COMMUNICATIONS TO THE EDITOR
Jan. 20, 1953
499
THE TEMPERATURE OF THE CYANOGEN-OXYGEN FLAME Sir :
oxygen the flame consisted of two zones; the inner zone was a brilliant white comparable to that of a carbon arc. The outer zone had the blue color We have recently determined’ the temperature characteristic of the carbon monoxide flame in of the HrFz flame to be 4300 150’K. a t 1 atm. oxygen. In this work the outer zone was about 1” pressure, using a modified line-reversal technique, long and the inner zone l/4” to l / g “ in length. These with the sun in the heavens as the comparison ra- dimensions correspond to a total gas rate of about 200 cc. per minute. In these instances the flame diator. A much higher flame temperature is to be ex- burned right a t the tip of the torch. pected from thermodynamic considerations for The theoretical flame temperature as a function of the cyanogen-oxygen flame, according to the reac- inlet gas composition was calculated using the tion latest thermodynamic data7~8~9~10,11 (AGfor (CN)2dissociation = 114 kcal./mole) .lo These results ( C W ? k ) Oz(g) --+ 2CO(g) W g ) with the experimentally determined flame This reaction is exothermic to the extent of 126,680 together temperatures for various gas compositions are given cal. a t 298OK. Furthermore, the thermal stability of the CO and Nz molecules is even greater than in Table I. TABLE I that of the HF molecule. Experimental Theoretical Although the (CN)2-0~flame was studied many temp., temp., O K . Vol. %, Os, (CN): years ago,2,8its flame temperature bashever been 25.3,74.7 2580,2640 .. measured directly. This year Thomas, Gaydon 26.8,73.2 3090,3120 .. and Brewer4 measured the vibrational “tempera33.3,66.7 3270 3200 ture” of the flame molecules and obtained a “tem36.5,63.5 3333 .. perature” of 4800 200’K. a t the stoichiometric 50.0,50.0 4640 4810 composition. The calculated flame temperature 62.0,38.0 4453 .. reported by these authors was 4850 i 30°K., 66.7,33.3 4003,4043,4073,4143 3700 using the high value, Le., A# = 226,000 cal./mole The maximum experimental flame temperature or 9.76 ev., for the dissociation energy of Nz. They pointed out that by using the lower dissocia- was observed a t the stoichiometric point (30 vol. tion energy, Le., = 170,240 cal./mole or 7.38 % (CN),) in line with the above equation and eyuals ev., the calculated flame temperature was 4325’K., 4640O f 150’K. Thus at one atmosphere total thus fixing the dissociation energy of Nz at 9.76 pressure it is 340’K. higher than the hydrogenev. However, the vibrational “temperature” is fluorine flame and is therefore the highest directly not considered sufficiently representative of the measured flame temperature recorded to date. The theoretical flame temperature for the stoitrue thermodynamic temperature of the flame. chiometric composition is calculated to be 4810 This conclusion was reached in connection with our work on the HTFZ flame. The vibrational “tem- f 50’K. using the high value for the dissociation perature” of this flame was measured in our labora- energy of nitrogen. A temperature of 4375OK. tory by Drs. W. S. Benedict, S. Silverman and was obtained using the low value. The experiB. W. BullocP of the National Bureau of Stan- mental flame temperature is in good agreement dards and it was found t h a t the precision and with the higher theoretical flame temperature and reliability of direct flame measurements by the line- as such represents the first direct measurement of reversal method was greater than that of ,vibra- the cyanogen-oxygen flame temperature. (7) 0. P . Stevenson, J. Chcm. Phrs., 7, 171 (1939). tional “temperature” measurements. (8) H. M. Spencer and G . N. Flannagan, THISJOURNAL, 64, 2611 Our modified line-reversal method’ was again employed. The metered (CN)Z6 and 0 2 streams (1942). (9) J. W. Knowlton and E. J. Prosen, J . Res. 3 - d . Blrr. Stds., 46, were premixed in a 6-mm. glass tee filled with 20- No. 6, 489 (1951). (10) L. Brewer, L. R. Templeton and F. A. Jenkins, THIS JOURNAL, mesh quartz chips. A short length of quartz tubing acted as a torch tip. This tip was also 73, 1462 (1951). (11) National Bureau of Standards, Selected Values of Thermofilled with quartz chips and attached to the free dynamic Properties, API Project p44. end of the premixing tee by means of a piece of THE RESEARCH INSTITUTE OF J. B. CONWAY rubber tubing. The small oval-shaped opening in TEMPLEUNIVERSITY R. H. WILSON,J R . * the face of the quartz torch tip measured 0.134” PHILADELPHIA, PA. A. V. GROSSE X 0.031”. Small needle valves in the inlet gas lines RECEIVED OCTOBER 20, 1952 made it possible to vary the rate of either gas. The shape and structure of the flame varied with feed gas composition. Near the composition AMICETIN, A NEW STREPTOMYCES ANTIBIOTIC corresponding to one mole of cyanogen per mole of Sir: (1) R . H. Wilson, Jr., J. B. Conway. A. Engelbrecht and A. V. A Streptomyces sp., isolated from a soil sample Grosse, Tms JOURNAL, 78, 5514 (1951). collected near Kalamazoo, Michigan, was found t o ( 2 ) H. Dixon, J. Chem. SOC.(London), 49, 384 (1886). inhibit a number of bacteria when grown on an (3) A. Reis, Z. physik. Chem., 88, 513 (1914). agar streak plate. Mycobacterium tuberculosis var. (4) N. Thomas, A. G. Gaydon and L. Brewer, J . Chem. Phys., 20, 369 (1952). hominis (ATCC 607), Proteus vulgaris, Escherichia ( 5 ) See W. S. Benedict, B. W. Bullock, S. Silverman and A. V. coli, and Staphylococcvs aureus were markedly inGrosse, Phrs. K e u . , 87, 213-214 (1952). hibited when cross-streaked against this new iso(6) (CN)r was prepared by thermal decomposition of Ag(CN), coupled with stnndard purification. late. When the organism was grown in submerged
+
+
O K .
*
a
culture in a medium containing cerelose, yeast extract, soya flour and inorganic salts, the filtered fermentation liquor was found to inhibit Grani-negative and Gram-positive bacteria and particularly certain mycobacteria in both broth-dilution and agar plate assays. From these filtrates a crystalline antibiotic with pronounced antituberculous activity has been isolated and given the generic name miice tin. drnicetin was purified by extracting the clarified fermentation broth with n-butanol at pH i . 5 , removing the solvent by distillation, leaching the activity from the residue with water, lyophilizing the aqueous solution, fractionating the freeze-dried preparation by countercurrent distribution between water and methylene chloride, and finally crystallizing from water. Amicetin is a basic compound with $Xa's about 7. The crystals melted a t 16016Ei'. On warming to 50-70" in methanol or water suspension, they were converted to a granular highmelting crystal forfn of the free base with the properties: m.p. 243-244'; [LYl2'D +116.5' (c, 0.5 in 0.1 N hydrochloric acid); solubility in water a t 25', 1-2 mg. per ml.; only slightly soluble in common organic solvents. Amicetin exhibits characteristic ultraviolet absorption : in neutral aqueous = 465 a t 303 mp; solution a t the maximum in 0.1 X hydrochloric acid, EiZm = 433 a t 316 mp; = 470 at and in 0.1 N sodium hydroxide, 322 mp. Titration data and analyses indicate the formula CtgHuNaOe for the free base. (Anal. Calcd. for C2gH&JaOs:C, 56.11; H, 7.15; N, 13.54. Found: C, 55.98; H, 6.92; N, 13.18). The in vitro activity of crystalline amicetin free base against several bacteria is shown in Table I.
when tested in infected mice.' However, on a weight basis, amicetin does not appear to be as effective as Streptomycin sulfate when tested in this species. Preliminary studies indicate that the toxicity2 of amicetin varies considerably with the species. The acute intravenous LDs of amicetin as the citrate complex a t PH 6 in mice is approximately 90 tng. per kg.; the subcutaneous LD~o,(i00-iO0 mg. per kg. In rats the acute intravenous LDBO is . kg. and the subcutaneapproximately 200 n ~ g per ous LDm, about 600 mg. per kg. Amicetin is especially toxic to guinea pigs : by the subcutaneous route it is about forty times as toxic as streptomycin, but on the other hand only about one-tenth as toxic as penicillin to this same species. In contrast to streptomycin, amicetin does not appear to cause eighth-nerve damage when studied according to the procedure of Fowler and F e i ~ ~ d . ~ Detailed accounts of these studies are in preparation. (1) Determined by Charles Lewis, N. D. Connor and staff, Bacteriology Research Department, The Upjohn Company. (2) Determined by 0. F . Swoap, E. S. Feenstra, R . J. Cole, and P. M. Brockie, Pharmacology Department, The Upjohn Company. (3) E. P . Fowler and C. R . Feind, Am. Rev. Tub., 60, 39 (1949).
RESEARCH LABORATORIES C. DEBOER THEUPJOHNCOMPANY E. Lours CARON KALAMAZOO, MICHIGAN J. iv, I-TIXhfAX RECEIVEDDECEMBER 18. 1852
SYNTHESIS AND BIOCHEMISTRY OF 5- AND 7HYDROXYTRYPTOPHAN AND DERIVATIVES1 Sir :
The reported occurrense of serotonin (5-hydroxytryptophan) in serum12in intestinal mucosa (enteramin)3 and blood platelets (thrombocytin) as TABLE I well as in the parotid glands of Bufo marinup sugANTIBACTERIAL ACTIVITYOF CRYSTALLINE AMICETINAS gests, as mentioned previously,6 the possibility of a COMPARED WITH STREPTOMYCIN AXD THE CULTURE BROTH direct hydroxylation of the benzene ring in tryptoFROM WHICH AMICETIN WAS EXTRACTED phan prior to any reaction on the pyrrole part of Dilutions are expressed in microliters of broth or micro- the molecule. The alternative formation of serograms of solids per ml. required for complete inhibition of tonin from 5-hydroxyindole v i a 2,5-dihydroxyphenthe test organism. ylalanine' is unlikely, since the introduction of a 8Culture StreptoOrganism broth Amicetin mycin side chain into indole is a process unknown in Mycobacterium tuberculos1s animals. We now have synthesized 5- and 7-hy(H37Rv)' 0 5 1 0 droxytryptophan and their derivatives of actual and Mycobacterium tuberculosts potential physiological importance. (ATCC-607) 1 0 1 0 1 0 Catalytic debenzylation of 5benzyloxytryptoStaphylococcus aureus (FDAphan (m.p. B O o , dec.), obtained Via condensation 0 1 2 0 0 2 209) of 5-benzyloxygramine8 with diethylformaminomalBacillus subtzlis ( I l l . ) Klebsiella pneumonine (PCI-
004
602) Escherzchza colz (ATCC-26) Bodenheimer's cocco-bacillus
0 1
(PCI-3)
4 0
0 1
I0
>20 0 >20 0
0 2 1 0
1.0
>20 0
>40 0
I t is apparent that amicetin is active mainly against certain acid-fast and Gram-positive bacteria in contrast to the culture filtrates which have good Gram-negative activity as well. This is one of several indications that the Stre9tomyces sp. in question produces antibacterial activity in addition to that of amicetin. Crystalline amicetin has been found to be active in vivo against Mycokrferium tuberwlo is H37Rv
(1) Oxidation Mechanisms. VIII. Labile Amino Scid Metabolites. 11. C/. Expeyientio, 8 , 377 (1952). (2) hl. W. Rapport, A A . Green and I. H. Page, Scii,i~cr,108, 3251 (1948).
(3) V. Erspamer and H. hnsero, .\-afirre, 169, 800 11932); rf. A i,etreimitlelforsch., 2, 253 (1CJ52). (4) C . Reid and M. Rand, S a t w e . 169, 801 (1982). (3) S. Udenfriend, C. T. Clark and E . Titus, Experieulio, 8 , 3i!t (1952). (6) C.f. A. Ek, H . Kissman, J. B. Patrick and B. Witkop, i b i d . , 8 , 31; (19,52). (7) J. Harley-htason and R. I. 1'. Cromartie, Biochem. J . (Proc. Biochem. Soc.), 51, XXIV (1852); Chemistry a n d l i ~ d u s l r y 178 , (1852), J . Cham. Soc., 2525 (1952). (8) K. Ii. Hamlin and P. E. Fischer. THISJ O U R N A L , 73, 5007 (1951). We Ilsed the Robertson modification of the Nenitzescu-van der Lee synthesis for the preparation of 5-benzyloxyindole and increased the yield of the gramine to Y3% b y carrying out the Mannich condmsatior~ i n glarial acetic arid-dioxane under special prerautions.
