R. Pratap, V. J. Ram / Tetrahedron Letters 50 (2009) 2805–2807
2807
Acknowledgments
N
N
O
O
The authors are thankful to CSIR, New Delhi, and AICTE, New
Delhi, for financial support and to the Sophisticated Analytical
Instrument Facility, CDRI, Lucknow, for providing spectroscopic
data. The authors are also thankful to Dr. Alberto Di Salvo for edit-
ing the manuscript.
CN
CN
DMF/KOH
+
O
S
R
S
R
9
8
4
N
9
R
Yields (%)
References and notes
a
b
c
d
e
piperidin-1-yl
H
H
H
H
89
89
84
83
1. Nielson, T. K.; Sigur, C. H.; Jorgensen, O.; Hansen, P.; Kirso, U. Environ. Sci.
Technol. 1997, 31, 1102.
2. Bleeker, E. A. J.; Wiegman, S.; De Voogt, P.; Kraak, M.; Leslie, H. A.; de Hass, H.;
Admiraal, W. Rev. Environ. Contam. Toxicol. 2002, 173, 39.
3. Pearlman, R. S.; Yalkowsky, S. H.; Banergee, S. J. Phys. Chem. Ref. Data 1984, 13,
1555.
4-methylpiperidin-1-yl
4-benzylpiperidin-1-yl
4-benzylpiperazin-1-yl
piperidin-1-yl
OCH3 77
4. (a) Kumar, S.; Reubeu, P.; Kumar, A. Polycyclic Aromat. Compd. 2004, 24, 289–
297; (b) Iwoa, A.; Lee, M. L.; Castle, R. N. J. Heterocycl. Chem. 1980, 17, 1259–
1264.
Scheme 3. Synthesis of 2-thia-3,4,7,8-tetrahydrobenzo[c]phenanthrenes 9.
5. Lee, M. L.; Willey, C.; Castle, R. N.; White, C. M. In Polynuclear Aromatic
Hydrocarbons, Battelle Press, Columbus, OH, 1980; pp 59–73.
6. Nishikoka, M.; Lee, M. L.; Castle, R. N. Fuel 1986, 65, 390.
7. Willey, C.; Iwoa, M.; Castle, R. N.; Lee, M. L. Anal. Chem. 1981, 53, 400.
8. Croisy, A.; Mispelter, J.; Lhoste, J. M.; Zajdela, F.; Jacquignon, P. J. Heterocycl.
Chem. 1984, 21, 353.
9. (a) Cheng, J. X.; Zheng, Y.; West, M.; Tang, M. Cancer Res. 1998, 58, 2170–2175;
(b) Denisenko, M. F.; Pao, A.; Tang, M.; Pfeifer, G. P. Science 1996, 274, 430–432.
10. Cheng, C. C. In Structural Aspects of Antineoplastic Agents—A New Approach; Ellis,
G. P., West, G. B., Eds.; Progress in Medicinal Chemistry; Elsevier Science
Publisher, B.V. (Biomedical Division): Amsterdam, 1988; Vol. 25, pp 35–83.
11. Pratap, R.; Ram, V. J. Tetrahedron Lett. 2007, 48, 2755.
N
N
O
O
O
CN
CN
DMF/KOH
+
X
O
R
O
R
10
11
4
12. Pratap, R.; Ram, V. J. Tetrahedron Lett. 2007, 48, 7982.
13. General procedure for the synthesis of 2-oxa/thia-6-sec.amino-3,4,7,8-tetrahydro-
1H-benzo[c]phenanthrene-5-carbonitriles 6/9: A mixture of 4 (0.5 mmol), 4-
Scheme 4. Attempt to synthesize 6-sec.amino-8,13-dihydro-7H-14-oxa-benzo[c]
chrysene-5-carbonitrile 11.
oxotetrahydropyran
5 or 4-oxotetrahydrothiopyran 8 (0.6 mmol), and
powdered KOH (34.2 mg, 0.6 mmol) in DMF (4 mL) was stirred at room
temperature for 1.5–3 h. During this period all the starting material was
consumed with the appearance of a new spot on TLC. Thereafter, the reaction
mixture was poured onto crushed ice under vigorous stirring followed by
neutralization with 10% HCl (5.0 mL). The resulting precipitate was filtered,
washed with water, dried, and purified by elution over neutral alumina using
2% ethyl acetate in hexane as eluents. (6a). Yield 89%; mp 188–190 °C; 1H NMR
(CDCl3, 300 MHz): d 1.59–1.74 (m, 6H, CH2), 2.65–2.69 (m, 2H, CH2), 2.75–2.80
(m, 2H, CH2), 3.09 (t, J = 6.18 Hz, 2H, CH2), 3.23 (br s, 4H, CH2) 4.08 (t,
J = 6.27 Hz, 2H, CH2), 4.89 (s, 2H, CH2), 7.22–7.33 (m, 4H, ArH); 13C NMR (CDCl3,
75 MHz): d 22.9, 23.4, 25.5, 26.5, 28.1, 51.1, 63.9, 67.5, 106.2, 117.2, 124.7,
126.3, 126.6, 127.0, 27.3, 131.7, 134.1, 135.4, 137.4, 138.9, 151.1; IR (KBr):
2209 (CN) cmÀ1; mass (ESI-MS) m/z 345 [M++1]; HRMS (70 eV): M+ Calcd for
C23H24N2O: 344.18886. Found: 344.18902; Anal Calcd for C23H24N2O: 344.18 C,
80.20; H, 7.02; N, 8.13. Found: C, 80.27; H, 7.11; N, 8.09. (9d). Yield 83%; mp
154–156 °C; 1H NMR (CDCl3, 300 MHz): d 2.62 (br s, 4H, CH2), 2.70–2.75 (m,
4H, CH2), 2.96 (t, J = 6.48 Hz, 2H, CH2), 3.24 (t, J = 6.48 Hz, 2H, CH2), 3.30 (br s,
4H, CH2), 3.58 (s, 2H, CH2), 393 (s, 2H, CH2), 7.22–7.41 (m, 9H, ArH); 13C NMR
(CDCl3, 75 MHz): d 24.1, 24.7, 26.1, 27.4, 28.0, 49.7, 52.7, 62.0, 106.7, 116.6,
124.9, 125.8, 126.3, 126.9, 127.5, 127.9, 129.7, 131.8, 134.5, 137.0, 137.7, 138.9,
140.4, 149.2; IR (KBr): 2211 (CN) cmÀ1; mass (ESI-MS) m/z 452 [M++1]; HRMS
(70 eV): M+ Calcd for C29H29N3S 451.20822; found 451.20811; Anal Calcd for
C29H29N3S: 451.20 C, 77.12; H, 6.47; N, 9.30. Found: C, 77.25; H, 6.47; N, 9.33.
(Scheme 4). From this reaction, it was concluded that the presence
of fused aryl systems decreased the reactivity of pyran-4-one prob-
ably due to conjugation of the carbonyl function with the aromatic
ring.
All the compounds synthesized were characterized by spectro-
scopic techniques and data for a representative compound are pre-
sented in the reference section.13
In summary, the synthesis of partially reduced oxo- and thia-
analogs of benzo[c]phenanthrenes (6, 9) is reported for the first
time through base-catalyzed ring transformation of suitably func-
tionalized 2-oxobenzo[h]chromene by 4-oxotetrahydropyran and
4-oxotetrahydrothiopyran, respectively, through C–C insertion, in
excellent yields. The protocol provides an efficient and concise syn-
thesis of polycyclic partially reduced heteroaromatics not easily
obtainable by other routes. The process is very simple and viable
using very economical reagents.