398 LXII.-Orb Dihydroqbeiizoic Acids and Ioclosalicy lic Acids. By ALEX. K. MILLER Ph.D. OF the six acids of the formula C6H3(OH),.COOH theoretically possible five are already known and it was with the view of com-pleting the series that the following research was undert,aken. The acid remaining as yet undescribed is that represented by the for-mula,-COOEI and may be conveniently termed catecho~-o1-t7Locnrbox?jlic acid. In order to prepare this acid I have tried two different methods in the one case starting from catechol (pyrocatechin) and in the other from salicylic acid. It is evident that if the same acid should he formed both by the introduction of a carboxyl group into catechol, and by replacing a hydrogen-atom in salicylic acid by hydroxyl this acid must necessarily have the structure represented by the above formula.Preparation of Dikydroxybenzoic Acids f y o m Catechol. I n order to prepare dihydroxybeneoic acids from catechol the method described by Senhofer and Brunner for the direct introduc-tion of carboxyl into phenols &c. ( W e n . Akad. Ber. 1879 2 Abth., 504) was made use of. According to this method a phenol is heated in sealed tubes for several hours to a temperature of about 110" with a concentrated solution of ammonium carbonate. I n this way Sen-hofer and Brunner obtained from resorcinol the following two dihydroxjbenzoic acids :-OH OH I n tho first of these two acids the carboxyl takes up the ortho-and para-positions respectively to the two hydroxyl groups and in the second acid the ortho-position to both hJ-droxyl groups.The symmetrical acid MILLER ON DIHYDROXYBENZOIC ACIDS ETC. 399 CGOH was not formed in tho reaction. St,arting from catechol there are only acids possible namely protocatechuic acid, two dihydroxybenzoic OH 0 I€ and since in the former the carboxyl is in the para-position to one of the hydroxyl groups and in the latter in the ortho-position to a hydroxyl group it was thought possible that both acids might be formed. 1 pftrt catechol 4 parts ammonium carbonate and 5 parts water were heated in sealed tubes a t a temperature of 130-140" for 14-16 hours. The tubes were then opened and after nearly neutralising with hydrochloric acid the liquid was filtered and the unaltered catechol extracted with ether. An excess of hydrochloric acid was then added to liberate any dihydroxybenzoic acid t h a t might have been formed and this was separated from the ammonium chloride by again shaking up with ether.After evaporating the ether a dark strongly acid residue was left behind the weight of which amounted to about one-third that of the catechol employed. After repeated crystallisations from hot water, this residue was found to consist of two distinct acids which had, however been formed in very unequal proportions. One of these, which formed by far the greater part of the product was found to be protocatechuic acid as seen from the following properties :-It crys-tallised in needles and plates with 1 mol. of water of crystallisation, which it lost a t loo" and it melted at 199'.With lead acetate it gave in aqueous solution a white flocculent precipitate and with ferric chloride an intense blue-green colour which changed to red on the addition of sodium carbonate. On heating it with pamice-stone, carbonic anhydride was given off and a sublimate of catechol was obtained. The catechol was recognised by the characteristic green colour which it gives with ferric chloride changing to violet on addi-tion of sodium carbonate ; also by the precipitate which it gives with lead acetate. The second dihydroxybenzoic acid was found in the mother-liquor from the protocatechuic acid. It had been formed only in minute ::OH The experiment was carried out as follows:-It melted a t 100" 400 MILLER OK DIHYDROXYBENZOIC ACIDS quantities and could therefore not be obtained in the pure state or of constant melting point this difficulty being further increased by its partial decomposition below the melting point.The highest melting point obtained was 192". This acid differed from protocatechuic acid in its crystalline appear-ance and in its colour reaction with ferric chloride producing a pure blue coloration which on addition of sodium carbonate changed to violet-red. By the slow evaporation of its solution in ether the acid was obtained in nodules which presented an appearance totally dis-tinct from that of the needles of protocatechuic acid. On account of the very poor yield of the second acid only a single analysis could be made. 0.0979 gram substance gave 0.1980 gram CO and 0.0375 gram HZO. Calculated for C;H,04.Found. C = 54.54 per cent. H = 3.90 , 4.25 ,, 55-15 per cent. 0 = 41.56 , -100~00 Although the small quantity of this body which was at my disposal allowed so few experiments to be made they are still sufficient to show that two dihydroxybenzoic acids can be obtained from catechol, one of which is protocatechuic acid. But since two only of these dihydroxy-acids can be derived from catechol the only formula possible for the second acid is-OH and that this constitution is the correct one is further confirmed by the experiments described below. In the second method employed for obtaining the acid just men-tioned salicylic acid was submitted to the direct action of iodine and the resulting iodosalicylic acids were converted into dihydroxybenzoic acids by melting with potash.Although different chemists have already worked upon this reaction, the results obtained differ so much among themselves that it appeared desirable to repeat the investigation. Lautemann (Annalen 120 301) for instance prepared iodosalicylic acid by boiling a solution of salicylic acid and iodine in Icohol. The acid he obtained melted a t 196". On heating with pctash it gave an oxysalicylic acid (Le. dihydroxybenzoic mid) which he characterise AXD IODOSALICTLIC ACIDS. 401 a s follows :-It melted a t 193" crystnllised anhydrous and gave with ferric chloride a deep blue colour changing t o violet on addition of sodium carbonate. Wit,h acetate of lead a yellowish-white precipitate was produced. On heating his oxysalicylic acid with pumice-stone, Lautemann obtained a distillate which hd found to be a mixture of catechol and quinol.Liechtli (Amzalen. Suppl. 7 133) made iodosalicylic acid by heating salicylic acid in aqueous solution with iodine and iodic acid. He gives 184" as the melting point of his acid. On melting his mono-iodosalicylic acid with potash he obtained a dihydroxybenzoic acid which melted at 183". Like Lautemann's acid it gave a deep blue colour reaction with ferric chloride. Demole (Bey. 7 1437) prepared iodosalicylic acid according to Liechti's method and confirmed his melting point. He also converted the iodosalicylic acid into dihydroxybenzoic acid and here again obtained the same results as Liechti. On heating his dihydroxybenzoic acid with pumice-stone Demole obtained either pure quinol or a mix-ture of the latter with small and rariable quantities of catechol.Be says that more or less catechol is formed according to the temperature a t which the acid is distilled and that in some experiments he found scarcely any ; so that since quinol is the chief and essential product of the reaction it seems fair to suppose that were dealing with quinolcarboxylic acid : OH Demole and also Liechti Demole examined further the action of melted potash on di-iodo-salicylic acid and through the unexpected results which he obtained, he thought he could explain the discrepancies between his own and Lautemann's results. From pure di-iodosalicylic acid he obtained :t mixture of two dihydroxybenzoic acids (instead of a trihydroxybenzoic acid as he expected) one of which was quinolcarboxylic acid, OH COOH Demole found further that a mixture of monoiodosalicylic acid with about b di-iodosalicylic acid melted a t 196" i.e.a t the same temperature which Lautemitnn gave for his monoiodosalicylic acid, supposed to be pure. On melting this mixture with pot,ash Demol 402 MILLER ON DIHYDROXYBENZOIC ACIDS obtained a mixture of quinolcarboxylic acid and protocatechuic acid, the latter resulting as already mentioned from the di-iodosalicylic acid. By the action of heat on these two dihydroxybenzoic acids both gave off carbonic anhydride the former yielding quinol and the latter catechol. In this way Demole tried to explain the high melting point of Lautemann’s iodosalicylic acid and the fact of a considerable quantity of catecliol being formed on heating his dihydroxybenzoic acid.Goldberg (Dissertation Wurzburg 1878) prepared iodosalicylic acid from salicylic acid by means of the diazo-compound. His acid also melted at 196” and yielded a dihydroxybenzoic acid of melting point 197” by the dry distillation of which Goldberg obtained pure quinol so that there can be no doubt that he really had pure quinolcarboxylic acid. The acid is characterised by giving a deep blue colour-reaction with ferric chloride also by not being precipitated by acetate of lead. Although the iodosalicylic acids of Lautemann and Goldberg agree in melting point important differences are found in the dihydroxy-acids obtained from them and in the products of their decomposition, Lauternanu’s acid yielding principally catechol which was however, always accompanied by quinol while Goldberg’s acid yielded pure quinol.I n order to decide whether Lnutemann’s acid was identical with Goldberg’s or with an isomeride having the same melting point or, finally a mixture of mono- and di-iodosalicylic acids as imagined by Demole I have prepared iodosalicylic acid by Lautemann’s method (see page 400). For the separation of the mono- from the di-iodosalicylic acid and from unaltered salicylic acid the mixture was boiled with water and barium carbonate and the barium salts so obtained were repeatedly crystallised from hot water. I n this way it is comparatively easy to obtain a product which analysis shows to be barium mono-iodosali-cylate.That the same was however not a definite body was shown by the fact that the products of different preparations had different melting points ; also that in recrystallising the barium salts the iodo-salicylic acid separated from different fractions showed the same chemical composition though different melt’ing points. Finally this method had to be given up and the attempt was made to get a pure product by crystallising the acid itself‘ from water. Although on account of the very slight solubility of iodosalicylic acid in water, this method has the disadvantage that large quantities of liquid have to be employed it seems to be the best for the separation of the isomeric acids. I n preparing iodosalicylic acid by Lautomann’s method two isomeric acids are in fact formed which melt a t nearly the same temperature AND IODOSALICYLIC ACIDS.403 They differ however in crystalline appearance and in their solubility in water and yield on melt,ing with potash two different dihydroxy-benzoic acids as will be seen below. The separation and purification of these two iodosalicylic acids was systematically carried out as shown in the following scheme :-c 5 4a c 0 m B 404 MILLER ON DIHYDROSYBENZOIC AClDS This scheme represents bp way of example a small part of that made up in the course of the work which is much too lengthy and complicated to reproduce in full. The portion communicated will suffice to show to some extent the difficulty of separating the two acids. The following short explanation will serve to make this scheme intelligible :-A small fraction of the whole iodosalicylic acid mixture A (melting at 171-175') was dissolved in hot water.Tile crystals a (melting a t 172-173") separated out on cooling while the evaporated mother-liquor yielded the crystals /3 (melting a t 181-1S6°). By the further treatment of a in the same fashion y and 6 were obtained, &c. &c. the find result being two crops of constant melting point, the more difficultly soluble acid melting a t 157" and the more easily soluble a t 1%". The former acid (197" m. p.) is identical as will be hereafter shown, with that obtained by Goldberg. It is para-iodosalicylic acid and has the constitution-COOH (1) c~H,.L/oH (a) 'I ( 5 ) It crystalliees from water in splendid long needles.a violet coloration with ferric chloride. Its solution gives On analysis the following numbers were obtained :-Calculated for C,H,I(OH).COOH. C = 31.82 per cent. H = 1.89 ,, I = 48.10 ,, 0 = 18.19 ,, Found. 31-68 per cent. 1-92 ,, 48.12 ,, The barium salt of this para-iodosalicylic acid obtained by boiling its aqueous solution with barium carbonate crystallises with 4 mols. of water of crystallisation in warty conglomerations of scales. The dry salt requires for solution 120-125 parts water a t 8". Conversion of Para-ioclosalicy 1 ic Acid into Dihydroxy benxoic Acid. The moist iodosalicylic acid was heated with an excess of potash till decomposition was complete. This was ascertained by acidulating a small portion with hydrochloric acid which produced a precipitate so long as iodosalicylic acid remained undecomposed.The alkaline mass was left to cool dissolved in water and treated with an excess of hydrochloric acid and the liberated dihydroxybenzoic acid was then separated by shaking out with ether. On evaporating the etherea AND IODOSALICPLIC ACIDS. 405 solution a brown residue was obtained which was purified by crystal-lisation from water. The acid crystallises in anhydrous needles. I t s aqueous solution gives with acetate of lead 980 precipitate with ferric chloride a deep blue coloration changing to red on addition of sodium carbonate. This red colour is however very unstable and is at once destroyed by an excess of the reagent. The acid melts a t 200" i.e. 3" higher than the melting point given by Goldberg.There can however be no doubt that the two are identical and it may here be mid that, for recognising the different isomeric dihydroxybenzoic acids the melting points cannot well be depended upon first because most of these acids melt a t temperatures very close to one another ; and secondly because they for the most part begin to decompose either on melting or below their melting points, into carbonic anhydride and dihydroxybenzene. I n order better to establish the constitut,ion of this acid and its identity with that of Goldberg it was cautiously heated in an oil-bath to a temperature of 215". Carbonic anhydride was given off and a sublimate obtained of pure quinol which was identified by its melting point (169") and by its yielding the powerful and highly characteristic odour of quinone when warmed with ferric chloride.The absence of catechol was proved by the fact of lead acetate giving no precipitate. The barium salt of t h i s dihydroxybenzoic acid crystallised in rosette-like groups as described by Goldberg. In water it is very soluble, 1 part of salt requiring only 2.3 parts of water. On analysing the acid the following numbers were obtained :-Calculated for C = 54.54 per cent. H = 3.90 ,, C~HS(OH)~.COO H. Found. 54-96 per cent. 4-19 ,, From the undoubted constitution of this quinolcarboxylic acid i t is evident that the iodosalicylic acid from which it was obtained is also identical with that prepared by Goldberg and tliat it has the con-stitution-COOH (1) C6H,LOH (2).'I ( 5 ) The second or more easily soluble iodosalicylic acid obtained by the scheme of crystallisation referred to above (page 403) separated from its hot aqueous solution usually as an indistinct crystalline mass but could be obtained by very slow cooling in well-formed needles which, however have a very different crystalline appearance from those of para-iodosalicylic acid. It will be shown to be the ortho-iodosalicylic acid sought after 40 6 MILLER ON DIHYDROXYBENZOIC ACJDS This acid melts a t 198" i.e. one degree higher than the para-iodo-Both give a violet colour-reaction with ferric chloride. On analysis the following results were obtained :-salicylic acid. Calonlat~ed for C,H,T(OH).COOH. C = 31.82 per cent. H = 1.89 ,, I = 48.10 ,, 0 = 18-19 ) ) Found.31.91 per cent. 1-89 ,, 47.98 ,, For the readier coniparison of the two isomeric iodosalicylic acids, the barium salt of the last described acid was also made (see page 404). At 8" it requires for solution 190 times its weight of water and is con-sequently much less soluble than the para-compound. It crystallises with 3$ mols. of water in concentrically grouped needles. On melting this second iodo-salicylic acid (ortho-iodosalicylic acid) with potash a dihydrosybenzoic acid was obtained which by its colour reaction with ferric chloride could be easily mistaken for quinolcarboxylic acid but by its other properties was shown to be a distinct acid. Ferric chloride produced a deep blue colour which changed to violet-red on addition of sodium carbonate.This last colour is however distinguished from that which quinolcarboxylic acid gives by not being destroyed by an excess of the sodic solu-tion. This new dihydroxybenzoic acid differs further from quinolcarboxylic acid in its crystalline appemance and by sometimes containing water of crystallisation ; also by giving a precipitate with acetate of lead and by yielding on heating carbonic anhydride and catechol. From water it crystallises either in anhydrous warty masses or in Fell-formed needles with 2 mols. of water. On analysis the following numbers were obtained :-Calculated for C,H,O,. C = 54.54 per cent. H = 3.90 ,, Found. 54.70 per cent. 4.28 ,, By the slow evaporation of an ethereal solution of this acid i t was obtained in small nodules which had exactly the appearance of the acid obtained from catechol and ammonium carbonate (see page 399).The two are in fact identica,l ; with ferric chloride and sodium carbo-nate they both give exactly the same colour reactions; both give white precipitates with lead acetate and both decompose on heating into carbonic anhydride and catechol. In order to determine the temperatnre a t which decomposition commences the acid was mixed with powdered pumice and gradually The acid melts a t 204" AXD IODOSALIGPLIC ACIDS. 407 heated in an oil-bath a slow current of carbonic anhydride being a t the same time passed through the retort in which the mixture was con-tained. A sublimate of catechol began to be formed when the tem-perature had risen to 160-170”.This was resublimed between watch-glasses to free it from traces of undecomposed acid and was then found to consist of pure catechol. It melted a t 102-103” gave the characteristic green coloration with ferric chloride the colour chang-i n g to violet-red on adding sodium carbonate. With lead acetate it gave a white precipitate. The barium salt of this dihydroxybenzoic acid crystallises in small transparent well formed prisms which are difficultly soluble in cold water one part of the salt requiring a t 18” 95-100 parts water. The salt crystallises with 5 mols. of water. The fact that the above dihydroxybenzoic acid prepared from sali-cylic acid yields catechol on heating is of itself proof that this acid must have the constitution COOH Buk this constitution is also the only one possible for the acid which was obtained together with prntocatechuic acid by the introduction of a carboxyl-group into catechol (page 398).And since both of these methods have yielded one and the same product there cannot be the least doubt as to its constitution. Since in preparing the iodosalicylic acids Lantemann’s instructions have been followed it is in the highest degree probable. that Laute-mann was also dealing with a mixture of two isomerides. On fusing with potash he would in this case naturally have got a mixture of the two dihydroxybenzoic acids. In this way it is easy to explain how the distillate from his dihydroxybenzoic acids contained bolh catechol and quinol instead of assuming as Demole did that Lautemann’s m ono-iodosalicylic acid consisted principally of di-iodosalicylic acid.The low melting points of Liechti’s and Demole’s iodosalicylic and dihydroxybenzoic acids and the formation of small quantities of cate-chol by the distillation of the latter acid may also perhaps find their true explanation in the assumption that the acids prepared by Liechti and Demole also contained small quantities of the isomeric ortho-acid. The series of the six dihydroxybenzoic acids being now complete, I have compiled for comparison a table (pp. 409 410) showing their principal properties methods of preparation &c. The readiness with which these acids split up on heating seemR to be connected with the relative positions of the carboxyl- and hy-VOL. XLT. 2 408 MILLER ON DIHYDROXYBENZOIC ACIDS droxyl-groups to one another.It will be seen for instance that the acid which most easily gives off carbonic anhydride is the one in which the two hydroxyl-groups are in the ortho-position to the carboxyl-group. Then follow the acids in which the carboxyl is in the ortho-position to only one hydroxyl-group and last of all the most difficultly decornposible symmetrical acid. It will also he seen from the table that the solubility or insolubility of %he lead compounds of these acids depends upon the relative posi-tion of the two hydroxyl-groups to one another. Of the three phenols, C6E4(OH), catechol alone gives a precipitate with lead aceta.te and of the six acids C6H3(OH),.COOH none yield precipitates with acetate of lead except the two which are obtainedfrom catechol.I n conclusion I beg to thank Professor Wisliceniis in whose laboratory this research was carried out for valuable advice and assistance received during the progress of the investigation TAnr,E OF 1'1113 DIHTDROXYRE~-ZOIC ACIDS. Name. CO,Nn,Z t,he c.olollr being ~ -.I--1 2 3 Catzechol-ortho-car-boxylic acid. I 1 2 4 -a-Dihy-droxyben-zoic acid. I 1,2,5, By 1 From Q,uinolcar-boxylic acid. -Author. -Brunner and Senhof er. 4sher. Blomstrand. L'icmann and Parrisius. -Liechti n e -mole Gold-berg Author Mowski and Leppert. icllllofcr and Sarlcy . :-Catechol and arninonic carbonate. rodosalicylic acid. -__ Resorcinol mid ammo-nic carbon-ate. phonic acid.phonic acid. ronc. p-Crcsolsul-Tolnoldisul-Umbcllife--lo dosalicylic acid. Rromsalicylic acid. 3uinol and I< I i c'o,. Crystalline form and water oi crystallisa-tion. -_. Wart-like groups (an-hydrous). Keedles with 2&0. _I-Yeedles and plates with S 19 or 3H20. -Lnhydrous needles and prisms. Melting point. --204OC. de-composes -_e-LY4-2OO0 decomposes. according to Tiemann. 20t-206°, --197' accord-ing to Rakowski and Gold-berg. !0O0 accord-iilg t o A ut 1101'. Reaction with PepC1,. Deep blue coloration, which with CO,Na, changes to violet -red. The colour is not de-stroyed by excess of re-agent. Red colour. -Deep bl Lie colour, which changes to dirty red wit TABLE OF THE DIHYDR,OXYBENZOIC ACIDS. 1 3,4 techuic acid. -I__-39 Symmetri-cal dihj-droxyben-zoic acid. Prepared Crystalline form and water of cqstallisa-tion. Reaction with Fe2C16. Melting point. From -I-When di-lute violet j concentra-ted intense blue colora-tion. Resomino1 and mnnio-nic carbon-ate. Long needles with 1 mol. H20. Ip-Dihy-1 2 6 1 droxyben-I zOic acid-48-16'7". decomposes. 3enhofer and Yrunner. -Bromanisic acid. droxyben-zoic acid. lulphanisic acid. 2atechol and ammonium carbonate. lodo -p-hy---I-1 9 9 O . Barth. B1 ue-green coloration, vhnnging to red onaddi-tion of CO,Na2. Needles and plates mit,h 1 m01. H2O. I Protoca-Rlalin. Author. -No colora-tion. Barth and Senhofer. Disulphoben-zoic acid. Prisms and needles. 232-233"