alkali, 2-methyl-8-carboxy-3(-keto-3,4-dihydro1,4benzoxazine. Both of these substances are new compounds. Xeither 2 -methyl - 6-carboxy -3- keto-3,4-dihydro-l,4-benzoxazine nor 6-carboxy-3-keto-3,4-dihydro-l,4henzoxazine exerts either antipyretic or analgesic action in s-arious test animals.
in this series, as benzoxaaines without tile carboxyl group. or with other groups such as the methyl group, have h : n reported as bring of consiilcrablc medicinal valiii'
Summary :i-(cr-Bromopropioiiylarnill(~~-salicylic acid was synthesized and, from t iiis by trea.tmerit with ( 7 ) F. Hoffman, I A Rochr~ Cr, .I -(;., ilritidi p a t e n t 370,37> (Apr. 17, 1931); German p a t e n t , i d i , l l I (Apr. 18, l!W 1 , I'reiswrrk aiirl hIayer, E. 5 . patciil !,!I31 ,St17 :liar 20 1331:
. [CONTRIBUTION F R O M THE I)I3I'AR
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PITTSH W R G I I , PIC ?; N A . BROOKLYS,S.T. --
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r M i 2 S r O F ~'lfARMACOLOGl-, SCHOOI, OF M E D I C I N E , UNIVZRSITY O F
MARYIANI) ~
A New Method for the Purification of the Alcoholate of the Trimer of Hydroxypyruvic Aldehyde BY WILLIAME. EVANS,JR., C. JELLEFF CARRAND JOHN C. KRANTZ, JR. Hydroxypyruvic aldehyde is of interest owing to its relationship to the intermediate metabolites of glucose. This compound has beeii prepared by the oxidation of and by the photochemical decomposition of g1yoxal.j Evans and Waring' treated dihydroxyacetone with an excess of cupric acetate aiid removed the excess of copper by precipitation as sulfide. Friedemann2 employed the same method but did not separate the compound from solution. This process was objectionable 011 account of the formation of sulfur derivatives of hydroxyniethyl glyoxal which are toxic. Kiichlin aiid Boeseken3 decomposed the sulfur compounds with an excess of silver acetate a t 30" and subsequently removed the excess of silver as chloride. 11ynd4found that the use of silver acetate caused the formation of a highly polymerized product. He avoided the use of hydrogen sulfide by precipitatiiig thc cscess copper with bariurn iiydroxidr. 'i.hi: hariuni was then removed as sulfate. Norrish xiid Griffiths5 prepared small aninuiits of glycczrosonc. I-,? t h e photochemical decompositioii o f sly )sal and isolated it as the trimer c o x b i n d with one ntolecule of alcohol. Experimental Reparation of Hydroxypyruvic Aldehyde.-One
mol of dihydroxyacetone was dissolved in IO mols of water and treated a t room tenipcrature \\itti 2.2,; i1101sof lincly di(1) W . 1,. Evans a n d C 1: IVarinK, Trirs ] O L ' I { ~ . I L , 48, 2678 (1926). (2) T.E. Friedemann, J . Bqol. Chcrii.. 73, B:31 1.1027). (a) A. T. Kilchlin ant1 J. Bfie?eken. Re&. I r n e . chim., 47, 1011 (1928). (4) A. Hynd, Riochrnr. I . . 25, 1 ! (1031) (5) R . G. W. Norrish a n d I 0 A Griiiith,. ./ C/,eitz . v c , 28;1!1 (1938).
vided crystallized cupric acetate. The mixture was shakcti frequently in order t o keep the solution saturated with copper acetate. The reaction was allowed t o proceed until the calculated amount of cuprous oxide was precipitatvrl The usual period of timc iiecessary was five to seven dayi A t this timc a grayish-colored precipitate of cupric oxalate began t o appear. The escess of C u + + was then precipitated carefully by the addition of a calculated amount of a l!lC/o solution of oxalic acid. :Ifter filtering the solution was reduced to a small volume by distilling at 17 mm. a t 35". Successive portions of alcohol were added and tbe product was reduced to dryness a t 17 mm. The residue was then dissolved repeatedly in small amounts of absolute alcohol and precipitated by the addition of ether. The ether--alcohol solutions were worked up later, using the same procedure, to recover some of the product. Substances which wcrc insoluble iu water and in absolute alcohol were removed and the product was dried in vacuo a t i O o . T h e yield of thc product was 8 i % . After purification for biological use the yield was 64%. The product gave a negative test for Cui ' or oxalate. It was obtained as a pale yellow amorphous solid which melted between 1%; and 160' .I iyo aqueous solution exhibited a fiH of 3.12 at 2,;''. I t reduced I'ehling's solution and mcrcuric chlm 1-idc solution rapidly in the cold. No immediate reaction was obtained when Schiff's rcagent was added t o thc ircshly prepared solution but the characteristic color ap1)iwrd within scveral minutes. i l n a t . Calcd. Tor ( C ~ H I O ~ ) ~ , C ~ H C,~42.47; O H : H, 5.55; i i i i i l . \ \ t . , 310. Found: C,42.57; H, 5.42; mol. wt., 306. This is in agreement with the results obtained by Norrish and G r i f f i t h ~ . ~ On account of the ease of depolymerization, molecular wcight determinations had to he made with the greatest possible rapidity. The aqueous solution was depolymerized by long standing or by heating for ten minutes in a water-bath a t 60-70 '. Mol. w t . Calcd. for 3GH408 1C2HbOH: 7 i . R . Calcd. for 2C3H403 C3H4O3.C2H6OH: 103. Found 99.3. These mol. wts. confirm those of Norrish and GriffithsS Quinoxaline derivative: m. p. 25O--25lo; reported6 m. p.
+
i!i,-,'
+
SURFACEFILMSOF CHLOROGENIN AND DERIVATIVES
July, 1938
Pheqylglycerosazone: m.p. 132"; reported'*6m. p. 133". Hydroxymethylglyoxime: m. P. 134- 135". Reported' m. p. 168". Anal. Calcd. for CsHa03Nt: N, 23.7, Found: N, 23.4. An aqueous solution of the dioxime gave a red color with cobalt acetate in the presence of sodium acetate. On careful addition of dilute sodium hydroxide to this solution a green base was precipitated.
[CONTRIBUTION FROM
THE
1629
Summary 1, The alcoholate of the trimer of hydroxypyruvic aldehyde was prepared free from sulfur derivatives. 2' The quinoxaline phenylosazoneJ and dioxime were prepared. RECEIVED FEBRUARY 28, 1938 BALTIMORE, MD.
DEPARTMENT OF CHEMISTRY, STANFORD UNIVERSITY ]
Saponins and Sapogenins. VI. Surface Films of Chlorogenin and Derivatives By C. R. NOLLER
In the last paper of this series' the tentative formulas, I and 11, based on chemical evidence, CHs \1
I
CsHsO
'"ll cr]
CsHsO
compressible films indicating that the molecules are tilted or lying flat a t low pressure^.^ Hence it was expected that if formula I1 is a possibility for chlorogenin, the molecules in surface a m s would lie flat at low pressures and give a highly campressible film. The data plotted in curve I show that this is actually the case. The mole-
I CHs HO
\
/\ /\/
i
A / /-I
Ho/\'A I1
were proposed for chlorogenin. Formula I1 was favored because the ketodibasic acid obtained on oxidation did not appear to be either an aor a &keto acid as would be required by formula I. The second hydroxyl group was assigned to position 12, since the diketone forms a dioxime which would not be expected if the hydroxyl group is at position 11. 0 40 80 120 Recent work on the surface films of structurally Sq. A. per molecule. related compounds2 indicates that those moleFig. 1.-Pressure-area curves for surface films of: cules having one or two hydroxyl groups in the I, chlorogenin; 11, gitogenin; 111, chlorogenin diend-ring give incompressible films in which the acetate; IV, diketone from chlorogenin. molecules stand on end and occupy an area that is predicted by models of the compounds. Choles- c u l a occupy at low pressures an even larger area tanol-6 and A4~6-cholestenol-7 ($-cholesterol) hav- than +-cholesterol, the film being gaseous a t very ing hydroxyl groups in the second ring give highly low pressures. At higher pressures the curve appears as if it will coincide with that for gitogenin (1) iToller, THIS JOURNAL, 69, 1092 (1937) (2) Askew, Farmer and Kon, J Chem S O L ,1399 (1936)
(3) Adam, Askew and Daaielli, fiachem. J., PO, 1786 (1935)
