Synthesis of intra annularly linked benzotriazolophane

Article abstract of DOI:10.1081/SCC-120004260

Reduction of 1,3-dialkyl benzotriazolium salts was carried out using NaH/THF. The methodology was applied for the synthesis of benzotriazolophane 2, which was intra annularly linked by p-xylenyl dibromide to give novel cyclophane 6 and reduction of benzot

Full text of DOI:10.1081/SCC-120004260

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SYNTHESIS OF INTRA ANNULARLY LINKED
BENZOTRIAZOLOPHANE
Perumal Rajakumar a , Venghatragavan Murali a & Natarajan Kalaivasan a
a Department of Organic Chemistry , University of Madras , Guindy Campus, Chennai,
Tamilnadu, 600 025, India
Published online: 16 Aug 2006.
To cite this article: Perumal Rajakumar , Venghatragavan Murali & Natarajan Kalaivasan (2002) SYNTHESIS OF INTRA
ANNULARLY LINKED BENZOTRIAZOLOPHANE, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 32:11, 1685-1690, DOI: 10.1081/SCC-120004260
To link to this article: http://dx.doi.org/10.1081/SCC-120004260
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SYNTHETIC COMMUNICATIONS, 32(11), 1685–1690 (2002)
SYNTHESIS OF INTRA ANNULARLY
LINKED BENZOTRIAZOLOPHANE
*
Perumal Rajakumar, Venghatragavan Murali, and
Natarajan Kalaivasan
Department of Organic Chemistry,
University of Madras, Guindy Campus,
Chennai-600 025, Tamilnadu, India
ABSTRACT
Reduction of 1,3-dialkyl benzotriazolium salts was carried out
using NaH/THF. The methodology was applied for the synth-
esis of benzotriazolophane 2, which was intra annularly linked
by p-xylenyl dibromide to give novel cyclophane 6 and reduc-
tion of benzotriazolophane 7 gave cyclophane 8.
The vast majority of references in benzotriazole chemistry is to patents
and only a few reactions are clearly established. Though benzotriazole has
been used as an appendage in the cyclophane system as early as 1996,[1] the
new class of cyclophanes, called benzotriazolophanes, in which benzotria-
zole is a part of the cyclophane system, has been reported recently from our
laboratory.[2] The cyclophanes derived from benzotriazoles have more num-
bers of potential binding sites and hence in our studies related to the chemi-
cal modification on benzotriazolophane, we focus our attention on the
reduction of benzotriazolophane using various hydride sources as reducing
*Corresponding author.
1685
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1686
RAJAKUMAR, MURALI, AND KALAIVASAN
agents. The reduction studies were carried out with benzotriazolium salts
with a view to search suitable reducing agents to convert benzotriazolo-
phane 1 to the corresponding amine 2.
To study model reactions, 4 was obtained in 83% yield by sequentially
alkylating benzotriazole with benzyl bromide. Reaction of 4 with NaH in
THF under nitrogen afforded the amine 5 (42%). Reduction of 4 with
NaBH4 gave only 15% of the amine 5 and reduction of 4 with LiAlH4
gave 1-benzylbenzotriazole (80%). Though 4a has been reported earlier,[3]
only in 9% yield, in the current investigation 4a was obtained in 70% yield
by sequential alkylation. Reduction of the iodide salt 4a with NaH in THF
gave the amine 5a (40%) (Scheme 1). Photochemical studies on benzo-
triazolium ion by Mcllroy et al.[4] also support our investigation.
Finally, benzotriazolophane 1[2] was reduced with NaH in THF to
give amine 2 (30%). Reaction of 2 with p-xylenyl dibromide in CH3CN,
followed by treatment with 25% NaOH, afforded the intra annularly linked
cyclophane 6 (40%) (Scheme 2).
Similarly, reduction of the cyclophane 7[2] with NaH under identical
condition amino acid 8 was obtained in 20% yield (Scheme 3).
Synthesis of other intra annularly linked cyclophanes is under
investigation.
Scheme 1.

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INTRA ANNULARLY LINKED BENZOTRIAZOLOPHANE
1687
Scheme 2. (i) NaH/THF, 12 h; (ii) p-xylenyl dibromide, CH3CN, reflux, 24 h; (iii)
25% NaOH, 48 h.
Scheme 3.
EXPERIMENTAL SECTION
1
Melting points are uncorrected. H NMR, (400 MHz) and 13C NMR
(100.4 MHz) were recorded in CDCl3 or DMSO-d6. Chemical shifts are
expressed in ppm using TMS as internal standard. IR spectra were recorded
on a Shimdzu FTIR-8300. Mass spectra were recorded on Finnigan
MAT8430 by EI (NH 3) and FAB (Matrix-NBA). Dry acetonitrile was
freshly prepared prior to use. Neutral alumina was used for column.
General Procedure for 1-Alkylbenzotriazole
To a stirred solution of benzotriazole (84 mmol) in acetonitrile
(150 ml) and NaOH solution (15 ml, 25%) was added at once the alkylating
agent (100 mmol) in acetonitrile (15 ml). The reaction mixture was stirred for

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RAJAKUMAR, MURALI, AND KALAIVASAN
two days, evaporated in vacua and extracted with chloroform (4 ꢀ 50 ml),
washed with saturated sodium chloride solution (2 ꢀ 50 ml), dried (MgSO4),
evaporated to dryness and purified by recrystallisation.
1-Benzylbenzotriazole 3: 93%, m.p. 114–115ꢁC; Lit.[3] m.p. 115ꢁC.
1-Methylbenzotriazole 3a: 73%, m.p. 63–64ꢁC; Lit.[3] m.p. 64ꢁC.
General Procedure for 1,3-Dialkylbenzotriazolium Halide
To a solution 1-alkyl benzotriazole (22.3 mmol) in acetonitrile (100 ml)
was added the alkylating agent (23.0 mmol) and refluxed for 48 h. Evapora-
tion of CH3CN gave the quaternary salt, purified by recrystallisation.
1,3-Dibenzylbenzotriazolium bromide 4: Pale brown coloured solid
(CH2Cl2 : hexane 1 : 2), 83%, m.p. 177ꢁC; H NMR ꢀ 6.32 (s, 4H); 7.41–
1
7.55 (m, 10H); 7.98 (dd, 2H, J 3.30 Hz), 8.01 (dd, 2H, J 2.90 Hz); 13C NMR
ꢀ 54.6, 114.2, 128.8, 129.0, 129.1, 131.4, 132.7, 134.6; m/z 300.1 (Mþ-Br);
Elemental analysis calcd (%) for C20H18N3Br: C, 63.09; H, 4.73; N, 11.04.
Found: C, 62.93; H, 4.64; N, 10.87.
1,3-Dimethylbenzotriazolium iodide 4a: Yellow needles (dioxane :
ethanol, 1 : 1), 70%, m.p. 188ꢁC; Lit.[3] m.p. 188ꢁC.
Reduction of 1,3-Dibenzylbenzotriazolium Bromide with NaBH4
Reduction of 1,3-dibenzylbenzotriazolium bromide (0.5 g, 1.32 mmol)
with NaBH4 (0.05 g, 1.32 mmol) in EtOH (50 ml) followed by the usual
workup and elution with hexane : CH2Cl2 (1 : 1) gave 1-benzylbenzotriazole
(0.19 g, 70%) and further elution with hexane : CH2Cl2 (1 : 2) gave 1,3-diben-
zyl-[2H]benzotriazole (0.06 g, 15%) m.p. 101ꢁC; IR ꢁ (KBr): 3398; 1H NMR
ꢀ 5.76 (s, 4H); 7.18–7.34 (m, 12H); 7.99 (d, 2H, 7.28 Hz; 13C NMR ꢀ 52.5,
110.0, 120.3, 124.2, 127.8, 129.3, 133.1, 135.0; m/z 301(Mþ); Elemental
analysis calcd (%) for C20H19N3: C, 79.70; H, 6.35; N, 13.94. Found:
C, 79.24; H, 6.29; N, 13.54.
Reduction of 1,3-Dibenzylbenzotriazolium Bromide with LAH
Reduction of 1,3-dibenzylbenzotriazolium bromide (0.5 g, 1.32 mmol)
with LiAlH4 (0.047 g, 1.32 mmol) in THF (50 ml) followed by the usual
workup and elution with hexane : CH2Cl2 (1 : 1) gave 1-benzylbenzotriazole
(0.22 g, 80%).

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INTRA ANNULARLY LINKED BENZOTRIAZOLOPHANE
1689
General Procedure for the Reduction of 1,3-Dialkylbenzotriazolium
Salt with NaH
Reduction of the dialkyl benzotriazolium salt (7.24 mmol) with NaH
(7.24 mmol) in THF (100 ml) followed by the usual workup and purified by
column.
1,3-Dibenzyl-[2H]-benzotriazole 5: 0.92 g, 42%.
1
1,3-Dimethyl-[2H]-benzotriazole 5a: 0.43 g, 40%; H NMR ꢀ 4.24 (s,
6H); 7.20–7.46 (m, 2H), 7.96 (d, 2H, 8.36 Hz); 13C NMR ꢀ 30.9, 101.4,
109.1, 119.8, 123.9, 127.3; m/z 149(Mþ); Elemental analysis calcd (%) for
C8H11N3: C, 64.42; H, 7.38; N, 28.18. Found: C, 64.32; H, 7.37; N, 27.92.
General Procedure for the Reduction of Cyclophane 2&8
Cyclophane 1/7 (0.33 mmol/0.23 mmol) was reduced with NaH
(0.66 mmol) in THF (50 ml) following the earlier procedure.
Cyclophane 2: 0.074 g, 30%; 1H NMR ꢀ 4.67 (s, 2H); 5.79 (s, 8H); 7.17–
7.64 (m, 28H); 7.98 (d, 4H, J 7.44 Hz); 13C NMR ꢀ 51.9, 109.7, 120.1, 123.9,
125.9, 126.0, 126.3, 127.3, 127.4, 127.8, 128.1, 129.3, 130.3, 132.8, 133.9,
140.9, 141.2, 146.3; m/z 750(Mþ); Elemental analysis calcd (%) for
C52H42N6: C, 83.20; H, 5.60; N, 11.20. Found: C, 82.97; H, 5.43; N, 11.02.
1
Cyclophane 8: 0.055 g, 20%; IR ꢁ (KBr): 3423, 1718; H NMR ꢀ 5.74
(s, 8H), 7.19–7.38 (m, 26H), 7.98 (d, 4H, J 8.12 Hz); m/z 838(Mþ); Elemental
analysis calcd (%) for C54H42N6O4: C, 77.31; H, 5.05; N, 10.02. Found:
C, 77.24; H, 4.96; N, 9.88.
Intra Annularly Linked Cyclophane 6
A solution of the cyclophane 2 (0.26 g, 0.35 mmol) and p-xylenyl
dibromide (0.09 g, 0.35 mmol) in dry acetonitrile (200 ml) was refluxed for
24 h. The reaction mixture was cooled and added NaOH solution (5 ml,
25%) with stirring during 30 min and then stirred for 48 h. Evaporation of
CH3CN followed by extraction with CHCl3 (2 ꢀ 50 ml) and evaporated to
dryness. Elution with hexane : CHCl3 (1 : 7) gave 6 as pale yellow solid.
0.12 g, 40%; m.p. 152ꢁC; H NMR ꢀ 5.89 (s, 12H), 7.26 (s, 4H, xylenyl
1
protons), 7.34–7.68 (m, 28H), 8.08 (d, 4H, J 8.32 Hz); 13C NMR ꢀ 51.9,
109.7, 120.1, 124.1, 125.9, 126.3, 126.9, 127.5, 127.8, 128.1, 129.3, 132.8,
133.9, 140.9, 141.2, 146.3; m/z 852 (Mþ); Elemental analysis calcd (%) for
C60H48N6: C, 84.48; H, 5.67; N, 9.85. Found: C, 84.32; H, 5.45; N, 9.76.

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1690
RAJAKUMAR, MURALI, AND KALAIVASAN
ACKNOWLEDGEMENT
VM thanks CSIR, New Delhi, for financial assistance.
REFERENCES
1. Ballestend, P.; Elguero, J.; Claramund, R.M. Tetrahedron 1985, 41,
5955–5963.
2. Rajakumar, P.; Murali, V. Tetrahedron 2000, 56, 5999–6003.
3. Katritzky, A.R.; Rachwal, S.; Kaster, K.C.; Mahni, F.; Law, K.W.;
Rubio, O. J.C.S. Perkin Trans I 1987, 781–789.
4. Mcllroy, S.; Cramer, C.J.; Falvey, D.E. Organic Letters 2000, 5,
2447–2450.
Received in the Netherlands April 20, 2001