| Caffeine | Theobromine | |
| C5HN2O3(CH3)3, | C5H2N2O3(CH3)2, |
so that in all, theobromine falls short of caffeine by only one radical. Strecker[54] was the first to show the relation between the two substances, when he succeeded in converting caffeine into theobromine by the action of methyl oxide on silver theobromine for 24 hours at 100° C. Caffeine and silver iodide are then formed and can be separated by treatment with alcohol, which dissolves the caffeine, leaving the silver iodide undissolved.
E. Fischer[55] was shown the relation of theobromine and caffeine to uric acid by artificial synthesis of both substances from derivatives of both. Fischer, starting with monomethyl pseudo-uric acid, converted it into 7-methyl uric acid by distilling it with hydrochloric acid, and afterwards, by treating the lead salt of the latter with methyl iodide and ether, produced 3-7-methyl-uric acid. That acid was converted into dimethyldioxychlor-purine by treatment with a mixture of phosphorus oxychloride and phosphoric penta-chloride, with subsequent reduction into 3-7 dimethyl-6-amino-2-oxy-purine, from which, by the action of nitrous acid with loss of the amine group, theobromine was finally obtained. The synthesis of theobromine is a brilliant exploit of Fischer’s, and it is quite possible that at no distant period, when a simple and cheap method of production has been arrived at, synthetical theobromine will appear commercially as a rival of the natural product. At present there is no prospect of this being immediately realised, and cacao shells from which theobromine is now prepared are as yet in no danger of displacement by the new substitute, but still serve as a useful by-product in the manufacture of cacao.
Theobromine and caffeine, like the alkaloids or plant bases, have a distinct physiological and even toxic action if taken in too large quantities.
From the experiments of Mitscherlich it appears that theobromine has a similar action to caffeine, but is somewhat less active owing to its being less soluble in the gastric juice. Mitscherlich’s experiments with frogs, pigeons and rabbits show that 0·05 grammes killed a frog in 40 hours, 0·05 grammes a pigeon in 24 hours, and 1 gramme a rabbit in less than 20 hours. Death resulted in all cases from cramping of the spinal cord, producing either convulsions or subsequent paralysis.
The results of these experiments do not detract from the nutritive value of cacao, since the human organism requires ten times as much theobromine as rabbits to exhibit the slightest toxic symptom; in cacao mass containing 1 % not mentioned in discussion; just a head’s up to PP for S&R] theobromine, that would involve the consumption of 5 lbs. averdupois of chocolate at once, a practical impossibility. Similar conditions prevail in connection with the use of tea, coffee, and especially tobacco, where symptoms of poisoning have been occasionally noticed (the nicotine peril of excessive smokers) but it would seem that cacao and chocolate are the most favourably placed of these stimulants as regards such toxic action. It appears from the experiments of Albanese[56] Bondzynski, Gottlieb[57] and Rost[58] that 3 percent of the theobromine administered passed out in the urine unaltered, whilst on the other hand 20-30 percent of that decomposed in the organism is found again as monomethyl-xanthine.
The larger proportion of the monomethyl xanthine is heteroxanthine (= 7 Methyl-X) and the inferior 3 Methyl-X. The excretion of theobromine appears to be closely connected with the quantity of urine voided, which is especially increased by the administration of theobromine. Since 1890, as a result of W. v. Schröder’s[59] observations in 1888, that property of theobromine has had an extended application in practical therapeutics; theobromine has been used as a diuretic in kidney diseases, and, unlike all similar medicinal agents, it exercises no influence on the heart, a circumstance which essentially increases its therapeutic value. It can be employed for medicinal purposes, either uncombined or in the form of salicylate, acetate and certain double compounds, as sodium or lithium and theobromine salicylate or acetate.
The double compounds known as diuretin, agurin and uropherin are freely soluble in water and are therefore more readily absorbed into the system than pure theobromine, which is only with difficulty soluble in water. Through the establishment of theobromine as a medicinal agent, for which we are indebted to Chr. Gram[60] and G. See,[61] cacao husks, hitherto a waste product in the manufacture of cacao, have become of value for the preparation of theobromine, in which many of the largest German chemical factories are now engaged.
Fluctuations as regards the percentage of theobromine in the beans are so extraordinary that they can only be ascribed to the lack of prescribed and definite modes of procedure in fermenting, which obviously necessitates differences in the resulting products.
Eminger found from 0·88-2·34 percent of theobromine in the examination of a rather considerable number of commercial kinds of cacao beans and in the husks 0·76 percent of the diureide: C. C. Keller[62] has also found it in the leaves and in the pericarp. Cacao contains 0·05 to 0·36 percent of caffeine.