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The dimethylamino group is cleaved readily from terrainycin by the action of zinc and glacial acetic acid a t room temperature. The remaining carbon skeleton is accounted for by the isolation in good yield of a pale yellow crystalline compound ( m p . 175-180', dec. ). A d . Calcd. for CzoHnlNOs: C, 59.55; 11, 5.25; S,3.47. Found: C, 39.23; BIOLOGYDIVISIOX JOSEPH X. KHYM 13, 5.-11; N, 3.38, 3.59. This compound does tiol lorm a hydrochloride and is a stronger acid than OAKRIDGENATIONAL LABORATORY r,EOhl4RI) P. zII.1, OAK RIDGE,TENNESSEE terramycin. RECEIVED Mmcrr 17, 1951 Further details of the degradation of terramycin will be published as the work progresses.
clude other hexoses, the pentoses, and the disaccharides, i t has promise of wide application to many of the separations and analytical problems involved in investigations of sugars and other compounds which are capable of forming charged borate complexes. Further studies are in progress and will be published later.
Sir: This is a preliminary report on the most significant degradative reactions carried out in our laboratory on the new broad spectrum antibiotic, terramycin.1,2 Terramycin, CzzHz~-z~NzOg, is readily degraded by the action of aqueous alkali. On boiling a 20% aqueous sodium hydroxide solution of terramycin, one mole each of ammonia and dimethylamine are evolved within 24 hours. When the hydrolysis is carried out in the presence of zinc, a number of crystalline products can be isolated. The major product, isolated in 50% yield as a white crystalline compound, has been named terracinoic acid (imp. 232-234') dec.). Anal. Calcd. for Cl3HI206: C, 59.09; H, 4.58. Found: C, 59.17, 59.09; 13, 4.40, 4.84. Terracinoic acid is a tribasic acid with PKa values 2.6, 4.7 and 9.1. Among the products isolated in relatively low yield from this reaction mixture is a white crystalline phenolic lactone (m.p. 110-112°). Anal. Calcd. for CgH8O3.Hz0: C, 59.33; H, 5.54; HzO, 9.89. Found: C, 59.32; H, 5.79; HZO (K.F.), 9.30. Acetic acid and carbon dioxide are also produced in this alkaline degradation. Salicylic, m-hydroxybenzoic and succinic acids have been isolated from a potassium hydroxide fusion of terramycin carried out a t 200". The carbon skeleton of terramycin is cleaved less readily in acidic media. Terramycin is slowly rearranged by two equivalents of 1 N hydrochloric acid a t GO" to yield a yellow crystalline hydrochloride (m.p. 198-202', dec.). Anat. Calcd. for CzzHzaNzOe~HC1: C, 53.17; H, 5.07; N, 5.64; C1, 7.14. Found: C, 53.37; 13, Ti.33; N, 5.57; C1, 7.23. This rearrangement product is optically active but has no biological potency. The free base is a stronger acid than terramycin. More vigorous treatment of terramycin in acid solution results first in removal of dimethylamine and carbon dioxide, and finally in the loss of the second nitrogen function. Among the products of vigorous acid treatment are: (1) a crystalline derivative (m.p. 210-213', with prior darkening) Anal. Calcd. for ClgH17NOs:C, 58.91; H, 4.39; N, 3.62. Found: C, 59.11; H I 4.60; K, 3.45; and (2) an air-sensitive nitrogen-free compound (decomposes over a range 215-245' without melting). Anal. Calcd. for C 1 6 H 1 2 0 6 : C, 62.50; H, 4.20. Found: C, 62.12; H, 4.38. (1) A. C Finlay, et a i , Sczcncc, 111, 85 (1950) (2) P. P. Regna, I A. Solomons, A E. Timreck, K K.J. Brunings and W. A Lazier, 1 ~ 1 lourwar, 8 111 preqa.
R. PASTERN.4CK PETERP. RECNA BROOKI.YN 6 , NEW I'ORK RICHARD L. WAGNER A. BAVLEY I?. -4 IIOCHSTEIN PHILIPN. GORDON I(.J. BRUNINGS RECEIVED APRIL 6, 1951
ItESEARCH ~ ~ A B O R A T O R I E S CIiAS. PFIZER AND CO , IVC
DEGRADATION OF TERRAMYCIN
Murai,
BROMINATION OF HECOGENIN ACETATE
Sir : Current interest in the synthesis of cortisone from 12-ketosapogenins prompts us to report some preliminary results of work with hecogenin. I n considering the introduction of an oxygen atom a t C-11 by hydrolysis of 11,23-dibromohecogenin acetate (I) we were first concerned with the stability of the halogen in 23-bromohecogenin acetate' toward hot alkaline hydrolysis; i t was found to be resistant toward such treatment since 23-bromohecogenin was the product. The acetate is unchanged in the presence of boiling pyridine. Further bromination resulted, however, in I , whose structure was assigned on the basis that removal of hydrogen bromide in pyridine gave an a,P-unsaturated ketone, designated as 11, whereas mild alkaline hydrolysis removed only one of the bromine atoms with simultaneous hydrolysis of the ester to give 111. I n view of the stability of the 23-bromoketospirane side chain under the conditions used these reactions place the reactive bromine a t C-11. This assignment is supported by similar studies in the bile acid series from which, also, a method is indicated for preparing the 11-keto derivatives by hydrolysis of the halides and rearrangement of the resulting 11-hydroxy-l2-ketones in hot alcoholic. alkali2 Hydrolysis of 23-bromohecogenin acetate yielded 23-bromohecogenin, m.p. 210' (dec.)3, [ C Y ] ~ ~ D -3.0" (dioxane). Calcd. for C2,H4104Br: C, 63.64; H, 8.11; Br, 15.68. Found: C, 63.10; H, 8.05; Br, 15.64. Bromination of the acetate in glacial acetic acid a t room temperature with a slight excess of bromine gave 11,23-dibromohecogenin acetate (I), m.p. 173' (dec.), [cY]"D -21.4' (ethanol). Calcd. for C29H4206Br2:C, 55.24; H, 6.72; Br, 25.34. Found: C, 55.52; H, 6.79; Br, 25.37. Treatment of this product with hot pyridine yielded 9, (1l)-dehydro-23-bromohecoge( 1 ) R. E. M a r k e r , K. B. Wagner, P. R.Ulshafer, E. L. Wittbecker, D. P. J. Goldsmith a ~ i dC. 11. Ruof. THISJOURNAL, 69, 2167 (1947). (2) Cf. T F. (;allxgher, J . Bid. Chem., 162, 539 (19.46): T. F. Gallagher and E.Rorgstrom, ihid., 164,701 (1946). (3) All melting p o i n t s were o h s c r v d at fifty niagnitications on the KoEer hot stage and itre rortcctrd.
May, 19.51
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111 ( X = Br) IV ( X = H )
nin acetate (11), m.p. 228-230' de^.),^ [ a I z 6 ~duration of the experiment are shown below; no -24.6' (chloroform), Xg5%max. 240 ~ I J(log E solvents were used. The dehydrogenation of the 4.06), 311 mp (log e 2.08). Calcd. for C29Hd106Br: benzyl alcohol is accompanied by the reduction of C, 63.38; H, 7.52; Br, 14.54. Found: C, 63.79; the free radical corresponding to the substances H, 7.92; Br, 14.38. On cold, alkaline hydrolysis mentioned in Table I. Thus, from (I) the lactone 11,23-dibromohecogenin acetate formed ll-hy- of o-hydroxydiphenylacetic acid (111) was obtained, tetraphenylhydrazine yielded diphenylamine a n d droxy-23-bromohecogenin (111), m.p. 234.0-234.2' ~ D (dioxane). Calcd. for CZT- diphenyl disulfide yielded thiophenol. (dec.), [ L ~ ] ~-23.7' Hd106Br: C, 61.70; H, 7.87; Br, 15.21. Found: Ph 1 C, 61.77; H, 7.65; Br, 14.83. Reduction of the latter with zinc in acetic acid yielded ll-hydroxyhecogenin (IV), m.p. 216-2185', [ a ] " ~-37.1' (dioxane). Calcd. for C27H4205: C, 72.61; H, 9.48. Found: C, 72.36; H, 9.68. Treatment I I1 I11 with acetic anhydride in pyridine gave a diacetate, ~ (dioxane). Calcd. m.p. 230-231', [ a ] 2 e-70.7' TABLEI for CalH~07: C, 70.16; H, 8.74. Found: C, Temp. OC Hours 69.95; H, 8.63. The structures of I11 and IV follow tentatively 2,2'-Diket0-3,3-diphenyl-3,3'-dicoumnmnyl' (1) 110 2 from the identity of the hydrolysis conditions with 2,2'-Diphenyl-thioindigo white2 (11) 130 2 those which yielded lla- and ll~-hydroxy-l2-keto140 2 cholanic acids from the corresponding l l p - and Tetraphenylsuccinodinitrile*s6 110 1 lla-bromo derivatives.2 Treatment of IV with Tetraphenylhydrazine' 100 5 hot alcoholic alkali, as with pyridine or chroma- Diphenyl disulfide6 tographic alumina, gave rise to a mixture of isoMe' found also that phenyliodo dichloride (C&,meric substances having the composition of hy- ICh) converts benzyl alcohol into benzaldehyde droxyhecogenin and giving variously fractions when the two substances are heated a t 110' for 20 ~ to -37'. melting in the range 210-220°, [ a ]-27 minutes, whereas xanthhydrol was readily converted This indicates a rearrangement with the possible into xanthone. It is believed that these two reacformation of some of the expected ll-keto-12-h~- tions also proceed via a free radical mechanism, tlroxy isomer. I n view of the pyridine-acetic an- involving chlorine atoms. The yields of benzaldehydride conditions for formation of the diacetate as hyde (estimated through the 2,4-dinitrophenylwell as the failure of the latter to form an oxime, hydrazone) were good, in some cases exceeding the structure of this compound is not assigned. 70%. Further investigation of the keto1 rearrangement is (1) LLiwenbein and Simonis, Bet.., 67, 2040 (1924). in progress. (2) Kalb and Bneyer, ibid., 46, 3870 (1913). (3) Lowenbein, i b i d . , 68, 606 (1925); Wiltig, ibid., 66, 7 G O (!%E). We wish to thank the Research Corporation for (4) Wieland, A n n o k n , 881, 200 (1911). making this investigation possible. ( 5 ) Schonberg and Mustafa, J . Chcm. Soc., 889 (1949); Scllijn-
r
DEPARTMENT OF CHEMISTRY GEORGE P. MUELLER berg, Rupp and Gumlich, Be7., 66, 1932 (1933). E. STOBAUCH (6) This experiment was carried out with M. F. S. El-Hawary. ROBERT UNIVERSITY OF TENNESSEE KNOXVIILE,TENNESSEE ROBERT S. WINNIFORD DEPARTMENT OF CHEMISTRY 31, 1951 RECEIVED JANUARY FACULTY OF SCIENCE ALEXANDER SCHONBBRG FOUADI UNIVERSITY AHMEDMUSTAPA ABBASSIA-CAIRO, EGYPT DEHYDROGENATION REACTIONS BY THE ACTION RECEIVED DECEMBER 1, 1950 OF FREE RADICALS
Sir : Very little seems to be known about the strong dehydrogenating power of long-lived free radicals. We have found that the compounds listed in Table I, which all dissociate into free radicals of long life, a t least a t high temperatures (see footnotes l d ) , dehydrogenate benzyl alcohol to benzaldehyde. Experimental details concerning temperature and
ABSOLUTE MOLAL ENTROPIES OF TRANSFER OF IONS
Sir: I n a recent paper' Goodrich, Goyan and others have calculated absolute molal entropies of trans(1) J I, Goodrich, F M Goyan, E E Morsr K v U l l ~I l y I U U R N A ~ ,7a, 4-111 (1950)
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