Microwave-assisted multicomponent reaction of aryl amidines: Regiospecific synthesis of new polysubstituted thiopyrano-, and pyrano[4,3-d]pyrimidines

Article abstract of DOI:10.1016/j.tetlet.2011.12.128

A series of new functionalized thiopyrano-, pyrano[4,3-d]pyrimidine derivatives with benzyl group residing in 8-position of fused pyrimidine nucleus were synthesized through multicomponent reactions of aromatic aldehydes, tetrahydrothiopyran-4-one(tetrahy

Full text of DOI:10.1016/j.tetlet.2011.12.128

Tetrahedron Letters 53 (2012) 1261–1264
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Microwave-assisted multicomponent reaction of aryl amidines: regiospecific
synthesis of new polysubstituted thiopyrano-, and pyrano[4,3-d]pyrimidines
⇑
⇑
Bo Jiang , Li-Yuan Xue, Xing-Han Wang, Man-Su Tu, Yin-Ping Liu, Shu-Jiang Tu
School of Chemistry and Chemical Engineering, Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Xuzhou Normal University, Xuzhou 211116, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of new functionalized thiopyrano-, pyrano[4,3-d]pyrimidine derivatives with benzyl group
residing in 8-position of fused pyrimidine nucleus were synthesized through multicomponent reactions
of aromatic aldehydes, tetrahydrothiopyran-4-one(tetrahydropyran-4-one), and aryl amidines using
t-BuOK as a base under microwave heating. The procedure is facile, avoiding time-consuming and costly
syntheses, tedious work-up, and purifications of precursors as well as protection/deprotection of func-
tional groups. This method is very efficient due to short reaction times and easy work up and provides a
four-component strategy for the construction of the thiopyrano-, and pyrano[4,3-d] pyrimidine skeletons.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 6 October 2011
Revised 27 December 2011
Accepted 30 December 2011
Available online 10 January 2012
Keywords:
Multicomponent reaction
Thiopyrano[4,3-d]pyrimidines
Pyrano[4,3-d]pyrimidines
Regioselectivity
Microwave heating
The search for the efficient formations of multifunctionalized
complex products by using simple reactants has been an active
objective in organic synthesis.1 In this regard, multi-component
domino reactions that are very useful for the total syntheses of
natural products and versatile building blocks have become
increasingly attractive because of their green characteristics of
atom-economy, bond-forming economy, and structural economy.2
These reactions can avoid time-consuming and costly processes for
the purification of various precursors and tedious steps of protec-
tion and deprotection of functional groups. In addition, these reac-
tions are environmentally friendly, and often proceed with
excellent chemoselectivities.3 Therefore; the design of new selec-
tive multi-component domino reactions is a continuing challenge
at the forefront of organic chemistry.
has attracted considerable attention.13 In the other hand, amidines
and related compounds possessing 1,3-binucleophilic centers arAe
versatile synthetic intermediates in organic chemistry.14 They are
frequently applied in the preparation of pyrimidine-containing het-
erocycles.14,15 Many pyrimidines have been synthesized by the
reactions of amidines, aldehydes, and appropriate ketones via vari-
ous methods.15 However, most of these compounds belong to
pyrimidines I15a,b or fused pyrimidines II15c–e (Fig. 1). To the best
of our knowledge, the construction of pyrano- or thiopyrano[4,3-
d]pyrimidine skeleton (type III) with benzyl group regiospecifically
residing in 8-position of fused pyran (thiopyran) nucleus has not
been reported so far.
Over the past several years, our group has developed various
domino reactions that can offer easy access to useful functional-
ized multiple ring structures of chemical and pharmaceutical inter-
est.16 For example, a new four-component domino reaction was
established as to provide an easy access to the synthesis of multi-
functionalized quinazoline16a and tricyclo[6.2.2.01,6]dodecanes
derivatives.16b Recently, we have also found that the domino
reaction of Meldrum’s acid, aromatic aldehydes, and electron-rich
Pyrimidines compose an important class of heterocycles4 and
their structural framework is a key constituent of numerous natural
biologically active compounds.5 The pyrano-fused pyrimidines as a
key pyrimidine family showed a broad range of biological activities,
such as antitubercular and antimicrobial agents,6 antimicrobial
agent,7 and antiplatelet,8 antifungal agents9 as well as antiviral
activities.10 In the other hand, the thiopyrano-fused pyrimidines
also exhibited antidiabetic11 and hypoglycemic12 activities. Because
of these biological activities they exhibit, these compounds have
distinguished themselves as heterocycles of profound chemical
and biological significance. Thus the synthesis of these molecules
O
R
Ar
Ar
O
Ar
N
N
X
N
N
H
I
Ar'
Ar'
Ar'
N
N
H
II
III
Ar
⇑
Corresponding authors. Tel./fax: +86 516 83500065.
E-mail addresses: jiangchem@xznu.edu.cn (B. Jiang),
laotu2001@263.net,
Figure 1. The synthesis of structurally diverse pyrimidines via the reaction of
laotu@xznu.edu.cn (S.-J. Tu).
arylamidines, aldehydes, and different ketones.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.12.128

1262
B. Jiang et al. / Tetrahedron Letters 53 (2012) 1261–1264
Table 1
heteroaryl-amines in aqueous phase under microwave irradiation
(MW) led to the multifunctionalized spiro{[1,3]dioxanes-pyri-
dine}-4,6-dione with high chemo- regio-, and stereoselectivities
and good yields.16c
As part of our continuing interest in the development of new
domino reaction in heterocyclic compounds,17,18 in this paper we
would like to report a new route to a set of fused pyrimidine deriv-
atives with benzyl group regiospecifically residing in 8-position of
fused pyran (thiopyran) nucleus. This reaction was achieved by
using readily available aromatic aldehydes 1, tetrahydrothiopy-
ran-4-one(tetrahydropyran-4-one) 2, and aryl amidines 3 under
microwave heating through one-pot four-component strategy
shown in Scheme 1.
Optimization of bases for the synthesis of 4a under MW
Ph
O
N
S
N
Ph
Ar
Base
MW
Ar
Ar
+
+
HN
2
NH2
Ο
S
1a
2a
3a
4a
Ar = 4-Chlorophenyl
a
Entry
Base
Equiv of base
Solvent
T (°C)
Yield (%)
1
2
3
4
5
6
7
8
NaOH
KOH
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
Glycol
Glycol
MeOH
EtOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
100
100
100
100
100
120
140
150
30
40
52
58
70
74
82
80
MeONa
EtONa
t-BuOK
t-BuOK
t-BuOK
t-BuOK
To optimize the reaction conditions for the formation of the tar-
get compounds, we started this study by treating 4-chlorobenzalde-
hyde (1a) and tetrahydrothiopyran-4-one (2a) with benzamidine
(3a) in a ratio of 2:1:1.1 under microwave irradiation. Various reac-
tion conditions were investigated, including bases, solvents, and
temperatures. Initially, we employed various bases to determine
one which can give the best results. The results of theses compara-
tive experiments are summarized in Table 1. It was found that with
alkaline enhancement of the reaction system, the yield of product
4a was improved (Table 1, entries 1–5). In this reaction t-BuOK
demonstrated superior activity and gave the 70% yield of 4a at
100 °C for 15 min. Subsequently, the reaction was performed in t-
BuOH and repeated many times at different temperatures in a
sealed vessel under microwave heating for 15 min. As shown in Ta-
ble 1, the yield of product 4a increased from 70% to 82% as the tem-
perature was raised from 100 to 140 °C (Table 1, entries 5–7).
However, the yields leveled off when the temperature was further
raised to 150 °C (Table 1, entry 8).
With this result in hand, we went on to study the scope of the
methodology. Under the optimized conditions, a variety of structur-
ally diverse aromatic aldehydes were investigated and a series of
new thiopyrano[4,3-d]pyrimidines with benzyl group regiospecifi-
cally residing in 8-position of fused thiopyran nucleus were affor-
ded in good yields. As shown in Table 2, at the beginning, we
explored the aldehyde substrate scope, using tetrahydrothiopy-
ran-4-one (2a) and benzamidine (3a) as model substrates (Table
2, entries 1–5). The results indicated that aromatic aldehydes bear-
ing either electron-donating or -withdrawing functional groups,
such as fluoro, chloro, or methoxy, were suitable for the synthesis
of compound 4. Moreover, the heterocyclic aldehyde thiophene-2-
carbaldehyde (Table 2, entry 6) still displayed high reactivity under
the standard conditions. It is noted that this result is significant
because there is no literature precedent for the synthesis of highly
functionalized thiopyrano[4,3-d]pyrimidines with high regiosele
ctivity.
a
Isolated yield.
Table 2
Multicomponent synthesis of fused pyrimidines 419
a
b
c
Entry
4
Ar
3
X
Time
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
4a
4b
4c
4d
4e
4f
4g
4h
4i
4-Chlorophenyl (1a)
4-Fluorophenyl (1b)
4-Methoxyphenyl (1c)
3,4-Dimethoxyphenyl (1d)
3,4,5-Trimethoxyphenyl (1e) 3a
3a
3a
3a
3a
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
O
O
O
O
O
15
16
16
14
13
17
14
15
15
14
17
15
16
14
13
16
12
17
16
17
15
82
83
90
83
81
88
83
85
82
81
79
84
87
80
86
79
86
89
86
84
83
2-Thienyl (1f)
3a
3b
3b
3b
3c
3c
3c
3c
4-Chlorophenyl (1a)
4-Fluorophenyl (1b)
4-Bromophenyl (1g)
4-Chlorophenyl (1a)
4-Fluorophenyl (1b)
4-Methoxyphenyl (1c)
4j
4k
4l
4m 3,4-Dimethoxyphenyl (1d)
4n
4o
4p
4q
4r
4s
4t
4u
3,4,5-Trimethoxyphenyl (1e) 3c
2-Thienyl (1f)
4-Toyl (1h)
4-Chlorophenyl (1a)
4-Fluorophenyl (1b)
Phenyl (1i)
4-Chlorophenyl (1a)
Phenyl (1i)
3c
3c
3a
3a
3a
3c
3c
a
b
c
Reagents and conditions: t-BuOK (2.0 equiv), 140 °C, t-BuOH (2.0 mL), MW.
Min.
Isolated yield.
To examine further scope of the methodology, tetrahydropyran-4-
one (2b) was employed to subject with aldehydes 1 and arylamidine 3
under the optimized conditions described above, the reactions
smoothly proceeded to generate the corresponding pyrano[4,3-
d]pyrimidine derivatives 4q–4u in good to excellent yields (Scheme
2; Table 2, entries 17–21).
The structures of all the products 4 were unambiguously char-
acterized by IR, 1H NMR, and HRMS (ESI). Furthermore, the struc-
ture of 4s was further established by an X-ray crystallographic
analysis (Fig. 2).18
To further expand the scope of the reaction, different aldehydes
and tetrahydrothiopyran-4-one (2a) were used as substrates with
4-chlorobenzimidamide (3b) and 4-bromobenzimidamide (3c). In
all these cases, the reactions proceeded smoothly to give the corre-
sponding thiopyrano[4,3-d]pyrimidines in good yields of 79–87%
(Table 2, entries 7–16). Indeed, the protocol provides a straightfor-
ward pathway for the construction of highly functionalized thio-
pyrano[4,3-d]pyrimidines.
Ar'
Ar'
O
O
N
N
N
N
Ar'
Ar'
Ar
Ar
t-BuOK / t-BuOH
NH2
MW
Base
MW
Ar
Ar
Ar
+
+
+
+
Ar
2
2
HN
NH2
HN
Ο
Ο
X
O
X
4
O
4q-4u
X = O, S
1
1
2
3
2b
3
Scheme 1. The multicomponent synthesis of fused pyrimidines.
Scheme 2. The synthesis of pyrano[4,3-d]pyrimidines.

B. Jiang et al. / Tetrahedron Letters 53 (2012) 1261–1264
1263
Acknowledgments
We are grateful for financial support from the National Science
Foundation of China (21072163, 21110102002, and 21102124),
PAPD of Jiangsu Higher Education Institutions, Science Foundation
in Interdisciplinary Major Research Project of Xuzhou Normal Uni-
versity (No. 09XKXK01), the NSF of Jiangsu Education Committee
(11KJB150016), Jiangsu Science and Technology Support Program
(No. BE2011045), and Doctoral Research Foundation of Xuzhou
Normal Univ. (XZNU, No. 10XLR20).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.12.128.
References and notes
Figure 2. X-ray crystallography structure of compound 4s.20
1. (a) New Avenues to Efficient Chemical Synthesis. Emerging Technologies,
Seeberger, P. H.; Blume, T., Eds.; Springer: Heidelberg, 2007 (Ernst Schering
Foundation Symposium Proceedings 2006–3).; (b) Nicolaou, K. C.; Yue, E. W.;
Oshima, T. In The New Chemistry; Hall, N., Ed.; Cambridge University Press:
Cambridge, 2001; pp 168–198; (c) Tietze, L. F.; Hautner, F. In Stimulating
Concepts in Organic Chemistry; Vgtle, F., Stoddart, J. F., Shibashaki, M., Eds.;
Wiley: Weinheim, 2000; pp 38–64.
2. Recent reviews on multicomponent reactions see: Groenendaal, (a) Ruijter, B.
E.; Orru, R. V. A. Chem. Commun. 2008, 5474; (b) Ismabert, N.; Lavila, R. Chem.-
Eur. J. 2008, 14, 8444; (c) Sunderhaus, J. D.; Martin, S. F. Chem.-Eur. J. 2009, 15,
1300; (d) Ganem, B. Acc. Chem. Res. 2009, 42, 463; (e) Tietze, L. F.; Kinzel, T.;
Brazel, C. C. Acc. Chem. Res. 2009, 42, 367; (f) Estevez, V.; Villacampa, M.;
Menendez, J. C. Chem. Soc. Rev. 2010, 39, 4402; (g) Candeias, N. R.; Montalbano,
F.; Cal, P. M. S. D.; Gois, P. M. P. Chem. Rev. 2010, 110, 6169; (h) Toure, B. B.; Hall,
D. G. Chem. Rev. 2009, 109, 4439; (i) Jiang, B.; Rajale, T.; Walter, W.; Tu, S.-J.; Li,
G. Chem.-Asian J. 2010, 5, 2318; (j) Isambert, N.; Duque, M.; Del, M. S.;
Plaquevent, J.-C.; Genisson, Y.; Rodriguez, J.; Constantieux, T. Chem. Soc. Rev.
2011, 40, 1347.
Ar'
Ar'
Ar
O
O
2
HN
N
H2N
NH
O
Ar
Ar
3
1
Ar
Ar
[3+3] Cyclization
Base
X
X
2
X
B
A
X = S, O
1,5-Hydrogen Transfer
Ar'
Ar'
N
N
3. (a) Tietze, L. F. Chem. Rev. 1996, 96, 115; (b) Tietze, L. F.; Haunert, F. In
Stimulating Concepts in Chemistry; Votle, F., Stoddart, J. F., Shibasaki, M., Eds.;
Wiley: Weinheim, 2000; pp 39–64; (c) Enders, D.; Huttl, M. R. M.; Grondal, C.;
Raabe, G. Nature 2006, 861.
4. Brown, D. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C.
W., Eds.; Pergamon: Oxford, 1996. Vol. 3, Chapter 2.13.
HN
X
N
1,3-Hydrogen Transfer
Ar
Ar
Ar
Ar
X
B'
4
5. Lagoja, I. M. Chem. Biodiversity 2005, 2, 1.
6. Kamdar, N. R.; Haveliwala, D. D.; Mistry, P. T.; Patel, S. K. Eur. J. Med. Chem.
2010, 45, 5056–5063.
Scheme 3. Proposed mechanism for the formations of fused pyrimidines 4.
7. (a) Abdel Fattah, M. E.; Atta, A. H.; Abdel Gawad, I. I.; Mina, S. M. Orient. J. Chem.
2004, 20, 257; (b) Ghorab, M. M.; Hassan, A. Y. Phosphorus Sulfur Silicon 1998,
141, 251.
8. Bruno, O.; Brullo, C.; Ranise, A.; Schenone, S.; Bondavalli, F.; Barocelli, E.;
Ballabeni, V.; Chiavarini, M.; Tognolini, M.; Impicciatore, M. Bioorg. Med. Chem.
Lett. 2001, 11, 1397.
9. Akluwalia, V. K.; Bala, Madhu Indian J. Chem., Sect. B 1996, 35B, 742.
10. Shamroukh, A. H.; Zaki, M. E. A.; Morsy, E. M. H.; Abdel-Motti, F. M.; Abdel-
Megeid, F. M. E. Arch. Pharm. 2007, 340, 236.
11. Yen, T. T.; Dininger, N. B.; Broderick, C. L.; Gill, A. M. Arch. Int. Pharmacodyn.
Ther. 1990, 308, 137.
12. (a) Ohno, S.; Mizukoshi, K.; Komatsu, O.; Kuno, Y.; Nakamura, Y.; Kato, E.;
Nagasaka, M. Chem. Pharm. Bull. 1986, 34, 4150; (b) Ogawa, H.; Kunoh, Y.;
Sugiura, T.; Nagasaka, M. Life Sci. 1992, 50, 375.
13. (a) Majumdar, K. C.; Chattopadhyay, S. K. Can. J. Chem. 2006, 84, 469; (b)
Majumdar, K. C.; Jana, N. K.; Bandyopadhyay, A.; Ghosh, S. K. Synth. Commun.
2001, 31, 2979; (c) Assy, M. G.; Amer, A. M.; El-Bahaie, S.; Halima, E. A. Polish J.
Chem. 1998, 72, 61; (d) El-Bahaie, S.; Assy, M. G. J. Chin. Chem. Soc. 1990, 37,
497; (e) El-Bahaie, S. Pharmazie 1990, 45, 62.
14. (a) Perjesi, P.; Foldesi, A.; Tamas, J. Monatsh. Chem. 1993, 124, 167; (b) El-
Rayyes, N. R.; Al-Saleh, B.; Al-Omran, F. J. Chem. Eng. Data 1987, 32, 280.
15. (a) Zhu, X.; Zhao, G.; Zhou, X.; Xu, X.; Xia, G.; Zheng, Z.; Wang, L.; Yang, X.; Li, S.
Bioorg. Med. Chem. Lett. 2010, 20, 299; (b) Ahluwalia, V. K.; Gupta, Charu;
Khanduri, C. H. Indian J. Chem., Sect. B 1992, 31B, 355; (c) Weis, A. L.; Frolow, F. J.
Chem. Soc. Perkin Trans. 1 1986, 83; (d) Weis, A. L. Synthesis 1985, 528; (e) Kuno,
A.; Sugiyama, Y.; Katsuta, K.; Kamitani, T.; Takasugi, H. Chem. Pharm. Bull. 1992,
40, 1452.
16. (a) Jiang, B.; Tu, S.-J.; Kaur, P.; Wever, W.; Li, G. J. Am. Chem. Soc. 2009, 131,
11660; (b) Jiang, B.; Li, C.; Shi, F.; Tu, S.-J.; Kaur, P.; Wever, W.; Li, G. J. Org.
Chem. 2010, 75, 2962; (c) Ma, N.; Jiang, B.; Zhang, G.; Tu, S.-J.; Wever, W.; Li, G.
Green Chem. 2010, 12, 1357; (d) Cheng, C.; Jiang, B.; Tu, S.-J.; Li, G. Green Chem.
2011, 13, 2107.
A reasonable mechanism for the formation of 4 was proposed in
Scheme 3. The formation of 4 is expected to proceed via initial
condensation of aromatic aldehydes and heterocyclic ketones 2
to afford 2,6-dibenzylidene heterocyclic ketones A, and then the
[3+3] cycloaddition between A and aryl amidine 3 would provide
intermediate B, which undergoes sequential 1,5-, and 1,3-hydro-
gen transfer to afford the final products 4.
Besides a high efficiency in the formation of multiple bonds as a
domino process, this reaction has the following advantages: (1) the
starting materials are readily available and the reagents are not
expensive; (2) the convenient work-up which only needs simple fil-
tration since the products directly precipitate out after the reaction
system is neutralized with acid and when its mixtures are diluted
with cold water; (3) short reaction times; (4) the regiospecific con-
struction of fused pyrimidine derivatives with benzyl group resid-
ing in 8-position of thiopyranopyrimidine nucleus. The novelty of
the present multicomponent domino reaction is shown by the fact
that multiple chemical bonds breaking and forming were simulta-
neously achieved in an intermolecular manner and in a one-pot
operation.
In summary, new multi-component domino reactions for regio-
specific construction of polysubstituted thiopyrano- or pyranopyr-
imidine skeletons have been established. The reactions showed
high regioselectivity and broad substrate scope which further can
employ in a wide range of common commercial starting materials.
17. (a) Jiang, B.; Zhang, G.; Ma, N.; Shi, F.; Tu, S.-J.; Kaur, P.; Li, G. Org. Biomol. Chem.
2011, 9, 3834; (b) Jiang, B.; Wang, X.; Shi, F.; Tu, S.-J.; Li, G. Org. Biomol. Chem.
2011, 9, 4025; (c) Jiang, B.; Hao, W.-J.; Zhang, J.-P.; Tu, S.-J.; Shi, F. Org. Biomol.

1264
B. Jiang et al. / Tetrahedron Letters 53 (2012) 1261–1264
(4s) White solid, mp: 134–136 °C; IR (KBr,
Chem. 2009, 7, 1171; (d) Jiang, B.; Hao, W.-J.; Zhang, J.-P.; Tu, S.-J.; Shi, F. Org.
m
, cmÀ1): 3058, 3024, 2841,1541,
Biomol. Chem. 2009, 7, 2195; (e) Jiang, B.; Shi, F.; Tu, S.-J. Curr. Org. Chem. 2010,
14, 357.
1494, 1466, 1452, 1397, 1381, 1365, 1115, 1062, 954, 920, 756, 696; 1H NMR
(400 MHz, DMSO-d6) (d ppm): 8.46–8.44 (m, 2H, ArH), 7.73–7.71 (m, 2H, ArH),
7.58–7.55 (m, 3H, ArH), 7.54–7.53 (m, 3H, ArH), 7.37–7.32 (m, 4H, ArH), 7.28–
7.23 (m, 1H, ArH), 4.96–4.76 (m, 2H, CH2), 3.92–3.88 (m, 1H, CH2), 3.82–3.78 (m,
1H, CH2), 3.47–3.43 (m, 1H, CH2), 3.31–3.26 (m, 1H, CH2), 2.92–2.86 (m, 1H, CH);
13C NMR (100 MHz, DMSO-d6) (d ppm): 165.9, 162.0, 161.3, 139.5, 137.2, 137.0,
130.6, 129.8, 129.1, 128.7, 128.5, 128.5, 128.4, 127.7, 126.2, 123.8, 67.2, 65.5,
41.4, 37.9, 30.6; HRMS (ESI): m/z calcd for: C26H23N2O, 379.1805 [M+H]+, found:
379.1822.
18. (a) Jiang, B.; Liu, Y.-P.; Tu, S.-J. Eur. J. Org. Chem. 2011, 3026; (b) Wang, S.-L.; Wu,
F.-Y.; Cheng, C.; Zhang, G.; Liu, Y.-P.; Jiang, B.; Shi, F.; Tu, S.-J. ACS Comb. Sci.
2011, 13, 135; (c) Jiang, B.; Cao, L.-J.; Tu, S.-J.; Zheng, W.-R.; Yu, H.-Z. J. Comb.
Chem. 2009, 11, 612; (d) Jiang, B.; Hao, W.-J.; Wang, X.; Shi, F.; Tu, S.-J. J. Comb.
Chem. 2009, 11, 846.
19. General procedure for the synthesis of polysubstituted fused pyrimidines 4
under microwave irradiation: In a 10-mL reaction vial, aromatic aldehyde 1
(2 mmol), tetrahydrothiopyran-4-one or trahydropyran-4-one 2 (1 mmol), t-
BuOK (2.0 mmol), t-BuOH (2.0 mL) were mixed and stirred at room temperature
for 10 min. Subsequently aryl amidine 3 (1.1 mmol) was added into the mixture
and then capped. The mixture was irradiated for a given time at 140 °C. Upon
completion as shown by TLC monitoring, the reaction mixture was cooled to
room temperature and neutralized by protonic acids and then diluted with cold
water. The solid product was filtered, washed with water and acetone, and
subsequently dried and then recrystallized from acetone to give the pure
20. The single-crystal growth was carried out in DMF at room temperature. X-ray
crystallographic analysis was performed with a Siemens SMART CCD and a Siemens
P4 diffractometer (graphite monochromator, Mo K
a radiation k = 0.71073). Crystal
data for 4s: C26H22N2O, crystal dimension 0.43 Â 0.21 Â 0.13 mm, Triclinic, space
ꢀ
group P1, a = 10.7052(14) Å, b = 13.4963(15) Å, c = 15.4034(16) Å,
a
= 71.4
730(10)°, b = 80.451(2)°,
c
= 75.7860(10)°, V = 2036.2(4) Å3, Mr = 378.46, Z = 4,
Dc = 1.235 g/cm3, k = 0.71073 Å,
R1 = 0.0898, wR2 = 0.1977.
l
(Mo
K
a
) = 0.076 mmÀ1
,
F(000) = 800,
product.
8-Benzyl-2,4-diphenyl-7,8-dihydro-5H-pyrano[4,3-d]pyrimidine