A new route to multifunctionalized p-terphenyls and heteroaryl analogues via [5C + 1C(N)] annulation strategy

Article abstract of DOI:10.1021/jo802318p

p-Terphenyls and heteroaryl analogues including bipyridines were prepared via [5C + 1C(N)] annulation of α-aryl-α- alkenoyl ketene-(S,S)-acetals (five carbon 1,5-bielectrophilic species) with nitroethane or ammonium acetate. The reaction features mild con

Full text of DOI:10.1021/jo802318p

molecular electronics, opto-electronics, chemical sensing and
analysis, and photovoltaics because of their excellent photo-
physical properties.3 There are two general methods that have
been reported for the construction of teraryls. One is the
transition metal-catalyzed aryl-aryl coupling reactions of the
dihalobenzene derivatives with aryl nucleophiles (arylboronic
acids, arylmagnesium bromides, and arylstannyl halides etc.).4
The other is from diaryl-substituted open chain precursors to
build up the central phenyl ring, for example, via transition
metal-catalyzed [2 + 2 + 2] and [4 + 2] cycloadditions, which
has been extensively reviewed.5 For the former, the process is
primarily limited by the availability of the organometallic
coupling partners, and the incompatibility of the organometallic
partners with some certain electrophilic functional groups (e.g.,
carbonyls, enones).6 Although the latter approach is a common
and valuable protocol to polysubstituted benzene and teraryl
derivatives, the reaction often meets the problem of chemo- and
regioselectivity. Therefore, to match the increasing scientific
and practical demands, it is still of great importance to develop
simple and efficient approaches for the construction of teraryls,
especially those with flexible substitution patterns.
A New Route to Multifunctionalized p-Terphenyls
and Heteroaryl Analogues via [5C + 1C(N)]
Annulation Strategy
Lei Zhang, Fushun Liang,* Xin Cheng, and Qun Liu*
Department of Chemistry, Northeast Normal UniVersity,
Changchun 130024, China
liangfs112@nenu.edu.cn
ReceiVed October 12, 2008
On the other hand, the utility of R-oxo ketene-(S,S)-acetals
as versatile intermediates in organic synthesis has been recog-
nized.7 In our research on the chemistry of functionalized ketene-
(S,S)-acetals,8 easily available and structurally flexible R-alk-
enoyl ketene-(S,S)-acetals have been demonstrated as versatile
building blocks for the efficient construction of a wide variety
of six-membered carbo- and heterocycles including cyclohex-
enones (or phenols), 4-pyridones, and thiopyranones, on the
basis of [5C + 1C],9a [5C + 1N],9b,c and [5C + 1S]9d annulation
p-Terphenyls and heteroaryl analogues including bipyridines
were prepared via [5C + 1C(N)] annulation of R-aryl-R-
alkenoyl ketene-(S,S)-acetals (five carbon 1,5-bielectrophilic
species) with nitroethane or ammonium acetate. The reaction
features mild conditions, multisubstitution, and functional
group tolerance and is metal catalyst free. The present
protocol provides a new alternative to the conventional
methodologies for the synthesis of teraryls.
(3) (a) Mu¨llen, K.; Wegner, G. Electronic Materials: The Oligomer Approach;
Wiley-VCH: Weinhein, Germany, 1998. (b) Chen, B.; Baumeister, U.; Pelzl,
G.; Das, M. K.; Zeng, X.; Ungar, G.; Tschierske, C. J. Am. Chem. Soc. 2005,
127, 16578–16591. (c) Udayakumar, B. S.; Schuster, G. B. J. Org. Chem. 1992,
57, 348–352. (d) Kiryanov, A. A.; Sampson, P.; Seed, A. J. J. Mater. Chem.
2001, 11, 3068–3077. (e) Karastatiris, P.; Mikroyannidis, J. A.; Spiliopoulos,
I. K.; Fakis, M.; Persephonis, P. J. Polym. Sci. Part A: Polym. Chem. 2004, 42,
2214–2224. (f) Ogawa, H.; Ohnishi, K.; Shirota, Y. Synth. Met. 1997, 91, 243–
245. (g) Bordat, P.; Brown, R. Chem. Phys. Lett. 2000, 331, 439–445. (h) Fabian,
W. M. F.; Kauffman, J. M. J. Lumin. 1999, 85, 137–148. (i) Wright, R. S.;
Vinod, T. K. Tetrahedron Lett. 2003, 44, 7129–7132.
(4) For a review, see: (a) Hassan, J.; Se´vignon, M.; Gozzi, C.; Schulz, E.;
Lemaire, M. Chem. ReV. 2002, 102, 1359–1469. Selected examples on the
synthesis of symmetric and unsymmetric terphenyls, see: (b) Cho, C. H.; Kim,
I. S.; Park, K. Tetrahedron 2004, 60, 4589–4599. (c) Miguez, J. M. A.; Sousa-
Pedrares, L. A. A.; Vila, J. M.; Hii, K. K. J. Org. Chem. 2007, 72, 7771–7774.
(d) Todd, M. H.; Balasubramanian, S.; Abell, C. Tetrahedron Lett. 1997, 38,
6781–6784. (e) Corsico, E. F.; Rossi, R. A. Synlett 2000, 230–232. (f) Rottla¨nder,
M.; Knochel, P. J. Org. Chem. 1998, 63, 203–208. (g) Shimizu, H.; Manabe, K.
Tetrahedron Lett. 2006, 47, 5927–5931. (h) Child, A. D.; Reynolds, J. R.
Macromolecules 1994, 27, 1975–1977. (i) Goel, A.; Verma, D.; Singh, F. V.
Tetrahedron Lett. 2005, 46, 8487–8491. (j) Yamamoto, Y.; Nunokawa, K.; Ohno,
M.; Eguchi, S. Synthesis 1996, 8, 949–953. (k) Taylor, R. H.; Felpin, F.-X. Org.
Lett. 2007, 9, 2911–2914.
(5) Recent reviews on [2 + 2 + 2] and [4 + 2] cycloadditions, see: (a)
Saito, S.; Yamamoto, Y. Chem. ReV. 2000, 100, 2901–2915. (b) Kotha, S.;
Brahmachary, E.; Lahiri, K. Eur. J. Org. Chem. 2005, 474, 1–4767. (c)
Yamamoto, Y. Curr. Org. Chem. 2005, 9, 503–519. (d) Chopadea, P. R.; Louiea,
J. AdV. Synth. Catal. 2006, 348, 2307–2327. (e) Gandon, V.; Aubert, C.; Malacria,
M. Chem. Commun. 2006, 220, 9–2217. Selected papers on [2 + 2+2]
cycloaddition, see: (f) Shibata, T.; Fujimoto, T.; Yokota, K.; Takagi, K. J. Am.
Chem. Soc. 2004, 126, 8382–8383. (g) Tsuji, H.; Yamagata, K.; Fujimoto, T.;
Nakamura, E. J. Am. Chem. Soc. 2008, 130, 7792–7793. (h) McDonald, F. E.;
Smolentsev, V. Org. Lett. 2002, 4, 745–748.
p-Terphenyls have received considerable attention in the past
decades, due to their presence as a structural motif in natural
products, and their utility in biological and material sciences.1
Naturally isolated p-terphenyl derivatives including terphenyllin,
terferol, and terprenin have been reported to possess biological
activities with potential therapeutic values.2 Synthetic p-
terphenyls are often exploited in the material areas such as
(1) For a review on terphenyls, see: Liu, J.-K. Chem. ReV. 2006, 106, 2209-
2223.
(2) (a) Finkel, T.; Holbrook, N. J. Nature 2000, 408, 239. (b) Kamigauchi,
T.; Sakazaki, R.; Nagashima, K.; Kawamura, Y.; Yasuda, Y.; Matsushima, K.;
Tani, H.; Takahashi, Y.; Ishii, K.; Suzuki, R.; Koizumi, K.; Nakai, H.; Ikenishi,
Y.; Terui, Y. J. Antibiot. 1998, 51, 445. (c) Zhang, C.; Ondeyka, J. G.; Herath,
K. B.; Guan, Z.; Collado, J.; Pelaez, F.; Leavitt, P. S.; Gurnett, A.; Nare, B.;
Liberator, P.; Singh, S. B. J. Nat. Prod. 2006, 69, 710–712. (d) Roberti, M.;
Pizzirani, D.; Recanatini, M.; Simoni, D.; Grimaudo, S.; Di Cristina, A.;
Abbadessa, V.; Gebbia, N.; Tolomeo, M. J. Med. Chem. 2006, 49, 3012–3018.
(e) Simoni, D.; Giannini, G.; Roberti, M.; Rondanin, R.; Baruchello, R.; Rossi,
M.; Grisolia, G.; Invidiata, F. P.; Aiello, S.; Marino, S.; Cavallini, S.; Siniscalchi,
A.; Gebbia, N.; Crosta, L.; Grimaudo, S.; Abbadessa, V.; Di, Cristina, A.;
Tolomeo, M. J. Med. Chem. 2005, 48, 4293–4299. (f) Guo, H.; Hu, H.; Liu, S.;
Liu, X.; Zhou, Y.; Che, Y. J. Nat. Prod. 2007, 70, 1519–1521. (g) Ohkanda, J.;
Lockman, J. W.; Kothare, M. A.; Qian, Y.; Blaskovich, M. A.; Sebti, S. M.;
Hamilton, A. D. J. Med. Chem. 2002, 45, 177–188. (h) Sawayama, Y.; Tsujimoto,
T.; Sugino, K.; Nishikawa, K.; Isobe, M.; Kawagishi, H. Biosci. Biotechnol.
Biochem. 2006, 70, 2998–3003.
(6) (a) Baudoin, O. Angew. Chem., Int. Ed. 2007, 46, 1373–1375. (b) Frid,
M.; Pe´rez, D.; Peat, A. J.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 9469–
9470.
10.1021/jo802318p CCC: $40.75
Published on Web 11/26/2008
2009 American Chemical Society
J. Org. Chem. 2009, 74, 899–902 899

SCHEME 1
SCHEME 2. The Aldol Condensation of 1a,b with
Aldehydes
strategies, respectively (Scheme 1a).9 Our continued interest in
expanding the scope and potential applications of the formal [5
+ 1] annulation strategy prompted us to explore the feasibility
of construction of teraryls based on structurally modified R-aryl-
R-alkenoyl ketene-(S,S)-acetals (Scheme 1b). To this end,
R-phenyl-R-alkenoyl ketene-(S,S)-acetals were prepared and the
[5 + 1] annulation reaction with nitroethane as a carbon
nucleophile10 and ammonium acetate as a nitrogen nucleophile
were investigated, respectively. As a result, the teraryl frame-
works including p-terphenyls and heteroaromatic analogues were
successfully assembled via [5C + 1C(N)] annulation and
subsequent aromatization. Thus, a concise, efficient, and flexible
synthesis of unsymmetrical teraryls and analogues by this
protocol was developed. The [5C + 1C(N)] annulation strategy
employed here is versatile for both the phenyl- and pyridyl-
cored teraryls and heteroaryl analogues. Furthermore, no
problems of chemoselectivity and region-selectivity were in-
volved in the explored reaction. Herein, we wish to report our
experimental results.
The substrates 4,4-bis(ethylthio)-3-phenylbut-3-en-2-ones 1a
and 1b were prepared via either our reported procedure (for
1a) or the reaction of two molecules of 3-(bis(ethylthio)meth-
ylene)pentane-2,4-dione with NaOH as the base (for 1b).11 The
condensation products 2 were prepared in 91-96% yields by
treatment of 1 with a variety of aromatic aldehydes (Scheme
2), and were used directly without further purification.
With the easily available substrates 2 in hand, we started the
[5C + 1C(N)] annulation reaction toward the synthesis of teraryl
compounds. The [5C + 1C] reaction of 2 and nitroethane was
examined first. A model reaction of 2a1 (1.0 mmol) and
nitroethane (1.2 mmol) with DBU (4.0 mmol) as the base was
carried out in DMF (10 mL) as reported previously in our
group.9 However, no reaction occurred when the mixture was
stirred at either room temperature or heated to 70 °C. In view
of the different structure and thus different reactivity between
R-aryl-R-alkenoyl ketene-(S,S)-acetals 2 and R-EWG-R-alkenoyl
counterpart utilized before (as shown in Scheme 1), the reaction
was further explored under elevated temperature. To our delight,
when the mixture was stirred at 120 °C for 6.0 h, the above
reaction proceeded smoothly and gave rise to the desired
p-terphenyl compound 3a1 in 83% yield. Under the optimized
conditions described above, a range of reactions between
R-substituted phenyl-R-alkenoyl ketene-(S,S)-acetals 2a2-6 (1.0
mmol) and nitroethane (1.2 mmol) were carried out at 120 °C
in DMF (10 mL), furnishing teraryls 3a2-6 in yields of
78-88% (Table 1, entries 2-6). Similarly, the reactions of
substrates 2b with nitroethane also gave satisfactory results
(Table 1, entries 7-12). Compounds 3b1-7 were obtained in
good to high yields (71-87%). In the teraryl or terheteroaryl
products 3a1-6 and 3b1-7, the Ar group varied from aryl
(phenyl, 4-chlorophenyl, 4-methoxyphenyl, 3-nitrophenyl) to
heteroaryl (2-furyl, 2-thienyl, or 2-pyridyl). The heteroaryl
anologues of p-terphenyls also represent an important class of
organic molecules for their useful bio-, physio-, and pharma-
cological activities, as well as their application as organic
materials.3 One of the notable features of the teraryls and
analogues 3 synthesized here is the multiple substituents and
functional groups incorporated on the backbones (hydroxy,
methyl, methoxy, ethoxy, ethylthio, acetyl, etc.), which provides
the structural diversity of the unsymmetric teraryls and a
potential for further modification. In addition, the mono- or
diphenolic terphenyl frameworks have been found to exist
widely in natural isolated terphenyl products.1,2 Therefore, the
present protocol gives a straightforward and general pathway
to construct highly substituted teraryls and analogues of type 3
without the use of metal catalysts.
Pyridine is one of the most important nitrogen heterocycles,
playing a key role in several biological processes.12 Thus, the
[5C + 1N] annulation reaction of 2 was investigated to construct
teraryls with a central pyridine ring.13 Initially, we focused on
the synthesis of bipyridines, considering that it may act as a
chelating ligand that forms complexes with most transition metal
ions.14 Thus, the mixture of 2a7 or 2b7 (Ar ) 2-pyridyl) and
(7) For reviews on the synthesis and application of R-oxo ketene-(S,S)-acetals,
see: (a) Dieter, R. K. Tetrahedron 1986, 42, 3029–3096. (b) Tominaga, Y.
J. Heterocycl. Chem. 1989, 26, 1167–1204. (c) Junjappa, H.; Ila, H.; Asokan,
C. V. Tetrahedron 1990, 46, 5423–5506. (d) Kolb, M. Synthesis 1990, 171–
190. (e) Junjappa, H.; Ila, H. Phosphorus, Sulfur Silicon 1994, 35, 95–96. (f)
Junjappa, H.; Ila, H.; Mohanta, P. K. In Progress in Heterocyclic Chemistry;
Gribble, G. H., Gilchrist, L. T., Eds.; Pergamon Press: Oxford, UK, 2001; Vol.
13,Chapter 1, pp 1-24.
(8) (a) Liang, F.; Zhang, J.; Tan, J.; Liu, Q. AdV. Synth. Catal. 2006, 348,
1986–1990. (b) Liang, F.; Li, D.; Zhang, L.; Gao, J.; Liu, Q. Org. Lett. 2007, 9,
4845–4848. (c) Kang, J.; Liang, F.; Sun, S.; Liu, Q.; Bi, X. Org. Lett. 2006, 8,
2547–2550. (d) Li, Y.; Liang, F.; Bi, X.; Liu, Q. J. Org. Chem. 2006, 71, 8006–
8010. (e) Liang, F.; Li, Y.; Li, D.; Cheng, X.; Liu, Q. Tetrahedron Lett. 2007,
48, 7938–7941.
(9) [5 + 1] annulation: (a) Bi, X.; Dong, D.; Liu, Q.; Pan, W.; Zhao, L.; Li,
B. J. Am. Chem. Soc. 2005, 127, 4578–4579. (b) Dong, D.; Bi, X.; Liu, Q.;
Cong, F. Chem. Commun. 2005, 3580–3582. (c) Zhao, L.; Liang, F.; Bi, X.;
Sun, S.; Liu, Q. J. Org. Chem. 2006, 71, 1094–1098. (d) Bi, X.; Dong, D.; Li,
Y.; Liu, Q. J. Org. Chem. 2005, 70, 10886–10889.
(10) For a recent review on nitroalkanes for the synthesis of benzene
derivatives, see: Ballini, R.; Palmieri, A.; Barboni, L. Chem. Commun. 2008,
2975–2985.
(12) For a thorough review of the history, applications, and synthesis of
pyridine derivatives, see: Henry, G. D. Tetrahedron 2004, 60, 6043–6061.
(13) For reviews on the construction of pyridine rings from cycloaddition,
see: (a) Varela, J. A.; Saa´, C. Chem. ReV. 2003, 103, 3787–3801. (b) Heller, B.;
Hapke, M. Chem. Soc. ReV., 2007, 36, 1085–1094. For the transition metal-
catalyzed synthesis of poly-substituted pyridines, see: (c) McCormick, M. M.;
Duong, H. A.; Zuo, G.; Louie, J. J. Am. Chem. Soc. 2005, 127, 5030–5031. (d)
Heller, B.; Sundermann, B.; Fischer, C.; You, J.; Chen, W.; Drexler, H. J.;
Knochel, P.; Bonrath, W.; Gutnov, A. J. Org. Chem. 2003, 68, 9221–9225. (e)
Tanaka, R.; Yuza, A.; Watai, Y.; Suzuki, D.; Takayama, Y.; Sato, F.; Urabe, H.
J. Am. Chem. Soc. 2005, 127, 7774–7780. (f) Heller, B.; Sundermann, B.;
Buschmann, H.; Drexler, H. J.; You, J.; Holzgrabe, U.; Heller, E.; Oehme, G. J.
Org. Chem. 2002, 67, 4414–4422. (g) Young, D. D.; Deiters, A. Angew. Chem.,
Int. Ed. 2007, 46, 5187–5190. (h) Chang, H.-T.; Jeganmohan, M.; Cheng, C.-H.
Org. Lett. 2007, 9, 505–508.
(11) For synthetic details, please see the Supporting Information.
(14) Constable, E. C. AdV. Inorg. Chem. 1989, 34, 1–63.
900 J. Org. Chem. Vol. 74, No. 2, 2009

TABLE 1. Synthesis of p-Terphenyls and Their Heteroaryl
Analogues Using [5C + 1C] Annulation
SCHEME 3. Synthesis of Multisubstituted Bipyridines
Based on [5C + 1N] Annulation
excess NH4OAc (ammonia source,15 8.0 equiv) was stirred in
DMSO at 120 °C for 10 h. Gratifyingly, 2,2′-bipyridines 4a
and 4b were prepared by the one-pot procedure (Scheme 3),
although the yields (44% for 4a and 47% for 4b) were
incomparable to that of the teraryls produced by [5C + 1C]
annulation (Table 1); it was noteworthy that the central pyridyl
rings in compounds 4 could be formed via [5C + 1N] annulation
and subsequent aromatization in formal dehydrogenation, most
probably by air oxidation), while in our previous work on [5C
+ 1N] annulation reaction, the aza-cyclization products were
demonstrated as pyridone derivatives, which could not further
aromatize to give the pyridines.9c Similar dehydrogenation has
been observed in our recent work16a and that reported by Xue
et al.16b Clearly, 5-arylayed bipyridyls of type 4 may be con-
structed by the [5C + 1N] annulation protocol. In the following
work to construct teraryls containing a central pyridine ring with
other substrates like 2a1, 2a4, 2b1, and 2b4, however, the
reactions were proved to be inefficient under otherwise identical
conditions. It seems that the reactivity of 2 with various
substrates is different and plays an important role in the [5C +
1N] annulation reaction.
In the reaction of substrate 2b with nitroethane (Table 1, entry
7), a Michael adduct 5 was isolated in 53% yield by quenching
the reaction within 3.0 h (Figure 1). On the basis of all above
results, as well as our previous work,9 a possible mechanism
for the annulation of 2 with C/N nucleophiles is proposed, as
depicted in Scheme 4. The tandem reaction led to teraryls and
analogues involves Michael addition, intramolecular cyclization
(addition-elimination), and aromatization sequences.
In summary, we have developed an efficient method for the
synthesis of highly functionalized p-terphenyls and heteroaryl
analogues using the [5C + 1C(N)] annulation reaction of R-aryl-
R-alkenoyl ketene-(S,S)-acetal with carbon or nitrogen nucleo-
philes, which provides a new alternative route to the conven-
tional metal-catalyzed methodologies. The reaction features mild
conditions, multisubstitution, and functional group tolerance and
is metal catalyst-free. Further work to construct diversely
polysubstituted pyridines, bipyridines, and terpyridines is un-
derway in our laboratory.
(15) Examples for the synthesis of pyridine derivatives using ammonium
acetate as the nitrogen source, see:(a) Ladouceur, G. H.; Cook, J. H.; Doherty,
E. M.; Schoen, W. R.; MacDougall, M. L.; Livingston, J. N. Bioorg. Med. Chem.
Lett. 2002, 12, 461–464. (b) Rodriguez, H.; Suarez, M.; Perez, R.; Petit, A.;
Loupy, A. Tetrahedron Lett. 2003, 44, 3709–3712. (c) Bowman, M. D.; Jacobson,
M. M.; Pujanauski, B. G.; Blackwell, H. E. Tetrahedron 2006, 62, 4715–4727.
(16) Selected examples of aromatization via dehydrogenation, see: (a) Hu,
J.; Zhang, Q.; Yuan, H.; Liu, Q. J. Org. Chem. 2008, 73, 2442–2445. (b) Xue,
D.; Li, J.; Zhang, Z.-T.; Deng, J.-G. J. Org. Chem. 2007, 72, 5443–5445.
a Reagents and conditions: 2 (1.0 mmol), EtNO2 (1.2 mmol), DBU
(4.0 mmol), DMF (10 mL), 120 °C, 6.0-8.0 h. b Isolated yield.
J. Org. Chem. Vol. 74, No. 2, 2009 901

6.90 (s, 1H), 7.06 (d, J ) 8.5 Hz, 2H), 7.30 (d, J ) 8.5 Hz, 2H),
7.31-7.38 (m, 3H), 7.43 (d, J ) 8.0 Hz, 2H). 13C NMR (DMSO-
d6, 125 MHz) δ 14.7, 19.4, 29.6, 55.3, 113.8, 114.5, 117.0, 127.0,
127.9, 128.2, 129.2, 131.88, 132.0, 134.8, 142.3, 143.4, 151.0,
159.4. Anal. Calcd for C22H22O2S: C, 75.39; H, 6.33. Found: C,
75.40; H, 6.30.
General Procedure for the Preparation of 4 (4a as an
example). To a solution of 1,1-bis(ethylthio)-2-(4-methoxyphenyl)-
5-(pyridin-2-yl)penta-1,4-dien-3-one (2a7, 386 mg, 1.0 mmol) in
DMSO (5 mL) was added NH4OAc (616 mg, 8 mmol). The reaction
mixture was heated to 100 °C for 10 h, then the resulting mixture
was allowed to cool to room temperature. Next the reaction mixture
was extracted with CH2Cl2 (3 × 10 mL). The combined organic
phase was washed with water (3 × 20 mL), dried over MgSO4,
filtered, and concentrated in vacuo. The crude product was purified
by flash chromatography (silica gel, petroleum ether:diethyl ether
) 1:2) to give 4a (149 mg, 44%) as a yellow solid.
FIGURE 1. Structure of compound 5.
SCHEME 4. Proposed Mechanism for the Formation of
Teraryls and Their Derivatives
6-(Ethylthio)-5-(4-methoxyphenyl)-2,2′-bipyridin-4-ol (4a):
1
mp 114-116 °C. H NMR (CDCl3, 500 MHz) δ 1.38 (t, J ) 7.5
Hz, 3H), 3.20-3.24 (m, 2H), 3.87 (s, 3H), 4.00 (s, 1H), 7.04 (d, J
) 8.5 Hz, 2H), 7.28 (d, J ) 8.0 Hz, 2H), 7.32 (s, 1H), 7.57 (s,
1H), 7.81 (t, J ) 8.0 Hz, 1H), 8.46 (d, J ) 7.5 Hz, 1H), 8.64 (d,
J ) 4.0 Hz, 1H). 13C NMR (DMSO-d6, 125 MHz) δ 14.9, 29.9,
55.5, 103.9, 115.1, 119.6, 121.2, 123.7, 126.4, 131.8, 137.0, 149.1,
151.3, 154.3, 156.6, 158.1, 159.9. IR (KBr, cm-1) 686, 788, 1174,
1241, 1289, 1401, 1449, 1508, 1550, 1575, 1641, 2854, 2923, 2955.
MS calcd m/z 338.4, found 339.5 [(M + 1)]+. Anal. Calcd for
C19H18N2O2S: C, 67.43; H, 5.36; N, 8.28. Found: C, 67.45; H, 5.38;
N, 8.30.
Experimental Section
General Procedure for Preparation of 3 (3a1 as an example).
To a solution of 1,1-bis(ethylthio)-2-(4-methoxyphenyl)-5-phenyl-
penta-1,4-dien-3-one (2a1, 385 mg, 1.0 mmol) in DMF (10 mL)
was added DBU (0.32 mL, 4.0 mmol) and nitroethane (0.17 mL,
1.2 mmol). The reaction mixture was heated to 120 °C for 6 h.
After the starting material 2a1 was consumed as indicated by TLC,
the resulting mixture was allowed to cool to room temperature.
Then the reaction mixture was extracted with CH2Cl2 (3 × 10 mL).
The combined organic phase was washed with water (3 × 20 mL),
dried over MgSO4, filtered, and concentrated in vacuo. The crude
product was purified by flash chromatography (silica gel, petroleum
ether:diethyl ether ) 4:1) to give 3a1 (290 mg, 83%) as a yellow
solid.
Acknowledgment. Financial support of this research by
NENU-STB07007 and the Department of Science and Technol-
ogy of Jilin Province (20080421) is greatly acknowledged.
Supporting Information Available: Experimental details and
characterization data for 1-5. This material is available free of
charge via the Internet at http://pubs.acs.org.
4-Methoxy-6′-(ethylthio)-5′-methyl-p-terphenyl-2′-ol (3a1): mp
1
124-126 °C. H NMR (CDCl3, 500 MHz) δ 1.04 (t, J ) 7.5 Hz,
3H), 2.41 (s, 3H), 2.43-2.46 (m, 2H), 3.89 (s, 3H), 4.77 (s, 1H),
JO802318P
902 J. Org. Chem. Vol. 74, No. 2, 2009