Thermal decomposition of 1-(aminophenyl)-5-tert-butyl-4,4-dimethyl-2,6,7-trioxabicyclo[3.2.0]heptanes: Unusual O-O bond cleavage competing with normal fragmentation of 1,2-dioxetanes

Article abstract of DOI:10.1039/a806823b

A dioxetane (ortho-3a) decomposes thermally to give the normal carbonyl product while dioxetanes (ortho-3b-c) decompose at low temperature to afford heterocycles 6 and 7 in high yields.

Full text of DOI:10.1039/a806823b

Thermal decomposition of 1-(aminophenyl)-5-tert-butyl-4,4-dimethyl-
2,6,7-trioxabicyclo[3.2.0]heptanes: unusual O–O bond cleavage competing with
normal fragmentation of 1,2-dioxetanes
Masakatsu Matsumoto,* Hiroyuki Murakami and Nobuko Watanabe
Department of Materials Science, Kanagawa University, Tsuchiya, Hiratsuka, Kanagawa 259-12, Japan.
E-mail: matsumo@info.kanagawa-u.ac.jp
Received (in Cambridge, UK) 2nd September 1998, Accepted 21st September 1998
A dioxetane (ortho-3a) decomposes thermally to give the
normal carbonyl product while dioxetanes (ortho-3b–c)
decompose at low temperature to afford heterocycles 6 and
7 in high yields.
But
O
O
But
O
1O2
X
∆
COBut
X
X
O
O
O
Thermal decomposition of rather simple 1,2-dioxetanes gives in
general two carbonyl products.1 Charge transfer (CT)-induced
decomposition of dioxetanes bearing an electron donor also
affords two carbonyl fragments, although its mechanistic
aspects and accompanying luminescence should be differ-
entiated from those of simple thermolysis.2–4 A dioxetane
2
3
4
a X = NH2
b X = NHMe
c X = NMe2
d X = OMe
e X = H
X = o-NHMe2
X = o-NHMe
Me
N
Me
N
O
O
OH
OH
But
Me2N
NMe2
But
O
O
X
O
O
O
O
5
6
7
Scheme 1
1
bearing p-(N,N-dimethylamino)phenyl groups (1) is a typical
example of species that undergo CT-induced decomposition.5
In the course of our investigations on highly efficient chem-
iluminescent substrates, we found that dioxetanes (ortho-3b–c)
bearing a phenyl substituted with an N-methylamino or N,N-
dimethylamino group at the ortho position suffer unusual
decomposition competing with normal fragmentation, although
their unsubstituted o-amino (ortho-3a), p-amino (para-3), and
m-amino analogues (meta-3) undergo thermal decomposition to
afford normal carbonyl products.
These facts prompted us to next examine thermolysis of ortho-
analogues of 3a–c.
An o-aminophenyl moiety was first expected to induce
decomposition of dioxetanes (ortho-3a–c) into 4 similarly to
para-3a–c. A dioxetane bearing an o-aminophenyl moiety
(ortho-3a) was synthesized from a dihydrofuran (ortho-2a)
similarly to the case of para-3a (62% isolated yield). Dioxetane
(ortho-3a) was as unexpectedly stable as its meta-analogue
(meta-3a), although it decomposed into the normal product
(ortho-4a) exclusively on heating (see Table 1). The result
suggests that the CT from an o-aminophenyl moiety most likely
occurs far less easily than from a p-aminophenyl moiety. The
significant difference in ease of CT may be attributed mainly
not to electronic factors but to the steric characteristics of the
aromatic electron donor: the aryl group for ortho-3a does not
rotate around the C–C bond to the dioxetane ring as freely as
that for para-3a because of steric hindrance by the o-amino
group.§ This tendency was also observed for the o-methoxy
derivative (ortho-3d) which is far more persistent than para-3d,
meta-3d and the parent dioxetane 3e.
When a dihydrofuran (para-2a) (100 mg) was irradiated in
the presence of catalytic amount of tetraphenylporphin (TPP) in
CH2Cl2 (10 ml) with a 940 W Na lamp under O2 atmosphere at
0 °C for 1 h, a dioxetane (para-3a) bearing a p-aminophenyl
group† was selectively produced (Scheme 1), although it
decomposed considerably during isolation by chromatography
(SiO2) (colorless crystals melted at 83.0 °C, 23% yield). Similar
singlet oxygenation of dihydrofurans para-2b and para-2c gave
dioxetanes para-3b (N-methylamino) and para-3c (N,N-dime-
thylamino),‡ respectively. These dioxetanes (para-3a–c) de-
composed via a first-order process to afford the corresponding
keto esters (para-4a–c) exclusively in hot toluene-d8. The
decomposition rates were measured at various temperatures
(70–110 °C) in toluene-d8 and activation parameters for
thermolysis of para-3a–c were estimated as shown in Table 1,
where those for dioxetanes bearing a p-methoxyphenyl (para-
3d) and a phenyl moiety (3e), which were synthesized similarly,
are also cited. Table 1 discloses that (i) the thermal susceptibil-
ity of p-amino derivatives (para-3a–c) is prominent, (ii) the
order of half-life (t1/2) (at 25 °C) is para-3c < para-3b < para-
3a < < para-3d < 3e, and (iii) this order is in good agreement
with the order of formal oxidation potential of the parent arenes
(5) corresponding to dioxetanes (para-3a–e): 5c < 5b < 5a < <
5d < 5e.6 These results are consistent with a report on 1 by
Schaap5 and show that CT-induced decomposition takes place
most likely for a dioxetane bearing an aryl moiety with low
oxidation potential. However, it should be noted that these
marked differences in rates of thermal decomposition of para-3
were not observed for meta-analogues (meta-3a, meta-3d,7 3e):
even meta-3a is very persistent thermally, as shown in Table 1.
Singlet oxygenation (278 °C) of an olefin (ortho-2b)
substituted with an o-(N-methylamino)phenyl group also gave
Table 1 Activation parameters for the thermolysis of 1-aryl-5-tert-butyl-
4,4-dimethyl-2,6,7-trioxabicyclo[3.2.0]heptanes 3a
DEa/kcal
t1/2/years
at 25 °C
E1/2/Vb
of 5
Dioxetane
mol21
log A
para-3a
para-3b
para-3c
para-3d
3e
meta-3a
meta-3d
ortho-3a
ortho-3d
a
28.8
29.1
27.7
30.6
30.2
29.9
30.2
30.1
30.7
12.6
13.4
12.5
13.4
12.8
12.7
12.8
12.9
12.0
4.3
2.0
1.4
27
51
33
50
28
660
0.98
0.77
0.73
1.76
2.38
Thermolysis was carried out in toluene-d8 or in p-xylene-d10
b Oxidation half-wave potential (ref. 6); solvent system: R4N+ClO42. (R =
Bu or Pr)/MeCN, reference electrode = SCE, working electrode = Pt.
.
Chem. Commun., 1998, 2319–2320
2319

the corresponding dioxetane (ortho-3b). The thermal decom-
position of ortho-3b exhibited features completely different
from those for the dioxetanes described above. On standing for
several hours at room temperature in toluene or CDCl3, ortho-
3b changed into an unusual product (6) (pale yellow granules
melted at 59.0 °C)† without any detectable amount of the
normal product (ortho-4b) expected initially. Dioxetane ortho-
3b decomposed, however, into ortho-4b in high yield on
heating in refluxing toluene. It should be noted that both
products 6 and ortho-4b are thermally stable and do not change
into each other upon heating. Thus, we carried out thermolysis
of ortho-3b at various temperatures in toluene-d8 and measured
the product ratio of 6:ortho-4b) by 1H NMR spectroscopy:
6:ortho-4b = 93:7 at 50 °C, 72:28 at 70 °C, 35:65 at 90 °C,
11:89 at 110 °C. These results suggest that decomposition to
ortho-4b (mode A) and unusual decomposition to 6 (mode B)
take place concurrently in a temperature-dependant manner for
dioxetane ortho-3b.
The decomposition of mode B is most likely rationalized by
a mechanism similar to the Adam reaction,9¶ comprising the
intramolecular nucleophilic attack of an N-methylamino group
at the O–O moiety of the dioxetane and successive O–O bond
fission accompanying a proton exchange in an intermediary
twitterion (8, R1 = H, R2 = Me), as illustrated in Scheme 2.
Although the proposed mechanism includes multi-step reac-
tions, the decomposition of ortho-3b to 6 should be essentially
a unimolecular reaction as in the pathway to ortho-4b (mode A).
Consequently, the product ratio (6/ortho-4b) described above
should be equal to the ratio of rate constants (kB/kA) for the
corresponding modes at a given temperature. By plotting log(6/
ortho-4b) vs. 1/T, we estimated differences in activation energy
Ea and log A between modes A and B as DEa = Ea (A) 2 Ea (B)
= 18.9 kcal mol21 and DlogA = logA (A) 2 logA (B) = 11.7.
The result suggests that the mode B requires far a lower
activation energy and proceeds through a transition state far
more highly ordered than mode A. As such in the transition
state, one can image a structure where the o-aminophenyl
moiety lies in or near the plane comprising O–C–C shown as T-
1.
O–O as in the case of ortho-3b to 6; the initially formed
zwitterionic intermediate (8, R1, R2 = Me) may undergo
Stevens-like rearrangement10 to afford 7 as shown in Scheme
2.¶∑
In conclusion, the present results show that, for dioxetanes
bearing a substituted phenyl moiety, a p-amino group accel-
erates significantly decomposition of the dioxetane in the order
of H < OMe < < NH2 < NHMe < NMe2, while meta-
analogues are insensitive to this substituent effect. On the other
hand, o-methylamino and o-dimethylamino groups cause
preferentially unusual decomposition of dioxetane by their
intramolecular nucleophilic attack at O–O of the dioxetane,
though their unsubstituted amino analogue decomposes to give
the normal carbonyl product.
Notes and references
† Structures of all products obtained here were characterized by 1H NMR ,
13C NMR, IR, and mass spectral analysis. Selected data for 6: dH(400 MHz,
CDCl3) 0.92 (s, 9H), 1.22 (s, 3H), 1.54 (s, 3H), 3.14 (s, 3H), 3.72 (qAB, J
7.3, 2H), 4.01 (s, 1H), 6.78 (d, J 7.8, 1H), 7.05 (ddd, J 7.8, 7.3, 1.0, 1H), 7.33
(ddd, J 7.8, 7.3, 1.0, 1H), 7.54 (d, J 7.8, 1H); dC(100 MHz, CDCl3) 21.4,
25.7, 28.2, 39.4, 46.7, 47.6, 80.7, 88.4, 110.8, 119.5, 122.3, 127.5, 127.5,
129.8, 151.8. For 7: dH(400 MHz, CDCl3) 0.70 (br s, 9H), 1.19 (s, 3H), 1.50
(s, 3H), 2.86 (s, 3H), 3.73 (qAB, J 7.8, 2H), 4.40 (s, 1H), 4.42 (qAB, J 7.3,
2H), 6.76 (d, J 8.3, 1H), 6.86 (m, 1H), 7.26 (m, 1H), 7.75 (dd, J 7.8, 1.5, 1H);
dC(100 MHz, CDCl3) 22.7, 26.2, 28.2, 35.1, 40.2, 48.0, 78.5, 79.5, 90.6,
108.0, 112.7, 118.6, 125.2, 129.3, 132.0, 148.9.
‡ Dioxetanes para-3b,c were unstable under the chromatographic condi-
tions, so that the crude para-3b,c including little other than a trace amount
of keto ester (para-4b,c) was used without purification for thermolysis.
§ The rate of the CT-induced decomposition of a dioxetane bearing a
phenoxide anion as an electron donor has been reported to decrease via
restriction of rotation of the aromatic ring (ref. 8).
¶ Nucleophilic cleavage of a dioxetane with an aromatic amine is
unprecedented, although a sec-alkylamine has been reported to cause
decomposition of a dioxetane to yield N,N-dialkyl-O-(2-hydroxyethyl)hy-
droxylamine (Adam reaction) (ref. 9). The possibility cannot be ruled out
that the reaction of ortho-3b to give 6 proceeds by a mechanism including
attack of a diradical formed initially by homolytic O–O bond cleavage on an
amino group, although ortho-3a should also give an analogue of 6 by this
mechanism. The marked difference in decomposition mode between ortho-
3a and ortho-3b is most likely attributed to a difference in nucleophilicity
Finally, we attempted to synthesize a dioxetane (ortho-3c)
bearing an o-(N,N-dimethylamino)phenyl moiety. When singlet
oxygenation of a dihydrofuran (ortho-2c) was carried out
similarly to the case of ortho-2a in CH2Cl2 at 0 °C, ortho-2c
gave none of the expected dioxetane (ortho-3c) but gave instead
an unprecedented oxygenation product 7 (colorless granules,
mp 140.0 °C, 93%)† and a small amount of a keto ester (ortho-
4c) (7%). The low-temperature singlet oxygenation of ortho-2c
gave similar results, so that we could obtain little direct
evidence for formation of a dioxetane (ortho-3c). However, the
reaction is reasonably thought to proceed through an unstable
dioxetane (ortho-3c), because both 7 and ortho-4c are products
in which both carbons in the CNC moiety of the starting
dihydrofuran (ortho-2c) are oxygenated. Formation of the
unique cyclic aminal 7 is probably attributed to an intra-
molecular nucleophilic reaction of a dimethylamino group with
between NH2 and NHMe: the order of nucleophilicity would be NH2
NHMe NMe2. The thermal instability of ortho-3c might be also
rationalized by the high nucleophilicity of the NMe2 group.
<
<
∑ Nucleophilic attack of a tert-alkylamine on a dioxetane has been reported
to lead only to normal carbonyl products through Grob fragmentation (ref.
11) of an intermediary zwitterion (ref. 9). For an intramolecular reaction as
presented here, a zwitterion such as 8 might, however, cause predominantly
Stevens-like rearrangement, because an oxy anion would lie so close to a
methyl of the ammonium ion (ON+Me2) that the oxy anion is able to easily
abstract a methyl proton. The formation of a minor product (ortho-4c) may
be due to Grob fragmentation of 8 and/or direct decomposition of ortho-3c
as in the case of para- and meta-3.
1 A review: C. R. Saha-Moler and W. Adam, Four-membered Rings with
Two Oxygen Atoms in Comprehensive Heterocyclic Chemistry II, ed. A.
Padwa, Pergamon, NY, 1996, vol. 1B, pp. 1041–1082.
2 G. B. Schuster, Acc. Chem. Res., 1979, 12, 366.
3 L. H. Catalani and T. Wilson, J. Am. Chem. Soc., 1989, 111, 2633.
4 F. McCapra, Mechanism in Chemiluminescence and Bioluminescence-
Unfinished Business, in Bioluminescence and Chemiluminescence, ed.
J. W. Hastings, L. J. Kricka and P. E. Stanley, Wiley, NY, 1996, pp.
7–15.
5 K. A. Zaklika, T. Kissel, A. L. Thayer, P. A. Burns and A. P. Schaap,
Photochem. Photobiol., 1979, 30, 35; A. P. Schaap, S. D. Gagnon and
K. A. Zaklika, Tetrahedron Lett., 1982, 23, 2943.
R1
R2
N
O
O
N
R1 = H, R2 = Me
ortho-3b
ortho-3c
O
O
6
But
O
T-1
8
6 H. Siegerman, Oxidation and Reduction Half-Wave Potentials of
Organic Compounds, in Techniques of Electroorganic Synthesis, ed.
N. L. Weinberg, Wiley, NY, 1975, pp. 667–826.
R1 = R2 = Me
7 M. Matsumoto, N. Watanabe, N. C. Kasuga, F. Hamada and K.
Tadokoro, Tetrahedron Lett., 1997, 38, 2863.
8 M. Matsumoto, N. Watanabe, T. Shiono, H. Suganuma and J.
Matsubara, Tetrahedron Lett., 1997, 38, 5825.
9 W. Adam and M. Heil, J. Am. Chem. Soc., 1992, 114, 5591.
10 S. H. Pine, Org. React., 1970, 18, 403.
11 C. A. Grob, Angew. Chem., Int. Ed. Engl., 1969, 8, 535.
CH2
H
–
Me
+
N
O
O
7
But
O
Scheme 2
Communication 8/06823B
2320
Chem Commun., 1998