◦
ESI). At 25 C a rate constant for the VHF ring-closure of 4.71
¥ 10-5 s-1 was obtained (half-life of 245 min). From an Arrhenius
plot (see ESI), an activation energy of 93.1 ( 0.7) kJ mol-1 and a
preexponential factor of 9.8 ¥ 1011 s-1 were determined. Yet, each
VHF likely has a different rate constant for forming either one of
the two possible DHAs at any specific temperature. What we have
estimated is a net rate constant of ring-closure, assumed identical
for each VHF isomer, but which for each VHF is the sum of
two unknown rate constants. As the temperature variation of this
net rate constant satisfies an Arrhenius plot, the two individual
rate constants must differ in their preexponential factors only (the
sum of which is reported above), while their activation energy
terms must be identical. A similar data analysis was previously
performed for the kinetics of formation of 6/7-substituted DHAs
by ring-closure of corresponding isomeric VHFs, but here the data
satisfied a single exponential decay during the entire time span.4–6
In conclusion, we have developed a new procedure for function-
alizing dihydroazulenes in the seven-membered ring. The lack of
regioselectivity renders purification tedious and is a major draw-
back of the protocol, but, nevertheless, it has allowed isolation of
the first DHA that incorporates a phenyl substituent at position
5. Light-induced ring-opening followed by ring-closure at room
temperature provided a mixture of 5- and 8-phenylsubstituted
DHAs. The 8-phenyl-substituted DHA is, however, equilibrating
in the dark to the more stable 5-phenyl-substituted one. This is
the first example of a thermally induced ring-opening of the DHA
system.
Fig. 4 VHF isomers formed upon ring-opening of DHA 3.
Fig. 5 Conversion of E/Z-VHFs 16 into DHAs 3 and 11 followed by
1H-NMR (CD3CN, 25 ◦C). Assignment of H-7 on 11 was done on the
basis of coupling constants.
E- and Z-VHF isomers remained constant during their decay (at
least in the beginning while it is more difficult to judge after some
time where the signals have decreased in intensity), there is a steady
build-up of DHA 3 relative to DHA 11 in time. Moreover, we find
that after ca. 4 days at room temperature in the dark, DHA 11
is almost fully converted to DHA 3 (see ESI). Thus, altogether
the experiments show that not only are the VHFs converted to
DHAs but also that DHA 11 is thermally converted to DHA 3,
most likely via a VHF intermediate. Calculations at the B3LYP/6-
311++G(2d,p)//B3LYP/6-31+G(d) density functional theory
level using the Gaussian 03 program package9 suggest that DHA
3 is more stable than 11 by 6.7 kcal mol-1. The thermally assisted
ring-opening of 11 to a VHF that subsequently ring-closes to form
3 is also in accordance to the absence of this isomer in the original
product mixture, which was isolated after heating to 80 ◦C (albeit
in toluene rather than MeCN, vide supra). Subjecting an ice-cooled
mixture of the DHAs 3 and 11 (in favor of 3) to irradiation for 1
h from a 365 nm UV lamp revealed complete ring-opening of 3 as
Acknowledgements
The Danish Research Council for Independent Research | Natural
Sciences is gratefully acknowledged for financial support. Dr
Christian R. Parker and Mr Christian G. Tortzen are gratefully
acknowledged for helpful discussions and help with experiments.
Notes and references
‡ 1,1-Dicyano-2,5-diphenyl-1,8a-dihydroazulene (3): A crude mixture of
the three regioisomers 7, 8, and 9 (1.63 g, 4.87 mmol) was dissolved
in CH2ClCH2Cl (10 mL). Then tritylium tetrafluoroborate (1.63 g, 4.95
mmol) dissolved in CH2ClCH2Cl was added under an argon atmosphere.
The mixture was heated to 80 ◦C, by which it turned dark red in color.
Toluene (110 mL) was added and the solution was cooled on an ice
bath for 1.5 h. Then Et3N (0.52 g, 5.15 mmol) was added and the
solution was cooled for 10 min. Stirring at 80 ◦C for 1 h followed by
concentration in vacuo yielded a mixture of DHAs (and by-products). By
repeated column chromatography (SiO2, 1. column: EtOAc/heptane 1 : 9;
2. column: CH2Cl2/heptane 2 : 1), it was pos◦sible to isolate 3 (195 mg,
1
judged from H-NMR spectroscopy (see ESI), while 11 was not
1
12%) as a fine, yellow powder. M.p. 128–129 C. H-NMR (CDCl3, 300
fully converted. Thus, it seems that 3 is more light-sensitive than
11, although the two compounds may exhibit slightly different
molar absorptivities at the wavelength of irradiation.
MHz): d 7.77 (dd, J 8.2, 1.5 Hz, 2H), 7.53–7.32 (m, 8H), 6.95 (s, 1H), 6.79
(d, J 6.5 Hz, 1H), 6.58 (s, 1H), 6.41 (ddd, J 10.1, 6.5, 2.0 Hz, 1H), 5.89
(dd, J 10.1, 3.6 Hz, 1H), 3.88 (dt, J 3.6, 2.0 Hz, 1H); 13C-NMR (CDCl3,
75 MHz): d 143.5, 142.1, 141.5, 140.8, 132.4, 130.6, 130.3, 129.4, 128.8,
128.3, 128.3, 127.8, 127.1, 126.5, 122.2, 119.9, 115.3, 112.9, 50.9, 45.3.
The thermal back-reaction of the E/Z-mixture of 16 was also
studied by UV-Vis absorption spectroscopy in MeCN. The decay
in the absorbance at 488 nm was followed at different temperatures
(see ESI). A sum of two exponential functions was required in
order to fit the data, which is in accordance to the fact that the
thermally induced ring-opening of DHA 11 came into play in time.
A single exponential function can, however, be used to fit the data
in the beginning of the VHF to DHA conversion, before DHA 11
has formed in substantial amount. From such single-exponential
fits, rate constants at different temperatures were obtained (see
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6500 | Org. Biomol. Chem., 2011, 9, 6498–6501
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