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Volume 38, 1905
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Art. IX.—Some New Compounds of a Similar Nature to Antifebrine.

[Read before the Wellington Philosophical Society, 5th July, 1905.]

Antifebrine, acetanilide, C6H5. NH. CO. CH3, is prepared by heating together acetic acid and aniline. The acetic acid may be replaced by any fatty acid, and the resulting compound is known as the anilide of the corresponding acid. Many of these compounds have already been obtained, but the melting-points of the known members of the series show such little regularity that it was determined to prepare the missing members in order to investigate the nature of the irregularities. Again, by treating the derivatives of aniline, such as toluidine, naphthylamine, &c., with the fatty acids, new series of compounds can be obtained, and these have hitherto been investigated only to a slight extent. No less than thirty-five new compounds of this nature have been prepared in a pure condition. Their medicinal properties have not been investigated, but it is quite possible that some of them might prove to be antipyretics as valuable as, if not more valuable than, antifebrine itself.

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In Table I are collected the melting-points of the anilides and paratoluidides. It is seen that the numbers do not form a regular series, but vary in a most erratic manner, the irregularities being greatest among the earlier members. In the case of the even members a regular increase in the melting-point is observable after the tenth member, and, further, the differences between the two sets of numbers gradually diminish.

[The section below cannot be correctly rendered as it contains complex formatting. See the image of the page for a more accurate rendering.]

Table I.
Number of Carbon-atoms in Corresponding Acid. Anilides. Difference. Paratoluidides.
° ° ° ° °
2 112 153
3 105 123
4 90 74*
5 61 72*
6 95 75*
7 71 80*
8 59*
9 57* 81*
10 61* 19 80*
11 64* 67*
12 68* 13 81*
14 84 9 93*
16 90 6 96*
18 94 4 98*

One of the causes of these abnormal results is probably the symmetry of the molecule, which has been shown in many cases to have a great influence on the melting-point. Hence, if in two series of compounds of similar nature symmetry in one case tended to reduce the melting-point, and in the other to cause an elevation, the possibility arises that these two factors might balance each other; consequently, on adding the melting-points together a regular series might result. This method of treatment has proved to be successful, and satisfactory results have been obtained, more especially in the case of the even members, for which the data are more complete.

A series of such a nature is that of the fatty amides, the melting-points of which tend to rise or fall as the corresponding numbers in the case of the anilides or paratoluidides diminish or increase. The values obtained by adding these series together is given in Table II.

[Footnote] * Determinations by the author.

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Table II,—Sum of Melting-Points.
Number of Carbon-atoms in Corresponding Amide and Anilide. Amide and Paratoluidide Acid.
° ° ° °
2 194 235
3 184 202
4 205 189
5 171 187
6 195 175
7 166 175
8 169
9 149 173
10 159 178
11 145 148
12 170 183
14 186 195
16 196 202
18 203 207

In both cases the numbers for the odd members fall continuously. In the even series there is a regular minimum, and in one instance a corresponding maximum at a distance of six carbon-atoms. The resemblance becomes clearer when the results are plotted graphically.

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In addition to these compounds the lower members of the naphthylamides have also been prepared. In each case the melting-points form an even less regular series than do the anilides and paratoluidides.

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Table III.
Number of Carbon-atoms in Corresponding Acid. α, Naphthylamide. Sum. β, Naphthylamide.
° °
2 159 291 132
3 116* 286 170*
4 120* 287 167*
5 111* 277. 166*
6 93* 264 171*
7 106* 248 142*
8
9 91* 200 109*
10 95* 194 99*
11 92* 191 105*
12 87* 185 98*

These series scarcely show any regularity even when the odd and even members are considered separately. But it is noticeable that when the melting-point of the α compound rises, that of the β derivative falls, and vice versa. Consequently, on adding the two series together it might be expected that regularities would appear. Such is indeed the case; the sum of the melting-points of the even as well as the odd members forms a gradually diminishing series of numbers.

The naphthylamides, even when recrystallized several times from alcohol, are of a pink or yellowish hue. But the most noticeable feature is that the odd members of the α compounds are much darker in colour than the even members, whilst in the case of the β derivatives exactly the reverse is found to be the case.

Experimental.

The anilides and toluidides described in the present paper were prepared by the following method: A mixture of from 1 to 3 grams of the fatty acid and the equivalent amount of aniline or paratoluidine was sealed in a tube and heated to 150°–180° for eight hours. In no case was any pressure observed in the tube after cooling. The product obtained in this manner was treated several times with dilute hydro-

[Footnote] * Determinations by the author.

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chloric acid to separate any uncombined base. After this the impure substance, which if it had first separated as an oil had in most cases now become solid, was washed with water and crystallized from dilute alcohol. Usually three crystallizations were sufficient to obtain a compound of constant melting-point. The yield was in general 50–80 per cent. The purified compound was then analysed by determining the percentage of nitrogen by the ordinary method of Dumas.

The following are the details of the experiments:—

Nonylanilide: C15H28ON; white crystals; M.P., 57°. On analysis, 0·2140 gram gave 11·7 c.c. N at 23°, and 768 mm. N = 6·3 per cent., (calc.) 6 per cent.

Decanilide: C16H25ON; white crystals; M.P., 61°. On analysis, 0·1098 gram gave 5·7 c.c. N at 22°, and 758 mm. N = 5·9 per cent., (calc.) 5·7 per cent.

Undecylanilide: C17H27ON; white crystals; M.P., 64°. On analysis, 0·1968 gram gave 9·6 c.c N at 23°, and 768 mm. N = 5·6 per cent., (calc.) 5·3 per cent.

Lauranilide: C18H29ON; light-yellowish crystals resembling lauric acid; M.P., 68°. On analysis, 0·3376 gram gave 14·6 c.c. N at 20°, and 770 mm. N =5·1 per cent., (calc.) 5·0 per cent.

Butyroparatoluidide: C11H15ON; white crystals; M.P., 74°. On analysis, 0·1502 gram gave 10·3 c.c. N at 23°, and 764 mm. N = 8·0 per cent., (calc.) 7·8 per cent.

Valeroparatoluidide: C12H17ON; white crystals; M.P., 72°. On analysis, 0·1474 gram gave 9·6 c.c. N at 19°, and 750 mm. N = 7·5 per cent., (calc.) 7·3 per cent.

Hexoparatoluidide: C18H19ON; white crystals; M.P., 75°. On analysis, 0·2194 gram gave 13·4 c.c. N at 22°, and 754 mm. N = 7·0 per cent., (calc.) 6·8 per cent.

Heptoparatoluidide: C14H21ON; white crystals; M.P., 80 per cent. On analysis, 0·2560 gram gave 14·2 c.c. N at 22°, and 756 mm. N = 6·3 per cent., (calc.) 6·4 per cent.

Octoparatoluidide: C15H23ON. Separated as a brown oil, which crystallized only after several weeks. After four recrystallizations a small quantity of the compound, melting constantly at 59°, was obtained. The amount was insufficient for analysis. The small yield in this case is probably due to the fact that it is extremely difficult to prepare octoic acid in a pure state.

Nonylparatoluidide: C16H25ON; white waxy crystals; M.P., 81°. On analysis, 0 1962 gram gave 9·8 c.c. N at 21°, and 754 mm. N = 5·7 per cent., (calc.) 5·7 per cent.

Decoparatoluidide: C17H27; whitish crystals; M.P.,

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80°. On analysis, 0·1646 gram gave 8 0 c.c. N at 23°, and 756 mm. N = 5·5 per cent., (calc.) 5·3 per cent.

Undecylparatoluidide: C18H29ON; waxy white crystals; M.P., 67°. On analysis, 0·1924 gram gave 8·5 c.c. N at 23°, and 758 mm. N = 5·0 per cent, (calc.) 5·0 per cent.

Lauroparatoluidide: C19H31ON; yellowish crystals; M.P., 81°. On analysis, 0·2780 gram gave 12·1 c.c. N at 22°, and 756 mm. N = 5·0 per cent., (calc.) 4·8 per cent.

Myristoparatoluidide: C21H35ON; waxy white crystals; M.P., 93°. On analysis, 0·2042 gram gave 7·6 c.c. N at 21°, and 760 mm. N = 4·35 per cent., (calc.) 4·4 per cent.

Palmitoparatoluidide: C23H89ON; yellowish crystals; M.P., 96°. On analysis, 0·2618 gram gave 9·2 c.c. N at 21°, and 764 mm. N = 4·1 per cent., (calc.) 4·05 per cent.

Stearoparatoluidide : C25H48ON; after six crystallizations from absolute alcohol the compound melted at 90°. On analysis, 0·2710 gram gave 9·0 c.c. N at 22°, and 764 mm. N =3·9 per cent., (calc.) 3·75 per cent.