Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Nov-Dec 2004
2,4,6-Trifluoropyrimidine. Reactions With Nitrogen Nucleophiles
993
2-Amino-4,6-difluoropyrimidine (3) and 4-Amino-2,6-difluo-
ropyrimidine (4).
mmoles), and sodium carbonate (7.5 mmoles), in ethanol (20
mL) was allowed to stir at room temperature for 22 h. An equal
volume of water was added and the resulting solid was collected
by filtration, washed with water and dried to give a mixture of
components. Column chromatography gave 2,4-difluoro-6-
(a) Using Methanol as Solvent.
To a flask containing 1 mmole of 2,4,6-trifluoropyrimidine (2)
in methanol (10 mL) chilled in an ice bath is bubbled an excess of
anhydrous ammonia. Upon complete addition of the ammonia the
flask and its contents were allowed to warm to room temperature
and stirred overnight. The residue obtained by evaporation of the
solvent under reduced pressure was purified by column chro-
matography. The first fraction (25 %) was determined to be a
phenylaminopyrimidine (9) as the major product (50 %), mp 127-
1
9°; H nmr (dimethylsulfoxide-d ): δ 6.3 (s, 1H, pyrimidine C-5),
6
7.2 (t, 1H, phenyl C-4), 7.4 (t, 2H, phenyl C-3,5), 7.6 (d, 2H,
13
phenyl C-2,6), 10.4 (s, 1H, -NH); C nmr (dimethylsulfoxide-
d ): δ 86 (d), 122, 125, 130, 139, 162.5 (dd), 166 (t), 171.5 (dd).
6
Anal. Calcd. For C H F N : C, 57.97, H, 3.41, N, 20.28.
10
7 2 3
1
mixture of 3 and 4 by H nmr. The second fraction (67 %) was
Found: C, 57.65, H, 3.44, N, 19.89.
identified as 2,4-diamino-6-fluoropyrimidine (5) by comparison
1
Acknowledgements.
with reported mp and H nmr [3].
We are grateful for the financial support from the Research
Excellence Fund of the State of Michigan and the Cancer
Community Services of Mt. Pleasant.
(b) Using Dioxane as Solvent.
The same procedure as described above was employed except
the solvent used was dioxane. Work up in a similar manner
resulted in an 81 % yield of a mixture of 3 and 4 in a ratio of 4:1,
REFERENCES AND NOTES
1
as determined by H nmr. Column chromatography afforded pure
3 and pure 4. These assignments are based on comparison with
1
H nmr literature values [3].
[1a] T. J. Delia, D. Stark, and S. K. Glenn, J. Heterocyclic
Chem., 32, 1177 (1995).
[1b] T. J. Delia and A Nagarajan, J. Heterocyclic Chem., 35, 269
(1998).
[1c] T. J. Delia, B. R. Meltsner, and J. M. Schomaker, J.
Heterocyclic Chem., 36, 1259 (1999).
[1d] J. M. Schomaker and T. J. Delia, J. Heterocyclic Chem., 37,
1457 (2000).
[2] D. J. Brown, The Pyrimidines, John Wiley & Sons
Interscience, New York, NY 1994, p. 371.
[3] I. Wempen and J. J. Fox, J. Med. Chem., 6, 688 (1963).
[4] L. M. Popova and E. P. Studentsov, Russ. J. Org. Chem., 34,
699 (1998).
4,6-Difluoro-(2-hydroxyethylamino)-4,6-difluoropyrimidine (6).
To a solution of 2,4,6-trifluoropyrimidine (2) (2.00 g; 14.9
mmoles) in ethanol (10 mL), cooled to –78°, 2-aminoethanol
(0.92 g; 15.0 mmoles) in ethanol (10 mL) was added dropwise
over 15 min. The mixture was allowed to warm to room tempera-
ture and stirred overnight. After evaporation of the solvent the
residue was chromatographed. The major product 6 was obtained
(1.7 g) in 65 % yield as a cream colored solid which melted at
102-3°; H nmr (dimethylsulfoxide-d ): δ 3.3 (t, 2H, -CH NH-),
3.5 (t, 2H, -O-CH -), 4.7 (t, 1H, HO-), 6.1 (s, 1H, pyrimidine
C-5), 8.0 (t, 1H, -NH-); C nmr (dimethylsulfoxide-d ): δ 43.5,
1
6
2
2
13
6
[5] D. J. Brown and P. Waring, J. Chem. Soc., Perkin Trans. 2,
204 (1974).
59.1, 161.6 (t), 171.7 (dd), 172.3 (dd).
Anal. Calcd. For C H F N O• 0.1 C H O (ethyl acetate): C,
13
[6] This C nmr spectrum at room temperature was run on the
6
7
2
3
4 8 2
41.78; H, 4.28; N, 22.85. Found: C, 42.02; H, 4.26; N, 23.01.
Varian Inova 500 MHz spectrometer.
[7] While the elemental analysis (for C,H, and N) confirmed
the general structure the isomers could not be separated for com-
plete characterization.
2,4-Difluoro-6-phenylaminopyrimidine (9).
Aniline (7.5 mmoles), 2,4,6-trifluoropyrimidine (2) (7.4