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Chemistry Letters Vol.36, No.1 (2007)
1,3-Dipolar Cycloaddition of Ethyl Diazoacetate to Alkynes in the Pores of Zeolite NaY
Keijiro Kobayashi, Yuta Igura, Shouhei Imachi, Yoichi Masui, and Makoto Onakaꢀ
Department of Chemistry, Graduate School of Arts and Sciences, The University of Tokyo,
Komaba, Meguro-ku, Tokyo 153-8902
(Received October 27, 2006; CL-061270; E-mail: conaka@mail.ecc.u-tokyo.ac.jp)
Zeolite NaY promotes 1,3-dipolar cycloaddition of ethyl
(a)
diazoacetate to alkynes having an electron-withdrawing group
to afford the corresponding functionalized pyrazoles in high
yields. The activation of the dipolarophile inside the pores of
NaY is proposed based on the 13C MAS NMR analysis.
Crystalline aluminosilicates, zeolites, have been utilized as
catalysts mainly in the petrochemical industry for a long time.
Recently, we have found that zeolites can not only preserve
unstable, small organic molecules, but also activate them for
the unique C–C bond formation for fine chemicals synthesis.
For instance, labile formaldehyde stayed within zeolite NaY
in the monomer form for at least 30 days even at ambient
temperature, and the adsorbed formaldehyde reacted with olefins
through the carbonyl–ene reaction to afford homoallylic alco-
hols.1 Similarly, acrolein adsorbed in NaY underwent conjugate
additions of electron-rich aromatics.2
(b)
Figure 1. 13C NMR of ethyl diazoacetate: (a) N2CHCO2Et ad-
sorbed in NaY, (b) ethyl diazoacetate in CDCl3.
As part of our continued interest in chemical behavior of
labile molecules inside the zeolite pores, we report here the
reaction of ꢀ-diazoacetate with electron-deficient alkynes to
pyrazoles via 1,3-dipolar cycloaddition3 with the aid of NaY.
Actually, the reaction of diazocarbonyl compounds with alkynes
is difficult to perform compared with that of electron-rich di-
azocompounds with alkynes, and a single success in the reaction
has been made by Li and Jiang by using a Lewis acid catalyst,
indium chloride in water.4 They mentioned that the reaction
hardly proceeded in normal organic solvents.4 Our strategy is
that if we take advantage of hydrophilic nature of zeolite, the
pyrazole formation would be successful in the pores of NaY.
Although diazoacetate is recognized a relatively stable diazo
compound, we at first checked whether or not diazoacetate could
be intact upon contact with NaY because NaY has weakly acidic
protons: We adsorbed vaporized ethyl diazoacetate (1.4 mmol)
in NaY zeolite (1 g), and analyzed the sample by NMR.5
In 13C MAS NMR,6 the carbon peaks of ethyl diazoacetate in
NaY appeared at 15(CH3), 48(CH), 64(CH2), and 172(C=O)
ppm, respectively (Figure 1a). As compared with the spectra
in CDCl3 (Figure 1b), the peak of the C=O was intensified as
well as shifted to the downfield by ca. 5 ppm, indicating that
the carbonyl group is more polarized in NaY owing to the strong
interaction with sodium ions or the high electrostatic field effects
of the aluminum-rich NaY. Interestingly, the NMR spectra of
ethyl diazoacetate which had been stored in NaY for 3 months
at room temperature (rt) scarcely changed, indicating that
diazoacetate was stabilized in the NaY pores.
SiO2 as well as without solid catalysts (Entries 2 and 3).5 It is
concluded that zeolite is essential for the promotion of the 1,3-
dipolar cycloaddition reaction.
In order to find the optimal zeolite for the reaction, we
screened different zeolites5 using a bulkier, less reactive alkyne
substrate, ethyl 2-butynoate 3 (Table 2). It is interesting to
find that NaY is the best among various ion-exchanged Y-type
zeolites (Entries 1–4), because sodium ions have not been made
much use of in modern organic synthesis. With NaX, Na-MOR
(mordenite), and Na-Beta, only a trace amount of product 4 was
detected (Entries 6–9). Upon contact with proton-exchanged
zeolites such as HY and H-Beta, ethyl diazoacetate decomposed
with generation of nitrogen gas. Interestingly, the use of
zeolite HY gave pyrazole 4 in 3% yield (Entry 5). This is
because HY was prepared from NaY via partial replacement
of Naþ with Hþ, and HY still contained some sodium ions in
the framework.
Now we have discovered that NaY was the use of choice, we
Table 1. 1,3-Dipolar cycloaddition with solid catalysta
Catalyst
CO2Et
EtO2C
H
CO2Et
HN
N
N2CHCO2Et
1
CH2Cl2, rt, 12 h
2
Entry
Catalyst
Yield/%
Secondly, we found that addition of ethyl diazoacetate to a
suspended mixture of 1 and NaY in CH2Cl2, followed by stirring
at rt for 12 h gave pyrazole 2 in 97% yield (Table 1, Entry 1). As
for a solvent for the reaction, CH2Cl2 was superior to AcOEt,
THF, and CH3CN. The reaction was significantly slower with
1
2
3
NaY
SiO2
—
97
19
12
aEthyl propiolate (1 mmol) was treated with ethyl diazo-
acetate (1.5 mmol) with or without a solid catalyst (1 g).
Copyright ꢀ 2007 The Chemical Society of Japan
Kobayashi, Keijiro
