Introduction

The booming field of diversity-oriented synthesis (DOS) has been exploited to generate novel and highly functionalized small molecule libraries. The development of environmentally sound, green and economic synthetic procedures is of utmost interest. Among key criteria for green chemistry, the design of energy-efficient processes and the use of safer solvents are highly sought [1, 2].

Microwave-assisted organic synthesis (MAOS) enables chemists save time and prepare products in almost quantitative yields and with high selectivity. Thus, this technology is now being used widely as an alternative to conventional heating in many reaction types [3, 4]. MAOS in combination with multicomponent synthesis aligns with the principles of green chemistry that include atom economy, facile execution, ease of diversification and high reaction efficiency [5, 6].

Organic synthesis in aqueous media is of high interest due to the unique properties of water such as immense heat capacity, high dielectric constant, large temperature window, low cost and eco-compatibility [7,8,9]. In this regard, the development of green protocols in water under microwave irradiation is highly desirable.

As bioactive molecular frameworks, pyrazoles can serve as lead compounds for the development of new pharmaceuticals [10]. In particular, 4,5-dihydro-1H-pyrazole-1-carbothioamides (DPCs) are established as potent therapeutics for several CNS diseases such as Parkinson’s and Alzheimer’s by selective inhibition against both isoforms of monoamine oxidase (MAO) (Fig. 1) [11]. Furthermore, this privileged scaffold stands out as an effective antidepressant [12].

In addition, this type of compounds has been described with superior anticancer activity against the MCF-7 (human breast) [13], HeLa (human cervix) [14], 5647 and T24 (human bladder) [15] carcinoma cell lines. Other biological evaluations revealed that 4,5-dihydro-1H-pyrazole-1-carbothioamide derivatives demonstrate promising antimicrobial [16], antiviral [17], anti-inflammatory [18], antitubercular [19] and anti-amebic [20] behaviors. Encouraged by these pharmacological and biological properties, we envisaged to develop a green procedure for the synthesis of thiocarbamoyl pyrazolines. A well-established strategy the synthesis of DPCs usually adopts the condensation of chalcones with thiosemicarbazide in the presence of sodium or potassium hydroxide [21]. Another route involves the reaction of 3,5-diaryl-4,5-dihydro-1H-pyrazoles and isothiocyanate derivatives [22]. In contrast to the many multistep processes reported for the syntheses of DPCs, these methodologies pose a series of challenges such as low yields (48–58%), limited substrate scopes, long reaction times and use of organic solvents [23,24,25,26]. Furthermore, some procedures require the separation and purification of chalcone as a key precursor [27,28,29,30].

To overcome these limitations, and considering the need to develop convenient, versatile, sustainable and rapid strategies to expeditiously prepare these biologically active molecules for newer therapeutic applications, we put forward a new and facile synthesis of DPCs through the multicomponent reaction of aryl aldehydes, acetophenones and thiosemicarbazide utilizing tetrabutylammonium hydroxide (TBAOH, 40 wt.% in water) under microwave irradiation (Scheme 1).

Fig. 1
figure 1

Example of a DPC with MAO-B inhibitory activity

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Scheme 1
scheme 1

Multicomponent synthesis of DPCs

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This protocol is superior to the reported methods based on simplicity, efficiency, yield, reaction time and expansion of substrate scope. Moreover, to our knowledge, there is no report on the synthesis of DPCs using a multicomponent reaction involving aryl aldehydes and acetophenones as substrates. In addition, the present methodology has some of the important features of green chemistry, such as avoiding the use of hazardous organic solvents, harsh reaction conditions and sophisticated catalysts in conjugation with the elimination of unnecessary reaction steps.

Results and discussion

We initially explored the reaction conditions by conducting the three-component reaction using 4-chloro-benzaldehyde, 4-chloroacetophenone and thiosemicarbazide (Table 1). With the purpose of screening catalytic efficiency, different basic catalysts such as NaOH, KOH, \(\hbox {Et}_{3}\hbox {N}\) and DABCO were used in this reaction. The results indicated that utilizing TBAOH increased the yield dramatically (Table 1, entries 1–5). Meanwhile, a control experiment verified that the presence of a catalyst is indispensable for this reaction as no target heterocycle was obtained in the absence of catalysts (Table 1, entry 6). Among all tested systems, 1 mL of TBAOH was the best amount (Table 1, entries 5, 7 and 8). In terms of chemical yields, 70 \({^{\circ }}\hbox {C}\) was found as the ideal temperature for this transformation (Table 1, entries 5 and 9–11).

Table 1 Optimization parameters for formation of DPC
figure a
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Afterward, the influence of different microwave irradiation output power on the model reaction was appraised (Table 1, entries 5, 12 and 13). It was found that maximum yield reached a plateau at 300 W. To evaluate the superiority of our MW irradiation procedure over a conventional heating system, compound 3c was synthesized by heating conventionally the reaction to 70 \({^{\circ }}\hbox {C}\) and the product was obtained in much lower yield (< 40%, Table 1, entry 14) requiring a much longer reaction time compared with MW-assisted synthesis (95%, Table 1, entry 5). Moreover, under ultrasonic irradiation (at 70 \({^{\circ }}\hbox {C}\)), the corresponding product was obtained only in 64% yield (Table 1, entry 15). This procedure eliminates the need for chalcone work-up and purification, and it vastly improved reaction yield. For example, isolation of chalcone prepared by the reaction of 4-chlorobenzaldehyde and acetophenone and further condensation with thiosemicarbazide produced the corresponding DPC in only 47% yield, whereas our new multicomponent procedure dramatically doubled the yield (Table 1, entry 3).

Table 2 Synthesis of 4,5-dihydro-1H-pyrazole-1-carbothioamides in the presence of TBAOH under microwave irradiation
figure b
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Using our optimized reaction conditions, we synthesized a series of DPCs in the presence of TBAOH under microwave irradiation. As shown in Table 2, these compounds were synthesized in high to excellent yields using various aromatic aldehydes and acetophenones regardless of the electronic effect of the substituents on the aromatic rings. The stereoselectivity of this reaction has not been addressed because the products are formed as racemic mixtures. Surprising results were obtained when this new protocol was compared with the last modified methods that have been published (Table 2). For example, in the previous methods synthesis of 3j required more than 8 h to be obtained in only 40% yield [17]; however, with the present method 3j was attained in 93% after only 90 s (Table 2, entry 10).

From practical and industrial points of view, the recyclability of the catalyst is highly desirable. Due to superior solubility of TBAOH in water, it could be readily recovered by washing with distilled water and successive evaporation at \(80\, {^{\circ }}\hbox {C}\). The results revealed that the initial volume of the catalyst and its activity could be retained after five consecutive runs.

To investigate the efficiency and practical application of the developed protocol for synthesis of DPCs, the optimized process for preparation of 3c was extended to a 10.0 mmol scale retaining the reaction stoichiometry intact. Gratifyingly, a comparable yield (91%) for 3c was obtained.

Conclusion

In summary, a straightforward multicomponent procedure for synthesis of DPCs using aryl aldehydes, acetophenones and thiosemicarbazide with catalytic TBAOH under microwave irradiation has been reported. This methodology provides access to DPCs with structural and functional diversities while featuring improved sustainability, high yields, experimental simplicity and reusability of the catalyst. Furthermore, the process is suitable to apply in large-scale preparation of 4,5-dihydro-1H-pyrazole-1-carbothioamide derivatives in convenient manner.

Experimental

General

All chemicals used were purchased from Fluka and Merck chemical companies and used without further purification. For thin-layer chromatography (TLC), 0.25-mm precoated silica \(\hbox {HF}_{254}\) plates were used. \(^{1}\hbox {H}\) and \(^{13}\hbox {C}\) NMR spectra were recorded on Brüker Avance 400 and 500 MHz Fourier-transform spectrometers in \(\hbox {CDCl}_{3}\). Coupling constants are reported in Hertz (NMR abbreviations: s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, m = multiplet, J = coupling constant). FT-IR spectra were recorded on a Nicolet-Impact 400D instrument (range 400–4000 \(\hbox { cm}^{-1})\). Melting point determination was done using Stuart Scientific SMP2 apparatus and was not corrected. Mass analysis was carried out with a Platform II spectrometer from Micromass; EI mode at 70 eV. Elemental analysis was conducted on a LECO, CHNS-932 analyzer. The microwave system used in these experiments includes the following items: Micro-SYNTH labstation equipped with a glass door, a dual magnetron system with pyramid-shaped diffuser, 1000 W delivered power, exhaust system, magnetic stirrer, “quality pressure” sensor for flammable organic solvents and a ATCFO fiber optic system for automatic temperature control.

General procedure

An aldehyde (1 mmol), acetophenone (1 mmol), thiosemicarbazide (2 mmol) and TBAOH (1 mL, 40 wt.% in water) were added to a Teflon microwave reaction vessel equipped with a magnetic stirrer bar. The reaction mixture was subjected to microwave irradiation (300 W, 70 \({^{\circ }}\hbox {C}\)) for 60 s. After completion of the reaction (monitored by TLC), the reaction mixture was allowed to cool down to room temperature, filtered and washed with cold water to give crude product, which was purified by recrystallization from ethanol.

Selected spectral data

5-(Anthracen-10-yl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide (3k)

White solid, \(\hbox {mp} = 215\)–216 \({^{\circ }}\hbox {C}, \hbox {IR (KBr)}: \upsilon = 3432\)–3221 \((\hbox {N--H}), 1579 (\hbox {C}{=}\hbox {N}), 1502\)–1440 \((\hbox {C}{=}\hbox {C}), 1364 (\hbox {C}{=}\hbox {S}) \hbox { cm}^{-1}\). \({}^{1}\hbox {H}\hbox { NMR}\; (500\hbox { MHz}, \hbox {CDCl}_{3}): \delta = 3.17\;(\hbox {dd}, J_{\mathrm{ab} }= 17.8\hbox { Hz}, J_{\mathrm{ac}} = 3.6\hbox { Hz}, \hbox {1H}, \hbox {H}_{\mathrm{a}})\), \(3.88\; (\hbox {dd}, J_{\mathrm{ab} }= 17.8\hbox { Hz}, J_{\mathrm{bc}} = 11.6\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{b}}), 7.06\; (\hbox {dd}, J_{\mathrm{ac}} = 3.6\hbox { Hz}, J_{\mathrm{bc}} = 11.6\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{c}}), 7.13\)–\(8.37 (\hbox {m}, 14\hbox {H}, \hbox {Ar})\), 6.95 and 7.05 (s, 2H, \(\hbox {NH}_{2}\)); \({}^{13}\hbox {C}\) NMR (400 MHz, \(\hbox {CDCl}_{3}\)): \(\delta = 43.0\) (C4), 62.8 (C5), 126.9, 127.0, 127.6, 127.9, 128.2, 128.9, 129.1, 129.8, 130.4, 130.9, 131.2, 132.0, 133.4, 136.0, 139.4, 130.4 (20C, Ar), 155.9 (C3), 176.7 (C(S)\(\hbox {NH}_{2}\)). MS (EI): m/z (%) 381 (M\(^{+}\), 21.01), 306 (9.66), 202 (100.00), 178 (89.69), 76 (74.74), 59 (77.32).

5-(4-Bromophenyl)-3-(4-chlorophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (3o)

White solid, \(\hbox {mp} = 210\)–211 \({^{\circ }}\hbox {C}\), IR (KBr): \(\upsilon =3481\)–3356 (N–H), 1568 \((\hbox {C}{=}\hbox {N})\), 1501–1443 \((\hbox {C}{=}\hbox {C})\), 1353 \((\hbox {C}{=}\hbox {S})\) \(\hbox { cm}^{-1}\). \({}^{1}\hbox {H}\) NMR (400 MHz, \(\hbox {CDCl}_{3}\)): \(\delta = 3.1\; (\hbox {dd}, J_{\mathrm{ab}}= 17.6\hbox { Hz}, J_{\mathrm{ac}}= 3.4\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{a}})\), 3.54 (dd, \(J_{\mathrm{ab}}= 17.6\hbox { Hz}, J_{\mathrm{bc}}= 11.6\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{b}}\)), 5.68 (dd, \(J_{\mathrm{ac}}= 3.4\hbox { Hz}, J_{\mathrm{bc}}= 11.6\hbox { Hz}\), 1H, \(\hbox {H}_{\mathrm{c}}\)), 7.02–7.65 (m, 8H, Ar), 6.07 and 7.02 (s, 2H, NH\(_{2}\)). \(^{13}\hbox {C}\) NMR (400 MHz, \(\hbox {CDCl}_{3})\): \(\delta = 42.9\; (\hbox {C}_{4}), 62.9 (\hbox {C}_{5})\), 121.5, 126.9, 127.3, 128.9, 120.4, 131.2, 132.0, 140.8 (12C, Ar), 155.9 \((\hbox {C}_{3})\), 176.8 (C(S)\(\hbox {NH}_{2}\)). MS (EI): m/z (%) 393 (M\(^{+}\), 5.35), 254.9 (2.45), 178 (13.40), 101 (34.17), 74.85 (45.56), 59.84 (100.00).

5-(3-Bromophenyl)-3-(4-chlorophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (3p)

White solid, \(\hbox {mp }= 208\)–209 \({^{\circ }}\hbox {C}\), IR (KBr): \(\upsilon =3480\)–\(3345\; (\hbox {N--H}), 1571 \;(\hbox {C}{=}\hbox {N})\), 1501–1445 \((\hbox {C}{=}\hbox {C}), 1363\; (\hbox {C}{=}\hbox {S}) \hbox { cm}^{-1}\). \(^{1}\hbox {H}\hbox { NMR}\; (500\hbox { MHz}, \hbox {CDCl}_{3}): \delta = 3.21\; (\hbox {dd}, J_{\mathrm{ab}}= 17.8\hbox { Hz}, J_{\mathrm{ac}}= 3.6\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{a}}), 3.88 (\hbox {dd}, J_{\mathrm{ab}}= 17.8\hbox { Hz}, J_{\mathrm{bc}}= 11.6\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{b}}), 6.03\; (\hbox {dd}, J_{\mathrm{ac}}= 3.6\hbox { Hz}, J_{\mathrm{bc}}= 11.6\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{c}})\), 7.05–7.43 (m, 8H, Ar), 6.04 and 7.19 (s, 2H, NH\(_{2}\)). \({}^{13}\hbox {C}\) NMR (400 MHz, \(\hbox {CDCl}_{3}): \delta = 42.8\; (\hbox {C}_{4}), 63.0\; (\hbox {C}_{5})\), 124.5, 127.0, 127.4, 128.9, 130.5, 131.2, 132.0, 140.8, 142.8, 144.7 (12C, Ar), 155.9 \((\hbox {C}_{3})\), 176.8 (C(S)\(\hbox {NH}_{2}\)). MS (EI): m/z (%) 393 (M\(^{+}\), 1.07), 254 (2.07), 179 (10.58), 102 (44.81), 75 (81.74), 55 (100.00).

5-(2-Bromophenyl)-3-(4-chlorophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (\({{\varvec{3q}}}\))

White solid, \(\hbox {mp} = 209\)–210 \({^{\circ }}\hbox {C}\), IR (KBr): \(\upsilon =3475\)–3286 \(\hbox {(N--H)}, 1567\; (\hbox {C}{=}\hbox {N}), 1503\)–\(1442\; (\hbox {C}{=}\hbox {C}), 1350 \;(\hbox {C}{=}\hbox {S}) \hbox { cm}^{-1}\). \({}^{1}\hbox {H}\hbox { NMR }(500\hbox { MHz}, \hbox {CDCl}_{3}): \delta = 3.21 \;(\hbox {dd}, J_{\mathrm{ab}}= 17.8\hbox { Hz}, J_{\mathrm{ac}}= 3.6\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{a}})\), \(3.87 \;(\hbox {dd}, J_{\mathrm{ab}}= 17.8\hbox { Hz}, J_{\mathrm{bc}}= 11.6\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{b}}), 6.03 \;(\hbox {dd}, J_{\mathrm{ac}}= 3.6\hbox { Hz}, J_{\mathrm{bc}}= 11.6\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{c}})\), 7.19–7.67 (m, 8H, Ar), 6.04 and 7.20 (s, 2H, NH\(_{2}\)). \({}^{13}\hbox {C}\) NMR (400 MHz, \(\hbox {CDCl}_{3}): \delta = 43.0 (\hbox {C}_{4}), 62.9 (\hbox {C}_{5})\), 122.5, 126.9, 127.0, 128.9, 129.2, 130.6, 131.1, 133.4, 140.4, 142.6 (12C, Ar), 155.8 \((\hbox {C}_{3})\), 176.6 (C(S)\(\hbox {NH}_{2}\)). MS (EI): m/z (%) 393 (\(\hbox {M}^{+}\), 1.16), 314 (52.67), 179 (10.83), 101 (35.67), 74 (55.33), 59 (100.00).

5-(2,4-Dichlorophenyl)-3-p-tolyl-4,5-dihydro-1H-pyrazole-1-carbothioamide (\({{\varvec{3e}}'}\))

White solid, \(\hbox {mp }= 203\)–204 \({^{\circ }}\hbox {C}\), IR (KBr): \(\upsilon = 3428\)–\(3264~\hbox {(N--H)}, 1591\;(\hbox {C}{=}\hbox {N}), 1501\)–\(1460\;(\hbox {C}{=}\hbox {C}), 1370\;(\hbox {C}{=}\hbox {S}) \hbox { cm}^{-1}\). \({}^{1}\hbox {H}\hbox { NMR } (500\hbox { MHz}, \hbox {CDCl}_{3})\): \(\delta = 2.43\; (\hbox {s}, \hbox {3H}, \hbox {CH}_{3}), 3.12\; (\hbox {dd}, J_{\mathrm{ab}}= 18.5\hbox { Hz}, J_{\mathrm{ac}}= 4 \hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{a}}), 3.94 (\hbox {dd}, J_{\mathrm{ab}}= 18.5\hbox { Hz}, J_{\mathrm{bc}}= 11.5\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{b}}), 6.31 (\hbox {dd}, J_{\mathrm{ac}}= 4\hbox { Hz}, J_{\mathrm{bc}}= 11.5\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{c}})\), 7.04–7.46 (m, 7H, Ar), 6.20 and 7.19 (s, 2H, NH\(_{2}\)). \({}^{13}\hbox {C}\hbox { NMR }(500\hbox { MHz}, \hbox {CDCl}_{3})\): \(\delta = 22.0\; (\hbox {CH}_{3}), 42.3 (\hbox {C}_{4})\), 61.3 \((\hbox {C}_{5})\), 123.5, 127.3, 127.9, 128.0, 130.0, 130.2, 132.4, 134.2, 137.8, 142.3 (12C, Ar), 155.1 \((\hbox {C}_{3})\), 176.8 (C(S)\(\hbox {NH}_{2}\)). MS (EI): m/z (%) 363(\(\hbox {M}^{+}\), 4.32), 327 (100.00), 158 (77.73), 90 (82.46), 76 (29.62), 59 (86.26).

5-(2-Chloro-6-fluorophenyl)-3-p-tolyl-4,5-dihydro-1H-pyrazole-1-carbothioamide (\({{\varvec{3f}}'}\))

White solid, \(\hbox {mp} = 218\)–\(220~{^{\circ }}\hbox {C},\hbox { IR (KBr)}: \upsilon = 3448\)–\(3242\; \hbox {(N--H)}, 1580\; (\hbox {C}{=}\hbox {N}), 1500\)–\(1430\; (\hbox {C}{=}\hbox {C}), 1377\; (\hbox {C}{=}\hbox {S}) \hbox { cm}^{-1}. {}^{1}\hbox {H}\hbox { NMR} (400\hbox { MHz}, \hbox {CDCl}_{3}): \delta =2.33\; (\hbox {s}, 3\hbox {H}, \hbox {CH}_{3}), 3.18\; (\hbox {dd}, J_{\mathrm{ab}}= 17.6\hbox { Hz}, J_{\mathrm{ac}}= 3.6\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{a}}), 3.81\; (\hbox {dd}, J_{\mathrm{ab}}= 17.6\hbox { Hz}, J_{\mathrm{bc}} = 11.2\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{b}}), 6.02 (\hbox {dd}, J_{\mathrm{ac}}= 3.6\hbox { Hz}, J_{\mathrm{bc}}= 11.2\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{c}})\), 6.86-7.69 (m, 7H, Ar), 6.19 and 7.08 (s, 2H, NH\(_{2}\)).\({}^{13}\hbox {C}\hbox { NMR }(400\hbox { MHz}, \hbox {CDCl}_{3})\): \(\delta = 22.2\; (\hbox {CH}_{3}), 43.18\; (\hbox {C}_{4}), 63.3\; (\hbox {C}_{5})\), 115.3, 127.5, 129.1, 129.2, 131.0, 132.6, 132.8, 136.2, 140.0, 163.6 (12C, Ar), 156.3 \((\hbox {C}_{3})\), 176.9 (C(S)\(\hbox {NH}_{2}\)). MS (EI): m/z (%) 347 (\(\hbox {M}^{+}\), 3.06), 286 (52.94), 158 (89.41), 90 (87.45), 76 (74.51), 59 (87.84).

5-(Naphthalene-1-yl)-3-p-tolyl-4,5-dihydro-1H-pyrazole-1-carbothioamide (\({\varvec{3k}}'\))

White solid, \(\hbox {mp} = 218\)–\(219~{^{\circ }}\hbox {C}\), IR (KBr): \(\upupsilon = 3422\)–3259 (N–H), 1591 \((\hbox {C}{=}\hbox {N})\), 1502–1442 \((\hbox {C}{=}\hbox {C}), 1368\; (\hbox {C}{=}\hbox {S}) \hbox { cm}^{-1}\). \({}^{1}\hbox {H}\hbox { NMR }(500\hbox { MHz}, \hbox {CDCl}_{3})\): \(\delta = 2.29 (\hbox {s}, \hbox {3H}, \hbox {CH}_{3})\), 3.07 (dd, \(J_{\mathrm{ab}}= 17.5\hbox { Hz}, J_{\mathrm{ac}}= 3.5\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{a}}), 3.94\; (\hbox {dd}, J_{\mathrm{ab}}= 17.5\hbox { Hz}, J_{\mathrm{bc}}= 11.5\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{b}}), 6.72\; (\hbox {dd}, J_{\mathrm{ac}}= 3.5 \hbox { Hz}, J_{\mathrm{bc}}= 11.5\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{c}})\), 7.1–7.8 (m, 11H, Ar), 6.20 and 7.19 (s, 2H, NH\(_{2}\)). \({}^{13}\hbox {C}\) NMR (400 MHz, \(\hbox {CDCl}_{3}\)): \(\delta = 21.6 (\hbox {CH}_{3}), 43.6\; (\hbox {C}_{4}), 63.6 (\hbox {C}_{5})\), 125.4, 126.9, 128.4, 128.9, 129.7, 130.7, 131.1, 133.4, 134.4, 135.6, 137.4, 138.9, 140.5, 143.8 (16C, Ar), 156.6 \((\hbox {C}_{3})\), 177.3 (C(S)\(\hbox {NH}_{2}\)). MS (EI): m/z (%) 345 (M\(^{+}\), 3.29), 270 (3.82), 158 (12.83), 90 (42.76), 76 (57.24), 54 (100.00).

5-(Anthracen-10-yl)-3-p-tolyl-4,5-dihydro-1H-pyrazole-1-carbothioamide (\({\varvec{3l}}'\))

White solid, \(\hbox {mp} = 222\)–\(223~{^{\circ }}\hbox {C}\), IR (KBr): \(\upsilon = 3433\)–3252 (N–H), 1586 \((\hbox {C}{=}\hbox {N})\), 1501–1441 \((\hbox {C}{=}\hbox {C}), 1367\; (\hbox {C}{=}\hbox {S}) \hbox { cm}^{-1}\). \(^{1}\hbox {H}\hbox { NMR}\; (500\hbox { MHz}, \hbox {CDCl}_{3})\): \(\delta =2.15 (\hbox {s}, 3\hbox {H}, \hbox {CH}_{3}), 3.22 (\hbox {dd}, J_{\mathrm{ab}}= 17.75\hbox { Hz}, J_{\mathrm{ac}}= 3.75\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{a}}), 3.8 (\hbox {dd}, J_{\mathrm{ab}}= 17.75\hbox { Hz}, J_{\mathrm{bc}} = 11.5\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{b}}), 7.05\; (\hbox {dd}, J_{\mathrm{ac}}= 3.75 \hbox { Hz}, J_{\mathrm{bc}}= 11.5\hbox { Hz}, 1\hbox {H}, \hbox {H}_{\mathrm{c}})\), 7.01–8.29 (m, 13H, Ar), 6.99 and 7.06 (s, 2H, NH2). \({}^{13}\hbox {C}\) NMR (400 MHz, \(\hbox {CDCl}_{3}\)): \(\delta = 21.6\; (\hbox {CH}_{3}), 43.3 (\hbox {C}_{4}), 63.2\; (\hbox {C}_{5})\), 125.4, 127.1, 128.1, 128.2, 128.9, 129.6, 130.7, 131.0, 132.1, 132.3, 133.2, 136.4, 137.3, 138.9, 139.9, 142.7 (20C, Ar), 156.3 \((\hbox {C}_{3})\), 176.9 (C(S)\(\hbox {NH}_{2}\)). MS (EI): m/z (%) 395 (\(\hbox {M}^{+}\), 91.76), 334 (39.01), 202 (100.00), 178 (100.00), 76 (17.58), 59 (42.31).