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VOl. 80
O N THE STEREOCHEMISTRY OF THE PIMARIC with 0.08 N ammonium hydroxide. Kanamycin ACIDS B base is soluble in water, slightly soluble in the lower alcohols, insoluble in non-polar organic sol- Sir: vents, and decomposes over a wide range above In view of the stereochemical and possibly bio170°, +135 ( c 0.63, H20). I t gives positive genetic relationship of pimaric and isopimaric Molisch, Elson-Morgan and ninhydrin tests but acids (I) with other diterpenes,' elucidation of the gives negative reducing sugar tests and yields no configuration of especially their 13-substituents is furfural-like material after 40% sulfuric acid treat- most important. ment a t 100' for 100 min., in contrast to kanamycin. The infrared spectrum in KBr shows the following absorption maxima: 2.96, 3.41, 6.35. 6.48 (shoulder), 6.74, 6.85 (shoulder), 7.23, T 45, 7.86, 8.08, 8.28, 8.76, 9.55, 9.65, 10.4, and 11.13. Kanamycin B base was recrystallized repeatedly from 90% ethanol and dried to constant weight at 135' under vacuum. A n a l . C, 44.7, 44.5; H, CO,H kO,H 7.46, 7.55; N, 12.56, 12.55; neut. eq., 106; mol. IS wt., 1170 (Rast method with urea as solvent). Identical concd. sulfuric acid treatment of Kanamycin B was characterized as a polyacetyl for derivative, prepared from kanamycin B by acetic pimaric as well as isopimaric acids (I),--30' anhydride-pyridine acetylation. Acetylation of a fifteen minutes,-gave the previously reported hymixture of the antibiotics and countercurrent dis- droxylactone,?m.p. 180-15lo, I.R.(CHClp) 5.73p, tribution in a n-butanol-acetic acid-water system an oily mixture of 5 - and 6-membered lactones and (4:1:5)also yielded polyacetylkanainycin B, [a]? abietic acid (11), identified by the characteristic +107.8 (c 0.49, CH30H). A n a l . C, 50.68, 51.05; 241 mp ultraviolet absorption peak and the identity H , 6.52, 6.61; N, 7.55, 7.68; 0-acetyl, 25.4; total of the infrared spectrum and specific rotation of its acetyl, 46.3; mol. wt., 2010, 2220 (Signer). N- di-n-amylamine salt with that of an authentic Acetylkanamycin B was obtained by de-O-acetyla- specimen. These results constitute the first chemical tion with ,4mberlite IR-410 (OH-)2 of the poly- proof of the fact that isopimaric acid i s not u ruceacetyl derivative and by acetylation of kanamycin mate4 and represent the first chemical conversion of a B base in methanol with acetic anhydride. It de- pimaradiene to a n abietadiene, the jinal step in the composed gradually a t 220' to 250°, +150 generaliy accepted biogenesis of abietadienic diter(c 0.42, H20). A n a l . C, 48.23, 47.97; H, 6.81, Sulfuric acid treatment of dihydropimaric acid 6.78; N, 9.07, 9.14. Kanamycin B yields Schiff bases with aromatic aldehydes as does kanamycin.' a t room temperature for ten minutes led to a The N-salicylidene derivative was obtained by 1 . G : l mixture of 5- and 6-membered lactones,6 treatment of the base in water with an alcoholic respectively. Similarly, dihydroisopimaric acid solution of salicylaldehyde. A n a l . C, 58.15; H, yieldeda 1.0:lmixtureof a5-lactone)m.p. lO8-llOo,' [Q]D -15', and 6-lactone, m.p. 60-65°, [ a ] ~ 5.60. T h e production of non-identical sets cf Hydrolysis of N-acetylkanamycin B (1 HCI, -40'. 40 min. reflux) yielded 2-deoxystreptamine, iso- lactones f r o m the two dihydro acids under identical lated as the di-N-acetyl derivative and confirmed conditions of a reaction which perturbs all asymby infrared comparison with an authentic sample, metric centers except (2-4 and 13 proves that the resin and kanosamine, isolated as the pentaacetate and acids are at least 13-epimers. -4n infrared spectrophotometric product analysis confirmed by infrared comparison. Paper chromatograms of acid hydrolyzates of kanamycin B of an acid-catalyzed equilibration of dihydropisulfuric acid a t rocm show, in addition to deoxystreptamine and kanos- mark acid-concentrated the amine, an unidentified ninhydrin-positive reducing temperature for nineteen hours-indicated formation of 95 0.6% 6-lactone (111) and 5 0.6% spot but no spot for 6-deoxy-6-amino-D-glucose (6-glucosamine). The 6-glucosamine component 5-lactone (IV). Equilibration of pure 6-lactone of kanamycin yields a substance with an ultra- gave the same reaction mixture. However, similar violet spectrum similar to furfural when treated treatment of dihydroisopimaric acid led to a I 6-isolactone (111)and 3.6 =t0. with hot sulfuric acid. Kanamycin B does not ture of 96.4 O.SyO give this product, confirming the absence of G- 5-isolactone (117). Since the 6-lactones are the more glucosamine. Both kanamycin B and kanosamine stable products and since the change f r o m the 5 - to on treatment with SOY0 sulfuric acid yield a product the 6-lactones involves among other things a conformational inversion at C-13, the system with lowlev with the properties of an aminofurfural. 6-lactone content at e p i l i b r i u m must have its buifzieu
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*
H SCHMITZ
RESEARCH DEPARTMEYT BRISTOLLABORATORIES INC. SYRACUSE, XEWYORK
0. B. FARDIG F A. O'HERROS M A ROUSCHE
I R. HOOPER
RECEIVED *4PRIL 1, 1958 (3) M . 1. Cron, 0. B. Fardig, D. L. Johnson, H.Schrnitz, D. F. Whitehead, I. R . Hooper and R. U. Lemieun, Tma J O U R N A I . , 80, 2342 (1938).
(1) E. Wenkert, C h e m i s f v y and I n d u s f u y , 282 (1955). (2) E. E. Fleck and S. Palkin, THISJOURNAL, 62, 2014 (1940). ( 3 ) G. C . Harris and T. F. Sanderson, {bid., 70, 334 (1948). (4) C.f. 0 Jeger and A . Brossi, Helu. Chiin. A c f a . 3 3 , 722 (1950). (.i) L. Ruzicka, Exbcrieniza. 10, 357 (1953). (6) (a) T Hassetstram and B. L. Hampton, TITISJ O U R N A L , 61, 967 (1939); (bi Le-van-Thoi and J. Ourgaud, B u l l . sac. chiin , Friinru,
1388 (1955). (7) G. C. Harris and T. F. Sanderson, THISJ O U R N A I . , 70, 9081 (1948).
June 5, 1958
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13-substituent in an axial configuration. Thus pimaric acid is V a n d isopinzaric acid
Hydrolysis and ether extraction of the mixture are employed to obtain a mixed crystalline product which may be separated by fractional crystallization of the picrates. Under heterogeneous conditions about equal amounts of hexamethylbenzene, whose identity was confirmed by mixed m.p. and ultraviolet-infrared spectral comparisons with authentic substance, and 1,2,3,4-tetramethylnaphIV thalene, m.p. 107-108.5”, picrate m.p. 183.5-184.5’ [Anal. Calcd.: C, 91.25; H, 8.75; and C, 58.11; H , 4.63; N, 10.17, respectively. Found: 91.45; H, 8.59; and C, 58.13; H, 4.34; N, 10.551, hithertofore available by a five-step synthesis from prehnitene,5are formed. The condensation of 2-butyne on chromium may also be carried out homogeneously in tetrahydrofuran solution and in this case product control has The thus-derived C-13 stereochemistry of the been found to be possible. For example, if the pimaric acids implies that the biosynthesis of ring temperature of the solution is maintained a t 0’ for C takes place in a non-specific manner. Hence, the 3 days or a t room temperature for 3 hours, the sole stereochemistry of tetracarbocyclic diterpenoids, aromatic product is the naphthalene derivative ; phyllocladene, the aconite alkaloids, etc., cannot and if the solution is maintained a t room temperabe predicted with safety on biogenetic ground^.^ ture for -34 hours or heated to reflux for 2 hours, (8) The present chemical data corroborate the structural conclusions hexamethylbenzene is produced admixed with the from surface tension measurements of the pimaric acids [H. H. Brunn, naphthalene. However, the formation of the Acta Acad. Aboensis, Math. et Phys., 19, (3), 7 (1954)l. The authors tetramethylnaphthalene in this reaction may be are most grateful to Mr. L. J. Gough for first drawing their attention to this work. suppressed entirely by the use of triethylchromium (9) The authors express their gratitude to Drs. Lawrence and Lein tetrahydrofuran solution with -3-butyne, and in van-Thoi and Professor Jeger for gifts of the resin acids and to the this case the only aromatic product is hexamethylInstitute for Atomic Research, Ames, Iowa, for the use of a Baird benzene. infrared spectrophotometer. The product, hexamethylbenzene, arising from DEPARTMENT OF CHEMISTRY IOWA STATECOLLEGE ERNEST ~%’ENKERT the reaction between triphenyl- or triethylchroAMES, IOWA JAMES W. CHAMBERLINmium and 2-butyne clearly requires the intervention RECEIVED APRIL 5, 1958 of a n-complexed intermediate such as R3Cr(CH3C=CCH3)3, this being formed by replacement bf the ACETYLENIC T-COMPLEXES OF CHROMIUM I N coordinating tetrahydrofuran molecules in R3CrORGANIC SYNTHESIS’ (THF)s by 2-butyne, since this acetylene is unSir: affected either by chromic trichloride (or its tetraThe concept of the r-complexed intermediate hydrofuranate) or by phenylmagnesium bromide. originating from the interaction of sufficiently acti- The participation of the phenyl groups of triphenylvated n-electron systems, exemplified previously chromium in this condensation reaction leading to by aromatic Grignard compounds, with chromium the naphthalene by interaction of phenyl with two has led to the examination of other r-electron sys- molecules of 2-butyne in the r-complex and contems and of the prospects of isolating intermediates sequent ortho ring closure opens the way for the and final products arising from their reaction with synthesis of various condensed aromatic ring systhe transition metals. Evidence of the ability of tems by an appropriate choice of triarylchromium chromium to complex acetylenes and of the fusion and acetylene. These reactions will be reported of these complexes to aromatic structures has been later in detail. obtained. The description by Sternberg, Markby (5) M. C. Kloetzel, R. P. Dayton and H. L. Herzog, ibid., 71, 273 and Wender4 of the use of iron pentacarbonyl in (1950). Ultraviolet and infrared spectral comparisons confirmed the preparing duroquinone constitutes another example identity of the two samples. CENTRAL RESEARCH LABORATORIES of this phenomenon. We now wish to report a MOSSANTO CHEMICAL COMPANY H. H. ZEISS specific one-step synthesis of hexamethylbenzene DAYTOX 7. OHIO W. HERWIG and 1 2,3,4-tetramethylnaphthalenefrom 2-butyne RECEIVED MARCH15, 1958 via a n-complex synthesis on chromium as a prototype of a general synthesis of aromatic molecules PHOTOCHEMICAL REACTIONS OF KETONES I N from acetylenes. SOLUTION Triphenylchromium tri-tetrahydrofuranatel unSir: dergoes heterogeneous reaction smoothly with The mechanism of photolysis of ketones has been 2-butyne a t 20” within a period of several minutes. a subject of current and we wish tq (1) Paper V of “a-Complexes of the Transition Metals”; Paper IV, W. Herwig and H. H. Zeiss, THIS JOURNAL, 79, 6561 (1957). (2) H. H. Zeiss and W. Herwig, THIS JOURNAL,78, 5959 (1956); Ann., 608, 209 (1957). (3) H. H. Zeiss, “Handbook, X V I t h International Congress of Pure and Applied Chemistry,” July, 1957, Paris, p. 134. (4) H. W. Sternberg. R . Markby and I. Wender, THISJOURNAL, 80, 1009 (1958).
( 1 ) W. Davis, Jr., and W. A. Noyes, Jr., THIS J O U R N A L 69, , 2153 (1947). ( 2 ) A. J. C. Nicholson, Trans. Faraday Soc., 60, 1067 (1954). (3) T. W. Martin and J. N. Pitts, THISJ O U R N A1I ,7 , 5465 (1955). (4) P. P. Manning, ibid., 79, 5191 (1957). (5) J. R. McNesby and A. S . Gordon, ibid., 80, 261 (1958). ( 6 ) P. Ausloos, Can. J. Chem., 86, 400 (1958).
