Easy and selective method for the synthesis of Mono-, di-, tri-, tetra-O-arylmethyl-p-t-butylcalix[4]arenes

Article abstract of DOI:10.3184/174751912X13371837407801

Mono-, di-, tri- and tetra-O-arylmethyl-p-t-butylcalix[4]arenes were synthesised respectively from p-t-butylcalix[4]arene and arylmethyl bromide through an easy and selective one-step reaction. Mono- and di-arylmethyl ethers of p-t-butylcalix[4]arenes wer

Full text of DOI:10.3184/174751912X13371837407801

402 RESEARCH PAPER
JULY, 402–406
JOURNAL OF CHEMICAL RESEARCH 2012
Easy and selective method for the synthesis of mono-, di-, tri-,
tetra-O-arylmethyl-p-t-butylcalix[4]arenes
Yuanyuan Xie* and Wang Xia
Key Laboratory for Green PharmaceuticalTechnologies and Related Equipment of Ministry of Education, College of Pharmaceutical
Sciences, Zhejiang University ofTechnology, Hangzhou 310014, P. R. China
Mono-,di-,tri-andtetra-O-arylmethyl-p-t-butylcalix[4]arenesweresynthesisedrespectivelyfromp-t-butylcalix[4]arene
and arylmethyl bromide through an easy and selective one-step reaction. Mono- and di-arylmethyl ethers of
p-t-butylcalix[4]arenes were prepared using LiH as a base, while tri- and tetra-arylmethyl derivatives were afforded
in the presence of Ba(OH)2 and BaO. These methods are remarkable for excellent selectivity, mild reaction conditions,
moderate to good yields and easy purification.
Keywords: p-t-butylcalix[4]arene, arylmethyl bromide, arylmethylation, recrystallisation
Calixarenes, which are cyclic oligomers of phenol-formalde-
hyde condensed compounds, are not planar and possess an
inner cavity.1–3 They are easily modified at the lower-rim4–6 or
upper-rim7–9 and the derivatives have attracted considerable
attention in many research areas, such as molecular recogni-
tion,10 enzyme mimics,11 phase transfer catalysis12 and com-
plex extraction.13 Generally, the starting materials for a variety
of these calixarene derivatives are p-t-butylcalix[4]arenes. The
p-t-butylcalix[4]arenes are a major class of organic macrocy-
clic compounds and have become common place in the field of
macrocyclic and supramolecular chemistry. With the constant
increase in the need for novel supramolecular hosts based
on these macrocycles, many chemists have been devoted to
developing new synthetic methods for their selective function-
alisation.
repeated in toluene using LiH as the base, only the mono-O-
arylmethyl-p-t-butylcalix[4]arene (3a) was obtained. Further
investigation proved that when compound 1 reacted with
arylmethyl bromides (2) in toluene using LiH as the base (the
molar ratio of 1:2:LiH = 1:1.5:1.5) at 70 °C for 8 h, the corre-
sponding mono-O-arylmethyl-p-t-butylcalix[4]arenes (3a–c)
were obtained in 67–72% yield (Table 1). It should be noted
that the products could be conveniently afforded with high
purity after simple recrystallisation.
Synthesis of di-O-arylmethyl-p-t-butylcalix[4]arenes
The reaction of compound 1 and arylmethyl halides in the
presence of K2CO3 in acetone proceeded under reflux for 24 h,
yielding di-O-arylmethyl-p-t-butylcalix[4]arenes.18–20 We found
that acetone can be substituted by DMF when LiH was used
instead of K2CO3. Interestingly, under these reaction condi-
tions (LiH as a base in DMF), only the di-O-arylmethylated
derivative was obtained. We further investigated the reaction
conditions of the single-step reaction between compound 1
and benzyl bromide using DMF as the solvent in the presence
of LiH. The results were summarised in Table 2. As can be
seen from Table 2, an optimal reaction condition was found
when compound 1 reacted with compound 2 in the presence of
LiH (the molar ratio of compound 1:compound 2:LiH = 1:4:4)
at 25 °C for only 6h (Table 2, entry 3), whereas the reaction
reported in the literature18 needed a longer time, and an excess
of benzyl bromide and K2CO3 (the molar ratio of 1:benzyl
bromide:K2CO3 = 1:8:8). The reaction stopped at the di-O-
arylmethylated stage even with a large excess of compound 2
and LiH (Table 2, entries 4–6).
We now report the selective arylmethylation of p-t-
butylcalix[4]arenes to prepare the mono-, di-, tri- and tetra-
O-arylmethyl-p-t-butylcalix[4]arenes through a new efficient
one-step procedure (Scheme 1). All the products were purified
1
easily by recrystallisation and identified by H NMR, 13C
NMR, IR and MS as well as compared with data available in
the literature.
Results and discussion
Synthesis of mono-O-arylmethyl-p-t-butylcalix[4]arenes
According to the literature, mono-O-arylmethyl-p-t-butylcalix-
[4]arenes can be synthesised through a multi-step procedure14,15
or a one-step process from p-t-butylcalix[4]arene (1) using an
excess of the alkylating agent and NaOCH3,3 Ba(OH)2,16 K2CO3
or CsF17 as the base. Preliminary study showed that compound
1 reacted with benzyl bromide in the presence of Ba(OH)2
in DMF to produce a mixture of mono-, di- and tri-O-aryl-
methyl-p-t-butylcalix[4]arenes. It is rather difficult to stop the
O-arylmethylation reaction at the stage of mono-O-arylmethyl-
p-t-butylcalix[4]arene. However, when the reaction was
Synthesis of tri-O-arylmethyl-p-t-butylcalix[4]arenes
Gutsche et al.18 described a two-step synthesis of the tri-O-
benzyl-p-t-butylcalix[4]arene from compound 1. Hosseini
et al.21 reported that the reaction of compound 1 and a large
Scheme 1 Synthesis of O-arylmethyl-p-t-butylcalix[4]arenes.
* Correspondent. E-mail: pharmlab@zjut.edu.cn

JOURNAL OF CHEMICAL RESEARCH 2012 403
Table 1 Synthesis of O-arylmethyl-p-t-butylcalix[4]arenes
Entry
R2
R3
R4
R5
Products
Yield/%a
1
2
C6H5CH2
H
H
H
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
70
67
72
79
76
81
82
80
85
83
80
87
79
81
82
83
85
86
4-IC6H4CH2
4-CH3C6H4CH2
C6H5CH2
H
H
H
3
H
H
H
4
H
C6H5CH2
4-IC6H4CH2
4-CH3C6H4CH2
C6H5CH2
4-IC6H4CH2
4-CH3C6H4CH2
C6H5CH2
4-IC6H4CH2
4-CH3C6H4CH2
4-IC6H4CH2
C6H5CH2
C6H5CH2
4-CH3C6H4CH2
C6H5CH2
C6H5CH2
H
5
4-IC6H4CH2
4-CH3C6H4CH2
C6H5CH2
4-IC6H4CH2
4-CH3C6H4CH2
C6H5CH2
H
H
6
H
H
7
C6H5CH2
4-IC6H4CH2
4-CH3C6H4CH2
C6H5CH2
4-IC6H4CH2
4-CH3C6H4CH2
4-IC6H4CH2
4-IC6H4CH2
C6H5CH2
4-CH3C6H4CH2
4-CH3C6H4CH2
C6H5CH2
H
8
H
9
H
10
11
12
13
14
15
16
17
18
C6H5CH2
4-IC6H4CH2
4-CH3C6H4CH2
4-IC6H4CH2
4-IC6H4CH2
4-IC6H4CH2
4-CH3C6H4CH2
4-CH3C6H4CH2
4-CH3C6H4CH2
4-IC6H4CH2
4-CH3C6H4CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
a Isolated yields based on p-t-butylcalix[4]arenes from recrystallisation in chloroform/methanol.
chloroform/methanol. When the molar ratio of compound 1,
Ba(OH)2 and BaO was 1:1.25:1.25, the reaction stopped at the
tri-O-arylmethylated stage even in the presence of excess
benzyl bromide (Table 3, entries 8 and 9).
Surprisingly, tetra-O-arylmethylated product 3j was found
when the reaction was carried out in the presence of slight
excess of Ba(OH)2 and BaO (Table 3, entry 5). Thus Ba(OH)2
and BaO were selected to synthesise the tetra-O-arylmethyl-p-
t-butylcalix[4]arenes, which will be described in the following
paragraph.
Table 2 Optimisation of reaction conditions of product 3d
Entry
Molar ratioa
Time/h
Yield/%b
1
2
3
4
5
6
1:2:4
1:3:4
1:4:4
1:4:8
1:8:8
1:8:16
12
12
6
39
60
79
79
75
77
6
6
6
a Molar ratio is compound 1:benzyl bromide:LiH.
b Isolated yields based on compound 1.
Synthesis of tetra-O-arylmethyl-p-t-butylcalix[4]arenes
The typical base used for synthesis of tetra-O-arylmethylation
of p-t-butylcalix[4]arenes is NaH.18 As described above, we
found that tetra-O-arylmethylated product 3j was produced
easily in the presence of excess Ba(OH)2 and BaO. To the best
of our knowledge, preparation of the tetra-O-arylmethyl-p-t-
butylcalix[4]arenes using Ba(OH)2 and BaO as the base has
not been reported. Therefore, we investigated the one-step
reaction of compound 1 and benzyl bromide at 25 °C using
DMF as the solvent in the presence of Ba(OH)2 and BaO
and the results are presented in Table 3 (entries 10–14). The
optimal molar ratio of compound 1, benzyl bromide, Ba(OH)2
and BaO is 1:5:2.5:2.5. The product 3j was obtained in 83%
yield, whereas only 63% yield was reported18 using much
larger excess of benzyl bromide and NaH (the molar ratio of 1:
arylmethyl bromide:NaH = 1:8:8).
excess of benzyl chloride in MeCN in the presence of excess
Ba(OH)2 and BaO (the molar ratio of compound 1:benzyl
chloride:Ba(OH)2:BaO = 1:20:6.5:7) afforded tri-O-benzyl-p-
t-butylcalix[4]arenes in 63% yield. In order to find a one-step
synthetic method which reduces the amount of arylmethyl
reagent, we investigated the reaction of compound 1 and
benzyl bromide using CHCl3, THF or DMF as the solvent in
the presence of Ba(OH)2 and BaO. It was found that DMF was
the optimal one among the tested solvents. The reaction of
compound 1 and benzyl bromide in the presence of Ba(OH)2
and BaO (the molar ratio of compound 1:benzyl bromide:
Ba(OH)2:BaO = 1:3:1.25:1.25) was carried out at 25 °C in
DMF, selectively yielding the tri-O-arylmethylated product
3g (Table 3, entry 6). The reaction was completed in 2.5 h
and the product was obtained easily by recrystallisation in
Table 3 Optimisation of reaction conditions of product 3g and 3j
Entry
Molar ratioa
Solvent
Temp/°C
Time/h
Product
Yield/%b
1
2
1:3:1.5:1.5
1:3:1.5:1.5
1:3:1.5:1.5
1:3:1.25:1.25
1:3:1.5:1.5
1:3:1.25:1.25
1:3:1:1
CHCl3
CHCl3
THF
25
Reflux
25
12
12
6
3g
3g
3g
3g
3g
3g
3g
3g
3g
3j
Trace
<10
35
3
4
THF
25
6
55
5
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
25
3
62c
82
6
25
2.5
3
7
25
57
8
1:4:1.25:1.25
1:6:1.25:1.25
1:4:2:2
25
3
79
9
25
3
78
10
11
12
13
14
25
3
72
1:5:2:2
25
3
3j
75
1:4.5:2.5:2.5
1:5:2.5:2.5
1:10:5:5
25
3
3j
80
25
3
3j
83
25
3
3j
82
a Molar ratio is compound 1:benzyl bromide:Ba(OH)2:BaO.
b Isolated yields based on compound 1.
c A small amount of tetra-O-arylmethyl-p-t-butylcalix[4]arene 3j was obtained.

404 JOURNAL OF CHEMICAL RESEARCH 2012
Scheme 2 Synthesis of tetra-O-arylmethyl-p-t-butylcalix[4]arenes with two different arylmethyl groups.
Synthesis of tetra-O-arylmethyl-p-t-butylcalix[4]arenes with two
Experimental
different arylmethyl groups
Melting points were obtained on a Buchi B-540 apparatus and are
uncorrected. IR spectra were recorded in KBr using Nicolet Avatar-
370 spectrophotometer. 1H NMR and 13C NMR spectra were recorded
for CDCl3 solutions using Varian Mercury Plus-400 instrument at 400
and 100 MHz, respectively. ESI-MS spectra were recorded on Thermo
Finnigan LCQ Advantage instrument. HRMS spectra were recorded
on Agilent 6210 TOF instrument.
We first tried to synthesise this hybrid arylmethylated tetramer
using Ba(OH)2 and BaO as the base. However, all attempts
failed. Kleij et al.20 reported the synthesis of 25-(4-iodobenzyl-
oxy)-26,27,28-tribenzyloxy-p-t-butylcalix[4]arene in the
presence of NaH at room temperature for 64 h. On the basis
of this result, we attempted to use NaH for this purpose. The
partially arylmethylated p-t-butylcalix[4]arene derivatives
(such as 3a, 3d and 3g) were chosen as the starting material
and arylmethyl bromide as the electrophile reagent. The
reaction of compound 3a and compound 2b proceeded
smoothly in THF and DMF (9:1) in the presence of NaH at
70 °C, yielding product 3m. The study was then extended
to di- or tri-O-benzyl-p-t-butylcalix[4]arene using the same
arylmethylating reagents 2b, and the tetra-O-arylmethylated
derivatives were afforded in good yields (Table 1, entries 14
and 15). The reaction was completed in 2 h whereas the
reaction in the literature20 yielding the tetra-O-arylmethylated
derivative 3o took 64 h. Treatment of mono-, di- or tri-O-
benzyl-p-t-butylcalix[4]arenes with compound 2c in the pres-
ence of NaH gave products 3p, 3q and 3r in excellent yields
(Table 1, entries 16–18).
In conclusion, a facile and efficient approach to the selective
synthesis of mono-, di-, tri- and tetra-O-arylmethyl-p-t-butyl-
calix[4]arenes was developed. Through regioselective aryl-
methylation of p-t-butylcalix[4]arenes with a little excess of
arylmethyl bromide, the desired products could be obtained
in good to excellent yields. The 4-methylbenzyl bromide
showed slightly higher yields than the 4-iodobenzyl bromide.
The products were purified easily by recrystallisation in
chloroform/methanol. The one-step procedure showed high
selectivity and may have broad applications in the synthesis
of mono-, di-, tri- and tetra-O-arylmethyl-p-t-butylcalix[4]-
arenes.
Synthesis of mono-O-arylmethyl-p-t-butylcalix[4]arenes 3a–c;
general procedure
A mixture of compound 1 (1.296 g, 2 mmol), LiH (0.024 g, 3 mmol)
and compound 2 (3 mmol) in toluene (50 mL) was heated at 70 °C for
8 h under a N2 atmosphere. After cooling, the reaction was quenched
with a few drops of methanol, and the solvent was removed under
vacuum. The residue was mixed with water and extracted with dichlo-
romethane (3×15 mL), andthe combined organic layers were dried
over anhydrous Na2SO4. The solution was filtered, concentrated and
recrystallised from chloroform/methanol to yield the corresponding
mono-O-arylmethyl-p-t-butylcalix[4]arenes 3a–c.
25-Benzyloxy-26,27,28-trihydroxy-p-t-butylcalix[4]arene (3a): White
needles; m.p. 223.1–225.0 °C; [lit.16 219–220 °C]; IR vmax = 3334,
l
3051, 2958, 2869, 1484, 1362, 1205, 870, 783, 696 cm−1; H NMR
(CDCl3) δ 9.98 (s, 1H, OH), 9.36 (s, 2H, OH), 7.69 (d, J = 8.0 Hz, 2H,
ArH), 7.50– 7.42 (m, 3H, ArH), 7.09 (s, 2H, ArH), 7.02 (d, J = 2.4 Hz,
2H, ArH), 7.00 (s, 2H, ArH), 6.94 (d, J = 2.0 Hz, 2H, ArH), 5.15
(s, 2H, OCH2Ph), 4.32 (d, J = 12.8 Hz, 2H, ArCH2Ar), 4.20 (d,
J = 13.6 Hz, 2H, ArCH2Ar), 3.39 (dd, J1 = 12.8 Hz, J2 = 2.0 Hz, 4H,
ArCH2Ar), 1.20 (s, 27H, C(CH3)3), 1.19 (s, 9H, C(CH3)3); 13C NMR
(CDCl3) δ 149.2, 148.3, 148.1, 147. 6, 143.4, 142.9, 135.5, 133.5,
129.0, 128.9, 128.8, 128.2, 127.9, 127.5, 126.4, 125.6, 125.5,
79.2, 34.4, 34.1, 34.0, 33.1, 32.6, 31.6, 31.4; MS(ESI): m/z (%) =
737(M− – 1, 100).
25-(4-Iodobenzyloxy)-26,27,28-trihydroxy-p-t-butylcalix[4]arene
(3b): White needles; m.p. 167.5–170.1 °C; [lit.20 141–142 °C]; IR vmax
= 3320, 3051, 2960, 2868, 1485, 1362, 1204, 869, 782 cm−1; lH NMR
(CDCl3) δ 9.93 (s, 1H, OH), 9.29 (s, 2H, OH), 7.82 (d, J = 8.0 Hz, 2H,
ArH), 7.46 (d, J = 8.0 Hz, 2H, ArH), 7.08 (s, 2H, ArH), 7.02 (s, 2H,

JOURNAL OF CHEMICAL RESEARCH 2012 405
ArH), 7.00 (s, 2H, ArH), 6.95 (s, 2H, ArH), 5.07 (s, 2H, OCH2Ar),
4.28 (d, J = 12.8Hz, 2H,ArCH2Ar), 4.20 (d, J = 13.6Hz, 2H,ArCH2Ar),
3.40 (d, J = 13.2Hz, 4H, ArCH2Ar), 1.19 (s, 36H, C(CH3)3); 13C NMR
(CDCl3) δ 148.6, 147.9, 147.1, 143.1, 142.6, 137.6, 134.8, 133.0,
130.4, 127.8, 127.4, 127.1, 126.2, 125.4, 125.3, 125.2, 94.6, 78.0,
34.1, 33.8, 33.7, 32.8, 32.2, 31.3, 31.1; MS(ESI): m/z (%) = 882
(M+ + NH4, 100).
δ 7.45 (d, J = 6.8 Hz, 2H, ArH), 7.27–7.18 (m, 13H, ArH), 7.06 (s,
2H, ArH), 6.97 (s, 2H, ArH), 6.56 (d, J = 2.4 Hz, 2H, ArH), 6.49 (d,
J = 2.4 Hz, 2H, ArH), 6.32 (s, 1H, OH), 4.92 (s, 2H, OCH2Ar), 4.65
(d, J = 11.6 Hz, 2H, OCH2Ar), 4.58 (d, J = 11.6 Hz, 2H, OCH2Ar),
4.17 (d, J = 13.6 Hz, 2H, ArCH2Ar), 4.13 (d, J = 12.8 Hz, 2H,
ArCH2Ar), 3.03 (d, J = 13.2Hz, 2H, ArCH2Ar), 2.96 (d, J = 12.8 Hz,
2H, ArCH2Ar), 1.31 (s, 9H, C(CH3)3), 1.29 (s, 9H, C(CH3)3), 0.83 (s,
18H, C(CH3)3); 13C NMR (CDCl3) δ 153.1, 150.8, 150.7, 145.4, 145.2,
140.9, 138.3, 137.3, 135.6, 132.4, 132.1, 129.2, 128.6, 128.5, 128.0,
127.6, 127.4, 127.0, 125.3, 124.8, 77.5, 76.0, 34.2, 33.9, 33.8, 31.84,
31.79, 31.7, 31.4, 31.1; MS(ESI): m/z (%) = 827(100), 917 (M− – 1,
70).
25-(4-Methylbenzyloxy)-26,27,28-trihydroxy-p-t-butylcalix[4]-
arene (3c): White needles; m.p. 129.2–131.0 °C; IR vmax = 3332, 3049,
1
2960, 2868, 1484, 1362, 871, 783 cm−1; H NMR (CDCl3) δ 10.00
(s, 1H, OH), 9.39 (s, 2H, OH), 7.58 (d, J = 8.0 Hz, 2H, ArH), 7.28 (d,
J = 7.6 Hz, 2H, ArH), 7.10 (s, 2H, ArH), 7.03 (d, J = 2.4 Hz, 2H, ArH),
7.01 (s, 2H,ArH), 6.95 (d, J = 2.0 Hz, 2H,ArH), 5.13 (s, 2H, OCH2Ar),
4.33 (d, J = 12.8 Hz, 2H, ArCH2Ar), 4.22 (d, J = 13.6 Hz, 2H,
ArCH2Ar), 3.39 (d, J = 13.2 Hz, 4H, ArCH2Ar), 2.42 (s, 3H, CH3),
1.22 (s, 18H, C(CH3)3), 1.21 (s, 18H, C(CH3)3); 13C NMR (CDCl3)
δ 149.2, 148.3, 148.0, 147.6, 143.3, 142.8, 138.6, 133.5, 132.5, 129.4,
129.1, 128.1, 127.9, 127.5, 126.3, 125.5, 125.4, 79.1, 34.4, 34.1, 34.0,
33.1, 32.6, 31.6, 31.4, 21.5; MS(ESI): m/z (%) = 751 (M− – 1, 100);
HRMS-ESI: Calcd for C52H68NO4 (M+NH4)+: 770.5148; found:
770.5113.
25,26,27-Tris(4-iodobenzyloxy)-28-hydroxy-p-t-butylcalix[4]arene
(3h): White solid; m.p. 217.2–219.1 °C; IR vmax = 3446, 3042, 2959,
l
2866, 1483, 1197, 870, 801 cm−1; H NMR (CDCl3) δ 7.54 (d, J =
8.4 Hz, 6H, ArH), 7.36 (d, J = 8.0 Hz, 2H, ArH), 7.12 (s, 2H, ArH),
7.00 (s, 2H, ArH), 6.87 (d, J = 8.4 Hz, 4H, ArH), 6.57 (d, J = 2.4 Hz,
2H, ArH), 6.48 (d, J = 2.4 Hz, 2H, ArH), 6.22 (s, 1H, OH), 4.76 (s, 2H,
OCH2Ar), 4.53 (d, J = 11.6 Hz, 2H, OCH2Ar), 4.43 (d, J = 11.6 Hz,
2H, OCH2Ar), 4.10 (d, J = 4.0 Hz, 2H, ArCH2Ar), 4.07 (d, J = 4.8 Hz,
2H, ArCH2Ar), 3.08 (d, J = 13.2 Hz, 2H, ArCH2Ar), 3.03 (d, J =
12.4 Hz, 2H, ArCH2Ar); 1.33 (s, 9H, C(CH3)3), 1.30 (s, 9H, C(CH3)3),
0.82 (s, 18H, C(CH3)3); 13C NMR (CDCl3) δ 152.6, 150.1, 145.7,
145.2, 140.8, 137.4, 136.9, 136.1, 136.0, 135.1, 131.8, 131.6, 130.4,
129.9, 127.8, 125.2, 124.6, 124.5, 93.5, 92.4, 76.8, 74.9, 33.9, 33.6,
33.5, 31.52, 31.46, 31.3, 30.8; MS(ESI): m/z (%) = 1314 (M+ + NH4,
100); HRMS-ESI: Calcd for C65H75I3NO4 (M+NH4)+: 1314.2830;
found: 1314.2782.
25,26,27-Tris(4-methylbenzyloxy)-28-hydroxy-p-t-butylcalix[4]-
arene (3i): White needles; m.p. 184.2–186.1 °C; IR vmax = 3414, 3044,
2948, 2865, 1480, 1198, 870, 802 cm−1; 1H NMR (CDCl3) δ 7.35 (d,
J = 8.0 Hz, 2H, ArH), 7.14 (d, J = 8.0 Hz, 4H, ArH), 7.05(s, 2H, ArH),
7.04 (d, J = 7.6 Hz, 4H, ArH), 6.99 (d, J = 8.0 Hz, 2H, ArH), 6.96 (s,
2H, ArH), 6.55 (d, J = 2.4 Hz, 2H, ArH), 6.48 (d, J = 2.4 Hz, 2H,
ArH), 6.34 (s, 1H, OH), 4.89 (s, 2H, OCH2Ar), 4.60 (d, J = 11.6 Hz,
2H, OCH2Ar), 4.55 (d, J = 11.2 Hz, 2H, OCH2Ar), 4.16 (d, J = 1.2 Hz,
2H, ArCH2Ar), 4.13 (d, J = 2.0 Hz, 2H, ArCH2Ar), 3.01 (d, J =
13.2 Hz, 2H, ArCH2Ar), 2.97 (d, J = 12.8 Hz, 2H, ArCH2Ar), 2.33 (s,
3H, CH3), 2.32 (s, 6H, CH3), 1.31 (s, 9H, C(CH3)3), 1.28(s, 9H,
C(CH3)3), 0.83 (s, 18H, C(CH3)3); 13C NMR (CDCl3) δ 153.2, 150.9,
150.7, 145.2, 145.0, 140.8, 137.1, 136.2, 135.6, 135.4, 134.4, 132.4,
132.1, 129.2, 128.7, 128.1, 125.3, 124.7, 77.4, 75.8, 34.2, 33.9, 33.8,
31.9, 31.8, 31.5, 31.2, 21.4; MS(ESI): m/z (%) = 983 (M+ + Na, 100);
HRMS-ESI: Calcd for C68H84NO4 (M+NH4)+: 978.6400; found:
978.6405.
Synthesis of di-O-arylmethyl-p-t-butylcalix[4]arenes 3d–f; general
procedure
A mixture of compound 1 (1.296 g, 2 mmol), LiH (0.064 g, 8 mmol)
and compound 2 (8 mmol) was stirred at 25 °C in DMF (60 mL) for
6 h under a N2 atmosphere. A few drops of methanol were added and
the reaction mixture was concentrated in vacuo. Water (100 mL) was
added to the residue and the crude product was precipitated. Recryst-
allisation from chloroform/methanol afforded the corresponding
di-O-arylmethyl-p-t-butylcalix[4]arenes 3d–f.
25,27-Bis(benzyloxy)-26,28-dihydroxy-p-t-butylcalix[4]arene (3d):
White needles; m.p. 234.3–236.8 °C; [lit.18 239–241 °C]; IR vmax
=
3395, 3285, 2958, 2866, 1484, 1362, 1205, 871, 781 cm−1; H NMR
(CDCl3) δ 7.64–7.61 (m, 4H, ArH), 7.35–7.33 (m, 6H, ArH), 7.28 (s,
2H, OH), 7.02 (s, 4H, ArH), 6.77 (s, 4H, ArH), 5.04 (s, 4H, OCH2Ar),
4.27 (d, J = 12.8 Hz, 4H, ArCH2Ar), 3.26 (d, J = 13.2 Hz, 4H,
ArCH2Ar), 1.28 (s, 18H, C(CH3)3), 0.94 (s, 18H, C(CH3)3); 13C NMR
(CDCl3) δ 150.6, 149.6, 146.8, 141.1, 137.0, 132.4, 128.5, 127.6,
127.5, 127.2, 125.3, 124.8, 77.9, 34.0, 33.9, 31.8, 31.6, 31.1; MS(ESI):
m/z (%) = 851 (M+ + Na, 100).
l
25,27-Bis(4-iodobenzyloxy)-26,28-dihydroxy-p-t-butylcalix[4]-
arene (3e): White needles; m.p. 248.8–250.4 °C; [lit.20 228–229 °C];
IR vmax = 3533, 3422, 3046, 2958, 2866, 1484, 1362, 1213, 872,
806 cm−1; lH NMR (CDCl3) δ 7.70 (d, J = 8.4 Hz, 4H, ArH), 7.39(d,
J = 8.0Hz, 4H, ArH), 7.14 (s, 2H, OH), 7.02 (s, 4H, ArH), 6.76 (s, 4H,
ArH), 4.97 (s, 4H, OCH2Ar), 4.21 (d, J = 13.2Hz, 4H, ArCH2Ar), 3.27
(d, J = 13.2Hz, 4H, ArCH2Ar), 1.28 (s, 18H, C(CH3)3), 0.93 (s, 18H,
C(CH3)3); 13C NMR (CDCl3) δ 150.1, 149.0, 146.7, 141.0, 137.2,
136.3, 132.0, 128.7, 127.1, 125.1, 124.6, 93.2, 76.8, 33.7, 33.6, 31.5,
31.4, 30.8; MS(ESI): m/z (%) = 1098 (M+ + NH4, 100).
25,27-Bis(4-methylbenzyloxy)-26,28-dihydroxy-p-t-butylcalix[4]-
arene (3f): White needles; m.p. 237.0–239.2 °C; IR vmax = 3418, 3047,
2952, 2864, 1483, 1361, 1198, 873, 781 cm−1; 1H NMR (CDCl3)
δ 7.50 (d, J = 8.0 Hz, 4H, ArH), 7.33 (s, 2H, OH), 7.15 (d, J = 7.6 Hz,
4H, ArH), 7.00 (s, 4H, ArH), 6.76 (s, 4H, ArH), 4.99 (s, 4H, OCH2Ar),
4.26 (d, J = 13.2 Hz, 4H, ArCH2Ar), 3.24 (d, J = 12.8 Hz, 4H,
ArCH2Ar), 2.40 (s, 6H, CH3), 1.28 (s, 18H, C(CH3)3), 0.94 (s, 18H,
C(CH3)3); 13C NMR (CDCl3) δ 150.6, 149.6, 146.7, 141.0, 137.1,
134.0, 132.5, 129.1, 127.6, 127.4, 125.3, 124.8, 77.9, 34.0, 33.9, 31.8,
31.1, 21.4; m/z (%) = 855 (M− – 1, 100); HRMS-ESI: Calcd for
C60H72NaO4 (M+Na)+: 879.5328; found: 879.5357.
Synthesis of tetra-O-arylmethyl-p-t-butylcalix[4]arenes 3j–l; general
procedure
A mixture of compound 1 (1.296 g, 2 mmol), Ba(OH)2·8H2O (1.575 g,
5 mmol), BaO (0.765 g, 5 mmol) and compound 2 (10 mmol) was
stirred at 25 °C in DMF (60 mL) for 3 h under a N2 atmosphere. The
reaction mixture was concentrated in vacuo. Water (100 mL) was
added to the residue and crude product was precipitated. Recrystalli-
sation from chloroform/methanol afforded the corresponding tetra-O-
arylmethyl-p-t-butylcalix[4]arenes 3j–l.
25,26,27,28-Tetrakis(benzyloxy)-p-t-butylcalix[4]arene (3j): White
needls; m.p. 237.7–239.9 °C; [lit.18 230–231 °C]; IR vmax = 3062,
l
2953, 2867, 1479, 1361, 1194, 870, 753 cm−1; H NMR (CDCl3)
δ 7.28–7.16 (m, 20H, ArH), 6.68 (s, 8H, ArH), 4.84 (s, 8H, OCH2Ar),
4.15 (d, J = 12.4 Hz, 4H, ArCH2Ar), 2.83 (d, J = 12.4 Hz, 4H,
ArCH2Ar), 1.05 (s, 36H, C(CH3)3); 13C NMR (CDCl3) δ 152.8, 144.5,
138.5, 134.0, 129.8, 128.1, 127.7, 125.1, 76.9, 34.2, 31.9; MS(ESI):
m/z (%) = 1031 (M+ + Na, 70), 940 (100).
Synthesis of tri-O-arylmethyl-p-t-butylcalix[4]arenes 3g–i; general
procedure
25,26,27,28-Tetrakis(4-iodobenzyloxy)-p-t-butylcalix[4]arene
(3k): White solid; m.p. 224.0–225.8 °C; IR vmax = 3060, 2958, 2866,
1480, 1193, 870, 791 cm−1; lH NMR(CDCl3) δ 7.50 (d, J = 8.0 Hz, 8H,
ArH), 6.93 (d, J = 7.6 Hz, 8H, ArH), 6.71 (s, 8H, ArH), 4.72 (s, 8H,
OCH2Ar), 4.08 (d, J = 12.8 Hz, 4H, ArCH2Ar), 2.88 (d, J = 12.4 Hz,
4H, ArCH2Ar), 1.06 (s, 36H, C(CH3)3); 13C NMR (CDCl3) δ 152.2,
144.7, 137.5, 137.0, 133.4, 131.1, 125.0, 93.5, 76.0, 33.9, 31.5;
MS(ESI): m/z (%) =1535 (M+ + Na, 87), 1536 (100); HRMS-ESI:
Calcd for C72H76I4KO4 (M+K)+: 1551.1559; found: 1551.1562.
25,26,27,28-Tetrakis(4-methylbenzyloxy)-p-t-butylcalix[4]arene
A mixture of compound 1 (1.296 g, 2 mmol), Ba(OH)2·8H2O (0.788 g,
2.5 mmol), BaO (0.383 g, 2.5 mmol) and compound 2 (6 mmol) was
stirred at 25 °C in DMF (50 mL) for 2.5 h under a N2 atmosphere.
The reaction mixture was concentrated in vacuo. Water (100 mL) was
added to the residue and the crude product was precipitated. Recryst-
allisation from chloroform/methanol afforded the corresponding
tri-O-arylmethyl-p-t-butylcalix[4]arenes 3g–i.
25,26,27-Tris(benzyloxy)-28-hydroxy-p-t-butylcalix[4]arene (3g):
White solid; m.p. 216.7–218.3 °C; [lit.21 210–214 °C]; IR vmax = 3549,
3455, 2954, 2866, 1481, 1362, 1197, 871, 752 cm−1; lH NMR (CDCl3)
(3l): White needls; m.p. 199.6–201.2 °C; [lit.18 205–207 °C]; IR vmax
=
1
3048, 2960, 2866, 1479, 1195, 869, 751 cm−1; H NMR (CDCl3) δ

406 JOURNAL OF CHEMICAL RESEARCH 2012
7.12 (d, J = 7.6 Hz, 8H, ArH), 6.98 (d, J = 7.6 Hz, 8H, ArH), 6.67 (s,
8H, ArH), 4.79 (s, 8H, OCH2Ar), 4.16 (d, J = 12.4 Hz, 4H, ArCH2Ar),
2.83 (d, J = 12.8 Hz, 4H, ArCH2Ar), 2.32 (s, 12H, CH3), 1.05 (s, 36H,
C(CH3)3); 13C NMR (CDCl3) δ 152.7, 144.0, 136.8, 135.3, 133.8,
129.6, 128.4, 124.7, 76.3, 33.9, 31.8, 31.6, 21.4; MS(ESI): m/z (%) =
1087 (M+ + Na, 100).
1.062 (s, 9H, C(CH3)3), 1.059 (s, 9H, C(CH3)3), 1.046 (s, 18H,
C(CH3)3); 13C NMR (CDCl3) δ 152.7, 152.65, 152.58, 144.11, 144.05,
138.3, 136.8, 135.3, 133.8, 133.7, 129.7, 129.6, 128.4, 127.7, 127.3,
124.8, 76.3, 33.9, 31.7, 31.6, 21.4; MS(ESI): m/z (%) = 1073 (M+ +
Na, 100); HRMS-ESI: Calcd for C75H90NO4 (M+NH4)+: 1068.6870;
found: 1068.6856.
25,27-Bis(4-methylbenzyloxy)-26,28-bis(benzyloxy)-p-t-butylcalix-
[4]arene (3q): White needles; m.p. 179.0–180.7 °C; IR vmax = 3029,
2960, 2866, 1479, 1195, 869, 752 cm−1; 1H NMR (CDCl3) δ 7.26–7.19
(m, 10H, ArH), 7.13 (d, J = 7.6 Hz, 4H, ArH), 6.99 (d, J = 7.6 Hz, 4H,
ArH), 6.69 (s, 4H, ArH), 6.66 (s, 4H, ArH), 4.85 (s, 4H, OCH2Ar),
4.78 (s, 4H, OCH2Ar), 4.15 (d, J = 12.4 Hz, 4H, ArCH2Ar), 2.83 (d,
J = 12.8 Hz, 4H, ArCH2Ar), 2.32 (s, 6H, CH3), 1.07 (s, 18H, C(CH3)3),
1.04 (s, 18H, C(CH3)3); 13C NMR (CDCl3) δ 152.6, 144.2, 144.1,
138.3, 136.9, 135.2, 133.8, 133.6, 129.61, 129.55, 128.4, 127.7, 127.3,
124.8, 124.75, 76.44, 76.37, 33.9, 31.7, 31.6, 21.4; MS(ESI): m/z (%)
= 1075 (M+ + K, 100); HRMS-ESI: Calcd for C74H88NO4 (M+NH4)+:
1054.6713; found: 1054.6705.
25-(4-Methylbenzyloxy)-26,27,28-tris(benzyloxy)-p-t-butylcalix[4]-
arene (3r): White needles; m.p. 213.2–215.0 °C; IR vmax = 3060, 2946,
2867, 1478, 1195, 870, 753 cm−1; 1H NMR (CDCl3) δ 7.25–7.16 (m,
15H, ArH), 7.14 (d, J = 8.0 Hz, 2H, ArH), 6.98 (d, J = 7.6 Hz, 2H,
ArH), 6.68 (s, 4H, ArH), 6.67 (s, 2H, ArH), 6.66 (s, 2H, ArH), 4.84 (s,
4H, OCH2Ar), 4.82 (s, 2H, OCH2Ar), 4.80 (s, 2H, OCH2Ar), 4.17 (d,
J = 10.0 Hz, 2H, ArCH2Ar), 4.14 (d, J = 9.6 Hz, 2H, ArCH2Ar), 2.85
(d, J = 5.2 Hz, 2H, ArCH2Ar), 2.81 (d, J = 4.8 Hz, 2H, ArCH2Ar), 2.31
(s, 3H, CH3), 1.06 (s, 18H, C(CH3)3), 1.05 (s, 9H, C(CH3)3), 1.046 (s,
9H, C(CH3)3); 13C NMR (CDCl3) δ 152.6, 144.2, 138.2, 136.9, 135.2,
133.8, 133.7, 129.6, 129.5, 128.4, 127.7, 127.3, 124.8, 76.5, 33. 9,
31.6, 21.4; MS(ESI): m/z (%) = 1040 (M+ + NH4, 100); HRMS-ESI:
Calcd for C73H86NO4 (M+NH4)+: 1040.6557; found: 1040.6550.
Synthesis of tetra-O-arylmethyl-p-t-butylcalix[4]arenes with two
different arylmethylic groups 3m–r; general procedure
A mixture of compound 3a (0.648 g, 1 mmol), and NaH (0.24 g,
6 mmol, 60% dispersion in oil) (using 4 mmol NaH for 3d and 2 mmol
NaH for 3g) was stirred at 25 °C in THF-DMF (40 mL, 7:1, v/v) under
a N2 atmosphere. After 20 min a solution of compound 2 (6mmol)
(using 4 mmol compound 2 for 3d and 2 mmol compound 2 for 3g)
in 10 mL THF was introduced, and the reaction mixture was stirred at
70 °C for 2 h. After cooling, a few drops of methanol were added,
and the solution was concentrated. Water (100 mL) was added to the
residue and the crude product was precipitated. Recrystallisation from
chloroform/methanol afforded the corresponding tetra-O-arylmethyl-
ated derivatives 3m–r.
25,26,27-Tris(4-iodobenzyloxy)-28-benzyloxy-p-t-butylcalix[4]-
arene (3m): White needles; m.p. 184.7–186.4 °C; IR vmax = 3056,
2956, 2866, 1479, 1193, 870, 753 cm−1; 1H NMR (CDCl3) δ 7.50 (d,
J = 7.6 Hz, 2H, ArH), 7.45 (d, J = 8.0 Hz, 4H, ArH), 7.31–7.24 (m,
5H, ArH), 6.93 (d, J = 8.0 Hz, 4H, ArH), 6.89 (d, J = 8.0 Hz, 2H,
ArH), 6.79 (s, 2H, ArH), 6.76 (s, 2H, ArH), 6.66 (s, 2H, ArH), 6.62 (s,
2H, ArH), 4.82–4.78 (m, 4H, OCH2Ar), 4.73 (d, J = 11.6 Hz, 2H,
OCH2Ar), 4.66 (s, 2H, OCH2Ar), 4.20 (d, J = 12.4 Hz, 2H, ArCH2Ar),
4.03 (d, J = 12.4 Hz, 2H, ArCH2Ar), 2.94 (d, J = 12.8 Hz, 2H,
ArCH2Ar), 2.83 (d, J = 12.8 Hz, 2H,ArCH2Ar), 1.12(s, 18H, C(CH3)3),
1.01(s, 9H, C(CH3)3), 1.00(s, 9H, C(CH3)3); 13C NMR (CDCl3) δ
152.4, 151.9, 144.7, 144.54, 144.47, 137.8, 137.6, 137.4, 136.9, 136.8,
133.9, 133.8, 133.1, 131.2, 129.3, 128.0, 127.7, 125.2, 125.0, 124.8,
93.5, 93.3, 77.2, 76.0, 75.7, 34.0, 33.9, 31.6, 31.5; MS(ESI): m/z (%)
= 1409 (M+ + Na, 100); HRMS-ESI: Calcd for C72H77I3NaO4 (M+Na)+:
1409.2854; found: 1409.2796.
25,27-Bis(4-iodobenzyloxy)-26,28-bis(benzyloxy)-p-t-butylcalix-
[4]arene (3n): White needles; m.p. 222.0–224.3 °C; IR vmax = 3056,
2956, 2866, 1479, 1193, 869, 751 cm−1; 1H NMR (CDCl3) δ 7.40 (d,
J = 8.4 Hz, 4H, ArH), 7.31–7.23 (m, 10H, ArH), 6.93 (d, J = 8.4 Hz,
4H, ArH), 6.84 (s, 4H, ArH), 6.57 (s, 4H, ArH), 4.81 (s, 4H, OCH2Ar),
4.72 (s, 4H, OCH2Ar), 4.15 (d, J = 12.8 Hz, 4H, ArCH2Ar), 2.89 (d,
J = 12.4 Hz, 4H, ArCH2Ar), 1.17 (s, 18H, C(CH3)3), 0.96 (s, 18H,
C(CH3)3); 13C NMR (CDCl3) δ 152.5, 152.2, 144.6, 144.3, 137.8,
136.7, 134.3, 132.7, 131.3, 129.3, 128.0, 127.7, 125.2, 124.7, 93.2,
77.2, 75.4, 34.0, 33.8, 31.6, 31.5, 31.4; MS(ESI): m/z (%) = 1283 (M+
+ Na, 100); HRMS-ESI: Calcd for C72H82I2NO4 (M+NH4)+: 1278.4333;
found: 1278.4272.
We are grateful to the National Natural Science Foundation
of China (No 20906083) and Natural Science Foundation
of Zhejiang Province (No Y40900488) for financial support.
We also thank Prof. T. Zhou and Dr Y. M. Ma for helpful
discussions.
Received 15 February 2012; accepted 10 April 2012
Paper 1201165 doi: 10.3184/174751912X13371837407801
Published online: 26 June 2012
References
1
2
3
4
C.D. Gutsche and J.A. Levine, J. Am. Chem. Soc., 1982, 104, 2653.
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25-(4-Iodobenzyloxy)-26,27,28-tris(benzyloxy)-p-t-butylcalix[4]-
arene (3o): White needles; m.p. 216.5–218.1 °C; [lit.20 203–204 °C];
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6
F. Santoyo-Gonzalez, A. Torres-Pinedo and A. Sanchez-Ortega, J. Org.
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1
IR vmax = 3062, 2962, 2866, 1479, 1194, 868, 751 cm−1; H NMR
(CDCl3) δ 7.41 (d, J = 8.4 Hz, 2H, ArH), 7.29–7.19 (m, 15H, ArH),
6.91 (d, J = 8.0 Hz, 2H, ArH), 6.79 (s, 2H, ArH), 6.75 (s, 2H, ArH),
6.64 (d, J = 2.4 Hz, 2H, ArH), 6.60 (d, J = 2.4 Hz, 2H, ArH), 4.89 (s,
2H, OCH2Ar), 4.83 (d, J =6.8, 1H, OCH2Ar), 4.78 (d, J =6.0, 3H,
OCH2Ar), 4.73 (d, J =11.6 Hz, 2H, OCH2Ar), 4.22 (d, J = 12.4 Hz,
2H, ArCH2Ar), 4.07 (d, J = 12.4 Hz, 2H, ArCH2Ar), 2.90 (d, J =
12.4 Hz, 2H, ArCH2Ar), 2.82 (d, J = 12.8 Hz, 2H, ArCH2Ar), 1.13 (s,
9H, C(CH3)3), 1.11(s, 9H, C(CH3)3), 1.00 (s, 18H, C(CH3)3); 13C NMR
(CDCl3) δ 152.7, 152.4, 144.5, 144.4, 144.3, 138.2, 138.0, 137.8,
136.7, 134.1, 133.2, 131.4, 129.5, 129.4, 127.9, 127.8, 127.5, 127.4,
125.0, 124.8, 124.7, 93.2, 76.9, 76.6, 75.4, 34.0, 33.9, 31.6, 31.5;
MS(ESI): m/z (%) = 1157 (M+ + Na, 100); HRMS-ESI: Calcd for
C72H83INO4 (M+NH4)+: 1152.5367; found: 1152.5318.
7
8
9
C.D. Gutsche and K.C. Nam, J. Am. Chem. Soc., 1988, 110, 6153.
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25,26,27-Tris(4-methylbenzyloxy)-28-benzyloxy-p-t-butylcalix[4]-
arene (3p): White needles; m.p. 185.1–186.8 °C; IR vmax = 3432,
3026, 2951, 2865, 1479, 1195, 869, 751 cm−1; 1H NMR (CDCl3)
δ 7.24–7.19 (m, 5H, ArH), 7.14 (d, J = 7.6 Hz, 2H, ArH), 7.12(d,
J = 7.6 Hz, 4H, ArH), 6.99 (d, J = 7.6 Hz, 6H, ArH), 6.68 (d, J =
2.8 Hz, 4H, ArH), 6.66 (s, 4H, ArH), 4.83 (s, 2H, OCH2Ar), 4.80 (s,
2H, OCH2Ar), 4.79 (s, 4H, OCH2Ar), 4.17 (d, J = 10.8 Hz, 2H,
ArCH2Ar), 4.14 (d, J = 10.8 Hz, 2H, ArCH2Ar), 2.84 (d, J = 5.2 Hz,
2H, ArCH2Ar), 2.81 (d, J = 4.8 Hz, 2H, ArCH2Ar), 2.32 (s, 9H, CH3),
16 K. Iwamoto, K. Araki and S. Shinkai, Tetrahedron, 1991, 47, 4325.
17 L.C. Groenen, B.H.M. Ruel, A. Casnati, W. Verboom, A. Pochini,
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