FORSTER : CAMPHOROXIME. PART 111. 1141 By MARTIN ONSLOW FORSTER, Ph.D., D.Sc. ON the failure of an nttenipt to prepare a-bromocamphoroxime by the direct action of bromine on camphoroxime dissolved in glacial acetic acid (Trans., 1897, 71, 1030), I was led to study the behaviour of the oxime towards an alkaline solution of potassium hypobromite. When treated with this agent, cnmphoroxime undergoes simultaneous bromination and osidation, a quantitative yield of the compound, C,oH,,BrNO,, being readily obtained if certain conditions are observed. The change is expressed by the equation Cl0Hl7NO + 2KOEr = C,oHl,BrNO, + KOH + KBr. The new derivative is not an oxime, being indifferent towards benzoic chloride, but it contains a nitroso-group, produced by removal of hydro- gen from the oximido-residue.It is remarkably indifferent towards aqueous potash, from which i t may be distilled without undergoing apparent change, mhilst hot concentrated nitric acid scarcely dissolves it, and, at first, has no perceptible action on it, On dissolving the bromonitroso-derivative in concentrated sulphuric acid, the elements of water are withdrawn, and the compound C,,H,,BrNO, is produced. Unlike the substance from which it is obtained, this compound does not give Liebermann’s reaction for nitroso- derivatives ; moreover, cold concentrated nitric acid dissolves it im- mediately, whilst hot hydrochloric acid transforms it into an isomeride which yields a benzoyl derivative by the Schotten-Baumann method. These isomeric substances are opticslly inactive, although the initial compound is strongly lsvorotatory.Under the inhence of hot caustic alkalis, the isomerides, CloH,,BrNO, break up in a remarkable manner, yielding a nitrile of the empirical1142 FORSTER : CAMPHOROXIME. PART III. BEHAVIOUR OF formula C,H,,N. The production of such a compound involves elimina- tion of carbon monoxide and hydrogen bromide in accordance with the equation, C,,,H,,BrNO = C,H,,N + CO + HBr. The nitrile, when hydrolysed with alcoholic potash, yields the corre- spoilding a u d e , which has the formula C,H,,NO, and is therefore isomeric with the amides of isolauronolic and caniphoceenic acids ; these, however., melt a t 129-130' (G. Blanc, Compt. Teizd., 1896, 123, 749) and 155' (Jagelki, BET., 1899, 32, 1506) respectively, whereas the new smide melts at 90'.Nevertheless, its relation to isolauronol- amide must of necessity be a close one, because hydrochloric acid con- verts it into that substance along with isolauronolic acid. It has been shown that when sodium orthoethylic camphorate is submitted to electrolysis, the ethylic salt of campholytic acid is formed (Walker, Trans., 1S93,63, 495) ; the acid itself is also obtained by the action of nitrous acid on dihydroaminocampholytic acid, produced on elimiuating carbon monoxide from P-camphoramic acid, NH,* CO*CSH,,*COOH, by the agency of sodium hypobromite (Noyes, Ber., 1895, 28, 547). Electrolysis of sodium orthoethylic camphorate also yields isolauronolic acid, first described by Walker, who then called it camphothetic acid (Zoc.cit.) ; the production of this compound from sulphocamphylic acid was recorded about a month later by Koenigs and Hoerlin (Be?*., 1893, 28, S l l ) , from whom it received its present name. These isomerides, isolauronolic and cainpholytic acids, are now re- garded as the cis- and c&rccns-modifications respectively of s single acid, mainly because both contain an unsaturated linking in the ap-position, and also on account of the readiness with which isolauronolic (cis-cam- pholytic) acid is produced from the labile isomeride. Mere contact with cold dilute sulyhuric acid at ordinary temperatures will suffice to convert the liquid campholytic acid into solid isolauronolic acid (Noyes, Ber., 1895,28,54S), and in a private communication, Professor Walker informs me that an impure specimen of campholytic acid which has remained in his possession for some years, has now become almost entirely transformed into isolnuronolic acid.CH,-CH Neither the formula (CH,),C<,(,,s):tl.,;dH' by which Blanc represents the structure of isolaurondic -acid (Bull. Soc. CIL'L~., 1898, [iii], IS, 634 ; compare also 1899, [iii], 21, 830), no19 the expression - - UH,-C*COOH (CH8)&<CH(CH,). dH adopted by W. H. Perkin, jun. (Trans., 1898, 73, 796), suggests any reason for supposing that one of the two possible structural isomerides which have the unsaturated linking in theCAMPHOHOXIME TOWARDS POTASSIUM HY POBROMITE. 114s up-position would be more stable than the other. There is consequently every justification for the accepted view of the relation between cam- pholytic and isolauronolic acids, and the readiness with which the new amide is converted into isoltluronolamide and isolauronolic acid renders it highly probable that the substance in hand is the hitherto unknown amide of campholytic acid, Up to tlie present, however, it has not been found possible to verify this anticipation experimentally, because the amide reeists the action of alcoholic potash, and the employment of an acid as hydrolytic agent is obviously precluded; it is noteworthy that isolauronolamide is described by Blanc as being very indifferent towards alcoholic potash.The passage from camphoroxime to isolauronolic acid is represented in the following scheme : Camphoroxime, C,,H,,ON, I Bromonitroso-compdund, C,,H1,O,N Br.I Isomeric compounds, CloH,,OXBr. I Ni trile, :C,H,,N. I Amide, C,H,,ON. 1 I Isolauronolamide, C,I3,,ON. I Isolauronolic acid, CoH1402. As regards the constitution of the bromonitroso-comyoiind and the isomerides obtained from it on withdrawing the elements of water, discussion at the present moment would be premature. Experiments on the behaviour of menthoneoxime, isoni trosocamphor, thymoquinone- oxime, and carvoxime towards alkaline hypobroniite have been carried out for purposes of comparison, but no useful information has been obtained as yet from these sources. It is clear, however, that the initial substance does not belong to the class which includes bromonitrosopropaue, obtained by Piloty from acetoxime and bromine in presence of pyridine (Ber., 1895, 31, 453), because it contains more oxygen than camphoroxime, whereas the conversion of acetoxime into bromonitrosopropane merely involves removal of hydrogen and addition of bromine.There is every probability that the substance is a true bromonitroso-derivative containing the complex >CBr*NO, the presence of the group, >C:NOBr being rendered highly improbable by the stability of the compoulid towards aqueous alkali. The disposition of the oxygen atom which has been added to the molecule can be ascer- tained only by further study, and the work is being continued from this point of view.1144 FORSTER : CAMPHOROXLhfE, PART 111. ffEHAVfOdB OF EXPERIMENTAL. Action of Potassium Hypobromite on C'mtphoroxintc. A solution of potassium hypobromite was first prepared by dissolving 600 grams of caustic potash in 1000 C.C.of water, cooling the solution with crushed ice, and adding 400 grams of bromine to the well-stirred liquid. 100 grams of finely-powdered camphoroxime were next converted into a thin paste with SO0 C.C. of water, and treated with 200 grams of caustic potash dissolved in 500 C.C. of water. The oxime, suspended and in part dissolved in the alkali, and cooled by fragmentsof ice, was finally mixed with the cold solution of hypo- bromite, which quickly transformed i t into n pale green solid having a faint, pungent odour. After 24 hours, the product had risen to the surface in a compact mass, and the clear liquid was therefore removed with the aid of a syphon ; the green solid was washed several times with water, and finally spread in thin layers on blotting paper. On exposure to air, the substance became pale yellow, but retained its pungent odour.The yield approached that required by theory. When crgstallised twice from hot alcohol, the compound mas obtained in snow-white, fern-like aggregates, and melted at 220°, forming a colourless liquid which imiueditltely began to turn red and evolve gas. The substance could not be powdered, because moderate pi'essure trans- forms it into tough, camphor-like masses; it was therefore cut- into small fragments for analysis and dried at 80". 0.2708 gave 0.4570 CO, and 0.1503 H,O. 0.4048 ,, 19.8 C.C. moist nitrogen at 23' and 769 mm. N = 5.57. 0.2376 ,, 0.1693 AgBr. Br=30*32, CloH,,O,NBr requires C = 45.80 ; H = 6-10 ; N = 5.35 ; Br = 30.53 per cent, The new derivative from camphoroxime gives Liebermann's reaction €or nitroso-compounds, It distils readily in an atmosphere of steam and is exceesively soluble in benzene or petroleum.Concentrated nitric acid has no action on the substance, which merely fuses t o a yellow oil when heated with it, and resolidifies on cooling; it is also indifferent towards boiling aqueous potash, from which it may be dis- tilled without undergoing any apparent change. A solution containing 0.34'75 gram dissolved in 25 C.C. of absolute alcohol at 23' gave uD -1" 5' in a 2-dcm. tube, whence [aID -54.7'. A solution of 0,5061 gram in 25 C.C. of benzene at 21' gave aD - 2" 39.5' in the same tube, corresponding to [a], - 65.6'. A determination of the molecular weight in benzene solution gave the following result : C = 46.02 ; H = 6.16.CAMPHOHOXIME TOWARDS POTASSIUM HYPOBROMITE.1145 Grams of Granls of benzene. suJ>stmcc. Depression of Molecular weight Grams of substRllce 'I' 'O') SOlVCll P'''s t. Of frceziiig point. deduced. 16'66 9 ) 9 9 0.292" 0'428 0.539 0.3312 1.3875 0 -3352 2.0120 0.4372 2'6242 282.8 230.3 238.5 Reduction qf the B r o n i o ~ ~ i t r 0 ~ 0 - ~ 0 ~ ~ ~ ~ ~ 0 ~ n ~ 2 . - - 5 grams wore dis- solved in glacial acetic acid and treated with 5 grams of zinc dust while the liquid was cooled with ice. On diluting the filtered solution with water, a pale yellow oil separated, and aftor several days, colourless crystals were deposited. The oil had the odour of campholenonitrile, which is generally produced when camphoroxime is heated with glacial acetic acid and zinc dust.The solid substance was dissolved in hot petroleum, which deposited the characteristic crystals of camphorouime, melting at 118'; a 3.2 per cent. solution in absolute alcohol gave [.ID - 41 *lo. Action of Concentrated ~SuZphzt~ic Acid on the 131-onionitroso-compound. A beaker coiitaiiiilig 800 C.C. of concentrated sulphuric acid was surrounded with a freezing mixture. When the temperature of the acid had fallen below Oo, the bromonitroso-compound was added i n small quantities a t a, time; meanwhile the liquid was well stirred and maintained at n temperature below 10'. A n orange coloration was developed on first adding the substance, but the liquid rapidly became dark brown, and a highly scented, viscous oil rose t o the surface.When 100 grains of material had been added, the oil was removed, and the acid allowed to flow in a thin stream on to finely crushed ice, which precipitated a pale yellow solid. The latter was collected, mashed, spread on porous earthenware, and dissolved in the minimum quantity of boiling alcohol, which was then rapidly cooled. The yield mas disappointing, as operations involving 200 grams of the bromonitroso-compound have never f urnishecl more than 75 grams of the crystallised product, and on one occasion only 50 grams were obtained ; the theoretical amount, allowing for the production of the fragrant oil, is 170 grams. I n order to secure a comparatively good yield, it is absolutely essential to maintain the sulphuric acid in con- stant agitation while the bromonitroso-compound is being added ; the latter rises t o .the surface of the acid if this remains undisturbed, where it becomes heated, and blackens, evolving gas.Even when1146 FORSTER : CAMPHOROXIME. PART 111. BEHAVIOUR OF the liquid is efficiently cooled and agitated, alcohol extracts from the crudo product a considerable quantity of tarry matter. The substance formed by dehydration of the bromonitroso-corn- pound is sparingly solrible in cold, but readily in boiling alcohol, from which i t crystallises in long, lustrous, transparent needles ; it is readily soluble in benzene. 0.2460 gave 0.4383 CO, and 0.1323 H,O. 0.2394 ,, 12.3 C.C. moist nitrogen at 21' and 756 mm. N=5*82. ,0*1977 ,, 0.1508 AgBr. Br = 32.46.C,oHI,OKBr requires C = 49.18 ; H = 5.74 ; N = 5.74 ; Br = 32.79 per cent. It has no definite melting point,, but shrinks and darkens at about 210°, becoming completely charred at 230'; it is slightly volatile on the water-bath, and sublimes in minute, transparent needles. The derivative does not give Liebermann's reaction, and is saturated towards bromine in chloroform, but a hot solution in dilute sulphuric acid quickly reduces potassium permanganate. Warm con- centrated nitric acid decomposes it, liberating gas, but hot concentrated sulphuric acid and boiling pyridine art! without action on it. As already stated, this compoiind is destitute of rotatory power. A 4 per cent. solution in benzene and a 1 per cent. solution in alcohol were examined in a 2-dcm. tube and found to be inactive.C= 48.58 ; H= 5.97, Conversion. of the Compound, CloHl,ONBr, into an Isomwide. The compound, C,oH1,ONBr, was powdered and covered with con- centrated hydrochloric acid, which was then boiled during several minutes; on dissolving the product in hot water and allowing the filtrated liquid to cool, colourless needles were deposited. This modification is also obtained by boiling an alcoholic solution of the compound with a few C.C. of concentrated hydrochloric acid, and crystallises from alcohol in large, transparent, six-sided plates ; it melts at 240' to a colourless liquid which does not decompose, and is slightly volatile a t 100'. 0.2548 gave 0.4596 CO, and 0.1347 H,O. 0.3633 ,, 18.1 C.C. moist nitrogen at 24' and 769 mm. N = 5.65. 0.2358 ,, 0.1830 AgBr.BF = 32.84. C,,H,,ONBr requires C = 49.18 ; H = 5.74 ; N = 6-74 ; BY= 32.79 per cent. The substance does not give Liebermann's reaction, and behaves like a saturated compound towards bromine dissolved in chloroform, and also towards a hot solution of potassium permanganate; it under- C = 49.19 ; H = 5.87.CAMPHOROXIME TOWARDS POTASSIUM HYPOBROMITE. 1147 goes no change when a solution in glacial acetic acid, or alcoholic hydrochloric acid, is boiled with zinc dust. It resembles the first modification in being optically inactive, but differs from it in its be- haviour towards benzoic chloride, with which it yields a benzoy1 derivative. This crystallises from alcohol in lustrous scales and melts at 174-176O. 0,2280 gave 0.1323 AgBr. €31. = 22-82.0.1998 ,, 0*10'70 AgBr. B r = 22.78. CI7H,,O,NBr repires Br = 33.00 per cent, Behavioui* of the Compounds, C,,H1,ONBr, towcwds Caustic Soda. A boiling, aqueous solution of caustic soda eliminates hydrogen bromide and carbon monoxide from the compound, C,,H1,ONBr, and from its isomeride, giving rise to a nitrile of the formula C,H13N. 100 grams of the finely powdered substance were heated with a solution of 40 grams of caustic soda in 300 C.C. of water; the operation was conducted in a reflux apparatus on the water-bath and continued during half an hour. A volatile oil soon appenred in the condenser, and the suspended solid aggregated to a pasty mass beneath the liquid. After the period specified, the condenser was rearranged for distillation, and :L current of steam was passed through the alkali until the bromo-compouiid mas completely decomposed.On extracting the distillate with ether, drying the extract with calcium chloride, and evaporating the ethereal solution, 50 grams of the nitrile were ob- tained ; the aqueous residue in the distillation flask was concentrated on the water-bath and yielded 6 grams of the solid amide described below. The nitrile is a limpid, colourless oil having an agreeable, camphor- like odour, it boils at 198-195O under 760 mm. pressure, and has a sp. gr. 0.9038 at 24". 0.2213 gave 0.6466 CO, and 0,1940 H20. C = 79.68 ; H = 9.74. 0,1560 ,, 14.1 C.C. moist nitrogen a t 20.5' and 764 mm. N = 10.37. C9H1:,N requires C = 80.00 ; H = 9-63 ; N = 10.37 per cent. The substance reduces n cold solution of potassium permanganate instantly, and also decolorises bromine dissolved in chloroform.A specimen examined in a 2-dcm. tube was feebly dextrorotatory, giving a,, +Oo 46', an angle so small, in view of the inactivity of the original compound, as to suggest the presence of some optically active impurity. In view of the fact that the elements of hydrogen bromide and carbon monoxide are withdrawn fram the compound, CloH1,ONBr, by the action of caustic soda, it became necessary to test the alkaline1148 FORSTER : CAMPHOROXIME. PART 111. residue in the distillation flask for sodium formate. The liquid was accordingly acidified with dilute sulphuric acid, and a current of steam passed through it. Formic acid mas recognised without difficulty in the distillate, which had a faint, pungent odour, and was strongly acid towards litmus ; silver nitrate gave a precipitate undergoing immediate reduction on heating, and a specimen of the characteristic lead formate was obtained. H9drolysis of the Xtvile.25 grams of the nitrile mere heated with a solution of 20 grams of caustic potash in alcohol during 30 hours in a reflux apparatus. Water was then added to the liquid, from which alcohol mas removed by evaporation ; a yellow oil floated on the surface, and rapidly crystallised as i t cooled. The product mas collected, drained on porous earthenware, and recrystalliked from boiling light petroleum. 0.2117 gave 0,5479 CO, and 0.1913 H,O. 0.2235 ,, 18.4 C.C. moist nitrogen at 24' mcl $69 i i m . N = 9.34. C,HI,ON requires cl = 70.59 ; H = 9.80 ; N = 0.15 per cent.The amide is scarcely soluble in cold, but dissolves more freely in Poiling petroleum, from which it separates in highly lustrous needlw melting a t 90"; it dissolves readily in alcohol, and is also soluble in boiling water, crystallising in flat, lustrous needles as the liquid cools, Belmviouy towards IIydrocA loric Acid .-The recrys talli sed amide dis- solved freely in cold concentrated hydrochloric acid, but on boiling the solution in a reflux apparatus it rapidly became turbid, owing to the separation of an oil ; the latter immediately crystallised on cooling the contents of the flask. On collecting the product with the aid of a filter pump, it was found that crystallisation from boiling water con- taining a' little sodium carbonate yielded a substance having the empirical formula of the original smide.C= 70.58; H= 10.04. 0*1S12 ,, 0.4663 CO, ,, 0.1613 H,O. C=70*17 ; H-9.89. 0*2000 gave 0.5145 W2 and 0.1759 H,O. Moreover, the compound crystallised in highly lustrous needles exactly resembling the substance from which it was obtained. It melted, however, at 139-1 SO3, the melting point of isolauronolamide (G. Blanc, Compt. ?*end., 1S96, 123, $49). During the conversion of the amide melting at 90' into isolauronol- amide, colourless crystals collected in the condenser. These were analysed, with the following result : cf = 70.16 ; H= 9.77. C9H,,0N requires cf = 70.59 ; H = 9.80 per cent. 0.1714 gave 0.4399 GO, and 0.1408 H,O. C = 70.00 ; H = 9.13. C,H,,O, requires cf = 70.13 ; I3 = 9.09 per cent.OPTICAL ACTIVITY OF DERIVATIVES OF RORNTLAMINE. 1149 The substance melted at 132-133' ; a solution in chloroform was in- different towards bromine, but when dissolved in sodium carbonate, the acid decolorised potassium permanganate instantly. This is the behaviour of isolauronolic acid, and i t was found that the melting point of the preparation obtained in the manner just indicated was not depressed by admixture with R specimen of isolauronolic acid sent t o me for the purpose of comparison by Prof. 'IV. H. Perkin. The action of hydrochloric acid on the amide melting at 90" pre- cludes the use of this agent for the purpose of hydrolysis. Unfortu- nately, however, alcoholic potash is almost without action on the sub- stance. In one experiment, 10 grains were heated during 50 hours with 8 concentrated solution of caustic potash iu alcohol, and practically the whole amoiint of the amicle was recovered on dilution with yater and evaporation. On heating 5 grams with 15 C.C. of a 50 per cent, aqueous solution of potash in a sealed tube at 120' during 6 hours, and removing the unaltered amide, the aqueous liquid yielded on acidifica- tion about 0.5 gram of an oily acid; f o r reasons already stated, it seems probable that this compound is campholytic acid (Walker, Trans., 1893, 63, 495), and further attempts to identify it are being made, ROYAL COLLEGE OF SCIENCE, LOKDON, SUUTH KCSSISGTOX, S.W.