86 THE SIMPLER NATURAL BASES 



be the only one which is commercially suitable. The resolution of the 

 racemic adrenaline is effected according to Flacher [1908] by ex- 

 tracting the bitartrate with methyl alcohol ; d-adrenaline d-tartrate dis- 

 solves and 1-adrenaline d-tartrate remains behind. The latter yields 

 commercial synthetic suprarenin. 



An attempt to synthesise adrenaline by another method was originated by Barger and 

 Jowett [1905] and continued by Pauly and Neukam [1908], Barger [1908], Bottcher 

 [1909] and Mannich [1910], but has not yielded results of practical value (cf. German patents 

 Nos. 209609, 209610, and 212206). Starting from piperonal (I), Barger and Jowett pre- 

 pared the bromohydrin (II) which was converted into adrenalin methylene ether (III) 

 I II III 



O CH 2 



CHOH CHOH 



CH 2 Br CH 2 . NH . CH 3 . 



Adrenaline dimethyl ether was prepared from methyl vanillin by a similar method, but 

 neither ether is convertible into adrenaline. Mannich showed that on the addition of 

 methylamine to the bromohydrin, ethers of isoadrenaline^(OH) 3 C 6 H 3 . CH(NHCH 3 ) . CH 2 OH 

 are also formed. The indirect removal of the methylene group by conversion into an un- 

 stable cyclic carbonate e.g. OCO 2 : C 6 H 3 . CH(OH) . CH 2 C1, has also proved impossible. 1 



Another synthesis of adrenaline which is theoretically possible and has been referred to 

 in the patent literature, consists in methylating the primary base 3 : 4-dihydroxy-phenylethanol- 

 amine (OH) 2 . C 6 H 3 . CH(OH) . CH 2 . NH 2 . This base, which is about as active as adren- 

 aline itself and is known commercially as " arterenol," may be prepared by the reduction of 

 amino-acetocatechol> (D.R.P. 155632). 



(OH) 2 C 6 H 3 . CO . CH 2 . NH 2 + 2H = (OH) 2 C 6 H 3 . CH(OH) . CH 2 . NH 2 

 and also by the reduction of the cyanhydrin of protocatechuic aldehyde with sodium 

 amalgam (D.R.P. 193634). 



(OH) 2 C 6 H 3 . CH(OH) . CN + 4 H = (OH) 2 C 6 H 3 . CH(OH) . CH 2 . NH 2 . 

 Amino-acetocatechol is obtainable in several ways : 



1. From chloro-aceto-catechol and ammonia (the chief method) : 

 (OH) 2 C 6 H 3 . CO.CH 2 C1 + 2NH 3 = (OH) 2 C 6 H 3 . CO . CH 2 . NH 2 + NH 4 C1. 



2. By reduction of w-nitroacetocatechol : 



(OH) 2 C 6 H 3 . CO.CH 2 . NO 2 + 6H = (OH) 2 C 6 H 3 . CO.CH, . NH 2 + 2H 2 O. 



The w-nitroacetocatechol is obtained by hydrolysis of the corresponding methylene- or 

 dimethylether with aluminium chloride in benzene solution. These ethers, co-nitroaceto- 

 piperone and co-nitroacetoveratrone, may be prepared from piperonal and methylvanillin re- 

 spectively, by successive treatment with nitromethane, bromine, methylalcoholic potash and 

 acids (D.R.P. 195814). 



3. By hydrolysis with hydrochloric acid of the condensation product obtained from 

 veratrole and hippurylchloride by means of aluminium chloride (D.R.P. 185598 and 189483) 

 (CH 3 O) 2 C 6 H 4 + C1CO.CH 3 .NH.CO.C 6 H B =(CH 3 0) 2 C 6 H 3 .CO.CH 2 .NH.CO.C 6 H 5 + HC1. 



(CH 3 O)^C 6 H 3 . CO . CH 2 . NH . CO . C 6 H 5 + 3HC1 + H 2 O- (OH) 2 C 6 H 3 . CO . CH 2 . NH a . 

 A better yield is obtained by the hydrolysis of the similarly constituted phthalimido- 

 acetoveratrole (D.R.P. 209962 and 216640). 



1 Compare Pauly's repudiation [1909] of Bottcher's claim [1909] to have synthesised 

 adrenaline by this method and D.R.P. 209609, 209610, 212206. 



