Abstract
An easy and efficient copper-catalyzed reaction for the synthesis
of polysubstituted pyrazoles from phenylhydrazones and dialkyl ethylenedicarboxylates
is described. This reaction can tolerate a range of functionalities,
and the corresponding adducts can be obtained in moderate to good
yields.
Key words
heterocycles - copper catalysis - hydrazones - dialkyl ethylenedicarboxylates - pyrazoles
References and Notes
1a
Lamberth C.
Heterocycles
2007,
71:
1467
1b
Elguero J. In
Comprehensive
Heterocyclic Chemistry
Vol. 5:
Katritzky AR.
Rees CW.
Scriven EFV.
Pergamon;
Oxford:
1966.
1c
Eicher T.
Hauptmann S.
Speicher A.
The Chemistry of Heterocycles
2nd
ed.:
J. Wiley and Sons;
New York:
2003.
p.179
2
Elguero J.
Goya P.
Jagerovic N.
Silva AMS.
Pyrazoles as Drugs: Facts and Fantasies,
In Targets in Heterocyclic Systems Chemistry
and Properties
Vol. 6:
Attanasi OA.
Spinelli D.
Italian
Society of Chemistry;
Rome:
2002.
p.52
3a
Sui Z.
Guan J.
Ferro MP.
Mccoy K.
Wachter MP.
Murray WV.
Singer M.
Steber M.
Ritchie DM.
Argentieri DC.
Bioorg. Med. Chem. Lett.
2000,
10:
601
3b
Bekhit AA.
Abdelaziem T.
Bioorg.
Med. Chem.
2004,
12:
1935
3c
Selvam C.
Jachak SM.
Thilagavathi R.
Chakraborti AK.
Bioorg. Med.
Chem. Lett.
2005,
15:
1793
4
Katoch-Rouse R.
Pavlova LA.
Caulder T.
Hoffman AF.
Mukhin AG.
Horti AG.
J.
Med. Chem.
2003,
46:
642
5a
Stauffer SR.
Coletta CJ.
Tedesco R.
Nishiguchi G.
Carlson K.
Sun J.
Katzenellenbogen BS.
Katzenellenbogen JA.
J. Med. Chem.
2000,
43:
4934
5b
Stauffer SR.
Huang Y.
Coletta CJ.
Tedesco R.
Katzenellenbogen JA.
Bioorg. Med. Chem.
2001,
9:
141
6a
Knorr L.
Ber. Dtsch. Chem. Ges.
1883,
16:
2587
6b
Kost AN.
Grandberg II.
Adv.
Heterocycl. Chem.
1966,
6:
347
7a
Silva VLM.
Silva AMS.
Pinto DCGA.
Cavaleiro JAS.
Elguero J.
Eur. J. Org. Chem.
2004,
4348
7b
Heller ST.
Natarajan SR.
Org.
Lett.
2006,
8:
2675
8a
Huang YR.
Katzenellenbogen JA.
Org. Lett.
2000,
2:
2833
8b
Katritzky AR.
Wang M.
Zhang S.
Voronkov MV.
Steel PJ.
J. Org. Chem.
2001,
66:
6787
8c
Singer RA.
Caron S.
McDermott RE.
Arpin P.
Do NM.
Synthesis
2003,
1727
8d
Aggarwal VK.
De Vicente J.
Bonnert RV.
J. Org. Chem.
2003,
68:
5381
8e
Ahmed MSM.
Kobayashi K.
Mori A.
Org. Lett.
2005,
7:
4487
9
Monteiro N.
Balme G.
Delaunay T.
Org.
Lett.
2010,
12:
3328
10
Moses J.
Spiteri C.
Keeling S.
Org.
Lett.
2010,
12:
3368
11
Wada A.
Okitsu T.
Sato K.
Org.
Lett.
2010,
12:
3506
12a
Trost BM.
Acc. Chem. Res.
2002,
35:
695
12b
Trost BM.
Angew. Chem., Int. Ed. Engl.
1995,
34:
259
13
Winterton N.
Green
Chem.
2001,
3:
G73
14a
Davies HML.
Long MS.
Angew. Chem. Int. Ed.
2005,
44:
3518
14b
Wasa M.
Yu JQ.
J. Am. Chem. Soc.
2008,
130:
14058
14c
Brasche G.
Buchwald SL.
Angew. Chem. Int.
Ed.
2008,
47:
1932
14d
Hamada T.
Ye X.
Stahl SS.
J.
Am. Chem. Soc.
2008,
130:
833
14e
Inamoto K.
Hasegawa C.
Hiroya K.
Doi T.
Org. Lett.
2008,
10:
5147
14f
Reed S.
White MC.
J. Am. Chem. Soc.
2008,
130:
3316
15a
Stahl SS.
Angew. Chem. Int. Ed.
2004,
43:
3400
15b
Tsang WCP.
Munday R.
Brasche G.
Zheng N.
Buchwald LL.
J. Org. Chem.
2008,
73:
7603
15c
Monguchi D.
Fujiwara T.
Furukawa H.
Mori A.
Org. Lett.
2009,
11:
1607
16a
Brasche G.
Buchwald SL.
Angew.
Chem. Int. Ed.
2008,
47:
1932
16b
Ueda S.
Nagasawa H.
Angew. Chem. Int. Ed.
2008,
120:
6511
17a
Yan R.
Huang J.
Luo J.
Wen P.
Huang G.
Liang Y.
Synlett
2010,
1071
17b
Yan R.
Luo J.
Wang CX.
Ma CW.
Huang G.
Liang Y.
J. Org. Chem.
2010,
75:
5395
18
Typical Procedure
for the Synthesis of Pyrazoles
An oven-dried reaction
tube was charged with CuI (3.8 mg, 0.02 mmol), NaOAc (16.4 mg, 0.20
mmol), benzaldehyde phenylhydrazone (1a,
47.0mg, 0.24 mmol), and dimethyl acetylenedicarboxylate (2a, 28.4mg, 0.20 mmol). Then DME (2 mL)
was added to the reaction system. The mixture was stirred at r.t.
for 2 h. After removal of the solvent under reduced pressure, the
crude product was purified by column chromatography on silica gel
(EtOAc-PE, 1:8) to give 3aa (49.0
mg, 73%) as white solid (Table
[²]
, entry 1); mp 152-154 ˚C. ¹H
NMR (400 MHz, CDCl3): δ = 7.75 (dd, J = 7.4, 1.8
Hz, 2 H), 7.54 (dd, J = 8.2,
1.4 Hz, 2 H), 7.50-7.40 (m, 6 H), 3.85 (s, 3 H), 3.82 (s,
3 H). ¹³C NMR (100 MHz, CDCl3): δ = 163.37,
160.64, 151.98, 139.03, 136.82, 131.33, 129.16, 129.06, 128.87,
128.77, 128.16, 124.53, 114.13, 53.11, 52.12. IR (neat): 2952, 1733,
1499, 1447, 1266, 911, 732 cm-¹. HRMS: m/z calcd for C19H16N2O4 [M + H]+: 337.1183;
found: 337.1175.
19
Cacchi S.
Bernini R.
Fabrizi G.
Sferrazza A.
Angew. Chem. Int. Ed.
2009,
48:
8078
