S.P. Rekowski, B.K. Kroener, D. Kathuria et al.
Tetrahedron 91 (2021) 132192
3
d
7.98 (d like, J(30-H, 40-H) ¼ 8.8 Hz, 1H, 30-H), 8.04 (bs, 2H, 300-H
4.2.16. (E)-2-((2-bromopyridin-3-yl)methylene)hydrazine-1-
carboximidamide hydrochloride [(E)-(1o)]
3
4
and 400-H), 8.11 (dd like, J(40-H, 30-H) ¼ 8.8 Hz, J(40-H, 60-
4
H) ¼ 2.8 Hz, 1H, 40-H), 8.56 (s, 1H, 2-H), 8.96 (d like, J(60-H, 40-
H) ¼ 2.8 Hz, 1H, 60-H), 12.52 (bs, 1H, 100-H); 13C NMR (150 MHz,
DMSO‑d6)
d
122.70 (C-60), 126.10 (C-40), 130.60 (C-20), 134.19 (C-10),
135.21 (C-30), 144.06 (C-2), 148.0 (C-50), 155.81 (C-200); HRMS (ESI,
[MþH]þ) calculated for [C8H9N4BrCl]þ 285.9334 found 285.9336.
4.2.14. (E)-2-(2-bromo-5-(trifluoromethyl)benzylidene)hydrazine-
1-carboximidamide hydrochloride [(E)-(1m)]
According to general procedure I, 2-bromonicotinaldehyde (3o)
(930 mg, 5 mmol) and aminoguanidine hydrochloride (4) (552 mg,
5 mmol) were reacted. After work-up and purification by recrys-
tallization (EtOH:H2O ¼ 1:1) (E)-2-((2-bromopyridin-3-yl)methy-
lene)hydrazine-1-carboximidamide hydrochloride [(E)-(1o)] was
obtained as a white solid in 76% yield (1.05 g, 3.79 mmol); mp
238e239 ꢀC; IR (ATR) ῦ 3199, 3067, 2921, 1678, 1648, 1591, 1552,
1459,1391,1339,1278,1147,1120,1047, 934, 861, 730 cmꢁ1; 1H NMR
3
7.54 (dd like, J(50-H, 60-H) ¼ 3J(50-H, 40-
According to general procedure I, 2-bromo-5-(trifluoromethyl)
benzaldehyde (3m) (1265 mg, 5 mmol) and aminoguanidine hy-
drochloride (4) (552 mg, 5 mmol) were reacted. After work-up and
purification by recrystallization (EtOH:H2O ¼ 1:1) (E)-2-(2-bromo-
5-(trifluoromethyl)benzylidene)hydrazine-1-carboximidamide hy-
drochloride [(E)-(1m)] was obtained as a white solid in 68% yield
(1.17 g, 3.41 mmol); mp 201e202 ꢀC; IR (ATR) ῦ 3282, 3105, 3016,
2905, 1676, 1636, 1598, 1581, 1454, 1414, 1325, 1259, 1210, 1160,
1114, 1078, 1025, 956, 908, 830 cmꢁ1; 1H NMR (600 MHz, DMSO‑d6)
(600 MHz, DMSO‑d6)
d
H) ¼ 7.7 Hz, 1H, 50-H), 7.99 (bs, 2H, 300-H and 400-H), 8.43 (s, 1H, 2-H),
8.43e8.41 (m, 1H, 40-H), 8.65 (dd like, 3J(60-H, 50-H) ¼ 7.7 Hz, 4J(60-
H, 40-H) ¼ 2.0 Hz 1H, 60-H), 12.47 (bs, 1H, 100-H); 13C NMR (150 MHz,
DMSO‑d6)
d
124.23 (C-50), 130.43 (C-10), 136.95 (C-60), 142.71 (C-2þ0),
143.82 (C-2), 152.08 (C-40), 155.80 (C-200); HRMS (ESI, [MþH] )
calculated for [C9H9N4BrF3]þ 242.0036 found 242.0032.
4.3. Synthesis and characterization of products 2aꢁo
d
7.69 (dd like, 3J(40-H, 30-H) ¼ 8.5 Hz, 4J(40-H, 60-H) ¼ 2.0 Hz, 1H, 40-
H), 7.92 (d like, 3J(30-H, 40-H) ¼ 8.5 Hz, 1H, 30-H), 7.99 (bs, 2H, 300-H
and 400-H), 8.54 (s, 1H, 2-H), 8.60 (d like, 4J(60-H, 40-H) ¼ 2.0 Hz, 1H,
4.3.1. General procedure II for the synthesis of 2aꢁo
A 10 mL pressure glass vial, equipped with a magnetic stir bar,
60-H), 12.49 (bs, 1H, 100-H); 13C NMR (150 MHz, DMSO‑d6)
d 123.70
was charged with
carboximidamide hydrochloride (E)-1 (360
Cs2CO3 (180 mol, 0.5 equiv), DMEDA (108 mol, 0.3 equiv) and CuI
(36 mol, 0.1 equiv). Then DMF (1.5 mL) was added, the vial was
a
(E)-2-(2-bromobenzylidene)hydrazine-1-
(q, 1J(1000-F, C-1000) ¼ 272.5 Hz, C-1000), 124.60 (C-20), 124.68 (q, 3J(1000-F,
C-60) ¼ 4.0 Hz, C-60), 127.89 (q, 3J(1000-F, C-40) ¼ 4.0 Hz, C-40), 128.98
(q, 2J(1000-F, C-50) ¼ 32.6 Hz, C-50), 133.31 (C-10), 134.36 (C-30), 143.78
(C-2), 155.37 (C-200); HRMS (ESI, [MþH]þ) calculated for
[C9H9N4BrF3]þ 308.9957 found 308.9955.
mmol, 1.0 equiv),
m
m
m
sealed and the reaction mixture was stirred vigorously at 120 ꢀC for
5 h. The reaction mixture was allowed to cool down to room
temperature and NH4Cl (~250 mg) was added. The reaction mixture
was transferred to a round bottom flask using ethyl acetate
(3 ꢂ 30 mL). After adding silica gel, the volatiles were removed and
the adsorbed crude product was subjected to column chromatog-
raphy using mixtures of cyclohexane and ethyl acetate as eluents to
afford the corresponding 1H-indazoles 2 in pure form.
4.2.15. (E)-2-(2-bromo-4-(trifluoromethyl)benzylidene)hydrazine-
1-carboximidamide hydrochloride [(E)-(1n)]
4.3.2. 1H-indazole (2a) [18b]
According to general procedure I, 2-bromo-4-(trifluoromethyl)
benzaldehyde (3n) (1265 mg, 5 mmol) and aminoguanidine hy-
drochloride (4) (552 mg, 5 mmol) were reacted. After work-up and
purification by recrystallization (EtOH:H2O ¼ 1:1) (E)-2-(2-bromo-
4-(trifluoromethyl)benzylidene)hydrazine-1-carboximidamide hy-
drochloride [(E)-(1n)] was obtained as a white solid in 67% yield
(1.14 g, 3.33 mmol); mp 216e217 ꢀC; IR (ATR) ῦ 3245, 3122, 2948,
1666,1628,1595,1529, 1458, 1396,1315,1228, 1129,1074,1039, 942,
According to general procedure II, (E)-2-(2-bromobenzylidene)
hydrazine-1-carboximidamide hydrochloride [(E)-(1aa)] (100 mg,
360
mmol), Cs2CO3 (59 mg, 180
mmol), DMEDA (10 mg, 108 mmol)
and CuI (7 mg, 36
mmol) were reacted. After work-up and purifi-
888, 867, 835, 785 cmꢁ1
;
1H NMR (600 MHz, DMSO‑d6)
d
7.79 (d
cation by column chromatography (SiO2; cyclohexane:ethyl
acetate ¼ 1:1) 1H-indazole (2a) was obtained as a white solid in
like, 3J(60-H, 50-H) ¼ 8.2 Hz, 1H, 60-H), 8.01 (bs, 2H, 300-H and 400-H),
8.06 (d like, 4J(30-H, 50-H) ¼ 1.6 Hz, 1H, 30-H), 8.48 (dd like, 3J(50-H,
60-H) ¼ 8.2 Hz, 4J(50-H, 30-H) ¼ 1.7 Hz,1H, 50-H),12.52 (bs,1H,100-H);
75% yield (32 mg, 270
mmol); Rf 0.60 (cyclohexane:ethyl
acetate ¼ 1:1); 1H NMR (500 MHz, DMSO‑d6)
d
7.09 (dt like, 3J(6-H,
13C NMR (150 MHz, DMSO‑d6)
d
123.08 (q, 1J(1000-F, C-1000) ¼ 272.1 Hz,
5-H) ¼ 3J(6-H, 7-H) ¼ 8.0 Hz, 4 J(6-H, 4-H) ¼ 1.9 Hz, 1H, 6-H), 7.33
(dt like, 3J(5-H, 6-H) ¼ 3J(5-H, 4-H) ¼ 8.0 Hz, 4J(5-H, 7-H) ¼ 1.9 Hz,
1H, 5-H), 7.52 (dd like, 3J(4-H, 5-H) ¼ 8.0 Hz, 4J(4-H, 6-H) ¼ 1.9 Hz,
1H, 4-H), 7.75 (dd like, 3J(7-H, 6-H) ¼ 8.0 Hz, 4J(7-H, 5-H) ¼ 1.9 Hz,
1H, 7-H), 8.05 (s, 1H, 3-H), 13.05 (s, 1H, 1-H); 13C NMR (125 MHz,
C-1000), 123.72 (C-60), 124.58 (q, 3J(1000-F, C-30) ¼ 4.3 Hz, C-30), 128.82
(C-1), 129.90 (3J(1000-F, C-50) ¼ 4.3 Hz, C-50), 136.24 (C-20), 143.67 (C-
2), 155.41 (C-200); HRMS (ESI, [MþH]þ) calculated for [C9H9N4BrF3]þ
308.9957 found 308.9954.
15