IRortb western EVANSTON, ILL Some Organic Compounds of Mercury A DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS OF NORTHWESTERN UNIVERSITY FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF CHEMISTRY BY EDMUND BURRUS MIDDLETON EASTON, PA.: PRESS OF THE ESCHENBACH PRINTING CO. 1922 TRortbweetern EVANSTON, Il,L. Some Organic Compounds of Mercury A DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS OF NORTHWESTERN UNIVERSITY FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF CHEMISTRY BY EDMUND BURRUS EASTON, PA.: PRESS OF THE ESCHENBACH PRINTING CO. 1922 SOME ORGANIC COMPOUNDS OF MERCURY 1 ' 2 Very few mercury derivatives of aromatic esters are known. These have been prepared by direct mercurization of the esters by mercuric ace- tate. Methyl benzoate gives mono- and dimercurated compounds, the structures of which have not been definitely established. 3 0-Chloromer- curibenzoic methyl ester has been obtained from methyl alcohol and sul- fidemercuri-benzoyl chloride. 4 The esters of ortho- and para-ammo- benzoic acids and their mono- and di-alkyl derivatives give mono- and di- mercurated compounds. 5 Esters of salicylic acid react with mercuric acetate giving mono-mercurated compounds. 6 Mercurated acid chlorides were unknown until recently, when 0-chloro- mercuri-benzoyl chloride was prepared from thionyl chloride and the 1 Presented at the Rochester Meeting of the American Chemical Society, April 1921. 2 This work was done under a grant from the United States Interdepartmental Social Hygiene Board, Washington, D. C., Dr. Valeria H. Parker, Secretary. Some of the organic mercury compounds prepared will be tested for their pharmaceutical value by Dr. A. S. Loevenhart of the University of Wisconsin. 3 Schoeller and Schrauth, Ber., 53, 636 (1920). 4 Sachs, ibdi., 53, 1741 (1920). 5 Schoeller and Hueter, ibid., 47, 1930 (1914). Schoeller, Schrauth and Liese, ibid., 52 1777 (1919). Ref. 3, p. 634. 6 Ref. 3. p. 639. 602603 l v V.^T^ -.:..:, ,-.- 4 anhydride of 0-hydroxymercuri-benzoic acid. 4 Undoubtedly, it was thought that halides of phosphorus could not be used for making acid chlorides containing mercury, as it has long been known that these halides react with organomercury compounds with the elimination of the mercury. 7 During the first part of the present work thionyl chloride was used, but it was soon found possible to use phosphorus pentachloride without re- moving the mercury from the molecule. The present paper is a report of the preparation and properties of a number of esters and other derivatives of mercurated ^-nitrobenzoic acid obtained from the corresponding mercurated acid chloride. When the mercuric salt of ^-nitrobenzoic acid is heated to 200 it gives the inner anhydride of o-hydroxymercuri-^-nitro-benzoic acid. 8 The anhydride suspended in chloroform reacts with phosphorus pentachloride to give the desired acid chloride. Hg O 2 N It was found difficult to obtain the acid chloride in a form pure enough for analysis. The derivatives were prepared directly from the crude product. The w-butyl, w-propyl, isopropyl, ethyl and methyl esters were made from the alcohols and the crude chloride. The melting points of these compounds increase regularly from the w-butyl ester to the methyl ester. The acid chloride was also treated with ethylene chlorohydrine, ethylene bromohydrine, and diethylamino-ethyl alcohol. Esters were formed in each case, but only the first of these has as yet been obtained in pure form. The chloride reacted normally with aniline giving an ani- lide. The action of inorganic iodides on the mercurated esters was studied. The reaction consists in the change of the compounds of the type, RHgX, to those of the type, R2Hg. The mercurated esters thus resemble the mercurated hydrocarbons, the mercurated dimethylanilines, and the acetylated mercury phenols, rather than the free mercury phenols from which the mercury is entirely removed by the action of inorganic halides. 9 An equivalent amount of alkali is formed during this removal of mercury. In the case of the mercurated esters no alkali is formed. The reaction is as follows 7 Buckton, Ann., 108, 105 (1858). Cahours, Ber., 6, 568 (1875). Michaelis, Ann., 293, 196, 248, 303 (1896). 8 Blumenthal, Biochem. Z., 32, 60 (1911). Whitmore, J. Am. Chem. Soc. 41, 1841 (1919). Whitmore and Middleton, ibid., 43, 622 (1921). C0 2 R C0 2 R C0 2 R + 4 KI = ,/\ -- Hg -- /\ + K 2 HgI 4 + 2 KC1. NO 2 NO 2 NO 2 These derivatives of mercury diphenyl are less soluble than the corre- sponding chlorides and their melting points are higher. They react in the usual way with mercuric chloride forming the compounds of the type, RHgCl. They can be saponified without breaking the C-Hg linkage. The acid obtained by this process is 0-mercuri-fos(-nitrobenzoic acid), which has been prepared by a regulated alkaline reduction of o-hydroxy- mercuri-p-nitrobenzoic acid. 8 The acid chloride prepared by Sachs was also prepared by means of phosphorus pentachloride. The w-butyl ester prepared from it was identical with that prepared from a sample of the acid chloride made with thionyl chloride. Experimental The mercuric salt of ^-nitrobenzoic acid was prepared from the sodium salt by precipitation with a nearly neutral solution of the calculated amount of mercuric nitrate. The precipitate was washed thoroughly and dried. Fifty g. of the mercuric salt was heated for 3 hours at 200-220 in a small flask immersed in an oil-bath. When samples of more than 100 g. were heated, explosions sometimes occurred. After heating the mix- ture, it was cooled and the ^-nitrobenzoic acid which formed was removed by repeated extractions with small amounts of ether. The residue in- soluble in ether consisted of the nearly pure anhydride of 0-hydroxymer- curi-^-nitrobenzoic acid. C0 2 C 4 H 9 w-Butyl Ester of 0-Chloromercuri--nitrobenzoic acid, ' . Ten g. of NO 2 the anhydride was suspended in 100 cc. of chloroform and treated in the cold with 7 g. of phosphorus pentachloride. Vigorous action ensued. The mixture was then heated under a reflux condenser about 30 minutes. The solution was then cooled and filtered. The precipitate was washed with chloroform to remove phosphorus oxychloride and al- lowed to dry. The dry acid chloride was then treated with 10 cc. of n- butyl alcohol and heated until it completely dissolved As this product cooled, white crystals of the n- butyl ester separated. These are fairly soluble in ethyl alcohol, benzene, chloroform, acetone, ether, and carbon tetrachloride. The product was recrystallized from hot ethyl alcohol until it showed a constant melting point of 125-126 (uncorr.). Nine g. of the ester was obtained from 10 g. of the crude anhydride; yield, 70%. Most of the loss occurs in the conversion of the acid to the acid chloride which is never complete. Analyses. Subs., 0.1754: Hg, 0.0770. Subs., 0.1991, 0.2033: CO 2 , 0.2071, 0.2146. Calc. for C n H 12 O 4 NClHg: C, 28.8; Hg, 43.8. Found: C, 28.4, 28.8; Hg, 43.9. 10 10 The analyses for mercury were carried out by the "gold crucible method" de- w-Propyl Ester. The procedure given above was employed, except that 10 cc. of w-propyl alcohol was used instead of butyl alcohol. The product, after repeated crystallizations from ethyl alcohol, melted at 145-150 . No sharper melting point could be obtained. The ester is moderately soluble in ethyl alcohol, chloroform, ether, carbon tetrachloride, acetone and benzene. Analyses. Subs., 0.1943, 0.1911: Hg, 0.0887, 0.0871. Calc. for C IO H 10 O 4 NClHg: Hg, 45.2. Found: 45.6, 45.6. /sopropyl Ester. The same procedure was used as with the other esters. The purified product melted at 179-180. Analyses. Subs., 0.1981, 0.2089: Hg, 0.0897, 0.0943. Calc. for Ci Hi O 4 NClHg: Hg, 45.2. Found: 45.3, 45.1. Ethyl Ester. The purified product melted at 220-222. Its properties and solu- bilities are similar to those of the other esters. Analyses. Subs., 0.1945, 0.1800: Hg, 0.0899, 0.0842. Calc. for C 9 H 8 O 4 NClHg: Hg, 46.6. Found: 46.2, 46.8. Methyl Ester. The product, purified by crystallization from methyl alcohol, melted at 240-245. Analyses. Subs., 0.2206, 0.2008: Hg, 0.1077, 0.0976. Calc. for CsHeC^NClHg: Hg, 48.2. Found: 48.9, 48.6. Chloro-ethyl Ester. This ester was prepared from the crude acid chloride and ethylene chlorohydrine in the usual way. Its solubilities and properties resembled those of the other esters. Crystallization from ethyl alcohol gave a product melting at 163-164. Analyses. Subs., 0.2010, 0.2023, 0.2323: Hg, 0.0865, 0.0879,0.1000. Calc. for C 9 H 7 05NCl 2 Hg: Hg, 43.2. Found: 43.0, 43.4, 43.1. Attempts at Preparation of the Bromo-ethyl and Alkamine Esters The acid chloride was found to react readily with ethylene bromohydrine and with diethylammo-ethyl alcohol, but no homogeneous product was obtained from either reaction. Further attempts are being made to prepare these esters in a state of purity. Determination of the Position of the Mercury in the Esters When the mercurated esters reacted in the cold with bromine water, they gave products which, after saponification and acidification, were converted into o-bromo-p- nitrobenzoic acid; this was identified by its melting point (163) and by analyses for bromine. Anilide of 0-Chloromercuri-/>-mtrobenzoic Acid. Ten g. of the crude acid chloride was heated with 6 cc. of aniline until solution took place. The anilide separated as the mixture cooled. It was washed free from aniline with benzene and recrystallized from ethyl alcohol. The product was soluble in hot ethyl alcohol, slightly soluble in ether and insoluble in most other organic solvents. Analyses. Subs., 0.2112, 0.2001: Hg, 0.0878, 0.0832. Calc. for C 13 H 9 O 3 N2-ClHg: Hg, 42.0. Found: 41.6, 41.6. CO 2 Bu CO 2 Bu w-Butyl Ester of 0-Mercuri-&(-nitrobenzoic Acid), f NO 2 NO 2 scribed on p. 365 of "Organic Compounds of Mercury" (Chemical Catalog Co., N. Y. C. 1921) by one of us (W.). In the analysis of organic mercury compounds containing nitro groups the heating must be carried out very cautiously to avoid slight explosions which are likely to blow foreign material against the amalgam. Eight g. of the w-butyl ester of o-chloromercuri-/>-nitro-benzoic acid in 100 cc. of ethyl alcohol was refluxed with 5 g. of potassium iodide for 1 hour. As the reaction mixture cooled, the mercuri-fo's compound separated in colorless crystals. The mother liquor contained large amounts of inorganic mercury. The product was recrystallized from ethyl alcohol; m. p., 158; yield, 5 g. or 95%. Its solubilities resembled those of the corresponding chloromercuri compound but were slightly less. Analyses. Subs., 0.2521, 0.1461: Hg, 0.0791, 0.0459. Subs., 0.1781, 0.2214: CO 2 , 0.2585, 0.3240. Calc. for C 22 H 24 O8N 2 Hg: C, 40.9; Hg, 31.1. Found: C, 39.6, 39.9; Hg, 31.4, 31.4. One g. of this compound was heated with 0.43 g. of mercuric chloride (one mol) in 50 cc. of ethyl alcohol for 30 minutes. The corresponding chloromercuri compound, 1.2 g. separated as the product cooled; m. p., 125. The chloride was analyzed. Analysis. Subs., 0.1923: Hg, 0.0839. Calc. for C n H 12 O 4 NClHg: Hg, 43.8. Found: 43.7. Five g. of the ester of the mercuries compound suspended in 100 cc. of ethyl alcohol was heated with 5 g. of sodium hydroxide. When all of the solid had dissolved, the solution was cooled. The sodium salt which separated was collected, dissolved in water, and the solution acidified. The amorphous precipitate was o-mercuri-bis(p- nitrobenzoic acid), 8 as was shown by analyses for mercury. w-Propyl Ester. Seven g. of the corresponding chloromercuri ester was heated under a reflux condenser with 5 g. of potassium iodide in 100 cc. of alcohol for 1 hour. Colorless crystals of the mercuri-bis compound separated as the solution cooled. After recrystallization from ethyl alcohol, it melted at 189; yield 4.6 g., or 92%. Analyses. Subs., 0.1638, 0.1705: Hg, 0.0538, 0.0549. Calc. for C2oH 2 oO8N 2 Hg: Hg, 32.5. Found: 32.8, 32.2. Treatment of this compound with mercuric chloride in alcohol gave the w-propyl ester of o-chloromercuri-/>-nitrobenzoic acid melting at 145-150. Ethyl Ester. This ester was prepared in the same way as were the w-butyl and w-propyl esters and resembled them in properties; m. p., 227-232. Analyses. Subs., 0.1909, 0.1877: Hg, 0.0650, 0.0644. Calc. for C 18 H 16 O 8 N 2 Hg : Hg, 34.1. Found: 34.1,34.3. n-Butyl Ester of o-Chloromercuri-benzoic Acid. Seven g. of the anhydride of o-hydroxymercuri-benzoic acid was treated with 5 g. of phosphorus pentachloride in 50 cc. of chloroform. Vigorous action took place. As soon as this had ceased, the mix- ture was cooled and the acid chloride was collected on a filter. It was washed with chloroform and allowed to dry. The product was heated with 10 g. of w-butyl alcohol until all of it dissolved. After several recrystallizations from alcohol it melted at 115. Two g. of the 0-chloromercuri-benzoyl chloride prepared by the thionyl chloride method 4 was treated with w-butyl alcohol in the same way. The purified product melted at 116. The melting point of the mixture of the two products was not lower. Analysis. Subs., 0.1668: Hg, 0.0813. Calc. for C n H 13 O 2 ClHg: Hg, 48.4. Found: 48.7. Summary 1. Phosphorus pentachloride can be used as well as thionyl chloride for making acid chlorides of mercurated aromatic acids. 2. The acid chloride of o-chloromercuri-p-nitrobenzoic acid was used to prepare the following esters of the acid: methyl, ethyl, w-propyl, iso- propyl and w-butyl. 8 3. These compounds react with inorganic iodides to form the corre- sponding compounds of the type, R 2 Hg. 4. These compounds can be saponified without breaking the C-Hg linkage. This work was carried out under the direction of Professor Frank C. Whitmore. The author desires to thank him for his advice and criticism. (Reprinted from the Journal of the American Chemical Society, Vol. XLIII. No. 3. March. 1921.) [CONTRIBUTION FROM THB CHEMICAL LABORATORY OF NORTHWESTERN UNIVERSITY.] REACTION OF ALKALI HALIDES WITH MERCURY DERIVATIVES OF PHENOL. 1 BY F. C. WHITMORE AND EDMUND BURRUS MIDDLETON. Received November 22, 1920. Mercury derivatives of phenol lose their mercury quantitatively when treated with a solution of potassium iodide. Ordinarily, an aromatic mercury compound does not react with iodides to give mercuric iodide. Under some conditions, one half of the mercury is removed as the iodide and the other half remains combined in a derivative of mercury diphenyl, 2R-Hg-I + 2KI = K 2 HgI 4 -f- R 2 Hg. In a study of the mercury deriv- atives of ^-bromo-dimethylaniline, 2 it was found that the reaction of potassium iodide with 5-bromo-2-dimethylamino-phenylmercuric acetate gave a considerable amount of ^-bromo-dimethylaniline as well as the expected mercury diphenyl derivative. The formation of metallic mer- cury during the reaction made it appear that the alcohol or some other substance was acting as a reducing agent. However, this could not explain the formation of all of the bromo-dimethylaniline, since the amount of this substance produced was greater than the free mercury would require. A search through the literature revealed a number of cases in which mercury attached to carbon is replaced by hydrogen under the influence of iodide solutions. While this reaction is universal for Hg-N compounds, it is unusual for Hg-C compounds. Since there is undoubtedly some relation between the therapeutic value of mercury carbon compounds and the stability of the Hg-C linkage, it seemed desirable to study the conditions under which this linkage between mer- cury and carbon is broken by inorganic halides. Biilmann found that mercury derivatives of malonic acid and of its esters 3 when treated with potassium iodide solution yield mercuric iodide and one molecule of potassium hydroxide for every Hg-C linkage. With potassium iodide mercury is removed in a different way from the products of the action of mercuric salts upon various unsaturated acids. 4 In this case the original unsaturated acid is recovered. The difference in the 2 reactions may be shown by the equations R-Hg-I + SKI + H 2 O = RH + K 2 HgI 4 + KOH R-CHOH-CHHgI-CO 2 K + 3KI = R-CH = CH-CO 2 K + K 2 HgI 4 + KOH. 1 Part of this work was done under a grant from the U. S. Interdepartmental Social Hygiene Board, Dr. T. A. Storey, Secretary. Presented before the Organic Division of the American Chemical Society at the Chicago Meeting, September 1920. 2 THIS JOURNAL, 41, 1851 (1919). Biilmann, Ber., 35, 2581 (1902); 42, 1070 (1909). 4 Biilmann, ibid., 35, 2571 (1902); 43, 568 (1910); also compare Manchot, Ann., 420, 183 (1920). 620 $. C. WHITMORE AND EDMUND BURRUS MIDDLETON. In the second case the replacement of the mercury by hydrogen is ac- companied by, or followed by, the loss of water. The mercury derivative of cyano-acetic acid 1 behaves in a manner similar to that of the mercury malonic derivatives. The mercury derivative of camphor 2 is said to be "decomposed" rapidly by an acetone solution of potassium iodide. In the aromatic series a few cases of this replacement are recorded. Dimroth found that ^-aminophenylmercuric acetate, 3 when treated with potassium iodide gave a small amount of inorganic mercury. This may be due to the formation of mercuric iodide during the formation of the mercury diphenyl derivative, or during a splitting of the Hg-C linkage, accompanied by the formation of aniline and alkali. Pesci found that salts of 0-(chloromercuri)benzoic acid 4 when treated with sodium halides give sodium benzoate, mercuric halide, and sodium hydroxide. 2-5-Cresylmercuric acetate 5 is said to be "decomposed" by potassium iodide. Brieger and Schulemann in their exhaustive study of the mer- curation of the various naphthalene intermediates 6 of the coal tar dye industry found that the mercurated naphthols are very sensitive to alkali halides. In some cases they titrated the alkali formed and drew conclu- sions as to the completeness of the splitting of the Hg-C linkage. They found that potassium iodide gives a quantitative replacement, while the bromide and chloride give it to a decreasing extent. In other cases they did not determine the alkali formed, but studied the "loosening" effect of the halide by treating with sulfides. In many instances, the pure mer- cury compound gave no action with ammonium sulfide, but, when treated with potassium iodide and then with the sulfide, gave mercuric sulfide. The bromide and chloride of potassium had a similar but weaker effect. Brieger and Schulemann found that the mercurated naphthylamines were split much less readily than the corresponding naphthols. In view of the many cases of this peculiar replacement of organic mer- cury, and the lack of details, it seemed desirable to study the reaction with some substances simpler than the complicated intermediates used by Brieger and Schulemann. The mercurated phenols 7 prepared by Dim- roth offered an ideal subject for the study. Dimroth's method of treating a solution of phenol with mercuric acetate solution was discarded because of the large amount of dimercurated product formed. It was found that phenol, without a solvent, heated 1 Petterson, /. prakt. Chem. [2] 86, 458 (1912). * Marsh and Fleming-Struthers, /. Chem. Soc., 95, 1777 (1909). 3 Z. anorg. Chem., 33, 314 (1903). Pesci, Gazz. chim. ital., 32, II, 277 (1902); Centralbl, 1902, II, 1454. 6 Dimroth, Ber., 35, 2853 (1902). Compare Brieger and Schulemann, J. prakt. Chem., [2] 89, 104 (1914). 6 Ibid ., 97 ff. 7 Habilitationsschr., Tubingen, 1900; Centralbl., 1901, I, 452; Ber., 35, 2855 (1902). MERCURY DERIVATIVES OP PHENOL. 621 with mercuric acetate on the steam-bath gives a mixture of the ortho and para compounds free from the disubstituted product. These were sep- arated by Dimroth's method of forming the chlorides; the ^-hydroxy- phenylmercuric chloride is insoluble in hot water, while the ortho com- pound is soluble. At temperatures above that of the steam-bath, the total yield was decreased somewhat, but the amount of ortho compound increased slightly. The 3 mercurated phenols were boiled with aqueous potassium iodide. In each case the solid soon dissolved and the solution became alkaline. After boiling for 30 minutes the alkali was titrated with stand- ard acid and phenolphthalein. The ortho and para compounds gave almost one molecule of alkali while the di- compound gave almost 2. HO-C 6 H 4 -HgCl + KI + H 2 = HO-C 6 H 5 + K 2 HgI 4 + KOH + KC1. The dimercuric chloride compound would give 2 molecules of potassium hydroxide. When potassium bromide was used in place of the iodide, only a small amount of alkali was formed. Potassium chloride gave no alkali even on prolonged boiling. It seemed desirable to find out whether this unusual removal of mer- cury from the aromatic nucleus depended on the presence of the phenolic hydroxyl. To answer this question the acetyl derivatives of the o- and p- hydroxyphenylmercuric chlorides were prepared and treated with potas- sium iodide. There was no splitting of the Hg-C linkage in these cases. The solutions remained neutral. If splitting had occurred the alkali formed would probably have saponified the phenyl acetate to form sodium acetate and free phenol. No phenol was obtained as was shown by dis- tillation of the neutral mixture with steam and a test of the distillate with ferric chloride. The acetylated 0-hydroxyphenylmercuric chloride reacted with aqueous potassium iodide to form the organomercuric iodide. The hot mother liquor from this iodide gave a small amount of the cor- responding mercury diphenyl derivative, o,o / -mercuri-bis(phenyl acetate). The same reaction, carried out in alcohol solution, gave only the iodide. The acetylated ^-hydroxyphenylmercuric chloride gave only the corres- ponding iodide. As the yield of the substituted mercury diphenyl is often larger with sodium thiosulfate than with potassium iodide, the former reaction was tried with the acetylated mercury phenols. In each case, a fair yield of the mercury diphenyl derivative was obtained. The proof of the struc- ture of these compounds lies in the fact that they react quantitatively with mercuric chloride to give the original acetylated hydroxyphenyl- mercuric chlorides. 2CH 3 CO-OC 6 H 4 -HgCl + 2Na 2 S2O 3 = (CHsCO-OCeH^Hg + Na 2 Hg(S2O3) 2 + 2NaCl. (CH3CO-OC 6 H 4 ) 2 Hg + HgCl 2 = 2CH 3 CO-OC 6 H 4 -HgCl. 622 F. C. WHITMORE AND EDMUND BURRUS MIDDLETON. Dirnroth was able to change the 0-hydroxyphenylmercuric chloride to the corresponding mercury diphenyl derivative but did not carry out the reaction with the para compound. Dimroth's work was repeated and confirmed. It seemed possible that the missing para mercury di- phenyl derivative might be made by saponifying the corresponding acetylated substance. When this was tried the product was found to be a monophenylmercuric derivative. In other words, one of the phenyl groups had been removed from the mercury by the action of hot sodium hydroxide. Apparently this is a new method of splitting a Hg-C linkage. It is another example of the "loosening" effect of hydroxyl or, in this case of the ONa group, on a mercury atom attached to the same nucleus. The reactions involved may be written thus : (CH 3 CO-OC 6 H 4 -) 3 Hg+4NaOH = (NaO-C 6 H4-) 2 Hg+2CH 3 CO2Na+2H 2 O 2(NaO-C 6 H4-GHg-j-H 2 O = NaO-C 6 H4-HgOH+C 6 H5ONa Neutralization with dil. acetic acid precipitated (HO-C 6 H 4 -Hg)2O in- stead of the corresponding hydroxide. 1 An analogous reaction occurs and a similar product is obtained with the acetylated ortho diphenyl derivative. Both the complex organomercuric oxides were converted to the original chlorides by treatment with acetic acid and sodium chloride. The same conversion was brought about by treatment with ethyl acetate and then with sodium chloride solution. 2 All the organic mercury com- pounds studied reacted with ammonium sulfide only on standing. They reacted slowly with cold cone, hydrochloric acid, but rapidly with the hot acid to give inorganic mercury salts which formed an immediate pre- cipitate with hydrogen sulfide. Experimental. Preparation of the 0- and ^-Hydroxyphenylmercuric Chlorides. Twelve g. of phenol (about 1.5 molecules) was heated on the steam-bath and 25 g. of mercuric acetate was added gradually while the mixture was stirred constantly. When all the acetate had dissolved, boiling water was added and the mixture was boiled for a few minutes. Then a hot solution of 5 g. of sodium chloride was added. The />-hydroxyphenyl- mercuric chloride precipitated at once. The mixture was filtered while hot. The solution, on standing, deposited crystals of the ortho compound. The properties of these substances agreed with those recorded by Dimroth. When the preparation was carried out as described, no dimercury compound was formed. This was proved by the complete solubility of the mixture in boiling water. The amounts of ortho and para compounds formed varied only slightly with the temperature of reaction. With 25-g. portions of mercuric acetate (about 85% pure), the following amounts of para and ortho compounds were obtained, at 100, 18 g. of para and 7 g. of ortho; at 125, 16 g. of para and 8 g. of ortho; at 150, 14 g. of para and 8 g. of ortho. Preparation and Properties of the Acetyl Derivatives of the Hydroxyphenyl- mercuric Chlorides. Fourteen g. of the o-hydroxyphenylmercuric chloride was treated with a slight excess of acetyl chloride (3 cc.) and warmed gently. After the evolution 1 Compare Dimroth, Ber., 35, 2854 (1902). 2 Compare THIS JOURNAL, 41, 1854, Summary, 3 (1921). MERCURY DERIVATIVES OF PHENOL. 623 of hydrochloric acid had ceased, the substance was pressed on a porous plate and then washed many times with water. Twelve g. of the acetyl derivative was obtained (about an 80% yield). The para compound was prepared in a similar way. Melting points (uncorr.): ortho, 170-1; para, 235. Analyses. Calc. for C 8 H 7 OClHg: Hg, 54.05. Found: ortho, 54.1, 54.0, 54.0; para, 53.8, 53.5. Reaction of Potassium Iodide with the Mercurated Phenols. When the o-hydroxy- phenyl mercuric chloride, the corresponding para compound, and the o,-diacet- oxymercoriphenol were boiled with excess of potassium iodide solution they dissolved, the solmtions became alkaline, and phenol and inorganic mercury compounds were formed. The alkali was titrated with standard acid. The procedure was as follows. 1 g. of the mercury compound was boiled for half an hour with 50 cc. of water and 2 g. of potassium iodide. Water was added to replace that lost by evaporation. The base was then titrated with 0.1 N sulfuric acid. One g. of the 0-hydroxyphenylmercuric chloride gave 30.12 cc. of 0.1 N potassium hydroxide, while that calculated was 31.90. One g. of the para compound gave 29.12 cc. of 0.1 N potassium hydroxide, as compared with calculated 31.90 cc. One g. of the dimercury acetate compound gave 32.50 cc. of 0.1 N hydroxide, compared with 32.6 cc. calculated for 2 molecules. An experiment was tried with the ortho compound in which potassium bromide or chloride was used instead of the iodide. The compound boiled with the chloride gave no alkali. Long boiling of it with the bromide gave only a slight alkalinity. Similar results were obtained with the para and with the di-compounds. Reaction of Potassium Iodide with the Acetylated Compounds. When the acetyl derivative of the o- or ^-hydroxyphenylmercuric chlorides was boiled with potassium iodide solution, no alkali r phenol was formed. Thus, 1.5 g. of the ortho acetylated compound was boiled for one hour with 50 cc. of water and 2 g. of potassium iodide. The solution was still neutral. The solution was distilled with steam and the distillate was tested with ferric chloride. No color resulted. When the aqueous nitrate from the organomercuric iodide was cooled, it yielded 0.2 g. of white needle shaped crystals melting at 125* This substance was proved to be the mercury diphenyl derivative, mercury di-(o hydroxyphenyl acetate), (CH 3 CO-OC 6 H 4 -)2Hg. The yield was only about 20%. The ara-acetylated compound is changed to the organomercuric iodide only after long boiling with potassium iodide. Reaction of Sodium Thiosulfate with the Acetylated Compounds. Seven g. of the ortho acetyl derivative was dissolved in a thiosulfate solution containing 15 g. of the crystalline salt in 100 cc. of water. The mercury compound dissolved fairly readily to give a clear solution. As this solution stood, crystals of the mercury diphenyl compound separated. After 3 days, 3.6 g. of the o, o'-mercuribisphenol diacetate had separated as white needles, m. p. 125 . Yield, about 80%. They are slightly soluble, on heating, in alcohol, in benzene, and in chloroform; very slightly soluble in ether. Analyses. Calc. for Ci 6 H 14 O 4 Hg: Hg, 42.62. Found: 42.7, 42.0. Similarly, the para acetylated compound was treated with thiosulfate. The para diphenyl derivative separated from the thiosulfate solution as white crystals, m. p. 172-3, much more slowly than did the ortho compound. The yield was poorer; 10 g. of the chloride gave only 3 g. of the diphenyl compound, about a 50% yield. Analyses. Calc. for Ci 6 Hi 4 O 4 Hg: Hg, 42.62. Found: 42.4, 42.3. Reaction of Mercuric Chloride with the Acetylated Diphenyl Derivatives. The structure of the diphenyl derivatives was proved by splitting them with mercuric chloride to form the original chlorides. One g. of the ortho diphenyl derivative was boiled with 50 cc. of water containing 0.5 g. of mercuric chloride and yielded 1.4 g. of the ortho CH 3 CO-OC 6 H 4 -HgCl, m. p. 170. Similarly, the para diphenyl compound, gave the original chloride (m. p. 235), quantitatively. 624 F. C. WHITMORE AND EDMUND BURRUS MIDDLETON. Reaction of the Acetylated Mercury Compounds with Sodium Hydroxide. Three g. of [the ortho acetylated mercury diphenyl compound was boiled for 20 minutes with 50 cc. of 5% sodium hydroxide. The solution was cooled and made exactly neutral with dil. acetic acid. One and seven-tenths g. of a white amorphous substance separated. It did not melt, but darkened at a high temperature. Analyses indicated that it was the oxide obtained by Dimroth, di(hydroxyphenylmer curie) oxide. Analyses. Calc. for C 12 H 10 O 3 Hg 2 : Hg, 66.5. Found: Hg, 67.0, 66.7, 66.2. When treated with dil. acetic acid and sodium chloride it gave the original chloride, hydroxyphenylmercuric chloride. When the oxide was boiled with ethyl acetate it dissolved readily. When this solution was boiled with sodium chloride solution the original chloride was formed. The acetylated para mercury diphenyl compound was split in the same way by boiling with dilute sodium hydroxide. A similar complex oxide was formed. Like its isomer it was amorphous and did not melt. Analyses. Calc. for C 12 H 10 O 3 Hg 2 : Hg, 66.5. Found: Hg, 66.8, 67.0. This complex oxide was changed to the ^-hydroxyphenylmercuric chloride by treatment with dilute acetic acid and sodium chloride, and, also, by treatment with ethyl acetate and sodium chloride. Reaction of the Acetylated Compounds with Sulfides and with Acids. The ortho and para acetylated hydroxyphenylmercuric chlorides suspended in water and treated with hydrogen sulfide for 15 minutes gave no mercuric sulfide. After contact with ammonium sulfide for about half an hour, they commenced to blacken. The free mer- cury phenols acted a little more rapidly. The acetylated mercury diphenyl com- pounds gave no action with ammonium sulfide in less than 3 days; then a red precipitate began to form. The acetylated hydroxyphenylmercuric chlorides treated with cone, hydrochloric acid and hydrogen sulfide showed no reaction. After standing for half an hour, or if they were heated, mercuric sulfide was formed. The acetylated mercury diphenyl compounds treated with cone, hydrochloric acid and hydrogen sulfide gave no mer- curic sulfide, until the mixture had stood for about an hour or had been heated. Summary. 1. Mercuric acetate reacts with an excess of phenol in the absence of a solvent to form only the ortho and para mercurated phenols. This differs from the action in water which gives a large amount of the di- product even in the presence of a large excess of phenol. 2. The hydroxyphenylmercuric chlorides and the corresponding di- mercury acetate are split by iodides; mercuric iodide, phenol, and a base are formed. Bromides cause a partial splitting, chlorides none at all. 3. The acetylated compounds are not split by potassium iodide in the way that the phenols are. They give the organomercuric iodides and, in the case of the ortho compound, a small amount of the corresponding mer- cury diphenyl derivative. 4. Both of the acetylated chlorides react with cone, sodium thiosulfate solution to give the corresponding acetylated mercury diphenols. 5. The acetylated mercury diphenols, when treated with dil. sodium hydroxide, not only lose the acetyl groups but suffer a splitting of the Hg-C linkage which leaves a monophenylmercuric derivative. This, ap- parently, is a new method of breaking an Hg-C bond. EVANSTON, lU,. [Reprinted from the Journal of the American Chemical Society, Vol. XLV. No. 7. July, 1923.] [CONTRIBUTION FROM THE CHEMICAL LABORATORY OF THE COLLEGE OF LIBERAL ARTS OF NORTHWESTERN UNIVERSITY] SOME MERCURY DERIVATIVES OF PHENOL ETHERS 1 BY FRANK C. WHITMORE AND EDMUND BURRUS MiDDLETON 2 Received February 23, 1923 In an earlier paper 3 it was shown that mercurated phenols react with iodides of alkali metals to give the original phenols, inorganic mercury compounds and 1 equivalent of alkali for each carbon-mercury linkage broken. When, however, the hydroxyl group is protected by acylation iodides react in quite a different way giving mercuri-bis compounds and inorganic mercury compounds but not alkali. The two processes may be illustrated as follows. HO C 6 H 4 Hgl + 3 KI + H 2 > C 6 H 6 OH + K 2 HgI 4 + KOH 2 AcO C 6 H 4 Hgl + 2 KI > (AcO C 6 H 4 ) 2 Hg -f- K 2 HgI 4 The present work was undertaken to determine the effect of replacing the phenolic hydrogen by an alkyl group instead of an acyl group. An observation made by Dimroth 4 indicated that the effect of the 2 groups might be similar. In determining the structure of 0-chloromercuri-phenol, he treated it with ethyl iodide in alkaline alcoholic solution to prepare the known o-phenetylmer curie iodide. Besides the desired product he ob- tained a good yield of 0-mercury-diphenetyl. Since sodium iodide is formed in the reaction it seemed reasonable that it might change the mercurated phenetole first formed to the mercuri-bis compound. Dim- roth's results may then be formulated as follows. NaO C 6 H 4 HgCl + RI > RO C 6 H 4 HgCl -f Nal 2 RO C 6 H 4 HgCl + 4 Nal > (RO C 6 H 4 ) 2 Hg + Na 2 HgI 4 + 2 NaCl In order to test this theory and to study further the effect of protecting a phenolic hydroxyl group upon the stability of the carbon-mercury linkage, the action of potassium iodide on mercurated phenol ethers was studied, lodomercuri-anisoles and -phenetoles were prepared by the method of Dimroth. 4 As the oriho mercurated compounds are much more soluble than the para compounds, the study was limited to the former. When an alcoholic solution of o-iodomercuri-anisole or of 0-iodomercuri-phenetole is refluxed with potassium iodide, no splitting of the carbon-mercury linkage takes place as no alkali is formed. o-Mercury-dianisyl or 0-mercury- diphenetyl is obtained in good yield. The mother liquors contain large amounts of inorganic mercury compounds. Potassium thiocyanate acts 1 Presented at the Rochester Meeting of the American Chemical Society, April, 1921. 2 Research Fellow under a grant from the U. S. Interdepartmental Social Hygiene Board, General M. W. Ireland, Chairman. Some of the organic mercury compounds related to those studied are being investigated pharmacologically under the direction of Dr. A. S. Loevenhart of the Department of Pharmacology of the University of Wisconsin. 3 THIS JOURNAL, 43, 622 (1921). 4 Dimroth, Ber., 32, 763 (1899). 1754 FRANK C. WHITMORE AND KDMUND B. MIDDU3TON Vol. 45 like potassium iodide but gives poorer yields of the mercuri-bis compounds. The para mercurated phenol ethers react to some extent with potassium iodide or with potassium thiocyanate; some inorganic mercury is formed. No alkali is found. The corresponding mercuri-bis compounds are not obtainable in a pure state by these reactions. Sodium thiosulfate is the most convenient reagent for making the mercuri-bis compounds of the phenol ethers. The -iodomercuri com- pounds dissolve readily in it giving solutions from which the mercuri-bis compounds separate on standing. o-Mercury-dianisyl and o-mercury-diphenetyl react normally with mer- curic chloride; quantitative yields of the chloromercuri compounds are obtained. Experimental Part Preparation of o- and -Iodomercuri-phenetoles. A mixture of 5 g. of o-chloro- rnercuri-phenol 3 in 50 cc. of 50% ethyl alcohol, 0.7 g. of sodium hydroxide, and 3.5 g. of ethyl iodide is heated gently for 1 hour. A small amount of o-mercury-diphenetyl separates as the solution cools. This is removed and the filtrate is diluted with water to precipitate the o-iodomercuri-phenetole which is recrystallized from alcohol; yield, 7 g. The para compound is prepared in a similar way. Five g. of />-chloromercuri- phenol gives 5 g. of a mixture of the corresponding iodomercuri and mercuri-bis-com- pounds which is difficult to separate. Because the ortho compounds are obtained more easily, the experiments with potassium iodide, with thiocyanate, and with thiosulfate were carried out with o-iodomercuri-phenetole and 0-iodomercuri-anisole. Preparation of o-Iodomercuri-anisole. Eight g. of o-chloromercuri-phenol, 1 g. of sodium hydroxide, 50 cc. of alcohol, and 3 g. of methyl iodide are heated for half an hour. About 1 g. of 0-mercury-dianisyl separates as the solution cools. Dilution of the mother liquor with water gives 7 g. of the iodomercuri compound. Reaction of Potassium Iodide with o-Iodomercuri-anisole and with o-Iodomercuri- phenetole. Four g. of o-iodomercuri-anisole, recrystallized from alcohol, is heated under a reflux condenser for 6 hours with 3 g. of potassium iodide and 50 cc. of alcohol. When the product is cooled and diluted somewhat the o-mercury-dianisyl is precipitated. It is recrystallized from alcohol; yield, 1.5 g. ; m. p., 108. The filtrate from the reaction mixture is neutral and gives an immediate precipitate with hydrogen sulfide. A solution of 2 g. of o-iodomercuri-phenetole in 50 cc. of alcohol together with 2 g. of potassium iodide is refluxed for 1 hour. When this product is cooled and diluted with water, 1.5 g. of 0-mercury-diphenetyl separates. After crystallization from alcohol it melts at 81 . The filtrate is not alkaline. It contains inorganic mercury compounds. Reaction of Potassium Thiocyanate with the o-Iodomercuri-phenol Ethers. A mixture of 2 g. of o-iodomercuri-anisole, 2 g. of potassium thiocyanate and 50 cc. of al- cohol was heated under a reflux condenser for 3 hours. The product, cooled and diluted, gave 1.5 g. of the mercuri-bis compound. Recrystallization from alcohol raised the melting point only to 75-80. The filtrate contains inorganic mercury compounds but is neutral. A mixture of 1.6 g. of o-iodomercuri-phenetole, 2 g. of potassium iodide and 50 cc. of alcohol, heated under a reflux condenser for 3 hours gives 0.8 g. of the mercuri-bis compound melting at 80 after several crystallizations from alcohol. Reaction of Sodium Thiosulfate with the o-Iodomercuri-phenol ethers. Two g. of o-iodomercuri-phenetole dissolved in a solution of 4 g. of sodium thiosulfate in 50 cc. of water deposits 1.2 g. of the mercuri-bis compound on standing; m. p., 81-83. July, 1923 MERCURY DERIVATIVES OF PHENOL ETHERS 1755 Similarly, o-iodomercuri-anisole gives the mercuri-bis compound melting at 108. Reaction of the -Iodomercuri-phenol Ethers with Potassium Iodide and with Potassium Thiocyanate. The reactions between these substances apparently lead to the formation of mercuri-bis compounds, as the filtrates contain inorganic mercury and are not alkaline. However, the products are very difficult to purify. Reaction of Mercuric Chloride with the Mercuri-bis-phenol Ethers.-MDne g. of 0-mercury-dianisyl is heated with 0.7 g. of mercuric chloride in 25 cc. of alcohol for 15 minutes. The chloride deposits on cooling, and is recrystallized from alcohol; m. p., 177-178. Dimroth obtained the same compound in small amount by direct mercura- tion of anisole. He gives the melting point as 173-174. Similarly, o-mercury-diphenetyl reacts with mercuric chloride to give pure o-chloro- mercuri-phenetole . Summary 1. Protection of the hydroxyl groups in mercurated phenols by alkyla- tion has the same effect as protection by acylation, that is, the stability of the carbon-mercury linkage to iodides, thiocyanates, and to thio- sulfates is increased. 2. Mercurated phenol ethers react with iodides, with thiocyanates, and with thiosulfates to form the corresponding mercuri-bis compounds giving solutions which contain inorganic mercury but no alkali, showing that the protection of the phenolic hydroxyl has prevented the splitting of the carbon -mercury linkage with the accompanying formation of alkali which occurs with the mercurated phenols. 3. The formation of the mercuri-bis compounds takes place much more readily in the case of the ortho compounds than with the para compounds. EVANSTON, ILLINOIS [Reprinted from The Journal of the American Chemical Society, Vol. XLV, No. 5. May, 1923.] [CONTRIBUTION PROM THE CHEMICAL LABORATORY OP THE COLLEGE OP LIBERAL ARTS OF NORTHWESTERN UNIVERSITY] MERCURY DERIVATIVES OF SALICYLALDEHYDE AND THE NITRO-SALICYLALDEHYDES 1 BY FRANK C. WHITMORE AND EDMUND BURRUS MmoLETON 2 Received February 15, 1923 s Aromatic aldehydes cannot, as a rule, be mercurated by mercuric acetate because of its oxidizing action. At the time the present work was done the only mercurated aromatic aldehyde was a mercury vanillin of un- determined structure. 3 More recently the 3 hydroxybenzaldehydes have been mercurated. 1 * Definite mercuration products have also been obtained from vanillin. 4 Salicylaldehyde was chosen for the present study because of its resistance to oxidation and because of the activating effect of the phenolic hydroxyl. Salicylaldehyde reacts readily with two molecular proportions of mer- curic acetate in alcohol to form 3,5-diacetoxymercuri-salicylaldehyde. No oxidation takes place, as shown by the absence of mercurous acetate and metallic mercury from the products. The dichloromercuri compound is made in the usual way from an acetic acid solution of the acetate and a chloride solution. Even when only 1 molecular proportion of mercuric acetate is used the chief product is the dimercurated compound, although a small amount of a monomercurated product can be obtained from the 1 Presented at the Birmingham Meeting of the American Chemical Society, April, 1922. Since the presentation of this paper an article has appeared by Henry and Sharp on the mercury derivatives of the three hydroxybenzaldehydes. (a) /. Chem. 5oc., 121, 1055 (1922). 2 Research Fellow under a grant from the U. S. Interdepartmental Social Hygiene Board, General M. W. Ireland, Chairman. Some of the compounds prepared are being investigated pharmacologically under the direction of Dr. A. S. Loevenhart of the Department of Pharmacology of the University of Wisconsin. ' "Realenzyklopaedie fur Pharmazie," vol. VII, p. 100. -- 4 Paolini, Gazz. chim. ital., 51, II, 188 (1921); C. A., 16, 557 (1922) May, 1923 MERCURY DERIVATIVES OF SAUCYI,AIJ>HYDS 1331 reaction mixture. Since phenol can be changed to monomercurated products by adding mercuric acetate to an excess of phenol without a solvent 5 it seemed likely that salicylaldehyde might be mercurated in the same way. Such, however, was found not to be the case. The failure is apparently due to the fact that the mercuration products of salicylaldehyde are insoluble in an excess of the parent substance, while those of phenol are soluble in the excess of phenol. In order to obtain a monomercurated aldehyde easily, the mononitro- salicylaldehydes are used. Mercuration by mercuric acetate in alcohol readily gives 3-acetoxymercuri-5-nitro-salicylaldehyde and 5-acetoxy- mercuri-3-nitro-salicylaldehyde. The corresponding chloromercuri com- pounds are prepared in the usual way. The mercurated salicylaldehydes dissolve in aqueous alkali. The alkaline solutions, precipitated by dil. hydrochloric acid, give the chloro- mercuri compounds. The alkali salts in the case of the nitro compounds can be recrystallized from hot water. They are highly colored, indicating a quinoid-acinitro structure. 6 The mercurated salicylaldehydes condense with primary aromatic amines forming colored Schiff's bases. Diacetoxymercuri-salicylaldehyde has been condensed in this way with aniline, ^-toluidine, ^-aminobenzoic acid and anthranilic acid. The mercurated nitro-salicylaldehydes, both acetates and chlorides, have been condensed with these amines. In the case of the acetoxymercuri compounds, one molecule of acetic acid is lost. Since this loss occurs only with the nitro compounds the products are probably anhydrides or inner salts formed between the acinitro and hy- droxymercuri groups. 4 Thus the product of the condensation of 3-acetoxy- mercuri-5-nitro-salicylaldehyde with aniline would be as follows. O Hg Yl =N-0 O=N- The corresponding chloromercuri compound condenses with amines with- out anhydride formation. As would be expected the products are less highly colored than the anhydrides. The mercurated salicylaldehydes react with hydroxylamine and with phenylhydrazine, giving metallic mercury. The Perkin reaction with acetic anhydride and sodium acetate gives tarry products from which no pure substance has been obtained. With potassium iodide the mercurated salicylaldehydes behave like 6 THIS JOURNAL, 43, 622 (1921). 6 Compare the work of Hantzsch and Auld on the mercurated nitrophenols. Ber., 39, 1117 (1906). 1332 FRANK C. WHITMORK AND EDMUND B. MIDDIvETON Vol. 45 the mercurated phenols, losing mercury with the formation of the un- mercurated aldehydes, potassium mercuric iodide and potassium hydroxide. The instability of the C-Hg linkage in these compounds is due to the presence of the phenolic hydroxyl. When the latter is protected by acetyl, methyl or ethyl, the decomposition by iodides follows a different course. The properties and reactions of such derivatives of the mercurated salicylaldehydes are being studied by one of us (M.). Experimental Part 3,5-Diacetoxymercuri-salicylaldehyde. Ten g. of salicylaldehyde and 52 g. of mercuric acetate (2 molecular proportions) are dissolved in 500 cc. of 50% alcohol con- taining 5 cc. of acetic acid. After the mixture has been heated for 1 hour on the steam- bath it is cooled and filtered. The crude diacetate obtained weighs 32 g. On standing overnight 10 g. more separates. Addition of sodium chloride solution to the filtrate precipitates 8 g. of crude dichloromercuri-salicylaldehyde. The diacetate is insoluble in all ordinary organic solvents except glacial acetic acid in which it is soluble in the pro- portions of about 1 : 5 in the boiling solution and 1 : 10 in the cold. It separates in needles which melt with decomposition at 234 (uncorr.). The crude material melts with de- composition at about 225 . 7 It is soluble in aqueous sodium hydroxide. Boiling with alcoholic potassium iodide removes all the mercury as potassium mercuric iodide forming salicylaldehyde and potassium hydroxide. The diacetate reacts with hydroxylamine and with phenylhydrazine as an oxidizing agent, forming metallic mercury. Analyses.* Calc. for CiiH 10 O 6 Hg2: Hg, 62.8. Found: Hg, 6.24, 62.8. The dichloromercuri compound is insoluble in organic solvents and does not melt at 270. Analysis. Calc. for C 7 H 4 O2Cl 2 Hg 2 : Hg, 67.7. Found: 67:8. 3(?)-Chloromercuri-salicylaldehyde. Attempts to make this substance by mer- curation of an excess of salicylaldehyde without a solvent failed, apparently because of the insolubility of the mercurated products in the salicylaldehyde. Ten g. of salicylaldehyde in 2 liters of water is treated with 26 g. of mercuric acetate (1 molecular proportion) and the mixture is stirred mechanically. As soon as the solution no longer gives a test for inorganic mercury with sodium hydroxide it is filtered. Three g. of the diacetate is thus obtained. Addition of sodium chloride solution to the filtrate gives 19 g. of a mix- ture of mono- and dichloromercuri compounds. Repeated extractions with boiling alco- hol remove 5 g. of a pure monochloromercuri-salicylaldehyde; m. p., 189-190. Sus- pended in chloroform and treated with 1 molecular proportion of iodine it gives an iodo-salicylaldehyde; m. p., 52-58. This is apparently the 3-iodo-salicylaldehyde which is reported to melt at 55. The residue insoluble in hot alcohol appeared by anal- ysis to be a mixture of dichloromercuri- and monochloromercuri-salicylaldehydes. The latter is probably the 5-chloromercuri compound. No method of separating this mixture has been found. Analysis. Calc. for Cr^O^ClHg: Hg, 56.3. Found: 56.4. Nitration of Salicylaldehyde. 9 3-Nitro- and 5-nitro-salicylaldehydes were pre- pared according to the method described by Miller. 3-Acetoxymercuri-5-nitro-salicylaldehyde. Twelve g. of 5-mtro-salicylaldehyde and 23 g. of mercuric acetate dissolved in 400 cc. of alcohol containing 5 cc. of acetic acid are heated 1 hour on the steam-bath. The precipitate is filtered, washed and dried; 7 Henry and Sharp give the melting point as 133. 8 For method of analysis see note, THIS JOURNAL, 44, 1548 (1922). 9 Miller, Ber., 20, 1928 (1887). May, 1923 MERCURY DERIVATIVES OF SAUCYLAU>EHYDES 1333 yield, 26 g. It is crystallized from glacial acetic acid, the only organic solvent in which it is appreciably soluble.' It forms pale yellow crystals which do not melt at 260. It dissolves in aqueous sodium hydroxide to give a yellow solution. Analyses. Calc. for C 9 H 7 O 6 NHg: Hg, 47.1. Found: 47.1, 47.1. 5-Acetoxymercuri-3-nitro-salicylaldehyde. Four g. of 3-nitro-salicylaldehyde and 7 g. of mercuric acetate are treated as described above. The product weighs 9 g. It is recrystallized from glacial acetic acid. It does not melt at 260. Analysis. Calc. for C 9 H 7 O 6 NHg: Hg, 47.1. Found: 46.9. 3-Chloromercuri-5-nitro-salicylaldehyde. Ten g. of the corresponding acetate dissolved in dil. sodium hydroxide solution and acidified with dil. hydrochloric acid pre- cipitates 8 g. of the chloride. The substance is insoluble in organic solvents and does not melt at 260. Analyses. Calc. for C 7 H 4 O 4 NClHg: Hg, 49.9. Found: 49.1, 49.3. Condensation of Mercurated Salicylaldehydes with Aromatic Amines Schiff's bases are obtained by heating the mercurated salicylaldehydes with an ex- cess of aniline or />-toluidine. Similar compounds are obtained from the aminobenzoic acids by refluxing the latter in alcohol. Less pure products can be obtained by refluxing the aldehydes with the aminobenzoic acids in acetic acid. 3,5-Diacetoxymercuri-salicylal-aniline. Five g. of the mercurated aldehyde dis- solved in 10 cc. of hot aniline and cooled gives 5.5 g. of a brick-red amorphous product which is insoluble in organic solvents and does not melt at 260. The crude product is washed thoroughly with benzene and dried at 100 for analysis. Analyses. Calc. for Ci7Hi5O 6 NHg2 : Hg, 56.2. Found: 56.2, 56.8. 3,5-Diacetoxymercuri-salicylal-p-toluidine. The preparation and properties of this substance are similar to those of the aniline compound. Analyses. Calc. for Ci 8 H 17 O 6 NHg: Hg, 55.1. Found: 54.6, 54.9. 3,5-Diacetoxymercuri-sah'cylal-^-ammobenzoic Acid. Five g. of the aldehyde yields 5.5 g. of a deep red, insoluble powder which does not melt at 250. Analysis. Calc. for C 18 H 15 O 7 NHg 2 : Hg, 52.9. Found: 53.0. The substance is soluble in dil. alkali. Precipitation by acetic acid gives a product richer in mercury (56.7% ) . This may consist of anhydride or a partly hydrolyzed product in which one of the acetoxymercuri groups has been changed to an hydroxymercuri group. 10 3,5-Diacetoxymercuri-salicylal-anthranilic Acid. The preparation and properties of this substance are similar to those of the ^-aminobenzoic acid compound. Analysis. Calc. for C ]8 Hi 5 O 7 NHg 2 : Hg, 52.9. Found: 52.3. 3(?)-Chloromercuri-salicylal-aniline. Two g. of the alcohol-soluble monochloro- mercuri-salicylaldehyde dissolved in 4 g. of hot aniline gives on cooling 2 g. of flat, yellow plates which are insoluble in organic solvents; m. p., 182-184. Analysis. Calc. for Ci 3 Hi ONClHg : Hg, 46.4. Found: 46.5. Anhydride of 3-Hydroxymercuri-5-nitrosalicylal-aniline. Five g. of 3-acetoxy- mercuri-5-nitro-salicylaldehyde dissolved in 8 cc. of hot aniline and cooled gives a deep red amorphous product which is insoluble in organic solvents but is soluble in alkali. It does not melt at 250. Analyses show that 1 molecule of acetic acid has been lost during the condensation or during the drying of the product. This probably takes place between the acinitro and acetoxymercuri groups. 6 Analyses. Calc. for Ci 3 H 8 O 3 N 2 Hg: Hg, 45.5; C, 35.4. Found: Hg, 45.6; C, 35.0. 1 White, THIS JOURNAL, 42, 2363 (1920). 1334 FRANK C. WHITMORE AND EDMUND B. MIDDLETON Vol. 45 A similar product is formed from aniline and 5-acetoxymercuri-3-nitro-salicylalde- hyde. 3-Chloromercuri-5-nitrosalicylal-anilme. Three g. of the aldehyde dissolved in 8 cc. of hot aniline and cooled gives an orange-red product which is insoluble and does not melt. Analyses. Calc. for Ci 3 H 9 O 3 N 2 ClHg: Hg, 42.1. Found: 42.5, 42.8. Summary 1. Mercuration of salicylaldehyde by mercuric acetate gives mainly a dimercurated product with only small amounts of a monomercurated aldehyde. 2. The two nitro-salicylaldehydes give normal mercuration products. 3. The mercurated salicylaldehydes lose all their mercury when treated with potassium iodide, hydroxylamine or phenylhydrazine. 4. The mercurated salicylaldehydes form Schiff s bases with aromatic amines. EVANSTON, ILLINOIS Gaylord Bros. Makers Stockton, Calif. PAT. JAN. 21, 1908 60SG03 UNIVERSITY OF CALIFORNIA LIBRARY