LXXVI 1.-Experiments on the So-Called Migration of Atoms and Groups

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1078 ROBINSON : EXPERIMENTS ON THE SO-CALLED

LXXVI 1.-Experiments on the So-called Migration of Atoms and Groups. Pwt I. The Nityation of p-Iodoanisole and other lodo-Phenolic Ethew. By GERTRUDEMAUD ROBINSON.

THE circumstances attending the niigration of atoms and groups in chemical reactions or isomeric change1 are still but; little under- stood, and it does not at present seem to be possible to include all such transformations in a single geaeralisation. In certain cases, such as the Beckmann rearrangement and the pinacone- pinacolin change, there appears to be no loophole of escape from the theory of the wadering atom, but it is quite possible that this is due to our limited knowledge of the possible intermediate stages. Orton and Jones (T., 1909, 95, 1456) have shown that the migration of chlorine from side-chain to nacleus observed when N-chloro- acetanilides are treated with hydrochloric acid is due to the forma- Published on 01 January 1916. Downloaded by Temple University 25/10/2014 19:21:07. tion of an acetanilidel and chlorine, which interact with the formation of the end-product substituted in the nucleus together with regenerated hydrochloric acid. The clear proof, based on a study of the dynamics of the reactions involved, is convincing, and it is natural to group analogous reactions as also due to' the interven- tion of intermediate stages, but it is not easy to realise the conditions in every case under which these phases may be studied. The present investigation has been undertaken in the hope that it4will prove possible to apply the theory of successive reactions, the rational explanation of migration, to a number of transformations which at present do not appear to be capable of such elucidation. A large number of examples of migration of halogen atoms from one position +,o another in the aromatic nucleus have been noted, mid the majority of these occur during the nitration or lialogena- tion of phenols, and usually these changes may be readily explained View Article Online

MIGRATION OF ATOMS AND GROUPS. PART I. 1079

by the displacement of the halogen by the entering group and the re-entry by substitution in the new position. A curious reaction of this type was discovered by Reverdin (Ber., 1896, 29, 1003), who found that on nitrating piodoanisole the nitro-group displaces the iodine atom, which is apparently moved round to the ortho- position with respect to the methoxyl group. The difficulty presented by this example is that the further substitution of the pnitroanisole, which may be assumed to be the initial product of ths reaction, by the iodine also obtained, is, on the surface, improbable because pnitroanisole is not very readily converted into derivatives by further substitution and, further, iodine is well known to be a somewhat inactive agent. However, experiment showed that iodine does react with p-nitroanisole in nitric acid solution with the formation of the iodo-pnitroanisole obtained in the Reverdin transformation. It was also found that o-nitroanisole is changed by iodine in nitric acid solution to p-iodo-o-nitroanisole. As regards the first phase of the reaction the behaviour of iodo-pheaolic ethers with nitric acid has been examined, and itl is found that the normal reaction is the1 displacement of an iodine atom in the ortho- or para-position with respect to methoxyl with the formation of free iodine and a nitro-derivative. Thus 4 : 5-di-iodoveratrole (I) is changed successively to nitroiodoveratrole (11) and 4 : 5-dinitroveratrole (111), and 2 : 5-di-iodoquinol dimethyl ether exhibits a similar behaviour. 3-Iodo-6-nithro-ptolylmethyl ether (IV) yields 3 : 6-dinitro-ptolyl methyl ether (V), butl in this case a by-product was found in 2 : 3 : 6-trinitro-5-hydroxy-ptolyl methyl e'ther (VI) :

MeO/'\I MeO(\I MeO/\NO, Me01 Met ,,!FJ02 M~o!,/No, Published on 01 January 1916. Downloaded by Temple University 25/10/2014 19:21:07. \/11 (1.1 (11.) (111.) NO2 Me/\I MeOf\NO, Me{\OH NO,!,,!OM~ NO,\joMe NO,,,OMe NO2 (IV.1 (V.) tvr.1 In other cases which have been examined the displacement of iodine is accompanied by further nitration or oxidation. It was not found possible to isolate p-nitroanisole from the interaction of p-iodoanisole and nitric acid, since conditions where the displacement was possible also favoured iodination or further nitration. In considering the actual details of the mechanism of the reaction it is necessary, in the first place, to remember that the iodine is View Article Online

1080 RORTNSON : EXPERIMENTS ON THE SO-CATALED

probab,Iy relmoveld from the nucleus in the form of hypoiodous acid, as shown in the scheme: OH OMe OM9 \/ OMe

This then decomposes with the formation of iodine and iodic acid, and the latter sub8tance was proved to be one of the products obtained when 4 :5-di-iodoveratrole was treated with cold nitric acid (D 1.42). It is possible, but not, in the author’s opinion, very probable, that hypoiodous acid is the iodinating agent in the transformation, but it should be noted that iodine is observed to separate as such during the reaction, and this, acting on the1 nitroanisole, will produce a certain amount of hydrogen iodide which, in its turn, would be oxidised by any hypoiodous acid present. The following stages seen?, therefore, to represent the more reasonable view of the process: OMe OMe /\ /‘\ 1 +HNO, + i 1 +HOI HOT+HI -+ I,+H20 \/ \/ I NO, OMe OMe Published on 01 January 1916. Downloaded by Temple University 25/10/2014 19:21:07.

(Scheme A.) Although this process must occur to some extent, it is the author’s opinion that the major proportion of the iodonitroanisole results from a process of iodination of the piodoanisole to di-iodoanisole, followed by displacement of the para-iodine atom and formation of o-iodo-pnitroanisole. Di-iodoanisole can actually be isolated as an intermediate product of the reaction, and by further treatment with nitric acid is changed to the iodonitroanisole melting at 96’. These processes are represented in scheme B: OMe OMe ON e /’\ produced in initial /‘I HNOR , -++I’ stage of A) -+ \/ ( ’ \/’ \/ I I K 0, Scheme B.) View Article Online

MIGRATION OF ATOMS AND GROUPS. PART I. 1081

The remarks made in connexion with A relative to the displace- riieiit of iiitroxyl and the substitution by means of iodine or hypoiodous acid apply also to tlie similar reactions in B. The substituting action of iodine is not observed unless the nitric acid is of a sufficient concentration, and this consideration explains the limited scope of the transformation, since a rather peculiar state of affairs must be reached. The substance dissolved in the nitric acid must have a strongly positive group, since otherwise the iodine will not be displaced; and the product must not be nitrated further at tlie concentration of acid employed, but must be capable of iodination. Even with a subst(ance so closely allied to p-iodoanisole as the corresponding o-cresol derivative the further nitration to a dinitro-compound occurs with inconvenient rapidity? and in order to observe the rearrangement it was found necessary to operate with great care. The reactions involved in this example are represented as follows :

(4 OMe

\/' NO2

Published on 01 January 1916. Downloaded by Temple University 25/10/2014 19:21:07. Other cases of migration of halogen atoms in phenols and their ethers will readily conform to the scheme of successive reactions and have in most cases been so represented, but Robertson and Briscoe (T., 1912, 107, 1965), who have investigated transformations of this type especially arnong thymol derivatives, hold the contrary view. In certain eaamples of nitration of halogenated phenols, chlorine and bromine are displaced by nitsosyl, but remain in the molecule in a different position, whereas iodine is removed in the elementary condition, and it is supposed that the iodine is too heavy to reach the' goal when it is displaced from its position. It seems equally reasonable to assume that the iodine, once separated, does not re-enter the molecule because its reactivity is insufficient to effect the1 necessary substitution. The views of Robertson and Briscoe are founded on those of Auwers, who has very generally assumed the fact of the inigratioii of atoms and groups, basing his speculations on a considerable x x*:'" View Article Online

1082 ROBINSON : EXPERIMENTS ON THE SO-CALLED

series of experimental researches which cannot well be criticised en masse. Wanderings have been assumed to occur both to the adjacent carbon atom and to the next but one, and perhaps the theoretical difficulty presented by the assumption of a true leap may be somewhat less in the former than in the latter examples. The changes of the first class can very often be explained by an application of Thiele's theory of addition to conjugated systems, as shown below for the transformation of tribromo-+-quinol into tetrabromo-p-cresol under the influence of hydrobromic acid (Auwers and Dallwig, Ber., 1902, 35, 464) : OH Me OH Me \\/ H\/ Me H/'Br +HBr + Br/'\Br + Br."Br . BA' IIBr Rr jl~r B~ ~r \/ \/ () 0 OH OH As an example of migration to the next but one carbon atom the nitration of dibromo-pcresol may be quoted, and this is the actual case which Robertson and Briscoe (Zoc. cit.) mention in support of their hypothmis. The experimental evidence adduced by Auwers (Ber., 1902, 35, 357) in support, of his contention that the reaction should be represented as shown below seems far from conclusive. The1 action of nitric acid on dibromo-pcresol yields an intermediate hemi-pquinone (VII), and under the influence of reagents the nitro-group is supposed to wander to the ortho-position, dis- placing the bromine atom: Me NO, Me \ /" Me Me Published on 01 January 1916. Downloaded by Temple University 25/10/2014 19:21:07. /\ HNOj /\. /\ /\

Brl 'Br -* BJI 'IBr * Bi()NO, f- BI!l \/' \/ \/ NO, OH OH II A 0 (VII.) (VIII.) Rowever, this hemiquinone (VII), the constitution of which is the key to the solution of the problem, does not undergo simple reactions resulting in a high yield of product, and has none'of the characteristics of a pure subst'ance. It melts over a range of temperature, and its unstable character is emphasised in the descrip- tion. As likely as not, it contains the isomeric hemi-o-quinone (VIII), and probably the proportion of this in the product could be judged by the amount of bromonitrocresol obtained when the mixture is treated with alkali solutions. Both (VII) and (VIII) represent anhydrides of the initial product of addition of nitric acid View Article Online

MIGRATION O$ ATOMS AND GROUPS. PART I. 1083

to dibromop-cresol, and it is probable that an equilibrium is reached in neutral or acid solutions. Such considerations can account for the results obtained by Auwers and others in examin- ing the nitration of phenols without the improbable assumption of the wandering of atoms or groups.

EXPERIMENTAL. 2-~odo-4-nitroutiisole.

The formation of this substance by the nitration of both 0- and 21-iodoanisole as described by Reverdin (loc. cit.) was confirmed, and in carrying out the reaction in the iatter case, the separation of iodine was observed. The substance may also be obtained by the iodination of pnitroanisole in nitric acid solution. pNitroanisole (1 gram) was mixed with nitric acid (2 c.c., D 1.4) and powdered iodine (1.3 grams, 1.5 mols.). After allowing to1 remain overnight at the ordinary t'emperature, water was added, the excess of iodine removed by sulphurous acid, and the solid collected and crystallised from alcohol. The colourless needles melted at 96O, and the melting point was not lowered when a specimen was mixed with 2-iodo-4-nitroanisole obtained by either of Reverdin's methods. This investigator obtained a substance melting at 73O by the nitration of p-iodoanisole under certain conditions, and to this he ascribed the constitution of the substance described in the next section. However, this material, melting at 73O, has been obtained and examined by the present author, and appears to be a mixture of 2-iodo-4-nitroanisole with either pnitroanisole or more probably di-iodoanisole. The) mixture is changed by nitric acid and iodine

Published on 01 January 1916. Downloaded by Temple University 25/10/2014 19:21:07. to pure 2-iodo-4-nitroanisole, melting at 96O. Many attempts, all unsuccessful, were made to isolate p-nitroanisole from the products obtained when nitric acid reacts with piodoanisole, but, on the other hand, the1 intermediate formation of di-iodoanisole was recog- nised. Nitric acid (D 1.5, 1 c.c.) was cooled in ice and piodoanisole (0.5 gram) added in onel portion. The mixture was immediately flooded with water, neutralised, and distilled in a current of steam. The solidified oil was collected, crystallised from aqueous ethyl alcohol, and the substance obtained in colourless prisms melting at 68O alone or mixed with 2 : 4-di-iodoanisole. When this substance is treated with nitric acid the iodine in the pposition is displaced by nitroxyl, and the iodonitroanisole melting at 96O obtained along with free iodine.

x x*" 2 View Article Online

1084 ROBINSON : EXPERIMENTS ON THE SO-CALLED

NO,

This substance was readily produced from o-nitroanisole exactly as described above for the iodination of pnitroanisole. The substance cryst'allised from alcohol or acetic acid in pale yellow prisms melting at 98O. It may bet distinguished from its isomeride, the subject of the last section, by its yellow colour. A mixture of the two compounds showed a depressed melting point: 0.1482 gave 0.1653 CO, and 0.0260 H,O. C=30*4; H=1*9. C,H,O,NI requires C = 30.2 ; H = 2.1 per cent. The constitution of this substance is proved by its conversion, on treatment with fuming nitric acid, into 2 :4-dinitroanisole melting at 88O (mixed melting point), and iodine, and also by the following transformation into 2 : 4-di-io-doanisole. The iodonitroanisole (3 grams) was reduced at the ordinary temperature during twelve hours by tin (3 grams) and concentrated hydrochloric acid (10 c.c.). The base was isolated by extraction with ether after the addition of sodium hydroxide and crystallised from alcohol in colourless plates melting at 87O. It was dissolved in dilute sulphuric acid, carefully diazotised, and the solution then added to an excess of an aqueous solution of potassium iodide. The product was dissolved in ether, freed from iodine by sulphurous acid, and crystallised from alcohol. The colourless prisms melted at 68-69O, and were identified as 2 : 4-di-iodoanisole (mixed melting point).

OMe I Published on 01 January 1916. Downloaded by Temple University 25/10/2014 19:21:07.

3-Nitro-o-tolyl methyl ether was obtained from the corresponding nitrocresol by a process of methylation which may successfully be applied for the preparation of the methyl ethers of mono-, di-, and even tri-nitrophenols. Thel ethers required for the present investigation were all prepared in this way, and in all cases with excellent results. The nitrophenol is heated in an oil-bath in boiling xylene solution with rather more than a molecular proportion of methyl sulphate and an excess of potassium carbonate. The reaction is finished when the red potassium salt has given place to colourless potassium sulphate and potassium methyl sulphate. The xylene is then removed by distillation in a current of steam. In certain cases, for example, in the methylation of picric acid, it is desirable to use nitrobenzene in place of the xylene. 3-Nitro-o-tolyl methyl ether was reduced and the amine con- View Article Online

MIGRATION OF ATOMS AND GROUPS. PART I. 1085

verted by diazotisation and treatment with potassium iodide in the usual manner into 3-iodo-o-tolyl methyl ether, an oil boiling at 20O0/19 mm. : 0.1650 gave 0.1573 AgI. 1=51*5. C8H,01 requires I=51*2 per cent.

OMe 5-1odo-o-tolyl Methyl Ether, Me./-- '\. \--/ I The 5-amino-o-tolyl methyl ether required for the preparation of this substance1 crystallises from methyl alcohol in long, slender needles melting at 92-93O, whereas Hofmann and Miller (Ber., 1881, 14, 571) give 52-53O. Its acetyl derivative was prepared and crystallise'd from water or methyl alcohol in needles melting at 158'. The amine was converted into the corresponding diazonium sulphate, and the diazo-group then displaced by iodine in the usual manner. The 5-iodo-o-tolyl methyl ether was obtaineld in excellent yield. It crystallises from acetic acid in colourless plates melting at 79-80": 0.1366 gave 0.1938 CO, and 0.0506 H,O. C=38.7; H=4*1. C,H,OI requires C= 38.7 ; H -3.6 per cent.

OMe 1 .3-To~o-5-t~itro-o-to7?/1Meth?yl Ether, Me/'- \ \ ---/I NO2 A. 3-Iodo-o-tolyl methyl ether (1 gram) was mixed with nitric

Published on 01 January 1916. Downloaded by Temple University 25/10/2014 19:21:07. acid (4 grams, 0 1.4) and allowed to remain overnight. The solid precipitated by the addition of water was collected and crystallised from aqueous methyl alcohol and obtained in long, hair-like, colourless crystals melting at 83O and readily soluble in most organic solvents : 0.1559 gave' 0.1891 CO, and 0.0428 H,O. C=33.1; H=3.0. C,H,03NI requires C = 32.8 ; H = 2.7 per cent. B. The nitration of 5-iodo-o-tolyl methyl ether under the same conditions resulted in the separation of iodine and the production of .a relatively smaller yield of the nitro-derivative, which was always produced along with 3 : 5-dinitro-o-tolyl methyl ether, and separate'd by fractional crystallisation from aqueous methyl alcohol, and finally from methyl alcohol. A careful comparison and mixed melting-point determination showed that the product was identical with that described under A. C'. The combined action of nitric acid and iodine on 5-nitro-o- View Article Online

1086 ROBINSON : EXPERIMENTS ON THE SO-CALLED

tolyl methyl ether also resulted in t.he production of 3-iodo-5-nitro- o-tolyl methyl ether. The substance melted at 83O after cryst(a1- lisation and the melting point was not depressed when the substance was mixed with a specimen obtained from 3-iodo-o-tolyl methyl ether. When 3- or 5-nitro- or -iodo-o-tolyl methyl ether are treated with fuming nitric acid or heated with nitric acid, they all yield one and the same 3 :5-dinitro-o-tolyl methyl ether, which crystallises from aqueous alcohol in nearly colourless needles melting atl 71-72O. It may also be obtained by the nitration of o-tolyl methyl ether. The corresponding ethyl ether has been described by Stadel (AnizaZe?z, 1883, 217, 154), and this methoxy-derivative resembles it in yielding dinitrocresol, pale yellow needles melting at, 85O, on hydrolysis with a boiling solution of sodium hydroxide (20 per cent.), whilst on heating in a sealed tube at looo with ten times its weight of a mixture of equal volumee of methyl alcohol and aqueous ammonia (D 0.880) a sparingly soluble, yellow precipitate of 3 : 5-dinitro-o-toluidine was formed in three hours. The solid was collected and crystallised from acetic acid and obtained in yellow, prismatic needles melting at 214O. Stadel (R?z?znZcn, 1883, 217, 183) gives 208O and Bamberger and Seitz (Ber., 1897, 30, 1253) give 211O. This nitroamine remains unchanged in boiling acetic anhydride, but on the addition of a trace of sulphuric acid is rapidly acetylated with the formation of the colourless acetyl derivative which crystallises in needles and melts at 203O.

4 : 5-Di-iodoveratro!e ot2d 2 : 5-Ui-iodoqzcinol Dintethyl Ether. Thess substances have previously been prepared, the former by Published on 01 January 1916. Downloaded by Temple University 25/10/2014 19:21:07. Bruggemann (J. pr. Chem., 1896, [ii], 53, 252) and the latter by Kauffmmn and Fritz (Bw., 1908, 41, 4416), by the action of iodine and mercuric oxide on the corresponding phenolic ethers. The process is inconvenient and the yield poor, and in place of it the author has employed the following method : Veratrole or quinol dimethyl ether (15 grams) was mixed with acetic acid (20 c.c.) and a solution of iodine monochloride (26 grams) in acetic acid (20 c.c.) gradually added. After the initial reaction, accompanied by development of heat, had subsided, the mixture was heated on the steam-bath until no more hydrogen chloride was evolved. On cooling, colourless needles separated, and a further quantity could be obtained by the addition of water. The solid was collected and crystallised from alcohol containing sulphurous acid. Di-iodoveratrole melted at 132O (Bruggemann, Zoc. cit., gives 125O), and the quinol derivative at 171°, as described by the authors mentioned above. View Article Online

MIGRATION OF ATOMS AND GROUPS. PART I. 1087

4-Zodo-5-?zitroverntrole (Formula 11). Di-iodoveratrole (4 grams) was dissolved in acetic acid (125 c.c.) and nitric acid (40 c.c., D 1.4) gradually added. After fifteen minutes the product was precipitated by water and collected. It consisted of 4-iodo-5-nitroveratrole, which was obtained in almost theoretical amount. The substance was washed with sulphurous acid and wabr and crystallised from alcohol, in which it is sparingly soluble, in intense yellow needles melting at 151O: 0.1679 gave 0.1948 CO, and 0.0456 H,O. C=31*6; H=3*0. C,H,O,NI requires C= 31.1 ; H = 2.6 per cent. On further treatment with nitric acid (D 1.4, mixed with 10 per cent. of D 1.52) the remaining iodine was displaced by nitroxyl and 4 : 5-dinitroveratrole formed. The substance melted at 129O alone, or when mixed with 4 : 5-dinitroveratrole obtained by direct nitration of veratrole. I 2-Iodo-5-?zitropz~iiiolDimet hyl Ether, OMe4,' \OMe. \ -./ NO2 Di-iodoquinol dimethyl ether was dissolved in the minimum amount of cold acetic acid and an equal volume of nitric acid (U 1-42) added. After fifteen minutes the product was separated by the addition of water, and as in the previous example the reaction had proceeded in almost quantitative manner with the formation of an iodonitro-derivative. The solid was collected, washed with sulphurous acid, and crystalhed from alp ?hol, being so obtained in bright yellow needles melting at 152O: Published on 01 January 1916. Downloaded by Temple University 25/10/2014 19:21:07. 0.0954 gave 0.1114 CO, and 0.0252 H,O. C=31-8; H=2*9. C,H,O,NI requires C = 31.1 ; H = 2.6 per cent. When this substance is covered with fuming nitric acid and water immediately added, the second iodine atom is displaced and the substance after collection and crystallisation from alcohol melted at 200-2020 and at the same temperature when mixed with a specimen of undoubted 2 : 5-dinitroquinol dimethyl ether.

3 :3/-Di;odo-4 :4/-dimethox~di;D7tenylmethane, I I

o-Iocioanisole (1 gram) was mixed with sulphuric acid (8 grams of 80 per cent.) and an aqueous solution of formaldehyde (1.5 grams of 40 per ce'nt.) gradually added with cooling. Aftes remaining View Article Online

1088 ROBINSON : EXPERIMENTS ON THE SO-CALLED

overnight the mixture was added to water, the solid collected, and crystallised from acetic acid, being obtained in plates melting at 142O: 0.1530 gave 0.1478 AgI. 1=52.3. C,,H,,O,I, requires I = 52.9 per cent. The substance dissolves in concentrated sulphuric acid to a pale pink solution which becomes brown on warming. An alternative1 method of preparation is from 3 : 3'-dinitro-4 : 4'- dimethoxydiphenylmethane (D.R.-I?., 140690) by reduction with tin and hydrochloric acid, followed by tetrazotisation and displacement of the diazo-groups by iodine in the usual manner. The substance so obtained was identical with that described above. The substance is either unacted on by nitric acid or, under more vigorous conditions, is changed to 2 : 4-dinitroanisole; no intermediate products could be1 isolated.

3-Iodo-6-dro-p-tolyl Me thy1 Ether (Formula IV) . Nitro-p-craol was smootlily converted into its methyl ether by the process previously described (see p. 1084) and the methoxy- derivative reduced at 50° by means of tin and liydrocliloric acid. The amine isolated by distillation in a current of steam was crystal- lived from light petroleum (h. p. 60-70O) and obtained in feathery needles melting at 53-94O, whereas Hofmann and Miller (Ber., 1881, 14, 573) give 36-38O and Limpach (Ber., 1889, 22, 349) gives 51.5O. The acetyl derivative melts after crystallisation from alcohol at 107O (Limpach, Zoc. cit., gives llOo), and on nitration Published on 01 January 1916. Downloaded by Temple University 25/10/2014 19:21:07. yielded 6-nitro-3-acetylamino-p-tolyl methyl ether, yellow needles melting at 156" (Limpach, Ber., 1889, 22, 790). The nitroamine (15 grams), obtained by the hydrolysis of the acetyl derivative with concentrated hydrochloric acid and alcohol, was mixed with water (50 c.c.) and sulphuric acid (5 c.c.) and after cooling to Oo was gradually treated with sodium nitrite (2.1 grams) dissolved in water (25 c.c.). The yellow amine gradually passed into solution as the corresponding diazonium sulphate, and when the reaction appeared to be complete, the solution was filtered and added to potassium iodide (20 grams) dissolved in water (100 c.c.). The mixture was allowed to remain during a quarter of an hour, and the reaction then completed by warming on the steam-bath for a few minutes. Sulphurous acid was added to remove iodine, and the precipitate collected and crystallised from methyl alcohol, in which it is sparingly soluble in the cold. It was obtained in long, flat needles melting at 118O: View Article Online

MIGRATION OF ATOMS AND GROUPS. PART I. 1089

0.1141 gave 0.1355 CO, and 0.0314 H,O. C=32.4; H=3.0. C,H,O,NI requires C = 32.8 ; H = 2.7 per cent.

2 : 5-Dinitro-p-tolyl Methyl Ether (Formula V). The iodonitro-ptolyl metqliyl ether obtained as in the last section was mixed with three times its weight of fuming nitric acid, when the separation of iodine was observed. The solution was filtered through glass-wool and poured into water. The products were a neutral substance and a nitrophenol, and were separated by solution in ether and extraction of the latter by means of a 30 per cent. solution of potassium hydroxide. The bright red potassium salt separated in neemdles, and its examination is described later, whilst the ethereal solution was dried and the solvent removed by distillation. The crystalline residue was recryst'allised from alcohol and obtained in pale yellow needles melting at 126O: 0.1101 gave 0.1851 CO, and 0.0394 H,O. C=45.8; H=3*9. C,H,O,N, requires C = 45.3 ; H = 3.8 per cent. The relationship of this substance to the antecedent nitroamino- and iodonitro-compounds is shown by the following expesiment, which proves that a direct displacement of iodine by nitroxyl has occurred. When either this substance melting at 126O or 6-nitro- 3-amino-17-tolyl methyl ether was reduced by means of an excess of tin and hydrochloric acid and the resulting isolated base acetylated, the same diacetylamino-derivative was produced. The substance crystallised from alcohol, in which it is sparingly soluble, or froin acetic acid, in long, slender, colourless needles melting at 270° : 0.1131 gave 0.2543 CO, and 0.0712 H,O. C=61*3; H-7.0. Published on 01 January 1916. Downloaded by Temple University 25/10/2014 19:21:07. C,,H,,O,N, requires C= 61.0 ; H = 6.8 per cent.

2 : 3 : 6-Trl:i,itro-5-J~ydroll;'~-p-tol.~lMethyl Ether (Formula VI). The red potassium salt isolated as described above was dissolved in water and acidified with hydrochloric acid. The yellow, crystalline precipitate was found to be a mixture, and on crystallisation from aqueous alcohol and also from ether, the melting point gradually rose to 115O, when the substance appeared to be homogeneous. An analysis of a specimen of low melting point gave C=37.2, H = 3.9, which indicates that the main product, a trinitro-compound, is contaminated with a similar dinitro-derivative. The substance melting at 115O occurred in yellow, rectangular prisms which dissolved in water to a yellow solution which gave insoluble, bright yellow precipitates with solutions of alkaloids, such as riarcotine : View Article Online

1090 EXPERIMENTS ON MIGRATION OF ATOMS AND GROUPS.

0.1091 gave 0.1408 CO, and 0.0326 H,O. C=35*2; H=3*3. C,H,O,N, requires C = 35.1 ; H = 2.6 per cent'.

NO, OMe 2 : 5 : 6-Triirit~oli,omoverccf~ole,Me/' -'\OMe. \-/ No, NO, The pure1 trinitro-compound just described was methylated by methyl sulphate in xylene solution in the presence of potassium carbonate, and after removing the solvent' in a current of steam an oil remained which quickly solidified on cooling. It was collected and crystallised from aqueous methyl alcohol, and obtained in colourless needles melting at 73-74O: 0.1124 gave 0.1567 CO, and 0.0335 H,O. C=38*0; H=3.3. q,H,O,N, requires C= 37.6 ; H = 3.1 per cent. This substance remained unchanged when treated with a solution of nitric acid in sulphuric acid. It' was converted into an orange-yellow nitroamine on boiling with concentrated alcoholic ammonia, but the product was not further examined. Attempts were made to prepare this compound direct from homoveratrole or the known nitrohomoveratrole by further nitration, but without success, as the methyl group was always elimin- ated, probably by preliminary oxidation, followed by displacement of the formyl or carboxyl radicles produced. The result of nitration in sulphuric acid solution was always either 4 : 5-dinitroveratrole or, with more nitric acid, trinitroveratrole. Published on 01 January 1916. Downloaded by Temple University 25/10/2014 19:21:07.

This compoiind was prepared as a possible stepping-stone to the trinitrohomovelratrole. 6-Nitro-4-liydroxy-m-tolyl methyl ether (Cardwell and Robinson, T., 1915, 107, 255) was dissolved in just sufficient sulphuric acid and nitrated by the addition of a little more than a molecular proportion of potassium nitrate. After remaining during a minute, ice1 was added, and the precipitated dinitro-derivative collected and dried. It was then methylated as in previous examples, and after removal of the xyleae was dissolved in ether. The dried extract was evaporated, and the residue crystallised from aqueous methyl alcohol. The colourless needles so obtained melted at 120O: 0.0837 gave 0.1374 CO, and 0.0347 H,O. C =44.8 ; H =4*6, C,HI,O,N, requires C = 44.6 ; H- 4.1 per cent, View Article Online

EXPERIMENTS ON THE WALDEN INVERSION. PART 11'. 1091

Att'empts further to nitrate this substance were unsuccessful. On reduction aiid condensstion with phenanthraquinone a deep yellow plienaiitliraplieiiaziiie was obt'ained. This dissolves in benzene to a yellow solution, which exhibits weak green fluorescence, and in sulphuric acid to a dainson-red soltition.

UNTVERSITIESOF SYDNEY AND LTVERPOOL. [Received, September 13th, 1916.1 Published on 01 January 1916. Downloaded by Temple University 25/10/2014 19:21:07.