In a 500 mL flask were placed 5.0 g (36.7 mmol) of p-anisaldehyde and 184 mL of methylene chloride (0.2M). This mixture was vigorously stirred with a magnetic stir bar. To the homogeneous solution was added 9.37 mL of 30% aqueous hydrogen peroxide (92.0 mmol., 2.5 equivalents) and 5.54 mL of formic acid (147 mmol., 4.0 equivalents). The flask was then fitted with a reflux condenser and heated to reflux for 20.5 hours with stirring.
After cooling, 119 mL of 1.5N sodium hydroxide (179 mmol., 4.86 equivalents) was added to the flask. The mixture was stirred for 15 minutes. The organic layer was separated and concentrated to a residue using a rotary evaporator. The residue was combined with the aqueous solution and 79.3 mL of methanol was added. The solution was stirred for 30 minutes. The methanol was removed using a rotary evaporator.
The neutral materials were removed from the aqueous residue by extracting with two 100 mL portions of methylene chloride. The solution was adjusted to a pH of 1 to 2 with concentrated hydrochloric acid. The 4-methoxyphenol was extracted with three 100 mL portions of methylene chloride.
The organic solution containing the neutrals as well as the one containing the product were separately dried over anhydrous magnesium sulfate and filtered into tared round-bottom flasks. The methylene chloride was removed using a rotary evaporator. A total of 0.052 g of neutrals was recovered. A total of 4.13 g of the crude 4-methoxyphenol was obtained (33.3 mmol., 90.7% yield).
The 4-methoxyphenol was purified utilizing bulb-to-bulb distillation. A mass of 3.88 g of 4-methoxyphenol as a white crystalline solid was obtained (31.3 mmol., 85.1 % yield). The purity was determined by GC (99.7%) as well as HPLC (99.3%).
p-Anisaldehyde (50 mmol) is dissolved in CH2Cl2 (100mL) and (o-NO2PhSe)2 (2 mmol) and 30% H2O2 (13mL, 128 mmol) are added. The mixture is stirred magnetically at room temperature (water bath) for 30 minutes. Insoluble catalyst is removed by filtration and washed with CH2Cl2 (20mL) and water (20mL). It can be reused after drying. To the filtrate and washings, water (100mL) is added, and the layers are separated after shaking. The organic layer is washed subsequently with 10% NaHSO3 (100mL), 10% Na2CO3 (100mL), water (100mL) and dried over Na2SO4. 4-methoxyphenol is obtained by alkaline hydrolysis of the residue. Yield: 93%.
4-Methoxyphenol was produced according to the process of this invention by charging 660 grams of hydroquinone (6 moles), 4800 grams of benzene, and 300 grams of water into a three necked flask fitted with a reflux condenser, stirrer, and two addition funnels. Then 480 grams of 50 percent aqueous sodium hydroxide (6 moles), and 756 grams dimethyl sulfate (6 moles; an equimolar quantity) were gradually added simultaneously at reflux (70°-75°C) during a period of about one hour keeping the alkali slightly ahead of the dimethyl sulfate.
The addition was made under a nitrogen atmosphere to minimize air oxidation of the hydroquinone but this is not essential to the success of the reaction. The mixture was refluxed for another one-half hour and then acidified to litmus with about 12 grams of acetic acid. The top oil layer was separated from the aqueous phase, washed with about 600 grams of a five percent sodium sulfate solution and distilled. After recovering the benzene, there was obtained a 122 gram head fraction distilling from 109-140°C/20mmHg, followed by 525g 4-Methoxyphenol at 141°C/20mmHg. From the head fraction, a mixt. of 1,4-dimethoxybenzene and 4-methoxyphenol, was obtained 53 g. 4-methoxyphenol by extn. with aq. NaOH followed by acidification. A total of 578.5g (78%) 4-methoxyphenol was recovered. From the non-alkali-sol. portion of the head fraction was obtained 64g (7.7%) 1,4- dimethoxybenzene. The combined aq layers were extd. with methyl isobutyl ketone. Evapn. of the solvent gave 52 g. of 96% pure hydroquinone.
The method of Ullmann7a for the semi-methylation of quinol (hydroquinone) was found to give poor yields and the following process was adopted after numerous trials. A solution of quinol (110 g) in sodium hydroxide (100g) and water (700 ml), contained in a flask filled with hydrogen, was cooled to 12°C and vigorously shaken after the addition of dimethyl sulphate (120 ml) in one portion. After about 5 minutes the mixture was cooled and the dimethyl ether collected (33g, mp 56°C). The filtrate and washings were acidified with hydrochloric acid and cooled to about 8 degrees for about 1 hour, thereafter the monomethyl ether was collected, washed with ice water, and dried (45 g., mp 52-54°C). The aqueous solution was extracted with ether and the residue after evaporation of the solvent yielded to benzene a further 30g of less pure quinol monomethyl ether, mp 41-46°C. For our purposes, it was necessary to ensure the absence of quinol from the product. The material was dissolved in benzene and any quinol which crystallized was separated; the solution was then distilled and a product, mp 53-54°C, collected at 243-246°C. This was redissolved in benzene, and the solution repeatedly shaken with small quantities of cold water. The ether was then again distilled, bp 243-244°C, mp 56°C. No coloration was developed in alkaline solution in contact with air. The substance crystallised from light petroleum has mp 56°C, but when heated to about 200°C and quickly cooled, the mp is 53°C, changing in a week or two to 55°C. Crystals, mp 56°C, also change on keeping and the mp becomes 55°C. Although these changes are small, the phenomenon is a real one.
Related are also a few older german refs for basically the same reaction sans the hydrogen atmosphere.7a,b,c
5.0 g of hydroquinone, 40 mL of methanol and 1.0 g of cupric chloride are fed into a teflon-lined autoclave having an internal capacity of 100 mL. The autoclave is purged with nitrogen and is kept for 2.5 hours at 105°C. On termination of the reaction, an analysis of the mixture indicates the formation of 4.1 g of hydroquinone monomethyl ether (conversion 85%, selectivity 87%).
Sample | Benzoquinone |
4-MeO-Phenol |
Hydroquinone |
After 3 h |
0.12 g | 14.6 g | 3.6 g |
After 6 h |
0.00 g | 15.8 g | 2.8 g |
Hydroquinone (18 g) and benzoquinone (2 g) in methanol (100 ml) with p-toluenesulfonic acid (5 g) were heated under reflux for 6 hours. Samples taken at 3 and 6 hours were analyzed by GLC and found to have the compositions indicated in the table.
A major part of the article is a kinetic study of the reaction of hydroquinone with primary aliphatic alcohols in the presence of quinhydrone and H2SO4. The method is based on
| R | Yield | mp |
| CH3 | 80.0% | 54-55°C |
| C3H7 | 64.1% | 55-56°C |
| C4H9 | 48.8% | 64-65°C |
| i-C4H9 | 17.2% | 64-66°C |
| C5H11 | 30.2% | 46-47°C |
| C6H13 | 28.2% | 47-48°C |
| C7H16 | 7.7% | 59-60°C |
4-Alkoxyphenols, ROC6H4OH.
a. (R = CH3, C3H7, C4H9, i-C4H9). A thermostatted glass reactor equipped with a magnetic stirrer and a reflux condenser was loaded with hydroquinone (8 g), quinhydrone (3 g), an alcohol (ROH, 100 ml) and sulfuric acid (8 ml). The mixture was stirred at 70°C for 20 min; the unreacted alcohol was evaporated; the residue was taken up in water (50 ml) and extracted with PhMe (2×50 ml). The combined extracts were fractionally distilled in a vacuum (5 mm Hg).
b. (R = C5H11, C6H13, C7H15). The reactants were mixed as above, and the mixture was brought to boiling until the reactants dissolved completely. Then it was cooled, washed with water to remove the acid, and fractionated in a vacuum. All the phenols obtained were recrystallized from heptane.
Preparation of AlI3
Dry aluminium foil (250 mg, 9.3 mmol) and iodine (1.9 g, 15 mmol) were refluxed in dry CS2 (10 ml) or dry CH3CN (8 ml) till the iodine color disappeared (~3 hr).
Cleavage of allyl phenyl ether in CH3CN
To a freshly prepared solution of AlI3 (5 mmol) in CH3CN, allyl phenyl ether (670 mg, 5 mmol) in CH3CN was added and the concentration of the solution was adjusted to approx. 1M with respect to both reagent and reactant. The reaction mixture was refluxed till there was no more starting material (5 hr. TLC), cooled and poured into water. The mixture was extracted with ether and the aqueous extract was washed with 5% sodium hydroxide solution. After acidification of the alkaline aqueous solution, it was extracted into ether, dried over anhydrous MgSO4 and the solvent was removed. The crude product after short path distillation yielded phenol; 418 mg (89%).
Cleavage of 1,3-benzodioxzole in CS2
Substrate | 1,4-Dimethoxybenzene | Product | 4-Methoxyphenol |
AlI3:Substrate | 1:1 (molar ratio) | Solvent | CS2 |
Reflux Time | 3 h | Yield | 74.2% |
To a freshly prepared solution of AlI3 (10 mmol) in CS2, 1,3-benzodioxole (610 mg, 5 mmol in CS2 (2 ml) was added and reflexed till there was no more starting material (7 hr. TLC). The cooled reaction mixture was decomposed with ice, extracted with ether and washed with thiosulphate solution. The thiosulphate solution was extracted once again with ether and the combined ether extract was dried over anhydrous MgSO4. The solvent was removed and the product was chromatographed (TLC silica gel; 3:1 hexane:ethylacetate) to obtain catechol, 440 mg (80%); m.p. 106°C.
The oxidation of 4-methoxybenzaldehyde to 4-methoxyphenol has also been performed with hydrogen peroxide with boric and sulfuric acids (yield 97%3) and with m-chloroperoxybenzoic acid (yield 92%4).
Chem. Abs. 95:61763
Hydroquinone monomethyl ether.
Pokrovskaya, I. E.; Parbuzina, I. L.; Gubenko, I. I. (USSR ). U.S.S.R. SU 825,487 (30 Apr 1981)
From: Otkrytiya, Izobret., Prom. Obraztsy, Tovarnye Znaki (16), 93 (1981) [Russian]
Hydroquinone (I) mono-Me ether was prepd. by treating I with a neutral soda mixt. of MeOH and H2SO4 at 90-100°C. In an improved procedure, the reaction was carried out in the presence 4-10 wt.% I di-Me ether, which was recycled.
Chem. Abs. 93:71276
Preparation of hydroquinone ethers.
Bellas, Michael; Cahill, Robert; Hayes, Leslie. GB 1,557,237 (5 Dec 1979), 8 pp.
The title ethers I [R = C1-C18 alkyl, (CH2)2OEt; R1 = H, C1-4 alkyl] were prepd. by reaction of a mixt. of the corresponding hydroquinone and benzoquinone (wt. ratio 5:1 to 20:1) with ROH in the presence of an acid dehydration catalyst. E.g., reaction of 0.67 g benzoquinone and 9.33 g hydroquinone with 50 mL MeOH in the presence 10 g conc. H2SO4 gave 80% I (R = Me, R1 = H).
Chem. Abs. 1:140564
Hydroquinone monoalkyl ethers.
(Eastman Kodak Co., USA). JP 54061132 (17 May 1979) 4 pp. [Japanese]
Ethers I (R = alkyl, R1 = H, alkyl; R2 = R3 = H or R2R3 = CH=CHCH=CH) were prepd. by esterification of I (R = H; R1-R3 as above) with alcs. ROH in the presence of benzoquinones II (R1-R3 as above) and acidic dehydrating agents. Thus, stirring I (R-R3 = H) in MeOH with benzoquinone and H2SO4 16 h gave 100% I (R = Me, R1-R3 = H).
Chem. Abs. 90:168271
p-Methoxyphenol.
Gubenko, I. I.; Kondrashova, M. F.; Manyashkina, V. M.; Medvedeva, S. P.; Parbuzina, I. L. (USSR). SU 643,489 (25 Jan 1979) From: Otkrytiya, Izobret., Prom. Obraztsy, Tovarnye Znaki (3), 84 (1979) [Russian]
p-MeOC6H4OH was prepd. by methylating hydroquinone with MeOH-H2SO4-Na2CO3 (1.3:1:1) at 90-100°C.
Chem. Abs. 89:208651
Solvent composition effects in reversed phase partition chromatography. I.
Phenols in systems of the type oleyl alcohol-water + acetone or water + acetonitrile.
Soczewinski, Edward; Waksmundzka-Hajnos, Monika; Chem. Anal. (Warsaw), 23, 429-35 (1978) [English]
The relation between RM values of 28 phenols and the concn. of Me2CO or MeCN in the aq. mobile phase was investigated; the stationary phase was Whatman no. 4 paper impregnated with C6H6 solns. of oleyl alc. In most cases the relations were linear, which permitted the detn. of the RM values beyond the range of optimum accuracy by extrapolation
Chem. Abs. 105:104738
Electrochemical synthesis of hydroquinone monoalkyl ethers.
Takamatsu, Hideki; Takakuwa, Yasuo; Tsuchiya, Shuji. Jpn. Kokai Tokkyo Koho JP 61064891 (3 Apr 1986) 4 pp.
Hydroquinones and alcs. are electrolyzed for monoalkylation to give hydroquinone monoalkyl ethers. The ethers, useful as intermediates for medicines, agrochems., dyes, etc., are obtained selectively at high yield. Thus, hydroquinone and was dissolved in EtOH and electrolyzed, using Pt electrodes, for 18 h at 30 V and ~30°C (12,000 C electricity) to give hydroquinone monoethyl ether at 86% conversion, 99% selectivity, and 85% yield. No byproduct (hydroquinone di-Et ether) was obtained.
Chem. Abs. 104:87782
Study of the steam distillation of phenolic compounds using ultraviolet spectrometry.
Norwitz, George; Nataro, Nicole; Keliher, Peter N.; Anal. Chem. 58, 639-41 (1986)
The steam distn. of 42 phenolic compds. was studied using a semimicro steam-distn. app. and UV spectrometry. In the distn., the following gave >95% recoveries: PhOH, 2-RC6H4OH (R = O2N, MeO, Br, Cl), 2,3- and 2,4-Cl2C6H3OH, 2,4,5- and 2,4,6-Cl3C6H2OH, 2,4-Br2C6H3OH, 2-, 3- and 4-cresol, 4,2-Cl(Me)C6H3OH, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-xylenol, 4-RCMe2C6H4OH (R = Me, Et), thymol and carvacrol. The percent recovery for the other phenolic compds. was as follows: 3-O2NC6H4OH, 3.7%; 4-O2NC6H4OH, 1.8%; 3-MeOC6H4OH, 31.1; 4-MeOC6H4OH, 23.2; 3-BrC6H4OH, 79.6; 4-BrC6H4OH, 67.8; 3-ClC6H4OH, 93.5; 4-ClC6H4OH, 91.6; 3,4-Cl2C6H3OH, 64.1; 2,4-(O2N)2C6H3OH, 21.2; picric acid, 0.0; 2-H2NC6H4OH, 0.1; 3-H2NC6H4OH, 0.2; 4-H2NC6H4OH, 0.1; pyrocatechol, 1.6; resorcinol, 0.4; hydroquinone (I), 0.0; pyrogallol, 0.7; and phloroglucinol, 0.1. Examg. the spectra of the undistd., distd. and residual solns. showed that the aminophenols undergo some decompn., and that I is almost completely destroyed during the distn. The important role that H bonding (intermol. and intramol.) plays in the recovery from steam distn. is examd
Chem. Abs. 97:91924
Monoalkyl ethers of hydroquinone and its derivatives.
Rivetti, Franco; Romano, Ugo; Di Muzio, Nicola US Pat. 4,469,897
The title compds. I (R = alkyl, R1 = H, alkyl) were prepd. by treating a hydroquinone I (R = H) with ROH in the presence of a transition metal salt. A mixt. of 1,4-(HO)2C6H4, MeOH, and CuCl2 under N2 kept 2.5-4 h at 105°C gave I (R = Me, R1 = H) in 87% selectivity with 55-85% conversion. Little or no etherification occurred in the absence of CuCl2.
Chem. Abs. 112:136225
Defense mechanisms of arthropods. Part 91. p-Methoxyphenol: chemical basis of stench of a female butterfly.
Eisner, T.; Eisner, M.; Jaouni, T.; Fales, H. M.; Naturwissenschaften, 77(1), 33 (1990) [English]
The female Great Southern White butterfly (Ascia manuste phileta) emits a potent phenolic stench when disturbed. The odor stems from a pasty secretion from the genitalia. GC-MS identified this defensive compd. as p-methoxyphenol.
Chem. Abs. 106:226806
Steam distillation of phenolic compounds in the presence of a large amount of sodium chloride.
Norwitz, George; Nataro, Nicole; Keliher, Peter N.; Microchem. J., 35(2), 240-3 (1987)
The steam distn. of phenolic compds. in the presence of a large amt. of NaCl was studied by use of a semimicro steam distn. app. and UV spectrometry. The recovery of many phenolic compds. in steam distn. was improved by the addn. of the NaCl, particularly in the case of 3- and 4-methoxyphenol, 3- and 4-bromophenol, and 3- and 4-chlorophenol (essentially complete recovery was obtained with the latter four compds.). The recovery with 2-chlorophenol was ~5% lower. The recovery with 2-nitrophenol was ~10% lower and the results tended to be erratic (probably because the NaCl affects the intramol. H bonding of this polar compd.). The addn. of NaCl did not improve the very low recoveries obtained with aminophenols and di- and trihydroxyphenols without NaCl. It is recommended that NaCl be used in the detn. of total phenolic compds. in waters in procedures that require a steam distn., since more complete recovery is obtained for the phenolic compds. that are likely to be found in waters.
Chem. Abs. 125:167560
Preparation of 4-alkoxyphenols from 1,4-dihydroxybenzene.
Saito, Toranosuke; Hirayama, Takumi; Sakaguchi, Shigeo. Kokai Tokkyo Koho JP 8151343 (11 Jun 1996) 5 pp.
4-HOC6H4OR (I; R = lower alkyl), useful as polymn. inhibitors for vinyl monomers, stabilizers for polyesters, and intermediates for drugs, agrochems, and, dyes are prepd. by addn. of H2O2 to a mixt. of 1,4-C6H4(OH)2 (II), ROH, and ³1 of I, HI, metal iodides, and alkali metal iodates followed by addn. of acid catalysts or by addn. of H2O2 to a mixt. of II, ROH, ³1 of HI, metal iodides, and alkali metal iodates, and acid catalysts. An aq. H2O2 soln. was added dropwise to a mixt. of II, MeOH, H2SO4, and I at 60°C over 3 h and the reaction mixt. was further stirred at 60-70° for 6 h to give a product contg. 87.3% I (R = Me), vs. 54% for a control using no I.
Chem. Abs. 125:86240
Methods for the preparation of hydroquinone monomethyl ether.
Teng, Dianhua; Li, Tongzhen; Ma, Shuqin. Huaxue Yu Nianhe, (2), 105-106 (1996) [Chinese]
A review with 9 refs. on different methods for prepn. of hydroquinone monomethyl ether with the emphasis on the methods using hydroquinone and methanol as raw materials, an acid as catalyst, and benzoquinone as co-catalyst
Chem. Abs. 124:260570
Process for the preparation of hydroquinone monoalkyl ethers.
Caproiu, Miron Teodor; Banciu, Anca Adriana; Olteanu, Emilia. RO 105,090 (1994), 5 pp. [Romanian]
The title ethers were prepd. by treating hydroquinone with an alc. in presence of an oxidizing agent and a dehydrating agent in the alc. as solvent, or using another solvent. Thus, hydroquinone was treated with MeOH, H2O2, and H2SO4 under reflux for 6 h to give 70.5% 4-Methoxyphenol of 98.7% purity.
Chem. Abs. 118:124199
Etherification of phenols with lower alcohols.
Uohama, Misao; Takahashi, Katsuji. Jpn. Kokai Tokkyo Koho JP 4305546 (28 Oct 1992) 6 pp.
Phenols are etherified with lower alcs. in liq. phases in the presence of acid catalysts with removing alkyl ethers together with unreacted alcs. and H2O by distn. Catechol and concd. H2SO4 were heated at 150°C with adding MeOH-catechol mixt. for 6 h to give 88.4% guaiacol
Chem. Abs. 127:81239
Process and catalysts for the production of alkyl ethers of phenols from phenols and alkanols.
Ariyoshi, Kimio; Satoh, Yuuichi; Saito, Noboru (Nippon Shokubai Co., Ltd., Japan). 16 pp. EP 781,751 (2 Jul 1997)
Alkyl ethers of phenols (e.g., anisole) are prepd. in high yield and selectivity by the etherification of a phenol (e.g., PhOH) with an alkanol (e.g., MeOH) in the presence of an oxide catalyst comprising a supported alkali metal (e.g., Cs) as a constituent element.
Process for the preparation of 4-alkoxyphenols
DE 3,207,937 (March 5, 1982)
A novel process for the preparation of 4-alkoxyphenols by reacting hydroquinone with an alcohol at increased temperatures in the presence of catalytic amounts of benzoquinone and an acid is characterised in that perchloric acid is used as the acid. This process gives 4-alkoxyphenols in high yields. 4-Alkoxyphenols are valuable intermediates, for example for the preparation of 4-alkoxyphenyl carboxylates, which are used as liquid-crystalline compounds.
