III. INDUSTRIAL PREPARATION 399 



positive antihemorrhagic efficiency (somewhat after the mechanism pro- 

 posed by Quick and Collentine*^^). 3-Methyl-4-hydroxycoumarin also ap- 

 pears to have activity. ^^ This compound may be regarded as analogous to 

 phthiocol in which the 4-carbonyl has been replaced by an oxygen atom. 



Several reports have appeared of antihemorrhagic activity of phthalic 

 acid and its diesters.^^ However, Dam^" was unable to detect any activity 

 in potassium acid phthalate or diethylphthalate. Blumberg and Arnold^^ 

 carried out further investigations on this question but were unable to de- 

 tect any activity in diethyl-, dipropyl-, diisopropyl-, or dibutylphthalate, 

 even at high levels per chick. The diethyl ester also showed no antagonistic 

 action to methylnaphthoquinone. 



III. Industrial Preparation 



ROBERT S. HARRIS 



There is no important demand by the food industries for vitamins K 

 as concentrated from natural sources or as synthesized, because the amounts 

 present in the food supply and the amounts synthesized in the intestinal 

 tracts of most species, including man, are adequate for normal individuals. 



The clinical demand for vitamins K is now met by synthetic processes. 

 Concentrates prepared^ from natural sources are sometimes preferred be- 

 cause they contain vitamin Ki. Synthetic vitamin Ki is also available,^* ^ 

 but it is not wddely used because of high cost of production. Synthetic 2- 

 methyl-l,4-naphthoquinone^'^'' is now preferred in the clinic because it is 

 highly effective and least expensive to produce. 



67 A. J. Quick and G. E. Collentine, Am. J. Physiol. 164, 716 (1951); J. Lab. Clin. 

 Med.ZQ, 976 (1950). 



68 P. Meunier and C. Mentzer, Bull. soc. chim. biol. 25, 80 (1943). 



69 M. M. Shemiakin and L. A. Schukina, Nature 154, 513 (1944). 

 " H. Dam, Nature 152, 355 (1943). 



" H. Blumberg and A. Arnold, Proc. Soc. Exptl. Biol. Med. 57, 255 (1944). 



1 S. Ansbacher, E. Fernholz, and M. L. Moore, U. S. Pat. 2,233,279 (1941). 



2 H. J. Almquist and A. A. Klose, J. Am. Chem. Soc. 61, 2557 (1939). 



3 L. F. Fieser, J. Am. Chem. Soc. 61, 2559 (1939). 



* L. F. Fieser, W. P. Campbell, E. M. Fre.v, and M. D. Gates, Jr., J. Am. Chem. 



Soc. 61, 2559,3216 (1939). 

 6 S. B. Binkley, R. W. McKee, S. A. Thajer, and E. A. Doisy, /. Biol. Chem. 133, 



721 (1940). 

 6 R. T. Arnold and R. Larson, J. Org. Chem. 5, 250 (1940). 

 » P. P. T. Sah, W. Brull, and H. Holzen, Ber.73, 762 (1940). 



8 P. P. T. Sah, Rec. trav. chim. 59, 461 (1940). 



9 P. P. T. Sah and W. Briill, Ber. 73, 1430 (1940). 



loE. A. Poulsson, J. Soc. Chem. Ind. {London) 60, 123 (1941). 



