Synthesis of new unsymmetrical 4,5-dihydroxy-2-imidazolidinones. Dynamic NMR spectroscopic study of the prototropic tautomerism in 1-(2-benzimidazolyl)- 3-phenyl-4,5-dihydroxy-2-imidazolidinone

Article abstract of DOI:10.3390/11100768

The acid-catalyzed cyclocondensation in refluxing acetonitrile of aqueous glyoxal with N-heteroaryl-N′-phenylureas 4a-f (heteroaryl = 2-thiazolyl, 2-pyrimidinyl, 2-pyrazinyl, 2-pyridinyl, 3-pyridinyl and 2-benzimidazolyl) led to the formation of the corre

Full text of DOI:10.3390/11100768

Molecules 2006, 11, 768-775
molecules
ISSN 1420-3049
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Full Paper
Synthesis of New Unsymmetrical 4,5-Dihydroxy-2-
imidazolidinones. Dynamic NMR Spectroscopic Study of the
Prototropic Tautomerism in 1-(2-Benzimidazolyl)-3-phenyl-4,5-
dihydroxy-2-imidazolidinone
Mehdi Ghandi*, Abolfazl Olyaei and Farshid Salimi
School of Chemistry, University College of Science, University of Tehran, Tehran, Iran
* Author to whom correspondence should be addressed. E-mail: ghandi@khayam.ut.ac.ir; Tel.: (+98)-
21-61112250; Fax: (+98)-21-66495291
Received: 28 September 2006; in revised form: 11 October 2006 / Accepted: 12 October 2006 /
Published: 19 October 2006
Abstract: The acid-catalyzed cyclocondensation in refluxing acetonitrile of aqueous
glyoxal with N-heteroaryl-N'-phenylureas 4a-f (heteroaryl = 2-thiazolyl, 2-pyrimidinyl,
2-pyrazinyl, 2-pyridinyl, 3-pyridinyl and 2-benzimidazolyl) led to the formation of the
corresponding 1-heteroaryl-3-phenyl-4,5-dihydroxy-2-imidazolidinones 5a-f. All the
products were characterized by elemental and spectroscopic analyses. The free-energy
barrier (∆G≠) for prototropic tautomerism in 1-(2-benzimidazolyl)-3-phenyl-4,5-
dihydroxy-2-imidazolidinone (5f) was determined by dynamic NMR studies to be 81 ± 2
KJ mol-1.
Keywords: Dynamic NMR, N-Heteroaryl-N'-phenylurea, 2-Imidazolidinone, Glyoxal.
Introduction
Synthesis of imidazolidines through the cyclocondensation of diamines, bisamides and urea
derivatives with aqueous glyoxal and other appropriate carbonyl compounds has been the subject of
numerous investigations [1-10]. In 1962, Slezak et al. reported the acid-catalyzed reaction of urea
derivatives with aqueous glyoxal leading to the formation of the corresponding glycolurils 1 (Figure 1)
[11]. The formation of hydantoin derivatives 2 (Figure 1) had been found previously to take place

Molecules 2006, 11
769
under similar reaction conditions [12]. The additions of N,N'-dimethylurea and urea to aqueous glyoxal
under both acidic and basic conditions to form 4,5-dihydroxy-2-imidazolidinones derivatives 3 (Figure
1) have been studied by Vail et al. [13]. On the basis of NMR spectroscopy, they showed that initially
equimolar amounts of the cis and trans isomers were formed by a non-stereospecific addition, but the
resulting equilibrium product mixture contained predominantly the trans isomer. In acidic solution, the
products would be subject to protonation and subsequent formation of other products. 2-
Imidazolidinones are important building blocks in Medicinal Chemistry as central nervous system
depressants and enzyme inhibitors [14-16]. They are also used as textile finishing agents [17].
Figure 1. Structures of glycolurils 1, hydantoins 2 and 4,5-dihydroxy-2-imidazolidinones 3.
R
N
R
N
R
N
HO
OH
O
O
O
O
RN
NR
N
R
N
R
N
R
O
3
2
1
R = H, CH3
In the present work, we wish to report a facile and convenient synthetic route to some new
unsymmetrical 1,3-diarylsubstituted 4,5-dihydroxy-2-imidazolidinones 5a-f through the reaction of
aqueous glyoxal with N-heteroaryl-N'-phenylureas 4a-f in the presence of formic acid as catalyst. The
dynamic behavior of 1-(2-benzimidazolyl)-3-phenyl-4,5-dihydroxy-2-imidazolidinone (5f) was also
studied by variable temperature NMR.
Results and Discussion
N-Heteroaryl-N'-phenylureas 4a-f were prepared through the reaction of suitable primary
heteroarylamines (2-aminothiazole, 2-aminopyrimidine, 2-aminopyrazine, 2-aminopyridine, 3-amino-
pyridine and 2-aminobenzimidazole) with phenyl isocyanate [18-21]. In refluxing acetonitrile and in
the presence of formic acid as catalyst, treatment of compounds 4a-f with aqueous glyoxal afforded the
corresponding trans-1-heteroaryl-3-phenyl-4,5-dihydroxy-2-imidazolidinones 5a-f (Scheme 1). The
products 5a-f were purified by flash chromatography (FC) and characterized by spectroscopic
techniques. Yields, melting points, reaction times and elemental analyses are presented in Table 1.
The mass spectra of compounds 5a-f exhibited medium intensity parent ions, while the radical
cations of N-heteroaryl-N'-phenylureas 4a-f and heteroarylisocyanate cations appeared with high
intensity. The 1H-NMR spectra of compounds 5a-f showed two well-resolved AB quartet spin systems
corresponding to two chemically different CH-OH moieties. Based on the lack of coupling between
two unequivalent methine protons, it seems likely that the hydroxyl groups are trans to each other. The
other peaks of the spectra were those arising from the protons of two aromatic moieties. Upon addition
of D2O to the NMR samples, the hydroxyl signals disappeared and the signals of the methine moieties
quickly collapsed to two singlets.

Molecules 2006, 11
770
Scheme 1. Formic acid catalized reaction of N-heteroaryl-N'-phenylureas 4a-f with
aqueous glyoxal.
HO
OH
H
H
CH3CN
N
N
+ (CHO)2 aq
Ar
ph
N
N
HCOOH
ph
Ar
O
O
4a-f
a:
5a-f
N
N
S
Ar =
b:
c:
f:
N
N
N
N
N
N
e:
d:
N
H
Table 1. Yields, melting points and elemental analyses of compounds 5a-f.
Elemental Analysis (%)
Yield
Calcd. (Found)
Entry
Ar
Time/h Mp °C
%
70
90
80
85
75
C
H
N
S
51.98
3.97
15.16
5a
5b
5c
5d
5e
3
10
8
160-162
204-206
164-166
124-126
173-175
N
N
(51.76)
57.35
(4.02)
4.41
(14.96)
20.58
(57.17)
57.35
(4.45)
4.41
(20.43)
20.58
N
N
(57.23)
61.99
(4.38)
4.79
(20.51)
15.49
N
N
0.5
5
(61.78)
61.99
(4.90)
4.79
(15.38)
15.49
N
(61.94)
(4.83)
(15.42)
H
N
61.93
4.51
18.06
5f
4
226-228
65
(61.90)
(4.60)
(17.95)
N
Physicochemical data show that the NH proton in benzimidazoles, as in imidazoles, migrates
rapidly between the two nitrogen atoms (degenerate tautomerism) (Scheme 2). The imidazole ring with
a nonsymmetrical substitution exhibits an HN1…HN3 tautomerism that has been studied both
experimentally and theoretically [22].
1
The H-NMR spectrum of 5f in DMSO-d6 at room temperature (25 °C) exhibited two rather sharp
doublets at δ 7.48 and 7.50 ppm (J = 7.07 and 6.5 Hz), arising from CH-4' and CH-7' protons, each of
them exhibiting a further doublet splitting due to the long range coupling with one of the
benzimidazolyl hydrogens. Increasing the temperature results in coalescence of the two doublets (TC =
384 ± 1 K), as shown in Figure 2. Although no extensive line-shape analysis for 5f was undertaken, the
variable temperature spectra allowed us to calculate the free energy barriers ∆G ≠ for the dynamic

Molecules 2006, 11
771
NMR process in 5f from coalescence of the CH-4' and CH-7' protons. By using the expression, k =
π∆υ/ 2 , the first-order rate constant (k) for dynamic NMR effect in 5f was calculated as 31 s-1.
Scheme 2. Degenerate tautomerization of compound 5f.
H
2'
H
O
O
4'
7'
3'
5
2
OH
Ph
Ph
4
N
N
N
5'
6'
N
N
N
3
N
1
N
OH
1'
O
O
H
H
5f
Application of the absolute rate theory with a transmission coefficient of 1 gives the free energy of
activation (∆G ≠) as 81 ± 2 KJ mol-1 for compound 5f, where all known sources of errors are estimated
and included [23]. The experimental data available are not suitable for obtaining meaningful values of
∆H ≠ and ∆S ≠ even though the errors in ∆G ≠ are not large [24].
1
Figure 2. Variable-temperature 500 MHz H-NMR spectra of the aromatic region of 5f
in DMSO-d6.
Ph (Ho)
Ph (Hm) Ph (Hp)
H-5’, H-6’
H-4’, H-7’
OH
384
374
364
354
340
OH
OH
330
320
298 K
The 13C-NMR spectra of 5f also show 14 and 11 peaks at 298 and 384 K, respectively. This clearly
indicates that the tautomers are interconverting fast at 384 K on the NMR time scale. No conversion
occurred when we examined reaction of 4a-f with glyoxal in the presence of sodium hydroxide in
different solvents. On the other hand, reaction of compounds 5a-f with sodium hydroxide regenerated
the starting materials 4a-f. Imidazolidinones 5a-f are stable materials and can be stored at room
temperature for extended periods.
Conclusions
In summary, the reaction between N-heteroaryl-N'-phenylureas 4a-f with aqueous glyoxal in
acetonitrile under reflux conditions provides a simple one-pot entry into the synthesis of 1-heteroaryl-

Molecules 2006, 11
772
3-phenyl-4,5-dihydroxy-2-imidazilidinones 5a-f. Since scaling up of this easy method seems plausible,
utilization of the procedure in industrial applications such as the preparation of textile finishing agents
is conceivable. The free-energy barrier (∆G ≠) for prototropic tautomerism in 1-(2-benzimidazolyl)-3-
phenyl-4,5-dihydroxy-2-imidazolidinone (5f) was found to be 81 ± 2 KJ mol-1.
Experimental
General
All commercially available chemicals and reagents were used without further purification. Melting
points were determined with an Electrothermal model 9100 apparatus and are uncorrected. IR spectra
1
13
were recorded on a Shimadzu 4300 spectrophotometer. The H- and C-NMR spectra were recorded
in DMSO-d6 on a DRX-500 AVANCE spectrometer at 298 K. Chemical shifts (δ) are reported in ppm
and are referenced to the NMR solvent peak. Mass spectra of the products were obtained with a HP
(Agilent Technologies) 5937 Mass Selective Detector. Elemental analyses were carried out with a
Thermo Finnigan (FLASH 1112 SERIES EA) CHNS-O analyzer. Flash chromatography (FC) was
carried out using silica gel 60 (63-200 mesh). Progress of the reactions was monitored by TLC using
precoated sheets of silica gel Merck 60 F254 on aluminium.
General procedure for the synthesis of 1-heteroaryl-3-phenyl-4,5-dihydroxy-2-imidazolidinones 5a-f.
A stirring solution of N-heteroaryl-N'-phenylurea 4a-f (1 mmol), glyoxal (0.14 g of 40% aqueous
solution, 1 mmol) and formic acid (0.005 g of 98% aqueous solution, 0.1 mmol) in acetonitrile (30
mL) was refluxed for the time given in Table 1. The solvent was then removed under reduced pressure
and the crude material was purified by flash chromatography on silica gel, eluting with a 4:1
THF/hexane mixture to give a white crystalline product.
1-(2-Thiazolyl)-3-phenyl-4,5-dihydroxy-2-imidazolidinone (5a): Yield: 70%; m.p. 160-162 °C (from
acetonitrile); IR (KBr): 3323 (OH), 3058, 2943, 1730 (C=O), 1596, 1487, 1402, 1280, 1139 cm-1;
1H-NMR δ: 5.34 (d, 1H, J = 8.5 Hz, CH), 5.62 (d, 1H, J = 7.1 Hz, CH), 7.00 (d, 1H, J = 8.5 Hz, OH),
7.27 (d, 1H, J = 7.1 Hz, OH), 7.30 (d, 1H, J = 3.4 Hz, thiazole H-4), 7.50 (d, 1H, J = 3.4 Hz, thiazole
1
H-5), 7.19, 7.42 and 7.68 (3m, 5H, Ar-H); H-NMR (DMSO-d6 + D2O) δ: 5.33 (s, 1H, CH), 5.61 (s,
1H, CH), 7.26 (d, 1H, J = 3.4 Hz, thiazole H-4), 7.48 (d, 1H, J = 3.4 Hz, thiazole H-5), 7.18, 7.41 and
7.64 (3m, 5H, Ar-H); 13C-NMR δ: 84.18, 86.35, 114.58, 121.21, 125.23, 129.77, 138.41, 138.60,
152.72, 158.13 ppm; MS (EI): m/z 277 (M+); Anal. Calcd for C12H11N3O3S: C, 51.98; H, 3.97; N,
15.16. Found: C, 51.76; H, 4.02; N, 14.96.
1-(2-Pyrimidinyl)-3-phenyl-4,5-dihydroxy-2-imidazolidinone (5b): Yield: 90%; m.p. 204-206 °C (from
acetonitrile); IR (KBr): 3261 (OH), 3085, 2858, 1730 (C=O), 1569, 1456, 1380, 1299, 1060 cm-1;
1H-NMR δ: 5.22 (d, 1H, J = 7.9 Hz, CH), 5.68 (d, 1H, J = 6.3 Hz, CH), 6.82 (d, 1H, J = 6.3 Hz, OH),
6.84 (d, 1H, J = 7.9 Hz, OH), 7.22 (t, 1H, J = 4.8 Hz, pyrimidine H-5), 7.16 and 7.39-7.68 (2m, 5H,
Ar-H), 8.72 (d, 2H, J = 4.8 Hz, pyrimidine H-4, H-6); 1H-NMR (DMSO-d6 + D2O) δ: 5.22 (s, 1H, CH),

Molecules 2006, 11
773
5.67 (s, 1H, CH), 7.21 (t, 1H, J = 4.8 Hz, pyrimidine H-5), 7.17 and 7.38-7.63 (2m, 5H, Ar-H), 8.69 (d,
2H, J = 4.8 Hz, pyrimidine H-4, H-6); 13C-NMR δ: 63.83, 84.80, 117.43, 121.63, 124.92, 129.61,
139.17, 151.46, 157.88, 159.14 ppm; MS (EI): m/z 272 (M+); Anal. Calcd for C13H12N4O3: C, 57.35;
H, 4.41; N, 20.58. Found: C, 57.17; H, 4.45; N, 20.43.
1-(2-Pyrazinyl)-3-phenyl-4,5-dihydroxy-2-imidazolidinone (5c): Yield: 80%; m.p. 164-166 °C (from
1:1 THF-hexane); IR (KBr): 3400 (OH), 3066, 1708 (C=O), 1591, 1427, 1271, 1207, 1080
cm-1; 1H-NMR δ: 5.31 (d, 1H, J = 8.3 Hz, CH), 5.72 (d, 1H, J = 6.8 Hz, CH), 6.91 (d, 1H, J = 8.3 Hz,
OH), 6.93 (d, 1H, J = 6.8 Hz, OH), 7.17-7.69 (m, 5H, Ar-H), 8.37-9.45 (m, 3H, pyrazine H-3, H-5, H-
6); 1H-NMR (DMSO-d6 + D2O) δ: 5.30 (s, 1H, CH), 5.71 (s, 1H, CH), 7.18-7.65 (m, 5H, Ar-H), 8.35-
9.40 (m, 3H, pyrazine H-3, H-5, H-6); 13C-NMR δ: 82.52, 85.74, 121.69, 125.23, 129.70, 136.63,
138.67, 139.70, 143.03, 148.71, 153.17 ppm; MS (EI): m/z 272 (M+); Anal. Calcd for C13H12N4O3: C,
57.35; H, 4.41; N, 20.58. Found: C, 57.23; H, 4.38; N, 20.51.
1-(2-Pyridinyl)-3-phenyl-4,5-dihydroxy-2-imidazolidinone (5d): Yield: 85%; m.p. 124-126 °C (from
1:1 THF-hexane); IR (KBr): 3290 (OH), 3066, 2962, 1724 (C=O), 1595, 1483, 1311, 1176, 1047 cm-1;
1H-NMR δ: 5.25 (d, 1H, J = 8.0 Hz, CH), 5.80 (d, 1H, J = 6.4 Hz, CH), 6.71 (d, 1H, J = 6.4 Hz, OH),
1
6.83 (d, 1H, J = 8.0 Hz, OH), 7.11-8.39 (m, 9H, Ar-H); H-NMR (DMSO-d6 + D2O) δ: 5.24 (s, 1H,
13
CH), 5.79 (s, 1H, CH), 7.10-8.38 (m, 9H, Ar-H); C-NMR δ: 82.78, 85.14, 113.96, 119.63, 121.42,
124.83, 129.62, 138.86, 139.10, 148.55, 151.90, 153.53 ppm; MS (EI): m/z 271 (M+); Anal. Calcd for
C14H13N3O3: C, 61.99; H, 4.79; N 15.49. Found: C, 61.78; H, 4.90; N, 15.38.
1-(3-Pyridinyl)-3-phenyl-4,5-dihydroxy-2-imidazolidinone (5e): Yield: 75%; m.p. 173-175 °C (from
acetonitrile); IR (KBr): 3336 (OH), 3043, 2916, 1695 (C=O), 1581, 1490, 1413, 1271, 1070
cm-1; 1H-NMR δ: 5.29 (d, 1H, J = 8.3 Hz, CH), 5.34 (d, 1H, J = 8.1 Hz, CH), 6.88 (d, 1H, J = 8.3 Hz,
1
OH), 6.96 (d, 1H, J = 8.1 Hz, OH), 7.13-8.90 (m, 9H, Ar-H); H-NMR (DMSO-d6 + D2O) δ: 5.28 (s,
1H, CH), 5.33 (s, 1H, CH), 7.14-8.88 (m, 9H, Ar-H); 13C-NMR δ: 84.84, 85.61, 121.20, 124.42,
124.70, 127.69, 129.61, 136.08, 139.09, 142.15, 145.18, 153.84 ppm; MS (EI): m/z 271 (M+); Anal.
Calcd. for C14H13N3O3: C, 61.99; H, 4.79; N, 15.49. Found: C, 61.94; H, 4.83; N, 15.42.
1-(2-Benzimidazolyl)-3-phenyl-4,5-dihydroxy-2-imidazolidinone (5f): Yield: 65%; m.p. 226-228 °C
(from acetonitrile); IR (KBr): 3498, 3400, 3288, 3041, 2960, 1722 (C=O), 1627, 1568, 1498, 1460,
1271, 1147 cm-1; 1H-NMR δ: 5.35 (d, 1H, J = 8.5 Hz, CH), 5.65 (d, 1H, J = 6.9 Hz, CH), 7.02 (d, 1H, J
= 8.5 Hz, OH), 7.32 (d, 1H, J = 6.9 Hz, OH), 7.20, 7.44 and 7.72 (3m, 5H, Ar-H), 7.10 and 7.50 (2m,
1
4H, benzimidazole-H), 12.05 (s, 1H, NH); H-NMR (DMSO-d6 + D2O) δ: 5.35 (s, 1H, CH), 5.65 (s,
13
1H, CH), 7.21, 7.43 and 7.66 (3m, 5H, Ar-H), 7.12 and 7.49 (2m, 4H, benzimidazole-H); C-NMR
(298 K) δ: 83.61, 86.40, 112.25, 117.73, 121.41, 121.58, 122.03, 125.26, 129.78, 134.08, 138.52,
13
141.62, 146.36, 152.97; C NMR (384 K) δ: 84.16, 86.81, 112.55, 115.23, 121.80, 122.29, 125.44,
129.55, 138.74, 146.83, 153.42 ppm; MS (EI): m/z 310 (M+); Anal. Calcd for C16H14N4O3: C, 61.93;
H, 4.51; N, 18.06. Found: C, 61.90; H, 4.60; N, 17.95.

Molecules 2006, 11
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Acknowledgements
The authors wish to thank the Research Council of the University of Tehran for financial support.
References and Notes
1. Nematollahi, J.; Ketcham, R. Imidazoimidazoles. I. The reaction of ureas with glyoxal.
Tetrahydroimidazo[4,5-d]imidazole-2,5-diones. J. Org. Chem. 1963, 28, 2378-2380.
2. Vail, S. L.; Moran, C. M.; Moore, H. B.; Kullman, R. M. H. Amide-glyoxal reaction products. J.
Org. Chem. 1962, 27, 2071-2074.
3. Ghandi, M.; Salimi, F.; Olyaei, A. One-pot stereoselective synthesis of trans-4,5-dialkoxy-1,3-
bis(2-pyrimidinyl)imidazolidines through a three-component reaction. J. Heterocyclic Chem.
2006, 43, 791-794.
4. Katritzky, A. R.; Suzuki, K.; He, H.-Y. Convenient syntheses of unsymmetrical imidazolidines. J.
Org. Chem. 2002, 67, 3109-3114.
5. Larter, M. L.; Phillips, M.; Ortega, F.; Aguirre, G.; Somanathan, R.; Walsh, P. J. Synthesis of
racemic cis and trans 2,4,5-tripyridylimidazolines. Tetrahedron Lett. 1998, 39, 4785-4788.
6. Alexakis, A.; Tranchier, J.-P.; Lensen, N.; Mangeney, P. Monoaminals of glyoxal: Versatile
chirons. J. Am. Chem. Soc. 1995, 117, 10767-10768.
7. Gilbert, E. E. Tetramido derivatives of glyoxal. J. Chem. Eng. Data 1974, 19, 182-183.
8. Koppes, W. M.; Chaykovsky, M.; Adolph, H. G.; Gilardi, R.; George, C. Synthesis and structure
of some peri-substituted 2,4,6,8-tetraazabicyclo[3.3.0]octanes. J. Org. Chem. 1987, 52, 1113-
1119.
9. Frick, J. G. Jr.; Harper, R. J. Jr. Reaction of dimethylurea and glyoxal. Ind. Eng. Chem. Prod. Res.
Dev. 1982, 21, 599-600.
10. Ghandi, M.; Olyaei, A.; Salimi, F. Four-component cyclocondensation of aminodiazines, glyoxal,
formaldehyde and methanol to imidazolidines. Synth. Commun. 2006, 37, in press.
11. Slezak, F. B.; Bluestone, H.; Magee, T. A.; Wotiz, J. H. Preparation of substituted glycolurils and
their N-chlorinated derivatives. J. Org. Chem. 1962, 27, 2181-1283.
12. Dunnavant, W. R.; James, F. L. Molecular rearrangements. I. The base-catalyzed condensation of
benzil with urea. J. Am. Chem. Soc. 1956, 78, 2740-2743.
13. Vail, S. L.; Barker, R. H.; Mennitt, P. G. Formation and identification of cis- and trans-
dihydroxyimidazolidinones from ureas and glyoxal. J. Org. Chem. 1965, 30, 2179-2182.
14. Wright, W. B., Jr.; Brabander, H. J.; Hardy, R. A., Jr.; Osterberg, A. C. Central nervous system
depressant. I. 1-Aminoalkyl-3-aryl derivatives of 2-imidazolidinone,1a-c 2-imidazolidinethione and
tetrahydro-2(1H)-pyrimidinone1d. J. Med. Chem. 1966, 9, 852-857.
15. Lien, E. J.; Hussain, M.; Golden. M. P. Structure-activity correlations for the central nervous
system depressant 2-imidazolidinones. J. Med. Chem. 1970, 13, 623-626.
16. Smissman, E. E.; Inloes, R. L.; El-Antably, S.; Shaffer, P. J. Specificity in enzyme inhibition. 3.
Synthesis of 5-substituted 2,2-dimethyl-4-imidazolidinones as inhibitors of tyrosine
decarboxylase and histidine decarboxylase. J. Med. Chem. 1976, 19, 161-163.

Molecules 2006, 11
775
17. Beachem, M. T. Novel imidazolidinones and their use as textile finishing agents. U.S. Patent
3,260,565, 1966.
18. Dyre, E.; Gluntz, M. L.; Tanck, E. J. Carbamates and ureas derived from amino- and oxo-
pyrimidines. J. Org. Chem. 1962, 27, 982-985.
19. Browne, E. J.; Polya, J. B. Preparation of amides derived from heterocyclic amines. J. Chem. Soc.
C 1968, 2904-2908.
20. Novikov, E. G.; Tugarinova, I. N. The reaction of 3- and 4-aminopyridines with isocyanates and
isothiocyanates. Khim. Geterotsikl. Soedin. 1968, 281-283.
21. Kaufmann, H. P.; Schulz, P. IX. Benzothiazolylureas. Arch. Pharm. 1935, 273, 31-52.
22. For reviews, see, e.g.: (a) Grimmett, M. R. In Comprehensive Heterocyclic Chemistry II;
Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V.; Eds.; Pergamon Press: Oxford, U. K. 1996; Vol.
3, p. 77. (b) Rauhut, G. In Advances in Heterocyclic Chemistry; Katritzky, A. R.; Ed.; Academic
Press: San Diego, CA 2001; Vol. 81, p. 1.
23. Gunther, H. NMR Spectroscopy, 2nd ed.; Wiley: New York, 1995; Chapter 9.
24. Anet, F. A. L.; Anet, R. In Dynamic Nuclear Magnetic Resonance Spectroscopy; Cotton, F. A.;
Jackman, L. M., Eds.; Academic: New York, 1975; pp. 543-619.
Sample Availability: Samples of compounds 5a-f are available from the authors.
© 2006 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.