Poly(N-bromo-N-ethyl-benzene-1,3-disulfonamide), N,N,N′,N′- tetrabromobenzene-1, 3-disulfonamide as new efficient reagents for conversion of alcohols to THP ethers and aldehydes to oxazoline compounds

Article abstract of DOI:10.1007/BF03246014

This paper is concerned with an easy preparation of THP ethers from primary, secondary and tertiary alcohols and oxazoline compounds from various aldehydes using poly(N-bromo-N-ethyl-benzene-1,3-disulfonamide), N,N,N′,N′-tetrabromobenzene-1,3-disulfonamide [TBBDA] as new and efficient reagents under ambient conditions without over-oxidation.

Full text of DOI:10.1007/BF03246014

J. Iran. Chem. Soc., Vol. 7, No. 2, June 2010, pp. 301-307.
JOUIRrNaAnLiaOnF THE
Chemical Society
Poly(N -bromo-N-ethyl-benzene-1,3-disulfonamide), N,N,N',N'-Tetrabromobenzene-
1,3-disulfonamide as New Efficient Reagents for Conversion of Alcohols to THP Ethers
and Aldehydes to Oxazoline Compounds
R. Ghorbani-Vaghei*, S. Akbari-Dadamahaleh and M. Amiri
Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University,Hamedan, Iran
(Received 6 November 2008, Accepted 30 January 2009)
This paper is concerned with an easy preparation of THP ethers from primary, secondary and tertiary alcohols and oxazoline
compounds from various aldehydes using poly(N-bromo-N-ethyl-benzene-1,3-disulfonamide), N,N,N',N'-tetrabromobenzene-1,3-
disulfonamide [TBBDA] as new and efficient reagents under ambient conditions without over-oxidation.
Keywords: Oxazolines, THP ethers, Ambient conditions, TBBDA, PBBS
INTRODUCTION
[19], nitriles [20] hydroxy amides [21], aldehydes [22], and
olefins [23], have been reported previousely. The literature
survey, however, has revealed that there are only few methods
for the direct one-pot conversion of aldehydes to 2-substituted
oxazolines.
Recently, the N-bromosuccinimide and pyridinium
hydrobromide perbromide [24], have been reported for
oxidative conversion of aldehydes to corresponding 2-
substituted oxazolines. Although all of these methods afford 2-
oxazolines in good yields, some of them suffer from
drawbacks such as difficulty in multistep manipulation
[25,26], utilization of toxic reagents [27], high reactin
temperature (200-220 °C) [27c], higher stoichiometric use of
reagents [22,24], and stringent reaction parameters with
occasional low yields of the products.
The protection of hydroxyl groups is of paramount
importance in multi-step organic synthesis. THP ethers are the
most useful protective groups in multi-stage synthesis because
they are stable under neutral and basic conditions, and
resistant to oxidizing and reducing agents [1]. THP groups are
also the protective groups of choice in peptide, nucleotide,
carbohydrate, and steroid chemistry [2]. Several reagents have
been developed as catalysts for the formation of THP ethers
from alcohols and 3,4-dihydro-2H-pyran (DHP). These
include p-TsOH [3], Fe(ClO4)3 [4], La(NO3)3.6H2O [5],
CuSO4.5H2O [6], AlCl3.6H2O [7], CaCl2 [8], Al(HSO4)3 [9],
LiBF4 [10], In(OTf)3 [11], Nafion-H [12], heteropolyacids
[13], Lithium perchlorate-diethyl ether [14] and NBS [15].
2-Oxazolines have attracted considerable attention because
they are present in a wide variety of biologically active natural
products [16]. The substructural units of oxazoline heterocycle
exist in a variety of naturally-occurring iron chelators [17a],
cytotoxic cyclic peptides [17b] and antimitotic [17c] and
neuroprotective agents [17d]. Several methods for the
synthesis of 2-oxazolines from carboxylic acids [18], esters
EXPERIMENTAL
General Procedure for Protection of Alcohols Using
TBBDA and PBBS in the Presence of Solvents
To a magnetically stirred solution of benzyl alcohol (1
mmol) and DHP (1.1 mmol), N,N,N',N'-tetrabromobenzene-
1,3-disulfonamide TBBDA (0.1 g, 0.19 mmol) or PBBS [28]
(0.1 g) and CH2Cl2 was added, and the mixture was stirred
*Corresponding author. E-mail: rgvaghei@yahoo.com

Ghorbani-Vaghei et al.
until the complete disappearance of starting material (as
monitored by TLC). After the completion of the reaction,
reagents were removed by simple filtration. Evaporation of
the solvent under reduced pressure gave the almost pure THP
ethers. Further purification using column chromatography n-
hexane/acetone (9:2) gave the product as a liquid (Table 1).
Table 1. Tetrahydropyranylation of Various Alcohols Catalyzed by TBBDA and PBBS in CH
2Cl2 and Solvent-Free Conditions
at Room Temperature
Entry
Substrate
Product
TBBDA(CH2Cl2)
PBBS(CH2Cl2)
TBBDA(solvent-free)
PBBS(solvent-free)
Time (min) yield (%)a Time (min) yield (%)a
Time (min) yield (%)a Time (min) yield (%)a
OH
4
5
95
93
8
90
4
94
94
10
11
7
92
91
O
O
1
2
OH
Br
11
90
6
O
O
Br
OH
4
96
90
9
92
92
3
93
94
94
94
O
O
3
4
MeO
MeO
8
4
13
10
6
16
O
O
OH
OH
94
9
92
92
7
91
O
O
O
5
Cl
Cl
Cl
Cl
OH
Cl
6
93
92
10
19
93
90
6
93
91
9
90
O
Cl
6
7
OH
15
12
18
91
O
O
O
O
O
O
OH
20
5
93
25
94
18
94
25
92
O
8
Ph
Ph
Ph
Ph
92
92
85
13
13
28
92
94
82
5
95
12
17
22
93
91
88
CH2CH2OH
CH2CH2
O
O
9
10
10
13
15
94
90
OH
O
O
OH
Ph
O
O
11
12
18
Ph
OH
8
91
12
93
8
90
13
92
O
O
13
14
15
25
93
93
25
35
93
91
17
25
92
93
25
32
91
92
OH
OH
O
O
O
O
15
10
90
14
87
12
92
18
90
OH
O
O
O
16
20
91
30
85
17
92
24
90
OH
O
HO
O
O
aProducts were characterized by their physical properties, comparison with authentic samples, and by spectroscopic methods.
302

New Efficient Reagents for Conversion of Alcohols to THP Ethers and Aldehydes to Oxazolines
Table 2. Competitive Tetrahydropyranylation of Various Alcohols Catalyzed by TBBDA and
PBBS in the Presence of Solvent (CH2Cl2) at Room Temperature
Entry
1
Mixture
Product
Time (min)
5b or 15c
Conversion (%)a
80
OH
O
O
OH
OH
20
O
O
100
O
O
2
10b or 15c
20b or 30c
20b or 30c
OH
0
O
O
OH
OH
90
10
80
20
O
O
3
4
O
O
OH
OH
O
O
O
O
b
aThe conversion was detected by TLC and NMR spectroscopy. The conversion was
complied with TBBDA. cThe conversion was complied with PBBS.
mmol) and CH3CN (5 ml) or H2O (5 ml), TBBDA (0.15 g,
General Procedure for Solvent-Free Protection of
Alcohols Using TBBDA and PBBS
0.27 mmol) or PBBS (0.15 g) at room temperature, was added.
The mixture was stirred at room temperature for a period of
time specified in Table 4. After the completion of the reaction,
and evaporation of the solvent under reduced pressure, CH2Cl2
(10 ml) was added, and the reagents were removed by simple
filtration. Water (20 ml) and CH2Cl2 (25 ml) were added. The
organic layer was separated and dried (Na2SO4). Evaporation
of the solvent under reduced pressure gave the pure product
(92-98%).
Benzyl alcohol (1 mmol), DHP (2 mmol) was added to
N,N,N',N'-tetrabromobenzene-1,3-disulfonamide TBBDA (0.1
g, 0.19 mmol) or PBBS (0.1 g) at room temperature, and the
mixture was magnetically stirred until complete disappearance
of starting material (as monitored by TLC). After the
completion of the reaction, CH2Cl2 (5 ml) was added, and the
reagents were removed by simple filtration. Evaporation of the
solvent under reduced pressure gave the almost pure THP
ethers. Further purification using column chromatography n-
hexane/acetone (9:2) gave the product as a liquid (Table 1).
General Procedure for Solvent-Free Conversion of
Aldehydes to 2-Oxazoline Compounds Using TBBDA
and PBBS
To a mixture of substrate (1 mmol), ethanolamine (1.5
mmol) and TBBDA (0.15 g, 0.27 mmol) or PBBS (0.15 g) at
room temperature, was added. The mixture was stirred at room
General Procedure for Conversion of Aldehydes to 2-
Oxazoline Compounds Using TBBDA and PBBS in
the Presence of Solvents
To a mixture of substrate (1 mmol), ethanolamine (1.5
303

Ghorbani-Vaghei et al.
Table 3. Reaction Times and Yields of the Reaction of Alcohols with DHP Using Various Catalysts
Substrate
Conditions
Reaction time (h)
Yield (%)
p-Methoxybenzyl alcohol
p-Methoxybenzyl alcohol
p-Methoxybenzyl alcohol
Benzyl alcohol
La(NO3)3.6H2O
CuSO4.5H2O
NBS
La(NO3)3.6H2O
Lithium perchlorate in diethyl ether
2.5
0.66
3.5
2.5
12
955
896
7815
953
Benzyl alcohol
8614
Benzyl alcohol
Benzyl alcohol
Benzyl alcohol
Benzyl alcohol
Cyclohexanol
Cyclohexanol
Cyclohexanol
p-Chlorobenzyl alcohol
Benzhydrol
In(OTf)3, 0 ºC
CuSO4.5H2O
Ferric perchlorate
NBS
Lithium perchlorate in diethyl ether
In(OTf)3, 0 ºC
Ferric perchlorate
CuSO4.5H2O
0.5
0.66
1.5
2.5
12
0.5
2
0.75
9
8511
916
984
9515
8014
8511
944
926
9015
754
NBS
Ferric perchlorate
Benzhydrol
2.5
temperature for a period of time specified in Table 4. After the
completion of the reaction, CH2Cl2 (10 ml) was added to the
mixture and reagents were removed by simple filtration. Water
(20 ml) and CH2Cl2 (25 ml) were added. The organic layer was
separated and dried (Na2SO4). Evaporation of the solvent
under reduced pressure gave the pure product (87-98%).
Br
N
Br
N
Br
Br
Br
N
)
Br
N
S
S
S
S
O
O
CH2
CH2
)
n
O
O
O
O
O
O
TBBDA
PBBS
Scheme 1
RESULTS AND DISCUSSION
As part of our ongoing project to study the application of
poly(N-bromo-N-ethyl-benzene-1,3-disulfonamide) [PBBS]
DHP, TBBDA or PBBS
CH2Cl2, solvent-free, rt
O
R
O
R
OH
and
N,N,N',N'-tetrabromobenzene-1,3-disulfonamide
[TBBDA] [28-33] (Scheme 1), which is relatively easy to
make [28] in organic synthesis, we now report a mild and
efficient method for the conversion of alcohols to THP
compounds (Scheme 2). Various aromatic and aliphatic
alcohols were tetrahydropyranylated to THP compounds using
TBBDA or PBBS in good to high yields under ambient
conditions without any by-products.
Scheme 2
NH2CH2CH2OH
TBBDA or PBBS
N
O
R
CHO
R
CH3CN, H2O , solvent-free, rt
The results of oxidation of alcohols to THP ethers are
presented in Table 1. As shown in Table 1, primary, secondary
Scheme 3
304

New Efficient Reagents for Conversion of Alcohols to THP Ethers and Aldehydes to Oxazolines
305

Ghorbani-Vaghei et al.
and tertiary alcohols and phenols were all protected under the
[9] F. Shirini, M.A. Zolfigol, M. Abedini, Bull. Chem. Soc.
Jpn. 78 (2005) 1982.
[10] F. Kazemi, A.R. Kiasat, S. Ebrahimi, Synth. Commun.
32 (2002) 2483.
said conditions. We also found that sensitive compounds
(entries 7, 15), were protected under the above-mentioned
conditions without any by-products.
It was also found that N,N,N',N'-tetrabromobenzene-1,3-
disulfonamide [TBBDA] and poly(N-bromo-N-ethyl-benzene-
1,3-disulfonamide) [PBBS] were efficient reagents for the
conversion of aldehydes to oxazoline compounds (Scheme 3)
in the presence of 2-amino ethanol under (i) solvent-free, (ii)
solvent conditions.
[11] T. Mineno, Tetrahedron Lett. 43 (2002) 7975.
[12] G.A. Olah, A. Husain, B.P. Singh, Synthesis (1983) 892.
[13] G.P. Romanelli, G. Baronetti, H.J. Thomas, J.C. Autino,
Tetrahedron Lett. 43 (2002) 7589.
[14] B.S. Babu, K.K. Ralasubramanian, Tetrahedron Lett. 39
(1998) 9287.
Table 4 represents the treatment of a variety of aldehyds
with ethanol amine in the presence of solvent (CH3CN, H2O)
and solvent-free conditions using TBBDA or PBBS. It is
noteworthy that various aromatic aldehydes were converted to
oxazolines with high chemoselectivity without over-oxidation
of aldehydes to carboxylic acids. However, sevaral attempts to
convert aliphatic aldehydes to oxazolines using PBBS or
TBBDA under (i) solvent-free, (ii) solvent conditions failed.
[15] A. Khazaei, A. Rostami, A. Raiatzadeh, J. Chin. Chem.
Soc. 54 (2007) 1029.
[16] a) J.P. Genet, S. Thorimbert, A.M. Touzin, Tetrahedron
Lett. 34 (1993) 1159; b) P. Wipf, S. Venkatraman,
Synlett 1 (1997); c) Q. Li, K.W. Woods, A. Claiborne,
S.L. Gwaltney, K.J. Barr, G. Liu, L. Gehrke, R.B.
Credo, Y. Hua Hui, J. Lee, R.B. Warner, P. Kovar,
M.A. Nukkala, N.A. Zielinski, S.K. Tahir, M.
Fitzgerald, K.H. Kim, K. Marsh, D. Frost, S.C. Ng,
S.Rosenberg, H.L. Sham, Bioorg. Med. Chem. Lett. 12
(2002) 465; d) G. Compiani, M. de Angelis, S.
Armaroli, C. Fattorusso, B. Catalanotti, A. Ramunno, V.
Nacci, E. Novellino, C. Grewer, D. Ionescu, T. Rauen,
R. Griffiths, C. Sinclair, E. Fumagalli, T. Mennini, J.
Med. Chem. 44 (2001) 2507 .
ACKNOWLEDGMENTS
The authors gratefully acknowledge the financial support
of this research by the Center of Excellence and Development
of Chemical Methods (CEDCM), Bu-Ali Sina University.
REFERENCES
[17] a) H. Vorbrüggen, K. Krolikiewicz, Tetrahedron Lett. 39
(1993) 353; b) A. Cwik, Z. Hell, A. Hegedüs, Z. Finta,
Z. Horvath, Tetrahedron Lett. 43 (2002) 3985; c) B. P.
Bandgar, S.S. Pandit, Tetrahedron Lett. 44 (2003) 2331.
[18] a) D. Miller, G. Umbricht, B. Weber, A. Pfaltz, Helv.
Chim. Acta 74 (1991) 232; b) P. Zhou, J.E. Blubaum, C.
T. Burns, N.R. Natale, Tetrahedron Lett. 38 (1997)
7019.
[19] a) D.S. Clarke, R. Wood, Synth. Commun. 26 (1996)
1335; b) G.K. Jnaneshwara, V.H. Deshpande, M.
Lalithambika, T. Ravindranathan, A.V. Bedekar,
Tetrahedron Lett. 39 (1998) 7019.
[1] a) T.W. Green, P.G.M. Wuts, Protective Groups in
Organic Chemistry, John Wiley & Sons, New York,
(1991), b) P.J. Koconeshi, In Protecting Groups, Georg
Thame, New York, 1994.
[2] S. Hoyer, P. Laszlo, Synthesis (1986) 655.
[3] D.N. Robertson, J. Org. Chem. 25 (1960) 931.
[4] M.M. Heravi, F.K. Behbahani, H.A. Oskooie, R.H.
Shoar, Tetrahedron Lett. 46 (2005) 2543.
[5] T.S. Reddy, K.Ravinder, N. Suryakiran, M.
Narasimhulu, K.C. Mahesh, Y. Venkateswarlu,
Tetrahedron Lett. 47 (2006) 2341.
[6] T.K. Abu, H.C. Lokman, G. Subrata, Tetrahedron Lett.
45 (2004) 7891.
[20] a) E.J. Corey, K. Ishihara, Tetrahedron Lett. 33 (1992)
6807; b) P. Lafargue, P. Guenot, J.P. Lellouche,
Heterocycles 41 (1995) 947.
[7] V.N. Vasudevan, S.V. Rajender, Tetrahedron Lett. 43
(2002) 1143.
[8] Bandgar, B.P. Sadavarte, V.S. Uppalla, L.S. Patil, S.V.
Monatsh Chem. 134 (2003) 425.
[21] J.G. Badiang, J. Aube, J. Org. Chem. 61 (1996) 2484.
[22] S. Minakata, M. Nishimura, T. Takahashi, Y.
Oderaotoshi, M. Komatsu, Tetrahedron Lett. 42 (2001)
9019.
306

New Efficient Reagents for Conversion of Alcohols to THP Ethers and Aldehydes to Oxazolines
[23] K. Schwekendiek, F. Glorius, Synthesis (2006) 2996.
P. Wipf, C.P. Miller, Tetrahedron Lett. 33 (1992) 907.
[24] S. Sayama, Synlett (2006) 1479.
[28] R. Ghorbani-Vaghei, H. Jalili, Synthesis (2005) 1099.
[29] R. Ghorbani-Vaghei, M.A. Zolfigol, M. Chegeny, H.
Veisi, Tetrahedron Lett. 47 (2006) 4505.
[30] R. Ghorbani-Vaghei, E. Shahbazee, J. Braz. Chem. Soc.
16 (2005) 647.
[25] a) D.J. Neilson, in: S. Patai (Ed.), In The Chemistry of
Amidines and Imidates, Wiley, London, 1975, p. 389;
b) D. Hoppe, U. Schöllkopf, Angew. Chem., Int. Ed.
Engl. 9 (1970) 300.
[26] P.G.M. Wuts, J.M. Northuis, T.A. Kwan, J. Org. Chem.
65 (2000) 9223.
[31] M.A. Zolfigol, R. Ghorbani-Vaghei, S. Mallakpour, G.
Chehardoli, A. Ghorbani Choghamani, A. Hosain Yazdi,
Synthesis (2006) 1631.
[32] R. Ghorbani-Vaghei, E. Shahbazee, H. Veisi, Mendeleev
Commun. (2005) 207.
[33] R. Ghorbani-Vaghei, M. Amiri, N. Moshfeghifar, H.
Veisi, S. Akbari Dadamahaleh, J. Iran. Chem. Soc. 6
(2009) 754.
[27] a) Y. Hamada, M. Shibata, T. Shioiri, Tetrahedron Lett.
26 (1985) 6501; b) H. Wenker, J. Am. Chem. Soc. 57
(1935) 1079; c) M.E. Bunnage, A.N. Chernega, S.G.
Davies, C.J. Goodwin, J. Chem. Soc., Perkin Trans. l
(1994) 2385; d) A.J. Phillips, Y. Uto, P. Wipf, M.J.
Reno, D.R. Williams, Org. Lett. 2 (2000) 1165; e) P.
307