Microwave-assisted copper-catalyzed preparation of diaryl chalcogenides

Article abstract of DOI:10.1021/jo060690a

Diaryl chalcogenide synthesis employing diaryl dichalcogenides and aryl halides as starting materials in the presence of excess magnesium and a catalytic amount of CuI/bipyridyl is significantly improved by microwave heating. Reaction times can be reduced from 2 to 3 days to 6-8 h. Both aryl bromides and aryl chlorides can be used as substrates in the substitution reaction. The procedure is useful not only for diaryl sulfide and diaryl selenide synthesis but also for the preparation of unsymmetrical diaryl tellurides. Starting from suitable aryl halides, the novel microwave-assisted procedure was used for the facile preparation of novel chalcogen analogues (PhS-, PhSe-, and PhTe-) of various antioxidants (ethoxyquin and 3-pyridinol). Attempts to use dialkyl dichalcogenides for the coupling of alkylchalcogeno moieties to aryl halides were only successful in the case of long-chain (such as n-octyl) disulfides and diselenides.

Full text of DOI:10.1021/jo060690a

evaluating the effect of the chalcogen in a structure selected, it
is desirable to have easy access to all three arylchalcogenide
analogues4 (sulfide, selenide, and telluride) starting from a
common precursor. Out of the many methods available for aryl-
chalcogen bond-formation, we thought the coupling of aryl
halides with thiolates, selenolates, and tellurolates would be
ideally suited for our purposes. However, unless the substitution
reaction is catalyzed or otherwise facilitated (e.g., by photolysis,5
electrolysis,6 metal-promoted electron transfer,7 or by formation
of a transition metal arene complex of the aryl halide8),
nucleophilic substitution can only be effected under forcing
conditions. Already in the 1980s, Migita and Cristau reported
Pd- and Ni-catalyzed cross-coupling of aryl bromides and
iodides with thiolates and selenolates.9 Although yields were
generally satisfying, long reaction times at elevated temperature
were often required for nonactivated aryl halides. More recently,
Itoh and Hartwig10 have reported improved palladium-based
catalyst systems for coupling of aryl halides and triflates with
thiols. For diaryl selenide synthesis, phenyl tributylstannyl
selenide, PhSeSnBu3, was found to function as an excellent
partner in the Pd- or Ni-catalyzed reaction with aryl halides
and triflates.11 Copper-based catalyst systems have proven
effective for the cross-coupling of aryl iodides with both thiols
and selenols.12 Methodology for diaryl telluride synthesis by
Microwave-Assisted Copper-Catalyzed
Preparation of Diaryl Chalcogenides
Sangit Kumar and Lars Engman*
Department of Biochemistry and Organic Chemistry, Box 576,
SE-751 23 Uppsala, Sweden
lars.engman@kemi.uu.se
ReceiVed March 31, 2006
Diaryl chalcogenide synthesis employing diaryl dichalco-
genides and aryl halides as starting materials in the presence
of excess magnesium and a catalytic amount of CuI/bipyridyl
is significantly improved by microwave heating. Reaction
times can be reduced from 2 to 3 days to 6-8 h. Both aryl
bromides and aryl chlorides can be used as substrates in the
substitution reaction. The procedure is useful not only for
diaryl sulfide and diaryl selenide synthesis but also for the
preparation of unsymmetrical diaryl tellurides. Starting from
suitable aryl halides, the novel microwave-assisted procedure
was used for the facile preparation of novel chalcogen
analogues (PhS-, PhSe-, and PhTe-) of various antioxidants
(ethoxyquin and 3-pyridinol). Attempts to use dialkyl dichal-
cogenides for the coupling of alkylchalcogeno moieties to
aryl halides were only successful in the case of long-chain
(such as n-octyl) disulfides and diselenides.
(2) (a) Okamoto, Y., in Patai, S., Rappoport, Z., Eds. The Chemistry of
Organic Selenium and Tellurium Compounds; Wiley: Chichester, U.K.,
1986; Vol. 1, Chapter 10. (b) Hellberg, J.; Remonen, T.; Johansson, M.;
Ingana¨s, O.; Theander, M.; Engman, L.; Eriksson, P. Synth. Met. 1997, 84,
251. (c) Ando, T.; Kwon, T. S.; Kitagawa, A.; Tanemura, T.; Kondo, S.;
Kunisada, H.; Yuki, Y. Macromol. Chem. Phys. 1996, 197, 2803. (d) Takagi,
K.; Nishikawa, Y.; Kwon, T. S.; Kunisada, H.; Yuki, Y. Polym. J. 2000,
32, 970. (e) Stuhr-Hansen, N.; Beckers, E. H. A.; Engman, L.; Janssen, R.
A. J. Heteroat. Chem. 2005, 16, 656.
(3) (a) Andersson, C.-M.; Hallberg, A.; Brattsand, R.; Cotgreave, I. A.;
Engman, L.; Persson, J. Bioorg. Med. Chem. Lett. 1993, 3, 2553. (b)
Engman, L.; Stern, D.; Pelcman, M.; Andersson, C-M. J. Org. Chem. 1994,
59, 1973. (c) Vessman, K.; Ekstro¨m, M.; Berglund, M.; Andersson, C.-M.;
Engman L. J. Org. Chem. 1995, 60, 4461. (d) Kanda, T.; Engman, L.;
Cotgreave, I. A.; Powis, G. J. Org. Chem. 1999, 64, 8161. (e) McNaughton,
M.; Engman, L.; Birmingham, A.; Powis, G., Cotgreave, I. A. J. Med. Chem.
2004, 47, 233. (f) Shanks, D.; Amorati, R.; Fumo, M. G.; Pedulli, G. F.;
Valgimigli, L.; Engman, L. J. Org. Chem. 2006, 71, 1033.
(4) (a) Engman, L.; Stern, D.; Frisell, H.; Vessman, K.; Berglund, M.;
Ek, B.; Andersson, C.-M. Bioorg. Med. Chem. 1995, 3, 1255. (b)
Malmstro¨m, J.; Jonsson, M.; Cotgreave, I. A.; Hammarstro¨m, L.; Sjo¨din,
M.; Engman, L. J. Am. Chem. Soc. 2001, 123, 3434. (c) Shanks, D.; Al-
Maharik, N.; Malmstro¨m, J.; Engman, L.; Eriksson, P.; Stenberg, B.;
Reitberger, T. Polym. Degrad. Stab. 2003, 81, 261.
Introduction
Aryl chalcogenide structural motifs are commonly found in
a variety of molecules of biological/pharmaceutical1 and materi-
als2 interest. We study the antioxidative properties3 of organo-
sulfur, organoselenium, and organotellurium compounds with
the perspective to find compounds which could act in a catalytic
fashion to decompose both hydroperoxides (peroxide decompos-
ing antioxidants) and peroxyl radicals (chain-breaking donating
antioxidants). Because of their stability also at elevated tem-
peratures, aryl chalcogenides are often our target molecules. For
(5) Pierini, A. B.; Pene´nory, A. B.; Rossi, R. A. J. Org. Chem. 1984,
49, 486.
(6) Degrand, C.; Prest, R. J. Org. Chem. 1987, 52, 5229.
(7) Zhang, Y.; Guo, H. Heteroat. Chem. 2001, 12, 539.
(8) (a) Vasil’ev, A. A.; Engman, L.; Storm, J. P.; Anderson, C.-M.
Organometallics 1999, 18, 1318. (b) Smirnova, J.; Engman, L.; Andersson,
C.-M.; Malm, J. J. Organomet. Chem. 2005, 690, 1784 and references cited
therein.
(9) (a) Migita, T.; Shimizu, T.; Shiobara, J.; Kato, Y.; Kosugi, M. Bull.
Chem. Soc. Jpn. 1980, 53, 1385. (b) Cristau, H. J.; Chabaud, B.; Christol,
C. H. Synthesis 1981, 892. (c) Cristau, H. J.; Chabaud, B.; Labaudiniere,
R.; Christol, H. 1985, 4, 657.
(10) (a) Itoh, T.; Mase, T. Org. Lett. 2004, 6, 4587. (b) Ferna´ndez-
Rodriges, M. A.; Shen, Q.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128,
2180.
(11) (a) Nishiyama, Y.; Tokunaga, K.; Sonoda, N. Org. Lett. 1999, 1,
1725. (b) Beletskaya, I. P.; Sigeev, A. S.; Peregudov, A. S.; Petrovskii, P.
V. J. Organomet. Chem. 2000, 605, 96. (c) Beletskaya, I. P.; Sigeev, A. S.;
Peregudov, A. S.; Petrovskii, P. V. Russ. J. Org. Chem. 2001, 37, 1463.
(d) Beletskaya, I. P.; Sigeev, A. S.; Peregudov, A. S.; Petrovskii, P. V.
Tetrahedron Lett. 2003, 44, 7039.
(1) See for example the following: (a) Kaldor, S. W.; Kalish, V. J.;
Davies II, J. F.; Shetty, B. V.; Fritz, J. E.; Appelt, K.; Burgess, J. A.;
Campanale, K. M.; Chirgadze, N. Y.; Clawson, D. K.; Dressman, B. A.;
Hatch, S. D.; Khalil, D. A.; Kosa, M. B.; Lubbehusen, P. P.; Muesing, M.
A.; Patick, A. K.; Reich, S. H.; Su, K. S.; Tatlock, J. H. J. Med. Chem.
1997, 40, 3979. (b) Liu, G.; Huth, J. R.; Olejniczak, E. T.; Mendoza, R.;
DeVries, P.; Leitza, S.; Reilly, E. B.; Okasinski, G. F.; Fesik, S. W.; von
Geldern, T. W. J. Med. Chem. 2001, 44, 1202. (c) Liu, L.; Stelmach, J. E.;
Natarajan, S. R.; Chen, M.-H.; Singh, S. B.; Schwartz, C. D.; Fitzgerald,
C. E.; O’Keefe, S. J.; Zaller, D. M.; Schmatz, D. M.; Doherty, J. B. Bioorg.
Med. Chem. Lett. 2003, 13, 3979. (d) Parnham, M. J.; Graf, E. Prog. Drug
Res. 1991, 36, 9. (e) Goudgaon, N. M.; Naguib, F. N. M.; el Kouni, M. H.;
Schinazi, F. J. Med. Chem. 1993, 36, 4250. (f) Mugesh, G.; du Mont, W.-
W.; Sies, H. Chem. ReV. 2001, 101, 2125. (g) Zhang, S.-J.; Dong, J.-Q.;
Wang, Y.-G. Synth. Commun. 2003, 33, 1891.
10.1021/jo060690a CCC: $33.50 © 2006 American Chemical Society
Published on Web 06/17/2006
5400
J. Org. Chem. 2006, 71, 5400-5403

TABLE 1. Preparation of Diphenyl Chalcogenides from Diphenyl
Dichalcogenides and Halobenzenes
the substitution of unactivated aryl halides with arenetellurolate
is scarce.13 However, both diaryl ditellurides and diaryl dis-
elenides were recently found to produce the corresponding
unsymmetrical diaryl chalcogenides when reacted in DMSO at
100 °C with arylboronic acids in the presence of a catalytic
amount of copper(I)-iodide.14
a
Ph-Y + 1/2PhXXPh CuI/bipyridyl 8 Ph-X-Ph
Mg, DMF
microwaves
reaction time
(h)
temperature
product
(% yield)b
Arenethiolates, selenolates, and tellurolates are all only
weakly basic, and basicity would rarely be a problem during
their introduction into more complex organic molecules by
aromatic nucleophilic substitution. However, the sensitivity of
the chalcogenide species toward oxidation is more troublesome.
This is especially true for arenetellurolates which are converted
to the corresponding ditellurides unless air is rigorously
excluded. Therefore, it was interesting that Taniguchi could use
both arylchalcogeno moieties of easy to handle diaryl disulfides
and diaryl diselenides for diaryl chalcogenide synthesis by
heating in DMF for 1 to 3 days with aryl iodides in the presence
of catalytic amounts of a copper catalyst, 2,2′-bipyridyl and
excess magnesium metal (eq 1).15 We were curious to see if
this methodology could be extended also to diaryl telluride
synthesis and if the slow cross-coupling reaction could be
accelerated and induced to occur also with the much less
reactive, but more readily available, aryl bromides and chlorides.
Y
X
(°C)
Cl
Br
I
Cl
Br
I
Cl
Br
I
Te
Te
Te
Se
Se
Se
S
6
6
6
6
6
6
6
6
6
200
160
160
200
200
200
200
200
200
Ph2Te (40)
Ph2Te (65)
Ph2Te (60)
Ph2Se (48)
Ph2Se (60)
Ph2Se (62)
Ph2S (58)
Ph2S (64)
Ph2S (60)
S
S
a An amount of 10, 15, and 20 mol-%, respectively, for diphenyl telluride,
diphenyl selenide and diphenyl sulfide synthesis. b Isolated yield.
genides under similar conditions using iodobenzene as a starting
material turned out to be in the same range (60-62%). Out of
the three diphenyl chalcogenides, the telluride was the most
readily prepared (usually at 160 °C using 10 mol-% of
catalyst18). For preparation of the selenide and sulfide, heating
at 200 °C in the presence of 15 and 20 mol-%, respectively, of
catalyst was required. It is noteworthy that ordinary magnesium
turnings could be used in these experiments instead of magne-
sium powder.15
Cu(l)bipyridyl (10%)
Ar′-I + 1/2ArXXAr
8 Ar′-X-Ar
Mg, DMF, 110 °C
X ) S, Se (1)
By using the conditions in Table 1, we next turned to explore
the generality of the substitution reaction for diaryl chalcogenide
synthesis and the possibility to prepare aryl alkyl chalcogenides
by a similar protocol using dialkyl dichalcogenides as starting
materials. In Table 2 it is shown that phenylchalcogeno groups
could be coupled to both haloaromatics and haloheteroaromatics
(4-bromotoluene, 1-bromonaphthalene, 4-chloro- and 4-bro-
mophenol, N,N-dimethyl-4-bromoaniline, and 3-bromopyridine)
containing various functional groups in fair to good yields (42-
90%). However, attempted coupling with 4-bromoanisole
produced a complex mixture of products where the O-methyl
group was no longer present. We speculate that copper(I)-
phenylchalcogenenolate under the harsh reaction conditions is
causing demethylation by nucleophilic attack at the methyl. This
type of reactivity was not a problem when 4-iodoanisole was
used as a starting material and the reaction subjected to ordinary
heating at 110 °C in DMF.15 To show that the microwave-
assisted reaction is not restricted to the coupling of diphenyl
dichalcogenides with haloaromatics, di-1-naphthyl ditelluride,
di-1-naphthyl diselenide, and di-1-naphthyl disulfide were
reacted with bromobenzene under the usual catalyzed conditions
to provide compounds 2a-c in an alternative way (55, 68, and
78% yields, respectively; for structures see Table 2). Some
attempts were also made to introduce more than one arylchal-
cogeno group into polyhalogenated aromatics. However, when
1,4-dibromobenzene was subjected to microwave-assisted, cop-
per-catalyzed substitution using a stoichiometric amount of
diphenyl diselenide, only the monosubstitution product 6 was
In the following, we report an improved, microwave-assisted
method for diaryl chalcogenide synthesis which significantly
widens the scope of the coupling reaction shown in eq 1.
Results and Discussion
Microwave dielectric heating causes an extremely rapid and
uniform energy transfer to the reactants of chemical reactions.16
This will minimize byproduct formation and increase product
yields. In pressurized systems, it is also possible to use
temperatures far above the boiling point of the solvent. We
therefore thought it would be interesting to study the effect of
microwave heating on the reaction of aryl halides with diaryl
dichalcogenides in the presence of a copper(I)-catalyst, 2,2′-
bipyridyl, and magnesium. Initially, to find proper reaction
conditions, diphenyl ditelluride, diphenyl diselenide, or diphenyl
disulfide was allowed to react with either chloro- or bromoben-
zene at various temperatures in solvents suitable for microwave
heating (THF, NMP, or DMF). It was indeed possible to
successfully perform all the coupling reactions attempted, but
temperatures in the range of 160-200 °C and reaction times in
the order of 6 to 7 h were required for complete conversion of
the starting materials (Table 1). Under the best conditions found
(DMF as a solvent; 10-20% of CuI as a catalyst17), moderate
to good (40-65%) yields of diphenyl chalcogenides could be
obtained (Table 1). Isolated yields of the three diaryl chalco-
(12) (a) Bates, C. G.; Gujadhur, R. K.; Venkataraman, D. Org. Lett. 2002,
4, 2803. (b) Kwong, F. Y.; Buchwald, S. L. Org. Lett. 2002, 4, 3517. (c)
Gujadhur, R. K.; Venkataraman, D. Tetrahedron Lett. 2003, 44, 81.
(13) Irgolic, K. J. Ed. Houben-Weyl. Methods of Organic Chemistry;
Thieme: Stuttgart, Germany, 1990; Vol. E 12B, p 409.
(14) Wang, L.; Wang, M.; Huang, F. Synlett 2005, 2007.
(15) (a) Taniguchi, N.; Onami, T. Synlett 2003, 829. (b) Taniguchi, N.;
Onami, T. J. Org. Chem. 2004, 69, 915.
(16) Kappe, O. Angew. Chem., Int. Ed. 2004, 43, 6250.
(17) It was found that Cu2O was a much poorer catalyst than CuI in
these coupling reactions.
formed (55% yield). To see if the microwave-assisted reaction
would be suitable for the coupling of alkylchalcogeno groups
J. Org. Chem, Vol. 71, No. 14, 2006 5401

TABLE 2. Preparation of Aryl Phenyl Chalcogenides from
Haloaromatics and Diphenyl Dichalcogenides
and multifunctional (chain-breaking and peroxide decomposing)
antioxidants, we were interested in the synthesis of ethoxyquin
analogues carrying phenylchalcogeno groups in the 6-position
of the dihydroquinoline backbone. The corresponding bromide,
8b, is readily available by condensation of 4-bromoaniline with
2 equiv of acetone. We were pleased to find that the microwave-
assisted copper-catalyzed methodology developed was well
suited for preparation of the desired organochalcogen antioxi-
dants. Thus, under the standard conditions for coupling,
compounds 8c, 8d, and 8e were obtained in 32, 63, and 70%
yield, respectively.
a
Ar-Y + 1/2PhXXPh CuI/bipyridyl 8 Ar-X-Ph
Mg, DMF
microwaves
Electron-rich 3-pyridinols have recently been introduced as
new antioxidant scaffolds. Thus, compounds such as 9 are the
fastest chain-breaking antioxidants ever reported.20 We were
curious to see if introduction of arylchalcogeno groups into this
class of compounds would improve the antioxidant capacity
even further, for example, by imposing a peroxide decomposing
capacity and a catalytic mode of action in the presence of a
suitable stoichiometric reducing agent. As a model compound,
we therefore subjected the commercially available iodopyridinol
10a to the usual conditions for microwave-assisted introduction
of phenylchalcogeno groups. Although the yield of the tellurium
compound was only modest (compounds 10b, 10c, and 10d
were obtained in 30, 63, and 70% yields, respectively) all
chalcogen derivatives could be readily prepared. The novel
organochalcogen antioxidants 8 and 10 are presently being
evaluated in our laboratories.
In summary, we have shown that the CuI-catalyzed coupling
of arylchalcogeno-moieties to aryl halides is significantly
improved by microwave heating. Thus, reaction times can be
reduced from 2 to 3 days to 6-8 h. Both aryl bromides and
aryl chlorides can be used as substrates in the substitution
reaction. The procedure is useful not only for diaryl sulfide and
diaryl selenide synthesis but also for the preparation of diaryl
tellurides. The usefulness of the microwave-procedure was
demonstrated in the preparation of novel chalcogen containing
antioxidants (ethoxyquins and 3-pyridinols).
a 10, 15, and 20 mol-%, respectively, for telluride, selenide and sulfide
synthesis. b isolated yield.
to aryl bromides, 4-bromophenol was allowed to react with di-n-
propyl disulfide and di-n-butyl diselenide, respectively, under the
usual catalyzed conditions. Although the desired substitution pro-
ducts were formed, most of the bromophenol remained unre-
acted. Surprisingly, conversion was much better when di-n-octyl
disulfide or di-n-octyl diselenide were employed as dichalco-
genide starting materials. Thus, compounds 7a and 7b were iso-
lated in 79 and 94% yields, respectively. Attempts to use di-n-
octyl ditelluride for coupling an octyltelluro moiety to 4-bromo-
phenol and other haloaromatics were met with failure. Dehalogen-
ation seems to become a major competing process in these reac-
tions. Thus, naphthalene was isolated in 42% yield when 1-bromo-
naphthalene was used as a substrate. In a control experiment in
the absence of ditelluride, the bromonaphthalene was recovered.
Ethoxyquin (8a) possesses remarkable antioxidant capacity.19
It is used as an antioxidant in fish meal and animal feed and as
an additive to rubber. With the perspective to obtain catalytic
Experimental Section
Typical Procedure for Microwave-Assisted Synthesis of
Diaryl Chalcogenides. 4-Hydroxyphenyl Phenyl Selenide (3b).
4-Bromophenol (519 mg, 3.0 mmol) and diphenyl diselenide (469
mg, 1.5 mmol) were added to a stirred mixture of CuI (86 mg,
0.45 mmol), Mg turnings (144 mg, 6.0 mmol), and 2,2-bipyridyl
(bpy) (69 mg, 0.45 mmol) in DMF (5 mL). This reaction mixture
was heated at 200 °C in a sealed tube in a microwave reactor (300
W) for 7 h. The reaction mixture was poured into water (15 mL)
and extracted with with Et2O (20 × 4 mL). The organic phase was
washed with brine (50 mL), dried (MgSO4), filtered, and evaporated
in vacuo. The crude product was purified by flash chromatography
on silica, eluting with ethyl acetate and pentane (1:19) to give the
title compound 3b as a white solid (448 mg, 60%), mp 52-53 °C.
1H and 13C NMR data were in accordance with the literature.11a
(18) A control experiment showed that microwave heating of diphenyl
ditelluride in DMF at 160 °C for 6 h in the presence of 10 mol-% CuI/bipy
and magnesium did not produce diphenyl telluride (diphenyl ditelluride was
recovered in 86% yield).
(19) (a) Pryor, W. A.; Strickland, T.; Church, D. F. J. Am. Chem. Soc.
1988, 110, 2224. (b) Nishiyama, T.; Hashiguchi, Y.; Sakata, T.; Sakaguchi,
T. Polym. Degr. Stab. 2002, 79, 225. (c) De Koning, A. J. Int. J. Food
Prop. 2002, 5, 451.
(20) Wijtmans, M.; Pratt, D. A.; Valgimigli, L.; DiLabio, G. A.; Pedulli,
G. F.; Porter, N. A. Angew. Chem., Int. Ed. 2003, 42, 4370.
5402 J. Org. Chem., Vol. 71, No. 14, 2006

Compounds 1-5, 7, 8, and 10 were similarly prepared. For
reaction times and temperatures, see Table 2. Amounts of 10, 15,
and 20 mol-%, respectively, of CuI/2,2′-bipyridyl were used for
telluride, selenide, and sulfide synthesis.
of HCl in ether to an ethereal solution of the sulfide. Anal. Calcd
for C18H19NS‚HCl‚0.25Et2O: C, 68.01; H, 6.41. Found: C, 68.10;
H, 6.47.
3-Hydroxy-6-methyl-2-pyridyl Phenyl Telluride (10b). The
reaction mixture was heated in the microwave reactor at 140 °C
for 10 h. The residue was then concentrated under vacuo, extracted
with CHCl3, washed with water, and dried over Na2SO4. The crude
product was purified by flash chromatography using ethyl acetate
and pentane (20:80) to give the title compound 10b as white solid,
Phenyl 6-(2,2,4-Trimethyl-1,2-dihydroquinolinyl) Telluride
(8c). The crude product was purified by flash chromatography on
silica, eluting with Et2O and pentane (5:95) to give the title
1
compound 8c (121 mg, 32%) as a red liquid. H NMR δ 7.57-
7.49 (several peaks, 4H), 7.19-7.16 (several peaks, 3H), 6.34 (d,
J ) 8.0, 1H), 5.33 (b s, 1H), 3.82 (s, 1H), 1.98 (s, 3H), 1.30 (s,
6H). 13C NMR δ 18.7, 31.6, 52.2, 97.8, 114.3, 117.2, 122.8, 126.9,
128.1, 128.7, 129.3, 135.3, 136.4, 141.3, 143.9. MS: m/z 380
(M+1+, 18), 173 (100).
1
mp 150-51 °C. H NMR δ 7.68 (d, J ) 8.1, 2H), 7.28-7.17
(several peaks, 4H), 7.05 (d, J ) 8.3, 1H), 6.07 (b s, 1H), 2.51 (s,
3H). 13C NMR δ 23.5, 113.3, 121.2, 125.2, 128.3, 129.8, 130.6,
137.2, 152.3, 153.0. Anal. Calcd for C12H11NOTe: C, 46.07; H,
3.54. Found: C, 45.88; H, 3.47.
Phenyl 6-(2,2,4-Trimethyl-1,2-dihydroquinolinyl) Selenide
(8d). The crude product was purified by flash chromatography on
silica, eluting with CH2Cl2 and pentane (1:9) to give the title
compound 8d as a light yellow liquid. 1H NMR δ 7.33-7.10
(several peaks, 7H), 6.39 (d, J ) 8.0, 1H), 5.32 (s, 1H), 3.85 (b s,
1H), 1.95 (s, 3H), 1.29 (s, 6H). 13C NMR δ 18.6, 31.5, 52.2, 113.9,
114.0, 122.4, 125.8, 128.0, 128.8, 129.1, 129.9, 131.9, 134.8, 136.7,
143.8. The crystalline hydrochloride of the material was obtained
by addition of HCl in ether to an ethereal solution of the selenide.
Anal. Calcd for C18H19NSe‚HCl‚0.25Et2O: C, 59.87; H, 5.63.
Found: C, 59.84; H, 5.67.
Phenyl 6-(2,2,4-Trimethyl-1,2-dihydroquinolinyl) Sulfide (8e).
The crude product was purified by flash chromatography on silica,
eluting with CH2Cl2 and pentane (1:9) to give the title compound
8e as a colorless liquid. 1H NMR δ 7.25-7.12 (several peaks, 7H),
6.45 (d, J ) 8.0, 1H), 5.36 (s, 1H), 3.91 (b s, 1H), 2.00 (s, 3H),
1.35 (s, 6H). 13C NMR δ 18.7, 31.6, 52.3, 113.8, 117.8, 122.3,
125.0, 126.7, 128.1, 128.8, 128.9, 131.0, 135.8, 140.5, 144.0. The
crystalline hydrochloride of the material was obtained by addition
3-Hydroxy-6-methyl-2-pyridyl Phenyl Selenide (10c). The
reaction mixture was extracted with ethyl acetate, and purification
was carried out by flash chromatography using CH2Cl2 and MeOH
(99:1) as eluent. Selenide 10c was obtained as a white solid, mp
1
126-127 °C. H NMR δ 7.41-7.37 (several peaks, 2H), 7.26-
7.20 (several peaks, 4H), 7.10 (d, J ) 8.2, 1H), 6.14 (s, 1H), 2.51
(s, 3H). 13C NMR d 23.6, 122.9, 125.7, 127.6, 129.5, 131.4, 138.4,
151.6, 151.7. MS: m/z 266 (M+1+, 100), 204 (18), 102 (41).
Acknowledgment. The Swedish Research Council is grate-
fully acknowledged for financial support.
Supporting Information Available: General synthetic details,
experimental and spectral data for compounds 5a and 7a,b and
copies of 1H and 13C NMR spectra of compounds 5a, 7a,b, 8c-e,
and 10b-d in pdf format. This material is available free of charge
via the Internet at http://pubs.acs.org.
JO060690A
J. Org. Chem, Vol. 71, No. 14, 2006 5403