Photoinduced [4 + 2] cycloaddition reactions of benzo[bi]thiophene-2,3- dione with alkenes

Article abstract of DOI:10.1007/s11164-011-0411-y

[4 + 2]-Photocycloadditions of benzo[b]thiophene-2,3-dione with electron-rich and electron-deficient alkenes have been described. Olefins preferentially add at both carbonyl groups to give the head-to-head [4 + 2] cycloadducts, i.e., dioxanes only. Compre

Full text of DOI:10.1007/s11164-011-0411-y

Res Chem Intermed (2012) 38:723–731
DOI 10.1007/s11164-011-0411-y
Photoinduced [4 + 2] cycloaddition reactions
of benzo[b]thiophene-2,3-dione with alkenes
•
Sonali Verma Barkha Srivastava Kusum Sharma
•
•
•
Rahul Joshi Pushpa Pardasani R. T. Pardasani
•
Received: 11 July 2011 / Accepted: 20 September 2011 / Published online: 5 October 2011
Ó Springer Science+Business Media B.V. 2011
Abstract [4 ? 2]-Photocycloadditions of benzo[b]thiophene-2,3-dione with
electron-rich and electron-deficient alkenes have been described. Olefins preferen-
tially add at both carbonyl groups to give the head-to-head [4 ? 2] cycloadducts,
i.e., dioxanes only. Comprehensive molecular orbital calculations at DFT-B3LYP
level have been carried out to address the mechanism as well as regiochemical
course of the reaction.
Keywords Photocycloaddition Á Thioisatin Á Dioxanes Á Regioselectivity Á
DFT calculations Á Intermediate biradicals
Introduction
Over the last three decades, the photochemistry of organic molecules has grown
into an important and pervasive branch of organic chemistry [1, 2]. Photochemical
cycloaddition provides one of the most efficient and versatile methods for the
construction of carbo- and hetero-cycles of different sizes with high atom economy
[3]. Carbonyl compounds constitute a major type of substrates in photocycload-
ditions. Most commonly, photochemical reactions of carbonyl compounds are
classified to cleavage reactions, hydrogen abstractions, and cycloaddition [4, 5]. The
[4 ? 2] cycloaddition reactions constitutes one of the most frequently employed
synthetic method for the construction of highly regio- and enatio-selective
six-membered and polycyclic ring systems [6–8]. Over the past three decades,
numerous photocycloaddition reactions have been carried out on a-diketones [9] but
most of these studies are limited to understanding the electronic structure of the
species rather than understanding the mechanism as well as theoretical studies of the
S. Verma Á B. Srivastava Á K. Sharma Á R. Joshi Á P. Pardasani Á R. T. Pardasani (&)
Department of Chemistry, University of Rajasthan, Jaipur 302 055, India
e-mail: rtpardasani@gmail.com
123

724
S. Verma et al.
reactions [10]. Chow and coworkers [11] have described the photoadditions of
a-diketones yet the fascinating photochemistry of benzo[b]thiophenes has remained
largely unexplored. Synthetically numerous reactions of thioisatin have been
described [12] but to our knowledge, photochemically no reaction has been
explored. Motivated by our recent works on stereoselectivity in [3 ? 2] cycload-
ditions of azomethine ylides [13, 14] and photochemistry of quinones and their
[2 ? 2/[3 ? 2] photocycloadditions [15–18], we have examined photocyclo-
addition reactions of benzo[b]thiophene-2,3-diones with various electron-rich and
electron-deficient alkenes. The synthetic results complemented by computational
study are presented herein.
Experimental
General
Melting points were determined in an open-glass capillary and are uncorrected.
The solvents were purified by standard procedures [19, 20]. The IR spectra were
recorded on Nicolet Magna IR TM model 550 in KBr pellets. The 1H and 13C NMR
spectra were obtained on a JEOL AL-300 instrument at 300 and 75 MHz using
CDCl3 or DMSO-d6 as solvent and tetramethylsilane (TMS) as an internal standard.
Chemical shifts are given in d ppm. Elemental analyses were performed by
Perkin-Elmer series C, H, N, and S analyser-2400. Photochemical irradiation was
conducted in a Heber multilamp photoreactor (Model: HML-COMPACT-SW-MW-
LW888) consisting of a quartz/borosilicate reactor surrounded by 8 ? 8 ? 8
numbers of UV lamps (eight lamps can be operated at a time: either at 254/312/
365 nm with 8 ? 8 ? 8 separate controls) permanently fixed inside the reaction
chamber with a built-in highly polished anodized aluminium reflector (85%
reflection) so that UV rays are focused at the center where the sample is kept.
The reaction chamber is covered by a reactor house that does not allow leakage of
any UV irradiation. Thin-layer chromatography (TLC) was performed on alumina
foil on Merck’s Kiesel gel 60 F254 sheets, visualization was achieved at ultra
fluorescence on an Indian Equipment Corporation equipment, IEC-312 at 354 nm.
Column chromatography was carried over silica gel 60–120 mesh as absorbent,
using solvents of rising polarity.
Computational details
All computations were performed via different theoretical methods by using the
Gaussian 03 suite of programs [21]. The optimization of the geometries and
population analysis were carried out using generalized gradient approximation
Becke3-Lee-Yang-Parr (B3LYP) level of theory with 6–31G basis set. Harmonic
vibration frequencies of all stationary points have been computed to characterize
them as energy minima (all frequencies are real) or transition states (one and only
one imaginary frequency). An imaginary frequency has been obtained for each
transition state, which substantiates the actual formation of the transition state.
123

Reactions of benzo[b]thiophene-2,3-dione with alkenes
725
Intrinsic reaction coordinates (IRC) calculation was carried out to confirm the
reaction pathway and the transition state.
General procedure for synthesis
3-Phenyl-2,3-dihydro-1,4-dioxo-9-benzo[b]thiophene 3a A solution of benzo[b]-
thiophene-2,3-dione 1 (0.36 g, 2.0 mmol) and styrene 2a (0.2 g, 2.0 mmol) in dry
benzene (35 ml) was placed in a quartz tube and irradiated at 312 nm under nitrogen
atmosphere using Heber Multilamp photoreactor for 16 h with magnetic stirring.
After completion of the reaction as monitored by TLC, the concentration of the
reaction mixture under reduced pressure furnished the product 3a as a brown mass,
which was purified by column chromatography over silica gel. The petroleum ether-
choroform (2:8) fraction afforded a brown solid.
Brown solid, mp. 138–140 °C. IR (KBr) mmax: 3020 (Ar-H), 1650 (C=C), 1050
(C–O–C), 670 (C–S) cm-1.1H-NMR (CDCl3) d 7.45–7.86 (m, 4H, Ar-H), 7.14
(m, 5H, Ar-H), 5.21(s, 1H, H-3), 3.54 (dd, 2H, H-2, J = 3.51 Hz, J = 1.4 Hz).
13C-NMR (CDCl3) d 135.14–128.32 (Ar-C), 121.25–122.48 (C=C), 54.55 (C-2),
61.43 (C-3).
Anal. calcd for C16 H12O2S: C, 72.31; H, 5.01; S, 11.36; O, 11.33. Found: C,
71.45; H, 4.78; S, 10.46; O, 10.21.
2,3-Diphenyl-2,3-dihydro-1,4-dioxo-9-benzo[b]thiophene 3b Brown solid, mp.
152–154 °C. IR (KBr) mmax: 3025 (Ar-H), 1615 (C=C), 1030 (C–O–C), 665
(C–S).1H-NMR (CDCl3) d: 7.32–7.89 (m, 4H, Ar-H), 7.18 (s, 10H, Ar-H), 4.54 (dd,
2H, H-2,H-3 J = 4.72 Hz, J = 1.8 Hz). 13C-NMR (CDCl3) d 138.14–131.32
(Ar-C), 122.41–121.48 (C=C), 61.82 (C-2, C-3).
Anal. calcd for C22 H16O2S: C, 77.07; H, 5.06; S, 8.95; O, 8.93. Found: C, 67.78;
H, 4.12; S, 8.06; O, 8.01.
3-Bromo-3-methyl-2,3-dihydro-1,4-dioxo-9-benzo[b]thiophene 3c Shiny brown
solid, mp. 105–103 °C. IR (KBr) mmax: 3025 (Ar-H), 1665 (C=C), 1100 (C–O–C),
670 (C–S) 550 (C–Br).1H- NMR (CDCl3) d 7.48–7.97 (m, 4H, Ar-H), 4.45 (s, 2H,
H-2), 2.25 (s, 3H, H-3).13C NMR (CDCl3) d 134.36–129.32 (Ar-C), 123.25–122.58
(C=C), 59.91 (C-2), 63.03 (C-3), 18.91 (CH3).
Anal. calcd. (%) for C11 H9BrO2S: C, 48.17; H, 3.71; S, 10.72; O, 10.70. Found :
C, 48.03; H, 3.71; S, 9.98; O, 9.85.
3-Chloro-3-methyl-2,3-dihydro-1,4-dioxo-9-benzo[b]thiophene 3d Chocolate-brown
solid, mp. 112–110 °C. IR (KBr) mmax: 3045 (Ar-H), 1670 (C=C), 1055 (C–O–C),
1
760 (C–Cl) 665 (C–S). H-NMR (CDCl3 d 7.54–7.88 (m, 4H, Ar-H), 4.36 (s, 2H,
H-2), 2.32 (s, 3H, H-3).13C-NMR (CDCl3) d 134.32–129.41 (Ar-C), 124.46–123.58
(C=C), 55.01 (C-2), 65.03 (C-3) 20.01 (CH3).
Anal. calcd. for C11 H9ClO2S: C, 56.50; H, 4.35; S, 12.59; O, 12.56. Found: C,
55.58; H, 4.03; S, 11.98; O, 11.76.
123

726
S. Verma et al.
1,4-Dioxo-9-benzo[b]thiophene-2,2,-3,3,tetracarbonitrile 3e Buff solid, mp.
120–115 °C. IR (KBr) mmax : 3025 (Ar-H), 2265 (C:N) 1675 (C=C), 1105 (C–
O–C), 675 (C–S).
1H-NMR (CDCl3) d 7.45–7.89 (m, 4H, Ar-H). 13C-NMR (CDCl3) d
134.94–129.32 (Ar-C), 123.58–122.43 (C=C), 118.43–117.21 (C:N), 59.38 (C-2,
C-3).
Anal. calcd. for C14H4N4O2S: C, 58.82; H, 1.97; S, 10.47; O, 10.45. Found: C,
57.78; H, 1.09; S, 9.48; O, 9.56.
Results and discussion
The photocycloaddition reaction of thioisatin 1 with different alkenes 2 (styrene,
trans-stilbene, 2-bromopropene, 2-chloropropene and tetracyanoethylene) was
carried out under a nitrogen atmosphere in dry benzene with constant magnetic
stirring in Heber photoreactor with medium pressure mercury arc lamp at 312 nm
(Fig. 1). The photochemical reaction was continued for 22 h until no further
thioisatin was consumed. Subsequently, the reaction mixture was evaporated and
the crude products purified by column chromatography over silica gel to afford
photoadducts in 46–68% yield.
The structure of the cycloadducts 3a–e has been ascertained from their spectral
data. All the spectral data are in harmony with the assigned structures. On the basis
of detailed NMR analysis, it has been unambiguously concluded that in all cases
head-to-head 1,4-dioxane adducts are formed discarding the possibility of formation
`
of [2 ? 2] Paterno–Bu¨chi adducts.
Regio- and stereoselectivity of the photocycloaddition reaction
The regio- and stereoselectivity of the [4 ? 2] photocycloaddition reactions has
been investigated in detail by DFT molecular orbital calculations. In this study,
R1
R2
O
O
R3
R4
R1
R3
R2
R4
hv
O
O
dry benzene
S
S
1
3a-e
2a-e
2a: R1=R3=R4 =H ; R2 = C6H 5
2b: R1=R3=C6H5 ; R4 =R2 = H
2c: R1= CH 3 ; R2= Br; R3 =R4 = H
2d: R1= CH3 ; R2= Cl; R 3 =R4 = H
R1=R2=R3=R4 =CN
2e:
Fig. 1 Reaction of thioisatin with different alkenes
123

Reactions of benzo[b]thiophene-2,3-dione with alkenes
727
H
C6H5
C6H5
H
H
O
O
H
H
H
O
H
O
O
S
S
hv
3a (ii)
3a (i)
O
C6H5
C
H
CH2
dry benzene
S
H
1
2a
H
H
O
O
H
C6H5
H
C6H5
O
O
S
S
3a (iv)
3a (iii)
Fig. 2 Possible head-to-head and head-to-tail photocycloadducts 3a(i)–3a(iv)
photocycloaddition of thioisatin with styrene was chosen as the model reaction.
The attack of styrene on thioisatin results in the formation of four isomers 3a(i)–(iv)
(Fig. 2). Among them 3a(i) and 3a(ii) are head-to-head regioisomers while 3a(iii)
and 3a(iv) are head-to-tail photoadducts.
The geometry and energy of all four regioisomers have been optimized at DFT-
B3LYP level. The optimized geometries of all the isomers are shown in Fig. 3 and
the relative energies are presented in Table 1.
It is evident from Table 1 that the head-to-head regioisomers 3a(i) and 3a(ii)
are thermodynamically more stable than the head-to-tail regioisomers. The proximity
of the bulky phenyl group to sulfur atom may be attributed to the relative
destabilization of head-to-tail adducts. Again, among the stereoisomers 3a(i) and
3a(ii), the latter is slightly more favored due to its higher stabilization energy. The
minimization of steric repulsion of phenyl group in 3a(ii) may lead to its enhanced
stability. The transition state geometries of 3a(i) and 3a(ii) given in Fig. 4.
Mechanism of the photocycloaddition reaction
The next task was to illustrate a feasible mechanism for the formation of 3a(ii).
A plausible mechanism has been proposed for the [4 ? 2] photocycloaddition
reaction and is depicted in Fig. 5.
Generally, the photocycloadditions of a-diketones occur via triplet excited states
[9]. In this mechanistic pathway, the photocycloaddition reaction is proposed to
proceed through triplet biradical intermediates. Thioisatin 1 is excited to its triplet
state leading to the formation of a triplet biradical t1. The attack of dienophile
styrene 2a on triplet biradical t1 can take place via two different pathways. In path
‘a’ the attack of styrene takes place on the oxygen far from sulfur (O1) generating
intermediate triplet biradical t2 and in path ‘b’ styrene first attacks on the oxygen
near to sulfur (O2) yielding another intermediate triplet biradical t3. Further, both t2
and t3 may cyclize to give the photocycloadduct 3a(ii). All the ground state
reactants and products as well as intermediate triplet biradicals and transition states
have been optimized at DFT-B3LYP level to estimate their energy and to predict the
feasible mechanistic pathway. The results are summarized in Table 2.
123

728
S. Verma et al.
Fig. 3 Optimized geometries of the possible regioisomers 3a(i)–3a(iv)
Table 1 Relative energies of
Regioisomer
Relative energy* (Kcal/mol)
the regioisomers 3a(i)–3a(iv)
3a(i)
-11.86
-13.80
-00.50
-04.02
3a(ii)
3a(iii)
3a(iv)
*Relative to reactants (1 1 2a)
Fig. 4 Transition-state geometries of the head-to-head photocycloadducts 3a(i) and 3a(ii)
123

Reactions of benzo[b]thiophene-2,3-dione with alkenes
729
C6H5
H
O
H
H
O
H
H
S
t2
C6H5
H
C6H5
path a
O
path a
O
O
1
H
H
H
hv
O
H
C6H5
O
O
2
2a
S
O
path b
S
S
H
H
3a(ii)
path b
1
t1
O
S
t 3
Fig. 5 Proposed mechanism for [4 ? 2] photocycloaddition reaction
Table 2 Energy of reactants,
Species
Energy (Eh)
biradical intermediate, and
transition states computed at
1
-855.7840
-309.5790
-1165.2643
-1165.2921
-1165.3854
-1165.3025
-1165.3058
B3LYP level of calculation
corresponding to attack of
styrene
2a
t2
t3
3a(ii)
TS [t2/3a(ii)]
TS [t3/3a(ii)]
The triplet radical t2 is a primary biradical while t3 is a secondary biradical.
Also, the energy of t3 is found to be lower than that of t2 (Table 2). Subsequently,
the formation of intermediate biradical t3 via path ‘b’ is expected to be more
feasible. This is further substantiated by transition state studies. The transition states
for the final step t2 ? 3a(ii) or t3 ? 3a(ii) conversion have been located.
The calculations showed that the transition state energy is lower for t3 ? 3a(ii)
conversion. The potential energy diagrams for these conversions and transition state
geometries are given below in Figs. 6 and 7.
The potential energy barrier for t3 ? 3a(ii) conversion is 58.55 kcal/mol while
that of t2 ? 3a(ii) conversion is 76.0 kcal/mol. This clearly indicates that the
photocycloaddition proceeds via the secondary biradical t3 to yield the final
cycloadduct 3a(ii).
Conclusions
A series of novel 1,4-dioxane derivatives were synthesized by [4 ? 2]-photocyclo-
additions of thioisatin with different dienophiles. DFT-B3LYP studies have been
employed to understand the regioselectivity of [4 ? 2] photocycloaddition reaction
that leads to the formation of six-membered head-to-head dioxane derivatives
123

730
S. Verma et al.
58.55 Kcal/mol
76.0 Kcal/mol
t3
t2
3a(ii)
3a(ii)
Fig. 6 Potential energy barrier diagram for intermediate biradicals t2 and t3
Fig. 7 Transition-state geometries of the intermediate biradicals t2 and t3
predominantly. The mechanism of the reaction pathway is also illustrated by
transition state studies.
Acknowledgments We are grateful to University Grants Commission, New Delhi for financial
assistance.
References
1. Y. Inove (ed.), Chiral photochemistry (V. Ramamurthy, M. Dekker, New York, 2004)
2. H.A.J. Carless, In Synthetic Organic Chemistry, ed. by W.H. Horspool (Plenum Press, New York
1984), p. 425
3. H.A.J. Carless, in Photochemistry in Organic Synthesis, vol. 56, (ed.) by J.D. Coyle, (The Royal
Society of Chemistry, Special Publication, London, 1986), p. 95
4. N.D. Epiotis, J. Am. Chem. Soc. 94, 1946 (1972)
5. N.C. Lucas, M.T. Silva, C. Gege, J.C. Netto-Ferria, J. Chem. Soc. Perkin Trans. 2, 2795 (1999)
6. F.W. Lichtenthaler, T. Weimer, S. Immel, Tetra. Assym. 15, 2703 (2004)
7. G. Jones, in Organic Photochemistry, vol. 5, ed. by A. Padwa, M. Dekker, (New York 1981)
123

Reactions of benzo[b]thiophene-2,3-dione with alkenes
731
8. CRC Handbook of Organic Photochemistry and Photobiology, 2nd edn. ed. by W. Horspool, F Lenci,
(CRC Press, London 2004)
9. A.K. Mukherjee, P. Margarettia, W.C. Agosta, J. Org. Chem. 61, 3388 (1996)
10. K. Maruyama, M. Murwka, Y. Naruta, J. Org. Chem. 46, 983 (1981)
11. Y.L. Chow, T.C. Joseph, H.H. Quon, J.N.S. Tam, J. Can. Chem. 48, 3045 (1970)
12. M. Rajopadhye, F.D. Popp, Heterocycles 27, 1489 (1988)
13. S. Verma, J. George, S. Singh, P. Pardasani, R.T. Pardasani, Org. Med. Chem. Lett. Accepted 2011
14. K. Arora, D. Singh, A. Gumber, R.S. Gupta, R.T. Paradasani, P. Pardasani, Heteroat. Chem. 20, 379
(2009)
15. I. Abraham, R. Joshi, P. Pardasani, R.T. Pardasani, J. Braz. Chem. Soc. 22, 385 (2011)
16. G. Sharma, I. Abraham, R.T. Pardasani, P.V. Bharatam, T. Mukherjee, Bull. Chem. Soc. Jpn. 82,
1477 (2009)
17. G. Sharma, I. Abraham, R.T. Pardasani, M.K. Pathak, T. Mukherjee, Res. Chem. Intermed. 35, 219
(2009)
18. R.T. Pardasani, P. Pardasani, S.K. Yadav, P.V. Bharatam, J. Heterocycl. Chem. 40, 557 (2003)
19. D.D. Perrin, W.L.F. Armarego, D.R. Perrin, Purification of Laboratory Chemicals, 2nd edn.
(Pergamon Press, Oxford, 1998)
20. A.I. Vogel, Vogel’s Text Book of Practical Organic Chemistry, 4th edn. (ELBS Longman, London,
1984)
21. Gaussian 03 Revision D.O.I, M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb,
J.R. Cheeseman, J.A. Montgomery, Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam,
S.S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A. Petersson,
H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima,
Y. Honda,O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox, H. P. Hratchian, J.B. Cross, V. Bakken,
C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi,
C. Pomelli, J. W.Ochterski, P.Y. Ayala, K. Morokuma, G.A. Voth, P. Salvador, J.J. Dannenberg,
V.G. Zakrzewski, S. Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck,
K. Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J. Cioslowski,
B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L. Martin, D.J. Fox, T. Keith,
M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen,
M.W. Wong, C. Gonzalez, and J.A. Pople, Gaussian 98, revision A.5; Gaussian, Inc.: Pittsburgh,
PA (1998)
123