Dehydration of Aldoximes Using PhSe(O)OH as the Pre-Catalyst in Air

Article abstract of DOI:10.1021/acs.orglett.5b03011

PhSe(O)OH was found to be a good pre-catalyst for aldoxime dehydrations in open air. Compared with the previously reported (PhSe)₂-H₂O₂ system, it is more stable and milder, affording broader application scopes due to a higher functional group tolerance. The control experiments for mechanism study disclosed that air was the key factor for the reaction to maintain enough concentration of PhSeOH, which should be the real catalytic species.

Full text of DOI:10.1021/acs.orglett.5b03011

Letter
pubs.acs.org/OrgLett
Dehydration of Aldoximes Using PhSe(O)OH as the Pre-Catalyst in Air
Xu Zhang, Jingjing Sun, Yuanhua Ding, and Lei Yu*
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Jiangsu Key
Laboratory of Zoonosis, School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu 225002, China
*
S Supporting Information
ABSTRACT: PhSe(O)OH was found to be a good pre-catalyst for aldoxime dehydrations
in open air. Compared with the previously reported (PhSe) -H O system, it is more stable
2
2
2
and milder, affording broader application scopes due to a higher functional group tolerance.
The control experiments for mechanism study disclosed that air was the key factor for the
reaction to maintain enough concentration of PhSeOH, which should be the real catalytic species.
elenium is an important and necessary trace element for
human beings and has very wide applications in
the stable and accessible PhSe(O)OH as a pre-catalyst in
S
aldoxime dehydration. Herein, we wish to report our findings.
The dehydration of benzaldoxime 1a was chosen as the model
reaction for conditional optimizations. Based on our previous
reports, 1 mmol of 1a and 0.05 mmol of PhSe(O)OH were
initially heated in 2 mL of MeCN at 65 °C for 24 h. The GC
analysis indicated that the desired product 2a was generated in
more than 99% yield (Table 1, entry 1). Using DMSO as the
solvent, the dehydration of 1a also led to 2a in excellent yield
biochemistry, medicinal chemistry, organic synthesis, and
1
,2
3
material science. Despite its toxicity, the green side of this
4
element began to draw attention in recent years. Among
reported works, organoselenium catalysis is an important and
unique subject that presents additional opportunities to develop5
novel green synthetic methods with industrial potential.
Compared with transition metals, selenium can be metabolized
in organisms and thus does not accumulate in the body and is safe
(
(
Table 1, entry 2), but in DMF, the product yield decreased
Table 1, entry 3). The reaction in the nontoxic solvent EtOH
3
for the environment. Selenium is much less expensive than
6
noble metals, and the organoselenium catalysts are sufficiently
gave 2a in very poor yield (Table 1, entry 4), but interestingly, it
7
robust to be recycled and reused with little deactivation. The
organoselenium-catalyzed reactions are performed under mild
a
Table 1. Condition Optimizations
7
,8
conditions, free of ligands or additives with green procedures.
Recently, organoselenium catalysts have been successfully
7
−9
employed in a series of useful transformations.
During our ongoing investigations of green synthetic method-
ologies, we also paid attention to organoselenium cataly-
b
c
entry
solvent
MeCN
cat. loading (mol %)
2a (%)
7
b−e,8a,b
sis.
In 2014, we reported the dehydration of aldoximes
1
5
>99
97
76
27
76
77
72
73
74
95
92
91
88
76
to produce nitriles. The reaction was catalyzed by 3-
2
DMSO
DMF
5
FC H SeOH, which was generated in situ from (3-FC H Se)
6
4
6
4
2
3
5
7d
with equal molar ratio of H O . The method is clean because of
2
2
4
EtOH
5
the recyclable catalyst that generates no waste and the avoidance
of chemical dehydrant and transition metal catalyst. However,
d
5
EtOH/H O (1:1)
5
2
6
H O
2
5
since H O is a strong and somewhat unstable oxidant, it is not
2
2
7
cyclohexane
toluene
5
convenient to be accurately weighted in a catalytic amount,
especially for such small-scaled reactions. In addition, H O may
8
5
2
2
9
5
also react with the sensitive functional groups in substrates, thus
leading to the limited application scopes of the reaction.
Therefore, developing a more stable catalyst-system will
obviously improve the practicability of the methodology. In
our investigations on organoselenium-catalyzed reactions, we
10
11
12
13
14
MeCN
MeCN
MeCN
MeCN
MeCN
4
3
2
1
0.5
a
observed (PhSe) in GC or TLC analysis, even when the reaction
1 mmol of 1a and 2 mL of solvent were employed; Unless given
special instructions, the reaction scales in this article were 1 mmol.
Catalyst loadings based on 1a. GC yields based on 1a with biphenyl
2
8b
was performed with excess H O . It was suggested that the high
2
2
b
c
valence organoselenium species might be unstable and could be
d
used as the internal standard. Volume ratio inside the parentheses.
reduced by substrates or solvents to the low valence (PhSe) and
2
the transformations possibly happened via the intermediate
PhSeOH, the catalytic species for aldoxime dehydration. Inspired
by the above phenomena and speculations, we tried to employ
Received: October 18, 2015
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b03011
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
proceeded smoothly in aqueous conditions (Table 1, entries 5−
those with (3-FC H Se) /H O . It was clear that the reactions
6
4
2
2
2
6), possible because of the fact that ethanol over reduced the
catalyzed by PhSe(O)OH afforded the nitriles 2 in higher yields
than those by (3-FC Se) /H , as previously reported
(Table 2, entries 1−20), especially for the dehydrations of 1f,
j, 1k, 1n, 1p, 1q, and 1r, which might be sensitive to H O and
catalyst to the inactive (PhSe) , as acetaldehyde was detected by
6
H
7d
4
2
O
2 2
2
1
0
GC−MS. The nonpolar solvents such as cyclohexane and
toluene were also tested, giving 2a in moderate yields (Table 1,
entries 7−8). It should be noted that the reaction could also
occur without solvent, indicating the great potential of this
methodology in industry production (Table 1, entry 9). We also
tried to perform the reaction with less catalyst, but the product
yields decreased gradually with the reduction in the catalyst
loadings (Table 1, entries 10−14). Thus, using 5 mol % of
PhSe(O)OH and with MeCN as the solvent should be the
optimized conditions. There is no need to further screen the
1
2
2
7
d
thus resulted in very poor product yields previously. It was
noticed that the dehydration of thiophene-2-carbaldehydoxime
1
q afforded thiophene-2-carbonitrile 2q in very low yield, while
thiophene-2-carbaldehyde 3q, the byproduct, was generated
Table 1, entry 18). A series of organoselenium catalysts were
then tested to improve the reaction, and 3-FC H Se(O)OH was
(
6
4
screened out to be the better one, giving 2q in the acceptable 52%
10
yield (Table 1, entries 19 vs 18). The example indicated that
the methodology could be further improved by screenings of the
catalysts for certain unfavorable substrates.
7b−e
organoselenium catalysts as in the previous works
because
PhSe(O)OH is one of the most accessible organoselenium
compounds, and it afforded almost quantitative product yield.
The application scopes of this methodology were also
examined. In order to facilitate the readers to understand the
advantages of the reactions using PhSe(O)OH as pre-catalyst
The reaction mechanisms were our next concern. In order to
gain enough hints for study, a series of control experiments were
taken. For its excellent performances (Table 2, entry 16),
aldoxime 1o was chosen as the model substrate and its
dehydrations were performed using various catalysts under
different conditions. The role of air in the reaction was
investigated. As shown in Table 3, the dehydration of 1o under
over those with (PhSe) /H O in product yields, the results were
2
2
2
listed in parallel (Table 2). The Y1 indicate the product yields of
the reactions using PhSe(O)OH as pre-catalyst, while Y2 was
Table 3. Control Experiments
Table 2. Application Scope Examinations
a
entry
Se cat. (loading/mol %)
conditions
air
2o (%)
1
2
3
4
5
PhSe(O)OH (5)
PhSe(O)OH (5)
PhSe(O)OH (5)
>99
b
c
N2
<5
d
c
O2
87
c
(PhSe) (2.5)
air
12
2
d
c
(PhSe) (2.5)
O2
67
2
a
b
Isolated yields based on 1o. (PhSe) was recovered in >99% yield
2
c
based on the precatalyst PhSe(O)OH. Reactions not completed.
d
3
Introduced by a tiny glass tunnel (1 atm; flow rate, 0.88 cm /s).
air afforded the nitrile 2o in nearly quantitative yield, but when it
was taken in N , almost no reaction happened (Table 3, entries 1
2
vs 2). Considering the fact that (PhSe) was recycled in >99%
2
yield after the reaction in N (Table 3, entry 2), it was suggested
2
that PhSe(O)OH was reducible in the reaction and air was the
key to reoxidize it into the active catalytic species. The reaction
with pure O also resulted in the incomplete reaction and the
2
reduced product yield (Table 3, entries 3 vs 1) because PhSeOH,
the medium valent selenium intermediate as we previously
7d
reported, should be the real catalytic species in the reaction.
The reactions using (PhSe) as pre-catalyst were examined. In air,
2
it gave 2o in very low yield, but with the assistance of strong
oxidant O , 2o was obtained in moderate yield (Table 3 entries 4
2
vs 5). The phenomena further supported the above hypothesis
on mechanism. Further GC−MS analysis showed that the
starting material aldoxime reduced the PhSe(O)OH, while the
10
solvent MeCN and product nitrile were stable.
a
Based on the above experimental results as well as refs 7 and 8,
a plausible mechanism is given below (Scheme 1). As found in
our previous work and proved by GC−MS analysis, the
Isolated yields of 2 for reactions performed under the optimized
b
conditions of Table 1, entry 1. The reactions were monitored by
TLC. Isolated yields of 2 for reactions performed using (3-
FC H Se) /H O as in ref 7d. Reactions performed in 5 mmol
scale. Reaction performed at 100 °C in a sealed tube. 3-
c
d
PhSe(O)OH was reducible by the starting material aldoxime
6
4
2
2
2
e
f
8b,10
to give the (PhSe)2.
The transformation proceeded through
FC H Se(O)OH was employed as catalyst.
PhSeOH 4, the active catalytic species for aldoxime dehydra-
6
4
B
DOI: 10.1021/acs.orglett.5b03011
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 1. Possible Mechanisms
REFERENCES
■
(
1) Selected reviews ormonographs, see: (a) Wirth, T., Ed.
Organoselenium Chemistry; Topics in Current Chemistry; Springer: Berlin,
Germany, 2000; Vol. 208. (b) Ogawa, A. In Main Group Metals in
Organic Synthesis; Yamamoto, H.; Oshima, K., Eds.; Wiley-VCH:
Weinheim, Germany, 2004; Vol. 2, p 813. (c) Wirth, T.,
Ed.Organoselenium Chemistry: Synthesis and Reactions; Wiley-VCH:
Weinheim, Germany, 2011. (d) Godoi, B.; Schumacher, R. F.; Zeni, G.
Chem. Rev. 2011, 111, 2937. (e) Nomoto, A.; Higuchi, Y.; Kobiki, Y.;
Ogawa, A. Mini-Rev. Med. Chem. 2013, 13, 814. (f) Weekley, C. M.;
Harris, H. H. Chem. Soc. Rev. 2013, 42, 8870.
(2) For selected articles, see: (a) Casola, K. K.; Back, D. F.; Zeni, G. J.
Org. Chem. 2015, 80, 7702. (b) Maity, P.; Kundu, D.; Roy, R.; Ranu, B.
C. Org. Lett. 2014, 16, 4122. (c) Yu, L.; Wu, Y.-L.; Chen, T.; Pan, Y.; Xu,
Q. Org. Lett. 2013, 15, 144 and references therein..
(3) The organoselenium compounds are obviously less toxic than
inorganic selenium compounds such as SeO , H SeO , etc. Moreover,
2
2
3
compared with transitional metals, selenium could be metabolized by
creatures and is thus much safer to environment. An adequate
englobement of selenium is even good for health. For details, see:
Rayman, M. P. Lancet 2012, 379, 1256.
7
d
tion. Air should be the key factor to maintain enough PhSeOH
concentration for the dehydration (Table 3, entries 1 vs 2), but
(4) (a) Santoro, S.; Azeredo, J. B.; Nascimento, V.; Sancineto, L.;
stronger oxidant such as O might oxidize 4 to PhSe(O)OH and
thus restrained the reaction (Table 3, entries 3 vs 1). The
dehydration of 4 led to the highly active species 5,
reacted with the aldoximes 1 to produce the intermediates 6. The
rearrangement of 6 led to the intramolecular hydrogen bond-
stabilized intermediate 7, which decomposed to nitriles 2 and
regenerated the catalytic species 4 through a well-known
selenoxide syn-elimination.
In conclusion, we developed a more practical methodology for
the dehydration of aldoxime to produce nitriles using PhSe(O)-
OH as the pre-catalyst. The methodology has more compre-
hensive application scopes and produces nitriles in higher yields
than in previous work. Air was found to be the key factor for the
reaction and its role has been well investigated through control
experiments. The continuous systematic studies on organo-
selenium catalysis are ongoing in our laboratory.
2
Braga, A. L.; Santi, C. RSC Adv. 2014, 4, 31521. (b) Santi, C.; Tidei, C.
Electrophilic Selenium/Tellurium Reagents: Reactivity and Their
Contribution to Green Chemistry. In The Chemistry of Organic Selenium
and Tellurium Compounds; Rappoport, Z., Ed.; John Wiley & Sons:
Chichester, U.K., 2013; Vol. 4, pp 569−655.
(5) For reviews, see: (a) Freudendahl, D. M.; Santoro, S.; Shahzad, S.
A.; Santi, C.; Wirth, T. Angew. Chem., Int. Ed. 2009, 48, 8409. (b) Santi,
C.; Santoro, S.; Battistelli, B. Curr. Org. Chem. 2010, 14, 2442.
7d,11
which
7d
12
(
(
1
c) Breder, A.; Ortgies, S. Tetrahedron Lett. 2015, 56, 2843.
d) Młochowski, J.; Wojtowicz-Młochowska, H. Molecules 2015, 20,
0205.
6) The price of 99.9% selenium powder was ca. $54/kg in China in
September, 2015.
7) (a) Sancineto, L.; Tidei, C.; Bagnoli, L.; Marini, F.; Lenardao, E. J.;
́
(
(
Santi, C. Molecules 2015, 20, 10496. (b) Yu, L.; Ye, J.-Q.; Zhang, X.;
Ding, Y.-H.; Xu, Q. Catal. Sci. Technol. 2015, 5, 4830. (c) Zhang, X.; Ye,
J.-Q.; Yu, L.; Shi, X.-K.; Zhang, M.; Xu, Q.; Lautens, M. Adv. Synth. Catal.
2
015, 357, 955. (d) Yu, L.; Li, H.-Y.; Zhang, X.; Ye, J.-Q.; Liu, J.-P.; Xu,
ASSOCIATED CONTENT
Supporting Information
Q.; Lautens, M. Org. Lett. 2014, 16, 1346. (e) Yu, L.; Wang, J.; Chen, T.;
Wang, Y.-G.; Xu, Q. Appl. Organomet. Chem. 2014, 28, 652.
■
*
S
(8) (a) Yu, L.; Wu, Y.-L.; Cao, H.-E.; Zhang, X.; Shi, X.-K.; Luan, J.;
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.5b03011.
Chen, T.; Pan, Y.; Xu, Q. Green Chem. 2014, 16, 287. (b) Yu, L.; Wang,
J.; Chen, T.; Ding, K.-H.; Pan, Y. Youji Huaxue 2013, 33, 1096. (c) Santi,
C.; Di Lorenzo, R.; Tidei, C.; Bagnoli, L.; Wirth, T. Tetrahedron 2012,
Experimental details, mechanism study by GC−MS,
6
8, 10530. (d) Santoro, S.; Santi, C.; Sabatini, M.; Testaferri, L.; Tiecco,
1
13
product characterizations, and H and C NMR spectra
M. Adv. Synth. Catal. 2008, 350, 2881. (e) ten Brink, G.-J.; Fernandes, B.
C. M.; van Vliet, M. C. A.; Arends, I. W. C. E.; Sheldon, R. A. J. Chem. Soc.
Perkin Trans. 1 2001, 224.
(
PDF)
(
9) (a) Cresswell, A. J.; Eey, S. T.-C.; Denmark, S. E. Nat. Chem. 2015,
AUTHOR INFORMATION
Corresponding Author
E-mail: yulei@yzu.edu.cn.
■
*
7
2
, 146. (b) Zhang, X.-L.; Guo, R.-Z.; Zhao, X.-D. Org. Chem. Front. 2015,
, 1334. (c) Deng, Z.-M.; Wei, J.-L.; Liao, L.-H.; Huang, H.-Y.; Zhao, X.-
D. Org. Lett. 2015, 17, 1834. (d) Ortgies, S.; Breder, A. Org. Lett. 2015,
1
1
7, 2748. (e) Chen, F.; Tan, C. K.; Yeung, Y.-Y. J. Am. Chem. Soc. 2013,
35, 1232. (f) Trenner, J.; Depken, C.; Weber, T.; Breder, A. Angew.
Notes
The authors declare no competing financial interest.
Chem., Int. Ed. 2013, 52, 8952.
10) For details, please see Supporting Information.
(
ACKNOWLEDGMENTS
(11) (a) Kang, S.-I.; Kice, J. L. J. Org. Chem. 1985, 50, 2968. (b) Kice, J.
L.; McAfee, F.; Slebocka-Tilk, H. J. Org. Chem. 1984, 49, 3100. (c) Kice,
J. L.; McAfee, F.; Slebocka-Tdk, H. Tetrahedron Lett. 1982, 23, 3323.
■
This work was supported by NNSFC (21202141, 21173182),
Priority Academic Program Development (PAPD) of Jiangsu
Higher Education Institutions, Yangzhou Nature Science
Foundation (YZ2014040), the Opening Foundation of the
Key Laboratory of Environmental Materials and Engineering of
Jiangsu Province (K14010) and the Open Project Program of
Jiangsu Key Laboratory of Zoonosis (R1509). We thank Prof.
Shouyun Yu (Nanjing University) for kind suggestions. We
thank the analysis centre of Yangzhou University for assistances.
(
d) Reich, H. J.; Willis, W. W., Jr.; Wollowitz, S. Tetrahedron Lett. 1982,
3, 3319.
12) (a) Reich, H. J. Acc. Chem. Res. 1979, 12, 22. (b) Liotta, D. Acc.
Chem. Res. 1984, 17, 28.
2
(
C
DOI: 10.1021/acs.orglett.5b03011
Org. Lett. XXXX, XXX, XXX−XXX