A microwave-assisted synthesis of julolidine-9-carboxamide derivatives and their conversion to chalcogenoxanthones via directed metalation

Article abstract of DOI:10.1021/jo070086f

9-Formyljulolidine was oxidized via a microwave-assisted Willgerodt-Kindler reaction to the N-piperidine or N-morpholine julolidine-9-thioamide. 9-Formyl-1,1,7,7-tetramethyljulolidine gave the corresponding N-piperidine tetramethyljulolidine-9-thioamide.

Full text of DOI:10.1021/jo070086f

CHART 1
A Microwave-Assisted Synthesis of
Julolidine-9-carboxamide Derivatives and Their
Conversion to Chalcogenoxanthones via Directed
Metalation
Jason J. Holt, Brandon D. Calitree, Josiah Vincek,
Michael K. Gannon, II, and Michael R. Detty*
Department of Chemistry, The State UniVersity of New York at
Buffalo, Buffalo, New York 14260-3000
mdetty@buffalo.edu
ReceiVed January 15, 2007
form while metal-halogen exchange between n-BuLi and 4
gives only 50% conversion.3
The one method we have found to yield 3 successfully was
a silver oxide catalyzed oxidation,2 which gave 3 reproducibly,
but in only 10-15% isolated yield, not the ∼60% yields reported
by Smith and Yu.4 We sought a general, reproducible means to
oxidize 2 to the carboxylic acid oxidation state. We were also
interested in using amide derivatives of 3 in directed metalation
reactions to prepare chalcogenoxanthones incorporating the
julolidine ring. Directed metalation reactions of derivatives of
3 have not been described.
Several thioamides have been prepared from aldehydes, S,
and morpholine by using a microwave-assisted Willgerodt-
Kindler (W-K) reaction.5 Other amines gave products of amine
oxidation. We report that 9-formyl julolidine (2) is oxidized
with S and piperidine as well as morpholine by using microwave-
assisted W-K reactions. Reaction of 2 with piperidine and S in
N,N-dimethylformamide (DMF) with microwave irradiation
gave thioamide 6 in 91-93% isolated yield (Scheme 1). The
reaction mixture in a sealed microwave vessel was irradiated
at 400 W for 30 min. The temperature of the reaction was held
at 200 °C. Under similar conditions, treating 2 with morpholine
and S gave thioamide 7 in 73-75% isolated yield. These
reactions have been run successfully on a 1-3-g scale. Diethyl-
amine did not give any of the diethylthioamide under these
conditions.
9-Formyljulolidine was oxidized via a microwave-assisted
Willgerodt-Kindler reaction to the N-piperidine or N-
morpholine julolidine-9-thioamide. 9-Formyl-1,1,7,7-tetra-
methyljulolidine gave the corresponding N-piperidine tetra-
methyljulolidine-9-thioamide. The thioamides were converted
to the corresponding carboxamides with trifluoroacetic
anhydride. The amide group directed ortho-metalation in the
julolidine system, but not in the tetramethyljulolidine system.
The resulting anion was captured by dichalcogenide elec-
trophiles. The resulting products were converted to chalco-
genoxanthones with phosphorus oxychloride and triethyl-
amine (POCl3/Et3N).
Julolidine (1, Chart 1) is an intriguing chemical structure.
While 1 is chemically an aniline derivative with two N-alkyl
substituents forming rings back to the aromatic ring, the fused
rings lock the nitrogen lone-pair of electrons into conjugation
with the aromatic ring leading to unusual reactivity. The
aromatic ring is activated to electrophilic attack and Vilsmeier-
Haack formylation of 1 gives 9-formyljulolidine (2) in >90%
yield.1,2 The conformational rigidity gives an electron-rich ring
for electrophilic attack. However, the oxidation of the aldehyde
2 to the carboxylic acid 3 and to other carboxylic acid derivatives
proved to be problematic due to contributions from resonance
form 2a. The conformational rigidity of the julolidyl system
also complicates efforts to convert 9-bromojulolidine (4)2 to
carboxylic acid 3 via the corresponding organolithium or
organomagnesium derivatives 5. The Grignard reagent does not
The W-K reaction also proceeded as a strictly thermal
reaction. The reaction of 2 with piperidine and S in DMF at
153 °C for 30 min also gave 6, but in only 71-78% isolated
yields. The evolution of H2S gas was also apparent from the
strong odor associated with the reaction. In the microwave-
assisted reaction, both the sealed reaction vessel and the
microwave effect itself would lead to increased pressure, which
might limit the evolution of H2S leading to the higher yields in
the microwave-assisted W-K reactions.
The slow addition of trifluoroacetic anhydride6 to thioamides
6 or 7 in CH2Cl2 at room temperature (Scheme 1) gave amides
(3) Heller, H. G.; Oliver, S. N.; Whittall, J.; Brettk, O.; Trundle, C.;
Baskerville, M. W. U.S. Patent 4,818,096, 1989.
(4) (a) Smith, P. A. S.; Yu, T.-Y. J. Org. Chem. 1952, 17, 1281. (b)
Smith, P. A. S.; Yu, T.-Y. J. Am. Chem. Soc. 1952, 74, 1096.
(5) (a) Moghaddam, F. M.; Ghaffarzadeh, M. Synth. Commun. 2001, 31,
317. (b) Poupaert, J. H.; Duarte, S.; Colacino, E.; Depreux, P.; McCurdy,
C. R.; Lambert, D. L. Phosphorus, Sulfur Silicon Relat. Elem. 2004, 179,
1959.
* To whom correspondence should be addressed: Phone: (716) 645-6800,
ext 2200. Fax: (716) 645-6963.
(1) (a) Cai, G.; Bozhkova, N.; Odingo, J.; Berova, N.; Nakanishi, K. J.
Am. Chem. Soc. 1993, 115, 7192. (b) Kauffman, J. M; Imbesi, S. J. Org.
Prep. Proced. Int. 2001, 33, 603.
(2) Pearl, I. A. J. Org. Chem. 1947, 12, 85.
10.1021/jo070086f CCC: $37.00 © 2007 American Chemical Society
Published on Web 03/03/2007
2690
J. Org. Chem. 2007, 72, 2690-2693

SCHEME 1
SCHEME 2
The microwave-assisted W-K reaction5 was also applied to
the oxidation of 9-formyl tetramethyljulolidine 17.9 Reaction
of 17 with piperidine and S in DMF with microwave irradiation
gave thioamide 18 in 69% isolated yield (Scheme 2). The slow
addition of trifluoroacetic anhydride6 to 18 in CH2Cl2 at room
temperature gave amide 19 in 72% isolated yield. All of our
attempts thus far to do directed metalation reactions with 19
and diaryl dichalcogenides have only returned unreacted 19.
In summary, we have described a reliable, two-step procedure
for oxidizing 9-formyl julolidine (2) to julolidine-9-carboxamide
derivatives 8 and 9 and for oxidizing 9-formyl tetramethyl-
julolidine (17) to tetramethyljulolidine-9-carboxamide derivative
19 as well as the first directed metalation reactions of a julolidine
9-carboxamide derivative. Directed metalation of 8 with sec-
BuLi proceeds to give anion 10, which has been captured by
dichalcogenide electrophiles. Chalcogenides 11-13 are cyclized
with POCl3/Et3N to give chalcogenoxanthones 14-16. The
chalcogenoxanthones 14-16 serve as precursors to chalco-
genoxanthylium dyes based on 14-16, which are of potential
interest as photosensitizers for photodynamic therapy10 and as
stimulators/inhibitors of P-glycoprotein.11
8 and 9, respectively, in 90% isolated yield. The same
transformation was also accomplished by using copper nitrate
hexahydrate in CH2Cl2,7 but yields were lower (∼80%).
The two-step conversion of 2 to the carboxamide derivatives
gave overall yields of 84% for 8 and 70% for 9. This method
represents a reliable means for oxidation of 2 to the carboxylic
acid oxidation state and provides amides that can be examined
in directed metalation reactions.
Metalation of
8 with sec-BuLi/tetramethylenediamine
(TMEDA) in THF at -78 °C presumably gives anion 10
(Scheme 1). The addition of bis(3-dimethylaminophenyl) dis-
ulfide, diselenide, or ditelluride8 to 10 gave the diarylchalco-
genides 11 and 12 as oils and diaryltelluride 13 in 30% yield
as a crystalline solid (and recovered 8 in 16% yield). Both 11
and 12 were chromatographically inseparable from small
quantities of unreacted 8 under a variety of conditions. Typically,
the mixtures consisted of 93-97% 11 with 3-7% of 8 and 85-
90% 12 with 10-15% 8. The use of more forcing conditions
or excess sec-BuLi gave reduced yields. The mixtures were used
in the cyclization step without further purification.
The 8/11 mixture or the 8/12 mixture reacted with POCl3/
Et3N8a to give the chalcogenoxanthones 14 and 15, respectively,
as well as unreacted 8, which was readily separated by
chromatography on silica gel at this stage. The yields for 14
and 15 were each 72% for the cyclization of 11 or 12. Telluride
13 reacted with POCl3/Et3N8a to give telluroxanthone 16 in 76%
isolated yield. Importantly, the 2,3,6,7-tetrahydro-1H,5H-benzo-
(i,j)quinolizine ring system (i.e., the julolidyl system) appears
to be stable (a) to sec-BuLi/TMEDA and (b) to the POCl3/Et3N
cyclization conditions.
Experimental Section
Microwave-Assisted W-K Reaction. Microwave reactions were
run in a sealed 80 mL microwave reaction vial. The reaction was
subjected to 25% power at the 400 W setting with an upper
temperature limit of 200 °C for 30 min followed by cooling for 25
min. 9-Formyl julolidine1 (2, 3.00 g, 15.0 mmol) or 9-formyl
tetramethyljulolidine9 (17, 4.00 g, 15.5 mmol), S (1.20 g, 3.8 mmol),
and piperidine (4.44 mL, 45.0 mmol) in 7.5 mL of DMF were
treated in this manner. The resulting red solution was cooled to
ambient temperature and poured into 100 mL of cold water. For 8,
the resulting yellow precipitate was collected by filtration and was
then washed with water (2 × 30 mL) and hexanes (2 × 30 mL).
The precipitate was then dissolved in CH2Cl2, and the resulting
solution was dried over MgSO4 and concentrated. The residue was
purified by chromatography on silica gel, then eluted with 1:9
ether-CH2Cl2 to give 4.17 g (93%) of 6 as a yellow solid. For 18,
the aqueous mixture was extracted with CH2Cl2 (3 × 100 mL) and
the combined organic extracts were washed with brine, dried over
MgSO4, and concentrated. The residue was purified by chroma-
tography on silica gel, then eluted with 1:9 ether-CH2Cl2 to give
3.8 g (69%) of 18 as a yellow-brown oil. Sulfur (0.40 g, 13 mmol),
Directed metalation reactions were unsuccessful with mor-
pholino amide 9. In this system, the morpholine ring appeared
to react with the sec-BuLi/TMEDA and none of the chalco-
genide products related in structure to 11-13 were detected.
(9) Balaganesan, B.; Wen, S.-W.; Chen, C. H. Tetrahedron Lett. 2003,
44, 145.
(6) Masuda, R.; Hojo, M.; Ichi, T.; Sasano, S.; Kobayashi, T.; Kuroda,
C. Tetrahedron Lett. 1991, 32, 1195.
(7) Kristensen, R. B.; Thomsen, I.; Lawesson, S. O. Sulfur Lett. 1985,
3, 7.
(8) (a) Del Valle, D. J.; Donnelly, D. J.; Holt, J. J.; Detty, M. R.
Organometallics 2005, 24, 3807. (b) Brennan, N. K.; Donnelly, D. J.; Detty,
M. R. J. Org. Chem. 2003, 68, 3344.
(10) Wagner, S. J.; Skripchenko, A.; Donnelly, D. J.; Ramaswamy, K.;
Detty, M. R. Biorg. Med. Chem. 2005, 13, 5927.
(11) (a) Gibson, S. L.; Hilf, R.; Donnelly, D. J.; Detty, M. R. Bioorg.
Med. Chem. 2004, 12, 4625. (b) Gibson, S. L.; Holt, J. J.; Ye, M.; Donnelly,
D. J.; Ohulchanskyy, T. Y.; You, Y.; Detty, M. R. Biorg. Med. Chem. 2005,
13, 6394. (c) Tombline, G.; Donnelly, D. J.; Holt, J. J.; You, Y.; Ye, M.;
Gannon, M. K.; Nygren, C. L.; Detty, M. R Biochemistry 2006, 45, 8034.
J. Org. Chem, Vol. 72, No. 7, 2007 2691

2 (1.00 g, 5.0 mmol), and morpholine (1.31 mL, 15.0 mmol) were
treated as described to give 1.08 g (72%) of 7.
For 6: mp 173-175 °C dec; H NMR (500 MHz, CD2Cl2) δ
2932, 2854, 1623, 1606, 1517 cm-1; HMRS (ESI) m/z 341.2585
(calcd for C22H32N2O + H+ 341.2587).
1
Procedure for Lithiation of 8 and Formation of 11-13. Amide
8 (1.10 g, 3.87 mmol, 1 equiv) and TMEDA (0.584 mL, 3.87 mmol,
1 equiv) were dissolved in dry THF (80 mL) in a flame-dried flask
under argon. The resulting solution was cooled to -78 °C and sec-
butyllithium in THF (3.44 mL of a 1.24 M solution, 4.26 mmol,
1.1 equiv) was then added over 3 min. The reaction was stirred
for 10 min and bis(3-dimethylaminophenyl) disulfide (1.19 g,
3.87 mmol), diselenide (1.50 g, 3.87 mmol), or ditelluride (1.92 g,
3.87 mmol) in dry THF (20 mL) was added. The resulting mixture
was stirred at -78 °C for 0.5 h and then warmed to room
temperature with stirring overnight. The reaction was then quenched
with saturated NH4Cl (100 mL) and extracted with ether (3 ×
50 mL). The organic extracts were combined, washed with brine
(2 × 40 mL), dried over MgSO4, and concentrated. The crude
products were purified via chromatography on silica gel eluting
with 5% EtOAc/CH2Cl2 to give 1.11 g of a 97:3 mixture of 11 to
8 (60% yield of 11), 0.82 g of an 85:15 mixture of 12 to 8
(37% yield of 12), and 0.46 g (30%) of 13 as a yellow solid, mp
72-76 °C, as well as 0.18 g (16%) of unreacted 8.
6.74 (s, 2 H), 4.24 (br m, 2 H), 3.66 (br m, 2 H), 3,17 (t, 4 H, J )
6 Hz), 2.71 (t, 4 H, J ) 6 Hz), 1.94 (m, 4 H), 1.72 (br m, 2 H),
1.75-1.50 (br m, 4 H); 13C NMR (75.5 MHz, CD2Cl2) δ 201.3,
143.9, 130.5, 126.0, 120.5, 51.8 (br), 50.2, 28.0, 26.5 (br), 24.7,
22.2; IR (KBr) 2933, 2852, 1603, 1506, 1476, 1438, 1311, 1233,
1208, 1170, 1133, 1025, 1006 cm-1; HRMS (ESI) m/z 300.1650
(calcd for C18H24N2S+ 300.1655).
For 7: mp 129-131 °C; 1H NMR (400 MHz, CDCl3) δ 6.83 (s,
2 H), 4.50-3.90 (br m, 4 H), 3.90-3.60 (br m, 4 H), 3.18 (t, 4 H,
J ) 6 Hz), 2.72 (t, 4 H, J ) 6 Hz), 1.95 (t×t, 4 H, J ) 5.8, 6.4
Hz); 13C NMR (75.5 MHz, CDCl3) δ 202.6, 144.1, 128.8, 126.3,
120.2, 66.8, 52.1(br), 49.9, 27.7, 21.7; IR (KBr) 2931, 1601, 1507,
1457, 1312, 1227, 1208, 1155, 1112, 1025 cm-1; HRMS (ESI) m/z
303.1525 (calcd for C17H22N2OS + H+ 303.1526). Anal. Calcd for
C17H22N2OS: C, 67.51; H, 7.33; N, 9.26. Found: C, 67.26; H, 7.22;
N, 9.17.
For 18: 1H NMR (500 MHz, CDCl3) δ 7.09 (s, 2 H), 4.30 (br
s, 2 H), 3.68 (br s, 2 H), 3.18 (t, 4 H, J ) 6 Hz), 1.74 (t, 4 H, J )
6 Hz), 1.73 (br m, 6 H), 1.26 (s, 12 H); 13C NMR (75.5 MHz,
CDCl3) δ 202.0, 141.5, 129.6, 128.9, 123.4, 52.2 (br), 46.6, 36.4,
32.2, 30.9, 26.3 (br), 24.4; IR (film on NaCl) 2934, 2855, 1600,
1510 cm-1; HRMS (ESI) m/z 357.2358 (calcd for C22H32N2S +
H+ 357.2359).
Thermal W-K Reactions. 9-Formyl julolidine1 (2, 0.500 g, 2.48
mmol) and S (0.200 g, 6.21 mmol) were suspended in 3.2 mL of
dry DMF. Piperdine (0.74 mL, 7.4 mmol) was added to the stirred
mixture and the resulting mixture was heated at 153 °C for 30 min.
The reaction mixture was cooled to ambient temperature and was
poured into 30 mL of CH2Cl2. The resulting solution was washed
with water (2 × 10 mL) and brine (2 × 10 mL), then was
concentrated under reduced pressure. The crude product was
recrystallized from CH2Cl2/MeOH to give 0.595 g (71%) to 0.645
g (78%) of 6 as yellow crystals. On this scale, the microwave-
assisted W-K reaction gave 0.780 g (93%) of 6 following
recrystallization.
For 11: 1H NMR (400 MHz, CDCl3) δ 7.01 (t, 1H, J )
10.0 Hz), 6.72 (s, 1H), 6.58 (s, 1H), 6.45 (d, 1H, J ) 9.0 Hz), 6.36
(d, 1H, J ) 9.5 Hz), 3.76-3.68 (m, 1H), 3.62-3.54 (m, 1H), 3.24-
3.12 (m, 3H), 3.12-3.02 (m, 3H), 2.88 (s, 6H), 2.83 (t, 1H, J )
7.5 Hz), 2.75 (t, 3H, J ) 8.0 Hz), 1.95 (sextet, 2H, J ) 7.5 Hz),
1.85 (quintet, 2H, J ) 8.0 Hz), 1.62-1.46 (m, 4H), 0.92-0.80 (m,
2H); HRMS (ESI) m/z 435.2342 (calcd for C26H33ON3S+ 435.2344).
For 12: 1H NMR (500 MHz, CDCl3) δ 7.00 (t, 1H, J )
8.0 Hz), 6.70-6.69 (m, 2H), 6.50-6.48 (m, 2H), 3.76-3.70 (m,
1H), 3.62-3.54 (m, 1H), 3.26-3.15 (m, 3H), 3.15-3.04 (m, 3H),
2.87 (s, 6H), 2.81 (q, 2H, J ) 6.5 Hz), 2.78-2.70 (m, 2H), 2.00-
1.92 (m, 2H), 1.84 (quintet, 2H, J ) 6.0 Hz), 1.68-1.48 (m, 4H),
1.31 (qt, 2H, J ) 5.5 Hz); HRMS (ESI) m/z 484.1859 (calcd for
C26H33ON380Se + H+ 484.1862)
For 13: 1H NMR (500 MHz, CDCl3, 50 °C) δ 6.95 (t, 1 H, J )
8 Hz), 6.88 (d, 1H, J ) 2.5 Hz), 6.74 (d, 1 H, J ) 8 Hz), 6.69 (s,
1 H), 6.52 (d×d, 1 H, J ) 2.5, 8 Hz), 3.64 (br s, 2H), 3.27 (br s,
2 H), 3.16 (t, 2 H, J ) 6 Hz), 3.06 (t, 2 H, J ) 6 Hz), 2.85 (s, 6
H), 2.83 (br s, 2 H), 2.74 (t, 2 H, J ) 6 Hz), 1.94 (quintet, 2 H, J
) 6 Hz), 1.83 (quintet, 2 H, J ) 6 Hz), 1.60 (br s, 4 H), 1.42
(br s, 2 H); 13C NMR (75.5 MHz, CDCl3) δ 172.0, 151.0, 143.1,
134.0, 129.5, 127.5, 124.2, 123.4, 122.7, 119.0, 117.6, 114.1, 111.1,
50.0, 49.4, 48.5, 42.6, 40.4, 33.8, 27.9, 26.5, 25.4, 24.6, 22.4, 21.7;
IR (KBr) 2926, 2853, 1623, 1584, 1554 cm-1; HRMS (ESI) m/z
534.1748 (calcd for C26H34N3O130Te + H+ 534.1759).
Procedure for Thioamide to Amide Conversion. Trifluoro-
acetic anhydride (0.28 mL, 2.0 mmol, 1.2 equiv) was added slowly
over a period of 5 min to thioamide 6, 7, or 18 (1.7 mmol, 1 equiv)
in dry CH2Cl2 (10 mL). A red color that persisted was observed
upon addition of the trifluoroacetic anhydride. The reaction mixture
was stirred at room temperature for 1 h and was then washed with
an equal volume of aqueous 10% Na2CO3. The organic fraction
was dried over MgSO4 and concentrated to yield a red oil. The
amides 8 and 9 were purified via chromatography on silica gel
eluted with 10% ether in CH2Cl2 to give 0.43 g (90%) of 8 and
0.43 g (90%) of 9 as yellow oils, and 0.56 g (72%) of 19 as a
yellow solid. Products were stored at -20 °C due to discoloration
upon standing at room temperature.
Cyclization of 11-13. To the 8/11 (0.45 g, 1.0 mmol of 11) or
8/12 mixture (0.53 g, 1.0 mmol of 12) in dry acetonitrile (30 mL)
was added Et3N (1.67 mL, 12.0 mmol) followed by POCl3
(1.12 mL, 12.0 mmol). The resulting mixture was stirred for 1 h at
room temperature and was then heated to 80 °C for 2 h. The reaction
was stopped by the addition of 1 N NaOH (100 mL). The organic
products were extracted with CH2Cl2 (3 × 25 mL) and the combined
organic extracts were washed with brine (2 × 25 mL), dried over
MgSO4, and concentrated. The crude product was purified via
chromatography on SiO2 eluted with 5% EtOAc/CH2Cl2 to separate
unreacted 8 from chalcogenoxanthones 14 and 15. Both 14 and 15
were recrystallized from CH3CN to give 0.251 g (72%) of 14 and
0.285 g (72%) of 15. Compound 13 (0.408 g, 0.769 mmol) in dry
acetonitrile (25 mL) was treated with triethylamine (1.29 mL,
9.22 mmol) and phosphorus oxychloride (0.86 mL, 9.2 mmol) as
described to give 0.26 g (76%) of 16 as a yellow solid following
recrystallization from CH3CN.
For 8: 1H NMR (500 MHz, CDCl3) δ 6.87 (s, 2H), 3.56 (br m,
4H), 3.17 (t, 4H, J ) 6.0 Hz), 2.73 (t, 4H, J ) 6.5 Hz), 1.95 (m,
4H), 1.66 (m, 2H), 1.57 (br m, 4H); 13C NMR (75.5 MHz, CD2Cl2)
δ 171.2, 144.2, 126.8, 122.7, 120.6, 50.1, 46.5 (br), 28.0, 26.5,
25.1, 22.2; IR (film on NaCl) 2933, 2852, 1609, 1513 cm-1; HRMS
(ESI) m/z 285.1963 (calcd for C18H24N2O + H+ 285.1961).
For 9: 1H NMR (500 MHz, CDCl3) δ 6.89 (s, 2 H), 3.70-3.63
(br m, 8 H), 3.18 (t, 4 H, J ) 6 Hz), 2.72 (t, 4 H, J ) 6 Hz), 1.95
(q, 4 H, J ) 6 Hz); 13C NMR (75.5 MHz, CDCl3) δ 171.5, 144.3,
126.9, 120.8, 120.4, 67.0, 49.8, 45.9 (br), 27.7, 21.7; IR (film on
NaCl) 3487, 2928, 2846, 1606, 1516 cm-1; HRMS (ESI) m/z
+
286.1675 (calcd for C17H22N2O2 286.1676).
1
1
For 19: mp 151-154 °C; H NMR (500 MHz, CDCl3) δ 7.14
For 14: mp 236-237 °C; H NMR (500 MHz, CDCl3) δ 8.41
(s, 2 H), 3.56 (br s, 4 H), 3.18 (t, 4 H, J ) 6 Hz), 1.74 (t, 4 H, J
) 6 Hz), 1.71-1.64 (br m, 2 H), 1.63-1.56 (br m, 4 H), 1.27 (s,
12 H); 13C NMR (75.5 MHz, CDCl3) δ 171.8, 141.7 129.2, 123.9,
122.0, 46.7, 46.4 (br), 36.5, 32.2, 31.0, 26.1, 24.8; IR (film on NaCl)
(d, 1 H, J ) 9.0 Hz), 8.11 (s, 1 H), 6.78 (d×d, 1 H, J ) 2.5, 9.0
Hz), 6.63 (d, 1 H, J ) 2.5 Hz), 3.27 (t, 2 H, J ) 6.0 Hz), 3.26
(t, 2 H, J ) 5.5 Hz), 3.07 (s, 6H), 2.86 (t, 2 H, J ) 6.0 Hz), 2.77
(t, 2 H, J ) 6.5 Hz), 2.07 (m, 2 H), 1.98 (m, 2 H); 13C NMR
2692 J. Org. Chem., Vol. 72, No. 7, 2007

(75.5 MHz, CDCl3) δ 178.1, 151.6, 145.6, 138.7, 135.0, 130.6,
127.9, 120.2, 118.7, 118.3, 112.7, 111.2, 105.6, 50.3, 49.4, 40.0,
27.7, 24.1, 21.5, 21.2; IR (KBr) 2934, 2833, 2361, 2343, 1591,
1508, 1416, 1355, 1331, 1306, 1175, 1077 cm-1; HRMS (ESI) m/z
351.1518 (calcd forC21H22N2OS + H+ 351.1526).
2.05 (m, 2H), 2.00-1.95 (m, 2H); 13C NMR (75.5 MHz, CDCl3)
δ 184.0, 151.3, 145.9, 133.5, 131.7, 123.3, 122.80, 122.75, 121.8,
120.7, 118.3, 113.6, 112.0, 50.1, 49.6, 39.9, 29.8, 27.5, 21.7, 21.5;
IR (KBr) 2927, 2850, 1584, 1506 cm-1; HRMS (ESI) m/z 449.0868
(calcd forC21H22N2O130Te + H+ 449.0867). Anal. Calcd for
C21H22N2OTe: C, 56.55; H, 4.97; N, 6.28. Found: C, 56.52; H,
5.00; N, 6.14.
1
For 15: mp 243-245 °C; H NMR (500 MHz, CDCl3) δ 8.48
(d, 1 H, J ) 9.2 Hz), 8.18 (s, 1H), 6.77 (d×d, 1 H, J ) 2.6,
9.2 Hz), 6.73 (d, 1 H, J ) 2.6 Hz), 3.28 (m, 4 H), 3.07 (s, 6 H),
2.86 (t, 2 H, J ) 6.4 Hz), 2.71 (t, 2 H, J ) 6.8 Hz), 2.07 (q, 2 H,
J ) 6.8 Hz), 2.00 (q, 2 H, J ) 6.4 Hz); 13C NMR (75.5 MHz,
CDCl3) δ 180.1, 151.5, 145.7, 136.3, 134.1, 132.0, 129.7, 120.2-
(2), 120.2(8), 119.7, 114.6, 111.4, 108.0, 50.2, 49.4, 40.0, 27.6,
25.7, 21.5, 21.4; IR (KBr) 2926, 2843, 2366, 1589, 1572, 1509,
1410, 1303, 1174, 1062 cm-1; HRMS (ESI) m/z 399.0965 (calcd
for C21H22N2O80Se + H+ 399.0970). Anal. Calcd for C21H22N2-
OSe: C, 63.47; H, 5.58; N, 7.05. Found: C, 63.39; H, 5.67; N,
7.02.
Acknowledgment. The authors thank Professor Huw Davies
and the Davies’ research group for access to the preparative
microwave. This research was partially supported by the NSF
REU chemistry program at The University of New York at
Buffalo (CHE-0453206).
1
Supporting Information Available: General methods and H
and 13C NMR spectra of compounds 6-9, 13-16, 18, and 19 and
1H NMR spectra for the 11/8 and 12/8 mixtures. This material is
available free of charge via the Internet at http://pubs.acs.org.
1
For 16: mp 229-231 °C; H NMR (500 MHz, CDCl3) δ 8.54
(d, 1 H, J ) 9.5 Hz), 8.25 (s, 1 H), 6.83 (d, 1 H, J ) 2.5 Hz), 6.74
(d×d, 1 H, J ) 2.5, 9.5 Hz), 3.26 (t, 4 H, J ) 6.75 Hz), 3.05 (s,
6 H), 2.86 (t, 2 H, J ) 6.5 Hz), 2.58 (t, 2 H, J ) 6.5 Hz), 2.11-
JO070086F
J. Org. Chem, Vol. 72, No. 7, 2007 2693