Synthesis of functionalized thiazoles via attack of heterocyclic nucleophiles on allenyl isothiocyanates

Article abstract of DOI:10.1016/j.tet.2008.03.074

New examples of substituted thiazole derivatives carrying different heterocyclic ring systems at C-2 position were prepared via the reaction of several allenyl isothiocyanates with nucleophiles such as imidazoles, pyrazoles, benzimidazoles, indazole, 1,2,

Full text of DOI:10.1016/j.tet.2008.03.074

Tetrahedron 64 (2008) 5590–5597
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of functionalized thiazoles via attack of heterocyclic
nucleophiles on allenyl isothiocyanatesq
*
Baker Jawabrah Al-Hourani, Klaus Banert , Nermeen Gomaa, Kai Vrobel
Institute of Chemistry, Chemnitz University of Technology, Strasse der Nationen 62, 09111 Chemnitz, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
New examples of substituted thiazole derivatives carrying different heterocyclic ring systems at C-2
position were prepared via the reaction of several allenyl isothiocyanates with nucleophiles such as
imidazoles, pyrazoles, benzimidazoles, indazole, 1,2,3-triazole, 1,2,4-triazole, and 1H-benzotriazole.
Although these allenyl isothiocyanates are very reactive electrophiles and tend to polymerize, the yield of
the thiazole products ranked between modest and very good. The regiochemistry of the reactions was
proved by NMR and X-ray studies indicating that the attack of ambident nucleophiles proceeded very
selectively. In some cases, however, the products were formed as mixtures of aromatic heterocycles and
non-aromatic isomers. The latter could be rearranged to yield the uniform aromatic thiazoles.
Ó 2008 Published by Elsevier Ltd.
Received 30 January 2008
Accepted 19 March 2008
Available online 26 March 2008
Keywords:
Allenes
Isothiocyanates
Addition reactions
Ring closure
Thiazoles
Heterocycles
R2
R2
1. Introduction
[3,3]
R1
C
SCN
Isothiocyanates are extremely useful in organic synthesis.2,3
Thus, several methods to prepare such compounds were de-
veloped.3,4 The only access to allenyl isothiocyanates of type 2 is
based on the [3,3]-sigmatropic rearrangement of propargyl thio-
cyanates 1 (Scheme 1).5 This rearrangement is derived from the
well known isomerization of allyl thiocyanate to allyl iso-
thiocyanate.6 However, the process 1/2 can be successfully per-
formed only by the technique of flash vacuum pyrolysis (FVP)
because neat (undiluted) cumulenes 2 tend to exothermic sponta-
neous polymerization even at rt.5 Whereas allenyl isothiocyanates
like 2a and 2b can be obtained nearly quantitatively in 100 g
batches per day, there are some limitations in other cases such as 2c
and 2e–2g. The yields of 2e and 2f are diminished to 73% and 60%,
respectively, since the precursors 1e and 1f cannot be vaporized
without decomposition. Flash vacuum pyrolyses of 1c or 1g lead to
equilibria with 2c or 2g, respectively (ratios 1c/2c¼17:83 and 1g/
2g¼89:11). In the case of 1d,7 the analogous process gives rise to
a mixture with 1d/2d¼4:96 in 95% yield.8 This equilibrium ratio can
be verified by renewed flash vacuum pyrolysis of 2d, which was
separated by liquid chromatography.
R1
NCS
2
1
R1
a R1 = R2 = H
b R1 = H, R2 = Me
c R1 = Me, R2 = H
N
d R1 = CH2OMe, R2 = H
e R1 = CH2OAc, R2 = H
S
3
R2
f
R
1 = CH2Cl, R2 = H
g R1 = SiMe3, R2 = H
Scheme 1.
Recently, treatment of allenyl isothiocyanates 2 with simple
nucleophiles was utilized to prepare substituted thiazoles9 bearing
a functional group at the C-2 position.5 We present now the
reactions of the highly reactive cumulenes 2 with the weak nu-
cleophile water and with five-membered heterocycles to reveal
regioselectively thiazole derivatives. Thus, the chemistry of 2
illustrates that allenyl isothiocyanates act predominantly as mani-
fold synthetic equivalents of synthons 3.
2. Results and discussion
2.1. Subsequent reactions of allenyl isothiocyanate (2a) with
water
q
See Ref. 1.
The allenyl isothiocyanate (2a) is extremely reactive, as is ex-
emplified by its conversion into 2-diphenylamino-5-methylthiazole
* Corresponding author. Tel.: þ49 371 531 31463; fax: þ49 371 531 21229.
E-mail address: klaus.banert@chemie.tu-chemnitz.de (K. Banert).
0040-4020/$ – see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tet.2008.03.074

B. Jawabrah Al-Hourani et al. / Tetrahedron 64 (2008) 5590–5597
5591
H
C
H2O
THF
2 H2O
H
C
+
+
+
CO2
H2S
NH3
3 x 2a
Me
HN
S
O
N
NCS
OH
4
2 x 2a
2a
Me
N
S
Me
S
S
S
N
HN
6
2
1
N
43%
Me
O
3
S
N
Me
S
5
S
4
N
4%
7
Me
23%
Me
S
N
N
N
HN
HN
10
Me
Me
H2N
Me
S
S
9
S
S
8
Scheme 2.
with diphenylamine at rt.5d Phenyl isothiocyanate is only attacked
by this weak nitrogen nucleophile at 280 ꢀC.10 Thus, it was not
surprising that 2a readily formed heterocyclic products on treat-
ment with water/THF (1:2) already at rt although normal
isothiocyanates are known to react so slowly that they can be
purified by steam distillation. However, the expected thiazole 5,11
which is available from 2a and diluted aqueous NaOH in 86% yield,5d
was generated only as a side product with 4% yield (Scheme 2).
Instead, the main reactions led to the unexpected compounds 6 and
7. These products are possibly derived from the intermediate 4,
which is not only able to cyclize to afford 5 but, as a labile thio-
carbamic acid, can also decompose to acrolein, carbon dioxide, hy-
drogen sulfide, and ammonia. The latter two compounds are more
nucleophilic thanwater and subsequently react with 2a to afford the
major products 6 and 7 via the intermediates 8 as well as 9 and 10,
respectively. In accordance with this reaction pathway, 6 can be
prepared in higher yield (77%) from 2a and H2S/H2O or in 99.6%
yield from 2a and thiazole 8.12 Similarly, the synthesis of 7 was
performed with 2a and less than stoichiometric quantities of
aqueous ammonia (88% yield) or with 2a and 913 (90%). The
intermediate for these reactions, namely compound 10, can be
isolated and treated with 2a to give 7. The formation of 10 from 9
shows that thiazole derivatives can be produced selectively and
effectively by the attack of heterocyclic nitrogen atoms on allenyl
isothiocyanates. Thus, we were encouraged to investigate the
reaction of these cumulenes with further nitrogen heterocycles.
selectively the products 12ak and 12am, respectively, bearing the
thiazole ring at N-1 instead of N-2. Although 11l is known16 to
furnish mixtures of 1H-1,2,3-triazoles and 2H-1,2,3-triazoles by
treatment with common electrophiles like alkyl halides or
Table 1
Reactions of allenyl isothiocyanates 2a–d with nucleophiles 11a–m
R2
R1
H
R1
N
N
R1
R2
C
+
NuH
+
Nu
Nu
S
S
NCS
R2
13
12
2
11a-m
a R1 = R2 = H
b R1 = H; R2 = Me
c R1 = Me; R2 = H
d R1 = CH2OMe; R2 = H
CDCl3 (100%)
Allene 2 Nucleophile 11a Solvent Reaction time 12 Yield (%) 13 Yield (%)
a
b
c
d
a
d
a
a
b
c
d
a
d
a
d
a
d
a
a
a
d
a
a
a
a
a
a
a
b
b
c
d
d
d
d
e
e
f
THF
THF
THF
THF
THF
THF
DMF
THF
THF
THF
THF
CH2Cl2 2 h
CH2Cl2 5 h
CHCl3
CHCl3
CH2Cl2 3 h
CH2Cl2 6 h
THF
THF
THF
THF
THF
THF
THF
1 h
aa 80
ba 56
ca 80
da 74
ab 80
db 79
ac 68
ad 90
bd 19
cd 77
dd 91
ae 49
de 50
d
d
5 days
1 day
2 h
1 h
1 h
5 days
5 h
6 days
3 days
2 days
ba 25
d
d
da 13
ab 10
db
d
d
3
d
d
bd 27
d
d
d
d
2.2. Reactions of allenyl isothiocyanates with azole
nucleophiles
ae 33
de 30
af 22
df 46
d
d
d
d
d
24 h
24 h
af
66
A new family of substituted thiazole derivatives carrying dif-
ferent heterocyclic ring systems at C-2 position was prepared via
the reaction of the allenyl isothiocyanates 2a–c and 2d8 with the
imidazoles 11a–c, pyrazoles 11d–g,14,15 benzimidazoles 11h–j,
indazole (11k), 1,2,3-triazole (11l), benzotriazole (11m), and 1,2,4-
triazole (11n) (Table 1 and Scheme 3). Due to the symmetrical
structure of the corresponding azole reagents, several trans-
formations afforded a single aromatic thiazole product exclusively
in good to excellent yields, such as 12aa, 12ca, 12ad, 12cd, 12dd,
12ah, and 12aj. In the case of 11i, only the ring nitrogen, but not the
primary amine, attacked the allenyl isothiocyanate (2a) to induce
formation of thiazole 12ai. In order to maintain the favorable aro-
matic benzo unit, indazole (11k) and benzotriazole (11m) yielded
f
df 39
ag 91
dg 88
ah 85
g
g
h
i
j
j
k
l
m
d
d
d
d
d
3 h
30 min
1 day
40 h
24 h
7 days
7 days
ai
aj
dj
83
82
76
dj 17
ak 95
al 69
am 86
d
d
d
d
d
d
a
Nucleophiles 11: 1H-imidazole (11a); 2-ethyl-4-methyl-1H-imidazole (11b); 4-
nitro-1H-imidazole (11c); 1H-pyrazole (11d); 3,5-dimethyl-1H-pyrazole (11e);
3,4,5-trimethyl-1H-pyrazole (11f);14 2-(1H-pyrazol-3-yl)-pyridine (11g);15 1H-
benzimidazole (11h); 1H-benzimidazol-2-ylamine (11i); 2-ethyl-1H-benzimidazole
(11j); 1H-indazole (11k); 1H-1,2,3-triazole (11l), and 1H-benzotriazole (11m).

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B. Jawabrah Al-Hourani et al. / Tetrahedron 64 (2008) 5590–5597
R4
acylating compounds, the reaction with 2a led to the sole product
1-(5-methylthiazol-2-yl)-1H-1,2,3-triazole (12al). In contrast to
that the analogous transformation of 11n gave a mixture of 12an
and 12an0 as shown in Scheme 3. The assignment of the hetero-
cycles 12an and 12an0 was easily performed by NMR spectroscopy.
R1
C
N3
+
1
R3
NCS
N
H
11b R3 = Et; R4 = Me
2a,d
11c R3 = H; R4 = NO2
2
N
1
C
NCS
2a
+
N
H
N
attack
of N-3
attack
of N-1
11n
7 days THF
R1
R1
R4
N
R3
N
N
N
N
Me
S
Me
S
N
attack
of N-4
f
ck o
atta
R3
R4
N-1 or N-2
12ab R1 = H; R3 = Et; R4 = Me
12ac R1 = H; R3 = H; R4 = NO2
15
N
N
12db R1 = CH2OMe; R3 = Et; R4 = Me
N
N
Me
S
N
N
N
Me
S
H
N
R1
N
12an' (26%)
12an (64%)
Me
CH2
N
S
Scheme 3.
N
Me
In the case of less symmetrical azole nucleophiles such as 11b,
11c, and 11g, two non-equivalent nitrogen atoms could attack the
allenyl isothiocyanate 2 resulting in two different aromatic thiazole
derivatives as depicted in Schemes 4 and 5. Since we always
obtained only one aromatic product in each transformation, we
assumed that the sterically less hindered nitrogen atom, namely
N-1 of 11b,c and N-10 of 11g, should bind to the electrophilic carbon
of the isothiocyanate 2. However, we were not able to exclude the
alternative structures 14 and 15 by NMR methods. Fortunately,
a sample of 12ag was suitable to get the molecular structure from
single-crystal X-ray diffraction analysis confirming the supposed
constitution.17 The strongly electron-withdrawing nitro group of
11c may have a dominating electronic influence on the nucleo-
philicity of the imidazole nitrogen atoms, which is different to the
steric effect and overcompensates the latter. But also in the case of
12ac, single-crystal X-ray diffraction analysis verified the assumed
structure as shown in Figure 1.18 Thus, we presume that the steri-
cally less hindered nitrogen atom of 11b, 11c, and 11g will generally
be favored to attack the allenyl isothiocyanate 2.
13ab R1 = H
13db R1 = CH2OMe
Scheme 5.
Treatment of cumulene 2 with azoles 11 did not only afford the
aromatic heterocycles 12 but also the 5-methylenethiazole
derivatives 13. In the case of 13bd and 13df, these non-aromatic
thiazoles represent even the main products as depicted in Table 1.
Although all compounds 13 are stable at ꢁ18 ꢀC for several months,
they were converted quantitatively into the more favorable aro-
matic tautomers 12 in the presence of chloroform, for example,
when 13 was stored in CDCl3 solution in an NMR tube.19 The rate of
this isomerization was found to be concentration dependent. Sep-
aration of 12 and 13 by flash chromatography using silica gel was
also accompanied by the rearrangement to 12, thus hampering the
isolation of 13. On the other hand, the directed aromatization 13/
12 led to uniform products. Furthermore, this reaction confirmed
that only the less sterically hindered nitrogen atom of 11b attacked
the allenyl isothiocyanates 2 to form the products 13ab and 13db.
R1
C
NCS
2a,d
N
+
2'
1'
N
N
11g
H
NO2
N
attack
of N-2'
attack
of N-1'
N
N
S
R1
Me
R1
Me
Me
12ac
N
N
N
N
N
N
N
N
S
S
12ag R1 = H
12dg R1 = CH2OMe
14
Scheme 4.
Figure 1. Molecular structure of 12ac.

B. Jawabrah Al-Hourani et al. / Tetrahedron 64 (2008) 5590–5597
5593
3. Conclusion
and the residue was purified by column chromatography (silica gel,
50ꢂ3 cm) using CH2Cl2/Et2O (1:1) to reveal the products in the
order 7, 6, and 5.
A new family of substituted thiazoles bearing different types of
azole heterocycles at C-2 position was prepared via the reaction of
these heterocycles with highly reactive allenyl isothiocyanates. The
steric as well as the electronic effects of the azole nucleophiles
controlled the position of the introduced thiazole ring. The result-
ing heterocyclic products may have biological activities and will be
subjected to further studies.
4.3.1. 5-Methyl-3H-thiazol-2-one (5)
Yield: 0.49 g, 4.3 mmol, 4%, colorless solid; ꢁm1p 137–138 ꢀC (lit.11
144–145 ꢀC), IR (CDCl3): 3160, 1690, 1660 cm
.
1H NMR (CDCl3):
d¼2.12 (d, 4J¼1.5 Hz, 3H, CH3), 6.28 (q, 4J¼1.5 Hz, 1H, H-4), 10.19 (br,
1H, NH). 13C NMR (CDCl3): d¼13.7 (q), 116.3 (s), 116.4 (d), 176.1 (s).
MS, m/z (%) 115 (100) [M]þ, 60 (49), 59 (84), 58 (19), 45 (22).
4. Experimental
4.1. General
4.3.2. Bis(5-methylthiazol-2-yl) sulfide (6)
Yield: 3.41 g, 15.0 mmol, 43.5%, colorless solid; mp: 51 ꢀC. 1H
NMR (CDCl3): d¼2.42 (d, 4J¼1.2 Hz, 3H, CH3), 7.44 (q, 4J¼1.2 Hz, 1H,
H-4). 13C NMR (CDCl3): d¼11.98 (q, CH3), 138.22 (s, C-5), 141.45 (d,
C-4), 156.63 (s, C-2). MS, m/z (%) 228 (100) [M]þ, 86 (57), 72 (70), 71
(70), 59 (56). Anal. Calcd for C8H8N2S3 (228.35): C, 42.08; H, 3.53; N,
12.27; S, 42.12. Found: C, 41.97; H, 3.47; N, 12.20; S, 42.23.
1H NMR spectra were recorded at 300 MHz, 13C NMR spectra at
75 MHz, and 15N NMR spectra at 40 MHz. Chemical shifts (d) are
reported in parts per million (ppm) downfield from TMS. Coupling
constants (J) are reported in hertz (Hz) and spin multiplicities are
indicated by the following symbols: s (singlet), d (doublet), t
(triplet), q (quartet), m (multiplet). Infrared spectra were recorded
as solutions in CDCl3. TLC was performed on Macherey–Nagel
precoated silica gel Polygram Sil G/UV254 plates and viewed by UV.
Flash chromatography20 was carried out on Fluka silica gel 60. HPLC
separations were conducted under isocratic flow with distilled and
degassed diethyl ether. A Knauer model 64 HPLC pump equipped
with Merck LiChrospher Si 60, 5 mm (B 20 mm, l¼20 cm) column,
and UV detector (l¼254 nm) was utilized. For elemental analyses,
Vario El (Elementar Analysensystem GmbH) was employed. MS
data (70 eV, electron impact) resulted from Hewlett–Packard
spectrometer 5988 A. Mariner 5229 from Applied Biosystems was
used for HRMS utilizing the method of electrospray ionization.
Warning. In the case of unstable allenyl isothiocyanates 2, it was
useful to minimize polymerization by dilution of the collected
substance with a weighed quantity of an inert solvent before
thawing the trap.5c,d Otherwise, a dangerously vigorous reaction is
possible since undiluted allenyl isothiocyanates, especially 2a, tend
to spontaneous strongly exothermic polymerization at rt. Some of
the reactions of 2 with nucleophiles are also highly exothermic. If
the evolution of heat was not known, the addition of the reagent
was performed dropwise while the other reaction partner was
stirred with cooling.
4.3.3. (5,50-Dimethyl-[2,30-bithiazolyl]-20-ylidene)-(5-methyl-
thiazol-2-yl)-amine (7)
Yield: 1.81 g, 5.90 mmol, 23%, yellow solid; mp: 180 ꢀC. 1H NMR
(CDCl3): d¼2.42 (d, 4J¼1.5 Hz, 3H, CH3), 2.40 (d, 4J¼1.2 Hz, 3H, CH3),
2.43 (d, 4J¼1.2 Hz, 3H, CH3), 7.15 (q, 4J¼1.2 Hz, 1H, ]CH), 7.17 (q,
4J¼1.2 Hz, 1H, ]CH), 7.65 (q, 4J¼1.5 Hz, 1H, ]CH). 13C NMR (CDCl3):
d¼11.46 (q, CH3),12.32 (q, CH3),12.90 (q, CH3),118.20 (s, ]C),118.39
(d, ]CH), 128.12 (s, ]C), 130.14 (s, ]C), 134.59 (d, ]CH), 136.19 (d,
]CH), 154.26 (s, N]C), 154.35 (s, N]C), 167.69 (s, N]C). 15N NMR
(DMSO-d6): d¼ꢁ218.60 (d, 2J¼4 Hz, N-2), ꢁ176.65 (s, N-3), ꢁ101.95
(d, 2J¼11 Hz, N-1 or N-4), ꢁ101.79 (d, 2J¼10 Hz, N-4 or N-1). MS, m/z
(%) 308 (100) [M]þ, 151 (18), 125 (17), 72 (22), 71 (27), 59 (22). Anal.
Calcd for C12H12N4S3 (308.43): C, 46.73; H, 3.92; N, 18.17; S, 31.18.
Found: C, 46.71; H, 4.05; N, 17.98; S, 31.05. We do not have direct
evidence for the (Z)-stereochemistry of 7 (Scheme 2). But intra-
molecular steric hindrance should be highly unfavorable in (E)-7.
Furthermore, we were able to verify (Z)-stereochemistry by single-
crystal X-ray diffraction analysis in the case of a similar compound.8
4.4. Reaction of isothiocyanatopropa-1,2-diene (2a) with
hydrogen sulfide
To a solution of hydrogen sulfide in water (142 mL, 0.0725 M,
titrated with NaOH) and THF (284 mL), isothiocyanatopropa-1,2-
diene (2a) (1.99 g, 20.5 mmol) was added and the mixture was
stirred for 8 days at rt. Thereafter, THF was removed under vacuum,
and the residue was extracted with CH2Cl2, dried (MgSO4), and
concentrated to afford bis(5-methylthiazol-2-yl) sulfide (6) (1.81 g,
7.9 mmol, 77%).
4.2. Flash vacuum pyrolysis of 1-methoxy-4-thiocyanatobut-
2-yne (1d) to generate 3-isothiocyanato-4-methoxybuta-1,2-
diene (2d)
The flash vacuum pyrolysis21 of 1-methoxy-4-thiocyanatobut-
2-yne7 (1d) (0.10 g, 0.71 mmol) was performed at 400 ꢀC and
10ꢁ5 Torr (vaporization temperature: 70–80 ꢀC) to give a mixture of
1d and 3-isothiocyanato-4-methoxybuta-1,2-diene (2d) (0.095 g,
0.674 mmol, 95%) with thermal equilibrium ratio of 4% and 96% of
1d and 2d, respectively. The unstable allenyl isothiocyanate 2d was
separated by flash chromatography using n-hexane and diethyl
ether (7:3). The following flash vacuum pyrolysis of pure 2d at
400 ꢀC and 10ꢁ5 Torr yielded a mixture of 1d and 2d with the same
4.5. Reaction of isothiocyanatopropa-1,2-diene (2a) with
5-methyl-3H-thiazole-2-thione (8)
To a solution of 5-methyl-3H-thiazole-2-thione (8)12 (2.70 g,
20.6 mmol) in THF (100 mL), H2O (50 mL) was added followed
by the addition of isothiocyanatopropa-1,2-diene (2a) (2.00 g,
20.6 mmol). After stirring for 14 days at rt, THF was removed under
vacuum and the residue was extracted with CH2Cl2, dried (MgSO4),
and concentrated to reveal bis(5-methylthiazol-2-yl) sulfide (6)
(4.86 g, 20.5 mmol, 99.6%).
ratio of 4:96, respectively. IR (CDCl3): 2007 (NCS) cmꢁ1 1H NMR
.
(CDCl3): d¼3.35 (s, 3H, OCH3), 4.05 (t, 5J¼2.1 Hz, 2H, OCH2), 5.34 (t,
5J¼2.2 Hz, 2H, ]CH2). 13C NMR (CDCl3): d¼57.64 (q, OCH3), 72.31 (t,
OCH2), 84.58 (t, C-1), 101.67 (s, C-3), 139.20 (s, NCS), 206.80 (s, C-2).
4.3. Reaction of isothiocyanatopropa-1,2-diene (2a) with
water
4.6. Reaction of isothiocyanatopropa-1,2-diene (2a) with
aqueous ammonia
To H2O (250 mL) and THF (500 mL), isothiocyanatopropa-
1,2-diene (2a) (10.0 g, 103.1 mmol) was added, and the mixture was
stirred for 21 h at rt. The solvents were removed at 50 ꢀC/26 mbar,
To a mixture of aqueous ammonia (85 mL, 11.6 mmol, 0.137 M)
and THF (170 mL), isothiocyanatopropa-1,2-diene (2a) (5.04 g,
52.0 mmol) was added and the solution was stirred for 10 days at rt.

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B. Jawabrah Al-Hourani et al. / Tetrahedron 64 (2008) 5590–5597
Then, THF was removed under vacuum and the residue was
extracted with CH2Cl2, dried (MgSO4), and concentrated. The crude
product was recrystallized from Et2O/CH2Cl2 to furnish (5,50-
dimethyl-[2,30-bithiazolyl]-20-ylidene)-(5-methylthiazol-2-yl)-
amine (7) (3.15 g, 10.2 mmol, 88%).
When the reaction of 2a with aqueous ammonia was performed
similarly but using a smaller amount of 2a (3.14 g, 32.4 mmol
instead of 5.04 g), analogous work-up gave 7 (1.65 g, 50%), 913
(0.41 g, 11%), and 10 (0.76 g, 22%). Compound 10 could be enriched
by chromatography to afford a yellow solid. However, we were not
able to separate it from the other products completely.
Compound 12ba. Mp: 31–32 ꢀC. 1H NMR (CDCl3): d¼1.28 (t,
3J¼7.5 Hz, 3H, CH3), 2.80 (q, 3J¼7.5 Hz, 2H, CH2), 7.11 (d, 4J¼1.2 Hz,
1H, ]CH), 7.19 (d, 3J¼1.2 Hz, 1H, ]CH), 7.41 (t, 4J¼1.5 Hz, 1H, ]CH),
8.06 (s, 1H, ]CH). 13C NMR (CDCl3): d¼15.61 (q), 20.41 (t), 117.41
(d), 130.41 (d), 135.17 (d), 135.86 (d), 138.44 (s), 155.11 (s). Anal.
Calcd for C8H9N3S (179.24): C, 53.61; H, 5.06; N, 23.44; S, 17.89.
Found: C, 53.22; H, 5.04; N, 23.35; S, 17.63.
Compound 13ba. Mp: 56–57 ꢀC. 1H NMR (CDCl3): d¼1.73 (dt,
3J¼6.6 Hz, 5J¼2.4 Hz, 3H, CH3), 4.89 (m, 2H, CH2), 5.64 (qt,
3J¼6.6 Hz, 4J¼2.4 Hz, 1H, ]CH–CH3), 7.09 (d, 3J¼1.2 Hz, 1H, ]CH),
7.49 (d, 3J¼1.2 Hz, 1H, ]CH), 7.99 (s, 1H, ]CH). 13C NMR (CDCl3):
d¼18.21 (q), 66.09 (t), 115.79 (d), 117.51 (d), 130.53 (d), 136.21 (d),
137.25 (s), 151.31 (s). ESI-MS (m/z) calcd for C8H9N3S [MþH]þ:
180.0590. Found: 180.0560. We do not have direct evidence for the
(Z)-stereochemistry of 13ba, see Table 1. But in the case of similar
compounds,5c we were able to verify this stereochemistry by 1H
NMR NOE experiments.
4.6.1. 5,50-Dimethyl-20-imino-[2,30-bithiazolyl] (10)
1H NMR (CDCl3): d¼2.14 (d, 4J¼1.6 Hz, 3H, CH3), 2.42 (d,
4J¼1.3 Hz, 3H, CH3), 7.13 (q, 4J¼1.3 Hz, 1H, ]CH), 7.34 (q, 4J¼1.6 Hz,
1H, ]CH), 7.70 (br s, 1H, NH). 13C NMR (CDCl3): d¼11.32 (q, CH3),
13.19 (q, CH3), 113.77 (s), 119.27 (d), 128.49 (s), 134.26 (d), 154.47 (s),
159.87 (s). MS, m/z (%) 211 (100) [M]þ, 170 (36), 125 (32), 99 (71), 71
(35), 59 (59).
4.8.3. 2-Imidazol-1-yl-4,5-dimethylthiazole 12ca
Yield: 0.59 g (80%), yellow crystals; mp: 62–63 ꢀC (from diethyl
ether). 1H NMR (CDCl3): d¼2.29 (s, CH3), 2.34 (s, CH3), 7.13 (d,
3J¼0.9 Hz, 1H, ]CH), 7.41 (d, 3J¼0.9 Hz, 1H, ]CH), 8.07 (s, 1H,
]CH). 13C NMR (CDCl3): d¼11.18 (q, CH3), 14.61 (q, CH3), 117.44 (d),
122.97 (s), 130.50 (d), 135.22 (d), 145.82 (s), 152.62 (s). Anal. Calcd
for C8H9N3S (179.24): C, 53.60; H, 5.06; N, 23.44; S, 17.88. Found: C,
53.20; H, 5.23; N, 23.34; S, 17.67.
4.7. Reaction of isothiocyanatopropadiene (2a) with 9
To a solution of 913 (1.18 g, 10.3 mmol) in THF (100 mL), water
(50 mL) and isothiocyanatopropadiene (2a) (2.00 g, 20.6 mmol)
were added. The mixture was stirred for 17 days at rt. After removal
of THF under vacuum, the residue was extracted with CH2Cl2, dried
(MgSO4), and concentrated to yield 7 (2.87 g, 90%).
4.8.4. 2-Imidazol-1-yl-4-methoxymethyl-5-methylthiazole (12da)
and 2-imidazol-1-yl-4-methoxymethyl-5-methylene-4,5-
dihydrothiazole (13da)
4.8. General procedure for the synthesis of thiazoles from
allenyl isothiocyanates 2 and azoles 11
Following the general procedure, thiazoles 12da (0.45 g,
2.15 mmol, 74%) and 13da (0.08 g, 0.383 mmol, 13%) were obtained
as white solid (recrystallization from acetone and n-hexane) and
yellow semi-solid, respectively.
Isothiocyanatopropa-1,2-diene 2a, 2b, 2c, or 2d (each 10% in dry
THF,1.50 equiv) was added to azoles 11a–n (1.00 equiv) dissolved in
5 mL of a dry appropriate solvent (for azoles 11a–m, see Table 1; for
azole 11n, see Scheme 3). After the reaction was completed, the
solvent was removed under vacuum. If necessary, the crude prod-
ucts were separated by flash chromatography using diethyl ether
for 12ca, acetone and n-hexane (3:7) for 12da/13da, acetone and
n-hexane (1:4) for 12ab/13ab and 12ac, acetone and n-hexane (2:3)
for 12db/13db, diethyl ether and n-hexane (2:3) for 12bd/13bd,
ethyl acetate and n-hexane (2:1) for 12cd, diethyl ether and
n-hexane (1:1) for 12dd, diethyl ether and n-hexane (1:4) for 12ae/
13ae, 12af/13af, and 12ak, ethyl acetate and n-hexane (3:7) for
12de/13de and 12df/13df, ethyl acetate and dichloromethane (3:7)
for 12ag and 12dg, ethyl acetate and dichloromethane (2:3) for
12dj/13dj, and finally acetone and n-hexane (1:2) for 12an/12an0.
Upon separation by flash chromatography, the non-aromatic
product was eluted before the aromatic one in all cases.
Compound 12da. Mp: 43–44 ꢀC. 1H NMR (CDCl3): d¼2.48 (s, 3H,
CH3), 3.44 (s, 3H, OCH3), 4.45 (s, 2H, OCH2), 7.16 (d, 3J¼0.9 Hz, 1H,
]CH), 7.45 (d, 3J¼0.9 Hz, 1H, ]CH), 8.12 (s, 1H, ]CH). 13C NMR
(CDCl3): d¼10.89 (q), 58.18 (q), 67.05 (t), 117.37 (d), 128.42 (s),
130.32 (d), 135.10 (d), 145.90 (s), 153.27 (s). Anal. Calcd for
C9H11N3OS (209.27): C, 51.65; H, 5.30; N, 20.08; S, 15.32. Found: C,
51.82; H, 5.28; N, 20.17; S, 15.21.
Compound 13da. 1H NMR (CDCl3): d¼3.43 (s, 3H, O–CH3), 3.78
(m, 2H, O–CH2, diastereotopic protons), 5.18 (m, 1H, CH), 5.43 (m,
2H, ]CH2, non-equivalent protons), 7.11 (dd, 4J¼0.9 Hz, 3J¼1.5 Hz,
1H, ]CH), 7.26 (d, 4J¼0.9 Hz, 1H, ]CH), 7.43 (t, 3J¼1.5 Hz, 1H,
]CH). 13C NMR (CDCl3): d¼59.17 (q), 75.10 (t), 77.37 (d), 106.89 (t),
117.39 (d), 130.23 (d), 135.99 (d), 146.24 (s), 150.79 (s). ESI-MS (m/z)
calcd for C9H11N3OS [MþH]þ: 210.0696. Found: 210.0637.
4.8.1. 2-Imidazol-1-yl-5-methylthiazole (12aa)
4.8.5. 2-(2-Ethyl-4-methylimidazole-1-yl)-5-methylthiazole (12ab)
and 2-(2-ethyl-4-methylimidazol-1-yl)-5-methylene-
4,5-dihydrothiazole (13ab)
Following the general procedure, thiazoles 12ab (0.63 g,
3.04 mmol, 80%) and 13ab (0.08 g, 0.386 mmol, 10%) were obtained
as yellow oils.
Yield: 0.66 g (80%), yellow crystals; mp: 59–60 ꢀC (from
acetone). 1H NMR (CDCl3): d¼2.47 (d, 4J¼1.2 Hz, 3H, CH3), 7.15 (d,
3J¼0.9 Hz, 1H, CH), 7.21 (d, 3J¼0.9 Hz, 1H, ]CH), 7.44 (q, 4J¼1.2 Hz,
1H, H-4), 8.09 (s, 1H, H-20). 13C NMR (CDCl3): d¼11.88 (q, CH3),
117.44 (d, C]CH), 130.53 (d, C]CH), 130.73 (s, C-5), 135.18 (d,
C]CH), 137.53 (d, C]CH), 155.31 (s, C-2). Anal. Calcd for C7H7N3S
(165.22): C, 50.88; H, 4.27; N, 25.43; S, 19.40. Found: C, 50.39; H,
4.05; N, 25.44; S, 19.23.
Compound 12ab. 1H NMR (CDCl3): d¼1.28 (t, 3J¼7.5 Hz, 3H, CH3),
2.19 (d, 4J¼1.2 Hz, 3H, CH3), 2.43 (d, 4J¼1.2 Hz, 3H, CH3), 2.94 (q,
3J¼7.5 Hz, 2H, CH2), 6.91 (q, 4J¼1.2 Hz, 1H, ]CH), 7.21 (q, 4J¼1.2 Hz,
1H, ]CH). 13C NMR (CDCl3): d¼11.90 (q), 11.98 (q), 13.33 (q), 21.76
(t), 115.77 (d), 131.83 (s), 137.23 (s), 137.56 (d), 149.41 (s), 155.74 (s).
ESI-MS (m/z) calcd for C10H13N3OS [MþH]þ: 208.0851. Found:
208.0822.
4.8.2. 5-Ethyl-2-imidazol-1-yl-thiazole (12ba) and 5-ethylidene-2-
imidazol-1-yl-4,5-dihydrothiazole (13ba)
Following the general procedure, thiazoles 12ba (0.50 g,
2.79 mmol, 56%) and 13ba (0.22 g, 1.23 mmol, 25%) were separated
by HPLC and obtained as yellow oils. Compound 12ba was recrys-
tallized from n-pentane whereas thiazole 13ba was recrystallized
from n-hexane.
Compound 13ab. 1H NMR (CDCl3): d¼1.27 (t, 3J¼7.5 Hz, 3H, CH3),
2.15 (d, 4J¼1.2 Hz, 3H, CH3), 2.95 (q, 3J¼7.5 Hz, 2H, CH2), 4.95 (t,
4J¼3.0 Hz, 2H, ]CH2), 5.25 (m, 2H, CH2), 6.75 (q, 4J¼1.2 Hz, 1H,
]CH). 13C NMR (CDCl3): d¼11.77 (q), 13.27 (q), 21.85 (t), 68.11 (t),

B. Jawabrah Al-Hourani et al. / Tetrahedron 64 (2008) 5590–5597
5595
104.58 (t), 115.09 (d), 137.14 (s), 146.26 (s), 150.73 (s), 151.83 (s).
ESI-MS (m/z) calcd for C10H13N3OS [MþH]þ: 208.0903. Found:
208.0890.
142.76 (d), 164.34 (s). ESI-MS (m/z) calcd for C8H9N3S [MþH]þ:
180.0590. Found: 180.0648. For the stereochemistry of 13bd, see
the statement on that of 13ba.
4.8.6. 2-(2-Ethyl-4-methylimidazol-1-yl)-4-methoxymethyl-5-
methylthiazole (12db) and 2-(2-ethyl-4-methylimidazol-1-yl)-4-
methoxymethyl-5-methylene-4,5-dihydrothiazole (13db)
Following the general procedure, thiazoles 12db (0.90 g,
3.59 mmol, 79%) and 13db (0.03 g, 0.136 mmol, 3%) were obtained
as orange and yellow oils, respectively.
4.8.10. 4,5-Dimethyl-2-pyrazol-1-ylthiazole (12cd)
Yield: 0.57 g (77%), white solid; mp: 64–65 ꢀC (from diethyl
ether and n-hexane). 1H NMR (CDCl3): d¼2.21 (s, 3H, CH3), 2.25 (s,
3H, CH3), 6.35 (dd, 3J¼2.4, 1.2 Hz, 1H, ]CH), 7.60 (d, 3J¼1.2 Hz, 1H,
]CH), 8.26 (d, 3J¼2.4 Hz, 1H, ]CH). 13C NMR (CDCl3): d¼11.20 (q),
14.70 (q), 108.11 (d), 122.85 (s), 126.73 (d), 142.12 (d), 144.99 (s),
156.87 (s). Anal. Calcd for C8H9N3S (179.24): C, 53.61; H, 5.06; N,
23.44; S, 17.89. Found: C, 53.10; H, 5.19; N, 23.19; S, 17.91.
Compound 12db. IR (CDCl3): 1588 (C]C), 1401 (C]N), 1334
(S–C),1070 (C–O–C) cmꢁ1. 1H NMR (CDCl3): d¼1.21 (t, 3J¼7.5 Hz, 3H,
4
CH2CH3), 2.10 (s, 3H, Me-5), 2.36 (d, J¼1.2 Hz, 3H, Me-40), 2.85 (q,
3J¼7.5 Hz, 2H, CH2CH3), 3.32 (s, 3H, OMe), 4.36 (s, 2H, OCH2), 6.86
(q, 4J¼1.2 Hz, 1H, H-50). 13C NMR (CDCl3): d¼10.74 (q, Me), 11.73 (q,
Me), 13.12 (q, Me), 21.54 (t, CH2CH3), 58.02 (q, OMe), 67.16 (t, OCH2),
115.53 (d, C-50), 129.51 (s), 136.92 (s), 145.82 (s), 149.07 (s), 153.40
(s). Anal. Calcd for C12H17N3OS (251.35): C, 57.34; H, 6.82; N, 16.72;
S, 12.76. Found: C, 57.12; H, 6.63; N, 16.50; S, 12.69.
4.8.11. 4-Methoxymethyl-5-methyl-2-pyrazol-1-ylthiazole (12dd)
Yield: 0.42 g (91%), pale yellow oil. 1H NMR (CDCl3): d¼2.44 (s,
3H, CH3), 3.42 (s, 3H, OCH3), 4.43 (s, 2H, OCH2), 6.42 (t, 3J¼2.4 Hz,
1H, ]CH), 7.67 (d, 3J¼1.5 Hz, 1H, ]CH), 8.31 (d, 3J¼2.4 Hz, 1H,
]CH). 13C NMR (CDCl3): d¼11.11 (q), 58.26 (q), 67.42 (t), 108.24 (d),
126.06 (d), 128.45 (s), 142.31 (d), 145.36 (s), 157.76 (s). Anal. Calcd
for C9H11N3OS (209.27): C, 51.65; H, 5.30; N, 20.08; S, 15.32. Found:
C, 51.75; H, 5.53; N, 20.11; S, 15.29.
Compound 13db. IR (CDCl3): 1640 (C]C), 1401 (C]N), 1292 (S–C),
1072 (C–O–C) cmꢁ1.1HNMR(CDCl3): d¼1.26 (t, 3J¼7.5 Hz, 3H, CH2CH3),
4
2.13 (d, J¼1.2 Hz, 3H, Me-40), 2.97 (m, 2H, CH2CH3, diastereotopic
protons), 3.38 (s, 3H, OMe), 3.62 (m, 2H, OCH2, diastereotopic protons),
4.8.12. 2-(3,5-Dimethylpyrazol-1-yl)-5-methylthiazole (12ae)
and 2-(3,5-dimethylpyrazol-1-yl)-5-methylene-4,5-dihydro-
thiazole (13ae)
Following the general procedure, thiazoles 12ae (0.50 g,
2.58 mmol, 49%) and 13ae (0.33 g, 1.70 mmol, 33%) were obtained
as yellow oil and white solid (recrystallization from n-hexane),
respectively.
4
5.14 (m, 1H), 5.34 (m, 2H), 6.75 (q, J¼1.2 Hz, 1H, H-50). 13C NMR
(CDCl3): d¼11.80 (q, Me), 13.30 (q, Me), 22.29 (t, CH2CH3), 59.44 (q,
OMe), 75.46 (t, OCH2), 78.42 (d, C-4), 106.23 (t, ]CH2), 115.19 (d, C-50),
137.21 (s), 147.41 (s), 150.91 (s), 151.65 (s). ESI-MS (m/z) calcd for
C
12H17N3OS [MþH]þ: 252.1165. Found: 252.1184.
4.8.7. 5-Methyl-2-(4-nitroimidazol-1-yl)thiazole (12ac)
Compound 12ae. IR (CDCl3): 1573 (C]C), 1442 (C]N), 1262
(S–C) cmꢁ1. 1H NMR (CDCl3): d¼2.26 (s, 3H, Me), 2.41 (d, 4J¼1.2 Hz,
3H, 5-Me), 2.61 (s, 3H, Me), 5.95 (s, 1H, H-40), 7.13 (q, 4J¼1.2 Hz, 1H,
H-4). 13C NMR (CDCl3): d¼11.77 (q, Me), 13.45 (q, Me), 13.50 (q, Me),
109.06 (d, C-40), 129.78 (s), 137.01 (d, C-4), 141.14 (s), 150.96 (s),
160.56 (s). Anal. Calcd for C9H11N3S (193.27): C, 55.93; H, 5.74; N,
21.74. Found: C, 55.77; H, 5.83; N, 21.55.
Compound 13ae. Mp: 75–76 ꢀC. IR (CDCl3): 1573 (C]C), 1440
(C]N), 1265 (S–C) cmꢁ1. 1H NMR (CDCl3): d¼2.23 (s, 3H, Me), 2.53
(s, 3H, Me), 5.02 (t, 4J¼2.7 Hz, 2H, H-4), 5.22 (m, 2H, ]CH2), 5.95 (s,
1H, H-40). 13C NMR (CDCl3): d¼13.52 (q, Me), 13.83 (q, Me), 68.55 (t,
C-4), 103.11 (t, ]CH2), 110.00 (d, C-40), 142.55 (s), 146.89 (s), 151.35
(s), 156.69 (s). Anal. Calcd for C9H11N3S (193.27): C, 55.93; H, 5.74;
N, 21.74; S, 16.59. Found: C, 55.91; H, 5.76; N, 21.58; S, 16.98.
Yield: 0.63 g (68%), white solid; mp: 148–150 ꢀC (from diethyl
ether). IR (CDCl3): 1554 (C]C), 1517 (NO2), 1401 (C]N), 1228
(S–C) cmꢁ1. 1H NMR (CDCl3): d¼2.52 (d, 4J¼1.5 Hz, 3H, Me), 7.32 (q,
4
4J¼1.5 Hz, 1H, H-4), 8.05 (d, J¼1.5 Hz, 1H, H-20 or H-50), 8.25 (d,
4J¼1.5 Hz, 1H, H-50 or H-20). 13C NMR (CDCl3): d¼12.07 (q, Me),
116.85 (d), 133.56 (s), 133.70 (d), 138.37 (d), 148.62 (s), 152.77 (s).
Anal. Calcd for C7H6N4O2S (242.22): C, 39.99; H, 2.88; N, 26.65; S,
15.25. Found: C, 40.23; H, 2.86; N, 26.58; S, 15.26.
4.8.8. 5-Methyl-2-pyrazol-1-ylthiazole (12ad)
Yield: 0.74 g (90%), yellow crystals; mp: 47–48 ꢀC (from diethyl
ether). 1H NMR (CDCl3): d¼2.45 (d, 4J¼1.2 Hz, 3H, CH3), 6.44 (dd,
3J¼2.61, 1.8 Hz, 1H, ]CH), 7.17 (q, 4J¼1.2 Hz, 1H, Th–H-4), 7.68 (dd,
3J¼1.8 Hz, 4J¼0.6 Hz, 1H, ]CH), 8.28 (dd, 3J¼2.7 Hz, 4J¼0.6 Hz, 1H,
]CH). 13C NMR (CDCl3): d¼12.00 (q, CH3), 108.32 (d, C]CH), 126.84
(d), 130.62 (s, C-5), 137.06 (d, C]CH), 142.26 (d, C]CH), 159.65 (s,
C-2). Anal. Calcd for C7H7N3S (165.22): C, 50.88; H, 4.27; N, 25.43; S,
19.40. Found: C, 50.62; H, 4.02; N, 25.43; S, 19.16.
4.8.13. 2-(3,5-Dimethylpyrazol-1-yl)-4-methoxymethyl-5-
methylthiazole (12de) and 2-(3,5-dimethylpyrazol-1-yl)-4-
methoxymethyl-5-methylene-4,5-dihydrothiazole (13de)
Following the general procedure, thiazoles 12de (0.61 g,
2.57 mmol, 50%) and 13de (0.37 g, 1.56 mmol, 30%) were obtained
as colorless oils.
Compound 12de. IR (CDCl3): 1573 (C]C), 1412 (C]N), 1365
(S–C), 1083 (C–O–C) cmꢁ1. 1H NMR (CDCl3): d¼2.25 (s, 3H, Me), 2.42
(s, 3H, Me), 2.63 (s, 3H, Me), 3.41 (s, 3H, OMe), 4.43 (s, 2H, OCH2),
5.94 (s, 1H, H-40). 13C NMR (CDCl3): d¼10.44 (q, Me), 13.15 (q, Me),
13.16 (q, Me), 57.70 (q, OMe), 67.30 (t, OCH2), 108.71 (d, C-40), 127.44
(s), 140.87 (s), 145.09 (s), 150.54 (s), 158.06 (s). Anal. Calcd for
4.8.9. 5-Ethyl-2-pyrazol-1-ylthiazole (12bd) and 5-ethylidene-2-
pyrazol-1-yl-4,5-dihydrothiazole (13bd)
Following the general procedure, thiazoles 12bd (0.17 g,
0.950 mmol, 19%) and 13bd (0.24 g, 1.34 mmol, 27%) were obtained
as yellow oils.
Compound 12bd. 1H NMR (CDCl3): d¼1.32 (t, 3J¼7.5 Hz, 3H, CH3),
2.83 (q, 3J¼7.5 Hz, 2H, CH2), 6.44 (dd, 3J¼2.7, 1.8 Hz, 1H, ]CH), 7.19
(t, 4J¼1.2 Hz, 1H, thiazole ]CH), 7.68 (d, 3J¼1.8 Hz, 1H, ]CH), 8.27
(dd, 3J¼2.7 Hz, 4J¼0.6 Hz, 1H, ]CH). 13C NMR (CDCl3): d¼15.76 (q),
20.52 (t), 108.28 (d), 126.81 (d), 135.42 (d), 138.33 (s), 142.23 (d),
159.43 (s). Anal. Calcd for C8H9N3S (179.24): C, 53.61; H, 5.06; N,
23.44; S, 17.89. Found: C, 53.54; H, 5.11; N, 23.67; S, 17.78.
Compound 13bd. 1H NMR (CDCl3): d¼1.74 (dt, 3J¼6.9 Hz,
5J¼2.4 Hz, 3H, CH3), 4.96 (m, 2H, CH2), 5.61 (qt, 3J¼6.6 Hz,
4J¼2.4 Hz, 1H, ]CH–CH3), 6.45 (d, 3J¼2.1 Hz, 1H, ]CH), 7.70 (d,
3J¼2.1 Hz, 1H, ]CH), 8.28 (t, 3J¼2.1 Hz, 1H, ]CH); 13C NMR (CDCl3):
d¼17.94 (q), 66.51 (t), 109.68 (d), 114.64 (d), 127.81 (d), 138.03 (s),
C11H15N3OS (237.33): C, 55.67; H, 6.37; N, 17.71; S, 13.51. Found: C,
55.47; H, 6.37; N, 17.58; S, 13.68.
Compound 13de. IR (CDCl3): 1573 (C]C),1412 (C]N),1365 (S–C),
1084 (C–O–C) cmꢁ1. 1H NMR (CDCl3): d¼2.22 (s, 3H, Me), 2.54 (s, 3H,
Me), 3.42 (s, 3H, OMe), 3.62 (m, 2H, OCH2, diastereotopic protons),
5.19 (m,1H, CH), 5.31 (m, 2H), 5.94 (s,1H). 13C NMR (CDCl3): d¼13.50
(q, Me),13.92 (q, Me), 59.44 (q, OMe), 76.02 (t, OCH2), 78.75 (d, C-4),
104.81 (t, ]CH2), 110.03 (d, C-40), 142.74 (s), 147.79 (s), 151.47 (s),
156.23 (s). Anal. Calcd for C11H15N3OS (237.33): C, 55.67; H, 6.37; N,
17.71; S, 13.51. Found: C, 55.37; H, 6.31; N, 17.59; S, 13.91.

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4.8.14. 5-Methyl-2-(3,4,5-trimethylpyrazol-1-yl)thiazole (12af)
and 5-methylene-2-(3,4,5-trimethylpyrazol-1-yl)-4,5-dihydro-
thiazole (13af)
Following the general procedure, thiazoles 12af (0.62 g,
3.00 mmol, 66%) and 13af (0.21 g, 1.00 mmol, 22%) were obtained
as white solids (recrystallization from n-hexane).
C) cmꢁ1. 1H NMR (CDCl3): d¼2.46 (s, 3H, Me), 3.44 (s, 3H, OMe), 4.44
(s, 2H, OCH2), 7.10 (d, 3J¼2.6 Hz, 1H, H-40), 7.25 (ddd, 3J¼7.7, 4.9 Hz,
4J¼1.3 Hz, 1H, H-5), 7.75 (ddd, 3J¼7.9, 7.7 Hz, 4J¼1.9 Hz, 1H, H-4),
8.06 (ddd, 3J¼7.9 Hz, 4J¼1.3 Hz, 5J¼1.0 Hz, 1H, H-3), 8.36 (d,
3J¼2.6 Hz, 1H, H-50), 8.64 (ddd, 3J¼4.9 Hz, 4J¼1.9 Hz, 5J¼1.0 Hz, 1H,
H-6). 13C NMR (CDCl3): d¼11.14 (q, 500-Me), 58.31 (q, OMe), 67.43 (t,
OCH2), 107.12 (d, C-40), 120.56 (d, C-3), 123.16 (d, C-5), 128.48 (d,
C-50), 128.68 (s), 136.64 (d, C-4), 145.47 (s), 149.37 (d, C-6), 150.96
(s), 154.20 (s), 157.58 (s), assignments by C–H shift correlation. Anal.
Calcd for C14H14N4OS (286.36): C, 58.72; H, 4.93; N, 19.57; S, 11.20.
Found: C, 58.49; H, 4.90; N, 19.42; S, 11.31.
Compound 12af. Mp: 82–83 ꢀC. IR (CDCl3): 1595 (C]C), 1449
(C]N), 1277 (S–C) cmꢁ1. 1H NMR (CDCl3): d¼1.94 (s, 3H, Me), 2.21
(s, 3H, Me), 2.40 (d, 4J¼1.3 Hz, 3H, Me), 2.55 (s, 3H, Me), 7.12 (q,
4J¼1.3 Hz, 1H, H-4). 13C NMR (CDCl3): d¼7.81 (q, Me), 11.77 (q, Me),
11.81 (q, Me), 12.02 (q, Me), 115.46 (s), 129.29 (s), 136.87 (d, C-4),
137.45 (s), 150.57 (s), 161.01 (s). Anal. Calcd for C10H13N3S (207.29):
C, 57.94; H, 6.32; N, 20.27; S, 15.47. Found: C, 57.73; H, 6.35; N,
19.96; S, 16.02.
Compound 13af. Mp: 72–73 ꢀC. IR (CDCl3): 1619 (C]C), 1432
(C]N), 1275 (S–C) cmꢁ1. 1H NMR (CDCl3): d¼1.91 (s, 3H, Me), 2.18
(s, 3H, Me), 2.46 (s, 3H, Me), 5.01 (t, 4J¼2.4 Hz, 2H), 5.21 (t, 4J¼2.4 Hz,
2H). 13C NMR (CDCl3): d¼7.73 (q, Me), 12.05 (q, Me), 12.10 (q, Me),
68.49 (t, C-4), 102.86 (t, ]CH2), 116.44 (s), 138.51 (s), 146.89 (s),
151.16 (s), 156.85 (s). Anal. Calcd for C10H13N3S (207.29): C, 57.94; H,
6.32; N, 20.27; S, 15.47. Found: C, 57.93; H, 6.25; N, 20.22; S, 15.59.
4.8.18. 1-(5-Methylthiazol-2-yl)-1H-benzimidazole (12ah)
Yield: 0.64 g (85%), brown crystals; mp: 88–90 ꢀC (from ace-
tone). 1H NMR (CDCl3): d¼2.44 (d, 4J¼1.2 Hz, 3H, CH3), 7.33 (q,
4J¼1.2 Hz, 1H, H-40), 7.35 (t, 3J¼7.5 Hz, 2H, 2ꢂ]CH), 7.81 (d,
3J¼7.5 Hz, 1H, ]CH), 7.97 (d, 3J¼7.5 Hz, 1H, ]CH), 8.43 (s, 1H, H-2).
13C NMR (CDCl3): d¼11.81 (q, CH3), 112.06 (d), 120.62 (d, C]CH),
123.70 (d, C]CH), 124.63 (d, C]CH), 130.17 (s), 131.59 (s), 137.29 (d,
C]CH), 140.81 (d, C]CH), 143.83 (s, C]C), 154.73 (s, C-20). Anal.
Calcd for C11H9N3S (215.28): C, 61.37; H, 4.21; N, 19.51; S, 14.90.
Found: C, 61.23; H, 4.05; N, 19.41; S, 15.39.
4.8.15. 4-Methoxymethyl-5-methyl-2-(3,4,5-trimethylpyrazol-1-
yl)thiazole (12df) and 4-methoxymethyl-5-methylene-2-(3,4,5-
trimethylpyrazol-1-yl)-4,5-dihydrothiazole (13df)
Following the general procedure, thiazoles 12df (0.44 g,
1.75 mmol, 39%) and 13df (0.52 g, 2.07 mmol, 46%) were obtained
as white solid (recrystallization from n-hexane) and colorless oil,
respectively.
Compound 12df. Mp: 79–80 ꢀC. IR (CDCl3): 1595 (C]C), 1431
(C]N), 1363 (S–C), 1084 (C–O–C) cmꢁ1. 1H NMR (CDCl3): d¼1.89 (s,
3H, Me), 2.17 (s, 3H, Me), 2.37 (s, 3H, Me), 2.53 (s, 3H, Me), 3.38 (s,
3H, OMe), 4.39 (s, 2H, OCH2). 13C NMR (CDCl3): d¼7.67 (q, Me),10.70
(q, Me), 11.67 (q, Me), 11.89 (q, Me), 57.94 (q, OMe), 67.55 (t, OCH2),
115.26 (s), 127.18 (s), 137.39 (s), 145.08 (s), 150.40 (s), 158.68 (s).
Anal. Calcd for C12H17N3OS (251.35): C, 57.19; H, 6.83; N, 16.76; S,
13.03. Found: C, 57.16; H, 6.66; N, 16.81; S, 12.85.
Compound 13df. IR (CDCl3): 1638 (C]C), 1431 (C]N), 1363
(S–C), 1120 (C–O–C) cmꢁ1. 1H NMR (CDCl3): d¼1.84 (s, 3H, Me), 2.11
(s, 3H, Me), 2.42 (s, 3H, Me), 3.37 (s, 3H, OMe), 3.50 (m, 2H, OCH2,
diastereotopic protons), 5.12 (m, 1H), 5.24 (m, 2H). 13C NMR
(CDCl3): d¼7.42 (q, Me), 11.74 (q, Me), 11.94 (q, Me), 59.15 (q, OMe),
75.91 (t, OCH2), 78.41 (d, C-4), 104.28 (t, ]CH2), 116.23 (s), 138.37
(s), 147.70 (s), 150.94 (s), 156.12 (s). Anal. Calcd for C12H17N3OS
(251.35): C, 57.19; H, 6.83; N, 16.76; S, 13.03. Found: C, 57.34; H,
6.82; N, 16.72; S, 12.67.
4.8.19. 1-(5-Methylthiazol-2-yl)-1H-benzimidazol-
2-ylamine (12ai)
Yield: 0.34 g (83%), yellow crystals; mp: 173–175 ꢀC (from
diethyl ether). 1H NMR (DMSO-d6): d¼2.53 (d, 4J¼1.2 Hz, 3H, CH3),
7.02 (t, 3J¼6.6 Hz, 1H, ]CH), 7.12 (t, 3J¼6.6 Hz, 1H, ]CH), 7.24 (d,
3J¼6.6 Hz, 1H, ]CH), 7.35 (br, 2H, NH2), 7.45 (q, 4J¼1.2 Hz, 1H, H-40),
7.49 (d, 3J¼6.6 Hz, 1H, ]CH). 13C NMR (DMSO-d6): d¼11.54 (q, CH3),
109.33 (d, ]CH), 115.83 (d, ]CH), 119.68 (d, ]CH), 123.24 (d,
]CH), 130.34 (s, C]C), 131.36 (s, C]C), 136.63 (d, ]CH), 142.95 (s,
C]C), 153.37 (s), 155.35 (s). Anal. Calcd for C11H10N4S (230.22): C,
57.38; H, 4.34; N, 24.33; S, 13.93. Found: C, 56.94; H, 4.30; N, 24.25;
S, 14.00.
4.8.20. 2-Ethyl-1-(5-methylthiazol-2-yl)-1H-benzimidazole (12aj)
Yield: 1.00 g (82%), yellow crystals; mp: 56–57 ꢀC (from ace-
tone). 1H NMR (CDCl3): d¼1.40 (t, 3J¼7.8 Hz, 3H, CH3), 2.57 (d,
4J¼1.2 Hz, 3H, CH3 at C-50), 3.07 (q, 3J¼7.8 Hz, 2H, CH2), 7.29 (t, 3J¼
5.8 Hz, 2H, 2ꢂ]CH), 7.46 (q, 4J¼1.2 Hz, 1H, H-40), 7.53 (d, 3J¼5.8 Hz,
1H, ]CH), 7.77 (d, 3J¼5.8 Hz, 1H, ]CH). 13C NMR (CDCl3): d¼11.62
(q, CH3),12.24 (q, CH3), 21.88 (t, ethyl CH2),110.46 (d, C]CH),119.34
(d, C]CH), 123.25 (d, C]CH), 123.42 (d, C]CH), 134.48 (s, C]C),
135.40 (s, C]C), 138.23 (d, C]CH), 142.25 (s, C]C), 153.85 (s),
156.29 (s). Anal. Calcd for C13H13N3S (207.30): C, 64.16; H, 5.38; N,
17.26; S, 13.28. Found: C, 63.70; H, 5.41; N, 17.20; S, 13.64.
4.8.16. 2-[1-(5-Methylthiazol-2-yl)-1H-pyrazol-3-yl]-
pyridine (12ag)
4.8.21. 2-Ethyl-1-(4-methoxymethyl-5-methylthiazol-2-yl)-1H-
benzimidazole (12dj) and 2-ethyl-1-(4-methoxymethyl-5-
methylene-4,5-dihydrothiazol-2-yl)-1H-benzimidazole (13dj)
Following the general procedure, thiazoles 12dj (0.60 g,
2.09 mmol, 76%) and 13dj (0.13 g, 0.45 mmol,17%) were obtained as
yellow oils.
Compound 12dj. IR (CDCl3): 1613 (C]C), 1453 (C]N), 1364
(S–C),1075 (C–O–C) cmꢁ1. 1H NMR (CDCl3): d¼1.30 (t, 3J¼7.8 Hz, 3H,
CH2CH3), 2.39 (s, 3H, Me-50), 2.95 (q, 3J¼7.8 Hz, 2H, CH2CH3), 3.32 (s,
3H, OMe), 4.41 (s, 2H, OCH2), 7.14 (m, 2H, 2ꢂAr–H), 7.45 (m, 1H,
Ar–H), 7.64 (m, 1H, Ar–H). 13C NMR (CDCl3): d¼10.86 (q, Me), 11.20
(q, Me), 21.56 (t, CH2CH3), 57.96 (q, OMe), 67.05 (t, OCH2), 110.19 (d),
118.94 (d), 122.80 (d), 123.00 (d), 131.86 (s), 134.72 (s), 141.95 (s),
146.30 (s), 151.45 (s), 155.78 (s). Anal. Calcd for C15H17N3OS
(287.38): C, 62.69; H, 5.96; N, 14.62; S, 11.16. Found: C, 62.50; H,
5.78; N, 14.60; S, 11.62.
Yield: 0.45 g (91%), white solid; mp: 124–125 ꢀC (from diethyl
ether). IR (CDCl3): 1550 (C]C),1422 (C]N),1261 (S–C) cmꢁ1.1H NMR
(CDCl3): d¼2.45 (d, 4J¼1.3 Hz, 3H, Me), 7.10 (d, 3J¼3.0 Hz, 1H, H-40),
7.18 (q, 4J¼1.3 Hz, 1H, H-400), 7.24 (ddd, 3J¼7.5, 4.8 Hz, 4J¼1.2 Hz, 1H,
H-5), 7.74 (ddd, 3J¼7.8, 7.5 Hz, 4J¼1.7 Hz, 1H, H-4), 8.07 (ddd,
3J¼7.8 Hz, 4J¼1.2 Hz, 5J¼1.0 Hz,1H, H-3), 8.31 (d, 3J¼3.0 Hz,1H, H-50),
8.64 (ddd, 3J¼4.8 Hz, 4J¼1.7 Hz, 5J¼1.0 Hz,1H, H-6). 13C NMR (CDCl3):
d¼11.99 (q, 500-Me), 107.14 (d, C-40), 120.51 (d, C-3), 123.13 (d, C-5),
128.22 (d, C-50),130.79 (s, C-500), 136.57 (d, C-4), 137.17 (d, C-400),149.40
(d, C-6), 151.00 (s), 154.21 (s), 159.43 (s), assignments by C–H shift
correlation. Anal. Calcd for C12H10N4S (242.30): C, 59.48; H, 4.14; N,
22.93; S, 13.38. Found: C, 59.15; H, 4.15; N, 23.12; S, 13.23.
4.8.17. 2-[1-(4-Methoxymethyl-5-methylthiazol-2-yl)-1H-pyrazol-
3-yl]pyridine (12dg)
Yield: 0.52 g (88%), white solid; mp: 108–109 ꢀC (from n-hex-
ane). IR (CDCl3): 1545 (C]C), 1404 (C]N), 1366 (S–C), 1086 (C–O–
Compound 13dj. IR (CDCl3): 1615 (C]C),1456 (C]N),1364 (S–C),
1073 (C–O–C) cmꢁ1
.
1H NMR (CDCl3): d¼1.43 (t, 3J¼7.8 Hz, 3H,

B. Jawabrah Al-Hourani et al. / Tetrahedron 64 (2008) 5590–5597
5597
CH2Me), 3.14 (m, 2H, CH2Me, diastereotopic protons), 3.41 (s, 3H,
OMe), 3.75 (m, 2H, OCH2, diastereotopic protons), 5.27 (m, 1H,
H-40), 5.41 (dd, 4J¼2.5 Hz, 2J¼2.1 Hz, 1H, C]CH2), 5.47 (dd,
4J¼2.3 Hz, 2J¼2.1 Hz, 1H, C]CH2), 7.27 (m, 2H, 2ꢂAr–H), 7.72 (m,
2H, 2ꢂAr–H). 13C NMR (CDCl3): d¼11.61 (q, CH2Me), 22.59 (t,
CH2Me), 59.30 (q, OMe), 75.31 (t, OCH2), 77.14 (d, C-40), 106.54 (t,
]CH2), 112.10 (d), 119.29 (d), 123.41 (d, 2ꢂAr–C), 133.82 (s), 142.14
(s), 147.31 (s), 152.22 (s), 156.08 (s). Anal. Calcd for C15H17N3OS
(287.38): C, 62.69; H, 5.96; N, 14.62; S, 11.16. Found: C, 62.14; H,
6.04; N, 14.67; S, 11.52.
(166.21): C, 43.62; H, 3.05; N, 33.91; S, 19.53. Found: C, 43.28; H,
3.55; N, 33.75; S, 18.65.
Acknowledgements
B.J.A.-H. thanks the DAAD (Deutscher Akademischer Aus-
tauschdienst)fora Ph.D. fellowship.WeareindebtedtotheFonds der
ChemischenIndustrieandtheDeutscheForschungsgemeinschaftfor
continued financial support. We thank Prof. Dr. W. Thiel, Dr. M. Jia,
and Dr. Y. Sun for the starting material 11g.
4.8.22. 1-(5-Methylthiazol-2-yl)-1H-indazole (12ak)
Yield: 0.78 g (95%), white solid; mp: 138–140 ꢀC (from diethyl
ether and n-hexane). 1H NMR (CDCl3): d¼2.46 (d, 4J¼1.2 Hz, 3H,
CH3), 7.10 (d, 3J¼7.5 Hz, 1H, aromatic ]CH), 7.30 (q, 4J¼1.2 Hz, 1H,
thiazole ]CH), 7.33 (d, 3J¼7.5 Hz, 1H, aromatic ]CH), 7.69 (t,
3J¼7.5 Hz, 2H, two aromatic ]CH), 8.78 (d, 4J¼1.2 Hz, 1H, pyrazole
]CH). 13C NMR (CDCl3): d¼12.00 (q), 117.69 (d), 119.95 (d), 120.81
(d),122.33 (s),123.17 (d),127.92 (d), 132.64 (s), 137.78 (d),150.04 (s),
159.64 (s). Anal. Calcd for C11H9N3S (215.28): C, 61.37; H, 4.21; N,
19.51; S, 14.90. Found: C, 61.43; H, 4.20; N, 19.08; S, 14.51.
References and notes
1. Part 15 of the series ‘Rearrangement Reactions’. For part 14, see Ref. 5d.
2. Sharma, S. Sulfur Rep. 1989, 8, 327–454.
3. Drobnica, L.; Kristian, P.; Augustin, J. The Chemistry of Cyanates and their Thio
Derivatives; Patai, S., Ed.; Wiley: Chichester, UK, 1977; pp 1003–1221.
4. Hartmann, A. Methoden der Organischen Chemie (Houben–Weyl), 4th ed.;
Hagemann, H., Ed.; Thieme: Stuttgart, 1983; Vol. E 4, pp 834–883.
5. (a) Banert, K.; Hu¨ cksta¨dt, H.; Vrobel, K. Angew. Chem. 1992, 104, 72–74; Angew.
Chem., Int. Ed. Engl. 1992, 31, 90–92; (b) Banert, K. Liebigs Ann. Recl. 1997, 2005–
2018; (c) Banert, K.; Groth, S.; Hu¨cksta¨dt, H.; Lehmann, J.; Schlott, J.; Vrobel, K.
Synthesis 2002, 1423–1433; (d) Banert, K.; Jawabrah Al-Hourani, B.; Groth, S.;
Vrobel, K. Synthesis 2005, 2920–2926.
6. (a) Billeter, O. Ber. Dtsch. Chem. Ges. 1875, 8, 462–466; (b) Gerlich, G. Justus
Liebigs Ann. Chem. 1875, 178, 80–91; (c) Billeter, O. Helv. Chim. Acta 1925, 8, 337–
338; (d) Mumm, O.; Richter, H. Ber. Dtsch. Chem. Ges. 1940, 73, 843–860; (e)
DeWolfe, R. H.; Young, W. G. Chem. Rev. 1956, 56, 753–901, see p 856; (f) Smith,
P. A. S.; Emerson, D. W. J. Am. Chem. Soc. 1960, 82, 3076–3082; (g) Iliceto, A.;
Fava, A.; Mazzucato, U. Tetrahedron Lett. 1960, 27–35; (h) Emerson, D. W.;
Klapprodt Booth, J. J. Org. Chem. 1965, 30, 2480–2481; (i) Fava, A. Org. Sulfur
Compd. 1966, 2, 73–91; (j) Ferrier, R. J.; Vethaviyaser, N. J. Chem. Soc. C 1971,
1907–1913; (k) Guthrie, R. D.; Williams, G. J. J. Chem. Soc., Chem. Commun. 1971,
923–924; (l) Huber, S.; Stamouli, P.; Jenny, T.; Neier, R. Helv. Chim. Acta 1986, 69,
1898–1915; (m) Hansen, H.-J. Chimia 1999, 53, 163–173; (n) Hansen, H.-J.
Chimia 2000, 54, 105–119.
4.8.23. 1-(5-Methylthiazol-2-yl)-1H-1,2,3-triazole (12al)
Yield: 0.57 g (69%), yellow crystals; mp: 45–47 ꢀC (from
acetone). 1H NMR (CDCl3): d¼2.51 (d, 4J¼1.2 Hz, 3H, CH3), 7.32 (q,
4J¼1.2 Hz, 1H, H-40), 7.38 (d, 3J¼1.2 Hz, 1H, ]CH), 7.81 (d, 3J¼1.2 Hz,
1H, ]CH). 13C NMR (CDCl3): d¼11.72 (q, CH3), 120.94 (d), 132.94 (s,
C-50), 134.06 (d), 137.31 (d), 154.77 (s, C-20). Anal. Calcd for C6H6N4S
(166.21): C, 43.35; H, 3.63; N, 33.70; S, 19.29. Found: C, 43.49; H,
3.34; N, 33.35; S, 19.49.
4.8.24. 1-(5-Methylthiazol-2-yl)-1H-benzotriazole (12am)
Yield: 0.93 g (86%), yellow crystals; mp: 105–106 ꢀC (from
acetone). 1H NMR (CDCl3): d¼2.52 (d, 4J¼1.2 Hz, 3H, CH3), 7.38 (q,
4J¼1.2 Hz, 1H, H-40), 7.47 (t, 3J¼7.2 Hz, 1H, ]CH), 7.63 (t, 3J¼7.2 Hz,
1H, ]CH), 8.10 (d, 3J¼7.2 Hz, 1H, ]CH), 8.43 (d, 3J¼7.2 Hz, 1H,
]CH). 13C NMR (CDCl3): d¼11.96 (q, CH3), 113.36 (d, C-40), 119.99 (d,
C]CH), 125.48 (d, C]CH), 129.48 (d, C]CH), 130.84 (s), 131.24 (s),
137.69 (d, C]CH), 146.37 (s), 159.65 (s). Anal. Calcd for C10H8N4S
(216.27): C, 55.53; H, 3.72; N, 25.90; S, 14.82. Found: C, 55.41; H,
3.71; N, 25.78; S, 15.09.
7. Synthesis of 1d: Austin, P. W. (Imperial Chemical Industries PLC) EP 244962,
1986; Chem. Abstr. 1988, 108, P89483d.
8. Jawabrah Al-Hourani, B. Dissertation, TU Chemnitz: Germany, 2005.
9. For reviews on the synthesis of thiazoles, see: (a) Kikelj, D.; Urleb, U. Science of
Synthesis; Schaumann, E., Ed.; Thieme: Stuttgart, 2002; Vol. 11, pp 627–833; (b)
Liebscher, J. Houben–Weyl, 4th ed.; Schaumann, E., Ed.; Thieme: Stuttgart, 1994;
Vol. E 8b/II, pp 1–398; (c) Dondoni, A.; Merino, P. Comprehensive Heterocyclic
Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon:
Oxford, 1994; Vol. 3, pp 373–474.
10. Gebhardt, W. Ber. Dtsch. Chem. Ges. 1884, 17, 2088–2095.
11. Alternative synthesis of 5: Cornwell, S. P.; Kaye, P. T.; Kent, A. G.; Meakins, G. D.
J. Chem. Soc., Perkin Trans. 1 1981, 2340–2343.
12. Alternative synthesis of 8: Kolosova, M. O. Zh. Obshch. Khim. 1963, 33, 3667–
3671.
13. Alternative synthesis of 9: (a) Forlani, L. Gazz. Chim. Ital. 1981, 111, 159–162; (b)
Erlenmeyer, H.; Herzfeld, L.; Prijs, B. Helv. Chim. Acta 1955, 38, 1291–1294.
14. Synthesis of 11f: Chambers, D.; Denny, W. A.; Buckleton, J. S.; Clark, G. R. J. Org.
Chem. 1985, 50, 4736–4738.
15. Synthesis of 11g: (a) Brunner, H.; Scheck, T. Chem. Ber. 1992, 125, 701–709; (b)
Pleier, A.-K.; Glas, H.; Grosche, M.; Sirsch, P.; Thiel, W. R. Synthesis 2001, 55–62;
(c) Thiel, W. R.; Eppinger, J. Chem.dEur. J. 1997, 3, 696–705.
16. (a) Dehne, H. Houben–Weyl, 4th ed.; Schaumann, E., Ed.; Thieme: Stuttgart,
1994; Vol. E 8d, pp 305–405; (b) Finley, K. T. The Chemistry of Heterocyclic
Compounds, Triazoles: 1,2,3; Montgomery, J. A., Ed.; Wiley: New York, NY, 1980.
17. Jawabrah Al-Hourani, B.; Banert, K.; Walfort, B.; Lang, H. Anal. Sci. 2006, 22,
x275–x276.
4.8.25. 4-(5-Methylthiazol-2-yl)-4H-1,2,4-triazole (12an)
and 1-(5-methylthiazol-2-yl)-1H-1,2,4-triazole (12an0)
Following the general procedure, thiazoles 12an (0.53 g, 64%)
and 12an0 (0.22 g, 26%) were obtained as yellow solids. Each
product was recrystallized from acetone.
Compound 12an. Mp: 105–107 ꢀC. 1H NMR (CDCl3): d¼2.52 (d,
4
4J¼1.2 Hz, 3H, CH3), 7.31 (q, J¼1.2 Hz, 1H, H-40), 8.67 (s, 2H, H-3,
H-5). 13C NMR (CDCl3): d¼12.05 (q, CH3), 132.93 (d, C-40), 138.19 (s,
C-50), 140.20 (d, C-3, C-5), 151.31 (s, C-20). Anal. Calcd for C6H6N4S
(166.21): C, 43.62; H, 3.05; N, 33.91; S, 19.53. Found: C, 43.39; H,
3.42; N, 33.49; S, 19.41.
18. Jawabrah Al-Hourani, B.; Banert, K.; Maichle-Mo¨ssmer, C.; Al-Labadi, A.;
Abu-Rayyan, A. Anal. Sci. 2006, 22, x107–x108.
19. For other examples on the rearrangement of methylenethiazoles to aromatic
isomers, see Ref. 5c and Wipf, P.; Rahman, L. T.; Rector, S. R. J. Org. Chem. 1998,
63, 7132–7133.
Compound 12an0. Mp: 93–94 ꢀC. 1H NMR (CDCl3): d¼2.49 (d,
4J¼1.2 Hz, 3H, CH3), 7.26 (q, 4J¼1.2 Hz, 1H, H-40), 8.04 (s, 1H, ]CH),
8.91 (s, 1H, ]CH). 13C NMR (CDCl3): d¼11.94 (q, CH3), 132.65 (d),
137.62 (d), 140.60 (d), 143.89 (s), 152.63 (s). Anal. Calcd for C6H6N4S
20. Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923–2925.
21. For the technique of flash vacuum pyrolysis, see Ref. 5c,d.