Preparation of 4′,4″ (5″)-Di-tert-butyldibenzo-18-crown-6 based on electrophilic aromatic substitution

Article abstract of DOI:10.1246/cl.2012.274

4′,4″ (5″)-Di-tert-butyldibenzo-18-crown-6 (DTBB18C6) was synthesized by improving the electrophilic aromatic substitution of dibenzo-18-crown-6 (DB18C6) using tert-butyl alcohol (TBA) as alkylation reagent, H₃PO₄ (85 wt%) as catalyst and CH ₂Cl₂ as solvent. Experimental results show that the optimized reaction conditions were 0.03 mol L^-1 for TBA concentration, 2.5 for TBA/DB18C6 molar ratio, 0.006 mol L^-1 for H₃PO₄ concentration, 50 °C reaction temperature, and 6 h reaction time. Under the optimum reaction conditions, DTBB18C6 yield can reach 43.65%.

Full text of DOI:10.1246/cl.2012.274

doi:10.1246/cl.2012.274
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Published on the web February 25, 2012
Preparation of 4¤,4¤¤(5¤¤)-Di-tert-butyldibenzo-18-crown-6 Based
on Electrophilic Aromatic Substitution
Juan Fan, Chunhai Yi, Xiaorong Lan, and Bolun Yang*
Department of Chemical Engineering, State Key Laboratory of Multiphase Flow in Power Engineering,
Xi’an Jiaotong University, Xi’an, Shaanxi 710049, P. R. China
(
Received December 12, 2011; CL-111186; E-mail: blunyang@mail.xjtu.edu.cn)
4
¤,4¤¤(5¤¤)-Di-tert-butyldibenzo-18-crown-6
(DTBB18C6)
0.010 mol) and H3PO4 (100 mL) were put in a funnel to add
dropwise. The reaction was kept 6 h at 60 °C. 500 mL distilled
water and 50 mL dichloromethane were added to the reaction
mixture. The organic phase was separated and distilled in vacuo.
Column chromatography was used to obtain the DTBB18C6 as
was synthesized by improving the electrophilic aromatic
substitution of dibenzo-18-crown-6 (DB18C6) using tert-butyl
alcohol (TBA) as alkylation reagent, H3PO4 (85 wt %) as catalyst
and CH2Cl2 as solvent. Experimental results show that the
optimized reaction conditions were 0.03 mol L
concentration, 2.5 for TBA/DB18C6 molar ratio, 0.006 mol L
for H3PO4 concentration, 50 °C reaction temperature, and 6 h
reaction time. Under the optimum reaction conditions,
DTBB18C6 yield can reach 43.65%.
¹
1
¹1
for TBA
white crystals. Mp: 105­110 °C; IR (¯max/cm ): 2960, 2871
¹1
(C(CH ) ), 1266 (Ar­O­C), 1216, 1147 (C­O­C), 964, 887, 802
3
3
1
(1,2,4-subs, benzene); H NMR: ¤ 0.95­1.42 (18H, s, C(CH3)3),
3.82­4.26 (16H, m, CH2OCH2), 6.70­6.98 (6H, m, ArH); Anal.
Calcd for C H O : C, 71.2; H, 8.5%. Found: C, 71.16; H,
2
8
40
6
8
.80%.
The DTBB18C6 yield and DB18C6 conversion were
defined as follows:
Nowadays, with the development of the nuclear energy
industry, a large volume of high-level nuclear waste (HLW) has
been produced and it is necessary to remove Cs from HLW
DTBB18C6 yield=%
moles of DTBB18C6 formed
137
1
137
for safe disposal. Among the methods for separating Cs from
HLW, liquid extraction has been particularly attractive. For
liquid extraction, DTBB18C6 was reported to be an extractant
with remarkable ability of complexation and transportation of
¼
ꢀ 100%
ð1Þ
initial moles of DB18C6
DB18C6 conversion=%
moles of DB18C6 converted
1
37
2
Cs.
Since Pedersen first synthesized DTBB18C6 in 1967,
¼
ꢀ 100%
ð2Þ
initial moles of DB18C6
only a few papers had reported other synthesis methods of
DTBB18C6. One of the approaches for the synthesis of
where the moles of DTBB18C6 formed, moles of DB18C6
converted, and initial moles of DB18C6 were determined from
HPLC of the reaction mixture.
3
alkyldibenzo-crown ethers is based on the electrophilic aromatic
substitution of the catechol units of the parent macrocycle.
Tashmukhamedova had used this strategy to synthesize
DTBB18C6 using TBA and PPA with a yield of 15%.4
However, because of the high activity of the tert-butyl
group, the multi-tert-butyl-substituted dibenzo-18-crown-6 is
formed easily, which will lead to a low yield of DTBB18C6.
The purpose of this article is to improve the DTBB18C6
synthesis process of electrophilic aromatic substitution (SE1) by
using more proper alkylation reagents, catalysts, and solvents to
obtain DTBB18C6 in a better yield.
Three-alkylation-reagent effects were studied in this experi-
ment. It was found that there is no remarkable difference in
DTBB18C6 yield when different alkylation reagents were used
(Figure 1). That is probably due to their similar activities in SE1
5
reaction, when PPA was employed as catalyst. Considering the
toxicities of 1-chloro-2-methylpropane and 1-bromo-2-methyl-
propane, TBA is the desired alkylation reagent.
DTBB18C6 was prepared according to the method shown in
Scheme 1. DB18C6 (compound 3, 0.005 mol) was solved in
solvents (100 mL). The mixture of tert-butyl alcohol (TBA,
Figure 1. The effect of alkylation reagents on DTBB18C6
yield (PPA as catalyst and no solvent).
Scheme 1. The synthesis procedure of DTBB18C6.
Chem. Lett. 2012, 41, 274­276
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

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Figure 4. The effect of TBA concentration on DTBB18C6
yield and DB18C6 conversion (H3PO4 concentration: 0.006
mol L , TBA/DB18C6 molar ratio: 2.5, reaction time: 6 h,
reaction temperature: 50 °C).
Figure 2. The effect of catalysts on DTBB18C6 yield (TBA as
alkylation reagent and no solvent).
¹
1
Figure 3. The effect of solvents on DTBB18C6 yield (H PO
as catalyst and TBA as alkylation reagent).
3
4
Figure 5. The effect of TBA/DB18C6 molar ratio on
DTBB18C6 yield and DB18C6 conversion (H3PO4 concen-
tration: 0.006 mol L , TBA concentration: 0.03 mol L , reac-
tion time: 6 h, reaction temperature: 50 °C).
¹
1
¹1
This reaction is an electrophilic aromatic substitution (SE1),
catalyst is used to react with alkylation reagent to form
carbonium ions. Because the higher stability of carbonium ions
is helpful to the product yield, it is necessary for catalyst to
7
this reaction. The highest DTBB18C6 yield is found when the
¹
1
TBA concentration is 0.03 mol L , meanwhile the DB18C6
conversion is up to its equilibrium value (96%). DTBB18C6
yield rises quickly at low TBA concentration (less than
6
have more remarkable ability of offering proton. As Figure 2
displayed, the highest yield (25.77%) is found when H3PO4 was
employed. It can be explained that H PO as a medium acid
¹
1
0.03 mol L ). When the TBA concentration is higher than
3
4
¹
1
has significant ability of offering proton compared with other
catalysts. Thus, H3PO4 is believed to be the proper catalyst in
this reaction.
0.03 mol L , DTBB18C6 yield decreases with the increasing
concentration. It shows that increasing the TBA concentration at
a low level will promote the reaction process and increase the
DTBB18C6 yield.
In strong polar solvent, the alkylation reagents will be
6
solvated and its efficient concentration will be lower. Poor polar
Further research focusing on the influence of different
TBA/DB18C6 molar ratios is needed. The DB18C6 conversion
is up to its equilibrium value (96%) in this reversible reaction
when the TBA/DB18C6 molar ratio is more than 2.5 (Figure 5).
Nevertheless, with the continued increase of TBA/DB18C6
molar ratio the side reaction leading to the synthesis of multi-
tert-butyl-substituted dibenzo-18-crown-6 will also be enhanced,
solvent is also harmful for the product yield because the process
of the opposite-sign charges separating to form carbonium ions
6
does not occur in poor polar solvent easily. When CH2Cl2 is
used as solvent, DTBB18C6 yield increases to 36.21% which is
the highest yield in Figure 3. Therefore, CH Cl is the proper
2
2
solvent with moderate polarity for the synthesis of DTBB18C6.
The changes of DTBB18C6 yield and DB18C6 conversion
with TBA concentration are presented in Figure 4. Generally
speaking, increasing the concentration of alkylation reagent will
increase the product yield too. However, at a higher TBA
concentration, DTBB18C6 yield will be result in a fall due to the
generation of multi-tert-butyl-substituted dibenzo-18-crown-6 in
7
which gives rise to the decline of the DTBB18C6 yield.
The side reaction will also be enhanced at high concen-
6
tration of H3PO4. It may be easier to generate multi-tert-butyl-
substituted dibenzo-18-crown-6 than DTBB18C6 at high H3PO4
concentration. Figure 6 displays that when the H PO concen-
3
4
¹
1
tration is 0.006 mol L , DTBB18C6 yield could reach to its
Chem. Lett. 2012, 41, 274­276
© 2012 The Chemical Society of Japan www.csj.jp/journals/chem-lett/

2
76
Figure 6. The effect of H3PO4 concentration on DTBB18C6
yield and DB18C6 conversion (TBA concentration: 0.03
mol L , TBA/DB18C6 molar ratio: 2.5, reaction time: 6 h,
reaction temperature: 50 °C).
Figure 8. The effect of reaction temperature on DTBB18C6
yield and DB18C6 conversion (TBA concentration: 0.03
¹1
¹1
mol L , TBA/DB18C6 molar ratio: 2.5, H3PO4 concentration:
¹
1
0.006 mol L , reaction time: 6 h).
DTBB18C6 yield rises quickly with temperature increasing at
low reaction temperature (less than 50 °C). When the temper-
ature is higher than 50 °C, DTBB18C6 yield declines with the
increasing temperature. In addition, equilibrium value (96%) of
DB18C6 conversion could be seen when the temperature is more
than 50 °C.
TBA is the desired alkylation reagent for its lower toxicity.
Increasing the TBA concentration at a low level (less than
¹
1
0
.03 mol L ) will increase the DTBB18C6 yield. The optimum
TBA/DB18C6 molar ratio is about 2.5, and increasing ratio is
beneficial to DTBB18C6 yield when the ratio is below 2.5.
H3PO4 has significant ability to offering protons comparing to
other acid catalysts, and H3PO4 is believed to be the proper
catalyst for DTBB18C6 synthesis. DTBB18C6 yield increases
significantly when CH2Cl2 is used as solvent. The experimental
results also show the optimum reaction temperature and time is
Figure 7. The effect of reaction time on DTBB18C6 yield and
¹
1
DB18C6 conversion (TBA concentration: 0.03 mol L , TBA/
¹
1
DB18C6 molar ratio: 2.5, H3PO4 concentration: 0.006 mol L
reaction temperature: 50 °C).
,
5
0 °C and 6 h, respectively.
The financial support from Key Project of National High
maximum of 43.65% (Figure 6). The DB18C6 conversion
reaches its equilibrium value (96%) when the H PO concen-
Technology Research and Development Program (863 Program)
of China (No. 2009AA050703) is gratefully acknowledged.
3
4
¹
1
tration is more than 0.008 mol L
.
As with many reversible reactions, extending reaction time
will increase the product yield. However, longer reaction time
would cause the side reaction of DTBB18C6 with TBA, which
References and Notes
1
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Saifullina, M. G. Levkovich, Chem. Heterocycl. Compd.
1986, 22, 1178.
will lead to the synthesis of multi-tert-butyl-substituted dibenzo-
6
1
8-crown-6 and a decrease in the DTBB18C6 yield. There is an
optimum reaction time (6 h) for DTBB18C6 synthesis, as
Figure 7 depicts. DTBB18C6 yield increases straightly until it
reaches the highest value (43.65%) in a short reaction time (less
than 6 h). When the time exceeds 6 h, DTBB18C6 yield reduces
with time. The equilibrium value of DB18C6 conversion
appears at about 6 h. It can be easily explained that with the
time increase, the DTBB18C6 will reach its equilibrium yield
gradually. Hence it is important to control the reaction time
strictly.
Alkylation is an exothermic reaction, and the effect of
reaction temperature on DTBB18C6 yield is supposed to be
that increasing temperature is unfavorable for DTBB18C6
yield when it is at high level. As Figure 8 showed, there is
an optimum reaction temperature (50 °C) in this reaction.
2
3
4
5
6
F. A. Carey, Organic Chemistry, 4th ed., McGraw-Hill
Higher Education, Boston, 2000.
M. B. Smith, J. March, Advanced Organic Chemistry:
Reactions, Mechanisms, and Structure, McGrow-Hill Inc.,
New York, 1977.
7
Crown Ether Chemistry, Japan Chemical Supplement, ed. by
R. Oda, T. Shono, I. Tabuse, Tokyo, 1978.
Chem. Lett. 2012, 41, 274­276
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/