Competition between Cyclization and Dehalogenation in the Photochemistry of Cinnamylphenols with Halogen Substituents at the Phenolic and Styrenic Chromophores

Full text of DOI:10.1021/jo971621m

J . Org. Chem. 1998, 63, 1323-1326
1323
excited-state proton transfer (ESPT) mechanism involv-
ing the excited singlet states of the phenol and styrene
chromophores. It has been speculated that formation of
dihydrobenzofuran 3a takes place from the phenolic
singlet, while dihydrobenzopyran 4a arises from the
styrenic singlet.3 In the present work, halogen sub-
stituents have been incorporated to both aromatic rings
with two main purposes: (i) to modify the relative
energies of both chomophores and (ii) to provide an
alternative pathway for deactivation of the excited states,
by means of the carbon-halogen bond cleavage. It was
expected that the substitution-dependent variations in
the product selectivity could help to confirm the above
excited-state assignment. In fact, the results show a
complete inhibition in the formation of five-membered
ring products when halogen is attached to the phenolic
ring. Besides, solvent-derived products involving cleav-
age of the carbon-halogen bond are obtained in a number
of cases. These facts constitute a convincing experimen-
tal support in favor of the initially proposed reaction
mechanism.
Com p etition betw een Cycliza tion a n d
Deh a logen a tion in th e P h otoch em istr y of
Cin n a m ylp h en ols w ith Ha logen
Su bstitu en ts a t th e P h en olic a n d Styr en ic
Ch r om op h or es
M. Consuelo J ime´nez, Miguel A. Miranda,* and
Rosa Tormos
Departamento de Quı´mica/ Instituto de Tecnologı´a Qu´ımica
UPV-CSIC, Camino de Vera s/ n, Apdo. 22012,
46071, Valencia, Spain
Received September 2, 1997
In tr od u ction
Bichromophoric compounds have attracted consider-
able interest as suitable models for the study of key
photochemical processes, such as energy or electron
transfer.1 Besides, they have found application in a
number of fields, including the reproduction of biological
phenomena (i.e. photosynthesis) or the design of new
materials (i.e. photoconducting polymers).2 Compounds
derived from trans-2-cinnamylphenol (1a ) are bichro-
mophoric systems containing phenolic and styrenic units,
connected through a methylene spacer. These systems
are simple and versatile models in which small structural
variations (such as substitution in both aromatics rings)
allow to control the photophysical and photochemical
behavior, reproducing at will intramolecular proton,
electron, or energy transfer.3,4
Resu lts a n d Discu ssion
The required cinnamylphenols were prepared by treat-
ment of 4-chloro- and 4-bromophenol with cinnamyl
chloride in strong basic medium (compounds 1b,c) or by
reduction of the corresponding 2-hydroxychalcones with
LiAlH4/AlCl3 in THF (compounds 1d ,e). Irradiation
experiments were carried out in benzene (using quartz-
filtered light) or in acetone (through Pyrex). All the
samples were thoroughly deoxygenated before irradia-
tion. The obtained results are presented in Table 1.
The photochemistry of the parent trans-2-cinnamylphe-
nol (1a ) has been investigated in some detail.3 The
products obtained upon irradiation of 1a are cis-2-
cinnamylphenol (2a), 2-benzyl-2,3-dihydrobenzofuran (3a),
and 2-phenyl-3,4-dihydro-2H-benzopyran (4a ). Photocy-
clization to 3a and 4a has been rationalized through an
The substrates substituted at the phenolic ring were
studied first. When the chloro derivative 1b5 was irradi-
ated in benzene, a mixture of the cis isomer 2b, the
dihydrobenzopyran 4b ,6 and the solvent-derived cyclic
4
ethers 3f4 and 4f (Table 1, entry 2) was obtained. In
the case of compound 1c, irradiation under the same
conditions led to 3f and 4c6,f (Table 1, entry 4). When
these results are compared with those previously ob-
tained for the parent compound trans-2-cinnamylphenol
(1a ),3 two differences appear particularly remarkable:
the absence of the five-membered ring products 3b,c and
the formation of cyclic derivatives related to trans-2-
cinnamyl-4-phenylphenol (1f).4 If photocyclization to
3b,c were to occur from the excited phenolic singlet, as
previously hypothesized, the existence of a new compet-
ing reaction pathway (cleavage of the carbon-halogen
bond) should result in a less efficient formation of such
products. Actually, this was found to be the case.
Thermodynamic considerations show that complete
C-X homolysis is possible upon excitation. Thus, the
singlet energies of compounds 1b,c, obtained from their
fluorescence spectra (see Table 2), were found to be 98
and 97 kcal/mol, respectively,7 while the corresponding
(1) Speiser, S. Chem. Rev. 1996, 96, 1953.
(2) Balzani, V.; Scandola, F. Supramolecular Photochemistry; Ellis
Horwood Limited: Chichester, 1991.
(3) J ime´nez, M. C.; Ma´rquez, F.; Miranda, M. A.; Tormos, R. J . Org.
Chem. 1994, 59, 197.
(4) J ime´nez, M. C.; Leal, P.; Miranda, M. A.; Tormos, R. J . Org.
Chem. 1995, 60, 3243.
(5) Ishino, Y.; Kaneko, Y.; Hirashima, T.; Nishiguchi, I. Kagaku to
Kogyo (Osaka) 1993, 67, 99 (Chem. Abstr. 1993, 119, 95024y).
(6) Bauer, D. J .; Selway, J . W. T.; Batchelo, J . F.; Tisdale, M.;
Caldwell, I. C.; Young, D. A. B. Nature (London) 1981, 292, 369.
(7) Similar values were found for 4-chlorophenol and 4-bromophenol
in Wehry, E. L.; Rogersm L. B. J . Am. Chem. Soc. 1965, 87, 4234.
S0022-3263(97)01621-6 CCC: $15.00 © 1998 American Chemical Society
Published on Web 02/05/1998

1324 J . Org. Chem., Vol. 63, No. 4, 1998
Notes
Ta ble 1. Ir r a d ia tion s of tr a n s-2-Cin n a m ylp h en ols 1a -e
than the energy required to break the chlorine-carbon
bond. On the other hand, the lack of an efficient pathway
for photochemical deactivation of the phenolic singlet
explains formation of the dihydrobenzofuran 3d , as in
the parent compound 1a .
Finally, direct photolysis of the brominated cinnamyl-
phenol 1e under the same conditions (Table 1, entry 8)
produced compounds 2e, 3g,16 and 4e,g.16 Only traces
of 3e were detected.17 Now, the energy content of the
excited singlet (91 kcal/mol, Table 2) is clearly high
enough to cleave the carbon-bromine bond. Thus, the
aryl radical II is formed, and then radical addition to the
solvent takes place. Again, the dihydrobenzopyran 4e
was irradiated under the same conditions; its photosta-
bility confirmed that photodehalogenation is the primary
photochemical step in the sequence of events leading to
4g.
As stated above for the analogues 1b,c with halogen
substituents at the phenolic ring, the only reaction
occurring from the excited triplet states of 1d ,e was found
to be trans to cis photoisomerization. This was assessed
by using acetone as photosensitizer (Table 1, entries 7
and 9).
In summary, the introduction of chlorine and bromine
in both the phenolic and the styrenic rings of a bichro-
mophoric cinnamylphenol produces a decrease of the
corresponding singlet excited-state energies. When such
energies lie above those required to cleave the carbon-
halogen bond, photodehalogenation (followed by solvent
addition) efficiently competes with photocyclization
(Scheme 1). This is specially remarkable in the case of
the compounds substituted at the phenolic chromophore,
where formation of dihydrobenzofurans is completely
prevented. These observations support the previous
assumption that the phenolic singlet gives rise to five-
membered ring compounds, while the styrenic singlet
leads to the isomeric six-membered ring analogues.
product yield (%)
entry compd condnsa conv
2
3
4
3f or 3g 4f or 4g
1
2
3
4
5
6
7
8
9
1a
1b
1b
1c
1c
1d
1d
1e
1e
A
A
B
A
B
A
B
A
B
80
55
70 100
40
60 100
49
53 100
42
60 100
25 45
35
30
30
30
25
60
32
47
10
10
54 14
18 tr 15
19
a
b
A; benzene, quartz; B; acetone, Pyrex. tr ) trace.
Ta ble 2. P h otop h ysica l Da ta of Com p ou n d s 1b-e a t
Room Tem p er a tu r e in Hexa n e (λexc ) 270 n m )
compd
λmax emission (nm)
ES (kcal/mol)
φF
1b
1c
1d
1e
310
311
322
325
98
97
92
91
0.001
<0.001
0.009
0.002
C-X bond energies in the model compounds chloroben-
zene and bromobenzene are only 95 and 75 kcal/mol.8 To
rule out the possibility that the benzene-derived products
could be formed by secondary photolysis of the halogen-
containing cyclic ethers, compounds 4b,c were submitted
to irradiation under the same conditions. No significant
reaction was observed in this control experiment, which
indicates that trans-2-cinnamyl-4-phenylphenol (1f) is
formed first, via addition of the aryl radical I to the
solvent. The subsequent photochemical transformation
of 1f into 3f and 4f is a known process.4
In principle, dehalogenation could also occur from an
excited triplet state. This appeared less likely, as the
values of triplet energies (ca. 60-70 kcal/mol)9 are too
low to fulfill the thermodynamic requirements, unless
some degree of C-C bond making occurs concomitantly
with C-X bond breaking.10 To check this point, photoly-
sis of 1b,c was carried out using acetone as photosensi-
tizer. Under these conditions, compounds 3f and 4f were
not formed, and the only process observed was trans/cis
isomerization (Table 1, entries 3 and 5). Hence, deha-
logenation does not appear to take place from an excited
triplet.11-14
Exp er im en ta l Section
UV spectra were recorded in cyclohexane; λmax (nm) and log ꢀ
values (in parentheses) are given for each absorption band. IR
spectra were obtained with a GC-FTIR instrument; νmax (cm-1
)
is given for all the absorption bands. 1H NMR spectra were
measured in CDCl3 with 300-MHz instrument; chem-
a
In a second stage of the work, the cinnamylphenols
subtituted at the styrenic ring were investigated. When
compound 1d , bearing a chlorine, was photolyzed in
benzene through quartz (Table 1, entry 6), the reaction
mixture was found to contain the cis isomer 2d , together
with the cyclic ethers 3d and 4d .6 In this case, no
products derived from reaction of 1d with the solvent
were observed, which is in agreement with the fact that
the singlet energy (92 kcal/mol, see Table 2)15 is lower
ical shifts are reported in δ (ppm) values, using TMS as inter-
nal standard. Mass spectra were obtained under electron
impact; the ratios m/z and the relative intensities (%) are
indicated for the significant peaks. Fluorescence spectra were
recorded in hexane. Isolation and purification were done by
conventional column chromatography on silica gel using dichlo-
romethane as eluent or by means of isocratic HPLC equipment
provided with a semipreparative column, using hexane/ethyl
acetate as eluent.
Gen er a l Ir r a d ia tion P r oced u r e. Solutions of 0.02 g of the
substrates in 20 mL of benzene or acetone were placed into
quartz or Pyrex tubes surrounding a centrally positioned quartz
cooling jacket containing a 125 W medium-pressure Hg lamp
and irradiated under argon for 1 h. The reaction mixtures were
analyzed by GC-MS and 1H NMR.
(8) Murov, S. L.; Carmichael, I.; Hug, G. L. Handbook of Photo-
chemistry; Marcel Dekker, Inc.: New York, 1993; p 280.
(9) Murov, S. L.; Carmichael, I.; Hug, G. L. Handbook of Photo-
chemistry; Marcel Dekker, Inc.: New York, 1993; p 78.
(10) Grimshaw, J .; de Silva, A. P. Chem. Soc. Rev. 1981, 10, 181.
(11) An additional possibility would be triplet-state dehalogenation
via formation of excimers.12-14 Although the contribution of this route
cannot be ruled out at the present stage of the work, it appears less
likely in view of the close relationship between lack of dehalogenation
and singlet energy deficit.
Syn th esis of th e Su bstr a tes a n d th e New Com p ou n d s.
P r ep a r a t ion of t h e Su b st r a t es 1b ,c.3,18 The sodium salt
(15) A similar value was found for 4-chlorostyrene in Brede, O.;
David, f.; Steenken, S. J . Photochem. Photobiol. A: Chem. 1996, 97,
(12) Soumillon, J . P.; De Wolf, B. J . Chem. Soc., Chem. Commun.
1981, 436.
(13) Freeman, P. K.; Ramnath, N.; Richardson, A. D. J . Org. Chem.
1991, 56, 3643.
127.
(16) J ime´nez, M. C.; Miranda, M. A.; Tormos, R. Tetrahedron 1997,
53, 14729.
(17) MS spectra data for 3e: 290 (M+ 81Br), 7), 288 (M+ 79Br), 8),
( (
(14) Freeman, P. K.; J ang, J .-S., Ramnath, N. J . Org. Chem. 1991,
56, 6072.
237 (6), 119 (100), 118 (28), 117 (8), 92 (9), 91 (52), 89 (12), 78 (4), 77
(7).

Notes
J . Org. Chem., Vol. 63, No. 4, 1998 1325
Sch em e 1
obtained from 40.0 mmol of 4-chloro- or 4-bromophenol was
added to trans-cinnamyl chloride (6.10 g, 40.0 mmol) in 100 mL
of benzene. After the mixture was refluxed for 5 h, the solvent
was distilled and the residue was treated with 100 mL of
Claisen’s alkali (35.00 g of potassium hydroxide in 25 mL of
water and methanol up to 100 mL). The alkaline solution was
washed with hexane, acidified with HCl, and extracted with
methylene chloride. Evaporation of the solvent gave a residue
which was submitted to column chromatography.
8 Hz, 1H), 6.74 (t, J ) 8 Hz, 1H), 6.26-6.34 (m, 2H), 5.31
(s, 1H), 3.49 (d, J ) 6 Hz, 2H); MS 246 (M+(37Cl), 24), 246,
(M+(35Cl), 72), 209 (70), 138 (100), 131 (34), 119 (79), 115 (55),
107 (20), 91 (58), 89 (30), 77 (43); exact mass calcd for
C15H1335ClO 244.0655, found 244.0661.
tr a n s-2-[3-(4-Br om op h en yl)-2-p r op en yl]p h en ol
(1e)
(55%): UV 260 (4.2), 215 (4.1); FTIR 3650 (OH), 3589 (OH),
3076, 3032, 2914, 1588, 1488, 1321, 1254, 1207, 1075, 1011, 966,
1
832, 748; H NMR: 7.19-7.40 (m, 2H), 7.21 and 7.38 (AA′BB′,
P r ep a r a tion of th e Su bstr a tes 1d ,e. The cinnamylphenols
1d ,e were prepared by reduction of the corresponding trans-2-
hydroxychalcones (previously synthesized by condensation of
2-hydroxyacetophenone with 4-chloro or 4-bromobenzaldehyde)19
with LiAlH4/AlCl3, using tetrahydrofuran as solvent.20 Final
purification was done by column chromatography.
Alter n a tive Syn th esis of Com p ou n d 3d . (Z)-2-[(4-Chlo-
rophenyl)methylene]-3(2H)-benzofuranone21 (1.0 mmol) in ethyl
acetate (25 mL) was hydrogenated in the presence of palladium/
charcoal (11%) until consumption of 75 mL of hydrogen. The
solution was filtered and on evaporation afforded the pure
dihydrobenzofuran 3d in quantitative yield.
4H), 6.93 (t, J ) 8 Hz, 1H), 6.81 (t, J ) 8 Hz, 1H), 6.39 (m, 2H),
4.85 (s, 1H), 3.54 (d, J ) 6 Hz, 2H); MS 290 (M+(81Br), 25), 288,
(M+(79Br), 27), 209 (70), 184 (71), 182 (66), 131 (48), 119 (97),
115 (94), 91 (100), 77 (82); exact mass calcd for C15H1379BrO
288.0150, found 288.0141.
cis-4-Ch lor o-2-cin n a m ylp h en ol (2b): UV 283 (3.3), 247 (sh,
3.7), 215 (4.1); FTIR 3651 (OH), 3590 (OH), 3069, 3027, 1598,
1488, 1412, 1310, 1258, 1204, 1161, 1109, 914, 810, 757; 701;
1H NMR 7.05-7.39 (m, 8H), 6.70 (d, J ) 12 Hz, 1H), 5.81 (dt, J 1
) 12 Hz, J 2 ) 7 Hz, 1H), 5.02 (s, 1H), 3.61 (d, J ) 7 Hz, 2H);
MS 246 (M+ 37Cl), 18), 244 (M+ 35Cl), 49), 209 (63), 165 (27),
( (
153 (46), 152 (31), 131 (28), 115 (65), 91 (72), 77 (60). Anal. Calcd
for C15H13ClO: C, 73.59; H, 5.35; Cl, 14.51. Found: C, 73.21;
H, 5.46; Cl, 13.82.
tr a n s-4-Br om o-2-cin n a m ylp h en ol (1c) (43%): oil.;UV 284
(3.4), 227 (sh, 4.0), 216 (4.1); FTIR 3651 (OH), 3559 (OH), 3070,
3032, 1485, 1409, 1308, 1258, 1205, 1160, 1105, 966, 812, 733,
cis-4-Br om o-2-cin n a m ylp h en ol (2c): UV 283 (3.4), 230
(4.1), 216 (4.1); FTIR 3650 (OH), 3585 (OH), 3068, 3025, 1598,
1485, 1407, 1307, 1258, 1202, 1161, 1103, 873, 809, 700, 628;
1
628; H NMR 7.19-7.36 (m, 7H), 6.67 (d, 1H), 6.49 (d, J ) 16
Hz, 1H), 6.31 (dt, J 1 ) 16 Hz, J 2 ) 6 Hz, 1H), 5.14 (s, 1H), 3.50
(d, J ) 6 Hz, 2H); MS 290 (M+(81Br), 43), 288, (M+(79Br), 43),
209 (100), 199 (22), 197 (23), 131 (19), 118 (29), 115 (23), 104
(48), 91 (19), 77 (18). Anal. Calcd for C15H13BrO: C, 62.30; H,
4.53; Br, 27.63. Found: C, 62.25; H, 4.46; Br, 26.95.
1H NMR 7.25-7.40 (m, 7H), 6.65-6.70 (m, 2H), 5.81 (dt, J 1
)
12 Hz, J 2 ) 7 Hz, 1H), 4.92 (s, 1H), 3.61 (d, J ) 7 Hz, 2H); MS:
290 (M+ 81Br), 11), 288 (M+ 79Br), 12), 209 (35), 118 (36), 115
(
(
(38), 104 (100), 91 (80), 78 (26), 77 (36), 51 (29). Anal. Calcd
for C15H13BrO: C, 62.30; H, 4.53; Br, 27.63. Found: C, 62.22;
H, 4.49; Br, 27.35.
tr a n s-2-[3-(4-Ch lor op h en yl)-2-p r op en yl]p h en ol
(1d )
(45%): UV 259 (3.9), 219 (3.8); FTIR 3650 (OH), 3585 (OH), 3075,
3033, 2914, 1590, 1491, 1321, 1254, 1207, 1095, 1014, 966, 834,
748; 1H NMR 7.20 (AA′BB′, 4H), 7.14-7.18 (m, 2H), 6.88 (t, J )
cis-2-[3-(4-Ch lor op h en yl)-2-p r op en yl]p h en ol (2d ): UV
248 (3.9), 219 (3.9); FTIR 3649 (OH), 3601 (OH), 3075, 3026,
1589, 1490, 1401, 1321, 1255, 1203, 1093, 1015, 841, 748; 1H
NMR 7.25 and 7.30 (AA′BB′, 4H), 7.08-7.15 (m, 2H), 6.88 (dt,
J 1 ) 7 Hz, J 2 ) 1 Hz, 1H), 6.76 (d, J ) 8 Hz, 1H), 6.56 (d, J )
12 Hz, 1H), 5.81 (dt, J 1 ) 12 Hz, J 2 ) 7 Hz, 1H), 4.82 (s, 1H),
3.61 (dd, J 1 ) 7 Hz, J 2 ) 2 Hz, 2H); MS 246 (M+(37Cl), 29), 246,
(M+(35Cl), 75), 209 (100), 165 (24), 140 (28), 138 (83), 131 (40),
(18) Tarbell, D. S. The Claisen Rearrangement. In Organic Reac-
tions; Adams, R., Ed.; J ohn Wiley & Sons: New York, 1944; Vol. 2, p
28.
(19) Poonia, N. S. Chhabra, K.; Kumar, C.; Bhagwat, V. W. J . Org.
Chem. 1977, 42, 3311.
(20) Bokadia, M. M.; Brown, B. R.; Cobern, D.; Roberts, A.; Somer-
field, G. A. J . Chem. Soc. 1962, 1658.
(21) Varma, R. S.; Varma, M. Tetrahedron Lett. 1992, 33, 5937.
119 (45), 115 (67), 91 (56), 77 (49); exact mass calcd for C15H13
-
35ClO 244.0655, found 244.0649.

1326 J . Org. Chem., Vol. 63, No. 4, 1998
Notes
cis-2-[3-(4-Br om op h en yl)-2-p r op en yl]p h en ol (2e): UV
251 (4.2), 216 (4.0); FTIR 3650 (OH), 3601 (OH), 3075, 3026,
2914, 1587, 1488, 1402, 1321, 1255, 1203, 1075, 1040, 1012, 839,
786, 748; 1H NMR 7.19 and 7.47 (AA′BB′, J ) 8 Hz, 4H), 7.09-
7.15 (m, 2H), 6.89 (dt, J 1 ) 7 Hz, J 2 ) 1 Hz 1H), 6.77 (t, J ) 8
Hz, 1H), 6.54 (d, J ) 11 Hz, 2H), 5.88 (dt, J 1 ) 11 Hz, J 2 ) 7
Hz, 2H), 4.81 (s, 1H), 3.61 (dd, J 1 ) 7 Hz, J 2 ) 2 Hz, 2H); MS
290 (M+(81Br), 27), 288, (M+(79Br), 28), 209 (72), 184 (67), 182
(73), 171 (41), 169 (43), 131 (47), 119 (100), 91 (87), 77 (71); exact
mass calcd for C15H1379BrO 288.0150, found 288.0140.
120 (9), 119 (100), 118 (16), 91 (49), 77 (4); exact mass calcd for
C
15H1335ClO 244.0655, found 244.0646.
Ack n ow led gm en t. Financial support by the DGI-
CYT (PB 94-0539) to M.A.M. and fellowships to M.C.J .
and R.T. (PR95-509) are gratefully acknowledged. We
also thank Prof. J . C. Scaiano (University of Ottawa,
Ottawa, Canada) for the facilities in the fluorescence
measurements and to Dr. Lydia Mart´ınez for her helpful
comments on the fluorescence spectra.
2-(4-Ch lor oben zyl)-2,3-d ih yd r oben zofu r a n (3d ): FTIR
3079, 2950, 1598, 1483, 1229, 1169, 1096, 1015, 986, 869, 796,
745; 1H NMR 7.55-6.69 (m, 8H), 4.91 (m, 1H), 3.14 (m, 2H),
2.89 (m, 2H); MS 246 (M+(37Cl), 4), 244 (M+(35Cl), 12), 125 (9),
J O971621M