AUGUST 19, 1921 ALSBERG : PHYSIOLOGICAL CHEMISTRY 337 



were anaesthetic. Indeed Filehne^" concluded that the benzoyl group 

 was responsible for the anaesthetic action. The action may be lacking 

 if there are interfering groups such as the carboxyl (COOH) group of 

 ecgonine. Moreover it was found that when, as in cocaine, the benzoyl 

 group was combined with a nitrogen-containing nucleus its action 

 became most apparent. Thereupon a large series of nitrogen-contain- 

 ing nuclei were benzoylated and it was found that so complex a nitrog- 

 enous nucleus as that of cocaine was not necessary. Many of these 

 benzoyl esters derived from quite simple nitrogen-containing nuclei 

 were found to have anaesthetic action. The first very simple sub- 

 stance of this type to find a practical use was orthoform, which is the 

 methyl ester of para-amino-meta-oxybenzoic acid: 



COOCHs 

 The objection to this compound is that it is too insoluble while its 

 salts are too irritant. It was therefore necessary to make soluble 

 derivatives. This was done by combining it with glycocoU (amino- 

 acetic acid) derivatives. Thus there was produced a substance which 

 has been used practically, nirvanin, the methyl ester of di-ethyl- 

 amine-acetyl-para-amino-ortho-oxy-benzoic acid : 



NH CO CH2 N(C2H6)2 



A 



.OH 



COOCH3 

 Further investigation showed that still greater simplification was 

 possible by the elimination of the hydroxyl group. This led to the 

 development of procaine, known by the trade name of novocaine, the 

 soluble hydrochloride of para-amino benzoic acid di-ethyl-amino- 

 ethyl ester or para-amino-benzoyl-di-ethyl-amino ethanol : 



NH2 



' COO-CH2-CH2N(C2H5)2HCl 



This is quite a simple substance as compared with cocaine and easily 

 made synthetically. Another simplification is the removal of the 



*° W. FiLEHNE. Die local anaesthesirende Wirkung von Benzoylderivaten. Berliner 

 klin. Wochenschr. 24: 107. Feb. 14, 1887. 



