New method of synthesizing N-alkoxycarbonyl-N-arylamide with triphosgene

Article abstract of DOI:10.1080/00397910600764675

N-Chloroformyl-N-arylcarbamate, the key intermediate for the synthesis of some excellent pesticides, was synthesized through a new method with triphosgene instead of toxic phosgene. It cannot be obtained through the traditional method using triethylamine as a nucleophile. When triethylamine was replaced by a stronger base, sodium hydride, the product was obtained in good yield. Copyright Taylor & Francis Group, LLC.

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New Method of Synthesizing
N‐Alkoxycarbonyl‐N‐arylamide with
Triphosgene
Yuhan Zhou a , Runjun Gong a & Weirong Miao a
a State Key Laboratory of Fine Chemicals , Dalian University of Technology ,
Dalian, China
Published online: 16 Feb 2007.
To cite this article: Yuhan Zhou , Runjun Gong & Weirong Miao (2006) New Method of Synthesizing
N‐Alkoxycarbonyl‐N‐arylamide with Triphosgene, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 36:18, 2661-2666, DOI: 10.1080/00397910600764675
To link to this article: http://dx.doi.org/10.1080/00397910600764675
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Synthetic Communicationsw, 36: 2661–2666, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600764675
New Method of Synthesizing
N-Alkoxycarbonyl-N-arylamide
with Triphosgene
Yuhan Zhou, Runjun Gong, and Weirong Miao
State Key Laboratory of Fine Chemicals, Dalian University of
Technology, Dalian, China
Abstract: N-Chloroformyl-N-arylcarbamate, the key intermediate for the synthesis of
some excellent pesticides, was synthesized through a new method with triphosgene
instead of toxic phosgene. It cannot be obtained through the traditional method
using triethylamine as a nucleophile. When triethylamine was replaced by a stronger
base, sodium hydride, the product was obtained in good yield.
Keywords: Chlorocarbonylation, N-chloroformyl-N-arylcarbamate, triphosgene
INTRODUCTION
Indoxacard (DPX-JW062, JW062) is a new oxadiazine insecticide introduced
by the E. I. DuPont Company that has shown outstanding field activity,
environmental compatibility, and safety to nontarget organisms.[1] Besides
Indoxacard, many compounds with condensed bicyclic or tricyclic structure
were studied, and many of them showed good insecticidal activity to lepidop-
teran larvae.[2]
Most of the analogous insecticides have an N-alkoxycarbonyl-N-
arylamide side chain, which can be introduced by N-chloroformly-N-aryl-
carbamate. The preparation of N-chloroformyl-N-arylcarbamate is very
important in the synthesis of such insecticides. N-Chloroformyl-N-
Received in R.O.C. September 1, 2005
Address correspondence to Yuhan Zhou, State Key Laboratory of Fine Chemicals,
Dalian University of Technology, Dalian 116012, China. E-mail: zhouyh@dl.cn
2661

2662
Y. Zhou, R. Gong, and W. Miao
arylcarbamate was obtained through the chlorocarbonylation of N-arylcarba-
mate with phosgene.[3] However, phosgene is a toxic gas and easy to
diffuse, which makes the syntheses potentially hazardous.
Over the past few years triphosgene [bis(trichloromethyl)-carbonate,
BTC] has emerged as a versatile synthetic reagent for the synthesis of a
large variety of organic compounds.[4] Compared with phosgene, BTC is
not only safer to use and more conveniently handled, transported, and
stored, but in addition, being a solid, it can be weighed exactly. Reactions
using this reagent are normally carried out under mild conditions and afford
and afford good to excellent yields. This white crystalline compound has
now replaced its gaseous congener phosgene.
RESULTS AND DISCUSSION
In most cases using triphosgene, a nucleophile, usually a tertiay amine (triethyl-
amine, pyridine, etc.), is demanded for the generation of phosgene in situ.[5] To
our surprise, no product was found when we followed the traditional method
using triethylamine as the nucleophile. However, the products were obtained
in good yield when the reactants were treated with a stronger base sodium
hydride to form anions, which acted as nucleophilic attacker (Scheme 1).
In the chlorocarbonylation reaction, the by-product was N,N0-dialkoxycar-
bonyl-N,N0-diarylcarbamide (3), which can be detected by gas chromatography/
mass selective detector system (GC/MS). Besides, there were usually a little of
unchanged substrate N-arylcarbamate (1). The percentage of the by-product and
unchanged reactant were controlled by the reaction condition, especially the
amount of sodium hydride and triphosgene (Table 1). When the theoretic
amount of sodium hydride and triphosgene was used, the results were unsatisfac-
tory and the conversion of 1 was low (Entry 1). It suggests to us that the amount
of triphosgene was insufficient. However, by increasing the amount of triphos-
gene, the by-product was reduced a little, but the conversion was as low as before
(Entry 2.) By increasing the amount of sodium hydride, a higher conversion was
achieved, but the by-product increased much more than the product (2) (Entries
3 and 4). It reveals that the excessive amount of sodium hydride is important for
the completion of the reaction; because the anion formed by 1 and sodium
hydride cannot be dissolved in the solution, it prevents the interior sodium
hydride from reacting with 1. The formation of the by-product 3 is due to
reaction of the substrate (1) with the product (2) in the presence of a strong
Scheme 1.

N-Alkoxycarbonyl-N-arylamide
2663
Table 1. Effect of the reaction conditions
Composition of crude
product (%)a
3n(BTC)/ n(NaH)/
n(1)
Yield
(%)
Entry Substrate
n(1)
1
2
3
Purityb
1
2
1a
1a
1a
1a
1a
1a
1b
1b
1b
1c
1d
1
3
3
2
3
6
3
4
6
3
3
1
1
2
3
3
3
3
4
6
3
3
61
60
22
5
31
35
49
79
95
96
76
86
85
91
95
8
—
—
—
60
90
91
45
81
79
85
90
—
—
—
86
96
97
87
89
88
95
98
5
29
16
5
3
4
5
0
6
0
4
7
6
18
10
13
7
8
4
9
2
10
11
2
3
2
aGC assays of the reaction mixture treated by ice water.
bGC purity of isolated product.
base, sodium hydride, so the excessive triphosgene should be used to inhibit the
side reaction. When the amount of sodium hydride and triphosgene both
increased, the percentage of the product observably increased and the by-
product and unchanged reactant increased a little (Entries 5, 6, 9–11). Further
increase of triphosgene shows little contribution to the result (Entries 5 and 6).
EXPERIMENTAL
1H NMR spectra were measured on a Varian VA 400-MHz spectrometer with
TMS as an internal standard. Melting points were determined using a Yanaco
MP-500 apparatus and are uncorrected. HRMS were performed on Micromass
EI-TOF-MS instrument. GC were run on HP6890 gas chromatography. GC/
MS were performed on HP6890GC/5973MSD gas chromatography/mass
selective detector system.
General Method for the Synthesis of N-Chloroformyl-N-
arylcarbamate
In a first reaction flask, 0.013 mol of N-arylcarbamate (1) was dissolved in
20 mL of toluene. Then 52% sodium hydride in mineral oil was added
followed by 8 mL of glyme (ethylene glycol dimethyl ether) within 15 min.
The reaction mixture was stirred overnight (ca. 16 h) without external

2664
Y. Zhou, R. Gong, and W. Miao
heating. In a second reaction flask, triphosgene was dissolved in 10 mL of
toluene, which was cooled to 0–5 8C. The reaction mixture from the first
flask, a thick slurry, was slowly added to the second flask containing the tri-
phosgene solution at 0–5 8C. After addition was complete, the mixture was
stirred for additional 0.5 h at the same temperature. Then the reaction
mixture is cooled to about 8C, and 20 mL of ice water was added to the
reaction mixture with vigorous stirring. The toluene layer is separated from
the aqueous layer, washed twice with 20 mL of ice water, and dried with
MgSO4. The dried toluene solution was then distilled in vacuum to take off
the toluene. When the toluene was removed, 2 mL of hexane was added.
The hexane solution is then cooled to 0–5 8C, whereupon the product was pre-
cipitated, recovered by filtration, washed with additional cold hexane, and
dried to obtained a white crystal as product.
Data
Methyl N-chloroformyl-N-phenylcarbamate (2a), mp 127–128 8C (lit.[6]
1
128 8C); H NMR (400 MHz, CDCl3), d: 7.4–7.5(m, 3H), 7.2–7.3 (m, 2H),
3.81 (s, 3H); HRMS, m/z: 213.0194 (Mþ, calcd. 213.0193), 178.0543 ([M-
Cl]þ), 134.0608 ([M-Cl-CO2]þ), 119.0353 (base, [M-ClCOOCH3]þ).
Methyl N-chloroformyl-N-(4-trifluoromethoxy)phenylcarbamate (2b), mp
1
96–98 8C (lit.[3] 97–99 8C); H NMR (400 MHz, CDCl3), d: 7.30 (s, 4H),
3.80 (s, 3H); HRMS, m/z: 297.0017 (Mþ, calcd. 297.0015), 253.0118 ([M-
CO2]þ), 218.0430 ([M-Cl-CO2]þ), 203.0195 (base, [M-ClCOOCH3]þ).
Methyl N-chloroformyl-N-(4-trifluoromethyl)phenylcarbamate (2c), mp 109–
111 8C; 1H NMR (400 MHz,CDCl3), d: 7.74 (d, 2H, J ¼ 8.0 Hz), 7.41 (d, 2H,
J ¼ 8.0 Hz), 3.84 (s, 3H); HRMS, m/z: 281.0066 (Mþ, calcd. 281.0066),
246.0381 ([M-Cl]þ), 237.0170 ([M-CO2]þ), 202.0481 ([M-Cl-CO2]þ),
187.0236 (base, [M-ClCOOCH3]þ).
Ethyl N-chloroformyl-N-(4-trifluoromethyl)phenylcarbamate (2d), mp 94–
95 8C; 1H NMR (400 MHz,CDCl3), d: 7.73 (d, 2H, J ¼ 8.0 Hz), 7.40 (d, 2H,
J ¼ 8.0 Hz), 4.30 (q, 2H, J ¼ 7.2 Hz); 1.26 (t, 3H, J ¼ 7.2 Hz); HRMS, m/z:
295.0225 (Mþ, calcd. 295.0223), 223.0013 ([M-HCOOCHCH2]þ), 188.0325
([M-HCOOCHCH2-Cl]þ), 187.0237 (base, [M-HCOOCHCH2-HCl]þ).
EIMS Data of 3a–3d
N,N0-Dimethoxycarbonyl-N,N0-diphenylcarbamide (3a), m/z: 328 (Mþ), 209
([M-PhNCO]þ), 178 ([M-PhNCO-OCH3]þ), 150 ([M-PhNCO-OCH3-
CO]þ), 134 ([M-PhNCO-OCH3-CO2]þ), 119 (base, [PhNCO]þ).

N-Alkoxycarbonyl-N-arylamide
2665
N,N0-Dimethoxycarbonyl-N,N0-di(4-trifluoromethoxy)phenylcarbamide (3b),
m/z: 293 ([M-CF3OPhNCO]þ), 262 ([M-CF3OPhNCO-OCH3]þ), 234 ([M-
CF3OPhNCO-OCH3-CO]þ), 218 ([M-CF3OPhNCO-OCH3-CO2]þ), 203
(base, [CF3OPhNCO]þ).
N,N0-Dimethoxycarbonyl-N,N0-di(4-trifluoromethoxyl)phenylcarbamide (3c),
m/z: 277 ([M-CF3PhNCO]þ), 246 ([M-CF3PhNCO-OCH3]þ), 218 ([M-
CF3PhNCO-OCH3-CO]þ), 202 (base, [M-CF3PhNCO-OCH3-CO2]þ), 187
([CF3PhNCO]þ).
N,N0-Dimethoxycarbonyl-N,N0-di(4-trifluoromethoxy)phenylcarbamide (3d),
m/z: 305 ([M-CF3PhNCO]þ), 260 ([M-CF3PhNCO-OC2H5]þ), 232 ([M-
CF3PhNCO-OC2H5-CO]þ), 216 (base, [M-CF3PhNCO-OC2H5-CO2]þ), 187
([CF3PhNCO]þ).
ACKNOWLEDGMENTS
This study was supported by the Doctor Foundation of Liaoning Province,
China (No. 20031068).
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