CLV.-The Oxiclation of Monohyd& Phenols with Hydcrogen Peroxide

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THE OXIDATION OF MONOHY DRIC PHENOLS. 1659 Published on 01 January 1910. Downloaded by University of Illinois at Chicago 03/02/2015 08:14:15.

CLV.-The Oxiclation of Monohyd& Phenols with Hydcrogen Peroxide. By GEORGEGERALD HENDERSON and ROBERTBOYD, B.Sc. (Carnegie Research Scholar). HAVINGoccasion to prepare some dihydric phenols of the formula, C,,H,,(OH),, we endeavoured to find a simpler and more direct method of obtaining these compounds from monohydric phenols than those which are usually employed. To begin with, we applied to thymol the process of oxidising monohydric phenols in alkaline solution with potassium persulphate, which is stated to work well with the lower members of the series, but the results were not satisfactory, Equally disappointing results attended our trials of View Article Online

1660 HENDERSON AND BOYD: THE OXIDATION OF

the method of oxidation with dilute solutions of hydrogen peroxide, but the use of Merck’s “ perhydrol,” a 30 per cent. aqueous solution of hydrogen peroxide, led to the attainment of the desired end. A number of monohydric phenols of the benzene series were treated with this reagent, glacial acetic acid being used as a solvent for the phenol, and all were found to undergo oxidation more or less easily, either in t?he cold 01- when moderately heated. The product was either a quinone, from which, of course, the corresponding dihydric phenol could be obtained by reduction, or a dihydric phenol, or, in one or two cases, a tetrahydric phenol. The following is a statement of the phenols examined and of the products obtained from them under the conditions described below. Thymol gave a very good yield of thymoquinone, along with a small quantity of a new tetrahydric phenol, tetraJcydr*ox~c~me?i?e, C,MePrS(OH),, a, colourless, crystalline solid, melting at 168O. Carvacrol gave the same products as thymol, in approximately the same relative proportions. 3 : 5-Diethylphenol, C,H,E&-OH, gave, apparently as sole product, the corresponding 3 : 5-dietJ~?/Z-p-beizzop~inone,C,H,Et,Oz, golden- yellow needles, melting at 36O, from which, by reduction with sulphurous acid, the dihydric phenol, 3 : 5-dietlT~ylquinoZ, C,H,Et,( OH),, was obta.ined in colourless crystals, melting at 114O. p-Nitroso-3 : 5-diethyZpJ~enoZwas also prepared. It forms pale yellow crystals, melting at 136O, and on reduction and subsequent oxidation yields diethyl-p-benzoquinone. p-tert.-Butylphenol, CsH4(CMe3)*OH, gave a new tetrahydric phenol, t etrahydroq-tert .-b utylb cnzcne, CGH(CMe,)(OH),, which crystallises in slender, colourless needles, melting at 138O. Phenol gave quinol, a little p-benzoqdinone, and a little catechol ;

Published on 01 January 1910. Downloaded by University of Illinois at Chicago 03/02/2015 08:14:15. no resorcinol was found. o-Cresol gave toluquinol (2 : 5-dihydroxytoluene) and some toluquinone ; m-cresol gave toluquinol, some toluquinone, and a little orcinoI ; and p-cresol gave homocatechol (3 : 4-dihydrosytoluene) ; no other product was found. The character of the oxidation products obtained depended, in the first place, on the constitution of the phenol oxidised, and, in the second place, on the conditions of the experiment, namely, the proportion of perhydrol used, the concentration of the acetic acid solution, the temperature, and the time. As regards the first point, it was found that monoliydric phenols, in which the p-position relative to the hydrosyl radicle is unoccupied by a radicle other than hydrogen, are more or less easily attacked by hydrogen peroxide even at the ordinary temperature, and that the product of oxidation is mainly a quinone, or a p-dihydric phenol, or a mixture View Article Online

MONOHPDRIC PHENOLS WlTH HYDROGEN PEROXIDE. 1661

of both, according to the conditions under which the reaction is carried out. On the other hand, those monohydric phenols in which the p-position relative to the hydroxyl group is occupied are osidised with greater difficulty, and a higher temperature is necessary; in such cases the product is usually a dihydric phenol con- taining the hydroxyl groups in the o-position with respect to each other. The lower members of the series tend to give tarry products more easily than the higher members, and it is best to use a larger proportion of the solvent (acetic aoid) when the former are being oxidised. We have also examined the action of perhydrol on smne cyclic hydrocarbons. In each case the hydrocarbon was mixed with perhydrol, sufficient acetic acid to €orm a clear solution was added, and the liquid was left for some time at the ordinary temperature or gently heated. The inembers of the benzene series which were used, namely, benzene, toluene, 1 : 3-diethylbenzene, and cymene, did not appear to react at all easily with the oxidising agent, but naphthalene, anthracene, and phenanthrene were readily oxidised, yielding phthalic acid, anthraquinone, and phcnanthraquinone respectively. The course of the preparative work invoIved in this investigation led us to attempt to prepare higher dihydric phenols directly by condensing quinol and resorcinol with diethyl ether in presence of anhydrous aluininium chloride. These experiments were unsuccessful, but we found that phenol could be condensed with methyl propyl ether, yielding a substance which appears to be a methylpropyl- phenol, C,H3MePr-OH. We intend to continue to study the behaviour of hydrocarbons towards perhydrol, and also to extend our experiments to

Published on 01 January 1910. Downloaded by University of Illinois at Chicago 03/02/2015 08:14:15. derivatives of phenols and to phenols other than those of the benzene series. EXPERINENTAL. According to a patented process (D.R.-P. 81068 and 81298), dihydric phenols of the benzene series can be obtained on the manufacturing scale from monohydric phenols by means of potassium persulphate. The persulphate is added in small portions to a dilute alkaline solution of the phenol, and the liquid is kept for one or two days at the ordinary temperature, or at 40°. When the reaction is finished, the solution is saturated with carbon dioxide, any unchanged phenol is distilled off in a current of steam, the residual liquid is acidified with dilute acid and then boiled, and finally the dihydric phenol which has been formed is extracted with ether. If the p-position relative to the hydroxyl group in the monohydric phenol is free, a p-dihydroxy-compound is obtained, View Article Online

1662 HENDERSON AND BOYD: THE OXlDATlON OF

but if the p-position is occupied, the product contains two hydroxyl groups in the o-position with respect to each other. Thus, phenol yields quinol, whilst p-cresol yields homocatechol. As the process appeared to be a pra.cticable one, we applied it in the prescribed manner to the oxidation of thymol, but found that with that compound the reaction does not proceed smoothly, as in the case of lower phenols. Much of the thymol remained unattacked, whilst the rest was mainly converted into a tarry substance, from which it was scarcely possible to separate any definite oxidation product. Various modifications of the process were tried-such as keeping the mixture cool with ice; adding the persulphate to a solution of thymol in the least possible quantity of alkali, and maintaining the mixture slightly alkaline by addition of sodium carbonate from time to time; agitating a mixture of thymol with aqueous potassium persulphate for several days, both at the ordinary temperature and at 60°-but with no improvement in the results. A dilute solution of hydrogen peroxide, either with or without the addition of a small quantity of an iron salt., has frequently been used as an oxidising agent, and, according to Martinoil (BUZZ. SOC. chim., 1885, [ii], 43, 155), when dilute aqueous hydrogen peroxide is gradually added to pure phenol in the cold, and the liquid is subsequently heated to 90°, oxidation of the phenol takes place, and a mixture of quinol, p-benzoquinone, and catecho1 is obtained. With thymol, however, we found this process also to be unsatisfac- tory; using ordinary '' ten volume " hydrogen peroxide, according to Martinon's method, very little of the thymol wits attacked, even when the mixture was heated. It then occurred to us to try a stronger solution of hydrogen peroxide, and this led to success. It Published on 01 January 1910. Downloaded by University of Illinois at Chicago 03/02/2015 08:14:15. was found that thymol and other monohydric phenols, when dissolved in glacial acetic acid, are more or less readily oxidised by perhydrol, with the results described in the following pages. Oxidation of Thyrno~?ur'tli PerhydroL-Seventy-five grams of thymol (1 mol.) were mixed with 190 C.C. of perhydrol (about 2 mols.), sufficient acetic acid was added to hold the thymol in solution, and the mixture was kept at the ordinary temperature. After a week or two, a small quantity of a colourless, crystalline solid had separated from the solution. The solid was collected, and water was gradually added to the filtrate until no further pre- cipitation took place. The yellow, crystalline precipitate was agitated with dilute sodium hydroxide, when only a small part passed into solution, and the undissolved portion was collected, washed with water, and dried. The golden-yellow crystals obtained in this way melted at 45*5O, and were identified as thymoquinone. View Article Online

MOKOHYDRIC PHENOLS WITH HYDROGEN PEROXIDE. 1663

A small additional quantity of thymoquinone was obtained from the mother liquor by steam distillation. Only a little of the thymol remained unoxidised. The alkaline solution with which the thymoquinone had been washed gave, on acidification, a precipitate of a, crystalline compound, which proved to be identical with the substance which had crystallised from the original acetic acid solution. After purification by recrystallisation from dilute alcohol, it was dried and analysed : 0.1562 gave 0.3460 CO, and 0.0947 H,O. C = 60.4 ; H = 6.7. 0.1544 ,, 0.3399 CO, ,, 0.0992 H,O. c"=60*1; H=7.1. C,,H,,O, requires C = 60.6 ; H = 7.1 per cent. Tctl.ull,?/dl.o~ycyme?ze,C,MePrP(OH),, so obtained, forms small, colourless crystals, which melt at 168O. If exposed to the air in it moist state, it, begins to turn yellow. It is rather sparingly soluble in cold water, readily so in alcohol, ether, chloroform, or glacial acetic acid. It dissolves with ease in solutions of alkali hydroxides, and the colourless liquid quickly begins to acquire a brown coloration in contact with air. In an aqueous solution, ferric chloride produces a bulky, red precipitate. The chief product of the oxidation of thymol by perhydrol is thymoquinone, whilst tetrahydroxycymene is only formed in small proportion. Very little tarry matter is produced. Me Me Me

Oxidation of Camacrol with Perhydrol.--The oxidation was carried out in the same way as in the case of thymol, and, as was Published on 01 January 1910. Downloaded by University of Illinois at Chicago 03/02/2015 08:14:15. to be expected, the result was precisely similar. The chief product was thymoquinone, and, in addition, a small quantity of tetrahydroxycymene was formed. Only a little tarry matter was produced, and almost all the carvacrol was oxidised. Are Me Me

Oxidation of 3 : 5-Diethylphenol with Perliydrol.-The diethylphenol required for this experiment was prepared by Jannasch and Rathjen's method (Ber., 1899, 32, 2392), which gave a satisfactory yield. The diethylphenol was oxidised with perhydrol in the same way ils thymol. When the reaction appeared to be completed, the View Article Online

1664 HENDERSON AND BOYD: THE OX1I)ATION OF

solution was diluted with water, and the yeIlow crystals, which separated after some time, were cdlected and purified by crystallisation from dilute alcoli~~l.Examination of the properties of the compound showed it to be 3 : 5-diethyLp-bencoquinone, C6H2Et202,which, for purpclses of comparison, we had already prepared by another mcthod described below. The filtrate was neutralised with sodium carbonate and agitated with ether, the ethereal solution was wa.shed and dried, and after removal of the ether by distillation a dark red, oily residue was obtained. The oily substance was sha.ken up with water, and after a short time the greater part solidified. The crystals were collected and drained on a porous plate, and, after recrysta.llisation, proved to be a further quantity of diethyl-p-benzoquinone. The small quantity of oily matter which was produced along with tlie quinone was not further esaxined. Kt Et

Diethyl-p-benzoquinone was also prepared from diethylphenol by a less direct method. p-A'it TOSO-3: 5-diethylpk e 12 ol, 0 :C,H,E t,: NOH (dietAyZ-p-b enso- puinoneoxime), was first obtained as follows. Diethylphenol was dissolved in alcohol previously saturated with hydrogen chloride, the solution was cooled with ice, and a cooled concentrated aqueous solution of the calculated quantity of sodium nitrite was slowly added. The dark green liquid obtained in this way was poured into water, when a yellowish-brown solid was precipitated. The precipitate was collected, washed with water, dried, washed with a

Published on 01 January 1910. Downloaded by University of Illinois at Chicago 03/02/2015 08:14:15. little chloroform, and recrystallised from dilute alcohol. It forms small prisms of a pale yellow colour, which melt and decompose at 136O. It is readiy soluble in alcohol, and almost insoluble in water : 0.1940 gave 13 C.C.N2 a.t 15O and 760 mm. N- 7.84. 0.3920 ,, 26.4 C.C. N, at 20O and 760 mni. N=7.7. C,,H,,O,N requires N = 7.8 per cent. 3 : 5-Bicthyl-p-7)encopinone, O:C,H,Et,:O, was prepared from nitrosodiethylphenol in the following manner. Five grams of the nitroso-compound were dissolved in 50 grams of 10 per cent. a.mmonia, and the solution was saturated with hydrogen sulphide. The reduction product, p-aniinodiethylphenol, was precipitated as a white solid, which was collected and washed with water. The precipitate was dissolved in 130 C.C. of 3 per cent. sulphuric acid, and 100 C.C. of water and 50 C.C. of a 10 per cent. solution of potassium dichromate were added. After about half an hour, the precipitate View Article Online

MONOHYDRIC PHENOLS WITH HYDROGEN PEROXIDE. 1665

which had formed was collected and dissolved in glacial acetic acid, and small quantities of chromic anhydride were added to the solution from time to time until the oxidation was completed. The quinone was then precipitated with water, collected, washed with water, and purified by crystallisation from dilute alcohol. It forms slender needles of a golden-yellow colour, which melt at 36O. If it is allowed to separate slowly from solution, crystals several centimetres in length may be obtained. It is only slightly soluble in water, but easily so in alcohol or ether, and it volatilises readily in a current of steam : 0.1967 gave 0.5294 CO, and 0.1240 H,O. C=73*4; H=7*0. C,,H,,O, requires C = 73.2 ; H = 7.3 per cent. The corresponding dihydric phenol, 3 : 5 - dietlzylquinol, C,H,Et2( OH),, was prepared by reduction of the quinone with sulphurous acid. The quinone was gently warmed with aqueous sulphurous acid until all the solid had passed into solution, and the reduction appeared to be completed. The phenol was then extracted with ether, and the ethereal solution was washed with water, dried, and concentrated to small bulk. On cooling, the phenol separated in small, colourless crystals. It melts at 114*, and is fairly easily soluble in water, and readily so in alcohol or ether. A solutiou in alkali hydroxides is at first colourless, but quickly turns brown on exposure to air. In aqueous solution the phenol is readily oxidised by ferric chloride, yielding the quinone : 0.2707 gave 0.7145 CO, and 0'2073 I3,O. C = 72.0 ; H = 8.6. C,,H,,02 requires C = 72.3 ; H = 8.4 per cent.

Oxidat ion of p-ter t .-Bu t y Zph eno I, C,H, (CMe,) 010H, wit ii Per- hydi-oZ.-The phenol required for this experiment was prepared

Published on 01 January 1910. Downloaded by University of Illinois at Chicago 03/02/2015 08:14:15. from tert.-butylbenzene. Nitration of the hydrocarbon yielded a mixture of the solid y- with some of t.he liquid o-nitro-derivative. The pnitro-compound was separated and reduced by means of tin and hydrochloric acid. The oily p-amino-compound was diazotised, and on distilling the solution with steam, a satisfactory yield of the phenol was obtained in lustrous needles, which melted at 9So (com- pare Studer, BEI'.,1881, 14, 1472). Five grams of the phenol were mixed wit11 10 grams of perhydrol and the quantity of acetic acid required to form IL clear solution. In this case the reaction appeared to proceed very slowly at the ordinary temperature, hence the solution was heated at about GOo for several days, and then neutralised with sodium carbonate and agitated with ether. The ethereal solution was washed with water, dried, and after removal of the ether by distillation, a white, solid residue was left, which was recrystallised from dilute alcohol. The substance thus obtained was found on analysis to be tet9-ahydroxp View Article Online

1666 HENDERSON AND BOYD: THE OXIDATION OF

tert.-bzctylb enzen e, C,H(CMe3) (OB),. It crystallises in slender, colourless needles, which melt at 138O. It dissolves rather sparingly in water, but freely in alcohol or ether axd in solutions of alkalis. Ferric chloride does not produce a coloration in an aqueous solution. The probable constitution of the compound is shown by the formula

0.1179 gave 0*2602 CO, and 0.0764 H,O. C= 60.2 ; H = 7.2. ClOHl4O4requires C = 60.6 ; H = 7.1 per cent. From the mother liquor from which the tetrahydric phenol had crystallised, a small quantity of another colourless, crystalline compound was isolated. This substance melts at 58O, and is sparingly soluble in water, but readily so in solutions of alkalis. There was, however, too little in our hands for identification. Not much tarry matter was formed, and practically all the butylphenol was oxidised. We expected to get a dihydric phenol (3: 4-di- hydroxybutylbenzene) as th-e chief product, but probably the fact that the mixture was heated for some time accounk for the formation of the more highly oxidised compound. A repetition of the experiment at a lower temperature may yield the dihydric phenol. Having obtained these results with phenols of the formula Cl0H,,*OH, it appeared of interest to investigate the behaviour towards perhydrol of some of the lower members of the series, and we selected as examples phenol and 0-, n2-, and p-cresols. Pre- liminary experiments showed that these compounds are more Published on 01 January 1910. Downloaded by University of Illinois at Chicago 03/02/2015 08:14:15. susceptible to the action of the oxidising agent than thymol and the other higher phenols examined, and that in order to prevent the formation of considerable quantities of tarry matters it was necessary to avoid using excess of perhydrol, to dilute the mixture with a larger proportion of acetic acid, and usually to carry out the oxidation at the ordinary temperature. Oxidation of Phenol with Perhydrol.-The phenol was mixed with perhydrol in such quantity that about 1 mol. of hydrogen peroxide was present for each mol. of phenol, and about twice the quantity of acetic acid necessary to keep the phenol in solution was added. After keeping for several days at the ordinary temperature, a crop of crystals had separated from the solution. The solid was collected, purified, and proved to consist of quinol,. by. determination of its melting point, 169O, and by its easy conversion into p-benzoquinone by oxidation with f emit chloride in aqueoua View Article Online

MONOHYDHTC PHENOLS WITH HYDROGEN PEKOXIDE. 1667

bolution. The liquid from which the crystals of quinol had been removed was distilled with steam, when a little 9-benzoquinone passed over and was collected. The residual liquid gave a precipitate when mixed with lead acetate. The first portion of the precipitate, which wits very impure, was rejected; the rest was collected and decomposed with dilute sulphuric acid. The filtrate from the lead sulphate was agitated with ether, and from the ethereal solution a solid which gave all the reactions of catechol was obtained. A further quantity of quinol was obtained from the liquid from which the lead salt of catechol had been separated, but no resorcinol could be detected. Thus, with the strong solution of hydrogen peroxide, the oxidation products from phenol were the same as those obtained by Martinon (loc. cit.) by the use of a dilute solution : OH OH OH 0

Oxidation of o-Cresol with Pel-hydrol.-The conditions of the experiment were the same as in the case of phenol, except that as the oxidation proceeded much more slowly at the ordinary temperature, the liquid was heated to 60° for two days, with the result that a considerable proportion of tarry matter was formed. The liquid was then distilled in a current of steam, and, along with some unchanged o-cresol, there passed over a yellow, crystalline compound, which was identified as toluquinone. The residual liquid was neutralised with sodium carbonate and agitated with ether, and from the ethereal solution, after washing with water and Published on 01 January 1910. Downloaded by University of Illinois at Chicago 03/02/2015 08:14:15. removal of the ether, a dark-coloured, oily residue was obtained. This residue was dissolved in water, and the tarry impurities were precipitated by addition of lead acetate; the filtrate was then found to contain toluquinol. No other oxidation products could be detected with certainty, although it is not improbable that the lead precipitate contained a little of such : Me iUe Ale

Oxidation of m-Cresol UitJt, Perhydrol.-The oxidation was carried out precisely as in the case of phenol. After being kept for a sufficient time, the liquid wm distilled in a current of steam, and the distillate was found to contain toluquinone, together with some unchanged m-cresol. The residual liquid was filtered in order View Article Online

1668 OXlDATlON OF MOKOHYDRIC PRENOLS.

to remove some tarry matter which was present, lead acetate was added to the filtrate, and the lead salt, which was precipitated, was collected. The filtrate was agitated with ether, and toluquinol was obtained on concentration of the ethereal extract. The lead salt was decomposed with dilute sulphuric acid, and the filtrate from the lead sulphate yielded to ether a substance with the reactions of orcinol : Me Me Me

Oxidation of p-Cresol with. Yerhydro2.-Preliminary experiments showed that p-cresol was not oxidised by perhydrol nearly so easily as 0- or n2-cresol, and consequently the mixture of p-cresol, perhydrol, and acetic acid was heated at about 60° for three days. The greater part of the acetic acid was then neutralised with sodium carbonate, and the oily liquid which was thrown out of solution was separated. The aqueous liquid gave no precipitate with lead acetate, which indicated the absence of isoorcinol. It was agitated with ether, and after the ethereal solution had been washed, the ether was removed by distillation, and an oily residue was left. This was mixed with the oily substance which had already been obtained, and the mixture was distilled. A large portion of the distillate proved to be unchanged p-cresol, but the fraction, which boiled at 240--255O, yielded on redistillation a syrupy liquid, which gave the characteristic reactions of homocatechol (3 : 4-dihydroxytoluene)-reduction of Fehling’s . solution and of ammoniacal silver nitrate in the cold, and with ferric chloride a green coloration which turned brown after some time. Published on 01 January 1910. Downloaded by University of Illinois at Chicago 03/02/2015 08:14:15. Homoca.techo1 was the only oxidation product detected : AI-0 Me /\ /\ ii --+ I \/ \/ OH OH Attempted Condensation of Resorcinol and of Quinol with Diethyl Ether.-In view of the fact that diethylphenol was readily obtained by condensing phenol with ether with the aid of anhydrous aluminium chloride, we thought it desirable to attempt to prepare corresponding dihydric phenols by a similar direct method. Accordingly, a mixture of resorcinol with ether was treated with aluminium chloride in the manner described by Jannasch and Rathjen (Zoc. cit.). Only a slight reaction appeared to take place even when the mixture was heated, and when the product. was View Article Online

SOLUBI1,ITY AKD THE PHYSICAL STATE OF THE SOLVENT, ETC. 1669

treated with water and worked up in the usual w'ay, practically nothing but unchanged resorcinol was obtained. An attempt to condense quinol with ether wits equally unsuccessful, and it is evident that these dihydric phenols do not undergo condensation with ether under the same conditions as lead ta the formation of diethylphenol. Condensation of Phenol uiit?~Methyl Proplll Et?her.--In order to ascertain whether the reaction between phenol and diethyl ether could be extended to other ethers, we prepared some methyl propyl ether, and condensed it with phenol in the following manner. Thirty grams of phenol were dissolved in an equal weight of pure ether, the solution was cooled, and 120 grams of anhydrous aluminium chloride were slowly added in small portions. The mixture was then heated at 140° until no more hydrogen chloride was evolved, and, after cooling, the mass was decomposed with water and the oily product extracted with ether. The ethereal solution was washed and dried, the ether removed, and the residue distilled. A little unchanged phenol passed over first, but the bulk of the product distilled at 130-140°. On redistillation of this fraction, an oily liquid, boiling at about 135O, was obtained. It is sparingly soluble in water, but easily so in alcohol or ether and in solutions of alkali hydroxides, and in aqueous solution it gives a dark green coloration with ferric chloride. Probably this compound is a methyZpropyZp?henoZ, C,H,MePr*OH. We propose to study the condensation of monohydric phenols with ethers more fully.

We take this opportunity of expressing our thanks to the Research Fund Committee of the Carnegie Trust for a grant which defrayed the expenses of this investigation. Published on 01 January 1910. Downloaded by University of Illinois at Chicago 03/02/2015 08:14:15. CHEMISTET DEPARTMENT, THE G LASGOW AND WEST OF SCOTLANDTECHXICAL COLLECE.