I I \ \ / THE PREPARATION OP" PARA-PHENOXY-PHENYL-ARSONIC ACID BY SEYMOUR HOUGHTON COOK. THESIS FOR THE DEGREE OF BACHELOR OF SCIENCE in CHEMICAL ENGINEERING COLLEGE OF LIBERAL ARTS AND SCIENCES UNIVERSITY OF ILLINOIS 1921 o/n UNIVERSITY OF ILLINOIS Uf CO i92_i. THIS IS TO CERTIFY THAT THE THESIS PREPARED UNDER MY SUPERVISION BY .SBmQUE._lLQUilHTmi_ilQM. ENTITLED THP PREP ARAT ION OR PARA-PH?,N QAY -PIia^YL ~ARAQl.LlCL IS APPROVED BY ME AS FULFILLING THIS PART OF THE REQUIREMENTS FOR THE DEGREE OF 3ax^ J siox_a£_^cJLeiia£.-lii_XItieiniiiaX- J HEAD OF DEPARTMENT OF CI^ISTRY 49 Digitized by the Internet Archive in 2015 https://archive.org/details/preparationofparOOcook FQ-iSWORD . It is with great pleasure and sincere respect that the writer of this paper takes this opportunity of expressing his full appreciation of the cooperat- ion and guidance afforded him "by Dr. Doger Adams in the suggestion and prosecution of this investigation. . ITABES OF CQirTlulI^o , Sub.icc t . Pace . Introduction . 1 Historical 2 Experimental Sodium Phenolate 5 ~ -nitro-chlorbenzene 6 Mono-nitro-diphenyl ether from sodium phenol- ate and p-nitro-chlorbenzene 8 Mono-nitro-diphenyl ether from potassium phen olate and p-nitro-brombenzene '10 Mono -amino -diphenyl ether — 12 Par a-phenoxy-phenyl-ar sonic acid 13 * Summary ■ ■ 14 References 16 Mote: -umbers within brackets, i.e. lid), refer to references on page sixteen. mono -nitro- diphenyl ethers and their derivatives ( 14 ) , and it was thought best to try out their method of preparation in the product- ion of the mono-nitro derivative to he used in this work, Some of the results obtained by the writer were not at all in agreement with those obtained by the investigators referred to above. It is with a view to throwing further light upon the phenomena observed in the preparation of this compound, that the experimental work carried out by the writer will be reviewed in detail. Historical . The method employed in the work undertaken in this problem, for introducing the arsenic acid group into the ben- zene nucleus is not a new one, but one that has found extensive ap- plication in the preparation of similar organic arsenical compounds. It involves the replacement of the diazonium grouping with the ar- senic acid group by means of running the water solution of the diaz- oniun salt into a sodium carbonate solution of arsenious oxide at a temperature of from 0° G . to 15°C. in the presence of copper sulfate which acts as a catalyst. Nitrogen is evolved and sodium chloride is formed at the same time that the arsenic acid grouping enters the ring nucleus. Some of the earlier methods employed for the re- placement of the diazo grouping have differed in their detail from this general method, but where ever a catalyst has been employed, it has been found that copper, silver, nickel, or cobalt, as well as their salts facilitate the removal of the diazo nitrogen at low temp- eratures, and obviate the formation of byproducts (l6 ) • In the preparation of 3*. 5-dichlorophenyl-arsenic a -o- acid, 3: 5-aichlor-p-arsanilic acid was diazotized by Morgan accord- ing to Witt's process(l). The clear cold nitric acid solution of the diazotized compound was mixed with alcohol and a srn, 11 amount of finely divided copper. Effervescence set in at the temperature of ice, and was completed by gentle heating. The copper was complete- ly dissolved, and the solution was again cooled. The 3:5-dichlor- phenyl-arsenic acid separated out in crystals. Many other aromatic arsenic als have been x>re- pared in a similar manner. Among the most important of these are those which are briefly mentioned below: T-phenylene-diarsenic-acid has been perpared(s) by the diazotization of sodium-p-arsanilate , and warming the diazo- tized solution with sodium arsenite without a catalyst. P-phen-phenyl-arsenic acid v/as prepared by Bit- termann(io), by the use of Bart's reaction for replacing the diazo- niurn group with the arsenic acid group. Phenyl-acetic-p-arsonic acid was prepared- by Gr. A. Hobertson and J. Stieglitz from p-amino-phen-acetic acid(ll). Phenol -p-arsenic acid has been prepared by Mor- gan from p-amino-phenol by Part's reaction without a catalyst, but with a slight application of heat (2). 2 :4-dinitro-arsenic~ acid has been prepared by Morgan from 2:4-dinitro-aniline (2 ) . The best yields were obtained with an excess of acid in place of with a neutral or alkaline sol- ution of sodium arsenite. 3- nitro-4-hydroxy-phenyl-arsenic acid has been prepared by Morgan from o-nitro-p- .mino-phenol (2 ) . 4- nitro-2-hydroxy-phenyl-arsenic acid was also -4- prepared by Morgan iro.:. 4-nitro-2-a o -phenol by Bart’s reaction with alkaline sodium arsenitefs). 3- amino-phenol-6-arsenic acid was prepared by Morgan from 3-nitro 6- amino -phenol and subsequent reduc tion( 2 ) . Jacobs, Heidelberger , and Molf have prepared sev- eral nitro and amino aryl arsenic acidsfd). Morgan has prepared p-c v loro-phenyl-arsenic acid ; from p-chloraniline f 2 ) . P-tolyl-arsenie acid has been prepared by Bart’s reaction when a solution of p-toluer.e-diasonium-chloride is treated with a neutral aqueous solution of sodium arsenitc, and the mixture is gently warmed to evolve the nitrogen(2J. The following arsonic acid derivatives of anth- raquinone have been prepared by I. Benda(7). ^nthraquinone-2-arsonic a-cid. 4- amino-anthraquinone-l-arsonic acid from 1:4- didmino-anthraquinone . 4 : 8-dihydroxy-anthraquinone-l : 5-diarsonic acid, from 1 : 5 -diamino- an thraquinone . In addition to the above mentioned preparations, A. Schmidt, Heysler, and Modebeul have done considerable work on the diazo synthesis of aromatic arsonic acids, and have shown their theoretical importance in relation to similar reactions (9 )» a. Mouneyart also has done considerable work up- on aromatic arsonic acids obtained by the reaction of aromatic di- azo com n is upon acid, neutral, and alkaline aqueous and alcoholic solutions of arsenious ac.id in the presence of copper salts, and an appropriate reducing agent. The reducing agents used most generally for an acid solution are HgPOg, Na^POg^nd KCi t or CuOH; for neut- ral solutions ^ a 2^2^4» or Sodium-formaldehydesulfoxalate ; Tor al- kaline solutions HCIIO Hypo sulfite, or formal ' 1' oxalate, or Ha- AsO’- in excessflS). Hicoerir.iciatal . The final product of this investigation was pre- pared through the following series of reactions; ^ < 7 ^ 0 ^ — > + /**c/ o/K -h * <0 c Y- jnf&A . <^>- v~<^>'/YBA / +-^<*3 '4*0? — > ^ . 0-^0 *2sVbroduct became a very stiff paste. It was then removed and ground to a powder i r, and placed in a stoppered flask to keep. By this method of procedure very little, if any, e takes place and a creamy-white product results. Totassium phenolate was prepared in the same manner. The Preparation of B-nitro-cklor-benzene, P-nitro-chlor-benzene was prepared by nitrating 94 grams of chlorbenzene with 100 cc . of fuming nitric acih - The mixture was kept at a temperature of not over 40°C. when all the chlorbenzene had been added slowly to the nitric acid through a drop- ping funnel, while continuously stirring the mixture, it was pourred into a large volume of cold water. There was formed a heavy oily substance, th::t settled to the bottom of the vessel, and partially crystallized, forming a semisolid mass. The crystals of p-nitro- chlorbenzeme were filtered off by suction and dried. The total yield of the para compound was 45 grams. A second run was made for the preparation of this compound, closer attention being paid to the amounts of perw and -7- ortlio compounds produced. 108 gms, chlorbenzene. 150 cc . fuming nitric acid. G5 gms. p-nitro-chlorbenzene. 192 gms. o-nitro-chlorbenzene. 257 gms. 265 gms. Yield in percent of theory 97.# In the second run no crystallization took place upon pourring the nitrated mixture into cold water, so the mixture was again separated hy means of a separatory funnel, and washed with a dilute solution of sodium hydroxide. The oily material was then run into water from the separatory funnel and allowed to stand for some time. Crystals of the p-compound formed and were filtered from the heavy oily o-compound. The o-compound was then placed in a flash and cooled to 0°C. with an ice hath. A few crystals, formed hy freezing a small amount of the oily liquid in a test tube, were introduced into the liquid in the flash. A rapid growth of cry- stals ensued. The temperature of the freezing oily liquid was 14.89 A third run was made in an attempt to obtain larger yields of the p-compound. A glass stirrer, turned hy a smell electric motor was employed and the temperature was hept constant hy placing the nitrating flash in a large volume of running cold water, ho better results were obtained, theyield of the p-compound being only 2 Ok The p-nitro-chiorbenzene , prepared as above, was used in the early part of the worh done in the preparation of mono- nitro- diphenyl ether, but later on, the commercially prepared com- pound was available, as well as p-nitro-brombensene , and these com- mercially prepared compounds were, therefore, used in the later worh. Ingredients : Yield*. Total Yield: Theoretical : - 8 - T'henolate and _ itro-Ghlorbenzene '-'he -'-'c A : a i ' - L uio-Titro-fiohenwl Ather from Sodium 100 grams of sodium phenolate we re dissolved in 100 grams of phenol at 150°0. The resulting mixture was a "black looking fluid. Into this black fluid was introduced 50 grams of p-nitro-chlorbenzene. The mixture was then refluxed for 21 hours. A heavy black tary mass was evident in the bottom of the flask at the end of that time. The solution was then washed with dilute sod- ium hydroxide and the alkaline solution was then washed with ether, and the ether pourred off the top. Considerable difficulty was ex- perienced in making the separation of the two 1 yeas, because of the dark color of both. The ether extract was evaporated to dryness on the steam bath and a second ether extraction of the dark mass was made. The ether solution was then pourred into a large amount of petroleum ether. A heavy dark liquid settled to the bottom of the mixture in a small amount, about 20cc. This dark liquid was sep- arated out by means of a separatory funnel and the process of ether extraction and subsequent pouring into petroleum ether repeated sev- eral times. The liquid was finally evaporated to dryness, dissolved again in ether, and again evaporated to dryness on the steam bath. The remaining mass was still black, but there was evidence of the formation of crystals. This partially crystalline residue was again taken up in ether and repeatedly shaken with animal charcoal. The charcoal was filtered off and the resulting filtrate was again evap- orated to a small volume. The dark crystals that resulted were filt. ered off, and dried, and their melting point determined. They melt- ed at 47°C. Several runs were made on the preparation of this -9- comoound. J-I10 sodium phenolate and the p—nitro— chlorbenzene wore mixed together in equal proportions, both with and without phenol as a solvent. The temperature t6 which they were subjected was also varied from 10G°C. to 150°C. f and the le gt of time of the heating r/as also varied. The best results were obtained by heating the two in equal proportions upon the steam bath for 30 hours, extracting the product with ether, and crystallizing from alcohol. The highest field obtained by this method was 55$. The product from the first )rop of crystals melted at 58°C. to 59°C. That of the second crop melted at from 57.5°C. to 58.5°C.,and that of the third crop from 57°-. to 58. 3oC . The first crop of crystals was a pale yellow col- or, and the other two crops were slightly darker. In preparing the mono-nitro-diphenyl ether by the above mentioned method, the powdered sodium phenolate and p-nitro- chlorbensehe were tnoroughly mixed in a 500cc. round bottom flask to wnich an upright air cooled condenser tube was attached, and the mixture was nsateci on the steam bath. During the heating, a large amount of long needle-like crystals formed at the neck of the flask, ana in one lower end or the condenser tube. Before extracting the 1 eac cion pro ciuc c witn ether, some or these crystals were removed 110,1 khe u°p 0- cne flask, and their melting point was determined. It was found in three of the runs in which this method was used that the sublime crystals melted at from 82°C. to 85°C. in the first, 79 . 5°G . to 82°G. in the second, and from 82.5oC. to 83. °C, i n the third. T-nitro-chlorbenzene has a melting point of 85 °C. t so it was assumed that these sublimed crystals were nothing but crystals or the original p-nitro-chlorbenzene which had not reacted. This assumption was born out by the appearance of similar phenomena oc- S 1 - 10 - cur ring in work done later with p-nitro-brombenzene . The Preparation of Aono-Uitro-Uiohenvl Ather from Potassium Phenolate' 1 E-I-Atro-Arombonzenc ~ In their work upon mono-nitro diphenyl ethers, •Jones and Cook employed potassium phenolate and p-nitro-brombenzene fl4), and they claimed to have been able to obtain yields of 82/^ of the theory, and a pure white crystaline product. Using their me- thod of preparation, the writer heated 50 grams of each of these two compounds together in a 250 cc . round bottom flask for twenty hours on a steam bath. At the end of this time the needle like cry 3 tala which had formed at the top of the flask were removed, and were found to have a melting point of from 121°C. to 124°C, After the heating was continued for foir days, the. crystals that had form- ed were again examined, and these v/e re found to have a melting poinLt of from 106°G. to 118°C. It was assumed from these facts that the crystals first examined were nearly pure sublimed crystals of p- nitro-brombenzene which had not yet reacted. This was in accor- dance with the results expected from the previous work with p-nitro- chlorbenzene. The fact that after the additional heating, the cry- stals that were formed at the top of the flask were found to melt at a lower temperature may be explained by the very probable assumption that these latter crystals were contaminated with the lower melting mono-nitro-diphenyl ether which was the product of the reacting sub- stances. The nitro- diphenyl ether was extracted from the mass with ether and then crystallized from alcohol. The product melted at from 48 oC . to 52°C. . - 11 - A second run v. r as made in the sane manner as the first, except that the mixture was heated for only 18 hours on the steam hath and 2 hours in an oil hath at 150°C. The yield ob- tained was 47 grams from 50 grams of p-nitro-brombenzene. Therefore the yield was 88 . 6/0 of the theory. The product melted at from 56°C. to 57 oC. In all subsequent preparations of this compound according to this method the product obtained with one crystallization from alcohol was very light yellow, and had a melting point of between 56°C. and 60°C. The results of the work carried out in the p repara tion of the mono e-nitro- diphenyl ether with both p-chlor and b> Ur brombenzene have lead the writer to believe that the ssumption, made by Jones and Cook(l4), that the sublimed crystals appearing at the top of the flask containing the reacting substances were the -pure mono-nitro-diphenyl ether was erroneous, and that such crystals are nothing but some of the original substance employed which has sublimec and condensed upon the cooler portions of the flask without reacting with the potassium phenolate. The writer also believes that the true melting point of the pure mono-nitro-diphenyl ether is not 123.5 as was supposed by Jones and Cook, but that it is very close to 61°6. as it was found to be by Haeussermann and H. Teichmann(l7 ) . The writer also wishes to point out the fact that the theoretical percentage of nitrogen in mono-nitro-diphenyl ether is 6.5/3 and not 12.3/3 as was stated by Jones and Cook(l4), and that even if it were, the fact that their analysis of the sublimed crystals showed a nitrogen content of 12 . 21/0 would not show that the ; crystals were pure mono-nitro-diphenyl ether, for the molecular weight of p-nitro-brombenzene is very close to that of mono-nitro-di- - 12 - phenyl ether and its percentage content of nitrogen is also very close to that of the latter compound, being 6.8/*>. The Preparation of liono-^mino-^inhenvl -fther from Llono- hitro- fi phenyl ^ther . This compound was prepared according to the method of Jones and Cookfld). In working with 75 grams of the nitro compound considerable difficulty was experienced in the de tinning of the solution of the reduced mixture. *-s carried out, 250 cc. of al- cohol were used to dissolve 75 grams of crude mono -nitro -diphenyl ether on the water bath. 75 grams of tin were added and the evolut- ion of hydrogen was produced by the slow addition of 100 cc. of hy- drochloric acid through a dropping funnel. The mixture was refluxed for several hours on the steam bath. The solution became turbid, and water was added to decrease the turbidity. The alcohol was boiled off, and part of the water evaporated. A heavy light colored precipitate of the amino- compound formed. Some of this precipitate was removed and its melting point determined to be 92°C. to 94°C . A large volume of water was added to dissolve all the amino compound and the solution filtered. The large amount of filtrate was evap- orated to a small volume on the steam bath, and allowed to cool. Shining white crystals crystallized from the solution. These had a melting point of 95°C. In order to obviate the difficulty of com- pletely de tinning the large volume of solution, it was decided to make the reduction with iron and a small amount of hydrochloric acid. The reduced mixture was allowed to cool, and the amino compound cry- stallized out. The excess iron and the crystalline p>roduct v/ere , -13- filtered from the solution and sucked dry upon the suction filter. The amino compound was extracted with ether, and crystallized from alcohol. fhe product was slightly colored, aand gave a melting point of 87°C. lii c Production of I-fhenoxo -Ihew\fL--rsonlo -cid . In order to prepare this compound from p- amino- diphenyl ether use was made of Bart’s reaction for the replace- ment of the diazonium group by the arsenic acid grouping. fen grams of the amino compound was treated with 8.5 cc . of concentrated hyd- rochloric acid, and the hydrochloride formed dissolved in 400 cc . of water. 3.1 grams of HaNOo was dissolved in 25 cc . of water, and dropped with vigorous stirring into the ice cold solution of hydro- chloride. fhe temperature of the mixture was maintained at 5°C . throughout the addition. ^ solution of sodium carbonate was made up, containing 20 grams of the salt, and to this were added 12.8 grams of arsenious oxide. fhe solution was made up to a volume of about 200 cc., filtered, end coofed to 10°G. in an ice bath. To this clear solution was added 0,4 gram of copper sulfate, and a green curdy pre- cipitate formed. !o this alkaline mixture was added slowly and with stirring the cooled solution of the diazonium salt of diphenyl ether. Considerable frothing ensued, the froth being scraped off the top as it rose above the sides of the beaker. The temperature of the re- acting mixture was maintained at 10°C. When the entire amount of the diazo solution .had been added, the mixture was allowed to stand until the evolution of nitrogen had ceased. The copper coupling reagent was then filtered from the solution, and the clear filtrate . -14- was acidified with hydrochloric acid, and allowed to stand, finely divided crystalline precipitate formed after a short time. This was filtered off from the large volume of liquid, dried upon a clay plate, and several attempts were made to ascertain its melt- ing point. It did not melt below 300°C. The dried powder had a light brownish-yellow color, so an attempt was made to purify it by means of two alcohol crystallizations. jx lighter colored product was obtained, but it did not melt below 500°^. The yield was only 25 p of the theory. An analysis for arsenic was made upon the re- crystallized product. Two samples showed 20.62y ana 21.25 y re- spectively. The theoretical percentage is 25.51/0. The light col- ored product obtained was evidently quite impure. The lack of time prevented further investigation concerning the preparation and properties of this compound. Summary . 1. A satisfactory method has been devel- oped for the preparation of alkali phenolates from phenol, alco- hol, and an alkali hydroxide. 2. In the preparation of p-nitro-chlorben- zene under ordinary conditions of nitration, the para compound is obtained in much smaller quantities than the ortho compound. Vig- orous stirring and the maintaining of a uniformly low temperature does not increase the yield of the para compound. 3. Mono -nitro -diphenyl ether is best pre- pared from potassium phenolate and p-nitro-bromrbenzene. The sub- limed crystals forming at the top of the flask in the preparation of ' -15- this compound are probably not pure mono-nitro-diphenyl ether as Jones and C 0 ok said they were f 14), hut are merely the original nitro oenzene derivative. also, the pure product probably has not the melting point of 12a. o J. us stated by Jones and Cook, but has a melting point very close to 61°C. as stated by Hauessermaim and Deichmann f 17 ) . a • -ri saving in time is realized in the re- paration of mono -amino -diphenyl ether if an iron reduction is em- o ployed ratner than a reduction with tin and hydrochloric acid. • -art s reaction for the replacement of o.ie diazo group with the arsonic acid group, with the aid of a cop- per salt as a coupling agent is applicable to arsonic acid deriva- tives of the diphenyl ether series. ' Be for one os . 1. Witt, Berichte, 1909,42,2955. 2. Morgan, Gilbert 1. : Organic Compounds of arsenic and antimony, 1918. 5. Bart’s Reaction: Eng. '. 568, 1911, D,ui._ , 250264. 4. Jacobs, Beidelberger , and Bolf: on nitro and amino aryl arsonic acids: J.O.C. 40,2, 1918, - 1580-1590. 5. Ber. 44,5302, 1911. 6. Ibid. 47, 1006, 1316, 1914. 7. Benda: J.Prakt .Chem. 95, 74-106, 1917. J.Chem.Soc. 112,1, 599-601. 8. Chem. age P.Y. 28, 590-1, 1920. 9. A. Schmidt , H.Gr, Heysler, and Bodebeul: -nn. 421, 159-74 1921. 10. littermann: Piss. Botich, 1911. 11. G.2. Bobertson and J. Stieglitz: J. Am. Chem. Soc . 45, 179-81, 1921. 12. J.Chem.Soc. 117,865-75, 1920. 15. Brit. p. 142,947, Feb . 20,1919 . 14. J.-mer.Chem. Soc . Vol. 58, pt.2, - .1545, 1916. 15. J. Indust, and Eng. Chem. Sept. 1919, -.825. Badische 1 Bochst. 16. Bart’s Beaction: D.B.P. 268172. 17. Kauessermann and Deichmann: Ber. 49, 1446, 1896.