Recycling of carbon and silicon wastes: Room temperature formylation of N-H bonds using carbon dioxide and polymethylhydrosiloxane

Article abstract of DOI:10.1021/ja211527q

A highly active organocatalytic system based on N-heterocyclic carbenes has been designed for the formylation of N-H bonds in a large variety of nitrogen molecules and heterocycles, using two chemical wastes: CO₂ and polymethylhydrosiloxane (PMHS).

Full text of DOI:10.1021/ja211527q

Communication
pubs.acs.org/JACS
Recycling of Carbon and Silicon Wastes: Room Temperature
Formylation of N−H Bonds Using Carbon Dioxide and
Polymethylhydrosiloxane
Olivier Jacquet, Christophe Das Neves Gomes, Michel Ephritikhine, and Thibault Cantat*
CEA, IRAMIS, SIS2M, CNRS UMR 3299, CEA/Saclay, 91191 Gif-sur-Yvette, France
S
* Supporting Information
Using CO2, a carbon waste, for the formylation of N−H
ABSTRACT: A highly active organocatalytic system
based on N-heterocyclic carbenes has been designed for
the formylation of N−H bonds in a large variety of
nitrogen molecules and heterocycles, using two chemical
wastes: CO2 and polymethylhydrosiloxane (PMHS).
bonds is attractive yet challenging because of the thermody-
namic stability of CO2. Conversion of Me2NH, Et2NH, and
PhNH2 to their formamides using CO2 and H2, as an energy
source, is a well-known process.5 Nevertheless, hydrogenation
of CO2 in the presence of an amine requires metal catalysts
working at high temperature and pressure. Using silanes as
reductants, we recently developed an organocatalytic version of
this reaction, with nitrogen bases (TBD) as catalysts (eq 1).6
However, this so-called diagonal reaction is limited to basic
amines and only proceeds at 100 °C with phenylsilane, whereas
low working temperatures, renewable or disposable energy
inputs, and large application spectra are required to develop
efficient and meaningful methods for CO2 recycling. To
circumvent these limitations, it is critical to design highly
active catalysts, and herein, we report that N-heterocyclic
carbenes (NHCs) are excellent catalysts able to promote the
formylation of a large variety of N−H bonds in amines, imines,
hydrazines, and N-heterocycles using two wastes: CO2 and
polymethylhydrosiloxane (PMHS), an abundant and nontoxic
byproduct of the silicone industry (Scheme 1).
hile greenhouse gases emissions are reaching alarming
Wlevels, fossil fuels still represent 80% of the world energy
portfolio and 95% of our organic chemical commodities rely on
nonrenewable resources, mostly hydrocarbons.1 As CO2 is the
ultimate waste of this intensive utilization of carbon resources,
its recycling urges the necessity to build a balanced carbon
cycle.2 In this context, utilizing CO2 as a C1 building block to
produce platform chemicals as an alternative to petrochemistry
has a double advantage of reusing CO2 while sparing fossil
resources and avoiding CO2 emissions from their use.
Formamide derivatives, such as N-methylformamide or N,N-
dimethylformamide (DMF), are important solvents and key
intermediates in the synthesis of adhesives, pesticides, and
drugs and formulation of polymers.3 In the industry,
formamides are typical petrochemicals and are synthesized via
a multistep process, by formylation of amines with CO or
aminolysis of formic acid and methylformate, using carbon
monoxide as a C1-carbon source (Scheme 1).3,4
Scheme 1
Whereas preliminary theoretical calculations have shown that
TBD is not nucleophilic enough to activate organosilanes,6
NHCs are proven catalysts for transformations requiring
activation of Si−H, Si−O, and Si−CN bonds.7 The reductive
functionalization of CO2, using PhSiH3 and morpholine, was
therefore attempted using IMes as a catalyst. To our delight,
formation of N-formylmorpholine (2a) was complete after only
2 h at room temperature (RT) and under 1 bar of CO2, while
TBD shows no activity under these conditions. A limited
screening of NHCs was therefore explored to map the steric
and electronic properties influencing the catalytic activity of the
carbene (Table 1). The six NHCs tested in the formylation of
morpholine proved to be active at RT. However, unsaturated
carbenes, such as IMes and IPr, perform significantly better
than their saturated analogues, s-IMes and s-IPr, and the
Received: December 9, 2011
Published: January 31, 2012
© 2012 American Chemical Society
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Table 1. Organocatalytic Formylation of Morpholine Using
CO2, PhSiH3, and NHCs
Scheme 2. Scope of the Organocatalytic Formylation of
N−H Bonds Using CO2 and PhSiH3
a
a
entry
catalyst
yield [%]
1
2
3
4
5
6
IPr
99
69
24
25
35
30
IMes
s-IPr
s-IMes
Cl2-IPr
ItBu
bulkier IPr NHC is more active than IMes (entries 1−4 in
Table 1). In addition, ItBu bearing aliphatic substituents on the
nitrogen atoms exhibits a decreased activity compared to IPr
and IMes. These results can be explained by the greater basicity
of s-IMes, s-IPr, and ItBu which is merely compatible with the
acidity of the amine/CO2 mixture. On the other hand,
introduction of electron withdrawing groups on the imidazo-
lidene ring somewhat deactivates the NHC and 35% 2a is
recovered from morpholine after 1 h at RT with 5 mol % Cl2-
IPr, whereas the yield is quantitative with IPr, demonstrating
that a balance between basicity and nucleophilicity is required
for the NHC catalyst (entries 1 and 5 in Table 1). Overall, IPr
is about 2000 times more active than TBD in the catalytic
formylation of morpholine, using CO2 and PhSiH3, with a RT
turnover frequency (TOF) of 160 h−1 for IPr compared to
0.075 h−1 for TBD.
Having in hand a highly efficient catalytic system, we then
investigated the scope of the reaction for the formylation of a
variety of N−H bonds with PhSiH3 as reductant and IPr as
organocatalyst (Scheme 2). Aliphatic secondary amines, such as
morpholine, piperidine and diethylamine, are converted to their
formamides (2a−2c) quantitatively after 24 h at RT and under
1 bar of CO2. Dimethylformamide (DMF) is obtained as the
only product when dimethylammonium dimethylcarbamate is
employed as a substrate. Interestingly, increasing the steric
congestion at nitrogen does not shut down the reactivity of the
amine and i-Pr2NH is formylated at room temperature with an
excellent 87% yield (2d), whereas 2e is obtained in quantitative
yield from PhMeNH, introducing two aromatic substituents on
the nitrogen atom completely deactivates the reactivity of the
corresponding diphenylamine. Though primary aliphatic
amines proved to be reluctant substrates using nitrogen-bases
as catalysts (e.g., TBD),6 IPr is able to promote the formyla-
tion of benzylamine (87% yield), heptylamine and the bulky
tert-butylamine (99% yield). The same catalyst is also active in
the formylation of aniline derivatives. Interestingly, both N−H
bonds of PhNH2 proved reactive and a mixture of the mono-
(2j, 35%) and bis-formylaniline (2j′, 31%) was recovered after
a
Yields are given with respect to the amine substrate (1).
24 h at RT. Electron donating groups (p-methoxy, p-n-Bu, etc.)
have a positive influence on the conversions observed for
aniline derivatives. On the contrary, p-nitroaniline was found
unreactive under the applied reaction conditions.
The formylation of N−H bonds in less reactive and more
fragile substrates was explored. Formylation of benzophenone
imine is efficient and affords the new formyl derivative 2p in
60% yield, with no reduction of the CN bond. Nonetheless,
(t-Bu)2CNH did not yield 2q and the starting material
was fully recovered after 24 h at RT. Given the mild reac-
tion conditions, functionalization of N−H bonds in hydrazine
(2r, 2s), and hydrazone (2t) derivatives was successfully per-
formed in modest to good yields (>35%), without reduction
of the N−N bond. Similarly, transposition of this strategy to
N-heterocycles provided excellent results when applied to tetra-
hydropyrimidine (2u), imidazole (2v), benzimidazole (2w),
and dimethylpyrazole (2x). Triazole ring systems (2y, 2z)
exhibit a lower reactivity and can be converted to formamides
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Table 2. Organocatalytic Formylation of N−H Bonds Using CO2 and (EtO)3SiH, Ph3SiH, TMDS, and PMHS
a
entry
amine (R1R2NH)
morpholine
organosilane (R3SiH)
n
product
yield [%]
1
Ph3SiH
(EtO)3SiH
TMDS
PMHS
PMHS
PMHS
PMHS
PMHS
PMHS
PMHS
PMHS
PMHS
3
2a
2a
2a
2a
DMF
2g
2i
4
28
43
90
90
67
30
70
83
35
83
29
2
morpholine
3
3
morpholine
1.5
3
4
morpholine
5
0.5[Me2NCO2][Me2NH2]
n-heptyl-NH2
PhCH2NH2
PhCH2NH2
PhNH2
3
6
3
7
3
8
9
2i
9
3
2j
10
11
12
Ph2CNH
3
2p
2r
Ph2NNH2
3
dimethylpyrazole
3
2x
a
Yields are given with respect to the amine substrate (1).
only in low 5−10% yields. Despite the fact that formamides
2a−2z do not have a vast market individually, these results
significantly open the spectrum of chemicals directly available
from CO2.
ASSOCIATED CONTENT
* Supporting Information
Synthesis and characterization of all new compounds, detailed
procedures for catalytic reactions. This material is available free
of charge via the Internet at http://pubs.acs.org.
■
S
Phenylsilane is a mild reductant for CO2 and serves as an
efficient energy source in eqs 1−3. Yet, its cost and reactivity
toward moisture limit further applications of the methodology
for multigram scale applications and, therefore, the impact of
the reaction depicted in eq 3 for large-scale CO2 recycling.
However, within the diagonal approach framework, the
reductant can be modified independently from the functionaliz-
ing reagent (the amine), and we therefore extended the scope
of active organosilanes to less reactive and less expensive silanes
(Table 2).6 Among them, polymethylhydrosiloxane (Me3Si-
(OSiMeH)nOSiMe3, PMHS) is especially attractive for CO2
recycling applications because it is an abundant chemical waste
produced by the silicone industry and it is cost-effective ($2−7
per mole), nontoxic, and moisture stable.8,9 Formylation of
morpholine using CO2 was efficiently performed using Ph3SiH,
(EtO)3SiH, tetramethyldisiloxane (TMDS), and PMHS (en-
tries 1−4, Table 2). As expected, all four silanes exhibit a lower
reactivity than PhSiH3; yet, 2a was isolated with an excellent
90% yield using PMHS.9 Importantly, this reaction is the first
metal-free reduction process utilizing PMHS.10 PMHS is also
active as reducing reagent for the formylation of N−H bonds in
primary and secondary amines, anilines, imines, hydrazines, and
N-heterocycles as attested with the good to excellent yields
obtained in the synthesis of DMF, 2g, 2i, 2j, 2p, 2r, and 2x
(entries 5−12, Table 2). Interestingly, PMHS shows a greater
selectivity than PhSiH3 in the formylation of aniline and 2j is
the only formamide obtained from PhNH2 and PMHS (85%
yield), whereas a mixture of 2j (35%) and 2j′ (31%) is obtained
with PhSiH3.
AUTHOR INFORMATION
Corresponding Author
thibault.cantat@cea.fr
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
For financial support of this work, we acknowledge the CEA,
CNRS, ANR (Fellowship to C.G. and Starting Grant to T.C.),
the FP7 Eurotalents Program (PD Fellowship to O.J.), and the
CEA Physical Sciences Division (PD Fellowship to O.J., Basic
Research on Low Carbon Energies Grant to T.C.).
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