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A facile and convenient method for synthesis of alkyl thiocyanates under homogeneous phase transfer catalyst conditions
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Chinese Chemical Letters 19 (2008) 1301–1304 www.elsevier.com/locate/cclet
A facile and convenient method for synthesis of alkyl thiocyanates under homogeneous phase transfer catalyst conditions Ali Reza Kiasat *, Rashid Badri, Soheil Sayyahi Chemistry Department, College of Science, Shahid Chamran University, Ahvaz 61357-4-3169, Iran Received 15 May 2008
Abstract A simple and environmentally friendly method is described for the efficient conversion of alkyl halide to alkyl thiocyanate using tetrabutylammonium bromide (TBAB) as a phase transfer catalyst. The reactions occur in water and furnish the corresponding alkyl thiocyanate in high yields. No evidence for the formation of isothiocyanates as by-product of the reaction was observed and the products were obtained in pure form without further purification. # 2008 Ali Reza Kiasat. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Alkyl thiocyanate; Alkyl halide; Tetrabutylammonium bromide; Phase transfer catalyst; Synthesis of alkyl thiocyanates
It is well known that the alkyl thiocyanate [1] plays an important role as an intermediate for the preparation of sulfur-containing organic compounds [2]. They have found a wide variety of applications as insecticides, biocidal, antiasthmatic and starting materials for the preparation of heterocycles. Thiocyanates are also considered to be an important class of compounds found in some anticancer natural products formed by deglycosylation of glucosinolates derived from cruciferous vegetables [3]. Moreover, a-thiocyanatocarbonyl compounds are intermediates for a preferred synthetic route to several types of thiazoles [4]. Thiocyanation is generally carried out via nucleophilic substitution using thiocyanate anions. A number of methods are available for the preparation of alkyl thiocyanates, such as, displacement of leaving groups with thiocyanate ions [5–7]. Thiocyanates can also be obtained from alcohols [8], silyl ethers [9] or amines [10]. However, this displacement frequently requires rather severe reaction conditions because of the low nucleophilicity of the NCS ion. Hence many drawbacks and low yields have been observed for these thiocyanation methodologies [2,11]. In addition, the thiocyanate group is poorly stable when heated or under acidic conditions. Chromatography on silica gel or prolonged heating over 50 8C can cause intramolecular rearrangement to the thermodynamically favored isothiocyanate isomers [12]. Consequently, the development of new methods that are more efficient and lead to convenient procedures and better yields is desirable. Phase transfer catalysts (PTCs) are powerful reagents in chemical transformations [13,14], the characteristics of which include mild reaction conditions, safety, operational simplicity and selectivity. PTCs are often used in nucleophilic displacement reactions to facilitate reactions between organic reactants and ionic inorganic salts [15].
* Corresponding author. E-mail address: [email protected] (A.R. Kiasat). 1001-8417/$ – see front matter # 2008 Ali Reza Kiasat. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2008.07.019
1302
A.R. Kiasat et al. / Chinese Chemical Letters 19 (2008) 1301–1304
Scheme 1.
Although many phase transfer catalysts are known, quaternary salts formed from ammonia are practically important and used in many of organic reactions. In continuation of our investigations on new methodologies for the synthesis of organo-sulfur compounds [16], we report a novel and highly efficient protocol that allows the rapid synthesis of alkyl thiocyanates using TBAB as a phase transfer catalyst under mild and homogeneous condition (Scheme 1). Its high polarity and ability to solubilize both organic and inorganic compounds can result in enhanced reaction rates and can provide higher selectivity compared to conventional methods [17,18]. 1. Experimental All 1H and 13C NMR data were recorded on a Bruker Advanced DPX 400 MHz instrument spectrometer using Me4Si as the internal standard in CDCl3. IR spectra were recorded on a BOMEM MB-Series 1998 FT-IR spectrometer. The purity determination of the products and reaction monitoring were accomplished by TLC on silica gel polygram SILG/UV 254 plates. General procedure: In a typical procedure, a mixture of alkyl halide (1.0 mmol), TBAB (0.5 mmol), KSCN (1.5 mmol) and water (3.0 mL) was placed in a flask and stirred at room temperature or heated (40 8C) for the time specified in Table 1. On completion of the reaction, followed by TLC examination, the mixture allowed to be cold and extracted into ether (3 5 mL). The combined organic layer washed with cold water (3 10 mL), dried over sodium sulfate and filtered. The filtrate was subjected to a vacuum gave the desired product (75–95%). It did not require any column chromatography thus avoiding the possibility of rearrangement. All of the reactions reported here were clean as judged by TLC, FTIR and NMR analysis of the crude reaction mixture. 2. Results and discussions In a first set of experiments, a well-stirred solution of 4-bromo benzyl bromide (1.0 mmol) in H2O (3.0 mL) was treated with KSCN (1-2 mmol) at room temperature in the presence of tetrabutylammonium bromide (0.2– 0.5 mmol) as a phase transfer catalyst. The reaction was monitored by TLC. After some experiments, it was found that the use of 1.5 equiv of KSCN per alkyl halide in the presence of TBAB (0.5 equiv) in water were the best conditions and after stirring for 45 min at room temperature, the clean formation of a product with lower Rf value was observed. We examined the catalytic ability of TBAB for conversion of alkyl halides to alkyl thiocyanate with KSCN in water at room temperature. This catalyst acted very efficiently and it converts different alkyl halides to their corresponding alkyl thiocyanates in high isolated yields. The obtained results of the reaction are given in Table 1. It is noteworthy that no evidence for the formation of Isothiocyanates as by-product of the reaction was observed and the products were obtained in pure form without further purification. 13C resonance of the SCN and NCS groups at 111 and 145 ppm, respectively, are very characteristic for thiocyanate and isothiocyanate functionalities [19]. As shown in Table 1 (entries 7 and 8), this simple method can be efficiently used for preparation of a-thiocyanato carbonyl compounds. As expected the effects of reactant structure on the rate of Bimolecular nucleophilic substitution (SN2) reactions have appeared in entry 12 as no product was observed even 8 h of variously stirring. In conclusion, we have developed an optimized facile thiocyanation under phase transfer catalyst, which requires only a moderate reaction temperature in water. The advantages of present protocol, such as clean reaction profiles, short reaction times, simplicity in operation and the low cost of reagents make this new process an attractive alternative to current methodologies.
A.R. Kiasat et al. / Chinese Chemical Letters 19 (2008) 1301–1304
1303
Table 1 Conversion of alkyl halide to alkyl thiocyanate under PTC in H2O Entry
Alkyl halide
Product
Time (min)
Yielda,b(%)
1
60
85
2
60
80
3
30
90
4
45
85
5
45
80 c
6
45
90 c
7
45
80
8
60
80 c
9
45
80 c
10
180
75
11
30
95c,d
12
a b c d e
–
8e
The NMR and FTIR spectra of all synthesized alkylthiocyanates are in accord with the literature [2,4,11]. Isolated yields. The reaction was performed at 40 8C. GC analysis. 8 h.
–
1304
A.R. Kiasat et al. / Chinese Chemical Letters 19 (2008) 1301–1304
Acknowledgment Partial support for this work by Chamran University Research Council is gratefully acknowledged. References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19]
R.G. Guy, in: S. Patai (Ed.), The Chemistry of the Cyanates and Their Thio Derivatives, Wiley Interscience, New York, 1977, p. 819. O. Prakash, H. Kaur, H. Batra, N. Rani, S.P. Singh, R.M. Moriarty, J. Org. Chem. 66 (2001) 2019. F. Shahidi, in: C.J. Mussinan, M.E. Keelan (Eds.), Sulphur Compounds in Foods, American Chemical Society, Washington, DC, 1994, p. 106. Y. Ju, D. Kumar, R.S. Varma, J. Org. Chem. 71 (2006) 6697. R.G.R. Bacon, in: N. Kharasch (Ed.), Organic Sulfur Compounds, Pergamon Press, New York, 1961, p. 304. J.W. Pavlik, P. Tongcharoensirikul, N.P. Bird, A.C. Day, J.A. Barltrop, J. Am. Chem. Soc. 116 (1994) 2292. T. Sasaki, A. Nakanishi, M. Ohno, J. Org. Chem. 469 (1981) 5445. Y. Tamura, T. Kawasaki, M. Adachi, M. Tanio, Y. Kita, Tetrahedron Lett. 18 (1977) 4417. N. Iranpoor, H. Firouzabadi, H. Shaterian, Synlett (2000) 65. P. Molina, M. Alajarin, A. Ferao, M.J. Lindon, P.M. Fresneda, M.J. Vilaplana, Synthesis (1982) 472. P.Y. Renard, H. Schwebel, P. Vayron, E. Leclerc, S. Diasa, C. Mioskowskia, Tetrahedron Lett. 42 (2001) 8479. R.G.R. Bacon, R.G. Guy, J. Chem. Soc. 2428 (1961) 2436. T. Takido, M. Toriyama, K. Yamashita, T. Suwa, M. Seno, Phosphorus, Sulfur, and Silicon 178 (2003) 319. Z.H. Weng, J.Y. Wang, X.G. Jian, Chin. Chem. Lett. 18 (2007) 936. M.J. O Donnell, Asymmetric Phase Transfer Reactions, in: I. Ojima (Ed.), Catalytic Asymmetric Synthesis, Verlag Chemie, New York, 2000. A.R. Kiasat, B. Mokhtari, A. Savari, F. Kazemi, Phosphorus, Sulfur, and Silicon 183 (2008) 178. S. Mallakpour, Z. Rafiee, Eur. Polym. J. 43 (2007) 1510. B.X. Tang, F. Wang, J.H. Li, Y.X. Xie, M.B. Zhang, J. Org. Chem. 72 (2007) 6294. N. Iranpoor, H. Firouzabadi, N. Nowrouzi, Tetrahedron 62 (2006) 5498.
Chinese Chemical Letters 19 (2008) 1301–1304 www.elsevier.com/locate/cclet
A facile and convenient method for synthesis of alkyl thiocyanates under homogeneous phase transfer catalyst conditions Ali Reza Kiasat *, Rashid Badri, Soheil Sayyahi Chemistry Department, College of Science, Shahid Chamran University, Ahvaz 61357-4-3169, Iran Received 15 May 2008
Abstract A simple and environmentally friendly method is described for the efficient conversion of alkyl halide to alkyl thiocyanate using tetrabutylammonium bromide (TBAB) as a phase transfer catalyst. The reactions occur in water and furnish the corresponding alkyl thiocyanate in high yields. No evidence for the formation of isothiocyanates as by-product of the reaction was observed and the products were obtained in pure form without further purification. # 2008 Ali Reza Kiasat. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Alkyl thiocyanate; Alkyl halide; Tetrabutylammonium bromide; Phase transfer catalyst; Synthesis of alkyl thiocyanates
It is well known that the alkyl thiocyanate [1] plays an important role as an intermediate for the preparation of sulfur-containing organic compounds [2]. They have found a wide variety of applications as insecticides, biocidal, antiasthmatic and starting materials for the preparation of heterocycles. Thiocyanates are also considered to be an important class of compounds found in some anticancer natural products formed by deglycosylation of glucosinolates derived from cruciferous vegetables [3]. Moreover, a-thiocyanatocarbonyl compounds are intermediates for a preferred synthetic route to several types of thiazoles [4]. Thiocyanation is generally carried out via nucleophilic substitution using thiocyanate anions. A number of methods are available for the preparation of alkyl thiocyanates, such as, displacement of leaving groups with thiocyanate ions [5–7]. Thiocyanates can also be obtained from alcohols [8], silyl ethers [9] or amines [10]. However, this displacement frequently requires rather severe reaction conditions because of the low nucleophilicity of the NCS ion. Hence many drawbacks and low yields have been observed for these thiocyanation methodologies [2,11]. In addition, the thiocyanate group is poorly stable when heated or under acidic conditions. Chromatography on silica gel or prolonged heating over 50 8C can cause intramolecular rearrangement to the thermodynamically favored isothiocyanate isomers [12]. Consequently, the development of new methods that are more efficient and lead to convenient procedures and better yields is desirable. Phase transfer catalysts (PTCs) are powerful reagents in chemical transformations [13,14], the characteristics of which include mild reaction conditions, safety, operational simplicity and selectivity. PTCs are often used in nucleophilic displacement reactions to facilitate reactions between organic reactants and ionic inorganic salts [15].
* Corresponding author. E-mail address: [email protected] (A.R. Kiasat). 1001-8417/$ – see front matter # 2008 Ali Reza Kiasat. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2008.07.019
1302
A.R. Kiasat et al. / Chinese Chemical Letters 19 (2008) 1301–1304
Scheme 1.
Although many phase transfer catalysts are known, quaternary salts formed from ammonia are practically important and used in many of organic reactions. In continuation of our investigations on new methodologies for the synthesis of organo-sulfur compounds [16], we report a novel and highly efficient protocol that allows the rapid synthesis of alkyl thiocyanates using TBAB as a phase transfer catalyst under mild and homogeneous condition (Scheme 1). Its high polarity and ability to solubilize both organic and inorganic compounds can result in enhanced reaction rates and can provide higher selectivity compared to conventional methods [17,18]. 1. Experimental All 1H and 13C NMR data were recorded on a Bruker Advanced DPX 400 MHz instrument spectrometer using Me4Si as the internal standard in CDCl3. IR spectra were recorded on a BOMEM MB-Series 1998 FT-IR spectrometer. The purity determination of the products and reaction monitoring were accomplished by TLC on silica gel polygram SILG/UV 254 plates. General procedure: In a typical procedure, a mixture of alkyl halide (1.0 mmol), TBAB (0.5 mmol), KSCN (1.5 mmol) and water (3.0 mL) was placed in a flask and stirred at room temperature or heated (40 8C) for the time specified in Table 1. On completion of the reaction, followed by TLC examination, the mixture allowed to be cold and extracted into ether (3 5 mL). The combined organic layer washed with cold water (3 10 mL), dried over sodium sulfate and filtered. The filtrate was subjected to a vacuum gave the desired product (75–95%). It did not require any column chromatography thus avoiding the possibility of rearrangement. All of the reactions reported here were clean as judged by TLC, FTIR and NMR analysis of the crude reaction mixture. 2. Results and discussions In a first set of experiments, a well-stirred solution of 4-bromo benzyl bromide (1.0 mmol) in H2O (3.0 mL) was treated with KSCN (1-2 mmol) at room temperature in the presence of tetrabutylammonium bromide (0.2– 0.5 mmol) as a phase transfer catalyst. The reaction was monitored by TLC. After some experiments, it was found that the use of 1.5 equiv of KSCN per alkyl halide in the presence of TBAB (0.5 equiv) in water were the best conditions and after stirring for 45 min at room temperature, the clean formation of a product with lower Rf value was observed. We examined the catalytic ability of TBAB for conversion of alkyl halides to alkyl thiocyanate with KSCN in water at room temperature. This catalyst acted very efficiently and it converts different alkyl halides to their corresponding alkyl thiocyanates in high isolated yields. The obtained results of the reaction are given in Table 1. It is noteworthy that no evidence for the formation of Isothiocyanates as by-product of the reaction was observed and the products were obtained in pure form without further purification. 13C resonance of the SCN and NCS groups at 111 and 145 ppm, respectively, are very characteristic for thiocyanate and isothiocyanate functionalities [19]. As shown in Table 1 (entries 7 and 8), this simple method can be efficiently used for preparation of a-thiocyanato carbonyl compounds. As expected the effects of reactant structure on the rate of Bimolecular nucleophilic substitution (SN2) reactions have appeared in entry 12 as no product was observed even 8 h of variously stirring. In conclusion, we have developed an optimized facile thiocyanation under phase transfer catalyst, which requires only a moderate reaction temperature in water. The advantages of present protocol, such as clean reaction profiles, short reaction times, simplicity in operation and the low cost of reagents make this new process an attractive alternative to current methodologies.
A.R. Kiasat et al. / Chinese Chemical Letters 19 (2008) 1301–1304
1303
Table 1 Conversion of alkyl halide to alkyl thiocyanate under PTC in H2O Entry
Alkyl halide
Product
Time (min)
Yielda,b(%)
1
60
85
2
60
80
3
30
90
4
45
85
5
45
80 c
6
45
90 c
7
45
80
8
60
80 c
9
45
80 c
10
180
75
11
30
95c,d
12
a b c d e
–
8e
The NMR and FTIR spectra of all synthesized alkylthiocyanates are in accord with the literature [2,4,11]. Isolated yields. The reaction was performed at 40 8C. GC analysis. 8 h.
–
1304
A.R. Kiasat et al. / Chinese Chemical Letters 19 (2008) 1301–1304
Acknowledgment Partial support for this work by Chamran University Research Council is gratefully acknowledged. References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19]
R.G. Guy, in: S. Patai (Ed.), The Chemistry of the Cyanates and Their Thio Derivatives, Wiley Interscience, New York, 1977, p. 819. O. Prakash, H. Kaur, H. Batra, N. Rani, S.P. Singh, R.M. Moriarty, J. Org. Chem. 66 (2001) 2019. F. Shahidi, in: C.J. Mussinan, M.E. Keelan (Eds.), Sulphur Compounds in Foods, American Chemical Society, Washington, DC, 1994, p. 106. Y. Ju, D. Kumar, R.S. Varma, J. Org. Chem. 71 (2006) 6697. R.G.R. Bacon, in: N. Kharasch (Ed.), Organic Sulfur Compounds, Pergamon Press, New York, 1961, p. 304. J.W. Pavlik, P. Tongcharoensirikul, N.P. Bird, A.C. Day, J.A. Barltrop, J. Am. Chem. Soc. 116 (1994) 2292. T. Sasaki, A. Nakanishi, M. Ohno, J. Org. Chem. 469 (1981) 5445. Y. Tamura, T. Kawasaki, M. Adachi, M. Tanio, Y. Kita, Tetrahedron Lett. 18 (1977) 4417. N. Iranpoor, H. Firouzabadi, H. Shaterian, Synlett (2000) 65. P. Molina, M. Alajarin, A. Ferao, M.J. Lindon, P.M. Fresneda, M.J. Vilaplana, Synthesis (1982) 472. P.Y. Renard, H. Schwebel, P. Vayron, E. Leclerc, S. Diasa, C. Mioskowskia, Tetrahedron Lett. 42 (2001) 8479. R.G.R. Bacon, R.G. Guy, J. Chem. Soc. 2428 (1961) 2436. T. Takido, M. Toriyama, K. Yamashita, T. Suwa, M. Seno, Phosphorus, Sulfur, and Silicon 178 (2003) 319. Z.H. Weng, J.Y. Wang, X.G. Jian, Chin. Chem. Lett. 18 (2007) 936. M.J. O Donnell, Asymmetric Phase Transfer Reactions, in: I. Ojima (Ed.), Catalytic Asymmetric Synthesis, Verlag Chemie, New York, 2000. A.R. Kiasat, B. Mokhtari, A. Savari, F. Kazemi, Phosphorus, Sulfur, and Silicon 183 (2008) 178. S. Mallakpour, Z. Rafiee, Eur. Polym. J. 43 (2007) 1510. B.X. Tang, F. Wang, J.H. Li, Y.X. Xie, M.B. Zhang, J. Org. Chem. 72 (2007) 6294. N. Iranpoor, H. Firouzabadi, N. Nowrouzi, Tetrahedron 62 (2006) 5498.