Conjugate addition of electron-rich aromatics to acrolein in the confined space of zeolite Y

Article abstract of DOI:10.1246/cl.2005.708

Acrolein gas was spontaneously entrapped in supercages of NaY zeolite and the sorption was confirmed by solid ¹³C MAS NMR spectra. In the confined cavities, acrolein smoothly underwent conjugate addition with electron-rich aromatics such as ind

Full text of DOI:10.1246/cl.2005.708

7
08
Chemistry Letters Vol.34, No.5 (2005)
Conjugate Addition of Electron-rich Aromatics to Acrolein
in the Confined Space of Zeolite Y
ꢀ
Shouhei Imachi and Makoto Onaka
Department of Chemistry, Graduate School of Arts and Sciences, The University of Tokyo,
Komaba, Meguro, Tokyo 153-8902
(Received February 15, 2005; CL-050204)
Acrolein gas was spontaneously entrapped in supercages of
NaY zeolite and the sorption was confirmed by solid 1 C MAS
NMR spectra. In the confined cavities, acrolein smoothly under-
went conjugate addition with electron-rich aromatics such as in-
doles and anisole.
3
(c)
(
(
b)
a)
Sorption of organic molecules in zeolite has been studied in
order to demonstrate their behavior in the cavities and the avail-
ability of the zeolite cavities for reaction media which induce se-
lective organic reactions. For instance, labile, polar formalde-
hyde was sorbed and preserved in NaY zeolite cavities as a
monomer form for a long period even at ambient temperatures,
and underwent prompt carbonyl-ene reactions with various ole-
1
fins. Similarly, non-polar aromatics such as benzene were en-
2
capsulated in supercages of NaY. We also reported that 1,3-cy-
clopentadiene was trapped in NaY and that the cyclopentadiene
which was highly condensed in the zeolite cavities showed en-
3
Figure 1. 13C NMR spectra of sorbed acrolein. (a) acrolein in
CDCl , (b) acrolein(1.6)@SiO , and (c) acrolein(3.6)@NaY.
hanced Diels–Alder reactivity toward typical dienophiles.
Here we describe sorption of acrolein in zeolite, and the fac-
ile Friedel–Crafts-type alkylations of electron-rich aromatics
with acrolein. Acrolein has a great potential as a C3 source in or-
ganic synthesis, but is often a troublesome reagent to handle ow-
3
2
three sharp peaks were observed in the range of ꢀ 130–210 ppm
1
0
on each spectrum, respectively (Figure 1). From the spectra of
acrolein(3.6)@NaY and acrolein(1.6)@SiO2, it was confirmed
that the sorbed acrolein molecules were present as a monomer.
The different chemical shifts of a formyl carbon at ꢀ 202 ppm
on NaY and 200 ppm on silica envisaged that the sorbed acro-
leins were differently activated on each porous support.
The reaction of acolein(3.0)@NaY with indole proceeded in
CH2Cl2 at room temperature to give 3-(1H-indol-3-yl)propanal
(2) in 58% yield in an exclusive 1,4-fashion (Table 1, Entry 1).
Interestingly, the addition of acrolein to a mixture of unsorbed
NaY and indole in CH2Cl2 was found to produce 2 in almost
the same yield (Entry 2). This is because more polar acrolein
can be trapped into NaY in preference to indole in a CH2Cl2 so-
lution. Thereafter, in the other experiments in Table 1, we adopt-
ed this simpler reaction procedure to omit the pre-sorption of ac-
rolein into supports.
4
ing to a tendency to prompt dimerization or polymerization.
The Friedel–Crafts alkylations have been widely employed in
5
C–C bond formations. If 1,4-addition of aromatics to acrolein
selectively proceeds without concurrent 1,2-addtion, the Frie-
del–Crafts-type alkylation becomes a promising synthetic strat-
egy to produce aromatics with a terminally-functionalized C3
6
side-chain. Denhart and co-workers reported the Friedel–Crafts
alkylation of substituted indoles with acrolein by using an imini-
7
um catalyst. In their study, both a reactant, acrolein, and a prod-
uct, alkylated indole, were not so stable in the presence of tri-
fluoroacetic acid that satisfactory yields and purity were not ob-
tained.
In the present study, as a sorbent and catalyst we used not
only NaX, NaY, and HY zeolites, but also silica as a control sup-
8
port. Acrolein vapor in an N2 flow was passed over a well-dried
support at 273 K. When 3.6 mmol of acrolein was sorbed into
one gram of NaY, which was referred to as acrolein(3.6)@NaY,
the sorption was saturated. On the other hand, one gram of silica
only accommodated 1.6 mmol of acrolein (acrolein(1.6)@SiO2).
With evacuation treatment on acrolein(1.6)@SiO2 under 67 Pa
for 1 h, the sorbed acrolein was completely lost. In contrast, no
loss of acrolein was observed with acrolein(3.6)@NaY under
the same evacuation conditions, suggesting that acrolein has
strong interaction with sodium ions in NaY.
NaY zeolite-catalyzed addition gave the best result among
the catalysts, though silica showed moderate catalysis. In the
.
presence of strong acid catalysts such as HY and BF3 OEt2, in-
dole rapidly disappeared, but 2 was not detected due to instabil-
ity of 1 and 2 in such acidic circumstances. When the addition
was carried out using NaX which has the same porous frame-
work but a different Si/Al ratio from that of NaY, the reaction
gave poor results with only 20% yield.
Substituted indoles also yielded the corresponding adducts
in moderate to good yields depending on substituents (Table 2).
5-Chloroindole with an electron-withdrawing chlorine atom
In the solid C MAS NMR and liquid 13C NMR spectra of
1
3
9
acrolein(3.6)@NaY, acrolein(1.6)@SiO2 and acrolein in CDCl3,
Copyright ꢀ 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.5 (2005)
709
Table 3. Friedel–Crafts alkylations of anisole with acroleina
Table 1. Friedel–Crafts alkylations to acrolein using solid and
a
liquid catalysts
CHO
CHO
OMe
CHO
MeO
NaY (1.0 g)
5
6
reflux, 12 h
CHO
Entry
Catalyst
Yield/%
66 (29)c
ortho:parab
16:84 (16:84)c
18:82
Catalyst
CH2Cl2
r.t.
N
N
H
1
2
NaY
SiO2
1
H
2
5
Entry
Catalyst
Time
Yield/%
a
Anisole (10 mL) was reacted with arolein (1.0 mmol) in
the presence of catalysts (1.0 g) for 12 h. Determined by
H NMR. Reaction time was 6 h.
b
1
2
3
4
5
acrolein(3.0)@NaY
18 h
18 h
5 min
18 h
18 h
58
56
0
20
37
0
1
c
NaY
HY
NaX
SiO2
omy-type reaction without any formation of wastes or branched
alkyl isomers which are often encountered in the Lewis acid-cat-
alyzed Friedel–Crafts alkylation of aromatics with alkyl halides.
In addition, a formyl group on the side-chain can react with var-
ious nucleophiles or be transformed into other functional groups.
Application of the zeolite-catalyzed addition of acrolein to
chemical syntheses is underway.
b
.
6
BF3 OEt2
5 min
a
Acrolein (3.0 mmol) was reacted with indole (1.0 mmol).
Solid catalysts (1.0 g) were dried at 67 Pa and 673 K for 4 h
b
.
and used. BF3 OEt2 (1.0 mmol).
References and Notes
1
a
Table 2. Friedel–Crafts alkylations of indoles with acrolein
T. Okachi and M. Onaka, J. Am. Chem. Soc., 126, 2306
(2004).
R1
R1
CHO
CHO
2
M. Monduzzi, R. Monaci, and V. Solinas, J. Colloid Inter-
face Sci., 120, 8 (1987).
NaY
N
R
CH Cl
N
R
3
4
5
S. Imachi and M. Onaka, Tetrahedron Lett., 45, 4943 (2004).
G. Desimoni and G. Tacconi, Chem. Rev., 75, 651 (1975).
G. A. Olah, R. Krishnamurti, and G. K. S. Prakash, in ‘‘Com-
prehensive Organic Synthesis,’’ ed. by B. M. Trost and I.
Fleming, Pergamon Press, Oxford (1991), Vol. 3, p 293.
M. Strell and A. Kalojanoff, Chem. Ber., 87, 1025 (1954).
D. J. Denhart, R. J. Mattson, J. L. Ditta, and J. E. Macor,
Tetrahedron Lett., 45, 3803 (2004); J. F. Austin and D. W.
MacMillan, J. Am. Chem. Soc., 124, 1172 (2002).
NaX (Molecular sieves 13X powder, Si/Al ¼ 1:4, SA ¼
2
2
3
2
r.t.
2
4
R1
R2
Entry
Time/h
Yield/%
1
2
3
4
5
H
H
Me
OMe
Cl
H
Me
H
H
H
18
18
12
24
3
56
45
56
42
72
6
7
a
Indoles (1.0 mmol) were reacted with acrolein (3.0 mmol) in
the presence of NaY (1.0 g).
8
2
820 m /g, Aldrich Chemical); NaY (HSZ-320NAA,
2
Si/Al ¼ 2:7, SA ¼ 800 m /g, Tosoh Corp); HY (JRC-Z-
2
showed better reactivity than 5-methoxyindole with an electron-
donating group (Entries 4 and 5).
The alkylation of anisole with acrolein was also successful
HY-5.5, Si/Al ¼ 2:8, SA ¼ 570 m /g, provided by the
Catalyst Society of Japan); silica (Silicagel 60, SA ¼ 500
2
m /g, MERCK).
Solid NMR measurements were carried out by means of sin-
ꢁ
in the presence of NaY under reflux at 154 C to afford the con-
9
ꢁ
jugated adduct 6 in 29% yield after 6 h, and 66% yield after 12 h,
respectively (Table 3, Entry 1). Acrolein molecules encapsulat-
ed in the confined nanospace of NaY could survive for a long re-
action period at such high temperatures. By contrast, SiO2 only
gave a poor yield of 5% after 12 h (Entry 2). To our knowledge,
there have been no reports on direct alkylation of benzene deriv-
atives using acrolein as an electrophile.
A typical procedure is described for the reaction of indole
with acrolein: to a mixture of indole (1.0 mmol) and NaY zeolite
1.0 g) in CH2Cl2 (10 mL) at room temperature (r.t.) was added
gle pulse direct excitation with proton decoupling (90
pulse = 5 ms, 5-s pulse delay, 1000 scans) and the probe
temperature was maintained at 273 K. Chemical shifts were
referenced to TMS as an internal standard, and sample spin-
ning rates were adjusted to ca. 3 kHz.
10 A broad signal near 110 ppm was inevitably derived from the
carbonaceous components around the sample probe in the
NMR instrument (Chemagnetics CMX-300).
ꢂ1
11 IR (CCl4, cm ): 3061, 2920, 2854, 2816, 2715, 1730;
1
(
H NMR (500 MHz, CDCl3): ꢀ 9.79 (t, J ¼ 1:6 Hz, 1H),
acrolein (3.0 mmol) in N2 atmosphere. The resulting suspension
was stirred for 18 h at r.t. Then, acetonitrile (10 mL) was added
in order to extract products sorbed in NaY zeolite, and the mix-
ture was filtrated and the solvent was removed. The crude prod-
8.03 (br, 1H), 7.57 (d, J ¼ 7:8 Hz, 1H), 7.30 (dd, J ¼ 8:2,
0.9 Hz, 1H), 7.18 (t, J ¼ 7:1 Hz, 1H), 7.12 (t, J ¼ 7:1 Hz,
1H), 6.90 (t, J ¼ 0:9 Hz, 1H), 3.08 (t, J ¼ 7:3 Hz, 2H),
1
3
2.81 (td, J ¼ 7:3, 1.6 Hz, 2H); C NMR (125 MHz, CDCl3):
ꢀ 17.5, 43.8, 112.2, 114.3, 118.0, 122.4, 123.0, 125.0, 128.0,
134.6, 202.4.
1
1
uct was purified by preparative TLC to afford 2 in 56% yield.
The addition of aromatics to acrolein is a 100% atom econ-
Published on the web (Advance View) April 16, 2005; DOI 10.1246/cl.2005.708