A new approach to the synthesis of Biginelli compounds

Article abstract of DOI:10.1070/MC2005v015n02ABEH002022

A new synthesis of 4-aryl-2-oxo-l,2,3,4-tetrahydropyrimidine-5-carboxylic acid esters is based on the reactions of α-tosyl-substituted phenyl carbamates with the enolates of β-oxoesters followed by treatment with ammonia and dehydration of the resulting 4

Full text of DOI:10.1070/MC2005v015n02ABEH002022

, 2005, 15(2), 70–72
A new approach to the synthesis of Biginelli compounds
Anatoly D. Shutalev* and Nikolay N. Kurochkin
Department of Organic Chemistry, M. V. Lomonosov Moscow State Academy of Fine Chemical Technology, 119571 Moscow,
Russian Federation. Fax: +7 095 434 8711; e-mail: shutalev@orc.ru
DOI: 10.1070/MC2005v015n02ABEH002022
A new synthesis of 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid esters is based on the reactions of α-tosyl-substi-
tuted phenyl carbamates with the enolates of β-oxoesters followed by treatment with ammonia and dehydration of the resulting
4-hydroxyhexahydropyrimidin-2-ones.
The synthesis of Biginelli compounds, namely, the esters of
2-oxo- and 2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic
acids 1, is of considerable interest1,2 because of diverse bio-
logical properties of these compounds. For example, they are
active antihypertensive agents,3,4 kinesin Eg5 inhibitors,5 α1a
adrenoceptor-selective antagonists,6 etc.
about 25 °C quite slowly (13–20 days). This may be explained
by the low solubility of reagents and intermediate products in
an aqueous medium. However, compounds 5a–c were obtained
in very high yields (91–96%). The reaction time decreased with
temperature. At 70 °C, the reaction was complete in 10 h to
provide 5a–c in 91–94% yields.†
We found that carbamates 5a–c readily reacted with the sodium
enolates of β-oxoesters (acetonitrile, room temperature, 4–6 h)
generated by the treatment of ethyl acetoacetate 6a or ethyl
benzoylacetate 6b with sodium hydride in dry acetonitrile. As a
result of this reaction, the products of nucleophilic substitution
of the tosyl group in 5a–c, namely, corresponding N-substituted
phenyl carbamates 7a–f, were produced in 74–93% yields
(Scheme 3).‡
The phenoxy group in 7a–f was replaced by the amino group
upon the treatment of 7a–f with an excess of ammonia in
acetonitrile at room temperature. The reaction time depended
on the molar ratio of 7a–f to ammonia, and it was found to be
approximately 24 h at a ratio of 1:13 or 5–6 h at a ratio of 1:60.
The products of this reaction, ethyl 4-hydroxy-2-oxohexahydro-
pyrimidine-5-carboxylates 9a–f, seem to be formed as a result
of the heterocyclisation of intermediate oxoalkylureas 8a–f
The one-step three-component Biginelli condensation (A)7,8
and the multi-stage Atwal procedure (B)9–11 are well-known syn-
thetic methods providing access to pyrimidines 1 (Scheme 1).
A limitation of these methods is their low adaptability in obtaining
some types of 1, especially those containing hydrogen atoms or
an alkyl group at the 4-position (R = H, alkyl).
COOR2
R1
COOR2
R1
COOR2
R1
R
R
R
HC
O
O
O
HN
NH
A
B
HN
NH2
H2N
NH2
X
X
X
R3
1
X = O, S
Scheme 1
†
Synthesis of 5a: A 50 ml Erlenmeyer flask with a magnetic stirring bar
was charged with water (14.5 ml) and benzaldehyde (1.290 g, 12.16 mmol).
Then, p-toluenesulfinic acid18 (1.938 g, 12.41 mmol) was added with
stirring, and the resulting mixture was stirred at room temperature for
10 min. Phenyl carbamate 4 (1.667 g, 12.16 mmol) was added to the
suspension. The flask was closed with a glass stopper, and the reaction
mixture was heated at 70 °C (water bath) with stirring for 9 h 52 min. At
the beginning of heating the solid turned into an oil-like substance,
which became a mass of fine crystals after 15–20 min. After the reaction
was complete, the obtained creamy mixture was cooled to 0 °C, the solid
was filtered off, washed with ice water and light petroleum, and dried to
give 4.205 g (90.7%) of 5a.¶
Recently,12,13 we developed a new general synthesis of com-
pounds 1 based on the reaction of α-tosyl-substituted ureas
or thioureas with enolates of β-oxoesters. Oxoalkyl(thio)ureas,
which are intermediates of this reaction, undergo spontaneous
cyclization into the corresponding 4-hydroxyhexahydropyrimidin-
2-ones/thiones. The latter are dehydrated to give Biginelli com-
pounds. We assumed that the oxoalkyl(thio)ureas can also be
generated in the reaction of suitable (thio)carbamates containing
an easily leaving group (for example, the phenoxy group) with
ammonia or primary amines. Here, we describe preliminary
results of the synthesis of 1.
Similarly, compounds 5b,c were prepared by the reaction of phenyl
carbamate 4 with p-toluenesulfinic acid and 4-methylbenzaldehyde 3b
or 4-methoxybenzaldehyde 3c in 92.6 and 94.1% yields, respectively.
According to 1H NMR data, carbamates 5a–c contained only a small
amount of impurities; therefore, they were used in the synthesis of 7a–f
without further purification. Analytically pure samples of 5a–c were
obtained after recrystallisation from hexane–ethyl acetate (1:1, v/v).
The key starting compounds, α-tosyl-substituted phenyl car-
bamates 5a–c, were prepared by the reactions of p-toluenesulfinic
acid 2 with aromatic aldehydes 3a–c and phenyl carbamate 4 in
water (Scheme 2). We found that this reaction proceeded at
HO
O
O
H
‡
Synthesis of 7a: A solution of ethyl acetoacetate 6a (0.907 g, 6.97 mmol)
S
C
in dry acetonitrile (7 ml) was added dropwise to a stirred suspension of
NaH (0.167 g, 6.96 mmol) in dry acetonitrile (11 ml) over a period
of 2 min at room temperature. After hydrogen evolution finished, to the
resulting solution of sodium enolate of ethyl acetoacetate was added
carbamate 5a (2.391 g, 6.27 mmol) and additional 4 ml of dry aceto-
nitrile. The reaction mixture with a white precipitate was stirred for 6 h
at room temperature. Then, the solvent was removed under reduced
pressure, and a saturated aqueous solution of NaHCO3 (6 ml) and light
petroleum (5 ml) were added to a white residue. The mixture with the
white precipitate was allowed to stand for 2 h at room temperature and
then cooled to 0 °C; the precipitate was filtered off, washed with ice
water and light petroleum and dried to give 1.840 g (82.6%) of 7a as a
mixture of two diastereomers.¶
H2N
OPh
O
Me
Me
2
3a–c
4
O
O
H
S
N
OPh
O
Me
Similarly, compounds 7b–f were prepared by the reactions of 5a with
1
6b and 5b,c with 6a,b in 74–93% yields. According to H NMR data,
a R = H
carbamates 7a–f contained only a small amount of impurities; there-
fore, they were used in the synthesis of 1a–f and 9a–f without further
purification. Analytically pure samples of 7a–f were obtained after
recrystallisation from hexane–ethyl acetate (1:1, v/v).
R
b R = Me
c R = OMe
5a–c
Scheme 2
70 Mendeleev Commun. 2005

, 2005, 15(2), 70–72
References
R1
O
O
1 C. O. Kappe, Tetrahedron, 1993, 49, 6937.
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Parham, P. G. Sleph and S. Moreland, J. Cardiovasc. Pharmacol., 1995,
26, 289.
H
O
O
EtO
N
OPh
i, NaH, MeCN
ii, 5a–c
R1
O
OEt
5 S. J. Haggarty, T. U. Mayer, D. T. Miyamoto, R. Fathi, R. W. King,
T. J. Mitchison and S. L. Schreiber, Chem. Biol., 2000, 7, 275.
6 D. Nagarathnam, S. W. Miao, B. Lagu, G. Chiu, J. Fang, T. G. M. Dhar,
J. Zhang, S. Tyagarajan, M. R. Marzabadi, F. Q. Zhang, W. C. Wong,
W. Y. Sun, D. Tian, J. M. Wetzel, C. Forray, R. S. L. Chang, T. P.
6a R1 = Me
R
6b R1 = Ph
7a–f
NH3
R1
O
O
¶
The 1H and 13C NMR spectra were recorded on a Bruker DPX 300
spectrometer at 300.13 (1H) and 75.476 (13C) MHz as solutions in
[2H6]DMSO. The IR spectra were obtained on a Bruker Equinox 55/S
Fourier spectrometer in KBr pellets (for 1a–f, 5a) or Nujol (for 7a).
Ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-car-
boxylate 1a: mp 204–204.5 °C (from ethanol) (lit.,8 mp 202.4 °C; lit.,14
mp 204–205 °C). 1H NMR, d: 9.20 [s, 1H, N(1)H], 7.74 [br. s, 1H,
N(3)H], 7.19–7.37 (m, 5H, Ph), 5.15 (d, 1H, 4-H, J4-H,N-H 3.1 Hz), 3.98
(q, 2H, OCH2Me, J 7.1 Hz), 2.25 (s, 3H, 6-Me), 1.09 (t, 3H, OCH2Me,
J 7.1 Hz). 13C NMR, d: 165.33 (C=O in COOEt), 152.13 [C(2)], 148.35
[C(6)], 144.86 [C(1) in Ph], 128.38 [C(3) and C(5) in Ph], 127.25 [C(4)
in Ph], 126.24 [C(2) and C(6) in Ph], 99.25 [C(5)], 59.17 (OCH2Me),
53.96 [C(4)], 17.77 (6-Me), 14.06 (OCH2Me). IR, n/cm–1: 3365 (m),
3246 (s), 3116 (s, νN–H), 1726 (vs, νC=O in COOEt), 1702 (vs, amide-I),
1648 (vs, νC=C), 1601 (w, νCC in Ph), 1224 (vs), 1092 (vs, νC–O), 760 (s),
H
N
R
EtO
NH2
COOEt
OH
O
R1
HN
NH
O
R
9a–f
TsOH
8a–f
R
COOEt
R1
a R = H, R1 = Me
b R = H, R1 = Ph
c R = R1 = Me
700 (s, δC –H). Found (%): C, 64.67; H, 6.33; N, 10.73. Calc. for
C14H16N2O3 (%): C, 64.60; H, 6.20; N, 10.76.
arom
HN
NH
Ethyl 2-oxo-4,6-diphenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate
1b: mp 157–159 °C (from ethanol) (lit.,15 mp 157–159 °C). 1H NMR,
d: 9.32 [br. d, 1H, N(1)H, JNH,NH 2.0 Hz], 7.87 [br. dd, 1H, N(3)H, JNH,NH
2.0 Hz, J4-H,NH 3.5 Hz], 7.25–7.46 (m, 10H, 4-Ph and 6-Ph), 5.24 (d, 1H,
4-H, J4–H,NH 3.5 Hz), 3.71 (q, 2H, OCH2Me, J 7.1 Hz), 0.72 (t, 3H,
OCH2Me, J 7.1 Hz). 13C NMR, d: 165.13 (C=O in COOEt), 152.14
[C(2)], 149.00 [C(6)], 144.42 [C(1) in 4-Ph], 135.08 [C(1) in 6-Ph],
128.89 [C(4) in 6-Ph], 128.55 [C(3) and C(5) in 4-Ph], 128.36 [C(2) and
C(6) in 6-Ph], 127.74 [C(3) and C(5) in 6-Ph], 127.44 [C(4) in 4-Ph],
126.32 [C(2) and C(6) in 4-Ph], 100.39 [C(5)], 59.09 (OCH2Me), 54.15
[C(4)], 13.38 (OCH2Me). IR, n/cm–1: 3361 (s), 3199 (m), 3080 (m),
3063 (m, νN–H), 3029 (m, νC -H), 1698 (vs, νC=O in COOEt), 1664 (vs,
amide-I), 1640 (m, νC=C), 1a5ro9m9 (m), 1494 (m, νCC in Ph), 1252 (vs),
d R = Me, R1 = Ph
e R = OMe, R1 = Me
f R = OMe, R1 = Ph
O
1a–f
Scheme 3
(Scheme 3). Hydroxypyrimidines 9a–f were dehydrated without
isolation by refluxing in ethanol in the presence of p-toluene-
sulfonic acid (60 mol%) to give target pyrimidines 1a–f§ in
71–80% yields based on 7a–f.
The structures of all the obtained compounds were determined
by IR, 1H and 13C NMR spectroscopy and elemental analysis.¶
In summary, we developed a new general three-stage method
for the synthesis of Biginelli compounds. This method is char-
acterised by high overall yields (up to 70% based on phenyl
carbamate 4) of the target products. In comparison with the
known synthetic procedures (see Scheme 1), our approach is
more flexible and potentially allows a wide variety of substi-
tuents at N(1), C(4), C(5) and C(6) atoms of the pyrimidine ring.
In particular, 4-alkyl-substituted and 4-unsubstituted Biginelli
compounds, as well as 1,2,3,4-tetrahydropyrimidin-2-ones bearing
other functional groups at the C(5) atom, can be readily obtained
according to this method.
1084 (vs, νC–O), 756 (s), 692 (s, δC –H). Found (%): C, 70.66; H, 5.67;
N, 8.68. Calc. for C19H18N2O3 (%): C, 70.79; H, 5.63; N, 8.69.
arom
Ethyl 6-methyl-4-(4-methylphenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-
5-carboxylate 1c: mp 214–214.5 °C (from ethanol) (lit.,16 mp 215–216 °C;
lit.,17 mp 170–171 °C). 1H NMR, d: 9.16 [s, 1H, N(1)H], 7.69 [br. s, 1H,
N(3)H], 7.12 (s, 4H, C6H4), 5.11 (d, 1H, 4-H, J4-H,NH 3.2 Hz), 3.98 (q,
2H, OCH2Me, J 7.1 Hz), 2.26 and 2.24 (2s, 2×3H, 6-Me, 4-MeC6H4),
1.10 (t, 3H, OCH2Me, J 7.1 Hz). 13C NMR, d: 165.34 (C=O in COOEt),
152.16 [C(2)], 148.13 [C(6)], 141.94 [C(1) in 4-MeC6H4], 136.34 [C(4)
in 4-MeC6H4], 128.87 [C(3) and C(5) in 4-MeC6H4], 126.13 [C(2) and
C(6) in 4-MeC6H4], 99.40 [C(5)], 59.13 (OCH2Me), 53.61 [C(4)], 20.62
(4-MeC6H4), 17.74 (6-Me), 14.08 (OCH2Me). IR, n/cm–1: 3246 (s), 3117
(s, νN–H), ~1721 (sh, νC=O in COOEt), 1705 (vs, amide-I), 1650 (vs,
ν
C=C), 1513 (m, νCC in C6H4), 1225 (vs), 1091 (vs, νC–O). Found (%): C,
§
Synthesis of 1b: A 25% aqueous ammonia solution (3.70 ml, 3.35 g,
65.60; H, 6.81; N, 10.11. Calc. for C15H18N2O3 (%): C, 65.68; H, 6.61;
N, 10.21.
49.2 mmol) was added to a suspension of 7b (0.343 g, 0.82 mmol) in
acetonitrile (7.4 ml), and the mixture was stirred at room temperature for
9 h 40 min. The solution was evaporated to dryness in a vacuum; the
residue was dried in a vacuum dessicator over P2O5. Then, TsOH·H2O
(0.094 g, 0.49 mmol) and ethanol (3.5 ml) were added, and the resulting
solution was refluxed for 1 h 40 min. The solvent was removed under
reduced pressure; water (2 ml) and an aqueous 1 M NaOH solution
(2.5 ml) were added to the oil-like residue. The residue was rubbed up
with a spatula to complete solidification. The mixture was cooled to
0 °C, the precipitate was filtered off, washed with ice water and light
petroleum and dried to give 1b (0.213 g, 80.4%).
Ethyl 4-(4-methylphenyl)-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrimidine-
5-carboxylate 1d: mp 164.5–167 °C (from ethanol). 1H NMR, d: 9.22 [s,
1H, N(1)H], 7.77 [br. s, 1H, N(3)H], 7.24–7.44 (m, 5H, 6-Ph), 7.27 [m,
2H, AA' part of AA'XX' spin system, C(2)H and C(6)H in 4-MeC6H4,
Jortho 8.1 Hz], 7.18 [m, 2H, XX' part of AA'XX' spin system, C(3)H and
C(5)H in 4-MeC6H4, Jortho 8.1 Hz], 5.20 (d, 1H, 4-H, J4-H,NH 3.5 Hz),
3.71 (q, 2H, OCH2Me, J 7.1 Hz), 2.29 (s, 3H, 4-MeC6H4), 0.72 (t, 3H,
OCH2Me, J 7.1 Hz). 13C NMR, d: 165.12 (C=O in COOEt), 152.15
[C(2)], 148.74 [C(6)], 141.52 [C(1) in 4-MeC6H4], 136.54 [C(4) in
4-MeC6H4], 135.11 [C(1) in Ph], 129.03 [C(3) and C(5) in 4-MeC6H4],
128.83 [C(4) in Ph], 128.33 [C(2) and C(6) in Ph], 127.71 [C(3) and
C(5) in Ph], 126.20 [C(2) and C(6) in 4-MeC6H4], 100.58 [C(5)], 59.04
(OCH2Me), 53.84 [C(4)], 20.67 (4-MeC6H4), 13.39 (OCH2Me). IR,
Similarly, compounds 1d,f were prepared using 7d,f as starting materials
in 73.6 and 70.8% yields, respectively.
Synthesis of 1a,c,e: Syntheses were carried out using 7a,c,e as starting
materials analogously to the synthesis of 1b,d,f with the following excep-
tions: after the dehydration stage was accomplished, the corresponding
reaction mixture was cooled to –10 °C, the resulting precipitate was
filtered off, slightly washed with cold (0 °C) ethanol and dried to give
1a,c,e in 79.6, 71.0 and 72.4% yields, respectively.
n/cm–1: 3305 (s), 3223 (s), 3114 (s, νN–H), 3055 (m), 3029 (m, νC –H),
arom
1705 (vs, νC=O in COOEt), 1667 (vs, amide-I), 1640 (m, νC=C), 1598 (m),
1512 (m, νCC in Ph and C6H4), 1246 (vs), 1097 (s, νC–O), 840 (m, δC
arom–H
in C6H4), 767 (m), 701 (m, δC –H in Ph). Found (%): C, 71.19; H, 5.94;
N, 8.27. Calc. for C20H20N2O3aro(m%): C, 71.41; H, 5.99; N, 8.33.
Mendeleev Commun. 2005 71

, 2005, 15(2), 70–72
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Ethyl 4-(4-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-
5-carboxylate 1e: mp 205–206 °C (from ethanol) (lit.,14 mp 204–205 °C;
lit.,16 mp 202–204 °C). 1H NMR, d: 9.15 [br. d, 1H, N(1)H, JNH,NH
2.1 Hz], 7.67 [br. dd, 1H, N(3)H, J4-H,NH 3.2 Hz, JNH,NH 2.1 Hz], 7.14
[m, 2H, AA' part of AA'XX' spin system, C(2)H and C(6)H in
4-MeOC6H4, Jortho 8.7 Hz], 6.87 [m, 2H, XX' part of AA'XX' spin
system, C(3)H and C(5)H in 4-MeOC6H4, Jortho 8.7 Hz], 5.09 (d, 1H,
4-H, J4-H,NH 3.2 Hz), 3.98 (q, 2H, OCH2Me, J 7.1 Hz), 3.71 (s, 3H,
OMe), 2.24 (s, 3H, 6-Me), 1.10 (t, 3H, OCH2Me, J 7.1 Hz). 13C NMR,
d: 165.37 (C=O in COOEt), 158.43 [C(4) in 4-MeOC6H4], 152.16
[C(2)], 148.01 [C(6)], 137.05 [C(1) in 4-MeOC6H4], 127.39 [C(2) and
C(6) in 4-MeOC6H4], 113.69 [C(3) and C(5) in 4-MeOC6H4], 99.55
[C(5)], 59.14 (OCH2Me), 55.04 (OMe), 53.33 [C(4)], 17.75 (6-Me),
14.10 (OCH2Me). IR, n/cm–1: 3244 (s), 3113 (s, νN–H), 1725 (vs, νC=O in
COOEt), 1706 (vs, amide-I), 1651 (vs, νC=C), 1613 (m), 1584 (m), 1513
Received: 1st September 2004; Com. 04/2347
(m, νCC in C6H4), 1224 (vs), 1091 (vs, νC–O), 841 (m, δC –H). Found
arom
Phenyl [1-aryl-2-(ethoxycarbonyl)-3-oxobutyl]carbamates 7a–f gave
expected spectral and analytical data. As an example for 7a (mixture of
two diastereomers, 57:43): 1H NMR spectrum of the major isomer, d:
8.47 (d, 1H, NH, JNH,CH 8.9 Hz), 7.24–7.42 [m, 7H, Ph and C(3)H,
C(5)H in OPh, the signals overlapped with signals of corresponding
protons of the minor isomer], 7.15–7.22 [m, 1H, C(4)H in OPh, the
signals overlapped with signals of corresponding protons of the minor
isomer], 6.99–7.04 (m, 2H, C(2)H, C(6)H in OPh, the signals over-
lapped with signals of corresponding protons of the minor isomer), 5.18
(dd, 1H, CH–Ph, JNH,CH 8.9 Hz, JCH,CH 11.3 Hz), 4.19 (d, 1H, CH–Ac,
JCH,CH 11.3 Hz), 4.21 (m, 1H, A part of ABX3 spin system, OCHAHBMe,
JAB 10.8 Hz, JAX 7.1 Hz), 4.16 (m, 1H, B part of ABX3 spin system,
OCHAHBMe, JAB 10.8 Hz, JBX 7.1 Hz), 2.32 (s, 3H, Ac), 0.89 (t, 3H,
OCH2Me, J 7.1 Hz). 1H NMR spectrum of minor isomer, d: 8.44 (d, 1H,
NH, JNH,CH 9.5 Hz), 7.24–7.42 [m, 7H, Ph and C(3)H, C(5)H in OPh,
the signals overlapped with signals of corresponding protons of the
major isomer], 7.15–7.22 [m, 1H, C(4)H in OPh, the signals overlapped
with signals of corresponding protons of the major isomer], 6.99–7.04
[m, 2H, C(2)H, C(6)H in OPh, the signals overlapped with signals of
corresponding protons of the major isomer], 5.24 (dd, 1H, CH–Ph,
JNH,CH 9.5 Hz, JCH,CH 10.8 Hz), 4.33 (d, 1H, CH–Ac, JCH,CH 10.8 Hz),
3.87 (q, 2H, OCH2Me, J 7.1 Hz), 2.01 (s, 3H, Ac), 1.21 (t, 3H,
OCH2Me, J 7.1 Hz). 13C NMR spectrum of major isomer, d: 200.38
(C=O in Ac), 166.05 (COOEt), 153.42 (NH–C=O), 150.78 [C(1) in
OPh], 139.80 [C(1) in Ph], 129.32 [C(3) and C(5) in Ph], 128.39 [C(3)
and C(5) in OPh], 127.81 [C(4) in Ph], 127.36 [C(2) and C(6) in Ph],
125.08 [C(4) in OPh], 121.53 [C(2) and C(6) in OPh], 64.38 (CH–Ac),
61.13 (OCH2Me), 54.12 (CH–N), 29.50 (COMe), 13.53 (OCH2Me).
13C NMR spectrum of the minor isomer, d: 200.60 (C=O in Ac), 166.79
(COOEt), 153.42 (NH–C=O), 150.85 [C(1) in OPh], 139.77 [C(1) in
Ph], 129.32 [C(3) and C(5) in Ph], 128.50 [C(3) and C(5) in OPh],
127.76 [C(4) in Ph], 127.39 [C(2) and C(6) in Ph], 125.08 [C(4) in OPh],
121.53 [C(2) and C(6) in OPh], 64.09 (CH–Ac), 61.31 (OCH2Me), 53.86
(CH–N), 30.06 (COMe), 13.94 (OCH2Me). IR, n/cm–1: 3380 (s, νN–H),
(%): C, 62.25; H, 6.30; N, 9.68. Calc. for C15H18N2O4 (%): C, 62.06; H,
6.25; N, 9.65.
Ethyl 4-(4-methoxyphenyl)-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrimidine-
5-carboxylate 1f: mp 162.5–163.5 °C (from ethanol). H NMR, d: 9.26
1
[s, 1H, N(1)H], 7.79 [unsolved br. d, 1H, N(3)H], 7.26–7.45 [m, 7H,
6-Ph and C(2)H, C(6)H in 4-MeOC6H4], 6.94 [m, 2H, XX' part of
AA'XX' spin system, C(3)H and C(5)H in 4-MeOC6H4, Jortho 8.7 Hz],
5.18 (d, 1H, 4-H, J4-H,NH 3.4 Hz), 3.74 (s, 3H, OMe), 3.71 (q, 2H,
OCH2Me, J 7.1 Hz), 0.72 (t, 3H, OCH2Me, J 7.1 Hz). 13C NMR, d:
165.12 (C=O in COOEt), 158.56 [C(4) in 4-MeOC6H4], 152.12 [C(2)],
148.62 [C(6)], 136.57 [C(1) in 4-MeOC6H4], 135.14 [C(1) in Ph],
128.81 [C(4) in Ph], 128.33 [C(2) and C(6) in Ph], 127.71 [C(3) and
C(5) in Ph], 127.47 [C(2) and C(6) in 4-MeOC6H4], 113.84 [C(3) and
C(5) in 4-MeOC6H4], 100.70 [C(5)], 59.03 (OCH2Me), 55.07 (OMe),
53.54 [C(4)], 13.39 (OCH2Me). IR, n/cm–1: 3316 (s), 3202 (s), 3085 (s,
ν
N–H), 3032 (w), 3012 (w, νC –H), 1692 (vs, νC=O in COOEt), 1677 (vs,
arom
amide-I), 1634 (m, νC=C), 1608 (m), 1587 (w), 1510 (m, νCC in Ph and
C6H4), 1236 (vs), 1086 (s, νC–O), 836 (m, δC –H in C6H4), 769 (m), 696
arom
(m, δC
in Ph). Found (%):C, 68.15; H, 5.69; N, 7.87. Calc. for
C20H20N2O4 (%): C, 68.17; H, 5.72; N, 7.95.
arom–H
Phenyl [(aryl)(tosyl)methyl]carbamates 5a–c gave expected spectral
and analytical data. As an example for 5a: 1H NMR, d: 9.61 (d, 1H, NH,
JNH,CH 10.8 Hz), 7.81 [m, 2H, AA' part of AA'XX' spin system, C(2)H
and C(6)H in 4-MeC6H4, Jortho 8.2 Hz], 7.66–7.74 (m, 2H, Ph–C),
7.50 [m, 2H, XX' part of AA'XX' spin system, C(3)H and C(5)H in
4-MeC6H4, Jortho 8.2 Hz], 7.41–7.48 (m, 3H, Ph–C), 7.34 [m, 2H, C(3)H
and C(5)H in OPh], 7.19 [m, 1H, C(4)H in OPh], 6.79 [m, 2H, C(2)H
and C(6)H in OPh], 6.06 (d, 1H, CH–N, JNH,CH 10.8 Hz), 2.45 (s, 3H,
Me). 13C NMR, d: 153.65 (C=O), 150.38 [C(1) in OPh], 144.90 [C(4) in
4-MeC6H4], 133.65 [C(1) in 4-MeC6H4], 129.84 [C(1) in Ph], 129.75,
129.69, 129.40, 129.33 [C(2), C(6) and C(3), C(5) in 4-MeC6H4 and Ph],
129.49 [C(4) in Ph], 128.21 [C(3) and C(5) in OPh], 125.46 [C(4) in
OPh], 121.43 [C(2) and C(6) in OPh], 74.73 (CH–N), 21.12 (Me). IR,
n/cm–1: 3398 (m), 3355 (m), 3299 (m, νN–H), 3063 (w), 3036 (w, ν C –H),
arom
3058 (w), 3044 (w), 3031 (w, νC –H), 1719 (vs, νC=O in COOEt), 1705
1722 (vs, νC=O), 1593 (m), 1510 (m, νCC in C6H4, Ph and OPh), 1318 (s,
arom
(vs, νC=O in Ac and NH–C=O), 1491 (s, νCC in Ph and OPh), 1222 (s),
νas SO2), 1146 (vs, νs SO2), 815 (s, δ
arom
in C6H4), 757 (m), 702 (s,
δC –H in Ph and OPh). Found (%): C, 66.05; H, 5.09; N, 3.60. Calc. for
Carom–H
1215 (s), 1041 (m, νC–O), 762 (m), 705 (s, δ
–H). Found (%): C, 67.55;
H, 5.91; N, 3.87. Calc. for C20H21NO5 (%): C, 67.59; H, 5.96; N, 3.94.
Carom
C H19NO4S (%): C, 66.12; H, 5.02; N, 3.67.
21
72 Mendeleev Commun. 2005