OF CLOSED CARBON-CHAINS. 215 XXL- The Synthetical Formation of Closed Carbon-chains. Part V. Experiments on the Synthesis of Heptamethylene-derivatives. By PAUL C. FREER Ph.D. and W. H. PERKIN jun. Ph.D. WHEN ethylic malonate is treated with methyltetramethylene dibro-mide the only product of the reaction is ethylic methylpentamethyl-enedicarboxylate but when methylpentamethylene dibromide is used, besides ethylic methylhexamethylenedicarboxylate a considerable quantity of a second substance is formed which is the product of the action of 1 mol. of methylpentamethylene dibromide on 2 mols. of ethylic malonate thus :-2(COOC,H5),CHNa + CH,-CHBr*[CH2],*CH2Br = (COO C,H5 )&H*CH (C H3)*[CH2],*CH ( COOC,H5)2 + 2NaBr. This ethereal salt for which we propose the name ethylic isohep-tane-wzwz-tetracarboxylate is converted by hydrolysis into the corre 2 16 FREER AND PERKIN SYNTHETICAL FORMATION sponding acid and this on heating t o 200" is split up into carbonic anhydride and a new acid of the succinic series (methylazelaic acid)-(C 0 OH) ,CH*CH ( CH3) *[ C H,] 1' C H( C 0 OH) 2 = Isoheptanetetracarboxylic acid.COOH*CH,.CH(CH3)*[ CH,],*COOH + 2C0,. Methy lazelaic acid. Ethylic isoheptanetetracarboxylate was for these researches of special importance because as will be seen from a glance a t its formula, it contains two hydrogen-atoms which from their position with regard to the carb-ethoxyl-groups are capable of being displaced by sodium, forming a disodium compound of the following formula :-(COOC,H,),CNa~CH(CH,)~[CH,l,CNa(COOC,H,)2.This disodium compound when treated with iodine or bromine should be converted into ethylic methylheptamethylenetetracarbo-xylate,* thus :-( C 0 0 C,H,) ,CNa-CH ( CH,) - [ CH,] 4- CNa( C 0 0 C2H5) + Br = CH2.C H ( C H3) -4 ( C 0 0 C2H5) 2 C H d I + 2NaBr. 'CH?-CH,--C (COOC,H,), Methylheptamethylenetetracarboxylate (1 1 2 2 ) . This ethylic salt on hydrolysis would then yield the corresponding t,etracarboxylic acid which on heating to 200" would be converted into methylheptamethylenedicarboxylic acid (1 2) and carbonic anhydride, thus :-CH,.CH( CH,)-C( COOH), - CH2( I \CH,-CH,--C( COOH), Methylheptamethylenetetracarboxylic acid (3 1 1 2 2). C H,* CH ( C H3) -CH* C 0 O H CH,/ I + 2 c 0 . \cH,-cH -CH.CO OH MethylheptamethylenedicaPboxylic acid (3 1 2).TO prove that such a change had taken place it would be only necessary t o show (1) that the resulting methylheptamethylenedicarb-oxylic acid differed in its properties from the methylazelaic acid produced by the hydrolysis of ethylic isoheptanetetracarboxylate * Compare the formation of ethylic teti*amethylenetetracarboxylate from ethylic but~~e-wzw,-tetracarboxylate (Trans. 51 IS) also of ethylic pentamethylene-tetracarboxylate from ethylic pentane-wzw2-tetracmboxylate (Trane. 51 240) OF CLOSED CARBOS-C,HAINS. 217 before its treatment with sodiiim and bromine ; and (2) that the re-sulting acid was capable of forming an anhydride thus proving that the two carboxyl-groups which at first were separated by seven carbon-atoms were now in the ortho-position.Two careful experiments were tried with the object of carrying out this synthesis (bromine being used) but although from the decolori-sation of every drop of bromine as it came in contact with the sodium compound it seemed as though the decomposition had taken place in the way desired on examining the product it was found that no heptamethylene-ring had been formed. The resulting ethereal salt was a mixture containing a considerable quantity of reqenerated ethylic isoheptanetetracarboxylate and some very high-boiling complex products. It is impossible a t the pre-sent stage of these experiments t o explain what really takes place in a reaction of this kind ;* the only clear point is that as far as we could tell no trace of a heptamethylene-derivative is produced.This research does not of course prove that a closed carbon-chain of seven atoms cannot be formed ; but it would nevertheless appear to throw doubt on the existence of a chain of these dimensions. Experiments are being carried on the results of which it is hoped will clearly settle this important point. E thy lie Isohept artetetracarbox y late, (C 0 0 CZH,) ZC H a CH (CH,). [ C H?]4* C H (CO 0 CZH,) . When the product of the action of methylpentamethylene dibromide on ethylic malonate is distilled as described in the previous paper (p. 206) ethylic me thylhexamethylenedicarboxylate passes over, whilst a thick yellowish oil remains behind consisting of crude ethylic isoheptanetetracarboxylate. If this crude residue be submitted to fractional distillation under a pressure of 60 mm.nearly the whole of it will pass over without the slightest decomposition between 265" and 28S0 and on once or twice refractioning the oil is easily obtained pure boiling at 273-276". Analysis. 0.1808 gram substance gave 0.3970 gram GO and 0.1408 gxam HZO. Theory. C 2 0 ~ 3 4 0 8 . Found. C 59-70 per cent. 59.83 per cent. H 8-45 , 8.65 ,, 0 31.84 , 31.52 ,, * Compare for similar experiments Kipping (this vol. pp. 22 and 23). POL. LIII. 218 FREER AND PPERKIN SYNTHETICAL FORMATIOX E thylic isoheptanetetracsrboxylate is a thick colourless syrup boiling at 273-276" (60 mm.). When dissolvedin ether and treated with 2 mols. of sodic ethylate, a yellowish-whit,e sodium compound is precipitated. Sereral attempts were made to nnalyse this but it was found to be impracticable, owing t o its being so soluble in ether and so bygroscopic.Methylaxe laic Acid C 0 OH*CH,*CH (CH,)* [ CHz] 5* C 0 OH. When treated with alcoholic potash ethylic isoheptanetetracarb-oxylate is readily hydrolysed. I n carrying out this hydrolysis, 20 grams of the pure ethereal salt was mixed with a solution of 20 grams of pure potash dissolved in pure methyl alcohol and boiled in a flask connected with a reflux apparatus for about six hours. The excess of alcohol was then distilled off the residue dissolved in water, the resulting colourless solution neutralised with dilute sulphuric acid and evaporated on a water-bath till quite free from alcohol and ether. Excess of sulphuric acid was then added and the isoheptane-tetracarboxylic acid extracted at least 20 times with pure ether.The ethereal solution after drying over calcic chloride and evaporating, deposited the free acid as a thick colourless syrup which was not analysed b u t a t once converted into methylazelaic acid. I n order to do this the flask containing the isoheptanetefracarb-oxylic acid was heated in a metal bath slowly to 200" and kept a t that temperature until the evolution of carbonic anhydride had entirely ceased. The resulting brownish-coloured oil was dissolved in a little water boiled with a small quantity of animal CharcoaI, aud the almost colourless solution evaporated on a water-bath. As however the residue even after standing for some days over sulphuric acid in a vacuum showed no signs of crystallisation it was further purified by conversion into the ethereal salt.For this purpose the crude substance was dissolved in pure ethyl alcohol, saturated with hydrogen chloride and allowed to stand for some hours. Water was then added the ethereal salt extracted with ether washed with dilute carbonate of soda solution the ether distilled off and the residue fractioned under reduced pressure (100 mm.). In this way it was easily obtained pure as a thick oil boiling at 212-215" (100 mm.). Analysis. 0.1655 gram substance gave 0.1500 gram H,O and 0.3936 gram GO,. Cl'IH260-I. Found. Theory. 65.11 per cent. C . . . . . . . . H . . . . . . 10-08 , 10.07 ,, 0 . . . . 24-81 , 25.04 ,, 64.89 per cent OF CLOSED CARBON-CHAINS.219 The ethylic salt of methylazelaic acid is a colourless liquid of peculiar odour and boils at 212-215" under a pressure of 100 mm. It is isomeric with ethylic sebate which boils at 307-308" under ordinary pressures. In order to obtain methylazelaic acid the ethereal salt was gently boiled with a slight excess of a solution of potash in pure methyl alcohol f o r two hours the excess of alcohol distilled off the product dis-solved in water and the solution evaporated nearly to dryness. The residue was then dissolved in a little water acidified with dilute sulphuric acid and extracted two or three times with pure ether. The ethereal solution after beine; carefully dried over calcic chloride was evaporated and in this way the new acid was obtained as a colourless syrup; this after standing for some days over sulphuric acid in a vacuum solidified to a hard cake of crystals.These were freed from a small quantity of oily mother-liquor by spreading out on a porous plate and the acid was thus obtained quite colourless. After drying over sulphuric acid in a vacuum it gave the following numbers on analysis :-0.1334 gram substance gave 0.1070 gram H20 and 0.2908 gram coz. Theory. C10H1804. Found. C 59.41 per cent. 59.44 per cent. 0 31.68 ? 31-65 ,, H 8.91 , 8.91 ,) Methylazelaic acid thus prepared melts at 43-44' and when heated in small quantities in a test-tube appears to distil without decomposition. It is fairly easily soluble in boiling water and on cooling the liquid becomes milky owing t o the separation of the acid in oily drops.It is readily soluble in ether alcohol benzene and chloroform but cannot be recrystallised from any of these solvents, as on evaporating its solutions it is invariably obtained as a syrup which only crystallises again after standing for some time over sul-pliuric acid in a vacuum. Methylazelaic acid is isomeric with sebacic acid (m. p. 197") and heptylmalonic acid (m. p. 97-98"}. Balts of Methylazelaic Acid. Silver #aZt.-To prepare this salt the pure acid was dissolved in a little dilute ammonia the solution allowed to stand over sulphnric acid in a vacuum till free from excess of ammonia and the silver salt precipitated by the addition of nitrate of silver. It is thus obtained as a white amorphous mass which after collecting on a filter washing Q 220 FREER AND PERKIN SYNTHETICAL FORMATION well with water and drying over sulphuric acid in a vacuum gave the following numbers on analysis :-0.2380 gram substance gave 0.0833 gram H20 0.2507 gram CO,, and 0.1233 gram Ag.Theory. C10%04Ag2. Found. C 28-84 per cent. 28.80 per cent. H 3.84 , 3-89 ,> 0 15-38 , 15.51 ,, Ag 51.92 , 51-80 ,, 'If a neutral solution of the ammonium salt be treated with various reagents it behaves in the following way :-Calcic Chloride. Cupric Sulphate . . Lead Acetate Zinc Sulphate Bzric Chloride hfagnesic Sulphate Cobalt Nitrate Nickel Sulphate . . Added to a cold strong solution of the am-monium salt gives no precipitate ; on warm-ing however the calcium salt separates as a white curdy precipitate which when examined under the microscope presents very much the appearance of potato-starch.Gives a bluish-green precipitate almost in-soluble in water. A white amorphous precipitate. Gives no precipitate even in strong solutions. On warming however the zinc salt separates as a curdy-white mass. The free acid dissolves readily in baryta-water forming an easily soluble salt not precipitated by boiling. Gives no precipitate. Gives no precipitate. Gives no precipitate in the cold; on gently warming the solution a pink precipitate separates which on boiling becomes reddish-violet. When added to a hot strong solution produces a pale-green (almost white) precipitate. Action of Bromine 01% the Disodium Compound of Ethylic Isoheptane-tetrcrcarboxy late.This experiment which was instituted in the hope of obtaining a neptamethyleiie-derivative as mentioned in the introduction was cnrried out in the following way and with the following quanti-ties : OF CLOSED CARBON-CHAINS. 221 Expt. I. Expt. 11. isohePtanetetra-} 17.00 grams. 22-78 granls. carboxylate . Sodium 1.93 , 2.60 ,, Bromine 6.72 , 9-00 ,, In both experiments the sodium was dissolved in as little absolute alcohol as possible the resulting sodic ethylate diluted with a large quantity of pure dry ether (about 100 C.C. in Experiment I and 200 C.C. in Experiment II) and mixed with the ethylic isoheptane-tetracarboxylate. This caused the formation of a small amount of a yellowish flocculent precipitate but the greater part of the disodium compound remained in solution.This mixture was cooled with ice, and the bromine added to it drop by drop the whole being well agitated during the operation. The resulting colourless product was then well washed with water, the ethereal solution evaporated and the residual oil (which in Experiment 11 weighed nearly 22 grams) hydrolysed by boiling with a solution of potash in methyl alcohol. As soon as the hydrolysis was complete the alcohol was distilled off water added the solution acidified with dilute sulphuric acid and several times extracted with ether. After drying over calcic chloride and evaporating off the ether a thick almost colourless syrup remained which was now heated to 200" to cause the tetracarboxylic acid to split up into dicarboxylic acid and carbonic anhydride.The residue which was slightly brownish was then converted into its ethylic salt by treat-ment with ethyl alcohol and hydrogen chloride In this way a brownish oil was obtained which on fractioning under reduced pressure (100 mm.) distilled for the most part between 'LOO" and 260', leaving a small quantity of a dark brown residue. On repeated fractioning rather more than one-half of this oil distilled bet ween 210" and 220". This oil was not analysed but at once hydrolysed and the free acid examined. The whole quantity was boiled with a solution of potash in methyl alcohol for four hours and the acid isolated in the usual way by acidifying with dilute sulphuric acid and extracting with pure ether. I n this way a considerable quantity of a nearly colourless syrup was obtained which on standing for some days over sulphuric acid in a vacuum solidified almost completely.The cake of crystals was purified from a little oily mother-liquor by spreading out on a porous plate and after a few days became perfectly hard and colonrless. This substance on examination proved to be methylazelaic acid. It melted at 43-44," showed all the properties of this acid and gave the following results on analysis : 222 RUCRER ON THE 0.1351 gram substance gave 0.1075 gram H20 and 0.2935 gram co2. Theory. C10H1804. C 59.41 per cent. H 8.91 ,, 0 31-68 ,, I f methylheptamethylenecarboxylic product of these reactions it would on hydrogen chloride as described above, the boiling point of which would not Found.59.25 per cent. 8.84 ,, 31.91 ,, acid had been present in the etherification with alcohol and have yielded an ethereal salt, have differed very much from that of ethylic methylazelate. By the hydrolysis of the fraction of this ethereal salt boiling a t 210-220" methylazelaic acid was obtained but as far as we could see no trace of any other acid was present. I n order however to be more sure of this result the higher and lower fractions of this ethereal salt (200-260") were also submitted to hydrolysis and in this way a syrupy acid was obtained which on standing deposited a small quantity of methylazelaic acid. The mother-liquors from the crystals were now heated in a met,al-bath for some time a t 250-280" in the hope that i f any methylheptn-methylenedicarboxylic acid were present it would in this way be converted into its anhydride. On t'reating the product with dilute ammonia however it readily dissolved showing that no such change had taken place. From these results therefore it is evident that the action of bromine on the disodium compound of et'hylic isoheptaaetetra-carboxylate no heptamethylene-derivative is formed