An efficient synthesis of 2,3-dihydro-1H-pyrimido[1,2-a]quinoxaline 6-oxides

Article abstract of DOI:10.1055/s-2002-35980

5-Substituted 2,3-dihydro-1H-pyrimido[1,2-a]quinoxaline 6-oxides 1a-f were synthesized by ring closure of N-acyl-N′-(o-nitroaryl)-1,3-propanediamines 2 with ethyl polyphosphate (PPE) or trimethylsilyl polyphosphate (PPSE) to the corresponding 2-substituted 1-(o-nitroaryl)-1,4,5,6-tetrahydropyrimidines 3, followed by spontaneous heterocyclization. The method was extended to the synthesis of the homologous 6-aryl- 1,2,3,4-tetrahydro- 1,3-diazepino[1,2-a]quinoxaline 7-oxide (1g).

Full text of DOI:10.1055/s-2002-35980

PAPER
2687
An Efficient Synthesis of 2,3-Dihydro-1H-pyrimido[1,2-a]quinoxaline
6-Oxides
S
ynthesis of 2,3-Dihyd
a
ro-1
H
-pyri
r
mido[1,2
í
-
a
]qui
a
noxaline
6
-Oxide
B
s
. García, Liliana R. Orelli, María L. Magri, Isabel A. Perillo*
Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Junín 956 (1113) Buenos Aires, Argentina
Fax +54(1)149648250; E-mail: iperillo@ffyb.uba.ar
Received 15 July 2002; revised 26 September 2002
erocycles. To our knowledge, no synthetic procedure has
been reported for the preparation of 5-alkyl derivatives.
Abstract : 5-Substituted 2,3-dihydro-1H-pyrimido[1,2-a]quinoxa-
line 6-oxides 1a–f were synthesized by ring closure of N-acyl-N -(o-
nitroaryl)-1,3-propanediamines 2 with ethyl polyphosphate (PPE)
or trimethylsilyl polyphosphate (PPSE) to the corresponding 2-sub-
stituted 1-(o-nitroaryl)-1,4,5,6-tetrahydropyrimidines 3, followed
by spontaneous heterocyclization. The method was extended to the
synthesis of the homologous 6-aryl-1,2,3,4-tetrahydro-1,3-diazepi-
no[1,2-a]quinoxaline 7-oxide (1g).
The present paper describes an improved approach to the
synthesis of 5-aryl derivatives 1a–d from easily available
starting materials with high yields. 5-Arylalkyl and alkyl
derivatives 1e,f, respectively, were prepared by the same
procedure. The procedure was extended to the synthesis
of the homologous 1,2,3,4-tetrahydro-6-phenyl-1,3-dia-
zepino[1,2-a]quinoxaline 7-oxide (1g), a condensed nitro-
gen heterocycle which, to our knowledge, has not been
previously described in the literature.
Key words: heterocycles, nitrogen, cyclizations, antibiotics, antitu-
mor agents
The synthetic procedure for the 5-substituted 2,3-dihydro-
1H-pyrimido[1,2-a]quinoxaline 6-oxides 1a–f is dis-
played in Scheme 1. The starting materials, N-acyl-N -(o-
nitroaryl)trimethylenediamines 2 (n = 1), are easily syn-
thesized by acylation of the corresponding N-(o-nitrophe-
nyl)-1,3-propanediamines. Treatment of arylacetyl
derivatives 2a–d with ethyl polyphosphate (PPE) leads to
unstable 2-benzyl-1-(o-nitrophenyl)-1,4,5,6-tetrahydro-
pyrimidines 3a–d which were detected by TLC but could
not be isolated as pure compounds due to spontaneous in
situ cyclization leading to N-oxides 1 (Table 1). Heterocy-
clization of intermediates 3a–d was achieved in ca. 24
hours and was easily monitored by TLC.
2,3-Dihydro-1H-pyrimido[1,2-a]quinoxaline
6-oxides
are of interest due to the biological activity shown by
some of their derivatives. Some suitably substituted deriv-
atives possess antineoplastic activity,1 specially against
hypoxic tumors. Other pyrimidoquinoxaline 6-oxides
have been employed as antiamoebic2 and antianaerobic
agents.3
The reported synthetic procedure for 5-aryl-2,3-dihydro-
1H-pyrimido[1,2-a]quinoxaline 6-oxides2,3 involves a
displacement-cyclization reaction of 2-benzyl-1,4,5,6-tet-
rahydropyrimidines with o-nitrohalobenzenes and leads
in general to poor yields (30% or less) of the desired het-
Scheme 1
Synthesis 2002, No. 18, Print: 19 12 2002.
Art Id.1437-210X,E;2002,0,18,2687,2690,ftx,en;M03002SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

2688
M. B. García et al.
PAPER
From a mechanistic point of view, it can be considered dine with o-halonitrobenzenes leading to quinoxaline N-
that the reaction results from an initial nucleophilic attack oxides.
of the benzylic carbon of the amidine 3 (or its tautomeric
Application of our procedure to alkanoyl derivatives 2e,f
form 3 ) on the nitro group, followed by proton transfer
leads to the corresponding N-oxides 1e,f (Table 1). Treat-
and dehydration (Scheme 2). A similar mechanism was
ment of such precursors with trimethylsilyl polyphos-
proposed by Strauss4 for the reaction of phenylacetami-
phate (PPSE)5 afforded the corresponding 1,4,5,6-
tetrahydropyrimidines 3e,f, which were isolated and char-
acterized spectroscopically (1H NMR and mass spectrom-
N
N
N
N
etry). In contrast to 2-arylmethyl derivatives 3a–d,
disappearance of the amidines in this case takes several
days for completion. The observed difference in heterocy-
clization rates can be related to the lower acidity of the
methylene group adjacent to the amidine moiety in com-
pounds 3e,f when compared to the 2-benzyl derivatives
3a–d. The requirement of a relatively acidic -methylene
was also pointed out by Strauss4 to account for the lack of
reactivity of propionamidine towards 2,4-dinitrofluoro-
benzene. Due to the low heterocyclization rates of com-
pounds 3e,f, conversion to the corresponding N-oxides is
accompanied to some extent by amidine hydrolysis. This
collateral reaction regenerates the corresponding amino
amides 2e,f, thus diminishing reaction yields. In fact,
when N-acetyl-N -(o-nitrophenyl)-1,3-propanediamine
(2, n = 1, R = H) was treated with PPSE in order to obtain
H
CH2
CH
N
O
O
N
O
O
3'a
3a
N
N
N
N
H2O
N
O
H
OH
N
O
1a
Scheme 2
Table 1 Compounds 1a–g Prepared
Producta Mp
(°C)
MS
Yield (%)
91
1H NMR (CDCl3/TMS)b
, J (Hz)
(m/z, M.+)
1a
209–210
277
8.37 (dd, 1 Harom, J1 = 8.2, J2 = 1.5), 7.40–7.59 (m, 6 Harom), 7.16 (dt, 1 Harom,
(EtOH)
J1 = 8.2, J2 = 1.0), 7.07 (d, 1 Harom, J = 8.2), 3.88 (t, 2 H, J = 6.2, CH2N), 3.58
(t, 2 H, J = 5.4, CH2N), 2.02–2.06 (m, 2 H, CH2CH2CH2)
1b
231–233
(EtOH)
311, 313
86
78
85
49
8.36 (dd, 1 Harom, J1 = 7.8, J2 = 1.5), 7.57 (dd, 2 Harom, J1 = 8.8, J2 = 2.1), 7.51
(dt, 1 Harom, J1 = 8.5, J2 = 1.5), 7.44 (dd, 2 Harom, J1 = 8.8, J2 = 2.1), 7.15–7.20
(m, 1arom H), 7.07 (d, 1 Harom, J = 8.5), 3.88 (t, 2 H, J = 6.2, CH2N), 3.58 (t, 2
H, J = 5.5, CH2N), 2.00–2.08 (m, 2 H,CH2CH2CH2)
1c
1d
1e
206–208
(EtOH)
322
307
291
8.30–8.36 (m, 3 Harom), 7.80 (dd, 2 Harom, J1 = 6.9, J2 = 2.0), 7.55 (dt, 1 Harom
,
J1 = 7.2, J2 = 1.5), 7.20 (dt, 1 Harom, J1 = 8.4, J2 = 1.0), 7.11 (d, 1 Harom
,
J = 8.4), 3.91 (t, 2 H, J = 6.2, CH2N), 3.57 (t, 2 H, J = 5.5, CH2N), 2.05–2.09
(m, 2 H, CH2CH2CH2)
184–186
(EtOH)
8.38 (dd, 1 Harom, J1 = 8.2, J2 = 1.5), 7.61 (d, 2 Harom, J = 9.0), 7.49 (dt, 1 Harom,
J1 = 7.8, J2 = 1.5), 7.14–7.19 (m, 1 Harom), 7.06 (d, 1 Harom, J = 7.8), 6.98 (d, 2
Harom, J = 9.0), 3.88 (t, 2 H, J = 5.5, CH2N), 3.83 (s, 3 H, CH3O), 3.60 (t, 2 H,
J = 5.5, CH2N), 2.01–2.09 (m, 2 H, CH2CH2CH2)
149–150
(EtOH)
8.31 (dd, 1 Harom, J1 = 6.9, J2 = 1.5), 7.54 (d, 2 Harom, J = 8.0), 7.43 (dt, 1 Harom,
J1 = 7.0, J2 = 1.5), 7.11–7.28 (m, 4 Harom), 6.99 (d, 1 Harom, J = 8.2), 4.43 (s, 2
H, CH2C6H5), 3.83 (t, 2 H, J = 6.2, CH2N), 3.70 (t, 2 H, J = 4.9, CH2N), 2.05–
2.11 (m, 2 H,CH2CH2CH2)
1f
179–180
(EtOH)
215
48
25
8.35 (dd, 1 Harom, J1 = 8.2, J2 = 1.5), 7.45 (dt, 1 Harom, J1 = 7.8, J2 = 1.5), 7.13–
7.19 (m, 1 Harom), 7.03 (d, 1 Harom, J = 7.8), 3.84 (t, 2 H, J = 6.2, CH2N), 3.65
(t, 2 H, J = 5.5, CH2N), 2.54 (s, 3 H, CH3), 2.02–2.06 (m, 2 H, CH2CH2CH2)
1g
oil
325, 327
8.30 (dd, 1 Harom, J1 = 8.3, J2 = 1.3), 7.67 (dd, 2 Harom, J1 = 8.3, J2 = 1.7), 7.51–
7.54 (m, 1 Harom), 7.45 (dd, 2 Harom, J1 = 8.3, J2 = 1.7), 7.16 (t, 1 Harom, J = 8.2),
7.08 (d, 1 Harom, J = 8.2), 4.08 (t, J = 5.6, CH2N), 3.87 (t, 2 H, J = 5.7, CH2N),
2.18–2.21 (m, 2 H, CH2CH2CH2CH2), 2.01–2.04 (m, 2 H, CH2CH2CH2CH2)
a Satisfactory microanalyses obtained: C 0.07, H 0.06, N 0.08.
b Recorded at 300 MHz, 25 °C.
Synthesis 2002, No. 18, 2687–2690 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of 2,3-Dihydro-1H-pyrimido[1,2-a]quinoxaline 6-Oxides
2689
CH2N), 3.29 (t, 2 H, J = 6.7 Hz, CH2N), 1.88 (pent, 2 H, J = 6.7 Hz,
CH2CH2CH2).
MS: m/z = 347/349 (M.+).
the 5-unsubstituted pyrimidinoquinoxaline N-oxide (1,
n = 1, R = H), the intermediate amidine (3, n = 1, R = H),
regenerated the acyl derivative on standing.
Anal. Calcd for C17H18ClN3O3: C, 58.71; H, 5.22; Cl, 10.19; N,
12.08. Found: C, 58.74; H, 5.25; Cl, 10.11; N, 12.02.
In order to explore the applicability of the method to the
synthesis of novel amidinoquinoxalines, N-(p-chlorophe-
nyl)acetyl-N -(o-nitroaryl)-1,4-diaminobutane (2g) was
treated with PPE, yielding the corresponding 1,2-disubsti-
tuted-1,3-diazepine 3g. Heterocyclization of amidine 3g
in chloroform for 36 hours afforded the corresponding N-
oxide 1g in modest yields (Table 1).
N-(p-Nitrophenylacetyl)-N -(o-nitrophenyl)-1,3-propane-
diamine (2c)
Yield: 71%; mp 128–129 °C (MeOH–H2O).
1H NMR: = 8.13–8.19 (m, 3 Harom), 8.06 (br s, 1 H, NHCO), 7.40–
7.43 (m, 1 Harom), 7.45 (d, 2 Harom, J = 8.7 Hz), 6.78 (d, 1 Harom
,
J = 8.7 Hz), 6.65 (t, 1 Harom, J = 8.2 Hz), 5.80 (br s, 1 H, NHAr),
3.66 (s, 2 H, CH2CO), 3.42 (q, 2 H, J = 6.4 Hz, CH2N), 3.30–3.36
(m, 2 H, CH2N), 1.88–1.97 (m, 2 H, CH2CH2CH2).
MS: m/z = 358 (M.+).
Melting points were taken on a Büchi capillary apparatus
and are uncorrected. 1H NMR spectra were recorded on a
Bruker 300 MHz spectrometer with CDCl3 as the solvent.
Standard concentration of the samples was 20 mg/mL.
Chemical shifts are reported in ppm ( ) relative to TMS as
an internal standard. MS (EI) were recorded with a GC-
MS Shimadzu QP-1000 spectrometer operating at 20 eV.
TLC analyses were carried out on silica gel 60 F254 sheets.
Column chromatography was performed on silica gel 60
(0.063–0.200 mm). Flash chromatography was performed
Anal. Calcd for C17H18N4O5: C, 56.98; H, 5.06; N, 15.63. Found: C,
56.92; H, 5.10; N, 15.58.
N-(p-Methoxyphenylacetyl)-N -(o-nitrophenyl)-1,3-propane-
diamine (2d)
Yield: 70%; mp 92–94 °C (EtOH–H2O).
1H NMR: = 8.16 (dd, 1 Harom, J1 = 8.5, J2 = 1.5 Hz), 8.03 (br s, 1
H, NHCO), 7.39–7.44 (m, 1 Harom), 7.16 (dd, 2 Harom, J1 = 6.6,
on silica gel 60 (0.040–0.063 mm), with typically 30–50 J2 = 2.1 Hz), 6.87 (dd, 2 Harom, J1 = 6.6, J2 = 2.1 Hz,), 6.76 (d, 1
Harom, J = 8.7 Hz), 6.62–6.67 (m, 1 Harom), 5.54 (br s, 1 H, NHAr),
3.80 (s, 3 H, OCH3), 3.53 (s, 2 H, CH2CO), 3.36 (q, 2 H, J = 6.7 Hz,
CH2N), 3.28 (q, 2 H, J = 6.9 Hz, CH2N), 1.81–1.90 (m, 2 H,
CH2CH2CH2).
g of stationary phase per gram of substance. Reagents,
solvents and starting materials were purchased from stan-
dard sources and purified according to literature proce-
dures.
MS: m/z = 343 (M.+).
N-(o-Nitrophenyl)-1,3-propanediamine6 and N-(o-nitro-
Anal. Calcd for C18H21N3O4: C, 62.96; H, 6.16; N, 12.24. Found: C,
63.00; H, 6.19; N, 12.17.
phenyl)-1,4-butanediamine7 were described in the litera-
ture.
N-(o-Nitrophenyl)-N -(3-phenylpropionyl)-1,3-propane-
diamine (2e)
Yield: 65%; mp 98–99 °C (EtOH–H2O).
1H NMR: = 8.16 (dd, 1 Harom, J1 = 8.6, J2 = 1.5 Hz), 8.02 (br s, 1
N-Acyl-N -(o-nitrophenyl)-1,n-(alkane)diamines 2; General
Procedure
The acyl chloride (10 mmol) was added to a CHCl3 solution of the
corresponding N-(o-nitrophenyl)-1,n-diamine (10 mmol), followed
H, NHCO), 7.40–7.45 (m, 1 Harom), 7.15–7.29 (m, 5 Harom), 6.78 (d,
by aq 4% NaOH (10 mL). The mixture was shaken for 15 min, after
1 Harom, J = 7.9 Hz), 6.62–6.67 (m, 1 Harom), 5.55 (br s, 1 H, NHAr),
which the organic layer was separated, washed with H2O, dried
(Na2SO4) and filtered. The solvent was removed in vacuo. The
crude product was purified by flash chromatography on silica gel
using mixtures of CHCl3–EtOAc as eluent.
3.35 (q, 2 H, J = 6.5 Hz, CH2N), 3.20 (q, 2 H, J = 6.9 Hz, CH2N),
2.97 (t, 2 H, J = 7.6 Hz, CH2C6H5), 2.49 (t, 2 H, J = 7.6 Hz,
CH2CO), 1.81–1.85 (m, 2 H, CH2CH2CH2).
MS: m/z = 327 (M.+).
N-(o-Nitrophenyl)-N -phenylacetyl-1,3-propanediamine (2a)
Anal. Calcd for C18H21N3O3: C, 66.04; H, 6.47; N, 12.84. Found: C,
Yield: 79%; mp 79–81 °C (EtOH–H2O).
66.10; H, 6.15; N, 12.78.
1H NMR: = 8.15 (dd, 1 Harom, J1 = 8.7, J2 = 1.6 Hz), 8.03 (br s, 1
H, NHCO), 7.40–7.43 (m, 1 Harom), 7.23–7.40 (m, 5 Harom), 6.75 (d,
1 Harom, J = 8.1 Hz), 6.63 (dt, 1 Harom, J1 = 8.7, J2 = 1.2 Hz), 5.57 (br
s, 1 H, NHAr), 3.59 (s, 2 H, CH2CO), 3.35 (q, 2 H, J = 6.9 Hz,
CH2N), 3.27 (q, 2 H, J = 6.9 Hz, CH2N), 1.85 (pent, 2 H, J = 6.9 Hz,
CH2CH2CH2).
N-(o-Nitrophenyl)-N -propionyl-1,3-propanediamine (2f)
Yield: 83%; mp 63–65 °C (EtOH–H2O).
1H NMR: = 8.17 (dd, 1 Harom, J1 = 8.6, J2 = 1.5 Hz), 8.09 (br s, 1
H, NHCO), 7.44 (dt, 1 Harom, J1 = 7.8, J2 = 1.5 Hz), 6.84 (d, 1 Harom
J = 8.3 Hz), 6.63–6.68 (m, 1 Harom), 5.61 (br s, 1 H, NHAr), 3.33–
3.45 (m, 4 H, CH2N), 2.23 (q, 2 H, J = 7.5 Hz, CH2CH3), 1.92–1.97
(m, 2 H, CH2CH2CH2), 1.16 (t, 3 H, J = 7.5 Hz, CH2CH3).
MS: m/z = 251 (M.+).
,
MS: m/z = 313 (M.+).
Anal. Calcd for C17H19N3O3: C, 65.16; H, 6.11; N, 13.41. Found: C,
65.20; H, 6.15; N, 13.37.
Anal. Calcd for C12H17N3O3: C, 57.36; H, 6.82; N, 16.72. Found: C,
57.42; H, 6.87; N, 16.68.
N-(p-Chlorophenylacetyl)-N -(o-nitrophenyl)-1,3-propane-
diamine (2b)
Yield: 99%; mp 107–109 °C (EtOH–H2O).
N-(p-Chlorophenylacetyl)-N -(o-nitrophenyl)-1,4-butane-
diamine (2g)
Yield: 92%; mp 106–108 °C (EtOH–H2O).
1H NMR: = 8.16 (dd, 1 Harom, J1 = 8.6, J2 = 1.5 Hz), 8.03 (br s, 1
H, NHCO), 7.40–7.43 (m, 1 Harom), 7.35 (dd, 2 Harom, J1 = 6.4,
J2 = 2.0 Hz), 7.30 (dd, 2 H, J1 = 6.4, J2 = 2.0 Hz), 6.78 (d, 1 Harom
1H NMR: = 8.16 (dd, 1 Harom, J1 = 8.6, J2 = 1.5 Hz), 8.04 (br s, 1
H, NHCO), 7.40–7.47 (m, 1 Harom), 7.31 (dd, 2 Harom, J1 = 6.4,
J2 = 2.0 Hz), 7.19 (dd, 2 Harom, J1 = 6.4, J2 = 2.0 Hz), 6.77 (d, 1
Harom, J = 8.7 Hz), 6.65 (dt, 1 Harom, J1 = 8.6, J2 = 1.3 Hz), 5.52 (br
s, 1 H, NHAr), 3.55 (s, 2 H, CH2CO), 3.38 (q, 2 H, J = 6.7 Hz,
,
Synthesis 2002, No. 18, 2687–2690 ISSN 0039-7881 © Thieme Stuttgart · New York

2690
M. B. García et al.
PAPER
2-Ethyl-1-(o-nitrophenyl)-1,4,5,6-tetrahydropyrimidine (3f)
J = 8.7 Hz), 6.68 (dt, 1 Harom, J1 = 8.6, J2 = 1.3 Hz), 5.49 (br s, 1 H,
NHAr), 3.52 (s, 2 H, CH2CO), 3.41 (q, 2 H, J = 6.9 Hz, CH2N), 3.28
(q, 2 H, J = 6.9 Hz, CH2N), 1.55–1.74 (m, 4 H).
MS: m/z = 361 (M.+).
Yield: 75%; oil.
1H NMR: = 7.93 (dd, 1 Harom, J1 = 8.0, J2 = 1.6 Hz), 7.63 (dt, 1
Harom, J1 = 7.7, J2 = 1.6 Hz), 7.45–7.49 (m, 1 Harom), 7.36 (d, 1 Harom,
J1 = 7.7 Hz), 3.46–3.50 (m, 4 H, CH2N), 2.02 (q, 2 H, J = 7.3 Hz,
CH2CH3), 1.89 (pent, 2 H, J = 6.1 Hz, CH2CH2CH2), 1.02 (t, 3 H,
J = 7.3 Hz, CH2CH3).
MS: m/z = 233 (M.+).
5-Aryl-2,3-dihydro-1H-pyrimido[1,2-a]quinoxaline 6-Oxides
1a–d; General Procedure
A mixture of the corresponding diamine 2a–d (0.5 g) and PPE8 (10
mL) was refluxed for 5 h. After cooling, the mixture was extracted
with H2O (5 10 mL). The resulting aqueous acidic solutions were
pooled, filtered, made alkaline (pH 12) with NaOH, and was ex-
tracted with CHCl3 (3 20 mL). The organic phases were com-
bined, washed with H2O, dried (Na2SO4) and filtered. The CHCl3
solution was left at r.t. until the disappearance of intermediate 3 as
monitored by TLC (silica gel, CHCl3–MeOH, 9:1) (ca. 24 h). The
solvent was removed in vacuo and the crude product was purified
by column chromatography (silica gel, CHCl3–MeOH, 10:0 9:1)
(Table. 1).
Anal. Calcd for C12H15N3O2: C, 61.79; H, 6.48; N, 18.01. Found: C,
61.84; H, 6.52; N, 17.94.
6-(p-Chlorophenyl-1,2,3,4-tetrahydro-1,3-diazepino[1,2-a]-
quinoxaline 7-Oxide (1g)
The same procedure as for compounds 1a–d was used. Reaction
time with PPE was 30 h. The intermediate 3g disappeared in ca. 36
h.Yield, physical and spectral data of compound 1g are given in
Table 1.
5-Alkyl-2,3-dihydro-1H-pyrimido[1,2-a]quinoxaline 6-Oxides
1e,f; General Procedure
Acknowledgments
A mixture of the corresponding diamine 2e,f (0.5 g) and a CH2Cl2
solution of PPSE9 (10 mL) was refluxed for 5 h. After cooling, the
mixture was extracted with H2O (5 10 mL). The resulting acid so-
lutions were pooled, filtered, made alkaline (pH 9) with NaHCO3,
and extracted with CHCl3 (3 20 mL). The organic phases were
combined, washed with H2O, dried (Na2SO4) and filtered. After re-
moval of the solvent in vacuo, the residual crude products were pu-
rified by column chromatography (silica gel, CH2Cl2–
isopropylamine, 100:1 20:1), yielding compounds 3e,f (vide in-
fra). A CHCl3 solution of the corresponding amidine was left at r.t.
until disappearance of the starting material as monitored by TLC
(silica gel, CHCl3–MeOH, 9:1) (ca. 4 and 7 days for compounds 1e
and 1f, respectively). The solvent was then removed in vacuo and
the crude product was purified by column chromatography (silica
gel, CHCl3–MeOH, 10:0 9:1) (Table 1).
This work was supported by the Universidad de Buenos Aires and
by CONICET (Consejo Nacional de Investigaciones Científicas y
Técnicas). A Doctoral Fellowship from Fundación Antorchas for
M. B. García is also acknowledged.
References
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1-(o-Nitrophenyl)-2-(2-phenylethyl)-1,4,5,6-tetrahydropyrimi-
dine (3e)
Yield: 73%; mp 68–70 °C (CH2Cl2–cyclohexane).
1H NMR: = 7.90 (dd, 1 Harom, J1 = 8.2, J2 = 1.5 Hz), 7.57 (t, 1
Harom, J = 7.7 Hz), 7.42 (t, 1 Harom, J = 7.7 Hz), 7.12–7.21 (m, 4
Harom), 6.96–6.99 (m, 2 Harom), 3.63 (t, 2 H, J = 6.6 Hz, CH2N), 3.53
(t, 2 H, J = 5.5 Hz, CH2N), 2.71–2.80 (m, 4 H, CH2CH2C6H5), 1.99–
2.07 (m, 2 H, CH2CH2CH2).
MS: m/z = 309 (M+.).
(8) Pollmann, W.; Schramm, G. Biochim. Biophys. Acta 1964,
80, 1.
(9) Yokohama, M.; Yoshida, S.; Imamoto, T. Synthesis 1982,
591.
Anal. Calcd for C18H19N3O2: C, 69.88; H, 6.19; N, 13.58. Found: C,
69.81; H, 6.24; N, 13.50.
Synthesis 2002, No. 18, 2687–2690 ISSN 0039-7881 © Thieme Stuttgart · New York