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DOI: 10.1055/s-0029-1216630
Synthesis of Selenium-Substituted Pyrroles and Pyrazol-3-ones
Publication History
Publication Date:
02 April 2009 (online)
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Abstract
An approach to the synthesis of 4-(phenylseleno)pyrroles, 4-(phenylseleno)pyrazol-3-ones, and 4-(1,3-benzoselenazol-2-ylthio)pyrazol-3-ones is described. Their formation passes through hydrazonic intermediates obtained by the reaction between 1,2-diaza-1,3-butadienes and 1-(phenylseleno)ketones, phenylselenol, or 2-mercaptobenzoselenazole, respectively.
Key words
1,2-diaza-1,3-butadienes - Michael additions - selenium - pyrroles - pyrazoles
-
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12a
Synthesis of the α-Seleno Ketones 2a,bCompound 2a Phenyl selenyl chloride (5.0 mmol) was added at r.t. to acetone (4 mL), and the solution was stirred for 30 min. The reaction mixture was poured into H2O and extracted with CH2Cl2. The organic layer was dried over Na2SO4, filtered, and evaporated under vacuum. The crude product 2a (89% yield) was used without further purification.
Compound 2b The phenylselenyl sulfate was generated from (PhSe)2 (1.7 mmol) and (NH4)2S2O8 (2.3 mmol) in MeCN (20 mL) at 80 ˚C. After 30 min the 1-phenylethanone (1.7 mmol) was added. The mixture was stirred overnight at the same temperature, then was poured into an aq solution of NaHCO3 and extracted with CH2Cl2. The organic layer was dried over Na2SO4, filtered, and evaporated under vacuum. The residue was purified by flash chromatography (elution mixture: PE-CH2Cl2 = 85:15) to yield 2b in 40% yield. -
12b Spectral data of 2a and 2b are
identical to those already described in the literature:
Houllemare D.Ponthieux S.Outurquin F.Paulmier C. Synthesis 1997, 101 - 15
Attanasi OA.De Crescentini L.Filippone P.Foresti E.Mantellini F. J. Org. Chem. 2000, 65: 2820 -
18a
Attanasi OA.Filippone P.Mei A.Santeusanio S. Synthesis 1984, 671 -
18b
Attanasi OA.Filippone P.Mei A.Santeusanio S. Synthesis 1984, 873
References and Notes
General Procedure
for the Synthesis of β-(Phenylseleno)-hydrazones 3a,b
To
a magnetically stirred solution of 1,2-diaza-1,3-butadiene 1a as a mixture of E/Z isomers
[¹8]
(1.0
mmol) and 1-(phenyl-seleno)acetone
[¹²]
(2a) or 1-phenyl-2-(phenylseleno)-ethanone
[¹²]
(2b, 1.0 mmol) in THF (5 mL) at r.t., a
catalytic amount (0.1 mmol) of NaH was added. The reaction mixture
was magnetically stirred for 1.0-1.5 h until the disappearance
of the starting 1. β-(Phenylseleno)hydrazones 3a,b were obtained
by chromatography on SiO2 column (elution mixtures: cyclohexane-EtOAc)
and by subsequent crystallization from Et2O-light PE
(40-60). The reaction between 1b,c and 2a,b gave complicated mixtures.
Data for Ethyl 2-[
N-(Aminocarbonyl)ethanehydra-zonoyl]-2,5-dideoxy-3-
Se
-phenyl-3-selenopent-4-ulosonate
(3a)
Yield 294.5 mg (74%)
obtained as yellow solid; mp 148-152 ˚C.
IR (Nujol): νmax = 3420,
3291, 3195, 1765, 1720, 1690 cm-¹. ¹H
NMR (400 MHz, DMSO-d
6): δ = 1.08
(t, 3 H, J = 6.8
Hz), 1.85 (s, 3 H), 2.32 (s, 3 H), 3.44 (d, 1 H, J = 11.6 Hz),
3.97-4.02 (m, 2 H), 4.70 (d, 1 H, J = 11.6
Hz), 6.38 (s, 2 H), 7.38-7.47 (m, 5 H), 9.30 (s, 1 H). ¹³C
NMR (100 MHz, DMSO-d
6): δ = 13.8
(q), 15.2 (q), 27.7 (q), 49.3 (d), 53.8 (d), 60.8 (t), 125.5 (s),
128.8 (d), 129.1 (d), 136.2 (d), 142.4 (s), 156.9 (s), 169.3 (s),
202.0 (s); during the MS analysis, we have observed only the signals
of pyrrole 4a. Anal. Calcd for C16H21N3O4Se:
C, 48.25; H, 5.31; N, 10.55. Found: C, 48.19; H, 5.39; N, 10.63.
General Procedure
for the Synthesis of 4-(Phenylseleno)-pyrroles 4a-c and
2-Oxohydrazones 5a,b
To a magnetically stirred solution
of 1,2-diaza-1,3-butadienes 1a-c as a mixture of E/Z isomers
[¹8]
(2.0
mmol) and 1-(phenylseleno)acetone
[¹²]
(2a, 1.0 mmol) or 1-phenyl-2-(phenylseleno)ethanone
[¹²]
(2b, 1.0 mmol) in THF (5 mL) at r.t., a
stoichiometric amount (1.0 mmol) of NaH was added. The reaction
mixture was magnetically stirred for 6.0-8.0 h until the
disappearance of the starting 1. 4-(Phenyl-seleno)pyrroles 4a-c and
2-oxohydrazones
[¹4]
5a,b were separated
by chromatography on SiO2 column (elution mixtures: cyclohexane-EtOAc),
and they were crystallized from Et2O-light PE (40-60)
or EtOAc-light PE (40-60), respectively.
Ethyl 1-[(Aminocarbonyl)amino]-2,5-dimethyl-4-(phenylseleno)-1
H
-pyrrole-3-carboxylate (4a)
Yield 266.5 mg (70%)
obtained as light yellow solid; mp 182-184 ˚C.
IR (Nujol): νmax = 3518,
3374, 3193, 1727, 1704 cm-¹. ¹H
NMR (400 MHz, DMSO-d
6): δ = 1.04
(t, 3 H, J = 7.2
Hz), 2.10 (s, 3 H), 2.28 (s, 3 H), 4.03 (q, 2 H, J = 7.2 Hz),
6.38 (s, 2 H), 7.15-7.19 (m, 2 H), 7.49-7.53 (m,
2 H), 7.73-7.75 (m, 1 H), 9.29 (s, 1 H). ¹³C
NMR (100 MHz, DMSO-d
6): δ = 10.8
(q), 13.9 (q), 14.2 (q), 58.8 (t), 98.5 (s), 110.3 (s), 118.7 (s),
125.3 (s), 128.2 (d), 128.8 (d), 134.2 (s), 145.9 (d), 156.9 (s),
164.3 (s). MS: m/z (%) = 383
(23) [M+ + 3],
381 (100) [M+ + 1],
379 (57) [M+ - 1],
378 (21) [M+ - 2],
377 (22) [M+ - 3],
375 (2) [M+ - 5].
Anal. Calcd for C16H19N3O3Se:
C, 50.53; H, 5.04; N, 11.05. Found: C, 50.48; H, 5.21; N, 10.96.
General Procedure
for the Synthesis of α-(Phenylseleno)-hydrazones 6a-c
and α-(1,3-Benzoselenazol-2-ylthio)-hydrazones 6d-f
A
solution of 1,2-diaza-1,3-butadienes 1a-c as a mixture of E/Z isomers
[¹8]
(1.0 mmol) and phenylselenol(2c) or 2-mercaptobenzselenazole (2d, 1.0 mmol) in THF (5 mL) was magnetically
stirred at r.t., for 0.1-24.0 h until the disappearance
of the starting 1. Ηydrazones 6a-c were obtained
by chromatography on SiO2 column (elution mixtures: cyclohexane-EtOAc)
and by subsequent crystallization from Et2O-light
PE (40-60), while hydrazones 6d-f were crystallized from Et2O-light
PE
(40-60), after the evaporation of the reaction
solvent. The conversion of α-(1,3-benzoselenazol-2-ylthio)hydrazones 6d-f into
the corresponding hydrazino forms occurred in one week, directly
in the NMR tube, using DMSO-d
6 as
solvent.
Methyl 3-[(Aminocarbonyl)hydrazono]-2-(phenylseleno)-pentanoate (6b)
Yield 247.5 mg (72%)
obtained as white solid; mp 124-126 ˚C.
IR (Nujol): νmax = 3454,
3299, 3191, 1793, 1697 cm-¹. ¹H
NMR (400 MHz, DMSO-d
6): δ = 0.93
(t, 3 H, J = 7.6
Hz), 2.33-2.38 (m, 2 H), 3.60 (s, 3 H), 4.94 (s, 1 H), 6.18
(br s, 2 H), 7.30-7.32 (m, 3 H), 7.54-7.56 (m,
2 H), 9.44 (s, 1 H). ¹³C NMR (100 MHz,
DMSO-d
6) : δ = 9.6
(q), 21.0 (t), 50.1 (d), 52.5 (q), 128.1 (s), 128.2 (d), 129.1 (d),
134.1 (d), 145.8 (s), 156.8 (s), 169.8 (s). MS: m/z (%) = 345
(8)[M+ + 3], 343
(35) [M+ + 1], 341
(17) [M+ - 1], 340
(6) [M+ - 2], 339
(6) [M+ - 3], 337
(1) [M+ - 5], 317
(3), 315 (15), 313 (9), 312 (4), 311 (4), 270 (6), 268 (30), 266
(15), 265 (6), 264 (6), 262 (2), 186 (100). Anal. Calcd for C13H17N3O3Se:
C, 45.62; H, 5.01; N, 12.28. Found: C, 45.48; H, 5.17; N, 12.41.
Ethyl 3-[(Aminocarbonyl)hydrazono]-2-(1,3-benzo-selenazol-2-ylthio)butanoate
(Hydrazono Form of 6d)
Yield 372.5 mg (93%)
obtained as white solid; mp 144-146 ˚C.
IR (Nujol): νmax = 3463,
3313, 3200, 1790, 1692 cm-¹. ¹H
NMR (400 MHz, DMSO-d
6): δ = 1.20
(t, 3 H, J = 7.2
Hz), 1.98 (s, 3 H), 4.16-4.24 (m, 2 H), 5.51 (s, 1 H), 6.28
(br s, 2 H), 7.29 (t, 1 H, J = 8.0
Hz), 7.44 (t, 1 H, J = 8.0 Hz),
7.78 (d, 1 H, J = 7.2
Hz), 8.04 (d, 1 H, J = 6.8
Hz), 9.55 (s, 1 H). ¹³C NMR (100 MHz,
DMSO-d
6) : δ = 13.9
(q), 14.5 (q), 57.4 (t), 61.9 (d), 122.5 (d), 124.6 (d), 125.3 (d),
126.4 (d), 138.3 (s), 140.5 (s), 153.6 (s), 156.6 (s), 166.1 (s),
167.5 (s); MS: m/z (%) = 400
(1) [M+ + 3], 398
(5) [M+ + 1], 396 (2) [M+ - 1],
397 (1) [M+ - 2],
396 (1) [M+ - 3],
328 (9), 326 (45), 324 (19), 323 (8), 322 (8), 320 (1), 313 (31),
311 (100), 309 (60), 308 (24), 307 (23), 305 (3); Anal. Calcd for C14H16N4O3SSe:
C, 42.11; H, 4.04; N, 14.03. Found: C, 42.31; H, 4.11; N, 14.20.
Ethyl 3-[2-(Aminocarbonyl)hydrazino]-2-(1,3-benzo-selenazol-2-ylthio)but-2-enoate
(Hydrazino Form of 6d)
¹H NMR
(400 MHz, DMSO-d
6): δ = 1.11
(t, 3 H, J = 7.2 Hz),
2.30 (s, 3 H), 4.09 (q, 2 H, J = 7.2
Hz), 6.28 (s, 2 H), 7.21 (t, 1 H, J = 8.0
Hz), 7.39 (t, 1 H, J = 8.0
Hz), 7.75 (d, 1 H, J = 6.8
Hz), 7.96 (d, 1 H, J = 8.0
Hz), 8.60 (s, 1 H), 11.08 (s, 1 H). ¹³C
NMR (100 MHz, DMSO-d
6): δ = 14.3
(q), 16.4 (q), 59.9 (t), 82.3 (s), 122.4 (d), 123.7 (d), 125.0 (d),
126.1 (d), 137.8 (s), 156.8 (s), 157.8 (s), 168.7 (s), 172.4 (s),
180.3 (s).
General Procedure
for the Synthesis of 4-(Phenylseleno)-pyrazol-3-ones 7a,b, 8a and
4-(1,3-benzoselenazol-2-ylthio)pyrazol-3-ones 7c,d, 8b
α-(Phenylseleno)-
or α-(1,3-benzoselenazol-2-ylthio)hydra-zones (6a-c and 6d-f,
1.0 mmol) were dissolved in a mixture of THF (5 mL)-MeOH
(5 mL), and a stoichiometric amount of NaH (1.0 mmol) was added.
The reaction mixture was magnetically stirred for 0.1-0.3
h until the disappear-ance of the starting 6.
Pyrazol-3-ones 7a-d were
obtained from 6a,b,d,e, respectively,
while pyrazol-3-ones 8a,b were obtained
from 6c,f, respectively.
Products 7a-d and 8a,b were purified
by chromatography on SiO2 column (elution mixtures: EtOAc-MeOH)
and by subsequent crystallization from Et2O-light
PE (40-60).
5-Ethyl-4-(phenylseleno)-1,2-dihydro-3
H
-pyrazol-3-one (7b)
Yield 252.1 mg (94%)
obtained as white solid; mp 120-122 ˚C.
IR (Nujol): νmax = 3369,
3116, 1735, 1702, 1636 cm-¹. ¹H
NMR (400 MHz, DMSO-d
6): δ = 1.03
(t, 3 H, J = 7.6 Hz),
2.35-2.41 (m, 2 H), 7.18-7.32 (m, 4 H), 7.46 (br
s, 1 H), 7.57-7.59 (m, 1 H), 8.65 (br s, 1 H). ¹³C
NMR (100 MHz, DMSO-d
6): δ = 13.1
(q), 20.8 (d), 125.2 (s), 127.7 (d), 128.9 (d), 129.5 (d), 130.8
(s), 158.6 (s), 164.4 (s). MS: m/z (%) = 270
(20)[M+ + 3], 268
(100) [M+ + 1], 266
(39) [M+ - 1], 265 (19) [M+ - 2],
264 (21) [M+ - 3],
262 (2) [M+ - 5].
Anal. Calcd for C11H12N2OSe: C,
49.45; H, 4.53; N, 10.48. Found: C, 49.49; H, 4.47; N, 10.41.
4-(1,3-Benzoselenazol-2-ylthio)-5-methyl-1,2-dihydro-3
H
-pyrazol-3-one (7c)
Yield 309.1 mg (99%)
obtained as white solid; mp 192-194 ˚C.
IR (Nujol): νmax = 3398,
3328, 1739, 1697, 1673, 1655 cm-¹. ¹H
NMR (400 MHz, DMSO-d
6): δ = 2.02
(s, 3 H), 7.01 (s, 1 H), 7.15 (t, 1 H, J = 7.6
Hz), 7.35 (t, 1 H, J = 8.0
Hz), 7.69 (d, 1 H, J = 8.0
Hz), 7.86 (d, 1 H, J = 8.0 Hz),
8.39 (s, 1 H). ¹³C NMR (100 MHz, DMSO-d
6): δ = 13.4 (q),
80.7 (s), 122.1 (d), 123.2 (d), 124.9 (d), 125.8 (d), 138.0 (s),
153.1 (s), 157.3 (s), 165.8 (s), 184.2 (s). MS: m/z (%) = 313
(28) [M+ + 3], 311
(100) [M+ + 1], 309
(52) [M+ - 1], 308(18) [M+ - 2],
307(18) [M+ - 3],
305 (1) [M+ - 5].
Anal. Calcd for C11H9N3OSSe: C,
42.59; H, 2.92; N, 13.54. Found: C, 42.39; H, 3.01; N, 13.28.
3-Methyl-5-oxo-
N
-phenyl-4-(phenylseleno)-2,5-dihydro-1
H
-pyrazole-1-carboxamide (8a)
Yield 292.1 mg (78%)
obtained as white solid; mp 144-147 ˚C.
IR (Nujol): νmax = 3342,
3191, 1721, 1687 cm-¹. ¹H NMR
(400 MHz, DMSO-d
6): δ = 2.12
(s, 3 H), 6.98 (t, 1 H, J = 7.2
Hz), 7.24-7.28 (m, 5 H), 7.45 (br s, 1 H), 7.51-7.68 (m,
4 H), 11.98 (br s, 1 H). ¹³C NMR (100
MHz, DMSO-d
6): δ = 13.0
(q), 110.4 (s), 119.1 (d), 122.1 (d), 127.7 (d), 127.8 (d), 129.0
(d), 129.5 (d), 130.8 (s), 139.1 (s), 147.3 (s), 154.2 (s), 164.8
(s). MS: m/z (%) = 375
(20) [M+ + 3], 373
(100) [M+ + 1], 371
(41) [M+ - 1], 370
(19) [M+ - 2], 369
(21) [M+ - 3],
367 (3) [M+ - 5].
Anal. Calcd for C17H15N3O2Se: C,
54.85; H, 4.06; N, 11.29. Found: C, 54.96; H, 4.17; N, 11.36.
4-(1,3-Benzoselenazol-2-ylthio)-3-methyl-5-oxo-
N
-phenyl-2,5-dihydro-1
H
-pyrazol-1-carboxamide (8b)
Yield 417.1 mg (97%)
obtained as white solid; mp 246-248 ˚C.
IR (Nujol): νmax = 3351,
3186, 1706, 1683 cm-¹. ¹H NMR
(400 MHz, DMSO-d
6): δ = 2.10
(s, 3 H), 7.05 (t, 1 H, J = 7.6
Hz), 7.17 (t, 1 H, J = 7.6
Hz), 7.32-7.51 (m, 4 H), 7.54 (d, 2 H, J = 8.0
Hz), 7.72 (d, 1 H, J = 8.0
Hz), 7.88 (d, 1 H, J = 8.0
Hz), 12.21 (s, 1 H). ¹³C NMR (100 MHz, DMSO-d
6): δ = 13.4
(q), 81.2 (s), 119.0 (d), 122.2 (d), 122.7 (d), 123.4 (d), 124.9
(d), 125.8 (d), 129.0 (d), 138.0 (s), 138.7 (s), 149.6 (s), 152.8
(s), 157.2 (s), 165.8 (s), 183.3 (s). MS: m/z (%) = 430
(14) [M+ + 3], 428
(45) [M+ + 1], 426
(35) [M+ - 1],
425 (12) [M+ - 2],
424 (13) [M+ - 3],
422 (2) [M+ - 5],
313 (15), 311 (55), 309 (26), 308 (10), 307 (10), 305 (2), 215 (100).
Anal. Calcd for C18H14N4O2SSe:
C, 50.35; H, 3.29; N, 13.05. Found: C, 50.39; H, 3.31; N, 13.23.