Beruflich Dokumente
Kultur Dokumente
2008; 23: 416425 Published online 20 October 2008 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/ffj.1894
Robert Obara,1 Antoni Szumny,2 Alicja Wzorek,1 Maia Szmigiel-Pieczewska,2 Agata Bialonska,3 Zbigniew Ciunik3 and Czeslaw Wawrzenczyk2*
1 2 3
Institute of Chemistry, Swietokrzyska Academy, Checinska 5, 25-020 Kielce, Poland Department of Chemistry, Wroclaw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroclaw, Poland Faculty of Chemistry, University of Wroclaw, Joliot Curie 14, 50-383 Wroclaw, Poland
ABSTRACT: Starting from g, d-unsaturated terpenoid acids, the corresponding d-iodo-g-lactones and g-iodo-d-lactones were obtained. Dehydrohalogenation of d-iodo-g-lactones with DBU gave unsaturated g-lactones with an exocyclic or alkyl chain double bond. Both types of double bonds possessed the E conguration. The composition of product mixture of dehydrohalogenation strongly depended on the conditions (solvent, temperature) of the process. Odour evaluation of the lactones obtained showed that lactones with two double bonds in the molecule (11 and 12) possess intensive, well-marked, fresh mushroom odours. Lactones with one double bond and one methyl group at C-4 (5a, 6a, 6b and 5d, 6d, 6e) are characterized, in general, by milky, coconut and creamy odours with different notes. Lactones with two methyl groups at C-4 possess herbal (5c, 5f) or woody (6c) odours. Copyright 2008 John Wiley & Sons, Ltd. KEY WORDS: iodolactonization; DBU; elimination; lactones; odour analysis; mushroom odour
Introduction
Lactones, especially terpenoid and sesquiterpenoid ones, are widespread in the plant world.17 They are responsible for the odour of owers2,8 and the odour and taste of fruits912 and vegetables.13,14 Lactones are also present in food. They are known as avour components of alcoholic beverages such as whisky,15,16 sherry17 and wine.18,19 They are also found in bread, dairy and meat products.20 25 Synthetic compounds with a lactone moiety could be seriously considered as good additives in food production.24 Some of them, mainly natural identical products, are used as food additives, e.g. (R)--decanolactone is mixed with margarine to give a avour similar to that of butter.24 The odoriferous and organoleptic properties of - and -lactones and perspectives on their use as fragrance and avour compounds have been the subject of many studies whose results have been presented during the last decade in many papers and review articles.2628 In our research we have also found that some synthetic bicyclic lactones, especially with the p-menthane system, possess interesting and valuable sensory properties.2931 Taking into consideration the above information and encouraged by our own results, we have continued studies in this area. Here we present the synthesis of the next group of unsaturated monocyclic -lactones and their odoriferous characteristics.
* Correspondence to: C. Wawrzenczyk, Department of Chemistry, Wroclaw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroclaw, Poland. E-mail: czeslaw.wawrzenczyk@up.wroc.pl This is no. 31 in a series of papers on lactones.
Experimental
Reagents
Linalool and all other reagents were purchased from the Fluka and Sigma-Aldrich Companies.
Methods
The progress of reactions and the purity of compounds synthesized were checked by thin-later chromatography (TLC) and gas chromatography (GC). TLC was performed on silica gel-coated aluminium plates, using two eluents, hexane:ethyl ether and hexane:acetone in various ratios. The same eluents and methylene chloride were used in the course of preparative column chromatography on silica gel (Kieselgel 60, 230400 mesh). GC analyses were performed on a Varian CP 3380 instrument, using capillary columns: HP-5 [(5% phenyl) methylpolysiloxane], 30 m 0.53 mm i.d., 0.88 m lm thickness; and HP-1 (dimethylpolysiloxane, 25 m 0.32 mm i.d., 0.52 m lm thickness). 1 H-NMR spectra were recorded on a Bruker Avance DRX 300 MHz spectrometer for CDCl3 solutions, with tetramethylsilane (TMS) as the internal standard. The IR spectra were taken for liquid lms or KBr pellets on a FTIR Thermo-Mattson IR spectrometer. Melting points (uncorrected) were measured on a Boetius apparatus.
-axis diffractometer with graphite-monochromated MoK radiation ( = 0.71073 ). Accurate cell parameters were determined and rened by the least-squares method. Data were corrected for Lorentz, polarization and absorption effects. Data reduction and analysis were carried out using the CrysAlice RED program (Oxford Diffraction, 2001).32 Structure was solved by direct methods, using the SHELXS program and rened by the full-matrix least-squares method on all F2 data, using the SHELXL program. All programs used for solution, renement and graphical presentation (TELP) of structures belong to the SHELXTL package (Bruker, 1999).33 Non-hydrogen atoms were rened with anisotropic displacement parameters; H atoms were included in their idealized positions and treated as riding in the subsequent renement, with CH distances in the range 0.951.00 and with Uiso(H) = 1.2 Ueq(C).
KOH (75 cm3, 5%) and the mixture was reuxed for 10 h. Then ethanol was evaporated and the residue was diluted with water. Organic impurities were extracted with ethyl ether and then the aqueous solution was acidied (pH 4.0) with 0.1 M HCl. The product was extracted with ethyl ether. The ethereal solution was washed with brine and dried over MgSO4. After evaporation of solvent, the pure acid (3.3 g, 97% yield) was obtained. Its physical and spectral data were: nD20 = 1.4362; 1H-NMR (CDCl3) : 0.76 and 0.78 (d, J = 6.6 Hz, 6H, -CH(CH3)2), 0.97 (d, J = 6.7 Hz, 3H, -CH(CH3)-), 1.49 (m, 1H, -CH(CH3)2), 1.77 (t, J = 6.6 Hz, 2H, -CH2CH =), 2.25 (m, 2H, -CH2CO2-), 2.57 (m, 1H, -(CH)CH3)-), 5.26 (dd, J = 15.3 and 7.0 Hz, 1H, CH2CH=CH-), 5.36 (dt, J = 15.3 and 6.6 Hz, 1H, -CH2CH=CH-), 10.0 (br. s, -COOH); IR (lm, cm1): 26003200 (s,b), 1726 (s), 976 (s). Iodolactonization of (E)-3,7-dimethyl-4-octenoic acid ( 2 ). Aqueous solution of NaHCO3 (60 cm3, 0.5 M) was added to a solution of acid 2 (3.3 g, 0.019 M) in 60 cm3 ethyl ether and the mixture was stirred at room temperature for 30 min and then reuxed. To a reuxing mixture, a solution of iodine (7.8 g) and KI (15.3 g) in 100 cm3 water was slowly added. The mixture was stirred under reux for 10 h. After cooling the mixture was diluted with ethyl ether and Na2S2O3 aqueous solution was added until the mixture became colourless. Then ethereal solution was separated and washed with NaHCO3 solution, brine, and dried (Na2SO4). After solvent evaporation of the crude product (4.8 g, yield 84%), a mixture of four iodolactones was obtained. Separation by column chromatography on silica gel using two different eluents afforded pure products. When a mixture of hexane:ethyl acetate (9:1) was used, two lactones were separated: cis--iodo--lactone (3a, Rf = 0.32) and cis,trans--iodo--lactone (4a, Rf = 0.23). Next two iodolactones, trans--iodo--lactone (3b, Rf = 0.44) and trans,trans-iodo--lactone (4b, Rf = 0.34) were separated when methylene chloride was applied as eluent. The amounts of lactones obtained and their contents in the product mixture (calculated from amounts of each lactone isolated), physical and spectral data are as follows:
Odour evaluation
Odoriferous characterization of the lactones synthesized was carried out by a group of perfumers from the Technical University of Ld, under the direction of Professor J. Gra and Professor J. Kula. The odour evaluation was performed for ethanolic solution (10%) of samples (98% purity according to GC) with the use of a strip blotter.
Scheme 1.
cis-4-Methyl-5-(1-iodo-3-methylbutyl)tatrahydrofuran-2one (cis--iodo--lactone, 3a): white crystals (2.75 g, 57%); m.p. 7576 C, 1H-NMR (CDCl3) : 0.88 and 0.97 (two d, J = 6.4 Hz, 6H, -CH(CH3)2), 1.03 (d, J = 6.7 Hz, 3H, -CH(CH3)-), 1.75 (m, 2H, -CH2CHI-), 1.85 (m, 1H, -CH(CH3)2), 2.28 (d, J = 16.2 Hz, 1H, one of CH2-3), 2.772.85 (two m, 2H, one of CH2-3, CH(CH3)-), 3.88 (m, 1H, -CHI-), 4.51 (dd, J = 11.0 and 4.2 Hz, 1H, H-5); IR (KBr, cm1): 1796 (s), 1172 (s), 1076 (m). Crystal data for 3a: C10H17O2I, M = 296.14, colourless block, crystal dimensions 0.15 0.10 0.10 mm, monoclinic, space group P21/n, a = 10.322(2), b = 7.0240(10), c = 15.430(3) , = 91.75(3), V = 1118.2(3) 3, Z = 4, Dc = 1.759 mg m3, T = 100(2) K, R = 0.0283, Rw = 0.0785 (2335 reections, all data) for 119 variables. CCDC 674714. trans-4-Methyl-5-(1-iodo-3-methylbutyl)tetrahydrofuran-2one (trans--iodo--lactone, 3b): colourless liquid; (1.5 g, 32%); 20 = 1.5082; 1H-NMR (CDCl3) : 0.84 and 0.98 (two d, nD J = 6.5 Hz, 6H, -CH(CH3)2, 1.25 (d, J = 7.0 Hz, 3H, -CH(CH3)-), 1.45 (ddd, J = 14.5, 9.6 and 3.6 Hz, 1H, one of CH2CHI-), 1.78 (ddd, J = 14.5, 11.1 and 3.7 Hz, 1H, one of CH2CHI-), 1.88 (m, 1H, -CH(CH3)2), 2.17 (dd, J = 18.1 and 5.7 Hz, 1H, CH2-3), 2.59 (m, 1H, -CH(CH3)-), 2.87 (dd, J = 18.1 and 9.7 Hz, 1H, one of CH2-3), 3.90 (dd, J = 5.9 and 4.4 Hz, 1H, H-5), 4.22 (ddd, J = 11.1, 5.9 and 3.6 Hz, 1H, -CHI-); IR (lm, cm1): 1796 (s), 1192 (s), 1024 (s). cis,trans-4-Methyl-5-iodo-6-(2-methylpropyl)tetrahydro-2Hpyran-2-one (cis,trans--iodo--lactone, 4a): oily liquid; (0.15 g, 3%); 1H-NMR (CDCl3) : 0.86 and 0.96 (two d, J = 6.6 Hz, 6H, -CH(CH3)2), 1.20 (d, J = 6.8 Hz, 3H, -CH(CH3)-), 1.40 (ddd, J = 14.2, 8.8 and 4.6 Hz, 1H, one of (CH3)2CHCH2-), 1.86 (m, 1H, -CH(CH3)2, 2.00 (ddd, J = 14.2, 10.8 and 4.8 Hz, 1H, one of CH2CH(CH3)2), 2.21 (dd, J = 17.8 and 7.7 Hz, 1H, one of CH2-3), 2.54 (m, 1H, -CH(CH3)-), 2.84 (dd, J = 17.8 and 9.2 Hz, 1H, one of CH2-3), 3.61 (dd, J = 6.0 and 2.4 Hz, 1H, -CHI-), 4.21 (ddd, J = 10.8, 4.6 and 2.4 Hz, 1H, H-6); IR (cm1): 1748 (s), 1172 (s), 1140 (s), 1012 (s). trans,trans-4-Methyl-5-iodo-6-(2-methylpropyl)tetrahydro2H-pyran-2-one (trans--iodo--lactone, 4b): white crystals; (0.4 g, 8%); m.p. 4950 C, 1H-NMR (CDCl3) : 0.92 and 0.93 (two d, J = 6.4 Hz, 6H, -CH(CH3)2), 1.18 (d, J = 6.6 Hz, 3H, CH(CH3)-), 1.55 (m, 1H, -CH(CH3)2), 1.912.01 (m, 2H, -CH2CH(CH3)2), 2.15 (dd, J = 17.0 and 9.4 Hz, 1H, one of CH2-3), 2.37 (m, 1H, -CH(CH3)-), 2.74 (dd, J = 17.0 and 5.7 Hz, 1H, one of CH2-3), 3.61 (dd, J = 10.4 and 9.5 Hz, 1H, -CHI-), 4.53 (td, J = 10.4 and 1.6 Hz, 1H, H-6); IR (cm1): 1740 (s), 1240 (s), 1144 (s), 1036 (s).
isolated yields are given in Table 1. The physical and spectral data of the unsaturated lactones obtained are given below. (E)-4-Methyl-5-(3-methylbutylidene)tetrahydrofuran-2-one (5a): 20 = 1.4572; 1H-NMR (CDCl3) : 0.91 and colourless liquid; nD 0.93 (two d, J = 6.6 Hz, 6H, -CH(CH3)2), 1.23 (d, J = 7.1 Hz, 3H, -CH(CH3)-), 1.571.97 (three m, 3H, -CH2CH(CH3)2), 2.27 (dd, J = 17.9 and 2.3 Hz, 1H, one of CH2-3), 2.87 (dd, J = 17.9 and 9.3 Hz, 1H, one of CH2-3), 3.20 (m, 1H, -CH(CH3)-), 5.16 (td, J = 8.7 and 1.3 Hz, 1H, -CH2-CH=); IR (lm, cm1): 1816 (s), 1700 (s), 1144 (s), 1012 (s). cis-4-Methyl-5-(3-methyl-(1E)-buten-1-yl)tetrahydrofuran-2-one 20 = 1.4545; 1H-NMR (CDCl3) : 1.01 (6a): colourless liquid; nD (d, J = 6.9 Hz, 3H, CH(CH3)-), 1.02 (d, J = 6.7 Hz, 6H, -CH(CH3)2), 2.202.70 (four m, 4H, CH2-4, -CH(CH3)-, -CH(CH3)2), 4.90 (t, J = 6.7 Hz, 1H, H-5), 5.40 (ddd, J = 15.5, 7.4 and 1.4 Hz, 1H, -CH=CHCH(CH3)2), 5.78 (ddd, J = 15.5, 6.5 and 0.9 Hz, 1H, CH=CHCH(CH3)2); IR (lm, cm1): 1788 (s), 1676 (w), 1176 (s), 972 (s). trans-4-Methyl-5-(3-methyl-(1E)-buten-1-yl)-tetrahydrofuran20 = 1.4522; 1H-NMR (CDCl3) 2-one (6b): colourless liquid, nD : 0.98 (d, J = 6.8 Hz, 6H, -CH(CH3)2), 1.09 (d, J = 6.4 Hz, 3H, -CH(CH3)-), 2.132.33 (three m, 3H, -CH(CH3)-, -CH(CH3)2, one of CH2-3), 2.65 (m, 1H, one of CH3-3), 4.32 (t, J = 7.8 Hz, 1H, H-5), 5.36 (ddd, J = 15.4, 7.8 and 1.4 Hz, 1H, -CH=CH-CH(CH3)2), 5.78 (ddd, J = 15.4, 6.5 and 0.8 Hz, 1H, -CH=CH-CH(CH3)2); IR (KBr, cm1): 1792 (s), 1216 (s), 1172 (s), 966 (s). (E)-4,4-Dimethyl-5-(3-methylbutylidene)-tetrahydrofuran-2-one 20 = 1.4608; 1H-NMR (CDCl3) : 0.86 (5c): colourless liquid; nD (d, J = 6.7 Hz, 6H, -CH(CH3)2), 1.34 (s, 6H, -C(CH3)2-), 1.57 (m, 1H, -CH(CH3)2), 1.93 (dd, J = 7.9 and 7.0 Hz, 2H, -CH2CH=), 2.47 (s, 2H, -CH2CO2-), 5.07 (t, J = 7.9 Hz, 1H, -CH2CH=); IR (cm1): 1792 (s), 1472 (m), 1236 (m), 1092 (m). 4,4-Dimethyl-5-(3-methyl-(1E)-buten-1-yl))-tetrahydrofuran-220 = 1.4541; 1H-NMR (CDCl3) : one (6c): colourless liquid; nD 1.01 (d, J = 6.8 Hz, 6H, -CH(CH3)2), 1.14 (s, 6H, -C(CH3)2, 2.37 (m, 1H, -CH(CH3)2), 4.46 (d, J = 7.7 Hz, 1H, >CHO-), 5.39 (ddd, J = 15.5, 7.7 and 1.3 Hz, 1H, (CH3)2CHCH=CH-), 5.79 (ddd, J = 15.5, 6.6 and 0.9 Hz, 1H, (CH3)2CHCH=CH); IR (lm, cm1): 1792 (s), 1472 (s), 1380 (s), 1292 (s), 1236 (s), 1172 (s). (E)-4-Methyl-5-(3,3-dimethyl-1-butylidene)-tetrahydrofuran-220 = 1.4588; 1H-NMR (CDCl3) : one (5d): colourless liquid; nD 0.88 (s, 9H, -C(CH3)3), 1.20 (d, J = 7.1 Hz, 3H, -CH(CH3)-), 1.86 (d, J = 8.2 Hz, 2H, -CH2-CH=), 2.24 (dd, J = 17.9 and 1.9 Hz, 1H, one of CH2-3), 2.83 (dd, J = 17.9 and 9.3 Hz, 1H, one of CH2-3), 3.16 (m, 1H, -CH(CH3)-), 5.18 (td, J = 8.2 and 1.3 Hz, 1H, -CH2-CH=); IR (lm, cm1): 1812 (s), 1708 (s), 1592 (m), 1160 (s), 1128 (s). cis-4-Methyl-5-(3,3-dimethyl-(1E)-buten-1-yl)tetrahydrofuran20 = 1.4535; 1H-NMR (CDCl3) 2-one (6d): colourless liquid; nD : 0.97 (d, J = 6.9 Hz, 3H, -CH(CH3)-), 1.01 (s, 9H, -C(CH3)3), 2.20 (dd, J = 19.8 and 9.2 Hz, 1H, one of CH2-3), 2.61 (m, 1H, -CH(CH3)-), 2.64 (dd, J = 19.8 and 7.9 Hz, 1H, one of CH2-3), 4.88 (m, 1H, H-5), 5.32 (dd, J = 15.7 and 7.5 Hz, 1H, -CH=CH-CH<),
Dehydrohalogenation procedure
1.8-Diazabicyclo[5.4.0]undec-7-ene (DBU) (0.015 M) was added to a solution of -iodo--lactone (0.01 M) in 50 cm3 dichloromethane or benzene and the reaction mixture was stirred at room temperature (CH2Cl2) or under reux (benzene) for 4 150 h. Then the reaction mixture was diluted with ethyl ether (100 cm3), washed with water and dried with MgSO4. The crude products were puried by column chromatography (silica gel, hexane:ethyl acetate 8:1, or hexane:diethyl ether 2:1). The solvent, time of reaction, composition of product mixtures, and
Table 1. The reaction conditions and results of dehydrohalogenation of -iodo--lactones Temperature (C) Time (h) Products (%) Total isolated yield (%)
Copyright 2008 John Wiley & Sons, Ltd. Reux Reux R.t. 8 48 24 5a 75 42 85 6a 25 58 15 90 86 77 Reux R.t. 8 48 5a 44 62 6b 56 38 88 69 Reux R.t. Reux R.t. Reux R.t. 48 140 6 150 48 72 5c 70 65 58 41 81 60 6c 30 35 42 59 19 40 92 84 90 83 93 85
Substrate
Solvent
3a
3b
Benzene CH2Cl2
3c
Copyright 2008 John Wiley & Sons, Ltd. Reux R.t. 12 24 5d 72 100 6d 28 92 88 5d Reux R.t. 12 24 50 67 6e 50 33 86 82 Reux R.t. 1 8 5f 100 100 93 92
Substrate
Solvent
3d
Benzene CH2Cl2
3e
Benzene CH2Cl2
3f
Benzene CH2Cl2
5.79 (dd, J = 15.7 and 1.0 Hz, 1H, -CH=CH-CH<); IR (lm, cm1): 1780 (s), 1668 (m), 1216 (s), 1160 (s), 972 (s). trans-4-Methyl-5-(3,3-dimethyl-(1E)-buten-1-yl)tetrahydrofuran2-one (6e): white solid; m.p. 3738 C; 1H-NMR (CDCl3) : 1.01 (s, 9H, -C(CH3), 1.08 (d, J = 6.4 Hz, 3H, -CH(CH3)-), 2.132.27 (two m, 2H, -CH(CH3)-, one of CH2-3), 2.65 (m, 1H, one of CH2-3), 4.32 (dd, J = 7.9 and 7.6 Hz, 1H, H-5), 5.32 (dd, J = 15.6 and 7.6 Hz, 1H, -CH=CH-CH<), 5.80 (dd, J = 15.6 and 0.8 Hz, 1H, -CH=CHCH<): IR (KBr, cm1): 1780 (s), 1216 (s), 1164 (s), 972 (s). (E)-4,4-Dimethyl-5-(3,3-dimethyl-1-butylidene)-tetrahydrofuran2-one (5f): white crystals; m.p. 5758 C; 1H-NMR (CDCl3) : 0.92 (s, 9H, (CH3)3C-), 1.41, 1.56 (two s, 6H, -(CH3)2C-), 2.01 (d, J = 8.0 Hz, 2H, -CH2-CH=), 2.54 (s, 2H, -CH2-CO2-), 5.20 (t, J = 8.0 Hz, 1H, -CH2-CH=); IR (KBr, cm1): 1780 (s), 1688 (s), 1240 (s), 1080 (s).
(Z)-5-(1.5-Dimethyl-4-hexen-1-ylidene)dihydrofuran-2-one 20 = 1.4905; 1H-NMR (CDCl3) : (11): colourless liquid; nD 1.65 and 1.57 (two s, 6H, =C(CH3)2-), 1.68 (s, 3H, =C(CH3)-), 1.92 (m, 2H, -CH2CH2CH=), 2.14 (m, 2H, -CH2CH2CH=), 2.62 (m, 2H, -C(O)-CH2CH2), 2.70 2.81 (m, 2H, -C(O)CH2-), 5.07 (t, 1H, J = 6.8 Hz, -CH=C(CH3)2); IR (lm, cm1): 1800 (s), 1711 (s), 1123 (m), 1079 (m). (E)-5-(1.5-Dimethyl-4-hexen-1-ylidene)dihydrofuran-2-one 20 ( 12): colourless liquid; nD = 1.4920; 1H-NMR (CDCl3) : 1.56 (s, 3H, =C(CH3), 1.65 and 1.57 (two s, 2H, =C(CH3)2), 2.13 (m, 2H, -CH2CH2CH=), 2.01 (m, 2H, -CH2CH2CH=), 2.582.63 (m, 2H, -C(O)-CH2CH2-), 2.732.78 (m, 2H, -C(O)CH2-), 5.05 (t, 1H, J = 5.7 Hz, -CH=C(CH3)2); IR (lm, cm1): 1802 (s), 1711 (s), 1123 (m), 1074 (m).
Figure 1.
The structure of 3a was also conrmed by X-ray analysis. The X-ray crystal structure (Figure 1) showed the cis orientation of methyl and 1-iodo-3-methylbutyl groups in this molecule. The coupling constant between H-4 and H-5 (J = 4.1 Hz) is in accordance with the value of the torsion angle between bonds of these protons (30) from the X-ray structure. The mixture of unsaturated lactones with exocyclic double bond, 5a, 5c, 5d and with a double bond in the alkene substituent, 6ae or 5d and 5f as only products were obtained in the dehydrohalogenation process of respective iodolactones with 1.8-diazabicyclo[5.4.0] undec7-ene (DBU) (Scheme 2). The conditions of the reactions, composition of product mixtures and the isolated yields are presented in Table 1. The composition of product mixtures depended on the conditions of the reaction (solvent and temperature) and,
in the highest extent, on the structure of iodolactones. Studies on the inuence of the conditions of the reaction on the kind of the products of dehydrohalogenation were carried out on the dehydrohalogenation of iodolactone 3c. The experiments carried out indicated that the results of reactions in ethyl ether and in methylene chloride are similar. The dehydrohalogenation of 3c carried out at different temperatures indicated that at a higher temperature products with double bonds in the exocyclic position were formed preferentially over products with a double bond in the alkane chain, in the , position to the lactone ring. The dehydrohalogenation experiments for the next iodolactones were carried out in reuxed benzene or in methylene chloride at room temperature. Analysis of the results presented in Table 1 indicates that, except for the experiment of dehydrohalogenation of iodolactone 3e in reuxing benzene, the reaction of lactones with the 1-iodo-3,3-dimethylbutyl substituent afforded lactones with exocyclic double bonds (5d and 5f ) as the main or only products. The composition of product mixtures of dehydrohalogenation of lactones with the 1-iodoisobutyl group depended on both the solvent and the temperature of the reaction. The reactions carried out for the iodolactones with one methyl group at C-4 in reuxed benzene afforded, predominantly, unsaturated lactones with a double bond in the ,-position to the lactone ring, whereas the reaction carried out in methylene chloride at room temperature gave mainly a product with a double bond in the exocyclic position. The position of the double bond in the product of dehydrohalogenation of isomeric (cis,trans) iodolactones 3a and 3b as well as 3d and 3e depended on the relative arrangement of methyl and iodoalkyl groups. The mixture of products obtained from cis isomers (3a and 3d) contained more lactones with exocyclic double bonds (5a and 5d, respectively) than product mixtures obtained from the dehydrohalogenation of trans isomers (3b and 3e). This was especially visible when the reaction was carried out in methylene chloride. These results can be explained
Scheme 3.
by the easier approach of bulky base to the eliminated lactone proton. The structures of products were established on the basis of 1H-NMR and IR data. Absorption bands in the range 17801816 cm1 found in the IR spectra conrmed that the -lactone ring was not affected by the reaction with DBU. Multiplets of olen protons of lactones with exocyclic double bonds were located at 5.075.20 p.p.m. in the 1HNMR spectra. The E conguration of double bond in these products could be deduced by taking into account the structure of iodolactones and stereochemical requirements of the E-2 elimination reaction. (Scheme 3). The CI and CO bonds (of the lactone ring) in the iodolactones, according to the mechanism of halolactonization,37,38 are trans-orientated (A) and thus the CI and CH5 bonds are in the cis-relation. The E-2 elimination of the iodine and H-5 atoms meanwhile requires their antiperiplanar conformation. The dihedral angel C5H and CI bond found from crystallographyc data is 68. So, for the dehydrohalogenation process of iodolactones studied, the rotation around the C-5 of the lactone ring and C-1 of the alkyl substituent bond to the arrangement, as in (B), is necessary. In this way the E conguration of the resulting exocyclic double bond in lactones (C) could be proposed. The E conguration of the exocyclic double bond was proved by one-dimensional nuclear Overhauser effect (1D-NOE) spectroscopy. The NOE effects between the protons of the CH3 groups at the C-4 and CH2-3 in the lactone ring, as well as the protons of the methylene group (CH2-2) in the alkyl chain, were clearly observed in the spectra of lactones 5a and 5d. In the spectra of lactones with a double bond in the ,-position to the lactone ring, olene protons usually gave signals in the region 5.40 5.75 p.p.m. Their multiplicity depends on the number of hydrogen atoms at neigh-
bouring carbon atoms. The value of coupling constants between olen protons (J = 15.515.7 Hz) undoubtly conrms the E conguration of double bonds formed in the alkyl chain. The unsaturated lactones with two double bonds in the molecule were obtained in a two-step synthesis from a diastereoisomeric (E/Z) mixture of the known36 acid 7 (Scheme 4). This acid was obtained by us from linalool via its Claisen rearrangement with triethylorthoacetate, followed by alkaline hydrolysis of ,-unsaturated esters formed.39 The iodolactonization of acid 7 afforded the mixture (according to GC) of of isomeric -iodo--lactones (33% of 8 and 33% of 9) and 34% of -iodo--lactone (10). The separation of these iodolactones by column chromatography afforded the pure -iodo--lactone (10) and an inseparable (by this method) mixture of iodolactones (8 and 9). The dehydrohalogenation of this mixture with DBU gave an equimolar mixture of isomeric (Z and E) unsaturated lactones, 11 and 12, respectively. The congurations of the exocyclic double bonds in these products were assigned taking into account the chemical shifts of the methyl group at C-1 and the methylene group (CH2-2) of the isoprenoid substituent. The closer position of the methyl group to the lactone oxygen atoms (isomer E) causes that singlet of these protons to be located in the 1H-NMR spectrum at a lower eld ( = 1.68) than a singlet of this group in the spectrum of isomer Z ( = 1.56). The multiplets of protons of CH2-2 of isomers Z and E are situated contrariwise in the 1H-NMR spectrum. This multiplet was found at a higher eld ( = 1.92) in the spectrum of isomer E and at a lower eld ( = 2.13) in the spectrum of isomer Z. All unsaturated lactones obtained were subjected to evaluation of their odours. The odoriferous characteristics of the lactones obtained are presented in Table 2.
Scheme 4.
Table 2.
Compound
Weak, coconut-creamy 5a 5d
Intense, creamy with fruity note 6a Intense, coconut-vanilla with apricot note 6d
Intense, coconut-creamy
Intense, coconut-woody
11
The variety of structures of lactones studied allowed us to analyse the odourstructure relationship. Lactones with two double bonds in the molecule (11 and 12) possess intensive, well-marked, fresh mushroom odours. Lactones with one double bond and one methyl group at C-4 (5a, 6a, 6b and 5d, 6d, 6e) are characterized, in general, by milky, coconut and creamy odours with different notes. Lactones with two methyl groups at C-4 possess herbal (5c, 5f ) or woody (6c) odours. Analysis of the inuence of the place of the double bond in the molecule on the odour of a compound indicated two dependences: rst, the intensity of odours; and second, the note. The odours of lactones with an exocyclic double bond, except compounds with two double bonds (11, 12), are rather weak, whereas lactones with a double bond in the ,-position to the ring possess intensive odours. Comparison of the odours of lactones 5c and 6c also showed the change of kind of odour with the position of the double bond; the rst is characterized by a herbal odour, whereas the second has a woody odour. Comparative analysis of the odours of isomeric (cis/ trans) lactones 6a and 6b or 6d and 6e also indicates a signicant difference. The cis isomers posses creamy (6a) and coconut-creamy (6d) odours, whereas the respective trans isomers have coconut-vanilla (6b) or coconutwoody (6d) odours. The odours of isomeric lactones with two double bonds are differentiated only by notes: fruity in isomer Z (11) and forest in isomer E (12). In our opinion, lactones 11 and 12 have the chance to be applied as food additives. It is worth noticing that a mixture of these compounds also has an outstanding fresh mushroom odour.
References
1. 2. 3. 4. 5. 6. 7. Pisarski B, Wawrzenczyk C. Lactones 30. Tetrahedr. Lett. 2006; 46: 68756877. Ohloff G. Scent and Fragrances. Springer-Verlag: Berlin, 1992; 182189. Parliament TH, McGorrin RJ. Flavour Chemistry, Risch SJ, Chi-Tang H (eds). American Chemical Society: Washington, DC, 2000; 76 78. Takahashi K, Someya T, Muraki S et al. Agric. Biol. Chem. 1980; 44: 15351543. Nf R, Velluz A. Flavour Fragr. J. 1998; 13: 203208. Fraga BM. Nat. Prod. Rep. 2006; 23: 943972. Asakawa Y, Toyota M, Nagashima F et al. Heterocycles 2001; 54: 10571093.
8. Onayade OA, Looman AMG, Scheffer JJC et al. Flavour Fragr. J. 1988; 13: 409412. 9. Gomez E, Ledbetter CA. J. Sci. Food Agric. 1997; 74: 541 546. 10. Yamamoto T. In Current Topics in Flavours and Fragrances: Towards a New Millennium of Discovery, Swift KAD (ed.). Kluwer Academic: London, UK, 1999; 5556. 11. Mosandl A. In Flavourings, Ziegler H, Ziegler E (eds). Wiley VCH, Weinheim, Germany, 1998; 604609. 12. Kitaura T, Endo H, Nakamoto H et al. Flavour Fragr. J. 2004; 19: 221224. 13. Ruiz Del Castillo ML, Herraiz M, Blanch GP. J. Agric. Food Chem. 2000; 48: 11861190. 14. Naito T, Katsuhara T, Niitsu K et al. Heterocycles 1991; 32: 24332442. 15. Wilkinson KL, Elsey GM, Prager RH et al. J. Agric. Food Chem. 2004; 52: 42134218. 16. Ebata T, Matsumoto K, Yoshikoshi H et al. Heterocycles 1993; 36: 10171026. 17. Moreno JA, Zea L, Moyano L et al. Food Control 2005; 16: 333 338. 18. Guth H. Helv. Chim. Acta 1996; 79: 15591571. 19. Guth H. J. Agric. Food Chem. 1997; 45: 30223026. 20. Peterson DG, Reineccius GA. Flavour Fragr. J. 2003; 18: 320 324. 21. Belitz HD, Grosch W, Schieberle P. Aroma Substances in Food Chemistry. Springer-Verlag: Berlin, 2004; 362365. 22. Alewijn M, Smith, BA, Sliwinski EL et al. Int. Dairy J. 2007; 17: 5966. 23. Macleod G. In Flavour of Meat, Meat Products and Seafoods. Blackie Academic & Professional: London, UK,1998; 62. 24. Pintauro N. In Flavor Technology. Noyes Data Corp. (NDC): Park Ridge, NJ, 1971; 8991. 25. Mottram DS, Edwards RA, Mace HA. J. Sci. Food Agric. 1982; 33: 934944. 26. Zope DD, Patnekar SG, Kanetkar VR. Flavour Fragr. J. 2006; 21: 395399. 27. Frater G, Bajgrowicz JA, Kraft P. Tetrahedron 1998; 54: 7633 7703. 28. Kuentzel H, Bahri H. In Food Flavorings, 3rd edn, Ashurst P (ed.). SpringerVerlag: Berlin, 1999; 120141. 29. Dams I, Bialonska A, Ciunik Z et al. J. Agric. Food Chem. 2004; 52: 16301634. 30. Paruch E, Wawrzenczyk C. Proceedings of the Second National Symposium on Natural and Synthetic Fragrance Materials, Agro Food Technology, Czeladz, 1999; 121133. 31. Grabarczyk M, Gra J, Wawrzenczyk C. Polish Patent No. 194471, 2007. 32. Oxford Diffraction. CrysAlis CCD and CrysAlis RED, Oxford Diffraction (Poland) Sp. z o.o.: Wroclaw, Poland, 2001. 33. Bruker AXS. SHELXTL-NT v. 5.1 1999. 34. Obara R, Szumny A, Zolnierczyk A et al. Pol. J. Chem. 2005; 79: 981993. 35. Wawrzenczyk C, Przepirka Z, Zabza A. Pol. J. Chem. 1981; 55: 819825. 36. Baeckstrom P, Li L. Tetrahedron 1991; 47: 65216532. 37. Mori K, Nakazono Y. Tetrahedron 1986; 42: 283290. 38. Ranganathan S, Muraleedharan KM, Vaish NK et al. Tetrahedron 2004; 60: 52735308. 39. Szumny A, Wawrzenczyk C, Nagielska A. Polish Patent Nos 197586 and 197573, 2007.