Molybdenum (VI)-catalyzed dehydrative construction of C[sbnd]O and C[sbnd]S bonds formation via etherification and thioetherification of alcohols and thiols

Article abstract of DOI:10.1016/j.mcat.2020.110954

An inexpensive, easily available, environmentally benign, and efficient catalyst molybdenum(VI) dioxo (acetylacetonate)₂ was used for the direct oxo- and thioetherification of alcohol. This method endures selective molybdenum catalyzed dehydrative synthesis of symmetrical ethers from benzylic secondary alcohols as well as unsymmetrical ethers from the reaction of benzylic secondary alcohols with primary alcohol. Furthermore, we have been also successful in the synthesis of Aryl thioether by using alcohol and thiols.

Full text of DOI:10.1016/j.mcat.2020.110954

MolecularCatalysis492(2020)110954
Contents lists available at ScienceDirect
Molecular Catalysis
journal homepage: www.elsevier.com/locate/mcat
Molybdenum (VI)-catalyzed dehydrative construction of CeO and CeS
bonds formation via etherification and thioetherification of alcohols and
thiols
Rahulkumar Rajmani Singh, Alex Whittington, Radhey S. Srivastava*
University of Louisiana at Lafayette, Department of Chemistry, Louisiana, LA 70504, USA
A R T I C L E I N F O
A B S T R A C T
Keywords:
An inexpensive, easily available, environmentally benign, and efficient catalyst molybdenum(VI) dioxo (acet-
ylacetonate)2 was used for the direct oxo- and thioetherification of alcohol. This method endures selective
molybdenum catalyzed dehydrative synthesis of symmetrical ethers from benzylic secondary alcohols as well as
unsymmetrical ethers from the reaction of benzylic secondary alcohols with primary alcohol. Furthermore, we
have been also successful in the synthesis of Aryl thioether by using alcohol and thiols.
Hydroxyl activation
Etherification
Mo catalysis
CeO and CeS bond
Dehydrative
Introduction
Construction of CeO and CeS bonds by means of substitution of the
highly deactivated hydroxyl group of alcohol have found great atten-
The formation of CeO bonds by alkylation and arylation reactions is
very important to synthesize ethers and has become a major objective
for the construction of pharmaceutically important compounds. The
common structural motif of ethers found widespread application in the
various synthesis, the common application as solvents on a daily basis.
In addition, ethers have numerous important applications such as drug
intermediates, fragrances, herbicides, plasticizers, disinfectants, and
precursors in polymers [1]. The traditional method for etherification
employs alkyl halides and sodium alkoxide, invented by Williamson
[2]. This method is not very efficient as it involved a multistep process
that requires preparation of toxic halide precursor which can be formed
from the corresponding alcohols. Another serious limitation of the
Williamson method is producing symmetrical and unsymmetrical ethers
by generating inorganic waste [3]. The formation of CeS bonds have
been exploited as an important building block for the efficient pre-
paration of naturally occurring products and range of application in
pharmaceuticals, biologically active compounds and in agrochemicals
[3a−3b]. Nevertheless, like oxo ether, thioethers also can be con-
ventionally synthesized from alkyl halide precursor involving multistep
procedures with limited substrate scope [4]. Therefore development of
a greener method which reduces the inorganic waste formation was
really important aspects of the researcher around the world.
tion in the past [5,6]. The poor ability of hydroxyl functionality as a
leaving group makes exciting to activate hydroxide. Subsequently, hy-
droxide activation by nucleophilic substitution has been recognized as a
key area for green chemistry research (Scheme 1). Dehydration trans-
formation of alcohol into valuable final products have found wide-
spread attention in organic synthesis.
These inadequacies were addressed by the development of the
transition-metal-catalyzed synthesis of ethers from diverse functional
groups. For instance, previously reported reaction for the synthesis of
Aryl ethers derivatives using aryl halides precursors and alcohols in the
reaction of Ullmann-type [7] with Pd- and Cu-catalysts, etherification
reaction of Mitsunobu-type [8], reductive deoxygenations of esters [6],
redox condensation of alcohols via alkoxydiphenylphosphines [7],
various alkenes affording corresponding ethers by hydro-etherification
reaction consuming alcohols [9], and aryl CeH bonds oxidative
etherification are reported [10]. The results of these reactions suffer
from the narrow scope and poor atom economy. Therefore, the devel-
opment of etherification reaction with direct coupling of alcohol is
essential which can be atom economical and environmentally com-
passionate and producing water as the sole byproduct (Scheme 2).
Heterogeneous acid or strong Brønsted acid catalysts have been used for
the synthesis of ethers in bulk [11]. The synthesis of unsymmetrical
⁎ Corresponding author.
E-mail address: rss1805@louisiana.edu (R.S. Srivastava).
https://doi.org/10.1016/j.mcat.2020.110954
Received 18 March 2020; Received in revised form 10 April 2020; Accepted 11 April 2020
2468-8231/©2020ElsevierB.V.Allrightsreserved.

R.R. Singh, et al.
MolecularCatalysis492(2020)110954
and indeed there was an increase in the yield of the products up to 42%
by using MoO2(acac)2 in dichloromethane (DCM) at 30 °C (entry 2). By
increasing temperature up to 60 °C and changing the solvent from DCM
to 1,2 dichloroethane (DCE) we have seen a substantial increase in the
yield of the oxoether products up to 61% with MoO2Cl2 catalyst (entry
3). Entry 4 shows an increase in the yield up to 82% by using
MoO2(acac)2 catalyst and DCE as a solvent at 60 °C. Further, we tested
various molybdenum catalyst such as Mo(CO)6, MoO3 and
(NH4)6Mo7O24.4H2O in entry 5–7 but all in three cases desired oxoether
was obtained in small amounts. Changing solvents such as toluene and
benzene (entry 8 and 9) respectively but the results were not im-
pressive. These solvents failed to show any improvement in reaction
efficiency (Table 1)
Having optimized reaction conditions in hand, we carried out the
substrate scope for the oxoethers moieties. These reactions show broad
substrate scope with a range of alcohols affording desired ethers in all
the cases with good to excellent yield. Results have been presented in
Table 2 showing its scope for symmetrical and non-symmetrical ether
derivatives. We treated 1-phenyl propanol 1b with MoO2(acac)2 the
catalyst in DCE at 60 °C which affords corresponding oxoether 2b in
75% with dr ration of 1:1 (entry 2). Various electron-donating and
withdrawing substitution at the para position of phenyl ethanol was
also investigated under an optimized reaction condition. Desired pro-
ducts 2c–2e in 81–85% with a good dr ratio (entry 3–5) were observed.
Diphenyl carbinol 1f was also a suitable substrate for this catalytic re-
action affording the corresponding oxoether products 2f in 92% yield.
We have also shown the importance of our catalytic system by syn-
thesizing numerous unsymmetrical oxoether products 2g-2j by treating
various aliphatic alcohol such as butanol, hexanol, heptanol and oc-
tanol with 1-phenyl ethanol 1a which afforded the corresponding
product in 89–93% (entry 7–10).
Scheme 1. Comparison between conventional and catalytic method.
ethers directly from two different alcohols is also realized using tran-
sition-metal catalysts [12]. There have been several reports on the
transition metal-catalyzed synthesis of oxoether and thioether (Scheme
2) [7–12], but there is still scope for the development of cheaper and
greener methods for its synthesis.
Herein, we report a highly selective dehydrative formation of
symmetrical and unsymmetrical ethers of two different alcohols which
have been not reported yet. The method also works nicely for the
synthesis of thioether derivatives using the same standard reaction
conditions to afford various substituted thioether derivatives. This
catalytic method can tolerate a wide range of alcohols by generating
water as a sole byproduct under mild conditions by using cheap and
commercially available Mo (VI) catalyst. These reactions proceed via
activation of secondary benzylic alcohols to form symmetrical ethers
and subsequently unsymmetrical ethers formed in the presence of pri-
mary alcohols.
Under a similar reaction condition, we explored the synthesis of
thioethers, and results were pleasing to get desired thioethers 4a in
excellent yield without much loss in the starting materials (Table 3).
Oxo ether 2a was the minor products in this case (< 5%), in the case of
diphenyl disulfide 3a′ a small amount of thiol dimer was detected as the
result of the dimerization of thiols (< 5%). A relatively very small
amount of two byproducts formation indicates the high the efficiency of
this methodology and representing the importance of the catalytic
system.
Results and discussion
During optimization, we treated 1-phenyl ethanol 1a with MoO2Cl2
the catalyst in dichloromethane as a solvent at 30 °C, which afforded
desired oxoether product 2a in 28% yields with two isomeric form dr
the ratio of 1:1, and also a small quantity of styrene 2a′ as a byproduct
(entry 1). The results excited us to explore other Mo catalytic system
The reaction has a broad substrate scope and we have only shown
Scheme 2. Generalization of the metal catalyzed CeO and CeS bond formation.
2

R.R. Singh, et al.
MolecularCatalysis492(2020)110954
Table 1
Optimization of reaction condition.
Entries
Catalyst
Solvent
Yields of 2a (%)b
1c
2c,d
3
MoO2Cl2
DCM
DCM
DCE
28
42
61
82
10
< 5
0
MoO2(acac)2
MoO2Cl2
4
MoO2(acac)2
Mo(CO)6
DCE
5
DCE
6
MoO3
DCE
7
(NH4)6Mo7O24.4H2O
MoO2(acac)2
MoO2(acac)2
DCE
8
Toluene
Benzene
20
29
9
[a] 1a : 0.03 M, [b] yields are reported after isolation from silica coumn, [c] reaction was done at 30 °C, [d] MoO2(acac)2: Bis(acetylacetonato)dioxomo-
lybdenum (VI), DCE : 1,2-dichloroethane.
Table 2
To explore the influence of electronic effects on the dehydration reac-
tion we used various electron-donating and electron-withdrawing sub-
stitution such as p-Me, OMe, Cl and Br at the para position of the phenyl
group in alcohol 1c–1e and 1g delivering the corresponding thioethers
4c–4f in 90–94% yield (entry 3–6). Diphenyl carbinol 1f was also ap-
plicable substrate for this transformation and delivered the corre-
sponding thioether 4g in 95% yield (entry 7).
Substrate scope for the Oxo ether compounds.
We have presented a plausible catalytic cycle for this transformation
(Scheme 3). Both oxoether and thioether product formation is ex-
plained. In the catalytic cycle for the formation of oxoether mo-
lybdenum catalyst coordinates with the alcohol 1 to form the inter-
mediate
A which was simultaneously attacked with the second
molecule of alcohol to afford intermediate B. In this process (A - > B)
there is a cleavage of CeO bond and in situ formation of stable sec-
ondary carbocation takes place. Upon dehydration corresponding ox-
oether products 2 was produced with the liberation of Mo catalyst12h
.
The rationale of thioether formation mechanism for the formation is the
oxidation of alcohol 1 to corresponding ketone [13] C by reducing the
molybdenum and then it was attacked by thiols to give intermediate D
which liberates the water molecule to deliver corresponding thioether
products 4.
Conclusion
[a] 1a : 0.03 M, [b] Yield of the reaction were reported after purification from
silica column, [c] MoO2(acac)2 :Bis(acetylacetonato)dioxomolybdenum (VI),
DCE : 1,2-dichloroethane.
In conclusion, we have developed dehydrative CeO and CeS bond
formation reaction by using cheap and commercially available mo-
lybdenum catalyst delivering oxoethers and thioethers in excellent
yield. The use of cheap catalysts and liberating water as sole byproducts
indicates the foliage and effectiveness of this methodology. Also, this
method highlighted the activation of the hydroxyl functional group of
alcohol selectively affording desired products in high yields. Further
studies were going on in our laboratory for the use of molybdenum
catalyst in various C-heteroatom bond formation reactions.
the variation on the alcohols. Various 1-aryl ethanol 1 and thiophenol
3a was subjected to standard reaction condition delivering the desired
aryl thioethers 4a–4g in excellent yield (entries 1–7). 1-phenyl ethanol
1a and 1-phenyl propanol 1b reacts with thiophenol in the presence of
MoO2(acac)2 afforded desired thioether products 4a and 4b in 89% and
91% yield respectively with a small amount of 2a and 3a′ (entry1−2).
3

R.R. Singh, et al.
MolecularCatalysis492(2020)110954
Table 3
Substrate Scope for the Thioether compounds.
[a] 3a : 0.03 M, [b] Yield of the reaction were reported after purification from silica
column, [c] MoO2(acac)2 :Bis(acetylacetonato)dioxomolybdenum(VI), DCE : 1,2-
dichloroethane.
Scheme 3. Plausible catalytic cycle for the formation of Oxoether and Thioether.
Credit author statement
References
The idea was designed and conceived by principal author Dr.
Radhey S. Srivastava. Alex Whittington an undergraduate student has
done the synthesis of 2 molecule in oxoether and 5 molecules in
thioether substrate scope in the supervision of Dr. Rahul Kumar
Rajmani Singh a post-doctoral research associate. Rest molecules were
synthesized by Dr. Rahul Kumar Rajmani Singh.
[1] (a) S. Mandal, S. Mandal, S.K. Ghosh, P. Sar, A. Ghosh, R. Saha, B. Saha, RSC Adv.
6 (2016) 69605;
(b) M. Pagliaro, R. Ciriminna, H. Kimura, M. Rossi, C.D. Pina, Angew. Chem. Int.
Ed. 46 (2007) 4434;
(c) W.H. Miles, K.B. Connell, J. Chem. Educ. 83 (2006) 285.
[2] A.I. Williamson, Ueber die Theorie Der Aetherbildung, Justus Liebigs Ann. Chem.
77 (1851) 37.
[3] a) A. Suzuki, H.C. Brown, Organic Syntheses Via Boranes 3 Aldrich Chemical
Company, Milwaukee, WI, 2003;
b) X.-Y. Ke, V.W.L. Ng, S.-J. Gao, Y.W. Tong, J.L. Hedrick, Y.-Y. Yang, Biomaterials
35 (2014) 1096.
Declaration of Competing Interest
[4] (a) H. Liu, X. Jiang, Chem. Asian J. 8 (2013) 2546;
(b) Z. Qiao, X. Jiang, Org. Biomol. Chem. 15 (2017) 1942;
(c) G.-P. Lu, C. Cai, Adv. Synth. Catal. 355 (2013) 1271;
(d) E. Calce, M. Leone, F.A. Mercurio, L. Monfregola, S. DeLuca, Org. Lett. 17
(2015) 5646;
Author declare no conflict of interest.
Acknowledgment
(e) J.E. Baer, R.G. Lockwood, J. Am. Chem. Soc. 76 (1954) 1162;
(f) O. Kundrat, V. Eigner, H. Dvorakova, P. Lhotak, Org. Lett. 13 (2011) 4032;
(g) S. Murru, B.K. Patel, J. LeBras, J. Muzart, J. Org. Chem. 74 (2009) 2217;
(h) Y. Yang, Z. Ye, X. Zhang, Y. Zhou, X. Ma, H. Cao, H. Li, L. Yu, Q. Xu, Org.
The authors are grateful to the University of Louisiana at Lafayette
for financial support of this work.
4

R.R. Singh, et al.
MolecularCatalysis492(2020)110954
Biomol. Chem. 15 (2017) 9638.
(b) N. Sakai, T. Moriya, T. Konakahara, J. Org. Chem. 72 (2007) 5920;
[5] S.-S. Meng, Q. Wang, G.-B. Huang, L.-R. Lin, J.-L. Zhao, A.S.C. Chan, RSC Adv. 8
(2018) 30946.
(c) M.B. Sassaman, K.D. Kotian, G.K.S. Prakash, G.A. Olah, J. Org. Chem. 52 (1987)
4314.
[6] (a) S. Podder, J. Choudhury, S. Roy, J. Org. Chem. 72 (2007) 3129;
(b) L. Zhang, A. Gonzalez-de-Castro, C. Chen, F. Li, S. Xi, L. Xu, J. Xiao, Mol. Catal.
433 (2017) 62;
[10] (a) J. Roane, O. Daugulis, Org. Lett. 15 (2013) 5842;
(b) F.-J. Chen, S. Zhao, F. Hu, K. Chen, Q. Zhang, S.-Q. Zhang, B.-F. Shi, Chem. Sci.
4 (2013) 4187; (2012) 7313;
(c) S. Shirakawa, S. Kobayashi, Org. Lett. 9 (2007) 311;
(d) Y.-L. Liu, L. Liu, Y.-L. Wang, Y.-C. Han, D. Wang, Y.-J. Chen, Green Chem. 10
(2008) 635;
(c) S.-Y. Zhang, G. He, Y. Zhao, K. Wright, W.A. Nack, G. Chen, J. Am. Chem. Soc.
134 (2012) 7313;
(d) W. Li, P. Sun, J. Org. Chem. 77 (2012) 8362.
(e) A. Zhu, L. Li, J. Wang, K. Zhuo, Green Chem. 13 (2011) 1244;
(f) K. Motokura, N. Fujita, K. Mori, T. Mizugaki, K. Ebitani, K. Kaneda, Angew.
Chem. Int. Ed. 45 (2006) 2605;
[11] (a) K. Manabe, S. limura, X.-M. Sun, S. Kobayashi, J. Am. Chem. Soc. 124 (2002)
11971;
(b) K. Tanabe, W.F. Hölderich, Appl. Catal. A Gen. 181 (1999) 399;
(c) I. Nowak, M. Ziolek, Chem. Rev. 99 (1999) 3603;
(d) K. Klier, A. Beretta, Q. Sun, O.C. Feeley, R.G. Herman, Catal. Today 36
(1997) 3.
(g) J. Li, X. Zhang, H. Shen, Q. Liu, J. Pan, W. Hu, Y. Xiong, C. Chen, Adv. Synth.
Catal. 357 (2015) 3115;
(h) Q. Xu, H. Xie, P. Chen, L. Yu, J. Chen, X. Hu, Green Chem. 17 (2015) 2774.
[7] (a) P.E. Maligres, J. Li, S.W. Krska, J.D. Schreier, I.T. Raheem, Angew. Chem. Int.
Ed. 51 (2012) 9071;
[12] (a) R.M.P. Veenboer, S.P. Nolan, Green Chem. 17 (2015) 3819;
(b) A.B. Cuenca, G. Mancha, G. Asensio, M. Medio-Simón, Chem. Eur. J. 14 (2008)
1518;
(b) S.V. Ley, A.W. Thomas, Angew. Chem. Int. Ed. 42 (2003) 5400;
(c) J.F. Hartwig, Angew. Chem. Int. Ed. 37 (1998) 2046.
[8] (a) K.C.K. Swamy, N.N.B. Kumar, E. Balaraman, K.V.P.P. Kumar, Chem. Rev. 109
(2009) 2551;
(c) J. Kim, D.-H. Lee, N. aluntharage, C.S. Yi, ACS Catal. 4 (2014) 3881;
(d) K.J. Miller, M.M. Abu-Omar, Eur. J. Org. Chem. (2003) 1294;
(e) G.V.M. Sharma, A.K. Mahalingam, J. Org. Chem. 64 (1999) 8943;
(f) Z. Zhu, J.H. Espenson, J. Org. Chem. 61 (1996) 324;
(g) K. Kucinski, G. Hreczycho, Eur. J. Org. Chem. (2017) 5572;
(h) P.K. Sahoo, S.S. Gawali, C. Gunanathan, ACS Omega 3 (2018) 124.
[13] I. Sorribes, A. Corma, Chem. Sci. 10 (2019) 3130.
(b) D. Ma, Q. Cai, Acc. Chem. Res. 41 (2008) 1450;
(c) T.Y.S. But, P.H. Toy, Chem. Asian J. 2 (2007) 1340;
(d) K. Kunz, U. Scholz, D. Ganzer, Synlett (2003) 2428.
[9] (a) M.C. Haibach, C. Guan, D.Y. Wang, B. Li, N. Lease, A.M. Steffens, K. Krogh-
Jespersen, A.S. Goldman, J. Am. Chem. Soc. 135 (2013) 15062;
5