2
Journal of Chemistry
In continuation of our work on pyrazoles [23], herein,
3-(3,4-Dimethoxyphenyl)-1H-pyrazole (P3): yield: 75%;
m. p.: 123–125°C; 1H NMR (500 MHz, DMSO‒d6): δ � 3.78
(3H, s, -OCH3), 3.62 (3H, s, -OCH3), 6.68 (1H, d, J � 7 Hz,
pyrazole), 6.98 (1H, d, J � 7 Hz, pyrazole), 7.33–7.70 (3H, m,
Ar-H), 12.78 (1H, s, NH, D2O exchg.); 13C NMR
(125.76 MHz, DMSO‒d6): δ � 55.9 (C10, C11), 101.8 (C6),
102.0 (C8), 109.2 (C4), 118.0 (C2), 130.1 (C3), 140.4 (C1),
148.6 (C5), 149.2 (C9), 150.5 (C7); MS: m/z � 204.22 [M]+;
analysis: for C11H12N2O2 calcd. C 64.69, H 5.92, N 13.72%;
found C 64.84, H 5.90, N 13.70% [28].
we have synthesized a series of N-arylpyrazoles, which were
derived from substituted enaminones and were found to
possess an interesting profile as antimicrobial agents.
2. Materials and Methods
2.1. Experimental. Solvents were procured from Merck.
+in layer chromatography (TLC) was performed on Silica
gel 60 F254 coated plates (Merck) to check the purity of
compounds. Melting points were determined by using the
Gallenkamp melting point apparatus. 1H and 13C NMR were
recorded in the Bruker NMR 500/700 MHz and 125/
176 MHz spectrophotometers. +e samples were run in
DMSO-d6 with tetramethylsilane (TMS) as an internal
standard. +e molecular masses of compounds were de-
termined by Agilent triple quadrupole 6410 TQ GC/MS
equipped with ESI (electrospray ionization) source. +e
CHN Elementar (Analysensysteme GmbH, Germany) was
used for elemental analysis of the compounds.
4-[4-(1H-Pyrazol-3-yl)phenyl]morpholine (P4): yield:
1
70%; m. p.: 210–212°C; H NMR (500 MHz, DMSO‒d6):
δ � 1.9 (4H, s, 2 × CH2, morpholine), 3.73 (4H, s, 2 × CH2,
morpholine), 6.10 (4H, m, Ar-H), 6.88 (1H, d, J � 7 Hz,
pyrazole), 7.56 (1H, d, J � 7 Hz, pyrazole), 11.80 (1H, s, NH,
D2O exchg.); 13C NMR (125.76 MHz, DMSO‒d6): δ � 48.6
(C10, C11), 66.5 (C12, C13), 114.9 (C2, C6, C8), 126.0 (C4,
C9), 131.3 (C3), 143.3 (C1), 150.6 (C7); MS: m/z � 229.27
[M]+; analysis: for C13H15N3O calcd. C 68.10, H 6.59, N
18.33%; found C 68.36, H 6.60, N 18.40% [29].
1-[4-(1H-Pyrazol-3-yl)phenyl]piperidine (P5): yield:
1
60%; m. p.: 170–172°C; H NMR (500 MHz, DMSO‒d6):
2.2. Synthesis of Substituted Enaminones (1–11). A mixture
of substituted acetophenone (0.02 mol) and dimethyl
formamide-dimethylacetal (DMF-DMA) (II) (0.023 mol)
was refluxed for 12 h under solvent-free condition on a
heating mantle, and then, the mixture was left to cool slowly
at room temperature. +e precipitate was obtained. Diethyl
ether was added to the precipitate, and filtration was per-
formed under vacuum. +e obtained product was recrys-
tallized from absolute ethanol [24].
δ � 1.23 (6H, s, piperidine), 3.16 (4H, s, piperidine), 6.0–6.98
(4H, m, Ar-H), 7.47 (1H, d, J � 7 Hz, pyrazole), 7.63 (1H, d,
J � 7 Hz, pyrazole), 12.8 (1H, s, NH, D2O exchg.); 13C NMR
(125.76 MHz, DMSO‒d6): δ � 24.3 (C12), 25.6 (C13), 49.7
(C10, C11), 101.2 (C2), 116.0 (C6, C8), 126.3 (C4, C9), 151.3
(C3, C1, C7); MS: m/z � 227.30 [M]+; analysis: for C14H17N3
calcd. C 73.98, H 7.54, N 18.49%; found C 73.69, H 7.56, N
18.55%.
3-(2,4-Dimethoxyphenyl)-1H-pyrazole (P6): yield: 80%;
1
m. p.: 125–127°C; H NMR (500 MHz, DMSO‒d6): δ � 3.81
2.3. Synthesis of Pyrazoles (P1–P11). A mixture of enami-
none (0.01 mol) and hydrazine hydrate 99% (0.01 mol) was
refluxed in absolute alcohol for 3 hours. +e mixture was
poured into cold water. +e precipitate was obtained. +e
product was obtained by filtration under vacuum. +e
product was recrystallized from ethanol [25].
(3H, s, -OCH3), 3.83 (3H, s, -OCH3), 6.61 (1H, d, J � 7 Hz,
pyrazole), 6.66 (1H, d, J � 7 Hz, pyrazole), 7.50–7.62 (3H, m,
Ar-H), 12.8 (1H, s, NH, D2O exchg.); 13C NMR
(125.76 MHz, DMSO‒d6): δ � 55.7 (C10), 55.9 (C11), 99.1
(C6), 103.9 (C8), 105.4 (C2, C4), 105.9 (C3), 128.9 (C1),
139.4 (C5), 157.3 (9), 160.6 (C7); MS: m/z � 204.22 [M]+;
analysis: for C11H12N2O2 calcd. C 64.69, H 5.92, N 13.72%;
found C 64.74, H 5.91, N 13.76% [30].
3-(2,4,6-Trimethoxyphenyl)-1H-pyrazole (P1): yield:
1
70%; m. p.: 148–150°C; H NMR (500 MHz, DMSO‒d6):
δ � (3.75 (3H, s, -OCH3), 3.85 (3H, s, -OCH3), 3.92 (3H, s,
-OCH3), 6.15–6.17 (2H, m, Ar-H), 6.80 (1H, d, J � 7 Hz,
pyrazole), 7.79 (1H, d, J � 7 Hz, pyrazole), 11.81 (1H, s, NH,
D2O exchg.); 13C NMR (125.76 MHz, DMSO‒d6): δ � 55.5
(C10), 55.9 (C11, C12), 94.3 (C6), 98.9 (C8), 106.0 (C4),
106.1 (C2), 131.7 (C3), 148.0 (C1), 158.5 (C5), 158.9 (C9),
160.4 (C7); MS: m/z � 234.25 [M]+; analysis: for
C12H14N2O3, calcd. C 61.53, H 6.02, N 11.96%; found C
61.77, H 6.03, N 11.99% [26].
3-(4-Methoxyphenyl)-1H-pyrazole (P7): yield: 90%; m.
p.:126–128°C; 1H NMR (500 MHz, DMSO‒d6): δ � 3.78 (3H,
s, -OCH3), 6.63 (1H, d, J � 7 Hz, pyrazole), 6.99 (1H, d,
J � 7 Hz, pyrazole), 7.55–7.78 (4H, m, Ar-H), 12.8 (1H, s,
NH, D2O exchg.); 13C NMR (125.76 MHz, DMSO‒d6):
δ � 55.5 (C10), 101.7 (C6, C8), 114.4 (C4), 126.9 (C2), 130.1
(C3), 140.4 (C1), 142.2 (C5), 160.4 (C9), 159.1 (C7); MS: m/
z � 174.19 [M]+; analysis: for C10H10N2O calcd. C 68.95, H
5.79, N 16.08%; found C 68.77, H 5.77, N 16.14% [31].
3-(2,5-Dimethoxyphenyl)-1H-pyrazole (P8): yield: 80%;
3-(2,4,5-Trimethoxyphenyl)-1H-pyrazole (P2): yield:
1
1
65%; m. p.: 145–147°C; H NMR (500 MHz, DMSO‒d6):
m. p.: 108–110°C; H NMR (500 MHz, DMSO‒d6): δ � 3.81
δ � 3.78 (3H, s, -OCH3), 3.85 (3H, s, -OCH3), 3.86 (3H, s,
-OCH3), 6.65 (1H, d, J � 7 Hz, pyrazole), 6.78 (1H, d, J � 7 Hz,
pyrazole), 7.31–7.73 (2H, m, Ar-H), 12.80 (1H, s, NH, D2O
exchg.); 13C NMR (125.76 MHz, DMSO‒d6): δ � 56.1 (C10,
C11, C12), 98.7 (C6), 99.1 (C8), 104.2 (C4), 105.4 (C2), 129.1
(C3), 139.5 (C1), 143.2 (C5), 149.8 (C7), 150.7 (C9); MS: m/
z � 234.25[M]+; analysis: for C12H14N2O3 calcd. C 61.53, H
6.02, N 11.96%; found C 61.76, H 6.04, N 11.98% [27].
(3H, s, -OCH3), 3.83 (3H, s, -OCH3), 6.61 (1H, d, J � 7 Hz,
pyrazole), 6.66 (1H, d, J � 7 Hz, pyrazole), 7.50–7.62 (3H, m,
Ar-H), 12.8 (1H, s, NH, D2O exchg.); 13C NMR
(125.76 MHz, DMSO‒d6): δ � 55.7 (C10), 55.9 (C11), 99.1
(C6), 103.9 (C8), 105.4 (C4), 105.9 (C2), 128.9 (C3), 139.4
(C1), 157.3 (C5, C9), 160.6 (C7); MS: m/z � 204.22 [M]+;
analysis: for C11H12N2O2 calcd. C 64.69, H 5.92, N 13.72%;
found C 64.87, H 5.94, N 13.77% [32].