PANTOTHENIC ACID 



oxidation with oxalic acid and hydrogen peroxide and neutralisation 

 with calcium carbonate. ^^ Yet another method of preparation com- 

 prised the oxidation of N-D-pantoyl-3'-hydroxypropylamine ^^ or 

 N-D-pantoyl-3' : 4'-dihydroxybutylamine ^^ or their derivatives first 

 with bariimi or potassium permanganate to give the aldehyde and 

 then with silver oxide to give pantothenic acid ; the N-D-pantoyl 

 hydroxyalkylamines were prepared by condensing pantolactone with 

 alkanolamines.^^ Resolution of DL-pantothenic acid was effected 

 through the quinine salt,^^ and pure calcium D-pantothenate was 

 prepared either by acidifying the sodium salt, neutralising with 

 calciimi carbonate and crystallising from alcohol ^^ or by adding 

 calcium chloride to a solution of the sodium salt in alcohol. ^^ 



National Oil Products Co. protected the preparation of pantothenic 

 acid by acylation of a salt of pantoic acid, conversion to the acid 

 chloride by treatment with thionyl chloride, reaction with a j8-alanine 

 alkyl ester, followed by hydrolysis of the resulting pantothenic ester.^* 

 Calcium pantothenate was prepared by reacting the calcium salt of 

 ^-alanine with pantolactone in anhydrous methanol or ethanol.^^ 

 Lederle Labs., Inc. prepared the calcium salt by the action of metallic 

 calcium on a mixture of jS-alanine and pantolactone ; ^^ by reacting 

 pantolactone in anhydrous alcohol with the calcium salt of /3- alanine, 

 prepared in situ from j8-alanine and calcium hydride, calcium amide, 

 calcium carbide, calcium hydroxide or cyanamide, but not metallic 

 calcium ; ^'^ or by the interaction of the calcium salt of ^-alanine and 

 pantoic a.cid amide in methanol. ^^ Parke, Davis & Co. protected the 

 preparation of sodium D-pantothenate, first, by heating jS-alanine 

 and sodium D-pantoate at 170 to 180° C. for fifteen minutes ^^ and, 

 secondly, by heating the sodium salt of jS-alanine with D-panto- 

 lactone in anhydrous ethanol or isopropanol.^^ 



Preparation of Pantolactone 



Since most of the methods of preparing pantothenic acid involve 

 the condensation of pantolactone with j3-alanine, considerable atten- 

 tion has been devoted to the preparation of these two substances. 



The method used by Stiller et al. (page 354) is the one in general 

 use, but minor modifications have been described in the patent litera- 

 ture. F. Hoffmann-La Roche & Co.,*^ for example, prepared panto- 

 lactone by the action of sodium cyanide on formylisobutyraldol 

 bisulphite compound and hydrolysis of the resulting cyanhydrin, 

 whilst Roche Products Ltd.^- prepared the optically active D-panto- 

 lactone from the racemic compound by treatment with chlorosul- 

 phonic acid and pyridine to give pantolactone hydrogen sulphuric 

 acid, fractional crystallisation of the strychnine salt of this acid and 



356 



