166 PYMAN META-SUBSTITUTED X1X.-Metu-substituted Aromatic Compounds. By FRANK LEE PYMAN. AT the suggestion of Dr. Charles Walker of Sd eizium Glasg ow at tempts were made in 1913 to form the selenium analogue of arsanilic acid, namely p-aminophenylselenic acid NH,*C,H,*Se03H in order to determine its physiological action. Whilst? aniline sulphate and arsenate readily yield sulphanilic acid and arsanilic acid, respectively a t an elevated temperature no similar compound could be obtained from aniline selenate. It was found however, that phenylselenious acid gave on nitration a nitrophenylseleniouj acid which is shown to be the meta-compound in the manner described below. On reducing this compound with sodium hydrogen sulphite di-maitrophenyl diselelzltde resulted and gave di-m-aminophenyl diselenide on further reduction with sodium sulphide.Di-m-aminophenyl diselenide gave on acetylation di-m-acetylaminophemyl cFiselenide from which m-acetylminophenyl-selenious acid was obtained by oxidation with nitric acid. From this the salts of m-acet ylaminophenylselenic acid were obtained on oxidation with potassium permanganate whilst on attempting to liberate the free acid hydrolysis h k place with the formation of m-amino pheny ls e 1 e lzlic acid : NO,*C,H,*SeO,H + (NO,*C,H,-Se) + (NH,*C,H,*Se) -+ (NHAc*C,H,*Se) -+ NHAc*C,H,*SeO,H -+ NHAc*C,H,*SeO,K + NH,*C,H,*SeO,H. When these results were first communicated to the Society (P., 1914 30 302) the orientation of the nitro-group in nitrophenyl-selenious acid had not been determined and in the discussion on the paper Dr.Tuck suggested that the constitution of this acid might be settled by preparing the three isomerides by the acttio AROMATIC SELENIUM COMPOUNDS. 16’7 of the nitrobenzenediazoniu chlorides on potassium selenocyanate and suitable after-treatment. This method had already been applied by Bauer (Ber. 1913 46 92) to the preparation of o-nittro-phenyl selenocyanate and by Morgan and Elliot (P. 1914 30, 248) to the preparation of p-chloi-ophenyl selenmyanate and their derivatives. At the author’s request Mr. H. King has now kindly prepared 712-nitrophenyl selenocyanate from which he has obtained on r e duction with tin and hydrochloric acid di-m-aminophanyl diselenide identical with the product resulting from the reduction of nitrophenylselenious acid thereby proving the constitutdon of the compounds described above.EXPEILIMENTAL. Pheitylseleniws Acid PhSe0,H. The preparation of this acid and its nitrate have been described by Stoecker and Krafft (Bey. 1906 39 2197). Diphenyl diselenide (1 part by weight) was dissolved in concentrated nitric acid (40 parts by weight) and heated. On cooling the well-crystallised nitrate of phenylselenious acid separated. In order to liberab the free acid the nitrate was dissolved in ammonia and mixed with silver nitrate when silver phenylselenite was precipitabed and gave the free acid when decomposed with the equivalent quantity of hydrochloric acid. Doughty (Amer. Chem. J. 1909 41 326) subsequently obtained this acid by the action of hydrochloric acid on phenylselenic acid resulting from the interaction of selenic acid and benzene.He was unable to confirm the previous author’s statement that the acid crystallised with 2H20 finding it t a be anhydrous. For t’he purpose of the present investigation considerable quanti-ties of this acid wete required gnd a modification of Stoecker and Kraff t’s process was adopted. Instead of employing pure diphenyl diselenide the mixture of this substance with selenophenol, obtained by the action of selenium on magnesium phenyl bromide (Taboury Bull. Soc. chinz. 1903 [iii] 29 761) was used. On treating this with 4 c.c.-instead of 30 c.c.-of nitric acid for each gram phenylselenious acid nitrate was readily prepared in quantity. When mixed with sufficient ammonia to neutralise the nitric acid it gave free phenylselenious acid which was found to be practically anhydrous in agreement with Doughty’s observation.To a solution of magnesium phenyl bromide in dry ether pre-pared from 24 grams of magnesium and 157 grams of bromo-1 168 PYMAX META-SUBSTITUTED benzene 79 grams of selenium were added gradually and the mix-ture was boiled for half an hour. The product was decomposed with ice and dilute hydrochloric acid well shaken and the ethereal layer removed the aqueoys layer being extracted with ether twice again The ethereal extracts were colmbined dried with calcium chloride and the solvent was removed on the water-bath. The resulting oil (about 130 grams) was then allowed to flow drop by drop into concentrated nitric acid (D 1.4) of which 4 C.C.were employed for each gram of the oil. The nitric acid solution was then digested for an hour on the water-bath and kept when crude phenylselenious acid nitrate separated in hard crystals. This was collected on asbestos dissolved in water and the solution filtered from insoluble mattes. The solution was then extracted with ether to remove further impurities and evaporated to a syrup. On cooling this set to a chalky mass of the nearly pure nitrate which, after t'horough drying in the air amounted to about 110 grams. The yield is thus 44 per cent of the theoretical. For the preparation of the free acid 10 grams of the nitrate were dissolved i n 20 C.C. of water and 6 C.C. of 10 per cent. aqueous ammonium hydroxide added.On stirring phenylselenious acid separated in sandy yellow grains which were purified by crystallisation from water. 6.5 Grams of the pure acid were isolated without carrying out the separation t o an end whilst 7.6 grams are required theoretically. Phenylselenious acid pre-pared in this way melted a t 124-125O (corr.) after drying a t looo. The air-dried acid was practically anhydrous. (Found loss at 100°=0.4; C=37*6; H=3*3. C,H,-SeO,H requires C=38*0; H=3*2 per cent.) Sodium phenylselenite crystallises from water in colourless plates containing 2H,O. It is readily soluble in water. Found loss a t looo 14.6. Found in anhydrous salt Se= 37.9 37.5." C6H,-Se0,Na,2H,0 (247.2) requires H,O = 14.6 per cent. C,H,*bO,Na requires Se = 37.5 per cent. Salts of Phenylselenic Acid.Stoecker and Krafft (loc. cit.) prepared phenylselenic acid by the oxidation of diphenyl diselenide with moist chlorine Doughty by the method given above (Zoc. cit.). The potassium salt can be obtained conveniently by oxidising phenylselenious acid with * For uls estimation of selenium in the compounds described in this paper Fmrichs'a method (Arch. Pharm. 1902 M 666) was employed AROMATIC SELBNiWM COMPOl?lKDS. 169 potassium permanganate removing -manganese dioxide and evaporating t o low bulk when it ci-ystallises from the solution. Potassium phenylselenaate forms colourless prismatic needles which after being dried in the air sinter from about 50" and melt from 65O to 90° in the water of crystallisation. It is readily soluble in cold and very readily so in hot water.Found loss in a vacuum over H,SO and then a t looo 12.7. C,H,-Se03K,2H,0 (279.4) requires E,O = 12.9 per cent. Found in anhydrous salt Se = 32 * 2. C,H,*SeO,K requires Se = 32-6 per cent. Sodiunz phenylselenat e was prepared from the barium salt which has been described by Doughty (Zoc. cit.) by double decomposition with sodium sulphate. It crystallises from water in long clear, oblong plates which contain 3H20 and is readily soluble in cold, very readily so in hot water. Found in air-dried salt loss at 120°=24.2; Se=26*5. C,H,-Se03Na,4H,0 (299.2) requires H,O = 24.1 ; Se= 26.5 per cent. Jn-Nitl.ophenylselertioiis Acid NO,*Cf,H,*SeO,H. Phenylselenious acid did not yield a nitra-derivative when treated with a mixture of sulphuric and nitric acids a t looo.When subjected to the action of a large excess of fuming nitric acid a t 150° for one hour it gave a 20 per cent. yield of m-nitrophenyl-selenious acid. The best method for the preparation of this acid, hawever was found in the action of nascent nitric acid generated from potassium nitrate. Thirty grams of phenylselenious acid nitrate were dissolved in 30 C.C. of sulphuric acid and the solution was cooled with running water. Twelve grams of finely powdered potassium nitrate were then stirred into the solution which was similarly cooled. The mixture was heated for two hours in the steam-bath and poured into 600 C.C. of water. After keeping for several hours the separated crystals were collected. They amounted tc 17.4 to 18.7 grams of an almost pure product melting a t 155O or slightly lower.~-~itrophenylseZenicrus acid crystallises from wahr in . yellow, prismatic needles which melt a t 156-157O (corr.) after drying a t looo. It is fairly readily soluble in boiling water sparingly so in cold. Found loss a t l0Oo=0*4 ; in dried substance C= 30.8 ; H = 2.2. CGH,O,NSe (234.2) requires C = 30.8 ; H = 2.2 per cent f 70 FYMAN META-SUBSTITUTED m-Nit r o p k en y lselenic A cid NO,* C,H,* Se0,IT. Thirty-five grams of m-nitrophenylselenious acid were dissolved in 600 C.C. of boiling water t o which 20 C.C. of 10 per cent. aqueous potassium hydroxide had been added and mixed with a solution of 16 grams of potassium permanganate in 200 C.C. of hot water. Further small quantities of permanganate were then added until the red colour no longer' quickly vanished.The manganese dioxide was removed by filtration and the solution evaporated to low bulk and cooled when potassium m-nitrophenylselenate crystallised out. After purification by recrystallisation from water 34 grams were obtained. Pofnssium m-nitroph enylselennt e forms hard yellow rosettes of flat needles. It is anhydrous and is readily soluble in hot. but somewhat sparingly so in cold water. It explodes violently a t about 330° (corr.). Found Se - 27.1. C,H,O,NESe (288.3) requires Sc = 27.5 per cent. Bnrizrm m-nitrophenylseltwnte was prepared from the potassium salt by double decomposition with the calculated quantity of barium chloride. It forms colourless leaflets which are fairly readily soluble in hot but sparingly so in cold water.It contains 2H20 which are lost a t 120° but not a t 1 1 0 O . Found in air-dried salt loss a t 120O = 5.6. Ba = 20.2. C,,H80,,N,BaSe,,2H,0 (671.9) requires H,O =5*4 ; Ba = 20.5 per cent. m-Nitrophen?/7se2e?2ic acid was prepared from the barium salt' by the addition of the calculated quantity of sulphuric acid, removal of barium sulphate and evaporation t o a syrup when it cryshllised on keeping in colourless plates containing 2H20. The air-dried acid melts below looo but after drying first in a vacuum over sulphuric acid then att looo it is rendered anhydrous and then melts a t 1 4 6 O (corr.). Found Ioss a t 100°=12*8. 0-2379 dried a t looo required 18.95 C.C. of NI20-NaOH for neutralisation whence equivalent = 251.C,H,0,NSe,2H20 (286.3) requires H,O = 12.7 per cent. C6H,05NS0 requires M.W. = 250.3. Di-rn-nit rophenyl Diselenide (NO,*C,H,*Se),. Twenty-f our grams of m-nitrophenylselenious acid were dissolved in 250 C.C. of boiling water and a saturated solution of sodiu AROMATIC SELENIUM COMPOUNDS. 171 hydrogen sulphite was added so long as a turbidity was produced. After cooling and stirring the oil which had separated became crystalline and was collected and washed with water. The theoretical yield-20.5 grams-was obtained and the product melted a t 79O. After crystallisation from ether this compound formed yellow spears which melted a t 83O (corr.). Found C=35*6; H=2.2. Cl,H80,N,Se2 (402.5) requires C = 35.8 ; H = 2.0 per cent. It is insoluble in water moderately readily soluble in cold alcohol or ether fairly readily so in hot alcohol and easily so in hot ether.I)i-m-aminophen(yI Diselenide (NH2*C,H,-Se),. Fifty grams of di-m-nitrophenyl diselenide were added to a solu-tion of 300 grams of commercial hydrated sodium sulphide in 500 C.C. of 10 per cent!. aqueous sodium hydroxide previously heated to about 60° and the mixture was boiled for one hour under a reflux condenser. One litre of boiling water was then added and an excess of concentrated hydrochloric acid. After digestion for two hours on the steam-bath the separated sulphur was removed by filtration. The filtrate was cooled basified with sodium carbonate and extracted with ether. The ethereal solu-tion was dried with anhydrous potassium carbonate and distilled.The residue was mixed with an excess of 10 per cent. hydrochloric acid when 39.7 grams of di-m-aminophenyl diselenide dihydro-chloride separated in sandy crystals. Di-m-amin o ph enyl disetenide dih y droc hl oride cry st?llises from dilute hydrochloric acid in yellow grains formed of small needles. It melts and decomposes a t 291-292O (corr.). It is readily soluble in hot but sparingly so in cold dilute hydrochloric acid. Found loss a t P O O o = l . l ; in dried salt C=35*3; €€=3*5; Se =37-5 ; C1= 16.8. CI2Hl2N2Se2,2HC1 (415.4) requires C = 34.7 ; H = 3.4 ; Se = 38.1 ; C1=17.1 per cent. Di-m-acet?/laminoyhen?/l Diselenide (CH,*CO*NH*C,H,*Se),. 25.2 Grams of di-m-aminophenyl diselenide dihydrochloride were converted into the base and this was treated with 25 O.C.of acetic anhydride. The clear liquid quickly began to crystallise and soon set to a yellow chalky-mass which was washed well with ether and dried in the air. 19-6 Grams of di-m-acetylaminophenyl diselenid melting a t 180° were thus obtained the yield amounting to 76 p r ce& of the theoretical. For the preparation of this substitnce the previous iaolation of di-m-aminophenyl diselenide as the dihydrochlmide is unnecessary ; thus 91 grams of dim-nitrophenyl diselenide were reduced by the method given previously and the ethereal residue of crude di-m-aminolphenyl diselenide was mixed with 50 C.C. of acetio anhydride and treated as above. The resultJng di-m-acetylaminophenyl diselenide melted a t 179* and amounted t o 76 grams that is 79 per cent.of khe theoretical. Di-mace tylaminophenyl diselenide crystallises from glacial acetic acid in rwettes of short yellow needles which melt a t 185-186O (corr.). It is anhydrous and is insoluble in hot or cold water, almost insoluble in hot or cold ether readily soiluble in hotl alcohol or glacial acetic acid but sparingly so in these solvents when cold. Cl,R,,0,N2Se (426.6) requires C= 45.0 ; H == 3-8 per cent. Found C=45*0; H=4.0. Formcctiom of Di-m-aminopheizyl niselenide b y the Rechiction of rn-Nitrophen y l Sele nocyana t e . m-Nitroaniline (6.9 grams) was diazotised in dilute hydrochloric acid solution a t Oo and after filtering from 1 gram of diazoamino-compound the acidity of the solution to Congo paper was removed by the addition of 10 grams of sodium acetate crystals.Potassium selenocyanate (7.2 grams) dissolved in a little water was added slowly with stirring. There was a brisk evolution of nitrogen accompanied by the separation of a red oil. On washing with water the latter gradually solidified and was dissolved in ether to free it from selenium powder (0.6 gram). The ethereal solution was conmntrated again filt'ered from a small quantity of a viscous red air and finally evaporated t o a syrup which crystallised on stirring. The product consisted of transparent crystals embedded in a small quantity of a deep red gum. The yield of crude m-nitrophenyl selenocyanate was 7.2 grams or 73 per cent. of theory. The crude product (3.4 grams) was dissolved in hot alcohol (50 c.c.) and reduced by boiling for one hour with tin (3.5 grams) and hydrochloric acid (45 c.c.; 32 per cent.).On conmntration under diminished pressure the hot solution deposited an orange yellow granular crystalline stannichloride (5.8 grams). One gram of the stannichloride was dissolved in water and the tin removed as sulphide. The solution on concentration gave tw AROMATIC SELENIUM COMPOUNDS. 173 successive separations of crystalline di-m-aminophenyl diselenide dihydrochloride 0.2 gram and 0.25 gram each melting a t 278-280° (uncorr.). (Found C1= 17.0. Calc. C1= 17.1 per cent .) Di-m-aminophenyl diselenide dihydrochloride obtained by the reduction of di-m-nitrophenyl diselenide melted a t the same temperature as did a mixture of the two. Moreover both form a sparingly soluble primrose-yellow stannochloride crystallising in microscopic needles and a stannichloride which tends to separate as an oil from cold solutions but in granular crystals from hot Solutions.Acetylation of the di-m-aminophenyl diselenide prepared from m-nitrophenyl selenocyanate gave di-nz-acetylaminophenyl di-selenide in short needles which melted a t 183-185O (uncorr.) the acetyl derivative of the reduction productl of di-m-nitrophenyl diselenide melting a t the same temperature whilst a mixture of the two showed no depression of the melting point. m- A ce tyZamimoph.ertyZseE e nious A cid CH,*CO*NH*C,H,* Se0,H. Ten grams of di-m-acetylaminophenyl diselenide were added with stirring in quantities of about 1 gram to 40 C.C. of nitric acid (D 1.4) kept a t - 6 O to -3O.A t first the diselenide dissolved, giving a clear solution but the separation of white crystals soon commenced and increased on the further addition of this substance. The crystals were collected on asbestos washed with concentrated nitric acid and drained on porous porcelain. This substance melted a t 146O and was the nitrate of m-acetylaminophenylselenious acid. After grinding it1 with water filtering and washing with water crude m-acetylaminophenylselenious acid melting a t 201°, remained undissolved. The product a t this stage still contained nitric acid and a portion on boiling with water with the view of recrystallising it readily oixidised. The whole was therefore dis-solved in an excess of hot dilute ammonia (200 c.~.) treated with animal charcoal filtered and acidified with glacial acetic acid.On keeping m-acetylaminophenylselenious acid crystiallised in fine, colourless needles which were collected washed well with water, and dried in the air. The yield amounted to 8.5 grams of the pure acid. in-A ce tytamiizophen ylselert ious acid crystallises from boiling water in short slender colourless needles which begin to turn brown at about ZOOo and melt and decompose a t 209O (corr.). It is sparingly soluble in hot very sparingly so in cold water. Found C=39.5 39.5; H=3.7 3.8. C8H,0,NSe (246.3) requires C = 39.0 ; H = 3.7 per cent. I 174 META-SUBSTITUTED AROMATIC SELENIUM COMPOUKDS. Sodium m-acet ylaminophen ylselenit e crystallises from water in After drying in the air this salt contains It microscopic needles.7H,O of which 4 are lost a t looo and the remainder a t 120O. is fairly readily soluble in cold and easily so in hot water. Found loss a t looo= 18.2 ; loss a t 120"=32-2. CsHSO3NNaSe,7H2O (394.4) requires 4H,O = 18.3 ; 713,O = 32.0 per cent. Salts of m-A cetylaminophe~~lsele~~c Acid, CH,-CO NH=C,H,*SeO,H. Fifty-five grams of m-acetylarninophenylselenious acid were dis-solved in 70 c . ~ . of 10 per cent. ammonia and a litre of hot' water, and mixed with a hot aqueous solution of 26 grams of potassium permanganate. After digestion for a few minutes on the water-bath the slight excess of permanganate was reduced by means of alcohol. The solution was boiled filtered from manganese hydr-oxide and 28.5 grams of barium nitrate were dissolved in it.On evaporating t o a small volume and keeping barium m-acetylamino-pheiiylselenate crystallised out. After recrystallisation from water, 48 grams of the pure salt were obtained. A considerable further quantity was subsequently isolated from the mother liquors. Barium m-acetylaminophenylselenate crystallises from water in hard colourless flat needles containing 4H,O. It is fairly readily soluble in cold very readily so in hot water. Found loss a t 120°=10.1. Found in dried salt Ba=20-8. Sodium m-acet~lamin~phe?~~lse~en~t e was prepared f r am the barium salt by double decomposition with sodium sulphate. It, crystallises from water in colourless woolly needles and from alcohol in prismatic needles in both cases without solvent of crystallisation.It is very readily soluble in water sparingly so in cold alcohol but faJrly readily so in hotl alcohol. @,,H,,0,N2BaSe,,4H,0 (732.0) requires H,O = 9.8 per cent. C,,HIGO,N,BaSe requires Ba = 20.8 per cent. Found Se = 27.9. C,H,O,NNaSe (284.2) requires Se = 27.9 per cent. m-*4 minophenylselenic A cid NH,*C,H,=SeO,H. Forty-five grams of barium m-acetylaminophenylselenate were dissolved in 500 C.C. of boiling water and sufficient sulphuric aci THE N-BUTYLARYLAMJNES. PART 111. 176 was added exactly t o remove the barium. The solution was then boiled filtered from barium sulphate and evaporated to a m a l l volume under diminished pressure when 13 grams of m-amino-phenylselenic acid crystallised from the solution. m-A minophemylseleltic acid crystallises from water in colourless needles which contain 2H,O and after drying a t looo melts and decomposes a t 229O (corr.). It is readily soluble in hot sparingly so in cold water. Found in air-dried substance loss a t looo= 11.4. Found in dried substance C = 32.7 ; H = 3.3. Sodium m-anainlo(plteltylselenate crystallises f rom water in plates, Found in air-dried salt loss atl 120°=19.9. Found in dried salt Se=33-0. TEE WELLCOME CHEMICAL WORKS, C6H70,NSe,l l-H,O requires E20 = 10.9 per cent. CGH70,NSe (220.3) requires c = 32.7 ; €1 = 3.2 per cent. which are readily soluble in cold water. CGH60,"aSe,3$H,0 requires H,O = 20.6 per cent. C,H6O3"aSe (242.2) requires se= 32.7 per cent. DARTFORD KENT. [Received February 4th 19 19.