A novel route to the synthesis of α,Ω-diphenylalkanes

Article abstract of DOI:10.3184/174751917X15009724013088

A novel route to the synthesis of α,ω-diphenylalkanes is reported. Toluene was metalated in the benzylic position by n-butyllithium with THF as an activating reagent, and then directly reacted with α,ω-dichloroalkanes to obtain the target product. This process provides a facile and efficient route to the synthesis of α,Ω-diphenylalkanes.

Full text of DOI:10.3184/174751917X15009724013088

JOURNAL OF CHEMICAL RESEARCH 2017
VOL. 41 AUGUST, 473–474
RESEARCH PAPER 473
A novel route to the synthesis of α,ω-diphenylalkanes
Hui Chena*, Yancai Chena,b, Yinlong Zhanga, Zhenqiang Yanga, Ji Lia,b, Ruina Yanga and Wenxin Wanga
aInstitute of Chemistry, Henan Academy of Sciences, Zhengzhou 450002, P.R. China;
bCollege of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, P.R. China
A novel route to the synthesis of α,ω-diphenylalkanes is reported. Toluene was metalated in the benzylic position by n-butyllithium with
THF as an activating reagent, and then directly reacted with α,ω-dichloroalkanes to obtain the target product. This process provides a
facile and efficient route to the synthesis of α,ω-diphenylalkanes.
Keywords: α,ω-diphenylalkane, toluene, benzylic metalation, tetrahydrofuran, α,ω-dichloroalkane
Recently, α,ω-diphenylalkanes have attracted attention because
of their promising applications in the field of fluorescent
probes.1–3 They are also in demand as ligands for metal
complexes,4 as precursors for cyclophanes/calixarenes5 and as
polymerisation initiators6. In addition, α,ω-diphenylalkanes
are important reagents for improving the viscosity index of
lubricants, especially in high-temperature nuclear-radiation-
resistant hydraulic fluids.7
Synthetic procedures to produce α,ω-diphenylalkanes
have been described previously. For example, the preparation
of α,ω-diphenylalkanes has been reported8 by the Friedel–
Crafts acylation of arenes using ClOC(CH2)nCOCl in the
presence of Lewis acid with a subsequent reduction. As
another approach to the α,ω-diphenylalkanes, the coupling of
Grignard reagents with α,ω-dihaloalkanes using a transition
metal catalyst has been thoroughly studied.9 Reduction of the
corresponding ketones and α,β-enones is also a powerful way
to obtain α,ω-diphenylalkanes.10 Iridium-catalysed reactions
of ω-phenylalkanols to form α,ω-diphenylalkanes have been
reported recently.11 However, these previous methods have
some major drawbacks including multistep reactions, harsh
reaction conditions, and/or the use of transition metal catalysts.
The development of a facile, versatile, and waste-minimising
method for preparing α,ω-diphenylalkanes from easily
accessible chemicals is highly desirable.
firstly metalated in the benzylic position by n-BuLi in hexane,
and then CH2Cl2 was added to produce 1a. Different activating
reagents such as Et2O, THF and tetramethylethylenediamine
(TMEDA) were employed to evaluate the solvent effect under
similar reaction conditions (Table 1). When no activating
reagent was used in the reaction system, the reaction did not
occur, which indicated that toluene was not activated by n-BuLi
in hexane at room temperature. When Et2O, THF were used,
1,3-diphenylpropane 1a was generated in moderate yield. THF
gave the best result (62% yield). However, when TMEDA as
the traditional depolymersation reagent for n-BuLi was added,
the yield was very low. The yield was also low when TMEDA
was used in conjunction with Et2O and THF. We considered
that the low yield of 1a may be caused by the high activity of
the benzyl lithium intermediate, and hence the mild THF gave
better results when reacted with CH2Cl2.
The promising outcome of the initial screening encouraged
us to extend the observed amplification to a series of
diphenylalkanes 1b–d, and each gave satisfactory results.
Along with increase of the alkyl chain of α,ω-dichloroalkanes,
the yields of 1b–d were increased from 67% to 78%. This
result indicated that a decrease in steric hindrance was more
favourable for the reaction.
Under the optimal experimental conditions, different α,ω-
dibromoalkanes were also used to see if similar results were
obtained (Scheme 2). It was surprising to find that α,ω-
dibromoalkanes gave completely different results. When CH2Br2
was employed instead of CH2Cl2, only a trace of 1a (1%) was
In this paper, we report a novel synthetic method for
producing α,ω-diphenylalkanes. At room temperature, toluene
was metalated in the benzylic position by n-butyllithium
with THF as an activating reagent, and then directly reacted
with α,ω-dichloroalkanes to obtain the target products. To
our knowledge, this has not been attempted previously. This
reaction provides a simple and clean route to synthesis of
α,ω-diphenylalkanes from easily available materials. α,ω-
Diphenylalkanes 1a–d, which contain different alkyl chains,
were synthesised as shown in Scheme 1.
Table 1 The effect of reaction conditions on the yield of compound 1a
Entry
Activating reagent
0
Et2O
THF
TMEDA
Yield of 1a（%）
1
2
3
4
5
6
0
51
62
23
47
18
Results and discussion
Et2O +TMEDA
THF +TMEDA
A series of experiments were carried out to optimise the
reaction conditions. When we started our work, toluene was
Me
Li
CH2
Cl
Cl
n-BuLi
THF
n
n
1a-d
n = 1, 2, 3, 4
Scheme 1
* Correspondent. E-mail: hchen@kingorgchem.com

474 JOURNAL OF CHEMICAL RESEARCH 2017
Me
CH2Li
n-BuLi
THF
+
+
BrCH2Br
Br
20%
5%
1%
BrCH2CH2Br
7
0
%
Scheme 2
1,5-Diphenylpentane (1c):15 Colourless oil; 75% yield; 1H NMR (400
MHz, CDCl3) δ 1.35–1.45 (m, 2H), 1.61–1.70 (m, 4H), 2.58–2.63 (t,
J = 8.0 Hz, 4H), ,7.15–7.20 (m, 6H), 7.25–7.31 (m, 4H); MS (ESI) m/z:
225.1646 [M + H]+; Anal. calcd for C17H20: C, 91.01; H, 8.99; found: C,
91.02; H, 8.98%.
detected. It was accompanied by 20% of 1,2-diphenylethane
and 5% of 2-bromoethylbenzene. When 1,2-dibromoethane
was used, only 1,2-diphenylethane 1e was obtained in relatively
higher yield (70% yield). This suggested that here α,ω-
dibromoalkane mainly played the role of oxidant.12
1,6-Diphenylhexane (1d):16 Colourless oil; 78% yield; 1H NMR (400
MHz, CDCl3) δ 1.33–1.49 (m, 4H), 1.60–1.71 (m, 4H), 2.58–2.69 (t,
J = 8.0 Hz, 4H), 7.17–7.23 (m, 5H), 7.24–7.35 (m, 5H); MS (ESI) m/z:
239.1798 [M + H]+; Anal. calcd for C18H22: C, 90.70; H, 9.30; found: C,
90.71; H, 9.29%.
Conclusion
In summary, we have discovered a facile and efficient manner
to synthesise α,ω-diphenylalkanes from toluene as a starting
material. Regioselective metalation in the benzylic position
with n-BuLi in THF could be used in conjunction with α,ω-
dichloroalkaneto allow directaccess to the α,ω-diphenylalkanes
in moderate yield. This one-pot synthetic operation did not
require additional synthetic steps to preactivate the coupling
partners or the use of transition metal catalysts. Moreover,
the convenience and low costs associated with the process are
worth highlighting.
1,2-Diphenylethane (1e):17 White solid; 70% yield; m.p. 51.8–53.5
1
°C; H NMR (400 MHz, CDCl3) δ 2.99 (s, 4H), 7.22–7.30 (m, 6H),
7.35–7.40 (m, 4H); MS (ESI) m/z: 183.1172 [M + H]+; Anal. calcd for
C14H14: C, 92.26; H, 7.74; found: C, 92.25; H, 7.75%.
Acknowledgements
We thank the Natural Science Foundation of China (Project No.
21502045) and Outstanding Youth Foundation for Scientific and
Technological Innovation of Henan Province (174100510018)
for the financial support.
Experimental
All experiments were performed under a dry argon atmosphere
using standard Schlenk techniques. Column chromatography was
performed in air, unless stated in text. All solvents and reagents were
of reagent quality, purchased from commercial sources and used
without further purification. Toluene, Et2O, and THF were dried and
distilled from sodium/benzophenone just before use. 1H NMR spectra
Received 2 May 2017; accepted 14 July 2017
Paper 1704738
https://doi.org/10.3184/174751917X15009724013088
Published online: 31 July 2017
1
were recorded on Bruker AM400. H chemical shifts were reported
in parts per million (ppm) relative to Si(CH3)4 as external standard.
High-resolution mass spectra were obtained on a Varian MAT 311
instrument. Elemental analysis was performed on a Carlo-Erba-1106
autoanalyser.
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