摘要:
J. CHEM. soc. PERKIN TRANS. 1 1993 Anodic Cyanation of tert-Butylated Anisoles: Competitive Aromatic Additions and Substitutions Kunihisa Yoshida," Kazusada Takeda and Takayuki Fueno Department of Chemical Engineering, Faculty of Engineering Science, Osaka University, Toyonaka,Osaka 560, Japan The electrooxidation of several tert-butylated anisoles has been carried out in methanol containing sodium cyanide at a Pt anode in a divided cell. Two types of reactions occurred competitively, aromatic-ring addition and substitution. Increasing the level of tert-butyl substitution raises the relative extent of addition to the aromatic ring. An MO calculation has indicated that the order of orientational preference for substitution of the aromatic hydrogen of alkylanisole cation radicals is explained in terms of the LUMO electron densities calculated for the cation radicals.The effect of structure on the oxidation potential of alkylanisoles has also been studied. para Substitution lowers the oxidation potential while ortho substitution raises the potential. Many of the electrooxidations of alkylated aromatic com- pounds are considered to proceed by way of monocation radical intermediates and it is common to observe products resulting from substitution on both the aliphatic side-chain and the aromatic nucleus.' Previously, we have reported a study of the electrooxidation of the three isomeric methylanisoles in methanol containing sodium cyanide.2 With ortho-and meta- methylated anisoles, nuclear cyanation took place preferen- tially while with p-methylanisole, side-chain methoxylation predominated.The data obtained was also compared with those of other electron-transfer reactions such as anodic acetoxyl- ation and acetoxylation and chlorination by metal oxidizing agents. It has been shown that positional reactivities are rationalized in terms of the LUMO electron densities calculated for the cation radical^.^ As part of our programme of electrochemical functionaliz- ation of alkylated aromatic compounds, the present paper describes the electrooxidation of several tert-butylated anisoles in methanol containing sodium cyanide. Not only does the tert-butyl substituent lack a proton but, like a methyl group, it releases electrons and activates the ring.Results Oxidation Potentials.-Cyclic voltammograms were recorded for a series of tert-butyl-substituted anisoles using a solution of 0.4 mol dm-3 NaCN in methanol. The reference electrode was an SCE (saturated calomel electrode). The background current with this system began to increase at potentials more anodic than 1.60 V. The observed E,, values are collected in Table 1. Products.-The oxidations, carried out at a constant current of 0.1 A in a divided cell with a R anode, at room temperature, were terminated after passage of 2.0 F mol-' of added substrate. After work-up, the products were isolated by preparative GLC and identified by elemental analysis and 'H NMR, IR and mass spectroscopic analyses (Table 2).Initially we studied terz-butylbenzene (TBB). All three possible isomeric tert-butylbenzonitriles were produced in a total yield of 3% (based on unrecovered starting material), the NC OMe conversion being 15%. Most of the current would be consumed in oxidation of the cyanide ion, an inorganic electrode process MexYBu'not producing isolable cyanated products. I tert-Butylanisoles (TBAs) undergo predominantly two types Bu' of aromatic-cyanation reactions: (1) substitution of aromatic 3 4 Table 1 Products and yields of electrooxidation of tert-butylated anisoles in NaCN-MeOH Substrate EP (V us. SCE) Conversion (%) Product Yield (%) TBB C- 15 la 1.5 lb 0.5 lc 1 2-TBA 1.71 89 If 36 1gla 23 20 Id 3 4-TBA 1.57 91 li 37 lc 26 le 4 2,4-DTBA 1.47 94 2a lh j22 11 17 lf 6 lk 2b * 1 14 2c 9 3 2 2,6-DTBA -' 43 In 1jlo 41 12 10 1g 1P 9 10 2,4,6-TTBA -1.8 69 2f' 2dg 17 40 2e 7 2g4 1.5 3 lm 8 11 4 In 4 Constant-current electrooxidation at 0.1 A.Pt anode; divided cell; electricity 2.0 F mol-'; substrate concentration 0.4 mol dmP3. * 0.4 mol dm-3 NaCN-MeOH; at v 0.1 V s-'. In these cases the oxidation wave was not observed due to the large background current from the concurrent electrooxidation of the solvent4ectrolyte system. 24%cis, 76%trans. 50%cis, 50% trans. 12%cis, 88% trans. 35% cis, 65% trans. 47%cis, 53% trans. Based on unrecovered starting material. j <0.5%yield. hydrogen and (2) replacement of an aromatic methoxy group.2-TBA gave hydrogen-displacement products, 3-tert-butyl-4- methoxybenzonitrile If (36%) and 3-tert-butyl-2-methoxy-benzonitrile lg (23%), together with the methoxy-displace- ment product, 2-tert-butylbenzonitrile la (20%). 4-TBA afforded 5-tert-butyl-2-methoxybenzonitrileli (37%) and 4-tert-butylbenzonitrile lc (26%), along with a small amount of 1,4-dicyano adduct 2a. In both cases, tert-butyl displace- ment occurred, although this is a minor pathway. Cyanation of di-tert-butylanisoles (DTBAs) occurred at their methoxy and/or tert-butyl groups as well as by replacement of aromatic hydrogen, 1,4 addition of cyano and/ or methoxy group(s) competing with aromatic substitution. Besides these, 2,4-DTBA underwent the 1,2-mixed addition of one cyano and one methoxy group with the formation of a small amount of 2,4-di-tert-butyl- 1,6-dimethoxycyclohexa-2,4-diene-1-carbonitrile 3.2,6-DTBA gave an abnormal hydrogen- displacement product, 2,6-di-tert-butyl-4-methoxybenzonitrile lp (lo%), produced by elimination of a methanol molecule from the 1,4-mixed addition product, 1,4-dimethoxy-2,6-di-tert-butyl-cyclohexa-2,5-diene-1-carbonitrile 2f, during GLC analysis. With 2,4,6-tri-tert-butylanisole(2,4,6-TTBA), the reaction mode was reversed and addition predominated over substitu- tion. At the 3 position, there was no substitution of the aromatic- hydrogen but 1,Qaddition of two cyano groups across the benzene ring occurred with formation of the adduct 2g.J. CHEM. SOC. PERKIN TRANS. 1 1993 Compound 4 is a secondary product of 1,3,5-tri-tert-butyl- 3,6,6-trimethoxycyclohexa-1,4-diene upon hydrolytic work-up. Structure Determination.-The result of previous 'H NMR spectroscopic studies on geometrical isomerism in 2,5-di-hydrofurans, ' 2,5-dihydrothiophenes 2*1 and 2,3-dihydro- benzothiophenes l4 were applicable to structural assignments of isomeric pairs of the relevant cyclohexadienes 2. The chemical shift of a group in the 1 position of the cyclohexadiene ring is affected both by the other group at the 1 position and the magnetic influence exerted by the group at the 4 position that is cis to it. Thus, if a 1-methoxy group is cis to a 4-methoxy (or a 4-cyano) group it will resonate at a lower field and raise the 6 value compared with the values obtained if it is cis to a 4-tert-butyl (or a 4-protium) group.The structure assigned to 2g was based on its spectroscopic characteristics. The C2 1H3,N20 molecular formula was indi- cated by mass spectroscopy and verified by elemental analysis. The IR spectrum indicated the presence of a cyano group. The NMR spectrum showed three tert-butyl resonances at 1.25 (9 H, s), 1.30 (9 H, s) and 1.34 (9 H, s), a doublet at 3.36 (1 H, methine bonded to a cyano group), one methoxy resonance at 3.54 (3 H, s) and one olefinic proton at 5.80 (1 H, d). The structural assignment to compound 3 was also supported by its combustion analysis and mass, IR and NMR spectra.NMR spectroscopy (S in CDC13) showed two tert-butyl resonances at 1.10 (9 H, s) and 1.28 (9 H, s), two methoxy protons at 3.34 (3 H, s) and 3.60 (3 H, s), one doublet at 4.10 (1 H, methine bonded to a methoxy group) and two olefinic protons at 5.74 (1 H, dd) and 6.10 (1 H, d). Discussion The cyanation of several tert-butylated anisoles has been investigated. Two types of reactions are observed: aromatic ring substitution is favoured for anisoles having a tert-butyl sub- stituent on either the ortho or para (or both) position(s) and nuclear addition for compounds having the tert-butyl sub- stituent on all ortho and para positions. With increasing numbers of tert-butyl groups the relative extent of addition to the benzene ring is raised.Heretofore, anodic 1,4-addition of one cyano and one methoxy groups across the benzene ring has been reported for 1,4-dimethoxybenzene. 1,4,4-Trimeth-oxycyclohexa-2,5-diene-l-carbonitrile was isolated although it contained an impurity difficult to separate. The Effect of Structure on Oxidation Potentia1.-The oxidation wave of the parent anisole was not observed since it was marked by the large background current from the concurrent electrooxidation of the solvent4ectrolyte system. The potentials depend upon the number and position(s) of the substituent. As can be seen from Table 1, para substitution lowers the oxidation potential while ortho (markedly di-ortho) substitution, where steric effects can prevail, raises the potential. For comparison, Epsfor ortho-methyl- and para-methyl-anisole were measured (1.75 and 1.55 V us.SCE at v 0.1 V s-l, respectively) and compared with those of the corresponding tert- butylated anisoles. It was ascertained that there is little difference in the substituent effects between tert-butyl and methyl groups. A similar substituent effect appears in the conversion of substrates in the present electroreaction. The results are shown in Table 1. Orientation.-Both addition and substitution on the benzene ring are formally a 2-equiv. change. The cyclic voltammetric characteristics indicate that oxidation is initiated by electron transfer from the substrate molecule, followed by a fast chemical reaction. By analogy with anodic cyanation and related func- J.CHEM. soc. PERKIN TRANS. 1 1993 Table 2 Spectroscopic data of electrooxidation products Mass Product 'H NMR [&(J/Hz)lbb m/z(M') IR (~,,,,,/m-')~~ la" 1.52 (9 H, s), 7.14-7.72 (4 H, m) 159 2220 (CN) lbb 1.32 (9 H, s), 7.3C7.50 (2 H, m), 7.5C7.66 (2 H, m) 159 2220 (CN) lc 1.32 (9 H, s), 7.367.64 (4 H, m) 159 2220 (CN) Id 1.37 (9 H, s), 3.82 (3 H, s), 6.70-6.95 (2 H, m), 7.02-7.32 (2 H, m) le 1.28 (9 H, s), 3.78 (3 H, s), 6.81 (2 H, dm, J8.6), 7.27 (2 H, dm, J8.6) If 1.36 (9 H, s), 3.88 (3 H, s), 6.80-6.92 (1 H, m), 7.38-7.54 (2 H, m) 189 1025,1095 (C-O-C), 2210 (CN) 1g' 1.36(9 H, s),4.12(3 H,s), 6.9-7.1 (1 H,m), 7.3-7.6(2H, m) 189 1000,1095 (C-O-C), 2210 (CN), 2870 (OMe) Ihf 1.31 (9 H, s), 1.51 (9 H, s), 7.1-7.7 (3 H, m) 215 2200 (CN) lig 1.28 (9 H, s), 3.90 (3 H, s), 6.74-6.92 (1 H, m), 7.47.6 (2 H, m) 189 1020, 1105, 1140 (C-O-C), 2220 (CN), 2860 (OMe)Ij" 1.54 (18 H, s), 7.3-7.4 (3 H, m) 215 2200 (CN) Ik' 1.35 (9 H, s), 1.48 (9 H, s), 3.82 (3 H, s), 7.06 (1 H, s), 7.34 (1 H, s) 245 1060,1115 (CGC), 22 10 (CN), 2870 (OMe) 11' 1.28(9H,s), 1.36(9H,s),4.08(3H,s),7.38(1H,d,J2.3)7.50(1 H,d,J 245 1000, 1120 (C-O-C), 2210 (CN) 2.3) Im 1.32 (9 H, s), 1.56 (18 H, s), 7.34 (2 H, s) 27 1 2280 (CN) In' 1.40 (18 H, s), 3.70 (3 H, s), 7.50 (2 H, s) 245 1000, 1120 (C-O-C), 2220 (CN) lo 1.40 (9 H, s), 1.64 (9 H, s), 3.58 (3 H, s), 7.16 (1 H, d, J8.1), 7.34 (1 H, d, J 245 1020, 1045 (C-0-C), 2210 (CN) 8.1) 1P" 1.54 (18 H, s), 3.84 (3 H, s), 6.84 (2 H, s) 245 2210 (CN) 2a-cis 1.12 (9 H, s), 3.36 (3 H, s), 6.0-6.4 (4 H, m) cc 960,970, 1055, 1090 (C-O-C), 2210 (CN) 2a-trans 1.10 (9 H, s), 3.46 (3 H, s), 6.20 (4 H, s) cc 960,1075 (CUC), 2225 (CN) 2b-cisO 0.92 (9 H, s), 1.34 (9 H, s), 3.02 (3 H, s), 3.34 (3 H, s), 6.S6.1 (3 H, m) 277 1075 (C-0-C) 2b-trans 0.92 (9 H, s), 1.34 (9 H, s), 3.00 (3 H, s), 3.30 (3 H, s), 6.06 (1 H, d, J2.3), 277 1075 (C-O-C), 2820 (OMe) 6.12(1 H,d,J2.3),6.14(1 H,s) 2c-cisq 1.10 (9 H, s), 1.34 (9 H, s), 3.26 (3 H, s), 6.0-6.3 (3 H, m) 272 975, 1020, 1045, 1075, 1090 (CUC), 2220 (CN)2c-trans 1.10 (9 H, s), 1.34 (9 H, s), 3.40 (3 H, s), 6.0-6.3 (3 H, m) 272 955,975, 1075, 1085 (C-O-C), 2220 (CN) 2d-cis" 0.94 (9 H, s), 1.41 (18 H, s), 3.00 (3 H, s), 3.04 (3 H, s), 6.17 (2 H, s) cc 1075, 1095 (C-O-C), 2220 (CN) 2d-trans' 0.96 (9 H, s), 1.41 (18 H, s), 2.94 (3 H, s), 2.96 (3 H, s), 6.16 (2 H, s) 333 1065,1095 (C-O-C), 2220 (CN), 2820 (OMe) 2e-cis' 1.10 (9 H, s), 1.41 (18 H, s), 2.92 (3 H, s), 6.24 (2 H, s) cc 1065, 1095 (C-OX), 2225 (CN) h-trans" 1.12 (9 H, s), 1.41 (18 H, s), 2.93 (3 H, s), 6.24 (2 H, s) cc 965, 1085 (CUC), 2220 (CN) 2f-cis 1.38(18H,s),2.94(3H,s),3.34(3H,s),4.28(1H,t,J3.1),6.28(2H,d,J 277 ee 3.1) 2f-trans 1.38(18 H,s),2.84(3 H,s), 3.16(3 H,s),4.45(1 H, t,J3.1), 6.28(2H,d, J 277 1060, 1090 (C-O-C), 2210 (CN), 2825 (OMe) 3.1) 2g 1.25 (9 H, s), 1.30 (9 H, s), 1.34 (9H, s), 3.36 (1 H, d, J0.7), 3.54 (3 H, s), 328 1095, 11 35 (C-O-C), 2230 (CN) 5.80 (1 H, d, J 0.7) 3' 1.10(9H,s), 1.28(9 H,s), 3.34(3 H,s), 3.60(3 H,s),4.10(1 H, d,J5.1), 277 1100,1120 (C-O-C), 2210 (CN), 2825 (OMe) 5.74(1H,dd,J5.1,1.4),6.10(1H,d,J1.4) 0.94 (9 H, s), 1.25 (18 H, s), 3.14 (3 H, s), 6.51 (2 H, s) 292 1075 (C-O-C), 1640 (CX), 1660 (W),4 2850 (OMe) " Ref.4. Ref. 5.' Ref. 6. Ref. 7. Found: C, 76.1; H, 7.9; N, 7.7. C,,H,,NO,requires C, 76.2; H, 8.0; N, 7.4%. Found: C, 83.6; H, 9.9; N, 6.6. ClsH,,NrequiresC,83.7;H,9.8;N,6.5~.gFound:C,75.7;H,8.1;N,7.8.C,,H,sNOrequiresC,76.2;H,8.0;N,7.4~.hFound:C,83.7;H,9.9;N, 6.5.ClsH2,NrequiresC,83.7;H,9.8;N,6.5%.'Found:C,77.9;H,9.5;N,5.8.Cl,H,,NOrequiresC,78.3;H,9.5;N,5.7%.jFound:C,78.2;H,9.5; N, 5.7. C,,H,,NO requires C, 78.3; H, 9.5; N, 5.7%. Ref. 8. Ref. 9. Found: C, 78.1; H, 9.6; N, 5.8. C,,H,,NO requires C, 78.3; H, 9.5; N, 5.7%. " This material was isolated containing 2f as an impurity difficult to separate.Found: C, 73.6; H, 9.8; N, 5.2. C,,H,,NO, requires C, 73.6; H, 9.8; N, 5.1%. P Found: C, 73.6; H, 9.7; N, 5.1. C,,H,,NO, requires C, 73.6; H, 9.8; N, 5.1%. Found: C, 75.0; H, 9.0; N, 10.0. C,,H2,N0, requires C, 75.0; H, 8.9; N, 10.3%. Found: C, 74.8; H, 8.9; N, 10.1. C,,H,,N02 requires C, 75.0; H, 8.9; N, 10.3%. 'Found: C, 75.6; H, 10.2; N, 4.4. C,,H,,NO, requires C, 75.6; H, 10.6; N, 4.2%. Found: C, 75.6; H, 10.2; N, 4.4. C,,H,,NO, requires C, 75.6; H, 10.6; N, 4.2%. 'Found: C, 76.7; H, 9.6; N, 8.5.C,,H,,N,O requires C, 76.8; H, 9.8; N, 8.5%. " Found: C, 76.7; H, 9.8; N, 8.5. C,,H,,N,O requires C, 76.8; H, 9.8; N, 8.5%. This material was isolated containing lp as an impurity difficult to separate.Spectral analyses take this impurity into account. Found: C, 74.0; H, 9.8; N, 5.2.C,,H2,N0, requiresC,73.6;H,9.8;N, 5.1%.y Found:C, 76.5;H,9.7;N,8.2. C,,H,,N,Oreq~iresC,76.8;H,9.8;N,8.5%.~Found:C,73.6;H, 9.8; N, 5.1. C,,H,,NO, requires C, 73.6; H, 9.8; N, 5.1%. Found: C, 77.3; H, 10.8. C19H3202 requires C, 78.0; H, 11.0%. bb 100 MHz; CDCl, solution; standard Me,%. ''The parent peak was not observed. dd Mull for solid sample. ee The CN stretching vibration of lp as impurity masks that of this product. tionalization of other aromatic compounds,' the ECEC in determining the positional reactivity in the aromatic ring. mechanism involving a cation-radical intermediate would be Results of an MO calculation using the method of intermediate reasonable.neglect of differential overlap (INDO) in the unrestricted The generalized mechanism presented in Scheme 1 accounts Hartree-Fock (UHF) procedure (the INDO-UHF method) for anodic bond formation of tert-butylated anisoles, where R are shown in Fig. 1 for the methylanisole cation radicals. These represents the leaving group such as a hydrogen atom and tert- results clearly indicate that the order of orientational butyl and methoxy groups and Nu is the nucleophile. This preference for substitution of aromatic hydrogen of alkylanisole mechanism involves two competitive pathways, addition and cation radicals may be explained in terms of the LUMO substitution. The bond-forming step is, however, common in electron densities calculated for the cation radicals (ie., charge- both reactions, namely, addition of a nucleophilic anion to an transfer interaction) rather than net-positive-charge distribu- unsaturated carbon atom of the anodically generated cation tions (i.e., electrostatic interaction).radical. The replacement of methoxy and tert-butyl groups during Our previous studies indicate that the charge and electron aromatic cyanation has also been observed. If the substituent density in an aromatic cation radical will be an important factor already on the ring is a good cationic leaving group, @so CN R2 Scheme 1 addition, the first step of @so substitution by a nucleophile, can take place to a greater extent than is suggested by the LUMO electron densities. Experimental General.-Spectrometers and electrochemical equipment have been described previously.lo Materials.-Methanol and reagent-grade sodium cyanide were used without purification. TBB, 4-TBA and 2-methoxy- and 4-methoxy-benzonitrile were obtained commercially. The following materials were prepared according to literature procedures: 2-TBA,I6 2,4- DTBA,” 2,6-DTBA,I8 2,4,6-TTBA,I9 3-tert-butylbenzonitrile lb and 3-tert-butyl-4-methoxybenzonitrilelf.20 Cyclic Voltammetry (CV).-Voltammograms were recorded for each anisole as described previously.2 The reference elec- trode was an SCE. There was no cathodic peak corresponding to reduction of an initially formed cation radical in any of the voltammograms. The Epvalues are in Table 1. Constant-current E1ectroreaction.-The electroreaction was carried out in a two-compartment H-type cell with a glass frit separating the compartments fitted with Pt sheet electrode (2 x 4 cm).The anolyte was made up of the organic substrate (0.02 mol), NaCN (2.0 g, 0.04 mol) and MeOH (50 cm3). The catholyte was the same medium in the absence of the substrate. The anode and cathode compartments were kept under nitrogen and the solution was stirred magnetically. The reaction was performed at 0.1 A of constant current by using a direct- current power supply at room temperature until 2.0 F mol-’ of added substrate had passed through the solution. After completion of the oxidation, the anolyte was treated with brine and extracted with diethyl ether. The extract was concentrated under reduced pressure and analysed by GLC.The columns employed for the analyses were Silicone GE SE-30 or Silicone OV-17. Each product was separated in pure form J. CHEM. soc. PERKIN TRANS. 1 1993 OMe OMe 0.1l(0.05) O.OZ(0.05) 0.00(0.02) 0.01(0.03) 0.1q0.10) 0.14(0.12) Me Fig. 1 LUMO electron densities and net-positive-charge densities of the cation radicals calculated by the INDO method in the unrestricted Hartree-Fock procedure. The value in parentheses represents the net- positive-charge density. by preparative GLC. Known compounds were identified by spectral comparison with authentic samples. The structures of unknown compounds were determined by their spectroscopic characteristics and elemental analyses (Table 2).CAUTION: a cyanide salt in MeOH must be handled in a fume hood since it contains HCN as a result of the equilibrium between CN- and the solvent MeOH. References 1 See e.g. K. Yoshida, Electrooxidation in Organic Chemistry, Wiley-Interscience, New York, 1984; Krieger, Malabar, Florida, 1993. 2 K. Yoshida, M. Shigi and T. Fueno, J. Org. Chem., 1975,40,63. 3 Ref. 1, p. 113. 4 T. Hayashi, K. Watanabe and K. Hata, Nipponn Kagaku Zasshi, 1962,83, 348 (Chem. Abstr., l963,59,3826g). 5 M. S. Newman and E. K. Easterbrook, J. Am. Chem. SOC.,195577, 3763. 6 T. L. Brown, J. Am Chem. Soc., 1959,81,3232. 7 F. R. Hewgill and G. B. Howie, Aust. J. Chem., 1978,31,907. 8 P. L. Russell and R. M. Topping, J. Chem. SOC.C, 1969, 1 134. 9 L. A. Cohen and W. M. Jones, J. Am. Chem. SOC.,1962,84,1625. 10 K. Yoshida and T. Fueno, Bull Chem. SOC.Jpn., 1987,60,229. 11 K. Yoshida and T. Fueno, J. Org. Chem., 1971,36, 1523. 12 K. Yoshida, K. Takeda and K. Minagawa, J. Chem. SOC.,Perkin Trans. I, 1991, 11 19. 13 K. Yoshida, K. Takeda and T. Fueno, J. Chem. SOC.,Perkin Trans I, 1991,2817. 14 K. Yoshidaand K. Miyoshi, J. Chem.SOC.,Perkin Trans. I, 1992,333. 15 N. L. Weinberg, D. H. Marr and C. N. Wu, J. Am. Chem. SOC.,1975, 97, 1499. 16 G. Stork and W. N. White, J. Am. Chem. SOC.,1956,78,4604. 17 M. S. Carpenter, W. M. EasterandT. F. Wood, J. Org. Chem., 1951, 16, 586. 18 N. Kornblum and R. Seltzer, J. Am. Chem. SOC.,1961,83,3668. 19 A. McKillop, J.-C. Fiaud and R.P. Hug, Tetrahedron, 1974,30,1379. 20 F. R. Hewgill and G. B. Howie, Aust. J. Chem., 1978,31,907. 21 K. Yoshida, J. Am. Chem. SOC.,1979,101,2116. Paper 3103904H Received 6th July 1993 Accepted 9th September 1993
ISSN:1472-7781
DOI:10.1039/P19930003095
出版商:RSC
年代:1993
数据来源: RSC