Thermolysis of 3-alkyl-3-methyl-1,2-dioxetanes: Activation parameters and chemiexcitation yields

Article abstract of DOI:10.1002/hc.1028

3-Methyl-3-(3-pentyl)-1,2-dioxetane 1 and 3-methyl-3-(2,2-dimethyl-1-propyl)-1,2-dioxetane 2 were synthesized in low yield by the α-bromohydroperoxide method. The activation parameters were determined by the chemiluminescence method (for 1 ΔH? = 25.0 ± 0.3 kcal/mol, ΔS? = -1.0 entropy unit (e.u.), ΔG? = 25.3 kcal/mol, k₁ (60°C) = 4.6 × 10^-4s^-1; for 2 ΔH? = 24.2 ± 0.2 kcal/mol, ΔS? = -2.0 e.u., ΔG? = 24.9 kcal/mol, k₁ (60°C) = 9.2 × 10^-4s^-1. Thermolysis of 1-2 produced excited carbonyl fragments (direct production of high yields of triplets relative to excited singlets) (chemiexcitation yields for 1: φ^T = 0.02, φ^S ≤ 0.0005; for 2: φ^T = 0.02, φ^S ≤ 0.0004). The results are discussed in relation to a diradical-like mechanism.

Full text of DOI:10.1002/hc.1028

Heteroatom Chemistry
Volume 12, Number 3, 2001
T
hermolysis of 3-Alkyl-3-Methyl-1,2-
Dioxetanes: Activation Parameters and
Chemiexcitation Yields
Alfons L. Baumstark, Sean L. Anderson, Chariety J. Sapp,
and Pedro C. Vasquez
Department of Chemistry, Center for Biotechnology and Drug Design, Georgia State University,
Atlanta, GA 30303
Received 2 November 2000; revised 22 January 2001
of excited triplets relative to excited singlets) [1].
Historically, two mechanistic extremes have been
proposed [1] to describe the thermal decomposition
ABSTRACT: 3-Methyl-3-(3-pentyl)-1,2-dioxetane 1
and 3-methyl-3-(2,2-dimethyl-1-propyl)-1,2-dioxetane
2
were synthesized in low yield by the ␣-bromohydro-
of simply substituted dioxetanes: (1) concerted and
2) diradical (Scheme 1). The electron-transfer type
peroxide method. The activation parameters were de-
termined by the chemiluminescence method (for 1
DH‡ ס 25.0 ע 0.3 kcal/mol, DS‡ ס מ1.0 entropy unit
(
processes [1,2] that occur for certain peroxides do
not occur readily with simply substituted diox-
etanes. Most mechanistic studies have been inter-
preted to support a diradical-type two-step mecha-
nism [3]. A merged mechanism has also been
proposed [4] based on effect of the degree and pat-
tern of methyl substitution. Previous results on alkyl
dioxetanes have shown that relative stability de-
pended on the steric interactions of the substituents
[3]. We report here the synthesis and characteriza-
tion of two 3,3-disubstituted dioxetanes in which the
effective steric size of one substituent is varied.
(
1
e.u.), DG‡ ס 25.3 kcal/mol, k (60ЊC) ס 4.6 ן
0 s ; for 2 DH‡ ס 24.2 ע 0.2 kcal/mol, DS‡ ס
1
מ4 מ1
מ2.0 e.u., DG‡ ס 24.9 kcal/mol, k (60ЊC) ס 9.2 ן
1
מ4 מ1
1
0 s . Thermolysis of 1–2 produced excited carbonyl
fragments (direct production of high yields of triplets
relative to excited singlets) (chemiexcitation yields for
T
S
T
S
1
: ␾ ס 0.02, ␾ Յ 0.0005; for 2: ␾ ס 0.02, ␾ Յ
0.0004). The results are discussed in relation to a dir-
adical-like mechanism. ᭧ 2001 John Wiley & Sons,
Inc. Heteroatom Chem 12:176–179, 2001
INTRODUCTION
The thermolysis of phenyl-substituted and/or alkyl-
substituted dioxetanes has been shown to produce
carbonyl fragments, one of which may be produced
in an excited state (direct production of high yields
Correspondence to: Alfons L. Baumstark.
Contract Grant Sponsor: Ronald E. McNair Post-baccalaureate
Program (S.A., C.S.).
Contract Grant Sponsor: Alliance for Minority Participation
Program.
Contract Grant Number: OSP-98-01-661-001.
2001 John Wiley & Sons, Inc.
᭧
SCHEME 1
1
76

Thermolysis of 3-Alkyl-3-Methyl-1,2-Dioxetanes: Activation Parameters and Chemiexcitation Yields 177
TABLE 1 Activation Parameters for the Thermolysis of 3-
Alkyl-3-Methyl-1,2-dioxetanes 1 and 2 in Xylenes
RESULTS
-Methyl-3-(3-pentyl)-1,2-dioxetane 1 and 3-methyl-
2,2-dimethyl-1-propyl)-1,2-dioxetane 2 were syn-
thesized in low yield by the Kopecky method [1],
with closure of the corresponding ␣-bromohydro-
peroxides with a base at low temperature (Reaction
3
(
מ1
Diox-
etane 3-Alkyl
DG‡
b
k s
1
a,b
b
DH‡
DS‡e.u. kcal/mol
(60ЊC)
מ4
מ4
1
2
3-pentyl 25.0 ע 0.3 מ1.0
neopentyl 24.2 ע 0.3 מ2.0
25.3 4.6 ן 10
24.9 9.2 ן 10
1
).
a
All errors reported at 95% confidence limits.
b
Calculated at 60ЊC.
TABLE 2 Chemiexcitation Yields for the Thermolysis of
Dioxetanes 1 and 2 in Xylenes
(1)
a
Dioxetane
␾T
␾S
1
2
0.02
0.02
Յ0.0005
Յ0.0004
The ␣-bromohydroperoxides were synthesized by
the Kopecky procedure [1], treatment of the corre-
sponding alkenes with an electrophilic bromine
source in the presence of concentrated hydrogen
peroxide (caution!) at low temperature in fair yield.
The dioxetanes were purified by low-temperature
a
T
S
Instrument calibrated with tetramethyl-1,2-dioxetane: ␾ ס 0.30; ␾
ס 0.002 (DBA/DPA method at 60ЊC); error limits ע 50% of observed
values [5].
cence without affecting the kinetics. The yields of
chemiexcitation generated during dioxetane ther-
molysis were determined by the DBA/DPA (chemi-
luminescence) method [1,5]. For both dioxetanes,
thermolysis directly produced relatively high yields
of excited triplets (␾ ) and low yields of excited sin-
glets (␾ ). The ␾ values for both compounds at 60ЊC
were 2%, while the ␾ values were less than or equal
1
column chromatography and characterized by H
1
3
NMR and C NMR spectroscopy. Dioxetanes 1–2
were further characterized by analysis of their ther-
molysis products; in all cases, only the expected
cleavage products were produced (Reaction 2).
T
S
T
S
(2)
to 0.05%. The results are summarized in Table 2.
DISCUSSION
The rates of thermolysis of dioxetanes 1–2 were
monitored by the decay of chemiluminescence in-
tensity in aerated xylenes with added fluorescers at
constant temperature (ע0.2Њ). The rates of thermal
decomposition were clearly first order for at least
three half-lives and showed no dependence on the
Conformational and steric substituent effects on
dioxetane stability have been extensively investi-
gated [1b]. Extensive studies of the relative stability
of unsymmetric cis/trans pairs of dioxetanes [3a]
and 3,3-cyclic substituted dioxetanes [6] had shown
that steric considerations were important to diox-
etane properties. A key study [3b] on 3-alkyl-3-meth-
yl-1,2-dioxetanes showed that the relative stability
series was: Et 3 Ͻ i-Pr 4 Ͻ t-Bu 5 (see Table 3). The
major effect showed up in the DH‡ terms while little
or no observable trends were noted in the DS‡ terms.
The results showed that the increased stability of the
dioxetanes correlated with increased branching of
the 3-alkyl substituent in the series. Furthermore,
dioxetanes in this series in which the ethyl group was
formally replaced by either n-propyl or n-butyl [3b]
were found to be of the same relative stability (ki-
netically indistinguishable). These were interpreted
to be consistent with steric interactions between the
3-alkyl group(s) and oxygen-2 in a diradical process.
The effective size of substituents in the previous
type or amount of added fluorescer. At 60ЊC, the
מ4 מ1
value of k for dioxetane 1 was 4.6 ע 0.1 ן 10
while that for 2 was 9.2 ע 0.2 ן 10
s ,
1
מ4 מ1
s . The first-
order rate constants (k ) were determined over a
1
5
0ЊC temperature range. Correlation coefficients
were 0.995 or greater for all cases. The activation
parameters were determined by the Arrhenius
method. Dioxetane 1 with the 3-pentyl substituent
was found to be more stable than 2 with the neopen-
tyl group. The activation parameter data with 95%
confidence limits on errors are shown in Table 1.
Without the presence of added fluorescers, the
thermolyses of dioxetanes 1–2 exhibited only weak
chemiluminescence. Addition of 9,10-dibromoan-
thracene (DBA) or 9,10-diphenylanthracene (DPA)
greatly increased the intensity of chemilumines-

1
78 Baumstark et al.
TABLE 3 Activation Parameters for the Thermolysis of 3-
Alkyl-3-Methyl-1,2-dioxetanes 3–5 in Xylenes
Dioxetane Synthesis
a
The following two-step procedure for the synthesis
of 3-methyl-3-(3-pentyl)-1,2-dioxetane 1 was em-
ployed for the preparation of the two dioxetanes. A
מ1
Diox-
etane 3-Alkyl
DG‡
b
k s
1
b
b
DH‡
DS‡e.u. kcal/mol
(60ЊC)
5
0 mmol sample of 3-ethyl-2-methyl-1-pentene was
מ3
מ4
מ4
3
4
5
Ethyl
Isopropyl 24.3 ע 0.3 מ2.6
t-Butyl 25.7 ע 0.3 מ0.2
23.9 ע 0.2 מ2.7
24.8 1.0 ן 10
25.2 5.8 ן 10
25.8 2.4 ן 10
converted to the ␣-bromohydroperoxide by the Ko-
pecky procedure [1]. The ␣-bromohydroperoxide, 1-
bromo-3-ethyl-2-hydroperoxy-2-methylpentane,
a
a
Recalculated parameter data from reference 3b.
b
clear, viscous oil (caution!) was purified by low tem-
All errors reported at 95% confidence limits; calculated at 60ЊC.
perature (מ78ЊC) column chromatography (silica
1
gel, pentane/dichloromethane) (yield ϳ60%):
H
NMR (CDCl ) d 0.98 (t, 6H); d 1.19 (s, 3H); d 1.22 (m,
3
study was limited [3b]. In the present study, the 3-
alkyl substituents are larger both in total number of
atoms and effective size. Surprisingly, the larger al-
kyl groups in dioxetanes 1 and 2 have little or no
effect over those of the appropriate model com-
pounds. Thus, dioxetane 1 with a 3-pentyl substitu-
ent has activation parameter data essentially iden-
tical to that of 4. Similarly, dioxetane 2 with a
neopentyl group has essentially the same stability as
that of 3 with an ethyl substituent. Clearly, the larger
4
H); d 1.66 (m, 1H); d 3.63–3.73 (AB, 2H); d 7.82 (br
1
3
s, 1H); C NMR (CDCl ) d 13.31, 13.53, 16.80, 22.06,
3
2
3.18, 38.69, 45.20, 85.65; for 1-bromo-2-hydrope-
1
roxy-2,3,3-trimethylbutane (yield ϳ65%): H NMR
(
(
CDCl ) d 1.01 (s, 9H), 1.36 (s, 3H), 1.50 (d, 1H), 1.81
3
1
3
d, 1H), 3.52 (AB, 2H), 7.68 (s, 1H); C NMR (CDCl )
3
d 21.32, 31.12, 31.34, 40.57, 46.84, 83.88. Active ox-
ygen content was determined to be 87 ע 6%.
The purified ␣-bromohydroperoxide (14 mmol)
(caution!) was placed in 20 mL of methylene chlo-
3-alkyl groups in 1 and 2 do not lead to increased
ride with rapid magnetic stirring and cooled by an
ice bath. A solution of 5.0 g of potassium hydroxide
in 10 mL of cold, deionized water was added drop-
wise (5 minutes) to the ␣-bromohydroperoxide so-
lution to yield a two-phase mixture. This mixture
was stirred in an ice bath (ϳ0ЊC) for 2 hr. The pro-
gress of the reaction was monitored by the amount
of light produced by an aliquot of the organic layer.
After the organic phase was separated, additional ex-
tractions of the aqueous layer with methylene chlo-
ride were required to increase the yields of the diox-
etanes. The pale yellow organic layers were
combined, dried over magnesium sulfate, and fil-
tered. The solvent was removed under reduced pres-
sure, and the dioxetane was purified by column chro-
matography (metal-ion free) at מ78ЊC using a
jacketed 1 cm i.d. column packed with 20 g of silica
stabilities. This indicates that buttressing (steric) ef-
fects between the large substituents and position-4
groups are not a factor. Furthermore, the correlation
of the relative stabilities of 1 and 2 with the degree
of branching of the 3-alkyl substituent implies that
the conformation of the substituents is such that the
extra atoms do not interact sterically with oxygen-2.
Molecular mechanics calculations [7] have been
shown to be of value in interpreting dioxetane prop-
erties [1b,3a,f]. No torsion angle changes seem to be
involved in the present cases. The results appear to
be consistent with 3,3-interactions.
T
The chemiexcitation yields (ϳ2% ␾ ) are as ex-
pected for disubstituted dioxetanes [1]. The data
suggest that dioxetanes 1 and 2 are undergoing ther-
molysis by the standard diradical-like mechanism.
Work is in progress on dioxetanes with two large
substituents.
gel containing 1% Na EDTA (pentane). The impure
2
dioxetane in approximately 1 mL CCl was added to
4
the column and washed with 50 mL of pentane fol-
lowed by successive 50 mL additions of a 5% meth-
ylene chloride/pentane step gradient. Fractions were
assayed for dioxetane content relative to light inten-
sity by placing a small aliquot of each fraction into
a DBA solution in the chemiluminescence apparatus
at 60ЊC. Fractions containing the most dioxetane
were combined and the solvent removed under re-
duced pressure. The purified dioxetanes 1–2 were
EXPERIMENTAL
1
13
All solvents were of reagent grade. H and C NMR
spectra were recorded on a Varian 300 MHz spec-
trometer. 9,10-Diphenylanthracene (Aldrich) and
9,10-dibromoanthracene (Aldrich) were recrystalli-
zed from xylenes (Aldrich) before use. 3-Ethyl-2-
methyl-1-pentene (Wiley Organics) and 2,4,4-tri-
methyl-1-pentene (Aldrich) were commercially
available and were used without further purification.
CH analyses were carried out, in house, on the ␣-
bromohydroperoxides.
1
13
yellow oils. The purity was checked by H and
C
NMR spectroscopy. Dioxetane samples that were less
than 95% pure were passed through the column a
second time. The overall yield of dioxetane was 1–

Thermolysis of 3-Alkyl-3-Methyl-1,2-Dioxetanes: Activation Parameters and Chemiexcitation Yields 179
2
% in both cases. The dioxetanes were stored in CCl4
mined by the DBA method as 0.30 at 60ЊC. All mea-
surements were carried out at 60ЊC with a constant
at מ30ЊC or lower. Little decomposition was noted
even after several months of storage. The H NMR
data (CDCl ) are: 1 d 0.83 (m, 6H); d 1.17 (m, 4H), d
1
1
2
1
T
S
concentration of dioxetane. The ␾ and ␾ yields
were calculated by a method that has been discussed
in detail [1]. The concentration of dioxetane was de-
3
.52 (s, 3H), d 2.00 (m, 1H), d 4.71 (d, 1H), d 5.06 (d,
1
3
1
H); C NMR (CDCl ) d 12.26, 12.56, 20.02, 20.73,
termined by H NMR spectroscopy vs. concentration
3
6.66, 49.81, 82.40, 90.22; for 2, d 0.99 (s, 9H); d 1.84
of added standard. The experimental error by the
DBA/DPA method is estimated to be ע50% of ob-
served value.
(
s, 3H); d 1.89 (d, 1H), d 1.97 (d, 1H), d 4.80 (d, 1H),
1
3
d 5.22 (d, 1H); C NMR (CDCl ) d 26.19, 30.55, 30.57,
5
3
2.32, 83.40, 88.49.
Product Studies
REFERENCES
The following general procedure was employed for
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etane (ca. 0.2 M) in CCl was heated at 60ЊC in an
NMR sample tube until the yellow color disap-
peared. In all cases, the expected carbonyl fragments
were the sole products detected by NMR spectros-
copy. The formaldehyde generated from the cleavage
of 1 and 2 was not observed. The carbonyl products
were identified by comparison with authentic
samples.
[
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The chemiluminescence monitoring system is essen-
tially identical with that previously described [1].
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was maintained by using a constant temperature
bath. The temperature in the cell (ע0.2ЊC) was
monitored by use of a YSI Model 425C apparatus
with a series 400 probe. The cell was pretreated with
1
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2
vent before use. Kinetic experiments were carried
out employing xylenes (mixture of isomers) as sol-
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מ4
1
0
M to avoid induced decomposition. Experi-
ments carried out without added fluorescer and with
low concentration (Յ10 ) of DBA or DPA were of
the first order for at least three half-lives and showed
no measurable dependence on the type or amount
of added fluorescer. Reproducibility of k values was
מ3
(
1
f) Baumstark, A. L.; Parker, A. N. J Heterocycl Chem
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1
[
4] Adam, W.; Baader, W. J. J Am Chem Soc 1985, 107,
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1
410–416.
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The instrument was calibrated with tetramethyl-1,2-
dioxetane [5] by taking the triplet yield (␾ ) deter-
T