Preparative synthesis of cyclohexanone oxime esters

Article abstract of DOI:10.1134/S1070428008090248

Preparative procedures have been developed for the synthesis of cyclohexanone oxime esters by acylation of cyclohexanone oxime with carboxylic acid anhydrides in the presence of perchloric acid or with carboxylic acid chlorides in the presence of pyridine

Full text of DOI:10.1134/S1070428008090248

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 9, pp. 1389–1391. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © E.A. Dikusar, N.A. Zhukovskaya, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 9, pp. 1406–1408.
Preparative Synthesis of Cyclohexanone Oxime Esters
E. A. Dikusar and N. A. Zhukovskaya
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus,
ul. Surganova 13, Minsk, 220072 Belarus
e-mail: evgen_58@mail.ru
Received November 20, 2007
Abstract—Preparative procedures have been developed for the synthesis of cyclohexanone oxime esters by
acylation of cyclohexanone oxime with carboxylic acid anhydrides in the presence of perchloric acid or with
carboxylic acid chlorides in the presence of pyridine.
DOI: 10.1134/S1070428008090248
We previously reported on the synthesis of men-
thone oxime esters that attract interest as grassy and
fruity aromatizers for perfumery and food industry [1].
The goal of the present work was to develop prepara-
tive procedures for the synthesis of cyclohexanone
oxime esters. Cyclohexanone oxime (I) is an acces-
sible and relatively inexpensive reagent which is
widely used in industry for separation and concentra-
tion of chemical elements [2]. We anticipated that
esters derived from cyclohexanone oxime (I) could
possess a pleasant odor. Comparison of the odors of
esters derived from cyclohexanone and menthone
(2-isopropyl-5-methylcyclohexanone) oximes [1]
should make it possible to estimate the contribution of
substituents in the cyclohexane ring to variation of
their odor.
longed stirring was necessary. The corresponding
cyclohexanone oxime esters IIIa–IIIs were isolated in
87–92% yield.
Compounds IIIa–IIIs are colorless liquids or crys-
talline substances. They were isolated sufficiently pure
(they contained no impurities of initial compounds,
hexane, or pyridine), so that they can be used directly
in perfume and food industry [3]. According to the
1H NMR data, the purity of oxime esters IIIa–IIIs was
97–98%. Compounds IIIa–IIIs can be stored for
a long time at a temperature below 5°C with protection
from light and atmospheric oxygen.
The IR, UV, and 1H NMR spectra of cyclohexanone
oxime esters IIIa–IIIs were consistent with their struc-
ture. The IR spectra of IIIa–IIIs contained absorption
bands in the regions 3000–2800 (C–Haliph), 1765–1740
(C=O), 1642–1638 (C=N), 1470–1450 (CH2), and
1200–1050 cm–1 (C–O); esters IIIn–IIIq derived from
aromatic carboxylic acids displayed in the IR spectra
Cyclohexanone oxime esters were synthesized by
reaction of cyclohexanone oxime (I) with aliphatic
carboxylic acid anhydrides IIa–IId in hexane in the
presence of a catalytic amount of 57% HClO4 or with
aliphatic and aromatic acid chlorides IIe–IIs in hexane
in the presence of pyridine (Scheme 1). The reactions
were carried out by mixing equimolar amounts of the
reactants, followed by keeping the mixture for 24–48 h
at 20–23°C. Neither strong external cooling nor pro-
absorption bands at 3100–3000 and 900–680 (C–Harom
)
and 1600–1320 cm–1 (C–Carom); in the IR spectrum of
IIIq the C=C stretching vibration band was located at
1631 cm–1. The electronic spectra of cyclohexanone
oxime esters IIIa–IIIm, IIIr, and IIIs showed an ab-
sorption maximum at λ 208 nm (ε = 8000); compound
Scheme 1.
(RCO)2O (IIa–IId), HClO4 or
RCOCl (IIe–IIs), pyridine
NOH
NOCOR
I
IIIa–IIIs
R = Me (a), Et (b), Pr (c), i-Pr (d), Bu (e), i-Bu (f), Me(CH2)4 (g), Me(CH2)5 (h), Me(CH2)6 (i), Me(CH2)7 (j), Me(CH2)8 (k),
Me(CH2)11 (l), cyclo-C6H11 (m), Ph (n), Ph(CH2)2 (o), PhCH(Me)CH2 (p), trans-PhCH=CH (q), MeO (r), EtO (s).
1389

DIKUSAR, ZHUKOVSKAYA
1390
IIIn was characterized by absorption maxima at λ 208
(ε = 23 000), 225 (ε = 14 000), and 260 nm (ε =
12000); oximes esters IIIo and IIIp showed a maxi-
mum at λ 209 nm (ε = 15000); absorption maxima of
IIIs were observed at λ 208 (ε = 30 000), 223 (ε =
23000), 274 (ε = 20000), and 290 nm (ε = 4000).
Cyclohexanone O-acetyloxime (IIIa). Yield 87%,
20
d = 0.9870, nD20 = 1.4835. Found, %: C 62.24; H 8.51;
20
N 8.76. M 144.7. C8H13NO2. Calculated, %: C 61.91;
H 8.44; N 9.03. M 155.2.
Cyclohexanone O-propanoyloxime (IIIb). Yield
88%, d2200 = 0.9856, nD20 = 1.4825. Found, %: C 64.07;
H 9.10; N 8.09. M 157.9. C9H15NO2. Calculated, %:
C 63.88; H 8.93; N 8.28. M 169.2.
1
In the H NMR spectra of IIIa–IIIs protons in the
cyclohexane ring resonated in the region δ 1.55–
2.85 ppm; protons of the acetyl group in IIIa gave
a singlet at δ 2.12 ppm; signal from the methoxy group
of methyl carbonate IIIr was located at δ 3.85 ppm (s);
signals from the EtCOO and EtO groups of IIIb and
IIIs appeared as triplets at δ 1.15–1.23 ppm (Me) and
quartets at δ 2.30–2.42 ppm (CH2); the Me2C group in
IIIe gave a doublet at δ 1.22 ppm; and aromatic pro-
tons in compounds IIIn–IIIq resonated in the region
δ 7.00–8.30 ppm.
Cyclohexanone O-butanoyloxime (IIIc). Yield
20
89%, d = 0.9833, nD20 = 1.4800. Found, %: C 65.83;
20
H 9.52; N 7.41. M 171.3. C10H17NO2. Calculated, %:
C 65.54; H 9.35; N 7.64. M 183.2.
Cyclohexanone O-(2-methylpropanoyl)oxime
20
(IIId). Yield 88%, d = 0.9521, nD20 = 1.4775. Found,
20
%: C 65.72; H 9.39; N 7.35. M 176.4. C10H17NO2. Cal-
culated, %: C 65.54; H 9.35; N 7.64. M 183.2.
b. Anhydrous pyridine, 0.01 mol, was added to
a solution of 0.01 mol of cyclohexanone oxime (I) in
50 ml of hexane, the mixture was cooled to 15°C, and
0.01 mol of carboxylic acid chloride IIe–IIs was added
under careful shaking. The mixture was left to stand
for 24–36 h at 20–23°C, diluted with water, and ex-
tracted with hexane. The organic phase was separated,
washed with water and a 5% solution of sodium hydro-
gen carbonate, and dried over CaCl2. The solvent was
removed under reduced pressure (30–45 mm) at a tem-
perature not exceeding 25–30°C.
Organoleptic evaluation of cyclohexanone oxime
(I) and its esters IIIa–IIIs was performed by the
Degustation Council at the Tereza-Inter Ltd. Control
Analytical Laboratory (Moscow). No odor was re-
vealed for pure samples of cyclohexanone oxime (I)
and its O-acyl derivatives IIIa–IIIs.
EXPERIMENTAL
The IR spectra were recorded from films (neat) or
KBr pellets on a Nicolet Protege-460 spectrometer.
The UV spectra were measured from 1×10–3 M solu-
tions in methanol on a Specord UV-Vis spectro-
Cyclohexanone O-pentanoyloxime (IIIe). Yield
20
91%, d = 0.9688, nD20 = 1.4745. Found, %: C 67.20;
20
1
H 9.86; N 6.90. M 190.0. C11H19NO2. Calculated, %:
C 66.97; H 9.71; N 7.10. M 197.3.
photometer. The H NMR spectra were obtained from
5% solutions in chloroform-d on a Tesla BS-587A
instrument at 100 MHz; the chemical shifts were
determined relative to tetramethylsilane as internal
reference. The molecular weights were determined by
cryoscopy in benzene.
Cyclohexanone O-(3-methylbutanoyl)oxime
20
(IIIf). Yield 89%, d = 0.9389, nD20 = 1.4765. Found,
20
%: C 67.14; H 9.84; N 6.85. M 188.3. C11H19NO2. Cal-
culated, %: C 66.97; H 9.71; N 7.10. M 197.3.
Cyclohexanone O-hexanoyloxime (IIIg). Yield
Commercial cyclohexanone oxime (I) with a purity
of 97% was used, mp 89–91°C.
20
89%, d = 0.9556, nD20 = 1.4765. Found, %: C 68.36;
20
H 10.15; N 6.42. M 204.5. C12H21NO2. Calculated, %:
C 68.21; H 10.02; N 6.63. M 211.3.
Cyclohexanone oxime esters IIIa–IIIs (general
procedure). a. Cyclohexanone oxime (I), 0.01 mol, and
carboxylic acid anhydride IIa–IId, 0.011 mol, were
dissolved in 30 ml of hexane, one drop of 57% per-
chloric acid was added, and the mixture was stirred by
shaking and was left to stand for 24–36 h at 20–23°C.
The mixture was then diluted with water and extracted
with hexane, the organic phase was separated, washed
with water and a 5% solution of sodium hydrogen
carbonate, and dried over CaCl2, and the solvent was
removed under reduced pressure (30–45 mm) at a tem-
perature not exceeding 25–30°C.
Cyclohexanone O-heptanoyloxime (IIIh). Yield
20
87%, d = 0.9213, nD20 = 1.4765. Found, %: C 69.55;
20
H 10.31; N 5.97. M 214.8. C13H23NO2. Calculated, %:
C 69.30; H 10.29; N 6.22. M 225.3.
Cyclohexanone O-octanoyloxime (IIIi). Yield
20
90%, d = 0.9599, nD20 = 1.4770. Found, %: C 70.43;
20
H 10.65; N 5.70. M 222.8. C14H25NO2. Calculated, %:
C 70.25; H 10.53; N 5.85. M 239.4.
Cyclohexanone O-nonanoyloxime (IIIj). Yield
20
92%, d = 1.0158, nD20 = 1.4750. Found, %: C 71.38;
20
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 9 2008

PREPARATIVE SYNTHESIS OF CYCLOHEXANONE OXIME ESTERS
1391
H 10.96; N 5.22. M 239.0. C15H27NO2. Calculated, %:
C 71.10; H 10.74; N 5.53. M 253.4.
%: C 74.45; H 8.24; N 5.08. M 241.8. C16H21NO2. Cal-
culated, %: C 74.10; H 8.16; N 5.40. M 259.3.
Cyclohexanone O-decanoyloxime (IIIk). Yield
89%, mp 24–25°C. Found, %: C 72.03; H 11.05;
N 5.02. M 258.4. C16H29NO2. Calculated, %: C 71.87;
H 10.93; N 5.24. M 267.4.
Cyclohexanone O-[(E)-3-phenylprop-2-enoyl)-
oxime (IIIq). Yield 90%, mp 85–86°C. Found, %:
C 74.37; H 7.22; N 5.58. M 231.7. C15H17NO2. Cal-
culated, %: C 74.05; H 7.04; N 5.76. M 243.3.
Cyclohexanone O-tridecanoyloxime (IIIl). Yield
90%, mp 35–36°C. Found, %: C 73.91; H 11.45;
N 4.23. M 295.6. C19H35NO2. Calculated, %: C 73.74;
H 11.40; N 4.53. M 309.5.
Cyclohexanone O-(methoxycarbonyl)oxime
(IIIr). Yield 88%, mp 27–28°C. Found, %: C 56.36;
H 7.71; N 7.89. M 160.1. C8H13NO3. Calculated, %:
C 56.13; H 7.66; N 8.18. M 171.2.
Cyclohexanone O-(cyclohexylcarbonyl)oxime
Cyclohexanone O-(ethoxycarbonyl)oxime (IIIs).
20
(IIIm). Yield 88%, d = 1.0708, nD20 = 1.5050. Found,
20
Yield 87%, d = 1.1160, nD20 = 1.4735. Found, %:
20
20
%: C 70.18; H 9.56; N 6.04. M 217.7. C13H21NO2. Cal-
culated, %: C 69.92; H 9.48; N 6.27. M 223.3.
C 58.54; H 8.39; N 7.31. M 179.4. C9H15NO3. Cal-
culated, %: C 58.36; H 8.16; N 7.56. M 185.2.
Cyclohexanone O-benzoyloxime (IIIn). Yield
87%, mp 56–57°C. Found, %: C 72.12; H 7.08; N 6.12.
M 208.4. C13H15NO2. Calculated, %: C 71.87; H 6.96;
N 6.45. M 217.3.
REFERENCES
1. Zhukovskaya, N.A., Dikusar, E.A., Moiseichuk, K.L.,
and Vyglazov, O.G., Zh. Prikl. Khim., 2006, vol. 79,
p. 642.
Cyclohexanone O-(3-phenylpropanoyl)oxime
20
(IIIo). Yield 88%, d = 1.1226, nD20 = 1.5410. Found,
20
2. Peshkova, V.M., Savostina, V.M., and Ivanova, E.K.,
%: C 73.69; H 7.96; N 5.45. M 229.6. C15H19NO2. Cal-
culated, %: C 73.44; H 7.81; N 5.71. M 245.3.
Oksimy (Oximes), Moscow: Nauka, 1977, p. 238.
3. Sarafanova, L.A. Pishchevye dobavki: entsiklopediya
(Food Additives: Encyclopedia), St. Petersburg: GIRD,
2003, p. 688.
Cyclohexanone O-(3-phenylbutanoyl)oxime
20
(IIIp). Yield 91%, d = 1.1609, nD20 = 1.5345. Found,
20
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 9 2008