Tert -Butoxide-Assisted Structural Transformation of 2-Aza-1,3,5-trienes: Fast Track to 5-Ethynyl-2-vinyl- and 2,5-Divinyl-1,3-thiazoles

Article abstract of DOI:10.1055/s-0037-1609561

Treatment of 2-aza-1,3,5-trienes, methyl N -[2-alkoxy-1-(prop-2-ynylsulfanyl)buta-1,3-dienyl]- and methyl N -[1-(allylsulfanyl)-2-alkoxybuta-1,3-dienyl]iminoformates, which are easily obtained from lithiated alkoxyallenes, methoxymethyl isothiocyanate, and propargyl or allyl bromide, with t -BuOK or t -BuONa in DMSO-THF results in the formation of 5-ethynyl-2-vinyl- and 2,5-divinyl-1,3-thiazoles. The reactions are realized under mild conditions at ca. -30 °C for 30 minutes. An unprecedented structural transformation of the (prop-2-ynylsulfanyl)- and (allylsulfanyl)-substituted 2-aza-1,3,5-trienes into 1,3-thiazoles presumably occurs via α-deprotonation of the substituent at the sulfur atom (on the SCH ₂ group) followed by intramolecular [1,5]-cyclization at the imine group and aromatization (with elimination of MeOH).

Full text of DOI:10.1055/s-0037-1609561

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–L
paper
A
en
N. A. Nedolya et al.
Paper
Synthesis
tert-Butoxide-Assisted Structural Transformation of 2-Aza-1,3,5-
trienes: Fast Track to 5-Ethynyl-2-vinyl- and 2,5-Divinyl-1,3-thi-
azoles
N
Nina A. Nedolya*
Ol’ga A. Tarasova
Alexander I. Albanov
Boris A. Trofimov*
OR1
Me
R2 = C CH
S
1. n-BuLi
THF–hexane
t-BuOK
DMSO–THF
ca. –30 °C
30 min
OMe
N
2. MeOCH2N=C=S
3. R2CH2Br
5 examples
22–46% yield
Z/E = ca. 100:0–89:11
OR1
•
R2
H2O
S
One-Pot
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian
Branch, Russian Academy of Sciences, Favorsky Street 1,
664033 Irkutsk, Russian Federation
nina@irioch.irk.ru
OR1
R2 = CH=CH2
N
OR1
boris_trofimov@irioch.irk.ru
S
Me
5 examples
16–44% yield
Z/E = ca. 100:0–83:17
R1 = Me, Et, n-Bu, EtOCH(Me), FeCH2
Received: 21.05.2018
Accepted after revision: 18.06.2018
Published online: 22.08.2018
2,3-dienimidothioates 1 (1-aza-1,3,4-trienes) in good to ex-
cellent yields (Scheme 1).5,6 Under mild heating (or even
upon storage), 1-aza-1,3,4-trienes easily isomerize into
conjugated 2-aza-1,3,5-trienes 2 (via a [1,5]-H shift). Con-
current formation of 3-alkoxy-1-alkyl-2-(alkylsulfanyl)pyr-
roles 3 (via intramolecular [1,5]-heterocyclization of 1-aza-
1,3,4-trienes 1) is also observed. Heating 2-aza-1,3,5-
trienes 2 at higher temperatures leads to 5-alkoxy-6-(alkyl-
sulfanyl)-2,3-dihydropyridines 4 (via 6-azaelectrocycliza-
tion), while their treatment with potassium tert-butoxide
[1.2–1.5 equiv, DMSO–THF (ca. 1:5), ca. –30 °C, 30 min] un-
expectedly furnishes 3-alkoxy-2-(alkylsulfanyl)-4,5-dihy-
dro-3H-azepines 5 and 6-alkoxy-3H-azepines 6 (via depro-
tonation on the ketimine fragment, accompanied by [1,7]-
electrocyclization) (Scheme 1).7
DOI: 10.1055/s-0037-1609561; Art ID: ss-2018-z0354-op
Abstract Treatment of 2-aza-1,3,5-trienes, methyl N-[2-alkoxy-1-
(prop-2-ynylsulfanyl)buta-1,3-dienyl]- and methyl N-[1-(allylsulfanyl)-2-
alkoxybuta-1,3-dienyl]iminoformates, which are easily obtained from
lithiated alkoxyallenes, methoxymethyl isothiocyanate, and propargyl
or allyl bromide, with t-BuOK or t-BuONa in DMSO–THF results in the
formation of 5-ethynyl-2-vinyl- and 2,5-divinyl-1,3-thiazoles. The reac-
tions are realized under mild conditions at ca. –30 °C for 30 minutes. An
unprecedented structural transformation of the (prop-2-ynylsulfanyl)-
and (allylsulfanyl)-substituted 2-aza-1,3,5-trienes into 1,3-thiazoles pre-
sumably occurs via -deprotonation of the substituent at the sulfur
atom (on the SCH2 group) followed by intramolecular [1,5]-cyclization
at the imine group and aromatization (with elimination of MeOH).
Key words alkoxyallenes, methoxymethyl isothiocyanate, 2-aza-
1,3,5-trienes, deprotonation, intramolecular cyclization, aromatization,
5-ethynyl-2-vinyl-1,3-thiazoles, 2,5-divinyl-1,3-thiazoles
One-Pot:
OR1
R1O
1. n-BuLi
THF–hexane
OR1
SR4
R3
Δ
•
•
SR4
2. R2R3CHN=C=S
3. R4X
N
N
Azatrienic systems are useful intermediates in the syn-
thesis of both heterocyclic and open-chain polyfunctional-
ized compounds.1 But there are only a few approaches
described in the literature for the synthesis of stable and
isolable 2-aza-1,3,5-trienes,2 which can serve as useful pre-
cursors of important azaheterocycles including pyrroles,
pyridines, dihydropyridines, azepines, cyclobutanopyrro-
lines, imidazopyridines, pyridothienopyridazines, pyrimido-
thienopyridazines, and so on.2–5 To the best of our knowl-
edge, the only general approach toward linear 2-aza-1,3,5-
trienes is based on the reaction of lithiated allenes or
alkynes with aliphatic isothiocyanates (via a one-pot syn-
thesis and sigmatropic rearrangement of 1-aza-1,3,4-
trienes).2a,f,4,5
R2
R2
R3
1
Δ
3
+
OR1
OR1
SR4
SR4
Δ
R3
R2
R3
N
N
t-BuOK
DMSO–THF
ca. –30 °C
30 min
4
R2
2
OR1
OR1
SR4
+
N
R1 = alkyl, EtOCH(Me), FcCH2;
R2R3CH = alkyl, cyclo-alkyl, etc.
R4 = alkyl
N
R3
R3
6
5
Scheme 1 Our previous studies: synthesis and easy structural
reorganization of (alkylsulfanyl)-substituted 1-aza-1,3,4-trienes 1 into
2-aza-1,3,5-trienes 2, pyrroles 3, 5-alkoxy-6-(alkylsulfanyl)-2,3-dihydro-
pyridines 4, 3-alkoxy-2-(alkylsulfanyl)-4,5-dihydro-3H-azepines 5 and 6-
alkoxy-3H-azepines 6
In our previous studies, we reported the reaction of -
lithiated alkoxyallenes with aliphatic isothiocyanates fol-
lowed by S-alkylation of the adducts leading to alkyl buta-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

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N. A. Nedolya et al.
Paper
Synthesis
Very recently, a facile approach toward the synthesis of
new families of 4,5-dihydro-1,3-thiazoles via base-induced
structural rearrangements of linear 2-aza-1,3,5-trienic sys-
tems was reported.8 Thus, when (prop-2-ynylsulfanyl)-sub-
stituted 2-aza-1,3,5-trienes 7 (prepared in one preparative
step from lithiated alkoxyallenes, alkyl or cycloalkyl iso-
thiocyanates, and propargyl bromide) are involved in the
reaction with t-BuOK under conditions that are typical for
dihydroazepine/azepine synthesis,7 instead of the expected
4,5-dihydro-3H-azepines 5 (R4 = CH2C≡CH) and/or 3H-aze-
pines 6 (Scheme 1), previously unknown 2-(1-alkoxyprop-
1-enyl)-5-ethenylidene-4,5-dihydro-1,3-thiazoles 8 are ob-
tained (Scheme 2).8c
One-pot:
1. n-BuLi, THF–hexane
2. MeOCH2N=C=S
3. HC CCH2Br
OMe
N
OR
•
S
OMe
OR
9a–e
[1,5]-H shift
N
H
•
(1–3)
S
OR
13
R = Me (a), Et (b), n-Bu (c), EtOCH(Me) (d), FcCH2 (e)
Scheme 3 This work: one-pot synthesis of 2-aza-1,3,5-trienes 9
Their precursors, 1-aza-1,3,4-trienes 13, were not identi-
fied. Parallel formation of the corresponding pyrroles (cf.
Scheme 1) was also not observed. That is, after usual work-
up, 2-aza-1,3,5-trienes 9 were obtained as the only reaction
products (without special heating for isomerization of 1-
aza-1,3,4-trienes 13 into 2-aza-1,3,5-trienes 9).
One-Pot:
R3
1. n-BuLi
THF–hexane
OR1
R2
N
•
2. R2R3CHN=C=S
3. HC CCH2Br
4. Δ ([1,5]-H shift)
S
OR1
7
The lithiation of alkoxyallenes with n-BuLi in THF–
hexane is well documented5,6 and occurs at –60 to –40 °C in
5–10 minutes. The next stage, i.e., addition of the lithiated
alkoxyallene to methoxymethyl isothiocyanate is also an
easy process, which is realized at –60 to –40 °C over 10–15
minutes. Finally, S-propargylation of the formed adduct
was carried out at ca. –5 to 20 °C for 45–60 minutes.
It should be noted that (alkylsulfanyl)-substituted ana-
logues of 2-aza-1,3,5-trienes 9, prepared in a similar man-
ner, readily cyclize into 5-alkoxy-6-(alkylsulfanyl)-2-me-
thoxy-2,3-dihydropyridines, which, in turn, easily undergo
acid- or base-induced aromatization with elimination of
methanol to give 3-alkoxy-2-(alkylsulfanyl)pyridines.11
2-Aza-1,3,5-trienes 9 (as Z-isomers) were used in the
thiazole synthesis without further purification. Their reac-
tion with potassium tert-butoxide (1.0–1.1 equiv) resulting
in the formation of 2-(1-alkoxyprop-1-enyl)-5-ethynyl-1,3-
thiazoles 11 was carried out under conditions that are typi-
cal for the syntheses of 3H-azepines7 and 4,5-dihydro-1,3-
thiazoles,8 i.e., in DMSO–THF (ca. 1:5) at –35 to –30 °C for
30 minutes (Method A). The target products, i.e., 5-ethynyl-
2-vinyl-1,3-thiazoles 11, were obtained in yields of 56–67%
(after rough purification; practically pure by NMR spectro-
scopic analysis) (Table 1, entries 1–4) and 22–46% (after
double purification) as mixtures of Z- and E-isomers with
predominance of the Z-isomer. The content of the E-isomer
did not exceed 5–11% (Table 1) and was not identified for
1,3-thiazole 11e.
R3
t-BuOK
DMSO–THF
R2
•
N
OR1
ca. –30 °C
30 min
S
Me
8
R1 = alkyl, EtOCH(Me), FcCH2; R2R3CH = alkyl, cyclo-alkyl
Scheme 2 Previous reports: synthesis and easy structural reorganiza-
tion of (propargylsulfanyl)-substituted 2-aza-1,3,5-trienes 7 into 2-(1-
alkoxyprop-1-enyl)-5-ethenylidene-4,5-dihydro-1,3-thiazoles 8
We envisaged that the use of methyl N-[2-alkoxy-1-
(prop-2-ynylsulfanyl)buta-1,3-dienyl]iminoformates or
methyl N-[2-alkoxy-1-(allylsulfanyl)buta-1,3-dienyl]imino-
formates (2-aza-1,3,5-trienes 9 and 10), which can be easily
prepared from lithiated alkoxyallenes, methoxymethyl iso-
thiocyanate, and propargyl or allyl bromide, respectively, in
reactions with t-BuOK in DMSO–THF may lead to a new
class of functionally substituted 1,3-thiazoles, namely 2-(1-
alkoxyprop-1-enyl)-5-ethynyl-1,3-thiazoles 11 (see Table
1) and 2-(1-alkoxyprop-1-enyl)-5-vinyl-1,3-thiazoles 12
(Table 2). Indeed, these experiments met with our expecta-
tions.
A few representatives of 5-alkynyl- and 5-alkenyl-1,3-
thiazoles were obtained by palladium-catalyzed reactions
of terminal alkynes and alkenes with 1,3-thiazolyl halides9
or triflates10 (mainly under harsh conditions).
First, we successfully synthesized the previously un-
known 2-aza-1,3,5-trienes 9 in good to excellent yields
(71–100%) via gram-scale, one-pot reactions (Scheme 3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

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N. A. Nedolya et al.
Paper
Synthesis
Table 1 Proposed Synthetic Strategy to 5-Ethynyl-2-vinyl-1,3-thiazoles 11 and a Plausible Reaction Mechanism
OMe
t-BuOM (M = Na, K)
DMSO–THF
H2O
N
N
OR
–35 to –30 °C, 30 min
S
S
t-BuOM
OR
Me
11a–e
9a–e
OMe
N
MeO
MeO
MeO
M
N
N
N
a
OR
OR
OR
S
S
S
S
OR
A
C
B
D
– MeOH
b
– MeOH
– MeOH
N
N
N
OR
OR
OR
S
S
S
C'
E
B'
Entry
Substrate
Yield (%)a
Base
Product
Z/E ratio
Yield (%)b,c
OMe
N
N
OMe
Me
S
1
2
3
100
t-BuOK
ca. 95:5
ca. 100:0
ca. 92:8
46 (61)
S
OMe
11a
9a
t-BuONa
t-BuOK
35 (58)d
OMe
N
N
OEt
Me
32 (49)
(67)e
S
96
98
S
OEt
11b
11c
9b
9c
OMe
N
N
O-n-Bu
S
4
5
t-BuOK
t-BuOK
ca. 89:11
ca. 89:11
38 (56)
S
Me
O-n-Bu
OMe
N
N
OEt
O
S
S
90
22
Me
Me
O
OEt
11d
Me
9d
OMe
N
Fe
S
O
N
6
100
t-BuOK
ca. 100:0
36
O
S
Me
Fe
11e
9e
a Yield of crude product.
b Yield of purified product (based on the corresponding 2-aza-1,3,5-triene 9 used in the reaction).
c Yield in parentheses is that of thiazole 11 after rough purification.
d A mixture with ca. 20% of a compound of unidentified structure.
e Crude product, practically pure by NMR spectroscopic analysis.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

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N. A. Nedolya et al.
Paper
Synthesis
Based on our observations, a plausible mechanism for
the present t-BuOM-assisted reaction using (prop-2-ynyl-
sulfanyl)-substituted 2-aza-1,3,5-trienes 9 as the substrates
and direct precursors of 1,3-thiazoles 11 is shown in Table
1. The reaction is probably initiated by deprotonation of the
2-aza-1,3,5-triene 9 on the SCH2 moiety activated by the
ethynyl group. Next, a facile intramolecular cyclization of
intermediate A affords five-membered intermediate B. Mi-
gration of the negative charge (route a) provides intermedi-
ates C and D. The latter then undergoes elimination of
methanol followed by protonation of intermediate E to give
5-ethynyl-2-vinyl-1,3-thiazole 11. An alternative reaction
pathway (route b) suggests that intermediate B first elimi-
nates methanol and then isomerizes. In principle, any se-
quence of reactions involving the elimination of methanol
and isomerization with the participation of intermediates
A–E, B′ and C′ is possible here.
Unlike the 2-aza-1,3,5-trienes 7 depicted in Scheme 2,
the formation of 5-ethenylidene-2-vinyl-4,5-dihydro-1,3-
thiazoles 14 was not observed (Scheme 4). This means that
the elimination of methanol from intermediates B–D is
much faster than their acetylene–allene isomerization. In-
directly, this result indicates a greater probability of imple-
menting route b (Table 1).
A similar effect of the deprotonating base on the isomer
ratio was observed earlier in the synthesis of 2-(1-alkoxy-
prop-1-enyl)-5-ethenylidene-4,5-dihydro-1,3-thiazoles
8
via t-BuOM-assisted structural reorganization of (propar-
gylsulfanyl)-substituted 2-aza-1,3,5-trienes 7 (Scheme 2).8c
In this case also, mixtures of Z- and E-isomers were ob-
tained with t-BuOK, with a predominance of the Z-isomer,
but with t-BuONa only Z-isomers were observed.
The influence of the deprotonation conditions on the
yields of the products of the reactions between (propargyl-
sulfanyl)-2-aza-1,3,5-trienes and t-BuOM (M = Na, K) was
not studied in this work. However, this was accomplished
earlier in the transformations of azatrienes 7 into 4,5-dihy-
dro-1,3-thiazoles 8.8c It was found that despite the wide
variation in the reaction conditions (solvent, base, tempera-
ture, reaction time, and other options), the yields of the tar-
get products did not increase and amounted to 5–58%.
From the comparison of the yields of 1,3-thiazoles 11,
the crude products (pure by NMR spectroscopic analysis)
and those purified, it is evident that significant product
losses occur during purification by column chromatogra-
phy, possibly, as a result of their polymerization or decom-
position. Therefore, future efforts should be directed to-
ward finding suitable methods for the isolation and purifi-
cation of these products.
Our further investigations were focused on the one-pot
synthesis of methyl N-[(1Z)-1-(allylsulfanyl)-2-methoxybu-
ta-1,3-dienyl]iminoformates (2-aza-1,3,5-trienes 10) (from
lithiated alkoxyallenes, methoxymethyl isothiocyanate, and
allyl bromide), and their transformation into 2,5-divinyl-
4,5-dihydro-1,3-thiazoles 12 using the t-BuOK–DMSO–THF
system (Table 2).
OMe
t-BuOK
DMSO–THF
MeO
•
N
N
X
OR
–35 to –30 °C
30 min
S
S
Me
OR
14
9
Scheme 4 An alternative formally possible but not realized direction of
the reaction of 2-aza-1,3,5-trienes 9 with the t-BuOK–DMSO system
As with (propargylsulfanyl)-substituted analogues 9,
the 2-aza-1,3,5-trienes 10 were obtained in high yields un-
der similar conditions and were used without purification
in the synthesis of 2,5-divinyl-1,3-thiazoles 12. The re-
placement of propargyl bromide by allyl bromide did not
require modification of the reaction conditions for either
the synthesis of 2-aza-1,3,5-trienes 10 or for their transfor-
mation into 1,3-thiazoles 12. Unfortunately, the yields of
the latter were still moderate in this case, being 16–44% af-
ter double purification.
The only product obtained exclusively in the Z form was
1,3-thiazole 12a (Table 2, entry 1). The ratio of Z/E-isomers
for compounds 12b–e was ca. 90:10 to ca. 83:17 (by 1H
NMR spectroscopic analysis). For the 5-ethynyl-2-vinyl-1,3-
thiazole analogues 11, this interval was narrower: ca. 95:5
to ca. 89:11. Moreover, in both cases, the largest content of
the E-isomer (11–17%) was observed for thiazoles 11c and
12c derived from butoxyallene.
When 2-aza-1,3,5-triene 9a was treated with the t-
BuONa–DMSO system (Method B), only the Z-isomer of 1,3-
thiazole 11a was formed, albeit in a mixture with a new
compound of unidentified structure in a ratio of ca. 80:20
(by 1H NMR spectroscopic analysis) (Table 1, entry 2).
The exclusive Z configuration of the 1,3-thiazole 11a ob-
tained in the presence of t-BuONa is likely due to the forma-
tion of a more stable (than with a bulkier potassium coun-
terion) intermediate (D′ or E′) (Figure 1), wherein the sodi-
um cation is coordinated both to a terminal carbanion
center and a lone pair of electrons of the oxygen atom (from
the methoxy group), thereby fixing the Z configuration.
MeO
N
N
or
CH2
Na
CH2
Na
S
S
O:
O:
Me
Me
D'
E'
The plausible mechanism for the transformation of 2-
aza-1,3,5-trienes 10 into thiazoles 12 is similar to that de-
picted in Table 1.
Figure 1 A possible intermediate fixing the Z configuration of thiazole
11a
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

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N. A. Nedolya et al.
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Synthesis
Table 2 Proposed Two-Step Approach to 2,5-Divinyl-1,3-thiazoles 12 [via One-Pot Synthesis and Structural Reorganization of (Allylsulfanyl)-Substitut-
ed 2-Aza-1,3,5-trienes 10]
OMe
t-BuOK (ca. 1.0–1.2 equiv)
1. n-BuLi, THF–hexane
N
N
DMSO–THF
OR
OR
•
S
–35 to –30 °C, 30 min
S
2. MeOCH2N=C=S
3. CH2=CHCH2Br
[–80 °C to rt, 45–60 min]
OR
Me
12a–e
16–44%
Z/E = ca. 100:0-83:17
10a–e
76–100%
one-pot
R = Me (a), Et (b), n-Bu (c), EtOCH(Me) (d), FcCH2 (e)
Entry
1
Substrate
Yield (%)a
Base
Product
Z/E ratio
Yield (%)b,c
18 (63)
OMe
N
N
N
N
OMe
Me
S
76
t-BuOK
ca. 100:0
ca. 88:12
ca. 83:17
S
OMe
12a
12b
10a
10b
10c
OMe
N
OEt
Me
S
2
3
94
91
t-BuOK
t-BuOK
34 (68)
44 (58)
S
OEt
OMe
N
O-n-Bu
S
S
Me
O-n-Bu
12c
OMe
N
N
OEt
O
S
S
4
93
t-BuOK
ca. 90:10
16 (73)
Me
Me
O
OEt
12d
Me
10d
OMe
N
Fe
S
O
N
5
100
t-BuOK
ca. 90:10
43 (64)
O
S
Me
Fe
12e
10e
a Yield of crude product.
b Yield of purified product (based on the corresponding 2-aza-1,3,5-triene 10 used in the reaction).
c Yield in parentheses is that of thiazole 12 after rough purification.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

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N. A. Nedolya et al.
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Synthesis
The efficiency of readily available 2-aza-1,3,5-trienes 9
and 10 as direct precursors of new classes of functionally
substituted 1,3-thiazoles was confirmed by the successful
synthesis of 10 representative examples of previously un-
known 5-ethynyl-2-vinyl-1,3-thiazoles 11 and 2,5-divinyl-
1,3-thiazoles 12. Although the yields of thiazoles 11 and 12
are moderate, there are no other approaches or methods
available for the synthesis of such compounds, which are
promising for pharmacology, organic synthesis, and materi-
als science.
In conclusion, the reported reaction involving mild
deprotonation of propargylsulfanyl and allylsulfanyl sub-
stituents in 2-aza-1,3,5-trienes {methyl N-[2-alkoxy-1-
(prop-2-ynylsulfanyl)buta-1,3-dienyl]- and methyl N-[1-
(allylsulfanyl)-2-alkoxybuta-1,3-dienyl]iminoformates},
which are readily available from lithiated alkoxyallenes,
methoxymethyl isothiocyanate and propargyl or allyl bro-
mide, with t-BuOK or t-BuONa in DMSO–THF not only sig-
nificantly broadens knowledge about the metalation reac-
tions of azatrienic systems having several base-sensitive re-
action centers, but can also serve as the basis for a novel
approach to the simple synthesis of new classes of multi-
functional 1,3-thiazoles, known representatives of which
are used widely in medicine and pharmacology.12
methoxymethyl isothiocyanate (15–50 mmol) in THF (3–5 mL) was
added in one portion. The mixture was stirred for 10–15 min at –60
to –35 °C, cooled to ca. –80 °C and propargyl bromide (25–55 mmol)
or allyl bromide (25–35 mmol) was added in one portion, after which
the cooling bath was removed. After stirring mainly at –5 to 5 °C for
45–60 min, the mixture was cooled to ca. –40 °C and then treated
with sat. aq NH4Cl (20–40 mL). The layers were separated and the
products were extracted from the aq fraction with Et2O (3 × 30 mL).
The combined organic extracts were washed with H2O (2 × 40 mL),
dried (MgSO4) and concentrated under reduced pressure (on a rotary
evaporator) to give a residue consisting of the corresponding 2-aza-
1,3,5-triene 9 or 10 (by 1H NMR spectroscopic analysis). The yields
(based on isothiocyanate) and analytical data of the 2-aza-1,3,5-
trienes 9 and 10 are reported below. For the syntheses of thiazoles 11
and 12, crude 2-aza-1,3,5-trienes 9 and 10 were used because it was
impossible to purify the compounds via standard practices [during
vacuum distillation they cyclize to give 2,3-dihydropyridines 4 (R2
=
H, R3 = OMe) (Scheme 1),11 and upon chromatographic separation
they decomposed]. For this reason, elemental analysis was not per-
formed on these compounds.
1,3-Thiazoles 11 and 12; General Procedure
To a stirred solution of the crude 2-aza-1,3,5-triene 9 (15–50 mmol)
or 10 (15–23 mmol) in anhyd THF (22–75 mL) were successively add-
ed anhyd DMSO (5–15 mL) and t-BuOK (15–25 mmol) (Method A) or
t-BuONa (54 mmol) (Method B) at –60 °C. The mixture was stirred for
30 min while the temperature was kept between –35 and –30 °C,
cooled to ca. –60 °C and then H2O (20–30 mL) was added. After sepa-
ration of the layers, the products were extracted from the aq fraction
with Et2O (4 × 30–40 mL). The combined organic extracts were
washed with H2O (3 × 50 mL) and dried (MgSO4). Flash column chro-
matography of the solution on neutral alumina (2.5 cm layer) fol-
lowed by concentration under reduced pressure (on a rotary evapora-
tor) gave the crude product, which was purified by column chroma-
tography on neutral alumina (eluents: hexane, hexane–Et2O, 10:1,
3:1, 1:1) to give the 1,3-thiazole 11 or 12.
Methoxymethyl isothiocyanate was prepared by boiling chloro(me-
thoxy)methane with KSCN in pentane.13 The alkoxyallenes were syn-
thesized according to reported procedures.14 n-BuLi (2.5 M solution in
hexane) and other reagents and solvents were commercially avail-
able. All solvents were purified according to standard procedures. All
reactions were carried out by employing anhydrous conditions under
an argon atmosphere (with n-BuLi). For the reactions at low tempera-
tures, a cooling bath with liquid nitrogen was used. Reaction courses
and product mixtures were routinely monitored by TLC using Merck
precoated silica gel 60 F254 aluminum plates and visualized by expo-
sure to I2 vapor. Flash column chromatography was performed using
neutral alumina (0.1–0.2 nm). Melting points were determined using
a SGW X-4 melting point apparatus fitted with a microscope. IR spec-
tra were recorded neat or as a film from Et2O on a Bruker Vertex-70 IR
spectrophotometer. 1H (400.13 MHz), 13C (100.62 MHz) and 15N
(40.55 MHz) NMR spectra were recorded on Bruker DPX-400 and
Bruker AV-400 spectrometers in CDCl3 at room temperature. Chemi-
cal shifts () are quoted in ppm to the nearest 0.01 ppm (for 1H) and
0.1 ppm (for 13C and 15N), and are referenced to HMDS (for 1H), CDCl3
(for 13C) and MeNO2 (for 15N) as internal standards. Coupling con-
stants (J) are reported in hertz (Hz) to the nearest 0.1 Hz. Standard
abbreviations are used to designate the splitting patterns. Assign-
ments of spectra were carried out using 2D NMR experiments. Mass
spectra (electron impact, 70 eV) were obtained on a Shimadzu GCMS-
QP5050A instrument. Microanalyses were performed on a Flash EA
1112 Series elemental analyzer.
Methyl N-[(1Z)-2-Methoxy-1-(prop-2-ynylsulfanyl)buta-1,3-die-
nyl]iminoformate (9a)
The general experimental procedure was followed using THF (50 mL),
n-BuLi (23 mL, 2.5 M in hexane, 57.5 mmol), methoxyallene (6.00 g,
85.6 mmol): –60 to –55 °C, 10 min; MeOCH2NCS (5.16 g, 50.0 mmol)
/THF (3 mL): –60 to –45 °C, 10 min; BrCH2C≡CH (6.54 g, 55.0 mmol): –
75 → –5 to 5 °C, 45 min. The title compound 9a was obtained as a
dark-brown liquid in a yield of ca. 100% (10.60 g).
IR (neat): 3292 (HC≡), 2118 (C≡C), 1630 (C=C), 1560 (C=N) cm–1
.
3
1H NMR (400 MHz, CDCl3):  = 8.04 (s, 1 H, N=CH), 6.77 (dd, Jtrans
=
=
3
3
17.4 Hz, Jcis = 11.0 Hz, 1 H, CH2=СН), 5.44 and 5.14 (both dd, Jtrans
3
2
17.4 Hz, Jcis = 11.0 Hz, Jgem = 1.8 Hz, 2 H, CH2=СН), 3.83 (s, 3 H,
N=CНOCH3), 3.69 (s, 3 H, OCH3), 3.40 (d, 4J = 2.6 Hz, 2 H, SCH2), 2.22 (t,
4J = 2.6 Hz, 1 H, HC≡).
13C NMR (100 MHz, CDCl3):  = 157.2 (N=CH), 151.2 (OC=), 128.7
(SC=), 127.4 (CH2=СН), 114.0 (CH2=СН), 80.2 (C≡), 71.4 (HC≡), 59.8
(OCH3), 53.9 (N=CНOCH3), 20.3 (SCH2).
5-Ethynyl-2-(1-methoxyprop-1-enyl)-1,3-thiazole (11a)
2-Aza-1,3,5-trienes 9 and 10; General Procedure
Following the general procedure (Method A), 1,3-thiazole 11a [as a
mixture of Z- and E-isomers in a ratio of ca. 95:5 (estimated by 1H
NMR spectroscopic analysis)] was obtained from 2-aza-1,3,5-triene
9a (4.43 g, 21.0 mmol) and t-BuOK (2.58 g, 23.0 mmol) in THF (31 mL)
and DMSO (6 mL) in a yield of 61% (2.30 g, practically pure by NMR
To a vigorously stirred solution of the alkoxyallene (15–86 mmol) in
anhyd THF (20–50 mL) was added n-BuLi (15–58 mmol, 6.5–23 mL) at
–95 °C under argon. After stirring for an additional 5–10 min at ca.
–60 to –35 °C, the solution was cooled to –90 °C and a mixture of
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

G
N. A. Nedolya et al.
Paper
Synthesis
spectroscopic analysis), after rough purification on neutral alumina.
Further separation (neutral alumina, hexane–Et2O, 1:1) gave com-
pound 11a as a mixture of Z- and E-isomers in a ratio of ca. 93:7 (1.72
g, 46%); brownish mobile liquid.
15N NMR (40 MHz, CDCl3):  = –137.0.
2-(1-Ethoxyprop-1-enyl)-5-ethynyl-1,3-thiazole (11b)
Following the general procedure (Method A), 1,3-thiazole 11b [as a
mixture of Z- and E-isomers in a ratio of ca. 92:8 (by 1H NMR spectro-
scopic analysis)] was obtained from 2-aza-1,3,5-triene 9b (3.98 g,
17.7 mmol) and t-BuOK (2.19 g, 19.6 mmol) in THF (27 mL) and
DMSO (5 mL) in a yield of 67% (2.28 g, practically pure by NMR spec-
troscopic analysis) and 49% (1.66 g) after rough purification on neu-
tral alumina). Further separation (neutral alumina, hexane) gave
compound 11b as the Z-isomer (0.21 g, 6%; yellow mobile liquid; nD
1.5798) and as a mixture of Z- and E-isomers in a ratio of ca. 89:11
(0.88 g, 26%; orange mobile liquid).
Following the general procedure (Method B), 1,3-thiazole 11a (Z-iso-
mer) in a mixture with a new compound of an unidentified structure
in a ratio of ca. 80:20 (by 1H NMR spectroscopic analysis) was ob-
tained from 2-aza-1,3,5-triene 9a (10.50 g, 49.8 mmol) and t-BuONa
(5.19 g, 54.1 mmol) in THF (75 mL) and DMSO (15 mL) in a yield of
58% (5.14 g, practically pure by NMR spectroscopic analysis), after
rough purification on neutral alumina. Further purification (neutral
alumina, hexane, hexane–Et2O, 10:1) gave compound 11a (3.12 g,
35%) as a brownish mobile liquid. The new product, of the same mo-
lecular weight as thiazole 11a [MS (EI, 70 eV): m/z (%) = 179 (23) [M]+,
178 (100), 164 (80)], was not isolated in individual form.
23
Z-Isomer of 1,3-Thiazole 11b
IR (neat): 3296 (HC≡), 3084, 3051, 2979, 2931, 2916, 2895, 2881,
2858, 2105 (C≡C), 1646, 1498, 1478, 1442, 1427, 1390, 1377, 1307,
1244, 1195, 1153, 1121, 1107, 1089, 1055, 1009, 965, 933, 866, 826,
Z-Isomer of 1,3-Thiazole 11a
IR (neat): 3293 (HC≡), 3087, 2989, 2938, 2916, 2855, 2836, 2106 (C≡C),
761, 681, 665, 594, 553, 534, 477, 444, 422 cm–1
.
1647, 1498, 1442, 1419, 1378, 1306, 1245, 1184, 1151, 1122, 1058,
961, 933, 915, 865, 828, 760, 732, 670, 598, 536, 473, 424 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.83 (s, 1 H, 4-CH=), 6.19 (q, 3J = 7.2 Hz,
1 H, CH3CH=), 3.92 (q, 3J = 7.1 Hz, 2 H, OCH2CH3), 3.47 (s, 1 H, HC≡),
1.82 (d, 3J = 7.2 Hz, 3 H, CH3CH=), 1.35 (t, 3J = 7.1 Hz, 3 H, OCH2CH3).
The 1H–1H NOESY 2D experiment provided additional support for the
proposed structure.
13C NMR (100 MHz, CDCl3):  = 167.4 (C=N), 148.7 (4-CH=), 148.5
(OC=), 116.9 (5-C), 114.6 (CH3CH=), 84.7 (HC≡), 73.8 (C≡), 68.6
(OCH2CH3), 15.6 (OCH2CH3), 11.4 (CH3CH=).
1H NMR (400 MHz, CDCl3):  = 7.84 (s, 1 H, 4-CH=), 6.17 (q, 3J = 7.3 Hz,
1 H, CH3CH=), 3.74 (s, 3 H, OCH3), 3.51 (s, 1 H, HC≡), 1.83 (d, 3J = 7.3
Hz, 3 H, CH3CH=).
13C NMR (100 MHz, CDCl3):  = 166.5 (C=N), 149.5 (OC=), 148.7 (4-
CH=), 117.6 (5-C), 114.2 (CH3CH=), 84.8 (HC≡), 73.6 (C≡), 60.2 (OCH3),
11.0 (CH3CH=).
The 1H–13C HMBC and 1H–13C HSQC 2D experiments provided addi-
tional support for the proposed structure.
15N NMR (40 MHz, CDCl3):  = –73.1.
Anal. Calcd for C9H9NOS (179.2): C, 60.31; H, 5.06; N, 7.81; S, 17.89.
Found: С, 60.48; Н, 5.00; N, 7.70; S, 17.81.
Anal. Calcd for C10H11NOS (193.3): C, 62.15; H, 5.74; N, 7.25; S, 16.59.
Found: C, 62.10; H, 5.69; N, 7.23; S, 16.56.
E-Isomer of 1,3-Thiazole 11a (Tentative Assignment)
E-Isomer of 1,3-Thiazole 11b (Tentative Assignment)
1H NMR (400 MHz, CDCl3):  = 7.92 (s, 1 H, 4-CH=), 5.18 (q, 3J = 7.5 Hz,
1 H, CH3CH=), 3.68 (s, 3 H, OCH3), 3.35 (s, 1 H, HС≡), 2.14 (d, 3J = 7.5
Hz, 3 H, CH3CH=).
13C NMR (100 MHz, CDCl3):  = 155.8 (C=N), 149.8 (OC=), 148.0 (4-
CH=), 125.2 (5-C), 101.8 (CH3CH=), 83.8 (HC≡), 73.6 (C≡), 55.6 (OCH3),
12.2 (CH3CH=).
1H NMR (400 MHz, CDCl3):  = 7.92 (s, 1 H, 4-CH=), 5.18 (q, 3J = 7.5 Hz,
1 H, CH3CH=), 3.85 (q, 3J = 7.0 Hz, 2 H, OCH2CH3), 3.46 (s, 1 H, HC≡),
2.13 (d, 3J = 7.5 Hz, 3 H, CH3CH=), 1.36 (t, 3J = 7.0 Hz, 3 H, OCH2CH3).
The 1H–1H NOESY 2D experiment provided additional support for the
proposed structure.
13C NMR (100 MHz, CDCl3):  = 167.4 (C=N), 148.7 (4-CH=), 148.2
(OC=), 116.8 (5-C), 103.1 (CH3CH=), 84.7 (HC≡), 73.9 (C≡), 64.3
(OCH2CH3), 14.7 (OCH2CH3), 12.4 (CH3CH=).
Methyl N-[(1Z)-2-Ethoxy-1-(prop-2-ynylsulfanyl)buta-1,3-dienyl]
iminoformate (9b)
15N NMR (40 MHz, CDCl3):  = –63.2.
The general experimental procedure was followed using THF (25 mL),
n-BuLi (12 mL, 2.5 M in hexane, 29.0 mmol), ethoxyallene (4.00 g,
48.0 mmol): –55 to –40 °C, 6 min; MeOCH2NCS (2.58 g, 25.0 mmol)/
THF (3 mL): –55 to –45 °C, 15 min; BrCH2C≡CH (3.71 g, 31.0 mmol):
–80 → –5 to 5 °C, 45 min. The title compound 9b was obtained as a
brown mobile liquid in a yield of 96% (5.42 g).
Methyl N-[(1Z)-2-Butoxy-1-(prop-2-ynylsulfanyl)buta-1,3-dienyl]
iminoformate (9c)
The general experimental procedure was followed using THF (25 mL),
n-BuLi (12 mL, 2.5 M in hexane, 29.0 mmol), n-butoxyallene (3.37 g,
30.0 mmol): –49 to –45 °C, 7 min; MeOCH2NCS (2.58 g, 25.0 mmol)/
THF (3 mL): –45 to –40 °C, 15 min; BrCH2C≡CH (3.80 g, 32.0 mmol):
–80 → 15 to 20 °C, 1 h. The title compound 9c was obtained as a dark-
brown mobile liquid in a yield of 98% (6.21 g).
IR (neat): 3293 (HC≡), 2118 (C≡C), 1632 (C=C), 1556 (C=N) cm–1
.
3
1H NMR (400 MHz, CDCl3):  = 8.03 (s, 1 H, N=CH), 6.80 (dd, Jtrans
=
=
3
3
17.4 Hz, Jcis = 10.9 Hz, 1 H, CH2=СН), 5.43 and 5.11 (both dd, Jtrans
17.4 Hz, 3Jcis = 10.9 Hz, 2Jgem = 1.9 Hz, 2 H, CH2=СН), 3.88 (q, 3J = 7.1 Hz,
2 H, OCH2CH3), 3.83 (s, 3 H, N=CHOCH3), 3.41 (d, 4J = 2.6 Hz, 2 H, SCH2)
, 2.21 (t, 4J = 2.6 Hz, 1 H, HC≡), 1.35 (t, 3J = 7.1 Hz, 3 H, OCH2CH3).
IR (neat): 3297 (HC≡), 2116 (C≡C), 1633 (C=C), 1559 (C=N) cm–1
.
3
1H NMR (400 MHz, CDCl3):  = 8.04 (s, 1 H, N=CH), 6.79 (dd, Jtrans
=
=
3
3
17.4 Hz, Jcis = 10.8 Hz, 1 H, CH2=СН), 5.43 and 5.11 (both dd, Jtrans
13C NMR (100 MHz, CDCl3):  = 157.0 (N=CH), 150.0 (OC=), 128.7
(SC=), 127.8 (CH2=СН), 113.6 (CH2=СН), 80.2 (C≡), 71.3 (HC≡), 68.0
(OCH2CH3), 53.8 (N=CHOCH3), 20.1 (SCH2), 15.5 (OCH2CH3).
The 1H–13C HMBC and 1H–13C HSQC 2D experiments provided addi-
tional support for the proposed structure.
3
2
17.4 Hz, Jcis = 10.8 Hz, Jgem = 1.8 Hz, 2 H, CH2=СН), 3.82 (s, 3 H,
N=CHOCH3), 3.81 (t, 3J = 6.6 Hz, 2 H, OCH2C3H7), 3.41 (d, 4J = 2.5 Hz, 2
H, SCH2), 2.19 (t, 4J = 2.5 Hz, 1 H, HC≡), 1.76–1.69 (m, 2 H,
OCH2CH2C2H5), 1.53–1.44 [m, 2 H, O(CH2)2CH2CH3], 0.95 [t, 3J = 7.4 Hz,
3 H, O(CH2)3CH3].
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

H
N. A. Nedolya et al.
Paper
Synthesis
13C NMR (100 MHz, CDCl3):  = 157.0 (N=CH), 150.2 (OC=), 128.8
(SC=), 127.9 (CH2=СН), 113.6 (CH2=СН), 80.3 (C≡), 72.2 (OCH2C3H7),
71.2 (HC≡), 53.9 (N=CHOCH3), 32.2 (OCH2CH2C2H5), 20.3 (SCH2), 19.2
[O(CH2)2CH2CH3], 13.9 [O(CH2)3CH3].
The 1H–13C HMBC and 1H–13C HSQC 2D experiments provided addi-
tional support for the proposed structure.
Methyl N-[(1Z)-2-(1-Ethoxyethoxy)-1-(prop-2-ynylsulfanyl)buta-
1,3-dienyl]iminoformate (9d)
The general experimental procedure was followed using THF (20 mL),
n-BuLi (8.5 mL, 2.5 M in hexane, 21.2 mmol), 1-(1-ethoxyethoxy)-
allene (2.69 g, 21.0 mmol): –58 to –52 °C, 10 min; MeOCH2NCS (2.06
g, 20.0 mmol)/THF (3 mL): –45 to –40 °C, 12 min; BrCH2C≡CH (3.00 g,
25.2 mmol): –80 → 5 °C, 45 min. The title compound 9d was obtained
as a dark-brown viscous liquid in a yield of 90% (4.83 g).
2-(1-Butoxyprop-1-enyl)-5-ethynyl-1,3-thiazole (11c)
IR (neat): 3291 (HC≡), 2118 (C≡C), 1632 (C=C), 1568 (C=N) cm–1
.
Following the general procedure (Method A), 1,3-thiazole 11c [as a
mixture of Z- and E-isomers in a ratio of ca. 89:11 (by 1H NMR spec-
troscopic analysis)] was obtained from 2-aza-1,3,5-triene 9c (6.15 g,
24.3 mmol) and t-BuOK (2.80 g, 25.0 mmol) in THF (31.5 mL) and
DMSO (6.5 mL) in a yield of 56% (3.00 g, practically pure by NMR spec-
troscopic analysis), after rough purification on neutral alumina. Fur-
ther separation (neutral alumina, hexane, hexane–Et2O, 10:1) gave
compound 11c as the Z-isomer [0.93 g (17%); oily, mobile amber
liquid; nD22 1.5640] and as a mixture of Z- and E-isomers in a ratio of
3
1H NMR (400 MHz, CDCl3):  = 8.03 (s, 1 H, N=CH), 6.88 (dd, Jtrans
=
=
3
3
17.1 Hz, Jcis = 11.0 Hz, 1 H, CH2=СН), 5.58 and 5.15 (both dd, Jtrans
17.1 Hz, 3Jcis = 11.0 Hz, 2Jgem = 2.0 Hz, 2 H, CH2=СН), 5.28 (q, 3J = 5.1 Hz,
1 H, OCHO), 3.84 (s, 3 H, N=CHOCH3), 3.84 and 3.61 (dq, 2J = 9.3 Hz,
3J = 7.1 Hz, 2 H, OCH2CH3), 3.41 and 3.37 (dd, 2J = 16.4 Hz, 4J = 2.5 Hz, 2
H, SCH2), 2.20 (t, 4J = 2.5 Hz, 1 H, HC≡), 1.46 [d, 3J = 5.1 Hz, 3 H,
OCH(CH3)O], 1.16 (t, 3J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (100 MHz, CDCl3):  = 157.1 (C=N), 148.5 (OC=), 129.4
(CH2=СН), 128.6 (SC=), 114.7 (CH2=СН), 103.1 (OCHO), 80.2 (C≡), 71.4
(HC≡), 64.4 (OCH2CH3), 54.0 (N=CHOCH3), 21.2 [OCH(CH3)O], 20.2
(SCH2), 15.4 (OCH2CH3).
22
ca. 79:21 [1.12 g (21%); oily, mobile yellow-orange liquid; nD
1.5511].
Z-Isomer of 1,3-Thiazole 11c
IR (film): 3298 (HC≡), 3083, 3048, 2957, 2931, 2871, 2105 (C≡C),
2-[1-(1-Ethoxyethoxy)prop-1-enyl]-5-ethynyl-1,3-thiazole (11d)
1645, 1549, 1496, 1453, 1432, 1380, 1308, 1244, 1153, 1125, 1065,
Following the general procedure (Method A), 1,3-thiazole 11d [as a
mixture of Z- and E-isomers in a ratio of ca. 89:11 (by 1H NMR spec-
troscopic analysis)] was obtained from 2-aza-1,3,5-triene 9d (4.75 g,
17.6 mmol) and t-BuOK (2.19 g, 19.6 mmol) in THF (27 mL) and
DMSO (5 mL) in a yield of 22% (0.93 g) after double purification (neu-
tral alumina, hexane); orange oily liquid.
1045, 955, 926, 865, 825, 760, 665, 595, 538, 469, 423 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.83 (s, 1 H, 4-CH=), 6.18 (q, 3J = 7.3 Hz,
1 H, CH3СН=), 3.85 (t, 3J = 7.0 Hz, 2 H, OCH2C3H7), 3.45 (s, 1 H, HC≡),
1.83 (d, 3J = 7.3 Hz, 3 H, CH3CH=), 1.76–1.69 (m, 2 H, OCH2CH2C2H5),
1.53–1.44 [m, 2 H, O(CH2)2CH2CH3], 0.96 [t, 3J = 7.1 Hz, 3 H, O(CH2)3CH3].
13C NMR (100 MHz, CDCl3):  = 167.4 (C=N), 148.7 (4-CH=), 148.0
(OC=), 116.9 (5-C), 114.2 (CH3CH=), 84.6 (HC≡), 73.8 (C≡), 72.8
(OCH2C3H7), 32.2 (OCH2CH2C2H5), 19.2 [O(CH2)2CH2CH3], 13.8 [O(CH2)3CH3],
11.3 (CH3CH=).
The 1H–13C HMBC and 1H–13C HSQC 2D experiments provided addi-
tional support for the proposed structure.
Z-Isomer of 1,3-Thiazole 11d
1H NMR (400 MHz, CDCl3):  = 7.82 (s, 1 H, 4-CH=), 6.17 (q, 3J = 7.1 Hz,
3
2
1 H, CH3CH=), 5.17 (q, J = 5.1 Hz, 1 H, OCHO), 3.80 and 3.57 (dq, J =
3
3
9.3 Hz, J = 7.1 Hz, 2 H, OCH2CH3), 3.48 (s, 1 H, HC≡), 1.87 (d, J = 7.1
Hz, 3 H, CH3CH=), 1.46 [d, 3J = 5.1 Hz, 3 H, OCH(CH3)O], 1.14 (t, 3J = 7.1
Hz, 3 H, OCH2CH3).
15N NMR (40 MHz, CDCl3):  = –64.3.
13C NMR (100 MHz, CDCl3):  = 167.4 (C=N), 148.3 (4-CH=), 146.3
(OC=), 117.0 (5-C), 115.9 (CH3CH=), 102.3 (OCHO), 84.6 (HC≡), 73.6
(C≡), 64.3 (OCH2CH3), 20.9 [OCH(CH3)O], 15.2 (OCH2CH3), 11.7
(CH3CH=).
Anal. Calcd for C12H15NOS (221.3): С, 65.12; Н, 6.83; N, 6.33; S, 14.49.
Found: С, 64.91; Н, 7.00; N, 6.21; S, 14.28.
E-Isomer of 1,3-Thiazole 11c (Tentative Assignment)
Anal. Calcd for C12H15NO2S (237.3): C, 60.73; H, 6.37; N, 5.90; S, 13.51.
Found: C, 60.57; H, 6.20; N, 5.73; S, 13.38.
IR (film) (Z- and E-isomers, ca. 79:21): 3298 (HC≡), 3084, 2957, 2933,
2871, 2105 (C≡C), 1644, 1567, 1499, 1457, 1428, 1380, 1308, 1242,
1154, 1120, 1069, 1047, 957, 927, 855, 826, 759, 665, 596, 539, 468
E-Isomer of 1,3-Thiazole 11d (Tentative Assignment)
cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.93 (s, 1 H, 4-CH=), 5.55 (q, 3J = 7.5 Hz,
1H NMR (400 MHz, CDCl3):  = 7.92 (s, 1 H, 4-CH=), 5.18 (q, 3J = 7.3 Hz,
1 H, CH3СН=), 3.80 (t, 3J = 7.0 Hz, 2 H, OCH2C3H7), 3.35 (s, 1 H, HC≡),
2.14 (d, 3J = 7.3 Hz, 3 H, CH3CH=), 1.76–1.69 (m, 2 H, OCH2CH2C2H5),
1.53–1.44 [m, 2 H, O(CH2)2CH2CH3], 0.96 [t, 3J = 7.1 Hz, 3 H, O(CH2)3CH3].
13C NMR (100 MHz, CDCl3):  = 165.6 (C=N), 148.2 (4-CH=), 147.1
(OC=), 116.8 (5-C), 114.2 (CH3CH=), 84.5 (HC≡), 74.6 (C≡), 68.4
(OCH2C3H7), 31.2 (OCH2CH2C2H5), 19.4 [O(CH2)2CH2CH3], 13.8
[O(CH2)3CH3], 11.3 (CH3CH=).
The 1H–13C HMBC and 1H–13C HSQC 2D experiments provided addi-
tional support for the proposed structure.
15N NMR (40 MHz, CDCl3):  = –74.6.
3
2
1 H, CH3CH=), 5.17 (q, J = 5.1 Hz, 1 H, OCHO), 3.80 and 3.56 (dq, J =
3
3
9.1 Hz, J = 7.1 Hz, 2 H, OCH2CH3), 3.35 (s, 1 H, HC≡), 2.15 (d, J = 7.5
Hz, 3 H, CH3CH=), 1.45 [d, 3J = 5.1 Hz, 3 H, OCH(CH3)O], 1.14 (t, 3J = 7.1
Hz, 3 H, OCH2CH3).
13C NMR (100 MHz, CDCl3):  = 167.4 (C=N), 148.4 (4-CH=), 146.3
(OC=), 116.9 (5-C), 115.9 (CH3CH=), 100.9 (OCHO), 84.7 (HC≡), 73.8
(C≡), 61.8 (OCH2CH3), 20.2 [OCH(CH3)O], 15.1 (OCH2CH3), 12.6
(CH3CH=).
Methyl N-[(1Z)-2-(Ferrocenylmethoxy)-1-(prop-2-ynylsulfanyl)-
1,3-butadienyl]iminoformate (9e)
The general experimental procedure was followed using THF (25 mL),
n-BuLi (6.5 mL, 2.5 M in hexane, 16.25 mmol), 1-(ferrocenylmethoxy)
allene (3.81 g, 15.0 mmol): –50 to –39 °C, 7 min; MeOCH2NCS (1.55 g,
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

I
N. A. Nedolya et al.
Paper
Synthesis
15.0 mmol)/THF (5 mL): –45 to –40 °C, 12 min; BrCH2C≡CH (3.20 g,
26.9 mmol): –80 → 5 °C, 1 h. The title compound 9e was obtained as a
very viscous dark-brown liquid in a yield of ca. 100% (5.92 g).
2-[(Z)-1-Methoxyprop-1-enyl]-5-vinyl-1,3-thiazole (12a)
Following the general procedure (Method A), thiazole 12a [Z-isomer
(by 1H NMR spectroscopic analysis)] was obtained from 2-aza-1,3,5-
triene 10a (4.80 g, 22.5 mmol) and t-BuOK (2.73 g, 24.3 mmol) in THF
(34 mL) and DMSO (7 mL) in a yield of 63% (2.58 g, practically pure by
NMR spectroscopic analysis), after rough purification on neutral alu-
mina. Further separation (neutral alumina, hexane, hexane–Et2O,
IR (neat): 3290 (HC≡), 2114 (C≡C), 1687, 1635 (C=C), 1514 (C=N) cm–1
.
3
1H NMR (400 MHz, CDCl3):  = 8.05 (s, 1 H, N=CH), 6.81 (dd, Jtrans
=
=
3
3
17.4 Hz, Jcis = 10.8 Hz, 1 H, CH2=СН), 5.45 and 5.13 (both dd, Jtrans
3
2
17.4 Hz, Jcis = 10.8 Hz, Jgem = 1.9 Hz, 2 H, CH2=СН), 4.65 (s, 2 H,
OCH2Fc), 4.22 (br s, 2 H, -H, Fc), 4.13 (br s, 7 H, -H, C5H5, Fc), 3.83 (s,
3 H, N=CHOCH3), 3.40 (d, 4J = 2.6 Hz, 2 H, SCH2), 2.20 (t, 4J = 2.6 Hz, 1
H, HC≡).
23
10:1) gave compound 12a (0.74 g, 18%); yellow mobile liquid; nD
1.5810.
IR (neat): 3088, 3034, 2998, 2979, 2937, 2918, 2854, 2837, 1743,
1718, 1674, 1646, 1621, 1586, 1565, 1507, 1444, 1403, 1377, 1305,
1268, 1245, 1221, 1192, 1149, 1122, 1091, 1060, 1029, 976, 962, 913,
13C NMR (100 MHz, CDCl3):  = 157.1 (N=CH), 149.9 (OC=), 129.1
(SC=), 127.8 (CH2=СН), 114.1 (CH2=СН), 82.6 (i-C, Fc), 80.3 (C≡), 71.3
(HC≡), 70.6 (OCH2Fc), 69.5 (-C, Fc), 68.5 (-C, Fc), 68.4 (C5H5, Fc), 54.0
(N=CHOCH3), 20.3 (SCH2).
858, 826, 761, 732, 677, 600, 481 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.56 (s, 1 H, 4-CH=), 6.76 (dd, Jtrans
=
3
17.5 Hz, 3Jcis = 10.9 Hz, 1 H, CH2=СН), 6.10 (q, 3J = 7.3 Hz, 1 H, CH3CH=)
3
3
, 5.50 and 5.22 (both d, Jtrans = 17.5 Hz, Jcis = 10.9 Hz, 2 H, CH2=СН),
3.75 (s, 3 H, OCH3), 1.83 (d, 3J = 7.3 Hz, 3 H, CH3CH=).
5-Ethynyl-2-[(Z)-1-(ferrocenylmethoxy)prop-1-enyl]-1,3-thiazole
(11e)
13C NMR (100 MHz, CDCl3):  = 164.4 (C=N), 150.0 (OC=), 142.0 (4-CH=),
137.6 (5-C), 126.8 (CH2=СН), 116.0 (CH3CH=), 113.2 (CH2=СН), 60.1
(OCH3), 10.9 (CH3CH=).
Following the general procedure (Method A), 1,3-thiazole 11e [Z-iso-
mer (by 1H NMR spectroscopic analysis)] was obtained from 2-aza-
1,3,5-triene 9e (5.83 g, 14.7 mmol) and t-BuOK (1.68 g, 15.0 mmol) in
THF (22.5 mL) and DMSO (4.5 mL) in a yield of 36% (1.95 g) after dou-
ble purification (neutral alumina, hexane, hexane–Et2O, 10:1, 3:1);
yellow-brown crystals, mp 107–108 °C.
15N NMR (40 MHz, CDCl3):  = –72.2.
Anal. Calcd for C9H11NOS (181.3): С, 59.64; Н, 6.12; N, 7.73; S, 17.69.
Found: С, 58.88; Н, 6.05; N, 7.62; S, 17.73.
IR (film from Et2O): 3286 (HC≡), 3090, 2928, 2860, 2103 (C≡C), 1643,
1550, 1494, 1437, 1379, 1302, 1242, 1151, 1108, 1031, 932, 898, 864,
Methyl N-[(1Z)-1-(Allylsulfanyl)-2-ethoxybuta-1,3-dienyl]imino-
formate (10b)
820, 759, 672, 610, 483 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.85 (s, 1 H, 4-CH=), 6.18 (q, 3J = 7.1 Hz,
1 H, CH3CH=), 4.69 (s, 2 H, OCH2Fc), 4.26 (s, 2 H, -H, Fc), 4.17 (br s, 2
H, -H, Fc), 4.12 (s, 5 H, C5H5, Fc), 3.45 (s, 1 H, HC≡), 1.72 (d, 3J = 7.1 Hz,
3 H, CH3CH=).
13C NMR (100 MHz, CDCl3):  = 167.3 (C=N), 148.7 (4-CH=), 147.9
(OC=), 117.0 (5-C), 115.5 (CH3CH=), 84.7 (HC≡), 81.9 (i-C, Fc), 73.8
(C≡), 71.0 (OCH2Fc), 69.6 (-C, Fc), 68.9 (-C, Fc), 68.4 (C5H5, Fc), 11.6
(CH3CH=).
The general experimental procedure was followed using THF (25 mL),
n-BuLi (12 mL, 2.5 M in hexane, 30.0 mmol), ethoxyallene (4.00 g,
47.6 mmol): –55 to –40 °C, 5 min; MeOCH2NCS (2.58 g, 25.0 mmol)/
THF (3 mL): –55 to –43 °C, 15 min; BrCH2CH=CH2 (3.83 g, 31.6 mmol):
–80 → 20 °C, 45 min. The title compound 10b was obtained as a dark-
brown mobile liquid in a yield of 94% (5.36 g).
IR (neat): 1632, 1609 (C=C), 1566, 1554 (C=N) cm–1
.
3
1H NMR (400 MHz, CDCl3):  = 7.99 (s, 1 H, N=CH), 6.85 (dd, Jtrans
17.4 Hz, 3Jcis = 10.8 Hz, 1 H, CH2=СН), 5.80 (ddt, 3Jtrans = 17.0 Hz, 3Jcis
10.0 Hz, 3J = 7.1 Hz, 1 H, SCH2CН=CH2), 5.41 and 5.08 (both dd, 3Jtrans
=
=
=
15N NMR (40 MHz, CDCl3):  = –73.0.
Anal. Calcd for C19H17FeNOS (363.3): C, 62.82; H, 4.72; N, 3.86; S, 8.83.
Found: C, 62.51; H, 4.88; N, 3.71; S, 8.68.
17.4 Hz, 3Jcis = 10.8 Hz, 2 H, CH2=CH), 5.06 (ddt, 3Jtrans = 17.0 Hz, 2J = 1.4
Hz, 4J = 1.2 Hz, 1 H, SCH2CH=CH2), 5.00 (ddt, 3Jcis = 10.0 Hz, 2J = 1.4 Hz,
4J = 0.8 Hz, 1 H, SCH2CH=CH2), 3.87 (q, 3J = 7.1 Hz, 2 H, OCH2CH3), 3.81
(s, 3 H, N=CHOCH3), 3.31 (d, 3J = 7.1 Hz, 2 H, SCH2), 1.35 (t, 3J = 7.1 Hz,
3 H, OCH2CH3).
Methyl N-[(1Z)-1-(Allylsulfanyl)-2-methoxybuta-1,3-dienyl]imi-
noformate (10a)
The general experimental procedure was followed using THF (30 mL),
n-BuLi (14 mL, 2.5 M in hexane, 35.0 mmol), methoxyallene (4.00 g,
57.1 mmol): –53 to –45 °C, 8 min; MeOCH2NCS (3.09 g, 30.0 mmol)
/THF (3 mL): –55 to –45 °C, 13 min; BrCH2CH=CH2 (4.23 g, 34.9
mmol): –75 → 0 to 5 °C, 45 min. The title compound 10a was ob-
tained as a dark-brown liquid in a yield of 76% (4.88 g).
13C NMR (100 MHz, CDCl3):  = 156.5 (N=CH), 150.4 (OC=), 134.2
(SCH2CН=CH2), 129.0 (SC=), 128.1 (CH2=СН), 117.1 (SCH2CН=CH2),
113.0 (CH2=СН), 67.7 (OCH2CH3), 53.8 (N=CHOCH3), 35.1 (SCH2), 15.5
(OCH2CH3).
15N NMR (40 MHz, CDCl3):  = –135.4.
IR (neat): 1631, 1608 (C=C), 1560 (C=N) cm–1
.
2-(1-Ethoxyprop-1-enyl)-5-vinyl-1,3-thiazole (12b)
3
1H NMR (400 MHz, CDCl3):  = 8.01 (s, 1 H, N=CH), 6.82 (dd, Jtrans
17.6 Hz, 3Jcis = 11.0 Hz, 1 H, CH2=СН), 5.80 (ddt, 3Jtrans = 17.0 Hz, 3Jcis
10.0 Hz, 3J = 7.2 Hz, 1 H, SCH2CH=CH2), 5.42 and 5.11 (both dd, 3Jtrans
=
=
=
=
Following the general procedure (Method A), 1,3-thiazole 12b [as a
mixture of Z- and E-isomers in a ratio of ca. 88:12 (estimated by 1H
NMR spectroscopic analysis)] was obtained from 2-aza-1,3,5-triene
10b (5.22 g, 23.0 mmol) and t-BuOK (2.79 g, 24.9 mmol) in THF (31.5
mL) and DMSO (6.5 mL) in a yield of 68% (3.07 g, practically pure by
NMR spectroscopic analysis), after rough purification on neutral alu-
mina. Further separation (neutral alumina, hexane, hexane–Et2O,
10:1) gave compound 12b as a mixture of Z- and E-isomers (1.54 g,
34%); yellow mobile liquid; nD25 1.5711.
3
2
3
17.6 Hz, Jcis = 11.0 Hz, Jgem = 1.8 Hz, 2 H, CH2=СН), 5.06 (ddt, Jtrans
17.0 Hz, 2J = 1.4 Hz, 4J = 1.2 Hz, 1 H, SCH2CH=CH2), 5.02 (ddt, 3Jcis = 10.0
Hz, 2J = 1.4 Hz, 4J = 0.8 Hz, 1 H, SCH2CH=CH2), 3.81 (s, 3 H, N=CHOCH3),
3.68 (s, 3 H, OCH3), 3.30 (d, 3J = 7.2 Hz, 2 H, SCH2).
13C NMR (100 MHz, CDCl3):  = 156.7 (C=N), 151.5 (OC=), 134.2
(SCH2CH=CH2), 128.9 (SC=), 127.6 (CH2=СН), 117.3 (SCH2CH=CH2),
113.5 (CH2=СН), 59.8 (OCH3), 54.0 (N=CHOCH3), 35.2 (SCH2).
Z-Isomer of 1,3-Thiazole 12b
15N NMR (40 MHz, CDCl3):  = –136.2.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

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N. A. Nedolya et al.
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Synthesis
IR (neat): 3089, 3074, 3038, 2979, 2931, 2916, 2884, 2859, 1740,
1714, 1676, 1646, 1621, 1586, 1564, 1507, 1475, 1441, 1389, 1370,
1306, 1264, 1243, 1222, 1149, 1089, 1057, 1007, 977, 932, 901, 858,
mina. Further separation (neutral alumina, hexane–Et2O, 3:1) gave
compound 12c as the Z-isomer [1.06 g (21%), red-orange oily liquid,
22
nD 1.5602] and as a mixture of Z- and E-isomers in a ratio of ca.
826, 762, 711, 666, 597, 510, 481 cm–1
.
66:34 [1.15 g (23%), red-orange oily liquid, nD22 1.5560] in a total yield
of 44% (2.21 g).
3
1H NMR (400 MHz, CDCl3):  = 7.55 (s, 1 H, 4-CH=), 6.75 (dd, Jtrans
=
17.4 Hz, 3Jcis = 10.8 Hz, 1 H, CH2=СН), 6.12 (q, 3J = 7.2 Hz, 1 H, CH3CH=),
5.49 and 5.21 (both d, 3Jtrans = 17.4 Hz, 3Jcis = 10.8 Hz, 2Jgem = 0.4 Hz, 2 H,
CH2=СН), 3.93 (q, J = 7.2 Hz, 2 H, OCH2CH3), 1.82 (d, J = 7.2 Hz, 3 H,
Z-Isomer of 1,3-Thiazole 12c
3
3
IR (neat): 3081, 2957, 2934, 2871, 1709, 1644, 1623, 1568, 1508,
1446, 1396, 1381, 1306, 1243, 1149, 1122, 1068, 1047, 974, 919, 900,
CH3CH=), 1.36 (t, 3J = 7.2 Hz, 3 H, OCH2CH3).
857, 824, 761, 669, 597, 484 cm–1
.
13C NMR (100 MHz, CDCl3):  = 165.0 (C=N), 148.6 (OC=), 141.9 (4-
CH=), 137.4 (5-C), 126.8 (CH2=СН), 115.8 (CH3CH=), 113.4 (CH2=СН),
68.2 (OCH2CH3), 15.4 (OCH2CH3), 11.1 (CH3CH=).
1H NMR (400 MHz, CDCl3):  = 7.55 (s, 1 H, 4-CH=), 6.75 (dd, Jtrans
=
3
17.1 Hz, 3Jcis = 11.0 Hz, 1 H, CH2=СН), 6.11 (q, 3J = 7.3 Hz, 1 H, CH3CH=),
3
3
15N NMR (40 MHz, CDCl3):  = –72.2.
5.50 and 5.22 (both d, Jtrans = 17.1 Hz, Jcis = 11.0 Hz, 2 H, CH2=СН),
3.85 (t, 3J = 6.6 Hz, 2 H, OCH2C3H7), 1.82 (d, 3J = 7.3 Hz, 3 H, CH3CH=),
1.75–1.72 (m, 2 H, OCH2CH2C2H5), 1.52–1.46 [m, 2 H, O(CH2)2CH2CH3],
0.96 [t, 3J = 7.3 Hz, 3 H, O(CH2)3CH3].
Anal. Calcd for C10H13NOS (195.3): С, 61.50; Н, 6.71; N, 7.17; S, 16.42.
Found: С, 61.38; Н, 6.69; N, 7.17; S, 16.38.
13C NMR (100 MHz, CDCl3):  = 165.0 (C=N), 148.9 (OC=), 142.0 (4-
CH=), 137.5 (5-C), 126.9 (CH2=СН), 115.9 (CH3CH=), 113.2 (CH2=СН),
72.5 (OCH2C3H7), 32.2 (OCH2CH2C2H5), 19.1 [O(CH2)2CH2CH3], 13.8
[O(CH2)3CH3], 11.2 (CH3CH=).
E-Isomer of 1,3-Thiazole 12b (Tentative Assignment)
1H NMR (400 MHz, CDCl3):  = 7.64 (s, 1 H, 4-CH=), 6.78 (dd, Jtrans
=
=
3
3
3
17.4 Hz, Jcis = 11.0 Hz, 1 H, CH2=СН), 5.71 and 5.40 (both d, Jtrans
17.4 Hz, 3Jcis = 11.0 Hz, 2 H, CH2=СН), 5.13 (q, 3J = 7.4 Hz, 1 H, CH3CH=),
15N NMR (40 MHz, CDCl3):  = –73.8.
3
3
3.85 (q, J = 7.1 Hz, 2 H, OCH2CH3), 2.13 (d, J = 7.4 Hz, 3 H, CH3CH=),
1.41 (t, 3J = 7.1 Hz, 3 H, OCH2CH3).
Anal. Calcd for C12H17NOS (223.3): С, 64.53; Н, 7.67; N, 6.27; S, 14.36.
Found: С, 64.38; Н, 7.59; N, 6.17; S, 14.28.
13C NMR (100 MHz, CDCl3):  = 164.0 (C=N), 147.1 (OC=), 141.5 (4-
CH=), 137.1 (5-C), 125.9 (CH2=СН), 119.3 (CH2=СН), 102.1 (CH3CH=),
64.0 (OCH2CH3), 14.5 (OCH2CH3), 12.2 (CH3CH=).
E-Isomer of 1,3-Thiazole 12c (Tentative Assignment)
The 1H–13C HSQC 2D experiment provided additional support for the
proposed structure.
IR (film) (Z- and E-isomers in a ratio of ca. 65:35): 3082, 2957, 2931,
2871, 1713, 1637, 1626, 1584, 1511, 1452, 1382, 1333, 1306, 1233,
1154, 1112, 1070, 976, 918, 903, 857, 825, 794, 760, 697, 669, 596,
567, 483 cm–1
.
Methyl N-[(1Z)-1-(Allylsulfanyl)-2-butoxybuta-1,3-dienyl]imino-
formate (10c)
3
1H NMR (400 MHz, CDCl3):  = 7.64 (s, 1 H, 4-CH=), 6.76 (dd, Jtrans
=
=
3
3
17.1 Hz, Jcis = 11.0 Hz, 1 H, CH2=СН), 5.54 and 5.23 (both d, Jtrans
The general experimental procedure was followed using THF (25 mL),
n-BuLi (12 mL, 2.5 M in hexane, 30.0 mmol), n-butoxyallene (3.37 g,
30.0 mmol): –55 to –38 °C, 7 min; MeOCH2NCS (2.58 g, 25.0 mmol)
/THF (3 mL): –40 to –35 °C, 12 min; BrCH2CH=CH2 (3.87 g, 32.0 mmol):
–80 → 20 °C, 1 h. The title compound 10c was obtained as a dark-
brown mobile liquid in a yield of 91% (5.82 g).
17.1 Hz, 3Jcis = 11.0 Hz, 2 H, CH2=СН), 5.13 (q, 3J = 7.5 Hz, 1 H, CH3CH=),
3.79 (t, 3J = 6.6 Hz, 2 H, OCH2C3H7), 2.13 (d, 3J = 7.5 Hz, 3 H, CH3CH=),
1.75–1.72 (m, 2 H, OCH2CH2C2H5), 1.52–1.46 [m, 2 H, O(CH2)2CH2CH3],
0.96 [t, 3J = 7.3 Hz, 3 H, O(CH2)3CH3].
13C NMR (100 MHz, CDCl3):  = 164.2 (C=N), 147.2 (OC=), 141.6 (4-
CH=), 137.1 (5-C), 126.8 (CH2=СН), 116.2 (CH3CH=), 101.7 (CH2=СН),
68.2 (OCH2C3H7), 31.2 (OCH2CH2C2H5), 19.3 [O(CH2)2CH2CH3], 13.8
[O(CH2)3CH3], 12.3 (CH3CH=).
IR (neat): 1633 (C=C), 1554, 1518 (C=N) cm–1
.
3
1H NMR (400 MHz, CDCl3):  = 7.99 (s, 1 H, N=CH), 6.84 (dd, Jtrans
17.4 Hz, 3Jcis = 10.8 Hz, 1 H, CH2=СН), 5.80 (ddt, 3Jtrans = 17.0 Hz, 3Jcis
9.8 Hz, 3J = 6.9 Hz, 1 H, SCH2CН=CH2), 5.41 and 5.07 (both dd, 3Jtrans
=
=
=
15N NMR (40 MHz, CDCl3):  = –63.3.
17.4 Hz, 3Jcis = 10.8 Hz, 2Jgem = 1.7 Hz, 2 H, CH2=СН), 5.06 and 5.01 (both
3
3
Methyl N-[(1Z)-1-(Allylsulfanyl)-2-(1-ethoxyethoxy)buta-1,3-die-
nyl]iminoformate (10d)
br d, Jtrans = 17.0 Hz, Jcis = 9.8 Hz, 2 H, SCH2CН=CH2), 3.81 (s, 3 H,
N=CHOCH3), 3.80 (t, 3J = 6.6 Hz, 2 H, OCH2C3H7), 3.31 (d, 3J = 6.9 Hz, 2
H, SCH2), 1.76–1.69 (m, 2 H, OCH2CH2C2H5), 1.54–1.44 [m, 2 H, O(CH2)
2CH2CH3], 0.96 [t, 3J = 7.3 Hz, 3 H, O(CH2)3CH3].
The general experimental procedure was followed using THF (25 mL),
n-BuLi (12 mL, 2.5 M in hexane, 30.0 mmol), 1-(1-ethoxyethoxy)al-
lene (3.72 g, 29.0 mmol): –55 to –35 °C, 5 min; MeOCH2NCS (2.58 g,
25.0 mmol)/THF (3 mL): –60 to –45 °C, 15 min; BrCH2CH=CH2 (3.83 g,
31.6 mmol): –80 → 18 °C, 1 h. The title compound 10d was obtained
as a brown viscous liquid in a yield of 93% (6.30 g).
13C NMR (100 MHz, CDCl3):  = 156.5 (N=CH), 150.5 (OC=), 134.2
(SCH2CН=CH2), 129.0 (SC=), 128.1 (CH2=СН), 117.1 (SCH2CН=CH2),
113.0 (CH2=СН), 71.9 (OCH2C3H7), 53.8 (N=CHOCH3), 35.2 (SCH2), 32.3
(OCH2CH2C2H5), 19.2 [O(CH2)2CH2CH3], 13.9 [O(CH2)3CH3].
The 1H–13C HMBC and 1H–13C HSQC 2D experiments provided addi-
tional support for the proposed structure.
IR (neat): 1632 (C=C), 1567 (C=N) cm–1
.
3
1H NMR (400 MHz, CDCl3):  = 8.00 (s, 1 H, N=CH), 6.95 (dd, Jtrans
17.4 Hz, 3Jcis = 10.0 Hz, 1 H, CH2=СН), 5.80 (ddt, 3Jtrans = 17.0 Hz, 3Jcis
10.0 Hz, 3J = 7.1 Hz, 1 H, SCH2CН=CH2), 5.56 and 5.10 (both dd, 3Jtrans
=
=
=
2-(1-Butoxyprop-1-enyl)-5-vinyl-1,3-thiazole (12c)
17.4 Hz, 3Jcis = 10.0 Hz, 2Jgem = 1.8 Hz, 2 H, CH2=СН), 5.26 (q, 3J = 5.1 Hz,
1 H, OCHO), 5.06 and 5.00 (both ddt, 3Jtrans = 17.0 Hz, 3Jcis = 10.0 Hz, 2J =
1.5 Hz, 4J = 0.8 Hz, 2 H, SCH2CН=CH2), 3.84 and 3.61 (both dq, 2J = 9.3
Hz, 3J = 7.2 Hz, 2 H, OCH2CH3), 3.81 (s, 3 H, N=CHOCH3), 3.30 and 3.27
(both dd, 2J = 13.3 Hz, 3J = 7.1 Hz, 2 H, SCH2), 1.46 [d, 3J = 5.1 Hz, 3 H,
OCH(CH3)O], 1.16 (t, 3J = 7.2 Hz, 3 H, OCH2CH3).
Following the general procedure (Method A), 1,3-thiazole 12c [as a
mixture of Z- and E-isomers in a ratio of ca. 83:17 (estimated by 1H
NMR spectroscopic analysis)] was obtained from 2-aza-1,3,5-triene
10c (5.69 g, 22.3 mmol) and t-BuOK (2.80 g, 25.0 mmol) in THF (31.5
mL) and DMSO (6.5 mL) in a yield of 58% (2.86 g, practically pure by
NMR spectroscopic analysis), after rough purification on neutral alu-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

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N. A. Nedolya et al.
Paper
Synthesis
13C NMR (100 MHz, CDCl3):  = 156.4 (N=CH), 149.0 (OC=), 134.0
(SCH2CН=CH2), 129.6 (CH2=СН), 128.5 (SC=), 117.2 (SCH2CН=CH2),
114.0 (CH2=СН), 103.0 (OCHO), 64.2 (OCH2CH3), 53.8 (N=CHOCH3),
35.2 (SCH2), 21.1 [OCH(CH3)O], 15.3 (OCH2CH3).
IR (neat): 1631 (C=C), 1561 (C=N) cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.01 (s, 1 H, N=CH), 6.86 (dd, Jtrans
17.0 Hz, 3Jcis = 10.8 Hz, 1 H, CH2=СН), 5.80 (ddt, 3Jtrans = 17.0 Hz, 3Jcis
10.0 Hz, 3J = 7.0 Hz, 1 H, SCH2CН=CH2), 5.45 and 5.10 (both br d, 3Jtrans
=
=
=
3
17.4 Hz, 3Jcis = 10.8 Hz, 2Jgem = 1.2 Hz, 2 H, CH2=СН), 5.06 and 5.02 (both
3
3
2-[1-(1-Ethoxyethoxy)prop-1-enyl]-5-vinyl-1,3-thiazole (12d)
br d, Jtrans = 17.0 Hz, Jcis = 10.0 Hz, 2 H, SCH2CН=CH2), 4.62 (s, 2 H,
OCH2Fc), 4.32 and 4.16 (both s, 4 H, C5H4, Fc), 4.14 (s, 5 H, C5H5, Fc),
3.81 (s, 3 H, N=CHOCH3), 3.31 (d, 3J = 7.0 Hz, 2 H, SCH2).
Following the general procedure (Method A), 1,3-thiazole 12d [as a
mixture of Z- and E-isomers in a ratio of ca. 90:10 (estimated by 1H
NMR spectroscopic analysis)] was obtained from 2-aza-1,3,5-triene
10d (5.84 g, 21.5 mmol) and t-BuOK (2.80 g, 25.0 mmol) in THF (31.5
mL) and DMSO (6.5 mL) in a yield of 73% (3.73 g, practically pure by
NMR spectroscopic analysis), after rough purification on neutral alu-
mina. Further separation (neutral alumina, hexane, hexane–Et2O,
13C NMR (100 MHz, CDCl3):  = 156.5 (N=CH), 150.3 (OC=), 134.2
(SCH2CН=CH2), 129.3 (SC=), 128.1 (CH2=СН), 117.2 (SCH2CН=CH2),
113.5 (CH2=СН), 82.9 (i-C, Fc), 70.3 (OCH2Fc), 69.5 (-C, Fc), 68.5 (-C,
Fc), 68.4 (C5H5, Fc), 53.8 (N=CHOCH3), 35.3 (SCH2).
22
10:1) gave compound 12d (0.83 g, 16%); light-yellow oily liquid; nD
2-[1-(Ferrocenylmethoxy)prop-1-enyl]-5-vinyl-1,3-thiazole (12e)
1.5535.
Following the general procedure (Method A), 1,3-thiazole 12e [as a
mixture of Z- and E-isomers in a ratio of ca. 90:10 (estimated by 1H
NMR spectroscopic analysis)] was obtained from 2-aza-1,3,5-triene
10e (5.86 g, 14.7 mmol) and t-BuOK (1.68 g, 15.0 mmol) in THF (29.5
mL) and DMSO (4.5 mL) in a yield of 64% (3.42 g, practically pure by
NMR spectroscopic analysis), after rough purification on neutral alu-
mina. Further separation (neutral alumina, hexane–Et2O, 3:1, 1:1)
gave compound 12e (2.32 g, 43%) as a dark-brown viscous liquid.
Z-Isomer of 1,3-Thiazole 12d
IR (neat): 3081, 2957, 2934, 2871, 1709, 1644, 1623, 1568, 1508,
1446, 1396, 1381, 1306, 1243, 1149, 1122, 1068, 1047, 974, 919, 900,
857, 824, 761, 669, 597, 484 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.55 (s, 1 H, 4-CH=), 6.75 (dd, Jtrans
=
3
17.1 Hz, 3Jcis = 10.8 Hz, 1 H, CH2=СН), 6.11 (q, 3J = 7.3 Hz, 1 H, CH3CH=),
3
3
5.51 and 5.23 (both d, Jtrans = 17.1 Hz, Jcis = 10.8 Hz, 2 H, CH2=СН),
5.20 (q, 3J = 5.4 Hz, 1 H, OCHO), 3.82 and 3.58 (both dq, 2J = 9.5 Hz, 3J =
Z-Isomer of 1,3-Thiazole 12e
3
3
7.2 Hz, 2 H, OCH2CH3), 1.87 (d, J = 7.3 Hz, 3 H, CH3CH=), 1.47 [d, J =
IR (neat): 3089, 2925, 2861, 1678, 1638, 1506, 1441, 1405, 1382,
1301, 1241, 1179, 1147, 1111, 1034, 1001, 976, 920, 903, 854, 820,
5.4 Hz, 3 H, OCH(CH3)O], 1.15 (t, 3J = 7.2 Hz, 3 H, OCH2CH3).
The 1H–1H NOESY 2D experiment provided additional support for the
proposed structure.
13C NMR (100 MHz, CDCl3):  = 165.0 (C=N), 146.5 (OC=), 141.7 (4-
CH=), 137.6 (5-C), 126.7 (CH2=СН), 116.2 (CH3CH=), 115.0 (CH2=СН),
102.1 (OCHO), 64.4 (OCH2CH3), 21.0 [OCH(CH3)O], 15.3 (OCH2CH3),
11.7 (CH3CH=).
761, 696, 674, 594, 488 cm–1
.
3
1H NMR (400 MHz, CDCl3):  = 7.57 (s, 1 H, 4-CH=), 6.76 (dd, Jtrans
=
17.4 Hz, 3Jcis = 11.0 Hz, 1 H, CH2=СН), 6.10 (q, 3J = 7.3 Hz, 1 H, CH3CH=),
5.51 and 5.22 (both d, Jtrans = 17.4 Hz, Jcis = 11.0 Hz, 2 H, CH2=СН),
4.69 (s, 2 H, OCH2Fc), 4.26 (br s, 2 H, -H, Fc), 4.16 (br s, 2 H, -H, Fc),
4.11 (s, 5 H, C5H5, Fc), 1.68 (d, 3J = 7.3 Hz, 3 H, CH3CH=).
3
3
15N NMR (40 MHz, CDCl3):  = –70.3.
13C NMR (100 MHz, CDCl3):  = 164.8 (C=N), 148.0 (OC=), 141.9 (4-
CH=), 137.5 (5-C), 126.8 (CH2=СН), 116.0 (CH2=СН), 114.6 (CH3CH=),
82.0 (i-C, Fc), 70.7 (OCH2Fc), 69.5 (-C, Fc), 68.7 (-C, Fc), 68.3 (C5H5,
Fc), 11.4 (CH3CH=).
Anal. Calcd for С12Н17NO2S (239.3): С, 60.22; Н, 7.16; N, 5.85; S, 13.40.
Found: С, 60.17; H, 7.09; N, 5.83; S, 13.38.
The 1H–13C HMBC and 1H–13C HSQC 2D experiments provided addi-
tional support for the proposed structure.
15N NMR (40 MHz, CDCl3):  = –72.9.
E-Isomer of 1,3-Thiazole 12d (Tentative Assignment)
1H NMR (400 MHz, CDCl3):  = 7.65 (s, 1 H, 4-CH=), 6.77 (dd, Jtrans
=
3
17.1 Hz, 3Jcis = 10.8 Hz, 1 H, CH2=СН), 6.11 (q, 3J = 7.3 Hz, 1 H, CH3CH=),
3
3
5.55 and 5.24 (both d, Jtrans = 17.1 Hz, Jcis = 10.8 Hz, 2 H, CH2=СН),
Anal. Calcd for С19Н19FeNOS (365.3): С, 62.48; Н, 5.24; N, 3.83; S, 8.78.
Found: С, 62.27; H, 5.12; N, 3.91; S, 8.61.
5.20 (q, 3J = 5.4 Hz, 1 H, OCHO), 3.79 and 3.55 (both dq, 2J = 9.5 Hz, 3J =
7.1 Hz, 2 H, OCH2CH3), 2.14 (d, J = 7.3 Hz, 3 H, CH3CH=), 1.47 [d, J =
5.4 Hz, 3 H, OCH(CH3)O], 1.20 (t, 3J = 7.1 Hz, 3 H, OCH2CH3).
3
3
E-Isomer of 1,3-Thiazole 12e (Tentative Assignment)
13C NMR (100 MHz, CDCl3):  = 164.3 (C=N), 145.3 (OC=), 141.8 (4-
CH=), 137.2 (5-C), 126.8 (CH2=СН), 116.2 (CH3CH=), 109.4 (CH2=СН),
100.7 (OCHO), 61.8 (OCH2CH3), 20.2 [OCH(CH3)O], 15.0 (OCH2CH3),
12.6 (CH3CH=).
3
1H NMR (400 MHz, CDCl3):  = 7.66 (s, 1 H, 4-CH=), 6.78 (dd, Jtrans
=
17.2 Hz, 3Jcis = 10.7 Hz, 1 H, CH2=СН), 6.11 (q, 3J = 7.4 Hz, 1 H, CH3CH=),
3
3
5.55 and 5.48 (both d, Jtrans = 17.2 Hz, Jcis = 10.7 Hz, 2 H, CH2=СН),
4.62 (s, 2 H, OCH2Fc), 4.30 (t, 3J = 1.9 Hz, 2 H, -H, Fc), 4.21 (t, 3J = 1.9
Hz, 2 H, -H, Fc), 4.15 (s, 5 H, C5H5, Fc), 2.17 (d, 3J = 7.4 Hz, 3 H,
CH3CH=).
Methyl N-[(1Z)-1-(Allylsulfanyl)-2-(ferrocenylmethoxy)buta-1,3-
dienyl]iminoformate (10e)
13C NMR (100 MHz, CDCl3):  = 164.9 (C=N), 147.2 (OC=), 141.7 (4-
CH=), 137.4 (5-C), 126.9 (CH2=СН), 116.1 (CH2=СН), 114.8 (CH3CH=),
90.8 (i-C, Fc), 68.6 (-C, Fc), 68.2 (C5H5, Fc), 67.8 (-C, Fc), 67.3
(OCH2Fc), 12.4 (CH3CH=).
The 1H–13C HMBC and 1H–13C HSQC 2D experiments provided addi-
tional support for the proposed structure.
The general experimental procedure was followed using THF (25 mL),
n-BuLi (6.5 mL, 2.37 M in hexane, 15.4 mmol), 1-(ferrocenylmethoxy)
allene (3.81 g, 15.0 mmol): –45 to –43 °C, 7 min; MeOCH2NCS (1.55 g,
15.0 mmol)/THF (5 mL): –45 to –40 °C, 12 min; BrCH2CH=CH2 (3.10 g,
25.6 mmol): 0–5 °C, 1 h. The title compound 10e was obtained as a
dark-brown liquid in a yield of ca. 100% (6.00 g).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

L
N. A. Nedolya et al.
Paper
Synthesis
Acknowledgment
Trofimov, B. A. Russ. Chem. Bull. 2011, 60, 2617. (d) Tarasova, О.
А.; Nedolya, N. А.; Аlbanov, А. I.; Trofimov, B. А. Russ. J. Gen.
Chem. 2016, 86, 2551. (e) Tarasova, O. A.; Nedolya, N. A.;
Аlbanov, А. I.; Trofimov, B. А. Russ. J. Org. Chem. 2017, 53, 305.
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lands, 1999; (b) Brandsma, L.; Nedolya, N. A.; Tarasova, O. A.;
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1241. (c) Brandsma, L. Eur. J. Org. Chem. 2001, 4569. (d)
Brandsma, L.; Nedolya, N. A. Synthesis 2004, 735. (e) Nedolya, N.
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(6) (a) Nedolya, N. A.; de Lang, R.-J.; Brandsma, L.; Trofimov, B. A.
Abstracts of the 11th International Conference on Organic Synthe-
sis, Amsterdam, The Netherlands, June 30–July 4, 1996, 251. (b)
Brandsma, L.; Trofimov, B.; Nedolya, N.; Mal’kina, A. Abstracts
of the 17th International Symposium on the Organic Chemistry of
Sulfur, Tsukuba, Japan, July 7–12, 1996, 234. (c) Nedolya, N. A.;
Brandsma, L.; Tarasova, O. A.; Albanov, A. I.; Trofimov, B. A. Russ.
J. Org. Chem. 2011, 47, 659. (d) Nedolya, N. A.; Tarasova, O. A.;
Аlbanov, А. I.; Trofimov, B. А. Russ. J. Org. Chem. 2017, 53, 134.
(7) (a) Nedolya, N. A.; Dmitrieva, L. L.; Albanov, A. I.; Klyba, L. V.;
Tarasova, O. A.; Ushakov, I. A. Russ. J. Org. Chem. 2006, 42, 465.
(b) Nedolya, N. A.; Tarasova, O. A.; Albanov, A. I.; Volostnykh, O.
G.; Brandsma, L.; Trofimov, B. A. Mendeleev Commun. 2008, 18,
164. (c) Nedolya, N. A.; Tarasova, O. A.; Volostnykh, O. G.;
Albanov, A. I.; Trofimov, B. A. J. Organomet. Chem. 2011, 696,
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(8) (a) Nedolya, N. A.; Tarasova, O. A.; Volostnykh, O. G.; Albanov, A.
I.; Trofimov, B. A. Chem. Heterocycl. Compd. (Engl. Transl.) 2012,
47, 1430. (b) Nedolya, N. A.; Tarasova, O. A.; Albanov, A. I.;
Trofimov, B. A. Tetrahedron Lett. 2014, 55, 2495. (c) Nedolya, N.
A.; Tarasova, O. A.; Albanov, A. I.; Klyba, L. V.; Trofimov, B. A. Tet-
rahedron 2017, 73, 1085.
(9) (a) Sakamoto, T.; Nagata, H.; Kondo, Y.; Shiraiwa, M.; Yamanaka,
H. Chem. Pharm. Bull. 1987, 35, 823. (b) Hodgetts, K. J.; Kershaw,
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(10) Kazmaier, U.; Persch, A. Org. Biomol. Chem. 2010, 8, 5442.
(11) (a) Nedolya, N. A.; Schlyakhtina, N. I.; Klyba, L. V.; Ushakov, I. A.;
Fedorov, S. V.; Brandsma, L. Tetrahedron Lett. 2002, 43, 9679. (b)
Nedolya, N. A.; Brandsma, L.; Schlyakhtina, N. I.; Fedorov, S. V.
Chem. Heterocycl. Compd. (Engl. Transl.) 2002, 38, 622. (c)
Nedolya, N. A.; Tarasova, O. A.; Albanov, A. I.; Trofimov, B. A.
Chem. Heterocycl. Compd. (Engl. Transl.) 2011, 46, 1536. (d)
Nedolya, N. A.; Tarasova, O. A.; Albanov, A. I.; Trofimov, B. A.
Russ. J. Org. Chem. 2015, 51, 281.
(12) (a) Siddiqui, N.; Arshad, M. F.; Ahsan, W.; Alam, M. S. Int. J.
Pharm. Sci. Drug Res. 2009, 1, 136. (b) Davyt, D.; Serra, G. Mar.
Drugs 2010, 8, 2755. (c) Siddiqui, N.; Arya, S. K.; Ahsan, W.;
Azad, B. Int. J. Drug Dev. Res. 2011, 3, 55. (d) Zagade, A. A.;
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Med. Chem. Res. 2012, 21, 2123. (f) Morigia, R.; Locatellia, A.;
Leonia, A.; Rambaldi, M. Recent Pat. Anti-Cancer Drug Discovery
2015, 10, 280.
This work was carried out using the equipment of the Baikal Analytical
Centre for Collective Use, SB RAS (Siberian Branch of the Russian
Academy of Sciences).
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1609561.
S
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ortioInfgrmoaitn
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L