Opening of the furan ring in 2-R-amino- 3-furfurylthiophenes by the action of acids

Article abstract of DOI:10.1007/s10593-011-0715-2

A new method is proposed for the production of derivatives of thieno[2,3-b]pyrrole on the basis of acid-catalyzed recyclization of the furan ring in 2-R-amino-3-furfurylthiophenes. It was established that the direction of the transformations occurring under the influence of a mixture of hydrochloric and acetic acids and also the structure of the obtained compounds depend on the nature of the protecting group.

Full text of DOI:10.1007/s10593-011-0715-2

Chemistry of Heterocyclic Compounds, Vol. 47, No. 1, April, 2011 (Russian Original Vol. 47, No. 1, January, 2011)
OPENING OF THE FURAN RING IN 2-R-AMINO-
3-FURFURYLTHIOPHENES BY THE ACTION OF ACIDS
T. A. Stroganova1*, V. K. Vasilin1, and E. A. Elizarova1
A new method is proposed for the production of derivatives of thieno[2,3-b]pyrrole on the basis of acid-
catalyzed recyclization of the furan ring in 2-R-amino-3-furfurylthiophenes. It was established that the
direction of the transformations occurring under the influence of a mixture of hydrochloric and acetic
acids and also the structure of the obtained compounds depend on the nature of the protecting group.
Keywords: 2-amino-3-benzoylthiophenes, 2-R-amino-3-furfurylthiophenes, thieno[2,3-b]pyrrole, furan ring,
opening, recyclization.
In the present work while continuing our investigations into the use of 2-aminothiophene derivatives in
synthesis [1] we chose 2-amino-3-benzoylthiophene as subject of investigation. The interest in this compound is
explained by the fact that it can be regarded as a hetero analog of ortho-aminobenzophenones, which are used as
starting compounds in the synthesis of derivatives of indole during the recyclization of benzylfurans [2-4]. By
replacing the aromatic ketones by the heterocyclic analog it is possible to obtain derivatives of the condensed
heterocyclic system thieno[2,3-b]pyrrole. For this purpose we synthesized furylmethane structures based on
2-amino-3-benzoylthiophenes 1a,b and studied their transformations in an acidic medium.
O
O
Ph
HO
Ph
NH2
Ph
Ph
Me
O
R
iii
ii
i
H
N
H
H
N
(CH2)n
(CH2)n
(CH2)n
N
(CH2)n
S
S
R
S
S
R
1a,b
3a–f
2a–f
4a–f
i: TsCl or RCOCl, pyridine, toluene, boiling; ii: NaBH4, EtOH+THF; iii: 2-methylfuran, CH2Cl2, CF3COOH.
1a, 24 ad n = 4; 1b, 24 e,f n = 3; 24 a,e R = Ts, b,f R = MeCO, c R = PhCO, d R = thenoyl
The thienylfurylmethanes 2 were obtained as a result of a sequence of reactions, including acylation of
the amino group of the amino ketones 1a,b, reduction of the carbonyl function, and alkylation of the 2-methyl-
furan by the obtained alcohols 4a-f.
_______
* To whom correspondence should be addressed, e-mail: stroganova@kubstu.ru, tatka_s@mail.ru.
1 Kuban State University of Technology, Department of Organic Chemistry, Moskovskaja 2, Krasnodar 350072,
Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 33-41, January, 2011. Original
article submitted August 16, 2010.
22
0009-3122/11/4701-0022©2011 Springer Science+Business Media, Inc.

Recyclization of the furan ring in the methanes 2a-f was realized by heating in a mixture of hydrochloric
and glacial acetic acids.
As for the aromatic analogs [2, 3], we used the N-tosyl-substituted methanes 2a,e for the synthesis of the
pyrrole derivative. The reaction of compounds 2a,e with the mixture of acids leads to opening of the furan ring
accompanied by secondary cyclization, resulting in the formation of derivatives of thieno[2,3-b]pyrrole 5a,b.
TABLE 1. The Physicochemical and Spectral Characteristics of Compounds 2-7
Found, %
——————
Calculated, %
Com-
pound*
Empirical
formula
Yield,
%
mp, °C
C
H
N
C27H27NO3S2
C22H23NO2S
C27H25NO2S
C25H23NO2S2
C26H25NO3S2
C21H21NO2S
C22H21NO3S2
C17H17NO2S
C22H19NO2S
C20H17NO2S2
C21H19NO3S2
C16H15NO2S
C22H23NO3S2
C17H19NO2S
C22H21NO2S
C20H19NO2S2
C21H21NO3S2
C16H17NO2S
C27H27NO3S2
C26H25NO3S2
C22H23NO2S
C21H21NO2S
C27H27NO3S
C25H25NO3S2
C15H15NOS
67.87
67.90
72.31
72.30
75.88
75.85
69.22
69.25
67.41
67.36
71.79
71.77
64.23
64.21
68.23
68.20
73.08
73.10
65.40
65.37
63.49
63.45
67.30
67.34
5.72
5.70
6.37
6.34
5.86
5.89
5.37
5.35
5.50
5.44
5.96
6.02
5.12
5.14
5.69
5.72
5.34
5.30
4.68
4.66
4.83
4.82
5.36
5.30
2.95
2.93
3.86
3.83
3.30
3.28
3.20
3.23
2.99
3.02
4.03
3.99
3.41
3.40
4.72
4.68
3.86
3.87
3.78
3.81
3.47
3.52
4.84
4.91
181-183
62
63
79
70
68
65
83
87
91
90
85
87
88
89
76
94
91
88
69
72
55
58
47
64
21
2a
2b
2c
2d
2e
2f
145-146
Light-yellow oil
125-126
175-176
133-134
140-142
123-124
161-163
158-160
184-186
128-130
Yellow oil
162-163
> 150 (dec.)
205-206
> 135 (dec.)
190-191
189-191
185-187
138-139
119-121
Yellow oil
140-142
155-156
3a
3b
3c
3d
3e
3f
63.90
5.61
3.39
4a
4b
4c
4d
4e
4f
67.71
67.74
72.72
72.70
65.05
65.01
63.13
6.32
6.35
5.85
5.82
5.17
5.18
5.30
4.63
4.65
3.88
3.85
3.82
3.79
3.51
66.79
66.87
67.92
67.90
67.43
67.36
72.33
72.30
71.82
71.77
72.81
72.78
66.52
66.49
70.04
70.01
5.91
5.96
5.73
5.70
5.40
5.44
6.36
6.34
5.95
6.02
6.14
6.11
5.59
5.58
5.81
5.87
4.90
4.87
2.90
2.93
3.07
3.02
3.80
3.83
4.04
3.99
3.11
3.14
3.13
3.10
5.47
5.44
5a
5b
5c
5d
6a
6b
7
_______
* For compounds 4a,e only the calculated data are given.
23

O
O
Ph
Ph
Me
HCl/AcOH
H
Me
N
(CH2)n
2a,e
(CH2)n
N
Ts
O
S
S
Ts
5a,b
5 a n = 4, b n = 3
If the methanes 2b,f with an acetyl protecting group are treated it is possible to expect the formation of
two substances N-acetylthienopyrrole and NH-thienopyrrole, i.e., the products from recyclization of the furan
ring with retention or with removal of the protecting group. Earlier we described the second type of
recyclization for methane structures of the thieno[2,3-b]pyridine series [5].
During the reaction of compounds 2b,f with the mixture of acids it was found that the N-acetyl-
substituted thieno[2,3-b]pyrroles 5c,d were formed as the main products, i.e., in this case opening of the furan
ring and subsequent closure of the pyrrole ring took place without elimination of the protecting group.
Me
Me
Me
O
O
Ph
Ph
HCl/AcOH
2b,f
N
(CH2)n
NH
(CH2)n
S
S
O
5c,d
5 c n = 4, d n = 3
In contrast to the cases examined above, only opening of the furan ring, leading to the formation of the
corresponding 1,4-diketones 6a,b, occurs in the reaction of the N-benzoyl- and N-thenoyl derivatives 2c and 2d
with the HClAcOH system.
O
Me
Ph
O
HCl/AcOH
H
H
N
+
N
2c,d
S
S
O
O
R
Ph
6a,b
7
6 a R = Ph; b R = 2-thienyl
A similar transformation was observed during the acid-catalyzed recyclization of furylmethane
structures containing a 2-benzoylaminothieno[2,3-b]pyridine fragment [5].
In the case of the thiophenes 2c,d it should be noted that the opening of the furan ring is accompanied
by an extremely unusual transformation; thus, when compound 2c was treated the 2-benzoylaminothiophene 7
unsubstituted at position 3 was isolated from the reaction mixture by column chromatography in addition to the
diketone 6a. It is probably formed as a result of protonation at position 3 of the thiophene ring, leading to
elimination of the stable phenylfurylmethyl cation, which is a good leaving group. For compound 2d the
formation of the similar compound was only observed by TLC, and it could not be isolated.
24

TABLE 2. The 1H NMR Spectra of Compounds 2-7
Com-
Chemical shifts, δ, ppm (J, Hz)
pound
1
2
2a
1.37-1.67 (4Н, m, 2СН2); 2.07-2.20 (2Н, m, СН2); 2.23 (3Н, s, СН3); 2.37 (3Н, s, СН3);
2.50-2.56 (2Н, m, СН2); 5.61 (1Н, d, J = 2.9, H furyl); 5.65 (1Н, s, СН);
5.97 (1Н, d, J = 2.9, H furyl); 6.89 (2Н, d, J = 7.3, H phenyl);
7.19-7.35 (5Н, m, H phenyl); 7.65 (2Н, d, J = 8.1, H phenyl); 9.99 (1Н, br. s, NH)
2b
2c
2d
2e
1.46-1.69 (4Н, m, 2СН2); 1.79-1.90 (1Н, m, СН2); 1.96 (3Н, s, СН3СО);
2.01-2.13 (1Н, m, СН2); 2.24 (3Н, s, СН3); 2.54-2.63 (2Н, m, СН2); 5.69 (1Н, s, СН);
5.74 (1Н, d, J = 2.9, H furyl); 5.98 (1Н, d, J = 2.9, H furyl); 7.11 (2Н, d, J = 7.3, H phenyl);
7.17-7.35 (3Н, m, H phenyl); 9.58 (1Н, br. s, NH)
1.18-1.31 (2Н, m, СН2); 1.52-1.76 (2Н, m, СН2); 2.11-2.27 (5Н, m, СН3 + СН2);
2.60-2.68 (2Н, m, СН2); 5.65 (1Н, s, СН); 5.71 (1Н, d, J = 2.9, H furyl);
5.94 (1Н, d, J = 2.9, H furyl); 7.16-7.33 (5Н, m, H phenyl); 7.42-7.51 (3Н, m, H phenyl);
7.70 (2Н, d, J = 8.1, H phenyl); 9.58 (1Н, br. s, NH)
1.51-1.76 (4Н, m, 2СН2); 1.95-2.17 (2Н, m, СН2); 2.19 (3H, s, CH3);
2.59-2.70 (2Н, m, СН2); 5.60 (1Н, s, СН); 5.76 (1Н, d, J = 2.9, H furyl);
5.92 (1Н, d, J = 2.9, H furyl); 7.12-7.34 (6Н, m, H phenyl + H-4 thienyl);
7.70 (1Н, d, J = 2.9, H-5 thienyl); 7.82 (1Н, d, J = 5.1, H-3 thienyl); 9.63 (1Н, br. s, NH)
1.96-2.01 (2Н, m, СН2); 2.16 (3Н, s, СН3); 2.37 (3Н, s, СН3);
2.32-2.49 (5Н, m, СН2 + СН3); 5.50 (1Н, d, J = 2.9, H furyl); 5.63 (1Н, s, СН);
5.81 (1Н, d, J = 2.9, H furyl); 7.19-7.26 (3Н, m, H phenyl); 7.28 (2Н, d, J = 8.1, H phenyl);
7.51-7.54 (2H, m, Н phenyl); 7.71 (2Н, d, J = 8.1, H phenyl); 9.59 (1Н, br. s, NH)
2f
2.01 (3Н, s, СН3); 2.05-2.26 (7Н, m, 2СН2 + СН3); 2.64-2.74 (2Н, m, СН2);
5.64 (1Н, s, СН); 5.72 (1Н, d, J = 3.0, Н furyl); 5.97 (1Н, d, J = 3.0, Н furyl);
7.03-7.11 (2Н, m, Н phenyl); 7.13-7.33 (3Н, m, Н phenyl); 9.88 (1Н, br. s, NH)
3a
3b
1.53-1.64 (2Н, m, СН2); 1.65-1.77 (2Н, m, СН2); 2.11-2.22 (2Н, m, СН2);
2.32 (3Н, s, СН3); 2.55-2.69 (2Н, m, СН2); 7.28 (2Н, d, J = 8.1, H phenyl);
7.41-7.65 (7H, m, H phenyl); 10.18 (1Н, br. s, NH)
1.51-1.59 (2Н, m, СН2); 1.68-1.76 (2Н, m, СН2); 1.98 (3H, s, CH3);
2.02-2.09 (2Н, m, СН2); 2.60-2.67 (2Н, m, СН2); 7.49-7.54 (2Н, m, H phenyl);
7.59-7.67 (3Н, m, H phenyl); 10.65 (1Н, br. s, NH)
3c
1.47-1.88 (4Н, m, 2СН2); 2.09-2.25 (2Н, m, СН2); 2.62-2.78 (2Н, m, СН2);
7.42-7.74 (10Н, m, H phenyl); 11.45 (1Н, br. s, NH)
3d
1.56-1.88 (2H, m, CH2); 2.40-2.58 (2H, m, CH2); 2.61-2.79 (2H, m, CH2);
7.18 (1H, dd, J = 3.0, J = 4.9, H-4 thienyl); 7.44 (2H, d, J = 7.8, H-2,6 phenyl);
7.55-7.67 (4H, m, Н phenyl + H-5 thienyl); 7.76 (1H, d, J = 4.9, H-3 thienyl);
10.88 (1H, br. s, NH)
3e
2.16-2.23 (2Н, s, СН2); 2.29 (3Н, s, СН3); 2.34-2.38 (2Н, s, СН2); 2.76-2.80 (2Н, s, СН2);
7.27 (2Н, d, J = 8.1, H phenyl); 7.45-7.55 (5Н, m, Н phenyl);
7.59-7.64 (2Н, m, Н phenyl); 10.41 (1Н, br. s, NH)
3f
2.08-2.16 (2Н, m, СН2); 2.18 (3Н, s, СН3); 2.43-2.54 (2Н, m, СН2);
2.72-2.81 (2Н, m, СН2); 7.46-7.62 (5Н, m, H phenyl); 11.28 (1Н, br. s, NH)
4b
1.42-1.70 (4Н, m, 2СН2); 1.89-2.03 (1Н, m, СН2); 2.07 (3H, s, CH3);
2.25-2.40 (1Н, m, СН2); 2.51-2.60 (2Н, m, СН2); 5.93 (1H, d, J = 3.7, CH-OH);
5.97 (1H, d, J = 3.7, CH-OH); 7.14-7.37 (5Н, m, H phenyl); 10.17 (1Н, br. s, NH)
4c
1.55-1.87 (4Н, m, 2СН2); 2.02-2.49 (2Н, m, СН2); 2.53-2.70 (2Н, m, СН2);
5.91 (1Н, d, J = 3.7, СН-OH); 6.69 (1Н, d, J = 3.7, CH-ОН); 7.20-7.39 (5Н, m, H phenyl);
7.50-7.76 (3Н, m, H phenyl); 7.85 (2Н, d, J = 8.1, H phenyl); 11.19 (1Н, s, NH)
4d
1.52-1.78 (4H, m, 2CH2); 2.08-2.19 (1H, m, CH2); 2.23-2.33 (1H, m, CH2);
2.55-2.65 (2H, m, CH2); 5.85 (1H, br. s, CH-ОН); 7.19-7.26 (2H, m, H-4 thienyl + OH);
7.29-7.35 (5H, m, H phenyl); 7.65 (1H, d, J = 3.7, H-5 thienyl);
7.86 (1H, d, J = 4.9, H-3 thienyl); 10.85 (1H, br. s, NH)
4f
1.64-1.87 (2Н, m, СН2); 2.13 (3Н, m, СН3); 2.14-2.19 (2Н, m, СН2);
2.32-2.54 (2Н, m, СН2); 5.73 (1Н, br. s, СН-ОН); 6.19 (1Н, br. s, СН-ОН);
7.19-7.41 (5Н, m, H phenyl); 10.96 (1Н, br. s, NH)
5a
1.56-1.71 (2Н, m, СН2); 1.75-1.89 (2Н, m, СН2); 2.10 (3Н, s, СН3);
2.14-2.24 (2Н, m, СН2); 2.40 (3Н, s, СН3); 2.72-2.87 (4Н, m, 2СН2СО);
2.89-3.00 (2Н, m, СН2); 7.15-7.40 (7Н, m, H phenyl); 7.79 (2Н, d, J = 8.1, H phenyl)
25

TABLE 2 (continued)
1
2
5b
5c
5d
6a
2.01 (3Н, s, СН3); 2.21-2.38 (5Н, m, СН2 + СН3); 2.42-2.53 (2Н, m, СН2);
2.71-2.89 (4Н, m, 2СН2); 2.93-3.06 (2Н, m, СН2); 7.21-7.48 (7Н, m, Н phenyl);
7.20 (2Н, d, J = 8.1, H phenyl)
1.51-1.66 (2Н, m, СН2); 1.67-1.81 (2Н, m, СН2); 2.00 (3Н, s, СН3СО);
2.08-2.21 (2Н, m, СН2); 2.63 (3Н, s, СН3); 2.66-2.77 (4Н, m, 2СН2СО);
2.88-3.02 (2Н, m, СН2); 7.25-7.49 (5Н, m, H phenyl)
2.03 (3Н, s, СН3); 2.21-2.39 (2Н, m, СН2); 2.41-2.55 (2Н, m, СН2); 2.64 (3Н, s, СН3);
2.72-2.91 (4Н, m, 2СН2); 3.01-3.14 (2Н, m, СН2); 7.29-7.38 (3Н, m, Н phenyl);
7.40-7.51 (2Н, m, Н phenyl)
1.56-1.85 (4Н, m, 2СН2); 2.08 (3Н, s, СН3); 2.23-2.39 (2Н, m, СН2);
2.60-3.08 (6Н, 2СН2СО + СН2); 5.54 (1Н, s, СН); 7.13 (2H, d, J = 6.8, H phenyl);
7.19-7.37 (3H, m, H phenyl); 7.41-7.65 (3H, m, H phenyl); 7.77 (2H, d, J = 6.8, H phenyl);
10.03 (1Н, br. s, NH)
6b
7
1.55-1.84 (4Н, m, 2СН2); 2.08 (3Н, s, СН3); 2.17-2.35 (2Н, m, СН2);
2.56-3.00 (6Н, 2СН2СО + СН2); 5.46 (1Н, s, СН); 7.05-7.36 (6Н, m, H phenyl+ Н-4 thienyl);
7.73 (1Н, d, J = 2.9, Н-5 thienyl); 7.86 (1Н, d, J = 4.4, Н-3 thienyl); 10.01 (1Н, br. s, NH)
1.64-1.86 (4Н, m, 2СН2); 2.43-2.55 (2Н, m, СН2); 2.56-2.70 (2Н, m, СН2);
6.57 (1Н, s, Н-3 thienyl); 7.48-7.63 (3Н, m, H phenyl); 7.91-8.01 (2Н, m, H phenyl);
9.42 (1Н, br. s, NH)
Thus, we have studied the behavior of furylmethane structures, obtained on the basis of 2-amino-
3-benzoylthiophene, under the influence of acids; it was established that the direction of the reaction and the
structure of the products are influenced by the nature of the protecting group. Conditions were proposed for the
production of new derivatives of thieno[2,3-b]pyrrole based on the recyclization of 2-R-amino-3-furfuryl-
thiophenes.
EXPERIMENTAL
1
The H NMR spectra were recorded in DMSO-d6 on Bruker AC-200 (200 MHz) and Bruker AM300
(300 MHz) instruments with TMS as internal standard. Thin-layer chromatography was conducted on Silufol
UV-254 and Sorbfil (Sorbpolimer) plates with iodine vapor, bromine, and 2,4-dinitrophenylhydrazine as
developer. For column chromatography we used silica gel of grade KSK (Ltd. Sorbpolimer) (50-100 μ).
3-Benzoyl-2-tosylamidothiophenes 3a,e. TsCl (1.04 ml, 13 mmol) was added in portions (1.04 g,
5.5 mmol) to a mixture of the amino ketone 1a,b (3.9 mmol) and pyridine. The crystals of the initial compound
gradually dissolved, and the reaction mixture became hot. When all the TsCl had been added the reaction
mixture was kept at 45-55°C for 40 min. It was then poured into water, and the excess of pyridine was
neutralized with oxalic acid. The precipitate was filtered off, dried, and recrystallized from a CH2Cl2–petroleum
ether mixture. The tosyl derivatives 3a,e were obtained in the form of pale-yellow crystals with yields of 1.34
and 1.32 g respectively.
Acylation of Compounds 1a,b (General Method). Respective carboxylic acid chloride (12 mmol) was
added to a solution of the amino ketone 1a,b (10 mmol) in toluene (30 ml). The mixture was boiled for 2 h 30
min until the reaction had finished (monitored by TLC). The obtained solution was evaporated under vacuum to
half the initial volume, petroleum ether was added, and the solution was left to crystallize. The crystals that
separated were purified by recrystallization from a CH2Cl2–petroleum ether mixture, and the acylation products
3c,d were obtained in the form of bright-yellow crystals.
N-Acetyl Derivatives 3b,f. These derivatives were synthesized in a similar way with acetyl chloride
(20 mmol). The reaction took 2 h.
26

TABLE 3. The Mass Spectra of Compounds 2-7
Com-
pound
m/z (Irel, %)
477 [M]+ (5), 323 (11), 322 (98), 295 (19), 280 (16), 279 (12), 278 (21), 264 (12),
2a
240 (26), 91 (27), 65 (13), 43 (18)
365 [M]+ (50), 323 (41), 322 (77), 308 (22), 307 (44), 306 (66), 295 (20), 291 (13),
2b
290 (29), 288 (18), 282 (15), 281 (30), 280 (28), 279 (28), 278 (16), 267 (23), 266 (100),
265 (28), 264 (60), 263 (40), 254 (15), 253 (27), 252 (22), 251 (23), 250 (16), 249 (19),
247 (54), 246 (69), 244 (18), 242 (26), 241 (56), 240 (81), 231 (18), 225 (28), 212 (20),
205 (14), 198 (16), 178 (12), 171 (24), 152 (12), 91 (14), 43 (22)
427 [M]+ (100), 323 (13), 322 (50), 307 (10), 306 (21), 264 (11), 240 (10), 106 (25),
2c
105 (95), 95 (34), 77 (85), 57 (11), 43 (32), 41 (11)
433 [M]+ (25), 390 (33), 111 (100), 79 (14), 65 (15), 60 (16), 59 (45), 58 (11), 56 (16),
2d
55 (19), 45 (23), 43 (56)
463 [M]+ (8), 309 (16), 308 (99), 281 (21), 266 (18), 265 (11), 264 (24), 250 (12),
2e
226 (28), 91 (30), 65 (15), 43 (28)
351 [M]+ (92), 309 (13), 308 (43), 293 (20), 292 (24), 276 (21), 267 (13), 266 (17),
2f
264 (12), 253 (13), 233 (12), 232 (28), 228 (10), 227 (40), 226 (100), 217 (12), 171 (16),
128 (12), 115 (12), 101 (21), 77 (16), 45 (15), 43 (52), 42 (37), 41 (22)
411 [M]+ (8), 257 (26), 256 (99), 229 (10), 228 (51), 222 (12), 195 (11), 105 (99), 92 (12),
3a
91 (68), 78 (13), 77 (100), 65 (42), 62 (13), 51 (28), 39 (24)
299 [M]+ (32), 258 (13), 257 (82), 256 (100), 229 (11), 228 (39), 200 (10), 105 (28), 59 (12),
3b
43 (28), 42 (14)
361 [M]+ (30), 256 (21), 228 (11), 106 (46), 105 (100), 104 (10), 101 (10), 77 (68), 59 (10),
3c
51 (15), 43 (25)
367 [M]+ (73), 262 (11), 256 (17), 112 (17), 111 (100), 105 (18), 82 (14), 77 (1), 59 (15),
3d
43 (22), 42 (15)
397 [M]+ (2), 242 (37), 105 (88), 91 (52), 78 (12), 77 (100), 65 (33), 51 (24), 44 (19),
3e
39 (18)
285 [M]+ (26), 244 (19), 243 (100), 242 (54), 214 (25), 182 (10), 165 (15), 138 (14),
3f
106 (32), 105 (36), 77 (20), 76 (36), 51 (14), 43 (26)
301 [M]+ (5), 283 (13), 242 (17), 241 (55), 240 (100), 239 (15), 212 (25), 211 (18),
4b
198 (62), 166 (10), 127 (10), 115 (10), 91 (16), 76 (37), 71 (11), 60 (16), 59 (50), 55 (21),
51 (34), 44 (25), 43 (60), 42 (22)
363 [M]+ (4), 347 (10), 346 (17), 345 (73), 242 (18), 241 (29), 240 (57), 239 (14),
4c
198 (19), 106 (33), 105 (100), 77 (65), 59 (20), 55 (10), 43 (32), 42 (19), 39 (13)
351 [M18] (39), 241 (17), 240 (72), 239 (14), 198 (38), 113 (14), 112 (16), 111 (100),
4d
4f
83 (21), 77 (18), 43 (41)
287 [M]+ (9), 269 (17), 228 (19), 227 (61), 226 (100), 225 (17), 198 (21), 197 (14),
184 (64), 152 (13), 115 (10), 91 (14), 76 (33), 71 (13), 60 (12), 59 (54), 55 (23), 51 (33),
44 (20), 43 (63), 42 (16)
477 [M]+ (33), 324 (23), 323 (50), 322 (100), 280 (27), 279 (19), 267 (132), 266 (56),
265 (18), 264 (28), 262 (19), 251 (14), 203 (15), 156 (13), 152 (16), 124 (16), 101 (55),
98 (17), 92 (20), 91 (56), 76 (21), 70 (15), 65 (43), 63 (14), 60 (22), 59 (85), 58 (30), 57 (57),
56 (28), 55 (43), 53 (26), 51 (24), 45 (30), 43 (67)
5a
5b
463 [M]+ (71), 311 (15), 310 (13), 309 (84), 308 (65), 307 (27), 291 (33), 290 (13),
289 (21), 276 (15), 268 (10), 267 (49), 266 (95), 265 (73), 264 (33), 263 (14), 253 (51),
252 (64), 251 (86), 250 (79), 249 (21), 248 (15), 239 (16), 238 (25), 236 (20), 235 (12),
233 (48), 232 (30), 231 (33), 230 (19), 218 (27), 217 (13), 216 (20), 204 (19), 190 (25),
189 (13), 178 (25), 177 (15), 165 (25), 105 (31), 91 (100), 76 (51), 65 (47), 64 (20),
59 (14), 48 (13), 45 (34), 43 (58), 42 (19), 41 (16)
365 [M]+ (39), 324 (15), 323 (45), 305 (15), 280 (18), 267 (19), 266 (100), 264 (14),
250 (11), 238 (27), 237 (10), 204 (11), 43 (43)
5c
351 [M]+ (35), 309 (30), 266 (17), 254 (13), 253 (32), 252 (100), 251 (22), 250 (11),
224 (12), 190 (13), 177 (11), 165 (19), 116 (10), 105 (32), 76 (23), 59 (19), 55 (11),
43 (50), 42 (32), 41 (17)
5d
445 [M]+ (27), 348 (13), 347 (24), 346 (100), 240 (12), 111 (18), 106 (23), 105 (99),
101 (16), 99 (13), 95 (14), 82 (11), 77 (79), 71 (12), 59 (40), 55 (10), 43 (34), 42 (21),
41 (13), 39 (16)
6a
451 [M]+ (48), 353 (22), 352 (69), 268 (36), 242 (11), 212 (12), 113 (25), 112 (19),
111 (100), 99 (17), 59 (14), 55 (12), 45 (12), 43 (28)
6b
7
258 [M]+ (14), 257 (74), 152 (10), 118 (10), 106 (55), 105 (100), 51 (36), 45 (11), 42 (13),
41 (15)
27

3-Hydroxy(phenyl)methyl-2-tosylamidothiophenes 4a,e. Finely ground NaBH4 (0.76 g, 20 mmol)
was added in portions to a stirred solution of the ketone 3a,e (5 mmol) in a mixture of THF (8 ml) and ethanol
(20 ml) with cooling in iced water. The reaction mixture was stirred on a cooling bath for 40-60 min until the
initial ketone had completely disappeared (monitored by TLC), after which the mixture was poured into water
(100 ml), and ethyl acetate (10 ml) was added. The oil that separated was extracted with ethyl acetate (3×30 ml).
The combined extracts were dried with Na2SO4, the solvent was distilled under vacuum, and the alcohols 4a,e
were obtained in the form of oils with yields of 1.83 and 1.81 g respectively. Since the substances are very labile
and decompose during storage and during attempts at purification they were used in the next stage immediately
after preparation and without further purification.
Reduction of Compounds 3b-d,f (General Method). Finely ground NaBH4 (0.76 g, 20 mmol) was added
in portions to a solution of the ketone 3b-d,f (5 mmol) in a mixture of THF (8 ml) and ethanol (20 ml). The reaction
mixture was then brought to boiling and left at room temperature for 15 min. The mixture was then poured into cold
water (100 ml), phosphoric acid was added to give a weakly acidic medium (pH ~6), and the mixture was stirred
until a precipitate separated. The precipitate was filtered off, dried, and recrystallized from a mixture of ethyl acetate
and petroleum ether. The alcohols 4b-d,f were obtained in the form of pale-yellow crystals.
Synthesis of Furylmethanes 2a-f (General Method). Anhydrous sodium sulfate (1.0 g), 2-methylfuran
(0.27 ml, 3 mmol), and trifluoroacetic acid (0.6 ml) were added to a solution of the alcohol 4a-f (3 mmol) in
CH2Cl2 (70 ml). The reaction mixture was kept at room temperature for 45 min-4.0 h until the alcohol 4 had
completely disappeared while the reaction was monitored by TLC. At the end of the reaction the solution was
decanted, washed with a cold solution of NaHCO3, and dried with anhydrous Na2SO4. The solvent was
evaporated to a third of the volume under vacuum, petroleum ether was added, and the mixture was left to
crystallize. The precipitate that separated was recrystallized from a mixture of CH2Cl2 and petroleum ether.
Compounds 2a-f were obtained in the form of white crystals.
Reaction of Compounds 2a-f with Hydrochloric Acid in Glacial Acetic Acid. Hydrochloric acid
(3 ml) was added to a solution of the compound 2a-f (3 mmol) in glacial acetic acid (30 ml) The obtained
mixture was kept at 60-65°C until the compound 2a-f had been completely converted (TLC). It was then poured
into iced water (150 ml) and neutralized to pH ~6 with a 20% aqueous solution of NaOH and then with dry
NaHCO3. For compounds 2a,e the crystals that separated were filtered off, dried, and recrystallized from a
mixture of CH2Cl2 and petroleum ether. We obtained 4-(3-phenyl-1-tosyl-4,5,6,7-tetrahydro-1H-[1]benzo-
thieno[2,3-b]pyrrol-2-yl)butan-2-one (5a) (0.98 g) in the form of beige crystals and 4-(3-phenyl-1-tosyl-
cyclopenta[4,5]thieno-[2,3-b]pyrrol-2-yl)butan-2-one (5b) (1.0 g) in the form of pinkish crystals.
In the case of compounds 2b-d,f the mixture after neutralization was extracted with ethyl acetate
(5×20 ml), and the extracts were dried with Na2SO4. The solvent was evaporated under vacuum, and the residues
were chromatographed on silica gel with the following systems as eluents: CH2Cl2–petroleum ether 2:1
(for 2b,f); CH2Cl2–acetone–petroleum ether 4:0.5:10 (for 2c); CH2Cl2–acetone–petroleum ether 11:1:8 (for 2d).
The yields, physicochemical constants, and spectral characteristics of compounds 5a-d, 6a,b, and 7 are
given in Tables 1-3.
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A. V. Butin, T. A. Stroganova, I. V. Lodina, and G. D. Krapivin, Tetrahedron Lett., 42, 2031 (2001).
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28