The preparation of N‐(1H‐pyrazol‐3‐yl)arylamides and 1H‐pyrazol‐3‐amines from polylithiated C(α),N‐thiosemicarbazones and C(α),N‐semicarbazones

Abstract

C(α),N‐Thiosemicarbazones or C(α),N‐semicarbazones were polylithiated with excess lithium diiso‐propylamide, and the resulting cyclized intermediates were condensed with aromatic esters to afford N‐(1H‐pyrazol‐3‐yl)arylamides. The polylithiated intermediates were also quenched with aqueous acid to give 5‐substituted, 1H‐pyrazol‐3‐amines.

Synthesis and Antimicrobial Activity of Novel Heterocycles Utilizing 3‐(1,4‐Dioxo‐3,4‐dihydrophthalazin‐2(1H)‐yl)‐3‐oxopropanenitrile as Precursors

“…The IR spectrum of 7b displayed the lack of nitrile and carbonyl absorption peaks and the appearance three peaks in the region 3320–3127 cm −1 because of NH 2 and NH. Also, 1 H NMR exhibited D 2 O exchangeable broad singlet signal at δ 5.62 ppm owing to four exchangeable hydrogens (NH 2 and 2NH), as reported previously . Alternatively, compounds 7a , b were prepared from coupling reaction of 5‐aminopyrazolyl phthalazine 8 , which was synthesized from the reaction of 1 with hydrazine hydrate in EtOH at reflux temperature, with diazotized aromatic amine.…”

“…Brown crystals, yield 79%, mp 255–257°C (EtOH); IR ( ν max , cm −1 ): 3320–3172 m (NH 2 and NH), 1660–1643 (C═O), 1595–1556s (C═N), 1495 (C═C); 1 H NMR (500 MHz, DMSO‐ d 6 ) δ H (ppm): 2.26 (s, 3H, CH 3 ), 5.62 (s, broad, D 2 O exchangeable, 4H, NH 2 , and 2NH, appear together) , 7.17 (d, 2H, J 8 Hz, Ar─H), 7.39 (d, 2H, J 7.5 Hz, Ar─H), 7.82 (dd, 2H, J 9.5, 3.5 Hz, phthalazine‐H), 8.06 (dd, 2H, J 9.5, 3.5 Hz, phthalazine‐H); 13 C NMR (125 MHz, DMSO‐ d 6 ) δ C (ppm): 20.5 (CH 3 ), 115.1, 125.3, 128, 129.3, 129.8, 132.1, 133.5, 139.6, 149.9, 155.7, 158.8 (C═O), 159 (C═O); MS m/z (%): 346 [M‐15] + (2%), 217 (100%); Anal . Calcd for C 18 H 15 N 7 O 2 (361.37): C, 59.83; H, 4.18; N, 27.13, Found: C, 59.71; H, 4.05; N, 26.98%.…”

“…The precipitated product was filtered, washed (EtOH), dried, and recrystallized from EtOH. Colorless powder, (89%), mp ˃300°C (EtOH); IR ( ν max , cm −1 ): 3320–3167 (NH 2 and NH) 1662 (C═O), 1600–1556s (C═N), 1492–1458 (C═C); 1 H NMR (500 MHz, DMSO‐ d 6 ) δ H (ppm): 1.78 (s, 2H, CH 2 ), 6.30 (s, broad D 2 O exchangeable, 3H, NH 2 , and NH, appear together) , 7.79 (m, 2H, phthalazine‐H), 8.05 (m, 2H, phthalazine‐H); 13 C NMR (125 MHz, DMSO‐ d 6 ) δ C (ppm): 23.8 (CH 2 ), 125.4, 125.6, 128.6, 131.9, 132.18, 156.6, 175 (C═O); MS m/z (%): 216.9 [M‐26] + (100%), 161.6 (27%); Anal . Calcd for C 11 H 9 N 5 O 2 (243.23): C, 54.32; H, 3.73; N, 28.79, Found: C, 54.06; H, 3.47; N, 28.68%.…”

Approaches towards the synthesis of 5-aminopyrazoles

“…Beam et al [85] have reported a novel synthesis of 5-aminopyrazoles 155 from polylithiated C (α), N -thiosemicarbazones (X = S) or C (α), N -semicarbazones (X = O). The polylithiated intermediates, prepared from C (α), N -thiosemicarbazones (X = S) or C (α), N -semicarbazones (X = O) 154 and an excess of lithium diisopropylamide (LDA), underwent cyclization and on subsequent hydrolysis gave the 5-aminopyrazole derivatives 155 (Scheme 43).…”

New synthesis of 3-aryl-5-amino-1H-pyrazoles

“…β-Oxo nitriles are prepared in turn by reaction of halo ketones with sodium or potassium cyanide. Other known methods for the preparation of aminopyrazoles are based on intramolecular cyclization of acetophenone thiosemicarbazones [6] and semicarbazones [7,8], reaction of β-amino-β-arylacrylonitrile [9] or α,β-dichloropropionitrile [10] with hydrazines, and decarboxylation of 5-amino-3-arylpyrazole-1-carboxylic acids [3]. Hartmann and Liebscher [5] proposed a procedure for the synthesis of aminopyrazoles via reaction of hydrazine with β-aryl-β-chloroacrylonitriles.…”