THE CHEMISTRY OF VITAMIN E. XXVIII. (1) SYNTHESIS OF THE

J. Org. Chem. , 1941, 06 (3), pp 427–436. DOI: 10.1021/jo01203a008. Publication Date: May 1941. ACS Legacy Archive. Cite this:J. Org. Chem. 06, 3, 4...
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THE CHEMISTRY OF VITAMIN E. XXVIII. (1) SYNTHESIS OF THE THREE DIMETHYLETHYLQUINONES LEE IRVIN SMITH

AND

J. W. OPIE

Received January 6, 19@

The three dimethylethylbenzoquinones were required in order to prepare a set of homologs of a-tocopherol. In preparing such trialkylbenzoquinones, it is not possible to start with benzene hydrocarbons having the three substituents in positions 1, 2, and 4, because the next substituent introduced practically always enters the 5 position. Consequently indirect methods must be used (2), and in a previous paper (2a) a general method has been described whereby quinones may be prepared readily and in good yields from the corresponding phenols. This method, when applied to the proper dimethylethylphenols, led to the dimethylethylquinones, but the synthesis of the phenols themselves in quantity from readily available material involved several steps. Von Auwers (3) in a very complete study of the Fries rearrangement, found that the acetate of 3 ,bdimethylphenol (I) and that of 2,3-dimethylphenol (111) rearranged to form the corresponding orthoacetophenols (11, IV) in good yields. He also found that these acetophenols could be

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LEE IRVIN S M I T a AND J. W. OPIE

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SYNTHESIS O F DIMETHYLETHTLQUINONES

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reduced to the corresponding dimethylethylphenols (V and VI) by the Clemmensen method. The methods of v. Auwers were used in preparing the phenols V and VI. Reduction of the aceto compounds I1 and IV was also carried out catalytically. KO difficulty was experienced in preparing these two phenols in amounts sufficient for preparation of the quinones I X and X by the standard procedure, viz., coupling the phenols with diazotized sulfanilic acid, cleaving the azo compounds to the amino phenols VI1 and VI11 and oxidifling the latter to the quinones. Karrer and Hoffmann (2b) have prepared I X from the corresponding phenol by oxidative hydrolysis of the p-nitrosophenol. However, the Fries rearrangement of the acetate of 2,5-dimethylphenol (XI) produces the para-aceto compound (XII) (323, 4) instead of the ortho-aceto compound XI11 and therefore it was necessary to prepare the third dimethylethylquinone, (XIV) from some other intermediate. The route to this quinone, starting with 2,8dimethylphenol, is shown on page 428. In addition to the preparation of the three quinones, this paper also includes a description of improvements in the preparation of 2,3-dimethylaniline ( 5 ) . The conversion of this amine into 2,S-dimethylphenol has been studied in some detail, and two procedures have been devised whereby this phenol is rendered much more readily accessible than heretofore. These are discussed in the experimental part. EXPERIMENTAL PART'

2,6-Dimethyl-S-ethylbenzoquinone(IX) 3,6-DimethyZphenylacetate (I) (249 g., 95% b.p. 118-120" under 19 mm.2) was prepared in the usual way from acetic anhydride (325 g.), and sulfuric acid (2 cc.). d-Hydrozy-4,6-dimethylacetophenone(11) (3, 6). Aluminum chloride (100 g.) was carefully added t o the cold (0') acetate I (61 g.) and the mixture was then warmed for ten hours on the steam-bath, decomposed, and steam distilled. The product, isolated from the distillate, when fractionated under 13 mm., was separated into a forerun (12 g., 17%) boiling a t 111-137", and I1 (47 g., 67%), which boiled a t 144", and which solidified to a light yellow solid that melted a t 57-58.5°.3 The forerun, consisting of a mixture of the acetate I and 3,5-dimethylphenol, was used in a subsequent preparation of I. When corrected for the recovered starting material (considered to be entirely I), the yield of I1 was 80%. 3,b-Dimethyl-8-ethylphenol (V). A. Clemmensen reduction of the hydroxy ketone I1 (32.8 g.) gave a mixture which was extracted with ether, washed well with water, and then extracted with aqueous potassium hydroxide (20%, 125 cc.). The alkaline extract was saturated with carbon dioxide to precipitate the phenol, which weighed 15 g. (50%) and melted a t 71-76'.' 1 Microanalyses by E. E. Renfrew, E. E. Hardy, and H. H. Hoehn. We wish to thank Dr. W. B. Renfrow, Jr., for checking certain of the experiments. * \'on Auwers and Borsche (6) give the b.p. as 120" (15 mm.). 8 Von Auwers and Borsche (6) obtained 60-70% yield of material that melted at 57-58' and boiled a t 140-141" (18 mm.). 4 Von Auwers and Borsche (7) give the m.p. as 80-81".

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LEE IRVIN SMITH AND J. W. OPIE

B. Catalytic reduction. The hydroxy ketone I1 (128 9.) was dissolved in alcohol (95%, 40 cc.), Raney nickel catalyst was added, and the ketone was shaken for three hours a t 175' under hydrogen (initial pressure, 2000 lbs. a t 25'). The contents of the bomb were poured into water and extracted with petroleum ether. The extract was filtered and shaken with Claisen's alkali. The alkaline solution was diluted with water, acidified, and extracted with ether. Removal of the solvent left a semisolid residue which, when crystallized from petroleum ether gave 77.4 g. (67%) of the phenol melting a t 79-80'. 4-Amino-5,6-dimelhyE-I?-ethylphenol(VII). The phenol V (77.4 g.) was coupled with diazotized sulfanilic acid (108 9.) according to the usual procedure (2). After the red solution had stood a t room temperature for twenty-four hours, sodium hydrosulfite (250 g.) was added and the mixture was heated and stirred for two hours. The color suddenly faded, and the amino phenol began to separate. The cooled (0") mixture was filtered. An analytical specimen of the amino phenol was prepared by recrystallizing a small portion twice from benzene. It formed white plates, and melted a t 158-159' with decomposition. Anal. Calc'd for C1~HIONO: C, 72.7; H, 9.1. Found: C, 73.0; H, 9.0. 2,6-Dimethyl-4-ethyZquinone (IX). The moist amino phenol from the above experiment was dissolved in hydrochloric acid (60 cc., 30%). Ferric chloride (400 g.) was added and the mixture was immediately steam distilled. The quinone, a golden yellow oil, was removed from the distillate by ether extraction. Bfter washing the ethereal solution thoroughly k i t h water, removal of the solvent left 56 g. (66%, based upon the phenol V) of the quinone, a golden yellow oil which boiled a t 111" under 10.5 mm. Anal. Calc'd for ClJL202: C, 73.17; H, 7.32. Found: C, 73.05; H, 7.59. Karrer and Hoffman (2b) obtained this quinone in 65% yield from the phenol, using the p-nitrosophenol as an intermediate. They report it also as a yellow oil. I?,6-Dimethyl-b-ethylhydroquinone.The quinone I X (10 g.) was dissolved in acetic acid (37 cc.) and water (27 cc.). Zinc (20 mesh, 9.2 g.) was added and the mixture was refluxed until i t became colorless. Boiling water (37 cc.) was added, and the hot solution was decanted from the zinc. The zinc was washed with another portion (37 cc.) of hot water, which was combined with the main solution. The solution was cooled (0") and the hydroquinone (8 g., 80%) was removed. It melted a t 153-153.5'; an analytical sample melting a t 158-158.5' was prepared by crystallizing a small portion (0.6 g.) from benzene. Anal. Calc'd for Cl&~,02: C, 72.40; H, 8.44. Found: C, 72.13; H, 8.61. Karrer and Hoffman (2b) report this hydroquinone to melt a t 157'. 9,8-Dimethyl-6-ethylbenzoquinone(X) 3-Amino-o-xylene. Catalytic reduction of the nitro compound (5)s to the amine results in much better yields than those obtained by the iron-acetic acid method previously described (5). 3-Nitro-0-xylene (300 g., b.p. 109-112" under 7 mm.) was shaken with Raney nickel in a 1-liter bomb under hydrogen a t an initial pressure of 1475 lbs. (25'). With the temperature controller set a t l l O o , the temperature (88"), forty minutes after the heater was turned on, rose rapidly during the next thirty minutes to 172' while the pressure dropped to 1300 lbs. A t this point the bomb 5 We wish to thank Dr. R. T. Major and Merck and Co., Inc., for a very generous gift of 3-nitro-o-xylene.

SYNTHESIS OF DIMETHYLETHYLQUINONES

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began to cool; twenty minutes later the temperature was 140' and the pressure was 925 lbs. The bomb was then reflled with hydrogen (1500 lbs.) and shaken at 140145" for half an hour longer, during which the pressure drop was only 100 lbs. The cooled bomb was washed out with ether, the water formed during the reaction waa separated, and the catalyst was a t e r e d off. After drying (Drierite), the ether was removed and the residue was distilled. The amine (251 g., 100%) boiled at 114' under 19 mm. 3-Iodo-o-xylene. The amine (251 g.) was added to a hot solution of sulfuric acid (190 cc.) in water (1500 cc.) and the mixture was boiled until the amine sulfate dissolved completely. The solution was then cooled and ice (800 g.) was added, causing the sulfate to reprecipitate as a granular solid. Sodium nitrite (150 g.) dissolved in water (500 cc.) was slowly added and the cooled mixture was allowed to stand until the solids had all dissolved. Then, a t 0", potassium iodide (350 g.) in water (450 cc.) was slowly added and the mixture was allowed to stand for twelve hours, gradually warming to room temperature, after which i t was heated on the steam-cone until no more gas was evolved. Sodium hydroxide (280 g.) in water (400 cc.) was added and the mixture was steam distilled. The heavy oil was extracted with ether from the distillate and the ether was removed. The residue of iodo compound weighed 294 g. (61%).6 The alkaline solution remaining from the steam distillation was acidified with sulfuric acid and again steam distilled, yielding 6 g. of impure 2,a-dimethylphenol. $,%Dimethylphenol. The above iodo compound (294 g.), copper wool (40 g.), and aqueous sodium hydroxide (160 g. in 850 cc. of water) were heated in a bomb. After three hours the temperature had reached 275", where i t was held for fifteen minutes to complete the reaction. The alkaline reaction-mixture was extracted with ether, and the aqueous layer was then acidified and steam distilled. Ether extraction removed 127 g. (79%) of 2,3-dimethylphenol from the distillate. The phenol melted at 65-69'.' The over-all yield of pure phenol from the amine was 55%. An alternative procedure, which avoids the preparation of the iodo compound, is given below. While the yield of phenol produced by this method is 52%, the product is much more difficult to purify than that obtained via the iodo compound, because large amounts of 4-methylindazole (?) are simultaneously formed. The amine (32 9.) was dissolved in boiling water (200 cc.) containing sulfuric acid (21.7 cc.). The solution was cooled, ice (250 g.) was added, and then sodium nitrite (20.7 9.) in water (100 cc.) was slowly dropped in with stirring. The mixture was stirred until all the solids had dissolved, after which it was allowed t o warm to room temperature and to stand for twenty-four hours. It was then steam distilled. The distillate was extracted with ether and the phenol was removed from the ether by extraction with sodium hydroxide (10%). The alkaline solution was saturated with carbon dioxide and extracted with ether. After removal of the ether, the phenol was distilled under 10 mm. The product boiled a t 91-94' and weighed 16.5 g. (52%). The residue from the steam distillation deposited a considerable quantity of long needles, probably 4-methylindazole, 2,.??-DimethylphenyZ acetate (111). 2,3-Dimethylphenol (127 9.) was converted into the acetate (154.5 g., 9573, which boiled a t 112-113' under 12.5 mm., 104' under 8 mm.8 2-Hydroxy-3,4-dimethylacetophenone (IV). The acetate I11 (34 g.) was rearranged Klages and Liecke (8) give the b.p. as 125-126' (15 mm.). Tohl (9) reported 2,3-dimethylphenol to melt at 75". 8 Von Auwers and Mauss (3b) give the b.p. as 226-228'.

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LEE IRVIN SMITH AND J . W. O P I E

by aluminum chloride (51 9.) giving the ketone IV (23.4 g., 69%), a yellow liquid which boiled a t 120-124" under 8 mm., 127-129" under 10.5 mm.9 A semicarbazone was prepared, which, after crystallization from ethyl acetate, melted a t 247" with decomposition. Anal. Calc'd for C11HlsNa02: C, 59.73; H, 6.78. Found: C, 60.00; H, 6.84. Z,b-Dimethyl-6-ethylphenoZ(VI). The ketone IV (15 g.) was reduced by the Clemmensen method. The reaction-mixture was steam distilled and the distillate was extracted with ether. The ether was replaced by petroleum ether, and the solution was extracted with Claisen's alkali. The alkaline extract was diluted with water, acidified, and extracted with ether. Removal of the solvent left the phenol (10 g., 7401,) which melted a t 52-53". V. huwers and Mauss (3b) give the melting point as 53-54". Catalytic reduction of the ketone (98.4 9.) using a copper chromite catalyst, a temperature of 200", and an initial hydrogen pressure 1300 lbs., gave the phenol VI (78 g., 87%) which melted a t 50-52". 4-Amino-~,d-dimethyl-6-ethylphenol (VIII). The phenol VI (11.5 g.) was coupled with diazotized sulfanilic acid (15.6 g.) as described for VI1 above. After standing for twenty-four hours, sodium hydrosulfite (75 g.) was added and the mixture was stirred and heated until the orange color faded. The amino phenol was filtered from the cooled solution, and a small portion of it was crystallized five times from benzene. The product formed light brown needles which melted a t 138-139" with decomposition. Anal. Calc'd for ClOH16NO: C, 72.7; H , 9.15. Found: C, 73.0; H, 9.0. 2,9-DimethyZ-6-ethylquinone(X). The moist amino phenol VI11 was oxidized to the quinone by treatment with ferric chloride as described for IX. The quinone formed a yellow solid which weighed 10.7 g. (86% based upon the phenol VI) and which melted a t 37-38' and boiled a t 111' under 9 mm. Anal. Calc'd for CloHlsO,: C, 73.17; H, 7.31. Found: C, 73.07; H, 7.48. I,S-Dimethyl-6-ethylhydroquinone.The quinone X (14 g.) was reduced with zinc (15 g.), acetic acid (60 cc.), and water (45 cc.) as described above for the reduction of IX. The crude product (12 g., 85%) melted a t 160-161". An analytical sample, prepared by crystallizing a small portion of the product from benzene, melted a t 160-160.5". Anal. Calc'd for C1d-I1,02: C, 72.28; H, 8.43. Found: C, 72.34; H, 8.46. d,6-Dimethyl-6-ethylbenzoquinone(XIV) p-Xyloquinone (56 g., 82%) was prepared from 2,5-dimethylphenol (61 g.) by coupling the phenol with diazotized sulfanilic acid as described previously (2), but the yield of quinone was greatly improved by reducing the azo compound with sodium hydrosulfite (150 g.) as described above. A small portion of the intermediate 4-amino-2,5-dimethylphenol, crystallized from dioxane darkened a t 220", softened a t 238O, and melted at 241' (decomp.). Anal. Calc'd for CsHIINO: C, 70.03; II, 7.90. Found: C, 69.83; H, 8.06. The moist amino phenol was dissolved in a slight excess of hydrochloric acid, ferric chloride (400 g.) in water (300 cc.) was added, and the mixture was steam disOVon Auwers and Mauss (3b) give the b.p. as 122-124" (12 mm.).

SYNTHESIS OF DIMETHYLETHYLQUINONES

433

tilled. The distillate was chilled and the yellow quinone was filtered off. It melted a t 123-125'. A portion of the quinone (4 g.) was reductively acetylated by boiling it for thirty minutes in acetic acid (10 cc.), acetic anhydride (20 cc.) t o which had been added zinc (10 g., 20 mesh) and sodium acetate (1 g.). The mixture was poured into water, then made basic with ammonium hydroxide and extracted with ether. The product (1 g.), after crystallization from ligroin and chloroform, melted a t 133-134". Curiously, this diacetate of p-xylohydroquinone does not appear to have been described before. Anal. Calc'd for C12H1404: C, 64.86; H, 6.45. Found: C, 65.29; H, 6.58. This reductive acetylation gives very poor results when i t is applied to any but very small amounts of the quinone. l,d-Dimethoxy-d, b-dimethylbenzene (XV). p-Xyloquinone, prepared as above from p-xylenol (31 g.), was reduced to the hydroquinone with zinc and acetic acid, as described for the reduction of quinones IX and X. The crude hydroquinone was dissolved in methanol (100 cc.), methyl sulfate (50 cc.) was added, and the solution was vigorously stirred under reflux while a saturated solution of potassium hydroxide in methanol was carefully added. When the solution became strongly basic, more methyl sulfate (50 cc.) was added slowly, followed by the base, then more methyl sulfate (50 cc.) and again the base until the mixture was strongly basic. The dimethoxy compound can be isolated by steam distillation, but this operation is very tedious when large amounts of material are involved and it was found better to add water, filter off the product, and purify i t either by distillation or crystallization from methanol. The product (32 g., 78% based upon the original phenol) obtained in this experiment boiled a t 118-120" under 9 mm., and melted a t 108" in agreement with the value in the literature (10). 1,~-Dimethoxy-S,6-dimethyl-b'-bromobenzene (XVI). The dimethyl ether XV (20 g.) was dissolved in carbon tetrachloride (30 cc.) and to the warm solution was rapidly (15 minutes) added a solution of bromine (20 9.) in carbon tetrachloride (40 cc.). There was a short induction period, after which the reaction proceeded quite regularly. The solution was washed, first with water, then with bisulfite (20%) followed by sodium hydroxide (10%). The solvent was removed and replaced by petroleum ether and this solution was extracted with Claisen's alkali and then washed with water. The yield of bromo compound (m.p., 51-54') was 26 g. (88%). An analytical sample, melting a t 59-60", was prepared by crystallizing 0.5 g. of the material from methanol. Anal. Calc'd for Cl&sBr02: C, 48.98; H, 5.31. Found: C, 49.65, 49.23; H, 5.49, 5.65. d,6-Dimethyl-S,6-dimethoxybenzaldehyde(XX). The dimethyl ether XV (3.32 g., 0.02 moles) was dissolved in benzene (20 cc.), zinc cyanide (3.5 g.) was added and the mixture was vigorously stirred while a rather rapid stream of hydrogen chloride was passed through i t for an hour. The yellow solution was cooled and aluminum chloride (4.0 g.) and more benzene (15 cc.) were added. The stream of hydrogen chloride was continued for two hours longer. After standing for one hour, more zinc cyanide (0.7 g.) was added and the gas was passed through the vigorously stirred mixture for another hour. The mixture was then warmed to 40-50" for two hours while stirring and introduction of hydrogen chloride was continued. After standing overnight, hydrochloric acid (50 cc., 15%) was added and the mixture was refluxed for thirty minutes and then steam distilled. The distillate, containing the benzene and a white solid (which rapidly turned orange in the light) was extracted with ether.

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LEE IRVIN SMITH AND J.

W. OPIE

The solvents were removed from the combined extracts, and the residue (3 g.), an orange solid, was crystallized from methanol. It then melted. a t 51-53". For analysis, a small sample was crystallized twice more from methanol, when it melted at 55-56'. Anal. Calc'd for CllHlrOa: C, 68.04; H, 7.22. Found: C, 68.37; H, 7.34. Semicarbazone. The aldehyde (1 g.) was dissolved in a little methanol, water was added until the solution became cloudy and then the cloudiness was removed by addition of methanol. Semicarbazide hydrochloride (1 g.) and sodium acetate (1.5 g.) were added. The semicarbazone started to crystallize at once. More methanol and water were added and the mixture was boiled for ten minutes and then chilled. The product was removed and crystallized from methanol, when i t melted a t 216-217'. Anal. Calc'd for ClaH1,NsOa: C, 57.37; H, 6.77. Found: C, 57.16; H, 6.77. 8,6-Dimethyl-5,6-dimethoxyphenyl methyl carbinol (XIX). A. From the aldehyde XX. The aldehyde (5 g., 0.027 moles) in dry ether (25 cc.) was added t o a solution of methylmagnesium bromide (prepared from methyl bromide (5 g.), magnesium (0.65 g.), and 25 cc. of ether). An orange precipitate formed immediately, but as the reaction proceeded, this gave way to a white granular precipitate. The mixture was refluxed for a few minutes and was then poured into iced ammonium chloride solution. The ether layer was removed and the aqueous layer was extracted three times with ether. The combined ether solutions were atered, the solvent was distilled off and the residue, an oil (5 g.), was distilled. It boiled a t 140-160" under 8 mm., and weighed 3.5 g. Anal. Calc'd for C12HlsOs: C, 68.57; H, 8.57. Found: C, 68.38; H, 8.90. The above material was subjected for four hours t o the action of hydrogen under 2650 lbs. a t 175" in the presence of Raney nickel, but no reduction occurred. The product was a n oil which boiled a t 154-156' under 8 mm., and i t was unchanged XIX as shown by the analysis. Anal. Found: C, 68.74; H, 8.76. B. From the bromo compound XVI. The bromo compound (41.5 g.), and ethyl bromide (18.5 g.) in ether (175 cc.) were added slowly and with stirring to magnesium turnings (8.25 g.). The reaction was slow in starting, but proceeded vigorously once i t was under way. After the addition was complete (30 minutes) the mixture of solution and white precipitate was refluxed and stirred for three hours. Considerable metal remained undissolved. The mixture was cooled (0') and a solution of freshly distilled acetaldehyde (30 g.) in ether (40 cc.) was slowly added. After the vigorous reaction was over, the mixture was stirred and refluxed for thirty minutes and then allowed t o stand overnight. After decomposition of the reactionmixture with dilute acetic acid, the ether layer was removed, washed with water and dried (Drierite). The residue was fractionated under 8 mm. through a short packed column and gave (A) a forerun (4 g.) mostly solid, boiling up to 137', and (B) a liquid fraction (22 g.) boiling a t 137-156'. Refractionation of (B) gave only 6 g. of material with the boiling point 154-156'; most of this fraction boiled at 137-153'. Considerable resinous material remained in the distillation flask. 8,6-Dimethyl-5,6-dimethoxystyrene(XXI). A drop of sulfuric acid was added to the above carbinol (6 g.) and the mixture was distilled under 8 mm. Water came over first, followed by a colorless liquid which boiled at 125-126'. A drop of sulfuric acid was added to the low-boiling material from fraction (B) above and from this

SYNTHESIS OF DIMETHYLETHYLQUINONES

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mixture more of the styrene boiling a t 125-126' was obtained. A similar treatment of the resinous residue from (B) above gave still more of the styrene. Redistillation of the combined styrene fractions gave 16.3 g. of material which boiled a t 125-129' under 8 mm., and which was regarded as XXI although the analytical values were poor. 1,4-Dimethoxy-W, 6-dimethyl-6-ethylbenzene (XVII). A. From the bromo compound XVI. The bromo compound XVI (11.5 g.) was dissolved in dry ether (60 cc.) and the solution was placed in a three-necked &ask equipped with reflux condenser, stirrer, and dropping-funnel. Magnesium (3.64 g.) and a crystal of iodine were added, the stirrer was started, and ethyl bromide (5.12 g.) in ether (30 cc.) was slowly (thirty minutes) dropped into the mixture. The reaction was brisk but easily controlled. After all the ethyl bromide had been added, the mixture was refluxed gently for four hours. A t the end of this time the product was a pasty mass. Ethyl sulfate (39 g.) dissolved in ether (50 cc.) was added slowly (one hour) and with stirring. The mixture was refluxed for one hour longer and then was set aside for twelve hours. Iced ammonium chloride was added and the ether layer was removed and washed six times with sodium hydroxide (10%) followed by one washing with water. Removal of the ether left an oil (10 g.) which partially solidified in a bath of acetone and dry ice. The solid (m.p. 100-106", XV) was iiltered from the cold mixture and the filtrate was distilled under 8 mm. from a Hickman still. The first fraction (1.1 9.) boiled a t 100-106" and was XV. The second fraction (3.7 g.) boiled a t 125128" and was the dimethoxy compound XVII. Repetition of this experiment, starting with 54 g. of the bromo compound XVI, gave 24.1 g. (56%) of the dimethoxy compound XVII boiling a t 136139.5" under 19 mm., but a considerable residue, which apparently was also XVI, could not be distilled out because of the design of the still (see below). The substance was not pure, however, for the analytical values were poor. Rather than risk the losses involved in handling this liquid any further, it was converted directly to the quinone XIV. B. From the vinyl compound XXI. The vinyl compound XXI (16 9.) was not reduced when its solution in an equal volume of ethanol was subjected to the action of hydrogen under 1800 lbs. pressure a t 200" in the presence of a copper chromite catalyst. The catalyst was converted to a red powder which was removed, fresh catalyst was added, and the experiment was repeated, but the result was the same. The substance was then recovered (11.4 g.) and the recovered material, in an equal volume of ethanol, was subjected to the action of hydrogen in the presence of Raney nickel. Reduction was rapid a t 50" under 1000 lbs. pressure. The product, on fractionation, gave 9.8 g. of the dimethoxydimethylethyl compound XVII which boiled a t 119-120" under 8 mm. I n view of the obvious impurity of this specimen, i t was not analyzed but was converted directly to XVIII and the quinone XIV. d,6-DimethyZ-6-ethyZquinone (XIV). The dimethyl ether XVII (24.1 g.) was refluxed for one hour in acetic acid (320 cc.) containing hydrobromic acid (48%, 240 cc.). Ice was added and the mixture was extracted with ether. After washing the ether layer four times with water, the ether was evaporated and the residue was added to excess ferric chloride solution and steam distilled. The distillate was extracted with ether, the ether solution was washed with water and dried. Removal of the ether left the quinone as a golden yellow oil. The residue left in the still after removal of XIV (see above) wasl put through a similar treatment. The combined quinone weighed 24 g. (73% based upon 54 g. of bromo compound XVI). Anal. Calc'd for C1oHIzO~: C, 73.17; H, 7.31. Found: C, 73.12; H, 7.74. W,6-Dimethyl-6-ethy2hyd709uinone(XVIII). The quinone XIV (24 g.) was dis-

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LEE IRVIN SMITH AND J. W. OPIE

solved in acetic acid (100 cc.) and water (75 cc.) and reduced by boiling the solution with zinc (20 mesh, 24 g.) aa described for the reductions of the other quinones. The product (22.5 g., 93%) melted at 158-159". A small portion, crystallized from benzene, melted at 161-163". Anal. Calc'd for CloHllOa: C, 72.29; H, 8.43. Found: C, 72.38, 72.02; H, 8.80, 8.70. SUMMARY

1. The syntheses of the three dimethylethylquinones have been described. 2. The paminophenols corresponding to these quinones have been prepared. 3. Improvements in the preparation of 2,3-dimethylaniline, and the conversion of this amine into 2,3-&methylphenol have been described. MINNEAPOLIS,MINN. REFERENCES (1) Paper XXVII, J. Org. Chem., 6, 236 (1941). J. Org. Chem., 4, 318 (1939) (2) (a) SMITH,OPIE, WAWZONEK,AND PRICHARD, (b) KARRER AND HOFFMANN, Helu. Chim. Acta, 22, 654 (1939). (c) KARRER AND HOFFMANN, Helu. Chim. Acta, 23, 1126 (1940). (3) (a) VON AUWERS, BUNDESMANN, AND WIENERS, Ann., 447, 162 (1926). (b) VONAUWERSAND MAUSS,Ann., 460, 240 (1938). (c) VONAUWERSAND JANSSEN, Ann., 483, 44 (1930). (4) BLATT,Chm. Rev., 27, 421 (1940). (5) EMERSON AND SMITH,J. A m . Chem. SOC.,62, 141 (1940). Ber., 48, 1698 (1915). (6) VON AUWERSAND BORSCHE, (7) VON AUWERS AND BORSCHE, Ber., 48, 1716 (1915). (8) KLAGES AND LIECKE, J . prakt. Chem., (2) 61,323 (1900). (9) T ~ H LBer., , 18, 2562 (1885). (10) XOELTING AND WERNER, Ber., 23, 3252 (1890).