A new alkylation of aryl alcohols by boron trifluoride etherate

Article abstract of DOI:10.3390/molecules24203720

The ethylation of aryl alcohols by an ethyl moiety of boron trifluoride etherate is described. The reaction proceeded cleanly and afforded good yields of the corresponding aryl ethyl ethers. It tolerated the presence of functional groups such as aryl, alkyl, halogens, nitro, nitrile, and amino. However, the presence of amino or nitro groups ortho to a hydroxyl group of an aryl compound drastically reduced the yields of the anticipated products due to the chelation of the aforementioned functional groups with boron trifluoride etherate. A nitrogen atom in the aromatic ring system, as exemplified by hydroxypyridine and 8-hydroxyquinoline, completely inhibited the reaction. Resorcinol, hydroquinone, and aryl alcohols with aldehyde functions decomposed under the reaction conditions.

Full text of DOI:10.3390/molecules24203720

molecules
Article
A New Alkylation of Aryl Alcohols by Boron
Trifluoride Etherate
Ndze Denis Jumbam, Yamkela Maganga, Wayiza Masamba * , Nomthandazo I. Mbunye,
Esethu Mgoqi and Sphumusa Mtwa
Department of Chemical and Physical Sciences, Faculty of Natural Sciences, Walter Sisulu University, Nelson
Mandela Drive, Mthatha 5117, South Africa; njumbam@wsu.ac.za (N.D.J.); magangayamkela@gmail.com (Y.M.);
mbunyenomthandazo@gmail.com (N.I.M.); esemgoqi12@gmail.com (E.M.); mtwasphumusa@gmail.com (S.M.)
* Correspondence: wmasamba@wsu.ac.za
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
Academic Editor: Narciso M. Garrido
Received: 10 September 2019; Accepted: 9 October 2019; Published: 16 October 2019
ꢀꢁꢂꢃꢄꢅꢆ
Abstract: The ethylation of aryl alcohols by an ethyl moiety of boron trifluoride etherate is described.
The reaction proceeded cleanly and afforded good yields of the corresponding aryl ethyl ethers.
It tolerated the presence of functional groups such as aryl, alkyl, halogens, nitro, nitrile, and
amino. However, the presence of amino or nitro groups ortho to a hydroxyl group of an aryl
compound drastically reduced the yields of the anticipated products due to the chelation of the
aforementioned functional groups with boron trifluoride etherate. A nitrogen atom in the aromatic
ring system, as exemplified by hydroxypyridine and 8-hydroxyquinoline, completely inhibited the
reaction. Resorcinol, hydroquinone, and aryl alcohols with aldehyde functions decomposed under
the reaction conditions.
Keywords: aryl alcohols; aryl ethyl ethers; boron trifluoride etherate; ethylation; functional groups
1. Introduction
The unprecedented ethylation reaction of carboxylic acids by an ethyl moiety of boron trifluoride
etherate (BTE) to form corresponding ethyl esters in the absence of ethyl alcohol may have opened
up a new synthetic route for the formation of aryl ethyl ethers, thanks to the observed simultaneous
formation of ethyl p-ethoxybenzoate from p-hydroxybenzoic acid [1].
Aryl ethyl ethers find varied applications in industry ranging from solvents, paints, cosmetics, and
pharmaceuticals [
phenacetin [ ],
while some derivatives of aryl ethers exhibit antioxidative properties [
2
β
]. For example, p-ethoxyaniline is the precursor for the production of the analgesic
-ethoxynaphthalene (also known as nerolin) is used as a fixative in perfumery [
]. In light of the aforementioned
3,4
5]
6
properties of aryl ethyl ethers and their potential applications in the chemical and pharmaceutical
industries, we set out to explore the alkylation of various phenols using this new ethylating agent.
The traditional Williamson ether synthesis, outlined in Figure 1, involves the SN2 reaction of an
aryloxide with a primary alkyl halide, or of an EARS reaction of an alkoxide with an aryl halide [
the presence [8,9] or absence of a solvent [10].
7], in
Figure 1. Conventional Williamson ether synthesis of alkyl aryl ethers.
Though effective and generally considered to be the method of choice, the Williamson ether
synthesis suffers from some drawbacks such as the toxicity of the associated alkyl halides and
Molecules 2019, 24, 3720; doi:10.3390/molecules24203720
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dimethyl and diethyl sulfate. In addition, some alkyl halides involved in this reaction are prone to
elimination under basic reaction conditions. The Cu-promoted Ullmann ether synthesis [11] and its
variants [8,12,13] are a useful alternative method, but is limited to certain reactive substrates and only
takes place in high boiling polar solvents. The Mitsunobu protocol, whereby the relevant phenol and
alcohol are condensed in the presence of diethyl azodicarboxylate and triphenylphosphine, smoothly
allows access to the expected alkyl aryl ethers in good to excellent yields [14]. However the resultant
triphenylphosphine oxide poses tremendous challenges during product purification. Recently, an
alternative version of the Williamson ether synthesis using dialkyl carbonates and imidazole carbamates
as the alkylating agents [4,15–17] has been proposed. Because BTE is mostly used as catalyst at low
temperatures, its capacity to act as an alkylating agent has eluded the attention of organic chemists
until now. We wish to report here our findings on its high temperature reaction with variously
substituted phenols.
2. Results and Discussion
The results obtained in the reaction of various aryl alcohols with boron trifluoride etherate (BTE)
are summarized in Figure 2 below.
Various aryl alcohols were ethylated under the above reaction conditions affording the
corresponding ethers in low to excellent yield depending on the substitution on the aromatic ring.
The reaction tolerated certain substituents such as, alkyl (compounds
7–9), halogens (compounds 2, 3,
5
, and ), nitro (compound ), nitrile (compound 13) and amino (compound 10). The influence of some
6
4
substituents, such amino, hydroxyl and nitro, on the overall outcome of the reaction depended on
its nature and its position relative to the reaction center. Thus, while p-nitrophenol was converted to
p-ethoxynitrobenzene (compound 4), its ortho isomer (o-nitrophenol) failed to react under the same
reaction conditions, most likely due to the steric hindrance brought about by the proximity of the
nitro to the hydroxyl group. The amino group on the other hand showed a somewhat different trend:
p-aminophenol was ethylated, albeit in low yield (compound 10) after refluxing overnight. Its ortho
isomer (o-aminophenol), on the other hand, formed the corresponding ether only in trace amounts and
the slow reaction could also be attributed to the steric hindrance between the two adjacent groups
(amino and hydroxyl). All three isomeric hydroxyphenols led to decomposition products, forming
tarry materials. A nitrogen atom forming part of the aromatic ring system completely inhibited the
ethylation reaction as exemplified by p-hydroxypyridine and 8-hydroxyquinoline, probably due to
the chelation of the nitrogen atom onto the Lewis acid, leading to the formation of resinous materials.
The presence of a nitrile group slowed down the ethylation reaction considerably (compound 13) and
only 20% of the anticipated product was obtained after refluxing the reaction overnight. As in all
the cases where low yields are obtained, the starting material was not recovered and was completely
converted into tars. All three isomers of hydroxybenzaldehyde decomposed and formed resinous
materials. The decomposition of p-hydroxybenzyl alcohol, on the other hand, may not be surprising
given that hydroxybenzyl alcohols are prone to polymerization under acidic conditions [18].
BTE promotes the formation of a carbocation with aliphatic hydroxyl groups, which subsequently
undergo alkene formation if β-hydrogen atoms are present [19]. The alkenes formed in the process are
likely to polymerize under the above reaction condition as observed in our previous investigations
wherein undecylenic acid was esterified to ethyl undecylenate followed by the polymerization of the
double bond [1]. Although the alkylation of carboxylic acids and ethylation of phenols were carried
out in BTE as solvent, preliminary experiments done using this reagent in stoichiometric amounts
without a solvent have proved to be equally successful. In the presence of solvents such as toluene and
1,2-dichloroethane the reactions were too slow to be of any significant value. The mechanism of the
ethylation reaction is believed to involve the coordination of the oxygen atom of the hydroxyl group
with BTE, followed by the transfer of the ethyl group by alkylation as depicted in Scheme 1.

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Figure 2. Alkylation of aryl alcohols by boron trifluoride etherates. * Reflux overnight. ** Reflux of
4-phenylbutyric acid with boron trifluoride methyl etherate. *** Reflux of the aryl alcohol in boron
trifluoride methyl etherate. **** Reflux of o-iodobenzoic acid with boron trifluoride methyl etherate.
Scheme 1. Proposed alkylation mechanism.
A comparison between reported results of the synthesis of selected aryl ethyl ethers with the
results obtained in the present work is shown in Table 1. The merit of this method lies in its novelty
and simplicity, consisting merely in refluxing the substrate in BTE.

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Table 1. Comparison of the results obtained for the synthesis of aryl ethyl ethers with those recently
reported in the literature.
Product
This Work (%)
Literature Conditions
Literature Yield (%)
Reference
[4]
Phenol/EtONa/diethyl carbonate, 137
◦C/42 h.
p-Chlorophenol/K2CO3/EtBr/Acetone,
Phenetole 1
84.8
95
71
89
p-Chloroethoxybenzene 2
p-Ethoxytoluene 11
p-Nitroethoxybenzene 4
β-Ethoxynaphthalene 18
[20]
reflux, 3 h.
p-Iodotoluene/NMP, 170 ◦C/Cu2O
(5%), CsCO3 (2 eqv), MW, 30 min.
p-Fluoronitrobenzene/EtOH, Triton
B/50 ◦C, 20 h.
88
77
[21]
72
93
[22]
2-naphthol/EtBr/NaOH
85
98.1
[23]
40%/TBAB/Toluene, 70 ◦C, 4 h.
Similar reactions using boron trifluoride methyl etherate with either carboxylic acids [
phenols produced similar results (see compounds 14 15, and 17), with the only notable exception of
the reaction with 4-phenylbutyric acid, which led to the formation of -tetralone, the product of the
1] and
,
α
intramolecular Friedel-Crafts acylation in 76% yield. These results show that boron trifluoride methyl
etherate is a stronger Lewis acid than BTE.
3. Materials and Methods
General Information
Solvents (n-hexane, ethyl acetate) were purchased from Shalom Laboratory Supplies cc; TLC
plates (silica 60) were obtained from DLD Scientific SA cc; boron trifluoride etherate and boron
trifluoride dimethyl etherate were procured from Merck SA (Pty) Ltd; anhydrous sodium sulfate was
obtained from Prestige Laboratory Supplies and anhydrous calcium chloride was purchased from
United Scientific SA cc. All the above chemicals were used without further purification. Products were
characterized by 1H- and 13C-NMR spectroscopy using a Varian spectrometer at 400 and 100 MHz
for proton and carbon-13, respectively. Spectra were recorded from CDCl3 solutions employing TMS
as an internal reference. All spectra are reported as
compounds in Supplementary Materials.
δ (ppm) values. Please find the NMR spectra of
General procedure (compound
1 [4,11]): In a 50 mL round-bottomed flask equipped with a
magnetic stirring bar, a reflux condenser and a calcium chloride drying tube were placed phenol
(1 g, 10.6 mmol) an◦d boron trifluoride etherate (10 mL, 77 mmol). The reaction mixture was stirred
and heated to 120 C for four hours during which the progress of the reaction was monitored by
thin layer chromatography (n-hexane/ethyl acetate 7:1). The cooled reaction mixture was carefully
diluted with water (20 mL) and extracted with n-hexane. The aqueous phase was further extracted
with n-hexane (20 mL). The combined organic extract was washed with water (10 mL) followed by a
saturated solution of NaHCO3 (10 mL) until complete cessation of effervescence. The organic layer
was separated and dried over anhydrous Na2SO4 and concentrated in vacuo affording a clear liquid,
1.23 g (94.9%). Column chromatography on silica gel (n-hexane/ethyl acetate 7:1) gave 1.1 g (84.8%) of
1
a pleasant-smelling oil. δH (400 MHz, CDCl3): H NMR (400 MHz, Chloroform-d)
δ 7.23–7.09 (m, 2H),
6.89–6.76 (m, 3H), 3.93 (q, J = 7.0 Hz, 2H), 1.32 (t, J = 7.0, 3H); 13C NMR (101 MHz, Chloroform-d)
δ
158.93, 129.43, 120.53, 114.47, 63.27, 14.86.
Procedure for the preparation of α-tetralone (compound 16 [24]): A 50 mL round-bottomed
flask equipped with a magnetic stirring bar, a reflux condenser and a calcium chloride drying tube
was charged 4-phenylbutyric acid (1g, 6.1 mmol) and boron trifluoride dimethyl etherate (10 mL,
113 mmol). The reaction mixture was stirred and heated reflux for four hours during after which the
thin layer chromatography analysis (n-hexane/ethyl acetate 5:1) showed that the reaction was complete.
The cooled reaction mixture was carefully diluted with water (20 mL) and extracted with n-hexane.
The aqueous phase was further extracted with n-hexane (20 mL). The combined organic extract was
washed with water (10 mL) followed by a saturated solution of NaHCO3 (10 mL) until complete

Molecules 2019, 24, 3720
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cessation of effervescence. The organic layer was separated and dried over anhydrous Na2SO4 and
concentrated in vacuo affording a clear liquid which was purified by column chromatography on silica
1
gel (n-hexane/ethyl acetate 5:1) to give clear liquid (0.622 g, 76%). H NMR (400 MHz, Chloroform-d)
δ
8.00 (d, J = 7.7 Hz, 1H), 7.47–7.39 (t, J = 7.7 Hz, 1H), 7.27 (t, J = 7.7 Hz, 1H), 7.22 (d, J = 7.7 Hz, 1H), 2.93
(t, J = 6.0 Hz, 2H), 2.62 (t, J = 6.0 Hz, 2H), 2.10 (p, J = 6.4 Hz, 2H); 13C NMR (101 MHz, Chloroform-d)
δ
198.22, 144.36, 133.26, 132.47, 128.65, 126.99, 126.47, 39.02, 29.56, 23.15.
p-Ethoxychlorobenzene 2 [20]: clear liquid, 1.13 g (93%); 1H NMR (400 MHz, Chloroform-d) δ 7.17–7.08
(m, 2H), 6.75–6.67 (m, 2H), 3.88 (q, J = 7.0 Hz, 2H), 1.30 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz,
Chloroform-d) δ 157.55, 129.24, 125.31, 115.72, 63.71, 14.72.
Ethoxy-2,4-dichlorobenzene
3 [ δ 7.27 (d,
25]: clear liquid, 0.91 g (78%); 1H NMR (400 MHz, Chloroform-d)
J = 2.6 Hz, 1H), 7.07 (dd, J = 8.8, 2.6 Hz, 1H), 6.73 (d, J = 8.8 Hz, 1H), 3.98 (q, J = 7.0 Hz, 2H), 1.37 (t, J =
7.0 Hz, 3H); 13C NMR (101 MHz, Chloroform-d)
14.59.
δ 153.28, 129.89, 127.46, 125.42, 123.59, 113.96, 65.00,
p-Ethoxynitrobenzene 4 [ δ 8.18
10]: pale yellow solid, 0.87 g (72%); 1H NMR (400 MHz, Chloroform-d)
(d, J = 9.1 Hz, 2H), 6.93 (d, J = 9.1 Hz, 2H), 4.12 (q, J = 6.9 Hz, 2H), 1.45 (t, J = 7.0 Hz, 3H). 13C NMR
(101 MHz, Chloroform-d) δ 164.03, 125.92, 114.35, 64.40, 14.55.
o-Ethoxyfluorobenzene
5
[
26]: clear liquid, 0.74 g (59%); 1H NMR (400 MHz, Chloroform)
δ
6.86–7.11 (m,
4H), 4.11 (q, J = 7.0 Hz, 2H), 1.46 (t, J = 7.0 Hz, 3H);13C NMR (101 MHz, Chloroform-d)
δ
152.75 (d, JC-F
= 245.25), 146.95 (d, JC-F = 10.12), 124.20 (d, JC-F = 3.89), 120.85 (d, JC-F = 7.00), 116.08 (d, JC-F = 17.91),
114.84 (d, JC-F = 1.55), 64.80, 14.75.
1
Ethoxy-2,6-difluorobenzene
6
[
27]: clear liquid, 0.63 g (51.7%); H NMR (400 MHz, Chloroform-d)
δ
δ
6.98–6.73 (m, 3H), 4.18 (qm, J = 7.0, 2H), 1.37 (t, J = 7.0, 3H); 13C NMR (101 MHz, Chloroform-d)
156.41 (dd, JC-F = 248.34, 5.45), 135.44 (t, JC-F = 14.41), 122.60 (t, JC-F = 9.34), 112.04 (dd, JC-F = 16.35,
6.23), 64.80, 14.75.
p-Ethoxytoluene
7 [ δ 7.02–6.95 (m,
21]: clear liquid, 1.11 g (88%); 1H NMR (400 MHz, Chloroform-d)
2H), 6.75–6.67 (m, 2H), 3.91 (q, J = 7.0, 2H), 2.19 (s, 3H), 1.31 (t, J = 7.0, 3H); 13C NMR (101 MHz,
Chloroform-d) δ 156.76, 129.82, 129.64, 114.28, 63.36, 20.41, 14.85.
o-Ethoxytoluene 8 [ δ 7.56–7.46 (m, 2H),
21]: clear liquid, 0.67 g (53%); 1H NMR (400 MHz, Chloroform-d)
7.26–7.13 (m, 2H), 4.39 (q, J = 7.0 Hz, 2H), 2.61 (s, 3H), 1.79 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz,
Chloroform-d) δ 159.02, 139.40, 129.18, 121.38, 115.40, 111.38, 63.23, 21.52, 14.90.
m-Ethoxytoluene
9 [4 δ 7.19 (t, J = 8.1 Hz,
]: clear liquid, 1.13 g (90%); 1H NMR (400 MHz, Chloroform-d)
1H), 6.56–6.46 (m, 3H), 4.03 (q, J = 7.0 Hz, 2H), 3.80 (s, 3H), 1.43 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz,
Chloroform-d) δ 159.02, 139.40, 129.18, 121.38, 115.40, 111.38, 63.23, 21.52, 14.90.
p-Ethoxyaniline 10 [ δ 6.69–6.62
28]: light yellow liquid, 0. 21 g (17%); 1H NMR (400 MHz, Chloroform)
(m, 2H), 6.55 (d, J = 8.7 Hz, 2H), 3.87 (q, J = 7.0 Hz, 2H), 3.26 (bs, 2H), 1.29 (t, J = 7.0 Hz, 3H); 13C NMR
(101 MHz, Chloroform-d) δ 152.13, 139.79, 116.44, 115.67, 64.04, 14.95.
α
-Ethoxynaphthalene 11 [ δ 7.64–7.82
28]: clear liquid, 0.88 g (74%);1H NMR (400 MHz, Chloroform-d)
(m, 3H), 7.47–7.51 (m, 1H), 7.36–7.40 (m, 1H), 7.16–7.23 (m, 2H), 4.26 (q, J = 6.85 Hz, 2H), 1.64 (t, J =
6.85 Hz, 3H); 13C NMR (101 MHz, Chloroform-d)
δ 156.9, 134.59, 129.29, 128.87, 127.59, 126.67, 126.23,
123.44, 118.96, 106.51, 63.35, 14.75.
β
-Ethoxynaphthalene 12 [4, δ 8.47–8.50
23]: clear liquid, 1.01 g (85%);1H NMR (400 MHz, Chloroform-d)
(m, 1H), 7.91–7.93 (m, 1H), 7.46–7.63 (m, 4H), 6.87 (d, J = 7.83 Hz, 1H), 4.26 (q, J = 7.0 Hz, 2H), 1.64
(t, J = 7.0 Hz, 3H); 13C NMR (101 MHz, Chloroform-d)
δ 154.70, 134.47, 127.35, 126.23, 125.85, 125.70,
124.96, 122.06, 119.93, 104.51, 63.55, 14.74.

Molecules 2019, 24, 3720
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p-Ethoxybenzonitrile 13
[
29]: white solid, 0.25 g (20%); 1H NMR (400 MHz, Chloroform)
δ
7.54–7.46
(m, 2H), 6.90–6.82 (m, 2H), 4.01 (q, J = 7.0 Hz, 2H), 1.37 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz,
Chloroform-d) δ 162.23, 133.94, 119.27, 115.13, 103.69, 63.90, 14.53.
p-Chloroanisole 14
[
30]: colourless liquid, 0.82 g (75%);1H NMR (400 MHz, Chloroform)
δ
7.24 (d, J =
8.7 Hz, 2H), 6.83 (d, J = 8.7 Hz, 2H), 3.78 (s, 3H). 13C NMR (101 MHz, Chloroform-d)
δ 158.10, 129.23,
125.43, 115.06, 55.40.
p-Nitroanisole 15
[
31]: white solid, 0.88 g (80%);1H NMR (400 MHz, Chloroform)
δ
8.17 (d, J = 9.2 Hz,
2H), 6.93 (d, J = 9.2 Hz, 2H), 3.89 (s, 3H). 13C NMR (101 MHz, Chloroform-d)
δ 164.52, 141.51, 125.79,
113.84, 55.78.
1
Methyl o-iodobenzoate 17
[
32]; colorless liquid, 0.9441g (89% yield. H NMR (400 MHz, Chloroform)
δ
7.95 (d, J = 7.83 Hz, 1H), 7.76 (d, J = 7.44 Hz, 1H), 7.36 (t, J = 7.63 Hz, 1H), 3.90–7.11 (t, J = 7.44 Hz, 1H).
13C NMR (101 MHz, Chloroform-d) δ 166.80, 141.17, 134.88, 132.56, 130.82, 127.79, 94.00, 55.20.
4. Conclusions
This reaction compares more favorably in terms of cost and simplicity to other potential processes,
especially those listed in Table 1 above.
While the high cost of BTE may be a hindrance to a wide scale industrial application of this
ethylation protocol compared to the traditional Williamson ether synthesis, it may be of use in the
pharmaceutical and fine chemical industries, where batch reactions are widely in operation and
emphasis is on small production volumes.
Supplementary Materials: The NMR spectra of compounds obtained in this study are available online.
Author Contributions: Conceptualization, W.M.; methodology, W.M. and N.D.J.; experiments, Y.M., N.I.M., E.M.
and S.M.; writing-original draft preparation, W.M.; writing-review and editing, N.D.J.
Funding: This research was funded by Walter Sisulu University Directorate of Research Development
and Innovation.
Conflicts of Interest: The authors declare no conflict of interest.
References
1.
Jumbam, N.D.; Maganga, Y.; Masamba, W.; Mbunye, N.I.; Mgoqi, E.; Mtwa, S. Unprecedented alkylation of
carboxylic acids by boron trifluoride etherate. Bull. Chem. Soc. Ethiopia 2018, 32, 387–392. [CrossRef]
2.
Sutter, M.; Lafon, R.; Raoul, Y.; Métay, E.; Lemaire, M. Heterogeneous Palladium-catalyzed synthesis of
aromatic ethers by solvent-free dehydrogenative aromatization: Mechanism, scope, and limitations under
aerobic and non-aerobic conditions. Eur. J. Org. Chem. 2013, 2013, 5902–5916. [CrossRef]
Mirafzal, G.A.; Summer, J.M. Microwave irradiation reactions: Synthesis of analgesic drugs. J. Chem. Educ.
2000, 77, 356–357. [CrossRef]
Weidlich, T.; Pokorný, M.; Padeˇlková, Z.; Ru˚žicˇka, A. Aryl ethyl ethers prepared by ethylation using diethyl
carbonate. Green Chem. Lett. Rev. 2007, 1, 53–59. [CrossRef]
Kim, J.W.; Kim, D.J.; Han, J.U.; Kang, M.; Kim, J.M.; Yie, J.E. Preparation and characterization of zeolite
catalysts for etherification reaction. Catal. Today 2003, 87, 195–203. [CrossRef]
Shindo, K.; Tachibana, A.; Tanaka, A.; Toba, S.; Yuki, E.; Ozaki, T.; Kumano, T.; Nishiyama, M.; Misawa, N.;
Kuzuyama, T. Production of novel antioxidative prenyl naphthalen-ols by combinational bioconversion with
dioxygenase PhnA1A2A3A4 and prenyltransferase NphB or SCO7190. Biosci. Biotechnol. Biochem. 2011, 75,
505–510. [CrossRef]
3.
4.
5.
6.
7.
8.
9.
Malykhin, E.V.; Shteingarts, V.D. Alkoxylation of 4-chloronitrobenzene with aliphatic alcohols and glycols in
the presence of NaOH. Russ. J. Appl. Chem. 2012, 85, 1232–1238. [CrossRef]
Sun, H.; Sun, Y.; Tian, X.; Zhao, Y.; Qi, X. Nanosized ferric hydroxide catalyzed C-O cross-coupling of phenol
and halides to generate phenoxy ether. Asian J. Chem. 2013, 25, 6189–6191. [CrossRef]
Smith, R.G.; Vanterpool, A.; Kulak, H.J. Dimethyl sulfoxide as a solvent in the Williamson ether synthesis.
Can. J. Chem. 1969, 47, 2015–2020. [CrossRef]

Molecules 2019, 24, 3720
7 of 8
10. Xionga, W.; Dinga, Q.; Chena, J.; Dinga, J.; Wua, H. Solvent-free synthesis of aryl ethers promoted by
tetrabutylammonium fluoride. J. Chem. Res. 2010, 34, 395–398. [CrossRef]
11. Keegstra, M.A.; Peters, T.H.; Brandsma, L. Copper (I) halide catalysed synthesis of alkyl aryl and alkyl
heteroaryl ethers. Tetrahedron 1992, 48, 3633–3652. [CrossRef]
12. Milton, E.J.; Fuentes, J.A.; Clarke, M.L. Palladium-catalysed synthesis of aryl-alkyl ethers using alkoxysilanes
as nucleophiles. Org. Biomol. Chem. 2009, 7, 2645–2648. [CrossRef] [PubMed]
13. Paul, S.; Gupta, M. Zinc-catalyzed Williamson ether synthesis in the absence of base. Tetrahedron Lett. 2004
45, 8825–8829. [CrossRef]
,
14. Manhas, M.S.; Hoffman, W.; Lal, B.; Bose, A.K. Steroids. Part X. A convenient synthesis of alkyl aryl ethers. J.
Chem. Soc. Perk. Trans. 1 1975, 5, 461–463. [CrossRef]
15. Guerrero, L.R.; Rivero, I.A. 1,2-Dimethylimidazole (DMI) and microwaves in the alkylation of carboxylic
acids and phenols with dimethyl and diethyl carbonates. Arkivoc 2008, 11, 295–306.
16. Kreye, O.; Over, L.C.; Nitsche, T.; Lange, R.Z.; Meier, M.A.R. Organic carbonates: Sustainable and
environmentally-friendly ethylation, allylation, and benzylation reagents. Tetrahedron 2015, 71, 293–300.
[CrossRef]
17. Heller, S.T.; Sarpong, R. On the reactivity of imidazole carbamates and ureas and their use as esterification
and amidation reagents. Tetrahedron 2011, 67, 8851–8859. [CrossRef]
18. Kobayashi, A.; Konishi, G.-I. Rapid synthesis of phenolic resins by microwave-assisted self-condensation of
hydroxybenzyl alcohol derivatives. Polym. J. 2008, 40, 590–591. [CrossRef]
19. Posner, G.H.; Shulman-Roskes, E.M.; Oh, C.H.; Carry, J.-C.; Green, J.V.; Clark, A.B.; Dai, H.; Anjeh, T.E.N.
BF3 OEt2 promotes fast, mild, clean and regioselective dehydration of tertiary alcohols. Tetrahedron Lett.
·
1991, 32, 6489–6492. [CrossRef]
20. Bouider, N.; Fhayli, W.; Ghandour, Z.; Boyer, M.; Harrouche, K.; Florence, X.; Pirotte, B.; Lebrun, P.; Faury, G.;
Khelili, S. Design and synthesis of new potassium channel activators derived from the ring opening of
diazoxide: Study of their vasodilatory effect, stimulation of elastin synthesis and inhibitory effect on insulin
release. Bioorg. Med. Chem. 2015, 23, 1735–1746. [CrossRef]
21. Mehmood, A.; Devine, W.G.; Leadbeater, N.E. Development of methodologies for copper-catalyzed C–O
bond formation and direct cyanation of aryl iodides. Top. Catal. 2010, 53, 1073–1080. [CrossRef]
22. Meshram, H.M.; Goud, P.R.; Reddy, B.C.; Kumar, D.A. Triton B–Mediated Efficient and Convenient
Alkoxylation of Activated Aryl and Heteroaryl Halides. Synth. Commun. 2010, 40, 2122–2129. [CrossRef]
23. Mathew, S.H.; Haridas, K.R. Synthesis and properties of N,N,N0-tris-(2-ethoxy-naphthalenen-1-yl)–N,N,N0
triphenylbenzene 1, 3, 5-triamine for dye sensitized solar cell. Bull. Mater. Sci. 2012, 35, 123–127. [CrossRef]
24. Tang, G.; Gong, Z.; Han, W.; Sun, X. Visible light mediated aerobic photocatalytic activation of CH bond by
riboflavin tetraacetate and N-hydroxysuccinimide. Tetrahedron Lett. 2018, 59, 658–662. [CrossRef]
25. Foglia, T.A.; Swern, D. Reaction of N,N-dichlorourethan with ethers. A novel cleavage-chlorination reaction.
Tetrahedron Lett. 1967, 8, 3963–3967. [CrossRef]
26. Dubbaka, S.R.; Narreddula, V.R.; Gadde, S.; Mathew, T. Silver-mediated fluorination of potassium
aryltrifluoroborates with Selectfluor®. Tetrahedron 2014, 70, 9676–9681. [CrossRef]
27. Yunlong, J.; Yuan, Y.; Jin, D. Method for preparing difluoro alkyl ether benzene. U.S. Patent No. CN101003468
(A), 25 July 2007.
28. Kumar, A.; Kumar, P.; Paul, S.; Jain, S.L. Visible light assisted reduction of nitrobenzenes using Fe(bpy)3+2/rGO
nanocomposite as photocatalyst. Appl. Surf. Sci. 2016, 386, 103–114. [CrossRef]
29. Xu, B.; Jiang, Q.; Zhao, A.; Jia, J.; Liu, Q.; Luo, W.; Guo, C. Copper-catalyzed aerobic conversion of the C=O
bond of ketones to a C
11264–11267. [CrossRef]
≡N bond using ammonium salts as the nitrogen source. Chem. Commun. 2015, 51,
30. Lui, M.Y.; Yuen, A.K.L.; Masters, A.F.; Maschmeyer, T. Masked N-heterocyclic carbene-catalyzed alkylation
of phenols with organic carbonates. ChemSusChem 2016, 9, 2312–2316. [CrossRef]
31. Maleki, A.; Aghaei, M.; Paydar, R. Highly efficient protocol for the aromatic compounds nitration catalyzed
by magnetically recyclable core/shell nanocomposite. J. Iran. Chem. Soc. 2017, 14, 485–490. [CrossRef]
32. Curti, F.; Tiecco, M.; Pirovano, V.; Germani, R.; Caselli, A.; Rossi, E.; Abbiati, G. p-TSA-Based DESs as “Active
Green Solvents” for Microwave Enhanced Cyclization of 2-Alkynyl-(hetero)-arylcarboxylates: An alternative
access to 6-substituted 3,4-fused 2-pyranones. Eur. J. Org. Chem. 2019, 2019, 1904–1914. [CrossRef]

Molecules 2019, 24, 3720
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Sample Availability: Samples of the compounds 1–17 are available from the authors.
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