Oct. 5, 1952
4977
COMMUNICATIONS TO THE EDITOR
by complexing with the phosphate and by forming an ionic atmosphere about the phosphatea6v7 Condensed phosphates are believed not to form complexes with tetramethylammonium ions. We have hydrolyzed tetramethylammonium tripolyand pyrophosphates in solutions of ten per cent. tetramethylammonium bromide and in water.7 Sodium tripoly- and sodium pyrophosphates have also been hydrolyzed in sodium bromide solutions of the same ionic strength as the tetramethylammonium bromide solutions. The PH of these solutions was continuously controlled to h O . 1 PH unit a t pH 1, 4, 7, 10, or 13, whereas the temperatures were held a t 30, 60, 90 or 125'. In every case the concentration of the solution was adjusted to give one per cent. of orthophosphate ion on complete hydrolysis. The degradations from tripoly to pyro and from pyro to ortho were found to follow a first-order law. Although Watzel,s in agreement with other authors, finds a minimum rate for the hydrolysis of sodium tripolyphosphate at pH 10, our results show that the rate of hydrolysis of tetramethylammonium phosphate in 10% tetramethylammonium bromide solution continuously decreases with increase in pH from 1 to 13. The temperature dependence of the first-order rate constant, k, in hr,-I for the conversion from tripoly- to pyrophosphate can be given by the equation ; k = Ae--E/RTwhere A is the frequency factor and E is the activation energy. The variation of these quantities with PH is given in Figs. 1 and 2.
of IV yields 4-chloro-7-hydroxy-3-methylphthalide (VI), m.p. 101-103°, while pyrolysis of V yields 7-hydroxy-3-methylphthalide(VII) .6 Further evidence for the similarity of tho two terminal ring systems in aureornycin and in Terrarnycin is provided by the virtual identity of the difference curves obtained by the subtraction of the ultraviolet absorption of VI from that of IV, and VI1 from V. All eight oxygens in aureomycin have now been placed and, therefore, in addition to the substitution of a chlorine atom at Cle, aureomycin differs from Terramycin by the absence of a hydroxyl group at C12.' These deductions are supported by the recently described isolation of the acid (VIII) C1
CHa
//VO\pc00€3
v\!
\COO,
OCHa 0
VI11
from aureomycin by methylation, followed by permanganate oxidation.5 (6) F. Hochstein and R . Pasternack, THISJ O U R N A L 73 5008 (1931).
HIC OH
S(CHI)I
(7) Common to both Terramycin and aureomycin is the dructure A for which we propose the name tetracycline. 'Terramycin has, therefore, been assigned the generic name oxytetracycline.
RESEARCH LABORATORIES CHAS.PPIZERAND Co., INC. 6, N. Y. BROOKLYN
OH 0
OH 0 A C. R. STEPHENS L. H. CONOVER F. A. HOCHSTEIN P. P. REGNA F. J. PILGRIM K. J. BRUNINGS
*I
. lo201
I
I
CONVERSE LABORATORIES HARVARD UNIVERSITY R. B. WOODWARD CAMBRIDGE, MASSACHUSETTS RECEIVED AUGUST8. 1952
HYDROLYSIS OF CONDENSED PHOSPHATES
Sir: The ever-increasing importance of condensed phosphates and other polyelectrolytes to science and industry combined with the inadequacies and misconceptions of the published data on phosphate hydrolyses necessitated the initiation of a fundamental research program in this field. Some of the findings in the program are presented below. These results will be discussed more fully in a forthcoming paper. Condensed phosphates hydrolyze in aqueous solutions to yield less condensed phosphates and ultimately pure orthophosphate. The rate of hydrolysis is dependent upon the temperature, PH, concentration of and ionic environment. The ionic environment may affect the rate (1) J. Muns, 2. physik. Chem., 169A, 268 (1932). (2) S. J. Kiehl and E. Clanssen, THIS J O U R N A L , 67, 2284 (198.5) (3) R. Watzel, Die Chemie, €4,356 (1942) (4) R. N. Bell, I n d Eng. Chem., 89, 136 (1947).
(5) L.M.Postnikov, Ser. Fiz Mor. Esfrst. Nauk, S, 63 (1950).
101'1
I
1
I
.
,
7 10 13 Fig. 1.-Frequency factor for hydrolysis of 1% tetramethylammonium tripolyphosphate in 10% tetramethylammonium bromide solution as a function of pH.
1
q
10;. 1
4
7 10 13 PH. Fig. 2.-Activation energy for hydrolysis of 1 % tetramethylammonium tripolyphosphate in 10% tetramethylammonium bromide solution as a function of PH.
4
(6) J. Green, I n d . Eng. Chem., 42, 1542 (1950).
(7) J. R. Van Wazer, THIS JOURNAL, 72, 639 (1950).
.hi ionic atmosphere of tetramethylammonium hro,mde decreases the rate of hydrolysis in both x i t l i c and basic solutions. Thus, at R O O the tripolyto-pyro rate constant in hr.-I decreases from 0.46 to 0.37 at pH -1 and from 0.0172 to 0.0158 at p H 10 on adding ten per cent. of tetramethylammoniuni bromide to the tetramethylammonium tripolyphosphate solution. This is added proof that the hydrolyses of pyro- and tripolyphosphates are not catalyzed by hydroxyl ions. Aliswould be expected lroin complex formation, it was found that substitution of tetramethylammonium ion by sodium ion increases the rate of hydrolysis, and this increase is intensified by the presence of excess sodium. For example, a t 90' and pH 7 the tripoly-to-pyro constants in hr.-l are, for sodium ion, 0.192 and 0.152, and, for tetramethylammonium ion, 0.108 and 0.147, with the first number in each group corresponding to the presence of 0.6 IZT bromide of the respective cation and the second to a pure solution without swamping electrolyte.
a t 252 m p (.E 22,500) in 0.1 N sodium hydroxide and a t 247 mp ( E 1i,200) in 0.1 N hydrochloric acid. On refluxing 1 with hydriodic acid and red phosphorus a mole of ammonia and carbon dioxide is evolved, and a C5H602monobasic acid, I1 (pKa 4.5), m,p. 151-152' is isolated, anal. Calcd. for CjIlsO?: C, 61.22; H, 6.12. Found: C, 61.33; H , (i.3. This latter product was identified as 1 , 3 cyclopentanedione by oxidation t o succinic acid and by a positive iodoform reaction. The compound has a characteristic ultraviolet absorption spectrum with maxima a t 257 m p ( E 29,400) in 0.1 -V sodium hydroxide and 2-22 mp ( E 20,500) in 0.1 i27 hydrochloric acid. LVhen I is heated in -189; hydrobromic acid, a mole of ammonia and. carbon dioxide is evolved and a C5H,03 monobasic acid, 111 (pKa 3.0), m.p. 172.5-173' (dec.) is formed, unul. Calcd. for C5H403: C, 53.6; H, 3.57. Found: C, 53.36, H, 3.90. The ultraviolet absorption spectra are characterized by maxima at 310 m p ( E 13,450) in 0.1 S PHOSPHATE DIVISION RESEARCH LAH J . R T-AN b'AZER 1\IOVSANTO CIIFMICAL COHPA\V 13 J. GRIFFITH sodium hydroxide and a t 267 m p ( E 10,850)in 0.1 S r)qyli)Y, OITI~) J F ~ ~ C C l ~ I . l . C ) T 2 G I i hydrochloric acid. The compound was identified as 1,2,4-~yclopentanetrione by a positive iodoform RFCFIVEDJ U L Y3 1 , 103j2 reaction and by formation of an o-phenylenediamine derivative. Reduction of I11 with zinc and hydrochloric acid gives 4-hydroxy-l,%cyclopenDEGRADATION OF AUREOMYCIN. 111. 3,4-DIJ3Ytanedione, IV. This product and I11 can be conDROXY-2,5-DIOXOCYCLOPENTANEl-CARBOXAMIDE verted to 1,3-cyclopentanedione by treatment with Sir: hydriodic acid and phosphorus. The synthesis2 of The isolation and identification oi dixnethyl- I1 and I11 unequivocally proved their assigned structures. aminc. and 3-(4-chloro-7-h~~droxy-8-niethylphthaln'hen the pyridine salt of the triacetate of I is ide-:l -glutaric acid as degradation products oi aureoni).ciri have been outhied. Reported herein refluxed with acetic anhydride, a descarboxamido 11 is thc isolation and characterimtion of ;t CtiWS( triacetate, C6H30(OCOCH3)3, V, is formed. The co:llp~~und, 1. Thrsr drgradatioii products thus account ior the acetyl groups are removed by dilute acid hydrolysis carbon, cliloriiie :ind nitrogen of the original inolc- to yield a monobasic acid, C6H6O4, VI, m.p. 133154', m a l . Calcd. for c&O4: C, 46.2; H, 4.62. cult... \\.he11 aureomycin is treated with *\-sotliuiii Found C, 46.77; H, 4.84, positive iodoform reh!.tlrosidr, tlejtlimethylariiirioaureoiii~ciiiic acid, action. This acid is also obtained from barium hydroxide hydrolysates of I. On refluxing V or VI 111.1). 210-2112', ( 1 ~ ~ 1 1 . Calcd. ior C.:.H,,SCIOv: C, S-iel(l 3- ~ ~ - c l i l o r o - ~ - h ~ t l r o s ~ - 8 - m e t h y I p h t h a-l i d e - 3 , glutaric acid and ;i CIil-I:S05 inonobasic acid, 1, ,pKci 2 . & 11i.p. 1 9 -?()Os ~ (dcc.), ntznl. Calctl. ior CiH;SO:: C, 4!.\;: s c h , i r d tqi be published. c r:, !v,.lf.IA .I G ~ I , I I I ~ ~ I~Un . 1I I I \ \ ' I I I I , . I I I . . 'I'III.)(,I n\ 11 74 . A T ' I I ( 3 ) T h e stability of I is analogouq ti> t h e stability of C-acetyl d i m e (1,#-,2 dotie t o mlkarlinp r I ? : ~ v a ~Ae , J . H i r r h .I C'I!om. Yo.. ?I120 i l 9 T , I 1 , ,I'
I). 1.
