Reaction between conjugated azoalkenes and pyrazolinones: A precious entry to new conjugated azodiene and asymmetric 4,4′-bipyrazole derivatives

Article abstract of DOI:10.1246/cl.2000.984

The first direct nucleophilic addition under mild reaction conditions of heterocyclic compounds to conjugated azoalkenes is reported. This reaction readily gives rise to new conjugated azodiene or asymmetric 4,4′-bipyrazole derivatives by means of two ind

Full text of DOI:10.1246/cl.2000.984

984
Chemistry Letters 2000
Reaction between Conjugated Azoalkenes and Pyrazolinones: A Precious Entry to New
Conjugated Azodiene and Asymmetric 4,4'-Bipyrazole Derivatives
Orazio A. Attanasi, Paolino Filippone,* Chiara Fiorucci, and Fabio Mantellini
Istituto di Chimica Organica, Università di Urbino, Piazza della Repubblica 13, I-61029 Urbino, Italy
(Received May 8, 2000; CL-000444)
The first direct nucleophilic addition under mild reaction
conditions of heterocyclic compounds to conjugated azoalkenes
is reported. This reaction readily gives rise to new conjugated
azodiene or asymmetric 4,4'-bipyrazole derivatives by means of
two independent pathways.
In the wide scenarious of the azo-ene systems,1–5 conjugated
azodienes are relatively little investigated compounds, in spite of
their potential usefulness in organic synthesis.1–6 Furthermore,
asymmetric 4,4'-bipyrazole derivatives are difficult to prepare by
current synthetic methods reported in the literature.7
We now report the synthesis of new conjugated azodienes
4a–d or asymmetric 4,4'-bipyrazol-4,4'-in-3,3'-ones 5a–b by
unprecedented1–5 direct nucleophilic 1,4-addition of 1-methyl-
3-n-propyl-2-pyrazolin-5-one 2a or 1-phenyl-3-methyl-2-pyra-
zolin-5-one 2b to the azo-ene system of conjugated azoalkenes
1a–c in the presence of strong base anion exchanger resin
Duolite® A102 (Rohm and Haas). This reaction affords firstly
the intermediate CH-hydrazone adducts and then NH-hydra-
zone forms 3a–d in tautomeric equilibrium with the relevant
1
NH-hydrazino forms, as shown by the dissapearance in H-
NMR of the CH (4.37) signal and the appearance of a new NH
(10.32) signal during few hours in the NMR tube.4d,8
Subsequently, the above-mentioned products were
obtained by two independent pathways. In fact, conjugated
azodienes 4 having one of the two conjugated olefinic double
bonds in the heterocycle ring arise by mild oxidation of the
hydrazone derivatives 3 with selenium dioxide at room temper-
ature. Asymmetric 4,4'-bipyrazol-4,4'-in-3,3'-ones derive by
simple treatment of the same hydrazone adducts in methanol
under reflux by means of the intramolecular cyclization of the
hydrazone side-chain in position 4 of the pyrazolinone ring.
The solvolytic cleavage of N-COR1 bond was also observed
(see Scheme 1 and Table 1).8
In conclusion we report here the first direct nucleophilic
addition of heterocyclic compounds to the heterodiene system
of conjugated azoalkenes. While the reaction of conjugated
azoalkenes with activated methylene and methine compounds
was extensively studied showing they are powerful tools in
organic synthesis,2–5 the present findings open a broad field of
further innovative investigations on the chemistry of these ver-
satile intermediates. Indeed, this reaction represents an
unknown, mild and useful entry to a new class of conjugated
azodienes in which one of two ene functions is located in the
pyrazole ring. Moreover, the preparation of asymmetric 4,4'-
bipyrazole derivatives difficult to obtain by other methods is
also reported.
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
985
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This work was supported by financial assistance from the
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delle Ricerche (C.N.R.-Roma).
6
7
References and Notes
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3
8
Typical experimental procedure for the synthesis of 1,4-
adducts 3a–d: To a stirred solution of conjugated azoalkenes
1a–c (1 mmol) in THF (20 ml) was added 1-methyl-3-n-
propyl-2-pyrazolin-5-one 2a or 1-phenyl-3-methyl-2-pyra-
zolin-5-one 2b (1 mmol) and Duolite® A102 (400 mg). The
suspension was allowed to react at room temperature for 1 hr
under magnetic stirring. The product was subsequentially
isolated by column chromatography on silica gel with cyclo-
hexane-ethyl acetate mixtures to give 1,4-adducts 3a–d. 3d:
mp 118-120 °C; 1H-NMR (CDCl3): 1.51 (s, 9 H, CMe3), 2.06
(s, 3 H, Me), 2.24 (s, 3 H, Me), 3.72 (s, 3 H, OMe), 4.37 (s, 1
H, CH), 7.10-7.81 (m, 5 H, Ph), 8.21 (bs, 1 H, NH, D2O
exch.), 10.96 (bs, 1 H, NH, D2O exch.); 13C-NMR
(CDCl3):12.6, 17.2, 26.1, 52.9, 82.8, 93.5, 119.3, 121.7,
126.5, 130.7, 138.6, 147.3, 150.1, 151.5, 153.0, 170.7; MS
m/z (relative intensity) 402 (M+, 14), 346 (74), 329 (9), 302
(15), 287 (22), 270 (100). Anal. Calcd for C20H2605N4: C,
59.69; H, 6.51; N, 13.92; Found: C, 59.71; H, 6.50, N, 13.91.
Typical experimental procedure for the synthesis of conjugated
azodienes 4a–d: To a stirred solution of 1,4-adducts 3a-d (1
mmol) in THF (20 ml) was added selenium dioxide (1 mmol).
The suspension was allowed to react at room temperature for
15 min under magnetic stirring. The products was subsequen-
tially isolated by column chromatography on silica gel with
cyclohexane-ethyl acetate mixtures to give conjugated azodi-
4
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1
enes 4a–d. 4d: mp 152-154 °C; H-NMR (CDCl3): 1.54 (s, 9
H, CMe3), 2.03 (s, 3 H, Me), 2.26 (s, 3 H, Me), 3.96 (s, 3 H,
OMe), 7.09-7.92 (m, 5 H, Ph), 8.67 (b s, 1 H, NH, D2O exch.);
13C-NMR (CDCl3): 13.2, 17.9, 28.1, 53.3, 82.6, 116.7, 125.0,
127.0, 128.8, 137.6, 139.8, 144.7, 146.7, 152.2, 161.9, 166.4;
MS m/z (relative intensity) 400 (M+, 12), 344 (13), 300 (11),
295 (14), 272 (39), 259 (82), 240 (100). Anal. Calcd for
C20H2405N4: C, 59.99; H, 6.04; N, 13.99; Found: C, 59.97; H,
6.05, N, 14.00.
Typical experimental procedure for the synthesis of 4,4'-bipyra-
zol-4,4'-in-3,3'-ones 5a,b: 1,4-Adduct 3a–d (1 mmol) was dis-
solved in methanol (25 ml) and heated under reflux for 3 hr.
The product was subsequently isolated by column chromatog-
raphy on silica gel with ethyl acetate to give 4,4'-bipyrazol-5,4'-
in-5,3'-ones 5a,b. 5b: mp 284-286 °C; 1H-NMR (DMSO): 2.09
(s, 6 H, 2 Me), 7.10-7.81 (m, 5 H, Ph), 10.92 (b s, 3 H, 3 NH,
D2O exch.); 13C-NMR (DMSO): 11.3, 13.0, 93.9, 119.6, 124.7,
128.9, 138.2, 138.5, 147.3, 159.8; MS m/z (relative intensity)
270 (M+, 100). Anal. Calcd for C14H1402N4: C, 62.21; H, 5.22;
N, 11.84; Found: C, 62.19; H, 5.23, N, 11.85.
5