Preparation of Substituted Anisylic Phenyl Ethers J. M. PROKIPCAK AND T. H. BRECKLES Department of Chemistry, University of Guelph, Guelph, Ontario Received October 14, 1970 It is shown that anisylic phenyl carbonates thermally decompose to yield the corresponding anisylic phenyl ethers. The method involves heating the carbonates to their decomposition temperatures using hexamethylphosphoramide or toluene as a solvent. Thirteen anisylic phenyl ethers were prepared in good to excellent yields by this apparently general and simple procedure. 11 est dcmontrt que les carbonates doubles de phcnyle et d'anisyles se decomposent thermiquement pour fournir les phcnoxy anisoles correspondants. La mcthode implique le chauffage des carbonates jusqu'a leur tempkrature de dccomposition dans I'hexamCthylphosphoramide ou le tolukne comme solvants. Treize Cthers ont CtC prcparcs, avec des rendements variant de bons a excellents, par cette mtthode simple et apparemment gcncrale. Canadian Journal of Chemistry, 49, 914 (1971) In the process of preparing some substituted benzyl phenyl carbonates for study in our laboratory, unexpected difficulty was encountered in purifying anisyl phenyl carbonate (p-methoxybenzyl phenyl carbonate) by distillation. Instead of obtaining the desired carbonate, a white solid was recovered which was tentatively assigned the structure of anisyl phenyl ether. Attempts to prepare the ether by conventional methods i.e. by reacting anisyl bromide with sodium phenoxide failed. This is in accordance with the difficulty encountered by Russell and Williamson (1) who found that using the aforementioned method, p-methoxy-p'-hydroxydiphenylmethane (1) was the major product formed (Scheme 1). Product 1 might be anticipated as the phenoxide ion could readily undergo electrophilic substitution by a very stable anisyl carbonium ion which could form from the anisyl bromide (2). A further survey of the literature revealed that very few anisylic phenyl ethers had been reported and thus it became of interest whether the pyrolysis reaction encountered in our laboratory could be used as a general synthetic route to the title compounds. All the carbonates were prepared by welldocumented conventional methods. substituted phenols were treated with phosgene to give the substituted phenyl chloroformates which were then reacted with the anisylic alcohols yielding the desired carbonates. The overall reaction scheme for the preparation of anisyl p-chlorophenyl carbonate and its subsequent thermal breakdown is shown in Scheme 2. Table 1 of the Experimental section lists the carbonates prepared in this study. When the pyrolyses of the carbonates were first attempted without the use of solvent, the decomposition temperatures ranged from 100-170" and the crude ether yields were 30-60%. Starting phenols were identified as the major side product along with other unidentified materials (possibly multi-substituted phenols). Use of dimethylsulfoxide (DMSO) and hexamethylphosphoramide (HMP) as solvent media lowered reaction temperatures by 10-25". However HMP had an additional advantage in that most of the carbonates which were decomposed using it as a solvent yielded ethers which crystallized after the pyrolysis was complete. In the case of p-methoxybenzhydryl phenyl carbonate, use of toluene as a solvent gave the most satisfactory results. In all the cases examined, the ether yields were good to excellent (see Table 2) and
PROKIPCAK AND BRECKLES: ANISYLIC PHENYL ETHERS 0 C I ~ O + H CI-C-CI II / Route 1 Route the amount of work required to obtain pure anisylic phenyl ethers from the corresponding carbonates was minimal. The thermal decomposition of these aralkyl carbonates could well follow the SNi mechanism established for the decomposition of alkyl chlorocarbonates (3) and more recently to that proposed for the decomposition of aralkyl thiocarbonates (4) (Scheme 3). The question of the timing of the different bond scissions cannot be commented on at this time i.e. whether the heterolysis of the aralkyl-oxygen bond and the carbonyl-phenoxy bond occurs simultaneously (route 2) or in two successive steps (route I). Extensive work has been carried out on the 2 kinetics of the decomposition along with some stereochemistry which will help elucidate the mechanism involved. This will be reported in a later paper. Experimental All melting points were determined on the Fisher-Johns m.p. apparatus and are uncorrected. Analyses were performed by Organic Microanalyses, 5757 Decelles Avenue, Montreal, Quebec. The n.m.r. spectra were measured on a Varian A60A instrument using tetramethylsilane as a standard and the i.r. spectra on a Beckman IR 5A. Preparation of Anisylic Alcohols Anisyl alcohol and 3,4-dimethoxybenzyl alcohol were available commercially and used without further purification. p-methoxybenzhydrol was prepared using a normal Grignard reaction. Phenyl magnesium bromide was
TABLE 1. The preparation of anisylic phenyl carbonates* Analysis (%) Carbonate Calculated Found n Melting point Yield Decomposition * R R' 03 (%) temperature CC) C H N CI C H N Cl F E p-methoxyphenyl 61.042.0 85 139 66.66 5.59 - - 66.97 5.51 - - > C H ~ - O ~ C H, p-methylphenyl 56.5-57.5 75 138 70.57 5.92 - - 70.66 5.78 - - z Phenyl 26.0-27.0 76 130 69.76 5.46 - - 69.92 5.64 - - 8 p-chlorophenyl 69.5-70.5 75 105 61.55 4.48-12.11 61.60 4.49-12.31 $ p-cyanophenyl 89.0-90.0 70 89 67.84 4.63 4.94-68.05 4.54 4.84-2 p-nitrophenyl 104.5-106.0(1 35t 70 59.41 4.32 4.62-59.32 4.37 4.42 - $ p-methoxyphenyl 70.5-71.5 85 139 64.14 5.70 - - 64.39 5.65 - - % C H 3 - O p c ~ 2 - pmethylphenyl 62.043.0 80 138 67.54 6.00 - - 67.47 5.92 - - - - n Phenyl 57.0-58.0 85 126 66.66 5.59 66.74 5.46 CH30 p-chlorophenyl 77.5-78.5 70 101 59.54 4.68-10.98 59.81 4.55-11.07 p-cyanophenyl 104.0-105.5 75 85 65.17 4.83 4.47-65.44 4.92 4.27 - i: p-nitrophenyl 123.0-124.0 35t 83 57.66 4.54 4.20-57.45 4.36 4.44-4 CH~-O+-~H- Phenyl 86.0-87.5 70 89$ 75.43 5.43 'The general structure was R--0--R'.?Yield was low due to difficulty in purifying the chloroformates. $Toluene was used as the solvent for decomposition. Literature (7). m.p. 28-29". IlLiterature (71, m.p. 96-97'. - -
TABLE 2. The preparation of anisylic phenyl ethers* 'a F Analysis (%) 0 E Ether Calculated Found Melting point Yield R R ' ("C) (%) C H N C1 C H N C1 7i * - - - - z p-methoxyphenyl 123.0-124.5 88 73.75 6.60 73.86 6.57 U CH~-O+CHZ- p-methylphenyl 88.0-89.0 92 78.92 7.06 - - 78.98 7.09 - - Phenyl 91.0-92.0t 96 78.48 6.59 - - 78.34 6.53 - - p-chlorophenyl 103.5-104.5 97 67.61 5.27-14.25 67.60 5.42-14.47 W p-cyanophenyl 127.0-128.0 92 75.29 5.48 5.85-75.24 5.40 6.07 - F p-nitrophenyl 106.0-108.0 60 64.86 5.05 5.40-64.70 4.97 5.58 - rn!? p-methoxyphenyl 88.0-89.0 93 70.06 6.61 - - 70.25 6.59 - - C H 3 - O p H z - p-methylphenyl 71.5-72.5 93 74.40 7.02-74.10 6.85-5 Phenyl 76.5-77.5 94 73.75 6.60 - - 74.02 6.51 - - 2 p-chlorophenyl 89.0-90.0 94 64.64 5.42-12.72 64.67 5.60 - CH30 12.93 p-cyanophenyl 118.0-119.0 65 71.36 5.61 5.20-71.36 5.46 5.37-0 p-nitrophenyl 142.5-144.0 58 62.28 5.23 4.84-62.34 5.40 4.64 - Phenyl 81.5-82.5 84 82.73 6.24 - - 82.83 6.27 - - ch~-o+h- 3 b c r: 8 "General structure is R-%R'.?Literature (a), m.p. 92-92.5'. 5
918 CANADIAN JOURNAL OF CHEMISTRY. VOL. 49, 1971 reacted with p-anisylaldehyde to yield p-methoxybenzhydrol, m.p. 65-66" (lit. (5) m.p. 6667") in a 70% yield. Preparation of Chloroformates Commercial grade phenyl chloroformate was used without further purification. The substituted phenyl chloroformates were prepared by reacting the properly substituted phenol with phosgene according to the method of Zabik and Schuetz (6) who had previously prepared all the chloroformates used in this study. Yields for the chloroformates were in general 70% or greater. Preparation of 3,4- Dimethoxybenzyl p-methoxyphenyl Carbonate The general method used in the preparation of the carbonates will be given. To a stirring solution of 40.0 g (0.238 mol) of 3,4-dimethoxybenzyl alcohol in 200 ml of anhydrous pyridine cooled to 0, was added dropwise 49.0 g (0.262 mol) of p-methoxyphenyl chloroformate. The mixture was then stirred at room temperature for 12 h. Methylene chloride (200 ml) was added and the mixture was extracted twice with 200 ml of 5 % HCI. The organic layer was then washed with200 ml of 5 % NaOH toremove any phenolic materials, washed with water, and dried over sodium sulfate. The solvent was removed in vacuo to give a white solid which was recrystallized from chloroform- petroleum ether (b.p. 30-60") to give 66.3 g (88%) of pure carbonate, m.p. 70-71'. The carbonate had the following spectral data: n.m.r.(cdc13)6(p.p.m.) 6.80-7.32 (7H multiplet, aromatic), 5.20 (2H singlet, methylene), 3.83 (6H singlet, benzyl CH&-), 3.77 (3H singlet, phenyl CH30--); i.r. (CCI,) 1754 (C=O stretch), 1265-1200 (ester C-0 stretch), and 1033 cm-' (R- 0-R' stretch). Anal. Calcd. for Cl7HI8o6: C, 64.14; H, 5.70. Found: C, 64.39; H, 5.65. The remainder of the carbonates were prepared in a similar manner and the details are shown in Table 1. The only variation in the method was in the case of the benzhydryl system where better results were obtained by reducing the amount of pyridine used by four-fifths. The spectral data for the carbonates prepared were consistent with the assigned structures. Pyrolysis of 3,4-Dimethoxybenzyl p-methoxyphenyl Carbonate In a typical experiment, 5.0 g (0.016 mol) of 3,4-dimethoxybenzyl p-methoxyphenyl carbonate was placed in 3 ml of hexamethylphosphoramide (HMP) and the solution was heated. When CO, began to evolve at a steady rate (limewater trap was used), the temperature (140") was kept constant. After 1 h an i.r. spectrum of the reaction mixture showed no starting material remained and the heating was stopped. Upon cooling, a solid formed in the reaction flask. Water (about 4 ml) was added dropwise to cause further precipitation and the solid formed was recovered by filtration; washed with water, and dried. Recrystallization from chloroform - petroleum ether (b.p. 30-60") yielded 4.0 g (93%) of pure 3,4-dimethoxybenzyl p-methoxyphenyl ether (m.p. 86-87"). The ether had the following spectral data: n.m.r. (CDCI3) 6 (p.p.m.) 6.92 (7H unresolved aromatic multiplet centered at 6.92), 4.92 (2H singlet, methylene), 3.84 (9H singlet, CH30-), 3.76 (3H singlet, phenyl CH30-); i.r. (CCI,) 1230 cm-' (C-0-C stretch). Anal. Calcd. for C16H1804: C, 70.06; H, 6.61. Found: C, 70.25; H, 6.59. All the thermal decompositions were carried out in a similar manner with use of toluene as a solvent being the only variation. Details are shown in Table 2. The assigned structures for the ethers prepared were supported by spectral data. The authors wish to thank the National Research Council of Canada for financial support of this research and the Department of University Affairs for the award of an Ontario Graduate Fellowship to T. H. Breckles. We also wish to thank Dow Chemical of Canada Ltd. for a generous supply of HMP. 1. G. A. RUSSELL and R. C. WILLIAMSON, JR. J. Amer. Chem. Soc. 86,2357 (1964). 2. B. G. RAMSEY and J. COOK. Tetrahedron Lett. 7, 535 (1969). 3. K. B. WIBERG and T. M. SHRYNE. J. Amer. Chem. SOC. 77, 2774 (1955). 4. J. L. KICE, R. A. BARTSCH, M. A. DANKLEFF, and S. L. SCHWARTZ. J. Amer. Chem. Soc. 87, 1734 (1 965). \-- --r. 5. M. P. BALFE, M. A. DOUGHTY, J. KENYON, and R. POPLETT. J. Chem. Soc. 605 (1942). 6. M. J. ZABIK and R. D. SCHUETZ. J. Org. Chem. 32, 300 (1967). 7. F. WEYGAND and K. HUNGER. Chem. Ber. 95, 1 (1961). 8. HI B.'HENBEST, J. A. W. REID, and C. J. M, STIRLING. J. Chem. Soc. 5239 (1961).