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



By boiling p-toluidine with haliotropin and pyro-racemic acid, £-piperonyl-£-methyl- 

 quinoline-4-carboxylic acid is produced 1 ). 



Further heliotropin, when boiled in alcoholic solution with ^-aminophenol and pyro- 

 racemic acid, produces £-piperonyl-£-hydroxyquinoline-4-carboxylic acid which is then 

 purified over its sodium salt 2 ). 



By condensing heliotropin with o-anisidine and pyroracemic acid £-piperonyl- 

 #-methoxyquinoline-4-carboxylic acid is produced which can than be purified by means 

 of repeated precipitation from its alkaline solution 3 ). All these acids are remedies for 

 gout and rheumatism in the joints, the £-phenylquinoline-4-carboxylic acid (phenyl- 

 cinchoninic acid) has, however, the disadvantage of possessing a rather bitter taste. 

 Piperonyl cinchoninic acid, on the contrary, is far more palatable, although its therapeutic 

 effects are just as satisfactory. Salicylic aldehyde is employed for the producing of 

 £,#'-diquinolyl-£,£'-dihydroxyphenyl-4,4'-dicarboxylic acid and in point of fact by con- 

 densating it with pyroracemic acid and benzidine 4 ). 



By boiling p-aminoacetaldehyde, alcohol, pyroracemic acid and anisic aldehyde, one 

 obtains the acetylated £-^-methoxyphenyl-£-aminoquinoline-4-carboxylic acid which 

 produces the free acid on saponification ; as a derivate of quinoline it is of importance 

 from a therapeutic standpoint and is said to exercise a similar effect to atophan 5 ). 



Heliotropin which is obtained from safrole 6 ) is also remarkable as a raw material 

 for the production of woquinoline compounds amongst which hydrastinine. plays an 

 important part. 



The first original synthesis of hydrastinine was performed by P. Fritsch 7 ). He coupled 

 piperonal (heliotropin) with aminoacetale, forming piperonal aminoacetale, and obtained 

 from the latter by closing the ring 6, 7-methylenedihydroxyisoquinoline which he trans- 

 formed into hydrohydrastinine by means of methylation and subsequent reduction. 

 Fritsch's synthesis, however, gave no good yields in practice and has accordingly been 

 abandoned for technical purposes. 



All later syntheses whose elaboration has been mainly the merit of H. Decker and 

 A. Pictet start from homopiperonylamine which is produced according to various 

 methods that, however, one and all have to employ heliotropin. — 



If one allows formaldehyde to react with homopiperonylamine, so-called Schiff base 

 is formed, namely methylenehomopiperonylamine which can be readjusted to produce 

 the isomeric norhydrohydrastinine. As, however, the aldehyde is a strong methylating 

 agent the reaction between formaldehyde and homopiperonylamine can be so conducted 

 as to form hydrohydrastinine directly. One can also arrive at the same result by 

 letting methylhomopiperonylamine act on formaldehyde 8 ). The product of the reaction 

 of formaldehyde on homopiperonylamine is formylhomopiperonylamine which is trans- 

 formed by internal coupling into £,7-methylendihydroxy-3,4-dihydro-z'soquinoline (nor- 

 hydrastinine) and the latter by means of methylation turns into the hydrastinine-salt. 

 Inversely, one can first methylate the homopiperonylamine, then obtain the formyl 

 compound from the methylhomopiperonylamine, and finally couple the latter directly 

 to hydrastinine 9 ). 



!) D. B. P. 281603; Chem. Zentralbl. 1915, I. 232. — *) D. B. P. 246078; Chem. ZentralU. 1912, II. 1677. - 

 ») D.B. P. 281603; Chem. Zentralbl. 1915, I. 232. — 4 ) D. B. P. 246078; Chem. Zentralbl. 1912, II. 1677. - 

 B ) D. R. P. 294159; Chem. Zentralbl. 1916, II. 707. — e ) Cohn states that safrole is the main component of 

 caraway oil; he probably meant carvone, as caraway oil does not contain any safrole. — 7 ) D. B. P. 86561 ; 

 Chem. Zentralbl. 1896, II. 224. — 8 ) D. B. P. 257138; Chem. Zentralbl. 1913, I. 1154. — H. Decker and P. Becker, 

 Liebigs Annalen 395 (1913), 342, 351. — . 9 ) D. B. P. 234850; Chem. Zentralbl. 1911, II. 112; D. R. P. 245095; 

 Chem. Zentralbl. 1912, I. 1267; Liebigs Annalen 395 (1913), 382. 



