4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitriles via the intermediacy of the aza-Michael adduct resulting from the initial attack of the ring nitrogen and subsequent cyclo-condensation with the exocyclic amino group. The reaction of 1 with dimedone catalyzed by tin(ii) chloride dehydrate, which acts as a Lewis acid, and a low melting solvent was recently reported to afford the corresponding pyrazolo[5,4–b]quinolones via the nucleophilic attack of the exocyclic amino group on the carbonyl carbon of dimedone followed by cyclization of the formed imino form on to the cyano group and hydrolysis [40]. A similar phenomenon was reported by Schmidtke and co-authors [41].

To shed further light on this unresolved issue and in continuation of our studies in which we utilize microwave heating [42,43,44,45,46,47,48], we report herein the results of our investigation on the reaction of N-(5-amino-4-cyano-1H-pyrazole-3-yl)-benzamide 1 with various electrophiles under controlled microwave heating conditions. Our aim was to modulate several factors controlling regioselectivity in such reactions.

The reaction of 5-aminopyrazole derivative 1 with benzylidene malononitrile 2a in pyridine under microwave irradiation (120°C, 20 min) was found to afford selectively the corresponding 7-aminopyrazolo[1,5-a]-pyrimidine derivative 4a rather than isomeric 5-aminopyrazole 3a. The mass spectrum of 4a showed a molecular ion peak m/z = 351.01 (100%). The IR spectra (KBr) showed an amino group, two cyano groups, and C═N absorption bands at λ max = 3,441, 3,360, 2,179, 2,200, and 1,631 cm−1. 1H NMR spectra revealed a broad singlet at δ = 9.02 ppm integrated for two protons, which was assigned to the NH2 group at C-7. If the reaction product was isomeric 5-amino derivatives, such amino groups will appear at a higher field shift. This low downfield shift could be rationalized for the anisotropic effect of the adjacent pyrazole ring nitrogen. In addition, it reveals signals at δ = 6.97 (1H, t, J = 6.6 Hz, Ar–H), 7.31 (2H, t, J = 7.8 Hz, Ar–H), 7.56–7.59 (m, 3H, Ar–H), 7.84–7.85 (2H, dd, J = 3.3, 4.2 Hz, Ar–H), 7.95 (2H, d, J = 7.8 Hz, Ar–H), 9.02 (1H, s, aniline-NH, D2O exchangeable). Its 13C NMR spectrum showed characteristic signals at δ = 75.69 (pyrazole C-3), 115.88 (CN at C-6), 118.19 (CN at C-3), 121.27–140-35 (aromatic carbons), 149.48 (C-4), 155.63 (C-5), 162.1 (C-7). Furthermore, the structure of 4a was unambiguously confirmed by single-crystal X-ray diffraction [41] (Figure 2).

Figure 2 ORTEB diagram of compound 4a (X-ray).
Figure 2

ORTEB diagram of compound 4a (X-ray).

With these results in hand, we investigated the scope of such reactions with a variety of substituted cinnamonitrile derivatives. Thus, the reaction of 1 with 2b–f under the same experimental conditions afforded the corresponding 7-aminopyrazolo [1,5-a]pyrimidine derivatives 4b–f, respectively, in excellent yields. The structures of 4b–f were established from their mass spectra, 1H NMR, and 13C NMR spectra, which showed a similar pattern as compound 4a as well as elemental analysis. Further confirmation was achieved by single-crystal X-ray diffraction of 4d [42] (Figure 3, Scheme 1). These results were in contrast to that reported for the formation of 5-aminopyrazolo[1,5-a]pyrimidines from the reaction of 1 with arylidenemalononitriles [37]

Figure 3 ORTEB diagram of compound 4d (X-ray).
Figure 3

ORTEB diagram of compound 4d (X-ray).

Scheme 1 The reaction of 5-aminopyrazole derivatives 1 with benzylidene malononitrile derivatives 2.
Scheme 1

The reaction of 5-aminopyrazole derivatives 1 with benzylidene malononitrile derivatives 2.

Another example of regioselectivity in the reaction of 5-aminopyrazoles with electrophilic reagents was reported [41] involving its reaction with (E)-3-(dimethylamino)-1-arylprop-2-en-1-one derivatives, which afforded the corresponding 5-arylpyrazolo[1,5-a]pyrimidines formed via the initial attack by the ring nitrogen. It is worth mentioning that such cyclocondensation is not favored in our case. Thus, the reaction of 1 with (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one 5a afforded the corresponding 7-arylpyrazolo[1,5-a]pyrimidine 7a. The possible formation of 5-arylpyrazolo[1,5-a]pyrimidine 6a was ruled out based on analytical and spectral data. The mass spectra showed a molecular ion peak m/z = 311.17 (43%). The 1H NMR revealed a downfield doublet at δ = 8.65 ppm and a doublet at δ = 8.13 ppm, corresponding to C6–H and C5–H and signals at δ = 6.94 (1H, t, J = 7.2 Hz, Ar–H), 7.26 (2H, t, J = 7.8 Hz, Ar–H), 7.34 (1H, d, J = 4.8 Hz, Ar–H), 7.60–7.62 (3H, m, Ar–H), 7.63 (3H, t, J = 2.4 HZ, Ar–H), 7.64–7.67 (3H, m, Ar–H), 8.13 (1H, d, J = 1.2, Ar–H), 9.59 (1H, s, aniline–NH). If the reaction product was 6a, the signal assigned for C6–H will appear at a higher field shift. The 13C NMR spectrum revealed C6 and C7-carbons at δ = 109.24 and 151.78, which are difficult to rationalize for if the product was 6a in addition to the characteristic signals at δ = 117.95 (CN at C-3), 113.47–140.48 (aromatic carbons), 145.9 (C-4), and 152.22 (C-2).

Moreover, the structure of 7a was confirmed by single-crystal X-ray diffraction (Figure 4) [43].

Figure 4 ORTEB diagram of compound 6a (X-ray).
Figure 4

ORTEB diagram of compound 6a (X-ray).

Similarly, compound 1 reacted with 5b under the same experimental conditions to afford the newly synthesized 7-arylpyrazolo[1,5-a]pyrimidines 7b–d (Scheme 2). The structure proposed for the reaction products was established based on a similar 1H NMR and 13NMR pattern as 7a

Scheme 2 The reaction of 5-aminopyrazole derivatives 1 with enaminone derivatives 5.
Scheme 2

The reaction of 5-aminopyrazole derivatives 1 with enaminone derivatives 5.

A proposed mechanism to account for the formation of 4a–g and 7a–d was demonstrated in Scheme 3. An initial attack of the exocyclic amino group on the activated double bond system in 2a–g afforded 1:1 adduct 10 followed by cyclization via the addition of the ring NH to the cyano group and subsequent aromatization. The same applies for the formation of 7a, which proceeds via dimethylamine elimination from the reaction of the exocyclic amino group with 5a forming intermediate 13 and subsequent cyclization via the attack of the lone pair at the carbonyl group of ring nitrogen with water loss.

Scheme 3 Mechanism of the formation of 4af and 7a–d.
Scheme 3

Mechanism of the formation of 4af and 7a–d.

4 Conclusion

In conclusion, we can reveal that ring nitrogen is the more basic center and the exocyclic amino group is the less hindered. An attack by ring nitrogen is favored with less sterically hindered electrophiles; however, the attack with the exocyclic amino group predominates with bulky electrophiles. However, no firm conclusion on which to determine the preferred tautomer form of the final product has been arrived. Here, we do believe that the nature of the substituents of the aminopyrazole scaffold plays a crucial role in such regioselectivity. The presence of a cyano group at C-4 in compound 1 reduces the donating ability of the ring nitrogen. Moreover, for the titled compound, the chains of dimers formed by pairs of ring N–H····N hydrogen bonds render it less active. We concluded that unambiguous assignment of the regioselectivity in such reactions requires advanced techniques, particularly X-ray diffraction crystallography as insufficient spectral data could be a mess resulting in incorrect conclusions.

Acknowledgments

Kamal U. Sadek is grateful to the Alexander von Humboldt Foundation for donating a milestone START Microwave Labstation. Saleh Al-Mousawi and Moustafa Sherif Moustafa are very grateful to the Kuwait Foundation for the Advancement of Science, project number PR1714SC02, and Kuwait University for general facilities projects GS01/03, GS01/05, and SG0308.

  1. Funding information: This study was funded by project no. PR1714SC02.

  2. Author contributions: Moustafa S. Moustafa: visualization and methodology; Ahmed M. Nour-Eldeen: formal analysis and data curation; Saleh M. Al-Mousawi: methodology, formal analysis; Afaf A. El-Hameed: writing – review and editing; Michael Magdy: writing – review and editing; Kamal U. Sadek: supervision and writing – original draft.

  3. Conflict of interest: The authors state no conflict of interest.

Appendix

Characterization data for compounds 4a, 4b, 4c, 4d, 4e, 4f, 7a, 7b, 7c, and 7d.

A1 7-Amino-5,2-diphenylpyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile (4a)

Orange crystals; mp: 308–310°C; yield: 0.309 g (92%); R f = 0.57 (toluene/acetone 10:5); 1H NMR (600 MHz, DMSO-d 6) δ 6.97 (1H, t, J = 6–6 Hz, Ar–H), 7.31 (2H, t, J = 7.8 Hz, 7.56–7.59) (m, 3H, Ar–H), 7.84, 7.85 (2H, dd, J = 3.3, 4.2 Hz, Ar–H), 7.95 (2H, d, J = 7.8 Hz, Ar–H), 9.02 (br, s, 2H, NH2, D2O exchangeable), 9.51 (S, 1H, NH, D2O exchangeable); 13C NMR (150 MHz, DMSO-d 6) δ = 62.76, 66.32, 70.20, 75.69, 113.32, 115.88, 118.19, 121.27, 128.38, 128.65, 128.67, 130.59, 136.67, 140.35, 149.48, 150.85, 155.63, 162.10. Analysis results for C20H13N7: C, 68.37; H, 3.73; N, 27.90; found: C, 68.22; H, 3.82; N, 27.88; EIMS (m/z): 351.01 [M+].

A2 7-Amino-5-(4-nitrophenyl)-2-(phenylamino)pyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile (4b)

Reddish brown crystals; mp: >360°C; yield: 0.356 g (90%); R f = 0.52 (toluene/acetone 10:5); 1H NMR (600 MHz, DMSO-d 6) δ 6.97 (1H, t, J = 6.6 Hz, Ar–H), 7.31 (2H, d, J = 1.2 Hz, Ar–H), 7.94 (2H, J = 7.8 Hz, Ar–H), 8.09 (2H, d, J = 9 Hz, Ar–H), 8.39 (2H, d, J = 8.4 Hz), 9.12 (br, s, 2H, NH2), 9.54 (s, 1H, NH), 13C NMR (150 MHz, DMSO-d 6) δ 66.34, 70.71, 76.11, 113.12, 115.49, 118.24, 121.36, 123.57, 128.68, 130.19, 140.28, 142.57, 148.48, 149.33, 150.72, 155.71, 159.99. Analysis results for C20H12N8O2: C, 60.60; H, 3.05; N, 28.27; found: C, 60.63; H, 3.12; N, 28.33; EIMS (m/z): 396.03 [M+].

A3 7-Amino-5-(4-chlorophenyl)-2-(phenylamino)pyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile (4c)

Yellow crystals; mp: 318–320°C; yield: 0.354 g (92%); R f = 0.75 (toluene/acetone 10:5); 1H NMR (600 MHz, DMSO-d 6) δ 6.97 (1H, t, J = 7.2 Hz, Ar–H), 7.31 (2H, t, J = 7.2 Hz, Ar–H), 7.64 (2H, d, J = 8.4 Hz, Ar–H), 7.87 (2H, d, J = 8.4 Hz, Ar–H), 7.95 (2H, d, J = 8.4 Hz, Ar–H), 9.03 (2H, br, s, NH2), 9.52 (1H, s, NH); 13C NMR (150 MHz, DMSO-d 6) δ 70.35, 75.68, 113.26, 115.78, 121.31, 128.52, 128.68, 130.53, 135.45, 140.33, 149.43, 150.79, 155.65, 160.82. Analysis results for C20H12CLN7: C, 62.26; H, 3.14; Cl, 9.19; N, 25.41; found: C, 62.32; H, 3.18; Cl, 9.12; N, 25.58; EIMS (m/z) 385.12 [M+]

A4 7-Amino-5-(4-methoxyphenyl)-2-(phenylamino)pyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile (4d)

Brown crystals; mp: 310–312°C; yield: 0.354 g (93%); 1H NMR (600 MHz, DMSO-d 6) δ 3.52 (3H, s, OCH3), 6.97 (1H, t, J = 7.2 Hz, Ar–H), 7.02–7.13 (2H, m, Ar–H), 7.03 (2H, t, J = 7.8 Hz, Ar–H), 7.85–7.88 (2H, m, Ar–H), 7.95 (2H, t, J = 6.6 Hz, Ar–H), 8.3 (2H, br, s, NH2), 9.48 (1H, s, NH); 13C NMR (150 MHz, DMSO-d 6) δ 55.39, 60.11, 76.8, 113.42, 113.76, 114.77, 115.13, 116.06, 116.17, 121.22, 124.07, 128.41, 128.65, 128.78, 130.42, 133.31, 140.38, 149.57, 150.83, 155.62, 160.39, 161.25, 161.37, 164.31. Analysis results for C21H15N6O: C, 66.13; H, 3.96; N, 25.71; found: C, 66.22; H, 4.01; N, 25.75; EIMS (m/z) 381.11 [M+].

A5 7-Amino-5-(2-chlorophenyl)-2-(phenylamino)pyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile (4e)

Yellow crystals; mp: 288–290°C; yield: 0.351 g (91%); 1H NMR (600 MHz, DMSO-d 6) δ 6.98 (1H, t, J = 7.8 Hz, Ar–H), 7.32 (2H, t, J = 7.8 Hz, Ar–H), 7.51 (1H, t, J = 7.2 Hz, Ar–H), 7.54 (2H, d, J = 1.8 Hz, Ar–H), 7.53 (2H, d, Ar–H), 7.565–7.592 (2H, m, Ar–H), 7.64–7.65 (1H, m, Ar–H), 7.95 (d, 2H, J = 7.8, Ar–H), 9.14 (2H, br, s, NH2), 9.565 (1H, s, NH), 13C NMR (150 MHz, DMSO-d 6) δ 66.35, 70.62, 78.16, 113.10, 114.66, 116.09, 118.24, 121.40, 127.41, 128.41, 128.58, 128.72, 129.56, 130.42, 131.07, 131.45, 136.24, 140.31, 148.62, 150.79, 155.64, 161.44. Analysis results for C20H12ClN7: C, 62.26; H, 3.14; Cl, 9.19; N, 25.41; found: C, 62.24; H, 3.21; Cl, 9.23; N, 25.39; EIMS (m/z): 385.03 [M+].

A6 7-Amino-5-(3-bromophenyl-2-(phenylamino)pyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile (4f)

Brown crystals; mp: 259–260°C; yield: 0.386 g (90%); (toluene/acetone 10:5); 1H NMR (600 MHz, DMSO-d 6) δ 6.97 (1H, t, J = 7.2 Hz, Ar–H), 7.04 (2H, t, J = 7.2 Hz, Ar–H); 7.52, 7.54 (2H, dd, J = 4.2 and 7.8 Hz, Ar–H), 7.77 (1H, t, J = 1.2 Hz, Ar–H), 7.79 (1H, d, J = 1.2 Hz, Ar–H), 7.84 (1H, t, J = 6.6 Hz, Ar–H), 7.94 (2H, d, J = 7.8 Hz, Ar–H), 7.98 (1H, t, J = 1.8 Hz, Ar–H), 9.15 (2H, br, s, NH2), 9.53 (1H, S, NH). Analysis results for C20H12BrN4: C, 55.83; H, 2.81; Br, 18.57; N, 22.79; found: C, 55.88; H, 2.92; Br, 18.66; N, 22.52; EIMS (m/z): 429.01 [M+].

A7 7-Phenyl-2-(phenylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (7a)

Brown crystals; mp: 238–240°C; yield: 0.286 g (92%); 1H NMR (600 MHz, DMSO-d 6) δ 6.94 (1H, t, J = 7.2 Hz, Ar–H); 7.26 (2H, t, J = 7.8 Hz, Ar–H), 7.34 (1H, d, J = 4.8 Hz, Ar–H), 7.60–7.62 (3H, m, Ar–H), 7.63 (3H, t, J = 2.4 Hz, Ar–H), 7.64–7.67 (3H, m, Ar–H), 8.12 (1H, d, J = 1.8 Hz, C5–H), 8.13 (1H, d, J = 1.2 Hz, Ar–H), 8.65 (1H, J = 4.8 Hz, C6–H), 9.59 (1H, s, NH); 13C NMR (150 MHz, DMSO-d 6) δ 66.3–67.89, 109.24, 113.47, 117.95, 121.39, 128.42, 128.6, 129.44, 129.74, 131.51, 140.48, 145.9, 151.78, 152.22, 155.91. Analysis results for C19H13N5: C, 73.30; H, 4.21; N, 22.49; found: C, 73.22; H, 4.31; N, 22.42; EIMS (m/z): 311.17 [M+].

A8 7-(2-Nitrophenyl)-2-(phenylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (7b)

Yellow crystals; mp: 268–270°C; yield: 0.320 g (90%); 1H NMR (600 MHz, DMSO-d 6) δ 6.90–6.93 (1H, m, Ar–H), 7.17–7.20 (2H, m, Ar–H), 7.39–7.41 (2H, m, Ar–H); 7.46 (1H, J = 4.8 Hz, Ar–H), 7.84–7.86 (1H, m, Ar–H), 7.94–7.97 (2H, m, Ar–H), 8.03–8.05 (1H, m, Ar–H), 8.39, 8.41 (1H, dd, J = 1.2, 1.2 Hz, C5–H), 8.79 (1H, J = 4.8 Hz, C6–H), 9.56 (1H, s, Ar–H), 13C NMR (150 MHz, DMSO-d 6) δ 68.12, 109.70, 113.06, 117.91, 117.99, 121.66, 124.63, 124.81, 128.49, 132.71, 134.98, 140.03, 144.57, 147.51, 150.51, 152.92, 156.09. Analysis performed for C19H12N6O2: C, 64.04; H, 3.39; N, 23.58; found: C, 64.12; H, 4.01; N, 23.67; EIMS (m/z) 356.02 [M+].

A9 7-(4-Methylphenyl)-2-(phenylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (7c)

Reddish brown crystals; mp: 270–272°C; yield: 0.289 g (89%); (toluene/acetone 10:6), 1H NMR (400 MHz, DMSO-d 6) δ 2.38 (3H, s, CH3), 6.94–7.69 (9H, m, Ar–H), 8.10 (1H, d, J = 1.2 Hz, C5–H), 8.66 (1H, d, J = 4.8 Hz, C6–H), 9.59 (1H, s, NH). Analysis performed for C20H15N5: C, 73.83; H, 4.65; N, 21.52; found: C, 73.88; H, 4.62; N, 2155.

A10 7-(4-Methoxyphenyl)-2-(phenylamino)pyrazolo [1,5-a]pyrimidine-3-carbonitrile (7d)

Orange crystals; mp: 168–170°C; yield: 0.307 g (88%); (toluene/acetone 10:6); 1H NMR (400 MHz, DMSO-d 6) δ 3.34 (3H, s, OCH3), 6.92–7.57 (9H, m, Ar–H), 8.13 (1H, d, J = 1.2 Hz, C5–H), 8.65 (1H, d, J = 4.8 Hz, C6–H), 9.85 (1H, s, NH). Analysis results for C20H15N5O: C, 70.37; H, 4.43; N, 20.52; found: C, 70.44; H, 4.42; N, 20.57.

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Received: 2021-08-13
Revised: 2021-11-22
Accepted: 2021-12-13
Published Online: 2022-01-28

© 2022 Moustafa Sherif Moustafa et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Artikel in diesem Heft

  1. Research Articles
  2. Kinetic study on the reaction between Incoloy 825 alloy and low-fluoride slag for electroslag remelting
  3. Black pepper (Piper nigrum) fruit-based gold nanoparticles (BP-AuNPs): Synthesis, characterization, biological activities, and catalytic applications – A green approach
  4. Protective role of foliar application of green-synthesized silver nanoparticles against wheat stripe rust disease caused by Puccinia striiformis
  5. Effects of nitrogen and phosphorus on Microcystis aeruginosa growth and microcystin production
  6. Efficient degradation of methyl orange and methylene blue in aqueous solution using a novel Fenton-like catalyst of CuCo-ZIFs
  7. Synthesis of biological base oils by a green process
  8. Efficient pilot-scale synthesis of the key cefonicid intermediate at room temperature
  9. Synthesis and characterization of noble metal/metal oxide nanoparticles and their potential antidiabetic effect on biochemical parameters and wound healing
  10. Regioselectivity in the reaction of 5-amino-3-anilino-1H-pyrazole-4-carbonitrile with cinnamonitriles and enaminones: Synthesis of functionally substituted pyrazolo[1,5-a]pyrimidine derivatives
  11. A numerical study on the in-nozzle cavitating flow and near-field atomization of cylindrical, V-type, and Y-type intersecting hole nozzles using the LES-VOF method
  12. Synthesis and characterization of Ce-doped TiO2 nanoparticles and their enhanced anticancer activity in Y79 retinoblastoma cancer cells
  13. Aspects of the physiochemical properties of SARS-CoV-2 to prevent S-protein receptor binding using Arabic gum
  14. Sonochemical synthesis of protein microcapsules loaded with traditional Chinese herb extracts
  15. MW-assisted hydrolysis of phosphinates in the presence of PTSA as the catalyst, and as a MW absorber
  16. Fabrication of silicotungstic acid immobilized on Ce-based MOF and embedded in Zr-based MOF matrix for green fatty acid esterification
  17. Superior photocatalytic degradation performance for gaseous toluene by 3D g-C3N4-reduced graphene oxide gels
  18. Catalytic performance of Na/Ca-based fluxes for coal char gasification
  19. Slow pyrolysis of waste navel orange peels with metal oxide catalysts to produce high-grade bio-oil
  20. Development and butyrylcholinesterase/monoamine oxidase inhibition potential of PVA-Berberis lycium nanofibers
  21. Influence of biosynthesized silver nanoparticles using red alga Corallina elongata on broiler chicks’ performance
  22. Green synthesis, characterization, cytotoxicity, and antimicrobial activity of iron oxide nanoparticles using Nigella sativa seed extract
  23. Vitamin supplements enhance Spirulina platensis biomass and phytochemical contents
  24. Malachite green dye removal using ceramsite-supported nanoscale zero-valent iron in a fixed-bed reactor
  25. Green synthesis of manganese-doped superparamagnetic iron oxide nanoparticles for the effective removal of Pb(ii) from aqueous solutions
  26. Desalination technology for energy-efficient and low-cost water production: A bibliometric analysis
  27. Biological fabrication of zinc oxide nanoparticles from Nepeta cataria potentially produces apoptosis through inhibition of proliferative markers in ovarian cancer
  28. Effect of stabilizers on Mn ZnSe quantum dots synthesized by using green method
  29. Calcium oxide addition and ultrasonic pretreatment-assisted hydrothermal carbonization of granatum for adsorption of lead
  30. Fe3O4@SiO2 nanoflakes synthesized using biogenic silica from Salacca zalacca leaf ash and the mechanistic insight into adsorption and photocatalytic wet peroxidation of dye
  31. Facile route of synthesis of silver nanoparticles templated bacterial cellulose, characterization, and its antibacterial application
  32. Synergistic in vitro anticancer actions of decorated selenium nanoparticles with fucoidan/Reishi extract against colorectal adenocarcinoma cells
  33. Preparation of the micro-size flake silver powders by using a micro-jet reactor
  34. Effect of direct coal liquefaction residue on the properties of fine blue-coke-based activated coke
  35. Integration of microwave co-torrefaction with helical lift for pellet fuel production
  36. Cytotoxicity of green-synthesized silver nanoparticles by Adansonia digitata fruit extract against HTC116 and SW480 human colon cancer cell lines
  37. Optimization of biochar preparation process and carbon sequestration effect of pruned wolfberry branches
  38. Anticancer potential of biogenic silver nanoparticles using the stem extract of Commiphora gileadensis against human colon cancer cells
  39. Fabrication and characterization of lysine hydrochloride Cu(ii) complexes and their potential for bombing bacterial resistance
  40. First report of biocellulose production by an indigenous yeast, Pichia kudriavzevii USM-YBP2
  41. Biosynthesis and characterization of silver nanoparticles prepared using seeds of Sisymbrium irio and evaluation of their antifungal and cytotoxic activities
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  45. Anti-colon cancer activities of green-synthesized Moringa oleifera–AgNPs against human colon cancer cells
  46. Phosphorus removal from aqueous solution by adsorption using wetland-based biochar: Batch experiment
  47. A low-cost and eco-friendly fabrication of an MCDI-utilized PVA/SSA/GA cation exchange membrane
  48. Synthesis, microstructure, and phase transition characteristics of Gd/Nd-doped nano VO2 powders
  49. Biomediated synthesis of ZnO quantum dots decorated attapulgite nanocomposites for improved antibacterial properties
  50. Preparation of metal–organic frameworks by microwave-assisted ball milling for the removal of CR from wastewater
  51. A green approach in the biological base oil process
  52. A cost-effective and eco-friendly biosorption technology for complete removal of nickel ions from an aqueous solution: Optimization of process variables
  53. Protective role of Spirulina platensis liquid extract against salinity stress effects on Triticum aestivum L.
  54. Comprehensive physical and chemical characterization highlights the uniqueness of enzymatic gelatin in terms of surface properties
  55. Effectiveness of different accelerated green synthesis methods in zinc oxide nanoparticles using red pepper extract: Synthesis and characterization
  56. Blueprinting morpho-anatomical episodes via green silver nanoparticles foliation
  57. A numerical study on the effects of bowl and nozzle geometry on performances of an engine fueled with diesel or bio-diesel fuels
  58. Liquid-phase hydrogenation of carbon tetrachloride catalyzed by three-dimensional graphene-supported palladium catalyst
  59. The catalytic performance of acid-modified Hβ molecular sieves for environmentally friendly acylation of 2-methylnaphthalene
  60. A study of the precipitation of cerium oxide synthesized from rare earth sources used as the catalyst for biodiesel production
  61. Larvicidal potential of Cipadessa baccifera leaf extract-synthesized zinc nanoparticles against three major mosquito vectors
  62. Fabrication of green nanoinsecticides from agri-waste of corn silk and its larvicidal and antibiofilm properties
  63. Palladium-mediated base-free and solvent-free synthesis of aromatic azo compounds from anilines catalyzed by copper acetate
  64. Study on the functionalization of activated carbon and the effect of binder toward capacitive deionization application
  65. Co-chlorination of low-density polyethylene in paraffin: An intensified green process alternative to conventional solvent-based chlorination
  66. Antioxidant and photocatalytic properties of zinc oxide nanoparticles phyto-fabricated using the aqueous leaf extract of Sida acuta
  67. Recovery of cobalt from spent lithium-ion battery cathode materials by using choline chloride-based deep eutectic solvent
  68. Synthesis of insoluble sulfur and development of green technology based on Aspen Plus simulation
  69. Photodegradation of methyl orange under solar irradiation on Fe-doped ZnO nanoparticles synthesized using wild olive leaf extract
  70. A facile and universal method to purify silica from natural sand
  71. Green synthesis of silver nanoparticles using Atalantia monophylla: A potential eco-friendly agent for controlling blood-sucking vectors
  72. Endophytic bacterial strain, Brevibacillus brevis-mediated green synthesis of copper oxide nanoparticles, characterization, antifungal, in vitro cytotoxicity, and larvicidal activity
  73. Off-gas detection and treatment for green air-plasma process
  74. Ultrasonic-assisted food grade nanoemulsion preparation from clove bud essential oil and evaluation of its antioxidant and antibacterial activity
  75. Construction of mercury ion fluorescence system in water samples and art materials and fluorescence detection method for rhodamine B derivatives
  76. Hydroxyapatite/TPU/PLA nanocomposites: Morphological, dynamic-mechanical, and thermal study
  77. Potential of anaerobic co-digestion of acidic fruit processing waste and waste-activated sludge for biogas production
  78. Synthesis and characterization of ZnO–TiO2–chitosan–escin metallic nanocomposites: Evaluation of their antimicrobial and anticancer activities
  79. Nitrogen removal characteristics of wet–dry alternative constructed wetlands
  80. Structural properties and reactivity variations of wheat straw char catalysts in volatile reforming
  81. Microfluidic plasma: Novel process intensification strategy
  82. Antibacterial and photocatalytic activity of visible-light-induced synthesized gold nanoparticles by using Lantana camara flower extract
  83. Antimicrobial edible materials via nano-modifications for food safety applications
  84. Biosynthesis of nano-curcumin/nano-selenium composite and their potentialities as bactericides against fish-borne pathogens
  85. Exploring the effect of silver nanoparticles on gene expression in colon cancer cell line HCT116
  86. Chemical synthesis, characterization, and dose optimization of chitosan-based nanoparticles of clodinofop propargyl and fenoxaprop-p-ethyl for management of Phalaris minor (little seed canary grass): First report
  87. Double [3 + 2] cycloadditions for diastereoselective synthesis of spirooxindole pyrrolizidines
  88. Green synthesis of silver nanoparticles and their antibacterial activities
  89. Review Articles
  90. A comprehensive review on green synthesis of titanium dioxide nanoparticles and their diverse biomedical applications
  91. Applications of polyaniline-impregnated silica gel-based nanocomposites in wastewater treatment as an efficient adsorbent of some important organic dyes
  92. Green synthesis of nano-propolis and nanoparticles (Se and Ag) from ethanolic extract of propolis, their biochemical characterization: A review
  93. Advances in novel activation methods to perform green organic synthesis using recyclable heteropolyacid catalysis
  94. Limitations of nanomaterials insights in green chemistry sustainable route: Review on novel applications
  95. Special Issue: Use of magnetic resonance in profiling bioactive metabolites and its applications (Guest Editors: Plalanoivel Velmurugan et al.)
  96. Stomach-affecting intestinal parasites as a precursor model of Pheretima posthuma treated with anthelmintic drug from Dodonaea viscosa Linn.
  97. Anti-asthmatic activity of Saudi herbal composites from plants Bacopa monnieri and Euphorbia hirta on Guinea pigs
  98. Embedding green synthesized zinc oxide nanoparticles in cotton fabrics and assessment of their antibacterial wound healing and cytotoxic properties: An eco-friendly approach
  99. Synthetic pathway of 2-fluoro-N,N-diphenylbenzamide with opto-electrical properties: NMR, FT-IR, UV-Vis spectroscopic, and DFT computational studies of the first-order nonlinear optical organic single crystal
https://doi.org/10.1515/gps-2022-0009
Schlagwörter für diesen Artikel
multicomponent reaction; regioselectivity; 7-aminopyrazolo[1,5-a]pyrimidines; microwave heating; X-ray crystallography
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Research Articles
  2. Kinetic study on the reaction between Incoloy 825 alloy and low-fluoride slag for electroslag remelting
  3. Black pepper (Piper nigrum) fruit-based gold nanoparticles (BP-AuNPs): Synthesis, characterization, biological activities, and catalytic applications – A green approach
  4. Protective role of foliar application of green-synthesized silver nanoparticles against wheat stripe rust disease caused by Puccinia striiformis
  5. Effects of nitrogen and phosphorus on Microcystis aeruginosa growth and microcystin production
  6. Efficient degradation of methyl orange and methylene blue in aqueous solution using a novel Fenton-like catalyst of CuCo-ZIFs
  7. Synthesis of biological base oils by a green process
  8. Efficient pilot-scale synthesis of the key cefonicid intermediate at room temperature
  9. Synthesis and characterization of noble metal/metal oxide nanoparticles and their potential antidiabetic effect on biochemical parameters and wound healing
  10. Regioselectivity in the reaction of 5-amino-3-anilino-1H-pyrazole-4-carbonitrile with cinnamonitriles and enaminones: Synthesis of functionally substituted pyrazolo[1,5-a]pyrimidine derivatives
  11. A numerical study on the in-nozzle cavitating flow and near-field atomization of cylindrical, V-type, and Y-type intersecting hole nozzles using the LES-VOF method
  12. Synthesis and characterization of Ce-doped TiO2 nanoparticles and their enhanced anticancer activity in Y79 retinoblastoma cancer cells
  13. Aspects of the physiochemical properties of SARS-CoV-2 to prevent S-protein receptor binding using Arabic gum
  14. Sonochemical synthesis of protein microcapsules loaded with traditional Chinese herb extracts
  15. MW-assisted hydrolysis of phosphinates in the presence of PTSA as the catalyst, and as a MW absorber
  16. Fabrication of silicotungstic acid immobilized on Ce-based MOF and embedded in Zr-based MOF matrix for green fatty acid esterification
  17. Superior photocatalytic degradation performance for gaseous toluene by 3D g-C3N4-reduced graphene oxide gels
  18. Catalytic performance of Na/Ca-based fluxes for coal char gasification
  19. Slow pyrolysis of waste navel orange peels with metal oxide catalysts to produce high-grade bio-oil
  20. Development and butyrylcholinesterase/monoamine oxidase inhibition potential of PVA-Berberis lycium nanofibers
  21. Influence of biosynthesized silver nanoparticles using red alga Corallina elongata on broiler chicks’ performance
  22. Green synthesis, characterization, cytotoxicity, and antimicrobial activity of iron oxide nanoparticles using Nigella sativa seed extract
  23. Vitamin supplements enhance Spirulina platensis biomass and phytochemical contents
  24. Malachite green dye removal using ceramsite-supported nanoscale zero-valent iron in a fixed-bed reactor
  25. Green synthesis of manganese-doped superparamagnetic iron oxide nanoparticles for the effective removal of Pb(ii) from aqueous solutions
  26. Desalination technology for energy-efficient and low-cost water production: A bibliometric analysis
  27. Biological fabrication of zinc oxide nanoparticles from Nepeta cataria potentially produces apoptosis through inhibition of proliferative markers in ovarian cancer
  28. Effect of stabilizers on Mn ZnSe quantum dots synthesized by using green method
  29. Calcium oxide addition and ultrasonic pretreatment-assisted hydrothermal carbonization of granatum for adsorption of lead
  30. Fe3O4@SiO2 nanoflakes synthesized using biogenic silica from Salacca zalacca leaf ash and the mechanistic insight into adsorption and photocatalytic wet peroxidation of dye
  31. Facile route of synthesis of silver nanoparticles templated bacterial cellulose, characterization, and its antibacterial application
  32. Synergistic in vitro anticancer actions of decorated selenium nanoparticles with fucoidan/Reishi extract against colorectal adenocarcinoma cells
  33. Preparation of the micro-size flake silver powders by using a micro-jet reactor
  34. Effect of direct coal liquefaction residue on the properties of fine blue-coke-based activated coke
  35. Integration of microwave co-torrefaction with helical lift for pellet fuel production
  36. Cytotoxicity of green-synthesized silver nanoparticles by Adansonia digitata fruit extract against HTC116 and SW480 human colon cancer cell lines
  37. Optimization of biochar preparation process and carbon sequestration effect of pruned wolfberry branches
  38. Anticancer potential of biogenic silver nanoparticles using the stem extract of Commiphora gileadensis against human colon cancer cells
  39. Fabrication and characterization of lysine hydrochloride Cu(ii) complexes and their potential for bombing bacterial resistance
  40. First report of biocellulose production by an indigenous yeast, Pichia kudriavzevii USM-YBP2
  41. Biosynthesis and characterization of silver nanoparticles prepared using seeds of Sisymbrium irio and evaluation of their antifungal and cytotoxic activities
  42. Synthesis, characterization, and photocatalysis of a rare-earth cerium/silver/zinc oxide inorganic nanocomposite
  43. Developing a plastic cycle toward circular economy practice
  44. Fabrication of CsPb1−xMnxBr3−2xCl2x (x = 0–0.5) quantum dots for near UV photodetector application
  45. Anti-colon cancer activities of green-synthesized Moringa oleifera–AgNPs against human colon cancer cells
  46. Phosphorus removal from aqueous solution by adsorption using wetland-based biochar: Batch experiment
  47. A low-cost and eco-friendly fabrication of an MCDI-utilized PVA/SSA/GA cation exchange membrane
  48. Synthesis, microstructure, and phase transition characteristics of Gd/Nd-doped nano VO2 powders
  49. Biomediated synthesis of ZnO quantum dots decorated attapulgite nanocomposites for improved antibacterial properties
  50. Preparation of metal–organic frameworks by microwave-assisted ball milling for the removal of CR from wastewater
  51. A green approach in the biological base oil process
  52. A cost-effective and eco-friendly biosorption technology for complete removal of nickel ions from an aqueous solution: Optimization of process variables
  53. Protective role of Spirulina platensis liquid extract against salinity stress effects on Triticum aestivum L.
  54. Comprehensive physical and chemical characterization highlights the uniqueness of enzymatic gelatin in terms of surface properties
  55. Effectiveness of different accelerated green synthesis methods in zinc oxide nanoparticles using red pepper extract: Synthesis and characterization
  56. Blueprinting morpho-anatomical episodes via green silver nanoparticles foliation
  57. A numerical study on the effects of bowl and nozzle geometry on performances of an engine fueled with diesel or bio-diesel fuels
  58. Liquid-phase hydrogenation of carbon tetrachloride catalyzed by three-dimensional graphene-supported palladium catalyst
  59. The catalytic performance of acid-modified Hβ molecular sieves for environmentally friendly acylation of 2-methylnaphthalene
  60. A study of the precipitation of cerium oxide synthesized from rare earth sources used as the catalyst for biodiesel production
  61. Larvicidal potential of Cipadessa baccifera leaf extract-synthesized zinc nanoparticles against three major mosquito vectors
  62. Fabrication of green nanoinsecticides from agri-waste of corn silk and its larvicidal and antibiofilm properties
  63. Palladium-mediated base-free and solvent-free synthesis of aromatic azo compounds from anilines catalyzed by copper acetate
  64. Study on the functionalization of activated carbon and the effect of binder toward capacitive deionization application
  65. Co-chlorination of low-density polyethylene in paraffin: An intensified green process alternative to conventional solvent-based chlorination
  66. Antioxidant and photocatalytic properties of zinc oxide nanoparticles phyto-fabricated using the aqueous leaf extract of Sida acuta
  67. Recovery of cobalt from spent lithium-ion battery cathode materials by using choline chloride-based deep eutectic solvent
  68. Synthesis of insoluble sulfur and development of green technology based on Aspen Plus simulation
  69. Photodegradation of methyl orange under solar irradiation on Fe-doped ZnO nanoparticles synthesized using wild olive leaf extract
  70. A facile and universal method to purify silica from natural sand
  71. Green synthesis of silver nanoparticles using Atalantia monophylla: A potential eco-friendly agent for controlling blood-sucking vectors
  72. Endophytic bacterial strain, Brevibacillus brevis-mediated green synthesis of copper oxide nanoparticles, characterization, antifungal, in vitro cytotoxicity, and larvicidal activity
  73. Off-gas detection and treatment for green air-plasma process
  74. Ultrasonic-assisted food grade nanoemulsion preparation from clove bud essential oil and evaluation of its antioxidant and antibacterial activity
  75. Construction of mercury ion fluorescence system in water samples and art materials and fluorescence detection method for rhodamine B derivatives
  76. Hydroxyapatite/TPU/PLA nanocomposites: Morphological, dynamic-mechanical, and thermal study
  77. Potential of anaerobic co-digestion of acidic fruit processing waste and waste-activated sludge for biogas production
  78. Synthesis and characterization of ZnO–TiO2–chitosan–escin metallic nanocomposites: Evaluation of their antimicrobial and anticancer activities
  79. Nitrogen removal characteristics of wet–dry alternative constructed wetlands
  80. Structural properties and reactivity variations of wheat straw char catalysts in volatile reforming
  81. Microfluidic plasma: Novel process intensification strategy
  82. Antibacterial and photocatalytic activity of visible-light-induced synthesized gold nanoparticles by using Lantana camara flower extract
  83. Antimicrobial edible materials via nano-modifications for food safety applications
  84. Biosynthesis of nano-curcumin/nano-selenium composite and their potentialities as bactericides against fish-borne pathogens
  85. Exploring the effect of silver nanoparticles on gene expression in colon cancer cell line HCT116
  86. Chemical synthesis, characterization, and dose optimization of chitosan-based nanoparticles of clodinofop propargyl and fenoxaprop-p-ethyl for management of Phalaris minor (little seed canary grass): First report
  87. Double [3 + 2] cycloadditions for diastereoselective synthesis of spirooxindole pyrrolizidines
  88. Green synthesis of silver nanoparticles and their antibacterial activities
  89. Review Articles
  90. A comprehensive review on green synthesis of titanium dioxide nanoparticles and their diverse biomedical applications
  91. Applications of polyaniline-impregnated silica gel-based nanocomposites in wastewater treatment as an efficient adsorbent of some important organic dyes
  92. Green synthesis of nano-propolis and nanoparticles (Se and Ag) from ethanolic extract of propolis, their biochemical characterization: A review
  93. Advances in novel activation methods to perform green organic synthesis using recyclable heteropolyacid catalysis
  94. Limitations of nanomaterials insights in green chemistry sustainable route: Review on novel applications
  95. Special Issue: Use of magnetic resonance in profiling bioactive metabolites and its applications (Guest Editors: Plalanoivel Velmurugan et al.)
  96. Stomach-affecting intestinal parasites as a precursor model of Pheretima posthuma treated with anthelmintic drug from Dodonaea viscosa Linn.
  97. Anti-asthmatic activity of Saudi herbal composites from plants Bacopa monnieri and Euphorbia hirta on Guinea pigs
  98. Embedding green synthesized zinc oxide nanoparticles in cotton fabrics and assessment of their antibacterial wound healing and cytotoxic properties: An eco-friendly approach
  99. Synthetic pathway of 2-fluoro-N,N-diphenylbenzamide with opto-electrical properties: NMR, FT-IR, UV-Vis spectroscopic, and DFT computational studies of the first-order nonlinear optical organic single crystal
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