Liquid-phase organic synthesis of thiazoles using poly(ethylene glycol)-bound sulfonyl chloride resin

Article abstract of DOI:10.1080/00397910802136672

Reaction of poly(ethylene glycol) (PEG)-bound sulfonic acid with thionyl chloride formed difunctionalized PEG-bound sulfonyl chloride, which was treated with α-hydroxyketones, followed by treatment with thioamides in the presence of potassium carbonate, to afford thiazoles in good yields with a facile workup procedure. Copyright Taylor & Francis Group, LLC.

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Liquid-Phase Organic
Synthesis of Thiazoles Using
Poly(ethylene glycol)–Bound
Sulfonyl Chloride Resin
a
a
a
Xiao-Ling Liu , Qiu-Ying Wang , Shou-Ri Sheng
,
a
a
Chen Xu & Ming-Zhong Cai
a
College of Chemistry and Chemical Engineering,
Jiangxi, Normal University (Yaohu Campus) ,
Nanchang, China
Published online: 12 Sep 2008.
To cite this article: Xiao-Ling Liu , Qiu-Ying Wang , Shou-Ri Sheng , Chen Xu & Ming-
Zhong Cai (2008) Liquid-Phase Organic Synthesis of Thiazoles Using Poly(ethylene
glycol)–Bound Sulfonyl Chloride Resin, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 38:19, 3338-3345,
DOI: 10.1080/00397910802136672
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1
Synthetic Communications , 38: 3338–3345, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802136672
Liquid-Phase Organic Synthesis of Thiazoles
Using Poly(ethylene glycol)–Bound Sulfonyl
Chloride Resin
Xiao-Ling Liu, Qiu-Ying Wang, Shou-Ri Sheng, Chen Xu,
and Ming-Zhong Cai
College of Chemistry and Chemical Engineering, Jiangxi
Normal University (Yaohu Campus), Nanchang, China
Abstract: Reaction of poly(ethylene glycol) (PEG)–bound sulfonic acid with
thionyl chloride formed difunctionalized PEG-bound sulfonyl chloride, which
was treated with a-hydroxyketones, followed by treatment with thioamides in
the presence of potassium carbonate, to afford thiazoles in good yields with a
facile workup procedure.
Keywords: Liquid-phase organic synthesis, PEG-bound sulfonyl chloride,
thiazole
In recent years, design and synthesis of pharmacologically relevant
heterocyclic molecules by combinatorial techniques have the
[1]
attention of medicinal chemists. The use of soluble polymer support
[
2]
in combinatorial synthetic methodologies facilitates library synthesis
3]
[
and overcomes the difficulty of solid-phase reactions. Soluble polymer–
supported reactions are easily monitored using routine analytical techni-
1
ques such as thin-layer chromatography (TLC), IR, and H NMR.
[4]
Thiazoles are a class of important heterocycles that have attracted con-
siderable attention because of their biological properties. For example,
[
they are known to be ligands of estrogen receptors, as well as a
5]
[
6]
novel class of adenosine receptors antagonists. Some thiazole deriva-
tives have found application in the development and preparation of
antibiotic or anti-inflammatory drugs. Other analogs are broadly used as
Received January 31, 2008.
Address correspondence to Shou-Ri Sheng, College of Chemistry and Chemical
Engineering, Jiangxi Normal University (Yaohu Campus), Nanchang, 330022,
China. E-mail: shengsr@jxnu.edu.cn
3
338

Thiazole Synthesis Using Sulfonyl Chloride Resin
3339
fungicides, inhibiting in vivo the growth of Xanthomonas, as an ingredient
[
7]
of herbicides, or as schistosomicidal and anthelmintic drugs. Therefore,
many synthetic methods for thiazole rings are well documented.
Among these methods, the use of solid-phase organic synthesis (SPOS)
methodology for the thiazole derivatives has also been investigated
[
8]
widely. However, to our knowledge, a synthetic route to the thiazoles
on soluble polymer supports has not been reported. Based on our
previous study on the use of PEG-bound sulfonic acid for the preparation
[
9]
of 1,1-diacetates, we report herein an efficient liquid-phase organic syn-
thesis (LOPS) of thiazoles with PEG-bound sulfonyl chloride (Scheme 1).
The synthesis of a sulfonyl chloride linker on PEG polymer (average
mass 4000) first was investigated. As previously reported, the dimesyla-
tion from PEG 4000 with methanesulfonyl chloride was carried out and
[
10a]
then converted to the corresponding dibromide resin,
further treated with 4-hydroxybenzenesulfonic acid and sodium
which was
[
10b]
hydroxide,
followed by treatment with concentrated HCl to form
[
9]
the difunctionalized PEG-supported sulfonic acid 1. Then reaction of
PEG-supported sulfonic acid 1with thionyl chloride in N,N-dimethyl-
formamide gave the difunctionalized PEG–sulfonyl chloride resin 2 in
7
8% overall yield, and all steps were readily monitored using solution
1
H NMR spectroscopy. The loading rate of the sulfonyl chloride group
was estimated as 0.50 mmol=g, based on the chlorine elemental analysis.
This reagent was then treated with various a-hydroxyketones in the pres-
ence of triethylamine in dichloromethane to generate the corresponding
PEG-bound a-sulfonyloxy ketones 3, where the polymer species are easily
obtained through precipitation by addition of propan-2-ol to the mix-
tures and simple filtration. The linking reaction to the PEG support
ꢀ
1
was also monitored by the infrared absorption bands at 1371 cm (S-O
ꢀ
1
stretch of-SO C1), which was shifted to 1352 cm (-SO -O-) as well as
2
2
ꢀ1
by the appearance of typical carbonyl absorptions near 1670–1695 cm .
With PEG-bound a-sulfonyloxy ketone 3 in hand, the cyclocondensa-
.
tion reaction of resin 3 with various thioamides, the key for the success of
this protocol, was investigated. To optimize the reaction conditions, sev-
eral solvents such as dichloromethane, acetonitrile, N,N-dimethylforma-
mide, and diethyl ether were used to perform the reaction in our hands.
Scheme 1. Liquid-phase synthesis of thiazoles from PEG-supported sulfonyl
chloride.

3340
X.-L. Liu et al.
After a series of experiments, cyclization of refluxing of acetonitrile in the
[8h]
presence of potassium carbonate, similar to the literature conditions,
was carried out efficiently to furnish the corresponding thiazoles 4 in good
yields, as shown in Table 1. As seen from Table 1, for a-hydroxyketones,
substitution of an electron-withdrawing group or an electron-donating
group on the aromatic ring had no obvious effect on the reaction yields.
However, it is worth noting the yields of thiazoles 4j and 4k (Table 1, entries
13 and 14) were relatively lower under the same reaction conditions, which
might be ascribed to their larger steric restriction of the corresponding
ketones. After finishing the reaction, the recovered PEG-bound sulfonic acid
potassium salt was precipitated with cold diethyl ether and could be
easily converted to PEG-bound sulfonic acid 1 again by treatment with con-
centrated HCl. Therefore, the covered polymeric sulfonic acid 1 can be used
repeatedly for the preparation of the present thiazoles without obvious
decreasing of the yield, as shown in Table 1, entries 1–4.
In conclusion, a mild, efficient, and environmentally benign prepara-
tion of thiazoles from the reaction of a PEG-bound sulfonyl chloride with
a-hydroxyketones, followed by treatment with thioamides in the presence
of potassium carbonate, was successfully carried out. The use of cheap,
recyclable PEG–sulfonyl chloride resin is another advantage of this method.
Table 1. Yields for liquid-phase organic synthesis of thiazoles
1
2
3
a
Entry
R
R
R
Compound
Yield (%)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
C
C H
6
H
5
5
5
5
H
H
H
H
H
H
H
H
H
H
H
H
CH
CH
CH
CH3
3
4a
4a
4a
4a
4b
4c
4d
4e
4f
87
86
b
6
c
C
C
6
H
H
CH
CH
3
3
85
d
85
6
4-MeC H
6
CH3
83
86
80
78
80
81
75
73
65
60
4
4-MeOC
4-ClC
4-NO C H
6
H
4
CH
CH
3
3
6
H
4
CH3
C H
2
6
4
C H
6
5
6
6
6
5
1
1
1
1
1
4-MeOC
4-NO
2-furyl
6
H
4
C
C
H
5
H
5
5
4g
4h
4i
2
C
6
H
4
C H
6
C
4-ClC
6
H
5
3
3
CH
CH
3
4j
4k
6
H
4
3
a
Yields refer to the isolated pure products based on PEG-bound disulfonyl
chloride.
b
With the first regenerated resin.
With the second regenerated resin.
c
d
With the fourth regenerated resin.

Thiazole Synthesis Using Sulfonyl Chloride Resin
EXPERIMENTAL
3341
Melting points were determined on an X melting-point apparatus and are
4
1
uncorrected. H NMR (400 MHz) and C NMR (100MHz) spectra were
13
recorded on a Bruker Avance (400-MHz) spectrometer using CDCl as
3
the solvent and tetramethylsilane (TMS) as an internal standard. Fourier
transform infrared (FT-IR) spectra were taken on a Perkin-Elmer SP One
FT-IR spectrophotometer. PEG-bound sulfonic acid was prepared accord-
[9]
ing to our method. The other reagents were purchased from commercial
sources and were used without further purification. N,N-Dimethylforma-
mide (DMF) was distilled from calcium hydride, and CH Cl was distilled
2
2
from phosphorous pentoxide immediately prior to use.
Procedure for the Preparation of PEG-Bound Sulfonyl Chloride 2
Under a nitrogen atmosphere, DMF (5 mL) was added to PEG 4000 dis-
ulfonic acid 1 (10.0 g, 2.30 mmol) in thionyl chloride (10 mL, 154.3 mmol).
After 16 h with stirring at room temperature, the solvent was removed in
vacuo, and the crude product was dissolved in hot propan-2-ol (100 mL).
ꢁ
The solution was cooled to 0 C, and the precipitate formed was collected
by filtration. The precipitation step was repeated; the combined precipi-
tates were washed with propan-2-ol (10 mL) and Et O (50 mL) and then
2
dried in vacuo to afford PEG-bound sulfonyl chloride 2 as a white solid
1
(
9.50 g, 95%). H NMR (400 MHz, CDCl ) d 3.39–3.89 (m, PEG CH ),
3
2
4
.23 (t, J ¼ 4.6 Hz, 4 H, CH OAr), 7.08 (d, J ¼ 8.9 Hz, 4 H, Ar-H), 7.95
2
(
d, J ¼ 8.9 Hz, 4 H, Ar-H). FT-IR (KBr) t 3032, 2944, 1600, 1545,
ꢀ1
1
371, 1105, 824 cm .
General Procedure for the Preparation of Thiazoles (4a–k)
PEG 4000 disulfonyl chloride 2 (4.35 g, 1.0 mmol) and Et N (2.0 mmol)
3
were added to a solution of a-hydroxy ketone aldehyde (4.0 mmol) in
anhydrous dichloromethane (10.0 mL), and the reaction mixture
was heated at reflux for 24 h under an N atmosphere. The solvent
2
was removed in vacuo, and the crude product was dissolved in hot pro-
pan-2-ol (100 mL). The precipitation step was repeated; the combined
precipitates were washed with propan-2-ol (10 mL) and Et O (50 mL)
2
and then dried in vacuo to afford PEG-bound a-sulfonyloxy ketone 3 as
a white solid in nearly quantitative yield. To a solution of 3 (1.0 mmol)
and thioamide (3.0 mmol) in MeCN (20 mL), K CO (1.24 g, 9 mmol)
2
3
was added, and the reaction mixture was refluxed for 10 h under an N2

3342
X.-L. Liu et al.
atmosphere. The solvent was removed under vacuum, diethyl ether
(200 mL) was added with vigorous stirring, and the mixture was cooled
to 0 C. The resulting precipitate was collected by filtration and washed
ꢁ
with cold diethyl ether (2 ꢂ 20 mL). The filtrate was washed with water
(each of 10 mL) and dried over sodium sulfate. After evaporation of
the solvent, the residue was subjected to column chromatography (silica
gel; hexane–EtOAc, 3:1) to afford pure thiazole 4.
Data
2
-Methyl-4-phenylthiazole (4a)
ꢁ
[11]
ꢁ
1
Mp 64–65 C (lit.
7
1
mp 67 C); H NMR: d ¼ 7.89–7.86 (m, 2 H),
.40–7.33 (m, 3 H), 7.30 (s, 1 H), 2.78 (s, 3 H); IR (KBr): 3130, 2875,
634, 1601, 1510, 1440, 1376, 1080, 922, 745, 695 cm .
ꢀ1
2
-Methyl-4-(4-methylphenyl)thiazole (4b)
ꢁ
[8h]
ꢁ
1
Mp 57–58 C (lit. mp 58–59 C); H NMR: d ¼ 7.77 (d, J ¼ 8.0 Hz, 2 H),
7
.26 (s, 1 H), 7.22 (d, J ¼ 8.0 Hz, 2 H), 2.78 (s, 3 H), 2.38 (s, 3 H); IR
(
KBr): 3133, 2875, 1635, 1600, 1512, 1445, 1378, 1082, 990, 825, 735,
ꢀ1
6
96 cm .
4
-(4-Methoxyphenyl)-2-methylthiazole (4c)
ꢁ
[12]
ꢁ
1
Mp 66–67 C (lit. mp 59–60 C); H NMR: d ¼ 7.80 (d, J ¼ 8.7 Hz, 2 H),
7
.16 (s, 1 H), 6.95 (d, J ¼ 8.7 Hz, 2 H), 3.86 (s, 3 H), 2.78 (s, 3 H); IR
ꢀ
1
(
KBr): 3133, 2872, 1636, 1600, 1510, 1445, 1376, 1078, 842, 768, 692 cm .
4
-(4-Chlorophenyl)-2-methylthiazole (4d)
ꢁ
[11]
ꢁ
1
Mp 110–111 C (lit. mp 110 C); H NMR: d ¼ 7.81 (d, J ¼ 8.8 Hz, 2 H),
7
1
.39 (d,J ¼ 8.8 Hz, 2 H), 7.31 (s, 1 H), 2.77 (s, 3 H); IR (KBr): 3132, 2875,
ꢀ
1
633, 1600, 1511, 1470, 1401, 1172, 1080, 828, 770 cm .
2
-Methyl-4-(4-nitrophenyl)thiazole (4e)
ꢁ
[11]
ꢁ
1
Mp 137–138 C (lit. mp 145 C); H NMR: d ¼ 8.28 (d, J ¼ 8.8 Hz, 2 H),
8
1
.03 (d, J ¼ 8.8 Hz, 2 H), 7.51 (s, 1 H), 2.81 (s, 3 H); IR (KBr): 3133, 2872,
ꢀ
1
636, 1600, 1522, 1500, 1340, 1170, 1090, 841, 765 cm .

Thiazole Synthesis Using Sulfonyl Chloride Resin
3343
2
,4-Diphenylthiazole (4f)
ꢁ
[13]
ꢁ
1
Mp 167–168 C (lit.
H), 7.75–7.73 (m, 2 H), 7.36–7.44 (m, 6 H), 7.28 (s, 1 H); IR (KBr):
mp 168 C); H NMR: d ¼ 8.03 (d, J ¼ 6.8 Hz, 2
ꢀ1
t ¼ 3035, 1640, 1600, 1500, 1455, 1084, 990, 765, 695 cm .
-(4-Methoxyphenyl)-2-phenylthiazole (4g)
4
ꢁ
[14]
ꢁ
1
Mp 123–124 C (lit. mp 124–125 C); H NMR: d ¼ 8.05 (d, J ¼ 8.0 Hz,
2
H), 7.92 (d, J ¼ 8.8 Hz, 2 H), 7.48–7.43 (m, 3 H), 7.35 (s, 1 H), 6.97
(
d, J ¼ 8.8 Hz, 2 H), 3.86 (s, 3 H); IR (KBr): t ¼ 3125, 2875, 1640,
ꢀ1
1
545, 1440, 1375, 1082, 1015, 825, 760 cm .
4
-(4-Nitrophenyl)-2-phenylthiazole (4h)
ꢁ
[8h]
ꢁ
1
Mp 122–123 C (lit. mp 122 C); H NMR: d ¼ 8.30 (d, J ¼ 8.8 Hz, 2 H),
8
3
8
.18 (d, J ¼ 8.8 Hz, 2 H), 8.08–8.04 (m, 2 H), 7.69 (s, 1 H), 7.52–7.46 (m,
H); IR (KBr): t ¼ 3122, 1631, 1599, 1520, 1500, 1342, 1110, 1062, 851,
ꢀ1
42, 744, 690 cm .
4
-(2-Furyl)-2-phenylthiazole (4i)
[
8h]
1
Colorless oil (lit. oil); H NMR: d ¼ 8.02–7.99 (m, 2 H), 7.48–7.45 (m,4
H), 7.42 (s, 1 H), 6.90 (d, J ¼ 3.3 Hz, 1 H), 6.53–6.50 (m, 1 H); IR (film):
ꢀ1
t ¼ 3121, 1621, 1510, 1470, 1088, 991, 881, 732, 683 cm .
2
,4-Dimethyl-4-phenylthiazole (4j)
[
8h]
1
Colorless oil (lit. oil); H NMR: d ¼ 7.61–7.63 (m, 2 H), 7.42–7.31 (m,
3
1
H), 2.67 (s, 3 H), 2.52 (s, 3 H); IR (film): t ¼ 3130, 2870, 1635, 1600,
ꢀ
1
500, 1441, 1386, 1080, 772, 695 cm .
4
-(4-Chlorophenyl)-2,5-dimethylthiazole (4k)
[
8h]
1
Colorless oil (lit.
(
2
oil); H NMR: d ¼ 7.49 (d, J ¼ 8.5 Hz, 2 H), 7.31
d, J ¼ 8.5 Hz, 2 H), 2.57 (s, 3 H), 2.42 (s, 3 H); IR (film): t ¼ 3125,
ꢀ1
869, 1634, 1595, 1500, 1451, 1381, 1089, 996, 761 cm .
ACKNOWLEDGMENT
We gratefully acknowledge financial support from the National Natural
Science Foundation NSF of China (No. 20562005) and NSF of Jiangxi
Province (Nos. 0620021 and 2007GZW0185).

3344
X.-L. Liu et al.
REFERENCES
1
. (a) Dolle, R. E.; Nelson, K. H. Comprehensive survey of combinatorial
library synthesis: 1998. J. Comb. Chem. 1999, 1(4), 235–282; (b) Dolle, R.
E. Comprehensive survey of combinatorial library synthesis: 2000. J. Comb.
Chem. 2001, 3(6), 477–517; (c) Dolle, R. E. Comprehensive survey of combi-
natorial library synthesis: 2002. J. Comb. Chem. 2003, 5(6), 693–753.
. For a review see (a) Gravert, D. J.; Janda, K. D. Organic synthesis on soluble
polymer supports: Liquid-phase methodologies. Chem. Rev. 1997, 97(2),
2
489–510; (b) Wentworth, P.; Janda, K. D. Liquid-phase chemistry: Recent
advances in soluble polymer-supported catalysts, reagents, and synthesis.
Chem. Commun. 1999, 19, 1917–1924; (c) Toy, P. H.; Janda, K. D. Soluble
polymer-supported organic synthesis. Acc. Chem. Res. 2000, 33(8),
5
46–554; (d) Sun, C. M. Soluble polymer-supported synthesis of heterocyclic
libraries. In Combinatorial Chemistry Methods and Protocols; Bellavance L.
Ed.); Humana Press Inc.: NJ, 2002; Chap. 10, pp. 345–371, 546.
(
3
4
. Franz e˙ n, R. G. Recent advances in the preparation of heterocycles on
solid support: A review of the literature. J. Comb. Chem. 2000, 2(3), 195–214.
. Shey, J.; Cun, C. M. Liquid-phase combinatorial reaction monitoring by
1
conventional
725–1729.
H NMR spectroscopy. Tetrahedron Lett. 2002, 43(9),
1
5
. Fink, B. A.; Mortensen, D. S.; Stauffer, S. R.; Aron, Z. D.; Katzenellenbogen,
J. A. Novel structural templates for estrogen-receptor ligands and prospects
for combinatorial synthesis of estrogens. Chem. Biol. 1999, 6(4), 205–219.
. Van Muijlwijk-Koezen, J. E.; Timmerman, H.; Vollinga, R. C.; Von Drabbe
K u¨ nzel, J. F.; De Groote, M.; Visser, S.; Ijzerman, A. P. Thiazole and thia-
diazole analogues as a novel class of adenosine receptor antagonists. J. Med.
Chem. 2001, 44(5), 749–762.
6
7. Metzger, J. V. Comprehensive Heterocyclic Chemistry I; New York: Pergamon
Press, 1984; Vol. 6, p. 328.
8
. (a) Ball, C. P.; Barrett, A. G. M.; Commercon, A.; Comp e` re, D.; Kuhn, C.;
Roberts, R. S.; Smith, M. L.; Venier, O. Chameleon catches in combinatorial
chemistry: Tebbe olefination of polymer-supported esters and the synthesis of
amines, cyclohexanones, enones, methyl ketones, and thiazoles. Chem. Com-
mun. 1998, 18, 2019–2020; (b) Kearney, P. C.; Fernandez, M.; Flygare, J. A.
Solid-phase synthesis of 2-aminothiazoles. J. Org. Chem. 1998, 63(1), 196–
200; (c) Goff, D.; Fernandez, J. The preparation of 2,4-disubstituted thiazoles
on solid support. Tetrahedron Lett. 1999, 40(3), 423–426; (d) Kazzouli, S. E.;
Berteina-Raboin, S.; Mouaddib, A.; Guillaumet, G. Solid support synthesis
of 2,4-disubstituted thiazoles and aminothiazoles. Tetrahedron Lett. 2002,
4
3(17), 3193–3196; (e) Okonya, J. F.; Al-Obeidi, F. Synthesis of 2,5-
dihalothiazole-4-carboxylates. Tetrahedron Lett. 2002, 43(39), 7051–7053;
f) Stieber, F.; Mazitschek, R.; Soric, N.; Giannis, A.; Waldmann, H. Trace-
(
less solid-phase synthesis of 2-aminothiazoles: receptor tyrosine kinase inhi-
bitors with dual selectivity for Tie-2 and VEGFR-2. Angew. Chem. Int. Ed.
2002, 41(24): 4757–4761; (g) Katritzky, A. R.; Cai, X.; Rogovoy, B. V. Solid

Thiazole Synthesis Using Sulfonyl Chloride Resin
3345
phase synthesis and application of trisubstituted thioureas. J. Comb. Chem.
003, 5(4), 392–399; (h) Ueno, M.; Togo, H. Environmentally benign prep-
2
aration of heteroaromatics from ketones or alcohols, with macroporous poly-
styrenesulfonic acid and (diacetoxyiodo)benzene, followed by thioamide,
amidine, and 2-aminopyridine. Synthesis 2004, 16, 2673–2677. (i) Lee, I.
Y.; Lee, J. Y.; Lee, H. J.; Gong, Y.-D. Traceless solid-phase synthesis of
2,4,5-trisubstituted thiazoles. Synlett 2005, 16, 2483–2485.
9
. Wang, Q.-Y.; Sheng, S.-R.; Wei, M.-H.; Xie, Z.-L.; Liu, X.-L. PEG-
supported sulfonic acid as an efficient and recyclable catalyst for the synthesis
of 1,1-diacetates under solvent-free conditions. Synth. Commun. 2007, 37(6),
1019–1026.
1
0. (a) Sieber, F.; Wentworth, P.; Toker, J. D.; Wentworth, A. D.; Metz, W. A.;
Reed, N. N.; Janda, K. D. Development and application of a poly(ethylene
glycol)–supported triarylphosphine reagent: Expanding the sphere of liquid-
phase organic synthesis. J. Org. Chem. 1999, 64(14), 5188–5192; (b) Behrendt,
J. M.; Bala, K.; Golding, P.; Hailes, H. C. Oxetane synthesis via cyclisation
of aryl sulfonate esters on polystyrene and PEG polymeric supports.
Tetrahedron Lett. 2005, 46(4), 643–645.
1
1. Kar, J. N.; Acharya, R. C.; Rout, M. K.Quaternization of thiazoles. J. Org.
Chem. 1973, 38(12), 2164–2166.
1
2. Grabmann, S.; Sadek, B.; Ligneau, X.; Elz, S.; Ganellin, C. R.; Arrang, J. M.;
Schwartz, J. C.; Stark, H.; Schunack, W. Progress in the proxifan class:
Heterocyclic congeners as novel potent and selective histamine H -receptor
3
antagonists. Eur. J. Pharm. Sci. 2002, 15(4), 367–378.
1
3. Ishida, M.; Nakanashi, H.; Kato, S. Novel cyclization of 2-(hydroxymino)-2-
phenylethyl dithiocarboxylates. Chem. Lett. 1984, 13(10), 1691–1692.
4. Maeda, M.; Kojima, M.Mechanism of the photorearrangements of
phenylthiazoles. J. Chem. Soc., Perkin Trans. 1 1978, 7, 685–692.
1