The Separation and Synthesis of Lipidic 1,2-And 1,3-Diols From Natural Phenolic Lipids For The Complexation and Recovery of Boron

Chemistry and Physics of Lipids 126 (2003) 177199
The separation and synthesis of lipidic 1,2- and 1,3-diols from natural phenolic lipids for the complexation and recovery of boron
John H.P. Tyman , Satinderjit K. Mehet
Department of Chemistry, Brunel University, Uxbridge, Middlesex UB8 3PH, UK Received 17 April 2003; received in revised form 25 July 2003; accepted 13 August 2003
Abstract A study has been made of the semi-synthesis of 1,3-diols (anacardic alcohols) from natural phenolic lipid resources from Anacardium occidentale and Anacardium giganteum which have given C15 and C11 derivatives, respectively. An isomeric 1,3-diol (isoanacardic alcohol) has been obtained from cardanol separated from technical cashew nut-shell liquid. Homologous1,3-diols have been synthesised from a range of synthetic 2-alkyl-, 3-alkyl- and 4-alkylphenols and from 6-alkylsalicylic acids. The natural 1,2-diol, urushiol, from Rhus vernicifera has been puried. All these lipidic compounds have been studied for their complexation and the potential recovery of boron as boric acid. 2003 Elsevier Ireland Ltd. All rights reserved.
Keywords: Alkyl- and arylalkyl-1,3-diols; Alkylsalicyl alcohols; Saligenins; Aryl-1,2-diols; Boric acid complexation; Solvent extraction of boron compounds
1. Introduction The interaction between polyhydroxy compounds and boric acid has been of interest since the classical conductometric work on the absolute conguration of glycols and of the - and -glucoses (Boesekin, 1913). More recent experimental work has concentrated on the complexation and extraction of boric acid by monohydric alcohols, such as isoamyl alcohol (Vinogradov, 1962), 2-ethylhexanol (Brown and Sanderson, 1978a, Vinogradov et al.,
Long Chain Phenols, Part 38. Corresponding author. Tel.: +44-20-8878-6314; fax: +44-20-8878-6314. E-mail address: jhptyman@hotmail.com (J.H.P. Tyman).
2001), and notably by lipidic diols, 2-ethylhexane1,3-diol (Brown and Sanderson, 1978b), nonane1,3-diol, decane- and dodecane-1,3-diols (Shvarts et al., 1995; Svares et al., 1983), and in the aromatic o-hydroxymethylphenolic (alkylsalicyl alcohol) series, with 2-chloro-6-hydroxymethyl-4isooctylphenol (Brown and Sanderson, 1978b). Some of these studies have led to commercial interest in the prospect of recovery through solvent extraction as, for example, by the American Potash and Chemical Corporation (Havighorst, 1963; Klopfenstein and Arnold, 1966), with octylchlorosaligenin, 2-chloro6-hydroxymethyl-4-t-octylphenol (OCS) for the recovery of boric acid from Californian salt lake brines having borate concentrations below those applicable to conventional recovery by crystallisation In other
0009-3084/$ see front matter 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.chemphyslip.2003.08.004
178
J.H.P. Tyman, S.K. Mehet / Chemistry and Physics of Lipids 126 (2003) 177199
Fig. 1. Formulae of phenolic lipids and structures of unsaturated side chains b, c, d of 1, 3 and b, c, d, e of 4.
cases, where boron contamination is undesirable, for example, in agricultural citrus crop cultivation, or in magnesium production (Folkestad et al., 1972), solvent extraction involving 2-ethylhexanol and isooctanol in petroleum ether has found a role in the selective recovery/removal of boric acid. In the present preparative work, amongst the replenishable raw materials used for the semi-synthesis of lipidic 1,3-diols, anacardic acid (1) (n = 0, 2, 4, 6) is the chief C15 component of natural cashew nut-shell liquid (Tyman, 1979, 1996), in Anacardium occidentale indigenous to India and Brazil and (2) the C11 analogue in Anacardium giganteum. In the industrial heat-processing of cashew, the technical cashew nut-shell liquid formed by decarboxylation contains mainly the by-product, cardanol (3) (n = 0, 2, 4, 6). Urushiol (4) (n = 0, 2,
4, 6) is the major aromatic C15 3-alkenyl-1,2-diol in Rhus vernicifera (from Japan and China) and in Rhus toxicodendron (Tyman, 1979, 1996). The natural isomeric 4-alkenyl analogue, thitsiol, occurs in the Burmese lac tree, Melanorrhea usitata. Fig. 1 depicts the structures of the rst four materials. Anacardic acid (1) and cardanol (3) have unsaturated side chains (b, c and d) while urushiol (4) has unsaturated structures (b, c, d and e) (Fig. 1). Fossil fuel-derived 4-t-butyl, 4-t-nonyl, and 4t-octylphenol have served as starting materials for the synthesis of analogous saligenins, with 2hydroxymethylphenolic structures. The compounds synthesised, namely 2-hydroxymethyl-3-alkyl-, 4-alkyl-, 5-alkyl- and 6-alkylphenols (isomeric saligenins) are depicted in Scheme 1 (5 and
Scheme 1. Synthesis of anacardic alcohols (2-hydroxymethyl-3-alkylphenols). Reagents: (i) LiAlH4 , THF; HCl.
179
Scheme 2. Synthesis of 2-hydroxymethyl-3-alkylphenols. Reagents: (i) LDA, THF, HMPA, RBr; H3 O+ , (ii) BBr3 , CH2 Cl2 , 78 C, H2 O, (iii) LiAlH4 , THF; HCl.
Scheme 3. Synthesis of 2-hydroxymethyl-4-alkylphenols. Reagents: (a) (i) EtMgBr, Et2 O, HMPA, (CH2 O)n ; HCl, (ii) NaBH4 , MeOH; HCl.(b) (iii), (iv) as in (a), respectively.
Scheme 4. Synthesis of isoanacardic compounds (2-hydroxymethyl-5-alkylphenols). Reagents: (i) (R = R1 = H), CO2 , KOH, ; HCl, (ii) (R1 = H), LiAlH4 , THF; HCl, (iii) EtMgBr, Et2 O, HMPA, (CH2 O)n ; HCl, (iv) NaBH4 , MeOH, 0 C; HCl, (v) NaOH, MeOH, HCHO.
180
Scheme 5. Synthesis of 3-n-alkylphenols, 2-hydroxy-4-n-alkyl-benzaldehydes and 2-hydroxymethyl-5-n-alkylphenols. Reagents: (i) RCH2 P+ (Ph)3 Br , BuLi, THF, (ii) PdC, H2 , EtOH, (iii) EtMgBr, Et2 O, HMPA, (CH2 O)n ; HCl, (iv) NaBH4 , MeOH; HCl.
Scheme 6. Synthesis of 2-hydroxy-3-alkylbenzaldehydes and 2-hydroxymethyl-6-alkylphenols. Reagents: (a) (i) C8 H17 P+ (Ph)3 Br , BuLi, THF, (ii) PdC, H2 , EtOH, (iii) EtMgBr, Et2 O, HMPA, (CH2 O)n ,; HCl, (iv) NaBH4 , MeOH; HCl, (v) Al, , C8 H16 ; aqueous H2 SO4 , (vi) EtMgBr, Et2 O, HMPA, (CH2 O)n ; HCl, (vii) NaBH4 , MeOH; HCl.
6), Scheme 2 (24), Scheme 3 (19 and 21), Scheme 4 (9, R1 = H), Scheme 5 (12) and Scheme 6 (15) (Section 3). To aid structure/property correlation, homologous members of the structurally isomeric saligenins, not available from natural sources, were synthesised to determine the role of chain length and the position of the alkyl chain substituent in the aryl ring on the efciency of the resultant boric acid extractant. The effect of branching in the side chain was studied by a comparison of fossil fuel-derived synthetic compounds having t-butyl, t-octyl and t-nonyl side chains with those in the isomeric n-alkyl series.
2. Experimental procedures 2.1. Materials Cashew nuts, of Indian and Mozambique origin, were obtained from Gill, Duffas and Landauer, London, SE1 and half shells from Mr. M. Grimminger, Buhler Miag, Barnet, London. Technical cashew nutshell liquid was obtained from 3M Research Ltd., St Paul, MN, USA. Japanese lac was obtained with the help of the Japanese Trade Centre, London, from Dr. M. Sato, Industrial Research Laboratory, Sendai,
181
Japan. A. giganteum was made available with the help of Prof. Tereza Pastore, University of Brasilia, Brazil. Chemicals were obtained from Aldrich Chemical Co. other than t-nonylphenol (3,5,5-trimethylhexylphenol) and t-octylphenol, which were both from ICI. 2.2. Chromatography Analytical thin layer chromatography (TLC) was effected with Whatman silica gel 60AMK6F plates (1 in. 3 in.) having a 250 m layer and preparative TLC with Merck silica gel 60GF (20 cm20 cm) with a 1 mm layer. Solvents A to N had the following compositions: A, chloroform:ethyl acetate (95:5); B, chloroform:ethyl acetate:formic acid (95:5:2); C, chloroform:ethyl acetate (90:10); D, dichloromethane:light petroleum (4060 C) (50:50); E, diethyl ether:light petroleum (4060 C) (50:50); F, chloroform:light petroleum (6080 C) (50:50); G, acetone; H, chloroform:ethyl acetate (98:2); I, diethyl ether:light petroleum (4060 C) (40:60); J, chloroform:light petroleum (6080 C) (70:30); K, diethyl ether:light petroleum (4060 C):0.880 ammonia (70:30:4); L, diethyl ether:light petroleum (4060 C):formic acid (70:30:2); M, light petroleum (6080 C):chloroform (70:30); N, light petroleum (6080 C):chloroform (80:20). For synthetic work, diethyl ether and benzene were dried over anhydrous calcium chloride and then overnight over sodium wire. Dry dichloromethane was obtained by reuxing over calcium hydride prior to distillation. THF was dried by reuxing over sodium with benzophenone ketyl radical as indicator. Column chromatography was carried out with BDH silica gel, particle size 0.130.25 mm. For ash chromatography, Merck kieselgel 60 (230400 mesh) was used, and for dry ash chromatography, Merck kieselgel 60H and 60GF. 2.3. Spectroscopy Infrared spectra were recorded on a Perkin Elmer 1420 spectrophotometer. 1 H NMR spectra were determined with Varian T60 (60 mHz) and CFT20 instruments with tetramethylsilane as internal standard. Mass spectra were obtained on a modied AEI MS902 instrument and accurate mass determinations
were made by the SERC Mass Spectrometry Centre at the University College of Wales, Swansea. 2.4. Separations of phenolic lipids 2.4.1. Anacardic acid (1) from natural cashew nut-shell liquid (CNSL), Anacardium occidentale The described method (Tyman et al., 1989) was used with cashew nuts (400.0 g), from which by carbon tetrachloride extraction, natural CNSL (91.08 g, 32.6%) was recovered and thence by lead salt precipitation, ltration and regeneration with cold dilute nitric acid and ethereal extraction, anacardic acid was obtained as a viscous brown liquid (26.68 g, 29.3%). Recoveries varied between 29 and 35%. Rf 0.56 (solvent B); max (lm, cm1 ), 3100, 1220 (OH), 3010, 1610 (C=C), 1660 (C=O), 1380 (CO); H (CFT20, CCl4 ), 0.731.0 (CH3 , unresolved t), 1.171.63 [m, (CH2 )n ], 1.832.20 (CH2 CH=CH, m), 2.63.06 [CH2 Ar, CH2 (CH=CH)2 ], 4.735.30 (CH2 =CH, CH=CH, m), 6.577.43 (HAr, m, 3H), 11.23 (HO, HO2 C, bs, 2H, D2 O exch.); m/z, M+ (%), 348.6 (7.7), 346.6 (53.3), 344.6 (17.6), 342.6 (28.7). 2.4.2. Anagigantic acid (2) (2-hydroxy-6-undecylbenzoic acid) from Anacardium giganteum The shells from the nut were cracked and the phenolic lipids extracted in the same way as described for the cashew. The shell liquid (6.71 g) in methylated spirit (50 cm3 ) was added to lead hydroxide prepared from lead nitrate (3.81 g, 0.012 mol) and sodium hydroxide (0.92 g, 0.023 mol) and the precipitated red/brown solid ltered and washed with methylated spirit (3 100 cm3 ). A suspension in methylated spirit (100 cm3 ) was acidied with cold nitric acid to liberate anagigantic acid which was extracted with diethyl ether. The combined extracts were washed with saturated brine (7 50 cm3 ), dried with magnesium sulphate and the solvent evaporated to give a brown solid (2.45 g, 36.5%) which was crystallised (light petroleum) to afford cream crystals (2.22 g, 90.6%), mp, 75.576.6 C; Rf 0.92 (solvent B); max (KBr disc, cm1 ), 3350, 1220 (OH), 3050, 1310 (OH, carboxylic acid), 1650 (C=O), 1610 (C=C), 1380 (CO); H (CCl4 ), 0.801.57 [(CH2 )9 , Me, m, 21H], 2.703.07 (CH2 Ar, t, 2H, J 8 Hz), 6.507.30 (HAr, 2d superimposed on dd, J 8 and 16 Hz), 10.30 (HOAr and
182
HO2 C, bs, 2H, D2 O exch.); m/z, M+ (%), 292.4 (9.1). C18 H28 O3 requires 292.4, 274.4 (3.9), M+ H2 O. 2.4.3. Cardanol (3) from technical CNSL (Tyman, 1983, 1992; Patel et al., 1981; Tyman et al., 1992) A variety of methods are available and the following is dependent on the more selective hydroxymethylation and subsequent polymerisation of cardol, compared with cardanol. To technical CNSL (250.0 g, 8.33 mol) in methanol (1000 cm3 ) at 45 C, concentrated HCl (20 cm3 ) was added to give pH 1, and then 40% (w/v) methanolic formaldehyde solution (217.6 g, 7.25 mol) dropwise over 1 h. The mixture was stirred and heated at 4550 C for 48 h after which it was cooled, neutralised with 1 M sodium hydroxide and concentrated in vacuo. The residue (305.0 g) in diethyl ether (500 cm3 ) was washed with saturated brine (6 500 cm3 ), dried with magnesium sulphate, ltered and the solvent evaporated in vacuo to give a brown oil (303.65 g), vacuum distillation of which afforded cardanol as a clear yellow oil, bp 190 C/0.1 mmHg (126.69 g, 41.7% of CNSL used), free from cardol; Rf 0.71 (solvent B); argentation TLC (solvent B), 0.97 (15:0), 0.64 (15:1), 0.43 (15:2), 0.20 (15:3); max (lm, cm1 ), 3350, 1170 (OH), 1590 (C=C), 1370 (CO), 700 (1,3-disubstituted ring); H (CCl4 ), 0.731.0 (unresolved t, Me), 1.171.60 [(CH2 )n , m], 1.832.23 (CH2 CH=CH, m), 2.302.90 [CH2 Ar, CH2 (CH=CH)2 ], 4.735.70 (CH2 =CH, CH=CH, m), 6.437.17 (HAr and HOAr, m, 5H, 1H, D2 O exch.); m/z, M+ (%), 304.6 (1.9, 15:0), 302.6 (7.3, 15:1), 300.6 (3.7, 15:2), 298 (4.4, 15:3). 2.4.4. Urushiol (4) (Matthews and Tyman, 1982) Analytical TLC (solvent C) of Japanese lac (10% in chloroform) indicated cardanol (Rf 0.82), urushiol constituents (Rf 0.63, 0.42, 0.29 and 0.27) and polymeric material (Rf 0.11). Column chromatography of Japanese lac (15.00 g) gave the following fractions, eluent, weight: 112, chloroform, 0.84 g; 1348, chloroform:ethyl acetate (90:10), 9.75 g; residue on column, diethyl ether, 4.21 g. Urushiol was obtained from fractions 1348 by dry ash chromatography with light petroleum (6080 C)/chloroform with gradient elution and nally chloroform/ethyl acetate giving 9.15 g (61.0% on urushiol used); Rf 0.57 (solvent C); max (lm,
cm1 ), 3450, 1190, 3000, 1610, 1380; H (CFT20, CDCl3 ), 0.821.00 (Me, unresolved t), 1.162.00 [m, (CH2 )n , CH2 CH=CH], 2.302.83 [m, CH2 Ar and CH2 (CH=CH)2 ], 4.836.16 (m, CH=CH and HAr), 6.33(HOAr, s, 2H, D2 O exch.); m/z, M+ , 320, 318.6 (monoene, 21.7%), 316.5 (diene, 4.8%), 314.6 (triene, 10.1%). 2.4.5. Isoanacardic acid (7, R = n = H) from carboxylated technical CNSL Isoanacardic acid was extracted from carboxylated technical CNSL, prepared as described (Durrani et al., 1980). The reaction product from carboxylation (200.35 g) in methylated spirit (100 cm3 ) was added to lead hydroxide suspended in methylated spirit (100 scm3 ), [prepared from lead nitrate (97.04 g, 0.582 mol) in water (300 cm3 ) and sodium hydroxide (23.44 g, 0.582 mol) in water (150 cm3 )]. The mixture was stirred for 30 min, the red brown solid was ltered, washed with methylated spirit and acidied with cold dilute nitric acid to liberate the product which was extracted with diethyl ether (2 100 cm3 ). The combined extracts were washed with saturated brine (2 200 cm3 ), dried with magnesium sulphate, ltered and evaporated in vacuo to give a viscous brown oil (20.86 g, 10.4%); Rf 0.44 (solvent B), argentation TLC (solvent B), 0.98, saturated, 0.62, monoene, 0.43, diene, 0.26, triene; max (lm, cm1 ), 3150, 13,200, 1220 (OH), 3010, 1625 (C=C), 1660 (C=O), 1390 (CO) (phenol); H (CCl4 ), 0.731.0 (Me, unresolved t), 1.131.50 [(CH2 )n , m], 1.872.23 (CH2 CH=CH, m), 2.402.87 [CH2 Ar and CH2 (CH=CH)2 , m], 4.775.37 (CH2 =CH and CH=CH, m) 6.536.80 (HAr, s superimposed on d, J 8 Hz, 2H), 7.637.87 (HAr, d, J 8 Hz, 1H), 10.2010.63 (HOAr and HO2 C, bs, 2H, D2 O exch.); m/z, M+ (%), 348.6 (6.7), 346.6 (22.1), 344.6 (12.0), 342.6 (143.2). 2.5. Semi-synthetic preparation of 1,3-diols from phenolic lipid sources 2.5.1. Anacardic alcohol (5, n = 0) (2-hydroxymethyl-3-pentadecylphenol) (i) (15:0)-Anacardic acid, prepared by catalytic hydrogenation of (5) as described (Lam and Tyman, 1982) (2.83 g, 0.008 mol) in dry THF (50 cm3 ), was added dropwise to lithium aluminium hydride
183
(1.52 g, 0.04 mol) in dry THF (30 cm3 ) cooled to 0 C under nitrogen, after which the mixture was warmed to 5055 C for 7 h and then left at ambient temperature for 16 h. Excess hydride was decomposed by the addition of ethyl acetate and after the addition of dilute hydrochloric acid, the mixture was extracted with diethyl ether. The combined extracts were washed with saturated brine (5 25 cm3 ) dried (magnesium sulphate), and concentrated in vacuo to yield a brown solid which was recrystallised (light petroleum) to give cream crystals (1.46 g, 53%), mp 6365 C, lit. (Gulati and Subba Rao, 1964), 6566 C; Rf 0.39 (solvent B); max (KBr, cm1 ), 3500, 1000 (primary OH), 3150, 1190 (OH, phenol), 1590 (C=C), 1360, 1260 (CO, phenol and primary OH); H (CDCl3 ), 0.831.53 [(CH2 )13 , Me, 29H], 2.302.80 (CH2 Ar, partially resolved t and s, HOCH2 Ar, 3H, D2 O exch.), 5.03 (ArCH2 OH, s, 2H), 6.807.50 (HAr and HOAr, m, 4H, 1H, D2 O exch.); m/z, M+ (%), 334 (18.5). C22 H38 O2 requires 334.335 (4.4, M+ + 1). (ii) Anacardic alcohol (Mehet, 1988) (5): reduction of anacardic acid Anacardic acid (1) (43.54 g, 0.126 mol) was reduced in THF by the same procedure as for the saturated compound with lithium aluminium hydride (14.32 g, 0.189 mol). The crude product was puried by dry-column ash chromatography with gradient elution to give 5 as a viscous brown oil (33.04 g, 79.1%); Rf 0.38 (solvent B); max (liquid, cm1 ), 3400, 1190, 1060 (OH), 1620 (C=C), 1380 1270 (CO, phenol and primary OH); H (CCl4 ), 0.730.97 (Me, unresolved t), 1.11.50 [(CH2 )n , m]1.772.17 (CH2 CH=CH, m) 2.232.87 (CH2 Ar and CH2 (CH=CH)2 , m), 3.674.0 (HOCH2 Ar, bs, 1H, D2 O exch.), 4.67 (HOCH2 Ar, s, 2H), 4.775.07 (CH2 =CH, m), 5.075.50 (CH=CH, m), 6.176.90 (HAr and HOAr, m, D2 O exch.); m/z, M+ (%), 334.4 (0.9), 332.4 (2.2), 330.4 (1.2), 328.4 (0.8). In a similar way natural CNSL (11.00 g) containing anacardic acid (80%), cardol (15%) and 2methylcardol/cardanol (5%) was reduced with LiAlH4 (3.64 g, 0.096 mol) in THF and worked up as before to give a viscous brown oil (9.45 g, 85.9% recovered); Rf (solvent B) 0.74 (cardanol), 0.66 (anacardic acid,
traces), anacardic alcohol (0.45), and cardol (0.39); m/z, M+ (%), 334.3 (0.7), 332.3 (1.1), 330.4 (0.9), 328.4 (0.7). 2.5.2. Methyl 2-hydroxy-4-pentadecylbenzoate (7,n = 0, R = Me, R1 = H) (i) Diazomethane was generated by adding diazald (4.3 g, 0.02 mol) in diethyl ether (50 cm3 ) to potassium hydroxide (1.38 g, 0.025 mol) in water (2 cm3 ) and ethanol (5 cm3 ) at 65 C and collected in diethyl ether (20 cm3 ) at 0 C. This solution of diazomethane (0.6 g, 0.014 mol) in diethyl ether was then added to isoanacardic acid (1.38 g, 0.004 mol) in diethyl ether, until the solution was pale yellow and nitrogen evolution had ceased. Concentration of the mixture and crystallisation of the residue from light petroleum gave cream needles (1.34 g, 93.1%), mp 4546.5 C; Rf 0.73 (solvent F). Found, C, 76.16; H, 10.44. C23 H38 O3 requires C, 76.20; H, 10.57%; max (KBr, cm1 ), 3180, 1220 (OH), 1680 (C=O), 1620 (C=C), 1340, 1250 (CO); H (CDCl3 ), 0.801.52 [(CH2 )13 , Me, m, 26H], 2.402.70 (CH2 Ar, t, J 7 Hz, 2H), 3.90 (MeO2 CAr, s, 3H), 6.606.70 (HAr, d, J 8 Hz, 1H), 7.21 (HAr, s, 1H), 7.627.72 (HAr, d, J 8 Hz, 1H), 10.62 (HOAr, s, 1H, D2 O exch.); m/z, M+ (%), 362.4 (100), M+ + 1, 363.5 (27.2). (ii) A mixture of isoanacardic acid (1.82 g, 0.005 mol) in benzene (20 cm3 ) containing anhydrous potassium carbonate (3.42 g, 0.025 mol) and dimethyl sulphate (2.4 cm3 , 0.025 mol) was reuxed for 24 h. The cooled mixture was ltered and the ltrate was washed with warm water (5 25 cm3 ) to remove dimethyl sulphate, dried (magnesium sulphate) and the solvent evaporated to give a cream solid which was recrystallised (light petroleum) to afford cream crystals (0.99 g, 52.4%), mp 4243.5 C, identical spectroscopically with the product from method (a). 2.5.3. Methyl 2-methoxy-4-pentadecylbenzoate (7, n = 0, R = R1 = Me) A mixture of isoanacardic acid (0.98 g, 0.003 mol), 3 M sodium hydroxide (4.6 cm3 ), dimethyl sulphate (4.8 cm3 , 0.006 mol), 40% aqueous tetrabutylammonoum hydroxide (0.5 cm3 ) in water (20 cm3 ) and
184
dichloromethane (20 cm3 ) was vibromixed for 3 h when TLC (solvent M) indicated dimethylation was complete. The lower organic layer was separated and washed with warm water (6 50 cm3 ), dried and concentrated to give a cream solid which was crystallised (light petroleum) to afford cream crystals (0.62 g, 58.5%), mp 2931 C; Rf 0.39 (solvent F). Found, C, 76.35; H, 10.89. C24 H40 O3 requires C, 76.55; H, 10.71%; max (KBr, cm1 ), 1690 (C=O), 1600 (C=C), 1400, 1250, 1240 (CO); H (CCl4 ), 0.671.23 [(CH2 )13 , Me, m, 29H], 2.272.5 (CH2 Ar, t, J 7 Hz, 2H), 3.62 (MeO2 CAr, s, 3H), 3.67 (MeOAr, s, 3H), 6.706.67 (HAr, s on d, J 8 Hz, 2H), 7.437.60 (HAr, d, J 8 Hz, 1H); m/z, M+ (%), 376.4 (100), M+ + 1 377.4 (24.3), M+ OMe, 345.3 (1.3). 2.5.4. 2-Methoxy-4-pentadecylbenzoic acid (7, n = 0, R = H, R1 = Me) Methyl 2-methoxy-4-pentadecylbenzoate (0.50 g, 0.001 mol) in ethanol (10 cm3 ) was reuxed with 1 M ethanolic KOH (3 cm3 ) for 1 h. The cooled mixture was then acidied with dilute hydrochloric acid and the solid product collected, dried and crystallised (light petroleum) to give white needles (0.45 g, 93.8%), mp 80.581.5 C; Rf 0.24 (solvent C). Found, C, 76.38; H, 10.45. C23 H38 O3 requires C, 76.20; H, 10.57%; max (KBr, cm1 ), 3230, 1340 (OH), 1720 (C=O), 1610 (C=C), 1260 (CO); H (CCl4 ), 0.731.50 [(CH2 )13 , Me, m, 29H], 2.472.87 (CH2 Ar, t, J 7 Hz, 2H), 4.03 (MeO, s, 3H), 6.736.97 (HAr, s on d, J 8 Hz, 2H), 7.678.43 (bs, s on d, J 8 Hz, 2H, 1H, D2 O exch.); m/z, M+ (%), 363.2 (81.4). 2.5.5. 2-Hydroxymethyl-5-pentadecylphenyl methyl ether (9, n = 0, R1 = Me) 2-Methoxy-4-pentadecylbenzoic acid (0.36 g, 0.001 mol) and lithium aluminium hydride (0.11 g, 0.001 mol) in the same way as for other reductions, gave the product as cream needles (0.03 g, 85.7%), mp 66.568 C; Rf 0.66 (solvent C). Found, C, 79.46; H, 11.58. C23 H40 O2 requires C, 79.25; H, 11.57%; max (KBr, cm1 ), 3340, 1050 (OH), 1520 (C=O), 1270 (ArOMe), 1260 (CO); H (CCl4 ) 0.831.40 [(CH2 )n , Me, m, 29H], 2.02.67 (CH2 Ar, HOCH2 Ar, t on bs, 3H, 1H, D2 O exch.), 3.80 (MeO, s, 3H), 4.47 (HOCH2 Ar, s, 2H), 6.506.70 (HAr, s on d, J 8 Hz, 2H), 7.07.20 (HAr, d, J 8 Hz, 1H); m/z, M+ (%), 348.4 (100), M+ + 1 349.6 (25.5).
Reduction of methyl 2-methoxy-4-pentadecylbenzoate (0.80 g, 0.002 mol) with lithium aluminium hydride (0.23 g, 0.006 mol) similarly gave the same product, as cream needles, mp 66.567.5 C, Rf 0.66 (solvent C) with similar spectroscopic data as for the product from reduction of the acid. 2.5.6. Isoanacardic alcohol (9, n = 0, R = H) (2-hydroxymethyl-5-pentadecylphenol) (i) By hydride reduction: 2-Hydroxy-4-pentadecylbenzoic acid (1.00 g, 0.001 mol) in THF (20 cm3 ) was added dropwise under nitrogen to a suspension of lithium aluminium hydride (0.34 g, 0.009 mol) in THF (10 cm3 ) cooled to 0 C. After the mixture had been reuxed for 2 h and then allowed to stand for 16 h, ethyl acetate (0.50 cm3 ) was added, followed by dilute hydrochloric acid. Ethereal extraction, washing of the combined extracts with saturated brine, drying (magnesium sulphate) and evaporation afforded a cream solid which was recrystallised (light petroleum) to give pale cream crystals (0.56 g, 75.2%), mp 9697 C; Rf 0.37 (solvent C); max (KBr, cm1 ), 3450, 1000 (OH, primary), 3180, 1220 (OH, phenol), 1630 (C=C), 1380, 1290 (CO); H (CDCl3 ), 0.901.50 [(CH2 )13 , Me, m, 29H], 2.17 (HOCH2 Ar, s, 1H), 2.432.77 (CH2 Ar, t, J 7 Hz, 2H), 4.93 (ArCH2 OH, s, 2H), 6.737.23 (HAr, HOAr, m, 4H, 1H, D2 O exch.); m/z, M+ (%), 334.6 (34.9). C22 H38 O2 requires 334.5, M+ + 1 335.6 (8.4). (ii) This compound was also prepared by reduction of the methyl ester. 2.5.7. Isoanacardic alcohol (9, R = H) (reduction of unsaturated methyl isoanacardate) (i) By hydride reduction: Unsaturated 2-hydroxy4-pentadecylbenzoic acid (4.00 g, 0.012 mol), was methylated with diazomethane (0.50 g, 0.012 mol) in ethereal solution and the methyl ester obtained as a viscous brown oil (3.50 g, 84.1%); Rf 0.35 (solvent N); max (liquid, cm1 ), 3400, 1220 (OH), 3010, 1620 (C=C), 1670 (C=O), 1350 (CO); H (CCl4 ) 0.831.03 (unresolved t, Me) 1.131.57 [(CH2 )n , m], 1.772.27 (CH2 CH=CH), 2.602.97 [CH2 Ar, CH2 (CH=CH)2 , m], 3.93 (MeO, s, 3H),
185
4.775.57 (CH2 =CH, CH=CH, m), 6.477.30 (HAr, m, 3H), 10.93 (HOAr, s, D2 O exch.); m/z, M+ (%), 362.3 (2.1), 360.2 (14.9), 358.2 (4.0), 356.2 (4.0). Methyl isoanacardate (3.14 g, 0.009 mol) in dry THF (60 cm3 ) was added dropwise, under nitrogen, to stirred lithium aluminium hydride (1.05 g, 0.027 mol) in dry THF (30 cm3 ) cooled to 0 C. After reuxing for 2 h, the mixture was worked up as for the saturated compound and puried by chromatography on a silica column with light petroleum (6080 C)/chloroform/ethyl acetate (gradient elution) to give a brown oil (2.56 g, 88.6%); Rf 0.38 (solvent B); max (liquid, cm1 ), 3350, 1190, 1050 (OH), 1620 (C=C), 1390, 1280 (CO); H (CCl4 ) 0.731.03 (unresolved t, Me), 1.171.60 [(CH2 )n , m], 1.802.20 (CH2 CH=CH, m), 2.302.90 [CH2 Ar, CH2 (CH=CH)2 , m], 3.574.20 (HOCH2 Ar, s, 1H, D2 O exch.), 4.67 (HOCH2 Ar, s, 2H), 4.775.13 (CH2 =CH, m), 5.135.53 (CH=CH, m), 6.437.06 (HAr, m, 3H), 7.308.10 (HOAr, s, 1H, D2 O exch.); m/z, M+ (%), 334.2 (1.1), 332.2 (2.8), 330.2 (1.6), 328 (0.9). (ii) By hydroxymethylation: To cardanol (3.04 g, 10 mmol) in methanol (10 cm3 ) sodium hydroxide (0.4 g, 10 mmol) in water (15 cm3 ) was added, followed by 37% aqueous formaldehyde (0.85 g, 10.5 mmol). After reuxing for 4 h, the mixture was cooled, diethyl ether (50 cm3 ) was added and the solution was acidied with 3 M hydrochloric acid. The ethereal solution was washed with saturated brine, dried with magnesium sulphate, ltered and concentrated in vacuo to give a golden oil (3.36 g). The crude product (0.85 g) was puried by preparative TLC (solvent C) to give ve bands (1) Rf 0.64, 0.36 g (42%), cardanol, (2) Rf 0.27, 0.32 g (37.6%, conversion on cardanol used, 71.2%), 2-hydroxymethyl-5-mixed unsaturated pentadecylphenol, unsaturated isoanacardic alcohol, (3) Rf 0.15, 0.03 g (6.7%), which appears to be 4-hydroxymethyl-5-mixed unsaturated pentadecylphenol, (4) Rf 0.03, 0.06 g (12.2%), from spectroscopy, 2,4-dihydroxymethyl-5-mixed unsaturated pentadecylphenol, m/z, 362.5, (5) baseline, probably polymer; for (band 2): max (lm, cm1 ), 3350, 1190, 1020 (OH), 1620 (C=C),
1370, 1270 (CO, phenol and primary OH); max (CDCl3 ), 0.760.94 (Me, t), 1.171.36 [(CH2 )n , m], 1.572.04 (CH2 CH=CH, m), 2.492.56 (CH2 Ar, t, J 7 Hz, 2H), 2.602.78 [CH2 (CH=CH)2 , m], 4.78 (HOCH2 Ar, s, 2H), 4.895.42 (CH2 =CH, CH=CH, m), 6.646.69 (HAr, s on d, 2H), 6.906.94 (HAr, d, J 8 Hz, 1H); m/z, M+ (%), 332.6 (1.6), M+ H2 O, 316.5 (2.4), 314.5 (10.1), 312.5 (7.7), 310.5 (7.2). (iii) By formylation of cardanol (Tyman, 1981) to 8: Ethyl magnesium bromide prepared from bromoethane (3.8 cm3 , 0.05 mol), in dry diethyl ether (30 cm3 ) and magnesium turnings (1.44 g, 0.06 mol), in dry ether (20 cm3 ) was added to a stirred solution of cardanol (15.35 g, 0.051 mol) in dry ether (100 cm3 ) at ambient temperature. After completion of evolution of ethane during 16 h, and distillation of the ether, dry benzene was added, followed by paraformaldehyde (5.98 g, 0.13 mol) and hexamethylphosphoramide (8.8 cm3 , 0.051 mol). The mixture was stirred and reuxed for 6 h with monitoring by TLC (solvent E). After cooling and acidication with dilute sulphuric acid, the mixture was extracted with diethyl ether (200 cm3 ), the ethereal extract was washed with saturated brine (5 150 cm3 ), dried with magnesium sulphate, ltered and concentrated to afford an oil which was puried by column chromatography (light petroleum, 4060 C/diethyl ether, gradient elution) to give a golden oil (14.58 g, 86.9%), 2-hydroxy-4-unsaturated pentadecylbenzaldehyde; Rf 0.69 (solvent E); max (lm, cm1 ), 3200, 1200 (OH), 1660 (C=O), 1520 (C=C), 1380 (CO); H (CCl4 ), 0.731.0 (Me, t), 1.091.47[(CH2 )n m], 1.72.17 (CH2 CH=CH, m), 2.372.80 [CH2 Ar and CH2 (CH=CH)2 , m], 4.675.03 (CH2 =CH, m), 5.065.37 (CH=CH, m), 6.506.70 (HAr, s on d, J 8 Hz, 2H), 7.107.30 (HAr, d, J 8 Hz, 1H), 9.97 (ArCHO, s, 1H), 10.77 (HOAr, s, D2 O exch.); m/z, M+ (%), 332.4 (6.8), 330.4 (29.1), 328.4 (16.8), 326.4 (18.0). Attempts to purify the aldehyde by vacuum distillation rather than chromatographically were not successful due to polymerisation. (iv) Borohydride reduction: The aldehyde (10.01 g, 0.03 mol) in methanol (100 cm3 ) was cooled to 0 C and then treated with sodium borohydride
186
(2.30 g, 0.06 mol) in small portions while the temperature was maintained at 0 C. The mixture was allowed to warm to ambient temperature over 16 h, monitored by TLC (solvent E) and upon completion of reduction, extracted with diethyl ether (200 cm3 ). The ethereal extract was washed with dilute sulphuric acid (4150 cm3 ), then with saturated brine (5 150 cm3 ), dried with magnesium sulphate, ltered and concentrated to give an oil which was puried by dry-column ash chromatography (chloroform/ethyl acetate with gradient elution) to afford a waxy solid (8.31 g, 82.5%); Rf 0.37 (solvent B), identical chromatographically and spectroscopically with the product of methylolation and hydride reduction. 2.5.8. 2-Hydroxymethyl-3-undecylphenol (6) Anagigantic acid (0.92 g, 0.003 mol) in THF was reduced by addition to lithium aluminium hydride (0.35 g, 0.009 mol) in THF as with the previous reductions. The reaction mixture was worked up as before and the crude product crystallised (light petroleum) to give 2-hydroxymethyl-3-undecylphenol as cream crystals (0.48 g, 55.2%), mp 50.351.5 C; Rf 0.28 (solvent B); max (KBr, cm1 ), 3500, 1000 (OH, primary OH), 3180, 1210 (OH, phenol), 1620 (C=C), 1380, 1260 (CO); H (CDCl3 ), 0.761.47 [(CH2 )n , Me, m, 21H], 2.673.06 (CH2 Ar, HOCH2 Ar, s and t, 1H, D2 O exch.), 4.82 (HOCH2 Ar, s, 2H), 6.507.40 (HAr and HOAr, m, 4H, 1H, D2 O exch.); m/z, M+ (%), 278.1 (62.0). C18 H30 O2 requires 278.4, M+ + 1 279.1 (10.1). 2.6. Synthesis of 1,3-diols from homologous 3-alkylphenols by formylation and reduction of 2-hydroxy-4-alkylbenzaldehydes 2.6.1. Synthesis of 3-alkylphenols This range of compounds was synthesised by the Wittig reaction (Maercker, 1965) of 3-hydroxybenzaldehyde and the appropriate alkylidenetriphenylphosphoran, generated from the phosphonium salt with butyllithium, to give the corresponding unsaturated phenol which was hydrogenated to the required 3alkylphenol. Formylation followed by sodium borohydride reduction afforded the 1,3-diol in the series of homologous 2-hydroxymethyl-4-alkylphenols.
The alkyltriphenylphosphonium bromide was prepared by reuxing the 1-bromoalkane (0.50 mol) and triphenylphosphine (0.50 mol) in o-xylene (200 cm3 ) with monitoring by TLC (solvent G). Upon completion of reaction the solvent was decanted from the cooled mixture and the product was washed with 6080 C light petroleum (2 200 cm3 ) and the solvent removed in vacuo to yield the salt as a viscous oil. The stirred phosphonium salt (0.20 mol) in dry THF (200 cm3 ) under nitrogen was treated with a hexane solution of butyllithium (0.20 mol). 3-Hydroxybenzaldehyde (0.20 mol) in dry THF (250 cm3 ) was then added to the phosphoran over 30 min. The reaction mixture changed in colour from wine-red to yellow and after removal of the solvent in vacuo, the residual dark yellow viscous oil in ethereal solution was washed with aqueous sodium metabisulphite (2 200 cm3 ) to remove residual aldehyde. The ethereal solution was dried (magnesium sulphate), ltered, concentrated and the crude product puried by dry-column ash chromatography (chloroform/ethyl acetate with gradient elution) to remove triphenylphosphine oxide. The 1-(3-hydroxyphenyl)alk-1ene (0.06 mol) in ethanol (200 cm3 ) was hydrogenated in the presence of 5% palladium on charcoal (25% of the weight of alkene) at ambient pressure and temperature with TLC monitoring (solvent H). Removal of the catalyst by ltration and evaporation of the solvent in vacuo left the required 3-n-alkylphenol. 2.6.2. 3-n-butylphenol (10, R1 = n-Bu) 1-Bromopropane (34.81 g, 0.28 mol) and triphenylphosphine (74.24 g, 0.28 mol) formed n-propyltriphenylphosphonium bromide (104.20 g, 95.6%) which in THF was treated with a hexane solution of n-butyllithium (230 cm3 , 0.27 mol) and then with 3hydroxybenzaldehyde (33.06 g, 0.27 mol) in THF. The puried product, 1-(3-hydroxyphenyl)but-1-ene (17.9, 44.7%), was obtained as a yellow oil; Rf 0.80 (solvent H); max (lm, cm1 ), 3200 (OH), 1590 (C=C), 1300, 970 (CH=CH); max 1-(3-hydroxyphenyl)but-1-ene (6.70 g, 0.045 mol) was hydrogenated in the presence of 5% PdC (1.70 g) to give a light brown oil (6.47 g, 95.8%) which showed a single band, Rf 0.81 (solvent H, argentation TLC); max (lm, cm1 ), 3300, 1180 (OH), 28502950 (CH), 1590 (C=C), 1490 (CH2 def.); H (CDCl3 ), 0.671.73 [(CH2 )2 , Me, m, 7H], 2.302.67 (CH2 Ar, t, J 7 Hz, 2H), 6.408.20 (HAr
187
and HOAr, m, with bs, 5H, 1H, D2 O exch.); m/z, M+ (%), 150.1 (29.3), M+ + 1, 151.1 (3.1), M+ CHEt, 108.1 (100), M+ required for C10 H14 O, 150.2. 2.6.3. 3-n-Octylphenol (10, R1 = C8 H17 ) 1-Bromoheptane (21.48 g, 0.12 mol) and triphenylphosphine (31.44 g, 0.12 mol) formed the phosphonium salt heptyltriphenylphosphonium bromide (47.25 g, 89.3%). The salt (46.60 g, 0.10 mol) with n-butyllithium (74.44 cm3 , 0.10 mol) and 3hydroxybenzaldehyde (12.00 g, 0.10 mol), reacted by the general method, afforded, after purication by dry-column ash chromatography, 1-(3hydroxyphenyl)oct-1-ene as a yellow oil (11.27 g, 52.3%) showing a single band, Rf 0.59 (solvent H). Hydrogenation of 1-(3-hydroxyphenyl)oct-1-ene (19.00 g, 0.09 mol) in the presence of 5% PdC (4.75 g) gave 3-n-octylphenol, as a golden oil (8.26 g, 43.0%) showing one band by TLC, Rf 0.72 (solvent H, argentation TLC); max (lm, cm1 ), 3350, 1180 (OH), 28502950 (CH), 1590 (C=C), 1480 (CH2 def.); H (CDCl3 ), 0.671.73 [(CH2 )6 , Me, m, 15H], 2.50 (CH2 Ar, t, J 7 Hz, 2H), 5.57 (HOAr, bs, 1H, D2 O exch.), 6.437.20 (HAr, m, 4H); m/z, M+ (%), 206.1 (55.7). Required for C14 H22 O, 206.3, M+ + 1, 207.1 (8.9), M+ C4 H9 , 149.1 (9.5), M+ C7 H14 , 108.1 (70.2), M+ C7 H15 , 107.1 (18.1). 2.6.4. 3-n-Nonylphenol (10, R1 = C9 H19 ) By the general procedure, 1-bromooctane (100.0 g, 0.518 mol) and triphenylphosphine (135.72 g, 0.518 mol) gave the phosphonium salt, n-octyltriphenylphosphonium bromide (208.0 g, 88.25%). The salt (90.0 g, 0.198 mol), n-butyllithium (132 cm3 , 0.198 mol) and 3-hydroxybenzaldehyde (24.16 g, 0.198 mol), by the general method with nal purication by dry-column ash chromatography, gave 1(3-hydroxyphenyl)non-1-ene as a golden oil (20.36 g, 47.2%) having a single band by TLC, Rf 0.71 (solvent A). 1-(3-Hydroxyphenyl)non-1-ene (14.40 g, 0.066 mol) was hydrogenated in the presence of 5% PdC (3.63 g) to afford a golden oil (11.56 g, 79.0%) showing a single band, Rf 0.71 (solvent A, argentation TLC); max (lm, cm1 ), 3200, 1170 (OH), 28502990 (CH), 1590 (C=C), 1470 (CH2 def.); H (CCl4 ), 0.671.73 [(CH2 )7 , Me, m, 17H], 2.232.63 (CH2 Ar, t, J 7 Hz, 2H), 6.308.30 (HAr and HOAr, m and bs, 5H, 1H,
D2 O exch.); m/z, M+ (%), 220.4 (11.1). Required for C15 H24 O, 220.3, M+ + 1, 221.4 (1.7), M+ C7 H15 , 121.2 (8.6), M+ C8 H16 , 108.2 (100), M+ C8 H17 , 107.2 (29.5). 2.6.5. 3-n-Undecylphenol (10, R1 = C11 H23 ) By the general method, 1-bromodecane (60.00 g, 0.27 mol) with triphenylphosphine (71.26 g, 0.27 mol) formed the salt, n-decyltriphenylphosphonium bromide (114.90 g, 87.5%). The salt (100.00 g, 0.21 mol), n-butyllithium (138 cm3 , 0.21 mol) and 3-hydroxybenzaldehyde (25.01 g, 0.21 mol) afforded 1-(3-hydroxyphenyl)undec-1-ene, puried as with the other compounds to give a golden oil (18.50 g, 36.7%) showing a single band by TLC, Rf 0.57 (solvent A). 1-(3-Hydroxyphenyl)undec-1-ene (17.03 g, 0.07 mol) was hydrogenated in the presence of 5% PdC (4.25 g) to give 3-n-undecylphenol as a yellow oil (10.95 g, 63.8%) having a single band by argentation TLC, Rf 0.58 (solvent A); max (lm, cm1 ), 3350, 1160 (OH), 28702980 (CH ), 1600 (C=C), 1490 (CH2 def.), 1380 (CO); H (CDCl3 ), 0.671.67 [(CH2 )9 , Me, m, 21H], 2.332.67 (CH2 Ar, t, J 7 Hz, 2H), 6.507.90 (HAr and HOAr, m, 5H, 1H, D2 O exch.); m/z, M+ (%), 248.3 (5.5). Required for C17 H28 O, 248.4, M+ + 1, 249.3 (1.0), M+ C9 H19 121.1 (9.1), M+ C10 H20 , 108.1 (100), M+ C10 H21 , 107.1 (32.3). 2.7. Synthesis of 2-hydroxy-, 3-alkyl-, 4-alkyl- and 5-alkylbenzaldehydes by formylation of 2-, 3-, and 4-alkylphenols, respectively In a general method, ethyl magnesium bromide prepared from bromoethane (0.01 mol) in dry diethyl ether (10 cm3 ) and magnesium turnings (0.015 mol) in diethyl ether (10 cm3 ) was added to a stirred solution of the alkylphenol (0.01 mol) in diethyl ether (20 cm3 ) and the mixture reacted at ambient temperature for 16 h. After removal of the ether, dry benzene (50 cm3 ) was added to the phenoxymagnesium bromide, then paraformaldehyde (0.025 mol) followed by hexamethylphosphoramide, HMPA (0.01 mol). The resulting mixture was reuxed for 46 h with monitoring by TLC (solvent E). The mixture was cooled, acidied with dilute sulphuric acid, extracted with diethyl ether
188
(100 cm3 ), and the combined extracts washed with saturated brine (4 100 cm3 ), dried with magnesium sulphate, and evaporated in vacuo to give the product which was puried by column chromatography. By this methodology, aldehydes were synthesised from 2-n-nonylphenol, 3-n-butylphenol, 3-tbutylphenol, 2-(1,1,3,3-tetramethylbutyl)phenol, 3n-nonylphenol, 3-n-undecylphenol, 4-t-butylphenol, 4-(1,1,3,3-tetramethylbutyl)phenol, 4-n-nonylphenol, 4-(3,5,5-trimethylhexyl)phenol and 2-chloro-4-(1,1,3, 3-tetramethylbutyl)phenol. 2.7.1. 2-Hydroxy-4-alkylbenzaldehydes 2.7.1.1. 2-Hydroxy-4-n-butylbenzaldehyde (11, R1 = n-Bu). 3-n-Butylphenoxymagnesium bromide was prepared by the general method from bromoethane (1.5 cm3 , 0.02 mol) magnesium turnings (0.60 g, 0.025 mol), and 3-n-butylphenol (3.00 g, 0.02 mol). Paraformaldehyde (2.30 g, 0.05 mol) and HMPA (3.5 cm3 ) were added and reaction afforded the product which was puried by column chromatography on silica gel G (6080 C light petroleum/diethyl ether with gradient elution to give a yellow oil (1.81 g, 50.8%); Rf 0.65 (solvent E); max (lm, cm1 ), 3200, 1180 (OH), 1690 (C=O), 1590 (C=C), 1380 (C=O); H (CCl4 ) 0.701.76 [(CH2 )2 , Me, m, 7H], 2.402.70 (CH2 Ar, t, J 7 Hz, 2H), 6.537.40 (HAr, m, 3H), 9.70 (CHO, s, 1H), HOAr, s, 1H, D2 O exch.); m/z, M+ (%), 178.4 (39.7), M+ + 1, 179.4 (5.4). M+ , required for C11 H14 O2 , 178.2. 2.7.2. 2-Hydroxy-4-t-butylbenzaldehyde (11, R1 = t-Bu) 3-t-Butylphenoxymagnesium bromide was prepared from bromoethane (5.3 cm3 , 0.07 mol), magnesium turnings (1.80 g, 0.075 mol) and 3-t-butylphenol (10.00 g, 0.07 mol). Formylation was effected with paraformaldehyde (7.71 g, 0.175 mol) and HMPA (11.7 cm3 , 0.07 mol) and the crude product was puried as before to afford a yellow oil (9.34 g, 78.7%); Rf 0.66 (solvent E); max (lm, cm1 ), 3200, 1190 (OH), 1690 (C=O), 1620 (C=C), 1380 (CO); H (CCl4 ) 1.26 (Me3 C, s, 9H), 6.777.33 (HAr, m, 3H), 9.67 (CHO, s, 1H), 10.77 (HOAr, s, 1H, D2 O exch.); m/z, M+ (%), 178.5 (49.3). Calculated for C11 H14 O2 , 178.2.
2.7.3. 2-Hydroxy-4-n-octylbenzaldehyde (11, R1 = C8 H17 ) 3-n-Octylphenoxymagnesium bromide was prepared from bromoethane (1.0 cm3 , 0.014 mol), magnesium turnings (0.46 g, 0.019 mol) and 3-n-octylphenol. The addition and reaction with paraformaldehyde (1.61 g, 0.035 mol) in the presence of HMPA (2.3 cm3 , 0.014 mol) gave the product which was puried as before to give a yellow oil (1.79 g, 53.6%); Rf 0.69 (solvent E); max (lm, cm1 ), 3250, 1210 (OH), 1690 (C=O), 1590 (C=C), 1380 (CO); H (CDCl3 ), 0.721.47 [(CH2 )6 , Me, m, 15H], 2.402.73 (CH2 Ar, t, J 7 Hz, 2H), 6.607.40 (HAr, m, 3H), 9.63 (CHO, s, 1H), 10.83 (HOAr, s, 1H, D2 O exch.); m/z, M+ (%), 234.3 (7.4), M+ + 1, 235.3 (1.3). Required for C15 H22 O2 234.3. 2.7.4. 2-Hydroxy-4-n-nonylbenzaldehyde (11, R1 = C9 H19 ) 3-n-Nonylphenoxymagnesiumbromide obtained from bromoethane (0.37 cm3 , 0.005 mol) magnesium turnings (0.24 g, 0.01 mol) and 3-nonylphenol (1.00 g, 0.005 mol) was treated with paraformaldehyde (0.58 g, 0.013 mol) and HMPA (0.90 cm3 , 0.005 mol) and reacted to afford the crude product which was puried by dry-column ash chromatography (4060 C, light petroleum/diethyl ether, with gradient elution), to give a yellow oil (0.61 g, 54.0%); Rf 0.72 (solvent E); max (lm, cm1 ), 3300, 1220 (OH), 1680 (C=O), 1580 (C=C), 1390 (CO); H (CCl4 ), 0.731.47 [(CH2 )7 , Me, m, 17H], 2.32.63 (CH2 Ar, t, J 7 Hz, 2H), 6.577.17 (HAr, m, 3H), 9.57 (CHU, s, 1H), 10.47 (OH, s, D2 O exch.); m/z, M+ (%), 248.4 (30.9), M+ + 1 (249.4 (3.5). Required for C16 H24 O2 , 248.4. 2.7.5. 2-Hydroxy-4-n-undecylbenzaldehyde (11, R1 = C11 H23 ) 3-n-Undecyl phenoxy magnesium bromide was prepared from bromoethane (1.0 cm3 , 0.014 mol) magnesium turnings (0.46 g, 0.019 mol) and 3-nundecylphenol (3.50 g, 0.014 mol). Treatment with paraformaldehyde (1.61 g, 0.035 mol) and HMPA (2.3 g, 0.014 mol) gave, upon reaction, the crude product which was recrystallised from light petroleum, to give cream needles (2.05 g, 52.7%); Rf 0.74 (solvent E); max (lm, cm1 ), 3300, 1210 (OH), 1690 (C=O), 1590 (C=C), 1390 (CO); H (CCl4 ), 0.831.37 [(CH2 )9 , Me, m, 21H], 2.57 (CH2 Ar, t, J 7 Hz,
189
2H), 6.677.47 (HAr, m, 3H), 9.83 (CHO, s, 1H), 10.93 (HO, s, 1H, D2 O exch.); m/z, M+ (%), 276.0 (11.1), M+ + 1 277.0 (3.6). Required for C18 H28 O2 , 276.2. 2.8. 2-Alkylphenols 2.8.1. 2-n-Nonylphenol (13) In the same way as for 3-alkylphenols, 2-nonylphenol was synthesised by the Wittig reaction. 1-Bromooctane (50.00 g, 0.259 mol) and triphenylphosphine (67.86 g, 0.259 mol) formed n-octyltriphenylphosphonium bromide (116.32 g, 98.7%). The salt (75.00 g, 0.165 moll), n-butyllithium (103.2 cm3 , 0.165 mol), and 2-hydroxybenzaldehyde (20.13 g, 0.165 mol) were reacted to give, after purication by dry-column ash chromatography (6080 C, light petroleum/chloroform and gradient elution), a yellow oil, 1-(2-hydroxyphenyl)non-1-ene (20.45 g, 56.8%); Rf 0.88 (solvent A). 1-(2-Hydroxyphenyl)non-1-ene (20.00 g, 0.092 mol) was hydrogenated in the presence of 10% PdC (2.50 g) to afford a yellow oil, 2-n-nonylphenol, showing, after purication, a single band (16.26 g, 80.6%); Rf 0.55 (solvent A, argentation TLC); max (lm, cm1 ), 3400, 1170 (OH), 28502990 (CH), 1600 (C=C), 1470 (CH2 def.), 1370 (CO); H (CDCl3 ) 0.701.50 [(CH2 )7 , Me, m, 17H], 1.772.27 (CH2 Ar, t, J 7 Hz, 2H), 6.307.93 (HAr and HOAr, m, 5H, 1H, D2 O exch.); m/z, M+ (%), 220.4 (11.6). Required for C15 H24 O, 220.3, M+ + 1, 211.4 (7.6). 2.8.2. 2-(1,1,3,3-Tetramethylbutyl)phenol (Laan and Ward, 1987) (16) To melted phenol (104.45 g, 1.11 mol) at 41 C, aluminium turnings (1.04 g, 1%) were added. Hydrogen evolution occurred and a rise in temperature to 165 C after which the mixture was cooled to 100 C and treated with 2,4,4-trimethylpent-1-ene (99.86 g, 0.89 mol). The colour changed to red-brown and the temperature was maintained at 100110 C during TLC monitoring. After no further change the cooled mixture was diluted with water (50 cm3 ) and extracted with chloroform (100 cm3 ). The extract was washed with dilute sulphuric acid (3 50 cm3 ), then with dilute NaOH (3 50 cm3 ), dried, ltered and concentrated in vacuo to give a viscous yellow oil, bp
88100 C/1.0 mmHg, which was crystallised (light petroleum) to afford white platelets, mp 3840 C (50.98 g, 27.7%); Rf 0.63 (solvent E); max (KBr disc, cm1 ), 3540, 1190 (OH, phenol), 1610 (C=C), 1370 (CO), 760 (CH, 1,2-disubstituted ring); H (CDCl3 ), 0.77 (Me3 CH2 , s, 9H), 1.43 (Me2 CAr, s, 6H), 1.90 (CH2 CMe2 , s, 2H), 4.67 (HOAr, s, 1H, D2 O exch.), 6.277.17 (HAr, m, 4H); m/z, M+ (%) 206.3 (7.6), M+ + 1 207.3, 1.1). Calculated for C14 H22 O, 206.1670. Found, 206.1669. 2.9. 2-Hydroxy-3-alkylbenzaldehydes 2.9.1. 2-Hydroxy-3-n-nonylbenzaldehyde (14) 2-n-Nonylphenoxy magnesium bromide was prepared from bromoethane (1.3 cm3 , 0.017 mol), magnesium turnings (0.53 g, 0.022 mol), and 2-nnonylphenol (3.80 g, 0.017 mol) and formylated by reaction with paraformaldehyde (1.95 g, 0.0425 mol) and HMPA (2.80 cm3 , 0.017 mol) to give the product which was puried by dry-column ash chromatography (4060 C, light petroleum/diethyl ether with gradient elution), to give a yellow oil (1.80 g, 42.0%); Rf 0.68 (solvent E); max (lm, cm1 ), 3200, 1220 (OH), 1690 (C=O), 1590 (C=C), 1390 (CO); H (CCl4 ), 0.671.53 [(CH2 )7 , Me, m, 17H], 1.932.27 (CH2 Ar, t, J 7 Hz, 2H) (HAr, m, 3H), 9.50 (CHO, s, 1H), 11.1 (HOAr, s, 1H, D2 O exch.); m/z, M+ (%), 248.2 (3). Calculated for C16 H24 O2 , 248.4. 2.9.2. 2-Hydroxy-3-(1,1,3,3-tetramethylbutyl) benzaldehyde (17) 2-(1,1,3,3-Tetramethylbutyl)phenoxymagnesium bromide obtained from bromoethane (0.75 cm3 , 0.011 mol), magnesium turnings (0.38 g, 0.016 mol) and 2-(1,1,3,3-tetramethylbutyl)phenol (2.00 g, 0.011 mol) was formylated by the addition of paraformaldehyde (1.27 g, 0.027 mol) and HMPA (1.91 cm3 , 0.011 mol) to give after reaction the product as a yellow oil (1.27 g, 55.9%), which was puried as before; Rf 0.71 (solvent E); max (lm, cm1 ), 3400, 1250 (OH), 1710 (C=O), 1600 (C=C), 1390 (CO); H (CCl4 ), 0.67 (Me3 C, s, 9H), 1.37 (Me2 CAr, s, 6H), 1.90 (CH2 , s, 2H), 6.377.37 (HAr, m, 3H), 9.50 (CHO, s, 1H), 11.53 (OH, s, 1H, D2 O exch.); m/z, M+ (%) 234.2 (4.3). Calculated for C16 H24 O2 , 248.4, 2-hydroxy-3-(1,1,3,3tetramethylbutyl)phenol.
190
2.10. 2-Hydroxy-5-alkylbenzaldehtdes 2.10.1. 2-Hydroxy-5-t-butylbenzaldehyde (18, R = t-Bu) 4-t-Butylphenoxymagnesium bromide was prepared from bromoethane (4.9 cm3 , 0.066 mol), magnesium turnings (1.70 g, 0.071 mol) and 4-t-butylphenol (10.00 g, 0.066 mol). Formylation by reaction with paraformaldehyde (7.59 g, 0.165 mol) and HMPA (11.5 cm3 , 0.066 mol) afforded the product which was puried by dry-column ash chromatography, as before, to give a yellow oil (9.90 g, 83.5%), Rf 0.75 (solvent E); max (lm, cm1 ), 3200, 1180 (OH), 1680 (C=O), 1590 (C=C), 1380 (CO); H (CCl4 ), 1.23 (Me3 C, s, 9H), 6.507.30 (HAr, m, 3H), 9.47 (CHO, s, 1H), 10.37 (OH, s, D2 O exch.); m/z, M+ (%), 178.3 (22.8), M+ + 1 179.3 (3.0). Calculated for C11 H14 O2 , 178.2. 2.10.2. 2-Hydroxy-5-(1,1,3,3-tetramethylbutyl) benzaldehyde (18, R = t-C8 H17 ) 4-(1,1,3,3-Tetramethylbutyl)phenoxymagnesium bromide was obtained from bromoethane (8.9 cm3 , 0.12 mol), magnesium turnings (3.00 g, 0.125 mol) and 4-(1,1,3,3-tetramethylbuytl)phenol (25.00 g, 0.12 mol) and formylated by reaction with paraformaldehyde (13.8 g, 0.30 mol) and HMPA (20.9 cm3 , 0.12 mol) to afford the crude product which was puried on silica gel G by column chromatography, to give a yellow oil (21.15 g, 74.5%), Rf 0.71 (solvent E); max (lm, cm1 ), 3200, 1190 (OH), 1680 (C=O), 1590 (C=C), 1370 (CO); H (CCl4 ) (Me3 C, s, 9H), 1.23 (Me2 CAr, s, 6H), 1.57 (CH2 , s, 2H), 6.507.47 (HAr, m, 3H), 9.53 (CHO, s, 1H), 1.47 (HO, s, 1H, D2 O exch.); m/z, M+ (%), 234.5 (7.0), M+ + 1 235.5 (1.1). Calculated for C15 H22 O2 , 234.3. 2.10.3. 2-Hydroxy-5-n-nonylbenzaldehyde (18, R = n-C9 H19 ) 4-n-Nonylphenoxy magnesium bromide was prepared from bromoethane (0.67 cm3 , 0.009 mol), magnesium turnings (0.34 g, 0.014 pmol) and 4nonylphenol (2.00 g, 0.009 mol) and formylated by reaction with paraformaldehyde (1.04 g, 0.023 mol) and HMPA (1.6 cm3 , 0.009 mol). The crude product was puried by dry-column ash chromatography to give a yellow oil (1.86 g, 82.7%), Rf 0.73; max
(lm, cm1 ), 3300, 1210 (OH), 1680 (C=O), 1590 (C=C), 1380 (CO); H (CCl4 ), 0.791.68 [(CH2 )7 , Me, m, 17H], 2.502.68 (CH2 Ar, t, J 7 Hz, 2H), 6.737.43 (HAr, m, 3H), 9.75 (CHO, s, 1H), 10.95 (OH, s, 1H, D2 O exch.); m/z, M+ (%), 248.4 (3.2), M+ + 1, 249.4 (3.9). Calculated for C16 H24 O2 , 248.4. 2.10.4. 2-Hydroxy-5-(3,5,5-trimethylhexyl) benzaldehyde (18, R = t-C9 H19 ) (i) 4-(3,5,5-Trimethylhexyl)phenoxymagnesium bromide obtained from the reaction of bromoethane (3.4 cm3 , 0.045 mol), magnesium turnings (1.20 g, 0.05 mol) and 4-(3,5,5-trimethylhexyl)phenol (10.00 g, 0.045 mol) was formylated by reaction with paraformaldehyde (5.18 g, 0.09 mol) and HMPA (7.8 cm3 , 0.045 mol). The crude product was puried by column chromatography on silica gel G to give a pale yellow oil (8.26 g, 73.3%), Rf 0.69 (solvent E); max (lm, cm1 ), 3200, 1180 (OH), 1680 (C=O), 1590 (C=C), 1380 (CO); H (CCl4 ), 0.672.20 (C9 H19 , m, 19H), 6.507.30 (HAr, M, 3H), 9.47 (CHO, s, 1H), 10.40 (OH, s, 1H, D2 O exch.); m/z, M+ (%), 248.3 (5.4), M+ + 1, 249.1 (1.3). Required for C16 H24 O2 , 248.4. (ii) This compound was also obtained by the acid hydrolysis of the commercial reagent, Acorga (2hydroxy-5-(3,5,5-trimethylhexyl)benzaldoxime). A 50:50 mixture of the oxime and nonylphenol (30.0 g) and 20% aqueous sulphuric acid was stirred and warmed at 6065 C over 16 h, with monitoring by TLC (solvent F). Upon completion of reaction, the cooled mixture was extracted with diethyl ether (200 cm3 ). The ethereal extract was washed with saturated brine (4 100 cm3 ), dried (magnesium sulphate), concentrated and the residue puried dry-column ash chromatography (light petroleum/diethyl ether with gradient elution) to give 2-hydroxy-5-(3,5,5trimethylhexyl)benzaldehyde as a yellow oil (11.20 g, 79,2%) based on a 50% oxime/nonylphenol composition. The product was chromatographically and spectroscopically identical with the formylation product (18).
191
2.10.5. 2-Hydroxy-3-chloro-5-(1,1,3,3tetramethylbutyl)benzaldehyde (20, R = t-C8 H17 ) Firstly, Scheme 3 (b), 4-(1,1,3,3-tetramethylbutyl) phenol (15.01 g, 0.073 mol) in carbon tetrachloride (300 cm3 ) was chlorinated at ambient temperature over 4 h (TLC monitoring, solvent J, to avoid dichlorination). After completion of reaction, air was admitted to remove excess chlorine and the HCl formed. Concentration gave a yellow oil (16.80 g, 96.0%). 2-Chloro4-(1,1,3,3-tetramethylbutyl)phenoxymagnesium bromide was formed from the addition of ethyl magnesium bromide [prepared from bromoethane (8.72 cm3 , 0.08 mol), in diethyl ether (75 cm3 ) and magnesium turnings (2.88 g, 0.12 mol) in diethyl ether (50 cm3 )] to 2-chloro-4-(1,1,3,3-tetramethylbutyl)phenol (19.46 g, 0.08 mol) in diethyl ether (100 cm3 ) and the stirred reaction mixture was left at ambient temperature for 16 h, after which the ether was removed by distillation and replaced with benzene (100 cm3 ). Paraformaldehyde (9.20 g, 0.20 mol) and HMPA (13.9 cm3 , 0.08 mol) were added and the mixture was reuxed for 6 h with TLC monitoring (solvent E). The cooled mixture was acidied with dilute sulphuric acid, extracted with diethyl ether (200 cm3 ) and the ethereal extract was washed with saturated brine (5 150 cm3 ), dried with magnesium sulphate, ltered and concentrated in vacuo to give the crude product. This was puried by column chromatography on silica gel G (chloroform/6080 C, light petroleum with gradient elution). The product was obtained as a yellow oil (18.05 g, 83.1%); Rf 0.72 (solvent E); max (lm, cm1 ), 3420, 1180 (OH), 1670 (C=O), 1610 (C=C), 1370 (CO); H (CCl4 ), 0.77 (Me3 C, s, 9H), 1.35 (CH2 , s, 2H), 7.3,7.3 (HAr, 2s, 2H), 9.60 (ArCHO, s, 1H), 10.83 (HOAr, s, 1H, D2 O exch.); m/z, M+ (%), 268.2 (5.2), 270.2 (1.7). 2.11. Reduction of 2-hydroxy-3-, 4- and 5-alkylbenzaldehydes In a general method, a stirred solution of the aldehyde (0.005 mol) in methanol (30 cm3 ), cooled to below 0 C (icesalt bath), was slowly treated with sodium borohydride (0.01 mol) while the reaction temperature was kept below 0 C. The reaction mixture was allowed to warm to ambient over 16 h and completion of reduction monitored by TLC (solvent E). After the addition of diethyl ether (100 cm3 ), the
ethereal solution was washed with dilute sulphuric acid (4 100 cm3 ), dried (magnesium sulphate) ltered and concentrated in vacuo to afford the crude product which was puried either by column chromatography or recrystallisation. 2.11.1. 2-Hydroxymethyl-5-n-butylphenol (12, R1 = n-Bu) 2-Hydroxy-4-n-butyl benzaldehyde (1.81 g, 0.01 mol) and sodium borohydride (0.76 mol), by the general method, gave the crude product which was recrystallised (6080 C light petroleum) to afford white needles, mp 66.767.6 C (1.10 g, 60.1%); Rf 0.15 (solvent C). Found, C, 73.29; H, 9.27. Required for C11 H16 O, C, 73.30; H, 9.95%; max (KBr disc, cm1 ), 3440, 1000 (OH, pr. alc.), 3180, 1250 (OH, phenol), 1620 (C=C), 1410, 1280 (CO); H (CDCl3 ), 0.861.80 [(CH2 )2 , Me, m, 7H], 2.02.67 (CH2 Ar, HOCH2 , t on bs, 3H, D2 O exch.), 4.80 (HOCH2 Ar, s, 2H), 6.576.97 (HAr, m, 3H), 7.20 (HOAr, s, 1H, D2 O exch.); m/z, M+ (%), 180.4 (18.4), M+ + 1, 181.4 (2.1), M+ H2 O, 162.4 (7.8). 2.11.2. 2-Hydroxymethyl-5-t-butylphenol (12, R1 = t-Bu) By the general procedure, 2-hydroxy-4-t-butylbenzaldehyde (9.34 g, 0.05 mol) and sodium borohydride (3.97 g, 0.10 mol) afforded the crude product which was recrystallised (6080 C light petroleum/benzene) to give white uffy crystals, mp 95.996.3 C (6.51 g, 68.9%); Rf 0.17 (solvent C). Found, C, 73.27; H, 8.67. Required for C11 H16 O, C, 73.30; H, 8.95%; max (KBr disc, cm1 ), 3350, 1000 (OH, pr. alc.), 3250, 1210 (OH, phenol), 1590 (C=C), 1360, 1290 (CO); H (CDCl3 ) 1.27 (Me3 C, s, 9H), 2.0 (HOCH2 Ar, bs, 1OH, D2 O exch.), 4.80 (HOCH2 Ar, s, 2H), 6.837.06 (HAr, m, 3H), 7.17 (HOAr, s, 1H, D2 O exch.); m/z, M+ (%), 180.2 (15.0), M+ + 1, 181.2 (1.4%). 2.11.3. 2-Hydroxymethyl-5-n-octylphenol (12, R1 = n-C8 H17 ) 2-Hydroxy-4-n-benzaldehyde (0.93 g, 0.004 mol) and sodium borohydride (0.30 g, 0.008 mol) gave the crude product which was crystallised (4060 C light petroleum/diethyl ether) to give white needles, mp 85.886.6 C (0.50 g, 53.2%); Rf 0.22 (solvent C). Found, C, 76.38; H, 9.95. Required for C15 H24 O, C, 76.23; H, 10.24%; max (KBr disc, cm1 ), 3440, 1000
192
(OH, pr. alc.), 3240, 1210 (OH, phenol), 1600 (C=C), 1390, 1280; H (CDCl3 ), 0.861.53 [(CH2 )6 , Me, m, 15H], 2.13 (CH2 Ar, t, J 7 Hz, 2H), 2.50 (HOCH2 , bs, 1H, D2 O exch.), 4.70 (HOCH2 Ar, s, 2H), 6.637.17 (HAr, HO, m, 4H, 1H, D2 O exch.); m/z, M+ (%), 235.9 (8.2), M+ H2 O, 218.0 (5.2). 2.11.4. 2-Hydroxymethyl-5-n-nonylphenol (12, R1 = n-C9 H19 ) 2-Hydroxy-4-n-nonyl benzaldehyde (1.86 g, 0.007 mol) and sodium borohydride (0.57 g, 0.014 mol) afforded the crude product which was recrystallised as for the octyl compound to give white needles, mp 88.789.1 C (1.53 g, 81.8%); Rf 0.35 (solvent E). Found, C, 76.77; H, 10.38. Required for C14 H26 O, C, 76.77; H, 10.47%; max (KBr disc, cm1 ), 3440, 1000 (OH, pr. alc.), 3180, 1220 (OH, phenol), 1595 (C=C), 1410, 1280 (CO); H (CDCl3 ) 0.871.45 [(CH2 )7 , Me, m, 17H], 1.56 (HOCH2 Ar, bs, 1H), 2.442.62 (CH2 Ar, t, J 7 Hz, 2H), 4.77 (HOCH2 Ar, s, 2H), 6.597.21 (HAr, HOAr, m, 4H, 1H, D2 O exch.); m/z, M+ (%), 250.1 (16.4), M+ + 1, 251.1 (2.1), M+ H2 O, 232.0 (8.9). 2.11.5. 2-Hydroxymethyl-5-n-undecylphenol (12, R1 = n-C11 H23 ) 2-Hydroxy-4-n-undecylbenzaldehyde (2.05 g, 0.007 mol) and sodium borohydride (0.53 g, 0.014 mol) gave the crude product which was recrystallised to obtain white needles, mp 90.491.4 C (1.42 g, 68.9%); Rf 0.22 (solvent C). Found, C, 77.84; H, 10.86. Required for C18 H30 O, C, 77.66; H, 10.86%; max (KBr disc, cm1 ), 3450, 1000 (OH, pr. alc.), 3060, 1210 (OH, phenol), 1590 (C=C), 1410, 1260 (CO); H (CDCl3 ) 0.871.74 [(CH2 )9 , Me, m, 21H], 2.342.61 (CH2 Ar, HOCH2 , t on bs, 3H, 1H, D2 O exch.), 4.76 (HOCH2 Ar, s, 2H), 6.577.10 (HAr HOAr, m, 4H, 1H, D2 O exch.); m/z, M+ (%), 278.0 (36.6), M+ + 1, 279.1 (8.1). 2.11.6. 2-Hydroxymethyl-6-n-nonylphenol (15, R1 = n-C9 H19 ) 2-Hydroxy-3-n-nonylbenzaldehyde (1.17 g, 0.005 mol) and sodium borohydride (0.38 g, 0.01 mol) were reacted by the general method and the crude product puried by dry-column ash chromatography to give a pale yellow oil (0.91 g, 77.1%), Rf 0.50 (solvent E). Found, C, 76.87; H, 9.93. Required for C16 H26 O2 ,
C, 76.75; H, 10.47%; max (lm, cm1 ), 3350 (OH), 1220, 1020 (OH, phenol, pr. alc.), 1600 (C=C), 1380, 1260 (CO); H (CDCl3 ), 0.831.45 [(CH2 )7 , Me, m, 17H], 2.152.23 (CH2 Ar, t, J 7 Hz, 2H), 2.25 (HO, s, HOCH2 Ar, D2 O exch.), 4.77 (HOCH2 Ar, s, 2H), 6.077.33 (HAr, m, 3H), 7.52 (HOAr, s, 1H, D2 O exch.); m/z, M+ (%), 250.2 (20.3), M+ + 1, 251.2 (3.4), M+ H2 O, 232.2 (18.0). 2.11.7. 2-Hydroxymethyl-6-(1,1,3,3-tetramethylbutyl) phenol (15, R1 = t-C8 H17 ) 2-Hydroxy-3-(1,1,3,3-tetramethylbutyl)benzaldehyde (0.94 g, 0.004 mol), and sodium borohydride (0.30 g, 0.008 mol) gave the crude product which was puried by dry-column ash chromatography (light petroleum, diethyl ether with gradient elution) to give white needles, mp 74.175.1 C (0.65 g, 68.7%), Rf 0.64 (solvent E). Found, C, 76.22; H, 10.52. Required for C15 H24 O, C, 76.23; H, 10.24%; max (KBr disc, cm1 ), 3400, 1090 (OH, pr. alc), 3180, 1250 (OH, phenol), 1620 (C=C), 1410, 1280 (CO, phenol and pr. alc.); H (CCl4 ), 0.73 [ArCMe2 CH2 C(Me)3 , s, 9H], 1.40 (ArCMe2 , s, 6H), 1.87 (HOCH2 Ar, s, 1H, D2 O exch.), 1.93 (ArCMe2 CH2 , s, 2H), 4.67 (HOCH2 Ar, s, 2H), 6.477.07 (HAr, m, 3H), 7.40 (HOAr, s, 1H, D2 O exch.); m/z, M+ (%), 235.9 (6.7), M+ + 1, 236.9 (1.0). 2.11.8. 2-Hydroxymethyl-4-t-butylphenol (19, R = t-Bu) 2-Hydroxy-5-t-butylbenzaldehyde (9.90 g, 0.055 mol) and sodium borohydride (4.16 g, 0.10 mol) gave the crude product which was recrystallised to give white needles, mp 85.386.1 C (6.71 g, 67.6%); Rf 0.26 (solvent E). Found, C, 73.05; H, 8.70. Required for C11 H16 O, C, 73.30; H, 8.95%; max (KBr disc, cm1 ), 3350, 1000 (OH, pr. alc.), 3250, 1200 (OH, phenol), 1590 (C=C), 1380, 1290 (CO); H (CDCl3 ), 1.23 (Me3 C, s, 9H), 2.02.23 (HOCH2 Ar, bs, 1H, D2 O exch.), 4.63 (HOCH2 Ar, s, 2H), 6.477.03 (HAr and HOAr, m, 4H, 1H, D2 O exch.); m/z, M+ (%), 180.3 (19.6), M+ + 1, 181.3 (2.0), M+ H2 O, 162.3 (21.5). 2.11.9. 2-Hydroxymethyl-4-(1,1,3,3-tetramethylbutyl) phenol (19, R = t-C8 H17 ) 2-Hydroxy-5-(1,1,3,3-tetramethyl)benzaldehyde (15.46 g, 0.066 mol) with sodium borohydride (4.91 g,
193
0.13 mol) gave the crude product which was recrystallised (4060 C light petroleum/diethyl ether) to afford white crystals, mp 83.584.4 C (12.73, 81.6%); Rf 0.20 (solvent E); max (KBr disc, cm1 ), 3530, 1000 (OH, pr. alc.), 3260, 1180 (OH, phenol), 1610 (C=C), 1380, 1270 (CO); H (CCl4 ), 0.70 (Me3 C, s, 9H), 1.27 (Me2 CAr, s, 6H), 1.60 (CH2 Me2 CAr, s, 2H), 3.27 (HOCH2 Ar, bs, 1H, D2 O exch.), 4.57 (HOCH2 Ar, s, 2H), 6.437.0 (HAr, m, 3H), 7.33 (HOAr, bs, 1H, D2 O exch.). Found, M+ , 236.1777. Required for C15 H24 O, 236.1776; m/z, M+ (%), 236.8 (34.5), M+ + 1, 237.9 (4.1). 2.11.10. 2-Hydroxymethyl-4-n-nonylphenol (19, R = n-C9 H19 ) 2-Hydroxy-5-n-nonylbenzaldehyde (0.61 g, 0.002 mol) and sodium borohydride (0.18 g, 0.004 mol) afforded the crude product which was recrystallised (4060 C, light petroleum/diethyl ether) to give white platelets, mp 97.497.9 C (0.35 g, 57.4%); Rf 0.27 (solvent E). Found, C, 76.88; H, 10.68. Required for C16 H26 O, C, 76.75; H, 10.47%; max (KBr disc, cm1 ), 3440, 1130 (OH, pr. alc.), 3170, 1220 (OH, phenol), 1595 (C=C), 1390, 1280 (CO); H (CDCl3 ), 0.771.67 [(CH2 )7 , Me, m, 17H], 1.83 (HOCH2 Ar, s, 1H, D2 O exch.), 2.232.53 (CH2 Ar, t, J 7 Hz, 2H), 4.63 (HOCH2 Ar, s, 2H), 6.476.93 (HO and HOAr, 4H, 1H, D2 O exch.); m/z, M+ (%), 250.1 (30.8), M+ + 1, 251.1 (3.9), M+ H2 O, 232.1 (22.4). 2.11.11. 2-Hydroxymethyl-4-(3,5,5-trimethylhexyl) phenol (19: R = t-C9 H19 ) (i) From reduction: 2-Hydroxy-5-(3,5,5-trimethylhexyl)benzaldehyde (11.20 g, 0.045 mol) reacted with sodium borohydride (3.80 g, 0.90 mol) afforded the crude product which was puried by dry-column ash chromatography (light petroleum/diethyl ether with gradient elution) to give a pale yellow oil (8.13 g, 63.7%); Rf 0.32 (solvent E); max (lm, cm1 ), 3350 (OH), 1190 (OH, phenol), 1010 (OH, pr. alc.), 1260 (C=C), 1390, 1620 (CO); H (CDCl3 ), 0.431.83 (C9 H19 , m, 19H), 2.63 (HOCH2 Ar, bs, 1H, D2 O exch.), 4.77 (HOCH2 Ar, s, 2H), 6.607.23 (HAr and HOAr, m, 4H, 1H, D2 O exch.); m/z, M+ (%), 250.1 (9.5), M+ + 1, 251.1 (1.2). Found, M+ , 250.1934. Required for C16 H26 O, 250.1933.
(ii) From hydroxymethylation: To 4-(3,5,5-trimethylhexyl)phenol (11.44 g, 0.052 mol), stirred and heated to 60 C, 3 M sodium hydroxide (1 cm3 ) was added, to raise the pH to 1011, and then 37% aqueous formaldehyde (5.4 cm3 , 0.067 mol) The reaction mixture was stirred and heated for 24 h, cooled, extracted with diethyl ether (100 cm3 ) and the extract washed with dilute HCl (2 100 cm3 ), saturated brine (3 100 cm3 ), dried (magnesium sulphate), ltered and concentrated to give the crude product which was puried by dry-column ash chromatography (4060 C, light petroleum/diethyl ether with gradient elution) to afford a pale yellow oil (3.90 g, 30.0%) consisting of 2-hydroxymethyl-4-(3,5,5trimethylhexyl)phenol; Rf 0.29 (solvent C); max (lm, cm1 ), 3350 (OH), 1620 (C=C), 1390, 1260 (CO); H (CCl4 ), 0.371.57 (C9 H19 , m, 19H), 3.103.87 (HOCH2 Ar, bs, 1H, D2 O exch.), 4.50 (HOCH2 Ar, s, 2H), 6.336.93 (HAr and HOAr, m, 4H, 1H, D2 O exch.); m/z, M+ (%), 250.4 (19.8), M+ + 1, 251.4 (3.2). Calculated for C16 H26 O2 , 250.1933. Found, 250.1932. 2.11.12. 2-Hydroxymethyl-6-chloro-4-(1,1,3,3tetramethylbutyl)phenol (21, R = t-C8 H19 ) 2-Hydroxy-3-chloro-5-(1,1,3,3-tetramethylbutyl) benzaldehyde (9.42 g, 0.035 mol) and sodium borohydride (2.65 g, 0.07 mol), by the general method, afforded (TLC monitoring, solvent E) the crude product which was puried by dry-column ash chromatography to give a pale yellow oil (7.34 g, 77.3%); Rf 0.35 (solvent E); max (lm, cm1 ), 3340 (OH), 1610 (C=C), 1370, 1260 (CO), 1180, 1020 (OH, pr. alc.); H (CDCl3 ) 0.73 (Me3 C, s, 9H), 1.27 (Me2 C, s, 6H), 1.62 (CH2 CMe2 C, s, 2H), 3.53 (HOCH2 Ar, s, 1H, D2 O exch.), 4.60 (HOCH2 Ar, s, 2H), 6.887.05 (HAr and HOAr, 3s, 3H, 1H, D2 O exch.); m/z, M+ (%), 270.3 (13.0), 272.4 (4.2). Found, M+ , 270.1389. Calculated for C15 H23 O2 Cl, 270.1386. 2.12. Synthesis of 2-hydroxymethyl-3-n-alkylphenols from ethyl 2-methoxy-6-alkylbenzoates 2.12.1. Ethyl 2-methoxy-6-alkylbenzoates (22) To lithium diisopropylamide (LDA), prepared from diisopropylamine (0.14 mol) and n-butyllithium (0.12 mol) in dry THF (40 cm3 ), under nitrogen, ethyl
194
2-methoxy-6-methylbenzoate (0.1 mol) in dry THF (60 cm3 ) was added at 70 C. After reaction to complete formation of the anion (deep red coloration) during 30 min, HMPA (10% v/v of the total volume) and the bromoalkane (0.13 mol) in dry THF (20 cm3 ) were added at 70 C. The reaction mixture was left for 4 h and then allowed to warm to ambient temperature. To the now golden-brown solution, methylated spirit (60 cm3 ) was added and after stirring for 6 h, the mixture was acidied with excess 3 M sulphuric acid and extracted with diethyl ether (2 200 cm3 ) followed by ethyl acetate (2 200 cm3 ). The combined extracts were washed with saturated sodium hydrogen carbonate (2 200 cm3 ), then with saturated brine (4 200 cm3 ), dried (magnesium sulphate), ltered and the ltrate concentrated to afford the crude product which was puried by column chromatography. 2.12.2. Ethyl 2-hydroxy-6-n-alkylbenzoates (23) (ethyl 6-n-alkylsalicylates) The alkylmethoxy derivatives (0.01 mol) in dry dichloromethane (50 cm3 ) were demethylated at 78 C with boron tribromide (0.02 mol) in dichloromethane (20 cm3 ) and the mixture then allowed to warm to ambient temperature over 16 h. The excess reagent was hydrolysed with water (25 cm3 ) and the phenolic product extracted with diethyl ether (100 cm3 ). The ethereal extract was washed with saturated brine (3 100 cm3 ) until neutral, dried with magnesium sulphate, ltered and the solvent evaporated in vacuo. The crude product was puried by column chromatography. 2.12.3. 2-Hydroxymethyl-3-n-alkylphenols (24) Ethyl 2-hydroxy-6-methylbenzoate and ethyl 2methoxy-6-methylbenzoate were prepared as described (Hauser and Pogany, 1980). 2.12.4. Ethyl 2-hydroxy-6-n-butylbenzoate (23, R = n-Pr) Ethyl 2-methoxy-6-n-butylbenzoate (4.00 g, 0.02 mol) and 1-bromopropane (2.4 cm3 ) gave the crude product which was puried by dry-column ash chromatography to give a golden oil (3.24 g, 66.5%); Rf 0.33 (solvent F); max (lm, cm1 ), 1730 (C=O), 1600 (C=C), 1270, 1250 (CO); H (CCl4 ), 0.831.37 [(CH2 )2 , 2Me, m, 10H], 2.262.50 (CH2 Ar, t, J 7 Hz, 2H), 3.6 (OMe, s, 3H), 3.94.26 (OCH2 , q, J 7 Hz,
2H), 6.36.96 (HAr, m, 3H); m/z, M+ (%), 236.2 (38.9), M+ + 1, 237.2 (6.3). Required for C14 H20 O3 , 236.3. Demethylation afforded a crude product which was puried by dry-column ash chromatography to give a golden brown oil (1.49 g, 58.7%), ethyl 2-hydroxy-6n-butylbenzoate and a solid (white needles from 40 to 60 C, light petroleum), 2-hydroxy-6-n-butylbenzoic acid, mp 114.2115.0 C (0.51 g, 23.0%); for the ester, Rf 0.49 (solvent F); max (lm, cm1 ), 3400, 1220 (OH), 1650 (C=O), 1600 (C=C); H (CDCl3 ), 0.531.70 [(CH2 )2 , 2Me, 10H], 2.252.90 (CH2 Ar, t, J 7 Hz, 2H), 4.104.47 (OCH2 , q, J 7 Hz, 2H), 6.357.20 (HAr, m, 3H), 11.20 (HOAr, s, 1H, D2 O exch.); m/z, M+ (%), 222.2 (34.5), M+ + 1, 223.3 (6.4). Required for C13 H18 O3 , 222.3; for the acid, Rf 0.01 (solvent F); max (KBr disc, cm1 ), 3400, 1220 (OH), 2600, 1600 (OH, acid with internal H-bonding), 1650 (C=O), 1440, 1310 (CO); H (CCl4 ), 0.501.77 [(CH2 )2 , Me, m, 7H], 2.532.93(CH2 Ar, t, J 7 Hz, 2H), 6.237.10 (HAr, m, 3H), 10.87 (OH, HO2 C, s, 2H, D2 O exch.); m/z, M+ (%), 194.1 (33.7), M+ + 1, 195.1 (4.4). Required for C11 H14 O3 , 194.2. 2.12.5. Ethyl 2-hydroxy-6-n-octylbenzoate (23, R = n-C7 H15 ) By the general procedure, ethyl 2-methoxy-6-methylbenzoate (8.00 g, 0.041 mol) and 1-bromoheptane (8.2 cm3 , 0.052 mol) reacted to give the crude product which was puried by dry-column ash chromatography to give a golden oil (5.93 g, 49.25%); max (lm, cm1 ), 1730 (C=O), 1600 (C=C), 126-, 1250 (C=O, ether and ester); H (CDCl3 ), 0.791.67 [(CH2 )6 , 2Me, m, 18H], 2.272.76 (CH2 Ar, t, J 7 Hz, 2H), 3.76 (MeO, s, 3H), 4.224.49 (OCH2 , q, J 7 Hz, 2H), 6.647.30 (HAr, m, 3H); m/z, M+ (%), 292.1 (18.1), M+ + 1, 293.1 (2.7), M+ OEt, 247.0 (24.7). Required for C18 H28 O3 , 292.2. Demethylation gave a cream coloured solid which was puried by dry-column ash chromatography (6080 C, light petroleum/chloroform with gradient elution to afford a yellow oil (3.10 g, 54.9%) consisting of 2-hydroxy-6-n-octylbenzoate and 2hydroxy-6-n-octylbenzoic acid, mp 92.493.6 C (1.57 g, 30.9%); for the ester, Rf 0.44 (solvent F); max (lm, cm1 ), 3400, 1220 (OH), 1650 (C=O), 1600 (C=C), 1320, 1250 (CO); H (CDCl3 ), 0.801.63
195
[(CH2 )6 , 2Me, m, 18H], 2.532.97 (CH2 Ar, t, J 7 Hz, 2H), 4.274.54 (OCH2 , q, 2H), 6.507.33 (HAr, m, 3H), 11.13 (HOAr, s, 1H, D2 O exch.); m/z, M+ (%), 278.2 (17.9), M+ OEt, 232.2 (21.4). Required for C17 H26 O3 , 278.4; for the acid, Rf 0.04 (solvent F); max (KBr disc, cm1 ), 3400, 1220 (OH), 2600, 1610 (OH, acid H-bonding), 1650 (C=O), 1600 (C=C), 1440, 1310 (CO); H (CDCl3 ), 0.871.68 [(CH2 )6 , Me, m, 15H], 2.873.05 (CH2 Ar, t, J 7 Hz, 2H), 6.687.42 (HAr, m, 3H), 9.7512.75 (HOAr and HO2 C, 2H, D2 O exch.); m/z, M+ (%), 250.2 (33.1), M+ + 1, 251.1 (4.6). Required for C15 H22 O3 , 250.3. 2.13. Reduction of ethyl 6-n-alkylsalicylates to 2-hydroxymethyl-3-n-alkylphenols (24) General method: The ethyl 2-hydroxy-6-nalkylbenzoate (0.01 mol) in dry THF (30 cm3 ) was treated with an ice-cold suspension of lithium aluminium hydride (0.03 mol) in dry THF (20 cm3 ) under nitrogen. After completion of reaction (TLC monitoring) the excess reagent was destroyed with ethyl acetate (ca. 1 cm3 ), the mixture was then acidied with 3 M HCl and extracted with diethyl ether (100 cm3 ). The extract was washed with saturated brine until neutral, dried (anhydrous sodium sulphate), ltered and concentrated to give a crude product which was puried by dry-column ash chromatography. The method was also used for the corresponding acid. 2.13.1. 2-Hydroxymethyl-3-methylphenol (24, R = H) By the general method ethyl 2-hydroxy-6methylbenzoate (1.70 g, 0.009 mol) and lithium aluminium hydride (1.02 g, 0.027 mol) gave a crude product which was recrystallised (light petroleum) to yield white crystals, mp 105.6106.6 C (0.73 g, 56.1%); Rf 0.23 (solvent C). Found, C, 69.25; H, 7.22. Calculated for C8 H10 O3 , C, 69.55; H, 7.10%; max (KBr disc, cm1 ), 3300 (OH), 1210, 1040 (OH, phenol and pr. alc.), 1600 (C=C), 1330, 1290 (CO); H (CDCl3 ), 2.20 (MeAr, s, 3H), 2.45 (HOCH2 Ar, bs, 1H, D2 O exch.), 4.75 (HOCH2 Ar, s, 2H), 6.337.03 (HAr, m, 3H), 7.45 (HOAr, bs, 1H, D2 O exch.); m/z, M+ (%), 138.1 (46.2), M+ +1, 139.1 (4.3), M+ H2 O, 120.0 (63.4).
2.13.2. 2-Hydroxymethyl-3-n-butylphenol (24, R = n-Pr) By the general method, ethyl 2-hydroxy-6-nbutylbenzoate (1.91 g, 0.009 mol) and LAH (0.29 g, 0.03 mol) afforded the crude product. Similarly, 2hydroxy-6-n-butylbenzoic acid (0.51 g, 0.003 mol) and LAH (0.98 g, 0.009 mol) gave the same product which was puried by dry-column ash chromatography (chloroform/ethyl acetate, with gradient elution) to give white crystals (from 40 to 60 C, light petroleum), mp 54.955.7 C (1.59 g, 96.5%); Rf 0.29 (solvent C). Found, C, 73.05; H, 8.70. Required for C11 H16 O2 , C, 73.30; H, 8.95%; max (KBr disc, cm1 ), 3300 (OH), 1210, 1030 (OH, phenol and pr. alc.), 1600 (C=C), 1345, 1290 (CO); H (CDCl3 ), [(CH2 )2 , Me, m, 7H], 2.092.73 (CH2 Ar, t, J 7 Hz, 2H), 2.634.0 (HOCH2 Ar, s, 1H, D2 O exch.), 4.534.77 (HOCH2 Ar, s, 2H), 6.277.03 (HAr and HOAr, m, 4H, 1H, D2 O exch.); m/z, M+ (%), 180.1 (82.9), M+ + 1, 181.0 (9.4), M+ H2 O, 162.0 (49.3). 2.13.3. 2-Hydroxymethyl-3-n-octylphenol (24, R = n-C7 H15 ) By the general procedure, ethyl 2-hydroxy-6-noctylbenzoate (3.10 g, 0.011 mol) and LAH (1.25 g, 0.033 mol), and similarly 2-hydroxy-6-n-octylbenzoic acid (1.57 g, 0.006 mol) and LAH 0.68 g, 0.018 mol) together gave the crude product. Purication by drycolumn ash chromatography gave a clear viscous oil (combined batches, 2.79 g, 67.9%); Rf 0.31 (solvent C). Found, C, 76.08; H, 10.54. Required for C15 H24 O2 , C, 76.23; H, 10.24%; max (KBr disc, cm1 ), 3300 (D2 O); m/z, M+ (%), 236.1 (26.1), M+ + 1, 237.1 (3.7), M+ H2 O, 218.2 (9.2) (OH), 1190, 1040 (OH, phenol and pr. alc.), 1590 (C=C), 1350, 1250 (CO); H (CDCl3 ), [(CH2 )6 , Me, m, 15H], 2.442.62 (CH2 Ar and HOCH2 Ar, t, J 7 Hz, 2H and 1H, D2 O exch.), 4.85 (HOCH2 Ar, s, 2H), 6.607.20 (HAr and HOAr, m, 4H, 1H exch.). 3. Results and discussion 3.1. Sources of phenolic lipids The phenolic lipids (Fig. 1), from Anacardiaceae sources all require purication before semi-synthetic usage (Tyman, 1995). Of the variety of methods available, the process of phase separation (Tyman et al.,
196
1992) is applicable to both the isolation of anacardic acid and of cardanol, respectively, from natural and technical CNSL since it is essentially a mild ambient temperature method in which the highly unsaturated constituents are preserved intact. Additionally, the remaining component, namely cardol, is also simultaneously recoverable whereas in chemical or purely thermal methods it is lost. Technical CNSL is available commercially but with natural CNSL, although the technology exists to cut shells, while leaving the edible nut uncontaminated, the subsequent solvent extraction stage, or high pressure extrusion, has not yet been achieved on a commercial scale (M. Grimminger, Buhler-Miag Co., private communication). In a similar way, urushiol is processed in Japan and China but not generally available elsewhere. Thitsiol, the 4-alkenyl analogue (Tyman, 1973, 1979) of the 3-alkenyl-1,2diol, urushiol, was unfortunately not available for study as a borate complexant in the present work. However, although synthesis of all the constituents of these phenolic lipids has been achieved (Kozubek and Tyman, 1999; Tyman, 2001; Niimura et al., 1998), natural sources remain the source of supply. As well as the natural aromatic diols and semisynthetic o-hydroxymethylols described in the present study, the unsaturated side chains of methylated phenolic lipids have been polyhydroxylated (Durrani et al., 1982) to afford potential borate complexants. 3.2. Synthesis of 1,3-diols (2-hydroxymethylols) The Schemes 16 depict the essence of the present work namely to semi-synthesise and synthesise homologous members of the four structural isomers, namely 2-hydroxymethyl derivatives of 3-alk(en)yl-, 4-alkyl-, 5-alk(en)yl- and 6-alkylphenols in order to compare their relative borate complexation. 3.3. Anacardic alcohols, 2-hydroxymethyl-3-alk (en)ylphenols Lithium aluminium hydride reduction of C11 , anagigantic and C15 , anacardic acids (2) and (1), afforded the corresponding anacardic alcohols (6) and (5, n = 0, 2, 4, 6), respectively, as shown in Scheme 1. Generally, the use of methyl esters afforded slightly better yields than reduction of the corresponding acids. Thus, the methyl ester of (1) and the acid (1) gave
yields of 88.6 and 79.1%, respectively. Nevertheless, the additional step of esterication, either by the less attractive use of diazomethane, or more conveniently by esterication, offset this slight gain. 3.4. Homologous 2-hydroxymethyl-3-alkylphenols Homologous 2- hydroxymethyl- 3- alkylphenols were synthesised as shown in Scheme 2. Alkylation (Tyman and Visani, 1997; Carpenter et al., 1984) of ethyl 2-methoxy-6-methylbenzoate (Hauser and Pogany, 1980) afforded the required 6-alkyl derivative which was demethylated with boron tribromide (Durrani and Tyman, 1980) to give the corresponding salicylate. Reduction with lithium aluminium hydride furnished the methylol. Certain of the homologous 2-hydroxymethyl-3alkylphenols (24, R = H, n-C3 H7 and n-C7 H15 ) were synthesised by the alkylation of ethyl 2-methoxy-6methylbenzoate as depicted in Scheme 2 since the lower anacardic acids are not available from natural sources. The alkylation stage to give (22) was followed by demethylation with boron tribromide producing (23) and reduction of the ester with lithium aluminium hydride, as in Scheme 1, to afford the three compounds represented by 24. 3.5. Synthesis of 2-hydroxymethyl-4-alkylphenols Homologous 2 - hydroxymethyl- 4- alkylphenols were synthesised as shown in Scheme 3 from the appropriate 4-alkylphenol in the form of the phenoxymagnesiobromide by reaction with paraformaldehyde (Casiraghi et al., 1978) and reduction of the aldehyde product with sodium borohydride.(b) (iii), (iv) as in (a), respectively. The synthesis of certain homologous members of this group is shown in Scheme 3 (a) consisting of (19, R = t-Bu, t-C8 H17 , n-C9 H19 , t-C9 H19 ). Apart from the n-nonyl member the 4-alkyl-substituted phenols were all from petrochemical sources. Although as with the anacardic acids in Scheme 1, the methylols could be formed by hydride reduction of a carboxylic or carbethoxy substituent, we had found that either formylation (Casiraghi et al., 1978; Tyman, 1981) (J.H.P. Tyman and S.J.A. Iddenten, unpublished work) and reduction with sodium borohydride or, direct methylolation, were two alternative
197
procedures. In the case of the parent phenol (R = tnonyl) monoformylation proceeded regiospecically and borohydride reduction gave an overall 46.7% yield whereas hydroxymethylolation, which resulted in some disubstitution (2,6-dihydroxymethyl-4-3,5,5trimethylhexylphenol, 42.4%), gave 30.0% of the monohydroxymethyl compound, although the directness of the latter method is an advantage (this work with A. Ninagawa, will be reported elsewhere). In (b) Scheme 3, the synthesis of the chloro-derivative (21), OCS, namely, 2-hydroxymethyl-6-chloro-4-(1,1,3,4tetramethylutyl)phenol is shown. Monochlorination of t-octylphenol in carbon tetrachloride at ambient temperature gave a 96% yield of 2-chloro-4-t-octylphenol which was formylated to give 2-hydroxy-3-chloro-5(1,1,3,3-tetramethylbutyl)benzaldehyde (20) in 83.1% yield, sodium borohydride reduction of which gave 21 in 77.3% yield, in pure form. It appears that previous preparations of this extractant (Brown and Sanderson, 1978b), were impure and were employed contained both the starting material 4-t-octylphenol and its 2-methylol. 3.6. 2-hydroxymethyl-5-alk(en)ylphenols The parent C15 2-hydroxymethyl-5-alk(en)ylphenol, isoanacardic alcohol (9) was synthesised as depicted in Scheme 4, either, by the Kolbe carboxylation of cardanol to give isoanacardic acid (Durrani et al., 1980) (7) followed by lithium hydride reduction or, from isoanacardic aldehyde (8), available from the reaction of cardanoxymagnesium bromide with paraformaldehyde in the presence of HMPT, followed by reduction of (8) with sodium borohydride, or by hydroxymethylation in aqueous alkaline solution with formaldehyde. Hydroxymethylation of cardanol with formaldehyde in aqueous alkaline solution afforded isoanacardic alcohol (9) (37.3%), recovered cardanol (42.4%), together with small proportions of the 4-isomer (3.5%), the 2,4-disubstituted compound (7.1%) and less than 10% of more complex material. Based on the cardanol reacted, the conversion to the monomethylol was 71.2%. 3.7. Synthesis of homologous 2-hydroxymethyl-5-nalkylphenols In Scheme 5, the synthesis of certain homologous 2-hydroxymethyl-5-alkylphenols (12, R1 = n-Bu, t-
Bu., n-C8 H17 , n-C9 H19 and n-C11 H23 is shown. Wittig reaction (Maercker, 1965) of 3-hydroxybenzaldehyde with the required alkyltriphenylphosphonium bromide followed by catalytic hydrogenation of the respective alkene formed, gave the 3-alkylphenol (10). Formylation in the usual way of the phenoxymagnesium bromide and reaction with paraformaldehyde afforded the respective aldehyde (11) and thence by sodium borohydride reduction, the required product. Alternative procedures (Caplin and Tyman, 1982; Tyman et al., 2002) to 3-alkylphenols by reaction of 3-hydroxybenzaldehyde with 1-bromoalkanes in THF containing lithium, followed by catalytic hydrogenolysis, also afford excellent yields. 3.8. Synthesis of 2-hydroxymethyl-6-alkylphenols The synthesis of two homologous 2-hydroxymethyl6-alkylphenols is depicted in Scheme 6 (a and b). 2-n-Nonylphenol (13), obtained by a Wittig reaction with salicylaldehyde followed by catalytic hydrogenation, was formylated as the phenoxymagnesium bromide by reaction with paraformaldehyde to afford the aldehyde (14) which was reduced by sodium borohydride to give 2-hydroxymethyl-6-n-nonylphenol (15, R1 = n-C9 H19 ). The t-octyl analogue (15, R1 = tC8 H17 ) was synthesised by t-octylation of phenol to give 16, followed by formylation and reduction of the aldehyde product (17) with sodium borohydride. Alternative methods for formation of methylols by catalytic hydrogenation with copper chromite (Adkins, 1954), rhenium catalysts (Broadbent and Bartley, 1963) and by electrolytic reduction Ri and Covitz, 1974) are available, but were not examined in this present exploratory work. 3.9. Solvent extraction properties of 1,2- and 1,3-diols The complexation and solvent extraction of borate leading to the recovery of boric acid by compounds described in this account will be described in detail elsewhere. Unsaturated anacardic alcohol (5) appears to be a superior extractant to its iso-analogue (9) over a wide pH range. By contrast, OCS (21) and its dechloro analogue (19, R = C8 H17 ) and the 4-t-nonylphenol analogue (19, R = C9 H19 ) are only more effective at a higher pH but rapidly decline and are inferior
198
J.H.P. Tyman, S.K. Mehet / Chemistry and Physics of Lipids 126 (2003) 177199 Durrani, A.A., Goh, C.S., Tyman, J.H.P., 1982. Synthesis of oxidative degradation products from methylated component phenols of Anacardium occidentale. Lipids 17, 561 569. Folkestad, F.E., Loeiten, K.O., Mejdell, G.T., Gloer, T., Torvund, A., 1972. Removing boric acid and its salts from magnesium chloride solutions. Norway Patent 124026 (21 February). Gulati, A.S., Subba Rao, B.C., 1964. Drug analogues from the phenolic constituents of cashew nut-shell liquid. Indian J. Chem. 2, 337338. Hauser, F.M., Pogany, S.F., 1980. 2-Hydroxy-6-methylbenzoic acid derivatives. Synthesis 814815. Havighorst, C.R., 1963. New process separates borates from ore by extraction. Chem. Eng. 70, 228232. Klopfenstein, R.R., Arnold, D.S., 1966. Recent developments in solvent extraction technology. J. Met. 18, 11951197. Kozubek, A., Tyman, J.H.P., 1999. Resorcinolic lipids, the natural non-isoprenoid phenolic amphiphiles: their biological activity. Chem. Rev. 99, 126. Laan, I.A.M., Ward, J.P., 1987. Selective monoortho-alkylation of phenol with an aluminium catalyst. Chem. Ind. 3435. Lam, S.K., Tyman, J.H.P., 1982. The conversion of anacardic acid into urushiol, J. Chem. Soc., Perkin Trans. 1942 1952. Maercker, A., 1965. The Wittig reaction. Org. React. 14, 270 490. Matthews, A.J., Tyman, J.H.P., 1982. Compositional studies on Japanese lac (Rhus vernicifera) by chromatography and mass spectrometry. J. Chromatogr. 235, 149164. Mehet, S.K., 1988. The synthesis of phenolic lipids and their derivatives for use in the solvent extraction of boron. Ph.D. thesis, Brunel University. Niimura, N., Kamiya, Y., Sato, T., Katano, I., Miyakoshi, T., 1998. Synthesis of 3-[(8Z,11E,13Z)-8,11,13-pentadecatrienyl] catechol. Nihon Yukagakkaishi 47, 171178. Patel, M., Tyman, J.H.P., Manzara, A., 1981.Treatment of cashew nut-shell liquid. UK Patent Application 8100208 (6 January). Ri, M.R., Covitz, F.M., 1974. Introduction to organic electrochemistry. Dekker, New York, p. 168. Svares, E., Putnina, A., Kalve, I., Sennikova, L.M., Kirchanov, A., 1983. Extraction of boric acid by normal 1,3-diols. Zh. Neorg. Khim. 28, 23332337. Shvarts, E.M., Kalve, I., Telzhenskaya, P.N., 1995. Extraction of boric acid in the boric acid, sulphuric acid, water system. Latv. Kim. Z. 3/4, 8893. Tyman, J.H.P., 1973. Identication of the components of a novel fraction in Anacardium occidentale. J. Chem. Soc., Perkin Trans. 16391647. Tyman, J.H.P., 1979. Non-isoprenoid long chain phenols. Chem. Soc. Rev. 8, 499538. Tyman, J.H.P., 1981. Metal extraction and chemical purication. US Patent Application 587068. Tyman, J.H.P., 1983. Chemical purication method. UK Patent Application GB21529325A (24 October). Tyman, J.H.P., 1992. Separating cardanol and other naturallyoccurring phenols from technical cashew nut-shell liquid. UK Patent Application GB 2254323A (15 March).
at normal (neutral) pH values. Urushiol (4) is less effective over the whole pH range. However, in the presence of Aliquat 336 (tri-t-octylamine), the performance of unsaturated anacardic alcohol, isoanacardic alcohol, the 4-t-nonylphenol analogue and urushiol is enhanced, but again unsaturated anacardic alcohol and its iso analogue are the most effective of the semi-synthetic series of lipidic diols. The usage of diols from natural replenishable sources would enable fossil fuels to be employed preferentially for energy rather than for chemical uses. It is also relevant that certain phenolic lipid products from natural sources have been found to be more biodegradable than their petrochemical analogues (Tyman and Bruce, 1992; Tyman and Bruce, 2003).
Acknowledgements Borax Research are thanked for partial nancial support and for laboratory facilities.
References
Adkins, H., 1954. Catalytic hydrogenation of esters to alcohols. Org. React. 8, 127. Boesekin, J., 1913. Positions in space of the hydroxyl groups of polyhydroxy compounds. Conguration of the saturated glycols and of the - and -glucoses. Ber. 46, 26122628. Broadbent, H.S., Bartley, W.J., 1963. Rhenium catalysts VII rhenium(VI) oxide. J. Org. Chem. 28, 23452350. Brown, C.G., Sanderson, B.R, 1978a. BP 1514927 (21 June). Brown, C.G., Sanderson, B.R, 1978b. Solvent extraction of boron. Chem. Ind. 6873. Caplin, J., Tyman, J.H.P., 1982. The synthesis of 3-[(Z)-pentadec8-enyl]phenol and 3-[(Z,Z)-pentadec-8,11-dienyl]phenol. J. Chem. Res. (S), 3435. Carpenter, T.A., Evans, G.E., Leeper, F.J., Staunton, J., Wilkinson, M.R., 1984. Reactions of the carbanion from an orsellinate derivative with electrophiles. J. Chem. Soc., Perkin Trans. 10431049. Casiraghi, G., Casnati, G., Cornia, M., Pochini, A., Puglia, G., Sartoria, G., Ungaro, R., 1978. Selective reactions using metal phenoxides. J. Chem. Soc., Perkin Trans. 318 323. Durrani, A.A., Hawkes, A.J., Tyman, J.H.P., 1980. Polymer, reparation, and formulation for bonded particulate and brous materials. PCT Eur. Spec. 0015761 (7 March). Durrani, A.A., Tyman, J.H.P., 1980. A novel synthesis of homologous orsellinic acids. J. Chem. Soc., Perkin Trans. 1658 1666.
J.H.P. Tyman, S.K. Mehet / Chemistry and Physics of Lipids 126 (2003) 177199 Tyman, J.H.P., 1995. In: Atta-ur-Rahman (Ed.), The Role of Biological Materials in Synthesis, Studies in Natural Products Chemistry, vol. 17. Elsevier, Amsterdam, pp. 601654. Tyman, J.H.P., 1996. Studies in Organic Chemistry 52, Synthetic and Natural Phenols. Elsevier, pp. 465546 (Chapter 13). Tyman, J.H.P., 2001. The chemistry and biochemistry of anacardic acids. Recent research in lipids. Transworld Res. Network 5, 125145. Tyman, J.H.P., Bruce, I.E., 1992. Biodegradable surfactants derived from phenolic lipids. In: Tyman, J.H.P. (Ed.). Surfactants in Lipid Chemistry. Royal Society of Chemistry, Cambridge, pp. 159177. Tyman, J.H.P., Bruce, I.E. J. Surfactants Detergents, in press. Tyman, J.H.P., Visani, N., 1997. Synthesis of saturated anacardic acids and alkenyl and alkynyl analogues. J. Chem Res. (S), 1415.
199
Tyman, J.H.P., Muir, M., Johnson, R.A., Rokhgar, R., 1989. The extraction of natural cashew nut-shell liquid. J. Am. Oil Chemists Soc. 66, 553557. Tyman, J.H.P., Bruce, I.E., Payne, P., 1992. The phase separation of phenolic lipids from Anacardium occidentale. Nat. Prod. Lett. 1, 117120. Tyman, J.H.P., Schoeld, B.G., Khor, C.H., 2002. A synthesis of the phenolic lipid, 3-[(Z)-pentadec-8-enyl]catechol. Chem. Phys. Lipids 120, 101108. Vinogradov, E.E., 1962. Extraction of boric acid with isoamyl alcohol from hydrochloric acid solutions. Zh. Strukt. Khim. 7, 28132816. Vinogradov, E.E., Shamiryan, P.S., Tarasova, G.N., Ivanov, A.A., Panasyuk, G.P., 2001. The system, boric acid, lithium chloride, 2-ethylhexanol. Zh. Neorg. Khim. 46, 860 865.

The Separation and Synthesis of Lipidic 1,2-And 1,3-Diols From Natural Phenolic Lipids For The Complexation and Recovery of Boron

Încărcat de

Informații document

Descriere originală:

Titlu original

Drepturi de autor

Formate disponibile

Partajați acest document

Partajați sau inserați document

Opțiuni de partajare

Vi se pare util acest document?

Este necorespunzător acest conținut?

Drepturi de autor:

Formate disponibile

The Separation and Synthesis of Lipidic 1,2-And 1,3-Diols From Natural Phenolic Lipids For The Complexation and Recovery of Boron

Încărcat de

Drepturi de autor:

Formate disponibile

Chemistry and Physics of Lipids 126 (2003) 177199

S-ar putea să vă placă și