202 G. DANGSCHAT, H. O. L. FISCHER VOL. 4 (1950) 



A sample twice redistilled was used for analysis: 



5.068 mg gave 11.195 rng COj and 2.860 mg HjO; 

 3.169 mg gave 0.151 ml Nj (26° and 741 mm). 

 C12H15O4N (237.1): Calc. C60.7 H 6.4 N 5.9 

 Found C 60.8 H 6.3 N 5.4 



Hydrolysis of acetyl-methylene-shikimic acid nitrile to methylene-shikimic acid 



3.3 g distilled acetyl-methylene-shikimic acid nitrile were boiled for two and a half hours with 

 45 ml N sodium hydroxide (about 3 molecules). A condenser was attached to take off the water 

 vapours and the ammonia. Water was added to the distillation flask during boiling so that the volume 

 was not reduced below one-half the original. The condensate was caught in an ice-cooled receiver 

 and at the end of the time the ammonia could be determined almost quantitatively. No formaldehyde 

 was found in the distillate even after acid hydrolysis. The reaction liquid, which was coloured dark 

 brown, was cooled and the alkali was neutralized by addition of 41 ml N sulphuric acid and 4 ml 

 N hydrochloric acid. The weak acetic acid solution was reduced to dryness in the best vacuum ob- 

 tainable by a water pump, during which time the bath temperature was not allowed to rise above 35°. 

 The residue was extracted thoroughly several times with ethyl acetate, and the united filtered extrac- 

 tions were evaporated under reduced pressure. If crystals are at hand for inoculation, the yellow 

 syrup remaining will begin to crystallize on inoculating. 33-38% of the theoretical yield of crystal- 

 lized methylene-shikimic acid was obtained from the concentrated ethyl acetate solution, but these 

 crystals still had a yellow colour. Using animal charcoal, a recrystallization from ethyl acetate was 

 made for further purification. 



The substance, well crystallized in rhombic plates, had a m.p. of 138° and showed no depression 

 of the melting point on addition of an equal quantity of a preparation made from shikimic acid. The 

 preparation twice recrystallized gave in aqueous solution the following rotation: 



[a]Jf° = _88.7°i7 (I dm tube, c = 2.17, a^ = —1.93°). 



Further quantities of the acid could be obtained from the motherliquor of the isolated methylene- 

 shikimic acid in the following manner: The methylene-shikimic acid methyl ester was formed by 

 esterification with diazomethane and was distilled under a high vacuum at a bath temperature of 

 170-190°. It was then kept for two to three days at 37° together with pyridine and toluene sulphonyl 

 chloride. The toluene sulphonyl-methylene-shikimic acid ester (m.p. and m.p. of the mixture 1 18-1 19°) 

 crystallized out readily on gradual addition of water and trituration. This isolated quantity corres- 

 ponds to a further 15-20% of the theoretical yield of methylene-shikimic acid, so that together 

 about 52% of the acid obtained from the nitrile can be definitely identified as a derivative of the 

 shikimic acid. The methylene-shikimic acid is easily isolated and identified by preparing its toluene 

 sulphonyl-methyl ester, which readily crystallizes. This process is to be recommended, if no inocula- 

 tion crystals of the free methylene-shikimic acid are at hand or if difficulties appear during the isola- 

 tion of the free acid. After washing with 50% alcohol the ester is at once obtained in the pure state. 

 For analysis and optical determinations it has to be recrystallized once more from alcohol: 



5071 mg substance gave 10.090 mg COj and 2.350 mg HgO 

 7921 mg substance gave 5170 mg BaSO^ 

 CisHigO^S (354.2): Calc. C 54.2 H 5.1 S 9.1 

 Found C 54.2 H 5.2 S 9.0 

 [a] ff° = —42.5° (in chloroform)i8 (i dm tube, c = 3.25, a^ = —1.38°). 



Hydrolysis of the unsaturated acetyl-isopropylidene nitrile 



The hydrolysis of the unsaturated isopropylidene nitrile can be carried out under the same mild 

 conditions as the corresponding methylene compound. In this reaction the ammonia can also be 

 determined nearly quantitatively after about two hours boiling with dilute alkali. Furthermore, it 

 was found that 25% of the theoretically possible amount of acetone was split off by the alkali. The 

 acetone could be determined in the distillate by titration with alkaline hypoiodite solution and 

 identified as the ^-nitro- or dinitrophenylhydrazone. The further processing parallels the procedure 

 used for the methylene nitrile. From the acetonated compound, however, it was not possible to isolate 

 the free acetonated acid, nor to crystallize a derivative of the acetonated unsaturated ester, which 

 had been obtained by esterification with diazomethane and subsequent distillation in a high vacuum. 

 If, however, the unsaturated ester, of which 27% of the theoretical yield was obtained by distillation, 

 is hydrolysed by acetic acid, about 4.5% of the theoretical amount (based on the amount of nitrile 

 used) is obtained in crystallized form^® as shikimic acid methyl ester. After two recrystallizations 

 from ethyl acetate and ligroin, the m.p. was 112-114° ^.nd there was no depression of the melting 

 point when the substance was mixed with equal amounts of a compound prepared from shikimic 

 acid for comparison. 



References p. 203/204. 



