A convenient procedure for the preparation of oxime chloroformates

Article abstract of DOI:10.1081/SCC-120023999

Triphosgene is a convenient reagent for the preparation of O-(chloroformyl)oximes from aliphatic and aromatic ketoximes.

Full text of DOI:10.1081/SCC-120023999

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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 19, pp. 3405–3410, 2003
A Convenient Procedure for the Preparation
of Oxime Chloroformates
*
Z. Paryzek and H. Koenig
Faculty of Chemistry, A. Mickiewicz University,
Poznan, Poland
ABSTRACT
Triphosgene is a convenient reagent for the preparation of
O-(chloroformyl)oximes from aliphatic and aromatic ketoximes.
O-(Chloroformyl)oximes (2) are prepared from oximes (1) upon the
reaction with excess of phosgene in the yield ranging from 51 to 88%,
according to the original procedure of Jumar et al.[1] These ketone deri-
vatives are excellent substrates for the preparation of nitrilium salts[2]
under the Beckmann rearrangement conditions, while the reaction is
accompanied by the evolution of carbon dioxide. Ketoxime chlorofor-
mates react easily with alcohols, amines, thiols, and hydroperoxides to
*Correspondence: Z. Paryzek, Faculty of Chemistry, A. Mickiewicz University,
Grunwaldzka 6, 60-780 Poznan, Poland; Fax: +48 61 8291324; E-mail:
zparyzek@amu.edu.pl.
3405
DOI: 10.1081/SCC-120023999
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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3406
Paryzek and Koenig
give the respective derivatives.[1,3] The efficientBeckmann rearrangement
of ethyl carbonates (4, X ¼ O, R ¼ Et) has recently been reported.[4]
In synthesis, the highly toxic gaseous phosgene (5) has been success-
fully replaced by liquid trichloromethyl chloroformate (diphosgene 6) or
R
R
OH
_
+
N
C
N
R
C
R
SbCl6
3
1
COCl2
solvent
SbCl5 / CH2Cl2
O
O
R
O C XR
R
O C Cl
RXH
C
N
C
N
R
R
2
4
(X = O, OO, S, NH)
solid bis(trichloromethyl)carbonate (triphosgene 7) as safer and more con-
venient phosgene substitutes. These reactions include chloroformylation,
carbonylation, chlorination, and dehydration.[5] In other examples
triphosgene is used for preparation of carbonates,[6] lactams,[7] and
COCl2
5
Cl-CO2CCl3 Cl3C-OCO-CCl3
6
7
R
O
CO OCCl3
O
CO OEt
C
N
C
N
R
8
9
chloro compounds.[8] The application of diphosgene and triphosgene
for the preparation of O(chloroformyl)oximes has been questioned,
however.[2] The reaction of aliphatic and aromatic ketoximes with 2
and 3 was reported to give unseparable mixtures of chloroformyl esters
2 and (trichloromethoxy)formyl esters 8 in variable ratios. These mixtures
were reported as not suitable for further transformations to nitrilium
salts.[2] Since we required oxime derivatives of formula 2, the application
of triphosgene 7 as the source of phosgene was reconsidered.
We found that addition of 7 to the benzene-pyridine mixture at
À15ꢀC results in formation of yellow, solid complex of phosgene-pyridine

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Preparation of Oxime Chloroformates
3407
COCl2 2Py.[9] This in situ formed complex was then used for the prepara-
tion of chloroformates 2a–2f. This was accomplished by addition of the
solution of an oxime (0.33 mol equiv.) in benzene followed by reaction
carried out at room temperature for one to 2 h. The pure products
were isolated by filtration–evaporation–chromatography or extraction–
chromatography procedure in the yield exceeding 60%. When 10%
excess of 7 was used in the reaction with cyclohexanone oxime 1e, t he
yield of 2e did notimprove significanlty. The crude chloroformaets
were obtained in the yield 60–80% and their purity, as estimated by
1H NMR spectra, was sufficient for using them in further reactions.
Chromatography of crude chloroformates gave pure samples in the
yield generally over 65%. The formation of any traces of O-(trichloro-
methoxy)formyl esters (8) was excluded by careful analysis of 13C NMR
spectra of the reaction products, which did not show up signals at d 107.8
characteristic for trichloromethyl carbon atom –OCCl3. Finally, oxime
chloroformates could be transformed to the respective carbonates.
For example, compound 2e when treated with silver nitrite in ethanolic
solution gave the ketoxime ethylcarbonate 9.
.
EXPERIMENTAL
Melting point values were determined on a Kofler hot-stage apparatus
and are uncorrected. Infrared Spectra were determinated with a FT-IR
1
Bruker FS 113 V spectrophotometer for solutions in chloroform. H and
13C NMR spectra were recorded with a Varian Gemini 300 VT
spectrometer operating in the Fourier transform mode using solutions in
deuteriochloroform. The chemical shifts (d) are expressed in ppm relative
to tetramethylsilane. Electron impact mass spectra were recorded with a
AMD 402 spectrometer using ionization energy of 70 eV. The progress
of reactions and purity of compounds was monitored by TLC using a
precoated aluminium-backed silica plates (E. Merck, no. 5554). Silica gel
60 (Merck 70–230 mesh, no. 7734) was used for flash chromatography.
General Experimental Procedure for the Preparation of
Oxime Chloroformates
Triphosgene (7) (295 mg, 1 mmol) is added to the solution of pyridine
(0.8 mL, 10 mmol) in benzene (5 mL) at À15ꢀC. The solid yellow complex
is formed quickly. To this vigorously stirred mixture a solution of the
oxime (0.33 mmol) in benzene (2 mL) is added and the reaction mixture is

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3408
Paryzek and Koenig
warmed gradually to room temperature. Stirring is continued for 1 to 2 h,
while the solid turns white. The precipitate is filtered of, the precipitate is
washed with benzene and the filtrate is evaporated to give crude product.
This is chromatographed on silica gel column. Alternatively, the crude
product is isolated by dilution of the reaction mixture with benzene,
washing the benzene solution with water, drying (MgSO4), and evapora-
tion of the solvent under reduced pressure. The yields of chloroformates
2a–2f are given in the Table 1. The 1H and 13C NMR spectra of
chloroformates 2a–2c are in accordance with the published data.[2]
2d. Oil, ꢀmax: 1788 (C¼O), 1648 (C¼N); dH 2.44 and 2.38 (two q,
J ¼ 7.4 Hz, CH2CH3), 2.04 and 2.02 (two s ,CH3), 1.17 and 1.13 (two t ,
J ¼ 7.4 Hz, CH3); dC: isomer anti: 10.6, 14.8, 28.9, 152.7, 167.9; isomer
syn: 10.0, 19.2, 23.7, 159.6, 168.6; m/z: 87 (Mþ–COCl), 70 (Mþ–OCOCl).
2e. Oil, ꢀmax: 1796 (C¼O), 1643 (C¼N); dH 2.58 (2H, t, J ¼ 6.3 Hz),
2.40 (2H, t, J ¼ 6.3 Hz), 1.70 (6H, m); dC 168.7 (C¼O), 153.0 (C¼N),
31.9, 26.8, 25.8, 25.4 m/z: 96 (Mþ-OCOCl).
2f. M.p. 168–172ꢀC (from ethyl acetate); ꢀmax: 1783 (C¼O), 1641
(C¼N); dH 3.18 (1H, d, J ¼ 14.3 Hz), 2.95 (1H, d, J ¼ 14.4 Hz), 2.57
(1H, d, J ¼ 15.1 Hz), 2.4À2.0 (5H, m), 0.91 (3H, s, C-19), 0.659 (3H, s,
C-18); dC 168.8 (C¼O), 153.2 (C¼N); m/z: 401 (Mþ–COCl), 385
(Mþ–OCOCl), 246, 231.
Table 1. The preparation of the oxime chloroformates.
1
1
R
R
O CO Cl
R
R
OH
7, PhH/Py
C
N
C
N
- 15oC, 1-2 h
2
2
1a-1f
2a-2f
The yield of 2 after
chromatography
(crude product)
The isolation
procedurea
R1
R2
a
b
c
CH3
CH3
Ph
CH3
Ph
A
B
A
B
B
A
B
B
55
64
Ph
57 (79)
45 (78)
67
d
e
CH3
C2H5
(CH2)5
62
66 (77)
60 (73)
f
3-cholestane
aA: filtration-chromatography; B: extraction-chromatography.

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Preparation of Oxime Chloroformates
The Preparation of Oxime Ethylcarbonate 9
3409
To a solution of the chloroformate 2e (21.2 mg) in ethanol (0.6 mL) a
solution of silver nitrite (26.6 mg) in ethanol (1.6 mL) was added and the
mixture was refluxed for 0.5 h until all the substrate reacted (TLC test).
The solvent was evaporated and the residue was filtered through a short
column of silica gel to give pure 9 as an oil. dH: 4.31 (q, 2H, J ¼ 7.1,
CH2CH3), 2.56 (t, 2H, J ¼ 6.6 Hz), 2.37 (t, 2H, J ¼ 6.6 Hz), 1.69 (m, 6H),
1.36 (t, 3H, J ¼ 7.1 Hz, CH3). Anal. calcd. for C9H15NO3: C, 58.36; H,
8.16; N, 7.56. Found: C, 58.30; H, 8.50; N, 7.34.
ACKNOWLEDGMENTS
Financial support of the work by the State Committee for Scientific
Research (projectNo. 7 T09A 110 21) is graetfully acknowledged.
REFERENCES
¨
1. Jumar, A.; Held, P.; Schulze, W. Uber die Herstellung und
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¨
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2. Jochims, Johannes C.; Hehl, S.; Herzberger, S. Preparation and
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1990, 12, 1128–1133.
O-(chlorooxalyl)oximes. Synthesis
3. Ruchardt, Ch.; Pantke, R. Darstellung und Thermolyse von O-tert-
¨
Butylperoxycarbonylketoximen. Chem. Ber. 1971, 104, 3456–3462.
4. Anilkumar, R.; Chandrasekhar, S. Improved procedures for the
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3410
Paryzek and Koenig
8. Goren, Z.; Heeg, Mary J.; Mobashery, S. Facile chloride substitution
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Received in the USA March 21, 2003

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