1-s2.0-S0009308403001154-main

Chemistry and Physics of Lipids 126 (2003) 177–199

The separation and synthesis of lipidic 1,2- and1,3-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 fromAnacardium occidentale andAnacardium 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-diolshave been synthesised from a range of synthetic 2-alkyl-, 3-alkyl- and 4-alkylphenols and from 6-alkylsalicylic acids. The natural1,2-diol, urushiol, fromRhus vernicifera has been purified. All these lipidic compounds have been studied for their complexationand 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 ofboron compounds

1. Introduction

The interaction between polyhydroxy compoundsand boric acid has been of interest since the clas-sical conductometric work on the absolute config-uration of glycols and of the�- and �-glucoses(Boesekin, 1913). More recent experimental workhas concentrated on the complexation and extrac-tion of boric acid by monohydric alcohols, such asisoamyl 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: [email protected] (J.H.P. Tyman).

2001), and notably by lipidic diols, 2-ethylhexane-1,3-diol (Brown and Sanderson, 1978b), nonane-1,3-diol, decane- and dodecane-1,3-diols (Shvartset al., 1995; Svares et al., 1983), and in thearomatic o-hydroxymethylphenolic (alkylsalicyl al-cohol) series, with 2-chloro-6-hydroxymethyl-4-isooctylphenol (Brown and Sanderson, 1978b). Someof these studies have led to commercial interest inthe prospect of recovery through solvent extractionas, for example, by the American Potash and Chem-ical Corporation (Havighorst, 1963; Klopfenstein andArnold, 1966), with ‘octylchlorosaligenin’, 2-chloro-6-hydroxymethyl-4-t-octylphenol (OCS) for the re-covery of boric acid from Californian salt lake brineshaving borate concentrations below those applicableto 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) 177–199

Fig. 1. Formulae of phenolic lipids and structures of unsaturated side chains b, c, d of1, 3 and b, c, d, e of4.

cases, where boron contamination is undesirable, forexample, in agricultural citrus crop cultivation, orin magnesium production (Folkestad et al., 1972),solvent extraction involving 2-ethylhexanol andiso-octanol in petroleum ether has found a role in the se-lective recovery/removal of boric acid. In the presentpreparative work, amongst the replenishable raw ma-terials used for the semi-synthesis of lipidic 1,3-diols,anacardic acid (1) (n = 0, 2, 4, 6) is the chief C15component of natural cashew nut-shell liquid (Tyman,1979, 1996), in Anacardium occidentale indigenousto India and Brazil and (2) the C11 analogue inAnac-ardium giganteum. In the industrial heat-processing ofcashew, the technical cashew nut-shell liquid formedby decarboxylation contains mainly the by-product,cardanol (3) (n = 0, 2, 4, 6). Urushiol (4) (n = 0, 2,

Scheme 1. Synthesis of anacardic alcohols (2-hydroxymethyl-3-alkylphenols). Reagents: (i) LiAlH4, THF; HCl.

4, 6) is the major aromatic C15 3-alkenyl-1,2-diol inRhus vernicifera (from Japan and China) and inRhustoxicodendron (Tyman, 1979, 1996).

The natural isomeric 4-alkenyl analogue, thitsiol,occurs in the Burmese lac tree,Melanorrhea usitata.Fig. 1depicts the structures of the first four materials.Anacardic acid (1) and cardanol (3) have unsaturatedside chains (b, c and d) while urushiol (4) has unsat-urated structures (b, c, d and e) (Fig. 1).

Fossil fuel-derived 4-t-butyl, 4-t-nonyl, and 4-t-octylphenol have served as starting materialsfor the synthesis of analogous saligenins, with 2-hydroxymethylphenolic structures.

The compounds synthesised, namely 2-hydroxy-methyl-3-alkyl-, 4-alkyl-, 5-alkyl- and 6-alkylphenols(isomeric saligenins) are depicted inScheme 1(5 and

J.H.P. Tyman, S.K. Mehet / Chemistry and Physics of Lipids 126 (2003) 177–199 179

Scheme 2. Synthesis of 2-hydroxymethyl-3-alkylphenols. Reagents: (i) LDA, THF, HMPA, RBr; H3O+, (ii) BBr3, CH2Cl2, −78◦C, H2O,(iii) LiAlH 4, THF; HCl.

Scheme 3. Synthesis of 2-hydroxymethyl-4-alkylphenols. Reagents: (a) (i) EtMgBr, Et2O, HMPA, (CH2O)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), LiAlH 4, THF; HCl, (iii) EtMgBr, Et2O, HMPA, (CH2O)n; HCl, (iv) NaBH4, MeOH, 0◦C; HCl, (v) NaOH, MeOH, HCHO.


Scheme 5. Synthesis of 3-n-alkylphenols, 2-hydroxy-4-n-alkyl-benzaldehydes and 2-hydroxymethyl-5-n-alkylphenols. Reagents: (i)RCH2P+(Ph)3Br−, BuLi, THF, (ii) Pd–C, H2, EtOH, (iii) EtMgBr, Et2O, HMPA, (CH2O)n; HCl, (iv) NaBH4, MeOH; HCl.

Scheme 6. Synthesis of 2-hydroxy-3-alkylbenzaldehydes and 2-hydroxymethyl-6-alkylphenols. Reagents: (a) (i) C8H17P+(Ph)3Br−, BuLi,THF, (ii) Pd–C, H2, EtOH, (iii) EtMgBr, Et2O, HMPA, (CH2O)n,; HCl, (iv) NaBH4, MeOH; HCl, (v) Al, �, C8H16; aqueous H2SO4,(vi) EtMgBr, Et2O, HMPA, (CH2O)n; HCl, (vii) NaBH4, MeOH; HCl.

6), Scheme 2(24), Scheme 3(19 and21), Scheme 4(9, R1 = H), Scheme 5(12) and Scheme 6(15)(Section 3). To aid structure/property correlation,homologous members of the structurally isomericsaligenins, not available from natural sources, weresynthesised to determine the role of chain length andthe position of the alkyl chain substituent in the arylring on the efficiency of the resultant boric acid ex-tractant. The effect of branching in the side chain wasstudied by a comparison of fossil fuel-derived syn-thetic compounds havingt-butyl, t-octyl and t-nonylside chains with those in the isomericn-alkyl series.

2. Experimental procedures

2.1. Materials

Cashew nuts, of Indian and Mozambique origin,were obtained from Gill, Duffas and Landauer, Lon-don, SE1 and half shells from Mr. M. Grimminger,Buhler Miag, Barnet, London. Technical cashew nut-shell liquid was obtained from 3M Research Ltd.,St Paul, MN, USA. Japanese lac was obtained withthe help of the Japanese Trade Centre, London, fromDr. M. Sato, Industrial Research Laboratory, Sendai,


Japan.A. giganteum was made available with thehelp of Prof. Tereza Pastore, University of Brasilia,Brazil.

Chemicals were obtained from Aldrich ChemicalCo. other thant-nonylphenol (3,5,5-trimethylhexyl-phenol) andt-octylphenol, which were both from ICI.

2.2. Chromatography

Analytical thin layer chromatography (TLC) waseffected with Whatman silica gel 60AMK6F plates(1 in. × 3 in.) having a 250�m layer and preparativeTLC with Merck silica gel 60GF (20 cm×20 cm) witha 1 mm layer. Solvents A to N had the following com-positions: A, chloroform:ethyl acetate (95:5); B, chlo-roform:ethyl acetate:formic acid (95:5:2); C, chloro-form:ethyl acetate (90:10); D, dichloromethane:lightpetroleum (40–60◦C) (50:50); E, diethyl ether:lightpetroleum (40–60◦C) (50:50); F, chloroform:lightpetroleum (60–80◦C) (50:50); G, acetone; H, chlo-roform:ethyl acetate (98:2); I, diethyl ether:lightpetroleum (40–60◦C) (40:60); J, chloroform:lightpetroleum (60–80◦C) (70:30); K, diethyl ether:lightpetroleum (40–60◦C):0.880 ammonia (70:30:4); L,diethyl ether:light petroleum (40–60◦C):formic acid(70:30:2); M, light petroleum (60–80◦C):chloroform(70:30); N, light petroleum (60–80◦C):chloroform(80:20).

For synthetic work, diethyl ether and benzenewere dried over anhydrous calcium chloride and thenovernight over sodium wire. Dry dichloromethane wasobtained by refluxing over calcium hydride prior todistillation. THF was dried by refluxing over sodiumwith benzophenone ketyl radical as indicator.

Column chromatography was carried out with BDHsilica gel, particle size 0.13–0.25 mm.

For flash chromatography, Merck kieselgel 60(230–400 mesh) was used, and for dry flash chro-matography, Merck kieselgel 60H and 60GF.

2.3. Spectroscopy

Infrared spectra were recorded on a Perkin Elmer1420 spectrophotometer.1H NMR spectra were de-termined with Varian T60 (60 mHz) and CFT20instruments with tetramethylsilane as internal stan-dard. Mass spectra were obtained on a modified AEIMS902 instrument and accurate mass determinations

were made by the SERC Mass Spectrometry Centreat the University College of Wales, Swansea.

2.4. Separations of phenolic lipids

2.4.1. Anacardic acid (1) from natural cashewnut-shell liquid (CNSL), Anacardium occidentale

The described method (Tyman et al., 1989) wasused with cashew nuts (400.0 g), from which by car-bon tetrachloride extraction, natural CNSL (91.08 g,32.6%) was recovered and thence by lead salt pre-cipitation, filtration and regeneration with cold dilutenitric acid and ethereal extraction, anacardic acidwas obtained as a viscous brown liquid (26.68 g,29.3%). Recoveries varied between 29 and 35%.Rf 0.56 (solvent B);νmax (film, cm−1), 3100, 1220(OH), 3010, 1610 (C=C), 1660 (C=O), 1380 (C–O);δH (CFT20, CCl4), 0.73–1.0 (CH3, unresolved t),1.17–1.63 [m, (CH2)n], 1.83–2.20 (CH2CH=CH,m), 2.6–3.06 [CH2Ar, CH2(CH=CH)2], 4.73–5.30(CH2=CH, CH=CH, m), 6.57–7.43 (HAr, m, 3H),11.23 (HO, HO2C, bs, 2H, D2O 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 Anacardiumgiganteum

The shells from the nut were cracked and the phe-nolic lipids extracted in the same way as describedfor the cashew. The shell liquid (6.71 g) in methylatedspirit (50 cm3) was added to lead hydroxide preparedfrom lead nitrate (3.81 g, 0.012 mol) and sodiumhydroxide (0.92 g, 0.023 mol) and the precipitatedred/brown solid filtered and washed with methylatedspirit (3 × 100 cm3). A suspension in methylatedspirit (100 cm3) was acidified with cold nitric acid toliberate anagigantic acid which was extracted withdiethyl ether. The combined extracts were washedwith saturated brine (7× 50 cm3), dried with mag-nesium sulphate and the solvent evaporated to give abrown solid (2.45 g, 36.5%) which was crystallised(light petroleum) to afford cream crystals (2.22 g,90.6%), mp, 75.5–76.6◦C; Rf 0.92 (solvent B);νmax(KBr disc, cm−1), 3350, 1220 (OH), 3050, 1310 (OH,carboxylic acid), 1650 (C=O), 1610 (C=C), 1380(C–O); δH (CCl4), 0.80–1.57 [(CH2)9, Me, m, 21H],2.70–3.07 (CH2Ar, t, 2H, J 8 Hz), 6.50–7.30 (HAr, 2dsuperimposed on dd,J 8 and 16 Hz), 10.30 (HOAr and


HO2C, bs, 2H, D2O exch.);m/z, M+ (%), 292.4 (9.1).C18H28O3 requires 292.4, 274.4 (3.9), M+–H2O.

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 follow-ing is dependent on the more selective hydroxymethy-lation and subsequent polymerisation of cardol,compared with cardanol. To technical CNSL (250.0 g,8.33 mol) in methanol (1000 cm3) at 45◦C, concen-trated HCl (20 cm3) was added to give pH 1, andthen 40% (w/v) methanolic formaldehyde solution(217.6 g, 7.25 mol) dropwise over 1 h. The mixturewas stirred and heated at 45–50◦C for 48 h afterwhich it was cooled, neutralised with 1 M sodiumhydroxide and concentrated in vacuo. The residue(305.0 g) in diethyl ether (500 cm3) was washed withsaturated brine (6× 500 cm3), dried with magnesiumsulphate, filtered and the solvent evaporated in vacuoto give a brown oil (303.65 g), vacuum distillationof which afforded cardanol as a clear yellow oil, bp190◦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); νmax (film, cm−1), 3350, 1170 (OH), 1590(C=C), 1370 (C–O), 700 (1,3-disubstituted ring);δH (CCl4), 0.73–1.0 (unresolved t, Me), 1.17–1.60[(CH2)n, m], 1.83–2.23 (CH2CH=CH, m), 2.30–2.90[CH2Ar, CH2(CH=CH)2], 4.73–5.70 (CH2=CH,CH=CH, m), 6.43–7.17 (HAr and HOAr, m, 5H, 1H,D2O 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), urushiolconstituents (Rf 0.63, 0.42, 0.29 and 0.27) and poly-meric material (Rf 0.11). Column chromatography ofJapanese lac (15.00 g) gave the following fractions,eluent, weight: 1–12, chloroform, 0.84 g; 13–48, chlo-roform:ethyl acetate (90:10), 9.75 g; residue on col-umn, diethyl ether, 4.21 g.

Urushiol was obtained from fractions 13–48 bydry flash chromatography with light petroleum(60–80◦C)/chloroform with gradient elution and fi-nally chloroform/ethyl acetate giving 9.15 g (61.0%on urushiol used);Rf 0.57 (solvent C);νmax (film,

cm−1), 3450, 1190, 3000, 1610, 1380;δH (CFT20,CDCl3), 0.82–1.00 (Me, unresolved t), 1.16–2.00 [m,(CH2)n, CH2CH=CH], 2.30–2.83 [m, CH2Ar andCH2(CH=CH)2], 4.83–6.16 (m, CH=CH and HAr),6.33(HOAr, s, 2H, D2O 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) fromcarboxylated technical CNSL

Isoanacardic acid was extracted from carboxy-lated technical CNSL, prepared as described (Durraniet al., 1980). The reaction product from carboxyla-tion (200.35 g) in methylated spirit (100 cm3) wasadded to lead hydroxide suspended in methylatedspirit (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 mix-ture was stirred for 30 min, the red brown solid wasfiltered, washed with methylated spirit and acidifiedwith cold dilute nitric acid to liberate the productwhich was extracted with diethyl ether (2× 100 cm3).The combined extracts were washed with saturatedbrine (2× 200 cm3), dried with magnesium sulphate,filtered and evaporated in vacuo to give a viscousbrown 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;νmax (film, cm−1),3150, 13,200, 1220 (OH), 3010, 1625 (C=C), 1660(C=O), 1390 (C–O) (phenol);δH (CCl4), 0.73–1.0(Me, unresolved t), 1.13–1.50 [(CH2)n, m], 1.87–2.23(CH2CH=CH, m), 2.40–2.87 [CH2Ar and CH2(CH=CH)2, m], 4.77–5.37 (CH2=CH and CH=CH,m) 6.53–6.80 (HAr, s superimposed on d,J 8 Hz, 2H),7.63–7.87 (HAr, d,J 8 Hz, 1H), 10.20–10.63 (HOArand HO2C, bs, 2H, D2O 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 fromphenolic lipid sources

2.5.1. Anacardic alcohol (5, n = 0)(2-hydroxymethyl-3-pentadecylphenol)

(i) (15:0)-Anacardic acid, prepared by catalytic hy-drogenation 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


(1.52 g, 0.04 mol) in dry THF (30 cm3) cooledto 0◦C under nitrogen, after which the mixturewas warmed to 50–55◦C for 7 h and then leftat ambient temperature for 16 h. Excess hydridewas decomposed by the addition of ethyl acetateand after the addition of dilute hydrochloric acid,the mixture was extracted with diethyl ether. Thecombined extracts were washed with saturatedbrine (5× 25 cm3) dried (magnesium sulphate),and concentrated in vacuo to yield a brown solidwhich was recrystallised (light petroleum) togive cream crystals (1.46 g, 53%), mp 63–65◦C,lit. (Gulati and Subba Rao, 1964), 65–66◦C;Rf 0.39 (solvent B);νmax (KBr, cm−1), 3500,1000 (primary OH), 3150, 1190 (OH, phenol),1590 (C=C), 1360, 1260 (C–O, phenol and pri-mary OH);δH (CDCl3), 0.83–1.53 [(CH2)13, Me,29H], 2.30–2.80 (CH2Ar, partially resolved t ands, HOCH2Ar, 3H, D2O exch.), 5.03 (ArCH2OH,s, 2H), 6.80–7.50 (HAr and HOAr, m, 4H, 1H,D2O exch.);m/z, M+ (%), 334 (18.5). C22H38O2requires 334.335 (4.4, M+ + 1).

(ii) Anacardic alcohol (Mehet, 1988) (5): reduc-tion of anacardic acid Anacardic acid (1)(43.54 g, 0.126 mol) was reduced in THF bythe same procedure as for the saturated com-pound with lithium aluminium hydride (14.32 g,0.189 mol). The crude product was purified bydry-column flash chromatography with gradi-ent elution to give5 as a viscous brown oil(33.04 g, 79.1%);Rf 0.38 (solvent B); νmax(liquid, cm−1), 3400, 1190, 1060 (OH), 1620(C=C), 1380 1270 (C–O, phenol and primaryOH); δH (CCl4), 0.73–0.97 (Me, unresolved t),1.1–1.50 [(CH2)n, m]1.77–2.17 (CH2CH=CH,m) 2.23–2.87 (CH2Ar and CH2(CH=CH)2, m),3.67–4.0 (HOCH2Ar, bs, 1H, D2O exch.), 4.67(HOCH2Ar, s, 2H), 4.77–5.07 (CH2=CH, m),5.07–5.50 (CH=CH, m), 6.17–6.90 (HAr andHOAr, m, D2O 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) con-taining anacardic acid (80%), cardol (15%) and 2-methylcardol/cardanol (5%) was reduced with LiAlH4(3.64 g, 0.096 mol) in THF and worked up as beforeto 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) topotassium hydroxide (1.38 g, 0.025 mol) in wa-ter (2 cm3) and ethanol (5 cm3) at 65◦C andcollected in diethyl ether (20 cm3) at 0◦C. Thissolution of diazomethane (0.6 g, 0.014 mol) indiethyl ether was then added to isoanacardicacid (1.38 g, 0.004 mol) in diethyl ether, untilthe solution was pale yellow and nitrogen evo-lution had ceased. Concentration of the mixtureand crystallisation of the residue from lightpetroleum gave cream needles (1.34 g, 93.1%),mp 45–46.5◦C; Rf 0.73 (solvent F). Found, C,76.16; H, 10.44. C23H38O3 requires C, 76.20;H, 10.57%; νmax (KBr, cm−1), 3180, 1220(OH), 1680 (C=O), 1620 (C=C), 1340, 1250(C–O); δH (CDCl3), 0.80–1.52 [(CH2)13, Me,m, 26H], 2.40–2.70 (CH2Ar, t, J 7 Hz, 2H), 3.90(MeO2CAr, s, 3H), 6.60–6.70 (HAr, d,J 8 Hz,1H), 7.21 (HAr, s, 1H), 7.62–7.72 (HAr, d,J8 Hz, 1H), 10.62 (HOAr, s, 1H, D2O 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 potas-sium carbonate (3.42 g, 0.025 mol) and dimethylsulphate (2.4 cm3, 0.025 mol) was refluxed for24 h. The cooled mixture was filtered and the fil-trate was washed with warm water (5× 25 cm3)to remove dimethyl sulphate, dried (magnesiumsulphate) and the solvent evaporated to givea cream solid which was recrystallised (lightpetroleum) to afford cream crystals (0.99 g,52.4%), mp 42–43.5◦C, identical spectroscopi-cally 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 tetrabutylam-monoum hydroxide (0.5 cm3) in water (20 cm3) and


dichloromethane (20 cm3) was vibromixed for 3 hwhen TLC (solvent M) indicated dimethylation wascomplete. The lower organic layer was separatedand washed with warm water (6× 50 cm3), driedand concentrated to give a cream solid which wascrystallised (light petroleum) to afford cream crystals(0.62 g, 58.5%), mp 29–31◦C; Rf 0.39 (solvent F).Found, C, 76.35; H, 10.89. C24H40O3 requires C,76.55; H, 10.71%;νmax (KBr, cm−1), 1690 (C=O),1600 (C=C), 1400, 1250, 1240 (C–O);δH (CCl4),0.67–1.23 [(CH2)13, Me, m, 29H], 2.27–2.5 (CH2Ar,t, J 7 Hz, 2H), 3.62 (MeO2CAr, s, 3H), 3.67 (MeOAr,s, 3H), 6.70–6.67 (HAr, s on d,J 8 Hz, 2H), 7.43–7.60(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 refluxed with1 M ethanolic KOH (3 cm3) for 1 h. The cooledmixture was then acidified with dilute hydrochlo-ric acid and the solid product collected, dried andcrystallised (light petroleum) to give white needles(0.45 g, 93.8%), mp 80.5–81.5◦C; Rf 0.24 (solventC). Found, C, 76.38; H, 10.45. C23H38O3 requiresC, 76.20; H, 10.57%;νmax (KBr, cm−1), 3230, 1340(OH), 1720 (C=O), 1610 (C=C), 1260 (C–O);δH(CCl4), 0.73–1.50 [(CH2)13, Me, m, 29H], 2.47–2.87(CH2Ar, t, J 7 Hz, 2H), 4.03 (MeO, s, 3H), 6.73–6.97(HAr, s on d,J 8 Hz, 2H), 7.67–8.43 (bs, s on d,J8 Hz, 2H, 1H, D2O exch.);m/z, M+ (%), 363.2 (81.4).

2.5.5. 2-Hydroxymethyl-5-pentadecylphenyl methylether (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 66.5–68◦C; Rf 0.66 (solvent C). Found, C, 79.46;H, 11.58. C23H40O2 requires C, 79.25; H, 11.57%;νmax (KBr, cm−1), 3340, 1050 (OH), 1520 (C=O),1270 (ArOMe), 1260 (C–O);δH (CCl4) 0.83–1.40[(CH2)n, Me, m, 29H], 2.0–2.67 (CH2Ar, HOCH2Ar,t on bs, 3H, 1H, D2O exch.), 3.80 (MeO, s, 3H), 4.47(HOCH2Ar, s, 2H), 6.50–6.70 (HAr, s on d,J 8 Hz,2H), 7.0–7.20 (HAr, d,J 8 Hz, 1H); m/z, M+ (%),348.4 (100), M+ + 1 349.6 (25.5).

Reduction of methyl 2-methoxy-4-pentadecylben-zoate (0.80 g, 0.002 mol) with lithium aluminiumhydride (0.23 g, 0.006 mol) similarly gave the sameproduct, as cream needles, mp 66.5–67.5◦C, Rf 0.66(solvent C) with similar spectroscopic data as for theproduct 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-pentadecyl-benzoic acid (1.00 g, 0.001 mol) in THF (20 cm3)was added dropwise under nitrogen to a sus-pension of lithium aluminium hydride (0.34 g,0.009 mol) in THF (10 cm3) cooled to 0◦C. Afterthe mixture had been refluxed for 2 h and then al-lowed to stand for 16 h, ethyl acetate (0.50 cm3)was added, followed by dilute hydrochloric acid.Ethereal extraction, washing of the combinedextracts with saturated brine, drying (magne-sium sulphate) and evaporation afforded a creamsolid which was recrystallised (light petroleum)to give pale cream crystals (0.56 g, 75.2%),mp 96–97◦C; Rf 0.37 (solvent C);νmax (KBr,cm−1), 3450, 1000 (OH, primary), 3180, 1220(OH, phenol), 1630 (C=C), 1380, 1290 (C–O);δH (CDCl3), 0.90–1.50 [(CH2)13, Me, m, 29H],2.17 (HOCH2Ar, s, 1H), 2.43–2.77 (CH2Ar, t, J7 Hz, 2H), 4.93 (ArCH2OH, s, 2H), 6.73–7.23(HAr, HOAr, m, 4H, 1H, D2O exch.);m/z, M+(%), 334.6 (34.9). C22H38O2 requires 334.5,M+ + 1 335.6 (8.4).

(ii) This compound was also prepared by reductionof the methyl ester.

2.5.7. Isoanacardic alcohol (9, R′ = H) (reductionof unsaturated methyl isoanacardate)

(i) By hydride reduction: Unsaturated 2-hydroxy-4-pentadecylbenzoic acid (4.00 g, 0.012 mol),was methylated with diazomethane (0.50 g,0.012 mol) in ethereal solution and the methylester obtained as a viscous brown oil (3.50 g,84.1%); Rf 0.35 (solvent N); νmax (liquid,cm−1), 3400, 1220 (OH), 3010, 1620 (C=C),1670 (C=O), 1350 (C–O);δH (CCl4) 0.83–1.03(unresolved t, Me) 1.13–1.57 [(CH2)n, m],1.77–2.27 (CH2CH=CH), 2.60–2.97 [CH2Ar,CH2 (CH=CH)2, m], 3.93 (MeO, s, 3H),


4.77–5.57 (CH2=CH, CH=CH, m), 6.47–7.30(HAr, m, 3H), 10.93 (HOAr, s, D2O 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) indry THF (60 cm3) was added dropwise, undernitrogen, to stirred lithium aluminium hydride(1.05 g, 0.027 mol) in dry THF (30 cm3) cooledto 0◦C. After refluxing for 2 h, the mixture wasworked up as for the saturated compound and pu-rified by chromatography on a silica column withlight petroleum (60–80◦C)/chloroform/ethyl ac-etate (gradient elution) to give a brown oil (2.56 g,88.6%);Rf 0.38 (solvent B);νmax (liquid, cm−1),3350, 1190, 1050 (OH), 1620 (C=C), 1390, 1280(C–O); δH (CCl4) 0.73–1.03 (unresolved t, Me),1.17–1.60 [(CH2)n, m], 1.80–2.20 (CH2CH=CH,m), 2.30–2.90 [CH2Ar, CH2(CH=CH)2, m],3.57–4.20 (HOCH2Ar, s, 1H, D2O exch.), 4.67(HOCH2Ar, s, 2H), 4.77–5.13 (CH2=CH, m),5.13–5.53 (CH=CH, m), 6.43–7.06 (HAr, m,3H), 7.30–8.10 (HOAr, s, 1H, D2O 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 hy-droxide (0.4 g, 10 mmol) in water (15 cm3) wasadded, followed by 37% aqueous formaldehyde(0.85 g, 10.5 mmol). After refluxing for 4 h,the mixture was cooled, diethyl ether (50 cm3)was added and the solution was acidified with3 M hydrochloric acid. The ethereal solutionwas washed with saturated brine, dried withmagnesium sulphate, filtered and concentratedin vacuo to give a golden oil (3.36 g). Thecrude product (0.85 g) was purified by prepara-tive TLC (solvent C) to give five bands (1)Rf0.64, 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 pentade-cylphenol, unsaturated isoanacardic alcohol, (3)Rf 0.15, 0.03 g (6.7%), which appears to be4-hydroxymethyl-5-mixed unsaturated pentade-cylphenol, (4) Rf 0.03, 0.06 g (12.2%), fromspectroscopy, 2,4-dihydroxymethyl-5-mixed un-saturated pentadecylphenol,m/z, 362.5, (5) base-line, probably polymer; for (band 2):νmax (film,cm−1), 3350, 1190, 1020 (OH), 1620 (C=C),

1370, 1270 (C–O, phenol and primary OH);δmax (CDCl3), 0.76–0.94 (Me, t), 1.17–1.36[(CH2)n, m], 1.57–2.04 (CH2 CH=CH, m),2.49–2.56 (CH2Ar, t, J 7 Hz, 2H), 2.60–2.78[CH2(CH=CH)2, m], 4.78 (HOCH2Ar, s, 2H),4.89–5.42 (CH2=CH, CH=CH, m), 6.64–6.69(HAr, s on d, 2H), 6.90–6.94 (HAr, d,J 8 Hz,1H); m/z, M+ (%), 332.6 (1.6), M+–H2O, 316.5(2.4), 314.5 (10.1), 312.5 (7.7), 310.5 (7.2).

(iii) By formylation of cardanol (Tyman, 1981)to8: Ethyl magnesium bromide prepared frombromoethane (3.8 cm3, 0.05 mol), in dry diethylether (30 cm3) and magnesium turnings (1.44 g,0.06 mol), in dry ether (20 cm3) was added to astirred solution of cardanol (15.35 g, 0.051 mol)in dry ether (100 cm3) at ambient tempera-ture. After completion of evolution of ethaneduring 16 h, and distillation of the ether, drybenzene was added, followed by paraformalde-hyde (5.98 g, 0.13 mol) and hexamethylphos-phoramide (8.8 cm3, 0.051 mol). The mixturewas stirred and refluxed for 6 h with moni-toring by TLC (solvent E). After cooling andacidification with dilute sulphuric acid, the mix-ture was extracted with diethyl ether (200 cm3),the ethereal extract was washed with saturatedbrine (5 × 150 cm3), dried with magnesiumsulphate, filtered and concentrated to afford anoil which was purified by column chromatog-raphy (light petroleum, 40–60◦C/diethyl ether,gradient elution) to give a golden oil (14.58 g,86.9%), 2-hydroxy-4-unsaturated pentadecyl-benzaldehyde;Rf 0.69 (solvent E);νmax (film,cm−1), 3200, 1200 (OH), 1660 (C=O), 1520(C=C), 1380 (C–O);δH (CCl4), 0.73–1.0 (Me, t),1.09–1.47[(CH2)n m], 1.7–2.17 (CH2CH=CH,m), 2.37–2.80 [CH2Ar and CH2(CH=CH)2, m],4.67–5.03 (CH2=CH, m), 5.06–5.37 (CH=CH,m), 6.50–6.70 (HAr, s on d,J 8 Hz, 2H),7.10–7.30 (HAr, d,J 8 Hz, 1H), 9.97 (ArCHO, s,1H), 10.77 (HOAr, s, D2O 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 vac-uum distillation rather than chromatographicallywere not successful due to polymerisation.

(iv) Borohydride reduction: The aldehyde (10.01 g,0.03 mol) in methanol (100 cm3) was cooled to0◦C and then treated with sodium borohydride


(2.30 g, 0.06 mol) in small portions while the tem-perature was maintained at 0◦C. The mixture wasallowed to warm to ambient temperature over16 h, monitored by TLC (solvent E) and uponcompletion of reduction, extracted with diethylether (200 cm3). The ethereal extract was washedwith dilute sulphuric acid (4×150 cm3), then withsaturated brine (5×150 cm3), dried with magne-sium sulphate, filtered and concentrated to givean oil which was purified by dry-column flashchromatography (chloroform/ethyl acetate withgradient elution) to afford a waxy solid (8.31 g,82.5%);Rf 0.37 (solvent B), identical chromato-graphically and spectroscopically with the prod-uct 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 re-ductions.

The reaction mixture was worked up as beforeand the crude product crystallised (light petroleum)to give 2-hydroxymethyl-3-undecylphenol as creamcrystals (0.48 g, 55.2%), mp 50.3–51.5◦C; Rf 0.28(solvent B);νmax (KBr, cm−1), 3500, 1000 (OH, pri-mary OH), 3180, 1210 (OH, phenol), 1620 (C=C),1380, 1260 (C–O);δH (CDCl3), 0.76–1.47 [(CH2)n,Me, m, 21H], 2.67–3.06 (CH2Ar, HOCH2Ar, s and t,1H, D2O exch.), 4.82 (HOCH2Ar, s, 2H), 6.50–7.40(HAr and HOAr, m, 4H, 1H, D2O exch.);m/z, M+(%), 278.1 (62.0). C18H30O2 requires 278.4, M+ + 1279.1 (10.1).

2.6. Synthesis of 1,3-diols from homologous3-alkylphenols by formylation and reduction of2-hydroxy-4-alkylbenzaldehydes

2.6.1. Synthesis of 3-alkylphenolsThis range of compounds was synthesised by the

Wittig reaction (Maercker, 1965)of 3-hydroxybenzal-dehyde and the appropriate alkylidenetriphenylphos-phoran, generated from the phosphonium salt withbutyllithium, to give the corresponding unsaturatedphenol which was hydrogenated to the required 3-alkylphenol. Formylation followed by sodium boro-hydride reduction afforded the 1,3-diol in the series ofhomologous 2-hydroxymethyl-4-alkylphenols.

The alkyltriphenylphosphonium bromide was pre-pared by refluxing the 1-bromoalkane (0.50 mol) andtriphenylphosphine (0.50 mol) ino-xylene (200 cm3)with monitoring by TLC (solvent G). Upon com-pletion of reaction the solvent was decanted fromthe cooled mixture and the product was washedwith 60–80◦C light petroleum (2× 200 cm3) andthe solvent removed in vacuo to yield the salt as aviscous oil. The stirred phosphonium salt (0.20 mol)in dry THF (200 cm3) under nitrogen was treatedwith a hexane solution of butyllithium (0.20 mol).3-Hydroxybenzaldehyde (0.20 mol) in dry THF(250 cm3) was then added to the phosphoran over30 min. The reaction mixture changed in colour fromwine-red to yellow and after removal of the solvent invacuo, the residual dark yellow viscous oil in etherealsolution was washed with aqueous sodium metabisul-phite (2× 200 cm3) to remove residual aldehyde. Theethereal solution was dried (magnesium sulphate), fil-tered, concentrated and the crude product purified bydry-column flash chromatography (chloroform/ethylacetate with gradient elution) to remove triph-enylphosphine oxide. The 1-(3-hydroxyphenyl)alk-1-ene (0.06 mol) in ethanol (200 cm3) was hydrogenatedin the presence of 5% palladium on charcoal (25% ofthe weight of alkene) at ambient pressure and tem-perature with TLC monitoring (solvent H). Removalof the catalyst by filtration and evaporation of thesolvent 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 triph-

enylphosphine (74.24 g, 0.28 mol) formedn-propyltri-phenylphosphonium bromide (104.20 g, 95.6%)which in THF was treated with a hexane solution ofn-butyllithium (230 cm3, 0.27 mol) and then with 3-hydroxybenzaldehyde (33.06 g, 0.27 mol) in THF. Thepurified product,1-(3-hydroxyphenyl)but-1-ene (17.9,44.7%), was obtained as a yellow oil;Rf 0.80 (solventH); νmax (film, cm−1), 3200 (OH), 1590 (C=C), 1300,970 (CH=CH); δmax 1-(3-hydroxyphenyl)but-1-ene(6.70 g, 0.045 mol) was hydrogenated in the presenceof 5% Pd–C (1.70 g) to give a light brown oil (6.47 g,95.8%) which showed a single band,Rf 0.81 (solventH, argentation TLC);νmax (film, cm−1), 3300, 1180(OH), 2850–2950 (CH), 1590 (C=C), 1490 (CH2def.); δH (CDCl3), 0.67–1.73 [(CH2)2, Me, m, 7H],2.30–2.67 (CH2Ar, t, J 7 Hz, 2H), 6.40–8.20 (HAr


and HOAr, m, with bs, 5H, 1H, D2O exch.);m/z, M+(%), 150.1 (29.3), M+ + 1, 151.1 (3.1), M+–CHEt,108.1 (100), M+ required for C10H14O, 150.2.

2.6.3. 3-n-Octylphenol (10, R1 = C8H17)1-Bromoheptane (21.48 g, 0.12 mol) and triph-

enylphosphine (31.44 g, 0.12 mol) formed the phos-phonium 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 3-hydroxybenzaldehyde (12.00 g, 0.10 mol), reactedby the general method, afforded, after purifica-tion by dry-column flash chromatography,1-(3-hydroxyphenyl)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% Pd–C(4.75 g) gave 3-n-octylphenol, as a golden oil (8.26 g,43.0%) showing one band by TLC,Rf 0.72 (solventH, argentation TLC);νmax (film, cm−1), 3350, 1180(OH), 2850–2950 (CH), 1590 (C=C), 1480 (CH2def.); δH (CDCl3), 0.67–1.73 [(CH2)6, Me, m, 15H],2.50 (CH2Ar, t, J 7 Hz, 2H), 5.57 (HOAr, bs, 1H,D2O exch.), 6.43–7.20 (HAr, m, 4H);m/z, M+ (%),206.1 (55.7). Required for C14H22O, 206.3, M+ + 1,207.1 (8.9), M+–C4H9, 149.1 (9.5), M+–C7H14,108.1 (70.2), M+–C7H15, 107.1 (18.1).

2.6.4. 3-n-Nonylphenol (10, R1 = C9H19)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-octyltriphen-ylphosphonium bromide (208.0 g, 88.25%). Thesalt (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 final purifi-cation by dry-column flash chromatography, gave1-(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% Pd–C (3.63 g)to afford a golden oil (11.56 g, 79.0%) showing a sin-gle band,Rf 0.71 (solvent A, argentation TLC);νmax(film, cm−1), 3200, 1170 (OH), 2850–2990 (CH),1590 (C=C), 1470 (CH2 def.); δH (CCl4), 0.67–1.73[(CH2)7, Me, m, 17H], 2.23–2.63 (CH2Ar, t, J 7 Hz,2H), 6.30–8.30 (HAr and HOAr, m and bs, 5H, 1H,

D2O exch.);m/z, M+ (%), 220.4 (11.1). Required forC15H24O, 220.3, M+ + 1, 221.4 (1.7), M+–C7H15,121.2 (8.6), M+–C8H16, 108.2 (100), M+–C8H17,107.2 (29.5).

2.6.5. 3-n-Undecylphenol (10, R1 = C11H23)By the general method, 1-bromodecane (60.00 g,

0.27 mol) with triphenylphosphine (71.26 g, 0.27 mol)formed the salt, n-decyltriphenylphosphoniumbromide (114.90 g, 87.5%). The salt (100.00 g,0.21 mol), n-butyllithium (138 cm3, 0.21 mol) and3-hydroxybenzaldehyde (25.01 g, 0.21 mol) afforded1-(3-hydroxyphenyl)undec-1-ene, purified as withthe 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, 0.07mol) was hydrogenated in the presence of 5% Pd–C(4.25 g) to give 3-n-undecylphenol as a yellow oil(10.95 g, 63.8%) having a single band by argenta-tion TLC, Rf 0.58 (solvent A);νmax (film, cm−1),3350, 1160 (OH), 2870–2980 (CH), 1600 (C=C),1490 (CH2 def.), 1380 (C–O);δH (CDCl3), 0.67–1.67[(CH2)9, Me, m, 21H], 2.33–2.67 (CH2Ar, t, J 7 Hz,2H), 6.50–7.90 (HAr and HOAr, m, 5H, 1H, D2Oexch.); m/z, M+ (%), 248.3 (5.5). Required forC17H28O, 248.4, M+ + 1, 249.3 (1.0), M+–C9H19121.1 (9.1), M+–C10H20, 108.1 (100), M+–C10H21,107.1 (32.3).

2.7. Synthesis of 2-hydroxy-, 3-alkyl-, 4-alkyl- and5-alkylbenzaldehydes by formylation of 2-, 3-, and4-alkylphenols, respectively

In a general method, ethyl magnesium bromideprepared from bromoethane (0.01 mol) in dry diethylether (10 cm3) and magnesium turnings (0.015 mol) indiethyl ether (10 cm3) was added to a stirred solutionof the alkylphenol (0.01 mol) in diethyl ether (20 cm3)and the mixture reacted at ambient temperature for16 h. After removal of the ether, dry benzene (50 cm3)was added to the phenoxymagnesium bromide, thenparaformaldehyde (0.025 mol) followed by hexam-ethylphosphoramide, HMPA (0.01 mol). The resultingmixture was refluxed for 4–6 h with monitoring byTLC (solvent E). The mixture was cooled, acidifiedwith dilute sulphuric acid, extracted with diethyl ether


(100 cm3), and the combined extracts washed withsaturated brine (4× 100 cm3), dried with magnesiumsulphate, and evaporated in vacuo to give the productwhich was purified by column chromatography.

By this methodology, aldehydes were synthe-sised from 2-n-nonylphenol, 3-n-butylphenol, 3-t-butylphenol, 2-(1,1,3,3-tetramethylbutyl)phenol, 3-n-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 bro-mide was prepared by the general method frombromoethane (1.5 cm3, 0.02 mol) magnesium turn-ings (0.60 g, 0.025 mol), and 3-n-butylphenol (3.00 g,0.02 mol). Paraformaldehyde (2.30 g, 0.05 mol) andHMPA (3.5 cm3) were added and reaction afforded theproduct which was purified by column chromatogra-phy on silica gel G (60–80◦C light petroleum/diethylether with gradient elution to give a yellow oil (1.81 g,50.8%);Rf 0.65 (solvent E);νmax (film, cm−1), 3200,1180 (OH), 1690 (C=O), 1590 (C=C), 1380 (C=O);δH (CCl4) 0.70–1.76 [(CH2)2, Me, m, 7H], 2.40–2.70(CH2Ar, t, J 7 Hz, 2H), 6.53–7.40 (HAr, m, 3H), 9.70(CHO, s, 1H), HOAr, s, 1H, D2O exch.);m/z, M+(%), 178.4 (39.7), M+ + 1, 179.4 (5.4). M+, requiredfor C11H14O2, 178.2.

2.7.2. 2-Hydroxy-4-t-butylbenzaldehyde(11, R1 = t-Bu)

3-t-Butylphenoxymagnesium bromide was pre-pared from bromoethane (5.3 cm3, 0.07 mol), magne-sium turnings (1.80 g, 0.075 mol) and 3-t-butylphenol(10.00 g, 0.07 mol). Formylation was effected withparaformaldehyde (7.71 g, 0.175 mol) and HMPA(11.7 cm3, 0.07 mol) and the crude product was puri-fied as before to afford a yellow oil (9.34 g, 78.7%);Rf 0.66 (solvent E);νmax (film, cm−1), 3200, 1190(OH), 1690 (C=O), 1620 (C=C), 1380 (C–O);δH(CCl4) 1.26 (Me3C, s, 9H), 6.77–7.33 (HAr, m, 3H),9.67 (CHO, s, 1H), 10.77 (HOAr, s, 1H, D2O exch.);m/z, M+ (%), 178.5 (49.3). Calculated for C11H14O2,178.2.

2.7.3. 2-Hydroxy-4-n-octylbenzaldehyde(11, R1 = C8H17)

3-n-Octylphenoxymagnesium bromide was pre-pared from bromoethane (1.0 cm3, 0.014 mol), magne-sium 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 purified asbefore to give a yellow oil (1.79 g, 53.6%);Rf 0.69(solvent E); νmax (film, cm−1), 3250, 1210 (OH),1690 (C=O), 1590 (C=C), 1380 (C–O);δH (CDCl3),0.72–1.47 [(CH2)6, Me, m, 15H], 2.40–2.73 (CH2Ar,t, J 7 Hz, 2H), 6.60–7.40 (HAr, m, 3H), 9.63 (CHO,s, 1H), 10.83 (HOAr, s, 1H, D2O exch.); m/z, M+(%), 234.3 (7.4), M+ + 1, 235.3 (1.3). Required forC15H22O2 234.3.

2.7.4. 2-Hydroxy-4-n-nonylbenzaldehyde(11, R1 = C9H19)

3-n-Nonylphenoxymagnesiumbromide obtainedfrom bromoethane (0.37 cm3, 0.005 mol) magnesiumturnings (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) andreacted to afford the crude product which was puri-fied by dry-column flash chromatography (40–60◦C,light petroleum/diethyl ether, with gradient elution),to give a yellow oil (0.61 g, 54.0%);Rf 0.72 (solventE); νmax (film, cm−1), 3300, 1220 (OH), 1680 (C=O),1580 (C=C), 1390 (C–O); δH (CCl4), 0.73–1.47[(CH2)7, Me, m, 17H], 2.3–2.63 (CH2Ar, t, J 7 Hz,2H), 6.57–7.17 (HAr, m, 3H), 9.57 (CHU, s, 1H),10.47 (OH, s, D2O exch.);m/z, M+ (%), 248.4 (30.9),M+ + 1 (249.4 (3.5). Required for C16H24O2, 248.4.

2.7.5. 2-Hydroxy-4-n-undecylbenzaldehyde(11, R1 = C11H23)

3-n-Undecyl phenoxy magnesium bromide wasprepared from bromoethane (1.0 cm3, 0.014 mol)magnesium turnings (0.46 g, 0.019 mol) and 3-n-undecylphenol (3.50 g, 0.014 mol). Treatment withparaformaldehyde (1.61 g, 0.035 mol) and HMPA(2.3 g, 0.014 mol) gave, upon reaction, the crude prod-uct which was recrystallised from light petroleum, togive cream needles (2.05 g, 52.7%);Rf 0.74 (solventE); νmax (film, cm−1), 3300, 1210 (OH), 1690 (C=O),1590 (C=C), 1390 (C–O); δH (CCl4), 0.83–1.37[(CH2)9, Me, m, 21H], 2.57 (CH2Ar, t, J 7 Hz,


2H), 6.67–7.47 (HAr, m, 3H), 9.83 (CHO, s, 1H),10.93 (HO, s, 1H, D2O exch.);m/z, M+ (%), 276.0(11.1), M+ + 1 277.0 (3.6). Required for C18H28O2,276.2.

2.8. 2-Alkylphenols

2.8.1. 2-n-Nonylphenol (13)In the same way as for 3-alkylphenols, 2-nonyl-

phenol was synthesised by the Wittig reaction.1-Bromooctane (50.00 g, 0.259 mol) and triphenyl-

phosphine (67.86 g, 0.259 mol) formedn-octyltriphen-ylphosphonium 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 purification bydry-column flash chromatography (60–80◦C, lightpetroleum/chloroform and gradient elution), a yellowoil, 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, 0.092mol) was hydrogenated in the presence of 10% Pd–C(2.50 g) to afford a yellow oil, 2-n-nonylphenol,showing, after purification, a single band (16.26 g,80.6%);Rf 0.55 (solvent A, argentation TLC);νmax(film, cm−1), 3400, 1170 (OH), 2850–2990 (CH),1600 (C=C), 1470 (CH2 def.), 1370 (C–O);δH(CDCl3) 0.70–1.50 [(CH2)7, Me, m, 17H], 1.77–2.27(CH2Ar, t, J 7 Hz, 2H), 6.30–7.93 (HAr and HOAr,m, 5H, 1H, D2O exch.);m/z, M+ (%), 220.4 (11.6).Required for C15H24O, 220.3, M+ + 1, 211.4(7.6).

2.8.2. 2-(1,1,3,3-Tetramethylbutyl)phenol (Laan andWard, 1987) (16)

To melted phenol (104.45 g, 1.11 mol) at 41◦C,aluminium turnings (1.04 g, 1%) were added. Hydro-gen evolution occurred and a rise in temperature to165◦C after which the mixture was cooled to 100◦Cand treated with 2,4,4-trimethylpent-1-ene (99.86 g,0.89 mol). The colour changed to red-brown and thetemperature was maintained at 100–110◦C duringTLC monitoring. After no further change the cooledmixture was diluted with water (50 cm3) and ex-tracted with chloroform (100 cm3). The extract waswashed with dilute sulphuric acid (3× 50 cm3), thenwith dilute NaOH (3× 50 cm3), dried, filtered andconcentrated in vacuo to give a viscous yellow oil, bp

88–100◦C/1.0 mmHg, which was crystallised (lightpetroleum) to afford white platelets, mp 38–40◦C(50.98 g, 27.7%);Rf 0.63 (solvent E);νmax (KBr disc,cm−1), 3540, 1190 (OH, phenol), 1610 (C=C), 1370(C–O), 760 (CH, 1,2-disubstituted ring);δH (CDCl3),0.77 (Me3CH2–, s, 9H), 1.43 (Me2CAr–, s, 6H),1.90 (CH2CMe2–, s, 2H), 4.67 (HOAr, s, 1H, D2Oexch.), 6.27–7.17 (HAr, m, 4H);m/z, M+ (%) 206.3(7.6), M+ + 1 207.3, 1.1). Calculated for C14H22O,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 pre-

pared from bromoethane (1.3 cm3, 0.017 mol),magnesium turnings (0.53 g, 0.022 mol), and 2-n-nonylphenol (3.80 g, 0.017 mol) and formylated byreaction with paraformaldehyde (1.95 g, 0.0425 mol)and HMPA (2.80 cm3, 0.017 mol) to give the productwhich was purified by dry-column flash chromatog-raphy (40–60◦C, light petroleum/diethyl ether withgradient elution), to give a yellow oil (1.80 g, 42.0%);Rf 0.68 (solvent E);νmax (film, cm−1), 3200, 1220(OH), 1690 (C=O), 1590 (C=C), 1390 (C–O);δH(CCl4), 0.67–1.53 [(CH2)7, Me, m, 17H], 1.93–2.27(CH2Ar, t, J 7 Hz, 2H) (HAr, m, 3H), 9.50 (CHO, s,1H), 11.1 (HOAr, s, 1H, D2O exch.);m/z, M+ (%),248.2 (3). Calculated for C16H24O2, 248.4.

2.9.2. 2-Hydroxy-3-(1,1,3,3-tetramethylbutyl)benzaldehyde (17)

2-(1,1,3,3-Tetramethylbutyl)phenoxymagnesiumbromide 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 ofparaformaldehyde (1.27 g, 0.027 mol) and HMPA(1.91 cm3, 0.011 mol) to give after reaction the prod-uct as a yellow oil (1.27 g, 55.9%), which was pu-rified as before;Rf 0.71 (solvent E);νmax (film,cm−1), 3400, 1250 (OH), 1710 (C=O), 1600 (C=C),1390 (C–O);δH (CCl4), 0.67 (Me3C, s, 9H), 1.37(Me2CAr–, s, 6H), 1.90 (CH2, s, 2H), 6.37–7.37(HAr, m, 3H), 9.50 (CHO, s, 1H), 11.53 (OH, s,1H, D2O exch.); m/z, M+ (%) 234.2 (4.3). Calcu-lated for C16H24O2, 248.4, 2-hydroxy-3-(1,1,3,3-tetramethylbutyl)phenol.


2.10. 2-Hydroxy-5-alkylbenzaldehtdes

2.10.1. 2-Hydroxy-5-t-butylbenzaldehyde(18, R = t-Bu)

4-t-Butylphenoxymagnesium bromide was pre-pared from bromoethane (4.9 cm3, 0.066 mol), magne-sium turnings (1.70 g, 0.071 mol) and 4-t-butylphenol(10.00 g, 0.066 mol). Formylation by reaction withparaformaldehyde (7.59 g, 0.165 mol) and HMPA(11.5 cm3, 0.066 mol) afforded the product whichwas purified by dry-column flash chromatography, asbefore, to give a yellow oil (9.90 g, 83.5%),Rf 0.75(solvent E); νmax (film, cm−1), 3200, 1180 (OH),1680 (C=O), 1590 (C=C), 1380 (C–O);δH (CCl4),1.23 (Me3C, s, 9H), 6.50–7.30 (HAr, m, 3H), 9.47(CHO, s, 1H), 10.37 (OH, s, D2O exch.);m/z, M+(%), 178.3 (22.8), M+ + 1 179.3 (3.0). Calculated forC11H14O2, 178.2.

2.10.2. 2-Hydroxy-5-(1,1,3,3-tetramethylbutyl)benzaldehyde (18, R = t-C8H17)

4-(1,1,3,3-Tetramethylbutyl)phenoxymagnesiumbromide was obtained from bromoethane (8.9 cm3,0.12 mol), magnesium turnings (3.00 g, 0.125 mol) and4-(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 purified onsilica gel G by column chromatography, to give ayellow oil (21.15 g, 74.5%),Rf 0.71 (solvent E);νmax (film, cm−1), 3200, 1190 (OH), 1680 (C=O),1590 (C=C), 1370 (C–O); δH (CCl4) (Me3C, s,9H), 1.23 (Me2CAr–, s, 6H), 1.57 (CH2, s, 2H),6.50–7.47 (HAr, m, 3H), 9.53 (CHO, s, 1H), 1.47(HO, s, 1H, D2O exch.);m/z, M+ (%), 234.5 (7.0),M+ + 1 235.5 (1.1). Calculated for C15H22O2,234.3.

2.10.3. 2-Hydroxy-5-n-nonylbenzaldehyde(18, R = n-C9H19)

4-n-Nonylphenoxy magnesium bromide was pre-pared from bromoethane (0.67 cm3, 0.009 mol),magnesium turnings (0.34 g, 0.014 pmol) and 4-nonylphenol (2.00 g, 0.009 mol) and formylated byreaction with paraformaldehyde (1.04 g, 0.023 mol)and HMPA (1.6 cm3, 0.009 mol). The crude productwas purified by dry-column flash chromatographyto give a yellow oil (1.86 g, 82.7%),Rf 0.73; νmax

(film, cm−1), 3300, 1210 (OH), 1680 (C=O), 1590(C=C), 1380 (C–O);δH (CCl4), 0.79–1.68 [(CH2)7,Me, m, 17H], 2.50–2.68 (CH2Ar, t, J 7 Hz, 2H),6.73–7.43 (HAr, m, 3H), 9.75 (CHO, s, 1H), 10.95(OH, s, 1H, D2O exch.);m/z, M+ (%), 248.4 (3.2),M+ + 1, 249.4 (3.9). Calculated for C16H24O2,248.4.

2.10.4. 2-Hydroxy-5-(3,5,5-trimethylhexyl)benzaldehyde (18, R = t-C9H19)

(i) 4-(3,5,5-Trimethylhexyl)phenoxymagnesiumbromide obtained from the reaction of bro-moethane (3.4 cm3, 0.045 mol), magnesiumturnings (1.20 g, 0.05 mol) and 4-(3,5,5-trimethyl-hexyl)phenol (10.00 g, 0.045 mol) was formy-lated by reaction with paraformaldehyde (5.18 g,0.09 mol) and HMPA (7.8 cm3, 0.045 mol). Thecrude product was purified by column chro-matography on silica gel G to give a pale yel-low oil (8.26 g, 73.3%),Rf 0.69 (solvent E);νmax (film, cm−1), 3200, 1180 (OH), 1680(C=O), 1590 (C=C), 1380 (C–O);δH (CCl4),0.67–2.20 (C9H19, m, 19H), 6.50–7.30 (HAr,M, 3H), 9.47 (CHO, s, 1H), 10.40 (OH, s,1H, D2O exch.); m/z, M+ (%), 248.3 (5.4),M+ + 1, 249.1 (1.3). Required for C16H24O2,248.4.

(ii) This compound was also obtained by the acidhydrolysis of the commercial reagent, Acorga (2-hydroxy-5-(3,5,5-trimethylhexyl)benzaldoxime).A 50:50 mixture of the oxime and nonylphenol(30.0 g) and 20% aqueous sulphuric acid wasstirred and warmed at 60–65◦C over 16 h, withmonitoring by TLC (solvent F). Upon comple-tion of reaction, the cooled mixture was extractedwith diethyl ether (200 cm3).

The ethereal extract was washed with saturatedbrine (4 × 100 cm3), dried (magnesium sulphate),concentrated and the residue purified dry-columnflash chromatography (light petroleum/diethyl etherwith gradient elution) to give 2-hydroxy-5-(3,5,5-trimethylhexyl)benzaldehyde as a yellow oil (11.20 g,79,2%) based on a 50% oxime/nonylphenol composi-tion. The product was chromatographically and spec-troscopically identical with the formylation product(18).


2.10.5. 2-Hydroxy-3-chloro-5-(1,1,3,3-tetramethylbutyl)benzaldehyde (20, R = t-C8H17)

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 over4 h (TLC monitoring, solvent J, to avoid dichlorina-tion). After completion of reaction, air was admitted toremove excess chlorine and the HCl formed. Concen-tration gave a yellow oil (16.80 g, 96.0%). 2-Chloro-4-(1,1,3,3-tetramethylbutyl)phenoxymagnesium bro-mide was formed from the addition of ethyl magne-sium bromide [prepared from bromoethane (8.72 cm3,0.08 mol), in diethyl ether (75 cm3) and magnesiumturnings (2.88 g, 0.12 mol) in diethyl ether (50 cm3)] to2-chloro-4-(1,1,3,3-tetramethylbutyl)phenol (19.46 g,0.08 mol) in diethyl ether (100 cm3) and the stirredreaction mixture was left at ambient temperaturefor 16 h, after which the ether was removed bydistillation 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 wasrefluxed for 6 h with TLC monitoring (solvent E).The cooled mixture was acidified with dilute sul-phuric acid, extracted with diethyl ether (200 cm3)and the ethereal extract was washed with saturatedbrine (5× 150 cm3), dried with magnesium sulphate,filtered and concentrated in vacuo to give the crudeproduct. This was purified by column chromatographyon silica gel G (chloroform/60–80◦C, light petroleumwith gradient elution). The product was obtained asa yellow oil (18.05 g, 83.1%);Rf 0.72 (solvent E);νmax (film, cm−1), 3420, 1180 (OH), 1670 (C=O),1610 (C=C), 1370 (C–O);δH (CCl4), 0.77 (Me3C, s,9H), 1.35 (CH2, s, 2H), 7.3,7.3 (HAr, 2s, 2H), 9.60(ArCHO, s, 1H), 10.83 (HOAr, s, 1H, D2O exch.);m/z, M+ (%), 268.2 (5.2), 270.2 (1.7).

2.11. Reduction of 2-hydroxy-3-, 4- and5-alkylbenzaldehydes

In a general method, a stirred solution of the alde-hyde (0.005 mol) in methanol (30 cm3), cooled tobelow 0◦C (ice–salt bath), was slowly treated withsodium borohydride (0.01 mol) while the reactiontemperature was kept below 0◦C. The reaction mix-ture was allowed to warm to ambient over 16 h andcompletion of reduction monitored by TLC (solventE). After the addition of diethyl ether (100 cm3), the

ethereal solution was washed with dilute sulphuricacid (4× 100 cm3), dried (magnesium sulphate) fil-tered and concentrated in vacuo to afford the crudeproduct which was purified either by column chro-matography or recrystallisation.

2.11.1. 2-Hydroxymethyl-5-n-butylphenol(12, R1 = n-Bu)

2-Hydroxy-4-n-butyl benzaldehyde (1.81 g, 0.01mol) and sodium borohydride (0.76 mol), by thegeneral method, gave the crude product which wasrecrystallised (60–80◦C light petroleum) to affordwhite needles, mp 66.7–67.6◦C (1.10 g, 60.1%);Rf0.15 (solvent C). Found, C, 73.29; H, 9.27. Requiredfor C11H16O, C, 73.30; H, 9.95%;νmax (KBr disc,cm−1), 3440, 1000 (OH, pr. alc.), 3180, 1250 (OH,phenol), 1620 (C=C), 1410, 1280 (C–O);δH (CDCl3),0.86–1.80 [(CH2)2, Me, m, 7H], 2.0–2.67 (CH2Ar,HOCH2, t on bs, 3H, D2O exch.), 4.80 (HOCH2Ar,s, 2H), 6.57–6.97 (HAr, m, 3H), 7.20 (HOAr, s, 1H,D2O exch.); m/z, M+ (%), 180.4 (18.4), M+ + 1,181.4 (2.1), M+–H2O, 162.4 (7.8).

2.11.2. 2-Hydroxymethyl-5-t-butylphenol(12, R1 = t-Bu)

By the general procedure, 2-hydroxy-4-t-butylben-zaldehyde (9.34 g, 0.05 mol) and sodium borohydride(3.97 g, 0.10 mol) afforded the crude product whichwas recrystallised (60–80◦C light petroleum/benzene)to give white fluffy crystals, mp 95.9–96.3◦C (6.51 g,68.9%); Rf 0.17 (solvent C). Found, C, 73.27; H,8.67. Required for C11H16O, C, 73.30; H, 8.95%;νmax(KBr disc, cm−1), 3350, 1000 (OH, pr. alc.), 3250,1210 (OH, phenol), 1590 (C=C), 1360, 1290 (C–O);δH (CDCl3) 1.27 (Me3C, s, 9H), 2.0 (HOCH2Ar, bs,1OH, D2O exch.), 4.80 (HOCH2Ar, s, 2H), 6.83–7.06(HAr, m, 3H), 7.17 (HOAr, s, 1H, D2O 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-C8H17)

2-Hydroxy-4-n-benzaldehyde (0.93 g, 0.004 mol)and sodium borohydride (0.30 g, 0.008 mol) gave thecrude product which was crystallised (40–60◦C lightpetroleum/diethyl ether) to give white needles, mp85.8–86.6◦C (0.50 g, 53.2%);Rf 0.22 (solvent C).Found, C, 76.38; H, 9.95. Required for C15H24O, C,76.23; H, 10.24%;νmax (KBr disc, cm−1), 3440, 1000


(OH, pr. alc.), 3240, 1210 (OH, phenol), 1600 (C=C),1390, 1280;δH (CDCl3), 0.86–1.53 [(CH2)6, Me, m,15H], 2.13 (CH2Ar, t, J 7 Hz, 2H), 2.50 (HOCH2, bs,1H, D2O exch.), 4.70 (HOCH2Ar, s, 2H), 6.63–7.17(HAr, HO, m, 4H, 1H, D2O exch.); m/z, M+ (%),235.9 (8.2), M+–H2O, 218.0 (5.2).

2.11.4. 2-Hydroxymethyl-5-n-nonylphenol(12, R1 = n-C9H19)

2-Hydroxy-4-n-nonyl benzaldehyde (1.86 g, 0.007mol) and sodium borohydride (0.57 g, 0.014 mol) af-forded the crude product which was recrystallised asfor the octyl compound to give white needles, mp88.7–89.1◦C (1.53 g, 81.8%);Rf 0.35 (solvent E).Found, C, 76.77; H, 10.38. Required for C14H26O,C, 76.77; H, 10.47%;νmax (KBr disc, cm−1), 3440,1000 (OH, pr. alc.), 3180, 1220 (OH, phenol), 1595(C=C), 1410, 1280 (C–O);δH (CDCl3) 0.87–1.45[(CH2)7, Me, m, 17H], 1.56 (HOCH2Ar, bs, 1H),2.44–2.62 (CH2Ar, t, J 7 Hz, 2H), 4.77 (HOCH2Ar, s,2H), 6.59–7.21 (HAr, HOAr, m, 4H, 1H, D2O exch.);m/z, M+ (%), 250.1 (16.4), M+ + 1, 251.1 (2.1),M+–H2O, 232.0 (8.9).

2.11.5. 2-Hydroxymethyl-5-n-undecylphenol(12, R1 = n-C11H23)

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 ob-tain white needles, mp 90.4–91.4◦C (1.42 g, 68.9%);Rf 0.22 (solvent C). Found, C, 77.84; H, 10.86. Re-quired for C18H30O, C, 77.66; H, 10.86%;νmax (KBrdisc, cm−1), 3450, 1000 (OH, pr. alc.), 3060, 1210(OH, phenol), 1590 (C=C), 1410, 1260 (C–O);δH(CDCl3) 0.87–1.74 [(CH2)9, Me, m, 21H], 2.34–2.61(CH2Ar, HOCH2, t on bs, 3H, 1H, D2O exch.), 4.76(HOCH2Ar, s, 2H), 6.57–7.10 (HAr HOAr, m, 4H,1H, D2O 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-C9H19)

2-Hydroxy-3-n-nonylbenzaldehyde (1.17 g, 0.005mol) and sodium borohydride (0.38 g, 0.01 mol) werereacted by the general method and the crude productpurified by dry-column flash chromatography to givea pale yellow oil (0.91 g, 77.1%),Rf 0.50 (solvent E).Found, C, 76.87; H, 9.93. Required for C16H26O2,

C, 76.75; H, 10.47%;νmax (film, cm−1), 3350 (OH),1220, 1020 (OH, phenol, pr. alc.), 1600 (C=C), 1380,1260 (C–O);δH (CDCl3), 0.83–1.45 [(CH2)7, Me, m,17H], 2.15–2.23 (CH2Ar, t, J 7 Hz, 2H), 2.25 (HO,s, HOCH2Ar, D2O exch.), 4.77 (HOCH2Ar, s, 2H),6.07–7.33 (HAr, m, 3H), 7.52 (HOAr, s, 1H, D2Oexch.); m/z, M+ (%), 250.2 (20.3), M+ + 1, 251.2(3.4), M+–H2O, 232.2 (18.0).

2.11.7. 2-Hydroxymethyl-6-(1,1,3,3-tetramethylbutyl)phenol (15, R1 = t-C8H17)

2-Hydroxy-3-(1,1,3,3-tetramethylbutyl)benzaldeh-yde (0.94 g, 0.004 mol), and sodium borohydride(0.30 g, 0.008 mol) gave the crude product which waspurified by dry-column flash chromatography (lightpetroleum, diethyl ether with gradient elution) to givewhite needles, mp 74.1–75.1◦C (0.65 g, 68.7%),Rf0.64 (solvent E). Found, C, 76.22; H, 10.52. Re-quired for C15H24O, C, 76.23; H, 10.24%;νmax (KBrdisc, cm−1), 3400, 1090 (OH, pr. alc), 3180, 1250(OH, phenol), 1620 (C=C), 1410, 1280 (C–O, phenoland pr. alc.);δH (CCl4), 0.73 [ArCMe2CH2C(Me)3,s, 9H], 1.40 (ArCMe2, s, 6H), 1.87 (HOCH2Ar, s,1H, D2O exch.), 1.93 (ArCMe2CH2, s, 2H), 4.67(HOCH2Ar, s, 2H), 6.47–7.07 (HAr, m, 3H), 7.40(HOAr, s, 1H, D2O 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, 0.055mol) and sodium borohydride (4.16 g, 0.10 mol) gavethe crude product which was recrystallised to givewhite needles, mp 85.3–86.1◦C (6.71 g, 67.6%);Rf0.26 (solvent E). Found, C, 73.05; H, 8.70. Requiredfor C11H16O, C, 73.30; H, 8.95%;νmax (KBr disc,cm−1), 3350, 1000 (OH, pr. alc.), 3250, 1200 (OH,phenol), 1590 (C=C), 1380, 1290 (C–O);δH (CDCl3),1.23 (Me3C, s, 9H), 2.0–2.23 (HOCH2Ar, bs, 1H, D2Oexch.), 4.63 (HOCH2Ar, s, 2H), 6.47–7.03 (HAr andHOAr, m, 4H, 1H, D2O exch.);m/z, M+ (%), 180.3(19.6), M+ + 1, 181.3 (2.0), M+–H2O, 162.3 (21.5).

2.11.9. 2-Hydroxymethyl-4-(1,1,3,3-tetramethylbutyl)phenol (19, R = t-C8H17)

2-Hydroxy-5-(1,1,3,3-tetramethyl)benzaldehyde(15.46 g, 0.066 mol) with sodium borohydride (4.91 g,


0.13 mol) gave the crude product which was recrys-tallised (40–60◦C light petroleum/diethyl ether) to af-ford white crystals, mp 83.5–84.4◦C (12.73, 81.6%);Rf 0.20 (solvent E);νmax (KBr disc, cm−1), 3530,1000 (OH, pr. alc.), 3260, 1180 (OH, phenol), 1610(C=C), 1380, 1270 (C–O);δH (CCl4), 0.70 (Me3C,s, 9H), 1.27 (–Me2CAr, s, 6H), 1.60 (–CH2Me2CAr,s, 2H), 3.27 (HOCH2Ar, bs, 1H, D2O exch.), 4.57(HOCH2Ar, s, 2H), 6.43–7.0 (HAr, m, 3H), 7.33(HOAr, bs, 1H, D2O exch.). Found, M+, 236.1777.Required for C15H24O, 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-C9H19)

2-Hydroxy-5-n-nonylbenzaldehyde (0.61 g, 0.002mol) and sodium borohydride (0.18 g, 0.004 mol) af-forded the crude product which was recrystallised(40–60◦C, light petroleum/diethyl ether) to givewhite platelets, mp 97.4–97.9◦C (0.35 g, 57.4%);Rf0.27 (solvent E). Found, C, 76.88; H, 10.68. Requiredfor C16H26O, C, 76.75; H, 10.47%;νmax (KBr disc,cm−1), 3440, 1130 (OH, pr. alc.), 3170, 1220 (OH,phenol), 1595 (C=C), 1390, 1280 (C–O);δH (CDCl3),0.77–1.67 [(CH2)7, Me, m, 17H], 1.83 (HOCH2Ar,s, 1H, D2O exch.), 2.23–2.53 (CH2Ar, t, J 7 Hz, 2H),4.63 (HOCH2Ar, s, 2H), 6.47–6.93 (HO and HOAr,4H, 1H, D2O exch.); m/z, M+ (%), 250.1 (30.8),M+ + 1, 251.1 (3.9), M+–H2O, 232.1 (22.4).

2.11.11. 2-Hydroxymethyl-4-(3,5,5-trimethylhexyl)phenol (19: R = t-C9H19)

(i) From reduction: 2-Hydroxy-5-(3,5,5-trimethy-lhexyl)benzaldehyde (11.20 g, 0.045 mol) re-acted with sodium borohydride (3.80 g, 0.90 mol)afforded the crude product which was puri-fied by dry-column flash chromatography (lightpetroleum/diethyl ether with gradient elution)to give a pale yellow oil (8.13 g, 63.7%);Rf0.32 (solvent E);νmax (film, cm−1), 3350 (OH),1190 (OH, phenol), 1010 (OH, pr. alc.), 1260(C=C), 1390, 1620 (C–O);δH (CDCl3), 0.43–1.83(C9H19, m, 19H), 2.63 (HOCH2Ar, bs, 1H, D2Oexch.), 4.77 (HOCH2Ar, s, 2H), 6.60–7.23 (HArand HOAr, m, 4H, 1H, D2O exch.);m/z, M+ (%),250.1 (9.5), M+ + 1, 251.1 (1.2). Found, M+,250.1934. Required for C16H26O, 250.1933.

(ii) From hydroxymethylation: To 4-(3,5,5-trimethyl-hexyl)phenol (11.44 g, 0.052 mol), stirred andheated to 60◦C, 3 M sodium hydroxide (1 cm3)was added, to raise the pH to 10–11, and then37% aqueous formaldehyde (5.4 cm3, 0.067 mol)The reaction mixture was stirred and heatedfor 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), filtered and con-centrated to give the crude product which waspurified by dry-column flash chromatography(40–60◦C, light petroleum/diethyl ether with gra-dient elution) to afford a pale yellow oil (3.90 g,30.0%) consisting of 2-hydroxymethyl-4-(3,5,5-trimethylhexyl)phenol;Rf 0.29 (solvent C);νmax(film, cm−1), 3350 (OH), 1620 (C=C), 1390,1260 (C–O);δH (CCl4), 0.37–1.57 (C9H19, m,19H), 3.10–3.87 (HOCH2Ar, bs, 1H, D2O exch.),4.50 (HOCH2Ar, s, 2H), 6.33–6.93 (HAr andHOAr, m, 4H, 1H, D2O exch.); m/z, M+ (%),250.4 (19.8), M+ + 1, 251.4 (3.2). Calculated forC16H26O2, 250.1933. Found, 250.1932.

2.11.12. 2-Hydroxymethyl-6-chloro-4-(1,1,3,3-tetramethylbutyl)phenol (21, R = t-C8H19)

2-Hydroxy-3-chloro-5-(1,1,3,3-tetramethylbutyl)benzaldehyde (9.42 g, 0.035 mol) and sodium boro-hydride (2.65 g, 0.07 mol), by the general method, af-forded (TLC monitoring, solvent E) the crude productwhich was purified by dry-column flash chromatog-raphy to give a pale yellow oil (7.34 g, 77.3%);Rf0.35 (solvent E);νmax (film, cm−1), 3340 (OH), 1610(C=C), 1370, 1260 (C–O), 1180, 1020 (OH, pr. alc.);δH (CDCl3) 0.73 (Me3C, s, 9H), 1.27 (Me2C–, s,6H), 1.62 (CH2CMe2C–, s, 2H), 3.53 (HOCH2Ar, s,1H, D2O exch.), 4.60 (HOCH2Ar, s, 2H), 6.88–7.05(HAr and HOAr, 3s, 3H, 1H, D2O exch.);m/z, M+(%), 270.3 (13.0), 272.4 (4.2). Found, M+, 270.1389.Calculated for C15H23O2Cl, 270.1386.

2.12. Synthesis of 2-hydroxymethyl-3-n-alkylphenolsfrom ethyl 2-methoxy-6-alkylbenzoates

2.12.1. Ethyl 2-methoxy-6-alkylbenzoates (22)To lithium diisopropylamide (LDA), prepared

from diisopropylamine (0.14 mol) andn-butyllithium(0.12 mol) in dry THF (40 cm3), under nitrogen, ethyl


2-methoxy-6-methylbenzoate (0.1 mol) in dry THF(60 cm3) was added at−70◦C. After reaction to com-plete 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 leftfor 4 h and then allowed to warm to ambient temper-ature. To the now golden-brown solution, methylatedspirit (60 cm3) was added and after stirring for 6 h, themixture was acidified with excess 3 M sulphuric acidand extracted with diethyl ether (2× 200 cm3) fol-lowed by ethyl acetate (2× 200 cm3). The combinedextracts were washed with saturated sodium hydrogencarbonate (2× 200 cm3), then with saturated brine(4 × 200 cm3), dried (magnesium sulphate), filteredand the filtrate concentrated to afford the crude prod-uct which was purified by column chromatography.

2.12.2. Ethyl 2-hydroxy-6-n-alkylbenzoates (23)(ethyl 6-n-alkylsalicylates)

The alkylmethoxy derivatives (0.01 mol) in drydichloromethane (50 cm3) were demethylated at−78◦C with boron tribromide (0.02 mol) in dichlo-romethane (20 cm3) and the mixture then allowedto warm to ambient temperature over 16 h. The ex-cess reagent was hydrolysed with water (25 cm3)and the phenolic product extracted with diethyl ether(100 cm3). The ethereal extract was washed with sat-urated brine (3× 100 cm3) until neutral, dried withmagnesium sulphate, filtered and the solvent evap-orated in vacuo. The crude product was purified bycolumn chromatography.

2.12.3. 2-Hydroxymethyl-3-n-alkylphenols (24)Ethyl 2-hydroxy-6-methylbenzoate and ethyl 2-

methoxy-6-methylbenzoate were prepared as de-scribed (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, 0.02mol) and 1-bromopropane (2.4 cm3) gave the crudeproduct which was purified by dry-column flash chro-matography to give a golden oil (3.24 g, 66.5%);Rf0.33 (solvent F);νmax (film, cm−1), 1730 (C=O),1600 (C=C), 1270, 1250 (C–O);δH (CCl4), 0.83–1.37[(CH2)2, 2Me, m, 10H], 2.26–2.50 (CH2Ar, t, J 7 Hz,2H), 3.6 (OMe, s, 3H), 3.9–4.26 (OCH2, q, J 7 Hz,

2H), 6.3–6.96 (HAr, m, 3H);m/z, M+ (%), 236.2(38.9), M+ + 1, 237.2 (6.3). Required for C14H20O3,236.3.

Demethylation afforded a crude product which waspurified by dry-column flash chromatography to give agolden brown oil (1.49 g, 58.7%), ethyl 2-hydroxy-6-n-butylbenzoate and a solid (white needles from 40 to60◦C, light petroleum), 2-hydroxy-6-n-butylbenzoicacid, mp 114.2–115.0◦C (0.51 g, 23.0%); for the es-ter, Rf 0.49 (solvent F);νmax (film, cm−1), 3400,1220 (OH), 1650 (C=O), 1600 (C=C); δH (CDCl3),0.53–1.70 [(CH2)2, 2Me, 10H], 2.25–2.90 (CH2Ar, t, J7 Hz, 2H), 4.10–4.47 (OCH2, q,J 7 Hz, 2H), 6.35–7.20(HAr, m, 3H), 11.20 (HOAr, s, 1H, D2O exch.);m/z,M+ (%), 222.2 (34.5), M+ + 1, 223.3 (6.4). Requiredfor C13H18O3, 222.3; for the acid,Rf 0.01 (solventF); νmax (KBr disc, cm−1), 3400, 1220 (OH), 2600,1600 (OH, acid with internal H-bonding), 1650 (C=O),1440, 1310 (C–O);δH (CCl4), 0.50–1.77 [(CH2)2, Me,m, 7H], 2.53–2.93(CH2Ar, t, J 7 Hz, 2H), 6.23–7.10(HAr, m, 3H), 10.87 (OH, HO2C, s, 2H, D2O exch.);m/z, M+ (%), 194.1 (33.7), M+ + 1, 195.1 (4.4). Re-quired for C11H14O3, 194.2.

2.12.5. Ethyl 2-hydroxy-6-n-octylbenzoate(23, R = n-C7H15)

By the general procedure, ethyl 2-methoxy-6-meth-ylbenzoate (8.00 g, 0.041 mol) and 1-bromoheptane(8.2 cm3, 0.052 mol) reacted to give the crude productwhich was purified by dry-column flash chromatogra-phy to give a golden oil (5.93 g, 49.25%);νmax (film,cm−1), 1730 (C=O), 1600 (C=C), 126-, 1250 (C=O,ether and ester);δH (CDCl3), 0.79–1.67 [(CH2)6,2Me, m, 18H], 2.27–2.76 (CH2Ar, t, J 7 Hz, 2H),3.76 (MeO, s, 3H), 4.22–4.49 (OCH2, q, J 7 Hz, 2H),6.64–7.30 (HAr, m, 3H);m/z, M+ (%), 292.1 (18.1),M+ +1, 293.1 (2.7), M+–OEt, 247.0 (24.7). Requiredfor C18H28O3, 292.2.

Demethylation gave a cream coloured solid whichwas purified by dry-column flash chromatography(60–80◦C, light petroleum/chloroform with gradi-ent elution to afford a yellow oil (3.10 g, 54.9%)consisting of 2-hydroxy-6-n-octylbenzoate and 2-hydroxy-6-n-octylbenzoic acid, mp 92.4–93.6◦C(1.57 g, 30.9%); for the ester,Rf 0.44 (solvent F);νmax(film, cm−1), 3400, 1220 (OH), 1650 (C=O), 1600(C=C), 1320, 1250 (C–O);δH (CDCl3), 0.80–1.63


[(CH2)6, 2Me, m, 18H], 2.53–2.97 (CH2Ar, t, J 7 Hz,2H), 4.27–4.54 (OCH2, q, 2H), 6.50–7.33 (HAr,m, 3H), 11.13 (HOAr, s, 1H, D2O exch.);m/z, M+(%), 278.2 (17.9), M+–OEt, 232.2 (21.4). Requiredfor C17H26O3, 278.4; for the acid,Rf 0.04 (sol-vent F); νmax (KBr disc, cm−1), 3400, 1220 (OH),2600, 1610 (OH, acid H-bonding), 1650 (C=O), 1600(C=C), 1440, 1310 (C–O);δH (CDCl3), 0.87–1.68[(CH2)6, Me, m, 15H], 2.87–3.05 (CH2Ar, t, J 7 Hz,2H), 6.68–7.42 (HAr, m, 3H), 9.75–12.75 (HOArand HO2C, 2H, D2O exch.); m/z, M+ (%), 250.2(33.1), M+ + 1, 251.1 (4.6). Required for C15H22O3,250.3.

2.13. Reduction of ethyl 6-n-alkylsalicylates to2-hydroxymethyl-3-n-alkylphenols (24)

General method: The ethyl 2-hydroxy-6-n-alkylbenzoate (0.01 mol) in dry THF (30 cm3) wastreated with an ice-cold suspension of lithium alu-minium hydride (0.03 mol) in dry THF (20 cm3)under nitrogen. After completion of reaction (TLCmonitoring) the excess reagent was destroyed withethyl acetate (ca. 1 cm3), the mixture was then acid-ified with 3 M HCl and extracted with diethyl ether(100 cm3). The extract was washed with saturatedbrine until neutral, dried (anhydrous sodium sulphate),filtered and concentrated to give a crude productwhich was purified by dry-column flash chromatogra-phy. The method was also used for the correspondingacid.

2.13.1. 2-Hydroxymethyl-3-methylphenol(24, R = H)

By the general method ethyl 2-hydroxy-6-methylbenzoate (1.70 g, 0.009 mol) and lithium alu-minium hydride (1.02 g, 0.027 mol) gave a crudeproduct which was recrystallised (light petroleum)to yield white crystals, mp 105.6–106.6◦C (0.73 g,56.1%); Rf 0.23 (solvent C). Found, C, 69.25; H,7.22. Calculated for C8H10O3, C, 69.55; H, 7.10%;νmax (KBr disc, cm−1), 3300 (OH), 1210, 1040 (OH,phenol and pr. alc.), 1600 (C=C), 1330, 1290 (C–O);δH (CDCl3), 2.20 (MeAr, s, 3H), 2.45 (HOCH2Ar, bs,1H, D2O exch.), 4.75 (HOCH2Ar, s, 2H), 6.33–7.03(HAr, m, 3H), 7.45 (HOAr, bs, 1H, D2O exch.);m/z,M+ (%), 138.1 (46.2), M++1, 139.1 (4.3), M+–H2O,120.0 (63.4).

2.13.2. 2-Hydroxymethyl-3-n-butylphenol(24, R = n-Pr)

By the general method, ethyl 2-hydroxy-6-n-butylbenzoate (1.91 g, 0.009 mol) and LAH (0.29 g,0.03 mol) afforded the crude product. Similarly, 2-hydroxy-6-n-butylbenzoic acid (0.51 g, 0.003 mol)and LAH (0.98 g, 0.009 mol) gave the same prod-uct which was purified by dry-column flash chro-matography (chloroform/ethyl acetate, with gradientelution) to give white crystals (from 40 to 60◦C,light petroleum), mp 54.9–55.7◦C (1.59 g, 96.5%);Rf 0.29 (solvent C). Found, C, 73.05; H, 8.70. Re-quired for C11H16O2, C, 73.30; H, 8.95%;νmax (KBrdisc, cm−1), 3300 (OH), 1210, 1030 (OH, phenoland pr. alc.), 1600 (C=C), 1345, 1290 (C–O);δH(CDCl3), [(CH2)2, Me, m, 7H], 2.09–2.73 (CH2Ar, t,J 7 Hz, 2H), 2.63–4.0 (HOCH2Ar, s, 1H, D2O exch.),4.53–4.77 (HOCH2Ar, s, 2H), 6.27–7.03 (HAr andHOAr, m, 4H, 1H, D2O exch.);m/z, M+ (%), 180.1(82.9), M+ + 1, 181.0 (9.4), M+–H2O, 162.0 (49.3).

2.13.3. 2-Hydroxymethyl-3-n-octylphenol(24, R = n-C7H15)

By the general procedure, ethyl 2-hydroxy-6-n-octylbenzoate (3.10 g, 0.011 mol) and LAH (1.25 g,0.033 mol), and similarly 2-hydroxy-6-n-octylbenzoicacid (1.57 g, 0.006 mol) and LAH 0.68 g, 0.018 mol)together gave the crude product. Purification by dry-column flash chromatography gave a clear viscousoil (combined batches, 2.79 g, 67.9%);Rf 0.31 (sol-vent C). Found, C, 76.08; H, 10.54. Required forC15H24O2, C, 76.23; H, 10.24%;νmax (KBr disc,cm−1), 3300 (D2O); m/z, M+ (%), 236.1 (26.1),M+ + 1, 237.1 (3.7), M+–H2O, 218.2 (9.2) (OH),1190, 1040 (OH, phenol and pr. alc.), 1590 (C=C),1350, 1250 (C–O);δH (CDCl3), [(CH2)6, Me, m,15H], 2.44–2.62 (CH2Ar and HOCH2Ar, t, J 7 Hz,2H and 1H, D2O exch.), 4.85 (HOCH2Ar, s, 2H),6.60–7.20 (HAr and HOAr, m, 4H, 1H exch.).

3. Results and discussion

3.1. Sources of phenolic lipids

The phenolic lipids (Fig. 1), from Anacardiaceaesources all require purification before semi-syntheticusage (Tyman, 1995). Of the variety of methods avail-able, the process of phase separation (Tyman et al.,


1992) is applicable to both the isolation of anacardicacid and of cardanol, respectively, from natural andtechnical CNSL since it is essentially a mild ambienttemperature method in which the highly unsaturatedconstituents are preserved intact. Additionally, theremaining component, namely cardol, is also simul-taneously recoverable whereas in chemical or purelythermal methods it is lost. Technical CNSL is avail-able commercially but with natural CNSL, althoughthe technology exists to cut shells, while leaving theedible nut uncontaminated, the subsequent solvent ex-traction stage, or high pressure extrusion, has not yetbeen achieved on a commercial scale (M. Grimminger,Buhler-Miag Co., private communication). In a similarway, urushiol is processed in Japan and China but notgenerally available elsewhere. Thitsiol, the 4-alkenylanalogue (Tyman, 1973, 1979) of the 3-alkenyl-1,2-diol, urushiol, was unfortunately not available forstudy as a borate complexant in the present work.

However, although synthesis of all the constituentsof these phenolic lipids has been achieved (Kozubekand Tyman, 1999; Tyman, 2001; Niimura et al., 1998),natural sources remain the source of supply.

As well as the natural aromatic diols and semi-synthetico-hydroxymethylols described in the presentstudy, the unsaturated side chains of methylated phe-nolic lipids have been polyhydroxylated (Durraniet al., 1982) to afford potential borate complexants.

3.2. Synthesis of 1,3-diols (2-hydroxymethylols)

TheSchemes 1–6depict the essence of the presentwork namely to semi-synthesise and synthesise ho-mologous 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 tocompare their relative borate complexation.

3.3. Anacardic alcohols, 2-hydroxymethyl-3-alk(en)ylphenols

Lithium aluminium hydride reduction of C11, anagi-gantic and C15, anacardic acids (2) and (1), affordedthe corresponding anacardic alcohols (6) and (5, n =0, 2, 4, 6), respectively, as shown inScheme 1.

Generally, the use of methyl esters afforded slightlybetter 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 esterification, either by the lessattractive use of diazomethane, or more convenientlyby esterification, offset this slight gain.

3.4. Homologous 2-hydroxymethyl-3-alkylphenols

Homologous 2- hydroxymethyl- 3- alkylphenolswere synthesised as shown inScheme 2. Alkylation(Tyman and Visani, 1997; Carpenter et al., 1984)of ethyl 2-methoxy-6-methylbenzoate (Hauser andPogany, 1980) afforded the required 6-alkyl deriva-tive which was demethylated with boron tribromide(Durrani and Tyman, 1980) to give the correspondingsalicylate. Reduction with lithium aluminium hydridefurnished the methylol.

Certain of the homologous 2-hydroxymethyl-3-alkylphenols (24, R = H, n-C3H7 andn-C7H15) weresynthesised by the alkylation of ethyl 2-methoxy-6-methylbenzoate as depicted inScheme 2since thelower anacardic acids are not available from natu-ral sources. The alkylation stage to give (22) wasfollowed by demethylation with boron tribromideproducing (23) and reduction of the ester with lithiumaluminium hydride, as inScheme 1, to afford thethree compounds represented by24.

3.5. Synthesis of 2-hydroxymethyl-4-alkylphenols

Homologous 2 - hydroxymethyl- 4- alkylphenolswere synthesised as shown inScheme 3from theappropriate 4-alkylphenol in the form of the phenoxy-magnesiobromide by reaction with paraformaldehyde(Casiraghi et al., 1978) and reduction of the aldehydeproduct with sodium borohydride.(b) (iii), (iv) as in(a), respectively.

The synthesis of certain homologous members ofthis group is shown inScheme 3(a) consisting of(19, R = t-Bu, t-C8H17, n-C9H19, t-C9H19). Apartfrom the n-nonyl member the 4-alkyl-substitutedphenols were all from petrochemical sources. Al-though as with the anacardic acids inScheme 1,the methylols could be formed by hydride reductionof a carboxylic or carbethoxy substituent, we hadfound that either formylation (Casiraghi et al., 1978;Tyman, 1981) (J.H.P. Tyman and S.J.A. Iddenten,unpublished work) and reduction with sodium boro-hydride or, direct methylolation, were two alternative


procedures. In the case of the parent phenol (R= t-nonyl) monoformylation proceeded regiospecificallyand borohydride reduction gave an overall 46.7%yield whereas hydroxymethylolation, which resultedin some disubstitution (2,6-dihydroxymethyl-4-3,5,5-trimethylhexylphenol, 42.4%), gave 30.0% of themonohydroxymethyl compound, although the direct-ness of the latter method is an advantage (this workwith A. Ninagawa, will be reported elsewhere). In (b)Scheme 3, the synthesis of the chloro-derivative (21),OCS, namely, 2-hydroxymethyl-6-chloro-4-(1,1,3,4-tetramethylutyl)phenol is shown. Monochlorination oft-octylphenol in carbon tetrachloride at ambient tem-perature gave a 96% yield of 2-chloro-4-t-octylphenolwhich 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 gave21 in 77.3% yield, in pure form. It appears thatprevious preparations of this extractant (Brown andSanderson, 1978b), were impure and were employedcontained both the starting material 4-t-octylphenoland 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 depictedin Scheme 4, either, by the Kolbe carboxylation ofcardanol to give isoanacardic acid (Durrani et al.,1980) (7) followed by lithium hydride reductionor, from isoanacardic aldehyde (8), available fromthe reaction of cardanoxymagnesium bromide withparaformaldehyde in the presence of HMPT, followedby reduction of (8) with sodium borohydride, orby hydroxymethylation in aqueous alkaline solutionwith formaldehyde. Hydroxymethylation of cardanolwith formaldehyde in aqueous alkaline solution af-forded isoanacardic alcohol (9) (37.3%), recoveredcardanol (42.4%), together with small proportions ofthe 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 themonomethylol was 71.2%.

3.7. Synthesis of homologous 2-hydroxymethyl-5-n-alkylphenols

In Scheme 5, the synthesis of certain homologous2-hydroxymethyl-5-alkylphenols (12, R1 = n-Bu, t-

Bu.,n-C8H17, n-C9H19 andn-C11H23 is shown. Wittigreaction (Maercker, 1965) of 3-hydroxybenzaldehydewith the required alkyltriphenylphosphonium bro-mide followed by catalytic hydrogenation of the re-spective alkene formed, gave the 3-alkylphenol (10).Formylation in the usual way of the phenoxymagne-sium bromide and reaction with paraformaldehydeafforded the respective aldehyde (11) and thence bysodium borohydride reduction, the required product.Alternative procedures (Caplin and Tyman, 1982;Tyman et al., 2002) to 3-alkylphenols by reaction of3-hydroxybenzaldehyde with 1-bromoalkanes in THFcontaining lithium, followed by catalytic hydrogenol-ysis, also afford excellent yields.

3.8. Synthesis of 2-hydroxymethyl-6-alkylphenols

The synthesis of two homologous 2-hydroxymethyl-6-alkylphenols is depicted inScheme 6(a and b).2-n-Nonylphenol (13), obtained by a Wittig reactionwith salicylaldehyde followed by catalytic hydrogena-tion, was formylated as the phenoxymagnesium bro-mide by reaction with paraformaldehyde to afford thealdehyde (14) which was reduced by sodium borohy-dride to give 2-hydroxymethyl-6-n-nonylphenol (15,R1 = n-C9H19). The t-octyl analogue (15, R1 = t-C8H17) was synthesised byt-octylation of phenol togive 16, followed by formylation and reduction of thealdehyde product (17) with sodium borohydride.

Alternative methods for formation of methylolsby catalytic hydrogenation with copper chromite(Adkins, 1954), rhenium catalysts (Broadbent andBartley, 1963) and by electrolytic reductionRifi andCovitz, 1974) are available, but were not examined inthis present exploratory work.

3.9. Solvent extraction properties of 1,2- and1,3-diols

The complexation and solvent extraction of borateleading to the recovery of boric acid by compoundsdescribed in this account will be described in detailelsewhere. Unsaturated anacardic alcohol (5) appearsto be a superior extractant to itsiso-analogue (9) over awide pH range. By contrast, OCS (21) and its dechloroanalogue (19, R = C8H17) and the 4-t-nonylphenolanalogue (19, R = C9H19) are only more effectiveat a higher pH but rapidly decline and are inferior


at normal (neutral) pH values. Urushiol (4) is lesseffective over the whole pH range. However, in thepresence of Aliquat 336 (tri-t-octylamine), the perfor-mance of unsaturated anacardic alcohol, isoanacardicalcohol, the 4-t-nonylphenol analogue and urushiolis enhanced, but again unsaturated anacardic alcoholand its iso analogue are the most effective of thesemi-synthetic series of lipidic diols. The usage ofdiols from natural replenishable sources would enablefossil fuels to be employed preferentially for energyrather than for chemical uses. It is also relevant thatcertain phenolic lipid products from natural sourceshave been found to be more biodegradable than theirpetrochemical analogues (Tyman and Bruce, 1992;Tyman and Bruce, 2003).

Acknowledgements

Borax Research are thanked for partial financialsupport and for laboratory facilities.

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