10.1002/cssc.201801037
ChemSusChem
COMMUNICATION
1,4-Dioxane-tuned Catalyst-free Methylation of Amines using CO2
and NaBH4
Zhiqiang Guo,[a,b] Bo Zhang,[b] Xuehong Wei,[a] and Chanjuan Xi*[b]
Abstract: A catalyst-free reductive functionalization of CO2 with
amines and NaBH4 was achieved. This protocol realized the N-
methylation of amines using CO2 as a C1-building block in the 1,4-
dioxane as solvent. Notably, the six-electron reduction of CO2 to the
methyl with formation of C-N bond was attained simultaneously.
reducing reagents. Sodium borohydride (NaBH4), an inexpensive,
ease to handle, and mild reductant, has been rarely reported for
the conversion of CO2 and amines into N-methylated products,
although a reductive formylation of amines with CO2 using NaBH4
as a reductant has been reported by Liu and coworkers.23 Herein,
we report a catalyst-free highly selective methylation of amines
using CO2 and NaBH4. This protocol realized the six-electron
reduction of CO2 to the methyl with the formation of the C-N bond.
The initial optimization studies were explored using N-
methylaniline (1a, 0.5 mmol) as a model substrate. The results
are listed in Table 1. First, the reaction was treated in 1,4-dioxane
solution at atmospheric pressure of CO2 using two equivalents of
NaBH4 as reductant at 100 oC within 24 h, and methylated product,
N,N-dimethylaniline (2a) was obtained in 36% yield along with
trace amount of N-methylformanilide (3a) (entry 1). To improve
the yield, increasing the CO2 pressure to 1 MPa, the yield of 2a
increased to 71% while the 3a was also obtained in 23% yield
(entry 2), the selectivity was significantly reduced. This maybe
owing to high CO2 pressure representing high CO2 concentration
and a large excess of CO2 would consume NaBH4. When
increasing the amount of NaBH4, the yield and selectivity of 2a
increased obviously (entry 3-5), which suggested that the ratio of
CO2 and NaBH4 affects selectivity. Subsequent methylation of 1a
with three equivalents of NaBH4 afforded the desired product 2a
in nearly quantitative yield (98%, entry 4). Then, different solvents
such as dichloroethane (DCE), tetrahydrofuran (THF), acetonitrile,
ethanol, toluene, dimethyl sulfoxide (DMSO) and solvent-free
were screened (entry 6-12), and poor yield and low selectivity
were observed, which indicated that the solvent also play a critical
role on the selectivity and reactivity of the reaction. The 1,4-
dioxane is a best solvent for this reaction. Then, a mixture of
solvent such as different ratio of dioxane and toluene was
Methylamines are important chemicals and core structures
existing in medicines, natural products, dyes, etc.1 Conventionally,
methylamines were prepared by using formaldehyde and
hazardous methylating reagents including methyliodide,
dimethylsulfate or dimethylcarbonate.2 So
a
green and
sustainable methodology for methylamines is desired, and the
reduction of CO2 to methylamines is an alternative and promising
method for recycling CO2 to value-added chemicals due to CO2 is
an attractive, inexpensive, nontoxic and abundant carbon source.
Especially, reductive functionalization of CO2 with amines
provided a straightforward method for construction of carbon-
nitrogen bond.3
Beller’s group 4 and Cantat’s5 reported Ru and Zn catalyst
system for conversion of CO2 and amines into various kinds of N-
methylated products in the presence of hydrosilanes in 2013,
respectively. The methylation of amines via six-electron reduction
of CO2 have been attracted an attention. Many types of catalysts
have been developed to reduce functionalization of CO2 for
methylamines using different reductants. For example, metal-
based catalytic systems including alkaline metal such as cesium,6
inexpensive transition metals (Fe,7 Cu,8 Zn,5 Ni,9), and noble
metals (Ru,4, 10 Pd,11 Pt,12 Au13), as well as organic and inorganic
molecule catalysts, such as N-heterocyclic carbenes,14
carbodicarbene,15 proazaphosphatrane superbases,16 B(C6F5)3,17
TBAF (tetrabutylammonium fluoride),18 glycine betaine,19
carboxylate,6 tungstate20 and so on. It is noteworthy that He’s
group has achieved the hierarchical reduction of CO2 with amine
and hydrosilane to selectively access formamides, aminals, and
methylamines using glycine betaine as catalyst.19a More recently,
Lei and coworkers realized the catalyst-free methylation reactions
of amines with CO2 in the presence of phenylsilane.21 All
mentioned studies adopted dihydrogen and hydrosilanes as
conducted in this protocol (see SI-Table
1 in supporting
information). The results indicated with increasing of amount of
dioxane, the methylated product increased. Furthermore, the
effect of reaction temperature was also examined (entries 13-14),
the best temperature for getting approving yield was 100 oC (entry
4). In addition, we tried to shorten the reaction time, the yield of
2a also decreased (entry 15), notably, the yield over than 90%
can still be obtained.
With the optimized reaction conditions in hand, the scope of
this methylation with various amines was investigated. The
representative results are summarized in Scheme 1. The para-
substituted N-methylanilines with either electron withdrawing or
electron donating groups were tolerated, and the corresponding
N,N-dimethylanilines were obtained over 90% yields (2b-2e, 2f
and 2l). With stronger electron withdrawing group aniline such as
N-methyl-4-(methylformate)aniline, N-methyl-4-cyanoaniline, and
N-methyl-4-nitroaniline, are relatively inert, only giving the desired
[a]
[b]
Dr. Z. Guo, Prof. X. Wei
Scientific Instrument Center
Shanxi University
Taiyuan 030006, P. R. China
B. Zhang, Prof. C. Xi
MOE Key Laboratory of Bioorganic Phosphorus Chemistry &
Chemical Biology, Department of Chemistry
Tsinghua University
Beijing 100084, China
E-mail: cjxi@tsinghua.edu.cn
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
This article is protected by copyright. All rights reserved.