Phosgene-free synthesis of carbamates using co2 and titanium alkoxides

Article abstract of DOI:10.1246/bcsj.20180127

A facile one-pot, phosgene-free method for the synthesis of N-phenylcarbamates is developed. Using this method, various aromatic carbamates could be prepared from aromatic amines, CO₂ and metal alkoxides. Aniline reacted with titanium methoxide (Ti(OMe)₄₎) in the presence of CO₂ (5 MPa) to give methyl N-phenylcarbamate in 85% yield, in 20min. Titanium residue could be regenerated by reaction with dimethyl carbonate at 220 °C for 16 h.

Full text of DOI:10.1246/bcsj.20180127

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Phosgene-free Synthesis of Carbamates Using CO2 and Titanium Alkoxides
Hao-Yu Yuan, Qiao Zhang, Norihisa Fukaya, Xiao-Tao Lin, Tadahiro Fujitani, and Jun-Chul Choi*
Advance Publication on the web July 7, 2018
doi:10.1246/bcsj.20180127
© 2018 The Chemical Society of Japan
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Phosgene-free Synthesis of Carbamates Using CO2 and Titanium Alkoxides
Hao-Yu Yuan,1,2 Qiao Zhang,1 Norihisa Fukaya,1 Xiao-Tao Lin,1,2 Tadahiro Fujitani,1 and Jun-Chul Choi*1,2
1 National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565
2 Tsukuba Research Center for Energy Materials Science (TREMS), Graduate School of Pure and Applied Sciences, University of Tsukuba,
1-1-1, Tennodai, Tsukuba, Ibaraki 305-8573
E-mail: <junchul.choi@aist.go.jp>
Jun-Chul Choi
Jun-Chul Choi received his Ph.D. degree from Tokyo Institute of Technology in 1998 (Prof. Kohtaro Osakada). He joined
the National Institute of Advanced Industrial Science and Technology (AIST) as a JST postdoctoral fellow in 1998.
Currently, he is the leader of Catalyst Design Team at Interdisciplinary Research Center for Catalytic Chemistry at AIST,
and holds the position of Associate Professor at University of Tsukuba. His research interests include the development of
efficient synthetic reactions, especially the utilization of fundamental molecules such as carbon dioxide, hydrocarbons,
and water. He is also interested in designing organic-inorganic hybrid catalysts.
Abstract
A facile one-pot, phosgene-free method for the synthesis of
followed by the reaction with electrophiles, usually alkyl
halides.7 A general problem associated with the direct
conversion of alcohols, amines, and CO2 to carbamates is the
formation of water as the by-product, which must be removed
from the equilibrium reaction. We used nBu2SnO or a nickel
complex as the catalyst and an acetal as the dehydrating agent to
obtain good yields of the amine-based carbamates.8 De Vos et
al.9 reported that bases such as catalysts Cs2CO3, could catalyze
the transformation of an amine and an alcohol into a carbamate
with CO2 as the carbonyl source. Moreover, Tomishige et al.10
developed a method using a heterogeneous CeO2 catalyst for the
one-pot synthesis of organic carbamates from amines, CO2, and
alcohols. However, in this case, only aliphatic amines could be
activated because aromatic amines are poor nucleophiles.11
Therefore, the development of a method for synthesizing
aromatic carbamates from aromatic amines, CO2, and alcohols
is desirable.
N-phenylcarbamates is developed. Using this method, various
aromatic carbamates could be prepared from aromatic amines,
CO2 and metal alkoxides. Aniline reacted with titanium
methoxide (Ti(OMe)4) in the presence of CO2 (5 MPa) to give
methyl N-phenylcarbamate in 85% yield, in 20 min. Titanium
residue could be regenerated by reaction with dimethyl
carbonate at 220 °C for 16 h.
Keywords: CO2, organic carbamates, metal alkoxides
1. Introduction
Polyurethanes (PUs) are commonly used in various
applications such as furniture, bedding, and footwear as well as
in the automotive, medicine, electronics, and construction
industries.1 Furthermore, PUs are next-generation 3D printing
materials. Various 3D printing players are exploring the PU
market and offering innovative solutions, from artificial organs
to fabrics or complex 3D models of machines.2 Pus are
manufactured via the polyaddition of a diol onto a diisocyanate.
The latter is prepared on an industrial scale via the reaction of
the corresponding amines with phosgene, which is a highly toxic
and hazardous reagent.3 Alternative synthesis strategies for PUs
without the use of phosgene have been explored by many
industry and academic researchers. Elimination of alcohol from
carbamates via thermal decomposition is a simple and
convenient method to produce isocyanates.4 Another promising
synthetic route to PUs is transurethanization polycondensation
between a dicarbamate and a diol.5 Hence, most of the studies on
non-phosgene pathways to PUs have aimed at the development
of efficient carbamate processes.
Because of the large-scale depletion of petrochemicals,
renewable resources have gained much attention for sustainable
polyurethane production. The use of the inexpensive and
abundant CO2 as the C1 synthon for synthesizing carbamates
would be viewed as a promising, eco-friendly method.6 Most of
the approaches in this context rely on the production of the
carbamic acid derivatives via the reaction of CO2 and amines,
Scheme 1. Synthetic routes to polyurethanes.
Our group has reported the synthesis of a series of N-
phenylcarbamates from aromatic amines, and, CO2 using
dibutyltin dialkoxides or titanium alkoxides.12 However, because
1

of the low boiling point of MeOH, it is difficult to regenerate
dibutyltin dimethoxide or titanium tetramethoxide from the
residues and MeOH. For this reason, we chose the butylated
carbamate as the final product. However, the decomposition and
transurethanization of methylated dicarbamate were easier than
those of butylated carbamate because MeOH is easily eliminated
by distillation during dealcoholysis.4b-d,5b Synthesis of a
carbamate from an amine, CO2, and silicate ester has also been
reported.13 Herein, we describe an efficient synthesis of
carbamates directly from an amine, CO2, and Ti(OMe)4. Both
aliphatic and aromatic amines could be transformed to the
corresponding carbamates in good yields within 30 min.
Ti(OMe)4 could be regenerated via the reaction between Ti-
containing residues and dimethyl carbonate (DMC) at 220 °C.
filled with CO2 to 3 MPa. The autoclave was heated to 150 °C,
and the pressure of CO2 was adjusted to 5 MPa. After 20 min,
the autoclave was cooled in an ice bath, and CO2 was released
slowly. Toluene (85.3 mg, 0.1 mL) as an internal standard was
added to the mixture. A small amount of the mixture was filtered
for HPLC analysis. The products were separated from the
reaction mixture by vacuum sublimation at 100 °C.
Ti(OMe)4 was regenerated by a method similar to the
preparation of Ti(OEt)4 from TiO2∙xH2O and diethyl carbonate
(DEC).15 Under N2 protection, a mixture of Ti-containing
residue (121 mg) and DMC (5 mL) was introduced into an
autoclave with a stir bar. The autoclave was heated to 220 °C for
16 h. After the reaction, the mixture was transferred into a flask
under N2 atmosphere. DMC and methanol were removed under
reduced pressure to obtain the recovered Ti(OMe)4 (136 mg,
99%).
2. Experimental
Materials
The reaction was conducted in a similar manner using the
recovered Ti(OMe)4 to synthesize carbamates.
The starting compounds NaOMe, Mg(OMe)2, Al(OMe)3,
nBu2Sn(OMe)2, Ti(OMe)4, and Ta(OMe)5 were purchased from
Sigma-Aldrich. Si(OMe)4, Ca(OMe)2, and Ge(OMe)4 were
purchased from Wako Chemicals Co. Cu(OMe)2 and Zn(OMe)2
were purchased from Tokyo Chemical Industry. CO2 was
purchased from Showa Tansan (purity > 99.99%). All the
chemicals were used without further purification.
3. Results and Discussion
Instruments
The catalytic reactions were performed in a 10-mL
stainless-steel autoclave with a gas-pressure monitor (max. 25
MPa). All the moisture-free operations were carried out in a
glovebox. The reaction mixtures were heated in a Sibata Chem-
300 Synthesizer. The product mixtures were analyzed by NMR,
Table 1. Synthesis of carbamates from aniline, CO2 and
various methoxy sources.a
Conv. Yield of 1 Yield of 2
Entry
Reagent
1
HPLC, and GC-MS. H NMR and 13C{1H} NMR spectra were
(%)b
3
(%)b
< 1
< 1
< 1
< 1
1
(%)b
< 1
< 1
< 1
< 1
2
measured on a Bruker AVANCE-III high resolution spectrometer
(400 MHz for 1H). HPLC analyses were conducted using Shim-
pack VP-ODS columns (GL Science) mounted on a Shimadzu
prominence HPLC system equipped with a refractive index
detector (RID). Carbamates were isolated by a Yamazen Al-580
single channel automated flash chromatography system using
ethyl acetate and n-hexane as eluents. All volatile products were
characterized by GC-MS using a Shimadzu GC-2010 gas
chromatograph connected to a GCMS-QP 2010 plus mass
spectrometer.
1
2
MeOH
NaOMe
34
50
2
3
Mg(OMe)2
Al(OMe)3
Si(OMe)4
Ca(OMe)2
Ti(OMe)4
Cu(OMe)2
Zn(OMe)2
Ge(OMe)4
nBu2Sn(OMe)2
Ta(OMe)5
4
5
8
6
33
62
4
< 1
59
< 1
1
7
Typical reaction procedure
Under N2 protection, aniline (75 mg, 0.8 mmol), metal
methoxide (0.8 mmol), and CH3CN (3 mL) were added to an
autoclave equipped with a stir bar. The autoclave was sealed
tightly and filled with CO2 up to a pressure of 3 MPa. The
autoclave was heated to 150 °C, and the pressure of CO2 was
adjusted to 5 MPa. After 20 min, the autoclave was cooled in an
ice bath, and CO2 was released slowly. Toluene (85.3 mg, 0.1
mL) as an internal standard was added to the mixture. A small
amount of the mixture was filtered for HPLC or 1H NMR
analysis. The isolated material was purified by automated flash
chromatography with ethyl acetate and n-hexane as eluents. All
the isolated products listed in Table 4 were characterized by 1H
and 13C{1H} NMR spectroscopy, as well as GC-MS. The data
were consistent with those for authentic materials and literature
values.7g,14
8
< 1
3
< 1
< 1
< 1
4
9
52
1
10
11c
12
< 1
41
47
30
12
< 1
a
Reaction conditions: M(OMe)n (0.8 mmol), aniline (0.8
mmol), CH3CN (3 mL), CO2 (5 MPa), 150 °C. b Determined
by HPLC. c ref. 12a.
In a previous work, nBu2SnO was shown to be very active
for the catalytic activation of CO2, alcohols and aliphatic amines,
giving the corresponding carbamates in good yields and with
high selectivity. Tin alkoxide was the key compound in the
catalystic cycle.8a Therefore, we decided to investigate the
activity of metal alkoxides especially tin alkoxide for the
synthesis of carbamates from amines and CO2. A series of metal
Recycling of Ti(OMe)4 for carbamates synthesis
Under N2 protection, aniline (75 mg, 0.8 mmol), Ti(OMe)4
(138 mg, 0.8 mmol), and CH3CN (3 mL) were added to an
autoclave with a stir bar. The autoclave was sealed tightly and
2

alkoxides were screened for use in the synthesis of carbamates
(Table 1). In the absence of metal alkoxides, no carbamates
formed when MeOH was used as the methoxy-source; this was
because of thermodynamic limitations and the poor nucleophilic
properties of aromatic amines (Table 1, entry 1). Among the
metal alkoxides tested, Ti(OMe)4 and nBu2Sn(OMe)2 exhibited
relatively higher activity for carbamate synthesis. In the presence
of Ti(OMe)4, the desired product methyl N-phenylcarbamate 1
was obtained in modest yield (59%) and 1% N,N’-diphenylurea
2 was formed as the minor product (Table 1, entry 7).
Various solvents were applied for this reaction; the results
are shown in Table 2. Similar results were obtained when using
1,4-dioxane, tetrahydrofuran (THF), CH2Cl2, or ethyl ether as
the solvent (entries 1-4). No carbamate was obtained when using
alcohol as the solvent, because of the formation of DMC as the
main product. With acetonitrile as the solvent, the conversion
was 65% and the yield of carbamate reached 61% (entry 5).
increased even after 60 min of reaction at 180 °C. The reaction
conducted at a higher temperature of 200 °C for 10 min gave
87% carbamate yield, which was similar to the yield obtained at
180 °C. However, a lower carbamate yield was observed upon
increasing the reaction time beyond 20 min because of the
reaction of aniline and carbamate to give, urea as the side product
(See Supporting Information Scheme S2). The optimal reaction
temperature was determined to be 180 °C for a reaction time of
20 min.
CO2 pressure-dependent plots of carbamate synthesis from
aniline, CO2, and Ti(OMe)4 are shown in Figure 2. The yield of
carbamate increased with increasing CO2 pressure from 1 MPa
to 5 MPa, and remained almost unchanged, above 5 MPa. CO2
insertion into a M-O bond is reported to occur very easily even
under low CO2 pressure at room temperature.16 Because metal
carbonates, which are products of CO2 insertion, are
thermolabile, high CO2 pressures are required to shift the
reaction equilibrium to the product side at the given reaction
temperature. The formation of urea depends on the aniline
concentration and carbamate concentration in the reaction
mixture. Thus, the low aniline conversion at 1 MPa CO2 pressure
leads to a higher yield of urea (9%). When the CO2 pressure was
raised to 9 MPa, the yield of urea decreased to 1%.
Table 2. Synthesis of carbamates from aniline, CO2, and
Ti(OMe)4 in various solvents.a
Conv. Yield of 1
Yield of 2
Entry
Solvent
(%)b
48
(%)b
47
(%)b
< 1
< 1
1
1
2
3
4
5
6
THF
1,4-dioxane
CH2Cl2
50
50
48
46
ethyl ether
CH3CN
51
47
1
65
61
1
MeOH
< 1
< 1
< 1
a
Reaction conditions: aniline (0.8 mmol), Ti(OMe)4 (0.8
b
mmol), CO2 (5 MPa), solvent (3 mL), 150 °C, 20 min.
Determined by HPLC.
Figure 2. Effect of CO2 pressure on carbamate synthesis from
aniline, CO2, and Ti(OMe)4. Reaction conditions: aniline (0.8
mmol), Ti(OMe)4 (0.8 mmol), CO2, CH3CN (3 mL), 180 °C, 20
min.
With the optimized reaction conditions (0.8 mmol amine,
0.8 mmol Ti(OMe)4, 5 MPa CO2, 3 mL CH3CN at 150 °C for 30
min) in hand, we next investigated the substrate scope. 1H NMR
spectra and GC-MS studies showed that various substituted aryl
and alkyl carbamates could be obtained from the corresponding
amines (Table 3) by this method. Aromatic amines with an
electron-donating group (Table 3, entries 2 and 7) gave higher
yields of the corresponding carbamates than those with an
electron-withdrawing group (Table 3, entries 3-6). The effect of
electron-donating groups on the electrophilic aromatic
substitution can result in a negative charge to the nitrogen atom
of the -NH2 group, thus promoting carbamate formation. The
reactivity of the substituted aromatic amines employed in this
reaction decreased in the order para > meta > ortho, which was
ascribed to the increased steric hindrance. Only the amino group
was activated, while other functional groups such as methoxy,
methyl, halo, nitro, and cyano were unreactive; this made our
protocol a chemoselective method for carbamate synthesis.
Electron-enriched aliphatic amines also gave good yield of the
corresponding carbamates. After 20 min, cyclohexylamine and
tert-butylamine were converted to the corresponding carbamates
in 88% and 81% yields, respectively.
Figure 1. Effect of temperature on carbamate synthesis from
aniline, CO2, and Ti(OMe)4. Reaction conditions: aniline (0.8
mmol), Ti(OMe)4 (0.8 mmol), CO2 (5 MPa), CH3CN (3 mL).
The yield of carbamate was determined by HPLC. The yield of
urea is omitted for clarity.
Figure 1 illustrates the effect of temperature on the yield of
carbamate. High temperatures (>100 °C) are necessary for
carbamate synthesis directly from aniline, CO2, and Ti(OMe)4.
At 150 °C, the yield of carbamate increased upon prolonging the
reaction, and reached 71% at 60 min. The formation of
carbamate at 180 °C was rapid in the initial stage and reached
the maximum at 20 min. The yield of carbamate could not be
3

methyl-, bromo-, and nitro-substituted aniline were conducted
for the Hammett studies. A linear relationship and a negative
slope (ρ = -1.0232) were obtained, indicating the electrophilic
nature of the titanium carbonate species attacked by the
nucleophilic amines.
H
Ti(OMe)4 (0.8 mmol)
CH3CN, 180 oC, 20 min
N
OMe
R
NH2
+ CO2
R
O
Table 3. Carbamate synthesis using various amines.a
Entry
amine
Conv. (%)b
Yield (%)b
CO2 (5 MPa)
Ti(OMe)4 (0.8 mmol)
NH2
NHCOOMe
(a)
(b)
1
86
85 (83)
180 oC, 60 min
NH2
(0.4 mmol)
NHCOOMe
1l
(
, Isolated yield = 60%)
2
3
97
84
55
66
64
99
88
65
95
99
95 (92)
82 (77)
54 (50)
62 (60)
61 (55)
99 (98)
85 (81)
65 (61)
93 (88)
90 (81)
CO2 (5 MPa)
Ti(OMe)4 (0.8 mmol)
180 oC, 20 min
NH2
H2N
(0.4 mmol)
MeOOCHN
NHCOOMe
4
1m
(
, Isolated yield = 82%)
Scheme 2. Synthesis of dicarbamate (polyurethane precursor)
with industrial application.
5
6
7
8
Figure 3. Hammett analysis of carbamate synthesis from para-
substituted aniline. Reactions conditions: para-substituted
aniline (OMe, Me, H, Cl, CN) (0.8 mmol), Ti(OMe)4 (0.8 mmol),
CH3CN (3 mL), CO2 (5 MPa), 120 °C, 20 min.
9
10
11
We have reported that it is easy to regenerate Ti(OnBu)4 by
reaction with nBuOH during the removal of water by azeotropic
distillation (Table 4, entry 2).12b However, it is difficult to
regenerate Ti(OMe)4 in this manner because the boiling point of
MeOH is much lower than that of water, which leads to
difficulties in the removal of water from the reaction mixture.
Ono and coworkers reported a very useful method to obtain
titanium tetraalkoxides in almost quantitative yields by the
reaction of aqueous titanium dioxide with dialkyl carbonates.15
After the carbamate synthesis, aniline, carbamate, urea,
and acetonitrile were distilled out from the reaction mixture,
leaving behind Ti-containing residues. The Ti-containing
residues were then converted into Ti(OMe)4 in the presence of
DMC and excess methanol at 220 °C for 16 h. After regeneration,
all the volatiles were distilled out, leaving behind a colorless oil
identified as Ti(OMe)4. Then, aniline was added to the recovered
Ti(OMe)4, and the autoclave was pressurized with CO2. The
yield of carbamate obtained using the recovered Ti(OMe)4 was
86% after 20 min, which was the same as that obtained using
fresh Ti(OMe)4. Ti(OMe)4 showed the same level of
recyclability as Ti(OnBu)4. This result indicates that Ti(OMe)4
can be reused without loss of activity and hence finds potential
application in industrial processes.
a
Reaction conditions: amine (0.8 mmol), Ti(OMe)4 (0.8
b
mmol), CO2 (5 MPa), CH3CN (3 mL), 180 °C, 20 min.
Determined by 1H NMR, isolated yields are given in
parentheses.
Our research highlights the activation of 2,4-diamino-
toluene (DAT) and 4,4'-methylenedianiline (MDA) to produce a
dicarbamate required for the polyurethane industry. In the case
of 2,4-DAT (Scheme 2a), we achieved a high conversion of 2,4-
DAT (93%) with a modest yield of the desired product 1l (60%),
and a significant amount of monocarbamoylated products (33%)
was formed after 1 h of reaction at 180 °C. In this case of 4,4'-
MDA (Scheme 2b), 1m was obtained in 82% yield after 20 min,
along with trace amounts of the monocarbamoylated product.
The results of substrate scope indicated a relationship
between the carbamate yield and the electronic properties of the
substituent on aniline. The relevant Hammett plot is shown in
Figure 3. Several competing reactions involving methoxy-,
4

1999, 14, 67. (c) Z. S. Petrovic, Polym. Rev. 2008, 48, 109.
(d) O. Kreye, H. Mutlu, M. A. R. Meier, Green Chem. 2013,
15, 1431.
2.
(a) A. Pfister, R. Landers, A. Laib, U. Hübner, R.
Schmelzeisen, R. Mülhaupt, J. Polym. Sci. A. Polym.
Chem. 2004, 42, 624. (b) K.-C. Hung, C.-S. Tseng, S.-H.
Hsu., Adv. Healthc. Mater. 2014, 3, 1578. (c). K.-C. Hung,
C.-S. Tseng, L.-G. Dai, S.-H. Hsu, Biomaterials 2016, 83,
156.
Table 4. Recycling of Ti(OR)4 for carbamate synthesis.a
Yield of 1 (%)a
Entr
3.
4.
(a) R. L. Shriner, W. H. Horne, R. F. B. Cox, Org. Synth.
1943, 2, 453. (b) R. J. Slocombe, E. E. Hardy, J. H.
Saunders, R. L. Jenkins, J. Am. Chem. Soc. 1950, 72, 1888.
(a) O. Bayer, Angew. Chem. 1947, 59, 257. (b) E. Dyer, G.
C. Wright, J. Am. Chem. Soc. 1958, 81, 2138. (c) E. Dyer,
G. E. Newborn, J. Am. Chem. Soc. 1958, 80, 5495. (d) P.
Uriz, M. Serra, P. Salagre, S. Castillon, C. Claver, E.
Fernandez, Tetrahedron Lett. 2002, 43, 1673. (e) D. C. D.
Butler, H. Alper, Chem. Commun. 1998, 2575.
Ti(OR)4
y
Fresh
85
Recycled
1
Ti(OMe)4
86
84
2b
Ti(OnBu)4
84
a
Reaction conditions: aniline (0.8 mmol), Ti(OMe)4 (0.8
mmol), CO2 (5 MPa), CH3CN (3 mL), 180 °C, 20 min. b ref.
12b.
5.
6.
(a) L. Maisonneuve, O. Lamarzelle, E. Rix, E. Grau, H.
Gramail, Chem. Rev. 2015, 115, 12407. (b) H. Sardon, A.
Pascual, D. Mecerreyes, D. Taton, H. Gramail, J. L.
Hedrick, Macromolecules 2015, 48, 3153.
(a) T. Sakakura, J.-C. Choi, H. Yasuda, Chem. Rev. 2007,
107, 2365. (b) D. Chaturvedi, Tetrahedon 2012, 68, 15. (c)
H. Blattmann, M. Fleischer, M. Bähr, R. Mülhaupt,
Macromol. Rapid Commum. 2014, 35, 1238. (d) R. H.
Heyn, I. Jacobs, R. H. Carr, Adv. Inorg. Chem. 2014, 66,
83.
Several reaction mechanisms for carbamate formation
from RNH2 + CO2 + MOR’ have been proposed.12,16a When
Ti(OnBu)4 is used, it typically reacts with CO2 to produce a
titanium carbonate complex as the reaction intermediate. In our
case, CO2 insertion into a Ti-O bond of Ti(OMe)4 occurs in the
same manner (eq. 1).
7.
(a) Y. Yoshida, S. Ishii, T. Yamashita, Chem. Lett. 1984, 9,
1571. (b) Y. Yoshida, S. Ishii, M. Watanabe, T. Yamashita,
Bull. Chem. Soc. Jpn. 1989, 62, 1534. (c) W. McGhee, D.
Riley, K. Christ, Y. Pan, B. Parnas, J. Org. Chem. 1995, 60,
2820. (d) M. Yoshida, N. Hara, S. Okuyama, Chem.
Commun. 2000, 151. (e) R. Srivastava, M. D. Manju, D.
Srinivas, P. Ratnasamy, Catal. Lett. 2004, 97, 41. (f) J. M.
Hooker, A. T. Reibel, S. M. Hill, M. J. Schueller, J. S.
Fowler, Angew. Chem. Int. Ed. 2009, 48, 3482; (g) D.
Riemer, P. Hirapara, S. Das, ChemSusChem 2016, 9, 1916.
(a) M. Abla, J.-C. Choi, T. Sakakura, Chem. Commun.
2001, 2238. (b) M. Abla, J.-C. Choi, T. Sakakura, Green
Chem. 2004, 6, 524.
The results of Hammett analysis indicate that the
nucleophilic attack of the amine nitrogen on the carbon atom
derived from CO2 insertion generates the carbamate (eq. 2).
8.
9.
4. Conclusion
In summary, we have developed an efficient method for the
direct synthesis of carbamates from amines, CO2, and Ti(OMe)4.
Notably, this reaction is chemoselective toward amine activation.
Ti(OMe)4 can be regenerated by a reaction with DMC at 220 °C.
This methodology opens up a new route for the production of
organic carbamates, especially aromatic carbamates, which are
important precursors for PUs. A tentative mechanism for this
reaction is proposed, and the negative ρ value determined by
Hammett analysis indicates nucleophilic attack of the amine
onto the Ti carbonyl species derived from Ti(OMe)4 and CO2.
A. Ion, C. V. Doorslaer, V. Parvulescu, P. Jacobs, D. D. Vos,
Green Chem. 2008, 10, 111.
10. (a) M. Honda, S. Sonehara, H. Yasuda, Y. Nakagawa, K.
Tomishige, Green Chem. 2011, 13, 3406. (b) M. Tamura,
M. Honda, K. Noro, Y. Nakagawa, K. Tomishige, J. Catal.,
2013, 305, 191. (c) M.Tamura, M. Honda, Y. Nakagawa,
K. Tomishige, J. Chem. Technol. Biotechnol. 2014, 89, 19.
11. (a) T. Jiang, X. Ma, Y. Zhou, S. Liang, J. Zhang, B. Han,
Green. Chem. 2008, 10, 465. (b) W. Guo, J. Gonzalez-
Fabra, N. A. G. Bandeira, C. Bo, A. W. Kleij, Angew. Chem.
Int. Ed. 2015, 54, 11686.
12. (a) H.-Y. Yuan, J.-C. Choi, S.-y. Onozawa, N. Fukaya. S. J.
Choi, H. Yasuda, T. Sakakura, J. CO2 Util. 2016, 16, 282.
(b) J.-C. Choi, H.-Y. Yuan, N. Fukaya, S.-y. Onozawa, Q.
Zhang, S. J. Choi, H. Yasuda, Chem. Asian J. 2017, 12,
1297.
13. (a) Q. Zhang, H.-Y. Yuan, N. Fukaya, J.-C. Choi,
ChemSusChem 2017, 10, 1501. (b) Q. Zhang, H.-Y. Yuan,
N. Fukaya, H. Yasuda, J.-C. Choi, Green Chem. 2017, 19,
5614. (c) Q. Zhang, H.-Y. Yuan, N. Fukaya, J.-C. Choi,
ACS Sustainable Chem. Eng. 2018, 6, 6675.
14. (a) J. Holt, T. Andreassen, J.M. Bakke, A. Fiksdahl, J.
Heterocycl. Chem. 2005, 42, 259. (b) Q. Yang, A.
Robertson, H. Alper, Org. Lett. 2008, 10, 5079. (c) M.
Hutchby, C. E. Houlden, J. G. Ford, S. N. G. Tyler, M. R.
Acknowledgement
This research was supported in part by a grant (No.
P16010) from the New Energy and Industrial Technology
Development Organization (NEDO).
Supporting Information
Analytical data, NMR and MS data for compounds 1a-1m.
This material is available on http://dx.doi.org/10.1246/ bcsj.xxx.
References
1.
(a) T. Thomson, in polyurethanes as specialty chemicals:
Principles and applications, CRC Press, Boca Raton, FL,
2004. (b) R. J. Zdrahala, I. J. Zdrahala, J. Biomater. Appl.
5

Gagne, G. C. Lloyd-Jones, K. I. Booker-Milburn. Angew.
Chem. Int. Ed. 2009, 48, 8721. (d) X. Zhang, H. Jing, G.
Zhang, Synth. Commun. 2010, 40, 1614. (e) A. Yoshimura,
M. W. Luedtke, V. V. Zhdankin, J. Org. Chem. 2012, 77,
2087.
15. E. Suzuki, S. Kusano. H. Hatayama, M. Okamoto, Y. Ono,
J. Mater. Chem. 1997, 7, 2049.
16. (a) A. J. Goodsel, G. J. Blyholdes, J. Am. Chem. Soc. 1972,
94, 6725. (b) T. Tsuda, S. Sanoda, K. Ueda, T. Saegusa,
Inorg. Chem. 1976, 15, 2329. (c) T. Aida, S. Inoue, J. Am.
Chem. Soc. 1983, 105, 1304. (d) J.-C. Choi, T. Sakakura,
T. Sako, J. Am. Chem. Soc. 1999, 121, 3793. (e) M. M.
Ibrahim, K. Ichikawa, M. Shiro, Inorg. Chem. Commun.
2003, 6, 1030. (f) F. Parrino, C. Deiana, M. R. Chierotti, G.
Martra, L. Palmisano, J. CO2 Util. 2016, 13, 90.
6