1
596
N. Iranpoor et al.
PAPER
8
0 °C in a vacuum oven. The product weight was 48 g, and con-
to remove the HNO . Then the solution was filtered and the ob-
3
tained 98% of the original polymer, which was characterized by IR
spectroscopy. The resulting solid was ground in a mortar to produce
a yellow powder with irregularly shaped particles. The amount of
CH Cl and CCl that was absorbed by the polymer after 2.5 h stir-
ring at r.t. was found to be 0.7 and 0.6 g per gram of the cross-linked
polymer, respectively.
tained polymer (0.4 g) was reacted with N O (see above) to give
2
4
0.72 g of the PVP–N O .
2
4
2
2
4
Acknowledgment
The authors are thankful to Shiraz University Research Council for
the partial support of this work.
PVP–N O42
9g
2
To a suspension of cross-linked PVP (10 g) in CH Cl (200 mL) at
2
2
0
°C, was added excess of liquid N O (7.0 mL) while stirring the
2 4
References
solution gently. After 1 h, dry N gas was bubbled through the solu-
2
tion in order to extrude the excess of NO gas and then the solvent
(1) (a) Ignarro, L. J. Angew. Chem. Int. Ed. 1999, 38, 1882.
(b) Murad, F. Angew. Chem. Int. Ed. 1999, 38, 1856.
(c) Pfeiffer, S.; Mayer, B.; Hemmens, B. Angew. Chem. Int.
Ed. 1999, 38, 1714.
(2) (a) Montague, P. R.; Gancayco, C. D.; Winn, M. J.;
Marchase, R. B.; Friedlander, M. J. Science 1994, 263, 973.
(b) Kwon, S.; George, S. C. NITRIC OXIDE: Biology and
Chemistry 1999, 3, 348. (c) Feldmam, P. L.; Griffith, O. W.;
Stuehr, D. J. Chem. Eng. News 1993, 71(Dec. 20), 26.
(3) Feelisch, M.; Stamler, J. S. In Methods in Nitric Oxide
Research; Feelisch, M.; Stamler, J. S., Eds.; Wiley:
Chichester, 1996, Chap. 7.
2
was evaporated. The obtained solid was dried under vacuum and
was powdered in a mortar to give PVP supported N O as a pale yel-
2
4
low powder (18.0 g). The capacity of the reagent was determined to
be 5 mmol of N O per gram of the polymer. The reagent could be
2
4
stored in the refrigerator for several months without loss of its
weight or activity.
Nitrosation of Amines; Typical Procedures
CAUTION! N-Nitrosamines and N-nitrosoamides should be re-
garded as potential carcinogenic compounds. The use of an efficient
hood and handling with special care are highly recommended.
(
4) (a) Wang, P. G.; Xian, M.; Tang, X.; Wu, X.; Wen, Z.; Cai,
T.; Janczuk, A. J. Chem. Rev. 2002, 102, 1091. (b) Tanno,
M.; Sueyoshi, S.; Miyata, N.; Umehara, K. Chem. Pharm.
Bull. 1997, 45, 595. (c) Advances in Pharmacology, Vol.
34; Ignarro, L.; Murard, F., Eds.; Academic Press: New
York, 1995, 1–516. (d) Cheng, J.-P.; Xian, M.; Wang, K.;
Zhu, X.; Yin, Z.; Wang, P. G. J. Am. Chem. Soc. 1998, 120,
10266.
N-Nitrosopiperidine
Cross-linked PVP–N O (0.4 g, 2 equiv) was added to a stirred so-
2
4
lution of piperidine (0.172 g, 2 mmol) in CH Cl (4 mL) at r.t. Mon-
2
2
itoring of the reaction mixture by GC showed an immediate
reaction. Then the mixture was filtered. Evaporation of the solvent
under reduced pressure followed by chromatography on a short col-
umn of silica gel using acetone–petroleum ether (1:9) yielded N-ni-
3
3
trosopiperidine (0.22 g, 96%); bp 217–220 °C/760 Torr (Lit. bp
19 °C/760 Torr).
(5) (a) Loeppky, R. N. In N-Nitrosamines and Related N-
Nitroso Compounds, American Chemical Society
Symposium Series, 553; Loeppky, R. N.; Michejda, C. J.,
Eds.; American Chemical Society: Washington DC, 1994.
(b) DeRubertis, F. K.; Craven, P. A. Science 1976, 193, 897.
(6) (a) Guo, Z.; Xian, M.; Zhang, W.; McGill, A.; Wang, P. G.
Bioorg. Med. Chem. 2001, 9, 99. (b) Chemistry and Biology
of N-Nitroso Compounds; Lijinsky, W., Ed.; Cambridge
University Press: Cambridge, 1992.
(7) (a) Seebach, D.; Enders, D. Angew. Chem., Int. Ed. Engl.
1975, 14, 15. (b) Seebach, D.; Enders, D. Angew. Chem.,
Int. Ed. Engl. 1972, 11, 1101. (c) Seebach, D.; Enders, D.
Chem. Ber. 1975, 108, 1293. (d) Seebach, D.; Enders, D.
Angew. Chem., Int. Ed. Engl. 1972, 11, 1102.
2
N-Nitroso-N-methylaniline
A solution of N-methylaniline (0.107 g, 1 mmol) in CCl (2 mL)
4
was placed in a round-bottomed flask (25 mL) equipped with a con-
denser. Cross-linked PVP–N O (0.2 g, 1 mmol) was added and the
2
4
mixture was refluxed for 1.5 h. The mixture was then cooled and fil-
tered. Evaporation of the solvent followed by chromatography on a
short column of silica gel using acetone–petroleum ether (1:9) af-
forded N-nitroso-N-methylaniline (0.125 g, 92%); bp 224–226 °C/
7
60 Torr (dec.) [Lit.33 bp 225 °C/760 Torr (dec.)].
Dealkylation and N-Nitrosation of Triethylamine
To a solution of Et N (0.101 g, 1 mmol) in CCl (5 mL) was added
(8) Jörgensen, K. A.; El-Wassimy, M. T. M.; Lawesson, S.-O.
Tetrahedron 1983, 39, 469.
3
4
cross-linked PVP–N O (0.8 g, 4 equimol) and the mixture was re-
2
4
fluxed for 12 h. The mixture was then cooled and filtered. Evapora-
tion of the solvent followed by chromatography on a short column
of silica gel using acetone–petroleum ether (1:9) yielded N-nitroso-
diethylamine (0.082 g, 80%) as a pale yellow liquid; bp 174–
(9) (a) Kostyukovskii, Ya. L.; Melamed, D. B. Russ. Chem. Rev.
1988, 57, 350. (b) Dictionary of Organic Compounds on
CD-ROM, Version 6:1; Chapman & Hall: London, 1998.
(10) Gdaniec, M.; Milewska, M. J.; Polonski, T. J. Org. Chem.
1995, 60, 7411.
2
3
1
76 °C/760 mm, (Lit. bp 173–176 °C/760 mm).
(
11) Garcia Rio, L.; Leis, J. R.; Iglesias, E. J. Org. Chem. 1997,
62, 4701.
N-Nitroso-N-methylurea
Cross-linked PVP–N O (0.2 g, 1 equiv) was added to a stirred so-
(12) Williams, D. L. H. Nitrosation; Cambridge University Press:
Cambridge, 1988.
2
4
lution of N-methylurea (0.074 g, 1 mmol) in CH Cl (15 mL) at r.t.
2
2
Monitoring of the reaction mixture by GC showed that the reaction
was complete after 200 min. The mixture was filtered. Evaporation
of the solvent under reduced pressure followed by passing through
a short column of silica gel using acetone–petroleum ether (1:9) as
eluent gave N-methyl-N-nitrosourea (0.92 g, 89%); mp 121–123 °C
(13) Zolfigol, M. A.; Zabarjadian, M. H.; Chehardoli, G.;
Keypour, H.; Salehzadeh, S.; Shamsipur, M. J. Org. Chem.
2001, 66, 3619.
(14) Demir, A. S.; Mahasneh, A. S.; Aksoy, H.; Gercek, Z. Synth.
Commun. 1992, 22, 2607.
(
dec.) [Lit.33 mp 123–124 °C (dec.)].
(15) (a) Lovejoy, D. J.; Vosper, A. J. J. Chem. Soc. (A) 1968,
2325. (b) Casado, J.; Castro, A.; Ramon Leis, J.; Quintela,
Regeneration of the Reagent PVP–N O4
M. A. L.; Mosquera, M. Monatsh. Chem. 1983, 114, 639.
2
To regenerate the reagent, the used polymer (0.5 g) was stirred in
CH Cl (10 mL) in the presence of basic alumina (1.0 g) for 15 min
2
2
Synthesis 2003, No. 10, 1591–1597 © Thieme Stuttgart · New York