Preparation of 3,4-di-t-butylthiophene 1-imide and its N-substituted derivatives

Article abstract of DOI:10.1016/S0040-4039(00)01481-7

Treatment of 3,4-di-t-butylthiophene 1-oxide with (CF₃CO)₂O or (CF₃SO₂)₂O, followed by reaction with RSO₂NH₂, ROC(=O)NH₂, or RCONH₂ furnished a series of 1-

Full text of DOI:10.1016/S0040-4039(00)01481-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8461–8465
Preparation of 3,4-di-t-butylthiophene 1-imide and its
N-substituted derivatives
Takashi Otani, Yoshiaki Sugihara, Akihiko Ishii and Juzo Nakayama*
Department of Chemistry, Faculty of Science, Saitama University, Urawa, Saitama 338-8570, Japan
Received 3 August 2000; revised 25 August 2000; accepted 1 September 2000
Abstract
Treatment of 3,4-di-t-butylthiophene 1-oxide with (CF3CO)2O or (CF3SO2)2O, followed by reaction
with RSO2NH2, ROC(ꢀO)NH2, or RCONH2 furnished a series of 1-imino derivatives of 3,4-di-t-butyl-
thiophene, which carry an electron-withdrawing substituent on the imino nitrogen atom. Treatment of an
t
imino derivative (substituent on the nitrogen atom=CO2 Bu) with CF3CO2H gave the corresponding
aminosulfonium salt, whose deprotonation led to the N-unsubstituted parent 1-imide derivative. © 2000
Elsevier Science Ltd. All rights reserved.
Keywords: thiophenes; sulfimides/sulfilimines; sulfonium salts.
The chemistry of sulfilimines has been investigated from a variety of standpoints such as
development of new syntheses, structures, reactivities, and applications to organic synthesis.1 As
for sulfilimine derivatives of monocyclic thiophenes, only a few derivatives have been synthe-
sized to date.2–4 The sulfilimines of this class would be of much importance as cyclic dienes.
Their chemistry is also of interest in comparison with that of thiophene 1-oxides, which have
attracted much attention recently.5 We have previously shown that treatment of 3,4-di-t-butyl-
thiophene (1) with TsNꢀIPh in the presence of a Cu(I) catalyst furnishes the 1-imino derivative
(2a), 1,1-diimino derivative (3), and some other compounds.3 However, we were frustrated at the
following three drawbacks of the method: (1) the isolation procedure of 2a is laborious because
of the formation of many products; (2) the reaction required the use of twenty molar amounts
of 1 to obtain 2a in 61% yield, and (3) by conventional detosylation methods, 2a was not
converted to the N-unsubstitued parent compound (6), which is isolectronic with the corre-
sponding thiophene 1-oxide and whose reactivities are expected to largely differ from those of
the N-substituted compounds. These prompted us to develop an alternative synthesis of 2a and
related compounds by using 3,4-di-t-butylthiophene 1-oxide (4) as the starting material, which
was easily prepared in good yield by oxidation of the thiophene 1 with m-chloroperbenzoic acid
in the presence of BF3·Et2O and is kinetically stabilized by steric protection.6,7
* Corresponding author. Tel: +81-48-858-3390; fax: +81-48-858-3700; e-mail: nakaj@post.saitama-u.ac.jp
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01481-7

8462
The 1-oxide 4 (1 mmol) was treated with two molar amounts of (CF3CO)2O (TFAA) at
−78°C. p-Toluenesulfonamide (2 mmol) was added to this mixture at the same temperature. The
resulting mixture was warmed slowly to room temperature, and the reaction was quenched by
addition of aqueous Na2CO3. The mixture was worked up in the usual manner and purified by
silica-gel column chromatography to give 2a in 86% yield (Table 1, run 1).8 The reaction, in
which (CF3SO2)2O (Tf2O) was used instead of TFAA under similar conditions, also afforded 2a
in 79% yield (run 2). Under these conditions, a series of derivatives 2a–f were synthesized in
satisfactory yields, as shown in Table 1.8
Table 1
Preparation of N-substituted 1-imino derivatives 2 of 3,4-t-butylthiophene
Run
1-Imino derivative
R
Acid anhydride
Yield (%)
1
2
3
4
5
6
7
2a
2a
2b
2c
2d
2e
2f
SO2C6H4CH3(p)
SO2C6H4CH3(p)
SO2C6H5
TFAA
Tf2O
Tf2O
TFAA
TFAA
TFAA
TFAA
86
79
74
90
82
53
74
CO2Et
t
CO2 Bu
COCH3
COC6H4CH3
Although the above synthesis was quite satisfactory in many cases, unsatisfactory but
interesting exceptions were found. Treatment of 4 with TFAA and then with H2NCN yielded
the trifluoroacetyl derivative (2g) in 85% yield, but not the expected cyano derivative (2h).8
Similarly, treatment of 4 with TFAA and then with H2NCONH2 also gave 2g in 83% yield.
Neither of the expected 2i or 2j was formed. An analogy of the present reaction is found in the
reaction of DMSO with TFAA and then with H2NCONH2 in CH2Cl2, which gave
Me2SꢀNCOCF3 in 80% yield.9 The reaction of 4 with MeNH2, after treatment with TFAA, also
failed to give the expected derivative (2k) with quantitative recovery of 4.

8463
In order to obtain the N-unsubstituted parent compound (6), 2d was treated with CF3CO2H.10
The reaction satisfactorily yielded the aminosulfonium salt (5) quantitatively, which is the first
aminosulfonium salt of thiophenes.11 Treatment of a suspension of 5 in ether with aqueous
NaOH gave the expected 1-imide 6 and the thiophene 1 in the ratio 97:3 quantitatively, whereas
treatment of 5 with NaH in ether gave 6 and 1 in the ratio 58:42.12 The formation of 1, in
addition to 6, indicates that nucleophiles attack not only the amino hydrogen atom but also the
amino nitrogen atom (7); in other words, 5 possesses potential to serve as an amination reagent.
Compound 6 provides the first example of N-unsubstituted 1-imino derivatives of thiophenes.
The 1-imide 6 is storable at below −20°C at least for one month without any appreciable
decomposition, but it decomposed to thiophene 1 quantitatively through an unknown mecha-
nism when its CDCl3 solution was heated at 50°C for 6 h. It was converted into 2a
quantitatively by treatment with TsCl, thus suggesting that a variety of N-substituted com-
pounds would be derived from 6, if necessary.
The most characteristic features of the structure of 2 are found in their IR spectra.13 The
carbonyl stretching vibrations appear in abnormally low frequency ranges (Table 2). In
particular, the carbonyl stretching vibration of 2f appears at a frequency as low as 1541 cm−1.
This indicates that the 1,3-dipolar canonical structure 8 is the most suitable expression of the
structure of these compounds.
1
Fig. 1 summarizes the chemical shift values (l) in the H and 13C NMR spectra of 1 and its
S-heteroatom-substituted derivatives 4, 6, 9, and 10.14 The higher chemical shift value of the
a-hydrogen atoms of 6 (l 6.81), compared with that of 1 (l 7.16), would be indicative of the loss
of the aromaticity (ring current effect) of the thiophene ring of 6, as was true of the 1-oxide 4.7
Interestingly, the a-hydrogen atoms of 4 and 6 resonate at lower fields than those of 9 and 10,
where two electronegative heteroatoms are bound to the sulfur atom. Finally, it would be
worthy of mention that the a-carbon atom peaks of 4 and 6 appeared at lower fields than the
corresponding peaks of 9 and 10 in the 13C NMR spectra.
Table 2
Carbonyl stretching vibrations of 2c–g in the IR spectra
Compounds
wCꢀO (cm−1
2c
2d
2e
2f
2g
)
1636
1639
1573
1541
1627

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1
Figure 1. H and 13C NMR spectra of 1 and its 1-heteroatom-substituted derivatives (chemical shift was expressed in
l values)
Acknowledgements
T.O. thanks the Japanese Society for the Promotion of Science for Young Scientists for a
Research Fellowship.
References
1. Taylor, P. C. Sulfur Reports 1999, 21, 241 and references cited therein.
2. (a) Meth-Cohn, O.; van Vuuren, G. J. Chem. Soc., Chem. Commun. 1984, 190. (b) Meth-Cohn, O.; van Vuuren,
G. J. Chem. Soc., Perkin Trans. 1 1986, 233. (c) Meth-Cohn, O.; van Vuuren, G. J. Chem. Soc., Perkin Trans.
1 1986, 245. (d) Dillen, J. L. M.; Meth-Cohn, O.; van Vuuren, G. J. Chem. Soc., Perkin Trans. 1 1987, 2659.
3. (a) Otani, T.; Sugihara, Y.; Ishii, A.; Nakayama, J. Tetrahedron Lett. 1999, 40, 3785. (b) Otani, T.; Sugihara, Y.;
Ishii, A.; Nakayama, J. Chem. Lett. 2000, 744.
4. For the synthesis and reactivities of dibenzo derivatives, see (a) Svoronos, P.; Horak, V. Synthesis 1979, 596. (b)
Morita, H.; Tatami, A.; Kim, B. J.; Yoshida, M.; Tsubota, K.; Yoshimura, T.; Fujii, T.; Ono, S. 30th Congress
of Heterocyclic Chemistry, Abstract Book, p. 82, November, 1999, Hachioji, Japan. (c) Tatami, A.; Kim, B. J.;
Tsubota, K.; Yoshimura, T.; Fujii, T.; Ono, S.; Morita, H. 78th Annual Meeting of the Chemical Society of
Japan, Abstract Book, 3G311, March, 2000, Funabashi, Japan.
5. For reviews, see: (a) Nakayama, J.; Sugihara, Y. Sulfur Reports 1997, 19, 349. (b) Nakayama, J. Sulfur Reports
2000, 22, 123.
6. Furukawa, N.; Zhang, S.; Sato, S.; Higaki, M. Heterocycles 1997, 44, 61.
7. Nakayama, J.; Yu, T.; Sugihara, Y.; Ishii, A. Chem. Lett. 1997, 499.
1
8. Compound 2b: mp 133–135°C; H NMR (400 MHz, CDCl3) l=1.37 (s, 18H), 6.70 (s, 2H), 7.43–7.53 (m, 3H),
7.88–7.90 (m, 2H); 13C NMR (100.6 MHz, CDCl3) l=31.8, 36.5, 126.9, 128.3, 128.6, 131.6, 143.2, 162.0.
Compound 2c: viscous oil; 1H NMR (400 MHz, CDCl3) l=1.27 (t, J=7.1 Hz, 3H), 1.42 (s, 18H), 4.13 (q, J=7.1
Hz, 2H), 6.92 (s, 2H); 13C NMR (100.6 MHz, CDCl3) l=14.7, 32.0, 36.5, 62.1, 128.5, 162.4, 166.0. Compound
1
2d: mp 129–131°C; H NMR (400 MHz, CDCl3) l=1.42 (s, 18H), 1.49 (s, 9H), 6.92 (s, 2H); 13C NMR (100.6
1
MHz, CDCl3) l=28.4, 32.0, 36.4, 79.4, 128.8, 162.2, 165.6. Compound 2e: mp 90–91°C; H NMR (400 MHz,
CDCl3) l=1.44 (s, 18H), 2.14 (s, 3H), 7.10 (s, 2H); 13C NMR (100.6 MHz, CDCl3) l=23.4, 31.9, 36.5, 126.9,
1
162.7, 182.1. Compound 2f: mp 110–111°C; H NMR (400 MHz, CDCl3) l=1.46 (s, 18H), 2.37 (s, 3H), 7.16 (d,
J=8.0 Hz, 2H), 7.22 (s, 2H), 7.97 (d, J=8.0 Hz, 2H); 13C NMR (100.6 MHz, CDCl3) l=21.5, 32.1, 36.6, 127.4,
1
128.6, 128.8, 132.8, 141.0, 162.4, 177.4. Compound 2g: mp 158–160°C; H NMR (400 MHz, CDCl3) l=1.46 (s,
18H), 7.15 (s, 2H); 13C NMR (100.6 MHz, CDCl3) l=31.8, 36.9, 117.0 (q, 1J(C,F)=286 Hz), 125.2 (dt,
2
5J(C,F)=19, 86 Hz), 164.7, 167.3 (q, J(C,F)=35 Hz).
9. Sharma, A. K.; Ku, T.; Dawson, A. D.; Swern, D. J. Org. Chem. 1975, 40, 2758.
10. Bach, T.; Ko¨rber, C. Eur. J. Org. Chem. 1999, 1033.
1
11. Compound 5: mp 89–94°C (decomp.); H NMR (400 MHz, CDCl3) l=1.44 (s, 18H), 6.97 (s, 2H), 7.16 (broad
1
2
s, 2H); 13C NMR (100.6 MHz, CDCl3) l=31.7, 37.0, 116.7 (q, J(C,F)=294 Hz), 126.5, 161.8 (q, J(C,F)=34
Hz), 165.7.

8465
1
12. Compound 6: viscous oil (solidifies in a refrigerator); H NMR (400 MHz, CDCl3) l=1.44 (s, 18H), 2.34 (broad
s, 1H), 6.81 (s, 2H); 13C NMR (100.6 MHz, CDCl3) l=32.1, 35.9, 135.1, 158.4.
13. The SꢀN stretching vibrations of 2c–g were not assigned in an unambiguous manner. Ab initio MO calculations
of the 1-acetylimino derivative of the parent thiophene (C4H4SꢀNCOMe) at the B3LYP/6-31G* level predicted
that the CꢀO stretching vibration appears at 1592 cm−1 as an intense band, while the SꢀN stretching vibration
at 586 cm−1 appears as a weak band (scaling factor, 0.96). We thank Dr. A. Sakamoto of our department for the
calculations.
14. (a) Nakayama, J.; Hasemi, R.; Yoshimura, K.; Sugihara, Y.; Yamaoka, S. J. Org. Chem. 1998, 63, 4912. (b)
Nakayama, J.; Sano, Y.; Sugihara, Y.; Ishii, A. Tetrahedron Lett. 1999, 40, 3785.
.