Synthesis and structure-aroma correlation of citral oxime esters

Full text of DOI:10.1007/s10600-008-0022-z

Chemistry of Natural Compounds, Vol. 44, No. 1, 2008
SYNTHESIS AND STRUCTURE—AROMA CORRELATION
OF CITRAL OXIME ESTERS
E. A. Dikusar,1 N. A. Zhukovskaya,1 K. L. Moiseichuk,1
E. G. Zalesskaya,1 O. G. Vyglazov,2 and P. V. Kurman1
UDC 547.92+547.574.2+
547.362+547.288.4
Citral (3,7-dimethyl-2,6-octadienal, 1) occurs in lemongrass, cubeb, citrus, and other essential oils as a mixture of the
- and -isomers in a 7:3 ratio. This aldehyde (1) has a strong lemon odor [1] and is used widely in many perfume
E
Z
compositions.
The goal of our work was to develop preparative synthetic methods of citral oxime esters through the reaction of citral
oxime (2) with alkylcarboxylic acid anhydrides or alkyl- and arylcarboxylic acid chlorides in the presence of pyridine. The
synthesis was performed at 20-23°C for 24-36 h bysimplymixing the appropriate reagents and proceeded without using cooling
and prolonged stirring. Citral oxime esters 3-22 were prepared in 74-88% yield.
Me C CH(CH ) C(Me) CHCH
O
Me C CH(CH ) C(Me) CHCH NOH
2 2
2
2 2
2
1
2
Me C CH(CH ) C(Me) CHCH NOC(O)R
2 2
2
3 - 22
R = Me (3), Et (4), Pr (5), CHMe2 (6), CH2CHMe2 (7), (CH2)4Me (8), (CH2)5Me (9),
(CH2)6Me (10), (CH2)7Me (11), (CH2)11Me (12), (CH2)16Me (13), C6H11-cyclo (14),
C6H5 (15), (CH2)2C6H5 (16), CH=CHC6H5-cis (17), C(C N)=CHC6H5 (18),
C6H4NO2-3 (19), OMe (20), OEt (21), (CH2)2C(O)OMe (22)
Esters 3-22 are colorless or slightly colored liquids (3-17 and 19-22) or a crystalline compound (18, crystallized from
hexane). The esters did not need further purification; contained no impurities of starting materials, benzene, and pyridine; and
were suitable for direct use in the perfumery and food industries. The products were 96-98% pure according to PMR
spectroscopy. Esters 3-22 are very stable at temperatures below +5°C if protected from air and light. They were stabilized
against polymerization by adding hydroquinone (0.5%).
The structures and compositions of esters 3-22 were confirmed by elemental analysis, cryoscopic determination of
molecular weights, PMR spectra, and IR spectra. The analytical results and determined molecular weights of all synthesized
compounds agreed with those calculated.
IR spectra of 3-22 contained absorption bands in the range 3000-2800 cm−1 for (CH ), 3050-3020 (=CH), 1770-1740
Alk
(C=O), 1670-1665 (C=C), 1645-1635 (C=N), 1667-1663 (CH ), and 1250-1180 (C–O). IR spectra of esters of aromatic
2
carboxylic acids (15-19) had absorption bands for (CH ) in the range 3100-3000 and 707-690 cm−1; 1600-1595, 1455-1450,
Ar
1370-1370, and 1315-1313 (Ar). The IR spectrum of 18 had an absorption band for (C≡N) at 2219 cm−1. The NO band for
2
19 appeared as two characteristic absorption bands at 1535 and 1350 cm−1. IR spectra of the compounds as thin layers or KBr
disks were recorded on a Nicolet Protege-460 IR Fourier spectrophotometer.
1) Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, 220072, Minsk, ul. Surganova,
13, e-mail:evgen_58@mail.ru;2) OOOTereza Inter,Russia,129110, Moscow, Olimpiiskii pr., 22, e-mail: ilb_chuiko@mail.ru.
Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 65-66, January-February, 2008. Original article submitted
November 21, 2007.
0009-3130/08/4401-0081 ©2008 Springer Science+Business Media, Inc.
81

TABLE 1. Aroma of Citral Oxime (2) and Citral Oxime Esters 3 - 17 and 20 - 22
No.
Aroma
2
3
4
Citrus-woody with a trace of dry fruit
Sweet lemon with a hint of grapefruit
Sweet lemon with a hint of anise and ripe apple
Citrus with a hint of viburnum
5
6
7
8
Citrus with a hint of apricot peel
Citrus-herbaceous with a hint of pineapple
Citrus with a hint of plum peel
9
Citrus with a hint of wood bark
10
11
12
13
14
15
16
17
20
21
22
Citrus and ozone with a hint of resin
Citrus and plum with a hint of tarrragon
Citrus and oily with a hint of pear
Citrus and bitter with a hint of berry
Citrus with a trace of sharp apple
Lemon and cologne with a hint of ozone
Lemon with a hint of medicinal herbs
Lemon with a hint of coriander
Lime with a hint of cranberry
Lime with a hint of bilberry
Lime with a hint of wormwood
PMR spectra of 3-22 showed resonances for the moiety (Me C=C) as two broad singlets at 1.60 ± 0.05 and 1.66 ±
2
0.04 ppm; (MeC=C), a broad singlet at 2.05 ± 0.05; and (HC=C), resonances at 4.90-6.40. Resonances of aromatic protons of
esters 15-19 appeared as a multiplet at 7.10-9.00 ppm. PMR spectra of 3-22 contained characteristic resonances corresponding
to the ester group [2]. PMR spectra in CDCl (5% solutions) were obtained on a BS-587A spectrometer (100 MHz, Tesla).
3
Chemical shifts were determined relative to TMS internal standard.
The Tasting Council of accredited monitoring-analytical laboratory OOO Tereza-Inter (Moscow) evaluated the
organoleptic aromas of the synthesized citral oxime esters 3-17 and 20-22. Table 1 lists the statistical average data for the pure
products. Practicallyall prepared esters have some citrus aroma with different traces of fruit, berry, or spice. This enables them
to be used as imitation food flavors and fruit and berry fragrances. Ester 15 is interesting because it has a clear fresh ozone and
cologne aroma, which makes it promising for use in perfumery.
Citral oxime (2) was synthesized by the literature method [3]. Its physical chemical properties agreed with those
published [4].
Citral Oxime Esters 3-6. Citral oxime (2, 0.01 mol) and the appropriate acid anhydride (0.011 mol) were mixed,
shaken, left at 20-23°C for 24-36 h, and diluted with water. The product was extracted with hexane. The organic layer was
separated, washed with water and NaHCO solution (5%), and dried over CaCl . Solvent was removed at reduced pressure
3
2
(p = 10-15 mm Hg), keeping the temperature below 25-30°C. The product was dried in vacuo (p = 2·10−2 mm Hg). Esters 3-6
were purified finallybypreparative column chromatographyover Al O (Brockman activityII, neutral) with elution bybenzene
2
3
with hexane. The molecular weights were determined by cryoscopy in benzene.
The following compounds were prepared by this method.
N-Acetyloxyimino-3,7-dimethyl-2,6-octadiene (3). Yield 86%, d
N-Propionyloxyimino-3,7-dimethyl-2,6-octadiene (4). Yield 90%, d
N-Butyryloxyimino-3,7-dimethyl-2,6-octadiene (5). Yield 83%, d
20
20
1.0589, n
1.4968, C H NO .
12 19 2
20
D
20
20
0.9758, n
1.4920, C H NO .
13 21 2
20
20
D
20
0.9859, n
1.4794, C H NO .
14 23 2
20
D
20
20
N-iso-Butyryloxyimino-3,7-dimethyl-2,6-octadiene (6). Yield 85%, d
1.0035, n
1.4750, C H NO .
14 23 2
20
D
Citral Oxime Esters 7-22. Citral oxime (2, 0.01 mol) was dissolved in absolute pyridine (0.011 mol), cooled to 15°C,
stirred, treated carefully with the appropriate acid chloride (0.011 mol), left at 20-23°C for 24-36 h, and diluted with water.
The product was extracted with hexane (7-14, 20-22) or benzene (15-19). The organic layer was separated, washed with water
and NaHCO solution (5%), and dried over CaCl . Solvent was removed at reduced pressure (p = 10-15 mm Hg), keeping the
3
2
temperature below 25-30°C. The product was dried in vacuo (p = 2·10−2 mm Hg). Esters 7-22 were finally purified by
preparative column chromatography over Al O (Brockman activity II, neutral) with elution by benzene with hexane.
2
3
82

The following compounds were prepared by this method.
N-iso-Valeroyloxyimino-3,7-dimethyl-2,6-octadiene (7). Yield 92%, d
N-Caproyloxyimino-3,7-dimethyl-2,6-octadiene (8). Yield 88%, d
N-Enanthoyloxyimino-3,7-dimethyl-2,6-octadiene (9). Yield 93%, d
N-Caprylyloxyimino-3,7-dimethyl-2,6-octadiene (10). Yield 84%, d
N-Pelargonyloxyimino-3,7-dimethyl-2,6-octadiene (11). Yield 85%, d
N-Tridecanoyloxyimino-3,7-dimethyl-2,6-octadiene (12). Yield 86%, d
N-Stearyloxyimino-3,7-dimethyl-2,6-octadiene (13). Yield 85%, d
20
20
0.9785, n
1.4876, C H NO .
15 25 2
20
D
20
20
0.8114, n
1.4798, C H NO .
16 27 2
20
D
20
20
0.8901, n
0.9974, n
1.4808, C H NO .
17 29 2
20
20
D
20
1.4839, C H NO .
18 31 2
20
20
D
20
0.9785, n
1.4842, C H NO .
19 33 2
20
D
20
20
0.9130, n
1.4798, C H NO .
20
D
23 41
2
20
20
1.0580, n
1.4798, C H NO .
28 51 2
20
D
20
20
N-Cyclohexanecarboxyloxyimino-3,7-dimethyl-2,6-octadiene (14). Yield 80%, d
1.0501, n
1.5025,
20
D
C H NO .
17 27
2
20
20
N-Benzoyloxyimino-3,7-dimethyl-2,6-octadiene (15). Yield 84%, d
1.0224, n
1.5208, C H NO .
17 21 2
20
D
20
20
N-(3-Phenylpropionyloxyimino)-3,7-dimethyl-2,6-octadiene (16). Yield 87%, d
0.9530, n
1.5268,
20
D
C H NO .
19 25
2
20
20
N-trans-Cinnamyloxyimino-3,7-dimethyl-2,6-octadiene (17). Yield 81%, d
1.0752, n
1.5724, C H NO .
19 23 2
20
D
N-trans-2-Cyanocinnamyloxyimino-3,7-dimethyl-2,6-octadiene (18). Yield 80%, mp 38-39 C, C H N O .
20 22
1.5424, C H N O .
17 22 2 4
2 2
20
20
N-3-Nitrobenzoyloxyimino-3,7-diemthyl-2,6-octadiene (19). Yield 83%, d
1.1376, n
20
20
D
20
N-3,7-Dimethyl-2,6-octadieniminomethylcarbonate (20). Yield 82%, d
0.9310, n
0.9836, n
0.8945, n
1.4856, C H NO .
12 19 3
1.4860, C H NO .
13 21 3
1.4848, C H NO .
15 23 4
20
20
D
20
N-3,7-Dimethyl-2,6-octadieniminoethylcarbonate (21). Yield 84%, d
20
D
20
20
N-3,7-Dimethyl-2,6-octadieniminomethylsuccinate (22). Yield 86%, d
20
D
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