この論文は国立情報学研究所の学術雑誌公開支援事業により電子化されました。A new synthetic method for the preparation of guaiacylglycerol-β-coniferyl and β-coniferyl aldehyde ethers, representing the most important lignin substructure are described as one in a series of synthetic studies of lignin model compounds

HIGUCHI, Takayoshi

NAKATSUBO, Fumiaki

Kyoto University Research Information Repository

Title Synthesis of Guaiacylglycerol-β-Coniferyl and β-ConiferylAldehyde EthersAuthor(s)NAKATSUBO, Fumiaki; HIGUCHI, TakayoshiCitationWood research : bulletin of the Wood Research Institute KyotoUniversity (1980), 66: 23-29Issue Date1980-02-12URL http://hdl.handle.net/2433/53356RightType Departmental Bulletin PaperTextversionpublisherKyoto UniversitySynthesis of Guaiacylglycerol-J3-Coniferyland J3-Coniferyl Aldehyde EthersFumiaki NAKATSUBO* and Takayoshi HIGUCHI'"Abstract--A new synthetic method for the preparation of guaiacylglycerol-,B-coniferyland ,B-coniferyl aldehyde ethers, representing the most important lignin substructure aredescribed as one in a series of synthetic studies oflignin model compounds.IntroductionThe arylglycerol-tJ-aryl ether substructure is the most important in lignins. It hasbeen reported that 30 to 50% or more of the phenylpropane units are found in thesestructures1 ,2). For this reason, guaiacylglycerol-,B-guaiacyl ether has been used as alignin model compound for studying various lignin reactions, such as in pulping, inchemical utilization and in biodegradation. However, this compound is not trulyrepresentative of the lignin structure, because the fJ-aryl ether residues in lignins containC3-side chains. To study the effect of chemical changes on functional groups in theside chains of tJ-aryl ether substructures, it is desirable to use structural models contain-ing ally alcoholic or ally aldehyde type side chains, which do occur in lignins. Guaia-cylglycerol-tJ-coniferyl (5) and tJ-coniferyl aldehyde (4) ethers, therefore, are suitablemodel compounds. Guaiacylglycerol-tJ-coniferyl and tJ-coniferyl aldehyde ethers havebeen isolated in low yields as lignin hydrolysis products3,4), and as products formed bythe oxidative coupling of coniferyl alcohoI5,6). However, the separation and purifi-cation of the two ethers are difficult because many other products are formed both inthe hydrolysis and in the dehydrogenation, and compounds are obtained as a mixtureof er.ythro and threo isomers which cannot be purified by crystallization.The present paper, one in a series of synthetic studies of lignin model compounds,r~ports the new synthetic method for preparing guaiacylglycerol-,B-coniferyl (5) andtJ-coniferyl aldehyde (4) ethers.Results and DiscussionThe synthetic method for the target ethers is analogous to that used to prepareguaiacylglycerol-tJ-guaiacyl ether7) and a trilignol composed of phenylcoumaran andfJ-O-4 structures8). For the present synthesis (Fig. I), coniferyl aldehyde and vanillin* Division of Lignin Chemistry- 23-OH4WOOD RESEARCH No. 66 (1980)a77%~HPO~CHOO~ dOCH3 --9-0-%------'~~OCH3O~C30:)/1 "'.;;::: 00:--" b-c--~~OCH3 67.5%OCH33Fig. 1. Synthetic route of guaiacylglycerol-,R-coniferyl (5) and p-coniferyl aldehyde (4) ethers.aLithium diisopropyl amide/THF/-78°C bLiAIH4/THF/50°C cIN-HCI/THF/O°CdNaBH4/MeOH/O°Care used as the starting materials instead of guaiacol and the phenylcoumaran.The condensation of compound (1) with (2) by the use of lithium disiopropylamide (LDA) gives the expected compound (3), with the small amounts of the startingmaterials and polar impurities. Purification by silica gel TLC (PF-254 Merck),developed with ethyl acetate/n-hexane (1 :1), gives the pure compound (3). The useof silica gel chromatography (Wako gel C-lOO) for large-scale preparation, resulted ina partial deacetalization. Thus, the purification is carried out after the subsequentLAH reduction or at the stage of compound (4). The structure of compound (3) issupported by IR, which shows the absorption of the ester group at 1760 cm-I, and byNl\1R spectra. The compound (3) is a mixture consisting of the e~ythro and threoisomers; the ratio was found to be about 3.5:1.0 by the NMR spectrum, which showsclearly distinguishable peaks of the ester protons at 83.55 (s, threo) and 83.68 (s, er.J!thro)and of the tJ-methin proton at 84.48 (d, J =6.0, threo) and 84.66 (d, J =5.3, erythro).The er)Jthro isomer might be expected to predominate from the reaction mechanisminvolving a six-membered transition state intermediate.- 24-NAKATSUBO: Synthesis of Guaiacylglycerol-,B-Coniferyl and ,B-Conferyl Aldehyde Ethers10d..-OAelthreol/' -OAe (threo)Ol-OAe{erythrol,...-/t -OAe( erythrol2030g·O4.0~ (PPM)erythro-¥<0' threo-!f> ~-"--.5.0L1006062 60S"6.06<J,CH !erythrol~ (J=5.3)I~OIOIFig. 2. NMR spectrum of acetylated guaiacylglycerol-,B-coniferyl aldehyde ether (4)..-0 -OAelerythrol~..A:ond <l.-OAelerythro)cI--OAc!threola-OAe (threol,/102.0305060 . 40S"IPPMIFig. 3. NMR spectrum of acetylated guaiacylglycerol-,B-coniferyl ether (5)70- 25-WOOD RESEARCH No. 66 (1980)Compound (3) was subjected sequentially to lithium aluminium hydride reductionin THF at 50°C (75%), and to hydrolysis with IN-HC1/THF (1 :2) at O°C (90%) toafford the expected compound (4). The yield of compound (4) from the startingmaterial (1) is about 52%. Compound (4) was converted to the final compound (5) bysodium borohydride reduction in methanol at O°C (90%). The structures ofcompound(4) and (5) are supported by UV, IR, MS and NMR, as described in the Experimentalsection. The NMR spectra of the acetyl derivatives are shown in Figs. 2 and 3. It isnoteworthy that the peaks of the a-methin, y-methylene and a, y-alcoholic acetyl areclearly distinguishable between the erythro and threo isomers in the Nl\1R spectra. Theassignment of these protons based on the presumed reaction mechanism, which givespredominantly the erythro siomer, and also by comparision with the NMR spectra ofthe compound consisting of er.vthro/threo (about 1.0:1.1 ratio) obtained by the oxidativecoupling of coniferyl alcohol. a-Methin protons in erythro isomers, having a smallercoupling constant, appear at higher magnetic fields than in threo isomers. y-Methyleneand also y-alcoholic acetyl protons of er,.vthro isomers appear at lower magnetic fieldsthan these in the threo isomers.Experim.entalA HITACHI model 200-20 double beam spectrometer and a JASCO model IR-Swere used for UV and IR spectra, respectively. NMR spectra were taken with a HI-T ACHI R-22 high resolution NMR spectrometer (90 Mz), with TMS as internalstandard. Chemical shifts and coupling constants are given in S-values and Hz,respectively. Mass spectra were taken with a SHIMADZU -LKB 9000 gas chromato-graph-mass spectrometer; the relative aboundance of each peak is designated inparentheses. Kieselgel 60 PF-254 Gipshaltig (Merck) was used for silica gel TLCplates.Compounds (1) and (2)These compounds were prepared by the method reported previouslyS,9), andstored in a refrigerator to avoid partial decomposition of the acetals at room tempe-rature.Compound (3)To a stirred solution oflithium diisopropyl amide (5.6 mM) in 20 ml of anhydrousTHF, 1.37 g (4.66 mM) of coumpound (1) in 15 ml ofTHF was added dropwise overa period of about 40 min at -78°C under nitrogen. The reaction mixture graduallyturned to an orange-red color. The mixture was stirred for an additional 30 min,and 1.1 g (4.66 mM) of compound (2) in 15 ml of THF was added dropwise over aperiod of 30 min at the same temperature. The orange-red color of the solution- 26--NAKATSUBO: Synthesis of Guaiacylglycerol-,B-Coniferyl and ,B-Coniferyl Aldehyde Ethersgradually disappeared during the addition of compound (2) and finally turned to aslightly yellow. After stirring for an additional 30 min, the reaction mixture wasneutralized by the addition ofpowdered dry-ice. The solution was partitioned betweenethyl acetate and brine. The ethyl acetate layer was washed with brine, dried overNa2S04 and evaporated in vacuo to give a yellow-colored oil (2.5 g) which was used forthe subsequent LAH reduction without purification. An aliquot of the product ob-tained above was purified by silica gel TLC developed with ethyl acetate/n-hexane(I : I) for the NMR and IR measurements.IRI.i~~~c12 cm-1 : I 760. NMR(CDCL3) 8: 1.4-2.0(6H,m,-CH2-of THP), 3.4-3.7(2H,m, -CH2-O- ofTHP), 3.55(s, threo) and 3.63(s, erythro) (3H, two singlets, CH3-of methyl ester), 3.79 and 3.80(6H, two singlets, CH3- of methoxyl), 3.7-4.1 (4H,m,-CH2- of acetal), 4.48(d,J =6.0, threo) and 4.66(d,] =5.3, e~ythro) (lH, two doublet,P-CH-), 5.0-5.2(IH,m, a-CH-), 5.25-5.45(lH,m, -O-CH-O- of THP), 5.32(lH,d,J=5.7, -O-CH-O- of acetal), 5.59(IH, dd,] = 15.5, 5.7, P' = CH-) , 6.59(IH,d,] =15.5, a'-CH=), 6.6-7.1 (6H,m, aromatic).Compound (4)To a stirred solution ofLAH (497.8 mg, 13.1 mM) suspended in 20 mlofanhydrousTHF, 2.3 g of the crude yellow oil obtained above in 20 ml ofTHF was added dropwiseover a period of50 min at 50°C under nitrogen. After stirring for an additional 30 min,the reaction mixture was cooled to O°C and about 1 ml of water in 5 ml of THF wasadded dropwise to the solution to decompose the excess hydride. After the addition ofdry-ice to the solution, the reaction mixture was partitioned between ethyl acetate andwater. The aqueous layer was extracted twice with ethyl acetate. The combinedethyl acetate solution was washed with brine, dried over Na2S04 and evaporated invacuo to give a slightly yellow glass (2.3 g). An aliquot of the product was purified bysilica gel TLC developed twice with ethyl acetate/n-hexane (3 :2) for NMR analysis.NMR(CDCI3) 8: 1.9-2.0(6H,m, -CH2- of THP), 3.4-3.7(2H,m, -CH2-O- ofTHP), 3.78(6H,s, CH3- of methoxyl), 3.80-4.10(4H,m, -CH2-O- of acetal), 4.8-5.0(lH,m, a-CH) , 5.2-5.4(IH,m, -O-CH-O- of THP), 5.32(lH,d,] =6, -O-CH-O-of acetal), 5.96(lH,dd,]=16, 6, P'=CH-), 6.60(lH,d,]=16, a'-CH=), 6.15-7.10~6H,m, aromatic.)The product obtained above was purified on a silica gel column (Wakogel C-I0040 g, 2.6 X 10 cm) eluted with ethyl acetate/n-hexane (1: 1) to give the expected diolproduct (1.36 g, 58% overall yield from compound (1)) containing some partly hydroly-zed aldehyde; this mixture was used for the subsequent reaction as follows.To a stirred solution of the diol derivative (1.36 g, 2.71 mM) obtained above in15 ml of THF, 7.5 ml of IN-HCI was added dropwise at O°C under nitrogen. Afterstirring for 2 hours, the solution was partitioned between ethyl acetate and brine. The- 27-WOOD RESEARCH No. 66 (1980)ethyl acetate solution was washed with brine until the washings became neutral, andthen dried over Na2S04. Evaporation of the solvent in vacuo afforded a yellow glasswhich was purified by TLC developed twice with 3% methanol/methylene chloride togive the expected compound (4), pure by TLC, as a slightly yellow glass (913 mg, 90%).UV~:~Hnm(log s): 230(4.14), 336.5(4.27). IRLi~~~cm-l: 3500, 1665,1625,1595, 1520, 1510, 1465, 1450, 1425, 1275, 1220, 1130, 1020, 965. MNR(d6-acetone) 0: 3.40-3.80(2H,m, -CH-), 3.82(3H,s, CH30- of A-ring), 3.88(erythro) and3.92 (threo) (3H, two singlets, CH30- of B-ring), 4.51 (lH, broad q, J =4.5, P-CH),4.91(1H, broad d,J=5.5, a-CH-), 6.60(dd,J=16, 7.5, e~ythro), and 6.62(dd,J=16,7.5, threo) (lH, P'=CH-), 6.63-7.35(6H,m, aromatic), 7. 50 (er.J!thro) and 7. 52 (threo)(lH, two doublets, J=16, a'-CH=), 9.57(d,J=7.5, erythro) and 9.58(d,J=7.5, threo)(lH, y'-CHO). MS mje(%): 374(M+, 0.9), 356(4.2), 338(4.2), 326(33.2), 297(7.3),265(7.3),237(3.9),204(48.8), 178(100), 161(29.3), 151(38), 147(38), 137(61), 135(46.3),124(23.4),119(24.4),107(41),91(35.6), 89(32.7),77(52.7),65(34.1),51(40.5).Compound (5)To a stirred solution of compound (4) (194.2 mg, 0.52 mM) in 4 ml of methanol,9.5 mg (0.26 mM) of NaBH4 was added at O°C under nitrogen. After 30 min, theproduct was partitioned between ethyl acetate and brine. The ethyl acetate solutionwas dried over Na2S04 and evaporated in vacuo to give a colorless glass which was puri-fied by TLC developed with 5% methanol/methylene chloride to afford the purecompound (5) (176 mg, 90%) as a colorless glass.UVA~:~Hnm(1og s): 265.6(4.22). IRLi~~~cm-l: 3500,1605,1520,1270,1155,1130, 1085, 1028, 965,855. NMR(d6-acetone) 0: 3.82(3H,s, CH30- of A-ring),3.85(CH30- of erythro B-ring) and 3.89(CH30- of threo B-ring) (3H, two singlets),4.23(2H, broad d, J =5.0, y'-CH2, in one drop of D 20), 4.43(1H,q,J =5, P-CH' inone drop of D 20), 4.94(1 H, broad d,J =5, a-CH, in one drop of D 20), 6.23 (erythro )and 6.24(threo) (lH, two dt,J=16, 5.0, P'=CH-), 6.53(1H, broad d,J=16, a'-CH=),6.65-7.l5(6H,m, aromatic). MS m/e(%): 376(M+, 3.7), 358(3.7), 340(1.8), 328(12.9), 326(5.2), 206(48), 180(60), 162(23), 151(37), 137(100), 131(25), 124(48),119(38),91(49),77(33),65(33).Acetates of compounds (4) and (5)About 50 mg of compound (4) or (5) dissolved in 2 ml of THF was treated with2 m1 of acetic anhydride/pyridine (1 :1) overnight at room temperature. The reactionmixture was evaporated in vacuo and acetic anhydride/pyridine was removed azeotro-pically by evaporation with benzene. The products were purified by TLC(ethylacetate/n-hexane = 1:1) for the NMR measurements.NMR spectrum of acetyl compound (4) (Fig. 2) (DCCI3) 0: 1.98(threo) and 2.02(erythro) (3H, two singlets, y' -OAc) , 2.04(threo) and 2.09 (erythro) (3H, two singlets,- 28-NAKATSUBO: Synthesis of Guaiacylglycerol-p-Coniferyl and p. Coniferyl Aldehyde Ethersa'-OAc) , 2.26(3H, phenolic-OAc), 3.83(CH30- of A-ring and erythro B-ring) and3.87(CH30- of threo B-ring) (6H, two singlets), about 3.95-4.25(threo) and 4.26-4.70(erythro) (2H,m, y-CH2), 4.80(IH, broad q,] =5, P-CH) , 6.06(d,] =5.3, erythro) and6.11(d,]=6.0, threo) (lH, a-CH), 6.58(lH,dd,]=16, 7.8, P'=CH-), 6.78-7.20(6H,m,aromatic), 7.37(lH,d,]=16, a'-CH=), 9.62(lH,d,]=7.8, y'-CHO).NMR spectrum of acetyl compound (5) (Fig. 3) (CDCI3) 8: 1.96 (threo) and 2.00(erythro) (3H, two singlets, y-OAc), 2.02(threo a-OAc), and 2.08(erythro a-OAc andy'-OAc) (6H, two singlets, methoxyl), about 3.9-4.2(threo) and 4.2-4.6(erythro) (2H,m,y-CH2), 4.5-4.8(lH,m., P-CH), 4.68(2H, broad d,] =6, y'-CH2), 6.04(d,] =5.5, erythro)and 6.09(d,]=6.5, threo) (lH, two doublets, a-CH) , 6.12(IH,dt,]=16, 6,p'=CH-),6.56(lH, braod d,] = 16, a'-CH=), 7.65-7.10(6H,m, aromatic).AcknowledgementThe authors are grateful to Dr. T. K. Kirk, U.S. Forest Products Laboratory,Madison, Wisconsin, for critical reading of the manuscript.References1) K. V. SARKANEN and C. H. LUDWIG: "Lignins", john Wiley Sons, Inc., New Lork, p-165 (1970).2) T. HIGUCHI, T. TANAHASHI and F. NAKATSUBO, Wood Research, 54, 9 (1973).3) H. NIMZ, Chern. Ber., 98, 533 (1965).4) H. NIMZ, Chern. Ber., 100, 2633 (1967).5) K. FREUDENBERG and H. SCHLUTER, Chern. Ber., 88, 617 (1955).6) K. FREUDENBERG and B. LEHMANN, Chern. Ber., 93, 1354 (1960).7) F. NAKATSUBO, K. SATO and T. HIGUCHI, Holzforschung, 29, 165 (1975).8) F. NAKATSUBO, and T. HIGUCHI, Mokuzai Gakkaishi, 26, 31 (1980).9) Y. NAKAMURA, F. NAKATSUBO and T. HIGUCHI, Wood Research, 56, 1 (1974).- 29-

Synthesis of Guaiacylglycerol-β-Coniferyl and β-Coniferyl Aldehyde Ethers

http://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/53356/1/KJ00000017754.pdf

Synthesis of Guaiacylglycerol-β-Coniferyl and β-Coniferyl Aldehyde Ethers

Abstract

Similar works

Full text

Available Versions

Kyoto University Research Information Repository