4912
D. Prajapati, S. Gadhwal / Tetrahedron 60 (2004) 4909–4913
4.2. Reaction of hydrazinoyl bromide 9 with isatin imines
8 and synthesis of spiroindoles 11
(90 MHz, CDCl3) 7.8–7.9 (bs, 1H, NH), 6.3–7.3 (m, 12H,
ArH), 2.4–2.5 (s, 3H, COCH3), 2.1–2.2 (s, 3H, CH3); dc
(100 MHz, CDCl3), 37.6 (CH3), 41.2 (COCH3), 97.0 (spiro
carbon), 111.1, 112.8, 119.1, 122.6, 124.1, 126.8, 128.0,
128.8, 129.6, 130.8, 132.0, 133.8, 141.1, 146.6, 147.6, 170.0
(CvO), 174.7 (CvO). EO-MS: m/z 430 (Mþ).
To a solution of isatinimine 8a (10 mmol) in anhydrous
chloroform (15 mL) was added hydrazinoyl bromide 9
(10 mmol) and stirred well. To this solution, dry triethyl-
amine (15 mmol) dissolved in 10 mL of anhydrous CHCl3
was added dropwise in 40 min. After stirring for 10 min the
solution was refluxed with stirring for 3 h and cooled to
room temperature (monitored by TLC). The chloroform was
then removed under reduced pressure and the residue was
treated with dry benzene (20 mL). The precipitated
triethylamine hydrobromide was filtered off and the solvent
was removed under reduced pressure. The product thus
obtained was then purified by column chromatography on
silica gel using CHCl3 as eluent and isolated the
corresponding cycloadduct 11a in 80% yield without the
formation of any side products. The physical and spectral
data of the cycloadduct is recorded below.
4.2.5. Compound 11e. Yellow semi solid, yield 65%
(3.10 g). [Found: C, 60.53; H, 3.85; N, 11.90 C24H19BrN4O2
requires C, 60.63; H, 4.00; N, 11.79%]. nmax (cm21) 3342
(N–H), 1745 (CvO), 1663 (COCH3): dH (90 MHz, CDCl3)
8.3 (bs, 1H, NH), 7.75–7.83 (m, 12H, ArH), 2.35–2.5 (s,
3H, COCH3), 2.1–2.15 (s, 3H, CH3); dc (100 MHz, CDCl3),
35.9 (CH3), 42.5 (COCH3), 96.3 (spiro carbon), 111.8,
113.8, 120.1, 122.8, 125.0, 127.8, 128.1, 128.8, 129.6,
130.6, 131.8, 133.6, 140.8, 145.6, 169.9 (CvO), 174.9
(CvO). EI-MS: m/z 474 (Mþ).
Acknowledgements
4.2.1. Compound 11a. Yellow needles, yield 80% (3.15 g),
mp 148–51 8C. [Found: C, 72.62; H, 5.14; N, 14.18.
C24H20N4O2 requires C, 72.72; H, 5.05; N, 14.14%]. nmax
(cm21) 3339 (N–H), 1750 (CvO), 1660 (COCH3): dH
(90 MHz, CDCl3) 8.25 (bs, 1H, NH), 6.4–7.5 (m, 13H,
ArH), 2.5–2.55 (s, 3H, COCH3), 2.18–2.2 (s, 3H, CH3); dc
(100 MHz, CDCl3) 36.2 (CH3), 41.1 (COCH3), 96.8 (spiro
carbon), 111.3, 113.6, 119.5, 122.6, 125.8, 127.7, 128.4,
128.6, 129.7, 130.5, 131.8, 133.0, 141.7, 145.8, 170.03
(CvO), 175.11 (CvO). EI-MS: m/z 396 (Mþ). Similarly
other isatin imines were reacted with hydrazinoyl bromides
and the corresponding cycloadducts 11b–e were isolated in
high yields. The physical and spectral data of the
spiroindoles are recorded below.
The authors thank the Department of Science and
Technology, New Delhi for financial assistance and D. D.
Laskar for carrying out some of the experiments. We also
thank Director, Regional Research Laboratory, Jorhat for
his keen interest and constant encouragement to perform
this work.
References and notes
1. (a) Carter, S. K.; Crooke, S. T. Mitomycin C. current status
and new development. Academic: New York, 1979.
(b) Verboom, W.; Reinhurt, D. N. In Innovative approaches
to drug research; Harns, A. F., Ed.; Elsevier: Amsterdam,
1986; p 437. (c) Jones, G. B.; Moody, C. J. J. Chem. Soc.,
Chem. Commun. 1988, 1009.
4.2.2. Compound 11b. Yellow needles, yield 82% (3.30 g),
mp 188–90 8C. [Found: C, 73.09; H, 5.27; N, 13.63.
C25H22N4O2 requires C, 73.17; H, 5.36; N, 13.65%]. nmax
(cm21) 3363 (N–H), 1739 (CvO), 1660 (COCH3): dH
(90 MHz, CDCl3) 8.10 (bs, 1H, NH), 6.3–7.3 (m, 12H,
ArH), 2.45–2.4 (s, 3H, COCH3), 2.1–2.2 (s, 6H, CH3); dc
(100 MHz, CDCl3), 35.9 (CH3), 36.1 (CH3), 40.9 (COCH3),
97.02 (spiro carbon), 111.9, 113.1, 118.8, 122.6, 124.8,
127.1, 128.2, 128.9, 129.1, 130.8, 132.1, 133.5, 141.8,
146.1, 147.2, 171.11 (CvO), 175.19 (CvO). EI-MS: m/z
410 (Mþ).
2. (a) Maliepaard, M.; de Mol, N. J.; Janssen, L. H. M.;
Hoogvliet, J. C.; van der Neut, W.; Verboom, W.; Reinhoudt,
D. N. J. Med. Chem. 1993, 36, 2091. (b) Kinoshita, K.; Uzu,
K.; Nakano, K.; Takahashi, T. J. Med. Chem. 1971, 14, 109.
and references cited therein.
3. Iyenger, B. S.; Lin, H.-J.; Cheng, L.; Remers, W. A.; Bradner,
W. T. J. Med. Chem. 1981, 24, 975, and references cited
therein.
4.2.3. Compound 11c. Yellow needles, yield 80% (3.45 g),
mp 75–77 8C. [Found: C, 70.29; H, 5.25; N, 13.03
C25H22N4O3 requires C, 70.42; H, 5.16; N, 13.14%]. nmax
(cm21) 3253 (N–H), 1729 (CvO), 1679 (COCH3): dH
(90 MHz, CDCl3) 8.05–8.15 (bs, 1H, NH), 6.4–7.5 (m,
12H, ArH), 4.6–4.7 (s, 3H, OCH3), 2.5–2.6 (s, 3H,
COCH3), 1.15–1.2 (s, 3H, CH3); dc (100 MHz, CDCl3),
37.6 (CH3), 41.2 (COCH3), 60.1 (OCH3), 96.2 (spiro
carbon), 111.5, 113.6, 120.1, 121.8, 124.8, 127.1, 128.1,
128.8, 129.2, 130.5, 131.2, 133.0, 140.8, 146.1, 168.8
(CvO), 172.81 (CvO). EI-MS: m/z 426 (Mþ).
4. (a) Szantay, C. The alkaloids; Cordell, G. A., Ed.; Academic:
London, 1998; Vol. 50. (b) Lounasmaa, M.; Hankinen, P.;
Westersund, M. The alkaloids; Cordell, G. A., Ed.; Academic:
London, 1999; Vol. 52. Chapter 2.
5. Danishefsky, S. J.; Schkeryantz, J. M. Synlett 1995, 475.
6. Ziegler, F. E.; Jeroncic, L. O. J. Org. Chem. 1991, 56, 3479.
7. Lee, S.; Lee, W. M.; Sulikowski, G. A. J. Org. Chem. 1999,
64, 4224.
8. (a) Molander, G. A.; Schmitt, M. H. J. Org. Chem. 2000, 65,
3767. (b) Vedejs, E.; Klapars, A.; Naidu, B. N.; Piotrowsaki,
D. W.; Tucci, F. C. J. Am. Chem. Soc. 2000, 122, 5401.
9. Jager, V.; Buss, V.; Schwab, W. Tetrahedron Lett. 1978, 3133.
10. (a) Kotera, K.; Takano, Y.; Matsuura, A.; Kitahonoki, K.
Tetrahedron 1970, 26, 539. (b) Lang, S. A., Jr.; Lin, Y. I.
Comprehensive heterocyclic chemistry; Katritzky, A. R., Rees,
C. W., Eds.; Pergamon: Oxford, 1984; Vol. 6.
4.2.4. Compound 11d. Yellow needles, yield 70% (3.0 g),
mp 197–99 8C. [Found: C, 66.98; H, 4.33; N, 12.88.
C24H19ClN4O2 requires C, 66.89; H, 4.41; N, 13.00%]. nmax
(cm21) 3337 (N–H), 1742 (CvO), 1660 (COCH3): dH