A simple three-component condensation: highly efficient microwave-assisted one-pot synthesis of polyfunctioned pyridine derivatives

Article abstract of DOI:10.1002/jhet.19

A simple facile one-step microwave-enhanced synthesis of methyl 4-substituted-6-amino-5-cyano-2-methylpyridine-3-carboxylate derivatives via a three-component reaction of aromatic aldehydes, malono-nitrile, and methyl 3-aminobut-2-enoate has been develope

Full text of DOI:10.1002/jhet.19

54
A Simple Three-Component Condensation: Highly Efficient
Microwave-Assisted One-Pot Synthesis of Polyfunctional
Pyridine Derivatives
Vol 46
Shujiang Tu,* Dianxiang Zhou, Longji Cao, Chunmei Li, and Qingqing Shao
School of Chemistry and Chemical Engineering, Xuzhou Normal University, Key Laboratory of
Biotechnology for Medicinal Plant, Xuzhou, Jiangsu 221116, People’s Republic of China
*E-mail: laotu@xznu.edu.cn
Received July 1, 2008
DOI 10.1002/jhet.19
Published online 6 February 2009 in Wiley InterScience (www.interscience.wiley.com).
A simple facile one-step microwave-enhanced synthesis of methyl 4-substituted-6-amino-5-cyano-2-
methylpyridine-3-carboxylate derivatives via a three-component reaction of aromatic aldehydes, malono-
nitrile, and methyl 3-aminobut-2-enoate has been developed. It is an efficient and promising synthetic
strategy to build the polyfunctional pyridine skeleton.
J. Heterocyclic Chem., 46, 54 (2009).
INTRODUCTION
As part of an ongoing development of efficient proto-
cols for the preparation of polysubstituted heterocycles
from common intermediates [15], we recently discov-
ered a simple and efficient method for the synthesis of
polysubstituted pyridines (Scheme 1) via aldehydes,
malononitrile, and methyl 3-aminobut-2-enoate under
microwave (MW) irradiation.
Multicomponent reactions (MCRs), an important class
of organic reactions, are one-pot processes with at least
three components to form a single product, which incor-
porates most or even all of the starting materials [1].
The huge interest for such multicomponent reactions
during the last years has been oriented toward develop-
ing combinatorial chemistry procedures, because of their
high efficiency and convenience of these reactions in
comparison with multistage procedures. Hence, much
scientific effort has been focused on the development of
multicomponent procedures to prepare diverse heterocy-
clic compound libraries [2].
RESULTS AND DISCUSSION
To optimize the reaction conditions, different organic
solvents, such as ethanol, glycol, acetic acid, DMF, and
mixed glycol-HOAc were tested in the synthesis of 4b
at 100ꢀC. Table 1 show that the reactions in mixed gly-
col-HOAc (2:1, v/v) gave the best results (entry 6 of
Table 1).
Pyridine and its derivatives have a vast range of bio-
logical activities. They have been used as herbicides [3],
for enrichment of cereals [4], for regulation of arterial
pressure [5], and cholesterol levels in blood [6]. In addi-
tion, some pyridines constitute an important class of
antitumor compounds, which have been attracting signif-
icant attention [7,8]. Some polyfunctional pyridines are
used as nonlinear optical materials [9], electrical materi-
als [10], chelating agents in metal-ligand chemistry [11],
and as fluorescent liquid crystals [12]. Therefore, devel-
opment of efficient procedures toward functionalized
pyridines is a quite important task in organic synthesis
[13].
Moreover, to further optimize the reaction tempera-
ture, reactions using 4-chlorobenzaldehyde (1b, 1.0
mmol), malononitrile (2, 1.0 mmol), and methyl 3-ami-
nobut-2-enoate (3, 1.0 mmol) were carried out in the
range of 90–150ꢀC in increments of 10ꢀC each time in
mixed glycol-HOAc (2:1, v/v) under microwave irradia-
tion (initial power 100 W, maximum power 200 W).
The results are shown in Table 2. When the temperature
was increased from 90 to 120ꢀC, the yield of product 4b
was improved. However, no significant increase in the
There is a great variety of methods described in the
literature to synthesize similar skeleton [14]. Many prec-
edent methods, however, have inevitable drawbacks: the
aromatized polysubstituted pyridines were previously
mostly synthesized through two steps: 1,4-DHPs were
first prepared, which further proceeded to be oxidized to
provide the corresponding aromatized compounds.
Scheme 1
C
V
2009 HeteroCorporation

January 2009
A Simple Three-Component Condensation: Highly Efficient Microwave-Assisted
One-Pot Synthesis of Polyfunctional Pyridine Derivatives
55
Table 1
Solvent optimization for the synthesis of 4b under MW.
Table 2
Temperature optimization for the synthesis of 4b under MW.
Entry
Solvent
Time (min)
Yield (%)
Entry
T (ꢀC)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
EtOH
glycol
HOAc
12
10
10
10
9
37
54
55
48
60
76
70
64
1
2
3
4
5
6
7
90
100
110
120
130
140
150
9
9
9
7
7
7
7
70
76
83
88
85
83
80
DMF
glycol-HOAc(1:1)a
glycol-HOAc(2:1)a
glycol-HOAc(3:1)a
glycol-HOAc(4:1)a
9
9
9
a
Volume ratio.
the aromatized product 4. This type of hydrogen loss
was well precedented [16].
To test the mechanism described earlier, the reaction
of intermediate product 5c and methyl 3-aminobut-2-
enoate 3 was carried out under microwave irradiation
conditions. The target compound 4c was obtained, in
similar yields by the one-pot reaction. The results sup-
ported the proposed mechanism (Scheme 3).
yield of product 4b was observed as the reaction tem-
perature was raised from 130 to 150ꢀC. Therefore, the
temperature of 120ꢀC was chosen for all further MW-
assisted reactions.
The use of these optimal microwave experimental
conditions [120ꢀC, glycol-HOAc (2:1)] for the reactions
of different aromatic aldehydes afforded good yields of
polysubstituted pyridine derivatives. The results (Table
3, entries 1–10) indicated that aromatic aldehydes bear-
ing either electron-donating (such as alkoxyl groups) or
electron-withdrawing (such as nitro or halide groups)
functional groups were all suitable for the reaction.
Moreover, a heterocyclic aldehyde, thiophene-2-carbal-
dehyde (Table 3, entry 11), still showed high reactivity
under these standard conditions.
In this study, all the products were characterized by
1
IR and H NMR spectral data as well as elemental anal-
yses. Furthermore, the structure of 4a [17] was estab-
lished by X-ray crystallographic analysis. The molecular
structure of 4a was shown in Figure 1.
In conclusion, the microwave-assisted synthesis of
polysubstituted pyridines in this paper is an efficient
methodology allowing the facile preparation of these
important polycyclic compounds. This procedure offers
several advantages including operational simplicity,
increased safety for small-scale high-speed synthesis
that makes it a useful and attractive process for the syn-
thesis of these compounds.
Although the detailed mechanism of the above reac-
tion remains to be fully clarified, the formation of 4
could be explained by a possible reaction sequence pre-
sented in Scheme 2. Compound 4 is expected to proceed
via initial condensation of aromatic aldehydes with
malononitrile to afford alkylidenemalononitrile 5, which
further undergoes in situ Michael addition with methyl
3-aminobut-2-enoate 3, to yield intermediate 7, which is
then cyclized and subsequently dehydrogenated to afford
EXPERIMENTAL
Microwave irradiation was carried out with a microwave
oven EmrysTM Creator from Personal Chemistry, Uppsala,
Table 3
Synthesis of products 4 under MW.
Entry
Product
Ar
Time (min)
Yield (%)
Mp (ꢀC)
1
4a
4b
4c
4d
4e
4f
4g
4h
4i
4-FC6H4
4-ClC6H4
4-BrC6H4
4-NO2C6H4
4-CH3C6H4
2-ClC6H4
6
7
89
88
89
87
88
85
86
88
84
83
82
279–281
254–256
248–250
280–282
295–297
268–270
256–258
252–254
230–232
263–265
274–276
2
3
4
6
6
5
6
9
7
7
8
C6H5
6
8
3,4-Cl2C6H3
2,3-(CH3O)2C6H3
3,4-(OCH2O)C6H3
thiophen-2-yl
9
10
9
8
10
11
4j
4k
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

56
S. Tu, D. Zhou, L. Cao, C. Li, and Q. Shao
Vol 46
Scheme 2
Figure 1. ORTEP diagram of 4a.
Sweden. Melting points were determined in the open capilla-
ries and were uncorrected. IR spectra were taken on a FTIR-
Tensor 27 spectrometer in KBr pellets and reported in cmꢁ1
.
1H NMR spectra were measured on a Bruker DPX 400 MHz
spectrometer using TMS as an internal standard and DMSO-d6
as solvent. Elemental analysis was determined by using a
Perkin–Elmer 240c elemental analysis instrument. X-Ray crys-
tallographic analysis was performed with a Siemens SMART
CCD and a Siemens P4 diffractometer.
ing to the above general procedure, this compound is known
(RN: 176689-71-7) [14d]; ir (potassium bromide): 3383, 3324,
3178, 3086, 2221, 1721, 1653, 1576, 1496, 1378, 1284, 1197,
1
1094, 960, 863, 661 cmꢁ1; H NMR: 7.57 (d, 2H, J ¼ 8.4 Hz,
20,40-ArH), 7.40 (s, 2H, NH2), 7.34 (d, 2H, J ¼ 8.4 Hz, 30,50-
ArH), 3.44 (s, 3H, OCH3), 2.39 (s, 3H, CH3). Anal. calcd for
C15H12ClN3O2: C, 59.71; H, 4.01; N, 13.93. Found: C, 59.76;
H, 4.05; N, 13.90.
General procedure for the one-pot synthesis of com-
pounds 4 under microwave irradiation conditions. Typically,
in a 10-mL EmrysTM reaction vial, aldehyde 1 (1 mmol),
malononitrile 2 (1 mmol, 0.066 g), methyl 3-aminobut-2-
enoate 3 (1 mmol, 0.115 g), glycol (1.0 mL), and HOAc (0.5
mL) were mixed and then capped. The mixture was irradiated
for a given time at 120ꢀC under microwave irradiation (initial
power 100 W and maximum power 200 W). Upon completion,
monitored by TLC, the reaction mixture was cooled to room
temperature and then poured into cold water. The solid product
was collected by Bu¨chner filtration and was further purified by
recrystallization from EtOH (95%) to give the pure product.
Methyl 6-amino-5-cyano-4-(4-fluorophenyl)-2-methyl-pyri-
dine-3-carboxylate (4a). This compound was obtained accord-
ing to the above general procedure; ir (potassium bromide):
3390, 3321, 3172, 3076, 2220, 1715, 1652, 1565, 1434, 1376,
Methyl 6-amino-4-(4-bromophenyl)-5-cyano-2-methyl-pyri-
dine-3-carboxylate (4c). This compound was obtained accord-
ing to the above general procedure; ir (potassium bromide):
3405, 3313, 3161, 3069, 2217, 1718, 1651, 1557, 1437, 1376,
1
1283, 1104, 1012, 957, 882, 665 cmꢁ1; H NMR: 7.71 (d, 2H,
J ¼ 8.4 Hz, 30,50-ArH), 7.40 (s, 2H, NH2), 7.27 (d, 2H, J ¼
8.4 Hz, 20,40-ArH), 3.45 (s, 3H, OCH3), 2.39 (s, 3H, CH3).
Anal. calcd for C15H12BrN3O2: C, 52.04; H, 3.49; N, 12.14.
Found: C, 52.00; H, 3.45; N, 12.15.
Methyl 6-amino-5-cyano-2-methyl-4-(4-nitrophenyl)-pyri-
dine-3-carboxylate (4d). This compound was obtained accord-
ing to the above general procedure; ir (potassium bromide):
3383, 3331, 3151, 3061, 2222, 1720, 1661, 1562, 1433, 1382,
1
1282, 1107, 1017, 955, 888, 665 cmꢁ1; H NMR: 8.35 (d, 2H,
1229, 1166, 1077, 958, 882, 665 cmꢁ1 1H NMR: 7.39–7.37
;
J ¼ 8.8 Hz, 30,50-ArH), 7.62 (d, 2H, J ¼ 8.4 Hz, 20,40-ArH),
7.53 (s, 2H, NH2), 3.40 (s, 3H, OCH3), 2.43 (s, 3H, CH3).
Anal. calcd for C15H12N4O4: C, 57.69; H, 3.87; N, 17.94.
Found: C, 57.70; H, 3.85; N, 17.95.
(m, 2H, 30,50-ArH), 7.36 (s, 2H, NH2), 7.34–7.31 (m, 2H,
20,40-ArH), 3.43 (s, 3H, OCH3), 2.38 (s, 3H, CH3). Anal. calcd
for C15H12FN3O2: C, 63.15; H, 4.24; N, 14.73. Found: C,
63.12; H, 4.28; N, 14.75.
Methyl 6-amino-5-cyano-2-methyl-4-p-tolylpyridine-3-car-
boxylate (4e). This compound was obtained according to the
above general procedure; ir (potassium bromide): 3338, 3321,
3173, 3048, 2219, 1712, 1652, 1560, 1434, 1376, 1286, 1110,
Methyl 6-amino-4-(4-chlorophenyl)-5-cyano-2-methyl-pyri-
dine-3-carboxylate (4b). This compound was obtained accord-
1
1077, 961, 882, 664 cmꢁ1; H NMR: 7.30 (d, 2H, J ¼ 7.6 Hz,
Scheme 3
20,40-ArH), 7.19 (d, 2H, J ¼ 8.0 Hz, 30,50-ArH), 7.11 (s, 2H,
NH2), 3.43 (s, 3H, OCH3), 2.37 (s, 6H, CH3). Anal. calcd for
C16H15N3O2: C, 68.31; H, 5.37; N, 14.94. Found: C, 68.35; H,
5.39; N, 14.95.
Methyl 6-amino-4-(2-chlorophenyl)-5-cyano-2-methyl-pyri-
dine-3-carboxylate (4f). This compound was obtained accord-
ing to the above general procedure; ir (potassium bromide):
3385, 3325, 3177, 3052, 2222, 1717, 1654, 1594, 1431, 1378,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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A Simple Three-Component Condensation: Highly Efficient Microwave-Assisted
One-Pot Synthesis of Polyfunctional Pyridine Derivatives
57
1283, 1168, 1035, 958, 802, 663 cmꢁ1 1H NMR: 7.61–7.59
;
REFERENCES AND NOTES
(m, 1H, ArH), 7.49 (s, 2H, NH2), 7.47–7.42 (m, 2H, ArH),
7.29–7.27 (m, 1H, ArH), 3.37 (s, 3H, OCH3), 2.45 (s, 3H,
CH3). Anal. calcd for C15H12ClN3O2: C, 59.71; H, 4.01; N,
13.93. Found: C, 59.75; H, 4.04; N, 13.95.
[1] (a) Hulme, C.; Gore, V. Curr Med Chem 2003, 10, 51; (b)
Domling, A.; Ugi, I. Angew Chem Int Ed Engl 2000, 39, 3168; (c)
Nair, V.; Rajesh, C.; Vinod, A. U.; Bindu, S.; Sreekanth, A. R.;
Mathen, J. S.; Balagopal, L. Acc Chem Res 2003, 36, 899; (d) Zhu, J.
Eur J Org Chem 2003, 7, 1133; (e) Domling, A. Curr Opin Chem Biol
2002, 6, 306.
Methyl 6-amino-5-cyano-2-methyl-4-phenylpyridine-3-car-
boxylate (4g). This compound was obtained according to the
above general procedure, this compound is known (RN:
176689-69-3) [14d]; ir (potassium bromide): 3395, 3320, 3169,
3057, 2219, 1714, 1652, 1558, 1436, 1377, 1284, 1168, 1077,
[2] Orru, R. V. A.; de Greef, M. Synthesis 2003, 1471.
[3] Temple, C. J.; Rener, G. A.; Waud, W. R.; Noker, P. E. J
Med Chem 1992, 35, 3686.
1
960, 803, 662 cmꢁ1; H NMR: 7.50–7.48 (m, 3H, ArH), 7.35
[4] Badgett, C. O.; Woodward, C. F. J Am Chem Soc 1947,
69, 2907.
(s, 2H, NH2), 7.31–7.29 (m, 2H, ArH), 3.39 (s, 3H, OCH3),
2.39 (s, 3H, CH3). Anal. calcd for C15H13N3O2: C, 67.40; H,
4.90; N, 15.72; Found: C, 67.44; H, 4.95; N, 15.70.
[5] Mercier, J.; Gavend, M.; VanLuv, V.; Dessaigne, S. Congr
Union-Ther Int [CR] 1963, 8, 361.
Methyl 6-amino-4-(3,4-dichlorophenyl)-5-cyano-2-methyl-
pyridine-3-carboxylate (4h). This compound was obtained
according to the above general procedure; ir (potassium bro-
mide): 3395, 3315, 3168, 3066, 2216, 1712, 1650, 1505, 1449,
[6] Dorner, G.; Fischer, F. W. Arezenmittel Forsch 1961, 11,
110.
[7] Boger, D. L.; Nakahara, S. J Org Chem 1991, 56, 880.
[8] (a) Boger, D. L.; Kasper, A. M. J Am Chem Soc 1989,
111, 1517; (b) Zhang, T. Y.; Stout, J. R.; Keay, J. G.; Scriven, E. F.
V.; Toomey, J. E.; Goe, G. L. Tetrahedron 1995, 51, 13177.
[9] Wang, H.; Helgeson, R.; Ma, B.; Wudl, F. J Org Chem
2000, 65, 5862.
1377, 1287, 1167, 1038, 926, 820, 775 cmꢁ1 1H NMR: 7.78
;
(d, 1H, J ¼ 8.4 Hz, ArH), 7.68–7.67 (m, 1H, ArH), 7.47 (s,
2H, NH2), 7.32 (dd, 1H, J1 ¼ 8.0 Hz, J2 ¼ 2.4 Hz, ArH), 3.47
(s, 3H, OCH3), 2.41 (s, 3H, CH3). Anal. calcd for
C15H11Cl2N3O2: C, 53.59; H, 3.30; N, 12.50. Found: C, 53.60;
H, 3.33; N, 12.55.
[10] Kanbara, T.; Kushida, T.; Saito, N.; Kuwajima, I.; Kubota,
K.; Yamamoto, T. Chem Lett 1992, 583.
[11] Meyer, T. J. Acc Chem Res 1989, 22, 163.
Methyl 6-amino-5-cyano-4-(2,3-dimethoxyphenyl)-2-meth-
ylpyridine-3-carboxylate (4i). This compound was obtained
according to the above general procedure; ir (potassium bro-
mide): 3384, 3331, 3177, 3050, 2224, 1713, 1657, 1567, 1433,
[12] Harada, H.; Watanuki, S.; Takuwa, T.; Kawaguchi, K.;
Okazaki, T.; Hirano, Y.; Saitoh, C. PCT Int. Appl. WO 2002,006,237
Al (2002); p 92.
[13] (a) Pavluchenko, A. I.; Petrov, V. F.; Smirnova, N. I. Liq
Cryst 1995, 19, 811; (b) Yates, F.; Courts, R. T.; Casy, A. F. In Pyri-
dine and Its Derivatives: Supplement IV; Abramovitch, R. A., Ed.;
Wiley: New York, 1975; p 445.
1
1335, 1265, 1193, 1091, 818, 743 cmꢁ1; H NMR: 7.31 (s, 2H,
NH2), 7.15–7.09 (m, 2H, ArH), 6.64 (dd, 1H, J1 ¼ 8.0 Hz, J2 ¼
2.4 Hz, ArH), 3.86 (s, 3H, OCH3), 3.61 (s, 3H, OCH3), 3.41 (s,
3H, OCH3), 2.40 (s, 3H, CH3). Anal. calcd for C17H17N3O4: C,
62.38; H, 5.23; N, 12.84. Found: C, 62.36; H, 5.25; N, 12.80.
[14] (a) Hantzsch, A. Justus Liebigs Ann Chem 1882, 215, 72;
(b) Janis, R. A.; Silver, P. J.; Triggle, D. J Adv Drug Res 1987, 16,
309; (c) Pfister, J. R. Synthesis 1990, 689; (d) Urbahns, K.; Goldmann,
S.; Heine, H.-G; Junge, B.; Schohe-Loop, R.; Sommermeyer, H.;
Glaser, T.; Wittka, R.; De Vry, J. (Bayer A.-G., Germany). Ger. Offen.
AN 1996:303721 (1996); 20 p; (e) Marco, J. L.; de los Rios, C.;
Garcia, A. G.; Villarroya, M.; Carreiras, M. C.; Martins, C. Bioorg
Med Chem 2004, 12, 2199.
Methyl
6-amino-4-(benzo[d][1,3]dioxol-6-yl)-5-cyano-2-
methylpyridine-3-carboxylate (4j). This compound was
obtained according to the above general procedure; ir (potas-
sium bromide): 3380, 3325, 3171, 3052, 2225, 1712, 1658,
;
1567, 1430, 1338, 1264, 1183, 1090, 810, 750 cmꢁ1 1H
NMR: 7.27 (s, 2H, NH2), 7.02 (d, 1H, J ¼ 8.0 Hz, ArH),
6.92–6.91 (m, 1H, ArH), 6.75 (dd, 1H, J1 ¼ 8.0 Hz, J2 ¼ 1.6
Hz, ArH), 6.12 (s, 2H, CH2), 3.48 (s, 3H, OCH3), 2.35 (s, 3H,
CH3). Anal. calcd for C16H13N3O4: C, 61.73; H, 4.21; N,
13.50. Found: C, 61.76; H, 4.25; N, 13.54.
[15] (a) Tu, S.-J.; Jiang, B.; Zhang, Y.; Zhang, J.-Y.; Jia,
R.-H. Chem Lett 2006, 12, 1338; (b) Tu, S.-J.; Jiang, B.; Zhang,
J.-Y.; Zhang, Y.; Jia, R.-H.; Li, C.-M.; Zhou, D.-X.; Cao, L.-J.; Shao,
Q.-Q. Synlett 2007, 3, 480; (c) Tu, S.-J.; Jiang, B.; Zhang, Y.; Jia,
R.-H.; Zhang, J.-Y.; Yao, C.-S.; Shi, F. Org Biomol Chem 2007, 5,
355.
Methyl 6-amino-5-cyano-2-methyl-4-(thiophen-2-yl)pyrid-
ine-3-carboxylate (4k). This compound was obtained according
to the above general procedure; ir (potassium bromide): 3390,
3320, 3163, 3060, 2219, 1713, 1654, 1560, 1434, 1330, 1261,
[16] (a) Yoneda, F.; Yano, T.; Higuchi, M.; Koshiro, A. Chem
Lett 1979, 155; (b) Devi, I.; Kumarb, B. S. D.; Bhuyana, P. J. Tetrahe-
dron Lett 2003, 44, 8307; (c) Evdokimov, N. M.; Magedov, I. V.;
Kireev, A. S.; Kornienko, A. Org Lett 2006, 8, 899.
1
1168, 1041, 839, 736 cmꢁ1; H NMR: 7.81 (dd, 1H, J1 ¼ 8.0
Hz, J2 ¼ 1.2 Hz, ArH), 7.35 (s, 2H, NH2), 7.29–7.28 (m, 1H,
ArH), 7.21–7.19 (m, 1H, ArH), 3.55 (s, 3H, OCH3), 2.35 (s,
3H, CH3). Anal. calcd for C13H11N3O2S: C, 57.13; H, 4.06; N,
15.37; S, 11.73. Found: C, 57.16; H, 4.05; N, 15.34; S, 11.75.
[17] The single-crystal growth was carried out in ethanol at
room temperature. X-ray crystallographic analysis was performed with
a Siemens SMART CCD and a Semens P4 diffractometer (graphite
˚
monochromator, MoKa radiation k ¼ 0.71073 A). Crystal data for 4a:
Empirical formula C15H12FN3O2, colorless, crystal dimensions 0.38 ꢂ
Acknowledgments. The authors are grateful for financial
support from the National Science Foundation of China (No.
20672090) and Natural Science Foundation of the Jiangsu
Province (No. BK2006033), Six Kinds of Professional Elite
Foundation of the Jiangsu Province (No. 06-A-039).
˚
0.10 ꢂ 0.07 mm, triclinic, space group p-1, a ¼ 6.549(5) A, b ¼
ꢀ
ꢀ
˚
˚
7.658(5) A, c ¼ 14.093(10) A, a ¼ 81.691(11) , b ¼ 86.585(11) ,
3
ꢀ
˚
c ¼ 84.035(10) , V ¼ 694.8(8) A , Mr ¼ 285.28, Z ¼ 2, Dc ¼ 1.364
Mg/m3 , k ¼ 0.71073 A, l (MoKa) ¼ 0.102 mmꢁ1, F(000) ¼ 296,
˚
S ¼ 0.937, R1 ¼ 0.0655, wR2 ¼ 0.1296.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet