Synthesis of benzyl esters from the commercially available alcohols catalyzed by TBAI via C(sp3)-H bond functionalization

Article abstract of DOI:10.1039/c6ra26387a

A direct esterification of alcohols catalyzed by TBAI via C(sp³)-H bond functionalization was achieved under mild and clean conditions. A series of benzyl esters were obtained in good to excellent yields via the C(sp³)-H bond functionalization of alkyl-substituted azaarenes.

Full text of DOI:10.1039/c6ra26387a

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Synthesis of benzyl esters from the commercially
available alcohols catalyzed by TBAI via C(sp3)–H
bond functionalization†
Cite this: RSC Adv., 2017, 7, 3780
*
Dao-Qing Dong, Hui Zhang and Zu-Li Wang
Received 6th November 2016
Accepted 19th December 2016
A direct esterification of alcohols catalyzed by TBAI via C(sp3)–H bond functionalization was achieved under
mild and clean conditions. A series of benzyl esters were obtained in good to excellent yields via the C(sp3)–
H bond functionalization of alkyl-substituted azaarenes.
DOI: 10.1039/c6ra26387a
www.rsc.org/advances
Alkyl-substituted azaarenes, as key structural skeletal frame- with 2-methylquinoline (2a). As shown in Table 1, when H2O2
works of many natural products and pharmaceuticals, have was chosen as the oxidant for the model reaction, only a 20%
attracted considerable interest because of their important bio- yield of the desired product was achieved (Table 1, entry 1).
logically active properties.1 One of the most efficient methods Although O2 was also used as the oxidant for this reaction, the
for preparing alkyl-substituted azaarenes is direct C(sp3)–H yield of the product was very low (Table 1, entry 2). However, the
functionalization of the alkyl-substituted azaarenes. For model reaction smoothly proceeded in the presence of tert-butyl
example, the direct addition of C(sp3)–H bond of the alkyl- hydroperoxide (TBHP) and the corresponding product was iso-
substituted azaarenes to the unsaturated chemical bonds was lated in 86% yield (Table 1, entry 3). With respect to the catalyst,
rst independently realized in 2010 by Huang and co-workers.2f a very low yield of ester 3a was formed when TBAI was replaced
At present, esterication catalyzed by transition metals,2 by KI, I2O5, or I2 (Table 1, entry 4–6). The effect of the solvent on
Bronsted acids,3 and microwave4 has been explored. Even in the model reaction was also investigated and it was found that
some cases, these reactions can also be realized without any water was the most effective solvent. Moreover, a lower yield was
catalyst.4d,e However, versatile and practical methods for the observed when the reaction was conducted in methanol (Table
synthesis of alkyl-substituted azaarenes are still desirable.
1, entry 7) or acetonitrile (Table 1, entry 8). The optimized
On the other hand, Bu4NI has received extensive attention in reaction conditions for the model reaction were TBAI (20 mol%)
ꢀ
organic synthesis because it can overcome the drawbacks of the and TBHP (5.0 equiv.) in water at 90 C for 12 h.
expensive, poisonous, and air-sensitive properties of metals or
organometallics.5 In the presence of an oxidant (H2O2, tBuOOH,
etc.), Bu4NI has been explored as an efficient catalyst for the
Table 1 Acyloxylation of 2-methylquinoline with phenylmethanola
formation of C–O,6 C–N,7 and C–C8 bonds. For example, the
synthesis of a-ketoamides promoted by TBHP/I2 was described
by the Wang group.9 In 2014, Wan and his co-workers reported
the synthesis of substituted pyrazoles using TBAI as a catalyst
and TBHP as an oxidant.10 Tetrabutylammonium iodide-
catalyzed phosphorylation of benzyl C–H bonds via a cross-
Entry
Catalyst
Oxidant
Yield (%)
dehydrogenative coupling (CDC) reaction was also realized by
the Tang group.11 In line with our interest in green chemistry,12
herein, we report a TBAI/TBHP-promoted synthesis of benzyl
esters from the commercially available alcohols via C(sp3)–H
bond functionalization under mild reaction conditions.
At the beginning of our investigation, optimization of the
reaction conditions was focused on a variety of reaction
parameters using the model reaction of phenylmethanol (1a)
1
2
3
4
TBAI
TBAI
TBAI
KI
H2O2
O2
20
Trace
86
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
16
5
I2
Trace
Trace
30
6
I2O5
TBAI
TBAI
7b
8c
7
a
Reaction conditions: 1a (1.0 mmol), 2a (0.5 mmol), catalyst (0.2
mmol), oxidant (4.0 mmol), water (2 mL), 90 ꢀC and 12 h; isolated
yield. CH3CN was used as the solvent. CH3OH was used as the
solvent.
College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University,
Qingdao, 266109, P. R. China. E-mail: wangzulichem@163.com
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c6ra26387a
b
c
3780 | RSC Adv., 2017, 7, 3780–3782
This journal is © The Royal Society of Chemistry 2017

View Article Online
Paper
With the optimized reaction conditions in hand, the scope of
RSC Advances
the substituted alkyl azaarenes and alcohols was investigated.
The results are shown in Table 2. A variety of benzyl alcohols
bearing substituents on the benzene ring were examined for the
synthesis of benzyl esters via the C(sp3)–H bond functionaliza-
tion of 2-alkyl-substituted azaarenes.
The results indicated that a variety of functional groups,
including electron-donating (Table 2, 3g, 3e, 3t, and 3v) and
electron-withdrawing (Table 2, 3b, 3c, 3h, 3i, 3j, 3k, and 3l)
groups were tolerated and the reactions produced the corre-
sponding products in good to excellent yields (Table 2, 3a–w).
Note that 2-naphthalene methanol, 1-naphthalene methanol,
and 2-thiophenemethanol also smoothly reacted to generate
their corresponding products in 70–95% yield (Table 2, 3m, 3n,
3o, and 3s). The present reaction conditions were also suitable
for the reaction of benzyl alcohols with other alkyl-substituted
azaarenes. Various functional groups, such as uoro, chloro,
bromo, and methyl (Table 2, 3d, 3g, 3r, and 3u) were well
tolerated under the reaction conditions. Finally, the reaction of
2-methylquinoxaline with phenylmethanol generated the
desired product in 68% yield (Table 2, 3w).
Scheme 1 Proposed mechanism.
According to a report,5 a plausible mechanism was proposed
for this reaction (Scheme 1). The rst step involves the reaction
between TBHP and TBAI to generate the intermediate ammo-
nium hypoiodite 6 or iodite 7. Then, hypoiodite 6 or iodite 7
induces the production of benzyl radical 9 via the homolysis of
a benzyl C–H bond. The benzyl radical could be further oxidized
to the benzyl cation 10. Moreover, the oxidation of phenyl-
methanol 2 by TBHP occurred to form benzoic acid 3; aer
deprotonation, the benzoate anion 4 reacts with the benzyl
cation 10 to provide the nal product.
Table 2 Esterification of 2-methyl azaarenes with various alcoholsa
In summary, a direct synthetic method for the preparation of
benzyl esters via TBAI-catalyzed C(sp3)–H bond functionaliza-
tion has been reported. The reactions generate the corre-
sponding products in good yields in most of the cases under
simple and mild reaction conditions. This organic TBAI-
catalyzed one-step reaction provides a new synthetic protocol
for the synthesis of 2-alkyl azaarene derivatives. Further inves-
tigations on the detailed reaction mechanism and application
of this methodology are in progress.
Acknowledgements
Financial support from the National Natural Science Founda-
tion of China (21402103), the China Postdoctoral Science
Foundation (150030), the Scientic Research Foundation of
Shandong Province Outstanding Young Scientist Award
(BS2013YY024), and the Research Fund of Qingdao Agricultural
University's High-level Person (631303) are gratefully
acknowledged.
Notes and references
1 (a) M. C. Bagley, C. Glover and E. A. Merritt, Synlett, 2007,
2459; (b) G. D. Henry, Tetrahedron, 2004, 60, 6043; (c)
J. P. Michael, Nat. Prod. Rep., 2005, 22, 627; (d)
P. N. W. Baxter, J. M. Lehn, J. Fischerand and
M. T. Youinou, Angew. Chem., Int. Ed. Engl., 1994, 33, 2284;
(e) J. M. Lehn, Science, 2002, 295, 2400; (f) D. Henry,
Tetrahedron, 2004, 60, 6043; (g) J. P. Michael, Nat. Prod.
a
Reaction conditions: alcohol (1.0 mmol), 2-alkyl azaarene (0.5 mmol),
catalyst (0.2 mmol), oxidant (4.0 mmol), water (2 mL), 90 ꢀC and 12 h;
isolated yield.
This journal is © The Royal Society of Chemistry 2017
RSC Adv., 2017, 7, 3780–3782 | 3781

View Article Online
RSC Advances
Paper
Rep., 2005, 22, 627; (h) M. C. Bagley, C. Gloverand and
E. A. Merritt, Synlett, 2007, 2459.
Synthesis, 1972, 1; (j) J. Eames and M. Watkinson, Angew.
Chem., Int. Ed., 2001, 40, 3567; (k) M. B. Andrus and
J. C. Lashley, Tetrahedron, 2002, 58, 845; (l) L. V. Desai,
H. A. Malik and M. S. Sanford, Org. Lett., 2006, 8, 1141; (m)
2 (a) J.-J. Jin, H.-Y. Niu, G.-R. Qu, H. M. Guo and J. S. Fossey,
RSC Adv., 2012, 2, 5968; (b) H. Komai, T. Yishino,
S. Matsunaga and M. Kanai, Org. Lett., 2011, 13, 1706; (c)
B. Qian, S. Guo, C. Xia and H. Huang, Adv. Synth. Catal.,
2010, 352, 3195; (d) B. Qian, P. Xie, Y. Xie and H. Huang,
Org. Lett., 2011, 13, 2580; (e) V. B. Graves and A. Shaikh,
Tetrahedron Lett., 2013, 54, 695; (f) B. Qian, S. Guo, J. Shao,
Q. Zhu, L. Yang, C. Xia and H. J. Huang, J. Am. Chem. Soc.,
2010, 132, 3650; (g) B. Qian, D. J. Shi, L. Yang and
H. Huang, Adv. Synth. Catal., 2012, 354, 2146; (h) B. Qian,
L. Yang and H. Huang, Tetrahedron Lett., 2013, 54, 711; (i)
J. Y. Liu, H. Y. Niu, S. Wu, G. R. Qu and H. M. Guo, Chem.
Commun., 2012, 48, 9723; (j) Y. Yan, K. Xu, Y. Fang and
Z. J. Wang, J. Org. Chem., 2011, 76, 6849; (k) M. Rueping
and N. Tolstoluzhsky, Org. Lett., 2011, 13, 1095; (l)
A. Kumar, P. L. Gupta and M. Kumar, RSC Adv., 2013, 3,
18771.
3 (a) F. F. Wang, C.-P. Luo, Y. Wang, G. Deng and L. Yang, Org.
Biomol. Chem., 2012, 10, 8605; (b) R. Niu, J. Xiao, T. Liang and
X. Li, Org. Lett., 2012, 14, 676; (c) S. V. N. Vuppalapati and
Y. R. Lee, Tetrahedron, 2012, 68, 8286; (d) X. Gao, F. Zhang,
G. Deng and L. Yang, Org. Lett., 2014, 16, 3664; (e)
S. A. R. Mulla, M. Y. Pathan and S. S. Chavan, RSC Adv.,
2013, 3, 20281; (f) M. Raghua, M. Rajasekhar,
B. C. O. Reddy, C. S. Reddy and B. V. S. Reddy, Tetrahedron
Lett., 2013, 54, 3503.
¨
B. Lucke, K. V. Narayana, A. Martin and K. Jahnisch, Adv.
Synth. Catal., 2004, 346, 1407; (n) J. Zhang, E. Khaskin,
N. P. Anderson, P. Y. Zavalij and A. N. Vedernikov, Chem.
Commun., 2008, 3625; (o) J. Huang, L.-T. Li, H.-Y. Li,
E. Husan, P. Wang and B. Wang, Chem. Commun., 2012,
48, 10204; (p) L. Liu, L. Yun, Z. Wang, X. Fu and C. Yan,
Tetrahedron Lett., 2013, 54, 5383; (q) Q. Wang, J. Feng,
W. Chai, H. Geng, M. Xu, K. Wang, C. Xu, R. Fu and
R. Yuan, Tetrahedron Lett., 2014, 55, 4785; (r) J. Feng,
S. Liang, S. Chen, J. Zhang, S. Fu and X. Yu, Adv. Synth.
Catal., 2012, 354, 1287.
6 (a) L. Chen, E. Shi, Z. Liu, S. Chen, W. Wei, H. Li, K. Xu and
X. Wan, Chem.–Eur. J., 2011, 17, 4085; (b) W. Wei, C. Zhang,
Y. Xu and X. Wan, Chem. Commun., 2011, 10827; (c) B. Tan,
N. Toda and C. F. Barbas III, Angew. Chem., Int. Ed., 2012,
51, 12538.
7 (a) C. Zhu and Y. Wei, ChemSusChem, 2011, 4, 1082; (b)
T. Froehr, C. P. Sindlinger, U. Kloeckner, P. Finkbeiner and
B. J. Nachtsheim, Org. Lett., 2011, 13, 3754; (c) L. Ma,
X. Wang, W. Yu and B. Han, Chem. Commun., 2011, 11333;
(d)
U.
Kloeckner,
N.
M.
Weckenmann
and
B. J. Nachtsheim, Synlett, 2012, 23, 97; (e) S. Chen, Y. Xu
and X. Wan, Org. Lett., 2011, 13, 6152; (f) J. Xie, H. Jiang,
Y. Cheng and C. Zhu, Chem. Commun., 2012, 979; (g)
Z. Liu, J. Zhang, S. Chen, E. Shi, Y. Xu and X. Wan, Angew.
Chem., Int. Ed., 2012, 51, 3231; (h) W. Mai, H. Wang, Z. Li,
J. Yuan, Y. Xiao, L. Yang, P. Mao and L. Qu, Chem.
Commun., 2012, 10117; (i) H. Li, J. Xie, Q. Xue, Y. Cheng
and C. Zhu, Tetrahedron Lett., 2012, 53, 6479.
4 (a) N. N. Rao and H. M. Meshram, Tetrahedron Lett., 2013, 54,
5087; (b) N. N. Rao and H. M. Meshram, Tetrahedron Lett.,
2013, 54, 1315; (c) H. M. Meshram, N. N. Rao, L. C. Rao
and N. S. Kumar, Tetrahedron Lett., 2012, 53, 3963; (d)
H. Y. Li, L. J. Xing, T. Xu, P. Wang, R. H. Liu and B. Wang,
Tetrahedron Lett., 2013, 54, 858; (e) Y. Yan, K. Xu, Y. Fang
and Z. J. Wang, J. Org. Chem., 2011, 76, 6849.
´
8 (a) A. Rodrıguez and W. J. Moran, Org. Lett., 2011, 13, 2220;
(b) L. Li, J. Huang, H. Li, L. Wen, P. Wang and B. Wang,
Chem. Commun., 2012, 5187.
9 X.-B. Zhang and L. Wang, Green Chem., 2012, 14, 2141.
5 For selected examples, see: (a) R. D. Richardson and
T. Wirth, Angew. Chem., Int. Ed., 2006, 45, 4402; Angew.
Chem., 2006, 11, 4510; (b) V. V. Zhdankin and P. J. Stang, 10 J. Zhang, Y. Shao, H.-X. Wang, Q. Luo, J.-J. Chen, D.-M. Xu
Chem. Rev., 2008, 108, 5299; (c) M. Uyanik and K. Ishihara, and X.-B. Wan, Org. Lett., 2014, 16, 3312.
ChemCatChem., 2012, 4, 177; (d) A. Parra and S. Reboredo, 11 J. Xu, P.-B. Zhang, X.-Q. Li, Y.-Z. Gao, J. Wu, G. Tang and
Chem.–Eur. J., 2013, 19, 17244; (e) R. Samanta, K. Matcha Y.-F. Zhao, Adv. Synth. Catal., 2014, 356, 3331.
and A. P. Antonchick, Eur. J. Org. Chem., 2013, 5769; (f) 12 (a) Z.-L. Wang, RSC Adv., 2015, 5, 5563; (b) S.-H. Hao,
D.-Q. Dong, S.-H. Hao, Z.-L. Wang and C. Chen, Org.
Biomol. Chem., 2014, 12, 4278; (g) X.-F. Wu, J.-L. Gong and
X. Qi, Org. Biomol. Chem., 2014, 12, 5807; (h)
M. S. Kharasch and G. J. Sosnovsky, J. Am. Chem. Soc.,
1958, 80, 756; (i) D. J. Rawlinson and G. Sosnovsky,
X.-Y. Zhang, D.-Q. Dong and Z.-L. Wang, Chin. Chem. Lett.,
2015, 26, 599; (c) X.-Y. Zhang, D.-Q. Dong, T. Yue,
S.-H. Hao and Z.-L. Wang, Tetrahedron Lett., 2014, 55,
5462; (d) Z.-L. Wang, L. Wang and J.-C. Yan, Synthesis,
2009, 3744.
3782 | RSC Adv., 2017, 7, 3780–3782
This journal is © The Royal Society of Chemistry 2017