Progress in Alkaloidal Chemistry During the Year

1904.*

*

By H. M. Gordin.

B-i-Cinchonine. K. Kaas finds that the substance obtained by melting the sulphate of 3-i-cinchonine (which is a tertiary base and contains an OH group) is a secondary base and contains a CO group. As the transformation is the same as that which takes place when tertiary cinchonine containing an OH group is changed to secondary cinchonicine containing a CO group, the substance obtained by melting -i-cinchonine sulphate should be named chonicine, not 3-i-pseudocinchonicine as had been proposed.

-i-cin

That -i-cinchoninicine is really a secondary base was shown by the formation of the hydriodide of N-methyl-i-cinchonicine when the base is treated with methyl iodide. The presence of a CHз group linked to the nitrogen atom in the methylated base was shown by Herzig and Meyer's method and that the CH3 group was not linked to oxygen was shown by the negative results obtained by Zeisel's method.

Another anology between B-i-cinchonicine and cinchonicine was found in the fact that when the iodomethylate of B-i-cinchonine is heated with potassium hydroxide, hydriodic acid is eliminated and the resulting compound is identical with the one obtained by methylating B-i-cinchonicine. In exactly the same way the iodomethylate of cinchonine when heated with potassium hydroxide is converted into methylcinchonicine. (See page 123.)

* Continued from page 125.

An attempt to prove the presence of a CO group in B-i-cinchonicine by means of phosphorus pentachloride did not give the desired results only one chlorine atom entered into the compound instead of two as should be expected from a ketone. As there was evolution of hydrochloric acid in this reaction it is probable that at first the oxygen atom of the CO group is replaced by two chlorine atoms but that the dichlorcompound soon looses hydrochloric acid and is converted into the monochlorderivative.

Monatshefte f. Chem. 1904, 1145.

Cocaine. C. Reichard gives the following new reactions for the detection and identification of cocaine.

1. If to a rather concentrated cold solution of a cocaine salt a solution of sodium nitroprusside be added the solution becomes turbid and, with the aid of a magnifying glass, small crystals of a reddish color can be noticed in the liquid. Morphine salts do not give this reaction.

2. If to a quite concentrated solution of cocaine hydrochloride a strong solution of uranium nitrate be added a yellow crystalline precipitate is formed which is most probably a double salt of cocaine and uranium.

3. If some titanic acid be dissolved in warm concentrated sulphuric acid and to the cooled solution be added some cocaine hydrochloride there is no reaction whatever in the cold even on prolonged standing. But if the mixture be warmed in a porcelain dish till stripes and oily drops appear on the sides of the vessel a beautiful blue or violet color is developed which is very stable. On adding water to the liquid a blue precipitate settles at the bottom of the vessel. The reaction is undoubtedly due to the reduction of titanic acid by the methyl alcohol formed in the saponification of the alkaloid by the sulphuric acid.

4. If to a mixture of potassium methylsulphate and sulphuric acid a little cocaine hydrochloride be added and the mixture warmed a strong peppermint odor is developed which is permanent for a long time.

5. On warming cocaine hydrochloride with a mixture of urea and sulphuric acid the mixture assumes a blue color which becomes deeper as the temperature rises. If in this reaction ethylene diamine be substituted for urea there is first an evolution of hydrochloric acid but on applying heat the blue color appears.

Chem. Ztg., 1904, p. 299.

C. E. Carlson finds that in testing cocaine hydrochloride for the presence of reducing substances (cinnamyl cocaine) by means of potassium permanganate and sulphuric acid it is best to leave out the sulphuric acid altogether. The sulphuric acid seems to retard the velocity of the reaction changing in some way the reducing substance. It was also found that if the sulphuric acid be added after the potassium permanganate the retardation is less than when the order is reversed. Pharm. Centralhalle, 1904, p. 69.

Coffearine. L. Graf corroborates the statement of P. Paladino (Ber. Dtsch. Chem. Ges. 1894, 406. R.) about the existence in coffee of the alkaloid coffearine.

That this alkaloid is not formed by the action of the calcium oxide, which Paladino used in his method of extraction, upon coffeine was shown by the fact that no coffearine could be obtained by the author from coffeine by treating it with calcium oxide. On the other hand coffearine was obtained from aqueous extracts of coffee even without the use of calcium oxide.

The formula of coffearine, C14H16N2O4, established by Paladino was found to be correct.

Zeitschr. öffentl. Chem., 1904, p. 280. Conhydrine. K. Löffler has investigated the constitution of conhydrine, pseudoconhydrine and of some of the coniceines.

As both conhydrine and pseudoconhydrine give the same a-pipecolinic acid upon oxidation the OH group in both these bases must be situated in the side chain (Willstätter, Ber. Dtsch. Chem. Ges. 34, 3166).

Of the three theoretically possible oxypiperidines containing the OH group in the side chain one was prepared synthetically by Ladenburg and found to have the constitution of an a-pipecolylmethylalkine

As there are two assymetric carbon atoms in this compound it

ought to exist in four optically active modifications and two racemic modifications. Conhydrine and pseudoconhydrine can be assumed to be two of the four optically active forms; the synthetic a-pipecolylmethylalkine is one of the racemic modifications and is chemically identical with conhydrine.

The chemical identity of conhydrine with a-pipecolylmethylalkine was shown by the following experiments:

1. On heating the synthetic a-pipecolylmethylalkine with fuming hydrochloric acid to 220° water is eliminated and two isomeric bases are formed which are very similar to a-coniceine and B-coniceine respectively previously obtained from conhydrine by the same method. The salts obtained from the two bases were also found to be almost identical with those obtained from a-coniceine and B-coniceine respectively. The only difference between a-coniceine and B-coniceine on one hand and the bases obtained from a-pipecolylmethylalkine on the other is that the former are optically active while the latter are inactive. The latter must therefore be assumed to be the racemic forms of a-coniceine and B-coniceine respectively.

The reaction according to which conhydrine or its isomer ɑ-pipecolylmethylalkine are converted into coniceines is as follows:

2. On heating a-pipecolylmethylalkine with hydriodic acid and amorphous phosphorus two isomeric compounds are obtained which contain an atom of iodine instead of the OH group. Both these iodine containing bases behave exactly like the iodine derivatives obtained from conhydrine by the same method.

3. On treating the iodine compounds obtained from the a-pipecolylmethylalkine with sodium hydrate, hydriodic acid is eliminated and the bases thus obtained are identical with e-coniceine previously obtained by Lellmann from conhydrine by the same method, i. e., replacing the OH group by iodine and then splitting off hydriodic acid by means of alkali. The reaction takes place according to the following equation:

The only difference between -coniceine and the bases obtained from the iodine derivative of a-pipecolylmethylalkine is that e-coniceine is optically active while the bases from a-pipecolylmethylalkine are inactive. We can again assume that these bases are the two racemic forms of e-coniceine.

Attempts to split up synthetic a-pipecolylmethylalkine into its active components and thus obtain bases in every respect identical. with conhydrine and pseudoconhydrine were not successful. No crystalline compounds could be isolated.

Ber. Dtsch. Chem. Ges., 1904, p. 1879.

Cotarnine. J. J. Dobbie, A. Lauder and C. K. Tinkler show that the changes in the spectrum of cotarnine produced by equivalent amounts of different alkaline hydroxides and by ammonia can be utilized for establishing the relative strengths of these substances. As had been shown in a previous paper (See this Review, 1904, Progress in Alkaloidal Chemistry during 1903) cotarnine exists in two forms: a carbinol form and an ammonium hydroxide form

which have different spectra both in the free condition and as salts. The addition of alkali to a solution of the yellow ammonium form changes the cotarnine to the colorless carbinol form. On using equivalent amounts of different alkaline hydroxides and ammonia and observing the changes produced in the spectra it was found that