Synthesis of novel functionalized derivatives of 5-nitro-3,4- dihydropyrimidin-2(1H)-one by the cyclocondensation of 1-chlorobenzyl isocyanates with N,S- and N,N-nitroketeneacetals

Article abstract of DOI:10.1055/s-2007-965933

The cyclocondensation of 1-chlorobenzyl isocyanates with S,N- and N,N-nitroketeneacetals has been employed to synthesize hitherto-unknown 6-methylthio-5-nitro-3,4-dihydropyrimidin-2(1H)-ones, 8-nitro-2,3,6,7- tetrahydroimidazo[1,2-c]pyrimidin-5(1H)-ones a

Full text of DOI:10.1055/s-2007-965933

PAPER
835
Synthesis of Novel Functionalized Derivatives of 5-Nitro-3,4-dihydropyrimi-
din-2(1H)-one by the Cyclocondensation of 1-Chlorobenzyl Isocyanates with
N,S- and N,N-Nitroketeneacetals
S
ynthesis of 5-Nitr
o
o-3, 4-dihydr
l
opyrim
o
idin-2(1
H
)
-o
d
ne
D
erivativ
y
e
s
myr A. Sukach,a Andriy V. Bol’but,a Alexander Yu. Petin,b Mykhaylo V. Vovk*a
a
Institute of Organic Chemistry National Academy of Science of Ukraine, Murmans’ka 5, 02094 Kiev, Ukraine
Research and Development Center for Chemistry and Biology, National Taras Shevchenko University, Volodymyrs’ka 62, 01033 Kiev,
b
Ukraine
Fax +380(44)5732643; E-mail: mvovk@i.com.ua
Received 7 September 2006; revised 14 December 2006
proaches to DHPM synthesis, for example those proposed
by Atwald and Shutalev,6 have also been reported. The
condensed DHPM nucleus of the alkaloids batzelladines
B and D was constructed using the condensation between
Abstract: The cyclocondensation of 1-chlorobenzyl isocyanates
with S,N- and N,N-nitroketeneacetals has been employed to synthe-
size hitherto-unknown 6-methylthio-5-nitro-3,4-dihydropyrimidin-
2(1H)-ones,
8-nitro-2,3,6,7-tetrahydroimidazo[1,2-c]pyrimidin-
5(1H)-ones and 9-nitro-1,2,3,4,7,8-hexahydro-6H-pyrimido[1,6- acetoacetic ester and a complex derivative of N-a-hy-
droxyalkyl urea;7 in a more recent example, vinyl carbo-
a]pyrimidin-6(1H)-ones. Substitution of the methylthio group in 6-
methylthio-5-nitro-3,4-dihydropyrimidin-2(1H)-ones provided 6-
amino-5-nitro-3,4-dihydropyrimidin-2(1H)-ones, which exist in
obtain partially hydrogenated derivatives of pyrrolo[1,2-
tautomeric equilibrium with 4-imino-5-nitro-3,4,5,6-tetrahydropy-
rimidin-2(1H)-ones. The compounds obtained, if boiled in dioxane
in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU),
eliminate the nitro groups to give substituted 4-imino-3,4-dihydro-
pyrimidin-2(1H)-ones.
diimides were cycloadded to chiral cyclic imines.8 To
c]pyrimidine, constituting the heterocyclic system of sax-
itoxin, Kishi suggested the condensation of 2-carbeth-
oxymethylidenepyrrolidine with isocyanic acid and
acetaldehyde.9
Key words: heterocyclization, tautomerism, 1-chlorobenzyl isocy-
anates, S,N- and N,N-nitroketeneacetals, 3,4-dihydropyrimidones
In contrast to the developments summarized above, the
existing literature offers only scant evidence of 6-alkoxy-,
6-alkylthio-, and 6-amino-substituted DHPMs. Their con-
densed analogues, partially hydrogenated oxazolo(thiazo-
lo)pyrimidines, result from the cycloaddition of
alkenyloxazolines(thiazolines) to aryl and arylsulfonyl
isocyanates.10 The first representatives of 6-amino-3,4-di-
hydropyrimidin-2(1H)-ones were synthesized principally
following the Biginelli reaction, with the difference being
that malonodinitrile or cyanoacetic acid was used instead
of acetoacetic ester.11 It is only very recently that the de-
rivatives of 6-ethoxy- and 6-thiocarbamido-3,4-dihydro-
pyrimidin-2(1H)-one have been obtained.12
The chemistry of 3,4-dihydropyrimidine (DHPM) deriva-
tives, heterocyclic systems of the general formula 1
(Figure 1), has been under vigorous development over the
past two decades.1 Compounds of this class are remark-
able for their diverse biological activity and the scaffold
represented by structure 1 is hence of paramount impor-
tance in medicinal and combinatorial chemistry.2 The
DHPM nucleus is also contained in a number of biologi-
cally significant natural products as, for instance, in bat-
zelladine alkaloids and saxitoxin.3
Our previous studies on the reaction of 1-chloroalkyl iso-
cyanates with C,N-, C,O- and C,S binucleophilic reagents,
led us to a new strategy of constructing functionalized 3,4-
dihydropyrimidones 2. This approach was based on the
[3+3] cyclocondensation of bielectrophilic 1-chloroalkyl
isocyanates 3,13 containing the synthon [–C=N–C=O]2+,
and binucleophilic, deactivated enamines 4, representing
the synthon [–C=C–N–]2– (see Scheme 1).
R
EWG
R
R
Y
EWG = electron-withdrawing group
R = H, Alk, Ar or functional group
Y = O, S, NR
N
N
R
1
Figure 1
In this way, starting from 1-chlorobenzyl isocyanates and
ethyl b-aminocrotonates or b-aminoenones, a number of
hitherto-unknown 1-aryl-substituted 3,4-dihydropyrimi-
dones and 2,3-dihydropyrimido[6,1-c][1,4]benzothiazin-
1(1H)-ones have been obtained.14 Further research along
these lines was aimed at the synthesis of new dihydropy-
rimidine derivatives containing functional groups of vari-
ous electronic nature at positions 5 and 6. It appeared,
therefore, expedient to run cyclocondensations of this
kind with another class of deactivated enamines, S,N-ni-
troketeneacetals 5. Such compounds were chosen because
Classical synthetic access to DHPMs 1 is based on the
Biginelli reaction,4 which has recently been notably de-
veloped through the use of new, efficient Lewis acid cat-
alysts and by applying microwave exposure as well as
solid-phase and fluorine-phase strategies.5 Modified ap-
SYNTHESIS 2007, No. 6, pp 0835–0844
x
x
.
x
x
.2
0
0
7
Advanced online publication: 13.02.2007
DOI: 10.1055/s-2007-965933; Art ID: P10906SS
© Georg Thieme Verlag Stuttgart · New York

836
V. A. Sukach et al.
PAPER
R1
N
R2
2
Table 1 1-Alkyl-4-aryl-6-methylthio-5-nitro-3,4-dihydropyrimi-
din-2(1H)-ones 6
EWG
EDG
EWG
EDG
NCO
Cl
NH
R1
R1
R2
Yield (%)a
NH
R2
6
a
b
c
d
e
f
O
Ph
Me
36
62
60
79
55
77
73
56
44
3
4
2-FC6H4
3-BrC6H4
3-NO2C6H4
4-BrC6H4
4-NO2C6H4
3,4-Cl2C6H3
3-BrC6H4
3,4-Cl2C6H3
Me
R1 = Ar
R2 = H, Alk, Ar
EDG = electron-donating
group
Me
Me
Scheme 1 Retrosynthetic route to functionalized 3,4-dihydropyri-
midin-2(1H)-ones 2
Me
Me
they are easily accessible and constitute highly reactive
1,3-C,N-binucleophiles.15 Previously reported cycliza-
tions of compounds 5 with such bielectrophiles as glyox-
al, ethyl glyoxylate, oxalyl chloride and chlorothioformyl
chloride, furnished pyrrole and thiazole derivatives.16 The
systematic research on the reactions of these highly versa-
tile enamines with propargyl bromide,17 3-bromopropio-
nyl chloride18 and itaconic anhydride19 enabled Junjappa
and co-workers to develop synthetic routes to functional-
ized pyrroles and g-lactones.
g
h
i
Me
Bn
CH2CH2Ph
a Pure, isolated yield.
possibilities for the initial step of the reaction between 3
and 5 (see Scheme 3). The reaction is most likely to start
with the Mannich addition of the nucleophilic b-carbon
atom in the enamine moiety of S,N-nitroketeneacetal 5 to
the activated C=N double bond of the N-chloro-
formylimine form 3¢ of 1-chlorobenzyl isocyanate 3 (path
a). It is highly probable that the formation of new C–C and
N–H bonds in this step proceeds by the diazaene mecha-
nism,21 as in the Michael addition and, as a result, inter-
mediate 8 forms which rapidly cyclizes to the product 6.
An alternative reaction mechanism, discussed in our pre-
vious work,14a is assumed to proceed in two stages, name-
ly isocyanatoalkylation of enamine 5 with the isocyanate
form of compound 3, followed by the intramolecular car-
bamoylation of the alkylamino group. However, the na-
ture of the amino group in reagents 5 was found to affect
the course of the reaction and, hence, one cannot rule out
the possibility that the carbamoylation of the amino group
is just the initial reaction step, which leads to intermedi-
We have found that heating 1-chlorobenzyl isocyanate
(3a) and N-methylnitroketeneacetal (5a) in methylene
chloride for four hours, provided 1-methyl-6-methylthio-
5-nitro-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (6a) in
36% yield. Conducting the reaction in the presence of
triethylamine (Et3N) or N,N-diisopropylethylamine
(DIPEA), used as hydrogen chloride acceptors, resulted in
a reduced yield of compound 6a.
R1
O2N
MeS
O2N
MeS
NCO
Cl
CH2Cl2, ∆
– HCl
NH
R1
+
NHR2
5a–c
N
R2
O
3a–g
6
O
3: R1 = Ph (a), 2-FC6H4 (b), 3-BrC6H4 (c),
4-BrC6H4 (d), 3-NO2C6H4 (e),
4-NO2C6H4 (f), 3,4-Cl2C6H3 (g)
5: R2 = Me (a), Bn (b), CH2CH2Ph (c)
O2N
MeS
NH
R1
N
Cl
3
R1
R2
H
R1
N
O
7
O2N
MeS
O2N
MeS
NH
Cl
3'
a
Scheme 2
O
H
N
N
R2
R2
To obtain compounds 6 with various substituents R1 and
R2, we started from N-alkylnitroketeneacetals 5a–c and 1-
chlorobenzyl isocyanates 3a–g (see Scheme 2 and
Table 1). It can be seen that the yields of pyrimidones 6 in-
creased up to 79% when acceptor substituents are present
on the aromatic ring of the starting isocyanates 3. With N-
aryl-substituted S,N-nitroketeneacetals, a mixture of un-
identifiable products was formed. The isomeric com-
pound 7 was not detected in the reaction mixture.
5
8
b
– HCl
R1
– HCl
R1
O2N
O2N
MeS
NH
O
N
MeS
N
N
R2
O
R2
Since compounds 3 exist as equilibrium mixtures of the
isocyanate and N-chloroformylimine tautomeric forms,20
each having two electrophilic centers, there are several
9
6
Scheme 3
Synthesis 2007, No. 6, 835–844 © Thieme Stuttgart · New York

PAPER
Synthesis of 5-Nitro-3,4-dihydropyrimidin-2(1H)-one Derivatives
837
ates 9 and subsequently to the pyrimidine ring closure aminodihydropyrimidones 11d,f,i,k,l,p in high yields
(path b). (Table 2, entries 5, 9, 12, 14, 15 and 19).
Though 5-nitro derivatives of classical DHPMs have so Aromatic amines enter into this reaction only on boiling in
far been rather poorly studied, they are known to be effi- dioxane to give 6-arylaminodihydropyrimidones in 51–
cient calcium channel modulators, antihypertensive 91% yields (Table 2, entries 4–6, 8, 10, 11, 13, 16–18 and
agents and calcitonin mimetics.22 It should be noted that 20). For instance, aniline, p-toluidine and p-anisidine re-
compounds 6 constitute the first representatives of 3,4-di- act on boiling for four hours, whereas less basic 4-chloro-
hydropyrimidin-2(1H)-ones containing the 6-methylthio aniline requires boiling for 16 hours and 4-cyanoaniline is
group, which imparts pronounced nucleofugic properties actually inert under such conditions.
to nucleophilic substitution reactions. It was found that
To synthesize the condensed analogues of 6-amino-3,4-
compounds 6 readily reacted with aliphatic primary and
dihydropyrimidones, we started from cyclic N,N-nitro-
secondary amines as well as ammonia, at room tempera-
keteneacetals 12a and 12b.
ture in dioxane, so that the amino group replaced the
methylthio group, affording 6-dialkylaminodihydropyr-
imidones 10a and 10b as well as 6-amino- and 6-alkyl-
Compounds 12 reacted with isocyanates 3 at room tem-
perature, in methylene chloride, in the presence of a weak-
ly nucleophilic organic base (DIPEA), to furnish the
Table 2 Synthesis of 1-Alkyl-6-amino-4-aryl-5-nitro-3,4-dihydropyrimidin-2-ones 10 and 11
R1
R1
R1
O2N
O2N
O2N
(R3)2NH
dioxane
R3NH2
NH
NH
NH
6
dioxane, ∆
(R3)2N
N
O
N
N
O
HN
N
O
R2
R3
R2
R3
R2
10
11'
11''
Entry
Compd
R1
Ph
R2
R3
Ratio 11¢:11¢¢,
Yield (%)a
DMSO-d6 (CDCl3)
1
2
10a
10b
11a
11b
11c
11d
11e
11f
Me
Me
Me
Me
Me
Me
Me
Bn
(R3)2N = 1-pyrrolidinyl
–
55
51
87
82
90
64
78
57
45
85
61
91
58
67
87
75
90
54
83
4-BrC6H4
Ph
(R3)2N = 4-morpholinyl
–
4
Ph
0:100 (0:100)
0:100 (0:100)
16:84 (13:87)
100:0
5
Ph
4-ClC6H4
6
Ph
4-MeOC6H4
7
2-FC6H4
3-BrC6H4
3-BrC6H4
3-BrC6H4
4-BrC6H4
3-NO2C6H4
3-NO2C6H4
3-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
H
8
Ph
15:85 (13:82)
45:55 (80:20)
0:100 (0:100)
31:69 (28:72)
83:17 (100:0)
54:46
9
Bn
10
11
12
13
14
15
16
17
18
19
20
11g
11h
11i
Bn
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
4-MeOC6H4
Bn
11j
4-MeOC6H4
Me
11k
11l
98:2 (100:0)
100:0
H
11m
11n
11o
11p
11q
Ph
24:76
4-ClC6H4
4-MeOC6H4
Bn
11:89
32:68
3,4-Cl2C6H3
3,4-Cl2C6H3
91:9 (100:0)
27:73
4-MeC6H4
a Pure, isolated yield.
Synthesis 2007, No. 6, 835–844 © Thieme Stuttgart · New York

838
V. A. Sukach et al.
PAPER
derivatives of 8-nitro-2,3,6,7-tetrahydroimidazo[1,2- An analogous process, in which a nitro group functions as
c]pyrimidin-5(1H)-one 13a and 13d and 9-nitro- a leaving group, has previously been observed for aliphat-
1,2,3,4,7,8-hexahydro-6H-pyrimido[1,6-a]pyrimidin-
ic nitro compounds23 as well as in the Barton–Zard pyrrole
6(1H)-one 13b and 13c in high yields (see Table 3). Start- synthesis.24 Presumably, nitro group elimination proceeds
ing from N,N¢-dibenzylnitroketeneacetal (12c) and the through 1,2-anti elimination of nitrous acid from the ami-
corresponding isocyanate 3c, compound 11f was also dine tautomeric form 11¢¢, as this process is much facili-
thus-obtained in 43% yield.
tated by the location of the proton H6 and the nitro group
in the stable anti-periplanar conformation. It is then evi-
dent that the elimination of this kind should be impossible
for compounds 10, which is indeed the case. Released ni-
trous acid rapidly decomposes and therefore a catalytic
amount of DBU is needed for the reaction to go to com-
pletion. It has been ascertained that the basicity of the
amine involved is of significance, since the conversion
described above does not occur in the presence of triethyl-
amine. 4-Iminopyrimidin-2-ones 14 thus synthesized rep-
resent hitherto-unknown cytosine derivatives.25
Table 3 Synthesis of 8-Nitro-2,3,6,7-tetrahydroimidazo[1,2-c]pyri-
midin-5(1H)-ones 13a and 13d, and 9-Nitro-1,2,3,4,7,8-hexahydro-
6H-pyrimido[1,6-a]pyrimidin-6(1H)-ones 13b and 13c
R1
O2N
HN
O2N
HN
NCO
Cl
DIPEA
CH2Cl2
NH
R1
+
NH
N
O
n
n
3a–g
12a,b
13a–d
All solvents were purified and dried by standard methods. 1H NMR
spectra were recorded in DMSO-d6 or CDCl3 on a Varian Mercury
spectrometer (400 MHz) using TMS as internal standard. 13C NMR
spectra were recorded in DMSO-d6 on a Varian Mercury spectrom-
eter (125 MHz, TMS internal standard). APCI MS data were ob-
tained on an Agilent 1100\DAD\MSD VL G1965a.
Compd 13
R1; n
Yield (%)a
a
b
c
Ph; 0
70
85
83
74
3-NO2C6H4; 1
4-NO2C6H4; 1
3,4-Cl2C6H3; 0
2-Methylamino-2-methylthionitroethene (5a) is commercially
available and was used as received. 1-Chloroalkyl isocyanates 3a–
g,14,26 2-benzylamino-2-methylthionitroethene (5b),27 2-phenethyl-
amino-2-methylthionitroethene (5c),28 2,2-dibenzylaminonitro-
ethene (12c),29 2-(nitromethylen)imidazolidine (12a)30 and 2-
(nitromethylen)hexahydropyrimidine (12b)31 were prepared ac-
cording to literature procedures.
d
a Pure, isolated yield.
On heating a dioxane solution of 4-aryl-6-monoalkyl(ar-
yl)amino-5-nitro-3,4-dihydropyrimidin-2(1H)-ones 11, in
the presence of catalytic amounts of a strong organic base
(DBU), the nitro group is eliminated and the derivatives
of 6-aryl-4-monoalkyl(aryl)imino-3,4-dihydropyrimidin-
2(1H)-ones 14a–f result in high yields (see Table 4).
1-Alkyl-4-aryl-6-methylthio-5-nitro-3,4-dihydropyrimidin-
2(1H)-ones 6; General Procedure
To a stirred solution of S,N-nitroketeneacetal (5a–c; 0.01 mol) in
CH2Cl2 (30 mL) at r.t., a solution of the corresponding 1-chloroben-
zyl isocyanate (3a–g; 0.01 mol) in CH2Cl2 (20 mL) was added. The
reaction mixture was heated for 4 h then the solvent was evaporated
in vacuo and the residue was crystallized from EtOH.
Table 4 Synthesis of 3-Alkyl-6-aryl-4-alkyl(aryl)imino-3,4-di-
hydropyrimidin-2(1H)-ones 14
R1
R1
1-Alkyl-6-amino-4-aryl-5-nitro-3,4-dihydropyrimidin-2(1H)-
ones 10 and 11; General Procedure
H6
B:
O2N
N
NH
NH
To a solution of dihydropyrimidone (6a–h; 0.01 mol) in anhyd di-
oxane (30 mL), the corresponding amine was added. The reaction
mixture was stirred at r.t. for 24 h (in the case of aliphatic amines
and ammonia) or heated for 6 h (in the case of p-chloraniline, 16 h).
The solvent was evaporated in vacuo and the residue was crystal-
lized from EtOH.
DBU
11
– HONO
N
R3
N
R2
O
dioxane, ∆
N
R2
O
R3
11''
14a–f
Compd 14 R1
R2
R3
Yield (%)a
4-(3-Bromophenyl)-1,6-dibenzyl-5-nitro-3,4-dihydropyrimi-
din-2(1H)-ones (11f), 8-Nitro-2,3,6,7-tetrahydroimidazo[1,2-
c]pyrimidin-5(1H)-ones (13a,d) and 9-Nitro-1,2,3,4,7,8-hexahy-
dro-6H-pyrimido[1,6-a]pyrimidin-6-ones (13b,c); General Pro-
cedure
To a stirred solution of N,N-nitroketeneacetal (12a–c; 0.01 mol) and
DIPEA (0.01 mol) in CH2Cl2 (30 mL) at r.t., a solution of the corre-
sponding 1-chlorobenzyl isocyanate (3a,e–g; 0.01 mol) in CH2Cl2
(20 mL) was added. The reaction mixture was stirred for 12 h at r.t.
and the precipitate formed was filtered, washed with H2O (10 × 3
mL) and crystallized from EtOH.
a
b
c
d
e
f
Ph
Me
Bn
Ph
Ph
84
70
88
85
65
90
3-BrC6H4
3-NO2C6H4
4-NO2C6H4
3,4-Cl2C6H3
3,4-Cl2C6H3
Me
Me
Me
Me
4-MeOC6H4
4-MeOC6H4
Bn
4-MeC6H4
a Pure, isolated yield.
Synthesis 2007, No. 6, 835–844 © Thieme Stuttgart · New York

PAPER
Synthesis of 5-Nitro-3,4-dihydropyrimidin-2(1H)-one Derivatives
839
3-Alkyl-6-aryl-4-benzyl(aryl)imino-3,4-dihydropyrimidin-
2(1H)-ones (14a–f); General Procedure
To a solution of the corresponding 6-aminodihydropyrimidone
(0.01 mol) in anhyd dioxane (30 mL), DBU (0.3 g, 0.002 mol) was
added. The reaction mixture was heated for 6 h then the solvent was
evaporated in vacuo and the residue was crystallized from EtOH.
18). A more bulky benzyl substituent at position 1 causes the equi-
librium to shift towards amidine form 11¢¢ (cf entries 8 and 10). A
distinctive feature of the tautomerism found for aminopyrimidones
11 is that the equilibrium between the tautomeric forms is estab-
lished rather slowly. This is evidenced by the APCI MS spectra of
compounds 11, which exhibits two peaks on the chromatogram with
much the same intensity ratio as the content ratio of the tautomeric
1
Structure Assignments and Analytical Data
forms derived from the H NMR spectra in DMSO-d6. Moreover,
The structure of synthesized 3,4-dihydropyrimidones 6a–i was con-
firmed by 1H and 13C NMR spectroscopic as well as APCI MS data.
In DMSO-d6, characteristic 1H resonance doublets were observed at
5.6–5.8 and 8.5–8.9 ppm, arising from the CH and NH protons, re-
spectively, with spin-spin coupling constants (SSCC) of 3.0–4.8
Hz. The 13C resonance peaks for the carbon atom C-4 were exhibit-
ed at 52–53 ppm, unequivocally pointing to the 3,4-dihydropyrimi-
done structure and ruling out formation of regioisomeric 2,3-
dihydropyrimidone 7.32
the mass spectra show two molecular ion peaks, with the values
[M – 1] and [M + 1], corresponding to the deprotonated ketene-
aminal form 11¢ (containing an acidic NH proton) and the protonat-
ed amidine form 11¢¢ (containing a basic imino group), respectively.
Two spots were also observed on the thin-layer chromatogram,
however, attempts at separating these tautomers by preparatory
TLC provided samples with varying ratios of the tautomeric forms.
Though structure 11¢¢ permits the existence of the cis and trans iso-
mers, only the isomer with the cis configuration of the protons H-5
and H-6 was observed in solution; it is evidently most thermody-
namically stable due to the dynamic cis–trans equilibrium that is
likely to involve the intermediate keteneaminal form 11¢. Structural
The structure of the obtained 6-amino-substituted 5-nitro-3,4-dihy-
1
dropyrimidin-2(1H)-ones 10 and 11 was supported by H and 13C
1
NMR spectroscopy as well as by APCI MS spectrometry. The H
1
NMR spectra of compounds 10 in DMSO-d6 displayed doublets at
5.6–5.7 and 8.7–8.8 ppm, originating from the CH and NH protons,
respectively, with SSCC of 3–4 Hz. 6-Aminopyrimidones 11d and
11l gave signals, arising from the NH2 group, that appeared as two
broadened singlets at 8.7–8.8 and 10.1–10.2 ppm as a result of the
intramolecular hydrogen bond formation; 6-monoalkylaminopy-
rimidones 11f,i,k,p were characterized by the broad signals from
the exocyclic NH protons at 10.1–10.6 ppm. The 1H NMR spectra
of these compounds, when measured in DMSO-d6, were indicative
of another tautomeric form, 4-imino-3,4,5,6-tetrahydropyrimidin-
2(1H)-one (11¢¢), in addition to the main form 11¢, with the content
ratio 11¢ to 11¢¢ of 45:55, 83:17, 98:2, and 91:9 for 11f,i,k and p, re-
spectively. In a CDCl3 solution, the 1H NMR spectra showed no ev-
idence of the 11¢¢ form or, in the case of 11f, suggests its lowered
content (see Table 2). The tautomerism between forms 11¢ and 11¢¢
can be regarded as a particular case of the keteneaminal–amidine
tautomerism observed previously for some acyclic compounds.33
Unlike 6-alkylaminopyrimidones, for which the keteneaminal form
predominates, their 6-arylamino counterparts tend to exist in the
amidine form (see Table 2), and it becomes the only possible form,
both in DMSO-d6 and CDCl3 solutions, for compounds 11a,b,g,
suggesting that they should be considered as 4-imino-3,4,5,6-tet-
rahydropyrimidin-2(1H)-one derivatives. The 1H NMR signals
from the protons H-5 and H-6 normally appear as slightly split mul-
tiplets. The resonance of the proton H-5 is exhibited as a doublet at
5.8–5.9 ppm with a very small SSCC of 2.0–2.5 Hz. The multiplet
at 5.5–5.6 arises from the proton H-6 and its spin coupling with the
NH proton is characterized by the SSCC of 4.4–4.5 Hz. The 13C
NMR spectrum displays signals arising from the carbon atoms H-6
and H-5 at 52–53 and 78–79 ppm, respectively.
determination of these compounds was performed by H NMR
spectroscopy with the difference NOE experiments in a DMSO-d6
solution using compound 11b as an example.
H10
H10
H1
H5
H6
N
O2N
H7
Cl
N
N
O
Me
H7
Figure 2 Structure of compound 11b
The SSCC for the protons H-5 and H-6 was found to be 2.45 Hz. On
irradiation of H-5, an NOE enhancement was detected for the pro-
ton H-6 and ortho protons H-10 and H-7 in the aryl rings, whereas
irradiation of H-6 revealed a coupling with H-5 and also with H-10
and H-1 (see Figure 2). These observations suggest that the protons
H-5 and H-6 reside on the same side of the pyrimidine ring34 and the
imino group has the E-configuration. The cis configuration is prob-
ably characteristic of all the other derivatives of structure 11¢¢.
1
The H NMR spectra of condensed pyrimidines 13 in DMSO-d6
showed characteristic doublets of the CH and NH protons at 5.4–5.6
and 9.4–11.1 ppm, respectively, with SSCC of 3–4 Hz. The 13H
NMR signal of the C-4 carbon atom was found at 52–53 ppm, as in
the case of compounds 10 and 11 (in the ketenaminal form).
The structure of compounds 14 was determined using APCI MS
The established relationships between the nature of the substituents
and the tautomeric equilibrium position are consistent with the elec-
tronic and steric structure of compounds 11. A strong electron-do-
spectrometry as well as 1H and 13C NMR spectroscopy. The molec-
1
ular ion peaks in the APCI spectra were found at [M + 1]. The H
NMR spectra displayed singlets arising from the protons H-5 and
H-1 at 5.6–6.2 and 10.8–11.0 ppm, respectively. The methylene
group of the benzyl residue in compound 14e was not spin-coupled
to the NH proton and generated a singlet at 4.6 ppm, thus corrobo-
rating the structure of 6-aryl-4-benzyliminopyrimidin-2-one. The
13C NMR signal of C-5 was observed at 90–92 ppm.
The structure of compound 14c was thoroughly studied by 1H NMR
spectroscopy and difference NOE experiments in a CDCl3, since the
prevailing tautomeric form of pyrimidines 14a–d,f which may be
either 4-arylimino-3,4-dihydropyrimidin-2(1H)-one (14c¢) or 6-
arylaminopyrimidin-2(1H)-one (14c¢¢) could not be unequivocally
determined (Scheme 4).
nor amino or alkylamino group at position
6 of 3,4-di-
hydropyrimidones, stabilizes form 11¢ due to its efficient conjuga-
tion with the nitro group at position 5 through the double bond of
the keteneaminal moiety. With an acceptor aryl substituent in the 6-
arylamino group, the conjugation of the aromatic ring with the en-
docyclic nitrogen atom, through the imino group of the amidine
moiety, becomes energetically preferable so that form 11¢¢ tends to
prevail and its content rises with increasing acceptor character of
the aryl residue (Table 2, entries 4–6 and 16–18). It is notable that
the equilibrium position is also highly dependent on the nature of
the 4-aryl substituent, since the stronger its acceptor properties, the
more stabilized is the keteneaminal form 11¢ (entries 6, 11, 13 and
Synthesis 2007, No. 6, 835–844 © Thieme Stuttgart · New York

840
V. A. Sukach et al.
PAPER
NO2
H10
Irradiation at the H-1 proton frequency give rise to an NOE en-
hancement of the signals arising from the ortho protons (H-10 and
H-14) of the 6-aryl ring. The H-5 proton was spin-coupled to both
the H-10 and H-14 protons and to the ortho protons (H-7) of the p-
anisyl residue, but not to the H-1 proton. An NOE enhancement of
the H-1 signal was also absent from the spectra recorded after irra-
diation of the H-7 protons. Taken together, this evidence suggests
that only one tautomeric form, 14c¢, exists in a solution, since oth-
erwise the NOE would manifest itself in a way that might be expect-
ed for structure 14c¢¢, i.e. an enhancement of the signal from the H-
4 protons on irradiation at H-5, but not for H-10 and H-14 on irra-
diation of H-4.
NO2
H14
H5
H14
H5
H10
H1
H7
H7
N
N
MeO
N
H4
N
O
MeO
N
N
O
Me
Me
H7
H7
14c'
14c''
Scheme 4 Structure of compound 14c
Table 5 Analytical Data for Compounds 6, 10, 11, 13 and 14a
Compd Mp (°C)b 1H NMR, DMSO-d6 (d ppm)
13C NMR, DMSO-d6 (d ppm)
MS (APCI), m/z
6a
6b
6c
6d
6e
6f
178–180
144–146
195–197
165–167
200–202
181–183
145–147
131–133
2.47 (s, 3 H), 3.29 (s, 3 H), 5.69 (d, J = Hz, 1 H), 7.21 (d, 18.20, 34.97, 52.99, 125.75, 128.20, 280 [M + 1]
J = 7.0 Hz, 2 H), 7.30 (t, J = 7.0 Hz, 1 H), 7.36 (t, J = 7.0 128.97, 140.64, 151.89, 155.46
Hz, 2 H), 8.71 (d, J = Hz, 1 H)
2.48 (s, 3 H), 3.36 (s, 3 H), 5.85 (d, J = 3.9 Hz, 1 H), 7.10– 18.10, 35.02, 49.28, 115.82, 124.77, 299 [M + 1]
7.42 (m, 4 H), 8.58 (d, J = 3.9 Hz, 1 H)
127.23, 128.72, 130.41, 151.46,
155.08, 158.85, 160.82
2.48 (s, 3 H), 3.29 (s, 3 H), 5.71 (d, J = 4.0 Hz, 1 H), 7.20 18.28, 34.85, 52.48, 122.02, 124.64, 360 [M + 1]
(d, J = 8.0 Hz, 1 H), 7.33 (t, J = 8.0 Hz, 1 H), 7.41 (s,
1 H), 7.51 (d, J = 8.0 Hz, 1 H), 8.71 (d, J = 4.0 Hz, 1 H)
127.97, 128.87, 131.08, 131.25,
143.27, 151.57, 156.14
2.48 (s, 3 H), 3.29 (s, 3 H), 5.87 (d, J = 3.6 Hz, 1 H), 7.67 18.31, 34.70, 52.32, 120.74, 123.10, 325 [M + 1]
(m, 2 H), 8.08 (s, 1 H), 7.51 (d, J = 8.0 Hz, 1 H), 8.17 (m, 127.23, 130.69, 132.28, 142.76,
1 H), 8.90 (d, J = 3.6 Hz, 1 H)
147.99, 151.40, 156.82
2.48 (s, 3 H), 3.30 (s, 3 H), 5.68 (d, J = 4.5 Hz, 1 H), 7.17 18.74, 35.28, 52.99, 121.83, 128.54, 360 [M + 1]
(d, J = 8.4 Hz, 2 H), 7.50 (d, J = 8.4 Hz, 2 H), 8.74 (d,
J = 4.5 Hz, 1 H)
132.34, 140.54, 152.15, 155.67,
156.32
2.49 (s, 3 H), 3.29 (s, 3 H), 5.85 (d, J = 4.0 Hz, 1 H), 7.52 18.35, 34.78, 52.53, 124.18, 127.27, 325 [M + 1]
(d, J = 8.5 Hz, 2 H), 8.23 (d, J = 8.5 Hz, 2 H), 8.91 (d,
J = 4.0 Hz, 1 H)
134.00, 147.28, 147.77, 151.46,
156.90
6g
6h
2.48 (s, 3 H), 3.28 (s, 3 H), 5.73 (d, J = 4.2 Hz, 1 H), 7.19 18.34, 34.75, 52.11, 126.02, 127.42, 350 [M + 1]
(dd, J1 = 8.5 Hz, J2 = 2 Hz, 1 H), 7.47 (d, J = 2 Hz, 1 H), 128.17, 130.87, 131.21, 131.44,
7.62 (d, J = 8.5 Hz, 1 H), 8.77 (d, J = 4.2 Hz, 1 H)
141.65, 151.40, 156.49
2.48 (s, 3 H), 5.03 (d, J = 15.6 Hz, 1 H), 5.18 (d, J = 15.6 19.03, 49.42, 52.79, 122.44, 125.20, 435 [M + 1]
Hz, 1 H), 5.70 (d, J = 4.8 Hz, 1 H), 7.03–7.50 (m, 9 H),
8.89 (d, J = 4.8 Hz, 1 H)
127.54, 127.85, 128.90, 129.24,
131.52, 137.66, 143.81, 151.56,
155.28
6i
152–154
2.49 (s, 3 H), 2.74 (m, 2 H), 4.05 (m, 1 H), 4.20 (m, 1 H), 18.43, 35.08, 46.71, 51.75, 125.78, 440 [M + 1]
5.68 (d, J = 4.8 Hz, 1 H), 7.05–7.29 (m, 6 H), 7.43 (s,
1 H), 7.54 (d, J = 8.4 Hz, 1 H), 8.90 (d, J = 4.8 Hz, 1 H)
126.31, 127.70, 127.93, 128.24,
128.38, 130.68, 131.04, 131.33,
137.61, 141.56, 150.62, 154.79
10a
10b
11a
194–196
231–233
155–157
1.89 (m, 2 H), 2.06 (m, 2 H), 2.96 (s, 3 H), 3.09 (m, 2 H), 24.89, 34.80, 50.72, 51.85, 112.50, 302 [M + 1]
3.69 (m, 1 H), 5.71 (d, J = 3.0 Hz, 1 H), 7.21–7.35 (m, 5 125.13, 127.40, 128.62, 141.76,
H), 8.74 (d, J = 3.0 Hz, 1 H)
152.65, 154.07
3.21 (m, 2 H), 3.36 (m, 2 H), 3.68 (m, 2 H), 3.78 (m, 2 H), 34.57, 50.29, 51.62, 65.85, 113.44, 399 [M + 1]
5.58 (d, J = 4.2 Hz, 1 H), 7.19 (d, J = 7.5 Hz, 2 H), 7.50
(d, J = 7.5 Hz, 2 H), 8.83 (d, J = 4.2 Hz, 1 H)
121.16, 127.96, 132.07, 141.70,
154.19, 155.47
3.17 (s, 3 H), 5.26 (m, 1 H), 5.59 (s, 1 H), 6.10 (d, J = 7.2 28.93, 52.60, 78.64, 119.53, 123.73, 325 [M + 1]
Hz, 2 H), 7.02 (t, J = 7.2 Hz, 1 H), 7.15–7.42 (m, 7 H),
8.47 (d, J = 4.0 Hz, 1 H)
125.78, 128.56, 129.00, 129.08,
135.99, 144.65, 146.84, 152.20
Synthesis 2007, No. 6, 835–844 © Thieme Stuttgart · New York

PAPER
Synthesis of 5-Nitro-3,4-dihydropyrimidin-2(1H)-one Derivatives
841
Table 5 Analytical Data for Compounds 6, 10, 11, 13 and 14a (continued)
Compd Mp (°C)b
1H NMR, DMSO-d6 (d ppm)
13C NMR, DMSO-d6 (d ppm)
MS (APCI), m/z
11b
196–198
3.19 (s, 3 H), 5.27 (m, 1 H), 5.72 (d, J = 2.45 Hz, 1 H),
6.09 (d, J = 8.4 Hz, 2 H), 7.17 (d, J = 8.4 Hz, 2 H), 7.26
(d, J = 6.6 Hz, 2 H), 7.41 (m, 3 H), 8.51 (d, J = 4.5 Hz,
1 H)
28.97, 52.44, 78.69, 121.36, 125.64, 360 [M + 1]
127.93, 118.55, 128.96, 128.99,
135.78, 145.29, 145.75, 152.03
11c
164–166
2.72 (s, 0.57 H), 3.19 (s, 3 H), 3.72 (s, 3 H), 3.80 (s,
0.57 H), 5.28 (m, 1 H), 5.66 (s, 1 H), 5.75 (d, J = 4.0 Hz,
0.19 H), 6.09 (d, J = 8.4 Hz, 2 H), 6.76 (d, J = 8.4 Hz,
2 H), 7.00 (d, J = 8.8 Hz, 0.38 H), 7.18 (d, J = 8.8 Hz,
0.38 H), 7.20–7.44 (m, 5.95 H), 8.44 (s, 1 H), 8.72 (d,
J = 4.0 Hz, 0.19 H), 11.42 (s, 0.19 H)
–
355 [M + 1]
353 [M – 1]
[2.77 (s, 0.45 H), 3.37 (s, 3 H), 3.71 (s, 3 H), 3.79 (s,
0.45 H), 5.32 (m, 2 H), 6.00 (d, J = 4.4 Hz, 0.15 H), 6.11
(d, J = 8.8 Hz, 2 H), 6.68 (m, 3.15 H), 6.90 (d, J = 8.4 Hz,
0.30 H), 7.03 (d, J = 8.4 Hz, 0.30 H), 7.15 (d, J = 8.0 Hz,
2 H), 7.27–7.40 (m, 3.75 H), 11.73 (s, 0.15 H)]c
11d
11e
252–254
167–169
3.22 (s, 3 H), 5.64 (d, J = 3.0 Hz, 1 H), 7.06–7.14 (m,
2 H), 7.23–7.32 (m, 2 H), 8.48 (d, J = 3.0 Hz, 1 H), 8.73 128.79, 129.36, 129.60, 149.79,
(br s, 1 H), 10.28 (br s, 1 H)
29.09, 47.88, 115.43, 124.29,
265 [M – 1]
153.48, 159.08, 161.03
2.73 (s, 0.51 H), 3.20 (s, 3 H), 5.28 (m, 1 H), 5.71–5.74
(m, 1.17 H), 6.18 (d, J = 7.2 Hz, 2 H), 7.06 (t, J = 7.4 Hz,
1 H), 7.19–7.53 (m, 7.53 H), 8.54 (d, J = 3.6 Hz, 1 H),
8.81 (d, J = 4.0 Hz, 0.17 H), 11.12 (s, 0.17 H)
–
405 [M + 1]
403 [M – 1]
11f
180–182
186–188
4.52–4.60 (m, 3.5 H), 5.09–5.14 (m, 1.5 H), 5.32 (m,
0.25 H), 5.64 (s, 0.25 H), 5.90 (d, J = 3.0 Hz, 1 H), 6.72–
7.31 (m, 17.75 H), 10.42 (br s, 1 H)c
–
495 [M + 1]
493 [M – 1]
11g
5.03 (m, 2 H), 5.31 (m, 1 H), 5.78 (d, J = 2.4 Hz, 1 H),
45.17, 52.26, 78.75, 120.06, 122.79, 481 [M + 1]
6.14 (d, J = 7.5 Hz, 2 H), 7.04 (t, J = 6.6 Hz, 1 H), 7.21– 124.50, 125.53, 127.35, 127.91,
7.38 (m, 9 H), 7.47 (s, 1 H), 7.55 (d, J = 8.1 Hz, 1 H), 8.63 128.57, 129.49, 129.71, 131.60,
(d, J = 4.0 Hz, 1 H)
132.07, 137.90, 139.06, 144.46,
147.08, 152.41
11h
11i
171–173
176–178
2.80 (s, 1.14 H), 3.40 (s, 3 H), 3.76 (s, 3 H), 3.82 (1.14 H),
–
435 [M + 1]
433 [M – 1]
5.34 (m, 2 H), 5.99 (d, J = 0.38 H)c
3.16 (s, 0.6 H), 3.22 (s, 3 H), 4.52 (d, J = 15.2 Hz, 0.2 H),
4.60 (d, J = 15.2 Hz, 0.2 H), 4.67 (d, J = 13.6 Hz, 0.2 H),
4.81 (d, J = 13.6 Hz, 0.2 H), 5.57 (s, 0.2 H), 5.76 (d,
J = 4.4 Hz, 1 H), 6.93 (m, 0.2 H), 7.11 (m, 0.4 H), 7.30–
7.68 (m, 8.4 H), 8.03–8.19 (m, 2.4 H), 8.47 (s, 0.2 H),
8.82 (d, J = 4.4 Hz, 1 H), 10.33 (br s, 1 H)
–
384 [M + 1]
382 [M – 1]
11j
236–238
2.74 (s, 3 H), 3.24 (s, 2.43 H), 3.73 (s, 2.43 H), 3.81 (s,
3 H), 5.43–5.46 (m, 1 H), 5.90–5.93 (m, 1.81 H), 6.18 (d,
J = 8.1 Hz, 1.62 H), 6.76 (d, J = 8.1 Hz, 1.62 H), 7.00 (d,
J = 7.8 Hz, 2 H), 7.19 (d, J = 8.0 Hz, 1.62 H), 7.42–7.53
(m, 3.62 H), 8.15–8.27 (m, 3.62 H), 8.54 (d, J = 2.7 Hz,
0.81 H), 8.79 (d, J = 2.4 Hz, 1 H), 11.38 (s, 0.81 H)
–
400 [M + 1]
398 [M – 1]
11k
11l
221–223
263–265
3.20 (s, 3 H), 3.23 (s, 3 H), 5.77 (d, J = 4.0 Hz, 1 H), 7.63 33.49, 34.46, 51.49, 109.21, 121.10, 306 [M – 1]
(m, 2 H), 8.08 (s, 1 H), 8.12 (s, 1 H), 8.77 (d, J = 4.0 Hz, 123.16, 130.89, 132.77, 144.48,
1 H), 10.13 (br s, 1 H)
148.45, 153.15, 156.10
3.21 (s, 3 H), 5.62 (d, J = 2.7 Hz, 1 H), 7.50 (d, J = 8.1 Hz, 29.42, 51.65, 105.33, 123.78,
2 H), 8.15 (d, J = 8.1 Hz, 2 H), 8.67 (d, J = 2.7 Hz, 1 H), 127.85, 146.96, 149.45, 150.07,
292 [M – 1]
8.79 (br s, 1 H), 10.19 (br s, 1 H)
153.51
Synthesis 2007, No. 6, 835–844 © Thieme Stuttgart · New York

842
V. A. Sukach et al.
PAPER
Table 5 Analytical Data for Compounds 6, 10, 11, 13 and 14a (continued)
Compd Mp (°C)b
1H NMR, DMSO-d6 (d ppm)
13C NMR, DMSO-d6 (d ppm)
MS (APCI), m/z
11m
207–209
2.76 (s, 0.96 H), 3.22 (s, 3 H), 5.44 (m, 1 H), 5.82 (d,
J = 4.4 Hz, 1 H), 5.88 (d, J = 4.8 Hz, 0.32 H), 6.23 (d,
J = 7.6 Hz, 2 H), 7.06 (t, J = 7.6 Hz, 1 H), 7.15–7.30 (m,
3.28 H), 7.42 (t, J = 8.0 Hz, 0.32 H), 7.55–7.62 (m,
2.64 H), 8.25 (d, J = 8.0 Hz, 0.32 H), 8.31 (d, J = 8.8 Hz,
2 H), 8.64 (d, J = 4.4 Hz, 1 H), 8.92 (d, J = 4.8 Hz,
0.32 H), 11.12 (s, 0.32 H)
–
370 [M + 1]
368 [M – 1]
11n
11o
218–220
203–205
2.8 (s, 0.36 H), 3.20 (s, 3 H), 5.43 (m, 1 H), 5.86 (d,
J = 2.0 Hz, 0.12 H), 5.93 (s, 1 H), 6.22 (d, J = 8.0 Hz,
2 H), 7.25 (m, 2.48 H), 7.40 (d, J = 8.4 Hz, 0.12 H), 8.26
(m, 2.24 H), 8.67 (d. J = 4.0 Hz, 1 H), 8.90 (d, J = 2.0 Hz,
0.12 H), 10.88 (s, 0.12 H)
–
–
405 [M + 1]
403 [M – 1]
2.72 (s, 1.38 H), 3.20 (s, 3 H), 3.72 (3 H), 3.80 (s, 1.38 H),
5.43 (m, 1 H), 5.87 (m, 1.46 H), 6.17 (d, J = 8.1 Hz, 2 H),
6.78 (d, J = 8.1 Hz, 2 H), 6.99 (d, J = 8.1 Hz, 0.92 H), 7.18
(d, J = 8.1 Hz, 0.92 H), 7.54–7.60 (m, 2.92 H), 8.22 (d,
J = 7.8 Hz, 0.92 H), 8.28 (d, J = 7.8 Hz, 2 H), 8.59 (d,
J = 2.5 Hz, 1 H), 8.85 (d, J = 3.3 Hz, 0.46 H), 11.38 (s,
0.46 H)
400 [M + 1]
398 [M – 1]
11p
11q
180–182
199–201
3.33 (s, 3 H), 4.64 (dd, J1 = 5.2 Hz, J2 = 12.8 Hz, 2 H),
5.89 (d, J = 4.0 Hz, 1 H), 6.42 (d, J = 4.0 Hz, 1 H), 7.05
(d, J = 8.4 Hz, 1 H), 7.15–7.39 (m, 7 H), 10.63 (br s, 1 H)c
–
–
409 [M + 1]
407 [M – 1]
2.27 (s, 3 H), 2.33 (s, 1.11 H), 2.70 (s, 1.11 H), 3.20 (s,
3 H), 5.26 (m, 1 H), 5.74 (d, J = 3.3 Hz, 0.37 H), 5.79 (s,
1 H), 6.12 (d, J = 8.1 Hz, 2 H), 7.05 (d, J = 8.1 Hz, 2 H),
7.10–7.26 (m, 2.85 H), 7.47–7.65 (m, 2.74 H), 8.56 (d,
J = 3.9 Hz, 1 H), 8.81 (d, J = 3.3 Hz, 0.37 H), 11.23 (s,
0.37 H)
409 [M + 1]
407 [M – 1]
13a
13b
243–245
239–241
3.75–3.93 (m, 4 H), 5.43 (d, J = 3.0 Hz, 1 H), 7.27–7.30 42.89, 43.35, 53.49, 103.53, 126.43, 261 [M + 1]
(m, 5 H), 8.29 (d, J = 3.0 Hz, 1 H), 9.42 (br s, 1 H)
127.56, 128.34, 142.55, 149.98,
151.81
2.01 (m, 2 H), 3.48–3.81 (m, 4 H), 5.62 (d, J = 3.3 Hz,
18.96, 38.78, 39.17, 51.58, 104.41, 320 [M + 1]
1 H), 7.61 (t, J = 7.5 Hz, 1 H), 7.69 (d, J = 7.5 Hz, 1 H), 121.36, 122.58, 130.15, 132.92,
8.10–8.14 (m, 2 H), 8.64 (d, J = 3.3 Hz, 1 H), 11.06 (br s, 144.40, 147.67, 149.56, 150.52
1 H)
13c
13d
14a
233–235
258–260
216–218
1.91 (m, 2 H), 3.45–3.83 (m, 4 H), 5.61 (d, J = 2.4 Hz,
1 H), 7.54 (d, J = 8.0 Hz, 2 H), 8.15 (d, J = 8.0 Hz, 2 H), 124.19, 128.40, 147.38, 150.00,
8.63 (d, J = 2.4 Hz, 1 H), 11.04 (s, 1 H)
19.45, 39.32, 40.36, 52.20, 104.90, 320 [M + 1]
150.11, 150.97
3.78–3.96 (m, 4 H), 5.48 (d, J = 2.7 Hz, 1 H), 7.26 (d,
J = 8.4 Hz, 1 H), 7.49 (s, 1 H), 7.53 (d, J = 8.4 Hz, 1 H), 128.74, 130.13, 130.59, 130.86,
8.32 (d, J = 2.7 Hz, 1 H), 9.49 (br s, 1 H) 143.53, 149.52, 151.66
42.89, 43.40, 52.82, 102.63, 126.88, 331 [M + 1]
5.57 (s, 1 H), 6.83 (d, J = 7.2 Hz, 2 H), 7.00 (t, J = 7.2 Hz, 28.00, 90.92, 121.60, 122.25,
1 H), 7.30–7.48 (m, 7 H), 10.95 (s, 1 H)
278 [M + 1]
434 [M + 1]
126.41, 128.81, 129.14, 130.58,
132.04, 146.46, 149.85, 150.84,
151.45
14b
14c
252–254
238–240
5.23 (s, 2 H), 5.60 (s, 1 H), 6.71 (d, J = 7.5 Hz, 2 H), 6.97 43.30, 91.74, 121.34, 121.79,
(t, J = 7.2 Hz, 1 H), 7.25–7.60 (m, 9 H), 7.59 (d, J = 7.2
Hz, 1 H), 7.70 (s, 1 H), 10.99 (s, 1 H)
122.30, 125.59, 126.68, 127.54,
128.00, 129.02, 129.13, 130.74,
133.16, 134.24, 137.52, 145.30,
149.23, 149.82, 151.11
3.47 (s, 3 H), 3.81 (s, 3 H), 5.99 (s, 1 H), 6.79 (d, J = 8.7 28.19, 55.06, 92.11, 114.44, 121.36, 353 [M + 1]
Hz, 2 H), 6.89 (d, J = 8.7 Hz, 2 H), 7.63 (t, J = 8.1 Hz, 122.72, 124.83, 130.29, 132.91,
1 H), 7.86 (d, J = 7.5 Hz, 1 H), 8.31 (d, J = 7.5 Hz, 1 H), 147.77, 151.79, 155.15 (other sig-
8.59 (s, 1 H), 11.02 (s, 1 H)c
nals absent)
Synthesis 2007, No. 6, 835–844 © Thieme Stuttgart · New York

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Synthesis of 5-Nitro-3,4-dihydropyrimidin-2(1H)-one Derivatives
843
Table 5 Analytical Data for Compounds 6, 10, 11, 13 and 14a (continued)
Compd Mp (°C)b 1H NMR, DMSO-d6 (d ppm)
3.30 (s, 3 H), 3.74 (s, 3 H), 5.78 (s, 1 H), 6.84 (d, J = 8.1 28.22, 55.07, 114.45, 122.82,
13C NMR, DMSO-d6 (d ppm)
MS (APCI), m/z
353 [M + 1]
14d
270–272
Hz, 2 H), 6.90 (d, J = 8.1 Hz, 2 H), 7.82 (d, J = 8.4 Hz,
2 H), 8.23 (d, J = 8.4 Hz, 2 H), 10.85 (br s, 1 H)
123.72, 128.00, 148.28, 151.66,
155.24 (other signals absent)
14e
217–219
3.42 (s, 3 H), 4.60 (s, 2 H), 6.21 (s, 1 H), 7.23–7.41 (m,
5 H), 7.59 (d, J = 8.7 Hz, 1 H), 7.87 (d, J = 8.7 Hz, 1 H), 127.06, 128.36, 128.60, 130.49,
29.31, 45.21, 82.54, 126.87, 126.93, 362 [M + 1]
8.10 (s, 1 H), 8.13 (s, 1 H)
131.29, 132.90, 137.87, 138.14,
155.66, 157.49, 162.28
14f
263–265
2.28 (s, 3 H), 3.32 (s, 3 H), 5.62 (s, 1 H), 6.66 (d, J = 7.2 20.27, 27.99, 91.23, 121.52, 126.62, 362 [M + 1]
Hz, 2 H), 7.06 (d, J = 7.2 Hz, 2 H), 7.39 (d, J = 7.8 Hz, 128.36, 129.49, 130.73, 131.20,
1 H), 7.59 (d, J = 7.8 Hz, 1 H), 7.74 (s, 1 H), 10.94 (s, 1 H) 131.43, 132.87, 132.97, 143.62,
146.04, 150.75, 151.43
a Satisfactory microanalysis obtained: C 0.30, H 0.08, N 0.16.
b Melting points are uncorrected.
c Recorded in CDCl3.
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