14 CHOLINE 



crystals from water; both forms of crystals are orange-red in color; very 

 insoluble in alcohol but moderately soluble in water. 



Bromoplaiinate (C5H14ON Br)2PtBr4: Melts at 240° (decomp.); large 

 dark- red prisms or octahedra; sparingly soluble in water. ^^ 



Picrate (CeHuON • CeHaOyNs) : Melts at 240°; readily soluble in water 

 and alcohol.''"' 



Complex with uranium [C5H]40N-U02(N03)2]2: Yellow, non-hygroscopic 

 crystals insoluble in ethanol and ether and sparingly soluble in water; 

 aqueous solution fluoresces in ultraviolet light.'*'' 



III. Industrial Preparation 



WENDELL H. GRIFFITH and JOSEPH F. NYC 



The reaction between trimethylamine and either ethylene chlorohydrin' • - 

 or ethylene oxide^ is used commonly in the manufacture of choline. 



(CH3)3N + CICH2CH0OH -^ (CH3)3N+CH2CH20H + CP 



(CH3)3N + CH2— CH., + HoO -^ (CH3)3N+CH2CH,OH + [OH? 



O 



In Hopf and Vierling's modification of the first reaction^ gaseous trimethyl- 

 amine is passed through ethylene chlorohydrin at 80°. In Korner's pro- 

 cedure* trimethylamine and ethylene oxide react in the presence of water 

 and carbon dioxide and the resulting choline is transformed to other salts 

 by treatment with various acids. 



Choline has been prepared more recently by a two-step synthesis.^ The 

 quarternary salt, 2-(ethoxymethoxy)ethyltrimethylammonium formate, is 

 formed by heating 2-(ethoxymethoxy)ethyldimethylamine with an excess 

 of methyl formate at 140 to 150° under a pressure of 250 p.s.i. The quar- 

 ternary salt is then refluxed in a mixture of ethyl alcohol and hydrochloric 

 acid, and the reaction mixture is taken to dryness at a reduced pressure. 

 The crude choline chloride remaining in the residue is purified by crystal- 

 lization from isobutyl alcohol. 



99 A. B. Weinhagen, Hoppe-Setjler's Z. physiol. Chem. 105, 249 (1919). 

 "o U. Suzuki, T. Shimamura, and S. Odake, Biochem. Z. 43, 89 (1912). 

 i«i C. Soye, Compt. rend. 228, 1228 (1949). 



1 R. R. Renshaw, /. Am. Chem. Soc. 32, 128 (1910). 



2 H. Hopff and K. Vierling, German Pat. 801,210 (December 28, 1950). 



3 F. Korner, French Pat. 736,107 (April 29, 1932). 



* W. F. Gresham, U. S. Pat. 2,457,226 (December 28, 1948). 



