Amphiphilic organocatalyst for schotten-baumann-type tosylation of alcohols under organic solvent free condition

Article abstract of DOI:10.1021/ol900125y

A Tosylation of primary alcohol with tosyl chloride was performed effectively with an W-hexadecylimidazole catalyst in water containing K ₂CO₃ aggregation of the catalyst carrying a hydrophobic methylene chain worked as a substitute for organic solvent.

Full text of DOI:10.1021/ol900125y

ORGANIC
LETTERS
2009
Vol. 11, No. 8
1757-1759
Amphiphilic Organocatalyst for
Schotten-Baumann-Type Tosylation of
Alcohols under Organic Solvent Free
Condition
Keisuke Asano and Seijiro Matsubara*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Kyoutodaigaku-Katsura, Nishikyo, Kyoto 615-8510, Japan
matsubar@orgrxn.mbox.media.kyoto-u.ac.jp
Received February 9, 2009
ABSTRACT
A Tosylation of primary alcohol with tosyl chloride was performed effectively with an N-hexadecylimidazole catalyst in water containing K2CO3.
aggregation of the catalyst carrying a hydrophobic methylene chain worked as a substitute for organic solvent.
Tosylation has long been recognized as a method for
converting alcohols into reactive electrophiles.1 While treat-
ment of alcohols with tosyl chloride and amine in an organic
solvent is a conventional method to prepare the tosylates,
the Schotten-Baumann method,2 which is performed with
tosyl chloride and an inorganic base such as potassium
carbonate in an organic solvent3 or in a biphase system
consisting of water and organic solvent,4 has also been
developed. As the Schotten-Baumann reaction can avoid the
use of a stoichiometric amount of amine, the procedures have
been evaluated from the economical and environmental
superiority. Even though the method was well planned, it
still requires an organic solvent. Tanabe reported an organic
solvent-free Schotten-Baumann-type tosylation in water, but
it requires control of the pH of water and slow addition of
tosyl chloride to prevent hydrolysis of the chloride.5 The
procedure reported by Kazemi without water and organic
solvent seems to be attractive, but it should be performed
under harsh conditions to use inorganic bases without water.6
We supposed that use of N-alkylimidazole as a nucleophilic
catalyst with a hydrophobic group7 for Schotten-Baumann-
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2005, 7, 711–715. (b) Nakatsuji, H.; Morita, J.; Misaki, T.; Tanabe, Y.
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(6) (a) Kazemi, F.; Massah, A. R.; Javaherian, M. Tetrahedron 2007,
63, 5083–5087. (b) Fazaeli, R.; Tangestaninejad, S.; Aliyan, H. Can.
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Manabe, K.; Kobayashi, S. Chem. Commun. 2003, 574–575. (i) Gajewski,
J. J.; Jurayj, J.; Kimbrough, D. R.; Gande, M. E.; Ganem, B.; Carpenter,
B. K. J. Am. Chem. Soc. 1987, 109, 1170–1186. (j) Inoue, Y.; Araki, K.;
Shiraishi, S. Bull. Chem. Soc. Jpn. 1991, 64, 3079–3083. (k) Pellissier, H.
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VCH: Weinheim, 1989. (b) Kabalka, G. W.; Varma, M.; Varma, R. S. J.
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Chem. Ber. 1886, 21, 3218–3222.
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N. Bull. Chem. Soc. Jpn. 1995, 68, 297–300. (b) Yoshida, Y.; Sakakura,
Y.; Aso, N.; Okada, S.; Tanabe, Y. Tetrahedron 1999, 55, 2183–2192.
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10.1021/ol900125y CCC: $40.75
Published on Web 03/19/2009
2009 American Chemical Society

type tosylation might realize an organic solvent-free condi-
tion, because aggregation of the amphiphilic compound in
water will form a hydrophobic phase, which may work as a
substitute for an organic solvent.8,9 It will prevent tosyl
chloride and the product from undergoing hydrolysis.
As shown in Scheme 1, n-octanol (0.5 mmol) was treated
with tosyl chloride (0.75 mmol) and potassium carbonate
Table 1. Organic Solvent Free Schotten-Baumann-Type
Tosylation of Various Alcohols with N-Hexadecylimidazole as a
Catalyst
tosylates/%a
Scheme 1. Organic Solvent Free Schotten-Baumann-Type
entry
alkanols (ROH)
HCt C(CH2)9OH
C3H7Ct CCH2OH
HCt CCH2OH
CH2dCHCH2OH
CH2dCH(CH2)4OH
E-C2H5CHdCH(CH2)2OH
Z-C2H5CHdCH(CH2)2OH
CH3O(CH2)6OH
Tosylation of 1-Octanol with Amines as a Catalyst
1
90
79
70
44
83
56
56
61
66
54
73
34
80
50
75
21b
24c
2
3
4
5
6
7
8
9
C2H5O(CH2)5OH
C3H7O(CH2)4OH
CH3(Ph)CHCH2OH
Benzylalcohol
10
11
12
13
14
15
16
17
PhOH
3,5-Dimethylphenol
2,2,2-Trifluoroethanol
C6H13CH(OH)CH3
C5H11CH(OH)C2H5
a Isolated Yields. b Starting material recovered in 64%. c Starting material
recovered in 66%.
(0.5 mmol) in the presence of N-alkylimidazole (0.1 mmol)
and water (10 mmol) at 25 °C for 2 h. The length of the
alkyl chain on imidazole determined the efficiency of
the reaction. While N-methyl or -butylimidazole afforded the
corresponding tosylate in poor yield, N-hexadecylimidazole
gave the product in 82% yield. When the reaction was
examined with 5.0 mmol of water in the N-hexadecylimi-
dazole case, the yield of tosylate was improved from 82%
to 95%. In the absence of water, the yield of the tosyate
was decreased to 43%.
triple bond in the substrate did not disturb the reaction (Table
1, entries 1-3). In the case of hexenols, the position of C-C
double bond was significant for the reaction to proceed
efficiently (Table 1, entries 5-7). Phenols were also converted
into the corresponding tosylates (Table 1, entries 13, 14).
Conversions of secondary alcohols were not high (entries 16,
17). The low conversion of 3-hexenols (Table 1, entries 6,7)
into the corresponding tosylates compared to 5-hexenol (Table
1, entry 5) may be explained as follows: We suppose that
N-alkylimidazole molecules align along the interface between
water and organic compounds (Figure 1).7a,9,10 The imidazo-
Under this organic solvent-free condition, various n-alkanols
were converted into the corresponding tosylates. As shown in
Scheme 2, n-alkanols from C1 to C10 were examined. Among
Scheme 2. Organic Solvent Free Schotten-Baumann-Type
Tosylation of 1-Alkanols with N-Hexadecylimidazole as a
Catalyst
them, methanol, ethanol, and propanol gave unsatisfactory
results, as they are too soluble in water to be tosylated.
Reactions starting from alcohols other than n-alkanols were
also examined, as shown in Table 1. The existence of a C-C
Figure 1. Role of alkyl chain in the catalyst.
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Org. Lett., Vol. 11, No. 8, 2009

lium species, which are formed from p-tosyl chloride and
N-alkylimidazole, may also work as an efficient surfactant.
Alkoxide, which is also formed by inorganic base in water,
can also work as a surfactant. The N-alkylimidazole, imi-
dazolium, and alkoxide are aligned in close proximity and
react to give the tosylate efficiently. Thus the alignment of
alkoxide, which keeps the right orientation in the N-
alkylimidazolium phase, will lead to high conversion; the
bent carbon chain skeleton such as 3-hexenol was unfavor-
able for the reaction.
stirred for 4 h in an oil bath kept at 25 °C. The mixture was
then diluted with ethyl acetate and dried over anhydrous
magnesium sulfate. The organic solution was concentrated
in vacuo. After purification with silica gel column chroma-
tography using hexane/ethyl acetate (v/v ) 30/1) as an eluent,
12 g of 3a was isolated in 83% yield.
Thus, we showed a novel organic solvent-free Schotten-
Baumann-type tosylation of primary alcohols. In this method,
the reaction proceeds efficiently by using a combination of
N-alkylimidazole and water without any organic solvent. The
affinity of the substrate to the hydrophobic part of the catalyst
plays an important role, and the method could be extended
to a tosylation that accompanies a molecular recognition.
This organic solvent-free method was also perfomed on
preparative scale, as shown in Scheme 3: to a 100 mL glass-
Acknowledgment. This work was supported financially
by the Japanese Ministry of Education, Culture, Sports,
Science and Technology.
Scheme 3
.
Tosylation of 1-Octanol in Water with Semi-Large
Scale
Supporting Information Available: Experimental details
and spectral data of the compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL900125Y
(9) (a) Hayashi, Y.; Aratake, S.; Okano, T.; Takahashi, J.; Sumiya, T.;
Shoji, M. Angew. Chem., Int. Ed. 2006, 45, 5527–5529. (b) Mase, N.; Nakai,
Y.; Ohara, N.; Yoda, H.; Takebe, K.; Tanaka, F.; Barbas, C. F., III J. Am.
Chem. Soc. 2006, 128, 734–735.
vessel, 1-octanol (50 mmol, 6.5 g), N-hexadecylimidazole
(5.0 mmol, 1.5 g), p-toluenesulfonyl chloride (75 mmol,
14 g), potassium carbonate (50 mmol, 6.9 g) and water (500
mmol, 9 mL) were added one by one. The mixture was
(10) Narayan, S.; Muldoon, J.; Finn, M. G.; Fokin, V. V.; Kolb, H. C.;
Sharpless, K. B. Angew. Chem., Int. Ed. 2005, 44, 3275–3279.
Org. Lett., Vol. 11, No. 8, 2009
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