Photoinduced 1,3-proton shift in methyldithiepines as a potential way of modulating hyperpolarizabilities

Full text of DOI:10.1021/jo005707i

1894
J . Org. Chem. 2001, 66, 1894-1899
Notes
hyperpolarizability γ for 2 and how it is affected by its
rearrangement into 3.
P h otoin d u ced 1,3-P r oton Sh ift in
Meth yld ith iep in es a s a P oten tia l Wa y of
Mod u la tin g Hyp er p ola r iza bilities
Resu lts a n d Discu ssion
Yongqin Wan, Alexei Kurchan, and Andrei Kutateladze*
We have found that upon irradiation in benzene
containing small amounts of hydrochloric acid, dithi-
epines 2a -d undergo 1,3-hydrogen migration leading to
the desired conjugation disruption. The exo-methylenic
dithiepanes 3a -d are kinetic products and in the ground
state they slowly rearrange back into the starting mate-
rial. The dark back-reaction is accelerated in polar
solvents.
Department of Chemistry and Biochemistry, University of
Denver, Denver, Colorado 80208
akutatel@du.edu
Received October 30, 2000
Reversible disruption of conjugation is a useful tech-
nique for affecting electronic properties of organic com-
pounds. One can readily envision, for instance, a formal
scheme involving a 1,3-H shift in a 1,2-propenylidene
fragment connecting the donor (D) and acceptor (A) that
is expected to exert a dramatic effect on properties such
as UV-vis absorption, dipole moment, polarizability, and
hyperpolarizability. Modulating the latter is a challeng-
Photolyses were carried out in degassed benzene
solutions with a medium-pressure mercury lamp utilizing
a Pyrex filter. Only dithiepines bearing an electron-
withdrawing group (EWG) in the aromatic ring were
reactive. Phenyl- or p-methoxyphenyl-substituted dithi-
epines 2e,f degraded under these irradiation conditions.
Other strong acids such as toluenesulfonic and trifluo-
roacetic also induced the rearrangement of 2, whereas
weaker acids, such as acetic, did not produce 3. In
addition, irradiation in benzene in the presence of a small
amount of methanol with no acid added did not induce
the 1,3-proton shift either.
ing problem, which may have far reaching implications
for applied science. The known approaches vary from
ultrafast optical modulation of quadratic nonlinearity
from Ru(bipy)2 complex in Langmuir-Blodgett assem-
blies1 to pH control of NLO properties in hemicyanines
and 4-amino-4′-nitrostilbenes.2
We have been exploring possibilities to use photoin-
duced proton shifts in allylic systems for altering elec-
tronic characteristics of molecules. Intramolecular proton
transfer is widely used in tautomeric photochromes, and
furthermore, its utilization for modulating NLO suscep-
tibilities is certainly not unprecedented in the literature.3
Our specific approach to this problem is based on a proton
shift in the all-carbon allylic moiety of 2-methyl-3-aryl-
6,7-dihydro-5H-[1,4]dithiepines (2), which we prepare
from 2-methyl-1,3-dithiane and substituted benzalde-
hydes as follows:4
To gain further experimental insight into the mecha-
nism we carried out the irradiation of 2a in benzene
1
in the presence of a small amount of DCl/D2O. The H
NMR spectrum of the reaction mixture showed con-
siderable decrease (more than 50%) in the integration
value of the benzylic proton in 3a . We also synthesized
a CD3 derivative of 2a (2a -d 3) and irradiated it in
benzene in the presence of a small amount of hydro-
chloric acid. Only the benzylic peak grew in the pro-
ton NMR of reaction mixture. GC-MS corroborated
these observations. The molecular ion peak for 2a is 247.
After irradiation in the presence of DCl, this value
increased to 248 due to one deuterium atom incorpora-
tion. Likewise, the molecular ion peak for the deuterated
(3) (a) Zhang, Y.; Lu, Z.-H. Mater. Chem. Phys. 2000, 63, 188. (b)
Shiozaki, H.; Matsuoka, M. THEOCHEM 1998, 427 253. (c) Evans, C.
C.; Bagieu-Beucher, M.; Masse, R.; Nicoud, J .-F. Chem. Mater. 1998,
10, 847. (d) Serrano, A.; Canuto, S. Int. J . Quantum Chem. 1998, 70,
745. (e) Shang, X.; Tang, G.; Zhang, G.; Liu, Y.; Chen, W.; Yang, B.;
Zhang, X. J . Opt. Soc. Am. B 1998, 15, 854. (f) Houbrechts, S.; Clays,
K.; Persoons, A.; Pikramenou, Z.; Lehn, J .-M. Chem. Phys. Lett. 1996,
258, 485. (g) Neykov, G.; Enchev, V.; Monev, V.; Kanev, I. Mol. Eng.
1995, 5, 347. (h) Albert, I. D. L.; Morley, J . O.; Pugh, D. J . Phys. Chem.
1995, 99, 8024. (i) Hoefer, T.; Kruck, P.; Kaiser, W. Chem. Phys. Lett.
1994, 224, 411.
We now present an experimental mechanistic study of
this novel 1,3-proton migration in a series of dithiepines
2, augmented with ab initio evaluations of the second
(1) Sakaguchi, H.; Nagamura, T.; Penner, T. L.; Whitten, D. G. Thin
Solid Films 1994, 244, 947.
(2) Shen, Y. R. In Molecular nonlinear optics; Zyss, J ., Ed.: Academic
Press: New York, 1994; p 113 and references therein.
(4) Wan, Y.; Barnhurst, L. A.; Kutateladze, A. G. Org. Lett. 1999,
1, 937.
10.1021/jo005707i CCC: $20.00 © 2001 American Chemical Society
Published on Web 02/01/2001

Notes
J . Org. Chem., Vol. 66, No. 5, 2001 1895
2a -d 3 is 250, and after irradiation the product’s molec-
ular ion was found to be 249 due to the one deuterium
loss.
Running the photolysis under oxygen saturation condi-
tions did not inhibit the 1,3-shift in 2a ,5 ruling out the
involvement of a triplet state.
F igu r e 1. Deprotonated 2a : ground-state b3lyp/6-31g* ge-
ometry (left) and the NBO charges breakdown for the twisted
fragments (right).
Our experimental results indicate that the observed
hydrogen migration is a nonconcerted proton transfer
initiated in the excited singlet state of 2. There are two
possible mechanisms for such a proton migration, differ-
ing only in the order of C-H bond breaking/forming: (i)
deprotonation of the methyl group in the excited state
followed by reprotonation at the benzylic position or (ii)
protonation of the benzylic position followed by deproto-
nation of the methyl.
F igu r e 2. A Brønsted-type plot of the relative quantum
efficiencies of the 1,3-shift in 2 as a function of pKa.
enhanced flexibility of the seven-member dithiepine ring,
excited 2 may exist either in the form of a “conventional”
TICT state (A) with the aromatic ring twisted out of
conjugation, or the alternative (B), with a twisted S-C-
C-S fragment. The state B, an ionic ethylenic state, is
a good candidate for the benzylic protonation (path ii).
Both states require an electron-withdrawing substitutent
in the aromatic ring.
The first mechanism is supported by the well-known
fact that excited states are commonly much more acidic
than their respective ground states. After deprotonation,
the ground-state anion is reprotonated at the benzylic
position. To better understand the regiochemistry of such
kinetic protonations, we optimized the geometry of the
anion derived from 2a at the b3lyp/6-31g* level and
analyzed the charge distribution utilizing Weinhold’s
natural bond orbital analysis.6 The S-C-C-S fragment
(Figure 1) of the anion is twisted heavily, with the two
moietiessvinyl sulfide and aryl-CHsbeing almost or-
thogonal (CH2-C-C-Ar dihedral angle is 90.7°). The
cumulative natural charge of the vinyl sulfide fragment
was calculated to be -0.05, whereas the S-CH-Ar
moiety amassed the bulk of the negative charge, -0.73.
It was therefore conceivable that the charge-controlled
kinetic protonation of such anion would lead to 3a , not
back to 2a .
Due to the size of the system, we were unable to
computationally obtain the geometry and the charge
distribution in the singlet excited state of 2a at an
adequate level of theory. However, we believe that the
lack of reactivity in the absence of stronger acids supports
path ii. If the path i were operational, with excited 2a
losing one of its methyl protons first, the generated
ground-state anion should be able to deprotonate metha-
nol or acetic acid; a very liberal lower estimate for pKa
of the benzylic proton in 3a based on several analogous
systems compiled in Bordwell’s review7 is 20.
As mentioned above, we observed no reaction in the
presence of acetic acid (pKa ) 4.76). To cover a wider
acidity range, we irradiated 2a in the presence of formic
(pKa ) 3.75) and chloroacetic (pKa ) 2.85) acids. In both
cases, very small amounts of 3a were observed after 2 h
of irradiation. Although the acidity constants we used
are reported for aqueous solutions, we found it informa-
tive to plot the logarithm of relative quantum efficiency
of the rearrangement as a function of pKa (a quasi-
Brønsted plot). Figure 2 shows a relatively good fit with
correlation coefficient exceeding 0.9 and the Brønsted’s
R ) 0.29, implicating general acid catalysis.
The second mechanism, protonation-deprotonation,
would necessitate accumulation of electronic density at
the benzylic position of the excited 2, implicating a
charge-separated excited state. We note that due to the
(5) although an increased amount of minor side products were
observed, most certainly due to direct oxidation of sulfur.
(6) Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. Rev. 1988, 88,
899.
(7) Bordwell, F. G. Acc. Chem. Res. 1988, 21, 456.

1896 J . Org. Chem., Vol. 66, No. 5, 2001
Notes
F igu r e 3. Comparison of the UV spectra for 2a and 3a in
benzene.
F igu r e 5. DFT energy diagram of 2•+ f TS f 3•+ transfor-
mation as a concerted 1,3-hydrogen shift. The relative energies
are zpe-corrected: kcal/mol (kJ /mol).
We first considered the possibility that in acid-free
carbon tetrachloride the mechanism may be different,
e.g., involving a photoinduced single electron transfer,
by analogy with our previous observations on CCl4
photooxidation of aryldithiepines bearing electron donors
in the aromatic ring.4 It was then very tempting to
explain the efficient 2•+ f 3•+ transformation in terms
of a concerted 1,3-shift,8 because of an apparent driving
force, i.e., the necessity to shut off the conjugation of the
electron-withdrawing aromatic ring from the sulfur-
centered cation-radical.
To assess the feasibility of such a concerted 1,3-
hydrogen migration in 2a •+, we carried out DFT compu-
tations at the b3lyp/6-31g* level of theory on the cation-
radical of the starting material (2•+), the cation-radical
of the product (3••), and the transition state. The geom-
etries were optimized to stationary points as verified by
vibrational analysis. Structures 2•+ and 3•+ showed no
imaginary frequencies whereas the transition structure
had one imaginary mode corresponding to the reaction
coordinate. Zpe-corrected relative energies are presented
in Figure 5.
F igu r e 4. HCl concentration dependence of the rate of the
reverse (dark) reaction 3a f 2a in acetonitrile.
There is no photoequilibration between 2a and 3a ,
possibly owing to considerable difference in their UV
absorbance. While 2a has a strong maximum at 350 nm,
3a has only a weak absorbance above the Pyrex cutoff
(Figure 3). The reverse reaction, which is also catalyzed
by acids, occurs in the ground state. Most certainly it is
a thermodynamically driven protonation-deprotonation.
We optimized the geometries of 2a and 3a in the ground
state at the b3lyp/6-31g* level and found that the zpe-
corrected relative energy was about 7.5 kcal/mol (31.4 kJ /
mol) favoring the starting 2a .
Irradiation of 2a in acetonitrile in the presence of HCl
produces 3a , which reverses to 2a much faster than in
nonpolar benzene. By photobleaching the UV absorbance
at 350 nm and monitoring its recovery in the dark, we
measured the rates of the reverse reaction. Figure 4
shows the dependence of the pseudo-first-order rate
First, our computations showed that 3a •+ is actually
higher in energy than 2a •+ by 28.1 kcal/mol (117.6 kJ /
mol). Notice that the conjugation interruption in 3a •+
shuts off not only the electron-withdrawing aromatic ring
but also the second sulfur atom, thus contributing to the
overall destabilization of the cation radical. Most impor-
tantly, the activation barrier, 69.4 kcal/mol (290.4 kJ /
mol), is prohibitively high for a concerted reaction to
occur. We therefore believe that the reaction follows the
same protonation-deprotonation mechanism with a trace
amount of HCl either present in CCl4, or generated
during the photolysis. The maximum conversion in “acid-
free” carbon tetrachloride is limited to about 50%, after
which considerable degradation of products was observed.
The reaction in benzene can be driven to near 100%
conversion with very little degradation, allowing repeti-
tion of the cycle.
constant on the concentration of HCl: krev ) 0.0012CHCl
.
The intercept (0.0007) is very close to zero, indicating that
a spontaneous (not catalyzed) back proton migration is
virtually nonexistent. In the presence of 1 mM HCl
(acetonitrile), τ1/2 is approximately 15 min. The proton
NMR spectrum obtained after a full bleach-recovery cycle
showed that only starting 2a is present in the reaction
mixture. At higher acid concentrations, the rate of the
dark reaction was higher, but the absorbance never fully
recovered to the starting value. We believe that this
irreversible bleaching is due to hydrolysis of the dithi-
epane ring at higher acid concentrations.
The photoinduced 1,3-proton migration in substituted
dithiepines 2 may potentially be utilized for modulating
hyperpolarizabilities. We addressed this issue theoreti-
Other nonpolar solvents, such as carbon tetrachloride,
can also be successfully utilized in place of benzene to
carry out this photoinduced 1,3-migration. As in benzene,
the reverse reaction is much slower than in polar aceto-
nitrile. An unexpected finding was that this rearrange-
ment occurs in CCl4 even with no acids added.
(8) Concerted 1,3-hydrogen migrations in cation radicals were
reported previously. See, for example: Nguen, M. T.; Landuyt, L.
Vanquickenborne L. G. Chem. Phys. Lett. 1991, 182, 225 and references
therein.

Notes
J . Org. Chem., Vol. 66, No. 5, 2001 1897
F igu r e 6. Second hyperpolarizabilities in the “on” (2a ,b,d ) and “off” (3a ,b,d ) states as compared with that of nitroaniline. γzzzz
values for compounds 2b and 3b are computed for both syn and anti (with respect to the methyl) conformations of 3-cyanophenyl
group; the same applies to the formyl’s oxygen in compounds 2d and 3d .
performed on silica gel, 70-230 mesh ASTM, using ethyl ace-
tate-hexane mixtures as eluent. HP 6890 with MSD detector
was used to analyze the reaction mixtures. The Pyrex-filtered
output of a medium-pressure Hanovia lamp was utilized as the
UV source.
cally by carrying out the finite field computations at rhf
level of theory utilizing 3-21g* basis set and comparing
our calculated values for second hyperpolarizability with
that calculated by Dupuis for one of the organic NLO
standards, p-nitroaniline.9 As we expected, the value for
the axial component of the second hyperpolarizability γ,
Com p u ta tion a l Meth od s. Ab initio geometry optimizations
were carried out with the Gaussian 98 package10 using density
functional theory (DFT) at the b3lyp/6-31g* level (the Becke
three-parameter hybrid functional combined with Lee, Yang, and
Parr correlation functional11). The stationary points were char-
acterized with vibrational analysis at the same level of theory.
Zero-point energies were scaled by 0.9804.12 The reported values
for the second hyperpolarizability were obtained utilizing the
finite field approach (field increments -0.002, -0.001, 0.001,
and 0.002) as implemented in GAMESS ab initio package.13
Syn th esis of Deu ter a ted 2-Meth yl-d 3-[1,3]d ith ia n e. A
solution of 1,3-dithiane (4.23 g, 35.2 mmol) in 100 mL of freshly
distilled THF was cooled to -25 °C under nitrogen. Then
n-butyllithium (1.6M solution in hexanes, 42.3 mmol, 26.0 mL)
was added dropwise upon stirring. The mixture was stirred for
2 h at -25 °C before the temperature was lowered to -78 °C.
Iodomethane-d3 (5.00 g, 35.2 mmol) was added dropwise into
this solution of anion upon stirring. After 1 h at this temperature
and then 2 h at -25 °C, the reaction was quenched with
saturated solution of ammonium chloride, extracted twice with
50 mL of diethyl ether, and dried over magnesium sulfate. The
solvent was then removed and the residue was distilled at
reduced pressure 67-68 °C/4 mmHg to give 3.62 g yellowish oil,
75% yield: 1H NMR (CDCl3, 400 MHz) δ 4.11 (s, 1H), 2.95-2.77
(m, 4H), 2.15-2.05 (m, 1H), 1.88-1.76 (m, 1H).
γzzzz calculated for 2a ,b,d was impressively high, ranging
from 2 × 104 to 3 × 104 atomic units (Figure 6). This value
decreased dramatically in the “off” states 3, because of
disrupted conjugation between the donor, dithiepine ring,
and the aryl acceptor. As a comparison, the value of γzzzz
calculated by Dupuis for p-nitroaniline is 1.55 × 104. The
second hyperpolarizability for 2b (largest computed in
our series) exceeded it by a factor of 2. At the same time,
it drops by an order of magnitude in the “off” state (3b),
amounting only to about 20% of the nitroaniline’s value.
Compounds 2a ,d showed similar large changes in γzzzz
,
see Figure 6.
To summarize, we have developed a novel methyldithi-
epine-based photochromic system, capable of a reversible
photoinduced 1,3-proton shift, which effectively disrupts
the conjugation between the donor and the acceptor
moieties, offering among other things a potential way of
modulating hyperpolarizabilities. Our mechanistic ratio-
nale includes protonation of the ethylenic moiety in the
excited dithiepine 2 followed by the ground-state depro-
tonation of the methyl leading to 3. The reverse dark
reaction, which takes place in the ground state, is also a
protonation-deprotonation process. It is accelerated by
solvent polarity and acidity of the media.
Gen er a l P r oced u r e for th e Meth yld ith ia n e-Ald eh yd e
Ad d u ct P r ep a r a tion . A solution of 2-methyl-1,3-dithiane (1.04
(10) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb M. A.; Cheeseman, J . R.; Zacharevski, V. G.; Montgomery, J . A.;
Stratmann, R. E.; Burant, J . C.; Dapprich, S.; Millam, J . M.; Daniels,
A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J .; Barone, V.;
Cossi, M.; Cammi, R.; Mennucci, G.; Pomelli, C.; Adamo, C.; Clifford,
S.; Ochterski, J .; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma,
K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J . B.;
Cioslowski, J .; Ortiz, J . V.; Baboul, A. G.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.;
Fox, D. J .; keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Gonzalez, C.; Head-Gordon, M.; Replogle, E. C.; Pople, J . A. Gaussian
98, revision A.6.
(11) (a) Becke, A. D. Phys. Rev. A. 1988, 38, 3098. (b) Lee, C.; Yang,
W.; Parr. R. G. Phys. Rev. B. 1988, 37, 785.
(12) Wong, M. W. Chem. Phys. Lett. 1996, 256, 391.
(13) Schmidt, M. W.; Baldridge, K. K.; Boatz, J . A.; Elbert, S. T.;
Gordon, M. S.; J ensen, J . H.; Koseki, S.; Matsunaga, N.; Nguyen, K.
A.; Su, S. J .; Windus, T. L.; Dupuis, M.; Montgomery, J . A. J . Comput.
Chem. 1993, 14, 1347.
Exp er im en ta l Section
Gen er a l Meth od s. Unless otherwise specified, solvents and
reagents were purchased from commercial suppliers and used
without further purification. THF was refluxed over and distilled
from potassium benzophenone ketyl prior to use. 1H and 13C
NMR spectra were recorded at 25 °C on a Varian Mercury 400
MHz instrument. In CDCl3, TMS was used as an internal stan-
dard; in C6D6, benzene is used as an internal standard. UV-vis
spectra were obtained by using DU Series 600 Spectrophotom-
eter (Beckman Instruments, Inc.). Column chromatography was
(9) Sim, F.; Chin, S.; Dupuis, M.; Rice, J . E. J . Phys. Chem. 1993,
97, 1158.

1898 J . Org. Chem., Vol. 66, No. 5, 2001
Notes
g, 7.76 mmol) in 50 mL of freshly distilled THF was cooled to
-25 °C under nitrogen. Then n-butyllithium (1.6 M solution in
hexanes, 8.5 mmol, 5.3 mL) was added dropwise upon stirring.
The resulting mixture was stirred for 2 h at -25 °C. The solution
of the dithianyl anion was added dropwise to a vigorously stirred
solution of an appropriate aromatic aldehyde14 (7.76 mmol) in
20 mL of THF at -78 °C. The reaction mixture was stirred for
1 h at this temperature and then stored in a freezer at -25 °C
overnight. The subsequent aqueous workup included quenching
the reaction mixture with a saturated solution of ammonium
chloride, extracting twice with 30 mL of diethyl ether, and drying
the combined organic extracts over magnesium sulfate. The
solvent was then removed in a vacuum, and the residue was
purified on a slurry-packed silica gel column, eluted with ethyl
acetate/hexane.
4-[H yd r oxy(2-m et h yl[1,3]d it h ia n -2-yl)m et h yl]b en zon i-
tr ile (1a ): 67%; 1H NMR (CDCl3, 400 MHz) δ 7.63-7.57 (m, 4H),
5.12 (s, 1H), 3.40 (s, 1H), 3.23-3.16 (m, 1H), 3.11-3.04 (m, 1H),
2.77-2.66 (m, 2H), 2.23-2.15 (m, 1H), 1.98-1.85 (m, 1H), 1.210-
(s, 3H); 13C NMR (CDCl3, 100 MHz) δ 142.9, 130.7, 129.1, 118.7,
112.4, 72.6, 53.5, 26.7, 26.0, 24.0, 22.0. Anal. Calcd for C13H15S2-
ON: C, 58.82; H, 5.70. Found: C, 58.42; H, 5.77.
4-[H yd r oxy(2-m et h yl-d 3-[1,3]d it h ia n -2-yl)m et h yl]b en -
zon itr ile (1a -d 3). 2-Methyl-d3-[1,3]dithiane was used instead
of 2-methyl[1,3]dithiane: 57%; 1H NMR (CDCl3, 400 MHz) δ
7.59-7.61(m, 4H), 5.13 (s, 1H), 3.39 (s, 1H), 3.24-3.16 (m, 1H),
3.12-3.03 (m, 1H), 2.78-2.65 (m, 2H), 2.24-2.15 (m, 1H), 1.97-
1.85 (m, 1H); 13C NMR (CDCl3, 100 MHz) δ 142.9, 130.7, 129.1,
118.7, 111.5, 72.6, 53.3, 26.7, 26.0, 24.0.
3-[H yd r oxy(2-m et h yl[1,3]d it h ia n -2-yl)m et h yl]b en zon i-
tr ile (1b): 76%; 1H NMR (CDCl3, 400 MHz) δ 7.79 (s, 1H), 7.74
(d, J ) 7.5 Hz, 1H), 7.59 (d, J ) 7.9 Hz, 1H), 7.42 (t, J ) 8 Hz,
1H) 5.11 (s, 1H), 3.39 (s, 1H), 3.25-3.16 (m, 1H), 3.15-3.05 (m,
1H), 2.80-2.66 (m, 2H), 2.26-2.10 (m, 1H), 1.99-1.86 (m, 1H),
1.20(s, 3H).
4-[H yd r oxy(2-m et h yl[1,3]d it h ia n -2-yl)m et h yl]b en zoic
a cid m et h yl est er (1c): 47%; 1H NMR (CDCl3, 400 MHz) δ
7.976 (d, J ) 8.1 Hz, 2H), 7.55 (d, J ) 8.1 Hz, 2H), 5.13 (s, 1H),
3.90 (s, 3H), 3.38 (s, 1H), 3.24-3.15 (m, 1H), 3.10-3.01 (m, 1H),
2.76-2.64 (m, 2H), 2.21-2.12 (m, 1H), 1.96-1.85 (m, 1H), 1.25
(s, 3H); 13C NMR (CDCl3, 100 MHz) δ 166.6, 142.6, 129.4, 128.4,
128.3, 73.1, 53.7, 52.0, 26.7, 26.0, 24.1, 22.3. Anal. Calcd for
C14H18S2O3: C, 56.35; H, 6.08. Found: C, 56.49; H, 6.15.
(4-Me t h oxyp h e n yl)(2-m e t h yl[1,3]d it h ia n -2-yl)m e t h a -
n ol (1f): 86%; 1H NMR (CDCl3, 400 MHz) δ 7.38 (d, J ) 8.6 Hz,
2H), 6.85 (d, J ) 8.6 Hz, 2H), 5.05 (s, 1H), 3.795 (s, 3H), 3.21 (s,
1H), 3.22-3.13 (m, 1H), 3.10-3.01 (m, 1H), 2.76-2.63 (m, 2H),
2.18-2.09 (m, 1H), 1.96-1.84 (m, 1H), 1.31 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 159.0, 129.3, 112.6, 73.6, 55.2, 54.1, 26.7,
26.0, 24.4, 22.4. Anal. Calcd for C13H18S2O2: C, 57.74; H, 6.71.
Found: C, 57.82; H, 6.76.
Gen er a l P r oced u r e for P r ep a r a tion of th e Dith iep in es
2. Meth od A. A solution of methyldithiane-aldehyde adduct
(1 mmol) and triethylamine (5 mmol) in 20 mL of CCl4 was cooled
to 0 °C, and SOCl2 (1.7 mmol) was added upon stirring. After 2
min, the reaction was quenched with the addition of 10 mL of
aqueous HCl. The organic phase was separated, and the aqueous
layer was extracted with CH2Cl2 (10 mL × 2). The combined
organic phase was dried with MgSO4, concentrated in a vacuum,
and purified on a slurry-packed silica gel column and eluted with
ethyl acetate/hexane. Meth od B. To a refluxed solution of
methyldithiane-carbonyl adduct (1 mmol) in benzene (10 mL)
under nitrogen atmosphere was added TsOH‚H2O (0.1 mmol)
and the mixture was refluxed for 2 h. The reaction mixture was
cooled to room temperature and washed with saturated NaHCO3
(10 mL). The aqueous layer was extracted with benzene (10 mL
× 2). The organic phases were combined, dried with MgSO4, and
concentrated in a vacuum. The residue was purified on a slurry-
packed silica gel column and eluted with ethyl acetate/hexane.
4-(3-Meth yl-6,7-d ih yd r o-5H-[1,4]d ith iep in -2-yl)ben zon i-
tr ile (2a ): method B; 71%; H NMR (CDCl3, 400 Hz) δ 7.59 (d,
1
J ) 7.8 Hz, 2H), 7.38 (d, J ) 7.8 Hz, 2H), 3.56 (t, J ) 5.6 Hz,
2H), 3.52 (t, J ) 5.6 Hz, 2H), 2.14 (quintet, J ) 5.6 Hz, 2H),
1.73 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 146.1, 131.9, 130.5,
129.8, 126.8, 118.6, 110.9, 33.1, 31.4, 29.6, 24.5; MS (EI) m/z
(relative intensity) 247 (M+, 100), 218 (10), 173 (20), 140 (15),
106 (20). Anal. Calcd for C13H13S2N: C, 63.12; H, 5.30. Found:
C, 62.75; H, 5.40.
4-(3-Met h yl-d 3-6,7-d ih yd r o-5H -[1,4]d it h iep in -2-yl)b en -
1
zon itr ile (2a -d 3): method B; 70%; H NMR (CDCl3, 400 Hz) δ
7.59 (d, J ) 8.2 Hz, 2H), 7.38 (d, J ) 8.2 Hz, 2H), 3.56 (t, J )
6.0 Hz, 2H), 3.52 (t, J ) 6.0 Hz, 2H), 2.14 (quintet, J ) 6.0 Hz,
2H); 13C NMR (CDCl3, 100 MHz) δ 146.1, 131.9, 130.5, 129.8,
126.8, 118.6, 110.9, 33.1, 31.4, 29.7; MS (EI) m/z (relative
intensity) 250 (M+, 100), 221 (10), 176 (35), 146 (30), 106 (85).
3-(3-Meth yl-6,7-d ih yd r o-5H-[1,4]d ith iep in -2-yl)ben zon i-
1
tr ile (2b): method B; 79%; H NMR (CDCl3), 400 MHz) δ 7.58
(s,1H), 7.54-7.47 (m, 2H), 7.40 (t, J ) 7.6 Hz, 1H), 3.59-3.50
(m, 4H), 2.14 (quintet, J ) 5.8 Hz, 2H), 1.61 (s, 3H); MS (EI)
m/z (relative intensity) 247 (M+, 100), 218 (10), 173 (25), 140
(30), 106 (90), 73 (60). Anal. Calcd for C13H13S2N: C, 63.12; H,
5.30. Found: C, 63.31; H, 5.49.
4-(3-Met h yl-6,7-d ih yd r o-5H -[1,4]d it h iep in -2-yl)b en zoic
a cid m eth yl ester (2c): method A; 44%; 1H NMR (CDCl3, 400
MHz) δ 7.97 (d, J ) 9.0 Hz, 2H), 7.34 (d, J ) 9.0 Hz, 2H), 3.91
(s, 3H), 3.55 (t, J ) 5.6 Hz, 2H), 3.52 (t, J ) 5.6 Hz, 2H), 2.14
(quintet, J ) 5.6 Hz, 2H), 1.73 (s, 3H); 13C NMR (CDCl3, 100
MHz) δ 166.6, 146.1, 129.7, 129.4, 128.9, 128.7, 127.8, 55.2, 33.0,
31.5, 29.8, 24.6; MS (EI) m/z (relative intensity) 280 (M+, 50),
206 (20), 175 (22), 143 (25), 115 (40), 106 (100), 73 (98), 59 (65).
Anal. Calcd for C14H16S2O2: C, 59.97; H, 5.75. Found: C, 60.37;
H, 6.04.
4-(3-Meth yl-6,7-d ih yd r o-5H-[1,4]d ith iep in -2-yl)ben za ld e-
h yd e (2d ). Deprotection of the p-formyl group and dehydrative
ring expansion in the diethyl acetal of 1d were performed in
one step using 1 equiv of TsOH‚H2O: 65%; 1H NMR (CDCl3, 400
MHz) δ 9.98 (s,1H), 7.82 (d, J ) 8.6 Hz, 2H), 7.44 (d, J ) 8.1
Hz, 2H), 3.58-3.50 (m, 4H), 2.15 (quintet, J ) 5.8, 2H), 1.75 (s,
3H); MS (EI) m/z (relative intensity) 250 (M+, 100), 221 (10),
176 (12), 147 (15), 106 (60), 89 (10).
2-(4-Meth oxyph en yl)-3-m eth yl-6,7-dih ydr o-5H-[1,4]dith i-
1
ep in e (2f): method A; 31%; H NMR (CDCl3, 400 MHz) δ 7.18
(d, J ) 8.8 Hz, 2H), 6.82 (d, J ) 8.8 Hz, 2H), 3.78 (s, 3H), 3.50
(t, J ) 5.6 Hz, 2H), 3.48 (t, J ) 5.6 Hz, 2H), 2.09 (quintet, J )
5.6 Hz, 2H), 1.74 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 158.6,
133.5, 130.8, 128.7, 126.0, 113.4, 55.2, 32.7, 31.4, 29.7, 24.5;
MS (EI) m/z (relative intensity) 252 (M+, 100), 178 (40),
163 (40), 151 (35), 146 (75), 131 (35), 103 (40), 77 (38). Anal.
Calcd for C13H18S2O2: C, 61.86; H, 6.39. Found: C, 62.12; H,
6.58.
Gen er a l P h otoch em ica l P r oced u r e. The solution of an
appropriate methyldithiepine (5 mg) in 0.6 mL of CCl4 was
degassed by four freeze-pump-thaw cycles and sealed in a
Pyrex NMR tube. The irradiations were carried out in a carousel
Rayonet photoreactor. The sample was analyzed by NMR
immediately after the irradiation. In an alternative method, an
appropriate methyldithiepine (5 mg) was dissolved in 0.6 mL of
benzene-d6 containing 1 µL of concentrated aqueous HCl in a
Pyrex NMR tube. It was degassed, irradiated, and analyzed as
described above. Most of the acid and minor side products can
be removed by filtering the solution through a small pipet packed
with basic aluminum oxide.
1
4-(3-Meth ylen e[1,4]d ith iep a n -2-yl)ben zon itr ile (3a ): H
NMR (C6D6, 400 MHz) δ 7.09 (d, J ) 8.4 Hz, 2H), 6.95 (d, J )
8.4 Hz, 2H), 5.34 (s, 1H), 4.57 (s, 1H), 4.56 (s, 1H), 2.59-2.45
(m, 2H), 2.40-2.29 (m, 2H), 1.64-1.51(m, 2H); 13C NMR (C6D6,
100 MHz) δ 145.9, 144.8, 132.0, 129.3, 118.7, 118.5, 111.8,55.6,
33.6, 32.4, 30.4; MS (EI) m/z (relative intensity) 247 (M+, 20),
172 (10), 140 (15), 106 (100).
3-(3-Meth ylen e[1,4]d ith iep a n -2-yl)ben zon itr ile (3b): 1H
(C6D6, 400 MHz) δ 7.47 (s,1H), 7.33 (d, J ) 7.3 Hz,1H), 6.88 (d,
J ) 7.3 Hz, 1H), 6.65 (t, J ) 8.0 Hz, 1H), 5.32 (s, 1H), 4.56 (s,
1H), 4.54 (s, 1H), 2.59-2.52 (m, 2H), 2.39-2.29 (m, 2H), 1.63-
1.50 (m, 2H).
(14) Compound 2d was synthesized starting with the monodiethyl
acetal of terephthalic aldehyde. Under the conditions of acid-catalyzed
dehydrative ring expansion (1d -m on oa ceta l f 2d ), the acetal protec-
tion was also removed regenerating free formyl in the para-position
of 2d . We introduced the acetal into the second step without additional
purification.
4-(3-Meth ylen e[1,4]d ith iep a n -2-yl)ben zoic a cid m eth yl
ester (3c) :1H NMR (C6D6, 400 MHz) δ 8.08 (d, J ) 8.4 Hz, 2H),

Notes
J . Org. Chem., Vol. 66, No. 5, 2001 1899
7.43 (d, J ) 8.4 Hz, 2H), 5.38 (s, 1H), 4.757 (s, 1H), 4.71 (s, 1H),
4.48 (s, 3H), 2.69-2.56 (m, 2H), 2.51-2.35 (m, 2H), 1.66-1.55
(m, 2H); 13C NMR (C6D6, 100 MHz) δ 166.4, 146.5, 145.3,
130.6,129.0, 127.4, 117.9, 55.9, 51.8, 33.7, 32.0, 30.5; MS (EI)
m/z (relative intensity) 280 (M+, 10), 143 (13), 115 (15), 106 (100),
59 (10).
Ack n ow led gm en t. Support of this research by the
National Science Foundation (Career Award CHE-
9876389) is gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: NMR spectra and
computational details. This material is available free of charge
via the Internet at http://pubs.acs.org.
4-(3-Meth ylen e[1,4]d ith iep a n -2-yl)ben za ld eh yd e (3d ): 1H
(C6D6, 400 MHz) δ 9.62 (s, 1H), 7.49 (d, J ) 7.9 Hz, 2H), 7.38 (d,
J ) 8.2 Hz, 2H), 5.39 (s, 1H), 4.72 (s, 1H), 4.69 (s, 1H), 2.68-
2.55 (m, 2H), 2.53-2.36 (m, 2H), 1.60-1.48 (m, 2H).
J O005707I