On the reaction of 3,4-dihydropyrimidones with nitric acid. Preparation and X-ray structure analysis of a stable nitrolic acid [1]

Article abstract of DOI:10.1002/jhet.5570380616

A series of substituted 3,4-dihydro-2-pyrimidones (DHPMs) was reacted with nitric acid under different reaction conditions. Treatment of DHPMs with 50-65% nitric acid at 0°C led to the formation of the corresponding dehydrogenated 2-pyrimidones in moderate to good yields. In contrast, reaction of one representative DHPM with 60% nitric acid at 50°C led to an unusually stable nitrolic acid, involving nitration, nitrosation, dehydrogenation step. The molecular structure of this product was determined by X-ray crystallographic analysis.

Full text of DOI:10.1002/jhet.5570380616

Nov-Dec 2001
On the Reaction of 3,4-Dihydropyrimidones with Nitric Acid.
Preparation and X-Ray Structure Analysis of a Stable Nitrolic Acid [1]
Agnieszka Puchala [a], Ferdinand Belaj [b], Jan Bergman [c], and C. Oliver Kappe* [b]
1345
[a] Institute of Chemistry, Swietokrzyska Academy, Checinska 5, PL-25-020 Kielce, Poland
[b] Institute of Chemistry, Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria
[c] Department of Organic Chemistry, CNT, NOVUM Research Park, S-141 57 Huddinge, Sweden
Received April 24, 2001
A series of substituted 3,4-dihydro-2-pyrimidones (DHPMs) was reacted with nitric acid under different
reaction conditions. Treatment of DHPMs with 50-65% nitric acid at 0 °C led to the formation of the corre-
sponding dehydrogenated 2-pyrimidones in moderate to good yields. In contrast, reaction of one representa-
tive DHPM with 60% nitric acid at 50 °C led to an unusually stable nitrolic acid, involving a formal nitra-
tion, nitrosation, and dehydrogenation step. The molecular structure of this product was determined by X-ray
crystallographic analysis
J. Heterocyclic Chem., 38, 1345 (2001).
In the present paper we discuss the reaction of DHPMs
with nitric acid under different reaction conditions leading
selectively either to dehydrogenated products or to the for-
mation of nitrolic acids.
Introduction.
The search for new energetic compounds with combined
high efficiency and low sensitivity is of considerable cur-
rent interest [2]. In recent years attention focused particu-
larly on pernitrated azaheterocycles [2-6] which in some
cases can be directly obtained by exhaustive nitration of
the corresponding heterocyclic scaffolds [7-10].
Results and Discussion.
Our initial investigations focused on the treatment of
DHPMs 3a with nitric acid of various concentration levels
Some years ago we have reported on the nitration of
dihydropyrimidones of the Biginelli-type (DHPMs), i.e.
compounds 1 [11]. These heterocycles are readily avail-
able by acid-catalyzed three-component condensation of
β-ketoesters, aldehydes, and ureas (Biginelli condensation,
Scheme 1) [12,13]. Using potassium nitrate (2 equivalents)
in concentrated sulfuric acid at 5 °C as nitration medium,
the corresponding 5-nitro-4-(Z)-nitromethylidene pyrimi-
dones 2a,b were obtained from DHPMs 1a,b (R = H, Me).
In the case of the C4-phenyl substituted pyrimidone 1c
(R = phenyl), nitration of the aromatic ring also occurred
(50-65% HNO ) and at different reaction temperatures.
After some experimentation we discovered that a clean
product can be obtained by simple addition of the solid
3
DHPM 3a to 60% HNO at 0 °C. After basic work-up that
3
removed small amounts of an acidic by-product (see struc-
ture 5 below) a colorless substance was obtained in 77%
isolated yield after crystallization, that was readily identi-
fied on the basis of analytical data as the dehydrogenated
1
pyrimidone 4a. In the H nmr spectrum, for example, the
characteristic doublet of the C4 hydrogen at ca. 5.3 ppm in
DHPM 3a disappeared. In addition, the mass spectrum
under these conditions (using 3 equivalents KNO ), pro-
3
showed a peak for the molecular ion at m/z 259 (M+1),
viding mixtures of the para- and meta- substituted prod-
ucts 2c (R = nitrophenyl). The structure and intramolecu-
larly hydrogen-bonded (Z)-configurated geometry was
established by an X-ray analysis of 2a [11].
13
confirming the dehydrogenated structure 4a. In the
C
nmr broad signals were observed for some carbon atoms
due to tautomerism (see structure 4A in Scheme 5). The
transformation 3 → 4 was initially surprising since we had
previously experienced that dihydropyrimidones of the
Biginelli-type are exceedingly difficult to oxidize (i.e.
dehydrogenate) [14]. Such DHPMs have proven to be
quite stable towards a variety of oxidizing agents such as
sodium nitrite in acetic acid, pyridinium chlorochromate
(PCC), cerium ammonium nitrate (CAN), manganese
dioxide, potassium permanganate/clay, tetrachloro-1,4-
benzoquinone (chloranil), and 2,6-dichloro-3,5-
dicyanobenzoquinone (DDQ) [14]. So far no preparatively
useful general procedure for the direct oxidation of
Biginelli compounds has been reported [12]. In fact, only a
single example in the patent literature refers to the use of
nitric acid for this purpose [15].
Scheme 1
We have therefore expanded the scope of this process
and have tried these novel dehydrogenation conditions on
a diverse set of functionalized DHPMs 3a-h. As can be

1346
A. Puchala, F. Belaj, J. Bergman, and C. O. Kappe
Vol. 38
seen from the data presented in Table 1, the method in gen-
eral provides moderate to good yields (29-77%) of pyrimi-
dones 4a-h. However, a fine-tuning of the conditions with
Scheme 3
respect to the HNO concentration and the reaction time
3
was necessary in every case. As a general trend, dihy-
dropyrimidones that bear an alkyl group at the C4 position
(i.e. 3b) are oxidized more rapidly than the C4-aryl substi-
tuted analogs, requiring only 50% HNO and 5 minute
3
reaction time. Other factors such as steric hindrance of the
C4 position (as in 3e) or solubility of the starting materials
may also play a role.
oxides at elevated temperatures [20,21]. All nitrolic acids
and in particular the aromatic analogs appear to have low
intrinsic stability and undergo a number of reactions, even
when stored as solids at low temperatures [17-26]. In con-
trast, nitrolic acid 5 is a pale-yellow solid with an mp of
162-163 °C that can be recrystallized from boiling
methanol/ethyl acetate. No decomposition was observed
even upon prolonged storage as a solid at room tempera-
ture. Characteristically however, the mass spectrum of
nitrolic acid 5 does not show the molecular ion peak
(M+1) at 333, but only the mass of the corresponding nitril
Scheme 2
oxide (loss of "HNO ") at 286 [20,21].
2
Table 1
X-Ray Analysis of 5.
Isolated Yields and Reaction Conditions for the Oxidation of 3a-h to 4a-h
The X-ray structure of 5 (Figure 1) unambiguously con-
firms the nitrolic acid structure and is only the second crys-
tal structure determination of a nitrolic acid reported in the
literature. Furthermore, beside the undissociated acetoni-
trolic acid [17] a zwitterionic dimethyl-ammonium nitro-
late [45] and the salt furo[2,3-c]pyridinium 3-hydroxypyri-
dine-4-nitrolate [46] are found in the Cambridge Structural
Database [44]. In these structures, as well as in 5, the
nitrolic acid moiety adopts the characteristic E configura-
tion which is likely to be a strong contributing factor
towards the stability of this compound; Z configurated
nitrolic acids are known to decompose much more rapidly
[17]. Moreover, the hydroxyimino group and the nitro
group are almost coplanar (e.g. 3.3° in 5); solely in acetoni-
trolic acid the nitro group is markedly twisted (28.6°). By
the planarity of the nitrolic acid group and the ethoxycar-
bonyl group at C5, the nitrolic acid moiety cannot be copla-
nar with the heterocyclic ring due to steric hindrance, but is
twisted out of plane by 81.76(6)° (see Figure 1). Therefore
an intramolecular hydrogen bond between H41 and N3 as
indicated in structure 5A is prevented. It should also be
noted that the unambiguous location of the hydrogen atom
on the oxime oxygen atom in the X-ray structure determi-
nation precludes the gem-nitrosonitromethylidene tautomer
5B to be present in the solid state (Scheme 4) [27].
1
2
3
3,4
R
R
R
HNO
(%)
Time
(min)
Yield
(%)
3
a
b
c
d
e
f
H
H
H
H
H
C H
OEt
OEt
OEt
OMe
OEt
OEt
60
50
65
60
65
60
50
60
30
5
77
54
59
76
29
65
76
61
6
5
Me
4-NO -C H
3-Me-C H
2-CF -C H
10
15
30
10
30
10
2
6
4
6
4
3
6
4
Me C H
Me 3-NO -C H
H
6
5
g
h
OCH Ph
NEt
2
2
6
4
2
C H
6
5
In order to promote conditions that would favor the for-
mation of (per)nitrated products we have subsequently
used higher reaction temperatures in these transformations
involving nitric acid. Addition of solid DHPM 3a to 60%
nitric acid at 50 °C led after 15 minutes and subsequent
aqueous work up to a nitrated product, as evidenced by
1
13
elemental and ms analysis. Inspection of H nmr and
C
nmr data also indicated that a dehydrogenation process
must have occurred. Final confirmation of the structure
was obtained from an X-ray analysis, establishing the
unusual nitrolic acid structure 5 (Figure 1). This com-
pound, obtained in 71% isolated yield after crystallization,
therefore is the result of a formal nitration, nitrosation, and
dehydrogenation process (Scheme 3).
Nitrolic acids (α-nitro oximes) were first reported by
Meyer in 1873 [16]. Since then, only scanty reports deal-
ing with their synthesis, stability and use are found in the
literature [17-26]. There have been some reports dealing
with the rearrangement of nitrolic acids to N-nitroamides
[18,19], and on their thermal fragmentation to nitrile
In the crystal the molecules of 5 form dimers via two
hydrogen bonds lying around centers of symmetry
between H1 and O2' of two pyrimidone rings (see Figure
1). These dimers are connected by hydrogen bonds
between the H atoms of the nitrolic groups and N3" atoms
forming a two-dimensional network of hydrogen bonded

Nov-Dec 2001
On the Reaction of 3,4-Dihydropyrimidones with Nitric Acid
1347
Scheme
4
acid and dihydropyrimidone 3a is somewhat unusual and
deserves further comment, in particular due to the fact that
under different reaction conditions (see Scheme 1) an
entirely different product (involving nitration at C5) is
obtained [11].
A mechanistic rationale for the formation of the various
intermediates and products is presented in Scheme 5. The
first step in the formation of the 5-nitro-4-(Z)-nitromethyli-
dene pyrimidones 2 from DHPMs 1 and KNO /H SO [11]
3
2
4
molecules. Folded sheets lying perpendicular to the crys-
tallographic a-axis (see Figure 2) dominate the packing.
is likely to be a nitration of the active methyl group at the C6
position of the pyrimidine ring by the nitronium cation
Figure 1. Stereoscopic ORTEP [43] plot of 5 showing the atomic numbering scheme and the hydrogen bonds to three other symmetry related molecules
plotted with dashed lines. Symmetry codes: (') 2-x, 1-y, 2-z; (") x, 3/2-y, z-1/2; ("') x, 3/2-y, z+1/2. The probability ellipsoids are drawn at the 50% prob-
ability level.
Mechanistic Considerations.
formed under these nitration conditions (1 → A). In general,
this methyl group in Biginelli DHPMs is readily attacked by
electrophiles [12]. With elemental bromine in chloroform,
for example, selective mono- and dibromination of the
methyl group in 1 can be achieved at 0 °C [29]. It is there-
fore reasonable to assume that under the reaction conditions
used here, involving the electrophilic nitronium species, a
similar pathway is followed. In a subsequent step, the nitro-
nium ion then adds at C5 (i.e. at the electron-rich α position
of the cyclic enamide moiety) to produce the dinitrated
structure 2. It is interesting to note that in contrast to e.g. the
bromination reaction, here a different regioselectivity is
Nitrolic acids (α-nitro oximes) can be synthesized by a
number of methods [17-26]. In many cases the correspond-
ing oximes are nitrated, or nitro derivatives nitrosated [17-
26]. To our knowledge, the one-step formation of nitrolic
acid derivatives by derivatization of a simple methyl group
has been reported only in one case [28]. Here, 2-methyl-
1,4-benzoxazin-2-one was treated with nitrous gases (pre-
pared by reaction of nitric acid with sodium nitrite) in
acetic acid at 35 °C to furnish the corresponding nitrolic
acid in 38% yield [28]. Despite this literature precedent the
high yielding direct formation of nitrolic acid 5 from nitric

1348
A. Puchala, F. Belaj, J. Bergman, and C. O. Kappe
Vol. 38
Figure 2. Stereoscopic ORTEP [43] plot of the packing of 5. The atoms are drawn with arbitrary radii, the intermolecular hydrogen bonds are plotted
with dashed lines.
Table 3
Table
2
Table 4
Selected Bond Angles [°] for 5
Selected Bond Lengths [Å] for 5
Selected Torsional Angles [°] for 5
N(3)-C(4)-C(41)-N(41)
79.1(2)
-94.6(2)
-99.24(16)
87.06(19)
0.7(2)
C(6)-N(1)-C(2)
O(2)-C(2)-N(3)
O(2)-C(2)-N(1)
N(3)-C(2)-N(1)
C(4)-N(3)-C(2)
N(3)-C(4)-C(5)
N(3)-C(4)-C(41)
C(5)-C(4)-C(41)
C(6)-C(5)-C(4)
C(6)-C(5)-C(51)
C(4)-C(5)-C(51)
N(1)-C(6)-C(5)
N(1)-C(6)-C(61)
C(5)-C(6)-C(61)
N(41)-C(41)-N(42)
N(41)-C(41)-C(4)
N(42)-C(41)-C(4)
C(41)-N(41)-O(41)
N(41)-O(41)-H(41)
O(42)-N(42)-O(43)
O(42)-N(42)-C(41)
O(43)-N(42)-C(41)
O(51)-C(51)-O(52)
O(51)-C(51)-C(5)
O(52)-C(51)-C(5)
C(51)-O(52)-C(52)
O(52)-C(52)-C(53)
124.49(14)
121.96(15)
121.16(14)
116.88(14)
119.14(14)
124.60(14)
113.35(14)
121.72(14)
116.50(15)
121.94(14)
121.02(14)
117.66(14)
117.19(14)
125.13(15)
115.63(13)
126.39(14)
117.96(13)
111.13(13)
104.2(15)
125.49(14)
119.00(13)
115.51(12)
125.19(15)
124.42(14)
110.34(13)
115.78(13)
107.45(14)
N(1)-C(6)
N(1)-C(2)
C(2)-O(2)
C(2)-N(3)
N(3)-C(4)
C(4)-C(5)
C(4)-C(41)
C(5)-C(6)
C(5)-C(51)
C(6)-C(61)
C(41)-N(41)
C(41)-N(42)
N(41)-O(41)
N(42)-O(42)
N(42)-O(43)
C(51)-O(51)
C(51)-O(52)
O(52)-C(52)
C(52)-C(53)
1.348(2)
1.387(2)
1.221(2)
1.370(2)
1.317(2)
1.403(2)
1.495(2)
1.390(2)
1.493(2)
1.469(2)
1.266(2)
1.464(2)
1.3638(17)
1.2160(17)
1.2276(18)
1.196(2)
1.3396(19)
1.4599(19)
1.504(2)
C(5)-C(4)-C(41)-N(41)
N(3)-C(4)-C(41)-N(42)
C(5)-C(4)-C(41)-N(42)
C(4)-C(41)-N(41)-O(41)
N(41)-C(41)-N(42)-O(42)
C(4)-C(41)-N(42)-O(43)
C(6)-C(5)-C(51)-O(51)
C(6)-C(5)-C(51)-O(52)
O(51)-C(51)-O(52)-C(52)
C(51)-O(52)-C(52)-C(53)
C(5)-C(6)-C(61)-C(62)
3.8(2)
2.1(2)
-35.7(2)
146.60(14)
-5.9(2)
164.13(13)
-41.2(2)
Table 5
Hydrogen Bonding Geometries [Å, °] for 5
D-H···A
d(D-H)
d(H···A)
d(D···A)
<(DHA)
N(1)-H(1)···O(2)'
O(41)-H(41)···N(3)"
0.93(2)
0.96(3)
1.82(2)
1.67(3)
2.7424(18)
2.6322(18)
173(2)
177(3)
Symmetry transformations used to generate equivalent atoms:
(') 2-x, 1-y, 2-z (") x, 3/2-y, z-1/2
5-chloro-4-chloromethylidene derivative) has also been pro-
posed [30]. In the case of dinitrated product 2 the protonat-
ing and highly acidic reaction conditions using concentrated
sulfuric acid as solvent may also play an important role [11].
observed, not yielding the expected gem-dinitro isomer
B/C. For chlorinations of related DHPMs with PCl /POCl
however, the same regiochemistry (i.e. the formation of a
5
3

Nov-Dec 2001
On the Reaction of 3,4-Dihydropyrimidones with Nitric Acid
1349
For the reaction of DHPM 3 involving concentrated nitric
acid at 50 °C we suggest a different reaction pathway, not
involving initial nitration of the C6 methyl group. In contrast,
we propose that the first step here is a nitrosation of the active
methyl group, in which the resulting nitroso compound D
should rearrange to the oxime tautomer E. Such nitrosation
reactions of activated methyl groups by either nitric acid or
pathway, leading to pyrimidone 4 [34]. Importantly, this
oxidized species is not an intermediate in the formation of
nitrolic acid 5, as confirmed by independent studies sub-
jecting a sample of pyrimidone 4 to the HNO /50 °C reac-
3
tion conditions. The oxidation must therefore occur after
an initial nitration/nitrosation step.
An alternative mechanistic pathway to nitrolic acid 5 is
also presented in Scheme 5. If one would assume that dini-
nitrous gases ("N O ") have been reported in the literature
2
3
[28,31]. The oxime E may subsequently be directly nitrated
by the action of nitric acid ("N O ", Ponzio reaction
tration of DHPM 1 at 50 °C (60% HNO ) leads to gem-
3
2
4
dinitro pyrimidone B/C, an internal redox process would
readily furnish nitrolic acid 5. Although there is literature
precedent for the gem-dinitration of active methylene and
methyl groups [8,35-37], we are not aware of any prece-
dent for a (non-photochemical [38-41]) redox process such
as the hypothetical C → H transformation.
In conclusion, we have demonstrated that depending on
the reaction conditions nitric acid can either dehydrate
DHPMs to the corresponding 2-pyrimidones (3 → 4), or
convert the C6-methyl group into an unusually stable
nitrolic acid function (3 → 5). The further pernitration of
these and the related nitromethylidene systems 2 is cur-
rently under investigation.
[17,24,28,32,33]) to furnish nitrolic acid F, from which the
target compound 5 can be derived by dehydrogenation under
the oxidative conditions present in the reaction medium.
Alternatively, the oxime E may first be dehydrogenated and
subsequently nitrated (E → G → 5). The mechanism pro-
posed here for the transformation of DHPM 3 to nitrolic acid
5 essentially follows the mechanism suggested by Biekert
and Kössel for a related nitrolic acid formation [28]. In most
cases described in the literature the obtained nitrolic acids are
not stable and are readily transformed into furoxanes via
nitrile oxide intermediates [17-28,31-33].
Finally, treatment of DHPMs 3 with 60% HNO at 0 °C
3
follows the standard radical oxidation (dehydrogenation)
Scheme 5

1350
A. Puchala, F. Belaj, J. Bergman, and C. O. Kappe
Vol. 38
3 H, CH ), 3.94 (q, J = 7.5 Hz, 2 H, CH CH ), 7.66 (d, J = 8.0 Hz,
EXPERIMENTAL
3
2
3
2 H, ArH), 8.30 ppm (d, J = 8.0 Hz, 2 H, ArH).
Anal. Calcd for C H N O (303.27): C, 55.44; H, 4.32; N,
14 13
3 5
Melting points were obtained on a Gallenkamp melting point
apparatus, Model MFB-595 in open capillary tubes. The H and
C nmr spectra were obtained on a Bruker AM360 instrument at
360 and 90 MHz, respectively. Chemical shifts in H nmr spectra
13.86. Found: C, 55.15; H, 3.98; N, 13.61.
1
13
Methyl 6-Methyl-3-(3-methylphenyl)-2-oxo-1,2-dihydropyrimi-
dine-5-carboxylate (4d).
1
are reported in ppm from internal tetramethylsilane and are given
in δ units. The solvent for H nmr was hexadeuteriodimethylsul-
This compound was obtained as colorless solid (ethanol), mp
1
175-177 °C; ir: 3150-2600 (NH), 1730 (C=O), 1645 (CO), 1600
foxide unless otherwise stated. Microanalyses were performed on
a Carlo Erba 1106 elemental analyzer. Infrared spectra were
taken on a Perkin-Elmer 298 spectrophotometer in potassium
bromide pellets. Mass spectra were acquired on a Hewlett-
Packard LC/MSD 1100 series instrument in the atmospheric
pressure ionization (API) mode. Nitric acids of various concen-
trations were prepared by dilution of concentrated (65%) nitric
acid. DHPMs 3a-h were prepared according to literature proce-
dures [12].
-1 1
cm ; H nmr: δ 2.33 (s, 3 H, CH ), 2.38 (s, 3 H, CH ), 3.48 (s, 3
3
3
H, OMe), 7.22 ppm (m, 4 H, ArH).
Anal. Calcd for C H N O (258.27): C, 65.11; H, 5.49; N,
14 14
2 3
10.90. Found: C, 64.82; H, 5.46; N, 10.78.
Ethyl 6-Methyl-2-oxo-4-(2-trifluoromethylphenyl)-1,2-dihy-
dropyrimidine-5-carboxylate (4e).
This compound was obtained as colorless solid (ethanol), mp
193-195 °C; ir: 3150-2600 (NH), 1720 (C=O), 1660 (CO), 1590
-1
1
cm ; H nmr: δ 0.78 (t, J = 7.5 Hz, 3 H, CH CH ), 2.45 (s, 3 H,
General Procedure for the Dehydrogenation of DHPMs 3a-h
with Nitric Acid.
2
3
CH ), 3.76 (q, J = 7.5 Hz, 2 H, CH CH ), 7.26-7.76 ppm (m, 4 H,
3
2
3
ArH).
To a stirred and cooled (0 °C) quantity of nitric acid (6.5 mL,
for concentration see Table 1) the appropriate DHPMs 3a-h (4
mmoles) were added portionwise within 5 minutes as solids.
After being stirred for an additional 2 minutes under cooling, the
mixture was allowed to gradually warm to room temperature
within 2-30 minutes (for individual reaction times see Table 1)
the mixture was poured onto crushed ice (ca. 10 g), and then
treated with solid potassium carbonate until a pH of 8 was
reached. The resulting aqueous solution was subsequently
extracted with chloroform (3 x 30 mL), the organic layer dried
over sodium sulfate, and evaporated to dryness. The residual
crude product was purified by recrystallization from the appro-
priate solvent (see below) to give the corresponding pure pyrimi-
dones 4a-h.
Anal. Calcd for C H F N O (326.28): C, 55.22; H, 4.01; N,
8.58. Found: C, 55.15; H, 3.63; N, 8.70.
15 13
3 2 3
Ethyl 1,6-Dimethyl-2-oxo-4-phenyl-1,2-dihydropyrimidine-5-
carboxylate (4f).
This compound was obtained as colorless solid (ethanol), mp
-1
1
219-221 °C; ir: 1720, 1690, 1665 (C=O), 1600 cm ; H nmr: δ
0.84 (t, J = 7.5 Hz, 3 H, CH CH ), 2.50 (s, 3 H, CH ), 3.52 (s, 3
2
3
3
H, NCH ), 3.97 (q, J = 7.5 Hz, 2 H, CH CH ), 7.48 ppm (m, 5 H,
3
2
3
13
ArH); C nmr: δ 13.3, 18.1, 32.9, 61.4, 119.6, 127.4, 128.5,
130.4, 138.4, 155,1, 160.6, 166.6, 169.5 ppm.
Anal. Calcd for C H N O (271.31): C, 66.16; H, 5.92; N,
15 16
2 3
10.29. Found: C, 66.00; H, 6.02; N, 10.29.
Benzyl 1,6-Dimethyl-4-(3-nitrophenyl)-2-oxo-1,2-dihydropy-
rimidine-5-carboxylate (4g).
Ethyl 6-Methyl-2-oxo-4-phenyl-1,2-dihydropyrimidine-5-car-
boxylate (4a).
This compound was obtained as pale yellow solid (ethanol),
-1
1
This compound was obtained as colorless solid (ethanol), mp
191-192 °C; ir: 3150-2600 (NH), 1730 (C=O), 1650 (C=O), 1600
mp 162-165 °C; ir: 1710 (C=O), 1670 (C=O), 1590 cm ; H
nmr: δ 2.54 (s, 3 H, CH ), 3.58 (s, 3 H, NCH ), 5.01 (m, 2 H,
3
3
-1
1
cm ; H nmr: δ 0.82 (t, J = 7.5 Hz, 3 H, CH CH ), 2.38 (s, 3 H,
OCH ), 7.03-8.12 ppm (m, 9 H, ArH).
2
3
2
CH ), 3.95 (q, J = 7.5 Hz, 2 H, CH CH ), 7.48 ppm (m, 5 H, Ph);
Anal. Calcd for C H N O (379.37): C, 63.36; H, 4.52; N,
3
2
3
20 17
3 5
13
C nmr: δ 13.3, 18.4, 61.3, 128.3, 129.1, 131.0, 137.0, 156.41,
166.9 ppm; ms: m/z 259 (M+1), 231, 213.
Anal. Calcd for C H N O (258.27): C, 65.11; H, 5.49; N,
11.07. Found: C, 63.32; H, 4.55; N, 11.32.
N,N-Diethyl 6-Methyl-2-oxo-4-phenyl-1,2-dihydropyrimidine-5-
carboxylic Acid Amide (4h).
14 14
2 3
10.90. Found: C, 64.98; H, 5.49; N, 10.90.
This compound was obtained as colorless solid (ethanol), mp
Ethyl 4,6-Dimethyl-2-oxo-1,2-dihydropyrimidine-5-carboxylate
(4b).
-1
1
149-152 °C; ir: 1660 (C=O), 1610 (C=O), 1580 cm ; H nmr: δ
0.66 and 0.81 (2 t, J = 7.5 Hz, 6 H, CH CH ), 2.24 (s, 3 H, CH ),
2
3
3
This compound was obtained as colorless solid (ethanol), mp
155-157 °C; ir: 3150-2600 (NH), 1720 (C=O), 1665 (C=O), 1610
2.76, 2.91, 3.17, 3.38 (4 m, 4 H, NCH CH ), 7.52 ppm ppm (m, 5
2
3
H, ArH).
Anal. Calcd for C H N O (285.35): C, 67.35; H, 6.71; N,
-1
1
cm ; H nmr: δ 1.26 (t, J = 7.5 Hz, 3 H, CH CH ), 2.31 (s, 6 H,
2
3
16 19
3 2
13
2 CH ), 4.09 ppm (q, J = 7.5 Hz, 2 H, CH CH ); C nmr: δ 13.4,
14.73. Found: C, 66.86; H, 6.66; N, 14.67.
3
2
3
21.0, 60.8, 108.8, 154.7, 164.9 ppm; ms: m/z 197 (M+1).
Anal. Calcd for C H N O (196.21): C, 55.10; H 6.16; N,
14.28. Found: C, 54.97; H, 6.02; N, 14.20.
Ethyl 4-(Hydroxyimino-nitro-methyl)-2-oxo-6-phenyl-1,2-dihy-
dropyrimidine-5-carboxylate (5).
9
12 2 3
To a stirred quantity of 60% nitric acid (8.0 mL) solid DHPM
3a (1.51 g, 5.80 mmoles) was added at 50 °C. After being stirred
at 50 °C for 15 minutes the mixture was poured onto crushed ice
(20 g). The solid precipitate was filtered, washed successively
with water and ether, and dried. Recrystallization from
methanol:ethyl acetate (1:2, v/v) produced 1.36 g (71 %) nitrolic
Ethyl 6-Methyl-4-(4-nitrophenyl)-2-oxo-1,2-dihydropyrimidine-
5-carboxylate (4c).
This compound was obtained as pale yellow solid (ethanol),
mp 217-218 °C; ir: 3150-2600 (NH), 1710 (C=O), 1645 (CO),
-1 1
1590 cm ; H nmr: δ 0.81 (t, J = 7.5 Hz, 3 H, CH CH ), 2.44 (s,
2
3

Nov-Dec 2001
On the Reaction of 3,4-Dihydropyrimidones with Nitric Acid
1351
(1996).
acid 5 as a pale yellow solid, mp 162-163 °C; ir: 3100-2200 (OH,
-1
1
[8] N. Latypov, J. Bergman, A. Langlet, U. Wellmar and U.
Bemm, Tetrahedron, 54, 11525 (1998).
[9] J. Bergman, S. Bergman and T. Brimert, Tetrahedron, 55,
10447 (1999).
[10] A. Langlet, N. V. Latypov, U. Wellmar, P. Goede and J.
Bergman, Tetrahedron Lett. 41, 2011 (2000).
[11] C. O. Kappe and U. G. Wagner, Heterocycles, 29, 761
(1989).
[12] Review: C. O. Kappe, Tetrahedron, 49, 6937 (1993).
[13] Review: C. O. Kappe, Acc. Chem. Res., 33, 879 (2000).
[14] J. J. Vanden Eynde, N. Audiart, V. Canonne, S. Michel, Y.
Van Haverbeke and C. O. Kappe, Heterocycles, 45, 1967 (1997).
[15] T. Isobe, T. Nagao, Y. Takashi, M. Miyagaki, S. Ito, H.
Azuma and M. Ishikawa, Japanese Patent Jpn. Kokai Tokkyo Koho
JP 03 07,265 [91 07,265] (1991); Chem. Abstr., 114, 228948y (1991).
[16] V. Meyer, Ber., 6, 1492 (1873).
[17] For a literature survey on nitrolic acids, see: C. Egan, M.
Clery, A. F. Hegarty and A. J. Welch, J. Chem. Soc., Perkin Trans. 1,
249 (1991).
[18] K. N. Korotaevskii, E. N. Zil`berman, N. K. Petrova, I. Y.
Lubyanitskii, V. K. Fukin and G. N. Matvbeeva, Zh. Org. Khim., 13,
1814 (1977).
[19] K. N. Korotaevskii, E. N. Zil`berman and I. Y.
Lubyanitskii, Zh. Fiz. Khim., 51, 2958 (1977).
[20] C. Matt, A. Gissot, A. Wagner and C. Mioskowski,
Tetrahedron Lett., 41, 1191 (2000) and references cited therein.
[21] C. Grundmann and P. Grünanger, The Nitrile Oxides,
Springer, New York, NY, 1971, pp 51-52.
[22] H. C. Godt and J. F. Quinn, J. Am. Chem. Soc., 78, 1461
(1956).
[23] L. I. Khmel`nitskii, S. S. Novikov and O. V. Lebedov,
Izvest. Akad. Nauk. SSSR., 477 (1961).
[24] N. N. Makahova, I. V. Ovchinikov, V. G. Dubonos, Y. A.
Strelenko and L. I. Khmel`nitskii, J. Chem. Soc., Mendeleev
Commun., 91 (1992).
[25] K. R. Chang and K. Kim, Tetrahedron Lett., 37, 7791
(1996).
[26] A. V. Shastin, T. I. Godovikova and B. L. Korsunskii,
Chem. Heterocyclic Compd. (N.Y.), 35, 72 (1999).
[27] For an X-ray structure determination of a gem-nitrosoni-
tromethylidene compound, see: P. L. Johnson, K. I. G. Reid and I. C.
Paul, J. Chem. Soc. (B), 946 (1971).
NH), 1740 (C=O), 1685 (C=O), 1590, 1550 cm ; H nmr
(methanol-d ): δ 0.88 (t, J = 7.5 Hz, 3 H, CH CH ), 3.95 (q, J =
4
2
3
1
7.5 Hz, 2 H, CH CH ), 7.54 ppm (m, 5 H, ArH); H nmr
2
3
(DMSO-d ): δ 0.76 (t, J = 7.5 Hz, 3 H, CH CH ), 3.91 (q, J = 7.5
6
2
3
13
Hz, 2 H, CH CH ), 7.54 ppm (m, 5 H, ArH); C nmr (DMSO-
2
3
d ): 17.3, 54.4, 102.1, 127.2, 128.3, 129.3, 144.3, 145.3, 167.9,
6
175.5; ms: m/z 286 (M+1, -HNO ), 270, 258, 242, 104.
2
Anal. Calcd for C H N O (332.27): C, 50.61; H, 3.64; N,
14 12
4 6
16.86. Found: C, 50.49; H, 3.55; N, 16.81.
X-Ray Structure Analysis of Nitrolic Acid 5.
All the measurements were performed using graphite-mono-
chromatized Mo K radiation at 90(2)K: molecular formula
α
C H N O , M = 332.28, monoclinic, space group P 2 /c, a =
14 12
4
6
r
1
12.439(4)Å, b = 17.198(4)Å, c = 7.145(2)Å, β = 99.11(2)°, V =
3
-3
-1
1509.2(7)Å , Z = 4, d
= 1.462g cm , µ = 0.117mm . A total
calc
of 3941 reflections were collected (Θ
= 26°), from which
max
2969 were unique (R = 0.0364), with 2498 having I > 2σ(I).
int
The structure was solved by direct methods (SHELXS-97 [41])
2
and refined by full-matrix least-squares techniques against F?
(SHELXL-97 [42]). The non-hydrogen atoms were refined with
anisotropic displacement parameters. The H-atoms attached to
the N or O atoms were refined without any positional constraints
with isotropic displacement parameters. The other H-atoms were
refined with common isotropic displacement parameters for the
H-atoms attached to the same C atom or to the same phenyl ring,
respectively, and with idealized geometries. For 228 parameters
2
final R indices of R = 0.0398 and wR = 0.1013 (GOF = 1.053)
were obtained. The largest peak and hole in a difference Fourier
-3
map were 0.283 and -0.222eÅ , respectively.
Selected bond lengths and angles are listed in Tables 2-5. The
atomic coordinates, displacement parameters, and further details
of the crystal structure investigations are available on requests
from the director of the Cambridge Crystallographic Data Centre,
12 Union Road, GB-Cambridge CB2 1EZ (e-mail:
deposit@ccdc.cam.ac.uk), on quoting the depository number
CCSD-162255, the names of the authors, and the journal citation.
Acknowledgements.
This work was supported by the Austrian Science Fund
(FWF), Project P-11994-CHE. A. P. wishes to thank the Austrian
government for a CEEPUS SK-20 scholarship.
[28] E. Biekert and H. Kössel, Liebigs Ann. Chem., 662, 93
(1963).
[29] G. Zigeuner, H. Hamberger, H. Blaschke and H. Sterk,
Monatsh. Chem., 97, 1408 (1966).
[30] E. L. Khanina, E. E. Liepin`sh, D. K. Mutsenietse and G.
Y. Dubur, Khim. Geterotsikl. Soediin., 668 (1987).
[31] H. R. Snyder and N. E. Boyer, J. Am. Chem. Soc., 77, 4233
(1955).
[32] G. Ponzio, Gazz. Chim. Ital., 56, 497 (1926).
[33] J. H. Boyer and H. Alul, J. Am. Chem. Soc., 81, 4237
(1959).
REFERENCES AND NOTES
*
Author to whom correspondence should be addressed. E-
mail: oliver.kappe@uni-graz.at, Fax. +43-316-3809840.
[1] Synthesis and Reactions of Biginelli Compounds, 27; part
26: O. Lecnik, M. G. Schmid, C. O. Kappe and G. Gübitz,
Electrophoresis, 22, 3198 (2001).
[2] G. Olah and D. Squire, Chemistry of Energetic Material,
Academic Press, 1991.
[34] X.-Q. Zhu, B.-J. Zhao and J. P. Zheng, J. Org. Chem., 65,
8158 (2000).
[3] K. Lee, L. B. Capman and M. D. Coburn, J. Energetic
Materials, 5, 27 (1987).
[35] Y.-C. Liu, H.-Y. Wang, Q.-C. Yang and C. W. Thomas, J.
Chem. Soc., Perkin Trans. 2, 649 (2000).
[4] A. R. Katritzky, D. J. Cundy and J. Chen, J. Energetic
Materials, 11, 345 (1993).
[5] J. E. Marlin and M. O. Killpack, Heterocycles, 34, 1385
(1992).
[36] Z. Gross and S. Hoz, Can. J. Chem., 70, 1022 (1992).
[37] L. W. Deady and N. H. Quazi, Aust. J. Chem. 45, 2083
(1992).
[38] K. Görlitzer, H. J. Baltrusch, E. Goessnitzer and W.
Wendelin, Pharmazie, 55, 35 (2000).
[6] M. Kony and I. J. Dagley, Heterocycles, 38, 595 (1994).
[7] J. Bergman and S. Bergman, Tetrahedron Lett., 37, 9263
[39] G. H. McGall, A. D. Barone, M. Diggelmann, S. P. A.

1352
A. Puchala, F. Belaj, J. Bergman, and C. O. Kappe
Vol. 38
Fodor, E. Gentalen and N. Ngo, J. Am. Chem. Soc., 119, 5081 (1997).
[40] K. Görlitzer and D. Buss, Arch.Pharm., 314, 938 (1981).
[41] K. Görlitzer and C. Heinrici, Arch.Pharm., 321, 477
(1988).
[43] C. K. Johnson, ORTEP. Report ORNL-3794. Oak Ridge
National Laboratory, Tennessee, USA, 1965.
[44] F. H. Allen and O. Kennard, Chem. Des. Autom. News, 8,
31 (1993).
[41] G. M. Sheldrick, SHELXS-97. Program for the Solution
of Crystal Structures. University of Göttingen, Germany, 1997.
[42] G. M. Sheldrick, SHELXL-97. Program for the
Refinement of Crystal Structures. University of Göttingen, Germany,
1997.
[45] T. J. Cholerton, J. Clitherow, J. H. Hunt, J. W. M.
Mackinnon, M. Martin-Smith, B. J. Price, J. Murray-Rust and P.
Murray-Rust, J. Chem. Res., 250, 2818 (1985).
[46] S. Shiotani, H. Morita, M. Inoue, T. Ishida, Y. Iitaka, A.
Itai, J. Heterocyclic Chem., 21, 725 (1984).