Carbonylative coupling of: N -chloroamines with alcohols: Synthesis of esterification reagents

Article abstract of DOI:10.1039/c8ob00462e

Herein we report a new method for the carbonylative synthesis of carbamates. Starting from N-chloroamines and alcohols, with copper or Pd/C as the catalyst, the corresponding carbamates were produced in moderate to good yields. No additional oxidant or base is needed in this system. Notably, the produced benzotriazole-carboxylates can be used as esterification reagents.

Full text of DOI:10.1039/c8ob00462e

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DOI: 10.1039/C8OB00462E
Carbonylative Coupling of N-Chloroamines with Alcohols: Synthesis
of Esterification Reagents
Zhiping Yin, Zechao Wang, and Xiao-Feng Wu*a
Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Straße 29a, 18059 Rostock, Germany, E-mail:
xiao-feng.wu@catalysis.de
ABSTRACT: Herein we report a new method for the car-
bonylative synthesis of carbamates. Started from N-
chloroamines and alcohols, with copper or Pd/C as the cata-
lyst, the corresponding carbamates were produced in moder-
ate to good yields. No additional oxidant or base is needed in
this system. Notably, the produced benzotriazole-
carboxylates can be used as esterification reagent.
The chemistry of N-chloroamines recently has attracted a
great deal of attention, since it is an important building block
for the synthesis of different nitrogen containing compounds
(Scheme 1).1 For example, the research groups led by Glorius
and Yu reported a rhodium catalyzed intermolecular C-H
Scheme 1. N-Chloroamines based organic reactions.
amination reaction of arenes with N-chloroamines, inde-
pendently.2 In 2014, Nakamura’s group developed the ortho-
On the other hand, oxidative carbonylation reactions are
an efficient method to produce various carbonyl derivative
products from two nucleophiles.9 Generally, besides catalysts
and additives, the process is consisted by two nucleophiles
and an oxidant. Concerning the oxidants, organic com-
pounds or inorganic salts, including benzoquinone (BQ),
potassium persulfate (K2S2O8), copper and silver salts, and air
or oxygen are commonly applied. However, the selectivity of
oxidative carbonylation reactions usually is problematic,
especially when the two nucleophiles are different. There-
fore, it is interesting to continual to develop new and selec-
tive oxidative carbonylation procedures. Among the various
possibilities, N-chloroamine is an ideal choice which can be
used as both the substrate and oxidant. In this manner, a
selective carbonylation procedure without additional oxidant
can be established (Scheme 2).
amination of aromatic carboxamides in the presence of an
iron/diphosphine catalyst.3 Besides, electrophilic amination
catalyzed by nickel, copper or cobalt was also reported by
Jarvo’s, Murakami’s and Gosmini’s groups respectively, which
gives an efficient method for the construction of carbon-
nitrogen bonds.4 Furthermore, nitrogen radical generated
from N-chloroamines can react with different functional
groups such as, aldehyde5 or intramolecular double bond6
were also reported. Our group studied the carbonylative
coupling of aryl boronic acids with N-chloroamines as
well.7a,7b Benzamides can be produced in an efficient manner.
Simandi’s group reported a palladium-catalyzed carbonyla-
tion of alkali metal salts of N-chloroarylsulfonamides with
R'XH (X=O, S, NR') to give arylsulfonylcarbamic acid esters,
thioesters, and amides.7c Very recently J. Wu and co-workers
reported a copper catalyzed coupling reaction of aryl diazo-
nium salts, SO2 and N-chloroamines to produce aromatic
sulfonamides.8
Scheme 2. Oxidative carbonylation reactions.
The reaction was initially performed using 1-chloro-1H-
benzo[d][1,2,3]triazole 1a as the model substrate to establish
the reaction conditions. The first reaction was conducted

Organic & Biomolecular Chemistry
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DOI: 10.1039/C8OB00462E
0%
with 1a (2.0 equiv.) and methanol (1.0 equiv.) in CH3CN in
[(iPr)CuCl]
[(iPr)CuCl]
[(iPr)CuCl]
H2O
18
19
20
79%[h]
the presence of CuCl2 (5 mol%) under 50 bar CO pressure at
70 °C. To our delight, the reaction yielded 13% of the desired
product (Table 1, entry 1). Then different catalysts were
screened, the yield was increased to 64% when bromo(1,10-
phenanthroline)(triphenylphosphine)copper(I) was applied
as the catalyst (Table 1, entry 8). In the testing with Fe2(CO)8
and Pd/C (Table 1, entries 5-7), 68% of the desired product
can be produced with Pd/C and tetra-N-butylammonium
bromide (TBAB) as the catalytic system (Table 1, entry 7).
Based on our previous experience with N-chloroamines,7 the
addition of base might can improve the reaction outcome.
We therefore added 1 equivalent of base in the reaction mix-
ture. However, only trace product was detected in the GC
MeCN
80%[i]
MeCN
[a]
Reaction scale: catalyst (5 mol%), 1 mmol 1a (2 eq.), 0.5 mmol
[b]
MeOH, 50 bar CO, solvent (1.0 mL), 70 °C, 16 hours.
GC yields
were determined by using hexadecane as the internal standard. [c] 1.0
eq NaHCO3 was added. [d] 1.0 eq pyridine was added. [e] Isolated yield.
[f] [(iPr)CuCl] (2.5 mol%). [g] 1.5 eq 1a instead of 2.0 eq 1a. [h] 30 bar
CO. [i] 60 °C. [(iPr)CuCl] = [1,3-bis(2,6-diisopropylphenyl)imidazol-2-
ylidene]copper(I) chloride. THF = Tetrahydrofuran. DMF = dime-
thylformamide. DCE = 1,2-dichloroethane.
Having determined the best conditions, we next examined
the scope of this reaction with a range of alcohols and N-
chloroamines. As show in Table 2, we first examined the
substrate of alcohols with 1-chloro-1H-benzo[d][1,2,3]triazole
1a. Various benzotriazole-carboxylates were formed in mod-
erate to good yields. A series of alcohols including ethanol,
butanol and 3-phenylpropanol were well tolerated under the
optimal conditions (Table 2, entries 2, 3 and 6). Remarkably,
cyclobutylmethanol and cyclohexylmethanol were also suc-
cessfully delivered the desired products in 55% and 68%
yield, respectively (Table 2, entries 8 and 9). Benzyl alcohol
and secondary alcohol were failed to generate the desired
product as they are easier to be oxidized (Table 2, entries 10
and 11).
(Table 1, entries
9 and 10) which suggests that N-
chloroamines might be unstable under basic conditions.10
Finally, the yield was improved to 85% (Table 1, entry 11; 80%
isolated yield) when CuCl(iPr) (5 mol%) [(iPr)CuCl = [1,3-
bis(2,6-diisopropylphenyl)imidazol-2-ylidene]copper(I) chlo-
ride] was utilized as the catalyst for this reaction. Reducing
the loading of catalyst or 1a, decreasing the yield to 76% and
56% respectively (Table 1, entries 12-13). Alternative solvents,
including THF, DMF, toluene, DCE and H2O were tested
subsequently (Table 1, entries 14-18), all of these solvents are
inferior to CH3CN. The reaction efficiency slightly dropped
with lower temperature or CO pressure (Table 1, entries 19-
20). The final optimized conditions were found to be:
CuCl(iPr) (5 mol%) at 70 °C which gave 2a in 80 % isolated
yield (Table 1, entry 11).
Table 2. Scope of alcohols and N-chloroamines [a]
.
Table 1. Optimization of the reaction conditions.[a]
Yield[b]
Catalysts
CuCl2
Solvent
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
Entry
13%
30%
1
2
CuI
12%
Cu(OAc)2
3
14%
Cu(TC)
4
14%
Fe2(CO)8
5
52%
Pd/C
6
68%
Pd/C, TBAB (5 mol%)
CuBr(PPh3)(1,10-Phen)
CuBr(PPh3)(1,10-Phen)
CuBr(PPh3)(1,10-Phen)
7
64%
8
Trace[c]
7%[d]
9
10
85%
80%[e]
[(iPr)CuCl]
MeCN
11
76%[f]
56%[g]
0%
[(iPr)CuCl]
[(iPr)CuCl]
[(iPr)CuCl]
[(iPr)CuCl]
[(iPr)CuCl]
[(iPr)CuCl]
MeCN
MeCN
THF
12
13
14
15
16
17
trace
15%
31%
DMF
Toluene
DCE
2

Page 3 of 4
Organic & Biomolecular Chemistry
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DOI: 10.1039/C8OB00462E
O
and 13). Here the mixture of two products is due to the sub-
strates were prepared as a difficult to separate mixture and
were used directly.
Cl
OR2
N
N
[(iPr)CuCl] (5 mol%)
CH3CN, 70 °C, 16 h
R1
CO + R2OH
R1
N
+
N
N
N
Additionally, other types of secondary N-chloroamines
were also tested. As shown in Table 3, various N-chloroamine
substrates were synthesized according to the reported proce-
dure and reacted smoothly.12 It is noteworthy that Pd/C is a
more efficient catalyst in this reaction compared with copper
catalyst (45% yield of product under the above conditions).
Various carbamate products were obtained in moderate to
good yields. In addition, except for methanol, other alcohols,
such as 3-phenylpropanol and 2,2,2-trifluoroethanol were
also participated successfully, leading to the desired products
in moderate yields (Table 3, entries 3-5).
2a
1a
Entry
Substrate
Product
Yield
O
OR
2a
2b
2c
1
2
3
R = Me 80%
R = Et 79%
R = n-Bu 72%
1a
+
ROH
2a
N
N
N
O
O
4
5
1a
1a
+
HO
2d
73%
67%
N
N
N
O
O
+
2e
HO
N
Ph
Ph
N
N
Table 3 Scope of N-chloroamines [a]
.
O
O
6
7
1a
1a
+
C6H5(CH2)3OH
C6H5(CH2)4OH
2f
83%
Ph
N
N
N
O
O
+
2g
66%
55%
68%
N
N
N
Ph
O
O
8
9
1a
1a
+
2h
HO
HO
N
N
N
O
O
+
2i
N
N
N
O
O
Ph
2j
HO
HO
Ph
1a
1a
+
10
11
0%
N
N
N
O
O
2k
Ph
+
N
0%
Ph
N
N
Cl
O
O
O
Cl
N
Cl
2l
N
N
1b
N
N
N
N
O
+
MeOH
[a] Reaction scale: Pd/C (2 mol%, 21.2 mg), TBAB (5 mol%,
Cl
70%
12
N
1b'
16.3 mg), 1d, 1e (1.0 mmol), R3OH (10 mmol), 50 bar CO,
N
2l'
N
N
[b]
N
Cl
MeCN (2.0 mL), 70 °C, 16 hours, isolated yield.
Pd/C (2
Cl
mol%, 21.2 mg), TBAB (5 mol%, 16.3 mg), 1f, 1g (1.0 mmol),
ROH (2 mmol), 50 bar CO, MeCN (2.0 mL), 70 °C, 16 hours.
TBAB = tetra-N-butylammonium bromide.
Cl
O
O
O
Br
N
Br
N
N
N
N
N
1c
N
2m
13
Next, we turned our attention to investigate the application
of our produced benzotriazole-carboxylates. According to
the literature reported by Cava and co-workers, they used
their prepared 1H-benzo[d][1,2,3]triazole-1-carbonitrile as a
cyanation reagent to react with arylacetonitrile anions to give
the corresponding arylmalonitriles products.13 Therefore, we
hypothesize that our benzotriazole-carboxylates can be used
as an alkoxycarbonylation reagent (esterification reagent) as
well. Delightfully, after using 2a to react with phenylacetoni-
trile in the LDA/THF condition, the desired product methyl
(S)-2-cyano-2-phenylacetate was formed in 74% yield
+
MeOH
Cl
77%
O
N
1c'
N
2m'
N
N
N
Br
Br
[a]
Reaction scale: 1a-1c (1.0 mmol, 153 mg), [(iPr)CuCl] (5
mmol%, 12 mg), R2OH (0.5 mmol), 50 bar CO, solvent (2.0 mL),
70 °C, 16 hours, isolated yield.
Furthermore, various 1-chloro-1H-benzo[d][1,2,3]triazole
bearing halogen substitutes on the aromatic rings engaged in
this reaction efficiently,11 potentially providing a synthetic
handle for further synthetic modifications (Table 2, entries 12
3

Organic & Biomolecular Chemistry
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DOI: 10.1039/C8OB00462E
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Scheme 3. Synthetic application.
Based on previous reports,2-8 a possible reaction mecha-
nism is proposed (Scheme 4). Firstly, dialkylaminyl copper A
is generated by oxidative addition from the N-choro dialkyl-
amine to the Cu(I). Under high pressure of carbon monoxide,
CO is inserted into the dialkylaminyl copper intermediate to
form carbamoyl copper B, which undergoes X ligand transfer
with alcohols to form the product-releasing intermediate C.
Then intermediate C affords the final carbamate products
after reductive elimination while the active Cu(I) species is
regenerated for the next catalytic cycle.
(11) J. Fu, Y. Yang, X.-W. Zhang, W.-J. Mao, Z.-M. Zhang, H.-L.Zhu,
Bioorgan. Med. Chem. 2010, 18, 8457.
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Bertrand, H. Vogel, M. Goeldner, R. Hovius, Angew. Chem. Int. Ed. 2007,
46, 3505.
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401.
Scheme 4. Proposed mechanism.
In conclusion, a novel and versatile protocol for carbonyla-
tive transformation of N-chloroamines with alcohols have
been developed. With copper or palladium on carbon as the
catalysts, various benzotriazole-carboxylates and carbamates
were produced in moderate to good yields with excellent
functional group tolerance. Notably, the obtained products
can be applied as an esterification reagent.
Conflict of interest
The authors declare no conflict of interest.
ACKNOWLEDGMENT
The analytic supports of Dr. W. Baumann, Dr. C. Fisher, S. Buchholz,
and S. Schareina are gratefully acknowledged. We also appreciate the
general supports from Professors Matthias Beller and Armin Börner
in LIKAT.
REFERENCES
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