Solid-state photochemistry of crystalline pyrazolines: Reliable generation and reactivity control of 1,3-biradicals and their potential for the green chemistry synthesis of substituted cyclopropanes

Article abstract of DOI:10.1039/c2pp25263e

To expand on the limited number of examples that exist in the literature for the solid-state photodenitrogenation of azoalkanes, a series of crystalline 7-alkyl-2,3,7-triazabicyclo[3.3.0]oct-2-ene-6,8-diones with varying 4,4-substituents were prepared. Th

Full text of DOI:10.1039/c2pp25263e

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PAPER
Solid-state photochemistry of crystalline pyrazolines: reliable generation and
reactivity control of 1,3-biradicals and their potential for the green chemistry
synthesis of substituted cyclopropanes
Saori Shiraki, Cortnie S. Vogelsberg and Miguel A. Garcia-Garibay*
Received 24th July 2012, Accepted 16th August 2012
DOI: 10.1039/c2pp25263e
To expand on the limited number of examples that exist in the literature for the solid-state
photodenitrogenation of azoalkanes, a series of crystalline 7-alkyl-2,3,7-triazabicyclo[3.3.0]oct-2-ene-6,8-
diones with varying 4,4-substituents were prepared. Their photochemical behavior in solution and in the
solid state was dependent on the 4,4-substitution of the 1-pyrazoline ring, with unsubstituted pyrazoline
12 giving a mixture of products both in solution and in the solid state. Diphenyl substituted pyrazolines
13 denitrogenate spontaneously in solution but require light exposure to react quantitatively in the solid
state. t-Butyl-phenyl substituted pyrazolines 14 were shown to denitrogenate both chemo- and
diastereoselectively in solution and in the solid state to yield a single product in quantitative yield.
Introduction
The environmental impact of chemical reactions as they are nor-
mally executed is a growing concern. It has been estimated that
of the non-aqueous material used in pharmaceutical production,
organic solvents account for 80–90% of mass used.1 While some
of the solvent may be recovered and reused, it still constitutes a
large portion of cost that is generated and results in the pro-
duction of waste. With growing demands for more environmen-
tally conscious reactions, those that occur in the solid state and
require no solvents constitute a promising avenue for waste
reduction.2 In this context, we have suggested that photochemi-
cal reactions in crystalline solids can be engineered in a reliable
manner by considering the mechanistic information that deter-
mines the decay of excited states.3–6 We have analyzed the for-
mation of carbenes in crystalline diazo compounds4 and
diazirines,5 and the formation of biradicals and radical pairs in
crystalline ketones.6 We have shown that these reactions tend to
occur with very high selectivities and in high chemical yields,7
and some solid state reactions have been used in the synthesis of
natural products.8 With the purpose of expanding the scope of
solid-state photochemical reactions in green synthesis, we report
here an exploratory investigation on the denitrogenation of pyra-
zolines.9 The purpose of this work is to determine whether or
not a set of homologous pyrazolines will react in the solid state,
and whether the reaction will occur in a selective manner. The
long term vision of this work, as illustrated in Scheme 1, is to
look for a promising strategy for the stereospecific synthesis of
chiral cyclopropanes.
Scheme 1
The photochemistry of pyrazolines was first reported in 1960,
when they were shown to provide a variety of denitrogenated
products.10 While a wide range of azoalkanes has been studied
in solution since that time, only a small number of examples
have been reported in the solid state.11 The first of these studies
explored the photoreactivity of exo- and endo-5-methoxy-2,3-
diazabicyclo[2.2.1]hept-2-ene 1 (Scheme 2).11a In this case,
solution photolysis of exo- and endo-1 gave a mixture of cis-
and trans-2-methoxybicyclo[2.1.0]pentane
2 with a small
amount of biradical disproportionation product (5%). The solid
state photolyses, however, resulted in the retention of the pos-
ition of the methoxy group, with exo-1 giving the cis-diastereo-
mer of the product in a comparatively higher ratio than in
solution.12 A similar selectivity change was also observed for
crystalline endo-1, though with lowered selectivity.
The enhanced selectivity of solid-state photochemical reac-
tions of azoalkanes was also demonstrated by derivative 3.11b
While photolysis in solution gave a mixture of the housane 4
and aziridine 5 (with the product ratio depending on the
solvent),13 the photolysis of a crystalline sample gave denitroge-
nated 4 as the only product, though only in 48% yield. The yield
was increased with the irradiation of a powdered sample, which
Department of Chemistry and Biochemistry, University of California,
Los Angeles, CA 90095-1569, USA. E-mail: mgg@chem.ucla.edu;
Tel: +1 (310) 824 3159
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Scheme 4
Scheme 2
Scheme 5
Scheme 3
N-alkyl maleimides, since the tautomerization of a 1-pyrazoline
to give a 2-pyrazoline with a more strained exocyclic double
bond is unlikely (Scheme 5).18 Therefore, maleimides with
N-methyl (11a), N-butyl (11b), N-benzyl (11c), N-phenyl (11d),
N-4-biphenyl (11e) and N-3,5-dimethoxyphenyl (DMP, 11f )
groups were prepared and subsequently investigated.
gave a 75% yield with complete selectivity for 4. The selectivity
was attributed to the large rotation of the gem-dimethyl groups
necessary for the formation of aziridine 5, which is prevented in
the solid state.
The dipolar cycloaddition reaction of diazomethane with the
series of maleimide derivatives 11a–f in diethyl ether took place
in 1 h to yield a white precipitate. The crystalline products were
obtained in excellent yields (>98%) and were later identified as
pyrazolines 12a–f (Scheme 5). The 1H NMR spectra of the pyra-
zoline product showed four doublet of doublet of doublets at
ca. 3.2, 4.8, 4.9 and 5.7 ppm corresponding to the four hydro-
gens of the pyrazoline ring.
While the photochemical decomposition of diazabicyclo
[2.2.1]hept-2-enes might be used to explore the generality of the
photodenitrogenation reaction in crystalline solids, their syn-
thesis is relatively demanding.11b,14,15 In contrast, the formation
of 1-pyrazolines by the addition of diazoalkanes to activated
alkenes is very simple, and thus we decided to use it for this
study (Scheme 3).
The addition of diphenyldiazomethane to maleimide deriva-
tives 11a–f was also studied to obtain products that may be used
to determine the effect of substituents on the solution and solid-
state photoreactions. The corresponding cycloaddition reactions
to form derivatives 13a–f were much slower relative to the for-
mation of 12a–f and required overnight stirring. Once again, the
products precipitated out as white solids that were nearly insolu-
ble in all solvents, and only sparingly soluble in acetone.
Interestingly the 1H NMR spectra of the dissolved diphenyl-
substituted products indicated the formation of the denitroge-
nated cyclopropane. The spectrum of dissolved 13a matches the
literature spectrum of 3-methyl-6,6-diphenyl-3-azabicyclo[3.1.0]-
hexane-2,4-dione,19 instead of that belonging to the pyrazoline.
The sparse solubility of the pyrazoline solids 13 is in stark
contrast to the previous report of 13d, which describes its solubi-
lity in chloroform.20 The reported melting point of 143° also
does not agree with our findings, which revealed decomposition
for the white precipiate 13d at ca. 151° before melting.
However, the only quantitative technique conducted in the
Preparation and characterization of crystalline pyrazolines
Our initial foray into the synthesis of a set of crystalline pyrazo-
lines was based on the addition of diazomethane to fumarates
and maleates substituted with a number of alkoxy groups. We
reasoned that a variety of such diesters would allow us to obtain
a set of cis- and trans-, and potentially homochiral, pyrazolines
so that we could select those that are crystalline solids for photo-
lysis studies.
Unfortunately, the compounds isolated by addition of diazo-
methane to dimethyl- and dibutyl maleates 6a,b and fumarates
7a,b were shown to isomerize to the corresponding 2-pyrazoline
tautomers 10a,b and thus were not suitable for photolysis studies
(Scheme 4).16 The formation of 10 is in agreement with a pre-
vious study by Swieton et al.,17 where it was found that the
initially formed 1-pyrazolines tautomerize into the 2-pyrazolines,
1
as determined by H NMR and IR spectroscopy. To overcome
this issue, we decided to explore the addition of diazomethane to
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Scheme 6
Fig. 1 13C CP/MAS NMR spectrum of 13a. Asterisks denote spinning
sidebands (MAS = 10 kHz).
previous study was elemental analysis. In our study, solid-state
characterization of the white precipitates resulting from the reac-
tion of diphenyldiazomethane with 11a–f determined that they
are in fact the pyrazolines 13, which subsequently decompose
thermally upon dissolution in the NMR solvent. The identity of
the precipitated solids as the expected pyrazolines was deter-
mined by 13C CP/MAS solid-state NMR analysis. As shown in
Fig. 1 with the spectrum of 13a, the sample contains two non-
equivalent carbonyl peaks at 169 and 172 ppm and aliphatic
signals at 45, 95 and 106 ppm, which are analogous to the
signals for the unsubstituted pyrazolines 12.21 The IR spectra of
the precipitated solids showed two carbonyl signals in the region
of 1701–1718 cm−1, which are also consistent with those deter-
mined for the analogous pyrazolines and shifted with respect to
those of the starting maleimides (1696–1703 cm−1). The yields
for N-phenyl and N-(4-biphenyl) pyrazolines 13d and 13e were
good (>86%) while those for N-benzyl (13c, 69%) and N-methyl
pyrazolines (13a, 37%) were much lower. The addition of
diphenyldiazomethane with the more electron rich benzyl (13b)
and N-DMP (13f) maleimides either did not take place or gave a
mixture of compounds.
Fig. 2 NOESY spectrum of exo-14a (R = Me) illustrating through-
space correlations that establish the steric relation between the t-butyl
group and the two pyrazoline hydrogens. They all are on the convex face
of the bicyclic system.
through space to the nearby bridgehead protons at 3.4 ppm and
5.9 ppm, indicating they are on the same convex side of the
bicyclic system. Cycloaddition reactions of N-methyl (14a) and
N-phenyl (14d) pyrazolines occurred with diastereomeric
excesses, de = 60% and de = 80% respectively. However, the
minor diastereomer could be isolated only for the methyl pyrazo-
line (endo-14a). In the cases of N-benzyl (14c), N-biphenyl
(14e) and N-DMP (14f), the exo-t-butyl pyrazoline formed
In order to also determine whether the photodenitrogenation
reaction proceeds diastereoselectively in the solid state, we pre-
pared adducts of the asymmetric t-butyl-phenyldiazomethane to
maleimides 11a,c–f to form pyrazolines 14a,c–f (Scheme 6).
t-Butyl-phenyldiazomethane was used in hopes that the cyclo-
addition would be diastereoselective since a t-butyl group is
much bulkier than a phenyl group. Five equivalents of t-butyl-
phenyldiazomethane were added to the maleimides and stirred
overnight. The product did not precipitate out, as with 12 and
1
exclusively. The H NMR spectra for these compounds indicate
that the endo-phenyl substituent does not have the freedom to
rotate and the signals for this group at ambient temperature are
very broad, as shown in Fig. 3 (top spectrum) for exo-14a. This
assignment was supported by variable temperature 1H NMR
analysis, which showed that as the temperature is decreased, the
broad signal of the phenyl group (the endo-substituent) splits
into two peaks that correspond to the non-equivalent halves of
the ring (Fig. 3, bottom spectrum).
1
13, and had to be purified by column chromatography. The H
NMR spectra showed the characteristic two doublets at ca. 3.5
and 6.0 ppm corresponding to the bridgehead protons. The pyra-
zolines 14a,d–f formed in moderate to good yields (65–88%).
As predicted, the cycloaddition occurred such that the diaster-
eomer with the t-butyl group in the exo position was the major
diastereomer. The stereochemistry was determined by
2D-NOESY experiments, an example of which is shown for exo-
14a in Fig. 2. The t-butyl protons at 1.0 ppm are correlated
The melting and thermal stability of the pyrazolines were
measured by differential scanning calorimetry (DSC) to deter-
mine whether the photochemical reactions were likely to proceed
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Fig. 3 Variable temperature 1H NMR spectra of exo-14a illustrating
line shape changes in the aromatic region of the spectrum interpreted as
a result from hindered rotation of the endo-phenyl substituent. (Tempera-
tures are uncorrected.)
Fig. 4 DSC traces of (a) N-benzyl 12c, (b) N-phenyl 12d, and (c) N-
(4-biphenyl) 12e, which illustrate the three different thermal behaviours
of the pyrazoline derivatives.
Table 1 The melting and decomposition temperatures (°C) of
pyrazolines 12, 13 and 14
range of ca. 100–150 °C in the solid state. Having only one
phenyl group that can stabilize the radical center, pyrazolines 14
are stable in solution at ambient temperature and react in the
solid state between 150–180 °C.
12 (R = H)
13 (R = Ph)
14 (R = t-Bu, Ph)a
Mp
Decomp.
Mp
Decomp.
Mp
99
Decomp.
152
—
e
a
b
c
d
e
f
93
55
173
154
195
189
197
152
—
—
—
—
—
—
103
—
b
b
f
f
—
e
c
c
Photochemical experiments
101
130
151
146
—
>157d
—
—
>180d
—
168
180
171
e
e
e
e
The denitrogenation of pyrazolines is thought to occur by the
stepwise cleavage of the two C–NvN–C bonds to give a 1,3-bi-
radical (Scheme 7). The initial 1,3-biradical22 formed by photo-
excitation may be either a singlet or a triplet, depending on the
multiplicity of the excited state reactant. Whether a singlet or a
triplet (that eventually intersystem crosses to the singlet state),
the 1,3-biradical recombines to give cyclopropane 15 or under-
goes two different 1,2 hydrogen shifts to give methyl maleimide
16 or methylene succinimide 17. It was hoped that the rigid reac-
tion cavity of the solid state would constrain the biradical to
undergo recombination and to form only cyclopropane 15.
b
b
131
—
>159d
a Values for exo-14a. b Product not isolated. c Not determined due to
insufficient sample. d Samples decompose before complete melting.
e Samples decompose before melting. f Compound not prepared.
in a solid phase or in mixed solid–liquid two phase systems
(Table 1). Based on their melting and decomposition behavior,
the pyrazolines can be categorized into three groups. The first
class includes those (12a–c,f, 14a) that melt before decompos-
ing, as illustrated by the DCS trace of 12c in Fig. 4a. While
melting occurs at 101 °C, the onset of thermal decomposition is
observed at 195 °C. The second class of compounds is rep-
resented by 12d, with a DCS trace shown in Fig. 4b, which
begins to melt but decomposition occurs before the phase tran-
sition is complete. Finally, the third class is represented in
Fig. 4c with pyrazoline 12e, which decomposes well before its
melting point is reached.
Photochemistry of 7-alkyl-2,3,7-triaza-bicyclo[3.3.0]oct-2-ene-
6,8-diones 12a–12f in solution and in the solid state. Photo-
chemical experiments in solution were carried out in dilute
(2 mg ml−1) solutions of pyrazolines in acetonitrile after removal
From the thermal analysis in Table 1 we conclude that the
decomposition temperatures correlate with the 4,4-substituents of
the pyrazolines, which should have a direct effect on the stability
of the radical center at that position. The unsubstituted pyrazo-
line 12 has decomposition temperatures that are higher than
those of the two substituted pyrazolines 13 and 14. The diphenyl
pyrazolines 13 have the lowest decomposition temperatures,
most likely due to the radical stabilizing effects from the two
phenyl groups. The diphenyl pyrazolines are unstable at ambient
temperature in solution and their thermal reaction occurs in the
Scheme 7
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of oxygen by bubbling argon gas for 10 min. The solutions were
exposed to the output of a Hanovia medium pressure mercury
vapor lamp through a quartz filter until all the starting material
had reacted (ca. 2 h). Photochemical reactions in the solid state
were carried out with powdered samples spread on a microscope
slide until the reaction was completed (24–72 h) or until the
solid melted.
Scheme 8
1
Both solution and solid-state reactions were monitored by H
NMR. The radical recombination product 15 is characterized by
a singlet at ca. 2.5 ppm, which is assigned to the bridgehead
protons that are α to the carbonyl. The 1,2 hydrogen shift
product 16 has a doublet at ca. 2.2 ppm for the vinylic methyl
group and a quartet at ca. 6.5 ppm for the vinylic protons, while
17 has apparent triplets at ca. 3.3, 5.6 and 6.3 ppm for the succi-
nimide methylene and the two exocyclic methylene hydrogens.
Some of the compounds are already known and their assignment
was confirmed by comparing their spectra to those available in
the literature. This includes compounds 15a,23 15c,24 16a,25
16c,26 16d,27 17a,27 17b,28 17c and 17d. For new compounds,
the characteristic signals described above were used for identifi-
cation. As shown in Table 2, while cyclopropenes 15a–15f were
the major products in solution, the selectivity of the reaction
varied significantly for different substituents. N-Alkyl substituted
12a–12c gave the corresponding cyclopropenes 15 in yields
above 89%. By contrast, the N-aryl substituted compounds 12d
and 12e react with lower selectivities with the hydrogen shift
products obtained in higher yields. In all cases, as the reaction
progressed, the hydrogen shift products underwent secondary
reactions leaving 15 as the only identifiable product. The analy-
sis of compound 12f was complicated by the overlap of signals
from the starting material and signals from product 16f, but the
formation of 17f in 20% yield is consistent with the results
obtained from 12d and 12e. Also included in the table are the
pyrazoline reactions in the solid state, which proceeded with
higher selectivities than those observed in solution. Reactions
with powdered samples were carried out until some melting was
observed, or until the reaction had gone to completion. Com-
pound 12b, with a low melting point of 55 °C, could not be
reacted at ambient temperature as it immediately started melting.
Compound 12a also started melting at rather low conversion
values, despite a melting point of 93 °C, as expected by the fact
that the hydrogen shift products are liquids at ambient con-
ditions.25,27 All the conversion values are indicated in the table
except when the extent of conversion was limited by sample
melting.
Photochemistry of 4,4-diphenyl-2,3,7-triaza-bicyclo[3.3.0]oct-
2-ene-6,8-diones 13. As indicated in Scheme 8, the solid state
photolysis of the 4,4-diphenyl pyrazolines 13a,c–e gave only the
cyclopropane products 18a,c–e. Solution photolysis could not be
investigated for comparison as the pyrazolines were unstable in
solution and very rapidly decomposed thermally to the same
cyclopropane products. However, the extent of reaction in the
solid state could be monitored qualitatively in situ by 13C CP/
MAS solid-state NMR and ATR-FTIR spectroscopy. While the
conversion of 18 was incomplete, the product, which is highly
soluble in most organic solvents, could simply be washed off the
crystal surface with the unreacted pyrazoline remaining insolu-
ble. The 13C CP/MAS solid-state NMR spectrum of a sample of
13d after photolysis shows that the reaction takes place upon
irradiation in the solid state, and not thermally once dissolved in
acetone (Fig. 5). There is a shift in the carbonyl signals from
169.5 and 172.1 ppm in the pyrazoline to 170.3 and 172.6 ppm
in the cyclopropane and a more significant shift in the aliphatic
signals from 44.8, 95.4 and 106.1 ppm in the pyrazoline to 31.4,
36.7 and 52.4 ppm in the product. While only one carbonyl and
two aliphatic signals are expected for the product in solution
since the molecule is symmetric, the increased number of signals
in the solid-state NMR spectrum suggests that the molecule
occupies a general position of symmetry in the crystal lattice,
which results in magnetic nonequivalence in an asymmetric
environment.
Photochemistry of 4-exo-t-butyl-4-phenyl-2,3,7-triazabicyclo-
[3.3.0]oct-2-ene-6,8-diones 14. Irradiations of t-butyl-phenyl
analogs exo-14a,d–f were also explored in acetonitrile and in the
solid state. While both hydrogen shift products and two dia-
stereomeric cyclopropanes could have been expected in solution,
Table 2 Product ratios in the photolysis of pyrazolines 12 in solution
and in the solid state at 298 K as determined by 1H NMR
CH3CN solution
Solid state
Conv.
Mp
Conv.
15 : 16 : 17
15 : 16 : 17
12a
12b
12c
12d
12e
12f
93
55
101
>180
—
100
100
100
100
100
96
94 : 0 : 6
89 : 0 : 11
94 : 0 : 6
54 : 40 : 6
47 : 41 : 12
76 : —b : 20
17a
0a
100
100
60
12 : 0 : 5
n.a.
100 : 0 : 0
90 : 10 : 0
48 : 8 : 4
82 : —b : 6
131
88
Fig. 5 13C CP/MAS NMR spectra of pyrazoline 13d (top) and the
solid state photolysis product, cyclopropane 18d (bottom).
a Sample melted. b Signals of 15f and 16f are not separable by 1H NMR.
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followed by the solid-state denitrogenation of the resulting pyra-
zolines holds promise for the diastereospecific synthesis of sub-
stituted cyclopropanes. Studies currently in progress in our
group are aimed at testing this hypothesis.
Materials and methods
Scheme 9
N-Alkyl maleimides 12 were prepared according to ref. 29. The
spectral data of 12b,30a 12c24 and 12d31 match the literature
spectra.
only one recombination product, exo-t-butyl cyclopropanes 19a,
d–f, was identified (Scheme 9). The stereochemical identity of
the product was verified by a 2D NOESY NMR measurement,
which showed the correlation of the t-butyl group at ca. 1.0 ppm
with the bridgehead protons at ca. 3.0 ppm (Scheme 9).
Not surprisingly, the solid-state photolysis of pyrazolines
exo-14a,d–f also proceeded very cleanly to give only the cyclo-
propane product 19a,d–f in quantitative yields. That only the
cyclopropane with retention of stereochemistry is formed, both
in solution and in the solid state, indicates that the ring closure
of the biradical is faster than bond rotation, which would result
in the formation of the other cyclopropane diastereomer. It is
also notable that ring closure is faster than the hydrogen shifts.
N-(4-Biphenyl) maleimide 11e
1
Yellow solid. H NMR (CDCl3, 300 MHz): δ 6.87 (2 H, s, 2 ×
vCH), 7.35–7.71 (9 H, m, Ph–Ph) ppm. 13C NMR (CDCl3,
75 MHz): δ 126.4, 127.3, 127.8, 128.0, 129.0, 130.5, 134.4,
140.3, 141.1, 169.7 ppm. IR (solid state): ν 3097.4, 1701.2,
1517.8, 1486.0, 1398.1, 1148.5, 835.8, 689.4 cm−1
.
N-(3,5-Dimethoxyphenyl) maleimide 11f
1
Yellow solid. H NMR (acetone-d6, 300 MHz): δ 3.79 (6 H, s,
2 × OCH3), 6.52 (1 H, t, 2 Hz, Ph), 6.56 (2 H, d, 2 Hz, Ph), 7.00
(2 H, s, 2 × vCH) ppm. 13C NMR (acetone-d6, 75 MHz): δ
55.8, 100.2, 105.9, 134.5, 135.2, 161.8, 170.3 ppm. IR (solid
state): ν 3095.5, 2967.5, 1708.1, 1600.6, 1476.7, 1207.2,
Conclusions
The addition of diazomethane to fumarates 6 and maleates 7
gave 2-pyrazolines 10 instead of the 1-pyrazolines. This tauto-
merization was not observed in the products formed by addition
of diazomethane to N-alkyl maleimides 11a–e, which gave pyra-
zolines 12a–f in nearly quantitative yields (>98%). Analogous
reactions carried out with diphenyldiazomethane to form pyrazo-
lines 13a–f resulted in yields that varied from 0% (N-benzyl
derivative 13b) to 94% (N-phenyl derivative 13d) depending on
the substituent. The resulting 4,4-diphenyl-pyrazolines were
obtained as high-melting crystalline solids insoluble in most
organic solvents, which decompose very rapidly into the corre-
sponding cyclopropane upon dissolution in acetone. Therefore,
the solid-state reactivity of these crystalline pyrazolines was
documented by product characterization using 13C CP/MAS
solid-state NMR and FTIR spectroscopy. Finally, the addition of
asymmetric t-butyl-phenyl-diazomethane takes place diastereo-
selectively with the larger t-butyl group taking the exo configur-
ation in exo-14a–e.
Once the pyrazolines were synthesized, their photolyses were
studied in solution and in the solid state. Unsubstituted pyrazo-
lines 12 are low-melting solids and react to give both recombina-
tion and 1,2 hydrogen shift products in solution and in the solid
state. In agreement with our expectations, reaction selectivities in
the solid state were higher than those in solution, although the
extent of conversion was limited by some sample melting. The
4,4-diphenyl substituted pyrazolines 13 gave the recombination
products in the solid state in quantitative yields but their solution
photolyses could not be analyzed at 298 K due to their thermal
instability in solution. Finally, the photoinduced denitrogenation
of exo-14 also gives recombination products exo-19 both in solu-
tion and in the solid state with retention of configuration. Based
on these results, we propose that a two step procedure based on
the dipolar cycloaddition of diazoalkanes and activated olefins
1149.6, 694.6 cm−1
.
General synthesis of diazomethane
Diazomethane was prepared according to ref. 32. Substituted di-
azomethane was synthesized according to ref. 33 by oxidation of
the appropriate hydrazone.
General procedure for the synthesis of 7-alkyl-2,3,7-triazabi-
cyclo[3.3.0]oct-2-ene-6,8-dione
12. Ethereal
diazomethane
(2 equiv.) was added to N-alkyl maleimide 11 dissolved in
10–25 mL ether. The solution was stirred for 1 h. The solvent
was evaporated and the product was used without further purifi-
cation. The spectral data of 12c34a and d34b match their literature
spectra.
7-Methyl-2,3,7-triazabicyclo[3.3.0]oct-2-ene-6,8-dione 12a.
White solid. 1H NMR (CD3CN, 300 MHz): δ 2.79 (3 H, s,
NCH3), 3.23 (1 H, ddd, 10 Hz, 8 Hz, 4 Hz, CHCHCHaHb), 4.75
(1 H, ddd, 18 Hz, 10 Hz, 2 Hz, CHCHCHaHb), 4.86 (1 H, ddd,
18 Hz, 4 Hz, 2 Hz, CHCHCHaHb), 5.69 (1 H, dt, 8 Hz, 2 Hz,
CHCHCHaHb) ppm. 13C NMR (CD3CN, 75 MHz): δ 25.1, 38.3,
80.7, 95.0, 171.5, 177.4 ppm. IR (solid state): ν 2998.0, 2950.9,
1785.5, 1685.4, 1436.5, 1383.4, 1278.8, 1198.8, 1120.8 cm−1
.
7-Butyl-2,3,7-triazabicyclo[3.3.0]oct-2-ene-6,8-dione 12b.
1
White solid. H NMR (CDCl3, 300 MHz): δ 0.85 (3 H, t, 7 Hz,
CH3CH2), 1.20 (2 H, sextet, 7 Hz, CH3CH2CH2), 1.44 (2 H,
quintet, 7 Hz, CH2CH2CH2), 3.23 (1 H, ddd, 10 Hz, 8 Hz, 3 Hz,
CHCHCHaHb), 3.39 (2 H, t, 7 Hz, CH2CH2), 4.79 (1 H, ddd,
19 Hz, 10 Hz, 2 Hz, CHCHCHaHb), 5.02 (1 H, dt, 19 Hz, 3 Hz,
CHCHCHaHb), 5.69 (1 H, dt, 8 Hz, 2 Hz, CHCHCHaHb) ppm.
13C NMR (CDCl3, 75 MHz): δ 13.5, 19.9, 29.5, 37.3, 39.0,
1934 | Photochem. Photobiol. Sci., 2012, 11, 1929–1937
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General procedure for the synthesis of 7-alkyl-4-t-butyl-4-
phenyl-2,3,7-triazabicyclo[3.3.0]oct-2-ene-6,8-dione 14. Ethereal
t-butyl-phenyl diazomethane (5 equiv.) was added to N-alkyl
maleimide 11 (0.45 mmol) dissolved in 10–25 mL ether and the
solution was stirred overnight. The solution was evaporated. The
product was purified by column chromatography (1 : 1 hexane–
ether) on silica gel.
80.7, 93.5, 169.6, 175.8 ppm. IR (solid state): ν 2958.6, 1776.7,
1699.1, 1438.2, 1395.2, 1347.1, 1129.3 cm−1
.
7-(4-Biphenyl)-2,3,7-triazabicyclo[3.3.0]oct-2-ene-6,8-dione
1
12e. White solid. H NMR (acetone-d6, 300 MHz): δ 3.63 (1 H,
ddd, 11 Hz, 8 Hz, 4 Hz, CHCHCHaHb), 4.98 (1 H, ddd, 19 Hz,
11 Hz, 2 Hz, CHCHCHaHb), 5.13 (1 H, ddd, 19 Hz, 4 Hz, 3 Hz,
CHCHCHaHb), 5.99 (1 H, ddd,
8 Hz, 3 Hz, 2 Hz,
CHCHCHaHb), 7.51–7.78 (9 H, m, Ph–Ph) ppm. 13C NMR
(acetone-d6, 75 MHz): δ 38.8, 81.3, 95.2, 127.9, 128.1, 128.2,
128.6, 129.9, 132.4, 140.9, 142.0, 170.2, 176.4 ppm. IR (solid
state): ν 3032.1, 2993.3, 1717.8, 1698.0, 1522.9, 1487.5,
4-endo-t-Butyl-7-methyl-4-phenyl-2,3,7-triazabicyclo[3.3.0]oct-
2-ene-6,8-dione endo-14a. White solid. 1H NMR (CDCl3,
300 MHz): δ 1.10 (9 H, s, 3 × CH3), 3.00 (3 H, s, NCH3), 3.51
(1 H, d, 9 Hz, CHCH), 5.59 (1 H, d, 9 Hz, CHCH), 7.28–7.46
(5 H, m, Ph) ppm. 13C NMR (CDCl3, 75 MHz): δ 25.5, 28.4,
38.6, 48.1, 95.0, 109.9, 127.8, 127.9, 127.9, 142.1, 169.0,
174.9 ppm. IR (solid state): ν 3058.6, 2962.8, 1783.6, 1703.4,
1394.3, 1196.3, 1177.5, 745.9 cm−1
.
7-(3,5-Dimethoxyphenyl)-2,3,7-triazabicyclo[3.3.0]oct-2-ene-6,8-
1431.0, 1378.5, 1280.4, 1130.6, 705.3 cm−1
.
1
dione 12f. White solid. H NMR (CD3CN, 300 MHz): δ 3.40
(1 H, ddd, 11 Hz, 9 Hz, 3 Hz, CHCHCHaHb), 3.75 (6 H, s, 2 ×
OCH3), 4.85 (1 H, ddd, 19 Hz, 11 Hz, 2 Hz, CHCHCHaHb),
5.03 (1 H, ddd, 19 Hz, 3 Hz, 3 Hz, CHCHCHaHb), 5.81 (1 H,
ddd, 8 Hz, 3 Hz, 2 Hz, CHCHCHaHb), 6.40 (2 H, d, 2 Hz, Ph),
6.55 (1 H, t, 2 Hz, Ph) ppm. 13C NMR (CD3CN, 75 MHz):
δ 38.6, 56.3, 81.3, 95.0, 101.6, 106.4, 134.5, 162.0, 170.4,
176.4 ppm. IR (solid state): ν 3007.6, 2975.0, 1787.9, 1710.2,
4-exo-t-Butyl-7-methyl-4-phenyl-2,3,7-triazabicyclo[3.3.0]oct-2-
ene-6,8-dione 14a. White solid. H NMR (CDCl3, 300 MHz):
1
δ 1.04 (9 H, s, 3 × CH3), 2.56 (3 H, s, NCH3), 3.39 (1 H, d,
8 Hz, CHCH), 5.86 (1 H, d, 8 Hz, CHCH), 7.24 (3 H, s, Ph),
7.49 (2 H, s, Ph) ppm. 13C NMR (CDCl3, 75 MHz): δ 24.8,
26.3, 39.6, 44.6, 95.3, 108.7, 127.3, 128.0, 136.1, 169.0,
173.5 ppm. IR (solid state): ν 3053.4, 2956.5, 1787.9, 1699.3,
1607.8, 1593.7, 1206.9, 1187.2, 1157.6, 1060.1 cm−1
.
1433.7, 1373.6, 1284.7, 1130.5, 961.6, 708.7 cm−1
.
General procedure for the synthesis of 7-alkyl-4,4-diphenyl-
2,3,7-triazabicyclo[3.3.0]oct-2-ene-6,8-dione 13. Ethereal diphenyl-
diazomethane (5 equiv.) was added to N-alkyl maleimide 11
(0.45 mmol) dissolved in 10–25 mL ether and the solution was
stirred overnight. To the N-methyl and N-benzyl reactions,
hexane was added and the mixture allowed to stand for 1 h. The
white solid was filtered and washed with ether until the diphe-
nyldiazomethane was washed away. The product was used
without further purification.
7-Benzyl-4-exo-t-butyl-4-phenyl-2,3,7-triazabicyclo[3.3.0]oct-2-
ene-6,8-dione 14c. White solid. H NMR (CDCl3, 300 MHz):
1
δ 1.05 (9 H, s, 3 × CH3), 3.38 (1 H, d, 8 Hz, CHCH), 4.22 (1 H,
d, 14 Hz, CHaHb), 4.39 (1 H, d, 14 Hz, CHaHb), 5.86 (1 H, d,
8 Hz, CHCH), 6.70 (2 H, d, 7 Hz, Ph), 7.03–7.15 (3 H, m, Ph),
7.23 (3 H, s, Ph), 7.49 (2 H, s, Ph) ppm. 13C NMR (CDCl3,
75 MHz): δ 26.3, 39.7, 42.4, 44.5, 95.5, 109.1, 127.5, 127.7,
128.0, 128.0, 128.6, 134.7, 136.2, 168.5, 173.3 ppm.
4-exo-t-Butyl-4,7-diphenyl-2,3,7-triazabicyclo[3.3.0]oct-2-ene-
6,8-dione 14d. White solid. 1H NMR (CDCl3, 300 MHz): δ 1.45
(9 H, s, 3 × CH3), 3.50 (1 H, d, 8 Hz, CHCH), 6.10 (1 H, d,
8 Hz, CHCH), 6.48–6.51 (2 H, m, Ph), 7.22–7.27 (3 H, m, Ph),
7.31 (3 H, s, Ph), 7.52 (2 H, s, Ph) ppm. 13C NMR (CDCl3,
75 MHz): δ 26.5, 39.3, 45.2, 95.0, 109.2, 126.2, 128.1, 128.8,
129.1, 130.9, 136.7, 167.8, 172.9 ppm. IR (solid state):
ν 3063.7, 2963.0, 1779.6, 1716.3, 1596.6, 1493.4, 1377.3,
7-Methyl-4,4-diphenyl-2,3,7-triazabicyclo[3.3.0]oct-2-ene-6,8-
dione 13a. White solid. 13C CPMAS (MAS 10 MHz): δ 25.2,
44.3, 95.2, 106.3, 124.7, 127.6, 128.7, 130.0, 130.5, 131.2,
131.8, 132.6, 140.6, 141.9, 168.8, 171.8 ppm. IR (solid state):
ν 3056.6, 2971.8, 1787.5, 1701.2, 1492.7, 1426.0, 1375.7,
1279.3, 748.9, 697.9 cm−1
.
7-Benzyl-4,4-diphenyl-2,3,7-triazabicyclo[3.3.0]oct-2-ene-6,8-
dione 13c. White solid. 13C CPMAS (MAS 10 MHz): δ 43.1,
44.6, 97.1, 106.4, 126.0, 128.0, 128.6, 129.7, 131.2, 132.1,
136.5, 140.3, 143.0, 170.5, 174.0 ppm. IR (solid state):
ν 3053.5, 3000.1, 1784.2, 1709.4, 1496.3, 1391.9, 1351.4,
1190.1, 1173.0, 730.4 cm−1
.
7-(4-Biphenyl)-4-exo-t-butyl-4-phenyl-2,3,7-triazabicyclo[3.3.0]-
oct-2-ene-6,8-dione 14e. White solid. 1H NMR (CDCl3,
300 MHz): δ 1.17 (9 H, s, 3 × CH3), 3.53 (1 H, d, 8 Hz,
CHCH), 6.13 (1 H, d, 8 Hz, CHCH), 6.57 (dd, 7 Hz, 2 Hz, 2H),
7.33–7.57 (12 H, m, Ar) ppm. 13C NMR (CDCl3, 75 MHz):
δ 26.7, 39.5, 45.3, 95.0, 109.6, 126.5, 127.3, 127.9, 128.0,
128.3, 128.9, 129.9, 136.7, 140.1, 142.0, 167.8, 173.0 ppm. IR
(solid state): ν 3057.3, 2952.2, 1716.0, 1519.0, 1373.6, 1185.0,
1170.7, 742.3, 695.5 cm−1
.
4,4,7-Triphenyl-2,3,7-triazabicyclo[3.3.0]oct-2-ene-6,8-dione
13d. White solid. 13C CPMAS (MAS 10 MHz): δ 44.8, 95.4,
106.1, 125.6, 128.4, 130.0, 131.9, 140.9, 169.5, 172.1 ppm.
IR (solid state): ν 3057.6, 2962.8, 1718.2, 1595.1, 1494.0,
759.7 cm−1
.
1379.9, 1179.5, 736.5, 690.0 cm−1
.
4-exo-t-Butyl-7-(3,5-dimethoxyphenyl)-4-phenyl-2,3,7-triazabi-
cyclo[3.3.0]oct-2-ene-6,8-dione 14f. White solid. 1H NMR
(CDCl3, 300 MHz): δ 1.15 (9 H, s, 3 × CH3), 3.48 (1 H, d,
8 Hz, CHCH), 3.61 (6 H, s, 2 × OCH3), 5.58 (2 H, d, 2 Hz, Ph),
6.10 (2 H, d, 8 Hz, CHCH), 6.34 (1 H, t, 2 Hz, Ph), 7.30 (4H, s,
Ph), 7.58 (1 H, s, Ph) ppm. 13C NMR (CDCl3, 75 MHz): δ 26.6,
7-(4-Biphenyl)-4,4-diphenyl-2,3,7-triazabicyclo[3.3.0]oct-2-ene-
6,8-dione 13e. White solid. 13C CPMAS (MAS 10 MHz):
δ 45.4, 95.0, 105.9, 128.7, 141.2, 142.4, 167.0, 170.5 ppm. IR
(solid state): ν 3058.3, 2961.2, 1784.7, 1717.1, 1518.0, 1486.3,
1380.7, 1195.5, 1175.9, 754.5, 697.6 cm−1
.
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View Article Online
39.4, 45.3, 55.6, 94.9, 101.8, 104.5, 109.4, 128.2, 132.3, 136.9,
75 MHz): δ 27.5, 30.5, 35.0, 54.9, 126.6, 128.2, 128.4, 128.6,
129.0, 131.3, 131.8, 134.8, 173.9 ppm. IR (solid state):
ν 3079.1, 2975.2, 1770.5, 1701.7, 1519.6, 1486.9, 1365.1,
161.0, 167.5, 172.8 ppm. IR (solid state): ν 3003.7, 2970.0,
1713.5, 1610.8, 1457.7, 1205.9, 1181.5, 1157.1 cm−1
.
1177.4, 763.1, 689.3 cm−1
.
General procedure for the solution photolysis
3-(4-Biphenyl)-6-exo-t-butyl-6-phenyl-3-azabicyclo[3.1.0]hexane-
2,4-dione 19e. 1H NMR (CDCl3, 300 MHz): δ 1.00 (9 H, s,
3 × CH3), 3.05 (2 H, s, 2 × CH), 6.30 (2 H, d, 9 Hz, Ar),
7.29–7.47 (12 H, m, Ar) ppm. 13C NMR (CDCl3, 75 MHz):
δ 27.6, 30.6, 35.1, 55.0, 126.8, 127.3, 127.7, 127.9, 128.3,
128.4, 128.9, 130.4, 131.9, 134.8, 140.4, 141.6, 173.9 ppm. IR
(solid state): ν 3074.2, 2960.4, 1772.5, 1700.9, 1610.8, 1596.0,
The pyrazolines (4–6 mg) were dissolved in 3 mL acetonitrile
and the solution was deoxygenated with argon. The solutions
were photolyzed with a quartz-filtered medium-pressure Hg
1
Hanovia lamp. The reaction was monitored by H NMR spec-
troscopy, by taking samples as a function of time throughout the
photolysis. Each time a sample was removed, the solution was
deoxygenated before the photolysis was continued.
1475.0, 1336.9, 1203.1, 1179.7, 1154.6, 705.3 cm−1
.
6-exo-t-Butyl-3-(3,5-dimethoxyphenyl)-6-phenyl-3-azabicyclo-
[3.1.0]hexane-2,4-dione 19f. 1H NMR (CDCl3, 300 MHz):
δ 0.97 (9 H, s, 3 × CH3), 3.01 (2 H, s, 2 × CH), 3.59 (6 H, s, 2 ×
OCH3), 5.32 (2 H, d, 2 Hz, Ph), 6.30 (1 H, t, 2 Hz, Ph),
7.32–7.38 (5 H, m, Ph) ppm. 13C NMR (CDCl3, 75 MHz):
δ 27.5, 30.5, 35.0, 54.9, 55.6, 101.8, 104.8, 128.3, 132.0,
132.7, 134.9, 160.9, 173.7 ppm. IR (solid state): ν 3063.9,
2970.6, 1773.3, 1704.9, 1598.8, 1493.4, 1378.4, 1181.6,
General procedure for the solid-state photolysis
The solid 1-pyrazoline was spread over glass microscope plates
and the solid was photolyzed directly with a quartz-filtered
medium-pressure Hg Hanovia lamp. The reaction was monitored
by 1H solution NMR or 13C CP/MAS solid-state NMR
spectroscopy.
697.0 cm−1
.
The spectral data of 14a match literature spectra.19
3-Benzyl-6,6-diphenyl-3-azabicyclo[3.1.0]hexane-2,4-dione
18c. 1H NMR (CDCl3, 300 MHz): δ 3.16 (2 H, s, 2 × CH), 4.07
(2 H, s, CH2), 6.97–7.35 (15 H, m, 3 × Ph) ppm. 13C NMR
(CDCl3, 75 MHz): δ 34.1, 42.0, 50.6, 127.0, 127.5, 127.8,
128.5, 128.6, 128.7, 129.0, 129.2, 129.5, 135.3, 135.7, 141.6,
172.9 ppm. IR (solid state): ν 3064.8, 2952.6, 1762.9, 1689.3,
Acknowledgements
We are grateful to the National Science Foundation for support
through grants CHE-0844455.
1493.5, 1438.1, 1400.9, 1340.6, 693.8 cm−1
.
Notes and references
3,6,6-Triphenyl-3-azabicyclo[3.1.0]hexane-2,4-dione 18d. 1H
NMR (CDCl3, 300 MHz): δ 3.33 (2 H, s, 2 × CH), 6.33–6.36
(2 H, m, Ph), 7.23–7.57 (13 H, m, Ph) ppm. 13C NMR (CDCl3,
75 MHz): δ 34.0, 50.1, 126.6, 127.1, 128.0, 128.6, 128.7, 129.1,
129.1, 129.6, 129.9, 131.2, 136.3, 141.2, 172.3 ppm. IR (solid
state): ν 3063.0, 1770.0, 1703.8, 1598.2, 1495.5, 1375.9,
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1174.6, 689.8 cm−1
.
3-(4-Biphenyl)-6,6-diphenyl-3-azabicyclo[3.1.0]hexane-2,4-dione
18e. 1H NMR (CDCl3, 300 MHz): δ 3.53 (2 H, s, 2 × CH),
6.40–6.43 (2 H, m, Ph), 7.28–7.59 (17 H, m, Ar) ppm. 13C
NMR (CDCl3, 75 MHz): δ 34.1, 50.2, 126.8, 127.1, 127.3,
127.7, 127.9, 128.1, 128.7, 128.9, 129.2, 129.6, 129.9, 130.3,
136.4, 140.4, 141.2, 141.8, 172.4 ppm. IR (solid state):
ν 3058.8, 1774.0, 1707.5, 1598.2, 1494.1, 1387.3, 1182.1,
694.8 cm−1
.
6-exo-t-Butyl-3-methyl-6-phenyl-3-azabicyclo[3.1.0]hexane-2,4-
dione 19a. 1H NMR (CDCl3, 300 MHz): δ 0.90 (9 H, s, 3 ×
CH3), 2.14 (3 H, s, NCH3), 2.83 (2 H, s, 2 × CH), 7.16–7.26
(5 H, m, Ph) ppm. 13C NMR (CDCl3, 75 MHz): δ 23.5, 27.5,
30.3, 34.7, 55.3, 127.9, 127.9, 131.3, 134.7, 174.8 ppm. IR
(solid state): ν 3086.0, 2972.2, 1769.0, 1691.7, 1430.4, 1373.3,
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.
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19d. 1H NMR (CDCl3, 300 MHz): δ 0.98 (9 H, s, 3 × CH3),
3.02 (2 H, s, 2 × CH), 6.20–6.24 (2 H, m, Ph), 7.16–7.19 (3 H,
m, Ph), 7.34–7.36 (5 H, m, Ph) ppm. 13C NMR (CDCl3,
1936 | Photochem. Photobiol. Sci., 2012, 11, 1929–1937
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21 The 13C CP/MAS spectra were acquired at a 13C frequency of 75 MHz
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sition time of 66 ms, and a recycle delay of greater than five times the
spin-lattice relaxation time of the protons. The sample was spun at a
MAS rate of 10 MHz.
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12 Although reported as photolyses of crystalline samples of exo- and endo-
1, both compounds are oils at room temperature and the crystalline
samples were prepared by crystallizing the samples at −80 °C. However,
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may in fact be supercooled oils.
5
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