142 Report of Schimmel § Co. April/October 1917. 



With the object of producing i-benzylhydrastinine, homopiperonylamine is heated 

 with phenylacetic acid, the resultant phenylacylhomopiperonylamine boiled with toluene 

 and phosphorus pentoxide, and the i-benzylnorhydrastinine thus obtained finally treated 

 with methyl iodide. 



5-Alkylhydrastinines are prepared by first combining <7-alkyl-iV-(aralkyl)homopiper- 

 onylamines with formic acid and then treating them with an acid coupling medium 1 ). 

 In order to produce 3-methylhydrastinine, one starts thereby from methylenedihydroxy- 

 phenyl-i^-methylformyhsopropylamine; ^-methyl-i^-ethylnorhydrastinine is prepared from 

 S-methyl-Mormyhsopropylamine by heating it with phosphorus pentoxyde in toluene 

 solution and treating the resulting 3-methylnorhydrastinine with ethyl iodide. 



Cotarnine is another important alkaloid; a number of its salts (styptol, stypticin) 

 have been introduced into medical circles as hemastatics, but it is not so useful as 

 hydrastinine from which it differs by having one methoxyl-group more. Accordingly 

 the syntheses of hydrastinin can be adapted with the necessary variation also for the 

 manufacture of kotarnin. 



Two general methods are known for the synthesis of cotarnine, one having been 

 discovered by H. Decker 2 ) and the other by A. H. Salway 3 ). 



In both cases the raw material is myristicine which is transformed via myristicin- 

 aldehyde into methoxyhomopiperonylamine. Decker obtains cotarnine from the above- 

 mentioned base according to a method analogous to that of the preparation of hydrastinine, 

 whereas Salway proceeds in a different fashion. 



Decker lets formylhomomyristicylamine react with phosphorus oxychloride in a 

 solution of toluene and works up the resultant norcotarnine as usual. 



Salway treats phenylacylhomomyristicylamine with phosphorus pentoxide; thereby 

 a mixture of two isomeric bases is formed which are separated from each other by 

 means of fractionated crystallization of their hydrochlorides. One of them is 1-benzyl- 

 norcotarnine, the other i-benzylneocotarnine. The former is transformed into the 

 methylchloride which produces ^-benzylhydrocotarnine by the agency of reducing 

 substances, whereupon oxidation leads to cotarnine, the benzyl gfoup being split off. 

 Hydrocotarnines which are substituted in the position 1 can be prepared like the 

 corresponding hydrohydrastinines by the action of organic magnesium compounds on 

 cotarnine. For practical purposes, the chloride of the base and an excess of Grignard's 

 solution is employed in order to obtain a good yield. 



The synthesis of berberine starts from homopiperonylamine which one couples 

 with homoveratric acid chloride and thus obtains homoveratroylhomopiperonylamine. 

 This amide is then condensed in the usual manner .into a dihydro*'soquinoline derivative, 

 the latter reduced by the aid of tin and hydrochloric acid to a tetrahydrotsoquinoline 

 derivative which finally reacts with methylal producing tetrahydroberberine. The raw 

 material for the manufacture of veratric acid is either eugenol or vanillin. Berberine 

 is prepared from tetrahydroberberine as usual by oxidation. 



Finally, only the synthesis of laudanosin remains to be discussed for which purpose 

 veratric aldehyde (methyl vanillin) is used, which, when coupled with acetic anhydride 

 and sodium acetate leads to dimethoxycinnamic acid, the latter producing dimethoxy- 

 hydrocinnamic acid by the aid of reducing agents. This acid is then transformed with 

 the help of its amide into homoveratrylamine 4 ). 



!) D.B.P. 279194; Chem. Zentralbl. 1914, II. 1174. — *) D. R. P. 245095; Chem. Zentralbl. 1912, I. 

 1267. — Lieligs Annalen 395 (1913), 328. — 8 ) Journ. chem. Soc. 97 (1910), 1208. Comp. also F. L. Pyman, 

 ibidem 95 (1909), 1738. — 4 ) A. Pictet and M. Finkelstein, Compt. rend. 148 (1908), 925. — Berl. Berichte 42 

 (1909), 1979. 



