Introduction of taurine (2-aminoethanesulfonic acid) as a green bio-organic catalyst for the promotion of organic reactions under green conditions

Farhad Shirini*a and Nader Daneshvarb
aDepartment of Chemistry, College of Science, University of Guilan, 41335, Rasht, Iran. E-mail:; Fax: +98 131 3233262; Tel: +98 131 3233262
bDepartment of Chemistry, College of Science, University of Guilan, University Campus 2, Iran. E-mail:

Received 14th June 2016 , Accepted 26th October 2016

First published on 18th November 2016


Taurine (2-aminoethanesulfonic acid), a semi-essential amino acid that exists in the human body and numerous other living creatures, is used as a green bio-organic catalyst for the promotion of the Knoevenagel reaction between aldehydes and malononitrile. In the same way, tetraketones can also be produced through a Knoevenagel reaction, followed by Michael addition. 2-Amino-3-cyano-4H-pyran derivatives are simply prepared via a three-component reaction in the presence of taurine as the catalyst. All these reactions are performed in water, a green solvent. The advantages of using of taurine as the catalyst are it is environmentally friendly, low cost, commercially available, easy to separate from the reaction mixture, and has high reusability. Use of this catalyst results in acceptable reaction times, high yields and high purities of the obtained products without utilizing any organic solvents.


The progress of science has been more and more towards environmentally compatible, or “green” processes, with particular focus on catalysts and other materials in organic chemistry. One aspect of these topics is the application of an alternative reaction medium that is free from the problems associated with the numerous traditional volatile solvents. Using this type of media may also increase the chance of separation and reuse of the catalyst. From the viewpoint of green chemistry, it is better to perform the reactions under solvent-free conditions, but when solvent is necessary, water is the best choice.1 In addition to environmental concerns, chemists prefer to use water as a solvent due to its economic benefits and generally easy separation and work-up conditions. Furthermore, all biological reactions are known to occur in aqueous media. Moreover, numerous organic reactions proceed faster and better in water than in organic solvents.2

2-Aminoethane sulfonic acid, or taurine (Fig. 1), is an amino acid that is found in high concentration in the tissues of animals. It is one of the constituent members of bile, which can be found in the large intestine and its amount in the average is one-tenth percent of the total weight of the human body.3 Taurine appellation refers to its first isolation from ox bile, named Bos taurus.4 The concentration of taurine in mammalian organs is higher in comparison with the other types of the animals; its concentration in insects and arthropods is less than that in mammals, whereas in plants and bacteria, its concentration is negligible.5 Red algae, although not the brown or green ones, contain high levels of taurine and its N-(1-carboxylated) derivatives, but lichens, mushrooms, mosses, and ferns have very low concentrations of this amino acid.6

image file: c6ra15432h-f1.tif
Fig. 1 Taurine.

In comparison with other homologue amino acids, taurine is structurally different. It is a β-amino acid with a sulfonic acid group instead of a carboxylic acid group. This difference increases its acidity, i.e., in the range of mineral acids (pKa = 1.5), compared to carboxylic acid homologues, and unlike those homologues that are not dissociated at biological pH, taurine is in a zwitterionic state at this pH level, which leads to distinct biological properties.7 According to computational investigations, the neutral conformation of taurine exists in the gas phase, whereas its zwitterionic form exists in water media, which is in agreement with the experimental NMR analysis.8

Taurine has been used for many years as an ingredient in energy drinks and nutrient supplements and has many biological properties such as osmoregulation, immunomodulation and bile salt formation.9

Very recently, silica gel supported taurine was used in the oxidation of sulfides to their corresponding disulfides.10 Moreover, to the best of our knowledge, there are no other reports of the catalytic activity of this β-amino acid for organic transformations.

In recent decades, performance of standard chemical reactions in aqueous media has been often considered, with particular focus on carbon–carbon bond forming transformations.11 Several reactions that have been investigated in this capacity are Diels–Alder, Claisen and Aldol condensations, and radical additions.12

The Knoevenagel reaction, i.e., treatment of an aldehyde with an active methylene group reported by Emil Knoevenagel in 1894, is one of the most important and notable reactions for C[double bond, length as m-dash]C bond formation.13 This reaction is suitable for the preparation of alkenes with electron-withdrawing groups and its products can be used as intermediates for many other types of reactions.14

Many conditions have been used to promote the Knoevenagel reaction between aldehydes and malononitrile, including grinding, high pressure, microwaves, and ultrasonics.15 Different types of catalysts have also been utilized; among the most important are cetyltrimethylammonium bromide (CTMAB),16 ReBr(CO)5,17 1,1,3,3-tetramethylguanidium lactate,18 [C4dabco][BF4],19 amine-functionalized polyacrylonitrile fiber,20 Fe3O4 MNPs–guanidine,21 sulfonated carbon/silica composites,22 MP(DNP),23 Na2S/Al2O3,24 silica–L-proline,25 ZnO,26 NixMg1−xFe2O4,27 sodium carbonate,28 hydroxyapatite supported caesium carbonate,29 Tamarindus indica juice,30 L-proline–IL,31 and SiO2–NH4OAc.32

Arylmethylene[bis(3-hydroxy-2-cyclohexene-1-ones)] (tetraketones) firstly were introduced by Merling through the addition of aldehydes with 1,3-diketones via a Knoevenagel reaction followed by a Michael addition.33 These compounds have been extensively used as intermediates for some other important target compounds such as acrilidine diones, thiaxanthenes and xanthene diones.34 Tetraketones have biological activity as antioxidants, lipoxygenases and tyrosinase inhibitors.35 Because of the important properties of these products, several methods have been used to achieve them using various catalysts such as SnCl2/HCl,36 In(OTf)3,37 SmCl3,38 Yb(OTf)3–SiO2 with aniline,39 Fe3O4@SiO2–SO3H,40 PVP-stabilized Ni nanoparticles,41 choline chloride-based deep eutectic,42 nano Fe/NaY zeolite,43 EDDA,44 and Al/MCM-41.45

4H-Pyran and its derivatives have attracted much interests because of their important biological activities, such as anticoagulant, spasmolytic, diuretic, anticancer, antianaphylactin,46 antiallergenic,47 antiproliferative,48 antitumor,49 antibacterial,50 cytotoxic,51 mutagenic52 and sex pheromonal53 activities. These compounds also are present in the structure of some photoactive materials54 and natural products55 and can be used in the synthesis of cosmetics and pigments.56

A large number of catalysts were introduced for the synthesis of 2-amino-3-cyano-4H-pyran derivatives under various conditions; notable among them are hexadecyldimethyl benzyl ammonium bromide,57 1-butyl-3-methyl imidazolium hydroxide,58 2,2,2-trifluoroethanol,59 Ba(OTf)2,60 tetrabutylammonium chloride,61 triazine functionalized ordered mesoporous organosilica,62 tungstic acid functionalized mesoporous SBA-15,63 p-dodecylbenzenesulfonic acid,64 potassium phthalimide,65 red sea sand,66 choline hydroxide,67 IRMOF-3(Zn4O(H2N-TA)3),68 β-cyclodextrins–glycerine,69 tris-hydroxymethylaminomethane,70 squaramide,71 Ce(SO4)2·4H2O,72 poly(vinylpyrrolidonium)hydrogen phosphate,73 L-proline,74 I2,75 and glutamic acid.76


All the chemicals for this study were purchased from Merck, Aldrich, and Fluka Chemical Companies and used without further purification. All the products were separated and characterized by their physical properties in comparison with the reported standards. Both the purity determination of the substrates and reaction monitoring were accomplished by thin layer chromatography (TLC) using SIL G/UV 254 silica gel plates. Melting points were determined using a Buchi B-545 apparatus. FT-IR spectra were obtained by a Perkin-Elmer spectrum BX series spectrophotometer (KBr disks). The 1H NMR and 13C NMR spectra were acquired by a Bruker Avance 400 MHz instrument using deuterated solvents.

General procedure for the Knoevenagel condensation of aldehydes and malononitrile

In a 25 mL round-bottomed flask, a mixture of aldehyde (1.0 mmol), malononitrile (1.1 mmol) and taurine (0.025 g, 20 mol%) in water (2 mL) was heated at a reflux temperature for the appropriate time. After the conversion, which was monitored by TLC, 10 mL of water was added and stirred for 3 minutes. During this time, the product was precipitated and subsequently separated by filtration. The separated product was washed several times with water. After drying, the pure product was obtained; there was no need for further purification and addition of organic solvent was not necessary. Furthermore, water was evaporated from the filtrate to re-obtain the taurine catalyst.

General procedure for the synthesis of tetraketones

In a 25 mL round-bottomed flask, a mixture of aldehyde (1.0 mmol), 1,3-cyclodicarbonyl compound (2.0 mmol) and taurine (0.030 g, 24 mol%) in water (2 mL) was heated at reflux for the appropriate time. After completion of the reaction, which was monitored by TLC, 10 mL of water was added and stirred for 3 minutes. During this time, the product was precipitated and subsequently separated by filtration. The separated product was washed several times with water. After drying, the pure product was obtained; there was no need for further purification and addition of organic solvent was not necessary. Furthermore, water was evaporated from the filtrate to re-obtain the taurine catalyst.

General procedure for the synthesis of 2-amino-4H-chromenes

In a 25 mL round-bottomed flask, a mixture of aldehyde (1.0 mmol), 1,3-cyclodicarbonyl compound (1.0 mmol), malononitrile, (1.1 mmol) and taurine (0.030 g, 28 mol%) in water (2 mL) was heated at reflux for the appropriate time. After the reaction was competed, which was monitored by TLC, 10 mL of water was added and stirred for 3 minutes. During this time, the product was precipitated and subsequently separated by filtration. The separated product was washed several times with water. After drying, the pure product was obtained; there was no need for further purification and addition of organic solvent was not necessary. Furthermore, water was evaporated from the filtrate to re-obtain the taurine catalyst.

Spectroscopic data of the new compounds

2-(4-(Methylthio)benzylidene)malononitrile (1p). IR (KBr, cm−1): 3040, 2217, 1648, 1564, 1094; 1H NMR (400 MHz, DMSO-d6): δ = 2.58 (s, 3H), 7.48 (d, J = 8.4 Hz, 2H), 7.89 (d, J = 8.4 Hz, 2H), 8.42 (s, 1H) ppm; 13C NMR (100 MHz, DMSO-d6): δ = 14.30, 79.10, 114.14, 115.10, 125.87, 127.75, 131.41, 148.92, 160.86 ppm.
2,2′-(3-(2-Nitrophenyl)prop-2-ene-1,1-diyl)bis(3-hydroxy-5,5-dimethylcyclohex-2-en-1-one) (2q). IR (KBr, cm−1): 3445, 3070, 2960, 2868, 1600, 1590, 1519, 1380. 1H NMR (400 MHz, CDCl3): δ = 1.10 (s, 6H), 1.17 (s, 6H), 2.30–244 (m, 8H), 4.98 (m, 1H), 6.39 (dd, J = 16.0, 4.0 Hz, 1H), 6.89 (dd, J = 16.0, 2.4 Hz, 1H), 7.35 (dt, J = 8.0, 1.6 Hz, 1H), 7.56 (dt, J = 8.0, 1.2 Hz, 1H), 7.94 (dd, J = 8.0, 1.2 Hz, 1H), 11.27 (br, 1H), 12.12 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ = 20.86, 29.73, 31.42, 31.44, 46.20, 46.83, 115.96, 124.53, 125.37, 127.72, 128.80, 133.12, 133.16, 134.64, 147.34, 189.43, 190.05 ppm.
2-Amino-4-(4-(methylthio)phenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (3y). IR (KBr, cm−1): 3318, 3171, 2961, 2913, 2194, 1682, 1647, 1364; 1H NMR (400 MHz, DMSO-d6): δ = 1.92–2.00 (m, 2H), 2.24–2.34 (m, 2H), 2.35 (s, 1H), 2.61–2.63 (m, 2H), 4.16 (s, 1H), 7.08 (s, 2H), 7.02 (d, J = 8.4 Hz, 2H), 7.10 (d, J = 8.4 Hz, 2H) ppm; 13C NMR (100 MHz, DMSO-d6): δ = 15.29, 20.29, 26.95, 35.46, 36.81, 58.50, 114.17, 120.23, 126.53, 128.31, 136.53, 142.09, 158.88, 158.92, 164.87, 196.35 ppm.

Results and discussion

In recent years, introduction of sulfonic acid based catalysts for the promotion of organic transformations has been an important part of our ongoing research program.77,78 In continuation of these studies, we were interested in investigating the applicability of taurine, a natural, green and commercially available amino acid containing a sulfonic acid group, in the acceleration of organic reactions. The Knoevenagel reaction was selected as the model reaction. In the optimization study, the reaction was initially carried out in the absence of solvent and catalyst and only a little product was obtained. This result was achieved again even when the catalyst was used under solvent-free conditions. Then, the reaction was tested in chloroform, acetonitrile and ethanol with no significant change in the progress of the reaction. In continue the reaction was studied in water as the solvent. The progress of the reaction at room temperature in water was slow, and became even slower as it proceeded; however, the rate was greatly increased at reflux, so the decision was made to pursue these conditions instead. At the end of this study, the optimal amount of catalyst was determined by systematically altering the amount of taurine (Table 1). The Knoevenagel reaction was then performed with various aromatic aldehydes and malononitrile using the optimized amount of the catalyst (20 mol%, 24 mg) in water and under reflux conditions (Scheme 1). As shown in Table 2, various types of aldehydes containing electron-donating and electron-withdrawing groups were successfully converted to the corresponding nitrile products. No distinct substitution effect was observed for this reaction. The isolated products were extremely pure without the need for any costly purification steps, which can be expensive in terms of time, materials and overall yield.
Table 1 Optimization of the conditions for the Knoevenagel reaction [1g]a
Entry Catalyst (mol%) Solvent Temp. Time (min) Yieldb (%)
a Reaction conditions: 4-chlorobenzaldehyde (1.0 mmol), malononitrile (1.1 mmol), solvent (2 mL) and required amount of catalyst.b The yields are related to the isolated products.c The reaction was not completed.
1 90 °C 90 Tracec
2 24 90 °C 90 Tracec
3 24 CHCl3 Reflux 90 Tracec
4 12 EtOH Reflux 90 Tracec
5 24 EtOH Reflux 90 Tracec
6 24 CH3CN Reflux 90 Tracec
7 12 H2O RT 90 Tracec
8 24 H2O RT 90 87
9 16 H2O Reflux 13 91
10 20 H2O Reflux 7 98
11 24 H2O Reflux 6 95
12 24 H2O/EtOH (3[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 20 86

image file: c6ra15432h-s1.tif
Scheme 1 The Knoevenagel reaction between aldehydes and malononitrile.
Table 2 The Knoevenagel reaction of aldehydes and malononitrile in the presence of taurine as the catalyst in water medium
Entry Aldehyde Product Symbol Time (min) Yielda (%) Mp (°C)
(Obs.) (Lit.)
a The yields are related to the isolated products.
1 image file: c6ra15432h-u1.tif image file: c6ra15432h-u2.tif 1a 14 86 82–83 82–84 (ref. 16)
2 image file: c6ra15432h-u3.tif image file: c6ra15432h-u4.tif 1b 11 94 92–93 93–94 (ref. 27)
3 image file: c6ra15432h-u5.tif image file: c6ra15432h-u6.tif 1c 9 96 138–140 139–140 (ref. 21)
4 image file: c6ra15432h-u7.tif image file: c6ra15432h-u8.tif 1d 18 90 81–82 80 (ref. 24)
5 image file: c6ra15432h-u9.tif image file: c6ra15432h-u10.tif 1e 15 87 99–101 98–99 (ref. 29)
6 image file: c6ra15432h-u11.tif image file: c6ra15432h-u12.tif 1f 10 93 103–105 103–105 (ref. 27)
7 image file: c6ra15432h-u13.tif image file: c6ra15432h-u14.tif 1g 7 98 161–163 161–162 (ref. 27)
8 image file: c6ra15432h-u15.tif image file: c6ra15432h-u16.tif 1h 9 96 156–158 159–160 (ref. 21)
9 image file: c6ra15432h-u17.tif image file: c6ra15432h-u18.tif 1i 12 92 122–124 122–124 (ref. 28)
10 image file: c6ra15432h-u19.tif image file: c6ra15432h-u20.tif 1j 15 94 161–163 157–160 (ref. 22)
11 image file: c6ra15432h-u21.tif image file: c6ra15432h-u22.tif 1k 20 89 115–117 112–114 (ref. 22)
12 image file: c6ra15432h-u23.tif image file: c6ra15432h-u24.tif 1l 14 91 186–188 185–187 (ref. 27)
13 image file: c6ra15432h-u25.tif image file: c6ra15432h-u26.tif 1m 10 93 136–137 137–138 (ref. 24)
14 image file: c6ra15432h-u27.tif image file: c6ra15432h-u28.tif 1n 8 94 295–297 298–300 (ref. 30)
15 image file: c6ra15432h-u29.tif image file: c6ra15432h-u30.tif 1o 10 86 125–127 124–126 (ref. 22)
16 image file: c6ra15432h-u31.tif image file: c6ra15432h-u32.tif 1p 6 97 155–157 New product

Since taurine is soluble in water, it was easily separated from the products by simple filtration. The filtered solution could be reused in the same reaction without significant loss of catalytic activity. This procedure was repeated six times for the model reaction; each time, the cycle was completed with no significant change in reaction time or yield. During the recycling studies, the product was separated and its melting point was verified after every run to ensure that the purity remained excellent (Fig. 2). It should be mentioned that since the purity of most of the derivatives was too high, we preferred not to use any organic solvent at all; thus, the melting points in this work are related to the non-recrystallized products.

image file: c6ra15432h-f2.tif
Fig. 2 Reusability of taurine in the model reactions.

Next, the efficiency of taurine for promoting the synthesis of tetraketone derivatives was investigated via the Knoevenagel reaction, followed by Michael addition of an aldehyde with two equivalents of dimedone or 1,3-cyclohexanedione (Scheme 2).

image file: c6ra15432h-s2.tif
Scheme 2 Synthesis of tetraketones.

It should be mentioned that taurine is only suitable to catalyze formation of open chain xanthenes in water and any effort to achieve closed chain xanthenes as single products using this catalyst was not successful.

Only a small amount of product was formed in the absence of a catalyst and solvent at the first step of the optimization of the conditions. When the catalyst was used under solvent-free conditions, a mixture of the products was achieved at different temperatures. As shown in Table 3, the reaction was tested in different solvents and conditions to determine the optimum conditions (entry 10). Furthermore, various aldehydes were used to prepare diverse tetraketone structures. The aldehydes selected for this purpose produced generally high yields of the desired products with acceptable reaction times and do not require further purification (Table 4). Just like the previous reaction, reusability of the catalyst was studied by selecting a typical reaction and using the catalyst-containing filtrate solution in a new reaction mixture. The process showed good reusability over 6 cycles (Fig. 2).

Table 3 Optimization of the conditions for the synthesis of tetraketones [2g]a
Entry Catalyst (mol%) Solvent Temp. Time (min) Yieldb (%)
a Reaction conditions: 4-chlorobenzaldehyde (1.0 mmol), dimedone (2.0 mmol), solvent (2 mL) and required amount of the catalyst.b The yields are related to the isolated products.c The reaction was not completed.
1 90 °C 120 Tracec
2 24 60–90 °C 120 Mixturec
3 24 CHCl3 Reflux 120 Tracec
4 12 EtOH Reflux 120 Tracec
5 24 EtOH Reflux 120 30c
6 24 CH3CN Reflux 120 Tracec
7 12 H2O RT 120 20c
8 24 H2O RT 120 35c
9 16 H2O Reflux 33 91
10 24 H2O Reflux 20 96
11 28 H2O Reflux 17 92
12 20 H2O/EtOH (3[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 30 83

Table 4 Synthesis of tetraketones in the presence of taurine catalyst in water
Entry Aldehyde Product Symbol Time (min) Yielda (%) Mp (°C)
(Obs.) (Lit.)
a The yields are related to the isolated products.
1 image file: c6ra15432h-u33.tif image file: c6ra15432h-u34.tif 2a 10 95 181–183 185 (ref. 42)
2 image file: c6ra15432h-u35.tif image file: c6ra15432h-u36.tif 2b 15 93 194–196 199–200 (ref. 43)
3 image file: c6ra15432h-u37.tif image file: c6ra15432h-u38.tif 2c 10 92 242–243 244–246 (ref. 38)
4 image file: c6ra15432h-u39.tif image file: c6ra15432h-u40.tif 2d 25 87 181–183 184–186 (ref. 43)
5 image file: c6ra15432h-u41.tif image file: c6ra15432h-u42.tif 2e 20 91 209–211 208–209 (ref. 40)
6 image file: c6ra15432h-u43.tif image file: c6ra15432h-u44.tif 2f 25 94 195–197 197–199 (ref. 40)
7 image file: c6ra15432h-u45.tif image file: c6ra15432h-u46.tif 2g 20 97 139–141 138–141 (ref. 42)
8 image file: c6ra15432h-u47.tif image file: c6ra15432h-u48.tif 2h 15 96 159–161 154–156 (ref. 43)
9 image file: c6ra15432h-u49.tif image file: c6ra15432h-u50.tif 2i 15 90 183–185 184–186 (ref. 43)
10 image file: c6ra15432h-u51.tif image file: c6ra15432h-u52.tif 2j 45 91 185–187 188–190 (ref. 43)
11 image file: c6ra15432h-u53.tif image file: c6ra15432h-u54.tif 2k 15 90 142–144 146–148 (ref. 38)
12 image file: c6ra15432h-u55.tif image file: c6ra15432h-u56.tif 2l 20 95 182–183 180 (ref. 40)
13 image file: c6ra15432h-u57.tif image file: c6ra15432h-u58.tif 2m 25 85 133–135 132 (ref. 41)
14 image file: c6ra15432h-u59.tif image file: c6ra15432h-u60.tif 2n 25 85 220–221 225 (ref. 42)
15 image file: c6ra15432h-u61.tif image file: c6ra15432h-u62.tif 2o 15 92 151–153 146 (ref. 41)
16 image file: c6ra15432h-u63.tif image file: c6ra15432h-u64.tif 2p 30 92 215–218 213–215 (ref. 38)
17 image file: c6ra15432h-u65.tif image file: c6ra15432h-u66.tif 2q 45 93 174–176 New product
18 image file: c6ra15432h-u67.tif image file: c6ra15432h-u68.tif 2r 15 89 219–220 214–216 (ref. 43)
19 image file: c6ra15432h-u69.tif image file: c6ra15432h-u70.tif 2s 20 93 203–205 199–200 (ref. 42)
20 image file: c6ra15432h-u71.tif image file: c6ra15432h-u72.tif 2t 30 96 207–209 209–211 (ref. 36)
21 image file: c6ra15432h-u73.tif image file: c6ra15432h-u74.tif 2u 25 91 199–200 201–203 (ref. 43)
22 image file: c6ra15432h-u75.tif image file: c6ra15432h-u76.tif 2v 30 90 189–191 190–191 (ref. 39)

Ultimately, a one-pot, three-component reaction system was designed containing an aldehyde, either dimedone or 1,3-cyclohexanedione, and malonitrile, to test the ability of taurine to catalyze the formation of 2-amino-3-cyano-4H-pyran derivatives.

Optimization of the conditions was performed using a typical reaction of 4-chlorobenzaldehyde, dimedome and malononitrile under a variety of conditions and in the presence of different amounts of taurine as the catalyst. As shown in Table 5, the best results were obtained in refluxing water using 35 mg (28 mol%) catalyst (entry 10).

Table 5 Optimization of the conditions for the synthesis of 2-amino-3-cyano-4H-pyran derivatives [3i]a
Entry Catalyst (mol%) Solvent Temp. Time (min) Yieldb (%)
a Reaction conditions: 4-chlorobenzaldehyde (1.0 mmol), malononitrile (1.1 mmol) and dimedone (1.0 mmol), solvent (2 mL) and required amount of the catalyst.b The yields are related to the isolated products.c The reaction was not completed.
1 90 °C 120 Tracec
2 24 60–90 °C 120 Tracec
3 24 CHCl3 Reflux 120 Tracec
4 12 EtOH Reflux 120 Tracec
5 24 EtOH Reflux 120 Tracec
6 24 CH3CN Reflux 120 Tracec
7 12 H2O RT 115 90
8 24 H2O RT 90 91
9 16 H2O Reflux 65 90
10 28 H2O Reflux 30 97
11 32 H2O Reflux 26 94
12 28 H2O/EtOH (3[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 45 88

After optimization of the reaction conditions (Scheme 3), different types of aldehydes containing electron-donating and electron-withdrawing groups were subjected to the same reaction. The results showed that all types of aldehydes performed well to give the corresponding products in good to excellent yields.

image file: c6ra15432h-s3.tif
Scheme 3 Synthesis of 2-amino-3-cyano-4H-pyran derivatives.

1,3-Cyclohexanedione was also used in some reactions in place of dimedone and the desired products were obtained (Table 6, entries 20–26). The purity of the isolated products was again such that there was no need for further purification or even recrystallization of the products.

Table 6 Synthesis of 2-amino-3-cyano-4H-pyran derivatives in the presence of taurine as the catalyst in water
Entry Aldehyde Product Symbol Time (min) Yielda (%) Mp (°C)
(Obs.) (Lit.)
a The yields are related to the isolated products.
1 image file: c6ra15432h-u77.tif image file: c6ra15432h-u78.tif 3a 65 82 231–233 232–234 (ref. 73)
2 image file: c6ra15432h-u79.tif image file: c6ra15432h-u80.tif 3b 25 92 209–211 211–213 (ref. 73)
3 image file: c6ra15432h-u81.tif image file: c6ra15432h-u82.tif 3c 15 94 222–225 228 (ref. 69)
4 image file: c6ra15432h-u83.tif image file: c6ra15432h-u84.tif 3d 70 81 204–206 196–199 (ref. 73)
5 image file: c6ra15432h-u85.tif image file: c6ra15432h-u86.tif 3e 45 98 211–213 211–213 (ref. 72)
6 image file: c6ra15432h-u87.tif image file: c6ra15432h-u88.tif 3f 30 96 224–226 228–230 (ref. 72)
7 image file: c6ra15432h-u89.tif image file: c6ra15432h-u90.tif 3g 25 93 287–289 289–291 (ref. 72)
8 image file: c6ra15432h-u91.tif image file: c6ra15432h-u92.tif 3h 35 92 190–192 188–190 (ref. 72)
9 image file: c6ra15432h-u93.tif image file: c6ra15432h-u94.tif 3i 30 97 208–210 208–210 (ref. 73)
10 image file: c6ra15432h-u95.tif image file: c6ra15432h-u96.tif 3j 30 95 203–205 201–203 (ref. 73)
11 image file: c6ra15432h-u97.tif image file: c6ra15432h-u98.tif 3k 25 97 210–212 214–215 (ref. 73)
12 image file: c6ra15432h-u99.tif image file: c6ra15432h-u100.tif 3l 30 96 180–182 181–183 (ref. 73)
13 image file: c6ra15432h-u101.tif image file: c6ra15432h-u102.tif 3m 65 91 193–195 196–198 (ref. 70)
14 image file: c6ra15432h-u103.tif image file: c6ra15432h-u104.tif 3n 45 87 217–219 217–219 (ref. 70)
15 image file: c6ra15432h-u105.tif image file: c6ra15432h-u106.tif 3o 50 94 220–222 222–224 (ref. 70)
16 image file: c6ra15432h-u107.tif image file: c6ra15432h-u108.tif 3p 35 93 266–269 270–275 (ref. 77)
17 image file: c6ra15432h-u109.tif image file: c6ra15432h-u110.tif 3q 30 90 223–226 223–225 (ref. 73)
18 image file: c6ra15432h-u111.tif image file: c6ra15432h-u112.tif 3r 60 89 211–212 208–209 (ref. 58)
19 image file: c6ra15432h-u113.tif image file: c6ra15432h-u114.tif 3s 50 93 212–214 212–213 (ref. 79)
20 image file: c6ra15432h-u115.tif image file: c6ra15432h-u116.tif 3t 20 91 209–210 210–212 (ref. 57)
21 image file: c6ra15432h-u117.tif image file: c6ra15432h-u118.tif 3u 50 94 202–204 202–204 (ref. 57)
22 image file: c6ra15432h-u119.tif image file: c6ra15432h-u120.tif 3v 40 93 221–223 224–226 (ref. 57)
23 image file: c6ra15432h-u121.tif image file: c6ra15432h-u122.tif 3w 35 98 237–240 234–235 (ref. 63)
24 image file: c6ra15432h-u123.tif image file: c6ra15432h-u124.tif 3x 45 85 202–204 206–208 (ref. 63)
25 image file: c6ra15432h-u125.tif image file: c6ra15432h-u126.tif 3y 50 92 217–219 New product

As we have mentioned previously, the reusability of the catalyst was investigated in the model reactions for all three transformations studied (products were 1g, 2g and 3i). In each case, six consecutive runs showed excellent reusability (Fig. 2).

Plausible mechanisms for the abovementioned reactions as catalyzed by taurine are shown in Scheme 4. Taurine acts as a bifunctional donor–acceptor reagent in which the aldehyde carbonyl site is activated by taurine and then attacked by the negatively activated methylene group in malononitrile. Elimination of water in the Knoevenagel reaction results in arylidene malononitriles that can be separated by filtration (compounds 1a–1p). Moreover, it is believed that the taurine-activated aldehyde can be attacked by a taurine-enolized β-dicarbonyl. Then, after losing water and forming an arylidene dicarbonyl in the Knoevenagel reaction, this species can react with another enolized β-dicarbonyl, leading to a tetraketone (products 2a–2v). For the three component system, the Knoevenagel product is again formed, followed by Michael addition with a β-dicarbonyl. Lastly, enolization occurs, followed by amine–enamine tautomerization in the presence of taurine to produce the 4H-pyran derivative (products 3a–3y).

image file: c6ra15432h-s4.tif
Scheme 4 The plausible mechanisms of the studied reactions in the presence of taurine.

The results of this study were compared with some existing literature reports in order to better illustrate the utility of taurine in accelerating the reactions under study (Table 7). In each case, the taurine-catalyzed reaction had an advantage wherein it utilized a green catalyst and a nontoxic solvent, featured easy separation of product and catalyst, offered catalyst reusability, and resulted in lower reaction times and higher yields.

Table 7 Comparison between existing literature reports and some of the taurine-catalyzed reactions in the current work
Product Catalyst Amount Conditions Time (min) Yield (%)
a Current work.
image file: c6ra15432h-u127.tif SiO2L-proline25 10 mol% (0.100 g) CH3CN/80 °C 540 95
L-Proline–IL31 30 mol% 80 °C 1440 96
MNPs–guanidine21 0.39 mol% (0.005 g) H2O–PEG/RT 150 96
SiO2–NH4OAc32 0.200 g CH2Cl2/reflux 450 90
HAP–Cs2CO3 (ref. 29) 0.200 g H2O/80 °C 180 86
CTMAB16 0.50 mmol H2O/RT 90 94
ZnO26 0.500 g H2O/RT 90 86
Na2S/Al2O3 (ref. 24) 20 mol% on 0.500 g CH2Cl2/reflux 30 90
Taurinea 20 mol% (0.025 g) H2O/reflux 7 98
image file: c6ra15432h-u128.tif SmCl3 (ref. 38) 20 mol% 120 °C 20 95
EDDA44 30 mol% THF/reflux 240 97
Fe3O4@SiO2–SO3H40 0.010 g H2O/RT 80 83
Al/MCM-41 (ref. 45) 0.100 g EtOH/reflux 120 88
ChCl[thin space (1/6-em)]:[thin space (1/6-em)]urea42 1 mL 80 °C 120 86
Fe/NaY43 0.025 g EtOH/reflux 70 98
Taurinea 24 mol% (0.030 g) H2O/reflux 20 97
image file: c6ra15432h-u129.tif β-Cyclodextrin69 0.227 g Aq glyserin/40 °C 30 90
IRMOF–Zn complex68 4 mol% 60 °C 300 90
[Ch][OH]67 10 mol% H2O/80 °C 60 86
Red sea sand66 0.500 g EtOH/reflux 280 85
Glutamic acid74 20 mol% EtOH/reflux 40 91
DBSA64 20 mol% H2O/reflux 240–420 69
TFE62 2 mL Reflux 300 95
I2 (ref. 75) 10 mol% DMSO/120 °C 210 88
L-Proline76 10 mol% EtOH/reflux 120 72
HDMBAB57 2.4 mol% H2O/80–90 °C 450 90
TBAC61 10 mol% H2O/reflux 120 98
Taurinea 28 mol% (0.035 g) H2O/reflux 30 97


The general advantages of taurine as a catalyst in the studied reactions are as follows: it is non-toxic for humans and other living organisms, it offers ease of separation of products and catalyst, it does not require use of organic solvents, it features excellent catalyst recyclability and reusability, it is highly stable and easy to store, and finally, it is commercially available at a low price. All of these points are in full compliance with the requirements of green chemistry.


We are thankful to the University of Guilan Research Council for partial support of this work.


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Electronic supplementary information (ESI) available: FT-IR, 1H NMR & 13C NMR of new products. See DOI: 10.1039/c6ra15432h

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