Synthesis and structure - Aroma correlation of anisaldehyde oxime esters

Article abstract of DOI:10.1007/s10600-009-9264-7

Preparative syntheses from anisaldehyde 1 of the anti-isomer of anisaldehyde oxime 2 and anisaldehyde oxime esters 3a-q in 84-93% yields were developed. The structure - aroma correlation of 2 and 3a-q was studied.

Full text of DOI:10.1007/s10600-009-9264-7

Chemistry of Natural Compounds, Vol. 45, No. 2, 2009
SYNTHESIS AND STRUCTURE—AROMA CORRELATION
OF ANISALDEHYDE OXIME ESTERS
1
1*
N. A. Zhukovskaya, E. A. Dikusar,
UDC 547.92+547.574.2+
547.362+547.288.4
1
2
V. I. Potkin, and O. G. Vyglazov
Preparative syntheses from anisaldehyde 1 of the anti-isomer of anisaldehyde oxime 2 and anisaldehyde
oxime esters 3a-q in 84-93% yields were developed. The structure—aroma correlation of 2 and 3a-q was
studied.
Key words: anisaldehyde, oxime, carboxylic acids, anhydrides, acid chlorides, esters, aroma analysis, aromas.
The study of aroma—structure relationships of fragments and constituents of natural compounds used in synthesis is
a promising area of fragrance chemistry [1-3]. Oximes of several available natural aldehydes and ketones can act as convenient
synthons for preparing perfumes, aromatic compounds, and biologically active compounds [4-7]. It has been found that just
the presence in fragrances based on oximes of menthone, camphor, jasmorange, veratraldehyde, or citral can cause interaction
with olfactory and gustatory receptors and create the sensation of aroma or taste [3].
The goal of our work was to prepare a homologous series of new esters from the anti-isomer of anisaldehyde oxime
(2). Anisaldehyde oxime esters 3a-q were synthesized by reacting 2 with anhydrides of alkylcarboxylic acids in the presence
of catalystic amounts of HClO (3a-d) or acid chlorides of alkyl-, cycloalkyl-, and arylcarboxylic acids in the presence of
4
pyridine (3e-q). The yields of 3a-q were 84-93%.
O
NOCR
CH NOH
CH
CHO
[RC(O)] O
2
NH OH
2
RC(O)Cl
OMe
OMe
OMe
1
2
3a - q
CH (a), C H (b), CH (CH ) (c), (CH ) CH (d), CH (CH ) (e), (CH ) CHCH (f),
2 2 3 2 2 3 3 2
3
2
5
3
3
2
(CH ) C (g), CH (CH ) (h), CH (CH ) (i), CH (CH ) (j), CH (CH ) (k), CH (CH ) (l),
3 3 2 4 2 5 2 6 2 7 2 8
3
3
3
3
3
cyclo-C H (m), 1-Ad (n), C H (o), CH O (p), C H O (q)
6
11
6
5
3
2 5
The structures of 2 and 3a-q were confirmed by elemental analysis, cryoscopic molecular-weight determination, and
IR and PMR spectra. The purity of the products was 97 1% according to PMR spectroscopy. Elemental analyses and
molecular weights of all synthesized compounds agreed with those calculated.
The Gustation Committee of the Accredited Control-Analytical Laboratory of OOO Tereza-Inter (Moscow) carried
out an organoleptic assessment of the aromas of 2 and 3a-q. Table 1 lists the mean-statistical data for the aromas of the pure
compounds.
1) Institute of Physical Organic Chemistry, National Academy of Sciences, Belarus, 220072, Minsk, ul. Surganova,
13, e-mail: evegn_58@mail.ru; 2) OOO Tereza Inter, Russia, 129110, Moscow, Olimpiiskii prosp., 22, e-mail:
ilb_chuiko@mail.ru. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 131-134, March-April, 2009. Original
article submitted July 25, 2008.
©
0009-3130/09/4502-0148 2009 Springer Science+Business Media, Inc.
148

TABLE 1. Organoleptic Assessment of Aromas of 2 and 3a–q
Compound
Aroma
2
3a
3b
3c
3d
3e
3f
Weak, flowery-berry. Hints of jasmine, narcissus, cranberry, viburnum
Flowery, sweet. Hints of lilac with shades of vanilla-powder
Flowery-fruity. Hints of lilac and rose with shades of red apple
Fruity-berry. Hints of red apple and plum with shades of cranberry and viburnum
Berry. Hints of cranberry and mountain cranberry with shades of flower-vanilla
Berry. Hints of cranberry with shades of vanilla-cream
Berry. Hint of sugary cranberry
3g
3h
3i
Berry. Hint of sugary mountain cranberry
Berry. Aroma of sour viburnum with hint of white wine
Berry. Aroma of ripe viburnum with shades of sweetness
Berry-fruity. Hints of cranberry and blueberry with shades of apple-vanilla
Berry-cream. Hints of blueberry and bilberry with shades of cream-wood
Fruity-creamy. Hints of red apple and plum with shades of vanilla-cream
Fruity-flowery, perfume. Hints of kiwi and cherry with shades of jasmine and gummy rose
Flowery, perfume with light fruity hint. Hints of jasmine, ylang-ylang, and rose with shades of plum-powder
Flowery, perfume. Hints of lilac and jasmine with shades of musk
Flowery. Hints of lilac and flower-of-the-valley with shades of powder
Flowery. Hints of lilac and rose with shades of vanilla-powder
3j
3k
3l
3m
3n
3o
3p
3q
All products were very interesting for possible use in the production of perfumes and food aromas and for use in the
candy and alcohol industries. Compounds 3e-3g, 3j, and 3k were especiallly interesting and promising because they had
distinct and characteristic aromas of berries such as cranberry, blueberry, and bilberry, which are popular and constantly
requested on the food aroma market. Compounds 3e-3g, 3j, and 3k can solve the problem of creating distinct berry aromas for
the food industry becase it is problematical to create aromas similar to the natural aroma of the aforementioned fruits from the
existing assortment of fragrances.
The structure—aroma relationships of the synthesized compounds are interesting. Increasing the alkyl substituent in
3a-3f and 3h-3l converted from flowery to fruity and then to berry aroma with a subsequent intensification of hints of berry-
cream. Substituting alkyl radicals in 3m-3o by cyclic ones produced and strengthened the flowery aroma.
EXPERIMENTAL
IR spectra of the synthesized compounds in thin layers or KBr were recorded on a Protege-460 (Nicolet) IR—Fourier
spectrophotometer. PMR spectra in CDCl solutions (5%) were obtained on a BS-587A (100 MHz, Tesla) spectrometer.
3
Chemical shifts were determined relative to TMS internal standard; molecular weights (MW), by cryoscopy in benzene. The
physicochemical properties of the pure anti-isomer of 2, mp 64-65°C and synthesized from anisaldehyde (1) by the standard
method [6], agree with the literature [8].
Anisaldehyde Oxime Esters 3a-d (general method). The anti-isomer of 2 (0.01 mol) and the anhydride of
the appropriate acid (0.011 mol) were dissolved in anhydrous benzene (30 mL), treated with HClO (47%, 1 drop),
4
stirred, shaken, left at 20-23°C for 24-36 h, diluted with water, and extracted with benzene. The organic layer was separated,
washed with water and NaHCO solution (5%), and dried over CaCl . The solvent was evaporated at reduced pressure
3
2
(p = 10-15 mm Hg) keeping the temperature below 25-30°C. The final purification was carried out by column chromatography
over silica gel L 5/40 μm with hexane eluent.
The following compounds were prepared by this method.
anti-4-Methoxyphenylmethanal-O-acetyloxime (3a). Yield 89%,
20
1.2277, 20 1.5500. C H NO . IR spectrum
nD
10 11 3
d20
−1
(ν, cm ): 3102, 3080, 3040, 3008 (=CH and CH ); 2964, 2938, 2916, 2841 (CH ); 1763 (C=O); 1606 (C=N); 1600, 1573,
Ar
Alk
1513, 1463, 1367 (Ar); 1305, 1259, 1205, 1172, 1112, 1028 (C–O); 835 (CH ).
Ar
PMR spectrum (δ, ppm): 2.10 (s, CH ), 3.72 (s, CH O), 6.65-7.70 (m, C H ), 8.18 (s, HC=N).
3
3
6 4
149

anti-4-Methoxyphenylmethanal-O-propionyloxime (3b). Yield 84%, mp 43-44°C. C H NO . IR spectrum
11 13
3
−1
(ν, cm ): 3098, 3080, 3070, 3055, 3009 (=CH and CH ); 2968, 2970, 2936, 2905, 2880, 2840 (CH ); 1762 (C=O); 1609
Ar
Alk
(C=N); 1600, 1569, 1513, 1460, 1422, 1352 (Ar); 1314, 1257, 1218, 1180, 1073 (C–O); 880, 844, 824 (CH ).
Ar
PMR spectrum (δ, ppm): 1.13 (t, CH ), 2.48 (q, CH ), 3.82 (s, CH O), 6.75-7.75 (m, C H ), 8.27 (s, HC=N).
3
2
3
6 4
anti-4-Methoxyphenylmethanal-O-butyroyloxime (3c). Yield 80%, mp 38-40°C. C H NO . IR spectrum
12 15
3
−1
(ν, cm ): 3100, 3070, 3055, 3009 (=CH and CH ); 2963, 2940, 2900, 2875, 2840 (CH ); 1763 (C=O); 1605 (C=N); 1600,
Ar
Alk
1569, 1512, 1460, 1421, 1360 (Ar); 1305, 1255, 1172, 1136, 1080, 1026 (C–O); 880, 834 (CH ).
Ar
PMR spectrum (δ, ppm): 0.90 (t, CH ), 1.74 (m, CH ), 2.42 (q, CH ), 3.81 (s, CH O), 6.75-7.75 (m, C H ), 8.26 (s,
3
2
2
3
6 4
HC=N).
20
20
n2D0
1.5348. C H NO .
12 15 3
anti-4-Methoxyphenylmethanal-O-isobutyroyloxime (3d). Yield 84%,
1.0374,
d
−1
IR spectrum (ν, cm ): 3100, 3070, 3045, 3009 (=CH and CH ); 2976, 2937, 2915, 2877, 2840 (CH ); 1759 (C=O); 1605
Ar
Alk
(C=N); 1600, 1571, 1515, 1469, 1422, 1387 (Ar); 1312, 1256, 1173, 1128, 1098, 1029 (C–O); 858, 834, 745 (CH ).
Ar
PMR spectrum (δ, ppm): 1.23 [d, (CH ) C], 2.66 (m, CH), 3.77 (s, CH O), 6.70-7.75 (m, C H ), 8.25 (s, HC=N).
3 2
3
6 4
Anisaldehyde Oxime Esters 3e-q (general method). Compound 2 (0.01 mol) was dissolved in anhydrous benzene
(50 mL), treated with anhydrous pyridine (0.01 mol), cooled to 15°C, stirred by carefully shaking, treated with the acid
chloride of the appropriate acid, left at 20-23°C for 24-36 h, diluted with water, and extracted with benzene. The organic layer
was separated, washed with water and NaHCO solution (5%), and dried over CaCl . Solvent was evaporated at reduced
3
2
pressure (p = 10-15 mm Hg) keeping the temperature below 25-30°C. The final purification was carried out by purification
over silica gel L 5/40 μm with hexane eluent.
The following compounds were prepared by this method.
20
20
n2D0
1.5432. C H NO .
13 17 3
anti-4-Methoxyphenylmethanal-O-valeroyloxime (3e). Yield 89%,
1.0026,
d
−1
IR spectrum (ν, cm ): 3100, 3080, 3070, 3040, 3010 (=CH and CH ); 2960, 2934, 2873, 2840 (CH ); 1763 (C=O); 1606
Ar
Alk
(C=N); 1600, 1571, 1514, 1465, 1421, 1346 (Ar); 1311, 1256, 1172, 1144, 1093, 1029 (C–O); 834 (CH ).
Ar
PMR spectrum (δ, ppm): 0.87 (t, CH ), 1.15-1.90 [m, (CH ) ], 2.29 (t, CH ), 3.74 (s, CH O), 6.70-7.65 (m, C H ),
3
2 2
2
3
6 4
8.20 (s, HC=N).
20
20
n2D0
1.5315. C H NO .
13 17 3
anti-4-Methoxyphenylmethanal-O-isovaleroyloxime (3f). Yield 87%,
IR spectrum (ν, cm ): 3100, 3080, 3045, 3004 (=CH and CH ); 2962, 2936, 2918, 2873, 2841 (CH ); 1762 (C=O); 1606
1.0734,
d
−1
Ar
Alk
(C=N); 1600, 1572, 1514, 1465, 1422, 1363 (Ar); 1305, 1285, 1258, 1216, 1172, 1157, 1090, 1029 (C–O); 835 (CH ).
Ar
PMR spectrum (δ, ppm): 0.92 [d, (CH ) C], 1.20-2.60 (m, CH), 2.17 (s, CH ), 3.67 (s, CH O), 6.60-7.65 (m, C H );
3 2
2
3
6 4
8.16 (s, HC=N).
anti-4-Methoxyphenylmethanal-O-pivaloyloxime (3g). Yield 85%, mp 40-41°C. C H NO . IR spectrum
13 17
3
−1
(ν, cm ): 3100, 3080, 3070, 3055, 3040, 3020, 3009 (=CH and CH ); 2977, 2963, 2934, 2870, 2842 (CH ); 1746 (C=O);
Ar
Alk
1607 (C=N); 1600, 1568, 1513, 1460, 1430, 1360 (Ar); 1312, 1259, 1176, 1123, 1109, 1027 (C–O); 889, 832, 835 (CH ).
Ar
PMR spectrum (δ, ppm): 1.29 [s, (CH ) C], 3.81 (s, CH O), 6.75-7.75 (m, C H ), 8.29 (s, HC=N).
3 3
3
6
4
20
20
n2D0
1.5350. C H NO .
14 19 3
anti-4-Methoxyphenylmethanal-O-caproyloxime (3h). Yield 82%,
IR spectrum (ν, cm ): 3100, 3080, 3040, 3007 (=CH and CH ); 2957, 2933, 2871, 2861, 2840 (CH ); 1764 (C=O); 1606
0.9842,
d
−1
Ar
Alk
(C=N); 1600, 1572, 1514, 1465, 1420, 1350 (Ar); 1306, 1257, 1216, 1172, 1144, 1094, 1030 (C–O); 885, 834 (CH ).
Ar
PMR spectrum (δ, ppm): 0.90 (t, CH ), 1.20-1.95 [m, (CH ) ], 2.44 (t, CH ), 3.82 (s, CH O), 6.75-7.75 (m, C H ),
3
2 3
2
3
6 4
8.27 (s, HC=N).
anti-4-Methoxyphenylmethanal-O-enanthyloxime (3i). Yield 80%, mp 49-50°C. C H NO . IR spectrum
15 21
3
−1
(ν, cm ): 3100, 3080, 3045, 3015 (=CH and CH ); 2955, 2945, 2927, 2870, 2857 (CH ); 1763 (C=O); 1610 (C=N); 1600,
Ar
Alk
1572, 1515, 1465, 1418, 1360 (Ar); 1313, 1292, 1254, 1234, 1179, 1137, 1106, 1025 (C–O); 881, 839, 820 (CH ).
Ar
PMR spectrum (δ, ppm): 0.90 (t, CH ), 1.10-2.00 [m (CH ) ], 2.45 (t, CH ), 3.83 (s, CH O), 6.75-7.80 (m, C H ),
3
2 4
2
3
6 4
8.28 (s, HC=N).
anti-4-Methoxyphenylmethanal-O-caprylyloxime (3j). Yield 86%, mp 34-35°C. C H NO . IR spectrum
16 23
3
−1
(ν, cm ): 3099, 3070, 3010 (=CH and CH ); 2953, 2924, 2870, 2856 (CH ); 1763 (C=O); 1606 (C=N); 1600, 1580, 1512,
Ar
Alk
1460, 1420, 1370 (Ar); 1304, 1256, 1172, 1133, 1099, 1026 (C–O); 895, 835 (CH ).
Ar
PMR spectrum (δ, ppm): 0.85 (t, CH ), 1.05-1.97 [m, (CH ) ], 2.41 (t, CH ), 3.79 (s, CH O), 6.75-7.75 (m, C H ),
3
2 5
2
3
6 4
8.24 (s, HC=N).
150

anti-4-Methoxyphenylmethanal-O-pelargonyloxime (3k). Yield 85%, mp 39-40°C. C H NO . IR spectrum
17 25
3
−1
(ν, cm ): 3100, 3080, 3070, 3060, 3040, 3011 (=CH and CH ); 2954, 2926, 2869, 2853 (CH ); 1752 (C=O); 1607 (C=N);
Ar
Alk
1600, 1570, 1511, 1465, 1423, 1380 (Ar); 1310, 1300, 1257, 1224, 1180, 1135, 1114, 1030 (C–O); 897, 832 (CH ).
Ar
PMR spectrum (δ, ppm): 0.88 (t, CH ), 1.12-1.95 [m (CH ) ], 2.45 (t, CH ), 3.84 (s, CH O), 6.65-7.75 (m, C H ),
3
2 6
2
3
6 4
8.28 (s, HC=N).
anti-4-Methoxyphenylmethanal-O-capryloxime (3l). Yield 88%, mp 39-40°C. C H NO . IR spectrum
18 27
3
−1
(ν, cm ): 3100, 3085, 3075, 3060, 3040, 3011, 3011 (=CH and CH ); 2955, 2919, 2869, 2850, 2840 (CH ); 1754 (C=O);
Ar
Alk
1609 (C=N); 1600, 1571, 1514, 1471, 1417, 1379, 1355 (Ar); 1315, 1288, 1256, 1211, 1180, 1135, 1116, 1070, 1057, 1030
(C–O); 897, 845, 832 (CH ).
Ar
PMR spectrum (δ, ppm): 0.86 (t, CH ), 1.20-1.30 [m, (CH ) ], 1.70 (q, CH ), 2.43 (t, CH ), 3.81 (s, CH O), 6.90-
3
2 6
2
2
3
7.66 (m, C H ), 8.27 (s, HC=N).
6
4
anti-4-Methoxyphenylmethanal-O-cyclohexanemethanoyloxime (3m). Yield 90%, mp 83-84°C. C H NO .
15 19
3
−1
IR spectrum (ν, cm ): 3099, 3085, 3070, 3040, 3027, 3009 (=CH and CH ); 2929, 2900, 2853 (CH ); 1737 (C=O); 1607
Ar
Alk
(C=N); 1600, 1570, 1513, 1465, 1449, 1420, 1365 (Ar); 1258, 1202, 1176, 1153, 1119, 1026 (C–O); 831 (CH ).
Ar
PMR spectrum (δ, ppm): 1.20-2.05 (m, C H ), 2.44 (m, CH); 3.82 (s, CH O), 6.90-7.70 (m, C H ), 8.29 (s, HC=N).
6
10
3
6 4
anti-4-Methoxyphenylmethanal-O-(1-adamantane)methanoyloxime (3n). Yield 90%, mp 116-117°C. C H NO .
19 23
3
−1
IR spectrum (ν, cm ): 3097, 3080, 3070, 3055, 3045, 3020, 3006 (=CH and CH ); 2934, 2905, 2885, 2850, 2824 (CH );
Ar
Alk
1736 (C=O); 1606 (C=N); 1600, 1567, 1512, 1453, 1425, 1344 (Ar); 1254, 1207, 1175, 1101, 1057, 1045, 1023 (C–O); 895,
833 (CH ).
Ar
PMR spectrum (δ, ppm): 1.50-2.20 (m, C H ), 3.83 (s, CH O), 6.80-7.75 (m, C H ), 8.30 (s, HC=N).
10 15
3
6 4
anti-4-Methoxyphenylmethanal-O-benzoyloxime (3o). Yield 90%, mp 95-96°C. C H NO . IR spectrum
15 13
3
−1
(ν, cm ): 3097, 3075, 3065, 3045, 3035, 3011 (=CH and CH ); 2970, 2934, 2855, 2840 (CH ); 1735 (C=O); 1607 (C=N);
Ar
Alk
1600, 1571, 1514, 1452, 1422, 1355 (Ar); 1253, 1220, 1173, 1082, 1064, 1025 (C–O); 870, 833, 701, 682 (CH ).
Ar
PMR spectrum (δ, ppm): 3.87 (s, CH O), 6.85-8.25 (m, C H and C H ), 8.49 (s, HC=N).
3
6
4
6 5
anti-4-Methoxyphenylmethanal-O-(methylcarbonate)oxime (3p). Yield 81%, mp 84-85°C. C H NO .
10 11
4
−1
IR spectrum (ν, cm ): 3100, 3088, 3070, 3060, 3040, 3011 (=CH and CH ); 2970, 2958, 2910, 2844 (CH ); 1764 (C=O);
Ar
Alk
1607 (C=N); 1600, 1573, 1514, 1442, 1350 (Ar); 1256, 1180, 1113, 1029 (C–O); 899, 866, 833, 774 (CH ).
Ar
PMR spectrum (δ, ppm): 3.83 (s, CH O), 3.90 (s, CH O), 6.80-7.80 (m, C H ), 8.27 (s, HC=N).
3
3
6 4
20
20
anti-4-Methoxyphenylmethanal-O-(ethylcarbonate)oxime (3q). Yield 84%,
IR spectrum (ν, cm ): 3100, 3075, 3060, 3040, 3010 (=CH and CH ); 2983, 2938, 2912, 2841 (CH ); 1774 (C=O); 1606
1.1099,
1.5440. C H NO .
nD
11 13 4
d20
−1
Ar
Alk
(C=N); 1600, 1573, 1514, 1444, 1422, 1398, 1369, 1347 (Ar); 1304, 1258, 1235, 1173, 1112, 1028 (C–O); 854, 835, 778
(CH ).
Ar
PMR spectrum (δ, ppm): 1.30 (t, CH ), 3.76 (s, CH O), 4.26 (q, CH ), 6.70-7.75 (m, C H ), 8.19 (s, HC=N).
3
3
2
6 4
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