Facile one-pot synthesis of three different substituted thiazoles from propargylic alcohols

Article abstract of DOI:10.1039/c002093a

Three different substituted thiazoles have been successfully synthesized from readily available propargylic alcohols. Various secondary propargylic alcohols or tertiary propargylic alcohols participated well in the reaction, providing the desired products in good yields. This method provides a flexible and rapid route to substituted thiazoles. The Royal Society of Chemistry 2010.

Full text of DOI:10.1039/c002093a

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Facile one-pot synthesis of three different substituted thiazoles from
propargylic alcohols†
Xun Gao, Ying-ming Pan, Min Lin, Li Chen and Zhuang-ping Zhan*
Received 25th February 2010, Accepted 26th April 2010
First published as an Advance Article on the web 25th May 2010
DOI: 10.1039/c002093a
Three different substituted thiazoles have been successfully synthesized from readily available
propargylic alcohols. Various secondary propargylic alcohols or tertiary propargylic alcohols
participated well in the reaction, providing the desired products in good yields. This method provides a
flexible and rapid route to substituted thiazoles.
Introduction
Thiazole natural products, such as the mycothiazole,1 cystothia-
zole A2 and WS75624 B,3 are a diverse and biologically significant
class of compounds in which there has been considerable interest.
Because these and other natural products and pharmaceuticals
containing thiazole ring, there has been intense development of
methodology to construct such moieties.4,5 Approaches toward
functionalized thiazoles can be divided into two groups: function-
alization of a preexisting heterocyclic core, and assembly of the
ring from acyclic precursors. Among the two, the latter route has
greater potential for rapidly obtaining diversity in functionalized
heterocycles. Within this group, Hantzsch thiazole synthesis has
proven to be a powerful method for the synthesis of thiazoles.6
Scheme 1 Synthesis of three different substituted thiazoles.
Despite the advances realized, more flexible and general routes
to a variety of functionalized thiazoles are needed.7 In particular,
techniques that can readily give access to thiazoles with a diverse
and easily manipulated set of substituents are still of critical
importance.
Results and discussion
Initially, propargylic alcohol 1a and thiobenzamide 2a were treated
with 1 equiv. of PTSA in chlorobenzene at reflux. Surprisingly,
this reaction didn’t produce the desired product 6aa, but 4-benzyl-
2,5-diphenylthiazole 3aa, which was obtained through an allenyl
cation, and not a propargylic cation intermediate, albeit in only
12% yield (Table 1, entry 1). To further optimize the reaction
shown in Table 1, we first investigated a variety of catalysts for
their effectiveness at catalyzing this reaction. With other Brønsted
acids, such as oxalic acid, no reaction was observed (Table 1,
entry 2). We reasoned that the poor catalyst activity of Brønsted
acids might be ascribed to their strong acidity. Accordingly, we
began searching for appropriate Lewis acids, which would readily
catalyze the cycloaddition reaction. Gratifyingly, switching the
catalyst to 10 mol% AgOTf furnished the substituted thiazole 3aa
in 92% yield after 0.2 h at reflux (Table 1, entry 3). Notably, a longer
reaction time is required when the catalytic amount of AgOTf
decreased from 10 to 5 mol% (Table 1, entry 13 vs. entry 3). With
AgBF4 and AgSbF6, the cycloaddition also proceeded smoothly
to afford the thiazole 3aa in good yields (Table 1, entries 11 and
12). Cu(OTf)2 effectively promoted the cycloaddition reaction,
although a somewhat long reaction time was needed (Table 1, entry
7). However, with Sc(OTf)3, the cycloaddition reaction afforded
the substituted thiazole in undesired yields (Table 1, entries 9 and
10).10 In addition, it was found that the solvent played a crucial
role in this cycloaddition reaction (Table 1, entries 3, 14–20).
Toluene, 1,2-dichloroethane and nitromethane as solvents were
We have recently reported an efficient one-pot propargy-
lation/cycloisomerization tandem process for the synthesis of
substituted oxazole derivatives from propargylic alcohols and
amides employing p-toluenesulfonic acid monohydrate (PTSA)
as a bifunctional catalyst.8 We envisioned that replacement of
the amides with thioamides would allow for the cycloaddition
reaction of propargyl alcohols with thioamides to afford sub-
stituted thiazoles.9 Herein, we describe novel methods for the
synthesis of three different substituted thiazoles from propargylic
alcohols (Scheme 1). A wide range of secondary propargylic
alcohols or tertiary propargylic alcohols bearing not only terminal
alkyne groups but also internal alkyne groups can effectively be
employed, and a number of functional groups, such as cyclopropyl,
cyclohexenyl, bromo, chloro, ester and methoxy, are tolerated
under the reaction conditions.
Department of Chemistry, College of Chemistry and Chemical Engineering,
and State Key Laboratory for Physical Chemistry of Solid Surfaces,
Xiamen University, Xiamen 361005, Fujian, P. R. China. E-mail: zpzhan@
xmu.edu.cn
† Electronic supplementary information (ESI) available: Experimental
procedures, spectral data for all compounds together with copies of 1H and
13C NMR spectra of all new compounds, and X-ray data for compound
3fa. CCDC reference number 751760. For ESI and crystallographic data
in CIF or other electronic format see DOI: 10.1039/c002093a
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Table 1 Optimization of substituted thiazole formationa
Entry
Catalyst
Solvent
Time/h
Yield [%]b
1c
2c
3
4
5
6
7
8
9
10
11
12
13d
14
15
16
17
18
19
20
PTSA
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
1
12
0
92
23
51
0
86
28
53
38
85
81
84
78
68
81
76
0
Oxalic acid
AgOTf
BiCl3
InCl3
FeCl3
24
0.2
1
1
12
1
1
1
1
0.5
1
Cu(OTf)2
Zn(OTf)2
Sc(OTf)3
Sc(OTf)3
AgSbF6
AgBF4
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
PhCl
CH3NO2–H2O (10 : 1)
PhCl
PhCl
PhCl
3
4
4
4
Toluene
CH3CN
DCE
CH3NO2
DCM
THF
Acetone
1
24
24
24
33
29
a Reaction conditions: 10 mol% of catalyst, 1.0 equiv. of 1a (0.5 mmol), and 1.2 equiv. of 2a (0.6 mmol) in solvent (2 mL) at reflux. b Isolated yield of pure
product based on propargylic alcohol 1a. c 1.0 equiv. d 5 mol% AgOTf.
also able to facilitate the cycloaddition reaction. However, the
use of chlorobenzene instead of toluene, 1,2-dichloroethane and
nitromethane obviously reduced the reaction time (Table 1, entry 3
vs. entries 14, 16 and 17). The results of solvents screened showed
that the reaction rates were influenced by various factors, such
as boiling point, polarity, etc. Because the cycloaddition reaction
proceeded under reflux, the boiling point of solvents might be a
main factor. However, the detailed mechanism is still not clear.
With these optimal reaction conditions in hand, we examined
the scope of this cycloaddition reaction. Typical results are shown
in Table 2. To our delight, all the secondary propargylic alcohols
and tertiary propargylic alcohols 1 bearing not only terminal
alkyne groups but also internal alkyne groups participated well in
the cycloaddition reaction, producing the cycloaddition products
in good yields. The reaction is completed rapidly under mild
conditions and is tolerant to air, giving water as the only
byproduct. It should also be noted that groups such as cyclopropyl,
cyclohexenyl, bromo, ester, and methoxy in the propargylic
alcohols were readily carried through the cycloaddition reaction,
allowing for the subsequent elaboration of the products.
Secondary propargylic alcohol 1h possessing an electron-
donating group at the aryl ring reacted smoothly with thioamide
2a affording the thiazole 3ha in 94% yield (Table 2, entry 8).
Moreover, substrates 1i and 1j possessing electron-withdrawing
groups (bromo and ester functionalities) at the aryl ring were
also successfully employed in the cycloaddition reaction to give
the thiazoles 3ia and 3ja in 85 and 74% yields with complete
regioselectivity, respectively (Table 2, entries 9 and 10). Obviously,
electron-rich propargylic alcohols provided the desired products in
higher yields than electron-poor propargylic alcohols. Secondary
propargylic alcohols possessing a straight chain saturated alkyl
on the alkyne part (R3 = n-Bu) reacted rapidly with a series of
thioamides, providing the corresponding cycloaddition products
in high yields with complete regioselectivity (Table 2, entries 2,
5, 7–9, 16 and 18–21). Remarkably, the expected cyclopropyl
thiazoles (R3 = cyclopropyl) were obtained readily, and no ring-
opening of the cyclopropyl groups was observed (Table 2, entries 3
and 24). When R3 is an olefin, the cycloaddition also led to the for-
mation of the thiazoles (R3 = cyclohexenyl) in good yields (Table 2,
entries 4 and 25). Additionally, heteroaromatic propargylic alcohol
1e and fused aromatic propargylic alcohol 1g readily underwent
cycloaddition reaction to afford the substituted thiazoles 3ea and
3ga in desired yields with complete regioselectivity, respectively
(Table 2, entries 5 and 7). Most notably, secondary propargylic
alcohol 1f containing a substituted olefin that is susceptible to
protonation also reacted smoothly with thioamide to give 3fa
in 71% yield with complete regioselectivity (Table 2, entry 6).
The crystallization of compound 3fa from ethanol gave single
crystals suitable for X-ray analysis. Fig. 1 illustrates the molecular
structure of the substituted thiazole 3fa.11 The X-ray structure
of 3fa shows the expected five-membered (C11–S1–C12–N1–C10)
aromatic ring skeleton. Thiazole 3fa adopts a trans-configuration,
in which the two hydrogen atoms are on opposite side of the double
=
bond (C7 C8). The X-ray crystal structure also reveals that the
dihedral angle between plane 1 (defined by atoms C13–C18) and
plane 2 (S1, N1 and C10–C12) is 18.66 (0.28)◦, and the dihedral
angle between plane 2 (S1, N1 and C10–C12) and plane 3 (C19–
C24) is 47.04 (0.2)◦.
Tertiary propargylic alcohols could also participate in the
cycloaddition with thioamide using silver triflate as a catalyst
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Table 2 Synthesis of substituted thiazoles 3aa–3dh from propargylic alcohols 1a–1o and thioamides 2a–2ha
Entry
1
R1; R2; R3
R4
Product
Time/h
0.2
Yield [%]b
92
1a: Ph; H; Ph
2a: Ph
3aa
2
1b: Ph; H; n-Bu
2a: Ph
3ba
0.5
87
3
4
1c: Ph; H; cyclopropyl
2a: Ph
2a: Ph
3ca
3da
0.3
0.3
89
90
1d: Ph; H; 1-cyclohexenyl
5
1e: 2-Thienyl; H; n-Bu
2a: Ph
3ea
0.5
88
=
6
7
1f: (trans)PhCH CH; H; Ph
2a: Ph
2a: Ph
3fa
0.4
0.4
71
88
1g: 1-Naphthyl; H; n-Bu
1h: 2-MeOPh; H; n-Bu
3ga
8
9
2a: Ph
2a: Ph
3ha
3ia
0.2
0.5
94
85
1i: 4-BrPh; H; n-Bu
10
11
1j: 4-MeOOCPh; H; Ph
1k: Ph; Ph; Ph
2a: Ph
2a: Ph
3ja
1
74
95
3ka
0.2
12
13
1l: Ph; Me; TMS
1m: Ph; Me; H
2a: Ph
2a: Ph
3la
3la
0.2
0.3
89
83
14c
15c
1n: Me; Me; Ph
1o: -(CH2)5-; Ph
2a: Ph
2a: Ph
3na
3oa
24
24
58
42
16
17
1b: Ph; H; n-Bu
1a: Ph; H; Ph
2b: 4-MeOPh
2c: 4-CH3Ph
3bb
3ac
0.5
0.2
89
91
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Table 2 (Contd.)
Entry
18
R1; R2; R3
R4
Product
Time/h
0.8
Yield [%]b
84
1b: Ph; H; n-Bu
2d: 4-ClPh
3bd
19
20
21
1b: Ph; H; n-Bu
2e: 4-NO2Ph
2f: Me
3be
3bf
3bg
1
1
1
68
77
82
1b: Ph; H; n-Bu
1b: Ph; H; n-Bu
2g: i-Pr
22
23
1a: Ph; H; Ph
1m: Ph; Me; H
2f: Me
3af
1
1
80
79
2h: n-Pr
3mh
24
25
1c: Ph; H; cyclopropyl
2h: n-Pr
2h: n-Pr
3ch
3dh
1
1
83
86
1d: Ph; H; 1-cyclohexenyl
a Reaction conditions: 1 (0.5 mmol), 2 (0.6 mmol), and AgOTf (0.05 mmol) in chlorobenzene (2 mL) at reflux. See the ESI for details.† b Isolated yield of
pure product based on propargylic alcohols 1. c The solvent is nitromethane.
tertiary aliphatic propargylic alcohols 1n and 1o also reacted with
thioamide affording thiazoles 3na and 3oa in moderate yields with
complete regioselectivity (Table 2, entries 14 and 15). This is in
sharp contrast to the Sc-catalyzed reaction7 where the substrates
are limited to the secondary aromatic propargylic alcohols (R1 =
aryl, R2 = H, R3 = SPh or SePh). The results suggested that
the cycloaddition proceeded through a cationic intermediate and
the yield of the cycloaddition reaction was dependent on the
stability of the cationic intermediate. Instability of the cationic
intermediate of the tertiary aliphatic propargylic alcohols made
the cycloaddition reaction less favorable.
A variety of thioamides 2 were also employed to examine the
generality of the method. Both aromatic thioamides and aliphatic
thioamides could be efficiently incorporated into the thiazole
framework. The cycloaddition reaction proceeded smoothly when
the aryl groups of the aromatic thioamides were substituted with
electron-donating (Table 2, entry 16) and electron-withdrawing
groups (Table 2, entry 19). Electron-rich groups are beneficial to
the cycloaddition reaction. Aliphatic thioamides required slightly
longer reaction times, but maintained high yields (Table 2, entries
20–25).
Interestingly, Table 3 shows that the attempted cycloaddition
of secondary propargylic alcohols 1p–1t (R3 = TMS or H)
Fig. 1 X-ray crystal structure of thiazole 3fa. The thermal ellipsoids are
at the 50% probability level.
(Table 2, entries 11–15). 10 mol% AgOTf catalyzed the selective
cycloaddition of tertiary aromatic propargylic alcohols 1k–1m and
thioamide, affording 3 in high yields (Table 2, entries 11–13). The
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Table 3 Synthesis of substituted thiazoles 3pa–3ta and 4pa–4ta from propargylic alcohols 1p–1t and thioamides 2a
Product
Entry
1
Propargylic alcohol
Thioamide
3
4
Time/h
1
Yield [%]b (ratio 3 : 4)c
1p: R1 = Ph; R3 = TMS
2a: R4 = Ph
3pa
4pa
87 (29 : 71)
2
3
1p: R1 = Ph; R3 = TMS
1q: R1 = Ph; R3= H
2f: R4 = Me
2a: R4 = Ph
3pf
4pf
2
83 (24 : 76)
76 (8 : 92)
3pa
4qa
1.5
4
5
6
1r: R1 = 4-ClPh; R3 = TMS
1s: R1 = 4-ClPh; R3 = H
2h: R4 = n-Pr
2a: R4 = Ph
3rh
3sa
3ta
4rh
4sa
4ta
2
2
1
79 (21 : 79)
72 (7 : 93)
89 (75 : 25)
1t: R1 = 1-Naphthyl; R3 = TMS 2a: R4 = Ph
a Reaction conditions: 1 (0.5 mmol), 2 (0.6 mmol), and AgOTf (0.05 mmol) in chlorobenzene (2 mL) at reflux. See the ESI for details.† b Isolated yield of
pure product based on propargylic alcohols 1. c Determined by 1H NMR.
with thioamides led to the formation of the substituted thi-
azoles 4 as the major products, and the substituted thiazoles
3 were observed as only the minor products. Remarkably, the
structure of the substituted thiazoles 4 differed from that of the
substituted thiazoles 3. Typical results are depicted in Table 3.
Secondary propargylic alcohols (R3 = TMS) reacted smoothly
with thioamides 2 affording the substituted thiazoles 3 and 4
in high yields with moderate selectivity (3 : 4 = 21 : 79–75 : 25)
(Table 3, entries 1, 2, 4 and 6). The trimethylsilyl group attached
to the thiazole ring could not be tolerated under the acidic
conditions and had fallen off during work-up. Notably, with
the use of secondary terminal propargylic alcohols (R3 = H) as
substrates, the regioselectivity of the cycloaddition reaction was
greatly improved. For example, secondary terminal propargylic
alcohol 1q (R3 = H) readily underwent cycloaddition to give the
substituted thiazoles 3pa and 4qa in total yield of 76% with high
selectivity (3pa : 4qa = 8 : 92) (Table 3, entry 3). The cycloaddition
reaction of propargylic alcohols bearing terminal alkyne (R3 =
H) with thioamides showed high regioselectivity toward the sub-
stituted thiazoles 4, and provided a rapid route to the substituted
thiazoles 4.
propargylic alcohol 1a (0.5 mmol) was treated with amide 5a
(0.55 mmol) in the presence of 10 mol% FeCl3 in acetonitrile.
Upon reaction completion, acetonitrile was removed in vacuo,
followed by the addition of toluene (2 mL) and Lawesson’s reagent
(0.55 mmol). The reaction was heated to reflux for 10 h. The
desired product 6aa was obtained in 50% yield. Typical results
are depicted in Table 4. Various secondary aromatic propar-
gylic alcohols participated well in the reaction, providing the
propargylation/sulfuration/cyclization products with complete
regioselectivity. Both aromatic amides (Table 4, entries 1–3 and
5–8) and aliphatic amides (Table 4, entry 4) could be efficiently
incorporated into the thiazole framework. It should be noted that
the structure of the substituted thiazoles 6 differed completely
from that of the substituted thiazoles 3 and 4. Formation of
product 6pe was also observed by treating compound 14a with
Lawesson’s reagent in the absence of 10 mol% FeCl3 (Scheme 2).
This result clearly showed that FeCl3 was not essential in the
cyclization step of the sequential reactions.
As results of the development on the transition metal-
catalyzed nucleophilic substitution of propargylic alcohols in
our group,12 we wish to report a highly efficient propar-
gylation/sulfuration/cyclization reaction for the synthesis of
substituted thiazoles directly from propargylic alcohols, amide
and Lawesson’s Reagent (2,4-bis-(4-methoxyphenyl)-1,3-dithia-
2,4-diphosphetane-2,4-disulfide), as shown in Table 4. Initially,
Scheme 2 Reactions of alkynyl-amide 14a with Lawesson’s reagent.
On the basis of these data, we propose the process detailed in
Scheme 3 as the most likely mechanism for this transformation.
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Table 4 Synthesis of substituted thiazoles 6 from propargylic alcohols 1 and amides 5a
Entry
1
R1; R3
R4
Product
Time/hb
17
Yield [%]c
50
1a: Ph; Ph
5a: Ph
6aa
2
3
4
5
1a: Ph; Ph
1a: Ph; Ph
1a: Ph; Ph
1b: Ph; n-Bu
5b: 4-MeOPh
5c: 4-ClPh
5d: n-Pr
6ab
6ac
6ad
6ba
17
17
17
17
53
47
41
46
5a: Ph
6
7
8
1p: Ph; TMS
1p: Ph; TMS
1p: Ph; TMS
5b: 4-MeOPh
5e: 4-CH3Ph
5f: 4-BrPh
6pb
6pe
6pf
20
20
20
51
50
47
a Reaction conditions: 1 (0.5 mmol), 5 (0.55 mmol), and FeCl3 (0.05 mmol) in CH3CN (2 mL) at 70 ◦C for 7 h, or at 80 ◦C for 10 h (for substrate
1p). Upon reaction completion, acetonitrile was removed in vacuo, followed by the addition of toluene (2 mL) and Lawesson’s reagent (0.6 mmol).
Cycloisomerization proceeded at reflux for 10 h. b Overall teaction time for three steps. c Isolated yield of pure product based on propargylic alcohols 1.
For the silver-catalyzed cycloaddition reaction of propargylic
alcohols with thioamides, the propargylic cation 7 or the allenyl
cation 8 is attacked firstly by the sulfur atom of the thioamides.
The secondary propargylic alcohols (R3 = alkyl or aryl) or tertiary
propargylic alcohols follow path A. In path A, the ionization
of propargylic alcohol 1 would firstly lead to propargylic cation
7. The propargyl cation would isomerize to the allenyl cation 8
and the subsequent nucleophilic attack of the thioamide 2 gives
intermediate 9, which easily cyclizes in the 5-exo-dig mode, leading
to the thiazole 3. At the same time, the secondary propargylic
alcohols (R3 = TMS or H) follow both path A and path B, but
cycloaddition proceeds mainly via path B. When the secondary
propargylic alcohols (R3 = TMS or H) are used, instability of
the allenyl cation intermediate 8 (R3 = H) and the steric effect
of trimethylsilane group at g-position of the intermediate 8 (R3 =
TMS) makes path A less favorable. Accordingly, the cycloaddition
would also proceed through path B, which is more favorable. In
path B, the reaction of the propargylic cation 7 and the thioamide
2 gives intermediate 10. Coordination of cationic silver(I) to the
alkyne forms the p-alkyne silver complex 11 and enhances the
electrophilicity of the alkyne. Subsequent 5-exo-dig nucleophilic
attack of the amido group would generate the alkenyl-silver
derivative 12. Protonolysis of 12 affords dihydrothiazole 13, which
then undergoes isomerization to the thiazole 4.
Nevertheless, secondary propargylic alcohol 1t (R1 = naphthyl,
R3 = TMS) reacted rapidly with thiobenzamide to produce the
thiazole 3ta as a major product (Table 2, entry 6), possibly
due to the steric bulkiness of the naphthyl group at the a-
position of the intermediate 7. On the other hand, for the
propargylation/sulfuration/cyclization reaction of propargylic
alcohols, amide and Lawesson’s Reagent, the propargylic cation 7
is attacked firstly by the nitrogen atom of the amides. In path
C, propargylic cation 7 underwent nucleophilic attack of the
amide 5, giving alkynyl-amide 14, which was easily converted to
alkynyl-thioamide 15 in the present of Lawesson’s Reagent. The
subsequent cycloisomerization of 15 gives the final product 6.
In addition, the silver-catalyzed cycloaddition reaction also
proceeded well with symmetrical propargylic alcohols, allowing
for the synthesis of oligomers containing two thiazole moieties. For
example, symmetrical propargylic alcohol 1u underwent silver-
catalyzed cycloaddition reaction to afford the oligomer 3ua in
71% isolated yield with complete regioselectivity (Scheme 4). This
process has the potential to access oligoaryls that show promise
as new optoelectronic materials.13
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Scheme 3 Proposed mechanism for the synthesis of three different substituted thiazoles.
a Perkin–Elmer 2400 microanalyser. Flash chromatography was
performed with QingDao silica gel (300–400 mesh).
General procedure for the synthesis of substituted thiazoles 3
and 4. To a 5 mL flask, propargylic alcohols14 1 (0.5 mmol),
thioamides15 2 (0.6 mmol), chlorobenzene (2.0 mL) and AgOTf
(0.05 mmol) were successively added. The reaction mixture was
stirred at reflux, and monitored periodically by TLC. Upon
completion, the chlorobenzene was removed under reduced pres-
sure, and then the residue was purified by silica gel column
chromatography (EtOAc–hexane) to afford the corresponding
substituted thiazoles 3 (or two regioisomers 3 and 4).
Scheme 4 Synthesis of the oligomer 3ua.
Conclusions
In summary, three different substituted thiazoles have been suc-
cessfully synthesized from readily available propargylic alcohols.
The reaction is proposed to proceed through an allenyl isomer or
propargylic cation intermediate. The readily available substrates,
broad scope and operational simplicity of this process should be
beneficial for its large-scale application. Study on the development
of the cycloaddition reaction is ongoing in our laboratory.
General procedure for the synthesis of substituted thiazoles 6.
To a 5 mL flask, propargylic alcohols 1 (0.5 mmol), amides 5
(0.55 mmol), acetonitrile (2.0 mL) and FeCl3 (0.05 mmol) were
successively added. The reaction was allowed to stir at 70–80 ◦C,
and monitored periodically by TLC. Upon reaction completion,
acetonitrile was removed in vacuo, followed by the addition of
toluene (2 mL) and Lawesson’s reagent (0.55 mmol). The reaction
mixture was heated to reflux temperature for an additional 10 h
until completion. Upon completion, the toluene was removed
under reduced pressure, and then the residue was purified by
silica gel column chromatography (EtOAc–hexane) to afford the
corresponding substituted thiazoles 6.
Experimental
General experimental
Propargylic alcohols 1 and thiobenzamides 2 were prepared
according to published procedures. All other compounds are
commercially available and were used without further purification.
Infrared spectra were recorded on a Nicolet AVATER FTIR360
spectrometer. NMR spectra were recorded on a Bruker AVANCE
DPX-400 instrument at 400 MHz (1H) or 100 MHz (13C). The
chemical shift values (d) are given in parts per million (ppm)
and are referred to the residual peak of the deuterated solvent
(CDCl3). MS measurements were performed on Bruker Reflex
III mass spectrometer. Elemental analyses were performed with
Acknowledgements
The research was financially supported by the National Natural
Science Foundation of China (No. 20772098) and the Program for
New Century Excellent Talents in Fujian Province University.
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9 Recently, the Nishibayashi team has tried to obtain the thiazoles by the
reaction of propargylic alcohols with thiobenzamide in the presence
of ruthenium and gold catalysts, but it was unsuccessful. See: M. D.
Milton, Y. Inada, Y. Nishibayashi and S. Uemura, Chem. Commun.,
2004, 2712.
10 In the Sc(OTf)3-catalyzed propargylations and cycloaddition of 3-
sulfanylpropargyl alcohols or 3-selanylpropargyl alcohols, g -sulfanyl
or g -selanyl functional groups play an important role. Either the sulfur
or the selenium atom stabilizes the propargyl cation and the allenyl
cation, and promotes the propargylations and cycloaddition, e.g. See:
Notes and References
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(a) M. Yoshimatsu, T. Otani, S. Matsuda, T. Yamamoto and A. Sawa,
Org. Lett., 2008, 10, 4251; (b) ref. 7.
11 Crystal data for 3fa: C24H19NS, M = 353.46, orthorhombic, space
˚
˚
˚
group Fdd2, a = 17.699(4) A, b = 74.502(18) A, c = 5.7208(14) A, a =
◦
◦
◦
3
-3
˚
90 , b = 90 , g = 90 , V = 7544(3) A , Z = 16, Dc = 1.245 Mg m ,
m = 0.178 mm-1, 14565 reflections, 3678 unique (Rint = 0.1042), R[F2 >
2s(F2)] = 0.0722, wR(F2) = 0.2081, Flack value = 0.02(18). CCDC
751760.
12 We have reported that the FeCl3-catalyzed nucleophilic substitution of
propargylic alcohols with amides in acetonitrile affords the alkynyl-
amides in good yields. See: Z.-P. Zhan, J.-L. Yu, H.-J. Liu, Y.-Y.
Cui, R.-F. Yang, W.-Z. Yang and J.-P. Li, J. Org. Chem., 2006, 71,
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6 T. Eicher and S. Hauptmann, The Chemistry of Heterocycles: Struc-
tures, Reactions, Synthesis, and Applications, Wiley-VCH, Weinheim,
2nd edn, 2003.
7 During the preparation ofthis manuscript,
a Sc(OTf)3-catalyzed
13 (a) C.-F. Lee, L.-M. Yang, T.-Y. Hwu, A.-S. Feng, J.-C. Tseng and T.-Y.
Luh, J. Am. Chem. Soc., 2000, 122, 4992; (b) J. F. Hulvat, M. Sofos,
K. Tajima and S. I. Stupp, J. Am. Chem. Soc., 2005, 127, 366; (c)
M. Sato and A. Yoshizawa, Adv. Mater., 2007, 19, 4145.
14 The propargyl alcohols were prepared from aldehyde or ketone and
alkyne. See: M. Egi, Y. Yamaguchi, N. Fujiwara and S. Akai, Org.
Lett., 2008, 10, 1867.
cycloaddition reaction of 3-sulfanylpropargyl alcohols or 3-
selanylpropargyl alcohols with thioamides was reported. However, the
substrates of this method are limited to the secondary aromatic 3-
sulfanylpropargyl alcohols or secondary aromatic 3-selanylpropargyl
alcohols. See: M. Yoshimatsu, T. Yamamoto, A. Sawa, T. Kato, G.
Tanabe and O. Muraoka, Org. Lett., 2009, 11, 2952.
8 Y.-M. Pan, F.-J. Zheng, H.-X. Lin and Z.-P. Zhan, J. Org. Chem., 2009,
74, 3148.
15 The thioamides were prepared from amides and Lawesson’s reagent.
See: S. J. Coats, J. S. Link and D. J. Hlasta, Org. Lett., 2003, 5, 721.
3266 | Org. Biomol. Chem., 2010, 8, 3259–3266
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