PREPARATION OF M-M -DIHYDROXY DIPHENYL ETHER HY CARL WILLIAM KUEHNE r rHESIS FOR TH K D E G R E E O E B A C II ELOR OF SCIENG E IN CHEMISTRY COLLEGE OF LIBERAL ARTS AND SCIENCES UNIVERSITY OF ILLINOIS 1922 VU5 UNIVERSITY OF ILLINOIS ___Max x __25 i 9 2 . 2 __ THIS IS TO CERTIFY THAT THE THESIS PREPARED UNDER MY SUPERVISION BY C_ar_l William _Kuehne_ ENTITLED i on. _9 H ?_y T&A Pi} ejiyi. _ ©t he r_ _ IS APPROVED BY ME AS FULFILLING THIS PART OF THE REQUIREMENTS FOR THE DEGREE OF c i_®.P_Q.§_ AH _Chemi f? t.rZ Instructor in Charge Approved \£ j _._ HEAD OF DEPARTMENT OF Ajt J Digitized by the Internet Archive in 2015 https://archive.org/details/preparationofmmdOOkueh ACKNOWLEDGMENT . The author wishes to express his deepest t appreciation to Dr. Carl S. Marvel for the helpful suggestions and optomistic encouragement which were given during the course of this research. TABLE OF CONTENTS Introduction 4. Theoretical and Historical 5. Experimental 8. Preparation of m-m-dimethoxy-diphenyl ether 8. Preparation of p -n i t r o -b r omo -b en z en e 9. it n pot as sium-p -nitre -phenol at e 9. it tf p-p’-dinitro -diphenyl ether 10. tt tt p-p'-di amino -diphenyl ether 11. Acetylation of p-p’-di amino -diphenyl ether 11. Nitration of p- -p’-diacet amino -diphenyl ether 12. Preparation of m-nitro-benzene-diazonium sulfate 15. tt tt m-nitro -phenol 15. tt tf pot assium-m-nitro -phenol ate 16 . tt tl m -n i t ro -b r omo -b en z en e 17. tt tt m-m’-dinitro-diphenyl ether 17. Summary 19. Bibliography 20. 4 . INTRODUCTION. Resorcinol ether, or m-m-dihydroxy- diphenyl ether, is recorded in the literature as "being prepared by treating resorcinol with HC 1 , or by simply heating. In this way, a red amorphous powder, with a melting point range of about 200°, is obtained. As the condensation products of both pyro catechol and hydroquinone give white compounds with definite melting points, it is to be expected that resorcinol ether should be a product of the same type. Meyer and Marx 1 have practically shown that the red powder is a mixture of substances. They isolated a product of the formula C14H12O3 from the reaction mixture obtained by heating resorcinol; or better, by heating it with zinc chloride. It is therefore the purpose of this thesis to attempt to prepare resorcinol ether by synthetic methods with a view of refuting the statement in the literature that the red amorphous substance is a simple substance. With this in mind, the work on the analysis of the condensation product of resorcinol may proceed. 5 . THEORETICAL AND HISTORICAL. In the preparation of m-m'-dihydroxy-diphenyl ether, it was deemed advisable to make a diphenvl-ether derivative early in the synthesis, and then to react it in such a manner that the groups on the rings would be changed or replaced in a definite manner. The one that suggested itself first was to prepare the ether by reacting resorcinol mono-methvl ether with metallic aluminium. £ cu/r £ p According to the literature , the main reaction should be the formation of m-m-dimethoxy-dipheny 1 ether. By fractionating from ten to twenty times, a pure product should be obtained. Having the m-m’-dira ethoxy -diphenyl ether, it could be treated with hydriodic acid, when it would form m-m-dihvdroxy-diphenyl ether and methyl iodide . Another method would be to go through a long series of reactions starting with p-p’-dinitro-diphenyl ether. The first reference^ to this particular compound in the literature advised heating a mixture of p-nitro-chloro -benzene, p-nitro-phenol , and potassium hydroxide on a bath at 225°. Later experiments^ showed that the reaction went less than 1%; but by using metallic copper, and p-nitro-bromo -benzene in place of p-nitro-chloro-benzene, a yield of over 90% was obtained. Another experiment'' showed that even if copper were used to catalyze the reaction, a yield of only 25% could be obtained if p-nitro-chloro-benzene was used. The next step is to reduce the p-p’-dinitro -diphenyl ether to p-p’-di amino -diphenyl ether. It was recommended^ to Use zinc and hydrochloric acid. However, it was thought that iron filings and a trace of ferrous chloride would be active enough to reduce this particular compound. The amine groups of the p-p-dinitro-diphenyl ether must be protected with acetyl groups during the subsequent nitration. Theoretically, the acetylation is very simple. Dissolving the p-p’-di amino -diphenyl ether in glacial acetic acid and warming on the steam-cone should be sufficient to acetylate completely. In the nitration, it was desired to make a nitro group go onto each ring in a position meta to the ether grouping. This is best accomplished in an acetic acid solution, without warming. However, concentrated sulfuric acid is generally accepted as an excellent nitrating medium, and might prove more successful than the glacial acetic acid, even though sulfuric acid tends to make the nitro group go in the ortho position. The plans after having nitrated successfully, were to split off the amino groups by diazotizing, and then replacing the diazo group with hydrogen, in an anhydrous solution of a higher al cohol . The m-m’-dinitro -diphenyl ether wa3 then to be reduced, again using iron filings and a few drops of hydrochloric acid. The diazonium derivative would then be prepared by means of nitrous acid in a cold solution. The solution would be boiled in a very large volume of water to decompose the diazonium group w r ith a liberation of nitrogen with the formation of a hydroxy group. A large volume of water is necessary in this reaction ■ ' ■ 1 r - 7 . in order tc prevent as much as possible the formation of tars. A third method of synthesis begins with m-nitro-bromo -benzene and m-nitro-phenol . These particular compounds were thought to be difficult to prepare, but with good m-nitraniline, the reaction should go in very good yields. In each of the preparations, m-nitro-benzene-diazonium sulfate is prepared first. To make the former, this is warmed with cuprous bromide; and for the latter, it is boiled with a very large volume of water. As the bromine atom met a to a nitro group is supposedly very unreactive, difficulty may be encountered in forming the ether. However, if even a very small yield would be obtained, it would be encouraging, since when the m-m’-dinitro-diphenyl ether is at hand, all that need be done to prepare the m-m’-dihydroxy- diphenyl ether would be to reduce, diazotize, and decompose the diazonium group by boiling. 8 . EXPERIMENTAL. Preparation of ra-m’-dimetho xy -diphenyl ether . Thirty grams of resorcinol mono-methyl ether and six grams of aluminium foil were put in a small flask and connected to a reflux condensor. A crystal of iodine was then dropped through the condensor and a flame put under the flask. In about fifteen minutes signs of reaction were noticed, and the burner was removed. The reaction gained in velocity until it became so vigorous that wet cloths had to be applied to prevent the mixture from coming out of the top of the condensor. When the reaction had subsided, the mixture was destructively distilled in order to decompose the alminium triphenolatederivative of resorcinol mono-methyl ether. It began to distill over at about 100°, and when it had reached £90° no more could be made to distill. A blue-black glistening char was all that was left in the distilling flask. It was then attempted to distill and fractionate the distillate from decomposition. Several cuts were made, but most of it seemed to boil around 243°, the boiling point of resorcinol mono-methyl ether. If it had been known where m-m'-dimethoxy- diphenyl ether boiled, very likely some of it could have been isolated by cutting the fractions at the correct points; but as it was, nothing was known about this particular compound. 9 . Preparation of p-nitro-bromo -benzene . In a 500 cc. flask was placed 60 cc. nitric acid(sp.gr. 1.42 ) and to this was carefully added 60 cc. sulfuric acid (sp.gr . 1.84 ) . When thoroughly cooled to room temperature, 40cc. of bromo-benzene was added in very small portions, shaking continually. The solution had a tendency to get quite hot, so it was cooled by allowing tap- water to flow over the flask. Large clods of p-nitro-bromo -benzene precipitated. When the reaction had calmed, and showed no tendency to heat up, it was placed on a steam-cone for an hour, and then poured into 200 cc. w r ater. The precipitate was filtered off, and washed well with water to remove the acids. The mixed p- and o-nitro- bromo-benzene was dissolved in hot alcohol, and then cooled. The p-nitro-bromo-benzene crystallizes out when the solution is cooled, while the o -nit ro -bromo-benzene, which is fairly soluble in alcohol, remains in solution. The yield was 50 grams, or 76 %, Preparation of potassium p-nitro -phenol ate . Twenty grams of K0H was dissolved in 100 cc. water, and added, with stirring, to 70 grams of p-nitro -phenol in 200 cc. water. The suspension was boiled until it dissolved. It was then cooled. The thick precipitate which formed was sucked free from the liquid by using a Buchner funnel. The crystals were then washed with several small portions of alcohol. It is of a deep yellow color. 10 . Preparation of p-p-dlnltro -diphenyl ether. One hundred and fifty grams of p-nitro-bromo -benzene was thoroughly mixed with 112 grams of potassium p-nitro -phenol ate in a large flask, and about one-half gram of pulverized copper added to catalyse the reaction. The mixture was heated on the steam-bath for several hours, and then on an oil bath for several days at a temperature of about 175° and not exceeding 190°. At the end of this time the mixture was leached with water to wash out the KBr and unreacted potassium p-nitro -phenol ate. The excess of p-nitro-bromo-benzene was removed by prolonged steam distillation. The condenser was omitted and the steam run under water, as the product solidified, clogging up the tube. The brown mass remaining in the flask was extracted with benzene. The first extractions needed no recrystallization, but the later ones had to be re- crystallized from hot alcohol. Some of the lower melting portions (85°-93°) could not be purified. The yield of product melting at 138° was 35#. On some of the rune no p-p-dinitro -diphenyl ether could be isolated, due perhaps to the excessive heating above 200°. A mixture melting between 84° and 95° was the only product obtained. P-nitro-chloro-benzene was used in several of the runs in place of the p-nitro-bromo-benzene, but practically all of the original substances was recovered ■ uncombined. Care must be t en to heat the mixture rather slowly. because if heated too rapidly, the reaction is very liable to become quite violent. 11 . Preparation of p-p-di amino -diphenyl ether . Fifty grams of p-pt-dinitro -diphenyl ether was mixed with a large excess (about 150 grams) of iron filings. Enough water was added to form a thick paste, and this was followed by a few drops of concentrated HC1. During most of the time of the reaction, which was strongly exothermic, the mixture was vigorously stirred. In a couple of hours, when the filings had cooled to some extent, it was heated on the steam-cone to complete the reduction. The rapid evap- oration necessitated an occasional addition of water. The mixture, when it was dried on the steam-bath to facilitate subsequent extractions, had a tendency to solidify in a hard cake. This was overcome to a large extent by stirring frequently. When completely dry and powdery, the mixture was extracted with benzene to remove the unreduced p-p’-dinitro-diphenyl ether. The residue was extracted with hot acetone until the extraction liquors from the iron filings were almost colorless. The p-p*-di amino -diphenyl ether was obtained by just evaporating off the acetone. By this method a very pure product was obtained, the melting point range being only two degrees. The yield on the several runs averaged 80^ of the theoretical . Acetylation of p -p -di amino -qipheny 1 ether . Ten grams of p-pf-di amino -diphenyl ether was dissolved in 100 grams of acetic anhydride (tech), and heated on a steam-bath for three days. At the end of this time, the solution was poured into ?00 cc. water. It did not mix, but formed an oil which was decom- posed on boiling. As the oil disappeared, a dark pink precipitate formed. After boiling for several hours, it was filtered. . Ill . - . - . - - « - . 12 . The melting point remained constant after crystallizing several times from ethyl alcohol, acet P-p’-d^amino -diphenyl ether is a light pink compound melting at 126'-] 27° ( corr ) . Ethyl alcohol and acetone dissolve it very readily, while it is almost insoluble in benzene and ether. The yield was 85$ of the theoretical. Analysis: 0.2000 gram sample; 5.9 cc. of 0.250 N.HC1; $ N calculated from the molecular formula-9 .8$; $ N found-10.1$. 0.2000 gram sample; 18.0 cc. N at 28°C and 746.7 mm. $ N calculated from the molecular formula-9 .8$; $N found-9.7$. As the calculated f of N for the mono-acetyl derivative is 11.5$, these analyses show conclusively that the compound obtained was p-p-di acet amino -diphenyl ether. N itration of p-p-di acet amino -diphenyl ether . It was first attempted to nitrate the p-p’-diacet amino -diphenyl ether with the theoretical quantity of fuming nitric acid. Six grams of the ether was dissolved in 15 cc. glacial acetic acid. To this was slowly added a mixture of 2 cc. fuming nitric acid, 5 cc. glacial acetic acid, and .1 gram urea, the latter being for the purpose of preventing oxidation. When one and one-half cc. of the nitric acid solution had been added, the solution of the ehher changed from a deep red to a light yellow. The change in color had taken place slowly. Then suddenly, when about 2 cc. was added, the solution turned dark red again, and remained so during the addition of the rest of the nitric acid. The flask was allowed to stand in a cool place over night. In the morning, while shaking and examining the contents of the flask, the mixture suddenly 13 solidified to a mass of bright yellow crystals; not a trace of the red coloration remained. After letting stand a day longer to be assured of complete nitration, water was added, and the acetic acid sucked from the crystals. They were then washed free from acid with water. The nitration product was partly soluble in alcohol. The filtrate from the first washings was reddish-brown; but after washing several times, the alcohol came through almost colorless. The compound was dried, and found to melt 197 and 199°: it had previously at various stages in the purification melted at points ranging from 160° to 206°. Six grams of product was obtained. Analyses: 0.3000 gram sample; 369.0 cc. C0g collected at 23° and 740.0 mm; $ C calculated for C^qHj(. 0^N, 7 -58 . 3$; $ C found-58.0^. 0.2000 gram sample; 23.7 cc. N collected at 742.6 mm. and 28°; $ N calculated for C^H^OgN^- 12 . 8 ^; «f ; ^ found-12.7$. As the mono-nit ro derivative of p-p-diacet amino -diphenyl ether was conclusively obtained, an effort was made to put another nitro- group on by using a 100^ excess of fuming nitric acid, but the mono-derivative was obtained in this case also. Then heating was tried. Two grams of p-p-diacet amino -mono - nitro-diphenyl ether was dissolved in glacial acetic acid, and the theoretical amount of fuming nitric acid added. It was heated on the steam cone for one day, and then cooled. As no precipitate formed, it was poured into water. Everything was completely soluble to a yellowish solution, except for a small amount of very fine black powder. Not enough of it was collected to analyze, but it was assumed to be carbon. On making the solution alkaline, it became red, but no precipitate formed. Apparently, the ether 14 broke down into a phenol. Concentrated sulfuric acid was then tried in place of the acetic acid. In the cold, p-p’-diacetamino-mono-nitro-diphenyl ether was isolated; and on warming, it, too, decomposed, giving compounds soluble in both dilute acids and alkalies. As no p-p’-di acet amino -ra-m-dinitro -diphenyl ether was obtained by any of these methods, work on this series of preparations was suspended. - 15 . Preparation of m-nitro -benzene-diazonium sulfate . Fifty grams of m-nitraniline was suspended in 200 cc. water, and 100 co. cone, sulfuric acid added with stirring. In some cases it may be necessary to warm on the steam-cone to completely dissolve it. The hot solution is poured with stirring into a large beaker containing a liter of water and cracked ice. A fine pink precipitate separates. When the temperature reached 0 C , 26 grams of sodium nitrite disolved in 150 cc. water was added rapidly with stirring. The temperature should be kept as low as possible, preferably below 5°. In a few minutes, the solution was filtered. Preparation of m-nitro -phenol . For each 25 grams of m-nitraniline used in preparing the m-nitro -diazonium sulfate, 300 cc. cone, sulfuric acid diluted to two liters was added. The total volume was about eight liters. The solution was heated in a large copper can. At about 85°, the nitrogen began to come off with vigorous bubbling. When it began to boil, it became quite turbid, but after boiling for thirty minutes, it became clear, with some tar floating on the surface. It was filtered hot through a Buchner funnel prepared by placing one inch sand on top of the funnel to prevent the tar from going through. Before using, the sand should be treated with 1:1 sulfuric acid. When cold, the filtered solution was thoroughly extracted with ether. When the acid solution no longer becomes red when made alkaline, the m-nitro -phenol lias been removed. 16 . After distilling off the ether as completely as possible, the remaining oil should crystallize. In most of the cases no difficulty was encountered; however, if even a small amount of water is present, the crystallization will be hindered, or even prevented. The crystals were washed with benzene until they were of a light cream color. The benzene used in washing was added to the mother liquors and distilled off. It was found that a much better product could be obtained by dissolving the m-n it ro -phenol in hot 1:1 HC1. After cooling to about 40° the solution was decanted, or filtered if necessary, and allowed to cool slowly, finally placing the beaker in ice water. Beautiful large white crystals of very pure m-nitro -phenol formed. A yield of 70^ was obtained. Preparation of potassium m-nit ro -phenol at e . Tw r enty grains of KOK was dissolved in 100 cc. water, and added slowly with stirring to a suspension of 70 grams of m-nitro -phenol in 200 cc. water. After boiling for a short time, the phenol dissolved. The mixture was allowed to cool. When it became a solid thick mass, the liquid was sucked off in a Euchner funnel. After washing several times with small portions of alcohol, the crystals lost their deep red color, and became a reddish orange. A considerable amount of potassium m-nitro -phenol ate may be recovered from the liquors sucked through the funnel by evaporating to a rather small volume, and allowing to cool in the same manner as the original solution. - - - 17 Preparation of m-nitro-bromo -benzene . In a two liter flask was put 45 grains of crystallized copper sulfate, 150 grams of KBr, 150 cc. water, P0 grans of copper turnings 7 and 9 cc. of concentrated sulfuric acid . The flask was connected to a reflux condensor, and heated on a flame until the solution \vas colorless. If sulfur dioxide is passed in, the reduction takes place much more rapidly. However, the excess must be boiled out. In the meantime a solution of m-nitro-benzene-diazonium sulfate was prepared, using 50 grans of m-nit rani line . Both of the solutions should be ready for use at the same time The m-nitro-benzene-diazonium sulfate was added slowly to the cuprous bromide solution, which was removed from the free flame and placed on the steam bath to facilitate the vigorous shaking which is necessary. The solutions should be kept as hot as possible and be mixed rapidly to insure a good yield. When all had been added, the m-nitro-bromo-benzene was distilled over with st9am. It was filtered from the water and dried. The product was quite pure, and needed no further furif ication. The yield was 75fo. Preparation of m-m-dinitro -diphenyl ether . Fifty-six grams of pot as sium-m-nitro -phenol ate was thoroughly mixed with a slight excess, 75 grams, of m-nitro-bromo-benzene, and about one-half gram of powdered copper. The flask was connected to a reflux condensor, and left on the steam bath for several days. The mixture became semi-solid. Then it was put in an oil bath, and heated up very slowly until it reached 150°, where it was held for about five hours. After this time, indication of charring were 18 noticed by the black deposits around the edges. The mixture was cooled, water added, mixed well, and decanted. The potassium-m-nitro- phenolate which crystallized out from the wash water was recovered. After removing the excess of m-nitro-bromo -benzene by steam- distillation, the residue, which was in the form of dark brown pellets, was ground in a mortar, leached with water, and again steam- distilled, for the purpose of removing the last traces of potassium- m-nitro -phenol ate and KBr, and m-nitro-bromo -benzene respectively. After this treatment, the product was dissolved in benzene. On evaporating the solution a product solidified out which had a melting point range from 105°-120 c . Recrystallization from hot alcoho] was tried, but the melting point did not change more than a few degrees, the main range being quite constant. Acetone and ether were tried in both the extraction and recrystallization, but with the same result. 19 SUMMARY . None of the methods tried for preparing m-m’-dihydroxy-diphenyl - ether succeeded. The one in which resorcinol mono-methyl ether was used may have remote possibilities. The second synthesis, that in which the reaction are carried on from p-p'-dinitro-diphenyl ether, was entirely unsuccessful, due to the inability to prepare m-rc-dinitro-p-p-diacet amino -diphenyl ether, getting instead only mono-nitro-p-p-diacetamino-diphenyl ether. The method starting with m-m-dinitro -diphenyl ether seems to be promising, if work on this problem were to be continued, the author would suggest that synthesis which starts with m-nitro-bromo-benzene and potassium- m-nitro -phenol ate, because of the few steps in the synthesis, and the smoothness with which they should go, with the exception of the coupling of the first compounds to form the ether. _ 20 BIBLIOGRAPHY. 1 . Ber . 40 1450-53 (1907 ) 2. Ber . 12 1925 (1879 ); 14 3. Ber. 29_ 1448 4. Ber. 38 2211 5. Ann. 550 83-107 (1906 ) 6 . Ber. 29 1449 7. Noyes Org.Chem. P.202 (1881 )