Caffeine Theobromine ____________/\____________ ______________/\______________ / \ / \ C_{5}HN_{2}O_{3}(CH_{1})_{3}, C_{5}H_{2}N_{2}O_{3}(CH_{1})_{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.