of glacial acetic acid was added to t h e cold, stirred ~ulutioii over a period of 1 hr. The dark orange solution was allo\vetl t o stand a t room temperature for 16 hr. The solutioti \ \ : I \ was then heated until evolution of HBr ceased (1.5 hr. 1, :iiitl the acetic acid solvent was removed by steam distillation. The dark, tarry residue was extracted with ether. Thc ethereal extract was filtered and shaken with 6 .\' NaOH. s.37. The bright yellow precipitate was filtered anddecrystallized Infrared spectra (Nujol) of both the alkaloid from water; yield, 60 g., darkening at 240 , completely isolated by chromatography and the alkaloid melted a t 265". Apparently some impurity in this material poisoned the isolated by fractional crystallization were identical palladium catalyst used in catalytic debromination, so tht. with the spectrum of yohimbine. material mas dissolved in water and the solution acidiiietl with 2 N HzSO,. The acidified solution was extracted \\-it11 RESEARCH DEPARTMENT ether, and the extract was shaken with 6 N S a O H . Thc CIBAPHARMACEUTICAL PRODUCTS, IXC. butter-yellow precipitate was filtered, washed with colt1 SUMMIT,NEW JERSEY brine and recrystallized from 95% ethanol. This rn:rtcrial was found to darken a t ca. 240' and melt a t 250-260°. Although a mixture of materials was expected, :dl a t Formation Constants of Metal Complexes of tempts t o separate the yellow material failed. Paper cliroinatograms, developed with FeC13, indicated that only O I I V Tropolone and its Derivatives. 11. Some active compound was present. Alkyltropolones1,2 p-Methyltropo1one.-Five grams of the above iuatcri:il, 1 g. of 10% palladium-charcoal and 200 ml. of 95% ctli:tnol BY B U R L E. BRYANT3 4 N D 1Tr. CON.4RD F E R N E L I U S were shaken under HZuntil uptake ceased (1.5 h r . ) . The RECEIVEDDECEMBER 16, 1953 ethanol was stripped under vacuum and the residue \ v a s extracted with ligroin. The extract yielded 1.6 g . of mateThe investigation of metal complexes of tropo- rial, melting 60-63". Repeatef recrystallization yielded lone4 has been extended to include the dissociation 1.3 g. of material, m.p. 69-70 . A sample of p-rnethylconstants of methyl- and isopropyltropolones and tropolone furnished b y Professor T. A-ozoe mas found to 73-74". A mixture of the two samples melted 69the formation constants of some complexes of these meJt 70 . Anal. Calcd. C, 70.6; H, 5.88. Found: C, 70.0; substances with divalent metal ions. H, 5.92. 2-Methylcycloheptanone .--From 129 g. of cyclohcxanoiie, Experimental 40 g. (27.4%) of 2-methylcycloheptanone, b.p. 36" ( 2 n u n . ) , 1.4534, was prepared in a manner similar to that preThis investigation mould not have been possible without viously mentioned5 by the generation in situ of diazoethaiie the kindness of others in supplying samples of most of the from nitrosoethylurethan. The low yield, compared to that substituted tropolones. To Professor T. A-ozoe of Tohoku reported for a different method6 can be explained by the fact University, Sendai, Japan, Tve are indebted for the a-isopropyltropolone ( m . p . 33-34'), 0-isopropyltropolone (m.p. that the nitrosoethylurethan was used without purification. 3-Methylcycloheptane-1 ,Z-dione .-In a manner analogous S o )and , for samples of 01- and 6-methyltropolone; t o Professor A. B . Anderson of the University of California for t o the SeO? oxidation described above, 127 g. of 2-inethylcycloheptanone yielded 30 g. ( 17.3y0) of ~-niethT-lcycloEiepy-isopropyltropolone (m.p. 78-79'); and t o Professor H . Erdtmann of The Royal Institute of Technology, Stockholm, tane-l,Z-dione, b.p. 65' ( 3 m m . ) , i t 2 0 ~1.4787. a-Methylbromotropo1one.-Thirty grams of the :il>ovc Sweden, for P-isopropyl-y-(3-methylbut-2-enyl)-tropolone. diketone in 30 ml. of glacial acetic acid \vas cooled to I)', Ring Expansion of 4-Methylcyclohexanone.--Five hunand 78 g . of bromine in 30 ml. of glacial acetic acid \v:i\ dred grams of 4-methylcyclohexanone was allowed to react added t o the cold, stirred solution dropwise over :t period of with diazomethane by the same procedure used by Kohler, 4 hr. The temperature was maintained at 0' throughout Tishler, Potter and Thomsonj to prepare cycloheptanone addition of bromine. The dark solution \vas allowed to from cyclohexanone. Fractionation of the reaction mixture yielded 375 g. (67%) of 4-methylcycloheptanone, n z o ~ stand for 16 hr. a t room temperature. The major portion of the acetic acid was then removed under reduced pressure 1.4590, distilling at 78" (16 mm.), and 110 g. of unreacted and the residue was steam distilled. The distillate dcpo\4-methylcyclohexaIioiic . ited cream-colored needles which were separated, :iiitl t hc Oxidation of 4-Methylcycloheptanone.-A solution of distillate was extracted with toluenc. The tolucnc \v;is 378 g. ( 3 moles) of 4-mcthylcycloheptanone in 700 nil. of evaporated aiid the residue \vas recrystallized from 0.5% absolute ethanol was brought t o reflux in a 5-liter flask ethanol; fine, cream-colored needles, m . p . 1 2 l 0 , yicltl X g . equipped with a reflux condenser, a n efficient stirrer, and L: dropping funnel. Over a period of 1.25 hr., a solution of (17%). a-Methyltropo1one.-The bromo coinpoutid \vas t l i i 333 g. (3 moles) SeOzin 500 ml. of absolute ethanol and 1600 solved in ether and shaken with 6 .V NaOH to yicltl the nil. of 95% ethanol \ \ u s added r'ie the dropping funnel. sodium salt of a-methylbromotropolone, brilliant yellolv The solution was refluxed a n additional 6 hr., and allowed powder, darkening a t ca. 2 6 5 O , completely black a t 29%5" to stand a t room temperature for 18 hr. The precipitated but failing t o melt below 300". Ten grams of the salt was selenium was filtered, and the filtrate boiled with Norit. dissolved in 270 ml. of 95% ethanol and 1 g . of lOy0 PdAbout 1 liter of ethanol mas distilled a t atmospheric pressure, and the solution again filtered. Distillation was con- charcoal was added. The solution mas shaken under H? tinued under vacuum. There was obtained 145 g. (55%) until hydrogen absorption ceased. The catalyst was filtered and the alcohol was removed from the red solution a t room of a viscous, yellow material, boiling 79-103' ( 3 mm.). Bromination of Diketone.-A solution of 140 g. (1.64 temperature under reduced pressure. The residual red oil was extracted with ligroin. The extract deposited light moles) of t t e diketones in 200 ml. of glacial acetic acid was cooled to 0 , and 520 g. (3.25 moles) of bromine in 200 ml. cream-colored plates upon chilling in acetone-Dry Ice. The crystals were filtered and the same ligroin used for cx(1) Taken in part from a dissertation presented by Burl E. Bryant traction until chilling failed to induce further crpstnlliznin partial fulfillment of t h e requirements for t h e degree of Doctor of tion. Repeated recrystallization from ligroin yielded 3 .O Philosophy, 1952. g. (59%) of cream-colored plates, m.p. 48-33'. An xu( 2 ) Presented in p a r t before the Fifth Annual hleetinpin-miniature thentic sample, supplied by T. Nozoe melted 49-51', A of t h e Philadelphia Section of T h e American Chemical Society, Janumixture of the samples melted 48-50'. ary 29, 1953. Titrations were performed as described previously4 with (3) Public Health Service Research Fellow of the National Institutes the exception t h a t i t was generally found necessary to evaluof Health, 1953-1954. ate the first formation constants of the Be, P b and Zn com(4) B. E. Bryant, W. C. Fernelius a n d B. E. Douglas, THISJOURNAL, plexes by a modified procedure. In the presence of excess 7 6 , 3784 (1953). chelating agents it was found that coordination was so f a r
no depression with yohinibinc, 4' (c 1.26 in ethanol), [ C Y ] ~ f'i6 ~D 4 ' (c 1.18 in pyridine). Anal. Calcd. for CzlH26S20d: C, 71.17; H, 7.40; N, 7.91; OCH3, 8.75. Found: C, 70.92; H,7.5s; N, 7.92; OCH3, 111.1). 234-23(i0, [aIz2D
*
+ 47
=k
( 5 ) E. P. Kohler, A I , Tishler, H. Potter a n d H. T. Thomson, ibid., 61, 1057 (1030).
(6) A . P. Giraitis a n d J . I.. Bullock, ibid., 69, '351 (1037)
1697
NOTES
Mar. 20, 1954
TABLE I 7
Compound
PKD
n
Be++
Pb++
Zn++
a-Methyltropolone
9.37
10.3 9.0
9.4 6.7
8.6 7.1
6-Methyltropolone
8.69
9.4 7.7
9.6 6.6
a-Isopropyltropolone
9.75
10.7 9.1
9.5 7.5
8.4 6.8 3.6 8.7 7.5
6-Isopropyltropolone
8.70
9.1 7.5
9.0 6.7
a-lsopropyltropolone
8.7
1 2 3 1 2 3 1 2 3 1 2 3 1 2
Tropolone
8.12
Acetylacetone
9.70
3 1
2 1 2
8.4 7.0 9.0 7.7
8.7 7.0 3.6
log K f n
a++
Ni++
eo++
ME++
8.4 6.7 3.7 8.4 6.6 4.1 8.6 6.9 3.7 8.5 6.5 4.0 8.4 6.5 3.9 7.7 6.1 6.9
8.0 6.3
6.0 4.6 2.6 6 .0 4.6 3.1
5.1 3.4
8.1 6.7
6.2 5.2
5.2 3.6
7.9 6.3 3.8
6.2 4.8 3.0
5.4 3.6
7.9 6.2
5.3 3.6
5.1
advanced t h a t E was equal t o one or greater before the addition of base. To obtain values in the region of E , = 0.5, solutions containing two moles of metal ion permole of chelating agent were titrated. I n these cases, constants were not calculated from formation curves, but by the method of Block and McIntyre.? Attempts to titrate a n excess of a-isopropyltropolone in the presence of Be ion led to the precipitation of yellow plates, m.p. 177". Anal. Calcd. for Be(CloHllOz),: C, 71.64; H,6.57. Found: C, 71.36; H , 6.34. Addition of a solution of Pb( N03)z to a-isopropyltropolone in 50% d F n e caused precipitation of light yellow plates, m . p . 164 . Anal. Calcd. for Pb(ClaHnOz)z: C, 45.03; H, 4.13. Found: C, 45.44; H , 4.12. The Ni and Be complexes of p-isopropyl-y-(3-methylbut2-enyl)-tropolone were found to be too insoluble for study by this method.
usually high contribution to stability due to the favorable size of the five-membered chelate ring. 3. Due to the unfavorable oxygen-oxygen distance in tropolonee the weak hydrogen bond causes tropolone to act as an unusually strong acid. Professor M. Calvin'O has suggested that the unusual character of these plots is best explained on the basis of the unusually high acidity of the tropolones rather than an unusual stability of these complexes. It is interesting to observe that the behaviors of the two smallest ions studied (H+ and Be++) are markedly similar; ;.e., the a-ions are bound more strongly than the /3-substituted ions. For ions larger than Be++, however, only minor differences are noted between the CY- and p-cornDiscussion pounds. The values determined are shown in Table I. The effects of hydrogen bonding and the size I n a previous publication,4 i t was pointed out that of the chelate ring on the nature of plots of log Kr the copper tropolonate was more stable than vs. ~ K are D being investigated further. copper derivatives of P-diketones of comparable Acknowledgment.-Most of the work reported acidity. Included in Table I are the values of the here was supported by the United States Atomic Be and Ni derivatives of acetylacetone. If the Energy Commission through contract AT(30-1)values of the first or second formation constants 907. We wish also to acknowledge the technical of the Ni or Be complexes are plotted vs. the PKD assistance of Mrs. Lillian Berg in a portion of the values of the respective chelating agents i t is found synthetic work reported here. that the complexes of tropolone and its derivatives (9) J. M. Robertson, J . Chem. SOL.,1222 (1951). group themselves about a single straight line, while (10) M.Calvin, private communication. the acetylacetone derivative of the metal ion in OF CHEMISTRY question is considerably (ca. 1.5 log units) removed DEPARTMENT PENNSYLVANIA STATE UNIVERSITY from the line for the tropolone derivatives. Again STATE COLLEGE,PENNSYLVANIA i t is seen that the tropolone complexes are more stable than those of P-diketones of comparable acidity. Extensions of the Tollens Condensation Calvin and Wilsons have postulated that resoBY 0. C. DERMERAND PAULW. SOLOMON nance within the chelate ring may considerably enhance the stabilities of compounds such as 12, 1953 RECEIVEDDECEMBER these. The unusual nature of the plots of log Kt The hydroxymethylation and subsequent reducvs. ~ K for D the tropolone complexes suggests several tion of carbonyl compounds containing active hypossibilities : 1. Resonance energy of the tropolone complexes is unusually high. 2. There is an un- drogen atoms by means of formaldehyde and calcium or sodium hydroxide' has been applied to some (7) B. P. Block and G. H.McIntyre, Jr., TAIS JOURNAL, 75, 5667 monosubstituted acetaldehydes, YCH&HO, to (1953). (8) hI. Calvin and K. Wilson, {bid., 67,2003 (1945).
(1) B. Tollens and P. Wiegand, A n n . , 268, 316 (1891).
