100 MOIR : CYANOHYDROXYPYRIDTNE DERIVATIVES XI I.-Cyanohydq-ozypyridine Derivatives fyom Diuceto- nitrile. New Derivatives of q-lutidostyril. By JAMES MOIR, M.A., B.Sc., 1851 Exhibition Scholar of Aberdeen University . DIACETONITRILE was first prepared in 1889 by R. Holtzwart, in E. von Meyer's laboratory, by the action of sodium on acetonitrile in the presence of a diluent such as ether, which serves to keep the tempera- ture below that required to form the terrnolecular polymeride cyan- methine (J. p . Chem., 1889,39, [ii], 329). While attempting to make the latter compound for another purpose, I found that even if acetonitrile alone be used, diacetonitrile is almost the sole organic product (instead of cyanmethine) if the sodium be present in excess. During these experiments, in attempting to crystal- lise the diacetonitrile from hot water, I noticed that ammonia was evolved during the digestion of the solution on the water-bath, and that subsequently a different substance crystallised from the liquid.The formation of this substance, which is sparingly soluble in all the ordinary solvents and beautifully crystalline, had already been observed by Holtzwart, who made an extensive study of diacetonitrile. Although he analysed the compound and assigned to i t the formula C,H,ON,, unfortunately he did not succeed in elucidating its constitu- tion. The mechanism of the process by which it arises is, however, not difficult to imagine, if it be remembered that, as Holtzwart has shown, diacetonitrile has the constitution CH;C(NH,):CH.CN, and that it is easily converted by hydrolysis into the isodynamic form of cyanacetone, CH,.C(OH):cH.CN. If two molecules of the latter compound lose one of water, a compound of the formula C,H,ON,will be produced. This formula is that of an anhydride of cyanacetone; CH,* C:CH* CN CH,*C:CH* CN Holtzwart therefore proposed to write the formula >o ' von Meyer subsequently suggested the alternative formiila CH; E*GH,* CN NC*C*CO*CH,FROM DIACETONITRILE. 101 My experiments have led me to conclude that such formule afford no adequate explanation of the extreme stability and inactivity of the substance, and they seem to me to justify the conclusion that the compound is in reality 3-cyano-~-l~tidostyl.il: 7% or, more probably, a polymeride of that substance formed by a process analogous to that by which benzonitrile is converted into cyanphenine. Attempts to determine the molecular weight were frustrated by the insolubility of the substance, I n preparing diacetonitrile and the compound under discussion, the methods described by Holtzwart and by von Meyer mere in the main followed. As diluents of the acetonitrile, dry ether, benzene, and toluene were tried without much benefit.I n all cases, the yield of diacetonitrile leaves much to be desired. The best results are obtained as follows. Forty grams of acetonitrile (distilled over phos- phoric oxide or solid potash) having been covered with a layer of dry light petroleum (to exclude air), 10 grams of sodium in thickish slices are introduced gradually through the condenser.The action is very violent until the surface of the metal becomes coated; finally, the flask is heated during four hours on the water-bath. The mixture, having been transferred to a Buchner funnel, is thoroughly stirred, to separate the product from the sodium, which can then be mechanically removed. The solid-a mixture of sodium diacetonitrile with sodium cyanide-is mixed with just enough water to dissolve it ; diacetonitrile separates as an oil and may be completely recovered by extracting with benzene and then evaporating off the solvent. To prepare Holtzwart’s compound, the benzene extracts are digested with about 20 parts of water : as the benzene evaporates, ammonia is given off and the liquid becomes brown ; eventually it deposits needles of the condensation compound.The mother liquor, on digestion with water, yields a further quantity together with a red gum. The product is obtained practically pure by one crystallisation from glacial acetic acid. The loss caused by the formation of bye-products in this double condensation is so great that the yield of the final product is seldom over 8 per cent. of the acetonitrile used. The substance so obtained agrees on the whole with Holtzwart’s description, forming bundles of small, short needles ; it has an intensely bitter taste. It is equally soluble in boiling water and alcohol to the extent of about 1 per cent.; it is more soluble in boiling glacial acetic acid, but in boiling benzene only to the extent of 1102 MOIB : CYA NOHYDKOXYPYHIDPNE DERIVATIVES part in 600.I have to add the correction that the purified substance melts sharply at 293' (305' corr.), although it darkens somewhat above 280'. It can be sublimed without much loss a t a higher temperature. Holtzwart states that his compound melted '( oberhalb 230' "-a serious underestimate, as I have never observed a lower melting point than 260'' even in the case of the crude preparation. Holtzwart's formula was confirmed by the following analysis : It crystallises out easily on cooling these solutions. 0.1513 gave 0.35 96 CO, and 0.0752 H,O. C = 64.82 ; H = 5.52. 0.0855 ,, 13.7 C.C. moist nitrogen a t 13.5' and 750 mm. N = 18.63. C,H,ON, requires C = 64.79 ; H = 5.45 ; N = 18.95 per cent. Despite the presence of two nitrogen atoms, the compound is not basic and may be crystallised from aqueous acids; it does not combine with platinic chloride.It is easily soluble in alkali hydroxides, metallic derivatives being formed ; these can be isolated by adding excess of alkali, and crystallise well from a mixture of absolute alcohol and ether, although very soluble in spirit or acetone, The potassium derivative forms long, lustrous needles ; the sodium derivative, short,, opaque needles. That they are phenolic in character is shown by the fact that the addition of carbon dioxide or of ammonium salts to their solutions causes a precipitate of the original substance. Attempts were made to analyse these, but the results were vitiated by the rapid absorption of carbon dioxide during the drying; the figures are too low in consequence.0.2472 potassium derivative gave 0.1100 K,SO,. 0.4923 sodium derivative gave 0.1804 Na,SO,. 0.1329 ,, ,, dried in a vacuum, gave 19.7 C.C. moist K = 19.97. C,H70N,K requires K = 21.01 per cent. Na = 11-88. nitrogen at 13' and 746 mm. N = 17.2. C,H70N,Na requires N = 16.47 ; Na = 13.54 per cent. Holtzwart's compound is a substance of unusual stability, and is not (1) Prolonged boiling with a 10 per cent. aqueous or alcoholic solu- (2) Prolonged boiling with methyl iodide and sodium hydroxide. (3) Prolonged heating a t 120° with 70 per cent. sulphuric acid. (4) Heating at 80' with fuming sulphuric acid. ( 5 ) Prolonged boiling with acetic anhydride. It had previously been shown by workers in von Meyer's laboratory that it is not affected by acetyl chloride, hydroxylamine, nitrous acid, &c.It gives no coloration with nitrososulphuric acid. It is only slightly attacked by boiling dilute nitric acid and by permanganate, affected by tion of sodium hydroxide.FROM DIACETONITRlLE. 103 and although it at once reduces a solution of chromium trioxide in acetic acid, nothing definite can be isolated. It is also scarcely affected by boiling its solution in absolute alcohol with a large excess of sodium. The first clue to the nature of the substance was obtained by heating it with zinc dust; a distillate smelling like pyridina was obtained, but in too small a quantity for investigation. The only attempt to hydrolyse the compound which has succeeded was performed by heating it with concentrated hydrobromic acid (d 1.47) in a sealed tube during 6 hours a t 170'.A large yield of a substance was obtained, which proved t o be $-lutidostyril, or 2 : 4-di- methyl-6-hydroxypyridine, a substance first described by Hantzsch (Bey., 1884, 17, 2904), derivatives of which have frequently been ob- tained by the interaction of ethyl acetoacetate or its derivatives and ammonia (Gaxxetta, 1886, 16, 449 ; Annulen, 1890, 259, 169 ; Trans., 1895, 67, 220; 1897, 71, 299, &c,). It will be seen that the formula of +-lutidostyril, C7H,0N, may be derived from that of the original substance, C,H,ON,, by displacing CN by H, and that the latter may be regarded as a cyano-$-lutidostyril. This was confirmed by the detection of carbon dioxide and ammonia as bye-products of the interaction, which may be expressed as follows: C,HN(CH,),(OH)*CN + 3H,O + HBr = C,H,N(CH,),*OH + NH,Br + CO,.The slightly charred contents of the tube were extracted with water, filtered, and concentrated on the water-bath until the excess of acid was removed. On redissolving in a little water and adding soda until neutral, ammonia was freely evolved and the solution nearly solidified owing to the separation of a mass of long needles. These were filtered off and were found to be free from sodium and to melt a t 171-173". When heated in a test-tube, this product sublimed un- changed, the sublimate melting a t 176', and after recrystallisation a t 177-178' (179-180" corr.). It boiled at 303' (uncorr.). On adding excess of sodium hydroxide to its concentrated solution, a sodium derivative crystallised out in thin, lustrous plates.The substance is therefore Hantzsch's $-lutidostyril. This was further established by directly comparing the product with a specimen made by Collie's method (Trans., 1897, 71, 299). On bromination, it gave a product agreeing with Kerp's 3 : 5-dibromo-$- lutidostyril, but melting and decomposing at 253' (corr.) (Kerp gives 235'). 0.1058 gave 0.1405 AgBr. Br = 56.49. CH, C,H,ONBr, requires Br = 56.89 per cent. This substance is therefore Br/\;r CH,!N)OH104 MOIB : CYANOHYDROXYPYRIDINE DERIVATIVES On nitrating the $-lutidostyril, two compounds were obtained, one of which was Collie's 5-nitro-derivative melting at 254" (corr.) ; the other which crystallised in rosettes of short needles melting constantly at 196' (corr.), also gave numbers on analysis agreeing with those required for a mononitro compound, and was apparently a, mixture of Collie's 5-nitro- compound with the 3-nitro-compound (m.p. 260' corr.), which I have obtained in a different way (see p. 116). The sodium derivative of the product melting at 196' (corr.) was made, washed with ether, and analysed : 0.0650 gave 0.0234 Na,SO,. The free substance is therefore a nitro-$ -1utidostyril. I n the preliminary note (Proc., 1901, 17, 235), I described this incorrectly as 3-nitro-$-lutidostyril itself. Both compounds give, on reduction, the colour-reactions characteristic of 5-amino-$-lutidostyril (Collie, Trans., 1898, '73, 233). I f Holtzwart's compound be regarded as a cyano-$-lutidostyril, it must be represented by one or other of the two following formuh: Na = 11.68.C7H703N,Na requires Na = 12.1 2 per cent. and, curiously enough, its formation from 2 mols. of "isocgan- acetone " can be explained on either supposition, according as it is assumed that either methyl or hydroxyl wanders in the process. The following scheme will make this clear : H 7% QH3 C NC.Q+3 NC*FH \cH or CH~-C@*OH HO*C\N/C*CH,. (4. (B. 1 The compound represented by the formula (B) is already known, and has been prepared in a manner which loaves no doubt as to its constitution, namely, by condensing acetylacetone, ammonia, and cyanacetic ester (that is, acetylacetonamine and cyanacetamide),FROM DIACETONITRILE. 105 N C . C I ~ . 2 ' . ........... p 3 i I OiC CO \NHiH ............. W", ......................+ ,>cH -+ NH,! ..................... (Guaeschi, Atti R. Accad. Torino, 1892, 28, Centr., 1893, ii, 648; 1899, i, 289). As Guareschi's compound was stated to mine melted a t 293' (uncorr.), I found it *C*C@C\CH I I I HO*C\ /C*CH,. N 330; 1898, 34, 27; C%m. melt at 288-289', whilst necessary to prepare the former substance for comparison with my product. The two com- pounds exhibited a remarkably close resemblance, both physically and chemically, and careful comparison was necessary to determine that the tw.0 were in reality different ; indeed, it is only in their derivatives that the difference is a t all decided. Guareschi's compound forms longer and more lustrous needles than mine, although possessing similar sparing solubility in the usual sdvents and the same alkaloidal bitter taste.The melting point given in the literature is a cowected one ; hence the difference between the isomerides in this respect is twelve or thirteen degrees instead of four. [I found Guareschi's compound t o melt at 291' (corr.), whilst Holtzwart's melts at 305' (corr.). A mixture of the two melts between 270' and 275', but if this mixture be recrystallised, the product is quite different in appearance from either constituent, consisting of long, hair-like needles, which me I t a t 235--242O.I The only other physical property in which the crystals differ is their action on polarised light-Holtzwart's compound (m. p. 305') causing a uniform extinction at about 50' to the axis, whilst the crystals of Guareschi's isomeride (m. p. 291') frequently produce no effect, and when an extinction is observed it is confined to half the breadth of the needles and is nearly parallel to their axis.Chemically, too, Guareschi's compound resembles mine (1) in being non-basic ; (2) in affording metallic derivatives (which are, however, less soluble than those of my compound) ; (3) in giving +-lutidostyril, carbon dioxide, and ammonia when hydrolysed by fuming hydrobrornic acid, the cyanogen group being directly displaced by hydrogen just as in the case of the isomeride (p. 103) ; (4) in resisting the action of sodium hydroxide, sulphuric acid, methyl iodide, &c. This complete analogy between the two compounds leaves no doubt that both are cyano-J/-lutidostyrils, and as Holtzwart's compound is dzjTeTent from Guareschi's-which is 5-cyano-$-lutidostyril [formula (B)]-it can only have the constitution represented by formula (A),106 MOIR : CYANOHYDROXYPYRIDINE DERIVATIVES Such a compound should yield only mono-derivatives; this was actually found to be the case.Brornination of Holtxwart's Compound.-A nearly saturated solution of the substance in glacial acetic acid was mixed at 40' with a similar solution of an amount OF bromine just in excess of one molecular proportion. Action soon set in, crystals separating from the solution. The liquid was diluted to separate the part remaining in solution and the product was digested first with a warm dilute solution of potass- ium carbonate and then with a cold very dilute solution of sodium hydroxide. The slight residue insoluble in alkalis was recrystallised from boiling glacial acetic acid, from which it separated in minute prisms, nearly insoluble in other solvents, melting at about 270" (280' corr.), but decomposing, This substance contained 33.0 per cent.of bromine. The amount obtained was very small and insufficient t o determine its nature, On precipitating the alkaline solutions with acid, substances were obtained which ultimately proved to be identical, The major product was that extracted by sodium hydroxide ; this was purified by dis- solving it in the least possible quantity of a solution of sodium hydr- oxide and concentrating the liquid to the point of crystallisation. Long, white needles of a sodium derivative were thus obtained, easily soluble in water, and having a soapy feel.Before analysiug this substance, it was recrystallised. 0.2291 gave 0.1760 AgBr. C8H60N2BrNa requires Br = 32.08 per cent. To separate the parent substance, the solution was precipitated with acid ; the precipitate was well washed with boiling water, dried, and analysed, as it could not be recrystallised. It consisted of minute, white needles, which melted at 313' (327O corr.), but underwent decomposition. Br = 32-69. 0.1929 gave 0.160 AgBr. Br = 35.3. C8H70N2Br requires Br = 35.21 per cent. The amount of bromine found in the portion extracted by alkali There can be no doubt that the substance produced was the carbonate was 35.79 per cent. CH3 o-bromo-compound 7 CH,(~)OH~ CN"Br isomeric with the p-bromo-compound (m. p. 261') obtained by Guareschi.Nitration of EIbltawart's Compound.-This may be effected either with fuming nitric acid and with a mixture of this acid with strong sul-FROM DIACETONITRILE. 107 phuric acid. No change occurs below 50°, and a t a higher temperature the action tends to be violent. To complete the nitration, the solution was warmed on the water-bath during a few minutes, cooled, diluted with ice, and then supersaturated with sodium hydroxide. On stand- ing, a sparingly soluble sodium derivative of the nitro-compound crys- tallised out in orange rosettes. On recrystallisation, these formed long, yellow, lustrous needles, sparingly soluble in water, and quite distinct, therefore, from the salt of Collie's 5-nitro-+-lutidostyril- carboxylic acid (Trans., 1898, 73, 234). 0,2591 gave 0.0865 Na,SO,.The colour is doubtless due to isomerisation to the quinonoid nitroate Na= 10.80. C,H,03N3Na requires Na = 10.71 per cent. CH3 CH~\,):O NC":No*oNa, of which the white, nearly insoluble, free CH, substance is the $-acid, that is, On acidifying the solution of the salt, the nitro-compound was pre- cipitiated as a nearly white mass of needles, which melted at about 240°, but decomposed. After several recrystallisations from boiling water, it was obtained in long, opaque prisms which melted a t 253' (260' corr.). As the product resembled Collie's nitro-acid, I determined nitrogen in it ; although the nature of the substance prevented slow combus- tion, the result shows that the cyanogen group is intact. 0,1985 gave 37-2 C.C. moist nitrogen at 85' and 753 mm.N=22.59. C,H70,N, requires N = 2 1 *80 per cent. The potassium salt of this substance closely resembles the sodium salt, whereas the ammonium salt is deeper in shade, forming reddish- brown prisms melting a t 251' (corr.). A further quantity of the nitro-compound was obtained by evapor- ating the alkaline liquid, then acidifying, and extracting with alcohol. No other product could be isolated. An attempt to remove the cyanogen group with fuming hydro- bromic acid led only to the destruction of the substance. Nitration of Guamschi's Con&pound, C,H,ON,.-This was carried out as in the preceding experiment. The nitro-compound separates on diluting the acid in pale green, lance-shaped crystals. These melt at 261-263' and dissolve in a solution of potassium carbonate, forming108 MOIR : CYANOH YDROXYPYRIDINE DERIVATIVES an intensely yellow liquid, which, however, on evaporation, gives a white solid.To remove traces of a coloured impurity, the solid was washed with a little water; the white potassium salt was then redis- solved and the nitro-compound precipitated from the orange-yellow solu- tion by acid. After recrystallisation, it formed spear-like, oblique plates melting a t 263-264’ (272O corr.). The sodium and ammonium salts were also white in the solid state, but gave yellow solutions. The colour phenomena manifested by the two isomeric nitro-deriva- tives are obviously analogous to those given by 0- and p-nitrophenol respectively, to which they correspond in the relative arrangement of the nitro- and hydroxy-groups. On hydrolysing the nitro-compound by warming i t with fuming sulphuric acid a t looo, diluting, and boiling with a nitrite (Bouveault’s process), a new compound was obtained giving salts which were orange in the solid state.Its ammonium salt dissociates on drying. The best direct evidence of the position of the cyanogen group in Holtzwart’s componnd is afforded by the behaviour of the amino- compound formed on reducing its nitro-derivative. A solution of this substance gave very characteristic colour reactions, namely, (a) a cherry- red colour on aerial oxidation in presence of ammonia; (b) with ferric chloride, a green colour, darkening to a n intense indigo shade (very sensitive). Precisely similar changes were observed by Collie t o take place in the case of his 5-amino-$-lutidostyril and its carboxy-acid (Trans,, 1898, 73, 232).There can therefore be little doubt that Holtzwart’s compound is, as previously argued, the nitrile of Collie’s acid. To complete the series of reduction products, the nitro-derivative of The free substance melts a t 282” (corr.). CH, Guareschi’s compound-presumably &N -wasboiled withzinc CH,!~)OH and acid as before. The solution gave merely a dull brown shade with ferric chloride, and on adding ammonia an intense blue fluor- escence was developed, but no colour appeared in the liquid. Much time was unsuccessfully devoted to attempts to establish a direct connection between Holtzwart’s compound and Collie’s +-lutido- styril-3-carboxylic acid. The ester of this acid is obtained by condens- ing ethyl p-aminocrotonate under special conditions, an interaction in every way anaIogous to mine (Trans., 1897, 71, 299) ; I am greatly indebted to Dr.Collie for a specimen of this ester with which he provided me when, a,t first, I had some difficulty in preparing it. Attempts were made both to hydrolyse Holtzwart’s compound to Collie’s acid, and also to transform the latter into the former. AlthoughFROM DIACETONITRILE. 109 neither series gave positive resnlts, the experiments are of interest as exemplifying the stability of this class of compound. I n the first instance, a solution of the substance, in 80 per cent. alcohol, was boiled during fifteen hours with potassium hydroxide in large excess. The alcohol was then boiled off and a solution of ammonium carbonate added ; a copious cry stallisation of the unchanged substance took place.It was to be expected that if any carboxylic salt were formed i t would remain in solution; but on acidifying the filtrate only a faint turbidity was produced, and, as the expected acid (Trans., 1897, 71, 304) is practically insoluble in water, i t may safely be asserted that no hydrolysis whatever had occurred. This peculiar procedure mas neces- sitated by the fact that both the expected acid and its nitrile have the same melting point and general properties. I n addition to the methods already mentioned, heating with soda under pressure and also fusion with potash were tried; both pro- cesses, however, destroy Holtzwart’s compound completely, although it is attacked only a t a high temperature. Again, the action of warm fuming sulphuric acid (which hydrolyses Guareschi’s isomeride) was tried in vain, the substance being either unattacked, or sulphonated t o a minute extent.The inverse experiments are of greater interest, as throwing light on the probable cause of the resistance to hydrolysis of the nitrile group in Holtzwart’s compound ; for the same inertness is shown, in a lower degree, by the carbethoxyl group in Collie’s ester (m. p. 137’), and this is doubtless the cause of the failure of my efforts to synthesise the corresponding nitrile. I n the first experiment, the ester was heated with excess of strong ammonia during five hours at 155-160’; prac- tically no action occurred, the only new product being a very small quan- t i t y of the ammonium salt of Collie’s acid.This is very soluble in water. No trace of an amide was observed. Similarly, the ester was quite unaffected when heated with excess of zinc-chloride-ammonia. This agent also did not act on the corresponding ethyl 6-chlorolutidinecarb- oxylate obtained by Collie by the action of phosphorus pentachloride on his ester (Trans., 1898, 73, 589). I n the remaining experiments, I started with the acid (melting at 300° corr.). I n preparing it, time can be saved by fusing the ester with potash; quite a high temperature is necessary, but the yield of acid is good, as it completely precipitated on acidifying the solution of the product. The dry ammonium salt of the acid was first heated with excess of phosphoric oxide a t 300’, but on extraction with water, no trace of Holtzwart’s compound was left.On heating the ammonium salt alone, it decomposed smoothly a t its melting point (about 270O) into +-lutidostyril, carbon dioxide, and ammonia. In a final experiment, the acid was heated with 2 mols. of phosphorus pent.achloride, and after110 MOIR : CYANOHY DROXY PYRI DINE DERIVATIVE8 removing the oxychloride the residue was heated with excess of solid ammonium carbonate. On working up the product, a small quantity of sparingly soluble needles mas separated ; these, however, contained chlorine and were not investigated. These experiments exemplify the ‘( protective influence ” of the two o-methyl groups on every group which becomes imprisoned between them in the ring. Several cases in which this kind of protection is Br observed in benzene compounds, for example, /\CN, have been I IBr v 0% investigated by Sudborough and others.The cyanoxylene, /\CN j?OH, (Noyes, Amer. Chem. J., 1898, 20, 792), is a particularly close analogue of Holtzwart’s compound. There remain to be mentioned two points in which my experience has differed from Holtzwart’s; the first has reference to the bye- products formed in preparing the substance C,H,ON, from diaceto- nitrile, and the second to the action of phosphorus pentachloride on this compound. By treating the distillate obtained in preparing his compound with phenylhydrazine acetate, Holtzwart claims to have obtained cyanacetonephenylhydrazone. I was unable to confirm this observation, but as the liquid in the flask gives the hydrazone copiously, it is possible that in Holtzwart’s case some of this liquid may have come over mechanically with the ammonia.I n any case, the litera- ture on cyanacetone is in a state of confusion, there being no less than four claimants for the name. Of these, (I) that described by Glutz (J. pr. Chem., 1870, [ii], 1, 141) seems to be crude$-lutidostyril; (2) Bender’s sparingly soluble, beautifully crystalline compound, may be Holtzwart’s C,H,ON, (Ber., 1871,4, 518), whilst the oils and syrups obtained by Matthews and Hodgkinson (Ber., 1882, 15, 2679), and by James (Annulen, 1885, 231, 245), seem to be polymerides of the true cyanacetone of Holtzwart, a substance whicb, however, seems to have hut a momentary existence. As to the action of phosphorus pentachloride on Holtxwart’s com- pound, the author states (Zoc.cit., 329) that the product is gummy, but that he isolated from it a substance melting a t 175’ and giving figures agreeing with those required for the formula C,H6N, [which Beilstein enters wrongly as C,H,N, (Handbuch, 3, 1455)l. I n an experiment with a pure preparation of the substance, I found it very difficult to cause any action to take place, but finally obtained a small quantity of glistening needles melting at 165-166”, but con- taining chlovine not removable by alkalis. This substance is probablyFROM DIACETONITRILE. 111 the corresponding 2-chlorolutidine derivative, ‘’ or CH,(N)Cl ’ C8H7N,C1, but the quantity obtained did not permit of an aaalysis being made, I tried to synthesise it by the Sandmeyer method from the corresponding amino-compound (see next part), but only obtained Holtzwart’s compound instead ; such abnormalities in the behaviour of 2-aminopyridines have been frequently observed. It is evident from Holtzwart’s description of this experiment that he must have used a crude material, and I think that his compound C,H,N, owes its formation to some impurity.I found, for example, that on boiling the crude compound with acetic anhydride, a small quantity of a new compound crystallising in plates melting at 155’ was obtainable, whereas the pure substance gave no trace of this product. 11. The non-existence of vm Meyer’s Isomeric C,H,ON,.” By acting on diacetonitrile in ethereal solution with acetyl chloride and then adding water, Holtzwart obtained a base of the formula C,H,N,, melting a t 222’ (J.pr. Chem., 1889, [ii], 39, 236). The same compound was obtained by several other workers in von Meyer’s laboratory by acting on diacetonitrile with a variety of reagents, such as ethyl chlorocarbonate, ethylene dibromide, alcoholic hydrogen chloride, &c., all of which act merely by removing ammonia from two mols. of diacetonitrile and inducing condensation ; thus, 2C,H,N, = C,H,N, + NH,. I have found that the best yield of this compound is obtained by simply heating diacetonitrile with zinc-chloride-ammonia unfil the mass solidifies; on dissolving in acid and supersaturating with soda, the new compound is precipitated and may be filtered off. By acting on this substance with nitrous acid, von Meyer obtained a product of the formula C,H,ON,, which may evidently be regarded as the corresponding hydroxy-compound ; thus, C,H7N,-NH, + HNO, = C,H7N,*OH + N, + H,O (J.pr. Chem., 1895, [ii], 52, 89). This compound is described by von Meyer as melting a t about 260’, and he pronounced it to be different from the compound of the same formula made by Holtzwart in his laboratory in 1889, the evidence for this statement being the apparent difference in their melting points and certain differences in solubility. I have repeated this work, and find that the two compounds are in reality identical. The solution of the compound C,H9N, in dilute sulphuric acid was treated with a slight excess of nitrite and digested for some time at 30-40°, as it diaaotises with some difficulty.On112 MOIR : CYANOHYDROXYPYRIDINE DERIVATIVES boiling the solution, nitrogen was evolved ; the compound C,H,ON,, being non-basic, crystallised out on cooling, and after one crystallisa- tion from water, melted at 278-282O ; on recrystallising, the melting point was raised to 291-29Z0, and under the microscope the crystals were indistinguishable from those of Holtzwart’s compound. The melting point was not depressed by mixing the two. To confirm this result, the product was nitrated by the method described on page 107, and gave the golden needles of the sodium ‘ salt ’ of 5-nitro-3-cyano-$-lutidostyril there described. On reduction with zinc dust and sulphuric acid, the two colour reactions with ammonia and with ferric chloride were obtained.I n all these particulars, von Meyer’s product agrees with Holtzwart’s compound and no doubt can remain as to their identity. It is curious that von Meyer, having both substances at his disposal, should have been led to consider them different ; yet if is evident, judging from their melting points, that his specimens must have been very impure, and hence misleading data as to solubility, &c., were given by them. isomeric C,H,ON, I’ (Beilstein, Handbuch, 4, 1151) is thus 3-cyano-$-lutidostyril, and as it is obtained by the diazo-reaction from the compound C,H,N,, the latter must be 3-cyano-6-amino-2 : 4-lut- idine and its formation by the direct condensation of diacetonitrile may be expressed as follows : Von Meyer’s 3-Cyano-2 : 4-dimethyl-6-aminopyridine, From these data, probable constitutions can be assigned to the obscure compounds obtained by von Meyer’s students from diaceto- nitrile with various agents.Thus, the compound C,H,,ON, (m. p. 1 4 5 O ) , from cyanamide, which on boiling loses carbon dioxide and C,H,N3 (m. p. 222”). CHQ NC/\” ammonia, leaving Holtzwart’s C,H,ON,, must be UH,( )NH.CO.NH,, N and one of the compounds C,H,,N,, from hydrazine, must be CH, NC/\ CH,! JNH.NH; N113 FROM DIACETONITRTLE. 111. ~-Lutidostyril-5-car~ox~~~c Acid und some of its Derivatives. As already mentioned, every attempt to hydrolyse Holtzwart’s C,H,ON, (3-~yano-+-lutidostyril) to the corresponding acid has failed. On the other hand, I have succeeded in obtaining from Guareschi’s isomeride (5-cyano-q-lutidostyril) the corresponding amide and acid, I may, however, first describe a number of experiments instituted to ascertain the mechanism of Guareschi’s interaction, which is character- ised by the ease with which it takes place without a condensing agent.The interacting substances are ethyl cyanacetate and P-diketones, in the presence of a primary amine, and the reaction has been realised by its discoverer in a large number of cases (Atti R. Accud. Torino, 1893, 28, 330, 836; 1898, 34, 24; see also 1900, 36, 645). Of these, the simplest is that leading to the compound C,H,ON, (m. p. 2 8 9 O corr.) from acetylacetone, ethyl cyanacetate, and ammonia ; but since the first two substances are both acted on by ammonia, forming respectively acetylacetonamine, CH,*C(NH,):CH*CO*CH,, and cyan- acetamide, NC*CH,*CO*NH,, these must be considered the true inter- acting compounds.I found, in fact, that when the ammonia acts beforehand on only one of the substances, the condensation does not occur ; that is, mixtures respectively of acetylacetone with cyanacet- amide, or of acetylacetonamine with ethyl cyanacetate, do not con- dense ; whereas, if acetylacetonamine and cyanacetamide are pre- viously prepared free from ammonia, then the condensation occurs on mixing their aqueous solutions and gently warming. Now there are two possible explanations of this interaction, CH,.C~;o .................... c.3.c.. ....................... ........................ , .......................... / I H,N! \ H,’C*CN CH + co or CH + C * OH, \ \\ ,........................ // \\ i ........................ // CH,*C*INH * ......... 2 ............... H*jNH CH,*C* iNH, I. H/C*CN ....................... of which only the former is a Lc methylene condensation.” To decide between them, the experiment of heating acetylacetonamine with cyan- acetmethylamide was performed. The sole product was the N-methyl- derivative of Guareschi’s compound, C,H,ON,, and it appear sto me that its formation is not explicable by the second of the two schemes, as in this case there is no amino-group free from which water can be formed with the adjacent carboxyl group. This condensation, therefore, occurs as follows : .......................... CH,*C:O H,;C*CN CH3 . /\CX / .......................... \\ ...................... / I C H,*C* i ‘N ........H 2 ............ HiN __: \ + CH,(”J:O CH + co *CH, CH3 VOL. LXXXI.114 MOIR : CYANOHYDROXYPYRIDINE DERIVATIVES On the other hand, when the methyl group is introduced into the other constituent of the reaction, that is, when acetylacetone-methyl- amine is heated with cyanacetamide, the sole product is Guareschi's compound C,H,ON,, and not its N-methyl derivative. In this case, methylamine, and not ammonia, is eliminated, and in both cases the amine originally attached to the acetylacetone is the one which is expelled when the condensation takes place, the present reaction being expressed as follows : CH,, ~ . ~ . ............................ CH3 ............... H,IC*CN /\CN / ,.................. \\ ,. ................................ / CHQIH \ CH + co -+- CH,*C*iNHCH, HiNH .................................8 Another experiment had the object of ascertaining whether the acid- ifying influence of the cyanogen group is the determining factor in such condensations, and this was found to be the case, for when malonamide was substituted for cyanacetamide, no condensation with acetyl- acetonamine could be induced, although the only variation is the sub- stitution for the active CN group of the CO*NH, group. The methods of hydrolysis which proved successful with Guareschi's compound were: (1) fusion with potash; (2) treatment with warm fuming sulphuric acid. As both processes gave the same products, I shall confine myself to the latter one, which gives a good yield. I f the solution of Guareschi's compound in the acid (10 per cent, SO,) be diluted after standing for some time at the ordinary temperature, only unchanged substance separates ; if, however, the solution has been warmed a t 100' for a short time, nothing separates on dilution, but after several days a copious crystallisation of rosettes of needles is obtained. These are sparingly soluble in water, melt at 2 0 9 O OH9 (215'corr.), and consist of the sulphate of the amide, cE),N)OH &Om€, , .they are not affected by acetic anhydride, and when treated with ammonia or boiled with solution of potassium carbonate give the amide which melts a t 220-221' (22'7' corr.), is quite easily soluble in water, and appears to be dimorphous, forming at first hard granules, which on recrystallisation give small, flat needles with square ends.Like the other substances of this class, i t is easily soluble in caustic alkalis, forming a phenolic ' salt' crystallising in plates ; even on boiling with potassium hydroxide, hydrolysis of the amide to the acid is slow, as is also shown by its occurrence in the potash fusion. Unlike the original product, the amide acetylates readily, and, curiously enough,FROM DIACETONITRILE. 115 the product after recrystallisation is so like Guareschi's compound, C,H,ON,, that at first I thought it had been regenerated by the de- hydrating nction of the reagent. It forms long, white needles melting without darkening at 279-280° (290O corr.). That this substance is different from the two compounds of the formula C,H,ON, was proved by the method of mixed melting points and also by an analysis which CHQ /\CO *NH* CO*CH3 gave results agreeing with the formula CH) IOH \" 0.1075 gave 13.0 C.C.moist nitrogen at 1 8 O and 756 mm. N = 13-89. C,,H,,0,N2 requires N = 13.49 per cent. It is remarkable that the amide should be so basic as to form stable salts and an acetyl derivative, and for this that it might be an amino-acid, namely, /\ CH,! ,OH IcooNH2, and to decide this point N reason I at one time thought CH, CHAN,NH2 'xco2H, instead of tried a number of experi- ments, such as the isonitrile test and the action of nitrous acid followed by alkaline P-naphthol. The results were negative and the second formula was then definitely proved by conversion of the substance, by means of bromine and soda, into Collie's 5-amino-~-lutidostyril, CH, / ) N R 2 , which gives extremely characteristic colour reactions CH3(N,OH (see page 108, and Trans., 1898, 73, 232).The substance (m. p. 227') is therefore really the amide of $-Zutido- styriZ-5-carboxytic acid. As the hydrolysis of the amide is effected only slowly by acids or alkalis, I tried the action of nitrous acid. On boiling the solution, nitrogen was evolved and the carboxylic acid-which is very sparingly soluble- was precipitated. This acid forms needles closely resembling its iso- meride (Collie's +-lutidostyril-3-carboxylic acid, m. p. 300-304°), but melts at 244O (252' corr.), and, like its isomeride, decomposes into +lutidostyril and carbon dioxide when heated above its melting point. Potassium Sak of +--LutidostyriZ-5-carboxylic Acid, m.p. 252O (corr).-This was prepared by adding a solution of potassium carbonate to the acid, evaporating to dryness, and crystalIising from boiling alcohol. The next step was to obtain this acid. It forms long, flat needles and was dried at 120'. I 2116 CYANOHYDHOXYPYRIDIN E DERIVATIVES. 0.1564 gave 0.0668 K,SO,. C,H,O,NK requires K = 19.06 per cent. 3-Nitro-~-Iutidost~ri~.-In preparing this compound, T followed Collie's description of the processes used in producing 5-nitr+$-lutidostyril (Trans., 1898,73,231). On nitrating the acid melting at 244') I obtained 3-~itro-~~lutidostyril-5-cur~oxylic acid in the form of white, sparingly soluble needles melting at 225-227' (corr,), and giving intensely orange salts. On reduction in acid solution, the solution gave the same brown coloration with ferric chloride as its nitrile (the amino- derivative of Guareschi's compound, see p.108) gives. On heating the above nitro-acid at 260' until the evolution of carbon dioxide ceases, it is transformed into 3-nitro-$-Iutidostyr~l, which on recrystallisation forms pale, shining leaflets moderately soluble in water and melting at 260' (corr.), and on reduction gives a reddish- brown coloration with ferric chloride. The analogy with Collie's work in this field is brought out by the following scheme : K= 19.18. CH, CH3 OH3 CO,H/\ CO,H/\ NO, /\NO, cH,!~)oH -+ cH,!N!oH -+ CH,!~)OH Collie's acid, 5-Nitro-~-lutidostyril- 5-Nitro-+-lutido- m. p. 300-304" (corr.). 3-carboxylic acid. styril. CH3 CH, CH3 /\CO,H NO,f)CO,H CH,!~)OH CH3\N,0H New acid, 3-Nitro-+-lutidostyril- 3-Nitro-+-lutido. m. p. 252" (corr.). 5-carboxylic acid. styril. The Fwmation of $-Lutidost ril from Ethyl Acetoacetate. Duisberg (Annalen, 1882, 213, 174)) by heating ethyl acetoacetate with excess of ammonia, evaporating, and heating the resulting gum at 80°, obtained a compound decomposing a t about 280' and event- ually giving figures approximating to those required for the formula C,H,ON,. Thinking that this might be Holtzwart's compound, I tried to obtain it by heating ethyl acetoacetate with an equal bulk of strong ammonia in a sealed tube during 2 hours at 150'. The product was an oil con- taining crystals, but the latter were merely ammonium carbonate. On evaporating the thick filtrate from these, a brown gum was left which was kept on the water-bath for some time and then boiled with water and excess of animal charcoal. On concentrating the pale filtrate, ITHE DETERMINATION OF AVAILABLE PLANT FOOD IN SOILS. 117 obtained crystals which, after purification by repeated crystallieation from water, melted at 173-175O (177-179° corr.), and behaved in all respects as +-ZutidostyriZ. This had evidently been formed from isodehydracetic acid, the first stage in the condensation of ethyl acetoacetate. CH,. ~'joH---.-Etio-c-o;~~K CH,*C-CH ) .............................. CH,* 8-p QH , + Y*CH,+ QH Y-CH, --t VH !*OH, ........................... CO*[OEt H\C' GO-0 GO--N ,...... .................... , Ethyl acetoacetate. -+ " isoDeliydracetic acid." 3 +-Lutidostyril. CHEMICAL DEPARTMENT, CENTRAL TECHNICAL COLLEGE, LONDON, S. W.