An improved synthesis of Biginelli-type compounds via phase-transfer catalysis

Article abstract of DOI:10.1016/j.tetlet.2009.03.177

3,4-Dihydropyrimidin-2(1H)-one, 3,4-dihydropyrimidin-2(1H)-thione, and 3,4-dihydropyrimidin-2(1H)-imine derivatives were synthesized by modified Biginelli cyclocondensation reaction in a time-efficient manner with near quantitative yields starting from ap

Full text of DOI:10.1016/j.tetlet.2009.03.177

Tetrahedron Letters 50 (2009) 2889–2892
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An improved synthesis of Biginelli-type compounds via phase-transfer catalysis
b
a
a
Bahar Ahmed a, , Riaz A. Khan , Habibullah , Manoj Keshari
*
a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi 110 62, India
b Department of Industrial Chemistry, Integral University, Lucknow 226 026, India
a r t i c l e i n f o
a b s t r a c t
Article history:
3,4-Dihydropyrimidin-2(1H)-one, 3,4-dihydropyrimidin-2(1H)-thione, and 3,4-dihydropyrimidin-2(1H)-
imine derivatives were synthesized by modified Biginelli cyclocondensation reaction in a time-efficient
manner with near quantitative yields starting from appropriately substituted aromatic aldehyde,
b-ketoester and either urea, thiourea or guanidine as constituent synthons using tetra-butyl ammonium
bromide (TBAB) as catalyst for the first time.
Received 20 January 2009
Revised 20 March 2009
Accepted 26 March 2009
Available online 28 March 2009
Ó 2009 Published by Elsevier Ltd.
Keywords:
Biginelli reaction
Cyclocondensation
3,4-Dihydropyrimidin-2(1H)-one
3,4-Dihydropyrimidin-2(1H)-thione
3,4-Dihydropyrimidin-2(1H)-imine
Tetra-butyl ammonium bromide (TBAB)
Dihydropyrimidines are an important class of compounds
exhibiting broad spectra of pharmacological activities such as anti-
inflammatory, anti-microbial, a-1a-adrenergic receptor antagonist,
Cu(OTf)210, VCl311, Yb(OTf)3,12 and LaCl3ꢀ7H2O13, which significantly
improved the reaction output with reduced reaction times. The
polymer-supported, resin-bound isothiourea14, poly(4-vinylpyri-
dine-co-divinyl benzene–Cu-II) complex15, ceria/vinyl-pyrimidine
and antihypertensives.1,2 The development of dihydropyrimidine
templates as pharmacologically active compounds contributed
toward Biginelli cyclocondensation applications in drug industry.
The contemporary advances in marine natural products chemistry
with structure diversification in dihydropyrimidine nucleus also
found synthetic attention3–7 from Biginelli reaction. More recently,
advances in the involvement of newer catalytic systems involve-
ment in solid phase, parallel and other combinatorial synthetic
approaches contributed toward expansion of Biginelli cycloconden-
sation applications. The three-component cyclocondensation
reaction constituting aldehyde, b-ketoester, and urea in an acidic
medium3 was refluxed using ethanolic/methanolic HCl in the classi-
cal synthesis while other solvent-cum-acidic catalytic systems such
as THF–HCl and dioxane–HCl were also employed with H2SO4 as a
replaceable acidic source in later developments. The major draw-
backs associated with acid-catalyzed reactions were lower yields1
(from 26% to 60%), particularly for tri and tetra-substituted alde-
hydes of aromatic and aliphatic origins as well as extended reaction
times from 24 to 36 h. The increasing interest in this class of com-
pounds led to the development of other synthetic strategies with
alternate catalysts. The recent interests in Biginelli cyclocondensa-
tion for its tailor-made suitability in high throughput synthesis8
polymer nanocomposite16, N-butyl-N,N-dimethyl-
a-phenyl-ethyl
ammonium bromide,17 and various other catalysts have been suc-
cessfully used for syntheses of Biginelli products.
In search of an inexpensive and environmentally benign cata-
lyst, tetra-butyl ammonium bromide (TBAB) was tested as an alter-
native catalyst with various substrates. The cost, availability, and
compatibility across phases in biphasic organic-aqueous layer het-
erogeneous reaction systems, with water as solvent, TBAB was
found to be a better catalyst. The current work describes this
approach toward Biginelli reaction with higher versatility for the
introduction of new substitution patterns. We report, herein, the
use of tetra-butyl ammonium bromide as an environment friendly,
bio-compatible, inexpensive, neutral, and high yielding (90–96%)
as well as short time-path (40–120 min) catalyst in producing
new heterocyclic products in comparison to other known method-
ology. This observation is also of significant importance for labora-
tory and bulk scales preparation of Biginelli-type products in wet
and solid phase chemistry.
We have undertaken the synthesis of different derivatives of
3,4-dihydropyrimidin-2(1H)-one, 3,4-dihydropyrimidin-2(1H)-thi-
one, and 3,4-dihydropyrimidin-2(1H)-imines from a variety of sub-
strates from aromatic aldehydes, ethylacetoacetate 18 and either
urea/ thiourea or guanidine. The benzaldehyde derivatives with
substitutions in the aromatic ring with 4-methyl, n-halogens
(n = varying ring substitution positions), 2-hydroxy, n-methoxy,
have found Lewis acid catalysts, for example, Mn(OAc)3.2H2O9
,
* Corresponding author. Tel.: +91 011 2605 9688x5623.
E-mail address: drbahmed@rediffmail.com (B. Ahmed).
0040-4039/$ - see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2009.03.177

2890
B. Ahmed et al. / Tetrahedron Letters 50 (2009) 2889–2892
CHO
R
O
O
X
i
O
+
+
R
H3C
OCH2CH3
H2N
NH2
H5C2O
NH
X = O, S, NH
H3C
N
H
1-17
X
R= [H/4-CH3/n-Cl/4-F/2-OH/n-OCH3/n-OCH3x2/
n-OCH3x3/n-NO2/N-N(CH3)2]
X= O
R= H/n-NO2 /n-Cl/4-F
X= NH
R= H/4-CH3/n-OCH3x2/N-N(CH3)2
X= S
R= 2-OH/n-OCH3/n-Cl/n-OCH3/N-N(CH3)2
Scheme 1. General synthetic scheme of compounds 1–17. Reagents and conditions: (i) TBAB (1.5 M), aq KOH (10% w/v), 100 °C, 40–120 min.
Table 1
Molecular formulae, melting point, time-cycle, and yield comparison profiles of compounds 1–17
Compd
Substitution
Molecular formulae
Melting point (°C)
Time (min)
Yielda (%)
R
X
Found
Reported
1
2
3
4
5
6
7
8
H
O
O
O
O
O
O
S
S
S
S
S
S
NH
NH
NH
NH
NH
C14H16N2O3
C14H15N3O5
C14H15N3O5
C14H15N3O5
C14H15ClN2O3
C14H15FN2O3
C14H16N2O3S
C15H18N2O3S
C14H15ClN2O2S
C14H15ClN2O2S
C16H20N2O4S
C16H21N3O2S
C14H17N3O2
C15H19N3O2
C17H23N3O5
C16H21N3O4
C16H22N4O2
204–206
216–218
225–227
210–212
207–209
186–188
206–208
141–143
219–221
240–242
212–214
209–210
176–178
Oil
200–202
—
225–227
205–207
209–211
—
—
138–140
—
—
—
40
45
45
55
50
50
70
60
50
65
65
100
45
75
55
60
120
96b
94c
90b
90b
88b
88d
80
2-Nitro
3-Nitro
4-Nitro
4-Chloro
4-Fluro
2-Hydroxy
4-Methoxy
2-Chloro
3-Chloro
96b
90
9
10
11
12
13
14
15
16
17
96
3,4-Dimethoxy
4-N,N-Dimethyl amino
H
90
209–210
94e
92
—
—
—
—
—
4-Methyl
89
87
89
94
2,3,4-Trimethoxy
3,4-Dimethoxy
4-N,N-Dimethyl amino
125–127
101–103
163–165
a
Isolated yield.
Ref. 20.
Ref. 9.
Ref. 21.
Ref. 19.
b
c
d
e
varying nitro positions and N,N-dimethylamino groups were
reacted with urea, thiourea, and guanidine to furnish a series of
products 1–17 (Scheme 1, Table 1). The higher yields and shorter
reaction times validated the mechanistic approach suggested by
Kappe18, whereby the aldol adduct 24 formed from aromatic alde-
hyde derivative and urea variant is approached by the b-keto ester
in enolate form as the attacking species (Scheme 2).
The TBAB plays an important role as a catalyst in the synthesis
of dihydropyrimidine and other related derivatives and product
variants with O, S, and NH as the C-2 substitution in dihydropy-
rimidine nucleus. The TBAB participation in catalyzing the Bigi-
nelli reaction can be understood by proposed mechanism
(Scheme 2). The reaction of b-keto ester, that is, ethylacetoacetate
18 with KOH affords the adduct 19 (K+-enolate), which is further
transformed to entity 20 (Q+-enolate) by ion-exchange between
Q+ (quaternary ammonium ion) from Q+ Brꢁ and K+-enolate ion
19 in the aqueous media. The quaternary ammonium ion-based
entity 20 (Q+-enolate) loses the quaternary ammonium ions (Q+)
to produce 26 (b-keto ester enolate), an equivalent of base-sup-
ported-proton-abstraction-anionic entity. 26 reacts with 25, a
(QꢀꢀꢀC@N) electrophilic system generated by addition of Q+ to
imine adduct 24 (C@N) that itself is obtained from an aldol
adduct amine 23 by the reaction between starting aldehyde 8
and corresponding urea 22 in organic phase to produce the
open-chain uride product 27. The proposed mechanism between
aldehyde and urea/ thiourea/ guanidine generates an acyl imine
intermediate 24, which reacts with quaternary ammonium ion
generated from TBAB is supported by a similar mechanism of for-
mation of an intermediate 25 stabilized by participation of lone
pair of acyl imine N electrons (Nandurkar et al.22). The intermedi-
ate product 27 undergoes cyclization with removal of one mole of
water molecule leading to desired 3,4-dihydropyrimidin-2(1H)-
one as the final product 1.
The use of TBAB preserved the classical simplicity of Biginelli
one-pot synthesis and remarkably improved the yield profile and
time to complete the reaction (Table 1) in shorter span
(40–120 min) than the reported longer times (6–7 h to previous
24–36 h). In order to further improve the reaction time and prod-
uct yield profile, the effects of ratios of three synthon components
namely, b-keto ester, aromatic aldehyde and urea, thiourea or gua-
nidine with varying concentrations of TBAB as catalyst were test
run. The optimized best yields and time profiles were obtained
with a molar ratio of 1:1:1:0.15 of b-keto ester, aromatic aldehyde,
urea/ thiourea or guanidine and TBAB as catalyst, respectively.

B. Ahmed et al. / Tetrahedron Letters 50 (2009) 2889–2892
2891
Ar
Organic phase
OH
X
Ar
H
- H2O
Base
+
O
Ar
ArCHO
NH2
NH2
21
H2N
NH2
N
NH
23
EtO
NH
Ar
22
X
24
X
Me
N
H
1
X
+ Q+
Ar
H
-
- H2O
CHCOOEt
+
NH2
COCH3
26
N
CH3COCH
NH
Q+
-
Q
Q+CHCOOEt
27
X
25
X
COOEt
H2N
20
COCH3
Q+
-
Q+
(Q+ = Quaternary ammonium ion)
Aqueous phase
Q+
CHCOOEt
20
COCH3
- KBr
Q+Br
K+
CHCOOEt
+
CH3COCH2COOEt
KOH
COCH3
19
18
Scheme 2. Proposed mechanism of Biginelli reaction using TBAB.
7. Snider, B. B.; Chen, J.; Patil, A. D.; Freyer, A. J. Tetrahedron Lett. 1996, 37,
6977.
8. Sucholeiki, I. High-Throughput Synthesis: Principles and Practices; Marcel Decker:
New York, 2001.
R
O
9. Kumar, K. A.; Kasthuraiah, M.; Reddy, C. S.; Reddy, C. D. Tetrahedron Lett. 2001,
42, 7873.
9
10
4
1
10. Paraskar, A. S.; Dewkar, G. K.; Sudalai, A. Tetrahedron Lett. 2003, 44, 3305.
11. Sabitha, G.; Reddy, G. S. K. K.; Reddy, K. B.; Yadav, J. S. Tetrahedron Lett. 2003,
44, 6497.
12. Ma, Y.; Qian, C.; Wang, L.; Yang, M. J. Org. Chem. 2000, 65, 3864.
13. Lu, J.; Bai, Y.; Wang, Z.; Yang, B.; Ma, H. Tetrahedron Lett. 2000, 41, 9075.
14. Kappe, C. O. Bioorg. Med. Chem. Lett. 2001, 10, 49.
8
CH3CH2O
NH
3
2
7
H3C
N
X
H
Figure 1. General structures of compounds 1–17.
15. Yarapathi, R. V.; Kurva, S.; Tammishetti, S. Catal. Commun. 2004, 5, 511.
16. Sabitha, G.; Reddy, K. B.; Yadav, J. S.; Shailaja, D.; Sivudu, K. Tetrahedron Lett.
2005, 46, 8221.
17. Reddy, K. R.; Reddy, C. V.; Mahesh, M.; Raju, P. V. K. Tetrahedron Lett. 2003, 44,
8173.
18. Kappe, C. O. J. Org. Chem. 1997, 62, 7201.
19. Su, W.; Li, J.; Zheng, Z.; Shen, Y. Tetrahedron Lett. 2005, 46, 6037.
20. Shabaani, A.; Bazgir, A.; Teimouri, F. Tetrahedron Lett. 2003, 44, 857.
21. Dondoni, A.; Massi, A. Tetrahedron Lett. 2001, 42, 7975.
22. Nandurkar, N. S.; Bhanushali, M. J.; Bhor, M. D.; Bhanage, B. M. J. Mol. Catal. A:
Chem. 2007, 271, 14.
23. General method for synthesis of 5-ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihyd-
ropyrimidin-2(1H)-one, 3,4-dihydropyrimidin-2(1H)-thione, and 3,4-dihydropyrim-
idin-2(1H)-imine derivatives (1–17): Benzaldehyde or appropriately substituted
corresponding benzaldehyde derivatives (10 mmol), ethyl acetoacetate (10 mmol)
and either urea/thiourea or guanidines (10 mmol) were mixed together followed
by addition of 10% aqueous KOH (0.5 g in 5 mL water) and catalytic amount of
solid tetra-butyl ammonium bromide (0.483 g, 1.5 M) in a 100 mL round-
bottomed flask. The reaction mixture was heated with stirring at 100 °C for
appropriate time (Table 1). The progress of reaction was monitored by TLC and
after completion, the resultant mass was poured into crushed ice and solid
obtained was filtered through Buckner funnel, washed with ice-cold water,
twice with petroleum-ether, and air-dried over Buckner. The obtained oily
material was separated, neutralized with 5% aq HCl, water washed, dried over
anhydrous sodium sulphate, and concentrated under vacuo. The solid crude
products were recrystallized from ethanol.
The general synthetic scheme for 3,4-dihydropyrimidin-2(1H)-
one, 3,4-dihydropyrimidin-2(1H)-thione, 3,4-dihydropyrimidin-
2(1H)-imine, and their derivatives23 (1–17) has been depicted in
Scheme 1. The structures of all the new synthesized compounds
(Fig. 1) were established on the basis of their spectral (IR, 1H
NMR, mass spectra) and elemental analysis data.24 The melting
point, time required for preparation, and yield percentage of all
the products have been summarized in Table 1.
Acknowledgments
The authors are thankful to the Department of Pharmaceutical
Chemistry for providing necessary facilities. M.K. is thankful to
the University Grants Commission, New Delhi for GATE fellowship.
References and notes
24. Spectroanalytical data for new compounds: 5-Ethoxycarbonyl-6-methyl-4-(2-
hydroxyphenyl)-3,4-dihydropyrimidin-2(1H)-thione (7): IR (KBr): 3425, 3367,
1. Kappe, C. O. Tetrahedron 1993, 49, 6937.
2. Grover, G. I.; Dzwonczyk, S.; McMullen, D. M.; Normadin, D. E.; Parham, C. S.;
Sleph, P. G.; Moreland, S. J. Cardiovasc. Pharmacol. 1995, 26, 289.
3. Biginelli, P. Gazz. Chim. Ital. 1893, 23, 360.
1701, 1653, 1359, 1292 cmꢁ1
: d 1.04 (t,
1H NMR (300 MHz, MeOH-d4):
J = 7.2 Hz, 3H, CH3-10), 2.15 (s, 3H,CH3-7), 4.10 (d, 1H, Ar-OH), 4.22 (q, J = 7.2,
4.3 Hz , 2H, CH2O-9), 4.22 (s, 1H, CH-4), 7.21–6.81 (m, 4H, Ar-H), 8.46 (s, 1H,
NH-1), 9.57 (s, 1H, NH-3): Anal. Calcd for C14H16N2O3S: C, 57.52; H, 5.52; N,
9.58; S, 10.97%. Found: C, 57.56; H, 5.48; N, 9.56; S, 10.98.
4. Snider, B. B.; Shi, Z. J. Org. Chem. 1993, 38, 3828.
5. Patil, A. D.; Kumar, N. V.; Kokke, W. C.; Bean, M. F.; Freyer, A. J.; Brosses, C. D.;
Mai, S.; Truneh, A.; Faulkner, D. J.; Cart, B.; Breen, A. L.; Hertzberg, R. P.;
Johnson, R. K.; Wesley, J. W.; Potts, B. C. M. J. Org. Chem. 1995, 60, 1182.
6. Patil, A. D.; Freyer, A. J.; Taylor, P. B.; Carte, B.; Zuber, G.; Johnson, R. K. B.;
Faulkner, D. J.; Batzelladines, F. I. J. Org. Chem. 1997, 62, 1814.
5-Ethoxycarbonyl-6-methyl-4-(2-chlorophenyl)-3,4-dihydropyrimidin-2(1H)thi-
one (9): IR (KBr): 3319, 3270, 2969, 1695, 1645, 1358, 1311 cmꢁ1 1H NMR
:
(300 MHz, MeOH-d4): d 1.18 (t, J = 7.2 Hz, 3H, CH3-10), 2.0 (s, 3 H, CH3-7), 4.12
(q, J = 7.2, 4.3 Hz, 2H, CH2O-9), 5.11 (s, 1H, CH-4), 7.4–6.8 (m, 4H, Ar-H): 7.43

2892
B. Ahmed et al. / Tetrahedron Letters 50 (2009) 2889–2892
(s, 1H, NH-3), 9.26 (s, 1H, NH-1). Anal. Calcd for C14H15ClN2O2S. C, 54.10; H,
4.86; N, 9.01; S, 10.32. Found: C, 54.16; H, 4.82; N, 9.06; S, 10.28.
3 H, CH3-7), 5.47 (s, 1H, CH-4), 3.27 (s, 1H, =NH-2), 3.35 (q, J = 7.9, 4.4 Hz,
2H, CH2O-9), 7.30–7.23 (m, 5H, Ar-H), 7.41 (s, 1H, NH-3), 9.34 (s, 1H, NH-1);
Anal. Calcd for C15H19N3O2: C, 65.91; H, 7.01; N, 15.37. Found C, 65.95; H,
7.02; N, 15.34.
5-Ethoxycarbonyl-6-methyl-4-(3-chlorophenyl)-3,4-dihydropyrimidin-2(1H)-thi-
one (10): IR (KBr): 3420, 3284, 2975, 1710, 1641, 1353, 1285 cmꢁ1 1H NMR
:
(300 MHz, MeOH-d4): d 1.18 (t, J = 7.5 Hz, 3H, CH3-10), 2.23 (s, 3 H,CH3-7),
4.12 (q, J = 7.4, 4.4 Hz, 2H, CH2O-9), 4.12 (s, 1H, CH-4), 7.29–6.23 (m, 4H, Ar-H),
7.40 (s, 1H, NH-1), 9.32 (s, 1H, NH-3): Anal. Calcd for C14H15ClN2O2S: C, 54.10;
H, 4.86; N, 9.01; S, 10.32. Found: C, 54.08; H, 4.83; N, 9.05; S, 10.31.
5-Ethoxycarbonyl-6-methyl-4-(2,3,4-trimethoxyphenyl)-3,4-dihydropyrimidin-
2(1H)-imine (15): IR (KBr): 3257, 3104, 2976, 1641 cmꢁ1
:
1H NMR
(300 MHz, MeOH-d4): d 1.64 (s, 3H, Ar-CH3-40), 1.69 (t, J = 7.9 Hz, 3H, CH3-
10), 2.40 (s, 3 H, CH3-7), 5.47 (s, 1H, CH-4), 3.27 (s, 1H, =NH-2), 3.35 (q,
J = 7.9, 4.4 Hz, 2H, CH2O-9), 7.28 (s, 1H, NH-3), 7.30–7.23 (m, 5H, Ar-H), 8.92
(s, 1H, NH-1), Anal. Calcd for C17H23N3O5 : C, 58.44; H, 6.64; N, 12.03. Found
C, 58.47; H, 6.62; N, 12.05.
5-Ethoxycarbonyl-6-methyl-4-(3,4-dimethoxyphenyl)-3,4-dihydropyrimidin-2(1H)-
thione (11): IR (KBr): 3426, 3134, 2982, 1698, 1633, 1368, 1325, 1287 cmꢁ1 1H
:
NMR (300 MHz,MeOH-d4): d 1.20 (t, J = 7.9 Hz, 3H, CH3-10), 2.34 (s, 3 H, CH3-
7), 3.4 (s, 3H, Ar-OCH3-30), 3.88 (s, 3H, Ar-OCH3-40), 4.12 (q, J = 7.9, 4.6 Hz, 2H,
CH2O-9), 5.26 (s, 1H, CH-4), 6.9 (s, 1H, NH-3), 7.81–6.84 (m, 3H, Ar-H), 9.56 (s,
1H, NH-3); MS: m/z 336 (M+, C16H20N2O4S+, 62%), 291 (23), 277 (100), 263
(18), 232 (14), 204 (16). Anal. Calcd for C16H20N2O4S: C, 57.12; H, 5.99; N, 8.33;
S, 9.53. Found: C, 57.15; H, 5.97; N, 8.36; S, 9.52.
5-Ethoxycarbonyl-6-methyl-4-(3,4-dimethoxyphenyl)-3,4-dihydropyrimidin-2(1H)-
imine (16): IR (KBr): 3371, 3134, 2975, 1641 cmꢁ1 1H NMR (300 MHz,
:
MeOH-d4): d 1.64 (s, 3H, Ar-CH3-40), 1.69 (t, J = 7.9 Hz , 3H, CH3-10), 2.40 (s,
3 H, CH3-7), 5.47(s, 1H, CH-4), 3.27 (s, 1H, =NH-2), 3.35 (q, J = 7.9, 4.4 Hz,
2H, CH2O-9), 7.30–7.23 (m, 5H, Ar-H), 7.31 (s, 1H, NH-3),9.97 (s, 1H, NH-1),
Anal. Calcd for C16H21N3O4: C, 60.17; H, 6.63; N, 13.16. Found C, 60.21; H,
6.65; N, 13.14.
5-Ethoxycarbonyl- 6-methyl-4-phenyl- 3,4- dihydropyrimidin-2(1H)-imine (13):
IR (KBr): 3340, 3287, 2875, 1641 cmꢁ1 1H NMR (300 MHz, MeOH-d4): d 1.16
:
(t, J = 7.1 Hz , 3H, CH3-10), 2.33 (s, 3 H, CH3-7), 3.34 (s, 1H, NH-2), 4.08 (q,
J = 7.1, 4.8 Hz, 2H, CH2O-9), 5.30 (s, 1H, CH-4), 7.30–7.23 (m, 5H, Ar-H), 8.48
(s,1H, NH-3), 9.48 (s, 1H, NH-1)., MS: m/z 259 (M+ C14H17N3O2, 46%), 217 (25),
214 (100), 186 (13), 172 (16), 144 (18). Anal. Calcd for C14H17N3O2: C, 64.85; H,
6.61; N, 16.21. Found: C, 64.82; H, 6.63; N, 16.24.
5-Ethoxycarbonyl-6-methyl-4-(4-N,N-dimethylamino)-3,4-dihydropyrimidin-
2(1H)-imine (17): IR (KBr): 3319, 3114, 2965, 1650 cmꢁ1
:
1H NMR
(300 MHz, MeOH-d4):
d , 3H,
1.64 (s, 3H, Ar-CH3-40), 1.69 (t, J = 7.9 Hz
CH3-10), 2.40 (s, 3 H, CH3-7), 5.47 (s, 1H, CH-4), 3.27 (s, 1H, =NH-2), 3.35 (q,
J = 7.9, 4.4 Hz, 2H, CH2O-9), 8.21 (s, 1H, NH-1), 9.48 (s, 1H, NH-3), 7.30–7.23
(m, 5H, Ar-H); Anal. Calcd for C16H22N4O2: C, 63.55; H, 7.33; N, 18.53.
Found C, 63.53; H, 7.29; N, 18.49.
5-Ethoxycarbonyl-6-methyl-4-(4-methylphenyl)-3,4-dihydropyrimidin-2(1H)-
imine (14): IR (KBr): 3219, 3115, 2965, 1641 cmꢁ1
:
1H NMR (300 MHz,
MeOH-d4): d 1.64 (s, 3H, Ar-CH3-40), 1.69 (t, J = 7.9 Hz, 3H, CH3-10), 2.40 (s,