New transformation of 2-substituted 5-nitropyrimidines by the action of the enamine form of N-methylacetone imine [4]

Full text of DOI:10.1023/A:1021229920679

Chemistry of Heterocyclic Compounds, Vol. 38, No. 9, 2002
NEW TRANSFORMATION OF
2-SUBSTITUTED 5-NITROPYRIMIDINES
BY THE ACTION OF THE ENAMINE
FORM OF N-METHYLACETONE IMINE
M. A. Yurovskaya, Ya. A. Ivanenkov, and A. V. Starkova
Keywords: 2-amino-5-nitropyrimidine, 2-hydroxy-5-nitropyrimidine, 5-nitro-2-phenylpyrimidine,
2-amino-2-phenylpyrimidine,
2-hydroxy-2-phenylpyrimidine,
5-methyl-2-phenylpyrimidine,
N-methylacetone imine, nucleophilic transformations, [2+4] cycloaddition.
Of the many reported nucleophilic transformations of 5-nitropyrimidines, there have only been two
examples involving the action of enamines. Shkil and Sagitullin [1] reported the transformation of
5-nitropyrimidine to give the corresponding bicyclic 3-nitropyridine by the action of an enamine of
cyclododecanone. Gromov [2] reported the conversion of 5-nitro-2-phenylpyrimidine to give N-alkyl-p-
nitroanilines in ~30% yield and methylnitropyridine in ~4% yield in aqueous acetone solutions of alkylamines
and dialkylamines (the in situ formation of enamines may be assumed in this case).
We are the first to report a new direction in the transformation of 2-substituted 5-nitropyrimidines 1a-c
by the action of N-methylacetone imine in DMF at ~20°C leading to formation of 2-substituted
5-methylpyrimidines 2a-c as the major reaction products.
NHMe
NMe
O2N
CH2=C–Me
Me–C–Me
N
N
R
1a–c
NHMe
O2N
Me
Me
N
+
+
N
N
R
4
2a–c
NO2
3
(for R = Ph)
2 a (47%), b (48%), c (37%)
1, 2 a R = Ph, b R = NH2, c R = OH
Thus, 5 mmol of freshly prepared N-methylacetone imine [6] was added to a solution of 1 mmol
nitropyrimidine 1a-c in 5 ml DMF. Nitropyrimidines 1a-c were prepared according to known methods [3-5].
The reaction mixture was maintained for 120 h at ~20°C. At the end of the reaction, 2a-c separated as a
__________________________________________________________________________________________
M. V. Lomonosov Moscow State University, 119899 Moscow, Russia; e-mail:
yumar@org.chem.msu.su. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1298-1300,
September, 2002. Original article submitted June 5, 2002.
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0009-3122/02/3809-1140$27.00©2002 Plenum Publishing Corporation

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precipitate. In all cases, the mass spectral data and identity of the IR and H NMR spectral data with the data
reported by various workers [7-9] indicate formation of 2-substituted 5-methylpyrimidines 2a-c.
We propose the following mechanism for the formation of 2a-c:
MeHN
Me
NHMe
Me
C–NO2
– HC
Me
N
N
NO2
H
N
C
N
NO2
NHMe
R
N
R
CH2
N
N
1a–c
5
– MeNH2
Me
– PhCN
– MeNH2
R = Ph
4
R
N
2a–c
The reaction mixtures were analyzed by GC/MS on a HP GC 689 Plus/MSD HP 5973N system. The
analysis indicated formation of 2a, 3, and 4 in 5:1:0.1 ratio in the case of 1a. In the case of 1b, about 50%
unreacted starting reagent was recovered, while 2b and 3 were formed in 5:1 ratio. N-Methyl-p-nitroaniline 3,
which was obtained in all cases, probably through the 4,6-meta-bonding mechanism proposed by Gromov [2],
was identical to the compound described in the literature.
The high content of the tautomeric enamine form of N-methylacetone imine under our conditions [6]
probably permits the unusual participation of the electron-rich dienophile in the Diels–Alder reaction with
inverted electronic requirements with the electron-deficient azadiene system of 5-nitropyrimidines 1a-c. The
consecutive elimination of nitroacetylene (detected by GC/MS) and, then, methylamine from intermediate
bicyclic adduct 5 leads to the formation of 2-substituted 5-methylpyrimidines 2a-c.
We should note that a different pathway for the decomposition of bicyclic intermediate 5 with the
elimination of a stable benzonitrile fragment (also detected by GC/MS) is possible only in the case of
nitropyrimidine 1a (R = Ph). In this case, trace amounts of 3-methyl-5-nitropyridine 4 are specifically formed.
REFERENCES
1.
2.
3.
4.
5.
6.
G. P. Shkil and R. S. Sagitullin, Tetrahedron Lett., 35, 2075 (1994).
S. P. Gromov, Izv. Akad. Nauk, Ser. Khim., 1102 (1994).
Y. Rahamin, J. Sharvit, A. Mandeldaym, and M. J. Sprecher, J. Org. Chem., 32, 3856 (1967).
W. J. Hale, J. Am. Chem. Soc., 32, 87 (1911).
O. R. Roblin, Jr., S. P. Winnek, and J. P. S. Jackson, J. Am. Chem. Soc., 64, 567 (1942).
M. A. Yurovskaya, A. Z. Afanas'ev, E. M. Gizatullina, V. A. Chertkov, and Yu. G. Bundel', Khim.
Geterotsikl. Soedin., 1625 (1987).
7.
8.
9.
M. Robba and R. Moreau, Bull. Soc. Chim. France, 1648 (1960).
R. N. Popova and T. A. Protopopova, Zh. Vses. Khim. Obshch. im. Mendeleeva, 18, 599 (1973).
R. Wightman and R. Holly, Collect. Czech. Chem. Commun., 38, 1381 (1973).
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