Reduction of thiophenes in the presence of sulfuric acid and zinc

Article abstract of DOI:10.1007/s10593-011-0877-y

Alkyl-substituted thiophenes are hydrogenated by the Zn-H ₂SO₄ system to the corresponding 2,5-di- hydrothiophenes and thiophanes. In the case of 2-formyl- and 2-acetylthiophene it was established that in substituted thiophenes simul

Full text of DOI:10.1007/s10593-011-0877-y

Chemistry of Heterocyclic Compounds, Vol. 47, No. 9, December, 2011 (Russian Original Vol. 47, No. 9, September, 2011)
REDUCTION OF THIOPHENES IN THE PRESENCE
OF SULFURIC ACID AND ZINC
F. M. Latypova1*, M. A. Parfenova2, and N. K. Lyapina2
Alkyl-substituted thiophenes are hydrogenated by the Zn–H2SO4 system to the corresponding 2,5-di-
hydrothiophenes and thiophanes. In the case of 2-formyl- and 2-acetylthiophene it was established that
in substituted thiophenes simultaneous reduction of the substituent to an alkyl group occurs in addition
to hydrogenation of the aromatic ring. The optimum conditions for hydrogenation were selected
experimentally.
Keywords: sulfuric acid, thiophene, zinc, alkyl group, chromatography, hydrogenation, reduction.
The hydrogenation of thiophenes with retention of the cyclic skeleton is not an easy task. One of the
most widely used methods is catalytic hydrogenation of thiophenes with molecular hydrogen. The reaction
begins at a temperature above 200°C and pressure of 0.5 MPa. In addition to the desired products the reaction
products contain significant amounts of hydrogen sulfide and hydrocarbons. The yields of thiophene and
hydrogenolysis products increase with increase in the contact time [1-4]. The sulfides of Pd, W, and Mo are the
most effective in activity and selectivity in the hydrogenation of thiophenes. Reaction at 250-300°C and
0.1 MPa in the presence of nickel-containing zeolites leads to high yields of thiophanes, but the activity of the
catalyst decreases significantly after use for 30 min to 1 h [5]. In the case of noncatalytic methods of
hydrogenation such as the Birch method and its modifications low yields of a mixture of the dihydrothiophenes
and pentenethiols are obtained [6-8]. Ionic hydrogenation with the HSiEt3–CF3COOH system, based on
protonation of the substrate in an acidic medium followed by transfer of a hydride ion from the triethylsilane,
gives high yields of thiophane under mild conditions [9, 10]. However, the application of this method is
restricted by the high cost and the poor availability of the reagents. Replacement of the HSiEt3 by Zn leads to a
change of the reaction products; instead of tetrahydrothiophenes the products are 2,5-dihydrothiophenes, which
are well known as biologically active substances whose synthesis involves a number of difficulties [11, 12].
Under the conditions of the proton–electron reduction of thiophenes by the Zn–CF3COOH system the
mechanism of hydrogenation is regarded as the successive transfer of one proton from the acid and two electrons
from the metal [10]. The trifluoroacetic acid is simultaneously a proton donor and a good solvent. From the
practical standpoint, however, it is important to seek new hydrogenation systems using more readily available
acids and concentrated sulfuric acid in particular.
_______
* To whom correspondence should be addressed, e-mail: post@ugaes.ru.
1Ufa State Academy of Economics and Service, 145 Chernyshevskogo St., Ufa 450078, Russia.
2Institute of Organic Chemistry, Ufa Scientific Center of the Russian Academy of Sciences, 71 Oktyabrya Ave.,
Ufa 450054, Russia; e-mail: sulfur@anrb.ru.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1313-1320, September, 2011.
Original article submitted July 8, 2010. Revision submitted July 28, 2011.
1078
0009-3122/11/4709-1078©2011 Springer Science+Business Media, Inc.

The hydrogenation of alkyl-substituted thiophenes 1a-f by the Zn–H2SO4 system leads to the formation
of 2,5-dihydrothiophenes 2a-d and thiophanes 3a-d with a significant preference for the former. The best results
were obtained with part delivery of the Zn dust to a vigorously stirred mixture of the substrate and H2SO4 in
CH2Cl2. This is evidently due to deactivation of the zinc surface in the concentrated acid.
Zn
R1
R
R1
R
R1
+
H2SO4
R
S
S
S
3a–d
2a–d
1a–f
1–3 a–c R = H, a R1= Et, b R1 = Me, c R1 = Pr, d R = R1 = Me;
1e,f R = H, e R1 = CHO, f R1 = COMe
The hydrogenation of 2-ethylthiophene 1a hardly occurs at all in 60% H2SO4. By raising the acidity to
89% it was possible to increase the yield of 2-ethyl-2,5-dihydrothiophene (2a) to 70%. Further increase in the
concentration of the acid to 90% reduced the yield of compound 2a to 38% and increased the yield of 2-ethyl-
thiophane (3a) to 20% (Table 1). Under the conditions of ionic hydrogenation the reaction requires the
formation of a sufficient quantity of carbocations in the reaction medium, and this is obviously not possible at
low concentrations of H2SO4 [8]. The protonation of the substrate becomes stronger as the concentration of the
acid is increased, and the yield of the hydrogenation products is then increased. With high concentrations of
sulfuric acid (>94%), however, there is a sharp reduction in the yield of the hydrogenated products, which is
evidently due to acceleration of the side processes.
The products were identified on the basis of GLC-MS data. Fractional distillation of the products from
the hydrogenation of compound 1a led to a mixture giving two GLC-MS peaks: m/z 114 and m/z 116. In all
probability the first peak corresponds to 2-ethyl-2,5-dihydrothiophene (2a) (M = 114) and the second to 2-ethyl-
thiophane (3a) (M = 116). In the Raman scattering spectrum of the isolated product corresponding to the first
peak there is a strong absorption band in the region of 1638 cm−1, which coincides with the absorption band of
the C=C bond in 2-ethyl-2,5-dihydrothiophene [13].
The degree of conversion of the initial thiophene can also be affected by change in the solubility of the
H2SO4 in CH2Cl2 in relation to the concentration and acidity of the reaction medium if the reaction takes place in
the organic phase.
With increase in the amount of 89% H2SO4 in the reaction medium from 10 to 30 mol/mol, the yield of
the thiophene 2a is increased to 70% (Fig. 1). In the range from 40 to 60 mol/mol there is a decrease in the yield
of this product and a small increase in the yield of the thiophane 3a, due probably to partial hydrogenation of the
thiophene 2a to the thiophane 3a in the high-acidity medium.
TABLE 1. The Hydrogenation of 2-Ethylthiophene 1a by the Zn–H2SO4
System* at Various Concentrations of H2SO4
Yield, %
Yield, %
Concentration Time,
Concentration Time,
of H2SO4, %
h
of H2SO4, %
h
2а
3а
2а
3а
60
10
10
10
5
0
0
0
2
5
7
91
92
5
5
5
5
5
52
38
15
13
5
14
20
11
8
70
39
57
70
68
86
89
94
96
90
5
100
4
_______
*1a–H2SO4–Zn ratio (mol): 1:30:110; 20°C.
1079

Fig. 1. The dependence of the yield of the products from hydrogenation of 2-ethylthiophene 1a on
the amount of 89% H2SO4. Zn–1a ratio, 110:1, T 20°C, 5 h. 1 – thiophene 2a. 2 – thiophane 3a.
Study of the effect of the amount of zinc on the hydrogenation processes at the optimum ratios of
compound 1a and H2SO4 shows that the highest yield of dihydrothiophene 2a is obtained with a zinc to substrate
ratio of 110:1 (Table 2). The decrease of the yield of dihydrothiophene 2a to 36% with increase of the zinc ratio
to 220:1 is evidently due to the decrease in the acidity of the reaction medium with the excess of solvent added
for better mixing.
Dichloromethane, used in the reaction as solvent, promotes the production of high yields, but it mixes
poorly with sulfuric acid. Realization of the reaction in other solvents (diethyl ether, MeOC12H25, or ethyl
alcohol) that are readily mixable with sulfuric acid showed that the reaction takes place in ethyl alcohol but
gives the desired product in small yield, while in ethers the reaction hardly occurs at all. The high basicity of the
ether evidently leads to a decrease in the acidity of the reaction mixture and a decrease in the concentration of
carbocations. The reaction in sulfuric acid without the solvent is obviously accompanied by secondary processes
such as polymerization, polycondensation, and desulfurization, as a result of which the yield of the desired
products is greatly reduced.
Study of the activity of various samples of zinc dust for the case of 2-propylthiophene (1c) showed that
the yields of compound 2c with the use of Ts-1 and Ts-2 differ little, but in the later case some increase in the
yield of compound 3c is observed. In the employed samples the content of metallic Zn, determined by
iodometric titration, is 92 and 93% respectively, while the data from X-ray fluorescence spectrometry show
insignificant differences between Ts-1 and Ts-2 with respect to Cd (2×10−1 and 5×10−3%) and Cu (5×10−3 and
3×10−1%) contents. The values for the remaining components (Fe, Ca, Pb, etc.) are almost identical [10].
Previous activation of the zinc surface with a 10% solution of HCl has practically no effect on the results of the
reaction. This makes it possible to assume that the increase in the yield of the desired product apparently
depends on the surface area of the zinc dust. The use of coarser zinc filings (1-2 mm) showed that hydrogenation
hardly occurred at all, and only 13% of the starting thiophene 1a remained in the reaction mass. In the strongly
acid medium the metallic surface apparently soon loses activity on account of the formation of a salt film, and
the thiophene in the strongly acid medium undergoes desulfurization, as indicated by the
1080

TABLE 2. Hydrogenation of 2-Ethylthiophene 1a by the Zn–H2SO4
System in CH2Cl2 with Various Zinc Dust–Substrate Ratios*
Yield, %
Molar ratio Zn–1а
Time, h
2а
3а
28:1
60:1
8
8
8
5
5
5
5
15
21
42
70
64
36
70
—
——
90:1
—
5
110:1
130:1
220:1
110:1*2
6
2
4
_______
*1a–H2SO4 (89%) ratio (mol), 1:30; 20°C
*2The acid was added at 0°C.
appearance of the smell of H2S. This hypothesis is supported by the increased degree of hydrogenation when the
zinc dust is added to the reaction mixture in portions, by its large consumption rate, and by the ineffectiveness of
the use of Zn–Hg and Zn–Cu couples in the reaction.
Various alkylthiophenes were subjected to hydrogenation under the optimum conditions obtained for the
thiophene 1a (1a:H2SO4:Zn = 1:30:110). However, the reaction conditions that made it possible to hydrogenate
compound 1a with a high yield of the product 2a were not effective for the other substituted thiophenes. For
each alkylthiophene therefore it was necessary to chose conditions that lead to high yields of the desired
products (Table 3).
Hydrogenation of the thiophene 1b with the Zn–H2SO4 system under the conditions obtained for the
thiophene 1a led to the formation of 2-methyl-2,5-dihydrothiophene (2b) and a small amount of the 2-methyl-
thiophane (3b), i.e., the degree of conversion of compound 1b was significantly reduced. Increase of the molar
ratio of the reagents in relation to the substrate also did not lead to success. An increased yield of the reaction
product 2b is achieved if the H2SO4 is added gradually in portions at reduced temperature (0°C).
During the hydrogenation of 2-propylthiophene 1c, a mixture of 2-propyl-2,5-dihydrothiophene (2c) and
2-propylthiophane (3c) is formed. The mass spectrum of the distillation fraction revealed ions that correspond to
2-propyl-2,5-dihydrothiophene (2c) and 2-propylthiophane (3c). As in the case of 2-ethyl-2,5-dihydro-thiophene
2a, the Raman spectrum of the distilled fraction revealed an absorption band in the region of 1638 cm−1 coinciding
with the absorption band of the isolated C=C bond in 2,5-dihydrothiophene [13]. The 2,5-dimethyl-thiophene
(1d) is hydrogenated by this system with the formation of 2,5-dimethyl-2,5-dihydrothiophene (2d) with a small
amount of 2,5-dimethylthiophane (3d) as impurity. During the hydrogenation of 2,5-dimethyl-thiophene (1d) in
order to obtain better results, it was necessary to double the amount of sulfuric acid and the reaction time, and
this was obviously due to the presence of the two alkyl groups (Table 3).
The hydrogenation of 2-formylthiophene (1e) and 2-acetylthiophene (1f) by the Zn–H2SO4 system leads
to the formation of compounds 2b and 2a respectively, i.e., both the carbonyl group and the thiophene ring are
reduced (Table 4). The hydrogenation of thiophene 1e gives lower yields compared with the compound 1f under
identical conditions. It was possible to increase the yield of the product 2b by reducing the reaction temperature
to 0°C.
The GLC analysis of the reaction mixture at certain time intervals showed that hydrogenation of the
substituted thiophenes 1e and 1f leads to the formation of the intermediate alkylthiophenes 1b and 1a
respectively. During reduction of the thiophene 1e the amount of methylthiophene increases at the beginning of
the reaction but then decreases in the course of time.
1081

Zn
Zn
1e
1f
1b
1a
+
+
H2SO4
Me
Et
Me
Et
H2SO4
S
S
3b
2b
Zn
Zn
H2SO4
H2SO4
S
S
3a
2a
TABLE 3. Hydrogenation of Alkylthiophenes by the Zn–H2SO4 (89%)
System in CH2Cl2, 20°C
1–H2SO4-Zn
molar ratios
Time,
h
Alkyldihydro- Yield,
Yield,
%
Substrate
Alkylthiophane
thiophene
%
1b
1:30:110
1:60:230
1:100:230
1:30:110*
1:30:110
1:30:110*2
1:30:110
1:60:110
1:30:220
1:60:220
5
5
5
5
4
4
8
8
8
8
2b
28
40
37
65
63
63
52
74
58
53
3b
2
4
4
7
1c
2c
3c
4
12
6
1d
2d
3d
6
4
6
_______
*The acid was added at 0°C.
*2Zinc – Ts-2.
Thus, it was shown that the hydrogenation of 2-alkyl- and 2-carbonyl-substituted thiophenes by the
Zn–H2SO4 system in CH2Cl2 results in the formation of the corresponding 2,5-dihydrothiophenes.
TABLE 4. Hydrogenation of Carbonyl-Substituted Thiophenes by the
Zn–H2SO4 System
Alkyl
dihydro-
thiophene
1–H2SO4–molar
Alkyl
thiophane
Substrate
Time, h Т, °С
Yield, %
Yield, %
ratios
1:60:220
1:60:220
1:30:220
1:30:110
1:60:110
1:30:110
1:30:220
1:60:220
6
6
6
6
6
8
8
8
20
0
7
2
5
4
7
7
1
6
6
1e
2b
2a
3b
3a
35
33
32
41
10
50
58
0
0
0
20
20
20
1f
1082

EXPERIMENTAL
1
The H NMR spectra were obtained in carbon tetrachloride on a Bruker WR-200 SY instrument (200
MHz), and the chemical shifts are presented in parts per million with reference to TMS. The mass spectra were
recorded on an AEI MS 1073 chromato-mass spectrometer with an ionization energy of 28.5 eV (I) and on an
MX-1320 mass spectrometer with a heated direct injection system at 70 eV (II). The Raman spectra were
obtained on a Ramanor HG.2S instrument with an argon laser source (514.5 nm). The refractive index was
measured on an IRF-22 refractometer. The GLC analysis was conducted on a Chrom 5 instrument with a flame-
ionization detector. Carrier gas – nitrogen. Columns: 2.7 mm × 3.7 m with 10% PEGA on Risorb BLK 0.2-0.315
mm (version 1); 3 mm × 2.5 m with 20% SKTFT-50-X on Chromaton N-AW 0.16-0.20 mm (version 2);
3 mm × 2.5 m 5% DS 200 on Chromaton N-Super 0.125-0.160 mm (version 3); 3 mm × 1.7 m 15%
pentaerythritol benzoate on Chromaton NAW 0.20-0.25 mm (version 4). Stainless steel columns. The X-ray
fluorescence spectra were obtained on a VRA-2 instrument.
Hydrogenation of 2-Ethylthiophene (1a) at Various Sulfuric Acid Concentrations. To a solution of
compound 1a (0.075 g, 0.68 mmol) in CH2Cl2 (6 ml), zinc dust (2.45 g, 34.47 mmol) was added. Over
10-15 min with constant stirring H2SO4 of the corresponding concentration (2.01 g, 20.52 mmol) was added.
The remaining zinc dust (2.45 g, 37.47 mmol) was added gradually over 30 min. The reaction mixture was
stirred at 20°C for 3 h, decomposed with water, and neutralized with a solution of KOH. The GLC analysis
(version 1, 132°C) showed that the starting compound had reacted completely. The yields of the products were
determined with an internal standard (dodecane). The retention times of compounds 2a and 3a agree with
published data [10]. The results of the analyses are presented in Table 1.
Preparative Hydrogenation of 2-Ethylthiophene (1a). Half the calculated amount of Zn dust (195.8 g,
2.996 mmol) was added to a mixture of 2-ethylthiophene 1a (6.1 g, 54.46 mmol) in CH2Cl2 (300 ml). With
constant stirring 89% H2SO4 (160.1 g, 1.634 mmol) was added dropwise and the remaining Zn dust (195.8 g,
2.996 mmol) was added over 1 h. The reaction mixture was stirred for 8 h until the peak of the starting
compound on the chromatogram had disappeared. The Zn was then filtered off and washed several times with
CH2Cl2, water, and KOH solution. The organic layer was decomposed with water and KOH solution and
extracted with CH2Cl2. The combined organic layer was dried with MgSO4. The residue after removal of the
CH2Cl2 was distilled. Two fractions were collected: at 140-150°C, n20 = 1.4950 (3.72 g, yield 60%) and
D
150-152°C, n20 = 1.4962 (0.17 g, yield 4%). The first fraction contained compound 2a. Mass spectrum (II), m/z
D
(Irel, %): 114 [M]+ (15), 99 [М-СН3]+ (22), 85 [М-C2H5]+ (100), 59 [SC2H3]+ (10), 45 [CH=S]+ (13). The second
fraction contained compound 3a. Mass spectrum, m/z (Irel, %): 116 [M]+ (25), 101 [M-CH3]+ (12), 87 [M-C2H5]+
(100), 59 [SC2H3]+ (10), 45 [SCH]+ (26).
Hydrogenation of 2-Methylthiophene (1b). To a solution of compound 1b (0.078 g, 0.8 mmol) in
CH2Cl2 (5 ml), Zn dust (2.86 g, 44.0 mmol) was added. The mixture was cooled to 0°C, and 89% H2SO4 (1.57 g,
24.0 mmol) was added with constant stirring. The remaining Zn dust (2.86 g, 44.0 mmol) was then added in
portions over 30 min. The reaction mixture was stirred for 3 h and decomposed by the method described above.
The yields of the products 2b and 3b were determined with the method of an internal standard (dodecane) (GLC,
version 1, 119°C).
The hydrogenation of 2-propylthiophene (1c) was conducted similarly to the hydrogenation of
compound 1a. The following were used: compound 1c (3.4 g, 27 mmol), 89% H2SO4 (79.4 g, 0.810 mol), Zn
dust (197.3 g, 3.016 mol), CH2Cl2 (350 ml). Two fractions were collected at 160-171°C (yield 2.05 g, 62%) and
171-172.5°C (yield 0.065 g, 3%). The first fraction contained compound 2c. 1H NMR spectrum, δ, ppm (J, Hz):
0.93 (3Н, m, СН3); 1.42 and 1.67 (4Н, m, СН2СН2); 3.64 (2Н, m, СН2); 4.15 (1Н, m, СН); 5.71 (2Н, m,
НС=СН). Mass spectrum (II), m/z (Irel, %): 128 [M]+ (40), 113 [M-CH3]+ (5), 99 [M-C2H5]+ (8), 85 [М-C3H7]+
(100). The second fraction was compound 3c. Mass spectrum, m/z (Irel, %): 130 [M]+ (22), 115 [M-CH3]+ (1),
101 [M-C2H5]+ (20), 87 [М-C3H7]+ (100), 59 [SC2H3]+ (10), 45 [SCH]+ (22).
1083

The hydrogenation of 2,5-dimethylthiophene (1d) was conducted by the method used for the
hydrogenation of compound 1a. We used compound 1d (0.057 g, 0.508 mmol), 90% H2SO4 (2.987 g,
30.480 mmol), Zn dust (3.654 g, 55.880 mmol), and CH2Cl2 (5 ml). The hydrogenation products 2d and 3d were
identified by GLC–MS (I) (GLC, version 1, 130°C). The compounds corresponding to the first peak (yield
0.034 g, 60%) and the second peak (yield 0.0013 g, 3.7%) were isolated from the benzene extract by preparative
1
GLC. First peak – compound 2d. H NMR spectrum, δ: 1.34 (6Н, m, СН3); 4.27 (2Н, m, СН); 5.57 (2Н, m,
НС=СН). Mass spectrum, m/z (Irel, %): 114 [M]+ (110), 99 [М-CH3]+ (100), 85 [М-С2Н5]+ (11), 59 [SC2H3]+
(30), 45 [SCH]+ (3). Second peak – compound 3d. Mass spectrum, m/z (Irel, %): 116 [M]+ (40), 101 [М-CH3]+
(100), 87 [М-С2Н5]+ (1), 59 [SC2H3]+ (10), 45 [SCH]+ (20).
The hydrogenation of 2-formylthiophene (1e) was conducted by the method used for the
hydrogenation of compound 1b. We used compound 1e (0.087 g, 0.78 mmol), 90% H2SO4 (4.586 g,
46.80 mmol), Zn dust (5.611 g, 85.80 mmol), and CH2Cl2 (5 ml). The reaction time was 6 h. The hydrogenation
products 1e were identified by GLC by the agreement of the retention times of the products and the authentic
compounds on three (in the extreme case, two) columns of different polarity (versions 1, 3, and 4.)
The hydrogenation of 2-acetylthiophene (1f) was conducted by the method used for the hydrogenation
of compound 1a. We used compound 1f (0.101 g, 0.8 mmol), 89% H2SO4 (4.704 g, 48.0 mmol), Zn dust
(11.510 g, 176.0 mmol), and CH2Cl2 (5 ml). The reaction time was 6 h. The hydrogenation products from
compound 1f were identified by GLC–MS (I) and GLC (versions 1, 3, 4). First peak – compound 2a. Mass
spectrum, m/z (Irel, %): 114 [M]+ (15), 99 [М-СН3]+ (22), 85 [М-C2H5]+ (100), 59 [SC2H3]+ (10), 45 [CH=S]+
(13). Second peak – compound 3a. Mass spectrum, m/z (Irel, %): 116 [M]+ (25), 101 [M-CH3]+ (12), 87
[M-C2H5]+ (100), 59 [SC2H3]+ (10), 45 [SCH]+ (26).
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