Facile one-pot synthesis of aliphatic bridged diaryloxy compounds, cyclic and crown ethers under mild conditions

Article abstract of DOI:10.1080/10610278.2016.1267858

We report here the facile, room temperature, catalyst free, one pot synthesis of aliphatic bridged diaryloxy compounds, cyclic and crown ethers. Anhydrous potassium carbonate (K₂CO₃) as a mild base along with dimethyl sulfoxide gener

Full text of DOI:10.1080/10610278.2016.1267858

Supramolecular Chemistry
ISSN: 1061-0278 (Print) 1029-0478 (Online) Journal homepage: http://www.tandfonline.com/loi/gsch20
Facile one-pot synthesis of aliphatic bridged
diaryloxy compounds, cyclic and crown ethers
under mild conditions
Sachin Sakate, Sumit Kamble, Rajiv Chikate & Chandrashekhar Rode
To cite this article: Sachin Sakate, Sumit Kamble, Rajiv Chikate & Chandrashekhar Rode (2017)
Facile one-pot synthesis of aliphatic bridged diaryloxy compounds, cyclic and crown ethers under
mild conditions, Supramolecular Chemistry, 29:6, 462-470, DOI: 10.1080/10610278.2016.1267858
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Date: 18 March 2017, At: 22:11

Supramolecular chemiStry, 2017
Vol. 29, No. 6, 462–470
http://dx.doi.org/10.1080/10610278.2016.1267858
Facile one-pot synthesis of aliphatic bridged diaryloxy compounds, cyclic and
crown ethers under mild conditions
Sachin Sakatea,b, Sumit Kamblea, Rajiv Chikatec and Chandrashekhar Rodea
acSir-National chemical laboratory, pune, india; bp. e. Society’s, modern college of arts, Science and commerce, Shivajinagar, pune, india; cm. e.
Society’s, abasaheb Garware college, pune, india
ABSTRACT
ARTICLE HISTORY
received 13 august 2016
accepted 29 November 2016
We report here the facile, room temperature, catalyst free, one pot synthesis of aliphatic bridged
diaryloxy compounds, cyclic and crown ethers. Anhydrous potassium carbonate (K2CO3) as a mild
base along with dimethyl sulfoxide generates the phenoxide ion which facilitates the nucleophilic
substitution of bromoalkanes to yield the corresponding crown ethers.
KEYWORDS
crown ethers; cyclic ethers;
aliphatic bridged diaryloxy
compounds
Introduction
the host-guest and also the supramolecular chemistry.
(4a–d) There is an excellent correlation of the stability of
these complexes with the size of the cation and that of
the cavity in the macrocyclic ligand. Crown ethers have
also been used successfully for chiral recognition by selec-
tive binding to one of the enantiomers, thereby poten-
tially providing a technique for optical resolution. (4d)
Increasing the number of benzo substituents in a crown
Aliphatic bridged diaryloxy compounds are used as impor-
tant intermediates for the synthesis of various types of
crown and thio crown ethers, (1a–c) polybenzoxazines,
(2) basket handled porphyrin units etc. (3a–b) Cyclic and
crown ethers have the ability to bind strongly to form the
most stable complexes with the alkali metal and alkaline
earth metals which contribute significantly to elucidate
CONTACT chandrashekhar rode
cv.rode@ncl.res.in
the supplemental data for this paper is available online at http://dx.doi.org/10.1080/10610278.2016.1267858.
© 2016 informa uK limited, trading as taylor & Francis Group

SUPRAMOLECULAR CHEMISTRY
463
O
n
n
Br
O
O
Br
R' Br
R'
R
R
R
OH
R
K2CO3 / DMSO
R
n
O
O
HO
OH
O
O
O
O
O
O
R
R
O
R
R
O
O
n
Br
Br
Br
Br
n
Scheme 1. (colour online) Synthesis of alkyl aryl ether, aliphatic bridged diaryloxy compounds, crown ethers, cyclic ethers.
ether framework can significantly alter the properties
of the ligand. Generally, adding benzo substituent will
increase the rigidity of the crown ether framework and
enhance its lipophilicity (5) but will decrease the basicity of
the oxygen atoms attached to the aromatic rings. Several
methods are reported in the literature for the synthesis of
alkyl aryl ethers which are complementary to the tradi-
tional Williamson ether synthesis. Some of these involve
the direct nucleophilic substitution of activated aryl hal-
ides, (6a–d) Cu (I)-catalysed cross-coupling of alkoxides
with aryl halides (7a–e) and palladium-catalysed synthe-
sis of protected phenols from aryl halides. (8a–d) Various
catalytic and noncatalytic methods have been reported for
the synthesis of the aliphatic bridged bisphenols, crown
ethers, cyclic ethers and also for the protection of the phe-
nols (Ar-OH), aromatics amines (Ar-NHR’) and thiophenols
(Ar-SH) which include the use of NaH/THF, TEGDT, (9a)
CeO2/KOH, DMSO, (9b) TBDMSCl/I2, microwave, (9c) DMS,
NaH/THF, (9d) K2CO3, KI, (9e) RX, KF, acetone, (9f) etc. All
these methods, report the reactions at elevated temper-
atures, use of metals, multistep synthesis, long reaction
times and the cumbersome work up of the reaction crude.
To overcome all these limitations we streamlined a
facile, single-pot and noncatalytic synthesis of the alkoxy
substituted aromatic compounds at ambient reaction
conditions using K2CO3/DMSO. The developed method is
equally applicable for the synthesis of the aliphatic bridged
diaryloxy, oxy-bis-alkane diaryloxy compounds, cyclic and
crown ethers and also for the protection of phenolic –OH
and aromatic amines (Ar-NHR’) by using the different alkyl
halides (Scheme 1). The use of different dihalides with var-
ying number of methylene groups was found to be the
most convenient way for manipulating the ring size of the
cyclic and crown ethers which can enhance their ability for
the extraction of various types of the metal ions, mainly
having the application for the extraction of radioactive
elements (10). Also this strategy may be useful to reduce
the steric interaction of the substituents present on the
aromatic nucleus resulting into collapsing inside during
the formation of the cyclic ring of the ether. All these sub-
stituents further may be used for the construction as the
handles of the crown ethers like baskets for the porphyrin
molecules (11a–b).
Results and discussion
In this work, alkylation of various substituted phenols was
achieved at an ambient temperature through nucleophilic
substitution involving different alkylating agents such as
allyl, prenyl, benzyl bromides in presence of K2CO3/DMSO.
The phenolic –OH was protected by alkyl, aryl, prenyl,
benzyl protecting groups to form the corresponding aryl
alkyl ethers (Table 1). Entries 1–16 in Table 1 show that
phenol with various substituents reacts efficiently with
all the three types of alkyl as well as benzyl bromides to
give the corresponding ethers in 75–94% yields. It is very
interesting to note that for resacetophenone containing
two –OH groups, only the 4-position reacts to give the
corresponding ethers in 81% and 82% yields, respectively
(Table 1, entries 3–4), thus establishing the regeoselective
alkylation. Regeoselectivity is possible due to the intra-
molecular hydrogen bonding between carbonyl oxygen
and the phenolic–OH and its sterically hindered 2-position.
The maximum yield of 92% was achieved in case of p-nitro
phenol (Table 1, entry 5) due to the highest electron with-
drawing ability of –NO2 group at p-position. On the other
hand, lower yields (75–79%) were obtained as expected,
due to the electron donating effect of –CH3 group (Table
1, entry 3–7). As compared to alkyl substituted phenols,
chloro, acetyl, formyl and hydroxy substituted phenols
gave much higher yield >80% which could be due to more
pronounced electron withdrawing nature of functional

464
S. SAKATE ET AL.

SUPRAMOLECULAR CHEMISTRY
465

466
S. SAKATE ET AL.
groups present on the aromatic nucleus (Table, entry 1,
2 and 8, 9).
As a further extension of our methodology, synthesis
of aliphatic bridged diaryloxy compounds with various
substituents was achieved in excellent yields (86–92%),
which serve as intermediates for the synthesis of the cyclic
and crown ethers by reacting substituted phenols with
dihaloalkanes like, 1,3-dibromopropane, 1,4-dibromobu-
tane, 1-bromo-2-(2-bromoethoxy) ethane etc. (Table 2,
entries 1–9). To start with, salicylaldehyde and the cor-
responding ketones (o-hydroxy acetophenone) were
efficiently reacted with 1,3-and 1,4-dibromoalkanes to
give more than 90% yield of the corresponding aliphatic
bridged diaryloxy compounds having carbon atoms var-
ying between 3 and 4 (Table 2, entries 1–6). Both ortho
and para nitro phenols were also reacted with 1,4-dibromo
butane to give excellent yields of the aliphatic bridged
diaryloxy compounds (Table 2, entries 7, 8). Another alky-
lating agent such as 1-bromo-2-(2-bromoethoxy) ethane
was chosen to react with orcinol (3,5-dimethyl phenol) in
order to obtain oxybisalkane diaryloxy compound in 76%
yield (Table 2, entry 9). N-alkylation was also attempted
with acetanilide expecting that acidic proton attached
to nitrogen could be easily substituted by the alkylating
agent. On the contrary, the yield of the corresponding ali-
phatic bridged di-acetanilide compound achieved was less
than 50% (Table 2, entry 10).
After the successful O-alkylation of the substituted
phenols, N-alkylation of acetanilide and the synthesis of
the aliphatic bridged diaryloxy compounds, our approach
was further extended for one pot synthesis of cyclic and
the crown ethers in which two moles of each substituted
dihydroxy benzene and alkyl halide were used. The cav-
ity size created during the synthesis of cyclic and crown
ethers could be easily tailored by varying the ring size
from sixteen to twenty atoms. Table 3, entries 1, 2 and 7
clearly demonstrate the efficient synthesis of cyclic ethers
with varying cavity sizes by employing various dibromo
alkanes such as 13-dibromopropane, 14-dibromobutane
and 15-dibromopentane. Similarly, crown ethers were syn-
thesised by reacting 1-(2,4-dihydroxyphenyl) propan-1-
one with 1-bromo-2-(2-bromoethoxy) ethane at ambient
conditions (Table 3, entries 3 and 6). Table 3, entries 4 and 5
show the examples of novel cyclic and crown ethers where,
both the ketone groups attached to the benzene ring
could collapse inside the ring cavity by using 1-(2,6-dihy-
droxyphenyl) ethan-1-one and the dihalo alkanes.
Experimental section
All chemicals and reagents were procured from com-
mercial suppliers and used without further purification.
The products were characterised using 1H NMR, 13C NMR

SUPRAMOLECULAR CHEMISTRY
467
Table 2. Synthesis of aliphatic bridged diaryloxy compounds.
Entry
Reactant
Alkyl halide
Product
% yield
1
89
2
85
3
4
81
82
5
6
92
78
7
87
8
9
86
76
10
49
areaction conditions: phenol (2 mmol), dihaloalkane (1 mmol), anhydrous K2co3 (2 mmol), DmSo (10 ml), time (4–6 h).
byields of isolated products are reported.
spectra. NMR spectrums of product were obtained using
Bruker AC-200 MHz spectrometer with TMS as the inter-
nal standard. Column chromatography was performed
on silica gel, Merck grade 60–120 mesh size. TLC was per-
formed on 0.25 mm E. Merck precoated silica gel plates
(60 F254).

468
S. SAKATE ET AL.
Table 3. Synthesis of cyclic and crown ethers.
% Yieldb
Entry
Reactant
Alkyl halide
Product
1
74
2
3
78
76
4
72
5
6
82
80
7
78
(Continued)

SUPRAMOLECULAR CHEMISTRY
469
Table 3. (Continued).
% Yieldb
84
Entry
Reactant
Alkyl halide
Product
8
areaction conditions: phenol (2 mmol), dihaloalkane (2 mmol), anhydrous K2co3 (4 mmol), DmSo (10 ml) time (6–8 h).
byields of isolated products are reported.
carbonate (4 mmol, 0.552 gm) was added in small
portions and the solution was stirred continuously
maintaining the inert atmosphere. To the above yellow
coloured solution, 1, 4-dibromo butane (2 mmol, 0.432
gm) was injected with syringe. The reaction mixture
was stirred for 6–8 h. The completion of the reaction
was monitored by TLC and the reaction mixture was
extracted with dichloromethane (2 × 20 mL), washed
two times with dil. HCl (2N) to neutralise the potas-
sium carbonate. Finally, the mixture was washed with
ice cold water. The organic layer was treated with anhy-
drous sodium sulfate and evaporated under reduced
pressure. A colourless oily product was obtained which
was further characterised by IR, NMR spectroscopy and
HRMS techniques.
Typical procedure for synthesis of aliphatic bridged
diaryloxy compounds (Table 1, entry 1)
To a solution of 2,4-dichloro phenol (1 mmol, 0.244 gm) in
DMSO (10 mL), anhydrous potassium carbonate (1 mmol,
0.138 gm) was added in small portion and the solution was
stirred continuously maintaining the inert atmosphere. To
the above yellow coloured solution, 1,4-dibromo butane
(1 mmol, 0.121 gm) was injected with syringe. The reaction
mixture was stirred for 2 h. The completion of the reaction
was monitored by TLC and reaction mixture was extracted
with ethyl acetate (5 mL), washed two times with dil. HCl
(2N) to neutralise the potassium carbonate. Finally the mix-
ture was washed with ice cold water. The organic layer was
treated with anhydrous sodium sulfate and evaporated
under reduced pressure. A white coloured solid product
was obtained which was further characterised by IR, NMR
spectroscopy and HRMS technique.
Conclusions
We have successfully demonstrated one pot method for
the synthesis of some novel crown ethers, cyclic ethers
(72–84%) and the aliphatic bridged diaryloxy and oxybis-
alkane diaryloxy compounds (82–90%) at ambient con-
ditions using K2CO3/DMSO. Various types of substituted
phenols and different dihalo alkane compounds were
used for the synthesis of the aliphatic bridged diaryloxy
compounds in one pot method which is very useful in
the polymer chemistry applications for the synthesis of
polybenzoxazines. The aliphatic bridge between the two
phenol rings was very easily tailored by using dibromo
propane, dibromo butane, dibromo pentane etc. Cyclic
ethers and the crown ethers were also synthesised in
one pot by varying the alkylating reagents (dibromo
propane, dibromo butane, 2-bromo ethyl ether etc.).
The ring size of the crown ether and the cyclic ethers
can be further increased by the selection of the various
dihalides which are known to be very suitable for the
extraction of various types of metals including the radio-
active elements and also for the resolution of the optical
isomers. The carbonyl group attached to the phenols
were shown to be easily collapsible inside the crown
ether cavities, thereby minimising the steric interaction
in the resultant compounds.
Typical procedure for synthesis of aliphatic bridged
diaryloxy compounds (Table 2, entry1)
To a solution of salicylaldehyde (2 mmol, 0.244 gm) in
DMSO (10 mL), anhydrous potassium carbonate (2 mmol,
0.276 gm) was added in small portion and the solution was
stirred continuously maintaining the inert atmosphere. To
the above yellow coloured solution, 1,4-dibromo butane
(1 mmol, 0.216 gm) was injected with syringe. The reac-
tion mixture was stirred for 2–4 h. The completion of the
reaction was monitored by TLC and reaction mixture was
extracted with ethyl acetate (20 mL), washed two times
with dil. HCl (2N) to neutralise the potassium carbonate.
Finally the mixture was washed with ice cold water. The
organic layer was treated with anhydrous sodium sulfate
and evaporated under reduced pressure. A white coloured
solid product was obtained which was further character-
ised by IR, NMR spectroscopy and HRMS technique.
Typical procedure for synthesis of cyclic ethers and
crown ethers (Table 3, entry 5)
To a solution of 2,6-dihydroxy acetophenone (2 mmol,
0.304 gm) in DMSO (10 mL), anhydrous potassium

470
S. SAKATE ET AL.
React. Inorg. & Org. Metal Chem. 1986, 16, 1363–1369; (c)
Pearson, A.; Ann, M.; Gelormini, J. J. Org. Chem. 1994, 59,
4561–4570; (d) Thomas, F.; Christoph, R.; Thomas, J. J. Org.
Chem. 1998, 63, 9594–9596.
Acknowledgements
One of the authors Sachin S. Sakate working at P. E. Society’s
Modern college of Arts, Science and Commerce, Shivajinagar,
Pune-411005, is grateful to UGC-Delhi for the award of FIP (Fac-
ulty Improvement Programme) fellowship to carry out the re-
search work at CSIR-National Chemical Laboratory, Pune India
(7) (a) Whitesides, G.; Sadowski, J.; Lilburn, J. J. Am. Chem. Soc.
1974, 96, 2829–2835; (b) Lindley, J. Tetrahedron 1984, 40,
1433–1456; (c) Aalten, H.; Koten, G.; Grove, D.; Kuilman, T.;
Piekstra, O.; Hulshof, L.; Sheldon, R. Tetrahedron 1989, 45,
5565–5578; (d) Aalten, H.; Koten, G.; Grove, D.; Kuilman,
T.; Piekstra, O.; Hulshof, L.; Sheldon, R. Tetrahedron 1992,
48, 3652–3633; (e) Keegstra, M.; Peters, T.; Brandsma, L. J.
Am. Chem. Soc. 1996, 118, 10333–10334; (f) Capdevielle, P.;
Maumy, M. Tet. lett. 1993, 34, 1007–1010.
Disclosure statement
No potential conflict of interest was reported by the authors.
(8) (a) Mann, G.; Hartwig, J. J. Am. Chem. Soc. 1996, 118,
13109–13110; (b) Mann, G.; Hartwig, J. J. Org. Chem.
1997, 62, 5413–5418; (c) Palucki, M.; Wolfe, J.; Buchwald,
S. J. Am. Chem. Soc. 1996, 118, 10333–10334; (d) Torraca,
K.; Kuwabe, S.; Buchwald, S. J. Am. Chem. Soc. 2000, 122,
12907–12908.
(9) (a) Karakaplan, M.; Devran, A.; Colak, M.; Kocakaya, S.;
Hos, H.; Pirinccioglu Goren, N. Tetrahedron 2013, 69,
349–358; (b) Agawane, S.; Nagarkar, J. Tet. Lett. 2006, 47,
3521–3523; (c) Roy, V.; Colombeau, L.; Zerrouki, R.; Krausz,
P. Carbohydrate Res. 2004, 339, 1829–1831; (d) Chou, T.;
Chen, S.; Chen, Y. Tetrahedron 2003, 59, 983–993; (e) Zhao,
J.; Ge, M.; Qu, Z. Inorg. Chem. Commun. 2010, 13, 1152–
1155; (f) Lamouchi, M.; Jeanneau, E.; Chiriac, R.; Ceroni, D.;
Meganem, F.; Brioude, A.; Coleman, A.; Desroches, C. Tet.
Lett. 2012, 53, 2088–2090.
References
(1) (a) Gibson, H.; Wang, H.; Bonrad, K.; Jones, J.; Slebodnick, C.;
Zackharov, L.; Rheingold, A.; Habenicht, B.; Lobue, P.; Ratliff,
A. Org. Biomol. Chem. 2005, 3, 2114–2121; (b) Delaviz, Y.;
Gibson, H. Macromolecules 1992, 25, 18–20; (c) Çiçek, B.;
Yıldız, A. Molecules 2011, 16, 8670–8683.
(2) Baranek, A.; Kendrick, L.; Narayanan, J.; Tyson, G.; Wand, S.;
Patton, D. Polymer Chemistry 2012, 28, 2892–2900.
(3) (a) Momenteau, M.; Mispelter, J.; Loock, B.; Bisagni, E. J.
Chem. Soc. Perkin Trans. 1983, I, 189–196; (b) Simonis, U.;
Walker, F.; Lee, P.; Hanquet, B.; Meyerhoff, D.; Scheidts, W. J.
Am. Chem. Soc. 1987, 109, 2659–2668.
(4) (a) Newcomb, M.; Timko, J.; Walba, D.; Donald, J. J. Am.
Chem. Soc. 1977, 99, 4207–4219; (b) Moore, S.; Tarnowski,
T.; Newcomb, M.; Cram, D. J. Am. Chem. Soc. 1977, 99, 6398–
6405; (c) Newcomb, M.; Moore, S.; Cram, D. J. Am. Chem.
Soc. 1977, 99, 6405–6410; (d) Cram, D.; Helgeson, R.; Sousa,
L.; Timko, J.; Newcomb, M.; Moreau, P.; De Jong, F.; Gokel, G.;
Hoffman, D.; Domeier, L.; Peacock, S.; Madan, K.; Kaplan, K.
Pure and Appli. Chem. 1975, 43, 327–350.
(10) Vyas, C.; Joshirao, P.; Shukla, R.; Tyagi, A.; Manchanda, V.J.
Hazard. Mater. 2012, 241, 340–347.
(11) (a) Gunter, M.; Johnston, M.; Skelton, B.; White, A. J. Chem.
Soc. Perkin Trans. 1 1994, 1007–1010; (b) Deutman, A.;
Woltinge, T.; Smits, J.; De Gelder, R.; Elemans, J.; Nolte, R.;
Rowan, A. Molecules 2014, 19, 5278–5300.
(5) Pedersen, C.J. J. Am. Chem. Soc. 1967, 89, 7017–7036.
(6) (a) DeVries, V.; Moran, D.; Allen, G.; Riggi, S. J. Med. Chem.
1976, 19, 946–957; (b) Hamilton, J.; Mehaffy, C. Synth.