crystallises from alcohol, in which it is moderately soluble, in large, nearly colourless, very thin plates, and melts at 60 5°; on analysis: 0.1848 gave 0.2050 AgCl + AgBr. AgCl + AgBr = 110.9.

C13H12OCIBr requires AgCl + AgBr=1106 per cent.

Discussion of Results.

The results tabulated on pages 35-37 serve to show that a single halogen atom in position 1, contiguous to the hydroxyl group of B-naphthol, has a most remarkable effect in limiting etherification, the effect being least in the case of methyl and greatest in that of propyl alcohol. Chlorine has an even greater effect than bromine, and a nitro-group in position 1 entirely prevents etherification. That the position of the halogen is the main determining cause of its influence is clearly brought out by the fact that 3'-bromo-3-naphthol is etherified as easily as the unbrominated naphthol, but it will be seen that, on introducing bromine into position 3' in either 1-chloro- or 1-bromo-ẞ-naphthol, the production of ether is considerably diminished.

These results stand in striking contrast to those obtained in the well-known experiments made by Victor Meyer and Sudborough, since extended by others,* on the etherification of substituted benzoic acids. In the case of benzoic acid, a single group in the orthoposition has little influence, whereas two such groups, if they do not altogether prevent etherification (Cl, Br, I, NO), greatly affect either the rate at which it takes place or its extent (CH3, OH, F). Victor Meyer has sought to find an explanation of these facts in stereochemical considerations, and has regarded the influence exercised by various radicles as dependent on their volume; but, strange to say, he has taken mass as the measure of volume.t

Such a hypothesis appears to be by no means justified by facts. Thus the order of inhibitive influence of different radicles on the formation of ethereal salts of ortho-substituted benzoic acids appears from Kellas' results to be Cl, CH, Br, I, NO2 ; but the order of the relative weights is CH, Cl, NO2, Br, I, and that of atomic volumes, CH, Cl, Br, NO2, I (Graham-Otto, I, 3, 449), or according to Traube (Annalen, 1896, 290, 43) Cl = Br=I (13·2), CH, (19.2), NO2 (20). From Goldschmidt's values for the velocity coefficients, the radicles

* V. Meyer and Sudborough, Ber., 1891, 27, 510, 1580, 3146; Lepsius, ibid., 1635; V. Meyer, Ber., 1895, 28, 182, 1254, 2773, 3197; 1896, 29, 830, 1397; van Loon and V. Meyer, ibid., 839 ; Goldschmidt, Ber., 1895, 28, 3218, Kellas, Zeit. physikal. Chem., 1897, 24, 221; Wegscheider, Monatsh., 1895, 16, 75; Ber., 1895,28, 1474, 2535; Monatsh., 1897, 18, 629; Sudborough and Feilmann, Proc., 1897, 13, 241.

For a discussion of this point, see V. Meyer, Ber., 1895, 28, 126; 1896, 29, 843; Wegscheider, Ber., 1895, 28, 126, Monatsh., 1897, 18, 635.

should stand, as regards retarding influence, in the order Br, CH, NO2, but in the case of the naphthyl ethers, the order appears from my results to be Br, Cl, NO. So that the observations of Goldschmidt and of Kellas, as well as my own, are in accord neither with the arrangement by atomic weights nor with that by atomic volumes; consequently, there appears to be a factor governing the etherification of both carboxylic acids and phenols of which we are at present in ignorance. Even if we consider, as Sudborough and Feilmann have suggested that the etherification is determined by two factors, (1) the stereochemical influence of the configuration, (ii) the strength of the acid as measured by its affinity constant, we are brought no nearer to an explanation of the extraordinarily great inhibiting influence of a nitro-group compared with that of other groups.†

Wegscheider (Monatsh., 1895, 16, 75, and 1897, 18, 629) has given reasons for considering that, in the etherification of carboxylic acids under the influence of alcohol and concentrated sulphuric acid or hydrogen chloride, an intermediate compound is formed by addition to the carboxyl group, as was originally assumed by Henry (Ber., 1877, 10, 2041), and later work has strengthened this hypothesis (compare Lloyd and Sudborough, Trans., 1899, 75, 580); he has suggested that phenols undergo etherification in a somewhat similar

Sudborough and Lloyd (Trans., 1899, 75, 467, 580) give a bibliography of papers dealing with the influence of ortho-substituted groups on the etherification of acids, the hydrolysis of ethereal salts, and of acid chlorides, amides, and nitriles ; the results obtained by Küster and Stallberg (Annalen, 1894, 278, 207) belong to the same category. Contiguous groups also exert an important influence on the preparation of oximes and phenylhydrazones of aromatic aldehydes and ketones (Kehrmann, Ber., 1888, 21, 3315; 1894, 27, 3344; J. pr. Chem., 1890, [ii], 40, 257; Hantzsch, Ber., 1890, 23, 2769; Feith and Davies, Ber., 1891, 24, 3546; Petrenko-Kritschenko, Ber., 1895, 28, 3203; Baum, Ber., 1895, 28, 3207, V. Meyer, Ber., 1896, 29, 830); the formation of imido-ethers from nitriles (Pinner, Ber., 1890, 28, 2917); and many other more complex interactions (compare Busch, J. pr. Chem., 1895, [ii], 51, 113; 52, 273; 1896, 53, 414; 1897, 55, 356; Jacobson, Annalen, 1895, 287, 118; 1898, 303, 290; Ber., 1898, 31, 890; Anschütz, Ber., 1897, 30, 221; Bischoff, Ber., 1897, 30, 2478, 2772; 1898, 31, 3024; Scholtz, Ber., 1898, 31, 414 and 627; 1899, 32, 2251; Wedekind, Ber., 1898, 31, 1746; Friedländer, Monatsh., 1898, 19, 627; Paal and Schilling, J. pr. Chem., 1896, [ii], 54, 277; Paal and Benker, Ber., 1899, 32, 1251; Paal and Härtel, ibid., 2057). The presence of ortho-alkyl groups in aromatic ketones and ketonic acids also determines very largely the behaviour of these compounds on hydrolysis (Louïse, Ann. Chim. Phys., [vi], 1885, 6, 206; Elbs, J. pr. Chem., [ii], 1887, 35, 465; V. Meyer, Ber., 1895, 28, 1270; Muhr, ibid., 3215, and Weiler, Ber., 1899, 32, 1908).

Victor Meyer, in discussing the atomic volume value, suggests "dass das Estergesetz uns ein Mittel in die Hand gebe dio relative Raumerfüllung der Atome in den organischen Verbindungen mit einander zu vergleichen." The varying inhibiting influence of the same element in acids and in phenols seems to preclude the acceptance of this suggestion.

manner, and that initially they give rise to keto-dihydro-derivatives (Monatsh., 1895, 16, 140). According to this view, ẞ-naphthol would be first converted into the compound

H2

OH
OEt,

and on losing water this would yield B-ethoxynaphthalene. Evidence to a certain extent in favour of this view may be found in the behaviour of B-naphthol in contrast with that of phenol. Experiments made by Mr. Panisset, at Dr. Armstrong's suggestion, show that phenol and parabromophenol may be partially etherified by means of alcohol and sulphuric acid, but that they yield at most about 25 per cent. of ether. Inasmuch as benzene and its derivatives are less prone to form additive compounds than are naphthalene and its derivatives, and the former are generally less readily attacked than the latter, the fact that phenol is less readily etherified than naphthol is in accordance with the view that addition precedes substitution (compare Armstrong, Trans., 1887, 51, 258; Armstrong and Rossiter, Proc., 1891, 7, 89). Now if benzene is represented by Kekulé's formula, it is a matter of indifference on which side of a CO2H group the double linking is placed, but it is not unlikely that, in bromobenzoic acid, for example, it is between the unbrominated carbon atoms, so that there is an active ethenoid linking in the immediate neighbourhood of the carboxyl. But it may well be that in B-naphthol no such shift can take place, and that when the linking between positions 1 and 2 is rendered comparatively inactive by the introduction of a radicle into position 1, the combining power of the compound is greatly reduced. Victor Meyer's observations on the etherification of 2-chloro- or 2-hydroxy-1-naphthoic acid and of 3-chloro- and 3-hydroxy2-naphthoic acid are equally in accordance with this view: the former are not attacked whilst the latter are readily etherified. There can be no doubt that 1-derivatives of 2-naphthoic acid will prove equally unsusceptible.

Although the structure of the nucleus has a distinct influence, it would appear that it is rather the specific attracting power of the radicle which is eventually etherified that becomes affected and diminished by the introduction of negative radicles into the nucleus in its neighbourhood. Armstrong, indeed, has suggested this in explanation of the phenomena observed by Victor Meyer, and has pointed out (Proc., 1896, 12, 42) that "the formation of a salt is presumably preceded by that of a combination of acid and alkaloid,' from which water is then eliminated. Just as the acid attracting

affected by the introduction, alkaloid '-attracting power of vary as radicles are introduced

power of the NH, radicle in aniline is say, of chlorine, so in like manner, the the carboxyl group may be assumed to in its neighbourhood in place of the hydrogen, more particularly in the case of benzenoid compounds."

Whatever the ultimate explanation of the behaviour of benzenoid acids and phenols, there can be little doubt that the phenomena of etherification must be viewed from the same standpoint as those of substitution generally, as there is complete parallelism between them. Armstrong has recently called attention (Proc., 1899, 15, 176; Chem. News, 1899, 80, 164) to the effects produced by introducing alkyl radicles in place of the hydroxylic and aminic hydrogen in phenols and amines, and to the remarkable manner in which the formation of substitution derivatives is inhibited. It is clear, in fact, that the influence of radicles in the nucleus on etherification, and, on the other hand, of etherification on the occurrence of substitution in the nucleus is reciprocal. This is further shown to be the case by the difference in the influence exercised by radicles according to their position-a single radicle in the meta-position relatively to the carboxyl of benzoic acid exercising less influence on the rate of etherification by alcohol and hydrogen chloride than does the same radicle in the para-position and much less than it does in the ortho-position. It is impossible to overlook the parallelism which such facts present with the phenomena of substitution expressed in the well-known " ortho-para" and "meta" laws.

CHEMICAL DEPARTMENT,

CITY AND GUILDS OF LONDON INSTITUTE

CENTRAL TECHNICAL COLLEGE.

V.-Contribution to our Knowledge of the Aconite Alkaloids. Part XV. On Japaconitine and the Alkaloids of Japanese Aconite.

By WYNDHAM R. DUNSTAN, F.R.S., and HAROLD M. READ, Assistant Chemist in the Scientific Department of the Imperial Institute. THE examination of the physiologically active alkaloid which exists in Japanese aconite roots has already formed the subject of several communications to this and other societies; but in view both of the conflicting statements as to its composition and relationship to aconitine and of the more recent work which has been carried out by one of us on aconitine and pseudaconitine (the crystalline, toxic alkaloids of

Aconitum Napellus and A. ferox respectively), it was thought desirable that the investigation should be extended to the alkaloids of Japanese aconite.

Japanese aconite roots seem to have come into commerce about twenty years ago; they are now imported regularly, and are regarded as more toxic than those of A. Napellus. An exhaustive report by Dr. A. Langgaard on "Japanese and Chinese Aconite Roots" was published in 1881 (Arch. Pharm., 18, 161), and from this it appears that, although the native practitioner employs many varieties of aconite, that most frequently used and exported is "Kuza-Uzu," which has been identified by various authorities as A. Chinense, A. Fischeri, and 1. Lycoctonum respectively.

A crystalline alkaloid was first obtained from Japanese aconite roots by Paul and Kingzett (Pharm. J., 1877, [iii], 8, 173). The alkaloid was soluble in ether, insoluble in water, and formed uncrystallisable salts. From the results of a single combustion for carbon and hydrogen, and one nitrogen determination, the formula C2H4309N was adopted. This, however, was not controlled by the analysis of the platinum salt. This alkaloid was said not to suffer hydrolysis into benzoic acid and a basic substance.

In 1879, Wright, Luff, and Menke extended their investigations of the alkaloids of other aconites to those of Japanese aconite. The general results of their work (Trans., 1879, 35, 387) may be briefly stated as follows:

1. The roots imported from Japan were considerably richer in active crystalline alkaloids, as well as in non-crystalline bases, than A. Napellus.

66 88

2. Only one crystalline alkaloid, named japaconitine, was present. This melted at 184-186°, and the formula C6H38021N2 was proposed, the base being regarded as the sesqui-apo-derivative of a parent substance having the formula C3H47019N. 121

3. Japaconitine formed readily crystallisable salts, especially with nitric, hydrochloric, and hydrobromic acids. The hydrobromide has the formula CH88O21N2,2HBr+5H2O.

4. The alkaloid could be entirely extracted from the roots by means of alcohol alone.

5. When hydrolysed, japaconitine furnished benzoic acid and a new base, japaconine, which was amorphous, and formed amorphous salts.

6. When either the parent base or the hydrolytic base is benzoylated, a derivative was formed containing four benzoyl groups for every C33 originally present.

For the hypothetical parent base, the formula

(C7H2O O)C26 H9O7N(OH);