The first synthesis of thermally stable acylamino-substituted 1,2-dioxetanes

Article abstract of DOI:10.1246/cl.2006.882

Singlet oxygen added smoothly to N-acyl-5-aryl-4-tert-butyl-3,3-dimethyl-2, 3-dihydropyrroles 1 to give the corresponding bicyclic dioxetanes fused with N-acylpyrrolidine 2, which possessed marked thermal stability. Copyright

Full text of DOI:10.1246/cl.2006.882

8
82
Chemistry Letters Vol.35, No.8 (2006)
The First Synthesis of Thermally Stable Acylamino-substituted 1,2-Dioxetanes
ꢀ
Masakatsu Matsumoto, Yusuke Sano, Nobuko Watanabe, and Hisako K. Ijuin
Department of Chemistry, Kanagawa University, Tsuchiya, Hiratsuka 259-1293
(Received May 10, 2006; CL-060557; E-mail: matsumo-chem@kanagawa-u.ac.jp)
Singlet oxygen added smoothly to N-acyl-5-aryl-4-tert-
butyl-3,3-dimethyl-2,3-dihydropyrroles 1 to give the corre-
sponding bicyclic dioxetanes fused with N-acylpyrrolidine 2,
which possessed marked thermal stability.
Enol ethers undergo 1,2-cycloaddition of singlet oxygen to
give oxy-substituted dioxetanes, the thermal stability of which
ranges in half-life from shorter than a second to more than a hun-
1
–3
dred years at room temperature. On the other hand, there has
been little known of amino-substituted dioxetanes stable enough
to be isolated at room temperature, though singlet oxygen adds
Figure 1. ORTEP view of dioxetane 2a.
1
–5
also easily to the enamine precursors. In the course of our
investigation of novel chemiluminescent compounds, we found
that singlet oxygen added smoothly to N-acyl-5-aryl-4-tert-
butyl-3,3-dimethyl-2,3-dihydropyrroles 1 to give the corre-
sponding acylamino-substituted dioxetanes 2, which possess
marked thermal stability.
Table 1. Thermodynamic parameters for thermal decomposi-
a
tion of acylamino-substituted dioxetanes 2a–2d in p-xylene-d10
z
ꢂ1
z
z
ꢂ1
ꢀH0
/kJ mol
ꢀS0
ꢀG0
/kJ mol
t1=2 at
25 C/y
Dioxetane
ꢂ1
ꢂ1
ꢁ
/J K mol
2
2
2
a
b
c
132
124
122
123
124
17.6
ꢂ5:0
ꢂ7:5
ꢂ5:0
ꢂ4:2
127
126
124
125
125
51.5
33.7
21.7
27.8
49.8
When N-(t-butoxycarbonyl)dihydropyrrole 1a (200 mg) was
irradiated together with a catalytic amount of tetraphenylporphin
(
TPP) in CH2Cl2 (10 mL) with Na-lamp under O2 atmosphere at
C for 1 h, dioxetane fused with pyrrolidine ring 2a was pro-
2
d
ꢁ
0
duced exclusively (Scheme 1). Chromatographic purification
4
a
Time course of thermal decomposition of dioxetanes 2a–2d
of the photolysate gave pure 2a as colorless plates (mp 133.5–
ꢁ
1
was monitored by the use of H NMR.
1
34.0 C, from CH2Cl2–hexane), the structure of which was
1
13
determined by H NMR, C NMR, IR, Ms (EI), and HRMs
6
(
ESI) spectral analysis. Furthermore, X-ray single crystallo-
graphic analysis of 2a was successfully attained as illustrated
in Figure 1.7 Dihydropyrrole-analogs 1b–1d were similarly
dioxygenated with singlet oxygen to afford the corresponding
bicyclic dioxetanes 2b–2d in high isolated yields.
O O
O O
MeO
MeO
O
O
4
The dioxetanes 2a–2d decomposed into the corresponding
keto imides 3a–3d quantitatively by first-order kinetics in p-xy-
Scheme 2.
ꢁ
lene-d10 at 90, 100, and 110 C. Their thermodynamic parame-
z
ters, namely, activation enthalpy (ꢀH0 ), activation entropy
z
marized in Table 1 together with activation parameters for ther-
molysis of related dioxetane 4 fused with a tetrahydrofuran ring
(Scheme 2). Table 1 shows that acylamino-substituted dioxe-
tanes 2a–2d possess marked thermal stability (t1=2 > 20 y at
25 C), and that they and their oxy-analog 4 belong to the class
of dioxetanes with the highest thermal stability among hundreds
z
(
2
ꢀS0 ), activation free energy (ꢀG0 ), and half-life (t1=2) at
ꢁ
8
5 C, were estimated from Arrhenius plots. The results are sum-
ꢁ
O O
YO
1O
1–3
YO
2
of dioxetanes hitherto known. Considering that N-t-butoxy-
R
R
N
carbonyl (N-t-Boc) analogs 2a and 2b are more stable thermally
than N-benzoyl analogs 2c and 2d, it is presumed that the unusu-
al thermal stability of 2 is attributed mainly to the effect of an
annelated five-membered ring, which prevents the dioxetane
ring from cleaving through distortion; an electron-withdrawing
acyl group on a nitrogen should contribute also to the stabiliza-
tion of dioxetanes 2.
N
O
O
2
1
O O
a:Y = Me, R = t-BuO
b:Y = H, R = t-BuO
c:Y = Me, R = Ph
d:Y = H, R = Ph
YO
∆
R
N
It should be noted here that dioxetanes 2a–2d exist as a
mixture of two conformers (40:60–45:55) in a solution, based
O
3
1
on the H NMR analysis. Crystalline 2a used for the X-ray single
1
Scheme 1.
crystallographic analysis displayed H NMR spectrum of con-
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.8 (2006)
883
ment with tetrabutylammonium fluoride in DMSO, to give light
with maximum wavelength at 571 and 600 nm, respectively.
O
MeO
O
t-Bu
N
References and Notes
type A
O
1
A. P. Schaap, K. A. Zaklika, in 1,2-Cycloaddition
Reactions of Singlet oxygen in Singlet Oxygen, ed. by H.
H. Wasserman, R. W. Murray, Academic, NY, 1979,
pp. 173–242.
P. A. Bartlett, M. E. Landis, in The 1,2-Dioxetanes in Singlet
Oxygen, ed. by H. H. Wasserman, R. W. Murray, Academic,
NY, 1979, pp. 173–242.
W. Adam, Four-membered Ring Peroxides; 1,2-Dioxetanes
and ꢀ-Peroxylactones, in The Chemistry of Peroxides, ed.
by S. Patai, Wiley, NY, 1983, pp. 829–920.
O
O
MeO
O
t-Bu
t-Bu
2
a-anti-acyl
N
2
3
O
O
O
O
t-Bu
t-Bu
type B
N
2
a-syn
O
O
MeO
t-Bu
4
5
W. Adam, S. G. Bosio, N. J. Turro, B. T. Wolff, J. Org.
Chem. 2004, 69, 1704, see also refs therein.
2
a-anti-aryl
Scheme 3.
T. Poon, J. Sivaguru, R. Franz, S. Jockusch, C. Martinez, I.
Washington, W. Adam, Y. Inoue, N. J. Turro, J. Am. Chem.
Soc. 2004, 126, 10498.
1
6
Selected data for 2a: H NMR (400 MHz, as a mixture of
7:43 conformational isomers in CDCl3) ꢁH 1.00 (s, 9H),
.05 (s, 9H ꢃ 0:57), 1.06 (s, 9H ꢃ 0:43), 1.12 (s, 3H), 1.40
O
O
O
O
MeO
5
1
t-Bu
t-Bu
YO
N
N
(s, 3H ꢃ 0:57), 1.40 (s, 3H ꢃ 0:43), 3.62 (d, J ¼ 10:0 Hz,
1
10:0 Hz, 1H), 6.82–6.94 (m, 2H), 7.18–7.32 (m, 2H);
H), 3.78 (s, 3H ꢃ 0:43), 3.83 (s, 3H ꢃ 0:57), 4.06 (d, J ¼
O
O
MeO
t-Bu
O
t-Bu
O
1
3
C NMR (125 Hz, as a mixture of 57:43 conformational
isomers in CDCl3) ꢁC 20.6 and 20.6, 25.7 and 25.8, 27.2
and 27.3, 27.6 and 27.7, 37.8 and 37.8, 43.0, 55.3, 62.8,
5
5
a:Y = Me
b:Y = H
6
80.6 and 80.7, 104.5 and 104.6, 106.1 and 106.1, 113.0
and 113.7, 113.8 and 114.5, 119.7 and 121.4, 128.4 and
Scheme 4.
1
m/z, %) 391 (M , 0.3), 359 (0.4), 234 (46), 206 (15), 135
28.6, 139.4 and 139.5, 154.3, 159.0 and 159.1; Ms (EI,
þ
formers similarly to the case mentioned above. Thus, dioxetanes
exist as an equilibrium mixture of conformers in the solution.
2
(
100); HRMs (ESI, m/z) found 414.2223, calcd for
þ
There was little change in the ratio of two conformers through
thermolysis in p-xylene-d10, so that the isomerization between
the conformers should occur easily. If one of the conformers
for 2a possesses the structure 2a-syn like the ORTEP view in
Figure 1, two types of conformational isomerism are possible;
one (type A) occurs around the axis joining t-Boc carbonyl to
nitrogen to give conformers 2a-syn and 2a-anti-acyl, whereas
the other (type B) occurs around the axis joining 3-methoxy-
phenyl to a dioxetane carbon to afford conformers 2a-syn and
C22H33NO5Na [M þ Na] 414.2256.
7
Crystal data for compound 2a: C22H33NO5: Mr 391.51,
3
colorless platelet, 0:30 ꢃ 0:20 ꢃ 0:10 mm , orthorhombic,
space group Pca21 (#29), a ¼ 21:23ð2Þ, b ¼ 9:11ð2Þ, c ¼
˚
˚
3
1
1:208ð9Þ A, V ¼ 2168:9ð46Þ A , Z ¼ 4, Dcalcd ¼ 1:199 g
ꢂ3 ꢁ
cm , T ¼ 173 K, 2ꢂmax ¼ 54:9 , Fð000Þ ¼ 848:00, reflec-
tions
collected/unique
23043/4914
(Rint ¼ 0:048),
ꢂ1
ꢃ(Mo Kꢀ) = 0.84 cm . An empirical absorption correc-
tion was applied which resulted in transmission factors
ranging from 0.8694–1.0000. The data were corrected for
2a-anti-aryl (Scheme 3).
Bicyclic dioxetanes bearing a 4-methoxyphenyl 5a, 4-hy-
Lorentz and polarization effects. Final R indices R1 ¼
droxyphenyl 5b, or 3,5-dimethoxyphenyl 6 can not exhibit the
isomerism due to the rotation of the aromatic ring like the one
between 2a-syn and 2a-anti-aryl (Scheme 4). Thus, dioxetanes
2
0
1
:057 [I > 2ꢄðIÞ], wR2 ¼ 0:145 (all data), GOF on F ¼
˚ ꢂ3
:000, and residual electron density 0.42/ꢂ0:46 e A
CCDC-297571 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/conts/retrieving.html (or from
the Cambridge Crystallographic Data Centre, 12, Union
Road, Cambridge, CB2, 1EZ, UK; fax +44 1223 336033;
or deposit@ccdc.cam.ac.uk).
5
5
a, 5b, and 6 were synthesized similarly to the case of 2a–2d:
9
a and 5b were less stable thermally than 2a–2d, though their
stability was enough to permit handling at room temperature.
1
The H NMR spectra of 5a, 5b, and 6 exhibited that they existed
as one observable conformer but not as a mixture of isomers.
This result suggests strongly that the rotation of the 3-oxyphenyl
group causes the isomerism between 2-syn and 2-anti-aryl, but
not between 2-syn and 2-anti-acyl.
8
9
M. Matsumoto, N. Watanabe, N. C. Kasuga, F. Hamada, K.
Tadokoro, Tetrahedron Lett. 1997, 38, 2863.
Dioxetane 5b decomposed gradually at room temperature.
We should point out finally that acylamino-substituted diox-
etanes, 2b and 2d, underwent intramolecular charge-transfer-
induced chemiluminescent decomposition (CTICL), on treat-
10 Recent reviews: a) M. Matsumoto, N. Watanabe, Bull.
Chem. Soc. Jpn. 2005, 78, 1899. b) M. Matsumoto, J. Photo-
chem. Photobiol., C 2004, 5, 27.
1
0
Published on the web (Advance View) July 1, 2006; doi:10.1246/cl.2006.882