Revisit to the Biginelli reaction: A novel and recyclable bioglycerol-based sulfonic acid functionalized carbon catalyst for one-pot synthesis of substituted 3,4-dihydropyrimidin-2-(1H)-ones

Article abstract of DOI:10.1016/j.tetlet.2012.02.018

A simple and efficient synthetic protocol has been developed for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones by using a novel bioglycerol-based sulfonic acid functionalized carbon catalyst, devoid of moisture sensitive metal catalysts and corrosive acidic reagents. The developed method has the advantages of good to excellent yields, short reaction times, operational simplicity, and a recyclable catalyst. The catalyst can be prepared by a simple procedure from inexpensive and readily available glycerol and has been shown to be recoverable and reusable up to four cycles without any loss of activity.

Full text of DOI:10.1016/j.tetlet.2012.02.018

Tetrahedron Letters 53 (2012) 1968–1973
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Revisit to the Biginelli reaction: a novel and recyclable bioglycerol-based
sulfonic acid functionalized carbon catalyst for one-pot synthesis of substituted
3,4-dihydropyrimidin-2-(1H)-ones
Karnakar Konkala a, Narayana Murthy Sabbavarapu a, Ramesh Katla a, Nageswar Yadavalli Venkata Durga a,
,
⇑
Vijai Kumar Reddy T b, Bethala L.A. Prabhavathi Devi b, Rachapudi B.N. Prasad b
a Natural Product Chemistry, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500 007, India
b Centre for Lipid Research, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and efficient synthetic protocol has been developed for the synthesis of 3,4-dihydropyrimidin-2-
(1H)-ones by using a novel bioglycerol-based sulfonic acid functionalized carbon catalyst, devoid of mois-
ture sensitive metal catalysts and corrosive acidic reagents. The developed method has the advantages of
good to excellent yields, short reaction times, operational simplicity, and a recyclable catalyst. The cata-
lyst can be prepared by a simple procedure from inexpensive and readily available glycerol and has been
shown to be recoverable and reusable up to four cycles without any loss of activity.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 17 October 2011
Revised 1 February 2012
Accepted 4 February 2012
Available online 11 February 2012
Keywords:
Carbon catalyst
Bioglycerol
Biginelli reaction
Aldehydes
1,3-Diketones
Multi-component reactions (MCRs)1 are important synthetic
tools that can be useful in the preparation of biologically active
compounds.2 The Biginelli reaction allows access to dihydropyri-
midinones (DHPMs), central features of compounds with antiviral,
antitumor, antibacterial, cytotoxic, and antiflammatory proper-
ties.3 Some DHPMs possess remarkable pharmacological efficiency,
demonstrated by their utility as the integral backbone of calcium
channel blockers.4 Notably, the anticancer agent Monastrol is the
only cell-permeable molecule currently known to specifically inhi-
bit mitotic kinesin Eg5.5 DHPMs also feature prominently in SQ
32547 and SWO2, which have been identified as potent orally ac-
tive antihypertensive agents (Fig. 1).6 In addition, several alkaloids
isolated from marine sources containing the dihydropyrimidine
core unit have shown interesting biological properties.7 In particu-
lar, Batzelladine alkaloids have been found to be potent HIV gp-
120-CD4 inhibitors.8 Therefore, the synthesis of dihydropyrimidi-
none derivatives has gained prominence in synthetic organic as
well as medicinal chemistry.
Br
N
HO
F3C
O
O
N
EtOOC
H3C
i-PrOOC
EtOOC
H3C
NH
N
O
F
NH
O
H3C
N
H
N
H
S
OMe
O
Monastrol
SQ 32547
SWO2
Figure 1. Biologically active dihydropyrimidinones.
HO
S
O
R
3
SO H
3
X
O
O
HO
S
R2
NH
X
3
R-CHO
MeCN, 75-80 0
C
R1
R2
H2N
NH2
R1
N
H
R = Aryl, Hetero aryl ; X= O, S
R1 = CH3, Ph, Et, CF3; R2 = CH3, Ph, Et, OEt, OMe, OBn,
The Biginelli reaction, originally described by the Italian chem-
ist Pietro Biginelli9 in 1893, involves a one-pot condensation of an
aldehyde, a b-ketoester, and urea or thiourea under strongly acidic
conditions. The harsh reaction conditions, longer reaction times,
Scheme 1. Synthesis of 3,4-dihydropyrimidin-2-(1H)-ones catalyzed by bio-glyc-
erol based carbon catalyst.
and lower yields when using substituted aromatic and aliphatic
aldehydes are the main drawbacks. Hence the original Biginelli
condensation may not be suitable for compounds with sensitive
functional groups.
⇑
Corresponding author. Fax: +91 40 27160512.
E-mail address: dryvdnageswar@gmail.com (N.Y.V. Durga).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2012.02.018

K. Konkala et al. / Tetrahedron Letters 53 (2012) 1968–1973
1969
Table 1
Bioglycerol based carbon catalyst mediated synthesis of dihydropyrimidinonesa
Entry
Aldehyde
CHO
1,3-Diketone
X
O
Product
Time (h)
Yieldb (%)
O
O
O
O
O
O
EtO
EtO
EtO
EtOOC
1
4
90
83
NH
N
H
O
CHO
EtOOC
EtOOC
2
3
S
4
4
NH
N
H
S
CHO
CHO
OCH3
H3CO
O
92
NH
N
H
O
O
O
OCH3
EtO
H3CO
PhO
4
5
6
S
4
4
4
87
92
87
EtOOC
EtOOC
NH
N
H
S
O
O
O
O
OPh
CHO
EtO
EtO
O
O
NH
N
H
O
CHO
O
O
EtOOC
EtOOC
EtOOC
NH
N
H
O
CHO
O
O
O
O
Ph
EtO
EtO
Ph
7
O
4
88
NH
N
H
O
CHO
OCH3
OCH3
H3CO
H3C
OCH3
8
9
O
O
O
4
4
4
92
88
NH
N
H
O
CHO
CH3
O
O
O
O
H3C
EtO
EtO
CH3
NH
EtOOC
N
H
O
CHO
OCH3
OCH3
H3CO
OCH3
OCH3
H3CO
10
92
EtOOC
NH
N
H
O
(continued on next page)

1970
K. Konkala et al. / Tetrahedron Letters 53 (2012) 1968–1973
Table 1 (continued)
Entry
Aldehyde
CHO
1,3-Diketone
X
O
Product
Time (h)
Yieldb (%)
O
O
EtO
EtOOC
11
12
4
89
NH
N
H
O
CHO
O
O
EtO
O
O
O
S
4
89
91
82
83
EtOOC
EtOOC
EtOOC
NH
N
H
O
CHO
CHO
CHO
O
O
O
O
O
O
OH
EtO
EtO
EtO
HO
13
14
15
4
NH
N
H
O
NO2
O2N
4.5
4.5
NH
N
H
O
EtOOC
NH
N
H
S
O
O
EtO
O
O
CHO
16
17
O
O
4
4
87
90
EtOOC
NH
N
H
O
O
O
O
O
S
CHO
S
S
EtO
EtO
EtOOC
NH
N
H
O
S
S
CHO
S
18
19
O
4
85
EtOOC
NH
N
H
O
CHO
O
O
O
O
F
EtO
EtO
F
EtOOC
EtOOC
O
O
4
4
80
84
NH
N
H
O
CHO
Cl
20
Cl
NH
N
H
O
a
Reaction conditions: aldehyde (1.0 mmol), 1,3-diketone (1.0 mmol), urea/thiourea (1.5 mmol), and bioglycerol-based carbon catalyst (10 wt % of aldehyde) at 75–80 °C.
Isolated yields.
b

K. Konkala et al. / Tetrahedron Letters 53 (2012) 1968–1973
1971
Table 2
Bioglycerol based carbon catalyst mediated synthesis of Dihydropyrimidinonesa
Entry
Aldehyde
CHO
1,3-Diketone
X
O
Product
Time (h)
Yieldb (%)
O
O
H3COC
1
4
87
89
85
83
84
88
80
81
NH
N
H
O
CHO
CHO
CHO
CHO
CHO
CHO
CHO
O
O
O
O
MeO
BnO
MeOOC
BnOOC
2
3
4
5
6
7
8
O
O
O
O
O
O
O
4
4
4
4
4
4
4
NH
N
O
H
NH
N
H
O
O
O
Et
Et
EtOC
Et
NH
N
H
O
O
O
Ph
Ph
PhOC
Ph
NH
N
O
H
O
O
EtO
O
CF3
EtOOC
F3C
NH
N
O
H
O
O
NH
N
O
H
O
O
O
NH
N
H
O
a
Reaction conditions: aldehyde (1.0 mmol), 1,3-diketone (1.0 mmol), urea/thiourea (1.5 mmol), and bioglycerol-based carbon catalyst (10 wt % of aldehyde) at 75–80 °C.
Isolated yields.
b
Table 3
OCH3
Recyclability of Bioglycerol-based carbon catalyst
CHO
HO3S
HO3S
Cycles
Yield (%)
Catalyst recovered (%)
S
SO3H
O
O
O
Native
90
88
85
83
95
92
89
87
HN
NH2
MeCN, 75-800C
OEt
1
2
3
EtO
NH
OCH3
N
S
using heterogeneous catalysts.16 Among the most preparatively
useful of these is the use of acidic resins such as Indion-130, Naf-
ion-H, Nafion-NR-50, Amberlyst-15, or Amberlyst-70.17
Given the low cost and simple protocols involved in their prep-
aration, carbon-based solid acids could provide an appealing op-
tion to the sulfonic acid resins as heterogeneous catalysts for the
Biginelli reaction. In recent years carbon-based solid acid
Scheme 2. Biginelli condensation using Glycerol based carbon catalyst.
This shortcoming has been addressed in several ways, including
the use of Lewis Acids, milder protic acids,10 microwave irradia-
tion,11 ultrasound,12 ionic liquids,13 organocatalysis,14 and a com-
bination of these.15 Further efforts have focused on making these
reactions both substrate-tolerant and operationally simple by

1972
K. Konkala et al. / Tetrahedron Letters 53 (2012) 1968–1973
(a)
(b)
Figure 2. SEM images of (a) fresh bioglycerol-based carbon catalyst and (b) bioglycerol-based carbon catalyst after the fourth cycle.
catalysts18 have gained prominence due to their significant advan-
tages over homogeneous liquid phase mineral acids, such as in-
creased activity and selectivity, longer catalyst life, negligible
equipment corrosion, ease of product separation, and reusability.
These carbon-based catalysts, obtained by the incomplete carbon-
ization of sulfoaromatic hydrocarbons and consisting of small
polycyclic aromatic carbon sheets with attached SO3H groups,
have proven to be highly active in the esterification of fatty acids.
Prabhavathi et al reported preparing a similar sulfonic acid-
functionalized polycyclic aromatic carbon catalyst from bioglycer-
ol (biodiesel by-product) and also from glycerol-pitch (waste from
fat splitting industry) by in situ partial carbonization and sulfona-
tion.19 Such catalysts have been shown to be inexpensive, highly
stable, robust, recyclable, and easily produced from naturally avail-
able bio-glycerol, and are demonstrated to be effective for the
esterification, THP protection, and deprotection of alcohols and
phenols.20
In continuation of our interest towards the development of no-
vel heterocyclic compounds,21 we describe a simple but effective
one-pot, three-component method for the condensation of alde-
hydes, urea/thiourea, and 1,3-dicarbonyl compound to synthesize
the 3,4-dihydropyrimidin-2(1H)-ones in moderate to high yields,
using glycerol-based carbon catalyst.22 (Scheme 1) After optimizing
the experimental conditions, benzaldehyde (1.0 mmol), ethyl ace-
toacetate (1.0 mmol), and urea (1.5 mmol) were reacted in the pres-
ence of recyclable bioglycerol-based carbon catalyst (10 wt %
relative to benzaldehyde) in refluxing acetonitrile, resulting in the
formation of the desired dihydropyrimidinone in a 90% yield (Table
1, entry 1). To study the scope of this method, a variety of substi-
tuted aldehydes were used in this reaction process, resulting in a
range of diverse dihydropyrimidinones. Aromatic aldehydes carry-
ing either electron donating (Table 1, entries 3–5, 8–10, and 13) or
electron withdrawing (Table 1, entries 14, 19, 20) substituents re-
acted very well, affording moderate to high yields of DHPMs (Table
1). Acid-sensitive aldehydes such as 2-thiophenecarboxaldehyde
reacted well and gave the corresponding dihydropyrimidinone in
a 90% yield (Table 1, entry 17). The position of substituents on the
aromatic aldehydes had no impact, with ortho-, meta-, and para-
substituted aldehydes all performing similarly, and bulky alde-
hydes (Table 1, entries 7, 11, 12) reacted as well as those that were
less hindered. Hetero aromatic aldehydes containing benzofuran,
thiophene, and bithiophene also gave good yields (Table 1, entries
16, 17, 18). Yields were slightly diminished by either the introduc-
tion of a halogen onto the aromatic ring (Table 1, entries 19, 20) or
by replacing urea with thiourea (Table 1, entries 2, 4, 15).
high, with acetyl acetone, methyl acetoacetate, and ethyl 4,4,4-tri-
fluoroacetoacetate (entries 1, 2 and 6) performing the best.
This protocol was extended a step further, using allyl thiourea
as the urea component (Scheme 2). This provided the desired
3,4-dihydropyrimidin-2(1H)-thione in good yield (78%). All prod-
ucts were confirmed by spectroscopic techniques.23
To demonstrate the recyclability of the catalyst, after each cycle
the reaction mixture was allowed to cool and the catalyst was
recovered by simple filtration, washed with ethyl acetate and ace-
tone and dried under reduced pressure. The catalyst was reused for
the same reaction without further activation. The reaction pro-
ceeded smoothly even after three cycles, without any extension
of reaction time or marked loss in yield (Table 3). The SEM images
of the bio-glycerol based carbon catalyst, before and after the reac-
tion, are provided in Figure 2.
The recyclability of the bioglycerol-based carbon catalyst was
examined by using benzaldehyde (1.0 mmol), ethyl acetoacetate
(1.0 mmol), and urea (1.5 mmol) in MeCN (10 mL), as a model
reaction.
In conclusion, we have developed a novel and reusable bioglyc-
erol-based carbon catalyst for an efficient one-pot three-compo-
nent synthesis of 3,4-dihydropyrimidinones. The salient features
of the present protocol are easy work-up, recyclability of the bio-
glycerol-based carbon catalyst, and good yields. The present proto-
col offers a simple, inexpensive, and versatile approach to the
synthesis of sterically demanding DHPMs.
Acknowledgments
We thank the CSIR, New Delhi, India, for fellowships to K.K,
S.N.M., T.V.K.R. and the UGC for fellowship to KR.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2012.02.018.
References and notes
1. (a) Bienayme, H.; Hulme, C.; Oddon, G.; Schmitt, P. Chem. Eur. J. 2000, 6, 3321–
3329; (b) Domling, A.; Ugi, I. Angew. Chem., Int. Ed. 2000, 39, 3168–3210.
2. (a) Dolle, R. E.; Nelson, K. H., Jr. J. Comb. Chem. 1999, 1, 235–282; (b) Nuss, J. M.;
Renhowe, P. A. Curr. Opin. Drug Discovery. Dev. 1999, 2, 631–650; (c) Oliver, S.
F.; Abell, C. Curr. Opin. Chem. Biol. 1999, 3, 299–306; (d) Thompson, L. A.;
Ellman, J. A. Chem. Rev. 1996, 96, 555–600.
3. Dihydropyrimidine calcium channel modulators: (a) Atwal, K. S.; Swanson, B.
N.; Unger, S. E.; Floyd, D. M.; Moreland, S.; Hedberg, A.; O’Reilly, B. C. J. Med.
Chem 1991, 34, 806; (b) Kappe, C. O. QSAR Comb. Sci. 2003, 22, 630.
The same reaction conditions were then applied to a range of
1,3-dicarbonyl compounds (Table 2). The yields were consistently

K. Konkala et al. / Tetrahedron Letters 53 (2012) 1968–1973
1973
4. (a) Ronyar, G. C.; Kinball, S. D.; Beyer, B.; Cucinotta, G.; Dimarco, J. D.;
Gougoutas, J.; Hedberg, A.; Malley, M.; McCarthy, J. P.; Zhang, R.; Moreland, S. J.
Med. Chem. 1995, 38, 119; (b) Aswal, K. S.; Rovnyak, G. C.; Kinball, S. D.; Floyd,
D. M.; Moreland, S.; Swanson, B. N.; Gougoutas, J. Z.; Schwartz, J.; Smillie, K. M.;
Mallay, M. F. J. Med. Chem. 1990, 33, 2629.
Toda, M.; Okamura, M.; Kondo, J. N.; Hayashi, S.; Domen, K.; Hara, M. Catal.
Today 2006, 116, 157–161; (d) Zong; M. H. Duan, Z. Q.; Lou, W. Y.; Smith, T. J.;
Wu, H. Green Chem. 2007, 9, 434–437.
19. Prabhavathi Devi, B. L. A.; Gangadhar, K. N.; Sai Prasad, P. S.; Jagannadh, B.;
Prasad, R. B. N. ChemSusChem 2009, 2, 617–620.
5. (a) Mayer, T. M.; Kapoor, T. M.; Haggarty, S. J.; King, R. W.; Schreiber, S. L.;
Mitchison, T. J. Science 1999, 286, 971; (b) Kappe, C. O.; Shishkin, O. V.; Uray, G.;
Verdino, P. Tetrahedron 2000, 56, 1859.
20. Prabhavathi Devi, B. L. A.; Gangadhar, N.; Siva Kumar, K. L. N.; Shiva Shanker,
K.; Prasad, R. B. N.; Sai Prasad, P. S. J. Mol. Catal. A: Chem. 2011, 345, 96–100.
21. (a) Murthy, S. N.; Madhav, B.; Kumar, A. V.; Rao, K. R.; Nageswar, Y. V. D. Helv
Chim. Acta. 2009, 92, 2118; (b) Murthy, S. N.; Madhav, B.; Kumar, A. V.; Rao, K.
R.; Nageswar, Y. V. D. Tetrahedron 2009, 65, 5251; (c) Madhav, B.; Murthy, S. N.;
Reddy, V. P.; Rao, K. R.; Nageswar, Y. V. D. Tetrahedron Lett. 2009, 50, 6025; (d)
Murthy, S. N.; Madhav, B.; Reddy, V. P.; Nageswar, Y. V. D. Tetrahedron Lett.
2010, 51, 3649; (e) Shankar, J.; Karnakar, K.; Srinivas, B.; Nageswar, Y. V. D.
Tetrahedron Lett. 2010, 51, 3938; (f) Murthy, S. N.; Madhav, B.; Nageswar, Y. V.
D. Tetrahedron. Lett. 2010, 51, 5252; (g) Ramesh, K.; Murthy, S. N.; Nageswar, Y.
V. D. Tetrahedron. Lett. 2011, 52, 2362; (h) AnilKumar, B. S. P.; Madhav, B.;
Harsha Vardhan Reddy, K.; Nageswar, Y. V. D. Tetrahedron. Lett. 2011, 52, 2862.
22. Experimental:
6. Kappe, C. O. Eur. J. Med. Chem. 2000, 35, 1043–1052.
7. Butters, M.; Davies, C. D.; Elliott, M. C. Org. Biomol. Chem. 2009, 7, 5001–5009.
8. (a) Heys, L.; Moore, C. G.; Murphy, P. J. Chem. Soc. Rev. 2000, 29, 57; (b)
Barluenga, J.; Tomas, M.; Rubio, V.; Gotor, V. J. Chem. Commun. 1995, 1369; (c)
Aron, Z. D.; Overman, L. E. Chem. Commun. 2004, 253.
9. Biginelli, P. Gazz. Chem. Ital. 1893, 23, 360.
10. (a) Kumar, K. A.; Kasthuraiah, M.; Reddy, C. S.; Reddy, C. D. Tetrahedron Lett.
2001, 42, 7873–7874; (b) Russowsky, D.; Lopes, F. A.; Da Silva, V. S.; Canto, K. F.
S.; Montes D’Oca M. G.; Godoi, M. N. J. Brazil Chem. Soc. 2004, 15, 165; (c) De, S.
K.; Gibbs, R. A. Synthesis 2005, 1748; (d) Han, X.; Xu, F.; Luo, Y.; Shen, Q. Eur. J.
Org. Chem. 2005, 1500; (e) Reddy, C. V.; Mahesh, M.; Raju, P. V. K.; Babu, T. R.;
Reddy, V. V. N. Tetrahedron Lett. 2002, 43, 2657; (f) Lu, J.; Ma, H. R. Synlett 2000,
63.
11. (a) Kappe, C. O.; Kumar, D.; Varma, R. S. Synthesis 1999, 1799; (b) Banik, B. K.;
Reddy, A. T.; Datta, A.; Mukhopadhyay, C. Tetrahedron Lett. 2007, 48, 7392–
7394.
12. Li, J. T.; Han, J. F.; Yang, J. H.; Li, T. S. Ultrason. Sonochem. 2003, 10, 119–122.
13. Peng, J.; Deng, Y. Tetrahedron Lett. 2001, 42, 5917–5919.
14. Verma, S.; Jain, S. L.; Sain, B. Tetrahedron Lett. 2010, 51, 6897–6900.
15. Pasunooti, K. K.; Chai, H.; Jensen, C. N.; Bala Kishan, G.; Wang, S.; Liu, X.-W.
Tetrahedron Lett. 2011, 52, 80–84.
General procedure for the synthesis of substituted 3,4-dihydropyrimidne-2(1H)-
ones/thiones: To a stirred solution of aldehyde (1.0 mmol) and 1,3-diketone
(1.0 mmol) in MeCN (10 mL) containing bioglycerol-based carbon catalyst
(10 wt % of aldehyde), urea/thiourea (1.5 mmol) was added and heated to
reflux under nitrogen atmosphere at 75–80 °C, until the reaction was complete
as indicated by TLC. After completion of the reaction, the catalyst was
separated by filtration and washed with ethyl acetate/acetone for reuse. The
reaction mixture was concentrated to remove MeCN. After the evaporation of
the solvent under reduced pressure, the crude residue was extracted with
EtOAc and the combined organic layers were washed with brine solution, dried
over anhydrous Na2SO4, evaporated to get the crude product, which was
purified by column chromatography, using hexane and EtOAc as eluent to give
the title compound.
16. Peng, Li; Sridhar, R.; Butcher, R. J.; Arman, H. D.; Chen, Z.; Shengchang, Xi; Chen,
B.; Zhao, C.-G. Tetrahedron Lett. 2011, 52, 6220–6222.
17. (a) Pansuriya, A. M.; Savant, M. M.; Bhuva, C. V.; Kapuriya, N.; Singh, J.;
Naliapara, Y. T. Lett. Org. Chem. 2009, 6, 619–623; Lin, H.; Zhao; Qi; Xu, B.;
Wang, Xi J. Mol. Catal. A: Chem. 2007, 268, 221–226; (c) Wang, Q.; Pei, W. J. Iran.
Chem. Soc. 2010, 7, 318–321; (d) Polshettiwar, V.; Varma, R. S. Tetrahedron Lett.
2007, 48, 7343–7346; (e) Tajbakhsh, M.; Mohajerani, B.; Heravi, M. M.;
Ahmadi, A. N. J. Mol. Catal. A: Chem. 2005, 236, 216–219; (f) Bigi, F.; Carloni, S.;
Frullanti, B.; Maggi, R.; Sartori, G. Tetrahedron Lett. 1999, 40, 3465–3468; (g)
Chandak, H. S.; Lad, N. P.; Upare, P. P. Catal. Lett. 2009, 131, 469–473; (h) Kappe,
C. O. Synlett 1998, 718–720; (i) Lin, H. X.; Zhao, Q. J.; Wang Xi, H. Chin. Chem.
Lett. 2007, 18, 502–504; (j) Joseph, J. K.; Jain, S. L.; Sain, B. J. Mol. Catal. A: Chem.
2006, 247, 99–102.
23. Data for representative examples
Ethyl
(Table 1, entry 1)20: white solid, mp 201–203 °C. IR (KBr) 3244, 3109, 2933,
1710, 1650, 1222, 1089 cmÀ1 1H NMR (300 MHz, CDCl3 + DMSO-d6, TMS)
6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate
;
d = 9.11 (s, 1H), 7.66 (s, 1H), 7.20–7.31 (m, 5H), 5.17 (d, J = 3.8 Hz, 1H), 3.98 (q,
J = 7.6 Hz, 2H), 2.26 (s, 3H), 1.11 (t, J = 7.6 Hz, 3H) ppm. 13C NMR (75 MHz,
CDCl3 + DMSO-d6, TMS) d 165.0, 152.0, 147.9, 144.7, 127.9, 126.8, 126.0, 106.2,
58.8, 53.9, 17.5, 13.8 ppm. ESI-MS: 261 (M+H)+; C14H17N2O3.
Ethyl
(Table 1, entry 2)16: light yellow solid, mp 205–207 °C. IR (KBr) 3240, 3111,
2928, 1710, 1647, 1220, 1086 cmÀ1 1H NMR (300 MHz, CDCl3 + DMSO-d6,
6-methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
;
18. (a) Hara, M.; Yoshida, T.; Takagaki, A.; Takata, T.; Kondo, J. N.; Hayashi, S.;
Domen, K. Angew. Angew. Chem., Int. Ed. 2004, 116, 3015–3018. Angew. Chem.,
Int. Ed., 2004, 43, 2955–2958; (b) Toda, M.; Takagaki, A.; Okamura, M.; Kondo, J.
N.; Hayashi, S.; Domen, K.; Hara, M. Nature 2005, 438, 178; (c) Takagaki, A.;
TMS) d = 10.10 (s, 1H), 7.21–7.34 (m, 5H), 6.01 (s, 1H), 5.19 (d, J = 3.6 Hz, 1H),
4.02 (q, J = 6.9 Hz, 2H), 2.28 (s, 3H), 1.18 (t, J = 6.9 Hz, 3H) ppm. 13C NMR
(75 MHz, CDCl3 + DMSO-d6, TMS) d 174.0, 166.5, 158.4, 144.7, 127.9, 126.8,
126.5, 106.0, 58.8, 56.8, 17.9, 13.7 ppm. ESI-MS: 277 (M+H)+; C14H17N2O2S.