November 2010
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tra were measured on a JEOL JNM-GX400 (400 MHz for 1H and
100.4 MHz for 13C) in deuteriochloroform solutions. Tetramethylsilane was
used as the internal standard and J values were given in Hz. Elemental
analyses were performed on a Perkin-Elmer 2400 elemental analyzer.
Preparation of 2-Acyl-3-amino-4-(1-pyridinio)thiophene-5-thiolates
4a—o The preparation of compounds 4a—o was carried out by modifying
Tominaga’s procedure.15) Typical procedure: A solution of 1-(cyanomethyl)
pyridinium chloride (1, 0.10 mol), and carbon disulfide (11.4 g, 0.15 mol) in
ethanol (50 ml) was treated with aqueous sodium hydroxide (10 g, 0.25 mol
in 15 ml of water) under stirring in an ice bath for 20 min, and then an alkyl-
ating agent (2, 0.1 mol) was added to the reaction mixture. The resulting
solution was allowed to react at room temperature for a further 4 h. The solu-
tion was then poured into ice water (300 ml) and the precipitates which sepa-
rated were collected by suction and then dried. The products thus obtained
were only pyridinium ylides 3e, j, o or the expected 2-acyl-3-amino-4-(1-
pyridinio)thiophene-5-thiolates (4a—d, f—i, k—n) involving various
amounts of 3a—d, f—i, k—n. These mixtures of 3 or/and 4 were heated
without any solvent at 60—80 °C at a reduced pressure (3 Torr) until the
generation of water completely ceased (ca. 2—7 d). These compounds 4a—o
were purified by the recrystallization from acetone. On the other hand, a
similar reaction of 1-cyanomethyl-4-methylpyridinium chloride (1d) and
phenacyl bromide (2a) provided only intractable polymeric substances and
the structural analysis was unsuccessful because of its low solubility.
The physical and spectral data of known compounds 3f, j and 4f, j were in
accord with those described earlier by us19) and Tominaga et al.15) and some
data for the new compounds which were isolated are shown below.
3-Methylpyridinium 1-(1-Cyano-2-ethoxycarbonylmethylthio-2-thioxo)
ethylide (3o): 59%; yellow needdles (from CHCl3–Et2O); mp 94—96 °C. IR
(KBr) cmϪ1: 1723, 2151. 1H-NMR (CDCl3) d: 1.25 (3H, t, Jϭ7.1 Hz,
OCH2CH3), 2.59 (6H, s, 3,5-diMe), 3.75 (2H, s, CH2), 4.15 (2H, q, Jϭ
7.1 Hz, OCH2CH3), 7.43 (2H, m, Ph-H), 7.51 (1H, m, Ph-H), 7.83 (2H, m,
Ph-H), 8.04 (1H, br s, 4-H), 8.47 (2H, br s, 2,6-H). Anal. Calcd for
C13H14N2O2S2: C, 53.04; H, 4.79; N, 9.52%. Found: C, 53.10; H, 4.93; N,
9.75%.
Fig. 4. ORTEP Drawing of Compound 8e
3-Amino-2-benzoyl-4-(3,5-dimethyl-1-pyridinio)thiophene-5-thiolate
(4a): 83%; red prisms; mp 292—294 °C. IR (KBr) cmϪ1: 1582, 3250, 3358.
1H-NMR (CDCl3) d: 2.61 (6H, s, 3,5-diMe), 6.31 (br, NH), 7.35—7.67 (3H,
m, Ph-H), 7.79 (2H, br d, Jϭ6.2 Hz, Ph-H), 8.01 (1H, s, 4-H), 8.49 (2H, s,
2,6-H). Anal. Calcd for C18H16N2OS2: C, 63.50; H, 4.74; N, 8.23%. Found:
C, 63.30; H, 4.72; N, 8.45%.
3-Amino-2-(4-chlorobenzoyl)-4-(3,5-dimethyl-1-pyridinio)thiophene-5-
thiolate (4b)20): 80%; red prisms; mp Ͼ300 °C. IR (KBr) cmϪ1: 1576, 3258,
3372. Anal. Calcd for C18H15ClN2OS2: C, 57.67; H, 4.03; N, 7.47%. Found:
C, 57.60; H, 4.05; N, 7.52%.
3-Amino-2-(4-bromobenzoyl-4-(3,5-dimethyl-1-pyridinio)thiophene-5-
thiolate (4c)20): 73%; red prisms; mp 296—298 °C. IR (KBr) cmϪ1: 1574,
3254, 3364. Anal. Calcd for C18H15BrN2OS2: C, 51.55; H, 3.61; N, 6.68%.
Found: C, 51.55; H, 3.60; N, 6.67%.
2-Acetyl-3-amino-4-(3,5-dimethylpyridinio)thiophene-5-thiolate (4d): 59%;
red prisms; mp Ͼ300 °C. IR (KBr) cmϪ1: 1574, 3248, 3376. 1H-NMR
(CDCl3) d: 2.25 (3H, s, Ac), 2.60 (6H, s, 3.5-diMe), 5.90 (br, NH), 7.99
(1H, s, 4-H), 8.48 (2H, s, 2,6-H). Anal. Calcd for C13H14N2OS2: C, 56.09; H,
5.07; N, 10.06%. Found: C, 56.42; H, 4.95; N, 9.85%.
Fig. 5. Possible Routes for the Cyclization Starting from Pyridinium Salts
sistent with the proposed composition. From its elemental
analysis and positive Beilstein test we suspected that this
compound 13e may be a condensation product between the
pyridinium salt 6e and the solvent (CHCl3). The X-ray analy-
sis (see Fig. 4) confirmed that compound 13e is 1-[3-amino-
2-ethoxycarbonyl-5-(methylthio)thiophen-4-yl]-3,5-di-
methyl-4-trichloromethyl-1,4-dihydropyridine.
Mechanistically, the formation of thieno[3Ј,4Ј:4,5]imi-
dazo[1,2-a]pyridine derivatives 7, 10, and 12 can be also
considered by an alternative route (path b in Fig. 5) other
than the 1,5-dipolar cyclization one (path a) described earlier
in Fig. 1. That is, the intramolecular nucleophilic attack of
the 3-amino group onto the 2-position of the pyridinium ring
of 1-[2-acyl-5-alkylthio-3-aminothiophen-4-yl]pyridinium
salts such as D, followed by the elimination of each one mol-
ecule of HX and hydrogen from the cycloadducts (F) should
give the same products 7, 10, and 12. However, the possibil-
ity of the path b is not so high, because we could not detect
3-Amino-4-(3,5-dimethyl-1-pyridinio)-2-(ethoxycarbonyl)thiophene-5-
thiolate (4e): 83%; red prisms; mp 284—286 °C. IR (KBr) cmϪ1: 1653,
1
3233, 3397. H-NMR (CDCl3) d: 1.33 (3H, t, Jϭ7.1 Hz, OCH2CH3), 2.59
(6H, s, 3,5-diMe), 4.25 (2H, q, Jϭ7.1 Hz, OCH2CH3), 5.12 (br, NH), 7.95
(1H, s, 4-H), 8.52 (2H, s, 2,6-H). Anal. Calcd for C14H16N2O2S2: C, 54.52;
H, 5.23; N, 9.08%. Found: C, 54.62; H, 5.40; N, 8.82%.
3-Amino-2-(4-chlorobenzoyl)-4-(1-pyridinio)thiophene-5-thiolate (4g)20)
:
1
the presence of any cycloadduct (F) in the H-NMR spsctra
89%; red prisms; mp 294—296 °C. IR (KBr) cmϪ1: 1543, 3229, 3348. Anal.
Calcd for C16H11ClN2OS2: C, 55.41; H, 3.20; N, 8.08%. Found: C, 55.69; H,
3.10; N, 7.86%.
of some pyidinium salts. Perhaps, the higher acidity of the
aromatic amines in the pyridinium salts D than that of
aliphatic amines may be the driving force of these reactions.
In conclusion, we could develop a new and practical
preparative method for 1-acyl-3-(substituted methylthio)
thieno[3Ј,4Ј:4,5]imidazo[1,2-a]pyridine derivatives, though
their yields were not so high.
3-Amino-2-(4-bromobenzoyl)-4-(1-pyridinio)thiophene-5-thiolate (4h)20)
:
79%; red prisms; mp 300 °C. IR (KBr) cmϪ1: 1576, 3239, 3345. Anal. Calcd
for C16H11BrN2OS2: C, 49.11; H, 2.83; N, 7.16%. Found: C, 49.27; H, 2.99;
N, 6.87%.
2-Acetyl-3-amino-4-(1-pyridinio)thiophene-5-thiolate (4i)20): 88%; red
prisms; mp Ͼ300 °C. IR (KBr) cmϪ1: 1572, 3244, 3337. Anal. Calcd for
C11H10N2OS2: C, 52.78; H, 4.03; N, 11.19%. Found: C, 52.86; H, 4.25; N,
10.88%.
Experimental
Melting points were measured on a Yamagimoto micro melting point ap-
3-Amino-2-benzoyl-4-(3-methyl-1-pyridinio)thiophene-5-thiolate (4k)20)
:
paratus and were not corrected. IR spectra were measured on a JASCO 88%; red prisms; mp 289—291 °C. IR (KBr) cmϪ1: 1582, 3252, 3360. Anal.
FT/IR-5300 IR spectrophotometer from samples as KBr pellets. NMR spec-
Calcd for C17H14N2OS2: C, 62.55; H, 4.32; N, 8.58%. Found: C, 62.68; H,