Selenium-Catalyzed Carbonylative Synthesis of 2-Benzimidazolones from 2-Nitroanilines with TFBen as the CO Source

Article abstract of DOI:10.1002/ejoc.201801739

A selenium-catalyzed carbonylative reaction for the synthesis of 2-benzimidazolones from 2-nitroanilines has been developed. In this strategy, to avoid the usage of toxic CO gas, TFBen (benzene-1,3,5-triyl triformate) was used as a solid and stable CO precursor, and a variety of desired 2-benzimidazolones were produced in moderate to excellent yields.

Full text of DOI:10.1002/ejoc.201801739

A Journal of
Accepted Article
Title: Selenium-Catalyzed Carbonylative Synthesis of 2-
Benzimidazolones from 2-Nitroanilines with TFBen as the CO
Source
Authors: xinxin qi, rong zhou, jin-bao peng, jun ying, and Xiao-Feng
Wu
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201801739
Link to VoR: http://dx.doi.org/10.1002/ejoc.201801739
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10.1002/ejoc.201801739
European Journal of Organic Chemistry
COMMUNICATION
Selenium-Catalyzed Carbonylative Synthesis of 2-
Benzimidazolones from 2-Nitroanilines with TFBen as the CO Source
Xinxin Qi,[a] Rong Zhou,[a] Jin-Bao Peng,[a] Jun Ying,[a] Xiao-Feng Wu*[a,b]
Abstract:
A selenium-catalyzed carbonylative reaction for the
Results and Discussion
synthesis of 2-benzimidazolones from 2-nitroanilines has been
developed. In this strategy, to avoid of the usage of toxic CO gas,
TFBen (benzene-1,3,5-triyl triformate) was used as a solid and
stable CO precursor, and a variety of desired 2-benzimidazolones
were produced in moderate to excellent yields.
Initially, with 2-nitroaniline as the model substrate,
selenium as the catalyst and DBU as the base in DMF at 120 °C
for 16 h, the desired product was obtained in 5% yield (Table 1,
entry 1). The yield of the product were increased as the reaction
time prolonged to 24 h, and has no further improvement with
longer reaction time (Table 1, entries 2-4). The catalyst loading
was then tested, resulting better yields with lower amounts of
catalyst (Table 1, entries 5-6). It was noteworthy that organic
bases have dramatically effects on the reaction results (Table 1,
entries 7-12). In addition to DBU, Et3N, DABCO, TMEDA, DiPEA,
DMAP and DMEDA were also investigated, to our delight, 71%
yield was observed by using Et3N as the base (Table 1, entry 7).
Furthermore, when the amount of Et3N varied to 1 mmol and 3
mmol, the yield of the product decreased (Table 1, entries 13-
14).
Introduction
2-Benzimidazolones and their derivatives represent an important
class of heterocyclic compounds that frequently appeared in
natural products, pharmaceuticals, and bioactive compounds.[1]
Their diverse biological activities attracted much attentions and
several synthetic methods have been reported. The
conventional synthetic approaches for 2-benzimidazolones
mainly rely on the reaction of phosgene with o-
phenylenediamines. However, this strategy has several
drawbacks including the use of high toxic and corrosive
phosgene and subsequently the generation of hydrogen chloride
side product. Although alternative synthetic procedures have
been explored as well, the requirement of specific substrates or
high pressure of carbon monoxide gas remains challenge.[2]
Thus, to develop methodology under mild reaction conditions
are highly in demand.
Table 1. Screening of reaction conditions.[a]
Entry
1
Se (mmol)
0.5
Base
DBU
Time (h)
16
Yield (%)[b]
5
In recent years, carbonylation reaction has drawn a lot
interest for their widely application in both academic and
industrial fields.[3] In most cases, noble transition-metal catalyst
such as palladium, ruthenium and rhodium are needed. In
addition, CO gas is utilized as the carbonyl source in most of the
carbonylative transformations. However, the high toxic, odorless,
and flammable nature of gaseous CO limited their usage in
laboratory scales. Hence, much efforts have been put in the
development of CO gas-free procedures, and a variety of CO
surrogates have been developed during the last few years, such
as metal carbonyl complexes,[4] paraformaldehyde,[5] formates,[6]
2
3
4
5
6
7
8
9
10
11
12
13[c]
14[d]
0.5
0.5
0.5
0.2
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
DBU
DBU
DBU
DBU
DBU
Et3N
DABCO
TMEDA
DiPEA
DMAP
DMEDA
Et3N
20
24
28
24
24
24
24
24
24
24
24
24
16
20
20
27
28
71
30
32
<5
<5
<5
43
37
0.1
Et3N
24
[9]
formamides,[7] alcohol,[8] CO2 and others[10] were reported.
[a] Reaction condition: 2-nitroaniline (1 mmol), Se (0.1-0.5
mmol), base (2 mmol), DMF (2 mL), TFBen (1 mmol),
120 °C, 16-28 h. [b] Isolated yields. [c] Et3N (1 mmol). [d]
Et3N (3 mmol). DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene.
DABCO:
tetramethylethylenediamine.
More recently, our group explored a variety of carbonylation
reactions with formic acid as the CO source,[11] and in our
continuous work on CO precursor study, TFBen (benzene-1,3,5-
triyl triformate) was developed as a solid, stable, and convenient
CO source.[12] Herein, we wish to disclose a selenium-catalyzed
carbonylation reaction for the synthesis of 2-benzimidazolones
from 2-nitroanilines with TFBen as the CO source.
1,4-diazabicyclo[2.2.2]octane.
DiPEA:
TMEDA:
N,
N-
diisopropylethylamine. DMAP: 4-dimethylaminopyridine.
DMEDA: 1,2-dimethylethylenediamine.
With the optimal reaction conditions in hand, we next
investigated the substrates scope, and the results were
summarized in Table 2. Aryl substrates with electron-donating
groups including methyl, tert-butyl, and methoxy groups gave
the corresponding products in moderate to good yields (2ab-2af).
It was noteworthy that those substrates with methyl group
substituted at ortho- and para-position to nitro group resulted in
higher yield than meta-substitution (2ab, 2ac vs. 2ad). Halides
[a]
Dr. X. Qi, R. Zhou, Dr. J.-B. Peng, Dr. J. Ying, Prof. Dr. X.-F. Wu
Department of Chemistry, Zhejiang Sci-Tech University
Xiasha Campous, Hangzhou 310018, People’s Republic of China
E-mail: xiao-feng.wu@catalysis.de
https://www.catalysis.de/mitarbeiter/wu-xiao-feng/
[b]
Leibniz-Institut für Katalyse e.V. an der Universität Rostock
Albert-Einstein-Strasse 29a, 18059 Rostock (Germany)
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201801739
European Journal of Organic Chemistry
COMMUNICATION
groups including chloro, bromo and iodo groups worked well to
give the corresponding products in moderate yields (2ag-2aj).
Table 2. Reaction scope on 2-nitroanilines.[a]
[a] Reaction condition: 2-nitroanilines/2-nitrophenols (1 mmol),
Se (0.1 mmol), base (2 mmol, Et3N for 2-nitroanilines, DMAP for
2-nitrophenols), DMF (2 mL), TFBen (1 mmol), 120 °C, 24 h.
isolated yield.
Electron-withdrawing group such as trifluoromethyl, and
ester groups provided the desired products in excellent yields
(2ak, 2am), however, cyano group resulted the final product in
very low yield (2al). Moreover, a series of substitutions on amine
group have been studied as well. Alkyl groups involving methyl,
butyl, and allyl groups furnished the target products in moderate
to good yields (2ba-2bc). However, compare to alkyl groups, 30%
yield was obtained with ketone group (2bd). Further
investigation showed that aryl groups with electron-donating,
electron-withdrawing and halides groups were all well tolerated
to produce the corresponding products in good to excellent
yields (2be-2bq). Furthermore, 2-nitrophenols were also
examined, result the target products in moderate yields (2ca-
2cc).
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10.1002/ejoc.201801739
European Journal of Organic Chemistry
COMMUNICATION
Based on the above results and literatures,2,13 a plausible
reaction mechanism was proposed in scheme 1. Carbonyl
selenide (SeCO) is initially formed from the reaction of selenium
and CO, which is generated from TFBen in the presence of base
or heating. At the same time, deoxygenation of nitroanilines 1
with SeCO, results in the nitrene intermediates I, followed by the
reaction with CO/Se to provide isocyanate II. And then an amine
or hydroxyl group will react with the in-suit formed isocyanate
group to afford the target product 2.
The authors thank the financial supports from NSFC
(21602201, 21772177, 21472174) and Zhejiang Natural
Science Fund for Distinguished Young Scholars
(LR16B020002). X.-F. Wu appreciates the general support
from Professors Armin Börner and Matthias Beller in LIKAT.
Keywords: 2-benzimidazolones • selenium • carbonylation •
TFBen • cascade reaction
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In conclusion, a convenient and efficient carbonylative
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benzimidazolones. With elemental selenium as the catalyst,
TFBen as the CO source, a wide range of 2-nitroanilines were
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European Journal of Organic Chemistry
COMMUNICATION
COMMUNICATION
Carbonylative synthesis of heterocycles
Xinxin Qi, Rong Zhou, Jin-Bao Peng, Jun
Ying, Xiao-Feng Wu*
Page No. – Page No.
A convenient and efficient carbonylative procedure has been established for the
synthesis of 2-benzimidazolones. With elemental selenium as the catalyst, TFBen
as the CO source, a wide range of 2-nitroanilines were transformed into the final
products in moderate to high yields.
Selenium-Catalyzed Carbonylative
Synthesis of 2-Benzimidazolones
from 2-Nitroanilines with TFBen as the
CO Source
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